Chemosensitivity correlation between the primary tumors and simultaneous metastatic lymph nodes of patients evaluated by DNA synthesis inhibition assay

Abstract

The chemosensitivities of primary tumors (PT) and simultaneous metastatic lymph nodes (MN) to mitomycin C (MMC), 5-fluorouracil (S-FU), Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), carboquone (CQ), or cisplatin (CDDP) were assessed in a group of 29 patients (11 gastric, 8 colorectal, 4 breast, and 6 other cancers) by a DNA synthesis (3H-thymidine incorporation) inhibition assay. PT and MN from the same patient showed heterogeneity in chemosensitivity. MN were more sensitive to the agents than PT. PT were sensitive to 5-FU, whereas MN were sensitive to CDDP. An analysis of the sensitivity correlations showed that the sensitivities of PT to MMC, 5-FU, CQ, and CDDP correlated with each other, but ADR sensitivity correlated with only CQ sensitivity. The sensitivities of MN correlated with each other, except for those to ADR and CDDP. In contrast, MMC, ADR, or CQ sensitivity showed a correlation between PT and MN. These results suggest that patients should be treated according to the sensitivity of the target lesion. However, if the sensitivity assay is not available, the sensitivity correlation may be useful when choosing the agent. It also may be important that ADR sensitivity does not correlate with the sensitivities of other agents. Cancer 65: [1273][1274][1275][1276][1277][1278]1990. N AN ATTEMPT to improve the response or survival rate I after cancer chemotherapy, a variety of anti-cancer chemosensitivity assays have been developed (e.g., colonyforming assay',2 and antimetabolic a~s a y~-~) .However, chemotherapy according to these sensitivity assays does not necessarily result in a remarkable improvement in the response or survival rate6 because these in vitro assays predict the resistance to the anti-cancer agent more accurately than the sensitivity to it.' Furthermore, the agreement rate between the in vivo response and the in vitro sensitivity is higher for metastatic lesions than primary There may be many reasons for these

Correlation between chemosensitivity and mRNA expression level of 5-fluorouracil-related metabolic enzymes during liver metastasis of colorectal cancer

“…In this model, however, up-regulation of DPD occurred during liver metastases. It became widely accepted that tumors were heterogeneous, and cells from individual tumors differed in biologic characteristics, cellular morphology, karyotype, growth rate, receptors, metabolism, and metastatic ability, even if tumors derived from one patient have the same origin or history (16). Studies have stated that some tumors arise from a small population of 'cancer stem cells,' which may be more resistant to chemotherapy and cause metastases (35,36).…”

“…The integrity of the rRNA bands was checked using agarose gel electrophoresis. Prepared total RNA (1 μg) was reverse-transcribed to synthesize cDNA using the oligo(dT) [12][13][14][15][16][17][18] primer and Superscript II (Invitrogen, Inc, Carlsbad, CA) according to the manufacturer's instructions. Expression levels of TS, DPD, TP, OPRT, and UP mRNA were measured by real-time quantitative RT-PCR (LightCycler; Roche Diagnostics GmbH, Mannheim, Germany) and LightCycler mRNA Quantification Plus kit for TS, DPD, and TP mRNA (Roche Diagnostics GmbH) according to the manufacturer's instructions.…”

“…Some reports indicate that the sensitivity to antitumor drugs, as determined by several sensitivity tests, differed between the primary tumors and their metastatic cancers (16)(17)(18). Several reports have shown that the expression levels of 5-FU-related metabolic enzymes differed from the sites of metastases (9,(19)(20)(21).…”

Nucleic acid synthesis in cancerous cells under the effect of gnidilatimonoein from Daphne mucronata

“…The [ 3 H]-uridine incorporation into RNA was achieved similar to the incorporation of [ 3 H]-thymidine into DNA except that 1 h before harvesting the cells, 1 ACi of [ 3 H]-uridine has been added to each well (Hall et al, 1982). The extent of inhibition of DNA and RNA synthesis were determined by the following equation: %inhibition = [1-test (cpm)]/[control (cpm)] Â 100 (Nio et al, 1990;Nio et al, 2000).…”

Anticancer chemosensitivity profile of freshly separated human pancreatic cancer cells assessed by DNA synthesis inhibition assay

“…The heterogeneity of chemosensitivity among the tumor cells derived from the same organ, or that between the primary and metastatic tumors in the same patient is thought to be one of the causes responsible for unsuccess-ful chemotherapy [22,23]. Clinical experience suggests that tumor cells from different lesions of the same patient show different chemosensitivity, and some reports have demonstrated this phenomenon in vitro [24,25], We have already demonstrated that metastatic tumors were more sensitive than primary tumors in patients with gastric or colorectal cancer by our results from a DNA synthesis inhibition assay [19]. The present study also showed that although only VP-16 was effective for primary pancreatic cancer, EPIR and CQ were effective for metastasis of pancreatic cancer as well and that metastasis of pancreatic cancer, except skin metastasis, was more sensitive than primary pancreatic cancer.…”