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https://www.readbyqxmd.com/read/27933604/chemoresistant-lung-cancer-stem-cells-display-high-dna-repair-capability-to-remove-cisplatin-dna-damage
#1
Wai-Kin Yu, Zhigang Wang, Chi-Chun Fong, Dandan Liu, Tak-Chun Yip, Siu-Kie Au, Guangyu Zhu, Mengsu Yang
BACKGROUND AND PURPOSE: The persistence of lung cancer stem cells (LCSCs) has been proposed to be the main factor of lung cancer recurrence due to their high resistance to conventional chemotherapy. The underlying mechanisms, however, have not been fully addressed. EXPERIMENTAL APPROACH: In this study, we examined the cellular response of a human lung cancer stem cell line upon treatment with cisplatin, a DNA-damaging anticancer drug that is extensively applied in clinics...
December 9, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27933304/preclinical-validation-lv-il-12-transduction-of-patient-leukemia-cells-for-immunotherapy-of-aml
#2
Ju Huang, Yuanfeng Liu, Bryan C Au, Dwayne L Barber, Andrea Arruda, Axel Schambach, Michael Rothe, Mark D Minden, Christopher J Paige, Jeffrey A Medin
Interleukin-12 (IL-12) is a potent cytokine that may be harnessed to treat cancer. To date, nearly 100 IL-12-based clinical trials have been initiated worldwide. Yet systemic administration of IL-12 is toxic. Different strategies are being developed to reduce such toxicities by restricting IL-12 distribution. Our previous studies employed lentivector-mediated expression of murine IL-12 in tumor cells and demonstrated effective protection in both mouse leukemia and solid tumor challenge models. In this study, we carried out preclinical validation studies using a novel lentivector to engineer expression of human IL-12 in acute myeloid leukemia blast cells isolated from 21 patients...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933271/functional-significance-of-aurora-kinases-p53-protein-family-interactions-in-cancer
#3
REVIEW
Kaori Sasai, Warapen Treekitkarnmongkol, Kazuharu Kai, Hiroshi Katayama, Subrata Sen
Aurora kinases play critical roles in regulating spindle assembly, chromosome segregation, and cytokinesis to ensure faithful segregation of chromosomes during mitotic cell division cycle. Molecular and cell biological studies have revealed that Aurora kinases, at physiological levels, orchestrate complex sequential cellular processes at distinct subcellular locations through functional interactions with its various substrates. Aberrant expression of Aurora kinases, on the other hand, cause defects in mitotic spindle assembly, checkpoint response activation, and chromosome segregation leading to chromosomal instability...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27932791/migration-and-invasion-of-drug-resistant-lung-adenocarcinoma-cells-are-dependent-on-mitochondrial-activity
#4
Ji Hoon Jeon, Dong Keon Kim, Youngmi Shin, Hee Yeon Kim, Bomin Song, Eun Young Lee, Jong Kwang Kim, Hye Jin You, Heesun Cheong, Dong Hoon Shin, Seong-Tae Kim, Jae-Ho Cheong, Soo Youl Kim, Hyonchol Jang
A small proportion of cancer cells have stem-cell-like properties, are resistant to standard therapy and are associated with a poor prognosis. The metabolism of such drug-resistant cells differs from that of nearby non-resistant cells. In this study, the metabolism of drug-resistant lung adenocarcinoma cells was investigated. The expression of genes associated with oxidative phosphorylation in the mitochondrial membrane was negatively correlated with the prognosis of lung adenocarcinoma. Because the mitochondrial membrane potential (MMP) reflects the functional status of mitochondria and metastasis is the principal cause of death due to cancer, the relationship between MMP and metastasis was evaluated...
December 9, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27932755/-effects-of-apigenin-on-self-renewal-and-%C3%A2-upar-expression-in-nci-h446-cell-line
#5
Ling Shu, Qing Yuan, Yinghong Cui, Shuwen Sun, A Chen, Dan Chen, Jianguo Cao, Jiansong Zhang
To investigate the effect of apigenin on self-renewal for sphere-forming cells in human small cell lung cancer cell line NCI-H446 and the underlying mechanisms.
 Methods: Sphere-forming cells from NCI-H446 cell line were cultured in stem cell-conditioned culture medium with ultra-low attachment surface plates. The rate of sphere-forming cells in the second passage sphere-forming cells was used to evaluate the inhibitory effects of apigenin on the self-renewal for sphere-forming cells. The protein level of urokinase-type plasminogen activator receptor (uPAR) in spheroids was analyzed by Western blot...
November 28, 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/27932483/roles-and-regulations-of-the-ets-transcription-factor-elf4-mef
#6
REVIEW
Mary Ann Suico, Tsuyoshi Shuto, Hirofumi Kai
Most E26 transformation-specific (ETS) transcription factors are involved in the pathogenesis and progression of cancer. This is in part due to the roles of ETS transcription factors in basic biological processes such as growth, proliferation, and differentiation, and also because of their regulatory functions that have physiological relevance in tumorigenesis, immunity, and basal cellular homoeostasis. A member of the E74-like factor (ELF) subfamily of the ETS transcription factor family-myeloid elf-1-like factor (MEF), designated as ELF4-has been shown critically involved in immune response and signalling, osteogenesis, adipogenesis, cancer, and stem cell quiescence...
December 8, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27932422/significance-of-low-mtorc1-activity-in-defining-the-characteristics-of-brain-tumor-stem-cells
#7
Yi-Peng Han, Atsushi Enomoto, Yukihiro Shiraki, Shen-Qi Wang, Xiaoze Wang, Shinya Toyokuni, Naoya Asai, Kaori Ushida, Hosne Ara, Fumiharu Ohka, Toshihiko Wakabayashi, Jie Ma, Atsushi Natsume, Masahide Takahashi
BACKGROUND: The significance of mammalian target of rapamycin complex 1 (mTORC1) activity in the maintenance of cancer stem cells (CSCs) remains controversial. Previous findings showed that mTORC1 activation depleted the population of leukemia stem cells in leukemia, while maintaining the stemness in pancreatic CSCs. The purpose of this study was to examine the currently unknown role and significance of mTORC1 activity in brain tumor stem cells (BTSCs). METHODS: Basal mTORC1 activity and its kinetics were investigated in BTSC clones isolated from patients with glioblastoma and their differentiated progenies (DIFFs)...
December 8, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27932392/digital-gene-expression-profiling-analysis-of-dna-repair-pathways-in-colon-cancer-stem-population-of-ht29-cells
#8
Wenxue Wang, Guoxiu Zhang, Jing Yang, Huan Gu, Lei Ding, Haijing Yu, Min Yu, Qinghua Cui, Xinglai Ji, Meizhang Li
Cancer stem cells (CSCs) contribute to the relapse and development of new neoplasm lesions. While most available clinical approaches, such as chemical and radiation therapies, will kill the majority of cancer cells, they do not kill them all. Some resisting cells, like CSCs, are able to survive due to their excellent self-maintaining capabilities, even in challenging environments. In the present study, we investigated the mRNA level of DNA repair genes of colon CSCs from the HT29 cell line in response to single-strand damage and double-strand breaks, as well as the evident upregulation of key genes in base excision repair, mismatch repair, non-homologous end-joining, and homologous recombination pathways in these cells...
December 7, 2016: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/27932253/regulation-of-cyclin-d1-by-arsenic-and-microrna-inhibits-adipogenesis
#9
Kevin Beezhold, Linda R Klei, Aaron Barchowsky
Low-dose chronic exposure to arsenic in drinking water represents a global public health concern with established risks for metabolic and cardiovascular disease, as well as cancer. While the linkage between arsenic and disease is strong, further understanding of the molecular mechanisms of its pathogenicity is required. Previous reports demonstrated the ability of arsenic to interfere with adipogenesis, which may mediate its effects in promoting metabolic disease. We hypothesized that microRNA are important regulators of most if not all mesenchymal stem cell processes that are dysregulated by arsenic exposure to impair lipogenesis...
December 5, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27931121/a-new-phenolic-glycoside-from-the-stem-of-dendrobium-nobile
#10
Xue-Ming Zhou, Cai-Juan Zheng, Jia-Ting Wu, Guang-Ying Chen, Bin Zhang, Chong-Ge Sun
A new phenolic glycoside dendroside (1), together with seven known compounds (2-8) were isolated from the stems of Dendrobium nobile. The structures of these compounds were elucidated using comprehensive spectroscopic methods. The inhibitory activities of all compounds against three cancer cell lines HeLa, MCF-7 and A549 were evaluated.
December 8, 2016: Natural Product Research
https://www.readbyqxmd.com/read/27931044/prognostic-impact-of-cd44-positive-cancer-stem-like-cells-at-the-invasive-front-of-gastric-cancer
#11
Hirokazu Kodama, Satoshi Murata, Mitsuaki Ishida, Hiroshi Yamamoto, Tsuyoshi Yamaguchi, Sachiko Kaida, Tohru Miyake, Katsushi Takebayashi, Ryoji Kushima, Masaji Tani
BACKGROUND: The invasive tumour front may provide prognostic information. We examined the relationship between the presence of cancer stem cells (CSCs) at the invasive tumour front and prognosis in gastric cancer (GC). METHODS: CD44 is a CSC marker; accordingly, CD44 standard (CD44s), CD44 variant-6 (CD44v6), and CD44 variant-9 (CD44v9) expression were examined in 123 resected primary GCs and the clinical significance of CSCs at the invasive tumour front was analysed...
December 8, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27930406/stress-response-protein-rbm3-promotes-the-development-of-colitis-associated-cancer
#12
Toshiharu Sakurai, Hiroshi Kashida, Yoriaki Komeda, Tomoyuki Nagai, Satoru Hagiwara, Tomohiro Watanabe, Masayuki Kitano, Naoshi Nishida, Jun Fujita, Masatoshi Kudo
BACKGROUND: Colitis-associated cancer (CAC) is caused by chronic intestinal inflammation and often results from refractory inflammatory bowel disease (IBD). Stress response proteins Cirp and HSPA4 are involved in the refractory clinical course and development of CAC. RNA-binding motif protein 3 (RBM3) is induced in response to various stresses and is upregulated in several cancers. However, the role of RBM3 in CAC is unclear. METHODS: We assessed RBM3 expression and function in 263 human intestinal mucosa samples from patients with IBD and in Rbm3-deficient (Rbm3) mice...
December 7, 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27930300/an-nad-dependent-transcriptional-program-governs-self-renewal-and-radiation-resistance-in-glioblastoma
#13
Amit D Gujar, Son Le, Diane D Mao, David Y A Dadey, Alice Turski, Yo Sasaki, Diane Aum, Jingqin Luo, Sonika Dahiya, Liya Yuan, Keith M Rich, Jeffrey Milbrandt, Dennis E Hallahan, Hiroko Yano, David D Tran, Albert H Kim
Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD(+)). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD(+) synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival...
December 7, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27930094/cancer-stem-cell-hypothesis-for-therapeutic-innovation-in-clinical-oncology-taking-the-root-out-not-chopping-the-leaf
#14
Kevin Dzobo, Dimakatso Alice Senthebane, Arielle Rowe, Nicholas Ekow Thomford, Lamech M Mwapagha, Nasir Al-Awwad, Collet Dandara, M Iqbal Parker
Clinical oncology is in need of therapeutic innovation. New hypotheses and concepts for translation of basic research to novel diagnostics and therapeutics are called for. In this context, the cancer stem cell (CSC) hypothesis rests on the premise that tumors comprise tumor cells and a subset of tumor-initiating cells, CSCs, in a quiescent state characterized by slow cell cycling and expression of specific stem cell surface markers with the capability to maintain a tumor in vivo. The CSCs have unlimited self-renewal abilities and propagate tumors through division into asymmetric daughter cells...
December 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27929731/autophagic-homeostasis-is-required-for-the-pluripotency-of-cancer-stem-cells
#15
Tanveer Sharif, Emma Martell, Cathleen Dai, Barry E Kennedy, Patrick Murphy, Derek Clements, Youra Kim, Patrick W K Lee, Shashi Gujar
Pluripotency is an important feature of cancer stem cells (CSCs) that contributes to self-renewal and chemoresistance. The maintenance of pluripotency of CSCs under various pathophysiological conditions requires a complex interaction between various cellular pathways including those involved in homeostasis and energy metabolism. However, the exact mechanisms that maintain the CSC pluripotency remain poorly understood. In this report, using both human and murine models of CSCs, we demonstrate that basal levels of autophagy are required to maintain the pluripotency of CSCs, and that this process is differentially regulated by the rate limiting enzyme in the NAD(+) synthesis pathway NAMPT (nicotinamide phosphoribosyltransferase) and the transcription factor POU5F1/OCT4 (POU class 5 homeobox 1)...
December 8, 2016: Autophagy
https://www.readbyqxmd.com/read/27929108/human-adipose-mesenchymal-stem-cell-derived-exosomal-mirnas-are-critical-factors-for-inducing-anti-proliferation-signalling-to-a2780-and-skov-3-ovarian-cancer-cells
#16
Abu Musa Md Talimur Reza, Yun-Jung Choi, Hideyo Yasuda, Jin-Hoi Kim
An enigmatic question exists concerning the pro- or anti-cancer status of mesenchymal stem cells (MSCs). Despite growing interest, this question remains unanswered, and the debate became intensified with new evidences backing each side. Here, we showed that human adipose MSC (hAMSC)-derived conditioned medium (CM) exhibited inhibitory effects on A2780 human ovarian cancer cells by blocking the cell cycle, and activating mitochondria-mediated apoptosis signalling. Explicitly, we demonstrated that exosomes, an important biological component of hAMSC-CM, could restrain proliferation, wound-repair and colony formation ability of A2780 and SKOV-3 cancer cells...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27928465/gene-expression-and-pathway-analysis-of-ctnnb1-in-cancer-and-stem-cells
#17
Shihori Tanabe, Takeshi Kawabata, Kazuhiko Aoyagi, Hiroshi Yokozaki, Hiroki Sasaki
AIM: To investigate β-catenin (CTNNB1) signaling in cancer and stem cells, the gene expression and pathway were analyzed using bioinformatics. METHODS: The expression of the catenin β 1 (CTNNB1) gene, which codes for β-catenin, was analyzed in mesenchymal stem cells (MSCs) and gastric cancer (GC) cells. Beta-catenin signaling and the mutation of related proteins were also analyzed using the cBioPortal for Cancer Genomics and HOMology modeling of Complex Structure (HOMCOS) databases...
November 26, 2016: World Journal of Stem Cells
https://www.readbyqxmd.com/read/27927847/preserved-seminiferous-tubule-integrity-with-spermatogonial-survival-and-induction-of-sertoli-and-leydig-cell-maturation-after-long-term-organotypic-culture-of-prepubertal-human-testicular-tissue
#18
F de Michele, J Poels, L Weerens, C Petit, Z Evrard, J Ambroise, D Gruson, C Wyns
STUDY QUESTION: Is an organotypic culture system able to provide the appropriate testicular microenvironment for in-vitro maturation of human immature testicular tissue (ITT)? SUMMARY ANSWER: Our organotypic culture system provided a microenvironment capable of preserving seminiferous tubule (ST) integrity and Leydig cell (LC) functionality and inducing Sertoli cell (SC) maturation. WHAT IS KNOWN ALREADY: Cryopreservation of human ITT is a well-established strategy to preserve fertility in prepubertal boys affected by cancer, with a view for obtaining sperm...
December 6, 2016: Human Reproduction
https://www.readbyqxmd.com/read/27927750/mdm2-as-a-chromatin-modifier
#19
REVIEW
Magdalena Wienken, Ute M Moll, Matthias Dobbelstein
Mdm2 is the key negative regulator of the tumour suppressor p53, making it an attractive target for anti-cancer drug design. We recently identified a new role of Mdm2 in gene repression through its direct interaction with several proteins of the polycomb group (PcG) family. PcG proteins form polycomb repressive complexes PRC1 and PRC2. PRC2 (via EZH2) mediates histone 3 lysine 27 (H3K27) trimethylation, and PRC1 (via RING1B) mediates histone 2A lysine 119 (H2AK119) monoubiquitination. Both PRCs mostly support a compact and transcriptionally silent chromatin structure...
November 9, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27927191/somatostatin-signaling-via-sstr1-contributes-to-the-quiescence-of-colon-cancer-stem-cells
#20
Shirin R Modarai, Lynn M Opdenaker, Vignesh Viswanathan, Jeremy Z Fields, Bruce M Boman
BACKGROUND: Neuroendocrine cells (NECs) reside adjacent to colonic stem cells (SCs) in the crypt stem cell (SC) niche, but how NECs are involved in regulation of SCs is unclear. We investigated NECs expressing somatostatin (SST) and somatostatin receptor type 1 (SSTR1) because SST inhibits intestinal proliferation. HYPOTHESIS: SSTR1 cells maintain SCs in a quiescent state, and aberrant SST signaling contributes to SC overpopulation in colorectal cancer (CRC). METHODS: The proportion of SCs to NECs cells was quantified, by flow cytometry, in CRC cell lines and primary normal/tumor tissues based on cellular ALDH and SSTR1 levels, respectively...
December 7, 2016: BMC Cancer
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