Expression of CD133 in differentiated thyroid cancer of young patients

CD133 expression in cancer is frequently associated with poor outcome. Thyroid carcinomas are rare in childhood and adolescence and are associated with a higher risk of recurrence and more metastases than the adult tumours. The aim of the study was to assess whether the expression of CD133 in thyroid carcinomas of children, adolescents and young adults was correlated with clinical prognostic factors

Profils d'expression des gènes de l'apoptose (caspases et XIAP) impliqués dans la pathologie prostatique

Il existe 2 pathologies prostatiques principales : l hyperplasie prostatique bénigne (HPB) et le cancer. L apoptose est au centre des mécanismes physiopathologiques prostatiques. Pour l HPB, nous avons travaillé sur du tissu de patients traités par un inhibiteur de la 5 alpha réductase (Finastéride). Nous avons montré que l apoptose des cellules épithéliales était précoce (6-8 jours) et qu elle faisait intervenir la voie des caspases effectrices, elle-même activée par la voie mitonchondriale. Ce travail permet de mieux comprendre les mécanismes d induction de l apoptose du Finastéride. Pour le cancer de la prostate, nous avons étudié l étape effectrice de l apoptose sur du tissu tumoral et non tumoral provenant de mêmes patients. L expression de la molécule antiapoptotique XIAP est fortement augmentée dans la tumeur par rapport au tissu sain, alors que la caspase-3 activée est diminuée. Ces résultats suggèrent le rôle clé de l XIAP dans le cancer de la prostateThere are two main prostatic diseases: Benign Prostatic Hyperplasia (BPH) and cancer. Apoptosis has been identify to be the key mechanism in prostate pathology. To better understand prostate apoptosis, research on human prostatic tissues are needed. Firstly, we studied in prostate tissues from mens displaying BPH the mechanism of action of anti-androgens such as finasteride, which inhibits 5 alpha reductase, involved in the metabolisme of testosterone. The apoptotic process peaked after 6-8 days of treatment in epithelial prostatic cells and was linked to an activation of effector caspases and the mitochondrial pathway. Secondly, we study apoptosis on tumoral and non tumoral prostatic tissues from the same patients, to clear through inter-individual variations. We showed that XIAP was overexpressed in tumoral prostate tissues compared to their non-tumoral counterparts, whereas active caspase-3 levels were decreased. These results suggested the key role of XIAP in prostate cancerLYON1-BU.Sciences (692662101) / SudocSudocFranceF

MiR-7-5p inhibits thyroid cell proliferation by targeting the EGFR/MAPK and IRS2/PI3K signaling pathways

The aberrant expression of miRNAs is often correlated to tumor development. MiR-7-5p is a recently discovered downregulated miRNA in thyroid papillary carcinoma (PTC). The goal of this project was to characterize its functional role in thyroid tumorigenesis and to identify the targeted modulated pathways. MiR-7-5p overexpression following transfection in TPC1 and HT-ori3 cells decreased proliferation of the two thyroid cell lines. Analysis of global transcriptome modifications showed that miR-7-5p inhibits thyroid cell proliferation by modulating the MAPK and PI3K signaling pathways which are both necessary for normal thyroid proliferation and play central roles in PTC tumorigenesis. Several effectors of these pathways are indeed targets of miR-7-5p, among which EGFR and IRS2, two upstream activators. We confirmed the upregulation of IRS2 and EGFR in human PTC and showed the existence of a negative correlation between the decreased expression of miR-7-5p and the increased expression of IRS2 or EGFR. Our results thus support a tumor-suppressor activity of miR-7-5p. The decreased expression of miR-7-5p during PTC tumorigenesis might give the cells a proliferative advantage and delivery of miR-7-5p may represent an innovative approach for therapy.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Thyroid cancer: is the incidence rise abating?

OBJECTIVE: The aim of the present study was to determine recent trends in thyroid cancer incidence rates and to analyze histopathological characteristics and geographical distribution. METHODS: Histologically proven 5367 cases were collected over the period 1998-2006 in France from the Rhône-Alpes thyroid cancer registry. Geographical variations of incidence were analyzed using a mixed Poisson model. RESULTS: The average incidence rates, age standardized to the world population, were 3.9/100,000 in men and 12.3/100,000 in women, higher than those previously reported in France. After an initial increase during the first 3 years, a steady level of incidence was observed for the period 2001-2006. The annual incidence rate of microcarcinomas was correlated with that of all cancers in men and women (r=0.78 and 0.89; P<0.01) respectively. Papillary microcarcinomas represented 38% of tumors and two-thirds of them measured less than 5 mm in diameter. They were fortuitously discovered after thyroidectomy for benign diseases in 64% of cases. Histological marks of aggressiveness differed according to the size of the tumor. Despite recent advances in diagnosis, 13% of tumors were diagnosed at advanced stage especially in men. Geographical distribution of incidence based on subregional administrative entities showed lower incidence rates in rural than in urban zones in men (relative rate: 0.72; 95% CI: 0.62-0.84) and women (relative rate: 0.85; 95% CI: 0.73-0.93). CONCLUSION: The present study suggests that the rise in thyroid cancer incidence is now abating. It could reflect standardization in diagnostic procedures. Further studies, performed on a more prolonged period, are necessary to confirm these data

Prevalence of differentiated thyroid cancer in 810 cases of surgically treated goiter in Yemen.

<b>Background: </b> In 1990, the World Health Organization (WHO) suggested that severe iodine deficiency exists in Yemen. Therefore, we looked at the prevalence of differentiated thyroid goiter in 810 cases consecutive-ly treated by surgery for goiter. <b> Methods: </b> This was a retrospective study of 810 surgically operated cases of goiter over a 5-year period (1999-2003). All cases were evaluated on H&E stained sections from embedded, 10&#x0025; buffered formalin fixed tis-sue blocks. Special stains and immunohistochemical analysis were done in Yemen and abroad. Most patients were older than 20 years of age and were from the high altitude areas (2000 to 2600 meters above sea level), where iodine deficiency disorders (IDD) are well documented. <b> Results: </b> In the 810 cases, 729 (90&#x0025;) were females and the remaining 81 (10&#x0025;) were males, with female-to-male ratio of 9:1. Differentiated thy-roid cancer (DTC) was found in 170 (21&#x0025;) cases, including 148 (86.4&#x0025;) females and 22 (13.6&#x0025;) males. Nearly 60&#x0025; of the cases were in the age group of 21-40 years. Papillary carcinoma was the most common type of DTC (164 cases, 96.5&#x0025;). <b>Conclusions: </b> In a Yemeni population, which has a high prevalence of iodine deficiency, 21&#x0025; of patients operated on for nodular goiter without pre-operative fine needle aspiration biopsy had thyroid cancer, mostly of the papillary type. In this study, males and elderly patients with goiter had a higher chance of having malignancy

TM4SF1, A Novel Primary Androgen Receptor Target Gene Over-Expressed in Human Prostate Cancer and Involved in Cell Migration

International audienceBACKGROUND. The Androgen Receptor (AR) plays a key role in controlling prostate gland homeostasis and contributes to prostate carcinogenesis. The identification of its target genes should provide new candidates that may be implicated in cancer initiation and progression. METHODS. Transcriptomic experiments and chromatin immunoprecipitation were combined to identify direct androgen regulated genes. Real-time quantitative PCR (RT-qPCR) analyseswere performed tomeasure TM4SF1 mRNA levels in prostate cancer and benign prostatic hyperplasia (BPH) specimens. Immunohistochemicalmethodswere used to compare TM4SF1 protein expressionprofiles in the same cohort. AtargetedsiRNAs knockdown strategywas used, prior towound healing assays, to analyze the role of TM4SF1 in cell migration in vitro. RESULTS. We demonstrate for the first time that TM4SF1 is a direct target gene of the AR, a transcription factor of the steroidnuclear receptor family. A functional androgen response element was identified in the promoter region of the gene. In addition, TM4SF1 mRNA expression was higher in cancer samples compared to BPH tissues. The TM4SF1 protein mediates cell motility of prostate cancer cells where it is predominantly localized in the cytoplasm, in contrast to its apical membrane localization in normal prostate epithelial cells. CONCLUSIONS. Our results reveal a novel function for TM4SF1 in AR signaling. The TM4SF1 mRNA expression is higher in prostate cancer tissues as compared to BPH samples. Inhibition of cell migration after targeted knockdown of TM4SF1 protein expression suggests its contribution to prostate cancer cell metastasis. Prostate 71: 1239-1250, 2011. (C) 2011 Wiley-Liss, Inc

Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer

International audienceThe prostate-specific antigen (PSA) is the main diagnostic biomarker for prostate cancer in clinical use, but it lacks specificity and sensitivity, particularly in low dosage values 1. 'How to use PSA' remains a current issue, either for diagnosis as a gray zone corresponding to a concentration in serum of 2.5-10 ng/ml which does not allow a clear differentiation to be made between cancer and noncancer 2 or for patient follow-up as analysis of post-operative PSA kinetic parameters can pose considerable challenges for their practical application 3,4. Alternatively, noncoding RNAs (ncRNAs) are emerging as key molecules in human cancer, with the potential to serve as novel markers of disease, e.g. PCA3 in prostate cancer 5,6 and to reveal uncharacterized aspects of tumor biology. Moreover, data from the ENCODE project published in 2012 showed that different RNA types cover about 62% of the genome. It also appears that the amount of transcriptional regulatory motifs is at least 4.5x higher than the one corresponding to protein-coding exons. Thus, long terminal repeats (LTRs) of human endogenous retroviruses (HERVs) constitute a wide range of putative/candidate transcriptional regulatory sequences, as it is their primary function in infectious retroviruses. HERVs, which are spread throughout the human genome, originate from ancestral and independent infections within the germ line, followed by copy-paste propagation processes and leading to multicopy families occupying 8% of the human genome (note that exons span 2% of our genome). Some HERV loci still express proteins that have been associated with several pathologies including cancer 7-10. We have designed a high-density microarray, in Affymetrix format, aiming to optimally characterize individual HERV loci expression, in order to better understand whether they can be active, if they drive ncRNA transcription or modulate coding gene expression. This tool has been applied in the prostate cancer field (Figure 1)