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https://www.readbyqxmd.com/read/28710745/the-pan-bcl2-inhibitor-at101-activates-the-intrinsic-apoptotic-pathway-and-causes-dna-damage-in-acute-myeloid-leukemia-stem-like-cells
#1
Leisi Zhang, Yong Zhou, Kai Chen, Pengcheng Shi, Yin Li, Manman Deng, Zhiwu Jiang, Xiangmeng Wang, Peng Li, Bing Xu
BACKGROUND: Leukemia stem cells (LSCs) are considered to be the cause of treatment failure and relapse in acute myeloid leukemia (AML). Overexpression of the Bcl-2 family of anti-apoptotic proteins such as Bcl-2, Bcl-xl, and Mcl-1 accounts for survival and self-renewal of LSCs. AT101 binds to the BH3 motif of all Bcl-2 family anti-apoptotic proteins and demonstrates anti-tumor activity in multiple types of tumor. Thus, we hypothesized that this agent might have the potential to deplete LSCs...
July 14, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28709980/downregulation-of-usp18-inhibits-growth-and-induces-apoptosis-in-hepatitis-b-virus-related-hepatocellular-carcinoma-cells-by-suppressing-bcl2l1
#2
Jing Cai, Tiande Liu, Xiaoliu Jiang, Changkuo Guo, Anwen Liu, Xinlan Xiao
Ubiquitin-specific peptidase 18 (USP18) is closely related with hepatitis B virus (HBV), which has been involved in tumourigenesis. However, there has been little research into the role of USP18 on the progression of hepatocellular carcinoma (HCC), especially in HBV-related HCC. In present study, we found that USP18 expression was aberrantly elevated in HCC tissues than adjacent non-tumour tissues. Importantly, USP18 expression was higher in HBV-related HCC cell lines (HepG2.2.15 and Hep3B) than HBV-unrelated HCC cell lines...
July 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28689336/v79-fibroblasts-are-protected-against-reactive-oxygen-species-by-flax-fabric
#3
Katarzyna Skórkowska-Telichowska, Anna Kulma, Tomasz Gębarowski, Wioleta Wojtasik, Kamil Kostyn, Helena Moreira, Anna Szyjka, Aleksandra Boba, Marta Preisner, Justyna Mierziak, Malgorzata Arendt, Anna Kostyn, Michał Szatkowski, Jan Szopa, Kazimierz Gąsiorowski
Chinese hamster pulmonary fibroblasts (V79 cells) pre-treated with flax fabrics derived from non-modified or genetically engineered flax fibres and treated with H2O2 revealed a markedly lower level of intracellular reactive oxygen species (ROS) than control, non-pre-treated cells. The fabrics were prepared from fibres derived from two kinds of transgenic plants: W92 plants, which overproduce flavonoids, and M type plants, which produce hydroxybutyrate polymer in their vascular bundles and thus in fibres. Incubating the V79 cells with the flax fabrics prior to H2O2 treatment also reduced the amount of DNA damage, as established using the comet assay (also known as alkaline single-cell gel electrophoresis) and pulsed-field electrophoresis of intact cellular DNA...
July 8, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28684422/curcumin-shifts-ras-induced-pro-proliferative-mek-erk-signaling-toward-pro-apoptotic-p38mapk-jnk1-signaling-triggering-p53-activation-and-apoptosis
#4
Shuvomoy Banerjee, Pushpak Bhattacharjee, Juni Chakraborty, Abir K Panda, Arnab Bandyopadhyay, Suman K Banik, Gaurisankar Sa
Oncogenic RAS is primarily associated with potent mitogenic ability, and RAS mutants also have an apoptogenic activity, which is poorly understood. Therefore, exploring the signaling circuit that shifts RAS-signals from pro-proliferative to death pathways may provide some molecular clues to the missing link between the mitogenic and apoptogenic mechanisms. Here, we used a systems biology approach exploiting microarray data and employing a mathematical model to better understand the dual role of oncogenic RAS This approach revealed that a curcumin-based intervention shifts the oncogenic RAS-induced MEK/ERK pro-proliferative pathway toward p38MAPK/JNK1 pro-death signaling...
July 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28672935/next-generation-sequencing-reveals-lymph-node-metastasis-associated-genetic-markers-in-colorectal-cancer
#5
Ni Xie, Yujiang Yao, Lili Wan, Ting Zhu, Litao Liu, Jianhui Yuan
Colorectal cancer is the third most prevalent type of cancer in the United States. Early diagnosis of lymph node metastases is essential to improve the prognosis for patients with colorectal cancer. Therefore, the present study aimed to screen genetic markers, including single nucleotide polymorphisms (SNPs), copy number variations (CNVs) and mRNA expression, associated with lymph node metastases in patients with colorectal cancer to enable an early diagnosis. Targeted next-generation sequencing was applied to capture SNPs and CNVs in tumor-related candidate genes within tumor tissues from 39 colorectal cancer patients; reverse transcription-quantitative polymerase chain reaction was used to detect the specific mRNA level of tumor-related candidate genes, including vascular endothelial growth factor C, cyclin-A2, Interleukin-2, ATP-binding cassette sub-family G member 2, epidermal growth factor (EGF) and nuclear factor kappa B subunit 1 (NFKB1) on chromosome 4...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28656307/sirt6-inhibits-growth-of-gastric-cancer-by-inhibiting-jak2-stat3-pathway
#6
Jianmei Zhou, Ang Wu, Xiaoting Yu, Jianwei Zhu, Hui Dai
SIRT6, a member of NAD positivity-dependent class III deacetylase sirtuin family, played versatile roles in human cancers. However, the expression and biological function of SIRT6 in gastric cancer (GC) remain to be investigated. In this study, we found that SIRT6 expression level was decreased in gastric cancer tissues and cell lines. Decreased SIRT6 expression was associated with unfavorable clinical parameters including tumor differentiation, tumor size and TNM stage. Importantly, decreased level of SIRT6 was associated with decreased rate of overall survival (OS) and disease‑free survival (DFS)...
June 27, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28653878/sirtuin-6-plays-an-oncogenic-role-and-induces-cell-autophagy-in-esophageal-cancer-cells
#7
Nan Huang, Zhiwei Liu, Jiabei Zhu, Zhongqi Cui, Yuguang Li, Yongchun Yu, Fenyong Sun, Qiuhui Pan, Qingyuan Yang
Sirtuin 6, a member of sirtuin family, is generally regarded as a tumor suppressor as it participates in suppressing hypoxia-inducible factor 1α and MYC transcription activity by deacetylating H3K9 (histone H3 lysine 9) and H3K56 (histone H3 lysine) at promoters of target genes, leading to the aerobic glycolysis inhibition and cell growth suppression. However, its expression has recently been reported to be highly elevated in a series of tumors, including prostate cancer, breast cancer, and non-small cell lung cancer, indicating that sirtuin 6 plays dual roles in tumorigenicity in a cell/tumor type-specific manner...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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