The number of patients with nonalcoholic fatty liver diseases(NAFLD) including nonalcoholic steatohepatitis(NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma(HCC) and is one of the most se...The number of patients with nonalcoholic fatty liver diseases(NAFLD) including nonalcoholic steatohepatitis(NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma(HCC) and is one of the most serious health problems in the world. The mechanism through which NASH progresses is still largely unknown. Activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD/NASH. Apoptotic hepatocytes stimulate immune cells and hepatic stellate cells toward the progression of fibrosis in the liver through the production of inflammasomes and cytokines. Abnormalities in glucose and lipid metabolism as well as microbiota accelerate these processes. The production of reactive oxygen species, oxidative stress, and endoplasmic reticulum stress is also involved. Cell death, including apoptosis, seems very important in the progression of NAFLD and NASH. Recently, inhibitors of apoptosis have been developed as drugs for the treatment of NASH and may prevent cirrhosis and HCC. Increased hepatocyte apoptosis may distinguish NASH from NAFLD, and the improvement of apoptosis could play a role in controlling the development of NASH. In this review, the association between apoptosis and NAFLD/NASH are discussed. This review could provide their knowledge, which plays a role in seeing the patients with NAFLD/NASH in daily clinical practice.展开更多
Gastric cancer is one of the most frequent and lethal malignancies worldwide because of high frequency of metastasis. Tumor cell motility and invasion play fundamental roles in cancer metastasis. Recent studies have r...Gastric cancer is one of the most frequent and lethal malignancies worldwide because of high frequency of metastasis. Tumor cell motility and invasion play fundamental roles in cancer metastasis. Recent studies have revealed that the Rho/Rho-associated protein kinases(ROCK) pathway plays a critical role in the regulation of cancer cell motility and invasion. In addition,the Rho/ROCK pathway plays important roles in invasion and metastasis on the basis of its predominant function of cell cytoskeletal regulation in gastric cancer. According to the current understanding of tumor motility,there are two modes of tumor cell movement:mesenchymal and amoeboid. In addition,cancer cell movement can be interchangeable between the mesenchymal and amoeboid movements under certain conditions. Control of cell motility through the actin cytoskeleton creates the potential for regulating tumor cell metastasis. In this review we discuss Rho GTPases and ROCK signaling and describe the mechanisms of Rho/ROCK activity with regard to motility and metastasis in gastric cancer.In addition,we provide an insight of the therapeutic potential of targeting the Rho/ROCK pathway.展开更多
Although auxin and brassinosteroid （BR） synergistically control various plant responses, the molecular mechanism underlying the auxin-BR crosstalk is not wen understood. We previously identified SMOS1, an auxin-regu...Although auxin and brassinosteroid （BR） synergistically control various plant responses, the molecular mechanism underlying the auxin-BR crosstalk is not wen understood. We previously identified SMOS1, an auxin-regulated APETALA2-type transcription factor, as the causal gene of the small organ size 1 （smosl） mutant that is characterized by a decreased final size of various organs in rice. In this study, we identified another smos mutant, smos2, which shows the phenotype indistinguishable from smosl. SMOS2 was identical to the previously reported DWARF AND LOWoTILLERING （DLT）, which encodes a GRAS protein involved in BR signaling. SMOS1 and SMOS2/DLT physically interact to cooperatively enhance transcriptional transactivation activity in yeast and in rice nuclei. Consistently, the expression of OsPHI-1, a direct target of SMOS1, is upregulated only when SMOS1 and SMOS2/DLT proteins are both present in rice ceils. Taken together, our results suggest that SMOS1 and SMOS2/DLT form a keystone complex on auxin-BR signaling crosstalk in rice.展开更多
A 58-year-old man presented with the chief complaint of abdominal bloating and was incidentally found to have a liver tumor.As diagnostic imaging studies could not rule out malignancy,the patient underwent partial res...A 58-year-old man presented with the chief complaint of abdominal bloating and was incidentally found to have a liver tumor.As diagnostic imaging studies could not rule out malignancy,the patient underwent partial resection of segment 3 of the liver.The lesion pathologically showed eosinophilic proliferation,in addition to immunohistochemical positivity for human melanoma black 45 and Melan-A,thereby leading to the diagnosis of a hepatic perivascular epithelioid cell tumor(PEComa).A PEComa arising from the liver is relatively rare.Moreover,the name ‘PEComa' has not yet been widely recognized,and the same disease entity has been called epithelioid angiomyolipoma(EAML),further diminishing the recognition of PEComa.In addition,PEComa imaging findings mimic those of malignant liver tumors,and clinically,this tumor tends to enlarge.Therefore,a PEComa is difficult to diagnose.We conducted a systematic review of PEComa and EAML cases and discuss the results,including findings useful for differentiating perivascular epithelioid cell tumors from malignant liver tumors.展开更多
Lodging has been a major roadblock to attaining increased crop productivity. In an attempt to understand the mechanism for culm strength in rice, we isolated an effective quantitative trait locus （QTL）, STRONG CULM3...Lodging has been a major roadblock to attaining increased crop productivity. In an attempt to understand the mechanism for culm strength in rice, we isolated an effective quantitative trait locus （QTL）, STRONG CULM3 （SCM3）, the causal gene of which is identical to rice TEOSINTE BRANCHED1 （OsTB1）, a gene previously reported to positively control strigolactone （SL） signaling. A near-isogenic line （NIL） carrying SCM3 showed enhanced culm strength and increased spikelet number despite the expected decrease in tiller number, indicating that SL also has a positive role in enhancing culm strength and spikelet number. We produced a pyramiding line carrying SCM3 and SCM2, another QTL encoding AP01 involved in panicle development. The NIL-SCM2＋SCM3 showed a much stronger culm than NIL-SCM2 and NIL-SCM3 and an increased spikelet number caused by the additive effect of these QTLs. We discuss the importance of utilizing suitable alleles of these STRONG CULM QTLs without inducing detrimental traits for breeding.展开更多
AIM： To evaluate long-term follow-up of minimum-sized hepatocellular carcinoma （HCC） treated with percutaneous ethanol injection （PEI）. METHODS： PEI was applied to 42 lesions in 31 patients （23 male and eight f...AIM： To evaluate long-term follow-up of minimum-sized hepatocellular carcinoma （HCC） treated with percutaneous ethanol injection （PEI）. METHODS： PEI was applied to 42 lesions in 31 patients （23 male and eight female） with HCC 〈 15 mm in diameter, over the past 15 years. RESULTS： Overall survival rate was 74.1% at 3 years, 49.9% at 5 years, 27.2% at 7 years and 14.5% at 10 years. These results are superior to, or at least the same as those for hepatic resection and radiofrequency ablation. Survival was affected only by liver function, but not by sex, age, etiology of Hepatitis B virus or Hepatitis C virus, α-fetoprotein levels, arterial and portal blood flow, histological characteristics, and tumor multiplicity or size. Patients in Chiid-Pugh class A and B had 5-, 7- and 10-years survival rates of 76.0%, 42.2% and 15.8%, and 17.1%, 8.6% and 0%, respectively （P = 0.025）. CONCLUSION： Treatment with PEI is best indicated for patients with HCC 〈 15 mm in Child-Pugh class A.展开更多
The sentinel node(SN) technique has been established for the treatment of some types of solid cancers to avoid unnecessary lymphadenectomy. If node disease were diagnosed before surgery, minimal surgery with omission ...The sentinel node(SN) technique has been established for the treatment of some types of solid cancers to avoid unnecessary lymphadenectomy. If node disease were diagnosed before surgery, minimal surgery with omission of lymph node dissection would be an option for patients with early gastric cancer. Although SN biopsy has been well ascertained in the treatment of breast cancer and melanoma, SN navigation surgery(SNNS) in gastric cancer has not been yet universal due to the complicated lymphatic flow from the stomach. Satisfactory establishment of SNNS will result in the possible indication of minimally invasive surgery of gastric cancer. However, the results reported in the literature on SN biopsy in gastric cancer are widely divergent and many issues are still to be resolved, such as the collection method of SN, detection of micrometastasis in SN, and clinical benefit. The difference in the procedural technique and learning phase of surgeons is also varied the accuracy of SN mapping. In this review, we outline the current status of application for SNNS in gastric cancer.展开更多
Recent advances in molecular targeted therapies, including targeting human epidermal growth factor receptor 2(HER2), had a major forward step in the therapy for gastric cancer patients. Application of HER2-targeted th...Recent advances in molecular targeted therapies, including targeting human epidermal growth factor receptor 2(HER2), had a major forward step in the therapy for gastric cancer patients. Application of HER2-targeted therapies, in particular trastuzumab in combination with chemotherapy in metastatic HER2-positive gastric cancers, resulted in improvements in response rates, time to progression and overall survival. Nevertheless, as with breast cancer, many patients with gastric cancer develop resistance to trastuzumab. Several promising therapies are currently being developed in combination with chemotherapy to increase the efficacy and overcome the cancerresistance. Here we review the current overview of clinical application of agents targeting HER2 in gastric cancer. We also discuss the ongoing trials supporting the use of HER2-targeted agents combined with cytotoxic agents or other monoclonal antibodies.展开更多
Gastric cancer(GC)remains a leading cause of cancer-related death worldwide.Less than half of GC cases are diagnosed at an advanced stage due to its lack of early symptoms.GC is a heterogeneous disease associated with...Gastric cancer(GC)remains a leading cause of cancer-related death worldwide.Less than half of GC cases are diagnosed at an advanced stage due to its lack of early symptoms.GC is a heterogeneous disease associated with a number of genetic and somatic mutations.Early detection and effective monitoring of tumor progression are essential for reducing GC disease burden and mortality.The current widespread use of semi-invasive endoscopic methods and radiologic approaches has increased the number of treatable cancers:However,these approaches are invasive,costly,and time-consuming.Thus,novel molecular noninvasive tests that detect GC alterations seem to be more sensitive and specific compared to the current methods.Recent technological advances have enabled the detection of blood-based biomarkers that could be used as diagnostic indicators and for monitoring postsurgical minimal residual disease.These biomarkers include circulating DNA,RNA,extracellular vesicles,and proteins,and their clinical applications are currently being investigated.The identification of ideal diagnostic markers for GC that have high sensitivity and specificity would improve survival rates and contribute to the advancement of precision medicine.This review provides an overview of current topics regarding the novel,recently developed diagnostic markers for GC.展开更多
Type 2 diabetes is one of the most prevalent and serious metabolic diseases.Under diabetic conditions,chronic hyperglycemia and subsequent induction of oxidative stress deteriorate pancreaticβ-cell function,which lea...Type 2 diabetes is one of the most prevalent and serious metabolic diseases.Under diabetic conditions,chronic hyperglycemia and subsequent induction of oxidative stress deteriorate pancreaticβ-cell function,which leads to the aggravation of type 2 diabetes.Although such phenomena are well known as glucose toxicity,its molecular mechanism remains unclear.In this review article,we describe the possible molecular mechanism forβ-cell dysfunction found in type 2 diabetes,focusing on(1)oxidative stress,(2)pancreatic transcription factors(PDX-1 and MafA)and(3)incretin receptors(GLP-1 and GIP receptors).Under such conditions,nuclear expression levels of PDX-1 and MafA are decreased,which leads to suppression of insulin biosynthesis and secretion.In addition,expression levels of GLP-1 and GIP receptors are decreased,which likely contributes to the impaired incretin effects found in diabetes.Taken together,it is likely that downregulation of pancreatic transcription factors(PDX-1and MafA)and down-regulation of incretin receptors(GLP-1 and GIP receptors)explain,at least in part,the molecular mechanism forβ-cell dysfunction found in type 2 diabetes.展开更多
Fibroblast growth factor receptors(FGFRs) regulate a variety of cellular functions, from embryogenesis to adult tissue homeostasis. FGFR signaling also plays significant roles in the proliferation, invasion, and survi...Fibroblast growth factor receptors(FGFRs) regulate a variety of cellular functions, from embryogenesis to adult tissue homeostasis. FGFR signaling also plays significant roles in the proliferation, invasion, and survival of several types of tumor cells. FGFR-induced alterations, including gene amplification, chromosomal translocation, and mutations, have been shown to be associated with the tumor initiation and progression of gastric cancer, especially in diffuse-type cancers. Therefore, the FGFR signaling pathway might be one of the therapeutic targets in gastric cancer. This review aims to provide an overview of the role of FGFR signaling in tumorigenesis, tumor progression, proliferation, and chemoresistance. We also discuss the accumulating evidence that demonstrates the effectiveness of using clinical therapeutic agents to inhibit FGFR signaling for the treatment of gastric cancer.展开更多
Focal adhesion kinase(FAK)is a 125-kDa non-receptor protein tyrosine.Growth factors or the clustering of integrins facilitate the rapid phosphorylation of FAK at Tyr-397 and this in turn recruits Src-family protein ty...Focal adhesion kinase(FAK)is a 125-kDa non-receptor protein tyrosine.Growth factors or the clustering of integrins facilitate the rapid phosphorylation of FAK at Tyr-397 and this in turn recruits Src-family protein tyrosine kinases,resulting in the phosphorylation of Tyr-576 and Tyr-577 in the FAK activation loop and full catalytic FAK activation.FAK plays a critical role in the biological processes of normal and cancer cells including the gastrointestinal tract.FAK also plays an important role in the restitution,cell survival and apoptosis and carcinogenesis of the gastrointestinal tract.FAK is over-expressed in cancer cells and its over-expression and elevated activities are associated with motility and invasion of cancer cells.FAK has been proposed as a potential target in cancer therapy.Small molecule inhibitors effectively inhibit the kinase activity of FAK and show a potent inhibitory effect for the proliferation and migration of tumor cells,indicating a high potential for application in cancer therapy.展开更多
Gastrointestinal(GI)cancer has a high tumor incidence and mortality rate worldwide.Despite significant improvements in radiotherapy,chemotherapy,and targeted therapy for GI cancer over the last decade,GI cancer is cha...Gastrointestinal(GI)cancer has a high tumor incidence and mortality rate worldwide.Despite significant improvements in radiotherapy,chemotherapy,and targeted therapy for GI cancer over the last decade,GI cancer is characterized by high recurrence rates and a dismal prognosis.There is an urgent need for new diagnostic and therapeutic approaches.Recent technological advances and the accumulation of clinical data are moving toward the use of precision medicine in GI cancer.Here we review the application and status of precision medicine in GI cancer.Analyses of liquid biopsy specimens provide comprehensive real-time data of the tumor-associated changes in an individual GI cancer patient with malignancy.With the introduction of gene panels including next-generation sequencing,it has become possible to identify a variety of mutations and genetic biomarkers in GI cancer.Although the genomic aberration of GI cancer is apparently less actionable compared to other solid tumors,novel informative analyses derived from comprehensive gene profiling may lead to the discovery of precise molecular targeted drugs.These progressions will make it feasible to incorporate clinical,genome-based,and phenotype-based diagnostic and therapeutic approaches and apply them to individual GI cancer patients for precision medicine.展开更多
BACKGROUND:Out-of-hospital cardiac arrest(OHCA) is a public health concern, and many studies have been conducted on return of spontaneous circulation(ROSC) and its prognostic factors.Rotational thromboelastometry(ROTE...BACKGROUND:Out-of-hospital cardiac arrest(OHCA) is a public health concern, and many studies have been conducted on return of spontaneous circulation(ROSC) and its prognostic factors.Rotational thromboelastometry(ROTEM?), a point-of-care testing(POCT) method, has been useful for predicting ROSC in patients with OHCA, but very few studies have focused on patients with non-shockable rhythm. We examined whether the parameters of POCT could predict ROSC in patients with OHCA and accompanying non-shockable rhythm.METHODS:This is a single-center, retrospective observational study. Complete blood count,blood gas, and ROTEM POCT measurements were used. This study included patients with nontraumatic OHCA aged 18 years or older who were transported to the emergency department and evaluated using POCT between January 2013 and December 2021. The patients were divided into the ROSC and non-ROSC groups. Prehospital information and POCT parameters were compared using receiver operating characteristic(ROC) curve analysis, and further logistic regression analysis was performed.RESULTS:Sixty-seven and 135 patients were in the ROSC and non-ROSC groups,respectively. The ROC curves showed a high area under the curve(AUC) for K^(+) of 0.77(95%confidence interval [CI]:0.71–0.83) and EXTEM amplitude 5 min after clotting time(A5) of 0.70(95%CI:0.62–0.77). The odds ratios for ROSC were as follows:female sex 3.67(95%CI:1.67–8.04);K^(+)0.64(95%CI:0.48–0.84);and EXTEM A5 1.03(95%CI:1.01–1.06).CONCLUSION:In OHCA patients with non-shockable rhythm, K^(+) level and the ROTEM parameter EXTEM A5 may be useful in predicting ROSC.展开更多
AIM:To compare the imaging results with histology and to evaluate the diagnostic sensitivity of imaging modalities for hepatocellular carcinoma(HCC)smaller than 2 cm.METHODS:Nodules smaller than 2 cm(n=34)revealed by ...AIM:To compare the imaging results with histology and to evaluate the diagnostic sensitivity of imaging modalities for hepatocellular carcinoma(HCC)smaller than 2 cm.METHODS:Nodules smaller than 2 cm(n=34)revealed by ultrasonography(US)in 29 patients with liver cirrhosis were analyzed.Histological diagnosis of HCC was performed by ultrasonographic guidance:moderately-differentiated HCC(n=24);well-differentiated HCC(n=10).The patterns disclosed by the four imaging modalities defined the conclusive diagnosis of HCC:(1)contrast-enhanced computed tomography(CECT),hypervascularity in the arterial phase and washout in the equilibrium phase;(2)Sonazoid contrast-enhanced US(CEUS),hypervascularity in the early vascular phase and defect in the Kupffer phase;(3)gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid(Gd-EOBDTPA)-enhanced magnetic resonance imaging(MRI),hypervascularity in the arterial phase and/or defect in the hepatobiliary phase;and(4)CT arterioportal angiography:hypervascularity by CT during arteriography and/ or perfusion defect by CT during arterial portography.RESULTS:Overall,the sensitivity of diagnosing HCC smaller than 2 cm was 52.9%(18/34)(95%CI:35.170.2)by CECT;67.6%(23/34)(95%CI:49.5-82.6)by Sonazoid CEUS;76.5%(26/34)(95%CI:58.8-89.3) by Gd-EOB-DTPA MRI;and 88.2%(30/34)(95%CI: 72.5-96.7)by CT arterioportal angiography.The diagnostic sensitivity of detecting moderately-differentiated HCC by CECT,Sonazoid CEUS,Gd-EOB-DTPA MRI and CT arterioportal angiography was 62.5%(15/24)(95%CI: 40.6-81.2),79.2%(19/24)(95%CI:57.8-92.9),75.0% (18/24)(95%CI:53.3-90.2)and 95.8%(23/24)(95% CI:78.9-99.9),respectively.A significant difference(P< 0.05)was observed between CECT and CT arterioportal angiography in all nodules.There was no difference between Sonazoid CEUS,Gd-EOB-DTPA MRI,and CT arterioportal angiography.The combined sensitivity of Sonazoid CEUS and Gd-EOB-DTPA MRI was 94.1%(32/34).CONCLUSION:Changing the main diagnostic modality for HCC smaller than 2 cm from CT arterioportal angiography to Sonazoid C展开更多
文摘The number of patients with nonalcoholic fatty liver diseases(NAFLD) including nonalcoholic steatohepatitis(NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma(HCC) and is one of the most serious health problems in the world. The mechanism through which NASH progresses is still largely unknown. Activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD/NASH. Apoptotic hepatocytes stimulate immune cells and hepatic stellate cells toward the progression of fibrosis in the liver through the production of inflammasomes and cytokines. Abnormalities in glucose and lipid metabolism as well as microbiota accelerate these processes. The production of reactive oxygen species, oxidative stress, and endoplasmic reticulum stress is also involved. Cell death, including apoptosis, seems very important in the progression of NAFLD and NASH. Recently, inhibitors of apoptosis have been developed as drugs for the treatment of NASH and may prevent cirrhosis and HCC. Increased hepatocyte apoptosis may distinguish NASH from NAFLD, and the improvement of apoptosis could play a role in controlling the development of NASH. In this review, the association between apoptosis and NAFLD/NASH are discussed. This review could provide their knowledge, which plays a role in seeing the patients with NAFLD/NASH in daily clinical practice.
基金Supported by KAKENHI Grant-in-Aid for Scientific Research,No.23390329the National Cancer Center Research and Development Fund,No.23-A-9
文摘Gastric cancer is one of the most frequent and lethal malignancies worldwide because of high frequency of metastasis. Tumor cell motility and invasion play fundamental roles in cancer metastasis. Recent studies have revealed that the Rho/Rho-associated protein kinases(ROCK) pathway plays a critical role in the regulation of cancer cell motility and invasion. In addition,the Rho/ROCK pathway plays important roles in invasion and metastasis on the basis of its predominant function of cell cytoskeletal regulation in gastric cancer. According to the current understanding of tumor motility,there are two modes of tumor cell movement:mesenchymal and amoeboid. In addition,cancer cell movement can be interchangeable between the mesenchymal and amoeboid movements under certain conditions. Control of cell motility through the actin cytoskeleton creates the potential for regulating tumor cell metastasis. In this review we discuss Rho GTPases and ROCK signaling and describe the mechanisms of Rho/ROCK activity with regard to motility and metastasis in gastric cancer.In addition,we provide an insight of the therapeutic potential of targeting the Rho/ROCK pathway.
文摘Although auxin and brassinosteroid （BR） synergistically control various plant responses, the molecular mechanism underlying the auxin-BR crosstalk is not wen understood. We previously identified SMOS1, an auxin-regulated APETALA2-type transcription factor, as the causal gene of the small organ size 1 （smosl） mutant that is characterized by a decreased final size of various organs in rice. In this study, we identified another smos mutant, smos2, which shows the phenotype indistinguishable from smosl. SMOS2 was identical to the previously reported DWARF AND LOWoTILLERING （DLT）, which encodes a GRAS protein involved in BR signaling. SMOS1 and SMOS2/DLT physically interact to cooperatively enhance transcriptional transactivation activity in yeast and in rice nuclei. Consistently, the expression of OsPHI-1, a direct target of SMOS1, is upregulated only when SMOS1 and SMOS2/DLT proteins are both present in rice ceils. Taken together, our results suggest that SMOS1 and SMOS2/DLT form a keystone complex on auxin-BR signaling crosstalk in rice.
文摘A 58-year-old man presented with the chief complaint of abdominal bloating and was incidentally found to have a liver tumor.As diagnostic imaging studies could not rule out malignancy,the patient underwent partial resection of segment 3 of the liver.The lesion pathologically showed eosinophilic proliferation,in addition to immunohistochemical positivity for human melanoma black 45 and Melan-A,thereby leading to the diagnosis of a hepatic perivascular epithelioid cell tumor(PEComa).A PEComa arising from the liver is relatively rare.Moreover,the name ‘PEComa' has not yet been widely recognized,and the same disease entity has been called epithelioid angiomyolipoma(EAML),further diminishing the recognition of PEComa.In addition,PEComa imaging findings mimic those of malignant liver tumors,and clinically,this tumor tends to enlarge.Therefore,a PEComa is difficult to diagnose.We conducted a systematic review of PEComa and EAML cases and discuss the results,including findings useful for differentiating perivascular epithelioid cell tumors from malignant liver tumors.
文摘Lodging has been a major roadblock to attaining increased crop productivity. In an attempt to understand the mechanism for culm strength in rice, we isolated an effective quantitative trait locus （QTL）, STRONG CULM3 （SCM3）, the causal gene of which is identical to rice TEOSINTE BRANCHED1 （OsTB1）, a gene previously reported to positively control strigolactone （SL） signaling. A near-isogenic line （NIL） carrying SCM3 showed enhanced culm strength and increased spikelet number despite the expected decrease in tiller number, indicating that SL also has a positive role in enhancing culm strength and spikelet number. We produced a pyramiding line carrying SCM3 and SCM2, another QTL encoding AP01 involved in panicle development. The NIL-SCM2＋SCM3 showed a much stronger culm than NIL-SCM2 and NIL-SCM3 and an increased spikelet number caused by the additive effect of these QTLs. We discuss the importance of utilizing suitable alleles of these STRONG CULM QTLs without inducing detrimental traits for breeding.
文摘AIM： To evaluate long-term follow-up of minimum-sized hepatocellular carcinoma （HCC） treated with percutaneous ethanol injection （PEI）. METHODS： PEI was applied to 42 lesions in 31 patients （23 male and eight female） with HCC 〈 15 mm in diameter, over the past 15 years. RESULTS： Overall survival rate was 74.1% at 3 years, 49.9% at 5 years, 27.2% at 7 years and 14.5% at 10 years. These results are superior to, or at least the same as those for hepatic resection and radiofrequency ablation. Survival was affected only by liver function, but not by sex, age, etiology of Hepatitis B virus or Hepatitis C virus, α-fetoprotein levels, arterial and portal blood flow, histological characteristics, and tumor multiplicity or size. Patients in Chiid-Pugh class A and B had 5-, 7- and 10-years survival rates of 76.0%, 42.2% and 15.8%, and 17.1%, 8.6% and 0%, respectively （P = 0.025）. CONCLUSION： Treatment with PEI is best indicated for patients with HCC 〈 15 mm in Child-Pugh class A.
基金Partially funded by KAKENHI(Grant-in-Aid forScientific Research),No.23390329by the National Cancer Center Research and Development Fund(23-A-9)by PriorityResearch Fund of Osaka City University
文摘The sentinel node(SN) technique has been established for the treatment of some types of solid cancers to avoid unnecessary lymphadenectomy. If node disease were diagnosed before surgery, minimal surgery with omission of lymph node dissection would be an option for patients with early gastric cancer. Although SN biopsy has been well ascertained in the treatment of breast cancer and melanoma, SN navigation surgery(SNNS) in gastric cancer has not been yet universal due to the complicated lymphatic flow from the stomach. Satisfactory establishment of SNNS will result in the possible indication of minimally invasive surgery of gastric cancer. However, the results reported in the literature on SN biopsy in gastric cancer are widely divergent and many issues are still to be resolved, such as the collection method of SN, detection of micrometastasis in SN, and clinical benefit. The difference in the procedural technique and learning phase of surgeons is also varied the accuracy of SN mapping. In this review, we outline the current status of application for SNNS in gastric cancer.
基金KAKENHI(Grant-in-Aid for Scientific Research),No.23390329the National Cancer Center Research and Development Fund(23-A-9)
文摘Recent advances in molecular targeted therapies, including targeting human epidermal growth factor receptor 2(HER2), had a major forward step in the therapy for gastric cancer patients. Application of HER2-targeted therapies, in particular trastuzumab in combination with chemotherapy in metastatic HER2-positive gastric cancers, resulted in improvements in response rates, time to progression and overall survival. Nevertheless, as with breast cancer, many patients with gastric cancer develop resistance to trastuzumab. Several promising therapies are currently being developed in combination with chemotherapy to increase the efficacy and overcome the cancerresistance. Here we review the current overview of clinical application of agents targeting HER2 in gastric cancer. We also discuss the ongoing trials supporting the use of HER2-targeted agents combined with cytotoxic agents or other monoclonal antibodies.
基金the National Cancer Center Research and Development Fund,No.23-A-9.
文摘Gastric cancer(GC)remains a leading cause of cancer-related death worldwide.Less than half of GC cases are diagnosed at an advanced stage due to its lack of early symptoms.GC is a heterogeneous disease associated with a number of genetic and somatic mutations.Early detection and effective monitoring of tumor progression are essential for reducing GC disease burden and mortality.The current widespread use of semi-invasive endoscopic methods and radiologic approaches has increased the number of treatable cancers:However,these approaches are invasive,costly,and time-consuming.Thus,novel molecular noninvasive tests that detect GC alterations seem to be more sensitive and specific compared to the current methods.Recent technological advances have enabled the detection of blood-based biomarkers that could be used as diagnostic indicators and for monitoring postsurgical minimal residual disease.These biomarkers include circulating DNA,RNA,extracellular vesicles,and proteins,and their clinical applications are currently being investigated.The identification of ideal diagnostic markers for GC that have high sensitivity and specificity would improve survival rates and contribute to the advancement of precision medicine.This review provides an overview of current topics regarding the novel,recently developed diagnostic markers for GC.
文摘Type 2 diabetes is one of the most prevalent and serious metabolic diseases.Under diabetic conditions,chronic hyperglycemia and subsequent induction of oxidative stress deteriorate pancreaticβ-cell function,which leads to the aggravation of type 2 diabetes.Although such phenomena are well known as glucose toxicity,its molecular mechanism remains unclear.In this review article,we describe the possible molecular mechanism forβ-cell dysfunction found in type 2 diabetes,focusing on(1)oxidative stress,(2)pancreatic transcription factors(PDX-1 and MafA)and(3)incretin receptors(GLP-1 and GIP receptors).Under such conditions,nuclear expression levels of PDX-1 and MafA are decreased,which leads to suppression of insulin biosynthesis and secretion.In addition,expression levels of GLP-1 and GIP receptors are decreased,which likely contributes to the impaired incretin effects found in diabetes.Taken together,it is likely that downregulation of pancreatic transcription factors(PDX-1and MafA)and down-regulation of incretin receptors(GLP-1 and GIP receptors)explain,at least in part,the molecular mechanism forβ-cell dysfunction found in type 2 diabetes.
基金Supported by KAKENHI(partiallyGrant-in-Aid for Scientific ResearchNo.23390329)
文摘Fibroblast growth factor receptors(FGFRs) regulate a variety of cellular functions, from embryogenesis to adult tissue homeostasis. FGFR signaling also plays significant roles in the proliferation, invasion, and survival of several types of tumor cells. FGFR-induced alterations, including gene amplification, chromosomal translocation, and mutations, have been shown to be associated with the tumor initiation and progression of gastric cancer, especially in diffuse-type cancers. Therefore, the FGFR signaling pathway might be one of the therapeutic targets in gastric cancer. This review aims to provide an overview of the role of FGFR signaling in tumorigenesis, tumor progression, proliferation, and chemoresistance. We also discuss the accumulating evidence that demonstrates the effectiveness of using clinical therapeutic agents to inhibit FGFR signaling for the treatment of gastric cancer.
文摘Focal adhesion kinase(FAK)is a 125-kDa non-receptor protein tyrosine.Growth factors or the clustering of integrins facilitate the rapid phosphorylation of FAK at Tyr-397 and this in turn recruits Src-family protein tyrosine kinases,resulting in the phosphorylation of Tyr-576 and Tyr-577 in the FAK activation loop and full catalytic FAK activation.FAK plays a critical role in the biological processes of normal and cancer cells including the gastrointestinal tract.FAK also plays an important role in the restitution,cell survival and apoptosis and carcinogenesis of the gastrointestinal tract.FAK is over-expressed in cancer cells and its over-expression and elevated activities are associated with motility and invasion of cancer cells.FAK has been proposed as a potential target in cancer therapy.Small molecule inhibitors effectively inhibit the kinase activity of FAK and show a potent inhibitory effect for the proliferation and migration of tumor cells,indicating a high potential for application in cancer therapy.
基金Supported by KAKENHI(Grant-in-Aid for Scientific Research),No.18H02883
文摘Gastrointestinal(GI)cancer has a high tumor incidence and mortality rate worldwide.Despite significant improvements in radiotherapy,chemotherapy,and targeted therapy for GI cancer over the last decade,GI cancer is characterized by high recurrence rates and a dismal prognosis.There is an urgent need for new diagnostic and therapeutic approaches.Recent technological advances and the accumulation of clinical data are moving toward the use of precision medicine in GI cancer.Here we review the application and status of precision medicine in GI cancer.Analyses of liquid biopsy specimens provide comprehensive real-time data of the tumor-associated changes in an individual GI cancer patient with malignancy.With the introduction of gene panels including next-generation sequencing,it has become possible to identify a variety of mutations and genetic biomarkers in GI cancer.Although the genomic aberration of GI cancer is apparently less actionable compared to other solid tumors,novel informative analyses derived from comprehensive gene profiling may lead to the discovery of precise molecular targeted drugs.These progressions will make it feasible to incorporate clinical,genome-based,and phenotype-based diagnostic and therapeutic approaches and apply them to individual GI cancer patients for precision medicine.
文摘BACKGROUND:Out-of-hospital cardiac arrest(OHCA) is a public health concern, and many studies have been conducted on return of spontaneous circulation(ROSC) and its prognostic factors.Rotational thromboelastometry(ROTEM?), a point-of-care testing(POCT) method, has been useful for predicting ROSC in patients with OHCA, but very few studies have focused on patients with non-shockable rhythm. We examined whether the parameters of POCT could predict ROSC in patients with OHCA and accompanying non-shockable rhythm.METHODS:This is a single-center, retrospective observational study. Complete blood count,blood gas, and ROTEM POCT measurements were used. This study included patients with nontraumatic OHCA aged 18 years or older who were transported to the emergency department and evaluated using POCT between January 2013 and December 2021. The patients were divided into the ROSC and non-ROSC groups. Prehospital information and POCT parameters were compared using receiver operating characteristic(ROC) curve analysis, and further logistic regression analysis was performed.RESULTS:Sixty-seven and 135 patients were in the ROSC and non-ROSC groups,respectively. The ROC curves showed a high area under the curve(AUC) for K^(+) of 0.77(95%confidence interval [CI]:0.71–0.83) and EXTEM amplitude 5 min after clotting time(A5) of 0.70(95%CI:0.62–0.77). The odds ratios for ROSC were as follows:female sex 3.67(95%CI:1.67–8.04);K^(+)0.64(95%CI:0.48–0.84);and EXTEM A5 1.03(95%CI:1.01–1.06).CONCLUSION:In OHCA patients with non-shockable rhythm, K^(+) level and the ROTEM parameter EXTEM A5 may be useful in predicting ROSC.
文摘AIM:To compare the imaging results with histology and to evaluate the diagnostic sensitivity of imaging modalities for hepatocellular carcinoma(HCC)smaller than 2 cm.METHODS:Nodules smaller than 2 cm(n=34)revealed by ultrasonography(US)in 29 patients with liver cirrhosis were analyzed.Histological diagnosis of HCC was performed by ultrasonographic guidance:moderately-differentiated HCC(n=24);well-differentiated HCC(n=10).The patterns disclosed by the four imaging modalities defined the conclusive diagnosis of HCC:(1)contrast-enhanced computed tomography(CECT),hypervascularity in the arterial phase and washout in the equilibrium phase;(2)Sonazoid contrast-enhanced US(CEUS),hypervascularity in the early vascular phase and defect in the Kupffer phase;(3)gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid(Gd-EOBDTPA)-enhanced magnetic resonance imaging(MRI),hypervascularity in the arterial phase and/or defect in the hepatobiliary phase;and(4)CT arterioportal angiography:hypervascularity by CT during arteriography and/ or perfusion defect by CT during arterial portography.RESULTS:Overall,the sensitivity of diagnosing HCC smaller than 2 cm was 52.9%(18/34)(95%CI:35.170.2)by CECT;67.6%(23/34)(95%CI:49.5-82.6)by Sonazoid CEUS;76.5%(26/34)(95%CI:58.8-89.3) by Gd-EOB-DTPA MRI;and 88.2%(30/34)(95%CI: 72.5-96.7)by CT arterioportal angiography.The diagnostic sensitivity of detecting moderately-differentiated HCC by CECT,Sonazoid CEUS,Gd-EOB-DTPA MRI and CT arterioportal angiography was 62.5%(15/24)(95%CI: 40.6-81.2),79.2%(19/24)(95%CI:57.8-92.9),75.0% (18/24)(95%CI:53.3-90.2)and 95.8%(23/24)(95% CI:78.9-99.9),respectively.A significant difference(P< 0.05)was observed between CECT and CT arterioportal angiography in all nodules.There was no difference between Sonazoid CEUS,Gd-EOB-DTPA MRI,and CT arterioportal angiography.The combined sensitivity of Sonazoid CEUS and Gd-EOB-DTPA MRI was 94.1%(32/34).CONCLUSION:Changing the main diagnostic modality for HCC smaller than 2 cm from CT arterioportal angiography to Sonazoid C
