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1.
Front Immunol ; 15: 1293931, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469299

RESUMO

Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients. Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients. Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients. Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Biomarcadores , Linfócitos T CD8-Positivos/patologia , Células Matadoras Naturais/patologia , Lenalidomida/uso terapêutico , Linfoma Difuso de Grandes Células B/patologia , Recidiva Local de Neoplasia/patologia , Resposta Patológica Completa
2.
Sci Rep ; 12(1): 14873, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050339

RESUMO

A rising number of authors are drawing evidence on the diagnostic capacity of specific volatile organic compounds (VOCs) resulting from some body fluids. While cancer incidence in society is on the rise, it becomes clear that the analysis of these VOCs can yield new strategies to mitigate advanced cancer incidence rates. This paper presents the methodology implemented to test whether a device consisting of an electronic nose inspired by a dog's olfactory system and olfactory neurons is significantly informative to detect breast cancer (BC). To test this device, 90 human urine samples were collected from control subjects and BC patients at a hospital. To test this system, an artificial intelligence-based classification algorithm was developed. The algorithm was firstly trained and tested with data resulting from gas chromatography-mass spectrometry (GC-MS) urine readings, leading to a classification rate of 92.31%, sensitivity of 100.00%, and specificity of 85.71% (N = 90). Secondly, the same algorithm was trained and tested with data obtained with our eNose prototype hardware, and class prediction was achieved with a classification rate of 75%, sensitivity of 100%, and specificity of 50%.


Assuntos
Neoplasias da Mama , Compostos Orgânicos Voláteis , Animais , Inteligência Artificial , Neoplasias da Mama/diagnóstico , Cães , Nariz Eletrônico , Feminino , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Compostos Orgânicos Voláteis/análise
3.
Clin Cancer Res ; 28(17): 3658-3668, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35727601

RESUMO

PURPOSE: New therapeutic options are needed in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide-based schedules can reverse rituximab refractoriness in lymphoma. PATIENTS AND METHODS: In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with the following schedule: lenalidomide 10 mg Days (D)1-14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1, gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg D1-3, up to 6 cycles (induction phase), followed by lenalidomide 10 mg (or last lenalidomide dose received) D1-21 every 28 days (maintenance phase). Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and monitorization of key circulating immune biomarkers (EU Clinical Trials Register number: EudraCT 2014-001620-29). RESULTS: After a median follow-up of 37 months, ORR was 60.2% [37.1% complete responses (CR) and 23.1% partial responses (PR)]. Median OS was 12 months (47 vs. 6 months in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in CR vs. no CR). In the primary refractory population, ORR was 45.5% (21.2% CR and 24.3% PR). Most common grade 3-4 adverse events were thrombocytopenia (60.2%), neutropenia (60.2%), anemia (26.9%), infections (15.3%), and febrile neutropenia (14.1%). Complete responses were associated with a sharp decrease in circulating myeloid-derived suppressor cells and regulatory T cells. CONCLUSIONS: R2-GDP schedule is feasible and highly active in R/R DLBCL, including the primary refractory population. Immune biomarkers showed differences in responders versus progressors.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Humanos , Lenalidomida/efeitos adversos , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Rituximab/uso terapêutico , Resultado do Tratamento
4.
J Immunother Cancer ; 9(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34158317

RESUMO

BACKGROUND: The search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumors, jeopardizing antitumor immunosurveillance. In this work, we have studied blood levels of these immunosuppressive cells in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), prior to and along the course of the experimental rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP) schedule, as a translational substudy of the R2-GDP-GOTEL trial (EudraCT Number: 2014-001620-29), which included lenalidomide as an immunomodulator. METHODS: Blood samples were taken before treatment, at cycle 3 and end of induction. Samples were analyzed by flow cytometry. Non-parametric tests were used. Mann-Whitney U test was used to compare basal cells distributions, and Wilcoxon test was considered to compare cells distribution at different times. Spearman test was performed to measure the degree of association between cell populations. RESULTS: In this study, MDSC and Treg circulating concentration was found increased in all patients compared with a healthy control group and decreased after treatment only in patients with longest overall survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes expressing Programmed Death-1 (PD-1) were increased in peripheral blood from patients and decreased on the treatment, whereas activated T lymphocytes increased after therapy in those with better overall survival. CONCLUSIONS: In conclusion, blood concentration of MDSCs and Treg cells may be good prognostic markers for overall survival after 2 years in R/R DLBCL. These results point to a possible role of these elements in the immunosuppression of these patients, as assessed by the circulating activated and inhibited T lymphocytes, and therefore, they may be considered as therapeutic targets in DLBCL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/imunologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Células Supressoras Mieloides/metabolismo , Linfócitos T Reguladores/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Estudos de Casos e Controles , Ensaios Clínicos como Assunto , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/imunologia , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/efeitos dos fármacos , Receptor de Morte Celular Programada 1/metabolismo , Análise de Sobrevida , Linfócitos T Reguladores/efeitos dos fármacos , Resultado do Tratamento
5.
Leuk Lymphoma ; 55(1): 51-5, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23573825

RESUMO

Relapse is the main cause of therapeutic failure in follicular lymphoma (FL). We set out to evaluate the role of consolidation with Yttrium-90 ibritumomab tiuxetan in patients with intermediate- and high-risk FL after four cycles of CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) and two cycles of CHOP. Thirty patients were included. The overall response rate after consolidation therapy was 93%. Of the 18 patients who presented with a partial response after induction treatment, 11 had a complete response after consolidation treatment. The complete clinical response rate was 76.6%. The most important grade 3-4 toxicity was hematological, with 46% thrombopenia and 56% neutropenia. With a median follow-up of 26 months, the means for progression-free survival and overall survival were not reached. Our data support consolidation with Yttrium-90 ibritumomab tiuxetan as an effective treatment, which provides long progression-free and overall survival, in first line after a response to induction treatment in patients with intermediate- and high-risk FL.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Quimioterapia de Consolidação , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologia , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Quimioterapia de Indução , Linfoma Folicular/mortalidade , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Prognóstico , Fatores de Risco , Rituximab , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
6.
Clin Transl Oncol ; 8(3): 208-12, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16648121

RESUMO

AIM AND BACKGROUND: Intestinal alkalization could prevent irinotecan associated diarrhea modulating some chemical equilibria between irinotecan metabolites. The aim of this study was to evaluate the efficacy of this procedure in advanced gastrointestinal cancer patients (GICP). MATERIALS AND METHOD: In this prospective study advanced GICP, receiving irinotecan based chemotherapy regimens, were well trained to add sodium bicarbonate to the water intake in order to accomplish intestinal alkalization. RESULTS: A total of twenty four advanced GICP were enrolled. Grade III-IV diarrhea has been observed in four patients (16%), some of whom had several risk factors for diarrhea. Only one out of seventeen colorectal cancer patients, receiving the irinotecan combination as first line therapy, had grade III-IV diarrhea. No side effects of the procedure have been appreciated. CONCLUSIONS: Intestinal alkalization may be effective as a preventive treatment for irinotecan associated diarrhea in chemotherapy regimens used in GICP. This procedure deserves further investigation.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Camptotecina/análogos & derivados , Diarreia/induzido quimicamente , Diarreia/prevenção & controle , Neoplasias Gastrointestinais/tratamento farmacológico , Bicarbonato de Sódio/uso terapêutico , Adulto , Idoso , Camptotecina/efeitos adversos , Feminino , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
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