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https://www.readbyqxmd.com/read/28443762/prediction-of-therapy-response-in-ovarian-cancer-where-are-we-now
#1
Khalid El Bairi, Mariam Amrani, Abdul Hafeez Kandhro, Said Afqir
Therapy resistance is a major challenge in the management of ovarian cancer (OC). Advances in detection and new technology validation have led to the emergence of biomarkers that can predict responses to available therapies. It is important to identify predictive biomarkers to select resistant and sensitive patients in order to reduce important toxicities, to reduce costs and to increase survival. The discovery of predictive and prognostic biomarkers for monitoring therapy is a developing field and provides promising perspectives in the era of personalized medicine...
April 26, 2017: Critical Reviews in Clinical Laboratory Sciences
https://www.readbyqxmd.com/read/28441383/the-oral-vegf-receptor-tyrosine-kinase-inhibitor-pazopanib-in-combination-with-the-mek-inhibitor-trametinib-in-advanced-cholangiocarcinoma
#2
Rachna T Shroff, Mark Yarchoan, Ashley O'Connor, Denise Gallagher, Marianna L Zahurak, Gary Rosner, Chimela Ohaji, Susan Sartorius-Mergenthaler, Vivek Subbiah, Ralph Zinner, Nilofer S Azad
BACKGROUND: Cholangiocarcinoma is an aggressive malignancy with limited therapeutic options. MEK inhibition and antiangiogenic therapies have individually shown modest activity in advanced cholangiocarcinoma, whereas dual inhibition of these pathways has not been previously evaluated. We evaluated the safety and efficacy of combination therapy with the oral VEGF receptor tyrosine kinase inhibitor pazopanib plus the MEK inhibitor trametinib in patients with advanced cholangiocarcinoma...
April 25, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28438067/gene-therapy-for-patients-with-advanced-solid-tumors-a-phase-i-study-using-gene-electrotransfer-to-muscle-with-the-integrin-inhibitor-plasmid-amep
#3
Iben Spanggaard, Karin Dahlstroem, Line Laessoee, Rasmus Hvass Hansen, Helle Hjorth Johannesen, Helle Westergren Hendel, Céline Bouquet, Pierre Attali, Julie Gehl
BACKGROUND: Gene electrotrotransfer describes the use of electric pulses to transfer DNA to cells. Particularly skeletal muscle has potential for systemic secretion of therapeutic proteins. Gene electrotransfer to muscle using the integrin inhibitor plasmid AMEP (Antiangiogenic MEtargidin Peptide) was investigated in a phase I dose escalation study. Primary objective was safety. MATERIAL AND METHODS: Patients with metastatic or locally advanced solid tumors, without further standard treatments available, were treated with once-only gene electrotransfer of plasmid AMEP to the femoral muscle...
April 25, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28438066/angiogenesis-inhibitors-in-tackling-recurrent-glioblastoma
#4
Thomas Hundsberger, David A Reardon, Patrick Y Wen
Despite aggressive multimodality treatment of glioblastoma, outcome remains poor and patients mostly die of local recurrences. Besides reoperation and occasionally reirradiation, systemic treatment of recurrent glioblastoma consists of alkylating chemotherapy (lomustine, temozolomide), bevacizumab and combinations thereof. Unfortunately, antiangiogenic agents failed to improve survival either as a monotherapy or in combination treatments. This review provides current insights into tumor-derived escape mechanisms and other areas of treatment failure of antiangiogenic agents in glioblastoma...
April 24, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28434806/fibronectin-adherent-peripheral-blood-derived-mononuclear-cells-as-paclitaxel-carriers-for-glioblastoma-treatment-an-in-vitro-study
#5
Marco Paolo Schiariti, Francesco Restelli, Paolo Ferroli, Anna Benetti, Angiola Berenzi, Anna Ferri, Valentina Ceserani, Emilio Ciusani, Moris Cadei, Gaetano Finocchiaro, Augusto Pessina, Eugenio Parati, Roberto Pallini, Giulio Alessandri
BACKGROUND: Glioblastoma (GBM) represents the most aggressive malignant brain tumor in adults, with a risible median life expectancy despite gold standard treatment. Novel drug-delivery methods have been explored. Here we evaluated the possibility to use mononuclear cells (MCs) belonging to the monocytic-dendritic lineage as drug-carrier. METHODS: MCs were obtained from 10 patients harboring a GBM, and from healthy volunteers, considered as controls. GBM tissue was also obtained from patients...
April 20, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28428895/suppression-of-retinal-neovascularization-by-inhibition-of-galectin-1-in-a-murine-model-of-oxygen-induced-retinopathy
#6
Ning Yang, Wenxi Zhang, Tao He, Yiqiao Xing
Galectin-1 (Gal-1) has been proved to be an important factor in the process of tumor angiogenesis recently. As a small molecule, OTX008 serves as a selective inhibitor of Gal-1. In this study, the role of Gal-1 and the antiangiogenic effect of OTX008 on retinal neovascularization (RNV) were investigated using a mouse model of oxygen-induced retinopathy. The outcome indicated that Gal-1 was overexpressed and closely related to retinal neovessels in OIR. After intravitreal injection of OTX008 at P12, the RNV was significantly reduced at P17, measuring by cross-sectional H&E staining and whole-mount fluorescence...
2017: Journal of Ophthalmology
https://www.readbyqxmd.com/read/28427164/early-tumour-shrinkage-as-a-survival-predictor-in-patients-with-recurrent-glioblastoma-treated-with-bevacizumab-in-the-avareg-randomized-phase-ii-study
#7
Alba A Brandes, Gaetano Finocchiaro, Vittorina Zagonel, Michele Reni, Alessandra Fabi, Claudia Caserta, Alicia Tosoni, Marica Eoli, Giuseppe Lombardi, Matteo Clavarezza, Alexandro Paccapelo, Stefania Bartolini, Luigi Cirillo, Raffaele Agati, Enrico Franceschi
BACKGROUND: Disease assessment for recurrent glioblastoma (GBM) represents a challenge, especially with the use of antiangiogenic agents. Moreover, validated neuroradiological predictors of outcome are lacking. Recently, the concept of early tumor shrinkage (ETS) has been developed to better assess the ability of treatments in determining a rapid and remarkable tumor response.The aim of the study was to evaluate the role of ETS in predicting survival of GBM patients treated with BEVMETHODS: We examined the radiological data of patients with recurrent GBM treated with bevacizumab (BEV) or fotemustine (FTM) in the randomized phase II AVAREG trial (EudraCT: 2011-001363-46)...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424759/antiangiogenesis-for-advanced-non-small-cell-lung-cancer-in-the-era-of-immunotherapy-and-personalized-medicine
#8
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/28424351/mir-191-suppresses-angiogenesis-by-activation-of-nf-%C3%AE%C2%BAb-signaling
#9
Yuan Gu, Emmanuel Ampofo, Michael D Menger, Matthias W Laschke
MicroRNAs (miRNAs) are powerful regulators of diverse biologic processes. However, the function of most miRNAs in angiogenesis remains elusive. In this study, we identified miR-191-5p (miR-191) as a potent inhibitor of blood vessel development. Transfection of human dermal microvascular endothelial cells with miR-191 mimic (miR-191m) inhibited their proliferation, migration, and tube formation. Moreover, vascular sprouting of miR-191m-transfected mouse aortic rings was significantly reduced when compared with controls...
April 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28422745/targeting-of-the-breast-cancer-microenvironment-with-a-potent-and-linkable-oxindole-based-antiangiogenic-small-molecule
#10
Orestis Argyros, Theodoros Karampelas, Aimilia Varela, Xenophon Asvos, Athanasios Papakyriakou, Adamantia Agalou, Dimitris Beis, Constantinos H Davos, Demosthenes Fokas, Constantin Tamvakopoulos
The clinical efficacy of antiangiogenic small molecules (e.g., sunitinib) in breast carcinoma has largely failed with substantial off-target toxicity. We rationally designed and evaluated preclinically a novel sunitinib analogue, SAP, with favourable pharmacological properties and the ability to be readily conjugated to a targeting peptide or antibody for active tumour targeting.SAP was evaluated in silico and in vitro in order to verify target engagement (e.g., VEGFR2). Pharmacokinetic and biodistribution parameters were determined in mice using LC-MS/MS...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420755/papers-of-note-in-science-translational-medicine9-385
#11
Leslie K Ferrarelli
This week's articles show that combining antiangiogenic therapy and immune checkpoint inhibition improves antitumor immunity.
April 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28419195/plasma-ctdna-ras-mutation-analysis-for-the-diagnosis-and-treatment-monitoring-of-metastatic-colorectal-cancer-patients
#12
J Vidal, L Muinelo, A Dalmases, F Jones, D Edelstein, M Iglesias, M Orrillo, A Abalo, C Rodríguez, E Brozos, Y Vidal, S Candamio, F Vázquez, J Ruiz, M Guix, L Visa, V Sikri, J Albanell, B Bellosillo, R López, C Montagut
Background: RAS assessement is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however genotyping of circulating tumor (ct)DNA offers clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice...
April 13, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28416742/model-driven-optimization-of-antiangiogenics-cytotoxics-combination-application-to-breast-cancer-mice-treated-with-bevacizumab-paclitaxel-doublet-leads-to-reduced-tumor-growth-and-fewer-metastasis
#13
Severine Mollard, Joseph Ciccolini, Diane-Charlotte Imbs, Raouf El Cheikh, Dominique Barbolosi, Sebastien Benzekry
Bevacizumab is the first-in-class antiangiogenic drug and is almost always administrated in combination with cytotoxics. Reports have shown that bevacizumab could induce a transient phase of vascular normalization, thus ensuring a better drug delivery when cytotoxics administration is adjuvant. However, determining the best sequence remains challenging. We have developed a mathematical model describing the impact of antiangiogenics on tumor vasculature. A 3.4 days gap between bevacizumab and paclitaxel was first proposed by our model...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409322/tyrosine-kinase-inhibitors-reprogramming-immunity-in-renal-cell-carcinoma-rethinking-cancer-immunotherapy
#14
REVIEW
L M A Aparicio, I P Fernandez, J Cassinello
The immune system regulates angiogenesis in cancer by way of both pro- and antiangiogenic activities. A bidirectional link between angiogenesis and the immune system has been clearly demonstrated. Most antiangiogenic molecules do not inhibit only VEGF signaling pathways but also other pathways which may affect immune system. Understanding of the role of these pathways in the regulation of immunosuppressive mechanisms by way of specific inhibitors is growing. Renal cell carcinoma (RCC) is an immunogenic tumor in which angiogenesis and immunosuppression work hand in hand, and its growth is associated with impaired antitumor immunity...
April 13, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28405545/maslinic-acid-inhibits-proliferation-of-renal-cell-carcinoma-cell-lines-and-suppresses-angiogenesis-of-endothelial-cells
#15
Parth Thakor, Wenzhe Song, Ramalingam B Subramanian, Vasudev R Thakkar, David A Vesey, Glenda C Gobe
Despite the introduction of many novel therapeutics in clinical practice, metastatic renal cell carcinoma (RCC) remains a treatment-resistant cancer. As red and processed meat are considered risk factors for RCC, and a vegetable-rich diet is thought to reduce this risk, research into plant-based therapeutics may provide valuable complementary or alternative therapeutics for the management of RCC. Herein, we present the antiproliferative and antiangiogenic effects of maslinic acid, which occurs naturally in edible plants, particularly in olive fruits, and also in a variety of medicinal plants...
2017: Journal of Kidney Cancer and VHL
https://www.readbyqxmd.com/read/28404866/combined-antiangiogenic-and-anti-pd-l1-therapy-stimulates-tumor-immunity-through-hev-formation
#16
Elizabeth Allen, Arnaud Jabouille, Lee B Rivera, Inge Lodewijckx, Rindert Missiaen, Veronica Steri, Kevin Feyen, Jaime Tawney, Douglas Hanahan, Iacovos P Michael, Gabriele Bergers
Inhibitors of VEGF (vascular endothelial growth factor)/VEGFR2 (vascular endothelial growth factor receptor 2) are commonly used in the clinic, but their beneficial effects are only observed in a subset of patients and limited by induction of diverse relapse mechanisms. We describe the up-regulation of an adaptive immunosuppressive pathway during antiangiogenic therapy, by which PD-L1 (programmed cell death ligand 1), the ligand of the negative immune checkpoint regulator PD-1 (programmed cell death protein 1), is enhanced by interferon-γ-expressing T cells in distinct intratumoral cell types in refractory pancreatic, breast, and brain tumor mouse models...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28404865/dual-angiopoietin-2-and-vegfa-inhibition-elicits-antitumor-immunity-that-is-enhanced-by-pd-1-checkpoint-blockade
#17
Martina Schmittnaegel, Nicolò Rigamonti, Ece Kadioglu, Antonino Cassará, Céline Wyser Rmili, Anna Kiialainen, Yvonne Kienast, Hans-Joachim Mueller, Chia-Huey Ooi, Damya Laoui, Michele De Palma
Pathological angiogenesis is a hallmark of cancer and a therapeutic target. Vascular endothelial growth factor A (VEGFA) and angiopoietin-2 (ANGPT2; also known as ANG2) are proangiogenic cytokines that sustain tumor angiogenesis and limit antitumor immunity. We show that combined ANGPT2 and VEGFA blockade by a bispecific antibody (A2V) provided superior therapeutic benefits, as compared to the single agents, in both genetically engineered and transplant tumor models, including metastatic breast cancer (MMTV-PyMT), pancreatic neuroendocrine tumor (RIP1-Tag2), and melanoma...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28401381/antiangiogenic-therapy-combined-with-immune-checkpoint-blockade-in-renal-cancer
#18
REVIEW
Teele Kuusk, Laurence Albiges, Bernard Escudier, Nikolaos Grivas, John Haanen, Thomas Powles, Axel Bex
Antiangiogenic therapy with vascular endothelial growth factor (VEGF) inhibitors is the current first-line treatment in metastatic renal cell carcinoma (mRCC). Immunotherapy with checkpoint inhibitor has been recently added to the armamentarium of mRCC treatment. These therapies are based on treatment with antibodies that block programmed cell death-1 (PD-1), programmed cell death ligand 1 (PD-L1) pathways, demonstrating impressive response rates and improved survival in several tumour types. So far, nivolumab is the only approved anti-PD-1 monoclonal antibody after VEGF therapy in mRCC...
April 11, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28397506/-coffee-in-cancer-chemoprevention
#19
J Neuwirthová, B Gál, P Smilek, P Urbánková
Coffee consumption is associated with a reduced risk of several diseases including cancer. Its chemopreventive effect has been studied in vitro, in animal models, and more recently in humans. Several modes of action have been proposed, namely, inhibition of oxidative stress and damage, activation of metabolizing liver enzymes involved in carcinogen detoxification processes, and anti-inflammatory effects. The antioxidant activity of coffee relies partly on its chlorogenic acid content and is increased during the roasting process...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28392885/the-transcription-factor-bach1-suppresses-the-developmental-angiogenesis-of-zebrafish
#20
Li Jiang, Meng Yin, Jie Xu, Mengping Jia, Shaoyang Sun, Xu Wang, Jianyi Zhang, Dan Meng
Bach1 disrupts Wnt/β-catenin signaling, reduces the proliferation, migration, and tube formation activity of endothelial cells (ECs), and suppresses angiogenesis in mice with surgically induced hind-limb ischemia (HLI). However, the function of Bach1 during developmental angiogenesis in zebrafish remains unclear. Here, we found that zebrafish Bach1 was expressed ubiquitously during early embryonic development in zebrafish. Bach1b mRNA injection of Tg(fli1:gfp) fish disrupted intersegmental vessels (ISV) and dorsal longitudinal anastomotic vessels (DLAV) and suppressed endogenous Wnt/β-catenin signaling and Wnt8a stimulated vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) gene expression at early embryonic stages of zebrafish...
2017: Oxidative Medicine and Cellular Longevity
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