Cancer medicine
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The main aim of this study is to investigate whether baseline lactate dehydrogenase (LDH) is associated with the clinical outcome of non small-cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). We searched Pubmed, the Cochrane Central library and Embase for peripheral blood biomarker of LDH in advanced NSCLC patients treated with ICIs. We extracted the hazard ratio (HR) with 95% confidence interval (CI) for the progression free survival (PFS) and overall survival (OS) and performed meta-analysis of HR. ⋯ The association remained significant in the multivariate analysis that elevated pretreatment LDH level was associated with poor PFS (HR = 1.62, 95% CI 1.26-2.08, P < 0.001) and OS (HR = 2.38, 95% CI 1.37-4.12, P = 0.002). A high pretreatment LDH level was significantly correlated with shorter PFS and OS. Pretreatment LDH may serve as a predictive biomarker for advanced NSCLC patients treated with ICIs.
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Methods to deepen clinical responses to ibrutinib are needed to improve outcomes for patients with chronic lymphocytic leukemia (CLL). This study aimed to determine the safety and efficacy of combining a janus kinase (JAK)-inhibitor with ibrutinib because JAK-mediated cytokine-signals support CLL cells and may not be inhibited by ibrutinib. The JAK1/2 inhibitor ruxolitinib was prescribed to 12 CLL patients with abnormal serum beta-2 microglobulin levels after 6 months or persistent lymphadenopathy or splenomegaly after 12 months on ibrutinib using a 3 + 3 phase 1 trial design (NCT02912754). ⋯ The combination was well-tolerated without dose-limiting toxicities. Cyclic changes in platelets, lymphocytes, and associated chemokines and thrombopoietic factors were observed and partial response criteria were met in 2 of 12 patients. The results suggest that JAK-signaling helps CLL cells persist in the presence of ibrutinib and ruxolitinib with ibrutinib is well-tolerated and may be a useful regiment to use in combination therapies for CLL.
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Evaluation of the efficacy of adeno-associated virus 2 mediated gene transfer of vascular endothelial growth factor Trap (AAV2-VEGF-Trap) alone or combination with paclitaxel in a mouse model of triple-negative breast cancer (TNBC) using diffusion-weighted magnetic resonance imaging (DW-MRI) and in vivo fluorescence imaging. ⋯ AAV2-VEGF-Trap inhibits TNBC growth though inhibiting tumor neovascularization with a single intravenous injection, and AAV2-VEGF-Trap exhibits a synergistic effect when used in combination with paclitaxel for TNBC neoadjuvant therapy. In vivo fluorescence imaging can detect the anti-angiogenesis effect of AAV2-VEGF-Trap early and noninvasively. DW-MRI can longitudinally monitor the neoadjuvant efficacy of TNBC.
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The long-term effects of tyrosine kinase inhibitors (TKIs), including imatinib, and surgical intervention on advanced gastrointestinal stromal tumor (GIST) were evaluated. All 379 patients had metastatic or recurrent GIST and started 400 mg/d imatinib at the Asan Medical Center in periods 1 and 2 [2001-2007 (33.2%) and 2008-2014 (66.8%), respectively]. Men constituted 60.4%; median patient age and tumor size at the initiation of imatinib were 58.6 (14.6-85.5) years and 51 (0-324) mm, respectively, without differences between periods except for older age and less preimatinib surgery in period 2. ⋯ PFS with imatinib (P = 0.002) and OS (P = 0.019) were significantly longer in period 2. Young age, smaller tumor size at the initiation of imatinib, KIT exon 11 mutation, surgical intervention, and period 2 were favorable factors for PFS and OS. Patients with advanced GIST showed better prognosis with the optimal use of imatinib, along with active surgical intervention and more common use of subsequent TKIs in period 2.
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Increasing evidence revealed that ten-eleven translocation 1 (TET1) plays an important role in tumorigenesis and chemoresistance, but its functions in gemcitabine resistance in cholangiocarcinoma (CCA) remain unknown. This study aims to investigate the effect of TET1 on gemcitabine resistance in CCA and the possible effect on P-glycoprotein (P-gp) expression encoded by multidrug resistance (MDR) genes. We established two kinds of gemcitabine-resistant CCA cell lines and confirmed its specific features. ⋯ Additionally, Kaplan-Meier survival and the log-rank test showed that decreased expression of TET1 was associated with poorer prognosis of CCA patients with chemotherapy. These findings suggest that TET1 expression reverses gemcitabine resistance in CCA accompanied by a reduction in P-gp expression. Thus, TET1 may be a promising target to overcome chemoresistance in CCA.