Magnetic Resonance Elastography to Assess Fibrosis in Kidney Allografts.

Background And Objectives: Fibrosis is a major cause of kidney allograft injury. Currently, the only means of assessing allograft fibrosis is by biopsy, an invasive procedure that samples <1% of the kidney. We examined whether magnetic resonance elastography, an imaging-based measure of organ stiffness, could noninvasively estimate allograft fibrosis and predict progression of allograft dysfunction.

The role of thrombectomy and diffusion-weighted imaging with MRI in post-transplant renal vein thrombosis: a case report.

Background: Surgical thrombectomy in the context of acute renal vein thrombosis (RVT) post-transplantation has had limited success, with considerable variation in the surgical techniques used. Unfortunately, it is usually followed by allograft nephrectomy within a few days if rapid allograft recovery does not ensue. We report a case of acute RVT in which nephrectomy was not performed despite a prolonged requirement for dialysis post-thrombectomy, but with recovery of renal function 2 weeks later.

A clinical and pathological variant of acute transplant glomerulopathy.

Acute transplant glomerulopathy transplant glomerulopathy (TG) is a common cause of late renal allograft loss. We describe a unique case of a renal transplant recipient who developed rapid-onset nephrotic-range proteinuria and acute kidney injury secondary to C4d negative acute TG. Two courses of intravenous Rituximab resulted in significant improvement in proteinuria and allograft function.

Injurious mechanical ventilation causes kidney apoptosis and dysfunction during sepsis but not after intra-tracheal acid instillation: an experimental study.

Background: Intratracheal aspiration and sepsis are leading causes of acute lung injury that frequently necessitate mechanical ventilation (MV), which may aggravate lung injury thereby potentially increasing the risk of acute kidney injury (AKI). We compared the effects of ventilation strategies and underlying conditions on the development of AKI.

Methods: Spraque Dawley rats were challenged by intratracheal acid instillation or 24 h of abdominal sepsis, followed by MV with a low tidal volume (LVT) and 5 cm H2O positive end-expiratory pressure (PEEP) or a high tidal volume (HVT) and no PEEP, which is known to cause more lung injury after acid instillation than in sepsis.

Digital pathology: Attitudes and practices in the Canadian pathology community.

Digital pathology is a rapidly evolving niche in the world of pathology and is likely to increase in popularity as technology improves. We performed a questionnaire for pathologists and pathology residents across Canada, in order to determine their current experiences and attitudes towards digital pathology; which modalities digital pathology is best suited for; and to assess the need for training in digital pathology amongst pathology residents and staff. An online survey consisting of 24 yes/no, multiple choice and free text questions regarding digital pathology was sent out via E-mail to all members of the Canadian Association of Pathologists and pathology residents across Canada.

Neuropilin-1 is expressed by breast cancer stem-like cells and is linked to NF-κB activation and tumor sphere formation.

Cancer stem cells (CSCs) initiate tumors and have a high resistance to conventional cancer therapy. Tranilast is an orally active drug of low toxicity that exerts inhibitory effects on breast CSCs. This appears to depend on its aryl hydrocarbon receptor (AHR) agonistic activity, but this receptor has diverse functions and it is unclear how CSCs are inhibited.

High tidal volume mechanical ventilation-induced lung injury in rats is greater after acid instillation than after sepsis-induced acute lung injury, but does not increase systemic inflammation: an experimental study.

Background: To examine whether acute lung injury from direct and indirect origins differ in susceptibility to ventilator-induced lung injury (VILI) and resultant systemic inflammatory responses.

Methods: Rats were challenged by acid instillation or 24 h of sepsis induced by cecal ligation and puncture, followed by mechanical ventilation (MV) with either a low tidal volume (Vt) of 6 mL/kg and 5 cm H2O positive end-expiratory pressure (PEEP; LVt acid, LVt sepsis) or with a high Vt of 15 mL/kg and no PEEP (HVt acid, HVt sepsis). Rats sacrificed immediately after acid instillation and non-ventilated septic animals served as controls.

A two-locus system controls susceptibility to colitis-associated colon cancer in mice.

We have previously shown that the differential susceptibility of A/J (susceptible) and C57BL/6J (B6, resistant) mouse strains to azoxymethane (AOM)-induced colorectal cancer (CRC) is controlled by the chromosome 3 locus, Ccs3. We report that A/J and B6 mice also show differential susceptibility to colitis-associated colorectal cancer (CA-CRC) induced by combined administration of AOM and dextran sulfate. This differential susceptibility is not controlled by Ccs3, but is under distinct genetic control.

Breast cancer stem-like cells are inhibited by a non-toxic aryl hydrocarbon receptor agonist.

Background: Cancer stem cells (CSCs) have increased resistance to cancer chemotherapy. They can be enriched as drug-surviving CSCs (D-CSCs) by growth with chemotherapeutic drugs, and/or by sorting of cells expressing CSC markers such as aldehyde dehydrogenase-1 (ALDH). CSCs form colonies in agar, mammospheres in low-adherence cultures, and tumors following xenotransplantation in Scid mice.

Tranilast treatment decreases cell growth, migration and inhibits colony formation of human breast cancer cells.

In the treatment of breast cancer, although a wide of choice of drugs and treatment modalities are available, drug resistance or drug toxicity poses a considerable challenge. Tranilast is a well tolerated drug used in the treatment of allergic disorders. Previous works in various models have shown that tranilast has the potential to be used as an anti-cancer drug.

Tranilast inhibits cell proliferation and migration and promotes apoptosis in murine breast cancer.

The malignant transformation of breast epithelium involves a number of cellular pathways, including those dependent on signaling from TGF beta. Tranilast [N-(3, 4-dimethoxycinnamonyl)-anthranilic acid] is a drug that is used in Japan to control allergic disorders in patients, and its mechanism of action involves TGF beta. In view of the multiple roles of TGF beta in tumor progression, we hypothesized in this study that tranilast impacts cell proliferation, apoptosis, and migration.

Hypocomplementaemic immune complex tubulointerstitial nephritis.

We report a rare cause of rapidly progressive renal failure associated with low complement, positive ANA but negative anti DS-DNA. A renal biopsy demonstrated tubulointerstitial nephritis with positive immunoglobulin staining involving the interstitium and tubular basement membrane but glomerular sparing. A review of the literature and differential diagnosis are discussed.

Tranilast inhibits the growth and metastasis of mammary carcinoma.

Tranilast (N-[3,4-dimethoxycinnamonyl]-anthranilic acid) is a drug of low toxicity that is orally administered, and has been used clinically in Japan as an antiallergic and antifibrotic agent. Its antifibrotic effect is thought to depend on the inhibition of transforming growth factor-beta (TGF-beta). It has also been shown to exert antitumor effects, but its mode of action is unclear.

Glypican-3 is overexpressed in lung squamous cell carcinoma, but not in adenocarcinoma.

Glypican-3 is a membrane-bound proteoglycan whose expression has been linked to malignancies through the existence of both mutations and aberrant protein expression. Reports on glypican-3 expression in lung cancer were limited, with some evidence for loss of expression, which suggested a tumor-suppressor role. We sought to evaluate glypican-3 expression in lung cancer at the protein and mRNA levels and correlate it with clinical, histological and genomic characteristics such as RAS mutation status.

Soluble CD44 secretion contributes to the acquisition of aggressive tumor phenotype in human colon cancer cells.

CD44, a widely distributed cell surface glycoprotein and a receptor for hyaluronan (HA), has been implicated in facilitating tumor growth and metastasis, antiapoptosis and directional motility of cancer cells. In order to investigate the role of soluble CD44 (CD44(sol)) in colon cancer cell growth, SW620, a human colon cancer cell line deficient in CD44 expression was stably transfected with human CD44 cDNA containing exons 1-5, 15 and 16 of the human CD44. Western blot analyses demonstrated the presence of 78 kDa soluble CD44 protein in the culture supernatant of stably transfected cell lines (CD44(sol) clones) and were not detected in the empty vector control line (clone m).

Suppression of human colon cancer tumors in nude mice by siRNA CD44 gene therapy.

The expression of CD44, an adhesion protein associated with the tumor stem cell phenotype, is increased in most human malignant neoplasms. To further delineate the role of CD44 in colon cancer, we inhibited its expression using the siRNA method. HT-29, a human colon cancer cell line producing a large amount of CD44, was transfected with a construct producing a siRNA targeting a 19 mer sequence of the transmembrane domain of CD44 spanning between exon 16 and 17.

CD44 regulates cell migration in human colon cancer cells via Lyn kinase and AKT phosphorylation.

Colon cancer is among the leading causes of cancer death in North America. CD44, an adhesion and antiapoptotic molecule is overexpressed in colon cancer. Cofilin is involved in the directional motility of cells.

Glypican-3 expression in hepatocellular tumors: diagnostic value for preneoplastic lesions and hepatocellular carcinomas.

Glypican-3 (GPC3), a member of heparan sulfate proteoglycans, plays a role in cell growth, differentiation, and migration. The objectives of this study were to assess the diagnostic value of GPC3 immunostaining in hepatocellular carcinomas (HCCs) and to analyze its expression profile in preneoplastic lesions. Tissue microarrays were built by sampling 54 HCCs and adjacent liver tissues (21 developing from cirrhosis and 33 from normal liver) and 94 cirrhotic macronodules.

Loss of the tumor suppressor Vhlh leads to upregulation of Cxcr4 and rapidly progressive glomerulonephritis in mice.

Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome characterized by loss of renal function within days to weeks and by glomerular crescents on biopsy. The pathogenesis of this disease is unclear, but circulating factors are believed to have a major role. Here, we show that deletion of the Von Hippel-Lindau gene (Vhlh) from intrinsic glomerular cells of mice is sufficient to initiate a necrotizing crescentic glomerulonephritis and the clinical features that accompany RPGN.

Grg1 acts as a lung-specific oncogene in a transgenic mouse model.

Groucho proteins are transcriptional corepressors that are recruited to gene regulatory regions by numerous transcription factors. Long isoforms, such as Grg1, have all the domains of the prototype Drosophila Groucho. Short Groucho proteins, such as Grg5, have only the amino-terminal Q and G/P domains.