Biomedical subjects

R Higashikubo

Publications and source records attributed to R Higashikubo.

39 records · Page 3Linked to original sources

PubMedDate not supplied

Thermal radiosensitization of human tumour cell lines with different sensitivities to 41.1 degrees C.

While much work on radiosensitization by hyperthermia in the 43 degrees C and higher temperature range has been done, relatively little work has been done at temperatures in the 41-42 degrees C range. In this moderate hyperthermia range there are dramatic differences in the resistance of mammalian cells to hyperthermia. Therefore, thermal radiosensitization was measured in two human colon adenocarcinoma cell lines, one that expresses chronic thermotolerance and proliferates at 41.1 degrees C, NSY 42129 (NSY) cells and one that is slowly killed at 41.1 degrees C, HCT15 cells. Heat-resistant NSY cells were found to be more radioresistant than heat-sensitive HCT15 cells. Hyperthermia at 41.1 degrees C enhanced the radiation sensitivity in NSY cells, but no significant induction of heat-induced radiosensitization was observed in HCT15 cells. The radiation sensitivity induced by 41.1 degrees C in NSY cells appeared to be related to both intrinsic heat-induced radiosensitization (HIR) and cell-cycle redistribution at 41.1 degrees C. Incidentally, cells incubated at 41.1 degrees C for between 8-16 h displayed an identical radiosensitivity to those heated for 24 h. This result implies that modest hyperthermia for 2 h or more can have a radiosensitizing effect in heat-resistant cells.

Adenocarcinoma↗

PubMedDate not supplied

Chronic thermotolerance with continued cell proliferation.

The human colon adenocarcinoma cell line, NSY42129, is capable of proliferation at 41.1 degrees C. This ability appears to be due to a type of chronic thermotolerance, as opposed to selection or adaptation, that allows these cells to traverse S phase at elevated temperatures. Four other human cell lines were studied for their ability to proliferate at 41.1 degrees C. Of those only one, also a colon adenocarcinoma, showed the ability to sustain proliferation at 41.1 degrees C. While all the cell lines examined showed increased levels of the major heat shock proteins at 41.1 degrees C, the cellular amounts of these proteins did not correlate with their ability to proliferate at 41.1 degrees C. However, the ability of the cells to proliferate at 41.1 degrees C did correlate with their ability to sustain elevated rates of synthesis of hsp70 and hsp90. These results could have implications in the clinical application of hyperthermia, particularly the use of long duration moderate hyperthermia.

Bromodeoxyuridine↗

PubMedDate not supplied

Intracellular distribution of hsp70 during long duration moderate hyperthermia.

Hyperthermia causes cell killing and is also an effective radiosensitizer. In recent years, the protocol of long duration moderate hyperthermia (LDMH) has been used to treat cancer patients in the clinic. However, the results of many studies indicate that some tumour cells may reveal the capability to express chronic thermotolerance, a factor of potentially critical impact in the efficacy of clinical hyperthermia. Previously it has been reported that two out of five human cell lines studied were able to proliferate at 41.1 degrees C. In the present study, the intracellular distribution of hsp70 during LDMH was measured as a potential marker for chronic thermotolerance with continued cell proliferation. In all cell lines studied, hsp70 became localized in the nucleus immediately after the cells were shifted from 37 degrees C to 41.1 degrees C. However, in the two cell lines which recovered and continued to proliferate, NSY42129 and HT29, hsp70 was delocalized from the nucleus within 4 h. Conversely, in the cell lines for which 41.1 degrees C was lethal, hsp70 did not delocalize from the nucleus but rather became localized in the nucleolar regions. Neither the NSY42129 cells nor the HT29 cells showed any preferential nucleolar punctate staining. Thus, it appears that the pattern of hsp70 nuclear localization and delocalization is related to the cells' ability to survive moderate heat shocks.

Cell Division↗