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1.
Molecules ; 29(17)2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39274845

ABSTRACT

Artificial photocatalytic energy conversion is a very interesting strategy to solve energy crises and environmental problems by directly collecting solar energy, but low photocatalytic conversion efficiency is a bottleneck that restricts the practical application of photocatalytic reactions. The key issue is that the photo-generated charge separation process spans a huge spatio-temporal scale from femtoseconds to seconds, and involves complex physical processes from microscopic atoms to macroscopic materials. Femtosecond transient absorption (fs-TA) spectroscopy is a powerful tool for studying electron transfer paths in photogenerated carrier dynamics of photocatalysts. By extracting the attenuation characteristics of the spectra, the quenching path and lifetimes of carriers can be simulated on femtosecond and picosecond time scales. This paper introduces the principle of transient absorption, typical dynamic processes and the application of femtosecond transient absorption spectroscopy in photocatalysis, and summarizes the bottlenecks faced by ultrafast spectroscopy in photocatalytic applications, as well as future research directions and solutions. This will provide inspiration for understanding the charge transfer mechanism of photocatalytic processes.

2.
DNA Cell Biol ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39235407

ABSTRACT

Radiation-induced intestinal injury is one of the most common intestinal complications caused by pelvic and abdominal tumor radiotherapy, severely impacting patients' quality of life. Ionizing radiation, while killing tumor cells, inevitably damages healthy tissue. Radiation-induced enteropathy results from radiation therapy-induced intestinal tissue damage and inflammatory responses. This damage involves various complex molecular mechanisms, including cell apoptosis, oxidative stress, release of inflammatory mediators, disruption of immune responses, and imbalance of intestinal microbiota. A thorough understanding of these molecular mechanisms is crucial for developing effective prevention and treatment strategies.

3.
Dalton Trans ; 53(33): 14018-14027, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39105523

ABSTRACT

Metal halide perovskites with suitable energy band structures and excellent visible-light responses have emerged as promising photocatalysts for CO2 reduction to valuable chemicals and fuels. However, the efficiency of CO2 photocatalytic reduction often suffers from inefficient separation and sluggish transfer. Herein, a step-scheme (S-scheme) CsPbBr3/BiOBr photocatalyst with oxygen vacancies possessing intimate interfacial contact was fabricated by anchoring CsPbBr3 QDs on BiOBr-Ov nanosheets using a mild anti-precipitation method. The results showed that CsPbBr3/BiOBr-Ov-2 with an internal electric field (IEF) heterojunction exhibited a boosted evolution rate of 27.4 µmol g-1 h-1 (CO: 23.8 µmol g-1 h-1 and CH4: 3.6 µmol g-1 h-1) with an electron consumption rate (Relectron) of 76.4 µmol g-1 h-1, which was 5.9 and 3.2 times that of single CsPbBr3 and BiOBr-Ov, respectively. Density functional theory (DFT) calculations revealed that BiOBr with oxygen vacancies can effectively enhance the adsorption and activation of CO2 molecules. More importantly, in situ infrared Fourier transform spectroscopy (DRIFTS) spectra show the transformation process of the surface species, while the femtosecond transient absorption spectrum (fs-TA) reveals the charge transfer kinetics of the CsPbBr3/BiOBr-Ov. Overall, this work provides some guidance for the rational design of S-scheme heterojunctions and vacancy-engineered photocatalysts, which are expected to have potential applications in the fields of photocatalysis and solar energy conversion.

4.
BMC Cancer ; 24(1): 582, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38741069

ABSTRACT

BACKGROUND: Local recurrence after surgery and radiochemotherapy seriously affects the prognosis of locally advanced rectal cancer (LARC) patients. Studies on molecular markers related to the radiochemotherapy sensitivity of cancers have been widely carried out, which might provide valued information for clinicians to carry out individual treatment. AIM: To find potential biomarkers of tumors for predicting postoperative recurrence. METHODS: In this study, LARC patients undergoing surgery and concurrent radiochemotherapy were enrolled. We focused on clinicopathological factors and PTEN, SIRT1, p-4E-BP1, and pS6 protein expression assessed by immunohistochemistry in 73 rectal cancer patients with local recurrence and 76 patients without local recurrence. RESULTS: The expression of PTEN was higher, while the expression of p-4E-BP1 was lower in patients without local recurrence than in patients with local recurrence. Moreover, TNM stage, lymphatic vessel invasion (LVI), PTEN and p-4E-BP1 might be independent risk factors for local recurrence after LARC surgery combined with concurrent radiochemotherapy. CONCLUSIONS: This study suggests that PTEN and p-4E-BP1 might be potential biomarkers for prognostic prediction and therapeutic targets for LARC.


Subject(s)
Adaptor Proteins, Signal Transducing , Biomarkers, Tumor , Cell Cycle Proteins , Chemoradiotherapy , Neoplasm Recurrence, Local , PTEN Phosphohydrolase , Rectal Neoplasms , Humans , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/metabolism , PTEN Phosphohydrolase/metabolism , Male , Female , Middle Aged , Chemoradiotherapy/methods , Biomarkers, Tumor/metabolism , Aged , Prognosis , Adaptor Proteins, Signal Transducing/metabolism , Cell Cycle Proteins/metabolism , Phosphoproteins/metabolism , Adult , Neoplasm Staging
5.
RSC Adv ; 14(16): 11482-11512, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38595725

ABSTRACT

Over the past decade, transition metal (TM)-based electrodes have shown intriguing physicochemical properties and widespread applications, especially in the field of supercapacitor energy storage owing to their diverse configurations, composition, porosity, and redox reactions. As one of the most intriguing research interests, the design of porous architectures in TM-based electrode materials has been demonstrated to facilitate ion/electron transport, modulate their electronic structure, diminish strain relaxation, and realize synergistic effects of multi-metals. Herein, the recent advances in porous TM-based electrodes are summarized, focusing on their typical synthesis strategies, including template-mediated assembly, thermal decomposition strategy, chemical deposition strategy, and host-guest hybridization strategy. Simultaneously, the corresponding conversion mechanism of each synthesis strategy are reviewed, and the merits and demerits of each strategy in building porous architectures are also discussed. Subsequently, TM-based electrode materials are categorized into TM oxides, TM hydroxides, TM sulfides, TM phosphides, TM carbides, and other TM species with a detailed review of their crystalline phase, electronic structure, and microstructure evolution to tune their electrochemical energy storage capacity. Finally, the challenges and prospects of porous TM-based electrode materials are presented to guide the future development in this field.

6.
ChemSusChem ; 17(13): e202301952, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38380968

ABSTRACT

Engineering low-cost electrocatalysts with desired features is vital to decrease the energy consumption but challenging for superior water splitting. Herein, we development a facile strategy by the addition of multivalence ruthenium (Ru) into the CoWO4/CC system. During the synthesis process, the most of Ru3+ ions were insinuated into the lattice of CoWO4, while the residual Ru3+ ions were reduced to metallic Ru and further attached to the interface between carbon cloth and CoWO4 sheets. The optimal Ru2(M)-CoWO4/CC exhibited superior performance for the HER with an overpotential of 85 mV@10 mA cm-2, which was much better than most of reported electrocatalysts, regarding OER, a low overpotential of 240 mV@10 mA cm-2 was sufficient. In comparison to Ru2(0)-CoWO4/CC with the same Ru mass loading, multivalence Ru2(M)-CoWO4/CC required a lower overpotential for OER and HER, respectively. The Ru2(M)-CoWO4/CC couple showed excellent overall water splitting performance at a cell voltage of 1.48 V@10 mA cm-2 for used as both anodic and cathodic electrocatalysts. Results of the study showed that the electrocatalytic activity of Ru2(M)-CoWO4/CC was attributed to the in-situ transformation of Ru/Co sites, the multivalent Ru ions and the synergistic effect of different metal species stimulated the intrinsic activity of CoWO4/CC.

7.
J Colloid Interface Sci ; 643: 480-488, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37088051

ABSTRACT

Ru-melem and Ru-C3N4 were synthesized by a simple and facile strategy to construct a novel covalently anchoring by introducing easily synthesized amide bond as a bridge connecting the Ru-terpy and melem or g-C3N4, respectively. The covalent anchoring of Ru complex on melem or C3N4 not only makes these materials exhibit water oxidation activity under CeIV-driven (CeIV = Ce(NH4)2(NO3)6) reaction condition, but also makes the obtained heterogeneous catalysts show higher catalytic activity than the corresponding homogeneous catalysts, which reveals that the covalent anchoring strategy of Ru complex is beneficial to improve the catalytic activity of homogeneous Ru catalysts. The synthetic method of hybrid catalysts offers an insightful strategy for enhancing water oxidation activity of molecular catalysts.

8.
Dose Response ; 20(3): 15593258221113791, 2022.
Article in English | MEDLINE | ID: mdl-35859853

ABSTRACT

Radiation-induced intestinal injury (RIII) restricts the therapeutic efficacy of radiotherapy in abdominal or pelvic malignancies. Also, intestinal injury is a major cause of death following exposure to high doses of radiation in nuclear accidents. No safe and effective prophylactics or therapeutics for RIII are currently available. Here, we reported that the apigenin, a natural dietary flavone, prolonged the survival in c57 mice after lethal irradiation. Apigenin pretreatment brought about accelerated restoration of crypt-villus structure, including enhanced regenerated crypts, more differentiated epithelium cells, and increased villus length. In addition, intestinal crypt cells in the apigenin-treated group exhibited more proliferation and less apoptosis. Furthermore, apigenin increased the expression of Nrf2 and its downstream target gene HO-1, and decreased oxidative stress after irradiation. In conclusion, our findings demonstrate the radioprotective efficacy of apigenin. Apigenin has the potential to be used as a radioprotectant in cancer therapy and nuclear accidents.

9.
Anal Methods ; 14(19): 1922-1927, 2022 05 19.
Article in English | MEDLINE | ID: mdl-35527509

ABSTRACT

A flap endonuclease 1 (FEN 1)-assisted swing arm DNA walker was constructed to achieve the signal amplification detection of ctDNA. The MB-labeled hairpin DNA was designed as the track and a long swing-arm DNA strand as the capture probe. The introduction of ctDNA unlocked a helper hairpin DNA, which could be captured to form the DNA duplex walker with the capture probe, and also activated the catalyst hairpin assembly. The DNA duplex walker opened the hairpin track and formed a three-base overlapping DNA structure, which was recognized and cleaved by FEN 1. Driven by the FEN 1 and the high reaction temperature, the DNA walker was initiated to hybridize with the track DNA and release multiple MB-labeled flaps for signal amplification. Owing to the excellent amplification capacity of the target recycling-induced DNA walker and programmed catalysis hairpin assembly, the one-step biosensor showed a linear detection range from 1 fM to 100 pM with a detection limit of 0.33 fM. Moreover, the sensitive detection of ctDNA in serum samples was verified, suggesting its potential application in liquid biopsy for clinical diagnosis.


Subject(s)
Biosensing Techniques , Circulating Tumor DNA , DNA , Flap Endonucleases/genetics , Limit of Detection
10.
Front Oncol ; 12: 1100481, 2022.
Article in English | MEDLINE | ID: mdl-36741692

ABSTRACT

Background: Radiotherapy (RT) is one of the most important treatments for patients with colorectal cancer (CRC). Radioresistance is the crucial cause of poor therapeutic outcomes in colorectal cancer. However, the underlying mechanism of radioresistance in colorectal cancer is still poorly defined. Herein we established a radioresistant colorectal cancer cell line and performed transcriptomics analyses to search for the underlying genes that contribute to radioresistance and investigate its association with the prognosis of CRC patients. Methods: The radioresistant cell line was developed from the parental HCT116 cell by a stepwise increased dose of irradiation. Differential gene analysis was performed using cellular transcriptome data to identify genes associated with radioresistance, from which extracellular matrix (ECM) and cell adhesion-related genes were screened. Survival data from a CRC cohort in the TCGA database were used for further model gene screening and validation. The correlation between the risk score model and tumor microenvironment, clinical phenotype, drug treatment sensitivity, and tumor mutation status were also investigated. Results: A total of 493 different expression genes were identified from the radioresistant and wild-type cell line, of which 94 genes were associated with ECM and cell adhesion-related genes. The five model genes TNFRSF13C, CD36, ANGPTL4, LAMB3, and SERPINA1 were identified for CRC radioresistance via screening using the best model. A ROC curve indicated that the AUC of the resulting prognostic model (based on the 5-gene risk score and other clinical parameters, including age, sex, and tumor stages) was 0.79, 0.77, and 0.78 at 1, 2, and 3 years, respectively. The calibration curve showed high agreement between the risk score prediction and actual survival probability. The immune microenvironment, drug treatment sensitivity, and tumor mutation status significantly differed between the high- and low-risk groups. Conclusions: The risk score model built with five radioresistance genes in this study, including TNFRSF13C, CD36, ANGPTL4, LAMB3, and SERPINA1, showed favorable performance in prognosis prediction after radiotherapy for CRC.

11.
Front Oncol ; 11: 796839, 2021.
Article in English | MEDLINE | ID: mdl-34869045

ABSTRACT

The transcription suppressor factor FBI-1 (the factor that binds to inducer of short transcripts-1) is an important regulator of hepatocellular carcinoma (HCC). In this work, the results showed that FBI-1 promoted the Warburg effect and enhances the resistance of hepatocellular carcinoma cells to molecular targeted agents. Knockdown of FBI-1 via its small-interfering RNA (siRNA) inhibited the ATP level, lactate productions, glucose uptake or lactate dehydrogenase (LDH) activation of HCC cells. Transfection of siFBI-1 also decreased the expression of the Warburg-effect-related factors: hypoxia-inducible factor-1 alpha (HIF-1α), lactate dehydrogenase A (LDHA), or GLUT1, and the epithelial-mesenchymal transition-related factors, Vimentin or N-cadherin. The positive correlation between the expression of FBI-1 with HIF-1α, LDHA, or GLUT1 was confirmed in HCC tissues. Mechanistically, the miR-30c repressed the expression of HIF-1α by binding to the 3'-untranslated region (3'-UTR) of HIF-1α in a sequence-specific manner, and FBI-1 enhanced the expression of HIF-1α and HIF-1α pathway's activation by repressing the expression of miR. By modulating the miR-30c/HIF-1α, FBI-1 promoted the Warburg effect or the epithelial-mesenchymal transition of HCC cells and promoted the resistance of HCC cells to molecular targeted agents.

12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 975-982, 2021 Jun.
Article in Chinese | MEDLINE | ID: mdl-34105503

ABSTRACT

OBJECTIVE: To analyze and predict the effect of coronavirus infection on hematopoietic system and potential intervention drugs, and explore their significance for coronavirus disease 2019 (COVID-19). METHODS: The gene expression omnibus (GEO) database was used to screen the whole genome expression data related with coronavirus infection. The R language package was used for differential expression analysis and KEGG/GO enrichment analysis. The core genes were screened by PPI network analysis using STRING online analysis website. Then the self-developed apparent precision therapy prediction platform (EpiMed) was used to analyze diseases, drugs and related target genes. RESULTS: A database in accordance with the criteria was found, which was derived from SARS coronavirus. A total of 3606 differential genes were screened, including 2148 expression up-regulated genes and 1458 expression down-regulated genes. GO enrichment mainly related with viral infection, hematopoietic regulation, cell chemotaxis, platelet granule content secretion, immune activation, acute inflammation, etc. KEGG enrichment mainly related with hematopoietic function, coagulation cascade reaction, acute inflammation, immune reaction, etc. Ten core genes such as PTPRC, ICAM1, TIMP1, CXCR5, IL-1B, MYC, CR2, FSTL1, SOX1 and COL3A1 were screened by protein interaction network analysis. Ten drugs with potential intervention effects, including glucocorticoid, TNF-α inhibitor, salvia miltiorrhiza, sirolimus, licorice, red peony, famciclovir, cyclosporine A, houttuynia cordata, fluvastatin, etc. were screened by EpiMed plotform. CONCLUSION: SARS coronavirus infection can affect the hematopoietic system by changing the expression of a series of genes. The potential intervention drugs screened on these grounds are of useful reference significance for the basic and clinical research of COVID-19.


Subject(s)
COVID-19 , Follistatin-Related Proteins , Hematopoietic System , Pharmaceutical Preparations , Computational Biology , Humans , SARS-CoV-2
13.
Int J Biol Sci ; 16(11): 1989-2000, 2020.
Article in English | MEDLINE | ID: mdl-32398965

ABSTRACT

The epidermal growth factor receptor (EGFR) family members EGFR and HER2 play pivotal roles in oncogenesis and tumor progression. Anticancer drugs targeting EGFR and HER2 have been developed. Long noncoding RNAs (lncRNAs) have been reported to regulate cancer development and progression through signaling pathways. However, lncRNAs that regulate EGFR and HER2 expression remain unknown. Here, we show that lncRNA myosin light chain kinase-antisense RNA 1 (MYLK-AS1) promotes EGFR and HER2 expression and activates their downstream signaling pathway. MYLK-AS1 increases hepatocellular carcinoma (HCC) cell proliferation, migration, and invasion in vitro. Consistently, MYLK-AS1 knockdown hinders tumor growth in vivo. Mechanistically, MYLK-AS1 enhances HCC cell proliferation, migration, and invasion through stimulating the EGFR/HER2-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. In addition, MYLK-AS1 is overexpressed in HCC patients and negatively correlated with HCC prognosis. Thus, MYLK-AS1 is an upstream regulator of EGFR/HER2, and acts as an oncogene, suggesting an additional target for cancer therapeutics.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Liver Neoplasms/metabolism , RNA, Long Noncoding/metabolism , Receptor, ErbB-2/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , ErbB Receptors/genetics , ErbB Receptors/metabolism , Extracellular Signal-Regulated MAP Kinases/genetics , Gene Expression Regulation, Neoplastic , Humans , MAP Kinase Kinase 1/genetics , MAP Kinase Kinase 1/metabolism , MAP Kinase Kinase Kinase 2/genetics , MAP Kinase Kinase Kinase 2/metabolism , MAP Kinase Signaling System , RNA, Long Noncoding/genetics , Receptor, ErbB-2/genetics , raf Kinases/genetics , raf Kinases/metabolism , ras Proteins/genetics , ras Proteins/metabolism
14.
Stem Cells Dev ; 29(10): 648-654, 2020 05 15.
Article in English | MEDLINE | ID: mdl-32122266

ABSTRACT

To remedy the lack of human leukocyte antigen (HLA)-matched donors and address the problems bedeviling traditional allogeneic hematopoietic stem cell transplantation which induces the resultant graft-versus-host disease, we designed a scheme called HLA-mismatched hematopoietic stem cell microtransplantation (MST) for patients with acute myeloid leukemia (AML), where encouraging results were achieved. In providing answers to such questions as how to select the donors of MST and which factors were involved in the outcome of MST. One hundred thirty-one AML patients from four centers with lower or standard risk of prognosis after complete remission were given three courses of MST: high dose of cytarabine plus infusion of granulocyte colony-stimulating factor mobilized peripheral blood stem cells from HLA-mismatched donors. Leukemia-free survival (LFS) and overall survival were compared, with respect to gender difference, number of HLA-matched loci, killer cell immunoglobulin-like receptor (KIR), and ligand mismatch between donors and recipients. Median LFS of recipients with different KIR ligands from those of donors was found to be significantly higher than that of recipients having identical ligands with donors (P < 0.05). The mean LFS was statistically different between recipients whose donors had HLA-C1/C2 ligand and those whose donors had C1/C1 or C2/C2 ligand (P < 0.05). The following factors were found to promote long-term survival: female recipients of male donors' stem cell, and donors with different KIR ligands from recipients.


Subject(s)
Donor Selection , Hematopoietic Stem Cells/metabolism , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/therapy , Adolescent , Adult , Disease-Free Survival , Donor Selection/methods , Female , Graft vs Host Disease/etiology , Granulocyte Colony-Stimulating Factor/metabolism , Hematopoietic Stem Cells/immunology , Humans , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Remission Induction/methods , Young Adult
16.
Chem Commun (Camb) ; 55(17): 2529-2532, 2019 Feb 21.
Article in English | MEDLINE | ID: mdl-30742154

ABSTRACT

[Fe2(TPA)2(µ-O)Cl2]2+ (TPA = tris(2-pyridylmethyl)amine) was investigated as a pre-catalyst, and greatly enhanced the photocatalytic water oxidation activity of BiVO4. An extremely high oxygen yield of 99.1% and apparent quantum yield of 44.3% were obtained in the BiVO4-NaIO3 photocatalytic water oxidation system.

17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 34(6): 535-540, 2018 Jun.
Article in Chinese | MEDLINE | ID: mdl-30236207

ABSTRACT

Objective To purify recombinant protein of human von Hippel-Lindau (VHL) and identify its function. Methods VHL gene sequence was amplified from human mammary cDNA using PCR and inserted into the prokaryotic expression vector pGEX-KG. Glutathione S-transferase-VHL (GST-VHL) recombinant plasmid we obtained was converted into BL21(DE3) sensitive bacteria to induce a small amount of GST-VHL protein. The expressed product was detected by SDS-PAGE and Western blot analysis. The recombinant protein was purified by GST beads and its function was verified by GST pull-down assay. Results The obtained recombinant plasmid could be successfully digested by double enzymes. Gene sequencing showed that the VHL sequence was correct and there was no mutation. The recombinant protein with approximately relative molecular mass (Mr) 56 000 was purified by converting recombinant plasmid to BL21(DE3) sensitive bacteria and inducing it in small quantities. GST pull-down assay verified that GST-VHL recombinant protein had the function of binding hypoxia inducible factor-1 α (HIF-1 α) in vitro. Conclusion GST-VHL recombinant protein is purified and can combine with HIF-1α protein in vitro.


Subject(s)
Von Hippel-Lindau Tumor Suppressor Protein/metabolism , Cloning, Molecular , Humans , Protein Binding , Recombinant Proteins , Von Hippel-Lindau Tumor Suppressor Protein/genetics
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(2): 432-436, 2018 Apr.
Article in Chinese | MEDLINE | ID: mdl-29665911

ABSTRACT

OBJECTIVE: To investigate the efficacy and safety of high-dose methotrexate-based chemotherapy combined with granulocyte-colony stimulating factor (G-CSF)-mobilized family related haploidentical donor peripheral blood hematopoietic stem cell (G-PBHSC) infusion for the treatment of patients with refractory primary central nervouse system lymphoma (PCNSL). METHODS: Three patients with refractory PCNSL were treated in Department of Hematology of the General Hospital of the PLA's Rocket Force from March 2014 to September 2015. The sex ratio of male to female was 1:2 and the median age was 54(48-66)years old. All patients received programmed infusions of G-PBHSC after high-dose methotrexate-based chemotherapy without prophylaxis for graft-versus-host disease (GVHD). RESULTS: Three patients had received initial chemotherapy or radiotherapy after diagnosis, one patient achieved complete remission (CR) after 3 courses of treatment and remained in CR until the end of follow-up, 2 cases achieved partial remission (PR) and the progression-free survival (PFS) time was 10 and 7 months, respectively. The patients generally well-tolerated this therapy. The main adverse effects of patients were neutropenia, thrombocytopenia and infection related with chemotherapy after each course of treatment, the median recovery times of neutrophils and platelets were 11 and 12.5 days, respectively after of programmed infusions of G-PBHSC. No GVHD was observed in any of the patients during treatment. CONCLUSION: The combination of high-dose methotrexate-based chemotherapy with programmed haploidentical G-PBHSC infusion is a potential treatment alternative for refractory PCNSL patients.


Subject(s)
Lymphoma , Aged , Antineoplastic Combined Chemotherapy Protocols , Female , Granulocyte Colony-Stimulating Factor , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Humans , Male , Methotrexate , Middle Aged , Treatment Outcome
19.
JAMA Oncol ; 4(1): 54-62, 2018 Jan 01.
Article in English | MEDLINE | ID: mdl-28910431

ABSTRACT

IMPORTANCE: The outcome of older patients with acute myeloid leukemia (AML) remains unsatisfactory. Recent studies have shown that HLA-mismatched microtransplant could improve outcomes in such patients. OBJECTIVE: To evaluate outcomes in different age groups among older patients with newly diagnosed AML who receive HLA-mismatched microtransplant. DESIGN, SETTING, AND PARTICIPANTS: This multicenter clinical study included 185 patients with de novo AML at 12 centers in China, the United States, and Spain in the Microtransplantation Interest Group. Patients were divided into the following 4 age groups: 60 to 64 years, 65 to 69 years, 70 to 74 years, and 75 to 85 years. The study period was May 1, 2006, to July 31, 2015. EXPOSURES: Induction chemotherapy and postremission therapy with cytarabine hydrochloride with or without anthracycline, followed by highly HLA-mismatched related or fully mismatched unrelated donor cell infusion. No graft-vs-host disease prophylaxis was used. MAIN OUTCOMES AND MEASURES: The primary end point of the study was to evaluate the complete remission rates, leukemia-free survival, and overall survival in different age groups. Additional end points of the study included hematopoietic recovery, graft-vs-host disease, relapse rate, nonrelapse mortality, and other treatment-related toxicities. RESULTS: Among 185 patients, the median age was 67 years (range, 60-85 years), and 75 (40.5%) were female. The denominators in adjusted percentages in overall survival, leukemia-free survival, relapse, and nonrelapse mortality are not the sample proportions of observations. The overall complete remission rate was not significantly different among the 4 age groups (75.4% [52 of 69], 70.2% [33 of 47], 79.1% [34 of 43], and 73.1% [19 of 26). The 1-year overall survival rates were 87.7%, 85.8%, and 77.8% in the first 3 age groups, which were much higher than the rate in the fourth age group (51.7%) (P = .004, P = .008, and P = .04, respectively). The 2-year overall survival rates were 63.7% and 66.8% in the first 2 age groups, which were higher than the rates in the last 2 age groups (34.2% and 14.8%) (P = .02, P = .03, P < .001, and P < .001, respectively). The 1-year cumulative incidences of nonrelapse mortality were 10.2%, 0%, 3.4%, and 26.0% in the 4 age groups and 8.1% in all patients. The median times to neutrophil and platelet recovery were 12 days and 14 days after induction chemotherapy, respectively. Five patients had full or mixed donor engraftment, and 30.8% (8 of 26) of patients demonstrated donor microchimerism. Two patients (1.1%) developed severe acute graft-vs-host disease. CONCLUSIONS AND RELEVANCE: Microtransplant achieved a high complete remission rate in AML patients aged 60 to 85 years and higher 1-year overall survival in those aged 60 to 74 years.


Subject(s)
Aging , Allografts/physiology , Hematopoietic Stem Cell Transplantation/methods , Leukemia, Myeloid, Acute/epidemiology , Leukemia, Myeloid, Acute/therapy , Age of Onset , Aged , Aged, 80 and over , Aging/immunology , Allografts/immunology , China/epidemiology , Female , Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Histocompatibility Testing/adverse effects , Histocompatibility Testing/statistics & numerical data , Humans , Leukemia, Myeloid, Acute/diagnosis , Male , Middle Aged , Remission Induction , Spain/epidemiology , Survival Analysis , Treatment Outcome , United States/epidemiology , Unrelated Donors
20.
Acta Haematol ; 138(3): 168-174, 2017.
Article in English | MEDLINE | ID: mdl-29045939

ABSTRACT

Nowadays, the regular recommended dose of decitabine for the treatment of myelodysplastic syndrome (MDS) is 20 mg/m2/day for 5 consecutive days with a relatively high incidence of treatment-related morbidities and costs. In this study, a retrospective and multicenter analysis was performed to explore the very-low-dose decitabine schedule for the treatment of patients with IPSS intermediate- or high-risk MDS. A total of 31 newly diagnosed MDS cases from 14 hospitals in Beijing received decitabine monotherapy (decitabine 6 mg/m2/day intravenously for 7 consecutive days, repeated every 4 weeks). With a medium follow-up of 4 months, 10 patients achieved complete remission (32.3%), 8 (25.8%) partial remission, and 3 (9.7%) hematological improvement. The overall response rate (ORR) was 67.7%. Rates of 21.7% for severe infections and 11.6% for severe bleedings were observed among all courses. The median cost of each course was USD 5,300, 3,000, 2,900, and 2,000, respectively. Multivariate analysis identified bone marrow blast cells ≥10% and a Charlson comorbidity index ≥1 as 2 independent factors for efficacy. In conclusion, very-low-dose decitabine showed relatively good efficacy, good tolerance, and low medical cost in the treatment of intermediate- or high-risk MDS. Elderly patients with more than 1 complication or patients with a higher proportion of blast cells may be the most suitable candidates for this regimen.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Azacitidine/analogs & derivatives , Myelodysplastic Syndromes/drug therapy , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/adverse effects , Azacitidine/adverse effects , Azacitidine/therapeutic use , Costs and Cost Analysis , DNA-Binding Proteins/genetics , Decitabine , Dioxygenases , Female , Hemorrhage/etiology , Humans , Injections, Intravenous , Male , Middle Aged , Multivariate Analysis , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/economics , Polymorphism, Genetic , Proto-Oncogene Proteins/genetics , Retrospective Studies , Risk , Treatment Outcome
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