Metabolic skeletal disorders associated with impaired bone formation are a major clinical challenge. One approach to treat these defects is to silence bone-formation-inhibitory genes by small interference RNAs (siRNAs) in osteogenic-lineage cells that occupy the niche surrounding the bone-formation surfaces. We developed a targeting system involving dioleoyl trimethylammonium propane (DOTAP)-based cationic liposomes attached to six repetitive sequences of aspartate, serine, serine ((AspSerSer)(6)) for delivering siRNAs specifically to bone-formation surfaces. Using this system, we encapsulated an osteogenic siRNA that targets casein kinase-2 interacting protein-1 (encoded by Plekho1, also known as Plekho1). In vivo systemic delivery of Plekho1 siRNA in rats using our system resulted in the selective enrichment of the siRNAs in osteogenic cells and the subsequent depletion of Plekho1. A bioimaging analysis further showed that this approach markedly promoted bone formation, enhanced the bone micro-architecture and increased the bone mass in both healthy and osteoporotic rats. These results indicate (AspSerSer)(6)-liposome as a promising targeted delivery system for RNA interference-based bone anabolic therapy.

Loss of heterozygosity (LOH) at chromosome 3p21 is frequent in cervical cancers. The candidate tumor suppressor gene, RASSF1A located at 3p21.3, is found to be inactivated in several major human cancers, implicating its significance in carcinogenesis. We aimed to investigate the status of RASSF1A in cervical cancers. The mutation and methylation status of RASSF1A were analysed in 4 cervical cancer cell lines, 50 primary cervical cancers including 33 squamous cell carcinoma (SCC), 17 adenocarcinoma (AC) and 11 normal controls. The primary cancer samples were also detected for LOH at 3p21 and human papillomavirus (HPV Despite the success of nationwide cervical smear screening programs in many developed countries, cervical cancers remain one of the leading cancers of women worldwide. 1 Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are the 2 most common histologic types, accounting for about 70% and 20 -30% of all cervical cancers, respectively. 2 Human papilloma virus (HPV) infection with integration of the viral DNA into the host genome is a crucial step of carcinogenesis of cervical cancers. The E6 and E7 viral oncoproteins can bind to p53 and retinoblastoma gene products, respectively; interact with various cell cycle-related cellular proteins; and result in antitumor suppression or disruption of cell cycle checkpoints. 3-6 Although high-risk type HPVs are highly prevalent among cervical cancers, 7,8 only a small percentage of high-risk HPV-infected cases progress to malignancy, which are usually after a long latency period. 9,10 The rates of progression to in situ or invasive cervical carcinoma vary considerably among HPV-positive women. 11 Factors accounting for the long latency periods and genetic/epigenetic events governing the pace of progression have not been fully identified.Loss of heterozygosity is commonly found in cervical cancers at chromosome 3p, 6q, 11q and 17q. 12-17 3p21 and 3p14 are 2 of the most frequent deletion regions, implying that cervical cancerrelated tumor suppressor genes may be located at these sites.FHIT (fragile histidine triad) located at 3p14.2 has been implicated as a possible tumor suppressor gene. Interestingly, FHIT spans a fragile site FRA3B, which is a frequent region of HPV integration. 18 However, no significant differences in the prevalences of aberrant or truncated mRNA transcripts between cervical cancers and normal tissues were found. 17,19 Therefore, the role of FHIT gene in cervical carcinogenesis remains uncertain.Recently, increasing evidence has been gathered to support that RASSF1A located at 3p21.3 is a possible tumor suppressor gene. RASSF1A inactivation via promoter hypermethylation is commonly found in several types of human cancer cell lines as well as primary human cancer tissue samples. 20 -28 Although hypermethylation of RASSF1A is frequent, true loss-of-function mutations are only rarely detected. Moreover, hypermethylation of RASSF1A has been proven to result in silencing of the gene: As hypermethylation was highly correlated with loss of gene ...

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INTRODUCTIONCyclins, cyclin dependent kinases and their inhibitors regulate cell growth, differentiation, survival, and cell death. Gene abnormalities and aberrant expression of these cell cycle regulators play a pivotal role in the pathogenesis of cancers, including gastric cancer. 1 Cyclin D promotes progression through the G1 phase of the cell cycle by regulating the activity of CDK4 and CDK6. 2 Cyclin D1 expression in malignant lesions has been extensively studied. 3±5 Nonetheless, little is known about cyclin D2 expression in gastric cancer. Recently, Takano et al. showed that over-expression SUMMARY Background and aims: Cyclins and cyclin-dependent kinase inhibitors play a crucial role in the control of cell cycle transitions. Enhanced expression of cyclin D2 and reduced expression of p27 kip1 (p27) have been implicated in the pathogenesis of cancer. Because intestinal metaplasia has been regarded as a premalignant lesion, we investigated the expression of cyclin D2 and p27 in Helicobacter pylori-associated chronic gastritis with and without intestinal metaplasia, and followed the changes after H. pylori eradication. Methods: Expression of cyclin D2 and p27 was studied by immunohistochemistry in 59 patients (including 35 patients with intestinal metaplasia) and in 10 gastric cancer patients. Among them, 29 H. pylori-infected patients had serial gastric biopsies taken before and at 1-year after eradication of H. pylori. Results: Expression of cyclin D2 was signi®cantly higher in gastric cancers when compared to their adjacent