Human polyomavirus 7 (HPyV7) is one of 11 HPyVs recently discovered through genomic sequencing technologies. Two lung transplant recipients receiving immunosuppressive therapy developed pruritic, brown plaques on the trunk and extremities showing a distinctive epidermal hyperplasia with virus-laden keratinocytes containing densely packed 36-45-nm icosahedral capsids. Rolling circle amplification and gradient centrifugation testing were positive for encapsidated HPyV7 DNA in skin and peripheral blood specimens from both patients, and HPyV7 early and capsid proteins were abundantly expressed in affected tissues. We describe for the first time that HPyV7 is associated with novel pathogenicity in some immunosuppressed individuals.

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Colonic sessile serrated adenoma, in contrast to hyperplastic polyp, is thought to be related to sporadic colorectal cancers with high microsatellite instability. However, the morphological distinction between these entities is difficult and subject to observer and sampling variation. Therefore, we elected to investigate the expression of gastric mucin MUC6 as a potential marker to separate the two in the hope of finding an objective and reproducible adjunct to morphological diagnosis. Endoscopic biopsies of colonic polyps with serrated architecture, but without cytological dysplasia were studied and categorized as sessile serrated adenoma or hyperplastic polyp, using previously published morphological criteria. Smaller groups of serrated polyps with cytological dysplasia (traditional serrated adenomas, filiform serrated adenomas and sessile serrated adenomas with cytological dysplasia) were also included. In total, 94 polyps were immunohistochemically stained with antibodies to MUC6 and to MLH-1. MUC6 was found to have 100% specificity in distinguishing sessile serrated adenoma (N ¼ 26; positive staining) from hyperplastic polyp (N ¼ 48; negative staining). Traditional serrated adenomas and filiform serrated adenomas were also negative for MUC6. Sessile serrated adenomas with cytological dysplasia were found to lose expression of MLH-1 in dysplastic areas, while retaining MUC6 expression. Neither anatomic location in the right or left colon nor polyp size appears to account for the differences in MUC6 expression.

Cumulative methotrexate doses up to 5410 mg given up to 281 wk in patients with inflammatory bowel disease are associated with little hepatotoxicity. Surveillance liver biopsies based on cumulative methotrexate doses are not warranted in these patients.

Gastrointestinal stromal tumors (GIST) are caused by activating mutations in the KIT or PDGFRA receptor tyrosine kinase genes. Although >85% of GIST patients treated with the small-molecule inhibitor imatinib mesylate (Gleevec) achieve disease stabilization, complete remissions are rare and a substantial proportion of patients develop resistance to imatinib over time. Upregulation of soluble, non-chromatin-bound histone H2AX has an important role in imatinib-induced apoptosis of GIST cells. Additionally, H2AX levels in untreated GIST are maintained at low levels by a pathway that involves KIT, phosphoinositide 3-kinase, and the ubiquitin-proteasome system. In this study, we asked whether bortezomib-mediated inhibition of the ubiquitinproteasome machinery could lead to upregulation of histone H2AX and GIST cell death. We show that bortezomib rapidly triggers apoptosis in GIST cells through a combination of mechanisms involving H2AX upregulation and loss of KIT protein expression. Downregulation of KIT transcription was an underlying mechanism for bortezomib-mediated inhibition of KIT expression. In contrast, the nuclear factor-κB signaling pathway did not seem to play a major role in bortezomib-induced GIST cell death. Significantly, we found that bortezomib would induce apoptosis in two imatinib-resistant GIST cell lines as well as a short-term culture established from a primary imatinib-resistant GIST. Collectively, our results provide a rationale to test the efficacy of bortezomib in GIST patients with imatinib-sensitive or -resistant tumors.