Browsing by Author "Keskin, Selcuk"

Now showing 1 - 5 of 5

5-Hydroxyuracil Incision Activity Varies According to the Histological Grade of Non-muscle-invasive Bladder Cancer
(GALENOS YAYINCILIK, 2021-01-01) Keskin, Selcuk; Antmen, Fatma Merve; Somuncu, Berna; Saglican, Yesim; Doganca, Tunkut; Obek, Can; Ince, Umit; Kural, Ali Riza; Muftuoglu, Meltem
Objective: High levels of endonuclease III-like 1 (NTHL1) DNA glycosylase, which plays a role in the first step of the base excision repair pathway, has been related to cancer initiation and progression. 5-hydroxyuracil (5-OHU) oxidative base damage is a substrate for NTHL1 and endonuclease VIII-like 1 enzyme 1 (NEIL1) DNA glycosylases. This study investigates the association of 5-OHU incision activity with the risk of disease progression in patients with non-muscle-invasive bladder cancer (NMIBC) regarding grade and stage. Materials and Methods: During transurethral resection of 17 NMIBC patients, the papillary tumour before monopolar resection and healthy bladder mucosal tissue from the same person were obtained using cold cup biopsy. Both the normal mucosa and NMIBC tumour were pathologically confirmed. The histological grade and stage were also determined. The 5-OHU incision activity of all tissues was measured using a radiolabelled 5-OHU modified base containing DNA substrate. Results: 5-OHU incision activity was significantly higher in all high-grade NMIBC tissue extracts compared with the corresponding normal tissues (p=0.001). However, we found no significant difference in 5-OHU incision activity in low-grade NMIBC tissues (p=0.89). There was also a significant increase in 5-OHU incision activity at the Ta/T1 stage compared with the corresponding normal tissue (p=0.001). Conclusion: The increase in 5-OHU incision activity according to the histological grade of NMIBC tissue indicates that this activity (mainly performed by NTHL1 and NEIL1 DNA glycosylases) might play a role in NMIBC prognosis. Thus, it could be used as a potential prognostic biomarker for NMIBC.
Bacillus Calmette-Guerin Increases Base Excision Repair in Bladder Cancer Cells
(GALENOS YAYINCILIK, 2021-01-01) Keskin, Selcuk; Somuncu, Berna; Muftuoglu, Meltem
Objective: Most patients with non-muscle-invasive bladder cancer (NMIBC) do not respond to intravesical Bacillus Calmette-Guerin (BCG) immunotherapy and have high risk of NMIBC recurrence and progression. In addition to its therapeutic effect which increases the local immune response, BCG also exerts an anti-tumour effect by increasing oxidative stress, and producing reactive oxygen species and oxidative DNA damage in bladder cancer (BC) cells. The oxidative DNA damage is repaired by base excision repair (BER) mechanism. Thus, BER capacity of BC cells could be an important factor in response to BCG therapy. Effects of BCG on the activity of BER in BC transitional carcinoma cell line, T24 have been investigated. Materials and Methods: The uracil-initiated total BER and BER enzyme activities were measured in whole cell extracts with or without BCG treatment using a {[}gamma-32P] adenosine triphosphate-labelled 51-mer DNA substrates. Results: BCG treatment increased the activities of uracil-initiated total BER and BER enzymes, uracil DNA glycosylase and DNA polymerase beta in 6 h and 24 h repair periods and increased the activity of 8-oxoguanine DNA glycosylase in 6 h repair in T24 BC cell line. Conclusion: The enhanced BER activity in BC cells in response to BCG treatment could be an important factor in BCG resistance.
Minimizing Ports During Robotic Partial Nephrectomy
(SOC LAPAROENDOSCOPIC SURGEONS, 2016-01-01) Argun, Omer Burak; Mourmouris, Panagiotis; Tufek, Ilter; Obek, Can; Tuna, Mustafa Bilal; Keskin, Selcuk; Kural, Ali Riza
Background and Objective: Robotic upper urinary tract surgery is in most of the cases performed utilizing a standard 5 port configuration. Fewer ports can potentially produce a less invasive operation. Taking in consideration the above we report a novel technique for robot assisted laparoscopic partial nephrectomy utilizing fewer ports and we test its feasibility and safety profile. Methods: Data on 11 robot-assisted laparoscopic partial nephrectomies performed by using our technique from February 2015 through June 2015 were retrospectively analyzed. The robotic platform used was DaVinci Xi (Intuitive Surgical, Inc., Sunnyvale, California, USA) with a 3-arm setup. The AirSeal system (SurgiQuest, Milford, Connecticut, USA) was used as a port allowing simultaneous introduction of 2 instruments for the bedside surgeon, obviating the need for an additional (fourth) robotic arm. A long suction-and-irrigation device and atraumatic grasping forceps were used. Both instruments were introduced through the trocar of the AirSeal system, making simultaneous introduction and use possible. We preferred the long suction-and-irrigation device, because it minimizes collision of the instruments. Results: Mean age and BMI of the patients were 55 +/- 14.6 y and 29.18 +/- 6.85, respectively. Seven tumors were on the right side and 4 were on the left. The mean size of the tumors was 32.45 mm (+/- 11.31). Surgical time was 132.2 minutes (+/- 37.17), with an estimated blood loss and ischemia time of 103.63 mL (+/- 65.92) and 16.72 minutes (+/- 9.52), respectively. One patient had postoperative bleeding that was resolved without transfusion. The median hospitalization period was 3.9 d (+/- 0.53). Loss of intra-abdominal pressure was not observed, and pressure was stable at 10 mm Hg. Conclusion: The AirSeal System and its valveless trocar eliminated the need for an additional port placement in our series. The technique is feasible, safe, and reproducible
Non-muscle invasive bladder cancer tissues have increased base excision repair capacity
(NATURE PORTFOLIO, 2020-01-01) Somuncu, Berna; Keskin, Selcuk; Antmen, Fatma Merve; Saglican, Yesim; Ekmekcioglu, Aysegul; Ertuzun, Tugce; Tuna, Mustafa Bilal; Obek, Can; Wilson, David M.; Ince, Umit; Kural, Ali Riza; Muftuoglu, Meltem
The molecular mechanisms underlying the development and progression of bladder cancer (BC) are complex and have not been fully elucidated. Alterations in base excision repair (BER) capacity, one of several DNA repair mechanisms assigned to preserving genome integrity, have been reported to influence cancer susceptibility, recurrence, and progression, as well as responses to chemotherapy and radiotherapy. We report herein that non-muscle invasive BC (NMIBC) tissues exhibit increased uracil incision, abasic endonuclease and gap-filling activities, as well as total BER capacity in comparison to normal bladder tissue from the same patient (p<0.05). No significant difference was detected in 8-oxoG incision activity between cancer and normal tissues. NMIBC tissues have elevated protein levels of uracil DNA glycosylase, 8-oxoguanine DNA glycosylase, AP endonuclease 1 and DNA polymerase beta protein. Moreover, the fold increase in total BER and the individual BER enzyme activities were greater in high-grade tissues than in low-grade NMIBC tissues. These findings suggest that enhanced BER activity may play a role in the etiology of NMIBC and that BER proteins could serve as biomarkers in disease prognosis, progression or response to genotoxic therapeutics, such as Bacillus Calmette-Guerin.
Presentation and prognosis of female acute urinary retention: Analysis of an unusual clinical condition in outpatients
(MEDKNOW PUBLICATIONS \& MEDIA PVT LTD, 2016-01-01) Ozveren, Bora; Keskin, Selcuk
Objectives: Acute urinary retention (AUR) in females is a poorly defined condition with undetermined epidemiology. This study aimed to evaluate female AUR in an outpatient population. Patients and Methods: One hundred and thirty-eight adult female outpatients who presented to the emergency room with symptoms of urinary retention were retrospectively analyzed. The women who were ultimately diagnosed with true, complete AUR were systematically reviewed for clinical characteristics and management. Results: In this outpatient cohort with urinary retention complaints, only 23\% of the patients were diagnosed with objective AUR. Detailed medical and urological history in addition to urogenital, neurological, and pelvic examinations was essential