The effect of CYP1A2 gene polymorphisms on Theophylline metabolism and chronic obstructive pulmonary disease in Turkish patients

( Ahmet Uslu ),( Candan Ogus ),( Tulay Ozdemir ),( Turker Bilgen ),( Ozgur Tosun ),( Ibrahim Keser ) 생화학분자생물학회 (구 한국생화학분자생물학회) 2010 BMB Reports Vol.43 No.8

Cytochrome P450 (CYP) 1A2 gene polymorphisms are thought to be involved in the metabolism of theophylline (TP). We aimed to investigate the effect of CYP1A2*1C, CYP1A2*1D, CYP1A2*1E, and CYP1A2*1F polymorphisms of the CYP1A2 on TP metabolism by PCR-RFLP in 100 Turkish patients with chronic obstructive pulmonary disease (COPD) receiving TP. One hundred and one healthy volunteers were included as control group. The genotype frequencies of the CYP1A2*1D and CYP1A2*1F were found to be significantly different in the patients compared to the controls. The “T” allele at -2467 delT and the “C” allele at -163 C > A in the CYP1A2 displayed association with a significantly increased risk for COPD. “T” allele at -2467 delT was also associated with a high risk of disease severity in COPD. In conclusion, our data suggest that genetic alterations in CYP1A2 may play a role both in the pharmacogenetics of TP and in the development of COPD. [BMB reports 2010; 43(8): 530-534]

Electrical and Dielectric Properties and Intersection Behavior of G/!-V Plots for Al/Co-PVA/p-Si (MPS) Structures at Temperatures below Room Temperature

Ibrahim Yucedag,Ahmet Kaya,Semsettin Altindal,Ibrahim Uslu 한국물리학회 2014 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.65 No.12

Both the electrical and the dielectric properties of the Al/Co-doped polyvinyl alcohol/p-Simetal-polymer-semiconductor (MPS) structure have been studied using temperature-dependentadmittance-voltage (C/G-V) measurements at temperatures below room temperature at 300 kHz. The C-V plot indicates two peaks for each temperature corresponding to inversion and accumulationregions, respectively. The first peak was attributed to a particular distribution of interfacetraps (Dit), and the second was attributed to the series resistance (Rs) and interfacial polymerlayer. G/!-V plots show almost U-shape behavior for all temperatures and a crossing at almost 3V. Such behavior of the G/!-V plots may be attributed to the lack of free charge at low temperatures. After this intersection point, while the value of the capacitance (C) starts decreasing, theG/! continues to increase. The temperature-dependent real and imaginary parts of the dielectricconstant ("0, "00) and of the electric modulus (M0, M00), as well as the ac electrical conductivity(ac), of structure were obtained using C and G data before and after the intersection point (at2 and 6 V), respectively. Experimental results show that the "0, "00, loss tangent (tan), ac, M0,and M00 values were strong functions of the temperature and the applied bias voltage. In addition,G/!-T and "00-T plots show two different behaviors, one before and the other after the intersectionpoint.

First-Line Mono-Chemotherapy in Frail Elderly Patients with Metastatic Colorectal Cancer

Varol, Umut,Dirican, Ahmet,Yildiz, Ibrahim,Oktay, Esin,Degirmenci, Mustafa,Alacacioglu, Ahmet,Barutca, Sabri,Karabulut, Bulent,Uslu, Ruchan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Background: Unlike for fit elderly metastatic colorectal cancer (mCRC) patients, general approaches to initial treatment for the frail older mCRC patients are not clear. Our aim was to evaluate the efficiency and safety of first-line single-agent treatment in one such group. Materials and Methods: We retrospectively evaluated mCRC patients aged 70 or older with an Eastern Cooperative Oncology Group performance score of 2. They had no prior treatment and underwent first-line single-agent capecitabine or other monotherapies until disease progression or unacceptable toxicity. Results: Thirty-six patients were included. Most (n:28, 77.8%) were treated with capecitabine. One patient achieved a complete response and 5 patients had a partial response for an overall response rate of 16.6%. Twelve patients (33.3%) remained stable. Median progression free survival was 5 months (confidence interval (CI), %; 3.59-6.40) and median overall survival was 10 months (95 CI%; 8.1-11.8). Grade 3-4 toxicity was found in 6 patients (16.6%). Febrile neutropenia was not observed and there were no toxicity-associated deaths. Conclusions: Capecitabine is a safe chemotherapeutic agent with moderate activity for first-line treatment of older metastatic colorectal cancer patients with limited performance status.

Fabrication and characterization of bismuth oxideeholmia nanofibers and nanoceramics

Arda Aytimur,Serhat Koçyigit,Ibrahim Uslu,Senol Durmusoglu,Ahmet Akdemir 한국물리학회 2013 Current Applied Physics Vol.13 No.3

In this article, a novel and simple method to produce both boron doped and undoped holmia stabilized bismuth oxide nanoceramic materials has been put forward. Boron doped and undoped poly (vinyl alcohol)/bismutheholmia acetate nanofibers were produced using the electrospinning technique and were calcined at 850 C afterward in order to obtain nanopowder. The characteristics of the nanofibers were investigated with FT-IR, XRD, and SEM. XRD analyses showed that boron undoped holmia stabilized bismuth oxide nanopowders have the face-centered cubic structure (d-phase), and that the incorporation of boron atoms into the composite prevents the nucleus formation and turns the structure into a more amorphous glassy form. The SEM micrographs of the fibers showed that the addition of boron results in the formation of cross-linked bright-surfaced fibers. The average fiber diameters for electrospun boron doped and undoped PVA/BieHo acetate nanofibers were calculated using the ImageJ software as 102 nm and 171 nm, respectively.

Anticancer Therapy for Breast Cancer Patients with Skin Metastases Refractory to Conventional Treatments

Varol, Umut,Yildiz, Ibrahim,Alacacioglu, Ahmet,Uslu, Ruchan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

Skin metastases of breast cancer are usually late events in the course of tumor progression and signify a poor prognosis. They may remain as a therapeutic challenge especially after failure of standard treatments. Topical interventions, together with or without radiotherapy, may only palliate the symptoms temporarily. However, there may be alternative treatment modalities for unresectable breast cancer skin metastases resistant to chemotherapy and radiotherapy. There are various genetic alterations in tumors and therapeutic potential of expression patterns for factors like epidermal growth factor receptor may have important clinical implications in case of disease refractory to the conventional treatments. Here, we clarified the therapeutic options and genetic alterations in skin metastatic breast cancer patients refractory to standard chemotherapeutics.

Poster Session:PS 0481 ; Nephrology : Analgesic Nephropathy Associated with Total Anuria

( Yaloin Onem ),( Ali Kutlu ),( Seyit Ahmet Uslu ),( Barbaros Basbug ),( Muslum Sagir ),( Yusuf Hazcerli ),( Mustafa Hatipoglu ),( Kemal Kara ),( Ramazan Arikan ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Introduction and Aim:While ischemia and nefrotoxins account for almost 45 % of all acute renal failure cases, prerenal (caused by congestive cardiac failure, liquid insuffi - ciency, sepsis and medication) azotemia accounts for around 20%. Among nefrotoxins, nonstereoid anti-infiammatory drugs (NSAII) may affect kidneys through multiple mechanisms (causing hemodynamic, acute allergic interstitial nephritis, papillary necrosis or glomerular nephritis). Herein, we present a patient who developed analgesic nephropathy associated with total anuria. Case: A patient with a medical history of benign prostatic hyperplasia, coronary artery disease, hypertension and tuberculosis was admitted to our department of emergency with complaints of dyspnea and headache. Laboratory examination revealed the following Results: urea: 138 mg/dL, kreatinin: 5,20 mg/dL, BK: 19300, ALT: 319 U/L AST: 324 U/ L LDH: 1947 U/L. The patient was diagnosed with total anuria. Because the patient had a history of analgesic usage, he was scheduled to undergo hemodialysis 3 times per week with a prediagnosis of analgesic nephropathy. Although initially renal function tests demonstrated a slight deterioration (urea: 177 mg/dL and creatinine: 8 mg/dL) they displayed a gradual decrease following ongoing hemodialysis sessions and consequently returned to normal (urea: 48 mg/dL and creatinine: 1, 25 mg/dL). The patient also received piperacillin/tazobactam 3x 2, 25 gr/day due to a concern for aspiration pneumonia. Diagnostic bronchoscopy results were in compliance with fi brosis at microscopic level. Conclusion/Recommendations: Analgesic nefropathy should be investigated when inquiring for the etiology of acute renal failure. Patients with total anuria should receive comprehensive treatment comprising renal replacement therapy such as hemodialysis. Additionally, interstitial lung disease and overlapping aspiration pneumonia may complicate the condition. Therefore, they also should be considered. Even patients with total anuria may return to normal life following a comprehensive and rigorous approach.

Second-Line Capecitabine and Oxaliplatin Combination for Gemcitabine-Resistant Advanced Pancreatic Cancer

Bayoglu, Ibrahim Vedat,Varol, Umut,Yildiz, Ibrahim,Muslu, Ugur,Alacacioglu, Ahmet,Kucukzeybek, Yuksel,Akyol, Murat,Demir, Lutfiye,Dirican, Ahmet,Cokmert, Suna,Yildiz, Yasar,Karabulut, Bulent,Uslu, Ruc Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17

Background: The role of second-line therapy in metastatic pancreatic cancer is not clear. In this study, we aimed to explore the second-line efficiency of capecitabine and oxaliplatin (XELOX) in patients with advanced pancreatic cancer who have received gemcitabine-based first-line therapy. Materials and Methods: We retrospectively evaluated 47 patients with locally advanced or metastatic pancreatic cancer previously treated with gemcitabine-based first-line regimens. Treatment consisted of oxaliplatin $130mg/m^2$ and capecitabine $1000mg/m^2$ twice daily with a 3 week interval, until unacceptable toxicity or disease progression. Results: Median number of cycles was 4 (range, 2-10). The overall disease control rate was 38.3%. The median overall survival and progression-free survival from the start of second-line therapy were 23 weeks (95%CI: 16.6-29.5 weeks) and 12 weeks (95%CI: 9.8-14.4 weeks), respectively. The most common grade 3-4 toxicities were nausea, vomiting and hematologic side effects. Conclusions: Our result suggests that the combination of capecitabine and oxaliplatin was tolerated with manageable toxicity and showed encouraging activity as second-line treatment of advanced or metastatic pancreatic cancer patients with ECOG performance status 0-2.

Role of PET/CT in Treatment Planning for Head and Neck Cancer Patients Undergoing Definitive Radiotherapy

Arslan, Sonay,Abakay, Candan Demiroz,Sen, Feyza,Altay, Ali,Akpinar, Tayyar,Ekinci, Ahmet Siyar,Esbah, Onur,Uslu, Nuri,Kekilli, Kezban Esra,Ozkan, Lutfi Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Background: In this study, we aimed to investigate the benefits of 18F-deoxyglucose positron emission tomography/computed tomography (FGD-PET/CT) imaging for staging and radiotherapy planning in patients with head and neck cancer undergoing definitive radiotherapy. Materials and Methods: Thirty-seven head and neck cancer patients who had undergone definitive radiotherapy and PET/CT at the Uludag University Medical Faculty Department of Radiation Oncology were investigated in order to determine the role of PET/CT in staging and radiotherapy planning. Results: The median age of this patient group of 32 males and 5 females was 57 years (13-84years). The stage remained the same in 18 cases, decreased in 5 cases and increased in 14 cases with PET/CT imaging. Total gross tumor volume (GTV) determined by CT (GTVCT-Total) was increased in 32 cases (86.5%) when compared to total GTV determined by PET/CT (GTVPET/CT-Total). The GTV of the primary tumor determined by PET/CT (GTVPET/CT) was larger in 3 cases and smaller in 34 cases compared to that determined by CT (GTVCT). The GTV of lymph nodes determined by PET/CT (GTVLNPET/CT) was larger in 20 cases (54%) and smaller in 12 cases (32.5%) when compared to GTV values determined by CT (GTVLNCT). No pathological lymph nodes were observed in the remaining five cases with both CT and PET/CT. Conclusions: We can conclude that PET/CT can significantly affect both pretreatment staging and assessed target tumor volume in patients with head and neck cancer. We therefore recommend examining such cases with PEC/CT before treatment.

Hepatitis B and C Seroprevalence in Solid Tumors - Necessity for Screening During Chemotherapy

Oguz, Arzu,Aykas, Fatma,Unal, Dilek,Karahan, Samet,Uslu, Emine,Basak, Mustafa,Karaman, Ahmet Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.3

Background: Hepatitis B and C are the leading causes of liver diseases worldwide. For hematological and solid malignancy patients undergoing chemotherapy, increases in HBV DNA and HCV RNA levels can be detected which may result in reactivation and hepatitis-related morbidity and mortality. The aim of this study was to determine the seroprevalence of Hbs ag and Anti HCV positivity in patients with solid malignancies undergoing chemotherapy and consequences during follow-up. Materials and Methods: The files of 914 patients with solid malignancies whose hepatitis markers were determined serologically at diagnosis were reviewed retrospectively. All underwent adjuvant/palliative chemotherapy. For the cases with HBV and/or HCV positivity, HBV DNA and HCV RNA levels, liver function tests at diagnosis and during follow-up and the treatment modalities that were chosen were determined. Results: Of 914 cases, Hbs Ag, anti Hbs and anti HCV positivity were detected in 40 (4.4%), 336 (36.8%) and 26 (2.8%) of the cases respectively. All of the Hbs ag positive patients received prophylactic lamuvidine before the start of chemotherapy. In the Hbs ag and anti HCV positive cases, liver failure was not detected during chemotherapy and a delay in chemotherapy courses because of hepatitis was not encountered. Conclusions: Just as with hematological malignancies, screening for HBV and HCV should also be considered for patients with solid tumors undergoing chemotherapy. Prophylactic antiviral therapy for HBV reduces both the reactivation rates and HBV related mortality and morbidity. The clinical impact of HCV infection on patients undergoing chemotherapy is still not well characterized.

Effects of EGFR, CK19, CK20 and Survinin Gene Expression on Radiotherapy Results in Patients with Locally Advanced Head and Neck Cancer

Kekilli, Kezban Esra,Abakay, Candan Demioz,Tezcan, Gulcin,Tunca, Berrin,Egeli, Unal,Saraydaroglu, Ozlem,Esbah, Onur,Ekinci, Ahmet Siyar,Arslan, Sonay,Uslu, Nuri,Ozkan, Lutfi Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

Purpose: To investigate the effects of epidermal growth factor receptor (EGFR), cytokeratin 19 (CK19), cytokeratin 20 (CK20) and survinin gene expression on local control (LC) and overall survival (OS) in patients with locally advanced head and neck cancer (LAHNC) who were administered radiotherapy (RT). Materials and Methods: Twenty-six patients who were admitted to Uludag University Medical Faculty Department of Radiation Oncology with a diagnosis of LAHNC (GIII-GIV) were included in this study. Gene expression was evaluated in tumor tissues and peripheral blood. RNA isolation was performed on paraffinized tumor tissues and peripheral blood samples obtained before RT (BR). The densities of the obtained RNAs were analyzed at 260/280 nm. cDNA samples obtained from total RNA,EGFR, CK19, CK20 and survinin gene expression levels were assessed via the Sybr Green method and data were analyzed with the ${\Delta}{\Delta}Ct$ method. The same process was repeated for peripheral blood samples taken after RT (AR). Results: The female/male ratio was 3:23 and the mean age was 56.5 years (38-75years). After radiotherapy, CK19 and CK20 levels in the peripheral blood were found to be correlated according to Pearson correlation analysis(p=0.049). This result indicates a possibility of remaining positive for CK19 and CK20 in the peripheral blood even after RT in patients with CK19, CK20, and EGFR positive tumors before RT. There was a statistically significant correlation between survinin levels measured BR and AR (p=0.028). Conclusions: In this study, we found that patients with any EGFR, CK19, CK20 or survinin positivity in their peripheral blood obtain less benefit from radiotherapy. A wider patient population and advanced protein analyses are necessary in order to increase the reliability of our findings.