Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 68
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Mol Ther ; 31(7): 2077-2088, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37060176

RESUMO

OBP-301 is an oncolytic adenovirus modified to replicate within cancer cells and lyse them. This open-label, non-comparative, phase I dose-escalation trial aimed to assess its safety and optimal dosage in 20 patients with advanced hepatocellular carcinoma. Good tolerance was shown with a maximum tolerated dose of 6 × 1012 viral particles. The most common treatment-emergent adverse events were influenza-like illness, pyrexia, fatigue, decreased platelet count, abdominal distension, and anemia. Cohorts 4 and 5 had approximately 50% higher levels of CD8+ T cells in the peripheral blood after injection. The best target response occurred in 14 patients, 4 of whom had progressive disease. Multiple intratumoral injections of OBP-301 were well tolerated in patients with advanced hepatocellular carcinoma. The stable disease rate for the injected tumors was greater than the overall response rate, even with no obvious tumor response. OBP-301 might have a greater impact on local response as histological examination revealed that the presence of OBP-301 was consistent with the necrotic area at the injection site. Increased infiltration of CD8+ T cells and <1% PD-L1 expression were observed in tumors after injection. Improved antitumor efficacy might be achieved in future studies via viral injection with volume adjustment and in combination with other immuno-therapeutics.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Terapia Viral Oncolítica , Vírus Oncolíticos , Telomerase , Humanos , Adenoviridae/genética , Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Linhagem Celular Tumoral , Terapia Viral Oncolítica/efeitos adversos , Vírus Oncolíticos/genética
2.
Stem Cells ; 40(11): 1031-1042, 2022 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-35922037

RESUMO

Myogenic progenitors (MPs) generate myocytes that fuse to form myofibers during skeletal muscle development while maintaining the progenitor pool, which is crucial for generating sufficient muscle. Notch signaling has been known to reserve a population of embryonic MPs during primary myogenesis by promoting cell cycle exit and suppressing premature differentiation. However, the roles of individual Notch receptors (Notch1-4) during embryonic/fetal myogenesis are still elusive. In this study, we found that Notch1 and Notch2, which exhibit the highest structural similarity among Notch receptors, maintain the MP population by distinct mechanisms: Notch1 induces cell cycle exit and Notch2 suppresses premature differentiation. Moreover, genetic and cell culture studies showed that Notch1 and Notch2 signaling in MPs are distinctively activated by interacting with Notch ligand-expressing myofibers and MP-lineage cells, respectively. These results suggest that through different activation modes, Notch1 and Notch2 distinctively and cooperatively maintain MP population during fetal myogenesis for proper muscle development.


Assuntos
Desenvolvimento Muscular , Receptor Notch1 , Receptor Notch1/genética , Receptor Notch1/metabolismo , Desenvolvimento Muscular/genética , Transdução de Sinais/fisiologia , Diferenciação Celular/genética , Receptores Notch
3.
J Korean Med Sci ; 38(34): e270, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37644684

RESUMO

BACKGROUND: This study aimed to investigate the prevalence rate of hepatitis C virus (HCV) infection and identify the demographic, and sociological characteristics and changes in awareness of HCV infection by participating the study for North Korean defectors residing in South Korea. METHODS: This study prospectively enrolled participants. Demographic, sociological and clinical data, and questionnaire surveys focused on awareness of HCV infection were collected. RESULTS: In total, 211 North Korean defectors participated in this study from September 2020 until June 2021. There were 174 women (82.5%), and the overall mean age was 48.9 years (range, 20 to 80 years). Of these participants, 112 (53.1%) had immigrated to South Korea since 2011. The overall prevalence of anti-HCV antibody among North Korean defectors was 1.9%. Thirty participants (14.2%) had hepatitis B surface antigens. A huge lack of awareness regarding HCV infection has been observed among North Korean defectors. CONCLUSION: This is the first prospective study to investigate the prevalence rate of HCV infection among North Korean defectors residing in South Korea. As North Korean defectors are a vulnerable group concerning HCV infection, they may benefit from HCV screening policies and educational interventions for HCV infection.


Assuntos
Hepacivirus , Hepatite C , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , República Democrática Popular da Coreia/epidemiologia , Estudos Prospectivos , Hepatite C/epidemiologia , República da Coreia/epidemiologia
4.
J Korean Med Sci ; 38(38): e340, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37750375

RESUMO

This corrects the article on p. e270 in vol. 38, PMID: 37644684.

5.
Molecules ; 26(2)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33435572

RESUMO

The high rates of hepatocellular carcinoma (HCC) recurrence after initially successful curative therapy emphasize ongoing unmet needs to prevent or reduce HCC recurrence. Retinoid acid (RA), a metabolite of vitamin A and its related analogues (termed retinoids) has been suggested as a promising chemotherapeutic agent in cancer treatment. The synthetic oral retinoid peretinoin is the only agent for the secondary chemoprevention of HCC after curative therapy that is currently well applied into clinical development. Here we present an updated summary of the molecular pathogenesis of HCC and of preclinical and clinical findings with peretinoin, including its clinical characteristics, safety and tolerability profile and future perspectives for clinical use.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Retinoides/uso terapêutico , Animais , Humanos
6.
Clin Gastroenterol Hepatol ; 16(12): 1954-1963.e3, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29753085

RESUMO

BACKGROUND & AIMS: Little is known about the effects of antiviral therapy on short- and long-term survival of patients with hepatitis B virus (HBV)-related decompensated cirrhosis. We aimed to determine whether a maintained virologic response (MVR, defined as persistent undetectable HBV DNA during therapy) associates with short-term (6 mo) and long-term (6-120 mo) survival of patients with decompensated cirrhosis. METHODS: We performed a 10-year observation analysis using data from the Epidemiology and Natural History of Liver Cirrhosis study of patients with decompensated liver cirrhosis in Korea. Of the entire cohort (1595 patients enrolled at onset of decompensation since 2005), our analysis comprised 295 patients who immediately began treatment with entecavir (n = 179) or lamivudine (n = 116) after decompensation. We collected laboratory test results, data on hepatocellular carcinoma (HCC) development, and Child-Turcotte-Pugh and model for end-stage liver disease (MELD) scores. The mean follow-up time was 62.3 ± 36.5 months. The primary end point was time of liver transplant-free survival. RESULTS: The median survival time was 7.7 years; 60.1% of patients survived for 5 years and 45.7% survived for 10 years without liver transplantation. An MVR was observed in 116 patients (39.3%); these patients had significantly longer times of transplant-free survival than patients without MVR. Survival times associated with the occurrence of HCC; survival of patients without HCC was excellent if they survived the first 6 months after initiation of antiviral therapy, whereas the survival rates of patients with HCC decreased persistently over time. A baseline MELD score above 20 and multiple complications were associated with short-term mortality. MVR was the factor most strongly associated with long-term transplant-free survival. Significantly higher proportions of patients who received entecavir survived 10 years compared with patients who received lamivudine, but no difference was observed among patients with MVRs. Patients with MVRs had significant improvement in hepatic function over time, but nonsignificant reductions in risk of HCC or HCC-related mortality. CONCLUSIONS: In a 10-year observation study of patients in Korea with HBV-related decompensated cirrhosis, we found baseline MELD score and MVR to entecavir or lamivudine to associate with short- and long-term transplant-free survival. The benefits of an MVR are maintained for up to 10 years even after decompensation, but patients are still at risk for HCC.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Falência Hepática/tratamento farmacológico , Falência Hepática/patologia , Resposta Viral Sustentada , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Humanos , Coreia (Geográfico) , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
7.
Hepatol Res ; 47(5): 387-397, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27272116

RESUMO

AIM: The aim of this study was to investigate the effect of yttrium-90 radioembolization on the outcome of Asian patients with early to advanced stage hepatocellular carcinoma (HCC). METHODS: Sixty-two patients were screened and 50 patients (80.6%) were eligible. Response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST), and overall survival was estimated using the Kaplan-Meier method. RESULTS: The Barcelona Clinic Liver Cancer (BCLC) stage was A in 40% of patients, B in 24%, and C in 36%; 66% of patients had hepatitis B virus infections. According to RECIST criteria, partial responses occurred in 40% of patients, and stable disease was achieved in 46%. Tumor response was significantly associated with BCLC stage (P = 0.003). The median overall time to progression was 5.8 months (range, 0.9-46.1 months). Follow-up treatments after radioembolization were carried out in 31 patients due to remnant HCC (n = 18) or HCC progression (n = 13). The median overall survival was 40.9 months (95% confidence interval, 10.2-71.6 months). Treatment was tolerable except for one lung toxicity and two hepatic toxicities. CONCLUSION: Yttrium-90 radioembolization appears to be well tolerated and effective in Asian patients with BCLC stage A-C HCC. Follow-up treatments after radioembolization can be safely provided.

8.
Mediators Inflamm ; 2017: 5198798, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28512387

RESUMO

Hepatocellular carcinoma is highly refractory cancer which is resistant to conventional chemotherapy and radiotherapy, carrying a dismal prognosis. Although many anticancer drugs have been developed for treating HCC, sorafenib is the only effective treatment, but it only prolongs survival duration for about 3 months. Recently, oncolytic virotherapy has shown promising results in treating HCCs and the effects can be more enhanced by adopting immune modulatory molecules. This review discusses the current status of treating HCC and the effective strategy of oncolytic virus-based immunotherapy for the treatment of HCCs.


Assuntos
Carcinoma Hepatocelular/terapia , Imunoterapia/métodos , Neoplasias Hepáticas/terapia , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/fisiologia , Compostos de Fenilureia/uso terapêutico , Sorafenibe
9.
Hepatology ; 61(6): 1809-20, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25627342

RESUMO

UNLABELLED: The effect of viral suppression on long-term disease outcome after decompensation in patients with hepatitis B virus (HBV)-related cirrhosis has not been established. The aim of this study was to determine the long-term effect of antiviral therapy (AVT) in patients with HBV-related decompensated cirrhosis. This was a multicenter, prospective, inception cohort study of 707 patients who presented with first-onset decompensated complications, including 284 untreated and 423 antiviral-treated patients (58 previously treated, 253 with early treatment, and 112 with delayed treatment). The primary endpoint was 5-year liver transplantation (LT)-free survival. Secondary endpoints included virological response (VR) and serological response and improvement in liver function. Despite baseline high HBV activity and worse liver function, antiviral-treated patients had significantly better transplant-free survival than untreated patients (5-year survival rates of 59.7% vs. 46.0%, respectively), with more apparent benefits from antivirals in Child-Turcotte-Pugh class B/C and high-viremia groups. The rate of VR and hepatitis B e antigen seroconversion at 5 years in antiviral-treated patients was 14.2% and 49.1%, respectively. A significant improvement in liver function was observed in treated versus untreated patients, with 33.9% of treated patients delisted for LT. Patients with early treatment had better clinical outcomes than those with delayed treatment. Survival was dependent on antiviral response, being significantly better in responders than in nonresponders or untreated cases. The initial benefit of AVT was negated over time in nonresponders. Antiviral treatment and maintained VR remained independently predictive of survival. The study results were corroborated by propensity score-matching analysis. CONCLUSION: AVT significantly modifies the natural history of decompensated cirrhosis, improving liver function and increasing survival. The results underscore the importance of promptly administering potent antiviral drugs to patients under consideration for LT.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/virologia , Adulto , Idoso , Feminino , Hepatite B Crônica/sangue , Humanos , Cirrose Hepática/mortalidade , Testes de Função Hepática , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Prospectivos , República da Coreia/epidemiologia
10.
J Gastroenterol Hepatol ; 31(4): 865-71, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26572068

RESUMO

BACKGROUND AND AIM: There are limited data assessing whether patients who achieved virological suppression on lamivudine but remain hepatitis B "e" antigen-positive should be switched to a more potent antiviral with a high genetic barrier to resistance or continue with lamivudine. We compared the safety and efficacy of switching with entecavir versus continuing lamivudine. METHODS: This was a Phase IV, randomized, open-label, prospective study in a tertiary care setting. Seventy-three chronic hepatitis B patients who achieved virological suppression on lamivudine (serum hepatitis B virus DNA < 60 International Unit (IU)/mL) were enrolled. Entecavir or lamivudine were administered orally for up to 96 weeks. Virologic and serologic responses were measured throughout the study. RESULTS: A significantly higher proportion of patients in the entecavir group achieved hepatitis B virus DNA < 60 IU/mL at Weeks 48 (100% [38/38] vs 62.8% [22/35]; P < 0.001) and 96 (97.4% [37/38] vs 57.1% [20/35]; P<0.001). A greater number of patients had virologic breakthrough (Week 96 cumulative incidence 42.9% vs 2.6%; P<0.001) and genotypic lamivudine resistance (28.6% [10/35] vs 0% [0/38]; P<0.001) in the lamivudine group. No serious adverse events or laboratory abnormalities were reported. CONCLUSIONS: Even after achieving virological suppression on lamivudine therapy, the risk of emergent lamivudine resistance increases over time. Switching to entecavir resulted in a maintained virologic response and superior serologic responses versus continued lamivudine therapy. This study supports a rationale for switching to entecavir in chronic hepatitis B patients with virological suppression on lamivudine.


Assuntos
Antivirais/administração & dosagem , Substituição de Medicamentos , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Lamivudina/administração & dosagem , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Guanina/administração & dosagem , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/diagnóstico , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
J Korean Med Sci ; 31(3): 403-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26955241

RESUMO

Multiple therapeutic modalities are available for hepatocellular carcinoma (HCC) treatment. We aimed to evaluate the trends for HCC treatment in Korea. Recent trends and patterns in treatment modalities were assessed in HCC patients who first registered for the Health Insurance Review Assessment Service between 2008 and 2012. From 2009 to 2012, 57,690 patients were diagnosed with HCC. Transcatheter arterial chemoembolization (TACE) was the most common treatment modality for initial treatment. Curative treatment modalities like hepatic resection, liver transplantation, and local ablation therapy increased gradually. The 3 most common treatment modalities (hepatic resection, local ablation therapy, TACE) used after initial treatment in 2009 were studied. Following initial hepatic resection, 44.5% of patients required re-treatment. TACE was the most common modality (in 48.3% of cases), while 15.0% of patients received local ablation therapy. After local ablation therapy, 55.4% of patients were re-treated, wherein 45.0% of patients received TACE and 31.5% received local ablation therapy. Following initial TACE, 73.9% patients were re-treated, most commonly with TACE (57.7%) followed by local ablation therapy (12.8%). While there were no significant differences between the initial and re-treatment modalities, various multiple treatments followed the initial treatment. The treatment modalities were interchangeable.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Idoso , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica , Terapia Combinada/tendências , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Revisão da Utilização de Seguros , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Prevalência , Inibidores de Proteínas Quinases/administração & dosagem , República da Coreia/epidemiologia , Sorafenibe
12.
J Korean Med Sci ; 31(10): 1604-10, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27550489

RESUMO

Analgesics, known to be hepatotoxic drugs, are frequently prescribed to patients with liver cirrhosis who are prone to drug-induced liver injury. No guidelines are available regarding the prescription of analgesics in these patients. Therefore, we aimed to evaluate the prescription pattern of most frequently used analgesics in patients with cirrhosis. We assessed the prescription pattern of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) in patients with liver cirrhosis registered in Health Insurance Review Assessment Service database between January 1, 2012 and December 31, 2012. A total of 125,505 patients with liver cirrhosis were registered from January 1, 2012 to December 31, 2012. Of that group, 50,798 (40.5%) patients claimed reimbursement for at least one prescription for acetaminophen or NSAIDs during the one year follow-up period. Overall, NSAIDs (82.7%) were more prescribed than acetaminophen (64.5%). NSAIDs were more prescribed than acetaminophen even in decompensated cirrhosis compared with compensated cirrhosis (71.5% vs. 68.8%, P value < 0.001). There was a marked difference in prescription preference between acetaminophen and NSAIDs among physicians. Internists more frequently prescribed acetaminophen than NSAIDs compared to other physicians (50.9% vs. 76.2%, P < 0.001). Gastroenterologists more frequently prescribed acetaminophen over NSAIDs compared to other internists (80.9% vs. 51.2%, P < 0.001). Analgesics were prescribed in 40.5% of patients with cirrhosis. NSAIDs were more frequently prescribed although they should be avoided. The prescription pattern of analgesics were different significantly among physicians in patients with liver cirrhosis. The harmful effects of NSAIDs in patients with cirrhosis should be reminded to all physicians prescribing analgesics.


Assuntos
Acetaminofen/uso terapêutico , Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Cirrose Hepática/diagnóstico , Acetaminofen/efeitos adversos , Idoso , Analgésicos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Bases de Dados Factuais , Feminino , Hepatite Viral Humana/complicações , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Sistema de Registros
13.
Cancers (Basel) ; 16(4)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38398229

RESUMO

Real-world data regarding treatment with atezolizumab plus bevacizumab in high-risk patients with advanced HCC are lacking. In this multicenter retrospective cohort study, a total of 215 patients with advanced HCC received atezolizumab plus bevacizumab treatment at four tertiary hospitals. High-risk patients were those with grade Vp4 portal vein thrombus, bile duct invasion, or more than 50% liver infiltration. In total, 98 (45.6%) were the high-risk population, 186 (86.5%) were considered to be Child-Pugh class A, and 128 (59.5%) had previously received neoadjuvant or concomitant radiation treatment. Median overall survival (OS) was 11.25 months (95% CI, 9.50-13.10), and the median progression-free survival (PFS) was 8.00 months (95% CI, 6.82-9.18). In the high-risk population, the median OS was 10 months (95% CI, 8.19-11.82) and the median PFS was 6.50 months (95% CI, 3.93-9.08). In the high-risk population, multivariate analysis indicated that radiation therapy and lower ALBI grade were associated with better OS and PFS. A total of 177 (82.3%) patients experienced adverse events of any grade, the most common being proteinuria (23.7%). Atezolizumab plus bevacizumab treatment showed consistent efficacy and tolerability in both the total and high-risk population. Radiation therapy combined with atezolizumab plus bevacizumab treatment might be helpful to improve PFS and OS in high-risk populations.

14.
Eur Radiol ; 23(5): 1288-96, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23223836

RESUMO

OBJECTIVES: To investigate the value of DWI for differentiating malignant from benign strictures in the periampullary region. METHODS: We retrospectively analysed data from 78 patients who had undergone magnetic resonance cholangiopanreatography (MRCP) and diffusion-weighted imaging (DWI), in whom biliary strictures in the periampullary region were suspected. Twenty-two malignant and 56 benign lesions were included. One radiologist compared the signal intensity of malignant and benign periampullary lesions on DWI using b = 500 and 800 s/mm(2). The signal intensity of bile was also compared, and an optimal b value was determined for periampullary lesions. Two other radiologists reviewed MRCP alone and combined DWI and MRCP for the possibility of malignant periampullary lesions. Diagnostic accuracy was calculated for each reviewer by receiver operating characteristic (ROC) curve analysis. RESULTS: Malignant periampullary lesions more frequently appeared hyperintense than benign lesions on DWI using the two b values (P < 0.001). Bile more frequently appeared hyperintense on DWI using b = 500 s/mm(2) (87.2 %) than b = 800 s/mm(2) (24.4 %). Therefore, b = 800 s/mm(2) was determined as the preferred sequence. Diagnostic accuracy for malignant periampullary lesions improved for both reviewers after adding DWI; from 0.714 to 0.924 (P = 0.006, for reviewer 1) and from 0.714 to 0.919 (P = 0.007, reviewer 2). CONCLUSIONS: Combined DWI with MRCP can improve the diagnostic accuracy for differentiating malignant from benign strictures in the periampullary region. KEY POINTS: • Diffusion-weighted magnetic resonance imaging provides yet more information about hepatobiliary structures. • Diffusion-weighted imaging (DWI) has now been applied to the biliary tree. • Most periampullary carcinomas appear hyperintense on high b value DWI. • DWI can help differentiate between malignant and benign periampullary lesions.


Assuntos
Ampola Hepatopancreática/patologia , Colangiopancreatografia por Ressonância Magnética/métodos , Neoplasias do Ducto Colédoco/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
15.
Pharmaceutics ; 15(2)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36839825

RESUMO

Immunotherapy is crucial in fighting cancer and achieving successful remission. Many novel strategies have recently developed, but there are still some obstacles to overcome before we can effectively attack the cancer cells and decimate the cancer environment by inducing a cascade of immune responses. To successfully demonstrate antitumor activity, immune cells must be delivered to cancer cells and exposed to the immune system. Such cutting-edge technology necessitates meticulously designed delivery methods with no loss or superior homing onto cancer environments, as well as high therapeutic efficacy and fewer adverse events. In this paper, we discuss recent advances in cancer immunotherapy delivery techniques, as well as their future prospects.

16.
Scand J Gastroenterol ; 47(7): 809-19, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22563643

RESUMO

OBJECTIVE: Sorafenib has been shown to improve survival of patients with advanced hepatocellular carcinoma (HCC). However, its tolerance in clinical practice has not been well evaluated, and whether sorafenib should be continued in cases of tumor progression or intolerance has not been established. The authors retrospectively assessed sorafenib tolerability, and evaluated the clinical course in patients who showed progression during sorafenib treatment. MATERIAL AND METHODS: Between March 2008 and July 2010, 80 patients with advanced HCC were treated with sorafenib. RESULTS: With a median of 78.5 days of treatment, 15% discontinued sorafenib due to adverse events. The duration was significantly longer in patients with Child-Pugh class A liver function (233 ± 240 days) than in those with Child-Pugh class B (100 ± 136 days; p = 0.006). The overall progression rate was 53% (43/80), with a median time to progression of 105 days (95% confidence interval, 59-150 days). After progression, 14 patients received conservative care only (group 1), 14 continued sorafenib monotherapy (group 2), 6 changed to treatment without sorafenib (group 3) and 9 underwent additional treatment with concomitant sorafenib (group 4). Survival after progression was significantly better in groups 2, 3 and 4 than in group 1 (p = 0.001). CONCLUSIONS: Sorafenib was tolerable for most patients in clinical practice and may be continued in patients who show progression during sorafenib therapy. However, it was less well tolerated in patients with Child-Pugh class B liver function and should be used with caution in these patients.


Assuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Piridinas/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Benzenossulfonatos/efeitos adversos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/fisiopatologia , Diarreia/induzido quimicamente , Progressão da Doença , Fadiga/induzido quimicamente , Feminino , Síndrome Mão-Pé/etiologia , Humanos , Estimativa de Kaplan-Meier , Falência Hepática/induzido quimicamente , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Niacinamida/análogos & derivados , Compostos de Fenilureia , Modelos de Riscos Proporcionais , Piridinas/efeitos adversos , Estudos Retrospectivos , Sorafenibe , Fatores de Tempo
17.
BMC Gastroenterol ; 12: 169, 2012 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-23185997

RESUMO

BACKGROUND: Gastric intestinal metaplasia (IM) usually appears in flat mucosa and shows few morphologic changes, making diagnosis using conventional endoscopy unreliable. Magnifying narrow-band imaging (NBI) endoscopy enables evaluation of detailed morphological features that correspond with the underlying histology. The aim of this study was to investigate and clarify the diagnostic efficacy of magnifying NBI endoscopic findings for the prediction and diagnosis of IM. METHODS: Forty-seven patients were prospectively enrolled, and magnifying NBI examinations were performed in the lesser curvature of the midbody and the greater curvature of the upper body. The marginal turbid band (MTB) was defined as an enclosing white turbid band on the epithelial surface/gyri; light blue crest (LBC), as a fine, blue-white line on the crest of the epithelial surface/gyri. Immediately after observation under magnifying endoscopy, biopsy specimens were obtained from the evaluated areas. RESULTS: The degree of IM significantly increased with increasing MTB/LBC positivity (MTB(-)/LBC(-), 0.00 ± 0.00; MTB(+)/LBC(-), 0.44 ± 0.51; MTB(+)/LBC(+), 0.94 ± 0.24; p < 0.001). Moderate-to-severe IM was more common in MTB(+)/LBC(+) areas than in MTB(+)/LBC(-) areas (p < 0.001). For the diagnosis of IM, MTB had a sensitivity, specificity, and accuracy of 100%, 66.0%, and 81.7%, respectively, and the corresponding values for LBC were 72.1%, 96.0%, and 84.9%. CONCLUSION: MTB and LBC observed in the gastric mucosa with magnifying NBI endoscopy are highly accurate indicators of the presence of IM. MTB likely represents a sign of early gastric IM, while LBC appears with progression to severe IM.


Assuntos
Mucosa Gástrica/patologia , Gastroscopia , Aumento da Imagem , Mucosa Intestinal/patologia , Luz , Adulto , Idoso , Feminino , Humanos , Masculino , Metaplasia , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
18.
Mol Ther ; 19(6): 1170-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21427706

RESUMO

JX-594 is a targeted and granulocyte-macrophage colony stimulating factor (GM-CSF) expressing oncolytic poxvirus designed to selectively replicate in and destroy cancer cells through viral oncolysis and tumor-specific immunity. In a phase 1 trial, JX-594 injection into hepatocellular carcinoma (HCC) was well-tolerated and associated with viral replication, decreased tumor perfusion, and tumor necrosis. We hypothesized that JX-594 and sorafenib, a small molecule inhibitor of B-raf and vascular endothelial growth factor receptor (VEGFR) approved for HCC, would have clinical benefit in combination given their demonstrated efficacy in HCC patients and their complementary mechanisms-of-action. HCC cell lines were uniformly sensitive to JX-594. Anti-raf kinase effects of concurrent sorafenib inhibited JX-594 replication in vitro, whereas sequential therapy was superior to either agent alone in murine tumor models. We therefore explored pilot safety and efficacy of JX-594 followed by sorafenib in three HCC patients. In all three patients, sequential treatment was (i) well-tolerated, (ii) associated with significantly decreased tumor perfusion, and (iii) associated with objective tumor responses (Choi criteria; up to 100% necrosis). HCC historical control patients on sorafenib alone at the same institutions had no objective tumor responses (0 of 15). Treatment of HCC with JX-594 followed by sorafenib has antitumoral activity, and JX-594 may sensitize tumors to subsequent therapy with VEGF/VEGFR inhibitors.


Assuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Piridinas/uso terapêutico , Vaccinia virus/fisiologia , Animais , Linhagem Celular Tumoral , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Melanoma/tratamento farmacológico , Melanoma/terapia , Camundongos , Camundongos SCID , Niacinamida/análogos & derivados , Terapia Viral Oncolítica/métodos , Compostos de Fenilureia , Sorafenibe , Vaccinia virus/genética , Ensaios Antitumorais Modelo de Xenoenxerto
19.
J Yeungnam Med Sci ; 39(3): 256-261, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34411476

RESUMO

Sarcoidosis often involves the liver. However, primary hepatic sarcoidosis confined to the liver without evidence of systemic involvement is rare. We report the case of a 37-year-old man with hepatic sarcoidosis who initially presented with elevated liver enzymes and suspicious cirrhotic nodules on computed tomography. The patient had cirrhosis but did not have portal hypertension. Based on the initial histopathologic finding of chronic granulomatous inflammation and the common clinical characteristics of sarcoidosis, he was initially diagnosed with primary biliary cholangitis, and his daily dosage of ursodeoxycholic acid was increased to 900 mg. After 14 months of treatment, his total serum bilirubin concentration was 10.9 mg/dL (upper normal limit, 1.2 mg/dL). Additionally, a transjugular liver biopsy revealed multiple noncaseating granulomas. He was diagnosed with primary hepatic sarcoidosis involving the lungs, heart, spleen, kidneys, and skin. Treatment with methylprednisolone was initiated. Two weeks later, he was started on azathioprine, and the dose of steroid was simultaneously reduced. These findings indicate the importance of including hepatic sarcoidosis as a possible diagnosis in patients with elevated liver enzymes or cryptogenic cirrhosis.

20.
J Yeungnam Med Sci ; 39(1): 18-23, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34247458

RESUMO

BACKGRUOUND: This study was performed to evaluate periprocedural factors, complications, and repuncture rate of the newly developed puncture needle and compare it with the routinely used puncture needle for ultrasound (US)-guided paracentesis. METHODS: We retrospectively identified 137 patients who underwent US-guided paracentesis between July 2018 and March 2019. Among them, 82 patients underwent US-guided paracentesis with a newly developed puncture needle. The other 55 patients underwent US-guided paracentesis with a routinely used puncture needle. The periprocedural factors, complications, and repuncture rate were compared between the two groups using the Mann-Whitney U test and Fisher exact test. The repuncture-associated factors were assessed using logistic regression analysis. RESULTS: There were no major or minor complications in either group. The rate of repuncture was significantly lower in the group using the newly developed puncture needle compared with the group using the routinely used puncture needle (p=0.01). The duration of the procedure was significantly shorter with the newly developed puncture needle compared with the routinely used puncture needle (p=0.01). In univariate analysis, the thickness of the abdominal wall (p=0.04) and the use of the newly developed puncture needle (p=0.01) were significantly associated with the rate of repuncture. In multivariate analysis, only the use of the newly developed puncture needle was significantly associated with the rate of repuncture. CONCLUSION: Using this novel puncture needle with a hard plastic sheath and plastic wings, the rate of repuncture and the duration of the procedure were decreased without complications of US-guided paracentesis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA