Identification of copy number alternation profiles in metastatic oral squamous carcinoma patients by using microarray-based comparative genomic hybridization: A study on Turkish patients.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is a severe form of cancer affecting different anatomic sites of the oral cavity. OSCC ranks as the sixth most common cancer type with an increasing prevalence globally. However, the mechanisms of OSCC process at later stages are not well understood. In this study, we aimed to determine genetic alternations in metastatic OSCC patients to identify genomic changes occurred at metastatic phase of the disease. MATERIAL AND METHODS: The Illumina CytoSNP-12 Array was used to determine copy number variations in OSCC cancer genome. Hybridization procedures were performed according to the manufacturer procedures (Illumina). Arrays were scanned on iScan System (Illumina). Data were analyzed using Illumina Genotyping module of Genome Studio software (version 1.2, Illumina). Multiple CNV algorithms and copy number alternations were accessed by Genome Studio. CNVs in whole genome were investigated by using a chromosomal heat map. RESULTS: We reported that gains in 8q21.11-ter, 9p21.3, 13q14.11-ter, 13q13.3-ter and losses in 5q14.3-ter, 5q35 and 17p13.3-12 were associated with the development of OSCC. In addition, we also detected that deletion in 2q33.2-ter and 2q35-37.3 regions were also associated with OSCC metastasis process. CONCLUSIONS: Our results were also showed that gains in 11q13.3-q13.4 and 2q13.2 chromosomal regions could promote the metastatic OSCC process. We believe that results of the study will help to find new biomarkers for diagnosis at later stage of OSCC.

A comprehensive bibliometric overview: antibiotic resistance and Escherichia coli in natural water.

The environment is the most important reservoir for both resistance mechanisms and gene transfer in biological science studies. This study gives a bibliometric overview of studies of "antibiotic resistance" and "Escherichia coli" in the field of "Agricultural and Biological Sciences" from 2015 to 2019 to assess both research trends and scholarly networks in diverse research disciplines. The two keywords of "antibiotic resistance" and "Escherichia coli" were selected to search in the Scopus database. Each review article was categorized into materials, natural waters (i.e., seawater, freshwater) and wastewater, journal name, and quartile in category of the journal, the year of publication, and the country. Bibliometric indicators and visualization maps were utilized to analyse the retrieved data quantitatively and qualitatively. A total of 1376 publications in the field of agricultural and biological sciences over the last 5 years were obtained using the keywords of antibiotic resistance and Escherichia coli. With additional keywords of freshwater and wastewater, 4 and 24 studies were obtained, respectively. Wastewater was found to be the most common working environment for the keywords of antibiotic resistance and Escherichia coli. It is also found that the studies of antibiotic resistance are mainly conducted in wastewater environments, focusing on human and food health. Working under "One Health" consisting of human, animal and agriculture, and environmental health could be the only permanent and effective approach to solving antibiotic resistance-related issues.

Apoptotic and genomic effects of corilagin on SKOV3 ovarian cancer cell line.

Corilagin is a member of the tannin family and has been isolated from traditional Chinese medicinal plants, such as Phyllanthus spp. Corilagin has anti-inflammatory, antioxidative, antiatherogenic, and antihypertensive effects in various experimental models. In this research, we aimed to investigate for the first time whether corilagin had apoptotic and genomic effects in ovarian cancer treatment in the same study. The potential apoptotic of corilagin was investigated using a WST1 cell proliferation test, caspase 3, and mitochondrial membrane potential JC1 assays in a time- and dose-dependent manner. Genomic changes in expression levels against corilagin treatment were measured using an Illumina human HT-12V4 BeadChip microarray. Bioinformatic data analyses were performed using GenomeStudio and Ingenuity Pathway Analysis software. The data of our study demonstrated that there were statistically significant time- and dose-dependent increases in caspase 3 enzymatic activity and loss of mitochondrial membrane potential in line with decreases in cancer cell proliferation. According to gene-ontology analysis, we found that adherens junctions, antigen processing and presentation, and the phosphatidylinositol signaling system were the most statistically significant networks in response to corilagin treatment on SKOV3 cells, in a time- and dose-dependent manner. The apoptotic and genome-wide effects of corilagin on ovarian cancer cells were examined in detail for the first time in the literature. The results of our study suggest that corilagin might have the potential to be used as a new treatment option for epithelial ovarian cancer.

Apoptotic Effects of Quercitrin on DLD-1 Colon Cancer Cell Line.

Quercetin, which is the most abundant bioflavonoid compound, is mainly present in the glycoside form of quercitrin. Although different studies indicated that quercitrin is a potent antioxidant, the action of this compound is not well understood. In this study, we investigated whether quercitrin has apoptotic and antiproliferative effects in DLD-1 colon cancer cell lines. Time and dose dependent antiproliferative and apoptotic effects of quercitrin were subsequently determined by WST-1 cell proliferation assay, lactate dehydrogenase (LDH) cytotoxicity assay, detection of nucleosome enrichment factor, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and also the localization of phosphatidylserine (PS) in the plasma membrane. There were significant increases in caspase-3 activity, loss of MMP, and increases in the apoptotic cell population in response to quercitrin in DLD-1 colon cancer cells in a time- and dose-dependent manner. These results revealed that quercitrin has antiproliferative and apoptotic effects on colon cancer cells. Quercitrin activity supported with in vivo analyses could be a biomarker candicate for early colorectal carcinoma.

Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer.

BACKGROUND AND AIMS: Quercitrin (QR; quercetin-3-O-rhamnoside) has been used previously as an antibacterial agent and has been shown to inhibit the oxidation of low-density lipoproteins and prevent an allergic reaction. Furthermore, it was demonstrated that quercitrin exerts protective effects against H2O2-induced dysfunction in lung fibroblast cells. However, the mechanisms of quercitrin effects on cancer cell proliferation and apoptosis is not well understood. The aim of this study is to investigate the cytotoxic and apoptotic effects of quercitrin and the molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer (NSCLC) cell lines. METHODS: Time- and dose-dependent antiproliferative and apoptotic effects of quercitrin determined by WST-1 cell proliferation assay, lactate dehydrogenase (LDH) cytotoxicity assay, determination of nucleosome enrichment factor, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and also the localization of phosphatidylserine in the plasma membrane. Changes in whole genome gene expression levels were examined by Illumina Human HT-12v4 beadchip microarrays. RESULTS: There were significant increases in caspase-3 activity, loss of MMP, and increases in apoptotic cell population in response to quercitrin in A549 and NCI-H358 NSCLC cells in a time- and dose-dependent manner. CONCLUSION: Our results demonstrated that genes involved in leukocyte transendothelial migration, cell adhesion and phosphatidylinositol signaling system pathways were the most statistically significant pathways in NCI-H358 and A549 cells. These results revealed that quercitrin has antiproliferative and apoptotic effects on lung cancer cells by modulating the immune response. After confirming its anticarcinogenic effects in vivo, quercitrin could be a novel and strong anticancer agent against NSCLC.

Identification of gene variants associated with hypoxia pathway in acute coronary syndrome: a pilot study.

Hypoxic condition is known to play an important role in the development of acute coronary syndrome (ACS) and understanding mechanism of hypoxic effects is essential to develop new treatment strategies for ACS. Based on the phenotypic features of cardiovascular diseases, it is claimed that genetic factors play an important role in the development genome-wide association studies have been studied to clarify the molecular mechanisms underlying heritable and prevalent phenotype. The claim was to investigate possible roles of gene polymorphisms involving in hypoxia pathway on ACS in this pilot study. DNA samples of 100 ACS cases and 100 controls from a Department of Cardiology, Istanbul University, were genotyped with Illumina CytoSNP-12 BeadChip 300 K Array. The additive model used for statistical analysis, and Correlation/Trend Test selected as a statistical process. It was determined different criteria for association analysis as case/control and number of plugged vessels. P value calculated with each SNP and score generated with -log10(P). Also, hypoxia pathway analysis was applied to find statistically significant genes. As a result of bioinformatic analysis, it was claimed that PIAS4 (rs735842) and VEGFA (rs699947) were the most statistically significant variants associated in hypoxia pathway analysis. Due to the information of literature, there have been no prior studies of possible interactions of hypoxia pathways the etiology of acute coroner syndromes in the same research. Detailed studies with larger sample groups are necessary to clarify the role of hypoxia in the development of disease.

The role of components of the extracellular matrix and inflammation on oral squamous cell carcinoma metastasis.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) accounts for about 90% of malignant oral lesions, and is identified as the most frequently occurring malignant tumour of oral structures. We aimed to investigate the genes and pathways related with metastasis on Turkish OSCC patients. MATERIALS AND METHODS: We performed whole genome expression profiling array on an Illumina platform. A total of 24 samples with 12 OSCC and 12-paired controls that had no tumour were included in the study. Hierarchic clustering and heat map were used for data visualisation and p-values assessed to identify differentially expressed genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Ingenuity Pathway Systems (IPA) analysis were performed to consider biologic meaning of differential expression of the genes between tumour and control groups. RESULTS: We identified 790 probe sets, corresponding to 648 genes that were effective in separating invasive and metastatic OSCC. Consequently, we found statistically relevant expression results on extracellular matrix members on MMPs such as MMP3, MMP10, MMP1 and MMP9; on laminin such as LAMC2, LAMA3 and LAMB3; several genes in the collagen family; and also on chemokines from the inflammation process. CONCLUSION: Statistically relevant expression changes for MMPs, laminins, collagens, and chemokines, which are components of the extracellular matrix and inflammation process, may be considered as a molecular biomarker for early prediction. Further studies are necessary to determine and understand the molecular mechanisms that underlie OSCC metastasis.

New indication for therapeutic potential of an old well-known drug (propranolol) for multiple myeloma.

PURPOSE: Propranolol, a non-selective ß-adrenergic receptor blocker, has been used for the treatment of the patients with hypertension for more than 50 years. There are several in vitro and in vivo evidences that ß-adrenergic receptor antagonists inhibit proliferation and angiogenesis and also increase apoptosis in breast, skin, and colon cancers. The aim of this study was to investigate the cytotoxic and apoptotic effects of propranolol and the genes involved in propranolol-induced apoptosis in multiple myeloma cells. METHODS: Time-dependent antiproliferation and apoptotic effects of propranolol were subsequently determined by MTT cell proliferation assay, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP), and also the localization of phosphatidylserine in the plasma membrane. Changes in expression levels of NF-ΚB pathway were examined by qRT-PCR array. RESULTS: IC50 values of propranolol on U266 cells were calculated as 141, 100, and 75 µM after 24-, 48-, and 72-h propranolol exposure, respectively. There were significant increases in caspase-3 activity, loss of MMP, and increases in apoptotic cell population in response to propranolol in U266 cells in a time- and dose-dependent manner. There were increases in expression levels of BCL10, TRAF family members, interleukins, TLR1-4, TNFRSF10B, NF-κB, and the inhibitors of NF-κB genes, and significant decreases in expression levels of Bcl-2 in response to propranolol treatment were observed. CONCLUSION: These results revealed that propranolol has antiproliferative and apoptotic effects on multiple myeloma cells. Being supported with in vivo analyses, propranolol can be a good and economical way to treat multiple myeloma patients.

DNA repair gene variants in endometrial carcinoma.

Several polymorphisms in the DNA repair gene are thought to have significant effects on cancer risk. In this study, we investigated the association of the polymorphisms in the DNA repair genes, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, and HOGG1 Ser326Cys, with endometrium cancer risk. Two hundred and sixty-two women were included in the study. Endometrial biopsy was performed, and on the basis of diagnosis and histological examination, women were divided into two groups: a control group (n=158) and an endometrial cancer group (n=104). Genotypes were determined by PCR-RFLP assays in endometrial carcinoma patients and age-matched controls. In this study, we found that the frequencies of Glu+ and Asp/Glu genotypes in APE, Gln/Gln genotype of XRCC1, Met/Met genotype of XRCC3, Cys+ and Ser/Cys genotypes of HOGG1, His+ and Asp/His genotypes of XPG, and Gln+ and Gln/Gln genotypes of XPD are more prevalent in patients than controls. Frequencies of Thr/Thr genotype in XRCC3 were increased in controls compared with patients and seem to be protected from endometrial cancer. Our findings suggest that XRCC1, XRCC3, XPD, XPG, APE1, and HOGG1 genetic variants may be associated with endometrial cancer in Turkish women.