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Targeted cancer therapy molecular level

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https://www.readbyqxmd.com/read/28212901/the-dissociation-of-the-hsp60-pro-caspase-3-complex-by-bis-pyridyl-oxadiazole-copper-complex-cubipyoxa-leads-to-cell-death-in-nci-h292-cancer-cells
#1
Celeste Caruso Bavisotto, Dragana Nikolic, Antonella Marino Gammazza, Rosario Barone, Filippa Lo Cascio, Emanuele Mocciaro, Giovanni Zummo, Everly Conway de Macario, Alberto Jl Macario, Francesco Cappello, Valentina Giacalone, Andrea Pace, Giampaolo Barone, Antonio Palumbo Piccionello, Claudia Campanella
Cell survival and proliferation are central to carcinogenesis, involving various mechanisms among which those that impede apoptosis are important. In this, the role of the molecular chaperone Hsp60 is unclear since it has been reported that it can be both, pro- or anti-apoptotic. A solution to this riddle is crucial to the development of anti-cancer therapies targeting Hsp60. We addressed this question using a tumor cell line, NCI-H292, and [Cu(3,5-bis(2'-pyridyl)-1,2,4-oxadiazole)2(H2O)2](ClO4)2, CubipyOXA, a copper-containing compound with cytotoxic properties...
February 10, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28211800/upregulated-mir-483-5p-expression-as-a-prognostic-biomarker-for-esophageal-squamous-cell-carcinoma
#2
Liying Xue, Jinglong Nan, Li Dong, Cuiying Zhang, Hui Li, Rentura Na, Huijie He, Yadi Wang
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common cause of cancer-associated mortality. Uncovering novel molecular biomarkers that can predict ESCC development will improve personalized therapy. OBJECTIVE: The goal of the current study was to investigate the expression pattern of miR-483-5p and determine its prognostic value in ESCC. METHODS: We first analyzed miRNA-seq data obtained from the Cancer Genome Atlas (TCGA) cohort to evaluate the prognostic value of miR-483-5p in ESCC...
February 3, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28208987/bcl6-mrna-expression-level-in-invasive-duct-carcinoma-not-otherwise-specified
#3
Eman Badr, Eman Masoud, Asmaa Gaber Abdou, Marwa Serag Eldien
INTRODUCTION: B-Cell Lymphoma 6 (BCL6) has an oncogenic role in tumourigenesis of various malignancies. It represses genes involved in terminal differentiation and plays complementary role with Signal Transducer and Activator of Transcription 3 (STAT3) in triple-negative breast cancer cellular function. AIM: To evaluate the expression of BCL6 in cancer breast and determine its correlation with the clinico-pathological features including the molecular subtype of breast carcinoma...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28208828/ginkgolic-acid-c-17-1-derived-from-ginkgo-biloba-leaves-suppresses-constitutive-and-inducible-stat3-activation-through-induction-of-pten-and-shp-1-tyrosine-phosphatase
#4
Seung Ho Baek, Jong Hyun Lee, Chulwon Kim, Jeong-Hyeon Ko, Seung-Hee Ryu, Seok-Geun Lee, Woong Mo Yang, Jae-Young Um, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Gautam Sethi, Kwang Seok Ahn
Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that regulates various critical functions involved in progression of diverse hematological malignancies, including multiple myeloma, therefore attenuating STAT3 activation may have a potential in cancer therapy...
February 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28207159/the-critical-role-of-the-znf217-oncogene-in-promoting-breast-cancer-metastasis-to-the-bone
#5
Aurélie Bellanger, Caterina F Donini, Julie A Vendrell, Jonathan Lavaud, Irma Machuca-Gayet, Maëva Ruel, Julien Vollaire, Evelyne Grisard, Balázs Győrffy, Ivan Bièche, Olivier Peyruchaud, Jean-Luc Coll, Isabelle Treilleux, Véronique Maguer-Satta, Véronique Josserand, Pascale A Cohen
Bone metastasis affects more than 70% of patients with advanced breast cancer. However, the molecular mechanisms underlying this process remain unclear. Based on the analysis of clinical datasets, and in vitro and in vivo experiments, we report that the ZNF217 oncogene is a crucial mediator and indicator of bone metastasis. Patients with high ZNF217 mRNA expression levels in primary breast tumours had a higher risk of developing bone metastases. MDA-MB-231 breast cancer cells stably transfected with ZNF217 (MDA-MB-231-ZNF217) displayed the dysregulated expression of a set of genes with bone homing and metastasis characteristics, which overlapped with two previously described "osteolytic bone metastasis" gene signatures, while also highlighting the bone morphogenetic protein (BMP) pathway...
February 16, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28205537/her2-alterations-in-muscle-invasive-bladder-cancer-patient-selection-beyond-protein-expression-for-targeted-therapy
#6
Bernhard Kiss, Alexander W Wyatt, James Douglas, Veronika Skuginna, Fan Mo, Shawn Anderson, Diana Rotzer, Achim Fleischmann, Vera Genitsch, Tetsutaro Hayashi, Maja Neuenschwander, Christine Buerki, Elai Davicioni, Colin Collins, George N Thalmann, Peter C Black, Roland Seiler
Although the introduction of novel targeted agents has improved patient outcomes in several human cancers, no such advance has been achieved in muscle-invasive bladder cancer (MIBC). However, recent sequencing efforts have begun to dissect the complex genomic landscape of MIBC, revealing distinct molecular subtypes and offering hope for implementation of targeted therapies. Her2 (ERBB2) is one of the most established therapeutic targets in breast and gastric cancer but agents targeting Her2 have not yet demonstrated anti-tumor activity in MIBC...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193222/phosphorylation-dependent-regulation-of-aldh1a1-by-aurora-kinase-a-insights-on-their-synergistic-relationship-in-pancreatic-cancer
#7
Jing Wang, Kumar Nikhil, Keith Viccaro, Lei Chang, Jacoba White, Kavita Shah
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) formation are key underlying causes that promote extensive metastasis, drug resistance, and tumor recurrence in highly lethal pancreatic cancer. The mechanisms leading to EMT and CSC phenotypes are not fully understood, which has hindered the development of effective targeted therapies capable of improving treatment outcomes in patients with pancreatic cancer. RESULTS: We show a central role of Aurora kinase A (AURKA) in promoting EMT and CSC phenotypes via ALDH1A1, which was discovered as its direct substrate using an innovative chemical genetic screen...
February 13, 2017: BMC Biology
https://www.readbyqxmd.com/read/28192747/biology-and-patterns-of-response-to-egfr-inhibition-in-squamous-cell-cancers-of-the-lung-and-head-neck
#8
REVIEW
Rosalyn A Juergens, Scott V Bratman, Ming-Sound Tsao, Scott A Laurie, M Sara Kuruvilla, Albiruni R A Razak, Aaron R Hansen
The identification of common molecular aberrations that drive cancer progression has led to targeted therapies that improve treatment efficacy in many tumor types. Epidermal growth factor receptor (EGFR) inhibitors have been used to treat both lung and head and neck cancers with squamous cell histology. These tumors often show high EGFR expression and/or increased gene copy number, but low incidence of the activating kinase domain mutations common to adenocarcinomas of the lung. In this manuscript, we review clinical trial data on EGFR-inhibitors in the treatment of squamous cell carcinoma (SqCC) of the lung and head and neck (SCCHN), including both efficacy and biomarker analyses...
January 17, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28187748/characterization-of-ovarian-clear-cell-carcinoma-using-target-drug-based-molecular-biomarkers-implications-for-personalized-cancer-therapy
#9
Mengjiao Li, Haoran Li, Fei Liu, Rui Bi, Xiaoyu Tu, Lihua Chen, Shuang Ye, Xi Cheng
BACKGROUND: It has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC)...
February 10, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28186090/downregulation-of-microrna-145-promotes-epithelial-mesenchymal-transition-via-regulating-snail-in-osteosarcoma
#10
Z Zhang, M Zhang, Q Chen, Q Zhang
Metastasis is the principal cause of cancer death and occurs through multiple, complex processes. Epithelial to mesenchymal transition (EMT) is an important process during embryonic development and has also been hypothesized to exhibit a significant role in cancer cell invasion and metastasis. MicroRNAs (miRNAs) are a class of widespread noncoding RNAs. In recent years, many studies have shown that miRNAs could influence the signaling pathways and downstream events that define EMT on a molecular level. However, the exact role and mechanisms of miR-145 in EMT of osteosarcoma (OS) was unknown...
February 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28185938/folate-targeted-nanoparticle-delivery-of-androgen-receptor-shrna-enhances-the-sensitivity-of-hormone-independent-prostate-cancer-to-radiotherapy
#11
Xinjun Zhang, Nianli Liu, ZhiYing Shao, Hui Qiu, Hong Yao, JiaYin Ji, Jianshe Wang, Wenchao Lu, Ronald C Chen, Longzhen Zhang
Androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer (PCa). PCa patients typically receive androgen deprivation therapy; nonetheless, these patients eventually develop castration and radiation resistance. We hypothesized that we could further improve radiotherapeutic efficacy of hormone-independent PCa (HIPC) by silencing AR. In this study, nanoparticle (NP) AR-shRNA was formulated using folate-targeted H1 nanopolymer. We demonstrated that NP AR-shRNA enhances PCa radiosensitivity as indicated by the inhibition of cell growth, increased apoptosis, and increased cell cycle arrest in AR-dependent HIPC in vitro...
February 6, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28185165/oncolytic-viruses-emerging-options-for-the-treatment-of-breast-cancer
#12
REVIEW
Yogesh R Suryawanshi, Tiantian Zhang, Karim Essani
Breast cancer (BC) is the most common type of cancer among women and is the second most common cause of cancer-related deaths, following lung cancer. Severe toxicity associated with a long-term use of BC chemo- and radiotherapy makes it essential to look for newer therapeutics. Additionally, molecular heterogeneity at both intratumoral and intertumoral levels among BC subtypes is known to result in a differential response to standard therapeutics. Oncolytic viruses (OVs) have emerged as one of the most promising treatment options for BC...
March 2017: Medical Oncology
https://www.readbyqxmd.com/read/28183249/adiponectin-as-a-potential-therapeutic-target-for-prostate-cancer
#13
Hanuma Kumar Karnati, Manas Kumar Panigrahi, Yazhou Li, David Tweedie, Nigel H Greig
Adipokines are bioactive proteins that mediate proliferation, metabolism, inflammation, and angiogenesis. Adiponectin is an important adipokine that exerts multiple key functions via its anti-metabolic syndrome and anti-inflammatory properties. A number of adiponectin receptors, AdipoR1, AdipoR2 and T-cadherin, have been identified. Recent studies have suggested the involvement of adiponectin and receptors in several cancers, including prostate, breast, endometrial, brain, and colon cancer. Altered levels of adiponectin expression, or its interacting receptors, in cancers can lead to dysregulation of signaling pathways...
February 8, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28181105/protein-kinase-ck2-is-important-for-the-function-of-glioblastoma-brain-tumor-initiating-cells
#14
Amber L Rowse, Sara A Gibson, Gordon P Meares, Rajani Rajbhandari, Susan E Nozell, Kory J Dees, Anita B Hjelmeland, Braden C McFarland, Etty N Benveniste
Protein kinase CK2 is a ubiquitously expressed serine/threonine kinase composed of two catalytic subunits (α) and/or (α') and two regulatory (β) subunits. The expression and kinase activity of CK2 is elevated in many different cancers, including glioblastoma (GBM). Brain tumor initiating cells (BTICs) are a subset of cells that are highly tumorigenic and promote the resistance of GBM to current therapies. We previously reported that CK2 activity promotes prosurvival signaling in GBM. In this study, the role of CK2 signaling in BTIC function was examined...
February 8, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28160548/regulation-of-mirna-29c-and-its-downstream-pathways-in-preneoplastic-progression-of-triple-negative-breast-cancer
#15
Anjana Bhardwaj, Harpreet Singh, Kimal Rajapakshe, Kazunoshin Tachibana, Nivetha Ganesan, Yinghong Pan, Preethi H Gunaratne, Cristian Coarfa, Isabelle Bedrosian
Little is understood about the early molecular drivers of triple-negative breast cancer (TNBC), making the identification of women at risk and development of targeted therapy for prevention significant challenges. By sequencing a TNBC cell line-based breast cancer progression model we have found that miRNA-29c is progressively lost during TNBC tumorigenesis. In support of the tumor suppressive role of miRNA 29c, we found that low levels predict poor overall patient survival and, conversely, that ectopic expression of miRNA-29c in preneoplastic cell models inhibits growth...
January 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28160423/polymeric-delivery-of-sirna-against-integrin-%C3%AE-1-cd29-to-reduce-attachment-and-migration-of-breast-cancer-cells
#16
Daniel Nisakar Meenakshi Sundaram, Cezary Kucharski, Manoj B Parmar, Remant Bahadur Kc, Hasan Uludağ
Cell surface integrins, which play important roles in the survival, proliferation, migration, and invasion of cancer cells, are a viable target for treatment of metastatic breast cancer. This line of therapy still remains challenging due to the lack of proper identification and validation of effective targets as well as the lack of suitable therapeutic agents for treatment. The focus is on one such molecular target for this purpose, namely integrin-β1, and effective lowering of integrin-β1 levels on a breast cancer model (MDA-MB-231 cells) is achieved by delivering a dicer-substrate short interfering RNA (siRNA) targeting integrin-β1 with lipid-modified low molecular weight polyethylenimine polymers...
February 3, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28160046/eag1-voltage-dependent-potassium-channels-structure-electrophysiological-characteristics-and-function-in-cancer
#17
REVIEW
Xuzhao Wang, Yafei Chen, Yuhong Zhang, Shuai Guo, Li Mo, Hailong An, Yong Zhan
Eag1 (ether-à-go-go-1), a member of the voltage-dependent potassium channel family, is expressed mainly in the brain, and at low levels in placenta, testis, and adrenal gland, and only transiently in myoblasts. Recently, several studies have suggested that Eag1 is selectively expressed in various tumor tissues. Eag1 plays important roles in tumor proliferation, malignant transformation, invasion, metastasis, recurrence, and prognosis. Therefore, it has become a new molecular target for tumor diagnosis, prognosis evaluation, and tumor-targeted therapy...
February 3, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28158983/cd73-nt5e-is-a-target-of-mir-30a-5p-and-plays-an-important-role-in-the-pathogenesis-of-non-small-cell-lung-cancer
#18
Jianjie Zhu, Yuanyuan Zeng, Wei Li, Hualong Qin, Zhe Lei, Dan Shen, Dongmei Gu, Jian-An Huang, Zeyi Liu
BACKGROUND: CD73 (ecto-5'-nucleotidase) is implicated in the development of many types of cancer. CD73 inhibitors are currently being tested in clinical trials for the treatment of cancer. Understanding the molecular and cellular actions of CD73 inhibitors is the key to improving this line of therapy. METHODS: Quantitative real-time PCR (qRT-PCR) was used to detect the expression of CD73 and miR-30a-5p; Western blot and immunohistochemical assays were used to investigate the levels of CD73 and other proteins...
February 3, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28149768/metastatic-lung-cancer-in-the-age-of-targeted-therapy-improving-long-term-survival
#19
COMMENT
Jaydira Del Rivero, Lindsey Enewold, Anish Thomas
Epidermal growth factor receptor (EGFR) mutations are the most frequent targetable genetic abnormality observed in non-small cell lung cancer (NSCLC). More than a decade after EGFR mutations were shown to predict sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKI), retrospective cohort studies are now identifying and characterizing 5-year survivors. While these studies indicate subsets of patients achieving long-term survival, there is paucity of data pertaining to the long-term survival benefits of these targeted therapies at a population level...
December 2016: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28149332/the-immunomodulatory-anticancer-agent-rrx-001-induces-an-interferon-response-through-epigenetic-induction-of-viral-mimicry
#20
Hongjuan Zhao, Shoucheng Ning, Rosalie Nolley, Jan Scicinski, Bryan Oronsky, Susan J Knox, Donna M Peehl
BACKGROUND: RRx-001, a dinitroazetidine derivative, is a novel anticancer agent currently in phase II clinical trials. It mediates immunomodulatory effects either directly through polarization of tumor associated macrophages or indirectly through vascular normalization and increased T-lymphocyte infiltration. With multiple additional mechanisms of action including upregulation of oxidative stress, depletion of GSH and NADPH, anti-angiogenesis and epigenetic modulation, RRx-001 is being studied as a radio- and chemo-sensitizer to resensitize tumors to prior therapy and to prime tumors to respond to radiation, chemotherapy and immunotherapy in combination therapy studies...
2017: Clinical Epigenetics
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