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notch cancer

Jeong Hwan Park, Cheol Lee, Mee Soo Chang, Kwangsoo Kim, Seongmin Choi, Hyunjung Lee, Hyun-Seob Lee, Kyung Chul Moon
Tuberous sclerosis complex-associated renal cell carcinoma (TSC-RCC) has distinct clinical and histopathologic features and is considered a specific subtype of RCC. The genetic alterations of TSC1 or TSC2 are responsible for the development of TSC. In this study, we assessed the mTOR pathway activation and aimed to evaluate molecular characteristics and pathogenic pathways of TSC-RCC. Two cases of TSC-RCC, one from a 31-year-old female and the other from an 8-year-old male, were assessed. The mTOR pathway activation was determined by immunohistochemistry...
June 17, 2018: Translational Oncology
Guoju Hong, Vincent Kuek, Jiaxi Shi, Lin Zhou, Xiaorui Han, Wei He, Jennifer Tickner, Heng Qiu, Qiushi Wei, Jiake Xu
Epidermal growth factor-like domain-containing protein 7 (EGFL7), a member of the epidermal growth factor (EGF)-like protein family, is a potent angiogenic factor expressed in many different cell types. EGFL7 plays a vital role in controlling vascular angiogenesis during embryogenesis, organogenesis, and maintaining skeletal homeostasis. It regulates cellular functions by mediating the main signaling pathways (Notch, integrin) and EGF receptor cascades. Accumulating evidence suggests that Egfl7 plays a crucial role in cancer biology by modulating tumor angiogenesis, metastasis, and invasion...
June 19, 2018: Journal of Cellular Physiology
Zixin Huang, Shuibin Lin, Chongde Long, Xin Zhou, Yuting Fan, Xielan Kuang, Jia He, Jie Ning, Han Zhang, Qingjiong Zhang, Huangxuan Shen
Background: Doxorubicin is a widely used chemotherapy drug for the treatment of a variety of cancers, however it also has serious side effects such as anaphylaxis and heart damage. Therefore, it's very important to understand the downstream molecular pathways that are essential for Doxorubicin function in cancer treatment. Methods: HeLa S3 cells were treated with different concentrations of Doxorubicin for 24 hours. Then, the mRNA levels of Notch pathway components in the Doxorubicin treated cells were determined by Real-Time qRT-PCR...
2018: Cancer Management and Research
Richa Tripathi, Gayatri Rath, Showket Hussain, Poonam Jawanjal, Kapil Bandil, Vishwas Sharma, Mausumi Bharadwaj, Ravi Mehrotra
The majority of cervical cancer (CC) cases are attributable to HPV infection. Altered Notch pathway signals and HPV are believed to modify clinicopathogenesis of CC, however, the involvement of each molecular player and its mechanism is still not known. Jagged-1 (JAG1) is one of the ligands that induce Notch pathway. The involvement of JAG1 in the modulation of a disease condition is not very clear. Hence, this study aims to study the role of JAG1 in HPV-16/18 associated different histological sub-types of CC, especially ADC...
June 19, 2018: Scientific Reports
L-Q Li, D Pan, S-W Zhang, D -Y-Xie, X-L Zheng, H Chen
OBJECTIVE: Gastric cancer is the most common gastrointestinal malignancy and the leading cause of cancer-related deaths in East Asia. Increasing evidence has revealed that autophagy is closely associated with tumor initiation and progression. The present work aimed to investigate the role of autophagy in adjuvant chemotherapy for gastric cancer. MATERIALS AND METHODS: Gastric cancer stem cells (CSCs) were isolated from gastric cancer cell lines using the cell surface markers CD44 and CD54 and cultured in a three-dimensional cell culture system...
June 2018: European Review for Medical and Pharmacological Sciences
Fokhrul Hossain, Samarpan Majumder, Deniz A Ucar, Paulo C Rodriguez, Todd E Golde, Lisa M Minter, Barbara A Osborne, Lucio Miele
Cancer immunotherapy, which stimulates or augments host immune responses to treat malignancies, is the latest development in the rapidly advancing field of cancer immunology. The basic principles of immunotherapies are either to enhance the functions of specific components of the immune system or to neutralize immune-suppressive signals produced by cancer cells or tumor microenvironment cells. When successful, these approaches translate into long-term survival for patients. However, durable responses are only seen in a subset of patients and so far, only in some cancer types...
2018: Frontiers in Immunology
Manish D Mair, Noopur Sawarkar, Santosh Nikam, Rajiv Sarin, Deepa Nair, Tejpal Gupta, Pankaj Chaturvedi, Anil D'cruz, Sudhir Nair
INTRODUCTION: In the absence of any robust data supporting the TNM classification of T4 buccal mucosa cancers, we did this prospective study to compare the oncologic outcomes of T4a and T4b buccal mucosa cancer patients. PATIENTS AND METHODS: This is a prospective study of 210 treatment naïve T4 buccal mucosa cancer patients. All patients underwent upfront radical surgery followed by adjuvant radiotherapy (RT)/chemoradiotherapy (CCRT). This is the largest prospective series in the literature on T4 buccal cancers...
July 2018: Oral Oncology
Jian-Heng Peng, Xiao-Lin Wang, Liang Ran, Jun-Long Song, Zhi-Ting Zhang, Xin Liu, Hong-Yuan Li
This study aimed to investigate the effect of inhibiting the Notch signaling pathway on the radiosensitivity of breast cancer cells. Human breast cancer cell lines (MCF-7 and T47D) were selected and treated with radiation of different doses. Cells were treated with Gamma secretase inhibitor (GSI) to analyze the effects of GSI on the Notch signaling, which were detected by Immunofluorescence assay, RT-qPCR, and Western blot analysis. Besides, Transwell assay, Scratch test, colony formation assay, MTT assay, and flow cytometry were conducted to show the effects of GSI on the invasion and migration, survival fraction, cell viability, and apoptosis of MCF-7 and T47D cells after radiation therapy...
June 15, 2018: Journal of Cellular Biochemistry
Stewart G Martin, Marie N Lebot, Bhudsaban Sukkarn, Graham Ball, Andrew R Green, Emad A Rakha, Ian O Ellis, Sarah J Storr
G protein-coupled oestrogen receptor 1 (GPER), also called G protein-coupled receptor 30 (GPR30), is attracting considerable attention for its potential role in breast cancer development and progression. Activation by oestrogen (17β-oestradiol; E2) initiates short term, non-genomic, signalling events both in vitro and in vivo . Published literature on the prognostic value of GPER protein expression in breast cancer indicates that further assessment is warranted. We show, using immunohistochemistry on a large cohort of primary invasive breast cancer patients (n=1245), that low protein expression of GPER is not only significantly associated with clinicopathological and molecular features of aggressive behaviour but also significantly associated with adverse survival of breast cancer patients...
May 25, 2018: Oncotarget
Arnab Chattopadhyay, Xinying Yang, Pallavi Mukherjee, Dawoud Sulaiman, Hannah R Fogelman, Victor Grijalva, Steven Dubinett, Tonya C Wasler, Manash K Paul, Ramin Salehi-Rad, Julia J Mack, M Luisa Iruela-Arispe, Mohamad Navab, Alan M Fogelman, Srinivasa T Reddy
Having demonstrated that apolipoprotein A-I (apoA-I) mimetic peptides ameliorate cancer in mouse models, we sought to determine the mechanism for the anti-tumorigenic function of these peptides. CT-26 cells (colon cancer cells that implant and grow into tumors in the lungs) were injected into wild-type BALB/c mice. The day after injection, mice were either continued on chow or switched to chow containing 0.06% of a concentrate of transgenic tomatoes expressing the apoA-I mimetic peptide 6F (Tg6F). After four weeks, the number of lung tumors was significantly lower in Tg6F-fed mice...
June 13, 2018: Scientific Reports
Lu Wang, Guo Dai, Jian Yang, Wanrong Wu, Wei Zhang
BACKGROUND The Notch signaling pathway has been reported to play a pivotal role in tumorigenesis. Emerging evidence has demonstrated that the Notch signaling pathway regulates several cellular processes. The present study investigated the effect of the Notch signaling pathway on cell growth, invasiveness, and drug resistance, as well as epithelial-mesenchymal transition (EMT), of cervical cancer cells. MATERIAL AND METHODS We used quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis to measure the expression level of Notch2...
June 14, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Hai-Yan Song, Ying Wang, Hong Lan, Yu-Xiang Zhang
Pancreatic cancer is the fourth leading cause of cancer-associated mortality in developed countries. Pancreatic ductal adenocarcinoma (PDAC) accounts for ~90% of all pancreatic cancer cases. The Notch signaling pathway serves a crucial role in embryonic development, as well as during the tumorigenesis of different types of cancer. However, Notch signaling serves either oncogenic or tumor suppressor roles depending on the tissue type. There are four Notch receptors (Notch1-4) and five ligands [Jagged1, Jagged2, δ-like ligand protein (DLL)1, DLL3 and DLL4]; therefore, it has been suggested that the different Notch receptors serve distinct roles in the same type of tissue...
July 2018: Experimental and Therapeutic Medicine
Deep Shah, Debra Wyatt, Andrew Baker, Patricia Simms, Daniel S Peiffer, Michelle L Fernandez, Emad A Rakha, Andrew R Green, Aleksandra Filipovic, Lucio Miele, Clodia Osipo
PURPOSE: Human Epidermal Growth Factor Receptor 2 (HER2) positive breast cancer is driven by cells possessing stem-like properties of self-renewal and differentiation, referred to as Cancer Stem Cells (CSCs). CSCs are implicated in radiotherapy, chemotherapy resistance, and tumor recurrence. Notch promotes breast CSCs survival and self-renewal, and overexpression of Notch1 and the Notch ligand Jagged1 predict poor outcome. Resistance to anti-HER2 therapy in HER2+ breast cancer requires Notch1, and that combination of trastuzumab and a Gamma Secretase Inhibitor (GSI) prevents tumor relapse in xenograft models...
June 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Qiang-Hua Zhou, Chuang-Zhong Deng, Zai-Shang Li, Jie-Ping Chen, Kai Yao, Kang-Bo Huang, Ting-Yu Liu, Zhuo-Wei Liu, Zi-Ke Qin, Fang-Jian Zhou, Wenlin Huang, Hui Han, Ran-Yi Liu
Cell line models are essential tools to study the molecular mechanisms underlying tumor initiation and progression. There are limited treatment options for penile squamous cell carcinoma (PSCC), accounting for 1-2% of male tumors in developing countries, and limited progress in preclinical research in PSCC due to lacking available models with identified genomic characteristics. Here, biological and molecular characteristics and whole-genomic alterations were analyzed in a panel of PSCC cell lines newly established in our laboratory...
June 7, 2018: Cell Death & Disease
Monika A Jarzabek, William R Proctor, Jennifer Vogt, Rupal Desai, Patrick Dicker, Gary Cain, Rajiv Raja, Jens Brodbeck, Dale Stevens, Eric P van der Stok, John W M Martens, Cornelis Verhoef, Priti S Hegde, Annette T Byrne, Jacqueline M Tarrant
Drug-related sinusoidal dilatation (SD) is a common form of hepatotoxicity associated with oxaliplatin-based chemotherapy used prior to resection of colorectal liver metastases (CRLM). Recently, hepatic SD has also been associated with anti-delta like 4 (DLL4) cancer therapies targeting the NOTCH pathway. To investigate the hypothesis that NOTCH signaling plays an important role in drug-induced SD, gene expression changes were examined in livers from anti-DLL4 and oxaliplatin-induced SD in non-human primate (NHP) and patients, respectively...
2018: PloS One
Marta Portela, Liu Yang, Sayantanee Paul, Xia Li, Alexey Veraksa, Linda M Parsons, Helena E Richardson
Epithelial cell polarity is linked to the control of tissue growth and tumorigenesis. The tumor suppressor and cell polarity protein lethal-2-giant larvae (Lgl) promotes Hippo signaling and inhibits Notch signaling to restrict tissue growth in Drosophila melanogaster Notch signaling is greater in lgl mutant tissue than in wild-type tissue because of increased acidification of endosomal vesicles, which promotes the proteolytic processing and activation of Notch by γ-secretase. We showed that the increased Notch signaling and tissue growth defects of lgl mutant tissue depended on endosomal vesicle acidification mediated by the vacuolar adenosine triphosphatase (V-ATPase)...
June 5, 2018: Science Signaling
Kamini Kaushal, Ainsley Mike Antao, Kye-Seong Kim, Suresh Ramakrishna
The ability of cancers to evade conventional treatments, such as chemotherapy and radiation therapy, has been attributed to a subpopulation of cancer stem cells (CSCs). CSCs are regulated by mechanisms similar to those that regulate normal stem cells (NSCs), including processes involving ubiquitination and deubiquitination enzymes (DUBs) that regulate the expression of various factors, such as Notch, Wnt, Sonic Hedgehog (Shh), and Hippo. In this review, we discuss the roles of various DUBs involved in the regulation of core stem cell transcription factors and CSC-related proteins that are implicated in the modulation of cellular processes and carcinogenesis...
June 1, 2018: Drug Discovery Today
Nikolaos Tsoukalas, Eleni Aravantinou-Fatorou, Panagiotis Baxevanos, Maria Tolia, Konstantinos Tsapakidis, Michail Galanopoulos, Michail Liontos, George Kyrgias
Small cell lung cancer (SCLC) remains one of the most lethal malignancies and a major health riddle. The therapeutic options are limited. The combination of etoposide or irinotecan with platinum chemotherapy is the standard of care at any stage. The last decade systemic efforts have been done to reveal specific therapeutic targets for small cell lung carcinomas. In this review, we focus on the new therapeutic strategies of SCLC, including immune-related treatment that may change the prognosis of the disease...
April 2018: Annals of Translational Medicine
Mian Xie, Shenhai Wei, Xiaojun Wu, Xiaoxiang Li, You You, Chaosheng He
INTRODUCTION: Adenoid cystic carcinoma (ACC) of the trachea lacks of well-characterized molecular markers. There is currently no specific treatment for metastatic ACC of the trachea. This study aimed to identify genomic mutations of Notch pathway and investigate the efficacy of NOTCH inhibitor in ACC of the trachea. METHODS: 73 Patients with ACC of the trachea at four institutions from 2008 to 2016 were identified. Analysis of hotspot mutations in cancer-related genes of Notch pathway was performed using next generation sequencing...
July 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Maria Di Bari, Valeria Bevilacqua, Antonella De Jaco, Pietro Laneve, Roberta Piovesana, Laura Trobiani, Claudio Talora, Elisa Caffarelli, Ada Maria Tata
Glioblastoma (GBM) is the most aggressive human brain tumor. The high growth potential and decreased susceptibility to apoptosis of the glioma cells is mainly dependent on genetic amplifications or mutations of oncogenic or pro-apoptotic genes, respectively. We have previously shown that the activation of the M2 acetylcholine muscarinic receptors inhibited cell proliferation and induced apoptosis in two GBM cell lines and cancer stem cells. The aim of this study was to delve into the molecular mechanisms underlying the M2-mediated cell proliferation arrest...
May 31, 2018: International Journal of Molecular Sciences
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