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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/3
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Publication Metadata only Investigation of ionizing radiation response in new resistance models of glioblastoma.(Amer Assoc Cancer Research, 2021) N/A; N/A; Değirmenci, Nareg Pınarbaşı; Önder, Tuğba Bağcı; Sur, İlknur Erdem; Selek, Uğur; PhD Student; Faculty Member; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; School of Medicine; School of Medicine; N/A; 184359; N/A; 27211N/APublication Metadata only Malignancy and lymphoid proliferation in primary immune deficiencies; hard to define, hard to treat(Wiley, 2020) Kiykim, Ayca; Eker, Nursah; Surekli, Ozlem; Nain, Ercan; Kasap, Nurhan; Dogru, Omer; Canbolat, Aylin; Somer, Ayper; Koc, Ahmet; Tokuc, Gulnur; Bozkurt, Suheyla; Turkoz, Kemal; Karakoc-Aydiner, Elif; Ozen, Ahmet; Baris, Safa; Aktürk, Hacer; Faculty Member; School of Medicine; 162936Background Regarding the difficulties in recognition and management of the malignancies in primary immune deficiencies (PIDs), we aimed to present the types, risk factors, treatment options, and prognosis of the cancers in this specific group. Methods Seventeen patients with PID who developed malignancies or malignant-like diseases were evaluated for demographics, clinical features, treatment, toxicity, and prognosis. Results The median age of malignancy was 12.2 years (range, 2.2-26). Lymphoma was the most frequent malignancy (n = 7), followed by adenocarcinoma (n = 3), squamous cell carcinoma (n = 2), cholangiocarcinoma (n = 1), Wilms tumor (n = 1), and acute myeloid leukemia (n = 1). Nonneoplastic lymphoproliferation mimicking lymphoma was observed in five patients. The total overall survival (OS) was 62.5% +/- 12.1%. The OS for lymphoma was 62.2% +/- 17.1% and found to be inferior to non-PID patients with lymphoma (P = 0.001). Conclusion In patients with PIDs, malignancy may occur and negatively affect the OS. The diagnosis can be challenging in the presence of nonneoplastic lymphoproliferative disease or bone marrow abnormalities. Awareness of susceptibility to malignant transformation and early diagnosis with multidisciplinary approach can save the patients' lives.Publication Metadata only Diagnostic accuracy of sentinel node biopsy in non-endometrioid, high-grade and/or deep myoinvasive endometrial cancer: a Turkish gynecologic oncology group study (TRSGO-SLN-006)(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2022) Altın, Duygu; Taşkın, Salih; Ortaç, Firat; Tokgözoğlu, Nedim; Güler, Abdul Hamid; Güngör, Mete; Taşcı, Tolga; Bese, Tugan; Turan, Hasan; Kahramanogğu, İlker; Yalçın, İbrahim; Çelik, Çetin; Demirkıran, Fuat; Köse, Faruk; Arvas, Macit; Ayhan, Ali; Vatansever, Doğan; Taşkıran, Çağatay; Faculty Member; Faculty Member; School of Medicine; School of Medicine; 193687; 134190Introduction: This study aimed to evaluate the diagnostic accuracy of the sentinel lymph node (SLN) mapping algorithm in high-risk endometrial cancer patients. Methods: Two hundred forty-four patients with non-endometrioid histology, grade 3 endometrioid tumors and/or tumors with deep myometrial invasion were enrolled in this retrospective, multicentric study. After removal of SLNs, all patients underwent pelvic +/- paraaortic lymphadenectomy. Operations were performed via laparotomy, laparoscopy or robotic surgery. Indocyanine green (ICG) and methylene blue (MB) were used as tracers. SLN detection rate, sensitivity, negative predictive value (NPV) and false-negative rate (FNR) were calculated. Results: Surgeries were performed via laparotomy in 132 (54.1%) patients and 152 (62.3%) underwent both bilateral pelvic and paraaortic lymphadenectomy. At least 1 SLN was detected in 222 (91%) patients. Fifty-five (225%) patients had lymphatic metastasis and 45 patients had at least 1 metastatic SLN. Lymphatic metastases were detected by side-specific lymphadenectomy in 8 patients and 2 patients had isolated paraaortic metastasis. Overall sensitivity, NPV and FNR of SLN biopsy were 81.8%, 95% and 182%, respectively. By applying SLN algorithm steps, sensitivity and NPV improved to 96.4% and 98.9%, respectively. For grade 3 tumors, sensitivity, NPV and FNR of the SLN algorithm were 97.1%, 98.9% and 2.9%. Conclusion: SLN algorithm had high diagnostic accuracy in high-risk endometrial cancer. All pelvic metastases were detected by the SLN algorithm and the isolated paraaortic metastasis rate was ignorable. But long-term survival studies are necessary before this approach becomes standard of care.Publication Metadata only The role of adjuvant chemotherapy in resected stage I non - small cell lung cancer: a Turkish Oncology Group Study(Imprimatur Publications, 2021) Ak, Naziye; Özkan, Berker; Yenigün, Mustafa B.; Yılmazbayhan, Dilek; Toker, Alper; Ferhatoğlu, Ferhat; Yaşar, Arzu; Sak, Serpil Dizbay; Kılıçkap, Sadettin; Önder, Sevgen; Dikmen, Erkan; Alan, Özkan; Yumuk, Perran F.; Bozkurtlar, Emine; Laçin, Tunç; Yıldızeli, Bedrettin; Özturk, Akın; Ürer, Nur; Oyan, Başak; Aydıner, Adnan; Demirkazık, Ahmet; Eralp, Yeşim; Kocatürk, Celalettin; Karapınar, Kemal; Tanju, Serhan; Dilege, Şükrü; Erus, Suat; Bulutay, Pınar; Fırat, Pınar Arıkan; Mandel, Nil Molinas; Faculty Member; Faculty Member; Faculty Member; Teaching Faculty; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; 214690; 122573; 175565; 133565; 207545; 194197Purpose: The benefit of adjuvant chemotherapy for tumors smaller than 4 cm is not clear. We aimed to evaluate the prognostic impact of adjuvant platin-based chemotherapy in high-risk stage I patients with non-small cell lung cancer (NSCLC). Methods: This cooperative group study included 232 NSCLC patients who underwent curative surgery for stage I disease with tumor size 2-4 cm. Results: Median age at presentation was 63 years (range 18-90). The mean tumor size was 29.6 +/- 7.3 mm. The frequency of patients with specified risk factors were: visceral pleural effusion (VPI): n: 82 (36.6%); lymphovascular invasion (LVI): n: 86 (39.1%); Grade 3: n: 48 (32.7%); Solid micropapillary pattern (SMP): n: 70 (48.3%). Adjuvant platin-based chemotherapy was administered to 51 patients. During a median follow-up period of 50.5 months 68 patients (29.3%) developed recurrence, 54 (23.3%) died from any cause and 38 (16.4%) of them died of lung cancer. Patients who received chemotherapy compared with the non-chemotherapy group had a longer 5-years relapse-free survival (RFS) (84.5 vs. 61.1%). Also on multivariate analysis, adjuvant chemotherapy was a significant independent prognostic factor for RFS. Conclusion: Adjuvant platin-based chemotherapy should be considered for patients with small tumors with adverse risk factors.Publication Metadata only From probands to relatives(Lippincott Williams and Wilkins (LWW), 2022) Shah, Lisa L.; Yazici, Hulya; Daack-Hirsch, Sandra; N/A; Seven, Memnun; Faculty Member; School of Nursing; 32470Background The genetic risk communication from proband to relatives varies from family to family, and patients often need support with the communication of genetic test results and making decisions to manage hereditary cancer risks. Objective The aim of this study was to characterize the communication of BRCA1 or BRCA2 (BRCA1/2) genetic risk from proband to first-degree relatives (FDRs) using a social network framework. Methods We characterized network and nonnetwork factors to explore their association with which FDRs were told about the genetic risk and whether or not relatives underwent genetic testing. Ninety-two female probands with hereditary breast and ovarian cancer who have confirmed BRCA1/2 mutations participated in the study. Communication of hereditary breast and ovarian cancer risk was assessed between 92 probands and their 417 FDRs. Results of 92 probands, 94.5% (n = 87) communicated their genetic test result to at least one of their FDRs. of FDRs older than 18 years, 19.9% (n = 72) have genetic testing. Emotional closeness, educational level of the proband, and relative's age were significantly associated with communicating test results with FDRs. Conclusion Communication of genetic risk with the FDRs after having a BRCA1/2 gene-mutation-positive test result was high in this group of cancer patients. However, the rate of genetic testing among FDRs was low. Implications for Practice Probands' educational level and age of relatives for cascade genetic screening should be considered during counseling. Interventions to support women with BRCA1/2 mutations during the communication process and their family members' engagement in testing and risk-reducing strategies are needed.Publication Metadata only Dual LSD1 and HDAC6 inhibition induces doxorubicin sensitivity in acute Myeloid Leukemia cells(MDPI, 2022) Lee, Adam; Cevatemre, Buse; Ruzic, Dusan; Belle, Roman; Kawamura, Akane; Gul, Sheraz; Nikolic, Katarina; Ganesan, A.; Acilan, Ceyda; Bulut, İpek; PhD Student; Graduate School of Health Sciences; N/ASimple Summary GSK2879552 is a LSD1 inhibitor in clinical development. By structural modification, we obtained an analogue that is a potent and selective dual inhibitor of HDAC6 and LSD1 (IC50 110 and 540 nM, respectively). The dual targeting agent was superior to GSK2879552 in the growth inhibition of two acute myeloid leukemia (AML) cell lines. In combination experiments, the dual inhibitor primed AML cells to apoptosis with a sublethal concentration of doxorubicin. Our data suggest that doxorubicin toxicity can be reduced by parallel inhibition of HDAC6 and LSD1. Defects in epigenetic pathways are key drivers of oncogenic cell proliferation. We developed a LSD1/HDAC6 multitargeting inhibitor (iDual), a hydroxamic acid analogue of the clinical candidate LSD1 inhibitor GSK2879552. iDual inhibits both targets with IC50 values of 540, 110, and 290 nM, respectively, against LSD1, HDAC6, and HDAC8. We compared its activity to structurally similar control probes that act by HDAC or LSD1 inhibition alone, as well as an inactive null compound. iDual inhibited the growth of leukemia cell lines at a higher level than GSK2879552 with micromolar IC50 values. Dual engagement with LSD1 and HDAC6 was supported by dose dependent increases in substrate levels, biomarkers, and cellular thermal shift assay. Both histone methylation and acetylation of tubulin were increased, while acetylated histone levels were only mildly affected, indicating selectivity for HDAC6. Downstream gene expression (CD11b, CD86, p21) was also elevated in response to iDual treatment. Remarkably, iDual synergized with doxorubicin, triggering significant levels of apoptosis with a sublethal concentration of the drug. While mechanistic studies did not reveal changes in DNA repair or drug efflux pathways, the expression of AGPAT9, ALOX5, BTG1, HIPK2, IFI44L, and LRP1, previously implicated in doxorubicin sensitivity, was significantly elevated.Publication Metadata only The effect of the time interval between temozolomide and radiotherapy in adjuvant high-grade glioma treatment(Elsevier, 2022) Oymak, E.; Demircan, V.; Yavas, G.; Guler, O. C.; Erpolat, P.; Onal, C.; N/A; Bölükbaşı, Yasemin; Şenyürek, Şükran; Faculty Member; Doctor; School of Medicine; N/A; 216814; N/AN/APublication Metadata only How i treat relapsed classical hodgkin lymphoma after autologous stem cell transplantation(Pergamon-Elsevier Science Ltd, 2016) N/A; Akay, Olga Meltem; Faculty Member; School of Medicine; 170966N/APublication Metadata only Safety of combined immunotherapy and thoracic radiation therapy: analysis of 3 single-institutional phase I/II trials(Elsevier Science Inc, 2018) Verma, Vivek; Cushman, Taylor R.; Tang, Chad; Welsh, James W.; Selek, Uğur; Faculty Member; School of Medicine; 27211Purpose: The safety of combined immunotherapy and thoracic radiation therapy (iRT) has been understudied. We evaluated toxicities in patients receiving iRT from 3 single-institutional phase 1/2 trials. Methods and Materials: Clinical/treatment characteristics and toxicities (per the Common Toxicity Criteria for Adverse Events, version 4.0) were extracted. For purposes of this analysis, groupings were made into (1) patients receiving immunotherapy plus stereotactic body radiation therapy (50 Gy/4 fractions or 60 Gy/10 fractions), (2) immunotherapy plus 45 Gy/15 fractions, and (3) twice-daily chemoimmunoradiotherapy (45 Gy in twice-daily fractions). Results: None of the 60 patients undergoing immunotherapy plus stereotactic body radiation therapy (50 Gy, n = 49; 60 Gy, n = 11) experienced grade >= 4 events. There were 34 instances of any grade 3 event (in 15 total patients), with 9 pulmonary specific grade 3 events (in 4 patients). In the patients receiving 45 Gy/15 fractions (small cell lung cancers, n = 26; non-small cell lung cancers, n = 27), there were 2 grade 4 events (in the same patient), along with 17 grade 3 toxicities experienced by 10 total patients (2 pulmonary specific). Lastly, in the twice-daily cohort (n = 22), there were 5 grade 4 events (3 of which occurred in 1 patient) and 16 grade 3 toxicities occurring in 8 total patients (half of which were hematologic). Conclusions: Administration of combined iRT is safe in the short term. Toxicities did not appreciably associate with demographics or dosimetry.Publication Metadata only Deep cervical injection: a novel technique to increase bilateral sentinel lymph node detection rate in endometrial cancer patients with indocyanine green (TRSGO-SLN-008)(BMJ Publishing Group, 2022) Altin, Duygu; Taskin, Salih; Tokgozoglu, Nedim; Guler, Abdul Hamid; Tasci, Tolga; Bese, Tugan; Turan, Hasan; Kahramanoglu, Ilker; Yalcin, Ibrahim; Celik, Cetin; Demirkiran, Fuat; Gungor, Mete; Ortac, Firat; Kose, Faruk; Arvas, Macit; Ayhan, Ali; N/A; Taşkıran, Çağatay; Vatansever, Doğan; Giray, Burak; Dönmez, Emin Erhan; Faculty Member; Faculty Member; Faculty Member; Researcher; School of Medicine; School of Medicine; School of Medicine; School of Medicine; 134190; 193687; 316087; 334646Objectives: Lymph node assessment provides information that may influence decisions regarding adjuvant treatment in endometrial cancer patients. However, systematic lymphadenectomy may cause significant morbidity. In recent years, the use of sentinel lymph node (SLN) mapping with indocyanine green (ICG) has been accepted to avoid the morbidity of lymphadenectomy. We aimed to assess the diagnostic accuracy of a novel injection technique in detection of sentinel lymph nodes in women with endometrial cancer. Methods: A total of 214 patients with endometrial cancer underwent sentinel lymph node mapping using ICG. ICG was injected into the uterine cervix at the 3 and 9 o’clock positions, submucosally and to the level of junction between uterine cervix and isthmus in group 1(n=107) and to the uterine cervix at the 3 and 9 o’clock positions according to conventional Memorial Sloan Kettering algorithm in group 2(n=107). All the patients in group 2 selected by propensity matching. None of the patients underwent a re-injection neither in group 1 nor group 2. Results: There was no significant difference between baseline characteristics of two groups. The groups were similar in terms of stage, type of tumor, BMI and lymphovascular space invasion. The bilateral detection rates were 94.4% and 76.6% in group 1 and group 2, respectively (p=0.003). No lymph node or lymphatic vessels were identified in only one patient with a history of chronic lymphocytic leukemia in group 1. Conclusions: Deep cervical injection technique significantly increases bilateral SLN detection rate in endometrial cancer patients.