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BCL2 inhibition

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https://www.readbyqxmd.com/read/29348885/drug-resistance-in-doxorubicin-resistant-fl5-12-hematopoietic-cells-elevated-mdr1-drug-efflux-and-side-population-positive-and-decreased-bcl2-family-member-expression
#1
Linda S Steelman, Steve L Abrams, Peter Ruvolo, Vivian Ruvolo, Lucio Cocco, Stefano Ratti, Alberto M Martelli, Luca M Neri, Saverio Candido, Massimo Libra, James A McCubrey
Chemotherapeutic drug treatment can result in the emergence of drug-resistant cells. By culturing an interleukin-3 (IL-3)-dependent cell line, FL5.12 cells in the presence of the chemotherapeutic drug doxorubicin, we isolated FL/Doxo cells which are multi-drug resistant. Increased levels of drug efflux were detected in FL/Doxo cells which could be inhibited by the MDR1 inhibitor verapamil but not by the MRP1 inhibitor MK571. The effects of TP53 and MEK1 were examined by infection of FL/Doxo cells with retroviruses encoding either a dominant negative TP-53 gene (FL/Doxo+ TP53 (DN) or a constitutively-activated MEK-1 gene (FL/Doxo + MEK1 (CA)...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29345419/targeting-bcl2-gene-promoter-g-quadruplex-with-a-new-class-of-furopyridazinone-based-molecules
#2
Jussara Amato, Alessia Pagano, Domenica Capasso, Sonia Di Gaetano, Mariateresa Giustiniano, Ettore Novellino, Antonio Randazzo, Bruno Pagano
Targeting of G-quadruplex-forming DNA in BCL2 gene promoter to inhibit the expression of anti-apoptotic Bcl-2 protein represents an attractive opportunity in cancer treatment. So far, efforts made in the discovery of molecules able to target BCL2 G-quadruplex mainly succeeded in the identification of ligands with poor drug-like properties. Here, a small series of furo[2,3-d]pyridazin-4(5H)-one derivatives were evaluated as a new class of drug-like G-quadruplex-targeting compounds. Biophysical studies showed that two derivatives could effectively bind to BCL2 G-quadruplex with good selectivity...
January 18, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29344647/autophagy-regulates-the-degeneration-of-the-auditory-cortex-through-the-ampk-mtor-ulk1-signaling-pathway
#3
Jie Yuan, Xueyan Zhao, Yujuan Hu, Haiying Sun, Guoqing Gong, Xiang Huang, Xubo Chen, Mingyu Xia, Chen Sun, Qilin Huang, Yu Sun, Wen Kong, Weijia Kong
Presbycusis is the most common sensory impairment associated with aging; however, the underlying molecular mechanism remains unclear. Autophagy has been demonstrated to serve a key role in diverse diseases; however, no studies have examined its function in central presbycusis. The aim of the present study was to investigate the changes of autophagy in the physiological processes of the auditory cortex and its role in the degeneration of the auditory cortex, as well as the related mechanisms using naturally aging rats and a D‑galactose (D‑gal)‑induced mimetic rat model of aging...
January 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29344281/keratin17-promotes-tumor-growth-and-is-associated-with-poor-prognosis-in-gastric-cancer
#4
Hao Hu, Dan-Hua Xu, Xiao-Xu Huang, Chun-Chao Zhu, Jia Xu, Zi-Zhen Zhang, Gang Zhao
Krt17 is a 48kDa protein member of keratin family. Previous literatures have demonstrated Krt17 may play a promotive role in the progression of various malignancies. However, the exact function of Krt17 in the carcinogenesis and the progression of gastric cancer (GC) remains unknown. In the present study, the expression of Krt17 in 20 fresh GC and matched normal tissues were detected and Krt17 was found to be significantly increased in GC tissues compared to normal tissues. And then the immunochemistry was performed to investigate the Krt17 expression in 569 GC tissue specimens, we found that the expression of Krt17 was remarkably positively correlated with the tumor size (P < 0...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29344203/mucin-1-promotes-radioresistance-in-hepatocellular-carcinoma-cells-through-activation-of-jak2-stat3-signaling
#5
Feng-Tao Yi, Qi-Ping Lu
Mucin 1 (MUC1) is aberrantly overexpressed in numerous human cancer types, including hepatocellular carcinoma (HCC) and contributes to chemoresistance of tumor cells. The aim of the present study was to evaluate the possible implication of MUC1 in radioresistance of HCC cells and the underlying mechanisms. It was demonstrated that MUC1 was significantly upregulated in HCC cells following irradiation exposure, which was coupled with increased phosphorylation of signal transducer and activator of transcription 3 (STAT3)...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29330143/breast-cancer-targeting-through-inhibition-of-the-endoplasmic-reticulum-based-apoptosis-regulator-nrh-bcl2l10
#6
Adrien Nougarede, Nikolay Popgeorgiev, Loay Kassem, Soleilmane Omarjee, Stephane Borel, Ivan Mikaelian, Jonathan Lopez, Rudy Gadet, Olivier Marcillat, Isabelle Treilleux, Bruno O Villoutreix, Ruth Rimokh, Germain Gillet
Drug resistance and metastatic relapse remain a top challenge in breast cancer treatment. In this study, we present preclinical evidence for a strategy to eradicate advanced breast cancers by targeting the BCL2 homolog Nrh/BCL2L10, which we discovered to be overexpressed in >45% of a large cohort of breast invasive carcinomas. Nrh expression in these tumors correlated with reduced metastasis-free survival and we determined it to be an independent marker of poor prognosis. Nrh protein localized to the endoplasmic reticulum (ER)...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29324385/ameliorative-effects-of-selenium-on-arsenic-induced-cytotoxicity-in-pc12%C3%A2-cells-via-modulating-autophagy-apoptosis
#7
Md Mostafizur Rahman, Rachael A Uson-Lopez, Md Tajuddin Sikder, Gongxun Tan, Toshiyuki Hosokawa, Takeshi Saito, Masaaki Kurasaki
Arsenic is well known toxicant responsible for human diseases including cancers. On the other hand, selenium is an essential trace element with significant chemopreventive effects, anticancer potentials and antioxidant properties. Although previous studies have reported antagonism/synergism between arsenic and selenium in biological systems, the biomolecular mechanism/s is still inconclusive. Therefore, to elucidate the molecular phenomena in cellular level, we hypothesized that co-exposure of selenium with arsenic may have suppressive effects on arsenic-induced cytotoxicity...
December 28, 2017: Chemosphere
https://www.readbyqxmd.com/read/29323715/alleviation-of-palmitic-acid-induced-endoplasmic-reticulum-stress-by-augmenter-of-liver-regeneration-through-ip3r-controlled-ca2-release
#8
Wei-Chun Xiao, Zhang Jing, Si-Li Chen, Yi-Jun Shi, Fan Xiao, Wei An
The aberrant release of Ca2+ from the endoplasmic reticulum (ER) contributes to the onset of ER stress, which is closely related to the pathogenesis of non-alcoholic fatty liver disease. We previously reported that augmenter of liver regeneration (ALR) alleviates ER stress and protects hepatocytes from lipotoxicity. However, the link between ALR protection and the suppression of ER stress remains unclear. In this study, we investigated whether the protection against liver steatosis afforded by ALR is related to its inhibition of calcium overflow from the ER to the mitochondria...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29304412/developmental-toxicity-and-potential-mechanisms-of-pyraoxystrobin-to-zebrafish-danio-rerio
#9
Hui Li, Song Yu, Fangjie Cao, Chengju Wang, Mingqi Zheng, Xuefeng Li, Lihong Qiu
As a newly developed, highly efficient strobilurin fungicide, pyraoxystrobin has been reported to be highly toxic to some aquatic organisms. However, the toxicity of pyraoxystrobin to different life stages of fish and the potential underlying mechanisms are still unknown. Hence, in the present study, the acute toxicity of pyraoxystrobin to different life stages of zebrafish (embryo, larva, and adult) was assessed. The developmental toxicity of pyraoxystrobin to zebrafish embryos and its effects on gene transcription in the embryo were also investigated...
January 2, 2018: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29295729/mir-206-inhibits-cell-proliferation-migration-and-invasion-by-targeting-bag3-in-human-cervical-cancer
#10
Yingying Wang, Yongjie Tian
miR-206 and bcl2-associated athanogene 3 (BAG3) have been suggested as important regulators in various cancer types. However, the biological role of miR-206 and BAG3 in cervical cancer (CC) remains unclear. Here, we investigated the expressions and mechanisms of miR-206 and BAG3 in cervical cancer using in vitro and in vivo assays. In the present study, miR-206 expression was expressed at a lower level in CC tissues and cells than adjacent normal tissues and NEEC cells. By contrast, BAG3 mRNA and protein were expressed at higher levels in CC tissues and cells...
January 2, 2018: Oncology Research
https://www.readbyqxmd.com/read/29295692/socs6-functions-as-a-tumor-suppressor-by-inducing-apoptosis-and-inhibiting-angiogenesis-in-human-prostate-cancer
#11
Dongbo Yuan, Wei Wang, Jiaming Su, Yongqiang Zhang, Boshi Luan, Haofu Rao, Tianfei Cheng, Wei Zhang, Shiwei Xiao, Mingsheng Zhang, Fu-Neng Jiang, Zhaolin Sun, Zhenyu Jia, Wei-De Zhong, Jianguo Zhu
Our previous studies revealed that the downregulation of Suppressor of cytokine signaling 6 (SOCS6) was correlated with malignant progression of human prostate cancer (PCa). In the current study, we aimed to investigate the tumor suppressive roles of SOCS6 and the underlying mechanisms in PCa. SOCS6 expression in PCa and non-cancerous prostate tissues were compared by immunohistochemistry. Statistical associations of SOCS6 expression with various clinicopathological features and patients' prognosis were evaluated...
January 1, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29285137/inhibition-of-chemotherapy-induced-apoptosis-of-testicular-cells-by-squid-ink-polysaccharide
#12
Yi-Peng Gu, Xiao-Mei Yang, Zhen-Hua Duan, Ping Luo, Jiang-Hua Shang, Wei Xiao, Ye-Xing Tao, Da-Yan Zhang, Yun-Bo Zhang, Hua-Zhong Liu
The aim of this study was to determine the mechanisms driving the protective effects of squid ink polysaccharide (SIP) against cyclophosphamide (CP)-induced testicular damage, focusing on germ cells. In the testes of mice exposed to CP and/or SIP, the present study examined the levels of reactive oxygen species (ROS) and malondialdehyde, activity of superoxide dismutase levels, protein expression levels of B-cell lymphoma 2 (Bcl2), Bcl2-associated X protein (Bax), and total Caspase 3, activation of p-p38 and p-Akt proteins, and tissue morphology...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29281558/long-non-coding-rna-cebpa-as1-correlates-with-poor-prognosis-and-promotes-tumorigenesis-via-cebpa-bcl2-in-oral-squamous-cell-carcinoma
#13
Yan Guo, Yuji Ma, Xuanhao Hu, Rongbo Song, Li Zhu, Ming Zhong
Oral squamous cell carcinoma (OSCC) is one of the most aggressive and lethal malignancies affecting the head and neck region with a general 5-year survival rate about 50%. Long non-coding RNAs (lncRNAs) are believed to participate in diverse biological processes and are emerging as convenient and minimally invasive diagnostic/prognostic/therapeutic markers. The aim of this study was to explore CEBPA-AS1 role and mechanism in OSCC tumorigenesis. In this study, CEBPA-AS1 localized in the cytoplasm and the peri-nuclear cellular compartment functioning as a potential oncogene up-regulated in OSCC was correlated with poor differentiation, lymph node metastasis and high clinical stage, which made it considered to be a prognostic biomarker...
December 27, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29280516/suppression-of-stat3-nh2-terminal-domain-chemosensitizes-medulloblastoma-cells-by-activation-of-protein-inhibitor-of-activated-stat3-via-de-repression-by-microrna-21
#14
Sutapa Ray, Don W Coulter, Shawn D Gray, Jason A Sughroue, Shrabasti Roychoudhury, Erin M McIntyre, Nagendra K Chaturvedi, Kishor K Bhakat, Shantaram S Joshi, Timothy R McGuire, John G Sharp
Medulloblastoma (MB) is a malignant pediatric brain tumor with poor prognosis. Signal transducers and activators of transcription-3 (STAT3) is constitutively activated in MB where it functions as an oncoprotein, mediating cancer progression and metastasis. Here, we have delineated the functional role of activated STAT3 in MB, by using a cell permeable STAT3-NH2 terminal domain inhibitor (S3-NTDi) that specifically perturbs the structure/function of STAT3. We have implemented several biochemical experiments using human MB tumor microarray (TMA) and pediatric MB cell lines, derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/SHH tumors...
December 27, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29280311/fluorination-enhances-serum-stability-of-bioreducible-poly-amido-amine-polyplexes-and-enables-efficient-intravenous-sirna-delivery
#15
Gang Chen, Kaikai Wang, Yixin Wang, Pengkai Wu, Minjie Sun, David Oupický
The use of small interfering RNA (siRNA) in cancer treatment has been limited by the lack of effective systemic delivery methods. Although synthetic polycations have been widely explored in siRNA delivery, polycation/siRNA polyplexes often suffer from insufficient stability in vivo. Here, rationally designed siRNA delivery systems that meet the requirements for systemic siRNA delivery to distant tumors are reported. The hypothesis that modular design of delivery systems based on poly(amido amine)s that combine fluorination for systemic stability with bioreducibility for easy intracellular siRNA release, and PEGylation for improved safety and colloidal stability will overcome problems with contradicting siRNA delivery demands is tested...
December 27, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29274969/effect-of-17%C3%AE-estradiol-on-milk-production-hormone-secretion-and-mammary-gland-gene-expression-in-dairy-cows
#16
J J Tong, I M Thompson, X Zhao, P Lacasse
Estradiol inhibits milk production in dairy cows. The present study evaluated the effect of 17β-estradiol (E2) injections on prolactin (PRL) secretion and the mammary gland response to this hormone. Eight mid-lactation cows were used in a crossover design. During each experimental period, the cows were injected daily with either E2 (2.5 mg) or soy oil (2.5 mL; control) for 7 d. For each period, blood and milk samples were collected from d -4 to 14 (relative to the first injection) to measure PRL, insulin-like growth factor-1, and cortisol concentrations...
December 20, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29259166/inhibition-of-autophagy-delays-motoneuron-degeneration-and-extends-lifespan-in-a-mouse-model-of-spinal-muscular-atrophy
#17
Antonio Piras, Lorenzo Schiaffino, Marina Boido, Valeria Valsecchi, Michela Guglielmotto, Elena De Amicis, Julien Puyal, Ana Garcera, Elena Tamagno, Rosa M Soler, Alessandro Vercelli
Spinal muscular atrophy (SMA) is a recessive autosomal neuromuscular disease, due to homozygous mutations or deletions in the telomeric survival motoneuron gene 1 (SMN1). SMA is characterized by motor impairment, muscle atrophy, and premature death following motor neuron (MN) degeneration. Emerging evidence suggests that dysregulation of autophagy contributes to MN degeneration. We here investigated the role of autophagy in the SMNdelta7 mouse model of SMA II (intermediate form of the disease) which leads to motor impairment by postnatal day 5 (P5) and to death by P13...
December 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29259008/cxcr4-promotes-neuroblastoma-growth-and-therapeutic-resistance-through-mir-15a-16-1-mediated-erk-and-bcl2-cyclin-d1-pathways
#18
Shiri Klein, Michal Abraham, Baruch Bulvik, Elia Dery, Ido D Weiss, Neta Barashi, Rinat Abramovitch, Hanna Wald, Yaniv Harel, Devorah Olam, Lola Weiss, Katia Beider, Orly Eizenberg, Ori Wald, Eithan Galun, Yaron Pereg, Amnon Peled
CXCR4 expression in neuroblastoma (NB) tumors correlates with disease severity. In this study, we describe mechanisms by which CXCR4 signaling controls NB tumor growth and response to therapy. We found that overexpression of CXCR4 or stimulation with CXCL12 supports NB tumorigenesis. Moreover, CXCR4 inhibition with the high affinity CXCR4 antagonist, BL-8040 prevented tumor growth and reduced survival of tumor cells. These effects were mediated by the upregulation of miR-15a/16-1, which resulted in downregulation of their target genes BCL-2 and cyclin D1, as well as inhibition of ERK...
December 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/29258619/effects-of-low-intensity-pulsed-ultrasound-lipus-pretreated-human-amnion-derived-mesenchymal-stem-cell-had-msc-transplantation-on-primary-ovarian-insufficiency-in-rats
#19
Li Ling, Xiushan Feng, Tianqin Wei, Yan Wang, Yaping Wang, Wenqian Zhang, Lianli He, Ziling Wang, Qianru Zeng, Zhengai Xiong
BACKGROUND: Human amnion-derived mesenchymal stem cells (hAD-MSCs) have the features of mesenchymal stem cells (MSCs). Low-intensity pulsed ultrasound (LIPUS) can promote the expression of various growth factors and anti-inflammatory molecules that are necessary to keep the follicle growing and to reduce granulosa cell (GC) apoptosis in the ovary. This study aims to explore the effects of LIPUS-pretreated hAD-MSC transplantation on chemotherapy-induced primary ovarian insufficiency (POI) in rats...
December 19, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29251322/mir-29a-inhibits-human-retinoblastoma-progression-by-targeting-stat3
#20
Shu Liu, Xiaomeng Zhang, Chunmei Hu, Yingxue Wang, Chunling Xu
Retinoblastoma (RB) is the most common malignancy that occurs during childhood. Growing evidence supports a crucial role for microRNAs (miRNAs) in regulating the initiation and progression of RB. Aberrant expression of microRNA‑29a (miR‑29a) has been found in many types of cancers, but not including RB. Therefore, the aims of the present study were to evaluate the regulatory role and underlying mechanism of miR‑29a in human RB. In the present study, we found that miR‑29a expression was significantly downregulated in RB tissues and cell lines...
February 2018: Oncology Reports
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