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1.
Cancer Med ; 12(24): 21725-21734, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37975251

RESUMO

BACKGROUND: Brentuximab vedotin (BV) was approved as a therapy for patients with CD30-positive lymphoma in China in 2020 based on the results of multiple clinical trails. Few Chinese real-world data of its use are yet available. Herein, we present the application situation of BV in patients with lymphoma among different hospitals in Henan province in China under real-world conditions. METHODS: This was a multicenter and retrospective study in 104 patients with lymphoma who received BV for the first time between August 2020 and September 2022 across eight centers in Henan province. Data on the clinical use, effectiveness and adverse events (AEs) of BV were extracted from patient medical records. Short-term effectiveness was assessed based on objective response rate (ORR), complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier method. Safety was also evaluated in our study. RESULTS: 104 lymphoma patients were enrolled in our study, who had completed a median of two cycles (range,1-8) of BV-based treatment. A total of 72.1% of patients were relapsed/refractory (R/R) lymphoma, and only 27.9% were previously untreated lymphoma who received BV in frontline treatment settings. Among them who received effectiveness evaluation, the ORR achieved 64.5% (CR 25.8%, PR 38.7%). After a median follow-up of 11 months, the 6-month PFS rate and OS rate achieved 77.2% and 90.1% respectively, and the 12-month PFS rate and OS rate achieved 77.2% and 79.9% respectively. In general, BV-based treatment was well-tolerated, with 38.5% incidence of grade ≥3 AEs. The most commonly reported AEs were hematologic disorders, especially neutropenia, with the incidence reaching 50.0%. CONCLUSIONS: BV-based regimens could be a promising therapeutic option with remarkable effectiveness and moderate toxicity in treating Chinese lymphoma patients with CD30 expression.


Assuntos
Doença de Hodgkin , Imunoconjugados , Linfoma , Humanos , Brentuximab Vedotin/uso terapêutico , Brentuximab Vedotin/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Imunoconjugados/efeitos adversos , Linfoma/tratamento farmacológico , Linfoma/induzido quimicamente
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(4): 1069-1076, 2023.
Artigo em Chinês | MEDLINE | ID: mdl-37551479

RESUMO

OBJECTIVE: To investigate the related factors of invasive transformation and prognosis for follicular lymphoma. METHODS: A total of 168 patients with follicular lymphoma at First Affiliated Hospital of Zhengzhou University from August 2015 to January 2021 were collected, and the significance of each index in histological transformation (HT) and prognosis were analyzed. RESULTS: Pathology grade3, Ki-67 index ≥40%, ß2MG>3 mg/L, LDH>245 U/L, POD24 and non-invasion of bone marrow were associated with HT. Univariate analysis showed that the high risk of FLIPI-2, pathological grade 3, Ki-67≥40%, anemia, ß2MG>3 mg/L, LDH>245 U/L and HT had significant adverse effects on PFS; ß2MG>3 mg/L, LDH>245 U/L, POD24 and HT had significant adverse effects on OS. Cox multivariate analysis showed that the ß2MG >3 mg/L and HT were independent risk factors of PFS, HT was independent risk factor of OS. CONCLUSION: The pathological grade, Ki-67, ß2MG, LDH, POD24 and bone marrow invasion of FL can predict the risk of HT. Meanwhile, ß2MG >3 mg/L and HT are significantly related to poor prognosis of FL.

3.
Langenbecks Arch Surg ; 407(4): 1647-1652, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35146548

RESUMO

PURPOSE: Extensive lymph node metastasis (ELM) can occur in some patients with T1 papillary thyroid cancer (PTC). However, the risk factors for ELM in patients with T1 PTC have not been fully explored. In this study, we aimed to examine the association between extranodal extension (ENE) and ELM in patients with T1 PTC. PATIENTS AND METHODS: We identified 645 consecutive patients who had T1 PTC initially resected at our centre. Clinical and pathological data were reviewed. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for ELM. RESULTS: ELM was identified in 3.9% of T1 PTC patients, and ENE was identified in 8.1% of patients. ENE was associated with male sex, large tumour size, more positive nodes, and comprehensive surgical treatment. In multivariate analysis, three variables were independently associated with ELM, including ENE (odds ratio [OR], 11.15; 95% confidence interval [CI], 4.54 to 27.30; P < 0.001), age (OR, 0.96; 95% CI, 0.93 to 0.99; P = 0.022), and tumour size (OR, 1.18; 95% CI, 1.06 to 1.31; P = 0.002). Bilateral multifocality and sex were not independently associated with ELM. CONCLUSION: ENE is a strong independent predictor of ELM in patients with T1 PTC. Patients with ENE-positive nodes might need extensive neck dissection.


Assuntos
Carcinoma Papilar , Carcinoma , Neoplasias da Glândula Tireoide , Carcinoma/cirurgia , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Extensão Extranodal , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Esvaziamento Cervical , Estudos Retrospectivos , Fatores de Risco , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia
4.
Risk Anal ; 42(12): 2823-2834, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35034366

RESUMO

For safety-critical systems such as aircrafts and submarines, mission abort is commonly deployed to enhance system survivability at the cost of reducing mission success probability. In addition to mission abort, protective device can also mitigate the failure risk of safety-critical systems by reducing the magnitude of external shocks. Considering the effect of protective device on system failure behavior, this article proposes a condition-based mission abort policy where a mission is terminated and rescue procedure starts immediately if the state of system is worse than a control limit. Based on the developed mission abort policy, mission reliability and system survivability are evaluated to analyze the risk of mission failure and system failure. The optimal mission abort threshold balancing the tradeoff between mission reliability and system survivability is investigated. Furthermore, the joint optimization of mission abort and protective device selection policies is explored by simultaneously optimizing the defensive factor and abort threshold. A numerical example on a hydraulic system is presented to illustrate the applicability of the proposed policies.

5.
Front Immunol ; 12: 772450, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34938292

RESUMO

Background: There is no standard neoadjuvant therapy for locally advanced esophageal cancer in China. The role of neoadjuvant chemotherapy plus immunotherapy for locally advanced esophageal cancer is still being explored. Methods: This open-label, randomized phase II study was conducted at a single center between July 2019 and September 2020; 30 patients with locally advanced esophageal squamous cell carcinoma (ESCC) (T3, T4, or lymph-node positive) were enrolled. Patients were randomized according to the enrollment order at a 1:1 ratio to receive chemotherapy on day 1 and toripalimab on day 3 (experimental group) or chemotherapy and toripalimab on day 1 (control group). The chemotherapeutic regimen was paclitaxel and cisplatin. Surgery was performed 4 to 6 weeks after the second cycle of chemoimmunotherapy. The primary endpoint was pathological complete response (pCR) rate, and the secondary endpoint was safety and disease-free survival. Results: Thirty patients completed at least one cycle of chemoimmunotherapy; 11 in the experimental group and 13 in the control group received surgery. R0 resection was performed in all these 24 patients. Four patients (36%) in the experimental group and one (7%) in the control group achieved pCR. The experimental group showed a statistically non-significant higher pCR rate (p = 0.079). PD-L1 combined positive score (CPS) examination was performed in 14 patients; one in the control group had a PD-L1 CPS of 10, and pCR was achieved; the remaining 13 all had ≤1, and 11 of the 13 patients received surgery in which two (in the experimental group) achieved pCR. Two patients endured ≥grade 3 adverse events, and one suffered from grade 3 immune-related enteritis after one cycle of chemoimmunotherapy and dropped off the study. Another patient died from severe pulmonary infection and troponin elevation after surgery. Conclusions: Although the primary endpoint was not met, the initial results of this study showed that delaying toripalimab to day 3 in chemoimmunotherapy might achieve a higher pCR rate than that on the same day, and further large-sample clinical trials are needed to verify this. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03985670.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Imunoterapia , Terapia Neoadjuvante , Paclitaxel/administração & dosagem , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Esquema de Medicação , Neoplasias Esofágicas/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Feminino , Humanos , Imunoterapia/efeitos adversos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Paclitaxel/efeitos adversos , Resultado do Tratamento
6.
Carcinogenesis ; 42(2): 263-271, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32860508

RESUMO

Long non-coding RNAs (lncRNAs) regulate a series of biological processes, and their anomalous expression exerts critical roles in progression of multiple malignancies, including colorectal cancer (CRC). The present study was designed to provide new ideas and perspectives for the role of lncRNA MCF2L-AS1 and disclose the underlying mechanism in CRC. Herein, we observed that MCF2L-AS1 expression was enriched in CRC tissues and cell lines. Additionally, silencing of MCF2L-AS1 dramatically impeded cell proliferation, invasion and migration capacities of CRC, and distinctly attenuated the expression of invasion associated targets MMP-2 and MMP-9. Moreover, depletion of MCF2L-AS1 apparently restricted the glucose consumption and lactate production, and downregulated GLUT1 and LDHA expression. More importantly, we predicted and verified that MCF2L-AS1 acted as a molecular sponge for miR-874-3p and inversely regulated miR-874-3p expression. Interesting, FOXM1 was identified as direct target of miR-874-3p, and positively modulated by MCF2L-AS1 through sponging miR-874-3p. Mechanistically, MCF2L-AS1 accelerated cell proliferation, invasion and glycolysis through competitively binding to miR-874-3p, leading to enhance FOXM1 expression. Collectively, these outcomes highlighted that MCF2L-AS1 acted as a motivator by modulating the miR-874-3p/FOXM1 axis, thereby aggravating tumorigenesis and glycolysis progress of CRC, disclosing that MCF2L-AS1 may serve as a valuable and promising therapeutic strategy for CRC.


Assuntos
Neoplasias Colorretais/genética , Proteína Forkhead Box M1/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Humanos , Invasividade Neoplásica/genética , Efeito Warburg em Oncologia
7.
Oncotarget ; 8(15): 25469-25481, 2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-28424416

RESUMO

BACKGROUND: The genetic regulation of apoptosis and cell proliferation plays a role in the growth of chronic lymphocytic leukemia (CLL), the most common form of leukemia in the Western hemisphere. Although thyroid hormone receptor interactors (TRIPs) are known to play roles in cell cycle, the potential involvement of the novel family member TRIP13 in CLL has not yet been investigated. METHODS: Quantitative PCR (qPCR) was used to detect expression of TRIP13 in 36 CLL patients and 33 healthy donors CD19+ B cells. Loss-of-function (siRNA) assays were used to alter TRIP13 expression levels. The effect of TRIP13 on cell proliferation and apoptosis was measured by MTT, Annexin V-based flow cytometry and Caspase 3/7 activity assay. Affymetrix GeneChip and Ingenuity Pathway Analysis (IPA) were used to describe an overview of TRIP13 potential biological function and downstream pathways. Dual-luciferase reporter assay was performed to assess the promoting effect of c-MYC on TRIP13 transcription. RESULTS: The qPCR data showed that TRIP13 is significantly over-expressed in CLL patients. Microarray analyses indicated that the biological function of TRIP13 in CLL is majorly cell apoptosis and cell proliferation associated. TRIP13 siRNA expressing cells exhibited a slower cell proliferation rate and underwent apoptosis compared with control cells. TRIP13 knockdown induced CLL cells apoptosis through PUMA independent of p53. TRIP13 up-regulation is induced by c-MYC dependent transcriptional activation. CONCLUSION: Overall, our data suggest the bio-function of TRIP13 in CLL cell for the first time, and that this gene might be a therapeutic target for CLL.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/deficiência , Proteínas de Ciclo Celular/deficiência , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/metabolismo , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/fisiologia , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Receptores dos Hormônios Tireóideos/metabolismo , Análise de Sobrevida , Transfecção , Regulação para Cima
8.
Clin Chim Acta ; 457: 106-11, 2016 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-27071701

RESUMO

BACKGROUND: Plasma based EGFR mutation analysis is emerging as a viable alternative to tumour tissue genotyping for patients with non-small cell lung carcinoma (NSCLC). The purpose of the study was to determine the degree of concordance between EGFR genotypes derived from matching tissue and blood samples. METHODS: EGFR activating mutations L858R, exon 19 deletions, G719A/C/S and L861Q as well as resistance mutations T790M and exon 20 insertions were co-analysed in 61 matching tissue and blood biopsies collected from NCSLC patients. Tissue and plasma genotyping was performed by amplification refractory mutation system PCR (ARMS-PCR) and circulating single molecule amplification and re-sequencing technology (cSMART), respectively. RESULTS: Of the 61 paired samples, 44 (72.1%) were fully concordant, 2 (3.3%) were partially concordant and 15 (24.6%) were discordant for EGFR genotypes. The discordance was bidirectional with tissue and plasma failing to reveal the equivalent mutation in eight and nine cases, respectively. Benchmarking against ARMS-PCR tissue biopsy results as the gold standard, the sensitivity and concordance rates for plasma mutation detection by cSMART assay were 72.7% and 90.2% (L858R), 72.7% and 86.9% (exon 19 deletions) and 100% and 98.4% (T790M). CONCLUSIONS: The cSMART assay was highly reliable and accurate for plasma EGFR genotyping. Based on discordance trends, tumour heterogeneity was suspected to be the major factor preventing a concordant diagnosis in matching samples.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação , Carcinoma Pulmonar de Células não Pequenas/sangue , Humanos , Neoplasias Pulmonares/sangue
9.
Tumour Biol ; 37(8): 10851-60, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26883250

RESUMO

In spite of the fact that the great progress has been made in the treatment of non-small cell lung cancer (NSCLC), the prognosis of NSCLC remains comparatively dismal. Therefore, it is of great value to identify novel effective diagnostic biomarkers and therapeutic targets of NSCLC. Emerging evidence has demonstrated the vital roles of long noncoding RNAs (lncRNAs) in cancer development. ENST00000434223 was recently identified as a lncRNA that is downregulated in early stage lung adenocarcinoma in a profiling study. However, little is known about its role in the development of NSCLC. In the present study, we found that ENST00000434223 was greatly downregulated in cancer tissues compared to adjacent normal tissues. ENST00000434223 overexpression suppressed the proliferation and migration in NSCLC cell lines in vitro. Moreover, ENST00000434223 overexpression reversed the epithelial-mesenchymal transition in NSCLC cell line. Our study suggests that ENST00000434223 may be a potential biomarker and a therapeutic target of NSCLC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Transição Epitelial-Mesenquimal/genética , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/genética , Adulto , Idoso , Animais , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/genética , Progressão da Doença , Feminino , Citometria de Fluxo , Xenoenxertos , Humanos , Neoplasias Pulmonares/genética , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia de Fluorescência , Pessoa de Meia-Idade , RNA Longo não Codificante/biossíntese , Reação em Cadeia da Polimerase em Tempo Real
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