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1.
Cancer Med ; 13(3): e6793, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38234210

RESUMO

AIM: Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is a heterogeneous disease that can be classified into the PTCL-TBX21 and PTCL-GATA3 subtypes. METHODS: In this study, we compared the clinicopathological features of PTCL-NOS in a Japanese cohort, classified using an IHC algorithm. RESULTS: One hundred patients with PTCL-NOS were categorized as having PTCL-TBX21 (n = 55), PTCL-GATA3 (n = 24), or PTCL-unclassified (n = 21). When comparing PTCL-TBX21 and PTCL-GATA3, PTCL-TBX21 showed significantly lower CD4 positivity (p = 0.047), lower counts of high endothelial venules (p = 0.032), and a tendency for a better response to initial treatment (p = 0.088). Gene expression analysis using the nCounter system showed higher expression of tumor immunity-related genes, such as PD-L1, LAG3, and IDO1, in PTCL-TBX21 than in PTCL-GATA3. PTCL-GATA3 had significantly worse overall survival (OS) than those with PTCL-TBX21 (p = 0.047), although a similar tendency was observed for progression-free survival (PFS) (p = 0.064). PTCL-GATA3 was a prognostic factor for OS in univariate analysis (HR 2.02; 95% CI, 1.09-3.77; p = 0.027), although multivariate analysis did not show significance (HR 2.07; 95% CI, 0.93-4.61; p = 0.074). In the PFS analysis, PTCL-GATA3 was an independent prognostic factor by univariate analysis (HR 1.96; 95% CI, 1.08-3.56; p = 0.027) and multivariate analysis (HR 2.34; 95% CI, 1.07-5.11; p = 0.032). CONCLUSION: The classification of PTCL-NOS into PTCL-TBX21 and PTCL-GATA3 is useful for predicting the prognosis of Japanese patients and stratifying the administration of tumor immune checkpoint inhibitors in clinical practice.


Assuntos
Algoritmos , Linfoma de Células T Periférico , Humanos , Japão , Perfilação da Expressão Gênica , Inibidores de Checkpoint Imunológico , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/genética , Fator de Transcrição GATA3/genética
2.
Rinsho Ketsueki ; 63(7): 759-763, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35922944

RESUMO

A 68-year-old male patient with lung adenocarcinoma, who was treated with chemotherapy and immune checkpoint inhibitors (ICIs), developed lymphadenopathy during treatment. His para-aortic lymph nodes increased to 2.0 cm in diameter. Both inguinal lymph nodes were 1.5 cm in diameter, and multiple hepatic masses appeared. After the ICI readministration, both inguinal lymph nodes increased to 2.0 cm in diameter, but the para-aortic lymph nodes and hepatic masses remained. Angioimmunoblastic T-cell lymphoma (AITL) diagnosis was established after the right inguinal lymph node biopsy, which was accompanied by an infiltration of Epstein-Barr virus (EBV)-encoded small ribonucleic acid-positive B-cells. After the ICI discontinuation, the inguinal lymph nodes decreased to 1.5 cm in diameter, but the para-aortic lymph nodes remained, and hepatic masses increased. Hepatic lesions were possibly lung cancer metastasis. The ICI administration and EBV reactivation were potentially associated with AITL development in the present case. The natural shrinkage of lymphoma after the ICI cessation implied the immunological mechanism like that of the methotrexate-related lymphoproliferative disease.


Assuntos
Infecções por Vírus Epstein-Barr , Linfadenopatia Imunoblástica , Neoplasias Pulmonares , Linfoma de Células T , Idoso , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/complicações , Linfonodos/patologia , Linfoma de Células T/tratamento farmacológico , Masculino
3.
J Clin Exp Hematop ; 61(1): 42-47, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33551436

RESUMO

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, also known as double-hit lymphoma, has been reported as refractory to R-CHOP therapy and requires more intensive regimens. However, intensive and safe regimens for patients with renal dysfunction are unknown. Herein, we report the successful use of DA-EPOCH-R therapy for double-hit lymphoma in a 64-year-old man with renal dysfunction. The patient had lymphoma-induced bilateral ureteral obstruction. Although renal dysfunction remained after removing the obstruction using R-CHOP therapy, we completed six cycles of DA-EPOCH-R therapy without any major adverse events. DA-EPOCH-R therapy may be a safe regimen for renal dysfunction patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Rearranjo Gênico , Nefropatias/complicações , Linfoma de Células B/genética , Linfoma de Células B/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Biomarcadores Tumorais , Biópsia , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Nefropatias/diagnóstico , Testes de Função Renal , Linfoma de Células B/complicações , Linfoma de Células B/diagnóstico , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas c-bcl-6 , Proteínas Proto-Oncogênicas c-myc/genética , Rituximab/administração & dosagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
4.
Int J Lab Hematol ; 42(6): 842-848, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32744749

RESUMO

INTRODUCTION: Adult T-cell leukemia/lymphoma (ATLL) is a malignant peripheral T-cell neoplasm associated with human T-cell leukemia virus type-1 (HTLV-1). The acute and lymphoma subtypes are regarded as aggressive ATLLs, and the overall survival (OS) of patients remains poor. Transforming acidic coiled-coil-containing protein 3 (TACC3) regulates microtubules, which are associated with cancer-related proteins overexpressed in various cancers. Such a relationship has not been reported in hematopoietic tumors, including ATLL. METHODS: We examined tissue microarrays of histological samples from 92 cases of aggressive ATLL and assessed clinical features, including TACC3 protein expression levels. RESULTS: Compared with TACC3-low, TACC3-high ATLL patients were significantly older (P < .001), with a tendency toward pleomorphic variant over other morphological classifications (P = .019). TACC3-high patients (median survival time [MST] 10.6 months, confidence interval [CI] [6.27-15.6]) had poorer OS compared to TACC3-low patients (MST 20 months, CI [9.43-38.5]) (P = .0168). Moreover, multivariate analysis on TACC3 expression levels suggests that TACC3-high is an independent significant prognostic factor (HR, 1.700; 95% CI, 1.037-2.753; P = .0355). CONCLUSION: Certain drugs that inhibit TACC3-overexpressing neoplastic cells are used clinically. Further studies might highlight a key role for TACC3 in the oncogenesis and progression of ATLL.


Assuntos
Regulação Leucêmica da Expressão Gênica , Leucemia-Linfoma de Células T do Adulto , Proteínas Associadas aos Microtúbulos/biossíntese , Proteínas de Neoplasias/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/metabolismo , Leucemia-Linfoma de Células T do Adulto/mortalidade , Leucemia-Linfoma de Células T do Adulto/patologia , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
5.
Pathol Int ; 70(9): 653-660, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32648273

RESUMO

Follicular T-cell lymphoma (FTCL) is considered to originate from follicular helper T-cell (Tfh) cells. Angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphomas with the Tfh phenotype, derived from Tfh cells, often harbor RHOA G17V mutation. We investigated whether RHOA mutations affect the clinicopathological features of FTCL. We performed deep sequencing and Sanger sequencing for RHOA exon 2 in 16 cases of FTCL. Nine cases showed RHOA mutations, including eight with c.G50T, p.Gly17Val and one with c.G50A, p.Gly17Glu, c.A52G, p.Lys18Glu, c.T102C, p.Tyr34Tyr and c.G145T, p.Asp49Tyr. Compared to the RHOA mutation-negative group, the RHOA mutation-positive group had a higher tendency for B-immunoblasts (P = 0.06), the AITL component (P = 0.09), and higher positive rate for CD10 (P = 0.09) and BCL6 (P = 0.09), and a significantly higher positive rate for CXCL13 (P = 0.04). Although not statistically significant, the RHOA mutation-positive group showed higher values for almost all characteristic AITL features. There was no significant difference in overall survival between RHOA mutation-positive and -negative groups. The RHOA mutation may play an important role in clinicopathological characteristics and lymphomagenesis of FTCL. A more detailed investigation is needed to highlight the importance of RHOA mutations in FTCL.


Assuntos
Linfoma de Células T , Mutação , Proteína rhoA de Ligação ao GTP/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Feminino , Humanos , Linfoma de Células T/genética , Linfoma de Células T/patologia , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/patologia , Masculino , Pessoa de Meia-Idade , Linfócitos T Auxiliares-Indutores/patologia
6.
Lab Invest ; 100(10): 1300-1310, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32472096

RESUMO

A pathological evaluation is one of the most important methods for the diagnosis of malignant lymphoma. A standardized diagnosis is occasionally difficult to achieve even by experienced hematopathologists. Therefore, established procedures including a computer-aided diagnosis are desired. This study aims to classify histopathological images of malignant lymphomas through deep learning, which is a computer algorithm and type of artificial intelligence (AI) technology. We prepared hematoxylin and eosin (H&E) slides of a lesion area from 388 sections, namely, 259 with diffuse large B-cell lymphoma, 89 with follicular lymphoma, and 40 with reactive lymphoid hyperplasia, and created whole slide images (WSIs) using a whole slide system. WSI was annotated in the lesion area by experienced hematopathologists. Image patches were cropped from the WSI to train and evaluate the classifiers. Image patches at magnifications of ×5, ×20, and ×40 were randomly divided into a test set and a training and evaluation set. The classifier was assessed using the test set through a cross-validation after training. The classifier achieved the highest levels of accuracy of 94.0%, 93.0%, and 92.0% for image patches with magnifications of ×5, ×20, and ×40, respectively, in comparison to diffuse large B-cell lymphoma, follicular lymphoma, and reactive lymphoid hyperplasia. Comparing the diagnostic accuracies between the proposed classifier and seven pathologists, including experienced hematopathologists, using the test set made up of image patches with magnifications of ×5, ×20, and ×40, the best accuracy demonstrated by the classifier was 97.0%, whereas the average accuracy achieved by the pathologists using WSIs was 76.0%, with the highest accuracy reaching 83.3%. In conclusion, the neural classifier can outperform pathologists in a morphological evaluation. These results suggest that the AI system can potentially support the diagnosis of malignant lymphoma.


Assuntos
Aprendizado Profundo , Diagnóstico por Computador/métodos , Linfoma/diagnóstico , Algoritmos , Diagnóstico por Computador/estatística & dados numéricos , Técnicas Histológicas , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Interpretação de Imagem Assistida por Computador/estatística & dados numéricos , Linfoma/diagnóstico por imagem , Linfoma/patologia , Linfoma Folicular/diagnóstico , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/patologia , Redes Neurais de Computação , Variações Dependentes do Observador , Patologistas , Pseudolinfoma/diagnóstico , Pseudolinfoma/diagnóstico por imagem , Pseudolinfoma/patologia
7.
Cancer Sci ; 111(7): 2608-2619, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32342603

RESUMO

The interaction between CD47 and signal-regulatory protein-α (SIRPα) inhibits phagocytosis, thus affecting the clinical outcomes of neoplastic diseases. Although CD47 upregulation is associated with poor prognosis in several malignancies, the effect of SIRPα expression and its coexpression with CD47 remains unclear. This study aimed to investigate the clinicopathologic effect of CD47 and SIRPα expression in diffuse large B-cell lymphoma (DLBCL). Immunostaining of 120 biopsy samples showed that CD47 is primarily expressed in tumor cells, whereas SIRPα is expressed in nonneoplastic stromal cells, mostly macrophages. CD47high cases showed higher MYC protein expression and lower MYC translocation. The SIRPαhigh cases presented significantly shorter overall survival (OS) and progression-free survival (PFS) than SIRPαlow cases in the activated B-cell (ABC) subtype of DLBCL (P = .04 and P = .02, respectively). Both CD47high and SIRPαhigh presented significantly shorter OS and PFS than other cases among all DLBCL patients (P = .01 and P = .004, respectively), and the ABC type (P = .04 and P = .008, respectively) but not the germinal center B-cell type. Both CD47high and SIRPαhigh yielded a constant independent prognostic value for OS and PFS in multivariate analysis (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.20-7.43; P = .02; and HR, 2.87; 95% CI, 1.42-5.85; P = .003, respectively). To the best of our knowledge, this is the first study to report that combinatorial CD47 and SIRPα expression is a potential independent prognostic factor for DLBCL. Evaluation of CD47 and SIRPα expression could be useful before CD47 blockade therapy.


Assuntos
Antígenos de Diferenciação/metabolismo , Antígeno CD47/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Receptores Imunológicos/metabolismo , Transdução de Sinais , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Diferenciação/genética , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores , Antígeno CD47/genética , Ciclofosfamida , Doxorrubicina , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Hibridização In Situ , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Pessoa de Meia-Idade , Prednisona , Prognóstico , Receptores Imunológicos/genética , Rituximab , Resultado do Tratamento , Vincristina
8.
Ann Hematol ; 99(5): 1093-1098, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32157421

RESUMO

Acute or lymphomatous type adult T cell leukemia/lymphoma (ATLL) is an aggressive hematopoietic malignancy with poor prognosis. We previously reported that programmed cell death ligand 1 (PD-L1) expression could predict ATLL outcomes. However, the roles of other immune checkpoint molecules remain largely unknown in ATLL. Our aim in this study was to explore the clinicopathological impacts of immune checkpoint molecules in ATLL. Immunohistochemistry was performed in 69 ATLL patients with antibodies against the following: PD-L1, programmed cell death ligand 2 (PD-L2), OX40, OX40 ligand (OX40L), CD137, CD137 ligand (CD137L), Galectin-9, T cell immunoglobulin mucin-3 (Tim-3), cytotoxic T lymphocyte associated protein-4 (CTLA-4), lymphocyte activating-3 (LAG-3), CD80, CD86, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), GITR ligand (GITRL), and programmed death-1 (PD-1). Immune checkpoint molecules were variably expressed on neoplastic and/or microenvironmental cells. Expression of PD-1, OX40L, Galectin-9, and PD-L1 was nearly mutually exclusive on neoplastic cells, suggesting that immune checkpoint pathways differ in patients. Microenvironmental expression of PD-L1, OX40L, and Tim-3 was significantly associated with better overall survival (log-rank test; P =0.0004, 0.0394, and 0.0279, respectively). Univariate and multivariate analyses with clinical prognostic factors identified microenvironmental expression of PD-L1 and OX40L, and age (> 70 years) as significant prognostic factors. This is the first comprehensive analysis of ATLL immune checkpoint molecules. Our results may provide information on new therapeutic strategies in ATLL.


Assuntos
Leucemia-Linfoma de Células T do Adulto , Proteínas de Neoplasias/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/metabolismo , Leucemia-Linfoma de Células T do Adulto/mortalidade , Leucemia-Linfoma de Células T do Adulto/patologia , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
9.
Pathol Int ; 70(5): 280-286, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32052529

RESUMO

Primary splenic low-grade B-cell lymphoma of the red pulp comprises hairy cell leukemia (HCL) and splenic B-cell lymphoma/leukemia, unclassifiable (SPLL-U). SPLL-U is a rare disease that includes subtypes of a hairy cell leukemia-variant (HCL-v), splenic diffuse red pulp small B-cell lymphoma (SDRPL) and other types that are known as narrow sense SPLL-U (SPLL-U-NS). Notably, limited information is available regarding the BRAF mutation (V600E) and cyclin D3 expression in subtypes of SPLL-U. Therefore, we performed a pathological analysis of the BRAF mutation (V600E) and characterized pathological features of SPLL-U. We reviewed the pathological findings of 12 SPLL-U cases. The 12 cases considered included two cases of HCL-v, six cases of SPLL-U-NS and four undetermined cases. The BRAF mutation (V600E) was detected in three cases, which were all SPLL-U-NS. Cases with the BRAF mutation (V600E) have increased levels of CD103 expression and decreased cyclin D3 and cyclin D1 expression compared with cases that lacked the BRAF mutation. These findings suggest that the BRAF mutation might play a significant role in SPLL-U. Therefore, the significance of the BRAF mutation should be evaluated via genomic or transcriptional analyses of a large cohort of SPLL-U patients.


Assuntos
Linfoma de Células B/genética , Linfoma de Células B/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação
10.
J Clin Exp Hematop ; 59(1): 22-28, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30918141

RESUMO

Hypercalcemia due to malignant tumors including malignant lymphomas is relatively common. Among cancer patients with hypercalcemia, humoral hypercalcemia of malignancy is the most common and accounts for about 80% of all cases with hypercalcemia. 1,25-dihydroxyvitamin D3(1,25(OH)2D3)-mediated hypercalcemia is relatively rare. Although malignant lymphoma has been also reported to cause 1,25(OH)2D3-mediated hypercalcemia, it is not known whether there is any association between 1,25(OH)2D3-mediated hypercalcemia and any specific histological type of malignant lymphoma. We herein report a case of an anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK) -negative with 1,25(OH)2D3-mediated hypercalcemia, which has never been previously reported. An 80-year-old Japanese man was admitted to our department due to acute exacerbation of hypercalcemia. He was diagnosed with ALCL, ALK-negative. Serum 1,25(OH)2D3 level was high and seemed to be associated with the lymphoma because the serum calcium and 1,25(OH)2D3 levels improved in response to chemotherapy. Histological findings showed that many CD68 positive macrophages were observed in the microenvironment of tumor cells. Lymphoma cells or tumor microenvironmental cells may produce 1,25(OH)2D3 because several previous reports showed the source of 1,25(OH)2D3 can be either lymphoma or tumor microenvironmental cells. Moreover, because 1,25(OH)2D3-mediated hypercalcemia has been reported regardless of the specific histological type of lymphoma, tumor microenvironmental cells may be involved in this condition. However, we could not identify the source of 1,25(OH)2D3 in this case. The association between 1,25(OH)2D3 production and prognosis in malignant lymphomas is yet unknown; further studies are needed to elucidate the clinical characteristics of malignant lymphoma with 1,25(OH)2D3-mediated hypercalcemia.


Assuntos
Hipercalcemia/etiologia , Linfoma Anaplásico de Células Grandes/complicações , Vitamina D/análogos & derivados , Idoso de 80 Anos ou mais , Fluordesoxiglucose F18 , Humanos , Linfoma Anaplásico de Células Grandes/diagnóstico , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Vitamina D/sangue
11.
Haematologica ; 104(8): 1626-1632, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30630986

RESUMO

Attenuated human leukocyte antigen (HLA) class I expression is implicated as a major immune escape mechanism in several types of tumor. We previously reported that HLA class I/ß2 microglobulin and programmed death ligand-1 expression are prognostic factors in adult T-cell leukemia/lymphoma. A recent report suggested that HLA class II expression is also an important prognostic factor for the clinical outcome of programmed death-1 blockade therapy in recurrent/refractory Hodgkin lymphoma. This prompted us to evaluate HLA class II expression in adult T-cell leukemia/lymphoma and to compare the findings with the patients' clinicopathological features. Of the 132 biopsy specimens examined from newly diagnosed patients, lymphoma cells were positive for HLA class II expression in 44 patients (33.3%), whereas programmed death ligand-1 expression was observed on neoplastic cells from nine patients (6.9%) and on stromal cells in the tumor microenvironment in 83 cases (62.9%). HLA class II-positive cases showed a significantly better overall survival compared to the HLA class II-negative cases (P<0.0001). Patients positive for HLA class II and programmed death ligand-1 microenvironmental expression had significantly better prognosis than the other groups (P<0.0001). HLA class II-positive and HLA class II-negative groups also showed a significant difference in complete remission rate (P=0.0421), HLA class I/ß2 microglobulin expression (P=0.0165), and the number of programmed death-1-positive tumor infiltrating cells (P=0.0020). HLA class II expression was a prognostic factor for overall survival both in univariate and multivariate analyses (P<0.0001 and P=0.0007, respectively). Our study reveals that HLA class II is a novel prognostic factor in adult T-cell leukemia/lymphoma.


Assuntos
Expressão Gênica , Antígenos de Histocompatibilidade Classe II/genética , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores , Biomarcadores Tumorais/metabolismo , Terapia Combinada , Feminino , Humanos , Imuno-Histoquímica , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico
12.
Cogn Neurosci ; 10(1): 30-43, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29327652

RESUMO

The objective of the present study was to clarify the variation in and properties of mental images and policies used to regulate specific image selection when learning to control a brain-computer interface. Healthy volunteers performed a reaching task with a virtually generated monkey tail-like object on a computer monitor by regulating event-related desynchronization (ERD) on the buttock area of the sensorimotor cortex as recorded by electroencephalogram (EEG). Participants were instructed to find a free image by which the tail was well controlled. Seven participants frequently returned to specific images that were mostly unrelated to a tail, and returned to these images on the last day of training. The ERD levels were greater during use of those selected images versus when selected images were not employed. Our results suggest that individuals adopted a mental strategy where they imagine what would reduce the prediction error between the predicted and actual BCI actions.


Assuntos
Interfaces Cérebro-Computador , Imaginação/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Movimento/fisiologia , Adulto Jovem
13.
Intern Med ; 58(4): 575-580, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30210134

RESUMO

A 61-year-old woman exhibited right inguinal lymphadenopathy and right lower limb edema approximately 1 month prior to hospitalization. She was diagnosed with high grade B-cell lymphoma, and a lymph node biopsy and fluorescence in situ hybridization indicated MYC, BCL2, and BCL6 rearrangements (triple-hit lymphoma). She had progressive disease that was CD20-negative after two courses of rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high-dose cytarabine (R-CODOX-M/IVAC) therapy. Subsequent etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (EPOCH) therapy was not effective. However, after two cycles of gemcitabine, dexamethasone, and cisplatin (GDP) therapy, she achieved a complete response and was able to undergo autologous peripheral blood stem cell transplantation. GDP therapy may be effective as salvage therapy for chemotherapy-resistant triple-hit lymphoma.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Proteínas de Ligação a DNA/genética , Desoxicitidina/análogos & derivados , Dexametasona/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/genética , Desoxicitidina/uso terapêutico , Feminino , Rearranjo Gênico , Humanos , Linfoma de Células B/patologia , Pessoa de Meia-Idade , Terapia de Salvação , Resultado do Tratamento , Gencitabina
14.
Hematol Oncol ; 37(2): 212-214, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30394560
15.
J Clin Exp Hematop ; 58(4): 161-165, 2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30305475

RESUMO

Erdheim-Chester disease (ECD), a rare form of non-Langerhans cell histiocytosis, is characterized by the infiltration of foamy CD68+ and CD1a- histiocytes into multiple organ systems. Central nervous system (CNS) involvement has recently been reported to be a poor prognostic factor when treating ECD with interferon alpha. We report the case of a 66-year-old Japanese patient with ECD involving the CNS who harbored the BRAF V600E mutation and also concomitantly developed polycythemia vera with the JAK2 V617F mutation. We confirmed 2-chlorodeoxyadenosine (cladribine) therapy to be effective for the patient in this case.


Assuntos
Doenças do Sistema Nervoso Central , Cladribina/administração & dosagem , Doença de Erdheim-Chester , Janus Quinase 2 , Mutação de Sentido Incorreto , Policitemia Vera , Proteínas Proto-Oncogênicas B-raf , Idoso , Substituição de Aminoácidos , Doenças do Sistema Nervoso Central/diagnóstico por imagem , Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/enzimologia , Doenças do Sistema Nervoso Central/genética , Doença de Erdheim-Chester/diagnóstico por imagem , Doença de Erdheim-Chester/tratamento farmacológico , Doença de Erdheim-Chester/enzimologia , Doença de Erdheim-Chester/genética , Humanos , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Masculino , Policitemia Vera/diagnóstico por imagem , Policitemia Vera/tratamento farmacológico , Policitemia Vera/enzimologia , Policitemia Vera/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo
16.
J Clin Exp Hematop ; 58(3): 136-140, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30012921

RESUMO

Ibrutinib (IBR) covalently binds to the active site of Bruton's tyrosine kinase (BTK) and is used for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL). Approximately 5-10% of CLL is complicated by autoimmune cytopenia (AIC), such as autoimmune hemolytic anemia (AIHA). Several cases of AIC have reportedly demonstrated improvement during IBR treatment. However, in our case, the patient developed AIHA during oral IBR treatment. As AIHA is exacerbated by the increased number of CLL cells in the peripheral blood, it may have developed because of disease progression rather than IBR use. This phenomenon may also be attributed to the production of autoantibodies due to increased number of CD5+ B cells. In this case, withdrawal of IBR and administration of rituximab improved hemolysis. If AIHA develops during treatment, its etiology must be examined to confirm the effects of treatment.


Assuntos
Anemia Hemolítica Autoimune/induzido quimicamente , Anemia Hemolítica Autoimune/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Rituximab/administração & dosagem , Adenina/análogos & derivados , Idoso , Anemia Hemolítica Autoimune/sangue , Autoanticorpos/sangue , Humanos , Leucemia Linfocítica Crônica de Células B/sangue , Masculino , Piperidinas , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem
17.
Hematol Oncol ; 36(3): 591-599, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29602174

RESUMO

Myeloid sarcoma (MS) is a rare condition and is an extramedullary tumour of immature myeloid cells. It is now known that the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway suppresses the host antitumor responses and that these products are expressed on both tumour cells and tumour-infiltrating cells in various malignancies. However, little is known about the significance of PD-1/PD-L1 expression on tumour cells and tumour microenvironmental cells in MS. To investigate the clinicopathological significance of PD-1/PD-L1 expression in MS, we analyzed 98 patients by immunohistochemistry. Of these, 10.2% of cases had neoplastic tumour cells positive for PD-L1 (nPD-L1+ ). However, the rate of nPD-L1+ was <5% (range: 0.27 to 2.97%). On the other hand, PD-L1 expression on 1 or more of stromal cells in the tumour microenvironment (miPD-L1+ ) was observed in 37.8% of cases. Because all nPD-L1+ cases expressed PD-1 on less than 5% of tumour cells, we compared the miPD-L1+ and miPD-L1- groups. There was a correlation between miPD-L1+ status and the number of PD-1-expressing tumour -infiltrating lymphocytes (PD-1+ TILs; P = .0229). miPD-L1+ was found to be associated with poorer overall survival and progression-free survival (P = .00392, P = .00261, respectively). Multivariate analysis also confirmed miPD-L1+ to be an independent poor prognostic factor. In conclusion, our study indicated that the immunotherapy blocking the PD-1/PD-L1 pathway may improve the clinical outcome of MS.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Sarcoma Mieloide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Sarcoma Mieloide/imunologia , Sarcoma Mieloide/metabolismo , Taxa de Sobrevida , Microambiente Tumoral/imunologia , Adulto Jovem
18.
Haematologica ; 103(6): 1018-1028, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29242302

RESUMO

The characteristics of adult patients with chronic active Epstein-Barr virus infection are poorly recognized, hindering early diagnosis and an improved prognosis. We studied 54 patients with adult-onset chronic active Epstein-Barr virus infection diagnosed between 2005 and 2015. Adult onset was defined as an estimated age of onset of 15 years or older. To characterize the clinical features of these adults, we compared them to those of 75 pediatric cases (estimated age of onset <15 years). We compared the prognosis of adult-onset chronic active Epstein-Barr virus infection with that of patients with nasal-type (n=37) and non-nasal-type (n=45) extranodal NK/T-cell lymphoma. The median estimated age of onset of these lymphomas was 39 years (range, 16-86 years). Compared to patients with pediatric-onset disease, those in whom the chronic active Epstein-Barr virus infection developed in adulthood had a significantly decreased incidence of fever (P=0.005), but greater frequency of skin lesions (P<0.001). Moreover, hypersensitivity to mosquito bites and the occurrence of hydroa vacciniforme were less frequent in patients with adult-onset disease (P<0.001 and P=0.0238, respectively). Thrombocytopenia, high Epstein-Barr virus nuclear antigen antibody titer, and the presence of hemophagocytic syndrome were associated with a poor prognosis (P=0.0087, P=0.0236, and P=0.0149, respectively). Allogeneic hematopoietic stem cell transplantation may improve survival (P=0.0289). Compared to pediatric-onset chronic active Epstein-Barr virus infection and extranodal NK/T-cell lymphoma, adult-onset chronic active Epstein-Barr virus infection had a poorer prognosis (P<0.001 and P=0.0484, respectively). Chronic active Epstein-Barr virus infection can develop in a wide age range, with clinical differences between adult-onset and pediatric-onset disease. Adult-onset chronic active Epstein-Barr virus infection is a disease with a poor prognosis. Further research will be needed.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/fisiologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Células T Matadoras Naturais/metabolismo , Células T Matadoras Naturais/virologia , Adolescente , Adulto , Fatores Etários , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Biópsia , Feminino , Humanos , Transtornos Linfoproliferativos/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Avaliação de Sintomas , Carga Viral , Adulto Jovem
19.
Hematol Oncol ; 36(1): 166-173, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29052238

RESUMO

Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is a subtype of non-Hodgkin lymphoma with a poor prognosis. Although first-line treatments for patients with localized ENKTL have been established, there is no gold standard treatment for patients with advanced ENKTL and refractory and/or relapsed disease. Anti-CD30 antibody-based therapy, including brentuximab vedotin (BV), has been shown to target malignant lymphomas with CD30 expression. In particular, this therapeutic agent has recently been suggested to be effective for Hodgkin lymphoma and mature T-cell lymphoma. However, the efficacy of BV toward ENKTL has not yet been established. Therefore, we investigated the expression of CD30 in a large cohort to evaluate BV as a potential treatment for ENKTL. In this study, 97 Japanese patients with newly diagnosed ENKTL between January 2007 and December 2015 were enrolled. Flow cytometry and immunohistochemistry were performed for the evaluation of CD30 expression. If the cut-off value of CD30 expression is 1% or more, there were 55 positive cases (56.5%). According to the localization of lesion, the frequency of CD30 expression was significantly higher in the non-nasal type than in the nasal type (P = .0394). No differences were observed in almost all clinical characteristics between CD30-positive cases and CD30-negative cases. In addition, the expression of CD30 was not a prognostic factor for either overall survival or progression-free survival. In conclusion, frequent expression of CD30 in ENKTL suggests anti-CD30 antibody-based therapy may be an effective treatment.


Assuntos
Antígeno Ki-1/metabolismo , Linfoma de Células T Periférico/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Linfoma de Células T Periférico/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
20.
Rinsho Ketsueki ; 58(8): 905-911, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-28883272

RESUMO

We retrospectively analyzed clinical and pathological features, treatments, and prognoses in 28 patients with newly diagnosed peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in Niigata University Medical and Dental Hospital. Of them, 16 were males and 12 were females, and their median age was 62.5 (range, 26-88) years. The International Prognostic Index was high-intermediate/high in 68% of patients. Twelve patients were treated with CHOP/THP-COP and nine with third-generation chemotherapy regimens. At a median follow-up period of 30 (range: 1-164) months, the 2-year overall survival and progression-free survival rates were 61% and 44%, respectively. Further investigation of novel agents for treating PTCL-NOS is warranted.


Assuntos
Linfoma de Células T Periférico/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Seguimentos , Humanos , Linfoma de Células T Periférico/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
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