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Apoptosis therapy

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https://www.readbyqxmd.com/read/29054095/ginkgolide-b-and-bilobalide-ameliorate-neural-cell-apoptosis-in-%C3%AE-synuclein-aggregates
#1
Jun Hua, Nuo Yin, Beibei Yang, Ji Zhang, Jianhua Ding, Yi Fan, Gang Hu
The accumulation of aggregated forms of the α-Synuclein (α-Syn) is associated with the pathogenesis of Parkinson's disease (PD), a chronic progressive neurodegenerative disorder. Extensive evidences have shown the promising effects of Ginkgo biloba consumption on motor activity after PD. However, the mechanisms underline the α-Syn-induced cell damage and whether ginkgolides exert neuroprotection against this injury are unclear. Here we showed that aggregated recombinant human α-Syn, but not α-Syn monomers, triggered cell injury in cultured human neuroblastoma cell line SH-SY5Y in an apoptosis way by using flow cytometry and western blot assay...
October 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29053680/evaluating-in-vitro-dna-damage-using-comet-assay
#2
Yanxin Lu, Yang Liu, Chunzhang Yang
DNA damage is a common phenomenon for each cell during its lifespan, and is defined as an alteration of the chemical structure of genomic DNA. Cancer therapies, such as radio- and chemotherapy, introduce enormous amount of additional DNA damage, leading to cell cycle arrest and apoptosis to limit cancer progression. Quantitative assessment of DNA damage during experimental cancer therapy is a key step to justify the effectiveness of a genotoxic agent. In this study, we focus on a single cell electrophoresis assay, also known as the comet assay, which can quantify single and double-strand DNA breaks in vitro...
October 11, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053537/thermal-ultra-short-photodynamic-therapy-heating-fibroblasts-during-sub-30-minute-incubation-of-5-aminolevulinic-acid-increases-photodynamic-therapy-induced-cell-death
#3
Eugene Koo, Evan Austin, Andrew Mamalis, Jared Jagdeo
BACKGROUND: Actinic keratoses (AKs) prevalence was estimated at 39.5 million Americans in 2004, and the cost to treat AKs that year was approximately 1 billion dollars. Photodynamic therapy (PDT) is an FDA-approved therapy for the treatment of AK. Recent studies have focused on reducing PDT treatment time while maintaining efficacy. OBJECTIVE: To investigate the use of thermal modulation to improve the efficacy of ultra short aminolevulinic acid (ALA) incubation PDT...
October 19, 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/29053471/pegylated-anticancer-carbon-nanotubes-complex-targeting-mitochondria-of-lung-cancer-cells
#4
Sang-Woo Kim, Yeon Kyung Lee, Jong Yeon Lee, Jeong Hee Hong, Dongwoo Khang
Although activating apoptosis in cancer cells by targeting the mitochondria is an effective strategy for cancer therapy, insufficient targeting of the mitochondria in cancer cells restricts the availability in clinical treatment. Here, we report on a polyethylene glycol-coated carbon nanotube (CNT)-ABT737 nanodrug that improves the mitochondrial targeting of lung cancer cells. The polyethylene glycol-coated CNT-ABT737 nanodrug internalized into the early endosomes via macropinocytosis and clathrin-mediated endocytosis in advance of early endosomal escape and delivered into the mitochondria...
October 20, 2017: Nanotechnology
https://www.readbyqxmd.com/read/29053168/fl-926-16-a-novel-bioavailable-carnosinase-resistant-carnosine-derivative-prevents-onset-and-stops-progression-of-diabetic-nephropathy-in-db-db-mice
#5
Carla Iacobini, Stefano Menini, Claudia Blasetti Fantauzzi, Carlo M Pesce, Andrea Giaccari, Enrica Salomone, Annunziata Lapolla, Marica Orioli, Giancarlo Aldini, Giuseppe Pugliese
BACKGROUND AND PURPOSE: The advanced glycation endproducts (AGEs) participate in the pathogenesis of diabetic nephropathy (DN) by promoting renal inflammation and injury. L-carnosine acts as a quencher of the AGE precursors reactive carbonyl species (RCS), but it is rapidly inactivated by carnosinase. This study evaluated the effect of FL-926-16, a carnosinase-resistant and bioavailable carnosine derivative, on the onset and progression of DN in db/db mice. EXPERIMENTAL APPROACH: Adult male db/db mice and coeval db/m controls were left untreated or treated with FL-926-16 (30 mg·kg(-1) body weight) from week 6 to 20 (prevention protocol) or from week 20 to 34 (regression protocol)...
October 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29052798/curcumin-pretreatment-prevents-hydrogen-peroxide-induced-oxidative-stress-through-enhanced-mitochondrial-function-and-deactivation-of-akt-erk-signaling-pathways-in-rat-bone-marrow-mesenchymal-stem-cells
#6
Xujie Wang, Jianxin Gao, Yunchuan Wang, Bin Zhao, Yijie Zhang, Fu Han, Zhao Zheng, Dahai Hu
Bone marrow mesenchymal stem cells (BMSCs)-based therapy has emerged as a desirable modality for the treatment of tissue injury with promising therapeutic effects; however, low survival rate of transplanted cells due to harsh microenvironment with hypoxia and oxidative stress results in hampered therapeutic benefits of this therapy. Curcumin, a natural bioactive product, is a dietary component which has gained increasing attention owing to its beneficial health properties. Here, we reported the protective effects of curcumin pretreatment on BMSCs injury induced by hydrogen peroxide (H2O2), which was used as ROS source of oxidative stress in vitro...
October 20, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29052449/resveratrol-in-management-of-bone-and-spinal-cancers
#7
Gang Chen, Hong Xia, Zhi-Guo Zhang, Hai-Liang Yu
Bone cancer is a malignant primary tumour of the bone with different typing, such as, osteosarcoma, chondrosarcoma, Ewing's sarcoma and fibrosarcoma. Despite the clinical efficacy of conventional therapies of bone cancer, most patients eventually relapse and the disease remains incurable. Therefore, new therapeutic strategies are needed to improve patient outcome. In this review article, we have discussed the role of resveratrol in preventing bone and spinal cancers and therapeutics. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural polyphenol, which has been widely reported as an anticancer molecule...
October 20, 2017: Natural Product Research
https://www.readbyqxmd.com/read/29051323/epithelial-to-mesenchymal-transition-antagonizes-response-to-targeted-therapies-in-lung-cancer-by-suppressing-bim
#8
Anthony C Faber, Kyung-A Song, Matthew J Niederst, Timothy L Lochmann, Aaron N Hata, Hidenori Kitai, Jungoh Ham, Konstantinos V Floros, Mark A Hicks, Haichuan Hu, Hillary E Mulvey, Yotam Drier, Daniel A R Heisey, Mark T Hughes, Neha U Patel, Elizabeth Lockerman, Angel R Garcia, Shawn Gillepsie, Hannah L Archibald, Maria Gomez-Caraballo, Tara J Nulton, Brad Windle, Zofia Piotrowska, Sinem E Sahingur, Shirley M Taylor, Mikhail G Dozmorov, Lecia V Sequist, Bradley E Bernstein, Hiromichi Ebi, Jeffrey A Engelman
PURPOSE: Epithelial-to-mesenchymal transition (EMT) confers resistance to a number of targeted therapies and chemotherapies. However, it has been unclear why EMT promotes resistance, thereby impairing progress to overcome it. EXPERIMENTAL DESIGN: We have developed several models of EMT-mediated resistance to EGFR inhibitors (EGFRi) in EGFR mutant lung cancers to evaluate a novel mechanism of EMT-mediated resistance. Results: We observed that mesenchymal EGFR mutant lung cancers are resistant to EGFRi-induced apoptosis via insufficient expression of BIM, preventing cell death despite potent suppression of oncogenic signaling following EGFRi treatment...
October 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29051320/combinatorial-treatment-with-mtor-inhibitors-and-streptozotocin-leads-to-synergistic-in-vitro-and-in-vivo-antitumor-effects-in-insulinoma-cells
#9
Julien Bollard, Céline Patte, Patrick Massoma, Isabelle Goddard, Nicolas Gadot, Noura Benslama, Valérie Hervieu, Carole Ferraro-Peyret, Martine Cordier-Bussat, Jean-Yves Scoazec, Colette Roche, Thomas Walter, Cécile Vercherat
Streptozotocin (STZ)-based chemotherapy is the first-line chemotherapy recommended for advanced pancreatic neuroendocrine tumors (pNETs), while targeted therapies, including mTOR inhibitors, are available in second-line treatment. Unfortunately objective response rates to both treatments are limited. Since mTOR pathway activation, commonly observed in pNETs, has been reported as one of the major mechanisms accounting for chemoresistance, we investigated the potential benefit of mTOR inhibition combined with STZ treatment in a subset of pNETs, namely insulinomas...
October 19, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29050982/pharmacological-inhibition-of-dusp6-suppresses-gastric-cancer-growth-and-metastasis-and-overcomes-cisplatin-resistance
#10
Qi-Nian Wu, Yi-Fu Liao, Yun-Xin Lu, Yun Wang, Jia-Huan Lu, Zhao-Lei Zeng, Qi-Tao Huang, Hui Sheng, Jing-Ping Yun, Dan Xie, Huai-Qiang Ju, Rui-Hua Xu
Gastric cancer (GC) is the second cause of cancer-related death. Cisplatin (CDDP) is widely used as the standard GC treatment, but relapse and metastasis are common because of intrinsic or acquired drug resistance. The mitogen-activated protein kinase phosphatases (MAPK)-extracellular signal regulated kinases (ERK) pathway contributes to GC progression and drug resistance, but targeting the MAPK-ERK pathway is challenging in GC therapy. Here, we demonstrated that dual-specificity phosphatases 6 (DUSP6) was overexpressed in GC and predicted poor overall survival and progression-free survival...
October 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29050671/gambogic-acid-improves-non-small-cell-lung-cancer-progression-by-inhibition-of-mtor-signaling-pathway
#11
Teng Zhao, Hong-Jian Wang, Wen-Wen Zhao, Yi-Ling Sun, Li-Kuan Hu
Gambogic acid (GA) has been shown to inhibit cancer cell proliferation, induce apoptosis, and enhance reactive oxygen species accumulation. However, whether GA could improve multidrug resistance through modulating autophagy has never been explored. We demonstrated that the combination of GA and cisplatin (CDDP) resulted in a stronger growth inhibition effect on A549 and NCI-H460 cells using the MTT assay. Furthermore, treatment with GA significantly increased autophagy in these cells. More importantly, GA-induced cell death could be largely abolished by 3-methyladenine (3-MA) or chloroquine (CQ) treatment, suggesting that GA-induced cell death was dependent on autophagy...
November 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/29050400/metformin-reverses-trap1-mutation-associated-alterations-in-mitochondrial-function-in-parkinson-s-disease
#12
Julia C Fitzgerald, Alexander Zimprich, Daniel A Carvajal Berrio, Kevin M Schindler, Brigitte Maurer, Claudia Schulte, Christine Bus, Anne-Kathrin Hauser, Manuela Kübler, Rahel Lewin, Dheeraj Reddy Bobbili, Lisa M Schwarz, Evangelia Vartholomaiou, Kathrin Brockmann, Richard Wüst, Johannes Madlung, Alfred Nordheim, Olaf Riess, L Miguel Martins, Enrico Glaab, Patrick May, Katja Schenke-Layland, Didier Picard, Manu Sharma, Thomas Gasser, Rejko Krüger
The mitochondrial proteins TRAP1 and HTRA2 have previously been shown to be phosphorylated in the presence of the Parkinson's disease kinase PINK1 but the downstream signalling is unknown. HTRA2 and PINK1 loss of function causes parkinsonism in humans and animals. Here, we identified TRAP1 as an interactor of HTRA2 using an unbiased mass spectrometry approach. In our human cell models, TRAP1 overexpression is protective, rescuing HTRA2 and PINK1-associated mitochondrial dysfunction and suggesting that TRAP1 acts downstream of HTRA2 and PINK1...
September 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29050323/histone-deacetylase-inhibitor-thailandepsin-a-activates-notch-signaling-and-suppresses-neuroendocrine-cancer-cell-growth-in-vivo
#13
Samuel Jang, Andrew Janssen, Zviadi Aburjania, Matthew B Robers, April Harrison, Ajitha Dammalapati, Yi-Qiang Cheng, Herbert Chen, Renata Jaskula-Sztul
Novel therapies for neuroendocrine (NE) cancers are desperately needed as they frequently present as metastatic disease and cause debilitating symptoms by secreting excessive hormones. Induction of Notch isoforms has a tumor suppressive effect in NE cancer cell lines, and we have observed that histone deacetylase inhibitors (HDACi) potently activate Notch. In this study, we describe the potential for Burkholderia thailandensis-derived class I HDACi thailandepsin A (TDP-A) as a Notch activator and therapeutic agent against NE cancer...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050292/foxk1-facilitates-cell-proliferation-through-regulating-the-expression-of-p21-and-promotes-metastasis-in-ovarian-cancer
#14
Li Li, Miao Gong, Yu Zhao, Xiujun Zhao, Quanhai Li
Ovarian cancer is one of the most common cancer in the world. FOX family plays essential function in multiple cancers. In our work, FOXK1 was found to up-regulate in ovarian cancer tissue samples and cell lines; moreover, the expression of FOXK1 was correlated with tumor size, metastasis and poorly prognosis. To evaluate the function of FOXK1 in ovarian cancer, we performed colony formation analysis, CCK-8 assay and cell cycle analysis to determine the effect of FOXK1 on cell proliferation and cell cycle. We found that FOXK1 obviously improved the ability of cell proliferation through promoting cell cycle...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050241/combination-treatment-with-rucaparib-rubraca-and-mdm2-inhibitors-nutlin-3-and-rg7388-has-synergistic-and-dose-reduction-potential-in-ovarian-cancer
#15
Maryam Zanjirband, Nicola Curtin, Richard J Edmondson, John Lunec
Ovarian cancer is the seventh most common cancer worldwide for females and the most lethal of all gynecological malignancies. The treatment of ovarian cancer remains a challenge in spite of advances in debulking surgery and changes in both chemotherapy schedules and routes of administration. Cancer treatment has recently been improving with the introduction of targeted therapies to achieve greater specificity and less cytotoxicity. Both PARP inhibitors and MDM2-p53 binding antagonists are targeted therapeutic agents entered into clinical trials...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050003/cantharidin-inhibits-the-growth-of-triple-negative-breast-cancer-cells-by-suppressing-autophagy-and-inducing-apoptosis-in-vitro-and-in-vivo
#16
Hong-Chang Li, Zhi-Hua Xia, Ya-Feng Chen, Fan Yang, Wen Feng, Han Cai, Yi Mei, Yi-Ming Jiang, Ke Xu, Dian-Xu Feng
BACKGROUND/AIMS: Cantharidin, a type of terpenoid secreted by the blister beetle Mylabris phalerata (Pallas), has attracted great attention in cancer therapy because of its potential anti-cancer activities. Here, we report the effects on apoptosis and autophagy in human triple-negative breast cancer (TNBC) cell lines after treatment with cantharidin and attempt to elucidate the underlying mechanisms. METHODS: MDA-MB-231 and MDA-MB-468 cells were treated with cantharidin and cell proliferation was examined using CCK-8 and clone formation assays...
October 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29049732/iron-chelating-drugs-enhance-cone-photoreceptor-survival-in-a-mouse-model-of-retinitis-pigmentosa
#17
Ke Wang, Bo Peng, Jia Xiao, Orly Weinreb, Moussa B H Youdim, Bin Lin
Purpose: Retinitis pigmentosa (RP) is a group of hereditary retinal degeneration in which mutations commonly result in the initial phase of rod cell death followed by gradual cone cell death. The mechanisms by which the mutations lead to photoreceptor cell death in RP have not been clearly elucidated. There is currently no effective treatment for RP. The purpose of this work was to explore iron chelation therapy for improving cone survival and function in the rd10 mouse model of RP. Methods: Two iron-chelating drugs, 5-(4-(2-hydroxyethyl) piperazin-1-yl (methyl)-8-hydroxyquinoline (VK28) and its chimeric derivative 5-(N-methyl-N-propargyaminomethyl)-quinoline-8-oldihydrochloride (VAR10303), were injected intraperitoneally to rd10 mice every other day starting from postnatal day 14...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29049036/histone-deacetylase-inhibitor-bg45-mediated-ho-1-expression-induces-apoptosis-of-multiple-myeloma-cells-by-the-jak2-stat3-pathway
#18
Sishi Tang, Bingqing Cheng, Nana Zhe, Dan Ma, Jibing Xu, Xinyao Li, Yongling Guo, Weibing Wu, Jishi Wang
Multiple myeloma (MM) is a hematological malignancy that is characterized by the clonal expansion of plasma cells in the bone marrow. Histone deacetylases (HDACs) represent a new type of molecular targeted therapy for different types of cancers and promising targets for myeloma therapy. We showed that HDAC3 mRNA and protein levels of CD138 mononuclear cells from MM patients were higher than those in healthy donors. Therefore, we investigated the effects of a novel class I HDAC inhibitor BG45 on MM cells in vitro...
October 18, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29048680/mir%C3%A2-146b%C3%A2-5p-suppresses-glioblastoma-cell-resistance-to-temozolomide-through-targeting-traf6
#19
Zhongrun Qian, Sunhai Zhou, Zhiyi Zhou, Xi Yang, Shuanlin Que, Jin Lan, Yongming Qiu, Yingying Lin
Temozolomide (TMZ), as a kind of alkylating agent, is widely utilized for the treatment of glioblastoma (GBM). However, temozolomide resistance (TR) often develops quickly and results in tumor recurrence and poor outcome. Recent advances have demonstrated that miRNAs exert critical roles in chemoresistance. Downregulation of miR‑146b‑5p promotes glioma cell proliferation, reduces apoptosis, and correlates with poor survival of patients. Nonetheless, the function of miR‑146b‑5p in temozolomide resistance remains unclear...
September 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048673/the-ethanol-extracts-of-sporoderm-broken-spores-of-ganoderma-lucidum-inhibit-colorectal-cancer-in-vitro-and-in-vivo
#20
Kang Li, Kun Na, Tingting Sang, Kaikai Wu, Ying Wang, Xingya Wang
The medicinal mushroom Ganoderma lucidum (G. lucidum) has been reported to possess a variety of pharmacological activities including anticancer effects. However, the anti-colorectal cancer effects and the potential molecular mechanisms of the ethanol extracts of sporoderm-broken spores of G. lucidum (BSGLEE), which mainly contains triterpenoids, have not been reported. The aim of the present study was to investigate the anticancer effects and molecular mechanisms exerted by BSGLEE on colorectal cancer in vitro and in vivo...
September 27, 2017: Oncology Reports
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