Chronic Ethanol Intake Promotes Double Gluthatione S-transferase/transforming Growth Factor-α-positive Hepatocellular Lesions In Male Wistar Rats

The chronic ethanol intake influence on the gluthatione S-transferase (GST-P) and transforming growth factor α (TGF-α) expression in remodeling/persistent preneoplastic lesions (PNLs) was evaluated in the resistant hepatocyte model. Male Wistar rats were allocated into five groups: G1, non-treated, fed water and chow ad libitum; G2, non-treated and pair-fed chow (restricted to match that of G3 group) and a maltodextrin (MD) solution in tap water (matched ethanol-derived calories); G3, fed 5% ethanol in drinking water and chow ad libitum; G4, diethylnitrosamine (DEN, 200 mg/kg, body weight) plus 200 parts per million of 2-acetylaminofluorene (2-AAF) for 3 weeks and pair-fed chow (restricted to match that of G5 group) and an MD solution in tap water (matched ethanol-derived calories); G5, DEN/2-AAF treatment, fed ethanol 5% and chow ad libitum. All animals were subjected to 70% partial hepatectomy at week 3 and sacrificed at weeks 12 or 22, respectively. Liver samples were collected for histological analysis or immunohistochemical expression of GST-P, TGF-α and proliferating cell nuclear antigen or zymography for matrix metalloproteinases-2 and-9. At the end of ethanol treatment, there was a significant increase in the percentage of liver area occupied by persistent GST-P-positive PNLs, the number of TGF-α-positive PNLs and the development of liver tumors in ethanol-fed and DEN/2-AAF-treated groups (G5 versus G4, P < 0.001). In addition, ethanol feeding led to a significant increase in cell proliferation mainly in remodeling and persistent PNLs with immunoreactivity for TGF-α at week 22 (P < 0.001). Gelatinase activities were not altered by ethanol treatment. The results demonstrated that ethanol enhances the selective growth of PNL with double expression of TGF-α and GST-P markers. © 2008 Japanese Cancer Association.992221228Pöschl, G., Seitz, H.K., Alcohol and cancer (2004) Alcohol Alcohol, 39, pp. 155-165Bofetta, P., Hashibe, M., Alcohol and cancer (2006) Lancet Oncol, 7, pp. 149-156Brown, L.M., Epidemiology of alcohol-associated cancers (2005) Alcohol, 35, pp. 161-168Voight, M.D., Alcohol in hepatocellular cancer (2005) Clin Liver Dis, 9, pp. 151-169Vidal, F., Toda, R., Gutiérrez, C., Influence of chronic alcohol abuse and liver disease on hepatic aldehyde dehydrogenase activity (1998) Alcohol, 15, pp. 3-8Lieber, C.S., Abittan, C.S., Pharmacology and metabolism of alcohol, including its metabolics effects and interactions with other drugs (1999) Clin Dermatol, 17, pp. 365-379Bunout, D., Nutritional and metabolic effects of alcoholism: Their relationship with alcoholic liver disease (1999) Nutrition, 15, pp. 583-589Niemellä, O., Distribution of ethanol-induced protein adducts in vivo: Relationship to tissue injury (2001) Free Rad Biol Med, 31, pp. 1533-1538Brooks, T.J., Theruvathu, J.A., DNA adducts from acetaldehyde: Implications for alcohol-related carcinogenesis (2005) Alcohol, 35, pp. 187-193Verna, L., Whysner, J., Williams, G.M., N-Nitrosodiethylamine mechanistic data and risk assessment: Bioactivation, DNA-Adduct formation, mutagenicity and tumor initiation (1996) Pharmacol Ther, 71, pp. 57-81Friedman, S.L., Mechanisms of disease: Mechanisms of hepatic fibrosis and therapeutic implication (2004) Nat Clin Pract Gastroenterol Hepatol, 1, pp. 98-105Purohit, V., Brenner, D.A., Mechanisms of alcohol-induced hepatic fibrosis: A summary of the Ron Thurman symposium (2006) Hepatology, 43, pp. 872-878Arthur, M.J.P., Fibrogenesis: Metalloproteinases and their inhibitors in liver fibrosis (2000) Am J Physiol Gastrointest Liver Phisiol, 279, pp. 245-249Tatsuta, M., Iishi, H., Baba, M., Enhancement by ethyl alcohol experimental hepatocarcinogenesis induced by N-nitrosomorpholine (1997) Int J Cancer, 71, pp. 1045-1048Karim, M.R., Wanibuchi, H., Wei, M., Morimura, K., Salim, E., Fukushima, S., Enhancing risk of ethanol on MeIQx-induced rat hepatocarcinogenesis is accompanied with increased levels of cellular proliferation and oxidative stress (2003) Cancer Lett, 192, pp. 37-47Kushida, M., Wanibuchi, H., Morimura, K., Dose-dependence of promotion of 2-amino-dimethylimidazo[4,5-f]quinoxaline-induced rat hepatocarcinogenesis by ethanol: Evidence for a threshold (2005) Cancer Sci, 96, pp. 747-757Stickel, F., Schuppan, D., Hahn, E.G., Seitz, H.K., Cocarcinogenic effects of alcohol in hepatocarcinogenesis (2002) Gut, 51, pp. 132-139Croager, E.J., Smith, P.G.J., Yeoh, G.C.T., Ethanol interactions with a choline-deficient, ethionine-supplemented feeding regime potentiate pre-neoplastic cellular alterations in rat liver (2002) Carcinogenesis, 23, pp. 1685-1693Wanibuchi, H., Wei, M., Karim, R., Existence of no hepatocarcinogenic effect levels of 2-amino-dimethylimidazo[4,5-f]quinoxaline with or without coadministration with ethanol (2006) Toxicol Pathol, 34, pp. 232-236Yanagi, S., Yamashita, M., Hiasa, Y., Kamiya, T., Effect of ethanol on hepatocarcinogenesis initiated in rats with 3′-methyl-4-dimethylaminoazobenzene in the absence of liver injuries (1989) Int J Cancer, 44, pp. 681-684Cho, K.J., Jang, J.J., Effects of carbon tetrachloride, ethanol, and acetaldehyde on diethylnitrosamine-induced hepatocarcinogenesis in rats (1993) Cancer Lett, 70, pp. 33-39Holmberg, B., Ekstrom, T., The effects of long-term oral administration of ethanol on Sprague-Dawley rats - A condensed report (1995) Toxicology, 96, pp. 133-145Solt, D., Farber, E., New principles for the analysis of chemical carcinogenesis (1976) Nature, 263, pp. 701-703Semple-Roberts, E., Hayes, M.A., Armstrong, D., Becker, R.A., Racz, W.J., Farber, E., Alternative methods of selecting hepatocellular nodules resistant to 2-acetylaminefluorene (1987) Int J Cancer, 40, pp. 643-645Tatematsu, M., Nagamine, Y., Farber, E., Redifferentiation as a basis for remodeling of carcinogen-induced hepatocyte nodules to normal appearing liver (1983) Cancer Res, 43, pp. 5049-5058Wood, G.A., Sarma, D.S.R., Archer, M.C., Resistance to the promotion of glutathione S-transferase 7-7-positive liver lesions in Copenhagen rats (1999) Carcinogenesis, 20, pp. 1169-1175Bannasch, P., Zerban, H., Predictive value of hepatic preneoplastic lesions as indicators of carcinogenic response (1992) Mechanism of Carcinogenesis in Risk Identification, pp. 389-427. , In: Vainio H, Magee PN, McGregor DB, McMichal AJ, eds. Lyon: IARC. Sci Publications, no. 116Pinheiro, F., Faria, R.R., de Camargo, J.L., Spinardi-Barbisan, A.L., da Eira, E.F., Barbisan, L.F., Chemoprevention of preneoplastic liver foci development by dietary mushroom Agaricus blazei Murrill in the rat (2003) Food Chem Toxicol, 41, pp. 1543-1550Schulte-Hermann, R., Kraupp-Grasl, B., Bursch, W., Gerbracht, U., Timmermann-Trosiener, I., Effects of non-genotoxic hepatocarcinogens phenobarbital and nafenopin on phenotype and growth of different populations of altered foci in rat liver (1989) Toxicol Pathol, 17, pp. 642-649Levin, S., Bucci, T.J., Cohen, S.M., The nomenclature of cell death: Recommendations of an ad hoc Committee of the Society of Toxicologic Pathologists (1999) Toxicol Pathol, 27, pp. 484-490Bradford, M.M., A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal Biochem, 72, pp. 248-254Bitsch, A., Hadjiolov, N., Klöhn, P.-C., Bergmann, O., Zwwirner-Baier, I., Neumann, H.-G., Dose-response of early effects related to tumor promotion of 2-acetylaminofluorene (2000) Toxicol Sci, 55, pp. 44-51Imai, T., Masui, T., Ichinose, M., Reduction of glutathione S-transferase P-form mRNA expression in remodeling nodules in rat liver revealed by in situ hybridization (1997) Carcinogenesis, 18, pp. 545-551De Miglio, M.R., Simile, M.M., Muroni, M.R., Phenotypic reversion of rat neoplastic liver nodules is under genetic control (2003) Int J Cancer, 105, pp. 70-75Kaufmann, W.K., Zhang, Y., Kaufmann, D.G., Association between expression of transforming growth factor-alpha and progression of hepatocellular foci to neoplasms (1992) Carcinogenesis, 13, pp. 1481-1483Tamano, S., Merlino, G.T., Ward, J.M., Rapid development of hepatic tumors in transforming growth factor alpha transgenic mice associated with increased cell proliferation in precancerous hepatocellular lesions initiated by N-nitrosodiethylamine and promoted by phenobarbital (1994) Carcinogenesis, 15, pp. 1791-1798Burr, A.W., Toole, K., Mathew, J., Hines, J.E., Chapman, C., Burt, A.D., Transforming growth factor-α expression is altered during experimental hepatocarcinogenesis (1996) J Pathol, 179, pp. 276-282Kitano, M., Wada, J., Ariki, Y., Possible tumour development from double positive foci for TGF-alpha and GST-P observed in early stages on rat hepatocarcinogenesis (2006) Cancer Sci, 97, pp. 478-483Sandgren, E.P., Luetteke, N.C., Qiu, T.H., Palmiter, R.D., Brinster, R.L., Lee, D.C., Transforming growth factor alpha dramatically enhances oncogene-induced carcinogenesis in transgenic mouse pancreas and liver (1993) Mol Cell Biol, 13, pp. 320-330Thorgeirsson, S.S., Santoni-Rugiu, E., Transgenic mouse models in carcinogenesis: Interaction of c-myc with transforming growth factor alpha and hepatocyte growth factor in hepatocarcinogenesis (1996) Br J Clin Pharmacol, 42, pp. 43-52Kato, J., Sato, Y., Inui, N., Ethanol induces transforming-growth factor-α expression in hepatocytes, leading to a stimulation of collagen synthesis by hepatic stellate cells (2003) Alcohol Clin Exp Res, 27, pp. 58S-63SZerban, H., Radig, S., Kopp-Schneider, A., Bannasch, P., Cell proliferation and cell death (apoptosis) in hepatic preneoplasia and neoplasia are closely related to phenotypic cellular diversity and instability (1994) Carcinogenesis, 15, pp. 2467-2473Grasl-Kraupp, B., Ruttkay-Nedecky, B., Müllauer, H., Taper, H., Huber, W., Bursch, W., Schulte-Hermann R Inherent increase of apoptosis in liver tumors: Implications for carcinogenesis and tumor regression (1997) Hepatology, 25, pp. 906-912Tanaka, T., Hirota, Y., Kuriyama, M., Nishiguchi, S., Otani, S., Time course of change in glutathione s-transferase positive foci and ornithine decarboxylase activity after cessation of long-term alcohol administration in rats (2001) Asian Pac J Cancer Prev, 2, pp. 131-134Mazzantini, R.P., de Conti, A., Moreno, F.S., Persistent and remodeling hepatic preneoplastic lesions present differences in cell proliferation and apoptosis, as well as in p53, Bcl-2 and NF-kappaB pathways (2007) J Cell BiochemFoda, H.D., Zucker, S., Matrix metalloproteinases in cancer invasion, metastasis and angiogenesis (2001) Drug Discov Today, 6, pp. 478-482Aye, M.M., Cuiling, M.A., Lin, H., Bower, K.A., Wiggins, R.C., Luo, J., Ethanol-induced in vitro invasion of breast cancer cells. the contribution of MMP-2 by fibroblasts (2004) Int J Cancer, 112, pp. 738-746Ke, Z., Lin, H., Fan, Z., MMP-2 mediates ethanol-induced invasion of mammary epithelial cells over-expressing ErbB2 (2006) Int J Cancer, 119, pp. 8-1

The Epiphyseal Cartilage And Growth Of Long Bones In Rana Catesbeiana

The structure of the epiphyseal cartilage of the bullfrog Rana catesbeiana and its role in the growth of long bones were examined. The epiphyseal cartilage was inserted into the end of a tubular bone shaft, defining three regions: articular cartilage, lateral articular cartilage and growth cartilage. Joining the lateral cartilage to the bone was a fibrous layer of periosteum, rich in blood vessels. Osteoblasts with alkaline phosphatase activity were found on the surface of the periosteal bone, which presented a fibrous non-mineralised tip. The growth cartilage was inside the bone. The proliferative chondrocytes presented perpendicular separation of daughter cells and there was no columnar arrangement of the cells. Furthermore, chondrocyte hypertrophy was not associated with either calcification or endochondral ossification, in apparent contrast to the avian and mammalian models. Finally, there was no reinforcement system capable of directing cell volume increase into longitudinal growth. Since bone extension depends on the intramembranous ossification of the periosteum, the growth cartilage is inside and not at the end of the bone and the cells in the growth cartilage show no columnar arrangement and separate in a direction perpendicular to the long bone axis, we conclude that the growth cartilage mainly contributes to the radial expansion of the bone.313301307Aceitero, J., Gaytan, F., Ranz, F.B., Ribes, R., Heterogeneity of the cartilage-marrow interface during uncalcified cartilage resorption in the chick embryo tibia (1988) J. Anat., 160, pp. 39-50Anderson, H.C., Mechanism of mineral formation in bone (1989) Lab. Invest., 60, pp. 1513-1520Bancroft, J. D. 1982Barreto, C., Albrecht, R.M., Bjorling, D.E., Horner, J.R., Wilsman, N.J., Evidence of the growth plate and the growth of long bones in juvenile dinosaurs (1993) Science, 262, pp. 2020-2023Bianco, P., Cancedda, F.D., Riminucci, M., Cancedda, R., Bone formation via cartilage models: The 'bordeline chondrocytes' (1998) Matrix Biol., 17, pp. 185-192Breur, G.J., Van Enkevort, B.A., Farnum, C.E., Wilsman, N.J., Linear relationship between the volume of hypertrophic chondrocytes and the rate of longitudinal bone growth in growth plates (1991) J. Orthop. Res., 9, pp. 348-359Breur, G.J., Farnum, C.E., Padgett, G.A., Wilsman, N.J., Cellular basis of decreased rate of longitudinal growth of bone in pseudoachondroplastic dogs (1992) J. Bone Jt. Surg., 74, pp. 516-528Breur, G.J., Lapierre, M.D., Kazmierczak, K., Stechuchak, K.M., McCabe, G.P., The domain of hypertrophic chondrocytes in growth plates growing at different rates (1997) Calcif. Tissue Int., 61, pp. 418-425Cancedda, R., Cancedda, F.D., Castagnola, P., Chondrocyte differentiation (1995) Int. Rev. Cytol., 159, pp. 265-359Carvalho, H.F., Understanding the biomechanics of tendon fibrocartilages (1995) J. Theor. Biol., 172, pp. 293-297Carvalho, H.F., Vidal, B.C., Structure and histochemistry of a pressure-bearing tendon of the frog (1994) Ann. Anat., 176, pp. 161-170Carvalho, H.F., Vidal, B.C., The unique fibrillar arrangement of the bullfrog pressure-bearing tendon as an indicative of great functional deformability (1994) Biol. Cell., 82, pp. 59-65Cole, A.A., Wezeman, F.H., Perivascular cells in cartilage canals of the developing mouse epiphysis (1985) Am. J. Anat., 174, pp. 119-129Cole, A.A., Wezeman, F.H., Cytochemical localization of tartrate-resistant acid phosphatase, alkaline phosphatase, and nonspecific esterase in perivascular cells of cartilage canals in the developing mouse epiphysis (1987) Am. J. Anat., 180, pp. 237-242Cotta-Pereira, G., Rodrigo, F.G., David-Ferreira, J.F., The use of tannic acid-glutaraldehyde in the study of elastic related fibers (1976) Stain Technol., 51, pp. 7-11Dell'Orbo, C., Gioglio, L., Quacci, D., Morphology of epiphyseal apparatus of a ranid frog (1992) Histol. Histopathol., 7, pp. 267-273Dickson, R.G., Ultrastruture of growth cartilage in the proximal femur of the frog, Rana temporaria (1982) J. Anat., 135, pp. 549-564Eggli, P.S., Herrmann, W., Hunziker, E.B., Schenk, R.K., Matrix compartments in the growth plate of the proximal tibia of rats (1985) Anat. Rec., 211, pp. 246-257Erlebacher, A., Filvaroff, E.H., Giltelman, S.E., Derynck, R., Toward a molecular understanding of skeletal development (1995) Cell, 80, pp. 371-378Farnum, C.E., Wilsman, N.J., Determination of proliferative characteristics of growth plate chondrocytes by labeling with bromodeoxyuridine (1993) Calcif. Tissue Int., 52, pp. 110-119Gardner, E., Gray, D.J., The prenatal development of the human femur (1970) Am. J. Anat., 129, pp. 121-140Haines, R.W., The evolution of epiphyses and of endochondral bone (1942) Biol. Rev., 17, pp. 267-292Hunziker, E.B., Schenk, R.K., Physiological mechanisms adopted by chondrocytes in regulating longitudinal bone growth in rats (1989) J. Physiol., 414, pp. 55-71Hunziker, E.B., Schenk, R.K., Cruz-Orive, L.M., Quantitation of chondrocyte performance in growth-plate cartilage during longitudinal bone growth (1987) J. Bone Jt. Surg., 69, pp. 162-173Lee, E.R., Lamplugh, L., Sherpard, N.L., Mort, J.S., The Septoclast, a cathepsin B-rich cell involved in the resorption of growth plate cartilage (1995) J. Histochem. Cytochem., 43, pp. 525-536Lewinson, D., Silbermann, M., Chondroclasts and endothelial cells collaborate in the process of cartilage resorption (1992) Anat. Rec., 233, pp. 504-514Mühlhauser, J., Resorption of the unmineralized proximal part of Meckel's cartilage in the rat (1986) A Light and Electron Microscopic Study. J. Submicrosc. Cytol. Pathol., 18, pp. 717-724Miyake, T., Cameron, A.M., Hall, B.K., Stage-specific expression patterns of alkaline phosphatase during development of the first arch skeleton in inbred C57BL/6 mouse embryos (1997) J. Anat., 190, pp. 239-260Rhodin, A.G., Comparative chondro-osseous development and growth of marine turtles (1985) Copeia, 3, pp. 752-771Schenk, R.K., Spiro, D., Wiener, J., Cartilage resorption in the tibial epiphyseal plate of growing rats (1967) J. Cell Biol., 34, pp. 275-291Shibata, S., Suzuki, S., Yamashita, Y., An ultrastructural study of cartilage resorption at the site of initial endochondral bone formation in the fetal mouse mandibular condyle (1997) J. Anat., 191, pp. 65-76Silvestrini, G., Ricordi, M.E., Bonucci, E., Resorption of uncalcified cartilage in the diaphysis of the chick embryo tibia (1979) Cell Tissue Res., 196, pp. 221-235Sorrell, J.M., Weiss, L., A light and electron microscopic study of the region of cartilage resorption in the embryonic chick (1980) Anat. Rec., 198, pp. 513-530Sorrell, J.M., Weiss, L., The cellular organization of fibroblastic cells and macrophages at regions of uncalcified cartilage resorption in the embryonic chick femur as revealed by alkaline and acid phosphatase histochemistry (1982) Anat. Rec., 202, pp. 491-499Speer, D.P., Collagenous architecture of the growth plate and perichondrial ossification groove (1982) J. Bone Jt. Surg., 64, pp. 399-407Thorp, B.H., Absence of cartilage canals in the long bone extremities of four species of skeletally immature marsupials (1990) Anat. Rec., 226, pp. 440-446Wilsman, N.J., Farnum, C.E., Lieferman, E.M., Fry, M., Barreto, C., Differential growth by growth plates as a function of multiple parameters of chondrocytic kinetics (1996) J. Orthop. Res., 14, pp. 927-93

Epithelial-stromal Transition Of Mmp-7 Immunolocalization In The Rat Ventral Prostate Following Bilateral Orchiectomy

Epithelial cells from involuting rat ventral prostate (VP) express Matrilysin (MMP-7) mRNA. Herein, we investigated by immunohistochemistry the MMP-7 protein location and its association with tissue changes following castration in the VP. Normal and castrated adult male Wistar rats were sacrificed at different times after surgery. VP was examined by immunocytochemistry and immunoprecipitation. Castration promoted a shrinking of prostate ducts with an extensive stromal remodeling. In the VP from normal rats, MMP-7 immunoreactivity was found in epithelial secretory granules. Three days after castration, immunostaining for MMP-7 was found in both the epithelial secretory granules and in the stroma just below the epithelium, mainly at the distal ductal tips. At seven and 21 days after castration, the immunostaining for MMP-7 was found only in the stromal space. Immunoprecipitation confirmed the specificity of the primary antibody by rescuing a pro-enzyme form (28 kDa) in the prostate extracts. The present results suggest that MMP-7 participates in the epithelial-stromal interface remodeling of the ventral prostate during the involution achieved by castration, probably in the degradation of components of the epithelial basement membrane. © 2007 International Federation for Cell Biology.311011731178Andreasen, P.A., Kristensen, P., Lund, L.R., Dano, K., Urokinase-type plasminogen activator is increased in the involuting ventral prostate of castrated rats (1990) Endocrinology, 126, pp. 2567-2576Antonioli, E., Della-Colleta, H.H., Carvalho, H.F., Smooth muscle cell behavior in the ventral prostate of castrated rats (2004) J Androl, 25, pp. 50-56Banerjee, P.P., Banerjee, S., Tilly, K.I., Tilly, J.L., Brown, T.R., Zirkin, B.R., Lobe-specific apoptotic cell death in rat prostate after androgen ablation by castration (1995) Endocrinology, 136, pp. 4368-4376Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal Biochem, 72, pp. 248-254Carvalho, H.F., Line, S.R.P., Basement membrane associated changes in the rat ventral prostate following castration (1996) Cell Biol Int, 20, pp. 809-819Carvalho, H.F., Vilamaior, P.S., Taboga, S.R., Elastic system of the rat ventral prostate and its modifications following orchiectomy (1997) Prostate, 32, pp. 27-34Geisler, S., Lichtinghagen, R., Boker, K.H., Veh, R.W., Differential distribution of five members of the matrix metalloproteinase family and one inhibitor (TIMP-1) in human liver and skin (1997) Cell Tissue Res, 289, pp. 173-183Haro, H., Crawford, H.C., Fingleton, B., Shinomiya, K., Spengler, D.M., Matrisian, L.M., Matrix metalloproteinase-7-dependent release of tumor necrosis factor-alpha in a model of herniated disc resorption (2000) J Clin Invest, 105, pp. 143-150Hashimoto, K., Kihira, Y., Matuo, Y., Usui, T., Expression of matrix metalloproteinase-7 and tissue inhibitor of metalloproteinase-1 in human prostate (1998) J Urol, 160, pp. 1872-1876Ilio, K.Y., Nemeth, J.A., Sensibar, J.A., Lang, S., Lee, C., Prostatic ductal system in rats: changes in regional distribution of extracellular matrix proteins during castration-induced regression (2000) Prostate, 43, pp. 3-10Imai, K., Hiramatsu, A., Fukushima, D., Pierschbacher, M.D., Okada, Y., Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-beta1 release (1997) Biochem J, 322, pp. 809-814Knox, J.D., Wolf, C., McDaniel, K., Clark, V., Loriot, M., Bowden, G.T., Matrilysin expression in human prostate carcinoma (1996) Mol Carcinog, 15, pp. 57-63Kwong, J., Choi, H.L., Huang, Y., Chan, F.L., Ultrastructural and biochemical observations on the early changes in apoptotic epithelial cells of the rat prostate induced by castration (1999) Cell Tissue Res, 298, pp. 123-136Kyprianou, N., Isaacs, J.T., Activation of programmed cell death in the rat ventral prostate after castration (1988) Endocrinology, 122, pp. 552-562Lee, C., Role of androgen in prostate growth and regression: stromal-epithelial interaction (1996) Prostate, 6, pp. 52-56Lee, C., Sensibar, J.A., Dudek, S.M., Hiipakka, R.A., Liao, S., Prostatic ductal system in rats: regional variation in morphological and functional activities (1990) Biol Reprod, 43, pp. 1079-1086Lynch, C.C., Hikosaka, A., Acuff, H.B., Martin, M.D., Kawai, N., Singh, R.K., MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL (2005) Cancer Cell, 7, pp. 485-496Marcotte, P.A., Kozan, I.M., Dorwin, S.A., Ryan, J.M., The matrix metalloproteinases Pump-1 catalyzes formation of low molecular weight (pro)urokinase in culture of normal human kidney cells (1992) J Biol Chem, 267, pp. 13803-13806Marker, P.C., Donjacour, A.A., Dahiya, R., Cunha, G.R., Hormonal, cellular, and molecular control of prostatic development (2003) Dev Biol, 253, pp. 165-174Matrisian, L.M., The matrix-degrading metalloproteinases (1992) Bioessays, 14, pp. 455-463McCawley, L.J., Matrisian, L.M., Matrix metalloproteinases: they're not just for matrix anymore! (2001) Curr Opin Cell Biol, 13, pp. 534-540Nemeth, H.A., Lee, C., Prostatic ductal system in rats: regional variation in stromal organization (1996) Prostate, 28, pp. 124-128Ouyang, X.S., Wang, X., Lee, D.T., Tsao, S.W., Wong, Y.C., Up-regulation of TRPM-2, MMP-7 and ID-1 during sex hormone-induced prostate carcinogenesis in the Noble rat (2001) Carcinogenesis, 22, pp. 965-973Powell, W.C., Knox, J.D., Navre, M., Grogan, T.M., Kittelson, J., Nagle, R.B., Expression of the metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice (1993) Cancer Res, 53, pp. 417-422Powell, W.C., Domann Jr., F.E., Mitchen, J.M., Matrisian, L.M., Nagle, R.B., Bowden, G.T., Matrilysin expression in the involuting rat ventral prostate (1996) Prostate, 29, pp. 159-168Powell, W.C., Fingleton, B., Wilson, C.L., Boothby, M., Matrisian, L.M., The metalloproteinase matrilysin proteolytically generates active soluble Fas ligand and potentiates epithelial cell apoptosis (1999) Curr Biol, 9, pp. 1441-1447Sang, Q.A., Bodden, M.K., Windsor, L.J., Activation of human progelatinase A by collagenase and matrilysin: activation of procollagenase by matrilysin (1996) J Protein Chem, 15, pp. 243-253Shiomi, T., Okada, Y., MT1-MMP and MMP-7 in invasion and metastasis of human cancers (2003) Cancer Metastasis Rev, 22, pp. 145-152Sugimura, Y., Cunha, G.R., Donjacour, A.A., Morphological and histological study of castration-induced degeneration and androgen-induced regeneration in the mouse prostate (1986) Biol Reprod, 34, pp. 973-983Terry, D.E., Clark, A.F., Influence of testosterone on chondroitin sulphate proteoglycan in the rat prostate (1996) Biochem Cell Biol, 74, pp. 645-651Udayakumar, T.S., Bair, E.L., Nagle, R.B., Bowden, G.T., Pharmacological inhibition of FGF receptor signaling inhibits LNCaP prostate tumor growth, promatrilysin, and PSA expression (2003) Mol Carcinog, 38, pp. 70-77Vilamaior, P.S., Felisbino, S.L., Taboga, S.R., Carvalho, H.F., Collagen fiber reorganization in the rat ventral prostate following androgen deprivation: a possible role for smooth muscle cells (2000) Prostate, 45, pp. 253-258Vilamaior, P.S., Taboga, S.R., Carvalho, H.F., Modulation of smooth muscle cell function: morphological evidence for a contractile to synthetic transition in the rat ventral prostate after castration (2005) Cell Biol Int, 29, pp. 809-816von Bredow, D.C., Cress, A.E., Howard, E.W., Bowden, G.T., Nagle, R.B., Activation of gelatinase-tissue-inhibitors-of-metalloproteinase complexes by matrilysin (1998) Biochem J, 331, pp. 965-972Wilson, C.L., Matrisian, L.M., Matrilysin: an epithelial matrix metalloproteinase with potentially novel functions (1996) Int J Biochem Cell Biol, 28, pp. 123-136Wilson, M.J., Strasser, M., Vogel, M.M., Sinha, A.A., Calcium-dependent and calcium-independent gelatinolytic proteinase activities of the rat ventral prostate and its secretion: characterization and effect of castration and testosterone treatment (1991) Biol Reprod, 44, pp. 776-785Wilson, M.J., Woodson, M., Wiehr, C., Reddy, A., Sinha, A.A., Matrix metalloproteinases in the pathogenesis of estradiol-induced nonbacterial prostatitis in the lateral prostate lobe of the Wistar rat (2004) Exp Mol Pathol, 77, pp. 7-17Woessner, J.F.J., Matrix metalloproteinases and their inhibitors in connective tissue remodeling (1991) FASEB J, 5, pp. 2145-2154Woessner, J.F.J., Taplin, C.J., Purification and properties of a small latent matrix metalloproteinase of the rat uterus (1988) J Biol Chem, 15, pp. 16918-1692

Metalloproteinases 2 And -9 Activity During Promotion And Progression Stages Of Rat Liver Carcinogenesis

Activity of metalloproteinases 2 and 9 (MMP-2 and 9) during promotion and progression of rat liver carcinogenesis was investigated in a modified resistant hepatocyte model. Development of preneoplastic liver lesions positive for glutathione S-transferase 7-7-(GST-P 7-7-positive PNL) and tumors besides hepatocytes positive for proliferating cell nuclear antigen (PCNA) were quantified and compared to MMP-2 and-9 activity using gelatin zymography. Marked increases in GST-P 7-7-positive PNL development, PCNA labeling indices, MMP-2 (pro, intermediate and active forms) and pro-MMP-9 activity were observed after proliferative stimulus induced by 2-acetylaminofluorene (2-AAF) exposure cycles. After 2-AAF withdrawal, increase in MMP-2 activity was detected only in neoplastic mixed lesions, whereas active MMP-9 was increased in both PLN and neoplastic tissues. Our findings suggest that MMP-2 may be associated with proliferative events induced by 2-AAF rather than with selective growth of PNL and that MMP-9 could be associated with progression of PNL and neoplastic mixed lesions. © 2008 Springer Science+Business Media B.V.401111Asamoto, M., Tsuda, H., Kagawa, M., De Camargo, J.L., Ito, N., Nagase, S., Strain differences in susceptibility to 2-acetylaminofluorene and phenobarbital promotion of rat hepatocarcinogenesis in a medium-term assay system: Quantitation of glutathione S-transferase P-positive foci development (1989) Jpn J Cancer Res, 80, pp. 939-944Bannasch, P., Zerban, H., Predictive value of hepatic preneoplastic lesions as indicators of carcinogenic response (1992) Mechanism of Carcinogenesis in Risk Identification 116, pp. 389-427. , IARC Sci Publ LyonBitsch, A., Hadjiolov, N., Klöhn, P.-C., Bergmann, O., Zwirner-Baier, I., Neumann, H.G., Dose response of early effects related to tumor promotion of 2-acetylaminofluorene (2000) Toxicol Sci, 55, pp. 44-51. , 10.1093/toxsci/55.1.44Brew, K., Dinakarpandian, D., Nagase, H., Tissue inhibitors of metalloproteinases: Evolution, structure and function (2000) Biochim Biophys Acta, 1477, pp. 267-283Caudroy, S., Polette, M., Nawrocki-Raby, B., Cao, J., Toole, B.P., Zucker, S., Birembaut, P., EMMPRIN-mediated MMP regulation in tumor and endothelial cells (2002) Clinical and Experimental Metastasis, 19 (8), pp. 697-702. , DOI 10.1023/A:1021350718226Chakraborti, S., Mandal, M., Das, S., Mandal, A., Chakraborti, T., Regulation of matrix metalloproteinases. An overview (2003) Molecular and Cellular Biochemistry, 253 (1-2), pp. 269-285. , DOI 10.1023/A:1026028303196Denda, A., Kitayama, W., Murata, A., Kishida, H., Sasaki, Y., Kusuoka, O., Tsujiuchi, T., Increased expression of cyclooxygenase-2 protein during rat hepatocarcinogenesis caused by a choline-deficient, l-amino acid-defined diet and chemopreventive efficacy of a specific inhibitor, nimesulide (2002) Carcinogenesis, 23, pp. 245-256. , 10.1093/carcin/23.2.245Farber, E., Sarma, D.S., Hepatocarcinogenesis: A dynamic cellular perspective (1987) Lab Investig, 56, pp. 4-22Foda, H.D., Zucker, S., Matrix metalloproteinases in cancer invasion, metastasis and angiogenesis (2001) Drug Discovery Today, 6 (9), pp. 478-482. , DOI 10.1016/S1359-6446(01)01752-4, PII S1359644601017524Gao, Y., Zhang, Z., Jiang, Z.-S., Fang, S.G., Sun, E.W., Wang, Y., Dynamic changes of matrix metalloproteinases in rat liver during the development of diethylnitrosamine-induced hepatocarcinoma (2002) Di Yi Jun Yi da Xue Xue Bao, 22, pp. 865-868Gianelli, G., Quaranta, V., Antonaci, S., Tissue remodelling in liver diseases (2003) Histol Histopathol, 18, pp. 1267-1274Gulbis, B., Alexandre, K., Galand, P., Quantitative and/or qualitative changes in the p21-H-ras post-translational products in regenerating liver and during hepatocarcinogenesis (1993) International Journal of Cancer, 55 (5), pp. 837-840. , DOI 10.1002/ijc.2910550524Hasegawa, R., Ito, N., Waalkes, M.P., Ward, J.M., Hepatocarcinogenesis in the rat (1994) Carcinogenesis, pp. 39-65. , Raven Press Ltd New YorkImaida, K., Tatematsu, M., Kato, T., Tsuda, H., Ito, N., Advantages and limitations of stereological estimation of placental glutathione S-transferase-positive rat liver cell foci by computerized three-dimensional reconstruction (1989) Jpn J Cancer Res, 80, pp. 326-330Kaneyoshi, T., Nakatsukasa, H., Higashi, T., Fujiwara, K., Naito, I., Nouso, K., Actual invasive potential of human hepatocellular carcinoma revealed by in situ gelatin zymography (2001) Clin Cancer Res, 7, pp. 4027-4032Kim, T.-H., Mars, W.M., Stolz, D.B., Michalopoulos, G.K., Expression and activation of pro-MMP-2 and pro-MMP-9 during rat liver regeneration (2000) Hepatology, 31, pp. 75-82. , 10.1002/hep.510310114Kinnitel, T., Mehde, M., Grundmann, A., Saile, B., Scharf, J.G., Ramadori, G., Expression of matrix metalloproteinases and their inhibitors during hepatic tissue repair in the rat (2000) Histochem Cell Biol, 113, pp. 443-453Lee, K.W., Kim, M.-S., Kang, N.J., Kim, D.-H., Surh, Y.-J., Lee, H.J., Moon, A., H-Ras selectively up-regulates MMP-9 and COX-2 through activation of EKK1/2 and NF-κB: An implication for invasive phenotype in rat liver epithelial cells (2006) International Journal of Cancer, 119 (8), pp. 1767-1775. , DOI 10.1002/ijc.22056Libbrecht, L., Desmet, V., Roskams, T., Preneoplastic lesions in human hepatocarcinogenesis (2005) Liver International, 25 (1), pp. 16-27. , DOI 10.1111/j.1478-3231.2005.01016.xMartinez-Hernandez, A., Amenta, P.S., The hepatic extracellular matrix I. Components and distribution in normal liver (1993) Virchows Arch A Pathol Anat Histopathol, 423, pp. 1-11. , 10.1007/BF01606425Pascale, R.M., Simile, M.M., De Miglio, M.R., Muroni, M.R., Calvisi, D.F., Asara, G., Casabona, D., Feo, F., Cell cycle deregulation in liver lesions of rats with and without genetic predisposition to hepatocarcinogenesis (2002) Hepatology, 35 (6), pp. 1341-1350. , DOI 10.1053/jhep.2002.33682Pinheiro, F., Faria, R.R., De Camargo, J.L.V., Spinardi-Barbisan, A.L.T., Da Eira, A.F., Barbisan, L.F., Chemoprevention of preneoplastic liver foci development by dietary mushroom Agaricus blazei Murrill in the rat (2003) Food and Chemical Toxicology, 41 (11), pp. 1543-1550. , DOI 10.1016/S0278-6915(03)00171-6Pires, P.W., Furtado, K.S., Justullin Jr., L.A., Rodrigues, M.A.M., Felisbino, S.L., Barbisan, L.F., Chronic ethanol intake promotes double gluthatione S-transferase/ transforming growth factor-α-positive hepatocellular lesions in male Wistar rats (2008) Cancer Science, 99 (2), pp. 221-228. , DOI 10.1111/j.1349-7006.2007.00677.xPitot, H.C., Pathways of progression in hepatocarcinogenesis (2001) Lancet, 358 (9285), pp. 859-860. , DOI 10.1016/S0140-6736(01)06038-XRa, H.-J., Parks, W.C., Control of matrix metalloproteinase catalytic activity (2007) Matrix Biology, 26 (8), pp. 587-596. , DOI 10.1016/j.matbio.2007.07.001, PII S0945053X0700090XRamaiah, S.K., A toxicologist guide to the diagnostic interpretation of hepatic biochemical parameters (2007) Food Chem Toxicol, 45, pp. 1551-1557. , 10.1016/j.fct.2007.06.007Sell, S., Dunsford, N.A., Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma (1989) Am J Pathol, 134, pp. 1347-1363Su, Q., Bannasch, P., Relevance of hepatic preneoplasia for human hepatocarcinogenesis (2003) Toxicologic Pathology, 31 (1), pp. 126-133. , DOI 10.1080/01926230309732Tiwawech, D., Hasegawa, R., Kurata, Y., Tatematsu, M., Shibata, M.A., Thamavit, W., Dose-dependent effects of 2-acetylaminofluorene on hepatic foci development and cell proliferation in rats (1991) Carcinogenesis, 12, pp. 985-990. , 10.1093/carcin/12.6.985Verna, L., Whysner, J., Williams, G.M., 2-Acetylaminofluorene mechanistic data and risk assessment: DNA reactivity, enhanced cell proliferation and tumor initiation (1996) Pharmacology and Therapeutics, 71 (1-2), pp. 83-105. , DOI 10.1016/0163-7258(96)00063-0Verna, L., Whysner, J., Williams, G.M., N-Nitrosodiethylamine mechanistic data and risk assessment: Bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation (1996) Pharmacology and Therapeutics, 71 (1-2), pp. 57-81. , DOI 10.1016/0163-7258(96)00062-9Vihinen, P., Ala-Aho, R., Kahari, V.-M., Matrix metalloproteinases as therapeutic targets in cancer (2005) Current Cancer Drug Targets, 5 (3), pp. 203-220. , DOI 10.2174/1568009053765799Visse, R., Nagase, H., Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function, and biochemistry (2003) Circulation Research, 92 (8), pp. 827-839. , DOI 10.1161/01.RES.0000070112.80711.3DWatanabe, T., Niioka, M., Hozawa, S., Kameyama, K., Hayashi, T., Arai, M., Ishikawa, A., Okazaki, I., Gene expression of interstitial collagenase in both progressive and recovery phase of rat liver fibrosis induced by carbon tetrachloride (2000) Journal of Hepatology, 33 (2), pp. 224-235. , DOI 10.1016/S0168-8278(00)80363-3Wood, G.A., Archer, M.C., Matrix metalloproteinases-2 and 9 do not play a role in the grotwth of preneoplastic liver lesions in F344 rats (2001) Exp Biol Med (Maywood), 226, pp. 799-803Xu, G.F., Li, P., Wang, X.Y., Jia, X., Tian, D.L., Jiang, L.D., Dynamic changes in the expression of matrix metalloproteinases and their inhibitors, TIMPs, during hepatic fibrosis induced by alcohol in rats (2004) World J Gastroenterol, 10, pp. 3621-3627Wang, D., Russell, J., Xu, H., Johnson, D.G., Regulation of cellular invasion and matrix metalloproteinase activity in HepG2 cell by connexin 26 transfection (2001) Molecular Carcinogenesis, 31 (2), pp. 101-109. , DOI 10.1002/mc.104

Implante de condrócitos homólogos em defeitos osteocondrais de cães: padronização da técnica e avaliação histopatológica

Padronizou-se a metodologia para cultura de condrócitos em cães e avaliou-se seu implante em lesões osteocondrais, utilizando-se a membrana biossintética de celulose (MBC) como revestimento. Dez cães, adultos e clinicamente sadios, foram submetidos à artrotomia das articulações fêmoro-tíbio-patelares. Defeitos de 4mm de diâmetro e profundidade foram induzidos no sulco troclear de ambos os membros. MBC foi aplicada na base e na superfície das lesões. Os defeitos do membro direito foram preenchidos com condrócitos homólogos cultivados formando o grupo-tratado (GT); os do membro esquerdo, sem implante celular, foram designados grupo-controle (GC). A evolução pós-operatória foi analisada com especial interesse nos processos de reparação da lesão, por meio de histomorfometria e imuno-histoquímica para colágeno tipo II e sulfato de condroitina. A cultura de condrócitos homólogos apresentou alta densidade e taxa de viabilidade. Observou-se integridade do tecido neoformado com a cartilagem adjacente na avaliação histológica, em ambos os grupos. Na imuno-histoquímica, verificou-se predomínio de colágeno tipo II no GT. Morfometricamente, não houve diferença significativa entre o tecido fibroso e o fibrocartilaginoso entre os grupos. A cultura de condrócitos homólogos de cães foi exequível. O tecido neoformado apresentou qualidade discretamente superior associado ao implante homólogo de condrócitos, contudo não promoveu reparação por cartilagem hialina

Implante de condrócitos homólogos em defeitos osteocondrais de cães: padronização da técnica e avaliação histopatológica Homologous articular chondrocytes implantation in osteochondral defects of dogs: technique and histopathological evaluation standardization

Padronizou-se a metodologia para cultura de condrócitos em cães e avaliou-se seu implante em lesões osteocondrais, utilizando-se a membrana biossintética de celulose (MBC) como revestimento. Dez cães, adultos e clinicamente sadios, foram submetidos à artrotomia das articulações fêmoro-tíbio-patelares. Defeitos de 4mm de diâmetro e profundidade foram induzidos no sulco troclear de ambos os membros. MBC foi aplicada na base e na superfície das lesões. Os defeitos do membro direito foram preenchidos com condrócitos homólogos cultivados formando o grupo-tratado (GT); os do membro esquerdo, sem implante celular, foram designados grupo-controle (GC). A evolução pós-operatória foi analisada com especial interesse nos processos de reparação da lesão, por meio de histomorfometria e imuno-histoquímica para colágeno tipo II e sulfato de condroitina. A cultura de condrócitos homólogos apresentou alta densidade e taxa de viabilidade. Observou-se integridade do tecido neoformado com a cartilagem adjacente na avaliação histológica, em ambos os grupos. Na imuno-histoquímica, verificou-se predomínio de colágeno tipo II no GT. Morfometricamente, não houve diferença significativa entre o tecido fibroso e o fibrocartilaginoso entre os grupos. A cultura de condrócitos homólogos de cães foi exequível. O tecido neoformado apresentou qualidade discretamente superior associado ao implante homólogo de condrócitos, contudo não promoveu reparação por cartilagem hialina.<br>The aim of the study is to standardize the methodology to achieve canine chondrocytes culture, and evaluate its implant on osteochondral defects made in the femoral trochlear sulcus of dogs, using the cellulose biosynthetic membrane (CBM) as coating. Ten healthy adult dogs without locomotor disorders were used. All animals were submitted to arthrotomy of stifle joints and defects of four millimeters in diameter x four millimeters deep were done in the femoral trochlear sulcus of both limbs. CBM were applied in the lesion base and surface of all limbs. In the treated group (TG), defects of the right limb were filled with cultivated homologous chondrocytes, and in control group (CG), defects of the left limb were left without cellular implant. Postoperative follow up was done by histomorphometry and Collagen type II and anti-chondroitin sulfate immunohistochemistry. The homologous chondrocytes culture showed high density and viability rate. Upon immunohistochemistry the predominance of type II collagen in extracellular matrix of TG was verified. However, no significant statistical difference was observed between the groups upon histomorphometry analysis of fibrous and fibrocartilaginous tissues. Canine homologous chondrocytes culture was practicable. Neoformed tissue showed slightly higher quality in TG, but without promoting repair by the hyaline cartilage

Protective Effect Of γ-tocopherol-enriched Diet On N-methyl-n-nitrosourea-induced Epithelial Dysplasia In Rat Ventral Prostate

Summary: Despite recent advances in understanding the biological basis of prostate cancer (PCa), the management of this disease remains a challenge. Chemoprotective agents have been used to protect against or eradicate prostate malignancies. Here, we investigated the protective effect of γ-tocopherol on N-methyl-N-nitrosourea (MNU)-induced epithelial dysplasia in the rat ventral prostate (VP). Thirty-two male Wistar rats were divided into four groups (n = 8): control (CT): healthy control animals fed a standard diet; control+γ-tocopherol (CT+γT): healthy control animals without intervention fed a γ-tocopherol-enriched diet (20 mg/kg); N-methyl-N-nitrosourea (MNU): rats that received a single dose of MNU (30 mg/kg) plus testosterone propionate (100 mg/kg) and were fed a standard diet; and MNU+γ-tocopherol (MNU+γT): rats that received the same treatment of MNU plus testosterone and were fed with a γ-tocopherol-enriched diet (20 mg/kg). After 4 months, the VPs were excised to evaluate morphology, cell proliferation and apoptosis, as well as cyclooxygenase-2 (Cox-2), glutathione-S-transferase-pi (GST-pi) and androgen receptor (AR) protein expression, and matrix metalloproteinase-9 (MMP-9) activity. An increase in the incidence of epithelial dysplasias, such as stratified epithelial hyperplasia and squamous metaplasia, in the MNU group was accompanied by augmented cell proliferation, GST-pi and Cox-2 immunoexpression and pro-MMP-9 activity. Stromal thickening and inflammatory foci were also observed. The administration of a γ-tocopherol-enriched diet significantly attenuated the adverse effects of MNU in the VP. The incidence of epithelial dysplasia decreased, along with the cell proliferation index, GST-pi and Cox-2 immunoexpression. The gelatinolytic activity of pro-MMP-9 returned to the levels observed for the CT group. These results suggest that γ-tocopherol acts as a protective agent against MNU-induced prostatic disorders in the rat ventral prostate. © 2013 International Journal of Experimental Pathology.946362372Banudevi, S., Elumalai, P., Sharmila, G., Arunkumar, R., Senthilkumar, K., Arunakaran, J., Protective effect of zinc on N-methyl-N-nitrosourea and testosterone-induced prostatic intraepithelial neoplasia in the dorsolateral prostate of Sprague Dawley rats (2011) Exp. Biol. Med., 236, pp. 1012-1021Barve, A., Khor, T.O., Nair, S., Gamma-tocopherol-enriched mixed tocopherol diet inhibits prostate carcinogenesis in TRAMP mice (2009) Int. J. Cancer, 124, pp. 1693-1999Beharka, A.A., Wu, D., Serafini, M., Meydani, S.N., Mechanism of vitamin E inhibition of cyclooxygenase activity in macrophages from old mice: role of peroxynitrite (2002) Free Radic. Biol. Med., 32, pp. 503-511Campbell, S., Stone, W., Whaley, S., Krishnan, K., Development of gamma (gamma)-tocopherol as a colorectal cancer chemopreventive agent (2003) Crit. Rev. Oncol. Hematol., 47, pp. 249-259Campbell, S.E., Musich, P.R., Whaley, S.G., Gamma tocopherol upregulates the expression of 15-S-HETE and induces growth arrest through a PPAR gamma-dependent mechanism in PC-3 human prostate cancer cells (2009) Nutr. Cancer, 61, pp. 649-662Campbell, S.E., Rudder, B., Phillips, R.B., γ-Tocotrienol induces growth arrest through a novel pathway with TGFβ2 in prostate cancer (2011) Free Radic. Biol. Med., 50, pp. 1344-1354Chandrasekharan, N.V., Simmons, D.L., The cyclooxygenases (2004) Genome Biol., 5, p. 241Cookson, M.S., Reuter, V.E., Linkov, I., Fair, W.R., Glutathione S-transferase PI (GST-pi) class expression by immunohisto-chemistry in benign and malignant prostate tissue (1997) J. Urol., 157, pp. 673-676Cunha, G.R., Donjacour, A., Stromal-epithelial interactions in normal and abnormal prostatic development (1987) Prog. Clin. Biol. Res., 239, pp. 251-272De Marzo, A.M., Marchi, V.L., Epstein, J.I., Nelson, W.G., Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis (1999) Am. J. Pathol., 155, pp. 1985-1992DeKlerk, D.P., Coffey, D.S., Quantitative determination of prostatic epithelial and stromal hyperplasia by a new technique biomorphometrics (1978) Invest. Urol., 16, pp. 240-245Gonçalves, B.F., Zanetoni, C., Scarano, W.R., Prostate carcinogenesis induced by N-methyl-N-nitrosourea (mnu) in gerbils: histopathological diagnosis and potential invasiveness mediated by extracellular matrix components (2010) Exp. Mol. Pathol., 88, pp. 96-106Griffiths, K., Prezioso, D., Turkes, A., Denis, L.J., The prevention of prostate cancer (2007) Recent Results Cancer Res., 175, pp. 33-63Guan, F., Li, G., Liu, A.B., δ- and γ-tocopherols, but not α-tocopherol, inhibit colon carcinogenesis in azoxymethane-treated F344 rats (2012) Cancer Prev. Res., 5, pp. 644-654Gunawardena, K., Murray, D.K., Meikle, A.W., Vitamin E and other antioxidants inhibit human prostate cancer cells through apoptosis (2000) Prostate, 44, pp. 287-295van Haaften, R.I., Haenen, G.R., Evelo, C.T., Bast, A., Tocotrienols inhibit human glutathione S-transferase P1-1 (2002) IUBMB Life, 54, pp. 81-84Hensley, K., Benaksas, E.J., Bolli, R., New perspectives on vitamin E: gamma-tocopherol and carboxyelthylhydroxychroman metabolites in biology and medicine (2004) Free Radic. Biol. Med., 36, pp. 1-15Jiang, Q., Elson-Schwab, I., Courtemanche, C., Ames, B.N., gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells (2000) Proc. Natl Acad. Sci. USA, 97, pp. 11494-11499Jiang, Q., Christen, S., Shigenaga, M.K., Ames, B.N., Gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention (2001) Am. J. Clin. Nutr., 74, pp. 714-722Jiang, Q., Wong, J., Ames, B.N., Gamma-tocopherol induces apoptosis in androgen-responsive LNCaP prostate cancer cells via caspase-dependent and independent mechanisms (2004) Ann. N. Y. Acad. Sci., 1031, pp. 399-400Jiang, F., Liao, Z., Hu, L.H., Comparison of antioxidative and antifibrotic effects of α-tocopherol with those of tocotrienol-rich fraction in a rat model of chronic pancreatitis (2011) Pancreas, 40, pp. 1091-1096Junqueira, L.C.U., Bignolas, G., Brentani, R.R., Picrosirius staining plus polarization microscopy, specific method of collagen detection in tissue sections (1979) Histochem. J., 11, pp. 447-455Kaina, B., Christmann, M., Naumann, S., Roos, W.P., Key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents (2007) DNA Repair, 6, pp. 1079-1099Katkoori, V., Manne, K., Vital-Reyes, V., Selective COX-2 inhibitor (celecoxib) decreases cellular growth in prostate cancer cell lines independent of p53 (2013) Biotech. Histochem., 88, pp. 38-46Kim, B.H., Kim, C.I., Chang, H.S., Cyclooxygenase-2 overexpression in chronic inflammation associated with benign prostatic hyperplasia: is it related to apoptosis and angiogenesis of prostate cancer? (2011) Korean J. Urol., 52, pp. 253-259Klein, E.A., Thompson Jr., I.M., Tangen, C.M., Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT) (2011) JAMA, 306, pp. 1549-1556Koh, C.M., Bieberich, C.J., Dang, C.V., Nelson, W.G., Yegnasubramanian, S., De Marzo, A.M., MYC and prostate cancer (2010) Genes Cancer, 1, pp. 617-628Koul, H.K., Kumar, B., Koul, S., The role of inflammation and infection in prostate cancer: importance in prevention, diagnosis and treatment (2010) Drugs Today, 46, pp. 929-943Kutchera, W., Jones, D.A., Matsunami, N., Prostaglandin H synthase 2 is expressed abnormally in human colon cancer: evidence for a transcriptional effect (1996) Proc. Natl Acad. Sci. USA, 93, pp. 4816-4820Kyprianou, N., Tu, H., Jacobs, S.C., Apoptotic versus proliferative activities in human benign prostatic hyperplasia (1996) Hum. Pathol., 27, pp. 668-675Lee, D.W., Sung, M.W., Park, S.W., Increased cyclooxygenase-2 expression in human squamous cell carcinomas of the head and neck and inhibition of proliferation by nonsteroidal anti-inflammatory drugs (2002) Anticancer Res., 22, pp. 2089-2096Liao, Z., Boileau, T.W., Erdaman Jr., J.W., Clinton, S.K., Interrelationships among angiogenesis, proliferation, and apoptosis in the tumor microenvironment during N-methyl-N-nitrosourea androgen-induced prostate carcinogenesis in rats (2002) Carcinogenesis, 23, pp. 1701-1711Lindshield, B.L., Ford, N.A., Canene-Adams, K., Diamond, A.M., Wallig, M.A., Erdman Jr., J.W., Selenium, but not lycopene or vitamin E, decreases growth of transplantable dunning R3327-H rat prostate tumors (2010) PLoS ONE, 5, pp. e10423Liu, X.H., Yao, S., Kirschenbaum, A., Levine, A.C., NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis and down-regulates bcl-2 expression in LNCaP cells (1998) Cancer Res., 58, pp. 4245-4249Lu, G., Xiao, H., Li, G.X., A gamma-tocopherol-rich mixture of tocopherols inhibits chemically induced lung tumorigenesis in A/J mice and xenograft tumor growth (2010) Carcinogenesis, 31, pp. 687-694Narayanan, N.K., Nargi, D., Horton, L., Reddy, B.S., Bosland, M.C., Narayanan, B.A., Inflammatory processes of prostate tissue microenvironment drive rat prostate carcinogenesis: preventive effects of celecoxib (2009) Prostate, 69, pp. 133-141Nemeth, J.A., Lee, C., Prostatic ductal system in rats: regional variation in stromal organization (1996) Prostate, 28, pp. 124-128Opdenakker, G., Van den Steen, P.E., Dubois, B., Gelatinase B functions as regulator and effector in leukocyte biology (2001) J. Leukoc. Biol., 69, pp. 851-859Parsons, J.K., Nelson, C.P., Gage, W.R., Nelson, W.G., Kensler, T.W., De Marzo, A.M., GSTA1 expression in normal, preneoplastic, and neoplastic human prostate tissue (2001) Prostate, 49, pp. 30-37Pruthi, R.S., Derksen, E., Gaston, K., Cyclooxygenase-2 as a potential target in the prevention and treatment of genitourinary tumors: a review (2003) J. Urol., 169, pp. 2352-2359Rinaldi, J.C., Justulin Jr., L.A., Lacorte, L.M., Implications of intrauterine protein malnutrition on prostate growth, maturation and aging (2013) Life Sci., 92, pp. 763-774Sarobo, C., Lacorte, L.M., Martins, M., Chronic caffeine intake increases androgenic stimuli, epithelial cell proliferation and hyperplasia in rat ventral prostate (2012) Int. J. Exp. Pathol., 93, pp. 429-437Shappell, S.B., Thomas, G.V., Roberts, R.L., Prostate pathology of genetically engineered mice: definitions and classification. The consensus report from the Bar Harbor meeting of the mouse models of human cancer consortium prostate pathology committee (2004) Cancer Res., 64, pp. 2270-2305Smolarek, A.K., So, J.Y., Thomas, P.E., Dietary tocopherols inhibit cell proliferation, regulate expression of ERα, PPARγ, and Nrf2, and decrease serum inflammatory markers during the development of mammary hyperplasia (2013) Mol. Carcinog., 52, pp. 514-525Stephenson, A.J., Abouassaly, R., Klein, E.A., Chemoprevention of prostate cancer (2010) Urol. Clin. North Am., 37, pp. 11-21Strope, S.A., Andriole, G.L., Update on chemoprevention for prostate cancer (2010) Curr. Opin. Urol., 20, pp. 194-197Syed, D.N., Khan, N., Afaq, F., Mukhtar, H., Chemoprevention of prostate cancer through dietary agents: progress and promise (2007) Cancer Epidemiol. Biomarkers Prev., 16, pp. 2193-2203Takahashi, S., Takeshita, K., Seeni, A., Suppression of prostate cancer in a transgenic rat model via gamma-tocopherol activation of caspase signaling (2009) Prostate, 69, pp. 644-651Tasanarong, A., Kongkham, S., Thitiarchakul, S., Eiam-Ong, S., Vitamin E ameliorates renal fibrosis in ureteral obstruction: role of maintaining BMP-7 during epithelial-to-mesenchymal transition (2011) J. Med. Assoc. Thai., 94 (7 SUPPL), pp. S10-S18Thapa, D., Ghosh, R., Antioxidants for prostate cancer chemoprevention: challenges and opportunities (2012) Biochem. Pharmacol., 83, pp. 1319-1330Torricelli, P., Caraglia, M., Abbruzzese, A., Beninati, S., γ-Tocopherol inhibits human prostate cancer cell proliferation by up-regulation of transglutaminase 2 and down-regulation of cyclins (2013) Amino Acids, 44, pp. 45-51Traber, M.G., Vitamin E regulatory mechanisms (2007) Annu Rev Nutr., 27, pp. 347-362Wilson, M.J., Woodson, M., Wiehr, C., Reddy, A., Sinha, A.A., Matrix metalloproteinases in the pathogenesis of estradiol-induced nonbacterial prostatitis in the lateral prostate lobe of the Wistar rat (2004) Exp. Mol. Pathol., 77, pp. 7-17Xie, W., Wong, Y.C., Tsao, S.W., Correlation of increased apoptosis and proliferation with development of prostatic intraepithelial neoplasia (PIN) in ventral prostate of the noble rat (2000) Prostate, 44, pp. 31-39Yang, C.S., Suh, N., Kong, A.N., Does vitamin E prevent or promote cancer? (2012) Cancer Prev. Res., 5, pp. 701-705Yoshikawa, S., Morinobu, T., Hamamura, K., Hirahara, F., Iwamoto, T., Tamai, H., The effect of gamma-tocopherol administration on alpha-tocopherol levels and metabolism in humans (2005) Eur. J. Clin. Nutr., 59, pp. 900-905Zhang, M., Altuwaijri, S., Yeh, S., RRR-alpha-tocopheryl succinate inhibits human prostate cancer cell invasiveness (2004) Oncogene, 23, pp. 3080-308

Ethanol Modulates The Synthesis And Catabolism Of Retinoic Acid In The Rat Prostate

All-trans retinoic acid (atRA) maintains physiological stability of the prostate, and we reported that ethanol intake increases atRA in the rat prostate; however the mechanisms underlying these changes are unknown. We evaluated the impact of a low- and high-dose ethanol intake (UChA and UChB strains) on atRA metabolism in the dorsal and lateral prostate. Aldehyde dehydrogenase (ALDH) subtype 1A3 was increased in the dorsal prostate of UChA animals while ALDH1A1 and ALDH1A2 decreased in the lateral prostate. In UChB animals, ALDH1A1, ALDH1A2, and ALDH1A3 increased in the dorsal prostate, and ALDH1A3 decreased in the lateral prostate. atRA levels increased with the low activity of CYP2E1 and decreased with high CYP26 activity in the UChB dorsal prostate. Conversely, atRA was found to decrease when the activity of total CYP was increased in the UChA lateral prostate. Ethanol modulates the synthesis and catabolism of atRA in the prostate in a concentration-dependent manner.5319Fields, A.L., Soprano, D.R., Soprano, K.J., Retinoids in biological control and cancer (2007) J Cell Biochem, 102, pp. 886-898Altucci, L., Leibowitz, M.D., Ogilvie, K.M., de Lera, A.R., Gronemeyer, H., RAR and RXR modulation in cancer and metabolic disease (2007) Nat Rev Drug Discov, 6, pp. 793-810Kane, M.A., Folias, A.E., Wang, C., Napoli, J.L., Ethanol elevates physiological all-trans retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity (2010) FASEB J, 24, pp. 823-832Lasnitzki, I., Goodman, D.S., Inhibition of the effects of methylcholanthrene on mouse prostate in organ culture by vitamin A and its analogs (1974) Cancer Res, 34, pp. 1564-1571Vezina, C.M., Allgeier, S.H., Fritz, W.A., Moore, R.W., Strerath, M., Bushman, W., Retinoic acid induces prostatic bud formation (2008) Dev Dyn, 237, pp. 1321-1333Pöschl, G., Seitz, H.K., Alcohol and cancer (2004) Alcohol Alcohol, 39, pp. 155-165Alizadeh, F., Bolhassani, A., Khavari, A., Bathaie, S.Z., Naji, T., Bidgoli, S.A., Retinoids and their biological effects against cancer (2014) Int Immunopharmacol, 18, pp. 43-49Kumar, S., Sandell, L.L., Trainor, P.A., Koentgen, F., Duester, G., Alcohol and aldehyde dehydrogenases: retinoid metabolic effects in mouse knockout models (2011) Biochim Biophys Acta, 1821, pp. 198-205Molotkov, A., Duester, G., Retinol/ethanol drug interaction during acute alcohol intoxicationin mice involves inhibition of retinol metabolism to retinoic acidby alcohol dehydrogenase (2002) J Biol Chem, 277, pp. 22553-22557Lee, M.O., Manthey, C.L., Sladek, N.E., Identification of mouse liver aldehyde dehydrogenases that catalyze the oxidation of retinaldehyde to retinoic acid (1991) Biochem Pharmacol, 42, pp. 1279-1285Vasiliou, V., Pappa, A., Estey, T., Role of human aldehyde dehydrogenases in endobiotic and xenobiotic metabolism (2004) Drug Metab Rev, 36, pp. 279-299Ross, A.C., Zolfaghari, R., Cytochrome P450s in the regulation of cellular retinoic acid metabolism (2011) Annu Rev Nutr, 31, pp. 65-87Chithalen, J.V., Luu, L., Petkovich, M., Jones, G., HPLC-MS/MS analysis of the products generated from all-trans-retinoic acid using recombinant human CYP26A (2002) J Lipid Res, 43, pp. 1133-1142Taimi, M., Helvig, C., Wisniewski, J., Ramshaw, H., White, J., Amad, M., A novel human cytochrome P450, CYP26C1, involved in metabolism of 9-cis and all-trans isomers of retinoic acid (2004) J Biol Chem, 279, pp. 77-85Chung, J., Veeramachaneni, S., Liu, C., Mernitz, H., Russell, R.M., Wang, X.D., Vitamin E supplementation does not prevent ethanol-reduced hepatic retinoic acid levels in rats (2009) Nutr Res, 29, pp. 664-670Liu, C., Russell, R.M., Seitz, H.K., Wang, X.D., Ethanol enhances retinoic acid metabolism into polar metabolites in rat liver via induction of cytochrome P450 2E1 (2001) Gastroenterology, 120, pp. 179-189Lieber, C.S., De Carli, L.M., Hepatotoxicity of ethanol (1991) J Hepathol, 12, pp. 394-401Wang, X.D., Chronic alcohol intake interferes with retinoid metabolism and signaling (1999) Nutr Rev, 57, pp. 51-59Chung, J., Liu, C., Smith, D.E., Seitz, H.K., Russell, R.M., Wang, X.D., Restoration of retinoic acid concentration supressesethanolenhanced c-Jun expression and hepatocyte proliferation in rat liver (2001) Carcinogenesis, 22, pp. 1213-1219Fontanelli, B.A.F., Chuffa, L.G.A., Teixeira, G.R., Amorim, J.P.A., Mendes, L.O., Pinheiro, P.F.F., Chronic ethanol consumption alters all-trans-retinoic acid concentration and expression of their receptors on the prostate: a possible link between alcoholism and prostate damage (2013) Alcohol Clin Exp Res, 37, pp. 49-56Pasquali, D., Thaller, C., Eichele, G., Abnormal level of retinoic acid in prostate cancer tissues (1996) J Clin Endocrinol Metab, 81, pp. 2186-2191Richter, F., Joyce, A., Fromowitz, F., Wang, S., Watson, J., Watson, R., Immunohistochemical localization of the retinoic acid receptors in human prostate (2002) J Androl, 23, pp. 830-838Mardones, J., Segovia-Riquelmi, N., Thirty-two years of rats by ethanol preference: UChA and UChB strains (1983) Neuro Behav Toxicol Teratol, 5, pp. 171-178Quintanilla, M.E., Israel, Y., Sapag, A., Tampier, L., The UChA and UChB rat lines: metabolic and genetic differences influencing ethanol intake (2006) Addict Biol, 11, pp. 310-323Chuffa, L.G., Fioruci-Fontanelli, B.A., Mendes, L.O., Fávaro, W.J., Pinheiro, P.F., Martinez, M., Characterization of chemically induced ovarian carcinomas in an ethanol-preferring rat model: influence of long-term melatonin treatment (2013) PLoS One, 8, p. e81676Chuffa, L.G., Seiva, F.R., Fávaro, W.J., Amorim, J.P., Teixeira, G.R., Mendes, L.O., Melatonin and ethanol intake exert opposite effects on circulating estradiol and progesterone and differentially regulate sex steroid receptors in the ovaries, oviducts, and uteri of adult rats (2013) Reprod Toxicol, 39, pp. 40-49Chuffa, L.G., Amorim, J.P., Teixeira, G.R., Mendes, L.O., Fioruci, B.A., Pinheiro, P.F., Long-term exogenous melatonin treatment modulates overall feed efficiency and protects ovarian tissue against injuries caused by ethanol-induced oxidative stress in adult UChB rats (2011) Alcohol Clin Exp Res, 35, pp. 1498-1508Chuffa, L.G., Seiva, F.R., Fávaro, W.J., Teixeira, G.R., Amorim, J.P., Mendes, L.O., Melatonin reduces LH, 17 beta-estradiol and induces differential regulation of sex steroid receptors in reproductive tissues during rat ovulation (2011) Reprod Biol Endocrinol, 9, p. 108Guo, X., Knudsen, B.S., Peehl, D.M., Ruiz, A., Bok, D., Rando, R.R., Retinol metabolism and lecithin: retinol acyltransferase levels are reduced in cultured human prostate cancer cells and tissue specimens (2002) Cancer Res, 62, pp. 1654-1661Kim, H., Lapointe, J., Kaygusuz, G., Ong, D., Li, C., Rijn, M.V., The retinoic acid synthesis gene ALDH1a2 is a candidate tumor suppressor in prostate cancer (2005) Cancer Res, 65, pp. 8118-8124Reichman, M.E., Hayes, R.B., Ziegler, R.G., Schatzkin, A., Taylor, P.R., Kahle, L.L., Serum vitamin A and subsequent development of prostate cancer in the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (1990) Cancer Res, 50, pp. 2311-2315Touma, S.E., Perner, S., Rubin, M.A., Nanus, D.M., Gudas, L.J., Retinoid metabolism and ALDH1A2 (RALDH2) expression are altered in the transgenic adenocarcinoma mouse prostate model (2009) Biochem Pharmacol, 78, pp. 1127-1138Shmueli, O., Horn-Saban, S., Chalifa-Caspi, V., Shmoish, M., Ophir, R., Benjamin-Rodrig, H., GeneNote: wholegenome expression profiles in normal human tissues (2003) C R Biol, 326, pp. 1067-1072Su, A.I., Wiltshire, T., Batalov, S., Lapp, H., Ching, K.A., Block, D., A gene atlas of the mouse and human protein-encoding transcriptomes (2004) Proc Natl Acad Sci USA, 101, pp. 6062-6067McSorley, L.C., Daly, A.K., Identification of human cytochrome P450 isoforms that contribute to all-trans-retinoic acid 4-hydroxylation (2000) Biochem Pharmacol, 60, pp. 517-526Roberts, E.S., Vaz, A.D.N., Coon, M.J., Role of isozymes of rabbit microsomal cytochrome P-450 in the metabolism of retinoic acid, retinol, and retinal (1992) Mol Pharmacol, 41, pp. 427-433Abu-Abed, S., Dolle, P., Metzger, D., The retinoic acid-metabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity, and development of posteriorstructures (2001) Genes Dev, 15, pp. 226-24

Plasma rico em plaquetas no tratamento de lesões condrais articulares induzidas experimentalmente em equinos: avaliação clínica, macroscópica, histológica e histoquímica

Estudou-se a eficácia do plasma rico em plaquetas (PRP) no tratamento de lesões condrais articulares, experimentalmente induzidas em equinos. Para isso, foi induzida uma lesão condral, na tróclea medial femoral dos dois membros pélvicos de quatro animais. Após 30 dias da indução, as oito articulações foram divididas em dois grupos. Os animais do grupo 1 receberam o tratamento intralesional e intra-articular com PRP, e os do grupo 2 foram tratados apenas com solução fisiológica. As avaliações clínicas, constituídas de exames de claudicação e análises do líquido sinovial, foram realizadas antes da indução da lesão - tempo zero -, quinzenalmente, até 120 dias e aos 150 dias. Avaliações macroscópicas, histológicas e histoquímicas foram realizadas no tempo zero e aos 150 dias. Os equinos do grupo 1 apresentaram melhora do grau de claudicação em relação aos do grupo 2. Os exames macroscópicos, histológicos e histoquímicos revelaram melhor tecido de reparação igualmente no grupo 1. Concluiu-se que a administração de PRP apresentou efeitos benéficos no tratamento de lesões condrais experimentais de equinos.The use of platelet-rich plasma (PRP) in the treatment of articular cartilage defects induced experimentally in horses was studied. For this purpose, both patellofemoral joints of four animals were approached through arthroscopic surgery to perform a cartilage defect on the medial femoral trochlea. After 30 days of induction the eight joints were divided into two groups. Group 1 animals received intralesional and intra-articular treatment with PRP and Group 2 animals were treated only with saline solution. The clinical assessments, constituted by lameness signs and synovial fluid analysis, were performed before induction of injury (time zero) and every 15 days in 120 days, with last analysis on day 150. The macroscopic and morphologic analysis were performed at 0 and 150 days. During the experiment Group 1 animals showed improvement in lameness when compared to Group 2 animals. The macroscopic and morphological analysis showed a better tissue repair in the treated horses. Thus, the implantation of autologous PRP showed beneficial effects in the treatment of chondral lesions, experimentally induced in horses.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP