The Experts below are selected from a list of 162 Experts worldwide ranked by ideXlab platform
Hiroyuki Tsuda - One of the best experts on this subject based on the ideXlab platform.
-
potential preventive effects of chelidonium majis l papaveraceae herb extract on glandular Stomach Tumor development in rats treated with n methyl n nitro n nitrosoguanidine mnng and hypertonic sodium chloride
Cancer Letters, 1997Co-Authors: Hiroyuki TsudaAbstract:The modifying effects of Chelidonium majis L. (Papaveraceae) herb extract (CH), an analgesic traditionally prescribed for gastric and duodenal ulcer patients, on gastric Tumor development were studied in rats given N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). Sixty-four male 6-week-old Wistar rats were used. Group 1 rats were initially given MNNG (200 mg/kg b.w.) by gavage at days 0 and 14 as well as saturated sodium chloride solution (S-NaCl, 1 ml per rat) every 3 days during weeks 0–3 (six times), and then placed on basal diet containing 0.1 or 0.2% CH for 16 weeks from week 4. Rats of Groups 2 and 3 were treated with MNNG together with S-NaCl or saline (0.9% NaCl, 1 ml per rat), respectively, timed as in Group 1 but without further treatment. All surviving animals were killed at week 20 and histopathologically investigated. In the glandular Stomach, the number of preneoplastic pepsinogen 1 altered pyloric glands (PAPGs) in the MNNG + S-NaCl → CH (0.1%) group (Group 1) was significantly smaller than in the MNNG + S-NaCl group (Group 2) (P < 0.02). The incidences of foreStomach neoplastic lesions (papillomas and squamous cell carcinomas) also showed a tendency to decrease with the CH treatment. The results thus indicate that CH exerts inhibitory effects on glandular Stomach carcinogenesis in the rat, so that it may have potential as a chemopreventive agent for Stomach cancer in man.
-
Immunohistochemical Demonstration of Intestinal‐type Alkaline Phosphatase in Stomach Tumors Induced by N‐Methyl‐N′‐nitro‐N‐nitrosoguanidine in Rats
Japanese Journal of Cancer Research, 1994Co-Authors: Hirofumi Yuasa, Kazuyuki Hirano, Hirohiko Kodama, Hayao Nakanishi, Toshio Imai, Hiroyuki Tsuda, Katsumi Imaida, Masae TatematsuAbstract:: A polyclonal antibody against rat intestinal-type alkaline phosphatase (I-ALP) was generated and proven to be applicable immunohistochemically to paraffin-embedded sections. Expression of I-ALP in normal tissues, intestinal metaplasia and Stomach Tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was then investigated in five different strains of rats. Male SD (Crj:CD), Lewis (LEW/Crj), WKY (WKY/NCrj), Wistar (Crj:Wistar) and F344 (F344/DuCrj) animals were given drinking water containing 100 micrograms/ml of MNNG for 30 weeks and were killed at week 50. Among the 5 strains, Stomach adenocarcinomas were found most frequently in the SD case. The susceptibility of rats to induction of Stomach carcinoma did not correlate with the development of intestinal metaplasias in each strain. Histochemical staining for mucin demonstrated all Stomach Tumors (adenomatous hyperplasias and well-differentiated adenocarcinomas) to consist mainly of gastric type cells (pyloric gland cell and surface mucous cell types), with intestinal-type Tumor cells (goblet cell and intestinal absorptive cell types) being only occasional findings. Immunohistochemically, I-ALP was strongly positive on the striated cell borders of small intestinal absorptive cells of the villus and on brush borders of epithelial cells of kidney proximal tubules. I-ALP was also detected in the normal Stomach, limited to the striated cell borders of absorptive cells of the upper one-fourth of intestinal metaplastic glands. I-ALP may thus be a useful marker for Stomach Tumor cells of intestinal absorptive cell type, indicative of maturation and differentiation. No Stomach Tumors consisting mainly of intestinal-type cells were found, and therefore there was no suggestion of any derivation from intestinal metaplasias.
Chie Furihata - One of the best experts on this subject based on the ideXlab platform.
-
Appearance of osteonectin-expressing fibroblastic cells in early rat Stomach carcinogenesis and Stomach Tumors induced with N-methyl-N'-nitro-N-nitrosoguanidine.
Japanese Journal of Cancer Research, 2020Co-Authors: Hack-young Maeng, Dong-kug Choi, Motoi Takeuchi, Masami Yamamoto, Michiyo Tominaga, Tetsuya Tsukamoto, Masae Tatematsu, Yoshiyuki Sakaki, Chie FurihataAbstract:: The present study was designed to define molecular alterations in the initiation stage of rat Stomach carcinogenesis. Groups of male Lewis rats, 6 weeks old, were given drinking water with or without N-methyl-N'-nitro-N-nitrosoguanidine (MNNG; 100 mg/liter). Total RNA was isolated from the Stomach pyloric mucosa, and fluorescent differential display analysis was performed. A cDNA fragment of 125 bp encoding an extracellular matrix-associated matricellular glycoprotein, osteonectin, was identified after 14 days of MNNG exposure. A severalfold increase in expression was observed after 14 and 27 days of MNNG exposure, as determined by northern blot and RT-PCR. Immunohistochemistry revealed that osteonectin-mAb-stained fibroblastic cells appeared in interstitial tissue of pyloric mucosa. Additionally the gene expression of other extracellular matrix proteins, viz., collagen type III, fibronectin, osteopontin, proteoglycan NG2, laminin gamma1 and S-laminin, was also markedly increased, as determined by competitive RT-PCR after 14 days of MNNG exposure. The gene expression of osteonectin and the six other extracellular matrix proteins was elevated in twelve Stomach adenocarcinomas and adenomas induced by MNNG in Lewis and WKY rats. Osteonectin-mAb-stained fibroblastic cells were evident in interstitial tissue of Stomach Tumor. These results suggest that osteonectin-expressing fibroblastic cells appear in the interstitial tissue of pyloric mucosa from the early initiation stage of rat Stomach chemical carcinogenesis, and that this phenomenon probably plays a role in cancer development.
-
Cause and effect between concentration-dependent tissue damage and temporary cell proliferation in rat Stomach mucosa by NaCl, a Stomach Tumor promoter
Carcinogenesis, 1996Co-Authors: Chie Furihata, Hiroyoshi Ohta, Tsutomu KatsuyamaAbstract:: This study was designed to test whether concentration or dose of NaCl was responsible for the initial tissue damage (after 1 min) and resulting temporary cell proliferation at 17 h in Stomach mucosa of male F344 rats after gastric intubation of 0.65, 1.3, 2.6 and 3.7 M NaCl. Histological damage was studied by dual staining combining horseradish peroxidase-labeled Griffonia simplicifolia agglutinin-II staining (HRP-GSA-II) and periodic acid cold thionin-Schiff reaction (PATS). Cell proliferation was studied by measuring replicative DNA synthesis with liquid scintillation counting and by BrdU staining. NaCl at the same overall dose of 0.8 g/kg body weight induced different degrees of response depending on the concentration. For 4 ml of 0.65 M NaCl, there was no tissue damage after 1 min nor any increase in replicative DNA synthesis after 17 h in the pyloric mucosa. Administration of 1.3 M NaCl (2 ml), 2.6 M NaCl (1 ml) and 3.7 M NaCl (0.7 ml) induced concentration-dependent damage of the surface mucous cell layer after 1 min and increased replicative DNA synthesis after 17 h (P
-
In vivo short-term assays for Tumor initiation and promotion in the glandular Stomach of Fischer rats.
Mutation Research\ reviews in Genetic Toxicology, 1995Co-Authors: Chie Furihata, Taijiro MatsushimaAbstract:Abstract Here we summarize the data on 55 compounds tested in in vivo short-term assays for Tumor-initiating and Tumor-promoting activity in the glandular Stomach of male Fischer (F344) rats. Most of the data has been previously published. Tumor-initiating activity was assayed by measuring the induction of unscheduled DNA synthesis (UDS) and DNA single strand scission; Tumor-promoting activity was assayed by measuring the induction of ornithine decarboxylase (ODC) activity, increased replicative DNA synthesis (RDS), and of c- fos and c- myc oncogene expression. The compounds were orally administered. Twenty-nine compounds were tested for UDS. Eight were positive, including 5 glandular Stomach carcinogens; 16 were negative, including 5 liver carcinogens; and 5 were equivocal. Twenty compounds were tested for DNA single strand scission. Twelve were positive, including 6 glandular Stomach carcinogens; 7 negative, including 2 liver carcinogens; and 1 was equivocal. Thirty-two compounds were tested for RDS. Twenty-six were positive, including 8 glandular Stomach carcinogens and 6 glandular Stomach Tumor-promoters; 4 were negative, including 3 liver carcinogens and a Stomach irritant; and 2 were equivocal. Forty-five compounds were tested for ODC. Thirty-seven were positive, including 8 glandular Stomach carcinogens and 6 glandular Stomach Tumor promoters; 7 were negative, including 3 liver carcinogens; and one was equivocal. All glandular Stomach carcinogens and Tumor-promoters examined were positive in both RDS and ODC. Two compounds were tested for c- fos and c- myc expression; one was a glandular Stomach carcinogen and one was a glandular Stomach Tumor promoter, and both were positive. In addition, 2 compounds inhibited the increase in RDS induced by the Tumor promoter NaCl, suggesting anti-Tumor-promoter activity. Thus these assays are useful for assessing potential Tumor-initiating and Tumor-promoting activity in the rat glandular Stomach.
George S. Bailey - One of the best experts on this subject based on the ideXlab platform.
-
Protective effect of dietary tomatine against dibenzo[a,l]pyrene (DBP)-induced liver and Stomach Tumors in rainbow trout.
Molecular Nutrition & Food Research, 2007Co-Authors: Mendel Friedman, Jerry D. Hendricks, Tammie J. Mcquistan, Cliff Pereira, George S. BaileyAbstract:The potential anti-carcinogenic effects of tomatine, a mixture of commercial tomato glycoalkaloids a-tomatine and dehydrotomatine (10:1), were examined in the rainbow trout chemoprevention model. Prior to the chemoprevention study, a preliminary toxicity study revealed that tomatine in the diet fed daily at doses from 100 to 2000 parts per million (ppm) for 4 weeks was not toxic to trout. For the Tumor study, replicate groups of 105 trout were fed diets containing dibenzo[a,l]pyrene (DBP) alone (224 ppm), (N = 3), DBP plus tomatine at 2000 ppm (N = 2), tomatine alone (N = 2), or control diet (N = 2) for 4 weeks. The fish were then returned to control diet for 8 months and necropsied for histopathology. Dietary tomatine was found to reduce DBP-initiated liver Tumor incidence from 37.0 to 19.0% and Stomach Tumor incidence from 46.4 to 29.4%. Tomatine also reduced Stomach Tumor multiplicity. The tomatine-containing diets did not induce mortality, change in fish weights, or liver weights. No adverse pathological effects in the tissues of the fish on the tomatine diets were observed. Dose-response and chemopreventive mechanisms for tomatine protection remain to be examined. This is the first report on the anticarcinogenic effects of tomatine in vivo.
-
Organ specific, protocol dependent modulation of 7,12-dimethylbenz[a]anthracene carcinogenesis in rainbow trout (Oncorhynchus mykiss) by dietary ellagic acid
Carcinogenesis, 1996Co-Authors: Ulrich Harttig, Jerry D. Hendricks, Gary D. Stoner, George S. BaileyAbstract:This study investigated pre-initiation and post-initiation effects of dietary ellagic acid (EA) on 7,12-dimethyl-benz[a]anthracene (DMBA) multi-organ carcinogenesis in rainbow trout (Oncorhynchus mykiss). EA at 100, 250 (study 2), 1000 and 2000 (study 1) p.p.m. suppressed Stomach adenopapilloma incidence by 33, 60, 70 and 78% (P ≤ 0.001), respectively, as well as Tumor multiplicity (P < 0.01) and size (P < 0.001) when fed continuously following DMBA initiation. However, continuous EA feeding also produced modest (250 p.p.m.) to extensive (1000, 2000 p.p.m.) growth rate suppression in these studies. Retrospective logistic regression modeling of the data allowed separation of growth-related from non-growth-related inhibitory effects. By this approach : (i) Tumor development showed a similarly strong dependence (same regression slope) on animal growth rate in all treatment groups ; (ii) EA-mediated reduction in mean population growth contributed to suppressed Stomach Tumor response above 250 p.p.m. EA ; and (iii) even at high, toxic doses EA displayed inhibitory mechanisms additional to, and distinct from, growth suppression effect. The effects of post-initiation EA were organ specific. Chronic EA treatment significantly suppressed swim-bladder as well as Stomach Tumor incidence at doses ≥ 1000 p.p.m., but increased liver Tumor incidence at doses ≥250 p.p.m. Three protocols examined EA effects on the initiation process. EA fed at 1000 p.p.m. concurrently with 750 p.p.m. dietary DMBA for 7 weeks modestly reduced Stomach Tumor incidence (from 85 to 78%, P < 0.05) and multiplicity (from 6.3 ± 4.3 to 4.9 ± 2.9, P < 0.01), but did not alter swim-bladder or liver response. The effect of EA pretreatment prior to DMBA single-dose initiation by gill uptake was also examined. When fed for 1 week prior to initiation, 2000 p.p.m. EA again imposed a small reduction in Stomach adenoma incidence (from 88 to 78% ; P < 0.05) and multiplicity (from 5.5 ± 3.2 to 4.4 ± 3.2 ; P < 0.01). However, when EA was pre-fed for 3 weeks instead of 1 week, protection in the Stomach was lost and response in liver and swim-bladder significantly increased. In sum, these studies demonstrate that EA influence on DMBA Tumorigenesis in this multi-organ model is highly protocol dependent and organ specific. Post-initiation dietary EA consistently suppressed Stomach Tumor development in trout, at EA doses far lower than those required for protection in rodents. At higher doses, however, EA also displayed toxicity and a potential in some protocols to enhance Tumor response in other organs.
Eiichi Tahara - One of the best experts on this subject based on the ideXlab platform.
-
Effect of epidermal growth factor on rat Stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine.
Pathology International, 2008Co-Authors: Wataru Yasui, Naoki Takekura, Takashi Kameda, Eiichi TaharaAbstract:The effect of epidermal growth factor (EGF) on rat Stomach carcinogenesis induced by N-methyl-N′-nitro-N-nitro-soguanidine (MNNG) was studied. Male Wistar rats given MNNG for 30 weeks in drinking water (80 μg/ml) were treated with S.C. injections of human EGF (10 μg/kg, once daily) at various stages of the carcinogenesis. Four (30.8%) out of 13 rats treated with EGF immediately after cessation of the MNNG treatment had Stomach Tumors including one adenocarcinoma, one adenoma and two carcinoids. No Stomach Tumor was found in rats treated with MNNG alone or in those treated with MNNG and EGF for different periods such as synchronously for 10 weeks, for 30 weeks or throughout the experiment. These findings suggest a possible enhancing effect of EGF on Stomach carcinogenesis in rats. Acta Pathol Jpn 40: 165-171, 1990.
Jerry D. Hendricks - One of the best experts on this subject based on the ideXlab platform.
-
Protective effect of dietary tomatine against dibenzo[a,l]pyrene (DBP)-induced liver and Stomach Tumors in rainbow trout.
Molecular Nutrition & Food Research, 2007Co-Authors: Mendel Friedman, Jerry D. Hendricks, Tammie J. Mcquistan, Cliff Pereira, George S. BaileyAbstract:The potential anti-carcinogenic effects of tomatine, a mixture of commercial tomato glycoalkaloids a-tomatine and dehydrotomatine (10:1), were examined in the rainbow trout chemoprevention model. Prior to the chemoprevention study, a preliminary toxicity study revealed that tomatine in the diet fed daily at doses from 100 to 2000 parts per million (ppm) for 4 weeks was not toxic to trout. For the Tumor study, replicate groups of 105 trout were fed diets containing dibenzo[a,l]pyrene (DBP) alone (224 ppm), (N = 3), DBP plus tomatine at 2000 ppm (N = 2), tomatine alone (N = 2), or control diet (N = 2) for 4 weeks. The fish were then returned to control diet for 8 months and necropsied for histopathology. Dietary tomatine was found to reduce DBP-initiated liver Tumor incidence from 37.0 to 19.0% and Stomach Tumor incidence from 46.4 to 29.4%. Tomatine also reduced Stomach Tumor multiplicity. The tomatine-containing diets did not induce mortality, change in fish weights, or liver weights. No adverse pathological effects in the tissues of the fish on the tomatine diets were observed. Dose-response and chemopreventive mechanisms for tomatine protection remain to be examined. This is the first report on the anticarcinogenic effects of tomatine in vivo.
-
Modulation of 7,12-dimethylbenz[a]anthracene disposition and hepatocarcinogenesis by dieldrin and chlordecone in rainbow trout.
Journal of Toxicology and Environmental Health, 1998Co-Authors: Regina M. Donohoe, Quan Zhang, Lisbeth K. Siddens, Hillary M. Carpenter, Jerry D. Hendricks, Lawrence R. CurtisAbstract:The present study examined whether modified xenobiotic transport, resulting from chlordecone (CD) or dieldrin pretreatment, would alter polycyclic aromatic hydrocarbon (PAH) or organochlorine (OC) target organ doses and subsequent Tumor organo-specificity or incidence rates in rainbow trout. Additionally, the potential for exposure to dieldrin or CD, following PAH exposure, to enhance Tumor incidence was assessed. Evaluation of CD pretreatment effects on [ 14 C]CD disposition in trout was conducted following two ip (0-15 mg/kg) and two dietary (0-0.4 mg/kg/d) pretreatment regimes. To assess the influence of OC pretreatment on cancer induced by the PAH 7,12-dimethyl-benz[a]anthracene (DMBA), juvenile trout were fed control, CD (0.1, 0.4 mg/kg/d), or dieldrin (0.1, 0.3 mg/kg/d) diets for 9 wk, received a waterborne [ 3 H]DMBA exposure (1 mg/L, 20 h), and resumed control, CD, or dieldrin diets for 33 wk. [ 3 H]DMBA disposition and hepatic [ 3 H]DMBA binding were examined immediately and 24 h after exposure. Hepatic and Stomach Tumor incidences were determined 33 wk after DMBA exposure. CD pretreatment did not influence [ 14 ]CD or [ 3 H]DMBA hepatic concentrations, hepatic [ 3 H]DMBA DNA binding, or hepatic/Stomach Tumor incidence. It did, however, elevate bile [ 14 C]CD and [ 3 H]DMBA concentrations. Postinititation exposure to CD weakly enhanced DMBA-induced hepatic Tumor incidence at the low but not the high CD dose. Dieldrin pretreatment did not influence Stomach [ 3 H]DMBA equivalents or Stomach Tumor incidence but did cause an elevation in biliary and hepatic concentrations of [ 3 H]DMBA equivalents. [ 3 H]DMBA binding to liver DNA was significantly increased and hepatic Tumor incidence was elevated by dieldrin pretreatment. Dieldrin treatment following DMBA initiation did not enhance hepatic or Stomach Tumor incidence. Eco-epidemiology studies, to date, have reported correlations between the co-occurrence of PAHs and OCs and elevated Tumor incidence in feral fish, but cause-and-effect relationships have been difficult to establish. The results of the present study confirm that OCs, such as dieldrin and CD, play a role in modifying PA H-induced carcinogenesis in fish.
-
Organ specific, protocol dependent modulation of 7,12-dimethylbenz[a]anthracene carcinogenesis in rainbow trout (Oncorhynchus mykiss) by dietary ellagic acid
Carcinogenesis, 1996Co-Authors: Ulrich Harttig, Jerry D. Hendricks, Gary D. Stoner, George S. BaileyAbstract:This study investigated pre-initiation and post-initiation effects of dietary ellagic acid (EA) on 7,12-dimethyl-benz[a]anthracene (DMBA) multi-organ carcinogenesis in rainbow trout (Oncorhynchus mykiss). EA at 100, 250 (study 2), 1000 and 2000 (study 1) p.p.m. suppressed Stomach adenopapilloma incidence by 33, 60, 70 and 78% (P ≤ 0.001), respectively, as well as Tumor multiplicity (P < 0.01) and size (P < 0.001) when fed continuously following DMBA initiation. However, continuous EA feeding also produced modest (250 p.p.m.) to extensive (1000, 2000 p.p.m.) growth rate suppression in these studies. Retrospective logistic regression modeling of the data allowed separation of growth-related from non-growth-related inhibitory effects. By this approach : (i) Tumor development showed a similarly strong dependence (same regression slope) on animal growth rate in all treatment groups ; (ii) EA-mediated reduction in mean population growth contributed to suppressed Stomach Tumor response above 250 p.p.m. EA ; and (iii) even at high, toxic doses EA displayed inhibitory mechanisms additional to, and distinct from, growth suppression effect. The effects of post-initiation EA were organ specific. Chronic EA treatment significantly suppressed swim-bladder as well as Stomach Tumor incidence at doses ≥ 1000 p.p.m., but increased liver Tumor incidence at doses ≥250 p.p.m. Three protocols examined EA effects on the initiation process. EA fed at 1000 p.p.m. concurrently with 750 p.p.m. dietary DMBA for 7 weeks modestly reduced Stomach Tumor incidence (from 85 to 78%, P < 0.05) and multiplicity (from 6.3 ± 4.3 to 4.9 ± 2.9, P < 0.01), but did not alter swim-bladder or liver response. The effect of EA pretreatment prior to DMBA single-dose initiation by gill uptake was also examined. When fed for 1 week prior to initiation, 2000 p.p.m. EA again imposed a small reduction in Stomach adenoma incidence (from 88 to 78% ; P < 0.05) and multiplicity (from 5.5 ± 3.2 to 4.4 ± 3.2 ; P < 0.01). However, when EA was pre-fed for 3 weeks instead of 1 week, protection in the Stomach was lost and response in liver and swim-bladder significantly increased. In sum, these studies demonstrate that EA influence on DMBA Tumorigenesis in this multi-organ model is highly protocol dependent and organ specific. Post-initiation dietary EA consistently suppressed Stomach Tumor development in trout, at EA doses far lower than those required for protection in rodents. At higher doses, however, EA also displayed toxicity and a potential in some protocols to enhance Tumor response in other organs.