Recently,undergraduate and postgraduate pharmaceutical education systems have been changing greatly in Japan.In 2006,undergraduate pharmacist program was changed from 4 years course to 6 years course to train higher-q...Recently,undergraduate and postgraduate pharmaceutical education systems have been changing greatly in Japan.In 2006,undergraduate pharmacist program was changed from 4 years course to 6 years course to train higher-quality pharmacists who can deal with the changes in the progression of medical technology and meet social demands for medication safety[1].As a postgraduate training system,pharmacy residency system was started in several hospital in 2002,and around 35 hospitals have pharmacy residency system at 2015[2].展开更多
Traffic at urban intersections frequently encounters unexpected obstructions,resulting in congestion due to uncooperative and priority-based driving behavior.This paper presents an optimal right-turn coordination syst...Traffic at urban intersections frequently encounters unexpected obstructions,resulting in congestion due to uncooperative and priority-based driving behavior.This paper presents an optimal right-turn coordination system for Connected and Automated Vehicles(CAVs)at single-lane intersections,particularly in the context of left-hand side driving on roads.The goal is to facilitate smooth right turns for certain vehicles without creating bottlenecks.We consider that all approaching vehicles share relevant information through vehicular communications.The Intersection Coordination Unit(ICU)processes this information and communicates the optimal crossing or turning times to the vehicles.The primary objective of this coordination is to minimize overall traffic delays,which also helps improve the fuel consumption of vehicles.By considering information from upcoming vehicles at the intersection,the coordination system solves an optimization problem to determine the best timing for executing right turns,ultimately minimizing the total delay for all vehicles.The proposed coordination system is evaluated at a typical urban intersection,and its performance is compared to traditional traffic systems.Numerical simulation results indicate that the proposed coordination system significantly enhances the average traffic speed and fuel consumption compared to the traditional traffic system in various scenarios.展开更多
In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting t...In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or intermediates.These processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS superfamily.Dysfunction of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative diseases.Therefore,it is important to understand the physiological and pathological roles of RAB proteins in brain function.RAB35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell migration.RAB35 is also involved in neurite outgrowth and turnover of synaptic vesicles.We generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and function.These mice exhibited defects in anxiety-related behaviors and spatial memory.Strikingly,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal lamination.In contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex development.Recent studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's disease.In this review,we provide an overview of the current understanding of subcellular functions of RAB35.We also provide insights into the physiological role of RAB35 in mammalian brain development and function,and discuss the involvement of RAB35 dysfunction in neurodegenerative diseases.展开更多
In the recent issue of the World Journal of Gastroenterology,Han et al compared the efficacy of and adverse reactions to bevacizumab versus lenvatinib as molecularly targeted agents in combination with interventional ...In the recent issue of the World Journal of Gastroenterology,Han et al compared the efficacy of and adverse reactions to bevacizumab versus lenvatinib as molecularly targeted agents in combination with interventional therapy and immunotherapy(IMT)to treat intermediate-to-advanced unresectable hepatocellular carcinoma.No significant differences in efficacy or adverse reactions were observed between bevacizumab and lenvatinib.This study is highly promising because in some regions,e.g.,Japan,the combination of molecularly targeted therapy with IMT is fixed because of insurance restrictions,and some molecularly targeted agents cannot be combined with IMT.Further studies using these three modalities are expected to be conducted in the future.Additionally,because advanced radiotherapy modalities have recently been established,the number of combinations continues to increase,and further evidence regarding combination therapy,which is the cornerstone of personalized medicine,needs to be accumulated.展开更多
AIM:To examine the efficacy of glycyrrhizin preparation(GL-p) in the treatment of a rat model of ulcerative colitis(UC).METHODS:Experimental colitis was induced by oral administration of dextran sodium sulfate.Rats wi...AIM:To examine the efficacy of glycyrrhizin preparation(GL-p) in the treatment of a rat model of ulcerative colitis(UC).METHODS:Experimental colitis was induced by oral administration of dextran sodium sulfate.Rats with colitis were intrarectally administered GL-p or saline.The extent of colitis was evaluated based on body weight gain,colon wet weight,and macroscopic damage score.The expression levels of pro-inflammatory cytokines and chemokines in the inflamed mucosa were measured by cytokine antibody array analysis.The effect of GL-p on myeloperoxidase(MPO) activity in the inflamed mucosa and purified enzyme was assayed.RESULTS:GL-p treatment significantly ameliorated the extent of colitis compared to sham treatment with saline.Cytokine antibody array analysis showed that GL-p treatment significantly decreased the expression levels of pro-inflammatory cytokines and chemokines,including interleukin(IL)-1β,IL-6,tumor necrosis factor-α,cytokine-induced neutrophil chemoattractant-2,and monocyte chemoattractant protein-1 in the inflamed mucosa.Furthermore,GL-p inhibited the oxidative activity of mucosal and purified MPO.CONCLUSION:GL-p enema has a therapeutic effect on experimental colitis in rats and may be useful in the treatment of UC.展开更多
The hepatic stellate cells in the liver are stimulated sustainably by chronic injury of the hepatocytes, activating myofibroblasts, which produce abundant collagen. Myofibroblasts are the major source of extracellular...The hepatic stellate cells in the liver are stimulated sustainably by chronic injury of the hepatocytes, activating myofibroblasts, which produce abundant collagen. Myofibroblasts are the major source of extracellular proteins during fibrogenesis, and may directly, or secreted products, contribute to carcinogenesis and tumor progression. Cancer-associated fibroblasts(CAFs) are one of the components of the tumor microenvironment that promote the proliferation and invasion of cancer cells by secreting various growth factors and cytokines. CAFs crosstalk with cancer cells stimulates tumor progression by creating a favorable microenvironment for progression, invasion, and metastasis through the epithelial-mesenchymal transition. Basic studies on CAFs have advanced, and the role of CAFs in tumors has been elucidated. In particular, for hepatocellular carcinoma, carcinogenesis from cirrhosis is a known fact, and participation of CAFs in carcinogenesis is supported. In this review, we discuss the current literature on the role of CAFs and CAF-related signaling in carcinogenesis, crosstalk with cancer cells, immunosuppressive effects, angiogenesis, therapeutic targets, and resistance to chemotherapy. The role of CAFs is important in cancer initiation and progression. CAF-targeted therapy may be effective for suppression not only of fibrosis but also cancer progression.展开更多
AIM： To estimate the contribution of autoimmune thrombocytopenia to hepatitis C virus-related liver cirrhosis （type C cirrhosis）, we evaluated the influence of splenectomy upon platelet-associated immunoglobulin G ...AIM： To estimate the contribution of autoimmune thrombocytopenia to hepatitis C virus-related liver cirrhosis （type C cirrhosis）, we evaluated the influence of splenectomy upon platelet-associated immunoglobulin G （PAIgG） levels and platelet numbers. METHODS： PAIgG titers and immune markers were determined in 24 type C cirrhotic patients with an intact spleen, 17 type C cirrhotic patients submitted to splenectomy, and 21 non-C cirrhosis with an intact spleen. RESULTS： Thrombocytopenia （PLT〈15×10^4/μL） in type C cirrhosis was diagnosed in all patients with an intact spleen, 8 patients submitted to splenectomy, and in 19 non-C cirrhosis with intact spleen. Elevated titers of PAIgG at more than 25.0 ng/107cells were detected in all cirrhotic patients except for one splenectomized patient. PAIgG titers （ng/10^7cells） were significantly higher in the type C cirrhosis with an intact spleen （247.9 ± 197.0） compared with the splenectomized patients （125.6±87.8） or non-C cirrhosis （152.4± 127.4）. PAIgG titers were negatively correlated with platelet counts in type C cirrhotic patients with an intact spleen. In comparison with the type C cirrhosis with an intact spleen, the splenectomized patients had a reduced CD4/CD8 ratio and serum neopterin levels. The spleen index （cm^2） was negatively correlated with platelet counts in the non-C cirrhosis, but not in the type C cirrhosis. CONCLUSION： Our data indicate that the autoimmune mechanism plays an important role in thrombocytosis complicated by HCV-positive cirrhosis. In addition, splenectomy may impair T cells function through, at least in part, a reduction of CD4/CD8 ratio, consequently suppressing PAIgG production.展开更多
AIM: To compare cases of xanthogranulomatous cholecystitis(XGC) and advanced gallbladder cancer and discuss the differential diagnoses and surgical options.METHODS: From April 2000 to December 2013, 6 XGC patients rec...AIM: To compare cases of xanthogranulomatous cholecystitis(XGC) and advanced gallbladder cancer and discuss the differential diagnoses and surgical options.METHODS: From April 2000 to December 2013, 6 XGC patients received extended surgical resections. During the same period, 16 patients were proven to have gallbladder(GB) cancer, according to extended surgical resection. Subjects chosen for analysis in this study were restricted to cases of XGC with indistinct borders with the liver as it is often difficult to distinguish these patients from those with advanced GB cancer. We compared the clinical features and computed tomography findings between XGC and advanced GB cancer. The following clinical features were retrospectively assessed: age, gender, symptoms, and tumor markers. As albumin and the neutrophil/lymphocyte ratio(NLR) are prognostic in several cancers, we compared serum albumin levels and the NLR between the two groups. The computerized tomography findings were used to compare the two diseases, determine the coexistence of gallstones, the pattern of GB thickening(focal or diffuse), the presence of a hypoattenuated intramural nodule, and continuity of the mucosal line.RESULTS: Based on the preoperative image findings, we suspected GB carcinoma in all cases includingXGC in this series. In addition, by pathological examination, we found that the group of patients with XGC developed inflammatory disease after surgery. Patients with XGC tended to have abdominal pain(4/6, 67%). However, there was no significant difference in clinical symptoms, including fever, between the two groups. Serum albumin and NLR were also similar in the two groups. Serum tumor markers, such as carcinoembryonic antigen(CEA) and carbohydrate antigen 19-9(CA19-9), tended to increase in patients with GB cancer. However, no significant differences in tumor markers were identified. On the other hand, gallstones were more frequently observed in patients with XGC(5/6, 83%) than in patients with GB cancer(4/16, 33%)(P = 0.0116). A hypoattenuated intramural nodule was found in 3 patients with XGC(3/6, 50%), but in only 1 patient with GB cancer(1/16, 6%)(P = 0.0024). The GB thickness, continuous mucosal line, and bile duct dilatation showed no significant differences between XGC and GB cancer.CONCLUSION: Although XGC is often difficult to differentiate from GB carcinoma, it is possible to obtain an accurate diagnosis by careful intraoperative gross observation, and several intraoperative frozen sections.展开更多
Transcatheter arterial chemoembolization(TACE) is widely accepted as a treatment for patients with hepatocellular carcinoma(HCC) in the intermediate stage according to the Barcelona Clinic Liver Cancer(BCLC) guideline...Transcatheter arterial chemoembolization(TACE) is widely accepted as a treatment for patients with hepatocellular carcinoma(HCC) in the intermediate stage according to the Barcelona Clinic Liver Cancer(BCLC) guidelines. Recently, balloon-occluded TACE(B-TACE) was developed in Japan. Despite the lack of a clear definition, B-TACE is generally defined as the infusion of emulsion of chemotherapeutic agents with lipiodol followed by gelatin particles under the occlusion of feeding arteries by a microballoon catheter, which leads to the dense lipiodol emulsion(LE) accumulation in HCC nodules. This phenomenon cannot be explained only by the prevention of proximal migration and leakage of embolization materials; it further involves causing local changes in the hemodynamics of the surrounding occlusion artery and targeted HCC nodules. Balloon-occluded arterial stump pressure plays an important role in the dense LE accumulation in targeted HCC nodules. Although randomized controlled trials comparing the therapeutic effect and the prognosis of B-TACE to those of the other TACE procedures, such as conventional-TACE and drug-eluting beads TACE, are still lacking, B-TACE is thought to be a promising treatment. The purpose of this review is to summarize the mechanism, therapeutic effect, indication, prognosis and complications of BTACE.展开更多
AIM： To determine the feasibility of performing computed tomography （CT）-guided transpulmonary radiofrequency ablation （RFA） for hepatocellular carcinoma （HCC） located in the hepatic dome. METHODS： A total of ...AIM： To determine the feasibility of performing computed tomography （CT）-guided transpulmonary radiofrequency ablation （RFA） for hepatocellular carcinoma （HCC） located in the hepatic dome. METHODS： A total of seven patients with HCC comprising seven nodules located in the hepatic dome were treated from April 2004 to December 2004. CTguided transpulmonary RFA was performed using a cool-tip type electrode （Radionics Company） based on a standardized energy protocol. All tumors located in the hepatic dome were not detectable by the usual ultrasound （US） methods. The lesion diameters ranged from 15 to 27 mm. RESULTS： RFA was technically feasible in all the patients. The puncture procedure was performed twice or less and the total average performance time was 40.6 min. Local tumor control was achieved in all the patients. The necrosis diameter ranged from 25 to 35 mm. The mean follow-up period was 9.6 （7-14 mo） mo. There was no local recurrenceat the follow-up points. Pneumothorax requiring pleural drainage was the main complication, which was observed in two of the seven patients （28.6%）. However, it improved with chest drainage tube, and the tube could be removed within 2-3 d. No other major complications were observed.CONCLUSION： CT-guided puncture is useful for the treatment of tumors located in the hepatic dome which are hardly detectable by US, even though pneumothorax sometimes may occur as a complication. In the cases with adhesion in the pleura for which artificial pleural effusion methods are not appropriate, CT-guided RFA is thus considered to be an alternative treatment for HCC located in the hepatic dome.展开更多
Hepatic inflammatory pseudotumor （IPT） is a rare benign non-neoplastic lesion characterized by proliferating fibrous tissue infiltrated by inflammatory cells. The exact etiology of IPT remains unclear. Although the ...Hepatic inflammatory pseudotumor （IPT） is a rare benign non-neoplastic lesion characterized by proliferating fibrous tissue infiltrated by inflammatory cells. The exact etiology of IPT remains unclear. Although the association of IPT with systemic inflammatory disorders has been well established, a specific relationship with cholangitis is distinctly rare. We report a case of spontaneous regression of hepatic IPT with primary biliary cirrhosis （PBC）. To date, only two cases of IPT with PBC have been reported. In our case, however, IPT developed during the course of improvement of cholangitis of PBC induced by effective treatment, differing from two previously reported cases. Our case indicates that the development of IPT does not also relate to the activity of cholangitis and/or hyper gamma-globulinemia, since our case was confirmed radiologically to be free of IPT when biliary enzymes and immunoglobulins were much higher than the corresponding values on admission. Comparison of our case with the two previously reported cases suggests that IPT occurring with PBC does not represent the same disease entity or be a bystander for PBC.展开更多
AIM:To investigate whether endoscopic submucosal dissection(ESD) can be safely performed at small clinics,such as the Shirakawa Clinic.METHODS:One thousand forty-seven ESDs to treat gastrointestinal tumors were perfor...AIM:To investigate whether endoscopic submucosal dissection(ESD) can be safely performed at small clinics,such as the Shirakawa Clinic.METHODS:One thousand forty-seven ESDs to treat gastrointestinal tumors were performed at the Shirakawa Clinic from April 2006 to March 2011.The efficacy,technical feasibility and associated complications of the procedures were assessed.The ESD procedures were performed by five endoscopists.Sedation was induced with propofol for esophagogastorduodenal ESD.RESULTS:One thousand forty-seven ESDs were performed to treat 64 patients with esophageal cancer(E),850 patients with gastric tumors(G:764 patients with cancer,82 patients with adenomas and four others),four patients with duodenal cancer(D) and 129 patients with colorectal tumors(C:94 patients with cancer,21 patients with adenomas and 14 others).The en bloc resection rate was 94.3%(E:96.9%,G:95.8%,D:100%,C:79.8%).The median operation time was 46 min(range:4-360 min) and the mean size of the resected specimens was 18 mm(range:2-150 mm).No mortal complications were observed in association with the ESD procedures.Perforation occurred in 12 cases(1.1%,E:1 case,G:9 cases,D:1 case,C:1 case) and postoperative bleeding occurred in 53 cases(5.1%,G:51 cases,D:1 case,C:1 case);however,no case required either emergency surgery or blood transfusion.All of the perforations and postperative bleedings were resolved by endoscopic clipping or hemostasis.The other problematic complication observed was pneumonia,which was treated with conservative therapy.CONCLUSION:ESD can be safely performed in a clinic with established therapeutic methods and medical services to address potential complications.展开更多
Endoscopic submucosal dissection(ESD)has been proposed as the gold standard in the treatment of early gastric cancer because it facilitates a more accurate histological assessment and reduces the risk of tumor recurre...Endoscopic submucosal dissection(ESD)has been proposed as the gold standard in the treatment of early gastric cancer because it facilitates a more accurate histological assessment and reduces the risk of tumor recurrence.However,the time course of ESD for large gastric tumors is frequently prolonged because of the tumor size and technical difficulties and typically requires higher doses of sedative and pain-controlling drugs.Sedative or anesthetic drugs such as midazolam or propofol are used during the procedure.Therapeutic endoscopy of early gastric cancers can often be performed with only moderate sedation.Compared with midazolam,propofol has a very fast onset of action,short plasma half-life and time to achieve sedation,faster time to recovery and discharge,and results in higher patient satisfaction.For overall success,maintaining safety and stability not only during the procedure but also subsequently in the recovery room and ward is necessary.In obese patients,it is recommended that the injected dose be based on a calculated standard weight.Cooperation between gastroenterologists,surgeons,and anesthesiologists is imperative for a successful ESD procedure.展开更多
AIM： To evaluate the effect of three interventional treatments involving transvenous obliteration for the treatment of gastric varices, and to compare the efficacy and adverse effects of these methods, METHODS： From...AIM： To evaluate the effect of three interventional treatments involving transvenous obliteration for the treatment of gastric varices, and to compare the efficacy and adverse effects of these methods, METHODS： From 1995 to 2004, 93 patients with gastric fundal varices underwent interventional radiologic embolotherapy at our hospital. Of the 93 patients, 75 were treated with the balloon-occluded retrograde transvenous obliteration （BRTO） procedure; 8 were with the percutaneous transhepatic obliteration （PTO） procedure; and 10 were with the combined BRTO and PTO therapy. A follow-up evaluation examined the rates of survival, recurrence and rebleeding of the gastric varices, worsening of esophageal varices and complications in each group. RESULTS： The BRTO, PTO, and combined therapy were technically successful in 81% （75/93）, 44% （8/18）, and 100% （10/10） patients, respectively. Recurrence of gastric varices was found in 3 patients in the BRTO group and in 3 patients in the PTO group. Rebleeding was observed in 1 patient in the BRTO group and in 1 patient in the PTO group. The 1- and 3-year survival rates were 98% and 87% in the patients without hepatocellular carcinoma （HCC） in the BRTO group, 100% and 100% in the PTO group, and 90% and 75% in the combined therapy group, respectively. CONCLUSION： Combined BRTO and PTO therapy may rescue cases with uncontrollable gastric fundal varices that remained even after treatment with BRTO and/or PTO, though there were limitations of our study, including retrospective nature and discrepancy in sample size between the BRTO, PTO and combined therapy groups.展开更多
MK615, a compound extracted from the Japanese apricot "Prunus mume " has been reported to have in vitro anti-tumor activities against several cancer cell lines,including hepatocellular carcinoma(HCC). Howeve...MK615, a compound extracted from the Japanese apricot "Prunus mume " has been reported to have in vitro anti-tumor activities against several cancer cell lines,including hepatocellular carcinoma(HCC). However, the clinical effects and feasibility of administering MK615for patients with HCC were unknown. We experienced a case with advanced HCC for which MK615 was effective against both lymph node and pulmonary metastases. A 60-year-old female underwent surgical resection of a 9 cm HCC in the right lobe. The pathological diagnosis was moderately differentiated HCC with vascular invasion. The HCC recurred in the liver 8 mo after the surgery. Radiofrequency ablation and transarterial infusion chemotherapy were performed, but the recurrence was not controlled. One year after the intrahepatic recurrence, pulmonary and lymph metastasis appeared.Sorafenib was administered, but was not effective.Then, MK615 was administered as a final alternative therapy after informed consent was obtained from the patient. Three months later, her alpha-fetoprotein level decrease and both the lymph node and pulmonary metastases decreased in size. The patient has survived for more than 17 mo after the MK615 administration, and was in good condition. Although further investigations are necessary to clarify its safety and efficacy in humans, MK615 may be useful for the treatment of HCC,without serious adverse effects.展开更多
AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs ...AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B,5-HT3 and 5-HT4 receptor antagonist administration.The force transducers were implanted on the serosal surfaces of the gastric antrum,terminal ileum,ileocecal sphincter and colon.Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state.The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed.RESULTS:5-HT2B,5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum.The 5-HT3 and 5-HT4 receptor antagonists inhibited phaseⅢof the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity.In the proximal colon,the inhibitory effect was dose dependent.Dose dependency,however,was not observed in the distal colon.The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.CONCLUSION:The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity.The5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.展开更多
AIM To investigate the significance of heat shock protein 110(HSP110) in gastric cancer(GC) patients with peritoneal metastasis undergoing hyperthermochemotherapy.METHODS Primary GC patients(n = 14) with peritoneal me...AIM To investigate the significance of heat shock protein 110(HSP110) in gastric cancer(GC) patients with peritoneal metastasis undergoing hyperthermochemotherapy.METHODS Primary GC patients(n = 14) with peritoneal metastasis or positive peritoneal lavage cytology who underwent distal or total gastrectomy between April 2000 and December 2011 were enrolled in this study. The patients underwent postoperative intraperitoneal hyperthermo-chemotherapy using a Thermotron RF-8 heating device two weeks after surgery. We analyzed nuclear HSP110 expression in surgically resected tumors using immunohistochemistry. Additionally, the effect of HSP110 suppression on hyptherthermochemosensitivity was assessed in vitro in the MKN45 GC cell line using the HSP inhibitor KNK437. RESULTS HSP110 immnohistochemical staining in 14 GC patients showed that five(35.7%) samples belonged to the low expression group, and nine(64.3%) samples belonged to the high expression group. Progression-free survival was significantly shorter in the HSP110 high-expression group than in the low-expression group(P = 0.0313). However, no significant relationships were identified between HSP110 expression and the clinicopathological characteristics of patients. Furthermore, high HSP110 expression was not an independent prognostic factor in GC patients with peritoneal metastasis(P = 0.0625). HSP110 expression in MKN45 cells was suppressed by KNK437 at the hyperthermic temperature of 43 ℃ in vitro. Comparison of MKN45 cell proliferation in the presence and absence of KNK437 at 43 ℃, revealed that proliferation was significantly decreased when HSP110 was inhibited by KNK437. Additionally, HSP110 suppression via HSP inhibitor treatment increased cellular sensitivity to hyperthermo-chemotherapy in vitro.CONCLUSION The expression of nuclear HSP110 in GC patients might be a new marker of chemosensitivity and a therapeutic target for patients who are tolerant to existing hyperthermo-chemotherapies.展开更多
AIM： To define the clinical characteristics, and to as- sess the management of colonoscopic complications at a local clinic. METHODS： A retrospective review of the medical re- cords was performed for the patients wi...AIM： To define the clinical characteristics, and to as- sess the management of colonoscopic complications at a local clinic. METHODS： A retrospective review of the medical re- cords was performed for the patients with iatrogenic colon perforations after endoscopy at a local clinic be- tween April 2006 and December 2010. Data obtained from a tertiary hospital in the same region were also analyzed. The underlying conditions, clinical presenta- tions, perforation locations, treatment types （operative or conservative） and outcome data for patients at the local clinic and the tertiary hospital were compared. RESULTS： A total of 10 826 colonoscopies, and 2625 therapeutic procedures were performed at a local clinic and 32 148 colonoscopies, and 7787 therapeutic proce-dures were performed at the tertiary hospital. The clinic had no perforations during diagnostic colonoscopy and 8 （0.3%） perforations were determined to be related to therapeutic procedures. The perforation rates in each therapeutic procedure were 0.06% （1/1609） in polyp- ectomy, 0.2% （2/885） in endoscopic mucosal resection （EMR）, and 3.8% （5/131） in endoscopic submucosal dis- section （ESD）. Perforation rates for ESD were significantly higher than those for polypectomy or EMR （P 〈 0.01）. All of these patients were treated conservatively. On the oth- er hand, three （0.01%） perforation cases were observed among the 24 361 diagnostic procedures performed, and these cases were treated with surgery in a tertiary hospi- tal. Six perforations occurred with therapeutic endoscopy （perforation rate, 0.08%; 1 per 1298 procedures）. Perfo- ration rates for specific procedure types were 0.02% （1 per 5500） for polypectomy, 0.17% （1 per 561） for EMR, 2.3% （1 per 43） for ESD in the tertiary hospital. There were no differences in the perforation rates for each therapeutic procedure between the clinic and the tertiary hospital. The incidence of iatrogenic perforation requiring surgical treatment was quite low in both the clinic and the tertiary hospital. No procedure-related mortalities occurred. Performing closure with endoscopic clipping reduced the C-reactive protein （CRP） titers. The mean maximum CRP titer was 2.9：1：1.6 mg/dL with clipping and 9.7 ＋ 6.2 mg/dL without clipping, respectively （P 〈 0.05）. An operation is indicated in the presence of a large perforation, and in the setting of generalized peritonitis or ongoing sepsis. Although we did not experience such case in the clinic, patients with large perforations should be immediately transferred to a tertiary hospital. Good relationships between local clinics and nearby tertiary hospitals should therefore be maintained. CONCLUSION： It was therefore found to be possible to perform endoscopic treatment at a local clinic when sufficient back up was available at a nearby tertiary hospital.展开更多
文摘Recently,undergraduate and postgraduate pharmaceutical education systems have been changing greatly in Japan.In 2006,undergraduate pharmacist program was changed from 4 years course to 6 years course to train higher-quality pharmacists who can deal with the changes in the progression of medical technology and meet social demands for medication safety[1].As a postgraduate training system,pharmacy residency system was started in several hospital in 2002,and around 35 hospitals have pharmacy residency system at 2015[2].
基金supported by the Japan Society for the Promotion of Science(JSPS)Grants-in-Aid for Scientific Research(C)23K03898.
文摘Traffic at urban intersections frequently encounters unexpected obstructions,resulting in congestion due to uncooperative and priority-based driving behavior.This paper presents an optimal right-turn coordination system for Connected and Automated Vehicles(CAVs)at single-lane intersections,particularly in the context of left-hand side driving on roads.The goal is to facilitate smooth right turns for certain vehicles without creating bottlenecks.We consider that all approaching vehicles share relevant information through vehicular communications.The Intersection Coordination Unit(ICU)processes this information and communicates the optimal crossing or turning times to the vehicles.The primary objective of this coordination is to minimize overall traffic delays,which also helps improve the fuel consumption of vehicles.By considering information from upcoming vehicles at the intersection,the coordination system solves an optimization problem to determine the best timing for executing right turns,ultimately minimizing the total delay for all vehicles.The proposed coordination system is evaluated at a typical urban intersection,and its performance is compared to traditional traffic systems.Numerical simulation results indicate that the proposed coordination system significantly enhances the average traffic speed and fuel consumption compared to the traditional traffic system in various scenarios.
基金supported by the Japan Society for the Promotion of Science KAKENHI(grant Nos.23K05678 to IM,19H05711 and 20H00466 to KS)the Joint Research Program of Institute for Molecular and Cellular Regulation,Gunma University(to KS)。
文摘In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or intermediates.These processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS superfamily.Dysfunction of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative diseases.Therefore,it is important to understand the physiological and pathological roles of RAB proteins in brain function.RAB35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell migration.RAB35 is also involved in neurite outgrowth and turnover of synaptic vesicles.We generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and function.These mice exhibited defects in anxiety-related behaviors and spatial memory.Strikingly,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal lamination.In contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex development.Recent studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's disease.In this review,we provide an overview of the current understanding of subcellular functions of RAB35.We also provide insights into the physiological role of RAB35 in mammalian brain development and function,and discuss the involvement of RAB35 dysfunction in neurodegenerative diseases.
文摘In the recent issue of the World Journal of Gastroenterology,Han et al compared the efficacy of and adverse reactions to bevacizumab versus lenvatinib as molecularly targeted agents in combination with interventional therapy and immunotherapy(IMT)to treat intermediate-to-advanced unresectable hepatocellular carcinoma.No significant differences in efficacy or adverse reactions were observed between bevacizumab and lenvatinib.This study is highly promising because in some regions,e.g.,Japan,the combination of molecularly targeted therapy with IMT is fixed because of insurance restrictions,and some molecularly targeted agents cannot be combined with IMT.Further studies using these three modalities are expected to be conducted in the future.Additionally,because advanced radiotherapy modalities have recently been established,the number of combinations continues to increase,and further evidence regarding combination therapy,which is the cornerstone of personalized medicine,needs to be accumulated.
文摘AIM:To examine the efficacy of glycyrrhizin preparation(GL-p) in the treatment of a rat model of ulcerative colitis(UC).METHODS:Experimental colitis was induced by oral administration of dextran sodium sulfate.Rats with colitis were intrarectally administered GL-p or saline.The extent of colitis was evaluated based on body weight gain,colon wet weight,and macroscopic damage score.The expression levels of pro-inflammatory cytokines and chemokines in the inflamed mucosa were measured by cytokine antibody array analysis.The effect of GL-p on myeloperoxidase(MPO) activity in the inflamed mucosa and purified enzyme was assayed.RESULTS:GL-p treatment significantly ameliorated the extent of colitis compared to sham treatment with saline.Cytokine antibody array analysis showed that GL-p treatment significantly decreased the expression levels of pro-inflammatory cytokines and chemokines,including interleukin(IL)-1β,IL-6,tumor necrosis factor-α,cytokine-induced neutrophil chemoattractant-2,and monocyte chemoattractant protein-1 in the inflamed mucosa.Furthermore,GL-p inhibited the oxidative activity of mucosal and purified MPO.CONCLUSION:GL-p enema has a therapeutic effect on experimental colitis in rats and may be useful in the treatment of UC.
基金Supported by Research Program on Hepatitis from Japan Agency for Medical Research and development,AMED
文摘The hepatic stellate cells in the liver are stimulated sustainably by chronic injury of the hepatocytes, activating myofibroblasts, which produce abundant collagen. Myofibroblasts are the major source of extracellular proteins during fibrogenesis, and may directly, or secreted products, contribute to carcinogenesis and tumor progression. Cancer-associated fibroblasts(CAFs) are one of the components of the tumor microenvironment that promote the proliferation and invasion of cancer cells by secreting various growth factors and cytokines. CAFs crosstalk with cancer cells stimulates tumor progression by creating a favorable microenvironment for progression, invasion, and metastasis through the epithelial-mesenchymal transition. Basic studies on CAFs have advanced, and the role of CAFs in tumors has been elucidated. In particular, for hepatocellular carcinoma, carcinogenesis from cirrhosis is a known fact, and participation of CAFs in carcinogenesis is supported. In this review, we discuss the current literature on the role of CAFs and CAF-related signaling in carcinogenesis, crosstalk with cancer cells, immunosuppressive effects, angiogenesis, therapeutic targets, and resistance to chemotherapy. The role of CAFs is important in cancer initiation and progression. CAF-targeted therapy may be effective for suppression not only of fibrosis but also cancer progression.
文摘AIM： To estimate the contribution of autoimmune thrombocytopenia to hepatitis C virus-related liver cirrhosis （type C cirrhosis）, we evaluated the influence of splenectomy upon platelet-associated immunoglobulin G （PAIgG） levels and platelet numbers. METHODS： PAIgG titers and immune markers were determined in 24 type C cirrhotic patients with an intact spleen, 17 type C cirrhotic patients submitted to splenectomy, and 21 non-C cirrhosis with an intact spleen. RESULTS： Thrombocytopenia （PLT〈15×10^4/μL） in type C cirrhosis was diagnosed in all patients with an intact spleen, 8 patients submitted to splenectomy, and in 19 non-C cirrhosis with intact spleen. Elevated titers of PAIgG at more than 25.0 ng/107cells were detected in all cirrhotic patients except for one splenectomized patient. PAIgG titers （ng/10^7cells） were significantly higher in the type C cirrhosis with an intact spleen （247.9 ± 197.0） compared with the splenectomized patients （125.6±87.8） or non-C cirrhosis （152.4± 127.4）. PAIgG titers were negatively correlated with platelet counts in type C cirrhotic patients with an intact spleen. In comparison with the type C cirrhosis with an intact spleen, the splenectomized patients had a reduced CD4/CD8 ratio and serum neopterin levels. The spleen index （cm^2） was negatively correlated with platelet counts in the non-C cirrhosis, but not in the type C cirrhosis. CONCLUSION： Our data indicate that the autoimmune mechanism plays an important role in thrombocytosis complicated by HCV-positive cirrhosis. In addition, splenectomy may impair T cells function through, at least in part, a reduction of CD4/CD8 ratio, consequently suppressing PAIgG production.
文摘AIM: To compare cases of xanthogranulomatous cholecystitis(XGC) and advanced gallbladder cancer and discuss the differential diagnoses and surgical options.METHODS: From April 2000 to December 2013, 6 XGC patients received extended surgical resections. During the same period, 16 patients were proven to have gallbladder(GB) cancer, according to extended surgical resection. Subjects chosen for analysis in this study were restricted to cases of XGC with indistinct borders with the liver as it is often difficult to distinguish these patients from those with advanced GB cancer. We compared the clinical features and computed tomography findings between XGC and advanced GB cancer. The following clinical features were retrospectively assessed: age, gender, symptoms, and tumor markers. As albumin and the neutrophil/lymphocyte ratio(NLR) are prognostic in several cancers, we compared serum albumin levels and the NLR between the two groups. The computerized tomography findings were used to compare the two diseases, determine the coexistence of gallstones, the pattern of GB thickening(focal or diffuse), the presence of a hypoattenuated intramural nodule, and continuity of the mucosal line.RESULTS: Based on the preoperative image findings, we suspected GB carcinoma in all cases includingXGC in this series. In addition, by pathological examination, we found that the group of patients with XGC developed inflammatory disease after surgery. Patients with XGC tended to have abdominal pain(4/6, 67%). However, there was no significant difference in clinical symptoms, including fever, between the two groups. Serum albumin and NLR were also similar in the two groups. Serum tumor markers, such as carcinoembryonic antigen(CEA) and carbohydrate antigen 19-9(CA19-9), tended to increase in patients with GB cancer. However, no significant differences in tumor markers were identified. On the other hand, gallstones were more frequently observed in patients with XGC(5/6, 83%) than in patients with GB cancer(4/16, 33%)(P = 0.0116). A hypoattenuated intramural nodule was found in 3 patients with XGC(3/6, 50%), but in only 1 patient with GB cancer(1/16, 6%)(P = 0.0024). The GB thickness, continuous mucosal line, and bile duct dilatation showed no significant differences between XGC and GB cancer.CONCLUSION: Although XGC is often difficult to differentiate from GB carcinoma, it is possible to obtain an accurate diagnosis by careful intraoperative gross observation, and several intraoperative frozen sections.
文摘Transcatheter arterial chemoembolization(TACE) is widely accepted as a treatment for patients with hepatocellular carcinoma(HCC) in the intermediate stage according to the Barcelona Clinic Liver Cancer(BCLC) guidelines. Recently, balloon-occluded TACE(B-TACE) was developed in Japan. Despite the lack of a clear definition, B-TACE is generally defined as the infusion of emulsion of chemotherapeutic agents with lipiodol followed by gelatin particles under the occlusion of feeding arteries by a microballoon catheter, which leads to the dense lipiodol emulsion(LE) accumulation in HCC nodules. This phenomenon cannot be explained only by the prevention of proximal migration and leakage of embolization materials; it further involves causing local changes in the hemodynamics of the surrounding occlusion artery and targeted HCC nodules. Balloon-occluded arterial stump pressure plays an important role in the dense LE accumulation in targeted HCC nodules. Although randomized controlled trials comparing the therapeutic effect and the prognosis of B-TACE to those of the other TACE procedures, such as conventional-TACE and drug-eluting beads TACE, are still lacking, B-TACE is thought to be a promising treatment. The purpose of this review is to summarize the mechanism, therapeutic effect, indication, prognosis and complications of BTACE.
基金Supported by the grant of Center of E-xcellence,Biomedical Research Using Accelerator Technology
文摘AIM： To determine the feasibility of performing computed tomography （CT）-guided transpulmonary radiofrequency ablation （RFA） for hepatocellular carcinoma （HCC） located in the hepatic dome. METHODS： A total of seven patients with HCC comprising seven nodules located in the hepatic dome were treated from April 2004 to December 2004. CTguided transpulmonary RFA was performed using a cool-tip type electrode （Radionics Company） based on a standardized energy protocol. All tumors located in the hepatic dome were not detectable by the usual ultrasound （US） methods. The lesion diameters ranged from 15 to 27 mm. RESULTS： RFA was technically feasible in all the patients. The puncture procedure was performed twice or less and the total average performance time was 40.6 min. Local tumor control was achieved in all the patients. The necrosis diameter ranged from 25 to 35 mm. The mean follow-up period was 9.6 （7-14 mo） mo. There was no local recurrenceat the follow-up points. Pneumothorax requiring pleural drainage was the main complication, which was observed in two of the seven patients （28.6%）. However, it improved with chest drainage tube, and the tube could be removed within 2-3 d. No other major complications were observed.CONCLUSION： CT-guided puncture is useful for the treatment of tumors located in the hepatic dome which are hardly detectable by US, even though pneumothorax sometimes may occur as a complication. In the cases with adhesion in the pleura for which artificial pleural effusion methods are not appropriate, CT-guided RFA is thus considered to be an alternative treatment for HCC located in the hepatic dome.
文摘Hepatic inflammatory pseudotumor （IPT） is a rare benign non-neoplastic lesion characterized by proliferating fibrous tissue infiltrated by inflammatory cells. The exact etiology of IPT remains unclear. Although the association of IPT with systemic inflammatory disorders has been well established, a specific relationship with cholangitis is distinctly rare. We report a case of spontaneous regression of hepatic IPT with primary biliary cirrhosis （PBC）. To date, only two cases of IPT with PBC have been reported. In our case, however, IPT developed during the course of improvement of cholangitis of PBC induced by effective treatment, differing from two previously reported cases. Our case indicates that the development of IPT does not also relate to the activity of cholangitis and/or hyper gamma-globulinemia, since our case was confirmed radiologically to be free of IPT when biliary enzymes and immunoglobulins were much higher than the corresponding values on admission. Comparison of our case with the two previously reported cases suggests that IPT occurring with PBC does not represent the same disease entity or be a bystander for PBC.
文摘AIM:To investigate whether endoscopic submucosal dissection(ESD) can be safely performed at small clinics,such as the Shirakawa Clinic.METHODS:One thousand forty-seven ESDs to treat gastrointestinal tumors were performed at the Shirakawa Clinic from April 2006 to March 2011.The efficacy,technical feasibility and associated complications of the procedures were assessed.The ESD procedures were performed by five endoscopists.Sedation was induced with propofol for esophagogastorduodenal ESD.RESULTS:One thousand forty-seven ESDs were performed to treat 64 patients with esophageal cancer(E),850 patients with gastric tumors(G:764 patients with cancer,82 patients with adenomas and four others),four patients with duodenal cancer(D) and 129 patients with colorectal tumors(C:94 patients with cancer,21 patients with adenomas and 14 others).The en bloc resection rate was 94.3%(E:96.9%,G:95.8%,D:100%,C:79.8%).The median operation time was 46 min(range:4-360 min) and the mean size of the resected specimens was 18 mm(range:2-150 mm).No mortal complications were observed in association with the ESD procedures.Perforation occurred in 12 cases(1.1%,E:1 case,G:9 cases,D:1 case,C:1 case) and postoperative bleeding occurred in 53 cases(5.1%,G:51 cases,D:1 case,C:1 case);however,no case required either emergency surgery or blood transfusion.All of the perforations and postperative bleedings were resolved by endoscopic clipping or hemostasis.The other problematic complication observed was pneumonia,which was treated with conservative therapy.CONCLUSION:ESD can be safely performed in a clinic with established therapeutic methods and medical services to address potential complications.
文摘Endoscopic submucosal dissection(ESD)has been proposed as the gold standard in the treatment of early gastric cancer because it facilitates a more accurate histological assessment and reduces the risk of tumor recurrence.However,the time course of ESD for large gastric tumors is frequently prolonged because of the tumor size and technical difficulties and typically requires higher doses of sedative and pain-controlling drugs.Sedative or anesthetic drugs such as midazolam or propofol are used during the procedure.Therapeutic endoscopy of early gastric cancers can often be performed with only moderate sedation.Compared with midazolam,propofol has a very fast onset of action,short plasma half-life and time to achieve sedation,faster time to recovery and discharge,and results in higher patient satisfaction.For overall success,maintaining safety and stability not only during the procedure but also subsequently in the recovery room and ward is necessary.In obese patients,it is recommended that the injected dose be based on a calculated standard weight.Cooperation between gastroenterologists,surgeons,and anesthesiologists is imperative for a successful ESD procedure.
文摘AIM： To evaluate the effect of three interventional treatments involving transvenous obliteration for the treatment of gastric varices, and to compare the efficacy and adverse effects of these methods, METHODS： From 1995 to 2004, 93 patients with gastric fundal varices underwent interventional radiologic embolotherapy at our hospital. Of the 93 patients, 75 were treated with the balloon-occluded retrograde transvenous obliteration （BRTO） procedure; 8 were with the percutaneous transhepatic obliteration （PTO） procedure; and 10 were with the combined BRTO and PTO therapy. A follow-up evaluation examined the rates of survival, recurrence and rebleeding of the gastric varices, worsening of esophageal varices and complications in each group. RESULTS： The BRTO, PTO, and combined therapy were technically successful in 81% （75/93）, 44% （8/18）, and 100% （10/10） patients, respectively. Recurrence of gastric varices was found in 3 patients in the BRTO group and in 3 patients in the PTO group. Rebleeding was observed in 1 patient in the BRTO group and in 1 patient in the PTO group. The 1- and 3-year survival rates were 98% and 87% in the patients without hepatocellular carcinoma （HCC） in the BRTO group, 100% and 100% in the PTO group, and 90% and 75% in the combined therapy group, respectively. CONCLUSION： Combined BRTO and PTO therapy may rescue cases with uncontrollable gastric fundal varices that remained even after treatment with BRTO and/or PTO, though there were limitations of our study, including retrospective nature and discrepancy in sample size between the BRTO, PTO and combined therapy groups.
文摘MK615, a compound extracted from the Japanese apricot "Prunus mume " has been reported to have in vitro anti-tumor activities against several cancer cell lines,including hepatocellular carcinoma(HCC). However, the clinical effects and feasibility of administering MK615for patients with HCC were unknown. We experienced a case with advanced HCC for which MK615 was effective against both lymph node and pulmonary metastases. A 60-year-old female underwent surgical resection of a 9 cm HCC in the right lobe. The pathological diagnosis was moderately differentiated HCC with vascular invasion. The HCC recurred in the liver 8 mo after the surgery. Radiofrequency ablation and transarterial infusion chemotherapy were performed, but the recurrence was not controlled. One year after the intrahepatic recurrence, pulmonary and lymph metastasis appeared.Sorafenib was administered, but was not effective.Then, MK615 was administered as a final alternative therapy after informed consent was obtained from the patient. Three months later, her alpha-fetoprotein level decrease and both the lymph node and pulmonary metastases decreased in size. The patient has survived for more than 17 mo after the MK615 administration, and was in good condition. Although further investigations are necessary to clarify its safety and efficacy in humans, MK615 may be useful for the treatment of HCC,without serious adverse effects.
文摘AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B,5-HT3 and 5-HT4 receptor antagonist administration.The force transducers were implanted on the serosal surfaces of the gastric antrum,terminal ileum,ileocecal sphincter and colon.Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state.The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed.RESULTS:5-HT2B,5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum.The 5-HT3 and 5-HT4 receptor antagonists inhibited phaseⅢof the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity.In the proximal colon,the inhibitory effect was dose dependent.Dose dependency,however,was not observed in the distal colon.The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.CONCLUSION:The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity.The5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.
文摘AIM To investigate the significance of heat shock protein 110(HSP110) in gastric cancer(GC) patients with peritoneal metastasis undergoing hyperthermochemotherapy.METHODS Primary GC patients(n = 14) with peritoneal metastasis or positive peritoneal lavage cytology who underwent distal or total gastrectomy between April 2000 and December 2011 were enrolled in this study. The patients underwent postoperative intraperitoneal hyperthermo-chemotherapy using a Thermotron RF-8 heating device two weeks after surgery. We analyzed nuclear HSP110 expression in surgically resected tumors using immunohistochemistry. Additionally, the effect of HSP110 suppression on hyptherthermochemosensitivity was assessed in vitro in the MKN45 GC cell line using the HSP inhibitor KNK437. RESULTS HSP110 immnohistochemical staining in 14 GC patients showed that five(35.7%) samples belonged to the low expression group, and nine(64.3%) samples belonged to the high expression group. Progression-free survival was significantly shorter in the HSP110 high-expression group than in the low-expression group(P = 0.0313). However, no significant relationships were identified between HSP110 expression and the clinicopathological characteristics of patients. Furthermore, high HSP110 expression was not an independent prognostic factor in GC patients with peritoneal metastasis(P = 0.0625). HSP110 expression in MKN45 cells was suppressed by KNK437 at the hyperthermic temperature of 43 ℃ in vitro. Comparison of MKN45 cell proliferation in the presence and absence of KNK437 at 43 ℃, revealed that proliferation was significantly decreased when HSP110 was inhibited by KNK437. Additionally, HSP110 suppression via HSP inhibitor treatment increased cellular sensitivity to hyperthermo-chemotherapy in vitro.CONCLUSION The expression of nuclear HSP110 in GC patients might be a new marker of chemosensitivity and a therapeutic target for patients who are tolerant to existing hyperthermo-chemotherapies.
文摘AIM： To define the clinical characteristics, and to as- sess the management of colonoscopic complications at a local clinic. METHODS： A retrospective review of the medical re- cords was performed for the patients with iatrogenic colon perforations after endoscopy at a local clinic be- tween April 2006 and December 2010. Data obtained from a tertiary hospital in the same region were also analyzed. The underlying conditions, clinical presenta- tions, perforation locations, treatment types （operative or conservative） and outcome data for patients at the local clinic and the tertiary hospital were compared. RESULTS： A total of 10 826 colonoscopies, and 2625 therapeutic procedures were performed at a local clinic and 32 148 colonoscopies, and 7787 therapeutic proce-dures were performed at the tertiary hospital. The clinic had no perforations during diagnostic colonoscopy and 8 （0.3%） perforations were determined to be related to therapeutic procedures. The perforation rates in each therapeutic procedure were 0.06% （1/1609） in polyp- ectomy, 0.2% （2/885） in endoscopic mucosal resection （EMR）, and 3.8% （5/131） in endoscopic submucosal dis- section （ESD）. Perforation rates for ESD were significantly higher than those for polypectomy or EMR （P 〈 0.01）. All of these patients were treated conservatively. On the oth- er hand, three （0.01%） perforation cases were observed among the 24 361 diagnostic procedures performed, and these cases were treated with surgery in a tertiary hospi- tal. Six perforations occurred with therapeutic endoscopy （perforation rate, 0.08%; 1 per 1298 procedures）. Perfo- ration rates for specific procedure types were 0.02% （1 per 5500） for polypectomy, 0.17% （1 per 561） for EMR, 2.3% （1 per 43） for ESD in the tertiary hospital. There were no differences in the perforation rates for each therapeutic procedure between the clinic and the tertiary hospital. The incidence of iatrogenic perforation requiring surgical treatment was quite low in both the clinic and the tertiary hospital. No procedure-related mortalities occurred. Performing closure with endoscopic clipping reduced the C-reactive protein （CRP） titers. The mean maximum CRP titer was 2.9：1：1.6 mg/dL with clipping and 9.7 ＋ 6.2 mg/dL without clipping, respectively （P 〈 0.05）. An operation is indicated in the presence of a large perforation, and in the setting of generalized peritonitis or ongoing sepsis. Although we did not experience such case in the clinic, patients with large perforations should be immediately transferred to a tertiary hospital. Good relationships between local clinics and nearby tertiary hospitals should therefore be maintained. CONCLUSION： It was therefore found to be possible to perform endoscopic treatment at a local clinic when sufficient back up was available at a nearby tertiary hospital.
