Multicenter Phase II Trial of Sunitinib in the Treatment of Nongastrointestinal Stromal Tumor Sarcomas

PURPOSE To evaluate the potential benefit of continuous daily dosing sunitinib in patients with advanced nongastrointestinal stromal tumor (GIST) sarcomas. PATIENTS AND METHODS A total of 53 patients with advanced non-GIST soft tissue sarcomas received sunitinib 37.5 mg daily. Primary end point was Response Evaluation Criteria in Solid Tumors defined response. Secondary end points were stable disease at 16 and 24 weeks. [(18)F]-fluorodeoxyglucose positron emission tomography was performed on a subset of 24 patients at baseline and after 10 to 14 days of therapy. Results Forty-eight patients were eligible for response. One patient (desmoplastic round cell tumor [DSRCT]) achieved a confirmed partial response (PR) and remained on study for 56 weeks. Ten patients (20%) achieved stable disease for at least 16 weeks. Metabolic PR was seen in 10 (47%) of 21 of patients. Metabolic stable disease was seen in 11 (52%) of 21. There were no unexpected toxicities observed. CONCLUSION Sunitinib demonstrated notable evidence of metabolic response in several patients with non-GIST sarcoma. The relevance of disease control observed in subtypes with an indolent natural history is unknown, however, the durable disease control observed in DSRCT, solitary fibrous tumor, and giant cell tumor of bone suggests that future evaluation of sunitinib in these subtypes may be warranted

Extensive genome analysis identifies novel plasmid families in Clostridium perfringens

Globally, the anaerobic bacterium Clostridium perfringens causes severe disease in a wide array of hosts; however, C. perfringens strains are also carried asymptomatically. Accessory genes are responsible for much of the observed phenotypic variation and virulence within this species, with toxins frequently encoded on conjugative plasmids and many isolates carrying up to 10 plasmids. Despite this unusual biology, current genomic analyses have largely excluded isolates from healthy hosts or environmental sources. Accessory genomes, including plasmids, also have often been excluded from broader scale phylogenetic investigations. Here we interrogate a comprehensive collection of 464 C. perfringens genomes and identify the first putative non-conjugative enterotoxin (CPE)-encoding plasmids and a putative novel conjugative locus (Bcp) with sequence similarity to a locus reported from Clostridium botulinum. We sequenced and archived 102 new C. perfringens genomes, including those from rarely sequenced toxinotype B, C, D and E isolates. Long-read sequencing of 11 C. perfringens strains representing all toxinotypes (A-G) identified 55 plasmids from nine distinct plasmid groups. Interrogation of the 464 genomes in this collection identified 1045 plasmid-like contigs from the nine plasmid families, with a wide distribution across the C. perfringens isolates. Plasmids and plasmid diversity play an essential role in C. perfringens pathogenicity and broader biology. We have expanded the C. perfringens genome collection to include temporal, spatial and phenotypically diverse isolates including those carried asymptomatically in the gastrointestinal microbiome. This analysis has resulted in the identification of novel C. perfringens plasmids whilst providing a comprehensive understanding of species diversity

Osteosarcomas of jaw: Experience of a single centre

WOS: 000347297600003PubMed ID: 24780088Although osteosarcoma is the most common primary malignant tumour of bone, osteosarcomas of jaw are rare. In osteosarcomas of jaw, evaluating the clinicopathological factors affecting the prognosis is not easy because of different approaches to diagnosis, treatment, and follow-up. This study reviewed 14 cases of JOS that were diagnosed between 1990-2010, in terms of age, gender, site, clinical history, histopathologic type and histopathologic grade, treatment, and prognosis. Median age was 35 years, while male: female ratio was 1.8:1. Eight tumours were located in the mandible. Osteoblastic differentiation was the predominant feature in seven cases followed by chondroid osteosarcoma (four cases), fibroblastic osteosarcoma, low-grade (parosteal) osteosarcoma associated with fibrous dysplasia, and postradiation osteosarcoma (one cases each). During follow-up, recurrence was seen in four patients at least once and they all died. In conclusion, early diagnosis and complete resection seems to be effective in prognosis. Therefore, clinicians and pathologists should be aware of its characteristics and main differential diagnosis to avoid late recognition