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Angiogenesis and cancer therapy

Junyi Che, Anqi Tao, Shun Chen, Xiaoming Li, Yi Zhao, Weien Yuan
Small interfering RNA (siRNA) has increased the hope for highly-efficient treatment of gene-related diseases. However, the stable and efficient delivery of therapeutic nucleic acids is a prerequisite for the successful clinical translation of RNA interfering therapy. To achieve this, we condensed the low molecular weight polyethyleneimine (PEI, Mw < 2000) with 2,6-pyridinedicarboxaldehyde (PDA) to synthesize a biologically responsive and degradable cationic polymer (abbreviated to PDAPEI) which was utilized as a gene vector for the delivery of a VEGF-A shRNA expression plasmid DNA (pDNA)...
October 19, 2016: Scientific Reports
Ralph D Sanderson, Michael Elkin, Alan C Rapraeger, Neta Ilan, Israel Vlodavsky
Because of its impact on multiple biological pathways, heparanase has emerged as a major regulator of cancer, inflammation and other disease processes. Heparanase accomplishes this by degrading heparan sulfate which regulates the abundance and location of heparin-binding growth factors thereby influencing multiple signaling pathways that control gene expression, syndecan shedding and cell behavior. In addition, heparanase can act via non-enzymatic mechanisms that directly activate signaling at the cell surface...
October 18, 2016: FEBS Journal
Zhen Wang, Jun-Qiang Chen, Jin-Lu Liu, Lei Tian
Tumor microenvironment (TME) plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Exosome is an important part of TME. Exosomes are small vesicles formed in vesicular bodies with a diameter of 30-100 nm and a classic "cup" or "dish" morphology. They can contain microRNAs, mRNAs, DNA fragments and proteins, which are shuttled from a donor cell to recipient cells. Exosomes secreted from tumor cells are called tumor-derived (TD) exosomes. There is emerging evidence that TD exosomes can construct a fertile environment to support tumor proliferation, angiogenesis, invasion and premetastatic niche preparation...
October 19, 2016: Journal of Translational Medicine
Nicola Maurea, Paolo Spallarossa, Christian Cadeddu, Rosalinda Madonna, Donato Mele, Ines Monte, Giuseppina Novo, Pasquale Pagliaro, Alessia Pepe, Carlo G Tocchetti, Concetta Zito, Giuseppe Mercuro
The US National Cancer Institute estimates that cardiotoxicity (CTX) from target therapy refers mostly to four groups of drugs: epidermal growth factor receptor 2 inhibitors, angiogenic inhibitors, directed Abelson murine leukemia viral oncogene homolog inhibitors, and proteasome inhibitors. The main cardiotoxic side-effects related to antiepidermal growth factor receptor 2 therapy are left ventricular systolic dysfunction and heart failure. Angiogenesis inhibitors are associated with hypertension, left ventricular dysfunction/heart failure, myocardial ischemia, QT prolongation, and thrombosis...
May 2016: Journal of Cardiovascular Medicine
Nicola Maurea, Carmela Coppola, Giovanna Piscopo, Francesca Galletta, Gennaro Riccio, Emanuela Esposito, Claudia De Lorenzo, Michelino De Laurentiis, Paolo Spallarossa, Giuseppe Mercuro
The progress in cancer therapy and the increase in number of long-term survivors reveal the issue of cardiovascular side-effects of anticancer drugs. Cardiotoxicity has become a significant problem, and the risks of adverse cardiac events induced by systemic drugs need to be seriously considered. Potential cardiovascular toxicities linked to anticancer agents include arrhythmias, myocardial ischemia and infarction, hypertension, thromboembolism, left ventricular dysfunction, and heart failure. It has been shown that several anticancer drugs seriously affect the cardiovascular system, such as ErbB2 inhibitors, vascular endothelial growth factor (VEGF) inhibitors, multitargeted kinase inhibitors, Abelson murine leukemia viral oncogene homolog inhibitors, and others...
May 2016: Journal of Cardiovascular Medicine
Alexander Reinthaller
Angiogenesis plays a pivotal role in normal ovarian physiology as well as in the formation and progression of ovarian cancer. Several well-designed phase II and III trials studied the efficacy of antiangiogenic agents in advanced ovarian cancer. The results of these trials demonstrated significantly prolonged progression-free survival when antiangiogenic agents were used as a maintenance therapy. To date, no effect on overall survival could be ascertained. The most widely studied antiangiogenic agent, bevacizumab - a monoclonal humanized antibody against vascular endothelial growth factor - was effective in all phases of the disease (first-line therapy, platinum-sensitive and platinum-resistant recurrence)...
2016: Memo
Domenico Ribatti, Beatrice Nico, Simona Ruggieri, Roberto Tamma, Giovanni Simone, Anita Mangia
Several data support a central role for angiogenesis in breast cancer growth and metastasis. Observational studies have demonstrated that microvascular density (MVD) is a prognostic factor in invasive breast cancer, whereas others reached the opposite conclusion. Vascular endothelial growth factor is the most important angiogenic factor with proven significance in breast cancer, as it has been assessed in both experimental and clinical studies. Triple-negative breast cancer (TNBC) is a type of breast cancer which lacks estrogen, progesterone, and HER-2/neu receptors...
October 2016: Translational Oncology
Sophia Frentzas, Eve Simoneau, Victoria L Bridgeman, Peter B Vermeulen, Shane Foo, Eleftherios Kostaras, Mark R Nathan, Andrew Wotherspoon, Zu-Hua Gao, Yu Shi, Gert Van den Eynden, Frances Daley, Clare Peckitt, Xianming Tan, Ayat Salman, Anthoula Lazaris, Patrycja Gazinska, Tracy J Berg, Zak Eltahir, Laila Ritsma, Jacco van Rheenen, Alla Khashper, Gina Brown, Hanna Nyström, Malin Sund, Steven Van Laere, Evelyne Loyer, Luc Dirix, David Cunningham, Peter Metrakos, Andrew R Reynolds
The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing...
October 17, 2016: Nature Medicine
Lindsey E Minion, Krishnansu S Tewari
Introduction Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF) (Avastin; Genetech, Inc, San Francisco, CA). Angiogenesis is blocked by the binding of bevacizumab to VEGF, inhibiting the binding of this ligand to the VEGF receptor. On August 14, 2014 the Food and Drug Administration (FDA) approved use of bevacizumab in persistent, recurrent, or metastatic cervical cancer. Areas Covered Herein we review pharmacodynamics and kinetics, clinical data and treatment-related toxicities of bevacizumab in the treatment of metastatic, recurrent or persistent cervical cancer...
October 17, 2016: Expert Review of Anticancer Therapy
Elham Ajorlou, Ahmad Yari Khosroushahi
PURPOSE: The dawn of the state-of-the-art methods of cancer treatments, nano-based delivery systems, has dispensed with the mainstream chemotherapy for being inadequate in yielding productive results and the numerous reported side effects. The popularity of this complementary approach in the course of the last two decades has been primarily attributed to its capacity to elevate the therapeutic index of anticancer drugs as well as removing the impassable delivery barriers in solid tumors with the minimal damage to the normal tissues...
October 15, 2016: Cancer Chemotherapy and Pharmacology
A Caporali, A Martello, V Miscianinov, D Maselli, R Vono, G Spinetti
During physiological development and after a stressor event, vascular cells communicate with each other to evoke new vessel formation - a process known as angiogenesis. This communication occurs via direct contact and via paracrine release of proteins and nucleic acids, both in a free form or encapsulated into micro-vesicles. In diseases with an altered angiogenic response, such as cancer and diabetic vascular complications, it becomes of paramount importance to tune the cell communication process. Endothelial cell growth and migration are essential processes for new vessel formation, and pericytes, together with some classes of circulating monocytes, are important endothelial regulators...
October 11, 2016: Pharmacology & Therapeutics
Nikolas M Eleftheriou, Jonas Sjölund, Matteo Bocci, Eliane Cortez, Se-Jin Lee, Sara I Cunha, Kristian Pietras
Angiogenesis occurs early in tumor development, sustains primary tumor growth and provides a route for metastatic escape. The TGF-β family receptors modulate angiogenesis via endothelial-cell specific pathways. Here we investigate the interaction of two such receptors, ALK1 and endoglin, in pancreatic neuroendocrine tumors (PanNET). Independently, ALK1 and endoglin deficiencies exhibited genetically divergent phenotypes, while both highly correlate to an endothelial metagene in human and mouse PanNETs. A concurrent deficiency of both receptors synergistically decreased tumor burden to a greater extent than either individual knockdown...
October 12, 2016: Oncotarget
Dimitrios Zardavas, Konstantinos Tryfonidis, Theodora Goulioti, Martine Piccart
INTRODUCTION: The potential of molecular targeted therapy to improve the clinical outcomes of patients with early-stage breast cancer (BC) as adjuvant therapy has been first demonstrated through endocrine treatment. The introduction of HER2 blockade, through the successful clinical development of trastuzumab, changed the natural history of HER2-positive BC subtype. AREAS COVERED: There are ongoing efforts to augment further the use of targeted agents as adjuvant treatment in BC, hoping that early introduction of targeted therapy blocking key oncogenic drivers of micro-residual disease, will significantly improve clinical outcomes...
October 14, 2016: Expert Review of Anticancer Therapy
Georgios Lolas, Lasse Jensen, George C Bourantas, Vasiliki Tsikourkitoudi, Konstantinos Syrigos
With the exception of a limited number of sites in the body, primary tumors infrequently lead to the demise of cancer patients. Instead, mortality and a significant degree of morbidity result from the growth of secondary tumors in distant organs. Tumor survival, growth and dissemination are associated with the formation of both new blood vessels (angiogenesis) and new lymph vessels (lymphagenesis or lymphangiogenesis). Although intensive research in tumor angiogenesis has been going on for the past four decades, experimental results in tumor lymphangiogenesis began to appear only in the last 10 years...
2016: Advances in Experimental Medicine and Biology
E Benedetti, M d'Angelo, A Ammazzalorso, G Gravina, C Laezza, A Antonosante, G Panella, B Cinque, L Cristiano, A C Dhez, C Astarita, R Galzio, M G Cifone, R Ippoliti, R Amoroso, E Di Cesare, A Giordano, A Cimini
Glioblastoma is the most-common cancer in the brain and with an increasing incidence. Despite major advances in the field, there is no curative therapy for GB to date. Many solid tumors, including GB, experienced metabolic reprogramming in order to sustain uncontrolled proliferation, hypoxic conditions and angiogenesis. PPARs, member of the steroid hormone receptor superfamily, are particularly involved in the control of energetic metabolism, particularly lipid metabolism, which has been reported deregulated in gliomas...
October 13, 2016: Journal of Cellular Physiology
Fatemeh Mahmoodi, Hassan Akrami
Placental growth factor (PlGF) a member of the vascular endothelial growth factor family regulates some cell processes such as survival, growth of vascular endothelial cells, invasiveness and also involves in pathological angiogenesis and metastasis in most cancers. Cancer stem cells are believed to be the main reason for the tumor relapse and resistance to therapy. These cells have various characteristics as same as normal tissue-specific adult stem cells, including self-renewability and potent to differentiate into various cell types...
October 13, 2016: Journal of Cellular Biochemistry
Qingxin Zhou, Yuekun Zhu, Xiaoli Wei, Jianhua Zhou, Liang Chang, Hong Sui, Yu Han, Daxun Piao, Ruihua Sha, Yuxian Bai
Altered expression of microRNA-590-5p (miR-590-5p) is involved in tumorigenesis, however, its role in colorectal cancer (CRC) remains to be determined. In this study, we focused on examining the effects of different expression levels of miR-590-5p in cancer cells and normal cells. Results showed that there are lower expression levels of miR-590-5p in human CRC cells and tissues than in normal control cells and tissues. Similarly, in our xenograft mouse model, knockdown of miR-590-5p promoted the progression of CRC...
October 13, 2016: Cell Death & Disease
Lai Yue Chan, David J Craik, Norelle L Daly
Peptide analogues derived from bioactive hormones such as somatostatin or certain growth factors have great potential as angiogenesis inhibitors for cancer applications. In an attempt to combat emerging drug resistance many FDA-approved anti-angiogenesis therapies are co-administered with cytotoxic drugs as a combination therapy to target multiple signaling pathways of cancers. However, cancer therapies often encounter limiting factors such as high toxicities and side effects. Here, we combined two anti-angiogenic epitopes that act on different pathways of angiogenesis into a single non-toxic cyclic peptide framework, namely MCoTI-II (Momordica cochinchinensis trypsin inhibitor-II), and subsequently assessed the anti-angiogenic activity of the novel compound...
October 13, 2016: Scientific Reports
Steven A Lacy, Dale R Miles, Linh T Nguyen
Cabozantinib inhibits receptor tyrosine kinases involved in tumor angiogenesis and metastasis. The capsule formulation (Cometriq(®)) is approved for the treatment of progressive metastatic medullary thyroid cancer at a 140-mg free base equivalent dose. The tablet formulation (Cabometyx™, 60-mg free base equivalent dose) is approved for the treatment of renal cell carcinoma following anti-angiogenic therapy. Cabozantinib displays a long terminal plasma half-life (~120 h) and accumulates ~fivefold by day 15 following daily dosing based on area under the plasma concentration-time curve (AUC)...
October 12, 2016: Clinical Pharmacokinetics
Carmine D'Aniello, Maria G Vitale, Azzurra Farnesi, Lorenzo Calvetti, Maria M Laterza, Carla Cavaliere, Chiara Della Pepa, Vincenza Conteduca, Anna Crispo, Ferdinando De Vita, Francesco Grillone, Enrico Ricevuto, Michele De Tursi, Rocco De Vivo, Marilena Di Napoli, Sabrina C Cecere, Gelsomina Iovane, Alfonso Amore, Raffaele Piscitelli, Giuseppe Quarto, Salvatore Pisconti, Gennaro Ciliberto, Piera Maiolino, Paolo Muto, Sisto Perdonà, Massimiliano Berretta, Emanuele Naglieri, Luca Galli, Giacomo Cartenì, Ugo De Giorgi, Sandro Pignata, Gaetano Facchini, Sabrina Rossetti
Axitinib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) after failure of prior treatment with Sunitinib or cytokine. The present study is an Italian Multi-Institutional Retrospective Analysis that evaluated the outcomes of Axitinib, in second-line treatment of mRCC. The medical records of 62 patients treated with Axitinib, were retrospectively reviewed. The Progression Free Survival (PFS), the Overall Survival (OS), the Objective Response Rate (ORR), the Disease Control Rate (DCR), and the safety profile of axitinib and sunitinib-axitinib sequence, were the primary endpoint...
2016: Frontiers in Pharmacology
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