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PubMedDate not supplied

Molecular changes in PDEGF and bFGF in malignant melanomas in relation to the stromal microenvironment.

BACKGROUND: Aberrant expression of either growth factors or growth factor-receptors by stromal cells can be an important factor promoting the growth of solid tumours. It may also affect differentiation of malignant cells and support tumour spread. The aim of the present study was to investigate the hypothesis that basic-fibroblast growth factor (bFGF) and platelet-derived growth factor (PDEGF) may be involved in tumour-stromal microenvironment interactions in primary malignant melanomas. MATERIALS AND METHODS: PDEGF and bFGF expression in malignant cells and surrounding stromal elements was assessed using indirect immunohistochemistry. RESULTS: It was confirmed that PDEGF can be involved in the reciprocal interactions between tumour cells and stroma, including aberrant angiogenesis. Interestingly, bFGF was present both in malignant melanoma lesions and benign nevi accompanied by different intracellular localisation of the protein, suggesting its implication in regulation of nevus cell proliferation and maturation. CONCLUSION: The present results suggest that bFGF and PDEGF participate in malignant melanoma progression.

Fibroblast Growth Factor 2↗
PubMed2005

DNA ploidy, cyclin D1, bcl-2 and lymphocytic infiltration of the tumor microenvironment as prognostic factors in laryngeal cancer patients.

The aim of this study was to evaluate correlations between DNA ploidy type, the immunostaining of cyclin D1, bcl-2 and the intensity of lymphocytic infiltration of the tumor microenvironment in relation to the histopathological G differentiation and pTNM classification. Thirty two patients were treated surgically for laryngeal cancer with total or partial laryngectomy in the Department of Otolaryngology Zabrze. The percentage of bcl-2 immunostaining was showed in 53% of the cases and was found to correlate with G differentiation and the patients' age. Cyclin D1 antigen stained positively in 24 cases (75%). Expression of cyclin D1 correlated with cancer stage. Cyclin D1 negative stain was found in T4-stage. DNA ploidy was examined in 19 cases. Aneuploidy was found in 5 cases only, while the rest were diploid. DNA ploidy value correlated with cyclin D1 expression. All paraffin sections were found to contain lymphocytic infiltrations of CD43 and CD45RO phenotype in the tumor front. Some cases showed high intensity of lymphocytic infiltrations of CD45RO phenotype. The intensity of CD43 lymphocytic infiltrations in the tumor front was related to the expression of cyclin D1 and bcl-2.

Adult↗
PubMedDate not supplied

Arising podosomal structures are associated with neoplastic cell morphological phenotype induced by the microenvironment.

Increased numbers of rosettes of podosomes were observed in overgrown rat Rous sarcoma RsK4 cells. A possible role of these structures in nutrient uptake in tumour cell survival was investigated by exposure to acute starvation. A single cell suspension of RsK4 cells in Hanks balanced salt solution was allowed to interact with either clean uncoated or serum-coated for bait coverglasses. Confocal microscopy revealed contrasting 3D cell morphologies that were associated with conspicuous patterns of podosomal structures, which on the coated coverglasses resembled the sealing zones of osteoclasts, while on the uncoated coverglasses they resembled the marginal podosomes of migrating monocyte-derived cells. Thus, the arising podosomal structures, the involvement of which in an uptake of nutrients appeared feasible morphologically, were associated with the emerging 3D cell shapes guided by the microenvironment. Such phenotypic plasticity of neoplastic RsK4 cells in response to microenvironmental challenge suggested that uniqueness in cellular attributes within the neoplastic cell population could be crucial for the malignant potential.

Actins↗
PubMed2006

[Effects of cyclin dependent protein kinase inhibitor olomoucine on the microenvironment of axonal regeneration after spinal cord injury: an experiment with rats].

OBJECTIVE: To investigate the effects of olomoucine, a cyclin dependent protein kinase (CDK) inhibitor, on the microenvironment of axonal regeneration after spinal cord injury (SCI). METHODS: Forty-five SD rats were randomly divided into 3 equal groups: SCI group undergoing SCI by hemisection technique and peritoneal injection of dimethyl sulfoxide (DMSO) solution 30 min after the SCI, SCI + olomoucine (SCI + Olo) group undergoing SCI by hemisection technique and peritoneal injection of olomoucine solution 30 min after the SCI, and sham operation group undergoing sham operation and peritoneal injection of DMSO solution 30 min after the operation. Three days after the operation the injured spinal cord segments of 5 rats from each group were taken out. Western blotting was used to detect the expression of the cell cycle related proteins, cyclin A, cyclin B, cyclin E, and proliferating cell nuclear antigen (PCNA). Immunofluorescence (IF) staining was used to detect the expression of glial fibrillary acidic protein (GFAP), growth associated protein-43 (GAP-43) and chondroitin sulphate proteoglycan (CSPG). Four weeks after the operation specimens of the injured spinal cord segment 15 mm in length were taken out from 5 rats in each group to undergo histological examination. The locomotion function of the hindlimbs was determined by modified Gale combined behavioral scoring (SBS) 1 day and 1, 2, 4, 6, and 8 weeks after the operation. RESULTS: Western blotting 3 days after the operation showed that the expressions of cyclin A, cyclin B, cyclin E, and PCNA were very weak in the sham operation group, were significantly increased in the SCI group, and were significantly down-regulated in the SCI + Olo group compared with those of the SCI group. IF staining showed that the number of astrocytes was small and the expressions of GFAP, CSPG, and GAP-43 were weak in the sham operation group; in the SCI group the astrocytic proliferation and glial scar was obvious, and the expressions of GFAP, CSPG, and GAP-43 were significantly increased compared with those of the sham operation group (all P < 0.05); and the astrocytic proliferation was significantly weaker and no obvious glial scar could be seen, and the expressions of GFAP and CSPG were weaker in the SCI + Olo group in comparison with the SCI group, however, the GAP-43 expression of the sham operation group was significantly increased compared with that of the sham operation group (P < 0.05). The hindlimbs of the SCI + Olo group and sham operation group were paralyzed without significant difference in the CBS values between these 2 groups, however, two weeks after the operation, the locomotion function scores at different time points of the SCI + Olo group were all significantly improved in comparison with that of the SCI group (all P < 0.05). CONCLUSION: Olomoucine promotes the recovery of the locomotion function of the paralyzed hindlimbs, probably through microenvironmental improvement of axonal regeneration by inhibiting the glial scar formation and CSPG secretion as well as upregulating the GAP-43 expression.

Animals↗
PubMed2006

Clinically relevant oral cancer model for serum proteomic eavesdropping on the tumour microenvironment.

BACKGROUND: Serum proteomics has enormous potential in the identification of biomarkers and the development of new therapies for oral cancer. Current efforts are limited by the lack of a control subject. The human-mouse chimeric model offers a solution. OBJECTIVES: To develop and test two orthotopic xenograft mouse models of human oral squamous cell carcinoma for research in serum proteomics. METHODS: Advanced human oral cancer from three patients was implanted orthotopically into the tongues of 19 SCID and 4 RAG2/gamma(c) knockout (KO) mice. Adjacent normal tissue from each patient was also implanted into nine SCID and 4 RAG2/gamma(c) KO mice. The models were compared for tissue take, the presence of metastasis, and histologic invasiveness. Mouse serum was preserved for studies in serum proteomics. RESULTS: Tumour tissue was successfully implanted into SCID and RAG2/gamma(c) mice, and the invasiveness was confirmed pathologically. Three of the control mice demonstrated the persistence of normal tissue more than 1 month after implantation. This is the first time that this has been reported. The larger size of the RAG2/gamma(c) KO mouse facilitated serum collection for serum proteomics. CONCLUSIONS: Both RAG2/gamma(c) KO and SCID mouse are able to reliably engraft human oral cancer. Engraftment of normal oral tissue was less reliable. This is the first in vivo model allowing identification of proteins released from the tumour microenvironment.

Aged↗
PubMed1991

Functional anatomy of the thymic microenvironment.

This paper presents a review of our current understanding of the nature of the thymic microenvironment, after briefly considering the major role of the gland. The epithelial cells and their products are of fundamental importance, and other cells of the macrophage series are implicated in most functional events. The embryological origin of the epithelium is still not clear, although disease conditions would suggest a single origin. Immigration and emigration of thymocytes is considered, and also the passage of antigens into the gland. The events within the thymus are under the control of the CNS acting through the innervation or via hormonal pathways. Both of these areas are considered in detail, especially thymic hormone origins, functions and interactions.

Animals↗
PubMed1991

[Effects of polysaccharide from Thuja occidentale L. on stromal precursor cells of hematopoietic microenvironment in mice].

The effect of high molecular polysaccharide subfraction from Thuja occidentale L. (TPS) on stromal precursor cells of hematopoietic microenvironment under the "steady-state" conditions and after sublethal irradiation was investigated. The stromal precursor cells of different stages of differentiation were detected by the implantation of mouse bone marrow under the renal capsule of syngeneic intact recipients and chimeras. It was shown that TPS did not occur the toxic influence on the stromal precursor cells and provided the defense effect on them under the strong (6 Gy) radiation damages.

Animals↗
PubMed1991

Elimination of volatile organic compounds in breath after exposure to occupational and environmental microenvironments.

Breath measurements offer the potential for a direct and noninvasive evaluation of human exposure to volatile organic compounds (VOCs) in the environments in which people live and work. This research study was conducted to further evaluate and develop the potential of this exposure assessment methodology. Several people were exposed to the atmosphere in six microenvironments for several hours. Air concentrations of VOCs were measured during these exposures and breath samples were collected and analyzed at multiple time points after the exposure to evaluate elimination kinetics for 21 VOCs. A new alveolar breath collection technique was applied. Elimination half-lives were estimated using a mono- and bi-exponential model. The alveolar breath collection and analysis methodology proved to be very useful for collecting many samples in short time intervals and this capability was very important for more accurately describing the initial phase of the decay curves. Breath decay curves were generated from samples collected over a four hour period after exposure for 21 of 24 target VOCs. A biexponential function generally provided a better fit for the decay data than did the monoexponential function, supporting a multi-compartment uptake and elimination model for the human body.

Air Pollutants↗
PubMed1991

Latent deficiency of the hematopoietic microenvironment of aged mice as revealed in W/Wv mice given +/+ cells.

The macrocytic anemia of W/Wv mice can be cured by injection of +/+ bone marrow cells (BMC) from WBB6F1 mice. However, it has been observed that some W/Wv recipients appear to "lose" their cure with time, an effect that does not appear to be related to the age of the BMC donor. The present study was undertaken to determine the effect of recipient age on W/Wv responses to BMC injection. The effect of aging on erythroid parameters was similar in untreated W/Wv mice and +/+ controls. In both genotypes, hematocrit (HCT) and red blood cell count (RBC) decreased, and the modal red blood cell size (peak) increased between 13 and 150 weeks of age. As anticipated, mean HCT and RBC values were lower and peak values higher in W/Wv mice compared to +/+ controls at every age. However, the rate of decrease in HCT and RBC with age was the same for both genotypes, suggesting that the age effect and W gene effect were independent. Peak values increased slightly more with age for W/Wv than for +/+ controls. When female W/Wv mice in three age groups (23.5, 70, and 91.5 weeks old) were injected with 5 x 10(5) BMC from 20-week-old +/+ female donors and HCT, RBC, and peak were determined monthly, improvement was seen in most W/Wv recipients. However, in the older mice this improvement was slower and often was not sustained; 100% of the youngest recipients, 80% of the middle-aged, and only 30% of the older groups were cured after 3 months. Taken together, these data suggest a latent deficiency of the aging hematopoietic microenvironment that is revealed in W/Wv mice by the stress of continuing erythroid demand on the limited number of normal donor BMC.

Aging↗
PubMed1991

Thymic microenvironment induces HIV expression. Physiologic secretion of IL-6 by thymic epithelial cells up-regulates virus expression in chronically infected cells.

The hallmark of infection with HIV-1 is progressive depletion and qualitative dysfunction of the CD4+ Th cell population in infected individuals. Clinical trials of antiretroviral agents have shown that, despite suppression of virus replication, regeneration of the T cell pool does not occur. One proposed explanation for the defective regenerative capacity of the CD4+ T cell pool is infection of early T lymphocyte progenitors or stem cells. An additional explanation could be failure of cells of the intrathymic microenvironment (thymic epithelial (TE) cells) to carry out critical nurturing functions for developing thymocytes, i.e., secretion of thymocyte-trophic cytokines and expression of adhesion molecules. This study examines the effect of HIV on cultured TE cells and determines the role of TE cells in the regulation of viral expression in chronically HIV-infected cells. We found no evidence of infection of TE cells after exposure to HIV-1. However, normal human serum induced secretion of IL-6 by TE cells; induction of TE IL-6 was partially blocked by anti-IFN-gamma antibodies. Moreover, supernatants from TE cells maintained in normal human serum up-regulated HIV replication in chronically HIV-1-infected cells. Because intrathymic T cell precursors can be infected with HIV and T cell precursors come into close contact with TE cells in the thymus, IL-6 secreted by TE cells during normal intrathymic development may induce HIV expression in infected thymocytes in vivo and promote the intrathymic spread of HIV.

Cell Communication↗
PubMed1991

[Ultrastructural organization of the hematopoietic microenvironment of human bone marrow].

The results have been presented of electron-microscopic and ultracytochemical investigations of sinusoidal vessels, fat, reticular and endosteal cells of the bone marrow from the iliac bone fragments of 30 normal subjects. Close morphological and functional relationships have been established between the structures of the hemopoietic microenvironment and hemopoietic cells, and the role of certain stromal elements in the maintenance of the hemopoietic function has been specified.

Bone Marrow Cells↗
PubMed1990

[Spreading depression--cortical reactions: disorders of the extracellular microenvironment].

Changes of brain cell microenvironment in the cerebral cortex of the rat were studied during spreading depression (SD) elicited by KCl application or local cooling. The question was whether the behavior of extracellular ion concentrations, especially of K+, could give some information about the triggering mechanisms of SD at the site where the phenomenon originates in the tissue. SDs elicited by KCl and recorded far from their original sites were associated with disturbances of extracellular ion concentrations and of tissue pO2 and pCO2 showing characteristic time sequences. Under these conditions none of the parameters studied changed before SD development. When an SD was elicited by local cooling extracellular K+ concentration ([K+]0) increased steeply in the mostly cooled cortical layers prior to SD initiation and formed a plateau of about 10 mmol/l resembling the ceiling level for K+ associated with ictal seizure activity. The front of the SD wave moved down slowly to the white matter. Thereby the rectangular rise in [K+]0 prior to SD progressively flattened and finally disappeared. The results suggest that SD evoked by local cooling originates from a primary increase of [K+]0 to the K+ ceiling level and by a secondary breakdown of the mechanisms being responsible for this type of K(+)-regulation. The mechanisms mentioned may be responsible for all kinds of SD-triggering.

Animals↗
PubMed1990

Microenvironment of the peripheral nervous system under normal and pathological conditions.

The peripheral nervous system (PNS) is composed of neurons and their processes which are located in a special fluid microenvironment. As is well known, complex biological functions such as those going on in peripheral nerves are best carried out when there is homeostasis, i.e., in a constant internal milieu. This paper is concerned with the maintenance of the homeostasis in the PNS under normal and pathological conditions. Diffusion barriers located in the intrinsic vessels of the PNS and the perineurium have the capacity to regulate the environment around the nerve fibers and to keep it away from the blood and the extracellular fluid outside the PNS. Endoneurial vascular permeability has similarities to that in the central nervous system, but compared with the blood-brain barrier the blood-nerve barrier is less efficient. This implies that toxic and infectious agents as well as some drugs have easier access to the parenchyma in nerves than to the brain parenchyma. However, ganglionic vessels lack an efficient vascular barrier to many substances which is important in intoxications caused by, e.g., doxorubicin, lead, mercury, and cadmium. It has also a significance in herpes zoster infection and presumably in Guillain-Barré syndrome. The diffusion barriers may themselves be influenced by pathologic processes and can then respond with an increased permeability. This may lead to the formation of edema in the PNS, i.e., one of the cardinal features of many diseases in nerves of traumatic, toxic, and inflammatory nature. Such a response had negative as well as positive implications. Severe edema may disturb the normal microcirculation in the endoneurial vessels and stimulate collagen production and fibrosis. However, the presence of a protein-rich endoneurial edema may well be important in repair processes such as reduplication of Schwann cells and growth of axons.

Animals↗
PubMed1990

[Preovulatory human oocyte and its hormonal microenvironment in stimulated cycles].

The hormonal microenvironment of 213 follicles in 44 stimulated cycles was analysed. Mature and intermediate oocytes were found to be associated with larger follicles which contained significantly higher levels of E2, P, FSH and LH, while smaller follicles containing significantly higher T level usually gave rise to immature oocytes. The fertilization rate was higher in mature and intermediate oocytes than in immature oocytes. In this study there was no significant difference in the cleavage rate of the fertilized eggs in relation to the E2, P, T, FSH and LH concentrations in follicular fluid as well as to the contents of these hormones per follicle.

Adult↗
PubMed1990

[Role of stromal microenvironment in the regulation of bone marrow hemopoiesis after curantyl administration].

Role of the stromal microenvironment in regulation of bone marrow hemopoiesis at the administration of the thrombocyte disaggregant curantyl was studied by the method of heterotopic transplantation of the mice bone marrow. It is shown that the action of curantyl on hemopoiesis is realised through the stem stromal cells of the bone marrow. It is noted that the inhibitory action of the preparation on proliferation of osteogenic precursor-cells is followed by activation of bone resorption processes in regenerating ectopic hemopoietic organ. Under the action of curantyl at low bone marrow cellularity in the focus of heterotopic hemopoiesis and femur an increase of mitotic activity in hemopoietic elements is noted. It is revealed that a phenomenon of ineffective megakaryocytopoiesis with intramedullary destruction of megakaryocytes leads to the local excretion of the thrombocyte released growth factor (TRGF) which has a compensatory character.

Animals↗
PubMed1990

Maturation-dependent adhesion of human B cell precursors to the bone marrow microenvironment.

Murine B cell precursors can be induced to proliferate in culture if allowed to bind to bone marrow derived adherent cells prepared under specific conditions. We studied the binding of human B cell precursor subpopulations to various in vitro microenvironments to determine which conditions may potentially be suitable models for human B precursor differentiation. Using the markers CD10, CD34, and CD20, B lineage populations of increasing maturation were quantitated: CD10+/CD34+, CD10+/CD20-, CD10+/CD20+, and CD10-/CD20+ cells in marrow, and CD10-/CD20+ mature B cells in peripheral blood. The adhesion of subpopulations of blood and marrow-derived light density cells to adherent cell layers or matrix was studied following a 2-h incubation in 24-well plates. The absolute number of bound B lineage cells was determined by cell counts and flow cytometry analysis. The adherence of B lineage cells to passaged human marrow fibroblasts (BM-FB) was highest in the most immature CD10+/CD34+ cells (34.3 +/- 4.2%), decreasing steadily with each stage of maturation to the peripheral blood B cells (11.2 +/- 2.4%). Increased adhesion of CD10+ B cell precursors relative to CD10-/CD20+ marrow B cells was confirmed by adhesion studies using sorted cells. The two most immature B lineage cells (CD10+CD34+ and CD10+/CD20-) showed more adherence to BM-FB than any other cell type tested, except for monocytes. Only B lineage precursor cells, erythroid precursors and CD10-/CD34+ cells showed significantly greater binding to BM-FB than to plastic. B lineage precursors bound equally well to primary and passaged human marrow fibroblasts, but bound significantly less well to passaged human foreskin fibroblasts, primary human marrow stroma, extracellular matrix of marrow fibroblasts, or fibronectin. These results suggest that specific binding to marrow fibroblasts is part of the differentiation program of early B lineage precursors. This binding activity gradually and predictably decreases during B lineage differentiation, in contrast to expression of other binding receptors, such as LFA-1 and CD44, which increase during B lineage maturation.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1986

Chemosensitivity testing in V79 spheroids: drug delivery and cellular microenvironment.

Chinese hamster V79 multicell spheroids growing in tissue culture exhibit many of the same properties as solid tumors outgrowing their blood supply, including the spontaneous development of both noncycling and hypoxic cell populations expected to be resistant to many chemotherapeutic agents. Cell-sorting techniques were used to select cells as a function of their position (depth) within the spheroid to test this prediction. "Sensitivity profiles" of cells from various regions within spheroids after treatment with doxorubicin, bleomycin, 5-fluorouracil, carmustine, cisplatin, chlorambucil, and mitomycin are presented. Additionally, exposure of preseparated cells was used to distinguish inherent sensitivity from environmental or locational factors. For these drugs, penetration was a problem only for doxorubicin; in contrast, the microenvironment in the intact spheroid had a much greater influence on cell sensitivity.

Animals↗
PubMed1989

The hematopoietic microenvironment in the elderly: defects in IL-1-induced CSF expression in vitro.

The expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) genes by stromal cells of the hematopoietic microenvironment is regulated, in vitro, by interleukin 1 alpha (IL-1 alpha) and IL-1 beta. We reasoned that malfunction of this inductive mechanism in vivo might contribute to the intolerance of the aged to myelosuppressive therapy. We found that bone marrow fibroblasts from healthy elderly (ages 65-75 years) volunteers were less sensitive to the inductive effects of recombinant IL-1 beta than were marrow fibroblasts from younger volunteers, and we proposed that an age-related decline in sensitivity of marrow stroma to IL-1 may impair the ability of the elderly to increase production of hematopoietic growth factors under conditions of physiologic stress.

Adult↗