RESUMEN
PURPOSE: With the treatment of nasopharyngeal carcinoma (NPC) by PD-1/PD-L1 inhibitors used widely in clinic, it becomes very necessary to anticipate whether patients would benefit from it. We aimed to develop a nomogram to evaluate the efficacy of anti-PD-1/PD-L1 in NPC patients. METHODS: Totally 160 NPC patients were enrolled in the study. Patients were measured before the first PD-1/PD-L1 inhibitors treatment and after 8-12 weeks of immunotherapy by radiological examinations to estimate the effect. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to screen hematological markers and establish a predictive model. The nomogram was internally validated by bootstrap resampling and externally validated. Performance of the model was evaluated using concordance index, calibration curve, decision curve analysis and receiver operation characteristic curve. RESULTS: Patients involved were randomly split into training cohort ang validation cohort. Based on Lasso logistic regression, systemic immune-inflammation index (SII) and ALT to AST ratio (LSR) were selected to establish a predictive model. The C-index of training cohort and validating cohort was 0.745 and 0.760. The calibration curves and decision curves showed the precise predictive ability of this nomogram. The benefit of the model showed in decision curve was better than TNM stage. The area under the curve (AUC) value of training cohort and validation cohort was 0.745 and 0.878, respectively. CONCLUSION: The predictive model helped evaluating efficacy with high accuracy in NPC patients treated with PD-1/PD-L1 inhibitors.
Asunto(s)
Antígeno B7-H1 , Inhibidores de Puntos de Control Inmunológico , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nomogramas , Humanos , Masculino , Femenino , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/patología , Persona de Mediana Edad , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Adulto , Curva ROC , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Anciano , Modelos LogísticosRESUMEN
BACKGROUND: Acute myeloid leukemia (AML) is a hematological malignancy with high molecular and clinical heterogeneity, and is the most common type of acute leukemia in adults. Due to limited treatment options, AML is prone to relapse and has a poor prognosis. Excision repair cross-complementing 3 (ERCC3) is an important member of nucleotide excision repair (NER) that is overexpressed in types of solid cancers and potentially regarded as a prognostic factor. However, its role in AML remains unclear. The purpose of this study was to explore ERCC3 expression and functions in AML. METHODS: The Cancer Genome Atlas (TCGA) and GEO (Gene Expression Omnibus) were used to test the accuracy of ERCC3 expression levels for AML diagnosis. Using online databases and R packages, we also explored the signaling pathway, epigenetic regulation, infiltration of immune cells, clinical prognostic value, and ceRNA network in AML. RESULTS: Our results revealed that ERCC3 expression was increased in AML and that high ERCC3 expression had good value for disease-free survival and overall survival in AML patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We found that ERCC3 and co-expressed genes were mainly involved in chemical carcinogenesis/reactive oxygen species, ubiquitin-mediated protein degradation and oxidative phosphorylation. In addition, almost all the m6A-related coding genes (except GF2BP1) were positively associated with ERCC3 expression. We also constructed a ceRNA regulatory network containing ERCC3 in AML and identified 6 pairs of ceRNA networks, indicating that ERCC3 expression is regulated by a noncoding RNA system. CONCLUSION: This study demonstrated that ERCC3 was overexpressed in AML and that high ERCC3 expression can be considered a biomarker conducive to allo-HSCT in AML patients.
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Epigénesis Genética , Leucemia Mieloide Aguda , Adulto , Humanos , Leucemia Mieloide Aguda/patología , Pronóstico , Enfermedad Crónica , Reparación del ADNRESUMEN
Vancomycin is a first-line drug for treating methicillin-resistant Staphylococcus aureus. Thrombocytopenia is a rare adverse reaction to vancomycin treatment, and there are no reports of vancomycin-induced thrombocytopenia (VIT) in infants. We describe the case of a 3-month-old girl who was diagnosed with purulent meningitis. After 13 days of treatment with vancomycin, her platelet count reduced to 8 × 109/L. Vancomycin was discontinued, and intravenous methylprednisolone was administered. The platelet count returned to normal after 4 days. Patients, especially young children, receiving vancomycin for a long clinical course should undergo careful monitoring of laboratory indicators and blood tests.
Asunto(s)
Trombocitopenia/inducido químicamente , Vancomicina/efectos adversos , Femenino , Humanos , Lactante , Meningitis Bacterianas/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Trombocitopenia/diagnóstico , Factores de Tiempo , Vancomicina/uso terapéuticoRESUMEN
Abstract Vancomycin is a first-line drug for treating methicillin-resistant Staphylococcus aureus. Thrombocytopenia is a rare adverse reaction to vancomycin treatment, and there are no reports of vancomycin-induced thrombocytopenia (VIT) in infants. We describe the case of a 3-month-old girl who was diagnosed with purulent meningitis. After 13 days of treatment with vancomycin, her platelet count reduced to 8 × 109/L. Vancomycin was discontinued, and intravenous methylprednisolone was administered. The platelet count returned to normal after 4 days. Patients, especially young children, receiving vancomycin for a long clinical course should undergo careful monitoring of laboratory indicators and blood tests.
Asunto(s)
Humanos , Femenino , Lactante , Trombocitopenia/inducido químicamente , Vancomicina/efectos adversos , Trombocitopenia , Trombocitopenia/diagnóstico , Índice de Severidad de la Enfermedad , Vancomicina/uso terapéutico , Meningitis Bacterianas/tratamiento farmacológicoRESUMEN
We have evaluated for the first time the impact of a solvent/detergent (S/D) treatment on the quality and in vivo neutralization potency of horse-derived whole IgG antivenom used in the treatment of viperid snake bite envenoming in Central America. The S/D treatment by 1% tri (n-butyl) phosphate (TnBP) - 1% Triton X-45 at 22-25 degrees C was applied either on starting plasma or on purified immunoglobulins. The S/D agents were removed from both fractions by extractions with oil. S/D-treated plasma was subjected to caprylic acid precipitation to purify the immunoglobulins. Products were formulated, sterile-filtered, and filled into 10-mL vials, stored at 5+/-3 degrees C, and subjected to routine quality controls, SDS-PAGE, determination of anti-Bothrops asper venom antibody titre by ELISA, in vivo B. asper venom-neutralization potency tests, and safety test, comparatively with an antivenom manufactured by caprylic acid fractionation without S/D treatment. Results indicate that these conditions of S/D treatment on purified immunoglobulin yielded an antivenom of high turbidity that induced weight loss in animals. In contrast, antivenom fractionated from the S/D-treated plasma had physico-chemical and biological characteristics indistinguishable from those of the non-S/D-treated antivenom. S/D treatment of horse plasma may be considered to increase the viral safety of antivenoms.
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Antivenenos/efectos de los fármacos , Detergentes/farmacología , Inmunoglobulina G/efectos de los fármacos , Pruebas de Neutralización/métodos , Solventes/farmacología , Algoritmos , Animales , Antivenenos/efectos adversos , Antivenenos/inmunología , Antivenenos/uso terapéutico , Bothrops/inmunología , Venenos de Crotálidos/inmunología , Caballos/sangre , Caballos/inmunología , Inmunoglobulina G/química , Pruebas de Neutralización/normas , Octoxinol/farmacología , Organofosfatos/farmacología , Control de Calidad , Mordeduras de Serpientes/tratamiento farmacológicoRESUMEN
The potency of the immune response has still to be harnessed effectively to combat human cancers. However, the discovery of T-cell targets in melanomas and other tumors has raised the possibility that cancer vaccines can be used to induce a therapeutically effective immune response against cancer. The targets, cancer-testis (CT) antigens, are immunogenic proteins preferentially expressed in normal gametogenic tissues and different histological types of tumors. Therapeutic cancer vaccines directed against CT antigens are currently in late-stage clinical trials testing whether they can delay or prevent recurrence of lung cancer and melanoma following surgical removal of primary tumors. CT antigens constitute a large, but ill-defined, family of proteins that exhibit a remarkably restricted expression. Currently, there is a considerable amount of information about these proteins, but the data are scattered through the literature and in several bioinformatic databases. The database presented here, CTdatabase (http://www.cta.lncc.br), unifies this knowledge to facilitate both the mining of the existing deluge of data, and the identification of proteins alleged to be CT antigens, but that do not have their characteristic restricted expression pattern. CTdatabase is more than a repository of CT antigen data, since all the available information was carefully curated and annotated with most data being specifically processed for CT antigens and stored locally. Starting from a compilation of known CT antigens, CTdatabase provides basic information including gene names and aliases, RefSeq accession numbers, genomic location, known splicing variants, gene duplications and additional family members. Gene expression at the mRNA level in normal and tumor tissues has been collated from publicly available data obtained by several different technologies. Manually curated data related to mRNA and protein expression, and antigen-specific immune responses in cancer patients are also available, together with links to PubMed for relevant CT antigen articles.