What is the Mechanism of Progression with Trastuzumab Treatment - Escape or Resistance?

Sendur, Mehmet Ali Nahit,Aksoy, Sercan,Ozdemir, Nuriye Yildirim,Zengin, Nurullah,Altundag, Kadri Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

Human epidermal growth factor receptor (HER) 2 overexpression, observed in 20-25 percent of invasive breast cancers, is well known to be associated with a more aggressive phenotype and poor prognosis, with resistance to certain chemotherapeutic agents. The majority of patients with metastatic breast cancer who initially respond to trastuzumab, demonstrate disease progression within 1 year of treatment initiation. Furthermore, lack of response in some patients and relapse during the course of therapy, continue to challenge researchers and clinicians. A better understanding of the fundamental mechanisms of trastuzumab action is required so that new therapies directed at HER2 can be developed. We present here findings for mechanisms, both of Trastuzumab action and clinical resistance or escape.

Does Zoledronic Acid Have Additive Effect on Suppression of Plasma Estrogen Levels ?

Sendur, Mehmet Ali Nahit,Aksoy, Sercan,Ozdemir, Nuriye Yildirim,Akinci, Muhammed Bulent,Zengin, Nurullah,Altundag, Kadri Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

Optimization of Aniline Biopolymerization Reaction Conditions By Response Surface Methodology (RSM)

Adnan Aldemir,Emre Birhanlı,Nahit Aktaş,Özfer Yeşilada 보안공학연구지원센터 2014 International Journal of Bio-Science and Bio-Techn Vol.6 No.6

Response Surface Methodology(RSM) was applied to enzymatic polymerization of aniline, which was conducted in a closed system containing sodium acetate buffer and presence of poly(sodium 4-styrene sulfonate)(SPS) polyelectrolyte as a template with laccase enzyme to produce water soluble polyaniline. Laccase enzyme used as catalyst was isolated from Trametes versicolor (ATCC 200801). The enzymatic polymerization rate of aniline based on measurements of initial dissolved oxygen (DO) consumption rate in the closed system, was optimized by the application of RSM. The independent variables, which had been found the most effective variables on the initial DO consumption rate by screening experiments, were determined as monomer concentration, medium temperature and medium pH. A quadratic model was developed through RSM in terms of related independent variables to describe the initial DO consumption rate as the response. Based on statistic analysis, optimum reaction conditions for the maximum initial DO consumption rate determined 42.50 mM, 39.34 °C and 5.45 as monomer concentration, medium temperature and medium pH, respectively.

A trilinear stress-strain model for confined concrete

Toshibumi Fukuta,Alper Iiki,Nahit Kumbasar,Pinar Ozdemir 국제구조공학회 2004 Structural Engineering and Mechanics, An Int'l Jou Vol.18 No.5

A trilinear stress-strain model for confined concrete

Ilki, Alper,Kumbasar, Nahit,Ozdemir, Pinar,Fukuta, Toshibumi Techno-Press 2004 Structural Engineering and Mechanics, An Int'l Jou Vol.18 No.5

For reaching large inelastic deformations without a substantial loss in strength, the potential plastic hinge regions of the reinforced concrete structural members should be confined by adequate transverse reinforcement. Therefore, simple and realistic representation of confined concrete behaviour is needed for inelastic analysis of reinforced concrete structures. In this study, a trilinear stress-strain model is proposed for the axial behaviour of confined concrete. The model is based on experimental work that was carried out on nearly full size specimens. During the interpretation of experimental data, the buckling and strain hardening of the longitudinal reinforcement are also taken into account. The proposed model is used for predicting the stress-strain relationships of confined concrete specimens tested by other researchers. Although the proposed model is simpler than most of the available models, the comparisons between the predicted results and experimental data indicate that it can represent the stress-strain relationship of confined concrete quite realistically.

Low strength concrete members externally confined with FRP sheets

Ilki, Alper,Kumbasar, Nahit,Koc, Volkan Techno-Press 2004 Structural Engineering and Mechanics, An Int'l Jou Vol.18 No.2

In this paper axial loading tests on low strength concrete members, which were confined with various thickness of carbon fiber reinforced polymer (CFRP) composite sheets are described. Totally 46 specimens with circular, square and rectangular cross-sections with unconfined concrete compressive strengths between 6 and 10 MPa were included in the test program. During the tests, a photogrammetrical deformation measurement technique was also used, as well as conventional measurement techniques. The contribution of external confinement with CFRP composite sheets to the compressive behavior of the specimens with low strength concrete is evaluated quantitatively, in terms of strength, longitudinal and lateral deformability and energy dissipation. The effects of width/depth ratios and the corner radius of the specimens with rectangular cross-section on the axial behavior were also examined. It was seen that the effectiveness of the external confinement with CFRP composite sheets is much more pronounced, when the unconfined concrete compressive strength is relatively lower. It was also found that the available analytical expressions proposed for normal or high strength concrete confined by CFRP sheets could not predict the strength and deformability of CFRP confined low strength concrete accurately. New expressions are proposed for the compressive strength and the ultimate axial strain of CFRP confined low strength concrete.

Behavior of damaged and undamaged concrete strengthened by carbon fiber composite sheets

Ilki, Alper,Kumbasar, Nahit Techno-Press 2002 Structural Engineering and Mechanics, An Int'l Jou Vol.13 No.1

Many existing concrete structures suffer from low quality of concrete and inadequate confinement reinforcement. These deficiencies cause low strength and ductility. Wrapping concrete by carbon fiber reinforced polymer (CFRP) composite sheets enhances compressive strength and deformability. In this study, the effects of the thickness of the CFRP composite wraps on the behavior of concrete are investigated experimentally. Both monotonic and repeated compressive loads are considered during the tests, which are carried out on strengthened undamaged specimens, as well as the specimens, which were tested and damaged priorly and strengthened after repairing. The experimental data shows that, external confinement of concrete by CFRP composite sheets improves both compressive strength and deformability of concrete significantly as a function of the thickness of the CFRP composite wraps around concrete. Empirical equations are also proposed for compressive strength and ultimate axial deformation of FRP composite wrapped concrete. Test results available in the literature, as well as the experimental results presented in this paper, are compared with the analytical results predicted by the proposed equations.

Evaluation of Renal Function Using the Level of Neutrophil Gelatinase-Associated Lipocalin is Not Predictive of Nephrotoxicity Associated with Cisplatin-Based Chemotherapy

Kos, F. Tugba,Sendur, Mehmet Ali Nahit,Aksoy, Sercan,Celik, Huseyin Tugrul,Sezer, Sevilay,Civelek, Burak,Yaman, Sebnem,Zengin, Nurullah Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.2

Background: For early detection of renal damage during the usage of cisplatin based chemotherapy, changes in renal function should be monitored carefully. In recent years, neutrophil gelatinase-associated lipocalin, a small polypeptide molecule, has shown promise as a marker of acute renal failure. The aim of this present study was to assess possible risk prediction of cisplatin-induced nephrotoxicity using serum NGAL. Materials and Methods: A total of 34 consecutive patients with documented serum creatinine at least 24 hours before every cycle of cisplatin-based chemotherapy were included in the study. Demographic and medical data including age, performance status, tumor characteristics and comorbid diseases were collected from medical charts. Renal function was evaluated at least 48 hours before the treatment and at the end of the treatment based on the Modification of Diet in Renal Disease (MDRD) formula. Before and after cisplatin infusion serum NGAL levels were measured for the first and 3rd cycles of chemotherapy. Results: The median age of the study population was 54 (32-70) years. Fifteen patients (41.1%) were treated on an adjuvant basis, whereas 19 patients (58.9%) were treated for metastatic disease. There was no correlation of serum NGAL levels with serum creatinine (r=0.20, p=0.26) and MDRD (r=-0.12, p=0.50) and creatinine clearance-Cockcroft-Gault (r=-0.22, p=0.22) after cisplatin infusion at the end of the 3rd cycle of chemotherapy. Conclusions: In our study, serum NGAL levels were not correlated with the cisplatin induced nephrotoxicity. Further prospective studies are needed to conclude that serum NGAL level is not a good surrogate marker to predict early cisplatin induced nephrotoxicity.

Serum 25-hydroxy Vitamin D Status is Not Related to Osteopenia/Osteoporosis Risk in Colorectal Cancer Survivors

Akinci, Muhammed Bulent,Sendur, Mehmet Ali Nahit,Aksoy, Sercan,Yazici, Ozan,Ozdemir, Nuriye Yildirim,Kos, Tugba,Yaman, Sebnem,Altundag, Kadri,Zengin, Nurullah Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8

Background: The incidence of colorectal cancer increases with vitamin D deficiency as shown in recently published studies. In addition, prospective investigations have indicated that low vitamin D levels may be associated with increased mortality of colorectal cancer, especially in stage III and IV cases. However, the exact incidence of vitamin D deficiency and the relation between vitamin D deficiency and osteopenia/osteporosis is still not known. The aim of this study is to identify severity of vitamin D deficiency and absolute risk factors of osteopenia/osteoporosis in colorectal cancer survivors. Materials and Methods: A total of 113 colorectal cancer survivors treated with surgery and/or chemotherapy ${\pm}$ radiotherapy were recruited from medical oncology outpatient clinics during routine follow-up visits in 2012-2013. Bone mineral densitometry (BMD) was performed, and serum 25-OH vitamin D levels were also checked on the same day of the questionnaire. The patients was divided into 2 groups, group A with normal BMD and group B with osteopenia/osteoporosis. Results: The median age of the study population was 58 (40-76). Thirty (30.0%) were female, whereas 79 (70.0%) were male. The median follow-up was 48 months (14-120 months). Vitamin D deficiency was found in 109 (96.5%); mild deficiency (20-30 ng/ml) in 19 (16.8%), moderate deficiency (10-20 ng/ml) in 54 (47.8%) and severe deficiency (<10 ng/ml) in 36 (31.9%). Osteopenia was evident in 58 (51.4%) patients whereas osteoporosis was noted in 17 (15.0%). Normal BMD was observed in 38 (33.6%). No apparent effects of type of surgery, presence of stoma, chemotherapy, radiotherapy and TNM stage were found regarding the risk of osteopenia and osteoporosis. Also, the severity of the vitamin D deficiency had no effect in the risk of osteopenia and osteporosis (p=0.93). In female patients, osteopenia/osteoporosis were observed in 79.5% patients as compared to 60.7% of male patients (p=0.04). Conclusions: In our study, vitamin D deficiency and osteopenia/osteoporosis was observed in 96.5% and 66.4% of colorectal cancer survivors, respectively. There is no defined absolute risk factor of osteopenia and osteoporosis in colorectal cancer survivors. To our knowledge, in the literature, our study is the first to evaluateall the risk factors of osteopenia and osteoporosis in colorectal cancer survivors.

Efficacy and Safety of First Line Vincristine with Doxorubicin, Bleomycin and Dacarbazine (ABOD) for Hodgkin's Lymphoma: a Single Institute Experience

Ozdemir, Nuriye,Dogan, Mutlu,Sendur, Mehmet Ali Nahit,Yazici, Ozan,Abali, Huseyin,Yazilitas, Dogan,Akinci, Muhammed Bulent,Aksoy, Sercan,Zengi, Nurullah Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

Background: ABVD (doxorubicin, bleomycin, vinblastine (Vb) and dacarbazine) is the standard regimen in Hodgkin's lymphoma (HL).Vincristine (O) is a mitotic spindle agent like Vb. We aimed to evaluate the efficacy and safety of O as a part of ABOD in HL. Materials and Methods: Patients who had ABOD were enrolled. Stage I-II HL were evaluated for unfavorable risk factors according to NCCN. National Cancer Institute Common Toxicity Criteria was used for toxicity. Results: Seventy-nine HL patients in our center between 2003 and 2007 were evaluated retrospectively. Median follow-up was 54 months. Most of the patients were male in their third decade. Median ABOD cycles were 6 (2-8). Primary refractory disease rate was 17.7% whereas it was 5.1% for early relapse and 5.1% for late relapse disease. Response rates were as 82.3% for complete response, 11.4% for partial response, 5.1% for stable disease and 1.3% for progressive disease. Half of relapsed patients had autologous stem cell transplantation. Estimated 5-year failure-free survival was 71% and significantly longer in early stage patients without risk factors, bulky disease or radiotherapy (RT) (p=0.05, p<0.0001, p=0.02; respectively). Estimated 5-year overall survival was 74% and significantly longer in those who had no RT (p=0.001). Dose modification rate was 5.1% and chemotherapy delay rate was 19%. There were no toxicity-related deaths. Conclusions: ABOD seems to be effective with managable toxicity in HL, even in those with poor prognostic factors.