Evidence suggests that the histone deacetylase, SIRT1, is a mediator of life span extension by calorie restriction; however, SIRT1 may paradoxically increase the risk of cancer. To better understand the relationship among SIRT1, energy balance, and cancer, two experiments were done. First, a transgenic mouse model of prostate cancer (transgenic adenocarcinoma of mouse prostate; TRAMP) was used to determine the role of energy balance on SIRT1 expression and the effect of cancer stage on SIRT1 and hypermethylated in cancer-1 (HIC-1). Second, immunohistochemistry was done on human prostate tumors to determine if SIRT1 was differentially expressed in tumor cells versus uninvolved cells. Results show that SIRT1 is not increased in the dorsolateral prostate (DLP) of calorierestricted mice during carcinogenesis. In contrast, when examined in the DLP as a function of pathologic score, SIRT1 was significantly elevated in mice with poorly differentiated adenocarcinomas compared with those with less-advanced disease. HIC-1, which has been shown to regulate SIRT1 levels, was markedly reduced in the same tumors, suggesting that a reduction in HIC-1 may be in part responsible for the increased expression of SIRT1 in prostatic adenocarcinomas. Furthermore, immunostaining of human prostate tumors showed that cancer cells had greater SIRT1 expression than uninvolved cells. In conclusion, DLP SIRT1 expression from calorie-restricted mice was not altered during carcinogenesis. However, SIRT1 expression was increased in mice with poorly differentiated adenocarcinomas and in human prostate cancer cells. Because SIRT1 may function as a tumor promoter, these results suggest that SIRT1 should be considered as a potential therapeutic target for prostate cancer. [Cancer Res 2007;67(14):6612-8]

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Slllnlmal-yMorbidity in humans infected with Schistosoma mansoni results primarily from the deposition of parasite eggs in portal areas where they induce a granulomatous response. In mice infected with this helminth granuloma formation is a CD4 + T helper (Th) cell-dependent process that is associated with a strong Th2 cytokine response which appears to evolve through a Th0 phase. In this report, we asked whether endogenously synthesized or exogenously induced interferon (IFN)3' through its suppression of Th2 cell expansion exerts a regulatory role on egg pathology. Depletion of IFN-3, or natural killer cells resulted in a marked enhancement of granuloma formation around intravenously injected eggs and was associated with increased Th2 and decreased Thl and interleukin (IL)12 mRNA expression. Similar changes occurred when egg-injected mice were treated with neutralizing monoclonal antibodies specific for IL-12 indicating a role for this cytokine in the regulation of the granulomatous response. In contrast, treatment with exogenous rlL-12 profoundly inhibited primary granuloma formation while increasing IFN-% IL-2, IL-10, and IL-12 pulmonary mRNA levels and suppressing IL-4, IL-5, IL-6, and IL-13 mRNA expression. Cytokine depletion studies indicated that the effects of IL-12 could be attributed primarily to increased IFN-% Importantly, IL-12 also inhibited secondary granuloma formation in mice presensitized with eggs demonstrating a role for the cytokine in reversing established Th2-type responses. Moreover, mice sensitized with eggs in combination with IL-12 to precommit them toward a Thl response developed only minimal granulomas upon subsequent egg challenge. The latter findings suggest that simultaneous vaccination with antigen plus IL-12 may provide a strategy for the prevention of schistosome egg pathology as well as other diseases stemming from Th2 cytokine production.

EUS-FNA is highly accurate in identifying patients with suspected pancreatic cancer, especially when other modalities have failed. Major complications after EUS-FNA are rare, and minor complications are similar to those reported for upper endoscopy. It seems that follow-up at 1 wk might capture all of the adverse events related to EUS-FNA.

Endoscopic ultrasound (EUS) is used to detect and delineate the extent of lesions in the gastrointestinal tract, periluminal lymph nodes, pancreas and hepatobiliary tree, left kidney, spleen, and adrenal glands. EUS-guided fine-needle aspiration (FNA) has added a new dimension to the capabilities of EUS because it permits characterization of the lesion, thereby enabling triage of patients for more efficient and effective management. This review focuses on the advantages and limitations of EUS-FNA, including a discussion of potential pitfalls in the diagnosis of commonly aspirated deep-seated lesions, such as those of the pancreas and lymph nodes. It also addresses the practical considerations associated with establishing an effective service and the importance of an integrated approach in which the cytopathologist undertakes a key role, interacting extensively with the endoscopist and the patient management team. EUS-FNA is a sensitive modality that enables specific and accurate diagnosis of deep-seated lesions. Samples can be obtained effectively from small lesions (< 25 mm), irrespective of the organ site. On-site assessment permits a highly accurate preliminary diagnosis of malignancy for samples obtained by EUS-FNA and provides an opportunity to increase the diagnostic yield of samples.

In a comparative study 88 patients were diagnosed as suffering from kala-azar (visceral leishmaniasis) using 3 parasitological methods simultaneously. Splenomegaly was absent in 4 cases. In 84 patients with splenomegaly, splenic aspiration appeared to be the most sensitive method (96.4%), followed by bone marrow aspiration (70.2%) and lymph node aspiration (58.3%). There was no relation between titres in the direct agglutination test and parasite load as determined by the number of parasitological methods which were positive or parasite density in splenic aspirates. Splenic aspiration and bone marrow aspiration were compared as an assessment of cure in kala-azar. In 6 (13%) of 46 patients tested, parasites were found, all by splenic aspiration. Bone marrow showed parasites in one of these. The literature with regard to parasitological investigations before and after treatment is reviewed.

Resveratrol, a natural polyphenolic phytochemical, has been reported to act as an antioxidant and provide anticancer activities. We hypothesized that resveratrol would exert a chemopreventive effect against prostate cancer via regulation of sex steroid receptor and growth factor signaling pathways. In the current study, Transgenic Adenocarcinoma Mouse Prostate males were fed resveratrol (625 mg resveratrol per kg AIN-76A diet) or phytoestrogen-free, control diet (AIN-76A) starting at 5 weeks of age. Mechanisms of action and histopathology studies were conducted at 12 and 28 weeks of age, respectively. Resveratrol in the diet significantly reduced the incidence of poorly differentiated prostatic adenocarcinoma by 7.7-fold. In the dorsolateral prostate, resveratrol significantly inhibited cell proliferation, increased androgen receptor, estrogen receptor-beta, and insulin-like growth factor-1 receptor, and significantly decreased insulin-like growth factor (IGF)-1 and phospho-extracellular regulating kinase 1 (phospho-ERK 1). In the ventral prostate, resveratrol significantly reduced cell proliferation and phospho-ERKs 1 and 2, but did not significantly alter insulin-like growth factor-1 receptor and IGF-1. Serum total testosterone, free testosterone, estradiol, dihydrotestosterone and sex hormone-binding globulin (SHBG) concentrations and Simian Virus-40 large T antigen expression in the prostate were not altered in resveratrol-treated mice. Total resveratrol concentration in the blood serum of 12-week-old mice treated for 3 weeks with 625 mg resveratrol per kg diet was 52 +/- 18 nM. The decrease in cell proliferation and the potent growth factor, IGF-1, the down-regulation of downstream effectors, phospho-ERKs 1 and 2 and the increase in the putative tumor suppressor, estrogen receptor-beta, provide a biochemical basis for resveratrol suppressing prostate cancer development.

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