Vitamin D receptor upregulates tight junction protein claudin-5 against colitis-associated tumorigenesis.

Tight junctions are essential for barrier integrity, inflammation, and cancer. Vitamin D and the vitamin D receptor (VDR) play important roles in colorectal cancer (CRC). Using the human CRC database, we found colonic VDR expression was low and significantly correlated with a reduction of Claudin-5 mRNA and protein.

Use of an Over-the-Scope Clip for Closure of an Iatrogenic Nephrocolic Fistula Resulting From Cryoablative Therapy for Renal Cell Cancer of a Transplanted Renal Graft.

Although uncommon, cryoablation of tumors can result in collateral damage to adjacent organs resulting in difficult-to-treat perforation and fistulization. Full-thickness closure of defects has been described with the use of over-the-scope clips. We describe the case of a 56-year-old woman who underwent cryoablation of renal cell carcinoma of her transplanted kidney that was complicated by cryoinjury to her sigmoid colon with subsequent nephrocolic fistula and abscess formation resistant to conservative treatment.

Theranostic Gastrointestinal Endoscopy: Bringing Healing Light to the Lumen.

Current conventional endoscopes have restricted the accuracy of treatment delivery and monitoring. Over the past decade, there have been major developments in nanotechnology and light triggered therapy, potentially allowing a better detection of challenging lesions and targeted treatment of malignancies in the gastrointestinal tract. Theranostics is a developing form of personalized medicine because it combines diagnosis and targeted treatment delivered in one step using advances in nanotechnology.

Off-Label Teduglutide Therapy in Non-intestinal Failure Patients with Chronic Malabsorption.

Background: Teduglutide, a glucagon-like peptide 2 analog, has demonstrated efficacy in treating adult patients with short bowel syndrome (SBS) and dependence on parenteral nutrition (PN), but its role in chronic malabsorptive states that do not necessitate PN remains uncertain.

Aims: To evaluate teduglutide use beyond its approved indications and to discuss the results of this adjunctive treatment in patients resistant to established therapy.

Results: This series reports four patients treated with teduglutide off-label.

Endoscopic Follow-up of Intestinal Transplant Recipients.

The growing population of intestinal transplant recipients present a unique challenge to the gastroenterologists responsible for their support and evaluation. Improvements in patient and graft survival are largely attributed to surgical advancements, refined antirejection therapy, and enhanced endoscopic surveillance protocols that better perceive rejection and other complications. This article reviews the endoscopic management and interventions provided for transplant recipients at the University of Illinois Hospital with complications, such as acute rejection, ischemia, bleeding, fistula, post-transplant lymphoproliferative disorder, and gastroparesis.

Management and Complications of Short Bowel Syndrome: an Updated Review.

Short bowel syndrome (SBS) is defined as loss of bowel mass from surgical resection, congenital defects, or disease. Intestinal failure (IF) includes the subset of SBS unable to meet nutrition needs with enteral supplements and requires parenteral nutrition (PN). The parenteral treatment of SBS is now a half-century old.

Disruption of the mouse protein tyrosine kinase 6 gene prevents STAT3 activation and confers resistance to azoxymethane.

Background & Aims: Protein tyrosine kinase 6 (PTK6) is expressed throughout the gastrointestinal tract and is a negative regulator of proliferation that promotes differentiation and DNA-damage-induced apoptosis in the small intestine. PTK6 is not expressed in normal mammary gland, but is induced in most human breast tumors. Signal transducer and activator of transcription 3 (STAT3) mediates pathogenesis of colon cancer and is a substrate of PTK6.

Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia.

Curcumin is derived from the spice tumeric and has antiinflammatory and antineoplastic effects in vitro and in animal models, including preventing aberrant crypt foci (ACF) and adenomas in murine models of colorectal carcinogenesis. Inhibiting the production of the procarcinogenic eicosanoids prostaglandin E₂ (PGE₂) and 5-hydroxyeicosatetraenoic acid (5-HETE) can suppress carcinogenesis in rodents. Curcumin reduces mucosal concentrations of PGE₂ (via inhibition of cyclooxygenases 1 and 2) and 5-HETE (via inhibition of 5-lipoxygenase) in rats.

Reduced susceptibility to azoxymethane-induced aberrant crypt foci formation and colon cancer in growth hormone deficient rats.

Objectives: To evaluate the role of GH in colon carcinogenesis, we examined the formation of aberrant crypt foci (ACFs) and tumor development in wild type (WT) and GH-deficient, spontaneous dwarf rats (SDRs) exposed to the carcinogen azoxymethane (AOM).

Design: ACF were quantified by stereomicroscopy and tumor number and weights were recorded for each animal. Cell proliferation was measured by vincristine metaphase arrest, flow cytometry, and bromodeoxyuridine (BrdU) incorporation.

Aberrant crypt focus size predicts distal polyp histopathology.

Aberrant crypt foci (ACF) are the earliest histopathologic lesion associated with colorectal cancer. ACFs are commonly used as a surrogate marker for colorectal cancer chemoprevention studies in rodents and, more recently, in humans. However, ACF prevalence in unselected populations is not known, nor which ACF features are important for predicting polyp histopathology.

Tethered capsule endoscopy, a low-cost and high-performance alternative technology for the screening of esophageal cancer and Barrett's esophagus.

Esophageal cancer is currently the fastest growing cancer in the United States. To help combat the recent rise in morbidity, our laboratory has developed a low-cost tethered capsule endoscope system (TCE) aimed at improving early detection of esophageal cancer. The TCE contains a resonant fiberoptic laser scanner (1.

Colon cancer chemoprevention by a novel NO chimera that shows anti-inflammatory and antiproliferative activity in vitro and in vivo.

Chemopreventive agents in colorectal cancer possess either antiproliferative or anti-inflammatory actions. Nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase-2 inhibitors have shown promise, but are compromised by side effects. Nitric oxide donor NSAIDs are organic nitrates conjugated via a labile linker to an NSAID, originally designed for use in pain relief, that have shown efficacy in colorectal cancer chemoprevention.

Genomic instability of human aberrant crypt foci measured by inter-(simple sequence repeat) PCR and array-CGH.

Aberrant crypt foci (ACF) are the earliest identifiable neoplastic lesions in the colon. Thirty-two ACFs were examined for genomic instability in forms detectable either by inter-(simple sequence repeat) PCR or by array comparative genomic hybridization [array-CGH]. One-fourth of ACFs revealed moderate instability by inter-(simple sequence repeat) PCR; none showed amplifications or deletions on array-CGH.

Aberrant crypt foci.

Colon cancer evolves through epithelial cell deregulation and inappropriate proliferation. These histopathological characteristics are exemplified in the biochemical, immunohistochemical, genetic and epigenetic elements detected within colonic mucosa. Early detection is paramount for the prevention of colon cancer deaths.

Allelic loss of the gene for the GPX1 selenium-containing protein is a common event in cancer.

Selenium has been shown to reduce cancer incidence in animal models and more recent data indicate that it may be protective in humans as well. However, little is known about the mechanism by which selenium prevents cancer. Cytosolic glutathione peroxidase (GPX1), a selenium-containing antioxidant enzyme, has been implicated in the development of cancer of the head and neck, lung, and breast, in part because of allelic loss at the GPX1 locus.

Expression of vitamin D receptor and 25-hydroxyvitamin D3-1{alpha}-hydroxylase in normal and malignant human colon.

Considerable evidence exists to support the use of vitamin D to prevent and/or treat colorectal cancer. However, the routine use of bioactive vitamin D, 1,25-dihydroxyvitamin D3, is limited by the side effect of toxic hypercalcemia. Recent studies, however, suggest that colonic epithelial cells express 25-hydroxyvitamin D3-1alpha-hydroxylase, an enzyme that converts nontoxic pro-vitamin D, 25-hydroxycholecalciferol [25(OH)D3], to its bioactive form.

Expression and membrane localization of MCT isoforms along the length of the human intestine.

Recent studies from our laboratory and others have demonstrated the involvement of monocarboxylate transporter (MCT)1 in the luminal uptake of short-chain fatty acids (SCFAs) in the human intestine. Functional studies from our laboratory previously demonstrated kinetically distinct SCFA transporters on the apical and basolateral membranes of human colonocytes. Although apical SCFA uptake is mediated by the MCT1 isoform, the molecular identity of the basolateral membrane SCFA transporter(s) and whether this transporter is encoded by another MCT isoform is not known.

Relationship of aging and tobacco use with the development of aberrant crypt foci in a predominantly African-American population.

Background And Aims: In clinical studies, diminished folate availability appears to increase the risk for colorectal neoplasms. Additionally, alcohol and tobacco use are associated with an increased risk for colon cancer, but the early pathologic events by which these agents promote neoplastic transformation are not well understood. Aberrant crypt foci (ACF) are potential precursors of adenoma and cancer, and can be visualized by magnification endoscopy.

Tumor suppressor functions for the Cdk inhibitor p21 in the mouse colon.

The Cdk inhibitor p21 regulates p53-mediated growth arrest following DNA damage. It is expressed during epithelial differentiation in a variety of organs including colon. We investigated susceptibility of p21-deficient mice to the colon carcinogen azoxymethane (AOM).

Increased frequency of gastrin-releasing peptide receptor gene mutations during colon-adenocarcinoma progression.

Epithelial cells lining the mature human colon do not normally express receptors for gastrin-releasing peptide (GRPR). In contrast, we have shown that when aberrantly expressed in functional form in colon cancer, this protein acted as a morphogen where it caused tumor cells to adopt a better-differentiated phenotype. Importantly, GRPR mRNA is ubiquitously mutated in human colon cancer cell lines, with inactivating mutations detected in all cell lines not expressing functional receptor.