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The relationship between Toll-like receptor 9 (TLR-9) signaling and its involvement with Epstein-Barr virus (EBV) in gastric cancer (GC) is complex and currently under study. This research intended to understand TLR-9's role in certain T and B lymphocytes and the serum levels of TLR-9 in GC patients versus healthy subjects. The team explored links between these immune markers and various GC traits, such as histological grade, tumor progression stages, cancer types, and survival rates. Additionally, the research sought to find if EBV genetic material influences these immune reactions. Using flow cytometry, TLR-9 levels in different immune cells were analyzed. At the same time, the amount of TLR-9 in the serum was determined. The results showed GC patients had varied TLR-9 levels compared to healthy subjects, with specific cells showing noticeable changes. When grouped by GC attributes, key relationships emerged between TLR-9 amounts, the histological grade, progression stages, and cancer types. A notable finding was the connection between TLR-9 levels and EBV genetic presence, suggesting possible interactions between TLR-9 responses and EBV-related GC processes. Survival data also hinted at TLR-9's potential as a predictor linked to clinical traits. Overall, this research emphasizes TLR-9's complex role in GC's immune responses, pinpointing its interactions with particular cells, clinical features, and EBV. The study unveils a complex web affecting GC and paves the way for new treatment avenues targeting TLR-9 pathways.
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Gastric cancer is one of the five most common types of cancer worldwide. Due to the heterogeneous course and the involvement of many risk factors, its treatment and diagnosis is an important challenge for modern medicine. Recent studies have emphasized the i role of Toll-like receptors (TLRs) expressed on selected cells of the immune system in the pathogenesis of gastric cancer. The aim of this study was to determine the prevalence of TLR2 on T lymphocytes, B lymphocytes, monocytes, and dendritic cells in patients diagnosed with gastric cancer, with particular emphasis on the stage of the disease. Based on the obtained results, we have shown that patients with gastric cancer are characterized by a higher percentage of all tested populations of peripheral blood immune cells expressing TLR2 in relation to patients from the control group. Moreover, a detailed analysis of the collected results showed a significant link between TLR2 and the stage of the disease.
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Neoplasias Gástricas , Receptor 2 Toll-Like , Humanos , Receptor 2 Toll-Like/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Receptor 4 Toll-Like , Receptores Toll-Like , Biomarcadores , Receptor Toll-Like 9RESUMO
Gastric cancer remains one of the most commonly diagnosed cancers in the world, with a relatively high mortality rate. Due to the heterogeneous course of the disease, its diagnosis and treatment are limited and difficult, and it is associated with a reduced prognosis for patients. That is why it is so important to understand the mechanisms underlying the development and progression of this cancer, with particular emphasis on the role of risk factors. According to the literature data, risk factors include: changes in the composition of the stomach and intestinal microbiota (microbiological dysbiosis and the participation of Helicobacter pylori), improper diet, environmental and genetic factors, and disorders of the body's immune homeostasis. Therefore, the aim of this review is to systematize the knowledge on the influence of human microbiota dysbiosis on the development and progression of gastric cancer, with particular emphasis on the role of the immune system in this process.
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OBJECTIVE: The aim was to describe initial outcomes of physician modified stent grafts using antegrade laser fenestrations and image fusion guidance (LEVAR) and company manufactured custom made (CM) stent grafts for the treatment of complex abdominal aortic aneurysms (CAAAs), thoraco-abdominal aortic aneurysms (TAAAs) and type I endoleaks (T1ELs). METHODS: This was a retrospective single centre study. All LEVAR and Zenith (Cook) CM stent graft procedures between 1 January 2012 and 31 December 2018 were reviewed. Endpoints included intra-operative adverse events (IOAEs), in hospital mortality, re-interventions, target vessel patency, and 12 month outcomes (overall survival, freedom from re-intervention, target vessel patency). Outcomes at 12 months were estimated using the Kaplan-Meier method. RESULTS: A hundred patients were identified and included in the study. All patients were deemed unfit for open repair. The cohort included 22 LEVAR and 78 CM stent grafts. LEVAR cases included painful aneurysms (n = 5), > 65 mm aneurysms (n = 10), anatomical constrains and/or presence of previous renal stents (n = 7) or cases declined by the manufacturer planning centre (n = 2). IOAEs were recorded in 41% of cases (n = 9) in the LEVAR group vs. 10% (n = 8, p = .002) in the CM group. The in hospital mortality rate in the LEVAR group was 9% (n = 2) vs. 4% (n = 3, p = .30) in the CM group. The median follow up duration was 22 months (7 - 38) in the LEVAR group and 28 months (11 - 78) in the CM group. The estimate of overall survival at one year was 91% in both groups. The freedom from re-intervention rate at one year was 58% in the LEVAR group vs. 87% in the CM group. The target vessel patency rates at one year were 95% in both groups. CONCLUSION: In high risk patients deemed unfit for open repair, LEVAR may provide satisfactory 12 month overall survival and target vessel patency rates, though reported IOAE, mortality, and re-interventions rates were high thus requiring close and extensive follow up.
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Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Prótese Vascular , Endoleak/cirurgia , Procedimentos Endovasculares/instrumentação , Idoso , Idoso de 80 Anos ou mais , Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/efeitos adversos , Tomografia Computadorizada de Feixe Cônico , Endoleak/etiologia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Feminino , Fluoroscopia , Mortalidade Hospitalar , Humanos , Complicações Intraoperatórias/etiologia , Terapia a Laser , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Complicações Pós-Operatórias/etiologia , Reoperação , Estudos Retrospectivos , Stents/efeitos adversos , Cirurgia Assistida por Computador , Taxa de Sobrevida , Grau de Desobstrução VascularRESUMO
Mutations in IFN and MHC signaling genes endow immunotherapy resistance. Patients with colorectal cancer infrequently exhibit IFN and MHC signaling gene mutations and are generally resistant to immunotherapy. In exploring the integrity of IFN and MHC signaling in colorectal cancer, we found that optineurin was a shared node between the two pathways and predicted colorectal cancer patient outcome. Loss of optineurin occurs in early-stage human colorectal cancer. Immunologically, optineurin deficiency was shown to attenuate IFNGR1 and MHC-I expression, impair T-cell immunity, and diminish immunotherapy efficacy in murine cancer models and patients with cancer. Mechanistically, we observed that IFNGR1 was S-palmitoylated on Cys122, and AP3D1 bound with and sorted palmitoylated IFNGR1 to lysosome for degradation. Unexpectedly, optineurin interacted with AP3D1 to prevent palmitoylated IFNGR1 lysosomal sorting and degradation, thereby maintaining IFNγ and MHC-I signaling integrity. Furthermore, pharmacologically targeting IFNGR1 palmitoylation stabilized IFNGR1, augmented tumor immunity, and sensitized checkpoint therapy. Thus, loss of optineurin drives immune evasion and intrinsic immunotherapy resistance in colorectal cancer. SIGNIFICANCE: Loss of optineurin impairs the integrity of both IFNγ and MHC-I signaling pathways via palmitoylation-dependent IFNGR1 lysosomal sorting and degradation, thereby driving immune evasion and intrinsic immunotherapy resistance in colorectal cancer. Our work suggests that pharmacologically targeting IFNGR1 palmitoylation can stabilize IFNGR1, enhance T-cell immunity, and sensitize checkpoint therapy in colorectal cancer.See related commentary by Salvagno and Cubillos-Ruiz, p. 1623.This article is highlighted in the In This Issue feature, p. 1601.
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Proteínas de Ciclo Celular/metabolismo , Neoplasias Colorretais/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Receptores de Interferon/metabolismo , Animais , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Feminino , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Interferon gama/metabolismo , Lipoilação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Transporte Proteico , Organismos Livres de Patógenos Específicos , Receptor de Interferon gamaRESUMO
BACKGROUND: We report a case of juxtarenal abdominal aortic aneurysm-anatomically unsuitable for conventional endovascular repair because of narrow distal aorta-successfully treated by endovascular repair facilitated by in situ laser fenestration. METHODS AND RESULTS: An aortic stent graft was inserted to exclude a juxtarenal aneurysm: under image fusion guidance, antegrade in situ laser fenestration allowed to perfuse superior mesenteric artery and both renal arteries. After complementary insertion of an extended aortouni-iliac stent graft, retrograde in situ laser fenestration was performed to perfuse the contralateral left iliac artery, in order to overcome a narrow distal aorta. Postoperative course was uneventful. Six month's CT showed an excluded aneurysm, patency of the inserted stents and the absence of endoleak. CONCLUSIONS: In situ laser fenestration seems to be an effective solution for endovascular therapy of complex juxtarenal aneurysms. In this case of narrow distal aorta it was a suitable alternative to overcome endovascular aneurysm repair anatomical restrictions and to prevent other additional open surgical interventions.
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Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Stents , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/fisiopatologia , Humanos , Masculino , Desenho de Prótese , Fluxo Sanguíneo Regional , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
OBJECTIVE: To evaluate feasibility, efficacy and overall functional success of image fusion guidance during laser-assisted in situ fenestration of aortic stent graft (LISFAS) for endovascular repair of complex aortic aneurysm (complex-EVAR) in a prospective study. METHODS: Between September 2016 and July 2018, 20 patients were included and treated with LISFAS for complex-EVAR. Aortic aneurysms were either para-renal (n = 15) or thoraco-abdominal (n = 5) with 57 mm [first quartile: 54; third quartile: 68] median aneurysm diameter in 69 years [68;78] patients. All interventions were performed using the same angiographic system and 3D image fusion software for overlying pre-intervention CTA on per-intervention 2D fluoroscopy with cone-beam CT images to display target vessels ostia. RESULTS: LISFAS for complex-EVAR with image fusion was performed in all patients, and no endovascular intervention required conversion to an open aortic repair. LISFAS of all target vessels was feasible in 18 patients (90%); 48 fenestrations out of 50 were performed successfully. Two fenestrations failed for renal arteries in two patients. Median ischemic times were as follows: 34 min [25;43] for superior mesenteric artery; 69 min [56;83] for left renal artery; 73 min [36;102] for right renal artery; and 93 min [89;96] for the celiac trunk. Median intervention and fluoroscopy times, iodinated contrast volume and X-ray exposure were 180 min [150;180], 74 min [64;87], 80 mL [59;113] and 338 Gy.cm2 [259;495], respectively. Efficacy was found in 17 patients (85%) on one-week follow-up CTA: Two patients had type 1 and 3 endoleaks, respectively, that were successfully embolized. Overall functional success was 90%. Median hospitalization stay was 9 days [8, 17]. The 30-day safety analysis was 90% (n = 2 deaths) owing to an undetermined cause and to bowel ischemia after low flow in intensive care unit. CONCLUSIONS: LISFAS using image fusion was feasible, efficient and overall functionally successful for complex-EVAR in this preliminary study.
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Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/cirurgia , Implante de Prótese Vascular/métodos , Angiografia por Tomografia Computadorizada/métodos , Procedimentos Endovasculares/métodos , Stents , Idoso , Tomografia Computadorizada de Feixe Cônico/métodos , Meios de Contraste , Estudos de Viabilidade , Feminino , Fluoroscopia/métodos , Humanos , Imageamento Tridimensional/métodos , Masculino , Estudos Prospectivos , Intensificação de Imagem Radiográfica/métodos , Resultado do TratamentoRESUMO
INTRODUCTION: Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) function as an immune checkpoint pathway that can be exploited by tumor cells to evade immuno-surveillance. The precise role of PD-1/PD-L1 inhibition of the immune response in GC is unknown. The study investigated PD-1 and PD-L1 expression on peripheral T-cells and its potential association with clinicopathological features in gastric cancer (GC) patients. MATERIAL AND METHODS: PD-1/PD-L1 expression on CD4(+) and CD8(+) T-cells from peripheral blood of 40 patients primarily diagnosed with advanced GC was evaluated by multicolor flow cytometry. RESULTS: The frequency of CD4(+)PD-1(+) and CD8(+)PD-1(+) cells in GC patients was higher than in the control group (p < 0.0001 and p < 0.01, respectively). Expression of PD-1 on CD8(+) cells in GC was higher than in the control group (p < 0.0001). The frequency of CD4(+)PD-L1(+) and CD8(+)PD-L1(+) cells was higher than in the control group (p < 0.0001). Expression of PD-L1 on CD4(+) and CD8(+) cells in GC was higher than in the control group (p < 0.0001). A higher frequency of CD4(+)PD-1(+) cells was found in diffuse-type compared to intestinal tumors (p < 0.029). A higher frequency of CD8(+)PD-1(+) cells was found in patients with poorly differentiated compared to well/moderately differentiated tumors (p < 0.019). CONCLUSIONS: Downregulation of peripheral blood CD4(+) and CD8(+) lymphocytes can be associated with PD-1/PD-L1 expression. This can lead to attenuation of the general immune response in GC.
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INTRODUCTION: Gastric cancer (GC) is one of the leading causes of cancer death worldwide. The membrane glycoprotein CD200, widely expressed on multiple cells/tissues, uses a structurally similar receptor (CD200R), delivering immunoregulatory signals. There is evidence that CD200/CD200R signaling suppresses anti-tumor responses in different types of malignancies. Little is known about the CD200/CD200R pathway in GC. The aim of the study was to evaluate the frequencies of CD200+ and CD200R+ lymphocytes in patients with GC. MATERIAL AND METHODS: Forty patients primarily diagnosed with GC and 20 healthy volunteers (control group) were enrolled. The viable peripheral blood lymphocytes underwent labeling with fluorochrome-conjugated monoclonal antibodies and were analyzed using a flow cytometer. RESULTS: In the GC group, the percentages of T CD3+, CD3+/CD4+, and CD3+/CD8+ cells expressing CD200 antigen were higher than in the control group (p < 0.00013, p < 0.0004, and p < 0.0006, respectively). In the GC group, the frequencies of T CD3+, CD3+/CD4+ and CD3+/CD8+ cells expressing CD200R were lower than in the control group (p < 0.0009, p < 0.004, and p < 0.002, respectively). The percentage of B CD19+/CD200+ lymphocytes was higher in GC patients than in the control group (p < 0.00005). Lower frequency of B CD19+/CD200R+ cells was observed in GC patients compared to the control group (p < 0.0001). No differences in the frequencies of CD200+ and CD200R+ lymphocytes were found in relation to either UICC stage or histological grading of the tumors. CONCLUSIONS: For GC pathogenesis, deregulation of the CD200/CD200R axis is important. High percentages of lymphocytes with CD200 expression may contribute to the continuous T cell activation and development of chronic inflammation and influence gastric carcinogenesis.
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The photocatalytically driven partial oxidation of a mustard gas simulant, 2-chloroethyl ethyl sulfide (CEES), was studied using the perylene-based metal-organic framework (MOF) UMCM-313 and compared to the activities of the Zr-based MOFs: PCN-222/MOF-545 and NU-1000. The rates of CEES oxidation positively correlated with the singlet oxygen quantum yield of the MOF linkers, porphyrin (PCN-222/MOF-545) < pyrene (NU-1000) < perylene (UMCM-313). Subsequently, thin films of UMCM-313 and NU-1000 were solvothermally grown on a conductive glass substrate to minimize catalyst loading and prevent light scattering by suspended MOF particles. Using a conductive glass support, the initial turnover frequencies of the MOFs in the photocatalytic reaction improved by 10-fold.
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Abdominal aortic aneurysms (AAA), also called "silent killer" as they grow without symptoms until the final rupture, are the 3rd cause of cardiovascular deaths, after myocardial infarction and stroke. Surgery is the only efficient way of preventing aortic rupture. The initial technique, described by Charles Dubost in 1952 has evolved and results and provides fair long-term results: open repair (OR) is performed under general anesthesia, via a transperitoneal or a retroperitoneal approach. Laparoscopic repair aims to reduce the consequences of surgery, but its role is still debated due to limited experience and to variable results. Since initial reports by Volodos, and Parodi of endovascular aortic repair (EVAR) in 1993, there have been continuous technological improvements, initiated by Claude Mialhe's "modular" and "bifurcated" concepts. More recently, novel techniques and new devices have contributed to the widening of EVAR indications. In this article, we describe 20 years of our EVAR experience.
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Aneurisma da Aorta Abdominal/cirurgia , Prótese Vascular , Procedimentos Endovasculares , Aneurisma da Aorta Abdominal/epidemiologia , Ruptura Aórtica/cirurgia , Prótese Vascular/efeitos adversos , Prótese Vascular/tendências , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/tendências , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Resultado do TratamentoRESUMO
Colorectal cancer includes an invasive stem-like/mesenchymal subtype, but its genetic drivers, functional, and clinical relevance are uncharacterized. Here we report the definition of an altered miRNA signature defining this subtype that includes a major genomic loss of miR-508. Mechanistic investigations showed that this miRNA affected the expression of cadherin CDH1 and the transcription factors ZEB1, SALL4, and BMI1. Loss of miR-508 in colorectal cancer was associated with upregulation of the novel hypoxia-induced long noncoding RNA AK000053. Ectopic expression of miR-508 in colorectal cancer cells blunted epithelial-to-mesenchymal transition (EMT), stemness, migration, and invasive capacity in vitro and in vivo In clinical colorectal cancer specimens, expression of miR-508 negatively correlated with stemness and EMT-associated gene expression and positively correlated with patient survival. Overall, our results showed that miR-508 is a key functional determinant of the stem-like/mesenchymal colorectal cancer subtype and a candidate therapeutic target for its treatment.Significance: These results define a key functional determinant of a stem-like/mesenchymal subtype of colorectal cancers and a candidate therapeutic target for its treatment. Cancer Res; 78(7); 1751-65. ©2018 AACR.
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Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Células-Tronco Mesenquimais/citologia , MicroRNAs/genética , Animais , Antígenos CD/biossíntese , Células CACO-2 , Caderinas/biossíntese , Linhagem Celular Tumoral , Movimento Celular/genética , Células HCT116 , Células HT29 , Humanos , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Invasividade Neoplásica/genética , Transplante de Neoplasias , Complexo Repressor Polycomb 1/biossíntese , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , Fatores de Transcrição/biossíntese , Transplante Heterólogo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/biossínteseRESUMO
BACKGROUND: The objective of the study was to evaluate the feasibility and early outcomes of complex aortic aneurysm repair in high-risk patients with hostile anatomies using both parallel stents and physician-modified stent graft (PMSG) techniques to address the renovisceral arteries. METHODS: Consecutive patients with complex suprarenal (SRA) and thoracoabdominal aortic aneurysms (TAAAs) undergoing endovascular repair using combined parallel stents technique and PMSG between September 2013 and November 2015 were evaluated. All patients required prompt aneurysm treatment. Fenestrations to preserve branch vessels were created in thoracic stent grafts. Depending on the anatomy, chimney or snorkel stents were deployed in renal or visceral arteries as complementary technique to overcome severe angulations or preexisting suprarenal stent. Preoperative, intraoperative, and postoperative data were recorded by means of a prospectively maintained database. RESULTS: Six high-risk patients with TAAA (type I: n = 2, type III: n = 1) and SRA (n = 3) underwent endovascular repair using both parallel stents technique and PMSG. Indications were painful aneurysms (n = 1) and >70-mm rapidly enlarging aneurysms (n = 5). Ten thoracic components were used, of which 6 were modified intraoperatively. Twenty-one renovisceral arteries were revascularized, using dedicated fenestrations (n = 10, 47.7%), chimney (n = 7, 33.3%), and snorkel stents (n = 4, 19%). The mean operative time was 326 ± 82 min including the device modification time. The mean time for graft modification was 90 ± 15 min. In 1 patient, a rescue chimney stent intended to the superior mesenteric artery was deployed because of failed cannulation through the dedicated fenestration. Technical success rate was 83.3%. One patient died during the early postoperative course from severe stroke. Among surviving patients, 3 required early reinterventions for iliac occluder-related type II endoleak (n = 1), type Ia endoleak (n = 1), and gastroduodenal artery embolization (n = 1). The mean follow-up was 14.2 ± 4.8 months. One early gutter-related type I endoleak resolved during follow-up. No other complications occurred, and all target vessels remained patent. CONCLUSIONS: PMSG combined with parallel stent provided acceptable short-term results in specific presentation of SRA and TAAA with hostile anatomies in selected high-risk patients with contraindication for standard fenestrated/branched grafts. More reliable outcomes require larger population and follow-up.
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Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Papel do Médico , Desenho de Prótese , Stents , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/mortalidade , Aortografia/métodos , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Angiografia por Tomografia Computadorizada , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Estudos de Viabilidade , Feminino , Humanos , Masculino , Duração da Cirurgia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Retratamento , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
The expression and biological role of IL33 in colon cancer is poorly understood. In this study, we show that IL33 is expressed by vascular endothelial cells and tumor cells in the human colon cancer microenvironment. Administration of human IL33 and overexpression of murine IL33 enhanced human and murine colon cancer cell growth in vivo, respectively. IL33 stimulated cell sphere formation and prevented chemotherapy-induced tumor apoptosis. Mechanistically, IL33 activated core stem cell genes NANOG, NOTCH3, and OCT3/4 via the ST2 signaling pathway, and induced phosphorylation of c-Jun N terminal kinase (JNK) activation and enhanced binding of c-Jun to the promoters of the core stem cell genes. Moreover, IL33 recruited macrophages into the cancer microenvironment and stimulated them to produce prostaglandin E2, which supported colon cancer stemness and tumor growth. Clinically, tumor IL33 expression associated with poor survival in patients with metastatic colon cancer. Thus, IL33 dually targets tumor cells and macrophages and endows stem-like qualities to colon cancer cells to promote carcinogenesis. Collectively, our work reveals an immune-associated mechanism that extrinsically confers cancer cell stemness properties. Targeting the IL33 signaling pathway may offer an opportunity to treat patients with metastatic cancer. Cancer Res; 77(10); 2735-45. ©2017 AACR.
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Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Interleucina-33/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Macrófagos/metabolismo , Células-Tronco Neoplásicas/metabolismo , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Quimiotaxia de Leucócito/genética , Quimiotaxia de Leucócito/imunologia , Neoplasias do Colo/imunologia , Neoplasias do Colo/mortalidade , Modelos Animais de Doenças , Expressão Gênica , Xenoenxertos , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Macrófagos/imunologia , Masculino , Camundongos , Prognóstico , Proteínas Proto-Oncogênicas c-jun/genética , Proteínas Proto-Oncogênicas c-jun/metabolismo , Células Tumorais CultivadasRESUMO
BACKGROUND: Ruptured descending thoracic aortic aneurysm (rDAA) is a rare but devastating condition. Open aortic surgery which uses cardiopulmonary bypass is associated with a high mortality. Thoracic endovascular aortic repair (TEVAR) is a less-invasive approach for which it remains unclear whether outcomes are superior or equivalent to open aortic surgery. In this study, we report our early and midterm outcomes with TEVAR for rDAA. METHODS: This is an observational, retrospective, single-center study which included patients with rDAA and treated by TEVAR. The main objective was the 30-day in-hospital mortality. Secondary end points were 30-day in-hospital morbidity, 2-year mortality, and technical problems encountered during procedures. RESULTS: Twenty-five patients were included: 14 men and 11 women with a median age of 76 years (69-82 years). Thirty-day in-hospital mortality rate was 36% (95% confidence interval [CI], 20.6-57.9; n = 9), and the 2-year mortality rate was 44% (95% CI, 27.94-66.72; n = 11). Fifteen patients (60%) presented at least 1 major complication, and 8 of those patients had a second surgery because of it. There were 9 technical problems encountered that required additional open procedures to successfully deploy the aortic stent graft: lack of vascular access in 2 cases (8%), short proximal neck in 3 cases (12%), and short distal neck in 4 cases (16%). CONCLUSIONS: Mortality and morbidity remain high in patients treated for rDAA by TEVAR. Nonetheless, TEVAR remains an interesting alternative to open aortic surgery especially for older patients with a poor general health and functional status.
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Aneurisma da Aorta Torácica/cirurgia , Ruptura Aórtica/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/mortalidade , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/mortalidade , Aortografia/métodos , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Angiografia por Tomografia Computadorizada , Emergências , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , França , Mortalidade Hospitalar , Humanos , Masculino , Seleção de Pacientes , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the role of salivary stimulation and esophageal secretion of protective factors in prevention of adenocarcinoma sequelae in gastroesophageal reflux disease; the pediatric conditions associated with esophageal cancer; the relationship of achalasia and pseudoachalasia with esophageal cancer; the potential for malignant transformation in eosinophilic esophagitis and overlap syndromes; the role of lymphocytic esophagitis as an overlapping phenotype; the role of Barrett's esophagus as a premalignant condition; the indications and type of treatment of premalignant conditions of the esophagus; and the decision for use of endoscopical procedures in premalignant conditions of the esophagus.
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Neoplasias Esofágicas/diagnóstico , Esôfago/patologia , Lesões Pré-Cancerosas/diagnóstico , Animais , Esôfago de Barrett/complicações , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/terapia , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/terapia , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/terapia , Humanos , Paris , Lesões Pré-Cancerosas/complicações , Lesões Pré-Cancerosas/terapia , Plexo Submucoso/patologiaRESUMO
Little is known about how the immune system impacts human colorectal cancer invasiveness and stemness. Here we detected interleukin-22 (IL-22) in patient colorectal cancer tissues that was produced predominantly by CD4(+) T cells. In a mouse model, migration of these cells into the colon cancer microenvironment required the chemokine receptor CCR6 and its ligand CCL20. IL-22 acted on cancer cells to promote activation of the transcription factor STAT3 and expression of the histone 3 lysine 79 (H3K79) methytransferase DOT1L. The DOT1L complex induced the core stem cell genes NANOG, SOX2, and Pou5F1, resulting in increased cancer stemness and tumorigenic potential. Furthermore, high DOT1L expression and H3K79me2 in colorectal cancer tissues was a predictor of poor patient survival. Thus, IL-22(+) cells promote colon cancer stemness via regulation of stemness genes that negatively affects patient outcome. Efforts to target this network might be a strategy in treating colorectal cancer patients.
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Linfócitos T CD4-Positivos/imunologia , Neoplasias Colorretais/imunologia , Interleucinas/imunologia , Metiltransferases/imunologia , Células-Tronco Neoplásicas/imunologia , Fator de Transcrição STAT3/imunologia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Quimiocina CCL20/imunologia , Quimiocina CCL20/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Ativação Enzimática/imunologia , Células HT29 , Histona-Lisina N-Metiltransferase , Proteínas de Homeodomínio/imunologia , Proteínas de Homeodomínio/metabolismo , Humanos , Metiltransferases/metabolismo , Camundongos , Proteína Homeobox Nanog , Transplante de Neoplasias , Células-Tronco Neoplásicas/patologia , Fator 3 de Transcrição de Octâmero/imunologia , Fator 3 de Transcrição de Octâmero/metabolismo , Receptores CCR6/imunologia , Receptores CCR6/metabolismo , Fatores de Transcrição SOXB1/imunologia , Fatores de Transcrição SOXB1/metabolismo , Fator de Transcrição STAT3/metabolismo , Interleucina 22RESUMO
OBJECTIVE: Fenestrated and branched endovascular devices are increasingly used for complex aortic diseases, and despite the challenging nature of these procedures, early experiences from pioneering centers have been encouraging. The objectives of this retrospective study were to report our experience of intraoperative adverse events (IOAEs) during fenestrated and branched stent grafting and to analyze the impact on clinical outcomes. METHODS: Consecutive patients treated with fenestrated and branched stent grafting in a tertiary vascular center between February 2006 and October 2013 were evaluated. A prospectively maintained computerized database was scrutinized and updated retrospectively. Intraoperative angiograms were reviewed to identify IOAEs, and adverse events were categorized into three types: target vessel cannulation, positioning of graft components, and intraoperative access. Clinical consequences of IOAEs were analyzed to ascertain whether they were responsible for death or moderate to severe postoperative complications. RESULTS: During the study period, 113 consecutive elective patients underwent fenestrated or branched stent grafting. Indications for treatment were asymptomatic complex abdominal aortic aneurysms (CAAAs, n = 89) and thoracoabdominal aortic aneurysms (TAAAs, n = 24). Stent grafts included fenestrated (n = 79) and branched (n = 17) Cook stent grafts (Cook Medical, Bloomington, Ind), Ventana (Endologix, Irvine, Calif) stent grafts (n = 9), and fenestrated Anaconda (Vascutek Terumo, Scotland, UK) stent grafts (n = 8). In-hospital mortality rates for the CAAA and TAAA groups were 6.7% (6 of 89) and 12.5% (3 of 24), respectively. Twenty-eight moderate to severe complications occurred in 21 patients (18.6%). Spinal cord ischemia was recorded in six patients, three of which resolved completely. A total of 37 IOAEs were recorded in 34 (30.1%) patients (22 CAAAs and 12 TAAAs). Of 37 IOAEs, 15 (40.5%) resulted in no clinical consequence in 15 patients; 17 (45.9%) were responsible for moderate to severe complications in 16 patients, and five (13.5%) led to death in four patients. The composite end point death/nonfatal moderate to severe complication occurred more frequently in patients with IOAEs compared with patients without IOAEs (20 of 34 vs 12 of 79; P < .0001). CONCLUSIONS: In this contemporary series, IOAEs were relatively frequent during branched or fenestrated stenting procedures and were often responsible for significant complications.
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Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Torácica , Aortografia , Prótese Vascular , Procedimentos Endovasculares , Humanos , Complicações Pós-Operatórias , Reoperação , Stents , Resultado do TratamentoRESUMO
Hybrid aortic surgery combining visceral debranching and stent grafting is an alternative to conventional open surgery and branched stent grafting for thoracoabdominal aneurysm repair. Visceral aortic branch bypasses are usually performed from the iliac arteries or the infrarenal or ascending aorta. Herein, we describe a new debranching technique to treat a painful Crawford type III thoracoabdominal aneurysm in a high-risk patient who was deemed unsuitable for open, endovascular, or traditional hybrid repair. The superior mesenteric artery and the right renal arteries were exposed via a right retroperitoneal approach and revascularized from the right axillary artery. Splenic and left renal arteries were exposed via a left retroperitoneal approach and revascularized from the left axillary artery.