Lynch syndrome is caused by germline mutations in DNA mismatch repair (MMR) genes. Both microsatellite instability (MSI) testing and immunohistochemical analyses (IHC) of colon cancers are valuable diagnostic strategies for Lynch syndrome. We sought to determine whether these markers of MMR deficiency were also detectable in pre-cancerous colorectal adenomas. Fifteen subjects with a germline MMR gene mutation who had 44 adenomas removed during surveillance colonoscopy were identified. MSI testing and IHC for MLH1 , MSH2 , and MSH6 were performed. MSI was detected in 23 adenomas. There was a significant association between MSI and high-grade dysplasia (P ‫؍‬ 0.006) and distal location (P ‫؍‬ 0.0008). Loss of MMR protein by IHC was detected in 31 adenomas. A significant association was observed between loss of staining by IHC and high-grade dysplasia (P ‫؍‬ 0.04). Among the 40 adenomas in which both MSI tests and IHC were performed , the presence of a germline mutation correlated with an abnormal MSI result in 58% of cases , an abnormal IHC result in 70% of cases , and either an abnormal MSI or IHC result in 73% of cases. The combination of MSI and IHC testing in colorectal adenomas is a sensitive screen for the detection of Lynch syndrome and may be particularly useful when Lynch syndrome is suspected and adenomatous polyps are the only tissues available for

MITOSTATIN, a novel putative tumor suppressor gene induced by decorin overexpression, is expressed in most normal human tissues but is markedly down-regulated in advanced stages of mammary and bladder carcinomas. Mitostatin negatively affects cell growth, induces cell death and regulates the expression and activation levels of Hsp27. In this study, we demonstrated that ectopic expression of Mitostatin in PC3, DU145, and LNCaP prostate cancer cells not only induced a significant reduction in cell growth, but also inhibited migration and invasion. Moreover, Mitostatin inhibited colony formation in soft-agar of PC3 and LNCaP cells as well as tumorigenicity of LNCaP cells in nude mice. Conversely, targeting endogenous Mitostatin by siRNA and anti-sense strategies in PC3 and DU145 prostate cancer cells enhanced the malignant phenotype in both cell lines. In agreement of these anti-oncogenic roles, we discovered that Mitostatin was absent in ∼35% (n = 124) of prostate tumor samples and its overall reduction was associated with advanced cancer stages. Collectively, our findings indicate that MITOSTATIN may acts as a tumor suppressor gene in prostate cancer and provide a novel cellular and molecular mechanism to be further exploited and deciphered in our understanding of prostate cancer progression.

Nitrofurantoin is an antimicrobial agent that is commonly used for the treatment of recurrent urinary tract infection. Nitrofurantoin pulmonary toxicity can present as acute, subacute, or chronic respiratory disease. Common manifestations are dry cough, chest pain, dyspnea, and hypoxemia. Skin rash, arthralgia, and abnormal transaminases are occasionally present. Chest imaging shows patchy infiltrates and fibrosis. Treatment includes discontinuing the medication. Although the role of corticosteroids has not been well described, patients with respiratory symptoms or hypoxemia may benefit from a trial of corticosteroid therapy.

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