Combining Vaccines with Conventional Therapies for Cancer

Preclinical and clinical investigations currently underway are employing novel strategies for combining vaccines with conventional and experimental anticancer therapies. To date, the FDA has not approved a therapeutic cancer vaccine. However, the results of recent investigations suggest an increasing role for vaccines in new models of combination therapy for many types of cancer. This article reviews and discusses therapeutic cancer strategies that employ vaccines in combination with local radiation, chemotherapy, hormone therapy, and anti-CTLA-4 mAb. Preclinical studies have shown that certain anticancer agents have immune modulatory effects that result in up-regulation of surface expression of MHC molecules, tumor-associated antigens, or Fas on malignant cells, rendering them more susceptible to immune destruction. Preliminary results of clinical studies using combination strategies have demonstrated a postvaccination antigen cascade, prolonged time to disease progression, and improved overall survival. Several larger randomized trials are ongoing, and more are required to support these findings.     

Synthesis and anti-tuberculous activity of diesters based on isosteviol and dicarboxylic acids

Diesters based on isosteviol and dicarboxylic acids were synthesized and tested for antituberculous activity. Isosteviol and some of its derivatives exhibit appreciable tuberculostatic properties in vitro, the activity being dependent on the length of the polymethylene spacer connecting two ent-beyeran fragments. The mechanism of the antituberculous action of isosteviol derivatives are discussed. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 9, pp. 12–13, September, 2006.     

18F-FDG PET/CT for detecting nodal metastases in patients with oral cancer staged N0 by clinical examination and CT/MRI.

(18)F-FDG PET has a high accuracy in staging head and neck cancer, but its role in patients with clinically and radiographically negative necks (N0) is less clear. In particular, the value of combined PET/CT has not been determined in this group of patients. METHODS: In a prospective study, 31 patients with oral cancer and no evidence of lymph node metastases by clinical examination or CT/MRI underwent (18)F-FDG PET/CT before elective neck dissection. PET/CT findings were recorded by neck side (left or right) and lymph node level. PET/CT findings were compared with histopathology of dissected nodes, which was the standard of reference. RESULTS: Elective neck dissections (26 unilateral, 5 bilateral; a total of 36 neck sides), involving 142 nodal levels, were performed. Only 13 of 765 dissected lymph nodes harbored metastases. Histopathology revealed nodal metastases in 9 of 36 neck sides and 9 of 142 nodal levels. PET was TP in 6 nodal levels (6 neck sides), false-negative in 3 levels (3 neck sides), true-negative in 127 levels (23 neck sides), and false-positive in 6 levels (4 neck sides). The 3 false-negative findings occurred in metastases smaller than 3 mm or because of inability to distinguish between primary tumor and adjacent metastasis. TP and false-positive nodes exhibited similar standardized uptakes (4.8 +/- 1.1 vs. 4.2 +/- 1.0; P = not significant). Sensitivity and specificity were 67% and 85% on the basis of neck sides and 67% and 95% on the basis of number of nodal levels, respectively. If a decision regarding the need for neck dissection had been based solely on PET/CT, 3 false-negative necks would have been undertreated, and 4 false-positive necks would have been overtreated. CONCLUSION: (18)F-FDG PET/CT can identify lymph node metastases in a segment of patients with oral cancer and N0 neck. A negative test can exclude metastatic deposits with high specificity. Despite reasonably high overall accuracy, however, the clinical application of PET/CT in the N0 neck may be limited by the combination of limited sensitivity for small metastatic deposits and a relatively high number of false-positive findings. The surgical management of the N0 neck should therefore not be based on PET/CT findings alone.     

Highlights in asthma 2005.

It is usual at the end of a year for top tens to feature large in our collective consciousness. These inevitably include the occasional controversial selection and without fail will overlook a number of gems, whether in the field of literature, art, or science. The approaches to such compilations include personal selections, convening expert committees through to letting the market decide. However, it is well recognised that experts can be wrong and markets distorted. A novel approach to identifying the key publications in the field of medicine, Faculty of 1000 Medicine (http://www.f1000medicine.com), uses faculty evaluations to assign ratings to published papers within topics and categories, bringing a flavour of the dynamism of post hoc peer review to biological sciences that exists in other fields of scholarship. Archives of Disease in Childhood has also developed a market led system of peer evaluation through its web based top ten most read articles feature.     

The criminal purchase of firearm ammunition.

OBJECTIVE: Laws that prohibit certain individuals from owning firearms also pertain to ammunition. Whereas retail sales of firearms to criminals are regularly disrupted by instant background checks, sales of ammunition are essentially unchecked and the rate at which criminals acquire ammunition is unknown. This research describes the ammunition market and estimates the rate at which criminals are acquiring ammunition. DESIGN: Criminal background checks conducted on individuals purchasing ammunition in the City of Los Angeles in April and May 2004. SETTING: Los Angeles, CA, USA. SUBJECTS: Ammunition purchasers. MAIN OUTCOME MEASURES: Criminal activity that prohibits one from owning, purchasing, or possessing ammunition. RESULTS: 2.6% (95% CI 1.9% to 3.2%) of ammunition purchasers had a prior felony conviction or another condition that prohibited them from possessing ammunition. During the study period prohibited possessors purchased 10,050 rounds of ammunition in Los Angeles. CONCLUSIONS: These estimates suggest that monitoring ammunition transactions may help reduce the supply of ammunition to criminals and the frequency of injuries from felonious gun assaults. Such a record can also provide information for generating leads on illegal firearm possession.     

Healthcare worker competencies for disaster training

Background  

Although training and education have long been accepted as integral to disaster preparedness, many currently taught practices are neither evidence-based nor standardized. The need for effective evidence-based disaster training of healthcare staff at all levels, including the development of standards and guidelines for training in the multi-disciplinary health response to major events, has been designated by the disaster response community as a high priority. We describe the application of systematic evidence-based consensus building methods to derive educational competencies and objectives in criteria-based preparedness and response relevant to all hospital healthcare workers.     

MRI evaluation of bulky tumor masses in the mesentery and bladder involvement in peritoneal carcinomatosis

AIM: Peritonectomy procedures with intraperitoneal chemohyperthermia are an effective but costly treatment for peritoneal carcinomatosis (PC). Consequently a proper selection of patients is necessary. We evaluated the benefit of MRI prior to surgery, in the detection of two of the main surgery contraindications: bulky mesenteric tumors and bladder implants. METHODS: Three experts retrospectively reviewed abdominal and pelvic MRI from 19 cases of surgically proved PC (ovary: 7; colorectal: 7; gastric: 2; pseudomyxoma peritonei: 2; appendix: 1). RESULTS: Mesenteric tumors were always identified as hypersignal masses on axial and coronal fat suppression gadolinium-enhanced T1 images (n=3). Three out of five bladder implants were detected. The two cases of bladder implants that were not detected on MRI were missed because the bladder was not filled. The best sequence for the detection of bladder involvement was axial T2-weighted images with bladder filling. CONCLUSIONS: Evaluating the preoperative resectability of PC is crucial for patient management. MRI seems to reliably detect bulky mesenteric tumors and bladder implants on condition the bladder is filled and appropriate sequences are used.