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2.
Gan To Kagaku Ryoho ; 46(9): 1367-1371, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31530772

RESUMO

Recent advances in cancer immunotherapies, such as immune checkpoint inhibitors(ICIs), have shown some durable clinical responses in patients with various types of advanced cancers. The development of the next-generation sequencing technologies can result in a comprehensive characterization of the human cancer genomes. Personalized immunotherapy and precision cancer medicine might enable the next generation of rational cancer immunotherapy. Conventional cancer vaccines are designed to target tumor-associated antigens(TAAs), which are overexpressed in cancers. However, since TAAs are also expressed in normal tissues, cancer vaccine against TAAs can potentially initiate central and peripheral tolerance responses, which results in low vaccination efficiency. Cancer neoantigens derived from somatic mutations in tumor tissue represent highly immunogenic and can escape from central thymic tolerance. They are suggested to provide tumor specific targets for personalized cancer vaccines. Therefore, neoantigen-based cancer vaccine, which can induce tumor-specific cytotoxic T lymphocytes( CTLs), should be developed. The efficacy of current immunotherapies also remains limited due to the immunosuppressive tumor microenvironment, which leads to CTLs exhaustion or anergy and the escape of tumor cells from immune attack. The combination of neoantigen-based cancer vaccine and ICIs should be a potential therapeutic approach. In this paper, we provide a brief overview of the recent advances in the development of neoantigen-based cancer vaccines.


Assuntos
Vacinas Anticâncer , Neoplasias , Antígenos de Neoplasias , Humanos , Imunoterapia , Medicina de Precisão , Microambiente Tumoral
3.
Br J Cancer ; 121(8): 659-665, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31488881

RESUMO

BACKGROUND: CD3 + and CD8 + T-cell infiltration were reported as positive predictive markers of survival in colorectal cancer (CRC) patients. Here, we demonstrate the prognostic significance of CD4 + and FOXP3 + T-cell densities in CRC. METHODS: We quantified the intratumoural densities of CD3 + , CD8 + , CD4 + and FOXP3 + T cells by immunohistochemistry and digital pathology in 342 CRC patients who underwent curative resection. Microsatellite instability was also assessed in 322 specimens. Patient demographics, clinicopathological features and survival rates were analysed. RESULTS: High CD3 + , CD4 + and FOXP3 + T-cell densities were associated with improved relapse-free survival (RFS); high CD8 + , CD4 + and FOXP3 + T-cell densities were associated with improved disease-specific survival (DSS). Patients with low CD4 + and low FOXP3 + T-cell densities exhibited extremely poor prognoses. T stage, vascular/lymphatic invasion and CD4 + T-cell density were independent prognostic indicators for DSS. The distributions of CD4 + and FOXP3 + T-cell densities were not significantly different between the high microsatellite instability group and other groups, in contrast to those of CD3 + and CD8 + T-cell densities. CONCLUSIONS: Intratumoural CD4 + T-cell density and combined CD4 + and FOXP3 + T-cell densities were stronger prognostic indicators than other clinicopathological features. These results may facilitate the establishment of novel prognostic factors and therapeutic strategies for CRC.

4.
J Immunother ; 42(7): 244-250, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31398179

RESUMO

We previously found that heat-shock protein 70 (HSP70) is expressed on hepatocellular carcinoma cells and developed an HSP70 mRNA-transfected dendritic cell therapy for treating unresectable or recurrent hepatocellular carcinoma. The phase I trial was completed successfully. The purpose of this study is to identify a promiscuous epitope peptide derived from HSP70 for the purpose of developing a novel cancer peptide vaccine. Using a computational algorithm to analyze the specificity of previously reported major histocompatibility complex class I-binding peptides, we selected candidates that bound to >2 of the 3 HLA types. Twenty-nine HSP70-derived peptides (9-mers) that bound to HLA-class I was selected. The peptides were prioritized based on the results of peptide binding experiments. Using dendritic cells stimulated with the candidate peptide described previously as stimulators and CD8 T cells as effectors, an ELISPOT assay was performed. Cytotoxicity of CD8 lymphocytes stimulated with the candidate peptides toward HSP70-expressing cancer cells was analyzed using an xCELLigence System. Peptides were administered to HLA-A 24 transgenic mice as vaccines, and peptide-specific T-cell induction was measured in vivo. We identified a multi-HLA-class I-binding epitope peptide that bound to HLA-A*02:01, *02:06, and *24:02 in vitro using an interferon-γ ELISPOT immune response induction assay. Cytotoxicity was confirmed in vitro, and safety and immune response induction were confirmed in vivo using HLA-A 24 transgenic mice. Our study demonstrated that the promiscuous HSP70-derived peptide is applicable to cancer immunotherapy in patients with HLA-A*24:02-positive, *02:01-positive, and *02:06-positive HSP70-expressing cancers.

5.
Gan To Kagaku Ryoho ; 46(4): 760-762, 2019 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-31164527

RESUMO

We have performed a combination therapy of hepatic arterial infusion chemotherapy(HAIC), radiation therapy(RT), and surgical resection for the treatment of hepatocellular carcinoma(HCC)with portal vein tumor thrombosis(PVTT)since 2013. We retrospectively analyzed 36 patients with HCC with PVTT who underwent hepatectomy between 1995 and 2016 to evaluate the clinical outcomes. Ten patients received preoperative HAIC, 7 underwent RT, and 14 received postoperative HAIC. The median survival time(MST)was 19.3 months, and the MST was significantly longer in the patients who underwent curative resection than those in patients who did not. In the non-curative resection group, postoperative HAIC prolonged the survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Veia Porta , Estudos Retrospectivos , Trombose , Resultado do Tratamento
6.
Gan To Kagaku Ryoho ; 46(2): 324-326, 2019 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-30914548

RESUMO

Case 1: A 64-year-old man with a chiefcomplaint ofbloody stools was seen in our hospital. He underwent an extended right lobe resection for hilar cholangiocarcinoma 3 years ago and was in the middle of chemotherapy for multiple metastases. Case 2: A 69-year-old man with a chiefcomplaint ofbloody emesis and stools was seen. He underwent left hepatic trisegmentectomy for hilar cholangiocarcinoma and ligation of the right portal vein for postoperative portal venous thrombus 6 months ago. After careful examination, the patients in both cases were diagnosed with bleeding of the jejunal varices formed at the site ofhepaticojejunostomy. The patient in Case 1 underwent percutaneous transhepatic obliteration ofvarices and the patient in Case 2 underwent transileocolic vein obliteration ofvarices. After hepatobiliary pancreatic surgery with biliary tract reconstruction, we should be aware of ectopic varices during differential diagnosis of gastrointestinal bleeding.


Assuntos
Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma , Tumor de Klatskin , Varizes , Idoso , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/complicações , Colangiocarcinoma/cirurgia , Humanos , Tumor de Klatskin/complicações , Tumor de Klatskin/cirurgia , Masculino , Pessoa de Meia-Idade , Ruptura/etiologia , Varizes/patologia
7.
Gan To Kagaku Ryoho ; 46(3): 526-528, 2019 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-30914603

RESUMO

A 65-year-old woman with cecum cancer underwent laparoscopic right colectomy.After 3 years, she was diagnosed with a local recurrence with small bowel invasion and underwent tumor resection.One year later, she had a re-recurrent lesion involving her right iliac bone.After one year of chemotherapy, a PET-CT showed no other abdominal lesions suggestive of malignancy.She underwent resection of the re-recurrent tumor involving the right iliac bone and R0 resection was achieved. She was able to ambulate postoperatively and returned home.In selected cases, extended surgery including bone resection can be an option for the local recurrence of advanced colon cancer.


Assuntos
Neoplasias do Colo , Ílio , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Colectomia , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Ílio/patologia , Recidiva Local de Neoplasia
8.
Gan To Kagaku Ryoho ; 46(3): 543-545, 2019 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-30914608

RESUMO

A 77-year-old man underwent a follow-up examination after distal gastrectomy. Contrast-enhanced computed tomography revealed a tumor of the pancreatic body and tail that contacted the common hepatic artery/celiac artery. Subsequently, the tumor was diagnosed as a borderline resectable pancreatic cancer. After chemoradiation therapy, the tumor was considered resectable. Preoperative angiography with intraoperative contrast-enhanced ultrasonography and indocyanine green fluorescence imaging confirmed blood flow in the residual stomach. Postoperatively, ischemic necrosis of the residual stomach was not observed. After distal gastrectomy, distal pancreatectomy with en bloc celiac axis resection was performed to safely and curatively address the cancer of the pancreatic body and tail.


Assuntos
Artéria Celíaca , Gastrectomia , Pancreatectomia , Neoplasias Pancreáticas , Idoso , Quimiorradioterapia , Artéria Hepática , Humanos , Masculino , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia
9.
Exp Suppl ; 108: 235-268, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30536174

RESUMO

Many diseases of the gastrointestinal tract have been attributed to chronic inflammation, and a few have identified the role of inflammasomes in their pathogenesis. Inflammasomes are a group of protein complexes comprising of several intracellular proteins that link the sensing of microbial products and metabolic stress to the proteolytic activation of the proinflammatory cytokines. Recent studies have implicated activation of several families of NOD-like receptors (NLRs) which are major components of inflammasomes in the development and exacerbation of many diseases of human systems. In this chapter, we discuss the role of inflammasomes in some of the most prevalent diseases of the gastrointestinal tract and highlight potential targets for treatment.


Assuntos
Gastroenteropatias/imunologia , Inflamassomos , Humanos , Inflamação/imunologia , Proteínas NLR/metabolismo
10.
Nutrition ; 59: 96-102, 2018 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-30468936

RESUMO

OBJECTIVE: Malnutrition is common in patients with esophageal cancer, resulting in increased postoperative complications and mortality. Although preoperative immunonutrition can significantly reduce the incidence of postoperative infectious complications, its effect in patietns with esophageal cancer undergoing esophagectomy remains unclear. The aim of this study was to investigate the effects of perioperative immunonutritional support on the postoperative course and long-term survival of this group of patients. METHODS: This prospective, randomized study enrolled 40 patients with thoracic esophageal carcinoma undergoing esophagectomy. The patients were divided into two groups and received either immunomodulating enteral nutrition (IMPACT group; IG) or standard enteral nutrition (Ensure group; EG) continuously for 7 d before and 7 d after surgery. Nutritional status, such as rapid turnover protein, postoperative intensive care unit (ICU) length of stay (LOS), postoperative hospital LOS, morbidity, and mortality were investigated prospectively. RESULTS: There were no significant differences in patient demographic characteristics between the two groups. Levels of retinol-binding protein, as a rapid-turnover protein, were significantly higher on postoperative day (POD) -1, 7, and 14 in the IG compared with the EG group (P = 0.009, P = 0.004, and P = 0.024, respectively). The incidence of postoperative infectious complications and changes to therapeutic antibiotics were significantly lower in the IG group than in the EG group (P = 0.048 and P = 0.012, respectively). There was no significant difference in postoperative ICU or postoperative hospital LOS between the two groups. The 5-y progression-free survival rates in the IG and EG groups were 75% and 64%, respectively (P = 0.188), and the overall survival rates were 68% and 55%, respectively (P = 0.187). CONCLUSIONS: Perioperative immunonutrition may improve early postoperative nutritional status and reduce postoperative infectious complications in patients with esophageal cancer undergoing esophagectomy.

12.
Expert Rev Anticancer Ther ; 18(12): 1205-1217, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30295097

RESUMO

INTRODUCTION: Pancreatic cancer is a highly malignant disease with high treatment resistance. Many patients are diagnosed in a very advanced state, and few patients can be curatively resected. With FOLFIRINOX and nab-paclitaxel plus gemcitabine, the prognosis of advanced pancreatic cancer has improved, yet many patients cannot survive longer than a year. Therefore, new therapeutic approaches are needed. Cancer vaccine therapy is characterized by controlling cancer by a cancer-specific immune reaction with few adverse events. Thus, a cancer peptide vaccine is considered promising for pancreatic cancer patients, who are often in poor general condition at diagnosis. Areas covered: This article reviews available data from recent clinical trials of the novel cancer vaccine therapy in combination with traditional chemotherapy or radiotherapy for pancreatic cancer, and the prospect will be described. Expert commentary: In clinical trials of the novel cancer vaccine therapy in combination with traditional therapy, many studies have failed to outperform traditional therapy, although some effects were recognized in subgroups. What is necessary in the future for cancer vaccine therapy to improve the prognosis of pancreatic cancer is combination of immune-checkpoint blockade to release immune escape mechanism and combination with strong multi-drug combination chemotherapy.

13.
Oncol Rep ; 39(5): 2385-2392, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29498403

RESUMO

Cancer vaccines have been developed as a new therapeutic approach, however, their clinical benefit remains limited. We previously performed a phase II study for advanced colorectal cancer (CRC) using five human leukocyte antigen (HLA-A*24:02)-restricted peptides derived from kinase of the outer chloroplast membrane 1, translocase of outer mitochondrial membrane 34 (TOMM34), ring finger protein 43 (RNF43), vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2. In the present study the relationship between overall survival (OS) and several biomarkers, including cytotoxic T lymphocyte (CTL) and immunoglobulin G (IgG) responses to these five peptides, was investigated. In 89 advanced CRC patients treated with a combination therapy consisting of these five peptides and oxaliplatin-based chemotherapy, plasma was collected before and after 3 months of vaccine administration. IgGs reactive to each of the five peptides were assessed using the multiplex bead suspension Luminex system. Antigen-specific T-cell responses were estimated by enzyme-linked immunoSpot assay. Plasma levels of TOMM34 IgG (P<0.001), RNF43 IgG (P<0.001) and VEGFR2 IgG (P<0.001) were significantly increased after vaccination and stronger VEGFR2 IgG responses correlated significantly with OS in HLA-matched patients (P=0.034). CTL responses to VEGFR1 and VEGFR2 were also significantly increased in the HLA-matched group (P=0.049 and P<0.001, respectively). However, increased CTL response did not correlate with OS. Multivariate analysis indicated that IgG responses to VEGFR2 were the most significant predictor for OS in the HLA-A*24:02-matched group (P=0.04). Our findings indicated that VEGFR2 IgG responses may be an important immunological biomarker in the early course of treatment for CRC patients treated with therapeutic epitope peptides.


Assuntos
Vacinas Anticâncer/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Antígeno HLA-A24/imunologia , Imunoglobulina G/metabolismo , Idoso , Vacinas Anticâncer/imunologia , Neoplasias Colorretais/imunologia , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/imunologia , Método Duplo-Cego , Epitopos/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Transporte da Membrana Mitocondrial/química , Proteínas de Transporte da Membrana Mitocondrial/imunologia , Proteínas Oncogênicas/química , Proteínas Oncogênicas/imunologia , Análise de Sobrevida , Resultado do Tratamento , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/química , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/imunologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/química , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/imunologia
14.
Surg Endosc ; 32(4): 1945-1953, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29075967

RESUMO

BACKGROUND: In this study, cytokine levels, outcome, and survival rates after esophagectomy for esophageal cancer were retrospectively investigated in a propensity score-matched comparison of operative approaches between the thoracoscopic esophagectomy (TE) in the prone position and open esophagectomy (OE). PATIENTS AND METHODS: Between 2005 and 2014, TE was performed on a group of 85 patients, which was compared with a group of 104 OE cases. Eventually, 65 paired cases were matched using propensity score matching. RESULTS: Although the TE group underwent a significantly longer operation time than the OE group (P < 0.001), the TE group exhibited less blood loss (P < 0.001) and had a shorter postoperative hospital stay (P = 0.038) than the OE group. The serum interleukin-6 levels on ICU admission (P < 0.001) and on POD 1 (P < 0.001) were significantly lower in the TE group. The interleukin-10 levels on ICU admission (P < 0.001), POD 1 (P = 0.016), and POD 3 (P < 0.001) were also significantly lower in the TE group. Pulmonary complication was significantly lower in the TE group (P = 0.043). The 5-year PFS rates in the TE and OE groups were 70.6 and 58.7% (P = 0.328), respectively, and OS rates were 64.9 and 50.2% (P = 0.101), respectively. CONCLUSION: TE compared to OE is a less invasive procedure with lower surgical stress and less pulmonary complication for the treatment of esophageal squamous cell carcinoma.

15.
Ann Clin Biochem ; 55(1): 59-68, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28081635

RESUMO

Background As TWIST1 methylation is specific to colorectal neoplasia, detection of TWIST1 methylation from faeces samples might be useful for colorectal neoplasia screening. However, because the content of human DNA in faeces is very small, it is very difficult to detect TWIST1 methylation by conventional bisulphite-based methylation assays. Therefore, we developed a new methylation assay without bisulphite treatment, the combined restriction digital PCR assay, and evaluated its sensitivity and specificity in combination with and without the faecal immunochemical test for haemoglobin for colorectal neoplasia detection from faeces samples. Methods For the combined restriction digital PCR assay, DNA was treated with three methylation-sensitive restriction enzymes and an exonuclease, followed by measurement of TWIST1 methylation level by droplet digital PCR. Faecal DNA testing and faecal immunochemical test for haemoglobin were performed on 109 patients with colorectal neoplasia and 10 control individuals. Results Basic performance testing showed that the combined restriction digital PCR assay enabled detection of 0.14% of the TWIST1 methylation level for the lymphocyte DNA. The combined restriction digital PCR assay from faeces samples had a sensitivity of 22.2% (95% confidence interval, 2.8-60.0%) for non-advanced adenoma, 47.1% (95% confidence interval, 23.0-72.2%) for advanced adenoma, and 33.7% (95% confidence interval, 23.7-45.0%) for colorectal cancer, and a specificity of 100.0%. Combination of faecal immunochemical test for haemoglobin and faecal combined restriction digital PCR assay increased sensitivity to 82.4% (95% confidence interval, 56.6-96.2%) for the detection of advanced adenoma. Conclusions We developed the combined restriction digital PCR assay, a possible highly sensitive methylation assay. Combination of faecal combined restriction digital PCR assay with faecal immunochemical test for haemoglobin may provide an alternative screening strategy for colorectal neoplasia, especially for potentially precancerous lesions.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/diagnóstico , DNA/genética , Fezes , Hemoglobinas/metabolismo , Proteínas Nucleares/genética , Proteína 1 Relacionada a Twist/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Sensibilidade e Especificidade
16.
Cancer Sci ; 108(11): 2229-2238, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28859241

RESUMO

Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of the present study was to explore microRNAs (miRNAs) as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. First, we carried out microarray analysis of pretreatment cancer tissues in a phase I study, in which peptide vaccines alone were given. Candidate miRNAs were selected by comparison of the better prognosis group with the poorer prognosis group. Next, we conducted microarray analysis of cancer tissues in a phase II study, in which peptide vaccines combined with chemotherapy were given. Candidate miRNAs were further selected by a similar comparison of prognosis. Subsequently, we carried out reverse-transcription PCR analysis of phase II cases, separating cancer tissues into cancer cells and stromal tissue using laser capture microdissection. Treatment effect in relation to overall survival (OS) and miRNA expression was analyzed. Three miRNA predictors were negatively associated with OS: miR-125b-1 in cancer cells (P = 0.040), and miR-378a in both cancer cells (P = 0.009) and stromal cells (P < 0.001). Multivariate analysis showed that expression of miR-378a in stromal cells was the best among the three predictors (HR, 2.730; 95% CI, 1.027-7.585; P = 0.044). In conclusion, miR-125b-1 and miR-378a expression might be considered as novel biomarkers to predict the efficacy of vaccine treatment against colorectal cancer.


Assuntos
Vacinas Anticâncer/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Animais , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Feminino , Humanos , Microdissecção e Captura a Laser , Masculino , Camundongos , Análise em Microsséries , Prognóstico , Vacinas de Subunidades/administração & dosagem
17.
Oncol Lett ; 14(2): 1355-1362, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28789351

RESUMO

MicroRNAs (miRNAs/miRs) regulate the levels of transcripts and serve a critical function in the regulation of tumor microenvironments. Therefore, miRNA levels in cancer tissues are thought to be potential biomarkers for immunotherapy. From a phase I trial of a vaccine treatment using 5 human leukocyte antigen (HLA)-A*2402-restricted peptides (registration no. UMIN000004948), colorectal cancer (CRC) tissues were obtained from 8 patients and normal colorectal tissues from 5 patients via surgery. From a phase II trial using the same peptides (registration no. UMIN000001791), CRC tissues were obtained from 16 patients from the HLA-A*2402-matched group and 10 patients from the HLA-A*2402-unmatched group. These tissues were used for miRNA microarray analysis. As the first step, cancer tissues from the phase I study were used and 10 candidate miRNAs were selected by comparing the miRNA expression between two groups; one with improved prognosis and the other with poor prognosis. The miRNAs were subsequently validated using the cases enrolled in the phase II study. Significantly improved prognoses were identified in 16 patients in the HLA-A*2402-matched group with high expression of miR-196b-5p and low expression of miR-378a-3p and miR-486-5p. There was no difference in prognosis in the 10 patients in the HLA-A*2402-unmatched group. Therefore, high miR-196b expression and low miR-378a-3p and miR-486-5p expression were indicated as useful biomarkers for prediction of the efficacy of vaccine treatment for patients with metastatic CRC. In a planned phase III study, expression levels of these 3 miRNAs (miR-196b-5p, miR-378a-3p and miR-486-5p) may be useful biomarkers for assessing patients who are likely to have an improved outcome following vaccination.

18.
Pancreas ; 46(8): 994-1002, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28697053

RESUMO

OBJECTIVES: We previously described adoptive immunotherapy (AIT) with cytotoxic T lymphocytes (CTLs) stimulated by the mucin 1 (MUC1)-expressing human pancreatic cancer cell line YPK-1 (MUC1-CTLs) and demonstrated that MUC1-CTLs might prevent liver metastasis. In the present study, we combined gemcitabine (GEM) and AIT for the treatment of pancreatic cancer. METHODS: A total of 43 patients who underwent radical pancreatectomy received treatment with MUC1-CTLs and GEM. After surgery, MUC1-CTLs were induced and administered intravenously 3 times, and GEM administered according to the standard regimen for 6 months. The patients whose relative dose intensity of GEM was 50% or more and who received 2 or more MUC1-CTL treatments were used as the adequate treatment group (n = 21). RESULTS: In the adequate treatment group, disease-free survival was 15.8 months, and overall survival was 24.7 months. Liver metastasis was found only in 7 patients (33%), and local recurrence occurred in 4 patients (19%). The independent prognostic factor of long-term disease-free survival on multivariate analysis was the average number of CTLs administered (P = 0.0133). CONCLUSIONS: The combination therapy with AIT and GEM prevented liver metastasis and local recurrence. Moreover, the disease free-survival was improved in patients who received sufficient CTLs.


Assuntos
Desoxicitidina/análogos & derivados , Imunoterapia Adotiva/métodos , Neoplasias Hepáticas/prevenção & controle , Neoplasias Pancreáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Terapia Combinada , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Feminino , Humanos , Imunoterapia Adotiva/efeitos adversos , Estimativa de Kaplan-Meier , Leucopenia/etiologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Período Pós-Operatório
19.
Curr Opin Organ Transplant ; 22(5): 444-451, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28719390

RESUMO

PURPOSE OF REVIEW: Total pancreatectomy with islet autotransplantation (TPIAT) is a reliable therapy to retain endocrine function, to alleviate pain and improve quality of life in adult and pediatric patients suffering from refractory chronic pancreatitis and recurrent acute pancreatitis. Recently, an expansion of indications to include benign and malignant pancreatic disease has been suggested. Improved methods for evaluating the functional quality of islets and predicting transplant outcome have been discussed. Furthermore, this review will discuss the recent advances in the procedure, anti-inflammatory strategies and outcomes of TPIAT. RECENT FINDINGS: New assays to measure posttransplant islet damage and improved methods to assess islet quality by monitoring the oxygen consumption rate have shown great promise. Anti-inflammatory strategies such as an interleukin-1 receptor antagonist, α-1 antitrypsin, tumor necrosis factor α inhibitor and an inhibitor of CXCR1/2 have been widely investigated under clinical trials. SUMMARY: The primary objective of TPIAT, which is to relieve pain and reduce narcotic usage, has been shown to have long-term success. However, achieving long-term insulin independence is still a challenge that needs to be addressed. The mechanism that leads to chronic graft failure in TPIAT needs to be delineated.


Assuntos
Transplante das Ilhotas Pancreáticas/métodos , Pancreatectomia/métodos , Pancreatite/cirurgia , Qualidade de Vida/psicologia , Transplante Autólogo/métodos , Feminino , Humanos , Resultado do Tratamento
20.
Breast Cancer ; 24(6): 783-789, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28439763

RESUMO

BACKGROUND: Nanoparticle albumin-bound (nab)-paclitaxel is a solvent-free formulation of paclitaxel that is bound to albumin and has demonstrated improved progression free survival in previous studies of breast cancer. However, it is difficult to treat Japanese patients with metastatic or recurrent breast cancer with the recommended dose of 260 mg/m2 of (nab)-paclitaxel for more than six cycles due to the occurrence of adverse events. To evaluate the treatment continuity and safety of low-dose nab-paclitaxel, we conducted a phase II study of nab-paclitaxel in patients with metastatic or recurrent breast cancer who had received up to one prior chemotherapy. PATIENTS AND METHODS: Treatment included low doses of 180 mg/m2 nab-paclitaxel that were administered on day 1 of each 3-week cycle to 35 patients. The primary endpoint was the completion rate of six cycles of treatment. RESULTS: A total of 35 eligible patients were enrolled and received a median of eight (range 2-24) cycles of low-dose nab-paclitaxel therapy. The completion rate of six cycles of treatment was 66%. ORR and clinical benefit rate was 23 and 71%, respectively. Median PFS was 6.5 months and median OS was 44 months. Adverse events were relatively mild. Commonly observed grade 3/4 adverse events were neutropenia (46%), leukopenia (9%), and hypertension (3%). No grade 3-4 peripheral sensory neuropathy occurred. CONCLUSION: Treatment with a low dose of nab-paclitaxel once every 3 weeks was tolerable and of acceptable safety and might be beneficial for patients with metastatic or recurrent breast cancer.


Assuntos
Albuminas/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/uso terapêutico , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Incidência , Leucopenia/induzido quimicamente , Leucopenia/epidemiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Resultado do Tratamento
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