Showing papers in "International Journal of Hematology and Oncology in 2020"
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TL;DR: This study is one of the rare multicentric real-life data showing the efficacy and tolerability of the FLOT regimen in the perioperative treatment in GC and EJC.
Abstract: In patients with gastic cancer, five-year survival is poor in the locally advanced stage. Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) combination regimen has been shown to provide a survival advantage in the locally advanced stage. In this study, we aimed to evaluate the efficacy and tolerability of FLOT with real-life data in patients with locally advanced gastric/esophagogastric junction cancers. This retrospective study was conducted between June 2016 March 2020 and included 106 patients’ data from six centers in Turkey. Median age was 60 (33-82). Primary tumor localization was stomach in 76 (71.7%) patients. Seventy-six (71.7%) patients were operated after median 4 (1-8 cycles) cycles of preoperative FLOT. Pathological complete regression (pCR)was obtained in 10 (13.1%) of the operated patients. Median follow-up was 9.1 (1.4-45.7) months. One-year DFS was 63.2% and the two-year OS was 65.1%. Three (2.8%) patients had chemotherapy-related deaths. Due to chemotherapy-related toxicity and intoleration, 19 (17.9%) patients had dose reduction. The pCR obtained by FLOT appears higher than other regimens. This study is one of the rare multicentric real-life data showing the efficacy and tolerability of the FLOT regimen in the perioperative treatment in GC and EJC.
TL;DR: It is suggested that ATRA-induced granulocytic differentiation is inhibited in NOL7-downregulated NB4 cells and loss of Nol7 might be involved in the development of ATRA resistance.
Abstract: The promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) fusion gene is present in 98% of the patients with acute promyelocytic leukemia (APL), the M3 subtype of acute myeloid leukemia (AML). All-trans retinoic acid (ATRA) is widely used to treat patients with APL. Nucleolar Protein 7 (NOL7) is a tumor suppressor gene regulated by retinoid X receptor (RXR). The 6p23 chromosomal region, where NOL7 is located, is associated with many cancers, including AML. Here, we aimed to investigate the effect of NOL7 in two AML cell lines (the PML-RARA-positive NB4 cell line and the PML-RARA-negative HL60 cell line) and in the resistance to ATRA. For this purpose, we knocked down NOL7 expression by using short interfering RNA (siRNA) and stimulated the cells with ATRA. Apoptosis, cell viability, proliferation, and granulocytic differentiation analyses were performed. Our findings show that granulocytic differentiation was blocked in ATRA-treated NB4 cells 24 hours after NOL7 siRNA transfection when the expression of NOL7 had been reduced by 81%. Downregulation of NOL7 had no apparent effect on the cellular proliferation and apoptosis. Our study suggests that ATRA-induced granulocytic differentiation is inhibited in NOL7-downregulated NB4 cells. These results suggest that NOL7 expression contributes to ATRA-induced granulocytic differentiation and loss of NOL7 might be involved in the development of ATRA resistance.
TL;DR: In the patients with RAS wild type tumours, CT and anti-EGFR combination was reasonable approach for first line treatment and BRAF mutation, irrespective of CT regimen, was associated with poor survival and more common in RCC patients.
Abstract: RAS and BRAF mutation and primary tumour sideness are prognostic and predictive factors in metastatic colorectal cancer (mCRC). We aimed to investigate RAS-BRAF mutation rates and responses to biologic agents the effects of tumour sideness on survival. This was a retrospective study conducted at three Turkish institutes. 303 patients with mCRC who were examined for tumour RAS and 172 examined for tumour BRAF mutations between 2006-2018. A total of 303 (M/F= 186/117) patients were included to study. Median age was 63 (range: 23-86) years. Median follow-up was 22.8 (range: 19.1-26.4) months. In the RAS wild type population; ad- dition to anti-EGFR agents to standard chemotherapy (CT) had better outcomes than Bevacizumab+CT. Median PFS was improved with anti-EGFR agents (Respectively PFS; 14.5 months, 8.7 months) (log rank p= 0.007 HR= 0.59). Median OS was similar between CT+anti-EGFR and CT+Bevacizumab arms (Respectively OS; 29.3 months, 21.7 months) (log rank p= 0.418; HR= 0.75). RAS muta- tion rates were similar between right colon cancer (RCC) and left colon cancer (LCC), BRAF mutation rates were significantly increased in RCC (22.2 vs 2.7%, p< 0.0001). RCC (24.1%) had worse prognosis than LCC (75.9%). However, this difference was not significant (PFS: 10.4 vs 10.0 months (log rank p= 0.136) , OS: 21.5 vs 23.1 months (log rank p= 0.436). We concluded that in the patients with RAS wild type tumours, CT and anti-EGFR combination was reasonable approach for first line treatment. BRAF mutation, irrespective of CT regimen, was associated with poor survival and more common in RCC patients. Keywords: Metastatic colorectal cancer, RAS and BRAF, Sidedness, Prognosis