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Öğe Clinical Significance of Serum Insulin-Like Growth Factor-1 (Igf-1) and Insulinlike Growth Binding Protein-3 (Igfbp-3) in Patients With Gastric Cancer(CARBONE EDITORE, VIA QUINTINO SELLA, 68, PALERMO 90139, ITALY, 2018) Bademler, Süleyman; Sarı, Murat; Üçüncü, Muhammed Zübeyr; Serilmez, Murat; Karabulut, SenemIntroduction: Early diagnosis reduces mortality in gastric adenocarcinoma (GC). However, there are no markers that can be used to allow early diagnosis. The aim of the present study was to investigate clinical utility of insulin-like growth factor-1 (IGF-1) and insulin-like growth-binding protein-3 (IGFBP-3) in the diagnosis of GC. Materials and methods: Hundred and fifteen patients with histopathologically confirmed diagnosis of GC and 53 age- and sex-matched healthy controls were included in our study at Istanbul University Institute of Oncology. Serum IGF-1 and IGFBP-3 levels were determined using enzyme-linked immunosorbent assay (ELISA). Results: The mean age of the patients was 61 (range: 32-89) years. At the end of the median 11-month follow-up period, 75% (n=86) of the patients died. Serum IGF-1 and IGFBP-3 levels were significantly lower in the patient group than those in the control group (p=0.001). The sensitivity and specificity for IGF-1 were found to be 62.61% and 68.52%, respectively. The sensitivity and specificity for IGFBP-3 were found to be 73.91% and 62.96%, respectively. Serum IGFBP-3 levels were significantly higher in younger patients compared to those in older patients (p=0.009). The median survival was 14±3.3 months (95% CI=7.6- 20.4). 3-year survival rate was 25.6% (95% CI=15.4-35.8). Large T status, high N status and metastasis were found to have a prognostic role on survival (p=0.05, p=0.05, and p=0.003, respectively). Serum IGF-1 and IGFBP-3 concentrations had no prognostic role on survival (p=0.72, p=0.41, respectively). Conclusion: In our study, we showed that serum IGF-1 and IGFBP-3 levels could be used for early diagnosis of GC. We found that these two biomarkers have good sensitivity and specificity in clinical practice.Öğe Clinical Significance of Serum Membrane-Bound Mucin-2 Levels in Breast Cancer(MDPI, ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, 2019) Bademler, Süleyman; Zırtıloğlu, Alişan; Sarı, Murat; Üçüncü, Muhammed Zübeyr; Doğru, Elif Bilgin; Karabulut, SenemThis study was conducted to investigate the serum levels of membrane-bound mucin 2 (MUC2) in breast cancer (BC) patients and the relationship with tumour progression and known prognostic parameters. We enrolled 127 female patients with histopathologically diagnosed BC who did not receive chemotherapy (CT) or radiotherapy. Serum MUC2 levels were measured by the enzyme-linked immunosorbent assay (ELISA) method and compared with those of 40 age and sex-matched healthy controls. Median age of diagnosis was 50 (range: 26-78). Twenty-eight (22%) patients were metastatic and the most frequent site of metastasis was bone (n = 17, 61%). The median serum MUC2 level of BC patients was significantly higher than that of the controls (198 vs. 54 ng/mL, p < 0.001). There was no significant difference between patients and controls according to known disease-related clinicopathological or laboratory parameters (p > 0.05). Serum MUC2 levels were not associated with survival (p = 0.65). Although serum MUC2 levels might have a diagnostic role, their predictive and prognostic role in survival in BC patients was not detected. Serum levels of MUC2 should be investigated for diagnostic or screening purposes on a larger scale.Öğe Diagnostic and Prognostic Significance of Carboxypeptidase A4 (CPA4) in Breast Cancer(MDPI, ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, 2019) Bademler, Süleyman; Üçüncü, Muhammed Zübeyr; Tilgen Yasasever, Ceren; Serilmez, Murat; Ertin, Hakan; Karanlık, HasanRecent research focused on prolonged survival has suggested that carboxypeptidase A4 (CPA4) plays a role in both tumor microenvironment formation and distant metastasis in cancer. In some patients, serum and expression (mRNA) levels of CPA4 have been found to be correlated with the aggressiveness and progression of the disease. Accordingly, we conducted a first study to investigate the diagnostic and prognostic significance of CPA4 in the case of breast cancer (BC), the most common form of malignancy in women. The study included a total of 50 patients with BC and 20 healthy women as the control group. The participants' serum CPA4 levels were determined by the ELISA test, and, for assessment of CPA4 mRNA, we used the PCR method. The serum CPA4 (p = 0.001) and CPA4 mRNA (p = 0.015) levels were found to be statistically significantly higher in the controls, compared to the patient group. When the results of patient group were statistically analyzed based on subgrouping by tumor characteristics, the measured CPA4 mRNA levels showed significant difference with respect to the molecular subtype (p = 0.006), pN status (p = 0.023), and pathological stage (p = 0.039), while the serum CPA4 measurements differed significantly in terms of pathological type only (p = 0.024). We conclude that CPA4 is diagnostically and prognostically not futile when used in combination with the other considerations and measurements in breast cancer.Öğe The Diagnostic Significance of PDGF, EphA7, CCR5, and CCL5 Levels in Colorectal Cancer(MDPI, ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, 2019) Üçüncü, Muhammed Zübeyr; Serilmez, Murat; Sarı, Murat; Bademler, Süleyman; Karabulut, SenemIn this study, we compared the levels of C-C chemokine receptor type 5 (CCR5), C-C motif chemokine ligand 5 (CCL5), platelet-derived growth factor (PDGF), and EphrinA7 (EphA7) in patients with colorectal carcinoma and healthy controls in order to investigate the significance and usability of these potential biomarkers in early diagnosis of colorectal cancer. The study included 70 colorectal carcinoma patients and 40 healthy individuals. The CCR5, CCL5, PDGF, and EphA7 levels were measured using ELISA in blood samples. PDGF-BB, EphA7, CCR5, and CCL5 levels of the patients with colorectal carcinoma were significantly higher compared to the control group (p < 0.001 for each comparison). Our logistic regression analysis (the area under the curve was 0.958) supports the notion that PDGF-BB, EphA7, and CCL5 are potential biomarkers for the diagnosis of colon cancer. The sensitivity, specificity, and positive and negative predictive values were found to be 87.9%, 87.5%, 92.1%, and 81.4%, respectively. To our knowledge, this is the first study that investigates the relationship between colorectal carcinoma and the four biomarkers CCL5, CCR5, PDGF, and EphA7. The significantly elevated levels of all these parameters in the patient group compared to the healthy controls indicate that they can be used for the early diagnosis of colorectal carcinoma.Öğe An Investigation into the Role of IGF-1 and IGFBP3 in the Diagnosis and Treatment Response in Esophageal Cancer(İstanbul Gelişim Üniversitesi Yayınları / Istanbul Gelisim University Press, 2019) Bademler, Süleyman; Üçüncü, Merve Müge; Serilmez, MuratAim: Esophageal cancer (EC) is the eighth most common cancer among all cancers worldwide. It constitutes 1.5-2% of all cancers and 5-7% of gastrointestinal cancers. Mortality reduction by early diagnosis, early treatment, and close follow-up is possible in esophageal cancer. However, reliable markers that rapidly provide results for early diagnosis are necessary in order to make such a diagnosis. In our study, it is aimed to investigate the role of IGFBP3 and IGF-1 in the early diagnosis of esophageal tumors. Method: 37 patients with a histopathologically confirmed diagnosis of EC and 41 age- and sex-matched healthy controls were included in our study at Istanbul University Institute of Oncology. Serum IGF-1 and IGFBP-3 levels were determined using enzyme-linked immunosorbent assay (ELISA). Findings: The mean age of the patients included in this study was 54.51±13.69 years. Based on the comparison between the groups, there was no difference in terms of gender and age (p=0.675 and 0.094). There was a statistically significant difference between the control group and the patient group in terms of IGF-1 and IGFBP3 levels. Both levels were higher in the control group (p=0.006, p<0.001). 22 patients had a recurrence. There was no significant difference between the IGF and IGFBP3 levels in those who had a recurrence. 32 patients died. There was no significant difference in terms of the histological subtype, T and pathologic stage of the disease, and IGF-1 and IGFBP3 levels. Conclusion: Our study showed that IGF-1 and IGFBP3 markers could be used in the diagnosis of esophageal tumors. We think that it is necessary to conduct further studies with larger series in order to draw a clear conclusion.Öğe Kan Plazmasında Satellit-2 Tekrar Elementi DNA Dizilerinin Karakterizasyonu(İstanbul Gelişim Üniversitesi Yayınları / Istanbul Gelisim University Press, 2022) Özgür, Emre; Yıldız, Anıl; Bademler, Süleyman; Gezer, UğurAmaç: Son yıllarda tıp biliminin farklı disiplinlerinde sıkça karşılaşılan kavramlardan biri olan “sıvı biyopsi”, hastaların tanı, prognoz analizi ve tedaviye cevabını değerlendirme gibi konularda girişimsel doku biyopsisi yerine, kan ve çeşitli vücut sıvılarındaki moleküler ve epigenetik biyobelirteçlerin kullanılmasını içerir. Dolaşımda serbest halde dolaşan DNA’da (‘cell-free DNA’, cfDNA) kanser hücrelerine özgü gen mutasyonlarının saptanması, kanser hücrelerinin içeriğinin vücut sıvılarına geçtiğinin kesin kanıtı olarak kabul edilmektedir. cfDNA’nın bileşiminin belirlenmesine yönelik dizileme çalışmaları, perisentrik satellit DNA dizilerinin, cfDNA’da genom oranlarına kıyasla daha fazla oranda temsil edildiğini bildirmiştir. Bu çalışmada, kanser açısından spesifik dizilerin saptanması amacıyla, Sat-2 dizilerinin polimeraz zincir reaksiyonunda (PCR) çoğaltılmaları sonrasında daha detaylı karakterizasyonu amaçlanmıştır. Yöntem: Çalışmada, sağlıklı ve metastatik meme kanserli hastaların plazmalarından 1. ve 10. kromozoma spesifik Sat-2 dizileri PCR ile çoğaltıldıktan sonra, otomatik elektroforez sisteminde ayrıştırıldılar. Bulgular: Yapılan büyüklük analizinde, iki bölgeden çok sayıda amplikon oluştuğu, bunların yaklaşık %50’ni sırasıyla 143 ve 115 bç uzunluğunda ürünlerin oluşturduğu belirlenmiştir. Bu iki PCR amplikonunun miktarı meme kanserli hastalarda daha yüksek olarak hesaplandı. Onuncu kromozoma özgü 115 bç’lik fargman dışındaki Sat-2 dizileri açısından kontroller ile hastalar arasında önemli farklar olduğu belirlenmiştir. Sonuç: Çalışma kapsamında elde edilen bulgular, Sat-2 tekrar elementine ait DNA dizilerinin sekanslanması sonrası kansere spesifik hedef bölgelerin saptanabileceğini ortaya koymaktadır.Öğe Mide Kanseri Prognozunda Metastatik Lenf Nodu Oranı (Nratio) TNM Sınıflamasından Bağımsız Bir Parametredir(YERKURE TANITIM & YAYINCILIK HIZMETLERI A S, CUMHURYET CAD 48-3B, HARBIYE, ISTANB, 34367, TURKEY, 2019) Bademler, Süleyman; Üçüncü, Muhammed Zübeyr; Bulut, Türker; Asoğlu, OktarAmaç: Lenf nodu metastazının mide kanseri olgularında en önemli prognostik faktörlerden olduğu bilinmektedir. Farklı evrelendirme sınıflamalarında nodal tutulum, metastatik lenf nodlarının lokalizasyonu ve/veya sayısına göre değerlendirilmektedir. Ancak batılı ülkelerde mide kanseri olgularında uygulanan radikal rezeksiyonların sadece %30 kadarında değerlendirme için gereken en az 15 lenf nodu sayısına ulaşılabilmesi, aynı evrede yer alan hastalarda heterojen sürvilerin görülmesi ve evre kayması gibi sorunlar nedeni ile son yıllarda nodal değerlendirmede total pozitif nodu sayısı yerine metastatik lenf nodu oranının (N-Ratio) kullanılması önerilmektedir. Bu çalışmadaki temel amacımız mide kanseri olgularında prognostik parametrelerin retrospektif analizini yaparak 5 yıllık sağkalıma etkilerini incelemek ve özellikle N-Ratio’nun prognostik değerini araştırmaktır. Yöntemler: Ocak-2002 ve Aralık-2009 tarihleri arasında kliniğimizde mide kanseri tanısıyla küratif amaçlı cerrahi uygulanan 511 hastanın klinik kayıtları, patoloji ve ameliyat raporları retrospektif olarak incelendi. Sağkalım hesapları Kaplan-Meier yöntemi ile yapıldı. Mevcut prognostik faktörlerin 5 yıllık sağ kalım üzerine etkileri tek (Log Rank test) ve çok değişkenli (Cox regression) analizle araştırıldı. Sonuçlar %95’lik güven aralığında ve p<0,05 anlamlılık düzeyinde değerlendirildi. N-Ratio sınıflamasında, N0 (%0), N1 (%1-10), N2 (%11-25), N3 (%25-100) kesme değerleri olarak kullanıldı. Bulgular: Beş yıllık genel sağkalım oranları N0=%74,3, N1=% 66,3, N2=%59,8 N3=%30 olarak saptandı. N-Ratio oranlarına göre sağkalım oranları Log Rank test ile değerlendirildiğinde 5 yıllık sağ kalım oranları arasında istatistiksel olarak anlamlı farklılık saptandı (p<0,001). Bütün prognostik faktörlerin dahil edildiği çok değişkenli analiz (Cox regresyon modeli) sonucunda N-Ratio’nun radikal rezeksiyon uygulanmış mide kanseri hastalarının 5 yıllık genel sağkalımında pT ve N evresi ile birlikte etkili bağımsız bir prognostik faktör olduğu saptanmıştır (p<0,01). Tek değişkenli analizlerde 5 yıllık genel sağkalıma etki eden faktörler olan AJCC/UICC 6 ve 7. patolojik evre sınıflaması ve N-Ratio’nun dahil edildiği çok değişkenli istatistiksel analizlerde N-Ratio’nun sağkalıma etkili tek bağımsız prognostik faktör olduğu saptanmıştır (p=0,008). Sonuç: N-Ratio, lenf nodu metastazı olan mide kanseri olgularında basit, kullanışlı, efektif ve rasyonel bir prognostik göstergedir.Öğe Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer(KARE PUBL, CONCORD ISTANBUL, DUMLUPINAR MAH, CIHAN SK NO 15, B BLOK 162 KADIKOY, ISTANBUL 34720, TURKEY, 2021) Ak, Naziye; Serilmez, Murat; Üçüncü, Muhammed Zübeyr; Bademler, Süleyman; Vatansever, SezaiOBJECTIVE Evaluation of the nectin-2 and nectin-4 protein and mRNA expression levels is aimed in this study, with concerning diagnostic and predictive value in breast cancer patients. METHODS Sixty patients with pathologically and radiologically verified breast cancer who were treated at the Istanbul University, Institute of Oncology, between 2017 and 2018 are included in the study. Circulating nectin-2 and nectin-4 protein levels were evaluated by solid-phase enzyme-linked immunosorbent assay (Abbkine Scientific Co., Ltd.). For analyzing nectin-2- and nectin-4-specific mRNA in sera of the patients, circulating cell-free RNA was extracted from serum using a monophasic phenol and guanidine thiocyanate solution (Roche, Mannheim, Germany), according to the manufacturer’s protocol. RESULTS The median age of patients was 53 years. The mean tumor size was 30.21±17.32 mm. Forty-one patients were in the luminal group. Lymph node involvement was detected in 25 patients. The nectin-4 expression level was statistically significantly higher in those with Ki-67 ?30 and those with positive distant metastasis compared to the other group. In addition, nectin-2 expression was higher in patients with Grade 3 tumors. CONCLUSION High levels of nectin-2 and nectin-4 expression in the serum of patients correlate with poor disease characteristics of breast cancer.Öğe Our Therapeutic Approach to Idiopathic Granulomatous Mastitis(Hayat Sağlık ve Sosyal Hizmetler Vakfı, 2018-05-20) Bademler, Süleyman; Üçüncü, Muhammed ZübeyrAim: Granulomatous mastitis is a rare disease of the breast. Initial findings during admission can be mistaken for breast cancer. In this study, we aimed to present our experience with idiopathic granulomatous mastitis (IGM). Materials and Methods: Patients who had been treated and followed up after a diagnosis of GM at the surgical clinic of the Istanbul University Institute of Oncology between 2007 and 2017 were categorized into two groups: those who had received steroid treatment only (Group 1), and those who had received steroids in combination with surgical treatment (Group 2). The groups were compared in terms of clinical and demographic characteristics and recurrence rates. Findings: We included a total of seventy-nine patients in our study. The mean patient age was 36.41±6.93 years and the mean follow-up 57.34±20.39 months. There was no significant difference between the two groups in terms of mean age, age at menarche, maternal age at first delivery, and the side involved (right, left, bilateral). The disease had recurred in 19 patients in Group 1 while no recurrence had been observed in Group 2 (p=0.001). Discussion and Conclusion: IGM is a disease that is rare but easily mistakable for breast cancer. The diagnosis necessitates confirmation through a biopsy. Steroid therapy combined with surgery can be the first choice in the treatment of this disease, on which no consensus has yet been reached. Such combination is capable of reducing recurrence rates.Öğe Risk Factors for Complications in Cancer Patients with Totally Implantable Access Ports: A Retrospective Study and Review of the Literature(SAGE PUBLICATIONS LTD, 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND, 2019) Bademler, Süleyman; Üçüncü, Muhammed Zübeyr; Yıldırım, İlknur; Karanlık, HasanObjectives To analyze the risk factors for complications associated with the use of totally implantable access ports (TIAPs) in cancer patients. Methods Data for 2,713 cancer patients who received a TIAP between January 2010 and September 2016 at a single center were analyzed retrospectively. Results The average age of the patients was 54.2 +/- 9.92 years, and 1,247 (47.5%) were women. The right subclavian vein was the preferred insertion site. Seventy-seven patients developed early complications and 50 developed late complications. The incidence of complications increased as the number of punctures increased. Percutaneous intervention increased the risk of complications during port insertion, but age, sex, body mass index, and the use of physiological saline solution instead of heparin for washing after port insertion did not increase the risk. The use of ultrasonography during insertion reduced the risk of complications. Conclusions Various factors may affect the function of TIAPs in cancer patients both during insertion and follow-up. Age, sex, body mass index, and the use of physiological saline solution for washing did not affect the incidence of complications, but the use of ultrasonography during insertion did affect the complication rate.Öğe The Diagnostic Value of circFBXW7, circABCB10, and circ0103552 Levels in Breast Cancer(MDPI, ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, 2024) İlhan, Burak; Ender, Şenol; Kılıç, Berkay; Üçüncü, Muhammed; Serilmez, Murat; Yasasever, Ceren Tilgen; Soydinç, Hilal Oğuz; Kuras, Sibel; Erdoğan, Bekir; Alsaadoni, Hani; Karanlık, Hasan; Bademler, SüleymanDespite advances in cancer treatment, breast cancer (BC) remains one of the most common cancers affecting women worldwide. This study aimed to determine serum circFBXW7, circABCB10, and circ0103552 levels and compare BC patients and healthy controls to investigate their roles in the molecular mechanism of BC and the significance of these circRNAs in BC diagnosis. The study group consisted of 92 patients with BC and 31 healthy controls. Total RNA was isolated from serum samples. Following total RNA, complementary DNA was synthesized from this material. Following complementary DNA analysis, the circRNA levels were analyzed by the qRT-PCR method. Expression levels were evaluated in ∆Ct values. High ∆Ct values of circFBXW7 and circ0103552 and low ∆Ct values of circABCB10 were correlated with BC diagnosis (circFBXW7, p = 0.043, r = 0.183, circ0103552, p < 0.001, r = 0.321, circABCB10, p = 0.001, r = −0.291). According to Fold Change (FC) values, circFBXW7 (FC = 0.30) and circ0103552 (FC = 0.26) showed low expression in the patient group compared to the control group, while circABCB10 (FC = 11.09) showed high expression (p < 0.05, for all comparisons). We think that our study is one of the rare studies investigating the relationship between BC and serum circRNA levels. This study concludes that the significant downregulation of circFBXW7 and circ0103552 and the upregulation of circABCB10 are directly related to the diagnosis of BC and can be used for diagnosis, but further studies are needed to elucidate the molecular mechanism of the relationship between circRNAs and BC.Öğe The Role of Biomarkers in the Early Diagnosis of Gastric Cancer: A Study on CCR5, CCL5, PDGF, and EphA7(MDPI, ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, 2024) Bademler, Süleyman; Kılıç, Berkay; Üçüncü, Muhammed Zübeyr; Zırtıloğlu, Alişan; İlhan, BurakDespite the use of screening programs, gastric cancer (GC) diagnosis may only be possible at an advanced stage. In this study, we examined the serum levels of C-C chemokine receptor type 5 (CCR5), C-C motif chemokine ligand 5 (CCL5), platelet-derived growth factor (PDGF), and EphrinA7 (EphA7) in patients with gastric carcinoma and healthy controls to investigate the significance and usability of these potential biomarkers in the early diagnosis of GC. The study enrolled 69 GC patients and 40 healthy individuals. CCR5, CCL5, PDGF-BB, and EphA7 levels, which have been identified in the carcinogenesis of many cancers, were measured in the blood samples using the ELISA method. CCR5, CCL5, PDGF-BB, and EphA7 were all correlated with GC diagnosis (CCR5, p < 0.001, r = −0.449; CCL5, p = 0.014, r = −0.234; PDGF-BB, p < 0.001, r = −0.700; EPHA7, p < 0.001, r = −0.617). The serum CCR5, EphA7, and especially the PDGF-BB levels of the patients diagnosed with GC were discovered to be significantly higher compared to the healthy controls. PDGF-BB had the highest positive and negative predictive values when evaluated in ROC analysis to determine its diagnostic significance (cut-off value: 59.8 ng/L; AUC: 0.92 (0.87–0.97)). As far as we know, this is the first study to investigate the potential connection between GC and these four biomarkers. The fact that serum CCR5, CCL5, EphA7, and especially PDGF-BB levels in the patient group were significantly higher compared to healthy controls indicates that they can be used with high accuracy in the early diagnosis of GC. In addition, the levels of CCR5, PDGF-BB, and EphA7 can be used as important indicators to predict the biological behavior and prognosis of GC.
