METHODS: We carried a review of medical records of breast and lung cancer patients hospitalized in years 2003 and 2009 at Penang General Hospital, a public tertiary care center in Penang Island, north of Malaysia. Patients with hypercalcemia (defined as a calcium level above 10.5 mg/dl) at the time of cancer diagnosis or during cancer treatment had their medical history abstracted, including presence of metastasis, chemotherapy types and doses, calcium levels throughout cancer treatment, and other co-morbidity. The mean calcium levels at first hospitalization before chemotherapy were compared with calcium levels at the end of or at the latest chemotherapy treatment. Statistical analysis was conducted using the Chi-square test for categorical data, logistic regression test for categorical variables, and Spearman correlation test, linear regression and the paired sample t tests for continuous data.
RESULTS: Of a total 1,023 of breast cancer and 814 lung cancer patients identified, 292 had hypercalcemia at first hospitalization or during cancer treatment (174 breast and 118 lung cancer patients). About a quarter of these patients had advanced stage cancers: 26.4% had mild hypercalcemia (10.5-11.9 mg/dl), 55.5% had moderate (12-12.9 mg/dl), and 18.2% severe hypercalcemia (13-13.9; 14-16 mg/dl). Chemotherapy lowered calcium levels significantly both in breast and lung cancer patients with hypercalcemia; in particular with chemotherapy type 5-flurouracil+epirubicin+cyclophosphamide (FEC) for breast cancer, and gemcitabine+cisplatin in lung cancer.
CONCLUSION: Chemotherapy decreases calcium levels in breast and lung cancer cases with hypercalcemia at cancer diagnosis, probably by reducing PTHrP levels.
OBJECTIVE: This study investigates the chemical constituents, anti-proliferative, and apoptotic properties of C. nutans root extracts.
MATERIALS AND METHODS: The roots were subjected to solvent extraction using methanol and ethyl acetate. The anti-proliferative effects of root extracts were tested at the concentrations of 10 to 50 μg/mL on MCF-7 and HeLa by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay for 72 h. Morphological changes were observed under light microscope. Pro-apoptotic effects of root extracts were examined using flow cytometric analysis and RT-PCR. The chemical compositions of root extracts were detected using GC-MS.
RESULTS: The proliferation of MCF-7 cells was inhibited with the IC50 values of 35 and 30 μg/mL, respectively, for methanol and ethyl acetate root extracts. The average inhibition of HeLa cells was ∼25%. Induction of apoptosis in MCF-7 was supported by chromatin condensation, down-regulation of BCL2 and unaltered expression of BAX. However, only ethyl acetate extract caused the loss of mitochondrial membrane potential. GC-MS analysis revealed the roots extracts were rich with terpenoids and phytosterols.
DISCUSSION AND CONCLUSIONS: The results demonstrated that root extracts promote apoptosis by suppressing BCL2 via mitochondria-dependent or independent manner. The identified compounds might work solely or cooperatively in regulating apoptosis. However, further studies are required to address this.
METHODS: Molecular docking and molecular dynamics simulations were used for EGFR, p38, ERK1/2, and AKT. The effects of berberine and lapatinib on MAPK and PI3K pathways in MDA-MB231 and MCF-7 cells were evaluated using immunoflorescence assays, and the amounts of phosphorylated kinases were compared to total kinases after treating with different concentrations of berberine.
RESULTS: Simulations showed berberine accurately interacted with EGFR, AKT, P38, and ERK1/2 active sites in silico (scores = -7.57 to -7.92 Kcal/mol) and decreased the levels of active forms of corresponding enzymes in both cell lines; however, berberine binding to p38 showed less stability. Cytotoxicity analysis indicated that MDA-MB231 cells were resistant to berberine compared to MCF-7 cells [72 h IC50 = 50 versus 15 μM, respectively). Also, lapatinib strongly activated AKT but suppressed EGFR in MDA-MB231 cells. The activity of EGFR, AKT, P38, and ERK1/2 were affected by berberine; however, berberine dramatically reduced EGFR and AKT phosphorylation.
CONCLUSION: By way of its multikinase inhibitory effects, berberine might be a useful replacement for lapatinib, an EGFR inhibitor which can cause acquired drug resistance in patients.
METHODS: MCF-7 and MDA-MB231 cells were treated with several concentrations of FKA. The apoptotic analysis was done through the MTT assay, BrdU assay, Annexin V analysis, cell cycle analysis, JC-1 mitochondrial dye, AO/PI dual staining, caspase 8/9 fluorometric assay, quantitative real time PCR and western blot. For the metastatic assays, the in vitro scratch assay, trans-well migration/invasion assay, HUVEC tube formation assay, ex vivo rat aortic ring assay, quantitative real time PCR and western blot were employed.
RESULTS: We have investigated the effects of FKA on the apoptotic and metastatic process in two breast cancer cell lines. FKA induces apoptosis in both MCF-7 and MDA-MB231 in a dose dependent manner through the intrinsic mitochondrial pathway. Additionally, FKA selectively induces a G2/M arrest in the cell cycle machinery of MDA-MB231 and G1 arrest in MCF-7. This suggests that FKA's anti-cancer activity is dependent on the p53 status. Moreover, FKA also halted the migration and invasion process in MDA-MB231. The similar effects can be seen in the inhibition of the angiogenesis process as well.
CONCLUSIONS: FKA managed to induce apoptosis and inhibit the metastatic process in two breast cancer cell lines, in vitro. Overall, FKA may serve as a promising candidate in the search of a new anti-cancer drug especially in halting the metastatic process but further in vivo evidence is needed.
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.
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.