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Apoptosis modulation & Chemotherapy

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31 papers 25 to 100 followers
Wei Wei, Song Wu, Xiaolin Wang, Chris Kin-Wai Sun, Xiaoyang Yang, Xinrui Yan, Mei-Sze Chua, Samuel So
The molecular co-chaperone CDC37 is over-expressed in hepatocellular carcinoma (HCC) cells, where it functions with HSP90 to regulate the activity of protein kinases in multiple oncogenic signaling pathways that contribute towards hepatocarcinogenesis. Disruption of these signaling pathways via inhibition of HSP90/CDC37 interaction is therefore a rational therapeutic approach. We evaluated the anti-tumor effects of celastrol, pristimerin, and two novel derivatives (cel-D2, and cel-D7) on HCC cell lines in vitro and on orthotopic HCC patient-derived xenografts in vivo...
July 30, 2014: Oncotarget
N Aguiló, S Uranga, D Marinova, C Martín, J Pardo
Mycobacterium tuberculosis, the causative agent of tuberculosis, induces apoptosis in infected macrophages in vitro and in vivo. However, the molecular mechanism controlling this process is not known. In order to study the involvement of the mitochondrial apoptotic pathway in M. tuberculosis-induced apoptosis, we analysed cell death in M. tuberculosis-infected embryonic fibroblasts (MEFs) derived from different knockout mice for genes involved in this route. We found that apoptosis induced by M. tuberculosis is abrogated in the absence of Bak and Bax, caspase 9 or the executioner caspases 3 and 7...
2014: Cell Death & Disease
Magesh Muthu, Vino T Cheriyan, Sara Munie, Edi Levi, John Frank, Abdelkader E Ashour, Mandip Singh, Arun K Rishi
Neuroblastomas (NBs) are a clinically heterogeneous group of extra cranial pediatric tumors. Patients with high-risk, metastatic NBs have a long-term survival rate of below 40%, and are often resistant to current therapeutic modalities. Due to toxic side effects associated with radiation and chemotherapies, development of new agents is warranted to overcome resistance and effectively treat this disease in clinic. CARP-1 functional mimetics (CFMs) are an emerging class of small molecule compounds that inhibit growth of diverse cancer cell types...
2014: PloS One
Wei Wang, Jiang-Jiang Qin, Sukesh Voruganti, Ming-Hai Wang, Horrick Sharma, Shivaputra Patil, Jianwei Zhou, Hui Wang, Debabrata Mukhopadhyay, John K Buolamwini, Ruiwen Zhang
BACKGROUND & AIMS: The oncogene MDM2, which encodes an E3 ubiquitin ligase, is overexpressed in pancreatic cancers and is therefore a therapeutic target. Current inhibitors of MDM2 target the interaction between MDM2 and P53; these would have no effect on cancer cells that do not express full-length P53, including many pancreatic cancer cells. We searched for a compound that specifically inhibits MDM2 itself. METHODS: We performed a virtual screen and structure-based design to identify specific inhibitors of MDM2...
October 2014: Gastroenterology
Fu-Liang Bai, Yin-Hang Yu, Hui Tian, Gui-Ping Ren, Hui Wang, Bing Zhou, Xiao-Hui Han, Qing-Zhong Yu, De-Shan Li
Recombinant Newcastle disease virus (rNDV) have shown oncolytic therapeutic efficacy in preclinical studies and are currently in clinical trials. In this study, we have evaluated the possibility to enhance the cancer therapeutic potential of NDV by means of inserting both interleukin-2 (IL-2) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) delivered by rNDV. We demonstrated that rNDV expressing TRAIL (rNDV-TRAIL) or both human IL-2 and TRAIL (rNDV-IL-2-TRAIL) significantly enhanced inherent anti-neoplastic of rNDV by inducing apoptosis...
September 2014: Cancer Biology & Therapy
Chao-Ying Cheng, Yan-Yan Feng, Yi Zang, Jia Li, Xiao-Peng He, Guo-Rong Chen
A bis-triazolyl phenylalaninyl galactoside was synthesized by a two-fold click reaction between an azido phenylalanine and a di-O-propynyl galactoside. By a cytotoxicity assay the compound was determined to be selectively toxic for multiple myeloma (MM) among a series of cancer cell lines with no toxicity to a control cell line. A Western blot analysis suggested that this compound could potentiate the cleavage of poly ADP-ribose polymerase in MM cells, leading to apoptosis.
July 23, 2014: Carbohydrate Research
Xia Xue, Jin-Long Yu, De-Qing Sun, Feng Kong, Xian-jun Qu, Wen Zou, Jing Wu, Rong-Mei Wang
Curcumin, a polyphenol compound derived from the rhizome of the plant Curcuma longa L. has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms by which it induces apoptosis is limited. In this study, the anticancer efficacy of curcumin was investigated in human gastric adenocarcinoma SGC-7901 cells. The results demonstrated that curcumin induced morphological changes and decreased cell viability. Apoptosis triggered by curcumin was visualized using Annexin V-FITC/7- AAD staining...
2014: Asian Pacific Journal of Cancer Prevention: APJCP
Damien Moncelet, Pierre Voisin, Neha Koonjoo, Véronique Bouchaud, Philippe Massot, Elodie Parzy, Gérard Audran, Jean-Michel Franconi, Eric Thiaudière, Sylvain R A Marque, Paul Brémond, Philippe Mellet
Theranostics combines therapeutic and diagnostic or drug deposition monitoring abilities of suitable molecules. Here we describe the first steps of building an alkoxyamine-based theranostic agent against cancer. The labile alkoxyamine ALK-1 (t(1/2) = 50 min at 37 °C) cleaves spontaneously to generate (1) a highly reactive free alkyl radical used as therapeutic agents to induce cell damages leading to cell death and (2) a stable nitroxide used as contrast agent for Overhauser-enhanced magnetic resonance imaging (OMRI)...
July 7, 2014: Molecular Pharmaceutics
N Domanitskaya, J Wangari-Talbot, J Jacobs, E Peiffer, Y Mahdaviyeh, C Paulose, E Malofeeva, K Foster, K Q Cai, Y Zhou, B Egleston, E Hopper-Borge
BACKGROUND: Resistance to chemotherapeutic agents is a major obstacle to cancer treatment. A group of ABC efflux pumps, the Multidrug Resistance Proteins, is a source of resistance. Herein, we investigated the role of ABCC10 in mammary tumours, given the important role we have defined for ABCC10 in transporting taxanes, and the recognition that some ABCC proteins have roles in tumour growth. METHODS: ABCC10 expression was correlated to human breast cancer subtype using breast tissue microarrays...
August 12, 2014: British Journal of Cancer
Rumi Khandelia, Amit Jaiswal, Siddhartha Sankar Ghosh, Arun Chattopadhyay
The fabrication of a versatile nanocarrier based on agglomerated structures of gold nanoparticle (Au NP)-lysozyme (Lyz) in aqueous medium is reported. The carriers exhibit efficient loading capacities for both hydrophilic (doxorubicin) and hydrophobic (pyrene) molecules. The nanocarriers are finally coated with an albumin layer to render them stable and also facilitate their uptake by cancer cells. The interaction between agglomerated structures and the payloads is non-covalent. Cell viability assay in vitro showed that the nanocarriers by themselves are non-cytotoxic, whereas the doxorubicin-loaded ones are cytotoxic, with efficiencies higher than that of the free drug...
October 25, 2013: Small
A Shamas-Din, D Satsoura, O Khan, W Zhu, B Leber, C Fradin, D W Andrews
During apoptosis Bid and Bax are sufficient for mitochondrial outer membrane permeabilization, releasing pro-apoptotic proteins such as cytochrome c and Smac/Diablo into the cytoplasm. In most cells, both Bid and Bax are cytoplasmic but bind to mitochondrial outer membranes to exert pro-apoptotic functions. Binding to membranes is regulated by cleavage of Bid to truncated Bid (tBid), by conformation changes in tBid and Bax, and by interactions with other proteins. At least at the peripherally bound stage, binding is reversible...
2014: Cell Death & Disease
Xiao-Yan Zhao, Shen Yang, You-Ran Chen, Pei-Chun Li, Meng-Meng Dou, Jie Zhang
BACKGROUND AND AIMS: Arsenic trioxide (As2O3), which used as an effective agent in the treatment of leukaemia and other solid tumors, is largely limited by its toxicity. QT prolongation, torsades de pointes and sudden heart death have been implicated in the cardiotoxicity of As2O3. The present study was designed to explore whether the combination of As2O3 and resveratrol could generate a more powerful anti-cancer effect both in vitro and in vivo. MATERIALS AND METHODS: MTT assay was performed to assess the proliferation of Hela, MCF-7 and NB4 cells...
2014: PloS One
Katharina Belz, Hannah Schoeneberger, Sibylle Wehner, Andreas Weigert, Halvard Bönig, Thomas Klingebiel, Iduna Fichtner, Simone Fulda
Apoptosis resistance contributes to poor outcome in pediatric acute lymphoblastic leukemia (ALL). Here, we identify a novel synergistic combination of Smac mimetic BV6 and glucocorticoids (GCs) (ie, dexamethasone, prednisolone) to trigger apoptosis in ALL cells. BV6 and GCs similarly cooperate to induce apoptosis in patient-derived leukemia samples, underlining the clinical relevance. Importantly, BV6/dexamethasone cotreatment is significantly more effective than monotherapy to delay leukemia growth in a patient-derived xenograft model of pediatric ALL without causing additional side effects...
July 10, 2014: Blood
Longchuan Bai, David C Smith, Shaomeng Wang
Apoptosis is a tightly regulated cellular process and faulty regulation of apoptosis is a hallmark of human cancers. Targeting key apoptosis regulators with the goal to restore apoptosis in tumor cells has been pursued as a new cancer therapeutic strategy. XIAP, cIAP1, and cIAP2, members of inhibitor of apoptosis (IAP) proteins, are critical regulators of cell death and survival and are attractive targets for new cancer therapy. The SMAC/DIABLO protein is an endogenous antagonist of XIAP, cIAP1, and cIAP2. In the last decade, intense research efforts have resulted in the design and development of several small-molecule SMAC mimetics now in clinical trials for cancer treatment...
October 2014: Pharmacology & Therapeutics
Yanwei Qing, Haiyan Hu, Yuan Liu, Tao Feng, Wei Meng, Ling Jiang, Yongning Sun, Yang Yao
Berberine has multiple pharmacological activities, such as anti-oxidative, anti-inflammation and anticancer activity. It reduces the proliferation and induces apoptosis in the multiple myeloma cell line, U266. Here we explored the detailed mechanism by analysing the gene expression profiles in U266 treated with or without berberine. DNMT1 andDNMT3B, encoding for a highly conserved member of the DNA methyltransferases, decreased significantly. By dissection of biochemical network database (BNDB) with Kyoto Encyclopaedia of Genes and Genomes (KEGG) annotation, the p53 signalling pathway related genes were altered...
May 2014: Cell Biology International
S Fulda
Inhibitor of Apoptosis (IAP) proteins exert essential functions during tumorigenesis as well as treatment resistance by simultaneously blocking cell death pathways and promoting cell survival. As IAP proteins are typically aberrantly expressed in human cancers including hematological malignancies, they represent in principle promising targets for therapeutic interventions. There are currently exciting opportunities to rationally exploit the therapeutic targeting of IAP proteins for the treatment of leukemia and lymphoma...
July 2014: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Paul J H Lee, Dmitriy Rudenko, Michael A Kuliszewski, Christine Liao, M Golam Kabir, Kim A Connelly, Howard Leong-Poi
AIMS: The aim of this study was to investigate anti-apoptotic gene therapy using ultrasound-mediated plasmid delivery of survivin, an inhibitor of apoptosis protein, to prevent apoptosis and to attenuate left ventricular (LV) systolic dysfunction in a model of heart failure induced by doxorubicin. METHODS AND RESULTS: Effect of survivin transduction was investigated in vitro in rat cardiomyoblasts. After survivin transduction, survivin protein was detected in cell culture supernate confirming secretion of extracellular survivin...
March 1, 2014: Cardiovascular Research
Tetsuzo Tauchi, Masahiko Sumi, Akihiro Nakajima, Goro Sashida, Takashi Shimamoto, Kazuma Ohyashiki
PURPOSE: The near-universal emergence of imatinib resistance in patients with acute forms of Philadelphia chromosome-positive leukemia highlights the need for additional therapy to control this disease. G3139 (Genasense, oblimersen; Genta Inc.), a Bcl-2 antisense oligonucleotide, has been shown to down-regulate the Bcl-2 protein and induce apoptosis in myeloid leukemia cells from treated patients. We tested G3139 for its ability to inhibit BCR-ABL-mediated transformation in mice. EXPERIMENTAL DESIGN: Nude mice (n = 5/group) were transplanted s...
September 15, 2003: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
J M Matés, F M Sánchez-Jiménez
Reactive oxygen species are widely generated in biological systems. Consequently humans have evolved antioxidant defence systems that limit their production. Intracellular production of active oxygen species such as *OH, O2- and H2O2 is associated with the arrest of cell proliferation. Similarly, generation of oxidative stress in response to various external stimuli has been implicated in the activation of transcription factors and to the triggering of apoptosis. Here we review how free radicals induce DNA sequence changes in the form of mutations...
February 2000: International Journal of Biochemistry & Cell Biology
Alexei F Kisselev, Wouter A van der Linden, Herman S Overkleeft
Proteasomes are large, multisubunit proteolytic complexes presenting multiple targets for therapeutic intervention. The 26S proteasome consists of a 20S proteolytic core and one or two 19S regulatory particles. The 20S core contains three types of active sites. Many structurally diverse inhibitors of these active sites, both natural product and synthetic, have been discovered in the last two decades. One, bortezomib, is used clinically for treatment of multiple myeloma, mantle cell lymphoma, and acute allograft rejection...
January 27, 2012: Chemistry & Biology
2014-05-14 15:57:59
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