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Nobuaki Suzuki, Shoichi Hazama, Haruo Iguchi, Kazuhiro Uesugi, Hiroaki Tanaka, Kosei Hirakawa, Atsushi Aruga, Takashi Hatori, Hidenobu Ishizaki, Yuzo Umeda, Toshiyoshi Fujiwara, Tetsuya Ikemoto, Mitsuo Shimada, Kazuhiko Yoshimatsu, Ryoichi Shimizu, Hiroto Hayashi, Koichiro Sakata, Hiroko Takenouchi, Hiroto Matsui, Yoshitaro Shindo, Michihisa Iida, Yasunobu Koki, Hideki Arima, Hiroyuki Furukawa, Tomio Ueno, Shigefumi Yoshino, Yusuke Nakamura, Masaaki Oka, Hiroaki Nagano
We previously conducted a phase I clinical trial combining the HLA-A*2402-restricted KIF20A-derived peptide vaccine with gemcitabine for advanced pancreatic cancer (PC) and confirmed its safety and immunogenicity in cancer patients. In this study, we conducted a multicenter, single-armed, phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide. We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine...
October 26, 2016: Cancer Science
Dario L Longo, Rachele Stefania, Chiara Callari, Francesco De Rose, Riccardo Rolle, Laura Conti, Lorena Consolino, Francesca Arena, Silvio Aime
A dynamic contrast enhanced (DCE) approach for tumor photoacoustic (PA) imaging is described. Novel water soluble melanin-based derivatives are synthesized that exhibit good PA properties, stability, safety and accumulation in tumor bearing mice. This melanin derivative is capable to characterize tumor vasculature and to monitor vessel permeability changes upon antiangiogenic treatment. DCE-PA imaging can assess functional response to cancer treatments.
October 26, 2016: Advanced Healthcare Materials
Chong Chen, Kun Liu, Yupeng Xu, Pengwei Zhang, Yan Suo, Yi Lu, Wenyuan Zhang, Li Su, Qing Gu, Huamao Wang, Jianren Gu, Zonghai Li, Xun Xu
Anti-vascular endothelial growth factor (VEGF) therapies are widely used for the treatment of neovascular fundus diseases such as diabetic retinopathy. However, these agents need to be injected intravitreally, because their strong hydrophilicity and high molecular weight prevent them from penetrating cell membranes and complex tissue barriers. Moreover, the repeated injections that are required can cause infection and tissue injury. In this study, we used in vivo-directed evolution phage display technology to identify a novel dodecapeptide, named CC12, with the ability to penetrate the ocular barrier in a noninvasive (via conjunctival sac instillation) or minimally invasive (via retrobulbar injection) manner...
September 30, 2016: Biomaterials
Ettore D'Argento, Sabrina Rossi, Giovanni Schinzari, Antonia Strippoli, Michele Basso, Alessandra Cassano, Carlo Barone
New treatments-as immunotherapies and new antiangiogenic agents-are now available in second-line setting for patients affected by EGFR wild-type and ALK-negative non-small-cell lung cancer (NSCLC). Nintedanib, ramucirumab, nivolumab and pembrolizumab have to be included in the therapeutic sequences for patients affected by NSCLC, but no clear selection criteria are to date offered, except for patients with PD-L1 expression ≥50 %. Performance status, smoking habits and comorbidities should be considered as clinical criteria in order to select the appropriate treatment, but also tumour characteristics as histotype, platinum resistance and rapid progression after a first-line therapy should be taken into account...
December 2016: Current Treatment Options in Oncology
Julienne K Muenzner, Bernhard Biersack, Alexander Albrecht, Tobias Rehm, Ulrike Lacher, Wolfgang Milius, Angela Casini, Jing-Jing Zhang, Ingo Ott, Viktor Brabec, Olga Stuchlikova, Ion C Andronache, Detlef Schuppan, Leonard Kaps, Rainer Schobert
Four gold(I) carbene complexes featuring 4-ferrocenyl substituted imidazol-2-ylidene ligands were investigated for antiproliferative and antivascular properties. They were active against a panel of seven cancer cell lines, including multidrug-resistant ones, with low micromolar or nanomolar IC50 (72 h) values, according to their lipophilicity and cellular uptake. The delocalised lipophilic cationic complexes 8 and 10 acted by increasing the reactive oxygen species in two ways: via a genuine ferrocene effect and by inhibiting the thioredoxin reductase...
October 20, 2016: Chemistry: a European Journal
Loiy E Ahmed Hassan, Saad S Dahham, Sultan Ayesh Mohammed Saghir, Abdelhafeez M A Mohammed, Nagla M Eltayeb, Amin Malik Shah Abdul Majid, Aman Shah Abdul Majid
BACKGROUND: Balanite aegyptiaca (L.) Delile, is a plant with extensive medicinal properties. Its stem bark is traditionally known for its spasmolytic and antiepileptic properties and used to treat yellow fever, jaundice and syphilis. Angiogenesis (sprouting of new blood vessels) is crucial for tumor growth and metastasis. The goal of this study is investigate the antiangiogenic, cytotoxicity and antioxidant activity as well as antitumor in vivo properties of B. aegyptiaca stem bark extracts...
October 19, 2016: BMC Complementary and Alternative Medicine
Susan R Mallery, Daren Wang, Brian Santiago, Ping Pei, Steven Schwendeman, Kari Nieto, Richard Spinney, Meng Tong, George Koutras, Byungdo B Han, Andrew S Holpuch, James C Lang
Over 1/3 of patients who have undergone oral squamous cell carcinoma (OSCC) surgical resections develop life-threatening and often untreatable recurrences. A variety of drugs, intended for management of recurrent or disseminated cancers, were designed to exploit cancer cells' reliance upon overexpressed receptors and gratuitous signaling. Despite their conceptual promise, clinical trials showed these agents lacked efficacy and were often toxic. These findings are consistent with evasion of pathway-targeted treatments via extensive signaling redundancies and compensatory mechanisms common to cancers...
October 18, 2016: Cancer Prevention Research
Perparim Limani, Michael Linecker, Philipp Kron, Panagiotis Samaras, Bernhard Pestalozzi, Roger Stupp, Alexander Jetter, Philipp Dutkowski, Beat Müllhaupt, Andrea Schlegel, Claude Nicolau, Jean-Marie Lehn, Henrik Petrowsky, Bostjan Humar, Rolf Graf, Pierre-Alain Clavien
BACKGROUND: Solid tumors, such as hepato-pancreato-biliary cancer, develop tumor hypoxia with tumor growth. Despite advances in surgery, a majority of these patients are in an unresectable condition. At this stage standard cytotoxic chemotherapy regimens are applied with limited success. Novel biological treatment options based on an antiangiogenic mechanism of action neglect other hypoxia mediated mechanisms (e.g. epithelial-mesenchymal transition, Warburg effect, and immunological response) leading to an increased invasiveness with a poor outcome...
October 19, 2016: BMC Cancer
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
Esther A Guzmán, Dedra Harmody, Tara P Pitts, Brunilda Vera-Diaz, Priscilla L Winder, Yichao Yu, Amy E Wright
Pancreatic cancer presents one of the most negative prognosis of all cancers as it has usually metastasized by the time a patient is diagnosed. The American Cancer Society estimates that 93% of patients will die within 5 years of diagnosis, highlighting the need for new drugs to treat this disease. Interleukin 8 (IL-8) mediates the angiogenesis of tumors arising from Ras mutations, which are present in about 90% of pancreatic adenocarcinomas. Overexpression of IL-8 in pancreatic tumors is believed to promote tumor angiogenesis and to activate survival signaling pathways...
October 5, 2016: Anti-cancer Drugs
Michael S Lee, Bert H O'Neil
Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies, with differences in prognosis and effective therapies. Traditionally, NETs have been characterized by tumor grade, site of primary tumor, functional status, and presence of underlying familial syndrome. However, increased feasibility and utilization of next-generation sequencing and other methodologies have revealed new genomic and epigenetic aberrations. In the last decade, treatment options available for metastatic well-differentiated gastroenteropancreatic (GEP) NETs have expanded, with approval of antiangiogenic and mTOR-directed targeted therapies, and our armamentarium of active therapies is likely to further increase...
October 2016: Journal of Gastrointestinal Oncology
Ho Shin Kim, Mannkyu Hong, Jihyae Ann, Suyoung Yoon, Cong-Truong Nguyen, Su-Chan Lee, Ho-Young Lee, Young-Ger Suh, Ji Hae Seo, Hoon Choi, Jun Yong Kim, Kyu-Won Kim, Joohwan Kim, Young-Myeong Kim, So-Jung Park, Hyun-Ju Park, Jeewoo Lee
Based on the lead compound L-80 (compound 2), a potent heat shock protein 90 (HSP90) inhibitor, a series of C-ring truncated deguelin analogs were designed, synthesized and evaluated for Hypoxia Inducible Factor-1α (HIF-1α) inhibition as a primary screening method. Their structure-activity relationship was investigated in a systematic manner by varying the A/B ring, linker and D/E ring, respectively. Among the synthesized inhibitors, compound 5 exhibited potent HIF-1α inhibition in a dose-dependent manner and significant antitumor activity in human non-small cell lung carcinoma (H1299), with better activities than L-80...
September 30, 2016: Bioorganic & Medicinal Chemistry
Prabhu Thirusangu, V Vigneshwaran, T Prashanth, B R Vijay Avin, Vikas H Malojirao, H Rakesh, Shaukath Ara Khanum, Riaz Mahmood, B T Prabhakar
Hypoxia is a feature of all solid tumours, contributing to tumour progression. Activation of HIF-1α plays a critical role in promoting tumour angiogenesis and metastasis. Since its expression is positively correlated with poor prognosis for cancer patients, HIF-1α is one of the most convincing anticancer targets. BP-1T is a novel antiproliferative agent with promising antiangiogenic effects. In the present study, the molecular mechanism underlying cytotoxic/antiangiogenic effects of BP-1T on tumour/non-tumour angiogenesis was evaluated...
October 14, 2016: Angiogenesis
M Alsina, C Hierro, J Tabernero
No abstract text is available yet for this article.
October 13, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Jacob A Miller, Elizabeth E Bennett, Roy Xiao, Rupesh Kotecha, Samuel T Chao, Michael A Vogelbaum, Gene H Barnett, Lilyana Angelov, Erin S Murphy, Jennifer S Yu, Manmeet S Ahluwalia, John H Suh, Alireza M Mohammadi
BACKGROUND: The primary dose-limiting toxicity of stereotactic radiosurgery (SRS) is radiation necrosis (RN), which occurs after approximately 5% to 10% of treatments. This adverse event may worsen neurologic deficits, increase the frequency and cost of imaging, and necessitate prolonged treatment with steroids or antiangiogenic agents. Previous investigations have primarily identified lesion size and dosimetric constraints as risk factors for RN in small populations. We hypothesized that disease histology, receptor status, and mutational status are associated with RN...
September 1, 2016: International Journal of Radiation Oncology, Biology, Physics
O Rapalino, E M Ratai
Magnetic resonance spectroscopy (MRS) is a magnetic resonance-based imaging modality that allows noninvasive sampling of metabolic changes in normal and abnormal brain parenchyma. MRS is particularly useful in the differentiation of developmental or non-neoplastic disorders from neoplastic processes. MRS is also useful during routine imaging follow-up after radiation treatment or during antiangiogenic treatment and for predicting outcomes and treatment response. The objective of this article is to provide a concise but thorough review of the basic physical principles, important applications of MRS in brain tumor imaging, and future directions...
November 2016: Magnetic Resonance Imaging Clinics of North America
Melania Olivieri, Emanuele Amata, Shila Vinciguerra, Jole Fiorito, Giovanni Giurdanella, Filippo Drago, Nunzia Caporarello, Orazio Prezzavento, Emanuela Arena, Loredana Salerno, Antonio Rescifina, Gabriella Lupo, Carmelina Daniela Anfuso, Agostino Marrazzo
(±)-MRJF22 [(±)-2], a novel prodrug of haloperidol metabolite II obtained by conjugation to valproic acid via an ester bond, exhibits antiangiogenic activity being able to reduce Human Retinal Endothelial Cells (HREC) viability in a comparable manner to Bevacizumab. Moreover, (±)-2 was able to significantly reduce viable cells count, endothelial cell migration and tube formation in Vascular endothelial growth factor A (VEGF-A) stimulated HREC cultures.
October 14, 2016: Journal of Medicinal Chemistry
Magdalena Lukamowicz-Rajska, Christiane Mittmann, Michael Prummer, Qing Zhong, Jens Bedke, Jörg Hennenlotter, Arnulf Stenzl, Axel Mischo, Svenja Bihr, Manuela Schmidinger, Ursula Vogl, Iris Blume, Christoph Karlo, Peter Schraml, Holger Moch
A number of treatments targeting VEGF or mTOR pathways have been approved for metastatic clear cell Renal Cell Carcinoma (ccRCC), but the majority of patients show disease progression after first line therapy with a very low rate of complete or long-term responders. It has been shown that miRs may play a role in prediction of treatment response in various cancer types. The aim of our study was to identify a miR signature predictive for RCC patients' response to antiangiogenic tyrosine kinase inhibitor (TKI) treatment in the first line therapy...
October 12, 2016: Oncotarget
Letizia Canu, Silvia Pradella, Elena Rapizzi, Rossella Fucci, Andrea Valeri, Vittorio Briganti, Valentino Giachè, Gabriele Parenti, Tonino Ercolino, Massimo Mannelli
Metastatic pheochromocytomas (PHEOs) and paragangliomas (sPGLs) are rare neural crest-derived tumors with a poor prognosis. About 50% of them are due to germ-line mutations of the SDHB gene. At present, there is no cure for these tumors. Their therapy is palliative and represented by different options among which antiangiogenic drugs, like sunitinib, have been hypothesized to be effective especially in malignant SDHB mutated tumors. We report the effects of sunitinib therapy in a SDHB mutation carrier affected by a malignant sPGL...
October 10, 2016: Archives of Endocrinology and Metabolism
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