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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/3
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Publication Metadata only Genome-wide RNA and DNA high throughput sequencing reveals proinflammatory and death gene signatures in head and neck squamous cell carcinoma lines with different HPV status(American Association for Cancer Research (AACR), 2014) Yang, Xinping; Cheng, Hui; Si, Han; Saleh, Anthony; Coupar, Jamie; Ferris, Robert L.; Yarbrough, Wendell G.; Prince, Mark E.; Carey, Thomas E.; Van Waes, Carter; Chen, Zhong; N/A; N/A; Department of Computer Engineering; N/A; Department of Computer Engineering; Maiorov, Emine Güven; Keskin, Özlem; Gürsoy, Attila; PhD Student; Faculty Member; Faculty Member; N/A; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; N/A; 26605; 8745; N/AN/APublication Metadata only Head and neck cancers promote an inflammatory transcriptome through coactivation of classic and alternative NF-κB pathways(Amer Assoc Cancer Research, 2019) Yang, Xinping; Cheng, Hui; Chen, Jianhong; Wang, Ru; Saleh, Anthony; Si, Han; Lee, Steven; Nussinov, Ruth; Fang, Jugao; Van Waes, Carter; Chen, Zhong; N/A; Department of Chemical and Biological Engineering; Department of Computer Engineering; Department of Chemical and Biological Engineering; Department of Computer Engineering; Maiorov, Emine Güven; Keskin, Özlem; Gürsoy, Attila; PhD Student; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; 26605; 8745Head and neck squamous cell carcinomas (HNSCC) promote inflammation in the tumor microenvironment through aberrant NF-kappa B activation, but the genomic alterations and pathway networks that modulate NF-kappa B signaling have not been fully dissected. Here, we analyzed genome and transcriptome alterations of 279 HNSCC specimens from The Cancer Genome Atlas (TCGA) cohort and identified 61 genes involved in NF-kappa B and inflammatory pathways. The top 30 altered genes were distributed across 96% of HNSCC samples, and their expression was often correlated with genomic copy-number alterations (CNA). Ten of the amplified genes were associated with human papilloma virus (HPV) status. We sequenced 15 HPV- and 11 HPV+ human HNSCC cell lines, and three oral mucosa keratinocyte lines, and supervised clustering revealed that 28 of 61 genes exhibit altered expression patterns concordant with HNSCC tissues and distinct signatures related to their HPV status. RNAi screening using an NF-kappa B reporter line identified 16 genes that are induced by TNF alpha or Lymphotoxin-beta (LT beta) and implicated in the classic and/or alternative NF-kappa B pathways. Knockdown of TNFR, LTBR, or selected downstream signaling components established cross-talk between the classic and alternative NF-kappa B pathways. TNF alpha and LT beta induced differential gene expression involving the NF-kappa B, IFN gamma, and STAT pathways, inflammatory cytokines, and metastasis-related genes. Improved survival was observed in HNSCC patients with elevated gene expression in T-cell activation, immune checkpoints, and IFN gamma and STAT pathways. These gene signatures of NF-kappa B activation, which modulate inflammation and responses to the immune therapy, could serve as potential biomarkers in future clinical trials.Publication Metadata only The key role of calmodulin in kras-driven adenocarcinomas(Amer Assoc Cancer Research, 2015) Nussinov, Ruth; Tsai, Chung-Jung; Jang, Hyunbum; N/A; Department of Chemical and Biological Engineering; Department of Computer Engineering; Department of Chemical and Biological Engineering; Department of Computer Engineering; Muratçıoğlu, Serena; Keskin, Özlem; Gürsoy, Attila; PhD Student; Faculty Member; Faculty Member; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; 26605; 8745KRAS4B is a highly oncogenic splice variant of the KRAS isoform. It is the only isoform associated with initiation of adenocarcinomas. Insight into why and how KRAS4B can mediate ductal adenocarcinomas, particularly of the pancreas, is vastly important for its therapeutics. Here we point out the overlooked critical role of calmodulin (CaM). Calmodulin selectively binds to GTP-bound K-Ras4B; but not to other Ras isoforms. Cell proliferation and growth require the MAPK (Raf/MEK/ERK) and PI3K/Akt pathways. We propose that Ca2+/calmodulin promote PI3K alpha/Akt signaling, and suggest how. The elevated calcium levels clinically observed in adenocarcinomas may explain calmodulin's involvement in recruiting and stimulating PI3K alpha through interaction with its n/cSH2 domains as well as K-Ras4B; importantly, it also explains why K-Ras4B specifically is a key player in ductal carcinomas, such as pancreatic (PDAC), colorectal (CRC), and lung cancers. We hypothesize that calmodulin recruits and helps activate PI3K alpha at the membrane, and that this is the likely reason for Ca2+/calmodulin dependence in adenocarcinomas. Calmodulin can contribute to initiation/progression of ductal cancers via both PI3K alpha/Akt and Raf/MEK/ERK pathways. Blocking the K-Ras4B/MAPK pathway and calmodulin/PI3Ka binding in a K-Ras4B/calmodulin/PI3K alpha trimer could be a promising adenocarcinoma-specific therapeutic strategy.Publication Metadata only Experiences of breast cancer survivors during the COVID-19 pandemic: a qualitative study(Oncology Nursing Soc, 2021) N/A; N/A; N/A; Department of Computer Engineering; N/A; Department of Computer Engineering; Seven, Memnun; Bağçivan, Gülcan; Paşalak, Şeyma İnciser; Özkasap, Öznur; Selçukbiricik, Fatih; Faculty Member; Faculty Member; PhD Student; Faculty Member; Faculty Member; School of Nursing; School of Nursing; Graduate School of Health Sciences; College of Engineering; School of Medicine; 32470; 261422; 125009; 113507; 202015Purpose: This study aimed to explore the impacts of the COVID-19 pandemic on the quality of life of breast cancer survivors. Methods: This qualitative descriptive study included 18 breast cancer survivors who completed cancer treatment within the last five years in Istanbul, Turkey. A directed content analysis was performed using the quality-of-life domains as guiding themes. Results: The mean age was 51 ± 5.9, and the average months since active treatment were 26.5 ± 9.8 (9-48). Six themes and associated categories are as follows: Physical functioning; Changes in physical activity and weight, new physical symptoms, Role functioning; Work-life, changes in household chores, Emotional functioning; Emotional changes, fear of having the COVID-19 infection, Cognitive Functioning; Risk Perception about the COVID-19 infection, reactions to the COVID-19 pandemic' measures, Social Functioning; Familial relationship changes, social interactions, General Health/Utilization of Healthcare services; Changes in routine follow-ups, changes in diet. Conclusion: Breast cancer survivors had different challenges causing new physical and psychological symptoms such as lymphedema, pain, burnout, and anxiety that may have long-term effects on their quality of life.Publication Metadata only Androgen receptor binding sites are highly mutated in prostate cancer(American Association for Cancer Research (AACR), 2018) N/A; Department of Industrial Engineering; Department of Computer Engineering; Department of Chemical and Biological Engineering; N/A; Department of Industrial Engineering; Department of Computer Engineering; Department of Chemical and Biological Engineering; Morova, Tunç; Gönen, Mehmet; Gürsoy, Attila; Keskin, Özlem; Lack, Nathan Alan; N/A; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; College of Engineering; College of Engineering; College of Engineering; School of Medicine; N/A; 237468; 8745; 26605; 120842Publication Metadata only The structural network of inflammation and cancer: merits and challenges(Academic Press Ltd- Elsevier Science Ltd, 2013) Nussinov, Ruth; N/A; Department of Chemical and Biological Engineering; Department of Computer Engineering; Department of Chemical and Biological Engineering; Department of Computer Engineering; Maiorov, Emine Güven; Keskin, Özlem; Gürsoy, Attila; PhD Student; Faculty Member; Faculty Member; The Center for Computational Biology and Bioinformatics (CCBB); Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; 26605; 8745Inflammation, the first line of defense against pathogens can contribute to all phases of tumorigenesis, including tumor initiation, promotion and metastasis. Within this framework, the Toll-like receptor (TLR) pathway plays a central role in inflammation and cancer. Although extremely useful, the classical representation of this, and other pathways in the cellular network in terms of nodes (proteins) and edges (interactions) is incomplete. Structural pathways can help complete missing parts of such diagrams: they demonstrate in detail how signals coming from different upstream pathways merge and propagate downstream, how parallel pathways compensate each other in drug resistant mutants, how multi-subunit signaling complexes form and in particular why they are needed and how they work, how allosteric events can control these proteins and their pathways, and intricate details of feedback loops and how kick in. They can also explain the mechanisms of some oncogenic SNP mutations. Constructing structural pathways is a challenging task. Here, our goal is to provide an overview of inflammation and cancer from the structural standpoint, focusing on the TLR pathway. We use the powerful PRISM (PRotein Interactions by Structural Matching) tool to reveal important structural information of interactions in and within key orchestrators of the TLR pathway, such as MyD88.Publication Metadata only Exploratory analyses of symptom cluster change during chemotherapy in women with breast cancer receiving chemotherapy(Oncology Nursing Soc, 2022) N/A; N/A; N/A; Department of Computer Engineering; N/A; Department of Computer Engineering; Seven, Memnun; Bağçivan, Gülcan; Paşalak, Şeyma İnciser; Özkasap, Öznur; Selçukbiricik, Fatih; Faculty Member; Faculty Member; PhD Student; Faculty Member; Faculty Member; School of Nursing; School of Nursing; Graduate School of Health Sciences; College of Engineering; School of Medicine; 32470; 261422; 125009; 113507; 202015N/APublication Metadata only The effect of the use of a mobile symptom management app during the chemotherapy of breast cancer(Elsevier, 2021) Seven, M.; Department of Computer Engineering; N/A; N/A; N/A; Department of Computer Engineering; Özkasap, Öznur; Selçukbiricik, Fatih; Paşalak, Şeyma İnciser; Bağçivan, Gülcan; Faculty Member; Faculty Member; PhD Student; Faculty Member; College of Engineering; School of Medicine, Graduate School of Health Sciences; School of Nursing; 113507; 202015; 125009; 261422N/APublication Metadata only Altered inflammatory and death pathways in head and neck cell lines model genomic and expression signatures identified in the cancer genome Atlas(American Association for Cancer Research, 2015) Yang, Xinping; Cheng, Hui; Saleh, Anthony; Cornelius, Shaleeka; Nussinov, Ruth; Van Weas, Carter; Chen, Zhong; Department of Computer Engineering; Department of Chemical and Biological Engineering; Department of Computer Engineering; Department of Chemical and Biological Engineering; Maiorov, Emine Güven; Keskin, Özlem; Gürsoy, Attila; PhD Student; Faculty Member; Faculty Member; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; 26605; 8745