A primary benign schwannoma of the liver is extremely rare and is difficult to preoperatively discriminate from a malignant tumor.We compared the imaging and pathological findings,and examined the possibility of preop...A primary benign schwannoma of the liver is extremely rare and is difficult to preoperatively discriminate from a malignant tumor.We compared the imaging and pathological findings,and examined the possibility of preoperatively diagnosing a benign liver schwannoma.A 72-year-old woman was admitted to our hospital because of a 4.6-cm mass in the liver.A malignant tumor was suspected,and a right hepatectomy was performed.After this,the diagnosis of a primary benign schwannoma of the liver was made through pathological examination.Contrast-enhanced ultrasonography(CEUS) with Sonazoid showed minute blood flows into the septum and solid areas of the tumor in the vascular phase;most likely due to increased arterial flow associated with infiltration of chronic inflammatory cells.In the postvascular phase,CEUS showed contrast defect of cystic areas and delayed enhancement of solid areas;most likely due to aggregation of siderophores.Because discriminating between a benign and malignant schwannoma of the liver is difficult,surgery is generally recommended.However,the two key findings from CEUS may be useful in discriminating ancient schwannoma by recognizing the hemorrhage involved in the secondary degeneration and aggregation of siderophores.展开更多
Gastric cancer represents a serious health problem on a global scale. It is the second leading cause of cancer-related death worldwide. Novel therapeutic targets are desperately needed because the meager improvement i...Gastric cancer represents a serious health problem on a global scale. It is the second leading cause of cancer-related death worldwide. Novel therapeutic targets are desperately needed because the meager improvement in the cure rate of about 10% realized by adjunctive treatments to surgery is unacceptable as > 50% patients with localized gastric cancer succumb to their disease. Either postoperative chemoradiotherapy (United States), pre-and post-operative chemotherapy (Europe), and adjuvant chemotherapy after a D2 resection (Asia) can all be regarded as standards of care in the localized gastric cancer management. In metastatic disease the addition of trastuzumab to chemotherapy is standard of care in Her2 positive disease. In the HER2 negative population, the treatments remain limited. In the first line setting, the standard of care is a combination of fluoropyrimidine and platinum containing chemotherapy, with or without epirubicin or docetaxel. The results of targeted therapy trials have by and large been disappointing, but none of these trials looked at an appropriately enriched population. Finally there is a meager overall survival benefit in treating patients with metastatic disease in the second line setting, with either irinotecan, docetaxel or ramucirumab however none of these drugs have been compared head to head in a well-powered randomized controlled trial.展开更多
S-1 is an oral 5-fluorouracil(5-FU) prodrug,which is designed to improve the antitumor activity of 5-FU by inhibiting dihydropyrimidine dehydrogenase,the key enzyme of 5-FU catabolism.Recently,two important studies on...S-1 is an oral 5-fluorouracil(5-FU) prodrug,which is designed to improve the antitumor activity of 5-FU by inhibiting dihydropyrimidine dehydrogenase,the key enzyme of 5-FU catabolism.Recently,two important studies on the clinical use of S-1 for pancreatic cancer have been reported from Japan.In the first study(GEST study),S-1 demonstrated non-inferiority to gemcitabine(GEM) in overall survival(OS) for metastatic or locally advanced pancreatic cancer,but combination chemotherapy with GEM and S-1 did not show superiority to GEM in OS.In the second study(JASPAC-01 study),S-1 showed superiority to adjuvant chemotherapy with GEM in OS in patients with resected pancreatic cancer.In addition to GEM,S-1 is now regarded as the key drug in the management of pancreatic cancer in Japan.To date,many studies have investigated the effectiveness of S-1 in various settings,such as first-line chemotherapy for metastatic or locally advanced pancreatic cancer,second-line chemotherapy after GEM failure,and chemoradiotherapy for locally advanced disease.In this review,we focus on recent clinical trials of S-1-based chemotherapy for advanced pancreatic cancer.展开更多
Surgical management of gastric cancer improves survival.However,for some time,surgeons have had diverse opinions about the extent of gastrectomy.Researchers have conducted many clinical studies,making slow but steady ...Surgical management of gastric cancer improves survival.However,for some time,surgeons have had diverse opinions about the extent of gastrectomy.Researchers have conducted many clinical studies,making slow but steady progress in determining the optimal surgical approach.The extent of lymph node dissection has been one of the major issues in surgery for gastric cancer.Many trials demonstrated that D2 dissection resulted in greater morbidity and mortality than D1 dissection.However,long-term outcomes demonstrated that D2 dissection resulted in longer survival than D1 dissection.In 2004,the Japan Clinical Oncology Group reported a pivotal trial which was performed to determine whether para-aortic lymph node dissection combined with D2 dissection was superior to D2 dissection alone and found no benefit of the additional surgery.Gastrectomy with pancreatectomy,splenectomy,and bursectomy was initially recommended as part of the D2 dissection.Now,pancreas-preserving total gastrectomy with D2 dissection is standard,and ongoing trials are addressing the role of splenectomy.Furthermore,the feasibility and safety of laparoscopic gastrectomy are well established.Survival and quality of life are increasingly recognized as the most important endpoints.In this review,we present perspectives on surgical techniques and important trials of these techniques in gastric cancer patients.展开更多
BACKGROUND High-grade pancreatic intraepithelial neoplasia(PanIN)exhibits no mass and is not detected by any examination modalities.However,it can be diagnosed by pancreatic juice cytology from indirect findings.Most ...BACKGROUND High-grade pancreatic intraepithelial neoplasia(PanIN)exhibits no mass and is not detected by any examination modalities.However,it can be diagnosed by pancreatic juice cytology from indirect findings.Most previous cases were diagnosed based on findings of a focal stricture of the main pancreatic duct(MPD)and caudal MPD dilatation and subsequent pancreatic juice cytology using endoscopic retrograde cholangiopancreatography(ERCP).We experienced a case of high-grade PanIN with an unclear MPD over a 20-mm range,but without caudal MPD dilatation on magnetic resonance cholangiopancreatography(MRCP).CASE SUMMARY A 60-year-old female patient underwent computed tomography for a follow-up of uterine cancer post-excision,which revealed pancreatic cysts.MRCP revealed an unclear MPD of the pancreatic body at a 20-mm length without caudal MPD dilatation.Thus,course observation was performed.After 24 mo,MRCP revealed an increased caudal MPD caliber and a larger pancreatic cyst.We performed ERCP and detected atypical cells suspected of adenocarcinoma by serial pancreatic juice aspiration cytology examination.We performed a distal pancreatectomy and obtained a histopathological diagnosis of high-grade PanIN.Pancreatic parenchyma invasion was not observed,and curative resection was achieved.CONCLUSION High-grade Pan-IN may cause MPD narrowing in a long range without caudal MPD dilatation.展开更多
AIM To investigate the clinical utility of alpha-fetoprotein(AFP)-producing gastric cancer(AFPGC)-specific microRNA(mi RNA)for monitoring and prognostic prediction of patients.METHODS We performed a comprehensive miRN...AIM To investigate the clinical utility of alpha-fetoprotein(AFP)-producing gastric cancer(AFPGC)-specific microRNA(mi RNA)for monitoring and prognostic prediction of patients.METHODS We performed a comprehensive miRNA array-based approach to compare miRNA expression levels between AFP-positive and AFP-negative cells in three patients with primary AFPGC.We next examined the expression levels of the selected miRNAs in five AFPGC and ten non-AFPGC tissue samples by quantitative reverse transcription-polymerase chain reaction to validate their utility.We also investigated the expression levels of the selected miRNA not only in tissue but also in plasma samples.Moreover,we investigated the relationship between plasma AFP levels and plasma selected miRNA expression levels,and also investigated the correlation of the selected miRNA expression levels and malignant potential.RESULTS Among the five miRNAs selected from the miRNA array results,the expression levels of miR-122-5p were significantly higher in the AFPGC patients than in the non-AFPGC patients(P<0.05).In tissue samples,mi R-122-5p expression level tended to be lower in the non-AFPGC tissue than the normal gastric mucosa.Conversely,in the AFPGC tissue,miR-122-5p expression level was significantly higher in the AFPGC tissue than both the normal gastric mucosa and the nonAFPGC tissue samples(P<0.05).Plasma mi R-122-5p expression levels were also significantly higher in the AFPGC patients than the health volunteers and the nonAFPGC patients(P<0.05)and were strongly correlated with plasma AFP levels(r=0.7975,P<0.0001).Moreover,the correlation of miR-122-5p expression in tissue samples with malignant potential was stronger than that of plasma AFP level in the AFPGC patients.In contrast,no correlation was found between mi R-122-5p expression levels and liver metastasis in the non-AFPGC patients.CONCLUSION miR-122-5p might be a useful biomarker for early detection and disease monitoring in AFPGC.展开更多
Although perifollicular repigmentation in the vitiligo lesions is owing to activation of follicular melanocyte stem cells and/or precursor cells followed by supplying matured melanocytes, the underlying mechanism of d...Although perifollicular repigmentation in the vitiligo lesions is owing to activation of follicular melanocyte stem cells and/or precursor cells followed by supplying matured melanocytes, the underlying mechanism of diffuse repigmentation on the whole vitiligo surface remains still unknown. In addition to the presence of remaining melanocytes, it is conceivable that dermal melanocyte precursor cells contribute to induce diffuse repigmentation after treatment. Therefore, we investigated here whether dermal and follicular melanocyte precursor cells were reduced or not in vitiligo lesions. We performed an immunostaining for Nestin and p75NGFR as dermal melanocyte precursor cells and MITF/Fzd4 as follicular melanocyte precursor cells and compared the positive cells number between lesions and non-lesions (n = 11). Although MITF<sup>+</sup>/Fzd4<sup>+</sup> cells in the hair follicle were significantly decreased in number in the lesions, Nestin<sup>+</sup> and p75NGFR<sup>+</sup> cells were not. This result indicates that dermal precursor cells could be retained in the vitiligo lesions but be disturbed to differentiate into matured melanocytes.展开更多
BACKGROUND Recent advancements in biliary tract cancer(BTC)treatment have expanded beyond surgery to include adjuvant therapy,yet the prognosis remains poor.Identifying prognostic biomarkers could enhance the assessme...BACKGROUND Recent advancements in biliary tract cancer(BTC)treatment have expanded beyond surgery to include adjuvant therapy,yet the prognosis remains poor.Identifying prognostic biomarkers could enhance the assessment of patients who have undergone radical resection for BTC.AIM To determine transmembrane serine protease 4(TMPRSS4)utility as a prognostic biomarker of radical resection for BTC.METHODS Medical records of patients who underwent radical resection for BTC,excluding intrahepatic cholangiocarcinoma,were retrospectively reviewed.The associations between TMPRSS4 expression and clinicopathological factors,overall survival,and recurrence-free survival were analyzed.RESULTS Among the 85 patients undergoing radical resection for BTC,46(54%)were TMPRSS4-positive.The TMPRSS4-positive group exhibited significantly higher preoperative carbohydrate antigen 19-9(CA19-9)values and greater lymphatic invasion than the TMPRSS4-negative group(P=0.019 and 0.039,respectively).Postoperative overall survival and recurrence-free survival were significantly worse in the TMPRSS4-positive group(median survival time:25.3 months vs not reached,P<0.001;median survival time:28.7 months vs not reached,P=0.043,respectively).Multivariate overall survival analysis indicated TMPRSS4 positivity,pT3/T4,and resection status R1 were independently associated with poor prognosis(P=0.032,0.035 and 0.030,respectively).TMPRSS4 positivity correlated with preoperative CA19-9 values≥37 U/mL and pathological tumor size≥30 mm(P=0.016 and 0.038,respectively).CONCLUSION TMPRSS4 is a potential prognostic biomarker of radical resection for BTC.展开更多
A long-pulse plasma discharge for more than 30 min. was achieved on the Large Helical Device （LHD）. A plasma of ne = 0.8 × 10^19 m^-3 and T10 = 2.0 keV was sustained with PICH = 0.52 MW, PECH = 0.1 MW and avera...A long-pulse plasma discharge for more than 30 min. was achieved on the Large Helical Device （LHD）. A plasma of ne = 0.8 × 10^19 m^-3 and T10 = 2.0 keV was sustained with PICH = 0.52 MW, PECH = 0.1 MW and averaged PNBI = 0.067 MW. Total injected heating energy was 1.3 G J, which was a quarter of the prepared RF heating energy. One of the keys to the success of the experiment was a dispersion of the local plasma heat load to divertors, accomplished by shifting the magnetic axis inward and outward.展开更多
A CO<sub>2</sub> capture system without supercritical CO<sub>2</sub> was optimized for mixtures of hydrophobic room temperature ionic liquids (RTILs) and propanol. We tested RTILs using bis(tri...A CO<sub>2</sub> capture system without supercritical CO<sub>2</sub> was optimized for mixtures of hydrophobic room temperature ionic liquids (RTILs) and propanol. We tested RTILs using bis(trifluoromethanesulfonyl)imide, TFSI-, anion and four quaternary ammonium cations, two quaternary phosphonium cations, and one imidazolium cation. The addition of 2-propanol into the RTILs clearly promoted the capture of normal CO<sub>2</sub>(nCO<sub>2</sub>) at ambient temperature and pressure. When combined with 2-propanol, the most efficient RTILs for nCO<sub>2</sub> capture were N-butyl-N,N,N-trimethylammonium TFSI-. This enhancement of nCO<sub>2</sub> capture was not observed in RTIL mixtures with 1-propanol or in propanol mixtures containing other phosphonium- and imidazolium-based RTILs. The torsion angle of TFSI-, which was calculated using density functional theory, is thought to be related to high nCO<sub>2</sub> capture efficiently.展开更多
Osteocytes are the most abundant cells in bone,which is a frequent site of breast cancer metastasis.Here,we focused on Wnt signaling and evaluated tumor-osteocyte interactions.In animal experiments,mammary tumor cells...Osteocytes are the most abundant cells in bone,which is a frequent site of breast cancer metastasis.Here,we focused on Wnt signaling and evaluated tumor-osteocyte interactions.In animal experiments,mammary tumor cells were inoculated into the mammary fat pad and tibia.The role of Lrp5-mediated Wnt signaling was examined by overexpressing and silencing Lrp5 in osteocytes and establishing a conditional knockout mouse model.The results revealed that administration of osteocytes or their conditioned medium(CM)inhibited tumor progression and osteolysis.Osteocytes overexpressing Lrp5 or β-catenin displayed strikingly elevated tumor-suppressive activity,accompanied by downregulation of tumor-promoting chemokines and upregulation of apoptosis-inducing and tumor-suppressing proteins such as p53.The antitumor effect was also observed with osteocyte-derived CM that was pretreated with a Wnt-activating compound.Notably,silencing Lrp5 in tumors inhibited tumor progression,while silencing Lrp5 in osteocytes in conditional knockout mice promoted tumor progression.Osteocytes exhibited elevated Lrp5 expression in response to tumor cells,implying that osteocytes protect bone through canonical Wnt signaling.Thus,our results suggest that the Lrp5/β-catenin axis activates tumor-promoting signaling in tumor cells but tumor-suppressive signaling in osteocytes.We envision that osteocytes with Wnt activation potentially offer a novel cell-based therapy for breast cancer and osteolytic bone metastasis.展开更多
A quantitative analysis method of CO_(2) laser treatments promotes laser treatment performance and rapid clinical application of novel treatment devices.The in silico clinical trial approach,which is based on computat...A quantitative analysis method of CO_(2) laser treatments promotes laser treatment performance and rapid clinical application of novel treatment devices.The in silico clinical trial approach,which is based on computational simulation of light-tissue interactions using the mathematical model,can provide quantitative data.Although several simulation methods of laser tissue vaporization with CO_(2) laser treatments have been proposed,validations of the CO_(2) laser wavelength have been insuffcient.In this study,we demonstrated a tissue vaporization simulation using a CO_(2) laser and performed the experimental validation using a hydrogel phantom with constant physical parameters to evaluate the simulation accuracy of the vaporization process.The laser tissue vaporization simulation consists of the calculation of light transport,photothermal conversion,thermal diffusion,and phase change in the tissue.The vaporization width,depth,and area with CO_(2) laser irradiation to a tissue model were simulated.The simulated results differed from the actual vaporization width and depth by approximately 20%and 30%,respectively,because of the solubilization of the hydrogel phantom.Alternatively,the simulation vaporization area for all light irradiation parameters,which is related to the vaporization amount,agreed well with the actual vaporization values.These results suggest that the computational simulation can be used to evaluate the amount of tissue vaporization in the safety and effectiveness analysis of CO_(2) laser treatments.展开更多
Mechanical loading to the bone is known to be beneficial for bone homeostasis and for suppressing tumor-induced osteolysis in the loaded bone.However,whether loading to a weight-bearing hind limb can inhibit distant t...Mechanical loading to the bone is known to be beneficial for bone homeostasis and for suppressing tumor-induced osteolysis in the loaded bone.However,whether loading to a weight-bearing hind limb can inhibit distant tumor growth in the brain is unknown.We examined the possibility of bone-to-brain mechanotransduction using a mouse model of a brain tumor by focusing on the response to Lrp5-mediated Wnt signaling and dopamine in tumor cells.The results revealed that loading the tibia with elevated levels of tyrosine hydroxylase,a rate-limiting enzyme in dopamine synthesis,markedly reduced the progression of the brain tumors.The simultaneous application of fluphenazine(FP),an antipsychotic dopamine modulator,enhanced tumor suppression.Dopamine and FP exerted antitumor effects through the dopamine receptors DRD1 and DRD2,respectively.Notably,dopamine downregulated Lrp5 via DRD1 in tumor cells.A cytokine array analysis revealed that the reduction in CCN4 was critical for loading-driven,dopamine-mediated tumor suppression.The silencing of Lrp5 reduced CCN4,and the administration of CCN4 elevated oncogenic genes such as MMP9,Runx2,and Snail.In summary,this study demonstrates that mechanical loading regulates dopaminergic signaling and remotely suppresses brain tumors by inhibiting the Lrp5-CCN4 axis via DRD1,indicating the possibility of developing an adjuvant bone-mediated loading therapy.展开更多
The impact of rotavirus (RV) vaccination in reducing severe rotavirus gastroenteritis (RVGE) in outpatient settings was prospectively surveyed in three pediatric clinics in Shibata City. In children younger than 3 yea...The impact of rotavirus (RV) vaccination in reducing severe rotavirus gastroenteritis (RVGE) in outpatient settings was prospectively surveyed in three pediatric clinics in Shibata City. In children younger than 3 years of age, the occurrence of severe RVGE among all acute gastroenteritis (AGE) was found to be significantly lower in three seasons after introduction of RV vaccines, compared to that in 2011, before introduction of RV vaccines. The incidence rates of severe RVGE among children younger than 3 years of age were found to be reduced by 71.2%, 47.7%, and 81.1% for 2012, 2013, and 2014, respectively, compared to that in 2011. These results suggest that the RV vaccination is effective for the prevention of severe RVGE in Japanese voluntary RV vaccination settings with estimated coverage rates of 32.5%, 40.5% and 47.1% for 2012, 2013 and 2014, respectively. It is expected that the reducing effect on severe RVGE would be persistently established by increasing the vaccine coverage rates.展开更多
文摘A primary benign schwannoma of the liver is extremely rare and is difficult to preoperatively discriminate from a malignant tumor.We compared the imaging and pathological findings,and examined the possibility of preoperatively diagnosing a benign liver schwannoma.A 72-year-old woman was admitted to our hospital because of a 4.6-cm mass in the liver.A malignant tumor was suspected,and a right hepatectomy was performed.After this,the diagnosis of a primary benign schwannoma of the liver was made through pathological examination.Contrast-enhanced ultrasonography(CEUS) with Sonazoid showed minute blood flows into the septum and solid areas of the tumor in the vascular phase;most likely due to increased arterial flow associated with infiltration of chronic inflammatory cells.In the postvascular phase,CEUS showed contrast defect of cystic areas and delayed enhancement of solid areas;most likely due to aggregation of siderophores.Because discriminating between a benign and malignant schwannoma of the liver is difficult,surgery is generally recommended.However,the two key findings from CEUS may be useful in discriminating ancient schwannoma by recognizing the hemorrhage involved in the secondary degeneration and aggregation of siderophores.
文摘Gastric cancer represents a serious health problem on a global scale. It is the second leading cause of cancer-related death worldwide. Novel therapeutic targets are desperately needed because the meager improvement in the cure rate of about 10% realized by adjunctive treatments to surgery is unacceptable as > 50% patients with localized gastric cancer succumb to their disease. Either postoperative chemoradiotherapy (United States), pre-and post-operative chemotherapy (Europe), and adjuvant chemotherapy after a D2 resection (Asia) can all be regarded as standards of care in the localized gastric cancer management. In metastatic disease the addition of trastuzumab to chemotherapy is standard of care in Her2 positive disease. In the HER2 negative population, the treatments remain limited. In the first line setting, the standard of care is a combination of fluoropyrimidine and platinum containing chemotherapy, with or without epirubicin or docetaxel. The results of targeted therapy trials have by and large been disappointing, but none of these trials looked at an appropriately enriched population. Finally there is a meager overall survival benefit in treating patients with metastatic disease in the second line setting, with either irinotecan, docetaxel or ramucirumab however none of these drugs have been compared head to head in a well-powered randomized controlled trial.
文摘S-1 is an oral 5-fluorouracil(5-FU) prodrug,which is designed to improve the antitumor activity of 5-FU by inhibiting dihydropyrimidine dehydrogenase,the key enzyme of 5-FU catabolism.Recently,two important studies on the clinical use of S-1 for pancreatic cancer have been reported from Japan.In the first study(GEST study),S-1 demonstrated non-inferiority to gemcitabine(GEM) in overall survival(OS) for metastatic or locally advanced pancreatic cancer,but combination chemotherapy with GEM and S-1 did not show superiority to GEM in OS.In the second study(JASPAC-01 study),S-1 showed superiority to adjuvant chemotherapy with GEM in OS in patients with resected pancreatic cancer.In addition to GEM,S-1 is now regarded as the key drug in the management of pancreatic cancer in Japan.To date,many studies have investigated the effectiveness of S-1 in various settings,such as first-line chemotherapy for metastatic or locally advanced pancreatic cancer,second-line chemotherapy after GEM failure,and chemoradiotherapy for locally advanced disease.In this review,we focus on recent clinical trials of S-1-based chemotherapy for advanced pancreatic cancer.
基金supported by multidisciplinary grants from The University of Texas MD Anderson Cancer Centersupported in part by the National Cancer Institute,National Institutes of Health(No.CAl 38671, CAl72741,and CAl50334 to JAA)the Biostatistics Resource Group(No. P30CA016672)
文摘Surgical management of gastric cancer improves survival.However,for some time,surgeons have had diverse opinions about the extent of gastrectomy.Researchers have conducted many clinical studies,making slow but steady progress in determining the optimal surgical approach.The extent of lymph node dissection has been one of the major issues in surgery for gastric cancer.Many trials demonstrated that D2 dissection resulted in greater morbidity and mortality than D1 dissection.However,long-term outcomes demonstrated that D2 dissection resulted in longer survival than D1 dissection.In 2004,the Japan Clinical Oncology Group reported a pivotal trial which was performed to determine whether para-aortic lymph node dissection combined with D2 dissection was superior to D2 dissection alone and found no benefit of the additional surgery.Gastrectomy with pancreatectomy,splenectomy,and bursectomy was initially recommended as part of the D2 dissection.Now,pancreas-preserving total gastrectomy with D2 dissection is standard,and ongoing trials are addressing the role of splenectomy.Furthermore,the feasibility and safety of laparoscopic gastrectomy are well established.Survival and quality of life are increasingly recognized as the most important endpoints.In this review,we present perspectives on surgical techniques and important trials of these techniques in gastric cancer patients.
文摘BACKGROUND High-grade pancreatic intraepithelial neoplasia(PanIN)exhibits no mass and is not detected by any examination modalities.However,it can be diagnosed by pancreatic juice cytology from indirect findings.Most previous cases were diagnosed based on findings of a focal stricture of the main pancreatic duct(MPD)and caudal MPD dilatation and subsequent pancreatic juice cytology using endoscopic retrograde cholangiopancreatography(ERCP).We experienced a case of high-grade PanIN with an unclear MPD over a 20-mm range,but without caudal MPD dilatation on magnetic resonance cholangiopancreatography(MRCP).CASE SUMMARY A 60-year-old female patient underwent computed tomography for a follow-up of uterine cancer post-excision,which revealed pancreatic cysts.MRCP revealed an unclear MPD of the pancreatic body at a 20-mm length without caudal MPD dilatation.Thus,course observation was performed.After 24 mo,MRCP revealed an increased caudal MPD caliber and a larger pancreatic cyst.We performed ERCP and detected atypical cells suspected of adenocarcinoma by serial pancreatic juice aspiration cytology examination.We performed a distal pancreatectomy and obtained a histopathological diagnosis of high-grade PanIN.Pancreatic parenchyma invasion was not observed,and curative resection was achieved.CONCLUSION High-grade Pan-IN may cause MPD narrowing in a long range without caudal MPD dilatation.
文摘AIM To investigate the clinical utility of alpha-fetoprotein(AFP)-producing gastric cancer(AFPGC)-specific microRNA(mi RNA)for monitoring and prognostic prediction of patients.METHODS We performed a comprehensive miRNA array-based approach to compare miRNA expression levels between AFP-positive and AFP-negative cells in three patients with primary AFPGC.We next examined the expression levels of the selected miRNAs in five AFPGC and ten non-AFPGC tissue samples by quantitative reverse transcription-polymerase chain reaction to validate their utility.We also investigated the expression levels of the selected miRNA not only in tissue but also in plasma samples.Moreover,we investigated the relationship between plasma AFP levels and plasma selected miRNA expression levels,and also investigated the correlation of the selected miRNA expression levels and malignant potential.RESULTS Among the five miRNAs selected from the miRNA array results,the expression levels of miR-122-5p were significantly higher in the AFPGC patients than in the non-AFPGC patients(P<0.05).In tissue samples,mi R-122-5p expression level tended to be lower in the non-AFPGC tissue than the normal gastric mucosa.Conversely,in the AFPGC tissue,miR-122-5p expression level was significantly higher in the AFPGC tissue than both the normal gastric mucosa and the nonAFPGC tissue samples(P<0.05).Plasma mi R-122-5p expression levels were also significantly higher in the AFPGC patients than the health volunteers and the nonAFPGC patients(P<0.05)and were strongly correlated with plasma AFP levels(r=0.7975,P<0.0001).Moreover,the correlation of miR-122-5p expression in tissue samples with malignant potential was stronger than that of plasma AFP level in the AFPGC patients.In contrast,no correlation was found between mi R-122-5p expression levels and liver metastasis in the non-AFPGC patients.CONCLUSION miR-122-5p might be a useful biomarker for early detection and disease monitoring in AFPGC.
文摘Although perifollicular repigmentation in the vitiligo lesions is owing to activation of follicular melanocyte stem cells and/or precursor cells followed by supplying matured melanocytes, the underlying mechanism of diffuse repigmentation on the whole vitiligo surface remains still unknown. In addition to the presence of remaining melanocytes, it is conceivable that dermal melanocyte precursor cells contribute to induce diffuse repigmentation after treatment. Therefore, we investigated here whether dermal and follicular melanocyte precursor cells were reduced or not in vitiligo lesions. We performed an immunostaining for Nestin and p75NGFR as dermal melanocyte precursor cells and MITF/Fzd4 as follicular melanocyte precursor cells and compared the positive cells number between lesions and non-lesions (n = 11). Although MITF<sup>+</sup>/Fzd4<sup>+</sup> cells in the hair follicle were significantly decreased in number in the lesions, Nestin<sup>+</sup> and p75NGFR<sup>+</sup> cells were not. This result indicates that dermal precursor cells could be retained in the vitiligo lesions but be disturbed to differentiate into matured melanocytes.
文摘BACKGROUND Recent advancements in biliary tract cancer(BTC)treatment have expanded beyond surgery to include adjuvant therapy,yet the prognosis remains poor.Identifying prognostic biomarkers could enhance the assessment of patients who have undergone radical resection for BTC.AIM To determine transmembrane serine protease 4(TMPRSS4)utility as a prognostic biomarker of radical resection for BTC.METHODS Medical records of patients who underwent radical resection for BTC,excluding intrahepatic cholangiocarcinoma,were retrospectively reviewed.The associations between TMPRSS4 expression and clinicopathological factors,overall survival,and recurrence-free survival were analyzed.RESULTS Among the 85 patients undergoing radical resection for BTC,46(54%)were TMPRSS4-positive.The TMPRSS4-positive group exhibited significantly higher preoperative carbohydrate antigen 19-9(CA19-9)values and greater lymphatic invasion than the TMPRSS4-negative group(P=0.019 and 0.039,respectively).Postoperative overall survival and recurrence-free survival were significantly worse in the TMPRSS4-positive group(median survival time:25.3 months vs not reached,P<0.001;median survival time:28.7 months vs not reached,P=0.043,respectively).Multivariate overall survival analysis indicated TMPRSS4 positivity,pT3/T4,and resection status R1 were independently associated with poor prognosis(P=0.032,0.035 and 0.030,respectively).TMPRSS4 positivity correlated with preoperative CA19-9 values≥37 U/mL and pathological tumor size≥30 mm(P=0.016 and 0.038,respectively).CONCLUSION TMPRSS4 is a potential prognostic biomarker of radical resection for BTC.
基金supported in part by the JSPS-CAS Core-University Program in the field of Plasma and Nuclear Fusion
文摘A long-pulse plasma discharge for more than 30 min. was achieved on the Large Helical Device （LHD）. A plasma of ne = 0.8 × 10^19 m^-3 and T10 = 2.0 keV was sustained with PICH = 0.52 MW, PECH = 0.1 MW and averaged PNBI = 0.067 MW. Total injected heating energy was 1.3 G J, which was a quarter of the prepared RF heating energy. One of the keys to the success of the experiment was a dispersion of the local plasma heat load to divertors, accomplished by shifting the magnetic axis inward and outward.
文摘A CO<sub>2</sub> capture system without supercritical CO<sub>2</sub> was optimized for mixtures of hydrophobic room temperature ionic liquids (RTILs) and propanol. We tested RTILs using bis(trifluoromethanesulfonyl)imide, TFSI-, anion and four quaternary ammonium cations, two quaternary phosphonium cations, and one imidazolium cation. The addition of 2-propanol into the RTILs clearly promoted the capture of normal CO<sub>2</sub>(nCO<sub>2</sub>) at ambient temperature and pressure. When combined with 2-propanol, the most efficient RTILs for nCO<sub>2</sub> capture were N-butyl-N,N,N-trimethylammonium TFSI-. This enhancement of nCO<sub>2</sub> capture was not observed in RTIL mixtures with 1-propanol or in propanol mixtures containing other phosphonium- and imidazolium-based RTILs. The torsion angle of TFSI-, which was calculated using density functional theory, is thought to be related to high nCO<sub>2</sub> capture efficiently.
基金This study was supported in part by funds from a breast cancer advocacy group,100 Voices of Hope(H.Y.)the Indiana University Precision Health Initiative(H.N.)NIH R01AR52144(H.Y.),R03CA238555(H.Y.),and R01AR053237(A.R.).
文摘Osteocytes are the most abundant cells in bone,which is a frequent site of breast cancer metastasis.Here,we focused on Wnt signaling and evaluated tumor-osteocyte interactions.In animal experiments,mammary tumor cells were inoculated into the mammary fat pad and tibia.The role of Lrp5-mediated Wnt signaling was examined by overexpressing and silencing Lrp5 in osteocytes and establishing a conditional knockout mouse model.The results revealed that administration of osteocytes or their conditioned medium(CM)inhibited tumor progression and osteolysis.Osteocytes overexpressing Lrp5 or β-catenin displayed strikingly elevated tumor-suppressive activity,accompanied by downregulation of tumor-promoting chemokines and upregulation of apoptosis-inducing and tumor-suppressing proteins such as p53.The antitumor effect was also observed with osteocyte-derived CM that was pretreated with a Wnt-activating compound.Notably,silencing Lrp5 in tumors inhibited tumor progression,while silencing Lrp5 in osteocytes in conditional knockout mice promoted tumor progression.Osteocytes exhibited elevated Lrp5 expression in response to tumor cells,implying that osteocytes protect bone through canonical Wnt signaling.Thus,our results suggest that the Lrp5/β-catenin axis activates tumor-promoting signaling in tumor cells but tumor-suppressive signaling in osteocytes.We envision that osteocytes with Wnt activation potentially offer a novel cell-based therapy for breast cancer and osteolytic bone metastasis.
基金supported by the Japan Society for the Promotion of Science KAKENHI(contract grant numbers:20H04549,19K12822).
文摘A quantitative analysis method of CO_(2) laser treatments promotes laser treatment performance and rapid clinical application of novel treatment devices.The in silico clinical trial approach,which is based on computational simulation of light-tissue interactions using the mathematical model,can provide quantitative data.Although several simulation methods of laser tissue vaporization with CO_(2) laser treatments have been proposed,validations of the CO_(2) laser wavelength have been insuffcient.In this study,we demonstrated a tissue vaporization simulation using a CO_(2) laser and performed the experimental validation using a hydrogel phantom with constant physical parameters to evaluate the simulation accuracy of the vaporization process.The laser tissue vaporization simulation consists of the calculation of light transport,photothermal conversion,thermal diffusion,and phase change in the tissue.The vaporization width,depth,and area with CO_(2) laser irradiation to a tissue model were simulated.The simulated results differed from the actual vaporization width and depth by approximately 20%and 30%,respectively,because of the solubilization of the hydrogel phantom.Alternatively,the simulation vaporization area for all light irradiation parameters,which is related to the vaporization amount,agreed well with the actual vaporization values.These results suggest that the computational simulation can be used to evaluate the amount of tissue vaporization in the safety and effectiveness analysis of CO_(2) laser treatments.
基金supported in part by funds from the NIH(R01 AR052144 and R03 CA238555 to H.Y.).
文摘Mechanical loading to the bone is known to be beneficial for bone homeostasis and for suppressing tumor-induced osteolysis in the loaded bone.However,whether loading to a weight-bearing hind limb can inhibit distant tumor growth in the brain is unknown.We examined the possibility of bone-to-brain mechanotransduction using a mouse model of a brain tumor by focusing on the response to Lrp5-mediated Wnt signaling and dopamine in tumor cells.The results revealed that loading the tibia with elevated levels of tyrosine hydroxylase,a rate-limiting enzyme in dopamine synthesis,markedly reduced the progression of the brain tumors.The simultaneous application of fluphenazine(FP),an antipsychotic dopamine modulator,enhanced tumor suppression.Dopamine and FP exerted antitumor effects through the dopamine receptors DRD1 and DRD2,respectively.Notably,dopamine downregulated Lrp5 via DRD1 in tumor cells.A cytokine array analysis revealed that the reduction in CCN4 was critical for loading-driven,dopamine-mediated tumor suppression.The silencing of Lrp5 reduced CCN4,and the administration of CCN4 elevated oncogenic genes such as MMP9,Runx2,and Snail.In summary,this study demonstrates that mechanical loading regulates dopaminergic signaling and remotely suppresses brain tumors by inhibiting the Lrp5-CCN4 axis via DRD1,indicating the possibility of developing an adjuvant bone-mediated loading therapy.
文摘The impact of rotavirus (RV) vaccination in reducing severe rotavirus gastroenteritis (RVGE) in outpatient settings was prospectively surveyed in three pediatric clinics in Shibata City. In children younger than 3 years of age, the occurrence of severe RVGE among all acute gastroenteritis (AGE) was found to be significantly lower in three seasons after introduction of RV vaccines, compared to that in 2011, before introduction of RV vaccines. The incidence rates of severe RVGE among children younger than 3 years of age were found to be reduced by 71.2%, 47.7%, and 81.1% for 2012, 2013, and 2014, respectively, compared to that in 2011. These results suggest that the RV vaccination is effective for the prevention of severe RVGE in Japanese voluntary RV vaccination settings with estimated coverage rates of 32.5%, 40.5% and 47.1% for 2012, 2013 and 2014, respectively. It is expected that the reducing effect on severe RVGE would be persistently established by increasing the vaccine coverage rates.
