Early expression of the Helicase-Like Transcription Factor (HLTF/SMARCA3) in an experimental model of estrogen-induced renal carcinogenesis

BACKGROUND: The Helicase-Like Transcription Factor (HLTF/SMARCA3) belongs to the family of SWI/SNF proteins that use the energy of ATP hydrolysis to remodel chromatin in a variety of cellular processes. Several SWI/SNF genes are disrupted in cancer, suggesting a role of tumor suppressor. Similarly, the HLTF gene was recently found to be inactivated by hypermethylation in a number of advanced colon and gastric tumors. However, other evidences indicated a 20-fold HLTF overexpression in cell lines derived from various neoplasms (ovary, breast, cervix, kidney...). RESULTS: In the present study, we investigated HLTF expression by immunohistochemistry in a model of kidney tumors induced by continuous administration of diethylstilbestrol to male Syrian golden hamsters. A strong labeling was already detected in small tumor buds, making HLTF an early cancer marker in this model. Although every cell stained for HLTF at this early stage, the number of HLTF-positive cells decreased to 10% with cancer progression, and these positive cells were dispersed in the tumor mass. HLTF expression was conserved in the HKT-1097 cell line established from kidney tumors, but again only 10% of positive cells were found in xenografts produced by HKT-1097 cells in nude mice. CONCLUSION: In conclusion, our data suggest that HLTF gene activation is linked to initial steps of carcinogenesis in this model and should be investigated in early stages of other neoplasms

The Src inhibitor dasatinib accelerates the differentiation of human bone marrow-derived mesenchymal stromal cells into osteoblasts

The proto-oncogene Src is an important non-receptor protein tyrosine kinase involved in signaling pathways that control cell adhesion, growth, migration and differentiation. It negatively regulates osteoblast activity, and, as such, its inhibition is a potential means to prevent bone loss. Dasatinib is a new dual Src/Bcr-Abl tyrosine kinase inhibitor initially developed for the treatment of chronic myeloid leukemia. It has also shown promising results in preclinical studies in various solid tumors. However, its effects on the differentiation of human osteoblasts have never been examined.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Tyrosinase related protein 1 (TYRP1/gp75) in human cutaneous melanoma

Melanoma prognosis is based on specific pathological features at the primary lesion. In metastatic patients, the extent of lymph node involvement is also an important prognosis indicator. Many progression markers both in tissues and serum, including circulating tumor cells, have been studied and new molecular markers are awaited from high-throughput screenings to discriminate between clinical stages and predict disease progression.The present review focuses on human tyrosinase related protein 1 also known as gp75 glycoprotein (Tyrp1/gp75), a melanosomal protein involved in the pigmentary machinery of the melanocyte and often used as differentiation marker, with a special emphasis on its emerging roles in the malignant melanocyte and melanoma progression. © 2011 Federation of European Biochemical Societies.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Étude de la valeur pronostique de la protéine p16 exprimée par le virus HPV dans les carcinomes épidermoïdes de la tête et du cou -- Dentisterie

info:eu-repo/semantics/nonPublishe

Saliva pepsin level of laryngopharyngeal reflux patients is not correlated with reflux episodes

Objective: To investigate the relationship between the laryngopharyngeal reflux (LPR) episodes at the multichannel intraluminal impedance-pH monitoring (MII-pH) and the concentration of pepsin in the saliva of LPR patients. Methods: Patients with LPR were enrolled from the polyclinic of Poitiers, France. Patients benefited from 24-hour MII-pH that allowed a correlation study between reflux episodes and symptoms. Patients reported the occurrence of the critical symptoms during the testing period through a recording device. Simultaneously, they collected a first saliva sample 30 minutes after the symptoms and a second saliva collection a few hours after the first collection. The patient symptoms were assessed with reflux symptom score (RSS). The relationship between pepsin concentration in the saliva, symptoms, and the reflux episode characteristics at the MII-pH was investigated through multiple linear regression. Results: A total of 65 patients with LPR were recruited. The mean concentrations of the first and the second pepsin samples were 92.0 ± 108.1 and 101.8 ± 131.0, respectively. Peptest (RD Biomed, Milan, Italy) was positive in 51 LPR patients (78.5%). Concentrations of both pepsin samples were significantly correlated (P = 0.019). There was no significant association between pepsin concentrations in saliva samples, RSS, key symptoms during the test period, and MII-pH findings. Conclusion: The level of pepsin saliva concentration is not associated with the reflux episodes at the MII-pH. Future studies are needed to better understand the relationship between the extracellular pepsin concentration, mucosal inflammation, and related laryngopharyngeal symptoms. Level of Evidence: 4 Laryngoscope, 2019.SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe

Involvement of macrophage migration inhibitory factor in cancer and novel therapeutic targets (Review)

Macrophage migration inhibitory factor (MIF) was originally identified in 1966 by Bloom and Bennett as a pro-inflammatory cytokine involved in the inhibition of macrophage motility. Since then, studies have investigated the functional contribution of this pro-inflammatory cytokine in several immune diseases, including rheumatoid arthritis and lupus erythematous. Recently, MIF has been reported to be involved in a variety of neoplastic diseases. The present review discusses previous cancer research studies that have investigated the involvement of MIF in carcinogenesis, disease prognosis, tumor cell proliferation and invasion, and tumor-induced angiogenesis. Finally, potential therapeutic approaches based on the use of MIF antagonists and neutralizing antibodies are examined. The review concludes that MIF could be a good prognostic biomarker in several types of cancer, but also that the inhibition of MIF could represent a novel therapy against cancer.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Hormone therapy for breast cancer, with an emphasis on the pure antiestrogen fulvestrant: Mode of action, antitumor efficacy and effects on bone health

Breast cancer is a major health problem in women of developed Western countries. Whereas estrogen receptor (ER) may be involved in many cases in breast carcinogenesis, its expression in breast tumors may predict a favorable response to hormone therapy. In this review, we report the role played by ER in breast cancer and compare the effects and mechanisms of action of partial (tamoxifen) and pure (fulvestrant) antiestrogens, as well as of aromatase inhibitors. Moreover, as ER also has a critical role in bone metabolism, we review the beneficial and adverse effects of breast cancer hormone therapy on bone health, with a particular emphasis on fulvestrant, the only pure antiestrogen recently approved by the FDA for Phase III clinical trials. We conclude that, because of its therapeutic efficacy and its seemingly minimal effect on bone integrity, fulvestrant represents a new option for the hormonal treatment of breast cancer that deserves further clinical evaluation.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Galectins and carcinogenesis: Their role in head and neck carcinomas and thyroid carcinomas

Head and neck cancers are among the most frequently occurring cancers worldwide. Of the molecular drivers described for these tumors, galectins play an important role via their interaction with several intracellular pathways. In this review, we will detail and discuss this role with specific reference to galectins-1,-3, and-7 in angiogenesis, cell proliferation, and invasion as well as in cell transformation and cancer progression. Furthermore, we will evaluate the prognostic value of galectin expression in head and neck cancers including those with oral cavity, salivary gland, and nasopharyngeal pathologies. In addition, we will discuss the involvement of these galectins in thyroid cancers where their altered expression is proposed as a new diagnostic biomarker.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Serum proteomics the use of albumin and globulin depletion improves the detection of new markers potentially related to breast cancer cell-induced osteolysis

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Immune Cell Density Evaluation Improves the Prognostic Values of Staging and p16 in Oropharyngeal Cancer

The incidence of oropharyngeal cancers (OPSCCs) has continued to rise over the years, mainly due to human papillomavirus (HPV) infection. Although they were newly reclassified in the last TNM staging system, some groups still relapse and have poor prognoses. Based on their implication in oncogenesis, we investigated the density of cytotoxic and regulatory T cells, macrophages, and Langerhans cells in relation to p16 status, staging and survival of patients. Biopsies from 194 OPSCCs were analyzed for HPV by RT-qPCR and for p16 by immunohistochemistry, while CD8, FoxP3, CD68 and CD1a immunolabeling was performed in stromal (ST) and intratumoral (IT) compartments to establish optimal cutoff values for overall survival (OS). High levels of FoxP3 IT and CD1a ST positively correlated with OS and were observed in p16-positive and low-stage patients, respectively. Then, their associations with p16 and TNM were more efficient than the clinical parameters alone in describing patient survival. Using multivariate analyses, we demonstrated that the respective combination of FoxP3 or CD1a with p16 status or staging was an independent prognostic marker improving the outcome of OPSCC patients. These two combinations are significant prognostic signatures that may eventually be included in the staging stratification system to develop personalized treatment approaches.SCOPUS: ar.jinfo:eu-repo/semantics/publishe