Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Esophagus ; 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34365578

RESUMO

BACKGROUND: In transmediastinal esophagectomy (TME) with equivalent lymphadenectomy to transthoracic procedure, an understanding of surgical anatomy in the deep mediastinum near the aortic arch or tracheal bifurcation is essential for the safe procedure. The present study aimed to evaluate the bronchial arteries (BAs) with preoperative 3D-CT in TME. METHODS: Seventy-nine patients with thoracic esophageal cancer undergoing TME were examined by preoperative 3D-CT to evaluate BA variations in the number, branching pattern, and mediastinal course. For the right BAs (RBAs) crossing the esophagus, the mediastinal courses in transcervical view were classified in relation to the esophagus and tracheobronchi and compared with surgical findings. RESULTS: A total of 107 RBAs (1.35/person) were confirmed on preoperative 3D-CT. Of these, 61 (57.0%) crossed the esophagus dorsally (type Ed), and the remaining 46 (43.0%) crossed the esophagus ventrally (type Ev). During the left transcervical procedure, all type Ed RBAs were identified and mostly preserved (57/61, 93.4%) whereas most type Ev RBAs were identified (39/46, 84.8%), but more than half were sacrificed (26/46, 56.5%) for lymphadenectomy. The blood loss during the transcervical procedure was 17.0 ± 55.8 ml. The total number of dissected mediastinal lymph nodes was 23.7 ± 9.3. There were no significant complications related to extensive lymphadenectomy. CONCLUSIONS: Preoperative 3D-CT evaluation is useful to understand the mediastinal courses of BAs specific to the transcervical approach, which may allow BAs to be handled more carefully according to the type during surgery, contributing to a safer procedure in the deep mediastinum.

2.
Photodiagnosis Photodyn Ther ; 35: 102420, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34242818

RESUMO

BACKGROUND: Accurate diagnosis of peritoneal metastasis in gastric cancer (GC) is important to determine the appropriate treatment. This study aimed to examine whether matrix metalloprotease-14 (MMP-14) was a candidate enzyme in fluorescence imaging for the diagnosis of peritoneal metastasis in GC. METHODS: GC and normal peritoneal (NP) tissues from 96 and 20 patients, respectively were evaluated for MMP-14 expression. Live cell imaging of GC cell lines (NUGC4, MKN45, MKN74, HGC-27, and Kato-III) was performed using the MMP-14-activatable fluorescence probe; BODIPY-MMP. Furthermore, the overall survival (OS) was calculated in all patients (n = 96). RESULTS: MMP-14 expression was significantly higher in GC tissues (median: 3.57 ng/mg protein; range:0.64-24.4 ng/mg protein) than in NP tissues (median: 1.34 ng/mg protein; median: 0.53-3.09 ng/mg protein) (P < 0.01). Receiver operating characteristic curves showed that the area under the curve, sensitivity, and specificity were 0.907, 84.4%, and 90.0%, respectively. In live cell imaging using the BODIPY-MMP, fluorescence was observed in five GC cell lines. In the analysis of OS, the high expression of the MMP-14 group had a significantly poorer OS rate than the low expression of the MMP-14 group (P = 0.02). In the multivariate analyses, MMP-14 expression was an independent risk factor for OS (hazard ratio: 2.33; 95 % confidence interval: 1.05-5.45; P = 0.04). CONCLUSION: MMP-14 is a promising enzyme in intraoperative fluorescence imaging for peritoneal metastasis in GC, especially in patients with poor prognosis.


Assuntos
Neoplasias Peritoneais , Fotoquimioterapia , Neoplasias Gástricas , Biomarcadores Tumorais , Humanos , Metaloproteinase 14 da Matriz , Neoplasias Peritoneais/diagnóstico por imagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Prognóstico , Neoplasias Gástricas/diagnóstico por imagem
3.
Gastric Cancer ; 24(6): 1278-1292, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34251542

RESUMO

BACKGROUND: The Na+/K+-ATPase alpha1 subunit (ATP1A1) is a critical component of Na+/K+-ATPase (NKA), a membrane pump that maintains a low intracellular Na+/K+ ratio and retains cellular volume and osmolarity. ATP1A1 was recently implicated in tumor behavior. Therefore, the present study investigated the role of ATP1A1 in patients with gastric cancer (GC). METHODS: Knockdown experiments were conducted on human GC cell lines using ATP1A1 siRNA, and its effects on proliferation, the cell cycle, apoptosis, and cellular movement were examined. Gene expression profiling was performed by a microarray analysis. Primary tumor samples from 192 GC patients who underwent gastrectomy were subjected to an immunohistochemical analysis. RESULTS: High ATP1A1 expression levels were observed in NUGC4 and MKN74 cells. Cell proliferation was suppressed and apoptosis was induced by the siRNA-induced knockdown of ATP1A1. The microarray analysis showed that knockdown of ATP1A1 leads to the up-regulated expression of genes involved in the interferon (IFN) signaling pathway, such as STAT1, STAT2, IRF1, and IRF9. Furthermore, the depletion of ATP1A1 altered the phosphorylation of the MAPK pathway. The immunohistochemical analysis revealed that the expression of ATP1A1 was associated with the histological type, venous invasion, and the pathological T stage. Furthermore, the prognostic analysis showed a relationship between high ATP1A1 expression levels and poor postoperative survival. CONCLUSIONS: ATP1A1 appears to regulate tumor progression by altering IFN signaling, and high ATP1A1 expression levels were associated with poor postoperative survival in GC patients. The present results provide novel insights into the function of ATP1A1 as a mediator and/or biomarker of GC.

4.
Sci Rep ; 11(1): 10664, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34021168

RESUMO

Diagnosis of peritoneal metastasis in gastric cancer (GC) is essential for determining appropriate therapeutic strategies and avoiding non-essential laparotomy or gastrectomy. Recently, a variety of activatable fluorescence probes that can detect enzyme activities have been developed for cancer imaging. The aim of this study was to identify the key enzyme involved in peritoneal metastasis in GC. The enzymatic activity of gamma-glutamyl transpeptidase, dipeptidyl peptidase IV, and ß-galactosidase (ß-Gal) was assessed in lysates prepared from preserved human GC (n = 89) and normal peritoneal (NP; n = 20) samples. ß-Gal activity was significantly higher in the human GC samples than in NP samples, whereas no differences were observed in the activities of the other enzymes. Therefore, we used SPiDER-ßGal, a fluorescent probe that can be activated by ß-Gal, for imaging GC cell lines, peritoneal metastasis in a mouse model, and fresh human resected GC samples (n = 13). All cell lines showed fluorescence after applying SPiDER-ßGal, and metastatic nodules in the mice gradually developed high fluorescence that could be visualized with SPiDER-ßGal. The human GC samples showed significantly higher fluorescence than NP samples. ß-Gal is a useful target enzyme for fluorescence imaging of peritoneal metastasis in GC.

5.
Esophagus ; 18(3): 461-467, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33599862

RESUMO

BACKGROUND: The aim of the present study was to evaluate subcarinal lymph node dissection in transmediastinal radical esophagectomy and subcarinal lymph node metastasis in patients with esophageal cancer. METHODS: Three hundred and twenty-three patients with primary esophageal cancer who underwent transmediastinal or transthoracic esophagectomy with radical two- or three-field lymph node dissection were retrospectively investigated. The clinicopathological characteristics of patients with subcarinal lymph node metastasis were analyzed in detail. RESULTS: The median of dissected subcarinal lymph nodes in transmediastinal and transthoracic esophagectomy groups was 6 and 7, respectively, and there was no significant difference between the two groups (p = 0.12). Of all patients, 26 (8.0%) were pathologically diagnosed as positive for subcarinal lymph node metastasis, whereas only 7 (26.9%) of those with metastasis were preoperatively diagnosed as positive. In addition, all patients with subcarinal lymph node metastasis had other non-subcarinal lymph node metastasis. By univariate analysis, subcarinal lymph node metastasis was found in larger (≥ 30 mm) and deeper (T3/T4a) primary lesions (p = 0.02 and 0.02, respectively), but it was not found in 49 patients with the primary lesion located in the upper thoracic esophagus. CONCLUSIONS: Subcarinal lymph nodes can be dissected in transmediastinal esophagectomy, almost equivalent to transthoracic esophagectomy. The tumor size, depth, and location may be predictive factors for subcarinal lymph node metastasis.

6.
Surg Today ; 51(3): 422-431, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32772168

RESUMO

PURPOSE: The long-term prognostic impact of the hemoglobin A1c levels has not yet been evaluated in patients with gastric cancer. The present study investigated the clinical significance of the hemoglobin A1c levels in patients with gastric cancer. METHODS: We enrolled 294 patients with stage II, III, or IV gastric cancer who underwent gastrectomy. The patients were divided into high preoperative hemoglobin A1c (> 6.0%) and low preoperative hemoglobin A1c (≤ 6.0%) groups. RESULTS: In patients with stage III gastric cancer with severe postoperative complications, the high preoperative hemoglobin A1c group had a significantly worse prognosis than the low preoperative hemoglobin A1c group (p = 0.0409). In patients without severe postoperative complications, the high preoperative hemoglobin A1c group had a significantly favorable prognosis compared with the low preoperative hemoglobin A1c group (p = 0.0348). CONCLUSION: The prognosis of patients with stage III gastric cancer having high preoperative hemoglobin A1c levels greatly depended on the presence or absence of postoperative complications. To avoid postoperative complications, optimal perioperative management and personalized treatments are critical, particularly for these patients.


Assuntos
Gastrectomia/efeitos adversos , Hemoglobina A Glicada/metabolismo , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Assistência Perioperatória , Complicações Pós-Operatórias/prevenção & controle , Período Pré-Operatório , Prognóstico , Neoplasias Gástricas/patologia
7.
Anticancer Res ; 40(6): 3163-3167, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487611

RESUMO

BACKGROUND/AIM: Ultrasonically activated surgical devices (USADs) have become indispensable instruments for gastrointestinal surgery. In this study, we investigated the oncological safety of the use of USADs. MATERIALS AND METHODS: We harvested and cultivated the splashes and mist scattered from an USAD when cutting MKN45-derived cancer nodules. Seven days later, we observed viable cancer cells and the total number of cells was counted. The histopathology of the nodules cut by the USAD was also examined. RESULTS: The existence of viable cancer cells was confirmed by ex vivo cell culture. The number of viable cancer cells was reduced by slow grasping of the USAD. The surface of cancerous tissue cut by the USAD was partially heat-denatured, however, there were some parts in which cancerous tissue was exposed on the surface. CONCLUSION: Surgeons should recognize the possibility that cancer cells may be scattered by USAD use.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Terapia por Ultrassom/métodos , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Nus , Neoplasias Gástricas/patologia
9.
Gastric Cancer ; 22(6): 1247-1255, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30888536

RESUMO

BACKGROUND: Pylorus-preserving gastrectomy is an alternative to distal gastrectomy for early gastric cancer, and is expected to have postoperative advantages including maintenance of body weight. Overweight/obesity is a risk factor for chronic disorders, including hypertension and diabetes mellitus; in these conditions, body weight control is frequently required as part of treatment. It remains unknown whether pylorus-preserving gastrectomy should be performed in overweight/obese patients because excess body weight may be maintained postoperatively. METHODS: We retrospectively investigated body weight changes and postoperative nutritional status of overweight/obese patients who underwent laparoscopic distal gastrectomy (LDG) or laparoscopic pylorus-preserving gastrectomy (LPPG) between 2006 and 2015. Among 349 overweight patients (BMI ≥ 25 kg/m2), 101 LDG and 101 LPPG cases were compared after propensity score matching to adjust for patient characteristics. RESULTS: The mean relative body weight ratios (postoperative/preoperative ratios) were 87.5 ± 8.0% after LDG and 89.6 ± 6.7% after LPPG (difference not significant, p = 0.088). The prealbumin level at 2 years and hemoglobin levels at 6 months, 1 year and 2 years were significantly well maintained after LPPG than after LDG. Prealbumin and hemoglobin levels at 2 years had almost returned to baseline levels in the LPPG group. The superiority of LPPG in the hemoglobin level was confirmed regardless of reconstruction methods after LDG. CONCLUSIONS: For overweight/obese patients, LDG and LPPG resulted in similar degrees of postoperative weight loss, with patients achieving near-ideal body weight. The postoperative nutritional advantages of LPPG were confirmed. LPPG seemed to be better even for overweight/obese patients who meet indication criteria.


Assuntos
Gastrectomia/métodos , Obesidade/complicações , Sobrepeso/complicações , Neoplasias Gástricas/cirurgia , Idoso , Feminino , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Período Pós-Operatório , Piloro/cirurgia , Estudos Retrospectivos , Perda de Peso
10.
Carcinogenesis ; 39(2): 263-271, 2018 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-29228320

RESUMO

Zuotin-related factor 1 (ZRF1) is a recently characterized epigenetic factor involved in transcriptional regulation and is highly overexpressed in several malignancies, but it is not known whether it plays a role in gastric cancer (GC). In this study, we investigated whether ZRF1 acts as a cancer-promoting gene through its activation/overexpression in GC. We analyzed five GC cell lines and 133 primary tumors, which had been curatively resected in our hospital between 2001 and 2003. Overexpression of ZRF1 was detected in GC cell lines (four out of five lines, 80.0%) and was detected in primary tumor samples of GC (52 out of 133 cases, 39.1%) and significantly correlated with differentiated histological type, venous invasion, lymphatic invasion, advanced stage and a higher recurrence rate. ZRF1-overexpressing tumors had a worse survival rate than those with non-expressing tumors (P < 0.01, log-rank test). ZRF1 positivity was independently associated with a worse outcome in the multivariate analysis (P < 0.01; hazard ratio 4.92; 95% confidence interval: 1.6-21.1). In ZRF1-overexpressing GC cells, knockdown of ZRF1 using specific siRNAs inhibited the cell proliferation, migration and invasion and induced apoptosis in a p53-dependent manner. These findings suggest that ZRF1 plays a crucial role in tumor malignant potential through its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/análise , Proteínas de Ligação a DNA/metabolismo , Proteínas Oncogênicas/metabolismo , Neoplasias Gástricas/patologia , Adenocarcinoma/mortalidade , Adulto , Idoso , Linhagem Celular Tumoral , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares , Prognóstico , Modelos de Riscos Proporcionais , Proteínas de Ligação a RNA , Neoplasias Gástricas/mortalidade , Regulação para Cima
11.
Oncotarget ; 8(48): 84112-84122, 2017 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-29137409

RESUMO

Background: To detect a novel treatment target for adenocarcinoma of the esophagogastric junction (AEG), we tested whether C-terminal tensin-like (CTEN), a member of the tensin gene family and frequently overexpressed in various cancers, acts as a cancer-promoting gene through overexpression in AEG. Materials and Methods: We analyzed 5 gastric adenocarcinoma (GC) cell lines and 104 primary AEG tumors curatively resected in our hospital between 2000 and 2010. Results: CTEN overexpression was detected in GC cell lines (2/5 cell lines; 40%) and primary AEG tumor samples (35/104 cases; 34%). CTEN knockdown using several specific siRNAs inhibited the proliferation, migration, and invasion of CTEN-overexpressing cells. CTEN overexpression was significantly correlated with more aggressive venous and lymphatic invasion, deeper tumor depth, and higher rates of lymph node metastasis and recurrence. Patients with CTEN-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors (P < 0.0001, log-rank test) in an expression-dependent manner. CTEN positivity was independently associated with a worse outcome in the multivariate analysis (P = 0.0423, hazard ratio 3.54 [1.04-16.4]). Conclusions: CTEN plays a crucial role in tumor cell proliferation, migration, and invasion through its overexpression, which highlights its usefulness as a prognosticator and potential therapeutic target in AEG.

12.
World J Gastroenterol ; 23(31): 5650-5668, 2017 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-28883691

RESUMO

Hepatocellular carcinoma (HCC), with its high incidence and mortality rate, is one of the most common malignant tumors. Despite recent development of a diagnostic and treatment method, the prognosis of HCC remains poor. Therefore, to provide optimal treatment for each patient with HCC, more precise and effective biomarkers are urgently needed which could facilitate a more detailed individualized decision-making during HCC treatment, including the following; risk assessment, early cancer detection, prediction of treatment or prognostic outcome. In the blood of cancer patients, accumulating evidence about circulating tumor cells and cell-free nucleic acids has suggested their potent clinical utilities as novel biomarker. This concept, so-called "liquid biopsy" is widely known as an alternative approach to cancer tissue biopsy. This method might facilitate a more sensitive diagnosis and better decision-making by obtaining genetic and epigenetic aberrations that are closely associated with cancer initiation and progression. In this article, we review recent developments based on the available literature on both circulating tumor cells and cell-free nucleic acids in cancer patients, especially focusing on Hepatocellular carcinoma.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , DNA Tumoral Circulante/sangue , Neoplasias Hepáticas/diagnóstico , Células Neoplásicas Circulantes , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Tomada de Decisão Clínica/métodos , Progressão da Doença , Detecção Precoce de Câncer/métodos , Biópsia Líquida , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , MicroRNAs/sangue , Medicina de Precisão/métodos , Prognóstico , RNA Mensageiro/sangue
13.
Sci Rep ; 7(1): 5708, 2017 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-28720759

RESUMO

This study explored decreased tumor suppressor microRNA (miRNA) plasma levels in pancreatic cancer (PCa) patients to clarify their potential as novel biomarkers and therapeutic targets. We used the microRNA array-based approach to select candidates by comparing plasma levels between PCa patients and healthy volunteers. Six down-regulated miRNAs (miR-107, miR-126, miR-451, miR-145, miR-491-5p, and miR-146b-5p) were selected. Small- and large-scale analyses using samples from 100 PCa patients and 80 healthy volunteers revealed that miR-107 was the most down-regulated miRNA in PCa patients compared with healthy volunteers (P < 0.0001; area under the receiver-operating characteristic curve, 0.851). A low miR-107 plasma level was significantly associated with advanced T stage, N stage, and liver metastasis and was an independent factor predicting poor prognosis in PCa patients (P = 0.0424; hazard ratio, 2.95). miR-107 overexpression in PCa cells induced G1/S arrest with the production of p21 and inhibited cell proliferation through the transcriptional regulation of Notch2. In vivo, the restoration and maintenance of the miR-107 plasma level significantly inhibited tumor progression in mice. Depletion of the tumor suppressor miR-107 in plasma relates to tumor progression and poor outcomes. The restoration of the plasma miR-107 level might be a novel anticancer treatment strategy for PCa.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , MicroRNAs/sangue , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Idoso , Animais , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/secundário , Masculino , Camundongos SCID , MicroRNAs/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Transplante de Neoplasias , Neoplasias Pancreáticas/sangue , Prognóstico
14.
Anticancer Res ; 37(6): 3129-3135, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28551654

RESUMO

BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEG) has increased in Western and Eastern countries, and its prognosis remains poor. We tested whether epidermal growth factor receptor (EGFR), that is overexpressed in various tumors, acts as a cancer-promoting gene through overexpression in AEG. MATERIALS AND METHODS: We analyzed 104 primary AEG tumors which were curatively resected in our hospital between 2000 and 2010. RESULTS: Overexpression of EGFR protein was detected in 47% primary AEG tumor samples, and significantly associated with venous and lymphatic invasion, tumor depth and lymph node metastasis. The high-expression group had a significantly poorer prognosis than the low expression group for overall and disease-free survival. EGFR positivity was independently associated with a worse outcome in the multivariate analysis (p=0.0397, hazard ratio(HR)=2.048). CONCLUSION: EGFR plays a pivotal role in AEG through its overexpression, which highlights its usefulness as a prognosticator and potential therapeutic target in AEG.


Assuntos
Adenocarcinoma/química , Biomarcadores Tumorais/análise , Receptores ErbB/análise , Neoplasias Esofágicas/química , Junção Esofagogástrica/química , Neoplasias Gástricas/química , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Modelos de Riscos Proporcionais , Fatores de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
15.
Int J Clin Oncol ; 22(5): 897-904, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28488013

RESUMO

BACKGROUND: There is no evidence that monitoring tumor dynamics using sensitive tumor markers contributes to treatment decision-making and prognosis in gastric cancer patients with tumor recurrence. This study was designed to investigate the significance of tumor markers in monitoring peritoneal recurrence of gastric cancer. METHODS: We retrospectively analysed 102 consecutive patients who developed recurrence after curative gastrectomy for gastric cancer at our institute between 2002 and 2011. They were followed intensively using tumor markers such as carbohydrate antigen 19-9 and carcinoembryonic antigen. RESULTS: Of 102 patients who exhibited recurrence, 51 had peritoneal recurrence. These patients were divided into three groups according to the status of tumor markers at the time of recurrence. Each tumor marker was re-elevated in 28 patients (58%) (re-elevation group; REG), was continuously elevated since initial surgery in 13 patients (22%) (continuous elevation group; CEG) and was not elevated in 10 patients (20%) (non-elevation group; NEG). With regard to survival after recurrence and total postoperative survival, patients in the REG were significantly better than those in the other groups ( p = 0.001, p = 0.018, respectively). REG patients received more different types of chemotherapy regimens than NEG patients because of monitoring (p = 0.018). Multivariate analysis revealed that re-elevation of tumor markers at the time of recurrence was an independent and better prognostic factor for peritoneal recurrence (p = 0.003, hazard ratio 0.29). CONCLUSION: Monitoring of tumor dynamics with sensitive tumor markers may contribute to the decision-making process for more promising chemotherapeutic regimens by avoiding subsequent ileus and lead to better prognosis in gastric cancer patients with peritoneal recurrence.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Peritoneais/patologia , Neoplasias Gástricas/patologia , Idoso , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/cirurgia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Análise de Sobrevida
16.
Br J Cancer ; 116(2): 218-226, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-27898655

RESUMO

BACKGROUND: PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) is a serine-threonine kinase and overexpressed in various types of cancer by inhibiting the transactivation activities of p53 and PTEN. We tested whether PBK/TOPK acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). METHODS: We analysed five GC cell lines and 144 primary tumours, which were curatively resected in our hospital between 2001 and 2003. RESULTS: Overexpression of the PBK/TOPK protein was frequently detected in GC cell lines (4 out of 5 lines, 80.0%) was detected in primary tumour samples of GC (24 out of 144 cases, 16.6%) and was significantly correlated with venous invasion, tumour depth and recurrence rate. PDZ-binding kinase/T-LAK cell-originated protein kinase-overexpressing tumours had a worse survival rate than those with non-expressing tumours (P=0.0009, log-rank test). PDZ-binding kinase/T-LAK cell-originated protein kinase positivity was independently associated with a worse outcome in multivariate analysis (P<0.0001, hazard ratio 6.40 (2.71-14.49)). In PBK/TOPK-overexpressing GC cells, knockdown of PBK/TOPK inhibited the cell proliferation through the p53 activation in a TP53 mutation-dependent manner and inhibited the migration/invasion through the PTEN upregulation in a TP53 mutation-independent manner. CONCLUSIONS: These findings suggest PBK/TOPK plays a crucial role in tumour malignant potential through its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.


Assuntos
Biomarcadores Tumorais/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Regulação para Cima/genética
17.
Oncotarget ; 8(63): 106538-106550, 2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-29290969

RESUMO

Background: Several studies have identified the decreased expression of the tumor suppressor miR-101 in various cancers. In this study, we tested miR-101 as a potential therapeutic target and novel plasma biomarker for gastric cancer (GC). Results: The miR-101 expression level was significantly lower in GC tissues (P = 0.0038) and GC cell lines (P = 0.0238) than in normal gastric mucosa. Both exosomal and plasma miR-101 were significantly downregulated in GC patients compared with healthy volunteers (P = 0.0281 and P < 0.0001, respectively). Low miR-101 plasma level was significantly associated with advanced T factor, advanced disease stage, and peritoneal metastasis and predicted poor prognosis in GC patients (P = 0.0368; hazard ratio, 3.079; 95% confidence interval: 1.06-11.08). Overexpression of miR-101 in GC cells induced apoptosis by inhibiting MCL1 and suppressed cell migration and invasion by regulating ZEB1. Conclusions: Depletion of the tumor suppressor miRNA-101 in plasma is related to tumor progression and poor outcomes. Low plasma miR-101 may be a biomarker for GC, and its restoration might be a novel anticancer treatment strategy.

18.
Am J Cancer Res ; 6(11): 2729-2736, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27904785

RESUMO

Several studies have demonstrated that YWHAZ (14-3-3ζ), included in the 14-3-3 family of proteins, is implicated in the initiation and progression of cancers. To detect a novel treatment target for adenocarcinoma of the esophagogastric junction (AEG), we tested whether YWHAZ acted as a cancer-promoting gene through its overexpression in AEG. We analyzed YWHAZ protein expression in 92 consecutive primary AEG tumors, which had been curatively resected in our institution between 2000 and 2010. Overexpression of the YWHAZ protein was frequently detected in primary AEG tumor samples (46% (42/92)). Overexpression of YWHAZ was significantly correlated with Siewert type III tumor, larger tumor size (≥40 mm) and higher rates of lymph node metastasis and recurrence. Patients with YWHAZ-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors (P = 0.011, log-rank test) in an intensity expression-dependent manner. Patients with YWHAZ-overexpression tumors had worse overall survival rates than those with lower-expression tumors. YWHAZ positivity was independently associated with a worse outcome in the multivariate analysis (P = 0.0015, hazard ratio 4.49 [1.736-13.06]). In conclusion, YWHAZ plays a crucial role in poor outcomes of patients with AEG through its overexpression, which highlights its usefulness as a prognosticator and potential therapeutic target and indicator in AEG.

19.
Anticancer Res ; 36(12): 6457-6466, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27919968

RESUMO

BACKGROUND: PDZ-binding kinase/T-cell-originated protein kinase (PBK/TOPK) is a serine-threonine kinase and overexpressed in various types of cancer. PBK/TOPK is associated with tumor cell development and progression through suppression of p53 function. In this study, we tested whether PBK acts as a cancer-promoting factor by being overexpressed in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: We analyzed PBK/TOPK expression in 15 ESCC cell lines, and 54 primary ESCC tumors that were curatively resected between 1994 and 2007. RESULTS: Overexpression of the PBK/TOPK protein was detected in 93% (14/15) ESCC cell lines and 19% (10/54) primary ESCC tumor samples, and significantly correlated with macroscopic appearance and tumor depth. PBK/TOPK positivity was independently associated with worse outcome in multivariate analysis (p=0.0235, hazard ratio=3.58). Knockdown of PBK/TOPK using specific siRNAs inhibited the cell proliferation, invasion/migration of PBK/TOPK-overexpressing ESCC cell lines. CONCLUSION: These findings suggest that PBK/TOPK plays a crucial role in tumor malignant potential through its overexpression in ESCC.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Carcinoma de Células Escamosas/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade
20.
Int J Mol Sci ; 17(9)2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27598137

RESUMO

MicroRNAs (miRNAs) are short noncoding RNAs that post-transcriptionally regulate gene expression and play important roles in various physiological and developmental processes such as oncogenic or tumor suppressive regulators. Specific miRNA expression signatures have been identified in a number of human cancers. Cell-free miRNAs have recently been stably detected in plasma and serum (circulating miRNAs), and their presence in blood has attracted the attention of researchers due to their potential as non-invasive biomarkers. Circulating miRNAs have emerged as tumor-associated biomarkers that reflect not only the existence of early-stage tumors, but also the dynamics and status of advanced stage tumors, tumor recurrence, and drug sensitivities. This methodology for liquid biopsy may provide non-invasive and reproductive biomarkers and individualized therapeutic strategies for cancer patients. We herein review the current phase of biological and clinical research on the circulating miRNAs of solid cancers, particularly digestive tract cancers, and discuss future perspectives. The present review may be beneficial for future research on miRNAs used to detect various cancers.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Gastrointestinais/sangue , MicroRNAs/sangue , Resistencia a Medicamentos Antineoplásicos , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...