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1.
Thorac Cancer ; 15(3): 215-226, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38115677

RESUMO

BACKGROUND: Pyroptosis plays a pivotal role in the tumor immune microenvironment (TME) dynamics, particularly in non-small cell lung cancer (NSCLC). The aim of our study was to explore its effects on tumor progression, TME patterns, and the efficacy of therapeutic interventions in NSCLC. METHODS: Our investigation encompassed a thorough analysis of pyroptosis-related genes (PRGs), integrating immunohistochemistry (IHC) data, TME characteristics, stemness indices, and anticancer drug sensitivities. We aimed to analyze mRNA expression profiles across various cancers, constructing benchmark datasets to assess the clinical significance of PRGs in NSCLC. This included evaluating their association with clinical responses and efficacy. Notably, both our and HPA IHC data demonstrated significantly elevated GSDMD-N protein levels in lung squamous cell carcinoma (LUSC) tissues. RESULTS: The expression of PRGs differed significantly between tumor and normal tissues across various cancers, as validated by IHC data, and was correlated with prognosis (p < 0.05). Moreover, our investigation revealed significant differences (p < 0.05) in the expression of the PRGs among distinct TME subtypes categorized as C1 (wound healing), C3 (inflammatory), C2 (IFN-gamma dominant), C5 (immunological quiet), C4 (lymphocyte deficient), and C6 (TGF-beta dominant). Additionally, our research on anticancer drug sensitivity uncovered compelling connections between specific anticancer medications and the expression of PRGs, including GSDMD, ELANE, IL18, and CHMP4A (p < 0.05). CONCLUSION: Our study provided valuable insights into the critical role of PRGs in TME modulation, tumor stemness, and anticancer drug sensitivity across diverse cancers. Our findings illuminate the intricate relationship between pyroptosis and the TME, offering new perspectives for enhancing NSCLC treatment and prognosis.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Prognóstico , Piroptose/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Microambiente Tumoral
2.
Int J Biol Macromol ; 244: 125291, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37315670

RESUMO

Liver cancer can be primary (starting in the liver) or secondary (cancer that has spread from elsewhere to the liver, known as liver metastasis). Liver metastasis is more common than primary liver cancer. Despite great advances in molecular biology methods and treatments, liver cancer is still associated with a poor survival rate and a high death rate, and there is no cure. Many questions remain regarding the mechanisms of liver cancer occurrence and development as well as tumor reoccurrence after treatment. In this study, we assessed the protein structural features of 20 oncogenes and 20 anti-oncogenes via protein structure and dynamic analysis methods and 3D structural and systematic analyses of the structure-function relationships of proteins. Our aim was to provide new insights that may inform research on the development and treatment of liver cancer.


Assuntos
Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/patologia , Proteínas , Abdome/patologia
3.
Clin Respir J ; 17(5): 343-356, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37094822

RESUMO

Acquired digestive-respiratory tract fistulas occur with abnormal communication between the respiratory tract and digestive tract caused by a variety of benign or malignant diseases, leading to the alimentary canal contents in the respiratory tract. Although various departments have been actively exploring advanced fistula closure techniques, including surgical methods and multimodal therapy, some of which have gotten good clinical effects, there are few large-scale evidence-based medical data to guide clinical diagnosis and treatment. The guidelines update the etiology, classification, pathogenesis, diagnosis, and management of acquired digestive-respiratory tract fistulas. It has been proved that the implantation of the respiratory and digestive stent is the most important and best treatment for acquired digestive-respiratory tract fistulas. The guidelines conduct an in-depth review of the current evidence and introduce in detail the selection of stents, implantation methods, postoperative management and efficacy evaluation.


Assuntos
Fístula do Sistema Digestório , População do Leste Asiático , Fístula do Sistema Respiratório , Humanos , Consenso , Sistema Respiratório , Fístula do Sistema Respiratório/diagnóstico , Fístula do Sistema Respiratório/etiologia , Fístula do Sistema Respiratório/terapia , Stents/efeitos adversos , Resultado do Tratamento , Fístula do Sistema Digestório/diagnóstico , Fístula do Sistema Digestório/etiologia , Fístula do Sistema Digestório/terapia
4.
Cell Death Dis ; 13(6): 532, 2022 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-35668069

RESUMO

PTENα and PTENß (PTENα/ß), two long translational variants of phosphatase and tensin homolog on chromosome 10 (PTEN), exert distinct roles from canonical PTEN, including promoting carcinogenesis and accelerating immune-resistant cancer progression. However, their roles in carcinogenesis remain greatly unknown. Herein, we report that, after secreting into the extracellular space, PTENα/ß proteins are efficiently cleaved into a short N-terminal and a long C-terminal fragment by the proprotein convertase Furin at a polyarginine stretch in their N-terminal extensions. Although secreted PTENα/ß and their cleaved fragment cannot enter cells, treatment of the purified C-terminal fragment but not cleavage-resistant mutants of PTENα exerts a tumor-suppressive role in vivo. As a result, overexpression of cleavage-resistant PTENα mutants manifest a tumor-promoting role more profound than that of wild-type PTENα. In line with these, the C-terminal fragment is significantly downregulated in liver cancer tissues compared to paired normal tissues, which is consistent with the downregulated expression of Furin. Collectively, we show that extracellular PTENα/ß present opposite effects on carcinogenesis from intracellular PTENα/ß, and propose that the tumor-suppressive C-terminal fragment of PTENα/ß might be used as exogenous agent to treat cancer.


Assuntos
Furina , Neoplasias Hepáticas , Carcinogênese , Furina/genética , Humanos , Pró-Proteína Convertases
5.
Thorac Cancer ; 12(18): 2439-2448, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34337871

RESUMO

PURPOSE: The objective of our study was to investigate the epidemiologic characteristics and prognostic factors in patients with pulmonary acinar cell carcinoma (PACC). METHODS: PACC patients diagnosed between 1975 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The trend in PACC incidence was assessed using joinpoint regression software. Overall survival (OS) and disease-specific survival (DSS) were evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analysis was performed to identify the independent prognostic factors for OS and DSS. Nomograms to predict survival possibilities were constructed based on the identified independent prognostic factors. RESULTS: A total of 2918 patients were identified with PACC. The mean age was 65.2 ± 8.95 years with a female to male of 1.6:1. The incidence of PACC steadily increased by an annual percentage change (APC) of 3.2% (95% CI 2.1-4.4, p < 0.05). Multivariate Cox regression analysis revealed that age, gender, race, stage, grade, tumor size, number of positive lymph nodes, surgery, and chemotherapy were independent prognostic factors for survival. Nomograms specifically for PACC were constructed to predict 1- and 5-year OS and DSS possibility, respectively. The concordance index (C-index) and calibration plots showed the established nomograms had robust and accurate performance. CONCLUSION: PACC was rare but the incidence has been steadily increasing over the past four decades. Survival has improved in recent years. Surgery or chemotherapy could provide better OS and DSS. The established nomograms specifically for PACC were robust and accurate in predicting 1- and 5-year OS and DSS.


Assuntos
Carcinoma de Células Acinares/epidemiologia , Neoplasias Pulmonares/epidemiologia , Adulto , Idoso , Carcinoma de Células Acinares/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Programa de SEER , Taxa de Sobrevida , Estados Unidos/epidemiologia
6.
Soft Matter ; 17(8): 2191-2204, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33459746

RESUMO

An intrinsic self-healing polyurethane (PU) elastomer with excellent self-healing efficiency was prepared. The self-healing properties of this elastomer as well as the temperature dependence of self-healing can be tailored by regulating the molar ratio of hard to soft segments. The self-healing efficiency of 92.5% is the highest when the molar ratio of 4,4-methylenedicyclohexyl diisocyanate (HMDI) to polypropylene carbonate polyol (PPC) is 1.3 and the temperature is 25 °C. In situ temperature swing infrared spectra and low-field nuclear magnetic resonance reveal that the soft segment, PPC, endows PU with a dense dynamic hydrogen bond network, and the dissociation and reconstruction of the hydrogen bond network enable the PU to heal. To date, the exchange of hydrogen bonds has not been observed intuitively through experimental means. Therefore, the number, type, strength, lifetime, and the exchange of hydrogen bonds in the self-healing process at different temperatures were investigated by molecular dynamics (MD) simulation. The simulated results show that the type of hydrogen bond exchange between functional groups will be affected by temperature. The hydrogen bonds between urethane and urea groups play a leading role in the self-healing properties due to the high strength and a large number of hydrogen bonds at both 25 and 50 °C. The stronger strength, longer lifetime, and greater number of effective hydrogen bonds at 25 °C make the self-healing efficiency of PU higher than at 50 °C.

7.
Cell Metab ; 33(2): 270-282.e8, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33278339

RESUMO

Recent studies suggest that mitochondria can be transferred between cells to support the survival of metabolically compromised cells. However, whether intercellular mitochondria transfer occurs in white adipose tissue (WAT) or regulates metabolic homeostasis in vivo remains unknown. We found that macrophages acquire mitochondria from neighboring adipocytes in vivo and that this process defines a transcriptionally distinct macrophage subpopulation. A genome-wide CRISPR-Cas9 knockout screen revealed that mitochondria uptake depends on heparan sulfates (HS). High-fat diet (HFD)-induced obese mice exhibit lower HS levels on WAT macrophages and decreased intercellular mitochondria transfer from adipocytes to macrophages. Deletion of the HS biosynthetic gene Ext1 in myeloid cells decreases mitochondria uptake by WAT macrophages, increases WAT mass, lowers energy expenditure, and exacerbates HFD-induced obesity in vivo. Collectively, this study suggests that adipocytes and macrophages employ intercellular mitochondria transfer as a mechanism of immunometabolic crosstalk that regulates metabolic homeostasis and is impaired in obesity.


Assuntos
Tecido Adiposo Branco/metabolismo , Homeostase , Macrófagos/metabolismo , Mitocôndrias/metabolismo , Obesidade/metabolismo , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos
8.
Ther Adv Respir Dis ; 14: 1753466620976012, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33272105

RESUMO

BACKGROUND: Hemorrhage is a life-threatening complication during bronchoscopic intervention in patients with central airway obstruction (CAO) due to metastatic renal cell carcinoma (RCC). Whether pre-bronchoscopic bronchial arterial embolization (BAE) can reduce the risk of severe bleeding in CAO patients due to metastatic RCC remains unclear. METHODS: A total of 31 CAO patients due to metastatic RCC were included retrospectively and divided into a BAE group (receiving pre-bronchoscopic BAE) and non-BAE group in this study. Based on computed tomography (CT) and bronchoscopic findings, tumor debulking was used to reconstruct the airway during interventional bronchoscopy. The primary outcome was the incidence of severe bleeding during bronchoscopic procedures. Bleeding-related complications, Karnofsky performance score (KPS) and dyspnea score were also analyzed over a 1-month observation period. RESULTS: There were no significant differences between the two groups in baseline characteristics, including patients' features, tumor morphology under CT scannings, tumor site, and obstruction degree under bronchoscopic examination. Procedure-related bleeding occurred in all 31 patients. Pre-bronchoscopic BAE significantly reduced the incidence of moderate and major bleeding when compared with that in the non-BAE group. The incidence of poor visualization and hypoxia was also reduced significantly in the BAE group. There was no significant difference in KPS and dyspnea score between the BAE and non-BAE groups at 1 month follow up. CONCLUSION: Pre-bronchoscopic BAE might be a feasible option to reduce the risk of severe bleeding for CAO patients due to metastatic RCC during bronchoscopic intervention. Interventional bronchoscopy was a safe and effective procedure for CAO due to metastatic RCC.The reviews of this paper are available via the supplemental material section.


Assuntos
Obstrução das Vias Respiratórias/cirurgia , Neoplasias Brônquicas/cirurgia , Broncoscopia , Carcinoma de Células Renais/cirurgia , Embolização Terapêutica , Hemorragia/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Obstrução das Vias Respiratórias/etiologia , Artérias Brônquicas , Neoplasias Brônquicas/secundário , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/secundário , Feminino , Humanos , Complicações Intraoperatórias/prevenção & controle , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Ther Adv Respir Dis ; 13: 1753466619871523, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31476949

RESUMO

BACKGROUND: Thoracogastric-airway fistula (TGAF) post-thoracic surgery is a rare and challenging complication for esophagectomy. The aim of this study was to explore the effectiveness of airway stenting for TGAF patients and find related factors coupled with healing of fistula. METHODS: This is a retrospective study involving patients with TGAF who were treated with airway stentings. Based on different TGAF locations and sizes on chest computed tomography, covered metallic or silicon airway stents were implanted to cover orifices under interventional bronchoscopy. TGAF healing was defined as the primary outcome, and complete sealing of TGAF as the second outcome. The predictors for TGAF healing were analyzed in univariate and multivariate analysis. RESULTS: A total of 58 TGAF patients were included, of whom 7 received straight covered metallic stents, 5 straight silicon stents, 3 L-shaped covered metallic stents, 21 large Y-shaped covered metallic stents, 17 large Y-shaped silicon stents, and 5 with Y-shaped covered metallic stents. Healing was achieved in 20 (34.5%) patients, and complete sealing in 45 (77.6%) patients. There were no significant differences in healing rate and complete sealing rate between patients receiving metallic stents and those with silicon stents. In univariate analysis, lacking a previous history of radiotherapy or chemotherapy, nonmalignant fistulas, small fistulas, and shorter postesophagectomy duration were found associated with a higher rate of TGAF healing. Only shorter postesophagectomy duration was associated with TGAF healing in multivariate analysis. CONCLUSIONS: Both silicon and covered metallic airway stenting are effective methods to close TGAF. A shorter postesophagectomy period may predict better TGAF healing. The reviews of this paper are available via the supplemental material section.


Assuntos
Broncoscopia/instrumentação , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Fístula Gástrica/terapia , Fístula do Sistema Respiratório/terapia , Stents , Adulto , Idoso , Broncoscopia/efeitos adversos , Neoplasias Esofágicas/patologia , Feminino , Fístula Gástrica/diagnóstico por imagem , Fístula Gástrica/etiologia , Humanos , Masculino , Metais , Pessoa de Meia-Idade , Desenho de Prótese , Fístula do Sistema Respiratório/diagnóstico por imagem , Fístula do Sistema Respiratório/etiologia , Estudos Retrospectivos , Silicones , Fatores de Tempo , Resultado do Tratamento , Cicatrização
10.
Clinics ; 74: e700, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1001833

RESUMO

OBJECTIVES: This study was conducted to investigate the risk factors for pulmonary abscess-related empyema by investigating the clinical characteristics and chest computed tomography imaging features of patients with pulmonary abscesses. METHODS: We retrospectively analyzed the chest computed tomography findings and clinical features of 101 cases of pulmonary abscess, including 25 cases with empyema (the experimental group) and 76 cases with no empyema (the control group). The potential risk factors for pulmonary abscess-related empyema were compared between the groups by using univariate and multivariate logistic regression analyses. RESULTS: The incidence of pulmonary abscess-related empyema was 24.8% (25/101). Univariate analysis showed that male gender, diabetes, pleuritic symptoms, white blood cells >10×109/L, albumin level <25 g/L, and positive sputum cultures were potential clinical-related risk factors and that an abscess >5 cm in diameter and transpulmonary fissure abscesses were potential computed tomography imaging-related risk factors for pulmonary abscess-related empyema. Multivariate logistic regression analysis showed that transpulmonary fissure abscesses (odds ratio=9.102, p=0.003), diabetes (odds ratio=9.066, p=0.003), an abscess >5 cm in diameter (odds ratio=8.998, p=0.002), and pleuritic symptoms (odds ratio=5.395, p=0.015) were independent risk factors for pulmonary abscess-related empyema. CONCLUSIONS: Transpulmonary fissure abscesses, diabetes, giant pulmonary abscesses, and pleuritic symptoms increased the risk of empyema among patients with pulmonary abscesses.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Tomografia Computadorizada por Raios X/métodos , Empiema Pleural/diagnóstico por imagem , Abscesso Pulmonar/diagnóstico por imagem , Doenças Pleurais/complicações , Fatores Sexuais , Análise de Regressão , Fatores de Risco , Empiema Pleural/complicações , Empiema Pleural/sangue , Complicações do Diabetes/complicações , Albumina Sérica Humana/análise , Contagem de Leucócitos , Abscesso Pulmonar/complicações , Abscesso Pulmonar/sangue
11.
Thorac Cancer ; 9(11): 1544-1555, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30221470

RESUMO

Acquired respiratory-digestive tract fistulas occur with abnormal communication between the airways and digestive tract, causing the interflow of gas and liquid. Despite advances in surgical methods and the development of multimodal therapy in recent years, patients with acquired respiratory-digestive tract fistulas continue to exhibit unfavorable clinical outcomes. Therefore, in order to guide clinical practice in China, the Respiratory and Cancer Intervention Alliance of the Beijing Health Promotion Association organized a group of experienced experts in the field to develop this consensus document. Based on a study of clinical application and expert experience in the diagnosis and management of acquired respiratory-digestive tract fistulas at home and abroad, an Expert Consensus was developed. The panelists recruited comprised experts in pulmonology, oncology, thoracic surgery, interventional radiology, and gastroenterology. PubMed, Chinese Biology Abstract, Chinese Academic Journal, and Wanfang databases were used to identify relevant articles. The guidelines address etiology, classification, pathogenesis, diagnosis and management of acquired respiratory-digestive tract fistulas. The statements on treatment focus on the indications for different procedures, technical aspects, and preprocedural, post-procedural and complication management. The proposed guidelines for the diagnosis and management of acquired respiratory-digestive tract fistulas are the first to be published by Chinese experts. These guidelines provide an in-depth review of the current evidence and standard of diagnosis and management.


Assuntos
Consenso , Fístula/diagnóstico , Fístula/terapia , Trato Gastrointestinal/anormalidades , Sistema Respiratório/fisiopatologia , China , Feminino , Fístula/patologia , Humanos , Masculino
12.
Oncotarget ; 8(24): 38743-38754, 2017 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-28454121

RESUMO

Krüppel-like factor 17 (KLF17) has been reported to be involved in invasion and metastasis suppression in lung cancer, but the molecular mechanisms underlying the anti-invasion and anti-metastasis roles of KLF17 in lung cancer are not fully illustrated. Here, we showed that KLF17 inhibited the invasion of A549 and H322 cells; the anti-invasion effect of KLF17 was associated with the suppression of urokinase plasminogen activator (uPA/PLAU) expression. KLF17 can bind with the promoter of uPA and inhibit its expression. Enforced expression of uPA abrogated the anti-invasion effect of KLF17 in A549 and H322 cells. In addition, immunohistochemistry staining showed that the protein expression of KLF17 was negatively correlated with that of uPA in archived samples from patients with lymph node metastasis of lung adenocarcinoma (rho = -0.62, P = 0.01). The mutually exclusive expression of KLF17 with uPA could predict lymph node metastasis for lung adenocarcinoma (AUC = 0.758, P = 0.005). Enforced expression of KLF17 inhibited the expression of phosphorylated Src and phosphorylated p38/MAPK in A549 and H322 cells. The invasiveness of the cells were suppressed by treating with sb203580 (p38/MAPK inhibitor) or HY-13805 (PP2, Src inhibitor). furthermore, p38/MAPK inhibition could block the KLF17-induced reduction of p-p38/MAPK and uPA, and Src inhibition enhanced the KLF17-induced suppression of p-Src and uPA in A549 and H322 cells. In conclusion, our study indicated that KLF17 suppressed the uPA-mediated invasion of lung adenocarcinoma. The Src and p38/MAPK signaling pathways were suggested as mediators of KLF17-induced uPA inhibition, thus providing evidence that KLF17 might be a potential anti-invasion candidate for lung adenocarcinoma.


Assuntos
Adenocarcinoma/secundário , Movimento Celular , Neoplasias Pulmonares/patologia , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Metástase Linfática , Proteínas de Membrana/genética , Invasividade Neoplásica , Prognóstico , Proteínas Proto-Oncogênicas pp60(c-src)/genética , Taxa de Sobrevida , Fatores de Transcrição/genética , Células Tumorais Cultivadas , Proteínas Quinases p38 Ativadas por Mitógeno/genética
13.
Nat Cell Biol ; 17(12): 1546-55, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26551274

RESUMO

Endoplasmic reticulum (ER)-associated degradation (ERAD) represents a principle quality control mechanism to clear misfolded proteins in the ER; however, its physiological significance and the nature of endogenous ERAD substrates remain largely unexplored. Here we discover that IRE1α, the sensor of the unfolded protein response (UPR), is a bona fide substrate of the Sel1L-Hrd1 ERAD complex. ERAD-mediated IRE1α degradation occurs under basal conditions in a BiP-dependent manner, requires both the intramembrane hydrophilic residues of IRE1α and the lectin protein OS9, and is attenuated by ER stress. ERAD deficiency causes IRE1α protein stabilization, accumulation and mild activation both in vitro and in vivo. Although enterocyte-specific Sel1L-knockout mice (Sel1L(ΔIEC)) are viable and seem normal, they are highly susceptible to experimental colitis and inflammation-associated dysbiosis, in an IRE1α-dependent but CHOP-independent manner. Hence, Sel1L-Hrd1 ERAD serves a distinct, essential function in restraint of IRE1α signalling in vivo by managing its protein turnover.


Assuntos
Degradação Associada com o Retículo Endoplasmático/genética , Endorribonucleases/genética , Proteínas Serina-Treonina Quinases/genética , Resposta a Proteínas não Dobradas/genética , Animais , Sequência de Bases , Western Blotting , Células Cultivadas , Retículo Endoplasmático/metabolismo , Chaperona BiP do Retículo Endoplasmático , Endorribonucleases/metabolismo , Enterócitos/metabolismo , Feminino , Perfilação da Expressão Gênica , Células HEK293 , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Lectinas/genética , Lectinas/metabolismo , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas/genética , Proteínas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
14.
Am J Med Sci ; 350(5): 364-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26422803

RESUMO

BACKGROUND: Malignant tracheoesophageal fistula (MTEF) is a devastating complication of esophageal cancer, lung cancer or other carcinoma with a shorter life-span and poor life quality. The aim of this study was to assess the effect of airway stent insertion on MTEF patients. METHODS: A total of 63 MTEF patients were included, 12 patients with lung cancer and 46 patients with esophageal cancers. Eight zones were proposed to classify various fistula locations. Airway stents were selected based on the various zones and fistula size. RESULTS: Airway stents were successfully inserted in all patients, and both airway and esophageal stents in 8 patients. Most fistula were located in locations II (18/63, 28.6%), III (22/63, 34.9%), then VII (9/63, 14.3%). The stents included 10 (15.9%) I shaped, 8 (12.7%) L shaped and 45 (71.4%) Y shaped. Different stents were placed based on different locations and sizes of fistulas. Overall, mean survival time was 163 days (2-270 days). Most symptoms relieved after stent insertion. Mean Karnofsky score jumped from 43.0 ± 10.7 before stent placement to 66.7 ± 10.8 after stent insertion (P = 0.000). Complete closure was achieved in 45 patients (71.4%), and incomplete closure and leakage were found in 18 patients. CONCLUSIONS: Airway stent insertion provides an effective approach to improve symptoms and quality of life. The choice of stent based on different fistula location and size may be a reasonable way in clinical practice.


Assuntos
Broncoscopia/métodos , Neoplasias Esofágicas/complicações , Esôfago , Intubação , Neoplasias Pulmonares/complicações , Stents , Traqueia , Fístula Traqueoesofágica , Manuseio das Vias Aéreas/métodos , China/epidemiologia , Esôfago/patologia , Esôfago/cirurgia , Feminino , Humanos , Intubação/instrumentação , Intubação/métodos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Traqueia/patologia , Traqueia/cirurgia , Fístula Traqueoesofágica/diagnóstico , Fístula Traqueoesofágica/etiologia , Fístula Traqueoesofágica/mortalidade , Fístula Traqueoesofágica/cirurgia
15.
PLoS One ; 10(7): e0131894, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26154172

RESUMO

BACKGROUND: Insertion of T4 lysozyme (T4L) into the GPCR successfully enhanced GPCR protein stability and solubilization. However, the biological functions of the recombinant GPCR protein have not been analyzed. METHODS: We engineered the CCR5-T4L mutant and expressed and purified the soluble recombinant protein using an E.coli expression system. The antiviral effects of this recombinant protein in THP-1 cell lines, primary human macrophages, and PBMCs from different donors were investigated. We also explored the possible mechanisms underlying the observed antiviral effects. RESULTS: Our data showed the biphasic inhibitory and promotion effects of different concentrations of soluble recombinant CCR5-T4L protein on R5 tropic human immunodeficiency virus-1 (HIV-1) infection in THP-1 cell lines, human macrophages, and PBMCs from clinical isolates. We demonstrated that soluble recombinant CCR5-T4L acts as a HIV-1 co-receptor, interacts with wild type CCR5, down-regulates the surface CCR5 expression in human macrophages, and interacts with CCL5 to inhibit macrophage migration. Using binding assays, we further determined that recombinant CCR5-T4L and [125I]-CCL5 compete for the same binding site on wild type CCR5. CONCLUSIONS: Our results suggest that recombinant CCR5-T4L protein marginally promotes HIV-1 infection at low concentrations and markedly inhibits infection at higher concentrations. This recombinant protein may be helpful in the future development of anti-HIV-1 therapeutic agents.


Assuntos
Bacteriófago T4/enzimologia , Infecções por HIV/tratamento farmacológico , Muramidase/metabolismo , Receptores CCR5/metabolismo , Proteínas Recombinantes de Fusão/uso terapêutico , Células 3T3 , Animais , Antivirais/farmacologia , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Movimento Celular/efeitos dos fármacos , Quimiocina CCL5/farmacologia , Fatores Quimiotáticos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Escherichia coli/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Infecções por HIV/patologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/virologia , Camundongos , Monócitos/patologia , Ligação Proteica/efeitos dos fármacos , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/farmacologia , Solubilidade , Doadores de Tecidos , Tropismo Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
16.
Zhongguo Fei Ai Za Zhi ; 14(12): 933-7, 2011 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-22152693

RESUMO

BACKGROUND AND OBJECTIVE: The locations of mediastinal malignant tumor lesions are deep and occult, and are close to the pericardium, trachea, or major vessels. Therefore, the possibility of surgical resection is slim, and cryoablation and thermal ablation are restricted. In current study, image and life quality data were compared before and after 125I seeding therapy to investigate its safety and clinical effects. METHODS: From July 2010 to July 2011, a 43-patient follow-up of pathologically confirmed cancers, including 21 cases of primary mediastinal squamous lung cancer, 9 cases of primary esophagus cancer, and 13 cases of lymph node metastases were completed. Among these, 18 cases presented with tracheal stenosis >50%, 9 cases had esophageal obstruction, and 9 cases had superior vena cava reflux disorder. Each lesion was implanted with 10 to 60 pieces of 125I particles, with an average of 30.79±14.23. CT data at 2, 4, 6, and 12 months after therapy were obtained to evaluate the local lesion outcome. The quality of life of the patients as well as survival data was also recorded. RESULTS: The overall success rate of the operation was 100%. The longest time of follow-up was 12 months. At 6 months, 37 patients were alive, and the half-year survival rate was 85.0%. In terms of local lesions, 30 cases of PR and 7 cases of NC were found. The clinical effective rate was 81.08%, and the clinical beneficial rate was 100%. At 12 months after therapy, 31 patients were alive, and the one-year survival rate was 60.5%. In terms of local lesions, 16 cases of CR, 7 cases of PR, 2 cases of NC, and 6 cases of PD were found. The clinical effective rate was 74.19%, and the clinical beneficial rate was 80.65%. The KPS score increased after the treatment (P=0.000). Three cases of pneumothorax presented after treatment, and no severe complications, such as vessel, trachea, recurrent laryngeal nerve, or pericardiocentesis injuries, were found. CONCLUSIONS: Radiation seed implantation in mediastinal malignant tumors is a relatively safe technique with high success rate, considerable efficacy, and clear clinical value in advanced cancer treatment.


Assuntos
Radioisótopos do Iodo/uso terapêutico , Neoplasias Pulmonares/radioterapia , Metástase Linfática/radioterapia , Neoplasias do Mediastino/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Neoplasias do Mediastino/mortalidade , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
17.
Zhongguo Fei Ai Za Zhi ; 14(8): 679-84, 2011 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-21859550

RESUMO

BACKGROUND: Treating airway fistulas, including esophagorespiratory fistulas (ERFs), bronchopleural fistulas (BPFs), and tracheomediastinal fistulas (TMFs), is difficult. The aim of this study is to evaluate the safety and clinical efficacy of metallic covered Z-type stents (CZTS) for the treatment of airway fistulas through bronchoscopy or fluroscopy. METHODS: Thirty-eight patients with fistulas between the esophagus, mediastina, and airways (32 ERFs, 5 BPFs, and 1 TMF) were retrospectively reviewed after treatment with covered metallic esophageal and airway stents. The fistulas were caused by esophageal (n=26), bronchogenic (n=11), and thyroid (n=1) carcinomas. RESULTS: Forty-six fistulas were found in 38 patients. The fistula size ranged from 0.5 cm to 7.0 cm. Forty airway covered metal stents (24 Y-type, 8 L-type, and 8 I-type) and 24 esophageal metal stents were placed. Complete responses to the sealing effects of fistulas were noted in 4.3% of all the fistulas, 60.9% showed complete clinical responses, 23.9% showed partial responses, and 10.9% showed no response. An effectivity rate of 89.1% was observed, and the median survival duration of all patients was 5 months. CONCLUSIONS: The use of CZTS appears to be safe and feasible for the palliative treatment of ERFs, BPFs, and TMFs. Airway stent placement is recommended for patients with ERF. In the event that airway stents fail, esophageal stents should be given. Airway bifurcation stents were observed to be especially suitable for the sealing of fistulas near the trachea carina.


Assuntos
Broncoscopia/instrumentação , Fístula Esofágica/cirurgia , Fístula do Sistema Respiratório/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents
18.
Zhongguo Fei Ai Za Zhi ; 13(9): 898-902, 2010 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-20840820

RESUMO

BACKGROUND AND OBJECTIVE: It is a complex problem and difficult treatment for tracheobronchial stenoses/occlusions involving in carina. The aim of this study is to investigate the feasibility and efficiency of argon plasma coagulation (APC) and bifurcated covered Z-type stents (CZTS) placement for the treatment of tracheobronchus stenoses and esophagorespiratory fistula (ERF). METHODS: Thirty-two cases with airway disorders were retrospectively reviewed for the treatment of APC and CZTS placement. Under the bronchoscopic guidance, APC was first given in patients with airway stenoses, then CZTS was placed under the fluoroscopic and flexible bronchoscopic guidance either with airway stenoses or ERF. RESULTS: APC was first given in 19 patients with airway stenoses. Airway structures were significantly improved after APC procedure (57.4%-72.1% before APC vs 12.8%-25.8% after APC). Thirty-two CZTS were technically successfully placed in 30 out of 32 cases involving in carinal bifurcation. After APC and stent placement, short breath index was significantly reduced and karnofsky physical score (KPS) increased obviously. The endobronchial defects were successfully palliated with bifurcated CZTS placed under fluoroscopy and flexible bronchoscopy in 12 out of 13 patients with ERFs. There is no bleeding introprocedure. Mucous retention was very common in all types of the stents less than 2 weeks after stenting, which required debridement by bronchoscopy and could be prevented by normal saline solution nebulizations. Granuloma developed at the ends of stents after 1 month of stenting which all of them were treated successfully with APC and CO2 cryosurgery. CONCLUSIONS: Utilization of APC and retrieval bifurcated CZTS placement is a simple and safe protocol for the management of airway complex stenoses involving the tracheal carina and ERF.


Assuntos
Coagulação com Plasma de Argônio , Fístula Esofágica/terapia , Fístula do Sistema Respiratório/terapia , Stents , Estenose Traqueal/terapia , Idoso , Idoso de 80 Anos ou mais , Fístula Esofágica/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fístula do Sistema Respiratório/cirurgia , Estudos Retrospectivos , Estenose Traqueal/cirurgia
19.
Zhongguo Fei Ai Za Zhi ; 13(1): 60-3, 2010 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-20672706

RESUMO

BACKGROUND AND OBJECTIVE: TACE, Ar-He target cryosurgery and radioactive seeds implantation are the mainly micro-invasive methods in the treatment of lung cancer. This article summarizes the survival quality after treatment, the clinical efficiency and survival period, and analyzes the advantages and shortcomings of each methods so as to evaluate the clinical effect of non-small cell lung cancer with multiple minimally invasive treatment. METHODS: All the 139 cases were non-small cell lung cancer patients confirmed by pathology and with follow up from July 2006 to July 2009 retrospectively, and all of them lost operative chance by comprehensive evaluation. Different combination of multiple minimally invasive treatments were selected according to the blood supply, size and location of the lesion. Among the 139 cases, 102 cases of primary and 37 cases of metastasis to mediastinum, lung and chest wall, 71 cases of abundant blood supply used the combination of superselective target artery chemotherapy, Ar-He target cryoablation and radiochemotherapy with seeds implantation; 48 cases of poor blood supply use single Ar-He target cryoablation; 20 cases of poor blood supply use the combination of Ar-He target cryoablation and radiochemotheraoy with seeds implantation. And then the pre- and post-treatment KPS score, imaging data and the result of follow up were analyzed. RESULTS: The KPS score increased 20.01 meanly after the treatment. Follow up 3 years, 44 cases of CR, 87 cases of PR, 3 cases of NC and 5 cases of PD, and the efficiencywas 94.2%. Ninety-nine cases of 1 year survival (71.2%), 43 cases of 2 years survival (30.2%), 4 cases with over 3 years survival and the median survival was 19 months. Average survival was (16 +/- 1.5) months. There was no severe complications, such as spinal cord injury, vessel and pericardial aspiration. CONCLUSION: Minimally invasive technique is a highly successful, micro-invasive and effective method with mild complications. To non-small cell lung cancer, we can improve the middle and long term clinical effect by using the different combination of multiple minimally invasive treatments according to the patient's condition.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Criocirurgia/métodos , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
20.
Zhongguo Fei Ai Za Zhi ; 13(5): 540-3, 2010 May.
Artigo em Chinês | MEDLINE | ID: mdl-20677656

RESUMO

BACKGROUND AND OBJECTIVE: Transcatheter arterial chemotherapy and embolization is the main method in the treatment of lung cancer, but most of the reports do not study individually to small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), hypovascular and hypervascular lung cancer. The pre-embolization perfusion of hemotherapeutics is still being used routinely and seldom report to iodized oil embolization. The article summarized the quality of life after the treatment, clinical efficiency, survival time and complications to evaluate the clinical effect of primary hypervascular NSCLC treated with embolization of emulsion of chemotherapeutics and iodized oil. METHODS: The study totally analyzed 41 cases which confirmed by pathology and follow up study from January, 2008 to January 2009. The CT scan with IV contrast demonstrates over moderate enhanced lesion which indicate hypervascular. Within the 41 cases, 23 cases of central, 18 cases of peripheral. Suqamous carcinoma 21 cases, adenocarcinoma 15 cases and squamoadenocarcinoma 5 cases. Stage IIIb 34 cases, stage IV 7 cases. Superselective incubation with microcatheter under DSA, to embolize the capillary bed with liquefied iodized oil and the emulsion of pharmorubicin, to embolize the supply artery of the tumor with gelatin foam microparticle. The liquefied iodized oil 5 mL-10 mL, pharmorubicin 10 mg-30 mg. The longest follow up is 12 months and to compare with the references of 2007-2009. RESULTS: The KPS is widely acclaimed after the treatment (P < 0.05), no complete response (CR), 31 cases of partial response (PR), 7 cases of no change (NC) and 3 cases of progressive disease (PD), the total efficiency (CR+PR) is 75.6%. The clinical efficiency (CR+PR+NC) is 92.68%. 33 cases of total survival tome over 12 months (80.48%), IIIb stage 29/34 (85.29%), IV stage 4/7 (57.14%). 1 case with severe complication-spinal injury. CONCLUSION: To treat primary hypervascular NSCLC with simple embolization of emulsion of chemotherapeutics and iodized oil is very useful and can avoid the side effect of chemotherapeutics. The key point to avoid spinal injury and other severe complications is to distinguish the spinal aretery and intratumor AV fistula by using superselective incubation with microcatheter under DSA.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimioembolização Terapêutica , Óleo Iodado/administração & dosagem , Neoplasias Pulmonares/terapia , Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Emulsões , Feminino , Humanos , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade
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