Thermal enhancement of oxaliplatin-induced inhibition of cell proliferation and cell cycle progression in human carcinoma cell lines.

Hyperthermia is used to treat intraperitoneal colorectal carcinomatosis. In this setting, the molecular effects of oxaliplatin and hyperthermia, in combination and alone, were deciphered in ovarian and colon cancer cells. The combined antiproliferative effects of hyperthermia and oxaliplatin (Eloxatine) on human IGROV-1 ovarian carcinoma, Caco-2 and HT-29 colon carcinoma cell lines were investigated by cell viability test, cell cycle analysis and modulation of expression of cell cycle-related proteins. Oxaliplatin inhibited growth of all cell lines in a dose-dependent manner. The efficacy of the drug was markedly enhanced by concurrent exposure to mild heat shock (1 h, 42 degree C). In IGROV-1 cells, a low concentration (15 microg/ml) of oxaliplatin in combination with hyperthermia induced a transient G2/M arrest. In both colon carcinoma cell lines, a G1/S arrest with a reduction of the G0/G1 population occurred. In IGROV-1 and Caco-2 cells, growth arrest was accompanied by apoptosis as suggested by the appearance of sub-G1 population. Time-course changes of cell cycle regulatory proteins levels revealed accumulation of cyclins A and B as well as of cdc2 and cdk2 upon exposure of IGROV-1 cells to hyperthermia and oxaliplatin. In this cell line, p53 appeared to be implicated in both G2/M arrest and apoptosis. G1/S arrest of HT-29 cells was linked to up-regulation of cyclin E and p27(Kip1) and accumulation of the hypophosphorylated form of pRB, whereas in Caco-2 cells only the hyperphosphorylated form was detected as well as a down-regulation of the proto-oncogene c-myc. Taken together, the results of these in vitro studies suggest that hyperthermia and oxaliplatin might elicit antiproliferative effects by modulating the expression of cell cycle regulatory proteins through different signalling pathways.

The distribution of nuclear progesterone receptor in the hypothalamus and forebrain of the domestic hen.

Cell nuclei containing progesterone receptor were identified immunohistochemically in the hypothalamus and forebrain of the domestic hen using an antiserum to the steroid binding "B" subunit (110 kDa) of chicken oviduct progesterone receptor and the avidin-biotin complex procedure. Cell nuclei containing progesterone receptor were widely distributed in the anterior, medial and basal hypothalamus with the highest density occurring in the lamina terminalis and the preoptic area. Abundant, though less intensely reacting progesterone receptor was present in cell nuclei in the tuberal infundibular area and in the internal zone of the median eminence. A large group of cell nuclei containing progesterone receptor occurred in the dorsal anterior hypothalamus between the anterior commissure and the lateral ventricle. This group of nuclei extended anteriorly into the telencephalon. A small number of cell nuclei containing progesterone receptor was also found in the ventral telencephalon in the region of the nucleus accumbens.