Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 528
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Intern Med ; 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32581173

RESUMO

We report a 71-year-old man with non-B non-C chronic liver damage who had been regularly visiting our hospital since he was 38 years of age. He underwent three partial hepatectomies for HCC diagnosed at 65, 67, and 71 years of age, respectively. A histopathological examination showed moderately-differentiated HCC, and chronic hepatitis with mild fibrosis stage in non-tumor areas. AFP and PIVKAII were not useful for the early prediction of HCC, but TERT promotor mutation (C228T) in serum cell-free DNA was useful. This is the first report on the importance of long-term follow-up in non-B non-C chronic liver damage, regardless of the fibrosis stage.

2.
Intern Med ; 59(12): 1519-1524, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32536678

RESUMO

A 53-year-old man presented with fulminant hepatitis due to de novo hepatitis B. He had been diagnosed previously with adult T-cell leukemia (ATL) and previously resolved hepatitis B virus infection. The ATL had been treated with cord blood transplantation (CBT). He developed fulminant hepatitis 18 months after CBT, 15 months after the withdrawal of immunosuppressants, and 10 months after vitreous injections of methotrexate for ATL-related retinal infiltration. The aggressive medical protocol included entecavir, prednisolone, plasma exchange, hemodialysis, and bilirubin adsorption. We herein report successful medical treatment for fulminant de novo hepatitis B in a patient considered unsuitable for liver transplantation.

3.
Intern Med ; 2020 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-32448832

RESUMO

Objective The aim of this study was to determine the long-term effects of an SGLT2 inhibitor (SGLT2i) in NAFLD patients with type 2 diabetes mellitus (T2DM) on the clinical features and liver histopathology. Methods In this retrospective study, the long-term histological impacts of SGLT2i in NAFLD patients with T2DM were investigated. Patients or Materials Seven patients with NAFLD and T2DM were treated for the long term with 100 mg/day canagliflozin, an SGLT2i, and liver biopsies were obtained at the 3 points of pretreatment, 24 weeks, and ≥1 year (third liver biopsy) after the start of treatment. Six of seven patients were evaluated with third liver biopsy at the point of three or more years. The primary outcome was liver histopathological changes (defined as a decrease in the NAFLD activity score of one point or more without worsening of the fibrosis stage, compared to pretreatment). Results All 7 patients showed worsening of body mass index and waist circumference at the third liver biopsy compared to 24 weeks. However, the scores of steatosis, lobular inflammation, ballooning, and fibrosis stage improved at the third liver biopsy in 57%, 43%, 14%, and 29% of the patients, respectively, compared to pretreatment. One of the seven patients showed histopathological worsening at the third liver biopsy compared to pretreatment, but the improvement was maintained in the other six patients. Conclusion The long-term treatment of NAFLD complicated by T2DM using an SGLT2i is associated with long-term improvement in liver histopathology despite the worsening of clinical features.

4.
Gastric Cancer ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32367440

RESUMO

BACKGROUND: Gastric cancer (GC) patients with PD-L1-negative tumor occasionally have a favorable response to anti-PD-1 mAb. The aim of the present study was to investigate the regulatory mechanism and immunosuppressive role of PD-L2 in GC. METHODS: We used immunohistochemistry to evaluate the expression of PD-L2 in primary tumors from 194 patients with GC. The mechanism of PD-L2 expression was assessed in TCGA stomach adenocarcinoma tissue dataset and in vitro assay using GC cell lines. The immunosuppressive role of PD-L2 was evaluated by cytotoxicity of CTL clone against PD-L2 expressing GC cells. RESULTS: PD-L2 was expressed on tumor cells (TCs) of 28.4% patients and PD-L2 expression on TCs was significantly associated with tumor progression. TCGA dataset revealed that IFN-γ and, to a lesser extent, IL-4 signature significantly correlated with PD-L2 expression. In vitro assay showed that IFN-γ and, also to a lesser extent, IL-4 can upregulate PD-L2 expression on GC cells. Anti-PD-L2 mAb significantly enhanced the cytotoxicity of CTL clone against GC cell lines expressing PD-L2. CONCLUSIONS: PD-L2 is expressed on GC cells and PD-1/PD-L2 interaction are functionally involved in anti-tumor CTL activities. PD-L2 expression should be considered when determining the optimal immunotherapy for GC.

5.
Med Mol Morphol ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32410010

RESUMO

Histopathology is essential for the diagnosis and evaluation of disease activity of autoimmune hepatitis (AIH). We aimed to elucidate the characteristics of AIH from the localization of inflammation. We re-evaluated a nationwide survey that was performed in Japan in 2018 of AIH patients diagnosed between 2014 and 2017. A total of 303 patients were enrolled, and the clinical and treatment characteristics were compared between the patients with predominantly portal inflammation (230 patients) or lobular inflammation (73 patients). AIH patients with lobular inflammation had a higher probability of being diagnosed with acute hepatitis than those with portal inflammation. Liver enzyme levels were higher in patients with lobular inflammation, whereas immunoglobulin G levels were higher in patients with portal inflammation. The prevalence of an alanine aminotransferase level < 30 U/L after 6 months of treatment was significantly higher in patients with lobular inflammation than in those with portal inflammation (81.7% vs. 67.3%, P = 0.046). The localization of inflammation may be useful for evaluating the onset of AIH.

6.
Curr Microbiol ; 77(8): 1506-1517, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32239288

RESUMO

The secretome of Trichoderma reesei contains a mixture of cellulases, hemicellulases, amylases, proteases, and lipases that synergistically degrade plant biomass. Trichodermapepsin (TrAsP), the most prominent protease of T. reesei, affects the stability of cellulases. Similar to cellulase production, TrAsP production also depends on carbon and nitrogen sources. Unlike the cellulase mechanism, the regulatory mechanism of TrAsP remains unknown. Therefore, this study aimed to determine the effect of the main cellulase regulator Xyr1 and nitrogen regulator Are1 on trasp regulation. Cellulase inducer Avicel and TrAsP inducer galactose were used as carbon sources. qRT-PCR analysis revealed that Xyr1 and Are1 acted as a repressor and an activator for trasp expression, respectively. Compared to Avicel, relative expression was higher in galactose. The binding motifs of Xyr1 and Are1 were located in upstream of the trasp promoter. From promoter deletant analysis using the ß-glucuronidase reporter gene, the area from - 870 bp to - 670 bp was identified as the only region for positive regulation and there were both binding motifs of Xyr1 and Are1. Reporter assay of mutants confirmed functions of downregulation of Xyr1 and upregulation of Are1. Electrophoretic mobility shift assay demonstrated the binding ability of Xyr1 and Are1 to the particular binding motifs and their functionality was confirmed. Further, this study demonstrated that Cre1, Xpp1, and Pac1 downregulate trasp expression similar to that in cellulase regulation mechanism. These results demonstrate that transcriptional regulators of cellulase control trasp expression and suggest the possibility of the existence of specific protease regulators in T. reesei.

7.
Biosci Biotechnol Biochem ; 84(7): 1501-1512, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32189572

RESUMO

The oleaginous yeast Rhodosporodium toruloides is receiving widespread attention as an alternative energy source for biofuels due to its unicellular nature, high growth rate and because it can be fermented on a large-scale. In this study, R. toruloides was cultured under both light and dark conditions in order to understand the light response involved in lipid and carotenoid biosynthesis. Our results from phenotype and gene expression analysis showed that R. toruloides responded to light by producing darker pigmentation with an associated increase in carotenoid production. Whilst there was no observable difference in lipid production, slight changes in the fatty acid composition were recorded. Furthermore, a two-step response was found in three genes (GGPSI, CAR1, and CAR2) under light conditions and the expression of the gene encoding the photoreceptor CRY1 was similarly affected.

8.
Ann Nucl Med ; 34(5): 349-357, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32166712

RESUMO

OBJECTIVE: Gamma camera-based measurement of glomerular filtration rate (GFR) with 99mTc-diethylenetriaminepentaacetic acid (DTPA) is an established non-invasive measurement of split renal function; however, it is not as accurate as the plasma sample method. Therefore, study into improving the accuracy of such method is clinically relevant. The aim of this study was to elucidate the feasibility of gamma camera-based GFR measurement using renal depth evaluated by lateral scan of 99mTc-DTPA renography and comparing the results with those of GFR using renal depth measured by CT, and three representative formulas. METHODS: The study population comprised 38 patients (median, 69 years; male 28, female 10; median estimated GFR, 67.4 ml/min) with renourinary disorders. Scintigraphy was performed after intravenous injection of 370 MBq 99mTc-DTPA by dynamic data acquisition for 20 min, followed by a bilateral static scan of the abdomen for 3 min. All patients underwent computed tomography (CT) within 2 months from renography. GFR was calculated by renography using renal depth determined in five ways; lateral scan of 99mTc-DTPA, CT, and three formulas previously created with using weight, height and age. GFRs were compared with estimated GFR (eGFR). The depth of both kidneys measured as described above was compared and evaluated the laterality of the renal depth. RESULTS: The median values of GFR calculated with renal depth determined by 99mTc-DTPA renography, CT, and the three formulas were 87.3, 83.9, 67.8, 68.3, and 71.5 ml/min, respectively. All of them correlated significantly with eGFR (r = 0.734, r = 0.687, r = 0.728, r = 0.726, and r = 0.686, respectively), however, no significant difference was observed among five correlation coefficients. Bland-Altman plot revealed that eGFR had error and fixed bias when compared with GFRs calculated using renal depth determined by renography, CT, and Taylor's formula. The depth of both kidneys measured by 99mTc-DTPA renography was equivalent to that measured by CT, however, those measured by the three formulas were significantly smaller than that measured by 99mTc-DTPA renography. The depth of the right kidney was larger than that of the left kidney using all three formulas in all patients. However, CT detected only 66% of patients to have a deeper right kidney than left kidney. CONCLUSION: Lateral scanning is a feasible procedure to measure renal depth for accurate and reasonable split GFR measurements using 99mTc-DTPA renography.

9.
J Med Virol ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32100879

RESUMO

Telomerase reverse transcriptase (TERT) promoter mutation is the most frequent genetic alteration in hepatocellular carcinoma (HCC). However, there is currently no suitable highly sensitive method that can detect such mutation using serum cell-free DNA (cfDNA). We analyzed somatic point mutations that substitute cytosine for thymidine at position 228 (C228T), as one of the hotspots of TERT promoter mutations, in serum cfDNA using a highly sensitive detection method of wild-type blocking polymerase chain reaction (WTB-PCR) combined with Sanger sequencing. In TERT promoter mutation sensitivity study, synthetic oligonucleotides were prepared to determine the lowest detection limit of the WTB-PCR, using serial dilutions of mutant-type (MT) DNA in the background of wild-type (WT) DNA. Using this technique, we conducted a longitudinal study in one patient who developed HCC during the follow-up and determined the relationship between HCC and TERT C228T in serum cfDNA. In the sensitivity study, the mutant peak at position 228 was detected at 0.7% or higher but was not detected at 0.6%. Thus, sequencing analysis of WTB-PCR product demonstrated the limit of detection in excess of 0.7% MT DNA in the background of WT DNA. One male patient with HCV-related cirrhosis developed HCC during the follow-up. TERT C228T was negative before the diagnosis of HCC, positive at the diagnosis of HCC and did not increase with advancement of malignancy. We developed a highly sensitive method for detection of TERT promoter mutation using WTB-PCR combined with Sanger sequencing and demonstrated its clinical usefulness in the measurement of TERT C228T in serum cfDNA. Larger studies are needed to confirm these results and establish the clinical utility of this new method.

10.
J Gastrointest Surg ; 24(1): 50-57, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31190124

RESUMO

PURPOSE: This study sought to investigate the clinical impact of repeated interventions for recurrent hepatocellular carcinoma (HCC) and to establish a new surrogate measure for survival: the time-to-interventional failure (TIF). METHODS: Based on a retrospective review of 1158 patients who underwent curative resection for HCC, the abilities of recurrence-free survival (RFS) and TIF, which was defined as the elapsed time from resection to unresectable/unablatable recurrence, to predict overall survival (OS) were compared. RESULTS: Within a median follow-up period of 84.9 months, 676 (59.0%) recurrence events occurred, 78.1% of which were resectable/ablatable recurrences. Of these, 99.1% of the patients underwent repeated treatments. TIF had a stronger correlation than RFS (r = 0.921 vs. r = 0.631) in prediction of OS. Patients who underwent curative-intent treatment (i.e., resection or ablation) for recurrence showed significantly better survival outcomes compared with those who underwent non-curative treatment (e.g., TACE, chemotherapy) (median OS, 89.1 months vs. 55.0 months; P < 0.0001). This tendency was constant across the AJCC stages and multivariate analysis confirmed that curative-intent treatment is associated with improved survival after initial recurrence (hazard ratio, 0.55; 95% CI, 0.37-0.81; P = 0.003). CONCLUSIONS: OS after HCC resection is more strongly dependent on TIF than on RFS. Aggressive curative-intent interventions for recurrent HCC may prolong survival regardless of the cancer stage.

11.
Intern Med ; 59(3): 365-372, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31619599

RESUMO

We herein report a 48-year-old healthy woman who visited our hospital to investigate a 25-mm space-occupying lesion in the liver. The tumor was irregularly shaped and exhibited heterogeneous enhancement on dynamic computed tomography (CT). Whole-body positron emission tomography-CT showed an abnormal fluorodeoxyglucose uptake in the liver tumor, with a maximum standardized uptake value of 12.82. During the ensuing three months, the tumor grew rapidly and the serum alpha-fetoprotein levels also rose; partial hepatectomy was therefore performed. Microscopic findings revealed a moderately-to-poorly differentiated hepatocellular carcinoma in the normal liver.

12.
Phys Med Biol ; 65(5): 05LT01, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-31323647

RESUMO

The Compton camera can simultaneously acquire images of multiple isotopes injected in a body; therefore, it has the potential to introduce a new subfield in the field of biomedical imaging applications. The objective of this study is to assess the ability of a prototype semiconductor-based silicon/cadmium telluride (Si/CdTe) Compton camera to simultaneously image the distributions of technetium (99mTc)-dimercaptosuccinic acid (DMSA) (141 keV emission) and 18F-fluorodeoxyglucose (FDG) (511 keV emission) injected into a human volunteer. 99mTc-DMSA and 18F-FDG were injected intravenously into a 25-year-old male volunteer. The distributions of 99mTc-DMSA and 18F-FDG were simultaneously made visible by setting a specified energy window for each radioisotope. The images of these radiopharmaceuticals acquired using the prototype Compton camera were superimposed onto computed tomography images for reference. The reconstructed image showed that 99mTc-DMSA had accumulated in both kidneys, which is consistent with the well-known diagnostic distribution determined by clinical imaging via single-photon emission computed tomography. In the 18F-FDG image, there is broad distribution around the liver and kidneys, which was expected based on routine clinical positron emission tomography imaging. The current study demonstrated for the first time that the Si/CdTe Compton camera was capable of simultaneously imaging the distributions of two radiopharmaceuticals, 99mTc-DMSA and 18F-FDG, in a human body. These results suggest that the Si/CdTe Compton camera has the potential to become a novel modality for nuclear medical diagnoses enabling multi-probe simultaneous tracking.

13.
Intern Med ; 59(3): 329-338, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31534089

RESUMO

Objective The correlation between the insulin secretion levels and the risk of hepatocarcinogenesis is clinically important. The aim of the present study was to determine the effects of various clinical parameters on C-peptide (CPR) levels in patients with non-alcoholic fatty liver disease (NAFLD). Methods In this retrospective cohort study, the effects of clinical parameters on insulin resistance (HOMA-IR) and insulin secretion levels (HOMA-ß and fasting CPR) were investigated. Patients A total of 244 Japanese patients with histopathologically confirmed NAFLD were evaluated. Of these, 77 underwent the meal tolerance test (MTT) to evaluate the association of various clinical parameters with the CPR levels at 120 minutes. Results A multivariate analysis identified fasting plasma glucose (FPG) (≥110 mg/dL), aspartate aminotransferase (≥1.0×ULN IU/L), and a large waist circumference as independent predictors of insulin resistance (HOMA-IR ≥2.5) or high fasting CPR levels. Significant parameters for a low insulin secretion capacity (HOMA-ß <30%) were not detected, except for the parameters mentioned in the diagnostic criteria of diabetes mellitus. Regarding the MTT, the CPR levels at 120 minutes were significantly higher in patients with fibrosis stage 3-4 than in those with stage 0-2. Body composition and genetic variation did not affect the CPR levels at 120 minutes. A multivariate analysis identified fibrosis stage (3-4), hyperuricemia, FPG (≥110 mg/dL), and procollagen III peptide (>1.0 U/mL) as independent predictors of high CPR levels at 120 minutes. Conclusion The present study showed that high plasma glucose levels and severe liver fibrosis stage influence insulin secretion levels in Japanese patients with NAFLD. Conservation of delayed insulin secretion levels was confirmed in patients with severe liver fibrosis.

14.
Hepatol Res ; 50(4): 426-438, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31785120

RESUMO

AIM: The risk of development of hepatocellular carcinoma (HCC) persisted in patients with advanced fibrosis, even after achieving sustained virologic response (SVR). This study aimed to show the advantage of liver stiffness measurement (LSM) at baseline and after SVR to predict HCC occurrence and esophageal varices (EV) exacerbation. METHODS: These risks were evaluated in 398 chronic hepatitis C patients without a history of HCC who achieved SVR after direct-acting antiviral agent and evaluated LSM at least twice during follow up. We defined liver cirrhosis and chronic hepatitis as LSM of ≥12 kPa and <12 kPa, respectively. RESULTS: LSM was significantly correlated with serum fibrosis markers, such as Fib-4 index and Wisteria floribunda agglutinin-positive Mac-2 binding protein, at baseline and SVR at 24 weeks after treatment (SVR24). Five patients received preventive treatment of EV, but no EV bleeding occurred after SVR, and their LSM at baseline and SVR24 was significantly higher than that of other cirrhosis patients. The annual rate of HCC during the first 4 years was 1.5%. LSM in HCC patients tended to decrease after direct-acting antiviral agent therapies, but significantly higher than that of cirrhosis patients without HCC before and after treatment. Multivariate analysis identified LSM and alpha-fetoprotein at baseline and LSM at SVR24 as significant independent predictors of HCC. CONCLUSIONS: Evaluating LSM not only at baseline, but also SVR24, was found to be useful for the detection of advanced fibrosis patients at high risk of HCC occurrence and EV exacerbation. We recommend focused surveillance of HCC and EV for these patients.

15.
Sci Rep ; 9(1): 13587, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537874

RESUMO

Antimicrobial resistance is a global public threat and raises the need for development of new antibiotics with a novel mode of action. The dipeptidyl peptidase 11 from Porphyromonas gingivalis (PgDPP11) belongs to a new class of serine peptidases, family S46. Because S46 peptidases are not found in mammals, these enzymes are attractive targets for novel antibiotics. However, potent and selective inhibitors of these peptidases have not been developed to date. In this study, a high-resolution crystal structure analysis of PgDPP11 using a space-grown crystal enabled us to identify the binding of citrate ion, which could be regarded as a lead fragment mimicking the binding of a substrate peptide with acidic amino acids, in the S1 subsite. The citrate-based pharmacophore was utilized for in silico inhibitor screening. The screening resulted in an active compound SH-5, the first nonpeptidyl inhibitor of S46 peptidases. SH-5 and a lipophilic analog of SH-5 showed a dose-dependent inhibitory effect against the growth of P. gingivalis. The binding mode of SH-5 was confirmed by crystal structure analysis. Thus, these compounds could be lead structures for the development of selective inhibitors of PgDPP11.

16.
Hepatol Res ; 49(12): 1441-1450, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31373093

RESUMO

AIM: The long-term effects of sustained virologic response (SVR) to antiviral therapy on the risk of liver complications, such as exacerbation of esophageal varices (EV), hepatocellular carcinoma (HCC), malignant lymphoma, and liver-related and overall death in hepatitis C virus (HCV)-infected patients with liver cirrhosis are not fully known. METHODS: These risks were evaluated during long-term follow up of 457 patients with HCV-related Child-Pugh Class A liver cirrhosis without history of HCC. RESULTS: The respective cumulative 5- and 10-year rates of EV exacerbation were 2.0% and 3.1%. Multivariate analysis identified the presence of EVs, thrombocytopenia at baseline. and alcohol intake as significant independent predictors of EV exacerbation before and after SVR. The cumulative 5- and 10-year rates of HCC were 6.8% and 10.2%, respectively. Male sex and the presence of EV were significant independent determinants of HCC before and after SVR. Although the cumulative 5-year HCC recurrence rate was 49.4%, the overall survival rate since HCC was 73.6% at 5 years. The overall survival rates since SVR were 98.7% and 93.6% at 5 and 10 years, respectively. Progression of HCC was the most frequent all-cause mortality, but none of the patients died of liver decompensation. Male sex and Fibrosis-4 index of ≥3.0 after SVR were significant and independent predictors of mortality. CONCLUSION: Patients with HCV remain at risk of HCC for >10 years after achieving SVR, and HCC is the most common cause of mortality. We recommend long-term surveillance of cirrhotic patients with HCV, even after achieving SVR.

17.
Hepatol Res ; 49(12): 1406-1413, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31347756

RESUMO

AIM: Rifaximin (RFX) improves hepatic encephalopathy (HE). However, information on long-term treatment with RFX is limited. In this study, we aimed to investigate the effect of long-term treatment with RFX on HE and liver function. Moreover, we investigated factors associated with the recurrence of HE under RFX treatment. METHODS: In this retrospective cohort study, we consecutively enrolled 65 patients with HE who initiated RFX treatment (1200 mg/day) in our hospital from January 2017 to June 2018. We evaluated liver function test results, including blood ammonia levels, and the recurrence rate of HE after RFX treatment. RESULTS: The median follow-up duration was 41.6 weeks (range, 1.4-96.7 weeks). The blood ammonia level significantly declined from 157 to 86 µg/dL at 4 weeks after RFX treatment (P < 0.01), and the effect was prolonged. Furthermore, Child-Pugh score decreased in 51% (26/51) of the patients at 12 weeks during RFX treatment. The recurrence rate of HE after RFX treatment was 26.2% (17/65), and presence of ascites at baseline was identified as the only independent risk factor for HE recurrence (hazard ratio 4.71; 95% confidence interval, 1.27-17.5; P = 0.02). The cumulative recurrence rate of HE was significantly lower in patients without ascites than in patients with ascites at baseline (13.8% vs. 50.8%, P = 0.001). CONCLUSIONS: Long-term treatment with RFX was beneficial for HE and liver function in patients with HE. Furthermore, the recurrence rate of HE was low in RFX-treated patients without ascites. Thus, long-term treatment with RFX could be effective for the management of Japanese patients with HE.

18.
Gan To Kagaku Ryoho ; 46(5): 845-849, 2019 May.
Artigo em Japonês | MEDLINE | ID: mdl-31189801

RESUMO

The combination treatment of radiotherapy with anti-PD-1/PD-L1 antibody has been shown to significantly improve the clinical outcome of various cancers. Recent studies showthat radiotherapy has multiple functions in modifying the tumor microenvironment, by inducing both immunostimulation and immunosuppression. The upregulation of PD-L1 expression in cancer cells interferes with the effector functions of interacting T cells. Preclinical studies demonstrate that radiotherapy induces PD-L1 upregulation by 4 pathways; (1)IFN-γ signaling,(2)EGFR pathway,(3)DNA damage signaling pathway, and(4)cGAS-STING pathway. All of these mechanisms are involved in the upregulation of PD-L1 expression in cancer cells via JAK/STAT pathway. Because the PD-1/PD-L1 interaction has been shown to be one of the major mechanisms of cancer immune escape, which leads to treatment failure, anti-PD-1/PD-L1 antibody may improve the efficacy of radiotherapy by enhancement of anti-tumor activity. In addition, PD-L1 expression is one of the biomarkers of good response to anti-PD-1/ PD-L1 antibody. Therefore, the comprehensive understanding of the mechanism underlying PD-L1 expression in response to radiotherapy is important for the establishment of optimal combination strategy. This approach could help to provide the basis for the combined therapies and promote personalized immuno-radiotherapy, although the signaling of PD-L1 upregulation induced by radiotherapy in tumors could be intricately regulated. In this article, we review previous researches which revealed the mechanisms of PD-L1 upregulation induced by radiotherapy.


Assuntos
Neoplasias/radioterapia , Antígeno B7-H1 , Humanos , Interferon gama , Transdução de Sinais , Regulação para Cima
19.
Intern Med ; 58(18): 2657-2662, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31178495

RESUMO

We experienced two cases of hepatitis C virus (HCV) eradication failure in patients with a history of non-responsiveness to previous treatments with direct-acting antiviral agents (DAAs) who were subsequently treated with the combination of glecaprevir and pibrentasvir (GLE/PIB). Direct sequencing at commencement of GLE/PIB therapy showed non-structural protein (NS) 5A-P32 deletion in the first patient and NS5A-R30E/Q54H/A92K in the second patient (both genotype 1b). The common point was that L31/Y93 was double wild-type, and the IL28B polymorphism was non-TT type. Even when L31/Y93 is double wild-type, other NS5A mutations may affect the DAA re-treatment outcome. We analyzed the transition of amino acid mutations at NS5A by ultra-deep sequencing.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Hepatite C Crônica , Interferons/genética , Quinoxalinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Feminino , Genótipo , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Humanos , Polimorfismo Genético
20.
Cancer Sci ; 110(7): 2156-2165, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31099450

RESUMO

The incidence of colorectal cancer (CRC) has been on the rise, which is linked to the increasing prevalence of obesity, based on global epidemiological evidence. Although chronic inflammation is implicated in tumor development, the mechanisms underlying obesity-associated CRC remain unknown. Here, we sought to identify the inflammatory cytokines and their roles in obesity-related colorectal tumorigenesis using cytokine array analyses in a mouse model. Colorectal tumorigenesis was induced through i.p. injection of azoxymethane once a week for 6 weeks in 6-week-old female WT C57Black/6J mice and the obesity diabetes model mouse KK/TaJcl, KK-Ay/TaJcl. The formation of aberrant crypt foci and colorectal tumors were more frequent in obese mice compared with WT mice, and both serum interleukin (IL)-13 and IL-13 receptor (R) expression in the normal intestinal mucosal epithelium were significantly increased in the obese mice. Furthermore, addition of IL-13 to a human CRC cell line and a human colon organoid culture altered the phenotype of intestinal epithelial cells. Knockdown experiments further revealed that IL-13Rα1 dominantly induced mucosal proliferation. Collectively, These results suggest an association between anti-inflammatory cytokines and colorectal carcinogenesis, and provide new research directions for cancer prevention strategies. In particular, inflammation provoked by obesity, notably by increased expression of the cytokine IL-13, could play an important role in the carcinogenesis of obesity-related CRC.


Assuntos
Focos de Criptas Aberrantes/patologia , Azoximetano/efeitos adversos , Neoplasias Colorretais/patologia , Interleucina-13/sangue , Obesidade/complicações , Regulação para Cima , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/metabolismo , Animais , Azoximetano/administração & dosagem , Proliferação de Células , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/imunologia , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/imunologia , Absorção Peritoneal , Receptores de Interleucina-13/sangue , Transdução de Sinais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA