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Targeted cancer therapy

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https://www.readbyqxmd.com/read/28538837/microrna-455-suppresses-the-oncogenic-function-of-hdac2-in-human-colorectal-cancer
#1
Q D Mao, W Zhang, K Zhao, B Cao, H Yuan, L Z Wei, M Q Song, X S Liu
Colorectal cancer (CRC) is the fourth leading cause of cancer-induced mortality. Histone deacetylase 2 (HDAC2) is involved in prognosis and therapy of CRC. This study aimed to explore novel therapeutic targets for CRC. The alteration of HDAC2 expression in CRC tissues was estimated by qRT-PCR. After lentivirus transfection, HDAC2 knockdown was confirmed by western blot analysis. The effect of HDAC2 knockdown on cell proliferation was then assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay...
May 18, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28538671/engineering-exosomes-for-cancer-therapy
#2
REVIEW
Katie E Gilligan, Róisín M Dwyer
There remains an urgent need for novel therapeutic strategies to treat metastatic cancer, which results in over 8 million deaths annually worldwide. Following secretion, exosomes are naturally taken up by cells, and capable of the stable transfer of drugs, therapeutic microRNAs and proteins. As knowledge of the biogenesis, release and uptake of exosomes continues to evolve, and thus also has interest in these extracellular vesicles as potential tumor-targeted vehicles for cancer therapy. The ability to engineer exosome content and migratory itinerary holds tremendous promise...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538431/immunotherapy-for-lung-cancer-targeting-the-pd-1-pathway
#3
Sam Vafadar
Lung cancer is the third most common cancer in the United States and the top cause of cancer-related mortality in men and women. Despite advances in chemotherapy, molecular therapies, and CT screening, overall survival remains dismal. Additional options and a new treatment paradigm are needed. This article focuses on immunotherapy, a promising new approach targeted at the PD-1 inhibition pathway.
June 2017: JAAPA: Official Journal of the American Academy of Physician Assistants
https://www.readbyqxmd.com/read/28538184/taxane-platin-resistant-lung-cancers-co-develop-hypersensitivity-to-jumonjic-demethylase-inhibitors
#4
Maithili P Dalvi, Lei Wang, Rui Zhong, Rahul K Kollipara, Hyunsil Park, Juan Bayo, Paul Yenerall, Yunyun Zhou, Brenda C Timmons, Jaime Rodriguez-Canales, Carmen Behrens, Barbara Mino, Pamela Villalobos, Edwin R Parra, Milind Suraokar, Apar Pataer, Stephen G Swisher, Neda Kalhor, Natarajan V Bhanu, Benjamin A Garcia, John V Heymach, Kevin Coombes, Yang Xie, Luc Girard, Adi F Gazdar, Ralf Kittler, Ignacio I Wistuba, John D Minna, Elisabeth D Martinez
Although non-small cell lung cancer (NSCLC) patients benefit from standard taxane-platin chemotherapy, many relapse, developing drug resistance. We established preclinical taxane-platin-chemoresistance models and identified a 35-gene resistance signature, which was associated with poor recurrence-free survival in neoadjuvant-treated NSCLC patients and included upregulation of the JumonjiC lysine demethylase KDM3B. In fact, multi-drug-resistant cells progressively increased the expression of many JumonjiC demethylases, had altered histone methylation, and, importantly, showed hypersensitivity to JumonjiC inhibitors in vitro and in vivo...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537989/obesity-is-independently-associated-with-increased-risk-of-hepatocellular-cancer-related-mortality-a-systematic-review-and-meta-analysis
#5
Arjun Gupta, Avash Das, Kaustav Majumder, Nivedita Arora, Helen G Mayo, Preet P Singh, Muhammad S Beg, Siddharth Singh
OBJECTIVE: Excess body weight is associated with increased risk of developing hepatocellular cancer (HCC), but its effect on HCC-related mortality remains unclear. We performed a systematic review and meta-analysis to assess the association between premorbid obesity and HCC-related mortality. MATERIALS AND METHODS: Through a systematic literature search-up to March 2016, we identified 9 observational studies (1,599,453 individuals, 5705 HCC-related deaths) reporting the association between premorbid body mass index (BMI), and HCC-related mortality...
May 23, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28537931/the-network-of-dab2ip-mir-138-in-regulating-drug-resistance-of-renal-cell-carcinoma-associated-with-stem-like-phenotypes
#6
Eun-Jin Yun, Jiancheng Zhou, Chun-Jung Lin, Shan Xu, John Santoyo, Elizabeth Hernandez, Chih-Ho Lai, Ho Lin, Dalin He, Jer-Tsong Hsieh
Targeted therapy is a standard of care for metastatic renal cell carcinoma (RCC) but the response rate is not overwhelmed, which only prolongs a short survival of patients due to the onset of therapeutic resistance. Although the mechanisms are not fully understood, the presence of cancer initiating cells (CIC) may underlie the drug resistance. Nevertheless, identifying CIC phenotypes with its biomarkers in RCC appear to be diverse and controversial from many reports. In this study, we took a different approach to focus on the regulatory mechanism in RCC-CIC and unveil DAB2IP-mediated miR-138 expression that plays a critical role in modulating stem-like phenotypes in RCC via targeting the ABC transporter (ABCA13) as well as oncogenic histone methyltransferase EZH2 while down regulation of miR-138 gene expression in RCC is due to epigenetic gene silencing by DNA methyltransferase 1 (DNMT1)...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537914/epigenomic-study-identifies-a-novel-mesenchyme-homeobox2-gli1-transcription-axis-involved-in-cancer-drug-resistance-overall-survival-and-therapy-prognosis-in-lung-cancer-patients
#7
Leonel Armas-López, Patricia Piña-Sánchez, Oscar Arrieta, Enrique Guzman de Alba, Blanca Ortiz-Quintero, Patricio Santillán-Doherty, David C Christiani, Joaquín Zúñiga, Federico Ávila-Moreno
Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537894/intratumoral-depletion-of-regulatory-t-cells-using-cd25-targeted-photodynamic-therapy-in-a-mouse-melanoma-model-induces-antitumoral-immune-responses
#8
Dong Sun Oh, Heegon Kim, Ji Eun Oh, Hi Eun Jung, Yun Soo Lee, Ji-Ho Park, Heung Kyu Lee
Tumor immunotherapy aims to overcome the immunosuppressive microenvironment within tumors, and various approaches have been developed. Tumor-associated T regulatory cells (Tregs) suppress the activation and expansion of tumor antigen-specific effector T cells, thus, providing a permissive environment for tumor growth. Therefore, optimal strategies need to be established to deplete tumor-infiltrated Tregs because systemic depletion of Tregs can result in reduced anti-tumor effector cells and autoimmunity. Here, to selectively deplete Tregs in tumors, we intratumorally injected anti-CD25 antibodies conjugated to Chlorin e6 (Ce6), a photosensitizer that absorbs light to generate reactive oxygen species...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537885/identifying-cpg-sites-with-different-differential-methylation-frequencies-in-colorectal-cancer-tissues-based-on-individualized-differential-methylation-analysis
#9
Haidan Yan, Jun He, Qingzhou Guan, Hao Cai, Lin Zhang, Weicheng Zheng, Lishuang Qi, Suyun Zhang, Huaping Liu, Hongdong Li, Wenyuan Zhao, Sheng Yang, Zheng Guo
A big challenge to clinical diagnosis and therapy of colorectal cancer (CRC) is its extreme heterogeneity, and thus it would be of special importance if we could find common biomarkers besides subtype-specific biomarkers for CRC. Here, with DNA methylation data produced by different laboratories, we firstly revealed that the relative methylation-level orderings (RMOs) of CpG sites within colorectal normal tissues are highly stable but widely disrupted in the CRC tissues. This finding provides the basis for using the RankComp algorithm to identify differentially methylated (DM) CpG sites in every individual CRC sample through comparing the RMOs within the individual sample with the stable RMOs predetermined in normal tissues...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537878/biological-characterization-of-sn32976-a-selective-inhibitor-of-pi3k-and-mtor-with-preferential-activity-to-pi3k%C3%AE-in-comparison-to-established-pan-pi3k-inhibitors
#10
Gordon W Rewcastle, Sharada Kolekar, Christina M Buchanan, Swarna A Gamage, Anna C Giddens, Kit Y Tsang, Jackie D Kendall, Ripudaman Singh, Woo-Jeong Lee, Greg C Smith, Weiping Han, David J Matthews, William A Denny, Peter R Shepherd, Stephen M F Jamieson
Multiple therapeutic agents have been developed to target the phosphatidylinositol 3-kinase (PI3K) signaling pathway, which is frequently dysregulated in cancer promoting tumor growth and survival. These include pan PI3K inhibitors, which target class Ia PI3K isoforms and have largely shown limited single agent activity with narrow therapeutic windows in clinical trials. Here, we characterize SN32976, a novel pan PI3K inhibitor, for its biochemical potency against PI3K isoforms and mTOR, kinase selectivity, cellular activity, pharmacokinetics, pharmacodynamics and antitumor efficacy relative to five clinically-evaluated pan PI3K inhibitors: buparlisib, dactolisib, pictilisib, omipalisib and ZSTK474...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537788/the-precision-of-hepatic-arterial-infusion-scintigraphy-as-a-quantitative-biomarker-of-tumor-microvasculature
#11
Mark Dunphy, Neeta Pandit-Taskar, Josef J Fox, Nancy Kemeny
OBJECTIVE: Optimal clinical development of new cancer therapies targeting tumor vasculature requires new target-specific response assays. This clinical study examined the test-retest repeatability of SPECT as an in vivo assay of angiogenic hepatic tumor microvasculature using an intraarterial infusion of (99m)Tc-macroaggregated albumin (MAA) delivered via a hepatic artery infusion (HAI) pump. MATERIALS AND METHODS: Patients with primary or secondary cancerous liver tumors with HAI pump-catheter implants placed for HAI chemotherapy underwent hepatic SPECT after separate arterial infusions of 37 and 185 MBq of (99m)Tc-MAA via an HAI pump...
May 24, 2017: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/28537761/correlation-analysis-of-18-f-fluorodeoxyglucose-and-18-f-fluoroazomycin-arabinoside-uptake-distributions-in-lung-tumours-during-radiation-therapy
#12
Dario Di Perri, John A Lee, Anne Bol, François-Xavier Hanin, Guillaume Janssens, Daniel Labar, Annie Robert, Edmond Sterpin, Xavier Geets
BACKGROUND: PET-guided dose painting (DP) aims to target radioresistant tumour regions in order to improve radiotherapy (RT) outcome. Besides the well-known [(18)F]fluorodeoxyglucose (FDG), the hypoxia positron emission tomography (PET) tracer [(18)F]fluoroazomycin arabinoside (FAZA) could provide further useful information to guide the radiation dose prescription. In this study, we compare the spatial distributions of FDG and FAZA PET uptakes in lung tumours. MATERIAL AND METHODS: Fourteen patients with unresectable lung cancer underwent FDG and FAZA 4D-PET/CT on consecutive days at three time-points: prior to RT (pre), and during the second (w2), and the third (w3) weeks of RT...
May 24, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28535626/-expression-and-prognostic-significance-of-microenvironment-related-prognostic-factors-in-patients-with-classical-hodgkin-s-lymphoma
#13
T T Wang, S X Li, B Xia, H F Zhao, W Xu, H L Yang, X F Wang, Y Yu, B C Sun, Y Z Zhang
Objective: To observe the expression of three microenvironment related prognostic factors, i. e. programmed death 1 (PD-1), forkhead box protein 3(FOXP3) and colony-stimulating factor 1 receptor(CSF-1R) protein in classical Hodgkin's lymphoma (CHL) patients, and to explore the correlation between the protein expression and the prognosis of the patients. Methods: A total of 45 cases of CHL patients, who had been admitted to the Tianjin Medical University Cancer Institute and Hospital and Chinese PLA General Hospital from February 2005 to August 2010 were analyzed, including clinical features, prognostic factors, and treatment regimens...
May 16, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28535533/malat1-modulates-tgf-%C3%AE-1-induced-endothelial-to-mesenchymal-transition-through-downregulation-of-mir-145
#14
Yin Xiang, Yachen Zhang, Yong Tang, Qianhui Li
BACKGROUND/AIMS: Endothelial-to-mesenchymal transition (EndMT) plays significant roles under various pathological conditions including cardiovascular diseases, fibrosis, and cancer. EndMT of endothelial progenitor cells (EPCs) contributes to neointimal hyperplasia following cell therapy Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that promotes metastasis and cancer. MicroRNA-145 (miR-145) is a tumor suppressor that has been reported to inhibit SMAD3-mediated epithelial-to-mesenchymal transition (EMT) of cancer cells...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28535014/mir-455-inhibits-cell-proliferation-and-migration-via-negative-regulation-of-egfr-in-human-gastric-cancer
#15
Tao Ning, Zhijuan Peng, Shuang Li, Yanjun Qu, Haiyang Zhang, Jingjing Duan, Xinyi Wang, Haiou Yang, Rui Liu, Ting Deng, Ming Bai, Yi Wang, Yiran Si, Le Zhang, Xia Wang, Shaohua Ge, Likun Zhou, Guoguang Ying, Yi Ba
Epidermal growth factor receptor (EGFR) plays an important role in various types of cancer. However, the therapeutic agents that target EGFR have not produced favorable results in gastric cancer. miRNAs are known to regulate gene expression at the post-transcriptional level. We wondered if miRNAs could be potential therapeutic agents for the targeted therapy against EGFR. In this study, we found an increase in the copies of EGFR mRNA and the upregulated expression of the EGFR protein in gastric cancer tissues compared with normal gastric tissues...
May 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28535010/microrna%C3%A2-141-inhibits-the-self%C3%A2-renewal-of-glioblastoma-stem-cells-via-jagged1
#16
Xianfeng Gao, Xiaobo Zhu, Yang Sun, Jingwei Liu
Glioblastoma multiforme is one of the most lethal types of brain cancer. With limited success from conventional therapies, the cancer stem cell theory was developed, and investigation into microRNAs (miRs) has facilitated understanding of this theory. The present study demonstrated that miR‑141 is suppressed in sorted cluster of differentiation (CD) 133(+) glioblastoma stem cells (GSCs) compared with CD133(‑) non‑glioblastoma stem cells (NSCs) from patient samples. In addition, miR‑141 overexpression inhibited the sphere formation ability of GSCs in vitro and in vivo...
May 17, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28535002/hsa-mir-485-5p-reverses-epithelial-to-mesenchymal-transition-and-promotes-cisplatin-induced-cell-death-by-targeting-pak1-in-oral-tongue-squamous-cell-carcinoma
#17
Xiu-Juan Lin, Chang-Li He, Ting Sun, Xue-Jing Duan, Yi Sun, Shi-Jiang Xiong
Oral squamous cell carcinoma (OSCC) is currently a highly prevalent disease worldwide. Cisplatin (CDDP) is widely used for the chemotherapy of OSCC. Yet, the molecular mechanisms responsible for cisplatin resistance have not been fully elucidated. In this study, we showed that overexpression of p21 (RAC1) activated kinase 1 (PAK1) induced epithelial to mesenchymal transition (EMT) and significantly promoted the invasion and migration of oral squamous cell carcinoma SCC25 cells. Emerging evidence indicates a strong link between resistance to therapy and the induction of EMT in cancer...
May 16, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28534999/mir-370-regulates-cell-proliferation-and-migration-by-targeting-egfr-in-gastric-cancer
#18
Tao Ning, Haiyang Zhang, Xinyi Wang, Shuang Li, Le Zhang, Ting Deng, Likun Zhou, Rui Liu, Xia Wang, Ming Bai, Shaohua Ge, Hongli Li, Dingzhi Huang, Guoguang Ying, Yi Ba
Epidermal growth factor receptor (EGFR) is known to be overexpressed in ~30% of gastric cancer (GC) cases, and may serve as an effective biomarker for predicting the clinical benefit of anti-EGFR therapy. However, the mechanism underlying the regulation of EGFR expression remains unknown. Evidence indicates that post-transcriptional regulation may exist in the process of EGFR expression. In the present study, we aimed to explore whether miR-370 is involved in this process, and how it impacts the biological behaviors of GC cells...
May 23, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28534994/amplification-and-the-clinical-significance-of-circulating-cell-free-dna-of-pvt1-in-breast-cancer
#19
Xujing Li, Weijuan Chen, Hui Wang, Qun Wei, Xiaodi Ding, Wentong Li
Duplication in the chromosome 8q24 region is a frequent occurrence in carcinomas. The PVT1 oncogene (PVT1), a long non-coding RNA, is found in this locus. PVT1 amplification is a frequent event in cancers, such as in lymphomas, serous ovarian, colorectal and breast cancers. Ectopic PVT1 expression is related with reduced survival duration in cancer patients. in the present study, we proved that PVT1 is markedly augmented in breast cancer tissues compared with adjacent non-tumorous tissues. Thus, PVT1 is an independent prognostic factor for the survival duration of breast cancer patients...
May 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28534964/tamoxifen-promotes-apoptosis-and-inhibits-invasion-in-estrogen%C3%A2-positive-breast-cancer-mcf%C3%A2-7-cells
#20
Wei Li, Xingpeng Shi, Yan Xu, Jianmei Wan, Shaohua Wei, Ran Zhu
Tamoxifen (TAM) is the earliest non-steroidal antiestrogen drug, which has been widely used in endocrine therapy targeting breast cancer. The aim of the present study was to investigate the effect of TAM on the proliferation, apoptosis, migration and invasion of the estrogen‑positive (ER+) breast cancer cell line MCF‑7 in vitro, and elucidate its mechanisms. It was demonstrated that TAM suppressed proliferation, migration and invasion, and induced apoptosis in MCF‑7 cells. Further investigation revealed that the mitochondrial membrane potential and the amount of ATP were significantly decreased following the treatment of MCF‑7 cells with TAM...
May 18, 2017: Molecular Medicine Reports
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