Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives

E Clair McClung, Robert M WenhamDepartment of Gynecologic Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USAAbstract: Patients with platinum-resistant ovarian cancer have progression of disease within 6 months of completing platinum-based chemotherapy. While several chemotherapeutic options exist for the treatment of platinum-resistant ovarian cancer, the overall response to any of these therapies is ~10%, with a median progression-free survival of 3–4 months and a median overall survival of 9–12 months. Bevacizumab (Avastin), a humanized, monoclonal antivascular endothelial growth factor antibody, has demonstrated antitumor activity in the platinum-resistant setting and was recently approved by US Food and Drug Administration for combination therapy with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan. This review summarizes key clinical trials investigating bevacizumab for recurrent, platinum-resistant ovarian cancer and provides an overview of efficacy, safety, and quality of life data relevant in this setting. While bevacizumab is currently the most studied and clinically available antiangiogenic therapy, we summarize recent studies highlighting novel alternatives, including vascular endothelial growth factor-trap, tyrosine kinase inhibitors, and angiopoietin inhibitor trebananib, and discuss their application for the treatment of platinum-resistant ovarian cancer.Keywords: bevacizumab, angiogenesis, ovarian cancer, platinum-resistant ovarian cancer, recurrent ovarian cance

STATE AND SOCIETY AT TEOTIHUACAN, MEXICO

Between 100 BCE and 200 CE, the city of Teotihuacan grew rapidly, most of the Basin of Mexico population was relocated in the city, immense civic-religious structures were built, and symbolic and material evidence shows the early importance of war. Rulers were probably able and powerful. Subsequently the city did not grow, and government may have become more collective, with significant constraints on rulers\u27 powers. A state religion centered on war and fertility deities presumably served elite interests, but civic consciousness may also have been encouraged. A female goddess was important but probably not as pervasive as has been suggested. Political control probably did not extend beyond central Mexico, except perhaps for some outposts, and the scale and significance of commerce are unclear. Teotihuacan\u27s prestige, however, spread widely in Mesoamerica, manifested especially in symbols of sacred war, used for their own ends by local elites

DddY, a periplasmic dimethylsulfoniopropionate lyase found in taxonomically diverse species of Proteobacteria

The abundant compatible solute dimethylsulfoniopropionate (DMSP) is made by many marine algae. Different marine bacteria catabolise DMSP by various mechanisms, some of which liberate the environmentally important gas dimethyl sulfide (DMS). We describe an enzyme, DddY, which cleaves DMSP into DMS plus acrylate and is located in the bacterial periplasm, unlike other DMSP lyases that catalyse this reaction. There are dddY-like genes in strains of Alcaligenes, Arcobacter and Shewanella, in the β-, ɛ- and γ-proteobacteria, respectively. In Alcaligenes, dddY is in a cluster of ddd and acu genes that resemble, but also have significant differences to, those in other bacteria that catabolise both DMSP and acrylate. Although production of DMS and transcription of Alcaligenes dddY are both apparently inducible by pre-growth of cells with DMSP, this substrate must be catabolised to form acrylate, the bona fide coinducer