Correction: Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences.

[This corrects the article DOI: 10.18632/oncotarget.16725.].

Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences.

This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the world's leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease.

Role of DNA repair machinery and p53 in the testicular germ cell cancer: a review.

Notwithstanding the peculiar sensitivity to cisplatin-based treatment, resulting in a very high percentage of cures even in advanced stages of the disease, still we do not know the biological mechanisms that make Testicular Germ Cell Tumor (TGCT) "unique" in the oncology scene. p53 and MDM2 seem to play a pivotal role, according to several in vitro observations, but no correlation has been found between their mutational or expression status in tissue samples and patients clinical outcome. Furthermore, other players seem to be on stage: DNA Damage Repair Machinery (DDR) , especially Homologous Recombination (HR) proteins, above all Ataxia Telangiectasia Mutated (ATM), cooperates with p53 in response to DNA damage, activating apoptotic cascade and contributing to cell "fate". Homologous Recombination deficiency has been assumed to be a Germ Cell Tumor characteristic underlying platinum-sensitivity, whereby Poly(ADP-ribose) polymerase (PARP), an enzyme involved in HR DNA repair, is an intriguing target: PARP inhibitors have already entered in clinical practice of other malignancies and trials are recruiting TGCT patients in order to validate their role in this disease. This paper aims to summarize evidence, trying to outline an overview of DDR implications not only in TGCT curability, but also in resistance to chemotherapy.

Detection of predictive markers for therapeutic stratification of salivary glands tumors.

Malignant tumors of salivary glands are rare lesions, often with poor prognosis. At present, surgery represents the only therapeutic choice, whereas chemotherapy is employed as palliative treatment in advanced disease. Over the years several molecular alterations associated with the pathogenesis and progression of the salivary glands tumors have been well-characterized. Particularly, the mutational status and/or aberrant expression of certain markers, such as EGFR, HER2, cKIT, BRAF and AR, also identified in some tumor histotypes of the salivary glands, currently represent molecular targets for new and efficacious drugs routinely employed in the treatment of other neoplasias, such as breast, lungs, GIST and melanoma. The expression analysis of these biomarkers associated with histomorphological data, could then provide the oncologist the opportunity to create a proper stratification of patients for customized therapies. This review represents an overview of the lesions of the salivary glands best characterized in terms of molecular aspects, focusing the attention on those markers and molecular alterations which can be important in the diagnosis as well as in the therapeutic stratification of these tumors.

Hyperexpression of HOXC13, located in the 12q13 chromosomal region, in well­differentiated and dedifferentiated human liposarcomas.

Liposarcoma (LPS) is the most common soft tissue neoplasm in adults and is characterized by neoplastic adipocyte proliferation. Some subtypes of LPSs show aberrations involving the chromosome 12. The most frequent are t(12;16) (q13;p11) present in more than 90% of myxoid LPSs and 12q13-15 amplification in well-differentiated and dedifferentiated LPSs. In this region, there are important oncogenes such as CHOP (DDIT3), GLI, MDM2, CDK4, SAS, HMGA2, but also the HOXC locus, involved in development and tumor progression. In this study, we evaluated the expression of HOXC13, included in this chromosomal region, in a series of adipocytic tumors. We included 18 well-differentiated, 4 dedifferentiated, 11 myxoid and 6 pleomorphic LPSs as well as 13 lipomas in a tissue microarray. We evaluated the HOXC13 protein and gene expression by immunohistochemistry and quantitative PCR. Amplification/translocation of the 12q13-15 region was verified by FISH. Immunohistochemical HOXC13 overexpression was observed in all well-differentiated and dedifferentiated LPSs, all characterized by the chromosome 12q13-15 amplification, and confirmed by quantitative PCR analysis. In conclusion, our data show a deregulation of the HOXC13 marker in well­differentiated and dedifferentiated LPSs, possibly related to 12q13-15 chromosomal amplification.

Expression analysis of SPARC/osteonectin in oral squamous cell carcinoma patients: from saliva to surgical specimen.

Oral squamous cell carcinoma (OSCC) remains a significant cause of morbidity and mortality, with approximately 540,000 new cases annually worldwide. The molecular mechanisms related to the pathogenesis of this disease are still poorly understood. The discovery of a molecular marker that allows the early detection of this cancer, which can be easily identified in biological samples, such as saliva, without intervening in advanced stages, is a challenge. Numerous studies have identified a panel of molecular markers differently expressed in OSCC and normal oral mucosa. In particular, it was found an aberrant expression of matricellular glycoprotein SPARC. SPARC is involved in normal tissue remodeling, regulating the deposition of extracellular matrix, but also in neoplastic transformation. In fact, aberrant SPARC expression was detected both in stromal cells associated with cancer and in tumor cells. The aim of our study was the evaluation of SPARC on a retrospective series of 119 OSCC cases and the validation of the obtained data on a prospective series of 27 patients with OSCC, of whom we have previously collected saliva, and smeared material. The obtained results were correlated with each other and with clinical pathological parameters at our disposal. The study demonstrated a prognostic value of SPARC, especially with regard to its expression in the stroma surrounding OSCC (P < 0.05).