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
Background Liver transplantation is the most effective treatment for end-stage liver diseases; however, infections after transplantation can seriously affect the patient＇s health. The aim of this research was to inve...Background Liver transplantation is the most effective treatment for end-stage liver diseases; however, infections after transplantation can seriously affect the patient＇s health. The aim of this research was to investigate the diagnosis and treatment of fungal infection following liver transplantation.展开更多
AIM: To evaluate long-term prognosis following cyclosporine treatment by examining the rate of surgery avoidance among cyclosporine responders.METHODS: We retrospectively reviewed clinical records for 29 patients diag...AIM: To evaluate long-term prognosis following cyclosporine treatment by examining the rate of surgery avoidance among cyclosporine responders.METHODS: We retrospectively reviewed clinical records for 29 patients diagnosed with severe steroid-refractory ulcerative colitis in our hospital from August 1997 to August 2008 and treated with cyclosporine by continuous intravenous infusion.All patients were treated with intravenous corticosteroids for more than 5 d prior to cyclosporine therapy.Administration was continued for up to 21 d under serum monitoring to maintain cyclosporine levels between 400 and 600 ng/mL.Clinical activity was assessed before and after cyclosporine therapy using the clinical activity index score,with a reduction of ≥ 5 considered to indicate a response.Among responders,we defined cases not requiring surgery for more than 5 years as exhibiting long-term efficacy of cyclosporine.Factors considered to be possibly predictive of long-term efficacy of cyclosporine were sex,age,disease duration,clinical activity index score,C-reactive protein level,hemoglobin level,disease extent,endoscopic findings,and clinical course.RESULTS: Cyclosporine was not discontinued due to side effects in any patient.Nineteen(65.5%) of 29 patients were considered responders.A statistically significant(P = 0.004) inverseas sociation wa s observed between an endoscopic finding of "mucosal bleeding" and responsive cases.Fifteen(9 males,6 females) of these 19 patients were followed for 5 years or more,of whom 9(60%) exhibited long-termefficacy of cyclosporine.Of the 10 non-responders,9(90%) underwent surgery within 6 mo of cyclosporine therapy.None of the following factors had a significant impact on the long-term efficacy of cyclosporine: sex,age,duration of disease,clinical activity index score,C-reactive protein level,hemoglobin level,extent of disease,endoscopic findings,or clinical course.In contrast,a significant association was observed for maintenance therapy with azathioprine after cyclosporine therapy(P = 0.0014展开更多
Systemic chemotherapy has enabled prolongation of survival in patients with stage IV colorectal cancer. This has subsequently increased the relative significance of local therapy for patients with oligometastases beca...Systemic chemotherapy has enabled prolongation of survival in patients with stage IV colorectal cancer. This has subsequently increased the relative significance of local therapy for patients with oligometastases because they can be cured by removal of oligometastatic lesions. One of the most frequently reported tumor histologies for oligometastases is colorectal cancer. Resection is the standard therapy in most settings of oligometastases. Recently, studies have shown that stereotactic body radiotherapy (SBRT) may become a treatment option that provides high local control with minimal morbidity. Two-year local control rates following SBRT for hepatic and pulmonary oligometastases are almost over 80% and are even higher for patients treated with high-dose regimens. The indications of SBRT for other metastatic sites or conditions include isolated lymph nodes, spinal and adrenal metastasis, and post-surgical pelvic recurrence. Many retrospective studies have indicated that SBRT for various lesions results in good outcomes with low morbidity, both in the curative and palliative setting. However, few reports with a high level of evidence have indicated the efficacy of SBRT compared to standard therapy. Hereafter, the optimal indication of SBRT needs to be prospectively investigated to obtain convincing evidence.展开更多
Convincing evidence indicates that the existence of cancer stem cells （CSCs） within malignant tumors is mostly responsible for the failure of chemotherapy. Therefore, instead of merely targeting bulk cancer cells, s...Convincing evidence indicates that the existence of cancer stem cells （CSCs） within malignant tumors is mostly responsible for the failure of chemotherapy. Therefore, instead of merely targeting bulk cancer cells, simultaneous elimin- ation of both CSCs and bulk cancer cells is necessary to improve therapeutic outcomes. Herein, we designed cationic-lipid-assisted nanopartides DTXLNPsRNA for simultaneous encapsulation of the conventional chemotherapeutic agent docetaxel （DTXL） and small interfering RNA （siRNA） targeting BMI-1 （siBMI-1）. We confirmed that nanopartides vrxLNPsiBMI-l effectively deliver both therapeutic agents into CSCs and bulk cancer cells. The bulk cancer cells were effectively killed by the DTXL encapsulated in DVXL NPsiBMI-1. In breast CSCs, BMI-1 expression was significantly downregulated by DVXLNpsiBMI-1; consequently, the sternness was reduced and chemosensitivity of CSCs to DTXL was enhanced, resulting in the elimination of CSCs. Therefore, via DTXLNPsiBMI-1, the combination of siBMI-1 and DTXL completely inhibited tumor growth and prevented a relapse by synergistic kiUing of CSCs and bulk cancer cells in a murine model of an MDA-MB-231 orthotropic tumor.展开更多
Chemodynamic therapy(CDT) is a promising therapeutic approach for in situ cancer treatment, but it is still hindered by inefficient single-modality treatment and the weak targeted delivery of reagents into mitochondri...Chemodynamic therapy(CDT) is a promising therapeutic approach for in situ cancer treatment, but it is still hindered by inefficient single-modality treatment and the weak targeted delivery of reagents into mitochondria(the main site of intracellular ROS production). Herein, to obtain a multimodal strategy,peptide-assembled si RNA nanomicelles were prepared to confine ultrasmall MnOxin small silica cages(silicages), which is convenient for synergistic chemical and gene-regulated cancer therapy. Given the free energy and versatility of small silicages, as well as the excellent Fenton-like activity of ultrasmall MnOx,MnOx-inside-loaded silicages(10 nm) were prepared for CDT delivery to mitochondria. Subsequently, to obtain a synergistic CDT and gene silencing treatment, the peptide-mediated assembly of si RNA and MnOx-loaded silicages were employed to obtain silicage@MnOx-si RNA nanomicelles(SMS NMs). After multiple modifications, sequential cancer cell-targeted delivery, GSH-controlled reagent release of si RNA and mitochondria-targeted delivery of MnOx-loaded silicages were successfully achieved. Finally, by both in vitro and in vivo experiments, SMS NMs were confirmed to be effective for synergistic chemical and gene-regulated cancer therapy. Our findings expand the applications of silicages and initiate the development of multimodal CDT.展开更多
AIM To examine the influence of night duty(ND) on endoscopic therapy for biliary duct stones.METHODS The subjects consisted of 133 patients who received initial endoscopic therapy for biliary duct stones performed by ...AIM To examine the influence of night duty(ND) on endoscopic therapy for biliary duct stones.METHODS The subjects consisted of 133 patients who received initial endoscopic therapy for biliary duct stones performed by eight endoscopists after they had been on(ND group, n = 34 patients) or not [day duty(DD) group, n = 99 patients]. Patient characteristics(age, gender, history of abdominal surgery, transverse diameter of the largest stone, number of stones), years of experience of the endoscopists, endoscopic procedures [sphincterotomy, papillary balloon dilation(EPBD), papillary large balloon dilation(EPLBD)], and outcomes of initial endoscopy(procedure time; rate of stone removal by the first endoscopist; proceduresuccess rate by the first endoscopist: removal of stones or endoscopic retrograde biliary drainage; rate of final stone removal; final procedure success rate; complications; hospitalization after the procedure) were compared retrospectively between the two groups. History of abdominal surgery and treatment outcomes were also compared between the groups for each of the four endoscopists who performed most of the procedures in the ND group.RESULTS There were no significant differences regarding the number of treatments performed by each endoscopist or the years of experience between the ND and DD groups. The frequency of endoscopic retrograde cholangiopancreatography procedures did not differ significantly between the groups. There were also no significant differences regarding patient characteristics: age, gender, history of abdominal surgery(ND 7: Billroth II 4, R-Y 3; DD 18: double tract reconstruction 1, Billroth I 3, Billroth II 6, R-Y 7, duodenoduodenostomy for annular pancreas 1), transverse diameter of largest stone, and number of stones between the two groups. Among the treatment procedures, the endoscopic s p h i n c t e r o t o m y a n d E P B D r a t e s d i d n o t d i f f e r significantly between the groups. However, EPLBD was performed more frequently in the ND group [47.1%(16/34) v s 19.2%展开更多
Gastric carcinosarcomas are rare morphologically biphasic tumors, consisting of carcinoma and sarcoma components, with a poor clinical course.Here we report the case of a 70-year-old man with advanced Borrmann type Ⅲ...Gastric carcinosarcomas are rare morphologically biphasic tumors, consisting of carcinoma and sarcoma components, with a poor clinical course.Here we report the case of a 70-year-old man with advanced Borrmann type Ⅲ carcinosarcoma arising from the upper body of the stomach with extensive lymph node metastasis who underwent a total, but palliative, gastrectomy.Histology showed the tumor consisted of a biphasic structure of tubular adenocarcinoma and spindle cellsarcoma.Immunohistochemistry revealed sarcoma cells expressing c-kit(CD117) and CD34, which are criteria for gastrointestinal stromal tumors.Nine months after the surgical operation, tumor metastases had extended to the hepatohilar, retroperitoneal and mediastinal lymph nodes.Radiation therapy of 50 Gy markedly decreased the size of each of these nodes and reduced the risk of respiratory complications and jaundice.However, the patient died of respiratory failure due to bronchopneumonia with multiple lung metastases 22 mo after resection.Autopsy revealed severe necrosis in most of the lymph nodes with tumor metastases.Radiation therapy combined with gastrectomy should be considered to improve survival in patients with gastric carcinosarcomas that express c-kit.展开更多
It has been approximately six and one-half yearssince the first patient was enrolled in a gene therapyclinical trial. Since that important begining, this typeof genetic intervention has grown into a worldwideinvestiga...It has been approximately six and one-half yearssince the first patient was enrolled in a gene therapyclinical trial. Since that important begining, this typeof genetic intervention has grown into a worldwideinvestigative activity involving about 2100 patients asof December 1996. Although it was initially展开更多
OBJECTIVES The Old Herborn University Seminar presents a series of seminars onthe microbial ecology of the intestinal tract, related areas, epithelial and other surfaces and its relevance to the medical field. The ser...OBJECTIVES The Old Herborn University Seminar presents a series of seminars onthe microbial ecology of the intestinal tract, related areas, epithelial and other surfaces and its relevance to the medical field. The series of seminars will provide successive coverage of thedeveloping knowledge of the interaction between indigenous microflora and various host organ systems in hu-展开更多
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Background Liver transplantation is the most effective treatment for end-stage liver diseases; however, infections after transplantation can seriously affect the patient＇s health. The aim of this research was to investigate the diagnosis and treatment of fungal infection following liver transplantation.
文摘AIM: To evaluate long-term prognosis following cyclosporine treatment by examining the rate of surgery avoidance among cyclosporine responders.METHODS: We retrospectively reviewed clinical records for 29 patients diagnosed with severe steroid-refractory ulcerative colitis in our hospital from August 1997 to August 2008 and treated with cyclosporine by continuous intravenous infusion.All patients were treated with intravenous corticosteroids for more than 5 d prior to cyclosporine therapy.Administration was continued for up to 21 d under serum monitoring to maintain cyclosporine levels between 400 and 600 ng/mL.Clinical activity was assessed before and after cyclosporine therapy using the clinical activity index score,with a reduction of ≥ 5 considered to indicate a response.Among responders,we defined cases not requiring surgery for more than 5 years as exhibiting long-term efficacy of cyclosporine.Factors considered to be possibly predictive of long-term efficacy of cyclosporine were sex,age,disease duration,clinical activity index score,C-reactive protein level,hemoglobin level,disease extent,endoscopic findings,and clinical course.RESULTS: Cyclosporine was not discontinued due to side effects in any patient.Nineteen(65.5%) of 29 patients were considered responders.A statistically significant(P = 0.004) inverseas sociation wa s observed between an endoscopic finding of "mucosal bleeding" and responsive cases.Fifteen(9 males,6 females) of these 19 patients were followed for 5 years or more,of whom 9(60%) exhibited long-termefficacy of cyclosporine.Of the 10 non-responders,9(90%) underwent surgery within 6 mo of cyclosporine therapy.None of the following factors had a significant impact on the long-term efficacy of cyclosporine: sex,age,duration of disease,clinical activity index score,C-reactive protein level,hemoglobin level,extent of disease,endoscopic findings,or clinical course.In contrast,a significant association was observed for maintenance therapy with azathioprine after cyclosporine therapy(P = 0.0014
文摘Systemic chemotherapy has enabled prolongation of survival in patients with stage IV colorectal cancer. This has subsequently increased the relative significance of local therapy for patients with oligometastases because they can be cured by removal of oligometastatic lesions. One of the most frequently reported tumor histologies for oligometastases is colorectal cancer. Resection is the standard therapy in most settings of oligometastases. Recently, studies have shown that stereotactic body radiotherapy (SBRT) may become a treatment option that provides high local control with minimal morbidity. Two-year local control rates following SBRT for hepatic and pulmonary oligometastases are almost over 80% and are even higher for patients treated with high-dose regimens. The indications of SBRT for other metastatic sites or conditions include isolated lymph nodes, spinal and adrenal metastasis, and post-surgical pelvic recurrence. Many retrospective studies have indicated that SBRT for various lesions results in good outcomes with low morbidity, both in the curative and palliative setting. However, few reports with a high level of evidence have indicated the efficacy of SBRT compared to standard therapy. Hereafter, the optimal indication of SBRT needs to be prospectively investigated to obtain convincing evidence.
文摘Convincing evidence indicates that the existence of cancer stem cells （CSCs） within malignant tumors is mostly responsible for the failure of chemotherapy. Therefore, instead of merely targeting bulk cancer cells, simultaneous elimin- ation of both CSCs and bulk cancer cells is necessary to improve therapeutic outcomes. Herein, we designed cationic-lipid-assisted nanopartides DTXLNPsRNA for simultaneous encapsulation of the conventional chemotherapeutic agent docetaxel （DTXL） and small interfering RNA （siRNA） targeting BMI-1 （siBMI-1）. We confirmed that nanopartides vrxLNPsiBMI-l effectively deliver both therapeutic agents into CSCs and bulk cancer cells. The bulk cancer cells were effectively killed by the DTXL encapsulated in DVXL NPsiBMI-1. In breast CSCs, BMI-1 expression was significantly downregulated by DVXLNpsiBMI-1; consequently, the sternness was reduced and chemosensitivity of CSCs to DTXL was enhanced, resulting in the elimination of CSCs. Therefore, via DTXLNPsiBMI-1, the combination of siBMI-1 and DTXL completely inhibited tumor growth and prevented a relapse by synergistic kiUing of CSCs and bulk cancer cells in a murine model of an MDA-MB-231 orthotropic tumor.
基金the financial support provided by the National Natural Science Foundation of China (NNSFC, No. 21874012)the National Key Research and Development Program of China (No.2019YFC1805600)the financial support provided by NNSFC (No. 21974010)。
文摘Chemodynamic therapy(CDT) is a promising therapeutic approach for in situ cancer treatment, but it is still hindered by inefficient single-modality treatment and the weak targeted delivery of reagents into mitochondria(the main site of intracellular ROS production). Herein, to obtain a multimodal strategy,peptide-assembled si RNA nanomicelles were prepared to confine ultrasmall MnOxin small silica cages(silicages), which is convenient for synergistic chemical and gene-regulated cancer therapy. Given the free energy and versatility of small silicages, as well as the excellent Fenton-like activity of ultrasmall MnOx,MnOx-inside-loaded silicages(10 nm) were prepared for CDT delivery to mitochondria. Subsequently, to obtain a synergistic CDT and gene silencing treatment, the peptide-mediated assembly of si RNA and MnOx-loaded silicages were employed to obtain silicage@MnOx-si RNA nanomicelles(SMS NMs). After multiple modifications, sequential cancer cell-targeted delivery, GSH-controlled reagent release of si RNA and mitochondria-targeted delivery of MnOx-loaded silicages were successfully achieved. Finally, by both in vitro and in vivo experiments, SMS NMs were confirmed to be effective for synergistic chemical and gene-regulated cancer therapy. Our findings expand the applications of silicages and initiate the development of multimodal CDT.
文摘AIM To examine the influence of night duty(ND) on endoscopic therapy for biliary duct stones.METHODS The subjects consisted of 133 patients who received initial endoscopic therapy for biliary duct stones performed by eight endoscopists after they had been on(ND group, n = 34 patients) or not [day duty(DD) group, n = 99 patients]. Patient characteristics(age, gender, history of abdominal surgery, transverse diameter of the largest stone, number of stones), years of experience of the endoscopists, endoscopic procedures [sphincterotomy, papillary balloon dilation(EPBD), papillary large balloon dilation(EPLBD)], and outcomes of initial endoscopy(procedure time; rate of stone removal by the first endoscopist; proceduresuccess rate by the first endoscopist: removal of stones or endoscopic retrograde biliary drainage; rate of final stone removal; final procedure success rate; complications; hospitalization after the procedure) were compared retrospectively between the two groups. History of abdominal surgery and treatment outcomes were also compared between the groups for each of the four endoscopists who performed most of the procedures in the ND group.RESULTS There were no significant differences regarding the number of treatments performed by each endoscopist or the years of experience between the ND and DD groups. The frequency of endoscopic retrograde cholangiopancreatography procedures did not differ significantly between the groups. There were also no significant differences regarding patient characteristics: age, gender, history of abdominal surgery(ND 7: Billroth II 4, R-Y 3; DD 18: double tract reconstruction 1, Billroth I 3, Billroth II 6, R-Y 7, duodenoduodenostomy for annular pancreas 1), transverse diameter of largest stone, and number of stones between the two groups. Among the treatment procedures, the endoscopic s p h i n c t e r o t o m y a n d E P B D r a t e s d i d n o t d i f f e r significantly between the groups. However, EPLBD was performed more frequently in the ND group [47.1%(16/34) v s 19.2%
文摘Gastric carcinosarcomas are rare morphologically biphasic tumors, consisting of carcinoma and sarcoma components, with a poor clinical course.Here we report the case of a 70-year-old man with advanced Borrmann type Ⅲ carcinosarcoma arising from the upper body of the stomach with extensive lymph node metastasis who underwent a total, but palliative, gastrectomy.Histology showed the tumor consisted of a biphasic structure of tubular adenocarcinoma and spindle cellsarcoma.Immunohistochemistry revealed sarcoma cells expressing c-kit(CD117) and CD34, which are criteria for gastrointestinal stromal tumors.Nine months after the surgical operation, tumor metastases had extended to the hepatohilar, retroperitoneal and mediastinal lymph nodes.Radiation therapy of 50 Gy markedly decreased the size of each of these nodes and reduced the risk of respiratory complications and jaundice.However, the patient died of respiratory failure due to bronchopneumonia with multiple lung metastases 22 mo after resection.Autopsy revealed severe necrosis in most of the lymph nodes with tumor metastases.Radiation therapy combined with gastrectomy should be considered to improve survival in patients with gastric carcinosarcomas that express c-kit.
文摘It has been approximately six and one-half yearssince the first patient was enrolled in a gene therapyclinical trial. Since that important begining, this typeof genetic intervention has grown into a worldwideinvestigative activity involving about 2100 patients asof December 1996. Although it was initially
文摘OBJECTIVES The Old Herborn University Seminar presents a series of seminars onthe microbial ecology of the intestinal tract, related areas, epithelial and other surfaces and its relevance to the medical field. The series of seminars will provide successive coverage of thedeveloping knowledge of the interaction between indigenous microflora and various host organ systems in hu-
