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BCL2 inhibition

Gaowu Hu, Wei Pen, Ming Wang
Tripartite motif-containing 14 (TRIM14) abnormally expressed in several human cancers. However, the function and expression of TRIM14 in human breast cancer were still largely unknown. To understand biological function of TRIM14 in breast cancer, we measured expression level of TRIM14. Cell proliferation and cell apoptosis were measured after TRIM14 overexpression or knockdown. The upregulation of TRIM14 was found in human breast cancer specimens and cell lines. Deduction of TRIM14 inhibited cell proliferation but increased cell apoptosis in BT474 and MDA-MB-231 cell lines...
March 21, 2018: Oncology Research
John F Seymour, Thomas J Kipps, Barbara Eichhorst, Peter Hillmen, James D'Rozario, Sarit Assouline, Carolyn Owen, John Gerecitano, Tadeusz Robak, Javier De la Serna, Ulrich Jaeger, Guillaume Cartron, Marco Montillo, Rod Humerickhouse, Elizabeth A Punnoose, Yan Li, Michelle Boyer, Kathryn Humphrey, Mehrdad Mobasher, Arnon P Kater
BACKGROUND: Venetoclax inhibits BCL2, an antiapoptotic protein that is pathologically overexpressed and that is central to the survival of chronic lymphocytic leukemia cells. We evaluated the efficacy of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. METHODS: In this randomized, open-label, phase 3 trial, we randomly assigned 389 patients to receive venetoclax for up to 2 years (from day 1 of cycle 1) plus rituximab for the first 6 months (venetoclax-rituximab group) or bendamustine plus rituximab for 6 months (bendamustine-rituximab group)...
March 22, 2018: New England Journal of Medicine
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
Zhaodi Zheng, Wenzhen Zhu, Bingwu Yang, Rongfei Chai, Tingting Liu, Fenglin Li, Guanghui Ren, Shuhua Ji, Shan Liu, Guorong Li
Metformin, a widely used antidiabetic drug, exhibits anticancer effects which are mediated by the phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT) signaling pathway. However, its use in anticancer therapy combined with other natural products remains unclear. Flavone as the core structure of flavonoids has been demonstrated to induce cell apoptosis without causing serious side effect. Murine double minute X (MDMX) inhibits tumor suppressor gene p53 whose function is associated with the PI3K/AKT pathway...
April 2018: Oncology Letters
Shuo Tu, Xia-Li Zhang, Hui-Fang Wan, Yan-Qin Xia, Zhuo-Qi Liu, Xiao-Hong Yang, Fu-Sheng Wan
To investigate the effects of taurine on cell proliferation and apoptosis, the human lung cancer A549 cell line and xenograft tumors in nude mice were used. The effects of taurine on cell proliferation and apoptosis were observed at time points of 24, 48 and 72 h after treatment using an MTT assay to detect the survival rate, and flow cytometry to detect the apoptotic rate. Western blot analysis was performed to examine the levels of p53 upregulated modulator of apoptosis (PUMA), BCL2, apoptosis regulator (Bcl-2) and BCL2-associated X, apoptosis regulator (Bax) in A549 cells...
April 2018: Oncology Letters
Bo Diao, Ying Liu, Guo-Zheng Xu, Yi Zhang, Jun Xie, Jie Gong
Galectin-3 (Gal-3), a β-galactoside-binding protein, has been implicated in cell proliferation, cell adhesion, and the progression and metastasis of various types of cancer. The present study investigated the involvement of Gal-3 in the tumorigenesis and progression of pituitary tumors using three rat pituitary tumor cell lines. Following transfection with Gal-3 expression and interference vectors, the impact of Gal-3 on proliferation, apoptosis and migration of pituitary tumor cells was been investigated...
April 2018: Oncology Letters
Tao Wang, Hui Zhao, Hua Gao, Changming Zhu, Yao Xu, Liping Bai, Junbo Liu, Feng Yan
The mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways are activated during pathogenesis of gastrointestinal stromal tumors (GISTs). Forkhead box protein O1 (FOXO1) is a transcription factor regulated by the MAPK and PI3K pathways and is associated with multiple metabolic reactions. The present study aims to investigate the association of FOXO1 with cell proliferation and apoptosis in the cell line, GIST-T1. Cell counting kit-8 assay revealed that cell growth was inhibited by the PI3K inhibitor, LY294002, and/or MAPK inhibitor, UO126...
April 2018: Experimental and Therapeutic Medicine
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 microRNA (miRNA)-based therapies against colorectal cancer (CRC). In this study, we aimed to clarify a value of miR-29b-1-5p as a next generation treatment, especially for KRAS mutant CRC. RT-PCR assay showed that expression of miR-29b-3p was high and its partner strand, miR-29b-1-5p level was only negligible in clinical CRC samples. Mimic-miR-29b-1-5p significantly inhibited proliferation of KRAS mutant CRC cell lines DLD1 and SW480 and KRAS wild type HT29 cells...
March 15, 2018: Molecular Cancer Therapeutics
Yuzhuo Chen, Weiliang Song
The present study assessed the association between the Wnt/catenin β1 (CTNNB1)/microRNA (miR)183 signaling pathway and the recurrence and prognosis of colorectal cancer. The expression of Wnt, CTNNB1 and miR183 in primary colorectal cancer tissue was increased compared with that in the paracarcinoma tissue. Disease-free survival and overall survival were decreased in patients with colorectal cancer and increased miR183 expression compared with those in patients with colorectal cancer and decreased miR183 expression...
April 2018: Oncology Letters
Mas Sahidayana Mokhtar, Wan Safwani Wan Kamarul Zaman, Thamil Selvee Ramasamy
BACKGROUND: Konjac glucomannan (KGM) is a water-soluble dietary fibre extracted from Amorphophallus konjac K. Koch (Araceae). Konjac fibre has been clinically proven as an effective antioxidant agent in weight control but its traditionally known tumour suppression property remains to be explored. OBJECTIVE: The main objective of this study is to determine the potential anti-proliferative effect of KGM on cancer and normal human liver cell lines, HepG2 and WRL68, respectively...
March 7, 2018: Anti-cancer Agents in Medicinal Chemistry
Sadegh Fattahi, Elham Ghadami, Mohsen Asouri, Ali Motevalizadeh Ardekanid, Haleh Akhavan-Niaki
Breast cancer is a heterogeneous and multifactorial disease with variable disease progression risk, and treatment response. Urtica dioica is a traditional herb used as an adjuvant therapeutic agent in cancer. In the present study, we have evaluated the effects of the aqueous extract of Urtica dioica on Adenosine deaminase (ADA) and Ornithine decarboxylase (ODC1) gene expression in MCF-7, MDA-MB-231, two breast cancer cell lines being estrogen receptor positive and estrogen receptor negative, respectively.  Cell lines were cultured in suitable media...
February 28, 2018: Cellular and Molecular Biology
Wan Wang, Di Wen, Weisong Duan, Juntao Yin, Can Cui, Ying Wang, Zhongyao Li, Yakun Liu, Chunyan Li
Amyotrophic lateral sclerosis (ALS) is closely associated with a reduction of neurotrophic factors in the central nervous system (CNS). Insulin-like growth factor 1 (IGF1)-encoding vectors delivered via intramuscular and intraparenchymal spinal cord injections have conferred therapeutic benefits in ALS model mice, although the development of a noninvasive delivery route is still needed. Intravenous administration of adeno-associated virus (AAV) vectors has been used to induce expression of neurotrophic genes in the lumbar spinal cords of adult mice...
February 27, 2018: Brain Research Bulletin
Suresh Banjara, Jiahao Mao, Timothy M Ryan, Sofia Caria, Marc Kvansakul
Programmed cell death or apoptosis is a critical mechanism for the controlled removal of damaged or infected cells, and proteins of the BCL-2 family are important arbiters of this process. Viruses have been shown to encode functional and structural homologs of BCL-2 to counter premature host-cell apoptosis and ensure viral proliferation or survival. Grouper iridovirus (GIV) is a large DNA virus belonging to the Iridoviridae family and harbors GIV66, a putative BCL-2 like protein and mitochondrially localized apoptosis inhibitor...
February 26, 2018: Journal of Biological Chemistry
Jana Mihalyova, Tomas Jelinek, Katerina Growkova, Matous Hrdinka, Michal Simicek, Roman Hajek
Inhibitors of anti-apoptotic proteins of the BCL2 family can successfully restart the deregulated process of apoptosis in malignant cells. While non-selective agents have been limited by their affinity to different BCL2 members, and thus inducing excessive toxicity, the highly selective BCL2 inhibitor, venetoclax (ABT-199, Venclexta™), has an acceptable safety profile. To date, it has been approved in monotherapy for the treatment of relapsed or refractory chronic lymphocytic leukaemia (CLL) with 17p deletion...
February 22, 2018: Experimental Hematology
Zekrayat J H Medras, Norhan M El-Sayed, Sawsan A Zaitone, Eman A Toraih, Manal M Sami, Yasser M Moustafa
BACKGROUND: Glutamine aminoacid regulates insulin exocytosis from pancreatic β-cells. Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has fascinated function in inhibiting β-cell apoptosis and preserving pancreatic β-cell mass. The present study investigated the benefit of adding glutamine to a regimen of liraglutide in diabetic rats focusing on their role in increasing insulin production and upregulation of the expression of sodium-dependent neutral aminoacid transporter-2 (SNAT2)...
October 25, 2017: Pharmacological Reports: PR
Carmen D Herling, Nima Abedpour, Jonathan Weiss, Anna Schmitt, Ron Daniel Jachimowicz, Olaf Merkel, Maria Cartolano, Sebastian Oberbeck, Petra Mayer, Valeska Berg, Daniel Thomalla, Nadine Kutsch, Marius Stiefelhagen, Paula Cramer, Clemens-Martin Wendtner, Thorsten Persigehl, Andreas Saleh, Janine Altmüller, Peter Nürnberg, Christian Pallasch, Viktor Achter, Ulrich Lang, Barbara Eichhorst, Roberta Castiglione, Stephan C Schäfer, Reinhard Büttner, Karl-Anton Kreuzer, Hans Christian Reinhardt, Michael Hallek, Lukas P Frenzel, Martin Peifer
Deciphering the evolution of cancer cells under therapeutic pressure is a crucial step to understand the mechanisms that lead to treatment resistance. To this end, we analyzed whole-exome sequencing data of eight chronic lymphocytic leukemia (CLL) patients that developed resistance upon BCL2-inhibition by venetoclax. Here, we report recurrent mutations in BTG1 (2 patients) and homozygous deletions affecting CDKN2A/B (3 patients) that developed during treatment, as well as a mutation in BRAF and a high-level focal amplification of CD274 (PD-L1) that might pinpoint molecular aberrations offering structures for further therapeutic interventions...
February 20, 2018: Nature Communications
Nathaniel Robichaud, Brian E Hsu, Roman Istomine, Fernando Alvarez, Julianna Blagih, Eric H Ma, Sebastian V Morales, David L Dai, Glenn Li, Margarita Souleimanova, Qianyu Guo, Sonia V Del Rincon, Wilson H Miller, Santiago Ramón Y Cajal, Morag Park, Russell G Jones, Ciriaco A Piccirillo, Peter M Siegel, Nahum Sonenberg
The translation of mRNAs into proteins serves as a critical regulatory event in gene expression. In the context of cancer, deregulated translation is a hallmark of transformation, promoting the proliferation, survival, and metastatic capabilities of cancer cells. The best-studied factor involved in the translational control of cancer is the eukaryotic translation initiation factor 4E (eIF4E). We and others have shown that eIF4E availability and phosphorylation promote metastasis in mouse models of breast cancer by selectively augmenting the translation of mRNAs involved in invasion and metastasis...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Mangesh H Kaulage, Basudeb Maji, Sanjeev Pasadi, Asfa Ali, Santanu Bhattacharya, K Muniyappa
Recent studies support the idea that G-quadruplex structures in the promoter regions of oncogenes and telomere DNA can serve as potential therapeutic targets in the treatment of cancer. Accordingly, several different types of organic small molecules that stabilize G-quadruplex structures and inhibit telomerase activity have been discerned. Here, we describe the binding of benzimidazole-carbazole ligands to G-quadruplex structures formed in G-rich DNA sequences containing the promoter regions of human c-MYC, c-KIT1, c-KIT2, VEGF and BCL2 proto-oncogenes...
February 5, 2018: European Journal of Medicinal Chemistry
Yi Lu, Dongdong Lu, Yu Hu
OBJECTIVES: Glucagon-like peptide 2 (GLP2) is involved in the regulation of energy absorption and metabolism. Despite the importance of the GLP2 signalling mechanisms on osteoclast, little has been studied on how GLP2 works during osteoclastogenesis. MATERIALS AND METHODS: RAW264.7 cells were infected with rLV-Green-GLP2. The induction of osteoclasts was performed by RANKL. TRAP were detected by RT-PCR, Western blotting and staining. Total nitric oxide and total NOS activity were measured...
February 19, 2018: Cell Proliferation
Sharada H Sharma, Jayasurya Suresh Kumar, David Raj Chellappan, Sangeetha Nagarajan
Colorectal cancer is the third most common cancer worldwide. The development of effective, inexpensive and safe chemopreventive agents would be of great benefit as it involves use of natural products to prevent or suppress the progression of precursor lesions. Morin a flavonoid found in figs (Ficus carica) and other plants is shown to inhibit 1,2-dimethylhydrazine (DMH) induced colon cancer progression in a short term and long term model of colon cancer rats; however, the molecular target for the colon cancer chemoprotective efficacy of morin is yet to be discovered...
February 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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