In vitro chemotherapy sensitivity testing of primary human colorectal carcinomas

Abstract

The cells obtained from 138 tumor samples taken from 135 patients with colorectal malignancies were cultured in vitro in a soft agar colony formation assay similar to that of Salmon and colleagues [1]. Significant colony formation occurred for 63 (51%) of evaluable tumor cultures, 53 of which were also tested against chemotherapeutic agents in vitro. The median number of drugs tested per tumor was 15. Using 70% inhibition of colony formation as the criterion for significant drug-induced cytotoxicity, only 3/53 (6%) of the tumors were noted to be sensitive to any drug. When colony counts generated by initially plated small tumor cell aggregates were taken into account, 8/40 (20%) of the tumors were noted to be sensitive in vitro to one or more agents. Because of the low rate of drug sensitivity found with this in vitro assay, its current role in the prospective assignment of chemotherapeutic treatment for patients with colorectal carcinoma is somewhat limited.

In vitro chemotherapy sensitivity patterns of human colon carcinoma continuous cell lines

“…It is our current opinion that the "true" pattern of in vitro sensitivity of the proliferative neoplastic "stem cells" from primary human tumors is somewhere in between the present results for cell lines and thosc previously reported by us for primary human colorectal carcinomas [3,4]. Attempts to modify soft agar colony formation assays for primary human colon tumors to eliminate various classes of technical artifacts that appear to yield "false-negative'' drug sensitivity patterns, including the use of universally cytotoxic "positive control" compounds such as sodium azide and the use of vital staining and incorporation of radioactive riucleic acid precursors, are underway.…”

“…Our data demonstrated that the probability of finding one or more highly cytotoxic drugs per tumor in vitro by this method was less than 20% [3,4]. These results were obtained despite the fact that colorectal tumor cells were exposed in vitro continuously to concentrations of drugs that we believe are representative of the maximum concentrations clinically achievable in patients' serum.…”

“…Cells from four wellcharacterized human colorectal carcinoma cell lines were exposed to anticancer drugs under conditions identical to those used for cells obtained from primary colorectal carcinomas [4]. Drug sensitivity patterns were measured using the same techniques.…”

Human Colon Cancer Tissues Are More Sensitive than Rectal Cancer Tissues to Antitumor Drugs in vitro

“…The colorectal cancer tissues were found to be less sensitive to various antitumor drugs, compared with other malignant tissues [4][5][6]. In cases of colon cancer, a combined chemotherapy has reduced hepatic metastasis and improved survival rates [7.…”

In vitro Sensitivity of Various Human Tumors to, l-Beta-D-Arabinofuranosylcytosine and, N⁴-Behenoyl-l-Beta-D-Arabinofuranosylcytosine

“…It is also used in com bined treatments of solid tumors [2]. The sensitivity to ara-C for treating human malignancy has been determined using various chemosensitivity tests [3,4], N4-behenoyl -1 -p -D -arabinofuranosylcytosine (BH-AC) is a synthetic lipophilic masked compound of ara-C [5,6], BH-AC is gradually dissociated into cytosine and the behenoyl chain, and is only affected by the cytidine deaminase: ara-C-inactivating enzyme [7], BH-AC is retained in the or gans longer than is ara-C [8], and shows high and prolonged antitumor activity, in experimental tumor systems [5]. The clini cal effect of BH-AC has been noted for treating acute leukemia and various solid tumors [9][10][11][12]; however, as little is known of BH-AC, we evaluated the antitumor ac tivity of BH-AC in different human tu mors, as compared to ara-C.…”