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1.
Artigo em Inglês | MEDLINE | ID: mdl-37851319

RESUMO

Extracellular vesicles (EVs) are small lipid bilayer-enclosed vesicles that mediate vital cellular communication by transferring cargo between cells. Among these, tissue-derived extracellular vesicles (Ti-EVs) stand out due to their origin from the tissue microenvironment, providing a more accurate reflection of changes in this setting. This unique advantage makes Ti-EVs valuable in investigating the intricate relationship between extracellular vesicles and cancer progression. Despite considerable research efforts exploring the association between Ti-EVs and cancers, a comprehensive clustering or grouping of these studies remains lacking. In this review, we aim to fill this gap by presenting a comprehensive synthesis of the mechanisms underlying Ti-EV generation, release, and transport within cancer tissues. Moreover, we delve into the pivotal roles that Ti-EVs play in cancer progression, shedding light on their potential as diagnostic and therapeutic tools. The review culminates in the construction of a comprehensive functional spectrum of Ti-EVs, providing a valuable reference for future research endeavors. By summarizing the current state of knowledge on Ti-EVs and their significance in tumor biology, this work contributes to a deeper understanding of cancer microenvironment dynamics and opens up avenues for harnessing Ti-EVs in diagnostic and therapeutic applications.

2.
Br J Cancer ; 130(6): 925-933, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38238428

RESUMO

BACKGROUND: The diagnosis of follicular thyroid carcinoma (FTC) prior to surgery remains a major challenge in the clinic. METHODS: This multicentre diagnostic study involved 41 and 150 age- and sex-matched patients in the training cohort and validation cohort, respectively. The diagnostic properties of circulating small extracellular vesicle (sEV)-associated and cell-free RNAs were compared by RNA sequencing in the training cohort. Subsequently, using a quantitative real-time polymerase chain reaction (qRT‒PCR) assay, high-quality candidates were identified to construct an RNA classifier for FTC and verified in the validation cohort. The parallel expression, stability and influence of the RNA classifier on surgical strategy were also investigated. RESULTS: The diagnostic properties of sEV long RNAs, cell-free long RNAs and sEV microRNAs (miRNAs) were comparable and superior to those of cell-free miRNAs in RNA sequencing. Given the clinical application, the circulating sEV miRNA (CirsEV-miR) classifier was developed from five miRNAs based on qRT‒PCR data, which could well identify FTC patients (area under curve [AUC] of 0.924 in the training cohort and 0.844 in the multicentre validation cohort). Further tests revealed that the CirsEV-miR score was significantly correlated with the tumour burden, and the levels of sEV miRNAs were also higher in sEVs from the FTC cell line, organoid and tissue. Additionally, circulating sEV miRNAs remained constant after different treatments, and the addition of the CirsEV-miR classifier as a biomarker improves the current surgical strategy. CONCLUSIONS: The CirsEV-miR classifier could serve as a noninvasive, convenient, specific and stable auxiliary test to help diagnose FTC following ultrasonography.


Assuntos
Adenocarcinoma Folicular , Vesículas Extracelulares , MicroRNAs , Neoplasias da Glândula Tireoide , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/metabolismo , Biomarcadores , Vesículas Extracelulares/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo
3.
Mol Cancer ; 22(1): 193, 2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-38037077

RESUMO

Current research has demonstrated that extracellular vesicles (EVs) and circulating tumor cells (CTCs) are very closely related in the process of distant tumor metastasis. Primary tumors are shed and released into the bloodstream to form CTCs that are referred to as seeds to colonize and grow in soil-like distant target organs, while EVs of tumor and nontumor origin act as fertilizers in the process of tumor metastasis. There is no previous text that provides a comprehensive review of the role of EVs on CTCs during tumor metastasis. In this paper, we reviewed the mechanisms of EVs on CTCs during tumor metastasis, including the ability of EVs to enhance the shedding of CTCs, protect CTCs in circulation and determine the direction of CTC metastasis, thus affecting the distant metastasis of tumors.


Assuntos
Vesículas Extracelulares , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patologia , Metástase Neoplásica/patologia , Biomarcadores Tumorais
4.
BMC Med ; 21(1): 206, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280674

RESUMO

BACKGROUND: Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disease characterized by lymphocyte infiltration that destroys thyrocyte cells. The aim of the present study was to elucidate the role and mechanisms of tissue small extracellular vesicle (sEV) microRNAs (miRNAs) in the pathogenesis of HT. METHODS: Differentially expressed tissue sEV miRNAs were identified between HT tissue and normal tissue by RNA sequencing in the testing set (n = 20). Subsequently, using quantitative real-time polymerase chain reaction (qRT‒PCR) assays and logistic regression analysis in the validation set (n = 60), the most relevant tissue sEV miRNAs to HT were verified. The parental and recipient cells of that tissue sEV miRNA were then explored. In vitro and in vivo experiments were further performed to elucidate the function and potential mechanisms of sEV miRNAs that contribute to the development of HT. RESULTS: We identified that miR-142-3p encapsulated in T lymphocyte-derived tissue sEVs can induce Treg function defect and thyrocyte destruction through an intact response loop. Inactivation of miR-142-3p can effectively protect non-obese diabetic (NOD).H-2h4 mice from HT development display reduced lymphocyte infiltration, lower antibody titers, and higher Treg cells. Looking at the mechanisms underlying sEV action on thyrocyte destruction, we found that the strong deleterious effect mediated by tissue sEV miR-142-3p is due to its ability to block the activation of the ERK1/2 signaling pathway by downregulating RAC1. CONCLUSIONS: Our findings highlight the fact that tissue sEV-mediated miR-142-3p transfer can serve as a communication mode between T lymphocytes and thyrocyte cells in HT, favoring the progression of HT.


Assuntos
Vesículas Extracelulares , MicroRNAs , Células Epiteliais da Tireoide , Tireoidite , Camundongos , Animais , Células Epiteliais da Tireoide/metabolismo , Linfócitos T Reguladores , Camundongos Endogâmicos NOD , MicroRNAs/genética , MicroRNAs/metabolismo , Vesículas Extracelulares/metabolismo
5.
Clin Endocrinol (Oxf) ; 98(5): 709-718, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36394172

RESUMO

OBJECTIVE: To evaluate the diagnostic performance and cost-effectiveness of calcitonin assays in fine-needle aspiration washout fluid (FNA-CT) compared to fine-needle aspiration cytology (FNAC) for medullary thyroid carcinoma (MTC). METHODS: A total of 27,404 patients from three medical centres between January 2020 and May 2022 were screened for serum calcitonin (sCT). Of whom, 223 patients met endpoints and were enroled for analyses. Based on sCT levels, patients were divided into two groups (group 1: 10 pg/ml< sCT ≤100 pg/ml and group 2: sCT > 100 pg/ml). The diagnostic performance and cost-effectiveness of FNA-CT and FNAC were compared. RESULTS: Most patients (N = 25,228; 92.1%) with thyroid nodules had normal sCT levels. In group 1, 24 and 167 nodules were diagnosed as MTC and non-MTC lesions, respectively. FNA-CT showed better performance in diagnosing MTC than FNAC in terms of sensitivity (100.0% vs. 58.3%), negative predictive value (100.0% vs. 94.3%), and overall accuracy (100.0% vs. 94.7%). In group 2, 67 and 7 nodules were diagnosed as MTC and non-MTC lesions, respectively. The diagnostic performance of FNA-CT was superior to FNAC in terms of sensitivity (100.0% vs. 64.2%), negative predictive value (100.0% vs. 22.6%), and overall accuracy (100.0% vs. 67.6%). Furthermore, analysis from the decision tree model showed that FNA-CT was a cost-effective tool for diagnosing MTC lesions. CONCLUSIONS: FNA-CT can serve as an auxiliary and cost-effective approach for patients with indeterminate sCT levels to detect occult MTC lesions. FNA-CT can be recommended for patients with sCT >100 pg/ml to overcome the high false-negative rate of FNAC.


Assuntos
Conservadores da Densidade Óssea , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Calcitonina/análise , Análise Custo-Benefício , Biópsia por Agulha Fina , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Hormônios e Agentes Reguladores de Cálcio , Tomografia Computadorizada por Raios X
6.
J Med Internet Res ; 25: e47912, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37796623

RESUMO

BACKGROUND: In recent years, the new generation of telecommunication technologies has profoundly changed the traditional medical industry. To alleviate the medical difficulties faced by patients with thyroid diseases, hospitals have opened web-based visits and actively combined online-to-offline outpatient services. OBJECTIVE: This study aims to explore differences between office and web-based outpatient services from doctors' and patients' perspectives, illustrate the effect of the COVID-19 pandemic on outpatient services, and provide clues for improving the online-to-offline mode of care for patients with thyroid diseases. METHODS: We collected the complete web-based and office outpatient records of the Thyroid Surgery Center of West China Hospital. A total of 300,884 completed patient encounters occurred (201,840 office visits and 99,044 web-based visits) from January 1, 2019, to May 31, 2022. We performed logistic regression to evaluate the association between the chosen visit type and patients' sociodemographic characteristics. RESULTS: The number of web-based visits rapidly increased since March 2020 and reached 45.1% (4752/10,531) of all encounters in December 2021. The COVID-19 pandemic dramatically accelerated the development of web-based visits. Web-based visits were preferred by patients 18-45 years old (odds ratio [OR] 2.043, 95% CI 1.635-2.552, P<.001), patients with relatively high-paying jobs (technical staff: OR 1.278, 95% CI 1.088-1.479, P=.003; office clerk: OR 1.25, 95% CI 1.07-1.461, P=.005; national public servant: OR:1.248, 95% CI 1.042-1.494, P=.02), and patients living in Sichuan Province (excluding Chengdu; OR 1.167, 95% CI 1.107-1.23, P<.001). The medicine cost (P<.001) and examination cost (P<.001) of office visits were significantly higher than those of web-based visits. CONCLUSIONS: Web-based outpatient visits have increased rapidly in recent years, and the COVID-19 pandemic has boosted their development. The preference for web-based visits was influenced by the socioeconomic and demographic characteristics of both patients and doctors.


Assuntos
COVID-19 , Doenças da Glândula Tireoide , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Transversais , Pandemias , Internet
7.
Int J Mol Sci ; 24(18)2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37762070

RESUMO

Thyroid cancer has become more common in recent years all around the world. Many issues still need to be urgently addressed in the diagnosis, treatment, and prognosis of thyroid cancer. Liquid biopsy (mainly circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and circulating exosomes) may provide a novel and ideal approach to solve these issues, allows us to assess the features of diseases more comprehensively, and has a function in a variety of malignancies. Recently, liquid biopsy has been shown to be critical in thyroid cancer diagnosis, treatment, and prognosis in numerous previous studies. In this review, by testing CTCs, ctDNA, and exosomes, we focus on the possible clinical role of liquid biopsy in thyroid cancer, including diagnostic and prognostic biomarkers and response to therapy. We briefly review how liquid biopsy components have progressed in thyroid cancer by consulting the existing public information. We also discuss the clinical potential of liquid biopsy in thyroid cancer and provide a reference for liquid biopsy research. Liquid biopsy has the potential to be a useful tool in the early detection, monitoring, or prediction of response to therapies and prognosis in thyroid cancer, with promising clinical applications.


Assuntos
Exossomos , Neoplasias da Glândula Tireoide , Humanos , Exossomos/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , DNA de Neoplasias , Biópsia Líquida
8.
Clin Endocrinol (Oxf) ; 97(5): 676-684, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35261045

RESUMO

BACKGROUND: The eighth edition of the American Joint Committee on Cancer tumour, node, and metastasis staging system did not take T stage into consideration when evaluating Stage IV C medullary thyroid carcinoma (MTC) patients. The aim of this study is to investigate the clinical outcomes and implications of T stage in this population. METHODS: Eligible patients from the Surveillance, Epidemiology, and End Results database and the Department of Thyroid Surgery in West China Hospital of Sichuan University and who were diagnosed with Stage IV C MTC were included in this study. The overall survival (OS), the cancer-specific survival (CSS), and the precise cause of MTC-induced death were analysed. The potential risk factors, including the T stage, in the OS and CSS were evaluated by univariate and multivariate Cox regression models. RESULTS: This retrospective study enroled 204 Stage IV C MTC patients. The 5- and 10-year OS rates were 31.8% and 17.1%, respectively, and the 5- and 10-year CSS rates were 40.4% and 22.5%, respectively. More importantly, the rates of MTC-induced death between primary or distant metastatic lesions in Stage IV C MTC patients were comparable in our institution. Additionally, the univariate and multivariate analyses demonstrated that the presence of an advanced T stage was an independent prognostic factor for both the OS (T4 vs. T1-T3, hazard ratio [HR]: 1.714, 95% confidence interval [CI]: 1.175-2.500, p = .005) and the CSS (T4 vs. T1-T3, HR: 1.848, 95% CI: 1.229-2.780, p = .003). CONCLUSION: To achieve a better risk stratification, further classification of Stage IV C MTC patients by the T stage may be preferable.


Assuntos
Neoplasias da Glândula Tireoide , Carcinoma Neuroendócrino , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia
9.
BMC Surg ; 21(1): 317, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344330

RESUMO

OBJECTIVE: Microwave ablation (MWA) is a minimally invasive technique for the treatment of benign thyroid nodules. The purpose of this study was to evaluate efficacy and safety of ultrasound-guided MWA in the treatment of benign thyroid nodules, and to find out the recurrence related factors, so as to provide reference for future clinical work. METHODS: This study retrospectively analyzed the patients who received ultrasound-guided MWA for benign thyroid nodules in our hospital from October 2018 to March 2020. A total of 214 patients were included in the study. We assessed thyroid volume changes (represented by volume reduction ratio VRR), the energy per 1 mL reduction in nodular volume (represented by energy volume ratio ΔE), the serum levels of free triiodide thyroid hormone (FT3), free thyroxine (FT4), thyrotropin (TSH) and complications after MWA treatment. RESULTS: There were a total of 306 nodules in 214 patients, including 183 (85.51%) females and 31 (14.49%) males. The median diameter and volume of the nodule were 33 mm and 8.01 mL. The VRR at 1 month, 3 months, 6 months and 12 months were 40.79%, 60.37%, 74.59% and 85.60%, respectively. In addition, MWA had a better ablation effect for small nodules (initial volume ≤ 10 mL). In recurrent studies, we found that ΔE was an independent risk factor for benign thyroid nodules (P < 0.05). CONCLUSIONS: Ultrasound-guided MWA is effective and safe in the treatment of benign thyroid nodules. In addition, it has little damage to surrounding tissues and no effect on thyroid function. Especially, the nodules with smaller initial volume, the treatment is better. On the other hand, the energy per 1 mL reduction ΔE in nodular volume may be associated with nodular recurrence, which requires further follow-up for longer periods. At this stage, we consider that ultrasound-guided MWA can be used as one of the main clinical treatment methods for benign thyroid nodules.


Assuntos
Ablação por Cateter , Nódulo da Glândula Tireoide , Feminino , Humanos , Masculino , Micro-Ondas , Recidiva Local de Neoplasia , Estudos Retrospectivos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/cirurgia , Resultado do Tratamento , Ultrassonografia de Intervenção
10.
Am J Transplant ; 18(7): 1668-1679, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29232038

RESUMO

Ex vivo liver resection combined with autotransplantation is a recently introduced approach to cure end-stage hepatic alveolar echinococcosis (HAE), which is considered unresectable by conventional radical resection due to echinococcal dissemination into the crucial intrahepatic conduits and adjacent structures. This article aims discuss the manipulation details and propose reasonable indications for this promising technique. All patients successfully underwent liver autotransplantation with no intraoperative mortality. The median weight of the autografts was 636 g (360-1300 g), the median operation time was 12.5 hours (9.4-19.5 hours), and the median anhepatic phase was 309 minutes (180- 460 minutes). Intraoperative blood loss averaged 1800 mL (1200-6000 mL). Postoperative complications occurred in 13 patients during hospitalization; 5 patients experienced postoperative complications classified as Clavien-Dindo grade III or higher, and 2 patients died of intraabdominal bleeding and acute cerebral hemorrhage, respectively. Twenty-nine patients were followed for a median of 14.0 months (3-42 months), and no HAE recurrence was detected. The technique requires neither an organ donor nor any postoperative immunosuppressant, and the success of the treatment relies on meticulous preoperative assessments and precise surgical manipulation.


Assuntos
Equinococose Hepática/cirurgia , Rejeição de Enxerto/etiologia , Hepatectomia/efeitos adversos , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias , Adolescente , Adulto , Equinococose Hepática/patologia , Feminino , Seguimentos , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Transplante Autólogo , Adulto Jovem
11.
Cytopathology ; 29(6): 525-530, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30238537

RESUMO

AIMS: Conventional smears (CS) of samples obtained by fine needle aspiration (FNA) have proven useful in thyroid nodules evaluation, but the additional contribution of cell block (CB) has only been investigated in a limited fashion. In this study, we aimed to evaluate whether the auxiliary application of CB adds to the diagnostic accuracy of the CS by a College of American Pathologists-accredited hospital laboratory. METHODS: All thyroid FNA samples processed with CS only or combined CB and CS in West China Hospital from January 2011 to December 2015 were retrospectively collected. All specimens were classified according to Bethesda System, and the distribution of Bethesda (2009) categories was compared between CS and combined CS and CB. Further, we compared the diagnostic performance between these two groups for nodules with follow-up histopathology. RESULTS: A total of 11 011 thyroid nodules from 10 206 patients were included. Of these, 2395 nodules from 2211 patients underwent surgical resection. The unsatisfactory rate decreased significantly from 18.1% to 9.8% in the total group and from 1.7% to 0.8% in the group with surgery after combined use of CS and CB. The proportion of atypia/follicular lesion of undetermined significance also declined slightly. Furthermore, all of the sensitivities, specificities, accuracies and positive predictive values increased significantly after the combined use of CS and CB for different calculation methods. CONCLUSIONS: Combined use of CS and CB can significantly decrease the unsatisfactory rate of thyroid FNAs, improve the diagnostic efficacy, and thus should be routinely applied in thyroid nodule evaluation if available.


Assuntos
Biópsia por Agulha Fina/métodos , Glândula Tireoide/patologia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/patologia
12.
J Surg Oncol ; 116(3): 281-287, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28556902

RESUMO

BACKGROUND: The significance of inflammation based scores including the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and plasma fibrinogen remains unclear in medullary thyroid carcinoma (MTC). We aimed to compare the prognostic value of these scores. METHODS: Seventy-eight patients newly diagnosed as MTC with operation in our institution from May 2009 to September 2016 were retrospectively evaluated. Receiver operating characteristic (ROC) curves and Kaplan-Meier analyses were calculated to compare the prognostic value of these scores. RESULTS: Increased PLR was predictive of lymph node metastasis (AUC = 0.644, P = 0.022), capsule invasion (AUC = 0.666, P = 0.007), advanced tumor stages (AUC = 0.657, P = 0.011), and recurrence (AUC = 0.655, P = 0.049). Increased fibrinogen was predictive of lymph node metastasis (AUC = 0.669, P = 0.006) and capsule invasion (AUC = 0.631, P = 0.038). Reduced PNI was predictive of recurrence (AUC = 0.655, P = 0.049). Kaplan-Meier analyses and Cox regression analysis revealed that PLR was a significant predictor for recurrence. CONCLUSIONS: PLR, fibrinogen, and PNI are all predictive. Specially, PLR is superior to other inflammation based scores in terms of prognostic ability.


Assuntos
Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/diagnóstico , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Contagem de Células Sanguíneas , Carcinoma Neuroendócrino/mortalidade , Feminino , Fibrinogênio/metabolismo , Humanos , Inflamação , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estado Nutricional , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/mortalidade
13.
Proc Natl Acad Sci U S A ; 109(40): 16282-7, 2012 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-22988121

RESUMO

An attractive strategy to overcome multidrug resistance in cancer chemotherapy is to suppress P-glycoprotein (P-gp), which is a pump overproduced in cancer cells to remove cytotoxic drugs from cells. In the present study, a Ca(2+)-permeable channel TRPC5 was found to be overproduced together with P-gp in adriamycin-resistant breast cancer cell line MCF-7/ADM. Suppressing TRPC5 activity/expression reduced the P-gp induction and caused a remarkable reversal of adriamycin resistance in MCF-7/ADM. In an athymic nude mouse model of adriamycin-resistant human breast tumor, suppressing TRPC5 decreased the growth of tumor xenografts. Nuclear factor of activated T cells isoform c3 (NFATc3) was the transcriptional factor that links the TRPC5 activity to P-gp production. Together, we demonstrated an essential role of TRPC5-NFATc3-P-gp signaling cascade in P-gp induction in drug-resistant cancer cells.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Neoplasias da Mama/metabolismo , Resistência a Múltiplos Medicamentos/fisiologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Fatores de Transcrição NFATC/metabolismo , Transdução de Sinais/fisiologia , Canais de Cátion TRPC/metabolismo , Animais , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina , Feminino , Humanos , Luciferases , Células MCF-7 , Camundongos , Camundongos Nus , Técnicas de Patch-Clamp
14.
J Ind Microbiol Biotechnol ; 41(1): 135-42, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24174213

RESUMO

Recombinant human interleukin 24 (rhIL24) is a member of the interleukin 10 (IL10) family of cytokines with novel therapeutic properties. Human IL24 possesses three N glycosylation sites and a disulfide bridge. The cost and composition of culture media is critical for commercial-scale production of recombinant proteins in E. coli. Addition of yeast extract and glucose to medium enhances rhIL24 production, and the use of lactose instead of IPTG for induction drops the cost and decreases toxicity. In addition, a two-step denaturing and one-step refolding (2DR) strategy improves rhIL24 production. The 2DR strategy replaces a more conventional approach for protein solubilization and refolding. LC-MS/MS provides definitive identification and quantitative information on rhIL24. Single-step purified rhIL24 displayed biological activity on HepG2 hepatocellular carcinoma cells, but no effect on L02 cells. Proliferation analysis suggests that rhIL24 may have potential use as a medication. In the present study, we developed a simple process for producing quality product with high purity. The expression and purification of rhIL24 described here may be a step towards inexpensive large-scale production.


Assuntos
Interleucinas/biossíntese , Lactose/metabolismo , Linhagem Celular Tumoral , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Interleucinas/genética , Interleucinas/farmacologia , Desnaturação Proteica , Redobramento de Proteína , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/economia , Proteínas Recombinantes/farmacologia , Espectrometria de Massas em Tandem
15.
Hepatogastroenterology ; 61(132): 966-71, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26158150

RESUMO

BACKGROUND/AIMS: We evaluated the effectiveness of various therapies to treat the traumatic splenic rupture by using data from our single center. METHODOLOGY: From July 2008 to Jan 2014, 125 patients who were diagnosis spleen rupture without other organ injury were included into our present study. We divided these patients into two groups according to the managements of the splenic rupture: the operative management (OM) group (48 patients) and the non-operative management (NOM) group (77 patients). We compared the baseline characteristics and long-term outcomes of two groups. the OM group was divided into three sub-groups according to the different operative methods: the total splenectomy group, partial splenectomy group and radiofrequency ablation (RFA) group. RESULTS: Splenic injuries were most commonly observed in abdominal trauma: traffic accidents (49 cases), fall from height (36 cases), strike (22 cases), assaults (11 cases), and sports (7 cases). Of the patients included in our study, 48 patients accepted OM, and 77 patients accepted NOM. The baseline characteristics, including age, gender, BMI, and underlying diseases, were comparable between the two groups. However, the OM group patients exhibited more severe splenic rupture according to the AAST grade (P = 0.000). The three subgroups in the OM group (total splenectomies group (26 cases), partial splenectomy (12 patients), RFA-assisted spleen-preserving surgery (10 patients) exhibited no significant differences with respect to intraoperative data or postoperative recovery. The length of hospital stay in the NOM group was significantly longer than that in the OM group (6.8 ± 1.4 VS 3.4 ± 0.8, P = 0.000), but the OM and NOM patients reported comparable quality of life according to the SF-36 scale. CONCLUSION: In conclusion, the outcomes of operative management for splenic rupture were comparable, and the OM and the NOM patients exhibited a similar quality of life after splenic rupture, although longer hospital stays were observed in the NOM group.


Assuntos
Ablação por Cateter , Esplenectomia , Ruptura Esplênica/terapia , Adulto , Ablação por Cateter/efeitos adversos , China , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco , Esplenectomia/efeitos adversos , Esplenectomia/métodos , Ruptura Esplênica/diagnóstico , Ruptura Esplênica/etiologia , Ruptura Esplênica/cirurgia , Fatores de Tempo , Resultado do Tratamento
16.
Hepatogastroenterology ; 61(131): 717-21, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-26176063

RESUMO

BACKGROUND/AIMS: In this study, we try to investigate the possible causes of failed TACE when it is served as a down-staging therapy for advanced hepatocellular carcinoma. METHODOLOGY: Two hundred and seventy eight patients had diagnoses of unresectable hepatocellular carcinoma but had the possibility to accept a resection if they accepted the successful use of TACE as a down-staging therapy. The patients were divided into two groups based on the result of the down-staging therapy: those within the UCSF criteria (group 1, N = 166) and those outside of the criteria (group 2, N = 112). RESULTS: There was no significant difference between the two groups in their demographic characteristics or their liver function. There were more tumor targets in the failed group (2.5 ± 1.5) than in the successful group (2.1 ± 1.3) (P = 0.013); however, the difference in the total diameter of the targets per patient did not reach statistical significance (P = 0.321), after one to four TACE sessions, the final AFP level was significantly different between the two groups (P = 0.042); there were more patients with a post-treatment AFP level 400 ng/ml in the failed group(28.7% vs. 20.5%, P=0.042). After comparing the number of TACE sessions between two groups, no significant difference was found (P = 0.659). A logistic regression analysis revealed three independent factors that were associated with the failure of TACE when it was used as a down-staging therapy: the tumor target number, post-TACE AFP level and number of TACE sessions (P < 0.05). CONCLUSIONS: The current results indicate that post-TACE AFP ≥ 400 ng/ml and more tumor targets were the dropout factors influencing the failure of TACE when it was used as a down-staging therapy for advanced HCC patients who previously met the UCSF criteria.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Primárias Múltiplas , Pacientes Desistentes do Tratamento , Adulto , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Quimioterapia Adjuvante , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Carga Tumoral , alfa-Fetoproteínas/metabolismo
17.
Hepatobiliary Pancreat Dis Int ; 13(1): 25-31, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24463076

RESUMO

BACKGROUND: Platelet count reduction in living donors after graft harvesting is very common. The mechanisms and the subsequent adverse consequences are not clear. The present study was to explore the mechanisms and the consequences of platelet count reduction in living donors. METHODS: We collected data from 231 living liver donor patients who donated at our transplant center between July 2002 and August 2009. Baseline and post-operative platelet counts were collected and analyzed. Multivariate logistic regression analysis was used to compare the risk factors for the persistent decrease in platelet counts. Complications and other post-operative recovery were compared between the donors. RESULTS: Platelet count decreased differently at each of the follow-up intervals, and the average reduction from baseline evaluation to year 3 was 18.2%. A concomitant decrease in white blood cells was observed with platelet count reduction. All of the splenic volumes at the post-operative follow-up time points were significantly higher than those at baseline (P<0.01). Multivariate logistic regression analysis indicated that the graft-to-donor weight ratio was a risk factor for low post-operative platelet counts in living donors at the three follow-up time points: one week (P=0.047), one month (P=0.034), and three months (P=0.047). At the one week follow-up time, 77 donor platelet counts were higher (group 1) and 151 donor platelet counts were lower (group 2) than baseline levels. Two hemorrhage events (1.3%) were observed in group 2, while three hemorrhage events (3.9%) were observed in group 1 (P=0.211). The overall complication rate was comparable between the two groups (P=0.972). CONCLUSION: An increase in harvesting graft may decrease platelet counts, but this reduction does not produce short- or long-term damage in living liver donors.


Assuntos
Transplante de Fígado , Fígado/cirurgia , Doadores Vivos , Contagem de Plaquetas , Adulto , Feminino , Seguimentos , Humanos , Contagem de Leucócitos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco
18.
GMS J Med Educ ; 41(1): Doc10, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38504857

RESUMO

Objective: The outbreak of COVID-19 has disrupted social order and placed a heavy burden on the healthcare system. The pandemic also has an unprecedented impact on medical students. Methods: We searched PubMed for articles related to COVID-19 and medical students from January 2020 to December 2022. A total of 5358 studies were retrieved and after screening, 176 studies were finally included in this review. Results: The impact of COVID-19 on medical students is widespread and profound. First reflected in the transformation of educational models. In the early days, education model quickly shifted from offline to online. In terms of clinical exposure, most students have been suspended from internships, while in some areas with staff shortages they have the opportunity to continue clinical work. Scientific research of medical students is also difficult to carry out due to COVID-19. The epidemic has also seriously damaged students' mental health, and this impact won't simply disappear with the improvement of the epidemic situation. The career intentions of medical students may also become firmer or change due to COVID-19. International medical electives have also been negatively affected by COVID-19 due to travel restriction. Even in the postpandemic era, with the gradual resumption of work, production and school, medical students are still affected in some ways by COVID-19. Conclusion: The COVID-19 pandemic has had a profound impact on both the education of medical students and their personal development. Through COVID-19, we should reflect on what models of medical education should be developed in the future. Based on the experiences learned from COVID-19, we believe that a more flexible blended education model may be the most promising.


Assuntos
COVID-19 , Educação Médica , Estudantes de Medicina , Humanos , COVID-19/epidemiologia , Pandemias , Surtos de Doenças
19.
Clin Nucl Med ; 49(4): 366-368, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38389218

RESUMO

ABSTRACT: Struma ovarii is a rare form of ovarian teratoma composed entirely or mainly of mature thyroid tissue. A 55-year-old woman with persistent hypogastric pain for 4 months was admitted to our hospital. She had undergone resection of struma ovarii 4 years ago. Contrast-enhanced CT shows multiple significantly enhanced nodules scattered in the abdominopelvic cavity. Pathological examination of the nodule in the left pararenal region demonstrated thyroid-like follicular epithelium. Herein, we present the 99m TcO 4 whole-body scintigraphy SPECT/CT findings of a case of struma ovarii with extensive peritoneal implants metastasis. Then, she was treated with total thyroidectomy and 131 I therapy.


Assuntos
Neoplasias Ovarianas , Neoplasias Peritoneais , Estruma Ovariano , Teratoma , Feminino , Humanos , Pessoa de Meia-Idade , Estruma Ovariano/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico por imagem , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único
20.
J Clin Endocrinol Metab ; 109(9): 2294-2305, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-38436929

RESUMO

BACKGROUND: The clinical outcomes and implications of radioactive iodine therapy (RAIT) on cancer-specific survival (CSS) in World Health Organization classification of follicular thyroid carcinoma (FTC) are not well established. MATERIAL AND METHODS: The data of eligible patients with minimally invasive FTC (mi-FTC), encapsulated angioinvasive FTC (ea-FTC), or widely invasive FTC (wi-FTC) between 2000 and 2020 were extracted from the Surveillance, Epidemiology, and End Results database. CSS, the primary outcome, was compared among the 3 subtypes of patients with FTC before and after adjusting for differences using propensity score matching (PSM). The patients with FTC in different subtypes were then divided into 2 groups: the RAIT group and the no-RAIT group. Cox proportional hazards regression analyses were applied to discover the relationships of factors associated with CSS in the each PSM cohort. RESULTS: A total of 2433 patients with mi-FTC, 216 patients with ea-FTC, and 554 patients with wi-FTC were enrolled in the original cohorts, respectively. Patients with mi-FTC or ea-FTC had similar CSS (P = .805), which was better than that of patients with wi-FTC (P < .001; P = .021). Cox proportional hazards regression analysis revealed that RAIT was not associated with improved CSS in either the mi-FTC PSM cohort (hazard ratio [HR], 1.21; 95% CI, .46-3.18; P = .705) or the wi-FTC PSM cohort (HR, 0.56; 95% CI, .35-1.08; P = .086). However, subgroup analysis demonstrated that patients with wi-FTC and N1 stage (HR, 0.44; 95% CI, .20-.99; P = .018) or M1 stage (HR, 0.25; 95% CI, .11-.53; P < .001) could gain CSS advantage from RAIT. CONCLUSION: The RAIT can provide a CSS advantage for patients with wi-FTC who with N1-stage or M1-stage disease.


Assuntos
Adenocarcinoma Folicular , Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/radioterapia , Adenocarcinoma Folicular/mortalidade , Adenocarcinoma Folicular/patologia , Adulto , Organização Mundial da Saúde , Programa de SEER , Idoso , Resultado do Tratamento , Prognóstico , Taxa de Sobrevida , Estudos Retrospectivos
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