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Publication Open Access #COVID19 and #Breastcancer: a qualitative analysis of tweets(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Naganathan, G.; Cleland, J.; Reel, E.; Cil, T.; Bilgen, İdil; School of MedicineRapid and efficient communication regarding quickly evolving medical information was paramount for healthcare providers and patients throughout the COVID-19 pandemic. Over the last several years, social media platforms such as Twitter have emerged as important tools for health promotion, virtual learning among healthcare providers, and patient support. We conducted a qualitative thematic content analysis on tweets using the hashtags #BreastSurgery, #BreastCancer, #BreastOncology, #Pandemic, and #COVID19. Advocacy organizations were the most frequent authors of tweets captured in this dataset, and most tweets came from the United States of America (64%). Seventy-three codes were generated from the data, and, through iterative, inductive analysis, three major themes were developed: patient hesitancy and vulnerability, increased efforts in knowledge sharing, and evolving best practices. We found that Twitter was an effective way to share evolving best practices, education, and collective experiences among key stakeholders. As Twitter is increasingly used as a tool for health promotion and knowledge translation, a better understanding of how key stakeholders engage with healthcare-related topics on the platform can help optimize the use of this powerful tool.Publication Open Access Activated leukocyte cell adhesion molecule regulates the interaction between pancreatic cancer cells and stellate cells(Spandidos Publications, 2016) Zhang, Wei-Wei; Zhan, Shu-Hui; Geng, Chang-Xin; Sun, Xin; Kleeff, Joerg; Xie, Xiang-Jun; N/A; Erkan, Murat Mert; Faculty Member; School of Medicine; 214689Activated leukocyte cell adhesion molecule (ALCAM/CD166) is a transmembrane glycoprotein that is involved in tumor progression and metastasis. In the present study, the expression and functional role of ALCAM in pancreatic cancer cells and pancreatic stellate cells (PSCs) was investigated. Tissue specimens were obtained from patients with pancreatic ductal adenocarcinoma (n=56) or chronic pancreatitis (CP; n=10), who underwent pancreatic resection, and from normal pancreatic tissue samples (n=10). Immunohistochemistry was used to analyze the localization and expression of ALCAM in pancreatic tissues. Subsequently, reverse transcription-quantitative polymerase chain reaction and immunoblotting were applied to assess the expression of ALCAM in pancreatic cancer Panc-1 and T3M4 cells, as well as in PSCs. An enzyme-linked immunosorbent assay was used to measure ALCAM levels in cell culture medium stimulated by hypoxia, tumor necrosis factor (TNF)- and transforming growth factor-. Silencing of ALCAM was performed using ALCAM small interfering (si)RNA and immunocytochemistry was used to analyze the inhibition efficiency. An invasion assay and a cell interaction assay were performed to assess the invasive ability and co-cultured adhesive potential of Panc-1 and T3M4 cells, as well as PSCs. Histologically, ALCAM expression was generally weak or absent in pancreatic cancer cells, but was markedly upregulated in PSCs in pancreatic cancer tissues. ALCAM was highly expressed in PSCs from CP tissues and PSCs surrounding pancreatic intraepithelial neoplasias, as well as in pancreatic cancer cells. ALCAM mRNA was highly expressed in PSCs, with a low to moderate expression in T3M4 and Panc-1 cells. Similar to the mRNA expression, immunoblotting demonstrated that ALCAM protein levels were high in PSCs and T3M4 cells, but low in Panc-1 cells. The expression of TNF- increased, while hypoxia decreased the secretion of ALCAM in pancreatic cancer Panc-1 and T3M4 cells, and also in PSCs. Silencing of ALCAM by siRNA revealed no significant alteration in the invasion of pancreatic cancer cells, however, it inhibited the invasive ability of PSCs, and decreased the interaction between Panc-1 cells and PSCs. In conclusion, ALCAM is upregulated in PSCs of pancreatic cancer tissues, suggesting a potential role of ALCAM in regulating pancreatic cancer cell-PSC interactions.Publication Open Access Adjuvant chemotherapy for gastric cancer in elderly patients has same benefits as in younger patients(Medknow Publications, 2018) Karaca, Mustafa; Tural, Deniz; Koçoğlu, Hakan; Bilgetekin, İrem; Özet, Ahmet; N/A; Selçukbiricik, Fatih; Faculty Member; School of MedicineObjective: The age-adjusted mortality rate due to gastric cancer was reported to increase with age. This study aims to investigate the results of adjuvant chemotherapy in patients aged 65 years or older comparing with younger patients and focusing on its impact on survival. Materials and Methods: A total of 406 patients with nonmetastatic gastric cancer that consisted of 283 patients younger than 65 years (range: 23-64 years) and 123 patients 65 years of age or older (range: 65-75 years) were retrospectively evaluated. Categorical and continuous variables were summarized using the descriptive statistics and compared with Chi-square and Mann-Whitney U-tests, respectively. Cancer-specific survival rates were estimated by the Kaplan-Meier method. Results: Median age at diagnosis was 58 years (range: 23-75 years). There was no significant difference in gender, tumor localization in the stomach (cardia/noncardia), tumor histology, perineural invasion, lymphovascular invasion, histopathological characteristics of the tumor, and tumor stage between groups. No significant difference was detected in survival between groups. The median survivals were 20.8 months (range: 17-24.6) in patients younger than 65 years and 19.5 months (range: 14.8-24.1) in patients 65 years of age or older (P = 0.9). Conclusions: We showed that adjuvant chemotherapy in elderly patients with gastric cancer has same effectiveness as nonelderly patients. However, further well-designated prospective studies are needed to confirm these findings.Publication Open Access Assessment of health-related quality of life in patients with advanced prostate cancer current state and future perspectives(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Kretschmer, A.; Van Den Bergh, R.C.N., Martini, A.; Marra, G.; Valerio, M.; Tsaur, I.; Heidegger, I.; Kasivisvanathan, V.; Kesch, C.; Preisser, F.; Fankhauser, C.D.; Zattoni, F.; Ceci, F.; Olivier, J.; Chiu, P.; Puche-Sanz, I.; Thibault, C.; Gandaglia, G.; YAU Prostate Cancer Working Group; Tilki, Derya; Other; School of Medicine; Koç University HospitalWith the therapeutic landscape of advanced prostate cancer rapidly evolving and oncological benefits being shown for a plethora of new agents and indications, health-related quality of life (HRQOL)-associated evidence is still subpar. In the current comprehensive review, we discuss the importance of HRQOL for patients with advanced PC (metastatic hormone-sensitive prostate cancer (mHSPC), metastatic castration-resistant prostate cancer (mCRPC) and non-metastatic castrationresistant prostate cancer (nmCRPC)), and present the most frequently used tools to evaluate HRQOL in recent randomized trials. Furthermore, we discuss the ease of use of these validated questionnaires for clinicians and try to focus on the suggested appropriate use in clinical practice, as well as potential strategies for improvement of HRQOL evaluation in these clinical scenarios of advanced prostate cancer.Publication Open Access Association of B7-H3 expression with racial ancestry, immune cell density, and androgen receptor activation in prostate cancer(Wiley, 2022) Mendes, Adrianna A.; Lu, Jiayun; Kaur, Harsimar B.; Zheng, Siqun L.; Xu, Jianfeng; Hicks, Jessica; Weiner, Adam B.; Schaeffer, Edward M.; Ross, Ashley E.; Balk, Steven P.; Taplin, Mary-Ellen; Department of Chemical and Biological Engineering; Lack, Nathan Alan; Tekoğlu, Tahsin Emirhan; Faculty Member; Department of Chemical and Biological Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Sciences and Engineering; 120842; N/ABackground: B7 homolog 3 (B7-H3) is an immunomodulatory molecule that is highly expressed in prostate cancer (PCa) and belongs to the B7 superfamily, which includes PD-L1. Immunotherapies (antibodies, antibody-drug conjugates, and chimeric antigen receptor T cells) targeting B7-H3 are currently in clinical trials; therefore, elucidating the molecular and immune microenvironment correlates of B7-H3 expression may help to guide trial design and interpretation. The authors tested the interconnected hypotheses that B7-H3 expression is associated with genetic racial ancestry, immune cell composition, and androgen receptor signaling in PCa. Methods: an automated, clinical-grade immunohistochemistry assay was developed by to digitally quantify B7-H3 protein expression across 2 racially diverse cohorts of primary PCa (1 with previously reported transcriptomic data) and pretreatment and posttreatment PCa tissues from a trial of intensive neoadjuvant hormonal therapy. Results: B7-H3 protein expression was significantly lower in self-identified Black patients and was inversely correlated with the percentage African ancestry. This association with race was independent of the significant association of B7-H3 protein expression with ERG/ETS and PTEN status. B7-H3 messenger RNA expression, but not B7-H3 protein expression, was significantly correlated with regulatory (FOXP3-positive) T-cell density. Finally, androgen receptor activity scores were significantly correlated with B7-H3 messenger RNA expression, and neoadjuvant intensive hormonal therapy was associated with a significant decrease in B7-H3 protein expression. Conclusions: the current data underscore the importance of studying racially and molecularly diverse PCa cohorts in the immunotherapy era. This study is among the first to use genetic ancestry markers to add to the emerging evidence that PCa in men of African ancestry may have a distinct biology associated with B7-H3 expression. Lay Summary: B7-H3 is an immunomodulatory molecule that is highly expressed in prostate cancer and is under investigation in clinical trials. The authors determined that B7-H3 protein expression is inversely correlated with an individual's proportion of African ancestry. The results demonstrate that B7-H3 messenger RNA expression is correlated with the density of tumor T-regulatory cells. Finally, in the first paired analysis of B7-H3 protein expression before and after neoadjuvant intensive hormone therapy, the authors determined that hormone therapy is associated with a decrease in B7-H3 protein levels, suggesting that androgen signaling may positively regulate B7-H3 expression. These results may help to guide the design of future clinical trials and to develop biomarkers of response in such trials.Publication Open Access Association of XRCC3, XRCC4, BAX, and BCL-2 polymorphisms with the risk of breast cancer(Hindawi, 2022) Trabulus, Fadime Didem Can; Erhan, Duygu; Batar, Bahadır; Güven, Mehmet; Özoran, Emre; Teaching Faculty; School of Medicine; 307296Background: breast cancer is the most common malignancy in women. Genetic risk factors associated with breast cancer incidence have been identified. Aims: this study is aimed at determining the association of XRCC3 Thr241Met (rs861539), XRCC4 G(-1394) T (rs6869366) DNA repair and BAX G(-248) A (rs4645878), and BCL2 C(-938) A (rs2279115) apoptotic gene polymorphisms with breast cancer. Materials and Methods: genetic analysis was performed using peripheral blood samples. Gene polymorphisms were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. 175 patients and 158 healthy controls were enrolled in the study. Results: breast cancer risk was 5.43 times more in individuals with AA genotype of Bax G(-248) A (rs4645878) (). The risk of metastasis was 11 times with this genotype. It was associated with 6 times more risk of having a tumor larger than 2?cm. The risk of breast cancer was 2.77 times more in individuals carrying the Met/Met genotype of XRCC3 Thr241Met (rs861539) (). The risk of having advanced clinical stage (stage III+IV) with the Met/Met genotype was 4 times more increased. No relationship with breast cancer was found with XRCC4 G(-1394) T (rs6869366) and BCL2 C(-938) A (rs2279115) gene polymorphisms. Conclusion: multicenter trials using subjects with genetic variations are needed to establish the relationship between breast cancer and single gene polymorphism.Publication Open Access Atezolizumab, bevacizumab, and chemotherapy for newly diagnosed stage III or IV ovarian cancer: placebo-controlled randomized phase III trial (IMagyn050/GOG 3015/ENGOT-OV39)(Wolters Kluwer, 2021) Moore, K. N.; Bookman, M.; Sehouli, J.; Miller, A.; Anderson, C.; Scambia, G.; Myers, T.; Robison, K.; Mäenpää, J.; Willmott, L.; Colombo, N.; Thomes-Pepin, J.; Liontos, M.; Gold, M. A.; Garcia, Y.; Sharma, S. K.; Darus, C. J.; Aghajanian, C.; Okamoto, A.; Wu, X.; Safin, R.; Wu, F.; Molinero, L.; Maiya, V.; Khor, V. K.; Lin, Y. G.; Pignata, S.; Taşkıran, Çağatay; Faculty Member; School of Medicine; 134190Purpose: to evaluate the addition of the humanized monoclonal antiprogrammed death ligand-1 (PD-L1) antibody, atezolizumab, to platinum-based chemotherapy and bevacizumab in newly diagnosed stage III or IV ovarian cancer (OC). Methods: this multicenter placebo-controlled double-blind randomized phase III trial (ClinicalTrials.gov identifier: NCT03038100) enrolled patients with newly diagnosed untreated International Federation of Gynecology and Obstetrics (FIGO) stage III or IV OC who either had undergone primary cytoreductive surgery with macroscopic residual disease or were planned to receive neoadjuvant chemotherapy and interval surgery. Patients were stratified by FIGO stage, Eastern Cooperative Oncology Group performance status, tumor immune cell PD-L1 staining, and treatment strategy and randomly assigned 1:1 to receive 3-weekly cycles of atezolizumab 1,200 mg or placebo (day 1, cycles 1-22), with paclitaxel plus carboplatin (day 1, cycles 1-6) plus bevacizumab 15 mg/kg (day 1, cycles 2-22), omitting perioperative bevacizumab in neoadjuvant patients. The co-primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat and PD-L1-positive populations. Results: between March 8, 2017, and March 26, 2019, 1,301 patients were enrolled. The median progression-free survival was 19.5 versus 18.4 months with atezolizumab versus placebo, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.07; stratified log-rank P = .28), in the intention-to-treat population and 20.8 versus 18.5 months, respectively (hazard ratio, 0.80; 95% CI, 0.65 to 0.99; P = .038), in the PD-L1-positive population. The interim (immature) overall survival results showed no significant benefit from atezolizumab. The most common grade 3 or 4 adverse events were neutropenia (21% with atezolizumab v 21% with placebo), hypertension (18% v 20%, respectively), and anemia (12% v 12%). Conclusion: current evidence does not support the use of immune checkpoint inhibitors in newly diagnosed OC. Insight from this trial should inform further evaluation of immunotherapy in OC.Publication Open Access Autophagy and cancer dormancy(Frontiers, 2021) Akçay, Arzu; Akkoç, Yunus; Peker, Nesibe; Gözüaçık, Devrim; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; N/A; N/A; 40248Metastasis and relapse account for the great majority of cancer-related deaths. Most metastatic lesions are micro metastases that have the capacity to remain in a non-dividing state called "dormancy" for months or even years. Commonly used anticancer drugs generally target actively dividing cancer cells. Therefore, cancer cells that remain in a dormant state evade conventional therapies and contribute to cancer recurrence. Cellular and molecular mechanisms of cancer dormancy are not fully understood. Recent studies indicate that a major cellular stress response mechanism, autophagy, plays an important role in the adaptation, survival and reactivation of dormant cells. In this review article, we will summarize accumulating knowledge about cellular and molecular mechanisms of cancer dormancy, and discuss the role and importance of autophagy in this context.Publication Open Access Baseline hemoglobin <11.0 g/dL has stronger prognostic value than anemia status in nasopharynx cancers treated with chemoradiotherapy(Sage, 2019) Topkan, Erkan; Ekici, Nur Yücel; Özdemir, Yurday; Besen, Ali Ayberk; Yıldırım, Berna Akkuş; Mertsoylu, Hüseyin; N/A; Sezen, Duygu; Selek, Uğur; Faculty Member; Faculty Member; School of Medicine; N/A; 27211Background: to retrospectively investigate the influence of pretreatment anemia and hemoglobin levels on the survival of nasopharyngeal carcinoma patients treated with concurrent chemoradiotherapy (C-CRT). Methods: a total of 149 nasopharyngeal carcinoma patients who received C-CRT were included. All patients had received 70 Gy to the primary tumor plus the involved lymph nodes, and 59.4 Gy and 54 Gy to the intermediate- and low-risk neck regions concurrent with 1-3 cycles of cisplatin. Patients were dichotomized into non-anemic and anemic (hemoglobin <12 g/dL (women) or <13 g/dL (men)) groups according to their pre-treatment hemoglobin measures. Receiver operating characteristic (ROC) curve analysis was utilized for accessibility of a pre-treatment hemoglobin cut-off that impacts outcomes. Potential interactions between baseline anemia status and hemoglobin measures and overall survival, locoregional progression-free survival (LRPFS), and progression-free survival were assessed. Results: Anemia was evident in 36 patients (24.1%), which was related to significantly shorter overall survival (P=0.007), LRPFS (P<0.021), and progression-free survival (P=0.003) times; all three endpoints retained significance in multivariate analyses (P<0.05, for each). A baseline hemoglobin value of 11.0 g/dL exhibited significant association with outcomes in ROC curve analysis: hemoglobin <11.0 g/dL (N=26) was linked with shorter median overall survival (P<0.001), LRPFS (P=0.004), and progression-free survival (P<0.001) times, which also retained significance for all three endpoints in multivariate analyses and suggested a stronger prognostic worth for the hemoglobin Conclusion: pre-C-CRT hemoglobin <11.0 g/dL has a stronger prognostic worth than the anemia status with regard to LRPFS, progression-free survival, and overall survival for nasopharyngeal carcinoma patients.Publication Open Access beta III-Tubulin: a novel mediator of chemoresistance and metastases in pancreatic cancer(Impact Journals, 2015) McCarroll, Joshua A.; Sharbeen, George; Liu, Jie; Youkhana, Janet; Goldstein, David; McCarthy, Nigel; Limbri, Lydia F.; Dischl, Dominic; Ceyhan, Gueralp O.; Johns, Amber L.; Biankin, Andrew V.; Kavallaris, Maria; Phillips, Phoebe A.; N/A; Erkan, Murat Mert; Faculty Member; School of Medicine; 214689Pancreatic cancer is a leading cause of cancer-related deaths in Western societies. This poor prognosis is due to chemotherapeutic drug resistance and metastatic spread. Evidence suggests that microtubule proteins namely, beta-tubulins are dysregulated in tumor cells and are involved in regulating chemosensitivity. However, the role of beta-tubulins in pancreatic cancer are unknown. We measured the expression of different beta-tubulin isotypes in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Next, we used RNAi to silence beta III-tubulin expression in pancreatic cancer cells, and measured cell growth in the absence and presence of chemotherapeutic drugs. Finally, we assessed the role of beta III-tubulin in regulating tumor growth and metastases using an orthotopic pancreatic cancer mouse model. We found that beta III-tubulin is highly expressed in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Further, we demonstrated that silencing beta III-tubulin expression reduced pancreatic cancer cell growth and tumorigenic potential in the absence and presence of chemotherapeutic drugs. Finally, we demonstrated that suppression of beta III-tubulin reduced tumor growth and metastases in vivo. Our novel data demonstrate that beta III-tubulin is a key player in promoting pancreatic cancer growth and survival, and silencing its expression may be a potential therapeutic strategy to increase the long-term survival of pancreatic cancer patients.