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PubMed2002

Effects of mutations in the adenoviral E1B 55-kilodalton protein coding sequence on viral late mRNA metabolism.

The human subgroup C adenoviral E1B 55-kDa protein cooperates with the viral E4 Orf6 protein to induce selective export of viral, late mRNAs from the nucleus to the cytoplasm. Previous studies have suggested that such preferential transport of viral mRNA and the concomitant inhibition of export of cellular mRNAs are the result of viral colonization of specialized microenvironments within the nucleus. However, neither the molecular basis of this phenomenon nor the mechanism by which the E1B 55-kDa protein acts has been elucidated. We therefore examined viral late mRNA metabolism in HeLa cells infected with a series of mutant viruses that carry insertions at various positions in the E1B protein coding sequence (P. R. Yew, C. C. Kao, and A. J. Berk, Virology 179:795-805, 1990). All the mutations examined impaired cytoplasmic accumulation of viral L2 mRNAs and reduced L2 mRNA export efficiency. However, in most cases these defects could be ascribed to reduced E1B 55-kDa protein concentration or the unexpected failure of the altered E1B proteins to enter the nucleus efficiently. The latter property, the pleiotropic defects associated with all the mutations that impaired nuclear entry of the E1B protein, and consideration of its primary sequence suggest that these insertions result in misfolding of the protein. Insertion of four amino acids at residue 143 also inhibited viral mRNA export but resulted in increased rather than decreased accumulation of the E1B 55-kDa protein in the nucleus. This mutation specifically impaired the previously described association of the E1B protein with intranuclear structures that correspond to sites of adenoviral DNA replication and transcription (D. Ornelles and T. Shenk, J. Virol. 65:424-439, 1991) and the colocalization of the E1B and E4 Orf6 proteins. As this insertion has been shown to inhibit the interaction of the E1B with the E4 Orf6 protein in infected cell extracts (S. Rubenwolf, H. Schütt, M. Nevels, H. Wolf, and T. Dobner, J. Virol. 71:1115-1123, 1997), these phenotypes provide direct support for the hypothesis that selective viral mRNA export is determined by the functional organization of the infected cell nucleus.

Adenovirus E1B Proteins↗

PubMed1999

Increased expression of activation markers and adhesion molecules on lung T-cells compared with blood in the normal rat.

Lymphocytes play an important role in many lung diseases and are routinely accessible by bronchoalveolar lavage (BAL). Lymphocytes from the BAL (BAL pool) have a different subset composition to those from peripheral blood, consisting mainly of activated T-cells. The aim of this study was to examine whether preferential migration of activated T-cells to the bronchoalveolar space or factors of the specific microenvironment mediate this phenomenon. The expression of adhesion molecules and cellular activation markers (intercellular adhesion molecule-1, leukocyte function-associated antigen-1, CD2, CD44, interleukin-2 receptor and L-selectin) was studied on T- and B-cells not only in the BAL and peripheral blood (blood pool), but also in the compartments in between, such as the lung vascular perfusate (marginal pool) and the lung interstitium (interstitial pool), with the experiments being performed simultaneously in the same animals. Low levels of adhesion molecule expression were observed on T-cells in the blood and marginal pool, medium levels in the lung interstitium and the highest levels in the BAL. "Memory" (CD45R(low)) and "naive" (CD45R(high)) T-cells in the lung compartments showed a higher expression of adhesion molecules compared with blood. However, the predominating CD45R(low) T-cells showed a significantly higher expression than the CD45R(high) cells, indicating that CD4+ CD45R(high) T-cells had changed their phenotype to CD45R(low). In conclusion, a high level of expression of leukocyte function associated antigen-1 and intracellular adhesion molecule-1 on the bronchoalveolar lavage and interstitial T-cells is more likely to be the result of local, lung-specific induction than a prerequisite for migration into the bronchoalveolar space.

Animals↗

PubMed2026

Research progress on multi-mechanism analysis and protection strategies of ovarian aging and fertility decline.

Age-related fertility decline is an increasingly important challenge in reproductive medicine, driven largely by progressive ovarian aging. The aging ovary undergoes functional deterioration characterized by reduced ovarian reserve and declining oocyte quality, ultimately limiting female reproductive lifespan. Although multiple molecular and cellular processes associated with ovarian aging have been identified, these mechanisms are often discussed independently, limiting an integrated understanding of how they interact within the ovary. In this review, we propose an ovary-centered, multi-mechanistic framework to organize current evidence on ovarian aging and fertility decline. We discuss how genomic instability, telomere attrition, mitochondrial dysfunction, oxidative stress, chronic cellular stress responses, and alterations in ovarian signaling and microenvironmental homeostasis collectively contribute to follicle depletion and impaired oocyte competence. Particular emphasis is placed on signaling pathways involved in follicle activation and stress adaptation, including PI3K/AKT/mTOR, FOXO3, Hippo, and AMPK-Sirtuin networks, while acknowledging that many mechanistic relationships remain incompletely defined in physiological ovarian aging. Building on this integrative perspective, we further evaluate mechanism-oriented intervention strategies, including mitigation of cellular stress, metabolic and signaling modulation, optimization of the ovarian microenvironment, established fertility preservation technologies, and emerging exploratory approaches. By integrating current mechanistic and translational evidence, this review provides a conceptual framework for understanding ovarian aging and highlights future directions for evidence-based fertility preservation and reproductive health management in the context of aging.

Humans↗

PubMed1996

The proliferative responses of porcine thyroid follicular cells to epidermal growth factor and thyrotrophin reflect the autocrine production of transforming growth factor-beta 1.

The present study has investigated an involvement of autocrine transforming growth factor-beta 1 (TGF-beta 1) in regulating the proliferative response of porcine thyroid follicular cells (TFCs) to epidermal growth factor (EGF) and TSH. Primary monolayer TFC cultures exposed to EGF over the range 0-0.4 nmol/l showed a dose-dependent increase in [methyl-3H]thymidine incorporation, whereas higher EGF doses were associated with a reduction in the level of [methyl-3H]thymidine incorporation. TGF-beta immunoneutralisation had little effect on the stimulatory action of low EGF doses, but led to an increase in [methyl-3H]thymidine incorporation at higher EGF levels. In TFC cultures exposed to TSH, the level of [methyl-3H]thymidine incorporation attained at a dose of 1 U TSH/1 was enhanced in the presence of TGF-beta 1 antiserum, although the similar stimulatory effect of 8-bromo cAMP was unaffected. Treatment of TFCs with phorbol 12-myristate 13-acetate (8 nmol/l) to activate protein kinase C (PKC) led to an enhanced incorporation of [methyl-3H]thymidine which was increased further after neutralisation of endogenous TGF-beta 1. While confirming, therefore, a role for autocrine TGF-beta 1 in maintaining control of TFC DNA synthesis in vitro, these findings provide evidence that an increase in the availability of autocrine TGF-beta 1 effected by EGF and TSH may play an instrumental role in limiting the cellular hyperplasia induced by these factors within the thyroid follicular microenvironment. Moreover, the present data also suggest that the availability of active autocrine TGF-beta 1 to TFCs under such conditions may be dependent upon a PKC-mediated mechanism.

Animals↗

PubMedDate not supplied

The role of apoptosis in the pathophysiology of chronic neutropenias associated with bone marrow failure.

Chronic neutropenia syndromes associated with bone marrow (BM) failure comprise distinct congenital and acquired hematologic disorders with varying degree of neutropenia due to decreased or ineffective BM neutrophil production. Recent evidence suggests that defective granulocytopoiesis in these neutropenia states is a consequence of accelerated apoptotic cell death of BM myeloid progenitor cells and/or their differentiated progeny. Inherited or spontaneously appearing mutations in the ELA2 gene encoding for neutrophil elastase have been implicated in the accelerated apoptotic process of the BM myeloid cells in patients with cyclic and severe congenital neutropenia. A disturbed balance between pro-apoptotic and anti-apoptotic intracellular or membrane molecules such as downregulation of the bcl-2 family members or upregulation of the death receptor Fas, have been implicated in neutropenia associated with myelokathexis, Shwachman-Diamond syndrome and acquired chronic idiopathic neutropenia of adult. In this review we summarize the available evidence suggesting that abnormally increased apoptosis and impaired proliferative and differentiating properties of neutrophil progenitor and precursor cells represent a common pathogenetic mechanism for impaired granulocytopoiesis in both acquired idiopathic and congenital neutropenia states. The underlying distinct cellular and molecular abnormalities and the role of the BM microenvironment are extensively analysed.

Apoptosis↗

PubMed1991

Follicular dendritic cells contain a unique gene repertoire demonstrated by single-cell polymerase chain reaction.

Follicular dendritic cells (FDCs) form a dense network between B cells within the germinal center and are thought to be an important component of this B-cell microenvironment. Previous immunophenotypic studies have been inconclusive in determining the cellular origin of FDCs. Gene coexpression within individual and highly enriched FDCs was determined using polymerase chain reaction. FDCs contain a very restricted mRNA pattern with high levels of message for the C3d receptor (CR2, Epstein Barr-virus/EBV receptor, CD21) and lack of mRNA for CD20, CD45, CD4, fibronectin, and platelet-derived growth factor receptor alpha and beta. These observations are consistent with the hypothesis that FDCs may not be of classical hematopoietic or fibroblastic origin. The absence of interferon-gamma, tumor necrosis factor-alpha, interleukin-3, and interleukin-6 mRNA provides preliminary evidence that these cells might produce only a very restricted set of cytokines limited to the germinal center.

Antigens, CD↗

PubMed1991

Thymus reticulum of autoimmune mice. 3. Ultrastructural study of NOD (non-obese diabetic) mouse thymus.

The non-obese diabetic (NOD) mouse develops spontaneous insulin-dependent diabetes mellitus. Converging lines of evidence indicate that the disease is of autoimmune origin and is primarily mediated by T cells. It thus appeared interesting to study the morphology of the thymic microenvironment in order to determine whether the architecture and/or the cellular components of the organ are altered. In the NOD mouse, significant aspects of involution were observed as early as the first month of life, forming a heterogeneous pattern with non-involuted areas. With time, these involuted aspects increased in surface and severity. In non-involuted zones vacuolization of epithelial cells was noted, as well as infiltration by plasma cells and the presence of numerous macrophages with high phagocytic activity. Involuted areas, forming a cellular layer as if cells had lost their limiting membranes, were crossed by a great number of cystic cavities bordered by epithelial cells and cells containing granulations. Their lumens contained lymphocytes and a few macrophages. These observations, which are reminiscent of similar reports made in other autoimmune mouse strains, may be related to the functional thymic abnormality thought to participate in the pathogenesis of autoimmune disease.

Animals↗

PubMed1996

Human osteoblasts support human hematopoietic progenitor cells in vitro bone marrow cultures.

Hematopoietic stem cell differentiation occurs in direct proximity to osteoblasts within the bone marrow cavity. Despite this striking affiliation, surprisingly little is known about the precise cellular and molecular impact of osteoblasts on the bone marrow microenvironment. Recently, we showed that human osteoblasts produce a variety of cytokine mRNAs including granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and interleukin-6. We examined here the ability of osteoblasts to support the development of hematopoietic colonies from progenitors as well the ability to maintain long-term culture-initiating cells (LTC-IC) in vitro. Examination of the hematopoietic cells recovered after 2 weeks of culture showed that osteoblasts support the maintenance of immature hematopoietic phenotypes. In methylcellulose assays, osteoblasts stimulate the development of hematopoietic colonies to a level at least 10-fold over controls from progenitor cells. Using limiting dilutional bone marrow cultures, we observed an activity produced by osteoblasts resulting in an threefold to fourfold expansion of human LTC-IC and progenitor cells in vitro. Thus, the presence of hematopoietic stem cells in close proximity to endosteal surfaces in vivo may be due in part to a requirement for osteoblast-derived products.

Adult↗

PubMed1983

Diffusion in the slice microenvironment and implications for physiological studies.

The brain cell microenvironment includes the extracellular space surrounding the cell together with the cellular elements that define the space. The dense packing of cells in the mammalian nervous system ensures that the extracellular space is narrow but highly complex in geometry. Recent studies with ion-selective micropipettes have revealed that the cerebellar slice can support changes in [K+]o that resemble those seen in the intact preparation. In the slice, [K+]o responses of individual cells can even be resolved. Studies with iontophoretic techniques and quantitative analysis in the slice have shown that the extracellular space has diffusion properties, characterized by a volume fraction and a tortuosity, that are very similar to those seen in the intact animal. These data confirm that the microenvironment in the slice is comparable to that in the intact animal. The diffusion parameters can be used to make predictions about the time necessary for substances to diffuse into slices under various conditions. Such estimates, together with other studies, indicate that it is probably inadvisable to use slices with thicknesses in excess of 300--400 micrometers, and that the bathing conditions can be critical in maintaining slice viability.

Animals↗

PubMed2003

Oxygen conformance of cellular respiration. A perspective of mitochondrial physiology.

Oxygen pressure declines from normoxic air-level to the microenvironment of mitochondria where cytochrome c oxidase (COX) reduces oxygen to water at oxygen levels as low as 0.3 kPa (2 Torr; 3 microM; 1.5 % air saturation). Intracellular hypoxia is defined as (1) local oxygen pressure below normoxic reference states, or (2) limitation of mitochondrial respiration by oxygen levels below kinetic saturation, resulting in oxyconformance. High-resolution respirometry provides the methodology to measure mitochondrial and cellular oxygen kinetics in the relevant low oxygen range < 1 kPa (7.5 mmHg; 9-10 microM; 5% air saturation). Respiration of isolated heart mitochondria follows hyperbolic oxygen kinetics with half-saturating oxygen pressure, p50, of 0.04 kPa (0.3 Torr; 0.4 microM) in ADP-stimulated state 3. Thus mitochondrial respiration proceeds at 90% of its hyperbolic maximum at the p50 of myoglobin, suggesting the possibility of a small but significant oxygen limitation even under normoxia in active muscle. Any impairment of oxygen delivery, therefore, induces oxyconformance. In addition, a shift of mitochondrial oxygen kinetics to the right, particularly by competitive inhibition of COX by NO, causes a further depression of respiration and a compensatory increase of local oxygen pressure. Above 1 kPa, mitochondrial oxygen uptake increases above hyperbolic saturation, which is probably due to oxygen radical production rather than the kinetics of COX. In cultured cells, the pronounced oxygen uptake above mitochondrial saturation at air-level oxygen pressure cannot be inhibited by rotenone and antimycin A, amounting to > 20 % of routine respiration in fibroblasts. Biochemical models of oxyconformance of COX are evaluated relative to patterns of intracellular oxygen distribution in the tissue and enzyme turnover in vivo, considering the kinetic effects of COX excess capacity on flux through the mitochondrial electron transport chain.

Animals↗

PubMed1990

Organization of the human immune system.

During the past decade, our knowledge concerning immunologic development and function has expanded rapidly as a result of the interplay between fundamental studies of antigen receptors and lymphokine molecules and the genes encoding them and studies of patients with leukemias, autoimmune disorders, and immunodeficiency diseases. The latter have been particularly valuable in defining the critical stages in the differentiation of stem cells into mature lymphoid effector cells and the roles played by different subpopulations of cells in regulating immune responses. Several categories of defects in these cellular maturation and cellular interaction events lead to immunodeficiency diseases, including intrinsic defects in the lymphoid cells; abnormalities in the microenvironments necessary for the generation of the differentiation signals essential for the maturation of lymphoid cells; disorders of regulatory cells that normally control humoral and cellular immune responses; and, finally, disorders in which the production of lymphoid cells and immunoglobulins is normal but in which host environment abnormalities lead to excessive endogenous catabolism or excessive loss of immune elements. A second area of major advance has been in defining the arrangement of immunoglobulin and T-cell receptor genes. These genes in their germline form are organized as discontinuous DNA elements that are joined by recombinations during lymphocyte development. The analysis of immunoglobulin gene structure and arrangement has contributed to the study of human lymphoid neoplasms. In addition, the analysis of rearranged immunoglobulin and T-cell receptor genes has been valuable in defining the lineage (T or B cell) of neoplasms whose origins were previously unknown; in determining the clonality of abnormal lymphocyte proliferation; in diagnosing and monitoring the therapy of lymphoid malignancies; in determining the state of maturation and the causes for failure of maturation of cells of the B-cell series; and in providing insights into the causes of malignant transformation of B and T lymphoid cells. It is apparent that the application of this molecular genetic approach has great potential for complementing conventional marker analysis, cytogenetics, and histopathology, thus broadening the scientific basis for the classification, diagnosis, and monitoring of the therapy of lymphoid neoplasia. A final area of dramatic advance has been in defining an array of lymphokine molecules that regulate T-cell and B-cell growth and differentiation. One of the best studied of these lymphokine systems is that of IL-2 and its receptor. Antigen-induced activation of resting T cells induces the synthesis of IL-2 as well as the expression of specific cell surface high-affinity receptors for this lymphokine.(ABSTRACT TRUNCATED AT 400 WORDS)

Gene Rearrangement, T-Lymphocyte↗

PubMed2005

Differential alteration of stem and other cell populations in ducts and lobules of TGFalpha and c-Myc transgenic mouse mammary epithelium.

Genes associated with proliferation are active in stem and progenitor cells, and their over-expression can promote cancer. Two such genes, c-Myc and TGFalpha, promote morphologically dissimilar mammary tumors in transgenic mice. We investigated whether their over-expression affects population size and cell cycle activity in stem and other cell populations in non-neoplastic mammary epithelia. Results indicated that both cell population and cell cycle regulation are cell type- and microenvironment-specific. To create a tool for identifying and categorizing the five cellular phenotypes by light microscopy, we adapted previously established ultrastructural criteria. Using nulliparous MMTV-c-myc or MT-tgfalpha mice, we determined and compared the relative sizes the putative stem, progenitor and differentiated cell populations. PCNA staining was used to compare the portion of each cell population in the cell cycle. Cell population sizes were analyzed relative to: (1) their location in ducts versus lobules (microenvironment), (2) genotype, and (3) cell type. Population sizes differed significantly by genotype, depending on microenvironment (p=0.0008), by genotype, depending on cell type (p<0.0001), and by microenvironment, depending on cell type (p=0.03). The number of cycling cells was also affected by all three factors, confirming that the interplay of cell type, gene expression and three-dimensional organization are very important in tissue morphogenesis and function. We describe a structure in mammary epithelium consistent with that of a stem cell niche, and show that it is altered in MMTV-c-myc and likely altered in MT TGFalpha transgenic epithelia.

Animals↗

PubMed1998

Phosphotransfer reactions in the regulation of ATP-sensitive K+ channels.

ATP-sensitive K+ (K(ATP)) channels are nucleotide-gated channels that couple the metabolic status of a cell with membrane excitability and regulate a number of cellular functions, including hormone secretion and cardioprotection. Although intracellular ATP is the endogenous inhibitor of K(ATP) channels and ADP serves as the channel activator, it is still a matter of debate whether changes in the intracellular concentrations of ATP, ADP, and/or in the ATP/ADP ratio could account for the transition from the ATP-liganded to the ADP-liganded channel state. Here, we overview evidence for the role of cellular phosphotransfer cascades in the regulation of K(ATP) channels. The microenvironment of the K(ATP) channel harbors several phosphotransfer enzymes, including adenylate, creatine, and pyruvate kinases, as well as other glycolytic enzymes that are able to transfer phosphoryls between ATP and ADP in the absence of major changes in cytosolic levels of adenine nucleotides. These phosphotransfer reactions are governed by the metabolic status of a cell, and their phosphotransfer rate closely correlates with K(ATP) channel activity. Adenylate kinase catalysis accelerates the transition from ATP to ADP, leading to K(ATP) channel opening, while phosphotransfers driven by creatine and pyruvate kinases promote ADP to ATP transition and channel closure. Thus, through delivery and removal of adenine nucleotides at the channel site, phosphotransfer reactions could regulate ATP/ADP balance in the immediate vicinity of the channel and thereby the probability of K(ATP) channel opening. In this way, phosphotransfer reactions could provide a transduction mechanism coupling cellular metabolic signals with K(ATP) channel-associated functions.

Adenosine Diphosphate↗

PubMed2004

An in vitro study on the mechanisms of coagulation activation in acute myelogenous leukemia (AML): role of tissue factor regulation by cytotoxic drugs and GM-CSF.

AML patients may suffer from a disseminated coagulopathy, which can aggravate a pre-existing bleeding tendency due to thrombocytopenia and platelet dysfunction. The cellular and molecular mechanisms underlying this coagulopathy, however, are not completely understood. Indeed, the broad and increasing therapeutic use of cytotoxic drugs and growth factors is likely to contribute to the complexity of hemostatic abnormalities encountered in this hematologic malignancy. The nature of coagulation activation in AML was therefore investigated in vitro using the human leukemic cell line, HL60. Tissue factor (TF) was almost entirely located on the cell surface and bound factor VIIa, but only 15-25% of this TF was primarily functionally active. Treatment with increasing concentrations of daunorubicin or cytosine-beta-D-arabinofuranoside, two cytotoxic drugs commonly used in AML therapy, induced apoptosis and secondary necrosis of HL60 cells and resulted in marked decryption of TF PCA independent of de novo protein synthesis. This PCA-modulating effect was concomitant with and functionally dependent on the exposure of phosphatidylserine on the outer membrane leaflet. Similar observations were made in analogous ex vivo studies on patient-derived myeloblasts. Incubation of HL60 cells with GM-CSF, a cytokine expressed in the bone marrow microenvironment and used as an adjunct to AML treatment, evoked a cellular response, which included both enhanced TF production and release of VEGF-A and uPA into the culture medium. We conclude that both decryption of pre-formed TF PCA by chemotherapeutic drugs and de novo induction of TF by cytokines such as GM-CSF can regulate the pro-coagulant phenotype of HL60 cells in vitro.

Antineoplastic Agents↗

PubMed2006

Acid-mediated tumor invasion: a multidisciplinary study.

The acid-mediated tumor invasion hypothesis proposes altered glucose metabolism and increased glucose uptake, observed in the vast majority of clinical cancers by fluorodeoxyglucose-positron emission tomography, are critical for development of the invasive phenotype. In this model, increased acid production due to altered glucose metabolism serves as a key intermediate by producing H(+) flow along concentration gradients into adjacent normal tissue. This chronic exposure of peritumoral normal tissue to an acidic microenvironment produces toxicity by: (a) normal cell death caused by the collapse of the transmembrane H(+) gradient inducing necrosis or apoptosis and (b) extracellular matrix degradation through the release of cathepsin B and other proteolytic enzymes. Tumor cells evolve resistance to acid-induced toxicity during carcinogenesis, allowing them to survive and proliferate in low pH microenvironments. This permits them to invade the damaged adjacent normal tissue despite the acid gradients. Here, we describe theoretical and empirical evidence for acid-mediated invasion. In silico simulations using mathematical models provide testable predictions concerning the morphology and cellular and extracellular dynamics at the tumor-host interface. In vivo experiments confirm the presence of peritumoral acid gradients as well as cellular toxicity and extracellular matrix degradation in the normal tissue exposed to the acidic microenvironment. The acid-mediated tumor invasion model provides a simple mechanism linking altered glucose metabolism with the ability of tumor cells to form invasive cancers.

Acidosis↗

PubMed2005

Stem cell regulation by the hematopoietic stem cell niche.

Both cellular as well as extracellular matrix components of the stem cell microenvironment, or niche, are critical in stem cell regulation. Recent data highlight a central role for osteoblasts and their by-product osteopontin as a key part of the hematopoietic stem cell (HSC) niche. Herein we describe a model for the yin and yang of HSC regulation mediated by osteoblasts. In this respect, osteoblasts synthesise proteins with opposing effects on HSC proliferation and differentiation highlighting their pivotal role in adult hematopoiesis. Although osteoblasts play a central role in HSC regulation other stromal and microenvironmental cell types and their extracellular matrix proteins also contribute to this biology. For example, the glycosaminoglycan hyaluronic acid as well as the membrane bound form of stem cell factor are also key regulators of HSC. Osteopontin and these "niche" molecules are not only involved in regulation of HSC quiescence but also effect HSC homing, trans-marrow migration and lodgement. Accordingly this leads us to expand upon Schofield's niche hypothesis: we propose that the HSC niche is critical for attraction of primitive hematopoietic progenitors to the endosteal region and tightly tethering them within this location, and by doing so placing them into intimate contact with cells such as osteoblasts whose cellular products are able to exquisitely regulate their fate.

Animals↗

PubMed1992

[Changes of microenvironment and tumor cell heterogeneity--consequences for bioptic diagnosis].

During the last several decades, immunohistochemical studies of tumors, along with other approaches, have suggested that the clinical and biological progression results, at least in part, from the sequential appearance within the neoplasm of cellular subpopulations whose new characteristics reflect specific somatic genetic changes. However, CNS may provide a different microenvironment for activation and proliferation than other tissues. The tissue-specific distribution of intermediate filament proteins, in particular the keratins, permits their use as marker in histopathology, but several important exceptions are recognized. In this connection, it is of interest that, according to the other reports, glial tumors may be positive for different anti-keratin antibodies. However, the gliomas did not show an immunoreaction in any of the cases when HEA-125 and Ber-EP4 were applied. The great number of multihormonal pituitary adenomas and possible change of the immunohistochemically detectable hormone status in cases of recurrent tumors have particularly re-emphasized the need for new thinking about patterns of classification. The diagnosis of malignant melanoma has been considerably facilitated recently by the introduction of immunohistological labelling with antibodies selective against melanoma antigen (HMB-45). Our results confirmed the necessity of cautious interpretation of HMB-45 immunoreactivity because a HMB-45 expression can be observed in several non-melanotic tumors.

Adenoma↗

PubMed2006

[The PAI-1 swing: microenvironment and cancer cell migration].

Cancer is a complex and dynamic process caused by a cellular dysfunction leading to a whole organ or even organism vital perturbation. To better understand this process, we need to study each one of the levels involved, which allows the scale change, and to integrate this knowledge. A matricellular protein, PAI-1, is able to induce in vitro cell behaviour modifications, morphological changes, and to promote cell migration. PAI-1 influences the mesenchymo-amaeboid transition. This matricellular protein should be considered as a potential 'launcher' of the metastatic process acting at the molecular, cellular, tissular levels and, as a consequence, at the organism's level.

Cell Adhesion↗