Genetic Investigation of the Trail Mechanism in Diabetic and Non-diabetic Obese Patients.

Obesity is an important healthcare issue caused by abnormally increased adipose tissue because of energy-intake overcoming energy expenditure. Disturbances in the physiological function of adipose tissue mediate the development of diabetes. It is a metabolic disease that results from decreased insulin-levels and/or changes in the insulin action mechanism. Tumor Necrosis Factor-Associated Apoptosis-Inducing Ligand(TRAIL), which is a member of the Tumor Necrosis Factor(TNF)-family with an important role in adipose tissue biology, is included in many studies with its ability to induce apoptosis in cancer cells, but the number of human-studies conducted on the gene related to its protective-role against diabetes and obesity at this level is insufficient. Our study was carried out as a case and control and included three groups (80 diabetic obese, 80 non-diabetic obese, and 80 healthy individuals as the control group). The Real-Time-PZR(RT-qPZR), and DNA Sanger-Sequencing Methods were used for gene expression and gene squences. As a result of the analyses, TRAIL gene expression level was found to be higher in the controls than in the diabetic-obese and non-diabetic-obese group. This change in TRAIL gene expression suggests that TRAIL maybe a protective factor against diabetes. The presence of rs781673405, rs143353036, rs1244378045, rs767450259, rs759369504, rs750556128, and rs369143448 mutations, which was determined with the Sequencing-Method, was shown for the first time in the present study. In addition, it is the first study in which human TRAIL gene-expression and sequencing were performed together. We believe that these data will make an important contribution to the literature.

Interplay between Non-Coding RNAs and NRF2 in Different Cancers: Spotlight on MicroRNAs and Long Non-Coding RNAs.

Cancer is a multifactorial disease, and a wealth of information has enabled basic and clinical researchers to develop a better conceptual knowledge of the highly heterogeneous nature of cancer. Deregulations of spatio-temporally controlled transduction pathways play a central role in cancer progression. NRF2-driven signaling has engrossed significant attention because of its fundamentally unique features to dualistically regulate cancer progression. Context-dependent diametrically opposed roles of NRF2-induced signaling are exciting. More importantly, non-coding RNA (ncRNA) mediated regulation of NRF2 and interplay between NRF2 and ncRNAs have added new layers of complexity to already intricate nature of NRF2 signaling. There is a gradual enrichment in the existing pool of knowledge related to interplay between microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in different cancers. However, surprisingly, there are no clues about interplay between circular RNAs and NRF2 in various cancers. Therefore, future studies must converge on the functional characterization of additional important lncRNAs and circular RNAs, which regulated NRF2-driven signaling or, conversely, NRF2 transcriptionally controlled their expression to regulate various stages of cancer. SIGNIFICANCE STATEMENT: Recently, many researchers have focused on the NRF2-driven signaling in cancer progression. Excitingly, discovery of non-coding RNAs has added new layers of intricacy to the already complicated nature of KEAP1/NRF2 signaling in different cancers. These interactions are shaping the NRF2-driven signaling landscape, and better knowledge of these pathways will be advantageous in pharmacological modulation of non-coding RNA-mediated NRF2 signaling in various cancers.

Vitamin D increases the efficacy of cisplatin on bladder cancer cell lines.

BACKGROUND: 1,25(OH)2D3(Calcitriol), which is a broad regulatory molecule, plays a role in changing the efficacy of chemotherapeutic drugs. Cisplatin is one of a current standard chemotherapy regimen for bladder cancer. Increasing the effectiveness of the treatment and reducing the side effects to chemotherapeutics are of great importance in bladder cancer. We aimed to investigate the effect of the combination of cisplatin and calcitriol in order to create a possible advantage in treatment of bladder cancer. METHODS: T24, ECV-304 and HUVEC cell lines were treated with calcitriol and cisplatin individually and in combination. Dose determination and combination treatments of calcitriol and cisplatin were evaluated using the MTT assay for cytotoxicity analysis on the cells. Annexin V-PI staining method was used for apoptosis determination by flow cytometry. Also the P-gp expression levels were determined by flow cytometry. RESULTS: The combination treatment increased the anti-proliferative efficacy compared to the efficacy in cisplatin alone in T24 cells and reduced the cytotoxicity in the HUVEC healthy cells compared to cisplatin alone. Combination treatment achieved significantly higher apoptosis rate in T24 cells compared with the rates in treatment of cisplatin alone. However apoptosis decreased in HUVEC cell line. P-gp ratios were increased in HUVEC and decreased in T24 cells with combination treatment compared to the numbers in the control cells. The rate of apoptosis and P-gp levels showed no significant change in ECV-304 cells. CONCLUSION: Our study revealed that the combination of calcitriol and cisplatin allows the use of cisplatin at lower doses in T24 bladder cancer cell line.

Correlation between human colon cancer specific antigens and Raman spectra. Attempting to use Raman spectroscopy in the determination of tumor markers for colon cancer.

Colorectal cancer is the second most common cause of cancer-related deaths worldwide. To follow up on the progression of the disease, tumor markers are commonly used. Here, we report serum analysis based on Raman spectroscopy to provide a rapid cancer diagnosis with tumor markers and two new cell adhesion molecules measured using the ELISA method. Raman spectra showed higher Raman intensities at 1447 cm-1 1560 cm-1, 1665 cm-1, and 1769 cm-1, which originated from CH2 proteins and lipids, amide II and amide I, and CO lipids vibrations. Furthermore, the correlation test showed, that only the CEA colon cancer marker correlated with the Raman spectra. Importantly, machine learning methods showed, that the accuracy of the Raman method in the detection of colon cancer was around 95 %. Obtained results suggest, that Raman shifts at 1302 cm-1 and 1306 cm-1 can be used as spectroscopy markers of colon cancer.

Investigation of the effects of oxidative stress, inflammation on the pathway of tryptophan/kynurenine in OCD.

OBJECTIVES: Recent studies have shown that the distribution of the tryptophan/kynurenine pathway (KP) plays a role in the development of obsessive-compulsive disorder (OCD). We aimed to reveal the relationship between CYP1A1 rs464903 and aryl hydrocarbon receptor (AhR) rs10249788 associated with the KP and interferon gamma (IFN γ) and oxidative stress in OCD. METHODS: In our study, the serum and DNAs of 150 samples, including 100 OCD patients and 50 controls, were used. The activity of glutathione peroxidase (GSH-Px), and the levels of IFN γ, thiobarbituric acid reactive substances (TBARS), tryptophan, and kynurenine were determined by biochemical methods. AhR rs10249788 and cytochrome P450 family CYP1A1 rs4646903, which interact directly with the KP, were analysed by polymerase chain reaction followed by restriction fragment length polymorphism. P < 0.05 was considered statistically significant. RESULT: There were no significant differences between groups in CYP1A1 rs4646903 and AhR rs10249788 while tryptophan and IFN γ were found to be higher in controls (p < 0.001, for both), and TBARS and indolamine-2,3-dioxygenase were found to be higher in OCD (p < 0.001, for both). There were significant correlations between IFN γ and TBARS and GSH-Px (p = 0.028, p = 0.020, respectively) in the OCD group. CONCLUSIONS: For the first time studied in OCD, it has been shown that IFN γ, tryptophan, oxidative stress parameters, and gene variants of CYP1A1 rs4646903 anAhR rs10249788 are shown effective on the KP.

Anti-Mullerian Hormone Levels Increase After Bariatric Surgery in Obese Female Patients With and Without Polycystic Ovary Syndrome.

This study was aimed to investigate the effect of weight loss by bariatric surgery on the level of anti-Mullerian hormone (AMH) in morbidly obese female patients with or without polycystic ovary syndrome (PCOS). This prospective study includes 70 females, obese, and fertile patients of reproductive age. All patients were evaluated to determine the changes in weight, body mass index (BMI), serum AMH, and other biochemical parameters at the end of six months. The mean levels of the preop and postop AMH were 1.66±0.87 ng/ml and 5.99±1.39 ng/ml in the PCOS group; 1.35±0.76 ng/ml and 6.23±1.47 ng/ml in the non-PCOS group, respectively. The postop AMH levels were significantly higher than the preop levels for both groups (p<0.001). There were significant differences in the level of glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, total cholesterol, hemoglobin A1c, HOMA-IR, insulin between preop and postop 6th month. A negative correlation was found between postop AMH and body weight in all patients (r=-0.337, p=0.031). Postop AMH levels were negatively correlated with postop BMI levels in the non-PCOS patient group (r=-0.408, p=0.043). No significant difference was observed between the PCOS and non-PCOS groups in terms of all the parameters examined. In conclusion, our study suggests that the significantly increased AMH levels by losing weight with bariatric surgery in patients with morbid obesity with and without PCOS may indicate the improvement of fertilization potential. It could be considered when evaluating fertility in patients with morbid obesity.

Investigation of possible associations between tryptophan/kynurenine status and FOXP3 expression in colorectal cancer.

Tryptophan metabolism in the tumor microenvironment exerts immunosuppressive effects by affecting the anti-tumor functions of immune cells. The immunosuppressive roles of tryptophan and tryptophan metabolites and their effects on the FOXP3 gene, highly expressed in regulatory T cells (Tregs), are remarkable. Our study aimed to investigate the relation between tryptophan metabolism and the transcription factor FOXP3 gene in colorectal cancer (CRC). Patients with CRC (n = 159) and controls (n = 112) were included in the study. The FOXP3 rs3761548 variant genotyping from the isolated genomic DNA was performed by PCR-RFLP. FOXP3 gene expression was determined by Q-PCR in RNAs isolated from resected tissues at the same time. Serum tryptophan, kynurenine, kynurenic acid levels of the cases were determined by HPLC. In serum samples with CRC, tryptophan level was 14.32 ± 1.09 µmol/L, kynurenine level was 1.33 ± 0.02 µmol/L, and the kynurenic acid level was 0.01 ± 0.001 µmol/L. The level of tryptophan was found to be low in CRC compared to control (p < .001). In cases with CRC, CC genotype (p = .048) and C allele (p = .012) frequency for FOXP3 rs3761548 were higher than the control group. It was found that the expression level of the FOXP3 gene was approximately 44 times higher in the advanced tumor stage (T3 + T4) than in the early tumor stage (T1 + T2) (p = .021).We suggest that there may be a possible relationship among serum TRP, TRP metabolites (KYN, KYNA) levels, FOXP3 gene expression, and FOXP3 gene variants in CRC pathogenesis.

The role of cytokeratin 19 levels in the determination of endometriosis stages.

OBJECTIVE/AIM: Endometrisosis, one of the most common gynecological disease, is characterized by the presence of endometriotic tissue outside of uterine cavity. The development and the validation of a simple blood biomarker specific and sensitive for endometriosis may facilitate the rapid and the accurate diagnosis of the disease and thus early treatment. Cytokeratin expression changes during epithelial differentiation and this expression is important for the modulation and the control of cell cycle regulation, tumor cell motility and apoptosis. Cytokeratin 19 (CK-19) is expressed in most simple epithelial cells and their malignant counterparts. The aim of this study is to investigate serum CK-19 expression levels in patients with endometriosis and to determine the diagnostic role of CK-19 levels in differentiating various stage of endometriosis. METHODS: Ctytokeratin-19 expression and level were studied in 70 endometriosis patients and 50 volunteers by ELISA and RT-PCR. ROC analysis was performed by comparing all stages with each other and with the control group. RESULTS: The CK-19 levels were significantly higher in the endometriosis groups than that of the control group by ELISA and RT-PCR. A significant (p < .05) difference was observed in endometriosis patients according to the stages. CONCLUSION: Based on our data, it suggests that Cytokeratin-19 may have a potential role in the development of endometriosis.

MicroRNA regulation of TRAIL mediated signaling in different cancers: Control of micro steering wheels during the journey from bench-top to the bedside.

Large-scale sequencing methodologies have helped us identify numerous genomic alterations and we have started to scratch the surface of many new targets for treatment of cancer and the associated predictive biomarkers. TRAIL (TNF-related apoptosis-inducing ligand) is a highly appreciated anti-cancer molecule because of its ability to selectively target cancer cells. However, confluence of information suggests that cancer cells develop resistance against TRAIL-based therapeutics. It is being realized that overexpression of anti-apoptotic proteins and inactivation of pro-apoptotic proteins significantly impairs TRAIL triggered apoptosis, particularly in clinical settings. Re-balancing of pro-and anti-apoptotic proteins and upregulation of death receptors with functionally active extrinsic and intrinsic apoptotic pathways are necessary to sensitize cancer cells to TRAIL based therapeutics. microRNAs (miRNAs) are involved in regulation of myriad of molecular processes and characterized into oncogenic and tumor suppressor miRNAs. Accumulating data has identified miRNAs which positively or negatively regulate TRAIL mediated signaling in cancer cells, helping us understand different steps at which TRAIL-mediated apoptotic signaling can be targeted. Here, we assess the status of our understanding of the mechanisms related to miRNA regulation of TRAIL mediated signaling, as well as the existing gaps therein, and discuss the challenges and opportunities that will help us get closer to personalized medicine.

Synthesis, structural, cytotoxic and pharmacokinetic evaluation of some thiosemicarbazone derivatives.

Iron(III) and nickel(II) complexes bearing a thiosemicarbazone framework were synthesized by a one-pot synthesis method. The structures were characterized by elemental analysis, IR, 1 H NMR, APCI Mass, conductivity, magnetic moment measurements. Molecular and crystal structures of the iron(III) complex were obtained from single-crystal X-ray diffraction. The findings showed that the metal atom adopts a slightly distorted square-pyramidal coordination, with the four donor atoms of the thiosemicarbazone ligand defining the basal plane and a chloride atom occupying the apical position. In the crystal lattice, the structure is stabilized by intermolecular O─H···O and C─H···O interactions. The cytotoxic activity was studied by MTT assay, the expression levels of cytochrome P450 (CYP) enzymes by Western blot, and the lipophilicity (LogP) by using the shake-flask method, another pharmacokinetic parameter. The findings showed that the IC50 values decreased with the decrease of the LogP values of the substances. Cytochrome P450 expression levels were found specific for each compound and each cell line. As a result, the pharmacokinetic properties of the newly synthesized thiosemicarbazone compounds are crucial for oral administration and provide us with clues for prospective in vivo studies.

The effects of serum levels, and alterations in the genes of binding protein and receptor of vitamin D on gastric cancer.

Due to many biological cell functions of vitamin D including regulation of cell survival, proliferation and differentiation, the metabolism of itself gains importance in the development of several types of cancer. This case-control study was designed to evaluate the risk of gastric cancer development in terms of VDR rs2228570 & rs731236, and VDBP rs7041 polymorphisms, and serum levels of vitamin D. The study consists of 77 gastric cancer patients and 84 healthy individuals. VDR and VDBP gene polymorphisms and vitamin D levels were determined by using PCR-RFLP and HPLC methods. The distribution of VDR or VDBP gene variants were not different in study groups. The serum level of 25-hydroxyvitamin D was significantly lower in gastric cancer patients versus controls (16 ± 6 → 11 ± 6 ng/ml) in which male patients have higher levels than females. Although the whole study population lacks normal levels of 25-hydroxyvitamin D, it was found that the risk of the development of gastric cancer was approximately fourfold higher in cases with severe vitamin D (< 10 ng/ml) deficiency. Our results indicate that VDR rs731236 & rs2228570 or VDBP rs7041 polymorphisms were not risk factors for the development of gastric cancer individually, however, lower serum levels of vitamin D may be a contributory risk for both predisposition and development of gastric cancer.

Gene variants of TCF7L2 are histopathologically important in colorectal cancers but do not have direct association with MYC expression.

Rapidly accumulating preclinical and clinical studies have helped us to unveil underlying mechanisms of colorectal cancer development and progression. Deregulated signaling pathways play instrumental role in carcinogenesis, drug resistance and metastasis. Wnt signaling cascade has attracted considerable attention in colorectal cancer as many ground-breaking researches have highlighted central role of Wnt pathway in pathogenesis of colorectal cancer. T-Cell Transcription Factors (TCFs) have been shown to work synchronously with ß-catenin to fuel colorectal cancer development and progression. Chromatin immuno-precipitation coupled with high-throughput sequencing (ChIP-Seq) data sets has deepened our knowledge about critical role of risk-associated SNPs. Increasingly it is being reported that many risk-associated SNPs are located within binding sites for transcription factors and consequently risk status of these SNPs may modify binding pattern of transcriptional factors and thus rewire the transcriptional regulation. DNA was extracted from peripheral blood samples of 117 colorectal cancer patients and 127 healthy subjects. TCF7L2 variants (rs6983267, rs7903146) were examined by the PCR-RFLP method. Tumor and the surrounding tissues were dissected from 37 CRC patients and RNA isolation was performed. The gene expression of c-myc was determined by RT-PCR. T allele carriage of rs6983267 variant was found to be associated with CRC (p=0.042). TT genotype of rs7903146 was associated with late tumor stage (T3+T4) (p=0.037) and presence of mucinous component (p=0.031). TTCT haplotype was found to be statistically higher in CRC compared to the control group (p=0.007). There was no statistically significant difference in c-myc gene expression. TCF7L2 gene variants may play an important role in histopathologic aspects associated with CRC and it is independent of c-myc gene expression.

NEDD4 Family of E3 Ubiquitin Ligases in Breast Cancer: Spotlight on SMURFs, WWPs and NEDD4.

Massively parallel sequencing, genomic and proteomic technologies have provided near complete resolution of signaling landscape of breast cancer (BCa). NEDD4 family of E3-ubiquitin ligases comprises a large family of proteins particularly, SMURFs (SMURF1, SMURF2), WWPs and NEDD4 which are ideal candidates for targeted therapy. However, it is becoming progressively more understandable that SMURFs and NEDD4 have "split-personalities". These molecules behave dualistically in breast cancer and future studies must converge on detailed identification of context specific role of these proteins in BCa. Finally, we provide scattered clues of regulation of SMURF2 by oncogenic miRNAs, specifically considering longstanding questions related to regulation of SMURF1 and WWPs by miRNAs in BCa. SMURFS, WWPs and NEDD4 are versatile regulators and represent a fast-growing field in cancer research and better understanding of the underlying mechanisms will be helpful in transition of our knowledge from a segmented view to a more conceptual continuum.

Quercetin-mediated regulation of signal transduction cascades and microRNAs: Natural weapon against cancer.

Recent technological and analytical breakthroughs in genomics and proteomics have deepened our understanding related to the multifaceted nature of cancer. Because of therapeutically challenging nature of cancer, there has been a renewed interest in phytochemistry, and much attention is currently being given to the identification of signaling pathway inhibitors. Data obtained through high-throughput technologies has provided a broader landscape of wiring maps of complex oncogenic signaling networks, thus revealing novel therapeutic opportunities. Increasingly, it is being realized that although our knowledge related to physiological and pathophysiological roles of signal transduction cascades has evolved rapidly, the clinical development of signaling pathway inhibitors has been challenging. Quercetin has attracted considerable attention because of its amazingly high pharmacological value. Research over decades has sequentially shown that quercetin effectively inhibited cancer development and progression. In this review, we have attempted to set the spotlight on the regulation of different cell signaling pathways by quercetin. We partition this multicomponent review into how quercetin effectively regulates the Wnt/ß-catenin pathway, Janus kinase-signal transducer and activator of transcription pathway, and vascular endothelial growth factor/vascular endothelial growth factor receptor signaling cascade in different types of cancers. We also provide an overview of the regulation of NOTCH and SHH pathways by quercetin. MicroRNAs (miRNAs) have also emerged as versatile regulators of cancer, and contemporary studies have shed light on the ability of quercetin to control different miRNAs in various cancers. We have scattered information related to NOTCH and SHH pathways, and future studies must converge on the investigation of these pathways to see how quercetin modulates the signaling machinery of these pathways.

Piperlongumine as anticancer agent: The story so far about killing many birds with one stone.

Piperlongumine is a biologically and pharmacologically active constituent of the plant Piper longum. This compound is gradually gaining attention because of its ability to inhibit/prevent different cancers. Modern era of molecular oncology is incomplete without ground-breaking discoveries made in the field of cell signaling pathways. High-throughput technologies have considerably improved our understanding about wide ranging signal transduction cascades which play crucial role in cancer development and progression. It is exciting to note that piperlongumine has been shown to pleiotropically modulate different oncogenic signaling pathways. We partition this multi-component review into discrete sections and categorically summarize key findings related to excellent ability of piperlongumine to therapeutically target JAK-STAT, NF-kB and PI3K/AKT/mTOR pathways. We also set spotlight on regulation of TRAIL pathway and autophagy by piperlongumine in different cancers. On the basis of the current understanding of piperlongumine, molecular biologists and pharmacologists will develop the next generation of translational studies, which will prove to be helpful in improving the clinical outcome and getting a step closer to personalized medicine.

Interplay of long non-coding RNAs and TGF/SMAD signaling in different cancers.

Based on the exciting insights gleaned from decades of ground-breaking research, it has become evident that deregulated signaling pathways play instrumental role in cancer development and progression. Interestingly discovery of non-coding RNAs has revolutionized our understanding related to transcription, post-transcription and translation. Modern era has witnessed landmark discoveries in the field of molecular cancer and non-coding RNA biology has undergone tremendous broadening. There has been an exponential growth in the list of publications related to non-coding RNAs and overwhelmingly increasing classes of non-coding RNAs are adding new layers of complexity to already complicated nature of cancer. Regulation of TGF/SMAD signaling by miRNAs and LncRNAs has opened new horizons for therapeutic targeting of TGF/SMAD pathway. In this review we have set spotlight on central role of LncRNAs in modulation of TGF/SMAD pathway. Major proportion of the available evidence is underlining positive role of LncRNAs in contextual regulation of TGF/SMAD pathway. LncRNAs are vital to these regulatory networks because they provide a background support to make the TGF/SMAD mediated intracellular signaling more smooth or make transduction cascade more flexible in response to cues from extracellular environment. Therefore, in accordance with this notion, MALAT1, OIP5-AS1, MIR100HG, HOTAIR, ANRIL, PVT1, AFAP1-AS1, SPRY4-IT, ZEB2NAT, TUG1 and Lnc-SNHG1 have been reported to positively regulate TGF/SMAD signaling. In this review, we have focused on the regulation of TGF/SMAD signaling by LncRNAs and how these non-coding RNAs can be therapeutically exploited. Short-interfering RNA (siRNA) and natural products are currently being tested for efficacy against different LncRNAs. Nanotechnological strategies to efficiently deliver LncRNA-targeting siRNAs are also currently being investigated in different cancers.

The assessment of total antioxidant capacity and superoxide dismutase levels, and the possible role of manganese superoxide dismutase polymorphism in acromegaly.

Oxidative status is attributed to endothelial dysfunction and might be one of the key mechanisms of endothelial dysfunction in acromegaly. In this study, we aimed to investigate the effect of acromegaly on superoxide dismutase (SOD) and total antioxidant capacity (TAC) levels, and the possible influence of human manganese superoxide dismutase (MnSOD) polymorphism on these levels. 51 acromegaly patients and 57 age and sex matched healthy subjects were recruited to the study in Bezmialem Vakif University Hospital between 2011 and 2014. The median SOD and TAC levels were 42.7 (33-60) pg/mL and 1,313.7 (155-1,902) µM in acromegaly; and 46.3 (38-95) pg/mL and 1,607.3 (195-1,981) µM in healthy subjects (p < 0.001, p < 0.001). SOD levels were decreased in controlled and uncontrolled patients compared to healthy subjects (p = 0.05 and p = 0.002, respectively). Controlled and uncontrolled acromegaly displayed significantly decreased levels of TAC compared to healthy subjects (p < 0.05 and p < 0.001, respectively). SOD levels were not associated with MnSOD polymorphisms in acromegaly. In conclusion, this study showed that acromegaly was associated with decreased levels of SOD and TAC, and controlling the disease activity could not adequately improve these levels.

Expression of miR-373 and its predicted target genes E-cadherin and CD44 in patients with laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is a genomically complex disease that is difficult to target, and efforts have been made to identify new treatment strategies and   molecular markers that might stratify patients and individualize options for treatment. miR-373 has diametrically opposed roles in different stages and types of cancers. miR-373 has been suggested to quantitatively control E-cadherin and CD44 expression. We studied the expression of miR-373, E-cadherin and CD44 in laryngeal squamous cell carcinoma and evaluated the association between the disease and clinical characteristics of patients. Tumor tissues were collected from 24 laryngeal cancer patients. Adjacent normal tissue samples were also obtained as controls. After RNA isolation, we assessed the miR-373, E-cadherin and CD44 levels. As endogenous controls, we used the small RNA U6 and GAPDH TaqMan® to normalize the levels of expression of miR-373, E-cadherin and CD44. The fold change in the expression of the genes in larynx tumor and control tissues was calculated using the 2-ΔΔCT method. miR-373 was significantly upregulated in seventeen tumor samples compared to controls. However, the expression levels of both E-cadherin and CD44 mRNA were found to be significantly downregulated in tumor versus control regions (p=0.026 and p=0.005, respectively). We did not find any significant difference in the expression levels of miR-373, E-cadherin or CD44 and cancer risk factors. miR-373, E-cadherin and CD44 may be involved in the etiopathogenesis of laryngeal cancer. It can be suggested that E-cadherin and CD44 are functional targets of miR-373, but we need further studies to investigate this hypothesis.

Hepatocellular carcinoma: targeting of oncogenic signaling networks in TRAIL resistant cancer cells.

Apoptotic response in hepatocellular carcinoma (HCC) cells is impaired because of interconnectivity of proteins into complexes and signaling networks that are highly divergent in time and space. TNF-related apoptosis-inducing ligand (TRAIL) has emerged as an attractive anticancer agent reported to selectively induce apoptosis in cancer cells. Although diametrically opposed roles of TRAIL are reported both as an inducer of apoptosis and regulator of metastasis, overwhelmingly accumulating experimental evidence highlighting apoptosis inducing activity of TRAIL is directing TRAIL into clinical trials. Insights from TRAIL mediated signaling in HCC research are catalyzing new lines of study that should not only explain molecular mechanisms of disease but also highlight emerging paradigms in restoration of TRAIL mediated apoptosis in resistant cancer cells. It is becoming progressively more understandable that phytochemicals derived from edible plants have shown potential in modelling their interactions with their target proteins. Rapidly accumulating in vitro and in-vivo evidence indicates that phytonutrients have anticancer activity in rodent models of hepatocellular carcinoma. In this review we bring to limelight how phytonutrients restore apoptosis in hepatocellular carcinoma cells by rebalancing pro-apoptotic and anti-apoptotic proteins. Evidence has started to emerge, that reveals how phytonutrients target pharmacologically intractable proteins to suppress cancer. Target-based small-molecule discovery has entered into the mainstream research in the pharmaceutical industry and a better comprehension of the genetics of patients will be essential for identification of responders and non-responders.

Investigation of biomarker in laryngeal carcinomas.

BACKGROUND: The aim of the study is to determine whether there is a role of podoplanin and glutathione S-transferases T1 (GST-T1) expression in laryngeal squamous cell carcinoma. METHODS: In this study, 33 patients were enrolled and gene expression analysis was performed by qRT-PCR. The podoplanin and GST-T1 expression patterns were analyzed to determine their correlation with clinicopathologic parameters of laryngeal cancer. RESULTS: Of all included patients, 20 had supraglottic, and 13 had glottic laryngeal cancer. Increased expression of podoplanin was found in seven (35%) supraglottic tumor tissues and seven (53.8%) glottic tumor tissues, but GST-T1 expression was not detected. CONCLUSION: Podoplanin expression did not show any prediction for tumor differentiation, regional metastasis, thyroid cartilage invasion, lymphatic vessel invasion, or tumor differentiation for laryngeal cancer, and also there were no significant differences in podoplanin expression between glottic and supraglottic regions, but extracapsullar extension is almost statistically significance (P = 0.05).