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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.
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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
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Yazilitas, Dogan,Sendur, Mehmet Ali Nahit,Karaca, Halit,Ozdemir, Nuriye,Aksoy, Sercan,Berk, Veli,Yazici, Ozan,Ozturk, Banu,Ozkan, Metin,Zengin, Nurullah,Altundag, Kadri Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.4
Background: Adding taxanes to adjuvant antracycline and cyclophosphamide (AC) in combination may provide significant improvement in node-positive and high risk node-negative breast cancer (BC) patients. However, the optimal dose and the role of dose-dense (DD) chemotherapy have yet to be determined. The aim of this study was to compare the efficacy of a DD paclitaxel (P)-AC combination with conventional weekly P-AC or docetaxel D-AC combinations in patients with node-positive breast cancer. Materials and Methods: Newly diagnosed 280 node-positive BC patients diagnosed from 1998 to 2013 in three clinics were retrospectively analyzed. Demographic and medical data were collected from the medical charts. Patients were categorized to 3 groups according to treatment arms: arm A, ddAC-P; arm B, weekly P and AC combination; and arm C; T and AC combination. Adjuvant trastuzumab was added for HER2-positive patients. Kaplan-Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). The log-rank test was used to examine the statistical significance of the differences observed between the groups. Two-sided P values <0.05 were considered statistically significant. Results: Of the total of 280 patients, 101 were in arm A, 114 in arm B and 65 in arm C.The median ages were 49, 50 and 46, respectively (p=0.11). Median follow-up was 39 (3-193) months. Stage, lymphovascular and perineural invasion, receptor patern, and menopausal status were similar in the 3 treatment arms, but HER2 positivity was significantly lower in arm A, compared to arms B and C (25.7%, 53.1%, 41.5% in arms A, B and C, respectively; p<0.001). Also grade 3 tumors were significantly less frequent in treatment arm A compared to arm B and C (27.3%, 56.8% and 49.2%, respectively, p=0.01). Afterunivariate and multivariate analysis were performed, 3-year DFS rates were 89%, 81%, and 75%, respectively (p=0.12) and three year OS rates were 96.6%, 89%, and 75% (p=0.62). Conclusions: In this study, no significant difference was found between adjuvant dose dense and conventional taxane treatment regimens.
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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.
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Acupuncture as a Complementary Treatment for Cancer Patients Receiving Chemotherapy
Tas, Demet,Uncu, Dogan,Sendur, Mehmet Ali,Koca, Nuran,Zengin, Nurullah Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7
Background: Medical treatment for eliminating the side effects of cancer therapy may not always be efficacious. Acupuncture is one of the most widely accepted alternative and complementary therapies in use today. In this study, we investigated the efficacy of acupuncture in patients experiencing cancer treatment side effects, including nausea, vomiting, pain, poor sleep quality and anxiety. Materials and Methods: A total of 45 inpatients who underwent chemotherapy between February and April 2013 in the Oncology Department of Numune Hospital were included in our study. Acupuncture was administered to the patients one day prior to chemotherapy, on the day of chemotherapy and one day after chemotherapy. The patients were evaluated on nausea, vomiting, pain, sleep quality and anxiety before the chemotherapy and on the $4^{th}$ day of chemotherapy. Results: Of the 45 patients included in the study, 18 (40%) were female and 27 (60%) were male. A total of 25 (55.6%) had an elementary school education; 32 patients (71%) had stage 4 cancer and were treated with palliative chemotherapy (the patient characteristics are shown in Table 1). Statistically significant decreases (p<0.001) in pain, nausea, vomiting, insomnia and anxiety scores were observed after the acupuncture treatment compared to baseline. There were no differences in the age, gender, education level, stage or metastasis levels between the patient groups whose symptoms improved or were unchanged. Conclusions: Our study showed that acupuncture has positive effects in cancer treatment patients who experience nausea, vomiting, pain, poor sleep quality and anxiety as side effects of chemotherapy. Chemotherapy-related side effects in cancer patients could be decreased by the concurrent use of acupuncture.
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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.
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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.
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Behnam Firouzi,Ahmad Abbasi,Polat Sendur 국제구조공학회 2021 Smart Structures and Systems, An International Jou Vol.28 No.1
In this paper we study the static deflection, natural frequency, primary resonance of an electrostatically actuated cracked gas sensor. Besides, a novel hybrid metaheuristic algorithm is proposed to detect the location and depth of possible crack on the microcantilever systems. The gas sensor configuration consists of a microcantilever with a rigid plate attached to its end. The nonlinear effects of the electrostatic force and fringing field are taken into account in the mathematical model. The crack is represented by a rotational spring. In the first part, the effect of crack on the static and dynamic pull-in instability are studied. The equations of motion are solved by the application of the perturbation methods. Next, an inverse problem is formulated to predict the location and depth of the crack in the gas sensor. For that purpose, the weighted squared difference of the analytical and predicted frequency response is considered as the objective function. The location and depth of the crack in the microsystem are determined using the hybrid Harris Hawk and Nelder Mead optimization algorithms. The accuracy and efficiency of the proposed algorithm are compared with the HHO, DA, GOA, and WOA algorithms. Taguchi design of experiments method is used in order to tune the parameters of optimization algorithms systematically. It is shown that the proposed algorithm can predict the exact location and depth of the open-edge crack on an electrostatically actuated microbeam with proof mass.
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Recurrence Risk and Prognostic Parameters in Stage I Rectal Cancers
Cihan, Sener,Kucukoner, Mehmet,Ozdemir, Nuriye,Dane, Faysal,Sendur, Mehmet Ali Nahit,Yazilitas, Dogan,Urakci, Zuhat,Durnali, Ayse,Yuksel, Sinemis,Aksoy, Sercan,Colak, Dilsen,Seker, Mehmet Metin,Taskoy Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13
Background: The standard therapy for stage I rectum cancer is surgical resection. Currently, there is no strong evidence to suggest that any type of adjuvant therapy is beneficial. The risks of local relapse and distant metastasis are higher in rectal tumors. Therefore, while there is no clearly defined absolute indication for adjuvant therapy in lymph node negative colon cancers, rectum tumors that are T3N0 and higher require adjuvant treatment. Due to the more aggressive nature of rectal cancers, we explored the clinical and pathologic factors that could predict the risk of relapse in Stage I (T1-T2) disease and whether there was any progression-free survival benefit to adjuvant therapy. Materials and Methods: This multicenter study was carried out by the Anatolian Society of Medical Oncology. A total of 178 patients with rectal cancers who underwent curative surgery between January 1994 and August 2012 in 13 centers were included in the study. Patient demographics, including survival data and tumor characteristics were obtained from medical charts. Results: The median age was 58 years (range 26-85 years). Most tumors were well or moderately differentiated. For adjuvant treatment, 13 patients (7.3%) received radiotherapy alone, 12 patients (6.7%) received chemotherapy alone and 15 patients (8.4%) were given chemoradiotherapy. Median follow up was 29 months (3-225 months). Some 42 patients (23.6%) had relapse during follow up; 30 with local recurrence (71.4%) whereas 12 (28.6%) were distant metastases. Among the patients, 5-year DFS was 64% and OS was 82%. Mucinous histology and receiving adjuvant therapy were found to have statistically insignificant correlations with relapse and survival. Conclusions: In our retrospective analysis, approximately one quarter of patients exhibited either local or systemic relapse. The rates of relapse were slightly higher in the patients who had no adjuvant therapy. There may thus be a role for adjuvant therapy in high-risk stage I rectal tumors.
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