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PubMedDate not supplied

Different roles for K+ channels in cisplatin-resistant cell lines argue against a critical role for these channels in cisplatin resistance.

Cisplatin resistance has been associated with altered K+ fluxes. Here, we focused our investigations on the detection of K+ channels in a series of cisplatin-resistant (CP-r) cells with increasing resistance and on the functional relationship of these K+ channels to resistance. Microarray analysis and confocal microscopy indicated that there was overexpression of the ether-a-gogo gene (HERG) and the inwardly rectifying potassium channel gene (TWIK) in a human epidermal KB and human liver BEL-7404 carcinoma cell line series selected for cisplatin resistance. With increased resistance, the plasma membrane potential, but not the mitochondrial membrane potential, also increases in these two series. For these reasons, we conducted cell proliferation studies in the presence of either antibodies directed against the detected K+ channels, omeprazole (a H+ pump inhibitor) or a specific inhibitor of the HERG channel (WAY-123398-A-5). The antibodies and omeprazole influenced cell growth only very slightly. The specific K+ channel blocker did not alter cisplatin resistance. We also observed that manipulation of K+ fluxes with antibodies and the H+ pump with omeprazole resulted in opposite effects on cisplatin resistance in these two cell lines. We conclude that K+ and H+ homeostasis are not critical factors in cisplatin resistance since they affect cisplatin resistance differently in KB and BEL-7404 cells.

Antineoplastic Agents↗
PubMed2006

[The role of the preoperative radiochemotherapy and the role of neoadjuvant chemotherapy before radical Wertheim-Meigs hysterectomy for cervical cancer stage I B - II B].

One of the most important prognostic factors for early stages cervical cancers is the tumour size. The patients with size of the tumour bigger than 4 sm in diameter have worse prognosis. The aim of our research work was to compare the efficacy of preoperative radiochemotherapy and neoadjuvant intravenous chemotherapy, followed by radical hysterectomy a modo Wertheim-Meigs for stage I B - II B cervical cancer. We summerized our and foreign experience in this field. From 1998 till 2005 we examined 123 patients in stage I B - II B cervical cancer treated by preoperative percutaneous radiotherapy (dosis 45 Gy) plus cisplatin (50 mg/m2) compared with preoperative chemotherapy cisplatin (50 mg/m2), vincristin 1 mg/m2 every 7-10 days for 3 courses. Radical hysterectomy a modo Wertheim-Meigs was performed 4-5 weeks after the preoperative treatment. There is no significant difference in the age groups, stages of the tumour, the tumour size end the histopathological kind of the tumour between the 2 groups of examined patients. The toxicity in the two groups was mild. In the group with preoperative radiochemotherapy 4 patients developed vesicovaginal fistulas, 3 patients hydronephrosis. After the surgical treatment the invasion of the tumour in the parametrial region and the lymph nodes was without any significant difference between the two groups (p>0.06). In the group with neoadjuvant chemotherapy more patients had a residual tumour, but about the size of the tumours in the two groups there was no significant difference (p>0.05). The final pathological response was higher in the group received radiochemotherapy. Acording to the results of our research work the neoadjuvant chemotherapy and the radiochemotherapy have nearly equal effect on the prognostic factors connected with survival.

Chemotherapy, Adjuvant↗
PubMedDate not supplied

[Age-related characteristics of the role of the endothelium in the response of vascular smooth muscles to hormones. The role of ultrastructural changes].

The experiments performed on isolated preparations of femoral artery and aorta of the mature and old rats as well as on those of coronary arteries of adult and old subjects failed to reveal direct participation of endothelium in the realization of insulin and vasopressin effects on the smooth muscles of the vessels studied. However, the endothelium modulated their influence on the vessels in the mature age. The lack of modulating effect of the endothelium in old age may be a result of its structural changes and thickening of a hemato-cellular barrier of the vessel wall observed by electron microscopy.

Adult↗