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  • 1
    ISSN: 1573-7217
    Keywords: breast cancer cell culture ; chemosensitivity assay ; in vitro ; drug response ; doxorubicin ; epidoxorubicin ; vinblastine ; cis platinum ; idarubicinol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The feasibility of techniques developed for isolating and culturing human mammary epithelial cells of malignant origin was confirmed in 136 primary breast cancers, 116 hypodermal metastases, and 8 metastatic lymph nodes. In 115 (84%) primary breast cancers and in 81 (70%) hypodermal recurrences we observed a goodin vitro cellular proliferation. These proliferating cells, at the second passage, were used for a clonal assay suitable for quantitating drug sensitivity. With this clonal assay median cloning efficiencies of 14% and 6% were obtained respectively in primaries and in skin recurrences. We examined thein vitro response to different drugs and confirmed the test's ability to detect heterogeneity in response to same drugs (doxorubicin, 4′-epidoxorubicin, vinblastine, cis platinum, and idarubicinol) among the different breast carcinoma cultures as well as heterogeneity among subpopulations within a single carcinoma.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7217
    Keywords: biologic markers ; node-negative breast cancer ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is generally thought that future advances in the treatment and cure of breast cancer patients will be made possible through a deeper understanding of tumor biology and an improved capability to define the prognosis of each single patient. This will lead to the formulation of new, more selective, and patient-tailored therapies. It is therefore important, when studying potential prognostic factors, to follow methodologic requirements and guidelines which involve the carrying out of prospective studies as confirmatory steps. Repeatedly or recently investigated prognostic markers (tumor size, menopausal status, ER, PgR, 3H thymidine labeling index, c-erbB-2 and p27 expression) were evaluated on a series of 286 prospectively recruited node negative breast cancer patients who underwent loco-regional treatment alone and were closely followed. The individual and relative prognostic contribution of each variable with respect to other factors, as well as their ability to identify node negative patients at risk, were assessed by univariate and multivariate analysis. At a five-year follow-up, only tumor size (p = 0.021) and TLI (p = 0.016) individually proved to be significant prognostic indicators of relapse-free survival. Conversely, p27 expression was not related to RFS and c-erbB-2 expression appeared to have only a short-term effect on patient prognosis. TLI and tumor size, tested in multivariate analysis along with ER and menopausal status, maintained their independent prognostic relevance. The study, performed on a large series of node-negative patients given loco-regional treatment alone, for the first time prospectively recruited, showed the prognostic relevance of TLI and its independence from other clinico-pathologic and biologic factors over a five-year period.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7217
    Keywords: adriamycin ; breast cancer ; chemosensitivity assay ; lonidamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Lonidamine is a new potential chemotherapeutic agent, relatively non-toxic, that can positively modulate the efficacy of several antineoplastic drugs. We evaluated the response of two established human breast cancer cell lines (MCF-7 and BRC-230) and of 20 primary breast cancer cell lines to lonidamine, either alone or in combination with adriamycin, the drug most widely used in the management of breast cancer. Different schedules were tested by varying either concentration of the drugs (LND: 10–150µg/ml; ADM: 0.10–0.15µg/ml), or time of exposure (1–96 hours), or sequence of administration (ADM → LND; LND → ADM; ADM + LND). Our results indicate slight sensitivity of the cell lines to lonidamine when used alone, whereas an increase of efficacy was noted when lonidamine was added for at least 24 hours after a 4 hour exposure to adriamycin. Such efficacy was significantly greater than that expected from an additive effect between the two drugs. We conclude that lonidamine, when given according to an appropriate schedule, enhances,in vitro, the efficacy of adriamycin. A correct employment of lonidamine in the management of breast cancer might therefore potentiate the therapeutic effect of adriamycin.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7217
    Keywords: cell proliferation ; chemotherapy ; metastatic breast cancer ; predictive value
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Many biologic prognostic markers are available for patientswith breast cancer, and considerable interest has beendevoted to confirm preliminary evidence of their roleas indicators of treatment response. It remains tobe assessed whether such markers are predictors ofresponse only to first-line or also to successivetherapies. Proliferative activity, defined by the3H-thymidine labelingindex (TLI), was determined on the primary lesionfrom 76 patients at time of first diagnosis.At relapse, patients underwent chemotherapy as absolute (48cases) or relative (28 cases) first-line treatment, andtheir clinical response was analyzed in relation tothe TLI of the primary lesion. The objectiveclinical response was significantly higher for rapidly (47%;CL, 33–61%) than for slowly proliferating tumors (15%;CL, 1–29%). These findings held true also whenadjusted for metastatic site, previous treatment, chemotherapy regimenadministered, and hormone receptor status. However, the directrelation between cell proliferation and benefit from chemotherapyheld true only when such a treatment wasused as an absolute first-line approach. Cell proliferationof primary lesions represents a consistent indicator ofresponse to chemotherapy over time. Previously administered regimens,at least hormone therapy, could alter the proliferation-relatedchemosensitivity profile of individual tumors.
    Type of Medium: Electronic Resource
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