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  • 11
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 246 (1973), S. 352-355 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] In these studies, hepatoma tissue culture (HTC) cells and mouse fibroblasts (L cells) were grown in tissue culture and collected by standard methods5'6. Both HTC7 and L cells8 have high affinity cytoplasmic receptor molecules and there is considerable evidence to implicate these proteins in the ...
    Type of Medium: Electronic Resource
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  • 12
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Quarante-trois malades qui présentaient un cancer du sein avancé (15 répondant au stade IIIA et 28 au stade IIIB) ont été traitées par chimiothérapie et chez 38 d'entre elles par hormonothérapie associée pour obtenir une involution tumorale avant de procéder au traitement local. Lorsque la réponse à ce traitement fut complété (CR) la radiothérapie fut associée à la chimiothérapie. Quand la réponse fut incomplète (PR = réponse partielle) ou négative (NC = pas de changement) l'intervention chirurgicale fut pratiquée et suivie d'une irradiation locale. Chez toutes les malades la chimiothérapie fut ensuite poursuivie pendant 6 mois. La chimiothérapie consista en l'administration de cyclophosphamide 500 mg/m2; de doxorubicine 30 mg/m2 I.V. au jour 1; de tamoxifen: 40 mg/m2 P.O. les jours 2–6; de premarine 0.625 mg P.O. Q 12×3h à partir du 71ème jour, de méthotrexate: 300 mg/m2 I.V. suivi après 1 heure par du 5-fluorouracil 500 mg/m2 par voie I.V. au jour 8 et de leucovirine 10 mg/m2 P.O. Q 6h×6 commençant 24 h après le méthotrexate. Quarante-deux malades sur 43 purent être soumises à l'étude en ce qui concerne la réponse au traitement, le temps d'évolution et la survie. Le taux de la réponse à l'action des agents chimiques fut le suivant: involution complète, 50%; involution partielle, 40%; inefficacité 10%. Le nombre médian de cycles de chimiothérapie pour aboutir à ces résultats fut respectivement de 5,4 et 4. Dix-huit malades qui bénéficièrent d'une involution clinique tumorale complète furent soumises à des biopsies multiples (16) ou à une mastectomie (2). Quatorze malades (70%) ne présentaient aucune trace tumorale à l'examen histologique. Trente malades sur 42 qui ont été soumises au traitement combiné complet ne présentent à ce jour aucun signe d'évolution du processus tumoral. Les malades du stade IIIA n'ont pas montré de récidive. En revanche 7 cas de stade IIIB ont rechuté, 6 d'entre eux montrant des lésions inflammatoires à l'histologie. Pour chaque stade la survie médiane et le temps d'évolution n'ont pu être apprécié au cours de cette étude.
    Abstract: Resumen Cuarenta y tres pacientes con cáncer mamario localmente avanzado, 15 en estado IIIA y 28 en estado IIIB, recibieron quimioterapia primaria de inducción, incluyendo sincronización hormonal en 38 pacientes, hasta el logro de una respuesta clínica objetiva máxima antes de proceder con terapia local. Las pacientes que lograron una respuesta completa desde el punto de vista histológico (múltiples biopsias sobre el lugar de la lesión original) recibieron radioterapia, mientras las pacientes con enfermedad residual (respuesta parcial o ninguna respuesta) fueron sometidas a cirugía de “debultamiento” antes de iniciar la radioterapia; en la totalidad de las pacientes se administraron 6 meses adicionales de quimioterapia. La quimioterapia consistió en ciclofosfamida 500 mg/m2 y doxorubicina 30 mg/m2 I.V. el día 1; tamoxifén 40 mg/m2 PO en los días 2–6; premarina 0.625 mg PO q 12 horas × 3, comenzando en el día 7; metotrexato (mtx) 300 mg/m2 I.V. seguido una hora después de 5-fluoruracilo 500 mg/m2 I.V. el día 8 y leucovorin 10 mg/m2 PO q 6 horas × 6 comenzando 24 horas después del mtx. Cuarenta y dos pacientes son evaluables en relación a la respuesta lograda, al tiempo de progresión y a la supervivencia. La tasa de respuesta objetiva a la quimioterapia fue de 90% con 50% de respuesta completa, 40% de respuesta parcial y 10% de ninguna respuesta. El número promedio de ciclos de quimioterapia necesarios para lograr respuesta completa, respuesta parcial o ninguna respuesta fue de 5, 4, y 4 respectivamente. Dieciocho pacientes con respuesta completa a la quimioterapia fueron evaluadas mediante biopias múltiples (16 pacientes) o mastecomía (2 pacientes). Catorce (70%) demostraron respuesta completa desde el punto de vista histológico. Treinta pacientes han completado terapia combinada hasta el momento y todas se han convertido a un estado libre de enfermedad. Siete pacientes en estado IIIB han presentado recurrencia, 6 de ellas con histología de enfermedad tumoral inflamatoria. Ninguna paciente en estado IIIA ha presentado recurrencia. No se ha llegado todavía a determinar la supervivencia media ni el tiempo de progresión para ninguno de los estados.
    Notes: Abstract Forty-three patients with locally advanced breast cancer, 15 with stage IIIA and 28 with stage IIIB, received primary induction chemotherapy, including hormonal synchronization in 38 patients, to a maximum objective clinical response before proceeding to local therapy. Patients achieving a pathological complete response received radiation therapy, while patients with residual disease, partial response (PR), or no change (NC) status received debulking surgery prior to radiation therapy; in all patients, 6 additional months of chemotherapy were administered. Chemotherapy consisted of cyclophosphamide 500 mg/m2 and doxorubicin 30 mg/m2 intravenously day 1; tamoxifen 40 mg/m2 orally days 2–6; premarin 0.625 mg orally every 12 hours 3 times beginning on day 7; methotrexate (mtx) 300 mg/m2 intravenously followed in 1 hour by 5-fluorouracil 500 mg/m2 intravenously day 8, and leucovorin 10 mg/m2 orally every 6 hours 6 times beginning 24 hours after mtx. Forty-two patients are evaluable with respect to response, time to progression, and survival. Objective response rate to chemotherapy was 90% with 50% CR, 40% PR, and 10% NC. Median number of cycles of chemotherapy to achieve a CR, PR, or NC was 5, 4, and 4 respectively. Eighteen patients with a CR to chemotherapy were assessed by multiple biopsies (16 patients) or mastectomy (2 patients). Fourteen patients (70%) were proven to be pathological complete responders. Thirty patients have completed combined therapy thus far and all have been rendered disease free. Seven stage IIIB patients have relapsed, 6 of them having inflammatory histological findings. No stage IIIA patients have relapsed. Median survival and time to progression have not been reached for either stage.
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  • 13
    ISSN: 1573-7217
    Keywords: fibroblast growth factors ; beta-galactosidase ; hormone dependence ; metastasis ; AGM 1470 ; pentosan polysulfate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Progression of breast cancer from an estrogen-dependent, slowly growing tumor amenable to tamoxifen treatment to an aggressive, metastatic, estrogen-independent phenotype has been mimicked by the transfection of MCF-7 breast carcinoma cells with fibroblast growth factors 1 or 4. FGF-transfected cells are aggressively tumorigenic in ovariectomized or tamoxifen-treated nude mice, conditions under which the parental cells would not produce tumors. When detection of metastasis was enhanced bylacZ transfection, the FGF-transfected MCF-7 cells were reliably metastatic to lymph nodes and frequently metastatic to lungs, in further contrast to parental cells. An antiangiogenic drug, AGM-1470, given to mice bearing tumors produced by FGF-transfected MCF-7 cells, produced a decrease in tumor size. The decreased tumor size was not as marked as that produced by treatment with pentosan polysulfate, an agent which would abrogate all autocrine or paracrine effects of the transfected FGF. Thus, increased angiogenesis may be a component of the phenotypic change produced by the FGF transfection, but other autocrine or paracrine effects may also be important. Since a clonal FGF-4 andlacZ doubly-transfected cell line, MKL-4, progressively lost expression of the transfectedlacZ gene in individual cells, we performed successive rounds of fluorescence-activated cell sorting to select high-expressing cells. High-expressing cell populations thus obtained rapidly lost expression of ß-gal activity in continued culture. High ß-gal expressing clonal cell lines of MKL-4 cells established by either one or two rounds of low-density cloning also lostlacZ expression with continued culture. Southern analysis of DNA fromlacZ transfected cell lines showed the transfected sequences to be present and grossly intact in both high and low expressing populations. However, Northern analysis revealed that high-expressing populations of MKL-4 cells contained the mostlacZ mRNA, implying that in the unstable MKL-4 cell line, individual cells are down-regulating mRNA levels oflacZ. StablelacZ expression has been obtained in other FGF-transfected and parental MCF-7 cell lines using the same expression vector. Thus, the MKL-4 cell line is down-regulating mRNA encoding the transfected gene through a mechanism not dependent on the CMV promotor utilized in the expression vector. This evidence suggests thatlacZ expression is not a benign modification in certain cells.
    Type of Medium: Electronic Resource
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 4 (1984), S. 251-259 
    ISSN: 1573-7217
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 15
    ISSN: 1573-7217
    Keywords: tamoxifen ; fluoxymesterone ; danazol ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A prospective randomized trial of tamoxifen and fluoxymesterone versus tamoxifen and danazol in metastatic breast cancer was conducted from December 1980 to September 1985. Patients were eligible regardless of site of disease, estrogen receptor status, or age. Sixty-two of sixty-three randomized patients were evaluable for response. Overall response for tamoxifen and fluoxymesterone was 11% with 61% stabilization of disease, versus 12% response rate for tamoxifen and danazol with 59% stabilization. Toxicities with tamoxifen and fluoxymesterone were greater with an increase in masculinization. We conclude that the response rates to the combinations of tamoxifen and fluoxymesterone or tamoxifen and danazol reported are equivalent in this study but that the increased toxicity with tamoxifen and fluoxymesterone would make tamoxifen and danazol the treatment of choice if a combination were to be used.
    Type of Medium: Electronic Resource
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 29 (1994), S. 141-160 
    ISSN: 1573-7217
    Keywords: psychosocial factors ; dietary fat ; alcohol ; prevention ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The factors responsible for the genesis of breast cancer remain unclear. Emerging, although controversial, evidence suggests that factors related to life-style, such as dietary fat or alcohol intake, or exposure to various forms of stressors, are associated with mammary tumorigenesis. The possible role of life-style factors in breast cancer is important in light of the fact that mortality to this disease is increasing in most countries and that development of curative therapies for breast cancer has not been forthcoming. Thus, determining the role of life-style factors in the onset and progression of breast cancer, particularly among individuals genetically vulnerable to breast cancer or women with breast cancer in remission, is critical to prevent this disease. We will review the three main hypotheses which have been suggested to link psychosocial factors to the etiology of cancer, emphasizing data obtained through animal models. Interpretation of the existing data suggests that the number of stressful life-events does not predict vulnerability to develop breast cancer or survival from it; a certain level of stress appears to protect from malignancies. The crucial factor affecting tumor growth is the interaction among stress, an individual's personality, and available psychosocial support, and the effect of this interaction on an individual's ability to cope with stress. In addition, other risk factors for breast cancer known to be closely associated with psychosocial factors, namely dietary fat and alcohol consumption, may interact with the effects of psychosocial factors on breast cancer.
    Type of Medium: Electronic Resource
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  • 17
    ISSN: 1573-7217
    Keywords: breast cancer ; insulin ; lipids ; MCF-7 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Stimulation of lipid synthesis by insulin in MCF-7 human breast cancer cells is characterized by an increase in acetate incorporation into long-chain fatty acids. The effects occurs in the absence of an increase in glucose uptake by the cells, and cannot be explained by a decrease in turnover of cellular fatty acids. Differential substrate experiments as well as direct measurement of enzyme activities indicate that insulin stimulates increases in activity of the first enzyme of the de novo pathway, acetyl CoA carboxylase. [3 2Pi] incorporation into phospholipids is also stimulated by insulin. Thin layer chromatography reveals five peaks of [3 2Pi]-labeled phospholipids corresponding in mobility to the following standards: lysophosphatidylcholine, sphingomyelin, phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine. [3 2Pi] incorporation into each of these peaks is stimulated, although the degree of stimulation varies.
    Type of Medium: Electronic Resource
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  • 18
    ISSN: 1573-7217
    Keywords: breast cancer ; excisional biopsy ; mastectomy ; psychosocial outcome ; radiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thirty-eight patients treated for primary breast cancer as part of a prospective randomized clinical trial were questioned retrospectively as to their psychosocial adaptation to treatment. Twenty patients had received mastectomy and eighteen had received excisional biopsy plus radiation of the intact breast. Aside from body image concerns, there were no marked psychosocial differences detected between these groups. Previous studies emphasizing serious psychological problems in mastectomy patients and fewer such problems in nonmastectomy patients may be influenced by biases that are not present in a randomized study design.
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  • 19
    ISSN: 1573-7217
    Keywords: antiestrogen ; autocrine growth factors ; EGF ; hormone dependence ; IGF-I ; paracrine growth factors ; PDGF ; TGFα ; TGFβ
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We consider the hypothesis that estrogen control of hormone dependent breast cancer is mediated by autocrine and paracrine growth factors secreted by the breast cancer cells themselves. Though we show direct, unmediated effects of estrogen on specific cell functions, we also provide evidence that human breast cancer cells secrete a collection of growth factors (IGF-I, TGFα, TGFβ, a PDGF-like competency factor, and at least one new epithelial colony stimulating factor). Some of these are estrogen-regulated in hormone dependent cells, and are constitutively increased in cells which acquire independence either spontaneously or byras transfection. Collectively, the secreted growth factors are capable of promoting tumor formation by MCF-7 cells in nude mice, though not to the same extent as estrogens. There would seem to be potential for clinical intervention in the autocrine and paracrine control of breast cancer cells, including some cells which are no longer dependent on estrogens.
    Type of Medium: Electronic Resource
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  • 20
    ISSN: 1573-7217
    Keywords: breast cancer ; conservation treatment ; local excision ; mastectomy ; radiotherapy ; rehabilitation ; surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent data suggest that prognosis is similar for women with primary breast cancer whether they receive modified radical mastectomy (MRM) or local excision and axillary dissection with radiation (XRT). The effects of either of these treatments on arm mobility, pain, or edema have not been compared. To assess the impact of MRM or XRT on mobility, pain, or edema, we evaluated patients treated in a prospective randomized trial designed to assess prognosis following MRM or XRT. All were provided a standardized physical therapy program including arm mobilization, shoulder strengthening, prevention and treatment of upper extremity edema, and education about arm function. Patients were evaluated for chest wall pain, arm motion, muscle strength, and edema as determined by circumferential measurements at the wrist, forearm, and arm. Evaluations were performed preoperatively and at yearly anniversaries of their surgery. Women receiving XRT had more chest wall tenderness at 1 and 2 years after surgery than those receiving MRM (p2〈0.0001 and p2=0.0007 respectively). Those receiving MRM were slower to reach their preoperative range of motion (ROM) (p2=0.043). Incidence of muscle weakness was similar in both groups. The few patients with local recurrence of tumor had more upper extremity edema than those who did not recur (p2=0.085) at 1 year and (p2=0.02) at 2 years. In patients who did not develop local recurrence, those who had received XRT had greater but nonsignificant increases in upper extremity circumferential measures compared with those receiving MRM at any anniversary evaluation. Patients receiving MRM and XRT are likely to have some differences in functional outcome. These differences may be important to individuals and be significant in helping them choose between MRM and XRT based upon individual functional needs.
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