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

Abstract

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.

In vitro thermo- and thermochemo-sensitivity of retinoblastoma cells from surgical specimens

“…The thermosensitivity of melanoma and colorectal cancer has been examined in vitro using the same HTCA technique under the same experimental conditions as this study, 428C for 1 h. Mann et al 11 reported that in melanoma, 25% of 53 cases were heat-sensitive by the criterion of T/C% µ 25%, and Murakami et al 12 reported that in colorectal cancer, 30% of 27 cases were sensitive (T/C% µ 30%). In the present study, 19.6% of 46 Rb tumours had a T/C% µ 30%, and 13.0% had a T/C% µ 25% (®gure 1).…”

“…To address this issue, Rb cells were obtained directly from fresh surgical specimens and their sensitivity to heat and various antitumour agents given at physiological or elevated temperatures was investigated in vitro. Similar studies performed on human tumours such as melanoma 11 and colorectal cancer 12 have successfully used the HTCA (human tumour clonogenic assay) established by Hamburger and Salmon 13 . This assay has been adapted to study the sensitivity of Rb cells to antitumour agents and preliminary results have been reporte d previously 14 .…”

Pseudomyxoma peritonei: A French multicentric study of 301 patients treated with cytoreductive surgery and intraperitoneal chemotherapy

“…A combination of cytoreductive surgery (CRS) with perioperative intraperitoneal chemotherapy (PIC) was proposed by Sugarbaker (8). The rationale behind this strategy was to resect visible disease and any occult residual disease would be treated with a high concentration of chemotherapy and hyperthermia which mutually potentiate one another's effects (9,10). Fifteen years and 600 publications later (7), a systematic review of this novel treatment concluded that this combined approach was very probably superior to conventional therapy, even in the absence of controlled M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 5 5 randomized trials, and even with evidence from only five series of more than 100 cases (11)(12)(13)(14)(15)(16).…”