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1.
JHEP Rep ; 6(6): 101063, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38737600

RESUMO

Background & Aims: Inoperable hepatocellular carcinoma (HCC) can be treated by stereotactic body radiotherapy. However, carbon ion radiotherapy (CIRT) is more effective for sparing non-tumorous liver. High linear energy transfer could promote therapy efficacy. Japanese and Chinese studies on hypofractionated CIRT have yielded excellent results. Because of different radiobiological models and the different etiological spectrum of HCC, applicability of these results to European cohorts and centers remains questionable. The aim of this prospective study was to assess safety and efficacy and to determine the optimal dose of CIRT with active raster scanning based on the local effect model (LEM) I. Methods: CIRT was performed every other day in four fractions with relative biological effectiveness (RBE)-weighted fraction doses of 8.1-10.5 Gy (total doses 32.4-42.0 Gy [RBE]). Dose escalation was performed in five dose levels with at least three patients each. The primary endpoint was acute toxicity after 4 weeks. Results: Twenty patients received CIRT (median age 74.7 years, n = 16 with liver cirrhosis, Child-Pugh scores [CP] A5 [n = 10], A6 [n = 4], B8 [n = 1], and B9 [n = 1]). Median follow up was 23 months. No dose-limiting toxicities and no toxicities exceeding grade II occurred, except one grade III gamma-glutamyltransferase elevation 12 months after CIRT, synchronous to out-of-field hepatic progression. During 12 months after CIRT, no CP elevation occurred. The highest dose level could be applied safely. No local recurrence developed during follow up. The objective response rate was 80%. Median overall survival was 30.8 months (1/2/3 years: 75%/64%/22%). Median progression-free survival was 20.9 months (1/2/3 years: 59%/43%/43%). Intrahepatic progression outside of the CIRT target volume was the most frequent pattern of progression. Conclusions: CIRT of HCC yields excellent local control without dose-limiting toxicity. Impact and implications: To date, safety and efficacy of carbon ion radiotherapy for hepatocellular carcinoma have only been evaluated prospectively in Japanese and Chinese studies. The optimal dose and fractionation when using the local effect model for radiotherapy planning are unknown. The results are of particular interest for European and American particle therapy centers, but also of relevance for all specialists involved in the treatment and care of patients with hepatocellular carcinoma, as we present the first prospective data on carbon ion radiotherapy in hepatocellular carcinoma outside of Asia. The excellent local control should encourage further use of carbon ion radiotherapy for hepatocellular carcinoma and design of randomized controlled trials. Clinical Trials Registration: The study is registered at ClinicalTrials.gov (NCT01167374).

2.
Cancers (Basel) ; 16(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38610957

RESUMO

PURPOSE: Evaluation of the influence of intrinsic and extrinsic conditions on ablation zone volumes (AZV) after microwave ablation (MWA). METHODS: Retrospective analysis of 38 MWAs of therapy-naïve liver tumours performed with the NeuWave PR probe. Ablations were performed either in the 'standard mode' (65 W, 10 min) or in the 'surgical mode' (95 W, 1 min, then 65 W, 10 min). AZV measurements were obtained from contrast-enhanced computed tomography immediately post-ablation. RESULTS: AZVs in the 'standard mode' were smaller than predicted by the manufacturer (length 3.6 ± 0.6 cm, 23% below 4.7 cm; width 2.7 ± 0.6, 23% below 3.5 cm). Ablation zone past the tip was limited to 6 mm in 28/32 ablations. Differences in AZV between the 'surgical mode' and 'standard mode' were not significant (15.6 ± 7.8 mL vs. 13.9 ± 8.8 mL, p = 0.6). AZVs were significantly larger in case of hepatocellular carcinomas (HCCs) (n = 19) compared to metastasis (n = 19; 17.8 ± 9.9 mL vs. 10.1 ± 5.1 mL, p = 0.01) and in non-perivascular tumour location (n = 14) compared to perivascular location (n = 24, 18.7 ± 10.4 mL vs. 11.7 ± 6.1 mL, p = 0.012), with both factors remaining significant in two-way analysis of variance (HCC vs. metastasis: p = 0.02; perivascular vs. non-perivascular tumour location: p = 0.044). CONCLUSION: Larger AZVs can be expected in cases of HCCs compared with metastases and in non-perivascular locations. Using the 'surgical mode' does not increase AZV significantly.

3.
Front Oncol ; 14: 1287995, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549937

RESUMO

Purpose: Patients with advanced prostate cancer (PCa) often develop castration-resistant PCa (CRPC) with poor prognosis. Prognostic information obtained from multiparametric magnetic resonance imaging (mpMRI) and histopathology specimens can be effectively utilized through artificial intelligence (AI) techniques. The objective of this study is to construct an AI-based CRPC progress prediction model by integrating multimodal data. Methods and materials: Data from 399 patients diagnosed with PCa at three medical centers between January 2018 and January 2021 were collected retrospectively. We delineated regions of interest (ROIs) from 3 MRI sequences viz, T2WI, DWI, and ADC and utilized a cropping tool to extract the largest section of each ROI. We selected representative pathological hematoxylin and eosin (H&E) slides for deep-learning model training. A joint combined model nomogram was constructed. ROC curves and calibration curves were plotted to assess the predictive performance and goodness of fit of the model. We generated decision curve analysis (DCA) curves and Kaplan-Meier (KM) survival curves to evaluate the clinical net benefit of the model and its association with progression-free survival (PFS). Results: The AUC of the machine learning (ML) model was 0.755. The best deep learning (DL) model for radiomics and pathomics was the ResNet-50 model, with an AUC of 0.768 and 0.752, respectively. The nomogram graph showed that DL model contributed the most, and the AUC for the combined model was 0.86. The calibration curves and DCA indicate that the combined model had a good calibration ability and net clinical benefit. The KM curve indicated that the model integrating multimodal data can guide patient prognosis and management strategies. Conclusion: The integration of multimodal data effectively improves the prediction of risk for the progression of PCa to CRPC.

5.
Target Oncol ; 19(2): 213-221, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38416377

RESUMO

BACKGROUND: The combination of gemcitabine and cisplatin (gem/cis) with the anti-PD-L1-antibody durvalumab was recently approved as first line therapy for biliary tract cancer (BTC) based on the results of the TOPAZ-1 trial. OBJECTIVE: We aim to analyse the feasibility and efficacy of the triple combination therapy in patients with BTC in a real-world setting and in correspondence with the genetic alterations of the cancer. METHODS: In this single-centre retrospective analysis, all patients with BTC and treated with durvalumab plus gem/cis from April 2022 to September 2023 were included. Survival and treatment response were investigated, within the context of the inclusion and exclusion criteria of TOPAZ-1 and in correspondence with genetic alterations of the cancer. RESULTS: In total, 35 patients, of which 51% met the inclusion criteria of the TOPAZ-1 trial, were analysed. Patients treated within TOPAZ-1 criteria did not have a significantly different median overall survival and progression free survival than the rest of the patients (10.3 versus 9.7 months and 5.3 versus 5 months, respectively). The disease control rate of patients within the TOPAZ-1 criteria was 61.1%, in comparison to 58.8% in the rest of patients. A total of 51 grade 3 and 4 adverse events were observed without significant differences in the subgroups. No specific correlating patterns of genetic alterations with survival and response were observed. CONCLUSIONS: The treatment of advanced patients with BTC with durvalumab and gem/cis, even beyond the inclusion criteria of the TOPAZ-1 trial, shows promising safety.


Assuntos
Anticorpos Monoclonais , Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Humanos , Gencitabina , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/efeitos adversos , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/etiologia
6.
Cancers (Basel) ; 16(4)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38398162

RESUMO

BACKGROUND: ALPPS popularity is increasing among surgeons worldwide and its indications are expanding to cure patients with primarily unresectable liver tumors. Few reports recommended limitations or even contraindications of ALPPS in perihilar cholangiocarcinoma (phCC). Here, we discuss the results of ALPPS in patients with phCC in a systematic review as well as a pooled data analysis. METHODS: MEDLINE and Web of Science databases were systematically searched for relevant literature up to December 2023. All studies reporting ALPPS in the management of phCC were included. A single-arm meta-analysis of proportions was carried out to estimate the overall rate of outcomes. RESULTS: After obtaining 207 articles from the primary search, data of 18 studies containing 112 phCC patients were included in our systematic review. Rates of major morbidity and mortality were calculated to be 43% and 22%, respectively. The meta-analysis revealed a PHLF rate of 23%. One-year disease-free survival was 65% and one-year overall survival was 69%. CONCLUSIONS: ALPPS provides a good chance of cure for patients with phCC in comparison to alternative treatment options, but at the expense of debatable morbidity and mortality. With refinement of the surgical technique and better perioperative patient management, the results of ALPPS in patients with phCC were improved.

7.
Viruses ; 16(2)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38400083

RESUMO

Cytokines are signaling molecules that play a role in myriad processes, including those occurring during diseases and homeostasis. Their homeostatic function begins during embryogenesis and persists throughout life, including appropriate signaling for the cell and organism death. During viral infections, antiviral cytokines such as interferons and inflammatory cytokines are upregulated. Despite the well-known benefits of these cytokines, their levels often correlate with disease severity, linking them to unfavorable outcomes. In this review, we discuss both the beneficial and pathological functions of cytokines and the potential challenges in separating these two roles. Further, we discuss challenges in targeting these cytokines during disease and propose a new method for quantifying the cytokine effect to limit the pathological consequences while preserving their beneficial effects.


Assuntos
COVID-19 , Influenza Humana , Humanos , Citocinas , SARS-CoV-2 , Interferons
8.
PLoS Negl Trop Dis ; 17(10): e0011724, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37906617

RESUMO

BACKGROUND: Endocystectomy is a conservative surgical approach to managing cystic echinococcosis. Bile leakage is the main complication of this technique. The aim of this study was to evaluate the factors associated with bile leakage and to assess the outcomes and cost efficiency of strategies used to treat bile leakage. METHODOLOGY/PRINCIPAL FINDINGS: Patients who underwent endocystectomy between 2005 and 2020 were included. The preoperative characteristics, intra- and postoperative outcomes, hospital costs, and cost efficiency (the Diagnosis-Related Group reimbursement minus the overall cost) were evaluated prospectively. A total of eighty patients with 142 cysts were included. Postoperative complications occurred in 17 patients (21%), including 11 patients with bile leakage (type A: 1, type B: 6 and type C: 4 patients, total 13%). Bile leakage was more frequent in patients with preoperative MRI signs of cysto-biliary fistulas or intraoperative visible cysto-biliary fistulas (p = 0.03 and p = 0.04, respectively) and in patients with cysts larger than 8 cm (p = 0.03). Patients with bile leakage who underwent reoperation (type C) had significantly shorter hospital stays (9 vs. 16 days, p<0.01) and better cost efficiency than those who received radiologic or endocscopic interventions (€2,072 vs. -€2,097 p = 0.01). No mortality was observed, and recurrence was seen in two patients. CONCLUSIONS/SIGNIFICANCE: Endocystectomy is a safe and efficient technique. Preoperative and intraoperative cysto-biliary fistulas and a cyst diameter larger than 8 cm are correlated to postoperative bile leakage. Early operative management of bile leakage reduces hospital stay and improves cost efficiency compared with radiologic or endoscopic treatments.


Assuntos
Fístula Biliar , Cistos , Equinococose Hepática , Humanos , Fístula Biliar/etiologia , Fístula Biliar/cirurgia , Fístula Biliar/diagnóstico , Equinococose Hepática/cirurgia , Equinococose Hepática/diagnóstico , Fatores de Risco , Endoscopia , Estudos Retrospectivos
9.
Cancer Med ; 12(19): 19548-19559, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37737550

RESUMO

BACKGROUND: Statins, metformin, and aspirin have been reported to reduce the incidence of hepatocellular carcinoma (HCC). However, the effect of their perioperative use on survival outcomes of HCC patients following curative liver resection still remains unclear. METHOD: Three hundred and fifty three patients with a first diagnosis of HCC who underwent curative liver resection were included. Propensity score matching analysis with a users: nonusers ratio of 1:2 were performed for each of the medications (statins, metformin, and aspirin). Overall survival (OS) and recurrence-free survival (RFS) were evaluated and multivariable Cox proportional hazard analysis was performed. RESULTS: Sixty two patients received statins, 48 patients used metformin, and 53 patients received aspirin for ≥90 days before surgery. None of the medications improved OS. RFS of statin users was significantly longer than that of nonusers (p = 0.021) in the matched cohort. Users of hydrophilic statins, but not lipophilic ones had a significantly longer RFS than nonusers. Multivariable analysis showed that statin use significantly improved RFS (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.17-0.97, p = 0.044). No difference was seen in RFS between metformin users and nonusers. Among patients with diabetes, RFS was nonsignificantly longer in metformin users than in non-metformin users (84.1% vs. 60.85%, p = 0.069) in the matched cohort. No difference in postoperative RFS was seen between aspirin users and nonusers. CONCLUSION: Preoperative use of statins in patients with HCC can increase RFS after curative liver resection, but metformin and aspirin were not associated with improved survival. Randomized controlled trials are needed to confirm the findings of the present study.


Assuntos
Carcinoma Hepatocelular , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Hepáticas , Metformina , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Metformina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Pontuação de Propensão , Aspirina/efeitos adversos , Estudos Retrospectivos , Hepatectomia/efeitos adversos
10.
Sci Rep ; 13(1): 14548, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37666916

RESUMO

Autonomic symptoms (AS) are critical in Parkinson's disease (PD). We aimed to determine the relative significance of clinical factors allowing predictions about incidence of AS, and examine AS profiles among PD patients by motor subtype and its relation to AS. The cross-sectional data of a multicentre sample, including 714 PD patients and 194 healthy controls from Parkinson's Progression Marker Initiative study and Pingchan granule study were analyzed, stratified by PD subtypes [postural instability and gait disturbances (PIGD), tremor dominant (TD), and indeterminate] and domain autonomic dysfunction. Compared with healthy controls, PD patients scored higher in the total Scales for Outcomes in Parkinson's Disease-Autonomic dysfunction score and in several domain scores in particular, and there was a significant overlap in domain AS. Risk factors of individual domain autonomic dysfunction were heterogeneous. PIGD and indeterminate were the predominant subtypes in pupillomotor and thermoregulatory symptoms. TD and indeterminate were more likely to suffer from cardiovascular problem. The odd in sexual dysfunction was significant for PIGD. Gastrointestinal and urinary symptoms seemed not to be associated with a specific subtype. Our study demonstrated that AS were highly heterogeneous and 3 subtypes differed in autonomic performance, providing clues to understand mechanisms underlying AS in PD.


Assuntos
Doença de Parkinson , Disautonomias Primárias , Humanos , Estudos Transversais , Tremor , Sistema Nervoso Autônomo
11.
Biomedicines ; 11(8)2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37626693

RESUMO

To improve the survival of patients with hepatocellular carcinoma (HCC), new biomarkers and therapeutic targets are urgently needed. In this study, the GEO and TCGA dataset were used to explore the differential co-expressed genes and their prognostic correlation between HCC and normal samples. The mRNA levels of these genes were validated by qRT-PCR in 20 paired fresh HCC samples. The results demonstrated that the eight-gene model was effective in predicting the prognosis of HCC patients in the validation cohorts. Based on qRT-PCR results, NOX4 was selected to further explore biological functions within the model and 150 cases of paraffin-embedded HCC tissues were scored for NOX4 immunohistochemical staining. We found that the NOX4 expression was significantly upregulated in HCC and was associated with poor survival. In terms of function, the knockdown of NOX4 markedly inhibited the progression of HCC in vivo and in vitro. Mechanistic studies suggested that NOX4 promotes HCC progression through the activation of the epithelial-mesenchymal transition. In addition, the sensitivity of HCC cells to sorafenib treatment was obviously decreased after NOX4 overexpression. Taken together, this study reveals NOX4 as a potential therapeutic target for HCC and a biomarker for predicting the sorafenib treatment response.

12.
Virol J ; 20(1): 189, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620959

RESUMO

BACKGROUND: The emergence of COVID-19 and the implementation of preventive measures and behavioral changes have led to a significant decrease in the prevalence of other respiratory viruses. However, the manner in which seasonal viruses will reemerge in the absence of COVID-19-related restrictions remains unknown. METHODS: Patients presenting with influenza-like illness in two hospitals in Beijing were subjected to testing for COVID-19, influenza A, and influenza B to determine the causative agent for viral infections. The prevalence of influenza B across China was confirmed using data from the Centers for Disease Control, China (China CDC). Clinical characteristics, laboratory findings, imaging results, and mortality data were collected for a cohort of 70 hospitalized patients with confirmed influenza B from 9 hospitals across China. RESULTS: Starting from October 2021, a substantial increase in the number of patients visiting the designated fever clinics in Beijing was observed, with this trend continuing until January 2022. COVID-19 tests conducted on these patients yielded negative results, while the positivity rate for influenza rose from approximately 8% in October 2021 to over 40% by late January 2022. The cases started to decline after this peak. Data from China CDC confirmed that influenza B is a major pathogen during the season. Sequencing of the viral strain revealed the presence of the Victoria-like lineage of the influenza B strain, with minor variations from the Florida/39/2018 strain. Analysis of the hospitalized patients' characteristics indicated that severe cases were relatively more prevalent among younger individuals, with an average age of 40.9 ± 24.1 years. Among the seven patients who succumbed to influenza, the average age was 30 ± 30.1 years. These patients exhibited secondary infections involving either bacterial or fungal pathogens and displayed elevated levels of cell death markers (such as LDH) and coagulation pathway markers (D-dimer). CONCLUSION: Influenza B represents a significant infection threat and can lead to substantial morbidity and mortality, particularly among young patients. To mitigate morbidity and mortality rates, it is imperative to implement appropriate vaccination and other preventive strategies.


Assuntos
COVID-19 , Influenza Humana , Humanos , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Idoso , Influenza Humana/epidemiologia , COVID-19/epidemiologia , Estações do Ano , Teste para COVID-19 , China/epidemiologia
13.
Front Immunol ; 14: 1116131, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37646038

RESUMO

An unprecedented global pandemic caused by a novel coronavirus named SARS-CoV-2 has created a severe healthcare threat and become one of the biggest challenges to human health and the global economy. As of July 2023, over 767 million confirmed cases of COVID-19 have been diagnosed, including more than 6.95 million deaths. The S protein of this novel coronavirus binds to the ACE2 receptor to enter the host cells with the help of another transmembrane protease TMPRSS2. Infected subjects that can mount an appropriate host immune response can quickly inhibit the spread of infection into the lower respiratory system and the disease may remain asymptomatic or a mild infection. The inability to mount a strong initial response can allow the virus to replicate unchecked and manifest as severe acute pneumonia or prolonged disease that may manifest as systemic disease manifested as viremia, excessive inflammation, multiple organ failure, and secondary bacterial infection among others, leading to delayed recovery, hospitalization, and even life-threatening consequences. The clinical management should be targeted to specific pathogenic mechanisms present at the specific phase of the disease. Here we summarize distinct phases of COVID-19 pathogenesis and appropriate therapeutic paradigms associated with the specific phase of COVID-19.


Assuntos
COVID-19 , Coinfecção , Humanos , SARS-CoV-2 , Endopeptidases , Hospitalização
14.
Radiology ; 308(2): e230457, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37642572

RESUMO

Background Hepatocellular carcinomas (HCCs) can be divided into proliferative and nonproliferative types, which may have implications for outcomes after conventional transarterial chemoembolization (cTACE). Biopsy to identify proliferative HCC is not routinely performed before cTACE. Purpose To develop and validate a predictive model for identifying proliferative HCCs using CT imaging features and to compare therapeutic outcomes between predicted proliferative and nonproliferative HCCs after cTACE according to this model. Materials and Methods This retrospective multicenter study included adults with HCC who underwent liver resection or cTACE between August 2013 and December 2020. A CT-based predictive model for identifying proliferative HCCs was developed and externally validated in a cohort that underwent resection. Diagnostic performance was calculated for the model. Thereafter, patients in the cTACE cohort were stratified into groups with predicted proliferative or nonproliferative HCCs according to the model. The primary outcome was overall survival (OS), and the secondary outcomes were tumor response rate and progression-free survival (PFS). These were compared between the two groups with use of the χ2 test and the log-rank test. Results A total of 1194 patients (1021 men; mean age, 54 years ± 12 [SD]; median follow-up time, 29.1 months) were included. The predictive model, named the SMARS score, incorporated lobulated shape, mosaic architecture, α-fetoprotein levels, rim arterial phase hyperenhancement, and satellite lesions. The area under the receiver operating characteristic curve for the SMARS score was 0.83 for the training cohort and 0.80 for the validation cohort. According to the SMARS score, patients with predicted proliferative HCCs (n = 114) had lower tumor response rate (48% vs 71%; P < .001) and worse PFS (6.6 months vs 12.4 months; P < .001) and OS (14.4 months vs 38.7 months; P < .001) than those with nonproliferative HCCs (n = 263). Conclusion The predictive model demonstrated good performance for identifying proliferative HCCs. According to the SMARS score, patients with predicted proliferative HCCs have worse prognosis than those with predicted nonproliferative HCCs after cTACE. © RSNA, 2023 Supplemental material is available for this article.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Intervalo Livre de Progressão , Tomografia Computadorizada por Raios X
16.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(3): 454-463, 2023 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-37407534

RESUMO

So far,the coronavirus disease 2019(COVID-19)has been persisting for nearly three years,infecting about 700 million people and causing more than 6 million deaths,which has seriously affected the human society.According to Global Initiative on Sharing All Influenza Data,there are more than 12 million SARS-CoV-2 variants,of which the five major variants of concern are Alpha,Beta,Gamma,Delta and Omicron.Their infectivity,pathogencity,and neutralization resistance have changed greatly compared with the original strain,which has brought great pressure to the prevention and control of the pandemic.Antibody level testing is critical for confirming infection,epidemiological investigation,vaccine development,and neutralizing drug preparation.Focusing on the humoral immunity against SARS-CoV-2,this paper introduces the mutation sites,neutralization resistance,and vaccination efficacy of the five variants of concern,and briefly summarizes the evolutionary characteristics,future mutation directions,and host immunity.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Formação de Anticorpos , Raios gama , Anticorpos Neutralizantes , Anticorpos Antivirais
17.
Cell Death Dis ; 14(7): 431, 2023 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-37452033

RESUMO

Pancreatic cancer is a leading cause of cancer death due to its early metastasis and limited response to the current therapies. Metastasis is a complicated multistep process, which is determined by complex genetic alterations. Despite the identification of many metastasis-related genes, distinguishing the drivers from numerous passengers and establishing the causality in cancer pathophysiology remains challenging. Here, we established a high-throughput and piggyBac transposon-based genetic screening platform, which enables either reduced or increased expression of chromosomal genes near the incorporation site of the gene search vector cassette that contains a doxycycline-regulated promoter. Using this strategy, we identified YWHAZ as a key regulator of pancreatic cancer metastasis. We demonstrated that functional activation of Ywhaz by the gene search vector led to enhanced metastatic capability in mouse pancreatic cancer cells. The metastasis-promoting role of YWHAZ was further validated in human pancreatic cancer cells. Overexpression of YWHAZ resulted in more aggressive metastatic phenotypes in vitro and a shorter survival rate in vivo by modulating epithelial-to-mesenchymal transition. Hence, our study established a high-throughput screening method to investigate the functional relevance of novel genes and validated YWHAZ as a key regulator of pancreatic cancer metastasis.


Assuntos
Neoplasias Pancreáticas , Animais , Camundongos , Humanos , Neoplasias Pancreáticas/patologia , Linhagem Celular Tumoral , Metástase Neoplásica , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Neoplasias Pancreáticas
18.
Chirurgie (Heidelb) ; 94(8): 696-702, 2023 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-37470862

RESUMO

Vascular injuries and hemorrhaging are serious potential complications in the management of patients with blunt abdominal trauma. The treatment depends on the extent and localization and can range from surveillance to endovascular treatment up to open surgery. The keys to success include the focused assessment with sonography for trauma (FAST) management and timely decision making. Abdominal vascular trauma continues to be a difficult problem and open and endovascular techniques continue to evolve in order to address this complex disease process.


Assuntos
Cavidade Abdominal , Traumatismos Abdominais , Procedimentos Endovasculares , Avaliação Sonográfica Focada no Trauma , Lesões do Sistema Vascular , Ferimentos não Penetrantes , Humanos , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/cirurgia , Procedimentos Endovasculares/efeitos adversos , Traumatismos Abdominais/diagnóstico por imagem , Traumatismos Abdominais/cirurgia , Traumatismos Abdominais/etiologia , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/cirurgia
19.
Discov Oncol ; 14(1): 133, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37470865

RESUMO

PURPOSE: Prostate cancer (PCa) with high Ki-67 expression and high Gleason Scores (GS) tends to have aggressive clinicopathological characteristics and a dismal prognosis. In order to predict the Ki-67 expression status and the GS in PCa, we sought to construct and verify MRI-based radiomics signatures. METHODS AND MATERIALS: We collected T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) images from 170 PCa patients at three institutions and extracted 321 original radiomic features from each image modality. We used support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) logistic regression to select the most informative radiomic features and built predictive models using up sampling and feature selection techniques. Using receiver operating characteristic (ROC) analysis, the discriminating power of this feature was determined. Subsequent decision curve analysis (DCA) assessed the clinical utility of the radiomic features. The Kaplan-Meier (KM) test revealed that the radiomics-predicted Ki-67 expression status and GS were prognostic factors for PCa survival. RESULT: The hypothesized radiomics signature, which included 15 and 9 selected radiomics features, respectively, was significantly correlated with pathological Ki-67 and GS outcomes in both the training and validation datasets. Areas under the curve (AUC) for the developed model were 0.813 (95% CI 0.681,0.930) and 0.793 (95% CI 0.621, 0.929) for the training and validation datasets, respectively, demonstrating discrimination and calibration performance. The model's clinical usefulness was verified using DCA. In both the training and validation sets, high Ki-67 expression and high GS predicted by radiomics using SVM models were substantially linked with poor overall survival (OS). CONCLUSIONS: Both Ki-67 expression status and high GS correlate with PCa patient survival outcomes; therefore, the ability of the SVM classifier-based model to estimate Ki-67 expression status and the Lasso classifier-based model to assess high GS may enhance clinical decision-making.

20.
Chronic Dis Transl Med ; 9(2): 104-121, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37305112

RESUMO

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease and the third leading cause of death worldwide. Developments in next-generation sequencing technology have improved microbiome analysis, which is increasingly recognized as an important component of disease management. Similar to the gut, the lung is a biosphere containing billions of microbial communities. The lung microbiome plays an important role in regulating and maintaining the host immune system. The microbiome composition, metabolites of microorganisms, and the interactions between the lung microbiome and the host immunity profoundly affect the occurrence, development, treatment, and prognosis of COPD. In this review, we drew comparisons between the lung microbiome of healthy individuals and that of patients with COPD. Furthermore, we summarize the intrinsic interactions between the host and the overall lung microbiome, focusing on the underlying mechanisms linking the microbiome to the host innate and adaptive immune response pathways. Finally, we discuss the possibility of using the microbiome as a biomarker to determine the stage and prognosis of COPD and the feasibility of developing a novel, safe, and effective therapeutic target.

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