Molecular and Cellular Oncology最新文献

In this study, we investigated the effects of an ethanolic extract of Mangifera indica L. kernel on the viability and proliferation of human lung cancer cells. We utilized MTT and BrdU cell proliferation assays, morphological assessments, cell cycle analyses, and apoptosis assays to investigate the extract's effects on lung cancer (A549 and NCI-H292) and normal lung (MRC-5) cells. The extract demonstrated a toxicity toward cancer cells compared to normal cells with dose-dependent anti-proliferative effect on lung cancer cells. The extract also caused differential effects on the cell cycle, inducing G0/G1 arrest and increasing the Sub-G1 population in both lung cancer and normal lung cells. Notably, the extract induced loss of membrane integrity, shrinkage, membrane blebbing, and apoptosis in lung cancer cells, while normal cells exhibited only early apoptosis. Furthermore, the extract exhibited higher toxicity towards NCI-H292 cells, followed by A549 and normal MRC-5 cells in decreasing order of potency. Our results suggest that the ethanolic extract of M. indica L. kernel has significant potential as a novel therapeutic agent for treating lung cancer cells, given its ability to induce apoptosis in cancer cell lines while causing minimal harm to normal cells.

Chordin (CHRD) is a secreted protein important in early development, yet a role for CHRD in human disease has not been identified. In this study we investigated CHRD in cancer and normal adult tissues using the wealth of genome-wide data available in public databases. We found that Chordin is amplified in the DNA of specific cancers such as lung squamous cell and others, although copy number variation did not strictly correlate with higher mRNA expression. In some cancers, such as renal and stomach carcinomas, increased CHRD expression significantly correlated with poor survival. In normal adult human tissues, CHRD mRNA was highest in hepatocytes. Crossveinless-2/BMPER, a component of the Chordin morphogenetic pathway expressed at the opposite side in embryos, was expressed in liver stellate cells. This raises the intriguing possibility that a BMP gradient might be established in the extracellular matrix of the space of Disse that surrounds portal sinusoid capillaries.

Poorly differentiated esophageal adenocarcinoma (PDEAC) has a dismal prognosis. Glypican-1(GPC-1) is known to be upregulated in several cancer types in contrast to healthy tissues, rendering it as a biomarker. Nevertheless, the potential therapeutic targeting of GPC-1 has not been explored in PDEAC. There is accumulating evidence that GPC-1, via upregulation of PI3K/Akt/ERK signaling, plays a crucial role in the progression and chemoresistance in cancer. Pictilisib, a class I pan PI3K inhibitor, has shown promising antitumor results in clinical trials, however, has not gained widespread success due to acquired drug resistance. This study investigated the role of GPC-1 in chemo-resistant PDEAC and appraises the impact of targeted silencing of GPC-1 on the antitumor effects of Pictilisib in PDEAC cell lines. Immunohistochemistry assays in PDEAC tissue specimens demonstrated a pronounced intensity of staining with GPC-1. Upregulation of GPC-1 was found to be correlated with advanced stage and poor prognosis. In-vitro studies examined the influence of GPC-1 knockdown and Pictilisib, both as individual agents and in combination, on cytotoxicity, cell cycle distribution, apoptosis, and gene expression profiles. Silencing GPC-1 alone showed significantly reduced cell viability, migration, colony formation, epithelial-mesenchymal transition, and stemness in PDEAC cells. Significantly, knockdown of GPC-1 combined with low-dose Pictilisib led to enhancement of cytotoxicity, cell cycle arrest, and apoptosis in ESO-26 and OE-33 cells. In the xenograft mouse model, the combination of Pictilisib and GPC-1 knockdown exhibited synergy. These findings suggest that GPC-1 represents a promising target to augment chemosensitivity in esophageal adenocarcinoma.

Growing evidence suggests that metavirome changes could be associated increased risk for malignant cell transformation. Considering Viruses have been proposed as factors for prostate cancer induction. The objective of this study was to examine the composition of the plasma metavirome of patients with prostate cancer. Blood samples were obtained from 49 male patients with primary prostate adenocarcinoma. Thirty blood donors were included as a control group. The obtained next-generation sequencing data were analyzed using a bioinformatic pipeline for virus metagenomics. Viral reads with higher abundance were assembled in contigs and analyzed taxonomically. Viral agents of interest were also confirmed by qPCR. Anelloviruses and the Human Pegivirus-1 (HPgV-1) were the most abundant component of plasma metavirome. Clinically important viruses like hepatitis C virus (HCV), cytomegalovirus and human adenovirus type C were also identified. In comparison, the blood donor virome was exclusively composed of torque teno virus types (TTV) types. The performed HPgV-1 and HCV phylogeny revealed that these viruses belong to commonly detected in Brazil genotypes. Our study sheds light on the plasma viral abundance in patients with prostatic cancer. The obtained viral diversity allowed us to separate the patients and controls, probably suggesting that malignant processes may influence virome composition. More complex and multiple approach investigations are necessary to examine the likely causal relationship between metavirome and its nvolvement in prostate cancer.

GBM is the most common and aggressive type of brain tumor. It is classified as a grade IV tumor by the WHO, the highest grade. Prognosis is generally poor, with most patients surviving only about a year. Only 5% of patients survive longer than 5 years. Understanding the molecular mechanisms that drive GBM progression is critical for developing better diagnostic and treatment strategies. Identifying key genes involved in GBM pathogenesis is essential to fully understand the disease and develop targeted therapies. In this study two datasets, GSE108474 and GSE50161, were obtained from the Gene Expression Omnibus (GEO) to compare gene expression between GBM and normal samples. Differentially expressed genes (DEGs) were identified and analyzed. To construct a protein-protein interaction (PPI) network of the commonly up-regulated and down-regulated genes, the STRING 11.5 and Cytoscape 3.9.1 were utilized. Key genes were identified through this network analysis. The GEPIA database was used to confirm the expression levels of these key genes and their association with survival. Functional and pathway enrichment analyses on the DEGs were conducted using the Enrichr server. In total, 698 DEGs were identified, consisting of 377 up-regulated genes and 318 down-regulated genes. Within the PPI network, 11 key up-regulated genes and 13 key down-regulated genes associated with GBM were identified. NOTCH1, TOP2A, CD44, PTPRC, CDK4, HNRNPU, and PDGFRA were found to be important targets for potential drug design against GBM. Additionally, functional enrichment analysis revealed the significant impact of Epstein-Barr virus (EBV), Cell Cycle, and P53 signaling pathways on GBM.

Genome sequenced samples from cancer patients helped identify roles of different mutation types and enabled targeted therapy development. However, critical questions like what are the gene mutation rates among the patients? or what genes are most commonly mutated, pan-cancer? have only been recently answered. Here, we highlight this recent advance.