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https://www.readbyqxmd.com/read/28931068/erk1-2-signalling-protects-against-apoptosis-following-endoplasmic-reticulum-stress-but-cannot-provide-long-term-protection-against-bax-bak-independent-cell-death
#1
Nicola J Darling, Kathryn Balmanno, Simon J Cook
Disruption of protein folding in the endoplasmic reticulum (ER) causes ER stress. Activation of the unfolded protein response (UPR) acts to restore protein homeostasis or, if ER stress is severe or persistent, drive apoptosis, which is thought to proceed through the cell intrinsic, mitochondrial pathway. Indeed, cells that lack the key executioner proteins BAX and BAK are protected from ER stress-induced apoptosis. Here we show that chronic ER stress causes the progressive inhibition of the extracellular signal-regulated kinase (ERK1/2) signalling pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28915653/dual-targeting-of-mdm2-and-bcl2-as-a-therapeutic-strategy-in-neuroblastoma
#2
Alan Van Goethem, Nurten Yigit, Myrthala Moreno-Smith, Sanjeev A Vasudevan, Eveline Barbieri, Frank Speleman, Jason Shohet, Jo Vandesompele, Tom Van Maerken
Wild-type p53 tumor suppressor activity in neuroblastoma tumors is hampered by increased MDM2 activity, making selective MDM2 antagonists an attractive therapeutic strategy for this childhood malignancy. Since monotherapy in cancer is generally not providing long-lasting clinical responses, we here aimed to identify small molecule drugs that synergize with idasanutlin (RG7388). To this purpose we evaluated 15 targeted drugs in combination with idasanutlin in three p53 wild type neuroblastoma cell lines and identified the BCL2 inhibitor venetoclax (ABT-199) as a promising interaction partner...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901451/genomic-profile-of-oral-squamous-cell-carcinomas-with-an-adjacent-leukoplakia-or-with-an-erythroleukoplakia-that-evolved-after-the-treatment-of-primary-tumor-a-report-of-two-cases
#3
Ilda P Ribeiro, Francisco Marques, Leonor Barroso, Joana Rodrigues, Francisco Caramelo, Joana B Melo, Isabel M Carreira
Oral leukoplakia and erythroleukoplakia are common oral potentially malignant disorders diagnosed in the oral cavity. The specific outcome of these lesions remains to be elucidated, as their malignant transformation rate exhibits great variation. The ability to predict which of those potentially malignant lesions are likely to progress to cancer would be vital to guide their future clinical management. The present study reported two patients with tongue squamous cell carcinoma: Case study 1 was diagnosed with a simultaneous leukoplakia and case study 2 developed an erythroleukoplakia following the primary tumor treatment...
September 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28883470/cytoglobin-promotes-cardiac-progenitor-cell-survival-against-oxidative-stress-via-the-upregulation-of-the-nf%C3%AE%C2%BAb-inos-signal-pathway-and-nitric-oxide-production
#4
Shuning Zhang, Xiuchun Li, Frances L Jourd'heuil, Shunlin Qu, Neil Devejian, Edward Bennett, David Jourd'heuil, Chuanxi Cai
Human cardiac stem/progenitor cells (hCPCs) may serve in regenerative medicine to repair the infarcted heart. However, this approach is severely limited by the poor survival of donor cells. Recent studies suggest that the mammalian globin cytoglobin (CYGB) regulates nitric oxide (NO) metabolism and cell death. In the present study, we found that CYGB is expressed in hCPCs. Through molecular approaches aimed at increasing or decreasing CYGB expression in hCPCs, we found that CYGB functions as a pro-survival factor in response to oxidative stress...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28881590/upregulation-of-microrna-125b-by-g-csf-promotes-metastasis-in-colorectal-cancer
#5
Xinghua Zhang, Xiao Ma, Huaying An, Changqing Xu, Wenjo Cao, Wei Yuan, Jie Ma
Although there are reports of miR-125b being dysregulated in colorectal cancer (CRC) and associated with CRC progression, little is known about its intrinsic regulatory mechanisms. Here we detected the expression of miR-125b in CRC tissues, subsequently investigated the effect of miR-125b on the proliferation, apoptosis, cell cycle and metastasis on CRC cells. Our results showed that the expression of miR-125b was significantly decreased in CRC tissues comparing to adjacent tissues. However, with the stimulation of Granulocyte colony-stimulating factor (G-CSF), which was highly expressed in CRC tissues, the expression of miR-125b could be improved...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28874163/expression-of-factors-involved-in-apoptosis-and-cell-survival-is-correlated-with-enzymes-synthesizing-lysophosphatidic-acid-and-its-receptors-in-granulosa-cells-originating-from-different-types-of-bovine-ovarian-follicles
#6
Emilia Sinderewicz, Katarzyna Grycmacher, Dorota Boruszewska, Ilona Kowalczyk-Zięba, Joanna Staszkiewicz, Tomasz Ślężak, Izabela Woclawek-Potocka
BACKGROUND: Lysophosphatidic acid (LPA) regulates reproductive processes in the cow. Ovarian granulosa cells play a pivotal role in follicle growth and development. Nevertheless, the role of LPA in the local regulation of granulosa cell function in different follicle categories in the bovine ovary has not been investigated. METHODS: Ovarian follicles were divided into healthy, transitional and atretic categories. The expression levels of AX, PLA2, LPARs and factors involved in apoptosis and cell survival processes in granulosa cells in different types of follicles were measured by real-time PCR...
September 6, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28865993/genetic-neutrophil-deficiency-ameliorates-cerebral-ischemia-reperfusion-injury
#7
Ryan A Frieler, Yutein Chung, Carolyn G Ahlers, George Gheordunescu, Jianrui Song, Thomas M Vigil, Yatrik M Shah, Richard M Mortensen
Neutrophils respond rapidly to cerebral ischemia and are thought to contribute to inflammation-mediated injury during stroke. Using myeloid Mcl1 knockout mice as a model of genetic neutrophil deficiency, we investigated the contribution of neutrophils to stroke pathophysiology. Myeloid Mcl1 knockout mice were subjected to transient middle cerebral artery occlusion and infarct size was assessed by MRI after 24h reperfusion. Immune cell mobilization and infiltration was assessed by flow cytometry. We found that myeloid Mcl1 knockout mice had significantly reduced infarct size when compared to heterozygous and wild type control mice (MyMcl1(+/+): 78...
August 31, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28861715/the-neuroprotective-transcription-factor-atf5-is-decreased-and-sequestered-into-polyglutamine-inclusions-in-huntington-s-disease
#8
Ivó H Hernández, Jesús Torres-Peraza, María Santos-Galindo, Eloísa Ramos-Morón, M Rosario Fernández-Fernández, María J Pérez-Álvarez, Antonio Miranda-Vizuete, José J Lucas
Activating transcription factor-5 (ATF5) is a stress-response transcription factor induced upon different cell stressors like fasting, amino-acid limitation, cadmium or arsenite. ATF5 is also induced, and promotes transcription of anti-apoptotic target genes like MCL1, during the unfolded protein response (UPR) triggered by endoplasmic reticulum stress. In the brain, high ATF5 levels are found in gliomas and also in neural progenitor cells, which need to decrease their ATF5 levels for differentiation into mature neurons or glia...
August 31, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28855351/non-hodgkin-and-hodgkin-lymphomas-select-for-overexpression-of-bclw
#9
Clare M Adams, Ramkrishna Mitra, Jerald Gong, Christine M Eischen
PURPOSE: B-cell lymphomas must acquire resistance to apoptosis during their development. We recently discovered BCLW, an anti-apoptotic BCL2 family member thought only to contribute to spermatogenesis, was overexpressed in diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. To gain insight into the contribution of BCLW to B-cell lymphomas and its potential to confer resistance to BCL2 inhibitors, we investigated the expression of BCLW and the other anti-apoptotic BCL2 family members in six different B-cell lymphomas...
August 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28797244/a-lowered-26s-proteasome-activity-correlates-with-mantle-lymphoma-cell-lines-resistance-to-genotoxic-stress
#10
Khaoula Ben Younes, Simon Body, Élodie Costé, Pierre-Julien Viailly, Hadjer Miloudi, Clémence Coudre, Fabrice Jardin, Fatma Ben Aissa-Fennira, Brigitte Sola
BACKGROUND: Mantle cell lymphoma (MCL) is a B-cell hemopathy characterized by the t(11;14) translocation and the aberrant overexpression of cyclin D1. This results in an unrestrained cell proliferation. Other genetic alterations are common in MCL cells such as SOX11 expression, mutations of ATM and/or TP53 genes, activation of the NF-κB signaling pathway and NOTCH receptors. These alterations lead to the deregulation of the apoptotic machinery and resistance to drugs. We observed that among a panel of MCL cell lines, REC1 cells were resistant towards genotoxic stress...
August 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28783166/anti-leukemic-activity-of-microrna-26a-in-a-chronic-lymphocytic-leukemia-mouse-model
#11
L D'Abundo, E Callegari, A Bresin, A Chillemi, B K Elamin, P Guerriero, X Huang, E Saccenti, E M A A Hussein, F Casciano, P Secchiero, G Zauli, G A Calin, G Russo, L J Lee, C M Croce, G Marcucci, S Sabbioni, F Malavasi, M Negrini
Dysregulation of microRNAs (miRNAs) plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL). The Eμ-TCL1 transgenic mouse develops a form of leukemia that is similar to the aggressive type of human B-CLL, and this valuable model has been widely used for testing novel therapeutic approaches. Here, we adopted this model to investigate the potential effects of miR-26a, miR-130an and antimiR-155 in CLL therapy. Improved delivery of miRNA molecules into CLL cells was obtained by developing a novel system based on lipid nanoparticles conjugated with an anti-CD38 monoclonal antibody...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28751770/enhancing-venetoclax-activity-in-acute-myeloid-leukemia-by-co-targeting-mcl1
#12
T-C Teh, N-Yn Nguyen, D M Moujalled, D Segal, G Pomilio, S Rijal, A Jabbour, K Cummins, K Lackovic, P Blombery, E Thompson, P G Ekert, G Lessene, S P Glaser, D C S Huang, A W Roberts, M A Guthridge, A H Wei
Targeted therapies are frequently combined with standard cytotoxic drugs to enhance clinical response. Targeting the BCL-2 family of proteins is an attractive option to combat chemoresistance in leukemia. Pre-clinical and clinical studies indicate modest single-agent activity with selective BCL-2 inhibitors (e.g. venetoclax). We show that venetoclax synergizes with cytarabine and idarubicin to increase anti-leukemic efficacy in a TP53 dependent manner. Although TP53 deficiency impaired sensitivity to combined venetoclax and chemotherapy, higher-dose idarubicin was able to suppress MCL1 and induce cell death independently of TP53...
July 28, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28723622/dual-targeting-of-mdm2-and-bcl2-as-a-therapeutic-strategy-in-neuroblastoma
#13
Alan Van Goethem, Nurten Yigit, Myrthala Moreno-Smith, Sanjeev A Vasudevan, Eveline Barbieri, Frank Speleman, Jason Shohet, Jo Vandesompele, Tom Van Maerken
Wild-type p53 tumor suppressor activity in neuroblastoma tumors is hampered by increased MDM2 activity, making selective MDM2 antagonists an attractive therapeutic strategy for this childhood malignancy. Since monotherapy in cancer is generally not providing long-lasting clinical responses, we here aimed to identify small molecule drugs that synergize with idasanutlin (RG7388). To this purpose we evaluated 15 targeted drugs in combination with idasanutlin in three p53 wild type neuroblastoma cell lines and identified the BCL2 inhibitor venetoclax (ABT-199) as a promising interaction partner...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28716899/hdac1-upregulation-by-nanog-promotes-multidrug-resistance-and-a-stem-like-phenotype-in-immune-edited-tumor-cells
#14
Kwon-Ho Song, Chel Hun Choi, Hyo-Jung Lee, Se Jin Oh, Seon Rang Woo, Soon-Oh Hong, Kyung Hee Noh, Hanbyoul Cho, Eun Joo Chung, Jae-Hoon Kim, Joon-Yong Chung, Stephen M Hewitt, Seungki Baek, Kyung-Mi Lee, Cassian Yee, Minjoo Son, Chih-Ping Mao, T C Wu, Tae Woo Kim
Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Immunoediting driven by antigen (Ag)-specific T cells enriches NANOG expression in tumor cells, resulting in a stem-like phenotype and immune resistance. Here, we identify HDAC1 as a key mediator of the NANOG-associated phenotype. NANOG upregulated HDAC1 through promoter occupancy, thereby decreasing histone H3 acetylation on K14 and K27. NANOG-dependent, HDAC1-driven epigenetic silencing of cell-cycle inhibitors CDKN2D and CDKN1B induced stem-like features...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28685948/role-of-zoledronic-acid-in-oncolytic-virotherapy-promotion-of-antitumor-effect-and-prevention-of-bone-destruction
#15
Yasuaki Yamakawa, Hiroshi Tazawa, Joe Hasei, Shuhei Osaki, Toshinori Omori, Kazuhisa Sugiu, Tadashi Komatsubara, Kouji Uotani, Tomohiro Fujiwara, Aki Yoshida, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara
Osteosarcoma is an aggressive malignant bone tumor that causes bone destruction. Although tumor-specific replicating oncolytic adenovirus OBP-301 induces an antitumor effect in an osteosarcoma tumor, it cannot prevent bone destruction. Zoledronic acid (ZOL) is a clinically available agent that inhibits bone destruction. In this study, we investigated the potential of combination therapy with OBP-301 and ZOL against osteosarcomas with bone destruction. The antitumor activity of OBP-301 and ZOL in monotherapy or combination therapy was assessed using three human osteosarcoma cell lines (143B, MNNG/HOS, SaOS-2)...
September 2017: Cancer Science
https://www.readbyqxmd.com/read/28670929/exploiting-the-pro-apoptotic-function-of-noxa-as-a-therapeutic-modality-in-cancer
#16
REVIEW
Jeroen E Guikema, Martine Amiot, Eric Eldering
Direct targeting of Bcl-2 members for therapeutic purposes in cancer has become a clinical reality with the FDA approval of ABT-199/Venetoclax. Other highly specific BH3-mimetics are in pre-clinical development. Understanding the functional interactions among the Bcl-2 family is of prime importance to fully exploit their potential. NOXA is considered a rather weak BH3-only member but it has unexplored potential in various settings, which are of relevance in cancer. NOXA is best known as a selective inhibitor of MCL1, itself overexpressed in many cancers, and this protein pair forms an important rheostat in many forms of cell stress...
August 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28668293/mechanisms-of-resistance-of-chemotherapy-in-early-stage-triple-negative-breast-cancer-tnbc
#17
Lironne Wein, Sherene Loi
Triple negative breast cancer (TNBC) a clinically aggressive subtype of breast cancer with poor outcomes. Chromosomal instability is a hallmark of many TNBCs, and likely underlies its ability to adapt and rapidly become resistant to chemotherapy. A study of residual disease after neoadjuvant chemotherapy have identified biological mechanisms driving this resistance to chemotherapy. Copy number amplifications such as MCL1, MYC and JAK2, as well as PTEN deletions or mutations have all been identified at a higher frequency in residual disease, suggesting they may play a role in de novo or acquired chemotherapy resistance...
August 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28659496/secretion-of-interleukin-6-by-bone-marrow-mesenchymal-stem-cells-promotes-metastasis-in-hepatocellular-carcinoma
#18
Fei Mi, Liansheng Gong
Mesenchymal stem cells (MSCs) interact with tumor cells and regulate tumorigenesis and metastasis. As one of the important components of the tumor microenvironment, MSC-secreted cytokines play a critical role in cancer development. However, whether and how bone marrow MSCs (BMSCs) and their secreted cytokines participate in hepatocellular carcinoma (HCC) progression, still remains largely unknown. In the present study, we first measured the concentration of interleukin-6 (IL-6) in BMSC conditioned medium (BMSC-CM)...
August 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28648936/diagnostic-pathology-of-alzheimer-s-disease-from-routine-microscopy-to-immunohistochemistry-and-experimental-correlations
#19
Gerard Nuovo, Bernard Paniccia, Louisa Mezache, Maria Quiñónez, James Williams, Paige Vandiver, Paolo Fadda, Vicky Amann
The absence of any histologic correlate for Alzheimer's disease despite its commonness and severe clinical sequelae may offers clues to its etiology. Recent evidence strongly suggests that the central event of this disease is the hyperphosphorylation of neuronal tau protein and not the beta amyloid precipitates. In each case, essential and soluble neuronal proteins derivatives form insoluble aggregates that can readily be detected by immunohistochemistry using antibodies specific for the misfolded proteins...
June 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28622513/comprehensive-and-integrative-genomic-characterization-of-hepatocellular-carcinoma
#20
(no author information available yet)
Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole-exome sequencing and DNA copy number analyses, and we analyzed 196 HCC cases by DNA methylation, RNA, miRNA, and proteomic expression also. DNA sequencing and mutation analysis identified significantly mutated genes, including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or downregulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed...
June 15, 2017: Cell
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