H-REV107-1 Stimulates Growth in Non-Small Cell Lung Carcinomas via the Activation of Mitogenic Signaling

H-REV107-1, a known member of the class II tumor suppressor gene family, is involved in the regulation of differentiation and survival. We analyzed H-REV107-1 in non-small cell lung carcinomas, in normal lung, and in immortalized and tumor-derived cell lines. Sixty-eight percent of lung tumors revealed positive H-REV107-1-specific staining. Furthermore, survival analysis demonstrated a significant association of cytoplasmic H-REV107-1 with decreased patient survival. This suggested that H-REV107-1, known as a tumor suppressor, plays a different role in non-small cell lung carcinomas. Knock-down of H-REV107-1 expression in lung carcinoma cells inhibited anchorage-dependent and anchorage-independent growth whereas overexpression of H-REV107-1 induced tumor cell proliferation. Consistent with results of the survival analysis, cytoplasmic localization of the protein was essential for this growth-inducing function. Analysis of signaling pathways potentially involved in this process demonstrated that overexpression of H-REV107-1 stimulated RAS-GTPase activity, ERK1,2 phosphorylation, and caveolin-1 expression in the cell lines analyzed. These results indicate that H-REV107-1 is deficient in its function as a tumor suppressor in non-small cell lung carcinomas and is required for proliferation and anchorage-independent growth in cells expressing high levels of the protein, thus contributing to tumor progression in a subset of non-small cell lung carcinomas

Incidence of infections in patients with giant cell arteritis: a cohort study.

OBJECTIVE: Giant cell arteritis (GCA) is the most frequent form of vasculitis in adults. We sought to estimate the infectious risk associated with GCA and its treatment. METHODS: We conducted a matched historical cohort study using data from The Health Improvement Research Network. Patients with newly diagnosed GCA were matched with up to 6 non-GCA patients by age, sex, general practice, and date of entry into the cohort. Random-effects Poisson regression models were used to obtain incidence rates and rate ratios for lower respiratory tract infections (LRTI), urinary tract infections (UTI), and sepsis, as well as for the subset of these that comprised serious infections (pneumonias, upper UTI, and sepsis). Effect modification by age, sex, and time since diagnosis of GCA was assessed. RESULTS: A total of 1,664 patients with GCA were matched to 8,078 patients without GCA. Overall, 805 (48%) of the GCA patients and 3,007 (37%) of the non-GCA patients experienced ≥1 episode of systemic infection during followup, with adjusted rate ratios for LRTI, UTI, and serious infections of 1.48 (95% confidence interval [95% CI] 1.34-1.65), 1.27 (95% CI 1.10-1.46), and 1.55 (95% CI 1.22-1.96), respectively (P < 0.001 for all). The rate ratio for sepsis was 1.63 (95% CI 0.78-3.40, P = 0.20). Rate ratios for infection were highest in the first 6 months following diagnosis of GCA and in patients age <75 years, but did not vary by sex. CONCLUSION: This is the first study to show that patients with GCA are at increased risk of systemic infections, particularly in the first few months following diagnosis. New GCA medications that allow steroid sparing are needed to treat this condition