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1.
Environ Res ; 243: 117816, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38056614

RESUMO

Efficacious phosphate removal is essential for mitigating eutrophication in aquatic ecosystems and complying with increasingly stringent phosphate emission regulations. Chemical adsorption, characterized by simplicity, prominent treatment efficiency, and convenient recovery, is extensively employed for profound phosphorus removal. Metal-organic frameworks (MOFs)-derived metal/carbon composites, surpassing the limitations of separate components, exhibit synergistic effects, rendering them tremendously promising for environmental remediation. This comprehensive review systematically summarizes MOFs-based materials' properties and their structure-property relationships tailored for phosphate adsorption, thereby enhancing specificity towards phosphate. Furthermore, it elucidates the primary mechanisms influencing phosphate adsorption by MOFs-based composites. Additionally, the review introduces strategies for designing and synthesizing efficacious phosphorus capture and regeneration materials. Lastly, it discusses and illuminates future research challenges and prospects in this field. This summary provides novel insights for future research on superlative MOFs-based adsorbents for phosphate removal.


Assuntos
Estruturas Metalorgânicas , Fósforo , Água , Ecossistema , Fosfatos , Adsorção
2.
Environ Res ; 229: 116003, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37127106

RESUMO

The complexity of the chemistry behind the hydrothermal conversion is enormous. Components interact with their own physical and chemical structure, making it harsh to understand the conversion as a whole. Herein, the six-water recirculation and loading nano SiO2 experiment in a one-pot hydrothermal carbonization procedure was designed to elucidate the mechanism of regulating the functional groups and microporous structure of the hydrochar surface. The hydrochar prepared by the second circulating liquid and loading nano-SiO2 (HBC-R2/Si) was equipped most enriched functional groups (carboxyl = 11.48 µmol/g, phenolic hydroxyl = 52.98 µmol/g, lactone groups = 46.52 µmol/g) and suitable pore size (1.90 nm-1.93 nm) as a sorbent riched in hemicellulose. The sorption kinetics (equilibrium reached ≈ 480 min) are approximately evenly fitted by the pseudo-second-order, Weber and Morris, and Elovich models, indicating that membranes and particles diffusion, pore diffusion, and surface sorption coexisted in the sorption of methylene blue (MB) on the hydrochar materials. Simultaneously, all hydrochar materials achieved over 25% MB removal within 90 min (liquid membrane diffusion) and over 40% for HBC-R2 and HBC-R2/Si, suggesting that liquid membrane diffusion is the predominant rate-limiting step. Pearson's correlation analysis and Mantel's analysis announced that the cation exchange capacity (CEC), pore size, and carboxyl groups on the hemicellulose affect the sorption capacity by limiting the pore diffusion procedure. However, the CEC and the phenolic hydroxyl groups on the cellulose and hemicellulose affect the sorption rate by limiting membrane diffusion. Three consecutive sorption/desorption cycles confirmed the high stability and reusability of HBC-R2/Si composites.


Assuntos
Carbono , Celulose , Carbono/química , Cinética , Azul de Metileno/análise , Propriedades de Superfície , Adsorção
3.
BMC Cancer ; 22(1): 45, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996395

RESUMO

BACKGROUND: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. METHODS: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan-Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm. RESULTS AND CONCLUSIONS: Univariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell's concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.


Assuntos
Biomarcadores Tumorais/sangue , Linfoma de Burkitt , Adulto , Idoso , Linfoma de Burkitt/sangue , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/epidemiologia , Linfoma de Burkitt/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
4.
Int J Colorectal Dis ; 37(1): 251-258, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34716473

RESUMO

BACKGROUND AND OBJECTIVE: Immune checkpoint inhibitor (ICI) therapies have shown promising prospects in colorectal cancer (CRC) immunotherapy; many clinical trials have been carried out. In this study, we sought to evaluate the efficacy and safety of ICI therapies in CRC by presenting a meta-analysis of relevant studies. METHODS: Databases including PubMed, Embase, Cochrane Library, and Web of Science were systematically searched for studies concerning the efficacy and safety of ICI in colorectal cancer. The reported odds ratio (OR) or weighted mean difference (WMD) with 95% confidence intervals (CIs) of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), treatment-related adverse events (TRAEs), and TRAEs ≥ 3 in the included studies were analyzed by fixed effects/random effects models. RESULTS: Three studies involving 667 patients with colorectal cancer were included in our meta-analysis. No significant difference between the immune checkpoint inhibitor therapies and conventional therapies in OS (WMD = 0.73, 95% CI - 3.09, 4.54; p = 0.71), in ORR (OR = 1.54, 95% CI 0.98, 2.40; p = 0.06), and in DCR (OR = 0.97, 95% CI 0.36, 2.61; p = 0.95). The median PFS of the ICI therapy group was shorter than that of the conventional therapy group (WMD = - 0.10, 95% CI - 0.18, - 0.02; p = 0.02). At the same time, we also could not find a significant difference between the immune checkpoint inhibitor therapies and conventional therapies in TRAEs (OR = 1.56, 95% CI 0.11, 22.09; p = 0.74) and in TRAEs ≥ 3 (OR = 0.94, 95% CI 0.16, 5.65; p = 0.95). CONCLUSION: Immune checkpoint inhibitor therapies could not improve all survival endpoints to advanced or metastatic colorectal cancer patients. Whether immune checkpoint inhibitors should be the first choice of therapies for colorectal cancer patients with undetermined microsatellite status or not able to determine microsatellite status needs more related studies to prove.


Assuntos
Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Neoplasias Colorretais/tratamento farmacológico , Humanos , Imunoterapia/efeitos adversos , Intervalo Livre de Progressão
5.
BMC Pulm Med ; 22(1): 360, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36138362

RESUMO

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) is a rare and unique subtype of cancer that histologically resembles undifferentiated nasopharyngeal carcinoma (NPC). The population-based analysis of LELC and the optimal treatment remains unclear. MATERIALS AND METHODS: This real-world, retrospective study investigated 770 patients with LELC for primary site, treatment, and survival outcomes from 2005 to 2019 from five cancer centres in China. The overall survival (OS) of different subgroups was appraised by log-rank tests and Kaplan-Meier analysis. RESULTS: Primary sites LELC included the lung (597 cases, 77.5%), salivary gland (115 cases, 14.9%), and others. The median progression-free survival (PFS) of LELC patients was 47.4 months. The median overall survival (OS) was not reached. The 5-year survival rate for LELC patients was 77.8%. Most patients in stages I and II received surgery. The majority of patients in stage III received surgery and radiotherapy. More than half of the patients in stage IV received chemotherapy. Among relapsed or metastatic cases receiving chemotherapy, patients who received immunotherapy at any time presented with a superior OS than those without immunotherapy (P < 0.0001, HR = 0.39, 95% CI 0.25-0.63). Compared with the SEER database, patients with LELC had a better prognosis than NPC, with a 5-year overall survival of 77.3% vs. 56.8% (P < 0.001). CONCLUSION: Our data provide treatment patterns and outcomes for LELC from various primary sites. Randomized controlled studies are necessary to further define the standard of care for patients with LELC. Trial registration This clinical trial was registered at ClinicalTrials.gov (No. NCT04614818).


Assuntos
Carcinoma de Células Escamosas , Neoplasias Primárias Múltiplas , Carcinoma de Células Escamosas/patologia , Humanos , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
6.
J Clin Lab Anal ; 36(4): e24303, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35212022

RESUMO

BACKGROUND: RNA modification has become one of the hot topics of research as it can be used for tumor prognosis. However, its role in various biological processes is still poorly understood. The aim of this study was to investigate the role of m5 C and m1 A regulators on colorectal cancer prognosis using bioinformatics tools. The association between these regulators and differences in patient survival as well as the clinicopathological characteristics and tumor immune microenvironment in colorectal cancer tissues were assessed. METHODS: We selected publicly available colorectal cancer data sets from The Cancer Genome Atlas and used the "limma" package in R to identify differentially expressed genes. The least absolute shrinkage and selection operator regression model was used to calculate the prognostic risk, and a risk prediction model was constructed, to help assess the prognostic values of the differentially expressed genes. Finally, using TISCH and TIMER, we assessed the extent of cellular infiltration in colorectal cancer. RESULTS: We explored NSUN6 and DNMT3A expression using UALCAN and HPA and found that their expression is significantly increased in colorectal cancer tissues and correlated with sex and TP53 mutation status. Moreover, we found NSUN6 and DNMT3A were related to the infiltration of six major immune cells, with DNMT3A being closely related to dendritic cells, CD4+ T cells, and B cells, whereas NSUN6 to B cells and CD8+ T cells. CONCLUSION: Our findings suggest that m5 C regulators can predict the clinical prognostic risk and regulate the tumor immune microenvironment in colorectal cancer.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias Colorretais , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Humanos , Metilação , Prognóstico , RNA , Microambiente Tumoral/genética , tRNA Metiltransferases
7.
Cancer Cell Int ; 21(1): 261, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33985517

RESUMO

BACKGROUND: Burkitt lymphoma (BL) is a highly aggressive, fast-growing B-cell non-Hodgkin's lymphoma, manifested in several subtypes, including sporadic, endemic, and immunodeficiency-related forms, the mechanism of which is still not clear. Abundant evidence reported that KIF15 was involved in the progression of human cancer. The emphasis of this study is to explore the functions of KIF15 in the development of BL. METHODS: Firstly, tumor and normal tissues were collected for detecting expression of KIF15 in BL. Lentivirus-mediated shRNA knockdown of KIF15 was used to construct BL cell model, which was verified by qRT-PCR and Western Blot. The cell proliferation was detected by CCK8 assay, cell apoptosis and cell cycle were measured through flow cytometry. Transwell assay was conducted to detect the migration. RESULTS: We first found that KIF15 is highly expressed in BL. Knockdown of KIF15 can inhibit proliferation and migration, promote apoptosis and arrest the cell cycle. Moreover, KIF15 is involved in BL cell activity through regulating expression of apoptosis-related proteins (Caspase3, Caspase8, HTRA, IGFBP-6, p53, SMAC, sTNF-R1, TNF-ß and Bcl-2) and downstream pathways, such as p-Akt, CCND1, CDK6 and PIK3CA. CONCLUSIONS: These findings justify the search for small molecule inhibitors targeting KIF15 as a novel therapeutic strategy in BL.

8.
J Org Chem ; 86(3): 2810-2819, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33423498

RESUMO

A general and practical method for the synthesis of 5-trifluoromethylpyrazoles is reported that occurs by the coupling of hydrazonyl chlorides with environmentally friendly and large-tonnage industrial feedstock 2-bromo-3,3,3-trifluoropropene (BTP). This exclusively regioselective [3 + 2] cycloaddition of nitrile imines and with BTP is catalyst-free and operationally simple and features mild conditions, high yields, gram-scalable, a broad substrate scope, and valuable functional group tolerance. Significantly, our method has been applied for the synthesis of the key intermediate of an active agonist of sphingosine 1-phosphate receptor.


Assuntos
Iminas , Nitrilas , Catálise , Reação de Cicloadição
9.
Acta Pharmacol Sin ; 42(4): 641-647, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32737470

RESUMO

For follicular lymphoma (FL) with grade 1/2, the complete response (CR) rate of the first-line R-CHOP treatment was significantly low. In this study, we assessed the rationality of the administration of rituximab for FL patients with grade 1/2 based on concentration-response relationship analyses. Thus, we conducted a prospective pharmacokinetic (PK) study in 68 FL patients with grades 1-3 treated with R-CHOP at 21-day intervals. Plasma rituximab concentrations were quantified using ELISA and the population PK modeling was established with Phoenix® NLMETM. The first cycle trough concentration (C1-trough) of rituximab was a significant independent risk factor for achieving CR in matched-pair logistic regression analysis, rather than the concentrations in later cycles; the recommendatory minimum optimal C1-trough was 13.60 µg/mL. Patients with grade 1/2 had significantly lower C1-trough compared with grade 3 (12.21 µg/mL vs. 23.45 µg/mL, P < 0.001), only 30% patients with grade 1/2 could reach 13.60 µg/mL, compared with 91.67% in patients with grade 3, which was in accord with its unsatisfactory CR rates (43.33% vs. 76.32%). The stage indicating the tumor burden (the target) was a crucial influence factor for C1-trough, accounting for 40.70% of its variability, 70% patients with grade 1/2 were stage IV in this study, since the systemic therapy only started at the disseminated disease stage. The initial dose of 1800 mg was recommended by Monte Carlo simulation for patients with grade 1/2. In summary, low C1-trough accounted for low-grade FL's unsatisfactory CR rate, designing the first dosage of rituximab should be a very important component of individualized therapy for FL.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Rituximab/uso terapêutico , Adulto , Idoso , Antineoplásicos/farmacocinética , Ciclofosfamida/uso terapêutico , Relação Dose-Resposta a Droga , Doxorrubicina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método de Monte Carlo , Prednisona/uso terapêutico , Estudos Prospectivos , Rituximab/farmacocinética , Vincristina/uso terapêutico , Adulto Jovem
10.
Br J Haematol ; 189(5): 908-912, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32103494

RESUMO

To determine whether inflammatory markers, derived neutrophil-to-lymphocyte ratio (dNLR), haemoglobin/platelet ratio (HPR) or platelet/lymphocyte ratio (PLR) are predictive for prognosis in angioimmunoblastic T-cell lymphoma (AITL), we derived dNLR, HPR and PLR values for 110 AITL patients and appropriate cut-off point values to define overall survival (OS) and progression-free survival (PFS). dNLR ≥ 2·2, HPR ≥ 0·4 or PLR < 100 were significant factors for shorter OS and PFS. On univariate analysis, these three parameters were significantly associated with worse OS and PFS. On multivariate analysis, only dNLR remained a significant, independent prognostic factor for both OS and PFS.


Assuntos
Linfadenopatia Imunoblástica/sangue , Contagem de Leucócitos , Linfoma de Células T Periférico/sangue , Neutrófilos , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Transplante de Células-Tronco Hematopoéticas , Hemoglobinas/análise , Humanos , Linfadenopatia Imunoblástica/tratamento farmacológico , Linfadenopatia Imunoblástica/mortalidade , Linfadenopatia Imunoblástica/terapia , Inflamação/sangue , Contagem de Linfócitos , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/terapia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prednisolona/administração & dosagem , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento , Vincristina/administração & dosagem
11.
Cytokine ; 126: 154878, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31739215

RESUMO

Due to the variable overlap of multiple symptoms, accurate early diagnosis of NK/T-cell lymphoma-associated hemophagocytic syndrome (NK/T-LAHS) is difficult, making the prognosis extremely poor. Hemophagocytic syndrome (HPS) is now diagnosed primarily based on the hemophagocytic lymphohistiocytosis (HLH)-2004 diagnostic criteria, and platelet count is one of the baseline evaluations. However, in our study, the data showed that decreased platelets were not only a clinical feature of HPS but also the key cells that regulate inflammation by releasing α-granules containing upregulated platelet factor 4 (PF4) and downregulated platelet-derived growth factors (PDGFs). Furthermore, we found that angiopoietin-4 (ANG-4), which has significant differential expression, has been less reported, that may affect hematopoiesis and proinflammatory responses and can be used as diagnostic biomarkers together with PF4 and PDGFs.


Assuntos
Biomarcadores/sangue , Plaquetas/metabolismo , Citocinas/metabolismo , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfoma de Células T/complicações , Angiopoietinas/sangue , Angiopoietinas/genética , Estudos de Coortes , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Inflamação/sangue , Inflamação/complicações , Inflamação/genética , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/genética , Linfoma de Células T/diagnóstico , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Família Multigênica , Fator Plaquetário 4/sangue , Fator Plaquetário 4/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , Análise de Componente Principal , Estudos Retrospectivos , Células Th1/metabolismo , Regulação para Cima
12.
Ann Hematol ; 99(12): 2811-2819, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32975588

RESUMO

In the era of asparaginase-based therapy for extranodal natural killer/T cell lymphoma (ENKTL), the clinical outcomes of ENKTL have notably improved. However, as a rare subtype of ENKTL, the therapeutic effect and prognostic factors of non-nasal type ENKTL remain unclear. Thus, we performed this study to analyze the clinical characteristics and to establish a prognostic model specifically for the non-nasal disease. We performed a retrospective study of consecutive patients newly diagnosed with non-nasal type ENKTL and mainly received asparaginase-based therapy at Sun Yat-sen University Cancer Center (SYSUCC) between January 2011 and December 2019, to analyze the prognostic factors and to propose a prognostic model. We validated the prognostic model in an independent cohort. In total, 98 non-nasal type ENKTL patients were included in the training cohort. Multivariate analyses showed that prognostic factors for OS were elevated LDH levels, involvement of bone marrow and serum total protein (TP) < 60 g/L. We developed a new prognostic model named the non-nasal type ENKTL prognostic index (NPI) by grouping the prognostic factors: group 1, no risk factors; group 2, one risk factor; and group 3, two or three risk factors, which were associated with 3-year OS rates of 84.1% (95% CI, 70.9-97.2), 46.8% (27.7-65.8), and 14.9% (0-32.9), respectively (P < 0.001). These results were validated and confirmed in an independent cohort. The new model is efficient in distinguishing non-nasal-type ENKTL patients with various outcomes in the contemporary era of asparaginase-based therapy.


Assuntos
Antineoplásicos/uso terapêutico , Asparaginase/uso terapêutico , Linfoma Extranodal de Células T-NK/diagnóstico por imagem , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
13.
Cell Physiol Biochem ; 43(6): 2505-2515, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29131028

RESUMO

BACKGROUND/AIMS: Numerous studies have demonstrated that aberrant microRNA (miRNA) expression is involved in human disease including cancer. To date, the potential miRNAs regulating lung cancer growth and progression are not fully identified yet. METHODS: In this study, the expression of miR-142-5p was measured in non-small cell lung cancer tissue and cell lines by qRT-PCR. The functional assays including the cell viability, colony formation, cell migration and invasion were performed in miR-142-5p mimic or inhibitor transfected cell lines (in vitro) and the cell tumorigenesis in nude mice (in vivo). The fluorescence ratios of cell viability were recorded using a multi-plate reader (Synergy 2, BioTek, Winooski, VT, USA) and the colonies were counted using an ELIspot Bioreader 5000 (BIO-SYS, Karben, GE). RESULTS: MiR-142-5p was significantly downregulated in non-small cell lung cancer tissue and cell lines compared to normal human lung tissues. Overexpression of miR-142-5p resulted in decreased expression of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) at both mRNA and protein levels. We found that miR-142-5p overexpression markedly suppressed cell proliferation in vitro and in vivo. Conversely, inhibition of miR-142-5p promoted lung cancer growth. Mechanistic studies showed that PIK3CA was a potential target of miR-142-5p and it mediated reduction of PIK3CA resulting in suppression of PI3K/Akt pathway. CONCLUSIONS: Our results demonstrate that miR-142-5p functions as a growth suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA in non-small cell lung cancer.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/metabolismo , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Células A549 , Animais , Antagomirs/metabolismo , Sequência de Bases , Carcinogênese , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Classe I de Fosfatidilinositol 3-Quinases/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Mutagênese , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência , Transplante Heterólogo
15.
Genome Med ; 16(1): 48, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566223

RESUMO

BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is a clinically and genetically heterogeneous disease with poor prognosis. Genome sequencing and mutation characterization provides a powerful approach for patient stratification, treatment target discovery, and etiology identification. However, previous studies mostly concentrated on base-level mutations in primary NKTCL, whereas the large-scale genomic alterations in NKTCL and the mutational landscapes in relapsed/refractory NKTCL remain largely unexplored. METHODS: Here, we assembled whole-genome sequencing and whole-exome sequencing data from 163 patients with primary or relapsed/refractory NKTCL and compared their somatic mutational landscapes at both nucleotide and structure levels. RESULTS: Our study not only confirmed previously reported common NKTCL mutational targets like STAT3, TP53, and DDX3X but also unveiled several novel high-frequency mutational targets such as PRDM9, DST, and RBMX. In terms of the overall mutational landscape, we observed striking differences between primary and relapsed/refractory NKTCL patient groups, with the latter exhibits higher levels of tumor mutation burden, copy number variants (CNVs), and structural variants (SVs), indicating a strong signal of genomic instability. Complex structural rearrangements such as chromothripsis and focal amplification are also significantly enriched in relapsed/refractory NKTCL patients, exerting a substantial impact on prognosis. Accordingly, we devised a novel molecular subtyping system (i.e., C0-C4) with distinct prognosis by integrating potential driver mutations at both nucleotide and structural levels, which further provides an informative guidance for novel treatments that target these specific driver mutations and genome instability as a whole. CONCLUSIONS: The striking differences underlying the mutational landscapes between the primary and relapsed/refractory NKTCL patients highlight the importance of genomic instability in driving the progression of NKTCL. Our newly proposed molecular subtyping system is valuable in assisting patient stratification and novel treatment design towards a better prognosis in the age of precision medicine.


Assuntos
Linfoma Extranodal de Células T-NK , Humanos , Linfoma Extranodal de Células T-NK/genética , Linfoma Extranodal de Células T-NK/patologia , Mutação , Instabilidade Genômica , Nucleotídeos , Células Matadoras Naturais , Histona-Lisina N-Metiltransferase/genética
16.
Oral Oncol ; 148: 106656, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38065019

RESUMO

OBJECTIVES: To determine the extent of research waste in the field of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: In this cross-sectional study, we explored the rates, causes and predictors of discontinuation and nonpublication of NPC clinical trials. The sample was derived using the ClinicalTrials.gov advanced search function. Adjusted logistic regression was used to ascertain the effect of trial characteristics on completion and publication status. If a trial discontinuation explanation or publication status could not be determined through the systematic search, the corresponding author was emailed. RESULTS: Ultimately, 311 NPC clinical trials were included (255 [82.0 %] completed and 56 [18.0 %] discontinued trials). The most common reason for trial discontinuation was poor accrual (50 %, 23/46). Industry funding (adjusted OR, 3.12; P = 0.003) and recurrent/metastatic setting (adjusted OR, 11.95; P = 0.003) were significantly associated with increased likelihood of trial discontinuation. Of the 207 completed trials included in the publication query, 141 (68.1 %) were published in peer-reviewed journals, 10 (4.8 %) had results only available on ClinicalTrials.gov, and 56 (27.1 %) remained unpublished 3 or more years after trial completion. Radiation with or without pharmacologic interventions significantly increased the potential of publication (adjusted OR, 3.20; P = 0.048). Among published trials, the median time to publication was 28.47 months (interquartile range, 15.27-44.98 months). CONCLUSION: We identified the difficulties inherent in NPC clinical trials from completion to publication. This represents considerable research waste in NPC, thus raising ethical concerns about the concealment of clinical data and futile patient participation and attendant risks.


Assuntos
Neoplasias Nasofaríngeas , Humanos , Estudos Transversais , Carcinoma Nasofaríngeo , Modelos Logísticos , Neoplasias Nasofaríngeas/radioterapia
17.
Clin Exp Med ; 24(1): 64, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554186

RESUMO

Advanced diffuse large B cell lymphoma (DLBCL) is a common malignant tumor with aggressive clinical features and poor prognosis. At present, there is lack of effective prognostic tool for patients with advanced (stage III/IV) DLBCL. The aim of this study is to identify prognostic indicators that affect survival and response and establish the first survival prediction nomogram for advanced DLBCL. A total of 402 patients with advanced DLBCL were enrolled in this study. COX multivariate analysis was used to obtain independent prognostic factors. The independent prognostic factors were included in the nomogram, and the nomogram to predict the performance of the model was established by R rms package, C-index (consistency index), AUC curve and calibration curve. The training and validation cohorts included 281 and 121 patients. In the training cohort, multivariate analysis showed that Ki-67 (70% (high expression) vs ≤ 70% (low expression), p < 0.001), LDH (lactate dehydrogenase) (elevated vs normal, p = 0.05), FER (ferritin) (elevated vs normal, p < 0.001), and ß2-microglobulin (elevated vs normal, p < 0.001) were independent predictors and the nomogram was constructed. The nomogram showed that there was a significant difference in OS among the low-risk, intermediate-risk and high-risk groups, with 5-year survival rates of 81.6%, 44% and 6%, respectively. The C-index of the nomogram in the training group was 0.76. The internal validation of the training group showed good consistency. In the internal validation cohort of the training group, the AUC was 0.828, and similar results were obtained in the validation group, with a C-index of 0.74 and an AUC of 0.803. The proposed nomogram provided a valuable individualized risk assessment of OS in advanced DLBCL patients.


Assuntos
Linfoma Difuso de Grandes Células B , Nomogramas , Humanos , Prognóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Análise Multivariada
18.
Environ Sci Pollut Res Int ; 30(6): 15377-15391, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36169823

RESUMO

MnO2, as a representative manganese-based catalyst with many kinds of crystal forms, has been widely used to activate PMS. However, the role of morphological scale and crystal structures on the catalytic capability of MnO2 still lacks further study. In this study, four different crystal forms of MnO2 (α-MnO2, ß-MnO2, γ-MnO2, and δ-MnO2) are succeeded in being fabricated via hydrothermal processes and evaluated by activating PMS for the removal of Reactive Yellow X-RG, typical azo dye. Experiment results indicate that α-MnO2 with a one-dimensional structure exhibits the best catalytic performance among the four as-prepared MnO2, which can be attributed to its broadest crystal interplanar distance (0.692), the highest portion of Mn (III)/Mn (IV) (4.194), and lowest value of average oxidation state AOS (2.696). Correlation analysis confirms that interplanar distance is the most relative factor with the catalytic activity of MnO2 among the three studied factors (R2 = 0.99715). Meanwhile, the morphological scale structure of α-MnO2 can also account for its highest catalytic ability among the four as-prepared MnO2, including its large specific area and advantageous one-dimensional nanostructure. Furthermore, according to the response surface methodology, when the dosage of PMS is 2.369 g/L, the dosage of α-MnO2 is 0.991 g/L, and the initial dye concentration is 1025 mg/L, the maximum removal rate of Reactive Yellow X-RG is up to 97.38%.


Assuntos
Compostos de Manganês , Óxidos , Óxidos/química , Compostos de Manganês/química , Compostos Azo , Oxirredução , Manganês
19.
J Cancer Res Clin Oncol ; 149(11): 8863-8875, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37148293

RESUMO

PURPOSE: The objective of this research was to assess the utility of positron emission tomography combined with computed tomography (PET/CT) to detect bone marrow invasion (BMI) and the predictive value of PET/CT in extranodal natural killer/T-cell lymphoma (ENKTL) patients. PATIENTS AND METHODS: This multicentre study enrolled ENKTL patients who underwent pretherapy PET/CT and bone marrow biopsy (BMB). The specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV) of PET/CT and BMB for BMI were evaluated. Multivariate analysis was used to identify predictive parameters for constructing a nomogram. RESULTS: Seven hundred and forty-eight patients were identified from four hospitals, with eighty (10.7%) having focal skeletal lesions on PET/CT and fifty (6.7%) having positive BMB. When BMB is considered as the gold standard, the specificity, sensitivity, PPV, and NPV of PET/CT for diagnosing BMI were found to be 93.8%, 74.0%, 46.3%, and 98.1%, respectively. PET/CT-positive individuals showed significantly worse OS than PET/CT-negative patients in the subgroup of BMB-negative cases. The nomogram model created according to the significant risk factors from multivariate analysis performed well in predicting survival probability. CONCLUSION: PET/CT offers a superior degree of precision for determining BMI in ENKTL. A nomogram model including the parameters of PET/CT can predict survival probability and may help in applying appropriate personalized therapy.


Assuntos
Linfoma Extranodal de Células T-NK , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Linfoma Extranodal de Células T-NK/diagnóstico por imagem , Fluordesoxiglucose F18 , Estudos Retrospectivos , Biópsia , Células Matadoras Naturais , Tomografia por Emissão de Pósitrons/métodos
20.
Front Immunol ; 14: 1195659, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37622113

RESUMO

Background: Immunotherapy has been a hotspot in nasopharyngeal carcinoma (NPC) in recent years. This study aimed to provide a comprehensive landscape of the characteristics of immunotherapy clinical trials in NPC and to determine whether contemporary studies are of sufficient quality to demonstrate therapeutic value. Methods: This is a cross-sectional analysis of NPC trials registered on ClinicalTrials.gov in the last 15 years (Jan 1, 2008-Nov 20, 2022). Only interventional trials with a primary purpose of treatment were included in the final analysis. Characteristics of immunotherapy trials were compared with those of other NPC trials. Chronological shifts in NPC immunotherapy trials were also analyzed. Results: Of the 440 NPC studies selected, 161 (36.6%) were immunotherapy trials and 279 (63.4%) were other NPC trials. NPC immunotherapy trials were more likely than other NPC trials to be phase 1-2 (82.6% vs. 66.7%, P < 0.001), single-arm (51.3% vs. 39.6%, P = 0.020), non-randomized (64.8% vs. 44.4%, P < 0.001), and enroll fewer than 50 participants (46.3% vs. 34.4%, P = 0.015). Blinding was used in 8.8% of NPC immunotherapy trials. Also, 90.7% of NPC immunotherapy trials were recruited nationally and 82.6% were Asia-centric. Although academic institutions and governments (72.7%) were the major sponsors of NPC trials, immunotherapy trials were more likely to be industry-funded than other NPC trials (34.2% vs. 11.5%, P < 0.001). The number of NPC immunotherapy trials increased exponentially after 2017, attributed to the exploration of immune checkpoint inhibitors. Immunotherapy combined with chemotherapy was the most commonly investigated regimen. Conclusion: NPC immunotherapy trials over a 15-year period were predominantly exploratory. To generate high-quality evidence and advance the clinical application of immunotherapy in NPC, more attention and concerted efforts are needed.


Assuntos
Imunoterapia , Neoplasias Nasofaríngeas , Humanos , Estudos Transversais , Carcinoma Nasofaríngeo/terapia , Ásia , Neoplasias Nasofaríngeas/terapia
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