Chemomodulatory Effect of Moringa Oleifera,Lam, on Hepatic Carcinogen Metabolising Enzymes,Antioxidant Parameters and Skin Papillomagenesis in Mice

The modulatory effects of a hydro-alchoholic extract of drumsticks of Moringa oliefera Lam at doses of 125 mg/ ‍kg bodyweight and 250 mg/ kg body weight for 7 and 14 days, respectively, were investigated with reference to drug ‍metabolising Phase I (Cytochrome b5 and Cytochrome P450 ) and Phase II (Glutathione-S- transferase) enzymes, ‍anti-oxidant enzymes, glutathione content and lipid peroxidation in the liver of 6-8 week old female Swiss albino ‍mice. Further, the chemopreventive efficacy of the extract was evaluated in a two stage model of 7,12 – ‍dimethylbenz(a)anthracene induced skin papillomagenesis. Significant increase (p<0.05 to p<0.01) in the activities ‍of hepatic cytochrome b5, cytochrome P450, catalase, glutathione peroxidase ( GPx ), glutathione reductase (GR), acid ‍soluble sulfhydryl content (-SH ) and a significant decrease ( p<0.01 ) in the hepatic MDA level were observed at ‍both dose levels of treatment when compared with the control values. Glutathione-S- transferase ( GST )activity was ‍found to be significantly incr eased (p<0.01 ) only at the higher dose level. Butylated hydr oxyanisol (BHA ) fed at a ‍dose of 0.75% in the diet for 7 and 14 days (positive control ) caused a significant increase (p<0.05 to p<0.01) in the ‍levels of hepatic phase I and phase II enzymes, anti- oxidant enzymes, glutathione content and a decrease in lipid ‍peroxidation. The skin papillomagenesis studies demonstrated a significant decrease (p<0.05 ) in the percentage of ‍mice with papillomas, average number of papillomas per mouse and papillomas per papilloma bearing mouse when ‍the animals received a topical application of the extract at a dose of 5mg/ kg body weight in the peri-initiation phase ‍7 days before and 7 days after DMBA application, Group II ), promotional phase (from the day of croton oil application ‍and continued till the end of the experiment, Group III ) and both peri and post initiation stages (from 7 days prior ‍to DMBA application and continued till the end of the experiment, Group IV) compared to the control group (Group ‍I ). The percentage inhibition of tumor multiplicity has been recorded to be 27, 72, and 81 in Groups II, III, and IV, ‍respectively. These findings are suggestive of a possible chemopreventive potential of Moringa oliefera drumstick ‍extract against chemical carcinogenesis.     

Stability of drug metabolizing enzymes during the incubation conditions of the liver microsomal assay with non-induced and induced mouse liver S-9 fractions

The purpose of this work was to study the relative activitiesand stabilities of phase-I and phase-II drug metabolizing enzymesin incubation mixtures used in in vitro genotoxicity testingin order to optimize the conditions of the assay, increase sensitivityand eliminate false negative results. Cytochrome P-450, NADPH-cytochromeP-450 (cytochrome c) reductase activity and various phase-Iand phase-II enzyme activities of the drug-metabolizing systemwere determined in incubation mixtures used in liver microsomalassays. The behaviour of aminopyrine N-demethylase and p-nitroanisoleO-demethylase activities as phase-I markers have been reportedpreviously. Other activities measured were glutathione S-transferase,glutathione S-epoxide transferase and epoxide hydrase, and lipidperoxidation (LP) was determined. The experiments were carriedout on liver S9 fractions derived from non-induced mice or miceinduced with sodium phenobarbital (PB), and/or ß-naphthoflavone(ß-NF). The phase-II enzymes were much more stable(70–90% residual activity) than phase-I enzyme activities(35–60%) in all conditions tested. The residual cytochromeP-450 was 70% stable and the remaining activity of NADPH-cytochromec-reductase about 80%, indicating that this latter enzyme doesnot limit the rate of the monooxygenase system in these conditions.Phase-II enzymes were induced to a smaller extent (about 2 times)than in phase-I enzymes (5–6 times) by ß-NF+ PB. NADPH-cytochrome c-reductase behaved as phase-II enzymesin this respect as well as for stability. LP was appreciablyhigher in non-induced than in induced animals. Treatment withthe ß-NF + PB mixture, however, showed that inducedenzymes were more stable than those obtained by simple inductionwith either ß-NF or PB alone. These results lead tothe conclusion that prolonged incubation times in mutagenicityassays are unnecessary when considering the relative stabilitiesof the various phase-I and phase-II enzyme activities in thedrug-metabolizing system.     

Anti-tumour,Anti-mutagenic and Chemomodulatory Potentialof Chlorophytum borivilianum

In the present investigation anti-tumour, anti-mutagenic and chemomodulatory potential of Chlorophytumborivilianum were evaluated. Chlorophytum borivilianum root extract had no toxic effect up to a dose of 800 mg/kg body weight/day. Significant increase (p<0.05 to p<0.001) in the activity of reduced glutathione (GSH), catalase(CAT) and superoxide dismutase (SOD) and a significant decrease in the hepatic MDA level were observed at100, 400, and 800 mg/kg body weight of Chlorophytum borivilianum root extract when compared with the controlvalue. Skin papillomagenesis studies demonstrated a significant (p<0.001) decrease in cumulative numbers ofpapilloma, tumour incidence, tumour burden, tumour size and tumour weight and significant (p<0.01) increasein average latent period when the animals received Chlorophytum borivilianum root extract at a dose level of 800mg/kg body weight/day orally in double distilled water at pre, peri and post initiation stages of carcinogenesis. Asignificant reduction in the frequency of chromosomal aberration and micronuclei was observed in the treatedanimals as compared to carcinogen controls. The present investigation suggests that Chlorophytum borivilianumhas anti-tumour, anti-mutagenic and chemomodulatory effects.     

Inhibition of DMBA-croton Oil Two-stage Mouse Skin Carcinogenesis by Diphenylmethyl Selenocyanate Through Modulation of Cutaneous Oxidative Stress and Inhibition of Nitric Oxide Production

Selenium, an essential micronutrient, plays important roles against different diseases, including several types of ‍cancer. In the present study, antioxidative and chemopreventive properties of a synthetic organoselenium compound, ‍diphenylmethyl selenocyanate, were evaluated with a 7,12-dimethylbenz (a) anthracene - croton oil induced twostage ‍mouse skin carcinogenesis model. ‍The compound was administered orally to carcinogen-treated mice at two different non-toxic doses, 2mg/kg. ‍b.w. and 3mg/kg. b.w. Significant inhibition in the incidence of papilloma formation (53-80%) as well as in the ‍cumulative numbers of papillomas per papilloma bearing mouse were observed in the treated groups as compared ‍to the carcinogen control group. The compound was also found to upregulate significantly different phase II detoxifying ‍enzymes such as glutathione-S-transferase (p<0.01) and superoxide dismutase (p<0.01) in skin cytosol when measured ‍after 15 days and also after 12 weeks of the first 7,12-dimethylbenz (a) anthracene treatment. Lipid peroxidation ‍measured with reference to thiobarbituric acid reactive substances in skin microsomes was significantly inhibited ‍(p<0.05) in a dose dependent manner by diphenylmethyl selenocyanate. Considerable inhibition of the level of nitric ‍oxide production in peritoneal macrophages was observed after 12 weeks (p<0.05). ‍Thus the compound appears to exert chemopreventive activity in terms of papilloma formation, which may be ‍through modulation of cutaneous lipid peroxidation, the phase II detoxifying enzyme system and nitric oxide ‍production.     

Selected Risk Factors,Human Papillomavirus Infection and the P53 Codon 72 Polymorphism in Patients with Squamous Intraepithelial Lesions in Northeastern Thailand

Risk factors for cervical squamous intraepithelial lesions (SIL) including human papillomavirus (HPV) infection ‍and the p53 codon 72 polymorphism were investigated in a case-control study with 103 cases and 105 controls in ‍Northeastern Thailand. Increased risk for SIL was observed for age at menarche (odds ratio (OR) = 2.2; p<0.005), ‍age at the first sexual intercourse (OR=2.4; p<0.05), number of sexual partners (OR=2.7; p<0.005) and partners’ ‍smoking history (OR=2.3-3.2; p<0.01). Prevalence of malignant type of HPV infection in the control and SIL groups ‍was 18.1% and 60.2%, respectively. HPV infection significantly increased risk for SIL 6.8-fold (p<0.001). HPV-16 ‍infection was the commonest (31 out of 62 carriers) in SIL patients and highly associated with risk. The p53 codon 72 ‍polymorphism was not identified as a genetic risk for SIL in this study, as demonstrated in Thai cervical cancer. ‍Therefore, to prevent cervical neoplasia or HPV infection, inclusion of knowledge on sexual behavior and effects of ‍smoking into public health programs is important and, at the same time, a nation-wide screening scheme for cervical ‍abnormalities including HPV-typing is a high priority in Thailand.     

Ethanolic Neem Leaf Extract Protects Against N-methyl –N’- nitro-N-nitrosoguanidine-induced Gastric Carcinogenesis in Wistar Rats

We evaluated the effects of ethanolic neem leaf extract on N-methyl-N’-nitro-N-nitrosoguanidine (MNNG)-induced ‍gastric carcinogenesis in Wistar rats. The extent of lipid peroxidation and the status of the antioxidants superoxide ‍dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione-Stransferase ‍(GST) in the stomach, liver and erythrocytes were used as biomarkers of chemoprevention. Animals ‍were divided into four groups of six animals each. Rats in group 1 were given MNNG (150 mg/kg bw) by intragastric ‍intubation three times with a gap of 2 weeks in between the treatments. Rats in group 2 administered MNNG as in ‍group 1, in addition received intragastric intubation of ethanolic neem leaf extract (200 mg/kg bw) three times per ‍week starting on the day following the first exposure to MNNG and continued until the end of the experimental ‍period. Group 3 animals were given ethanolic neem leaf extract alone, while group 4 served as controls. All the ‍animals were killed after an experimental period of 26 weeks. Diminished lipid peroxidation in the stomach tumour ‍tissue was associated with enhanced antioxidant levels. In contrast to tumour tissue, enhanced lipid peroxidation ‍with compromised antioxidant defences was found in the liver and erythrocytes of tumour bearing animals. ‍Administration of ethanolic neem leaf extract significantly reduced the incidence of stomach tumours, modulated ‍lipid peroxidation and enhanced antioxidant status in the stomach, liver and blood. From the results of our study, we ‍suggest that ethanolic neem leaf extract may exert its chemopreventive effects by modulating lipid peroxidation and ‍enhancing the antioxidant status in the stomach, liver and erythrocytes. ‍     

Relationship between Obesity and Serum Markers of Oxidative Stress and Inflammation in Japanese

The present study was conducted to assess the relationship between obesity and serum levels of C-reactive protein ‍(CRP), carotenoids, oxidized LDL (oxLDL), oxidized LDL antibodies (oLAB), and leptin in Japanese residents. ‍The subjects were 158 males and 158 females aged 40-79 years, and living in Hokkaido, Japan, who attended a ‍health examination screening. Serum levels of CRP, oxLDL, oLAB, and leptin were measured by enzyme-linked ‍immunosorbent assay (ELISA) and serum carotenoid levels were measured by high-performance liquid ‍chromatography (HPLC). Body mass index (BMI) was calculated as body weight (kg) divided by height (m) squared ‍and obesity was defined as BMI of 25 or more (kg/m2). ‍Serum levels of CRP and leptin were significantly higher in the obese group than in their non-obese counterparts ‍in both genders. Serum levels of â-carotene and â-cryptoxanthin were lower in the obese individuals, especially in ‍females. While values for oxLDL and oLAB did not significantly vary. BMI was positively correlated with logtransformed ‍serum levels of CRP and leptin in both genders (males: r=0.231, p<0.05; females: r=0.305, p<0.001). In ‍females, moreover, BMI was negatively correlated with log-transformed serum levels of â-carotene, zeaxanthin/ ‍lutein, and â-cryptoxanthin (r=-0.244, p<0.01; r=-0.200, p<0.05; r=-0.207, p<0.01, respectively). ‍Significantly higher odds ratios (ORs) for high serum levels of CRP (males: OR=2.12; females: OR=3.96) and ‍leptin (males: OR=3.83; females: OR=9.07) were observed in obese versus non-obese men and women, after adjusting ‍for various confounding factors. Significantly lower adjusted odds ratios for high serum levels of á- and â-carotenes ‍(males: OR=0.23, 0.33; females: OR=0.35, 0.39, respectively) were also observed in the obese as compared to the ‍non-obese group. ‍In conclusion, obesity is highly associated with states of oxidative stress and low-grade inflammation in Japanese ‍residents, suggesting that these latter might play an important role in the association between a high BMI and ‍certain cancers as well as coronary heart disease (CHD). ‍     

Chemopreventive Action of Emblica Officinalis on Skin Carcinogenesis in Mice

Chemoprevention with food phytochemicals is currently regarded as one of the most important strategies for ‍cancer control. Emblica officinalis (Family: Euphorbiaceae) indigenous to India, is valued for its unique tannins and ‍flavanoids, which contain very powerful antioxidant properties. The inhibition of tumor incidences by fruit extract ‍of this plant has been evaluated on two-stage process of skin carcinogenesis in Swiss albino mice, induced by a single ‍application of 7, 12-dimethyabenz(a)anthrecene (100 ìg/ 100 ìl acetone), and two weeks later, promoted by repeated ‍application of croton oil (1% in acetone/thrice a week) till the end of the experiment (16 weeks). The tumor incidence, ‍tumor yield, tumor burdon and cumulative number of papillomas were found to be higher in the control (without ‍EO treatment) as compared to experimental animals (EO treated). The differences in the values of the results of ‍experimental groups were statistically analysed and found to be significant in comparison to the control group (p< ‍0.05). The present study demonstrates the chemopreventive potential of Emblica officinalis fruit extract on DMBA ‍induced skin tumorigenesis in Swiss albino mice. ‍     

Strategies for advancement of short-term mutagenicity tests: on the optimal ionic strength for the liver microsomal assay.

The aim of this work was to optimize the ionic strength (tau) in the liver microsomal assay (LMA) in performing short-term genotoxicity tests. tau optimization would increase the sensitivity (i.e. decrease false negatives) and at the same time increase the specificity (decrease false positives). Such optimization depends upon the relative activities and stabilities of the liver polysubstrate cytochrome P450- and FAD-containing monooxygenase-dependent metabolizing enzymes present in the incubation mixtures. With regard to phase-I pathway, the expression of various P450-like activities (IA1, IA2, IIB1, IIE1, IIIA P450 classes) and thiobenzamide s-oxidase (as FAD-MFO marker), were examined in terms of their exact incubation conditions for the LMA during a period of preincubation (1 h) over the tau range 0.06-1.40. As a comparison with the phase-II pathway, the behaviour of glutathione S-transferases (total and pi class), glutathione S-epoxide transferase, epoxide hydrolase and UDP-glucuronosyl transferase were studied. Lipid peroxidation (LP) was also determined. Experiments were performed on S9 fractions derived from sodium phenobarbital, beta-naphthoflavone, isosafrol, ethanol and pregnenolone 16-alpha carbonitrile super-induced mouse liver. The maximal value of the mean specific activity (Asp), up to a 46% increase, was found at tau = 0.864 for oxidative reactions considered. On the contrary, a slight modulation of Asp for post-oxidative reactions was seen. LP was not changed appreciably by varying tau. In vitro DNA binding of the well-known premutagenic agent [14C]dimethylnitrosamine ([14C]DMNA), mediated by mouse hepatic microsomal enzymes, showed a significant increase of specific activity at tau = 0.864 (2.25-fold) compared to the usual tau (0.06) used. Additional confirmation of these results stems from mutagenesis experiments using DMNA on the diploid D7 strain of Saccharomyces cerevisiae as a biological test system. Indeed, a significant enhancement of mitotic gene conversion (up to 1.8-fold), mitotic crossing-over (2.6-fold) and reverse point mutation (2.6-fold) frequencies was achieved at tau = 0.86 compared to tau = 0.06 (traditional). These data show that tau = 0.86 can provide more convenient conditions for in vitro bioactivation (as exemplified by an increased Asp phase-I/Asp phase-II ratio), as well as DNA binding and genotoxic response.     

Elimination of Deleterious Effects of Free Radicals in Murine Skin Carcinogenesis byBlack Tea Infusion,Theaflavins & Epigallocatechin Gallate

In recent years, numerous reports have been published on the identification of novel, naturally occurring ‍antioxidants from plants, animals, microbial sources and processed food products. Most natural antioxidants are ‍phenolic compounds, which have a modulatory role on physiological functions and biotransformation reactions ‍involved in the detoxification process, thereby affording protection from cytotoxic, genotoxic and metabolic actions ‍of environmental toxicants. As part of our program on evaluation of food, beverage and traditional medicinal plants ‍for their anticarcinogenic activity, the present report deals with the evaluation of aqueous infusion of Black tea ‍(Camellia sinensis), Black tea extract (80% Theaflavins) & EGCG on mice exposed to the chemical carcinogen ‍DMBA. All the four detoxification enzymes studied viz, GST, GPx, SOD and CAT were found to be activated to ‍different degrees following treatment with black tea and two of its active compounds. The activation of the enzymes ‍was accompanied by significant reduction in lipid peroxidation. The effect on apoptosis and cell proliferation was ‍also studied in mice skin following administration of DMBA. Theaflavins, and EGCG significantly inhibited cell ‍proliferation and induced apoptosis. The observation suggests chemopreventive potential of black tea infusion, ‍black tea extract Theaflavins and the compound EGCG.‍     

Inhibitory Effects of Crude α-Mangostin,a Xanthone Derivative,on Two Different Categories of Colon Preneoplastic Lesions Induced by 1, 2-dimethylhydrazine in the Rat

The purpose of this study was to examine whether crude á-mangostin (a major xanthone derivative in mangosteen ‍pericarp (Garcinia mangostana)) has short-term chemopreventive effects on putative preneoplastic lesions involved ‍in rat colon carcinogenesis. The crude preparation was obtained by simple recrystallization of an ethylacetate ‍extract of mangosteen pericarps. A total of 33 five-week-old male F344 rats were randomly divided into 5 experimental ‍groups. Rats in groups 1-3 were given a subcutaneous injection of 1,2-dimethylhydrazine (DMH)(40 mg/kg body ‍weight) once a week for 2 weeks. Starting one week before the first injection of DMH, rats in groups 2 and 3 were fed ‍a diet containing 0.02% and 0.05% crude á-mangostin, respectively, for 5 weeks. Rats in group 4 also received the ‍diet containing 0.05% crude á-mangostin, while rats in group 5 served as untreated controls. The experiment was ‍terminated 5 weeks after the start. Dietary administration of crude á-mangostin at both doses significantly inhibited ‍the induction and/or development of aberrant crypt foci (ACF) (P<0.05 for 0.02% crude á-mangostin, P<0.01 for ‍0.05% crude á-mangostin), when compared to the DMH-treated group (group 1). Moreover, treatment of rats with ‍0.05% crude á-mangostin significantly decreased dysplastic foci (DF) (P<0.05) and â-catenin accumulated crypts ‍(BCAC) (P<0.05), to below the group 1 values. The proliferating cell nuclear antigen (PCNA) labeling indices of ‍colon epithelium and focal lesions in groups 2 and 3 were also significantly lower than in group 1 and this effect ‍occurred in a dose dependent manner of the crude á-mangostin. This finding that crude á-mangostin has potent ‍chemopreventive effects in our short-term colon carcinogenesis bioassay system suggests that longer exposure might ‍result in suppression of tumor development. ‍     

5-Azacytidine carcinogenesis in BALB/c mice

5-Azacytidine, a drug used in the treatment of acute leukaemias and beta-thalassemia, was administered i.p. to BALB/c mice at a dose of 2.0 mg/kg body wt. once a week for 50 weeks to test its carcinogenicity. The treatment induced a significant increase in lung tumours (males P less than 0.001, females P less than 0.05), lymphomas (males P less than 0.01, females P less than 0.01), skin tumours (males P less than 0.05, females P less than 0.01) in both sexes and mammary carcinomas (P less than 0.01) and a variety of other tumours in female mice. These results, with other investigations reported in literature, suggest that 5-azacytidine is carcinogenic in mice.     

Chemoprevention by Butea Monosperma of Hepatic Carcinogenesis and Oxidative Damage in Male Wistar Rats

In this communication, we document chemopreventive effects of Butea monosperma extract on hepatic ‍carcinogenesis and on tumor promoter induced markers and oxidative stress in male Wistar rats. Treatment of male ‍Wistar rats for five consecutive days with 2-AAF i.p. induced significant hepatic toxicity, oxidative stress and ‍hyperproliferation. Pretreatment of B.monosperma extract (100 and 200 mg/kg body weight) prevented oxidative ‍stress by restoring the levels of antioxidant enzymes and also prevented toxicity at both doses. The promotion ‍parameters induced (ornithine decarboxylase activity and DNA synthesis) by 2-AAF administration in diet with ‍partial hepatectomy (PH) were also significantly suppressed dose dependently by B. monosperma. Thereafter, we ‍proceeded with studies on rat liver carcinogenesis. After fourteen days of DEN treatment, dietary administration of ‍2-AAF with PH resulted in a 100% incidence of tumors in the animals. However, B.monosperma caused reduction in ‍the number of tumors/ rat and percentage of tumor bearing rats at the end of the study, as confirmed histologically. ‍Thus, our data suggest that B.monosperma extract is a potent chemopreventive agent which suppresses 2-AAFinduced ‍hepatic carcinogenesis and oxidative damage in Wistar rats. The protective activity of the plant might be ‍due to the two major constituents (butrin and isobutrin).     

Immunomodulatory Activities of Centella asiatica and Rhinacanthus nasutus Extracts

Centella asiatica (CA) and Rhinacanthus nasutus (RN )have been used for treatment of various illnesses, but the ‍mechanisms of action remain largely unknown. This study focused on the influence of CA and RN extracts on cellmediated ‍and humoral immune responses. In human peripheral blood mononuclear cells (PBMCs), CA (water ‍extract) and RN (water and ethanol extracts) significantly increased proliferation and the production of IL-2 and ‍TNF-á. In contrast, an ethanol extract of CA inhibited human PBMC mitogenesis and the production of IL-2 and ‍TNF-á. BALB/c mice treated with CA extracts (100 mg/kg bw) showed higher responses to both primary and ‍secondary antibodies against BSA when compared with non-treated group. Only the secondary antibody response ‍was increased in RN extract-treated mice. The present study revealed immunomodulating activity of CA and RN ‍extracts with regard to both non-specific cellular and humoral immune responses. The data available to date suggest ‍that they may have chemopreventive or anticancer potential.     

Chemopreventive Activity of Turmeric Essential Oil and Possible Mechanisms of Action

This study aimed to evaluate the antimutagenic and anticarcinogenic activity of turmeric essential oil as well as to establish biochemical mechanisms of action. Antimutagenicity testing was accomplished using strains and known mutagens with and without microsomal activation. Anticarcinogenic activity was assessed by topical application of 7, 12 – dimethylbenz[a]anthracene (DMBA) as initiator and 1% croton oil as promoter for the induction of skin papillomas in mice. Inhibition of p450 enzymes by TEO was studied using various resorufins and aminopyrene as substrate. Turmeric essential oil (TEO) showed significant antimutagenic activity (p<0.001) against direct acting mutagens such as sodium azide (NaN3), 4-nitro-O-phenylenediamine (NPD) and N-methyl-N-nitro N’nitrosoguanine (MNNG). TEO was found to have significant antimutagenic effect (>90%) against mutagen needing metabolic activation such as 2-acetamidoflourene (2-AAF). The study also revealed that TEO significantly inhibited (p<0.001) the mutagenicity induced by tobacco extract to Salmonella TA 102 strain. DMBA and croton oil induced papilloma development in mice was found to be delayed and prevented significantly by TEO application. Moreover TEO significantly (P<0.001) inhibited isoforms of cytochrome p450 (CYP1A1,CYP1A2, CYP2B1/2, CYP2A, CYP2B and CYP3A) enzymes in vitro, which are involved in the activation of carcinogens. Results indicated that TEO is antimutagenic and anticarcinogenic and inhibition of enzymes (p450) involved in the activation of carcinogen is one of its mechanisms of action.     

Anti-tumour Promoting Activity of Diphenylmethyl Selenocyanate Against Two-stage Mouse Skin Carcinogenesis

Epidemiological, clinical and experimental evidence collectively suggests that Se in different inorganic and organic ‍forms provides a potential cancer chemopreventive agent, active against several types of cancer. It can exert preventive ‍activity in all the three stages of cancer: initiation, promotion and progression. Literature reports revealed that ‍organoselenocyanates have more potential as chemopreventive agents than inorganic forms due to their lower toxicity. ‍In our previous report we showed chemopreventive efficacy of diphenylmethyl selenocyanate during the initiation ‍and pre- plus post-initiation phases of skin and colon carcinogenesis process. The present study was undertaken to ‍explore the anti-tumour promoting activity of diphenylmethyl selenocyanate in a 7,12-dimethylbenz (a) anthracene ‍(DMBA)-croton oil two-stage skin carcinogenesis model. The results obtained showed significant (p<0.01) reduction ‍of the incidence and number of skin papillomas, precancerous skin lesions, along with significant (p<0.01) elevation ‍of phase II detoxifying enzymes (GST, Catalase and SOD) and inhibition of lipid peroxidation in liver and skin. ‍Thus, the present data strongly suggest that diphenylmethyl selenocyanate also has the potential to act as antitumour ‍promoter agent in a two-stage skin carcinogenesis mouse model, pointing to possible general efficacy.     

Epidemiology of Breast Cancer in Females of Reproductive Age in Kyrgyzstan

The goal of this research was to study breast cancer morbidity in females of reproductive age in Kyrgyzstan. ‍Information on patients was obtained from the National Center of Oncology under the Ministry of Health and the ‍National Statistics Committee of the Kyrgyz Republic. The research was retrospective and covered the period from ‍1995-2002. Cancer morbidity ratios were calculated for reproductive age according to standard methods of medicobiological ‍statistics. The breast cancer morbidity in the country’s female population was determined as 12.3±0.2/ ‍100,000. The research revealed ethnic specificity: in Russians (crude rate, 32.9±2.1) was higher (p<0.001), than in ‍Kyrgyz and Uzbek females, who demonstrated equal crude incidence rates of – 8.0±0.6. The dynamics over time ‍showed increase in Kyrgyz and Uzbek females but decrease in Russians. Age ratios analysis showed higher morbidity ‍in later reproductive age (40-49 years), with a statistically significant difference (p<0.001) between ethnic Europeans ‍and Asians. ‍     

Chemopreventive efficacy of Moringa oleifera pods against 7, 12-dimethylbenz[a]anthracene induced hepatic carcinogenesis in mice

Oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage in a variety of liver disorders. Hence there is a great demand for the development of agents with potent antioxidant effect. The aim of the present investigation is to evaluate the efficacy of Moringa oleifera as a hepatoprotective and an antioxidant against 7, 12-dimethylbenz[a]anthracene induced hepatocellular damage. Single oral administration of DMBA (15 mg/kg) to mice resulted in significantly (p<0.001) depleted levels of xenobiotic enzymes like, cytochrome P450 and b5. DMBA induced oxidative stress was confirmed by decreased levels of reduced glutathione (GSH) and glutathione-S-transferase (GST) in the liver tissue. The status of hepatic aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) which is indicative of hepatocellular damage were also found to be decreased in DMBA administered mice. Pretreatment with the Moringa oleifera (200 and 400 mg/kg) orally for 14 days significantly reversed the DMBA induced alterations in the liver tissue and offered almost complete protection. The results from the present study indicate that Moringa oleifera exhibits good hepatoprotective and antioxidant potential against DMBA induced hepatocellular damage in mice that might be due to decreased free radical generation.     

Comparative Epidemiological Characteristics of Oesophageal Adenocarcinoma and other Cancers of the Oesophagus and Gastric Cardia

Secular trends and epidemiological characteristics of 1,581 oesophageal cancers, diagnosed in South Australian ‍residents in 1977-2000, were analysed by histological type and diagnostic period, using multivariable Poisson regression ‍and logistic regression. The age-adjusted incidence of squamous cell carcinoma did not vary significantly by diagnostic ‍period, either in males (p=0.195) or females (p=0.087). By comparison, variations were observed for adenocarcinomas ‍in males (p<0.001) and females (p=0.015), with an increase in age-adjusted incidence of 169% for males and 150% ‍for females between 1977-81 and 1997-2000. Most of these increases occurred in the 1990s. Secular differences were ‍not evident for tumours of other or unknown histological type. The ratio of adenocarcinomas to squamous cell ‍carcinomas was higher in patients who were aged 80 years or more, male, residents of high socio-economic areas, ‍and those born in the United Kingdom/Ireland. Conversely, relatively low ratios presented for patients born in ‍Southern and other parts of Europe. These differences by country of origin accord with differences between the ‍national incidence rates for these countries, as indicated by international data. Differences in secular trend and ‍country of birth between adenocarcinomas of the oesophagus and gastric cardia suggest that they are not expressions ‍of the same disease. Preventive implications of these results are discussed. ‍     

Inhibition of Metastatic Lung Cancer in C57BL/6 Mice byMarine Mangrove Rhizophora apiculata

Metastasis is one of the hallmarks of malignant neoplasms and is the leading cause of death in many cancerpatients. A major challenge in cancer treatment is to find better ways to specifically target tumor metastasis.In this study, the anti-metastatic potential of the methanolic extract of Rhizophora apiculata (R.apiculata) wasevaluated using the B16F-10 melanoma induced lung metastasis model in C57BL/6 mice. Metastasis was inducedin C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Simultaneoustreatment with R.apiculata extract (10 mg/kg b.wt (intraperitoneal) significantly (p<0.01) inhibited pulmonarytumor nodule formation (41.1 %) and also increased the life span (survival rate) 107.3 % of metastatic tumorbearing animals. The administration of R.apiculata extract significantly (p<0.01) reduced biochemical parameterssuch as lung collagen hydroxyproline, hexosamine, uronic acid content, serum nitric oxide (NO), γ-glutamyltranspeptidase (GGT) and sialic acid levels when compared to metastasis controls. These results correlated withlung histopathology analysis of R.apiculata extract treated mice showing reduction in lung metastasis and tumormasses. Taken together, our findings support that R.apiculata extract could be used as a potential anti-metastasisagent against lung cancer.