Browsing by Author "Goksel G."

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    The role of virulent Helicobacter pylori strains in the etiopathogenesis of coronary artery disease; [Virulan Helicobacter pylori suslarinin koroner arter hastaligi etyopatogenezindeki rolu]
    (1999) Yuceyar H.; Saruc M.; Arslan S.; Goksel G.; Ozbakkaloglu B.; Uyanik B.S.; Yigitoglu R.; Sengil A.Z.
    Epidemiological studies have shown a positive correlation between coronary artery disease (CAD) and gastric Helicobacter pylori (H. pylori) infection. The possible mechanism by which H. pylori could increase the risk of CAD is chronic inflammation. More virulent H. pylori strains bearing the cytotoxin associated gene-A (CagA) can induce much more inflammation than CagA negative strains. The aim of our study was to assess the role of virulent H. pylori strains and inflammatory response in the pathogenesis of CAD. We studied 30 patients with CAD, age and sex being matched with 30 controls of similar social class. We determined the presence of H. pylori infection by rapid urease test, histology and serology (anti-H. pylori IgG). CagA status, serum tumor necrosis factor-alpha (TNF-α), gastrin and fibrinogen levels were also studied. The presence of H. pylori infection was statistically equal in CAD group (93.3%) and controls (86.6%)(p = 0.705). Serum CagA titers were 28.13 ± 9.21 U and 18.32 ± 5.8 U in the CAD and control group respectively. Serum TNF-α levels were 15.21 ± 4.30 pg/ml in the CAD group and 5.36 ± 2.41 pg/ml in the control group. Serum CagA and TNF-α levels showed a significant difference between the two groups (p = 0.000). Patients with CAD had a higher prevalence of CagA-positive strains than controls (67.8% versus 42.3%; p = 0.021). The serum gastrin level was higher in CAD but there was no significant difference between two groups (p = 0.379). Fibrinogen levels of the CAD group were significantly higher than those of the control (370 ± 51 mg/ml and 247 ± 43 mg/ml, p = 0.001). Further more, numbers of occluded vessels in CAD patients were positively correlated with both cagA positivity and TNF-α levels. In conclusion, CagA bearing strains of H. pylori may increase the risk of CAD by inducing chronic inflammation and increasing the expression of cytokines and procoagulant substance.
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    The effect of CagA status on response to Helicobacter pylori eradication therapy in Western Turkey
    (Associacao Brasileira de Divulgacao Cientifica, 2001) Saruç M.; Goksel G.; Ozkaya S.; Guclu F.; Ozbakkaloglu B.; Yuceyar H.
    If cytotoxin-associated gene A (CagA) status affects the response rates of therapy, then it may be possible to predict Helicobacter pylori eradication rates. We aimed to evaluate the response to eradication treatment of H. pylori infection in CagA-positive and CagA-negative patients. A total of 184 patients (93 males, 91 females, mean age 42.6 ± 12.8 years) with H. pylori-positive chronic gastritis were studied. Subjects underwent a gastroscopy and biopsy specimens were taken from the gastric antrum, body, and fundus. Before the eradication therapy was given all patients were tested for CagA, TNF-α and gastrin levels. They were then prescribed lansoprazole (30 mg bid), clarithromycin (500 mg bid), and amoxicillin (1.0 mg bid) for one week. On the 8th week a second endoscopy was performed and further biopsy specimens were obtained from the same sites as in the initial endoscopy. One hundred and twenty-seven patients (69.1%) were found to be CagA positive and 57 patients (30.9%) were CagA negative. The total eradication rate was 82.6%. In the CagA-positive group this rate was 87.4%, and in the CagA-negative group it was 71.9% (P = 0.019). TNF-α levels were higher in the CagA-positive than in the CagA-negative group (P = 0.001). However, gastrin levels were not different between groups (P = 0.421). Our findings revealed that CagA-negative status might be a risk factor for failure of H. pylori triple therapies. The CagA pathogenicity island gives a growth advantage to H. pylori strains and has been associated with an increase in the inflammatory response at the gastric mucosal level. These properties could make CagA-positive H. pylori strains more susceptible to antibiotics.
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    Potential predictive factors for response to weekly paclitaxel treatment in patients with metastatic breast cancer
    (E.S.I.F.T. srl, 2005) Sezgin C.; Karabulut B.; Uslu R.; Sanli U.A.; Goksel G.; Zekioglu O.; Ozdemir N.; Goker E.
    The authors compare results obtained from weekly paclitaxel treatment in advanced breast cancer patients with biological and clinical prognostic factors. Expression of c-erbB-2, Ki-67, p53 and hormone receptors (HR) was examined by immunohistochemistry in samples of breast tissue from 30 patients. Univariate analysis showed that Ki-67 positivity and low performance status (PS) were associated with poor outcome (P <0.05). We observed that expression of p53 and c-erbB-2 did not have any negative effect on response to chemotherapy and survival. HR-negative patients had better response and slightly statistically significant overall survival (OS) rates compared to HR-positive patients (P >0.05). In a multivariate analysis low PS was the only significant predictor of shorter survival (P <0.05). In conclusion, while the expression of p53 and c-erbB-2 did not have any effect on treatment results, negative Ki-67 expression and negative HR status were associated with better OS in this patient population. PS was the only significant predictor for OS. © E.S.I.F.T. srl - Firenze.
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    Gemcitabine treatment in patients with inoperable locally advanced/metastatic pancreatic cancer and prognostic factors
    (2005) Sezgin C.; Karabulut B.; Uslu R.; Sanli U.A.; Goksel G.; Yuzer Y.; Goker E.
    Objective. Most patients with pancreatic cancer show an inoperable locally advanced/ metastatic tumour at the time of diagnosis. The present study was aimed at determining the prognostic factors in patients with advanced pancreatic carcinoma treated with gemcitabine. Material and methods. Sixty-seven unresectable or metastatic pancreatic cancer patients treated with gemcitabine were included in the study and a total of 258 cycles of treatment were applied. Results. The overall response rate was 5%. Thirty-one percent of the patients had stable disease, whereas progressive disease was seen in 49%. Clinical benefit response rate was 15%. The median duration of response was 7.3 months. Median progression-free survival was 3 months, while median overall survival was 9 months. Univariate analysis revealed that worse results were found in patients with performance status (PS) =2, and in patients with primary tumour location in the body or tail of the pancreas (p <0.05). Multivariate analysis of data revealed that the most important factor was PS of the patient, as the patients with PS =2 had worse results than the patients with PS =0-1 (p <0.05). Conclusions. Low PS is a negative predictive factor for the survival of patients with advanced pancreatic carcinoma treated with gemcitabine. © 2005 Taylor & Francis.
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    Role of intercellular communications in breast cancer multicellular tumor spheroids after chemotherapy
    (Tech Science Press, 2006) Oktem G.; Bilir A.; Ayla S.; Yavasoglu A.; Goksel G.; Saydam G.; Uysal A.
    Tumor heterogeneity is an important feature that is especially involved in tumor aggressiveness. Multicellular tumor spheroids (MTS) may provide some benefits in different steps for investigation of the aggregation, organization, differentiation, and network formation of tumor cells in 3D space. This model offers a unique opportunity for improvements in the capability of a current strategy to detect the effect of an appropriate anticancer agent. The aim of this study was to investigate the cellular interactions and morphological changes following chemotherapy in a 3D breast cancer spheroid model. Distribution of the gap junction protein "connexin-43" and the tight junction protein "occludin" was investigated by immunohistochemistry. Cellular interactions were examined by using transmission and scanning electron microscopies as well as light microscopy with Giemsa staining after treating cells with doxorubicin, docetaxel, and doxorubicin/docetaxel combination. Statistical analyses showed significant changes and various alterations that were observed in all groups; however, the most prominent effect was detected in the doxorubicin/docetaxel combination group. Distinct composition as a vessel-like structure and a pseudoglandular pattern of control spheroids were detected in drug-administered groups. Immunohistochemical results were consistent with the ultrastructural changes. In conclusion, doxorubicin/ docetaxel combination may be more effective than the single drug usage as shown in a 3D model. The MTS model has been found to be an appropriate and reliable method for the detection of the changes in the expression of cellular junction proteins as well as other cellular proteins occurring after chemotherapy. The MTS model can be used to validate the effects of various combinations or new chemotherapeutic agents as well as documentation of possible mechanisms of new drugs. Copyright © 2006 Cognizant Comm. Corp.
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    Serum Her-2/neu and survivin levels and their relationship to histological parameters in early-stage breast cancer
    (Cambridge Medical Publications, 2007) Goksel G.; Taneli F.; Uslu R.; Ulman C.; Dinc G.; Coskun T.; Kandiloglu A.R.
    This study was conducted to investigate the serum levels of her-2/neu and survivin in patients with early-stage breast cancer and their relationship with known histological parameters. Forty-one patients with early-stage breast cancer were investigated. Serum samples were collected from patients on their first admission before adjuvant chemotherapy, and from healthy controls. Serum her-2/neu and survivin levels were determined using an enzyme-linked immunosorbent assay. There was no difference in the levels of serum her-2/neu and survivin between the breast cancer patients and the control group. Serum her-2/neu concentration showed moderate correlations with disease stage and the Ki-67 level, and the serum survivin level showed a moderate correlation with progesterone receptor concentration. Serum levels of her-2/neu and survivin were not significantly related to age and histological parameters in patients with early-stage breast cancer. However, much research continues on the prognostic value of serum her-2/neu and survivin levels, and important new knowledge may ultimately emerge. Copyright © 2007 Cambridge Medical Publications.
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    Gemcitabine Alone versus combination of Gemcitabine and Cisplatin for the Treatment of Patients with Locally Advanced and/or Metastatic Pancreatic Carcinoma: A Retrospective Analysis of multicenter study
    (SAP - Slovak Academic Press, spol. s.r.o., 2012) Inal A.; Kos F.T.; Algin E.; Yildiz R.; Dikiltas M.; Unek I.T.; Colak D.; Elkiran E.T.; Helvaci K.; Geredeli C.; Dane F.; Balakan O.; Kaplan M.A.; Durnali A.G.; Harputoglu H.; Goksel G.; Ozdemir N.; Buyukberber S.; Gumus M.; Kucukoner M.; Ozkan M.; Uncu D.; Benekli M.; Isikdogan A.
    The majority of patients with pancreatic cancer is of advanced disease. Several randomized Phase II and III trials suggest that the combination of gemcitabine and cisplatin (GemCis) response rates were higher than Gemcitabine (Gem) alone, however the trials were not enough powered to indicate a statistically significant prolongation of survival in patients with advanced pancreatic adenocarcinoma. The aim of this retrospective multicenter study is to evaluated the efficiency of Gem alone versus GemCis in patients with locally advanced and/or metastatic pancreatic adenocarcinoma. A total of 406 patients, from fourteen centers were evaluated retrospectively. All patients received Gem or GemCis as first-line treatment between September 2005 to March 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. There were 156 patients (M: 98, F: 58) in Gem arm and 250 patients (M: 175, F: 75) in the combination arm. Gemcitabin arm patients older than the combination arm (median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25.2% vs 11.3%, p=0.001) and dose delay (34% vs 16.8%, p=0.001). Among patients with the combination and Gemcitabin arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the Gem arm (69.0% vs 49.7%, p=0.001). PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance (8.9 vs 6.0, p=0.08). OS was not significantly superior in the GemCis arm (12.0 vs 10.2, p>0.05). Grade III-IV hematologic and nonhematologic toxicity were higher in the combination arm. PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. OS was not significantly superior in the GemCis arm.
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    Prognostic factors in patients with advanced pancreatic cancer treated with gemcitabine alone or gemcitabine plus cisplatin: Retrospective analysis of a multicenter study
    (2012) Inal A.; Kos F.T.; Algin E.; Yildiz R.; Berk V.; Tugba Unek I.; Colak D.; Kucukoner M.; Tamer Elkiran E.; Helvaci K.; Geredeli C.; Dane F.; Balakan O.; Ali Kaplan M.; Gok Durnali A.; Harputoglu H.; Goksel G.; Ozdemir N.; Buyukberber S.; Gumus M.; Ozkan M.; Benekli M.; Isikdogan A.
    Purpose: The majority of patients with pancreatic cancer present with advanced disease. Systemic chemotherapy for patients with pancreatic cancer has limited impact on overall survival (OS). Patients eligible for chemotherapy should be selected carefully. The aim of this study was to analyse prognostic factors for OS in advanced pancreatic cancer patients treated with first-line palliative chemotherapy with gemcitabine alone or gemcitabine plus cisplatin. Methods: We retrospectively reviewed 343 locally advanced or metastatic pancreatic cancer patients who were treated with gemcitabine or gemcitabine plus cisplatin as first-line chemotherapy between December 2000 and June 2011. Fifteen potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS. Univariate and multivariate statistical methods were used to determine prognostic factors. Results: Among the 15 variables of univariate analysis, 6 were identified to have prognostic significance: stage (p<0.001), cholestasis (p=0.02), weight loss, prior pancreatectomy, serum CEA level (p<0.001) and serum CA19-9 level (p<0.001). In addition, age, chemotherapy and liver metastasis were of borderline significance (p=0.06). Multivariate analysis (Cox proportional hazard model) included the 6 significant prognostic factors ofunivariate analysis and showed that stage was independent prognostic factor for OS, as were weight loss, and serum CEA level. Conclusion: Stage, weight loss, and serum CEA level were identified as important prognostic factors for OS in advanced pancreatic cancer patients. These findings may also facilitate pretreatment prediction of OS and can be used for selecting patients for treatment. © 2012 Zerbinis Medical Publications.
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    Is lymph node ratio prognostic factor for survival in elderly patients with node positive breast cancer?: The Anatolian society of medical oncology
    (2013) Inal A.; Akman T.; Yaman S.; Ozturk S.C.; Geredeli C.; Bilici M.; Inanc M.; Harputoglu H.; Demirci U.; Suner A.; Cinkir H.Y.; Alici S.; Colak D.; Sonmez O.U.; Goksel G.; Dogu G.G.; Engin H.; Unal O.U.; Tamozlu T.; Buyukberber S.; Boruban C.M.; Isikdogan A.
    Several studies have now demonstrated that the lymph node ratio (LNR), as a superior indicator of axillary tumor burden to the number of excised nodes. While, about the prognostic value of LNR on the the survival of elderly patients is limited. The aim of this retrospective multicenter study is to evaluate the prognostic value of lymph node ratio in elderly patients with node positive breast cancer. METHODS: Onehundredeightyfour patient with operable breast cancer, recruited from 17 institutions, were enrolled into the retrospectively study Eleven potential prognostic variables were chosen for analysis in this study Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. RESULT: Among the eleven variables of univariate analysis, four variables were identified to have prognostic significance for Overall survival (OS): patholo^c tumor size (T), No. oppositive nodes (N), LNR and estrogen receptor-positive (ER). Among the eleven variables of univariate analysis, two variables were identified to have prognostic significance for Disease-free survival (DFS): N and LNR. Multivariate analysis by Cox proportional hazard model showed that T, LNR and ER were considered independent prognostic factors for OS. Furthermore, LNR was considered independent prognostic factors for DFS. CONCLUSION: In conclusion, the LNR was associated with the prognostic importance for DFS and OS in elderly patients who were administered adjuvant treatments.
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    Endocrine therapy alone vs chemotherapy plus endocrine therapies for the treatment of elderly patients with endocrine-responsive and node positive breast cancer: A retrospective analysis of a multicenter study (Anatolian Society of Medical Oncology)
    (2013) Inal A.; Akman T.; Yaman S.; Demir Ozturk S.; Geredeli C.; Bilici M.; Inanc M.; Harputoglu H.; Demirci U.; Balakan O.; Yesil Cinkir H.; Alici S.; Uysal Sonniez O.; Goksel G.; Gokoz Dogu G.; Umit Unal O.; Tamozlu T.; Buyukberber S.; Melih Bomban C.; Isikdogan A.
    Purpose: The extra benefit of adding chemotherapy to effective endocrine therapy (ET) has not been clearly or consistently identified in patients older than 70 years with estrogen receptor (ER) positive and node positive breast cancer. The aim of this study was to evaluate the efficacy of adjuvant ET vs chemotherapy plus endocrine therapies (Chemo/ET) in such patients. Methods: In this retrospective multicenter study 191 patients ≥ 70 years with operated hormone receptor positive breast cancer, who were administered adjuvant ET or Chemo/ET were assessed. Results: The median patient follow-up time was 29.0 months (range 1-252). Therefore disease free survival (DFS) and overall survival (OS) analysis was limited, due to the rather short median follow-up, and only 30-month cumulative percentages are reported herein. The 30-month DFS rates were 50.0% in the ET arm and 49.0% in the Chemo/ET arm (p=0.79). The 30-month OS rates were 86% in the ET arm and 96.0% in the Chemo/ET arm (p=0.08). Cox proportional hazard model showed that only surgery was independent prognostic factor for survival (p=0.047), while tumor size showed a strong trend for statistical significance (p=0.051). Conclusion: The addition of chemotherapy to endocrine therapy in older patients has no significant impact on DFS and OS.
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    The clinical and pathological features of 133 colorectal cancer patients with brain metastasis: a multicenter retrospective analysis of the Gastrointestinal Tumors Working Committee of the Turkish Oncology Group (TOG)
    (Humana Press Inc., 2014) Tanriverdi O.; Kaytan-Saglam E.; Ulger S.; Bayoglu I.V.; Turker I.; Ozturk-Topcu T.; Cokmert S.; Turhal S.; Oktay E.; Karabulut B.; Kilic D.; Kucukzeybek Y.; Oksuzoglu B.; Meydan N.; Kaya V.; Akman T.; Ibis K.; Saynak M.; Sen C.A.; Uysal-Sonmez O.; Pilancı K.N.; Demir G.; Saglam S.; Kocar M.; Menekse S.; Goksel G.; Yapar-Taskoylu B.; Yaren A.; Uyeturk U.; Avci N.; Denizli B.; Ilis-Temiz E.
    Brain metastasis in colorectal cancer is highly rare. In the present study, we aimed to determine the frequency of brain metastasis in colorectal cancer patients and to establish prognostic characteristics of colorectal cancer patients with brain metastasis. In this cross-sectional study, the medical files of colorectal cancer patients with brain metastases who were definitely diagnosed by histopathologically were retrospectively reviewed. Brain metastasis was detected in 2.7 % (n = 133) of 4,864 colorectal cancer patients. The majority of cases were male (53 %), older than 65 years (59 %), with rectum cancer (56 %), a poorly differentiated tumor (70 %); had adenocarcinoma histology (97 %), and metachronous metastasis (86 %); received chemotherapy at least once for metastatic disease before brain metastasis developed (72 %), had progression with lung metastasis before (51 %), and 26 % (n = 31) of patients with extracranial disease at time the diagnosis of brain metastasis had both lung and bone metastases. The mean follow-up duration was 51 months (range 5–92), and the mean survival was 25.8 months (95 % CI 20.4–29.3). Overall survival rates were 81 % in the first year, 42.3 % in the third year, and 15.7 % in the fifth year. In multiple variable analysis, the most important independent risk factor for overall survival was determined as the presence of lung metastasis (HR 1.43, 95 % CI 1.27–4.14; P = 0.012). Brain metastasis develops late in the period of colorectal cancer and prognosis in these patients is poor. However, early screening of brain metastases in patients with lung metastasis may improve survival outcomes with new treatment modalities. © 2014, Springer Science+Business Media New York.
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    Prognostic significance of the baseline serum uric acid level in non-small cell lung cancer patients treated with first-line chemotherapy: a study of the Turkish Descriptive Oncological Researches Group
    (Humana Press Inc., 2014) Tanriverdi O.; Cokmert S.; Oktay E.; Pilanci K.N.; Menekse S.; Kocar M.; Sen C.A.; Avci N.; Akman T.; Ordu C.; Goksel G.; Meydan N.
    Non-small cell lung cancer (NSCLC) is one of the most common cancers. Most of the patients are inoperable at the time of diagnosis, and the prognosis is poor. Many prognostic factors have been identified in prior studies. However, it is not clear which factor is more useful. In this study, we investigated whether uric acid, the last breakdown product of purine metabolism in humans, has a prognostic significance in advanced NSCLC. A total of 384 NSCLC patients at stage IIIB/IV and who did not meet exclusion criteria were included in this retrospective cross-sectional study. The patients’ serum uric acid levels before first-line chemotherapy and demographic (age, gender, smoking), clinical (performance status, weight loss, disease stage, first-line treatment regimen), laboratory (hemoglobin, lactate dehydrogenase), and histologic (histologic type, tumor grade) characteristics were recorded. First, a cut-off value was determined for serum uric acid level. Then, the patients were stratified into four groups (quartiles) based on their serum uric acid levels. Descriptive statistics, univariate and multivariate analyses, and survival analyses were used. Majority of the patients were males, smokers and metastatic at time of diagnosis and had history of weight loss and adenocarcinoma upon pathological examination. The serum uric acid levels of all patients were determined as 4.9 ± 2.9 (range 1.9–11.3). The patients were stratified according to quartiles of serum uric acid concentration with cutoff values defined as <3.08 mg/dL (lowest quartile, Group 1), 3.09–5.91 mg/dL (Group 2), 5.92–7.48 mg/dL (Group 3), and >7.49 mg/dL (highest quartile, Group 4). Among the patients who had serum uric acid levels over 7.49, it was observed that those who also had squamous cell carcinoma had a greater rate of brain metastasis, a shorter time lapse until brain metastasis, and lower overall survival rate. It can be assumed that NSCLC patients who had histologically shown squamous cell carcinoma display brain metastasis and poor prognosis. It can be recommended to repeat this study with larger patient series including immunohistochemical, molecular, and wider laboratory investigations. © 2014, Springer Science+Business Media New York.
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    WNT1 gene expression alters in heterogeneous population of prostate cancer cells; decreased expression pattern observed in CD133+/CD44 + prostate cancer stem cell spheroids
    (Journal of B.U.ON., 2014) Goksel G.; Bilir A.; Uslu R.; Akbulut H.; Guven U.; Oktem G.
    Purpose: Established cancer cell lines contain cancer stem cells (CSCs) which can propagate to form three dimensional (3D) tumor spheroids in vitro. Aberrant activation of WNT signaling is strongly implicated in the progression of cancer and controls CSCs properties. In this study we hypothesized that when cells were maintained as spheroids, the structure of CSCs could show differentiation between CSCs and non- CSCs. Methods: CD133+/CD44 + cancer-initiating cells were isolated from DU-145 human prostate cancer cell line monplayer cultures, propagated as tumor spheroids and compared with the remaining heterogeneous cancer cells bulk population. The expression levels of WNTl, FZD1, ADAR, APC, AXIN, BTRC, FRATI and PPARD genes were measured by polymerase chain reaction (PCR) array assay and the protein expression levels of WNT1, FZD and AXIN by immunohistochemistry. Results: The expression levels of WNT pathway-related molecules were found to increase in both CSCs and non-CSCs when CSCs were maintained as spheroids. However, different expression profiles were observed when CSCs and non-CSCs were compared. In spheroids, the expression levels of FZD1, APC, ADAR, WNTl, PPARD genes in CSCs decreased when compared to non-CSCs. Interestingly, when CSCs from spheroids were compared with CSCs from monolayers the most significant decrease was observed in FZD1 and increase in APC genes. Conclusion: It is possible to assume that intracellular signaling of WNT-related molecules in the nucleus and/or cytoplasm might play an important role but it is independent from increased ligand expression and this expression strongly differentiate CSCs and non-CSCs population. This unexpected expression could be important for CSCs behavior and targeting this pathway could have therapeutic implications in cancer.
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    Pathologic and clinical characteristics of elderly patients with breast cancer: A retrospective analysis of a multicenter study (anatolian society of medical oncology)
    (International College of Surgeons, 2014) Ial A.; Akman T.; Yaman S.; Ozturk S.C.; Geredeli C.; Bilici M.; Inanc M.; Harputoglu H.; Demirci U.; Balakan O.; Cinkir H.Y.; Alici S.; Colak D.; Sonmez O.U.; Goksel G.; Dogu G.G.; Engin H.; Unal O.U.; Tamozlu T.; Buyukberber S.; Boruban C.M.; Isikdogan A.
    There is very little information about breast cancer characteristics, treatment choices, and survival among elderly patients. The purpose of this multicenter retrospective study was to examine the clinical, pathologic, and biologic characteristics of 620 breast cancer patients age 70 years or older. Between June 1991 and May 2012, 620 patients with breast cancer, recruited from 16 institutions, were enrolled in the retrospective study. Patients had smaller tumors at diagnosis; only 15% of patients had tumors larger than 5 cm. The number of patients who had no axillary lymph node involvement was 203 (32.7%). Ninety-three patients (15.0%) had metastatic disease at diagnosis. Patients were characterized by a higher fraction of pure lobular carcinomas (75.3%). The tumors of the elderly patients were also more frequently estrogen receptor (ER) positive (75.2%) and progesterone receptor (PR) positive (67.3%). The local and systemic therapies for breast cancer differed according to age. An association between age and overall survival has not been demonstrated in elderly patients with breast cancer. In conclusion, the biologic behavior of older patients with breast cancer differs from younger patients, and older patients receive different treatments.
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    Predictive factors for the development of brain metastases in patients with malignant melanoma: A study by the Anatolian society of medical oncology
    (2014) Gumusay O.; Coskun U.; Akman T.; Ekinci A.S.; Kocar M.; Erceleb O.B.; Yazici O.; Kaplan M.A.; Berk V.; Cetin B.; Taskoylu B.Y.; Yildiz A.; Goksel G.; Alacacioglu A.; Demirci U.; Algin E.; Uysal M.; Oztop I.; Oksuzoglu B.; Dane F.; Gumus M.; Buyukberber S.
    Background: The development of brain metastases (BMs) was associated with poor prognosis in melanoma patients. Patients with BMs have a median survival of <6 months. Melanoma is the third most common tumor to metastasize to the brain with a reported incidence of 10-40 %. Our aim was to identify factors predicting development of BMs and survival. Patients and methods: We performed a retrospective analysis of 470 melanoma patients between 2000 and 2012. The logistic regression analyses were used to identify the clinicopathological features of primary melanoma that are predictive of BMs development and survival after a diagnosis of brain metastases. Results: There were 52 patients (11.1 %) who developed melanoma BMs during the study period. The analysis of post-BMs with Kaplan-Meier curves has resulted in a median survival rate of 4.1 months (range 2.9-5.1 months). On logistic regression analysis site of the primary tumor on the head and neck (p = 0.002), primary tumor thickness (Breslow >4 mm) (p = 0.008), ulceration (p = 0.007), and pathologically N2 and N3 diseases (p = 0.001) were found to be significantly associated with the development of BMs. In univariate analysis, tumor thickness and performance status had a significant influence on post-BMs survival. In multivariate analysis, these clinicopathologic factors were not remained as significant predictive factors. Conclusions: Our results revealed the importance of primary tumor characteristics associated with the development of BMs. Ulceration, primary tumor thickness, anatomic site, and pathologic ≥N2 disease were found to be significant predictors of BMs development. © 2013 Springer-Verlag Berlin Heidelberg.
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    Cancer stem cell differentiation: TGFβ1 and versican may trigger molecules for the organization of tumor spheroids
    (Spandidos Publications, 2014) Oktem G.; Sercan O.; Guven U.; Uslu R.; Uysal A.; Goksel G.; Ayla S.; Bilir A.
    Cancer stem cells (CSCs) have the ability to self-renew similar to normal stem cells. This process is linked with metastasis and resistance to chemotherapy and radiotherapy. In the present study, we constructed an in vitro differentiation model for CSCs. CSCs isolated and proliferated for one passage were maintained as monolayers or spheroid-forming cells with serum included media for differentiation process. Differentiation of adhesion molecules and cellular ultrastructural properties were investigated and compared in both monolayer and spheroid cultures. CD133+/CD44+ cancer-initiating cells were isolated from DU-145 human prostate cancer cell line monolayer cultures and propagated as tumor spheroids and compared with the remaining heterogeneous cancer cell bulk population. Microarray-based gene expression analysis was applied to determine genes with differential expression and protein expression levels of candidates were analyzed by immunohistochemistry. Electron microscopy showed detailed analysis of morphology. TGFβ1 was found to be significantly upregulated in monolayer CSCs. High expression levels of VCAN, COL7A1, ITGβ3, MMP16, RPL13A, COL4A2 and TIMP1 and low expression levels of THBS1, MMP1 and MMP14 were detected when CSCs were maintained as serum-grown prostate CSC spheroids. Immunohistochemistry supported increased immunoreactivity of TGFβ1 in monolayer cultures and VCAN in spheroids. CSCs were found to possess multipotential differentiation capabilities through upregulation and/or downregulation of their markers. TGFβ1 is a triggering molecule, it stimulates versican, Col7A1, ITGβ3 and, most importantly, the upregulation of versican was only detected in CSCs. Our data support a model where CSCs must be engaged by one or more signaling cascades to differentiate and initiate tumor formation. This mechanism occurs with intracellular and extracellular signals and it is possible that CSCc themselves may be a source for extracellular signaling. These molecules functioning in tumor progression and differentiation may help develop targeted therapy.
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    Pretreatment serum albumin level is an independent prognostic factor in patients with stage IIIB non-small cell lung cancer: A study of the Turkish descriptive oncological researches group
    (Asian Pacific Organization for Cancer Prevention, 2015) Tanriverdi O.; Avci N.; Oktay E.; Kalemci S.; Pilanci K.N.; Cokmert S.; Menekse S.; Kocar M.; Sen C.A.; Akman T.; Ordu C.; Goksel G.; Meydan N.; Barutca S.
    Background: Several prognostic factors have been studied in NSCLC, although it is unknown which is most useful. In this study, we aimed to investigate whether pre-treatment serum albumin level has prognostic value in patients with Stage IIIB NSCLC. Materials and Methods: This cross-sectional study included a total of 204 patients with Stage IIIB NSCLC who met the inclusion criteria. Pre-treatment serum albumin levels and demographic, clinical, and histological characteristics, as well as laboratory variables were recorded. A cut-off value was defined for serum albumin level and the patients were stratified into four groups on thios basis. Results: The majority of the patients was males and smokers, with a history of weight loss, and squamous histological type of lung cancer. The mean serum albumin level was 3.2±1.7 g/dL (range, 2.11-4.36 g/dL). A cut-off value 3.11 g/dL was set and among the patients with a lower level, 68% had adenocarcinoma and 82% were smokers. The patients with low serum albumin levels had a lower response rate to e first-line chemotherapy with a shorter progression-free survival and overall survival. Multivariate analysis showed that low serum albumin level was an independent poor prognostic factor for NSCLC. Conclusions: This study results suggest that low serum albumin level is an independent poor prognostic factor in patients with Stage IIIB NSCLC, associated with reduction in the response rate to first-line therapy and survival rates.
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    Efficacy and toxicity of cisplatin and capecitabine combination in the first-line treatment of patients with advanced gastric cancer: A multicenter study by the anatolian society of medical oncology; [İleri evre mide kanserli hastaların birinci basamak tedavisinde cisplatin ve kapesitabin kombinasyonunun etkinlik ve toksisitesi: Çok merkezli anadolu tıbbi onkoloji derneği çalışması]
    (UHOD - Uluslararasi Hematoloji Onkoloji Dergisi, 2016) Ciltas A.; Buyukberber S.; Topcu T.O.; Kucukoner M.; Uyeturk U.; Cihan S.; Sendur M.A.; Budakoglu B.; Kefeli U.; Yildiz R.; Goksel G.; Berk V.; Balakan O.; Oksuzoglu B.; Uncu D.; Coskun U.; Ozdemir F.; Benekli M.
    Gastric cancer is an important public health problem which comprises 10% of all cancers and 12% of all cancer related deaths all over the world. Because of the differences in patient populations and treatment schemes in various studies, standard practice for advanced stage gastric cancer has not been fully established. The aim of this study was to assess the use of cisplatin and capecitabine combination regimen in real-world clinical practice. Medical records of 76 male and 37 female metastatic gastric cancer patients treated with first-line cisplatin and capecitabine combination between February 2006 and December 2009 were retrospectively analyzed in 11 centers of the Anatolian Society of Medical Oncology. Patients previously treated with chemotherapy were excluded from the analysis. The median age of the patients was 64 years (range, 28-83). Seventy-six (67.2%) patients were males and 37 (32.7%) females. Most of the patients were metastatic (n= 85, 75.2%) at the time of initial diagnosis. The most common sites for metastasis were liver (65.9%), lung (11.3%), peritoneum (23.8%) and local recurrence (15.9%) with multiple metastases in 9.7% of the patients. The mean follow-up period of all patients was 41 months (range 12-61). Overall response rates was 33.6%, while disease control rate (DCR) was 72.6 %. Median Progression-free survival was 4.7 months (95%CI 3.75- 6.49) and median overall survival was 11.1 months (95%CI 5.58- 10.98). The most common grade 3-4 adverse events were anemia (8.3%), nausea-vomiting (3.8%) and diarrhea (1.8%). In terms of efficacy, toxicity and convenience, cisplatin and capecitabine combination is effective and well tolerated in Turkish patients with advanced gastric cancer, and could be one of the standard regimens for the first-line treatment in this cohort. © 2016, UHOD - Uluslararasi Hematoloji Onkoloji Dergisi. All rights reserved.
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    Role of increased mean platelet volume (MPV) and decreased MPV/platelet count ratio as poor prognostic factors in lung cancer
    (Blackwell Publishing Ltd, 2018) Omar M.; Tanriverdi O.; Cokmert S.; Oktay E.; Yersal O.; Pilancı K.N.; Menekse S.; Kocar M.; Sen C.A.; Ordu C.; Goksel G.; Meydan N.; Barutca S.
    Objectives: In this study, they investigated whether mean thrombocyte volume (MPV) and MPV/platelet count ratio have a prognostic significance in advanced NSCLC or not. Methods: A total of 496 NSCLC patients at stage IIIB/IV and did not meet exclusion criteria were included in the study. The demographic features (age, gender, smoking habit), clinical characteristics (performance status, weight loss, disease stage, first-line treatment regimen), laboratory tests (levels of hemoglobin, lactate dehydrogenase and calcium as well as MPV, MPV/platelet count ratio and counts of white blood cell, platelet), and histological features (histologic type, tumor grade) were recorded. Results: The MPV levels of all patients were determined as 10.2 {plus minus} 3.4 (range, 6.4-14.1 fL). With ROC curve analysis, the MPV/PC ratio was associated with a sensitivity of 67.8% and a specificity of 84.8% at a cutoff value of 0.47424 for presence of brain metastasis at the time of diagnosis. Univariate analysis showed that OS was significantly shorter in the group with an increased MPV level than in the other group (median OS time 6.8 months vs. 11.5 months, log-rank, P =.032). Multivariate analysis confirmed that an increased MPV level was an independent poor prognostic factor for OS (HR: 1.704, 95% CI: 1.274-3.415, P =.014). Conclusions: Unlike results of previous studies, the study showed that increased MPV was an important prognostic factor in patients with NSCLC. Hence, an increased MPV level may be used as a prognostic biomarker to estimate for poor overall survival in patients with NSCLC. © 2017 John Wiley & Sons Ltd