What do we know about the α/β for prostate cancer?

Since last decade, the debate on the parameter which reflects prostate cancer sensitivity to fractionation in a radiotherapy treatment, the α/β, has become extensive. Unlike most tumors, the low labeling indices (LI) and large potential doubling time that characterize the prostate tumor led some authors to consider that it may behave as a late responding tissue. So far, the existing studies with regard to this subject point to a low value of α/β, around 2.7 Gy, which may be considered as a therapeutic gain in relation to surrounding normal tissues by using fewer and larger fractions. The aim of this paper is to review several estimates that have been made in the last few years regarding the prostate cancer α/β both from clinical and experimental data, as well as the set of factors that have potentially influenced these evaluations.

Alternative regimens for prostate cancer treatment using radiation therapy

Purpose/Objective: The purpose of this work was to determine biologically equivalent alternative regimens for the treatment of prostate cancer using External Beam Radiotherapy (EBRT) and Low Dose-Rate Brachytherapy (LDRBT) with 125I implants and to evaluate the sensitivity of these regimens to different sets of radiobiological parameters of the Linear-Quadratic (LQ) model.

Differential expression of CDC25 phosphatases splice variants in human breast cancer cells

Background: CDC25 phosphatases control cell cycle progression by activating cyclin dependent kinases. The three CDC25 isoforms encoding genes are submitted to alternative splicing events which generate at least two variants for CDC25A and five for both CDC25B and CDC25C. An over-expression of CDC25 was reported in several types of cancer, including breast cancer, and is often associated with a poor prognosis. Nevertheless, most of the previous studies did not address the expression of CDC25 splice variants. Here, we evaluated CDC25 spliced transcripts expression in anti-cancerous drug-sensitive and resistant breast cancer cell lines in order to identify potential breast cancer biomarkers. Methods: CDC25 splice variants mRNA levels were evaluated by semi-quantitative RT-PCR and by an original real-time RT-PCR assay. Results: CDC25 spliced transcripts are differentially expres-sed in the breast cancer cell lines studied. An up-regulation of CDC25A2 variant and an increase of the CDC25C5/C1 ratio are associated to the multidrug-resistance in VCREMS and DOXOR breast cancer cells, compared to their sensitive counterpart cell line MCF-7. Additionally, CDC25B2 tran-script is exclusively over-expressed in VCREMS resistant cells and could therefore be involved in the development of certain type of drug resistance. Conclusions: CDC25 splice variants could represent interesting potential breast cancer prognostic biomarkers.

Modulation of translation factor's gene expression by histone deacetylase inhibitors in breast cancer cells

The histone deacetylase inhibitors sodium butyrate (NaBu) and trichostatin A (TSA) exhibit anti-proliferative activity by causing cell cycle arrest and apoptosis. The mechanisms by which NaBu and TSA cause apoptosis and cell cycle arrest are not yet completely clarified, although these agents are known to modulate the expression of several genes including cell-cycle- and apoptosis-related genes. The enzymes involved in the process of translation have important roles in controlling cell growth and apoptosis, and several of these translation factors have been described as having a causal role in the development of cancer. The expression patterns of the translation mechanism, namely of the elongation factors eEF1A1 and eEF1A2, and of the termination factors eRF1 and eRF3, were studied in the breast cancer cell line MCF-7 by real-time quantitative reverse transcription-polymerase chain reaction after a 24-h treatment with NaBu and TSA. NaBu induced inhibition of translation factors' transcription, whereas TSA caused an increase in mRNA levels. Thus, these two agents may modulate the expression of translation factors through different pathways. We propose that the inhibition caused by NaBu may, in part, be responsible for the cell cycle arrest and apoptosis induced by this agent in MCF-7 cells.

Helical tomotherapy versus 3D conformal radiotherapy in dosimetric planning for patients with localized prostate cancer

Radiotherapy is one of the therapeutics selected for localized prostate cancer, in cases where the tumour is confined to the prostate, penetrates the prostatic capsule or has reached the seminal vesicles (T1 to T3 stages). The radiation therapy can be administered through various modalities, being historically used the 3D conformal radiotherapy (3DCRT). Other modality of radiation administration is the intensity modulated radiotherapy (IMRT), that allows an increase of the total dose through modulation of the treatment beams, enabling a reduction in toxicity. One way to administer IMRT is through helical tomotherapy (TH). With this study we intent to analyze the advantages of helical tomotherapy when compared with 3DCRT, by evaluating the doses in the organs at risk (OAR) and planning target volumes (PTV).

Statistical analysis of quality control measurements in IMRT for head and neck and prostate cancer

Intensity Modulated Radiotherapy (IMRT) is a technique introduced to shape more precisely the dose distributions to the tumour, providing a higher dose escalation in the volume to irradiate and simultaneously decreasing the dose in the organs at risk which consequently reduces the treatment toxicity. This technique is widely used in prostate and head and neck (H&N) tumours. Given the complexity and the use of high doses in this technique it’s necessary to ensure as a safe and secure administration of the treatment, through the use of quality control programmes for IMRT. The purpose of this study was to evaluate statistically the quality control measurements that are made for the IMRT plans in prostate and H&N patients, before the beginning of the treatment, analysing their variations, the percentage of rejected and repeated measurements, the average, standard deviations and the proportion relations.

Diethydithiocarbamate complexes with metals used as food suplements show diferente effects in cancer cells

Diethyldithiocarbamate (ditiocarb), a metabolite of the old anti-alcoholic drug disulfiram (Antabuse), forms proteasome-inhibiting metal complexes with copper or zinc that suppress cancer cells both in vitro and in vivo. The drug has been used in a clinical trial (NCT00742911) along with copper gluconate as a dietary supplement in patients with cancer spreading to the liver. In this study, we demonstrate the effect of synthetic complexes of disulfiram with four various metals (Mn, Fe, Cr and Cu) used as food supplements. These complexes may be spontaneously formed in the blood during the use of disulfiram with divalent metals and thus may suppress the growth of cancer in vivo. The cytotoxic effect of the compounds and the compounds' ability to inhibit the cellular proteasome were tested in the osteosarcoma cell line U2OS. After 48 h, copper and manganese complexes exhibited cytotoxic effect on the cell line, in sharp contrast to both iron and chromium complexes. (C) 2014 Faculty of Health and Social Studies, University of South Bohemia in Ceske Budejovice. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

New iron(II) cyclopentadienyl derivative complexes: synthesis and antitumor activity against human leucemia cancer cells

A new family of "Fe-II(eta(5)-C5H5)" half sandwich compounds bearing a N-heteroaromatic ligand coordinated to the iron center by a nitrile functional group has been synthesized and fully characterized by NMR and UV-Vis spectroscopy. X-ray analysis of single crystal was achieved for complexes 1 and 3, which crystallized in the monoclinic P2(1)/c and monoclinic P2(1)/n space groups, respectively. Studies of interaction of these five new complexes with plasmid pBR322 DNA by atomic force microscopy showed very strong and different types of interaction. Antiproliferative tests were examined on human leukemia cancer cells (HL-60) using the MTT assay, and the IC50 values revealed excellent antiproliferative activity compared to cisplatin. (C) 2014 Elsevier B.V. All rights reserved.

Bisphenol A alters transcript levels of biomarker genes for major depressive disorder in vascular endothelial cells and colon cancer cells

Bisphenol A (BPA) is capable of mimicking endogenous hormones with potential consequences for human health and BPA exposure has been associated with several human diseases including neuropsychiatric disorders. Here, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results show that BPA at low concentrations (10 ng/mL and 1 μg/mL) induces differential transcript levels of four biomarker genes for Major Depressive Disorder (MDD) in HT29 human colon adenocarcinona cell line and Human Umbilical Vein Endothelial Cells (HUVEC). These results substantiate increasing concerns of BPA exposure in levels currently detected in humans.

Bisphenol A at the reference level counteracts doxorubicin transcriptional effects on cancer related genes in HT29 cells

Human exposure to Bisphenol A (BPA) results mainly from ingestion of food and beverages. Information regarding BPA effects on colon cancer, one of the major causes of death in developed countries, is still scarce. Likewise, little is known about BPA drug interactions although its potential role in doxorubicin (DOX) chemoresistance has been suggested. This study aims to assess potential interactions between BPA and DOX on HT29 colon cancer cells. HT29 cell response was evaluated after exposure to BPA, DOX, or co-exposure to both chemicals. Transcriptional analysis of several cancer-associated genes (c-fos, AURKA, p21, bcl-xl and CLU) shows that BPA exposure induces slight up-regulation exclusively of bcl-xl without affecting cell viability. On the other hand, a sub-therapeutic DOX concentration (40nM) results in highly altered c-fos, bcl-xl, and CLU transcript levels, and this is not affected by co-exposure with BPA. Conversely, DOX at a therapeutic concentration (4μM) results in distinct and very severe transcriptional alterations of c-fos, AURKA, p21 and CLU that are counteracted by co-exposure with BPA resulting in transcript levels similar to those of control. Co-exposure with BPA slightly decreases apoptosis in relation to DOX 4μM alone without affecting DOX-induced loss of cell viability. These results suggest that BPA exposure can influence chemotherapy outcomes and therefore emphasize the necessity of a better understanding of BPA interactions with chemotherapeutic agents in the context of risk assessment.