TRP genes family expression in colorectal cancer

Colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract. Different factors are responsible for the development of CRC. Transient Receptor Potential (TRP) which is an important component of calcium channel is associated with several pathological conditions like cancer, neurodegenerative and cardiovascular diseases. Thirty members of the family of TRP ion channel in mammals have been determined till now. The aim of this study is to investigate TRPM, TRPV and TRPC gene expression levels in tumor tissues of CRC patients and to analyze the relationship of expression in tumor tissue of CRC with other known prognostic factors. Material and Methods: In this study, 93 CRC patients were included. The level of TRP gene expression in paraffin blocks of normal and cancerous colorectal tissue samples were studied at the level of mRNA with Real-time PCR. Results: The mRNA expression level of TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 genes in 37 female and 56 male patients diagnosed with CRC was revealed lower in tumor tissue as compared to normal tissue (p < 0.05). No statistically significant differences of mRNA expression levels of other TRP genes were found. Conclusions: TRP gene family like TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 may be thought as potential genes contributing to tumorigenesis as their expression decreases in CRC as compared to normal tissues. Key Words: colorectal cancer, TRP genes family: TRPV3, TRPV4, TRPV5, TRPM4, TRPC6, mRNA expression

Prognostic impact of initial maximum standardized uptake value of 18F-FDG PET/CT on treatment response in patients with metastatic lung adenocarcinoma treated with erlotinib

Tulay Kus,1 Gokmen Aktas,1 Alper Sevinc,1 Mehmet Emin Kalender,1 Mustafa Yilmaz,2 Seval Kul,3 Serdar Oztuzcu,4 Cemil Oktay,5 Celaletdin Camci1 1Department of Internal Medicine, Division of Medical Oncology, Gaziantep Oncology Hospital, 2Department of Nuclear Medicine, 3Department of Biostatistics, Faculty of Medicine, 4Department of Medical Biology, Faculty of Medicine, University of Gaziantep, Gaziantep, 5Department of Radiology, Faculty of Medicine, University of Akdeniz, Antalya, Turkey Purpose: To investigate whether the initial maximum standardized uptake value (SUVmax) on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has a prognostic significance in metastatic lung adenocarcinoma.Patients and methods: Sixty patients (24 females, mean age: 57.9&plusmn;12 years) with metastatic stage lung adenocarcinoma who used erlotinib and underwent 18F-FDG PET/CT at the time of diagnosis between May 2010 and May 2014 were enrolled in this retrospective study. The patients were stratified according to the median SUVmax value, which was found as 11. Progression-free survival (PFS) rates for 3, 6, and 12&nbsp;months were examined for SUVmax values and epidermal growth factor receptor (EGFR) mutation status.Results: The number of EGFR-sensitizing mutation positive/negative/unknown was 26/17/17, respectively, and the number of patients using erlotinib at first-line, second-line, and third-line therapy was 15, 31, and 14 consecutively. The PFS rates of EGFR mutation positive, negative, and unknown patients for 3&nbsp;months were 73.1%, 35.3%, and 41.2% (P=0.026, odds ratio [OR]=4.39; 95% confidence interval [CI]: 1.45&ndash;13.26), respectively. The PFS rates of EGFR positive, negative, and unknown patients for 6&nbsp;months were 50%, 29.4%, and 29.4% (P=0.267, OR: 2.4; 95% CI: 0.82&ndash;6.96), respectively. The PFS rates of EGFR positive, negative, and unknown patients for 12&nbsp;months were 42.3%, 29.4%, 23.5% (P=0.408, OR: 2.0; 95% CI: 0.42&ndash;5.26), respectively. Thirty-one of 60 patients had SUVmax values &le;11. The PFS rates for 3, 6, and 12&nbsp;months were 70.5%/28% (P=0.001, OR=9.0; 95% CI: 2.79&ndash;29.04), 61.7%/8% (P&lt;0.001, OR=28.35; 95% CI: 5.5&ndash;143), and 52.9%/8% (P&lt;0.001, OR=18.69; 95% CI: 3.76&ndash;92.9) for low SUVmax (&le;11) group/high SUVmax (&gt;11) group, respectively.Conclusion: Initial SUVmax value on 18F-FDG PET/CT is found to be a prognostic factor anticipating the response to erlotinib for 3, 6, and 12-month rates of PFS in both EGFR-sensitizing mutation and wild-type tumor group. Keywords: lung adenocarcinoma, erlotinib, 18F-fluorodeoxyglucose positron emission tomography/computed tomography, maximum standardized uptake value, treatment response, prognosi

Polymorphism of CYP3A4 and ABCB1 genes increase the risk of neuropathy in breast cancer patients treated with paclitaxel and docetaxel

Tulay Kus,1 Gokmen Aktas,1 Mehmet Emin Kalender,1 Abdullah Tuncay Demiryurek,2 Mustafa Ulasli,1 Serdar Oztuzcu,3 Alper Sevinc,1 Seval Kul,4 Celaletdin Camci1 1Department of Internal Medicine, Division of Medical Oncology, University of Gaziantep, Gaziantep Oncology Hospital, Gaziantep, Turkey; 2Department of Medical Pharmacology, 3Department of Medical Biology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey; 4Department of Biostatistics, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey Background: Interindividual variability of pharmacogenetics may account for unpredictable neurotoxicities of taxanes. Methods: From March 2011 to June 2015, female patients with operable breast cancer who had received docetaxel- or paclitaxel-containing adjuvant chemotherapy were included in this study. All patients were treated with single-agent paclitaxel intravenously (IV) 175 mg/m2 every 3 weeks for four cycles, or IV 80 mg/m2 weekly for 12 cycles, and IV 100 mg/m2 docetaxel for four cycles as adjuvant treatment. We evaluated the relationship between neurotoxicity of taxanes and single-nucleotide polymorphisms of ABCB1, CYP3A4, ERCC1, ERCC2, FGFR4, TP53, ERBB2, and CYP2C8 genes. Taxane-induced neurotoxicity during the treatment was evaluated according to the National Cancer Institute Common Toxicity Criteria version 4.03 prior to each cycle. Chi-squared tests were used to compare the two groups, and multivariate binary logistic regression models were used for determining possible risk factors of neuropathy. Results: Pharmacogenetic analysis was performed in 219 females. ABCB1 3435 TT genotype had significantly higher risk for grade &ge;2 neurotoxicity (odds ratio [OR]: 2.759, 95% confidence interval [CI]: 1.172&ndash;6.493, P: 0.017) compared to TC and CC genotype, and also CYP3A4 392 AA and AG genotype had significantly higher risk for grade &ge;2 neurotoxicity (OR: 2.259, 95% CI: 1.033&ndash;4.941, P: 0.038) compared to GG genotype. For FDGF4 gene with AG and GG genotype, OR was 1.879 (95% CI: 1.001&ndash;3.525, P: 0.048) compared to AA genotype with regard to any grade of neuropathy risk. We could not find any other association of other genotypes with neurotoxicity grades. Conclusion: ABCB1 3435 TT genotype and CYP3A4 392 AA/AG genotypes may be used as predictors of neurotoxicity during taxane chemotherapy. Keywords: neurotoxicity, docetaxel, paclitaxel, CYP3A4, ABCB1, single nucleotide polymorphism

Polymorphisms in the MTHFR gene are associated with recurrence risk in lymph node-positive breast cancer patients

Ali Suner,1 Hakan Buyukhatipoglu,1 Gokmen Aktas,1 Tulay Kus,1 Mustafa Ulaslı,2 Serdar Oztuzcu,2 Mehmet Emin Kalender,1 Alper Sevinc,1 Seval Kul,3 Celaletdin Camci1 1Division of Medical Oncology, Department of Internal Medicine, Gaziantep Oncology Hospital, University of Gaziantep, Gaziantep, Turkey; 2Department of Medical Biology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey; 3Department of Biostatistics, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey Purpose: The aim of this study is to clarify the relationship between recurrence risk of breast cancer and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms.Patients and methods: Breast cancer patients who had undergone surgery in Gaziantep University Oncology Hospital between June 2005 and June 2012 were followed-up and retrospectively enrolled in this study. Blood samples were collected from all patients to assess MTHFR C677T polymorphisms. Stage according to tumor&ndash;node&ndash;metastasis system, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 status, grade of disease, menopausal status, and administered chemotherapy or hormonal therapy were recorded. Effects of these parameters on recurrence risk were evaluated using univariate analysis and multivariate binary logistic regression model.Results: Association of MTHFR C677T polymorphisms with recurrence risk was evaluated in 298 patients whose median age was 47&nbsp;years (range: 21&ndash;79&nbsp;years). In all patients, age (odds ratio [OR] =0.953, P=0.005) and N3 lymph node status (OR =6.293, P=0.001) were found to affect the recurrence risk. While MTHFR homozygote genotype did not have an effect on recurrence risk in all patients, increased risk was observed in lymph node-positive subgroup (OR&nbsp;=4.271; 95% CI 1.515&ndash;12.023; P=0.006). Adjusting for age, tumor size (T), and node status (N), MTHFR homozygote genotype had more statistically significant risk for recurrence (OR =3.255; 95% CI 1.047&ndash;10.125; P=0.041).Conclusion: MTHFR TT genotype was found to be associated with increased recurrence risk in patients with lymph node-positive breast cancer. Keywords: breast cancer, methylenetetrahydrofolate reductase, MTHFR, rs9651118 polymorphism, recurrence ris

Effect of Verapamil and Lidocaine on TRPM and NaV1.9 Gene Expressions in Renal Ischemia-Reperfusion

Conclusion. Our study suggested that verapamil and lidocaine significantly reduce the degree of ischemia-reperfusion injury due to effects to TRPM and Nav1.9 genes

TRP GENES FAMILY EXPRESSION IN COLORECTAL CANCER

Colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract. Different factors are responsible for the development of CRC. Transient Receptor Potential (TRP) which is an important component of calcium channel is associated with several pathological conditions like cancer, neurodegenerative and cardiovascular diseases. Thirty members of the family of TRP ion channel in mammals have been determined till now. The aim of this study is to investigate TRPM, TRPV and TRPC gene expression levels in tumor tissues of CRC patients and to analyze the relationship of expression in tumor tissue of CRC with other known prognostic factors. Material and Methods: In this study, 93 CRC patients were included. The level of TRP gene expression in paraffin blocks of normal and cancerous colorectal tissue samples were studied at the level of mRNA with Real-time PCR. Results: The mRNA expression level of TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 genes in 37 female and 56 male patients diagnosed with CRC was revealed lower in tumor tissue as compared to normal tissue (p < 0.05). No statistically significant differences of mRNA expression levels of other TRP genes were found. Conclusions: TRP gene family like TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 may be thought as potential genes contributing to tumorigenesis as their expression decreases in CRC as compared to normal tissues. Key Words: colorectal cancer, TRP genes family: TRPV3, TRPV4, TRPV5, TRPM4, TRPC6, mRNA expression