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PubMed2004

[The influence of hepatoprotector 2-ethylthiobenzimidazole hydrobromide (bemithyl) on the content of glycogen in cirrhotic rat liver hepatocytes located in various microenvironments].

Using absorption and fluorescent cytophotometry methods, glycogen contents were studied in hepatocytes located in liver lobules and in hepatocytes, which make the general population of these cells in normal and cirrhotic rat liver. In cirrhosis, the content of glycogen in hepatocytes located in lobules obviously rises in comparison with the norm, but to a lesser degree, than in hepatocytes making the general population of these cells in cirrhotic liver. The content of glycogen in hepatocytes, located in lobules of pathologically changed liver in bemithyl treated rats, did not differ from the norm. At the same time, the glycogen content in hepatocytes, representing the general population of these cells in cirrhotically altered bemithyl injected rat liver, remained higher than in the norm. The data obtained indicate that distinctions in particular cell microinvironment, obviously present in cirrhotic liver, render essential influence on hepatocyte functional activity.

Animals↗
PubMed2004

Overcoming immune resistance in the tumor microenvironment by blockade of indoleamine 2,3-dioxygenase and programmed death ligand 1.

The specificity of antitumor immunity continues to attract interest as a potentially powerful mode of cancer treatment. Cancer vaccines and adoptive T-cell infusion are strategies that can increase the frequency of circulating tumor antigen-specific T-cells. However, although these approaches can produce clinical responses in a minority of patients, tumor escape from immune destruction appears to dominate in many instances. Several molecular mediators of tumor resistance to immune effector cells have been identified that can be targeted pharmacologically. Two of these, the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase and the T-cell inhibitory programmed death ligand 1, are discussed in this review. Blockade of these molecules may increase the efficacy of tumor-specific T-cell therapies in cancer patients.

Animals↗
PubMed1992

Recombinant human interleukin-3 and recombinant human granulocyte-macrophage colony-stimulating factor administered in vivo after high-dose cyclophosphamide cancer chemotherapy: effect on hematopoiesis and microenvironment in human bone marrow.

The effects on bone marrow (BM) cell proliferation and differentiation of recombinant human interleukin-3 (rhIL-3) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) administered after high-dose (7 g/m2/d) cyclophosphamide (HD-CTX) chemotherapy were studied in nine patients with malignancies without BM involvement and in three control patients. rhIL-3 at a dose of 1 to 5 micrograms/kg/day was administered for 14 to 18 days by continuous intravenous (i.v.) infusion and rhGM-CSF was administered at a dose of 5.5 micrograms/kg/day for 14 days. Changes induced by cytokine treatment were assessed by morphoimmunohistochemical analysis of BM biopsies. Comparison was made in the cytokine-treated groups and with control patients who received HD-CTX alone. BM cellularity and the myeloid/erythroid (ME) ratio were lower in rhIL-3-treated than in rhGM-CSF-treated patients, but in both groups it was significantly higher than in the controls. The proportion of BM cells stained by PC10, a monoclonal antibody (MoAb) recognizing a proliferation-associated nuclear protein (PCNA), increased from 6.78% to 21.18% (P less than .02) after rhIL-3, and from 5% to 35.33% (P less than .001) after rhGM-CSF; no increase was observed in the control group. The frequency of CD34+ BM cells was unchanged after rhIL-3 (P = NS) and decreased after rhGM-CSF (P less than .001). In both groups, most of the PC10+ cells were represented by promyelocytes and myelocytes with no increase in blast cell numbers. rhIL-3-treated BM showed an increased number of megakaryocytes and increased proliferative activity of erythroid cells as compared with rhGM-CSF cases. BM stroma changes observed in both treated groups included endothelial cell proliferation, increased BM macrophage concentration, and increase in BM fibroblasts as detected with an anti-nerve growth factor receptor antibody. In most rhIL-3-treated cases, BM fibrosis developed after treatment. The same effect was not observed in rhGM-CSF patients.

Adult↗
PubMed2005

Rapid destruction of the tumor microenvironment by CTLs recognizing cancer-specific antigens cross-presented by stromal cells.

A single tumor contains a heterogeneous population of cancer cells. Some cancer cells express antigens and are susceptible to specific CTLs. However, other cancer cells are antigen-loss variants (ALVs) that escape these CTLs because they express little or no antigen. Here, we show that antigen-specific T cells can eliminate ALVs when the parental population expresses a model gp33 antigen (KAVYNFATM) at a level sufficient to be locally cross-presented by the nonmalignant stromal cells. That is, the ALVs are eliminated as bystanders because the stroma is destroyed. ALVs escape bystander killing when the bone marrow-derived and/or non-bone marrow-derived stroma does not express the appropriate MHC or when the amount of antigen is too low for effective cross-presentation. The rapid destruction of the stroma, including bone marrow-derived as well as sessile components, and of the parental cancer cells, may be essential for the complete rejection of established tumors by preventing variant escape.

Animals↗
PubMed2003

Analysis of hematopoietic microenvironment containing spatial development of stromal cells in nonwoven fabrics.

We previously reported that a 3D coculture system for hematopoietic cells with spatial development of stromal cells in nonwoven fabrics was superior to a conventional 2D coculture system with respect to progenitor expansion and stem cell maintenance. The hematopoietic environments in 2D and 3D coculture systems were compared and it was found there were no differences in the amounts of soluble factors, e.g., mRNA levels of stem cell factor (SCF) and thrombopoietin (TPO), the secretion of SCF, and hematopoietic stimulating activity of culture supernatant. On the other hand, the total amount of insoluble factors such as extracellular proteins around the stromal cells and the mRNA level of laminin alpha5 were apparently higher in the 3D culture.

Journal Article↗
PubMed2006

Immunophenotypic heterogeneity of bone marrow-derived mesenchymal stromal cells from patients with hematologic disorders: correlation with bone marrow microenvironment.

The immunophenotypic analysis of ex vivo-expanded mesenchymal stromal cells (MSC) has so far been confined to single or dual staining analysis in normal subjects. In this study, using a four-color cytofluorimetric protocol, we demonstrated that cultured MSC derived from the bone marrow of patients with hematologic malignancies showed alterations in the expression of CD105, CD90, CD184, and HLA-DR molecules. The decrease in the percentage of CD105+ and CD90+ MSC correlated with an increased bone marrow angiogenesis. This paper provides evidence that multiparametric flow cytometry is essential for the establishment of a standardized protocol to identify various MSCs subsets and aberrant phenotypes.

Adult↗
PubMedDate not supplied

Prostatic stromal microenvironment and experimental diabetes.

The diabetes causes alterations in various organ systems, including the male accessory sex glands. The prostate is very important in the reproductive process and it is a frequent target of malignant changes. The aim of this work was to demonstrate the histochemical and ultrastructural alterations in the prostate of diabetic animals. Two groups of animals were utilized: control and non-obese diabetic mice (NOD). Twelve days after the characterization of diabetic status the ventral prostate was collected, fixed in Karnovsky and paraformaldehyde, processed for histochemistry and TEM associated to stereology. The results showed reduction of the epithelial area and increasing of the stromal area with muscular and collagen hypertrophy in the prostatic gland. It was characterized the development of prostatic intraepithelial neoplasia, inflammatory processes and dilation of the organelles involved in the secretory process. It was concluded that diabetes besides damaging the reproductive process, affects the glandular homeostasis favoring the development of prostatic pathologies.

Animals↗
PubMed1991

[State of stromal microenvironment of the bone marrow during remission of acute lymphoblastic leukemia in children].

It has been established that bone marrow stroma integrally participates in acute lymphoblastic leukemia (ALL) reparation in children. The regularities of changes in its function were revealed over time and during remissions as was the sensitivity to polychemotherapy carried out during ALL remission. Studies into the function of stromal precursors of fibroblasts provide important information for estimation of hemopoiesis in children undergoing ALL remission.

Adolescent↗