Nitrogen cycling rates and light effects in tropical Lake Maracaibo, Venezuela

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109860/1/lno19984381814.pd

The cl2/dro1/ccdc80 null mice develop thyroid and ovarian neoplasias

We have previously reported that the expression of the CL2/CCDC80 gene is downregulated in human papillary thyroid carcinomas, particularly in follicular variants. We have also reported that the restoration of CL2/CCDC80 expression reverted the malignant phenotype of thyroid carcinoma cell lines and that CL2/CCDC80 positively regulated E-cadherin expression, an ability that likely accounts for the role of the CL2/CCDC80 gene in thyroid cancer progression. In order to validate the tumour suppressor role of the CL2/CCDC80 gene in thyroid carcinogenesis we generated cl2/ccdc80 knock-out mice. We found that embryonic fibroblasts from cl2/ccdc80(-/-) mice showed higher proliferation rate and lower susceptibility to apoptosis. Furthermore, cl2/ccdc80(-/-) mice developed thyroid adenomas and ovarian carcinomas. Finally, ret/PTC1 transgenic mice crossed with the cl2/ccdc80 knock-out mice developed more aggressive thyroid carcinomas compared with those observed in the single ret/PTC1 transgenic mice. Together, these results indicate CL2/CCDC80 as a putative tumour suppressor gene in human thyroid carcinogenesis

An Italian Multicenter Perspective Harmonization Trial for the Assessment of MET Exon 14 Skipping Mutations in Standard Reference Samples

Lung cancer remains the leading cause of cancer deaths worldwide. International societies have promoted the molecular analysis of MET proto-oncogene, receptor tyrosine kinase (MET) exon 14 skipping for the clinical stratification of non-small cell lung cancer (NSCLC) patients. Different technical approaches are available to detect MET exon 14 skipping in routine practice. Here, the technical performance and reproducibility of testing strategies for MET exon 14 skipping carried out in various centers were evaluated. In this retrospective study, each institution received a set (n = 10) of a customized artificial formalin-fixed paraffin-embedded (FFPE) cell line (Custom METex14 skipping FFPE block) that harbored the MET exon 14 skipping mutation (Seracare Life Sciences, Milford, MA, USA), which was previously validated by the Predictive Molecular Pathology Laboratory at the University of Naples Federico II. Each participating institution managed the reference slides according to their internal routine workflow. MET exon 14 skipping was successfully detected by all participating institutions. Molecular analysis highlighted a median Cq cut off of 29.3 (ranging from 27.1 to 30.7) and 2514 (ranging from 160 to 7526) read counts for real-time polymerase chain reaction (RT-PCR) and NGS-based analyses, respectively. Artificial reference slides were a valid tool to harmonize technical workflows in the evaluation of MET exon 14 skipping molecular alterations in routine practice

Total Nitrogen and Phosphorus From Tributary Rivers to the Lake of Maracaibo System, Venezuela

Nitrogen and phosphorus are primary nutrients, common constituents of fertilizers, detergents, and domestic and industrial wastewater discharges. These unloadings to rivers and subsequently to Lake Maracaibo cause nutrient and mineral enrichment, producing a secondary eutrophication on rivers and detained waters at deltas. Lake Maracaibo system is a basin of extraordinary importance because of its energetic resources, biodiversity and the wide number of aquatic organisms, which represents an important economic source for the country. However, activities being developed on the basin such as agricultural, cattle raising, mining and industrials, have modified the physical, chemical and biological characteristics of both water and soil generating an accelerated eutrophication process, as well as, the appearance of dense populations of the aquatic weed Lemna obscura, generating social, environmental and economic impacts. The following river basins were evaluated: Limón, Palmar, Santa Ana, Catatumbo, Escalante, Chama, Motatán, Misoa, Machango and Pueblo Viejo. These rivers contribute with 80% of the freshwater to the Lake Maracaibo system, being the Catatumbo river contribution 60% of the volume. Total nitrogen and total phosphorus average of rivers that drain to the Lake, was 1.20 and 0.84 mgl-1, respectively, contributing significantly with the process of eutrophication, that combined with the expansion of the agricultural borders, have caused deforestation, erosion and contamination, altering landscape and water availability, as well as an important increase of nutrients in Lake Maracaibo

Predictive biomarkers of immunotherapy for non-small cell lung cancer: Results from an Experts Panel Meeting of the Italian Association of Thoracic Oncology

Unleashing the potential of immune system to fight cancer has become one of the main promising treatment modalities for advanced non-small cell lung cancer (NSCLC). The knowledge of numerous factors that come into play in the cancer-immunity cycle provide a wide range of potential therapeutic targets, including monoclonal antibodies that inhibits the programmed death-1 (PD-1) checkpoint pathway. Over the last two years, nivolumab, pembrolizumab and atezolizumab received approval for treatment of pretreated advanced NSCLC, and more recently, immunotherapy with pembrolizumab is the new standard of care as first-line in patients with high levels of programmed death-ligand 1 (PD-L1) expression. Selection of patients is mandatory and PD-L1 is the only biomarker currently available in clinical practice. However, PD-L1 staining is an imperfect marker, whose negativity does not exclude a response to immunotherapy, as well as the roughly half of patients are "not-responders" despite high tumor PD-L1 levels. The right cut-off, the differences among various immune checkpoint inhibitors and among various antibody clones, and a not trivial activity reported even in PD-L1 negative tumors are questions still open. New biomarkers beyond to PD-L1 assays as well as new strategies, including combination of immune checkpoint inhibitors are under investigation

miR-191 down-regulation plays a role in thyroid follicular tumors through CDK6 targeting.

CONTEXT: Well-differentiated thyroid carcinomas include papillary (PTC) and follicular (FTC) carcinomas. FTC is usually a more aggressive form of cancer than the more common papillary type. miR-191 expression is frequently altered in several neoplasias, being up-regulated in some cases, such as pancreatic carcinomas, and down-regulated in other carcinomas, such as melanomas. OBJECTIVE: The objective was to evaluate the expression and the role of miR-191 in thyroid carcinogenesis. DESIGN: The expression of miR-191 was analyzed in tissues from patients with follicular adenoma (n = 24), FTC (n = 24), PTC (n = 15), anaplastic thyroid carcinoma (n = 8), and the follicular variant of PTC (n = 6) compared with normal thyroid tissues by quantitative RT-PCR. miR-191 expression was restored in the follicular thyroid cell line WRO, and the effects on cell proliferation, migration, and target expression were evaluated. RESULTS: miR-191 is down-regulated in follicular adenoma, FTC, and follicular variant of PTC. We identified CDK6, a serine-threonine kinase involved in the control of cell cycle progression, as a novel target of miR-191. Restoration of miR-191 expression in WRO cells reduces cell growth and migration rate on vitronectin. CDK6 overexpression, correlated with miR-191 down-regulation, was found in follicular adenoma and FTC, suggesting a role of miR-191 down-regulation in the generation of these neoplasias. CONCLUSIONS: Our results suggest that miR-191 down-regulation plays a role in thyroid neoplasias of the follicular histotype, likely by targeting CDK6

Effects of combined administration of rapamycin, tolvaptan, and AEZ-131 on the progression of polycystic disease in PCK rats

Both experimental and clinical studies have suggested that any potential treatment of polycystic kidney disease (PKD) should start early and last for a long time to be effective, with unavoidable side reactions and considerable costs. The aim of the present study was to test how low doses of rapamycin (RAPA; 0.15 mg/kg ip for 4 days/wk), tolvaptan (TOLV; 0.005% in diet), or AEZ-131 (AEZ; a novel ERK inhibitor, 30 mg/kg for 3 days/wk by gavage), alone and in association, affect the progression of polycystic renal disease in PCK rats. Rats were treated for 8 wk starting at 4-6 wk of age. The efficacy of low doses of such drugs in inhibiting their respective targets was confirmed by immunoblot experiments. Compared with rats in the control (CON) group, RAPA treatment caused a significant reduction in cyst volume density (CVD; -19% vs. the CON group) and was numerically similar to that in TOLV-treated rats (-18%, not significiant), whereas AEZ treatment was not effective. RAPA + TOLV treatment resulted in a significantly lower CVD (-49% vs. the CON group) and was associated with a striking decrease in cAMP response element-binding protein phosphorylation, and similar data were detected in RAPA + AEZ-treated rats (-42%), whereas TOLV + AEZ treatment had virtually no effect. RAPA administration significantly lessened body weight gain, whereas TOLV administration resulted a mild increase in diuresis and a significant increase in cAMP urinary excretion. Histological data of tubular proliferation were in full agreement with CVD data. In conclusion, this study demonstrates that the association of low doses of RAPA, TOLV, and AEZ slows the progression of PKD with limited side effects, suggesting the use of combined therapies also in clinical trials