Heterogeneity of Human Metastatic Clones by In Vitro Chemosensitivity Testing

Korn, Edward I.; Morton, Donald L.

doi:10.1001/archsurg.1983.01390120036010

Cited by 8 publications

(2 citation statements)

References 17 publications

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“…The tumor cells examined in this paper, however, were all obtained from primary lesions of human cancer. There are some studies [5,22,25] reporting the differences in sensitivity to drugs that result from heterogeneity between the primary and metastatic lesions. The heterogeneity of cells in pri mary and metastatic lesions needs further investiga tion in analysis of thermochemosensitivity of tumors.…”

Section: Discussionmentioning

confidence: 99%

“…6, 9, 16] and in vivo [18,21], Cancer thermochemotherapy has been introduced as a clinical modality [13,15] with limited success. However, heterogeneity between patients of the sensitivity of tumor cells to various drugs has been well documented [5,22] and suggests that populations of cells have individual differences in sensitivity to heat and to heat plus anticancer agents. It is advan tageous to be able to predict the thermosensitivity of a patient's tumor before the application of ther motherapy, and such predictions may, in the future, allow some individualization of thermochemotherapy in terms of selection of specific agents.…”

Section: Introductionmentioning

confidence: 99%

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Thermochemosensitivity: Augmentation by Hyperthermia of Cytotoxicity of Anticancer Drugs against Human Colorectal Cancers, Measured by the Human Tumor Clonogenic Assay

Murakami

Koga²,

Maeta³

1988

Oncology

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Thermochemosensitivity was examined in vitro by a human tumor clonogenic assay (HTCA) using specimens obtained surgically from 43 patients with colorectal cancer. We found that the percentages of patients whose cells showed higher sensitivity (greater than 70% inhibition of colony formation) to hyperthermia alone were 29.6 and 55.6% at 42 and 43 °C each for 1 h, respectively. Similarly, percentages of patients whose cells were sensitive to drugs alone were 13.8, 24.1 and 48.3%, for cis-diamminedichloroplatinum(II), 5-fluorouracil and mitomycin C, respectively. These sensitivities were augmented when hyperthermia was combined with administration of anticancer agents. Even in tumor cells that were insensitive to anticancer drugs alone or to hyperthermia alone, sensitivity was enhanced when administration of drugs was combined with hyperthermia. Our results demonstrate that HTCA of tumor cells, obtained from suitable patients, may be useful as a predictive test for application of thermotherapy and for individualization of chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thermochemosensitivity: Augmentation by Hyperthermia of Cytotoxicity of Anticancer Drugs against Human Colorectal Cancers, Measured by the Human Tumor Clonogenic Assay

Murakami

Koga²,

Maeta³

1988

Oncology

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Adriamycin-induced resistance to natural killer (NK)-mediated cytotoxicity

Wood

Lotzová

1989

Cancer

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Studies were done to determine the susceptibility of a colon carcinoma cell line, LoVo, to natural killer (NK) mediated lysis after exposure of the tumor cells to Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH). LoVo cells were exposed to ADR (0.4 pg/ml) for various time intervals and then tested for sensitivity to lysis by NK cells from the peripheral blood of normal donors in a sodium chromate (Cfi') release cytotoxicity assay. Exposure of tumor targets to ADR induced a resistance to NK-mediated lysis. Susceptibility to lysis decreased progressively to approximately 60% of control levels after 72 hours of ADR exposure. The induction of resistance was dependent on ADR dose, but did not magnify with doses greater than 0.4 pg/ml. When target cells were allowed to recover from ADR in fresh medium for 48 hours, complete reversal of the ADR effect was seen. The effect of interleukin-2 (IG2) stimulation on the NK lysis of LoVo also was tested. IG2-stimulated effector cells demonstrated enhanced cytotoxicity to LoVo targets and were able to overcome the ADR-induced resistance to lysis. The mechanism of resistance does not appear to be related to the altered binding of effectors to chemotherapy-treated targets, as suggested by single cell assay results.Cancer 64396-403, 1989. DISTINCT SUBPOPULATION of lymphoid Cells, theA natural killer (NK) cells, possesses spontaneous reactivity against a variety of tumor cell lines, including primary tumor cells and virus-infected cell lines, and may be important in anti-cancer defense.' The effect of chemotherapy on the sensitivity of target cells to lysis by effector immune cells has not been well defined. A previous study has shown that K-562 targets acquire resistance to NK cells afler ADR treatment.2 The results of our research demonstrate a similar phenomenon, using a different tumor cell line. In addition, we have tested whether or not such decreased sensitivity to lysis can be overcome by interleukin-2 (IL-2) stimulated NK cells. Our results showed that IL-2-activated effectors were able to kill the Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH) treated colon carcinoma cells. Also, the resistance to NK-mediated lysis was reversed by allowing the target cells to recover from the ADR treatment.

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Prognostic factors and in vitro cytotoxic sensitivity in colorectal cancer

Trotter

Morgan

Goeting

et al. 1984

British Journal of Surgery

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The poor response rates to chemotherapy for colorectal cancer justify attempts to rationalize selection of patients for treatment, and the development of systems to evaluate new cytotoxic agents. Refinement of prognostic indices may identify colorectal cancer patients at a higher risk of recurrence who merit more aggressive treatment. We report our experience with the stem cell assay and pulse thymidine labelling in 43 primary colorectal cancers. Thirty-six tumours were evaluable, and clonogenic growth was obtained in 30 (83 per cent). In 24 tumours (67 per cent) growth was adequate for meaningful interpretation of a cytotoxic drug assay. Frequency of growth and colony forming efficiency did not correlate with histopathological grade, Dukes' stage or tumour cell kinetic indices. Thymidine labelling indices correlated with Dukes' stage (A and B versus C and D, P less than 0.01, Mann-Whitney U test). Cytotoxic assays with 5-fluorouracil and 5'-deoxy-5-fluorouridine were undertaken in 18 cases (14 primary carcinomas, 4 malignant ascites), of which 14 were evaluable and 3/14 (21.5 per cent) were chemosensitive in vitro. Both drugs were equally effective in vitro at clinically attainable plasma concentrations. This is in accordance with the response rates observed clinically with 5-FU chemotherapy in colorectal cancer.

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Heterogeneity of Human Metastatic Clones by In Vitro Chemosensitivity Testing

Cited by 8 publications

References 17 publications

Thermochemosensitivity: Augmentation by Hyperthermia of Cytotoxicity of Anticancer Drugs against Human Colorectal Cancers, Measured by the Human Tumor Clonogenic Assay

Thermochemosensitivity: Augmentation by Hyperthermia of Cytotoxicity of Anticancer Drugs against Human Colorectal Cancers, Measured by the Human Tumor Clonogenic Assay

Adriamycin-induced resistance to natural killer (NK)-mediated cytotoxicity

Prognostic factors and in vitro cytotoxic sensitivity in colorectal cancer

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