METHOD: TQ-nanoparticles were prepared and optimized by using two different formulations with different drugs to PLGA-PEG ratio (1:20 and 1:7) and different PLGA-PEG to Pluronic F68 ratio (10:1 and 2:1). The morphology and size were determined using TEM and DLS. Characterization of particles was done using UV-VIS, ATR-IR, entrapment efficiency, and drug release. The effects of drug, polymer, and surfactants were compared between the two formulations. Cytotoxicity assay was performed using MTS assay.
RESULTS: TEM finding showed 96% of particles produced with 1:7 drug to PLGA-PEG were less than 90 nm in size and spherical in shape. This was confirmed with DLS which showed smaller particle size than those formed with 1:20 drug to PLGA-PEG ratio. Further analysis showed zeta potential was negatively charged which could facilitate cellular uptake as reported previously. In addition, PDI value was less than 0.1 in both formulations indicating monodispersed and less broad in size distribution. The absorption peak of PLGA-PEG-TQ-Nps was at 255 nm. The 1:7 drug to polymer formulation was selected for further analysis where the entrapment efficiency was 79.9% and in vitro drug release showed a maximum release of TQ of 50%. Cytotoxicity result showed IC50 of TQ-nanoparticle at 20.05 μM and free TQ was 8.25 μM.
CONCLUSION: This study showed that nanoparticle synthesized with 1:7 drug to PLGA-PEG ratio and 2:1 PLGA-PEG to Pluronic F68 formed nanoparticles with less than 100 nm and had spherical shape as confirmed with DLS. This could facilitate its transportation and absorption to reach its target. There was conserved TQ stability as exhibited slow release of this volatile oil. The TQ-nanoparticles showed selective cytotoxic effect toward UACC 732 cells compared to MCF-7 breast cancer cells.
MATERIALS AND METHODS: In hepatoprotective activity, liver damage was induced by treating rats with 1.0 mL carbon tetrachloride (CCl4)/kg and MEA extract was administered at a dose of 50, 250 and 500 mg/kg 24 h before intoxication with CCl4. Cytotoxicity study was performed on MCF-7 (human breast cancer), DBTRG (human glioblastoma), PC-3 (human prostate cancer) and U2OS (human osteosarcoma) cell lines. 1H, 13C-NMR (nuclear magnetic resonance), and IR (infrared) spectral analyses were also conducted for MEA extract.
RESULTS: In hepatoprotective activity evaluation, MEA extract at a higher dose level of 500 mg/kg showed significant (p<0.05) potency. In cytotoxicity study, MEA extract was more toxic towards MCF-7 and DBTRG cell lines causing 78.7% and 64.3% cell death, respectively. MEA extract in 1H, 13C-NMR, and IR spectra exhibited bands, signals and J (coupling constant) values representing aromatic/phenolic constituents.
CONCLUSIONS: From the results, it could be concluded that MEA extract has potency to inhibit hepatotoxicity and MCF-7 and DBTRG cancer cell lines which might be due to the phenolic compounds depicted from NMR and IR spectra.
MATERIALS AND METHODS: MCF-7 cells were plated at a density of 15105 cells/well in 6-well plates. After 24h, cells were treated with a series of concentrations of rapamycin while only adding DMEM medium with PEG for the control regiment and grown at 37oC, 5% CO2 and 95% air for 72h. Trypan blue was used to determine the cell viability and proliferation. Untreated and rapamycin-treated MCF-7 cells were also examined for morphological changes with an inverted-phase contrast microscope. Alteration in cell morphology was ascertained, along with a stage in the cell cycle and proliferation. In addition, cytotoxicity testing was performed using normal mouse breast mammary pads.
RESULTS: Our results clearly showed that rapamycin exhibited inhibitory activity on MCF-7 cell lines. The IC50 value of rapamycin on the MCF-7 cells was determined as 0.4μg/ml (p<0.05). Direct observation by inverted microscopy demonstrated that the MCF-7 cells treated with rapamycin showed characteristic features of apoptosis including cell shrinkage, vascularization and autophagy. Cells underwent early apoptosis up to 24% after 72h. Analysis of the cell cycle showed an increase in the G0G1 phase cell population and a corresponding decrease in the S and G2M phase populations, from 81.5% to 91.3% and 17.3% to 7.9%, respectively.
CONCLUSIONS: This study demonstrated that rapamycin may potentially act as an anti-cancer agent via the inhibition of growth with some morphological changes of the MCF-7 cancer cells, arrest cell cycle progression at G0/G1 phase and induction of apoptosis in late stage of apoptosis. Further studies are needed to further characterize the mode of action of rapamycin as an anti-cancer agent.
MATERIALS AND METHODS: Patients who were treated with first line palliative chemotherapy for de novo MBC from 2002-2011 in UMMC were identified from the UMMC Breast Cancer Registry. Information collected included patient demographics, histopathological features, treatment received, including the different chemotherapy regimens, and presence of FN and TRD. FN was defined as an oral temperature >38.5° or two consecutive readings of >38.0° for 2 hours and an absolute neutrophil count <0.5x109/L, or expected to fall below 0.5x109/L (de Naurois et al, 2010). TRD was defined as death occurring during or within 30 days of the last chemotherapy treatment, as a consequence of the chemotherapy treatment. Statistical analysis was performed using the SPSS version 18.0 software. Survival probabilities were estimated using the Kaplan-Meier method and differences in survival compared using log-rank test.
RESULTS: Between 1st January 2002 and 31st December 2011, 424 patients with MBC were treated in UMMC. A total of 186 out of 221 patients with de novo MBC who received first line palliative chemotherapy were analyzed. The mean age of patients in this study was 49.5 years (range 24 to 74 years). Biologically, ER status was negative in 54.4% of patients and Her-2 status was positive in 31.1%. A 5-flourouracil, epirubicin and cyclophosphamide (FEC) chemotherapy regimen was chosen for 86.6% of the cases. Most patients had multiple metastatic sites (58.6%). The main result of this study showed a FN rate of 5.9% and TRD rate of 3.2%. The median survival (MS) for the entire cohort was 19 months. For those with multiple metastatic sites, liver only, lung only, bone only and brain only metastatic sites, the MS was 18, 24, 19, 24 and 8 months respectively (p-value= 0.319).
CONCLUSIONS: In conclusion, we surmise that FEC is a safe regimen with acceptable FN and TRD rates for de novo MBC.
MATERIALS AND METHODS: This study aimed to assess the effects of commercial and recombinant bromelain on the cytokinetic behavior of MCF-7 breast cancer cells and their potential as therapeutic alternatives in cancer treatment. Cytotoxic activities of commercial and recombinant bromelain were determined using (sulforhodamine) SRB assay. Next, cell viability assays were conducted to determine effects of commercial and recombinant bromelain on MCF-7 cell cytokinetic behavior. Finally, the established growth kinetic data were used to modify a model that predicts the effects of commercial and recombinant bromelain on MCF-7 cells.
RESULTS: Commercial and recombinant bromelain exerted strong effects towards decreasing the cell viability of MCF-7 cells with IC50 values of 5.13 μg/mL and 6.25 μg/mL, respectively, compared to taxol with an IC50 value of 0.063 μg/mL. The present results indicate that commercial and recombinant bromelain both have anti-proliferative activity, reduced the number of cell generations from 3.92 to 2.81 for commercial bromelain and to 2.86 for recombinant bromelain, while with taxol reduction was to 3.12. Microscopic observation of bromelain-treated MCF-7 cells demonstrated detachment. Inhibition activity was verified with growth rates decreased dynamically from 0.009 h-1 to 0.0059 h-1 for commercial bromelain and to 0.0063 h-1 for recombinant bromelain.
CONCLUSIONS: Commercial and recombinant bromelain both affect cytokinetics of MCF-7 cells by decreasing cell viability, demonstrating similar strength to taxol.
METHODS AND MATERIALS: Patients with T3-4, N2 M0 breast cancer diagnosed between January 2005 and December 2008 and who received at least one cycle of neoadjuvant chemotherapy were eligible for this study. Thirty-four patients were identified from the Chemotherapy Daycare Records and their medical records were reviewed retrospectively. The neoadjuvant chemotherapy regimen administered was at the discretion of the treating oncologist. Breast tumour size and nodal status was assessed at diagnosis, at each cycle and before surgery.
RESULTS: All 34 patients had invasive ductal cancer. The median age was 52 years (range 27-69). 65% had T4 disease and 76% were clinically lymph node positive at diagnosis. The median size of the breast tumour at presentation was 80 mm (range 42-200 mm). Estrogen and progesterone receptor positivity was seen in less than 40% and HER2 positivity, by immunohistochemistry, in 27%. The majority (85%) of patients had anthracycline based chemotherapy, without taxanes. The overall response rate (clinical CR+PR) was 67.6% and pathological complete responses were apparent in two (5.9%). 17.6% of patients defaulted part of their planned treatment. Recurrent disease was seen in 44.1% and the median time to relapse was 11.3 months. The three year disease free and overall survival rates were 52.5% and 58% respectively.
CONCLUSION: Neoadjuvant chemotherapy for locally advanced breast cancer in a Malaysian setting confers response and pCR rates comparable to published clinical trials. Patients undergoing neoadjuvant chemotherapy are at risk of defaulting part of their treatment and therefore their concerns need to be identified proactively and addressed in order to improve outcomes.