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1.
Anticancer Res ; 41(4): 2117-2122, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813422

RESUMO

BACKGROUND/AIM: Stanniocalcin2 (STC2) is associated with proliferation, invasion, and metastasis in various cancers. We examined the clinical significance of STC2 mRNA expression in patients with colorectal cancer (CRC). PATIENTS AND METHODS: Relative expression levels of STC2 mRNA in CRC tissues and corresponding normal mucosa obtained from 202 patients were measured using quantitative real-time reverse transcriptase-polymerase chain reaction. RESULTS: Expression of STC2 mRNA was higher in the cancer tissue than in the adjacent normal mucosa. STC2 mRNA expression in cancer tissues was associated with tumour size, liver metastasis, venous invasion, and lymph node metastasis. High expression of STC2 mRNA was significantly associated with poorer postoperative survival (p=0.0003). Multivariate analysis showed that high expression of STC2 mRNA was an independent predictor of postoperative survival. CONCLUSION: High expression of STC2 mRNA in CRC tissue may be a useful prognostic marker in patients with CRC.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Glicoproteínas/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Feminino , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sobrevida , Resultado do Tratamento
2.
Gan To Kagaku Ryoho ; 46(10): 1653-1655, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31631165

RESUMO

A 64-year-old woman was diagnosed with hereditary spherocytosis 30 years ago and underwent splenectomy. She presented to the hospital with lower abdominal pain and was diagnosed with sigmoid colon cancer(cT3N3M1[LYM], H1, Stage Ⅳ)for which sigmoidectomy was performed. On the 7th postoperative day, a fever of 40℃ and an inflammatory reaction were observed. She developed a consciousness disorder the next day, and her condition rapidly deteriorated along with the development of septic shock and disseminated intravascular coagulation(DIC). With the aid of a ventilator, immediate treatment for DIC was started, but reversion of septic shock and DIC was not possible, and the patient died of multiple organ dysfunction on the 17th postoperative day. Computed tomography and urinalysis performed during the course of treatment showed no infected lesion, but Citrobacter spp. was detected thrice in venous blood culture. Hence, the patient was diagnosed as a case of Citrobacter overwhelming post splenectomy infection(OPSI). To our knowledge, this is the first report of Citrobacter spp. infection following an abrupt course of OPSI.


Assuntos
Coagulação Intravascular Disseminada , Neoplasias do Colo Sigmoide , Esplenectomia , Feminino , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Neoplasias do Colo Sigmoide/cirurgia
3.
Gan To Kagaku Ryoho ; 45(1): 145-147, 2018 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-29362336

RESUMO

A patient was 60-year-old man. In March 2011, the small bowel tumor with perforation was found and the partial resection of small intestine was urgently performed. KIT of resected specimen was positive. Then, diagnosis as GIST was defined. Oral administration of imatinib was started, but it was finished in 5 months because of development of the systemic edema. In February 2013, the abdominal CT revealed a tumor of 20 cm in size in the pelvis. Upon laparotomy, we detected the GIST recurrence generated at the region of small intestine anastomosis where manipulated previously, then resected all of tumor and partially small intestine. Afterward, we diagnosed as a recurrence of GIST. In March 2014, the abdominal CT found 4 cm sized mesenteric tumor and 2 cm sized abdominal wall tumor. The laparotomy was performed and we found 5 disseminated nodules intraperitoneally. We confirmed that all of these disseminated nodules were successfully removed. We defined them as re-recurrence of GIST. Six years and 5 months have elapsed since the first operation was performed, but there is no sign of three times recurrence.


Assuntos
Tumores do Estroma Gastrointestinal/cirurgia , Neoplasias Intestinais/cirurgia , Perfuração Intestinal/cirurgia , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Mesilato de Imatinib/uso terapêutico , Neoplasias Intestinais/complicações , Neoplasias Intestinais/tratamento farmacológico , Perfuração Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Fatores de Tempo
4.
Gan To Kagaku Ryoho ; 44(12): 1317-1319, 2017 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-29394619

RESUMO

We report the case of a 79-year-old woman with repeated abdominal wall recurrence of gallbladder cancer. The original diagnosis was gallbladder carcinoma. She underwent open liver bed dissection and lymph node dissection. Postoperative pathological examination indicated T2N1M0, Stage III disease. She received 6 courses of postoperative chemotherapy with gemcitabine. Two years and 2 months after the surgery, we detected a 13 mm mass under the abdominal wall scar on CT, and we resected this tumor. Pathological findings indicated adenocarcinoma, which was found to be metastasis of the gallbladder cancer. She was treated with S-1 for 8 courses postoperatively. However, 3 years 4 months after the first surgery, a tumor of 22mm was detected in the abdominal wall on the caudal side away from the previous tumor excision site. We resected the abdominal wall including the tumor. The pathological examination revealed adenocarcinoma, which was again metastasis from gallbladder cancer. The increase of CA19-9 was confirmed around 4 years and 7months after the first operation. An abdominal wall tumor of 45mm was detected in contact with the iliac bone near the last excision site and it proved to be a recurrence of gallbladder carcinoma. We performed abdominal wall tumor resection, again identifying adenocarcinoma, which was the third recurrence of gallbladder cancer. Despite continued abdominal wall recurrence, she is alive and well without metastasis for more than 5 years.


Assuntos
Neoplasias Abdominais/cirurgia , Parede Abdominal/cirurgia , Adenocarcinoma/cirurgia , Neoplasias da Vesícula Biliar/patologia , Neoplasias Abdominais/patologia , Neoplasias Abdominais/secundário , Parede Abdominal/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Recidiva , Fatores de Tempo
5.
Biochem Biophys Res Commun ; 479(3): 447-452, 2016 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-27641663

RESUMO

Our previous study showed that enhanced carbonyl stress is closely related to schizophrenia. The endogenous secretory receptor for advanced glycation end-products (esRAGE) is a splice variant of the AGER gene and is one of the soluble forms of RAGE. esRAGE is considered to be a key molecule for alleviating the burden of carbonyl stress by entrapping advanced glycation end-products (AGEs). In the current study, we conducted genetic association analyses focusing on AGER, in which we compared 212 schizophrenic patients to 214 control subjects. We also compared esRAGE levels among a subgroup of 104 patients and 89 controls and further carried out measurements of total circulating soluble RAGE (sRAGE) in 25 patients and 49 healthy subjects. Although the genetic association study yielded inconclusive results, multiple regression analysis indicated that a specific haplotype composed of rs17846798, rs2071288, and a 63 bp deletion, which were in perfect linkage disequilibrium (r2 = 1), and rs2070600 (Gly82Ser) were significantly associated with a marked decrease in serum esRAGE levels. Furthermore, compared to healthy subjects, schizophrenia showed significantly lower esRAGE (p = 0.007) and sRAGE (p = 0.03) levels, respectively. This is the first study to show that serum esRAGE levels are regulated by a newly identified specific haplotype in AGER and that a subpopulation of schizophrenic patients are more vulnerable to carbonyl stress.


Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Receptor para Produtos Finais de Glicação Avançada/sangue , Esquizofrenia/sangue , Adulto , Estudos de Casos e Controles , Feminino , Deleção de Genes , Marcadores Genéticos , Predisposição Genética para Doença , Genótipo , Produtos Finais de Glicação Avançada/sangue , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Carbonilação Proteica , Receptor para Produtos Finais de Glicação Avançada/genética , Análise de Regressão , Esquizofrenia/genética
6.
Gan To Kagaku Ryoho ; 43(12): 1908-1910, 2016 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-28133172

RESUMO

A 75-year-old man admitted for left lateral abdominal pain was found to have advanced poorly differentiated gastric adenocarcinoma with abdominal para-aortic and Virchow's lymph node metastases, which was diagnosed to be clinical Stage IV (T3N3H0M1[LYM]). As curative surgery was not deemed possible, we started chemotherapy administration using S-1 (120mg/day)administered orally for 3 weeks and cisplatin(CDDP 100mg/body)administered intravenously on day 8. After 6 courses of chemotherapy, a CT scan showed that all lymph nodes metastases had disappeared, resulting in downstaging to clinical Stage II (T3[SE]N0H0P0M0). Thus, we performed total gastrectomy, lymph node dissection(D2), and splenectomy. Histological findings showed no residual tumor cells in any of the lymph nodes. However, cancer cells remained in the primary gastric lesion. The pathological response to chemotherapy was judged to be Grade 2. The patient has been recurrence-free for 5 years after surgery.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia de Salvação , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/cirurgia , Idoso , Cisplatino/administração & dosagem , Combinação de Medicamentos , Humanos , Masculino , Terapia Neoadjuvante , Ácido Oxônico/administração & dosagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem
7.
Gan To Kagaku Ryoho ; 42(10): 1268-70, 2015 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-26489568

RESUMO

We report 2 cases of signet ring cell carcinoma of the appendix and colon. Case 1: A 61-year-old man was admitted for lower abdominal pain. Colonoscopy revealed an elevated lesion in the orifice of the appendix. Signet ring cell carcinoma was diagnosed on biopsy. The surgical findings showed multiple peritoneal dissemination nodules, while the primary tumor was unresectable owing to extensive invasion into the retroperitoneum. The histopathological findings were signet ring cell carcinoma, T4b (retroperitoneum), NX, P3, Stage Ⅳ. Although the patient received 14 courses of treatment with S-1 as postoperative chemotherapy, he died of his illness at 32 postoperative months. Case 2: A 76-year-old man was admitted for abdominal pain. Perforation of the lower gastrointestinal tract was diagnosed on abdominal CT, and an emergency operation was performed. The surgical findings demonstrated a large number of peritoneal dissemination nodules, cecal invasion of a sigmoid tumor, and perforation of the ascending colon. The primary tumor was thought to be unresectable, and the perforated segment was resected. The histopathological findings were signet ring cell carcinoma, T4b (cecum), NX, P3, Stage Ⅳ. Although 11 courses of treatment using FOLFIRI+Bev were administered as postoperative chemotherapy, the patient died of his illness at 26 postoperative months.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apêndice/patologia , Carcinoma de Células em Anel de Sinete/tratamento farmacológico , Neoplasias Peritoneais/secundário , Neoplasias do Colo Sigmoide/tratamento farmacológico , Neoplasias do Colo Sigmoide/patologia , Idoso , Carcinoma de Células em Anel de Sinete/cirurgia , Terapia Combinada , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias do Colo Sigmoide/cirurgia
8.
Gan To Kagaku Ryoho ; 42(10): 1289-91, 2015 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-26489575

RESUMO

In March 2011, trastuzumab was approved for treating human epidermal growth factor receptor 2 (HER2) positive advanced gastric cancer (AGC) in Japan. Therefore, all patients with AGC should be evaluated for HER2 status. In this study, we analyzed the clinicopathological features and current status of treatment in HER2 positive gastric cancer. One hundred 6 gastric cancer patients were examined for HER2 expression in our hospital between March 2011 and August 2014. Sixteen patients (15.1%) were HER2 positive. There was no correlation between HER2 status and age, sex, and location of tumor; however, HER2 positivity was significantly more frequent in patients with intestinal type tumors and had a tendency towards being more frequent in patients with macroscopic types 0, 1 or 2. Trastuzumab was administered to 10 patients with HER2 positive AGC. The total number of doses of trastuzumab was 1 to 44 (median 7.5), and the therapeutic effect of trastuzumab combination chemotherapy was 1 patient with a complete response and 4 with a partial response. Adverse events due to trastuzumab were not observed. The incidence of HER2 over-expression was 15.1%, and trastuzumab combination chemotherapy was relatively safe and effective.


Assuntos
Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Receptor ErbB-2/análise , Neoplasias Gástricas/química , Resultado do Tratamento
9.
Gan To Kagaku Ryoho ; 42(12): 2142-4, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26805291

RESUMO

AIM: To evaluate short-term outcomes of laparoscopy-assisted colectomy (LAC) in elderly patients with colorectal carcinoma. METHODS: A total of 289 colorectal cancer patients underwent LAC between 2008 and 2013. They were divided into an elderly group (<80 years of age, group E), and a younger group (<80 years of age, group Y). The treatment results, including the surgery-related factors, the perioperative course, and the pre- and postoperative complications, were retrospectively analyzed. RESULTS: There were 49 patients in group E, and 240 patients in group Y. There was no significant difference between the 2 groups considering the operative time, blood loss, rate of transfusion, post-operative hospital stay, rate of conversion to open surgery, or rate of complications, except for the number of patients with an ASA classification of greater than Grade 2 and the degree of lymph node dissection. CONCLUSIONS: LAC in elderly patients was found to be relatively safe because it was associated with a reduction in damage to the abdominal wall, and with an early recovery from surgery. These results suggest that the indications of LAC could be expanded for elderly patients.


Assuntos
Neoplasias Colorretais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Colectomia/métodos , Neoplasias Colorretais/patologia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento
10.
Biochem J ; 463(1): 75-82, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24995813

RESUMO

Clarification of the roles of PAMPs (pathogen-associated molecular patterns) and DAMPs (damage-associated molecular patterns) is indispensable for therapeutic strategies against various inflammatory diseases. RAGE (receptor for advanced glycation end-products) is one of the PRRs (pattern recognition receptors) and has been implicated in autoimmune and inflammatory diseases. Effective remedies targeting RAGE are required for the diseases. In the present study, we show that cAMP-induced modulation of the RAGE isoform in macrophages can control the inflammatory state in both in vitro and in vivo experimental conditions. The RAGE ligand S100B stimulated MCP-1 (monocyte chemoattractant protein-1) secretion from peritoneal macrophages, but cAMP elevation suppressed it by converting the RAGE isoform from a membrane-bound into a soluble form. This shedding is the result of ectodomain cleavage of mRAGE (membrane-bound RAGE) by MMP9 (matrix metalloproteinase 9). Furthermore, forskolin significantly inhibited peritoneal macrophage accumulation in a mouse S100B-induced peritonitis model. These results suggest that cAMP serves as a negative regulator of ligand-RAGE signalling and macrophage recruitment by mRAGE down-regulation and formation of decoys as soluble receptors. The present study should deepen our understanding of the pathogenesis of RAGE-mediated tissue derangement and provide new clues for overcoming RAGE-related inflammatory diseases.


Assuntos
AMP Cíclico/metabolismo , Macrófagos Peritoneais/metabolismo , Receptores Imunológicos/metabolismo , Transdução de Sinais , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , AMP Cíclico/genética , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Macrófagos Peritoneais/patologia , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Knockout , Estrutura Terciária de Proteína , Proteólise , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/genética , Subunidade beta da Proteína Ligante de Cálcio S100/genética , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo
11.
Gan To Kagaku Ryoho ; 41(12): 2232-4, 2014 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-25731480

RESUMO

We investigated the significance of staging laparoscopy (SL) for clinical Stage III/IVgastric cancer.SL was performed in 60 patients with clinical Stages III/IV gastric cancer.Pre -SL Stages were T3/4a/4b in 3/49/8 patients, N1/2/3 in 14/21/25, M0/ 1 in 38/22, and IIIA/IIIB/IIIC/IV in 16/13/9/22 patients, respectively.After SL, 11 patients were downstaged from T4a to T3, and 3 patients were downstaged from T4b to T4a.Moreover, 14 patients of P0 were identified as P1 or CY1, and 1 patient of H0 was identified as H1 after SL.As a result, post-SL Stages were IIB/IIIA/IIIB/IIIC/IV in 3/17/9/2/29 patients, respectively. In Stage III patients, staging was changed in 17 patients (44.7%) and the treatment strategies were changed in 9 patients (23.7%).In Stage IV cases, none of the patients changed staging and treatment strategies after SL.In conclusion, SL is useful for accurate staging and determining the treatment strategies in Stage III gastric cancer; however, re-evaluation is needed for the indication of SL in Stage IV gastric cancer.


Assuntos
Laparoscopia , Neoplasias Gástricas/patologia , Humanos , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/terapia
12.
Gan To Kagaku Ryoho ; 41(12): 2239-41, 2014 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-25731482

RESUMO

The ACTS-GC trial showed the efficacy of S-1 adjuvant chemotherapy in patients with pathological Stage II/III gastric cancer who had undergone D2 gastrectomy; however, T1 patients were excluded from this trial.In this study, we compared the prognosis of T1N2/3 gastric cancer with the outcomes of ACTS-GC.From 2000 to 2009, out of 480 patients with resected T1 gastric cancer, 27 patients(5.6%) were pN2/3.Six patients received S-1 adjuvant chemotherapy (group S), whereas 21 patients did not(group N).The 3-year overall survival rates of T1N0/1 and T1N2/3 were 91.7% and 71.3%, respectively. Among T1N2/3 gastric cancer patients, the 3-year survival rate and relapse-free survival rate were 100%/100% in group S and 72.7%/71.1% in group N, respectively. The prognosis of group N was poorer than that of the surgery-alone group in Stage II of ACTS-GC.Furthermore, 5 patients (23.8%) of group N had recurrences; the primary sites of recurrences were lymph nodes in 4 cases, and lymph nodes and liver in 1 case.The prognosis of T1N2/3 gastric cancer is poor; we should, therefore, consider evaluating the efficacy of adjuvant chemotherapy in T1N2/3 gastric cancer patients.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Idoso , Quimioterapia Adjuvante , Combinação de Medicamentos , Feminino , Gastrectomia , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
13.
Gan To Kagaku Ryoho ; 41(12): 1482-4, 2014 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-25731226

RESUMO

AIM: To assess the outcomes of preoperative colonic stent placement for obstructive colorectal cancer. PATIENTS AND METHODS: A total of 30 patients with colorectal cancer were treated after preoperative colonic metallic stent placement between July 2012 and March 2014. We reviewed their medical records to assess the usefulness of stent placement and the clinical course. The effects of various clinicopathological variables on post-operative complications were analyzed statistically. RESULTS: Stent insertion was effective in 93% of the 30 patients with obstructive colorectal cancer. Preoperative colonoscopy or enema for proximal colonic survey was possible in 70% of the patients after stent placement; colonic lesions requiring simultaneous resection were noted in 5 patients (24%). The mean interval between stent insertion and operation was 19 days, and 23%of the patients underwent laparoscopic surgery. Statistical analysis revealed that the occurrence of complications was associated with laparoscopic surgery and the amount of operative blood loss. CONCLUSION: Preoperative stent placement in patients with obstructive colorectal cancer is feasible and laparoscopic surgery can be selected after stent placement.


Assuntos
Neoplasias Colorretais/cirurgia , Íleus/cirurgia , Laparoscopia , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/complicações , Feminino , Humanos , Íleus/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Resultado do Tratamento
14.
Food Funct ; 4(12): 1835-42, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24191276

RESUMO

Advanced glycation end-products (AGE) have been implicated in aging and the pathogenesis of diabetic complications, inflammation, Alzheimer's disease, and cancer. AGE engage the cell surface receptor for AGE (RAGE), which in turn elicits intracellular signaling, leading to activation of NF-κB to cause deterioration of tissue homeostasis. AGE are not only formed within our bodies but are also derived from foods, endowing them with flavor. In the present study, we assessed the agonistic/antagonistic effects of food-derived AGE on RAGE signaling in a reporter assay system and found that low-molecular weight AGE can antagonize the action of AGE-BSA. Foods tested were Japanese soy sauce, coffee, cola, and red wine, all of which showed fluorescence characteristics of AGE. Soy sauce and coffee contained N(ε)-carboxymethyl-lysine (CML). Soy sauce, coffee, and red wine inhibited the RAGE ligand-induced activation of NF-κB, whereas cola had no effect on the ligand induction of NF-κB. The liquids were then fractionated into high-molecular weight (HMW) fractions and low-molecular weight (LMW) fractions. Soy sauce-, coffee-, and red wine-derived LMW fractions consistently inhibited the RAGE ligand induction of NF-κB, whereas the HMW fractions of these foods activated RAGE signaling. Using the LMW fraction of soy sauce as a model food-derived RAGE antagonist, we performed a plate-binding assay and found that the soy sauce LMW fractions competitively inhibited AGE-RAGE association. Further, this fraction significantly reduced AGE-dependent monocyte chemoattractant protein-1 (MCP-1) secretion from murine peritoneal macrophages. The LMF from soy sauce suppressed the AGE-induced RAGE trafficking to lipid rafts. These results indicate that small components in some, if not all, foods antagonize RAGE signaling and could exhibit beneficial effects on RAGE-related diseases.


Assuntos
Produtos Finais de Glicação Avançada/metabolismo , Microdomínios da Membrana/metabolismo , Receptores Imunológicos/agonistas , Alimentos de Soja/análise , Animais , Linhagem Celular , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Regulação para Baixo , Produtos Finais de Glicação Avançada/agonistas , Humanos , Microdomínios da Membrana/genética , Camundongos , Peso Molecular , NF-kappa B/genética , NF-kappa B/metabolismo , Transporte Proteico , Ratos , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/metabolismo , Transdução de Sinais
15.
Cancer Sci ; 104(6): 740-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23421467

RESUMO

The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor and its engagement by ligands such as high mobility group box 1 (HMGB1) is implicated in tumor growth and metastasis. Low molecular weight heparin (LMWH) has an antagonistic effect on the RAGE axis and is also reported to exert an antitumor effect beyond the known activity of anticoagulation. However, the link between the anti-RAGE and antitumor activities of LMWH has not yet to be fully elucidated. In this study, we investigated whether LMWH could inhibit tumor cell proliferation, invasion, and metastasis by blocking the RAGE axis using in vitro and in vivo assay systems. Stably transformed HT1080 human fibrosarcoma cell lines were obtained, including human full-length RAGE-overexpressing (HT1080(RAGE)), RAGE dominant-negative, intracellular tail-deleted RAGE-overexpressing (HT1080(dnRAGE)), and mock-transfected control (HT1080(mock)) cells. Confocal microscopy showed the expression of HMGB1 and RAGE in HT1080 cells. The LMWH significantly inhibited HMGB1-induced NFκB activation through RAGE using an NFκB-dependent luciferase reporter assay and the HT1080 cell lines. Overexpression of RAGE significantly accelerated, but dnRAGE expression attenuated HT1080 cell proliferation and invasion in vitro, along with similar effects on local tumor mass growth and lung metastasis in vivo. Treatment with LMWH significantly inhibited the migration, invasion, tumor formation, and lung metastasis of HT1080(RAGE) cells, but not of HT1080(mock) or HT1080(dnRAGE) cells. In conclusion, this study revealed that RAGE exacerbated the malignant phenotype of human fibrosarcoma cells, and that this exacerbation could be ameliorated by LMWH. It is suggested that LMWH has therapeutic potential in patients with certain types of malignant tumors.


Assuntos
Antineoplásicos/farmacologia , Fibrossarcoma/metabolismo , Heparina de Baixo Peso Molecular/farmacologia , Neoplasias Experimentais/metabolismo , Receptores Imunológicos/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Movimento Celular , Citometria de Fluxo , Proteína HMGB1/metabolismo , Humanos , Camundongos , Camundongos Nus , Microscopia Confocal , Invasividade Neoplásica/patologia , Neoplasias Experimentais/patologia , Ratos , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/efeitos dos fármacos , Transfecção
16.
Genes Cells ; 18(4): 302-14, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23410183

RESUMO

Glucolipotoxicity, which is exerted by free fatty acids (FFA) and prolonged hyperglycemia, is implicated in pancreatic ß-cell failure in diabetes. Pattern recognition receptors such as receptor for advanced glycation end products (RAGE) and toll-like receptors 2 and 4 could mediate danger signals in ß-cells. We examined whether RAGE contributes to ß-cell failure in a type 2 diabetes mouse model. Pancreatic islets were isolated from ob/ob, db/db, diet-induced obesity (DIO), RAGE-null (RAGE(-/-) ), and RAGE(+/+) wild-type (WT) control mice and dispersed into single cells for flow cytometry. RAGE expression was detected in insulin-positive ß-cells of ob/ob and db/db mice, but not of WT, DIO, or RAGE(-/-) mice: thus, inadequate leptin receptor signaling and RAGE expression may be linked. Compared with RAGE(+/+) db/db mice, RAGE(-/-) db/db mice showed higher ß-cell number and mass with less apoptosis as well as glucose tolerance with higher insulin secretion without any differences in serum levels of FFA and adiponectin. Palmitate or oleate pretreatment combined with a leptin antagonist induced RAGE expression, AGE-elicited apoptosis, and impaired glucose-stimulated insulin secretion by advanced glycation end products (AGE) in MIN6 cells. FFA elevation with concomitant AGE formation during prolonged hyperglycemia could cause ß-cell damage through insufficient leptin action and subsequent RAGE induction in type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Insulina/metabolismo , Leptina/metabolismo , Receptores Imunológicos/metabolismo , Adiponectina/sangue , Animais , Apoptose , Glicemia , Linhagem Celular , Proliferação de Células , Diabetes Mellitus Tipo 2/genética , Dieta Hiperlipídica , Ácidos Graxos não Esterificados/sangue , Expressão Gênica , Intolerância à Glucose , Produtos Finais de Glicação Avançada/metabolismo , Insulina/sangue , Células Secretoras de Insulina/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos/metabolismo , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/genética , Receptores para Leptina/metabolismo
17.
Gan To Kagaku Ryoho ; 40(12): 1690-2, 2013 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-24393890

RESUMO

Owing to its less invasiveness, endoscopic stent placement is a potential treatment option for gastric cancer patients with gastric outlet obstruction( GOO). We compared the clinical outcomes of stent placement with gastrojejunostomy( GJ) bypass in terms of postoperative oral intake status, duration of oral intake, and overall survival. Thirty-eight patients who had unresectable gastric cancer with GOO were enrolled in this study. The stent placement group was divided into 2 subgroups: group P comprising 9 patients who received palliative treatment; and group A comprising 12 patients who received aggressive chemotherapy. Stent placement was performed for almost all the patients who had massive peritoneal metastasis and poor performance status. Improvement in oral intake was achieved in 19( 90.5%) of 21 patients after stent placement. Moreover, oral intake improved significantly in patients who underwent chemotherapy after stent placement. The median duration of oral intake and median overall survival was shorter in group P (1.8 and 2.8 months, respectively) and group A (3.2 and 4.8 months, respectively) than in group GJ( 11.8 and 12.7 months, respectively). In conclusion, endoscopic stent placement is effective in improving the oral intake status; however, it may be insufficient to improve the duration of oral intake. Thus, further studies are needed to clarify the clinical benefit of stent placement.


Assuntos
Obstrução da Saída Gástrica/terapia , Stents , Neoplasias Gástricas/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Obstrução da Saída Gástrica/etiologia , Gastrostomia , Humanos , Jejunostomia , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Resultado do Tratamento
18.
Int J Oncol ; 42(2): 403-10, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23229642

RESUMO

Chromatin remodeling factors have been the subject of great interest in oncology. However, little is known about their role in pancreatic cancer. The objective of this study was to clarify the clinical significance of the SWItch/sucrose non-fermentable (SWI/SNF) complex in patients with pancreatic cancer. A total of 68 patients with pancreatic cancer who underwent R0, 1 resection were enrolled. Cancer tissues were processed to tissue microarray, then stained immunohistochemically by using antibody of SWI/SNF components; BRM, BRG1, BAF250a, BAF180 and BAF47. The correlation of expression levels and clinicopathological outcomes were analyzed, followed by the multivariate analysis of prognostic factors for overall survival. The expression levels of the SWI/SNF components were categorized as low or high according to the median value of Histoscore. Statistical analysis revealed that BRM expression was related to tumor size, T factor, M factor, lymphatic invasion and stage BRG1 expression to histology and stage BAF180 expression to tumor size and BAF47 expression to lymphatic invasion, respectively. Multivariate Cox proportional hazard analysis showed that high BRM and low BAF180 expression levels were independent predictors of worse survival in patients with pancreatic cancer. High BRM, and low BAF180 were also independent prognostic factors for poor survival in the subgroup with adjuvant gemcitabine. These results suggest that the specific cofactors of SWI/SNF chromatin remodeling complex certainly have roles in pancreatic cancer. High BRM, and low BAF180 are useful biomarkers for poor prognosis in pancreatic cancer.


Assuntos
Biomarcadores Tumorais/biossíntese , Proteínas Cromossômicas não Histona/biossíntese , Regulação Neoplásica da Expressão Gênica/genética , Fatores de Transcrição/biossíntese , Idoso , Biomarcadores Tumorais/genética , Núcleo Celular/genética , Montagem e Desmontagem da Cromatina/genética , DNA Helicases/biossíntese , Proteínas de Ligação a DNA/biossíntese , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/biossíntese , Neoplasias Pancreáticas , Proteína SMARCB1 , Análise Serial de Tecidos
19.
World J Surg Oncol ; 10: 109, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22703761

RESUMO

BACKGROUND: The guidelines established by the National Comprehensive Cancer Network do not describe mucinous histology as a clinical factor that should influence the therapeutic algorithm. However, previous studies show conflicting results regarding the prognosis of colorectal mucinous adenocarcinoma. In this study, we described the clinicopathological features of mucinous adenocarcinoma in Japan, to identify optimal therapeutic strategies. METHODS: 144 patients with mucinous and 2673 with non-mucinous adenocarcinomas who underwent primary resection in two major centers in Yokohama, Japan were retrospectively evaluated for clinicopathological features and treatment factors. A multivariate analysis for overall survival followed by the comparison of overall survival using Cox proportional hazard model were performed. RESULTS: Patients with mucinous adenocarcinoma had larger primary lesions, higher preoperative CEA levels, a deeper depth of invasion, higher rates of nodal and distant metastasis, and more metastatic sites. A multivariate analysis for overall survival revealed a mucinous histology to be an independent prognostic factor. In the subgroup analysis stratified by stage, Patients diagnosed as stageIII and IV disease had a worse survival in mucinous adenocarcinoma than non-mucinous, while survival did not differ significantly in patients diagnosed as Stage0-II disease. In stageIII, local recurrence in rectal cases and peritoneal dissemination were more frequently observed in patients with a mucinous histology. CONCLUSIONS: Our study indentified that mucinous adenocarcinoma was associated with a worse survival compared with non-mucinous in patients with stageIII and IV disease. In rectal StageIII disease with mucinous histology, additional therapy to control local recurrence followed by surgical resection may be a strategical alternative. Further molecular investigations considering genetic features of mucinous histology will lead to drug development and better management of peritoneal metastasis.


Assuntos
Adenocarcinoma Mucinoso/secundário , Adenocarcinoma Mucinoso/terapia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Adenocarcinoma Mucinoso/mortalidade , Idoso , Neoplasias Colorretais/mortalidade , Terapia Combinada , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
20.
Hepatogastroenterology ; 59(119): 2122-6, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22440248

RESUMO

BACKGROUND/AIMS: The phosphatase of regenerating liver-3 (PRL-3) is over expressed in several human cancers and associated with tumor progression, invasion and metastasis. However, the correlation between PRL-3 expression and clinical outcome in colorectal cancer (CRC) has not been investigated. This study examined the relationship between the relative expression of the PRL-3 gene to the clinicopathological factors and outcomes in patients with CRC. METHODOLOGY: Surgical specimens of cancer tissue and adjacent normal mucosa were obtained from 202 patients with untreated CRC. The relative expression level of PRL-3 mRNA in cancer and in the normal adjacent mucosa was measured using the quantitative real-time reverse-transcriptase PCR. RESULTS: PRL-3 expression was higher in cancer tissue than in the adjacent normal mucosa. The tumor location and liver metastasis were found to be related to the PRL-3 expression level. The overall survival differed significantly between patients with high PRL-3 expression and those with low expression. CONCLUSIONS: High expression of the PRL-3 gene might be a useful predictor of poor postoperative outcome in patients with CRC.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Colorretais/enzimologia , Proteínas de Neoplasias/análise , Proteínas Tirosina Fosfatases/análise , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Distribuição de Qui-Quadrado , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/secundário , Masculino , Análise Multivariada , Proteínas de Neoplasias/genética , Modelos de Riscos Proporcionais , Proteínas Tirosina Fosfatases/genética , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
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