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https://www.readbyqxmd.com/read/28441528/phosphorylation-of-neurog3-links-endocrine-differentiation-to-the-cell-cycle-in-pancreatic-progenitors
#1
Nicole A J Krentz, Dennis van Hoof, Zhongmei Li, Akie Watanabe, Mei Tang, Cuilan Nian, Michael S German, Francis C Lynn
During pancreatic development, proliferating pancreatic progenitors activate the proendocrine transcription factor neurogenin 3 (NEUROG3), exit the cell cycle, and differentiate into islet cells. The mechanisms that direct robust NEUROG3 expression within a subset of progenitor cells control the size of the endocrine population. Here we demonstrate that NEUROG3 is phosphorylated within the nucleus on serine 183, which catalyzes its hyperphosphorylation and proteosomal degradation. During progression through the progenitor cell cycle, NEUROG3 phosphorylation is driven by the actions of cyclin-dependent kinases 2 and 4/6 at G1/S cell-cycle checkpoint...
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28440912/performance-of-in-silico-tools-for-the-evaluation-of-p16ink4a-cdkn2a-variants-in-cagi
#2
Marco Carraro, Giovanni Minervini, Manuel Giollo, Yana Bromberg, Emidio Capriotti, Rita Casadio, Roland Dunbrack, Lisa Elefanti, Pietro Fariselli, Carlo Ferrari, Julian Gough, Panagiotis Katsonis, Emanuela Leonardi, Olivier Lichtarge, Chiara Menin, Pier Luigi Martelli, Abhishek Niroula, Lipika R Pal, Susanna Repo, Maria Chiara Scaini, Mauno Vihinen, Qiong Wei, Qifang Xu, Yuedong Yang, Yizhou Yin, Jan Zaucha, Huiying Zhao, Yaoqi Zhou, Steven E Brenner, John Moult, Silvio C E Tosatto
Correct phenotypic interpretation of variants of unknown significance for cancer-associated genes is a diagnostic challenge as genetic screenings gain in popularity in the next-generation sequencing era. The Critical Assessment of Genome Interpretation (CAGI) experiment aims to test and define the state of the art of genotype-phenotype interpretation. Here, we present the assessment of the CAGI p16INK4a challenge. Participants were asked to predict the effect on cellular proliferation of ten variants for the p16INK4a tumor suppressor, a cyclin-dependent kinase inhibitor encoded by the CDKN2A gene...
April 25, 2017: Human Mutation
https://www.readbyqxmd.com/read/28440486/synergistic-antitumor-effects-of-cdk-inhibitor-sns%C3%A2-032-and-an-oncolytic-adenovirus-co%C3%A2-expressing-trail-and-smac-in-pancreatic-cancer
#3
Yun Ge, Wen Lei, Yingyu Ma, Yigang Wang, Buyun Wei, Xiaoyi Chen, Guoqing Ru, Xianglei He, Xiaozhou Mou, Shibing Wang
Gene therapy using oncolytic adenoviruses is a novel approach for human cancer therapeutics. The current study aimed to investigate whether the combined use of an adenovirus expressing tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) and second mitochondria‑derived activator of caspase (Smac) upon caspase activation (ZD55‑TRAIL‑IETD‑Smac) and cyclin‑dependent kinase (CDK) inhibitor SNS‑032 will synergistically reinforce their anti‑pancreatic cancer activities. The experiments in vitro demonstrated that SNS‑032 enhances ZD55‑TRAIL‑IETD‑Smac‑induced apoptosis and causes marked pancreatic cancer cell death...
April 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440465/5-furan-2-yl-4-3-4-5-trimethoxyphenyl-3h-1-2-dithiol-3-one-oxime-6f-a-new-synthetic-compound-causes-human-%C3%AF-brosarcoma-ht-1080-cell-apoptosis-by-disrupting-tubulin-polymerisation-and-inducing-g2-m-arrest
#4
Daiying Zuo, Lili Pang, Jiwei Shen, Qi Guan, Zhaoshi Bai, Huijuan Zhang, Yao Li, Guodong Lu, Weige Zhang, Yingliang Wu
In the current study, we synthesized a series of new compounds targeting tubulin and tested their anti-proliferative activities. Among these new synthetic com-pounds, 5-(furan-2-yl)-4-(3,4,5-trimethoxyphenyl)-3H-1,2-dithiol-3-one oxime (6f) exhibited significant anti-proliferative activity against different human cancer cell lines including human gastric adenocarcinoma SGC-7901, human non-small cell lung cancer A549, and human fibrosarcoma HT-1080. As a result, 6f was selected to further test the sensitivity to different cancer cell lines including human cervical cancer cell line HeLa, human breast cancer cell line MCF-7, non-small cell lung cancer cell line A549, human liver carcinoma cell line HepG-2, human oral squamous cell carcinoma cell lines KB, SGC-7901 and HT-1080...
April 18, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28440462/imperatorin-efficiently-blocks-tnf-%C3%AE-mediated-activation-of-ros-pi3k-akt-nf-%C3%AE%C2%BAb-pathway
#5
Ke Si Wang, Ying Lv, Zhe Wang, Juan Ma, Chunliu Mi, Xuezheng Li, Guang Hua Xu, Lian Xun Piao, Sheng Zhe Zheng, Xuejun Jin
Inflammation contributes to development and progression in a variety of cancers, including cervical cancer, which is the second leading cause of cancer deaths in women worldwide. In this study, we examined the anti-inflammatory effects of imperatorin, a psoralen-type furanocoumarin from the fruits of Angelica dahurica, in tumor necrosis factor-α (TNF-α)-stimulated HeLa cells by investigating its impact on the production and expression of cytokines and the major signal-transduction pathways. We found this compound significantly inhibited the TNF-α-induced expression of NF-κB target genes, such as COX-2, cyclin  D1, MMP-9, VEGF, IL-6 and Bcl-xL in a concentration-dependent manner...
April 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440426/downregulation-of-microrna-30d-promotes-cell-proliferation-and-invasion-by-targeting-lrh-1-in-colorectal-carcinoma
#6
Likun Yan, Jian Qiu, Jianfeng Yao
The aberrant expression of miR-30d has been reported in several types of human malignancies. However, its biological function in colorectal cancer (CRC) remains largely unknown. In this study, we identified that miR‑30d was significantly downregulated in CRC tissues compared to that observed in normal controls as detected by RT‑qPCR analysis. Downregulation of miR‑30d was significantly associated with aggressive clinicopathological parameters including tumor differentiation, invasive depth, TNM stage, lymph node metastasis, distant metastasis, and poor prognosis...
April 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28440424/therapeutic-potential-of-the-antidiabetic-drug-metformin-in-small-bowel-adenocarcinoma
#7
Taiga Chiyo, Kiyohito Kato, Hisakazu Iwama, Shintaro Fujihara, Koji Fujita, Tomoko Tadokoro, Kyoko Ohura, Eri Samukawa, Yoshimi Yamana, Nobuya Kobayashi, Tae Matsunaga, Noriko Nishiyama, Maki Ayaki, Tatsuo Yachida, Asahiro Morishita, Hideki Kobara, Hirohito Mori, Tsutomu Masaki
Small bowel adenocarcinoma (SBAC) accounts for 3% of all gastrointestinal tract tumors and approximately 0.5% of all cancer cases. Recent studies have indicated that the use of metformin, one of the most commonly prescribed antidiabetic drugs, is associated with a better prognosis for certain malignant diseases. However, there have been no reports on the effect of metformin in SBAC. In the present study, we evaluated the effect of metformin on human SBAC cell proliferation in vitro and in vivo and identified the microRNAs (miRNAs) associated with its antitumor effects...
April 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28440420/wound-healing-effect-of-an-astragalus%C3%A2-membranaceus-polysaccharide-and-its-mechanism
#8
Bingjiang Zhao, Xuanfen Zhang, Wei Han, Ju Cheng, Yonghong Qin
In the present study, a novel polysaccharide, APS2-1, was isolated and purified from Astragalus membranaceus using DEAE-cellulose and Sephadex G-100 chromatography. The effect of APS2‑1 on the promotion of wound healing was evaluated and its preliminary mechanism was investigated. In vitro experiments showed that APS2‑1 was able to promote human skin fibroblast (HSF) propagation and accelerate cell cycle progression. For further examination, a scalded mice model was used to verify the effect of APS2‑1 and investigate its mechanism of action...
April 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28439018/conservation-and-divergence-of-c-terminal-domain-structure-in-the-retinoblastoma-protein-family
#9
Tyler J Liban, Edgar M Medina, Sarvind Tripathi, Satyaki Sengupta, R William Henry, Nicolas E Buchler, Seth M Rubin
The retinoblastoma protein (Rb) and the homologous pocket proteins p107 and p130 negatively regulate cell proliferation by binding and inhibiting members of the E2F transcription factor family. The structural features that distinguish Rb from other pocket proteins have been unclear but are critical for understanding their functional diversity and determining why Rb has unique tumor suppressor activities. We describe here important differences in how the Rb and p107 C-terminal domains (CTDs) associate with the coiled-coil and marked-box domains (CMs) of E2Fs...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438385/small-molecules-inhibit-stat3-activation-autophagy-and-cancer-cell-anchorage-independent-growth
#10
Donghui Zhou, Maya Z Springer, David Xu, Degang Liu, Andy Hudmon, Kay F Macleod, Samy O Meroueh
Triple-negative breast cancers (TNBCs) lack the signature targets of other breast tumors, such as HER2, estrogen receptor, and progesterone receptor. These aggressive basal-like tumors are driven by a complex array of signaling pathways that are activated by multiple driver mutations. Here we report the discovery of 6 (KIN-281), a small molecule that inhibits multiple kinases including maternal leucine zipper kinase (MELK) and the non-receptor tyrosine kinase bone marrow X-linked (BMX) with single-digit micromolar IC50s...
March 23, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28438180/recent-advances-of-highly-selective-cdk4-6-inhibitors-in-breast-cancer
#11
REVIEW
Hanxiao Xu, Shengnan Yu, Qian Liu, Xun Yuan, Sridhar Mani, Richard G Pestell, Kongming Wu
Uncontrolled cell division is the hallmark of cancers. Full understanding of cell cycle regulation would contribute to promising cancer therapies. In particular, cyclin-dependent kinases 4/6 (CDK4/6), which are pivotal drivers of cell proliferation by combination with cyclin D, draw more and more attention. Subsequently, extensive studies were carried out to explore drugs inhibiting CDK4/6 and assess the efficacy and safety of these drugs in cancer, especially breast cancer. Due to the insuperable adverse events and the less activity observed in vivo, the drug development of the initial pan-CDK inhibitor flavopiridol was consequently discontinued, and then highly specific inhibitors were extensively researched and developed, including palbociclib (PD0332991), ribociclib (LEE011), and abemaciclib (LY2835219)...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28437471/mir-217-inhibits-triple-negative-breast-cancer-cell-growth-migration-and-invasion-through-targeting-klf5
#12
Wenhui Zhou, Fangfang Song, Qiuju Wu, Rong Liu, Lulu Wang, Cuicui Liu, You Peng, Shuqin Mao, Jing Feng, Ceshi Chen
Triple negative breast cancer (TNBC) is one of the most aggressive breast cancers without effective targeted therapies. Numerous studies have implied that KLF5 plays an important roles in TNBC. How is KLF5 regulated by microRNAs has not been well studied. Here, we demonstrated that miR-217 down-regulates the expression of KLF5 and KLF5's downstream target gene FGF-BP and Cyclin D1 in TNBC cell lines HCC1806 and HCC1937. Consequently, miR-217 suppresses TNBC cell growth, migration, and invasion. MiR-217 suppresses TNBC, at least partially, through down-regulating the KLF5 expression...
2017: PloS One
https://www.readbyqxmd.com/read/28436418/oxoaporphine-metal-complexes-co-ii-ni-ii-zn-ii-with-high-antitumor-activity-by-inducing-mitochondria-mediated-apoptosis-and-s-phase-arrest-in-hepg2
#13
Jiao-Lan Qin, Wen-Ying Shen, Zhen-Feng Chen, Li-Fang Zhao, Qi-Pin Qin, Yan-Cheng Yu, Hong Liang
Three new oxoaporphine Co(II), Ni(II) and Zn(II) complexes 1-3 have been synthesized and fully characterized. 1-3 have similar mononuclear structures with the metal and ligand ratio of 1:2. 1-3 exhibited higher cytotoxicity than the OD ligand and cisplatin against HepG2, T-24, BEL-7404, MGC80-3 and SK-OV-3/DDP cells, with IC50 value of 0.23-4.31 μM. Interestingly, 0.5 μM 1-3 significantly caused HepG2 arrest at S-phase, which was associated with the up-regulation of p53, p21, p27, Chk1 and Chk2 proteins, and decrease in cyclin A, CDK2, Cdc25A, PCNA proteins...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28435396/lentivirus-mediated-knockdown-of-p27rf-rho-inhibits-hepatocellular-carcinoma-cell-growth
#14
Shuli Xie, Guangyi Wang, Guofu Chen, Mingguang Zhu, Guoyue Lv
AIM OF THE STUDY: To investigate the effects of P27RF-Rho on hepatocellular carcinoma (HCC) cell growth and explore the possibility of using it as a novel therapeutic target for liver cancer treatment. MATERIAL AND METHODS: P27RF-Rho in HCC cells was silenced by lentivirus-mediated RNA interference, and the silencing effect was verified by RT-PCR. Cell proliferation was determined by MTT and clone formation assay. Cell cycle phase and apoptosis were detected through FACS...
2017: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/28435259/methotrexate-coupled-nanoparticles-and-magnetic-nanochemothermia-for-the-relapse-free-treatment-of-t24-bladder-tumors
#15
Marcus Stapf, Ulf Teichgräber, Ingrid Hilger
Heat-based approaches have been considered as promising tools due to their ability to directly eradicate tumor cells and/or increase the sensitivity of tumors to radiation- or chemotherapy. In particular, the heating of magnetic nanoparticles (MNPs) via an alternating magnetic field can provide a handy alternative for a localized tumor treatment. To amplify the efficacy of magnetically induced thermal treatments, we elucidated the superior tumor-destructive effect of methotrexate-coupled MNPs (MTX/MNPs) in combination with magnetic heating (nanochemothermia) over the thermal treatment alone...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28435223/efficacy-of-the-dual-pi3k-and-mtor-inhibitor-nvp-bez235-in-combination-with-imatinib-mesylate-against-chronic-myelogenous-leukemia-cell-lines
#16
Pengliang Xin, Chuntuan Li, Yan Zheng, Qunyi Peng, Huifang Xiao, Yuanling Huang, Xiongpeng Zhu
BACKGROUND: Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is a therapy target of cancer. We aimed to confirm the effect of dual PI3K/mTOR inhibitor NVP-BEZ235 on proliferation, apoptosis, and autophagy of chronic myelogenous leukemia (CML) cells and sensitivity of tyrosine kinase inhibitor in vitro. METHODS: Two human CML cell lines, K562 and KBM7R (T315I mutant strain), were used. The proliferation of CML cells was detected by MTS (Owen's reagent) assay...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28433657/mir-938-promotes-colorectal-cancer-cell-proliferation-via-targeting-tumor-suppressor-phlpp2
#17
Chang-Feng Li, Yong-Chao Li, Jing-Peng Jin, Zhen-Kun Yan, Dan-Dan Li
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Although the development of therapy approaches, the outcome of CRC patients still is poor, understanding the biological mechanism of CRC progression is critical to improve the treatment strategies. miRNAs regulate CRC progression, we found miR-938 was upregulated in CRC tissues and cells, MTT assay, colony formation assay and soft agar growth assay suggested miR-938 overexpression promoted CRC cell proliferation, miR-938 knockdown inhibited CRC cell proliferation...
April 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28433461/severely-impaired-adult-brain-neurogenesis-in-cyclin-d2-knock-out-mice-produces-very-limited-phenotypic-changes
#18
REVIEW
Robert K Filipkowski, Leszek Kaczmarek
The discovery of new neurons being produced in the brains of adult mammals (adult brain neurogenesis) began a quest to determine the function(s) of these cells. Major hypotheses in the field have assumed that these neurons play pivotal role, in particular, in learning and memory phenomena, mood control, and epileptogenesis. In our studies summarized herein, we used cyclin D2 knockout (KO) mice, as we have shown that cyclin D2 is the key factor in adult brain neurogenesis and thus its lack produces profound impairment of the process...
April 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28432293/quiescence-of-adult-oligodendrocyte-precursor-cells-requires%C3%A2-thyroid-hormone-and-hypoxia-to-activate-runx1
#19
Yasuhito Tokumoto, Shinpei Tamaki, Yasuaki Kabe, Keiyo Takubo, Makoto Suematsu
The adult mammalian central nervous system (CNS) contains a population of slowly dividing oligodendrocyte precursor cells (OPCs), i.e., adult OPCs, which supply new oligodendrocytes throughout the life of animal. While adult OPCs develop from rapidly dividing perinatal OPCs, the mechanisms underlying their quiescence remain unknown. Here, we show that perinatal rodent OPCs cultured with thyroid hormone (TH) under hypoxia become quiescent and acquire adult OPCs-like characteristics. The cyclin-dependent kinase inhibitor p15/INK4b plays crucial roles in the TH-dependent cell cycle deceleration in OPCs under hypoxia...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432176/a-phase-i-study-of-the-cdk4-6-inhibitor-ribociclib-lee011-in-pediatric-patients-with-malignant-rhabdoid-tumors-neuroblastoma-and-other-solid-tumors
#20
Birgit Geoerger, Franck Bourdeaut, Steven G DuBois, Matthias Fischer, James I Geller, Nicholas G Gottardo, Aurélien Marabelle, Andrew D J Pearson, Shakeel Modak, Thomas Cash, Giles W Robinson, Marlyane Motta, Alessandro Matano, Suraj G Bhansali, Jason R Dobson, Sudha Parasuraman, Susan N Chi
Purpose: The cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib (LEE011), displayed preclinical activity in neuroblastoma and malignant rhabdoid tumor (MRT) models. In this phase I study, the maximum tolerated dose (MTD) and recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of single-agent ribociclib were investigated in pediatric patients with neuroblastoma, MRT, or other cyclin D-CDK4/6-INK4-retinoblastoma pathway-altered tumors.Experimental Design: Patients (aged 1-21 years) received escalating once-daily oral doses of ribociclib (3-weeks-on/1-week-off)...
April 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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