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Chloroquine and cancer

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https://www.readbyqxmd.com/read/28726781/autophagy-inhibition-reduces-chemoresistance-and-tumorigenic-potential-of-human-ovarian-cancer-stem-cells
#1
Anna Pagotto, Giorgia Pilotto, Elena Laura Mazzoldi, Maria Ornella Nicoletto, Simona Frezzini, Anna Pastò, Alberto Amadori
Epithelial ovarian cancer (EOC) is one of the most malignant gynecological tumors with a high mortality rate owing to tumor relapse after anticancer therapies. It is widely accepted that a rare tumor cell population, known as cancer stem cells (CSC), is responsible for tumor progression and relapse; intriguingly, these cells are able to survive nutrient starvation (such as in vitro culture in the absence of glucose) and chemotherapy treatment. Recent data also indicated that chemotherapy resistance is associated with autophagy activation...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28724415/identification-and-characterization-of-the-antiplasmodial-activity-of-hsp90-inhibitors
#2
Claribel Murillo-Solano, Chunmin Dong, Cecilia G Sanchez, Juan C Pizarro
BACKGROUND: The recent reduction in mortality due to malaria is being threatened by the appearance of Plasmodium falciparum parasites that are resistant to artemisinin in Southeast Asia. To limit the impact of resistant parasites and their spread across the world, there is a need to validate anti-malarial drug targets and identify new leads that will serve as foundations for future drug development programmes targeting malaria. Towards that end, the antiplasmodial potential of several Hsp90 inhibitors was characterized...
July 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28708385/chloroquine-modified-hydroxyethyl-starch-as-a-polymeric-drug-for-cancer-therapy
#3
Richard Sleightholm, Bin Yang, Fei Yu, Ying Xie, David Oupický
Hydroxyethyl starch (HES) is a clinically used polysaccharide colloidal plasma volume expander. The goal of this study was to synthesize HES modified with hydroxychloroquine (HCQ) as a novel polymeric drug with the ability to inhibit the invasive character of pancreatic cancer (PC) cells. HES was conjugated with HCQ using a simple carbonyldiimidazole coupling to prepare Chloroquine-modified HES (CQ-HES). CQ-HES with various degrees of HCQ substitution were synthesized and characterized. Atomic force microscopy was used to demonstrate a pH-dependent assembly of CQ-HES into well-defined nanoparticles...
July 14, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28707966/targeted-molecular-ablation-of-cancer-stem-cells-for-curing-gastrointestinal-cancers
#4
Yong Seok Kim, Ho Jae Lee, Jong-Min Park, Young-Min Han, Napapan Kangwan, Ji Young Oh, Dong Yoon Lee, Ki Baik Hahm
Abundance of the ATPase-binding cassette (ABC) transporters and deranged self-renewal pathways characterize the presence of cancer stem cells (CSCs) in gastrointestinal cancers (GI cancers), which play crucial roles in tumorigenesis, chemotherapy resistance, tumor recurrence, and cancer metastasis. Therefore, in order to ensure high cure rates, chemoquiescence, CSCs should be ablated. Recent advances in either understanding CSCs or biomarker identification enable scientists to develop techniques for ablating CSCs and clinicians to provide cancer cure, especially in GI cancers characterized by inflammation-driven carcinogenesis...
July 14, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28676644/blocking-autophagy-improves-the-anti-tumor-activity-of-afatinib-in-lung-adenocarcinoma-with-activating-egfr-mutations-in-vitro-and-in-vivo
#5
Xiangxiang Hu, Si Shi, Huan Wang, Xiaochen Yu, Qian Wang, Shanshan Jiang, Dianwen Ju, Li Ye, Meiqing Feng
Afatinib, a second-generation tyrosine kinase inhibitor (TKI), has been approved for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC). However, afatinib's clinical application is still hampered by acquired resistance. Recently, autophagy is considered as an important mechanism of resistance to TKI. Herein, we investigated the autophagy induction as well as its influence on anti-lung adenocarcinoma activity of afatinib in two activating EGFR-mutants H1975 and H1650 cells. First, Growth inhibition and caspase-dependent apoptosis were observed in afatinib-treated H1975 and H1650 cells...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28676397/feedback-autophagy-activation-as-a-key-resistance-factor-of-ku-0060648-in-colorectal-cancer-cells
#6
Mintao Mao, Yumei Liu, Xinhai Gao
The current study evaluated the potential anti-colorectal cancer (CRC) activity by Ku-0060648, a novel DNA-PKcs and PI3K duel inhibitor. In both CRC cell lines (HCT-116 and HT-29) and primary human colon cancer cells, Ku-0060648 exposure at nM concentrations efficiently inhibited cell proliferation. Meanwhile, Ku-0060648 provoked apoptosis in CRC cells. Ku-0060648 was yet ineffective to the normal colon epithelial cells. Ku-0060648 blocked PI3K-AKT-mTOR cascade and in-activated DNA-PKcs in CRC cells. Intriguingly, Ku-0060648 treatment induced feedback autophagy activation in HCT-116 cells...
July 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28675807/autophagy-inhibition-enabled-efficient-photothermal-therapy-at-a-mild-temperature
#7
Zhengjie Zhou, Yang Yan, Kewen Hu, Yuan Zou, Yiwen Li, Rui Ma, Qiang Zhang, Yiyun Cheng
The heterogeneously-distributed hyperthermia in nanomaterial-mediated photothermal therapy commonly results in incomplete tumor eradication and serious damage of health tissue. Here, we found autophagy was activated in cancer cells underwent photothermal therapy and the inhibition of autophagy significantly enhanced the efficacy of photothermal killing of cancer cells. A formulation of chloroquine-loaded polydopamine nanoparticles was developed for sensitized photothermal cancer therapy, and the in vitro and in vivo study demonstrated that inhibition of autophagy remarkably augmented the efficacy of photothermal therapy, leading to efficient tumor suppression at a mild temperature...
June 27, 2017: Biomaterials
https://www.readbyqxmd.com/read/28664293/targeting-autophagy-to-modulate-cell-survival-a-comparative-analysis-in-cancer-normal-and-embryonic-cells
#8
Aleksandra Divac Rankov, Mila Ljujić, Marija Petrić, Dragica Radojković, Milica Pešić, Jelena Dinić
Autophagy is linked to multiple cancer-related signaling pathways, and represents a defense mechanism for cancer cells under therapeutic stress. The crosstalk between apoptosis and autophagy is essential for both tumorigenesis and embryonic development. We studied the influence of autophagy on cell survival in pro-apoptotic conditions induced by anticancer drugs in three model systems: human cancer cells (NCI-H460, COR-L23 and U87), human normal cells (HaCaT and MRC-5) and zebrafish embryos (Danio rerio). Autophagy induction with AZD2014 and tamoxifen antagonized the pro-apoptotic effect of chemotherapeutics doxorubicin and cisplatin in cell lines, while autophagy inhibition by wortmannin and chloroquine synergized the action of both anticancer agents...
June 29, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28640657/retinal-findings-on-oct-in-systemic-conditions
#9
Preeti Patil Chhablani, Vikas Ambiya, Akshay G Nair, Sailaja Bondalapati, Jay Chhablani
PURPOSE: Imaging technology has advanced by leaps and bounds in the recent past and has resulted in a much greater understanding of ocular diseases. The aim of this review article is to summarize optical coherence tomography (OCT) findings of various systemic conditions. METHOD: A systematic literature search of the Medline/PubMed database was performed. English articles up to April 2015 were included. Terms used for search included: Alzheimer's Disease; Multiple Sclerosis; Parkinson's Disease; Behçet's Disease; Schizophrenia; Migraine; Obstructive Sleep Apnea Syndrome; Neurofibromatosis; Sickle Cell Disease; Renal diseases; Lupus Retinopathy; Valsalva Retinopathy; Whiplash Retinopathy; Shaken-Baby Syndrome; Choroidal metastases; Intracranial Hypertension; Drug toxicity; Deferoxamine; Sildenafil; Tamoxifen; Hydroxychloroquine; Chloroquine; Ethambutol; Lead; Sickle Cell Disease; and Thalassemia along with OCT...
June 22, 2017: Seminars in Ophthalmology
https://www.readbyqxmd.com/read/28637004/autophagy-is-required-for-crizotinib-induced-apoptosis-in-met-amplified-gastric-cancer-cells
#10
Rebecca D Schroeder, Woonyoung Choi, David S Hong, David J McConkey
MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug-sensitive cells in a concentration-dependent manner...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28627629/reducing-autophagy-and-inducing-g1-phase-arrest-by-aloperine-enhances-radio-sensitivity-in-lung-cancer-cells
#11
Zhijie Xu, Yuanliang Yan, Shuangshuang Zeng, Long Qian, Shuang Dai, Lingfang Xiao, Lin Wang, Xue Yang, Yi Xiao, Zhicheng Gong
Aloperine (ALO), an isolated alkaloid from the leaves of Sophora alopecuroides (S. alopecuroides), has been suggested to exhibit anti-inflammatory and antitumor properties, and has been traditionally used to treat various diseases, including cancers. However, little is known about the effects of ALO on the radio-sensitivity of lung cancer cells. In the present study, we confirmed that agent ALO inhibits cell growth, promotes cell aopotosis and induces G1 phase arrest and consequently enhanced the radio-sensitivity in radio-resistant lung cancer cells A549/IR...
June 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28622697/vitamin-c-and-doxycycline-a-synthetic-lethal-combination-therapy-targeting-metabolic-flexibility-in-cancer-stem-cells-cscs
#12
Ernestina Marianna De Francesco, Gloria Bonuccelli, Marcello Maggiolini, Federica Sotgia, Michael P Lisanti
Here, we developed a new synthetic lethal strategy for further optimizing the eradication of cancer stem cells (CSCs). Briefly, we show that chronic treatment with the FDA-approved antibiotic Doxycycline effectively reduces cellular respiration, by targeting mitochondrial protein translation. The expression of four mitochondrial DNA encoded proteins (MT-ND3, MT-CO2, MT-ATP6 and MT-ATP8) is suppressed, by up to 35-fold. This high selection pressure metabolically synchronizes the surviving cancer cell sub-population towards a predominantly glycolytic phenotype, resulting in metabolic inflexibility...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620137/biological-specificity-of-cdk4-6-inhibitors-dose-response-relationship-in-vivo-signaling-and-composite-response-signature
#13
Erik S Knudsen, Jack Hutcheson, Paris Vail, Agnieszka K Witkiewicz
Recently developed potent and selective CDK4/6 inhibitors fall into two classes based on structure and toxicity profiles in clinical studies. One class, exemplified by palbociclib and ribociclib, exhibits neutropenia as a dose-limiting toxicity and requires discontinuous dosing. In contrast, the structurally distinct CDK4/6 inhibitor abemaciclib is dosed continuously, and has diarrhea and fatigue as dose-limiting toxicities. In preclinical models, palbociclib has been extensively studied and induces cell cycle inhibition in an RB-dependent manner...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28615100/-the-mechanism-underlying-the-effects-of-tea-polyphenol-on-epirubicin-induced-autophagy-and-apoptosis-in-t24-bladder-cancer-cells
#14
Wen Gu, Hubin Yin, Yan Liu, Xin Gou
Objective To investigate the mechanism by which epirubicin (EPI) induces autophagy and the mechanism by which tea polyphenol (TP) regulates EPI-induced autophagy and apoptosis in T24 bladder cancer cells. Methods T24 cells weredivided into control group, EPI group, TP group and TP plus EPI group. Eight hours after corresponding treatments in different groups, transmission electron microscopy (TEM) was used to observe the image of autophagosomes. The expressions of autophagy-related protein LC3II and p62 in the cells were detected by Western blotting...
June 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28611197/treatment-of-pancreatic-cancer-patient-derived-xenograft-panel-with-metabolic-inhibitors-reveals-efficacy-of-phenformin
#15
N V Rajeshkumar, Shinichi Yabuuchi, Shweta Pai, Elizabeth De Oliveira, Jurre J Kamphorst, Joshua D Rabinowitz, Héctor Tejero, Fatima Al-Shahrour, Manuel Hidalgo, Anirban Maitra, Chi V Dang
Purpose: To identify effective metabolic inhibitors to suppress the aggressive growth of pancreatic ductal adenocarcinoma (PDAC), we explored the in vivo anti-tumor efficacy of metabolic inhibitors in a panel of patient-derived PDAC xenograft models (PDXs), and investigated whether genomic alterations of tumors correlate with the sensitivity to metabolic inhibitors. <p>Experimental Design: Mice with PDAC tumors from six to thirteen individual PDXs were randomized and treated, once daily for 4 weeks, with either PBS (vehicle) or the glutaminase inhibitor BPTES, transaminase inhibitor aminooxyacetate (AOA), pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA), autophagy inhibitor chloroquine (CQ), mitochondrial complex I inhibitor phenformin/metformin...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28601826/study-protocol-of-a-phase-ib-ii-clinical-trial-of-metformin-and-chloroquine-in-patients-with-idh1-mutated-or-idh2-mutated-solid-tumours
#16
Remco J Molenaar, Robert Js Coelen, Mohammed Khurshed, Eva Roos, Matthan Wa Caan, Myra E van Linde, Mathilde Kouwenhoven, Jos Am Bramer, Judith Vmg Bovée, Ron A Mathôt, Heinz-Josef Klümpen, Hanneke Wm van Laarhoven, Cornelis Jf van Noorden, W Peter Vandertop, Hans Gelderblom, Thomas M van Gulik, Johanna W Wilmink
INTRODUCTION: High-grade chondrosarcoma, high-grade glioma and intrahepatic cholangiocarcinoma are aggressive types of cancer with a dismal outcome. This is due to the lack of effective treatment options, emphasising the need for novel therapies. Mutations in the genes IDH1 and IDH2 (isocitrate dehydrogenase 1 and 2) occur in 60% of chondrosarcoma, 80% of WHO grade II-IV glioma and 20% of intrahepatic cholangiocarcinoma. IDH1/2-mutated cancer cells produce the oncometabolite D-2-hydroxyglutarate (D-2HG) and are metabolically vulnerable to treatment with the oral antidiabetic metformin and the oral antimalarial drug chloroquine...
June 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28599416/autophagy-inhibition-impairs-the-epithelial-mesenchymal-transition-and-enhances-cisplatin-sensitivity-in-nasopharyngeal-carcinoma
#17
Zhongwu Su, Guo Li, Chao Liu, Shuling Ren, Tengbo Deng, Shuiting Zhang, Yongquan Tian, Yong Liu, Yuanzheng Qiu
Drug resistance restricts the efficacy of cisplatin in the treatment of nasopharyngeal carcinoma (NPC). Increasing evidence indicates that autophagy and the epithelial-mesenchymal transition (EMT) participate in cancer progression and drug sensitivity. The aim of the present study was to investigate the function of autophagy and EMT in cisplatin treatment, and to reveal the underlying impact of autophagy on the EMT process in NPC. Transmission electron microscopy assays and western blot analyses confirmed that cisplatin activates autophagy in NPC cells...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28597984/dual-inhibition-of-bdnf-trkb-and-autophagy-a-promising-therapeutic-approach-for-colorectal-cancer
#18
Clément Mazouffre, Sophie Geyl, Aurélie Perraud, Sabrina Blondy, Marie-Odile Jauberteau, Muriel Mathonnet, Mireille Verdier
Colorectal cancer (CRC) is the most common digestive cancer in the Western world. Despite effective therapies, resistance and/or recurrence frequently occur. The present study investigated the impact of two survival pathways-neurotrophic factors (TrkB/BDNF) and autophagy-on cell fate and tumour evolution. In vitro studies were performed on two CRC cell lines, SW480 (primary tumour) and SW620 (lymph node invasion), which were also used for subcutaneous xenografts on a nude mouse model. In addition, the presence of neurotrophic factors (NTs) and autophagy markers were assessed in tissue samples representative of different stages...
June 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28596679/oxidative-stress-induced-mitochondrial-dysfunction-in-a-normal-colon-epithelial-cell-line
#19
Nandakumar Packiriswamy, Kari F Coulson, Susan J Holcombe, Lorraine M Sordillo
AIM: To determine how a normal human colon cell line reacts to microbial challenge as a way to study oxidative stress-induced responses associated with inflammatory bowel disease. METHODS: Normal human colon epithelial cells (ATCC(®) CRL.1790™) were stimulated with either heat killed E. coli or heat killed murine cecal contents (HKC) and examined for several relevant biomarkers associated with inflammation and oxidative stress including cytokine production, mitochondrial autophagy and oxidant status...
May 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28592712/high-serum-hdgf-levels-are-predictive-of-bone-metastasis-and-unfavorable-prognosis-in-non-small-cell-lung-cancer
#20
Guorong Zhang, Zhiqiang Liu, Yan Chen, Yihang Zhang
Hepatoma-derived growth factor (HDGF) is a heparin-binding protein possessing mitogenic activity and could be secreted from necrotic cells passively or actively, thereby functioning as a damage-associated molecular pattern (DAMP). The high expression of HDGF in non-small cell lung cancer (NSCLC) tissues is associated with unfavorable prognosis. However, the clinical significance of serum HDGF has not been elucidated in NSCLC yet. In the present study, we compared the serum levels of HDGF in 235 patients with NSCLC (141 adenocarcinoma and 94 squamous cell carcinoma cases) with those in 40 healthy subjects...
2017: Tohoku Journal of Experimental Medicine
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