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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Surgery today 26 (1996), S. 250-257 
    ISSN: 1436-2813
    Schlagwort(e): breast cancer ; serum tumor marker ; carcinoembryonic antigen ; CA 15-3 ; tissue polypeptide antigen
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Serum carcinoembryonic antigens (CEA), CA 15-3, and tissue polypeptide antigens (TPA) have been used in monitoring the clinical course of patients with breast cancer. However, recent reports have suggested that the serial levels of these markers during therapy do not always correlate with the response to therapy. To clarify the usefulness of the serial combination assay of these markers in monitoring the clinical course of patients during therapy, we investigated the relationship between the initial changes and the kinetic patterns of the markers after therapy and the objective responses. When an increase or decrease of over 20% in these markers is taken to be significant, then the initial changes in all three markers significantly correlated with the therapeutic responses (P〈0.01). Five distinct kinetic patterns in the marker levels were observed. A paradoxical kinetic pattern of CEA and CA 15-3 levels — that is, an “initial surge and subsequent drop” — was seen in one-third of the responders. The TPA levels tended to exhibit a “steady decline” pattern in those responders. The sensitivity and specificity of the kinetic patterns to predict the clinical courses were significantly higher than those obtained from the analysis of initial changes. These findings thus suggest that adequate knowledge of the unique kinetics of each marker may help to make a more accurate prediction of the therapeutic responses.
    Materialart: Digitale Medien
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  • 2
    ISSN: 1436-2813
    Schlagwort(e): Adriamycin ; breast cancer ; c-erbB-2 ; immunoconjugate ; targeting therapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Adriamycin (ADM) was chemically conjugated to a murine monoclonal antibody, A0011, which recognizes the c-erbB-2 product, via a disulfide bond using N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-iminothiolane (2-IT). The molar ratio of ADM to the monoclonal antibody ranged from 15:1 to 25:1 and enzyme-linked immunosorbent assay (ELISA) showed that the binding activity of the conjugate was almost retained. We compared the efficacy of A0011 alone, ADM alone, the A0011-ADM conjugate, and a nonspecific murine IgM-ADM conjugate, against the human breast cancer cell lines SK-BR-3, MDA-MB-361, MCF-7, and BT-20. The A0011-ADM conjugate was observed to be ten times more cytotoxic to the cell lines overexpressing the c-erbB-2 product, namely, SK-BR-3 and MDA-MB-361, than free ADM, but it showed weak cytotoxicity against the cell lines with a low level of c-erbB-2 product expression, namely, MCF-7 and BT-20. However, free A0011 and nonspecific murine IgM-ADM conjugate showed no cytotoxicity toward any of the four cell lines, while the addition of a tenfold molar excess of A0011 inhibited conjugate cytotoxicity. These data suggest that conjugate cytotoxicity is antibody-mediated. Moreover, conjugate cytotoxicity at 10−6M was correlated with antigen volume, and the data were fitted to the regression equation y=−11.63logX+116.38 where the correlation coefficient =0.950. Our results indicate that targeting therapy aiming at the c-erbB-2 product may be useful in the treatment of breast cancers overexpressing the c-erbB-2 product.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1437-7772
    Schlagwort(e): bisphosphonate ; bone metastasis ; breast cancer ; osteoclast activity ; bone scintigraphy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background Bisphosphonates are powerful inhibitors of osteoclast-mediated bone resorption. They are effective in the treatment of Paget's disease of the bone, tumor-associated hypercalcemia, and osteoporosis. They are also used to treat metastatic bone disease. YM-175 is a new highly potent bisphosphonate. Bisphosphonates are also used as radiopharmaceuticals in bone scintigraphy. The data remain unclear as to whether or not the administration of large amounts of bisphosphonate interferes with the bone scintigraphy process. Methods We have treated 8 patients with bone metastases from breast cancer with 10 mg IV, once a week for 5 weeks. The monitoring of bone pain, laboratory analysis with bone metabolic markers, and bone imaging including x-ray and bone scintigraphy, was performed for 8 weeks. A quantitative method was employed to evaluate serial bone scintigraphy. Results Bone pain improved in 5 out of 8 cases at 2 and 4 weeks post-treatment without serious adverse effects, but the duration of pain relief was short. Markers of osteoclast activity were decreased significantly to a minimum at 2 weeks. No significant changes were shown in markers of osteoblast activity or in serum calcium levels. Intact parathyroid hormone (PTH) was elevated at 2 and 4 weeks. It appears that YM-175 suppressed osteoclast activity, however, its effect was negated by a PTH elevation response. No changes were detected in either x-ray findings or serial bone scintigraphy by use of visual images and quantitative methods. Conclusion YM-175, a new bisphosphonate, was a safe and promising drug for the treatment of metastatic bone pain from breast cancer. Osteoclast activity was suppressed by bisphosphonate treatment, but, the PTH response negated the osteoclast suppression. Furthermore, YM-175 treatment did not alter bone scintigraphic images.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1437-7772
    Schlagwort(e): breast cancer ; breast conserving therapy ; radiation therapy ; local recurrence ; boost irradiation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background Because of previously reported shortened follow-up periods, breast conserving therapy is still not prevalent for patients with breast cancer in Japan. This is a report of clinical trial results. Methods Between November 1987 and October 1995, breast carcinomas in 462 patients were treated with breast conserving therapy (BCT). Three hundred and sixty-four patients with follow-up periods of longer than 1 year, excluding simultaneous bilateral breast carcinomas, were analyzed. There were 19 stage 0,211 stage I, 132 stage II, and 2 stage III tumors according to the 1987 UICC classification. A total dose of 50 Gy was delivered over 5 weeks to the preserved breast using60Co γrays. The primary site was boosted with a total dose of 10 Gy in 5 fractions in 40 of the 83 patients whose tumor margins were either positive or close. Results In a follow-up period of 12 to 96 months with a median of 35 months, 8 patients developed a breast recurrence. The actuarial overall, relapse-free, and breast-recurrence-free survival at 5 years were 99.0%, 92.3%, and 97.8%, respectively. The difference in the local control rate was significant between patients with negative margins and those with positive margins (P〈0.0001), and between the patients with negative margins and those with close margins (P=0.0284). Conclusions The 5-year results of our trial were similar to those of other reported series. Positive and close margins are risk factors for breast recurrence. Improvements in optimal methods of radiation therapy including boost irradiation are needed.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    The protein journal 15 (1996), S. 273-279 
    ISSN: 1573-4943
    Schlagwort(e): Malic enzyme ; breast cancer ; nucleotide sequence ; expression
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract A cDNA coding for human breast cancer cell cytosolic NADP+-dependent malic enzyme was obtained. This cDNA is composed of a length of 2084 base pairs, with 1698 base pairs coding for 565 amino acid residues and a length of 386 base pairs representing a 3′-noncoding region. Comparing this nucleotide sequence with that from the normal human tissue [Loeber, G., Dworkin, M. B., Infante, A., and Ahorn, H. (1994),FEBS Lett. 344, 181–186] reveals that three nucleotides in the open reading frame and the length of 3′-noncoding region of the cDNA are different. One of the changes results in a substitution of serine at position 438 for proline, which, however, may not cause significant changes in the predicted secondary structure. A partial cDNA lacking the first 84 nucleotides in the open reading frame was successfully cloned and expressed functionally inEscherichia coli cells. ItsK m value forl-malate (1.21±0.11 mM) is four times higher than that for the natural human breast cancer cell malic enzyme (0.29±0.04 mM) but similar to that for the full-length recombinant enzyme (1.06±0.07 mM). TheK m values for Mn2+ and NADP+ (0.26±0.03 and 0.97±0.4μM, respectively) are similar to those for the natural enzyme (0.12±0.02 and 1.9±0.3μM, respectively) or the recombinant wild-type enzyme (0.56±0.04 and 0.44±0.02μM, respectively). A recombinant pigeon liver malic enzyme without the first 13 amino acid residues was used for comparison. TheK m values forl-malate and Mn2+ of the truncated enzyme (11.2±0.9 mM and 61.2±4.6μM, respectively) are over 40 times larger than those for the natural pigeon liver malic enzyme (0.21±0.02 mM and 1.06±0.08μM, respectively) or the recombinant wild-type enzyme (0.25±0.01 mM and 1.48±0.05μM, respectively). We suggest that the N-terminus of malic enzyme may be required for the substrate binding during the catalytic cycle.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1573-7276
    Schlagwort(e): activation ratio ; activity ; breast cancer ; MMP-2
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The proteolytic processes are thought to be the critical point in tumor invasion and metastasis, mainly by matrix metalloproteinases (MMPs) and serine proteases. We measured the activity of MMP-2 from 28 normal, 12 benign and 126 breast cancer tissues using gelatin zymography. Inactive MMP-2 (72 kD) was expressed in 53.6% of the normal and 66.6% of the cancer tissues, respectively (P= 0.77), while active MMP-2 (62 kD) was expressed in 28.6% and 73.0%, respectively (P = 0.003). The enzymatic activity of active MMP-2 (62 kD) measured in the gel band area was 4.0 ± 7.2 mm2 in normal breasts, 7.7 ± 9.8 mm2 in benign breast diseases, 9.5 ± 8.5 mm2 in ductal carcinoma in situ (DCIS), and 12.0 ± 13.7 mm2 in invasive cancers. The MMP-2 activation ratio (62 kD/62 kD + 72 kD) was 0.12 ± 0.18 in normal tissues, 0.10 ± 0.20 in benign diseases, 0.61 ± 0.22 in DCIS, and 0.50 ± 0.28 in invasive cancers. In conclusion, MMP-2 activation was the main cause of the increased 62 kD MMP-2 activity during the early phase of breast cancer, while production of MMP-2 supplemented the increased 62 kD activity in the late phase. We suggest, therefore, that these differential expressions of MMP-2 activation and production during the different stages of breast cancer progression are potential therapeutic targets for biological or gene therapy under the concept of stage-oriented cancer treatment.[⇃]
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    Cancer causes & control 7 (1996), S. 56-68 
    ISSN: 1573-7225
    Schlagwort(e): Aleohol ; body size ; breast cancer ; caffeine ; diet ; epidemiology ; review ; vitamins
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Epidemiologic evidence on the relation between nutrition and breast cancer is reviewed. After several decades of study, many aspects of the role of diet in breast cancer etiology are still unclear. Results from large prospective studies do not support the concept developed from animal and ecologic evidence that dietary fat intake in mid-life is associated with breast cancer risk. Thus, if fat intake is relevant to breast cancer, it is probably only at extremely low fat intakes or during early life. An emerging hypothesis that higher energy intake and growth rate in childhood and adolescence increases risk deserves further study. The possibility that diets rich in olive oil may be protective is also intriguing. Considerable evidence suggests that low intake of vegetables modestly increases the risk of breast cancer; however, the nutrients responsible remain elusive. The positive relation of alcohol intake with breast cancer risk has been seen repeatedly, and recently has been buttressed by studies showing that moderate alcohol intake increases estrogen endogenous levels. Advice to increase vegetable intake and limit alcohol consumption would probably have a modest, at best, effect on breast cancer risk. Future studies of the relation of nutrition during early life to subsequent breast cancer risk are needed.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Journal of thrombosis and thrombolysis 3 (1996), S. 13-21 
    ISSN: 1573-742X
    Schlagwort(e): postmenopausal ; hormone replacement therapy ; coronary heart disease ; breast cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Coronary heart disease is the leading cause of death in women in the United States and increases dramatically in postmenopausal women. The following review summarizes the known benefits and risks of hormone replacement therapy and gives recommendations for use of hormone replacement in women. Estrogen may play a role in preventing the development of atherosclerosis in women by raising levels of HDL cholesterol, lowering levels of LDL cholesterol and lipoprotein (a), lowering levels of fibrinogen and plasminogen activator inhibitor-1, dilating coronary arteries, preventing the oxidation of LDL cholesterol, decreasing the proliferation and migration of smooth muscle cells, and decreasing the production of inflammatory cell activators. These anti-atherogenic effects of estrogen may translate into clinical benefits. A meta-analysis of 31 studies yielded a 44% reduction in the risk of coronary heart disease in women taking estrogen alone. Unopposed estrogen is associated with an increased risk of endometrial cancer; therefore, progestin is added to estrogen in women with an intact uterus. Less is known about the effect of the combination of estrogen and a progestin on the risk of coronary heart disease. Estrogen is also beneficial in the prevention of osteoporosis; however, long-term use of estrogen alone and estrogen in combination with progestin may increase the risk for breast cancer. Mathematical modeling predicted that women with no risk for cardiovascular disease, cancer, or osteoporosis may gain 0.9 years of life with the use of estrogen alone; women with risk factors for cardiovascular disease can expect to gain 1.5 years of life; and women with coronary heart disease at the age of 50 can expect to gain 2.1 years of life. The current American College of Physicians recommendations for hormone replacement are as follows: (1) All women should be considered; (2) women with a hysterectomy should receive estrogen alone; (3) women at risk for, or with, coronary heart disease are most likely to benefit from estrogen; with an intact uterus, progestin must be added; (4) risks of estrogen may outweigh benefits in women at increased risk for breast cancer. Definitive guidelines for the treatment of women must await the results of randomized clinical trials in the ongoing Women's Health Initiative. These will not be available for several years, and until then any recommendations for women will have to be judged from estimates of risk rather than of benefit from reduction of risk. The decision whether to initiate estrogen replacement in postmenopausal women is one that still needs to be made on an individual patient basis.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    Journal of mammary gland biology and neoplasia 1 (1996), S. 381-389 
    ISSN: 1573-7039
    Schlagwort(e): Anti-estrogens ; breast cancer ; TGFβ ; autocrine ; paracrine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Transforming growth factor β (TGFβ) has potent inhibitory effects upon epithelial proliferation and malignant progression may be associated with breakdown of the autocrine and paracrine inhibitory loops in which TGFβ participates. The therapeutic effects of anti-estrogens may be partially attributable to boosting of local endogenous levels of TGFβ. This article reviews the evidence in support of TGFβ being a proximate effector in mediation of the anti-neoplastic effects of anti-estrogens. Both the conventional estrogen receptor (ER)3 dependent and ER independent mechanisms of action are likely to be involved. Evidence for preferential stromal induction of TGFβ by anti-estrogens is emphasized, together with the therapeutic potential of this strategy for improving outcome in early breast cancer irrespective of ER status.
    Materialart: Digitale Medien
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 37 (1996), S. 169-178 
    ISSN: 1573-7217
    Schlagwort(e): breast luteal heat cycle ; breast cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Wearing a special thermometric brassiere, selected women self-measured their breast surface temperature. These measurements were made during one hour each evening at home for one menstrual cycle under standard conditions of overclothing and room temperature. To stage their cycle they also collected daily samples of saliva in their freezer for immuno-assay of progesterone concentration in the laboratory. A total of 82 women participated, most having young families. This total included four groups, a control group (N = 25) and three ‘disease’ groups, namely: family history of breast cancer (14); benign breast disease (12); and a ‘cancer-associated’ group (31) who had had previous cancer surgery. A significant breast temperature rhythm with a period at or about 28 days was found not only in the controls but also in the three groups of breasts designated ‘disease’. Nevertheless, consistent rhythm abnormalities were found in all the disease groups. Most evident was a hyperthermia throughout the cycle, a reduction in the rhythm amplitude, and a tendency for the breast temperature rhythm to be manifest 1–2 days earlier in the menstrual cycle.
    Materialart: Digitale Medien
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  • 11
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 37 (1996), S. 197-207 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; incidence trends ; birth cohort ; risk factors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Using a log-linear model, we examined the 59-year incidence trends (1932–1990) of breast cancer by age, sex, and birth cohort in Saskatchewan, Canada. The incidence of breast cancer showed a continuously increasing trend since the 1930s. The trend was age dependent — in general, the 60 years and older age group had greater increases in incidence rates than did younger age groups. The increase in incidence rates in the 45 years and older age group was consistent over time and the incidence rates for those younger than 45 years increased until the 1960s, with a decline in trend following the 1960s. Birth cohort was a significant factor in the incidence of breast cancer. The major birth cohort effect can be described for those born from 1852 to 1927 — in every age group breast cancer incidence increased as the birth years advanced. For those born after 1927, the incidence of breast cancer was unchanged as the birth cohort changed and was sustained at a high level. Whether this phenomenon suggests that the risk factors for breast cancer ceased to increase over time needs to be confirmed by further studies.
    Materialart: Digitale Medien
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  • 12
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; prognostic factor ; erbB2 ; immunoenzymatic assays ; immunohistochemistry ; Western blotting
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Four different methods to measure in parallel the erbB2 protein expression (p185neu) were evaluated in order to: a) compare two enzyme immunoassays with the immunohistochemical assays (IHC) and western blotting (WB) and b) extrapolate eventual relationships between erbB2 and biological parameters. Tissue samples from 248 patients with primary breast cancer were consecutively assayed. We used two different cut-off levels for WB, ELISA, and EIA, defined as follows: 1) the highest level of expression of non malignant tissue was chosen as the discriminant threshold between ‘low’ and ‘elevated’ samples: 2) the elevated group was further subdivided into two subgroups: ‘intermediate’ and ‘high’, according to their median value. According to the first cut-off, the results were considered ‘elevated’ in about 52% of cases with the three biochemical methods, while using the second cut-off the percentage lowered to about 26%. Considering this cut-off, the concordance rates between the paired biochemical methods ranged between: 78.4% (WB vs EIA), 93% (ELISA vs EIA), and 82.6% (ELISA vs WB). The comparison between biochemical and immunohistochemical methods gave these concordance rates: 82% (WB vs IHC), 90.5% (ELISA vs IHC), and 85.5% (EIA vs. IHC). According to the first cut off level, 27.5% of tumor samples showed IHC detectable p185 levels, in agreement with other immunohistochemical studies. The relationship between high erbB2 and estrogen and progesterone receptors showed an inverse association. No relationship was found between erbB2 and axillary lymph node positivity or tumor size. In short, the results of the four methods seem generally well correlated; nevertheless, it appears that different methodological approaches of measuring p185neu are not completely equivalent, and there is a need for an authoritative standardization and quality control for clinical applications.
    Materialart: Digitale Medien
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  • 13
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 37 (1996), S. 277-289 
    ISSN: 1573-7217
    Schlagwort(e): autologous stem cells ; breast cancer ; high-dose chemotherapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Background Because metastatic breast cancer is a lethal disease despite some responsiveness to systemic chemotherapy, high-dose chemotherapy with autologous stem cell rescue is being utilized with increasing frequency. This analysis was undertaken to determine the outcome for such patients treated with intensive chemotherapy between 1989–1994, at the Hoag Cancer Center in Newport Beach, CA. Methods During 1989, only patients with metastatic disease who had failed more than two standard breast cancer chemotherapy regimens were considered eligible for such treatment. They received high-dose BCNU/ cyclophosphamide/cisplatinum chemotherapy with autologous bone marrow rescue. After January 1990, patients with metastatic disease were eligible only if they had received limited prior chemotherapy and demonstrated responsiveness to induction chemotherapy. Beginning June 1990, patients with metastatic disease were to receive mitoxantrone and thiotepa (MiTepa) followed by peripheral blood stem cell rescue, then ifosfamide, carboplatin and etoposide (ICE) chemotherapy followed by peripheral blood stem cell rescue. High-risk adjuvant patients were to receive one course of ICE followed by rescue. Results Between 1/89–12/94, 48 breast cancer patients underwent 65 intensive chemotherapy treatments followed by autologous stem cell rescue. During 1989, three of the eight patients with metastatic disease died within 60 days because of therapy-related complications. The longest failure-free survival (FFS) of these eight was 12.2 months, and the longest overall survival (OS) 20.5 months. Since 1/90, one physician has treated 24 patients with metastatic breast cancer, 17 of whom actually underwent two successive transplants with MiTepa/ICE. For the latter group, median FFS is 23.2 months; median OS is 39.7 months. There were no acute deaths, but two patients died 〉 60 days after initial transplant from therapy-related complications, venoocclusive disease (5.2 months) and myelodysplastic syndrome (30.5 months), while five died of progressive disease at 22.5, 32.8, 39.4, 46.3, and 51.3 months. For the 24 metastatic patients treated 1990–1994, 1-, 2-, and 3-year FFS rates are 86%, 40%, and 17%, respectively, while OS rates are 91%, 80%, and 65%. Of 11 patients treated in the adjuvant setting, only one has relapsed (9.8 months) with follow-up from 3–61 months. Conclusions Modifications made in the program, including selection of patients responsive to induction chemotherapy, transfusion of peripheral blood stem cells, implementation of hematopoietic colony stimulating factors, and use of tandem intensive treatments has been associated with a low rate of acute morbidity and encouraging survival rates.
    Materialart: Digitale Medien
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  • 14
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 38 (1996), S. 3-9 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; cancer treatment ; colon cancer ; Pseudomonas exotoxin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Pseudomonas exotoxin has been genetically modified so that it targets cancer cells. This was accomplished by deleting its cell binding domain and replacing it with Fv fragments of antibodies that react with breast, colon, and other cancers. Several recombinant immunotoxins are now in clinical trials.
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 38 (1996), S. 145-151 
    ISSN: 1573-7217
    Schlagwort(e): trefoil proteins ; breast cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Trefoil proteins form a specific group of stable secreted polypeptides. They are expressed in a lot of human cancers and during inflammatory processes of the gastrointestinal tract. Recently a new human trefoil protein, ITF/hP1.B, was isolated. Until now no studies of the activity of this gene in human solid tumors exist. In our examination we show for the first time that this gene is transcribed in human breast cancer. In contrast to another trefoil protein, pS2, the expression of ITF/hP1.B is not under control of estrogen in the human breast cancer cell line MCF-7. We suggest that the gene activity of ITF/hP1.B in addition to pS2 expression may be an improved prognostic marker in human breast cancer.
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  • 16
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 38 (1996), S. 183-199 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; quality of life ; rehabilitation ; sexual functioning
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose To describe the psychosocial concerns and quality of life of breast cancer survivors evaluated 2 and 3 years after primary treatment. Methods A sample of 139 breast cancer survivors who had been interviewed during the first year after primary treatment participated in a mailed survey at 2 years (N = 69) and 3 years (N = 70) after initial surgery. A random sample of these survivors were also interviewed in person. The mailed questionnaire included standardized instruments to assess quality of life (QL), rehabilitation needs, and psychological distress. Additional survey questions were developed to examine post-surgical recovery, employment and insurance problems. social support, and existential concerns. The in-person interviews expanded on these questions and systematically compared these patients' rehabilitation needs to those which existed at the time of an interview 1 year after surgery. Results The 2 and 3 year participants in this follow-up study did not differ from each other on their prior assessments with standardized QL instruments during the first year after surgery, nor did they differ from the full study sample of 227 women. The scores on the Profile of Mood States and the Functional Living Index-Cancer were the same for the 2 and 3 year survivor groups and did not differ from the previous assessments at 1 year after initial treatment. The scores on the Cancer Rehabilitation Evaluation System showed a significant decline in Global Quality of Life, Sexual Functioning and Marital Functioning between the 1 year and 3 year evaluations. For the 2 year sample only Sexual Functioning showed a deterioration between the 1 and 2 year evaluations. Using the RAND 36-Item Health Survey 1.0, the breast cancer survivors were compared with patients from the Medical Outcomes Study. The breast cancer survivors demonstrated higher levels of functioning in many dimensions (role functioning, social functioning, pain, and general health) than the patients with chronic medical conditions. In spite of relatively good physical and emotional functioning on this generic measure of health status and quality of life, these breast cancer survivors reported a number of important and severe rehabilitation problems that persisted beyond one year after primary treatment. Especially frequent were problems associated with physical and recreational activities, body image, sexual interest, sexual function, and problems with dating for those who were single. Conclusions Breast cancer survivors appear to attain maximum recovery from the physical and psychological trauma of cancer treatment by one year after surgery. A number of aspects of QL and rehabilitation problems worsen after that time. Nevertheless, breast cancer survivors rate their QL more favorably than outpatients with other common medical conditions, and they identify many positive aspects from the cancer experience.
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  • 17
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 39 (1996), S. 1-6 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; animal models ; rodent models ; in vivo studies
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Animal models of breast cancer have been widely used to study various aspects of breast cancer biology, and are remarkably diverse, encompassing chemically and virally induced tumors, human tumor xenografts, and transgenic mouse models. Several novel models have become available during the past few years, including tumors induced by polyomavirus and adenovirus, and a series of human cell line variants. The several following articles describe, in some detail, the characteristics of these models and their relevance to the human disease. Descriptions of each of the major models,e.g., 7,12-dimethylbenz(a)anthracene-induced, MMTV-associated, and human breast cancer cell line xenografts, also are included. The limitations and advantages of several of these models, and some issues relating to the choice of models, are briefly discussed in this overview.
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  • 18
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; β1–6 branched oligosaccharides ; carcinoembryonic antigen ; L-PHA lectin ; 3-D cell culture
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Expression of β1–6 branched oligosaccharides in human breast cancer cells was investigatedin vivo andin vitro. Lectin histochemical and lectin blotting analyses of surgically resected specimens were performed using L-PHA (phaseolus vulgaris leukoagglutinin) lectin, which binds to β1–6 oligosaccharides. The glycoproteins bearing β1–6 oligosaccharides of breast cancer tissues were found to be 170 kD and 120 kD in molecular weight, and the former appeared to be an epitope of carcinoembryonic antigen (CEA). The β1–6 oligosaccharides were expressed in both cancer cell lines at the outer layer of the colonies when cultured in type I collagen, but not in agarose gel. No correlation was observed between β1–6 expression and cell cycle. The β1–6 oligosaccharides did not coincide with breast cancer-associated antigens, such as CEA, MUC1, and cathepsin D. The β1–6 oligosaccharides of these cell lines were markedly inhibited when swainsonine, a mannosidase II inhibitor, was added to the culture medium. The 120 kD molecule, which was obtained from MCF-7 cells cultured in type I collagen gel, was consistent with that of breast cancer tissues and was similar to lysosome-associated membrane glycoproteins (LAMPs). The results suggest that the glycoproteins bearing β1–6 branched oligosaccharides in human breast cancer incorporate an epitope of CEA and human LAMPs and that the expression of LAMPs may depend on their surrounding matrices and may play an important role in cancer invasion or metastasis.
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  • 19
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 39 (1996), S. 93-102 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; metastasis ; nude mice ; orthotopic injections
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Immunodeficient animals, principally nude mice, when used in appropriately designed studies have been shown to be useful for the experimental analysis of human breast cancer metastasis. As with many other human tumors, the implantation of breast cancer cells into an anatomically appropriate tissue (the mammary fatpad) results in increased tumor take and incidence of metastasis for certain cell lines compared with subcutaneous injection. Testing a number of widely available human breast cancer cell lines identified the MDA-MB-435 cell line as the most metastatic, producing lung and lymph node metastases in a high proportion of nude and severe combined immunodeficient (SCID) mice after injection in the mammary fatpad. Mixing human breast cancer cells with normal fibroblasts or with Matrigel also increases the tumor incidence and growth rates in nude mice. Different routes of injection can be used to assess the ability of human breast cancer cells to form metastatic lesions in the lungs (i.v. injection), the liver (injection in the spleen), the brain (direct or intracarotid artery injection) and the bone marrow and bone (injection into the left ventricle of the heart). These different approaches demonstrate the potential of experimental studies of human breast cancer growth and metastasis using immunodeficient mice; this model is valuable for experiments that test the role of metastasis-associated genes and the efficacy of novel forms of therapy.
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  • 20
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; mitoxantrone ; anthracyclines ; randomized trial ; alopecia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Background: Drug selection for the treatment of advanced breast cancer is based on both efficacy and toxicity. Combination chemotherapy produces higher response rates than single agents, of which doxorubicin is the most active. This study compares efficacy and toxicity of the drugs doxorubicin and mitoxantrone when used as part of a 3 drug combination. Doxorubicin is the most active agent, but also one of the most toxic, and in this study was compared, in a 3-drug combination, with mitoxantrone with the aim of achieving comparable efficancy with reduced toxicity. Patients and methods: 110 patients with advanced breast cancer previously untreated by chemotherapy were randomized to receive cyclophosphamide and vincristine, together with either doxorubicin 50 mg/m2 IV (VAC) or mitoxantrone 10 mg/m2 (VNC) for up to 6 cycles. Results: Of 53 eligible patients randomized to VAC, the overall response rate was 55% (CR rate 17%), while of 55 patients randomized to VNC the overall response rate was 42% (CR rate 7%). The difference is not statistically significant (p = 0.07), but there was a trend towards a higher response rate to VAC in patients aged less than 60, those with nodal and soft tissue disease, and those with 2 or more sites of disease. The principal difference in toxicity was reduced alopecia in favour of VNC. However there was also an increased number of deaths within the first cycle in patients randomized to VAC. There were no differences in survival, relapse free interval, or freedom from progression between the two arms. Conclusions: Both VAC and VNC are effective regimens in advanced breast cancer. While the confidence limits in this study mean the response rate advantages of VAC could have arisen by chance, younger patients with adverse prognostic factors may warrant consideration of the VAC regimen.
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  • 21
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; fine needle aspirate cell ; human papillomavirus ; PCR ; Southern blot hybridization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Oncogenic human papillomavirus (HPV) types 16 and 18 commonly associated with cervical cancer are found in many epithelial malignancies at extra-genital sites including breast. The transforming gene products of HPV have also been shown to immortalize breast epithelial cellsin vitro. But the findings of HPV DNA in breast carcinoma are found to be contradictory. In the present study fine needle aspirate cell (FNAC) samples from 26 breast cancer patients and four breast tumour biopsies were analysed for the presence of HPV 16 and 18 DNA sequences by both polymerase chain reaction (PCR) and Southern blot hybridization. Of 26 fine needle aspi rate cell samples and four breast cancer biopsies, not a single sample was found to be positive by either PCR or Southern blot hybridization. The observation of complete absence of HPV DNA sequences in breast cancer refute the possibility of any role for oncogenic genital HPV types 16 and 18 in the pathogenesis of breast cancer.
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  • 22
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; gene amplification ; c-erb-B2 ; fine-needle biopsies
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Prognostication of breast cancer patients, not operated at diagnosis, poses a clinically difficult problem. To use gene amplification we examined cytological samples and determined c-erb-B2 gene copy number with semiquantitative PCR. Control experiments showed the same gene-copy number in aliquots that were either air-dried (and MGG-stained), fixed in methanol (and air-dried), or snap-frozen in liquid nitrogen. Therefore we examined the prognostic value of c-erb-B2 amplification in 95 breast cancer patients that had not been operated at diagnosis (up to 12 years previously). Tumor cells were obtained from routine archival cytological smears. 15 patients (16%) had developed amplification. Univariate and multivariate analysis showed that c-erb-B2 amplification is a significant prognostic factor (p 〈 0.0001). Hence routine cytological MGG smears can be used for prognostic determination.
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  • 23
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; carcinogens ; cathepsin D ; cathepsin B ; cathepsin L ; c-Ha-ras oncogene ; invasion ; tumorigenicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract To investigate the regulation of lysosomal enzymes during carcinogenesis, we measured cathepsins (Cats) D, B, and L in MCF-10F, which is a human breast epithelial cell line, and cells evolved after treatment with carcinogen and transfected with c-Ha-ras oncogene. The clones used in this study, MCF-10FTras, D3, D3-1, and D3-1Tras, expressed no estrogen receptors and gradually increased invasive potential, while oncogenetransfected lines were also tumorigenic in SCID mice [16,19]. Cats D, B, and L were determined in the cells and in cell media using enzyme-linked immunosorbent assay (ELISA), specific enzyme activity measurements, and immunocytochemistry. The major intra- and extracellular lysosomal proteinase in these cells was Cat D (30–180 pm/mg), followed by Cat B (2–10 pm/mg) and Cat L (1–5 pm/mg). An inverse relationship between intracellular Cat D levels and invasive potential of carcinogen-treated and c-Ha-ras oncogene-transfected cell lines was observed. No significant changes in extracellular concentration of Cat D precursor in this series of cell lines was observed. Intracellular levels of Cats B and L were unchanged or slightly lower in carcinogentreated D3 and D3-1 cells, as well as in MCF-10FTras. On the other hand, in D3-1Tras cell line, evolving from c-Ha-ras transfected D3-1 line, 3.5 fold and 4.4 fold increases in Cat B and Cat L, respectively, but a 2 fold decrease in Cat D, were observed compared to the parental cell line. Immunocytochemical staining showed a granular, polarized perinuclear and cytoplasmic staining of cathepsins in all cell lines. Cysteine proteinases stained more frequently and more intensely in D3-1Tras compared to other lines, confirming the immunochemical assays. We hypothesize that several molecular events, caused by a carcinogen and an oncogene such as c-Ha-ras, are needed to increase Cat B and Cat L, but not Cat D, expression. Therefore, the cysteine and aspartic lysosomal proteinases are differentially expressed in the breast cell lines with more invasive phenotype.
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  • 24
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 39 (1996), S. 247-259 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; cell lines ; serum-free medium ; tissue culture
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Over a period of 6 1/2 years between January 1986 and May 1992, 135 unselected primary breast cancers were cultured and of these 10 developed into cell lines. Six of the lines grew in defined serum-free medium, while the other four required supplementation with 0.5% fetal calf serum. Two of the lines are from the same breast, being derived from a local excision specimen and from a mastectomy specimen 12 months later. In addition, 12 lymph nodes containing metastatic breast cancer were cultured; one of these cultures became permanent in a defined serum-free medium. Oestrogen receptor (ER) status was negative in all but one of the tumours which grew successfully, and even in this case the derived cell line is ER negative. The epithelial nature of the lines has been confirmed by immunocytochemistry and by electron microscopy (EM), while their malignant nature is shown by morphology, unattached growth, chromosome analysis, and, in the case of the line from a lymph node metastasis, the absence of any benign source of epithelial cells.
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  • 25
    ISSN: 1573-7217
    Schlagwort(e): CSF-1 ; serum markers ; breast cancer ; cytokines ; prognosis ; metastasis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Earlier results [1], suggesting an autocrine tumor cell stimulation by CSF-1, are in agreement with data by Fildermannet al. [2], showing an enhanced motility and invasiveness in the CSF-1 receptor expressing BT20 breast cancer cell line upon stimulation with recombinant CSF-1. Tumor-cell secreted CSF-1 has also been shown to cause monocyte recruitment, but not cytotoxicity [3]. Down-regulation of monocyte class II antigen expression after exposure to high concentrations of CSF-1 [4] may decrease macrophage-mediated tumor cytotoxicity and favor tolerance. Raised CSF-1 serum levels may thus increase tumor metastatic behavior as well as cause immune suppression in advanced stage disease. We set out to evaluate serum CSF-1 levels in primary and metastatic breast cancer. Serum samples from one hundred and eighteen primary breast cancer patients and seventy-five patients with metastatic disease were assayed by radio-immuno-assay (RIA) for circulating colony-stimulating factor 1. Mean serum levels were significantly higher in the metastatic population (9.7 ng/ml ± 0.8) as compared to the patients with primary tumors (4.2 ± 0.2) (p = 0.0001). Patients with early stage tumors (T0/T1/T2) had significantly lower levels than patients with tumors of larger size (T3/T4) (p = 0.0001). Relapse and survival statistics were analyzed using Kaplan-Meier estimates. Samples from 118 primary breast cancer patients were available to study. The median follow up was 85 months (range: 1–108). An elevated CSF-1 concentration (〉 6.6 ng/ml or 〉 550 Units/ml) was associated with a shorter disease free interval (p = 0.03). In a multivariate analysis, including T (clinical tumor size), N (clinical node status), histological grade, and hormone receptor status, CSF-1 remained significantly associated with a poorer outcome (relative risk of relapse: RR: 3.3 [1.3–8.5]), together with tumor size (RR: 2.8[1–8.2]) and clinically involved nodes (RR: 4.1[2.1–8]). These results were not modified following adjustment for type of treatment. We conclude that raised circulating CSF-1 levels may be an indicator of early metastatic relapse.
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  • 26
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; thrombosis ; hemostatic factors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Cancer is often associated with abnormal activation of coagulation leading to a prothrombotic state. Some chemotherapeutic agents used for cancer may induce thrombosis but their biological alterations in the hemostatic system are not yet well understood. This study evaluated alterations of coagulative and fibrinolytic parameters following chemotherapy. In plasma samples of 38 patients (median age: 49 years) receiving CMF (schedule 1–21 or 1–8) for Stage II breast cancer, we evaluated: PT, aPTT, antithrombin III (AT-III), protein C (PC), protein S (PS), thrombinantithrombin complex (TAT), prothrombin fragment F1 + 2 (F1 + 2), fibrinogen (Fbg), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI - 1) and D-dimer (D-D). PT, aPTT, and Fbg were determined with routine methods; AT-III, PC, and PS were measured with coagulative tests; PC and PS were also evaluated with immunoenzymatic methods. t-PA, PAI-1, D-D, TAT, and F 1 + 2 were measured with immunoenzymatic methods. All tests were performed immediately before starting therapy and after each cycle. A PC antigen decrease appeared soon after beginning therapy and lasted throughout chemotherapy. The lowest values were present after the first treatment both in the CMF 1–21 group (mean ± SD = 72.5 ± 10.8%) and in the CMF 1–8 group (mean ± SD = 77.2 ± 6.9%); PC activity was also decreased. PS antigen decreased after the first administration (mean ± SD = 73.3 ± 10% in CMF 1–21 group, and 72.5 ± 4.9% in CMF 1–8 group); PS activity also decreased. PAI-1 antigen levels increased (mean ± SD = 43.1 ± 20.4 ng/ml in the CMF 1–21 group, and 37.5 ± 12.2 ng/ml in CMF 1–8 group) lasting up to the last cycle. CMF provokes a trend toward hypercoagulability; this effect should be considered when chemotherapy is employed in advanced cancer patients at high risk for thrombosis, or in patients with other risk factors.
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  • 27
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; frozen section ; lymph node metastases
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The diagnostic value of intraoperative histologic examination of frozen sections of axillary lymph nodes was investigated in 243 patients with operable breast cancer. One to six hard or enlarged axillary nodes were sampled from the axillary pad which was derived from a partial axillary dissection (including level 1 and 2 nodes). Half of these nodes were histologically examined using frozen sections during surgery. After a total axillary dissection, both the axillary nodes in the partial axillary dissection and the nodes dissected at level 3 were histologically examined on permanent section. A mean of four nodes were sampled (range: 1 to 6). Axillary dissection yielded a mean of 22 nodes (range: 6 to 60). Axillary sampling detected the presence of metastases in 65 of 84 (77%) patients with positive axillary lymph nodes. In the patients in whom the axillary involvement was not identified by axillary sampling, however, the extent of axillary involvement was limited to levels 1 and 2. Therefore, a partial axillary dissection may be justified for patients in whom axillary involvement is not found on frozen section of nodes from axillary sampling, whereas a total axillary dissection should be performed for patients in whom axillary involvement is found by these procedures.
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  • 28
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 40 (1996), S. 243-249 
    ISSN: 1573-7217
    Schlagwort(e): argyrophilic cells ; androgen receptor ; breast cancer ; carcinoid ; chromogranin A ; estrogen receptor ; Grimelius silver stain ; progesterone receptor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Nine ‘carcinoids’ of the breast (argyrophilic carcinomas) were examined for the presence of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR), using immunohistochemistry. The tumours were selected on the basis of their histo-morphological appearance and positive Grimelius stain. All cases were immunoreactive for neuron-specific enolase (NSE). In one case the tumour cells were intensely chromogranin A positive. All cases were ER positive, while 5 cases expressed AR and 5 cases PR. Immunostaining for ER and simultaneous demonstration of argyrophilia or chromogranin A expression in chromogranin A positive argyrophilic carcinoid tumour of the breast provided further evidence that neuroendocrine cells in breast tumours express sex steroid receptors. The similarity in sex steroid receptor expression pattern in ‘carcinoids’ of the breast and the more common categories of breast cancer suggests an identical responsiveness to endocrine therapy.
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  • 29
    Digitale Medien
    Digitale Medien
    Springer
    Journal of mammary gland biology and neoplasia 1 (1996), S. 177-187 
    ISSN: 1573-7039
    Schlagwort(e): Protein kinase C ; breast cancer ; apoptosis ; substrates
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Protein kinase C (PKC) comprises a family of ubiquitously expressed phospholipid-dependent enzymes that regulate cell growth and differentiation. Several effectors that modify mammary cell biology work at least partially through PKC-dependent pathways. Studies with mammary epithelial cells and tissues have demonstrated probable roles for the PKCs in processes associated with carcinogenesis including proliferation, estrogen sensitivity, and apoptosis. The involvement of PKCs in this wide variety of responses may in part be explained by the expression of multiple PKCs in breast tissue and the possibility that individual PKCs selectively phosphorylate different proteins and preferentially mediate different biological responses. Further understanding of the role of individual PKCs in mammary cell growth and tumor promotion/progression is likely to lead to new insights for breast cancer diagnosis and treatment.
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  • 30
    Digitale Medien
    Digitale Medien
    Springer
    Journal of mammary gland biology and neoplasia 1 (1996), S. 199-206 
    ISSN: 1573-7039
    Schlagwort(e): ErbB receptors ; type I receptor tyrosine kinase ; EGF ; NDF ; mammary gland ; breast cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract One of the first consistent genetic alterations found in human breast tumors was amplification of theerbB-2 gene leading to overexpression of the protein. ErbB2 is a member of the ErbB/type I family of receptor tyrosine kinases which also includes epidermal growth factor receptor, ErbB3 and ErbB4. The role of ErbB2 in the biology of the mammary gland as well as in breast cancer development is under intense investigation. In clinical studies, the ErbB2 protein level has been examined for its utility in predicting patient prognosis and response to treatment. The ErbB2 receptor is also being tested as a target for tumor directed therapies.
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  • 31
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 38 (1996), S. 161-168 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; breast self-examination ; cancer control ; cancer survival
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary A prospective study was conducted to investigate the possible effect of breast self-examination (BSE) on cause-of-death-specific survival rate of breast cancer patients. Six hundred and four breast cancer patients diagnosed in 1984–1986 in Finland, and applying for breast prostheses, were interviewed about both their BSE practices prior to cancer diagnosis and the actual method of tumor detection. No clear differences were observed in the stage distribution or cause of death-specific five-year survival rates between individuals with different BSE practices. After adjustment for potential confounders in the Cox proportional hazards analysis, no differences in risk of breast cancer death were observed for those who performed BSE monthly as compared to those who practised BSE less frequently or not at all. When the method of detection was taken into account, it turned out that only 34 (7.6%) of the 448 regular BSE practisers had actually detected their cancers by means of BSE. Furthermore, no survival advantage was associated with detection of breast cancer by means of BSE. Those BSE practisers whose cancer was detected by BSE had a similar or slightly worse prognosis compared to BSE practisers whose cancer had been detected by other means. Our results suggest that BSE practice is not beneficial in terms of breast cancer survival, nor is detection of breast cancer by means of BSE. Conclusive evidence should, however, be obtained from prospective randomized studies of breast cancer mortality.
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  • 32
    ISSN: 1573-7217
    Schlagwort(e): AgNORs ; silver staining ; breast cancer ; tumor stage ; prognosis ; wet autoclave pretreatment
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Argyrophilic nucleolar organizer region associated proteins (AgNORs) are known to reflect cellular and nucleolar activity. Due to a novel staining procedure, which substantially improves visualisation of AgNORs on formalin-fixed and paraffin-embedded material, AgNORs can be reliably demonstrated as true substructures of the nucleoli. The aim of the present study was to apply a standardized morphometric AgNOR quantification on a large series of breast carcinomas with regard to its prognostic relevance. AgNOR quantity was evaluated on archival tumor tissues of 115 adenocarcinomas of the breast treated with the wet autoclave method prior to standardized silver-staining and morphometric analysis. AgNOR parameters were correlated to prognostic features (steroid hormonal receptor status, tumor type, tumor size, histological grading, pTNM, and UICC stage) carrying out both univariate and multivariate survival analyses. AgNOR number and area were proven to be statistically significantly related (Pearson correlation coefficient: 0.67, Bonferroni adjusted P = 0.0001). Almost all AgNOR parameters, in particular CV (coefficient of variation) of corrected area (δ-area) and CV of number, were statistically significantly correlated to estrogen and progesterone receptor status as well as histological grading of tumors. Increased AgNOR parameters were statistically significantly associated with early tumor relapse and cancer related death. Univariate and multivariate analysis by means of Cox regression revealed independent prognostic significance for CV of δ-area and number of AgNORs. Various AgNOR parameters (CV of number, CV of δ-area, CV of area, mean δ-area, and mean area of AgNORs per nucleus) determined on wet autoclave pre-treated formalin-fixed and paraffin-embedded breast cancer tissues are statistically highly significantly associated with the prognostic outcome, independently predicting tumor-free and overall survival.
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  • 33
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; tamoxifen ; interferon
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary It has been demonstrated, both in breast cancer cell lines and in metastatic breast cancer patients with cutaneous lesions that could be biopsied, that treatment with interferon beta (IFN-B) can increase expression of both estrogen (ER) and progesterone receptors (PgR). To evaluate the efficacy and toxicity of the combination of IFN and tamoxifen, 33 metastatic breast cancer patients were treated with the following regimen: IFN-B, 6.0 million units intramuscularly IU 3 times a week for two consecutive weeks followed by IFN-B 6.0 million IU im 3 times a week with concomitant tamoxifen 20 mg orally daily. Patients were pre and postmenopausal with median age of 60 years, median ECOG PS of 0, either ER positive or unknown, and had not received prior hormone therapy for metastatic disease. Overall objective response was observed in 9 (27%) patients. Complete response was observed in 2 cases and partial response in 7 patients. Median duration of response was 7 months (range 2–10). A higher response rate was observed in patients with predominantly soft tissue disease (38%) compared to patients with either dominant bone (18%) or visceral lesions (17%). Toxicity was mild and reversible: low grade fever in 30% of patients and flu-like symptoms in 9% of cases. It appears that IFN-B does not improve the efficacy of tamoxifen in an unselected population of metastatic breast cancer.
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  • 34
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 39 (1996), S. 315-319 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; month of birth ; Japan
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Recent studies suggest that prenatal or early post-natal factors may influence future breast cancer risk. To investigate whether month of birth is a risk factor for breast cancer, we analyzed the distribution of month of birth for 81,162 women died of breast cancer and 1,334,650 women died of cancers at all sites, who were reported to the Ministry of Health and Welfare from 1972–90 in Japan. After considering each birth year seasonal variations in month of birth were not shown statistically significant in any age-group through usingχ 2 test (df = 11). The negative results were also confirmed in residential area and period category.
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  • 35
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; protein tyrosine kinase ; prognostic factors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Protein tyrosine kinases (PTKs) are a family of enzymes sharing a highly conserved catalytic domain which phosphorylates substrate proteins on tyrosine residues. PTKs play a major role in the transduction of the mitogenic signal and are involved in the control of cell proliferation, differentiation, and transformation processes. PTKs can be subdivided into two major types: membrane associated PTKs consisting essentially of growth factor receptors (receptor tyrosine kinases or RTKs) and cytosolic PTKs involved in the intracellular transduction of mitogenic and differentiation signals. From January 1988 to January 1992, PTK activity was assayed in cytosolic fractions prepared from 350 T1-T2, N0-N1 M0, breast carcinomas. Enzymatic activity was measured using phosphate transfer from [32P]-ATP to poly-Glu-Tyr as an artificial substrate. According to our previously reported pilot study, we chose a cut-off value of 12 pmol32P incorporated min−1 mg−1 protein, corresponding to the median value. We found positive PTK levels (≥ 12 pmol/min/mg) to be correlated with a loss of differentiation according to Scarff-Bloom grade (p 〈 0.001), negative PR (p = 0.03) and ER status (p = 0.04). With a median follow-up of 30 months (0–82), patients with a positive PTK level presented a smaller 3-year disease free survival than in the PTK negative group of patients (p = 0.07). In Cox multivariate analysis including pT, pN, Scarff-Bloom grade, PR and ER, PTK activity does not emerge as a significant prognostic factor.
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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 38 (1996), S. 209-216 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; bone metastases ; osteoblasts ; osteolysis ; parathyroid ; prostaglandins
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The pathogenesis of breast cancer-induced osteolysis remains largely unknown. To evaluate the potential role of osteoblasts as target cells during this process, we incubated SaOS-2 human osteoblast-like cells (OBL) with culture media conditioned by proliferative (PM, ‘Proliferation Media’) or confluent (CfM, ‘Confluence Media’) MCF-7 human breast cancer cells. CfM decreased the growth of OBL by 26% (P 〈 0.01) while PM was without significant effect on this parameter. In contrast, both PM and CfM obtained from MCF-7 cultures increased the cyclic AMP (cAMP) response of OBL to the osteolytic agents PTH (10−8 M) and PTH-related peptide (PTHrP, 10−8 M) by a factor of about 3 (P 〈 0.001), and to prostaglandin E2 (PGE2, 10−6 M) by a factor of about 2 (P 〈 0.01). No significant modulation of OBL growth or sensitivity to PTH, PTHrP, or PGE2 was induced by media obtained from HBL-100 non-malignant immortalized breast epithelial cell cultures. 17β-estradiol (E2, 10−8 M) and the antiestrogen tamoxifen (Tam, 10−7 M) added for 48 h to MCF-7 cultures before collecting conditioned media attenuated and potentiated, respectively, the PM- but not the CfM-induced increase in the response of OBL to PTH or PTHrP. Along the same line, the addition to MCF-7 conditioned media of a polyclonal anti-transforming growth factor-β (TGF-β) antibody attenuated by about 25% (P 〈 0.01) the PM-induced increase in OBL response to PTH and PTHrP while abrogating the modulatory effects of E2 and Tam on that response. Together, our results indicate that MCF-7 breast cancer cells secrete factors which inhibit the growth of OBL and increase their sensitivity to various osteolytic agents. TGF-β was only partly responsible for these effects, and accounts for their modulation by E2 and Tam. The identification of other osteoblast-modulatory factor(s) should contribute to a better understanding and treatment of breast cancer-induced osteolysis.
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  • 37
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 38 (1996), S. 259-264 
    ISSN: 1573-7217
    Schlagwort(e): prostate specific antigen ; breast cyst fluid ; gross breast cystic disease ; breast cancer ; prognostic markers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary We demonstrate for the first time that prostate specific antigen (PSA) is a component of breast cyst fluid. At the cutoff level of 0.01 or 0.03 µg/L of PSA, 64% or 43% of cyst fluids are positive for PSA, respectively. PSA in cyst fluid, as characterized by high performance liquid chromatography, exists in almost equal concentrations as free PSA, with a molecular weight of 33 KDa, and as PSA bound to α1-antichymotrypsin, with a molecular weight of 100 KDa. PSA presence was also characterized in cyst fluid by Western blot analysis. These data suggest that PSA is a frequent component of breast cyst fluid. More studies are needed to establish the role of this serine protease in normal breast, gross breast cystic disease, and breast cancer.
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  • 38
    ISSN: 1573-7217
    Schlagwort(e): age at birth ; breast cancer ; epidemiology ; reproductive factors ; risk factors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Associations between parity and the risk of breast cancer, and the relative importance of age at first and age at last birth on breast cancer risk, were estimated in a case-control study nested in a nation-wide cohort of Swedish women born between 1925 and 1960. A total of 12,782 women with breast cancer and five times as many individually age-matched controls, aged less than 60 years with concomitant fertility information, were included in the analysis. Increasing parity was associated with a pronounced decrease in the risk of breast cancer with each additional birth conferring a 10 percent risk reduction (odds ratio 0.90 [95% CI 0.88–0.91]). In an analysis limited to women with two or more parities, and after adjustment for the effects of ages at interim births, the risk of breast cancer increased by about 13 percent for each five-year increment in age at first birth (odds ratio 1.13 [1.08–1.19]). For every five year-increase in age at last birth there was a small risk increase of marginal statistical significance (odds ratio 1.05 [1.01–1.09]). The present findings contradict recent claims that age at last birth has a stronger effect than age at first birth on breast cancer risk. The dominance of age at first birth as risk modulator is likely to reflect the protection afforded by the terminal differentiation of breast cells induced by a first pregnancy.
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  • 39
    ISSN: 1573-7217
    Schlagwort(e): aberrant estrogen receptor ; tamoxifen aziridine ; breast cancer ; hormone dependence
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Expression of estrogen receptor (ER) is a helpful predictor of response to endocrine therapy and disease free survival in breast cancer patients. The presence of variant estrogen receptors has been demonstrated at the RNA/DNA level and might represent an escape of tumors from hormonal control mechanisms. However, the demonstration that the corresponding peptides do exist is a real challenge. Denaturing polyacrylamide gel electrophoresis (SDS-PAGE) of covalently bound [3H]tamoxifen aziridine ([3H]TAZ) to ER demonstrates a specific, multiband peptide pattern recognized by anti-ER monoclonal antibodies (anti-ER Mo Abs). The native 66 kDa ER form identified through its hormone binding domain by the H-222 Mo Ab was the most prominent one followed by 50, 35, and 28 kDa forms on fluorography. Such patterns from early human breast tumors were compared to the ones of more advanced disease, namely large primary breast cancers, metastatic lymph nodes, and soft tissue relapses: in these cases, molecular forms of 43 and 35 kDa were identified with a remarkable consistency. The 43 kDa peptide was more frequently identified by the H-226 Mo Ab (which maps a region near the DNA binding domain) — albeit with low labeling intensity as compared to H-222 Mo Ab. In addition, the 43 kDa peptide was inversely correlated to ER levels. This altered ER or related peptide could potentially be a marker of biologically aggressive breast tumors.
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  • 40
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; polymerase chain reaction ; estrogen receptor ; progesterone receptor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The biochemical assay for estrogen (ER) and progesterone receptors (PR) as a routine procedure in the clinical evaluation of human breast cancer is well established. Since there are various and complex phenotypic alterations in breast cancer, there is a need for a multiparametric assessment of the biological profile of breast tumours. However, multiparametric analysis requires a large amount of tissue and various methods of quantitative analysis involving expensive reagents. Thus, an evaluation of the diagnostic and prognostic applications of the measurement of mRNA expression by reverse transcription polymerase chain reaction (RT-PCR) has been initiated. A series of 105 surgical samples of breast cancer was assayed for ER and PR expression in parallel by semi-quantitative RT-PCR and standardized enzymoimmunoassays (EIA). 79 (75%) tumour samples were positive for ER expression by EIA, and 86 (82%) by RT-PCR. This shows a good concordance of the two methods (90%). In the case of PR expression 65 (62%) tumour samples were positive by EIA and only 53 (51%) samples by RT-PCR. In conclusion ER-RT-PCR appears to provide information concerning ER expression similar to ER-EIA, and may be an alternative to this assay. The information derived by PR-RT-PCR appears somewhat different from PR-EIA. We are currently evaluating the biological and clinical significance of this discrepancy.
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  • 41
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 41 (1996), S. 123-130 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; prognosis ; Quetelet's index ; hormone receptors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The present study consists of 1,238 women with unilateral breast cancer treated with modified radical mastectomy living in the geographic area of Haukeland Hospital. Their weight and height had been measured years before presentation of the disease. Age-adjusted Quetelet's index (weight/height2) showed that obese women had a 49% higher risk of dying from breast cancer than lean ones. The relative risk decreased slightly when adjusted for tumour diameter, lymph node status, and mean nuclear area of the tumour cells. The prognostic effect of Quetelet's index was examined according to the estrogen and/or progesterone receptor status of the tumour. In patients with a hormone receptor positive tumour, obese women had a risk that was more than three times higher than lean ones. In patients with hormone receptor negative tumour, the effect of obesity was reversed, lean patients having a risk that was more than six times higher than obese ones, even after adjustment for lymph node status, tumour diameter, and mean nuclear area. Quetelet's index, while being a prognostic variable in its own right, thus acts differently in patients with hormone receptor positive and negative tumours.
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  • 42
    ISSN: 1573-7217
    Schlagwort(e): ELISA ; breast cancer ; plasminogen activator inhibitor-2 ; prognosis ; urokinase receptor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The levels of uPA, its inhibitors PAI-1 and PAI-2, and the uPA receptor (uPAR) have prognostic value in breast cancer. However, different extraction methods and assays kits are used in different laboratories and may directly influence the levels observed. To define a buffer suitable for both PAI-2 and uPAR extraction from breast cancer tissue compatible with hormone receptors and other cytosolic prognosticator assays, we compared PAI-2 and uPAR values obtained by immunoenzymatic assays (American Diagnostica, Green-which, USA) in several extraction conditions: 1) cytosol obtained with the standard hormone receptor buffer; 2) solubilized pellets obtained by Triton X100 extraction of the pelleted membranes obtained with standard hormone receptor buffer; 3) cytosol obtained by direct extraction in the buffer (containing Triton X100) recommended by the manufacturer, after 2 hours or 12 hours of incubation. Cytosol extracts prepared using the standard procedure recommended for hormone receptors gave the highest PAI-2 values. The highest uPAR values were obtained in the subsequent detergent extraction of the pelleted membranes. PAI-2 levels obtained with the kit manufacturer's method after 12 hours of incubation were lower than those obtained after 2 hours of incubation, whereas uPAR levels were similar. We conclude that the most suitable extraction protocol employs standard hormone receptor extraction buffer to obtain a supernatant cytosol fraction for PAI-2 assay, and subsequent detergent extraction of the pelleted membranes to obtain an extract suitable for uPAR.
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  • 43
    ISSN: 1573-7217
    Schlagwort(e): ATP bioluminescence ; breast cancer ; chemosensitivity assay ; doxorubicin ; mitoxantrone ; multidrug resistance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Apart from clinical trials, mitoxantrone (MX) is rarely used in breast cancer (BC) due to the anticipated anthracycline cross-resistance. We have examined this drug versus doxorubicin (DOX) using data obtained fromin vitro microplate ATP tumor chemosensitivity assays (ATP-TCA) of BC cells which were derived from 55 chemotherapy-naive patients at time of primary surgery. Both drugs were tested at 6 different concentrations ranging from 6.25% to 200% peak plasma concentrationin vivo (PPC). Differences between DOX and MX observed for mean IC50, IC90, and a sensitivity index (SI) were not statistically significant.In vitro response rates were 44% for DOX and 52% for MX. 34 of 52 eligible assays (65%) showed comparable activity of both drugs whereas a lack of cross-resistance was observed in the remaining 18 (35%) tumors as indicated by differences for SI. Cumulative concentration-response plots of tumors respondingin vitro with a ≥ 50 percent or ≥ 90 percent tumor cell inhibition showed a strong dose-dependence for both DOX and MX at concentrations which normally can be achieved within clinical tumors (i.e. 6.25%-50% PPC). At higher concentrations, however, cytotoxicity of DOX and MX could not be improved by furtherin vitro dose escalation. Moreover, a substantial proportion of BC specimens (DOX: 48.1%; MX: 40.4%) did not experience a ≥ 90 tumor cell inhibition at 200% PPC. In conclusion,in vitro results obtained by ATP-TCA indicate that there is no cross-resistance between MX and DOX in a substantial proportion of BC patients. This may be clinically useful and suggests that combinations including MX should be tested in patients clinically resistant to DOX containing regimens. Since both drugs produced sigmoidal concentration-response curves, dose escalation beyond a certain point may not produce increased sensitivity.
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  • 44
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; tumor dormancy ; recurrence risk ; metastasis growth
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose To gather information on metastatic growth from the time-distribution of first treatment failure in breast cancer patients undergoing mastectomy alone.Methods: The risk of recurrence at a given time after surgery was studied utilizing the cause-specific hazard function. Recurrence was categorized as first treatment failure at any site, local-regional recurrence, distant metastases, and contralateral tumor. The risk distribution was assessed relative to tumor size, axillary lymph node involvement, and menopausal status.Results: A total of 1173 patients treated between 1964 and 1980 with mastectomy alone and no adjuvant therapy were studied. The hazard function for first failure presented an early peak at about 18 months after surgery, a second peak at about 60 months and then a tapered plateau-like tail extending up to 15 years. A similar risk pattern was detectable for both local recurrence and distant metastases, while the curve of contralateral breast tumors showed a near flat plateau. The risk of early local-regional and distant recurrences was much lower for tumors less than 2 cm in diameter than for larger tumors; the risk of late recurrence was similar for small and large primaries. Node-positive patients showed peaks four to five times higher than node-negative patients. Subdividing node-positive patients into 1–3 and 〉 3 node-positive subsets did not substantially change the general picture of tumor recurrence. The hazard functions for premenopausal and postmenopausal patients were virtually superimposable.Conclusions: The multipeak hazard curve suggests that the process resulting in overt clinical metastases may have discrete features. Primary tumor size could affect in different ways early and late metastases, while axillary node status should be related to the risk level, not to the risk pattern, and menopausal status does not seem to significantly affect the hazard distribution. Moreover, contralateral breast tumors, occurring at constant risk throughout the time, should be considered as second primary cancers. These findings could be reasonably explained by a tumor dormancy hypothesis, which assumes that micrometastases may be in different biological steady states, most of which do not imply tumor growth. Tumor or microenvironment changes could induce metastatic growth after given mean transition times from surgery and originate a discrete pattern of the hazard function.
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  • 45
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; Ki-67 ; nodal status ; prognostic variables
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary An immunohistochemical determination of the growth fraction (GF) with the Ki-67 monoclonal antibody has been performed in a prospective series of 140 patients with primary operable breast carcinoma. GF ranged from 0% to 43% Ki-67 stained cells with a median value of 8%. High GF (〉 8%) was significantly associated with axillary node involvement (p = 0.006), aneuploidy (p = 0.008), histologic grade (p = 0.03), and S-phase fraction 〉 5% determined by flow cytometry (p = 0.01). After a median follow-up of 6 years, the univariate analysis did not show significant correlation between high GF and worse relapse-free survival (p = 0.10) or shorter overall survival. However, a multivariate analysis on relapse-free survival, performed in 127 comparable patients, showed that GF was an independent predictive factor (p = 0.03) together with nodal status (p = 0.00001), age under 45 years (p = 0.0008), and chemotherapy (0.006). In node negative patients, GF was still an independent prognostic indicator (p = 0.002) together with age under 45 years (p = 0.0003). Tumor proliferative activity evaluated by the monoclonal antibody Ki-67 appears to be an effective indicator of prognosis in breast cancer and could be of assistance in the decision making of adjuvant therapy in node negative patients.
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  • 46
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 38 (1996), S. 253-258 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; cycle length ; menstrual cycles ; regularity ; risk
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The effect of regularity and length of the menstrual cycle on breast cancer risk was studied prospectively in 78 cases and 383 age-matched controls who participated in a breast cancer screening programme, the DOM-project, in Utrecht, the Netherlands. Before entering the screening programme when they were aged 41–46, the women kept a menstrual calendar during at least three consecutive cycles. Cycles were considered to be irregular if any of three cycles was shorter than 21 days or longer than 35 days and/or if variation between cycle lengths was more than five days. Women with irregular cycles had a significantly reduced risk of breast cancer (odds ratio = 0.44; 95% confidence interval 0.22–0.86) after adjustment for age at menarche, age at first birth, parity, Quetelet's index and family history of breast cancer. Among regularly menstruating women, long cycles (28 days or more) were not significantly associated with increased risk of breast cancer (odds ratio 1.17; 95% confidence interval 0.66–2.09). To the extent that irregular menstrual cycles reflect anovulatory cycles, our findings support the hypothesis that the cumulative number of regular ovulatory cycles increases breast cancer risk.
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  • 47
    ISSN: 1573-7217
    Schlagwort(e): adjuvant therapy ; breast cancer ; ovarian irradiation ; prednisone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Following mastectomy, patients aged 35 to 76 years with operable breast cancer underwent postoperative irradiation of the chest wall and regional lymph nodes. They were then assigned at random to receive no further therapy (NT), ovarian irradiation (R) 2000 rads in 5 days, or ovarian irradiation in the same dosage plus prednisone (R + P) 7.5 mg daily for up to five years. A total of 703 eligible patients received the randomly assigned treatment. The median follow up was 21 years with a range of 14 to 25 years. Overall, there was a delay in recurrence (p = 0.03) and survival was prolonged (p = 0.19) for patients who received R, but in neither case was the difference significant after adjusting for the multiplicity in our data. Overall, patients who received R + P experienced a significant delay in recurrence (p = 0.0003) and a significantly prolonged survival (p = 0.005), even after adjusting for multiple comparisons. In premenopausal patients who received R, the recurrence of breast cancer was delayed and survival prolonged, but not significantly. In premenopausal women aged 45 years or more, R + P therapy significantly prolonged survival (p = 0.0004), while the delay in recurrence although significant (p = 0.02) was only marginally so after allowance for multiple comparisons. No value was demonstrated for ovarian irradiation with or without prednisone therapy in postmenopausal patients. A new finding in this review was that contralateral breast cancer as the first failure was reduced by R + P compared to NT in the overall group.
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  • 48
    ISSN: 1573-7217
    Schlagwort(e): INT2 ; ERBB2 ; amplification ; expression ; breast cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The relationships of INT2 and ERBB2 amplification and of ERBB2 overexpression in primary breast tumors to prognostic factors, recurrence, and survival have generated considerable controversy. The rationale for this study is that long-term, recurrence-free survival is a more direct criterion for testing the validity of a tumor marker than correlation either with prognostic factors or with short-term recurrence and survival. We examined the association of recurrence with INT2 and ERBB2 amplification and ERBB2 expression by comparing primary breast tumors from patients surviving without recurrence for ≥ 8.5 years after diagnosis. the LTS group, to tumors from patients recurring within two years, the RR group. The RR (N = 63) and LTS (N = 61) samples were coded and examined for amplification by Southern blotting and for expression by immunohistochemistry. Comparison between the RR and LTS groups demonstrated that INT2 amplification was associated with a significantly (P = 0.018) higher (5.6-fold) risk of recurrence, an association that remained significant after controlling for lymph node (LN), tumor size (TS), and histograde (HG) status. ERBB2 amplification and expression were not associated with a higher recurrence risk. Survival analyses within the RR group, however, demonstrated significantly shorter survival time among cases with than without ERBB2 amplification (P = 0.018, median survival 16 vs 25 months), or ERBB2 expression (P = 0.019, median survival 15 vs 25 months), but not INT2 amplification. Univariate Cox proportional hazards regression models also demonstrated significantly shorter survival among cases with ERBB2 amplification (P = 0.016) or expression (P = 0.049), that remained significant in multivariate analyses (P = 0.022) for ERBB2 amplification. These results indicate a significant positive association between INT2 amplification and risk for tumor recurrence in the RR as compared to the LTS group. The relationship of ERBB2 amplification or overexpression to patient outcome is more complex. ERBB2 amplification and expression have a significant relationship with shorter survival among patients recurrent within two years, but their occurrence in tumors from women surviving without recurrence for ≥ 8.5 years suggests that ERBB2 status is not predictive of shorter survival for all breast cancers.
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  • 49
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 40 (1996), S. 1-9 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; ethnicity ; minorities ; prevention ; race ; screening
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In 1986, the National Cancer Institute published its cancer control objectives for the nation, which included projected reductions in breast cancer mortality. The reductions were estimated to be 25.0% from reducing fat, 16.0% from expanding use of breast cancer screening services, and 14.3% from expanding access to state-of-the-art breast cancer treatment. During the same decade, the U.S. population aged and became significantly more ethnically diverse, and accompanying this increase in ethnic diversity was endemic poverty, disproportionately experienced by black and Hispanic minorities. These populations may be seen as medically underserved. With respect to breast cancer, as well as many other cancers, the medically underserved are understudied, not well understood by many in the medical and academic research community, and attended by health care institutions that are under-funded and often do not have the resources necessary to ensure access to state-of-the-art cancer screening, clinical follow-up, diagnosis, and treatment. At the same time, medically underserved women are more likely to be diagnosed with late-stage breast cancer, and some groups (e.g. black women) bear the greatest breast cancer mortality burden in the nation. In this special issue of Breast Cancer Research and Treatment, eight papers describe what we know and what we don't about breast cancer prevention and control in medically underserved populations.
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  • 50
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 40 (1996), S. 65-74 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; treatment ; age ; race ; socioeconomic factors ; hospitals ; physician practice patterns
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Guidelines for the optimal treatment of breast cancer have been publicized over the past 15 years, yet clinical practices continue to vary substantially in the United States. This article reviews the literature on variations in local and systemic treatment of breast cancer by patient and provider characteristics. Studies of local therapy have consistently demonstrated that older women are less likely than younger women to receive radiation therapy after breast-conserving surgery. Some studies have noted that black women are less likely than white women to receive breast-conserving surgery and less likely to receive radiation therapy after breast-conserving surgery. Rates of breast-conserving surgery vary three-fold among geographic regions and between teaching and non-teaching hospitals. Patients at smaller hospitals appear less likely to receive indicated radiation therapy. Patterns of systemic therapy have not been well described. Women over age 75 may not be receiving adequate hormonal therapy, but recent data are not available. Limited data suggest that rates of systemic therapy do not vary substantially by race or Hispanic ethnicity, but women without health insurance may not be receiving appropriate chemotherapy. Studies relating hospital and physician characteristics to the use of systemic therapy are sparse and inconclusive. In order to increase the proportion of women who receive optimal treatment for breast cancer and ensure greater equity, a more sophisticated understanding of variations in clinical practice will be required. These variations may arise from insufficient knowledge of or disagreement with guidelines among physicians, inadequate communication between physicians and patients, and individual preferences or clinical attributes of patients. Future studies will need to explore the dialogue between women and their physicians that leads to decisions about treatment of breast cancer.
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  • 51
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 40 (1996), S. 141-149 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; prolaction ; signal transduction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The polypeptide hormone prolactin (Prl), acting through its cell surface receptors, promotes growth and differentiation in normal and malignant breast cells. We demonstrate herein that two Prl-responsive cell lines, NOG-8 normal mouse mammary epithelial and T47D human breast cancer cells, respond to Prl by rapid and transient activation of a series of kinases.Raf-1 was activated within 2–5 min of Prl treatment. This was followed rapidly by activation of MEK (MAP kinase kinase) and MAP kinase activity in these cells. Increased MAP kinase activity was accompanied by tyrosine phosphorylation of both the 42 kDa and 44 kDa isoforms. The tyrosine kinase inhibitors genestein and tyrphostin blocked the increase in MAP kinase activity as well as Prl induced growth of the T47D cells. These results indicate that the Prl receptor, after binding to Prl in mammary cells, activates theraf-MEK-MAP kinase pathway for signal transduction leading to mitogenesis.
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  • 52
    ISSN: 1573-7217
    Schlagwort(e): prostate specific antigen ; breast cancer ; fibroadenomas ; steroid hormones ; steroid hormone receptors ; benign breast disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Prostate specific antigen (PSA) is a tumor marker used widely for the diagnosis and monitoring of prostatic adenocarcinoma. Recently, we provided evidence that PSA may also be produced by breast tumors. In this report we examined quantitatively the PSA levels in 199 breast tumors, 48 tissues with benign breast disease (BBD, 34 fibroadenomas), and 36 normal breast tissues. Significant amounts of PSA (≥ 0.030 ng of PSA per mg of total protein) were found in 28% of breast tumors, 65% of BBD tissues, and 33% of normal breast tissues. PSA positivity in breast tumors was highest in stage I disease (34%) and decreased with disease stage (24% in stage II and 18% in stage III–IV). Using polymerase chain reaction amplification we have shown PSA mRNA presence in patients with PSA protein-positive tissues (benign and malignant) but not in patients with PSA protein-negative tissues. Our data suggest that PSA is expressed frequently by normal breast tissue, by tissue of benign breast diseases, and by breast cancer tissue. Highest expression is seen in benign breast disease and lowest expression in advanced stage cancerous tissue. As PSA production is mediated by steroid hormones and their receptors, we propose that PSA may be a new marker of steroid hormone action in the normal or diseased female breast. The role of this enzyme in the development of breast diseases including breast cancer is currently unknown.
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  • 53
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; cell lines ; estrogen receptor ; nitric oxide ; nitric oxide synthase ; RT-PCR
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary For various human tumor cell lines (neuroblastoma, cervix carcinoma) the presence of constitutive nitric oxide synthase (cNOS) has been documented. Here, for the first time, we report about cNOS expression in 10 of 16 human breast cancer cell lines. cNOS expression correlates strongly with expression of estrogen receptor (ER). Competitive reverse transcription — polymerase chain reaction (cRT-PCR) was used to detect cNOS and ER mRNA expression. Our findings suggest that estradiol could stimulate constitutive NO release in breast tissue, where it acts as a free radical.
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  • 54
    ISSN: 1573-7217
    Schlagwort(e): apolipoproteins ; breast cancer ; cardiovascular disease ; lipoproteins ; lipoprotein(a) ; tamoxifen
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Serum lipids and apolipoprotein levels were measured in twenty postmenopausal women with primary breast cancer, before and three months after tamoxifen therapy (10 mg twice a day). Tamoxifen caused a significant reduction in total serum cholesterol (10%;P 〈 0.02), and in low-density lipoprotein cholesterol (17%;P 〈 0.01), and a significant 47 % increase in the subclass 2 of the high density lipoprotein cholesterol (P〈 0.01). In addition, tamoxifen caused a 16% increase in apolipoprotein A-I, a 12% decrease in apolipoprotein B (P 〈 0.05), and a 37% reduction in the serum concentration of lipoprotein(a) (P〈 0.01). These results show that tamoxifen brings about an important improvement in serum lipid profile.
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  • 55
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; cRT-PCR ; fibrinolytic system ; plasminogen activator ; uPA-R expression
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The conversion of plasminogen to active plasmin is thought to be a crucial step in the process of extracellular matrix degradation associated with metastatic spread. Activation of plasminogen is initiated by urokinase plasminogen activator (uPA). The binding of uPA to the uPA cell surface receptor (uPA-R) accelerates plasmin generation from plasminogen and localizes uPA activity to the cell surface. We investigated the mRNA-expression of uPA-R in 19 different human breast cancer cell lines. In a competitive reverse transcription polymerase chain reaction (cRT-PCR) we simultaneously co-amplified two different RNA templates bearing the same primer recognition sequences, the cell line RNA and a known amount of anin vitro synthesized uPA-R-RNA internal standard. We analyzed the two PCR products differing 50 bp in size by agarose gel electrophoresis and calculated the initial uPA-R-RNA template concentration from the relative intensities of the bands quantified by video densitometry. We grouped the investigated cell lines according to theirin vitro invasiveness according to literature. Cell lines with a high potential of invasiveness showed a higher expression of uPA-R compared to those with a low potential of invasiveness (Student's t-test,p 0.04). In addition to that we compared the uPA-R mRNA levels with uPA-R, uPA, and PAI-1 protein levels in culture supernatants and cell lysates. The obtained results in breast cancer cell lines with different invasiveness and in benign epithelial cell lines revealed the complex cooperation of the urokinase type proteolytic pathway. uPA, uPA-R, and PAI-1 are to be considered as a diagnostic tool rather than assaying a particular molecule alone. Our findings support the hypothesis that the urokinase proteolytic pathway plays a central role in the acquisition of an invasive phenotype and favors its potential use as a prognostic marker in patients with breast cancer.
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  • 56
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 40 (1996), S. 283-293 
    ISSN: 1573-7217
    Schlagwort(e): axillary lymph node metastases ; breast cancer ; diagnosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The diagnosis of axillary (AX) metastases remains a challenge in the management of breast cancer and is a subject of controversy. Clinical node staging clearly is limited in the assessment of AX lymph nodes. AX mammography, ultrasonography, and computed tomography (CT) do not provide histologic information. Although nuclear magnetic resonance imaging may have considerable value in the diagnosis of AX metastases, it does not detect micrometastases. The use of biologic markers in the assessment of AX metastases remains a subject of investigation. On the other hand, biopsy of selected AX nodes or tissue with examination of histology or cytology generally would not identify a significant percentage of patients with AX node involvement. Sentinel lymph node biopsy, however, might be potentially useful for assessing AX metastases, although it remains investigational. In order to simplify diagnosis and reduce morbidity and mortality, alternatives to AX dissection must be sought and imaging and staging modalities refined. We present a review of the literature pertaining to the diagnosis of AX metastases in patients with breast cancer and a discussion of some current areas of controversy.
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  • 57
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 39 (1996), S. 261-273 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; quality of life ; survivorship
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Attention to the quality of life (QOL) among long-term of breast cancer is long overdue. Modest improvements in overall survival have led to a greater emphasis on how women are living with the disease. The purpose of this paper is to report the results of a descriptive study that evaluated the quality of life of 294 breast cancer survivors, and to review the continuum of positive and negative QOL outcomes in this population. Members of the National Coalition for Cancer Survivorship (NCCS) were surveyed and received two QOL instruments: the Quality of Life — Cancer Survivors Tool (QOL-CS) and the Functional Assessment of Cancer Therapy (FACT-G), and a demographic data tool. The main research variables were the subscales (Physical, Psychological, Social, and Spiritual Well-being) and individual items of the QOL-CS and the FACT-G. Results indicated that: a) fatigue, aches and pains, and sleep problems were persistent after treatment ended; b) psychological distress from cancer diagnosis and treatment, and fear of recurrent, metastatic, and recurrent disease were problematic over time; c) family distress, sexuality, and family burden issues were of greatest social concern; and d) uncertainty over the future plagued breast cancer survivors long-term. Breast cancer survivors also reported good outcomes in hopefulness, having a life purpose, and having a positive change after the treatment. Conclusions: breast cancer survivors experienced long-term changes after completion of treatment which affected overall quality of life. However, many positive benefits were also gained which helped to balance the worse outcomes.
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  • 58
    ISSN: 1573-7217
    Schlagwort(e): adjuvant tamoxifen ; breast cancer ; femoral fractures ; postmenopause
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The anti-estrogen tamoxifen is the prevalent endocrine treatment in postmenopausal breast cancer patients. However, nothing is known about the long-term effects of the drug on the skeleton as assessed by the occurrence of fractures. We investigated the occurrence of fractures of the femur in patients from a Danish Breast Cancer Cooperative Group (DBCG) trial initiated in 1977 by a linkage of data from the Danish National Registry of Patients with data from the DBCG registry. 1716 postmenopausal women with high-risk breast cancer were randomized to local radiotherapy with or without tamoxifen, 30 mg daily for 1 year. Fifty-one patients in the control group had one femoral fracture and 64 tamoxifen treated patients had one femoral fracture. Eleven patients in the control group had one trochanteric fracture compared to 27 patients in the tamoxifen group (logrank = 5.28, P = 0.022; hazard ratio = 2.12, 95% CL 1.12, 4.01). The results could not be explained by a longer survival in the tamoxifen group nor by bone metastases with pathological fractures. In conclusion, our study suggests that tamoxifen does not seem to offer protection against fractures in old age and may even increase the risk of fractures at particular sites. This hypothesis needs to be disproved or confirmed in other trials.
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  • 59
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; disease-free interval ; estrogens
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The influence of plasma estrogen levels on disease-free interval (time from primary treatment to first relapse, DFI) in breast cancer patients is not known. Any relation between plasma estrogens and the outcome in breast cancer patients may have implications considering use of hormone replacement therapy (HRT) in patients treated for breast cancer. We measured plasma estradiol (E2), estrone (E1), and estrone sulfate (E1S) in 92 postmenopausal women with breast cancer relapse and correlated plasma estrogen levels to the length of their disease-free interval (DFI1) and the length of the DFI in the subgroup of patients in whom this extended a time period of more than 2 years (DFI2). The length of DFI2 correlated negatively to plasma level of E1S (p 〈 0.025) and E2 (p 〈 0.05) and to the E2/E1 and E1S/E1 ratios (p 〈 0.05), while the length of DFI1 correlated negatively to plasma level of E1S (p 〈 0.025) and the E1S/E1 ratio (p 〈 0.005). We also analyzed for possible correlations between DFIs and plasma estrogen levels in subgroups based on tumor stage at diagnosis and previous therapy. In general, these subgroup analyses revealed negative correlations of statistical significance or borderline significance between the DFI1 and DFI2 and E2 and the E2/E1 ratio and non-significant negative correlations between plasma levels of E1S and DFI1 and DFI2. In particular, strong negative correlations between plasma estrogen levels and the length of DFI1 and DFI2 were found among patients responding to first line endocrine treatment for relapse and among patients with primar stage III tumors. Our findings suggest plasma E2 and E1S to stimulate the growth of micrometastases in patients treated for breast cancer.
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  • 60
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 37 (1996), S. 29-37 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; esculetin ; indomethacin ; linoleic acid ; NDGA ; piroxicam
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We investigated the effects of cyclooxygenase and lipoxygenase inhibitors in the presence of linoleic acid (LA), as well as the direct effects of prostaglandin E (PGE) and leukotriene B (LTB) on a human breast cancer cell line (MDA-MB-231)in vitro. Piroxicam, esculetin, and nordihydroguaiaretic acid (NDGA) suppressed cell growth and thymidine incorporation. However, a low concentration (1 µg/ml) of indomethacin (INDO) stimulated cell growth and thymidine incorporation, while a high concentration of INDO (30 µg/ml) inhibited both. Esculetin and NDGA reduced the secretion of LTB, whereas piroxicam reduced the secretion of PGE. INDO reduced the secretion of PGE, but a low concentration of INDO increased the secretion of LTB. Consequently, cell growth was correlated with the PGE and/or LTB concentrations when the cells were treated with these cyclooxygenase or lipoxygenase inhibitors. On the other hand, exogenous PGE2 partially reversed the inhibition of thymidine incorporation caused by INDO, whereas LTB4 exerted a similar effect in the case of esculetin or NDGA. The reversibility of the piroxicam effect with PGE2 is not convincing. Therefore, it is suggested that the growth of MDA-MB-231 cellsin vitro is affected by both the lipoxygenase and cyclooxygenase products, probably the other eicosanoids rather than PGE2 and LTB4.
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  • 61
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; liver neoplasms ; liver ; ultrasound
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Retrospective analysis of the medical records of 6649 breast cancer patients seen over an 11-year period found 438 patients (6.6%) with liver metastases (LM) and 432 patients (6.5%) with benign liver lesions (BLL). Liver ultrasonography (LUS) and liver function tests had been performed for all patients. LM were the first manifestation of metastatic spread in 20.1% of the 438 patients; median survival was related to the presence (6.7 mo.) or absence (12.2 mo.) of extrahepatic metastases (EHM). Liver function tests were normal in 20.5% of the patients in whom LM were first diagnosed by LUS. Most LM were hypoechoic (70.9%). BLL corresponded to cysts, hemangiomas, calcifications, and focal fatty infiltration. LUS appears indicated for (i) pretherapy disease staging, and in particular for detection of BLL, and (ii) follow-up of patients without EHM for early diagnosis of LM.
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  • 62
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; immunocytochemistry ; Ki-S1 antibody ; prognosis ; proliferation markers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In a series of 205 node-negative breast cancers (NNBC), we determined staining by the novel antibody Ki-S1, a marker of tumor cell proliferation, in order to test its association with other prognostic variables and its prognostic significance. Ki-S1 was determined in routinely formalin-fixed paraffin-embedded tumor samples. Ki-S1 gave a nuclear staining in the majority of the carcinomas (188 of 205), with percentages of reacting nuclei ranging from 2% to 90% (median value of 7%). In 107 tumors frozen sections were available to also assess the Ki-67 antibody. Among these, 94 had a nuclear staining of cancer cells ranging from 5% to 80% (median value of 7%). In 46 tumors we also determined the MIB-1 antibody. The percentage of MIB-1 nuclear staining ranged from 1% to 50% (median value of 20%). There was no significant relationship between Ki-S1 and the other two cell kinetic markers. Ki-S1 labeling was significantly associated only with tumor size (p = 0.03). With a median follow-up of 6 years, Ki-S1 had no significant prognostic value for either relapse-free survival (RFS) or overall survival (OS)(Ki-S1 as continuous logarithmic variable; p = 0.86 and p = 0.23, respectively). For RFS the following variables had a significant prognostic value: Ki-67 (≤ 10% vs 〉 10%; p = 0.037); progesterone receptor (PgR) expression (− vs +/++; p = 0.041); tumor size (pT1 vs pT2−3; p = 0.042) and grading (GI vs GII−III; p = 0.047). For OS, tumor size (p = 0.0044), age (continuous variable; p = 0.0060), and Ki-67 (p = 0.043) were significantly prognostic. In multivariate analysis (final model), only tumor size retained a significant and independent prognostic value for RFS (p = 0.0042). For OS, both tumor size (p = 0.0029) and age (≤ 55 years vs 〉 55 years; p = 0.041) retained significance in the multivariate model. In conclusion, Ki-S1 does not seem to have prognostic relevance in this series of NNBC. Possible hypotheses to explain this observation are discussed.
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  • 63
    ISSN: 1573-7217
    Schlagwort(e): absorptiometry ; bone minerals ; breast cancer ; neutron activation analysis ; tamoxifen
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Oestrogen levels play a major role in conditioning the rates of bone changes in women. Tamoxifen is a synthetic oestrogen antagonist commonly used as an adjuvant therapy for breast cancer. The goal of the present study was to study the amount and the elemental composition of bone minerals in the appedicular skeleton of women with breast cancer treated with adjuvant tamoxifen, as well as to investigate the possibility of increased risk for osteoporosis. Forty-two patients, aged 41–65 years, without skeletal metastases were studied. The mean duration of tamoxifen administration on a daily dose of 20 mg was 21 months (range 1–59 months). It was found that neither the amount of phosphorus in hands (HBP) nor forearm bone mineral content (BMC) differ statistically from those of age-matched healthy subjects. This was confirmed by reassessing bone mineral status after 30 months in 17 postmenopausal patients treated with tamoxifen for a mean time of 52 months. In conclusion, our data support that long-term tamoxifen treatment has no adverse or protective effect on the amount and elemental composition of the appedicular skeleton.
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  • 64
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; CA 15.3 ; CEA ; serum markers ; TPA ; tumor markers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The specificity and sensitivity of a tumor marker (TM) are important in establishing its potential clinical utility for a specific type of neoplasm. CA 15.3 is a TM specific for breast cancer; it is defined by two monoclonal antibodies (DF3 and 115D8), whose specificity, in disease-free follow-up patients, and sensitivity, in patients at diagnosis of first metastasis, have been evaluated in the present study and compared with those of carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA). Serum concentrations of all three TMs were quantified in 618 individuals: 80 healthy controls, 421 patients with local breast cancer who became free of disease following locoregional treatment, and 117 patients with disseminated disease at diagnosis of metastasis. Radioimmunoassay (RIA) was the method employed, and the cut-off values obtained were 30 U/ml for CA 15.3, 5 ng/ml for CEA, and 120 U/I for TPA. The results showed CA 15.3 and CEA specificities to be analogous (95.7 and 95.5%, respectively). TPA specificity (81.9%) was lower (p〈0.001). During adjuvant therapy, CA 15.3 serum levels were seen to increase, followed by a normalization of concentration after terminating therapy. On the other hand, CA 15.3 and TPA sensitivities (64.1 and 67.5%, respectively) were greater than for CEA (44.4%, p〈0.01). It is concluded that CA 15.3 is a useful TM for breast cancer, as it offers a greater sensitivity than CEA and a higher specificity than TPA. Combining CA 15.3 and CEA fails to increase CA 15.3 sensitivity, while combining CA 15.3 with TPA increases false-positives and so likewise offers no additional benefit.
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  • 65
    ISSN: 1573-7217
    Schlagwort(e): AgNORs ; breast cancer ; cell proliferation ; estrogen receptor ; PCNA ; progesterone receptor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The breast is a target organ for estrogens and progesterone. These hormones control several functions of the normal and abnormal mammary epithelium including cell proliferation. Most of the actions of estrogens and progesterone are mediated via specific steroid receptors, and one would expect that proliferating cells should contain estrogen receptors (ER) and/or progesterone receptors (PR). However, the correlation between receptor expression and cell proliferation is still controversial. In the present study we have examined 29 human breast cancer samples; in 17 of them we evaluated the simultaneous ER and PR localization with that of proliferating cell nuclear antigen (PCNA) and silver-stained nucleolar organizer regions (AgNORs) in a cell-by-cell study. We found that in almost 50% of the tumor biopsies examined, the cells expressing ER were significantly associated with elevated cell proliferation. In another group (38%) there were not significant differences between ER expression and cell proliferation. In only one of the samples (6%) the cells expressing ER showed lower cell proliferation. The study also revealed that in 44% of the tumors the PR expressing cells were associated with elevated cell proliferation. In a second group the PR expression was not significantly associated with cell proliferation (33% of the cases). Finally, in 22% of the samples the cells carrying PR showed lower cell proliferation. We also detected lower ER immunoreactivity in 30% of the breast cancer biopsies with one of the monoclonal antibodies against ER (antibody 1D5 directed against the A/B domain). This group of tumors was PR-negative (or very weakly positive) and had high proliferation. The presence of tumors with ‘abnormal’ ER proteins and displaying ER/PR significantly associated with elevated cell proliferation could have implications in human breast cancer treatment.
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  • 66
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 38 (1996), S. 201-208 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; cytogenetics ; FISH ; fluorescentin situ hybridization ; histopathology
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Conventional cytogenetics of breast and other solid tumors has been hampered by a number of factors. An analysis of breast tumor tissues was therefore undertaken using fluorescentin situ hybridization (FISH). A total of 34 specimens were analyzed using a chromosome 8-specific α-satellite probe. Various approaches were tested and compared. Among 30 informative samples, 11 infiltrating ductal carcinomas, not otherwise specified (NOS), 5 ductal carcinomasin situ, 5 lobular carcinomas, 3 papillary carcinomas, and 6 benign lesions were studied. Of the 11 cases of infiltrating ductal carcinomas (NOS) analyzed, four cases showed 3 signals, one case showed 4 signals, and the rest showed 2 signals. Of the 5 cases of ductal carcinomain situ samples, 1 showed 3 signals and the other 4 cases showed 2 signals. All cases of lobular carcinomas, papillary carcinomas, and benign lesions showed 2 signals. We inferred from these data that 36% of the infiltrating ductal carcinomas (NOS) were trisomic and 9% were tetrasomic, whereas 20% of the ductal carcinomasin situ were trisomic. All samples from lobular carcinomas, papillary carcinomas, and the benign lesions were disomic. From our preliminary data, it can further be concluded that a subset of breast cancer is characterized by chromosome 8 trisomy. These data are consistent with an ever-increasing database on the association of chromosomal 8 trisomy with other cancers such as leukemia, lymphoma, prostate cancer, ovarian carcinoma, salivary gland tumor, malignant melanoma, desmoid tumors, and recently gestational trophoblastic disease. It is also noted that the ability to analyze formalin-fixed, paraffin-embedded archival material will enable a more comprehensive cytogenetic study of breast cancer than is currently available.
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  • 67
    ISSN: 1573-7217
    Schlagwort(e): cathepsin D ; breast cancer ; RNA hybridisation ; stromelysin 3 ; urokinase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary We have compared by RNAin situ hybridisation on serial cryo-sections the distribution of cathepsin D (cath-D), stromelysin 3 (strom-3), and urokinase plasminogen activator (UPA) gene expression in different tissues of human benign and malignant mammary tumors. Cath-D expression was found to be higher in adenocarcinomas compared to non-tumoral glands. The cath-D RNA was located in mammary epithelial cancer cells rather than in fibroblasts, indicating that the cath-D gene was overexpressed in cancer cells, where the corresponding protein determined by immunohistochemical staining had been shown to be accumulated (P. Rogeret al., Human Pathol 25: 863–871, 1994). In contrast strom-3 RNA in adjacent tissue sections used as a control of tissue localisation was mostly expressed in peritumoral fibroblasts rather than in cancer cells confirming previous results of Bassetet al. and validating our methodology. UPA RNA was detected both in tumor cells and in stromal cells. In benign lesions the 3 protease RNAs were mostly found in epithelial cells. Stromal cells expressed UPA RNA in 5 of 7 lesions, cath-D and strom-3 in only one sample. We conclude that in breast cancer patients, cath-D gene expression is increased in epithelial mammary cancer cells at the RNA level as well as at the protein level, suggesting an altered transcriptional regulation. In non malignant lesions, the distribution was different with a predominant distribution in epithelial mammary cells for the 3 protease messenger RNA.
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  • 68
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 37 (1996), S. 89-92 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; ductal carcinomain situ ; ErbB-2 ; pS2 ; subtype
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary We examined the expression of ErbB-2 and pS2 proteins in 59 ductal carcinomain situ (DCIS) of the breast, either pure DCIS or DCIS associated with invasive carcinoma, using immunohistochemical staining of paraffin-embedded sections. Positive staining for ErbB-2 and pS2 proteins was noted in 32% (19/59) and 46% (27/59) of DCIS, respectively. An inverse relationship between ErbB-2 and pS2 status in DCIS was observed (p 〈 0.01). From the viewpoint of histological subtype, the prevalence of ErbB-2 protein expression was significantly higher in the comedo subtype than the cribriform-micropapillary subtype. The prevalence of immunoreactivity for ErbB-2 in solid subtype was intermediate between those of the other two groups. In contrast, the prevalence of pS2 expression was significantly lower in the comedo subtype than in the cribriform-micropapillary subtype. Again, the prevalence of pS2 protein expression in the solid subtype was intermediate between those of the other two subtypes. Our results suggest that DCIS is biologically heterogeneous with regard to such marker substances. This has possible implications for management of these lesions.
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  • 69
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 37 (1996), S. 299-302 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; occult ; color Doppler ; localization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Occult breast carcinoma presenting with axillary metastases is a difficult clinical problem. Mammography is recommended as the diagnostic tool for detecting breast masses, but is very insensitive. In two consecutive patients with nonpalpable carcinoma of the breast, the detection of breast lesions was made by color Doppler sonography. The sensitivity of the technique makes it a useful diagnostic aid in patients with negative mammograms.
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  • 70
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 38 (1996), S. 325-334 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; prognosis ; estrogen ; progestin ; HRT
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary We examined the influence of hormone replacement therapy (HRT) on breast tumour biology by comparing the prognostic characteristics of breast cancers and survival in 121 women prescribed replacement hormones before diagnosis with those in 1468 women without such treatment. The women receiving HRT had a lowered relative risk of being diagnosed with tumours of more than 20 mm in diameter, OR = 0.7 (CI 0.5–1.0) and axillary lymph node dissemination, OR = 0.7 (CI 0.4–1.1). These risk reductions were most pronounced and statistically significant in the women who had been prescribed a combined estradiol-progestin regimen. The patients in this compound group also had a diminished relative risk of having poorly differentiated tumours. Further, there was an indication that the women prescribed HRT, and especially those with conjugated estrogens/estradiols alone, had a decreased relative risk of developing aneuploid tumours. There was no clear pattern for women receiving the biologically weak oestriol, although risk estimates were generally higher for unfavourable tumours in comparison with those receiving the higher potency compounds. Adjustments for indications of earlier detection (i.e. lead time bias) did not influence the pattern or magnitude of the risk estimates. No association between any type of HRT and survival after breast cancer diagnosis was noted, but analyses were based only on 19 breast cancer deaths among exposed patients. We conclude that breast cancers occurring after treatment with HRT, especially the combined estrogen-progestin regimen, seem to have more favourable tumour features than tumours in non-treated women. Our findings may reflect a less aggressive biological behaviour of breast cancers in women receiving HRT, or in part be explained by the earlier detection of the tumours in these women.
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  • 71
    ISSN: 1573-7217
    Schlagwort(e): xenografts ; breast cancer ; cell lines ; resistance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The ability to maintain and study human tissues in anin vivo environment has proved to be a valuable tool in breast cancer research for several decades. The most widely studied tissues have been xenografts of established human breast cancer cell lines into athymic nude mice. Human breast tumor xenografts provide the opportunity to study various important interactions between the tumor and host tissues, including endocrinologic, immunologic, and tumor-stroma interactions. The nude mouse is not the only immune-deficient recipient system in which to study xenografts. Additional single and combined mutant strains have been used successfully, including mice homozygous for the severe combined immune deficiency mutation (scid), both the beige (bg) and nude (nu) mutations in combination (bg/nu), and mice bearing the combinedbg/nu/xid mutations. The differing immunobiologies are discussed, with particular reference to the immunobiology of breast cancer, as are the characteristics of several of the more frequently utilized breast cancer xenografts and cell lines. The ability of several endocrine treatments to modulate effectors of cell mediated immunity,e.g., estrogens and antiestrogens, and the effect of site of inoculation on tumor take and metastasis, also are described.
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  • 72
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; allelotype ; in situ hybridization ; paraffin sections
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary We have optimized a technique that allows the study of numerous chromosomal loci (n = 20–50) from single paraffin-embedded tissue sections by microsatellite length polymorphism analysis. DNA samples from normal and breast cancerous tissue can be obtained from the same section by means of microdissection. This technique was further improved by subjecting DNA to several cycles of amplification with a degenerate (universal) primer and then with specific microsatellite primers. This amplified DNA was also used to screen for mutations in the p53 gene by means of PCR-SSCP. In addition adjacent tissue sections were used to assess specific chromosome copy number by interphase cytogenetic analyses (chromosomein situ hybridization) and to analyze expression of specific genes such as p53 and ERBB2. As an example of the use of our approach we performed a detailed chromosome 17 allelotypic analysis in 22 breast tumors (5 ductal carcinomasin situ, 13 invasive ductal carcinomas, and 4 invasive lobular carcinomas). We detected mutations in the p53 gene by PCR-SSCP in 36% of the samples. Samples with significant levels of p53 protein accumulation detected by immunohistochemistry were also positive for mobility shifts in the SSCP analysis. We observed that chromosome 17 allelic losses and imbalance occurred at as early a stage as ductal carcinomain situ (DCIS). Although in some cases we observed allelic losses or imbalance affecting the 17p13 region, close to the p53 locus, several of the tumors showed dissociation between such loss or imbalance and p53 mutation. Lobular carcinomas were predominantly disomic for chromosome 17 in contrast with ductal tumors, which often showed polysomy for chromosome 17. This comprehensive approach correlating the tumor subtype, its allelotype, with specific chromosome copy number and specific gene mutations and expression in preinvasive or early invasive breast cancer lesions will potentially provide information of relevance for a better understanding of the multistep mechanisms of breast carcinogenesis.
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  • 73
    ISSN: 1573-7217
    Schlagwort(e): IGF-II ; breast cancer ; immunohistochemistry ; in situ hybridization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Insulin-like growth factor-II (IGF-II) is a potent mitogen for a variety of cell types and is considered an important regulator of breast cancer growth. In this study, we analyzed IGF-II mRNA and protein expression in a series of 80 cases of invasive breast cancer. Seventy-five cases produced informative results for IGF-II mRNA expression, and were scored on an arbitrary scale. Two cases (2.6%) had no significant IGF-II mRNA expression. 35 cases (46.7%) expressed low levels of IGF-II mRNA, 20 cases (26.7%) moderate IGF-II mRNA, while 18 (24%) expressed high levels of IGF-II message. Generally, IGF-II mRNA was expressed in the smooth muscle walls of blood vessels and ducts, as well as in the stroma tightly adjacent to and surrounding tumor epithelium. IGF-II mRNA content was also directly related to the amount of the stroma within the tumor (p〈0.05). In 10 cases (13.3%) IGF-II mRNA was detected in the stroma of normal lobules. Fifty-six out of 75 were positive for IGF-II immunostaining. Again, protein staining was generally observed in the smooth muscle of both blood vessels and ducts, as well as in the stroma surrounding tumor epithelium. In normal lobules and ducts the IGF-II protein was detected in the myoepithelium. Unequivocal IGF-II protein staining was seen in tumor epithelium in only three cases. The results of our study demonstrate that, in breast cancer, IGF-II mRNA is expressed in the smooth muscle and stromal components in the majority of invasive breast cancers. IGF-II expression correlates positively with the amount of stromal tissue present within a tumor. This suggests that IGF-II may have an important growth regulatory effect on breast tumor epithelium through paracrine pathways.
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  • 74
    ISSN: 1573-7217
    Schlagwort(e): antiestrogen ; breast cancer ; estrogen receptor ; estrogen-regulated genes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Effects of the pure antiestrogen ICI182780 and tamoxifen on ER-protein, ER-mRNA, and estrogen-regulated mRNA expression were analysed using matched pretreatment core-cut biopsies and post-treatment mastectomy samples from 43 ER positive human breast cancers. Sixteen controls received either no preoperative treatment (n = 9) (7 days) or placebo (n = 7) (median 21 days) prior to primary surgery. Nineteen patients received ICI182780 6 mg/day (n = 10) or 18 mg/day (n = 9) for 7 days. Eight patients were given preoperative tamoxifen (4 × 40 mg-day 1, 20 mg/day thereafter, median 21 days). ER-protein expression was assessed on pre and post treatment samples by immunocytochemistry. ER, pS2, pLIV1, and actin-mRNA expression was determined by northern analysis on post-treatment samples only. ER-mRNA levels were similar to controls following ICI182780 or tamoxifen treatment. However ER-protein levels were significantly suppressed by ICI182780, particularly at the higher dosage (p = 0.0013). Tamoxifen had no significant effect on ER-protein levels. The ER-mRNA and ER-protein contents of control tumors were linearly related (Spearman r = 0.719, p = 0.006). A similar relationship between pretreatment protein and post ICI182780 treatment mRNA levels was observed (r = 0.652, p = 0.005). However, comparison of post ICI182780 treatment protein and mRNA results shows a loss of linearity through a reduction in protein without concurrent loss of mRNA (r = 0.28, p = 0.257). pS2 mRNA hybridization was lower in ICI182780 treated samples than controls (Mann-Whitney p = 0.035) but was unaffected by tamoxifen. pLIV1 mRNA hybridization was uninfluenced by either treatment. Short term exposure of breast tumors to ICI182780 appears to produce a greater inhibition of estrogen-induced transcriptional events than tamoxifen. These effects appear to occur without a concurrent reduction in ER mRNA levels.
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  • 75
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; estrogen receptor ; inter-laboratory variation ; progesterone receptor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary All French laboratories that routinely assay estradiol (ER) and progesterone (PR) receptors participate in the European EORTC quality control program based on twice-yearly analysis of 5 cytosolic preparations. This system has considerably reduced inter-laboratory variations, but does not cover all aspects of these assays. Analysis of receptor value distributions is also crucial to ensure that receptor measurements remain stable with time, independently of the laboratory and assay method. This study involved 83907 receptor assays carried out in the last 17 years by 17 laboratories belonging to the French Study Group on Tissue and Molecular Biopathology. The assays were based on radioligand binding (RLA) or immunoenzymology (EIA). For each laboratory, the medians and positivity rates were analysed according to two totally objective criteria, the patient's age and the year of assay, and according to histological grade and histological type of the tumor in order to verify the correlations classically described. Age-related distributions varied little between laboratories, compared with data published by 7 European EORTC laboratories [1]. The results remained relatively stable with time in the RLA method for ER and PR, and in the EIA method for PR. Median ER-EIA data showed a marked increase between 1987 and 1989, mainly due to changes in the quality of Abbott reagents during this period. Otherwise, this analysis confirms previous pathophysiological observations.
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  • 76
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; immunosuppression ; lymphocytes ; p43
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary It has been previously shown that p43 — a breast cancer associated antigen — has immunosuppressive properties. The present study was carried out in order to elucidate the pathomechanisms of immunosuppression in breast cancer patients influenced by the expression of p43. Lymphocytes were cultured from blood of 29 women with benign lesions in the breast as well as from 41 female patients with breast cancer. Lymphocyte stimulation was performed by addition of Concanavalin (Con A) in cultures with lymphocytes alone (CONLYM) or in lymphocytes incubated with p43 (CONAg). In other series immunomodulation was tried by addition of indomethacin (INDLYM, INDAg), levamisole (LEVLYM, LEVAg), or interleukin-2 (ILLYM, ILAG). In breast cancer patients, addition of p43 significantly inhibited the activation of lymphocyte proliferation by Con A compared to women with benign tumors. The addition of indomethacin or levamisole did not influence this inhibitory effect of p43 in breast cancer patients. Contrary to these observations, addition of IL-2 resulted in increased proliferation of lymphocytes from patients with benign as well as malignant tumors, which was inhibited after addition of p43. Analysis of the correlation of the immunosuppressive properties of p43 in correlation with prognostic factors for breast cancer showed evidence for a stronger activity of p43 in early stage tumors (i.e. smaller than 2 cm, lymph node negative, histologic grading GI), confirming previous observations of a higher expression of p43 in early stages of breast cancer.
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  • 77
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; fibronectin ; invasion ; mouse mammary tumor model ; protease inhibitors ; treatment ; urokinase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Urokinase-type plasminogen activator (uPA) initiates an extracellular proteolytic cascade with which invasive cells eliminate barriers to movement. We have evaluated the antiinvasive and antimetastatic properties of two recently developed synthetic uPA inhibitors, B428 and B623, in a BALB/c mouse mammary carcinoma model. We used the F3II and M3 tumor cell lines, previously described by our laboratory.In vitro, noncytotoxic concentrations of B428 or B623 inhibited secreted and cell-associated uPA activity produced by tumor cells and blocked uPA-mediated whole tumor cell degradation of fibronectin, allowing deposition of extracellular fibronectin fibrils.In vivo, administration of compounds was not associated with overt toxic effects. Daily i.p. treatment with B428 (20 mg/kg/day) or B623 (7.5 mg/kg/day) for 2 weeks, beginning after tumor take, markedly blocked the invasion of the muscle and adipose layers of the subcutis and dermis in mice bearing highly invasive F3II tumors. However, these compounds neither inhibited tumor-induced angiogenesis nor reduced the incidence of spontaneous lung metastasis. Moreover, B623 enhanced the formation of experimental lung metastasis. Our results suggest that synthetic uPA inhibitors act as potent antiinvasiveness agentsin vivo but may be unable to control progression of the metastatic disease in the present mammary tumor model.
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  • 78
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 40 (1996), S. 225-230 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; male ; case series
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A review was conducted of 66 men with carcinoma of the breast seen at this institution between 1981 and 1992. The results of the study suggest that there are many similarities between breast cancer in men and women. The most common clinical presentation was a lump in the breast. The majority of tumors were T1 or T2, and infiltrating ductal carcinoma was the predominant histological type. Axillary nodal status and histological grade were predictive of survival. The pattern of recurrence and survival rates were similar to those seen in women. Some differences, however, were evident. Tumors were centrally located in the majority of patients and there was a high frequency of nipple involvement. The hormone receptor positivity rate was high and the median age at presentation was older. In comparison to a previous report of the same disease from this institution 10 years ago, fewer patients underwent radical surgical procedures and more patients received adjuvant systemic therapy. These approaches are justified since there are many biological similarities between breast cancer in men and women.
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  • 79
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; tumour markers ; serum c-erbB-2 ; ELISA ; prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The tissue expression of c-erbB-2 protein in breast cancer is a marker of poor prognosis in a number of studies. More recently it has also been suggested that c-erbB-2 expression may predict response to systemic therapy in patients with advanced breast cancer. The measurement of c-erbB-2 protein in the serum of breast cancer patients has now been reported, but the significance of this finding is not clear. In this study an ELISA assay was used to measure c-erbB-2 in the sera of 23 normal controls, 46 benign breast disease patients, and 119 breast cancer patients. Elevated serum c-erbB-2 protein levels were detected in 13% (3/23) of normal controls, 15% (7/46) of benign disease patients, 15% (7/46) of Stage I/II patients, 26% (9/35) of Stage III patients, and 21% (8/38) of Stage IV patients. The tissue expression of the c-erbB-2 protein showed no association with detection of the serum c-erbB-2 protein (p = 0.31). In the 67 Stage III and IV patients who had assessable disease the presence of the c-erbB-2 protein in the serum bore no relationship to response to hormonal therapy (p = 0.71). Serum detection of the c-erbB-2 protein in Stage I/II patients predicted for a worsening of both survival outcome (p = 0.002) and disease free interval (p = 0.002). A worse outcome was also seen for the Stage III patients (p = 0.04) and Stage IV patients, although the latter did not reach statistical significance (p = 0.27). This study found that the presence of c-erbB-2 in the serum of breast cancer patients was of prognostic significance for all stages of disease.
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  • 80
    ISSN: 1573-7217
    Schlagwort(e): amplicon ; breast cancer ; chromosome ; gene amplification ; polymerase chain reaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary A new method of measuring gene copy number in small samples of DNA was used to measure amplification of theerbB-2 gene and of chromosome 20q in breast cancers. This method, termed ‘differentially competitive polymerase chain reaction’ (DC-PCR) combines the advantages of two other techniques for measuring amplification by PCR, namely differential PCR and competitive PCR. The DC-PCR methodology was evaluated for sensitivity and specificity by comparing amplification oferbB-2 measured by DC-PCR with that obtained by fluorescencein situ hybridization (FISH) for 42 cases or Southern blotting and/or slot blot analysis for 34 cases. There was over 90 percent concordance with both FISH and Southern blotting and/or slot blot analysis. DC-PCR was used to further characterize the newly described amplicon at chromosome 20q. By analyzing DNA from 10 breast cancer cell lines at 7 different loci, we identified a potential common region of amplification of approximately 5 centimorgans at chromosome 20q13 bordered by loci D20S52 and RMC20C001-S1. One hundred and seventeen cases of primary breast cancer were evaluated for amplification at these two loci. Amplification at one or more loci, defined as 〉 1.5 fold higher copy number than that of normal DNA, was found in 25 cases (21%). Sixteen cases were amplified at only one of the two probes (12 cases for RMC20C001-S1 and 4 cases for D20S52), suggesting that the target gene lies between the two markers or that there are two independent target genes within a small chromosome region.
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  • 81
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; dot (slot) blot hybridization ; HPV DNA ; mammary Paget's disease ; Paget's disease ; PCR
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The paraffin sections from 20 nipples with Paget's disease (10 central intraductal and 10 invasive ductal carcinomas) were analyzed for human papilloma virus (HPV) DNA of the low- and intermediate/high-risk groups. Polymerase chain reaction (PCR) and dot (slot) blot hybridization were used for the detection of HPV DNA types 6/11/16/18/31/33/35. In addition, we examined the c-erbB-2 oncogene expression in the specimens to differentiate benign cells in the surface epithelium of the nipple and areola from Paget cells. We found that the oncogene expression of the c-erbB-2 displayed a strong signal in the Paget cells. Using PCR and dot (slot) blot hybridization, we could not detect the HPV DNAs that are specific for the low- and intermediate/high riskgroups in the 20 cases of Paget's disease. Our results showed for the first time that this type of virus did not contribute to the pathogenesis of Paget's disease.
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  • 82
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; Gail model ; prevention ; risk factors ; risk perception ; screening
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The Gail model is being used increasingly to determine individual breast cancer risk and to tailor preventive health recommendations accordingly. Although widely known to the medical and biostatistical communities, the risk factors included in the model may not be salient to the women to whom the model is being applied. This study explored the relationship of the individual Gail model risk factors to perceived risk of breast cancer and prior breast cancer screening among women with a family history of breast cancer. Data from baseline interviews with 969 women found a striking disparity between the objective risk factors included in the model and the accuracy of perceived risk and screening behaviors of this population, particularly among women over the age of 50 years. Risk perception accuracy was unrelated to all of the Gail model risk factors for all age groups. Reported mammography adherence was only associated with having had a breast biopsy in both age groups. Breast self examination (BSE) practice was independent of all measured factors for both age groups. These findings support the need for further research to identify additional determinants of risk perception and motivators of screening behavior.
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  • 83
    ISSN: 1573-7225
    Schlagwort(e): Anthropometry ; breast cancer ; elbow width ; height ; menopause ; metabolic rate ; risk factors ; United States
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: To investigate whether cancer risk-reduction seen in calorie-restricted animals also applies to breast cancer in women, we have analyzed data from the first National Health and Nutrition Examination Survey in the United States and subsequent follow-up surveys. During the follow-up of one to 155 months, 182 out of 7,622 women developed breast cancer. Due to biased under-reporting of dietary intake, the analysis did not examine calorie intake as an exposure variable, but rather focused on anthropometric measures and metabolic rate as biomarkers of nutritional balance. Multiple Cox regression analysis showed elevated odds ratios (OR) for height, elbow width, and skinfolds among postmenopausal women. ORs for the fifth quintile were 2.0 (95 percent confidence interval [CI]=1.0–3.8), 2.3 (CI=1.2–4.7), and 2.0 (CI=1.0–4.0), respectively. Weight (OR=2.5, CI=1.2–5.1) and resting metabolic rate (OR=2.0, CI=1.0–4.0) were significant relative to the second quintile. Bitrochanteric breadth, sitting height, body fat, body mass index, or combination variables were not associated with cancer risk. It was concluded that in the analysis of breast cancer data, skeletal measures ought to be considered as routine potential confounders, and that using measured rather than estimated metabolic rates may improve risk prediction.
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  • 84
    ISSN: 1573-7225
    Schlagwort(e): α-tocopherol ; breast adipose tissue ; breast cancer ; Finland ; vitamin E
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Previous data on animals and humans suggest that vitamin E may be a protective factor against cancer. A low dietary vitamin E intake has been suggested to increase the risk of breast cancer. We examined the dietary intake and the concentration of vitamin E in breast adipose tissue of women in Kuopio, Finland, diagnosed between 1990 and 1992 with benign breast disease (n=34) and with breast cancer (n=32). In postmenopausal women, lower dietary intake (P=0.006) and a smaller concentration of vitamin E in breast adipose tissue (P=0.024) were observed in breast cancer patients than in subjects with benign breast disease. Partial correlation showed that the vitamin E concentration in the breast adipose tissue correlated positively with the dietary intake of vitamin E (r=0.25, P=0.023), indicating that the vitamin E concentration in breast adipose tissue reflects the dietary intake of vitamin E.
    Materialart: Digitale Medien
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  • 85
    ISSN: 1573-7276
    Schlagwort(e): breast cancer ; invasion ; invasion-inhibiting factor 2 ; metastasis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Invasion-inhibiting factor 2 (IIF-2) and its albumin conjugate have been reported to inhibit spontaneous metastasis of highly metastatic cancer cells with no effect on primary tumor growth. To confirm the inhibitory effects of the IIF-2 conjugate on tumor invasion and spontaneous metastasis, we administered the conjugate intra-peritoneally (i.p.) to female nude mice bearing transplanted tumors with MKL-4 cells, which are MCF-7 human breast cancer cells cotransfected with fibroblast growth factor 4 and lacZ. Neither 10 nor 20 mg/kg doses of the conjugate caused any inhibition of primary tumor growth, but 20 mg/kg significantly inhibited tumor invasion and spontaneous metastasis. Tumor invasion was measured by a novel computer-assisted image analysis. Spontaneous microscopic metastases into lymph nodes and distant organs were measured by whole organ staining for ß-galactosidase activity and observed with a dissecting microscope. The dose of 10 mg/kg significantly inhibited tumor invasion but not metastasis. Interestingly, the number of factor VIII-positive microvessels in the tumors was not reduced by treatment at either dose level. These findings suggest that the anti-invasive effect of the IIF-2 conjugate may reduce both lymphatic and hematogenous metastases in this MKL-4 metastasis model without affecting angiogenesis.
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  • 86
    ISSN: 1573-7276
    Schlagwort(e): breast cancer ; invasion ; metalloproteinase ; linoleic acid ; 12-hydroxyeicosatetraenoic acid
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Diets rich in linoleic acid (LA) stimulate the metastasis of MDA-MB-435 human breast cancer cells from the mammary fat pads of nude mice. This omega-6 fatty acid is metabolized to various cyclo-oxygenase and lipoxygenase products, several of which have been previously associated with tumor cell invasion and metastasis. We now report that MDA-MB-435 cells secreted increased levels of prostaglandin E2 (PGE2), and 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE when cultured in the presence of 2.7 µm (0.75 µg/ml) LA; 5-HETE secretion was unchanged. The 12-lipoxygenase inhibitor esculetin (20 µM) completely blocked the LA-stimulated 12-HETE secretion. Linoleic acid also increased MDA-MB-435 cell invasion in an in vitro assay; this stimulation was abolished by 20 µM esculetin, but was unaffected by piroxicam, a selective cyclooxygenase inhibitor. The effect of LA on invasion was replicated by 0.1 µM 12-HETE, but not by 5-HETE or PGE2; 15-HETE was stimulatory only at a concentration of 1.0 µm. Zymographic and Northern blot analyses showed that these events are accompanied by the induction of 92 kDa isoform type IV collagenase (metalloproteinase-9) enzymic activity and mRNA expression by exogenous LA and 12-HETE, and their suppression by the 12-lipoxygenase inhibitor. These results suggest that the effects of dietary LA on breast cancer cell metastasis in the nude mouse model are due, at least in part, to enhanced 12-HETE biosynthesis, with an associated increase in proteolytic enzyme activity and tumor cell invasiveness.
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  • 87
    Digitale Medien
    Digitale Medien
    Springer
    Journal of bone and mineral metabolism 14 (1996), S. 1-9 
    ISSN: 1435-5604
    Schlagwort(e): estrogen ; raloxifene ; bone ; uterus ; breast cancer ; cholesterol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In view of its highly tissue-selective pharmacological properties (i.e., relatively pure antagonist in reproductive tissue with minimal agonist effects to nearly full agonist properties in bone and on cholesterol metabolism), terms used to define compounds with slightly related pharmacology (i.e., antiestrogen, partial estrogen agonist) do not adequately describe raloxifene's activity. Thus, raloxifene is distinct from agents such as tamoxifen (which does stimulate the uterus), or frank estrogen (which do not sufficiently antagonize estrogen's agonistic effects in reproductive tissue). In this regard, raloxifene and its pyrrolidine analogue, LY117018, (81) are the first representatives of a novel class of pharmacological agents, which we have termed “selective estrogen receptor modulator” (SERM). While we now have considerable evidence to distinguish estrogen recepto-mediated effects on bone from those on reproductive tissue, the precise mechanism for this tissue-specific mechanism remains an active area of investigation. Clearly, many important issues remain to be explored.
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  • 88
    Digitale Medien
    Digitale Medien
    Springer
    Journal of clinical psychology in medical settings 3 (1996), S. 185-199 
    ISSN: 1573-3572
    Schlagwort(e): breast cancer ; family history ; risk perception ; cancer concern ; screening practices
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Many women with family histories of breast cancer deal with two distinct but related issues: their objective physical risk and the emotions this risk engenders. Studies indicate that approximately 70% of African American and white women are concerned about their chances of developing breast cancer someday and perceive themselves to be at risk. Health care providers, including psychologists, need to be aware of the special needs and psychosocial concerns of high-risk women with family histories of breast cancer, since perceptions of breast cancer risk influence screening practices. Providers need training in understanding the significance of specific family patterns of breast cancer, screening guidelines appropriate for women at risk, and the benefits and risks of available prevention options, including genetic screening. Delivering accurate information about both established risk factors known to elevate personal risk, such as age and family history, and factors which women associate with breast cancer, such as bumping and bruising a breast, smoking, and oral contraceptive use, is essential for promoting accurate risk perceptions and appropriate screening schedules.
    Materialart: Digitale Medien
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  • 89
    Digitale Medien
    Digitale Medien
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 62 (1996), S. 102-112 
    ISSN: 0730-2312
    Schlagwort(e): NDF ; estrogen receptor ; breast cancer ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Most human breast tumors start as estrogen-dependent, but during the course of the disease become refractory to hormone therapy. The transition of breast tumors from estrogen dependent to independent behavior may be regulated by autocrine and/or paracrine growth factor(s) that are independent of the estrogen receptor (ER). We have investigated the role(s) of NDF (neu-differentiation factor) in the biology of estrogen positive breast cancer cells by using MCF-7 cells as a model system. Treatment of MCF-7 cells with human recombinant NDF-β2 (NDF) inhibited the ER expression by 70% and this was associated with growth stimulation in an estrogen-independent manner. To explore the mechanism(s) of action of NDF in MCF-7 cells, we examined the expression of NDF-inducible gene products. We report here that NDF stimulated the levels of expression of a 46 kD protein (p46) (in addition to few minor proteins) in ER positive breast cancer cells including MCF-7, T-47-D, and ZR-75-R cells but not in ER negative breast cancer cells including MDA-231, SK-BP-3, and MDA-468 cells. This effect of NDF was due to induction in the rate of synthesis of new p46. The observed NDF-mediated induction of p46 expression was specific as there was no such effect by epidermal growth factor or 17-β-estradiol, and inclusion of actinomycin D partially inhibited the p46 induction elicited by NDF. NDF-inducible stimulation of p46 expression was an early event (2-6 h) which preceded the period of down-regulation of ER expression by NDF. These results support the existence of NDF-responsive specific cellular pathway(s) that may regulate ER, and these interactions could play a role(s) in hormone-independence of ER positive breast cancer cells. © 1996 Wiley-Liss, Inc.
    Zusätzliches Material: 8 Ill.
    Materialart: Digitale Medien
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  • 90
    Digitale Medien
    Digitale Medien
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 63 (1996), S. 112-122 
    ISSN: 0730-2312
    Schlagwort(e): biomarkers ; breast cancer ; chemoprevention ; high-risk ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: In a prospective pilot study, we performed breast fine needle aspirations (FNAs) on 213 high-risk and 30 low-risk women and analyzed these aspirates for cytologic changes and biomarker abnormalities of aneuploidy and overexpressed estrogen receptor (ER), epidermal growth factor receptor (EGFR), p53 and HER-2/neu. High-risk women were those with a first degree relative with breast cancer (73%), prior biopsy indicating premalignant breast disease (26%), a history of breast cancer (13%), or some multiple of these risk factors (11%). Median ages of the high-risk and low-risk groups were 44 and 42, respectively. Sixty-three percent of the high-risk and 73% of the low-risk group were premenopausal. Sixty-eight percent of the high-risk and 17% of low-risk women had cytologic evidence of hyperplasia with or without atypia (P 〈 .0001). Aneuploidy and overexpression of EGFR and p53 occurred in 25%, 36%, and 28% of high-risk subjects but in less than 4% of low-risk subjects (P 〈 .0002). Overexpression of ER and HER-2/neu occurred in 8% and 19%, respectively of high-risk women; no low-risk women had these abnormalities. Sixty-eight percent of high-risk women and 7% of low-risk women had abnormalities of one or more of these biomarkers exclusive of cytology. Thirty-one percent of high-risk women, but no low-risk women had abnormalities of two or more biomarkers (P = .0004). Biomarker abnormalities were more frequent with increasing cytologic abnormality. Eighteen percent of women with normal cytology, 29% of women with epithelial hyperplasia and 60% of women with hyperplasia with atypia had abnormalities of two or more biomarkers (P = .048 and 〈 .0001, respectively). Restricting the analysis to those three biomarkers most frequently overexpressed in the high-risk group (ploidy, EGFR, p53), 13% of high-risk women with normal cytology, 20% of high-risk women with epithelial hyperplasia and 51% of high-risk women with atypical hyperplasia had abnormalities of 2 or more of these 3 biomarkers. At a median follow up of two years, 8 of 213 women have been diagnosed with in situ (n = 5) or invasive (n = 3) cancer. Later detection of neoplasia was associated with prior FNA evidence of atypical hyperplasia (P 〈 .0001) and multiple biomarker abnormalities in the 5 test battery (P = .006) by univariate analysis. By multivariate analysis, development and/or detection of cancer was primarily predicted by atypical hyperplasia (P = .0047) and secondarily by multiple biomarker abnormalities (P = 0.021). Atypical hyperplasia, EGFR, and p53 in breast FNAs have promise as risk markers and as surrogate endpoint biomarkers for breast cancer chemoprevention trials. J. Cell. Biochem. 25S:112-122. © 1997 Wiley-Liss, Inc.
    Zusätzliches Material: 3 Ill.
    Materialart: Digitale Medien
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  • 91
    Digitale Medien
    Digitale Medien
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 63 (1996), S. 174-184 
    ISSN: 0730-2312
    Schlagwort(e): cytokeratins ; hormone independence ; T-47D5 ; nuclear matrix ; breast cancer ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: The tissue matrix consists of linkages and interactions of the nuclear matrix, cytoskeleton, and extracellular matrix. This system is a dynamic structural component of the cell that organizes and processes structural and functional information to maintain and coordinate cell function and gene expression. We have studied estrogen regulation of nuclear matrix associated proteins, including the intimately connected cytoskeletal intermediate filaments, in T-47D5 human breast cancer cells. Three proteins (identified as cytokeratins 8, 18, and 19) present in the nuclear matrix-intermediate filament fraction (NM-IF) of cells grown in estrogen-replete conditions were dramatically reduced when the cells were grown in acute (1 week) estrogen-depleted conditions. Replacing estrogen in the medium of acute estrogen-depleted cells restored expression of these proteins. T-47D5 cells that are chronically depleted of estrogen (T5-PRF) are estrogen-nonresponsive in culture. These cells overexpressed these three proteins, compared to parent cells grown in the presence of estrogen. Treatment of the T5-PRF cells with estrogen did not lead to further up-regulation of these proteins. Treating T-47D5 cells in estrogen-replete conditions with the antiestrogens 4-hydroxytamoxifen and ICI 164 384 (100 nM, 3 days) resulted in a significant reduction in these proteins, while no effect was seen in long-term chronic estrogen-depleted T-47D5 cells. In conclusion, we have identified NM-IF proteins (cytokeratins 8, 18, and 19) in human breast cancer cells that are estrogen regulated and may play a role in estrogen action in human breast cancer cells. © 1996 Wiley-Liss, Inc.
    Zusätzliches Material: 8 Ill.
    Materialart: Digitale Medien
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  • 92
    Digitale Medien
    Digitale Medien
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 63 (1996), S. 15-22 
    ISSN: 0730-2312
    Schlagwort(e): bladder cancer ; breast cancer ; ethnicity ; polymorphism prostate cancer ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: The past four decades of epidemiological research have yielded valuable information on the risks of populations to environmental exposures such as tobacco, asbestos, and dietary components. Prevention efforts have been focused on large-scale population-based interventions to minimize exposure to such external carcinogens. While some cancers are beginning to show a decline from changing environmental exposures, hormone-related cancers, such as breast and prostate, are becoming more prevalent. The development of these cancers appears to be closely related to endogenous exposures to circulating steroid hormones. Although prevention trials using antihormone agents are proving successful in some instances, the long-term control of these cancers necessitates a clearer understanding of the metabolism and transport of the relevant hormone in vivo.The revolution in molecular biology has provided powerful genetic tools for evaluating mechanisms of cancer causation as well as the potential to better define individual susceptibility. Using tobacco exposure as an example, we and others have demonstrated that polymorphisms in genes controlling aromatic amine metabolism provide at least a partial explanation for ethnic and individual susceptibility to bladder cancer. Similar studies have examined genetic polymorphisms in the metabolism of tobacco smoke and lung cancer risk, red meat and colorectal cancer, and aflatoxin and liver cancer.Our current studies have pursued a similar paradigm of genetic polymorphism and individual cancer susceptibility in prostate and breast carcinogenesis. We are evaluating polymorphisms in the steroid 5α-reductase type II and androgen receptor genes in relation to prostate cancer based on the evidence that intracellular dihydrotestosterone is the critical “carcinogen.” We are pursuing genetic polymorphisms affecting estradiol metabolism, including those in the 17β-hydroxysteroid dehydrogenase 2 and estrogen receptor genes as they relate to susceptibility to breast cancer. The potential role of a polymorphism in the cytochrome P450c17α gene in both breast and prostate cancers is also being examined. J. Cell. Biochem. 25S:15-22. © 1997 Wiley-Liss, Inc.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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