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Angiogenesis and cancer therapy

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https://www.readbyqxmd.com/read/28446055/investigational-drugs-for-nasopharyngeal-carcinoma
#1
Brigette B Y Ma, Edwin P Hui, Anthony T C Chan
Nasopharyngeal carcinoma (NPC) is endemic to Southern China and Asia and is etiologically associated with the Epstein Barr virus (EBV). Whole exome and genome sequencing (WES, WGS) studies of NPC have reported several actionable therapeutic targets, and that the mutational load of NPC maybe comparable to that of squamous head and neck cancer. These unique biological characteristics have been exploited as potential targets and a wide range of investigational drugs are being investigated in clinical trials. Area covered: This review focused on the latest clinical development of the most promising classes of investigational agents in the treatment of advanced NPC...
April 27, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28445144/stroma-derived-hgf-drives-metabolic-adaptation-of-colorectal-cancer-to-angiogenesis-inhibitors
#2
Alessia Mira, Virginia Morello, Maria Virtudes Céspedes, Timothy Perera, Paolo M Comoglio, Ramon Mangues, Paolo Michieli
The role of paracrine Hepatocyte Growth Factor (HGF) in the resistance to angiogenesis inhibitors (AIs) is hidden in xenograft models because mouse HGF fails to fully activate human MET. To uncover it, we compared the efficacy of AIs in wild-type and human HGF knock-in SCID mice bearing orthotopic human colorectal tumors. Species-specific HGF/MET signaling dramatically impaired the response to anti-angiogenic agents and boosted metastatic dissemination. In cell-based assays mimicking the consequences of anti-angiogenic therapy, colorectal cancer cells were completely resistant to hypoxia but extremely sensitive to nutrient deprivation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443505/targeted-therapy-of-ovarian-cancer-with-angiogenesis-inhibitors
#3
Ping Duan, Lili Fan, Quansheng Gao, Mukunda Silwal, Mulan Ren, Yang Shen, Wanglei Qu
Specific blocking of interactions between ligands and receptors along the angiogenic pathways represent an effective approach for enhancing the efficacy as well as reducing adverse effects of chemotherapy. Over the past decade, there was a rapid progression in the application of this therapeutic strategy in cancer treatment. Anti-angiogenic therapy is the most promising targeted therapy for ovarian cancer. The addition of bevacizumab to conventional chemotherapy, either in the first-line setting or at disease relapse, may improve overall survival (OS) of ovarian cancer patients, at least in a subset of patients with poor prognosis...
March 28, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28443291/a-review-of-the-development-of-tumor-vasculature-and-its-effects-on-the-tumor-microenvironment
#4
REVIEW
Jake C Forster, Wendy M Harriss-Phillips, Michael Jj Douglass, Eva Bezak
BACKGROUND: The imbalance of angiogenic regulators in tumors drives tumor angiogenesis and causes the vasculature to develop much differently in tumors than in normal tissue. There are several cancer therapy techniques currently being used and developed that target the tumor vasculature for the treatment of solid tumors. This article reviews the aspects of the tumor vasculature that are relevant to most cancer therapies but particularly to vascular targeting techniques. MATERIALS AND METHODS: We conducted a review of identified experiments in which tumors were transplanted into animals to study the development of the tumor vasculature with tumor growth...
2017: Hypoxia
https://www.readbyqxmd.com/read/28440206/role-of-foxm1-in-the-progression-and-epithelial-to-mesenchymal-transition-of-gastrointestinal-cancer
#5
Jing Zhang, Yangyang Niu, Chen Huang
Background and Objective:Gastrointestinal (GI) cancer, characterized by its leading mortality, is one of the most common cancers worldwide. The underlying mechanisms contributing to epithelial to mesenchymal transition (EMT) and metastasis of GI cancer is poorly understood. It is well known that a great number of transcription factors including FoxM1, KLF4, STAT3 and so forth, are associated with the process of EMT and have also been strongly implicated in the proliferation, migration, and invasion of GI cancer cells...
April 24, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28439752/mathematical-modeling-of-cellular-cross-talk-between-endothelial-and-tumor-cells-highlights-counterintuitive-effects-of-vegf-targeted-therapies
#6
Harsh Jain, Trachette Jackson
Tumor growth and progression are critically dependent on the establishment of a vascular support system. This is often accomplished via the expression of pro-angiogenic growth factors, including members of the vascular endothelial growth factor (VEGF) family of ligands. VEGF ligands are overexpressed in a wide variety of solid tumors and therefore have inspired optimism that inhibition of the different axes of the VEGF pathway-alone or in combination-would represent powerful anti-angiogenic therapies for most cancer types...
April 24, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28439492/leptin-signaling-and-cancer-chemoresistance-perspectives
#7
EDITORIAL
Pierre V Candelaria, Antonio Rampoldi, Adriana Harbuzariu, Ruben R Gonzalez-Perez
Obesity is a major health problem and currently is endemic around the world. Obesity is a risk factor for several different types of cancer, significantly promoting cancer incidence, progression, poor prognosis and resistance to anti-cancer therapies. The study of this resistance is critical as development of chemoresistance is a serious drawback for the successful and effective drug-based treatments of cancer. There is increasing evidence that augmented adiposity can impact on chemotherapeutic treatment of cancer and the development of resistance to these treatments, particularly through one of its signature mediators, the adipokine leptin...
April 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28438704/folic-acid-decorated-polyamidoamine-dendrimer-exhibits-high-tumor-uptake-and-sustained-highly-localized-retention-in-solid-tumors-its-utility-for-local-sirna-delivery
#8
Leyuan Xu, W Andrew Yeudall, Hu Yang
The utility of folic acid (FA)-decorated polyamidoamine dendrimer G4 (G4-FA) as a vector was investigated for local delivery of siRNA. In a xenograft HN12 (or HN12-YFP) tumor mouse model of head and neck squamous cell carcinomas (HNSCC), intratumorally (i.t.) injected G4-FA exhibited high tumor uptake and sustained highly localized retention in the tumors according to near infrared (NIR) imaging assessment. siRNA against vascular endothelial growth factor A (siVEGFA) was chosen as a therapeutic modality. Compared to the nontherapeutic treatment groups (PBS solution or dendrimer complexed with nontherapeutic green fluorescent protein siRNA [siGFP]), G4-FA/siVEGFA showed tumor inhibition effects in single-dose and two-dose regimen studies...
April 21, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28437678/efficacy-safety-tolerability-and-price-of-newly-approved-drugs-in-solid-tumors
#9
REVIEW
Tristan A Barnes, Eitan Amir, Arnoud J Templeton, Susana Gomez-Garcia, Beatriz Navarro, Bostjan Seruga, Alberto Ocana
BACKGROUND: New anti-cancer drugs utilize diverse mechanisms of action. Here we evaluate their differential efficacy, safety, tolerability and price. METHODS: Drugs approved for solid tumor treatment between 2000 and 2015 were identified and analyzed in subgroups: agents targeting oncogenes (group 1), anti-angiogenics (group 2), immunotherapy (group 3), and chemotherapy (group 4). Hazard ratios (HRs) were extracted from the registration trials and pooled in a meta-analysis...
April 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28435457/tumor-hypoxia-regulates-forkhead-box-c1-to-promote-lung-cancer-progression
#10
Yu-Jung Lin, Woei-Cherng Shyu, Chi-Wei Chang, Chi-Chung Wang, Chung-Pu Wu, Hsu-Tung Lee, Liang-Jwu Chen, Chia-Hung Hsieh
Forkhead box C1 (FOXC1) is a member of the forkhead family of transcription factors that are characterized by a DNA-binding forkhead domain. Increasing evidence indicates that FOXC1 is involved in tumor progression. However, the role of tumor hypoxia in FOXC1 regulation and its impact on lung cancer progression are unclear. Here, we report that FOXC1 was upregulated in hypoxic areas of lung cancer tissues from rodents or humans. Hypoxic stresses significantly induced FOXC1 expression. Moreover, hypoxia activated FOXC1 transcription via direct binding of hypoxia-inducible factor-1α (HIF-1α) to the hypoxia-responsive element (HRE) in the FOXC1 promoter...
2017: Theranostics
https://www.readbyqxmd.com/read/28433198/tumor-promoting-role-of-anti-tumor-macrophages-in-tumor-microenvironment
#11
REVIEW
Kuntal Kanti Goswami, Tithi Ghosh, Sarbari Ghosh, Madhurima Sarkar, Anamika Bose, Rathindranath Baral
Recent advances in tumor biology demand detailed analysis of the complex interaction of tumor cells with their adjacent microenvironment (tumor stroma) to understand the various mechanisms involved in tumor growth and metastasis. Mononuclear phagocytes or macrophages, a type of innate immune cells, defend the organism against infection and injury. On the otherhand, tumor associated macrophages (TAMs) constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype...
April 13, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28430642/immunocompetent-mouse-allograft-models-for-development-of-therapies-to-target-breast-cancer-metastasis
#12
Yuan Yang, Howard H Yang, Ying Hu, Peter H Watson, Huaitian Liu, Thomas R Geiger, Miriam R Anver, Diana C Haines, Philip Martin, Jeffrey E Green, Maxwell P Lee, Kent W Hunter, Lalage M Wakefield
Effective drug development to combat metastatic disease in breast cancer would be aided by the availability of well-characterized preclinical animal models that (a) metastasize with high efficiency, (b) metastasize in a reasonable time-frame, (c) have an intact immune system, and (d) capture some of the heterogeneity of the human disease. To address these issues, we have assembled a panel of twelve mouse mammary cancer cell lines that can metastasize efficiently on implantation into syngeneic immunocompetent hosts...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429359/the-role-of-angiogenesis-inhibitors-re-challenge-in-colorectal-cancer-previously-treated-with-bevacizumab-a-meta-analysis-of-randomized-controlled-trials
#13
Y-X Xiong, L Ren, Z-Q Wang, X-W Huang, Y-J Zhou
OBJECTIVE: The potential usefulness of angiogenesis inhibitors (AIs) re-challenge in the treatment of metastatic colorectal cancer (CRC) who previously treated with bevacizumab has not been established yet. MATERIALS AND METHODS: We identified relevant clinical studies through searching databases up to October 2016. Prospective clinical trials investigating AIs re-challenge in metastatic CRC were included for analysis. The primary endpoint was overall survival with secondary endpoint progression-free survival...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28428688/modulation-of-angiogenesis-proliferative-response-and-apoptosis-by-%C3%AE-sitosterol-in-rat-model-of-renal-carcinogenesis
#14
Ramalingam Sharmila, Ganapathy Sindhu
As expanded understanding of molecular tumor characteristics, which drive renal cancer growth and progression gives a promising future for renal carcinoma therapy. The objective of the present study was designed to examine the effect of β-sitosterol on a rat model of experimental renal carcinogenesis. Renal carcinogenesis was induced in rats treated with N-diethylnitrosamine (DEN; 200 mg/kg bw single i.p., injection) and ferric nitrilotriacetate (Fe-NTA; 9 mg Fe/kg bw i.p., twice a week for 16 weeks). β-sitosterol pretreatment (20 mg/kg bw in 0...
June 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28428054/modified-nanoparticle-mediated-il-12-immunogene-therapy-for-colon-cancer
#15
Xiaoxiao Liu, Xiang Gao, Songping Zheng, Bilan Wang, Yanyan Li, Chanjuan Zhao, Yagmur Muftuoglu, Song Chen, Ying Li, Haiyan Yao, Hui Sun, Qing Mao, Chao You, Gang Guo, Yuquan Wei
For the past few years, immunotherapy has recently shown considerable clinical benefit in CRC therapy, and the application of immunologic therapies in cancer treatments continues to increase perennially. Interleukin-12, an ideal candidate for tumor immunotherapy, could activate both innate and adaptive immunities. In this study, we developed a novel gene delivery system with a self-assembly method by MPEG-PLA and DOTAP(DMP) with zeta-potential value of 38.5mV and size of 37.5nm. The supernatant of lymphocytes treated with supernatant from Ct26 transfected pIL12 with DMP could inhibit Ct26 cells growth ex vivo...
April 17, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28425588/drug-resistance-reversal-by-combretastatin-a4-phosphate-loaded-with-doxorubicin-in-polymersomes-independent-of-angiogenesis-effect
#16
Jinfang Zhu, Mengying Hu, Liyan Qiu
OBJECTIVES: This study aimed to evaluate that the polymersomes (Ps-DOX-CA4P) dual-loaded with combretastatin-A4 phosphate (CA4P) and doxorubicin (DOX) overcame drug resistance and sensitized tumour cells to chemotherapeutic drugs. METHODS: Ps-DOX-CA4P were prepared by solvent evaporation method using mPEG-b-PLA as carriers. The potential capability of CA4P to reverse DOX resistance was verified by cytotoxicity test, apoptosis assay and cellular uptake of DOX. The comparison between free drugs and drug-loaded polymersomes was also made on a single-layer cell model and multicellular tumour spheroids to display the superiority of the drug vehicles...
April 20, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28424759/antiangiogenesis-for-advanced-non-small-cell-lung-cancer-in-the-era-of-immunotherapy-and-personalized-medicine
#17
REVIEW
Samer Tabchi, Normand Blais
Over the past decade, patients with advanced non-small-cell lung cancer (NSCLC) have witnessed substantial advances in regards to therapeutic alternatives. Among newly developed agents, angiogenesis inhibitors were extensively tested in different settings and have produced some favorable outcomes despite several shortcomings. Bevacizumab is the most examined agent in this context and has demonstrated significant survival benefits when combined with standard chemotherapy in eligible patients. Preliminary results on the addition of bevacizumab to erlotinib in patients with EGFR-mutated NSCLC seem promising...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28423648/polyisoprenylated-cysteinyl-amide-inhibitors-disrupt-actin-cytoskeleton-organization-induce-cell-rounding-and-block-migration-of-non-small-cell-lung-cancer
#18
Elizabeth Ntantie, Jerrine Fletcher, Felix Amissah, Olufisayo O Salako, Augustine T Nkembo, Rosemary A Poku, Francis O Ikpatt, Nazarius S Lamango
The malignant potential of Non-Small Cell Lung Cancer (NSCLC) is dependent on cellular processes that promote metastasis. F-actin organization is central to cell migration, invasion, adhesion and angiogenesis, processes involved in metastasis. F-actin remodeling is enhanced by the overexpression and/or hyper-activation of some members of the Rho family of small GTPases. Therefore, agents that mitigate hyperactive Rho proteins may be relevant for controlling metastasis. We previously reported the role of polyisoprenylated cysteinyl amide inhibitors (PCAIs) as potential inhibitors of cancers with hyperactive small GTPases...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423625/inhibition-activity-of-a-disulfide-stabilized-diabody-against-basic-fibroblast-growth-factor-in-lung-cancer
#19
Yaxiong Cai, Shuange Yao, Jiangchuan Zhong, Jinxia Zhang, Haowu Jiang, Yanrui Deng, Ning Deng
The over-expression of basic fibroblast growth factor (bFGF) plays a crucial role in the development, invasion and metastasis of lung cancer. Therefore, neutralizing antibodies against bFGF may inhibit the growth of lung cancer. In this study, a Disulfide-stabilized diabody (ds-Diabody) against bFGF was constructed by site-directed mutation and overlap extension PCR (SOE-PCR) at the position of VH44 and VL100 in the scFv. The ds-Diabody was constructed and expressed in Pichia pastoris. We found that the ds-Diabody against bFGF could efficiently suppress the proliferation, migration and invasion of human lung cancer A549 cells in vitro...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422724/utilizing-combinatorial-engineering-to-develop-tie2-targeting-antagonistic-angiopoetin-2-ligands-as-candidates-for-anti-angiogenesis-therapy
#20
Tomer Shlamkovich, Lidan Aharon, William A Barton, Niv Papo
In many human cancers, the receptor tyrosine kinase (RTK) Tie2 plays important roles in mediating proliferation, survival, migration and angiogenesis. Thus, molecules that could potently inhibit activation of the Tie2 receptor would have a significant impact on cancer therapy. Nevertheless, attempts to develop Tie2-targeted inhibitors have met with little success, and there is currently no FDA-approved therapeutic selectively targeting Tie2. We used a combinatorial protein engineering approach to develop a new generation of angiopoietin (Ang) 2-derived Tie2 antagonists as potential cancer therapeutics and as tools to study angiogenesis...
April 4, 2017: Oncotarget
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