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  • 1
    Electronic Resource
    Electronic Resource
    Fibroblast growth factor overexpressing breast carcinoma cells as models of angiogenesis and metastasis (1996)
    Springer
    Breast cancer research and treatment 39 (1996), S. 103-117 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF01806082
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  • 2
    Electronic Resource
    Electronic Resource
    Inhibition of tumor growth and metastasis by angiogenesis inhibitor TNP-470 on breast cancer cell lines in vitro and in vivo (1997)
    Springer
    Breast cancer research and treatment 45 (1997), S. 15-27 
    Details
    ISSN: 1573-7217
    Keywords: angiogenesis inhibitor ; breast cancer ; mammary tumor ; metastasis ; TNP-470
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Antitumor and antimetastatic activity of the angiogenesis inhibitor O-(chloroacetyl-carbamoyl) fumagillol (TNP-470), a semisynthetic analogue offumagillin, was evaluated in breast cancer cell lines. In an in vitro MTTassay, after 72 hrs continuous exposure to TNP-470, growth inhibition wasobserved in all seven cell lines of murine (JYG-A, JYG-B, DD-762, andBALB/c-MC) or human (KPL-1, MDA-MB-231, and MKL-F) origin, in which the50% inhibitory concentrations (IC50) at 72 hrstreatment were 4.6, 4.4, 4.6, 10.1, 35.0, 25.3, and 33.4 µg/ml,respectively. In an in vivo assay using JYG-A, JYG-B, KPL-1, and MDA-MB-231cells by orthotopic (right thoracic mammary fat pad) transplantation infemale nude mice, TNP-470 at 30 or 50 mg/kg body weight was injected s.c.every other day from the day of tumor cell inoculation until the end of theexperiment. The inhibitory effect on primary tumor growth was obtained inall four cell lines in a dose-dependent manner. In the 50 mg/kgTNP-470-treated group, the reductions in tumor weight of the JYG-A, JYG-B,KPL-1, and MDA-MB-231 cells with respect to the controls were 50%,30%, 4%, and 49%, respectively. Metastasis was seen inthe JYG-A, JYG-B, and KPL-1 cells. The numbers of mice bearing pulmonarymetastases of JYG-A and JYG-B cells and regional axillary lymph nodemetastases of KPL-1 cells were reduced, and TNP-470 at the 50 mg/kg dose toKPL-1 cells significantly reduced lymph node metastases compared with thecontrol. Although the weight gain was retarded in the TNP-470-treated mice,weight loss was not seen. TNP-470 was highly effective in the treatment ofbreast cancer cells. These results suggest that the clinical use of TNP-470may be a promising treatment for breast cancer patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005826129756
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  • 3
    Electronic Resource
    Electronic Resource
    Invasion-inhibiting factor 2-albumin conjugate inhibits invasion and spontaneous metastasis of MKL-4 human breast cancer cells transplanted into female nude mice (1996)
    Springer
    Clinical & experimental metastasis 14 (1996), S. 87-94 
    Details
    ISSN: 1573-7276
    Keywords: breast cancer ; invasion ; invasion-inhibiting factor 2 ; metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00121205
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  • 4
    Electronic Resource
    Electronic Resource
    Serum tumor marker kinetics and the clinical course of patients with advanced breast cancer (1996)
    Springer
    Surgery today 26 (1996), S. 250-257 
    Details
    ISSN: 1436-2813
    Keywords: breast cancer ; serum tumor marker ; carcinoembryonic antigen ; CA 15-3 ; tissue polypeptide antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00311583
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  • 5
    Electronic Resource
    Electronic Resource
    Timing of surgery in relation to the menstrual cycle and its influence on the survival of Japanese women with operable breast cancer (1995)
    Springer
    Surgery today 25 (1995), S. 519-524 
    Details
    ISSN: 1436-2813
    Keywords: breast cancer ; timing of surgery ; prognosis ; menstrual cycle ; estrogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been suggested that the timing of surgery during periods of unopposed estrogen circulation, when high blood levels of estrogen and low blood levels of progesterone exist, has a deleterious effect on the survival of premenopausal patients with breast cancer. We studied this controversial issue by examining the serum estradiol and progesterone levels of 38 premenopausal patients with primary breast cancer, and by analyzing data on 100 premenopausal patients treated for primary breast cancer. The survival of 31 patients who had undergone initial surgery between days 3 and 12 after their last menstrual period (group E) was compared with that of 69 patients who had undergone surgery between days 0 and 2 or from 13 days after their last menstrual period (group P). The overall survival of group E was significantly worse than that of group P (P=0.049). This difference was especially notable in patients with node-positive tumors or tumors larger than 2 cm in size; however there was no significant difference in disease-free survival between the two groups. On a multivariate analysis, nodal status was the only significant prognostic factor for both overall and disease-free survival. Thus, these findings suggest that unopposed estrogen circulation may be detrimental to the overall survival of premenopausal women with breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00311308
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  • 6
    Electronic Resource
    Electronic Resource
    The practice of breast self-examination results in the earlier detection and better clinical course of Japanese women with breast cancer (1994)
    Springer
    Surgery today 24 (1994), S. 337-341 
    Details
    ISSN: 1436-2813
    Keywords: breast self-examination ; questionnaire survey ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using a questionnaire survey, we analyzed the relationship between the frequency of breast self-examination (BSE) and the clinical stage and course of breast cancer in Japanese patients. BSE had been performed monthly by only 5.4% of the patients (M group), occasionally by 35.4% (O group), and not at all by 59.2% (N group). There was a positive relationship between more frequent BSE and an earlier clinical stage, the percentages of Tis/stage 0 and I for the M, O, and N groups being 83%, 44%, and 36%, respectively (P〈0.05). The mean maximum tumor diameters for the three groups were 1.7cm, 2.5cm, and 3.0cm, respectively. The tumor size in the M and O groups was significantly smaller than that in the N group atP〈0.01 andP〈0.05, respectively. The percentages of patients in the M, O, and N groups who underwent breast-conserving therapy were 42%, 11%, and 19%, respectively, with patients who had performed monthly, BSE more frequently undergoing breast-conserving therapy (P〈0.05). At a median follow-up time of 34 months, 0%, 3.8%, and 7.6% of the patients from the M, O, and N groups, respectively, had died of breast cancer, the overall survival curve of the M group being significantly better than that of the N group (P〈0.01). This retrospective study suggests the positive correlation of BSE frequency with earlier detection, and a more favorable clinical course in Japanese breast cancer patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02348564
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