Effect of Balanites aegyptiaca on Ehrlich Ascitic carcinoma growth and metastasis in Swiss mice.

The role of Balanites aegyptiaca (B. aegyptiaca) on development and growth of Ehrlich Ascitic carcinoma (EAC) and metastasis (liver and spleen) was evaluated. Balanite (400mg/kg; 10mg in 0.1ml/mouse) was given daily over a period of two weeks started 24h before intraperitoneal injection of EAC (2×10(6)/once). The present study deals with the effect of B. aegyptiaca on the growth of transplantable ascetic tumor, life span of EAC-bearing mice, hepatocellular and splenic histology. Antioxidant and biochemical changes as well as p53 genes expression were recorded. B. aegyptiaca extracts inhibited tumor growth and proliferation in ascetic fluid through a significant decrease in tumor volume, total cell volume, and viable cell count and prolonged the life span of mice. Also, it significantly decreased the levels of lipid peroxidation and increased SOD, CAT levels and P53 expression. Also, balanite inhibited either tumor invaded/or affected hepatic and splenic tissue. This result gives a new insight on beneficial effect of B. aegyptiaca in primary and secondary loci of Ehrlich Ascitic tumor through its antioxidant effect.

Expression of insulin-like growth factor-II, matrix metalloproteinases, and their tissue inhibitors as predictive markers in the peripheral blood of HCC patients.

BACKGROUND/AIM: Elevated relative expression of insulin-like growth factor-II (IGF-II) was observed in hepatocellular carcinoma (HCC) liver tissues with a role in neovascularization and associated with poor prognosis. IGF-II is influenced by the proteolytic cleavage of IGF-binding protein 3 and by matrix metalloproteinases (MMP), which are further regulated by their tissue inhibitors tissue inhibitor of metalloprotienase-1 (TIMP-1). Our aim is to study new molecular markers for HCC. PATIENTS/METHODS: RNA was extracted from the peripheral blood for evaluating the relative expression of IGF-II, MMP-9, and TIMP-1 in correlation with clinical staging of 39 HCC patients and 15 healthy controls using TaqMan real-time PCR. RESULTS: The relative expression of IGF-II and MMP-9 mRNA were significantly elevated in HCC patients compared with healthy controls; P-value <0.0001 for both. There was a significant correlation between MMP-9 and different HCC stages. On the other hand, TIMP-1 was significantly down-regulated in HCC patients; P = 0.0003 with the elevation of the IGF-II/TIMP-1 ratio. Significant correlation between TIMP-1 and HCC Stage III and Stage IV was found; P-value = 0.0138. CONCLUSION: These results highlight the importance of profiling the expression of IGF-II, MMP-9, and TIMP-1 in the peripheral blood as prognostic molecular biomarkers in HCC.

Immunodiagnostic potential of mucin (MUC2) and Thomsen-Friedenreich (TF) antigens in Egyptian patients with colorectal cancer.

OBJECTIVE: Colorectal cancer (CRC) is more common in developed countries and is the third most common cancer among both men and women. CRC provides an attractive model of tumour biology with normal mucosa to adenoma to carcinoma sequence. The TF-antigen (Thomsen-Friedenreich) can be identified by galactose oxidase-Schiff's (GOS) reaction either on tissues or on rectal mucus samples from patients with CRC. TF antigen is expressed in the neoplastic mucosa and not expressed in colonic mucosa of normal subjects. Apomucins play important role in cell signalling and their specific pattern of expression during the different steps of tumor progression toward adenocarcinoma suggests that they play significant roles in tumorigenesis. The family of secreted mucins including MUC2 is contributing in mucus formation to protect underlying epithelia against diverse injuries. The current study was investigated the expression of MUC2 and TF antigens in patients with adenoma and CRC. MATERIALS AND METHODS: MUC2 and TF antigen expressions were detected immunohistochemically in CRC biopsies using specific monoclonal antibodies. Moreover, the TF antigen was invesigated using GOS reaction. RESULTS: The results showed that in normal colonic specimens, MUC2 expression was detected in 20%, while TF antigen was completely negative in 100% of samples as detected by GOS and immunohistochemistry using anti-TF monoclone. Expressions of MUC2, and TF antigen as detected by GOS and anti-TF monoclone were positive in 96%, 80%, and 60% respectively in cases with adenoma. On the other hand, in cases with adenocarcinoma, the expression of MUC2 was seen in 92% of cases, while TF antigen was observed in 84% and 60% of cases as detected by GOS and immunohistochemically respectively. CONCLUSIONS: Thus, it is concluded that the expression of MUC2 and TF antigens are altered during CRC carcinogenesis. Furthermore, MUC2 and TF antigens may have a diagnostic and or prognostic potential in CRC.

Serum levels of TNF-alpha and antioxidant enzymes and placental TNF-alpha expression in unexplained recurrent spontaneous miscarriage.

It has been proposed that many factors have been implicated in the pathogenesis of unexplained recurrent spontaneous miscarriage (URSM). The objective of this study was to evaluate the levels of some antioxidants, tumor necrosis factor-alpha (TNF-alpha), luteinizing (LH) and follicle-stimulating hormone (FSH) in URSM. Serum levels of superoxide dismutase (SOD), catalase (CAT), LH, FSH as well as TNF-alpha in serum and the expression of TNF-alpha positive cells in placental tissues, were assayed in women suffering from unexplained first trimester miscarriage. Two groups were included, the first was represented by 16 women with URSM (number of abortions: 3-5) and the second one included 24 women with URSM (number of abortions > 5). The control groups included 20 women within their first trimester of pregnancy and 20 non pregnant healthy females within their follicular phase. The obtained results showed a highly significant decrease in serum levels of SOD and CAT, in the URSM groups compared to control groups (p < 0.05 for each comparison). Higher serum levels of TNF-alpha were detected in URSM groups compared to control groups (p < 0.05 for each comparison). A significant increase in serum levels of LH was encountered between URSM groups compared to control groups; on the other hand the mean levels of FSH expressed no significant changes among URSM groups as compared to first trimester pregnancies control group. A positive correlation was noticed between serum levels of TNF-alpha and the levels of LH (p < 0.05). We conclude that antioxidant enzymes (CAT, SOD), TNF-alpha, LH and FSH may play a major role in the pathogenesis of URSM. Much more work is required before the mechanisms, which lead to RSM, can be fully understood.

Protection against cisplatin-induced nephrotoxicity by Cu(II)2(3,5-diisopropylsalicylate)4.

The ability of Cu(II)(2)(3,5-diisopropylsalicylate)(4), CuDIPS, which exhibits superoxide dismutase (SOD)-like activity, to prevent cisplatin-induced nephrotoxicity was examined in rats. Rats were divided into four groups and treated as follows: (i) vehicle control; (ii) cisplatin (16 mg/kg, intraperitoneally); (iii) CuDIPS (10 mg/kg, intraperitoneally); and (iv) cisplatin plus CuDIPS. Rats were sacrificed 3 days post-treatment. Cisplatin alone resulted in significantly increased plasma creatinine and urea. Administration of 10 mg/kg CuDIPS prevented the cisplatin-induced elevation of plasma creatinine and urea and protected against kidney damage. Relative to controls, rats that received cisplatin treatment displayed a decrease of reduced glutathione (GSH) and elevated platinum and thiobarbituric acid reactive substances (TBARS) levels in the kidney. In comparison with controls, activities of antioxidant enzymes (SOD, CAT, GSH-Px and GSH-Rd) were also reduced in the kidney of rats treated with cisplatin. Administration of 10 mg/kg CuDIPS prevented cisplatin-induced alterations in renal platinum, GSH, TBARS, and antioxidant enzyme activities. This study suggests that the protection offered by CuDIPS against cisplatin-induced nephrotoxicity is partly related to maintenance of renal antioxidant systems.

Protection by metal complexes with SOD-mimetic activity against oxidative gastric injury induced by indomethacin and ethanol in rats.

We have investigated the protective effect of oral administration of copper and manganese complexes with superoxide dismutase (SOD)-mimetic activity against oxidative gastric mucosal injury induced by the non-steroidal anti-inflammatory drug indometacin with ethanol in the rat. The total area of the gastric lesions and lipid peroxidation were significantly increased 1 h after oral administration of indometacin (15 mg/kg) and ethanol, indicating an acute oxidative injury. The activities of SOD, catalase (CAT), glutathione-S-transferase (GST) and glutathione content were significantly decreased in the gastric mucosa by indometacin plus ethanol. Manganese or copper complexes showed SOD-mimetic activity. Pretreatment with these complexes protected against gastric mucosal lesions and decreased lipid peroxides, as well as attenuating the decrease in the activities of SOD, CAT and GST in gastric mucosa. These findings suggest that active oxygen species and lipid peroxidation play an important role in the pathogenesis of gastric mucosal injury induced by indometacin. In addition, we have shown that Mn and Cu complexes have gastroprotective properties against ulceration induced by indometacin plus ethanol. The present results suggest that appropriate copper or manganese complex supplementation may potentially provide prophylaxis or therapy for some pathologies associated with excessive free radical production and inhibited SOD activity.

Antitumor activities of vanadium(IV), manganese(IV), iron(III), cobalt(II) and copper(II) complexes of 2-methylaminopyridine.

The effect of Cu(II), Mn(IV), Fe(III), V(IV) and Co(II) complexes of 2-methylaminopyridine (L) having superoxide dismutase (SOD)-like activities on Ehrlich ascites carcinoma (EAC) cells was studied. Each of these complexes was intraperitoneally administered (10 mg/kg body weight for 9 days) to Swiss albino mice implanted intraperitoneally with 1 x 10(6) EAC cells. Six days after the last treatment the EAC cells were harvested using a heparinized syringe. The volume of EAC cells and EAC cell viability as well as changes in the levels of tumor cell enzyme activities of SOD, catalase, glutathione peroxidase (GSH-Px), glutathione reductase (GSH-R) and glucose-6-phosphate dehydrogenase (G6PD) were tested to examine the antitumor effects of these complexes. Both tumor volume and tumor cell viability were significantly lowered in complex-treated mice. After tumor transplantation and treatment with the complexes, the activities of GSH-Px and GSH-R were significantly lowered while SOD and G6PD activities were increased in EAC cells compared to their levels in EAC cells harvested from saline-treated mice.

A Fourier-transform infrared spectroscopic comparison of cultured human fibroblast and fibrosarcoma cells: a new method for detection of malignancies.

Infrared vibration spectroscopy appears to be a more powerful technique for tumor diagnosis than visible or UV spectroscopy. In the present work, Fourier-transform infrared (FTIR) spectroscopy was used to compare cultured normal fibroblast and fibrosarcoma cells. Significant differences were observed by comparing the spectra of the normal human cells with that of the cancer cells. The PO2 symmetric stretching mode at 1082 cm-1 is shifted to a higher frequency in the cancer cell and a broad band, whose center is located at 1064 cm-1 in the cancer cell is reduced in intensity. In addition, the decrease in intensity of the CH2 bending mode relative to that of CH3 mode is detectable only in the fibrosarcoma cell. This FTIR difference between fibroblast and fibrosarcoma cells suggests that either fatty acid chains or protein side chains of the cancer cells are partially degraded resulting in more terminal carbon (e.g., CH3). It is also possible that changes in the environment upon carcinogenesis induces a change in the relative absorption cross section for CH3 and CH2 bending vibrations. These results suggest that FTIR spectroscopy may become a promising and sensitive technique for tumor identification.