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1.
Int J Colorectal Dis ; 34(10): 1731-1739, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31478086

RESUMO

BACKGROUND: Angiotensin signaling is suggested to be involved in tumorigenesis, tumor proliferation, and metastases. In colorectal cancer (CRC), it was demonstrated that angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may reduce the risk of CRC; however, their impact on tumor recurrence remains unknown. Therefore, in this study, we evaluated the impact of ACEIs/ARBs on tumor recurrence in CRC patients. PATIENTS AND METHODS: We retrospectively investigated the clinicopathological data of 461 stage I-III CRC patients. We divided the patients into those who took an ACEI and/or ARB (the ACEI/ARB+ group) and those who did not (the ACEI/ARB- group), and we compared the two groups' recurrence-free survival (RFS) using a Kaplan-Meier curve analysis and log rank test. We also examined the impact of AGTR1 expression on tumor recurrence, using two public CRC datasets. RESULTS: The Kaplan-Meier curves showed a trend toward improved RFS in the ACEI/ARB+ group versus the ACEI/ARB- group (p = 0.063). Subgroup analyses demonstrated that the RFS was significantly better in the ACEI/ARB+ group versus the ACEI/ARB- group in the patients with left-sided CRC (p = 0.030) and those with stage I CRC (p = 0.009). Consistent with these findings, the AGTR1 expression was higher in the left-sided versus right-sided colon (p = 0.048). High AGTR1 expression levels were associated with poor RFS in the GSE39582 dataset's stage I-III CRC patients (p < 0.001), and this finding was also validated in the GSE17536 dataset (p = 0.023). CONCLUSION: ACEI/ARB treatment may reduce tumor recurrence in left-sided CRC and early-stage CRC.

2.
Gan To Kagaku Ryoho ; 46(9): 1361-1366, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31530771

RESUMO

This year, the genetic testing for cancer genome medicine approved in Japan, and the clinical basis for this medical area is developed. Focus will likely fall not only on genetic analysis in tissues, but also on genomic analysis by liquid biopsy using patient body fluids such as blood, saliva and urine. The advantages of liquid biopsy are the fact that it is minimally invasive and the possibility of broadening the diagnosis and selection of therapeutic agents, even in cases in which it is difficult to collect tumor tissues. Liquid biopsies of cancer patients will enable, circulating tumor cell(CTC), cell free DNA(cfDNA), circulating tumor cell DNA(ctDNA), exosomes and microRNA(miRNA). The potential usefulness of liquid biopsy for cancer diagnosis, recurrence prediction and monitoring of treatment effect has been mentioned in various manuscripts. In immunotherapy, liquid genetic biomarkers for predicting the therapeutic effect of immune checkpoint inhibitors are under development worldwide. Although issues such as standardization of the measurement methods and the samples used remain, early diagnosis of cancer by liquid biopsy may become a reality in the near future.


Assuntos
Genômica , Biomarcadores Tumorais , Humanos , Imunoterapia , Japão , Biópsia Líquida , Recidiva Local de Neoplasia
3.
Int J Colorectal Dis ; 34(8): 1491-1496, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31309326

RESUMO

PURPOSE: The increased incidence of colorectal cancer (CRC) has necessitated the development of novel prognostic and predictive factors from which new diagnostic tests could evolve. Evidence suggests the KRAS gene represents such a factor; its mutations are considered to be early indicators of CRC progression. This study assessed the prognostic impact of specific known KRAS codon 12/13 mutations on survival in patients with CRC. METHODS: Formalin-fixed paraffin-embedded tissue blocks or sections from primary were obtained from patients registered between 2014 and 2016 for genomic DNA extraction. KRAS gene was analyzed by direct sequencing or Luminex assay. The primary endpoint was the frequency of KRAS gene mutations and the secondary endpoints were differences in KRAS mutation rates by various stratification factors. Univariate and multivariate analyses were performed to investigate relationships between KRAS mutation rates and patient background factors. RESULTS: Sequencing of 200 CRC primary tumor samples demonstrated 74 (37.5%) with KRAS mutations in codons 12 (77%; 57/74) and 13 (23%; 17/74), all of which were TNM stages I-III. Tumors with KRAS mutations were more frequently located in the right side of the colon. Multivariate analysis indicated that G12V or G12C mutations were associated with poor prognosis [hazard ratio (HR) = 3.77, 95% confidence interval (CI), 1.54-8.39 and HR = 6.57; 95% CI, 1.90-17.7, respectively] in terms of recurrence-free survival. CONCLUSION: KRAS codon 12G-to-V or G-to-C mutations are independent prognostic factors in patients with stage I-III CRC.

5.
Cancer Sci ; 110(3): 1096-1104, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30637877

RESUMO

The silencing of tumor suppressor genes by promoter CpG island (CGI) methylation is an important cause of oncogenesis. Silencing of MLH1 and BRCA1, two examples of oncogenic events, results from promoter CGI methylation. Interestingly, both MLH1 and BRCA1 have a divergent promoter, from which another gene on the opposite strand is also transcribed. Although studies have shown that divergent transcription is an important factor in transcriptional regulation, little is known about its implication in aberrant promoter methylation in cancer. In this study, we analyzed the methylation status of CGI in divergent promoters using a recently enriched transcriptome database. We measured the extent of CGI methylation in 119 colorectal cancer (CRC) clinical samples (65 microsatellite instability high [MSI-H] CRC with CGI methylator phenotype, 28 MSI-H CRC without CGI methylator phenotype and 26 microsatellite stable CRC) and 21 normal colorectal tissues using Infinium MethylationEPIC BeadChip. We found that CGI within divergent promoters are less frequently methylated than CGI within unidirectional promoters in normal cells. In the genome of CRC cells, CGI within unidirectional promoters are more vulnerable to aberrant methylation than CGI within divergent promoters. In addition, we identified three DNA sequence motifs that correlate with methylated CGI. We also showed that methylated CGI are associated with genes whose expression is low in normal cells. Thus, we here provide fundamental observations regarding the methylation of divergent promoters that are essential for the understanding of carcinogenesis and development of cancer prevention strategies.


Assuntos
Neoplasias Colorretais/genética , Ilhas de CpG/genética , Metilação de DNA/genética , Regiões Promotoras Genéticas/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Instabilidade de Microssatélites , Fenótipo , Transcriptoma/genética
6.
J Hepatobiliary Pancreat Sci ; 26(2): 63-72, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30561106

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with poor prognosis. This is due to late diagnosis and lack of reliable prognostic biomarkers. In this study, we focused on exosomal microRNA (miRNA) in portal vein blood (PVB) as a potential biomarker to identify patients at high-risk for recurrence and poor postoperative outcome. METHODS: Exosomal miR-4525, miR-451a and miR-21 expressions were assessed using PVB and peripheral blood (PB) collected from 55 PDAC patients during curative pancreatectomy. Correlation between the miRNA expressions and clinical outcomes, and target genes expressions was investigated. RESULTS: Exosomal miR-4525, miR-451a and miR-21 levels were upregulated in PVB, which were higher than those in the PB. High expression of miR-4525, miR-451a and miR-21 in PVB was associated with recurrence with a higher sensitivity, specificity, and accuracy than that in PB. Cox regression analysis showed miR-4525, miR-451a and miR-21 levels in PVB were independent prognostic factors for overall survival and disease-free survival. There was a negative correlation between the expressions of miR-4525 and MEN1 mRNA, miR-451a and CAB39 mRNA, and t miR-21 and PDCD4 mRNA. CONCLUSIONS: miR-4525, miR-451a and miR-21 in PVB are potential biomarkers identifying patients at high-risk for recurrence and poor survival in resected PDAC patients.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático/sangue , Exossomos , MicroRNAs/sangue , Neoplasias Pancreáticas/sangue , Veia Porta , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/terapia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Pancreatectomia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Regulação para Cima
7.
Clin Cancer Res ; 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30279230

RESUMO

Purpose: Colorectal cancers with microsatellite instability-high (MSI-H) status, due to mismatch repair deficiency, are associated with poor patient outcomes after relapse. We aimed to identify novel therapeutic targets for them.Experimental Design: We performed MSI analyses of over 2,800 surgically resected colorectal tumors obtained from consecutive patients treated in Japan from 1998 through June 2016. Whole-exome sequencing, transcriptome sequencing, and methylation analyses were performed on 149 of 162 tumors showing MSI in BAT25 and BAT26 loci. We analyzed patient survival times using Bonferroni-adjusted log-rank tests.Results: Sporadic MSI-H colorectal cancers with promoter methylation of MLH1 (called MM) had a clinicopathological profile that was distinct from that of colorectal cancers of patients with germline mutations (Lynch syndrome, LS-associated) or somatic, Lynch-like mutations in mismatch repair genes. MM tumors had more insertions and deletions and more recurrent mutations in BRAF and RNF43 than LS-associated or Lynch-like MSI-H tumors. Eleven fusion kinases were exclusively detected in MM MSI-H colorectal cancers lacking oncogenic KRAS/BRAF missense mutations and were associated with worse post-relapse prognosis. We developed a simple method to identify MM tumors and applied it to a validation cohort of 28 MSI-H colorectal cancers, identifying 16 MM tumors and 2 fusion kinases.Conclusions: We discovered that fusion kinases are frequently observed among sporadic MM MSI-H colorectal cancers. The new method to identify MM tumors enables us to straightforwardly group MSI-H patients into candidates of LS or fusion kinase carriers. Clin Cancer Res; 1-12. ©2018 AACR.

8.
Oncol Lett ; 15(6): 9584-9592, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29805680

RESUMO

Patients diagnosed preoperatively with ductal carcinoma in situ (DCIS) breast cancer have the potential to develop invasive ductal carcinoma (IDC). The present study investigated the usefulness of exosome-encapsulated microRNA-223-3p (miR-223-3p) as a biomarker for detecting IDC in patients initially diagnosed with DCIS by biopsy. The potential association between miR-223-3p and clinicopathological characteristics was examined in patients with breast cancer. Exosomes of 185 patients with breast cancer were separated from plasma by ultracentrifugation. Initially a microRNA (miRNA) microarray was examined to reveal the invasion specific miRNAs using exosomes collected from 6 patients with breast cancer, including 3 DCIS patients, 3 IDC patients and 3 healthy controls. In the miR microarray analysis the miR-223-3p levels of IDC patients demonstrated the highest fold-change compared with those in the DCIS patients and healthy controls. The potential of miR-223-3p for cell proliferation and cell invasion were examined in vitro using MCF7 cells transfected with the miR-223-3p gene. MCF7 cells transfected with the miR-223-3p gene significantly promoted cell proliferation and cell invasive ability (P<0.05). The plasma exosomal miR-223-3p levels of the other 179 patients with breast cancer and 20 healthy controls were measured using TaqMan miR assays. The exosomal miR-223-3p levels of the patients with breast cancer were significantly increased compared with the healthy controls (P<0.01). A statistically significant association was observed between the exosomal miR-223-3p levels and histological type, pT stage, pN stage, pathological stage, lymphatic invasion and nuclear grade (P<0.05). The exosomal miR-223-3p levels of IDC patients (stage I) and upstaged IDC patients (stage I) were significantly higher compared with the DCIS patients (P<0.05). These results suggest that exosomal miR-223-3p may be a useful preoperative biomarker to identify the invasive lesions of DCIS patients diagnosed by biopsy. In addition, plasma exosome-encapsulated miR-223-3p level was significantly associated with the malignancy of breast cancer.

9.
Oncol Rep ; 40(1): 319-330, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29749537

RESUMO

Recently, exosome­encapsulated microRNAs (miRNAs) have been attracting attention as stable and minimally invasive biomarkers in cancer patients. The aim of the present study was to clarify the value of plasma exosomal microRNA­23b (miR­23b) as a diagnostic and prognostic biomarker in gastric cancer (GC) patients at each tumor stage. We first selected recurrence specific exosomal miRNA by miRNA microarray from 6 GC patients (stage I) with or without recurrence, and 3 healthy volunteers. In this analysis, miR­23b demonstrated the most significant change. Subsequently, we validated the usefulness of miR­23b as a biomarker using the plasma exosome samples collected from 232 GC patients and 20 healthy volunteers. miR­23b levels were evaluated by Taqman microRNA assays. Exosomal miR­23b levels of GC patients were significantly lower than those of the healthy controls. A significant association was revealed between the plasma exosomal miR­23b levels and the expression of miR­23b in primary tumor tissues. Concerning the pathological condition, miR­23b demonstrated a significant association with tumor size, depth of invasion, liver metastasis and TNM stage. The overall survival (OS) rates of low­miR­23b patients were significantly worse than those of high­miR­23b patients at stage I, II, III and IV. The disease­free survival (DFS) rates of low exosomal miR­23b patients were significantly worse than those of high­miR­23b patients at stage I, II and III. Cox multivariate analysis indicated that exosomal miR­23b was an independent prognostic factor for OS and DFS at each tumor stage. Our results revealed that exosomal miR­23b has potential as minimally invasive predictive biomarker for the recurrence and prognosis of GC in patients at all stages.


Assuntos
Biomarcadores Tumorais/genética , MicroRNAs/genética , Prognóstico , Neoplasias Gástricas/genética , Idoso , Intervalo Livre de Doença , Exossomos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Gástricas/patologia
10.
Oncology ; 94(5): 311-323, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29533963

RESUMO

OBJECTIVES: The aim of this study was to clarify the usefulness of plasma exosomal microRNA-451a (miR-451a) as a novel biomarker for the early prediction of recurrence and prognosis in non-small cell lung cancer (NSCLC) patients after curative resection. METHODS: Before surgery, plasma samples were collected and exosomal microRNA (miRNA) levels were evaluated. We first profiled specific exosomal miRNAs related to recurrence in 6 NSCLC patients with stage IA cancer by miRNA microarray. We then validated the usefulness of selected miRNAs as biomarkers using the other 285 NSCLC patients. RESULTS: Plasma exosomal miR-451a showed the highest upregulation in the NSCLC patients with recurrence in the miRNA microarray analysis. A significant positive correlation was demonstrated between exosomal miR-451a levels and NSCLC tissue miR-451a levels. Exosomal miR-451a showed a significant association with lymph node metastasis, vascular invasion, and stage. In stage I, II, or III patients, the overall survival (OS) and disease-free survival (DFS) rates among the high-exosomal-miR-451a patients were significantly worse than those among the low-exosomal-miR-451a patients. In Cox multivariate analysis, exosomal miR-451a showed significance for OS and DFS. CONCLUSION: Plasma exosomal miR-451a might serve as a reliable biomarker for the prediction of recurrence and prognosis in NSCLC patients with stage I, II, or III cancer.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/fisiopatologia , Masculino , MicroRNAs/sangue , MicroRNAs/genética , Análise em Microsséries , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Valor Preditivo dos Testes , Prognóstico
11.
J Hepatobiliary Pancreat Sci ; 25(2): 155-161, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29130611

RESUMO

BACKGROUND: MicroRNAs (miRNAs) encapsulated in the exosomes of plasma is of interest as stable and minimally invasive biomarkers for recurrence and prognosis in cancer patients. The aim of this study was to clarify the predictive and prognostic value of plasma exosomal microRNA-451a (miR-451a) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Microarray-based expression profiling of miRNAs derived from exosomes in the plasma of six PDAC patients with UICC stage II was employed to identify a biomarker to distinguish between patients with and without recurrence. For validation analysis, plasma exosome samples of other 50 PDAC patients were measured by TaqMan MicroRNA assays. RESULTS: In the miRNA microarray analyses, miR-451a showed the highest upregulation in the stage II patients who showed recurrence after surgery. In the relationship to pathological factors, exosomal miR-451a showed a significant association with tumor size and stage. The overall survival (OS) and disease-free survival rates (DFS) of the high exosomal miR-451a patients were significantly worse than those of the low miR-451a patients. In Cox proportional hazards model analysis, exsomal miR-451a showed significance to OS and DFS. CONCLUSIONS: Plasma exosomal miR-451a levels may be a useful minimally invasive biomarker for the prediction of recurrence and prognosis in PDAC patients.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , MicroRNAs/genética , Recidiva Local de Neoplasia/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/fisiopatologia , Estudos de Casos e Controles , Intervalo Livre de Doença , Exossomos/genética , Feminino , Regulação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real/métodos , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
12.
Gen Thorac Cardiovasc Surg ; 66(2): 103-107, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29101533

RESUMO

OBJECTIVE: Polyglycolic acid and oxidized regenerated cellulose have been widely used as a sealant for repairing pulmonary air leakage during respiratory surgery. However, fundamental research of these materials has not been sufficiently conducted. Therefore, we conducted studies to assess the pressure resistance ability of these materials using a canine visceral pleural defect model at the early phase. METHOD: The 6-mm circular defect and the 12-mm square defect were created on the visceral pleura of anesthetized beagles. These defects were then repaired using one of four methods: method A using polyglycolic acid and fibrin glue; method B using oxidized regenerated cellulose and fibrin glue; method C using oxidized regenerated cellulose; method D using fibrin glue. Airway pressure was measured as bursting pressure when air leakage from the repaired areas occurred at 5 min, 3 h, and 24 h after repair. RESULTS: For the 6-mm circle defect, method A showed higher bursting pressures than the other methods at 5 min and 3 h (p < 0.05); method B showed higher than methods C and D at 5 min and 3 h (p < 0.05). For the 12-mm square defect, method A showed higher bursting pressures than the other methods at all time points (p < 0.05). Moreover, method B showed higher than method C at 24 h (p < 0.05). CONCLUSION: Visceral pleural repairs using polyglycolic acid combined with fibrin glue showed the highest bursting pressure. Oxidized regenerated cellulose combined with fibrin glue showed sufficiently high bursting pressure in repair of small 6-mm circular defects.


Assuntos
Curativos Biológicos , Modelos Animais de Doenças , Adesivo Tecidual de Fibrina/uso terapêutico , Pleura/lesões , Ácido Poliglicólico , Enfisema Pulmonar/cirurgia , Adesivos Teciduais/uso terapêutico , Animais , Cães , Feminino , Pneumonectomia , Pneumoperitônio/prevenção & controle , Resultado do Tratamento , Técnicas de Fechamento de Ferimentos
13.
J Thorac Dis ; 9(10): 3766-3773, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29268384

RESUMO

Background: The purpose of this randomized study was to compare the effects of pregabalin with epidural analgesia on early phase post-thoracotomy pain. Methods: This study was conducted on 90 adult patients who underwent thoracotomy. Patients were randomly divided into two groups, an epidural analgesia group, where 45 patients received 0.2% ropivacaine hydrochloride and fentanyl through a thoracic epidural catheter, and a pregabalin group, where 45 patients received 75 mg pregabalin orally twice daily. Both groups were also administered orally with celecoxib along with each treatment. Numerical rating scale (NRS) and sleep interference rate (SIR) were evaluated on the first day, third day, and fifth day after surgery. Anesthetic induction time, operation time, recovery time, the use of additional analgesic drugs and adverse effects were also examined. Results: NRS and SIR were significantly lower in the pregabalin group at all time points (P<0.05). The number of patients requiring additional analgesic drugs within 24 hours after surgery showed no difference between the two groups; however, the number was significantly decreased in the pregabalin group after post-operative day 1 (P<0.001). Adverse effects including pneumonia, dysuria, constipation and nausea were identified among many patients in the epidural analgesia group (P<0.05). Operation time and recovery time were the same for both groups, while the epidural analgesia group showed a significantly longer anesthetic induction time (P<0.001). Conclusions: Pregabalin is considered to be a safe and effective treatment method which is an alternative to epidural analgesia for acute post-thoracotomy pain.

14.
Oncotarget ; 8(45): 78598-78613, 2017 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-29108252

RESUMO

A primary tumor can create a premetastatic niche in distant organs to facilitate the development of metastasis. The mechanism by which tumor cells communicate with host cells to develop premetastatic niches is unclear. We focused on the role of microRNA (miR) signaling in promoting metastasis. Here, we identified miR-203 as a signaling molecule between tumors and monocytes in metastatic colorectal cancer (CRC) patients. Notably, high expression of serum exosomal miR-203, a major form in circulation, was associated with distant metastasis and an independent poor prognostic factor, whereas low expression in tumor tissues was a poor prognostic factor in CRC patients. We also found that exosomes carrying miR-203 from CRC cells were incorporated into monocytes and miR-203 could promote the expression of M2 markers in vitro, suggesting miR-203 promoted the differentiation of monocytes to M2-tumor-associated macrophages (TAMs). In a xenograft mouse model, miR-203-transfected CRC cells developed more liver metastasis compared to control cells. In conclusion, serum exosomal miR-203 expression is a novel biomarker for predicting metastasis, possibly via promoting the differentiation of monocytes to M2-TAMs in CRC. Furthermore, we propose the concept of site-dependent functions for miR-203 in tumor progression.

15.
Ann Nutr Metab ; 71(3-4): 145-149, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28881342

RESUMO

BACKGROUND: The measurement of a single abdominal image on computed tomography (CT) can provide an estimate of the total body skeletal muscle. We evaluate the change of the area of the psoas major muscle (PMMA) in a CT which was performed routinely after gastrectomy in gastric cancer. METHODS: A total of 119 gastric cancer patients who underwent gastrectomy were enrolled for the study. A CT image at the top of the iliac crest level was obtained at the following times: 3 postoperative months (POM), 6 POM, 1 postoperative year (POY), 2 POY, 3 POY, and 5 POY. We analyzed the change rate of PMMA after gastrectomy and before or after recurrence. RESULTS: PMMA change after gastrectomy was approximately between -8 and -10% over the 5-year observation period. PMMA in the R2 (macroscopic residual tumor)/recurrence group was lower than that in the no recurrence group, and a significant difference was observed at 2 POY (-21.7 ± 3.6% vs. -7.9 ± 2.3%, p < 0.01). PMMA after freshly diagnosed recurrence had decreased significantly by 14.1 ± 1.8% (p < 0.01). CONCLUSIONS: Evaluation of PMMA change by CT after gastrectomy could assist in the diagnosis of the progression of cancer state in gastric cancer patients.

16.
J Thorac Dis ; 9(8): 2419-2426, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28932547

RESUMO

BACKGROUND: Cancer relapse is caused by residual isolated tumor cells (ITCs) remaining in the body after surgery. It is speculated that surgical manipulation may cause circulating tumor cells (CTCs) which are the origin of ITCs in the body. The occurrence of CTCs in surgical patients with non-small cell lung cancer (NSCLC) has been shown in retrospective observation, but not prospectively, thus we conducted a multicenter prospective study regarding the occurrence of CTCs by surgical manipulation. METHODS: Patients with T1b-2N0M0 lung cancer were studied. Blood samples were collected from the peripheral artery in the operating room at both pre- and post-lobectomy to extract CTCs by a size selection method. The CTCs detection rate, pathological findings, and background of each patient were studied. RESULTS: The histological diagnosis of 29 patients were adenocarcinoma in 24 patients, squamous cell carcinoma in 3 patients, and other types in 2 patients. The number of pre-CTCs positive patients was 13 and the number of post CTCs positive patients was 17. Among the 16 patients who were pre-CTCs negative, 4 patients showed post CTCs positive, while all pre-CTCs positive patients remained post-CTCs positive. CONCLUSIONS: The likelihood of CTC dislodgement by surgical manipulation is indicated based on the result that CTCs were detected after lung cancer surgery, where there were no cases of pre-CTCs positive and post CTCs negative.

18.
Oncology ; 92(6): 360-370, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28376502

RESUMO

OBJECTIVE: We clarified the predictive and prognostic value of circulating plasma exosomal microRNA-21 (miR-21) in each TNM stage of colorectal cancer (CRC) patients. METHODS: The microRNA (miRNA) profiles of the plasma exosomes, primary tumor tissues, and liver metastasis tissues from the same CRC patients were examined using a microarray. For validation analysis, the plasma exosome samples from 326 CRC patients were measured by TaqMan miRNA assays. RESULTS: In the miRNA microarray analyses, miR-21 showed the highest upregulation in exosomes, primary tumor tissues, and liver metastasis tissues. Significant correlations were demonstrated between exosomal miR-21 and tissue miR-21 levels. As for the relationship to the pathological condition, exosomal miR-21 showed a significant association with liver metastasis and TNM stage. The overall survival (OS) rates and disease-free survival (DFS) rates in high-exosomal-miR-21 patients were significantly worse than those in low-miR-21 patients. Exosomal miR-21 levels were an independent prognostic factor for OS and DFS in CRC patients with TNM stage II or III, and for OS in patients with TNM stage IV. CONCLUSION: Plasma exosomal miR-21 levels are a useful biomarker for the prediction of recurrence and poor prognosis in CRC patients with TNM stage II, III, or IV.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , MicroRNAs/sangue , MicroRNAs/genética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Análise em Microsséries , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/genética , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas
19.
Ann Thorac Surg ; 103(5): e469-e471, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28431731

RESUMO

Pulmonary artery reconstruction in lung cancer surgery is an effective surgical method to avoid pneumonectomy that leads to longer survival times with few adverse effects. The pericardium is often used for the interposition of a prosthetic conduit. A pericardial conduit can be easily and precisely constructed by surgical stapling, which facilitates pulmonary artery reconstruction. In this report, the process and pitfalls of surgical stapling are described.


Assuntos
Neoplasias Pulmonares/cirurgia , Pericárdio/transplante , Pneumonectomia/métodos , Artéria Pulmonar/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Grampeamento Cirúrgico , Humanos , Invasividade Neoplásica , Grampeamento Cirúrgico/efeitos adversos , Transplantes
20.
Oncol Lett ; 13(3): 1256-1263, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28454243

RESUMO

Predictive biomarkers for the recurrence of non-small cell lung cancer (NSCLC) in patients who have received curative resection are important for cancer treatment. The functional microRNAs (miRNAs/miRs) in the exosomes of plasma and serum samples are of interest as stable and non-invasive biomarkers for recurrence in cancer patients. The aim of the present study was to clarify the usefulness of plasma exosomal miRNAs as biomarkers for the prediction of recurrence in NSCLC following curative resection. First, microarray-based expression profiling of miRNAs derived from exosomes in the plasma of 6 patients was employed to identify a biomarker that distinguishes between patients with and without NSCLC recurrence. In the miRNA microarray analyses, the exosomal miR-21 and miR-4257 levels of the NSCLC patients showed marked upregulation in those individuals with recurrence compared with those without recurrence and healthy individuals. These two miRNAs were thus selected as recurrence-specific biomarkers and their potential was evaluated in a separate cohort of 195 NSCLC patients. In comparison to the levels in 30 healthy individuals, exosomal miR-21 and miR-4257 levels showed a significant increase in the NSCLC patients (P<0.01). When evaluating the clinicopathological significance of these miRNAs, exosomal miR-21 showed a significant association with tumor size and tumor-node-metastasis (TNM) stage (P<0.05). Exosomal miR-4257 showed a significant association with histological type, lymphatic invasion and TNM stage (P<0.05). The disease-free survival (DFS) rates of high exosomal miR-21 patients were significantly worse than those of low exosomal miR-21 patients (P<0.05), and the DFS rates of patients with high exosomal miR-4257 levels were significantly worse than those with low exosomal miR-4257 levels (P<0.01). In the Cox multivariate analysis, plasma exosomal miR-21 and miR-4257 expression showed a significance association with DFS (P<0.05). These results suggest that plasma exosomal miR-21 and mir-4257 expression has potential as a predictive biomarker for recurrence in NSCLC patients who have received curative resection.

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