Identification of potential biomarkers for lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most predominant subtype of lung cancers and is one of the leading causes of cancer related mortality worldwide. Despite the advancements in the field of cancer diagnostics and therapeutics, detection at an early stage using reliable biomarkers is an unmet clinical need for a plethora of cancers, including LUAD, thus attributing to poor prognosis. In view of this, to identify potential biomarkers and therapeutic candidate genes, the expression of all known human genes was screened in the publicly available 'The Cancer Genome Atlas' (TCGA) samples of LUAD patients which resulted in the identification of overexpressed genes. Further analysis of these genes across various patient sample datasets revealed that ZNF687, ODR4, PBXIP1, PYGO2, METTL3, PIGM and RAD1 are consistently more highly expressed in LUAD. Higher expression of these genes either alone or in combination is correlated with poor survival of LUAD patients. Hence, in this study we propose that these identified genes could serve as potential candidates as gene signatures or biomarkers for LUAD that require further investigation in large cohorts of LUAD samples.

Assessment of azadirachtin-A, a neem tetranortritarpinoid, on rat spermatozoa during in vitro capacitation.

BACKGROUND: The exploration of the biological assessment of technical azadirachtin, a tetranortritarpinoid from the neem seed kernel, was reviewed. The present study was, therefore, designed to evaluate the dose-dependent in vitro effects of azadirachtin-A, particularly on the functional studies and determination of molecular events, which are critical in the process of sperm capacitation. METHODS: To assess the effects of the azadirachtin-A on the functional studies, sperm capacitation, the total sperm adenosine triphosphate levels, acrosome reaction (AR), the sperm-egg interaction and the determination of molecular events like cyclic adenosine-3',5'-monophosphate and calcium levels, the appropriate volumes of the sperm suspension were added to the medium to a final concentration of 1×106 sperm/mL and incubated in a humidified atmosphere of 5% CO2 in air at 37°C. The increasing quantities 0.5-2.0 mM/mL and the equivalent volumes of 50% dimethyl sulfoxide were added to the control dishes prior to the addition of spermatozoa and then observed at various time-points for motility and other analyses. RESULTS: Results revealed the dose- and time-dependent decrease in the functional consequence of capacitation, i.e. the percentage of motile spermatozoa, motility score and sperm motility index, levels of molecular events in spermatozoa, followed by declined spontaneous AR leading to lesser binding of the cauda epididymal sperm to the Zona pellucida. CONCLUSIONS: The findings confirm the inhibition of rat sperm motility by blocking some biochemical pathways like energy utilization. They also demonstrate that sperm capacitation is associated with the decrease in AR and that the levels of molecular events in spermatozoa can guide us towards the development of a new male contraceptive constituent.

SILAC-based quantitative proteomic analysis of gastric cancer secretome.

PURPOSE: Gastric cancer is a commonly occurring cancer in Asia and one of the leading causes of cancer deaths. However, there is no reliable blood-based screening test for this cancer. Identifying proteins secreted from tumor cells could lead to the discovery of clinically useful biomarkers for early detection of gastric cancer. EXPERIMENTAL DESIGN: A SILAC-based quantitative proteomic approach was employed to identify secreted proteins that were differentially expressed between neoplastic and non-neoplastic gastric epithelial cells. Proteins from the secretome were subjected to SDS-PAGE and SCX-based fractionation, followed by mass spectrometric analysis on an LTQ-Orbitrap Velos mass spectrometer. Immunohistochemical labeling was employed to validate a subset of candidates using tissue microarrays. RESULTS: We identified 2205 proteins in the gastric cancer secretome of which 263 proteins were overexpressed greater than fourfold in gastric cancer-derived cell lines as compared to non-neoplastic gastric epithelial cells. Three candidate proteins, proprotein convertase subtilisin/kexin type 9 (PCSK9), lectin mannose binding 2 (LMAN2), and PDGFA-associated protein 1 (PDAP1) were validated by immunohistochemical labeling. CONCLUSIONS AND CLINICAL RELEVANCE: We report here the largest cancer secretome described to date. The novel biomarkers identified in the current study are excellent candidates for further testing as early detection biomarkers for gastric adenocarcinoma.