The amino-acid stress sensing eIF2α kinase GCN2 is a survival biomarker for malignant mesothelioma.

Background: Malignant mesothelioma is a tumour that is strongly associated with a history of asbestos exposure, and which derives from mesothelial cells that line the serous cavities of the body. The tumour most commonly arises in the pleural cavity, but can also arise in the pericardium, peritoneum, and tunica vaginalis. At present the lesion has a very poor prognosis and is an incurable form of cancer with median survival times of up to 19 months being quoted for some histological subtypes.

Multimodality Characterization of Cancer-Associated Fibroblasts in Tumor Microenvironment and Its Correlation With Ultrasound Shear Wave-Measured Tissue Stiffness in Localized Prostate Cancer.

Introduction: Growing evidence suggests that the tumor microenvironment (TME) represented by cellular and acellular components plays a key role in the multistep process of metastases and response to therapies. However, imaging and molecular characterization of the TME in prostate cancer (PCa) and its role in predicting aggressive tumor behavior and disease progression is largely unexplored. The study explores the PCa TME through the characterization of cancer-associated fibroblasts (CAFs) using both immunohistochemistry (IHC) and genomics approaches.

Gene expression in colorectal neoplasia: modifications induced by tissue ischaemic time and tissue handling protocol.

Aims: The heterogeneity within individual distinct cancer types in terms of behaviour, response to therapy and prognosis is well recognized. A major goal of translational research projects has therefore been to define clinically significant subgroups of individual tumour types by analysis of mRNA as well as protein expression. An essential premise of such investigations is that expression of these key molecules is a true reflection of conditions present within the neoplastic cells in vivo.

Seliciclib (CYC202, R-roscovitine) enhances the antitumor effect of doxorubicin in vivo in a breast cancer xenograft model.

We sought to determine whether seliciclib (CYC202, R-roscovitine) could increase the antitumor effects of doxorubicin, with no increase in toxicity, in an MCF7 breast cancer xenograft model. The efficacy of seliciclib combined with doxorubicin was compared with single agent doxorubicin or seliciclib administered to MCF7 cells and to nude mice bearing established MCF7 xenografts. Post-treatment cells and tumors were examined by cell cycle analysis, immunohistochemistry and real-time PCR.

Lesions resembling Langerhans cell histiocytosis in association with other lymphoproliferative disorders: a reactive or neoplastic phenomenon?

Langerhans cell histiocytosis (LCH) has been described in association with a variety of neoplasms preceding, after, or synchronous with the other tumor. In some cases, a neoplasm may arise as a complication of therapy for LCH, and in others, the association may be coincidental. Synchronous occurrence has been reported most commonly in association with malignant lymphoma in which discrete proliferations of Langerhans cells (LCs) histologically indistinguishable from LCH are seen.

Activity of MDI-301, a novel synthetic retinoid, in xenografts.

The efficacy of MDI-301, a non-toxic novel synthetic retinoid, was found to be equivalent to the natural 9-cis-retinoic acid (RA) in vitro against estrogen-dependent MCF7 and T47D breast cancer cell lines which express RA receptor (RAR) alpha. Both retinoids also showed similar efficacy against established PC-3 prostate carcinoma xenografts. MCF7 tumor xenografts showed a reduction in tumor growth of 48% without systemic side-effects upon treatment with MDI-301 compared with MCF7 controls.

Mutations of APC, K-ras, and p53 are associated with specific chromosomal aberrations in colorectal adenocarcinomas.

It is widely accepted that both large-scale chromosomal abnormalities and mutation of specific genes, such as APC, K-ras, and/or p53, occur in the majority of colorectal adenocarcinomas. Whether or not a relationship exists between these different forms of genetic abnormalities was previously unknown. Using comparative genomic hybridization and mutational analysis of APC, K-ras, and p53 to evaluate 50 colorectal adenocarcinomas, we have shown that mutation of p53 is significantly associated with gain of 20q, 13q, and 8q and loss of 18q (P = 0.

Signaling to p53: the use of phospho-specific antibodies to probe for in vivo kinase activation.

Phospho-specific antibody technology has been recently adopted to study p53 phosphorylation both in vivo and in vitro. We have developed and carefully characterized p53 phosphospecific reagents directed to major amino- and carboxy-terminal regulatory sites. The specificities of both polyclonal and monoclonal reagents targeting the same phospho-epitope are discussed.

Alteration of glutathione S-transferase levels in Barrett's metaplasia compared to normal oesophageal epithelium.

Objective: Oesophageal cancer associated with the premalignant condition Barrett's oesophagus has increased in incidence over the last few years. Phase II detoxifying enzymes, including glutathione S-transferases (GSTs) protect the mucosa from carcinogens, which can cause oxidative damage to cells. Therefore, a reduction in these anti-oxidant enzymes can increase the risk of carcinogenesis.