Restoration of paclitaxel resistance by CDK1 intervention in drug-resistant ovarian cancer.

Epithelial ovarian cancer (EOC) commonly acquires resistance to chemotherapy, and this is the major obstacle to the better prognosis. Elucidating the molecular targets altered by chemotherapy is critically required to understand and overcome drug resistance. As a drug combination including paclitaxel is a prevalent prescription for treatment of EOC, to uncover gene expression altered in paclitaxel-resistant EOC, we analyzed multidirectional microarray profiles in both EOC cell lines and patients with paclitaxel resistance.

Transcriptome analysis indicates TFEB1 and YEATS4 as regulatory transcription factors for drug resistance of ovarian cancer.

Ovarian cancer is an intractable disease because patients with ovarian cancer frequently develop drug resistance after long-term chemotherapy. Despite the availability of cumulative information on drug-resistant patients, strategies to reverse drug resistance have still not been established. In this study, we analyzed drug resistance-associated transcription factors (TFs) in ovarian cancer.

Differential inhibitory effects of two Raf-targeting drugs, sorafenib and PLX4720, on the growth of multidrug-resistant cells.

B-Raf is the most frequently mutated protein kinase in the MAPK signaling cascade in human cancers, making it an important therapeutic target. Here, we describe the differential effects of two Raf-targeting drugs, sorafenib and PLX4720, on multidrug-resistant v-Ha-ras-transformed cells (Ras-NIH 3T3/Mdr). We demonstrate that the growth of the NIH 3T3/Mdr cell line was affected in a dose-dependent manner more significantly by the pan-Raf inhibitor sorafenib than by the selective mutant B-Raf inhibitor PLX4720.

Targeting the autophagy pathway using ectopic expression of Beclin 1 in combination with rapamycin in drug-resistant v-Ha-ras-transformed NIH 3T3 cells.

The effectiveness of an apoptosis-targeting therapy may be limited in tumor cells with defects in apoptosis. Recently, considerable attention in the field of cancer therapy has been focused on the mammalian rapamycin target (mTOR), inhibition of which results in autophagic cell death. In our study using multidrug-resistant v-Ha-ras-transformed NIH3T3 (Ras-NIH 3T3/Mdr) cells, we demonstrated that rapamycin-induced cell death may result from 2 different mechanisms.

Crosstalk between autophagy and apoptosis in the regulation of paclitaxel-induced cell death in v-Ha-ras-transformed fibroblasts.

The previous studies by this author group has shown that paclitaxel, a mitotic inhibitor used in breast cancer chemotherapy, inhibits cell growth via induction of Raf-1-dependent apoptosis. In this article, the role of autophagy in paclitaxel anticancer action was investigated using v-Ha-ras-transformed NIH 3T3 cells. Paclitaxel induced a notable increase in the number of fluorescent particles labeled with monodansylcadaverine (MDC), a specific marker for autophagic vacuoles.

Spry2 does not directly modulate Raf-1 kinase activity in v-Ha-ras-transformed NIH 3T3 fibroblasts.

Sprouty (Spry) proteins have previously been suggested as negative regulators of the MAPK pathway through interaction with Raf-1. However, the molecular basis of this inhibition has not been elucidated. In this study, we used cells expressing FLAGtagged Raf-1 with point mutations at known phosphorylation sites to reveal that activation of Raf-1 mutants does not correlate with their degree of interaction with Spry2.

Assessment of the dermal and ocular irritation potential of lomefloxacin by using in vitro methods.

The evaluation of eye and skin irritation potential is essential to ensuring the safety of human in contact with a wide variety of substances. Despite this importance of irritation test, little is known with respect to the irritation potency of lomefloxacin, a fluoroquinolone antibiotic, which has been known to cause phototoxicity with an abnormal reaction of the skin. Thus, to investigate the tendency of lomefloxacin to cause eye and skin irritation, we carried out in vitro eye irritation test using Balb/c 3T3, and in vitro skin irritation test using KeraSkin(TM) human skin model system.

The difference in biological properties between parental and v-Ha-ras transformed NIH3T3 cells.

Purpose: We performed experiments to investigate the change in cellular signaling that occurs during the transformation of a normal cell to a cell capable of cancerous growth, and we did so by using the NIH 3T3 cells that were transformed by transfection with the v-Ha-ras oncogene.

Materials And Methods: Parental and v-Ha-ras transfected NIH 3T3 cells were chosen as test systems. The siRNA transfections were performed using Lipofectamine 2000.

The enhancement of Raf-1 kinase activity by knockdown of Spry2 is associated with high sensitivity to paclitaxel in v-Ha-ras-transformed NIH 3T3 fibroblasts.

We previously demonstrated that the downregulation of Raf-1 kinase may contribute to the development of acquired resistance in paclitaxel-resistant cells. In this study, we determine whether the sensitivities of parental and its v-Ha-ras-transformed NIH 3T3 cells to paclitaxel were dependent on Raf-1 kinase activity. Paclitaxel sensitivity of v-Ha-ras-transformed cells was found to be significantly higher than that of its parental cells.

Genotoxicity Studies on Carrageenan: Short-term Assays.

Carrageenan is a naturally-occurring sulfated polygalactan which has been widely used in the dairy industry and a gelling agent in non-dairy products. In this study, four short-term genotoxicity assays were investigated to evaluate the potential genotoxic effects of carrageenan. The mutagenic-ity of carrageenan was evaluated up to a maximum dose of 5 mg/plate in Ames test.

Studies on the Genotoxic Effects of Wood Smoke Flavors.

Smoke flavors based on the thermal decomposition of wood have been applied to a variety of food products as an alternative for traditional smoking. Despite its increasing use, the available genotoxicity data on wood smoke flavors (WSF) are still controversial. Thus, potential genotoxic effects of WSF in four short-term genotoxicity assays were investigated, which included the Ames assay, chromosomal aberration assay, micronucleus test and the alkaline comet assay.