Review: Biologic heterogeneity of cancer metastases

Fidler, Isaiah J.

doi:10.1007/bf01806690

Cited by 56 publications

(23 citation statements)

References 63 publications

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“…This indicates that these drugs are highly active in vitro. Reported clinical response rates for these drugs compared to 5-FU, ADR and cyclophospha mide support these findings [18,22,27,28], In general tumor response to chemotherapeutic agents is character ized by its heterogeneity [1]. All cell lines responded in a different dose-related manner.…”

Section: Discussionsupporting

confidence: 64%

“…However, patients with the same tumor pathology may not respond to the same drug treatment. Tumor heterogeneity is well known in breast cancer [1], Drugs can then be tested in several assays to obtain chemosensitivity profiles [2], The ATP cell viabili ty assay (ATP-CVA) is a relatively new system to assess chemosensitivity by measuring total cell kill [3][4][5][6][7], This test has been adopted for chemosensitivity testing of human gynecologic malignancies, with promising prelim inary results with regard to clinical correlation between in vitro sensitivity and in vivo results. Further, the results of ATP-CVA compare very well with those of other chemo sensitivity assays, especially the clonogenic assay and thy midine uptake methods [3-5, 7, 8], In contrast, the ATP-CVA does not rely only on assessment of S-phase cells (thymidine uptake) or the ability of tumor cells to prolifer ate (clonogenic assay) but on total cell kill.…”

Section: Introductionmentioning

confidence: 99%

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Comparative Chemosensitivity Profiles in Three Human Breast Cancer Cell Lines with the ATP-Cell Viability Assay

Koechli

Sevin²,

Perras³

et al. 1994

Oncology

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In this study the dose-response curves for doxorubicin, pirarubicin, 5-fluoro-uracil, 4-hydroperoxy-cyclophosphamide and taxol were obtained in three breast cancer cell lines (MCF-7, T47D and BT-20). The ATP cell viability assay was chosen to evaluate the chemosensitivity profiles and was a reproducible, practicable method to assess drug response in breast cancer cell lines. The IC50 values were calculated on the median effect principle and indicated that taxol was the most active drug tested in this study with a mean IC50 value of 0.02 μM. This in vitro effect correlated well with clinical observations in metastatic breast cancer where taxol proved to be a very active drug. Pirarubicin was the second most active drug tested with an IC50 value 10 times less compared to that of doxorubicin. The results obtained with the ATP cell viability assay are promising, therefore further testing with drug combination chemotherapy and fresh human breast cancer tumor testing are warranted and ongoing.

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Comparative Chemosensitivity Profiles in Three Human Breast Cancer Cell Lines with the ATP-Cell Viability Assay

Koechli

Sevin²,

Perras³

et al. 1994

Oncology

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“…(13) Therefore, we stress the importance of identifying organ-specific characteristics of metastatic breast cancer, because such data can further the understanding of the natural history of the disease. (5,14) The objective of this study was to identify the clinical and pathological factors that affect the survival of patients with a history of breast 489 pleural effusion, the mean age at death was 57.8 ± 12.0 years. Therefore, the mean time from the diagnosis of the primary tumor to the identification of malignant pleural effusion was 20 months, and the mean survival after the identification of malignant pleural effusion was 6 months.…”

Section: Introductionmentioning

confidence: 99%

Fatores clínicos e anatomopatológicos que influenciam a sobrevida de pacientes com câncer de mama e derrame pleural neoplásico

et al. 2012

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Objective: The objective of this study was to identify the clinical and pathological factors that can influence the prognosis of breast cancer patients with clinical symptoms of malignant pleural effusion. Methods: This was a clinical cohort study, in which we analyzed the medical charts of patients diagnosed with malignant pleural effusion between 2006 and 2010. By examining the charts, we identified the female patients with a history of breast cancer. For those patients, we collected pathology data related to the primary tumor and cytopathology data related to the pleural metastasis. Results: We evaluated 145 patients, 87 (60%) of whom had tested positive for malignant cells in the pleural fluid. Ductal histology was observed in 119 (82%). The triple-negative breast cancer phenotype was seen in 25 cases (17%). Those patients had the worst prognosis (with a sharp decline in the survival curve), and 20 of the 25 (80%) died during the follow-up period (through June of 2011). The mean survival after the identification of malignant pleural effusion was 6 months. Conclusions: In patients with triple-negative breast cancer who test positive for malignant cells in the pleural fluid, the prognosis is poor and survival is reduced.Keywords: Pleural effusion, malignant/mortality; Breast neoplasms/mortality; Breast neoplasms/genetics. ResumoObjetivo: O objetivo deste estudo foi identificar os fatores clínicos e anatomopatológicos que possam influenciar o prognóstico de pacientes com câncer de mama e sintomas clínicos de derrame pleural neoplásico. Métodos: Trata-se de um estudo clínico de coorte, no qual foram analisados os prontuários médicos de pacientes que receberam diagnóstico de derrame pleural neoplásico entre 2006 e 2010. Por meio da análise dos prontuários, identificamos as pacientes com história de câncer de mama. Para essas pacientes, coletamos dados anatomopatológicos relacionados ao tumor primário e dados citopatológicos relacionados à metástase pleural. Resultados: Das 145 pacientes avaliadas, 87 (60%) apresentaram, no exame citológico, resultado positivo para células neoplásicas no líquido pleural; além disso, 119 (82%) apresentaram tipo histológico ductal. O fenótipo triplo-negativo foi observado em 25 pacientes (17%), as quais apresentaram o pior prognóstico, com queda acentuada na curva de sobrevida. Das 25 pacientes, 20 (80%) evoluíram a óbito durante o período de seguimento (até junho de 2011). A sobrevida média após a identificação de derrame pleural neoplásico foi de 6 meses. Conclusões: Em pacientes com câncer de mama triplo-negativo e exame citológico com resultado positivo para células neoplásicas no líquido pleural, o prognóstico é ruim e a sobrevida é menor. cancer who develop pleural effusion. To that end, we evaluated factors related to the diagnosis, the histological type of the primary tumor, the identification of malignant cells in the pleural fluid, the expression of immunohistochemical markers of breast cancer, and outcomes. MethodsThis was a hospital-based, historical cohort study...

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“…Meanwhile, experimental and some clinical data suggest that 1) the primary tumor is genetically heterogeneous, 2) the clones responsible for organ dissemination may not even be present in the primary tumor but develop through sequential genetic alterations, and 3) they compose a very small percentage of the primary tumor. 11 Earlier studies exclusively used HercepTest to assess the maintenance of HER-2/neu genotype in metastatic lesions and found it concordant in case of lymph node, liver and lung metastases. [12][13][14][15][16] Recent reports provided evidence that the HER-2/neu genotype of BRC may change in the metastases: loss of HER-2/neu expression was reported in one case in pleural metastases, 17 while loss of HER-2/neu amplification was found in 21%, but appearance of HER-2/neu amplification was even more frequent in visceral metastases (30%).…”

Section: Introductionmentioning

confidence: 99%