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1.
Cancer Med ; 13(4): e7064, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38457256

RESUMO

INTRODUCTION: Although anti-CD19 chimeric antigen receptor (CAR) T cell therapy was approved as a very effective salvage strategy in relapsed/refractory (R/R) B cell lymphoma, the experience in R/R gastrointestinal (GI) lymphoma is still insufficient. METHODS: We summarized the efficacy and side effects of anti-CD19 CAR T-cell therapy in 12 patients with R/R GI lymphoma. Based on literature, the R/R GI lymphoma patients were divided into subgroups with different characteristics: Bulky/No bulky disease, Gastric/Gastrointestinal involvement, Gastrointestinal/Combined extra-gastrointestinal lesions, Ulcer/Lumps or nodules type, With/without gastrointestinal bleeding. RESULTS: The objective response rate (ORR) was 66.67% in these 12 patients. The ORR was 83.33% in no bulky disease group, 80.00% in gastric involvement group, 100.00% in ulcer type group, and 80.00% in no gastrointestinal bleeding group. The CR rate was 33.33% in these 12 patients. The CR was 50.0% in no bulky disease group, 60.00% in gastric involvement group, and 80.00% in ulcer type group. The PFS and OS rate of the 12 patients at 6 months after infusion were 54.55% and 58.33%, respectively. The overall survival (OS) at 6 months was higher in no bulky disease group. There was no difference of the OS or the progression free survival (PFS) at 6 months between the other groups. The mean peak of CAR-T cells and Cytokine Release Syndrome (CRS) grade were higher in gastrointestinal lesions group. The mean peak of IFN-γ and CRS grade were higher in gastrointestinal bleeding group. Four out of six patients in group of gastrointestinal lesions group were patient with high tumor burden. Patients with gastrointestinal involvement only were at higher risk for gastrointestinal bleeding. CONCLUSIONS: The ORR and CR of high tumor load, gastrointestinal involvement, lumps or nodules type and gastrointestinal bleeding group were lower. The CRS grade was higher in gastrointestinal lesions group and in gastrointestinal bleeding group. Patients with gastrointestinal involvement only were at higher risk for gastrointestinal bleeding.


Assuntos
Neoplasias Gastrointestinais , Linfoma de Células B , Linfoma , Humanos , Imunoterapia Adotiva/efeitos adversos , Receptores de Antígenos de Linfócitos T , Linfócitos T , Úlcera/etiologia , Linfoma/terapia , Linfoma de Células B/etiologia , Neoplasias Gastrointestinais/terapia , Neoplasias Gastrointestinais/etiologia , Síndrome da Liberação de Citocina/etiologia , Antígenos CD19 , Hemorragia Gastrointestinal
2.
Medicine (Baltimore) ; 103(10): e37248, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457543

RESUMO

INTRODUCTION: In rare occasions, coxsackievirus infections can cause serious illness, such as encephalitis and myocarditis. The immunotherapies of cancer could increase the risk of myocarditis, especially when applying immune checkpoint inhibitors. Herein, we report a rare case of Coxsackie B virus-induced myocarditis in a patient with a history of lymphoma. CASE PRESENTATION: A 32-year-old woman was admitted to the hospital with recurrent fever for more than 20 days, and she had a history of lymphoma. Before admission, the positron emission tomography/computed tomography result indicated that the patient had no tumor progression, and she was not considered the cancer-related fever upon arriving at our hospital. Patient's red blood cell, platelet count, and blood pressure were decreased. In addition, she had sinus bradycardia and 3 branch blocks, which was consistent with acute high lateral and anterior wall myocardial infarction. During hospitalization, the patient had recurrent arrhythmia, repeated sweating, poor mentation, dyspnea, and Coxsackie B virus were detected in patient's blood samples by pathogen-targeted next-generation sequencing. The creatine kinase, creatine kinase MB, and N-terminal pro-brain natriuretic peptide were persistently elevated. Consequently, the patient was diagnosed with viral myocarditis induced by Coxsackie B virus, and treated with acyclovir, gamma globulin combined with methylprednisolone shock therapy, trimetazidine, levosimendan, sildenan, continuous pump pressors with m-hydroxylamine, entecavir, adefovir, glutathione, pantoprazole, and low-molecular-weight heparin. Her symptoms worsened and died. CONCLUSION: We reported a case with a history of lymphoma presented with fever, myocardial injury, who was ultimately diagnosed with Coxsackie B virus-induced myocarditis. Moreover, pathogen-targeted next-generation sequencing indeed exhibited higher sensitivity compared to mNGS in detecting Coxsackie B virus.


Assuntos
Infecções por Coxsackievirus , Linfoma , Miocardite , Viroses , Humanos , Feminino , Adulto , Miocardite/diagnóstico , Miocardite/etiologia , Enterovirus Humano B , Infecções por Coxsackievirus/complicações , Infecções por Coxsackievirus/diagnóstico , Febre
3.
Rinsho Ketsueki ; 65(2): 84-89, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38448003

RESUMO

A 63-year-old man with adult T-cell leukemia-lymphoma underwent allogeneic bone marrow transplantation from an HLA-matched unrelated donor. On day 17 after transplantation, chest computed tomography (CT) showed nodules in the lower lobes of both lungs, and invasive pulmonary aspergillosis (IPA) was suspected. Treatment with liposomal amphotericin B was started, and improvement of infectious lesions was confirmed with CT on day 28. The antifungal agent was changed to voriconazole on day 52 because of progressive renal dysfunction. Disorders of consciousness and paralysis of the left upper and lower extremities developed on day 61. Brain CT showed subcortical hemorrhage in the right parietal and occipital lobes, and the patient died on day 62. An autopsy revealed filamentous fungi, suspected to be Aspergillus, in the pulmonary nodules and a ruptured cerebral aneurysm. Although IPA occurs in 10% of transplant recipients, vigilant monitoring for mycotic cerebral aneurysms is required to prevent hematogenous dissemination of Aspergillus, which is associated with a high mortality rate.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Aneurisma Intracraniano , Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/terapia , Leucemia-Linfoma de Células T do Adulto/complicações , Leucemia-Linfoma de Células T do Adulto/terapia , Transplante de Medula Óssea
4.
Sci Transl Med ; 16(737): eadh1988, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38446900

RESUMO

Despite the advances in cancer treatment achieved, for example, by the CD20 antibody rituximab, an urgent medical need remains to optimize the capacity of such antibodies to induce antibody-dependent cellular cytotoxicity (ADCC) that determines therapeutic efficacy. The cytokine IL-15 stimulates proliferation, activation, and cytolytic capacity of NK cells, but broad clinical use is prevented by short half-life, poor accumulation at the tumor site, and severe toxicity due to unspecific immune activation. We here report modified immunocytokines consisting of Fc-optimized CD19 and CD20 antibodies fused to an IL-15 moiety comprising an L45E-E46K double mutation (MIC+ format). The E46K mutation abrogated binding to IL-15Rα, thereby enabling substitution of physiological trans-presentation by target binding and thus conditional IL-15Rßγ stimulation, whereas the L45E mutation optimized IL-15Rßγ agonism and producibility. In vitro analysis of NK activation, anti-leukemia reactivity, and toxicity using autologous and allogeneic B cells confirmed target-dependent function of MIC+ constructs. Compared with Fc-optimized CD19 and CD20 antibodies, MIC+ constructs mediated superior target cell killing and NK cell proliferation. Mouse models using luciferase-expressing human NALM-6 lymphoma cells, patient acute lymphoblastic leukemia (ALL) cells, and murine EL-4 lymphoma cells transduced with human CD19/CD20 as targets and human and murine NK cells as effectors, respectively, confirmed superior and target-dependent anti-leukemic activity. In summary, MIC+ constructs combine the benefits of Fc-optimized antibodies and IL-15 cytokine activity and mediate superior NK cell immunity with potentially reduced side effects. They thus constitute a promising new immunotherapeutic approach shown here for B cell malignancies.


Assuntos
Interleucina-15 , Linfoma , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal , Anticorpos , Antígenos CD19 , Citocinas , Fragmentos Fc das Imunoglobulinas
5.
BMJ Open ; 14(3): e078320, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453197

RESUMO

OBJECTIVES: The role of the Controlling Nutritional Status (CONUT) scores in predicting the prognosis of lymphoma cases has been extensively explored, with no consistent results. The present meta-analysis focused on accurately evaluating whether CONUT could be used to predict the prognosis of lymphoma cases and its clinicopathological value. DESIGN: The present meta-analysis was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The prognostic significance of CONUT to overall survival (OS) and progression-free survival (PFS) in lymphoma was estimated by calculating pooled HRs with 95% CIs. The relationship between CONUT and clinicopathological characteristics was measured based on pooled ORs with 95% CIs. DATA SOURCES: PubMed, Web of Science, Embase and Cochrane Library databases were comprehensively searched from inception through 24 March 2023. STATISTICAL METHODS: Either a random-effects model or a fixed-effects model was selected depending on the level of heterogeneity among the included studies. RESULTS: This meta-analysis enrolled seven articles, containing 2060 patients with lymphoma. According to the pooled analysis, a higher CONUT score significantly predicted poor OS (HR=1.94, 95% CI 1.46 to 2.57, p<0.001) as well as poorer PFS (HR=1.51, 95% CI 1.04 to 2.20, p=0.031). Furthermore, according to the combined analysis, a higher CONUT score was significantly associated with Ann Arbor stages III-IV (OR=3.75, 95% CI 2.96 to 4.75, p<0.001), an Eastern Cooperative Oncology Group performance status of 2-4 (OR=5.14, 95% CI 3.97 to 6.65, p<0.001), high-intermediate/high National Comprehensive Cancer Network International Prognostic Index (OR=8.05, 95% CI 5.11 to 12.66, p<0.001), B symptoms (OR=4.97, 95% CI 2.89 to 8.52, p<0.001), extranodal disease (OR=3.25, 95% CI 2.24 to 4.70, p<0.001), bone marrow involvement (OR=4.86, 95% CI 3.25 to 7.27, p<0.001) and elevated lactate dehydrogenase levels (OR=3.21, 95% CI 2.37 to 4.34, p<0.001). CONCLUSIONS: According to our results, higher CONUT scores were significantly associated with poor OS and PFS in lymphoma.


Assuntos
Linfoma , Estado Nutricional , Humanos , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
6.
Ann Med ; 56(1): 2329130, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38489405

RESUMO

In recent years, the incidence and mortality rates of lymphoma have gradually increased worldwide. Tumorigenesis and drug resistance are closely related to intracellular inflammatory pathways in lymphoma. Therefore, understanding the biological role of inflammatory pathways and their abnormal activation in relation to the development of lymphoma and their selective modulation may open new avenues for targeted therapy of lymphoma. The biological functions of inflammatory pathways are extensive, and they are central hubs for regulating inflammatory responses, immune responses, and the tumour immune microenvironment. However, limited studies have investigated the role of inflammatory pathways in lymphoma development. This review summarizes the relationship between abnormal activation of common inflammatory pathways and lymphoma development to identify precise and efficient targeted therapeutic options for patients with advanced, drug-resistant lymphoma.


Inflammatory pathways directly or indirectly regulate the TME and are closely related to the development of lymphoma.This review was conducted to elucidate the connection between inflammatory pathways and the tumorigenesis and drug resistance of several common lymphomas.Overall, targeting abnormally activated molecules upstream and downstream of lymphoma inflammatory pathways in the future is expected to be a new target for lymphoma treatment.


Assuntos
Linfoma , Humanos , Linfoma/etiologia , Linfoma/metabolismo , Transformação Celular Neoplásica , Microambiente Tumoral
7.
J Int Med Res ; 52(3): 3000605241233988, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38483129

RESUMO

Gastric metastasis from breast cancer has a high rate of misdiagnosis and missed diagnosis. Data of patients who had gastric metastasis from breast cancer were retrieved from our hospital between 2014 and 2020. The gastric metastasis from breast cancer incidence was 0.04% (5/14,169 cases of breast cancer). Four patients had invasive lobular carcinoma, and the other patient had invasive ductal carcinoma. The time from the initial diagnosis of breast cancer to the appearance of gastric metastasis ranged from 0 to 12 years. One patient's endoscopic presentation was similar to mucosal-associated lymphoid tissue lymphoma and presented with gastric mucosal congestion and edema, widened wrinkles, mixed color fading, and redness. The initial pathological diagnosis of this patient was mucosal-associated lymphoid tissue lymphoma, and breast cancer was finally confirmed by immunohistochemistry. Hormonal receptors were highly expressed in four patients with primary and metastasis lesions and were negative in one patient. Human epidermal growth factor receptor 2 was negative in all patients. Mammaglobin and GATA3 were positive in all patients. In conclusion, the gastric metastasis of breast cancer incidence rate is low, and misdiagnosis can lead to insufficient or excessive treatment. Multiple biopsies and immunohistochemistry should be performed to diagnose gastric metastasis of breast cancer.


Assuntos
Neoplasias da Mama , Carcinoma Lobular , Linfoma , Neoplasias Gástricas , Humanos , Feminino , Neoplasias da Mama/patologia , Carcinoma Lobular/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia
8.
Lancet Rheumatol ; 6(4): e216-e225, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38437852

RESUMO

BACKGROUND: Sjögren's disease is a heterogenous autoimmune disease with a wide range of symptoms-including dryness, fatigue, and pain-in addition to systemic manifestations and an increased risk of lymphoma. We aimed to identify distinct subgroups of the disease, using cluster analysis based on subjective symptoms and clinical and biological manifestations, and to compare the prognoses of patients in these subgroups. METHODS: This study included patients with Sjögren's disease from two independent cohorts in France: the cross-sectional Paris-Saclay cohort and the prospective Assessment of Systemic Signs and Evolution of Sjögren's Syndrome (ASSESS) cohort. We first used an unsupervised multiple correspondence analysis to identify clusters within the Paris-Saclay cohort using 26 variables comprising patient-reported symptoms and clinical and biological manifestations. Next, we validated these clusters using patients from the ASSESS cohort. Changes in disease activity (measured by the European Alliance of Associations for Rheumatology [EULAR] Sjögren's Syndrome Disease Activity Index [ESSDAI]), patient-acceptable symptom state (measured by the EULAR Sjögren's Syndrome Patient Reported Index [ESSPRI]), and lymphoma incidence during follow-up were compared between clusters. Finally, we compared our clusters with the symptom-based subgroups previously described by Tarn and colleagues. FINDINGS: 534 patients from the Paris-Saclay cohort (502 [94%] women, 32 [6%] men, median age 54 years [IQR 43-64]), recruited between 1999 and 2022, and 395 patients from the ASSESS cohort (370 [94%] women, 25 [6%] men, median age 53 years [43-63]), recruited between 2006 and 2009, were included in this study. In both cohorts, hierarchical cluster analysis revealed three distinct subgroups of patients: those with B-cell active disease and low symptom burden (BALS), those with high systemic disease activity (HSA), and those with low systemic disease activity and high symptom burden (LSAHS). During follow-up in the ASSESS cohort, disease activity and symptom states worsened for patients in the BALS cluster (67 [36%] of 186 patients with ESSPRI score <5 at month 60 vs 92 [49%] of 186 at inclusion; p<0·0001). Lymphomas occurred in patients in the BALS cluster (five [3%] of 186 patients; diagnosed a median of 70 months [IQR 42-104] after inclusion) and the HSA cluster (six [4%] of 158 patients; diagnosed 23 months [13-83] after inclusion). All patients from the Paris-Saclay cohort with a history of lymphoma were in the BALS and HSA clusters. This unsupervised clustering classification based on symptoms and clinical and biological manifestations did not correlate with a previous classification based on symptoms only. INTERPRETATION: On the basis of symptoms and clinical and biological manifestations, we identified three distinct subgroups of patients with Sjögren's disease with different prognoses. Our results suggest that these subgroups represent different heterogeneous pathophysiological disease mechanisms, stages of disease, or both. These findings could be of interest when stratifying patients in future therapeutic trials. FUNDING: Fondation pour la Recherche Médicale, French Ministry of Health, French Society of Rheumatology, Innovative Medicines Initiative 2 Joint Undertaking, Medical Research Council UK, and Foundation for Research in Rheumatology.


Assuntos
Linfoma , Síndrome de Sjogren , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Síndrome de Sjogren/diagnóstico , Estudos Prospectivos , Paris/epidemiologia , Estudos Transversais , Análise por Conglomerados , Linfoma/epidemiologia
9.
Neoplasma ; 71(1): 37-47, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38506031

RESUMO

Neuroblastoma is the most common extracranial solid tumor in children. The purpose of the present study is to detect the prognostic role and potential therapeutic efficacy of the T lymphoma invasion and metastasis 1 (Tiam1) in neuroblastoma. The overexpression of Tiam1 protein is frequently observed in neuroblastoma. Tiam1 expression is closely associated with adverse prognosis of neuroblastoma and risk group classification. Knockdown of TIAM1 by lentivirus expressing short hairpin RNA against TIAM1 (sh-TIAM1) inhibited the proliferation, invasion and cell-cycle progression, and promoted apoptosis of the neuroblastoma cell lines SH-SY5Y and SK-N-AS. Additionally, downregulation of the differentiation-related protein expression and decreased Rac1 expression was observed in the sh-TIAM1-transfected SH-SY5Y cells. In vivo, nude mice bearing TIAM1 knockdown SH-SY5Y cells showed improved overall survival and tumor growth suppression. The results demonstrate that inhibition of Tiam1 expression is a potential strategy for targeted therapy in neuroblastoma.


Assuntos
Linfoma , Neuroblastoma , Animais , Camundongos , Criança , Humanos , Neuroblastoma/genética , Camundongos Nus , Transdução de Sinais , Proliferação de Células/genética , Linhagem Celular Tumoral
10.
Front Immunol ; 15: 1297893, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38504977

RESUMO

Introduction: Atherosclerosis is a lipid-driven inflammatory disease of the arterial wall, and the underlying cause of the majority of cardiovascular diseases. Recent advances in high-parametric immunophenotyping of immune cells indicate that T cells constitute the major leukocyte population in the atherosclerotic plaque. The E3 ubiquitin ligase Casitas B-lymphoma proto-oncogene-B (CBL-B) is a critical intracellular regulator that sets the threshold for T cell activation, making CBL-B a potential therapeutic target to modulate inflammation in atherosclerosis. We previously demonstrated that complete knock-out of CBL-B aggravated atherosclerosis in Apoe-/- mice, which was attributed to increased macrophage recruitment and increased CD8+ T cell activation in the plaque. Methods: To further study the T cell specific role of CBL-B in atherosclerosis, Apoe-/- CD4cre Cblb fl/fl (Cbl-bcKO) mice and Apoe-/-CD4WTCblbfl/fl littermates (Cbl-bfl/fl) were fed a high cholesterol diet for ten weeks. Results: Cbl-bcKO mice had smaller atherosclerotic lesions in the aortic arch and root compared to Cbl-bfl/fl, and a substantial increase in CD3+ T cells in the plaque. Collagen content in the plaque was decreased, while other plaque characteristics including plaque necrotic core, macrophage content, and smooth muscle cell content, remained unchanged. Mice lacking T cell CBL-B had a 1.4-fold increase in CD8+ T cells and a 1.8-fold increase in regulatory T cells in the spleen. Splenic CD4+ and CD8+ T cells had increased expression of C-X-C Motif Chemokine Receptor 3 (CXCR3) and interferon-γ (IFN-γ), indicating a T helper 1 (Th1)-like/effector CD8+ T cell-like phenotype. Conclusion: In conclusion, Cbl-bcKO mice have reduced atherosclerosis but show increased T cell accumulation in the plaque accompanied by systemic T cell activation.


Assuntos
Aterosclerose , Linfoma , Placa Aterosclerótica , Animais , Camundongos , Apolipoproteínas E/genética , Aterosclerose/metabolismo , Linfócitos T CD8-Positivos , Camundongos Knockout , Placa Aterosclerótica/patologia , Proteínas Proto-Oncogênicas c-cbl/genética , Proteínas Proto-Oncogênicas c-cbl/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
11.
Support Care Cancer ; 32(4): 238, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512692

RESUMO

PURPOSE: There has been little dedicated research on cancer-related cognitive impairment in patients with aggressive lymphoma. We describe and compare patients' cognitive function with that of healthy controls and patients' wellbeing and distress with general population values. We also explore associations between patients' neuropsychological test performance and self-reported cognitive function and distress. METHODS: Secondary analysis of data from a feasibility study of 30 patients with newly diagnosed aggressive lymphoma and 72 healthy controls. Patients completed neuropsychological tests and self-report measures before and 6-8 weeks after chemotherapy. Healthy controls completed neuropsychological tests and the FACT-Cog at enrolment and 6 months later. Mixed models were used to analyze neuropsychological test and FACT-Cog scores. One-sample t-tests were used to compare patients' self-reported wellbeing and distress with population norms. Associations were explored with Kendall's Tau b. RESULTS: Patients and healthy controls were well matched on socio-demographics. Differences between neuropsychological test scores were mostly large-sized; on average, patients' scores on measures of information processing speed, executive function, and learning and memory were worse both before and after chemotherapy (all p ≤ 0.003). The same pattern was observed for impact of perceived cognitive impairment on quality-of-life (both p < 0.001). Patients' physical and emotional wellbeing scores were lower than population norms both before and after chemotherapy (all p ≤ 0.018). Associations between neuropsychological performance and other measures were mostly trivial (all p > 0.10). CONCLUSION: For many patients with aggressive lymphoma, impaired neuropsychological test performance and impact of perceived impairments on quality-of-life precede chemotherapy and are sustained after chemotherapy. Findings support the need for large-scale longitudinal studies with this population to better understand targets for interventions to address cognitive impairments.


Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Linfoma , Neoplasias , Humanos , Transtornos Cognitivos/psicologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Cognição , Linfoma/complicações , Testes Neuropsicológicos
12.
Sci Rep ; 14(1): 6764, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514636

RESUMO

EBV-infected lymphoma has a poor prognosis and various treatment strategies are being explored. Reports suggesting that B cell lymphoma can be induced by epigenetic regulation have piqued interest in studying mechanisms targeting epigenetic regulation. Here, we set out to identify an epigenetic regulator drug that acts synergistically with doxorubicin in EBV-positive lymphoma. We expressed the major EBV protein, LMP1, in B-cell lymphoma cell lines and used them to screen 100 epigenetic modifiers in combination with doxorubicin. The screening results identified TCP, which is an inhibitor of LSD1. Further analyses revealed that LMP1 increased the activity of LSD1 to enhance stemness ability under doxorubicin treatment, as evidenced by colony-forming and ALDEFLUOR activity assays. Quantseq 3' mRNA sequencing analysis of potential targets regulated by LSD1 in modulating stemness revealed that the LMP1-induced upregulation of CHAC2 was decreased when LSD1 was inhibited by TCP or downregulated by siRNA. We further observed that SOX2 expression was altered in response to CHAC2 expression, suggesting that stemness is regulated. Collectively, these findings suggest that LSD1 inhibitors could serve as promising therapeutic candidates for EBV-positive lymphoma, potentially reducing stemness activity when combined with conventional drugs to offer an effective treatment approach.


Assuntos
Linfoma de Células B , Linfoma , Humanos , Herpesvirus Humano 4/genética , Lisina/metabolismo , Epigênese Genética , Linfoma/genética , Linfoma de Células B/genética , Histona Desmetilases/metabolismo , Doxorrubicina/farmacologia , Linhagem Celular Tumoral
13.
Cancer Med ; 13(5): e7056, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38477498

RESUMO

BACKGROUND: Non-Hodgkin lymphoma (NHL) accounts for 90% of all malignant lymphomas. This study aimed to evaluate the global incidence, mortality, associated risk factors, and temporal trends of NHL by sex, age, and country. METHODS: Data from 185 countries globally were used for analysis. NHL incidence and mortality were collected via the GLOBOCAN (2020), CI5 series I-X, WHO mortality database, the Nordic Cancer Registries, and the SEER Program. The WHO Global Health Observatory provided country-level, age-standardized prevalence of lifestyle and metabolic risk factors. Trends were examined and reported based on average annual percentage change (AAPC) calculated using Joinpoint regression analysis. Incidence and AAPC are based on data for the last 10 years across countries. RESULTS: Globally, age-standardized incidence and mortality rates for NHL were recorded at 5.8 and 2.6 per 100,000 individuals, respectively. At country-level, NHL incidence was significantly associated with various factors, including HDI (Human Development Index), GDP per capita, prevalence of tobacco and alcohol consumption, sedentary lifestyle, obesity, hypertension, diabetes and hypercholesterolaemia. Rising trend in NHL incidence was observed, with the highest increase recorded in Estonia (AAPCmale = 4.15, AAPCfemale = 5.14), Belarus (AAPCfemale = 5.13), and Lithuania (AAPCfemale = 4.68). While overall NHL mortality has been decreasing, certain populations experienced increased mortality over the decade. In Thailand, AAPC for mortality was 31.28% for males and 30.26% for females. Estonia saw an AAPC of 6.46% for males, while Slovakia experienced an AAPC of 4.24% for females. Colombia's AAPC was 1.29% for males and 1.51% for females. CONCLUSIONS: This study indicates a rising trend of NHL incidence over the past decade- particularly in developed countries, older males, and younger populations. Further research should investigate deeper insights into specific etiology and prognosis of NHL across subtypes, and potential contributors towards these epidemiologic trends.


Assuntos
Linfoma não Hodgkin , Linfoma , Humanos , Masculino , Feminino , Linfoma não Hodgkin/epidemiologia , Linfoma/epidemiologia , Incidência , Sistema de Registros , Fatores de Risco , Saúde Global
14.
Leuk Res ; 138: 107454, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38452534

RESUMO

Adult T-cell leukemia/lymphoma (ATL), caused by human T-cell leukemia virus type-1 (HTLV-1) infection, is a malignant hematologic cancer that remains difficult to cure. We herein established a biomarker identification strategy based on the total cell proteomics of cultured ATL cells to search for novel ATL biomarkers. Four protocols with a combination of selected conditions based on lysis buffers and addition agents for total cell proteomics were used for a differential analysis between the ATL cell group (consisting of 11 cell lines), HTLV-1-infected cell group (consisting of 6 cell lines), and HTLV-1-negative cell group (consisting of 6 cell lines). In the analysis, we identified 24 and 27 proteins that were significantly increased (ratio ≥2.0, p < 0.05) and decreased (ratio ≤ 0.5, p < 0.05), respectively, in the ATL group. Previously reported CCL3 and CD30/TNFRSF8 were confirmed to be among significantly increased proteins. Furthermore, correlation analysis between identified proteins and Tax suggested that RASSF2 and GORASP2 were candidates of novel Tax-regulated factors. The biomarker identification strategy established herein is expected to contribute to the identification of biomarkers for ATL and other diseases.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Humanos , Proteômica , Vírus Linfotrópico T Tipo 1 Humano/metabolismo , Biomarcadores , Digestão , Produtos do Gene tax/metabolismo , Proteínas da Matriz do Complexo de Golgi
15.
Cancer Med ; 13(6): e7050, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38506241

RESUMO

AIMS: T-follicular helper (TFH) cells are effector T-cells that are crucial for B-cell selection and differentiation. T-cell lymphomas derived from TFH cells have distinct characteristics. Additionally, in the World Health Organization (WHO) classification 5th edition, three lymphomas were introduced as independent disease entities with TFH cell origin. We aimed to investigate the clinicopathological features of adult T-cell leukemia/lymphoma (ATLL) with a TFH phenotype (TFHP). METHODS AND RESULTS: We performed TFH immunohistochemistry analysis of five biomarkers for the biopsy specimen, with TFHP being indicated by a positive result for more than two markers. Among 75 cases of ATLL, 37.3% of them showed TFHP. Compared with cases of ATLL without TFHP, cases of ATLL with TFHP showed higher C-reactive protein levels (p = 0.0219) and increased high endothelial venule proliferation (p = 0.024). However, there were no significant between-group differences in overall survival as well as other clinical and morphological findings. Furthermore, there was no significant between-group difference in TFH markers and FOXP3 expression. CONCLUSION: Some patients with ATLL may present a TFHP, which should not preclude the diagnosis of ATLL. Although presenting a TFHP does not affect prognosis, it is important to identify cases of ATLL with a TFHP since it may inform future treatment strategies.


Assuntos
Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Humanos , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/genética , Linfoma/patologia , Prognóstico , Fenótipo , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Auxiliares-Indutores/patologia
16.
Handb Clin Neurol ; 200: 419-429, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38494294

RESUMO

Paraneoplastic neurologic syndromes are rarely associated with hematologic malignancies. In their rarity, lymphomas are the diseases with more frequent paraneoplastic neurologic syndrome. High-risk antibodies are absent in most lymphoma-associated paraneoplastic neurologic syndromes, with the exception of antibodies to Tr/DNER in paraneoplastic cerebellar degeneration, mGluR5 in limbic encephalitis, and mGluR1 in some cerebellar ataxias. Peripheral nervous system paraneoplastic neurologic syndromes are rare and heterogeneous, with a prevalence of demyelinating polyradiculoneuropathy in non-Hodgkin lymphoma. Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) is a rare, paraneoplastic syndrome due to an underlying plasma cell disorder. The diagnosis is based on defined criteria, and vascular endothelial growth factor (VEGF), not an antibody, is considered a reliable diagnostic marker that also mirrors therapy response. As with the paraneoplastic neurologic syndromes in solid tumors, therapies rely on cancer treatment associated with immunomodulatory treatment with better response in PNS with antibodies to surface antigens. The best outcome is generally present in Ophelia syndrome/limbic encephalitis with anti-mGluR5 antibodies, with frequent complete recovery. Besides patients with isolated osteosclerotic lesions (where radiotherapy is indicated), hematopoietic stem-cell transplantation is the therapy of choice in patients with POEMS syndrome. In the paraneoplastic neurologic syndromes secondary to immune checkpoint inhibitors, discontinuation of the drug together with immunomodulatory treatment is recommended.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Encefalite Límbica , Linfoma , Síndromes Paraneoplásicas do Sistema Nervoso , Humanos , Fator A de Crescimento do Endotélio Vascular , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Síndromes Paraneoplásicas do Sistema Nervoso/patologia
18.
Signal Transduct Target Ther ; 9(1): 62, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448403

RESUMO

Natural killer T cell lymphoma (NKTCL) is highly aggressive, with advanced stage patients poorly responding to intensive chemotherapy. To explore effective and safe treatment for newly diagnosed advanced stage NKTCL, we conducted a phase II study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab (NCT04096690). Twenty-two patients with a median age of 51 years (range, 24-74) were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days, followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 days. The complete response and overall response rate after induction treatment were 59% (95%CI, 43-79%) and 68% (95%CI, 47-84%), respectively. With a median follow-up of 30 months, the 2 year progression-free and overall survival rates were 68% (95%CI, 45-83%) and 86% (95%CI, 63-95%), respectively. The most frequently grade 3/4 adverse events were neutropenia (32%, n = 7) and hypofibrinogenemia (18%, n = 4), which were manageable and led to no discontinuation of treatment. Tumor proportion score of PD-L1, peripheral blood high-density lipoprotein cholesterol, and apolipoprotein A-I correlated with good response, while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab treatment. In conclusion, the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed, advanced stage NKTCL. Dysregulated lipid profile and immunosuppressive signature contributed to treatment resistance, providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.


Assuntos
Anticorpos Monoclonais Humanizados , Asparaginase , Linfoma , Células T Matadoras Naturais , Polietilenoglicóis , Humanos , Receptor de Morte Celular Programada 1 , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem
19.
Ann Med ; 56(1): 2329140, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38470973

RESUMO

AIM: The combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor is one of the approaches for hematopoietic stem cell mobilization in patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), and Hodgkin's lymphoma (HL). This systematic review and meta-analysis aimed to determine the ability of G-CSF + plerixafor to mobilize peripheral blood (PB) CD34+ cells and examine its safety profile. METHODS: We performed a database search using the terms 'granulocyte colony stimulating factor', 'G-CSF', 'AMD3100', and 'plerixafor', published up to May 1, 2023. The methodology is described in further detail in the PROSPERO database (CRD42023425760). RESULTS: Twenty-three studies were included in this systematic review and meta-analysis. G-CSF + plerixafor resulted in more patients achieving the predetermined apheresis yield of CD34+ cells than G-CSF alone (OR, 5.33; 95%, 4.34-6.55). It was further discovered that G-CSF + plerixafor could mobilize more CD34+ cells into PB, which was beneficial for the next transplantation in both randomized controlled (MD, 18.30; 95%, 8.74-27.85) and single-arm (MD, 20.67; 95%, 14.34-27.00) trials. Furthermore, G-CSF + plerixafor did not cause more treatment emergent adverse events than G-CSF alone (OR, 1.25; 95%, 0.87-1.80). CONCLUSIONS: This study suggests that the combination of G-CSF and plerixafor, resulted in more patients with MM, NHL, and HL, achieving the predetermined apheresis yield of CD34+ cells, which is related to the more effective mobilization of CD34+ cells into PB.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Compostos Heterocíclicos , Linfoma não Hodgkin , Linfoma , Mieloma Múltiplo , Humanos , Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Fator Estimulador de Colônias de Granulócitos , Compostos Heterocíclicos/efeitos adversos , Linfoma/induzido quimicamente , Linfoma/terapia , Linfoma não Hodgkin/induzido quimicamente , Linfoma não Hodgkin/terapia , Células-Tronco Hematopoéticas , Transplante Autólogo , Benzilaminas , Transplante de Células-Tronco Hematopoéticas/métodos
20.
Otol Neurotol ; 45(4): 362-375, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437804

RESUMO

OBJECTIVE: To examine the otologic and neurotologic symptoms, physical examination findings, and imaging features secondary to hematologic malignancies. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, databases, including PubMed, Scopus, and CINAHL, were searched for articles including patients with otologic manifestations of leukemia, lymphoma and multiple myeloma. Data collected included patient and study demographics, specific hematologic malignancy, timing and classification of otologic symptoms, physical examination findings, imaging features and methods of diagnosis. Pooled descriptive analysis was performed. RESULTS: Two hundred seventy-two articles, of which 255 (93.8%) were case reports and 17 (6.2%) were case series, reporting on 553 patients were identified. Otologic manifestations were reported on 307 patients with leukemia, 204 patients with lymphoma and 42 patients with multiple myeloma. Hearing loss and unilateral facial palsy were the most common presenting symptoms for 111 reported subjects with leukemia (n = 46, 41.4%; n = 43, 38.7%) and 90 with lymphoma (n = 38, 42.2%; n = 39, 43.3%). Hearing loss and otalgia were the most common presenting symptoms for 21 subjects with multiple myeloma (n = 10, 47.6%; n = 6, 28.6%). Hearing loss and unilateral facial palsy were the most common otologic symptoms indicative of relapse in subjects with leukemia (n = 14, 43.8%) and lymphoma (n = 5, 50%). CONCLUSION: Hearing loss, facial palsy, and otalgia might be the first indication of a new diagnosis or relapse of leukemia, lymphoma, or multiple myeloma. Clinicians should have a heightened level of suspicion of malignant etiologies of otologic symptoms in patients with current or medical histories of these malignancies.


Assuntos
Paralisia de Bell , Surdez , Paralisia Facial , Perda Auditiva , Neoplasias Hematológicas , Leucemia , Linfoma , Mieloma Múltiplo , Humanos , Dor de Orelha , Paralisia Facial/complicações , Mieloma Múltiplo/complicações , Perda Auditiva/etiologia , Neoplasias Hematológicas/complicações , Surdez/complicações , Leucemia/complicações , Paralisia de Bell/complicações , Linfoma/complicações , Recidiva
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