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https://www.readbyqxmd.com/read/28431342/discovery-of-tetrahydrocarbazoles-as-dual-perk-and-prb-inhibitors
#1
Mahesh R Kulkarni, Madhav S Mane, Usha Ghosh, Rajiv Sharma, Nitin P Lad, Ankita Srivastava, Asha Kulkarni-Almeida, Prashant S Kharkar, Vijay M Khedkar, Shivaji S Pandit
The extracellular signal-regulated kinase (ERK) is one of the most important molecular targets for cancer that controls diverse cellular processes such as proliferation, survival, differentiation and motility. Similarly, the Rb (retinoblastoma protein) is a tumor suppressor protein and its function is to prevent excessive cell growth by inhibiting cell cycle progression. When the cell is ready to divide, pRb is phosphorylated, becomes inactive and allows cell cycle progression. Herein, we discovered a new series of tetrahydrocarbazoles as dual inhibitors of pERK and pRb phosphorylation...
March 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28420359/saikosaponins-induced-hepatotoxicity-in-mice-via-lipid-metabolism-dysregulation-and-oxidative-stress-a-proteomic-study
#2
Xiaoyu Li, Xiaojiaoyang Li, Junxian Lu, Youyi Huang, Lili Lv, Yongfu Luan, Runping Liu, Rong Sun
BACKGROUND: Radix Bupleuri (RB) has been popularly used for treating many liver diseases such as chronic hepatic inflammation and viral Hepatitis in China. Increasing clinical and experimental evidence indicates the potential hepatotoxicity of RB or prescriptions containing RB. Recently, Saikosaponins (SS) have been identified as major bioactive compounds isolated from RB, which may be also responsible for RB-induced liver injury. METHODS: Serum AST, ALT and LDH levels were determined to evaluate SS-induced liver injury in mice...
April 19, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28418919/znf452-facilitates-tumor-proliferation-and-invasion-via-activating-akt-gsk3%C3%AE-signaling-pathway-and-predicts-poor-prognosis-of-non-small-cell-lung-cancer-patients
#3
Xiupeng Zhang, Haijing Zhou, Yong Zhang, Lin Cai, Guiyang Jiang, Ailin Li, Yuan Miao, Qingchang Li, Xueshan Qiu, Enhua Wang
ZNF452 is a zinc-finger protein family member which contains an isolated SCAN (SRE-ZBP, CTfin51, AW-1 and Number 18 cDNA) zinc-finger domain. Despite the SCAN N-terminus domain is known to play a role in transcriptional regulation of genes involved in cell survival and differentiation, there are no precise cellular functions that have been assigned to ZNF452. In the present study, we found that either endogenous or exogenous ZNF452 was overexpressed in the cytoplasm of NSCLC cells and positive ratio of ZNF452 in NSCLC samples (50...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404959/inhibition-of-the-prolyl-isomerase-pin1-enhances-the-ability-of-sorafenib-to-induce-cell-death-and-inhibit-tumor-growth-in-hepatocellular-carcinoma
#4
Min Zheng, Huijuan Xu, Xin-Hua Liao, Champ Peng Chen, Arina Li Zhang, Wenxian Lu, Long Wang, Dayun Yang, Jichuang Wang, Hekun Liu, Xiao Zhen Zhou, Kun Ping Lu
Hepatocellular carcinoma (HCC) is the sixth most common cancer, but is the second leading cause of cancer deaths, partially due to its heterogeneity and drug resistance. Sorafenib is the only medical treatment with a proven efficacy against advanced HCC, but its overall clinical efficacy is still modest. Therefore, a major challenge is how to improve its therapeutic efficacy. The unique prolyl isomerase Pin1 regulates numerous cancer-driving pathways. Notably, Pin1 is overexpressed in about 70% HBV-positive HCC patients and contributes to HCC tumorigenesis...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402854/in%C3%A2-vivo-interplay-between-p27-kip1-gata3-atoh1-and-pou4f3-converts-non-sensory-cells-to-hair-cells-in-adult-mice
#5
Bradley J Walters, Emily Coak, Jennifer Dearman, Grace Bailey, Tetsuji Yamashita, Bryan Kuo, Jian Zuo
Hearing loss is widespread and persistent because mature mammalian auditory hair cells (HCs) are nonregenerative. In mice, the ability to regenerate HCs from surrounding supporting cells (SCs) declines abruptly after postnatal maturation. We find that combining p27(Kip1) deletion with ectopic ATOH1 expression surmounts this age-related decline, leading to conversion of SCs to HCs in mature mouse cochleae and after noise damage. p27(Kip1) deletion, independent of canonical effects on Rb-family proteins, upregulated GATA3, a co-factor for ATOH1 that is lost from SCs with age...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28398584/genomic-profiles-of-low-grade-murine-gliomas-evolve-during-progression-to-glioblastoma
#6
Mark Vitucci, David M Irvin, Robert S McNeill, Ralf S Schmid, Jeremy M Simon, Harshil D Dhruv, Marni B Siegel, Andrea M Werneke, Ryan E Bash, Seungchan Kim, Michael E Berens, C Ryan Miller
Background: Gliomas are diverse neoplasms with multiple molecular subtypes. How tumor-initiating mutations relate to molecular subtypes as these tumors evolve during malignant progression remains unclear. Methods: We used genetically engineered mouse models, histopathology, genetic lineage tracing, expression profiling, and copy number analyses to examine how genomic tumor diversity evolves during the course of malignant progression from low- to high-grade disease...
April 7, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28388564/antiproliferative-effect-of-zstk474-alone-or-in-combination-with-chemotherapeutic-drugs-on-hl60-and-hl60-adr-cells
#7
Qianxiang Zhou, Yali Chen, Lei Zhang, Yuxu Zhong, Zhe Zhang, Ran Wang, Meihua Jin, Min Gong, Yuling Qiu, Dexin Kong
While chemotherapy remains to be one of the main approaches in the clinical treatment of acute myeloid leukemia (AML), multidrug resistance (MDR) has become a serious problem which limits the therapeutic efficacy. The important roles of the PI3K/Akt pathway in modulating cell proliferation and MDR suggest that PI3K inhibitor might be effective for treatment of AML. In the present study, the antiproliferative effects of PI3K inhibitor ZSTK474 on AML cell HL60 and the adriamycin (ADR)-resistant HL60/ADR cells were investigated...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28387346/plk1-regulates-the-repressor-function-of-foxm1b-by-inhibiting-its-interaction-with-the-retinoblastoma-protein
#8
Nishit K Mukhopadhyay, Vaibhav Chand, Akshay Pandey, Dragana Kopanja, Janai R Carr, Yi-Ju Chen, Xiubei Liao, Pradip Raychaudhuri
FoxM1b is a cell cycle-regulated transcription factor, whose over-expression is a marker for poor outcome in cancers. Its transcriptional activation function requires phosphorylation by Cdk1 or Cdk2 that primes FoxM1b for phosphorylation by Plk1, which triggers association with the co-activator CBP. FoxM1b also possesses transcriptional repression function. It represses the mammary differentiation gene GATA3 involving DNMT3b and Rb. We investigated what determines the two distinct functions of FoxM1b: activation and repression...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28379093/single-amino-acid-substitution-in-lc-cdr1-induces-russell-body-phenotype-that-attenuates-cellular-protein-synthesis-through-eif2%C3%AE-phosphorylation-and-thereby-downregulates-igg-secretion-despite-operational-secretory-pathway-traffic
#9
Haruki Hasegawa, Ann Hsu, Christine E Tinberg, Karen E Siegler, Aaron A Nazarian, Mei-Mei Tsai
Amino acid sequence differences in the variable region of immunoglobulin (Ig) cause wide variations in secretion outputs. To address how a primary sequence difference comes to modulate immunoglobulin (Ig) secretion, we investigated the biosynthetic process of two human IgG2κ monoclonal antibodies (mAbs) that differ only by one amino acid in the light chain complementarity-determining region 1 whilst showing ∼20-fold variance in secretion titer. Although poorly secreted, the lower-secreting mAb of the two was by no means defective in terms of its folding stability, antigen binding, and in vitro biologic activity...
April 5, 2017: MAbs
https://www.readbyqxmd.com/read/28377200/molecular-cloning-characterization-and-function-of-a-germinal-center-kinase-mst4-gene-from-litopenaeus-vannamei-in-response-to-vibrio-alginolyticus-challenge-in-tlr-traf6-signaling-pathway
#10
Chang-Sheng Zhao, Di Huang, Ting Peng, Ming-Zhu Huang, Chen-Ying Xie, Jun Chen, Jing-Rong Kong, Ren-Chong Xie, Yuan Liu, Wei-Na Wang
The serine/threonine protein kinase MST4 plays multiple roles in the regulation of signaling pathways that govern cellular processes including mitosis, migration, homeostasis, polarity, proliferation, differentiation and apoptosis. Here we report the identification and characterization of the full-length sequence of LvMST4 from the shrimp L. vannamei, and investigations into its role in the shrimp's immune response to infection by the pathogenic bacterium Vibrio alginolyticus. Subcellular localization assays demonstrated the enzyme's presence in the shrimp's cytoplasm, and tissue-specific expression analysis revealed that it is expressed ubiquitously but at different levels in different tissues...
April 6, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28371875/plasmacytoid-urothelial-carcinoma-of-the-urinary-bladder-a-clinicopathologic-and-immunohistochemical-analysis-of-49-cases
#11
Melanie D Fox, Li Xiao, Miao Zhang, Ashish M Kamat, Arlene Siefker-Radtke, Li Zhang, Colin P Dinney, Bogdan Czerniak, Charles C Guo
Objectives: Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare histologic variant. We retrospectively analyzed a large series of bladder PUC from a single institution. Methods: The patients consisted of 44 men and five women with a mean age of 62 years (range, 45-86 years). Results: PUC was pure in 23 cases and mixed with other histologic types in 26 cases. All PUCs diffusely invaded the bladder wall. Most PUCs lacked immunoreactivity for the retinoblastoma (RB) gene protein (12/32) and E-cadherin (8/30)...
March 23, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28368741/molecular-targeting-of-vegf-vegfr-signaling-by-the-anti-vegf-monoclonal-antibody-bd0801-inhibits-the-growth-and-induces-apoptosis-of-human-hepatocellular-carcinoma-cells-in-vitro-and-in-vivo
#12
Lin Liu, Shukui Qin, Yinghui Zheng, Li Han, Minmin Zhang, Nuo Luo, Zhengcao Liu, Ning Gu, Xiaoyi Gu, Xiaojin Yin
Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related deaths with 750,000 newly diagnosed cases each year. Surgery, radiotherapy, and chemotherapy constitute the main treatment modalities for HCC, but liver cirrhosis and damage often occur. Molecular targeted drugs have been recently developed to treat HCC. Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) autocrine signaling is closely related to the growth, progression, and metastasis of HCC, making the VEGF/VEGFR axis an ideal target for the development of molecular targeted agents...
March 4, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28368473/targeting-myc-as-a-therapeutic-intervention-for-anaplastic-thyroid-cancer
#13
Keisuke Enomoto, Xuguang Zhu, Sunmi Park, Li Zhao, Yuelin J Zhu, Mark C Willingham, Jun Qi, John A Copland, Paul Meltzer, Sheue-Yann Cheng
Context: Recent studies showed that transcription of the MYC gene is driven by interaction of bromodomain and extraterminal domain (BET) proteins with acetylated histones on chromatin. A potent inhibitor, JQ1, which effectively disrupts the interaction of BET proteins with acetylated histones, preferentially suppresses transcription of the MYC gene. We recently reported that JQ1 decreased thyroid tumor growth and improved survival in a mouse model of anaplastic thyroid cancer (ATC) by targeting MYC transcription...
March 28, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28368424/p53-rb-inhibition-induces-metastatic-adrenocortical-carcinomas-in-a-preclinical-transgenic-model
#14
M Batisse-Lignier, I Sahut-Barnola, F Tissier, T Dumontet, M Mathieu, C Drelon, J-C Pointud, C Damon-Soubeyrand, G Marceau, J-L Kemeny, J Bertherat, I Tauveron, P Val, A Martinez, A-M Lefrançois-Martinez
Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Pan-genomic analyses identified p53/Rb and WNT/β-catenin signaling pathways as main contributors to the disease. However, isolated β-catenin constitutive activation failed to induce malignant progression in mouse adrenocortical tumors. Therefore, there still was a need for a relevant animal model to study ACC pathogenesis and to test new therapeutic approaches. Here, we have developed a transgenic mice model with adrenocortical specific expression of SV40 large T-antigen (AdTAg mice), to test the oncogenic potential of p53/Rb inhibition in the adrenal gland...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28361860/do-mrps18-2-and-rb-proteins-cooperate-to-control-cell-stemness-and-differentiation-preventing-cancer-development
#15
E Kashuba, M Mushtaq
In childhood tumors, including retinoblastoma, osteosarcoma, and neuroblastoma, the RB-E2F1 pathway is inactivated, as a rule. These tumors arise from precursor cells that fail to undergo the terminal differentiation. Noteworthy, the RB1-encoded protein (RB) does not control the cell cycle in embryonic stem cells. It has not been yet well understood how RB controls cell stemness and differentiation. The question arises why "inactive" RB is required for the survival and stemness of cells? Recently, we have found that overexpression of the RB-binding protein MRPS18-2 (S18-2) in primary fibroblasts leads to their immortalization, which is accompanied by the induction of embryonic stem cell markers and, eventually, malignant transformation...
March 2017: Experimental Oncology
https://www.readbyqxmd.com/read/28357524/molecular-connections-of-obesity-and-aging-a-focus-on-adipose-protein-53-and-retinoblastoma-protein
#16
REVIEW
Dinh-Toi Chu, Yang Tao
Obesity is an induced health problem that human beings have been facing with non-optimal treatment so far. Humans are on average getting fatter with age, and obesity and aging interact each other to shorten lifetime and decrease life quality. Obesity also causes several aging related-disorders such as cancer, strokes, cardiovascular disease, high blood pressure and type 2 diabetes. So, the molecular connections between aging and obesity are promising targets for bio-medical researches and innovative therapies of many health problems...
March 30, 2017: Biogerontology
https://www.readbyqxmd.com/read/28357396/chlamydia-trachomatis-struggle-to-keep-its-host-alive
#17
COMMENT
Barbara S Sixt, Raphael H Valdivia, Guido Kroemer
Bacteria of the phylum Chlamydiae infect a diverse range of eukaryotic host species, including vertebrate animals, invertebrates, and even protozoa. Characteristics shared by all Chlamydiae include their obligate intracellular lifestyle and a biphasic developmental cycle. The infectious form, the elementary body (EB), invades a host cell and differentiates into the replicative form, the reticulate body (RB), which proliferates within a membrane-bound compartment, the inclusion. After several rounds of division, RBs retro-differentiate into EBs that are then released to infect neighboring cells...
March 2, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28350531/phytophthora-infestans-effectors-ipi-o1-and-ipi-o4-each-contribute-to-pathogen-virulence
#18
Yu Chen, Dennis A Halterman
Potato late blight, caused by the oomycete pathogen Phytophthora infestans, is one of the most destructive plant diseases. Despite decades of intensive breeding efforts, it remains a threat to potato production worldwide, because newly evolved pathogen strains have overcome major resistance genes quickly. The RB protein, from the diploid wild potato species Solanum bulbocastanum, confers partial resistance to most P. infestans strains through its recognition of members of the corresponding pathogen effector protein family IPI-O...
May 2017: Phytopathology
https://www.readbyqxmd.com/read/28348560/specific-strains-of-lactic-acid-bacteria-differentially-modulate-the-profile-of-adipokines-in-vitro
#19
Emanuel Fabersani, María Claudia Abeijon-Mukdsi, Romina Ross, Roxana Medina, Silvia González, Paola Gauffin-Cano
Obesity induces local/systemic inflammation accompanied by increases in macrophage infiltration into adipose tissue and production of inflammatory cytokines, chemokines, and hormones. Previous studies have shown that probiotics could improve the intestinal dysbiosis induced by metabolic diseases such as obesity, diabetes, and metabolic syndrome. Microorganisms could (directly or indirectly) affect adipokine levels due to their capacity to induce translocation of several intestinal microbial antigens into systemic circulation, which could lead to metabolic endotoxemia or produce immunomodulation in different organs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28335821/differential-gene-expression-profiling-of-endometrium-during-the-mid-luteal-phase-of-the-estrous-cycle-between-a-repeat-breeder-rb-and-non-rb-cows
#20
Ken-Go Hayashi, Misa Hosoe, Keiichiro Kizaki, Shiori Fujii, Hiroko Kanahara, Toru Takahashi, Ryosuke Sakumoto
BACKGROUND: Repeat breeding directly affects reproductive efficiency in cattle due to an increase in services per conception and calving interval. This study aimed to investigate whether changes in endometrial gene expression profile are involved in repeat breeding in cows. Differential gene expression profiles of the endometrium were investigated during the mid-luteal phase of the estrous cycle between repeat breeder (RB) and non-RB cows using microarray analysis. METHODS: The caruncular (CAR) and intercaruncular (ICAR) endometrium of both ipsilateral and contralateral uterine horns to the corpus luteum were collected from RB (inseminated at least three times but not pregnant) and non-RB cows on Day 15 of the estrous cycle (4 cows/group)...
March 23, 2017: Reproductive Biology and Endocrinology: RB&E
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