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https://www.readbyqxmd.com/read/29767411/mek1-2-inhibition-by-binimetinib-is-effective-as-a-single-agent-and-potentiates-the-actions-of-venetoclax-and-abt-737-under-conditions-that-mimic-the-chronic-lymphocytic-leukaemia-cll-tumour-microenvironment
#1
Kyle Crassini, Yandong Shen, William S Stevenson, Richard Christopherson, Chris Ward, Stephen P Mulligan, O Giles Best
The survival and proliferation of chronic lymphocytic leukaemia (CLL) cells is driven by multiple signalling pathways, including those mediated by the B cell, Toll-like and chemokine receptors. Many of these pathways converge on the same signalling molecules, including those involved in the Raf-1/MEK/Erk1/2-MAPK pathway. We investigated the effects of the MEK1/2 (also termed MAP2K1/2) inhibitor, binimetinib, against CLL cells cultured under conditions that mimic aspects of the tumour microenvironment. Binimetinib blocked CLL cell survival induced by stroma-conditioned media and phorbol myristylate (PMA)...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29763892/interleukin-33-predicts-poor-prognosis-and-promotes-renal-cell-carcinoma-cell-growth-through-its-receptor-st2-and-the-jnk-signaling-pathway
#2
Chang-Wen Wu, Yi-Guo Wu, Cheng Cheng, Zheng-Dong Hong, Zi-Min Shi, Shuang-Quan Lin, Jie Li, Xiao-Yi He, An-Yi Zhu
BACKGROUND/AIMS: Renal cell carcinoma (RCC) is currently the ninth most common cancer in men. Interleukin (IL)-33 expression has previously been associated with a number of cancers; however, its biological role in RCC is poorly understood. In this study, we sought to elucidate the role of IL-33 in RCC. METHODS: Serum IL-33 levels were measured by ELISA. IL-33 expression in clinical RCC samples was examined by immunocytochemistry. The proliferation and apoptosis rate of RCC were determined by CCK8 and flow cytometry...
May 10, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29748555/ptbp1-enhances-mir-101-guided-ago2-targeting-to-mcl1-and-promotes-mir-101-induced-apoptosis
#3
Jia Cui, William J Placzek
Myeloid cell leukemia 1 (MCL1) is a key anti-apoptotic protein belonging to the BCL-2 protein family. To preserve normal cellular homeostasis, cells must maintain strict control over MCL1 expression. Overexpression of MCL1 has been identified as a key contributor to tumorigenesis, and further enables resistance to a number of anti-cancer chemotherapies. Thus, there is an ongoing interest to develop selective MCL1 inhibitors. In order to better target MCL1, it is essential to understand the molecular mechanisms that regulate MCL1 expression in cells...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29745292/unraveling-the-molecular-mechanism-of-benzothiophene-and-benzofuran-scaffold-merged-compounds-binding-to-anti-apoptotic-myeloid-cell-leukemia-1
#4
Parthiban Marimuthu, Kalaimathy Singaravelu
Myeloid cell leukemia 1 (Mcl1), is an anti-apoptotic member of the Bcl-2 family proteins, has gained considerable importance due to its overexpression activity prevents the oncogenic cells to undergo apoptosis. This overexpression activity of Mcl1 eventually develops strong resistance to a wide variety of anticancer agents. Therefore, designing novel inhibitors with potentials to elicit higher binding affinity and specificity to inhibit Mcl1 activity is of greater importance. Thus, Mcl1 acts as an attractive cancer target...
May 10, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29739970/identifying-microrna-determinants-of-human-myelopoiesis
#5
Megha Rajasekhar, Ulf Schmitz, Stephane Flamant, Justin J-L Wong, Charles G Bailey, William Ritchie, Jeff Holst, John E J Rasko
Myelopoiesis involves differentiation of hematopoietic stem cells to cellular populations that are restricted in their self-renewal capacity, beginning with the common myeloid progenitor (CMP) and leading to mature cells including monocytes and granulocytes. This complex process is regulated by various extracellular and intracellular signals including microRNAs (miRNAs). We characterised the miRNA profile of human CD34+ CD38+ myeloid progenitor cells, and mature monocytes and granulocytes isolated from cord blood using TaqMan Low Density Arrays...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29734217/dysregulation-of-apoptosis-and-autophagy-gene-expression-in-pbmcs-of-efficiently-treated-hiv-infected-patients
#6
Amandine Serrano, Saïd El Haddad, Frédéric Moal, Thierry Prazuck, Eric Legac, Chloé Robin, Fabienne Brule, Stéphane Charpentier, Thierry Normand, Alain Legrand, Laurent Hocqueloux, Lucile Mollet
OBJECTIVE: We measure the transcript levels of the pro-apoptotic GALIG, anti-apoptotic MCL1 genes and those of the autophagy genes BECN1, MAP1LC3B, ATG9a, P62/SQSTM1, GABARAP, GABARAPL1 and GABARAPL2 to define if mRNA alteration can characterize HIV infected patients effectively treated with combined antiretroviral therapy (cART). DESIGN: Monocentric pilot study conducted on PBMC of 40 uninfected donors and 27 HIV positive patients effectively treated by cART for at least 8...
May 3, 2018: AIDS
https://www.readbyqxmd.com/read/29733883/distinct-apoptotic-blocks-mediate-resistance-to-panher-inhibitors-in-her2-breast-cancer-cells
#7
Bahriye Karakas, Yeliz Ozmay, Huveyda Basaga, Ozgur Gul, Ozgur Kutuk
Despite the development of novel targeted therapies, de novo or acquired chemoresistance remains a significant factor for treatment failure in breast cancer therapeutics. Neratinib and dacomitinib are irreversible panHER inhibitors, which block their autophosphorylation and downstream signaling. Moreover, neratinib and dacomitinib have been shown to activate cell death in HER2-overexpressing cell lines. Here we showed that increased MCL1 and decreased BIM and PUMA mediated resistance to neratinib in ZR-75-30 and SKBR3 cells while increased BCL-XL and BCL-2 and decreased BIM and PUMA promoted neratinib resistance in BT474 cells...
May 4, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29719405/microrna-26a-induces-a-mitochondrial-apoptosis-mediated-by-p53-through-targeting-to-inhibit-mcl1-in-human-hepatocellular-carcinoma
#8
Xiao-Mei Gao, Ying Zhu, Jian-Hua Li, Xiang-Yu Wang, Xiao-Fei Zhang, Chen-He Yi, Xin Yang
Aim: We have previously found that microRNA-26a (miR-26a) is a potential tumor suppressor in hepatocellular carcinoma (HCC). In this study, we further explored the roles of miR-26a in HCC apoptosis. Methods: miR-26a expression levels were detected in HCC tissues by real-time PCR. Statistical analysis was performed to explore the correlation between miR-26a expression and apoptotic cells and the antiapoptotic protein levels. In vitro assays were performed to investigate the roles of miR-26a in HCC apoptosis...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29696703/mcl1-gene-co-expression-module-stratifies-multiple-myeloma-and-predicts-response-to-proteasome-inhibitor-based-therapy
#9
Ayaz Ali Samo, Jiuyi Li, Min Zhou, Yingyu Sun, Yang Yuan, Yunqiu Zhang, Li Jing, Mark van Duin, Xuzhang Lu, Xiaolong Fan
Multiple myeloma (MM) is the second most common hematologic cancer, characterized by abnormal accumulation of plasma cells in the bone marrow. The extensive biological and clinical heterogeneity of MM hinders effective treatment and etiology research. Several molecular classification systems of prognostic impact have been proposed, but they do not predict the response to treatment nor do they correlate to plasma cell development pathways. Here we describe the classification of MM into two distinct subtypes based on the expression levels of a gene module co-expressed with MCL1 (MCL1-M), a regulator of plasma cell survival...
April 26, 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29675777/inhibition-of-p16-ink4a-to-rejuvenate-aging-human-cardiac-progenitor-cells-via-the-upregulation-of-anti-oxidant-and-nf%C3%AE%C2%BAb-signal-pathways
#10
Roshni V Khatiwala, Shuning Zhang, Xiuchun Li, Neil Devejian, Edward Bennett, Chuanxi Cai
Autologous human cardiac stem/progenitor cell (hCPC) therapy is a promising treatment that has come into use in recent years for patients with cardiomyopathy. Though innovative in theory, a major hindrance to the practical application of this treatment is that the hCPCs of elderly patients, who are most susceptible to myocardial disease, are senescent and prone to cell death. Rejuvenating hCPCs from elderly patients may help overcome this obstacle, and can be accomplished by reversing entry into the cellular stage of senescence...
April 19, 2018: Stem Cell Reviews
https://www.readbyqxmd.com/read/29661725/importin-%C3%AE-and-exportin-5-are-indicators-of-acute-viral-infection-correlation-of-their-detection-with-commercially-available-detection-kits
#11
Gerard J Nuovo, Cecilia Vianna de Andrade, Chandini Thirukkumaran, Alcina F Nicol
This work focused on immunohistochemistry markers of acute viral infections. Viral infected cells were detected by in situ based methods (reovirus, rabies virus) or cytologic changes (human papillomavirus, molloscum contagiosum virus, herpes simplex virus). Two proteins involved in nuclear trafficking, importin-β and exportin-5, were detected in the infected cells for each virus and not in the control tissues. A wide variety of other proteins, including caspase-3, and bcl-2 family members (bcl2, bclX, MCL1, BAK, BAX, BIM, BAD) showed wide variations in expression among the different viral infections...
January 10, 2018: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29593724/mirnome-expression-analysis-reveals-new-players-on-leprosy-immune-physiopathology
#12
Claudio Guedes Salgado, Pablo Pinto, Raquel Carvalho Bouth, Angélica Rita Gobbo, Ana Caroline Cunha Messias, Tatiana Vinasco Sandoval, André Mauricio Ribeiro Dos Santos, Fabiano Cordeiro Moreira, Amanda Ferreira Vidal, Luiz Ricardo Goulart, Josafá Gonçalves Barreto, Moisés Batista da Silva, Marco Andrey Cipriani Frade, John Stewart Spencer, Sidney Santos, Ândrea Ribeiro-Dos-Santos
Leprosy remains as a public health problem and its physiopathology is still not fully understood. MicroRNAs (miRNA) are small RNA non-coding that can interfere with mRNA to regulate gene expression. A few studies using DNA chip microarrays have explored the expression of miRNA in leprosy patients using a predetermined set of genes as targets, providing interesting findings regarding the regulation of immune genes. However, using a predetermined set of genes restricted the possibility of finding new miRNAs that might be involved in different mechanisms of disease...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29568373/increased-expression-of-mnk1b-the-spliced-isoform-of-mnk1-predicts-poor-prognosis-and-is-associated-with-triple-negative-breast-cancer
#13
Celia Pinto-Díez, Eva M García-Recio, M Isabel Pérez-Morgado, Marta García-Hernández, Lara Sanz-Criado, Silvia Sacristán, M Val Toledo-Lobo, Belén Pérez-Mies, Isabel Esteban-Rodríguez, Alejandro Pascual, Mercedes Garcia-Villanueva, Noelia Martínez-Jañez, Víctor M González, M Elena Martín
MAP kinase interacting kinases (MNKs) modulate the function of oncogene eukaryotic initiation factor 4E (eIF4E) through phosphorylation, which is necessary for oncogenic transformation. MNK1 gives rise to two mRNAs and thus two MNK1 isoforms, named MNK1a and MNK1b. MNK1b, the splice variant of human MNK1a, is constitutively active and independent of upstream MAP kinases. In this study, we have analyzed the expression of both MNK1 isoforms in 69 breast tumor samples and its association with clinicopathologic/prognostic characteristics of breast cancer...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29567880/myeloid-cell-leukemia-1-protein-expression-and-myeloid-cell-leukemia-1-gene-amplification-in-non-small-cell-lung-cancer
#14
Tony El Jabbour, Siddhartha Dilip Dalvi, Sungeun Kim, Christine Sheehan, Jeffrey S Ross
Background: Myeloid cell leukemia-1 (Mcl-1) is a member of the B-cell lymphoma 2 family known to play a significant role in the regulation of apoptosis. Mcl-1 expression has been studied in nonsmall cell lung cancer (NSCLC) cell lines but has not been previously evaluated as a prognostic factor in clinical samples. Materials and Methods: Formalin-fixed, paraffin-embedded sections from 119 NSCLC, including 33 squamous cell carcinomas (SCC), 55 adenocarcinomas (AC), and 31 either pure adenocarcinoma in situ (AIS) or AC with lepidic features were immunostained by an automated method with rabbit polyclonal Mcl-1...
January 2018: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/29554896/extract-of-stellerachamaejasme-l-esc-inhibits-growth-and-metastasis-of-human-hepatocellular-carcinoma-via-regulating-microrna-expression
#15
Xiaoni Liu, Shuang Wang, Jianji Xu, Buxin Kou, Dexi Chen, Yajie Wang, Xiaoxin Zhu
BACKGROUND: MicroRNAs(miRNAs)are involved in the initiation and progression of hepatocellular carcinoma. ESC, an extract of Stellerachamaejasme L, had been confirmed as a potential anti-tumor extract of Traditional Chinese Medicine. In light of the important role of miRNAs in hepatocellular carcinoma, we questioned whether the inhibitory effects of ESC on hepatocellular carcinoma (HCC) were associated with miRNAs. METHODS: The proliferation inhibition of ESC on HCC cells was measured with MTT assay...
March 20, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29552199/sorafenib-inhibited-cell-growth-through-the-mek-erk-signaling-pathway-in-acute-promyelocytic-leukemia-cells
#16
Yunjie Zhang, Gangcan Li, Xin Liu, Yanping Song, Jia Xie, Guang Li, Jingjing Ren, Hao Wang, Jiao Mou, Jinqian Dai, Feng Liu, Liang Guo
The present study assessed the mechanism underlying the effect of sorafenib on the proliferation and apoptosis of the acute promyelocytic leukemia (APL) cell line NB4. NB4 cells were treated with different concentrations of sorafenib (0, 1.5, 3, 6, and 12 µM) for 24, 48 and 72 h. Cell proliferation, cell cycle, and apoptosis were analyzed using an MTT assay and flow cytometry analysis, respectively. Reverse transcription-semi-quantitative polymerase chain reaction and western blot analysis were performed to assess the expression of caspase-3, caspase-8, myeloid cell leukemia (MCL)1, cyclin D1, mitogen-activated protein kinase (MEK), phosphorylated (P)-MEK, extracellular signal-regulated kinase (ERK) and P-ERK...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29545333/a-mir-29b-byproduct-sequence-exhibits-potent-tumor-suppressive-activities-via-inhibition-of-nf-%C3%AE%C2%BAb-signaling-in-kras-mutant-colon-cancer-cells
#17
Akira Inoue, Tsunekazu Mizushima, Xin Wu, Daisuke Okuzaki, Nanami Kambara, Sho Ishikawa, Jiaqi Wang, Yamin Qian, Haruka Hirose, Yuhki Yokoyama, Ryo Ikeshima, Masayuki Hiraki, Norikatsu Miyoshi, Hidekazu Takahashi, Naotsugu Haraguchi, Taishi Hata, Chu Matsuda, Yuichiro Doki, Masaki Mori, Hirofumi Yamamoto
We previously demonstrated that miR-29b-3p is a hopeful miRNA-based therapy against colorectal cancer. In this study, we aimed to clarify a value of miR-29b-1-5p as a next-generation treatment, especially for KRAS -mutant colorectal cancer. RT-PCR assay showed that the expression of miR-29b-3p was high, and its partner strand, miR-29b-1-5p, level was only negligible in clinical colorectal cancer samples. Mimic-miR-29b-1-5p significantly inhibited proliferation of KRAS -mutant colorectal cancer cell lines DLD1 and SW480 and KRAS wild-type HT29 cells...
May 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29523777/intracellular-desmoglein-2-cleavage-sensitizes-epithelial-cells-to-apoptosis-in-response-to-pro-inflammatory-cytokines
#18
Mark Yulis, Miguel Quiros, Roland Hilgarth, Charles A Parkos, Asma Nusrat
Desmosomal cadherins mediate intercellular adhesion and have also been shown to regulate homeostatic signaling in epithelial cells. We have previously reported that select pro-inflammatory cytokines induce Dsg2 ectodomain cleavage and shedding from intestinal epithelial cells (IECs). Dsg2 extracellular cleaved fragments (Dsg2 ECF) function to induce paracrine pro-proliferative signaling in epithelial cells. In this study, we show that exposure of IECs to pro-inflammatory cytokines interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) resulted in Dsg2 intracellular cleavage and generation of a ~55 kDa fragment (Dsg2 ICF)...
March 9, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29484526/mir-146a-down-regulation-alleviates-h-2-o-2-induced-cytotoxicity-of-pc12-cells-by-regulating-mcl1-jak-stat-pathway-mir-146a-down-regulation-relieves-h2o2-induced-pc12-cells-cytotoxicity-by-mcl1-jak-stat
#19
Xuecheng Yang, Xin Mao, Xuemei Ding, Fengju Guan, Yuefeng Jia, Lei Luo, Bin Li, Hailin Tan, Caixia Cao
Oxidative stress and miRNAs have been confirmed to play an important role in neurological diseases. The study aimed to explore the underlying effect and mechanisms of miR-146a in H2 O2 -induced injury of PC12 cells. Here, PC12 cells were stimulated with 200 μM of H2 O2 to construct oxidative injury model. Cell injury was evaluated on the basis of the changes in cell viability, migration, invasion, apoptosis, and DNA damage. Results revealed that miR-146a expression was up-regulated in H2 O2 -induced PC12 cells...
February 26, 2018: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/29484127/malat1-mir-101-3p-mcl1-axis-mediates-cisplatin-resistance-in-lung-cancer
#20
Huaqi Wang, Li Wang, Guojun Zhang, Chunya Lu, Heying Chu, Rui Yang, Guoqiang Zhao
In this study, we investigated the mechanism by which lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) mediates cisplatin resistance in lung cancer. Lung cancer patients with high MALAT1 levels were associated with cisplatin resistance and low overall survival. Moreover, cisplatin-resistant A549/DDP cells showed higher MALAT1 expression than cisplatin-sensitive lung cancer cells (A549, H460, H1299 and SPC-A1). Dual luciferase reporter and RNA immunoprecipitation assays showed direct binding of miR-101-3p to MALAT1...
January 26, 2018: Oncotarget
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