Carcinoma In Wistar Rats Research Articles

A novel quinazoline derivative exhibits potent anticancer cytotoxicity via apoptosis and inhibition of angiogenesis in DMBA-induced mammary gland carcinoma.

Mammary gland carcinoma is one of the most prevalent and deadly diseases among women globally. It is a type of solid malignant tumor. In this malignant tumor, the microenvironment becomes hypoxic in rapidly proliferating cancer cells. These cells undergo adaptive changes through the expression of hypoxia-inducible factor-1alpha (HIF-1α) which is regulated by factor inhibiting HIF-1α (FIH-1). Considering this, we hypothesized that the chemical activation of FIH-1 would inhibit the hypoxic activity of HIF-1α in mammary gland carcinoma. A library of 67,609 chemical compounds was virtually screened against FIH-1 based on Lipinski's rule from the ZINC database. The BBAP-8 has been selected based on an excellent docking score (-8.352 Kcal/mol), favorable ADMET, and potential FIH-1 activator profile. Further, its in-vitro cytotoxicity and apoptotic activity were scrutinized against MCF-7 cells and in-vivo activity against 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary gland carcinoma in Wistar rats. It exhibited significant cytotoxicity (IC50 = 16.59 ± 0.49 μM) and activated apoptosis when scrutinized through DAPI, AO/EB, and JC-1 staining. Also, oral administration of BBAP-8 restored hemodynamic changes, normalized tissue architecture, and corrected metabolic abnormalities. The western blot analysis and mRNA expression analysis validated that BBAP-8 has the potential to activate FIH-1 with the downregulation of GLUT-1, VEGF, and Twist-1. Moreover, BBAP-8 fostered apoptosis, when evaluated through BCL-2, BAX, Caspase-8, and Caspase-3. Based on research findings, this implies that BBAP-8 activates FIH-1 and can be effective in chemotherapeutic treatment of mammary gland carcinoma.

Chronic Administration of Diethylnitrosamine and 2-Acetylaminofluorene Induces Hepatocellular Carcinoma in Wistar Rats.

This study aimed to analyze the biochemical, histological, and gene expression alterations produced in a hepatocarcinogenesis model induced by the chronic administration of diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) in Wistar rats. Thirteen rats weighing 180 to 200 g were divided into two groups: control and treated. Rats in the treated group were administered an intraperitoneal (i.p.) injection of DEN (50 mg/kg/week) and an intragastric (i.g.) dose of 2-AAF (25 mg/kg/week) for 18 weeks. The treated group had significant increases in their total cholesterol, HDL-C, AST, ALT, ALKP, and GGT levels. Furthermore, a histological analysis showed the loss of normal liver architecture with nuclear pleomorphism in the hepatocytes, atypical mitosis, and fibrous septa that were distributed between the portal triads and collagen fibers through the hepatic sinusoids. The gene expressions of 24 genes related to fibrosis, inflammation, apoptosis, cell growth, angiogenesis, lipid metabolism, and alpha-fetoprotein (AFP) were analyzed; only TGFβ, COL1α1, CYP2E1, CAT, SOD, IL6, TNF-α, and ALB showed significant differences when both groups were compared. Additionally, lung histopathological alterations were found in the treated group, suggesting metastasis. In this model, the chronic administration of DEN+2-AAF induces characteristic alterations of hepatocellular carcinoma in Wistar rats without AFP gene expression changes, highlighting different signatures in hepatocellular carcinoma heterogeneity.

Detection and Isolation of Aflatoxin-producing Aspergillus sp. in Chewing and Smokeless Tobacco by Microbial and Molecular Detection Methods and Its Influence on Hepatocellular Carcinomas in Wistar Rats

Detection and Isolation of Aflatoxin-producing Aspergillus sp. in Chewing and Smokeless Tobacco by Microbial and Molecular Detection Methods and Its Influence on Hepatocellular Carcinomas in Wistar Rats

Protective Effects of Naringin-Dextrin Nanoformula against Chemically Induced Hepatocellular Carcinoma in Wistar Rats: Roles of Oxidative Stress, Inflammation, Cell Apoptosis, and Proliferation.

Nanotechnology holds great promise for the development of treatments for deadly human diseases, such as hepatocellular carcinoma (HCC). In the current study, we compared the hepatoprotective effects of naringin-dextrin nanoparticles (NDNPs) against HCC in male Wistar rats with those of pure naringin and investigated the underlying cellular and molecular mechanisms. HCC was induced by intraperitoneal injection of diethylnitrosamine (DEN, 150 mg/kg body weight (b.w.) per week) for two weeks, followed by oral administration of 2-acetylaminofluorene (2AAF, 20 mg/kg b.w.) four times per week for three weeks. DEN/2AAF-administered rats were divided into three groups that respectively received 1% carboxymethyl cellulose (as vehicle), 10 mg/kg b.w. naringin, or 10 mg/kg b.w. NDNP every other day by oral gavage for 24 weeks. Both naringin and NDNP significantly attenuated the harmful effects of DEN on liver function. Both compounds also suppressed tumorigenesis as indicated by the reduced serum concentrations of liver tumor markers, and this antitumor effect was confirmed by histopathological evaluation. Additionally, naringin and NDNP prevented DEN-induced changes in hepatic oxidative stress and antioxidant activities. In addition, naringin and NDNP suppressed inflammation induced by DEN. Moreover, naringin and NDNP significantly reduced the hepatic expression of Bcl-2 and increased Bax, p53, and PDCD5 expressions. Naringin and NDNP also reduced expression of IQGAP1, IQGAP3, Ras signaling, and Ki-67 while increasing expression of IQGAP2. Notably, NDNP more effectively mitigated oxidative stress and inflammatory signaling than free naringin and demonstrated improved antitumor efficacy, suggesting that this nanoformulation improves bioavailability within nascent tumor sites.

Diethylnitrosamine and 2-acetylaminofluorene chronic administration leads to biochemical and histologic changes related to hepatocellular carcinoma in Wistar rats

Diethylnitrosamine and 2-acetylaminofluorene chronic administration leads to biochemical and histologic changes related to hepatocellular carcinoma in Wistar rats

Polysaccharide-Rich Fractions from Ganoderma resinaceum (Ganodermataceae) as Chemopreventive Agents in N-Diethylnitrosamine-Induced Hepatocellular Carcinoma in Wistar Rats.

Hepatocellular carcinoma (HCC) is one of the most common and lethal diseases worldwide. Its treatment remains ineffective and the prognosis remains severe, thus favoring the emergence of a preventive approach. Mushroom-derived polysaccharides offer great opportunities because of their less toxicity and bioactivities. The present study aimed to investigate the chemopreventive effects of water-soluble polysaccharides from Ganoderma resinaceum on HCC. Two G. resinaceum polysaccharide-rich fractions (GRP I and GRP II) were obtained following hot water and alcohol precipitation. Their proteins, phenol compounds, and total neutral sugar content were assayed. The in vitro antiproliferative effect was assessed in MDA-MB 231, Hela, and HepG2 using the MTT assay. Further, for the in vivo study, seven groups of nine rats each received N-diethylnitrosamine (100 mg/kg BW), vehicle (NaCl 0.9%), doxorubicin (10 mg/kg BW), or G. resinaceum polysaccharides (125 and 250 mg/kg BW). Liver cancer initiation and progression was assessed by evaluating histomorphology of liver section, hepatic injury markers, hematology, cytokines/chemokines levels, and stress oxidative markers. GRP II presented higher protein and sugar and lower phenol compound content than GRP I. GRP exhibited CC50 of 340 and 261.7 in HepG2 cells after 48 h. Moreover, GRP I and GRP II (125 and 250 mg/kg) prevented the alteration of the histoarchitecture of the liver induced by the DEN. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-fetoprotein (AFP), proinflammatory cytokines (G-CSF, IFNγ, and TNFα), and chemokines (eotaxin and fractalkine) levels were significantly decreased in the GRP I- and GRP II-treated groups, while anti-inflammatory cytokines (IL-10 and IL-12p70) levels were increased. The antioxidant defense was also stimulated by reducing malondialdehyde (MDA) and nitric oxide (NO2) levels, increasing catalase (CAT) and superoxide dismutase (SOD) activities, and reducing glutathione (GSH) levels. Our results indicate that GRP I exhibits chemopreventive effects by inhibiting cell proliferation and restoring liver architecture, antioxidant enzymes, and cytokines/chemokines balance.

The modulatory effect of bee honey against diethyl nitrosamine and carbon tetrachloride instigated hepatocellular carcinoma in Wistar rats.

The current study confirmed that honey has the potential to act as an antimetastatic factor. Bee honey supplementation either before or after combined injection of DEN/CCl4 exhibited inhibitory and ameliorative effects against DEN/CCl4-induced HCC through its antioxidant, antiproliferative, anti-metastatic, antifibrotic, and apoptosis properties. To our knowledge, this is the first study to describe the molecular mechanisms underlying honey's effects against DEN/CCl4-induced HCC in rats.

Camel (Camelus Dromedarius) Milk Antibodies Ameliorated Diethylnitrosamine-Induced Hepatocellular Carcinoma in Wistar Rats

Hepatocellular carcinoma (HCC) is an extremely aggressive solid tumor and relates to numerous cases of cancer-associated deaths globally. Current studies reveal that natural compounds retain various therapeutic effects. This study was aimed to investigate the beneficial antitumor effects of camel (Camelus dromedarius) milk antibodies (CM-IgG) on diethylnitrosamine (DENA)-induced hepatocellular carcinoma in male Wistar rats. Hepatocarcinoma was induced in rats using DENA (50 mg/kg, twice/week) for 2 weeks followed by CCl4 (1 ml/kg, trice/week) for 6 weeks. At week 17th, HCC-bearing rats were orally administrated CM-IgG (100 mg/kg, orally) daily for 4 weeks. Liver enzyme activities and levels of alpha-fetoprotein (AFP) were measured in serum. Lipid peroxidation, nitric oxide, reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity were determined in liver homogenate. Histological analysis using hematoxylin and eosin stain was examined in liver tissues. Hepatic mRNA gene expression of placental glutathione-s-transferase (GST-P) was determined by qRT-PCR. Treatment HCC-bearing rats with CM-IgG significantly reduced liver injury biomarkers and attenuated oxidative stress as well as enhanced antioxidant status. Moreover, CM-IgG significantly alleviated hepatocellular morphology alterations and down-regulated GST-P gene expression levels in liver. Our results revealed the potential role of total immunoglobulin IgG purified from camel milk in amelioration of DENA-induced hepatocellular dysfunction and oxidative stress in hepatocarcinoma-bearing rats.

VEGFR-2 kinase domain inhibition as a scaffold for anti-angiogenesis: Validation of the anti-angiogenic effects of carotenoids from Spondias mombin in DMBA model of breast carcinoma in Wistar rats.

Vascular endothelial growth factor (VEGF) and its receptor-2 (VEGFR-2) mediated tumorigenesis, metastasis, and angiogenesis are the cause of the increased levels of mortality associated with breast cancer and other forms of cancer. Inhibition of VEGF and VEGFR-2 provides a great therapeutic option in the management of cancer. This study employed VEGFR-2 kinase domain inhibition as an anti-angiogenic scaffold and further validate the anti-angiogenic effects of the lead phytochemicals, carotenoids from Spondias mombin in 7, 12-Dimethylbenz[a]anthracene (DMBA) model of breast carcinoma in Wistar rats. Phytochemicals characterized from 6 reported anti-cancer plants were screened against the VEGFR-2 kinase domain. The lead phytochemicals, carotenoids from Spondias mombin were isolated and subjected to Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (LC-ESI-MS) for characterization. The anti-angiogenic potentials of the carotenoid isolates were validated in the DMBA model of breast carcinoma in female Wistar rats through assessment of the expression of anti-angiogenic related mRNAs, histopathological analysis, and molecular docking. Treatment with carotenoid isolates (100 mg/kg and 200 mg/kg) significantly (p < 0.05) downregulated the expression of VEGF, VEGFR, Epidermal Growth Factor Receptor (EGFR), Hypoxia-Inducible Factor-1(HIF-1), and Matrix Metalloproteinase-2 (MMP-2) mRNAs in the mammary tumours, while the expression of Chromodomain Helicase DNA-Binding Protein-1 (CHD-1) mRNA was significantly (p < 0.05) upregulated. DMBA induced comedo and invasive ductal subtypes of breast carcinoma. The binding of astaxanthin, 7,7',8,8'-tetrahydro-β,β-carotene, and beta-carotene-15,15'-epoxide to the ATP binding site led to the DFG-out conformation with binding energies of -8.2 kcal/mol, -10.3 kcal/mol, and -10.5 kcal/mol respectively. Carotenoid isolates demonstrated anti-angiogenic and anti-proliferating potentials via VEGFR-2 kinase domain inhibition.

Anti-cancer Effects of Azadirachta indica in Diethylnitrosamine-Induced Hepatocellular Carcinoma in Wistar Rats

Hepatocellular carcinoma (HCC) is a primary liver cancer and has a high rate of mortality. Exploration of local herbal as a chemo-preventive drug has been conducted. This present study aimed to observe the anti-cancer effect of hydroethanolic extracts of Azadirachta indica both Indonesia (HEAII) and the Philippines (HEAIP) on diethylnitrosamine (DEN)-induced HCC on Wistar rat model. VEGF/FGF2/CD166/YAP were evaluated using immunohistochemistry. VEGF/FGF2/CD166/YAP were down-regulated in HCC treated with HEAII and HEAIP compare to that non-treatment HCC. Liver function (aminotransferase (AST) and aminotransferase (ALT) activities) was evaluated from serum. Value of AST and ALT were abnormal in the non-treatment HCC and normal in the HCC treated. These results indicated that both extracts were found to possess anti-cancer activity in HCC.

Fisetin suppresses 1,2-dimethylhydrazine-induced colon tumorigenesis in Wistar rats via enhancing the apoptotic signaling pathway

The present research exploration is intended to inspect the chemotherapeutic potency of fisetin in 1,2‑dimethylhydrazine (DMH)-stimulated colon carcinoma in Wistar rats. The 20 mg/kgb·wt of DMH was injected to the investigational rats via subcutaneous route once in a week for 15 weeks to induce colon cancer in a rat model. Fisetin at 50 mg/kgb·wt dose were administered throughout the experimental period. Biochemical methods were employed to study the antioxidant, lipid peroxidation, Phase-I & II enzymes. Pro-inflammatory cytokines and apoptotic proteins were measured using Elisa methods. Colon tissue damages were examined using hematoxylin and eosin staining. Our result suggested that fisetin treatment efficiently decreased the tumor incidence andnumber by restoring the antioxidant status, phase-II enzymes and inhibiting the actions of phase-I enzymes and lipid peroxidative events in DMH-induced colon tumorigenesis model. Further, we noticed that fisetin treatment significantly inhibited the pro-inflammatory cytokine production. Moreover, we observed that fisetin treatment remarkably inhibited the anti-apoptotic Bcl-2 and induced pro-apoptotic Caspase-9 and Caspase-3 expression, thereby induces apoptosis in DMH-induced colon tumorigenesis model. From this observation, we conclude that fisetin (50 mg/kgb·wt) can efficiently prevent chemically induced colon cancer by enhancing antioxidant status and modulating inflammatory and apoptotic signalling events.

Chemoprotective Effects of Resveratrol Against Diethylnitrosamine Induced Hepatocellular Carcinoma in Wistar Rats

Chemoprotective Effects of Resveratrol Against Diethylnitrosamine Induced Hepatocellular Carcinoma in Wistar Rats

Antineoplastic influence of nimesulide in chemically induced hepatocellular carcinoma by inhibition of DNA synthesis

Hepatocellular carcinoma is emerging as one of the most common forms of cancer resulting in thousands of death worldwide. The purpose of this study was to screen nimesulide for anticancer activity in chemically induced hepatocellular carcinoma in Wistar rats as well as in BEL 7402 and HEP G2 cell lines. HCC in rats was induced by administering a single dose of diethyl nitrosamine (150mg/kg) intraperitoneally. Duration of the in vivo study was 12weeks and the anticancer potential was further confirmed by in vitro cell line study. Administration of DENA in Wistar rats significantly elevated the levels of serum biochemical parameters and α-feto protein. Treatment with different dose of nimesulide significantly decreased the markedly raised serum levels of biochemical parameters as well as maintained the histology of the liver tissues nearly similar to the normal. Further study of hepatocytes enzymes showed that treatment with nimesulide also improved the antioxidant enzyme levels. Our study also examined the cytotoxicity and DNA synthesis inhibition by nimesulide in BEL 7402 and Hep G2 cell lines. Cell viability was assessed by [3H]-thymidine uptake procedure. The results obtained by in vitro cell line study, histopathological and biochemical data concluded that nimesulide, a preferential COX-2 inhibitor, has anticancer activity, which is by first reducing the formation of reactive oxygen species and second by inhibiting the PGE2 effect via Wnt signaling pathway (cell invasion, angiogenesis, and cell proliferation).

Immunohistochemical, histopathological study and chemoprotective effect of Solanum nigrum in N-nitrosodiethylamine-induced hepatocellular carcinoma in Wistar rats.

Background and AimCancer is a devastating disease with a severe impact on the physical and psychological well-being of patients. Hepatocellular carcinoma (HCC) has been reported in various species of animals including dogs, cats, sheep, and pigs. The present study aimed to study the immunohistochemical and histopathological changes andchemoprotective effect of aqueous and alcoholic extracts of Solanum nigrum on N-nitrosodiethylamine (NDEA)-induced HCC rat model.Materials and MethodsEighty-two male Wistar rats of 15 weeks of age weighing 200-250 g were selected for the experiment. They were randomly divided into ten groups. Group I served as normal control consisted of healthy rats. HCC was induced in Group II, IV, V, VI, VII, and X rats using NDEA as inducing agent followed by phenobarbitone as a promoter for 16 weeks. Group II rats were kept untreated as HCC control. Group III rats were kept as vehicle control (0.05% Sodium bicarbonate). Group IV and V rats were treated with aqueous extract of S. nigrum at 200 mg/kg and 400 mg/kg, respectively, and Group VI and VII rats were treated with an alcoholic extract of S. nigrum at 200 mg/kg and 400 mg/kg, respectively, daily orally for 28 days. Group X rats were treated withsorafenib as reference drug at a dose of 11.4 mg/kg daily orally for 28 days. Group VIII and IX rats were kept as aqueous and alcoholic extract control for studying the effect of the same on normal rats. Liver samples were collected to study the gross and histopathological lesions and the activity of cleaved caspase-3 and chemopreventive effect of aqueous and alcoholic extracts of S. nigrum on HCC.ResultsThe liver sections of rats from HCC control (Group II) showed loss of lobular architecture, necrosis, fatty change, enlarged and darkened nuclei with variable size, dilatation of hepatic sinusoids with Kupffer cell hyperplasia, dilatation and proliferation of bile duct, and intranuclear vacuoles and also showed the presence of more than one nucleolus. Administration of alcoholic extract of S. nigrum and sorafenib to NDEA/phenobarbital-treated rats reduced the severity of lesions in the liver. Immunohistochemical analysis of liver sections for caspase-3-positive cells of hepatic cancer-induced group showed immunoreactivity to rarely few. The immunoreactivity of the hepatocytes treated with a higher dose of alcoholic extract of S. nigrum was limited and was comparable to a standard drug, sorafenib.ConclusionOral administration of aqueous and alcoholic extracts of S. nigrum for 28 days showed significant rejuvenation in the structure of the liver in the histopathological section in a dose-dependent manner in rats.

Evaluation of Chemoprotective Effect of Quercetin from Argyreia speciosa against N-methyl-N-Nitro-N-Nitrosoguanidine and NaCl-Induced Gastric Carcinomas in Wistar Rats

Evaluation of Chemoprotective Effect of Quercetin from Argyreia speciosa against N-methyl-N-Nitro-N-Nitrosoguanidine and NaCl-Induced Gastric Carcinomas in Wistar Rats

Chemo Preventive Effect of Rutin Against N-Nitrosodiethylamine-Induced and Phenobarbital- Promoted Hepatocellular Carcinoma in Wistar Rats

Chemo Preventive Effect of Rutin Against N-Nitrosodiethylamine-Induced and Phenobarbital- Promoted Hepatocellular Carcinoma in Wistar Rats

Anti-cancer effects of Ajwa dates (Phoenix dactylifera L.) in diethylnitrosamine induced hepatocellular carcinoma in Wistar rats

BackgroundHepatocellular carcinoma (HCC) accounts for major cancer-related deaths despite current advanced therapies. Treatment and prognosis of HCC is better in patients with preserved liver function. Many natural products including ajwa dates (Phoenix dactylifera L.), are claimed to have hepatoprotective and HCC inhibitory effects, but most lack scientific validation. To prove our hypothesis, we attempted to evaluate the HCC inhibitory effects, and other beneficial properties of the aqueous extract of ajwa dates (ADE) in a rat model of diethylnitrosamine (DEN) induced liver cancer.MethodsThirty-two male rats were divided into four groups of eight each as follows, Group A: untreated control; Group B: DEN control (180 mg/kg bw), Group C: DEN + ADE 0.5 g/kg bw; and Group D: DEN +1.0 g/kg bw. Rats from all groups were assessed for liver cancer progression or inhibition by evaluating histological, biochemical, antioxidant enzyme status, cytokines and gene expression profiles.ResultsDEN treatment Groups (B, C, D) showed histological features of HCC and in rats treated with ADE (Groups C, D) partial to complete reversal of normal liver architecture was observed. Antioxidant enzymes such as superoxide dismutase (SOD), glutathione reductase (GR), glutatione peroxidase (GPx) and catalase (CAT) were increased, while the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels and lipid peroxidation were significantly decreased in Group C and Group D compared to Group B. Pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1β,, GM-CSF) were increased in the serum of rats in Group B while the anti-tumor cytokines (IL-2, IL-12) were increased in ADE treated Groups (C, D). In addition, Alpha-Feto Protein (AFP) and IL-6 gene expression levels were upregulated in Group B, while they were significantly downregulated in ADE treated Groups (C, D).ConclusionsADE helped in the reversal of DEN damaged liver towards normal. Restoration of anti-oxidant enzymes, liver enzymes, cytokines balance and gene expression to normal levels following ADE treatment indicates that ADE improves liver function and inhibits HCC. ADE can, therefore, be used together with conventional therapeutics for HCC.

In vitro and in vivo anticancer studies of 2'-hydroxy chalcone derivatives exhibit apoptosis in colon cancer cells by HDAC inhibition and cell cycle arrest.

Considering the therapeutic values of bioflavonoids in colon cancer treatment, six 2ʹ-hydroxy chalcones (C1-C6) were synthesized, characterized and screened for in vitro cytotoxicity on human colon carcinoma (HCT116) and African green monkey kidney epithelial cells (Vero). Only C5 showed selective cytotoxicity against HCT116 cells. Other potent cytotoxic compounds were C1, C2 and C3. Further screening included enzyme inhibition studies on histone deacetylase (HDAC) enzyme where C1 showed lowest IC50 value (105.03 µM). Based on cytotoxicity data C1, C2 and C3 were selected for further in vitro mechanistic studies, namely apoptotic studies (Acridine orange/Ethidium bromide (AO/EB) and Annexin V), cell cycle analysis using propidium iodide (PI) stain and in vivo anticancer efficacy in 1,2-dimethyl hydrazine (DMH) induced colorectal carcinoma in Wistar rats. The compounds induced apoptosis in more than 30 % cells in AO/EB and Annexin V staining. They also showed cell cycle arrest in G2/M phase with PI staining. They showed a significant reduction in aberrant crypt foci formation and adenocarcinoma count along with a significant (p<0.05) reduction in TNF-α levels as compared to DMH control at 100 mg/kg dose. Thus, it can be concluded that the synthesized 2ʹ-hydroxychalcones were effective against colon adenocarcinoma in in vitro and in vivo studies.

Correlation of AgNOR count with biological behavior of N-Nitroso-N-Methylurea (NMU)-induced squamous cell carcinoma in Wistar rats

Gastric squamous cell carcinoma is one of the most common malignancies in human beings throughout the world. Assessment of proliferative aggressiveness of squamous cell carcinoma plays an important role in diagnostic, prognostic and therapeutic decisions on them. It is determined by both proliferative fraction and speed of neoplastic cells. AgNOR count is an important easily feasible histochemical technique to assess both proliferative fraction and speed of tumour growth. The present study was aimed at evaluating the ability of AgNOR count to assess proliferative speed of a tumour by correlating with pathomorphological parameters of tumour growths (grading, tumour volume, multinodularity, total number of neoplastic cells and survival period) induced in seven Wistar rats by intraperitoneal administration of N-Nitroso-N-Methylurea (NMU) at the dose rate of 50mg/kg b.wt. once per week for four weeks. Tumours were harvested on necropsy after the natural death of experimental rats. Out of total seven cases of gastric squamous cell carcinoma, four tumours were grade II and other three were of grade III. The t-test showed significantly higher mean values of mAgNOR count, mitotic figure count and different pathomorphological parameters of biological behavior i.e., tumour volume, multinodularity and total cell count in Grade-III compared to Grade-II gastric squamous cell carcinomas, indicating their biologically more aggressive growth. It was observed that mAgNOR count may be helpful in predicting real proliferative nature of a tumour and may help in taking diagnostic, prognostic and therapeutic decisions on gastric squamous cell carcinomas.

Establishment of experimental implantation tumor models of hepatocellular carcinoma in Wistar rats

Our aims were to investigate and establish simple and reliable implanted hepatocellular carcinoma (HCC) models in Wistar rats. Concentrated suspensions of CBRH-7919 cancer cell lines were injected subcutaneously into the scapular regions of nude mice. The developing tumor tissues were then implanted into the livers of 45 adult Wistar rats. Dexamethasone (2.5 mg/day) was injected intramuscularly daily for 1 week preoperatively and 2 weeks postoperatively. After 4 weeks of implantation, ultrasonography and nuclear magnetic resonance imaging (MRI) were performed to identify model rats with liver tumor growth and to analyze the growth and characteristics of the tumors. Five of these model rats were then sacrificed, and the tumors were removed from the liver for pathological examination. Three rats died during the operation; among the remaining 42 rats, 36 possessed a total of 43 liver tumors. The success rate of tumor implantation was 85.7 % (36/42), and the diameters of the tumors ranged from 5 to 10 mm. All tumor specimens were confirmed to be HCC by pathological examination. This study provides a new approach for establishing implanted HCC models in Wistar rats, which can be used for studying numerous biological features of HCC.