Search

Introduction: Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising approach for treating relapsed/refractory (r/r) T-cell acute lymphoblastic leukemia (T-ALL). However, it is mostly used as a bridging therapy for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, secondary allo-HSCT is costly and associated with significantly high treatment-related mortality rate than the primary transplants. In this report, we present the case of an adult T-ALL patient who underwent CD7-targeted autologous CAR-T cell therapy that was not bridged with secondary allo-HSCT. Case presentation: The adult T-ALL patient relapsed for a third time after undergoing allogeneic peripheral blood stem cell transplantation (PBSCI) and achieving the first complete remission (CR1). Therefore, the patient was administered CD7-targeted autologous CAR-T cell therapy that was not bridged with secondary allo-HSCT. Towards this, the endogenous CD7-deleted CAR (CD7-CAR7) T cells were generated using CRISPR/Cas9 gene-editing technology. However, after the first infusion, the CD7 CAR-T cells did not show significant proliferation when analyzed at two weeks and the patient became positive for peripheral measurable residual disease (MRD). Therefore, after a two-week period, an augmented dose of CAR-T cells was administered. MRD was monitored in the peripheral blood and bone marrow samples. The patient achieved complete remission and did not require targeted treatment after the completion of CD7 CAR-T-cell therapy. The current follow-up data has shown that the patient is negative for MRD and has been disease-free for more than 42 months. Conclusion: The results of this case study provide evidence for the long-term efficacy of CD7-targeted autologous CAR-T-cell therapy without requiring secondary allo-HSCT in patients with r/r T-ALL that have relapsed after previous allogeneic PBSCT. [ABSTRACT FROM AUTHOR]

In this work, we propose to employ strong optical feedback to narrow the spectral linewidth of quantum cascade lasers without using any phase control. Rate equation analysis demonstrates that optical feedback beyond a certain level always reduces the laser linewidth for any feedback phase. It is also found that the linewidth becomes less sensitive to the feedback phase for higher feedback strength. Simulations show that optical feedback with a feedback ratio of −10 dB can suppress the laser linewidth by about two orders of magnitude. This is in contrast to near-infrared laser diodes, which can be easily destabilized by strong feedback. [ABSTRACT FROM AUTHOR]

Cancer initiating cell (CIC) formation and epithelial-mesenchymal transition (EMT) are pivotal events in lung cancer cell invasion and metastasis. They have been shown to occur in gefitinib resistance. Studying the molecular mechanisms of CICs, EMT and acquired gefitinib resistance will enhance the understanding of the pathogenesis and progression of the disease and offer novel targets for effective therapies. TWIK-related acid-sensitive K(+) (TASK-1) is expressed in a subset of non-small-cell lung cancer (NSCLC) cell lines, where it promotes cell proliferation while inhibiting apoptosis. In the present study, TASK-1 was demonstrated to induce gefitinib resistance in the A549 NSCLC cell line. Overexpression of TASK-1 promoted the acquisition of CIC-like traits by A549 cells. CD133, octamer-binding transcription factor 4 (OCT-4) and Nanog have been suggested to be markers of CICs in lung cancer. It was demonstrated that overexpression of TASK-1 promoted CD133, OCT-4 and Nanog protein expression in A549 cells. Increased formation of stem cell-like populations results in EMT of cancer cells. The present study found that overexpression of TASK-1 promoted EMT of A549 cells. Thus, downregulation of TASK-1 may represent a novel strategy for EMT reversal, decreasing CIC-like traits and increasing gefitinib sensitivity of NSCLCs. [ABSTRACT FROM AUTHOR]

Background & Objective: Patients suffered from advanced endometrial cancer have poor prognosis. The five-year survival is only 25%. Histone deacetylase inhibitors have shown promise in the treatment for a variety of malignancies. In combination with traditional cytotoxic chemotherapy, histone deacetylase inhibitors can enhance the survival rate of cancer patients. This study was to investigate the effect and mechanism of trichostatin A (TSA), a histone deacetylase inhibitor, combined with paclitaxel (PTX) on the apoptosis of human endometrial carcinoma cell line Ark2., Methods: Ark2 cells were cultured in RPMI-1640 and treated with PTX alone, TSA alone or the two drugs in combination. Cell apoptosis was detected using Annexin V and Hoechst staining; perturbation of mitochondrial membrane potential was detected using MitoTracker red Poly (ADP-ribose) polymerase; caspase-9 degradation products and tubulin acetylation were detected by Western blot., Results: Results of Annexin V showed that PTX (1.5 nmol/L) plus TSA (25 nmol/L) induced a significantly higher apoptotic rate (45.2%) than PTX alone (14.1%) or TSA alone (11.2%) did in Ark2 cells after drug treatment for three days. The results of Hoechst staining and Annexin V were consistent. A loss of mitochondrial membrane potential could activate the apoptotic cascade. Cleavages of PARP and caspase-9 were significantly apparent in PTX plus TSA group than in PTX group or TSA group (P<0.05). PTX and TSA could induce tubulin acetylation. PTX in combination with TSA increased acetylated tublins and microtubule stability compared with either drug alone. The loss of mitochondrial membrane potential was more dramatic in the drug combination group than the single drug group. The effects of TSA and PTX were synergistic (q=2.54)., Conclusion: TSA and PTX could induce apoptosis of Ark2 cells, which may be through the loss of mitochondrial membrane potential and acetylation of non-histone proteins induced by histone deacetylase inhibitors.