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Residual Cells (residual + cell)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Neuroendocrine transdifferentiation induced by VPA is mediated by PPAR, activation and confers resistance to antiblastic therapy in prostate carcinoma

THE PROSTATE, Issue 6 2008
Adriano Angelucci
Abstract BACKGROUND Prostate cancer (PCa) is the most commonly diagnosed cancer in men in the Western Countries. When prostatectomy fails to eradicate the primary tumor, PCa is generally refractory to all therapeutic approaches. Valproic acid (VPA) is a promising anticancer agent recently assigned to the class of histone deacetylase (HDAC) inhibitors. However molecular mechanisms underlying VPA action in PCa cells are largely unknown and further experimental validation to prove its potential application in clinic practice is needed. RESULTS In our study we show that VPA is a potent inducer of neuro-endocrine transdifferentiation (NET) in androgen receptor null PCa cells, both in vitro and in vivo. NET was an early event detectable through the expression of neuro-endocrine (NE) markers within 72 hr after VPA treatment and it was associated to a reduction in the overall cell proliferation. When we interrupted VPA treatment we observed the recovery in residual cells of the basal proliferation rate both in vitro and in a xenograft model. The NET process was related to Bcl-2 over-expression in non-NE PCa cells and to the activation of PPAR, in NE cells. The use of specific PPAR, antagonist was able to reduce significantly the expression of NE markers induced by VPA. CONCLUSIONS Our data indicate that the use of VPA as monotherapy in PCa has to be considered with extreme caution, since it may induce an unfavorable NET. In order to counteract the VPA-induced NET, the inhibition of PPAR, may represent a suitable adjuvant treatment strategy and awaits further experimental validation. Prostate 68: 588,598, 2008. © 2008 Wiley-Liss, Inc. [source]

Immunocompetent T-Cells with a Memory-Like Phenotype are the Dominant Cell Type Following Antibody-Mediated T-Cell Depletion

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2005
Jonathan P. Pearl
T-cell depletion facilitates reduced immunosuppression following organ transplantation and has been suggested to be pro-tolerant. However, the characteristics of post-depletional T cells have not been evaluated as they relate to tolerance induction. We therefore studied patients undergoing profound T-cell depletion with alemtuzumab or rabbit anti-thymocyte globulin following renal transplantation, evaluating the phenotype and functional characteristics of their residual cells. Naïve T cells and T cells with potential regulatory function (CD4+CD25+) were not prevalent following aggressive depletion. Rather, post-depletion T cells were of a single phenotype (CD3+CD4+CD45RA-CD62L-CCR7-) consistent with depletion-resistant effector memory T cells that expanded in the first month and were uniquely prevalent at the time of rejection. These cells were resistant to steroids, deoxyspergualin or sirolimus in vitro, but were calcineurin-inhibitor sensitive. These data demonstrate that therapeutic depletion begets a limited population of functional memory-like T cells that are easily suppressed with certain immunosuppressants, but cannot be considered uniquely pro-tolerant. [source]

Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion,

APMIS, Issue 11-12 2005
ERIC SANTONI-RUGIU
Although normally quiescent, the adult mammalian liver possesses a great capacity to regenerate after different types of injuries in order to restore the lost liver mass and ensure maintenance of the multiple liver functions. Major players in the regeneration process are mature residual cells, including hepatocytes, cholangiocytes and stromal cells. However, if the regenerative capacity of mature cells is impaired by liver-damaging agents, hepatic progenitor cells are activated and expand into the liver parenchyma. Upon transit amplification, the progenitor cells may generate new hepatocytes and biliary cells to restore liver homeostasis. In recent years, hepatic progenitor cells have been the subject of increasing interest due to their therapeutic potential in numerous liver diseases as alternative or supportive/complementary tools to liver transplantation. While the first investigations on hepatic progenitor cells have focused on their origin and phenotypic characterization, recent attention has focused on the influence of the hepatic microenvironment on their activation and proliferation. This microenvironment comprises the extracellular matrix, epithelial and non-epithelial resident liver cells, and recruited inflammatory cells as well as the variety of growth-modulating molecules produced and/or harboured by these elements. The cellular and molecular responses to different regenerative stimuli seem to depend on the injury inflicted and consequently on the molecular microenvironment created in the liver by a certain insult. This review will focus on molecular responses controlling activation and expansion of the hepatic progenitor cell niche, emphasizing similarities and differences in the microenvironments orchestrating regeneration by recruitment of progenitor cell populations or by replication of mature cells. [source]

Incomplete cellular depopulation may explain the high failure rate of bovine ureteric grafts

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 5 2008
J. I. Spark
Background: The aim was to assess the results of a decellularized bovine ureter graft (SynerGraft®) for complex venous access. Methods: Bovine ureter conduits were implanted in patients with a failed fistula or access graft in whom native vessels were unsuitable as conduits. Graft histories were obtained from all patients who had undergone this procedure at one institution. Failed grafts were explanted and subjected to histological examination. A sample of fresh bovine ureter was immunostained for galactose (,1 , 3) galactose (,-Gal). Results: Nine patients with a median age of 46 (range 25,70) years underwent complex venous access surgery between August 2004 and November 2006 using a SynerGraft®. Graft types included loop superficial femoral artery to stump of long saphenous vein (four patients), loop brachial artery to vein (two), brachial artery to axillary vein (two) and left axillary artery to innominate vein (one). Three grafts developed aneurysmal dilatation and two thrombosed. Histological assessment of the explanted bovine ureters revealed acute and chronic transmural inflammation. Immunostaining of fresh bovine ureter suggested residual cells and the xenoantigen ,-Gal. Conclusion: Graft failure with aneurysmal dilatation and thrombosis in complex arteriovenous conduits using bovine ureter may be due to residual xenoantigens. Copyright © 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]