Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “microenvironment”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,549 records · Page 86Linked to original sources
PubMed2004

Peritoneal inflammation - A microenvironment for Epithelial Ovarian Cancer (EOC).

Epithelial ovarian cancer (EOC) is a significant cause of cancer related morbidity and mortality in women. Preferential involvement of peritoneal structures contributes to the overall poor outcome in EOC patients. Advances in biotechnology, such as cDNA microarray, are a product of the Human Genome Project and are beginning to provide fresh opportunities to understand the biology of EOC. In particular, it is now possible to examine in depth, at the molecular level, the complex relationship between the tumor itself and its surrounding microenvironment.This review focuses on the anatomy, physiology, and current immunobiologic research of peritoneal structures, and addresses certain potentially useful animal models. Changes in both the inflammatory and non-inflammatory cell compartments, as well as alterations to the extracellular matrix, appear to be signal events that contribute to the remodeling effects of the peritoneal stroma and surface epithelial cells on tumor growth and spread. These alterations may involve a number of proteins, including cytokines, chemokines, growth factors, either membrane or non-membrane bound, and integrins. Interactions between these molecules and molecular structures within the extracellular matrix, such as collagens and the proteoglycans, may contribute to a peritoneal mesothelial surface and stromal environment that is conducive to tumor cell proliferation and invasion. These alterations need to be examined and defined as possible prosnosticators and as therapeutic or diagnostic targets.

Journal Article↗
PubMed2003

Host microenvironment in breast cancer development: inflammatory and immune cells in tumour angiogenesis and arteriogenesis.

Breast cancer progression is associated with and dependent upon robust neovascularization. It is becoming clear that tumour-associated 'normal' cells, such as immune/inflammatory cells, endothelial cells and stromal cells, conspire with cancer cells in promoting this process. In particular, infiltrating immune/inflammatory cells secrete a diverse repertoire of growth factors and proteases that enable them to enhance tumour growth by stimulating angiogenesis and, as we suggest here, by promoting 'tumour arteriogenesis' - enlargement of feeding vessels supplying the expanding tumour capillary bed. Macrophages and their chemoattractants (e.g. macrophage chemoattractant protein-1) are critical for the arteriogenic process in ischaemia, and probably also in breast neoplasia. A better understanding of these various cellular and molecular constituents of breast cancer neovascularization may be useful in designing more effective therapies.

Animals↗
PubMed2003

Host microenvironment in breast cancer development: epithelial-mesenchymal transition in breast cancer development.

The epithelial-mesenchymal transition (EMT) is a developmental mechanism of crucial importance in establishing the body plan in many multicellular organisms. Several transduction pathways controlling the various steps of the morphological transition have been identified by molecular analyses of this process in cell lines and in vivo. The newly formed mesenchymal cells can exhibit locomotory and invasive phenotypes, suggesting that EMTs contribute to the progression of carcinoma. Diverse evidence indicates that EMT subprograms are involved in the appearance of different breast carcinoma types. Several normal and malignant breast cell lines are currently being analyzed to define key steps in EMT and to identify candidate genes. DNA profiling technology is also being applied to uncover pathways that lead to a metastatic phenotype.

Animals↗
PubMed2003

Host microenvironment in breast cancer development: extracellular matrix-stromal cell contribution to neoplastic phenotype of epithelial cells in the breast.

Epithelial-mesenchymal interactions play an important role both in normal mammary gland development and during neoplastic transformation. Perturbations in the production, deposition and degradation of the extracellular matrix occurring during neoplastic transformation and progression have been implicated to arise from alterations in the stromal response. These changes in the stroma exhibit a dominant regulatory role, via microenvironmental epigenetic effectors, to contribute to the development of the tumorigenic epithelial phenotype. The role of stromally derived microenvironmental epigenetic effectors in modulating epithelial growth, hormonal response, morphogenesis and epithelial plasticity is discussed.

Animals↗
PubMed2003

Host microenvironment in breast cancer development: epithelial-cell-stromal-cell interactions and steroid hormone action in normal and cancerous mammary gland.

Mammary epithelial cells comprise the functional component of the normal gland and are the major target for carcinogenesis in mammary cancer. However, the stromal compartment of the normal gland and of tumors plays an important role in directing proliferative and functional changes in the epithelium. In vivo and in vitro studies of the murine mammary gland have provided insights into novel stroma-dependent mechanisms by which estrogen and progesterone action in the epithelium can be modulated by hepatocyte growth factor (HGF) and the extracellular matrix proteins, collagen type I, fibronectin and laminin. In vitro and in vivo studies of estrogen receptor positive, estrogen-responsive human breast cancer cells have also demonstrated that estrogen responsiveness of tumor cells can also be modulated by extracellular matrix proteins, collagen type I and laminin.

Animals↗
PubMed2004

Multistep tumorigenesis and the microenvironment.

Early-stage cancers have long been considered to be less aggressive than late-stage cancers because it is assumed that they have accumulated fewer of the mutations that are required for full metastatic potential. For breast cancer, recent gene expression profiling data have challenged this paradigm by identifying early-stage cancers with similar gene expression profiles to fully metastatic cancers. In this review, multistep carcinogenesis is reconsidered in light of these new data. The concept that the tumor stroma plays a key role in determining whether a metastatic tumor cell will remain dormant or become invasive is discussed. Recent studies demonstrating the feasibility of targeting tumor stroma for cancer prevention and treatment are presented.

Animals↗
PubMed2004

The mast cell: an antenna of the microenvironment that directs the immune response.

Mast cells (MCs) have long been considered as critical effector cells during immunoglobulin (Ig)E-mediated allergic disease and immune response to parasites. Recent studies, however, suggest that this understanding of MC function is incomplete and does not consider the complex roles that MCs play in adaptive and innate immunity. The added function gives an innovative vision of regulation of immune responses and the development of autoimmune diseases. It had been assumed that the aggregation of Fc epsilon receptor I with IgE and specific antigen is the main stimulus able to induce the MC activation, degranulation, release, and generation of mediators of the allergic reaction. However, MCs exhibit an array of molecules involved in cell-cell and cell-extracellular matrix adhesion, mediating delivery of costimulatory signals that empower those cells with an ability to react to multiple nonspecific and specific stimuli. Their tissue distribution and their capability to release many cytokines after stimulation indicate MCs as potential regulatory linkers between innate and acquired immunity. In this review, we will summarize some findings on the roles of MCs in innate and acquired immunity, on the molecular mechanism and signaling pathways, and on selective signals that induce discrete MC response and its ability to polarize adaptive-immune response.

Animals↗
PubMed2005

The androgen microenvironment of the human testis and hormonal control of spermatogenesis.

It is well established for both rat and man that the total testosterone concentration within the testis is far higher than that in serum. We know for the rat that intratesticular testosterone can be reduced by 50-60% without an adverse effect on spermatogenesis but that the required intratesticular testosterone concentration is still 10-fold greater than serum testosterone concentration. This kind of information, if available for the human, could prove invaluable for understanding and treating select men with infertility and in the development of male hormonal contraceptives. Unfortunately, we know little about the androgen content of intratesticular fluid within the human testis and nothing about the relationship between intratesticular androgens and human spermatogenesis. Using a newly developed minimally invasive technique for repetitive testicular sampling, our recent studies of the human have demonstrated that, as in the rat, there is a gradient between the concentration of testosterone in serum and within the testis; intratesticular testosterone levels were found to be 100-fold higher than serum testosterone levels in normal men. Using liquid chromatography tandem mass spectroscopy, we have shown that intratesticular 5alpha-dihydrotestosterone (DHT) levels are only 2% that of testosterone and, thus, despite greater affinity for the androgen receptor, intratesticular DHT is not significant in normal men. In order to assess how much of the testosterone within the human testis is bioactive, we adapted a highly sensitive recombinant protein mammalian cell-based bioassay to measure androgen bioactivity. The androgen bioactivity in the normal human testis is roughly two-thirds that of the total testosterone measurable by radioimmunoassay, despite the fact that the concentrations of the major androgen-binding proteins (sex hormone-binding globulin- and androgen-binding protein) are insufficient to account for this difference. This finding suggests that androgens may bind to other, as-yet-unknown molecules in the human testis. How, or if, this relates to spermatogenesis in the rat, or to man-to-man differences in the response to hormonal contraceptives, is not clear. We do not yet know how much testosterone is required within the human testis to either maintain or restore quantitatively normal spermatogenesis because, as yet, experimental studies comparable to those performed in the rat have not been feasible for the human.

Androgens↗
PubMed2005

Neoadjuvant immunotherapy of oral squamous cell carcinoma modulates intratumoral CD4/CD8 ratio and tumor microenvironment: a multicenter phase II clinical trial.

PURPOSE: To investigate the clinicopathologic effects of local neoadjuvant Leukocyte Interleukin Injection (LI) regimen in oral squamous cell carcinoma (OSCC) patients. Treatment regimen included LI 800 IU/d as interleukin-2 (IL-2), administered half peritumorally and half perilymphatically five times per week for 3 weeks; low-dose cyclophosphamide; indomethacin; zinc; and multivitamins. PATIENTS AND METHODS: Thirty-nine patients diagnosed with T2-3N0-2M0 OSCC participated in the pathology portion of this phase II multicenter study (19 LI-treated patients and 20 historical controls). Clinical responses were determined by imaging. Paraffin-embedded tumor samples were obtained at surgery for all patients. Surgery for the LI-treated group was performed between days 14 and 54 after the end of treatment. Histologic evaluation, pathologic staging, necrosis, and American Joint Committee on Cancer grading were performed from hematoxylin and eosin sections. Immunohistochemistry and morphometry determined cellular infiltrate. RESULTS: Two pathologically complete, two major (> 50%), and four minor responses (> 30% but < 50%) resulted from LI treatment (overall response rate, 42%). Histopathology showed that the intratumoral CD4+:CD8+ ratio was low (< 1) in patients not treated with LI (controls). An increase in tumor-infiltrating CD4+ and a decrease of CD8+ T cells was observed in LI-treated patients, leading to a significantly (P < .05) higher intratumoral CD4+:CD8+ ratio (> 2.5). This was paralleled by dendritic cell transition from tumor surface toward stromal interface (P < .05), with macrophage decrease and neutrophil accumulation, multifocal microscopic necrosis, and significant (P < .05) increase in tumor stroma of LI-treated patients compared with controls. CONCLUSION: LI-treated OSCC patients were characterized by a markedly altered composition of tumor-infiltrating mononuclear cells, increased CD4+:CD8+ ratio, and increased tumor stroma to epithelial ratio, all of which were distinct from controls.

Adult↗
PubMed1984

On the androgen microenvironment of maturing spermatozoa.

Adult anesthetized male rats were submitted to in vivo micropuncture of the seminiferous and epididymal tubules and reproductive tract vasculature to obtain fluids for analysis of testosterone, 5 alpha-dihydrotestosterone, and androgen-binding protein (ABP). Androgen and ABP concentrations were determined by RIA. The highest concentrations of testosterone (73.14 +/- 5.12 ng/ml) were in testicular interstitial fluid. A significant downhill concentration gradient exists between testosterone concentrations in testicular interstitial fluid and seminiferous tubule fluid (50.24 +/- 2.26 ng/ml); another significant decrease occurs between seminiferous tubule fluid and rete testis fluid (17.85 +/- 2.11 ng/ml). 5 alpha-Dihydrotestosterone concentrations were highest in intraluminal caput epididymidal fluids (58.73 +/- 6.48 ng/ml) as were ABP concentrations (33.30 +/- 2.40 mu leq/microliter). Intraluminal sperm concentrations were also determined, and from these data, fluid reabsorption by the efferent ducts and epididymal tubules were calculated. Eighty-nine percent of the fluid leaving the testis is reabsorbed between the rete testis and caput epididymidis, and 96% is reabsorbed between rete and cauda. It was calculated that large losses of androgen and ABP also occur from the lumen of the excurrent duct system. These losses may be due to metabolism, diffusion from the lumen, or uptake by cells.

Androgen-Binding Protein↗
PubMed1996

Cytokine production in the bone marrow microenvironment: failure to demonstrate estrogen regulation in early postmenopausal women.

Recent studies in rodents and in human in vitro systems suggest that the action of estrogen on bone is modulated by various bone-resorbing cytokines produced by osteoblasts, bone marrow cells, or both, but results among studies have been conflicting. Thus, we studied 20 untreated women (controls) and 20 women who had received estrogen replacement therapy since the time of menopause; both groups were 5 +/- 1 yr (mean +/- SE) postmenopausal. From bone marrow aspirates, we obtained marrow plasma to evaluate the production of cytokines by marrow and trabecular bone cells in vivo and marrow mononuclear cells to assess in vitro the constitutive and lipopolysaccharide-stimulated production of cytokines and also to test the in vitro effects of 17 beta-estradiol (10(-8) mol/L). Interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, IL-1 receptor antagonist, and IL-6-soluble receptor were measured by specific enzyme-linked immunosorbent assay. No statistically significant difference between the two groups in the level of any of these cytokines was detected in the bone marrow plasma or the conditioned medium in vitro. Furthermore, in vitro treatment with 17 beta-estradiol did not affect basal or lipopolysaccharide-stimulated cytokine production. Thus, our data suggest that for normal post-menopausal women, mediation of the effects of estrogen by a single cytokine is unlikely. Either multiple cytokines are involved and small changes in these are difficult to detect in clinical investigative studies, or other mechanisms are operative.

Antigens, CD↗
PubMed2001

Cells in regenerating deer antler cartilage provide a microenvironment that supports osteoclast differentiation.

Deer antlers are a rare example of mammalian epimorphic regeneration. Each year, the antlers re-grow by a modified endochondral ossification process that involves extensive remodelling of cartilage by osteoclasts. This study identified regenerating antler cartilage as a site of osteoclastogenesis in vivo. An in vitro model was then developed to study antler osteoclast differentiation. Cultured as a high-density micromass, cells from non-mineralised cartilage supported the differentiation of large numbers of osteoclast-like multinucleated cells (MNCs) in the absence of factors normally required for osteoclastogenesis. After 48 h of culture, tartrate-resistant acid phosphatase (TRAP)-positive mononuclear cells (osteoclast precursors) were visible, and by day 14 a large number of TRAP-positive MNCs had formed (783+/-200 per well, mean +/- s.e.m., N=4). Reverse transcriptase/polymerase chain reaction (RT-PCR) showed that receptor activator of NF &kgr; B ligand (RANKL) and macrophage colony stimulating factor (M-CSF) mRNAs were expressed in micromass cultures. Antler MNCs have the phenotype of osteoclasts from mammalian bone; they expressed TRAP, vitronectin and calcitonin receptors and, when cultured on dentine, formed F-actin rings and large resorption pits. When cultured on glass, antler MNCs appeared to digest the matrix of the micromass and endocytose type I collagen. Matrix metalloproteinase-9 (MMP-9) may play a role in the resorption of this non-mineralised matrix since it is highly expressed in 100 % of MNCs. In contrast, cathepsin K, another enzyme expressed in osteoclasts from bone, is only highly expressed in resorbing MNCs cultured on dentine. This study identifies the deer antler as a valuable model that can be used to study the differentiation and function of osteoclasts in adult regenerating mineralised tissues.

Acid Phosphatase↗
PubMed1979

Thermoacclimatory changes in the ionic microenvironment of haemoglobin in the stenothermal rainbow trout (Salmo gairdneri) and eurythermal carp (Cyprinus carpio).

1. Haematological characteristics (erythrocyte number, haematocrit, haemoglobin, mean erythrocyte volume and haemoglobin content) and plasma and packed red blood cell water and electrolyte (Na+, K+, Ca2+, Mg2+, Cl-) levels were determined in summer and winter populations of rainbow trout acclimated to 2, 10 and 18 degrees C, and for carp held at 2, 16 and 30 degrees C. Erythrocyte electrolyte concentrations and ion:haemoglobin ratios were calculated from these data. 2. Modest increases in red cell abundance and reductions in mean erythrocytic volume were the most obvious haematological changes accompanying acclimation to higher temperatures. Haemoglobin levels in carp also tended to increase with temperature. 3. In winter trout plasma sodium and potassium were elevated following acclimation to increased temperature. No significant cges in plasma composition were observed in summer fish. Carp held at higher temperatures were characterized by increases in plasma chloride and calcium and reductions in sodium and magnesium levels. 4. Red cell potassium and magnesium and K+:Hb and Mg2+:Hb ratios tended to be higher in winter than in summer trout, with the converse being true of chloride and calcium and Cl-:Hb and Ca2+:Hb. Only potassium and K+:Hb were significantly altered following acclimation; rising at higher temperatures. In carp, potassium and K+:Hb were relatively thermostable, but sodium and chloride and Na+:Hb and Cl-:Hb increased with temperature while magnesium and Mg2+:Hb decreased. Changes in the ionic composition of carp red cells support the suggestion that cellular pH is reduced in the warm-acclimated animal. 5. These variations may be of adaptive value. Increases in chloride and hydrogen ion commonly reduce haemoglobin=oxygen affinity, and should facilitate oxygen unloading at the tissue level. Reductions in cellular magnesium, by maximizing organophosphate modulator levels, should produce much the same effect. 6. In both species reductions in mean erythrocytic volume took place at higher temperatures despite increases in cellular ion content which exceeded those of plasma. It is probable that reductions in cellular volume, which should favour branchial oxygen loading, were achieved by export of some as yet unidentified solute or solutes.

Acclimatization↗
PubMed2006

Effects of neopterin on the hematopoietic microenvironment of senescence-accelerated mice (SAM).

The pteridine neopterin (NP) is produced by monocytes and is known to be a useful marker of immunological activation, although, it remains elusive whether neopterin itself exhibits biological functions. Recently, we found that NP stimulates hematopoietic cell proliferation and differentiation by activating bone marrow stromal cell function. In order to elucidate the biological effect of NP on stromal cells, its effects on hematopoiesis was determined in the mouse model of age-related stromal impairment, senescence-accelerated mice (SAMs). An intraperitoneal administration of NP increased the number of peripheral leukocytes and CFU-GM in the bone marrow and spleen of young SAMs, however, no increase of CFU-GM in old SAMs (stromal impairment) was observed when compared with young SAMs. NP also increased the CFU-GM colony formation of bone marrow and spleen cells from young SAMs in a soft agar culture system, but it did not enhance CFU-GM colony formation of cells from old SAMs cultured in this system. Treatment with NP induced the production of hematopoietic stimulating factors, including IL-6 and GM-CSF, by bone marrow stromal cells from young SAMs but stromal cells from old SAMs did not respond to NP stimulation. Further studies will be required to clarify the mechanism by which NP stimulates the production of hematopoietic growth factors from stromal cells, the results of this study indicate that NP is a potent hematopoietic regulatory factor by activating stromal cell function(s).

Aging↗