Investigation of Antitumor Effects of Sorafenib and Lapatinib Alone and in Combination on MCF-7 Breast Cancer Cells

Kacan, Turgut,Altun, Ahmet,Altun, Gulsah Gultekin,Kacan, Selen Baloglu,Sarac, Bulent,Seker, Mehmet Metin,Bahceci, Aykut,Babacan, Nalan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Background: Breast cancer evolution and tumor progression are controlled by complex interactions between steroid receptors and growth factor receptor signaling. Aberrant growth factor receptor signaling can augment or suppress estrogen receptor function in hormone-dependent breast cancer cells. Thus, we aimed to investigate antitumor effects of sorafenib and lapatinib alone and in combination on MCF-7 breast cancer cells. Materials and Methods: Cytotoxicity of the sorafenib and lapatinib was tested in MCF-7 cells by XTT assays. 50, 25, 12.5 and $6.25{\mu}M$ concentrations of sorafenib and 200, 100, 50 and $25{\mu}M$ concentrations of lapatinib were administered alone and in combination. Results were evaluated as absorbance at 450nM and $IC_{50}$ values are calculated according to the absorbance data Results: Both sorafenib and lapatinib showed concentration dependent cytotoxic effects on MCF-7 cells. Sorafenib exerted cytotoxic effects with an $IC_{50}$ value of $32.0{\mu}M$; in contrast with lapatinib the $IC_{50}$ was $136.6{\mu}M$. When sorafenib and lapatinib combined, lapatinib increased cytotoxic effects of sorafenib at its ineffective concentrations. Also at the concentrations where both drugs had cytotoxic effects, combination show strong anticancer effects and killed approximately 70 percent of breast cancer cells. Conclusions: Combinations of tyrosine kinase inhibitors and cytotoxic agents or molecular targeted therapy has been successful for many types of cancer. The present study shows that both sorafenib and lapatinib alone are effective in the treatment of breast cancer. Also a combination of these two agents may be a promising therapeutic option in treatment of breast cancer.

Could the Neutrophil to Lymphocyte Ratio be a Poor Prognostic Factor for Non Small Cell Lung Cancers?

Kacan, Turgut,Babacan, Nalan Akgul,Seker, Metin,Yucel, Birsen,Bahceci, Aykut,Eren, Ayfer Ay,Eren, Memet Fuat,Kilickap, Saadettin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5

Background: Although many prognostic factors have been identified for lung cancers, new ones are needed to determine the course of the disease. Recently, a high neutrophil to lymphocyte ratio (NLR) prior to surgery or treatment has been shown to be an indicator of prognosis for cancer. The aim of this study was to investigate the value of NLR as a prognostic factor and the correlation between NLR and other probable clinical prognostic factors in non small cell lung cancer patients prior to treatment. Materials and Methods: Data of patients who were diagnosed with non-small cell lung cancer in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR was calculated before the application of any treatment. Results: A total of 299 patients, 270 (90%) males and 29 (10%) females, were included in the study. Age (p<0.001) stage (p<0.001), Eastern Cooperative Oncology Group performance status (p<0.001), weight loss (p<0.001), anemia (p<0.001), histopatology (p<0.001), NLR ${\geq}3$ (p=0.048), NLR ${\geq}4$ (p=0.025) and NLR ${\geq}5$ (p=0.018) were found to be the prognostic factors. Age, anemia, Eastern Cooperative Oncology Group performance status, the stage, NLR (${\geq}5$) were an independent prognostic factors. There was a positive correlation between NLR and the Eastern Cooperative Oncology Group performance status (0.23, p=0.001), the C reactive protein levels (r=0.36, p<0.001). Conclusions: Prior to treatment high NLR was found as an independent poor prognosis factor. Besides, NLR correlated with Eastern Cooperative Oncology Group performance status and the C reactive protein levels.

Lack of Association between the MTHFR C677T Polymorphism and Lung Cancer in a Turkish Population

Yilmaz, Meral,Kacan, Turgut,Sari, Ismail,Kilickap, Saadettin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Background: In this case-control study, we aimed to investigate the relationship between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and lung cancer. Materials and Methods: Total 200 individuals including 100 patients with lung cancer and 100 controls were analyzed. Genotyping of MTHFR C677T was performed using PCR and RFLP methods. Results: The majority of the patients were men and 90% were smokers. We found that the risk ratio for development of LC was 13-times higher in smokers compared with non-smokers between patient and control groups in our study (OR:13.5, 95%CI:6.27-29.04, p:0.0001). Besides, the risk ratio for development of LC was nine times higher in individuals with cancer history in their family than those without cancer history (OR:9.65, 95%CI: 2.79-33.36; p:0.0001). When genotype distributions and allele frequencies were analyzed in the study groups, no significant difference was apparent (${\chi}^2$:0.53, p=0.76). In addition, no correlation between genotypes of MTHFRC677T polymorphism and histological type of LC was found (${\chi}^2$:0.99, p=0.60). Conclusions: These results suggest that there was no association between the MTHFR C677T polymorphism and lung cancer in the Turkish population.

Survival Analysis and Prognostic Factors for Neuroendocrine Tumors in Turkey

Yucel, Birsen,Babacan, Nalan Akgul,Kacan, Turgut,Eren, Ayfer Ay,Eren, Mehmet Fuat,Bahar, Seher,Celasun, Mustafa Gurol,Seker, Mehmet Metin,Hasbek, Zekiye Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Background: This study aimed to determine the demographical distribution, survival and prognostic factors for neuroendocrine tumors monitored in our clinic. Materials and Methods: Data for 52 patients who were admitted to Cumhuriyet University Medical Faculty Training Research and Practice Hospital Oncology Center between 2006 and 2012 and were diagnosed and treated for neuroendocrine tumors were investigated. Results: Of the total, 30 (58%) were females and 22 (42%) were males. The localization of the disease was gastroenteropancreatic in 29 (56%) patients and other sites in 23 (44%). The most frequently involved organ in the gastroenteropancreatic system was the stomach (n=10, 19%) and the most frequently involved organ in other regions was the lungs (n=10, 19%). No correlation was found between immunohistochemical staining for proteins such as chromogranin A, synaptophysin, and NSE and the grade of the tumor. The patients were followed-up at a median of 24 months (1-90 months). The three-year overall survival rate was 71%: 100% in stage I, 88% in stage II, 80% in stage III, and 40% in stage IV. The three-year survival rate was 78% in tumors localized in the gastroenteropancreatic region, and 54% in tumors localized in other organs. In the univariate analysis, gender, age, performance status of the patients, grade, localization, surgical treatment, and neutrophil/lymphocyte ratio (${\leq}5$ versus >5) affected the prognosis of the patients. Conclusions: Most of the tumors were localized in the gastroenteropancreatic region, and the three-year survival rate in tumors localized in this region was better than the tumors localized in other sites. Surgical treatment was a positive independent prognostic factor, whereas Grade 3 and a neutrophil/lymphocyte ratio of >5 were negative independent prognostic factors.

Lung Cancer in Women: A Single Institution Experience with 50 Patients

Babacan, Nalan Akgul,Yucel, Birsen,Kilickap, Saadettin,Seker, Mehmet Metin,Kacan, Turgut,Olcas, Ilknur Koc,Eren, Ayfer Ay,Odabas, Hatice Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Background: Lung cancer is the most common cause of cancer-related death worldwide. The incidence of lung cancer is aproximately 7-8 thousand percent in Turkish women. In this study, we aimed to evaluate the clinical, pathological properties and survival data of female patients with lung cancer who were treated in our center. Materials and Methods: From 2007 to 2012, 50 women with lung cancer were enrolled. Patient data were evaluated retrospectively. Results: The median age was 61 (40-81). Forty patients (80%) were diagnosed with non small cell lung cancer (NSCLC), 10 patients (20%) were small cell carcinoma (SCC). Twelve (24%) patients were smokers and 13 of 16 non-smokers had a history of exposure to asbestos. The most common histologic subtype was adenocarcinoma (46%) and this accounted for 71% in patients with exposure to asbestos. The most common initial Eastern Cooperative Oncology Group (ECOG) performance score was 1 (24 patients, 48%) and initial stage was IV (25 patients, 50%) in the study group. During the median 15 months (1-96 months) followup period: 1 year overall survival (OS) was 68%, 2year overall survival was 36% and the median survival time was 19 months. According to univariate analysis, poor ECOG performance status, advanced stage, anemia and weight loss at time of diagnosis were negative prognostic factors. However, adenocarcinoma sub-type was a positive prognostic factor. Conclusions: In this study NSCLC sub-type, poor ECOG performance score, advanced stage, anemia and weight loss were prognostic factors in Turkish women with lung cancer.

Potential Impact of Atelectasis and Primary Tumor Glycolysis on F-18 FDG PET/CT on Survival in Lung Cancer Patients

Hasbek, Zekiye,Yucel, Birsen,Salk, Ismail,Turgut, Bulent,Erselcan, Taner,Babacan, Nalan Akgul,Kacan, Turgut Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.9

Background: Atelectasis is an important prognostic factor that can cause pleuritic chest pain, coughing or dyspnea, and even may be a cause of death. In this study, we aimed to investigate the potential impact of atelectasis and PET parameters on survival and the relation between atelectasis and PET parameters. Materials and Methods: The study consisted of patients with lung cancer with or without atelectasis who underwent $^{18}F$-FDG PET/CT examination before receiving any treatment. $^{18}F$-FDG PET/CT derived parameters including tumor size, SUVmax, SUVmean, MTV, total lesion glycosis (TLG), SUV mean of atelectasis area, atelectasis volume, and histological and TNM stage were considered as potential prognostic factors for overall survival. Results: Fifty consecutive lung cancer patients (22 patients with atelectasis and 28 patients without atelectasis, median age of 65 years) were evaluated in the present study. There was no relationship between tumor size and presence or absence of atelectasis, nor between presence/absence of atelectasis and TLG of primary tumors. The overall one-year survival rate was 83% and median survival was 20 months (n=22) in the presence of atelectasis; the overall one-year survival rate was 65.7% (n=28) and median survival was 16 months (p=0.138) in the absence of atelectasis. With respect to PFS; the one-year survival rate of AT+ patients was 81.8% and median survival was 19 months; the one-year survival rate of AT-patients was 64.3% and median survival was 16 months (p=0.159). According to univariate analysis, MTV, TLG and tumor size were significant risk factors for PFS and OS (p<0.05). However, SUVmax was not a significant factor for PFS and OS (p>0.05). Conclusions: The present study suggested that total lesion glycolysis and metabolic tumor volume were important predictors of survival in lung cancer patients, in contrast to SUVmax. In addition, having a segmental lung atelectasis seems not to be a significant factor on survival.

Predictive Role of Neutrophil Gelatinase-Associated Lipocalin in Early Diagnosis of Platin-Induced Renal Injury

Seker, Mehmet Metin,Deveci, Koksal,Seker, Ayse,Sancakdar, Enver,Yilmaz, Ali,Turesin, A. Kerim,Kacan, Turgut,Babacan, Nalan A. Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.2

Background: Acute kidney injury is an important issue in chemotherapy receiving patients an neutrophil gelatinase-associated lipocalin has been proposed as a novel marker. We here aimed to assess the role of urinary levels for assessment after platin exposure. Materials and Methods: Patients who had treated with cisplatin or carboplatin or oxaliplatin containg regimens were included in this study. Baseline and postchemotherapy serum urea, creatinine, urine neutrophil gelatinase-associated lipocalin and urine creatinine levels were determined. To avoid the effects of hydration during chemotherapy infusion the urinary neutrophil gelatinase-associated lipocalin/urine creatinine ratio was used to determine acute kidney injury. Results: Of a total of 42 patients receiving platin compounds,14 (33.3%) received cisplatin containing regimens, 14 (33.3%) received carboplatin and 14 (33.3%) oxaliplatin. The median age was 60 (37-76) years. Nineteen of the patients (45.2%) had lung cancer, 12 (28.6%) colorectal cancer and 11 (26.2%) others. The median pre and post chemotherapy urine neutrophil gelatinase-associated lipocalin/urine creatinin ratio was 15.6 ng/mg and 35.8 ng/mg (p=0.041) in the cisplatin group, 32.5 ng/mg and 86.3 ng/mg (p=0.004) in the carboplatin group and 40.9 ng/mg and 62.3 ng/mg (p=0.243) in the oxaliplatin group. Conclusions: Nephrotoxicity is a serious side effect of chemotherapeutic agentslike cisplatin and carbopaltin, but only to a lower extent oxaliplatin. All platin compounds must be used carefully and urine neutrophil gelatinase-associated lipocalin measurement seems to be promising in detecting acute kidney injury earlier than with creatinine.

Multicenter Epidemiologic Study on Hepatocellular Carcinoma in Turkey

Can, Alper,Dogan, Erkan,Bayoglu, Ibrahim Vedat,Tatli, Ali Murat,Besiroglu, Mehmet,Kocer, Murat,Dulger, Ahmet Cumhur,Uyeturk, Ummugul,Kivrak, Derya,Orakci, Zuat,Bal, Oznur,Kacan, Turgut,Olmez, Sehmus,T Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

Background: Hepatocellular cancer (HCC) is one of the important health problems in Turkey, being very common and highly lethal. The aim of this study was to determine clinical, demographic features and risk factors. Materials and Methods: Nine hundred and sixth-three patients with HCC from 13 cities in Turkey were included in this study. Results: Only 205 (21%) of the 963 patients were women, with a male:female predominance of 4.8:1 and a median age of 61 years. The etiologic risk factors for HCC were hepatitis B in 555 patients (57.6%), 453 (81%) in men, and 102 (19%) in women, again with male predominance, hepatitis C in 159 (16.5%), (14.9% and 22.4%, with a higher incidence in women), and chronic alcohol abuse (more than ten years) in 137 (14.2%) (16.8% and 4.9%, higher in males). The Child-Pugh score paralleled with advanced disease stage amd also a high level of AFP. Conclusions: According to our findings the viral etiology (hepatitis B and hepatitis C infections) in the Turkish population was the most important factor in HCC development, with alcohol abuse as the third risk factor. The Child-Pugh classification and AFP levels were determined to be important prognostic factors in HCC patients.