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https://www.readbyqxmd.com/read/28618116/differences-in-p53-status-significantly-influence-the-cellular-response-and-cell-survival-to-1-25-dihydroxyvitamin-d3-metformin-cotreatment-in-colorectal-cancer-cells
#1
Mohamed A Abu El Maaty, Wendy Strassburger, Tooba Qaiser, Yasamin Dabiri, Stefan Wölfl
Mutations in the tumor suppressor p53 are highly prevalent in cancers and are known to influence the sensitivity of cells to various chemotherapeutics including the anti-cancer candidates 1,25-dihydrovitamin D3 [1,25D3] and metformin. Previous studies have demonstrated additive/synergistic anti-cancer effects of the 1,25D3-metformin combination in different models, however the influence of p53 status on the efficacy of this regimen has not been investigated. The CRC cell lines HCT116 wild-type (wt), HCT116 p53-/- and HT-29 (mutant; R273H) were employed, covering 3 different p53 variations...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28595732/the-novel-double-hit-t-8-22-q24-q11-myc-igl-and-t-14-15-q32-q24-igh-bcl2a1-in-diffuse-large-b-cell-lymphoma
#2
Takashi Akasaka, Chiyuki Kishimori, Katsuhiro Fukutsuka, Miho Nakagawa, Kayo Takeoka, Masahiko Hayashida, Gen Honjo, Hitoshi Ohno
An 82-year-old woman presented with generalized lymphadenopathy and skin involvement. Lymph node biopsy revealed diffuse large B-cell lymphoma with a high proliferation index. G-banding and fluorescence in situ hybridization showed a hypertetraploid karyotype with two copies of t(8;22)(q24;q11), generating the fusion of MYC and the immunoglobulin λ chain gene (IGL), and two copies of the novel immunoglobulin heavy chain gene (IGH) translocation, t(14;15)(q32;q24). A long-distance inverse polymerase chain reaction (PCR) using nested primer combinations designed for each constant gene of IGH showed that Cγ4 was juxtaposed to the downstream sequence of the BCL2A1 (BCL2-related protein A1) gene through the Sγ4 switch region...
August 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28595284/infertility-diagnosis-has-a-significant-impact-on-the-transcriptome-of-developing-blastocysts
#3
Blair R McCallie, Jason C Parks, Darren K Griffin, William B Schoolcraft, Mandy G Katz-Jaffe
STUDY QUESTION: Is the human blastocyst transcriptome associated with infertility diagnosis, specifically: polycystic ovaries (PCO), male factor (MF), and unexplained (UE)? SUMMARY ANSWER: The global blastocyst transcriptome was significantly altered in association with a PCO, MF, and UE infertility diagnosis. WHAT IS KNOWN ALREADY: Infertility diagnosis has an impact on the probability for a successful outcome following an IVF cycle. Limited information is known regarding the relationship between a specific infertility diagnosis and blastocyst transcription during pre-implantation development...
June 8, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28581513/kif26b-a-novel-oncogene-promotes-proliferation-and-metastasis-by-activating-the-vegf-pathway-in-gastric-cancer
#4
H Zhang, R-R Ma, X-J Wang, Z-X Su, X Chen, D-B Shi, X-Y Guo, H-T Liu, P Gao
Tumor metastasis is the main reason of cancer-related death for gastric cancer (GC) patients and gene expression microarray data indicate that kinesin family member 26B (KIF26B) is one of the most upregulated genes in metastatic GC samples. Specifically, KIF26B expression was upregulated in a stepwise manner from non-tumorous gastric mucosa, primary GC tissues without metastasis, via primary GC tissues with metastasis, to secondary lymph node metastatic (LNM) foci. Increased expression of KIF26B was correlated with tumor size, positive LNM or distant metastases and poor prognosis...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28579554/stat3-gain-of-function-mutations-associated-with-autoimmune-lymphoproliferative-syndrome-like-disease-deregulate-lymphocyte-apoptosis-and-can-be-targeted-by-bh3-mimetic-compounds
#5
Schafiq Nabhani, Cyrill Schipp, Hagit Miskin, Carina Levin, Sergey Postovsky, Tal Dujovny, Ariel Koren, Dan Harlev, Anne-Marie Bis, Franziska Auer, Baerbel Keller, Klaus Warnatz, Michael Gombert, Sebastian Ginzel, Arndt Borkhardt, Polina Stepensky, Ute Fischer
Autoimmune lymphoproliferative syndrome (ALPS) is typically caused by mutations in genes of the extrinsic FAS mediated apoptotic pathway, but for about 30% of ALPS-like patients the genetic diagnosis is lacking. We analyzed 30 children with ALPS-like disease of unknown cause and identified two dominant gain-of-function mutations of the Signal Transducer And Activator Of Transcription 3 (STAT3, p.R278H, p.M394T) leading to increased transcriptional activity. Hyperactivity of STAT3, a known repressor of FAS, was associated with decreased FAS-mediated apoptosis, mimicking ALPS caused by FAS mutations...
June 1, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28577205/a-preliminary-study-ps1-increases-u1-snrna-expression-associated-with-ad
#6
Zhi Cheng, Zhanqiang Du, Yingchun Shang, Yuling Zhang, Tao Zhang
U1 small nuclear RNA (snRNA) is selectively enriched in 100% of familial Alzheimer's disease (AD) resulting from presenilin1 (PS1) and amyloid precursor protein (APP) mutations. However, it remains unknown what gene or protein cause the U1 snRNA overexpression and then resulted in AD. Using SH-SY5Y cells, we discovered that PS1 induced the overexpression of U1 snRNA, which increased the production of Aβ. Moreover, the U1 snRNA overexpression induced the upregulation of apoe and clu transcripts. In addition, the levels of phosphorylation of tau protein at Thr212 were significantly elevated in U1 snRNA overexpression cells...
June 3, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28574506/role-of-atg5-dependent-cell-death-in-the-embryonic-development-of-bax-bak-double-knockout-mice
#7
Satoko Arakawa, Masatsune Tsujioka, Tatsushi Yoshida, Hajime Tajima-Sakurai, Yuya Nishida, Yosuke Matsuoka, Ikuyo Yoshino, Yoshihide Tsujimoto, Shigeomi Shimizu
Programmed cell death, which is required for the development and homeostasis of metazoans, includes mechanisms such as apoptosis, autophagic cell death, and necrotic (or type III) death. Members of the Bcl2 family regulate apoptosis, among which Bax and Bak act as a mitochondrial gateway. Although embryonic fibroblasts from Bax/Bak double-knockout (DKO) mice are resistant to apoptosis, we previously demonstrated that these cells die through an autophagy-dependent mechanism in response to various types of cellular stressors...
June 2, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28569785/cytoprotective-effect-of-neuropeptides-on-cancer-stem-cells-vasoactive-intestinal-peptide-induced-antiapoptotic-signaling
#8
Konduru S Sastry, Aouatef Ismail Chouchane, Ena Wang, George Kulik, Francesco M Marincola, Lotfi Chouchane
Cancer stem cells (CSCs) are increasingly considered to be responsible for tumor initiation, metastasis and drug resistance. The drug resistance mechanisms activated in CSCs have not been thoroughly investigated. Although neuropeptides such as vasoactive intestinal peptide (VIP) can promote tumor growth and activate antiapoptotic signaling in differentiated cancer cells, it is not known whether they can activate antiapoptotic mechanisms in CSCs. The objectives of this study are to unravel the cytoprotective effects of neuropeptides and identify antiapoptotic mechanisms activated by neuropeptides in response to anticancer drug treatment in CSCs...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28556798/loss-of-bax-by-mir-365-promotes-cutaneous-squamous-cell-carcinoma-progression-by-suppressing-apoptosis
#9
Liang Zhou, Ruirui Gao, Yinghui Wang, Meijuan Zhou, Zhenhua Ding
Pro-apoptotic BCL2 associated X (BAX) is traditionally thought to be regulated by anti-apoptotic BCL-2 family members, like BCL2-like 1 (BCL-XL), at the protein level. However, the posttranscriptional regulation of BAX is under explored. In this study, we identified BAX as the novel downstream target of miR-365, which is supported by gain- and loss-of-function studies of onco-miR-365. Loss of BAX by either RNA interference or highly-expressed miR-365 in cells of cutaneous squamous cell carcinoma (CSCC) enhanced the tumor resistance against apoptosis, while repressing cell proliferation, migration, and invasiveness...
May 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28504646/the-rna-binding-protein-tristetraprolin-schedules-apoptosis-of-pathogen-engaged-neutrophils-during-bacterial-infection
#10
Florian Ebner, Vitaly Sedlyarov, Saren Tasciyan, Masa Ivin, Franz Kratochvill, Nina Gratz, Lukas Kenner, Andreas Villunger, Michael Sixt, Pavel Kovarik
Protective responses against pathogens require a rapid mobilization of resting neutrophils and the timely removal of activated ones. Neutrophils are exceptionally short-lived leukocytes, yet it remains unclear whether the lifespan of pathogen-engaged neutrophils is regulated differently from that in the circulating steady-state pool. Here, we have found that under homeostatic conditions, the mRNA-destabilizing protein tristetraprolin (TTP) regulates apoptosis and the numbers of activated infiltrating murine neutrophils but not neutrophil cellularity...
June 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28499237/the-protective-effect-of-propofol-against-tnf-%C3%AE-induced-apoptosis-was-mediated-via-inhibiting-inos-no-production-and-maintaining-intracellular-ca-2-homeostasis-in-mouse-hippocampal-ht22-cells
#11
Zheng Xu, Yan Lu, Jiaqiang Wang, Xiaowei Ding, Jiawei Chen, Changhong Miao
AIM: Inflammation cytokine tumor necrosis factor-α (TNF-α) induces apoptosis in neuronal cells. We hypothesized that propofol may attenuate TNF-α-induced apoptosis in mouse hippocampal HT22 cells and aimed to explore the underlying mechanisms. METHODS: Mouse hippocampal HT22 cells were pretreated with propofol, and then stimulated with TNF-α. Cell viability was measured by cell counting kit 8 (CCK8). Cell apoptosis was examined by flow cytometry analysis. The effect of propofol on TNF-α-modulated nitric oxide production was measured by a nitrate reductase assay kit, intracellular calcium release and mitochondrial membrane potential (MMP) depolarization were measured by flow cytometry analysis, and the expression of inducible nitric oxide synthase (iNOS), C/EBP homologous protein (CHOP), B-cell lymphoma 2 (Bcl2) family and caspases were detected by Western blot...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28459364/cytotoxic-effect-of-celastrol-alone-or-in-combination-with-paclitaxel-on-anaplastic-thyroid-carcinoma-cells
#12
Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sung-Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin Lee
The influence of celastrol alone or in combination with paclitaxel on survival of anaplastic thyroid carcinoma cells was investigated. In 8505C and SW1736 cells, after treatment of celastrol, cell viability decreased, and cytotoxic activity increased. The protein levels of heat shock protein (hsp) 90, hsp70, Bax, death receptor 5, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase, phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-c-Jun N-terminal kinase (JNK) were elevated, and those of Bcl2, phospho-nuclear factor-kappaB (NF-κB), and total and phospho-Akt were reduced...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28454301/immunohistochemical-profile-of-ing3-protein-in-normal-and-cancerous-tissues
#13
Wen-Feng Gou, Xue-Feng Yang, Dao-Fu Shen, Shuang Zhao, Hong-Zhi Sun, Jun-Sheng Luo, Hua-Chuan Zheng
The inhibitor of growth family, member 3 (ING3) protein may be capable of blocking the cell cycle via activating p53-transactivated promoters of p21 and Bcl2-associated X protein, and may induce apoptosis via a Fas/caspase-8-dependent signaling pathway. In the present study, immunohistochemistry was performed in order to characterize the expression profile of ING3 protein in tissue microarrays containing mouse and human normal tissue, human hepatocellular (n=62), renal clear cell (n=62), pancreatic (n=62), esophageal squamous cell (n=45), cervical squamous cell (n=31), breast (n=144), gastric (n=196), colorectal (n=96), ovarian (n=208), endometrial (n=96) and lung carcinoma (n=192)...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28449207/targeting-anti-apoptotic-bcl2-family-proteins-in-haematological-malignancies-from-pathogenesis-to-treatment
#14
REVIEW
Meike Vogler, Harriet S Walter, Martin J S Dyer
The B-cell lymphoma 2 (BCL2) family of proteins comprise key regulators of apoptosis and are implicated in the pathogenesis of many malignancies, including lymphomas and leukaemias. Targeting of BCL2 proteins can be directly toxic to tumour cells or render them more sensitive to chemotherapy. Inhibition of the anti-apoptotic functions of BCL2 proteins using structure-based design to produce specific inhibitors of protein-protein interactions has been achieved for BCL2, MCL1 and BCL-XL (also termed BCL2L1), providing an armamentarium of new targeted therapies called BH3-mimetics...
April 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28439009/estrogen-receptor-%C3%AE-a-regulator-of-androgen-receptor-signaling-in-the-mouse-ventral-prostate
#15
Wan-Fu Wu, Laure Maneix, Jose Insunza, Ivan Nalvarte, Per Antonson, Juha Kere, Nancy Yiu-Lin Yu, Virpi Tohonen, Shintaro Katayama, Elisabet Einarsdottir, Kaarel Krjutskov, Yu-Bing Dai, Bo Huang, Wen Su, Margaret Warner, Jan-Åke Gustafsson
As estrogen receptor β(-/-) (ERβ(-/-)) mice age, the ventral prostate (VP) develops increased numbers of hyperplastic, fibroplastic lesions and inflammatory cells. To identify genes involved in these changes, we used RNA sequencing and immunohistochemistry to compare gene expression profiles in the VP of young (2-mo-old) and aging (18-mo-old) ERβ(-/-) mice and their WT littermates. We also treated young and old WT mice with an ERβ-selective agonist and evaluated protein expression. The most significant findings were that ERβ down-regulates androgen receptor (AR) signaling and up-regulates the tumor suppressor phosphatase and tensin homolog (PTEN)...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
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
#16
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
#17
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). However, 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
#18
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
#19
Rui Li, Chunyong Ding, Jun Zhang, Maohua Xie, Dongkyoo Park, Ye Ding, Guo Chen, Guojing Zhang, Melissa Gilbert-Ross, Wei Zhou, Adam I Marcus, Shi-Yong Sun, Zhuo G Chen, Gabriel L Sica, Suresh S Ramalingam, Andrew T Magis, Haian Fu, Fadlo R 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...
June 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28381481/fkbp8-recruits-lc3a-to-mediate-parkin-independent-mitophagy
#20
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...
June 2017: EMBO Reports
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