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https://www.readbyqxmd.com/read/28413418/study-of-the-regulatory-promoter-polymorphism-938c-a-of-b-cell-lymphoma-2-gene-in-breast-cancer-patients-of-mazandaran-province-in-northern-iran
#1
Sepideh Esfahani Moghaddam, Ali Barzegar, Novin Nikbakhsh
BACKGROUND: The incidence rate of breast cancer has been dramatically increasing since the last decade in Iran, and it is now one of the most common female malignant tumors. B-cell lymphoma 2 (BCL2) family is the most important regulator of apoptosis, and -938C>A single nucleotide polymorphism (SNP) of BCL2 gene promoter has been demonstrated to influence breast cancer susceptibility. In this research, we study the effect of -938C>A allelic variants on breast cancer risk in Mazandaran province at the North of Iran...
2017: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/28404587/cic-dux4-induces-small-round-cell-sarcomas-distinct-from-ewing-sarcoma
#2
Toyoki Yoshimoto, Miwa Tanaka, Mizuki Homme, Yukari Yamazaki, Yutaka Takazawa, Cristina R Antonescu, Takuro Nakamura
CIC-DUX4 sarcoma (CDS) or CIC-rearranged sarcoma is a  subcategory of small round cell sarcoma resembling the morphological phenotypes of Ewing sarcoma (ES). Hoever, recent clinicopathologic and molecular genetic analyses indicate that CDS is an independent disease entity from ES. Few ancillary markers have been used in the differential diagnosis of CDS, and additional CDS-specific biomarkers are needed for more definitive classification. Here we report the generation of an ex vivo mouse model for CDS by transducing embryonic mesenchymal cells (eMC) with human CIC-DUX4 cDNA...
April 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/28396364/novel-indole-based-tambjamine-analogues-induce-apoptotic-lung-cancer-cell-death-through-p38-mitogen-activated-protein-kinase-activation
#3
Pilar Manuel-Manresa, Luís Korrodi-Gregório, Elsa Hernando, Alberto Villanueva, David Martínez-García, Ananda M Rodilla, Ricard Ramos, Margarida Fardilha, Juan Moya, Roberto Quesada, Vanessa Soto-Cerrato, Ricardo Perez-Tomas
Lung cancer has become the leading killer cancer worldwide, due to late diagnosis and lack of efficient anticancer drugs. We have recently described novel natural-derived tambjamine analogues that are potent anion transporters capable of disrupting cellular ion balance, inducing acidification of the cytosol and hyperpolarization of cellular plasma membranes. Although these tambjamine analogues were able to compromise cell survival, their molecular mechanism of action remains largely unknown. Herein we characterize the molecular cell responses induced by highly active indole-based tambjamine analogues treatment in lung cancer cells...
April 10, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28381544/modulation-of-bax-and-mtor-for-cancer-therapeutics
#4
Rui Li, Chunyong Ding, Jun Zhang, Maohua Xie, Dongkyoo Park, Ye Ding, Guo Chen, Guojing Zhang, Melissa Gilbert-Ross, Wei Zhou, Adam Marcus, Shi-Yong Sun, Zhuo Georgia Chen, Gabriel L Sica, Suresh S Ramalingam, Andrew Magis, Haian Fu, Fadlo Khuri, Walter J Curran, Taofeek K Owonikoko, Dong M Shin, Jia Zhou, Xingming Deng
A rationale exists for pharmacologic manipulation of the serine (S)184 phosphorylation site of the proapoptotic Bcl2 family member Bax as an anticancer strategy. Here we report the refinement of the Bax agonist SMBA1 to generate CYD-2-11, which has characteristics of a suitable clinical lead compound. CYD-2-11 targeted the structural pocket proximal to S184 in the C-terminal region of Bax, directly activating its proapoptotic activity by inducing a conformational change enabling formation of Bax homooligomers in mitochondrial membranes...
April 5, 2017: Cancer Research
https://www.readbyqxmd.com/read/28381481/fkbp8-recruits-lc3a-to-mediate-parkin-independent-mitophagy
#5
Zambarlal Bhujabal, Åsa B Birgisdottir, Eva Sjøttem, Hanne B Brenne, Aud Øvervatn, Sabrina Habisov, Vladimir Kirkin, Trond Lamark, Terje Johansen
Mitophagy, the selective removal of damaged or excess mitochondria by autophagy, is an important process in cellular homeostasis. The outer mitochondrial membrane (OMM) proteins NIX, BNIP3, FUNDC1, and Bcl2-L13 recruit ATG8 proteins (LC3/GABARAP) to mitochondria during mitophagy. FKBP8 (also known as FKBP38), a unique member of the FK506-binding protein (FKBP) family, is similarly anchored in the OMM and acts as a multifunctional adaptor with anti-apoptotic activity. In a yeast two-hybrid screen, we identified FKBP8 as an ATG8-interacting protein...
April 5, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28379541/resistance-to-apoptosis-and-autophagy-leads-to-enhanced-survival-in-sertoli-cells
#6
Ferial Aslani, Tim Sebastian, Miguel Keidel, Suada Fröhlich, Hans-Peter Elsässer, Hans-Christian Schuppe, Jörg Klug, Poornima Mahavadi, Monika Fijak, Martin Bergmann, Andreas Meinhardt, Sudhanshu Bhushan
STUDY QUESTION: What is the underlying mechanism of Sertoli cell (SC) resistance to cell death? SUMMARY ANSWER: High expression of pro-survival B cell lymphoma-2 (BCL2) proteins and inhibition of apoptosis and autophagy prolongs SC survival upon exposure to stress stimuli. WHAT IS KNOWN ALREADY: In human and in experimental models of orchitis, tolerogenic SC survive stress conditions, while germ cells undergo massive apoptosis. In general, non-dividing highly differentiated cells tend to resist stress conditions for a longer time by favoring activation of pro-survival mechanisms and inhibition of cell death pathways...
April 3, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28371915/ag-205-a-pgrmc1-antagonist-ablates-progesterone-s-ability-to-block-oxidative-stress-induced-apoptosis-of-human-granulosa-luteal-cells
#7
Erica Anspach Will, Xiufang Liu, John J Peluso
The present studies were designed to determine whether progesterone (P4)-Progesterone Receptor Membrane Component 1 (PGRMC1) signaling is able to attenuate the apoptotic effects of oxidative stress induced by hydrogen peroxide (H2O2). To achieve this goal, freshly isolated human granulosa/luteal cells were maintained in culture. After several passages, the cells were treated with H2O2, which induced apoptosis within 2.5 h, while simultaneous treatment with P4 attenuated the apoptotic action of H2O2. AG 205, a PGRMC1 antagonist, eliminated P4's ability to prevent H2O2-induced apoptosis...
March 23, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28368400/interferon-%C3%AE-is-a-stat1-dependent-direct-inducer-of-bcl6-expression-in-imatinib-treated-chronic-myeloid-leukemia-cells
#8
H S Madapura, N Nagy, D Ujvari, T Kallas, M C L Kröhnke, S Amu, M Björkholm, L Stenke, P K Mandal, J S McMurray, M Keszei, L S Westerberg, H Cheng, F Xue, G Klein, E Klein, D Salamon
B-cell CLL/lymphoma 6 (BCL6) exerts oncogenic effects in several human hematopoietic malignancies including chronic myeloid leukemia (CML), where BCL6 expression was shown to be essential for CML stem cell survival and self-renewal during imatinib mesylate (IM) treatment. As several lines of evidence suggest that interferon γ (IFNγ) production in CML patients might have a central role in the response to tyrosine kinase inhibitor (TKI) therapy, we analyzed if IFNγ modulates BCL6 expression in CML cells. Although separate IFNγ or IM treatment only slightly upregulated BCL6 expression, combined treatment induced remarkable BCL6 upregulation in CML lines and primary human CD34+ CML stem cells...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28349834/downregulation-of-transcription-factor-gata4-sensitizes-human-hepatoblastoma-cells-to-doxorubicin-induced-apoptosis
#9
Tea Soini, Marjut Pihlajoki, Antti Kyrönlahti, Leif C Andersson, David B Wilson, Markku Heikinheimo
Hepatoblastoma, the most common type of pediatric liver cancer, is treated with a combination of surgery and chemotherapy. An essential drug in the treatment of hepatoblastoma is doxorubicin, which in high doses is cardiotoxic. This adverse effect is due to downregulation of cardiac expression of transcription factor GATA4, leading in turn to diminished levels of anti-apoptotic BCL2 (B-cell lymphoma 2) protein family members. GATA4 is also expressed in early fetal liver, but absent from normal postnatal hepatocytes...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28333095/cytosolic-bnip3-dimer-interacts-with-mitochondrial-bax-forming-heterodimers-in-the-mitochondrial-outer-membrane-under-basal-conditions
#10
Ulrike B Hendgen-Cotta, Sonja Esfeld, Katharina Rudi, Ilkka Miinalainen, Johann P Klare, Tienush Rassaf
The primary function of mitochondria is energy production, a task of particular importance especially for cells with a high energy demand like cardiomyocytes. The B-cell lymphoma (BCL-2) family member BCL-2 adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is linked to mitochondrial targeting after homodimerization, where it functions in inner membrane depolarization and permeabilization of the mitochondrial outer membrane (MOM) mediating cell death. We investigated the basal distribution of cardiac BNIP3 in vivo and its physical interaction with the pro-death protein BCL2 associated X, apoptosis regulator (BAX) and with mitochondria using immunoblot analysis, co-immunoprecipitation, and continuous wave and pulsed electron paramagnetic resonance spectroscopy techniques...
March 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28295185/dual-targeting-of-mcl1-and-noxa-as-effective-strategy-for-treatment-of-mantle-cell-lymphoma
#11
Elisabeth Höring, Arnau Montraveta, Simon Heine, Markus Kleih, Lea Schaaf, Matthias C Vöhringer, Anna Esteve-Arenys, Gael Roué, Dolors Colomer, Elias Campo, German Ott, Walter E Aulitzky, Heiko van der Kuip
Imbalances in the composition of BCL2 family proteins contribute to tumourigenesis and therapy resistance of mantle cell lymphoma (MCL), making these proteins attractive therapy targets. We studied the efficiency of dual targeting the NOXA/MCL1 axis by combining fatty acid synthase inhibitors (NOXA stabilization) with the CDK inhibitor Dinaciclib (MCL1 reduction). This combination synergistically induced apoptosis in cell lines and primary MCL cells and led to almost complete inhibition of tumour progression in a mouse model...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28294689/genomics-signaling-and-treatment-of-waldenstr%C3%A3-m-macroglobulinemia
#12
Zachary R Hunter, Guang Yang, Lian Xu, Xia Liu, Jorge J Castillo, Steven P Treon
Next-generation sequencing has revealed recurring somatic mutations in Waldenström macroglobulinemia (WM). Commonly recurring mutations include MYD88 (95% to 97%), CXCR4 (30% to 40%), ARID1A (17%), and CD79B (8% to 15%). Diagnostic discrimination of WM from overlapping B-cell malignancies is aided by MYD88 mutation status. Transcription is affected by MYD88 and CXCR4 mutations and includes overexpression of genes involved in VDJ recombination, CXCR4 pathway signaling, and BCL2 family members. Among patients with MYD88 mutations, those with CXCR4 mutations show transcriptional silencing of tumor suppressors associated with acquisition of mutated MYD88...
February 13, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28263292/the-master-role-of-microphthalmia-associated-transcription-factor-in-melanocyte-and-melanoma-biology
#13
Akinori Kawakami, David E Fisher
Certain transcription factors have vital roles in lineage development, including specification of cell types and control of differentiation. Microphthalmia-associated transcription factor (MITF) is a key transcription factor for melanocyte development and differentiation. MITF regulates expression of numerous pigmentation genes to promote melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis, including genes encoding proteins involved in apoptosis (eg, BCL2) and the cell cycle (eg, CDK2)...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28259821/inhibition-of-mapkinase-pathway-sensitizes-thyroid-cancer-cells-to-abt-737-induced-apoptosis
#14
Viswanath Gunda, Kristopher A Sarosiek, Eran Brauner, Yon Seon Kim, Salma Amin, Zhiheng Zhou, Antony Letai, Sareh Parangi
Bcl2 family proteins play an important role in the resistance of thyroid cancer cells to apoptosis induced by chemotherapeutic drugs and targeted therapies. BH3-profiling of seven fresh primary papillary thyroid cancer (PTC) tumors showed dependence for survival on Bcl-xL (2/7), Bcl2 (2/7), and Mcl-1 (2/7), while the majority of thyroid cell lines were mainly dependent on Bcl-xL. Targeting Bcl2 family proteins with the BH3 mimetic, ABT-737, while simultaneously inhibiting ERK pathway proteins with PLX4720 and PD325901 was shown to induce significantly high apoptosis in the majority of cell lines (8505c, SW1736, HTh7, BCPAP) and moderate apoptosis in the TPC-1 cell line...
June 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28223017/novel-bcl2-inhibitor-disarib-induces-apoptosis-by-disruption-of-bcl2-bak-interaction
#15
Supriya V Vartak, Divyaanka Iyer, T R Santhoshkumar, Sheetal Sharma, Archita Mishra, Gunaseelan Goldsmith, Mrinal Srivastava, Shikha Srivastava, Subhas S Karki, Avadhesha Surolia, Bibha Choudhary, Sathees C Raghavan
Apoptosis is a highly regulated pathway of programmed cell death relying on the fine balance between pro and antiapoptotic binding partners. Overexpression of the antiapoptotic protein BCL2 in several cancers makes it an ideal target for chemotherapy, with minimum side effects. In one of our previous studies, we designed, synthesized and characterized Disarib, a BCL2-specific small molecule inhibitor. Interestingly, Disarib showed a novel mode of BCL2 inhibition, by predominantly binding to its BH1 domain, as compared to the BH3-specific action of other known BCL2 inhibitors...
February 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28215535/ambra1-a-novel-bh3-like-protein-new-insights-into-the-ambra1-bcl2-family-proteins-relationship
#16
A Di Rita, F Strappazzon
Cellular homeostasis swings like a pendulum backward and forward between life and death. Two of the main processes, which regulate this equilibrium, are autophagy and apoptosis. While autophagy is a highly conserved self-digestion mechanism that mediates degradation of damaged or surplus components, apoptosis is a programmed cell suicide in which typical death signals induce the elimination of undesired cells. Both these processes are highly regulated by complex molecular machineries, including some common proteins whose "dual role" favors one process or the other...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28213497/mitochondrial-damage-elicits-a-tcdd-inducible-poly-adp-ribose-polymerase-mediated-antiviral-response
#17
Tatsuya Kozaki, Jun Komano, Daiki Kanbayashi, Michihiro Takahama, Takuma Misawa, Takashi Satoh, Osamu Takeuchi, Taro Kawai, Shigeomi Shimizu, Yoshiharu Matsuura, Shizuo Akira, Tatsuya Saitoh
The innate immune system senses RNA viruses by pattern recognition receptors (PRRs) and protects the host from virus infection. PRRs mediate the production of immune modulatory factors and direct the elimination of RNA viruses. Here, we show a unique PRR that mediates antiviral response. Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP ribose) polymerase (TIPARP), a Cysteine3 Histidine (CCCH)-type zinc finger-containing protein, binds to Sindbis virus (SINV) RNA via its zinc finger domain and recruits an exosome to induce viral RNA degradation...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28211974/whole-exome-sequencing-identified-1-base-pair-novel-deletion-in-bcl2-associated-athanogene-3-bag3-gene-associated-with-severe-dilated-cardiomyopathy-dcm-requiring-heart-transplant-in-multiple-family-members
#18
Muhammad Arshad Rafiq, Ayeshah Chaudhry, Melanie Care, Danna A Spears, Chantal F Morel, Robert M Hamilton
Dilated cardiomyopathy (DCM) is characterized by dilation and impaired contraction of the left ventricle or both ventricles. Among hereditary DCM, the genetic causes are heterogeneous, and include mutations encoding cytoskeletal, nucleoskeletal, mitochondrial, and calcium-handling proteins. We report three severely affected males, in a four-generation pedigree, with DCM phenotype who underwent cardiac transplant. Cardiomegaly with marked biventricular dilation and fibrosis were noticeable histopathological findings...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28182330/heat-shock-protein-27-hsp27-hspb1-is-synthetic-lethal-to-cells-with-oncogenic-activation-of-met-egfr-and-braf
#19
John David Konda, Martina Olivero, Daniele Musiani, Simona Lamba, Maria Flavia Di Renzo
The small Heat Shock Protein of 27 KDa (HSP27) is highly expressed in many cancers and is associated with aggressive tumor behaviour, metastasis, poor prognosis and resistance to chemotherapy. We aimed at assessing the role of HSP27 in modulating responses to target therapies. We selected several oncogene-addicted cancer cell lines, which undergo either cell cycle blockade or cell death in response to agents that target the specific oncogene. Surprisingly, HSP27 suppression alone resulted in the apoptotic death of MET-addicted EBC-1 lung cancer cells, EGFR-addicted colorectal carcinoma DiFi cells and BRAF-addicted colorectal carcinoma COLO205 and OXCO-1 and melanoma COLO741 cells, all of which also undergo death when treated with the specific targeted agent...
February 9, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28181540/hiv-related-proteins-prolong-macrophage-survival-through-induction-of-triggering-receptor-expressed-on-myeloid-cells-1
#20
Zhihong Yuan, Xian Fan, Bashar Staitieh, Chetna Bedi, Paul Spearman, David M Guidot, Ruxana T Sadikot
Triggering receptor expressed on myeloid cells-1(TREM-1) is a member of the superimmunoglobulin receptor family. We have previously shown that TREM-1 prolongs survival of macrophages treated with lipoolysaccharide through Egr2-Bcl2 signaling. Recent studies suggest a role for TREM-1 in viral immunity. Human immunodeficiency virus-1 (HIV) targets the monocyte/macrophage lineage at varying stages of infection. Emerging data suggest that macrophages are key reservoirs for latent HIV even in individuals on antiretroviral therapy...
February 9, 2017: Scientific Reports
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