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Background. Rapamycin is a potent immunosuppressive drug with proven efficacy in rejection prophylaxis in solid organ transplantation. By virtue of its immunosuppressive properties, rapamycin might also be useful in the treatment of autoimmune diseases. The aim of this study was to determine the effect of rapamycin on the severity of established nephritis in lupus-prone New Zealand Black/White F1 (NZB/W F1) mice. Methods. Six-month-old female NZB/W F1 mice with active nephritis (albuminuria >100 mg/dL) were treated with rapamycin (3 mg/kg body weight) or saline once daily by oral gavage for 4 months. The effect of rapamycin on the severity of nephritis was evaluated by clinical manifestations, biochemical parameters, renal histology, immunohistochemistry and semi-quantitative gene expression studies. Results. Treatment with rapamycin significantly decreased albuminuria, improved survival, diminished splenomegaly, preserved renal function and reduced serum anti-dsDNA antibody levels. Kidney sections from saline-treated mice revealed marked mesangial proliferation, tubular dilation with intra-tubular protein cast deposition and leukocytic infiltration of the interstitium. The rapamycin-treated mice, in contrast, had relatively mild histological changes in their kidneys. Rapamycin treatment also significantly reduced the amount of immune complex deposition in the glomeruli, suppressed the interstitial infiltration by T-cells, B-cells and macrophages as well as down-regulated the intra-renal expression of RANTES. Conclusions. We conclude that rapamycin is effective in attenuating the severity of established nephritis in NZB/W F1 mice. The beneficial effects of rapamycin are mediated, at least in part, through inhibition of lymphoproliferation, reduced RANTES expression and decreased inflammatory cell infiltration in the kidneys. Rapamycin could be of therapeutic value in the treatment of human lupus nephritis. [ABSTRACT FROM AUTHOR]

TWIST, a helix-loop-helix transcription factor, is highly expressed in many types of human cancer. We have previously found that TWIST confers prostate cancer cells with an enhanced metastatic potential through promoting epithelial–mesenchymal transition (EMT) and a high TWIST expression in human prostate cancer is associated with an increased metastatic potential. The predilection of prostate cancer cells to metastasize to bone may be due to two interplaying mechanisms (i) by increasing the rate of bone remodeling and (ii) by undergoing osteomimicry. We further studied the role of TWIST in promoting prostate cancer to bone metastasis. TWIST expression in PC3, a metastatic prostate cancer cell line, was silenced by small interfering RNA and we found that conditioned medium from PC3 with lower TWIST expression had a lower activity on stimulating osteoclast differentiation and higher activity on stimulating osteoblast mineralization. In addition, we found that these effects were, at least partly, associated with TWIST-induced expression of dickkopf homolog 1 (DKK-1), a factor that promotes osteolytic metastasis. We also examined TWIST and RUNX2 expressions during osteogenic induction of an organ-confined prostate cancer cell, 22Rv1. We observed increased TWIST and RUNX2 expressions upon osteogenic induction and downregulation of TWIST through short hairpin RNA reduced the induction level of RUNX2. In summary, our results suggest that, in addition to EMT, TWIST may also promote prostate cancer to bone metastasis by modulating prostate cancer cell-mediated bone remodeling via regulating the expression of a secretory factor, DKK-1, and enhancing osteomimicry of prostate cancer cells, probably, via RUNX2. [ABSTRACT FROM AUTHOR]

The article presents a microscopic image of a hepatocellular carcinoma. Its component cells can give cytological variations such as pleomorphic giant cells, clear cells, sarcomatoid change, fatty vacuolation and hyaline inclusion. This hepatocellular carcinoma was taken from a 75-year-old chronic hepatitis B carrier.

Presents a diagnostic image showing ectopic embryo in a glomerular mesangium in a 33-year-old man, an intravenous drug addict who was admitted for infective endocarditis and deteriorating renal function. Biopsy which revealed features of postinfectious glomerulonephritis; Search for subepithelial 'humps' in the electron photomicrographs.

Presents an image of the glomerular capillary lumen of an 11-year-old boy with hearing loss. Investigation of his hematuria and proteinuria; Discovery of Pinocchio taking the disguise of a neutrophil; Diagnosis of Alport's syndrome in the patient.

Urine from kidney transplant recipient has proven to be a viable source for donor DNA. However, an optimized protocol would be required to determine mis-matched donor HLA specificities in view of the scarcity of DNA obtained in some cases.In this study, fresh early morning urine specimens were obtained from 155 kidney transplant recipients with known donor HLA phenotype. DNA was extracted and typing of HLA-A, B and DRB1 loci by polymerase chain reaction-specific sequence primers was performed using tailor-made condition according to the concentration of extracted DNA.HLA typing of DNA extracted from urine revealed both recipient and donor HLA phenotypes, allowing the deduction of the unknown donor HLA and hence the degree of HLA mis-match. By adopting the modified procedures, mis-matched donor HLA phenotypes were successfully deduced in all of 35 tested urine samples at DNA quantities spanning the range of 620-24,000 ng.This urine-based method offers a promising and reliable non-invasive means for the identification of mis-matched donor HLA antigens in kidney transplant recipients with unknown donor HLA phenotype or otherwise inadequate donor information.

Inhibition of the PI3K (phosphoinositide 3-kinase)/Akt/mTORC1 (mammalian target of rapamycin complex 1) and Ras/MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase]/ERK pathways for cancer therapy has been pursued for over a decade with limited success. Emerging data have indicated that only discrete subsets of cancer patients have favourable responses to these inhibitors. This is due to genetic mutations that confer drug insensitivity and compensatory mechanisms. Therefore understanding of the feedback mechanisms that occur with respect to specific genetic mutations may aid identification of novel biomarkers that predict patient response. In the present paper, we show that feedback between the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways is cell-line-specific and highly dependent on the activating mutation of K-Ras or overexpression c-Met. We found that cell lines exhibited differential signalling and apoptotic responses to PD184352, a specific MEK inhibitor, and PI103, a second-generation class I PI3K inhibitor. We reveal that feedback from the PI3K/Akt/mTORC1 to the Ras/MEK/ERK pathway is present in cancer cells harbouring either K-Ras activating mutations or amplification of c-Met but not the wild-type counterparts. Moreover, we demonstrate that inhibition of protein phosphatase activity by OA (okadaic acid) restored PI103-mediated feedback in wild-type cells. Together, our results demonstrate a novel mechanism for feedback between the PI3K/Akt/mTORC1 and the Ras/MEK/ERK pathways that only occurs in K-Ras mutant and c-Met amplified cells but not the isogenic wild-type cells through a mechanism that may involve inhibition of a specific endogenous phosphatase(s) activity. We conclude that monitoring K-Ras and c-Met status are important biomarkers for determining the efficacy of PI103 and other PI3K/Akt inhibitors in cancer therapy.

Tumor-initiating cells (TIC), also known as cancer stem cells, are regarded widely as a specific subpopulation of cells needed for cancer initiation and progression. TICs have yet to be identified in esophageal tumors that have an increasing incidence in developed countries. Here, we report a CD90+ cell population found in esophageal squamous cell carcinoma (ESCC), which is endowed with stem cell--like properties and high tumorigenic and metastatic potential. mRNA profiling of these cells suggested pathways through which they drive tumor growth and metastasis, with deregulation of an Ets-1/MMP signaling pathway and epithelial--mesenchymal transition figuring prominently. These cells possessed higher self-renewal activity and were sufficient for tumor growth, differentiation, metastasis, and chemotherapeutic resistance. CD90+ TICs were isolated and characterized from ESCC clinical specimens as well as ESCC cell lines. In freshly resected clinical specimens, they represented a rare cell population, the levels of which correlated with strong family histories and lymph node metastasis. Our results prompt further study of this CD90+ population of esophageal TICs as potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background. Although lamivudine is effective for treatment of chronic hepatitis B (HBV) infection, its potential therapeutic impact on HBV-related membranous nephropathy (MN) in adults has not been characterized. Methods. We treated 10 HBsAg-positive patients with biopsy-proven MN, elevated serum alanine aminotransferase (ALT), and HBV-DNAemia (group 1), and compared their clinical course with 12 patients diagnosed to have HBV infection, elevated serum ALT, and MN in the pre-lamivudine era (group 2). Results. Baseline demographic and clinical parameters were not different between the 2 groups. In group 1, lamivudine treatment was associated with significant reduction in proteinuria, increase in serum albumin, normalization of ALT levels, and disappearance of circulating HBV-DNA during the first year. Four (40%) and 6 (60%) patients went into complete remission (proteinuria <0.3 g/d) at 6 and 12 months, respectively. In group 2, significant proteinuria persisted during the first year. One (8.3%) and 3 (25%) patients went into remission. Cumulative 3-year renal survival [using end-stage renal disease (ESRD) as primary end point] was 100% in group 1 and 58% in group 2 ( P= 0.024, log rank test). Blood pressure control reached the target of below 130/85 mm Hg in both groups. Lamivudine was well tolerated and not associated with any adverse events. Hepatic decompensation or malignancy was not observed during follow-up in both groups. Conclusion. HBV-related MN leads to ESRD in a significant proportion of patients before the advent of antiviral therapy. Lamivudine treatment improves renal outcome in HBV carriers with MN and evidence of liver disease. [ABSTRACT FROM AUTHOR]

Focuses on a study which revealed the role of albumin in the stimulation of interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo. Methods; Results; Discussion and summary.

Presents a quiz on the diagnosis of renal impairment after bone marrow transplantation. Background of the case; Vital signs after a year from the transplantation; Characteristics of bone marrow transplant nephropathy.