Monthly injection of 500 mg TU provides safe, effective, reversible, and reliable contraception in a high proportion of healthy fertile Chinese men.

No abstract

PTEN 4 (phosphatase and tensin homologue deleted on chromosome ten) is the first phosphatase identified as a tumor suppressor (1-3). Loss of function mutations or reduced expression of the PTEN gene are found at high frequencies in a wide variety of human tumors, including glioblastoma, as well as endometrial, prostate, colorectal, lung, and breast cancers. Experimental and clinical evidence demonstrate that PTEN is a critical tumor suppressor (4).PTEN acts primarily as a negative regulator of the phosphoinositide 3-kinase (PI3K) pathway by virtue of its lipid phosphatase activity (5-7). Loss of PTEN leads to an increase in the phosphatidylinositol 3-phosphate level, mimicking the effect of constitutive PI3K activation. Phosphatidylinositol 3-phosphate accumulation results in the activation of various protein kinases, including the PDK1 and PKB/AKT serine/threonine kinases. AKT is the central node in the PTEN-regulated pathway and activated AKT has been shown to promote cell cycle progression, cell growth, cell survival, cell migration, angiogenesis, protein synthesis, and glucose metabolism through phosphorylation of its substrates (8, 9).Aside from acting as a negative regulator of the PI3K pathway, which depends on its lipid phosphatase activity, PTEN also functions independently of its lipid phosphatase activity. Raftopoulou et al. (10) showed that PTEN inhibits cell migration through its C2 domain and dephosphorylates itself depending on its protein phosphatase activity. Freeman et al. (11) demonstrated that PTEN physically associates with p53 in the nucleus, which in turn stabilizes p53 and affects p53 protein levels and transcription activity. Recently, Okumura (12) reports that the PTEN C-terminal domain physically interacts with the oncogenic MSP58 protein and suppresses cell transformation induced by MSP58 expression, independent of its catalytically activity.To further understand the biological functions of PTEN, we undertook an unbiased approach by comparing gene expression profiles of a Pten Ϫ/Ϫ mouse embryonic fibroblast (MEF) cell line with that of its isogenic counterpart (11, 13) using microarray technology. Among genes that are differentially expressed in these cell lines, we found that pleiotrophin (Ptn) was up-regulated in the Pten Ϫ/Ϫ MEFs as well as mammary tumor tissues of Pten conditional knock-out mice (14). Further experiments indicated that the expression of Ptn was regulated by the PI3K pathway, and Ptn overexpression contributes to tumorigenesis caused by PTEN loss. Microarray Analysis-Mouse cDNA microarrays containing 8,928 elements were printed by the UCLA Microarray Core Facility. Total RNA was isolated using TRIzol reagent (Invitrogen) according to the manufacturer's instructions. MATERIALS AND METHODS Cell Culture and Generation of Immortalized Fibroblasts-Fibro-For probe labeling and microarray hybridization, a protocol published by Xiang et al. (15) was adopted with minor modifications. Briefly, cDNA probes that incorporate aminoallyl-dUTP (aa-dUTP; Sigma) were synthesized...

This randomized controlled study aimed to evaluate whether adding bismuth to the standard first-line triple therapy could improve the eradication rate of Helicobacter pylori. A total of 162 patients with Helicobacter pylori infection were randomly assigned to either the 7-day triple therapy group (RAK regimen: rabeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg bid; n = 81) or the bismuth plus triple therapy group (n = 81). In the RBAK group, bismuth subcitrate 360 mg twice daily was added to the RAK regimen. A follow-up endoscopy or urea breath test was performed at least 4 weeks after eradication to confirm the treatment efficacy. Comparable compliance and Helicobacter pylori eradication rates were observed in both groups in either intention-to-treat [RAK 72.8% (59/81) versus RBAK 77.8% (63/81); p = 0.47] or per protocol analysis [RAK 74.7% (59/79) versus RBAK 81.8% (63/77); p = 0.26]. Adverse effects were commonly reported (50.6% for both groups) although most of these did not cause cessation of treatment. The resistance rate was 27.2% for metronidazole and 12.3% for clarithromycin. Adding bismuth to the standard 7-day triple therapy did not substantially increase the eradication rate. Further study is needed clarifying whether extending the duration of RBAK regimen to 10–14 days can lead to a better result.