Biomedical subjects

N Chegini

Publications and source records attributed to N Chegini.

124 records · Page 7Linked to original sources

PubMed1984

Morphological and biochemical characterization of small and large bovine luteal cells during pregnancy.

Small (15-18 microns) and large (18-45 microns) luteal cells were obtained from bovine corpora lutea of pregnancy by centrifugal elutriation of enzymatically dispersed luteal cells. Small luteal cells accounted for about 85% and large luteal cells for 8-12% of total luteal cell population. Small luteal cells were characterized by a low cytoplasmic/nuclear ratio with cytoplasm containing mitochondria, lysosomes, lipid droplets, dense granules and endoplasmic reticulum. Large luteal cells possessed a higher cytoplasmic/nuclear ratio with cytoplasm containing more abundant mitochondria, lipid droplets, dense granules and lysosomes compared to small luteal cells. Some of the mitochondria were very long. Both small and large luteal cells contained scarce amounts of Golgi elements. Dense granules were found close to the nucleus in both cell types. The nucleus of both cell types was acentric, irregular in shape and contained a well-defined nucleolus. The highly condensed chromatin in small luteal cells was found at the nuclear periphery and in the central region. Dispersed chromatin was found throughout the nucleus with condensed chromatin at the nuclear periphery of large luteal cells. Macrophages and fibroblasts were occasionally found in small luteal cell preparations, but their morphology was quite distinct from both small and large luteal cells. Scanning electron microscopy revealed that the majority of the small and large luteal cells were spherical or slightly elongated in shape. Small luteal cells displayed the presence of blebs, ruffles and short microvilli. Large luteal cell surface contained ruffles and randomly distributed clusters of blebs of different sizes, predominantly spherical in shape with a smooth surface. Finger-like projections were also occasionally seen. Small luteal cells contained significantly lower amounts of protein, but the ratios between protein and DNA were similar in both cell types. The basal, human chorionic gonadotropin (hCG)- or cyclic AMP-stimulated progesterone production, the apparent dissociation constants for [125I]hCG binding and the apparent total number of available sites per cell were similar in small and large luteal cells. The activities of enzymes that are involved directly or indirectly in progesterone biosynthesis and those involved in general cellular metabolism and biosynthesis were also similar in small and large luteal cells with one exception. That is, the activities of 5'-nucleotidase and NADH cytochrome c reductase were significantly higher in small compared to large luteal cells.

5'-Nucleotidase↗

PubMed1984

Acute effects of mitoxantrone on the template activity of isolated nuclei from the T-47D human breast tumor cell line.

The effect of mitoxantrone on the template activity of nuclei isolated from the T-47D human breast tumor cell line was investigated. The results suggest that mitoxantrone significantly inhibits total RNA synthesis of these nuclei in a concentration-dependent manner. At low drug concentrations (10(-9) M and 10(-7) M) RNA synthesis was inhibited by 21.9% and 41% compared to control values, respectively. Greater inhibition was observed when the mitoxantrone concentration was increased to 10(-5) M or 10(-4) M (56% and 77%, respectively). Experiments utilizing alpha-amanitin revealed that mitoxantrone inhibits RNA polymerase II activity in a concentration-dependent manner.

Anthraquinones↗

PubMed1984

Binding sites for epidermal growth factor in human fetal membranes.

The present study demonstrates that human fetal membranes bind 125I-epidermal growth factor (125I-EGF), with chorion binding more than amnion. The chorion binding was also higher than that by decidua, but lower than in placenta. The lower binding by chorion compared to placenta was entirely attributable to a lower number of available EGF receptors and not to lower affinity. Chorion and placenta , but not amnion or decidua, from Cesarean section bound significantly more 125I-EGF when compared to tissues obtained after vaginal delivery. The binding of 125I-EGF to chorion exhibited dependency on time, temperature of incubation, pH of the incubation media, and amount of chorion protein. The 125I-EGF was not degraded during the binding reaction with chorion. The binding was specific in that unlabeled EGF inhibited 125I-EGF binding in a dose-dependent manner, whereas very high concentrations of other unlabeled hormones and growth factors had minimal effects on 125I-EGF binding. When some of these other hormones were tested for binding as tracers (125I-hCG, [3H]prostaglandin E1 and F2 alpha), neither chorion, amnion, decidua, nor placenta specifically bound these ligands. The 125I-EGF specific binding to chorion was saturable and a Scatchard plot of this data was curvilinear, which appears to be due to negative cooperativity. The apparent dissociation constant calculated from the initial slope of the plot was 0.20 nM, which is in excellent agreement with the concentration of unlabeled EGF required for half maximal inhibition of 125I-EGF binding, 0.26 nM. Autoradiography at the light microscope level revealed the presence of silver grains in amnion and chorion only when excess unlabeled EGF addition was withheld. The quantification of grains revealed the presence of a significantly (P less than 0.01) greater number of grains in chorion than in amnion, supporting the conclusion of the binding data. The physiological significance of EGF binding to fetal membranes and decidua is not known, but the considerable amount of EGF binding reported here suggests that they are target tissues for EGF.

Amnion↗

PubMed1983

Influence of mitoxantrone on nucleic acid synthesis on the T-47D breast tumor cell line.

Mitoxantrone exerts growth inhibitory effects, suppresses [3H]-thymidine as well as [3H]-uridine incorporation, and induces ultrastructural alterations in T-47D human breast tumor cells. At low concentration (10(-9)M) the drug induced little effect on cell proliferation; cell growth kinetics were inhibited at a concentration of 10(-5)M. [3H]-thymidine and [3H]-uridine incorporation declined rapidly at the concentrations tested (10(-9), 10(-7), and 10(-5) M), revealing a potent effect on metabolic activity of the cultured cells. The sharpest decline in DNA and RNA synthesis occurred within the first 2 hr of drug treatment. Serial ultrastructural examinations indicated definitive alterations in chromatin structure, disintegration of nucleolar components as early as 2 hr after drug treatment, and complete segregation of nucleolar components following 8-hr exposure to concentrations of the drug between 10(-5) and 10(-7) M. A distinct increase in the density of mitochrondrial matrix was evident. The in vitro data presented in this report demonstrate the growth inhibitory and antimetabolic effects of mitoxantrone on human breast tumor cells and suggest that the drug may be a promising antitumor agent.

Anthraquinones↗

PubMed1981

Structural transitions of chromatin in isolated Xenopus erythrocyte nuclei. I. The effects of ions.

Nuclei from Xenopus erythrocytes have been isolated under varying ionic conditions and their morphology studied by light and electron microscopy. The 200-A beaded chromatin fibre observed in vivo is maintained in media containing MgCl2 or CaCl2, but not in those containing Mn2+ as the sole divalent cation. In the absence of these alkaline-earth metal ions, 100-A filaments predominate. This suggests that the native 200-A fibre in isolated nuclei is also stabilized by specific divalent cations. Gross chromatin condensation within the nucleus occurs independently of whether the chromatin is in the form of 100-A or 200-A fibres, but requires the presence of divalent cations. Lower concentrations of MgCl2 or CaCl2 are necessary as compared with MnCl2. In the presence of sufficient divalent cations, decreasing KCl concentration causes peripheral condensation, the condensation of chromatin towards the nuclear membrane. Monovalent cation alone does not appear capable of inducing peripheral condensation. The transcriptional capacities of the different morphological types identified have been studied using E. coli RNA polymerase as a probe. Neither the degree of chromatin condensation nor the state of higher-order coiling have a significant effect on the rate of transcription of the DNA. These results are discussed with regard to further in vitro studies on eukaryotic gene activity.

Animals↗

PubMed1981

Structural transitions of chromatin in isolated Xenopus erythrocyte nuclei. II. Computer-based image analysis.

The morphology of isolated Xenopus erythrocyte nuclei is largely determined by the ionic constitution of the isolation medium. Electron microscopy of thin sections of nuclei isolated under varying ionic conditions has revealed four different morphological types with characteristic chromatin configurations. These nuclei have been used to study the condensation of chromatin within the confines of the nucleus. Electron micrographs of thin nuclear sections have been analysed by computer on the basis of their intensity of staining with lead citrate/uranyl acetate. The staining pattern (image analysis scan) is characteristic for each nuclear morphology and can be explained by a model which assumes that there are only four higher-order conformations that chromatin can adopt within the nucleus. These are present in varying amounts in the different nuclear types and an attempt has been made to equate the peaks identified by image analysis with previously-described chromatin structures. The results of this study serve to emphasize the potential of computer-based image analysis in the study of chromatin structure.

Animals↗

PubMed1980

Chromatin organization within nuclear blebs in leukocytes of Xenopus laevis.

The nuclei from leukocytes of peripheral blood, liver and spleen of an individual anaemic Xenopus laevis have been found to possess numerous nuclear blebs or projections. There structures were found to be very variable in size and shape as viewed in electron micrographs, but commonly included an enclosed mass of cytoplasm bound on one side by a very thin section of nuclear material. Such sections are membrane bounded on each side and frequently display an interesting ordered array of chromatin.

Animals↗

PubMed1979

Production and fate of erythroid cells in anaemic Xenopus laevis.

Adult Xenopus laevis, rendered anaemic by phenylhydrazine injection, have been studied during the recovery from such anaemia. Electron microscopy of liver and spleen sections indicates that both of these organs are active in the phagocytosis and destruction of the old damaged red blood cells. May-Grunwald and Giemsa staining of liver and spleen cells following anaemia has been used to show that erythropoiesis also occurs in both liver and spleen, and this has been confirmed by electron-microscope studies of these organs. Cell counting and radiolabelling of the new population of circulating erythroid cells in the period following phenylhydrazine injection suggests that a sudden release of basophilic erythroblasts from liver and spleen is followed by mitosis of this new cell population in circulation, and that no further release of erythroid cells from these organs is likely until complete recovery has occurred.

Anemia↗

PubMedDate not supplied

Peritoneal fluid cytokine and eicosanoid levels and their relation to the incidence of peritoneal adhesion.

OBJECTIVE: To determine the peritoneal fluid content of several cytokines and eicosanoids with inflammatory, anti-inflammatory, anti-fibrotic, and fibrotic activities, and to assess the relationship of these levels with the incidence of peritoneal adhesions. METHODS: Peritoneal fluids were collected from 30 subjects with adhesions (n = 22) or with normal pelvic anatomy (n = 8), and the level of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), interleukin-10 (IL-10), interferon gamma (IFN-gamma), transforming growth factor beta-1 (TGF-beta 1), granulocyte macrophage-colony stimulating factor (GM-CSF), prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and thromboxane B2 (TXB2) were determined by enzyme-linked immunosorbent assay (ELISA) and radioreceptor assay. RESULTS: The peritoneal fluid content of these factors varied considerably, with low levels of IL-1 beta, TNF-alpha, IL-10, IFN-gamma, and GM-CSF. Only IFN-gamma levels were significantly lower in subjects with adhesions compared with the normal group (P < .05). The levels of total (latent + active) and active TGF-beta 1 were higher than those of other cytokines assayed and were significantly higher in subjects with adhesions compared with the normal group (P < .05). The peritoneal fluid content of PGE2, TXB2, and LTB4 was significantly higher than that of the cytokines and was higher, but not significantly so, in subjects with adhesions compared with normal subjects (P = .06). CONCLUSION: Although the effect of length of time since the adhesions were formed is not known, the results indicate that peritoneal fluid content of these cytokines and eicosanoids, with the exception of IFN-gamma and TGF-beta 1, does not correlate with the presence of peritoneal adhesions.

Ascitic Fluid↗

PubMedDate not supplied

Differential expression of transforming growth factor-beta 1 and transforming growth factor-beta receptors in myometrium of women with failed induction of labor, no labor, and preterm labor.

OBJECTIVE: Comparative analysis of transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta receptor type I and type II messenger RNA (mRNA) and protein expression in myometrium of women who had unsuccessful labor induction, with those without labor or in preterm labor complicated by chorioamnionitis. METHODS: Small segments of myometrium were collected from women who were undergoing cesarean delivery for unsuccessful labor induction (n = 5), elective cesarean without labor (n = 5), or cesarean delivery for complications related to preterm labor and chorioamnionitis (n = 5). Total RNA was isolated from these tissues and subjected to competitive quantitative reverse-transcription-polymerase chain reaction (Q-RT-PCR) to determine the level of TGF-beta 1, and TGF-beta type I and type II receptor mRNA expression. Tissue sections were prepared from paraffin-embedded specimens and immunostained for TGF-beta 1 and receptor proteins using specific polycolonal antibodies. The data were analyzed by impaired Student t test and Kruskal-Wallis analysis of variance. RESULTS: Myometrium from women who had unsuccessful labor induction expressed higher levels of TGF-beta 1 mRNA (2.21 +/- 0.28 x 10(6) copies/microgram of total cellular RNA) than those with preterm labor (4.53 +/- 0.2 x 10(5) copies), or without labor [3.13 +/- 2.6 x 10(4) copies (P < .05)]. The level of TGF-beta type I receptor mRNA expression did not vary; however, type II receptor expression was significantly lower in myometrium from preterm labor (1.36 +/- 0.36 x 10(5) copies) compared with those from unsuccessful labor induction (3.42 +/- 0.42 x 10(6) copies) or without labor (9.65 +/- 3.2 x 10(5) copies). Immunoreactive TGF-beta 1 and TGF-beta receptor proteins were present in all myometrial tissues, and their intensity reflected that of the mRNA expression in these tissues. CONCLUSION: TGF-beta 1 and TGF-beta type II receptors are expressed differently in myometrium of women who had unsuccessful labor induction compared with those without labor or with preterm labor complicated by chorioamnionitis. Because TGF-beta is a key regulator of tissue remodeling which is central to initiation of normal labor, alterations in TGF-beta and/or TGF-beta receptor expression may lead to changes in the outcome of labor, at least at the myometrial level.

Cesarean Section↗

PubMedDate not supplied

Role of transforming growth factor beta-1 in peritonitis-induced adhesions.

Peritonitis is a major cause of intra-abdominal adhesion formation. The overexpression of transforming growth factor beta-1 (TGF-Beta1), a potent mitogen, chemoattractant, and stimulant for collagen synthesis by fibroblasts, has been linked to tissue fibrosis at various sites throughout the body including peritoneal adhesion formation. Hence we hypothesized that the mechanism(s) involved in peritonitis-induced adhesion formation may be mediated through the upregulation of TGF-Beta1 expression. Peritonitis was induced in rats by cecal ligation and puncture, while a control group underwent sham operation. Adhesions were scored and harvested from both groups at 0, 6 and 12 hours and at 1, 2, 4, 7, and 28 days. Tissue expression of TGF-Beta1 mRNA was determined by quantitative reverse transcription-polymerase chain reaction and TGF-Beta1 protein was localized by immunohistochemical analysis. Serum and peritoneal fluid TGF-Beta1 concentrations were quantified by enzyme-linked immunosorbent assay. Compared with sham operation, peritonitis was associated with a significantly greater incidence of abdominal adhesions and a significant increase in the levels of TGF-Beta1 mRNA expression at days 2, 4, and 7. Immunostaining intensity of TGF-Beta1 in adhesions from the peritonitis group also steadily rose through day 7. In peritoneal fluid, the ratio of active:total TGF-Beta1 was significantly increased in the peritonitis group on days 1, 2, and 4 compared with the sham group. These results suggest that peritonitis is associated with the upregulation of TGF-Beta1, a mechanism that may exacerbate adhesion formation.

Animals↗

PubMedDate not supplied

Surgical glove powders differentially modulate macrophage and lymphocyte-derived cytokines and eicosanoids production in vitro.

The objective of the present study was to determine the effect of surgical glove powders Biosorb, Keoflo, and CaCO(3) and Hydrocote (a powder-free film; Biogel) on cytokine and eicosanoid production by lipopolysaccharide/phorbol 12-myristate 13-acetate activated and unactivated HL60, U937, and RPMI 1788 cells, human monocyte/macrophage, and B lymphocyte cell lines. The unactivated cell culture-conditioned media contained a low level of interleukin-1alpha and -1beta, granulocyte macrophage colony stimulating factor, and tumor necrosis factor-alpha, which significantly increased after activation (p < 0.05). Exposure of unactivated cells to glove powders or Hydrocote (100 microg/ml) had little effect. However, these compounds appeared to have multiple inhibitory and stimulatory action on the production of these cytokines and eicosanoids in lipopolysaccharide/phorbol 12-myristate 13-acetate activated cells. For instance, granulocyte macrophage colony stimulating factor production was inhibited only in U937 cells by Keoflo and CaCO(3), whereas, tumor necrosis factor-alpha production was stimulated by Biosorb and Keoflo in HL-60, and CaCO(3) was found to be predominantly inhibitory on tumor necrosis factor-alpha production by these cells (p < 0.05). Total transforming growth factor-beta(1) production was stimulated by Biosorb and Hydrocote in U937 and HL-60 cells, respectively, but inhibited by Keoflo in U937 cells. However, Biosorb and Keoflo inhibited transforming growth factor-beta(1) production in both HL-60 and RPMI 1788 cells, without any effect on active transforming growth factor-beta(1). With regard to eicosanoids, Biosorb and Keoflo stimulated prostaglandin E(2) production by RPMI 1788 cells, whereas it was inhibited by all glove powders in HL-60 cells. Thromboxane B(2) production was stimulated by Keoflo and inhibited by CaCO(3) and Hydrocote in U937 cells. Finally, Leukotriene B(4) synthesis was found to become stimulated by Keoflo, CaCO(3), and Hydrocote in both HL60 and RPMI 1788 cells (p < 0.05). These data indicate that exposure of activated, but not unactivated, macrophages and lymphocyte to surgical glove powders and Hydrocote differentially effects the release of cytokines and eicosanoids by these cells. Considering that cytokines and eicosanoids play an important role in mediating the inflammatory and immune responses of wound healing, complications arising from glove powder exposure in vivo may involve mechanisms which alter the type and level of cytokine and eicosanoid production.

Journal Article↗

PubMedDate not supplied

Cellular distribution of 5-lipoxygenase and leukotriene receptors in postsurgical peritoneal wound repair.

Products of the eicosanoid pathways, namely prostaglandins and leukotrienes, are known to play a key role in inflammatory and immune responses, as well as other wound cellular activities of wounded tissue. The objective of this study was to determine whether surgically induced intraperitoneal and incisional wounds in the rat express 5-lipoxygenase and contain binding sites for leukotrienes and whether their levels change during the course of healing. With the use of a specific monoclonal antibody generated against 5-lipoxygenase, the enzyme was immunohistochemically localized in various wound cells during postsurgical days 2 to 35. The inflammatory cells within the wound were the major cell types containing 5-lipoxygenase immunoreactive protein, followed by fibroblasts in the incisional and peritoneal fibrous adhesions, striated muscle, and the vasculature. The greatest level of immunostaining was observed during the first 2 weeks after surgery, which decreased to near unwounded levels by day 35. Light microscope autoradiographic binding studies using (3)H-leukotrienes indicated that the peritoneal/incisional wounds and unwounded tissues contain specific (3)H-leukotriene C(4) and (3)H-leukotriene D(4) but not (3)H-leukotriene B(4) binding sites. Quantitative grain analysis (net grain density/100 microm(2)), representing specific (3)H-leukotriene C(4) and (3)H-leukotriene D(4) binding sites calculated for different cell types in the wound and unwounded regions showed that (3)H-leukotriene C(4) binding was highest over the striated muscle proximal to the injury and incisional and peritoneal granulation tissue fibroblasts. The net grain density over these cells increased by 3-, 2.5-, and 2-fold by day 14, respectively, and declined to the control values by day 21 after injury (p < 0.05). The pattern of (3)H-leukotriene D(4) binding was similar to that observed for (3)H-leukotriene C(4), but with a lower density. The grain density for (3)H-leukotriene C(4) and (3)H-leukotriene D(4) in arteriolar endothelial and smooth muscle cells remained unchanged. These data suggest that the products of the lipoxygenase pathway through the presence of their specific receptors may play an important role in peritoneal wound repair and adhesion formation.

Journal Article↗

PubMedDate not supplied

Expression of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases in mesothelial cells and their regulation by transforming growth factor-beta1.

Tissue injury and pelvic inflammation often results in peritoneal scar tissue formation. The objective of this study was to determine whether mesothelial cells which line the peritoneal cavity express matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs), and if their expression is regulated by transforming growth factor-beta1, a key regulator of tissue fibrosis. For this purpose we used Met-5A cells, a cell line derived from human normal mesothelial cells, and for comparative analysis we used U-937 cells, a human monocytic/macrophage cell line. The cells were treated with transforming growth factor-beta1 (1 ng/ml) for various time periods and the levels of MMP and TIMP mRNA and protein expression were determined using quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The results indicate that the mesothelial cells and macrophages express MMP-1 (collagenase-1), MMP-3 (stromelysin-1), TIMP-1 and TIMP-2 mRNA and protein at various levels, with significantly higher TIMPs than MMPs, and higher MMP-1 than MMP-3 (p < 0.001). The mesothelial cells express significantly less MMP-1, higher MMP- 3 and similar levels of TIMP mRNA compared to macrophages. In a time-dependent manner, treatment of the mesothelial cells with transforming growth factor-beta1 resulted in a significant decrease in the expression of MMP-1, while increasing the expression of TIMP-1 mRNA (p = 0.05). In contrast, MMP-3 and TIMP-2 expression was unaffected in mesothelial cells and in macrophages, compared to untreated controls. There was a significant increase in secreted MMP-1 and TIMP-2 by mesothelial cells following transforming growth factor-beta1 treatments in a time-dependent manner (p = 0.05 and p = 0.01), without affecting the secretion of these proteins by macrophages. A major portion of MMP-1 in the culture conditioned media of both cell types was found in complex with TIMP-1. The ratios of MMP-1/TIMPs production were significantly higher than MMP-3/TIMPs in mesothelial cells and macrophages, and progressively decreased following transforming growth factor-beta1 treatments (p < 0.05). In conclusion, these results indicate that mesothelial cells express MMP and TIMP mRNA and protein, and their expression is differentially regulated by transforming growth factor-beta1, a mechanism that in part may influence the outcome of peritoneal tissue repair and adhesion formation.

Analysis of Variance↗

PubMedDate not supplied

Alteration of type I and III collagen expression in human peritoneal mesothelial cells in response to hypoxia and transforming growth factor-beta1.

Overexpression and accumulation of extracellular matrix is central to peritoneal adhesion formation following surgically induced tissue trauma. Transforming growth factor-beta1 and hypoxia have been implicated in tissue fibrosis and postoperative adhesion formation. To extend this observation we examined whether transforming growth factor-beta1 and/or hypoxia regulate the expression of type I and III collagen in human peritoneal mesothelial cells. Cultured human mesothelial cells were maintained under hypoxia (2% oxygen), or treated with transforming growth factor-beta1 (1 ng/ml) or a combination of hypoxia and transforming growth factor-beta1. Total cellular RNA from treated and untreated cells were collected and subjected to multiplex reverse transcription/polymerase chain reaction to quantitate collagen I and III mRNA levels in response to these treatments. The results indicate that 6 hours of hypoxia increased collagen III mRNA by 7.2 fold which was further increased to 9.4 fold following transforming growth factor-beta1 treatment; in contrast collagen I mRNA decreased by 0.42 fold which was further decreased by 0.3 fold following transforming growth factor-beta1 treatment. Transforming growth factor-beta1 treatment under normal conditions resulted in an 8.4-fold increase and a 0.3-fold decrease in collagen III and I mRNA levels, respectively. Hypoxia treatment also resulted in a 1.9-fold increase in transforming growth factor-beta1 mRNA level compared with control. The ratio of type III/I collagen was increased in response to transforming growth factor-beta1 treatment under hypoxic condition. In conclusion, the data suggest that hypoxia may modulate extracellular matrix production by human mesothelial cells via a transforming growth factor-beta1 dependent mechanism.

Cell Hypoxia↗

PubMedDate not supplied

Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinase-3 and -4 in normal ovary and ovarian carcinoma.

The objective of this study was to determine the spatial expression of matrix metalloproteinases (MMPs) and their physiologic inhibitors, the tissue inhibitor of MMP (TIMP)-3 and TIMP-4, in ovarian carcinoma compared to normal ovaries. Immunohistochemistry was carried out in this study. Tissue sections prepared from normal ovarian tissues from throughout the menstrual cycle (N = 20) and ovarian carcinomas (N = 45) characterized as stage I (N = 5), stage III/IV (N = 40) were immunostained using polyclonal antibodies to the latent and the active form of MMP-26, TIMP-3, and a monoclonal antibody to TIMP-4. Immunoreactive MMP-26, TIMP-3, and TIMP-4 were detected in all the ovarian cell types in normal and tumor tissues. In normal ovarian tissues, theca externa and luteal cells immunostained with high intensity for MMP-26 and TIMPs while theca/granulosa cell staining intensity increased as lutenization progressed. There was low immunostaining of the ovarian stromal and surface epithelial cells for MMP-26, with moderate staining for TIMPs. In the carcinoma specimens, cancer cells and vascular endothelial cells displayed the highest staining intensity compared to adjacent nontumor areas. The immunostaining intensity of MMP-26 and TIMP-3 increased with stage of tumor with the invading tumor cells displaying the strongest immunostaining. MMP-26, TIMP-3, and TIMP-4 are expressed in normal ovarian as well as ovarian tumors with elevated expression in the invasive tumor cells suggesting a potential role for MMP-26 in normal ovary and ovarian cancer biologic function.

Aged↗