RESUMEN
ABL tyrosine kinase inhibitors (TKIs) act an irreplaceable role in the management of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). The treatment of these diseases has been revolutionized by the application of immunotherapeutic modalities. However, diseases with ABL kinase domain mutation T315I are resistant to the majority of TKIs, which is responsible for treatment failure. Olverembatinib is a third-generation TKI that has been approved for the treatment of T315I-mutated chronic myeloid leukemia (CML) in China; its usage in Ph+ ALL needs further exploration. Here, we present two cases with relapsed T315I mutation Ph+ ALL who received the combination regimen of blinatumomab and olverembatinib. This regimen, which has not been reported yet, was safe and effective as the patients achieved minimal residual disease (MRD) negative after 1 cycle of therapy. The management of these cases provides evidence of this new chemo-free regimen as an efficient approach for relapsed or refractory(R/R)Ph+ ALL.
Asunto(s)
Alquinos , Anticuerpos Biespecíficos , Benzamidas , Cromosoma Filadelfia , Piperidinas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Pirazoles , Piridinas , Humanos , Resistencia a Antineoplásicos/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas de Fusión bcr-abl/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , MutaciónRESUMEN
The efficient, safe and eco-friendly disposal of the chromium-containing sludge (CCS) has attracted an increasing concern. In this study, Co-processing of CCS was developed via employing sintering and ironmaking combined technology for its harmless disposal and resource utilization. Crystalline phase and valence state transformation of chromium (Cr), technical feasibility assessment, leaching risk, characteristics of sintered products, and pollutant release during CCS co-processing were investigated through a series of laboratory-scale sintering pot experiments and large scale industrial trials. The results showed that the content of Cr(VI) in sintered products first increased then decreased with increasing temperature ranges of 300 °C-800 °C, and reached a maximum of 2189.64 mg/kg at 500 °C. 99.99% of Cr(VI) can be reduced to Cr(III) at above 1000 °C, which was attributed to the transformation of the Cr(VI)-containing crystalline phases (such as, MgCrO4 and CaCrO4) to the (Mg, Fe2+)(Cr, Al, Fe3+)2O4. The industrial trial results showed that adding 0.5 wt CCS to sintering feed did not have adverse effects on the properties of the sintered ore and the plant's operating stability. The tumbler index of sinter was above 78% and the leaching concentrations of TCr (0.069 mg/L) was significantly lower than the Chinese National Standard of 1.0 mg/L (GB5085.3-2007). The TCr contents of sintering dust and blast furnace gas (BFG) scrubbing water were less than 0.19 wt and 0.11 mg/L, respectively, which was far below the regulatory limit (1.5 mg/L, GB13456-2012). The mass balance evaluation results indicated that at least 89.9% of the Cr in the CCS migrated into the molten iron in the blast furnace (BF), which became a useful supplement to the molten iron. This study provided a new perspective strategy for the safe disposal and resource utilization of CCS in iron and steel industry.
Asunto(s)
Cromo , Aguas del Alcantarillado , Cromo/química , Aguas del Alcantarillado/química , Hierro/químicaRESUMEN
OBJECTION: Immunotherapy based on T cells is a new therapy for Acute myeloid leukemia (AML). However, there has not been considerable improvement compared with traditional chemotherapeutics. This study aimed to identify important immune cells, genes, and drugs associated with the immunotherapy of AML. METHODS: The gene expression profile and clinical data of patients with AML were downloaded from TCGA database, and the abundance ratio of immune cells was obtained via CIBERSORT. Kaplan-Meier (KM) survival analysis was used to assess the relationship between immune cells and survival time of patients with AML. Differentially expressed genes (DEGs) analysis was conducted to obtained DEGs related to mast cells. Then, protein-protein interaction (PPI) analysis and enrichment analysis were performed to explore the hub genes. Finally, Connectivity Map (CMap) database was utilized to predicts potential drugs that may reverse or induce the mast cell-related gene expression. RESULTS: Our study showed that mast cell was correlated with survival time of patients with AML, and 135 genes were screened to be related with mast cells. 6 hub genes were identified via PPI network, and 3 potential small molecule drugs were screened to be related to regulating the mast cell-related gene expression via CMap database. CONCLUSION: The hub genes and drugs have high research value and clinical application in AML therapy. Our study not only provides gene targets and small molecule drugs for AML immunotherapy concerning mast cells but also provides new ideas for researchers to explore immunotherapy targets of other tumors.
Asunto(s)
Antineoplásicos/farmacología , Leucemia Mieloide Aguda/tratamiento farmacológico , Mastocitos/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/farmacología , Antineoplásicos/química , Descubrimiento de Drogas , Perfilación de la Expresión Génica , Humanos , Inmunoterapia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/inmunología , Mastocitos/inmunología , Mastocitos/metabolismo , Terapia Molecular Dirigida , Bibliotecas de Moléculas Pequeñas/química , Transcriptoma/efectos de los fármacosRESUMEN
Electro-deposition is a smart, safe and efficient method for biomaterial manufacturing. Collagen, a functional protein with excellent biocompatibility and biosafety, is a promising candidate for tissue engineering and biomedical applications. However, there are few reports on electro-deposition of biomaterials using collagen without electrically or magnetically active nanoparticles. In this study, electro-deposition was employed to swiftly fabricate tube-like collagen-chitosan hydrogels in a mild environment. Fourier transform infrared spectroscopy was employed to analyze the ingredients of the tube-like hydrogels. The result showed that the hydrogels contained both collagen and chitosan. The distribution and content of collagen in the hydrogels was further measured by hematoxylin-eosin staining and hydroxyproline titration. Collagen was distributed homogeneously and its content was related to the initial collagen:chitosan ratio. The tension resistance of the composite gels and the thermal stability of collagen in the composites were obviously enhanced by the chitosan doping. Meanwhile, the tube-like hydrogels retained a good ability to promote cell proliferation of collagen. This method offers a convenient approach to the design and fabrication of collagen-based materials, which could effectively retain the bioactivity and biosafety of collagen and furnish a new way to enhance the stability of collagen and the tensile strength of collagen-based materials.