AIM:To investigate the association of procalcitonin(PCT)with ulcerative colitis(UC)activity.METHODS:Serum PCT levels,C-reactive protein(CRP)levels,the erythrocyte sedimentation rate,and the white blood cell count were...AIM:To investigate the association of procalcitonin(PCT)with ulcerative colitis(UC)activity.METHODS:Serum PCT levels,C-reactive protein(CRP)levels,the erythrocyte sedimentation rate,and the white blood cell count were analyzed in 18 patients with UC and 11 healthy volunteers.Serum PCT levels were analyzed by an electrochemiluminescence immunoassay.Severity assessments were based on Truelove and Witts’severity index.Correlation of serum PCT and CRP levels with UC activity was examined.Moreover,we assessed serum PCT and CRP levels in patients with a Mayo endoscopic subscore.RESULTS:Serum PCT levels in severe UC patients(n=7)(0.096±0.034 ng/mL)were significantly higher than in mild-to-moderate UC patients(n=11)(0.033±0.012 ng/mL)and healthy volunteers(n=11)(0.035±0.005 ng/mL)(P=0.0005 and P<0.0001,respectively).In addition,there was no difference in serum PCT levels between mild-to-moderate UC patients and healthy volunteers.Interestingly,patients with a Mayo endoscopic subscore of 3 points displayed significantly increased levels of serum PCT(0.075±0.043 ng/mL)compared with patients with a subscore of 2 points(0.03±0.011 ng/mL)(P=0.0302).Moreover,CRP levels in patients with severe UC or a Mayo endoscopic subscore of 3 points were not significantly higher than in patients with mild-to-moderate UC or a Mayo endoscopic subscore of 3 points.CONCLUSION:Serum PCT levels were significantly correlated with UC activity.展开更多
The incidence of colorectal cancer(CRC)is on the rise,and the prognosis for patients with recurrent or metastatic disease is extremely poor.Although chemotherapy and radiation therapy can improve survival rates,it is ...The incidence of colorectal cancer(CRC)is on the rise,and the prognosis for patients with recurrent or metastatic disease is extremely poor.Although chemotherapy and radiation therapy can improve survival rates,it is imperative to integrate alternative strategies such as immunotherapy to improve outcomes for patients with advanced CRC.In this review,we will discuss the effect of immunotherapy for inducing cytotoxic T lymphocytes and the major immunotherapeutic approaches for CRC that are currently in clinical trials,including peptide vaccines,dendritic cell-based cancer vaccines,whole tumor cell vaccines,viral vector-based cancer vaccines,adoptive cell transfer therapy,antibody-based cancer immunotherapy,and cytokine therapy.The possibility of combination therapies will also be discussed along with the challenges presented by tumor escape mechanisms.展开更多
AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaettn, has been clinically used for vascular diseases such as occlusive v...AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaettn, has been clinically used for vascular diseases such as occlusive vasculitis, coronary diseases, atherosclerosis, and cerebral infarction. The main component, Salviae Miltiorrhizae, has been reported to prevent cerebral and intestinal reperfusion injury. However, little is known about the effect of CP on hepatic microcirculation. Thus, this study aimed to determine whether CP could affect hepatic microvascular dysfunction elicited by gut ischemia/ reperfusion (I/R) in rats fed ethanol chronically. METHODS: Male Wistar rats were pair-fed with a liquid diet containing ethanol or isocaloric control diet for 6 wk. After laparotomy, one lobe of the liver was examined through an inverted intravital microscope. The rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Rhodamine-6G-labeled leukocytes in the sinusoids were observed 90 min after the onset of superior mesenteric artery occlusion. Plasma tumor necrosis factor (TNF)-α and endotoxin levels were measured 1 h after the onset of reperfusion. Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, CP (0.8 g/kg, intragastrically) was administered 1 and 24 h before the onset of ischemia. RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF-α and endotoxin levels and plasma ALT activities. These changes were mitigated by pretreatment with CP. In ethanol-fed rats, the gut I/R-induced increases in the number of stationary leukocytes, plasma endotoxin levels and ALT activities were enhanced. Pretreatment with CP attenuated the enhancement of gut I/R-induced responses by chronic ethanol consumption. CONCLUSION: These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury. A reduction of inflammatory responses such as TNF-α production via reduction of blood endotoxin levels appears to be involved in the mechanisms. Chronic ethanol consumption enhances gut I/R-induced hepatic microvascular and hepatocellular injury. CP also attenuates an enhancement of gut I/R-induced responses by chronic ethanol consumption via the reduction of blood endotoxin levels.展开更多
The incidence of pancreatic ductal adenocarcinoma(PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-b...The incidence of pancreatic ductal adenocarcinoma(PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients.展开更多
Colorectal cancer(CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the pro...Colorectal cancer(CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients.展开更多
AIM:To determine whether Saiko-keishi-to(TJ-10),a Japanese herbal medicine,could protect liver injury induced by gut ischemia/reperfusion(I/R),and to investigate the role of NO. METHODS:Male Wistar rats were exposed t...AIM:To determine whether Saiko-keishi-to(TJ-10),a Japanese herbal medicine,could protect liver injury induced by gut ischemia/reperfusion(I/R),and to investigate the role of NO. METHODS:Male Wistar rats were exposed to 30-min gut isohemia followed by 60 min of reperfusion.Intravital microscopy was used to monitor leukocyte recruitment.Plasma tumor necrosis factor(TNF)levels and alanine aminotransferase (ALT)activities were measured.TJ-10 1 g/(kg.d)was intragastrically administered to rats for 7 d.A NO synthase inhibitor was administered. RESULTS:In control rats,gut I/R elicited increases in the number of stationary leukocytes,and plasma TNF levels and ALT activities were mitigated by pretreatment with TJ-10.Pretreatment with the NO synthase inhibitor diminished the protective effects of TJ-10 on leukostasis in the liver,and the increase of plasma TNF levels and ALT activities.Pretreatment with TJ-10 increased plasma nitrite/nitrate levels. CONCLUSION:TJ-10 attenuates the gut I/R-induced hepatic microvascular dysfunction and sequential hepatocellular injury via enhancement of NO production.展开更多
AIM: To investigate the association of plasma levels of interleukin(IL)-6 and-8 with Wilms' tumor 1(WT1)-specific immune responses and clinical outcomes in patients with pancreatic ductal adenocarcinoma(PDA) treat...AIM: To investigate the association of plasma levels of interleukin(IL)-6 and-8 with Wilms' tumor 1(WT1)-specific immune responses and clinical outcomes in patients with pancreatic ductal adenocarcinoma(PDA) treated with dendritic cells(DCs) pulsed with three types of major histocompatibility complex classⅠand Ⅱ-restricted WT1 peptides combined with chemotherapy.METHODS: During the entire treatment period, plasma levels of IL-6 and-8 were analyzed by ELISA. The induction of WT1-specific immune responses was assessed using the WT1 peptide-specific delayed-type hypersensitivity(DTH) test.RESULTS: Three of 7 patients displayed strong WT1-DTH reactions throughout long-term vaccination with significantly decreased levels of IL-6/-8 after vaccinations compared with the levels prior to treatment. Moreover, overall survival(OS) was significantly longer in PDA patients with low plasma IL-6 levels(< 2 pg/m L) after 5 vaccinations than in patients with high plasma IL-6 levels(≥ 2 pg/m L)(P = 0.025). After disease progression, WT1-DTH reactions decreased severely and were ultimately negative at the terminal stage of cancer. The decreased levels of IL-6/-8 observed throughout long-term vaccination were associated with WT1-specific DTH reactions and long-term OS.CONCLUSION: Prolonged low levels of plasma IL-6/-8 in PDA patients may be a prognostic marker for the clinical outcomes of chemoimmunotherapy.展开更多
A case of a patient with bilateral endophthalmitis and vertebral infection is presented here. The case presented with fever, general malaise, reduced vision and back pain for at least two weeks. Diagnosis was establis...A case of a patient with bilateral endophthalmitis and vertebral infection is presented here. The case presented with fever, general malaise, reduced vision and back pain for at least two weeks. Diagnosis was established by positive blood cultures together with ophthalmology review and radiological findings. Streptococcus dysgalactiae subspecies equisimilis was isolated from blood cultures. This case demonstrates the risks for older patients of developing invasive disease upon exposure to Streptococcus dysgalactiae, even if underlying diseases are absent.展开更多
基金Supported by Grants-in-Aid for Scientific Research (C) from the Ministry of EducationCulture+2 种基金SportsScience and Technology of JapanNo.23501289
文摘AIM:To investigate the association of procalcitonin(PCT)with ulcerative colitis(UC)activity.METHODS:Serum PCT levels,C-reactive protein(CRP)levels,the erythrocyte sedimentation rate,and the white blood cell count were analyzed in 18 patients with UC and 11 healthy volunteers.Serum PCT levels were analyzed by an electrochemiluminescence immunoassay.Severity assessments were based on Truelove and Witts’severity index.Correlation of serum PCT and CRP levels with UC activity was examined.Moreover,we assessed serum PCT and CRP levels in patients with a Mayo endoscopic subscore.RESULTS:Serum PCT levels in severe UC patients(n=7)(0.096±0.034 ng/mL)were significantly higher than in mild-to-moderate UC patients(n=11)(0.033±0.012 ng/mL)and healthy volunteers(n=11)(0.035±0.005 ng/mL)(P=0.0005 and P<0.0001,respectively).In addition,there was no difference in serum PCT levels between mild-to-moderate UC patients and healthy volunteers.Interestingly,patients with a Mayo endoscopic subscore of 3 points displayed significantly increased levels of serum PCT(0.075±0.043 ng/mL)compared with patients with a subscore of 2 points(0.03±0.011 ng/mL)(P=0.0302).Moreover,CRP levels in patients with severe UC or a Mayo endoscopic subscore of 3 points were not significantly higher than in patients with mild-to-moderate UC or a Mayo endoscopic subscore of 3 points.CONCLUSION:Serum PCT levels were significantly correlated with UC activity.
基金Supported by Grants in Aid for Scientific Research(C)from the Japanese Ministry of Education,Culture,Sports,Science and Technology
文摘The incidence of colorectal cancer(CRC)is on the rise,and the prognosis for patients with recurrent or metastatic disease is extremely poor.Although chemotherapy and radiation therapy can improve survival rates,it is imperative to integrate alternative strategies such as immunotherapy to improve outcomes for patients with advanced CRC.In this review,we will discuss the effect of immunotherapy for inducing cytotoxic T lymphocytes and the major immunotherapeutic approaches for CRC that are currently in clinical trials,including peptide vaccines,dendritic cell-based cancer vaccines,whole tumor cell vaccines,viral vector-based cancer vaccines,adoptive cell transfer therapy,antibody-based cancer immunotherapy,and cytokine therapy.The possibility of combination therapies will also be discussed along with the challenges presented by tumor escape mechanisms.
文摘AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaettn, has been clinically used for vascular diseases such as occlusive vasculitis, coronary diseases, atherosclerosis, and cerebral infarction. The main component, Salviae Miltiorrhizae, has been reported to prevent cerebral and intestinal reperfusion injury. However, little is known about the effect of CP on hepatic microcirculation. Thus, this study aimed to determine whether CP could affect hepatic microvascular dysfunction elicited by gut ischemia/ reperfusion (I/R) in rats fed ethanol chronically. METHODS: Male Wistar rats were pair-fed with a liquid diet containing ethanol or isocaloric control diet for 6 wk. After laparotomy, one lobe of the liver was examined through an inverted intravital microscope. The rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Rhodamine-6G-labeled leukocytes in the sinusoids were observed 90 min after the onset of superior mesenteric artery occlusion. Plasma tumor necrosis factor (TNF)-α and endotoxin levels were measured 1 h after the onset of reperfusion. Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, CP (0.8 g/kg, intragastrically) was administered 1 and 24 h before the onset of ischemia. RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF-α and endotoxin levels and plasma ALT activities. These changes were mitigated by pretreatment with CP. In ethanol-fed rats, the gut I/R-induced increases in the number of stationary leukocytes, plasma endotoxin levels and ALT activities were enhanced. Pretreatment with CP attenuated the enhancement of gut I/R-induced responses by chronic ethanol consumption. CONCLUSION: These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury. A reduction of inflammatory responses such as TNF-α production via reduction of blood endotoxin levels appears to be involved in the mechanisms. Chronic ethanol consumption enhances gut I/R-induced hepatic microvascular and hepatocellular injury. CP also attenuates an enhancement of gut I/R-induced responses by chronic ethanol consumption via the reduction of blood endotoxin levels.
文摘The incidence of pancreatic ductal adenocarcinoma(PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients.
基金Supported by Grants in Aid for Scientific Research (C) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology.
文摘Colorectal cancer(CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients.
基金Supported by Grants-in-Aid for Scientific Research(C)from the Ministry of Education,Culture,Sports,Science,and Tech-nology of Japanthe Foundation for the Promotion of Can-cer Research and Mitsui Life Social Welfare Foundation
文摘AIM: To examine whether commensal bacteria are a contributing cause of stress-related mucosal inflammation.
文摘AIM:To determine whether Saiko-keishi-to(TJ-10),a Japanese herbal medicine,could protect liver injury induced by gut ischemia/reperfusion(I/R),and to investigate the role of NO. METHODS:Male Wistar rats were exposed to 30-min gut isohemia followed by 60 min of reperfusion.Intravital microscopy was used to monitor leukocyte recruitment.Plasma tumor necrosis factor(TNF)levels and alanine aminotransferase (ALT)activities were measured.TJ-10 1 g/(kg.d)was intragastrically administered to rats for 7 d.A NO synthase inhibitor was administered. RESULTS:In control rats,gut I/R elicited increases in the number of stationary leukocytes,and plasma TNF levels and ALT activities were mitigated by pretreatment with TJ-10.Pretreatment with the NO synthase inhibitor diminished the protective effects of TJ-10 on leukostasis in the liver,and the increase of plasma TNF levels and ALT activities.Pretreatment with TJ-10 increased plasma nitrite/nitrate levels. CONCLUSION:TJ-10 attenuates the gut I/R-induced hepatic microvascular dysfunction and sequential hepatocellular injury via enhancement of NO production.
基金Grants-in-Aid for Scientific Research(C)from the Ministry of Education,Culture,Sports,Science and Technology of Japan
文摘AIM: To investigate the association of plasma levels of interleukin(IL)-6 and-8 with Wilms' tumor 1(WT1)-specific immune responses and clinical outcomes in patients with pancreatic ductal adenocarcinoma(PDA) treated with dendritic cells(DCs) pulsed with three types of major histocompatibility complex classⅠand Ⅱ-restricted WT1 peptides combined with chemotherapy.METHODS: During the entire treatment period, plasma levels of IL-6 and-8 were analyzed by ELISA. The induction of WT1-specific immune responses was assessed using the WT1 peptide-specific delayed-type hypersensitivity(DTH) test.RESULTS: Three of 7 patients displayed strong WT1-DTH reactions throughout long-term vaccination with significantly decreased levels of IL-6/-8 after vaccinations compared with the levels prior to treatment. Moreover, overall survival(OS) was significantly longer in PDA patients with low plasma IL-6 levels(< 2 pg/m L) after 5 vaccinations than in patients with high plasma IL-6 levels(≥ 2 pg/m L)(P = 0.025). After disease progression, WT1-DTH reactions decreased severely and were ultimately negative at the terminal stage of cancer. The decreased levels of IL-6/-8 observed throughout long-term vaccination were associated with WT1-specific DTH reactions and long-term OS.CONCLUSION: Prolonged low levels of plasma IL-6/-8 in PDA patients may be a prognostic marker for the clinical outcomes of chemoimmunotherapy.
文摘A case of a patient with bilateral endophthalmitis and vertebral infection is presented here. The case presented with fever, general malaise, reduced vision and back pain for at least two weeks. Diagnosis was established by positive blood cultures together with ophthalmology review and radiological findings. Streptococcus dysgalactiae subspecies equisimilis was isolated from blood cultures. This case demonstrates the risks for older patients of developing invasive disease upon exposure to Streptococcus dysgalactiae, even if underlying diseases are absent.
