Anthracyclines are the most widely used anticancer agents for breast cancer, of which doxorubicin and epirubicin have been reported to have equal efficacy. Unfortunately, the integrity of the immune system of breast cancer patients is severely affected by chemotherapy. This study compared the effect of combination chemotherapy with epirubicin (5-fluorouracil, epirubicin, cyclophosphamide (FEC)) and doxorubicin (5-fluorouracil, doxorubicin, cyclophosphamide (FDC)) regimens on subsets of the immune cells of patients with primary malignant breast tumors. Our aim was to determine the best regimen that produces the least degree of myelosuppression. Blood from 80 breast cancer patients undergoing chemotherapy (40 FEC and 40 FDC) was taken before chemotherapy and after every cycle (3 weeks) for 6 cycles. Blood was also taken from 40 normal healthy donors who served as normal control. Subsets of lymphocytes T-helper cells (CD3(+)CD4(+)), T-cytotoxic cells (CD3(+) CD8(+)), B-cells (CD19(+) CD20(+)) and NK cells (CD16(+)/CD56(+)CD3(-)) were analyzed by flow cytometry (FacsCalibur, BD) using monoclonal antibodies (Multitest, BD). All patients in the FEC and FDC groups suffered from myelosuppressive side effects. Both regimens led to an increase in the counts of monocytes but decreased polymorphonuclear cells (PMNs) and lymphocytes. Percentages of T-cytotoxic cells and NK cells were increased, but the percentage of B-cells was dramatically decreased. The phagocytic and intracellular killing ability of PMNs were also suppressed (p<0.01). No significant difference was found between the epirubicin-based regimen and doxorubicin-based regimen with regard to numbers of immune cells, percentages of lymphocytes subsets, Th/CTL ratio, engulfment and killing abilities of PMNs. In conclusion, we found that the epirubicin-based regimen is not superior to the doxorubicin-based regimen with respect to their toxicity of the immune cells, Th/CTL ratio and PMN count and functions. Moreover, both FEC and FDC regimens appear to conserve the cell-mediated immunity response needed for fighting against cancer cells.
Of the twenty microorganisms screened for metabolism of goniothalamin only Streptomyces aurofaciens ATCC 10762 and Nocardia species NRRL 5646 produced two metabolites, 3,4-dihydrogoniothalamin and 3,4,7,8 tetrahydrogoniothalamin. The identity of the isolated metabolites were established using TLC, HPLC, MS, IR, and 1H- and 13C-NMR spectroscopy. In addition, the substrate had been transformed into two unknown metabolites by Aspergillus niger ATCC 11394 and Septomyxa affinis ATCC 6737 in low yield. Three of the metabolites were also detected and identified in the urine and blood samples of the goniothalamin-treated Sprague-Dawley rats. The obtained results are in agreement with and support the principle of microbial models of mammalian metabolism.
Erythroxylum cuneatum (E. cuneatum) which belongs to Erythroxylaceae family is a tropical flowering plant from the genus of Erythroxylum. It is used in Malaysia and Thailand's traditional medicines, yet there is limited scientific reports on its medicinal value. This study aimed at exploring the antioxidative and anti-inflammatory properties of E. cuneatum alkaloid leaf extract. The alkaloid extract was obtained through Soxhlet heat extraction method, while the antioxidantive properties were assessed via 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, ferric reducing antioxidant power (FRAP) and xanthine oxidase inhibition (XOI) assays. Further, anti-inflammatory property of the extract was evaluated on rat's model of carrageenan induced paw model of edema via physical measurements and histology. The extract exhibited antioxidant activity with an EC50 value of 1482 μg/ml in the DPPH radical scavenging assay, an EC1 value of 2191 μg/ml in the FRAP assay and 10.15 ± 6.20% in the XOI assay. Rats pretreated with the extract have shown dose dependent decrease in paw edema when compared to non-treated group of rats. The highest dose (50 mg/kg) of extract exhibited similar effects to aspirin in terms of reducing paw thickness, leucocytes infiltration and disruption of collagen. In conclusion, the E. cuneatum alkaloid leaf extract possesses both antioxidative and anti-inflammatory properties suggesting its potentials for future development of antioxidant and anti-inflammatory drugs.