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1.
Kidney Int ; 105(1): 84-98, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37839695

RESUMO

Clinical verification of adoptively transferred regulatory T cell (Treg) efficacy in transplantation remains challenging. Here, we examined the influence of autologous ex vivo-expanded polyclonal Tregs on kidney graft survival in a clinically relevant non-human primate model. Peripheral blood Tregs were isolated and expanded using artificial antigen presenting cells. Immunosuppression was comprised of tapered tacrolimus and CTLA4 immunoglobulin, in five animals each without or with Treg infusions. Escalating Treg doses were administered 6, 10, 13, 16, 20, 23, 27 and 30 days after transplant. Infused Tregs were monitored for Treg signature, anti-apoptotic (Bcl-2) and proliferation (Ki67) marker expression. Treg infusions prolonged median graft survival time significantly from 35 to 70 days. Treg marker (Ki67 and Bcl-2) expression by infused Tregs diminished after their infusion but remained comparable to that of circulating native Tregs. No major changes in circulating donor-reactive T cell responses or total Treg percentages, or in graft-infiltrating T cell subsets were observed with Treg infusion. However, Treg infusion was associated with significant increases in CD163 expression by circulating HLA-DR+ myeloid cells and elevated levels of circulating soluble CD163. Further, graft-infiltrating CD163+ cells were increased with Treg infusion. Thus, multiple Treg infusions were associated with M2-like myeloid cell enhancement that may mediate immunomodulatory, anti-inflammatory and graft reparative effects.


Assuntos
Primatas , Linfócitos T Reguladores , Animais , Antígeno Ki-67/metabolismo , Rim , Aloenxertos , Células Mieloides , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
2.
Ann Surg Oncol ; 31(2): 818-826, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37989955

RESUMO

BACKGROUND: The assessment of muscle mass loss, muscle strength, and physical function has been recommended in diagnosing sarcopenia. However, only muscle mass has been assessed in previous studies. Therefore, this study investigated the effect of comprehensively diagnosed preoperative sarcopenia on the prognosis of patients with esophageal cancer. METHODS: The study analyzed 115 patients with esophageal cancer (age ≥ 65 years) who underwent curative esophagectomy. Preoperative sarcopenia was analyzed using the skeletal mass index (SMI), handgrip strength, and gait speed based on the Asian Working Group for Sarcopenia 2019 criteria. Clinicopathologic factors, incidence of postoperative complications, and overall survival (OS) were compared between the sarcopenia and non-sarcopenia groups. The significance of the three individual parameters also was evaluated. RESULTS: The evaluation identified 47 (40.9%) patients with low SMI, 31 (27.0%) patients with low handgrip strength, and 6 (5.2%) patients with slow gait speed. Sarcopenia was diagnosed in 23 patients (20%) and associated with older age and advanced pT stage. The incidence of postoperative complications did not differ significantly between the two groups. Among the three parameters, only slow gait speed was associated with Clavien-Dindo grade 2 or greater complications. The sarcopenia group showed significantly worse OS than the non-sarcopenia group. Those with low handgrip strength tended to have worse OS, and those with slow gait speed had significantly worse OS than their counterparts. CONCLUSIONS: Preoperative sarcopenia diagnosed using skeletal muscle mass, muscle strength, and physical function may have an impact on the survival of patients with esophageal cancer.


Assuntos
Neoplasias Esofágicas , Sarcopenia , Humanos , Idoso , Sarcopenia/etiologia , Sarcopenia/diagnóstico , Força da Mão , Força Muscular/fisiologia , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Prognóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Músculos/patologia , Músculo Esquelético/patologia
3.
Ann Surg Oncol ; 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39269634

RESUMO

BACKGROUND: Whether radiation should be added to neoadjuvant treatment remains controversial, and liquid biopsy has not been reported to predict radioresistance in pancreatic cancer (PC). We aimed to identify microRNAs (miRNAs) governing radioresistance in PC by utilizing peripheral plasma exosome samples and to verify their usefulness as biomarkers. METHODS: miRNA microarray analysis was conducted using pretreatment peripheral plasma exosomes from 10 patients with PC receiving neoadjuvant chemoradiotherapy (NACRT) in the discovery cohort. Patients were categorized into two groups (good and poor responders) based on treatment responses, and candidate miRNAs exhibiting differential expression between the two groups were identified. The radiosensitivity of PC cells was examined after miR-6855-5p overexpression. Next-generation sequencing (NGS) and TargetScan were used to explore the mechanisms of radioresistance. We investigated the correlation between miR-6855-5p expression levels in the pretreatment peripheral plasma exosomes of 28 patients in the validation cohort and the response to NACRT. RESULTS: miR-6855-5p expression was higher in poor responders than in good responders. miR-6855-5p induces radioresistance in PC cells. NGS showed that epithelial-mesenchymal transition (EMT) was involved in miR-6855-5p-related radioresistance. Forkhead box protein A1 (FOXA1) was identified as a direct target of miR-6855-5p using NGS and TargetScan. Clinical examination of samples from the validation cohort revealed a tendency for patients with higher expression of miR-6855-5p in peripheral plasma exosomes to exhibit increased radioresistance (r = -0.5964). CONCLUSIONS: miR-6855-5p regulates the radioresistance of PC by inducing EMT via suppressing FOXA1, and miR-6855-5p in peripheral plasma exosomes may be a biomarker for radioresistance of PC.

4.
Ann Surg Oncol ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39299990

RESUMO

The efficacy of preoperative treatment for pancreatic cancer (PC) has been reported in randomized controlled trials, but the optimal regimen and the appropriateness of combining radiotherapy remain controversial. Therefore, predicting the efficacy of preoperative treatment using biomarkers and determining whether to combine chemotherapy or radiotherapy based on the biology of individual tumors could help personalize treatment and maximize therapeutic outcomes. In this study, a microRNA (miRNA) microarray analysis was performed using peripheral blood plasma exosomes from 10 PC patients who underwent neoadjuvant chemoradiotherapy, leading to the identification of miR-6855-5p as a candidate miRNA. miR-6855-5p was found to induce radioresistance in PC cells. In another cohort of 28 patients, it was observed that those with higher expression levels of miR-6855-5p in peripheral blood plasma exosomes tended to have increased radioresistance (r = - 0.5964). In future, measuring plasma exosomal miR-6855-5p before treatment could potentially lead to precision medicine by personalizing the decision of whether to include radiotherapy in the treatment plan.

5.
Pancreatology ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39278808

RESUMO

BACKGROUND/OBJECTIVES: MicroRNAs (miRNAs) are involved in chemosensitivity through their biological activities in various malignancies, including pancreatic cancer (PC). However, single-miRNA models offer limited predictability of treatment response. We investigated whether a multiple-miRNA prediction model optimized via machine learning could improve treatment response prediction. METHODS: A total of 20 and 66 patients who underwent curative resection for PC after gemcitabine-based preoperative treatment were included in the discovery and validation cohorts, respectively. Patients were classified according to their response to preoperative treatment. In the discovery cohort, miRNA microarray and machine learning were used to identify candidate miRNAs (in peripheral plasma exosomes obtained before treatment) associated with treatment response. In the validation cohort, miRNA expression was analyzed using quantitative reverse transcription polymerase chain reaction to validate its ability to predict treatment response. RESULTS: In the discovery cohort, six and three miRNAs were associated with good and poor responders, respectively. The combination of these miRNAs significantly improved predictive accuracy compared with using each single miRNA, with area under the curve (AUC) values increasing from 0.485 to 0.672 to 0.909 for good responders and from 0.475 to 0.606 to 0.788 for poor responders. In the validation cohort, improved predictive performance of the miRNA combination over single-miRNA prediction models was confirmed, with AUC values increasing from 0.461 to 0.669 to 0.777 for good responders and from 0.501 to 0.556 to 0.685 for poor responders. CONCLUSIONS: Peripheral blood miRNA profiles using an optimized combination of miRNAs may provide a more advanced prediction model for preoperative treatment response in PC.

6.
J Surg Oncol ; 130(3): 504-515, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39099198

RESUMO

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the prognostic value of aberrant right hepatic artery (A-RHA) involvement in patients with pancreatic cancer (PC). METHODS: This study enrolled 474 patients who underwent upfront pancreatectomy or neoadjuvant treatment for resectable (R) or borderline resectable (BR) PC from four institutions. The patients were divided into three groups: A-RHA involvement group (n = 12), patients who had sole A-RHA involvement without major arterial involvement; BR-A group (n = 104), patients who had major arterial involvement; R/BR-PV group (n = 358), others. RESULTS: All patients in the A-RHA involvement group underwent margin-negative resection. The median overall survival of the entire cohort in the A-RHA involvement, R/BR-PV, and BR-A groups was 41.2, 33.5, and 25.2 months, respectively. Although survival in the R/BR-PV group was significantly more favorable than that in the BR-A group (p = 0.0003), no significant difference was observed between the A-RHA involvement group and the R/BR-PV (p = 0.7332) and BR-A (p = 0.1485) groups. CONCLUSIONS: The prognosis of patients with PC and sole A-RHA involvement was comparable to that of patients with R/BR-PV.


Assuntos
Artéria Hepática , Pancreatectomia , Neoplasias Pancreáticas , Humanos , Artéria Hepática/patologia , Artéria Hepática/cirurgia , Artéria Hepática/anormalidades , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/mortalidade , Feminino , Masculino , Estudos Retrospectivos , Prognóstico , Idoso , Pessoa de Meia-Idade , Taxa de Sobrevida , Adulto , Seguimentos , Terapia Neoadjuvante , Idoso de 80 Anos ou mais
7.
Langenbecks Arch Surg ; 409(1): 302, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39377937

RESUMO

BACKGROUND: The clinical significance of the lymph node ratio (LNR), the number of metastatic lymph nodes per dissected lymph node, has not been sufficiently clarified in ampullary cancer. METHODS: Among patients diagnosed histopathologically with ampullary cancer between 1980 and 2018, the study included 106 who underwent pathological radical resection by pancreaticoduodenectomy. The relationships between the LNR and metastatic lymph node sites and prognosis were examined. RESULTS: Multivariate analysis revealed that sex and lymph node metastasis were independent prognostic factors. In the 46 patients (43%) with metastatic lymph nodes, the LNR in the recurrence group was significantly higher than that in the non-recurrence group (0.15 ± 0.11 vs. 0.089 ± 0.071, p = 0.025). The receiver operating characteristic curve demonstrated that the LNR cut-off value, 0.07 (area under the curve = 0.70, sensitivity 81%, specificity 56%), was a significant indicator for recurrence (22% vs. 61%, p = 0.016) and prognosis (5-year survival: 48% vs. 83%, p = 0.028). Among the metastatic lymph node sites in the 46 positive cases, lymph node metastases developed from the peripancreatic head region (80%, 37/46) to the superior mesenteric artery (33%, 15/46) and para-aortic (11%, 5/46) regions. CONCLUSION: Lymph node metastasis is an independent prognostic factor, and the LNR is a significant indicator for recurrence and prognosis in patients with ampullary cancer.


Assuntos
Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Razão entre Linfonodos , Metástase Linfática , Recidiva Local de Neoplasia , Pancreaticoduodenectomia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Idoso , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias do Ducto Colédoco/patologia , Neoplasias do Ducto Colédoco/mortalidade , Metástase Linfática/patologia , Prognóstico , Adulto , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Relevância Clínica
8.
Oncology ; 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38052183

RESUMO

INTRODUCTION: Metastatic or unresectable locally advanced oesophageal cancer remains a disease with high mortality. More recently, pembrolizumab plus chemotherapy has been indicated as the first-line treatment for those patients, but the predictive factors for treatment efficacy remain controversial. This study investigated the clinical utility of early tumour shrinkage (ETS) and depth of response (DpR) in metastatic or unresectable oesophageal cancer treated with pembrolizumab plus CF therapy. METHODS: ETS and DpR, defined as the percent decreases at the second evaluation and the percentage of the maximal tumour shrinkage during treatment, were measured in 53 eligible patients. The ETS and DpR cut-off values were 20% and 30%, respectively, based on survival outcomes. RESULTS: Twenty-seven patients (51%) were treatment-naïve, while 26 (49%) had received any treatment before initiating pembrolizumab plus CF therapy. The median progression-free survival (PFS) and overall survival (OS) for ETS ≥20% and <20% were 12.7 and 5.5 months and 14.4 and 8.2 months, and 12.7 and 4.9 months and 14.4 and 8.0 months for DpR ≥30% and <30%, respectively. ETS <20% showed early tumour growth, whereas ETS ≥20% had a good response rate with sufficient longer response duration. In addition, an ETS cut-off of 20% predicted the best overall response and was not associated with prior treatment. In multivariable analysis, ETS ≥20% and DpR ≥30% were independent factors of longer PFS. CONCLUSION: Our findings suggest that an ETS is a promising on-treatment marker for early prediction of further sensitivity to pembrolizumab plus CF therapy.

9.
Ann Surg Oncol ; 29(2): 935-944, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34586524

RESUMO

BACKGROUND: F-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) has been used to diagnose and stage various cancers. In regard to biliary tract cancer (BTC), due to cholangitis it is difficult to evaluate FDG uptake caused by cancer. We previously showed that FDG-positive lymph nodes (LNs) of resectable BTC had a possibility of predicting postoperative prognosis. OBJECTIVE: This study aimed to validate the usability of FDG-PET for LNs using another cohort and to investigate in detail the relationship between FDG-positive LNs and the prognosis of BTC. METHODS: We measured the preoperative maximum standardized uptake value (SUVmax) at each of the 190 surgically dissected LN areas in 67 patients and investigated the prognosis using our previously determined SUVmax cut-off values of ≥ 2.8. RESULTS: Regarding the prognosis of patients with resectable BTC, a LN SUVmax ≥ 2.8 [PET N (+)] was a poor prognostic factor for recurrence-free survival (RFS) compared with a LN SUVmax < 2.8 [PET N (-)]. It was confirmed that the hazard ratio forest plot [PET N (+)/PET N (-)] for RFS indicated a similar tendency among subcategories. Moreover, we investigated patients with pN0 disease and demonstrated that the PET N (+) group also had a significantly worse RFS outcome compared with the PET N (-) group. Recurrence of the PET N (+) group has significantly occurred more often in LNs than that of the PET N (-) group. CONCLUSION: High LN SUVmax was confirmed to be the preoperatively diagnosed prognostic risk factor for RFS in resectable BTC and could be helpful for clinical decision making regarding the perioperative treatment strategy.


Assuntos
Neoplasias do Sistema Biliar , Fluordesoxiglucose F18 , Neoplasias do Sistema Biliar/diagnóstico por imagem , Neoplasias do Sistema Biliar/cirurgia , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos
10.
Cancer Sci ; 111(2): 323-333, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31799781

RESUMO

CXCL9, an IFN-γ inducible chemokine, has been reported to play versatile roles in tumor-host interrelationships. However, little is known about its role in intrahepatic cholangiocarcinoma (iCCA). Here, we aimed to elucidate the prognostic and biological implications of CXCL9 in iCCA. Endogenous CXCL9 expression and the number of tumor-infiltrating lymphocytes were immunohistochemically assessed in resection specimens. These data were validated in mice treated by silencing CXCL9 with short hairpin RNA. In addition, the induction of endogenous CXCL9 and the effects of CXCL9 on tumor biological behaviors were evaluated in human cholangiocarcinoma cell lines. Immunohistochemical analyses revealed that high CXCL9 expression was closely correlated with prolonged postoperative survival and a large number of tumor-infiltrating natural killer (NK) cells. In fact, due to the trafficking of total and tumor necrosis factor-related apoptosis-inducing ligand-expressing NK cells into tumors, CXCL9-sufficient cells were less tumorigenic in the liver than CXCL9-deficient cells in mice. Although CXCL9 involvement in tumor growth and invasion abilities differed across cell lines, it did not exacerbate these abilities in CXCL9-expressing cell lines. We showed that CXCL9 was useful as a prognostic marker. Our findings also suggested that CXCL9 upregulation might offer a therapeutic strategy for treating CXCL9-expressing iCCA by augmenting anti-tumor immune surveillance.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Quimiocina CXCL9/metabolismo , Colangiocarcinoma/patologia , Células Matadoras Naturais/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Animais , Neoplasias dos Ductos Biliares/imunologia , Neoplasias dos Ductos Biliares/cirurgia , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Quimiocina CXCL9/antagonistas & inibidores , Colangiocarcinoma/imunologia , Colangiocarcinoma/cirurgia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Prognóstico , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/farmacologia , Regulação para Cima
11.
Ann Surg Oncol ; 27(2): 610-619, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31605325

RESUMO

BACKGROUND: CD36, a multi-ligand scavenger receptor, has been associated with several cancers. Many studies have revealed that CD36 contributed to cancer malignancy. This study aimed to reveal the function of CD36 expression in pancreatic ductal adenocarcinoma (PDAC). METHODS: CD36 expression was characterized using immunohistochemistry in 95 clinical specimens resected from patients with PDAC. We divided patients into two groups, with different CD36 expression levels, and analyzed and compared their prognoses. CD36 expression was also assessed in PDAC cell lines. Gemcitabine-resistant (GR) PDAC cell lines were transfected with small interfering RNA (siRNA) that specifically targeted CD36 to evaluate chemoresistance and apoptosis. RESULTS: In resected PDAC samples, CD36 expression was significantly correlated with microinvasion into the venous system (p = 0.0284). Patients with high CD36 expression had significantly lower overall survival (OS) and recurrence-free survival (RFS) rates than patients with low expression; thus, CD36 was an independent prognostic factor for OS and RFS. In subgroup analyses, CD36 was an independent risk factor for OS and RFS in 59 patients treated with gemcitabine adjuvant chemotherapy. CD36 expression was upregulated in PDAC-GR cell lines compared with the PDAC parent cell line. Transduction with siRNA downregulated CD36, which reduced PDAC cell resistance to gemcitabine and inhibited anti-apoptosis proteins. CONCLUSION: CD36 expression influenced gemcitabine resistance by regulating anti-apoptosis proteins. High CD36 expression was a significant, unfavorable prognostic factor in PDAC. Anti-CD36 treatment might serve as an optional treatment for lowering resistance to gemcitabine.


Assuntos
Apoptose , Biomarcadores Tumorais/metabolismo , Antígenos CD36/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Antimetabólitos Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Biomarcadores Tumorais/genética , Antígenos CD36/antagonistas & inibidores , Antígenos CD36/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Desoxicitidina/farmacologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Ensaios Clínicos Controlados não Aleatórios como Assunto , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Prognóstico , RNA Interferente Pequeno/genética , Estudos Retrospectivos , Taxa de Sobrevida , Células Tumorais Cultivadas , Gencitabina , Neoplasias Pancreáticas
12.
Dig Dis Sci ; 65(10): 2937-2948, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31853779

RESUMO

BACKGROUND/AIM: We previously demonstrated that inflammatory cytokine interleukin-6 (IL-6) was produced during cancer progression, worked together with transforming growth factor-beta 1 (TGF-ß1), and induced the epithelial-mesenchymal transition (EMT) with chemo-resistance against gemcitabine (GR) at the invasion front of biliary tract cancers (BTCs). However, the significance of cytokine-induced T cell accumulation at the tumor microenvironment in biliary tract cancer (BTC) is not well understood. Because these cytokines (IL-6 and TGF-ß1) are able to differentiate naïve T cells into Foxp3-expressing T cells (Tregs) and/or IL-17-producing T helper 17 (Th17) cells, we investigated the relationship between heterogeneous, cancer-producing cytokines and T cell differentiation. METHODS: In total, 127 curative resected specimens from patients with BTCs at Osaka University Hospital between 2000 and 2012 were evaluated for IL-6, TGF-ß1, Tregs, and Th17 cells by immunohistochemistry. The ability of BTC-GR cells to undergo T cell differentiation was investigated in vitro. RESULTS: Tregs accumulated at the tumor center and Th17 cells accumulated at the invasion front during cancer progression and/or metastasis; each signaled poor prognosis. Treg accumulation was related to TGF-ß1 expression by cancer cells, and Th17 cell accumulation was related to IL-6 expression by cancer cells, in resected specimens; this was confirmed in vitro. Compared with parent cells, GR cells produced IL-6 but not TGF-ß1 in a time-dependent manner, had EMT features, and induced T cell differentiation to Th17 cells but not Tregs. CONCLUSION: Cytokines produced by cancer cells (IL-6 and TGF-ß1) induced heterogeneity of Tregs and Th17 cells in the tumor microenvironment, supporting progression of BTC.


Assuntos
Neoplasias do Sistema Biliar/metabolismo , Diferenciação Celular , Citocinas/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/imunologia , Neoplasias do Sistema Biliar/patologia , Células Cultivadas , Técnicas de Cocultura , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Fator de Crescimento Transformador beta1/metabolismo , Microambiente Tumoral , Gencitabina
13.
Dig Dis Sci ; 64(3): 792-802, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30465177

RESUMO

PURPOSE: In this study, we aim to clarify whether exosomes secreted from hepatocellular carcinoma (HCC) cells under hypoxia affect angiogenesis in endothelial cells. METHODS: Exosomes derived from human liver cancer cell lines were cultured under hypoxic or normoxic conditions for 24 h, isolated using ExoQuick-TC®, and co-cultured with HUVECs to evaluate angiogenic activity. We also evaluated the expression of miR-155 in the exosomes from 40 patients with HCC. RESULTS: Exosomes under hypoxia remarkably enhanced tube formation of HUVECs. Both cellular and exosomal miR-155 were significantly up-regulated under hypoxic conditions. Knockdown of miR-155 in HCC cells attenuated the promotion of tube formation by exosomes under hypoxia in HUVECs, and high expression of exosomal miR-155 in preoperative plasma was significantly correlated with early recurrence. CONCLUSION: These results suggest that exosomes derived from HCC cells under hypoxia induce tube formation of HUVECs and that exosomal miR-155 may affect angiogenic activity in HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Exossomos/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Neoplasias Hepáticas/metabolismo , Neovascularização Fisiológica , Hipóxia Tumoral , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Exossomos/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neovascularização Patológica , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo
14.
Gan To Kagaku Ryoho ; 45(2): 359-361, 2018 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-29483447

RESUMO

A 60-year-old man underwent palliative surgery with a diagnosis of unresectable cancer, and he visited our hospital for further treatment. Since the cancer was unresectable and multiple hepatic tumors were revealed in CT images that were not metastases, we decided to perform curative surgery for the pancreatic cancer accompanied by partial liver invasion. Pancreaticoduodenectomy plus partial hepatectomy were performed, and 2 tumors were detected in the resected specimen: one in the pancreas-duodenum region and a submucosal tumor in the duodenum bulb. The large tumor that occupied the pancreasduodenum region was histologically diagnosed as an undifferentiated carcinoma, and the duodenal submucosal tumor was consistent with findings of a poorly differentiated adenocarcinoma. Two years after surgery, CT examination revealed a mass extending into the inferior vena cava(IVC)from near the right renal vein. We eventually diagnosed lymph node recurrence with tumor thrombosis inthe IVC and started chemotherapy(FOLFIRINOX). After the tumor decreased, we performed salvage surgery involving resection of the lymph node, thrombectomy, and right nephrectomy. The tumor revealed atypical cells in the region of thrombosis, and the pathological findings were not in conflict with the findings of metastases from pancreatic cancer 2 years prior. After the treatment, chemotherapy was administered and he survived without any recurrence for 15 months after surgery.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias Pancreáticas/patologia , Veia Cava Inferior , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/secundário , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/irrigação sanguínea , Neoplasias Pancreáticas/cirurgia , Recidiva , Veia Cava Inferior/patologia
17.
Gan To Kagaku Ryoho ; 42(12): 1530-2, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26805086

RESUMO

For patients with Stage Ⅳ colorectal cancer, primary site resection improves survival and relieves symptoms of bleeding and obstruction by the primary lesion. Laparoscopic surgery is thought to be useful for Stage Ⅳ colorectal cancer because of its low aggressiveness and the short recovery time. We examined the usefulness of laparoscopic resection of primary lesions for Stage Ⅳ colon cancer patients. Forty-one cases of Stage Ⅳ colorectal cancer treated by resection of the primary lesion were investigated, and we compared the group of patients with laparoscopic surgery (LAC) to the group of patients with open laparotomy (OP). The LAC Group was superior to the OP Group from the viewpoint of blood loss, days of hospitalization, and length of time from operation to start of chemotherapy. For Stage Ⅳ colorectal cancer, laparoscopic resection of the primary lesion is thought to be a useful method to reduce the invasiveness of treatment.


Assuntos
Neoplasias Colorretais/cirurgia , Laparoscopia , Idoso , Colectomia , Neoplasias Colorretais/patologia , Feminino , Humanos , Tempo de Internação , Masculino , Estadiamento de Neoplasias , Resultado do Tratamento
18.
Gan To Kagaku Ryoho ; 42(12): 1683-5, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26805137

RESUMO

Recently, self-expanding metallic stent (SEMS) have been found to be useful for treatment of intestinal obstruction by colorectal cancer, either as a bridge to surgery or terminal treatment. When SEMS are used for patients in the terminal stage with obstruction due to colorectal cancer, re-obstruction is a severe problem. We report 2 cases of re-insertion of SEMS for obstruction of colon cancer after the first insertion of SEMS. No major problems occurred in either the 2 cases. In the first case, the patient suffered from re-obstruction of colon cancer 6 months after the first SEMS treatment and died 9 months after the second SEMS treatment. In the second case, the patient suffered from re-obstruction of colon cancer 5 months after the first SEMS treatment and died 7 months after the second SEMS treatment. Re-insertion of SEMS for a second obstruction due to colorectal cancer after SEMS treatment is useful for terminal treatment for maintaining QOL.


Assuntos
Neoplasias Colorretais/terapia , Íleus/terapia , Stents Metálicos Autoexpansíveis , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/complicações , Feminino , Humanos , Íleus/etiologia , Masculino , Cuidados Paliativos , Qualidade de Vida , Resultado do Tratamento
19.
Gan To Kagaku Ryoho ; 42(12): 1941-3, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26805224

RESUMO

We experienced a rare case of liposarcoma that we were able to remove laparoscopically based on a preoperative diagnosis. The patient in this case was a 67-year-old woman. Abdominal CT and pelvic MRI showed a mass of 15 cm in diameter on the left side of the pelvis. Well-differentiated liposarcoma was diagnosed based on these images. Based on imaging findings, the possibility of permeation to the neighboring organs was considered to be low, and so the operation was performed laparoscopically. The location of the tumor was similar to that seen during preoperative imaging diagnosis, and we were able to remove it laparoscopically without resecting the organ. The postoperative progress was good, and the patient left the hospital on the fourth postoperative day. This case shows how with detailed preoperative imaging, a minimally invasive approach is possible for the treatment of liposarcoma.


Assuntos
Lipossarcoma/cirurgia , Neoplasias Retroperitoneais/cirurgia , Idoso , Feminino , Humanos , Laparoscopia , Imageamento por Ressonância Magnética , Imagem Multimodal , Neoplasias Retroperitoneais/patologia , Tomografia Computadorizada por Raios X
20.
Gan To Kagaku Ryoho ; 41(12): 1586-8, 2014 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-25731261

RESUMO

Ileus due to colon cancer often develops from a timing and the method of the operation and perioperative care, comparing with ordinary cases. The use of self-expanding metallic stent (SEMS) was first authorized by insurance and became available nationwide in Japan in 2012. Insertion of SEMS for ileus due to colorectal cancer is useful as a bridge to surgery (BTS) approach and releases stenosis as palliative care. Here we report 5 successful cases of anastomosis performed during a laparoscopic operation for ileus due to colorectal cancer after BTS using SEMS. Successful SEMS insertion for colon cancer ileus enables observation of the proximal side. Because the decompression efficiency with SEMS is high, laparoscopic surgery becomes possible. SEMS insertion as a BTS is useful for ileus due to colorectal cancer.


Assuntos
Neoplasias Colorretais/cirurgia , Íleus/cirurgia , Stents , Idoso , Neoplasias Colorretais/complicações , Feminino , Humanos , Íleus/etiologia , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Complicações Pós-Operatórias
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