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Targeted cancer therapy molecular level

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https://www.readbyqxmd.com/read/28633205/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#1
EDITORIAL
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, Timothy J Baldwin
The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group of experts from June 2 to 3, 2016, in Bethesda, Maryland, to develop NHLBI recommendations aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MCS devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
July 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28625953/the-relationship-between-the-expressions-of-tumor-associated-fibroblasts-cav-1-and-mct4-and-the-prognosis-of-papillary-carcinoma-of-breast
#2
Yuanyuan Zhai, Lijun Chai, Jianzhong Chen
The aim of this study was to evaluate the expression levels of Cav-1 and MCT4 in the tumor stroma CAFs. Immunohistochemical method was used to detect the expression of Cav-1 and MCT4 in 86 cases of IMPC, with 105 cases of non-specific invasive ductal carcinoma (IDC-NOS) as control. Their differential expression in different histological types were compared and relationship between the expression of Cav-1 and IMPC in the MCT4 and the main pathological features such as age, tumor size and histological grades were analyzed...
January 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28623259/microrna-34a-encapsulated-in-hyaluronic-acid-nanoparticles-induces-epigenetic-changes-with-altered-mitochondrial-bioenergetics-and-apoptosis-in-non-small-cell-lung-cancer-cells
#3
Malav Trivedi, Amit Singh, Meghna Talekar, Grishma Pawar, Parin Shah, Mansoor Amiji
Therapies targeting epigenetic changes for cancer treatment are in Phase I/II trials; however, all of these target only nuclear DNA. Emerging evidence suggests presence of methylation marks on mitochondrial DNA (mtDNA); but their contribution in cancer is unidentified. Expression of genes encoded on mtDNA are altered in cancer cells, along with increased glycolytic flux. Such glycolytic flux and elevated reactive oxygen species is supported by increased antioxidant; glutathione. MicroRNA-34a can translocate to mitochondria, mediate downstream apoptotic effects of tumor suppressor P53, and inhibit the antioxidant response element Nrf-2, resulting in depleted glutathione levels...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28621802/glypican-3-a-promising-biomarker-for-hepatocellular-carcinoma-diagnosis-and-treatment
#4
REVIEW
Fubo Zhou, Wenting Shang, Xiaoling Yu, Jie Tian
Liver cancer is the second leading cause of cancer-related deaths, and hepatocellular carcinoma (HCC) is the most common type. Therefore, molecular targets are urgently required for the early detection of HCC and the development of novel therapeutic approaches. Glypican-3 (GPC3), an oncofetal proteoglycan anchored to the cell membrane, is normally detected in the fetal liver but not in the healthy adult liver. However, in HCC patients, GPC3 is overexpressed at both the gene and protein levels, and its expression predicts a poor prognosis...
June 16, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28620146/mitochondrial-asncmtrna-1-and-asncmtrna-2-as-potent-targets-to-inhibit-tumor-growth-and-metastasis-in-the-renca-murine-renal-adenocarcinoma-model
#5
Vincenzo Borgna, Jaime Villegas, Verónica A Burzio, Sebastián Belmar, Mariela Araya, Emanuel Jeldes, Lorena Lobos-González, Verónica Silva, Claudio Villota, Luciana Oliveira-Cruz, Constanza Lopez, Teresa Socias, Octavio Castillo, Luis O Burzio
Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28618420/heterogeneity-in-gastric-cancer-from-pure-morphology-to-molecular-classifications
#6
Irene Gullo, Fátima Carneiro, Carla Oliveira, Gabriela M Almeida
Gastric cancer (GC) represents a global health concern. Despite advances in prevention, diagnosis, and therapy, GC is still the third leading cause of cancer mortality worldwide, with more than 720,000 estimated deaths in 2012. Overall survival for advanced disease is about 1 year, a dismal prognosis that is partly due to the high levels of biological heterogeneity found in GC. Indeed, GC is a highly heterogeneous disease from morphological and molecular standpoints. The numerous histological and molecular classifications currently available reflect such heterogeneity...
June 16, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28616398/new-photodynamic-therapy-with-next-generation-photosensitizers
#7
REVIEW
Hiromi Kataoka, Hirotada Nishie, Noriyuki Hayashi, Mamoru Tanaka, Akihiro Nomoto, Shigenobu Yano, Takashi Joh
Photodynamic therapy (PDT) is a non-invasive antitumor treatment that uses the combination of a photosensitizer, tissue oxygen, and visible light irradiation to produce cytotoxic reactive oxygen species, predominantly singlet oxygen. Currently, first-generation PDT using porfimer sodium with an excimer dye laser, and second-generation PDT using talaporfin sodium PDT with a semiconductor laser are approved by health insurance for use in Japan. However, the cancer cell specificity and selectivity of these treatments are inadequate...
April 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28614715/phgdh-defines-a-metabolic-subtype-in-lung-adenocarcinomas-with-poor-prognosis
#8
Boxi Zhang, Adi Zheng, Per Hydbring, Gorbatchev Ambroise, Amanda Tomie Ouchida, Michel Goiny, Helin Vakifahmetoglu-Norberg, Erik Norberg
Molecular signatures are emerging determinants of choice of therapy for lung adenocarcinomas. An evolving therapeutic approach includes targeting metabolic dependencies in cancers. Here, using an integrative approach, we have dissected the metabolic fingerprints of lung adenocarcinomas, and we show that Phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in serine biosynthesis, is highly expressed in a adenocarcinoma subset with poor prognosis. This subset harbors a gene signature for DNA replication and proliferation...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28614631/trpm4-regulates-akt-gsk3-%C3%AE-activity-and-enhances-%C3%AE-catenin-signaling-and-cell-proliferation-in-prostate-cancer-cells
#9
Alfredo I Sagredo, Eduardo A Sagredo, Claudio Cappelli, Pablo Báez, Andaur M Rodrigo, Constanza Blanco, Julio C Tapia, César Echeverría, Oscar Cerda, Andrés Stutzin, Felipe Simon, Katherine Marcelain, Ricardo Armisén
Increased expression of the TRPM4 channel has been reported to be associated with the progression of prostate cancer. However, the molecular mechanism underlying its effect remains unknown. This work found that decreasing TRPM4 levels leads to the reduced proliferation of PC3 cells. This effect was associated with a decrease in total β-catenin protein levels and its nuclear localization, and a significant reduction in Tcf/Lef transcriptional activity. Moreover, TRPM4 silencing increases the Ser33/Ser37/Thr41 β-catenin phosphorylated population and reduces the phosphorylation of GSK-3β at Ser9, suggesting an increase in β-catenin degradation as the underlying mechanism...
June 14, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28614300/pten-counteracts-fbxl2-to-promote-ip3r3-and-ca-2-mediated-apoptosis-limiting-tumour-growth
#10
Shafi Kuchay, Carlotta Giorgi, Daniele Simoneschi, Julia Pagan, Sonia Missiroli, Anita Saraf, Laurence Florens, Michael P Washburn, Ana Collazo-Lorduy, Mireia Castillo-Martin, Carlos Cordon-Cardo, Said M Sebti, Paolo Pinton, Michele Pagano
In response to environmental cues that promote IP3 (inositol 1,4,5-trisphosphate) generation, IP3 receptors (IP3Rs) located on the endoplasmic reticulum allow the 'quasisynaptical' feeding of calcium to the mitochondria to promote oxidative phosphorylation. However, persistent Ca(2+) release results in mitochondrial Ca(2+) overload and consequent apoptosis. Among the three mammalian IP3Rs, IP3R3 appears to be the major player in Ca(2+)-dependent apoptosis. Here we show that the F-box protein FBXL2 (the receptor subunit of one of 69 human SCF (SKP1, CUL1, F-box protein) ubiquitin ligase complexes) binds IP3R3 and targets it for ubiquitin-, p97- and proteasome-mediated degradation to limit Ca(2+) influx into mitochondria...
June 14, 2017: Nature
https://www.readbyqxmd.com/read/28613101/targeting-igf1r-pathway-in-cancer-with-micrornas-how-close-are-we
#11
Arathy S Kumar, Suresh K Rayala, Ganesh Venkatraman
Cancer of the head and neck are the most common cancers in India and account for 30% of all cancers. At molecular level, it could be attributed to the over-expression of growth factors like IGF1-R, EGFR, VEGF-R and deregulation of cell cycle regulators and tumor suppressors. IGF1-R is an emerging target in head and neck cancer treatment, because of its reported role in tumor development, progression and metastasis. IGF1R targeted agents are in advanced stages of clinical development. Nevertheless, these agents suffer from several disadvantages including acquired resistance and toxic side effects...
June 14, 2017: RNA Biology
https://www.readbyqxmd.com/read/28611670/identification-of-epigallocatechin-3-gallate-as-an-inhibitor-of-phosphoglycerate-mutase-1
#12
Xiaoguang Li, Shuai Tang, Qian-Qian Wang, Elaine L-H Leung, Hongyue Jin, Yongzhuo Huang, Jia Liu, Meiyu Geng, Min Huang, Shengtao Yuan, Xiao-Jun Yao, Jian Ding
Targeting metabolic enzymes is believed to provide new therapeutic opportunities for cancer therapy. Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that importantly coordinates glycolysis, pentose phosphate pathway (PPP) flux and serine biosynthesis in cancer cells and hence gains increasing interest of inhibitor discovery. Only few PGAM1 inhibitors have been reported and the molecular potency remains very limited. In an effort to discover new PGAM1 inhibitors, we carried out a biochemical assay-based screen that was focused on natural products derived small molecule compounds...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28610954/feedback-regulation-of-aldoa-activates-the-hif-1%C3%AE-mmp9-axis-to-promote-lung-cancer-progression
#13
Yu-Chan Chang, Yung-Chieh Chan, Wei-Ming Chang, Yuan-Feng Lin, Chih-Jen Yang, Chia-Yu Su, Ming-Shyan Huang, Alexander T H Wu, Michael Hsiao
Distant metastasis and recurrence are the greatest challenges in the clinical management of lung cancer. Despite advances in targeted therapies, high mortality rates persist. Therefore, alternative therapeutic interventions are urgently required. Accumulating evidence indicates that normalizing tumor metabolism may be a way to increase therapeutic efficacy and to reduce tumor malignancy. Here, we analyzed integrated transcriptomics data and an shRNA library against glycolytic enzymes and found that elevated Aldolase A expression is highly correlated with metastatic potential and a poor prognosis in patients with non-small cell lung cancer (NSCLC)...
June 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28607591/pet-of-her2-expression-with-a-novel-18-fal-labeled-affibody
#14
Yuping Xu, Zhicheng Bai, Qianhuan Huang, Yunyun Pan, Donghui Pan, Lizhen Wang, Junjie Yan, Xinyu Wang, Runlin Yang, Min Yang
Background: Human epidermal growth factor receptor type 2 (HER2) is abundant in a wide variety of tumors and associated with the poor prognosis. Radiolabeled affibodies are potential candidates for detecting HER2-positive lesions. However, laborious multiple-step synthetic procedure and high abdomen background may hinder the widespread use. Herein, cysteinylated ZHER2:342 modified with a new hydrophilic linker (denoted as MZHER2:342) was designed and labeled using (18)FAl-NOTA strategies. The biologic efficacy of the novel tracer and its feasibilities for in vivo monitoring HER2 levels were also investigated in xenograft models with different HER2 expressions...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28602974/fzd8-a-target-of-p53-promotes-bone-metastasis-in-prostate-cancer-by-activating-canonical-wnt-%C3%AE-catenin-signaling
#15
Qiji Li, Liping Ye, Zhang Xin, Min Wang, Chuyong Lin, Shuai Huang, Wei Guo, Yingrong Lai, Hong Du, Jun Li, Libing Song, Xinsheng Peng
Prostate cancer (PCa) is the second most frequently diagnosed cancer among men and exhibits a high propensity to metastasize to bone. Currently, bone metastasis remains incurable, and therapies are limited. A better understanding of the molecular mechanisms involved in PCa bone metastasis is needed to develop more effective therapeutics for this disease. Herein, we reported that among the FZD family, FZD8 was robustly upregulated in bone-metastastic PCa cell lines and tissues. High levels of FZD8 expression were significantly positively associated with clinical tumor progression and bone metastasis...
June 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28599493/blueberries-inhibit-cyclooxygenase-1-and-cyclooxygenase-2-activity-in-human-epithelial-ovarian-cancer
#16
Wumei Lin, Zhigang Li
Ovarian cancer (OC) is the sixth and eighth leading cause of cancer mortality among women in developed and developing countries, respectively. Medical therapy is the main method for the treatment of OC. However, drug toxicity and the marked side effects of chemotherapy limit the usage and therapeutic results of the treatments. Therefore, the identification of multi-target agents with few side effects and high effectiveness is required. Traditional Chinese medicine has been used clinically to treat various types of cancer for thousands of years and is considered to possess multiple components and agents, which exert efficient therapeutic functions with few side effects...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28599478/microrna-375-suppresses-esophageal-cancer-cell-growth-and-invasion-by-repressing-metadherin-expression
#17
Changmei Hu, Liang Lv, Jie Peng, Deliang Liu, Xuehong Wang, Yuqian Zhou, Jirong Huo
Accumulating evidence indicates that aberrant expression of microRNAs is involved in tumorigenesis, tumor progression and response to therapy. MicroRNA-375 (miR-375) is an important cancer-associated RNA that is downregulated in multiple types of cancer. In the present study, the potential effects of and underlying molecular mechanism for miR-375 in esophageal cancer were investigated. The expression of miR-375 in paired esophageal squamous cell carcinoma (ESCC) and non-tumor tissues from 10 patients was quantified using the reverse transcription-quantitative polymerase chain reaction...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28596501/identification-and-validation-long-non-coding-rnas-of-oral-squamous-cell-carcinoma-by-bioinformatics-method
#18
Meng Yang, Xingliang Xiong, Longcong Chen, Li Yang, Xian Li
Gene markers of oral squamous cell carcinoma (OSCC) have great significance on early diagnosis and treatment of clinical oral cancer. In this study, we used RNA-Seq data from OSCC patients and filtered differentially-expressed long non-coding RNA (lncRNA) to further clarify the molecular mechanism. Firstly, we downloaded datasets of OSCC from National Center for Biotechnology Information(NCBI), which were predicted and analyzed by cufflinks and tophat. Then, differentially expressed lncRNA enrichment was performed with The Database for Annotation, Visualization and Integrated Discovery (DAVID)...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588694/high-level-of-calpain1-promotes-cancer-cell-invasion-and-migration-in-oral-squamous-cell-carcinoma
#19
Da Ma, Juan Fang, Ying Liu, Jing-Jing Song, Yan-Qiong Wang, Juan Xia, Bin Cheng, Zhi Wang
Calpain1, termed conventional calpain and a member of the Ca(2+)-dependent neutral cysteine proteases, is considered to be involved in cancer formation and development. However, the effect of calpain1 on oral squamous cell carcinoma (OSCC) remains poorly understood. The aim of the present study was to evaluate the possibility of calpain1 as a potential molecular target for OSCC diagnosis and therapy. The present study demonstrates that calpain1 was overexpressed in OSCC cell lines and 4/7 of the tumor tissues in paired samples of tumor and noncancerous matched tissues (NCMT)...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28586114/a-phosphokinome-based-screen-uncovers-new-drug-synergies-for-cancer-driven-by-liver-specific-gain-of-non-oncogenic-rtks
#20
Yannan Fan, Maria Arechederra, Sylvie Richelme, Fabrice Daian, Chiara Novello, Julien Calderaro, Luca Di Tommaso, Guillaume Morcrette, Sandra Rebouissou, Matteo Donadon, Emanuela Morenghi, Jessica Zucman-Rossi, Massimo Roncalli, Rosanna Dono, Flavio Maina
Genetic mutations leading to oncogenic variants of receptor tyrosine kinases (RTKs) are frequent events during tumorigenesis; however, the cellular vulnerability to non-oncogenic RTK fluctuations has not been characterized. Here, we demonstrated genetically that liver subtle increases in wild-type Met RTK levels are sufficient for spontaneous tumors in mice (Alb-R26(Met) ), conceptually illustrating how the shift from physiological to pathological conditions results from slight perturbations in signaling dosage...
June 6, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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