LAMP3 (DC-LAMP, TSC403, CD208) was originally isolated as a gene specifically expressed in lung tissues. LAMP3 is located on a chromosome 3q segment that is frequently amplified in some human cancers, including uterine cervical cancer. Because two other members of the LAMP family of lysosomal membrane glycoproteins, LAMP1 and LAMP2, were previously implicated in potentially modulating the interaction of vascular endothelial and cancer cells, we hypothesized that LAMP3 might also play an important part in metastasis. To clarify the metastatic potential of LAMP3 in cervical cancers, we transfected a LAMP3 expression vector into a human uterine cervical cancer cell line, TCS. In an in vitro invasion assay, the migration of LAMP3-overexpressing TCS cells was significantly higher than in control TCS cells. In an in vivo metastasis assay, distant metastasis was detected in 9 of 11 LAMP3-overexpressing TCS cell-injected mice and in only 1 of 11 control mice. Histologic study showed that LAMP3-overexpressing cells readily invaded into the lymph-vascular space. In clinical samples, quantitative real-time reverse transcription-PCR (RT-PCR) analyses showed that LAMP3 mRNA was significantly up-regulated in 47 of 47 (100%) cervical cancers and in 2 of 15 (13%) cervical intraepithelial neoplasias, compared with a low level of LAMP3 mRNA expressed in normal uterine cervixes. Interestingly, high LAMP3 expression was significantly correlated with the overall survival of patients with stage I/II cervical cancers. These findings indicate that LAMP3 overexpression is associated with an enhanced metastatic potential and may be a prognostic factor for cervical cancer. (Cancer Res 2005; 65(19): 8640-5)

Infectious acute gastroenteritis is an important public health problem worldwide. A total of 639 stool specimens were tested for the presence of diarrhea pathogens. The specimens were from outpatients with acute gastroenteritis who consulted the pediatric clinic in Kumamoto Prefecture, Japan, from June 2002 to December 2007. Of these, 421 (65.9%) were positive for diarrhea pathogens. Among them were norovirus (NoV) in 260 (61.8%), sapovirus (SaV) in 81 (19.2%), rotavirus in 49 (11.6%), adenovirus in 19 (4.5%), enterovirus in 13 (3.1%), astrovirus in 9 (2.1%), kobuvirus in 1 (0.2%), and bacterial pathogens in 11 (2.6%). Mixed infection (co-infection of viruses) was found in 22 (5.2%) of the 421 pathogen-positive stool samples. NoV was the most prevalent pathogen throughout the study period; however, the SaV detection rate was unexpectedly high and was found to be the secondary pathogen from 2005 to 2007. Genetic analysis of SaV with 81 strains demonstrated that SaV strains belonging to genogroup IV emerged in 2007, and dynamic genogroup changes occurred in a restricted geographic area. This study showed that SaV infection is not as rare as thought previously.

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A large variety of human tumours manifest a heterozygous or homozygous deletion in the 9p21 chromosome region. The list includes malignant melanoma, glioma, lung, bladder, pancreatic and renal cancers (Kamb et al, 1994;Nobori et al, 1994), as well as gynaecological tumours (reviewed by Wong et al, 1997). Two putative tumour suppressor genes have been identified in this region: p16 (also known as p16 INK4A , cyclin-dependent kinase 4 inhibitor, CDK4I, CDKN2, and MTS1), and p15 (p15 INK4B ).The p16 gene makes two different proteins, p16 and p19 ARF (p19 alternative reading frame), using different overlapping reading frames, starting with different first exons. The p16 protein uses exon 1α, and p19 ARF uses exon 1β; these two exons are alternatively spliced to the same second and third exons. The p16 and p15 proteins belong to a family of negative regulators of the cell cycle. Specific binding of p16 protein to the CDK4 or CDK6 cyclindependent protein kinases inhibits the phosphorylation activity of CDK-cyclin D complexes towards the nuclear RB/E2F protein complex (Serrano et al, 1993). p16 normally prevents phosphorylation of RB, resulting in RB's retention of E2F. Failure to release E2F at the late G1 checkpoint blocks the cell from entering the S phase (Hengstschläger et al, 1996;Lukas et al, 1996). The p19 ARF protein, although it has an unrelated amino acid sequence, has cell cycle arresting functions. It is the p16 protein that now appears to be the major target of mutations and deletions at the 9p21 loci.The p15 (MTS2) putative tumour suppressor gene is located 25 kb centromeric of the p16 gene on 9p. p15 contains sequences highly homologous to exon 2 of p16 and, like p16, inhibits both CDK4 and CDK6 kinase activities (Guan et al, 1994;Hannon and Beach, 1994). Homozygous deletions of p15 and hypermethylation-associated loss of p15 expression have been reported in glioblastomas (Jen et al, 1994).The p16/p19 ARF and p15 genes appear to play variably important roles in human tumorigenesis, with critical tissue specificities and uncertain implications for clinical prognoses. Little is currently known about the potential role of these genes in reproductive tract biology, and specifically in uterine tumours. We have begun to examine the expression of the p16 gene at the level of mRNA and protein, the methylation status of the 5′-CpG island of p16 exon 1α, and for p16 point mutations and homozygous deletions in these tumours. We have also analysed the p15 gene for mutations and homozygous deletions. We report that the inactivation of the p16 gene, either by homozygous gene deletion, mutation or loss of protein expression, occurs in a small but significant subset of these uterine tumours. Summary The roles of the p16 and p15 inhibitor of cyclin-dependent kinase tumour suppressor genes were examined in human uterine cervical and endometrial cancers. p16 mRNA, examined by reverse transcription polymerase chain reaction (RT-PCR), was significantly reduced in five of 19 (26%) cervical and four of 25 (16%) endometrial tu...

BackgroundIntestinal metaplasia (IM) is regarded as a premalignant lesion. However, endoscopic diagnosis of IM has been considered difficult. Using endoscopy, we found a unique pattern of erythema, “Mottled Patchy Erythema (MPE),” which includes severe IM. Helicobacter pylori (Hp) infection itself can cause erythema, which reflects histologic changes in the gastric mucosa. Therefore we enrolled Hp eradication patients to validate the relation between MPE and pathologic findings.MethodsWe enrolled patients with chronic gastritis who underwent successful Hp eradication at least 6 months before the study. We defined MPE as multiple flat or depressed erythematous lesions. When encountering MPE on endoscopy, we performed biopsy on both the MPE site and non-MPE site. The non-MPE site was defined as an adjacent mucosa located within 3 cm of the MPE site. All biopsy specimens were evaluated immunohistochemically for IM subtype using MUC2, MUC5AC, MUC6, CD10, and CDX2 stains. The degree of IM was defined according to the Updated Sydney System. The diagnostic accuracy of the MPE findings for pathologic IM was calculated. The relation between MPE and IM subtype was also assessed.ResultsA total of 102 patients were selected for the study. Of these, 55 (54%) patients had MPE. Biopsy specimens were taken from the MPE sites and non-MPE sites from these 55 patients. The IM percentages and median scores of IM were both significantly higher at the MPE sites (P < 0.001) than at the non-MPE sites. The sensitivity and specificity for MPE in the detection of histologic IM were 72.7% and 84.1%, respectively. No significant associations were observed in the expression of MUC2, MUC5AC, MUC6, CD10, and CDX2 between the MPE sites and non-MPE sites. There were no significant differences in the ratios (complete/incomplete) of IM subtypes between the two groups.ConclusionsMPE is a useful endoscopic finding to detect histologic IM without the use of chromoendoscopy and magnifying endoscopy. However, the IM subtype is difficult to identify. In the era of Hp eradication, MPE has the potential to become a predictive finding for the risk of gastric cancer.