Tuberculosis (TB) has scourged humankind for millennia, and latent infection affects nearly one-third of today's world population. The emergence of multidrug-resistant (MDR)-TB is a major global threat and reflects treatment failure of drug-sensitive disease. MDR-TB management is a burden for patients and society; success rates are unacceptably low with prolonged treatment duration. Mycobacterium tuberculosis (Mtb) possesses the ability to transform into a dormant state in which it can persist in the face of antimicrobial treatment and host defense. This sub-population of persisters is largely responsible for lengthy and difficult treatment. Targeting persistent bacilli could eventually improve the treatment success rate (currently 50-65 %) and shorten duration of treatment. A subset of therapies in the pipeline, termed therapeutic vaccines, use the host immune response to attack Mtb. The historical occurrence of an exacerbated host response has resulted in a negative perception of therapeutic vaccines. Thus, a renewed concept of immunotherapy is needed. We review current perspectives of immunotherapy in MDR-TB based on the knowledge of TB immunology and briefly discuss the profiles of several therapeutic vaccine products.

BACKGROUNDCyclooxygenase (Cox) is the main target enzyme for the nonsteroidal antiinflammatory drugs that have been shown to suppress carcinogenesis in both experimental models and epidemiologic studies.METHODSTo evaluate its utility as an intermediate biomarker in bronchial chemoprevention trials, the authors examined Cox 1 and Cox 2 expression in normal and premalignant bronchial epithelial cells and nonsmall cell lung carcinoma (NSCLC) samples using an immunohistochemical staining technique. Included in the current study were 101 NSCLC samples and 77 bronchial biopsy samples obtained from 15 healthy smokers.RESULTSIn the normal bronchial epithelium, Cox 2 expression was found to be completely negative whereas Cox 1 expression was noted in a few scattered cells. The areas of basal cell hyperplasia and squamous metaplasia demonstrated the same pattern. There were relatively more Cox 2‐positive tumors, as defined by positive staining in > 10% of tumor cells, than Cox 1‐positive tumors (30 of 101 tumors [30%] vs. 14 of 101 tumors [14%]; P = 0.01). When tumor types were considered, there were more Cox 2‐positive adenocarcinomas compared with squamous cell carcinomas (21 of 51 adenocarcinomas [41%] vs. 9 of 46 squamous cell carcinomas [20%]; P = 0.03). In contrast, fewer adenocarcinomas tended to show Cox 1 expression compared with squamous cell carcinomas (4 of 51 adenocarcinomas [8%] vs. 9 of 46 squamous cell carcinomas [20%]; P = 0.14). Although smokers tended to have more Cox 2‐positive tumors than nonsmokers (29 of 91 tumors in the smokers [32%] vs. 1 of 10 tumors in the nonsmokers [10%]; P = 0.15), there was no statistically significant relation found between Cox 1 or Cox 2 expression and smoking status or prognostically significant clinicopathologic features.CONCLUSIONSThe results of the current study suggest that Cox 1 and Cox 2 expression may not be a useful intermediate biomarker in bronchial chemoprevention trials. Nevertheless, considering the patterns of Cox 1 and Cox 2 expression in tumor cells, Cox expression status may be a useful parameter when designing treatment strategies for a subset of NSCLC patients. Cancer 2002;94:1023–31. © 2002 American Cancer Society.DOI 10.1002/cncr.10262

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Death receptor 4 (DR4) gene is a candidate tumor suppressor gene that has a role in apoptotic pathway. It was reported in literature that polymorphisms in DR4 gene lead to susceptibility to many cancers. In accordance with this information, we aimed to investigate the association between G422A, C626G, A683C and A1322G polymorphisms in DR4 gene and lung cancer. We selected 60 patients with lung cancer (LC) and 30 healthy, sex and age matched volunteers randomly. Four polymorhisms, G422A, C626G, A683C and A1322G, in DR4 gene were analyzed with Polymerase Change Reaction (PCR)--Restriction Fragment Lenght Polymorphism (RFLP) and Amplification Refractory Mutation System (ARMS) techniques in both groups. Our results showed that there are no statistically significances between the patients and controls in terms of the G422A, C626G, A683C and A1322G polymorphisms in DR4 gene (p > 0,05). Our findings showed no role of DR4 gene polymorphisms in susceptibility to LC and provide a plausible explanation for DR4 genetic heterogeneity in LC susceptibility.

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