Bone Marrow Cell Therapy on 1,2-Dimethylhydrazine (DMH)-Induced Colon Cancer in Rats.

BACKGROUND/AIMS: Stem cell based therapies are being under focus due to their possible role in treatment of various tumors. Bone marrow stem cells believed to have anticancer potential and are preferred for their activities by stimulating the immune system, migration to the site of tumor and ability for inducting apoptosis in cancer cells. The current study was aimed to investigate the tumor suppressive effects of bone marrow cells (BMCs) in 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats. METHODS: The rats were randomly allocated into four groups: control, BMCs alone, DMH alone and BMCs with DMH. BMCs were injected intrarectally while DMH was injected subcutaneously at 20 mg/kg body weight once a week for 15 weeks. Histopathological examination and gene expression of survivin, ß-catenin and multidrug resistance-1 (MDR-1) by real-time reverse transcription-polymerase chain reaction (RT-PCR) in rat colon tissues. This is in addition to oxidative stress markers in colon were performed across all groups. RESULTS: The presence of aberrant crypt foci was reordered once histopathological examination of colon tissue from rats which received DMH alone. Administration of BMCs into rats starting from zero-day of DMH injection improved the histopathological picture which showed a clear improvement in mucosal layer, few inflammatory cells infiltration periglandular and in the lamina propria. Gene expression in rat colon tissue demonstrated that BMCs down-regulated survivin, ß-catenin, MDR-1 and cytokeratin 20 genes expression in colon tissues after colon cancer induction. Amelioration of the colon status after administration of MSCs has been evidenced by a major reduction of lipid peroxidation, nitric oxide, and increasing of glutathione content and superoxide dismutase along with catalase activities. CONCLUSION: Our findings demonstrated that BMCs have tumor suppressive effects in DMH-induced colon cancer as evidenced by down-regulation of survivin, ß-catenin, and MDR-1 genes and enhancing the antioxidant activity.

Graphene oxide nanosheets induced genotoxicity and pulmonary injury in mice.

Graphene and graphene-related materials have broadly applied in biomedical purposes due to their unique properties, thus safety evaluation of them is crucial. This study was performed to explore the genotoxic and pulmonary toxic potential of different doses of graphene oxide nanosheets' (GOs) in mice.A total of 90 male mature mice were randomly divided into six groups of fifteen mice per each, five groups were intraperitoneally injected by GO at doses of 10, 50, 100, 250 and 500µg/kg b.w once weekly in addition to the control group that was injected intraperitoneally with 0.2ml saline solution. Five animals from each group were euthanized after 7, 28 and 56days post treatment. Evaluation of genotoxicity was performed through detection of chromosomal aberrations in bone marrow while assessment of lung injury was made by determination of DNA fragmentation in lung specimens using the alkali Comet assay, pulmonary oxidative markers estimation and finally histopathological investigations. Results revealed that GOs induced variable structural chromosomal aberrations (SCA) in bone marrow and DNA damage of lung cells that were time and dose dependent and represented by increase in%DNA in comet tail, tail moment and tail length and decrease in% head DNA in nuclei of lung of GOs-treated mice versus control groups in addition, GOs induced various changes in pulmonary oxidative stress parameters that were affected by dose and duration of treatment compared with the control as well as various pulmonary histopathological alterations were detected indicating lung injury. CONCLUSION: GO potentiate the induction of genotoxicity and pulmonary injury in mice in time and dose dependent manner.

Assessment of anti-mutagenic, anti-histopathologic and antioxidant capacities of Egyptian bee pollen and propolis extracts.

Bee pollen and propolis are popular, traditional health foods. The objective of the current study was to investigate the anti-mutagenic, anti-histopathologic and antioxidant effects among water extracts of Egyptian bee pollen (WEBP) and brown powder of water-soluble derivative propolis (WSDP) on cisplatin (CDDP) induced hepatic, renal, testicular and genotoxicity in male albino mice (Mus muscullus), in addition to their effects on the oxidant/antioxidant status in the tested organs. Hepatic, renal and testicular dysfunctions were evaluated histologically; while genotoxicity and cytotoxicity were evaluated by the bone marrow chromosomal aberration assay and mitotic index, respectively. Moreover, oxidative stress was explored via determination of lipid peroxidation, catalase activity and the concentration of the reduced form of glutathione. The treatment of mice with WEBP and WSDP at doses 140 and 8.4 mg/kg b. wt./day, respectively for 14 days simultaneously with CDDP (2.8 mg/kg b. wt.) resulted in significant protection. The positive control animals taken CDDP alone showed toxic histological and genetical manifestations (at P < 0.05) accompanied with an elevated content of peroxidized lipid and lowered catalase activity and glutathione concentration in the homogenate of liver, kidney and testis tissues (at P < 0.001). These toxic side effects in all tested organs were greatly ablated with a significant reduction in lipid peroxidation level and elevation in catalase activity and glutathione concentration (P < 0.001) when using both WEBP and WSDP. On the basis of the present assays, Bee pollen appears more potent in exerting an ameliorative effect and this effect was more pronounced in testis.

Role of cyclins A and E in endometrial carcinogenesis in breast cancer patients under tamoxifen treatment.

PURPOSE: The objective of our study was to determine the relevance of cyclins A and E overexpression in endometrial carcinogenesis in hormone receptor-positive breast cancer patients under tamoxifen therapy. EXPERIMENTAL DESIGN: We assessed expression of cyclins A and E in Endometrial cytology samples collected from 36 ER and PR positive breast cancer patients; under tamoxifen treatment by using the Tao-brush non-invasive brushing cytology technique. Cyclins were detected in the collected samples by means of immuno-cytochemistry. The patients included in this study are a cohort of 36 breast cancer patients who were operated upon at the National Cancer Institute - Cairo University in the period from February 2006 to May 2008 and received tamoxifen (TAM) as part of their adjuvant treatment. RESULTS: Cyclins A and E were expressed in 17 and 15 of the 36 collected endometrial cytology samples (47.2% and 41.6% respectively). Expression of cyclins A and E was highly correlated to Tamoxifen exposure duration (32 and 43 months respectively) p < 0.001. Tamoxifen median exposure duration was shortened to 21 months in cases showing positivity for either markers, while in cases showing positivity for both cyclins, the median exposure duration was longer (44.5 months) (p < 0.001). Neither cyclin A nor E was detected before median tamoxifen exposure duration of 11 months. Endometrial carcinoma cases had the longest Tamoxifen exposure duration (60 months). CONCLUSION: Cyclins A and E expression is involved in the carcinogenesis of endometrium in women with breast cancer and under tamoxifen-treatment. Follow up of the patients using these 2 markers is highly recommended starting from the 12th month.

Alleviation of genotoxic effects of cyclophosphamide using encapsulation into liposomes in the absence or presence of vitamin C.

Cyclophosphamide (CP) is a widely used anticancer and immunosuppressant that induces oxidative stress. To ameliorate the side effects resulted from CP treatment, liposomes were tested as an efficient drug delivery system with or without vitamin C as an antioxidant. CP resulted in clastogenic and cytotoxic effects that significantly increased for the total chromosomal aberrations as well as the numerical ones in the CP group (150.8 and 6, respectively) than the control group (6.6 and 0.0) as mean values at p < 0.05. Micronucleus assay showed a significant increased micronucleated polychromatic erythrocytes percentage (MNPCEs% = 11.7%) and a significant decrease of polychromatic to normochromatic erythrocytes ratio (0.551) when compared to the group treated with liposomised CP and vitamin C (3.44%; 0.795, respectively) at p < 0.05. Also, the total glutathione S-transferase activity as a body antioxidant enzyme was decreased from 52.2 in the control to 16.09 nmol/min/mg protein in CP group at p < 0.05, while the highly significant amelioration results were observed in the liposomised vitamin C and CP group (40.88 nmol/min/mg protein). Our findings support the potential use of CP in a liposomal formulation doped with vitamin C to diminish the potential side effects of the agent.

Protective effects of garlic and silymarin on NDEA-induced rats hepatotoxicity.

BACKGROUND: The present study was conducted to investigate the chemopreventive effects of garlic extract and silymarin on N-nitrosodiethylamine (NDEA) and carbon tetrachloride (CCl(4))-induced hepatotoxicity in male albino rats. METHODS AND RESULTS: Animals were pretreated with garlic, silymarin or both for one week prior to the injection of NDEA. Then animals received a single injection of NDEA followed by weekly subcutaneous injections of CCl(4) for 6 weeks. Oral administration was then continued along with the injection of CCl(4) for the duration of the experiment. Serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), hepatic lipid peroxidation (LPO), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione-S-transferase (GST) and glutathione reductase (GSR) were measured. Injection of NDEA induced a significant elevation in serum AST, ALT and ALP. In the liver, NDEA increased oxidative stress through the increase in LPO and decrease in SOD, and GSH-dependent enzymes. Although administration of garlic or silymarin significantly reduced the liver toxicity, combined administration was more effective in preventing the development of hepatotoxicity. CONCLUSION: These novel findings suggest that silymarin and garlic have a synergistic effect, and could be used as hepatoprotective agents against hepatotoxicity.

Beta-glucan inhibits the genotoxicity of cyclophosphamide, adriamycin and cisplatin.

The inhibitory effects of beta-glucan (betaG), one of the biological response modifiers, on the induction of chromosomal aberrations in the bone marrow and spermatogonial cells of mice treated with various anti-neoplastic drugs were investigated. beta-Glucan (100 mg/kg bw, i.p.) pre-treatment reduced the total number of cells with structural chromosomal aberrations scored after the treatment with cyclophosphamide (CP) (2.5 mg/kg bw, i.p.) adriamycin (ADR) (12 mg/kg bw, i.p.) and cis-diamminedichloroplatinum-II (cisplatin) (5 mg/kg bw, i.p.) by about 41.1, 26.9 and 57.7% in bone marrow and 44.4, 55 and 57.1% in spermatogonial cells, respectively. This protective effect of beta-glucan could be attributed to its scavenging ability to trap free-radicals produced during the biotransformation of these anti-neoplastic drugs. Beta-glucan also markedly restored the mitotic activity of bone marrow cells that had been suppressed by the anti-neoplastic drugs. These results indicate that in addition to the known immunopotentiating activity of beta-glucan, it plays a role in reducing genotoxicity induced by anti-neoplastic drugs during cancer chemotherapy.