RESUMO
Cisplatin is a widely used platinum-based anticancer drug in the chemotherapy of numerous human cancers. However, cancer cells acquire resistance to cisplatin. So far, functional loss of volume-sensitive outwardly rectifying (VSOR) Cl- channels has been reported to contribute to cisplatin resistance of cancer cells. Here, we analyzed protein expression patterns of human epidermoid carcinoma KB cells and its cisplatin-resistant KCP-4 cells. Intriguingly, KB cells exhibited higher ß-actin expression and clearer actin filaments than KCP-4 cells. The ß-actin knockdown in KB cells decreased VSOR Cl- currents and inhibited the regulatory volume decrease (RVD) process after cell swelling. Consistently, KB cells treated with cytochalasin D, which depolymerizes actin filaments, showed smaller VSOR Cl- currents and slower RVD. Cytochalasin D also inhibited cisplatin-triggered apoptosis in KB cells. These results suggest that the disruption of actin filaments cause the dysfunction of VSOR Cl- channels, which elicits resistance to cisplatin in human epidermoid carcinoma cells.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Canais de Cloreto/genética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Citoesqueleto de Actina/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , HumanosRESUMO
On mixing (Rf SO2 )2 CH2 (Rf =perfluoroalkyl), paraformaldehyde, and substituted pyridines, a three-component reaction proceeded smoothly to give unusual zwitterions bearing both pyridinium and stabilized carbanion moieties in good to excellent yields. Of these, 2-fluoropyridinium derivatives rapidly dissociated in acetonitrile to give equilibrium mixtures of the zwitterions and (Rf SO2 )2 C=CH2 /2-fluoropyridine, as confirmed by detailed variable-temperature NMR studies. The dynamic behavior of such 2-fluoropyridinium compounds allows them to be used as shelf-stable, easy-to-handle sources of (Rf SO2 )2 C=CH2 . With these reagents, strongly acidic carbon acids (Rf SO2 )2 CHR were synthesized, which served as a new type of acid catalysts. Moreover, C-C bond-forming reactions with a ketene silyl acetal proceeded efficiently with Tf2 C=CH2 generated in situ.
RESUMO
Campylobacter was isolated from retail meat samples collected during the fiscal year 2009 in Japan. The higher percentages of contamination of chicken products were observed from June (39.3%) to November (83.3%). However, the highest number of human campylobacteriosis cases was reported in June in the Infectious Agents Surveillance Report. The chicken isolates with distinct clusters IVb and I, based on the restriction fragment length polymorphism of the flaA gene, were predominantly obtained during the periods between April and November 2009 and between February and March 2010, respectively. Extensive monitoring of Campylobacter contamination in chickens produced in various places is needed to analyse the seasonal variations between contamination of the meat products and the number of human cases with campylobacteriosis.