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Apoptosis therapy

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https://www.readbyqxmd.com/read/29236324/silencing-of-phospholipase-c-gamma-2-promotes-proliferation-of-rat-hepatocytes-in-vitro
#1
Xiaoguang Chen, Xuemin Zhu, Yumei Liu, Qiongxia Lv, Jun Ma
The management of hepatic failure is undoubtedly difficult, and poor results have led to the search for novel therapeutic approaches. Nowadays, anti-apoptotic gene therapy is considered as an ideal approach. It has been proved that phospholipase Cγ2 (PLCγ2) is involved in the apoptosis of immune cells and tumor cells; however, whether this gene is related to hepatocyte death is still unclear. This study examined the role of PLCγ2 by inhibiting its expression in rat hepatocytes with siRNA. We also further analyzed the cellular mechanism by which the expression inhibition of PLCγ2 induces cell death...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29236308/database-of-transcription-factors-in-lung-cancer-dbtflc-a-novel-resource-for-exploring-transcription-factors-associated-with-lung-cancer
#2
A Thabitha, Ameya Athul Dravid, Riya Tripathi, S Sajitha Lulu
Lung cancer is considered as the most prevalent form of cancer and it is found to be frequent cause of cancer related death. Even though, approved molecular targeted therapies other than chemotherapy are currently unavailable, the mechanism of pathogenesis in lung cancer remains still unclear. Transcription factors (TFs) play a critical role in cancer cell processes, such as cell proliferation, apoptosis, migration, and regulate gene expression. Thus, the identification and characterization of transcription factors involved in lung cancer would provide valuable information for further elucidation of the mechanism(s) underlying pathogenesis and the identification of potential therapeutic target types, which are critical for the development of therapeutic strategies...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29235276/-anti-tumor-target-identification-and-molecular-mechanism-study-of-total-saponins-from-albizia-julibrissin
#3
Yi Qian, Qing-Hua Han, Dan Liu, Peng-Fei Tu, Ke-Wu Zeng, Hong Liang
Dried stem bark from Albizia julibrissin(AJ) is a common traditional Chinese herb with several therapy effects including insomnia, anxiety and anti-tumor. Recently, the anti-tumor effect and mechanism studies of AJ have drawn much attention; however, there are still some troubles in chemical composition separation, which leads to the difficulties in pharmacological research of AJ. In this study, we firstly confirmed the proliferation inhibitory effect of total saponins from AJ(TSAJ)on human hepatocarcinoma(HepG2) cells, and also tested the apoptosis induction effect of TSAJ...
October 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29235249/anticancer-effects-of-resveratrol-in-canine-hemangiosarcoma-cell-lines
#4
A Carlson, K S Alderete, M K O Grant, D M Seelig, L C Sharkey, B N M Zordoky
Hemangiosarcoma (HSA) is a highly malignant tumour with aggressive biological behaviour. HSAs are more common in dogs than other domestic animals. The median survival time of dogs with HSA remains short, even with chemotherapy and surgery. Therefore, there is a critical need to improve the adjuvant chemotherapeutic regimens to improve clinical outcomes in dogs with HSA. Resveratrol has been shown to possess strong anti-proliferative and/or pro-apoptotic properties in human cancer cell lines. Nevertheless, the potential anticancer effects of resveratrol have not been reported in canine HSAs...
December 13, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/29234489/molecular-insights-suppression-of-egfr-and-akt-activation-by-a-small-molecule-in-non-small-cell-lung-cancer
#5
Balaji Chandrasekaran, Ashish Tyagi, Arun K Sharma, Lu Cai, Murali Ankem, Chendil Damodaran
Epidermal growth factor receptor (EGFR) activation events and the mammalian target of rampamycin (mTOR) are considered important therapeutic targets in alleviating cancer conditions. The current treatment paradigm has shifted to personalized treatment strategies with tyrosine kinase inhibitors (TKIs) or anaplastic lymphoma kinase (ALK) inhibitors, due to low survival rates in non-small cell lung cancer (NSCLC) in terms of the prevailing platinum-based therapy. In the present study, we examined the anticancer potential of Verrucarin J (VJ), a small molecule, in NSCLC cell lines (H460 and A549)...
September 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29233971/implication-of-4e-bp1-protein-dephosphorylation-and-accumulation-in-pancreatic-cancer-cell-death-induced-by-combined-gemcitabine-and-trail
#6
Androulla Elia, Ricky Henry-Grant, Charlotte Adiseshiah, Catherine Marboeuf, Rebecca J Buckley, Michael J Clemens, Satvinder Mudan, Stéphane Pyronnet
Pancreatic cancer cells show varying sensitivity to the anticancer effects of gemcitabine. However, as a chemotherapeutic agent, gemcitabine can cause intolerably high levels of toxicity and patients often develop resistance to the beneficial effects of this drug. Combination studies show that use of gemcitabine with the pro-apoptotic cytokine TRAIL can enhance the inhibition of survival and induction of apoptosis of pancreatic cancer cells. Additionally, following combination treatment there is a dramatic increase in the level of the hypophosphorylated form of the tumour suppressor protein 4E-BP1...
December 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29233905/neddylation-blockade-diminishes-hepatic-metastasis-by-dampening-cancer-stem-like-cells-and-angiogenesis-in-uveal-melanoma
#7
Yanli Jin, Ping Zhang, Yun Wang, Bei Jin, Jingfeng Zhou, Jing Zhang, Jingxuan Pan
PURPOSE: Liver metastasis is the major and direct cause of death in patients with uveal melanoma (UM). There is no effective therapy for patients with metastatic UM. Improved treatments of hepatic metastatic patients with UM were urgently needed. Inspired by readily detectable key components in neddylation pathway in UM cells, we aimed at exploring whether neddylation pathway was a therapeutic target for liver metastatic UM. EXPERIMENTAL DESIGN: Expression of key proteins in neddylation pathway in UM was detected by Western blotting, real-time quantitative RT-PCR (qRT-PCR), and immunohistochemical staining...
December 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29233541/combination-therapies-targeting-hdac-and-ikk-in-solid-tumors
#8
REVIEW
Ivana Vancurova, Mohammad M Uddin, Yue Zou, Ales Vancura
The rationale for developing histone deacetylase (HDAC) inhibitors (HDACi) as anticancer agents was based on their ability to induce apoptosis and cell cycle arrest in cancer cells. However, while HDACi have been remarkably effective in the treatment of hematological malignancies, clinical studies with HDACi as single agents in solid cancers have been disappointing. Recent studies have shown that, in addition to inducing apoptosis in cancer cells, class I HDACi induce IκB kinase (IKK)-dependent expression of proinflammatory chemokines, such as interleukin-8 (IL8; CXCL8), resulting in the increased proliferation of tumor cells, and limiting the effectiveness of HDACi in solid tumors...
December 9, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29233148/dna-repair-protein-ape1-is-involved-in-host-response-during-pneumococcal-meningitis-and-its-expression-can-be-modulated-by-vitamin-b6
#9
Leonam G Coutinho, Ana Helena Sales de Oliveira, Matthias Witwer, Stephen L Leib, Lucymara F Agnez-Lima
BACKGROUND: The production of reactive oxygen species (ROS) during pneumococcal meningitis (PM) leads to severe DNA damage in the neurons and is the major cause of cell death during infection. Hence, the use of antioxidants as adjuvant therapy has been investigated. Previous studies have demonstrated the possible participation of apurinic/apyrimidinic endonuclease (APE1) during PM. The aims of this study were to investigate the APE1 expression in the cortical and hippocampal tissues of infant Wistar rats infected with Streptococcus pneumoniae and its association with cell death and understand the role of vitamin B6 (vitB6) as a protective factor against cell death...
December 12, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29229673/lncrna-gas5-suppresses-ovarian-cancer-by-inducing-inflammasome-formation
#10
Jie Li, Chen Yang, Yinguang Li, Aiyue Chen, Li Li, Zeshan You
OBJECTIVE: Long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5) is involved in various kinds of cancer. However, the role of lncGAS5 in the development of ovarian cancer remains unclear. In the current study, we explored the cellular mechanism and clinical value of lncRNA GAS5 in ovarian cancer. METHODS: Quantitative real-time PCR was used to detect mRNA level of LncRNA GAS5 in 20 ovarian cancer tissues. The effect of lncRNA GAS5 on cell proliferation was performed using CCK-8 assay...
December 11, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29228766/the-effects-of-addition-of-coenzyme-q10-to-metformin-on-sirolimus-induced-diabetes-mellitus
#11
In O Sun, Long Jin, Jian Jin, Sun Woo Lim, Byung Ha Chung, Chul Woo Yang
Background/Aims: This study was performed to determine whether adding coenzyme Q10 (CoQ10) to metformin (MET) has a beneficial effect as a treatment for sirolimus (SRL)-induced diabetes mellitus (DM). Methods: DM was induced in rats by daily treatment with SRL (0.3 mg/kg, subcutaneous) for 28 days, and animals were treated with CoQ10 (20 mg/kg, oral) and MET (250 mg/kg, oral) alone or in combination for the latter 14 days of SRL treatment. The effects of CoQ10 and MET on SRL-induced DM were assessed with the intraperitoneal glucose tolerance test (IPGTT) and by determining plasma insulin concentration and the homeostatic model assessment of insulin resistance (HOMA-R) index...
December 13, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29228705/yap1-inhibition-radiosensitizes-triple-negative-breast-cancer-cells-by-targeting-the-dna-damage-response-and-cell-survival-pathways
#12
Daniel Andrade, Meghna Mehta, James Griffith, Janani Panneerselvam, Akhil Srivastava, Tae-Dong Kim, Ralf Janknecht, Terence Herman, Rajagopal Ramesh, Anupama Munshi
The Hippo pathway is an evolutionarily conserved signaling pathway that regulates proliferation and apoptosis to control organ size during developmental growth. Yes-associated protein 1 (YAP1), the terminal effector of the Hippo pathway, is a transcriptional co-activator and a potent growth promoter that has emerged as a critical oncogene. Overexpression of YAP1 has been implicated in promoting resistance to chemo-, radiation and targeted therapy in various cancers. However, the role of YAP1 in radioresistance in triple-negative breast cancer (TNBC) is currently unknown...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228685/eb1-phosphorylation-mediates-the-functions-of-ask1-in-pancreatic-cancer-development
#13
Siqi Gao, Youguang Luo, Xiaofan Wu, Yuanyuan Li, Yunqiang Zhou, Rui Lyu, Min Liu, Dengwen Li, Jun Zhou
Pancreatic cancer has a poor prognosis due to its rapid rate of metastasis and frequent late-stage diagnosis. An improved understanding of the molecular mechanisms underlying this disease is urgently needed to promote the development of improved diagnostic tools and more effective therapies. Apoptosis signal-regulating kinase 1 (ASK1) has been shown to be overexpressed in pancreatic cancer and to promote the proliferation of pancreatic cancer cells in a kinase activity-dependent manner. However, the molecular mechanisms by which ASK1 promotes cell proliferation remain to be elucidated...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228668/tsc-22-inhibits-csf-1r-function-and-induces-apoptosis-in-cervical-cancer
#14
Min-Ji Cho, Ji-Yeon Lee, Min-Gwan Shin, Hyun-Ji Kim, Yu-Joung Choi, Seung Bae Rho, Boh-Ram Kim, Ik Soon Jang, Seung-Hoon Lee
Colony stimulating factor 1 receptor (CSF-1R) regulates the monocyte/macrophage system, which is an essential component of cancer development. Therefore, CSF-1R might be an effective target for anti-cancer therapy. The overexpression of transforming growth factor (TGF)-β stimulated clone-22 (TSC-22) inhibits cancer cell proliferation and induces apoptosis, and TSC-22 is emerging as a key factor in tumorigenesis. In this study, we discovered CSF-1R as a new interacting partner of TSC-22 and identified its elevated expression in cervical cancer cells...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228614/dual-effects-of-radiation-bystander-signaling-in-urothelial-cancer-purinergic-activation-of-apoptosis-attenuates-survival-of-urothelial-cancer-and-normal-urothelial-cells
#15
Malgorzata A Bill, Kirtiman Srivastava, Conor Breen, Karl T Butterworth, Stephen J McMahon, Kevin M Prise, Karen D McCloskey
Radiation therapy (RT) delivers tumour kill, directly and often via bystander mechanisms. Bladder toxicity is a dose limiting constraint in pelvic RT, manifested as radiation cystitis and urinary symptoms. We aimed to investigate the impact of radiation-induced bystander signaling on normal/cancer urothelial cells. Human urothelial cancer cells T24, HT1376 and normal urothelial cells HUC, SV-HUC were used. Cells were irradiated and studied directly, or conditioned medium from irradiated cells (CM) was transferred to naïve, cells...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228610/targeting-polo-like-kinase-1-in-smarcb1-deleted-atypical-teratoid-rhabdoid-tumor
#16
Irina Alimova, Angela M Pierce, Peter Harris, Andrew Donson, Diane K Birks, Eric Prince, Ilango Balakrishnan, Nicholas K Foreman, Marcel Kool, Lindsey Hoffman, Sujatha Venkataraman, Rajeev Vibhakar
Atypical teratoid rhabdoid tumor (ATRT) is an aggressive and malignant pediatric brain tumor. Polo-like kinase 1 (PLK1) is highly expressed in many cancers and essential for mitosis. Overexpression of PLK1 promotes chromosome instability and aneuploidy by overriding the G2-M DNA damage and spindle checkpoints. Recent studies suggest that targeting PLK1 by small molecule inhibitors is a promising approach to tumor therapy. We investigated the effect of PLK1 inhibition in ATRT. Gene expression analysis showed that PLK1 was overexpressed in ATRT patient samples and tumor cell lines...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228593/proteasome-inhibitor-bortezomib-enhances-the-effect-of-standard-chemotherapy-in-small-cell-lung-cancer
#17
Sanaz Taromi, Florentine Lewens, Ruza Arsenic, Dagmar Sedding, Jörg Sänger, Almut Kunze, Markus Möbs, Joana Benecke, Helma Freitag, Friederike Christen, Daniel Kaemmerer, Amelie Lupp, Mareike Heilmann, Hedwig Lammert, Claus-Peter Schneider, Karen Richter, Michael Hummel, Britta Siegmund, Meike Burger, Franziska Briest, Patricia Grabowski
Small cell lung cancer (SCLC) is an aggressive cancer showing a very poor prognosis because of metastasis formation at an early stage and acquisition of chemoresistance. One key driver of chemoresistance is the transcription factor Forkhead box protein M1 (FOXM1) that regulates cell cycle proliferation, maintenance of genomic stability, DNA damage response, and cell differentiation in numerous tumor entities. In this study we investigated the role of FOXM1 in SCLC progression and analyzed the effect of FOXM1 inhibition using two proteasome inhibitors, bortezomib and siomycin A...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227548/resistance-of-oral-cancer-cells-to-5-ala-mediated-photodynamic-therapy
#18
Flávia Cristina Perillo Rosin, Marina Gabriela Teixeira, Cibele Pelissari, Luciana Corrêa
Photodynamic therapy (PDT) has been indicated for oral squamous cell carcinoma (OSCC) at early stages. Chemo and radio-resistance are frequently observed in OSCC, but it is unknown whether this tumor can develop resistance to PDT. It was investigated the process of acquiring resistance to multiple cycles of PDT by using OSCC cells. We also analyzed the expression of anti-apoptotic proteins and those related to Akt/mTOR pathway. Sub-lethal doses of PDT were applied, consisting of a constant concentration of 5-aminolevulinic acid (5-ALA) (1 mM, 4-hour incubation) and increasing irradiation dose with LED (from 5...
December 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29227537/ngal-gene-silencing-inhibits-proliferation-and-promotes-apoptosis-of-human-gastric-cancer-cells-an-in-vivo-and-in-vitro-study
#19
Ming-Yang Han, Jie-Wei Nie, Yuan-Yuan Li, Yuan-Zeng Zhu, Gang Wu
This study aims to explore effects of neutrophil gelatinase-associated lipocalin (NGAL) gene silencing on the proliferation and apoptosis of human gastric cancer MGC-803 and SGC-7901 cells. NGAL-siRNA was designed, synthesized and randomly divided into NGAL-siRNA and control-siRNA groups. Gastric cancer cells MGC-803 and SGC-7901 were grouped into blank, NGAL-OE, and control-OE groups. Expression of NGAL and apoptosis-related proteins were detected by qRT-PCR and Western blotting. Cell cycle and apoptosis were tested by flow cytometry, and cell proliferation by water soluble tetrazolium-1 (WST-1) assay...
December 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29227477/the-deubiquitinating-enzyme-tnfaip3-mediates-inactivation-of-hepatic-ask1-and-ameliorates-nonalcoholic-steatohepatitis
#20
Peng Zhang, Pi-Xiao Wang, Ling-Ping Zhao, Xin Zhang, Yan-Xiao Ji, Xiao-Jing Zhang, Chun Fang, Yue-Xin Lu, Xia Yang, Mao-Mao Gao, Yan Zhang, Song Tian, Xue-Yong Zhu, Jun Gong, Xin-Liang Ma, Feng Li, Zhihua Wang, Zan Huang, Zhi-Gang She, Hongliang Li
Activation of apoptosis signal-regulating kinase 1 (ASK1) in hepatocytes is a key process in the progression of nonalcoholic steatohepatitis (NASH) and a promising target for treatment of the condition. However, the mechanism underlying ASK1 activation is still unclear, and thus the endogenous regulators of this kinase remain open to be exploited as potential therapeutic targets. In screening for proteins that interact with ASK1 in the context of NASH, we identified the deubiquitinase tumor necrosis factor alpha-induced protein 3 (TNFAIP3) as a key endogenous suppressor of ASK1 activation, and we found that TNFAIP3 directly interacts with and deubiquitinates ASK1 in hepatocytes...
December 11, 2017: Nature Medicine
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