, and as potential drug targets for radiosensitizing cancer cell lines.

Background And Purpose: Activation of some signaling pathways can promote cell survival and have a negative impact on tumor response to radiotherapy. Here, the role of differences in expression levels of genes related to the poly(ADP-ribose) polymerase-1 (PARP-1), heat shock protein 90 (Hsp90), B-cell lymphoma 2 (Bcl-2), and phosphoinositide 3-kinase (PI3K) pathways in the survival or death of cells following X-ray exposure was investigated.

Methods: Eight human cell cultures (MCF-7 and MDA-MB-231: breast cancers; MCF-12A: apparently normal breast; A549: lung cancer; L132: normal lung; G28, G44 and G112: glial cancers) were irradiated with X-rays.

Selective therapeutic benefit of X-rays and inhibitors of EGFR, PI3K/mTOR, and Bcl-2 in breast, lung, and cervical cancer cells.

Cancer continues to be a growing burden, especially in the resource limited regions of the world, and more effective and affordable therapies are highly desirable. In this study, the effect of X-ray irradiation and four inhibitors, viz. those against epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), mammalian target of rapamycin (mTOR) and B-cell lymphoma 2 (Bcl-2) was evaluated in lung, breast, and cervical cancer cell lines, including normal cell lines to determine and compare the potential therapeutic benefit of these treatment modalities.

The malignancy index is a robust predictor of prostate cancer.

The objective of this study was to validate the results from our published work and to test the robustness of our unique malignancy index as a (non-invasive) predictor of prostate cancer in fresh blood samples obtained from patients diagnosed with prostate cancer (PCa), benign prostatic hyperplasia (BPH), and healthy volunteers (Controls). The malignancy index was obtained by dividing the product of three biomarker values, [urokinase plasminogen activator (uPA), plasminogen activator inhibitor type-1 (PAI-1), and prostate-specific antigen (PSA)], by the age of the patient/healthy volunteer, using enzyme-linked immunosorbent (ELISA) assay methodology. The results confirmed earlier findings that the malignancy index discriminates prostate cancer from non-prostate cancer.

The malignancy index in plasma samples as a prostate cancer biomarker.

No unambiguous role of the involvement of uroplasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in prostate cancer has emerged, with current evidence suggesting that neither biomarker is likely of significant clinical value, save as an overall contributor. In this study, we attempt to discriminate prostate cancer from non-cancer in a cohort of plasma samples, using the Imubind ELISA assay. In this cohort, PAI-1 levels are higher in prostate cancer patients than healthy donors; uPA levels are higher in healthy donors than prostate cancer patients; and the uPA/PAI-1 ratio is higher in healthy donors than in prostate cancer patients.

Strong synergism between small molecule inhibitors of HER2, PI3K, mTOR and Bcl-2 in human breast cancer cells.

Targeting pro-survival cell signaling components has been promising in cancer therapy, but the benefit of targeting with single agents is limited. For malignancies such as triple-negative breast cancer, there is a paucity of targets that are amenable to existing interventions as they are devoid of the human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and estrogen receptor (ER). Concurrent targeting of cell signaling entities other than HER2, PR and ER with multiple agents may be more effective.

Profiling adrenal 11β-hydroxyandrostenedione metabolites in prostate cancer cells, tissue and plasma: UPC-MS/MS quantification of 11β-hydroxytestosterone, 11keto-testosterone and 11keto-dihydrotestosterone.

Adrenal C steroids serve as precursors to active androgens in the prostate. Androstenedione (A4), 11β-hydroxyandrostenedione (11OHA4) and 11β-hydroxytestosterone (11OHT) are metabolised to potent androgen receptor (AR) agonists, dihydrotestosterone (DHT), 11-ketotestosterone (11KT) and 11-ketodihydrotestosterone (11KDHT). The identification of 11OHA4 metabolites, 11KT and 11KDHT, as active androgens has placed a new perspective on adrenal C11-oxy C steroids and their contribution to prostate cancer (PCa).

Flow cytometry-assisted quantification of γH2AX expression has potential as a rapid high-throughput biodosimetry tool.

Large-scale radiological events require immediate and accurate estimates of doses received by victims, and possibly the first responders, to assist in treatment decisions. Although there are numerous efforts worldwide to develop biodosimetric tools to adequately handle triage needs during radiological incidents, such endeavours do not seem to actively involve sub-Saharan Africa which currently has a significant level of nuclear-related activity. To initiate a similar interest in Africa, ex vivo radiation-induced γH2AX expression in peripheral blood lymphocytes from fourteen healthy donors was assessed using flow cytometry.

In vitro radiosensitization by pentoxifylline does not depend on p53 status.

Purpose: The mode by which the xanthine derivative, pentoxifylline, induces a radiosensitizing effect in cell cultures is a key and controversial radiobiological issue and requires further elucidation.

Materials And Methods: Six human glioblastoma cell lines were tested for the effect of pentoxifylline treatment at maximum G2/M block on the basis of cell survival, mitotic activity, and micronucleus formation after exposure to gamma radiation. Cell survival was measured by the colony-forming assay.

Influence of p53 and bcl-2 on chemosensitivity in benign and malignant prostatic cell lines.

The administration of cancer chemotherapeutic agents results in an increase in the apoptotic cells in the tumor: therefore, it has been assumed that anticancer drugs exhibit their cytotoxic effects via apoptotic signaling pathways. Characteristics that confer sensitivity to drug-induced apoptosis are, a functional p53 protein and expression of the apoptosis-promoting protein, bax. The role of p53 and bax/bcl-2 in drug-induced apoptosis was assessed in six prostate cell lines, 1532T, 1535T, 1542T, 1542N, BPH-1 and LNCaP using TD(50) concentrations of etoposide, vinblastine and estramustine.

Inhibition of DNA repair by Pentoxifylline and related methylxanthine derivatives.

The methylxanthine drug Pentoxifylline is reviewed for new properties which have emerged only relatively recently and for which clinical applications can be expected. After a summary on the established systemic effects of Pentoxifylline on the microcirculation and reduction of tumour anoxia, the role of the drug in the treatment of vasoocclusive disorders, cerebral ischemia, infectious diseases, septic shock and acute respiratory distress, the review focuses on another level of drug action which is based on in vitro observations in a variety of cell lines. Pentoxifylline and the related drug Caffeine are known radiosensitizers especially in p53 mutant cells.

Studies on the influence of DNA repair on radiosensitivity in prostate cell lines.

The relationship between radiosensitivity and DNA repair was investigated in six human prostate cell lines, 1542-NPTX, BPH-1, 1542-CP(3)TX, 1532-CP(2)TX, 1535-CP(1)TX and LNCaP. Except for LNCaP, these cell lines are new and were derived from primary prostate tumours and normal non-tumourigenic prostate tissue. Cell survival was assessed by clonogenic assay.

Drug resistance in prostate cancer cell lines is influenced by androgen dependence and p53 status.

Chemotherapeutic drug resistance remains a significant obstacle in the control of prostate cancer. The influence of p53 and androgen status on the drug response of new cell lines from normal, benign and primary tumour epithelium was investigated. The prostate cell lines 1542-NPTX, BPH-1, 1542-CP(3)TX, 1532-CP(2)TX, 1535-CP(1)TX and LNCaP were exposed to TD(50) doses of etoposide, vinblastine and estramustine for a period of 24 h and re-incubated for a further 4 days before measuring the cell viability by crystal violet vital dye staining assay.