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OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION: Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pulmonares , Neoplasias Nasofaríngeas , Adolescente , Anticuerpos Monoclonales Humanizados , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Cisplatino/uso terapéutico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Nasofaríngeas/inducido químicamente , Neoplasias Nasofaríngeas/tratamiento farmacológicoRESUMEN
There are direct and indirect interactions between gut microbiota and host immune response, which can have a multifaceted impact on host health. Dysbiosis caused by disturbances in the gut microbiota is associated with susceptibility to many diseases, especially immune-related diseases. Based on the research results in recent years, this paper introduced the mechanism of the interaction between gut microbiota and host immunity, and expounded the role of gut microbiota in the occurrence and development of immune-related diseases, including intestinal system diseases such as inflammatory bowel disease and other systemic diseases such as rheumatoid arthritis, and summarized disease treatment strategies targeting gut microbiota. A better understanding of the research progress of gut microbiota and immune-related diseases will help us in the prevention and management of such diseases, and broaden our path to discover disease intervention targets.
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Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Microbioma Gastrointestinal/fisiología , Humanos , IntestinosRESUMEN
Objective: To examine the clinical characteristics, the potential relative factors for postoperative abdominal septic complications, and prognosis factors of surgical recurrence of Crohn disease (CD) patients after the first surgery. Methods: All the CD patients from Department of General Surgery, Jinling Hospital, Medical School of Nanjing University who had undergone at least one abdominal surgery from January 2007 to December 2017 were included for retrospective analysis. Hospital records were reviewed for information on clinical characteristics. Relative factors of postoperative abdominal septic complications were accessed by Logistic regression models, and prognosis factors of surgical recurrence were accessed by Cox proportional hazards regression models. Results: There were 1 048 patients included (733 males and 315 females), accounting for 1 513 operations. The age was 31(17) years and the length of resected small bowel was 30.0(40.0) cm at the first resection, 20.0(35.0) cm at the second resection, and 20.0(23.5) cm at the third resection. The length of resected small bowel was 25.0(40.0) cm at any resection. At the first abdominal surgery, 70.99%(744/1 048) patients were aged between 17 and 40 years, 66.98%(702/1 048) patients had ileocolonic disease, and 60.40%(633/1 048) patients had penetrating behavior. Penetrating behavior (OR=8.594, 95%CI: 3.397 to 21.740, P<0.01) and current smoking status (OR=2.671, 95%CI: 1.044 to 6.832, P=0.040) were significantly associated with an increased risk of postoperative septic complications, whereas staged operation (OR=0.360, 95%CI: 0.184 to 0.707, P=0.003) was associated with a decreased risk. Male gender (HR=1.500, 95%CI: 1.128 to 1.995, P=0.005), upper gastrointestinal disease (HR=1.526, 95%CI: 1.033 to 2.255, P=0.034), penetrating behavior (HR=1.506, 95%CI: 1.132 to 2.003, P=0.005) and emergency surgery (HR=1.812, 95%CI: 1.375 to 2.387, P<0.01) were significantly associated with an increased risk of postoperative surgical recurrence, whereas staged operation (HR=0.361, 95%CI: 0.227 to 0.574, P<0.01) was significantly associated with a decreased risk. Conclusions: In this cohort of CD patients receiving abdominal surgery from an inflammatory bowel disease center, the median age was 31 years and the median length of resected small bowel was 30 cm, at first resection. Patients who have risk factors of adverse postoperative outcome may be benefited from staged surgical approach.
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Enfermedad de Crohn , Procedimientos Quirúrgicos del Sistema Digestivo , Intestino Delgado/cirugía , Adolescente , Adulto , Anastomosis Quirúrgica , Enfermedad de Crohn/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Femenino , Humanos , Infecciones/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: To analyze the value of postoperative C-reactive protein (CRP) in predictive diagnosis of postoperative intra-abdominal septic complications (IASC) for patients with Crohn disease (CD). METHODS: Clinical data of patients with CD received intestinal resection and anastomosis surgery at Research Institute of General Surgery, Jinling Hospital from January 2011 to January 2015 were analyzed. Patients were divided into two groups by whether suffer from IASC 1 month after surgery, including IASC group and no-IASC group. Propensity score matching method was used to match the general clinical data. A total of 54 patients were analyzed, including IASC 17 cases, no-IASC 37 cases. Postoperative CRP at 1-day and 3-day were compared between the two groups using t test. Receiver operator characteristic (ROC) cure was used to analyze the value of postoperative CRP in predictive diagnosis of IASC. RESULTS: IASC group had higher levels of CRP at 1-day ((78±13) mg/L vs. (54±19) mg/L, t=4.633, P=0.000) and 3-day ((103±19) mg/L vs. (69±21) mg/L, t=5.859, P=0.000) after surgery than no-IASC group. ROC analysis showed that the CRP 3-day after surgery cut-off point value of 81.45 mg/L, as used for the predictive diagnosis of IASC, provided a sensitivity of 94.1%, a specificity of 82.9%, an area under the curve of 0.90, better than CRP 1-day after surgery. CONCLUSION: Postoperative CRP can be used as a predictive diagnosis of IASC for CD patients received intestinal resection and anastomosis surgery.
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Anastomosis Quirúrgica , Proteína C-Reactiva/análisis , Enfermedad de Crohn/cirugía , Complicaciones Posoperatorias/sangre , Sepsis/sangre , Sepsis/diagnóstico , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Enfermedad de Crohn/sangre , Femenino , Humanos , Masculino , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Curva ROC , Sensibilidad y Especificidad , Sepsis/microbiologíaRESUMEN
No standard treatment is currently available for gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC). Therefore, we conducted this study to evaluate the effect of the combination of irinotecan and cisplatin in the treatment of GEP-NECs. Clinical data of 16 locally advanced or metastatic GEP-NEC patients treated with irinotecan plus cisplatin regimen in our center from September 2009 to August 2011 were reviewed. The regimen included 2-week cycles of 180 mg/m(2) irinotecan and 50 mg/m(2) cisplatin on day 1. Median age was 57 years. The overall response rate was 57.1%, with a disease control rate of 78.6%. One patient achieved pathologic complete response and underwent esophagectomy after chemotherapy. Two patients who had gotten progressive disease were given sequential octreotide long-acting release (LAR) treatment and got disease progression again within 1 month. Six patients who achieved disease control received octreotide LAR as maintenance treatment. The total number of cycles of octreotide was 41, with a median of 4.5 (3-20 cycles). The progression-free survival was 5.5 months, with overall survival of 10.6 months. Grades 3-4 hematological adverse events (AEs) occurred in 10 patients (62.5%) and 3 patients (18.7%) suffered grades 3-4 non-hematological AEs; no patient died of AEs. The irinotecan plus cisplatin chemotherapy is moderately effective and tolerable well tolerated in advanced or metastatic GEP-NEC patients; octreotide LAR may be a good maintenance treatment and should be considered as a treatment option for these patients in the future.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Neuroendocrino/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Carcinoma Neuroendocrino/mortalidad , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Irinotecán , Masculino , Persona de Mediana EdadRESUMEN
Ubiquitin (Ub) is regarded as a stress protein involved in many stress responses. In this paper, sense and antisense transgenic tobacco plants, as well as the wild type and vector control, were used to study the role of Ub in salt tolerance of plants. In sense Ta-Ub2 transgenic tobacco plants, there was higher expression of Ub protein conjugates than in the wild type and vector control, but the reverse trend was observed in antisense Nt-Ub1 transgenic plants. The germination rate of tobacco seed, growth status and photosynthesis of the tobacco plants suggested that over-expressing Ub promoted the growth of transgenic tobacco plants and enhanced their salt tolerance, but the opposite effect was seen in plants with repressed Ub expression. Changes in antioxidant capacity may be one of the mechanisms underlying Ub-regulated salt tolerance. Furthermore, improved tolerance to a combination of stresses was also observed in the sense transgenic tobacco plants. These findings imply that Ub is involved in the tolerance of plants to abiotic stress.
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Nicotiana/fisiología , Tolerancia a la Sal/fisiología , Estrés Fisiológico/fisiología , Ubiquitinas/genética , Antioxidantes/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Genotipo , Germinación/efectos de los fármacos , Estrés Oxidativo , Fenotipo , Fotosíntesis/efectos de los fármacos , Complejo de Proteína del Fotosistema II/efectos de los fármacos , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/fisiología , Transpiración de Plantas/efectos de los fármacos , Plantas Modificadas Genéticamente , Especies Reactivas de Oxígeno/metabolismo , Plantones/efectos de los fármacos , Plantones/fisiología , Semillas/efectos de los fármacos , Semillas/fisiología , Cloruro de Sodio/farmacología , Nicotiana/efectos de los fármacos , Nicotiana/genética , Ubiquitinas/metabolismoRESUMEN
AIMS: This study aims to determine whether adjuvant treatment with imatinib improves recurrence-free survival (RFS) in Chinese patients undergoing complete resection of localized primary gastrointestinal stromal tumor (GIST) compared with those not receiving adjuvant therapy. We also sought a correlation between c-KIT mutations and RFS. METHODS: Patients who had undergone complete tumor resection with intermediate or high risk of recurrence were enrolled in a single-center, non-randomized, prospective study. Patients either received adjuvant imatinib therapy (400 mg once-daily) for 3 years or did not. Mutation analyses of c-KIT were performed on available archival tumor samples. RESULTS: 105 patients were enrolled: 56 in the treatment group and 49 in the control group. Median follow-up was 45(43.1-46.9) months. RFS at 1, 2 and 3 years were higher in the treatment group than in the control group (100% vs. 90% at 1 year; 96% vs. 57% at 2 years; 89% versus 48% at 3 years, P < 0.001, HR = 0.188). Subgroup analyses showed that adjuvant therapy significantly decreased the risk of recurrence in patients whether at high risk or at intermediate risk compared with control patients (3-year RFS: 95% vs. 72%, in intermediate risk; 85% versus 31% in high risk; P < 0.001). In addition, imatinib adjuvant treatment decreased the risk of death (P = 0.025, [corrected] HR = 0.254). CONCLUSIONS: Adjuvant imatinib can improve 1-, 2- and 3-year RFS rates in patients at intermediate or high risk of recurrence after complete tumor resection. CLINICAL TRIALS REGISTRATION NUMBER: ChiCTR-TCC-00000582.
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Antineoplásicos/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/mortalidad , Mutación , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-kit/genética , Pirimidinas/uso terapéutico , Antineoplásicos/administración & dosificación , Pueblo Asiatico , Benzamidas , Quimioterapia Adyuvante , China , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Gastrectomía , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Mesilato de Imatinib , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Piperazinas/administración & dosificación , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirimidinas/administración & dosificación , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
Hexagonal single-crystal AlN nanowires with straight or zigzag morphologies were successfully synthesized by the reaction of aluminum alloy in an ammonia/nitrogen atmosphere at 1100 degrees C. It is found that the crystal tropism of the nanowires is along [0001], whereas the growth directions of the zigzag nanowires shift between [2111] and [2111].