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https://www.readbyqxmd.com/read/28449469/cd90-positive-cells-exhibit-aggressive-radioresistance-in-esophageal-squamous-cell-carcinoma
#1
Yuandong Wang, Chi Zhang, Hongcheng Zhu, Junwei Tang, Shu Zhang, Jinhua Luo, Xinchen Sun
BACKGROUND: Cancer stem cells (CSCs) are widely abundant and considered to be an important factor in therapy resistance. They are also promising potential targets for conquering tumors. We explored the effects of radiation on stem cell-like tumor cells via the candidate marker CD90 to provide new ideas for the comprehensive treatment of esophageal squamous cell carcinoma (ESCC). METHODS: We constructed CD90 overexpression ESCC cells by lentiviral transfection and observed differences of toxicity, proliferation, clone number, apoptosis, migration, invasion, and in vivo tumor formation after irradiation...
March 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28446688/transient-cdk4-6-inhibition-protects-hematopoietic-stem-cells-from-chemotherapy-induced-exhaustion
#2
Shenghui He, Patrick J Roberts, Jessica A Sorrentino, John E Bisi, Hannah Storrie-White, Renger G Tiessen, Karenann M Makhuli, William A Wargin, Henko Tadema, Ewoud-Jan van Hoogdalem, Jay C Strum, Rajesh Malik, Norman E Sharpless
Conventional cytotoxic chemotherapy is highly effective in certain cancers but causes dose-limiting damage to normal proliferating cells, especially hematopoietic stem and progenitor cells (HSPCs). Serial exposure to cytotoxics causes a long-term hematopoietic compromise ("exhaustion"), which limits the use of chemotherapy and success of cancer therapy. We show that the coadministration of G1T28 (trilaciclib), which is a small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), contemporaneously with cytotoxic chemotherapy protects murine hematopoietic stem cells (HSCs) from chemotherapy-induced exhaustion in a serial 5-fluorouracil treatment model...
April 26, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28446230/label-retention-and-stem-cell-marker-expression-in-the-developing-and-adult-prostate-identifies-basal-and-luminal-epithelial-stem-cell-subpopulations
#3
Jens Adam Ceder, Tilly Wilhelmina Aalders, Jack Antonius Schalken
BACKGROUND: Prostate cancer is the second most frequent cancer among males worldwide, and most patients with metastatic disease eventually develop therapy-resistant disease. Recent research has suggested the existence of cancer stem-like cells, and that such cells are behind the therapy resistance and progression. METHODS: Here, we have taken advantage of the relatively quiescent nature of stem cells to identify the slow-cycling label-retaining stem cell (LRC) populations of the prostate gland...
April 26, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28446006/trending-speculations-of-tumor-initiating-cells-in-squamous-cell-cancers-of-head-and-neck
#4
REVIEW
Wasim Kamate, Rajendra Baad, Nupura Vibhute, Uzma Belgaumi, Vidya Kadashetti, Sushma Gugwad
Tumor-initiating cells are a diminutive subpopulation of stem cells that have ability of long term self-renewal and generation of varied traits of tumor cell population. Understanding the concept of tumor-initiating cells may have a great implicative intimation for our comprehension of cancer pathobiology and for the delineation of new therapies directed towards these stem cells. The present review is an endeavor to conceptualize the role of tumor-initiating cells in the Squamous Cell Cancers (SCC) of head and neck, their role in tumorigenesis and the possible supplementary approach in the latest treatment modalities...
April 30, 2017: International Journal of Stem Cells
https://www.readbyqxmd.com/read/28445466/human-pluripotent-stem-cells-recurrently-acquire-and-expand-dominant-negative-p53-mutations
#5
Florian T Merkle, Sulagna Ghosh, Nolan Kamitaki, Jana Mitchell, Yishai Avior, Curtis Mello, Seva Kashin, Shila Mekhoubad, Dusko Ilic, Maura Charlton, Genevieve Saphier, Robert E Handsaker, Giulio Genovese, Shiran Bar, Nissim Benvenisty, Steven A McCarroll, Kevin Eggan
Human pluripotent stem cells (hPS cells) can self-renew indefinitely, making them an attractive source for regenerative therapies. This expansion potential has been linked with the acquisition of large copy number variants that provide mutated cells with a growth advantage in culture. The nature, extent and functional effects of other acquired genome sequence mutations in cultured hPS cells are not known. Here we sequence the protein-coding genes (exomes) of 140 independent human embryonic stem cell (hES cell) lines, including 26 lines prepared for potential clinical use...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28445439/her2-in-breast-cancer-stemness-a-negative-feedback-loop-towards-trastuzumab-resistance
#6
REVIEW
Babak Nami, Zhixiang Wang
HER2 receptor tyrosine kinase that is overexpressed in approximately 20% of all breast cancers (BCs) is a poor prognosis factor and a precious target for BC therapy. Trastuzumab is approved by FDA to specifically target HER2 for treating HER2+ BC. However, about 60% of patients with HER2+ breast tumor develop de novo resistance to trastuzumab, partially due to the loss of expression of HER2 extracellular domain on their tumor cells. This is due to shedding/cleavage of HER2 by metalloproteinases (ADAMs and MMPs)...
April 26, 2017: Cancers
https://www.readbyqxmd.com/read/28445002/glucose-metabolism-targeting-therapy-and-withaferin-a-are-effective-for-egfr-tki-induced-drug-tolerant-persisters
#7
Kei Kunimasa, Tatsuya Nagano, Yohei Shimono, Ryota Dokuni, Tatsunori Kiriu, Shuntaro Tokunaga, Daisuke Tamura, Masatsugu Yamamoto, Motoko Tachihara, Kazuyuki Kobayashi, Miyako Satouchi, Yoshihiro Nishimura
In pathway-targeted cancer drug therapies, the relatively rapid emergence of drug-tolerant persisters (DTPs) substantially limits the overall therapeutic benefit. However, little is known about the roles of DTPs in drug resistance. In this study, we investigated the features of EGFR-TKI induced DTPs and explored a new treatment strategy to overcome the emergence of these DTPs. We used two EGFR mutated lung adenocarcinoma cell lines, PC9 and II-18. They were treated with 2 μM gefitinib for 6, 12, or 24 days or 6 month...
April 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28442534/oncogenic-%C3%AE-catenin-and-pik3ca-instruct-network-states-and-cancer-phenotypes-in-intestinal-organoids
#8
Pamela Riemer, Mattias Rydenfelt, Matthias Marks, Karen van Eunen, Kathrin Thedieck, Bernhard G Herrmann, Nils Blüthgen, Christine Sers, Markus Morkel
Colorectal cancer is driven by cooperating oncogenic mutations. In this study, we use organotypic cultures derived from transgenic mice inducibly expressing oncogenic β-catenin and/or PIK3CA(H1047R) to follow sequential changes in cancer-related signaling networks, intestinal cell metabolism, and physiology in a three-dimensional environment mimicking tissue architecture. Activation of β-catenin alone results in the formation of highly clonogenic cells that are nonmotile and prone to undergo apoptosis. In contrast, coexpression of stabilized β-catenin and PIK3CA(H1047R) gives rise to intestinal cells that are apoptosis-resistant, proliferative, stem cell-like, and motile...
April 25, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28442393/progesterone-receptors-pr-mediate-stat-actions-pr-and-prolactin-receptor-signaling-crosstalk-in-breast-cancer-models
#9
Katherine A Leehy, Thu H Truong, Laura J Mauro, Carol A Lange
Estrogen is the major mitogenic stimulus of mammary gland development during puberty wherein ER signaling acts to induce abundant PR expression. PR signaling, in contrast, is the primary driver of mammary epithelial cell proliferation in adulthood. The high circulating levels of progesterone during pregnancy signal through PR, inducing expression of the prolactin receptor (PRLR). Cooperation between PR and prolactin (PRL) signaling, via regulation of downstream components in the PRL signaling pathway including JAKs and STATs, facilitates the alveolar morphogenesis observed during pregnancy...
April 22, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28441730/regulatory-mirnas-in-colorectal-carcinogenesis-and-metastasis
#10
REVIEW
Yongchen Guo, Yonghua Bao, Wancai Yang
Colorectal cancer is one of the most common malignancies and is the second-leading cause of cancer-related death world-wide, which is linked to genetic mutations, epigenetic alterations, and oncogenic signaling activation. MicroRNAs, one of the categories of epigenetics, have been demonstrated significant roles in carcinogenesis and progression through regulating of oncogenic signaling pathways, stem cells, epithelial-mesenchymal transition, and metastasis. This review summarizes the roles of microRNAs in the regulating of Wnt, Ras, TGF-β, and inflammatory signaling pathways, stemness, and epithelial-mesenchymal transition, for carcinogenesis and metastasis in colorectal cancer...
April 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28440478/overexpression-of-secretory-phospholipase-a2-iia-supports-cancer-stem-cell-phenotype-via-her-erbb-elicited-signaling-in-lung-and-prostate-cancer-cells
#11
Shan Lu, Zhongyun Dong
Resistance to conventional chemotherapies remains a significant clinical challenge in treatment of cancer. The cancer stem cells (CSCs) have properties necessary for tumor initiation, resistance to therapy, and progression. HER/ERBB‑elicited signaling supports CSC properties. Our previous studies revealed that secretory phospholipase A2 group IIa (sPLA2‑IIa) is overexpressed in both prostate and lung cancer cells, leading to an aberrant high level in the interstitial fluid, i.e., tumor microenvironment and blood...
April 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28440445/mir%C3%A2-196a%C3%A2-5p-modulates-gastric-cancer-stem-cell-characteristics-by-targeting-smad4
#12
Yunzhi Pan, Xiong Shu, Lichao Sun, Long Yu, Lixin Sun, Zhihua Yang, Yuliang Ran
Cancer stem cells (CSCs) are undifferentiated cancer cells with a high tumorigenic activity, the ability to undergo self-renewal, and a multilineage differentiation potential. Clinical evidence suggests that CSCs in a tumor mass are the cellular determinants to promote cancer invasion and metastasis. MicroRNAs (miRNAs) have emerged as important modulators of cancer stem cell characteristics. Unveiling the candidate miRNAs that regulate CSCs may provide novel therapeutic targets against cancer. We analyzed the miRNA expression profiles regulating the cancer stem-like cell characteristics in gastric cancer...
April 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28439492/leptin-signaling-and-cancer-chemoresistance-perspectives
#13
EDITORIAL
Pierre V Candelaria, Antonio Rampoldi, Adriana Harbuzariu, Ruben R Gonzalez-Perez
Obesity is a major health problem and currently is endemic around the world. Obesity is a risk factor for several different types of cancer, significantly promoting cancer incidence, progression, poor prognosis and resistance to anti-cancer therapies. The study of this resistance is critical as development of chemoresistance is a serious drawback for the successful and effective drug-based treatments of cancer. There is increasing evidence that augmented adiposity can impact on chemotherapeutic treatment of cancer and the development of resistance to these treatments, particularly through one of its signature mediators, the adipokine leptin...
April 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28436991/crb3-downregulation-confers-breast-cancer-stem-cell-traits-through-taz-%C3%AE-catenin
#14
P Li, Y Wang, X Mao, Y Jiang, J Liu, J Li, J Wang, R Wang, J She, J Zhang, J Yang, Y Liu, P Liu
The cancer stem cell (CSC) theory depicts a special population within the cancer mass that self-renew and sustain the cancer, even if the other cells were eliminated by therapies. How CSCs acquire these unique traits is still unclear. Crumbs homolog 3 (CRB3), a member of the CRB polarity complex, has been reported to act as a tumor suppressor. Here, we detected significantly lower or negative CRB3 expression in human breast cancer tissues. Knockdown of CRB3 generated non-tumorigenic, immortalized breast epithelial cell line MCF 10A with CSC properties...
April 24, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28435473/downregulation-of-mitochondrial-cyclooxygenase-2-inhibits-the-stemness-of-nasopharyngeal-carcinoma-by-decreasing-the-activity-of-dynamin-related-protein-1
#15
Teng-Jian Zhou, Shi-Li Zhang, Cheng-Yong He, Qun-Ying Zhuang, Pei-Yu Han, Sheng-Wei Jiang, Huan Yao, Yi-Jun Huang, Wen-Hua Ling, Yu-Chun Lin, Zhong-Ning Lin
Cancer stem cells (CSCs) are a small subset of malignant cells, possessing stemness, with strong tumorigenic capability, conferring resistance to therapy and leading to the relapse of nasopharyngeal carcinoma (NPC). Our previous study suggested that cyclooxygenase-2 (COX-2) would be a novel target for the CSCs-like side population (SP) cells in NPC. In the present study, we further found that COX-2 maintained the stemness of NPC by enhancing the activity of mitochondrial dynamin-related protein 1 (Drp1), a mitochondrial fission mediator, by studying both sorted SP cells from NPC cell lines and gene expression analyses in NPC tissues...
2017: Theranostics
https://www.readbyqxmd.com/read/28435069/age-related-increase-in-wnt-inhibitor-causes-a-senescence-like-phenotype-in-human-cardiac-stem-cells
#16
Tamami Nakamura, Tohru Hosoyamaa, Junichi Murakami, Makoto Samura, Koji Ueno, Hiroshi Kurazumi, Ryo Suzuki, Akihito Mikamo, Kimikazu Hamano
Aging of cardiac stem/progenitor cells (CSCs) impairs heart regeneration and leads to unsatisfactory outcomes of cell-based therapies. As the precise mechanisms underlying CSC aging remain unclear, the use of therapeutic strategies for elderly patients with heart failure is severely delayed. In this study, we used human cardiosphere-derived cells (CDCs), a subtype of CSC found in the postnatal heart, to identify secreted factor(s) associated with CSC aging. Human CDCs were isolated from heart failure patients of various ages (2-83 years old)...
April 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28435061/nanomedicine-mediated-drug-targeting-of-cancer-stem-cells
#17
REVIEW
Deepika Singh, Aliva Prity Minz, Sanjeeb Kumar Sahoo
Tumors are heterogeneous and contain a small population of cells that has a crucial role in tumor progression, metastasis, drug resistance, and relapse as a result of their self-renewal, proliferation, and differentiation properties. These cells are known as cancer stem cells (CSCs) and accumulating evidence suggests that they show significant resistance to conventional chemotherapy. Thus, various antitumor strategies have been developed to eliminate therapeutic-resistant CSCs by targeting the molecular differences between CSCs and bulk cancer cells...
April 20, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28433655/targeting-sarcoma-tumor-initiating-cells-through-differentiation-therapy
#18
Dan Han, Veronica Rodriguez-Bravo, Elizabeth Charytonowicz, Elizabeth Demicco, Josep Domingo-Domenech, Robert G Maki, Carlos Cordon-Cardo
Human leukocyte antigen class I (HLA-I) down-regulation has been reported in many human cancers to be associated with poor clinical outcome. However, its connection to tumor-initiating cells (TICs) remains unknown. In this study, we report that HLA-I is down-regulated in a subpopulation of cells that have high tumor initiating capacity in different types of human sarcomas. Detailed characterization revealed their distinct molecular profiles regarding proliferation, apoptosis and stemness programs. Notably, these TICs can be induced to differentiate along distinct mesenchymal lineages, including the osteogenic pathway...
April 13, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28432589/expression-and-function-of-abcg2-and-xiap-in-glioblastomas
#19
Ivette F Emery, Archana Gopalan, Stephanie Wood, Kin-Hoe Chow, Chiara Battelli, Joshy George, Hagen Blaszyk, Jeffrey Florman, Kyuson Yun
Despite multimodal treatment that includes surgery, radiation and chemotherapy, virtually all glioblastomas (GBM) recur, indicating that these interventions are insufficient to eradicate all malignant cells. To identify potential new therapeutic targets in GBMs, we examined the expression and function of proteins that are associated with therapy resistance and cancer cell survival. We measured the expression of eight such proteins in 50 GBM samples by immunohistochemistry and analyzed patient survival. We report that GBM patients with high expression of ABCG2 (also called BCRP) or XIAP at the protein level had worse survival than those with low expression...
April 21, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28430641/the-regulation-of-%C3%AE-catenin-activity-and-function-in-cancer-therapeutic-opportunities
#20
REVIEW
Shuang Shang, Fang Hua, Zhuo-Wei Hu
Wnt/β-catenin signaling is an evolutionarily conserved and versatile pathway that is known to be involved in embryonic development, tissue homeostasis and a wide variety of human diseases. Aberrant activation of this pathway gives rise to the accumulation of β-catenin in the nucleus and promotes the transcription of many oncogenes such as c-Myc and CyclinD-1. As a result, it contributes to carcinogenesis and tumor progression of several cancers, including colon cancer, hepatocellular carcinoma, pancreatic cancer, lung cancer and ovarian cancer...
February 25, 2017: Oncotarget
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