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1.
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
2.
Yonsei Med J ; 61(10): 895-900, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32975065

RESUMO

The purpose of this study was to evaluate the diagnostic performance of magnetic resonance (MR) radiomics-based machine learning algorithms in differentiating squamous cell carcinoma (SCC) from lymphoma in the oropharynx. MR images from 87 patients with oropharyngeal SCC (n=68) and lymphoma (n=19) were reviewed retrospectively. Tumors were semi-automatically segmented on contrast-enhanced T1-weighted images registered to T2-weighted images, and radiomic features (n=202) were extracted from contrast-enhanced T1- and T2-weighted images. The radiomics classifier was built using elastic-net regularized generalized linear model analyses with nested five-fold cross-validation. The diagnostic abilities of the radiomics classifier and visual assessment by two head and neck radiologists were evaluated using receiver operating characteristic (ROC) analyses for distinguishing SCC from lymphoma. Nineteen radiomics features were selected at least twice during the five-fold cross-validation. The mean area under the ROC curve (AUC) of the radiomics classifier was 0.750 [95% confidence interval (CI), 0.613-0.887], with a sensitivity of 84.2%, specificity of 60.3%, and an accuracy of 65.5%. Two human readers yielded AUCs of 0.613 (95% CI, 0.467-0.759) and 0.663 (95% CI, 0.531-0.795), respectively. The radiomics-based machine learning model can be useful for differentiating SCC from lymphoma of the oropharynx.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Linfoma/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Neoplasias Orofaríngeas/diagnóstico por imagem , Orofaringe/diagnóstico por imagem , Algoritmos , Biópsia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Aumento da Imagem/métodos , Linfoma/patologia , Aprendizado de Máquina , Neoplasias Orofaríngeas/patologia , Orofaringe/patologia , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento
3.
Mutat Res ; 856-857: 503230, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32928375

RESUMO

This work investigates a completely novel and experimental concept of exposing L5178Y cells at the air-agar-interface to mainstream cigarette smoke aerosol (Kentucky reference 3R4F). This study highlights the associated challenges of combining a suspension cell line alongside an in vitro aerosol exposure system. To achieve a monolayer, cells were 'seeded' in a concentrated cell super-mix suspension onto an RPMI/agar-matrix -base. The resulting cell suspension media was adsorbed into the agar base leaving the L5178Y cells lightly suspended on the agar surface, approximating a monolayer. Cells were deemed supportable on the agar-matrix, viable and recoverable. Using Vitrocell VC 10 exposure system and the Ames 4 exposure module, L5178Y cells were successfully exposed to a dynamic cigarette smoke aerosol, recovered and assessed for mutant frequencies, using standard assay procedures. Method development included assessment of flowing air conditions, plating efficiency and recovery of L5178Y cells from the agar-matrix surface. Positive controls MMS and B[a]P were successfully incorporated into the agar-matrix and metabolic activation was achieved by S-9 incorporation into the same agar-base-matrix. B[a]P demonstrated metabolic activation and positive response, suggesting a clear cellular interaction with the agar-matrix. Whole smoke exposed cells in the presence of metabolic activation showed a clear dose response and increasing mutant frequencies, well in excess of the controls (air and incubator) and the global evaluation factor following a 2 or 3 day expression period. This experimental concept demonstrates that L5178Y cells can be exposed to cigarette smoke aerosol, using a completely novel and a previously untested approach. Although this work successfully demonstrates the approach is viable and cells can be plated and maintained on an agar-matrix, more optimisation and robustness assessment is required before it can be considered fully adapted and used alongside other whole aerosol methodologies for the assessment of cigarette smoke and other inhaled aerosols.


Assuntos
Linfoma/patologia , Testes de Mutagenicidade , Mutagênicos/toxicidade , Fumaça/efeitos adversos , Aerossóis/farmacologia , Aerossóis/toxicidade , Ágar/química , Ar , Animais , Linhagem Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sistemas Eletrônicos de Liberação de Nicotina , Humanos , Linfoma/induzido quimicamente , Camundongos , Mutagênicos/farmacologia
5.
Ideggyogy Sz ; 73(7-08): 275-285, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32750245

RESUMO

Background and aims - Description of two cases of rare intravascular large B-cell lymphoma and secondary T-cell lymphoma diagnosed postmortem, that manifested clinically as longitudinally extensive transverse myelitis (LETM). We discuss causes of diagnostic difficulties, deceptive radiological and histological investigations, and outline diagnostic procedures based on our and previously reported cases. Case reports - Our first case, a 48-year-old female was admitted to the neurological department due to paraparesis. MRI suggested LETM, but the treatments were ineffective. She died after four weeks because of pneumonia and untreatable polyserositis. Pathological examination revealed intravascular large B-cell lymphoma (IVL). Our second case, a 61-year-old man presented with headache and paraparesis. MRI showed small bitemporal lesions and lesions suggesting LETM. Diagnostic investigations were unsuccessful, including tests for possible lymphoma (CSF flow cytometry and muscle biopsy for suspected IVL). Chest CT showed focal inflammation in a small area of the lung, and adrenal adenoma. Brain biopsy sample from the affected temporal area suggested T-cell mediated lymphocytic (paraneoplastic or viral) meningoencephalitis and excluded diffuse large B-cell lymphoma. The symptoms worsened, and the patient died in the sixth week of disease. The pathological examination of the presumed adenoma in the adrenal gland, the pancreatic tail and the lung lesions revealed peripheral T-cell lymphoma, as did the brain and spinal cord lesions. Even at histological examination, the T-cell lymphoma had the misleading appearance of inflammatory condition as did the MRI. Conclusion - Lymphoma can manifest as LETM. In cases of etiologically unclear atypical LETM in patients older than 40 years, a random skin biopsy (with subcutaneous adipose tissue) from the thigh and from the abdomen is strongly recommended as soon as possible. This may detect IVL and provide the possibility of prompt chemotherapy. In case of suspicion of lymphoma, parallel examination of the CSF by flow cytometry is also recommended. If skin biopsy is negative but lymphoma suspicion remains high, biopsy from other sites (bone marrow, lymph nodes or adrenal gland lesion) or from a simultaneously existing cerebral lesion is suggested, to exclude or prove diffuse large B-cell lymphoma, IVL, or a rare T-cell lymphoma.


Assuntos
Encéfalo/patologia , Linfoma/patologia , Mielite Transversa/patologia , Biópsia , Evolução Fatal , Feminino , Cefaleia/etiologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Paraparesia/etiologia
6.
Nat Commun ; 11(1): 3858, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737343

RESUMO

Checkpoint blockade therapy has provided noteworthy benefits in multiple cancers in recent years; however, its clinical benefits remain confined to 10-40% of patients with extremely high costs. Here, we design an ultrafast, low-temperature, and universal self-assembly route to integrate immunology-associated large molecules into metal-organic-framework (MOF)-gated mesoporous silica (MS) as cancer vaccines. Core MS nanoparticles, acting as an intrinsic immunopotentiator, provide the niche, void, and space to accommodate antigens, soluble immunopotentiators, and so on, whereas the MOF gatekeeper protects the interiors from robust and off-target release. A combination of MOF-gated MS cancer vaccines with systemic programmed cell death 1 (PD-1) blockade therapy generates synergistic effects that potentiate antitumour immunity and reduce the effective dose of an anti-PD-1 antibody to as low as 1/10 of that for PD-1 blockade monotherapy in E.G7-OVA tumour-bearing mice, with eliciting the robust adaptive OVA-specific CD8+ T-cell responses, reversing the immunosuppressive pathway and inducing durable tumour suppression.


Assuntos
Anticorpos Neutralizantes/farmacologia , Vacinas Anticâncer/farmacologia , Linfoma/terapia , Estruturas Metalorgânicas/farmacologia , Nanopartículas/administração & dosagem , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Animais , Antígenos de Neoplasias/administração & dosagem , Antígenos de Neoplasias/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/química , Citotoxicidade Imunológica , Composição de Medicamentos , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Imunoterapia/métodos , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Linfoma/imunologia , Linfoma/mortalidade , Linfoma/patologia , Estruturas Metalorgânicas/síntese química , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Receptor de Morte Celular Programada 1/imunologia , Dióxido de Silício/química , Análise de Sobrevida , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Clin Nucl Med ; 45(11): 888-889, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32604124

RESUMO

Primary sacral lymphoma is an unusual bone malignant tumor that poses a diagnostic challenge. Herein, we report a rare case of primary sacral lymphoma, which was initially assessed as suspicious bone metastasis. The subsequent histology and immunohistochemistry of the sacral biopsy confirmed the diagnosis of diffuse large B-cell lymphoma.


Assuntos
Fluordesoxiglucose F18 , Linfoma/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Sacro/diagnóstico por imagem , Biópsia , Feminino , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade
9.
Ann Hematol ; 99(7): 1485-1491, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32488602

RESUMO

No agreement had been reached on the treatment of patients with pure red cell aplasia (PRCA) secondary to indolent malignancies. Data was collected from patients with acquired PRCA from May, 2014 to May, 2018 in Peking Union Medical College Hospital. Tumor-associated PRCA and primary PRCA patients were matched at a ratio of 1:2 with compatible baseline characteristics. All patients had been treated with CsA or sirolimus for at least 6 months with the efficacy and adverse events recorded. Twelve tumor-associated PRCA patients (3 thymoma, 8 lymphoproliferative disorders, and 1 smoldering multiple myeloma) with stable underling disease and 24 acquired primary PRCA patients were selected. 83.3% tumor-associated PRCA patients and 100% primary PRCA patients (P = 0.436) responded to immunosuppression therapy (IST) at a median of 2.5 and 3.5 months (P = 0.137), respectively. No different was found in side effects. The ORR at the end of a median of 21.5-month follow-up was 75% and 70.8% (P = 0.795), respectively. No tumor progression was reported except one secondary patient had lymphoma relapse after 2 years of IST and was given chemotherapy again. These results suggested IST had similar effect, safety on patients with tumor-associated, and primary PRCA patients when the tumors were stable.


Assuntos
Imunossupressão , Imunossupressores/uso terapêutico , Neoplasias/complicações , Aplasia Pura de Série Vermelha/tratamento farmacológico , Aplasia Pura de Série Vermelha/etiologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Linfoma/complicações , Linfoma/tratamento farmacológico , Linfoma/patologia , Transtornos Linfoproliferativos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Timoma/complicações , Timoma/tratamento farmacológico , Timoma/patologia , Neoplasias do Timo/complicações , Neoplasias do Timo/tratamento farmacológico , Neoplasias do Timo/patologia , Resultado do Tratamento
10.
Am J Clin Pathol ; 154(3): 394-402, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32525969

RESUMO

OBJECTIVES: A definitive diagnosis of malignancy may not be possible in pleural effusions. We report our experience with the diagnosis of suspicious for malignancy (SFM) in pleural effusion. METHODS: A search for pleural effusions diagnosed as SFM (2008-2018) was performed. Patient records and pathology reports were reviewed. Specimens were subdivided into groups depending on volume (<75, 75-400, >400 mL). Diagnoses of malignant pleural effusion (MPE) served as controls. RESULTS: We identified 90 patients, with a mean age of 60.6 years. Diagnoses included suspicious for involvement by carcinoma/adenocarcinoma in 64.4%, leukemia/lymphoma in 15.6%, melanoma in 2.2%, sarcoma in 3.3%, germ cell tumor in 1.1%, and not otherwise specified in 13.3%. Immunostains were performed in 47.8% and considered inconclusive in 24%. Average sample volume was 419 mL. There was a statistically significant difference between the SFM vs MPE groups for volumes greater than 75 mL (P = .001, χ 2 test), with SFM having increased proportion of volumes  greater than 400 mL, compared with the MPE group. There was no statistically significant difference in mean overall survival when the groups were compared (P = .49). CONCLUSIONS: Samples with low cellularity, scant cell blocks, and inconclusive immunostains may contribute to a suspicious category diagnosis in pleural effusions.


Assuntos
Adenocarcinoma/diagnóstico , Linfoma/diagnóstico , Derrame Pleural Maligno/diagnóstico , Derrame Pleural/patologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Citodiagnóstico , Feminino , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/patologia , Sensibilidade e Especificidade , Adulto Jovem
11.
Clin Nucl Med ; 45(8): e373-e375, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32558708

RESUMO

We report the case of a 23-year-old man with nodal EMH (extramedullary hematopoiesis) occurring during treatment for a stage IIA "gray-zone" lymphoma. Although it is often related to myeloproliferative bone marrow disease, benign etiologies such as lenograstim treatment after chemotherapy can also induce EMH and be responsible for false-positive F-FDG PET/CT examinations. In this respect, GLUT overexpression in hematopoietic lineages and macrophages of the inflammatory environment are responsible for increased F-FDG uptake. Histopathologic confirmation of new hypermetabolic lesions on follow-up PET/CT may be required when the new lesions do not conform with the treatment responses in the preexisting lesions.


Assuntos
Fluordesoxiglucose F18 , Hematopoese Extramedular/efeitos dos fármacos , Lenograstim/efeitos adversos , Linfoma/tratamento farmacológico , Linfoma/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Humanos , Linfoma/diagnóstico por imagem , Masculino , Estadiamento de Neoplasias , Adulto Jovem
12.
Hematol Oncol ; 38(4): 493-500, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32533716

RESUMO

The aim was to build a prognostic model to stratify patients at diagnosis into different risk categories. We investigated the prognostic value of functional PET parameters and clinical features in 64 primary breast lymphoma (PBL) patients. With a median follow-up of 60 months, 5-year progression-free survival (PFS) and overall survival (OS) was 62.5% and 73.4%. In multivariate analysis, baseline total metabolic tumor volume (TMTV0) and ß2-microglobulin remained more reliable predictors of survival than other prognostic factors. The optimal TMTV0 cut-off value was 90 cm3 . Among 29 patients with high TMTV0, 5-year PFS and OS were 44.8% and 62.1%, respectively, while 5-year PFS and OS of 35 patients with low TMTV0 were 74.3% and 85.7%, respectively. TMTV0 combined with ß2-microglobulin identified three groups with very different prognosis, including low-risk group with low TMTV0 and ß2-microglobulin≤normal (n = 30), intermediate-risk group with high TMTV0 or ß2-microglobulin>normal (n = 20), and high-risk group with high TMTV0 and ß2-microglobulin>normal (n = 14). In the three groups, 5-year PFS rates were 80%, 55% and 28.6% (P = .003), and 5-year OS rates were 90%, 65%, and 50% (P = .023) respectively. We established a new prognostic model through TMTV0 and ß2-microglobulin, and can divide PBL at diagnosis into different risk categories.


Assuntos
Neoplasias da Mama/patologia , Fluordesoxiglucose F18/metabolismo , Linfoma/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Carga Tumoral , Microglobulina beta-2/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Linfoma/diagnóstico por imagem , Linfoma/metabolismo , Linfoma/terapia , Pessoa de Meia-Idade , Prognóstico , Compostos Radiofarmacêuticos/metabolismo , Taxa de Sobrevida , Adulto Jovem
13.
Rev Assoc Med Bras (1992) ; 66(2): 210-215, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32428157

RESUMO

OBJECTIVES: Lymphomas are a heterogeneous set of malignant neoplasias of lymphoid B and NK/T mature and immature cells at various stages of differentiation. Genetic and molecular biology tools are used to appropriately classify the type and prognosis of the lymphomas, which have implications in therapeutic effectiveness. Among them, the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) oxidase (NOX5) enzymes have been explored. This study analyzed the expression of NADPH oxidase 5 in lymphoma tissue according to the degree of tumor aggressiveness. METHODS: Slides from 64 patients with lymphoma who had paraffin-embedded tissue available were reviewed by two independent, experienced pathologists. They classified tumors according to the WHO classification (2017). NOX5 expression in tissues was assessed by immunohistochemical staining using a tissue microarray. The assay was interpreted using a scoring system of 0, 1, 2, and 3, for cytoplasmic staining of NOX5 corresponding to negative, weak, intermediate, and strong staining, respectively. We compared the expression of NOX5 in patients with aggressive versus non-aggressive lymphomas. RESULTS: NOX5 expression was positive in 100% (27/27) of aggressive lymphomas and in 19% (7/37) of non-aggressive ones. The seven patients with positive expression of NOX5 presented intermediate staining (2); strong staining (3) was observed only in tissues of aggressive lymphomas, and negative and weak staining (0 and 1) were observed only in non-aggressive lymphomas. CONCLUSIONS: Aggressive lymphomas overexpress NOX5 protein. The higher NOX5 expression in aggressive lymphomas can suggest an involvement of this enzyme on the acquisition of an aggressive phenotype in lymphoid neoplasia.


Assuntos
Linfoma/patologia , NADPH Oxidase 5/análise , Regulação para Cima , Humanos , Imuno-Histoquímica , Invasividade Neoplásica , Inclusão em Parafina , Prognóstico , Estudos Retrospectivos
14.
Surg Clin North Am ; 100(3): 565-580, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32402301

RESUMO

Solid tumors of the pancreas encompass a variety of diagnoses with treatments ranging from observation to major abdominal surgery. Pancreatic ductal adenocarcinoma remains one of the most common and most lethal of these differential of diagnoses and requires a multimodality approach through a multidisciplinary team of specialists. This article reviews the classification, clinical presentation, and workup in differentiating solid tumors of the pancreas and serves as an additional tool for general surgeons faced with such a clinical finding, from a surgical oncology perspective.


Assuntos
Carcinoma Ductal Pancreático/cirurgia , Linfoma/cirurgia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Colangiopancreatografia Retrógrada Endoscópica , Diagnóstico Diferencial , Detecção Precoce de Câncer , Endossonografia , Humanos , Linfoma/diagnóstico , Linfoma/patologia , Imagem por Ressonância Magnética , Estadiamento de Neoplasias , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Pancreatectomia/métodos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Pancreatite/diagnóstico , Pancreatite/mortalidade , Pancreatite/patologia , Pancreatite/cirurgia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prognóstico , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
15.
Proc Natl Acad Sci U S A ; 117(24): 13740-13749, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32471947

RESUMO

Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of a T cell neoplasm and several inflammatory diseases. A viral gene, HTLV-1 bZIP factor (HBZ), induces pathogenic Foxp3-expressing T cells and triggers systemic inflammation and T cell lymphoma in transgenic mice, indicating its significance in HTLV-1-associated diseases. Here we show that, unexpectedly, a proinflammatory cytokine, IL-6, counteracts HBZ-mediated pathogenesis. Loss of IL-6 accelerates inflammation and lymphomagenesis in HBZ transgenic mice. IL-6 innately inhibits regulatory T cell differentiation, suggesting that IL-6 functions as a suppressor against HBZ-associated complications. HBZ up-regulates expression of the immunosuppressive cytokine IL-10. IL-10 promotes T cell proliferation only in the presence of HBZ. As a mechanism of growth promotion by IL-10, HBZ interacts with STAT1 and STAT3 and modulates the IL-10/JAK/STAT signaling pathway. These findings suggest that HTLV-1 promotes the proliferation of infected T cells by hijacking the machinery of regulatory T cell differentiation. IL-10 induced by HBZ likely suppresses the host immune response and concurrently promotes the proliferation of HTLV-1 infected T cells.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/imunologia , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Interleucina-6/imunologia , Linfoma/virologia , Proteínas dos Retroviridae/imunologia , Animais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Diferenciação Celular , Proliferação de Células , Infecções por HTLV-I/genética , Infecções por HTLV-I/patologia , Infecções por HTLV-I/virologia , Interações Hospedeiro-Patógeno , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-6/genética , Linfoma/genética , Linfoma/imunologia , Linfoma/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Retroviridae/genética , Linfócitos T Reguladores/imunologia
17.
Jpn J Clin Oncol ; 50(9): 999-1008, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32469065

RESUMO

OBJECTIVE: The optimal regimen for use of high dose-methotrexate-based chemotherapy in primary central nervous system lymphoma is still under debate. We conducted a retrospective study to evaluate the treatment outcome of a combination immunochemotherapy consisting of rituximab, methotrexate, procarbazine and vincristine followed by with or without whole brain radiotherapy and consolidation cytarabine, in comparison with high dose-methotrexate monotherapy followed by full dose whole brain radiotherapy. METHODS: Newly diagnosed primary central nervous system lymphoma patients treated with either rituximab, methotrexate, procarbazine and vincristine or high dose-methotrexate in Kyorin University Hospital were identified, and the response rates and survival were compared. Toxicities, post-treatment transition of Mini-Mental State Examination, Karnofsky performance status score, Fazekas scale and prognostic factors were analysed in the rituximab, methotrexate, procarbazine and vincristine group. RESULTS: Ninety-five patients treated with rituximab, methotrexate, procarbazine and vincristine (n = 39) or high dose-methotrexate (n = 56) were analysed. The complete response/complete response unconfirmed rate was significantly higher in the rituximab, methotrexate, procarbazine and vincristine group (74.4 vs. 15.4%, P < 0.001). Accordingly, both median progression-free survival and overall survival were significantly longer in the rituximab, methotrexate, procarbazine and vincristine group (median progression-free survival: unreached vs. 14.75 months, P < 0.001) (median overall survival: unreached vs. 63.15 months, P = 0.005). Although the rate of grade 3/4 hematologic toxicities was high both during rituximab, methotrexate, procarbazine and vincristine and consolidation cytarabine, the rate of grade 3/4 infections was low, and no treatment related deaths were observed. Deterioration in Karnofsky performance status or Mini-Mental State Examination was rare, except on disease recurrence. Although whole brain radiotherapy was associated with Fazekas scale deterioration, its association with Karnofsky performance status or Mini-Mental State Examination deterioration was not significant. CONCLUSIONS: Rituximab, methotrexate, procarbazine and vincristine was apparently promising in comparison with high dose-methotrexate monotherapy with manageable toxicity in this retrospective study, and further investigation is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma/tratamento farmacológico , Metotrexato/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias do Sistema Nervoso Central/patologia , Feminino , Humanos , Linfoma/patologia , Masculino , Metotrexato/administração & dosagem , Metotrexato/farmacologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
18.
J Cancer Res Ther ; 16(1): 60-65, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362610

RESUMO

Objective: The objective of this study is to review the multidetector computed tomography (MDCT) findings of synchronous lymphoma and other solid malignancies. Patients and Methods: This retrospective study included 18 patients confirmed with diagnosis of lymphoma and other solid malignancies. They were 8 women and 10 men (mean age, 62.5 year; range, 44-73 years). CT scanning was performed on one of the two systems: 64 MDCT in 11 patients and 6 MDCT in 7 patients. All 36 malignancies were underwent pathological evaluation. Results: All cases were confirmed pathologically. Lymphomas were Hodgkin disease ( n = 5 patients) and non-Hodgkin lymphoma ( n = 13 patients). Hepatocellular carcinoma was detected in five patients. Bronchogenic carcinoma was detected in two patients. Renal cell carcinoma was detected in two patients. Breast carcinoma was detected in two patients. Prostatic carcinoma was detected in two patients. Gastric carcinoma was detected in two patients. Endometrial carcinoma was detected in one patient. Colonic carcinoma was detected in one patient. Thyroid carcinoma was detected in one patient. Conclusions: MDCT scanning is accurately imaging modality for the evaluation of synchronous lymphoma and other solid malignancies. More reports and accumulation of such cases should help to clarify the mechanisms, contribute to a further understanding of this phenomenon, and may lead to a new treatment strategy for synchronous lymphoma and other solid malignancies.


Assuntos
Linfoma/patologia , Tomografia Computadorizada Multidetectores/métodos , Neoplasias Primárias Múltiplas/patologia , Neoplasias/patologia , Adulto , Idoso , Feminino , Humanos , Achados Incidentais , Linfoma/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Estudos Retrospectivos
19.
J Cancer Res Ther ; 16(1): 78-87, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362613

RESUMO

Aims: In the present study, the flavonoid fraction of Tabernaemontana divaricata flavonoid fraction(TdFf) leaves was investigated for its in vitro and in vivo antioxidative and antitumor activity. Subjects and Methods: The flavonoid fraction of ethyl acetate extract was assessed for their in vitro antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), superoxide radicals, ferric reducing antioxidant power (FRAP), hydrogen peroxide, hydroxyl radicals and nitric oxide and in vivo antioxidative activity by enzymic and nonenzymic antioxidants in the liver of intraperitoneally implanted Ehrlich's lymphoma (EAC) and Dalton's lymphoma ascites (DLAs) model. The in vitro cytotoxicity was assessed using trypan blue exclusion assay and in vivo antitumor activity was assessed by screening the ILS, serum liver marker enzymes and histopathology of the liver. Statistical Analysis Used: The data were expressed as the mean ± standard deviation of the means, and statistical analysis was carried out employing one-way and two-way analysis of variance using Web Agri Stat Package 2.0. Results: The dose-dependent percentage scavenging of ABTS, DPPH, FRAP, OH, superoxide radical, and nonradical NO and H2O2 by TdFf indicated their antioxidative potential. Incubation of EAC/DLA tumor cells with TdFf showed a concentration-dependent cytotoxic effect, and the extract killed 50% of EAC/DLA tumor cells at a concentration of 80 µg of TdFf. Coadministration of TdFf with EAC/DLA-induced mice showed a significant increase in the liver enzymic and nonenzymic antioxidants and significant decrease in the serum liver marker enzymes to prove the in vivo antioxidative and antitumor activity of TdFf. It was also confirmed by the histopathology of the liver. Conclusions: It may be concluded that the flavonoid fractions of Td possess considerable antioxidative and antitumorigenic activity against the tested DLA/EAC in both in vitro and in vivo system.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Ascite/tratamento farmacológico , Carcinoma de Ehrlich/tratamento farmacológico , Flavonoides/farmacologia , Linfoma/tratamento farmacológico , Tabernaemontana/química , Animais , Ascite/metabolismo , Ascite/patologia , Carcinoma de Ehrlich/metabolismo , Carcinoma de Ehrlich/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Técnicas In Vitro , Linfoma/metabolismo , Linfoma/patologia , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Extratos Vegetais/farmacologia , Folhas de Planta/química
20.
Clin Sci (Lond) ; 134(10): 1151-1166, 2020 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-32420596

RESUMO

A percentage of celiac disease (CD) patients develop refractory type-2 disease (RCD2), a condition associated with increased risk of enteropathy-associated T-cell-lymphoma (EATL) and without therapeutic option. Therefore, we profiled the miRNome in series of peripheral T-cell lymphomas (PTCLs), CD, RCD1 or 2 and in the murine interleukin-15 (IL15)-transgenic (TG) model of RCD. The transcriptome was analyzed in 18 intestinal T-cell lymphomas (ITLs). Bioinformatics pipelines provided significant microRNA (miRNA) lists and predicted targets that were confirmed in a second set of patients. Our data show that ITLs have a unique miRNA profile with respect to other PTCLs. The c-MYC regulated miR-17/92 cluster distinguishes monomorphic epitheliotropic ITL (MEITL) from EATL and prognosticates EATL outcome. These miRNAs are decreased in IL15-TG mice upon Janus kinase (JAK) inhibition. The random forest algorithm identified a signature of 38 classifier miRNAs, among which, the miR-200 and miR-192/215 families were progressively lost in RCD2 and ITL-CD, whereas miR-17/92 and C19MC miRNAs were up-regulated. Accordingly, SMAD3, MDM2, c-Myc and activated-STAT3 were increased in RCD2 and EATL tissues while JAK inhibition in IL15-TG mice restored their levels to baseline. Our data suggest that miRNAs circuit supports activation of STAT3 and c-Myc oncogenic signaling in RCD2, thus contributing to lymphomagenesis. This novel understanding might pave the way to personalized medicine approaches for RCD and EATL.


Assuntos
Carcinogênese/genética , Doença Celíaca/genética , Regulação Neoplásica da Expressão Gênica , Linfoma/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Algoritmos , Animais , Biomarcadores Tumorais/metabolismo , Feminino , Intestinos/patologia , Linfoma/patologia , Masculino , Camundongos Transgênicos , MicroRNAs/metabolismo , Modelos Biológicos , Prognóstico , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Smad3/metabolismo , Regulação para Cima/genética
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