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

Allevamento intensivo, in un sistema a circuito chiuso, di copepodi Calanoidi autoctoni come dieta viva alternativa per larvicoltura di specie ittiche marine

L’obiettivo generale del progetto è stato quello di sperimentare l’allevamento intensivo di due specie di copepodi Calanoidi autoctoni, Temora stylifera e Centropages typicus, utilizzando un impianto pilota a circuito chiuso e di impiegare le fasi larvali dei copepodi allevati come alimento vivo alternativo per larve di specie ittiche di interesse commerciale in sostituzione della dieta classica ad Artemia

Paralogous HOX13 Genes in Human Cancers

Hox genes (HOX in humans), an evolutionary preserved gene family, are key determinants of embryonic development and cell memory gene program. Hox genes are organized in four clusters on four chromosomal loci aligned in 13 paralogous groups based on sequence homology (Hox gene network). During development Hox genes are transcribed, according to the rule of “spatio-temporal collinearity”, with early regulators of anterior body regions located at the 3’ end of each Hox cluster and the later regulators of posterior body regions placed at the distal 5’ end. The onset of 3’ Hox gene activation is determined by Wingless-type MMTV integration site family (Wnt) signaling, whereas 5’ Hox activation is due to paralogous group 13 genes, which act as posterior-inhibitors of more anterior Hox proteins (posterior prevalence). Deregulation of HOX genes is associated with developmental abnormalities and different human diseases. Paralogous HOX13 genes (HOX A13, HOX B13, HOX C13 and HOX D13) also play a relevant role in tumor development and progression. In this review, we will discuss the role of paralogous HOX13 genes regarding their regulatory mechanisms during carcinogenesis and tumor progression and their use as biomarkers for cancer diagnosis and treatment

Accuracy of Fine Needle Cytology in Histological Prediction of Papillary Thyroid Carcinoma Variants: a Prospective Study

Fine needle cytology (FNC) is a crucial procedure in the preoperative diagnosis of thyroid tumors. Papillary thyroid carcinoma (PTC), in its classic variant (cPTC), is the most common malignant neoplasm of the thyroid. Several histological variants of PTC have been described, each one with its own characteristics and prognosis. The ability of FNC to identify the variants represents a challenge even for a skilled pathologist. The aim of this study was to evaluate the diagnostic cytological accuracy of FNC in PTC and to look for specific features that could predict the different variants. This was a single center prospective study on 128 patients who received a diagnosis of PTC on FNC. The smears were blindly reviewed by two cytopathologists to create a frequency score (0, 1, 2, 3) of the features for each variant. The cytological parameters were divided into three groups: architectural, nucleo-cytoplasmic, and background features. Univariate analysis was performed by chi-square test with Yates correction and Fisher exact test as appropriate. Multiple regression analysis was performed among the variables correlated at the linear correlation. The correlation study between cytology and histology showed an accuracy of FNC in classic, follicular, and oncocytic PTC variants of 63.5, 87.5, and 87% respectively. Familiarity with cytological features may allow an early diagnosis of a given PTC variant on FNC samples. This is fundamental in a preoperative evaluation for the best surgical approach and subsequent treatment

Epithelial-mesenchymal transition in prostate cancer: an overview

Prostate cancer is a main urological disease associated with significant morbidity and mortality. Radical prostatectomy and radiotherapy are potentially curative for localized prostate cancer, while androgen deprivation therapy is the initial systemic therapy for metastatic prostate disease. However, despite temporary response, most patients relapse and evolve into castration resistant cancer.Epithelial-mesenchymal transition (EMT) is a complex gradual process that occurs during embryonic development and/or tumor progression. During this process, cells lose their epithelial characteristics and acquire mesenchymal features. Increasing evidences indicate that EMT promotes prostate cancer metastatic progression and it is closely correlated with increased stemness and drug resistance.In this review, we discuss the main molecular events that directly or indirectly govern the EMT program in prostate cancer, in order to better define the role and the mechanisms underlying this process in prostate cancer progression and therapeutic resistance

Micrornas in prostate cancer: an overview

Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs' functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis

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

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

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

Accuracy of Fine Needle Cytology in Histological Prediction of Papillary Thyroid Carcinoma Variants: a Prospective Study

Fine needle cytology (FNC) is a crucial procedure in the preoperative diagnosis of thyroid tumors. Papillary thyroid carcinoma (PTC), in its classic variant (cPTC), is the most common malignant neoplasm of the thyroid. Several histological variants of PTC have been described, each one with its own characteristics and prognosis. The ability of FNC to identify the variants represents a challenge even for a skilled pathologist. The aim of this study was to evaluate the diagnostic cytological accuracy of FNC in PTC and to look for specific features that could predict the different variants. This was a single center prospective study on 128 patients who received a diagnosis of PTC on FNC. The smears were blindly reviewed by two cytopathologists to create a frequency score (0, 1, 2, 3) of the features for each variant. The cytological parameters were divided into three groups: architectural, nucleo-cytoplasmic, and background features. Univariate analysis was performed by chi-square test with Yates correction and Fisher exact test as appropriate. Multiple regression analysis was performed among the variables correlated at the linear correlation. The correlation study between cytology and histology showed an accuracy of FNC in classic, follicular, and oncocytic PTC variants of 63.5, 87.5, and 87% respectively. Familiarity with cytological features may allow an early diagnosis of a given PTC variant on FNC samples. This is fundamental in a preoperative evaluation for the best surgical approach and subsequent treatment