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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–node–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 47years (range: 21–79years). 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=4.271; 95% CI 1.515–12.023; 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 1.047–10.125; 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 risk

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 ≥2 neurotoxicity (odds ratio [OR]: 2.759, 95% confidence interval [CI]: 1.172–6.493, P: 0.017) compared to TC and CC genotype, and also CYP3A4 392 AA and AG genotype had significantly higher risk for grade ≥2 neurotoxicity (OR: 2.259, 95% CI: 1.033–4.941, P: 0.038) compared to GG genotype. For FDGF4 gene with AG and GG genotype, OR was 1.879 (95% CI: 1.001–3.525, 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 polymorphisms

Gokmen Aktas,1 Tulay Kus,1 Mehmet Emin Kalender,1 Alper Sevinc,1 Celaletdin Camci,1 Seval Kul2 1Division of Medical Oncology, Department of Internal Medicine, School of Medicine, Gaziantep Oncology Hospital, Gaziantep University, Gaziantep, Turkey; 2Department of Biostatistics, School of Medicine, Gaziantep University, Gaziantep, Turkey Purpose: The number of patients who make it to receive third-line chemotherapy is increasing owing to the improvements in adverse-event management of chemotherapy for small-cell lung cancer (SCLC). Sequencing of optimal treatment for SCLC is still a challenge for oncologists. In this paper, we aim to present a different approach to the treatment of SCLC.Methods: Between January 2008 and July 2014, all patients diagnosed with extensive-stage SCLC and treated with third-line chemotherapy at Gaziantep University Oncology Hospital were analyzed retrospectively. Disease control rates and progression-free survival (PFS) for first-, second-, and third-line chemotherapy, and overall survival (OS) were recorded. Survival analysis was calculated by using Kaplan–Meier method.Results: A total of 255 SCLC patients were screened, and 25 of those patients who received third-line chemotherapy were included in this study. Median age was 57±10.131 years (range:39–74 years). Disease control rates at first-, second-, and third-line chemotherapy were 92%, 68%, and 44%, respectively. Fourteen patients received irinotecan followed by topotecan, and eleven patients received topotecan followed by irinotecan. Second-line median PFS was statistically better in patients treated with irinotecan at second-line compared with those treated with topotecan (21 vs 12 weeks, P=0.018). Comparison of third-line median PFS of the two groups was not statistically significant (14 vs 12 weeks, P=0.986). Median OS was not statistically significant in patients who received irinotecan followed by topotecan vs those who received topotecan followed by irinotecan (18 vs 14 months, P=0.112).Conclusion: Sequential monotherapy with topotecan and irinotecan provides a considerable contribution to OS, and second-line irinotecan showed a better PFS, despite a similar OS, compared with topotecan. Keywords: small-cell lung cancer, irinotecan, topotecan, third-line chemotherapy

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±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 12months 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 3months were 73.1%, 35.3%, and 41.2% (P=0.026, odds ratio [OR]=4.39; 95% confidence interval [CI]: 1.45–13.26), respectively. The PFS rates of EGFR positive, negative, and unknown patients for 6months were 50%, 29.4%, and 29.4% (P=0.267, OR: 2.4; 95% CI: 0.82–6.96), respectively. The PFS rates of EGFR positive, negative, and unknown patients for 12months were 42.3%, 29.4%, 23.5% (P=0.408, OR: 2.0; 95% CI: 0.42–5.26), respectively. Thirty-one of 60 patients had SUVmax values ≤11. The PFS rates for 3, 6, and 12months were 70.5%/28% (P=0.001, OR=9.0; 95% CI: 2.79–29.04), 61.7%/8% (P11) 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, prognosis

Tulay Kus, Gokmen Aktas, Alper Sevinc, Mehmet Emin Kalender, Celaletdin Camci Department of Internal Medicine, Division of Medical Oncology, Gaziantep University, Gaziantep, Turkey Abstract: Erlotinib, an epidermal growth factor receptor and tyrosine kinase inhibitor, is a targeted drug that was approved for the treatment of non-small-cell lung cancers and pancreatic cancers. Targeted tyrosine kinase inhibitors are known to have cardiotoxic effects. However, erlotinib does not have a statistically proven effect of increasing acute cardiovascular event (ACE) risk. Preclinical studies showed that beta agonist stimulation among rats that were administered erlotinib led to cardiovascular damage. Thus, there would be an aggregate effect of erlotinib on ACE, although it is not thought to be a cardiotoxic drug itself. In this paper, we present two non-small-cell lung cancer cases that developed ACE under erlotinib treatment. Keywords: erlotinib, lung cancer, myocardial infarction, EGFR

Background/Aims: This study aimed to determine the epidemiological characteristics of colorectal cancer in Turkey. Materials and Methods: In this multicenter, prospective, and cross-sectional registry study, data for 968 patients with colorectal cancer from 21 centers in 7 geographic regions were analyzed. Results: Diagnosis was colon cancer in 662 (68.4%) and rectum cancer in 306 (31.6%) patients. In total, 60.9% of patients was male; mean age was 58.9 +/- 12.6 years. Among patients, 15.0% was drinking alcohol, 17.5% was smoking, 1.5% had familial history of polyposis, 15.0% had diabetes mellitus, 1.0% had inflammatory bowel disease. Fruit and vegetable consumption was low (= 3 times/week) in 47.4% of the patients. Median time-to diagnosis was 3.0 months and 4.0 months for patients with colon and rectum cancer, respectively. Mean body mass index was >25 in all group of patients. Distal rectum (61.3%) and sigmoid colon (36.8%) were the most common locations of cancer, for rectum and colon respectively. In total, 85.6% of patients were operated; 25.8% had emergency surgery. Low anterior resection rate was 64.2% in rectum cancer. In majority (89.8%) of the patients with rectum cancer who received preoperative treatment, conventional chemo-radiotherapy regimen was given. pTNM staging at diagnosis showed that stage III and IV patients were in majority (35.9% and 29.7%, respectively). Conclusion: Colon cancer is more frequent than rectum cancer in Turkey. Colorectal cancer patients are diagnosed at later stages. Most of the cases were operated. Interregional differences for risk factors are worthwhile for evaluation in future trials.

Background: We tried to understand whether or not there is an association between higher prevalence of smoking and autosplenectomy in sickle cell diseases (SCDs) cases. Methods: All SCDs patients with and without autosplenectomy were studied, and they were compared in between. Results: The study included 253 patients (124 females). There were 168 cases (66.4%) with autosplenectomy and 85 cases (33.5%) without (p0.05). Thalassemia minors were significantly higher in cases without autosplenectomy (91.7% versus 50.0%, p0.05 for both). Both the white blood cell and platelet counts of the peripheric blood were higher in cases with autosplenectomy, significantly (p = 0.000 for both), whereas the mean hematocrit value was significantly lower in them (p= 0.000). On the other hand, prevalences of digital clubbing, pulmonary hypertension, leg ulcers, chronic renal disease, coronary heart disease, and rheumatic heart disease were significantly higher in cases with autosplenectomy (p

Kula, Levent/0000-0002-8208-9728 WOS: 000300921900005 In this paper, we give some characterizations of position vector of a unit speed curve in a regular surface M subset of E-3 which always lies in the planes spanned by {T, Z}, {T, Y} and {Y, Z}, respectively, by using (curve-surface)-frame {T,Y,Z} instead of Frenet frame {T, N, B}. We characterize such curves in terms of the geodesic curvature k(g), normal curvature k(n) and geodesic torsion t(r). Furthermore, we give some characterization for the regular surface M by using the concept of transversality of surfaces in Euclidean 3-space.

WOS: 000231641500010 PubMed: 16115177 Gastric cancer (GCa) is still a common cause of cancer-related deaths worldwide, despite improved diagnostic and therapeutic implications. Hence, early diagnosis has critical importance. Flow cytometry reveals rapid and reproducible quantification of nuclear DNA content of disaggregated tissues and assessment of its significance in various malignant and precancerous lesions. A total of 121 patients with GCa, chronic atrophic gastritis (CAG), gastric polyps, intestinal metaplasia (IM) and gastric dysplasia and 36 healthy controls were enrolled in this study. Flow cytometric measurements of DNA ploidy, total S-Phase, G(2)M-phase and proliferative indexes (PIs) were analysed on fresh gastric biopsy specimens obtained by gastroscopy. DNA aneuploidy was present in 43.75% of the GCas (p < 0.05). We found a DNA aneuploidy rate of 15.38% in CAG, 15.38% in IM and 25% in epithelial dysplasia. One of nine polyps had aneuploidy. None of the normal gastric mucosa samples showed aneuploidy. The controls had lower rates of total S-phase and PIs (p < 0.05). In conclusion, DNA flow cytometry may be offered as an objective diagnostic tool for earls detection of malignant transformation in gastric lesions.

This report describes the first Turkish family to be diagnosed with Bernard-Soulier syndrome. The family consists of nine members (two parents, three sons and four daughters). The parents were first cousins. The index case, a 22 year-old-man, had a history of haemorrhagic diathesis with thrombocytopenia, giant platelets in the peripheral blood smear and a prolonged bleeding time. Refractory idiopathic thrombocytopenic purpura had been diagnosed elsewhere and a splenectomy had been performed six months previously. Ristocetin agglutination of platelets was defective and flow cytometry analysis of platelet membrane glycoprotein showed markedly reduced expression of glycoprotein lb (2.1%). Bernard-Soulier syndrome was diagnosed. Increased mean platelet volume was found in both parents, one son and three daughters. The other son and daughter were normal.

The objective of this study was to assess the toxicity and efficacy of high-dose chemotherapy (HDC) with autologous peripheral stem cell transplantation (APBSCT) in women with metastatic or high risk (?9 axillary nodal involvement) stage II-III breast cancer. Forty-five women with either metastatic (n=23) or high risk (n=22) breast cancer were enrolled in the study and treated with HDC followed by APBSCT. At the time of transplant, the median age was 39 years (range: 26-64). All patients were pretreated with standard chemotherapy regimens. Metastatic patients with progression or stable disease after first-line chemotherapy were excluded. PBSC were harvested using G-CSF and the conditioning regimens ICE (ifosfamide, carboplatin, etoposide) and CNV (cyclophosphamide, mitoxantrone, etoposide) were used in most of the patients. The median number of CD34+ cells infused was 5.40×106/kg (range: 1.82-19.87×106 kg). G-CSF or GM-CSF was used in 39 patients in the post-transplant period. The median leukocyte engraftment (leukocyte

Blastocystis hominis has been considered as a harmless parasite, but there are many authors who consider this organism as an intestinal pathogen especially in immunocompromised patients. In this report, the stool samples from a patient with acute nonlymphoblastic leukemia who had recurrent diarrhea were examined. The samples were examined before and after formaline ether concentration, iodine, Gram, modified Ziehl-Neelsen and trichrome permanent stained smears and also cultured for bacterial pathogens. Rotavirus was also screened by a latex agglutination assay. B. hominis was detected in stool samples. This report states that B. hominis may be a cause of intestinal pathogen especially in immunocompromised patients and should be sought in feces when gastrointestinal symptoms are present.