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1.
Surg Today ; 2024 May 04.
Article in English | MEDLINE | ID: mdl-38702438

ABSTRACT

PURPOSE: There have been no adequate comparisons of the efficacy, safety, and efficiency of analgesia after laparoscopic colorectal resection (LAC), with and without epidural anesthesia (EDA). METHODS: This was a multicenter prospective observational study of patients undergoing LAC. The primary end point was the mean visual analog scale (VAS) score on postoperative days (PODs) 1-7. The secondary end points were the highest VAS, complication rate, days to first ambulation and fatigue, length of hospital stay, and time to commencement of surgery. RESULTS: We compared an EDA group (Group E, n = 48) and a no-EDA group (Group O, n = 48) after matching. The mean VAS was not significantly different between the groups (28.7 vs. 30.1, p = 0.288). On assessing the secondary end points, the highest VAS was not significantly different between the groups. In fact, the VAS was lower in Group E only on POD 2. There was no difference in the incidence of complications, the time to first postoperative evacuation was shorter in Group E, and postoperative hospitalization was similar. The time to surgery was shorter in Group O. CONCLUSION: These results suggest that LAC without EDA is a feasible option, but with the early and regular use of adjunctive measures to provide more stable analgesia.

2.
Int J Surg Case Rep ; 102: 107840, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36577264

ABSTRACT

INTRODUCTION: Intravenous tumor thrombosis is a rare condition in colorectal cancer and shows a locally aggressive biological behavior. We herein report three cases of colorectal cancer with tumor thrombosis in the inferior mesenteric vein (IMV) treated by colorectal resection combined with resection of the IMV under laparoscopic surgery. CASE PRESENTATION: In these three colorectal cancer patients with IMV tumor thrombus, IMV tumor thrombus was detected in all instances on preoperative computed tomography. Preoperative chemotherapy was also performed in one patient with concurrent liver metastasis. All patients underwent laparoscopic locally R0 resection; however, the pathological findings showed a positive margin for IMV resection in all patients. CLINICAL DISCUSSION: We reviewed 19 previously reported cases along with our 3 present cases and clarified the characteristics of colorectal cancer accompanied by IMV tumor thrombosis. IMV tumor thrombosis may be a risk factor for liver metastasis and R1 resection, and systemic treatment, including neoadjuvant chemotherapy (NAC), may be quite important. CONCLUSION: IMV tumor thrombosis may have a tendency to cause hematogenous metastasis. Systemic therapy, including NAC, may be useful, but since this is a rare condition, the accumulation of further cases is needed.

3.
Anticancer Res ; 41(4): 2117-2122, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33813422

ABSTRACT

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.


Subject(s)
Adenocarcinoma/diagnosis , Biomarkers, Tumor/genetics , Colorectal Neoplasms/diagnosis , Glycoproteins/genetics , Intercellular Signaling Peptides and Proteins/genetics , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Aged , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , Colorectal Neoplasms/surgery , Female , Gene Expression Regulation, Neoplastic , Glycoproteins/metabolism , Humans , Intercellular Signaling Peptides and Proteins/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Lymphatic Metastasis , Male , Middle Aged , Postoperative Period , Prognosis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Survival Analysis , Treatment Outcome
4.
Gan To Kagaku Ryoho ; 46(10): 1653-1655, 2019 Oct.
Article in Japanese | MEDLINE | ID: mdl-31631165

ABSTRACT

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.


Subject(s)
Disseminated Intravascular Coagulation , Sigmoid Neoplasms , Splenectomy , Female , Humans , Middle Aged , Postoperative Complications , Sigmoid Neoplasms/surgery
5.
Gan To Kagaku Ryoho ; 45(1): 145-147, 2018 Jan.
Article in Japanese | MEDLINE | ID: mdl-29362336

ABSTRACT

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.


Subject(s)
Gastrointestinal Stromal Tumors/surgery , Intestinal Neoplasms/surgery , Intestinal Perforation/surgery , Antineoplastic Agents/therapeutic use , Chemotherapy, Adjuvant , Gastrointestinal Stromal Tumors/complications , Gastrointestinal Stromal Tumors/drug therapy , Humans , Imatinib Mesylate/therapeutic use , Intestinal Neoplasms/complications , Intestinal Neoplasms/drug therapy , Intestinal Perforation/etiology , Male , Middle Aged , Prognosis , Recurrence , Time Factors
6.
Gan To Kagaku Ryoho ; 44(12): 1317-1319, 2017 Nov.
Article in Japanese | MEDLINE | ID: mdl-29394619

ABSTRACT

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.


Subject(s)
Abdominal Neoplasms/surgery , Abdominal Wall/surgery , Adenocarcinoma/surgery , Gallbladder Neoplasms/pathology , Abdominal Neoplasms/pathology , Abdominal Neoplasms/secondary , Abdominal Wall/pathology , Adenocarcinoma/drug therapy , Adenocarcinoma/secondary , Aged , Antimetabolites, Antineoplastic/therapeutic use , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Female , Gallbladder Neoplasms/drug therapy , Gallbladder Neoplasms/surgery , Humans , Recurrence , Time Factors , Gemcitabine
7.
Biochem Biophys Res Commun ; 479(3): 447-452, 2016 Oct 21.
Article in English | MEDLINE | ID: mdl-27641663

ABSTRACT

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.


Subject(s)
Gene Expression Profiling , Gene Expression Regulation , Receptor for Advanced Glycation End Products/blood , Schizophrenia/blood , Adult , Case-Control Studies , Female , Gene Deletion , Genetic Markers , Genetic Predisposition to Disease , Genotype , Glycation End Products, Advanced/blood , Haplotypes , Humans , Linkage Disequilibrium , Male , Middle Aged , Models, Genetic , Protein Carbonylation , Receptor for Advanced Glycation End Products/genetics , Regression Analysis , Schizophrenia/genetics
8.
Gan To Kagaku Ryoho ; 43(12): 1908-1910, 2016 Nov.
Article in Japanese | MEDLINE | ID: mdl-28133172

ABSTRACT

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.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Salvage Therapy , Stomach Neoplasms/drug therapy , Adenocarcinoma/surgery , Aged , Cisplatin/administration & dosage , Drug Combinations , Humans , Male , Neoadjuvant Therapy , Oxonic Acid/administration & dosage , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Tegafur/administration & dosage
9.
Gan To Kagaku Ryoho ; 42(10): 1268-70, 2015 Oct.
Article in Japanese | MEDLINE | ID: mdl-26489568

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Appendix/pathology , Carcinoma, Signet Ring Cell/drug therapy , Peritoneal Neoplasms/secondary , Sigmoid Neoplasms/drug therapy , Sigmoid Neoplasms/pathology , Aged , Carcinoma, Signet Ring Cell/surgery , Combined Modality Therapy , Fatal Outcome , Humans , Male , Middle Aged , Peritoneal Neoplasms/drug therapy , Sigmoid Neoplasms/surgery
10.
Gan To Kagaku Ryoho ; 42(10): 1289-91, 2015 Oct.
Article in Japanese | MEDLINE | ID: mdl-26489575

ABSTRACT

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.


Subject(s)
Stomach Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Receptor, ErbB-2/analysis , Stomach Neoplasms/chemistry , Treatment Outcome
11.
Gan To Kagaku Ryoho ; 42(12): 2142-4, 2015 Nov.
Article in Japanese | MEDLINE | ID: mdl-26805291

ABSTRACT

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.


Subject(s)
Colorectal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Blood Loss, Surgical , Colectomy/methods , Colorectal Neoplasms/pathology , Female , Humans , Length of Stay , Male , Middle Aged , Neoplasm Staging , Postoperative Complications , Retrospective Studies , Treatment Outcome
12.
Biochem J ; 463(1): 75-82, 2014 Oct 01.
Article in English | MEDLINE | ID: mdl-24995813

ABSTRACT

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.


Subject(s)
Cyclic AMP/metabolism , Macrophages, Peritoneal/metabolism , Receptors, Immunologic/metabolism , Signal Transduction , Animals , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Cyclic AMP/genetics , Inflammation/genetics , Inflammation/metabolism , Inflammation/pathology , Macrophages, Peritoneal/pathology , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Knockout , Protein Structure, Tertiary , Proteolysis , Receptor for Advanced Glycation End Products , Receptors, Immunologic/genetics , S100 Calcium Binding Protein beta Subunit/genetics , S100 Calcium Binding Protein beta Subunit/metabolism
13.
Gan To Kagaku Ryoho ; 41(12): 1482-4, 2014 Nov.
Article in Japanese | MEDLINE | ID: mdl-25731226

ABSTRACT

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.


Subject(s)
Colorectal Neoplasms/surgery , Ileus/surgery , Laparoscopy , Stents , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/complications , Female , Humans , Ileus/etiology , Male , Middle Aged , Postoperative Complications , Treatment Outcome
14.
Gan To Kagaku Ryoho ; 41(12): 2232-4, 2014 Nov.
Article in Japanese | MEDLINE | ID: mdl-25731480

ABSTRACT

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.


Subject(s)
Laparoscopy , Stomach Neoplasms/pathology , Humans , Neoplasm Staging , Prognosis , Stomach Neoplasms/therapy
15.
Gan To Kagaku Ryoho ; 41(12): 2239-41, 2014 Nov.
Article in Japanese | MEDLINE | ID: mdl-25731482

ABSTRACT

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.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Oxonic Acid/therapeutic use , Stomach Neoplasms/drug therapy , Tegafur/therapeutic use , Aged , Chemotherapy, Adjuvant , Drug Combinations , Female , Gastrectomy , Humans , Male , Neoplasm Staging , Prognosis , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery
16.
Food Funct ; 4(12): 1835-42, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24191276

ABSTRACT

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.


Subject(s)
Glycation End Products, Advanced/metabolism , Membrane Microdomains/metabolism , Receptors, Immunologic/agonists , Soy Foods/analysis , Animals , Cell Line , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Down-Regulation , Glycation End Products, Advanced/agonists , Humans , Membrane Microdomains/genetics , Mice , Molecular Weight , NF-kappa B/genetics , NF-kappa B/metabolism , Protein Transport , Rats , Receptor for Advanced Glycation End Products , Receptors, Immunologic/metabolism , Signal Transduction
17.
Genes Cells ; 18(4): 302-14, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23410183

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Type 2/metabolism , Insulin-Secreting Cells/metabolism , Leptin/metabolism , Receptors, Immunologic/metabolism , Adiponectin/blood , Animals , Apoptosis , Blood Glucose , Cell Line , Cell Proliferation , Diabetes Mellitus, Type 2/genetics , Diet, High-Fat , Fatty Acids, Nonesterified/blood , Gene Expression , Glucose Intolerance , Glycation End Products, Advanced/metabolism , Insulin/blood , Insulin-Secreting Cells/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Obese/metabolism , Receptor for Advanced Glycation End Products , Receptors, Immunologic/genetics , Receptors, Leptin/metabolism
18.
Cancer Sci ; 104(6): 740-9, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23421467

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/pharmacology , Fibrosarcoma/metabolism , Heparin, Low-Molecular-Weight/pharmacology , Neoplasms, Experimental/metabolism , Receptors, Immunologic/metabolism , Animals , Blotting, Western , Cell Line, Tumor , Cell Movement , Flow Cytometry , HMGB1 Protein/metabolism , Humans , Mice , Mice, Nude , Microscopy, Confocal , Neoplasm Invasiveness/pathology , Neoplasms, Experimental/pathology , Rats , Receptor for Advanced Glycation End Products , Receptors, Immunologic/drug effects , Transfection
19.
Int J Oncol ; 42(2): 403-10, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23229642

ABSTRACT

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.


Subject(s)
Biomarkers, Tumor/biosynthesis , Chromosomal Proteins, Non-Histone/biosynthesis , Gene Expression Regulation, Neoplastic/genetics , Transcription Factors/biosynthesis , Aged , Biomarkers, Tumor/genetics , Cell Nucleus/genetics , Chromatin Assembly and Disassembly/genetics , DNA Helicases/biosynthesis , DNA-Binding Proteins/biosynthesis , Female , Humans , Male , Middle Aged , Nuclear Proteins/biosynthesis , Pancreatic Neoplasms , SMARCB1 Protein , Tissue Array Analysis
20.
Gan To Kagaku Ryoho ; 40(12): 1690-2, 2013 Nov.
Article in Japanese | MEDLINE | ID: mdl-24393890

ABSTRACT

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.


Subject(s)
Gastric Outlet Obstruction/therapy , Stents , Stomach Neoplasms/complications , Aged , Aged, 80 and over , Female , Gastric Outlet Obstruction/etiology , Gastrostomy , Humans , Jejunostomy , Male , Middle Aged , Palliative Care , Treatment Outcome
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