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Purpose: To establish the clinical significance of calcium binding proteins S100A2 and S100A4 during progression of human prostate adenocarcinoma. Patients and Methods: Expression pattern of S100A2 and S100A4 was determined in normal human prostate epithelial cells (NHPE); virally transformed prostate epithelial cells (PZ-HPV-7); several human prostate carcinoma cells (22Rv1, DU145, LNCaP, and PC3); tissue samples obtained during transuretheral prostatic resection from patients with benign prostate hyperplasia (BPH), prostatitis, and adenocarcinoma; and paraffin-embedded sections from pair-matched benign and cancer specimens of different tumor grade. Results: High constitutive protein expression of S100A2 was observed in NHPE and PZ-HPV-7 cells, whereas its complete absence was observed in 22Rv1, DU145, LNCaP, and PC3 cells. Tissue samples of BPH and prostatitis exhibited higher mRNA and protein levels of S100A2 than low-grade cancer (Gleason score ≤ 6), whereas a complete loss was observed in high-grade cancer specimens (Gleason score > 6). Immunohistochemical analysis further confirmed high levels of S100A2 in benign tissues and a progressive loss with increasing tumor grade. The protein level of S100A4 was significantly higher in all carcinoma cells compared with NHPE and PZ-HPV-7 cells. The mRNA and protein level of S100A4 was significantly higher in high-grade cancer specimens compared with BPH, prostatitis, and low-grade cancer. The high levels of S100A4 observed in cancer tissue correlated with increasing tumor grade. Conclusion: Loss of S100A2 and increased expression of S100A4 may be an important event during progression of prostate cancer in humans.

Overexpression of cyclooxygenase (COX)-2 has been implicated in many pathologic conditions, including cancer. One practical inference of this finding is that sustained inhibition of COX-2 could serve as a promising target for prevention or therapy of cancer. Conventional nonsteroidal antiinflammatory drugs (NSAIDs) and recently developed COX-2-specific inhibitors have shown considerable promise in prevention of some forms of human cancer; however, its application is limited due to severe toxic side effects on normal cells. Therefore, there is a need to define novel, nontoxic dietary constituents with proven chemopreventive effects through other pathways that also possess COX-2 but not COX-1 inhibitory activity. Recent studies on green tea and its major polyphenolic constituent (-)epigallocatechin-3-gallate (EGCG) have established its remarkable cancer preventive and some cancer therapeutic effects. Here, we show that EGCG inhibits COX-2 without affecting COX-1 expression at both the mRNA and protein levels, in androgen-sensitive LNCaP and androgen-insensitive PC-3 human prostate carcinoma cells. Based on our study, it is tempting to suggest that a combination of EGCG with chemotherapeutic drugs could be an improved strategy for prevention and treatment of prostate cancer.

Incense smoke is increasingly being recognized as a potential environmental contaminant and is linked to malignant and non-malignant respiratory diseases. The detoxification of environmental contaminants including polycyclic aromatic hydrocarbons (PAHs) involves the induction of cytochrome P-450 family enzymes (CYPs) by PAHs. However, the detoxification of PAHs also results in the generation of reactive and unstable intermediary metabolites which are implicated in the oxidative stress, DNA damage, and inflammation. It is unclear whether CYPs are similarly induced by incense smoke, which incidentally contains substantial amounts of PAHs. Here, we examined the impact of long-term incense smoke exposure on the induction of CYPs in male Wister Albino rats. Incense smoke exposure significantly induced the expression of CYP1A1, CYP1A2, and CYP1B1 mRNAs in both lung and liver tissues. The extent of CYP1A1 and CYP1B1 induction was significantly higher in the liver compared to that in the lung, while that of CYP1A2 was greater in the lung than in liver. Incense smoke exposure also increased malondialdehyde and reduced glutathione levels in lung and liver tissues, and the catalase activity in the liver tissues to significant levels. Furthermore incense smoke exposure led to a marked increase in TNF-α and IL-4 levels. The data demonstrate for the first time the capacity of incense smoke to induce CYP1 family enzymes in the target and non-target tissues. Induction of CYPs increased oxidative stress and inflammation appear to be intimately linked to promote the carcinogenesis and health complications in people chronically exposed to incense smoke.

Flexible bronchoscopy (FB) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. However, bronchoscopy practices vary widely across India and worldwide. The three major respiratory organizations of the country supported a national-level expert group that formulated a comprehensive guideline document for FB based on a detailed appraisal of available evidence. These guidelines are an attempt to provide the bronchoscopist with the most scientifically sound as well as practical approach of bronchoscopy. It involved framing appropriate questions, review and critical appraisal of the relevant literature and reaching a recommendation by the expert groups. The guidelines cover major areas in basic bronchoscopy including (but not limited to), indications for procedure, patient preparation, various sampling procedures, bronchoscopy in the ICU setting, equipment care, and training issues. The target audience is respiratory physicians working in India and well as other parts of the world. It is hoped that this document would serve as a complete reference guide for all pulmonary physicians performing or desiring to learn the technique of flexible bronchoscopy.

Genetic polymorphisms of the folate pathway were moderate predictors of autism risk. MTHFR C677T and hyperhomocysteinemia have been identified as risk factors for autism worldwide. Synergistic interactions between MTHFR C677T and MTRR A66G increase homocysteine.