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1.
Rinsho Ketsueki ; 62(5): 398-406, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34108321

RESUMO

It has been 20 years since the clinical introduction of rituximab, a monoclonal anti-CD20 antibody. Rituximab combination chemotherapy has substantially improved the prognosis of nearly all B-cell malignancies. Twenty years following the clinical introduction of rituximab, the era of molecular targeted agents and development of novel molecular targeted agents, including monoclonal antibody based on the molecular pathology, has been promoted. In recent years, CAR-T therapy and immune checkpoint inhibitors have been introduced in the clinical practice of malignant lymphoma. On the other hand, there are many histopathological subtypes that cannot directly receive the benefits of immunotherapy, and sufficient improvement in the prognosis of these subtypes is not seen. Therefore, further elucidation of molecular pathology and development of novel molecular targeted agents are crucial for the improvement of their prognosis. In this review, molecular targeted agents introduced into clinical practice in recent years, which revolutionized the treatment of malignant lymphoma, and molecular targeted agents expected to be introduced in clinical practice in the near future are discussed.


Assuntos
Antineoplásicos , Linfoma , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Humanos , Linfoma/tratamento farmacológico , Terapia de Alvo Molecular , Rituximab/uso terapêutico
2.
Anticancer Res ; 41(5): 2647-2652, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952495

RESUMO

BACKGROUND/AIM: Primary adrenal lymphoma (PAL) is rare and aggressive. The aim of this retrospective study was to compare the results of surgery and chemotherapy compared to chemotherapy alone for the treatment of this condition. PATIENTS AND METHODS: Sixteen patients, 10 men and 6 women of a median age of 63 years (IQR=56-70.5 years), admitted for the treatment of PAL, were retrospectively reviewed. Six patients (37.5%) underwent surgical resection of the mass followed by CHOP (cyclophosphamide, doxorubicin, vincristine, bleomycin and prednisone) - based chemotherapy (Group A). Ten patients (62.5%) underwent chemotherapy alone, consisting of CHOP alone in one case and Rituximab-CHOP (R-CHOP) in 9 cases (Group B). As primary study endpoints of the study, overall survival (OS) and progression-free survival (PFS) were considered. RESULTS: At two years follow-up, OS was 50% in Group A and 60% in group B (p=0.69). The PFS was 50% in group A and 30% in group B (p=0.42). CONCLUSION: PAL exhibits overall a dismal prognosis. Chemotherapy remains the most appropriate treatment, although unable to ensure long-term survival. Surgery combined with chemotherapy is ineffective in improving survival and may, at best, have a limited role in relieving the pain related to the local mass effect.


Assuntos
Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/cirurgia , Linfoma/tratamento farmacológico , Linfoma/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos de Coortes , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos
4.
Lancet Haematol ; 8(6): e433-e445, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34048682

RESUMO

BACKGROUND: Novel approaches are required to improve outcomes in relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma. We aimed to evaluate camidanlumab tesirine, an anti-CD25 antibody-drug conjugate, in this patient population. METHODS: This was a phase 1, dose-escalation (part 1), dose-expansion (part 2), multicentre trial done in 12 hospital sites (seven in the USA and five in the UK). Adults (≥18 years old) with pathologically confirmed relapsed or refractory classical Hodgkin lymphoma or non-Hodgkin lymphoma, an Eastern Cooperative Oncology Group performance status 0-2, who had no therapies available to them with established clinical benefit for their disease stage were enrolled. Camidanlumab tesirine was administered intravenously (3-150 µg/kg) once every 3 weeks. Primary objectives were to assess dose-limiting toxicity, determine maximum tolerated dose and recommended expansion dose(s), and assess safety of camidanlumab tesirine. Safety was assessed in all treated patients; antitumour activity was assessed in patients with one or more valid baseline and post-baseline disease assessment and in those who had disease progression or died after first study-drug dose. This trial was registered with ClinicalTrials.gov, NCT02432235. FINDINGS: Between Oct 5, 2015, and Jun 30, 2019, 133 patients were enrolled (77 [58%] had classical Hodgkin lymphoma and 56 (42%) had non-Hodgkin lymphoma). Median follow-up was 9·2 months (IQR 4·2-14·3). Eight dose-limiting toxicities were reported in five (6%) of 86 patients who were evaluable; the maximum tolerated dose was not reached. The recommended doses for expansion were 30 µg/kg and 45 µg/kg for patients with classical Hodgkin lymphoma and 80 µg/kg for patients with T-cell non-Hodgkin lymphomas. No recommended doses for expansion were defined for B-cell non-Hodgkin lymphomas. Grade 3 or worse treatment-emergent adverse events (reported by ≥10% of the 133 patients) included increased γ-glutamyltransferase (20 [15%] patients), maculopapular rash (16 [12%]), and anaemia (15 [11%]); 74 (56%) patients had serious treatment-emergent adverse events, most commonly pyrexia (16 [12%]). One (1%) fatal treatment-emergent adverse event and two (2%) deaths outside the reporting period were considered at least possibly study-drug related. Antitumoural activity was seen in classical Hodgkin and non-Hodgkin lymphomas; notably in all patients with classical Hodgkin lymphoma, the overall response was 71% (95% CI 60-81). INTERPRETATION: These results warrant evaluation of camidanlumab tesirine as a potential treatment option for relapsed or refractory lymphoma, particularly in patients with classical Hodgkin lymphoma. FUNDING: ADC Therapeutics.


Assuntos
Imunoconjugados/uso terapêutico , Linfoma/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , Esquema de Medicação , Exantema/etiologia , Exantema/patologia , Feminino , Febre/etiologia , Febre/patologia , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Imunoconjugados/efeitos adversos , Subunidade alfa de Receptor de Interleucina-2/imunologia , Estimativa de Kaplan-Meier , Linfoma/mortalidade , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Curr Protoc ; 1(4): e96, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33861502

RESUMO

In the hemato-oncology field, remarkable scientific progress has been achieved, primarily propelled by the discovery of new technologies, improvement in genomics, and novel in vitro and in vivo models. The establishment of multiple cell line collections and the development of instrumental mouse models enhanced our ability to discover effective therapeutics. However, cancer models that faithfully mimic individual cancers are still imperfect. Patient-derived tumor xenografts (PDTXs) have emerged as a powerful tool for identifying the mechanisms which drive tumorigenesis and for testing potential therapeutic interventions. The recognition that PDTXs can maintain many of the donor samples' properties enabled the development of new strategies for discovering and implementing therapies. Described in this article are protocols for the generation and characterization of lymphoma PDTXs that may be used as the basis of shared procedures. Universal protocols will foster the model utilization, enable the integration of public and private repositories, and aid in the development of shared platforms. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Tissue handling and cryopreservation of primary and PDTX samples Basic Protocol 2: Performing tumor implant in immunocompromised mice PDTX models Alternate Protocol 1: Intra-medullary femoral injection Alternate Protocol 2: Intravenous injection Alternate Protocol 3: Intraperitoneal injection Support Protocol 1: Phenotypical characterization of PDTXs by flow cytometry Support Protocol 2: Biological and molecular characterization of PDTX tumors by PCR detection of IGK, IGH, and TCR rearrangements Basic Protocol 3: Harvesting PDTX-derived tumor cells for ex vivo experiments Basic Protocol 4: In vivo testing of multiple compounds in a PDTX mouse model.


Assuntos
Descoberta de Drogas , Linfoma , Animais , Modelos Animais de Doenças , Xenoenxertos , Linfoma/tratamento farmacológico , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Curr Oncol ; 28(2): 1249-1255, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809772

RESUMO

The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) coronavirus has generated a pandemic, in which there are population groups at higher risk and who are potentially fatal victims of the disease. Cancer patients have been considered a group with special susceptibility, particularly patients with lung tumour involvement and haematological neoplasms. The Spanish Lymphoma Oncology Group (GOTEL) carried out a multicenter study of SARS-CoV-2 seroprevalence in patients with lymphoma. Results: A total of 150 patients were included between 22 May and 11 June 2020. The mean age was 65 years (range 17-89), 70 women (46.5%) and 80 men (53, 5%). At the time of diagnosis of lymphoma, 13 cases were stage I (9%), 27 (18%) stage II, 37 (24.5%) stage III, and 73 (48.5%) stage IV, while 6.6% had a primary extranodal origin. A total of 10 cases with positive serology for SARS-CoV-2 were identified, which is a prevalence of 6% in this population. None of the patients required intensive care unit management and all fully recovered from the infection. Conclusion: IgG antibody seroprevalence in lymphoma patients appears similar to that of the general population and does not show greater aggressiveness.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/epidemiologia , Linfoma/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoglobulina G/sangue , Linfoma/sangue , Linfoma/tratamento farmacológico , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Espanha/epidemiologia , Adulto Jovem
7.
Molecules ; 26(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806585

RESUMO

Rituximab is a chimeric immunoglobulin G1-kappa (IgG1κ) antibody targeting the CD20 antigen on B-lymphocytes. Its applications are various, such as for the treatment of chronic lymphoid leukemia or non-Hodgkin's lymphoma in oncology, and it can also be used in the treatment of certain autoimmune diseases. Several studies support the interest in therapeutic drug monitoring to optimize dosing regimens of rituximab. Thus, two different laboratories have developed accurate and reproductive methods to quantify rituximab in human plasma: one using liquid chromatography quadripolar tandem mass spectrometer (LC-MS/MS) and the other, liquid chromatography orbitrap tandem mass spectrometer (LC-MS/HRMS). For both assays, quantification was based on albumin depletion or IgG-immunocapture, surrogate peptide analysis, and full-length stable isotope-labeled rituximab. With LC-MS/MS, the concentration range was from 5 to 500 µg/mL, the within- and between-run precisions were <8.5%, and the limit of quantitation was 5 µg/mL. With LC-MS/HRMS, the concentration range was from 10 to 200 µg/mL, the within- and between-run accuracy were <11.5%, and the limit of quantitation was 2 µg/mL. Rituximab plasma concentrations from 63 patients treated for vasculitis were compared. Bland-Altman analysis and Passing-Bablok regression showed the interchangeability between these two methods. Overall, these methods were robust and reliable and could be applied to routine clinical samples.


Assuntos
Antineoplásicos Imunológicos/sangue , Cromatografia Líquida/métodos , Linfoma/sangue , Rituximab/sangue , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Espectrometria de Massas em Tandem/métodos , Vasculite/sangue , Antineoplásicos Imunológicos/administração & dosagem , Monitoramento de Medicamentos , Humanos , Marcação por Isótopo , Linfoma/tratamento farmacológico , Linfoma/patologia , Reprodutibilidade dos Testes , Rituximab/administração & dosagem , Vasculite/tratamento farmacológico , Vasculite/patologia
8.
Medicine (Baltimore) ; 100(9): e24706, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655935

RESUMO

RATIONALE: A few cases of optic neuropathy presumed to be caused by vincristine have been reported. However, none described multimodal imaging findings. Here, we report abnormal magnetic resonance imaging (MRI) and optical coherence tomography (OCT) findings in a putative case of vincristine-induced optic neuropathy. PATIENT CONCERNS: A 9-year-old boy with Burkett lymphoma who had had no visual problems noticed blurred vision in both eyes 22 days after the first maintenance therapy for lymphoma; the blurred gradually worsened. At that time, the best-corrected visual acuity was 20/200 and 20/100 in the right and left eyes, respectively. DIAGNOSES: Blood and imaging workup, and cerebrospinal fluid and genetic analyses, were performed; these included fundus photography, OCT, and MRI. We found no plausible cause of the optic neuropathy other than vincristine. INTERVENTIONS: The scheduled chemotherapy was stopped, and the patient was managed with high-dose corticosteroids. However, as there was no improvement, plasma exchange was then performed. OUTCOMES: Three days after the initial examination, the visual acuity in both eyes was only light perception and projection. Signal intensity was abnormally high on 3-dimensional T2-weighted turbo spin echo and T2-weighted MRI images. Optic disc atrophy progressed to "total pallor"; thinning of the ganglion cell-inner plexiform and retinal nerve fiber layers also progressed. The patient was followed up for 7 months but showed no improvement in vision. There were no treatment-related complications. LESSONS: We conclude that vincristine can cause optic neuropathy, and clinicians need to be alert to the possibility of optic neuropathy in any patient prescribed this agent.OCT and MRI may help to diagnose optic neuropathy in pediatric patients. Periodic ophthalmologic examinations, including an OCT scan, may be useful.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Imageamento por Ressonância Magnética , Doenças do Nervo Óptico/diagnóstico por imagem , Tomografia de Coerência Óptica , Vincristina/efeitos adversos , Criança , Humanos , Linfoma/tratamento farmacológico , Masculino , Imagem Multimodal , Doenças do Nervo Óptico/induzido quimicamente
9.
Toxicol Appl Pharmacol ; 418: 115491, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33737021

RESUMO

Pyrazole or 1,2-Diazole is a five-membered heteroaromatic ring with two nitrogen atoms which is widely used in pharmacological research and organic synthesis. Several natural and synthetic pyrazole derivatives possess anti-cancer potential and some of them have underwent clinical trials. In this aspect, an investigation into the efficiency of the pyrazole nucleus to inhibit the growth and progression of various cancer cell lines/ experimental tumours would help in giving a better clarity to the anti-cancer behaviour of pyrazole containing drugs. This paper investigates the efficiency of pyrazole against Dalton's Lymphoma Ascites (DLA) cell line. Pyrazole inhibited the growth of DLA cells in vitro by committing them towards apoptosis. In vitro results were consistent in DLA induced murine solid tumour in vivo systems. Drug-treatment improved survival, reduced tumour loads, stabilized body weights and improved the haematological and serum biochemical parameters of DLA solid tumour bearing mice, thereby improving their overall survivability. Drug administration contained the aggravation of solid tumour by targeted downregulation of Cyclin-D1 and Ki-67. In addition, the mRNA expression levels of anti-apoptotic genes, BCL-2 and BCL-XL were downregulated in solid tumours, corroborating the in vitro results that pyrazole encourage apoptotic cell death in DLA cells. The new findings establish pyrazole as a potential anti-cancer drug candidate. The results must encourage future investigations into the efficacy of the drug against various cancer types.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ascite/tratamento farmacológico , Ciclina D1/metabolismo , Antígeno Ki-67/metabolismo , Linfoma/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Pirazóis/farmacologia , Proteína bcl-X/metabolismo , Animais , Ascite/genética , Ascite/metabolismo , Ascite/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Linfoma/genética , Linfoma/metabolismo , Linfoma/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-bcl-2/genética , Transdução de Sinais , Proteína bcl-X/genética
10.
JAMA Netw Open ; 4(2): e2036321, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33533931

RESUMO

Importance: Rituximab is among the most frequently used immunotherapies in pediatrics. Few studies have reported long-term adverse events associated with its use for children. Objective: To describe the use of rituximab and to assess whether its use is associated with short- or long-term adverse events, infections, or time to immune reconstitution in a diverse group of young people. Design, Setting, and Participants: This retrospective cohort study included 468 patients aged younger than 21 years who received rituximab for diverse indications between October 1, 2010, and December 31, 2017, at Texas Children's Hospital, a large pediatric referral hospital. Patterns of adverse events, infections, and immune recovery are described. Data analyses were conducted from December 2019 to June 2020. Exposure: One or more doses of rituximab. Main Outcomes and Measures: Adverse drug events (eg, anaphylaxis), incidence of mild and severe infections, and time to recovery of B lymphocyte subset counts and immunoglobulin levels. Survival models and logistic regression analyses and were used to identify associated risk factors of infectious and noninfectious adverse drug events. Results: We identified 468 patients receiving at least 1 dose of rituximab. The total follow-up time was 11 713 person-months. Of the 468 patients, 293 (62.6%) were female, the median (interquartile range) age at receipt of dose was 14.3 (9.9-16.8) years, and 209 (44.7%) were self-reported White Hispanic. Adverse events associated with rituximab infusion occurred in 72 patients (15.4%), and anaphylaxis occurred in 17 patients (3.6%). Long-term adverse events, such as prolonged neutropenia and leukoencephalopathy, were absent. Infections occurred in 224 patients (47.9%); 84 patients (17.9%) had severe infections, and 3 patients (0.6%) had lethal infections. Concurrent use of intravenous chemotherapy, treatment of systemic lupus erythematosus, neutropenia, and use of intravenous immunoglobulin were associated with increased risk of infection. Among 135 patients (28.8%) followed up to B cell count recovery, CD19+ or CD20+ cell numbers normalized in a median of 9.0 months (interquartile range, 5.9-14.4 months) following rituximab use; 48 of 95 patients (51%) evaluated beyond a year had low-for-age B cell counts. Recovery of CD27+ memory B cell number occurred in a median of 15.7 months (interquartile range, 6.0-22.7 months). Among patients with normal baseline values, low immunoglobulin G (IgG) levels developed in 67 of 289 patients (23.2%) and low IgM levels in 118 of 255 patients (40.8%); of these patients evaluated beyond 12 months from rituximab, 16 of 117 (13.7%) had persistently low IgG and 37 (33.9%) of 109 had persistently low IgM. Conclusions and Relevance: Rituximab is well tolerated among young people and is associated with few serious adverse events, but infections are common, corresponding to a prolonged period of B cell count recovery often lasting for longer than a year. Further examination of strategies to prevent infections following rituximab should be pursued.


Assuntos
Anafilaxia/epidemiologia , Fatores Imunológicos/efeitos adversos , Infecções/epidemiologia , Reação no Local da Injeção/epidemiologia , Neutropenia/epidemiologia , Rituximab/efeitos adversos , Adolescente , Agamaglobulinemia/induzido quimicamente , Agamaglobulinemia/epidemiologia , Anafilaxia/induzido quimicamente , Doenças Autoimunes do Sistema Nervoso/tratamento farmacológico , Linfócitos B , Criança , Pré-Escolar , Estudos de Coortes , Encefalite/tratamento farmacológico , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Infecções/induzido quimicamente , Leucoencefalopatia Multifocal Progressiva/epidemiologia , Efeitos Adversos de Longa Duração/induzido quimicamente , Efeitos Adversos de Longa Duração/epidemiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Contagem de Linfócitos , Linfoma/tratamento farmacológico , Masculino , Esclerose Múltipla/tratamento farmacológico , Síndrome Nefrótica/tratamento farmacológico , Neutropenia/induzido quimicamente , Razão de Chances , Modelos de Riscos Proporcionais , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
11.
Hematology ; 26(1): 249-255, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33618613

RESUMO

BACKGROUND: Primary gastrointestinal lymphoma (PGIL), an uncommon subtype of lymphoma, accounts for 1%-4% of gastrointestinal cancers. This study, therefore, aimed to investigate the current 10-year epidemiology and outcomes of PGIL. METHODS: This retrospective study involved a hospital-based chart review to analyze the epidemiology, clinical features, predisposing factors, and clinical outcomes of patients diagnosed with, and treated for, PGIL. Data covering 10 years was collected of Thai patients aged ≥ 15 years who had been diagnosed as PGIL with pathological confirmation and treated at Siriraj Hospital, Thailand. RESULTS: A total of 175 PGIL patients were enrolled. Their median age was 60 years (range, 20-98), with a male predominance. The stomach was the most common site of gastrointestinal (GI) organ involvement by lymphoma (38.9%), followed by the small intestine (23.4%) and multiple sites of GI involvement (23.4%). Diffuse large B-cell lymphoma (DLBCL) had the highest proportion of PGIL, accounting for 61.1%. The median patient follow-up time was 13.9 months (range: 0-104.9 months). The median overall survival (OS) of PGIL patients was not reached during the 10 years, with a 5-year OS of 64.4%. The probability of having a better OS was demonstrated in patients with a good performance status who received a rituximab-containing regimen. CONCLUSIONS: The stomach was the most common site of lymphoma involvement in the GI tract, with DLBCL accounting for the highest proportion of those patients. The long-term survival outcome was significantly improved in patients with good performance status and rituximab exposure. Trial registrationNot applicable.


Assuntos
Neoplasias Gastrointestinais/epidemiologia , Linfoma/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Comorbidade , Gerenciamento Clínico , Feminino , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/mortalidade , Humanos , Linfoma/diagnóstico , Linfoma/tratamento farmacológico , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Tailândia/epidemiologia , Resultado do Tratamento , Adulto Jovem
12.
BMC Surg ; 21(1): 38, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446156

RESUMO

BACKGROUND: Chemotherapy can cause thymic atrophy and reduce T-cell output in cancer patients. However, the thymus in young adult patients has regenerative potential after chemotherapy, manifesting as thymic hyperplasia which can be easily mistaken as residual disease or recurrence in patients suffering lymphoma. CASE PRESENTATION: This study reports a case of lymphoma in a young female adult who was initially diagnosed with an anterior mediastinal mass, and was found to have soft tissue occupying the anterior mediastinum repeatedly after chemotherapy, suggesting a lymphoma residue or disease progression. From discussions by a multi-disciplinary team (MDT), the anterior mediastinal mass of the patient was considered unknown and might be thymus tissue or tumor tissue, and it was eventually identified as thymus tissue via histopathology. CONCLUSIONS: The anterior mediastinal mass appearing after chemotherapy in patients with lymphoma can be considered as enlarged thymus, and such phenomenon is frequent in young adult patients who undergo chemotherapy or autologous hematopoietic stem cell transplantation. Additionally, detection of thymic output cells in peripheral blood might be a feasible approach to differentiate thymic hyperplasia from lymphoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfoma/tratamento farmacológico , Neoplasias do Mediastino/tratamento farmacológico , Hiperplasia do Timo/induzido quimicamente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Erros de Diagnóstico , Progressão da Doença , Feminino , Humanos , Linfoma/patologia , Neoplasias do Mediastino/patologia , Mediastino/diagnóstico por imagem , Mediastino/patologia , Recidiva Local de Neoplasia , Timo/patologia , Hiperplasia do Timo/diagnóstico , Hiperplasia do Timo/diagnóstico por imagem , Hiperplasia do Timo/patologia
13.
Radiology ; 298(1): 231-236, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33347397

RESUMO

History A 25-year-old woman was referred to our breast clinic for assessment of a palpable mass in her left breast that developed quickly in 2 weeks. She denied any associated fever, chills, redness, or pain. She had no relevant medical or surgical history; no evidence of recent pregnancy, abortion, or breastfeeding; and no family history of breast cancer. Clinical examination enabled confirmation of a firm mass occupying the retroareolar region and the outer quadrant of the left breast with no skin retraction, edema, or erythema. There was no evidence of enlarged axillary lymph nodes. US of the left breast, bilateral breast MRI, and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT were performed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Diagnóstico por Imagem/métodos , Linfoma/diagnóstico por imagem , Linfoma/tratamento farmacológico , Adulto , Biópsia , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/patologia , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Linfoma/patologia , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prednisona/uso terapêutico , Compostos Radiofarmacêuticos , Rituximab/uso terapêutico , Resultado do Tratamento , Ultrassonografia Mamária/métodos , Vincristina/uso terapêutico
14.
Mater Sci Eng C Mater Biol Appl ; 119: 111648, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33321684

RESUMO

Lymphoma is a well-known malignant tumor in the human body. Although many anticancer drugs have been developed to improve the survival rate of patients, about 40% of patients continue to be recurrent or refractory, a key issue needing remedy. Therefore, it is necessary to identify alternative treatments to reduce the disease's mortality. To this effect, a new type of anti-lymphoma nanocomplex FA@RBCm-AgNPs was prepared using AgNPs as the core of nanoparticles along with the targeting molecule folic acid inserted erythrocyte membrane as the shell. The biomimetic properties of red blood cell membrane (RBCm) endow F-RAN with good biocompatibility as well as the ability to evade clearance of the reticuloendothelial system. In addition, F-RAN was modified with folic acid to actively and selectively identify tumor cells. In vivo and in vitro experiments demonstrate that F-RAN can inhibit lymphoma cells and induce apoptosis of stem cells while promoting apoptosis of lymphoma with no obvious side effects. Hence, F-RAN may serve as a new treatment for lymphoma.


Assuntos
Linfoma , Nanopartículas Metálicas , Nanopartículas , Apoptose , Biomimética , Linhagem Celular Tumoral , Humanos , Linfoma/tratamento farmacológico , Prata
16.
Front Immunol ; 11: 560244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33324393

RESUMO

The B-cell receptor (BCR) is a key player of the adaptive immune system. It is a unique part of immunoglobulin (Ig) molecules expressed on the surface of B cells. In case of many B-cell lymphomas, the tumor cells express a tumor-specific and functionally active BCR, also known as idiotype. Utilizing the idiotype as target for lymphoma therapy has emerged to be demanding since the idiotype differs from patient to patient. Previous studies have shown that shark-derived antibody domains (vNARs) isolated from a semi-synthetic CDR3-randomized library allow for the rapid generation of anti-idiotype binders. In this study, we evaluated the potential of generating patient-specific binders against the idiotype of lymphomas. To this end, the BCRs of three different lymphoma cell lines SUP-B8, Daudi, and IM-9 were identified, the variable domains were reformatted and the resulting monoclonal antibodies produced. The SUP-B8 BCR served as antigen in fluorescence-activated cell sorting (FACS)-based screening of the yeast-displayed vNAR libraries which resulted after three rounds of screening in the enrichment of antigen-binding vNARs. Five vNARs were expressed as Fc fusion proteins and consequently analyzed for their binding to soluble antigen using biolayer interferometry (BLI) revealing binding constants in the lower single-digit nanomolar range. These variants showed specific binding to the parental SUP-B8 cell line confirming a similar folding of the recombinantly expressed proteins compared with the native cell surface-presented BCR. First initial experiments to utilize the generated vNAR-Fc variants for BCR-clustering to induce apoptosis or ADCC/ADCP did not result in a significant decrease of cell viability. Here, we report an alternative approach for a personalized B-cell lymphoma therapy based on the construction of vNAR-Fc antibody-drug conjugates to enable specific killing of malignant B cells, which may widen the therapeutic window for B-cell lymphoma therapy.


Assuntos
Anticorpos Anti-Idiotípicos/farmacologia , Especificidade de Anticorpos , Antineoplásicos Imunológicos/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Tubarões/imunologia , Animais , Anticorpos Anti-Idiotípicos/genética , Especificidade de Anticorpos/imunologia , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Linhagem Celular Tumoral , Expressão Gênica , Biblioteca Gênica , Humanos , Imunoconjugados/genética , Imunoconjugados/farmacologia , Imunofenotipagem , Linfoma/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Receptores de Antígenos de Linfócitos B/sangue , Receptores de Antígenos de Linfócitos B/genética , Proteínas Recombinantes de Fusão/genética , Tubarões/genética
17.
Int J Hematol ; 112(6): 807-816, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32880824

RESUMO

CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) -/+ rituximab (R) is the standard chemotherapeutic regimen for aggressive lymphoma, but is insufficient for aggressive lymphoma with adverse prognostic factors. Dose-adjusted (DA)-EPOCH (etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisolone) -/+ R demonstrates excellent efficacy against some aggressive lymphoma. Thus, we conducted a retrospective study to evaluate the feasibility and efficacy of this therapy in clinical practice. We enrolled 149 patients from 17 institutions diagnosed between 2007 and 2015. The median follow-up period for survivors was 27 months (range 0.2-123). The complete response (CR) rate of newly diagnosed patients was 79% (95% CI 68-87%). All patients were hospitalized to receive this therapy and 94% of patients also received granulocyte-colony-stimulating factor support. There were no treatment-related deaths. Febrile neutropenia (FN) and grade 3 or 4 infection occurred in 55% and 28% of patients, respectively. There were no significant differences in FN or infection between young (≤ 65 years) and elderly patients (> 65 years). In newly diagnosed diffuse large B-cell lymphoma-not otherwise specified patients (n = 46), the CR rate was 80% (95% CI 64-91%) and the 2-year OS rate was 81% (95% CI 66-90%). In the present study, DA-EPOCH -/+ R exhibited excellent efficacy and feasibility for aggressive lymphoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma/tratamento farmacológico , Rituximab/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/etiologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Estudos de Viabilidade , Neutropenia Febril/epidemiologia , Neutropenia Febril/etiologia , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto Jovem
18.
J Environ Pathol Toxicol Oncol ; 39(3): 247-260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865916

RESUMO

The anticancer activity of malvidin was studied in Dalton's lymphoma ascites (DLA)-induced solid and ascitic tumor mice models. Malvidin is a natural compound belonging to the family of O-methylated anthocyanidin and plays a predominant role in regulating both short- and long-term cellular activities. Animals were injected with DLA cells (1.5 × 106 cells/animal) to induce solid and ascitic tumors. The administration of malvidin (5 mg/kg bw and 10 mg/kg bw) was carried out for 10 consecutive days from the day of tumor induction for both solid and ascitic tumors. Cyclophosphamide, CTX (25 mg/kg bw), used as the standard drug, was also administered for 10 consecutive days. Treatment with malvidin showed a significant reduction in tumor volume and elevated white blood cell (WBC) count when compared to the DLA-bearing control animals. The treatment also maintained the body weight and hemoglobin level, and decreases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) were also noted. This investigation also reported the decreased levels of cellular glutathione (GSH) in ascitic tumor groups. Malvidin reduced inflammatory mediator and cytokine levels, such as tumor necrosis factor level alpha (TNF-α) and interleukin-6 (IL-6), which serve as molecular targets for cancer prevention. A decrease in the level of reactive oxygen species (ROS), like nitric oxide (NO), was observed. Histopathological examination revealed altered morphological changes in tumor tissue and the alleviation of hepatic architecture due to DLA. Immunohistochemical analysis revealed the inhibition of iNOS. This study demonstrated that malvidin exhibited significant in vivo antitumor activity and that it was reasonably imputable to its increasing endogenous mechanism. We accent the pertinence of malvidin as a potential naturally derived drug target for tumor control.


Assuntos
Antocianinas/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Ascite/tratamento farmacológico , Citocinas/sangue , Linfoma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Antocianinas/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Ascite/metabolismo , Ascite/patologia , Biomarcadores/sangue , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Citocinas/metabolismo , Linfoma/metabolismo , Linfoma/patologia , Masculino , Camundongos , Transplante de Neoplasias , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Estresse Oxidativo/imunologia
20.
Ann Hematol ; 99(10): 2429-2436, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32839869

RESUMO

Patients receiving vinca alkaloids for hematological malignancies frequently experience constipation that is unresponsive to laxatives. Research on treatment of vinca alkaloid-induced constipation is limited. This study aimed to determine whether the chloride channel activator lubiprostone ameliorates vinca alkaloid-induced constipation in patients with hematological malignancies. In this retrospective cohort study, vinca alkaloid-induced constipation (grade ≥ 3 using the Common Terminology Criteria for Adverse Events) was investigated in patients treated for hematological malignancies between July 2014 and June 2019 who had already been prescribed osmotic laxatives and additionally received either a stimulant laxative or lubiprostone. Univariate and multivariate analyses were performed to identify the risk factors for persistent constipation after introduction of the second laxative. A propensity score model was used to match 67 patients taking a stimulant laxative and 67 treated with lubiprostone, and the occurrence of intractable constipation was compared between groups. Overall, 203 patients were included, among whom 50 (25%) had constipation. On multivariate analysis, body mass index, opioid use, and addition of lubiprostone were independently associated with constipation. Patients treated with lubiprostone were significantly less likely to experience intractable constipation than did those treated with stimulant laxatives (10% vs. 34%, P = 0.002). Moreover, post-constipation diarrhea was significantly less frequent among patients treated with lubiprostone (42% vs. 63%, P = 0.024). Lubiprostone was more effective than stimulant laxatives at treating vinca alkaloid-induced intractable constipation in patients with hematological malignancies, and its use could enable safe vinca alkaloid chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Agonistas dos Canais de Cloreto/uso terapêutico , Constipação Intestinal/tratamento farmacológico , Neoplasias Hematológicas/tratamento farmacológico , Lubiprostona/uso terapêutico , Linfoma/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Alcaloides de Vinca/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Constipação Intestinal/induzido quimicamente , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Avaliação de Medicamentos , Quimioterapia Combinada , Famotidina/uso terapêutico , Feminino , Humanos , Laxantes/farmacologia , Laxantes/uso terapêutico , Óxido de Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Entorpecentes/efeitos adversos , Prednisona/administração & dosagem , Pontuação de Propensão , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Senosídeos/uso terapêutico , Alcaloides de Vinca/administração & dosagem , Vincristina/administração & dosagem
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