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https://www.readbyqxmd.com/read/28941356/computational-approaches-to-identify-genetic-interactions-for-cancer-therapeutics
#1
Graeme Benstead-Hume, Sarah K Wooller, Frances M G Pearl
The development of improved cancer therapies is frequently cited as an urgent unmet medical need. Here we describe how genetic interactions are being therapeutically exploited to identify novel targeted treatments for cancer. We discuss the current methodologies that use 'omics data to identify genetic interactions, in particular focusing on synthetic sickness lethality (SSL) and synthetic dosage lethality (SDL). We describe the experimental and computational approaches undertaken both in humans and model organisms to identify these interactions...
September 23, 2017: Journal of Integrative Bioinformatics
https://www.readbyqxmd.com/read/28938672/comparing-the-clinical-efficacy-of-abiraterone-acetate-enzalutamide-and-orteronel-in-patients-with-metastatic-castration-resistant-prostate-cancer-by-performing-a-network-meta-analysis-of-eight-randomized-controlled-trials
#2
Minyong Kang, Chang Wook Jeong, Cheol Kwak, Ja Hyeon Ku, Hyeon Hoe Kim
Various novel androgen receptor (AR) targeting drugs have been developed recently and have shown beneficial effects on survival in patients with metastatic castration-resistant prostate cancer (mCRPC). However, no consensus has been reached regarding which of these agents provides the most favorable oncological outcomes. Here, we aimed to compare the efficacy of novel AR-targeted agents by performing a network meta-analysis of randomized controlled trials (RCTs). We included eight RCTs for men with mCRPC treated with one of the AR targeting agents: abiraterone acetate, enzalutamide, or orteronel...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938620/pathological-expression-of-tissue-factor-confers-promising-antitumor-response-to-a-novel-therapeutic-antibody-sc1-in-triple-negative-breast-cancer-and-pancreatic-adenocarcinoma
#3
Xuesai Zhang, Qingrou Li, Hui Zhao, Lanping Ma, Tao Meng, Jianchang Qian, Rui Jin, Jingkang Shen, Ker Yu
The pathological presence of tissue factor (TF) in cancer cells promotes tumor-initiated thrombosis and cancer metastasis. We found that TF is aberrantly present in large percentage of aggressive triple negative breast cancer (TNBC) and pancreatic adenocarcinoma (PaC), two most lethal forms of malignancy that urgently need effective treatment. TF expression in TNBC clustered with higher levels of vimentin, basal-type keratins KRT5/14 and caveolin-1 but lower levels of luminal-type biomarkers. We developed a novel and specific anti-TF therapeutic antibody SC1, which displayed an exceedingly high potency against TF extracellular domain (EC50: 0...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938616/identification-of-potential-cancer-related-pseudogenes-in-lung-adenocarcinoma-based-on-cerna-hypothesis
#4
Yunzhen Wei, Zhiqiang Chang, Cheng Wu, Yinling Zhu, Kun Li, Yan Xu
Pseudogenes are initially regarded as non-functional genomic fossils resulted from inactivating gene mutations during evolution. Far from being silent, pseudogenes are proved to regulate the expression of protein-coding genes through function as microRNA sponge in vivo. The aim of our study was to propose an integrative systems biology approach to identify disease pseudogenes base on competitive endogenous RNA (ceRNA) hypothesis. Here, we applied our method to lung adenocarcinoma (LUAD) RNASeq data from TCGA and identified 33 candidate pseudogenes...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938600/application-of-dual-targeting-drug-delivery-system-for-the-improvement-of-anti-glioma-efficacy-of-doxorubicin
#5
Zhenliang Sun, Xuebing Yan, YiBo Liu, Linsheng Huang, Cheng Kong, Xiao Qu, Man Wang, Renyuan Gao, Huanlong Qin
Chemotherapy of glioma is always hampered by the unsatisfactory tumor accumulation of drugs, of which the most noticeable obstacle is the limited drug permeability from vessels into tumor inner. In the present study, we developed a novel nanocarrier for the delivery of doxorubicin to brain tumor. Such novel drug delivery system was mainly composed of a tumor homing peptide and DOX-loaded PLA nanoparticles (AP1-NP-DOX). CRKRLDRNC peptide, named as AP1, was a newly glioma affinity peptide which could specifically binds to interleukin-4 receptor (IL-4R), highly expressing on both glioma cells and angiogenesis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938577/mitochondria-chaperone-grp75-moonlighting-as-a-cell-cycle-controller-to-derail-endocytosis-provides-an-opportunity-for-nanomicrosphere-intracellular-delivery
#6
Zhihui Gao, Xiuran Niu, Qing Zhang, Hang Chen, Aiai Gao, Shanshan Qi, Rong Xiang, Mattias Belting, Sihe Zhang
Understanding how cancer cells regulate endocytosis during the cell cycle could lead us to capitalize this event pharmacologically. Although certain endocytosis pathways are attenuated during mitosis, the endocytosis shift and regulation during the cell cycle have not been well clarified. The conventional concept of glucose-regulated proteins (GRPs) as protein folding chaperones was updated by discoveries that translocated GRPs assume moonlighting functions that modify the immune response, regulate viral release, and control intracellular trafficking...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938559/doxorubicin-loaded-platelets-conjugated-with-anti-cd22-mabs-a-novel-targeted-delivery-system-for-lymphoma-treatment-with-cardiopulmonary-avoidance
#7
Peipei Xu, Huaqin Zuo, Rongfu Zhou, Fan Wang, Xu Liu, Jian Ouyang, Bing Chen
B-cell lymphoma accounts for approximately 85% of all adult non-Hodgkin's lymphoma cases. Doxorubicin (DOX) is an indispensable drug for the treatment of non-Hodgkin's lymphoma. However, DOX causes severe cardiotoxicity, which limits its use in conventional treatment strategies. In this study, we developed a novel drug delivery system for lymphoma treatment: DOX-loaded platelets that were conjugated with anti-CD22 monoclonal antibodies (mAbs) (DOX-platelet-CD22). Platelets are bio- and immune-compatible drug carriers that can prolong the circulation time of drugs...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938558/human-menstrual-blood-derived-mesenchymal-stem-cells-as-a-cellular-vehicle-for-malignant-glioma-gene-therapy
#8
Xiao-Jun Wang, Bing-Yu Xiang, Ya-Hui Ding, Lu Chen, Hai Zou, Xiao-Zhou Mou, Charlie Xiang
Despite many advances in conventional treatment strategies, there is no effective treatment modality for malignant gliomas. Gene therapy may offer a promising option for gliomas and several gene therapy approaches have shown anti-tumor efficiency in previous studies. Mesenchymal stem cell-based gene therapies, in which stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential because of their innate homing ability. In this study, human menstrual blood-derived MSCs (MenSC), a novel type of multipotential MSCs displays tropism for human malignant glioma when used as a gene delivery vehicle for therapeutics...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938552/novel-pleiotropic-effects-of-bioactive-phospholipids-in-human-lung-cancer-metastasis
#9
Gabriela Schneider, Zachariah Payne Sellers, Kamila Bujko, Sham S Kakar, Magda Kucia, Mariusz Z Ratajczak
We previously proposed that one of the unwanted side effects of chemotherapy and radiotherapy is the increase in several peptide- and non-peptide based chemoattractants in damaged tissues, leading to induction of a prometastatic microenvironment for remaining cancer cells. Herein, we turned out our attention to a potential role of bioactive phospholipids (BphsLs), such as sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), lysophosphatidylcholine (LPC), and lysophosphatidic acid (LPA) in lung cancer (LC) metastasis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938544/sialyllactose-suppresses-angiogenesis-by-inhibiting-vegfr-2-activation-and-tumor-progression
#10
Tae-Wook Chung, Eun-Young Kim, Seok-Jo Kim, Hee-Jung Choi, Se Bok Jang, Keuk-Jun Kim, Sun-Hyung Ha, Fukushi Abekura, Choong-Hwan Kwak, Cheorl-Ho Kim, Ki-Tae Ha
The oligosaccharides in human milk have various biological functions. However, the molecular mechanism(s) underlying the anti-angiogenic action of sialylated human milk oligosaccharides (HMOs) are still unclear. Here, we show that siallylactose (SL) found in human milk can inhibit the activation of vascular endothelial growth factor (VEGF)-mediated VEGF receptor-2 (VEGFR-2) by binding to its VEGF binding site (second and third IgG-like domains), thus blocking downstream signal activation. SL also inhibits growth of VEGF-stimulated endothelial cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938517/green-tea-camellia-sinensis-and-l-theanine-medicinal-values-and-beneficial-applications-in-humans-a-comprehensive-review
#11
REVIEW
Muhammad Saeed, Muhammad Naveed, Muhammad Arif, Mohib Ullah Kakar, Robina Manzoor, Mohamed Ezzat Abd El-Hack, Mahmoud Alagawany, Ruchi Tiwari, Rekha Khandia, Ashok Munjal, Kumaragurubaran Karthik, Kuldeep Dhama, Hafiz M N Iqbal, Maryam Dadar, Chao Sun
Green tea (Camellia sinensis) is a famous herb, and its extract has been extensively used in traditional Chinese medicinal system. In this context, several studies have revealed its health benefits and medicinal potentialities for several ailments. With ever increasing scientific knowledge, search for safer, potential and novel type of health-related supplements quest, scientists are re-directing their research interests to explore natural resources i.e. medicinal herbs/plant derived compounds. Green tea consumption has gained a special attention and popularity in the modern era of changing lifestyle...
September 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28938010/epidermal-growth-factor-receptor-targeted-sonoporation-with-microbubbles-enhances-therapeutic-efficacy-in-a-squamous-cell-carcinoma-model
#12
Fumika Hirabayashi, Kenjiro Iwanaga, Toshinori Okinaga, Osamu Takahashi, Wataru Ariyoshi, Ryo Suzuki, Mutsumi Sugii, Kazuo Maruyama, Kazuhiro Tominaga, Tatsuji Nishihara
Sonoporation is a drug and gene delivery system using ultrasonication that allows the intracellular delivery of foreign molecules that cannot enter cells under normal conditions. We previously reported that sonoporation with microbubbles (MBs) could achieve effective intracellular drug delivery to human gingival squamous carcinoma Ca9-22 cells. In this study, we developed anti-epidermal growth factor receptor (EGFR) antibody-conjugated MBs (EGFR-MBs) and evaluated their capacity to enhance anti-cancer drug toxicity in vitro and in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28937657/synthesis-of-2-4-diaminopyrimidine-core-based-derivatives-and-biological-evaluation-of-their-anti-tubercular-activities
#13
Yifan Ouyang, Hao Yang, Peng Zhang, Yu Wang, Sargit Kaur, Xuanli Zhu, Zhe Wang, Yutong Sun, Wei Hong, Yun Fong Ngeow, Hao Wang
Tuberculosis (TB) is a chronic, potentially fatal disease caused by Mycobacterium tuberculosis (Mtb). The dihyrofolate reductase in Mtb (mt-DHFR) is believed to be an important drug target in anti-TB drug development. This enzyme contains a glycerol (GOL) binding site, which is assumed to be a useful site to improve the selectivity towards human dihyrofolate reductase (h-DHFR). There have been previous attempts to design drugs targeting the GOL binding site, but the designed compounds contain a hydrophilic group, which may prevent the compounds from crossing the cell wall of Mtb to function at the whole cell level...
September 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28937624/therapeutic-mechanisms-of-vernonia-amygdalina-delile-in-the-treatment-of-prostate-cancer
#14
William Johnson, Paul B Tchounwou, Clement G Yedjou
Prostate cancer patients have been suffering from limited treatment options due to late diagnosis, poor drug tolerance, and multi-drug resistance to almost all the current drug treatments. Therefore, it is important to seek a new alternative therapeutic medicine that can effectively prevent the disease and even eradicate the progression and metastasis of prostate cancer. Vernonia amygdalina Delile (VAD) is a common edible vegetable in Cameroon that has been used as a traditional medicine for some human diseases...
September 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28937581/thrombosis-on-a-left-atrial-appendage-occluder-device-the-double-edged-sword-of-stroke-prevention-strategies-in-atrial-fibrillation
#15
Giuseppe Ciconte, Manuel Conti, Mario Baldi, Massimo Saviano, Gabriele Vicedomini, Carlo Pappone
: A huge thrombus, developing after percutaneous left atrial appendage occlusion, has been successfully treated with dabigatran and aspirin as combination therapy.Although novel oral anticoagulants alone may be effective in thrombus dissolution, the association of an antiplatelet drug may safely enhance this process.
September 20, 2017: Journal of Cardiovascular Medicine
https://www.readbyqxmd.com/read/28936721/a-novel-resveratrol-derivative-selectively-inhibits-the-proliferation-of-colorectal-cancer-cells-with-kras-mutation
#16
Haruna Okamoto, Taiji Matsukawa, Satoshi Doi, Toshiyuki Tsunoda, Yuuga Sawata, Madoka Naemura, Koichiro Ohnuki, Senji Shirasawa, Yojiro Kotake
Resveratrol is a polyphenolic compound in many edible foods including grapes, peanuts, and berries. Several studies have revealed the beneficial effects of resveratrol against various diseases such as heart disease, diabetes, obesity, neurological disorders, and cancer. A recent study showed that resveratrol inhibits the proliferation of HCT116 human colorectal cancer cells in three-dimensional culture (3DC) via induction of luminal apoptosis in HCT116 cell spheroids. In this study, we showed that a novel compound, caffeic acid-adducted resveratrol, has a stronger inhibitory effect on the growth of HCT116 cell spheroids in 3DC than resveratrol...
September 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28936710/cloning-expression-purification-and-bioactivity-evaluation-of-a-thrombin-like-enzyme-from-deinagkistrodon-acutus-venom-gland-library
#17
An Li, Chuan Zhang, Jie Wang, Junjie Wang, Hailong Jiang, Jianzhong Li, Xingyuan Ma, Wen Zhang, Yiming Lu
OBJECTIVES: To identify a new member of serine proteases from Deinagkistrodon acutus via phage display technique and appraise its biocatalytic activities. RESULTS: A novel thrombin-like enzyme gene was cloned by screening the phage display library of D. acutus venom gland. The gene has a 783 bp ORF encoding 260 amino acids. A recombinant enzyme expression vector was constructed and the fused protein was expressed in Escherichia coli. The protein was purified showing a single band of approx...
September 21, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28936405/chemotherapy-for-hepatocellular-carcinoma-current-evidence-and-future-perspectives
#18
REVIEW
Emanuele Rinninella, Lucia Cerrito, Irene Spinelli, Marco Cintoni, Maria Cristina Mele, Maurizio Pompili, Antonio Gasbarrini
Hepatocarcinogenesis is a multistep process, heralded by abnormalities in cell differentiation and proliferation and sustained by an aberrant neoangiogenesis. Understanding the underlying molecular pathogenesis leading to hepatocellular carcinoma is a prerequisite to develop new drugs that will hamper or block the steps of these pathways. As hepatocellular carcinoma has higher arterial vascularization than normal liver, this could be a good target for novel molecular therapies. Introduction of the antiangiogenic drug sorafenib into clinical practice since 2008 has led to new perspectives in the management of this tumor...
September 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28936389/disease-progression-modeling-key-concepts-and-recent-developments
#19
Sarah F Cook, Robert R Bies
Disease modeling involves the use of mathematical functions to describe quantitatively the time course of disease progression. In order to characterize the natural progression of disease, these models generally incorporate longitudinal data for some biomarker(s) of disease severity or can incorporate more direct measures of disease severity. Disease models are also often linked to pharmacokinetic-pharmacodynamic models so that the influence of drug treatment on disease progression can be quantified and evaluated...
October 2016: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28935948/novel-scaffolds-for-inhibition-of-cruzipain-identified-from-high-throughput-screening-of-anti-kinetoplastid-chemical-boxes
#20
Emir Salas-Sarduy, Lionel Urán Landaburu, Joel X Karpiak, Kevin P Madauss, Juan José Cazzulo, Fernán Agüero, Vanina Eder Alvarez
American Trypanosomiasis or Chagas disease is a prevalent, neglected and serious debilitating illness caused by the kinetoplastid protozoan parasite Trypanosoma cruzi. The current chemotherapy is limited only to nifurtimox and benznidazole, two drugs that have poor efficacy in the chronic phase and are rather toxic. In this scenario, more efficacious and safer drugs, preferentially acting through a different mechanism of action and directed against novel targets, are particularly welcome. Cruzipain, the main papain-like cysteine peptidase of T...
September 21, 2017: Scientific Reports
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