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Cancer stem cell

Yuhan Zhao, Lihua Wu, Xuetian Yue, Cen Zhang, Jianming Wang, Jun Li, Xiaohui Sun, Yiming Zhu, Zhaohui Feng, Wenwei Hu
Tumor suppressor p53 prevents early death due to cancer development. However, the role of p53 in aging process and longevity has not been well-established. In humans, single nucleotide polymorphism (SNP) with either arginine (R72) or proline (P72) at codon 72 influences p53 activity; the P72 allele has a weaker p53 activity and function in tumor suppression. Here, employing a mouse model with knock-in of human TP53 gene carrying codon 72 SNP, we found that despite increased cancer risk, P72 mice that escape tumor development display a longer lifespan than R72 mice...
March 20, 2018: ELife
D P N Gonçalves, D M Park, T L Schmidt, C Werner
Glioblastoma multiforme (GBM) contains a population of tumor initiating stem-like cells, termed cancer stem cells (CSCs). These CSCs, which are resistant to chemo- and radiotherapy, are thought to persist after treatment and drive tumor recurrence. Thus, it is believed that the elimination of CSCs can lead to GBM remission. GBM CSCs express Nestin on their surface, and can be therefore targeted via this protein. Gold nanorods (AuNRs) functionalized with an engineered, modular peptide that recognizes Nestin (NesPEG-AuNRs) were used to target the models of solid tumors originated from human GBM CSC multicellular tumor spheroids (MCTS)...
March 20, 2018: Biomaterials Science
Stefan Bröer
Amino acids perform a variety of functions in cells and organisms, particularly in the synthesis of proteins, as energy metabolites, neurotransmitters, and precursors for many other molecules. Amino acid transport plays a key role in all these functions. Inhibition of amino acid transport is pursued as a therapeutic strategy in several areas, such as diabetes and related metabolic disorders, neurological disorders, cancer, and stem cell biology. The role of amino acid transporters in these disorders and processes is well established, but the implementation of amino acid transporters as drug targets is still in its infancy...
April 2018: SLAS Discovery
Dhanya Lakshmi Narayanan, Shubha R Phadke
Stem cell transplantation and cord blood banking have received much popularity among general public and medical professionals in the recent past. But information about the scientific aspects, its utility and limitations is incomplete amongst laypersons as well as many medical practitioners. Stem cells differ from all other types of cells in the human body because of their ability to multiply in order to self perpetuate and differentiate into specialized cells. Stems cells could be totipotent, multipotent, pluripotent, oligopotent or unipotent depending on the type of cells that can arise or differentiate from them...
March 20, 2018: Indian Journal of Pediatrics
Gurpreet Kaur, Praveen Sharma, Nilambra Dogra, Sandeep Singh
The cells of malignant cancers result in the evolution of cells with stem-like characteristics, commonly known as cancer stem cells (CSCs). Progress of anticancer therapies is severely hampered because of disease relapse mostly in a more aggressive form due to CSCs. These CSCs are more or less like embryonic or tissue stem cells, known for their capacity of self-renewal, exactly recapitulate of the original tumor. Deregulation of key stem cell pathways like Wnt, Hedgehog (Hh), and Notch is attributed towards the rise of CSCs...
March 20, 2018: Current Treatment Options in Oncology
Md Saiful Islam Roney, Song-Kyu Park
Cancer is one of the deadliest diseases in the world. Despite extensive studies, treating metastatic cancers remains challenging. Years of research have linked a rare set of cells known as cancer stem cells (CSCs) to drug resistance, leading to the suggestion that eradication of CSCs might be an effective therapeutic strategy. However, few drug candidates are active against CSCs. New drug discovery is often a lengthy process. Drug screening has been advantageous in identifying drug candidates. Current understanding of cancer biology has revealed various clues to target cancer from different points of view...
March 19, 2018: Archives of Pharmacal Research
Catherine A Lozupone
In recent years, there has been a deluge of papers linking altered microbiome compositions to a myriad of diseases. Mechanistic insight into microbial drivers of disease phenotypes is essential for translation to novel therapies. A key mechanism by which microbes influence health is immune modulation by components of their capsule and cell envelope and their metabolites. A major research focus of my laboratory is to gain mechanistic insight into which microbes modulate host immunity generally and in the context of disease...
March 2018: MSystems
Qi-Bing Wu, Xin Sheng, Ning Zhang, Ming-Wei Yang, Fan Wang
Colorectal cancer (CRC) is among the main tumor-related causes of death worldwide. The fact that the majority of the patients develop resistance to chemoradiotherapy (CRT) is a major obstacle for the treatment of CRC. In order to develop more effective treatment strategies, it is crucial to elucidate the mechanisms underlying the development of resistance to CRT. Several studies have recently indicated the regulatory effects of microRNAs (miRNAs) in response to antitumor agents. For example, miR-34a attenuates the chemoresistance of colon cancer to 5-FU by inhibiting E2F3 and SIRT1...
April 2018: Molecular and Clinical Oncology
Jiao Ji, Yan Yu, Zhi-Ling Li, Ming-Yuan Chen, Rong Deng, Xiang Huang, Guang-Feng Wang, Meng-Xia Zhang, Qi Yang, Senthilkumar Ravichandran, Gong-Kan Feng, Xue-Lian Xu, Chen-Lu Yang, Miao-Zhen Qiu, Lin Jiao, Dajun Yang, Xiao-Feng Zhu
Rationale: Nasopharyngeal carcinoma (NPC) is the most frequent head and neck tumor in South China. The presence of cancer stem cells (CSCs) in NPC contributes to tumor maintenance and therapeutic resistance, while the ability of CSCs to escape from the apoptosis pathway may render them the resistant property to the therapies. Inhibitor of apoptosis proteins family proteins (IAPs), which are overexpressed in nasopharyngeal carcinoma stem cells, may play an important role in maintaining nasopharyngeal cancer stem cell properties...
2018: Theranostics
Mitsuaki Nishioka, Yutaka Suehiro, Kouhei Sakai, Toshihiko Matsumoto, Naoko Okayama, Hidekazu Mizuno, Koji Ueno, Nobuaki Suzuki, Shinichi Hashimoto, Taro Takami, Shoichi Hazama, Hiroaki Nagano, Isao Sakaida, Takahiro Yamasaki
Tumor necrosis factor receptor superfamily member 19 ( TROY ) is involved in the Wnt/β-catenin signaling pathway and interacts with leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5), which is a well-known biomarker of cancer stem cells and a prognostic marker of colorectal cancer (CRC). Because there have been no studies to evaluate the prognostic significance of TROY , we performed the present study to determine whether TROY can be a prognostic biomarker in CRC patients. We evaluated TROY expression levels in 100 CRC tissues by quantitative real-time PCR and investigated the association of TROY expression levels with clinicopathologic features...
April 2018: Oncology Letters
Shingo Kishi, Rina Fujiwara-Tani, Yi Luo, Isao Kawahara, Kei Goto, Kiyomu Fujii, Hitoshi Ohmori, Chie Nakashima, Takamitsu Sasaki, Hiroki Kuniyasu
Trans fatty acids (TFAs) are risk factors for cardiovascular disorders, and the cancer-promoting effects of TFAs have been previously reported. The present study examined the effects and signaling of elaidic acid (EA), a TFA, in colorectal cancer (CRC) cells. Oral intake of EA was found to increase metastasis of HT29 human CRC cells. Results indicated that, in the plasma membrane, EA was integrated into cholesterol rafts, which contain epidermal growth factor receptors (EGFR). EA increased nanog and c-myc, and decreased PGC-1A through lipid raft-associated EGFR signaling in HT29 cells...
April 2018: Oncology Letters
Yuhua Chen, Lingling Meng, Haitao Shang, Qian Dou, Zhiwen Lu, Liping Liu, Zhijun Wang, Xingxing He, Yuhu Song
βII-Spectrin (β2SP), a Smad3/4 adaptor protein during transforming growth factor (TGF) β/Smad signal pathway, plays a critical role in suppressing hepatocarcinogenesis. Dedifferentiation is a distinctive feature of cancer progression. Therefore, we investigated whether the disruption of β2SP contributed to tumorigenesis of hepatocellular carcinoma (HCC) through the dedifferentiation. Down-regulation of β2SP in hepatocytes was observed in cirrhotic liver and HCC. The level of β2SP expression was closely associated with the differentiation status of hepatocytes in rat model of hepatocarcinogenesis and clinical specimens...
March 19, 2018: Cell Death & Disease
Tao Wang, Zhong-Yi Qin, Liang-Zhi Wen, Yan Guo, Qin Liu, Zeng-Jie Lei, Wei Pan, Kai-Jun Liu, Xing-Wei Wang, Shu-Jie Lai, Wen-Jing Sun, Yan-Ling Wei, Lei Liu, Ling Guo, Yu-Qin Chen, Jun Wang, Hua-Liang Xiao, Xiu-Wu Bian, Dong-Feng Chen, Bin Wang
The evolutionarily conserved Hippo signaling pathway is a key regulator of stem cell self-renewal, differentiation, and organ size. While alterations in Hippo signaling are causally linked to uncontrolled cell growth and a broad range of malignancies, genetic mutations in the Hippo pathway are uncommon and it is unclear how the tumor suppressor function of the Hippo pathway is disrupted in human cancers. Here, we report a novel epigenetic mechanism of Hippo inactivation in the context of hepatocellular carcinoma (HCC)...
March 19, 2018: Cell Death and Differentiation
Lin Jia, Dinglan Wu, Yuliang Wang, Wenxing You, Zhu Wang, Lijia Xiao, Ganhui Cai, Zhenyu Xu, Chang Zou, Fei Wang, Jeremy Yuen-Chun Teoh, Chi-Fai Ng, Shan Yu, Franky L Chan
The metastatic castration-resistant prostate cancer (CRPC) is a lethal form of prostate cancer, in which the expression of androgen receptor (AR) is highly heterogeneous. Indeed, lower AR expression and attenuated AR signature activity is shown in CRPC tissues, especially in the subset of neuroendocrine prostate cancer (NEPC) and prostate cancer stem-like cells (PCSCs). However, the significance of AR downregulation in androgen insensitivity and de-differentiation of tumor cells in CRPC is poorly understood and much neglected...
March 20, 2018: Oncogene
Min Liu, Yen-Lin Chen, Yao-Haur Kuo, Mei-Kuang Lu, Chia-Ching Liao
Sapindus mukorossi is a deciduous plant and has recently been recognized to have anticancer property. In the present study, we discovered that S. mukorossi leaf and stem aqueous extract (SaM) contained two polysaccharides mainly made of myo-inositol, galactose, glucose, and fructose and the aim of this study was to investigate the antitumor property the aqueous extract SaM. In vitro treatment of SaM diminished proliferative potential of lung adenocarcinomic cells and induced intracellular oxidative stress, as well as necrotic cell death...
March 19, 2018: Scientific Reports
Amy Reilein, David Melamed, Simon Tavaré, Daniel Kalderon
Cancer-initiating gatekeeper mutations that arise in stem cells would be especially potent if they stabilize and expand an affected stem cell lineage. It is therefore important to understand how different stem cell organization strategies promote or prevent variant stem cell amplification in response to different types of mutation, including those that activate proliferation. Stem cell numbers can be maintained constant while producing differentiated products through individually asymmetrical division outcomes or by population asymmetry strategies in which individual stem cell lineages necessarily compete for niche space...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Stephen Keysar, Justin Eagles, Bettina Miller, Brian C Jackson, Farshad N Chowdhury, Julie Reisinger, Tugs-Saikhan Chimed, Phuong N Le, J Jason Morton, Hilary Somerset, Marileila Varella-Garcia, Aik-Choon Tan, John I Song, Daniel W Bowles, Mary E Reyland, Antonio Jimeno
PURPOSE: Salivary gland cancers (SGC) frequently present with distant metastases many years after diagnosis, suggesting a cancer stem cell (CSC) subpopulation that initiates late recurrences; however current models are limited both in their availability and suitability to characterize these rare cells. EXPERIMENTAL DESIGN: Patient-derived xenografts (PDX) were generated by engrafting patient tissue onto nude mice from one acinic cell carcinoma (AciCC), four adenoid cystic carcinoma (ACC), and three mucoepidermoid carcinoma (MEC) cases, which were derived from successive relapses from the same MEC patient...
March 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Loredana Campo, Eun-Kyoung Breuer
Studies have shown that transforming acidic coiled-coil protein 3 (TACC3), a key component of centrosome-microtubule dynamic networks, is significantly associated with various types of human cancer. We have recently reported that high levels of TACC3 are found in breast cancer, lead to the accumulation of spontaneous DNA damage due to defective DNA damage response signaling, and confer cellular sensitivity to radiation and poly(ADP-ribose) polymerase (PARP) inhibitors. Although our study suggests a potential role of TACC3 as a biomarker in breast cancer detection and prediction of therapy outcome, its role as a therapeutic target in breast cancer is not well studied...
March 16, 2018: Biochemical and Biophysical Research Communications
V Moalic-Allain
Hematopoietic stem cell transplantation is a common procedure potentially beneficial to many individuals with cancer, hematological, or inherited disorders, and has highlighted the need of related or unrelated donors to perform allograft. Donation of hematopoietic stem cells, either through bone marrow harvest or peripheral blood stem cell collection, is well-established and widespread. Over the past two decades, the peripheral blood stem cell collection by aphaeresis has become the main source of hematopoietic stem cells for transplantation, due to faster engraftment and practicability and lower risk of relapse for high-risk patients...
March 16, 2018: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
Mahasweta Gooptu, Haesook T Kim, Vincent T Ho, Edwin P Alyea, John Koreth, Philippe Armand, Jerome Ritz, Sarah Nikiforow, Brett E Glotzbecker, Prashant Nageshwar, Robert J Soiffer, Joseph H Antin, Corey S Cutler
INTRODUCTION: With improvement in transplantation practices in the modern era, non-relapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (HSCT) has improved, while disease relapse rates have remained unchanged. Survival outcomes are therefore driven by NRM in the modern era. Myeloablative conditioning (MAC) regimens are used to maximize disease control and facilitate engraftment; however their use is often limited by toxicity. The commonly used MAC regimens incorporate either chemotherapy plus total body irradiation (TBI) or combination chemotherapy...
March 16, 2018: Biology of Blood and Marrow Transplantation
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