Dynamics of chromosomal aberrations, induction of apoptosis, BRCA2 degradation and sensitization to radiation by hyperthermia.

Hyperthermia can transiently degrade BRCA2 and thereby inhibit the homologous recombination pathway. Induced DNA-double strand breaks (DSB) then have to be repaired via the error prone non-homologous end-joining pathway. In the present study, to investigate the role of hyperthermia in genotoxicity and radiosensitization, the induction of chromosomal aberrations was examined by premature chromosome condensation and fluorescence in situ hybridisation (PCC-FISH), and cell survival was determined by clonogenic assay shortly (0-1 h) and 24 h following exposure to hyperthermia in combination with ionizing radiation.

The role of recent nanotechnology in enhancing the efficacy of radiation therapy.

Radiation therapy is one of the most commonly used non-surgical interventions in tumor treatment and is often combined with other modalities to enhance its efficacy. Despite recent advances in radiation oncology, treatment responses, however, vary considerably between individual patients. A variety of approaches have been developed to enhance radiation response or to counteract resistance to ionizing radiation.

Differential expression and sex chromosome association of CHD3/4 and CHD5 during spermatogenesis.

ATP-dependent nucleosome remodelers of the CHD family play important roles in chromatin regulation during development and differentiation. The ubiquitously expressed CHD3 and CHD4 proteins are essential for stem cell function and serve to orchestrate gene expression in different developmental settings. By contrast, the closely related CHD5 is predominantly expressed in neural tissue and its role is believed to be restricted to neural differentiation.

Inhibition of homologous recombination by hyperthermia shunts early double strand break repair to non-homologous end-joining.

In S and G2 phase mammalian cells DNA double strand breaks (DSBs) can potentially be repaired by homologous recombination (HR) or non-homologous end-joining (NHEJ). Results of several studies suggest that these two mechanistically distinct repair pathways can compete for DNA ends. Because HR and NHEJ differ with respect to error susceptibility, generation of chromosome rearrangements, which are potentially carcinogenic products of DSB repair, may depend on the pathway choice.

PCC and COBRA-FISH a new tool to characterize primary cervical carcinomas: to assess hall-marks and stage specificity.

A newly developed assay based on chemically induced premature chromosome condensation (PCC) and multi-color combined binary ratio labeling (COBRA) fluorescence in situ hybridization (FISH) techniques have been implemented in order to investigate for the first time for recurrent cytogenetic aberrations in primary cervical carcinoma (derived directly from biopsies) at different stages of progression. The cytogenetic profiles of 17 biopsies derived from 14 and 3 cervical cancer patients with squamous-cell carcinomas (Sq) and with adenocarcinomas (Ad), respectively, were assessed. Frequencies of both structural as well as numerical aberrations were found to be higher in Sq than in Ad.

Chromosome fragments have the potential to predict hyperthermia-induced radio-sensitization in two different human tumor cell lines.

Cellular radiosensitivity, assessed by loss of clonogenicity, has been shown to correlate with the number of radiation-induced chromosomal aberrations. Also an increased radiosensitivity by hyperthermia has been shown to correlate with an increase in chromosomal aberrations. Therefore, determination of the number of chromosomal aberrations might be used as an assay to predict the radiosensitivity of tumors pre-treated with hyperthermia at clinically relevant temperatures.

Effect of 41 degrees C and 43 degrees C on cisplatin radiosensitization in two human carcinoma cell lines with different sensitivities for cisplatin.

The effect of trimodality treatment consisting of hyperthermia, cisplatin and radiation was investigated in two cell lines with different sensitivities to cisplatin. Hyperthermia treatment was performed for 1 h at 41 degrees C and 43 degrees C in order to compare the effects of the two temperatures. Clonogenic assays were performed with cisplatin-sensitive SiHa human cervical carcinoma and cisplatin-resistant SW-1573 human lung carcinoma cell lines.