Role of microRNAs in resveratrol-mediated mitigation of colitis-associated tumorigenesis in Apc(Min/+) mice.

The pleiotropic effects of resveratrol include anti-inflammatory, antioxidant, and anticancer activities, and thus unique possibilities exist to explore mechanistic pathways of chemoprevention. The aim of this study was to investigate the role of microRNA (miRNA) alterations induced by resveratrol in the context of chemopreventive mechanisms against dextran sodium sulfate (DSS)-induced colitis-associated tumorigenesis in the Apc(Min/+) mouse. To that end, Apc(Min/+) mice were exposed to 2% DSS to enhance intestinal inflammation and polyp development. Concurrently, mice received either vehicle or resveratrol treatment via oral gavage for 5 weeks. Interestingly, treatment of DSS-exposed mice with resveratrol resulted in decreased number and size of polyps, fewer histologic signs of cell damage, and decreased proliferating epithelial cells in intestinal mucosa compared with vehicle. Resveratrol treatment dramatically reversed the effects of DSS on the numbers of specific inflammatory CD4(+) T cells, CD8(+) T cells, B cells, natural killer T cells, and myeloid-derived suppressor cells in mesenteric lymph nodes. Resveratrol treatment also decreased interleukin-6 (IL-6) and tumor necrosis factor-α protein levels and reduced IL-6 and cyclooxygenase-2 mRNA expression. Microarray analysis revealed 104 miRNAs exhibiting >1.5-fold differences in expression in the intestinal tissue of resveratrol-treated mice. Among them, two miRNAs with anti-inflammatory properties, miRNA-101b and miRNA-455, were validated to be upregulated with resveratrol treatment by reverse-transcription polymerase chain reaction. Pathway analysis revealed that numerous differentially regulated miRNAs targeted mRNAs associated with inflammatory processes with known roles in intestinal tumorigenesis. These results suggest that resveratrol mediates anti-inflammatory properties and suppresses intestinal tumorigenesis through miRNA modulation.

Expression of CDK8 and CDK8-interacting Genes as Potential Biomarkers in Breast Cancer.

CDK8 and its paralog CDK19, in complex with CCNC, MED12 and MED13, are transcriptional regulators that mediate several carcinogenic pathways and the chemotherapy-induced tumor-supporting paracrine network. Following up on our previous observation that CDK8, CDK19 and CCNC RNA expression is associated with shorter relapse-free survival (RFS) in breast cancer, we now found by immunohistochemical analysis that CDK8/19 protein is overexpressed in invasive ductal carcinomas relative to non-malignant mammary tissues. Meta-analysis of transcriptomic data revealed that higher CDK8 expression is associated with shorter RFS in all molecular subtypes of breast cancer. These correlations were much stronger in patients who underwent systemic adjuvant therapy, suggesting that CDK8 impacts the failure of systemic therapy. The same associations were found for CDK19, CCNC and MED13. In contrast, MED12 showed the opposite association with a longer RFS. The expression levels of CDK8 in breast cancer samples were directly correlated with the expression of MYC, as well as CDK19, CCNC and MED13 but inversely correlated with MED12. CDK8, CDK19 and CCNC expression was strongly increased and MED12 expression was decreased in tumors with mutant p53. Gene amplification is the most frequent type of genetic alterations of CDK8, CDK19, CCNC and MED13 in breast cancers (9.7% of which have amplified MED13), whereas point mutations are more common in MED12. These results suggest that the expression of CDK8 and its interactive genes has a profound impact on the response to adjuvant therapy in breast cancer in accordance with the role of CDK8 in chemotherapy-induced tumor-supporting paracrine activities.

The evolution of an integrated ultrasound curriculum (iUSC) for medical students: 9-year experience.

Interest in ultrasound education in medical schools has increased dramatically in recent years as reflected in a marked increase in publications on the topic and growing attendance at international meetings on ultrasound education. In 2006, the University of South Carolina School of Medicine introduced an integrated ultrasound curriculum (iUSC) across all years of medical school. That curriculum has evolved significantly over the 9 years. A review of the curriculum is presented, including curricular content, methods of delivery of the content, student assessment, and program assessment. Lessons learned in implementing and expanding an integrated ultrasound curriculum are also presented as are thoughts on future directions of undergraduate ultrasound education. Ultrasound has proven to be a valuable active learning tool that can serve as a platform for integrating the medical student curriculum across many disciplines and clinical settings. It is also well-suited for a competency-based model of medical education. Students learn ultrasound well and have embraced it as an important component of their education and future practice of medicine. An international consensus conference on ultrasound education is recommended to help define the essential elements of ultrasound education globally to ensure ultrasound is taught and ultimately practiced to its full potential. Ultrasound has the potential to fundamentally change how we teach and practice medicine to the benefit of learners and patients across the globe.

Intramuscular low-grade myxoid neoplasm with recurrent potential (cellular myxoma) of the lower extremity: case report with cytohistologic correlation and review of the literature.

"Low-grade myxoid neoplasm with recurrent potential" (cellular myxoma) is a term recently used to describe a subset of soft tissue lesions with histology intermediate between intramuscular myxoma and low-grade myxofibrosarcoma or myxoid malignant fibrous histiocytoma (MFH), while resembling a deeper counterpart of superficial angiomyxoma. Their distinctive biological behavior is characterized by the potential to recur locally, in contrast to intramuscular myxoma, while having no potential to advance in grade or metastasize when compared to low-grade myxofibrosarcoma. We present a cytohistological correlation for an intramuscular location of such a tumor in the lower extremity of a 49-yr-old male.

Dendriform pulmonary ossification, a form of diffuse pulmonary ossification: report of a 26-year autopsy experience.

CONTEXT: Dendriform pulmonary ossification (DPO) is an uncommon form of diffuse pulmonary ossification that typically affects the pulmonary interstitium in a setting of interstitial fibrosis. OBJECTIVE: To determine the incidence and characteristics of DPO and correlate the clinical, radiographic, and pathologic features in order to better understand its pathogenesis and behavior and facilitate proper therapy. DESIGN: Adult autopsies performed at a tertiary care center from 1978 to 2004 were reviewed to identify cases of DPO. Clinical, radiographic, and pathologic findings, including ultrastructural studies in select cases, were analyzed and correlated. RESULTS: Eight cases of DPO were identified from 1393 adult autopsies. None of the cases was diagnosed antemortem. The prevalence of DPO was 0.5%, and the incidence was 0.28 cases per year. Most patients had a history of chronic lung disease, and all were 65 years of age or older. CONCLUSIONS: Dendriform pulmonary ossification is an uncommon and unusual entity seen incidentally at autopsy and associated with chronic lung disease. It is well demonstrated in postmortem examination, confirmed by microscopy and ultrastructural study, but rarely diagnosed and virtually never considered clinically. Clinical diagnoses include bronchiectasis and interstitial pneumonitis based on radiographic evidence. With its associated radiographic/pathologic findings, DPO should be considered in the differential diagnosis of chronic lung disease.