Influence of cell cycle checkpoints and p53 function on the toxicity of temozolomide in human pancreatic cancer cells.

Background: Though an increased efficacy of carmustine and temozolomide (TMZ) has been demonstrated by inactivation of O(6)-methylguanine-DNA methyltransferase (MGMT) with O(6)-benzyl-guanine (BG) in human pancreatic tumors refractive to alkylating agents, the regulatory mechanisms have not been explored.

Methods: The effects of TMZ and BG on apoptosis, cell growth, the mitotic index, cell cycle distribution, and protein expression were studied by TUNEL, cell counting, flow cytometry, and Western blot analysis, respectively.

Results: The wt-p53 human pancreatic tumor cell line Capan-2 and p53-efficient mouse embryonic fibroblasts (MEFs) were more responsive to treatment with TMZ + BG than mutant p53 Capan-1 and p53-null MEFs.

Lack of P-glycoprotein expression by low-dose fractionated radiation results from loss of nuclear factor-kappaB and NF-Y activation in oral carcinoma cells.

Multidrug resistance (MDR) is associated with the overproduction of the 170-kDa transmembrane protein P-glycoprotein (MDR1) caused by transcriptional activation. However, the activity of the MDR1 promoter in response to different doses of ionizing radiation has not been investigated. In this study, two squamous cell carcinoma oral cavity cell lines, T-167 and T-409, were exposed to either a standard clinical dose of 2 Gy or low-dose fractionated radiation therapy (LDFRT), delivered as 0.

Rat model of polymicrobial infection, immunity, and alveolar bone resorption in periodontal disease.

One of the predominant polymicrobial infections of humans is expressed clinically as periodontal disease. Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia have been strongly implicated as members of a pathogenic consortium in the etiology of adult periodontitis. In this study we hypothesized that P.

Elevated sphingomyelinase activity and ceramide concentration in serum of patients undergoing high dose spatially fractionated radiation treatment: implications for endothelial apoptosis.

Spatially fractionated high dose (grid) radiation treatment (SFGRT) involves irradiation of bulky tumors with one high, grid-delivered, dose of 15 Gy followed by multiple consecutive doses of 2 Gy each. The goal of this study is to determine the effect of this treatment on serum ceramide content and to investigate possible involvement of ceramide in tumor regression after SFGRT. Serum ceramide and Secretory SMase (S-SMase) were quantified in 11 patients before and at 24, 48 and 72 h after the dose of 15 Gy.

Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3.

Curcumin (Diferuloylmethane) is a major chemical component of turmeric (curcuma longa) and is used as a spice to give a specific flavor and yellow color in Asian food. Curcumin exhibits growth inhibitory effects in a broad range of tumors as well as in TPA-induced skin tumors in mice. This study was undertaken to investigate the radiosensitizing effects of curcumin in p53 mutant prostate cancer cell line PC-3.

The impact of TNF-alpha induction on therapeutic efficacy following high dose spatially fractionated (GRID) radiation.

A variety of cytokines especially TNF-alpha and TGF-beta are known to be released in response to high dose radiation of tumors. However, these are not normally measurable in systemic circulation unless high levels of these cytokines are produced by tumor cells. This study was undertaken to see if circulating levels of these cytokines could be measured in the serum of patients treated with high dose spatially fractionated (GRID) radiation and to correlate the finding of these cytokines with clinical response to treatment.