Breast cancer is one of the most abundant forms of cancer among the women and men worldwide. The common phenotypic abnormality of breast cancer cells is due to the dysregulation of cell cycle control. The breast cancer genes includes; BRCA-1, BRCA-2 and P53. The relative incident rate of breast cancer in Asian countries is low than the Non-Asian/ western countries. However, the rate is increasing at a more rapid rate in Asian countries. The increasing incidence rate in West indicates many factors including childbirth trends, age, diet plans and nulliparity.
Objectives: Novel treatments improved survival in patients with advanced melanoma in clinical trials. We assessed real-world outcomes of novel treatments in The Netherlands. MethOds: Data were retrieved from the Dutch Melanoma Treatment Registry (DMTR) for patients diagnosed with advanced melanoma between July 2012 and April 2016 (data cut-off March 20, 2016). The DMTR prospectively records detailed data on all Dutch unresectable stage IIIc/IV melanoma patients. Descriptive statistics and Kaplan-Meier estimates were used to assess real-world outcomes. Results: A total of 1673 patients received novel treatments in Dutch real-world practice. Most of the patients were male (59%) and the median age was 61. The most frequently prescribed treatment in the first line was vemurafenib (37%), followed by ipilimumab (46%) in the second line and trial-based treatments (19%) in the third line or higher. Median follow-up was 17.9 months (IQR: 9.0-27.0). The median time to next treatment was 4.9 (IQR: 2.8-8.9), 4.5 (IQR: 2.6-8.4) and 4.2 (IQR: 2.4-8.2) months from the first, second and third line, respectively. Median overall survival (OS) was 10 months (IQR: 4.9-21.8); one-and two-year survival rates were 43% and 23%, respectively. Patients with elevated LDH (n= 569; 34%), M1c disease (n= 1308; 78%) and brain metastases (n= 433; 26%) had significantly lower survival outcomes (median OS: 5.7 (p< 0.001), 6.9 (p< 0.001) and 8.1 (p< 0.001) months, respectively). A total of 485 patients (29%) experienced at least one grade 3/4 adverse event and 241 patients (50%) early discontinued treatment due to a treatment-related toxicity. The most commonly reported adverse events were colitis (n= 116; 24%) and skin toxicity (n= 104; 21%); one treatment-related death was reported. cOnclusiOns: Novel treatments improved survival in patients with advanced melanoma in Dutch real-world practice. Patients with elevated LDH, M1c disease and brain metastases had worse survival outcomes. Of all patients with severe adverse events, 50% early discontinued treatment but only one treatment-related death occurred.
48PMedical Research Society concentrations (e.g 30 nM) SN38 induced p53, p21, Bax and Bcl-XI. The Bax:Bcl-xl ratio changed Little. Prior Bcl-XI ko enhanced the global effect of SN38 on HCTI 16 wt cells (surviving fraction of cell counts relative to treated controls -SN38 alone 23%+/-2%, SN38 following Bcl-XI ko 12% +/-3%. day 3, n=3, ~4 . 0 1 ) . Prior Bcl-XI ko also produced a qualirarive shift in cellular response. The major response in HCT116 wt cells to SN38 alone is a prolonged growth arrest with features of drug-induced senescence, but little apoptosis. Prior Bcl-XI ko resulted in an apoptotic response (cleaved Parp fractionuntreated controls 2% +/-0.22, after SN38 alone 4%+/-1%. after SN38 following Bcl-XI ko 25% +/-5%. day 3, n=5, p
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