Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
J Clin Med ; 13(13)2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38999437

RESUMO

Background: Aggressive mature T-cell lymphoma (TCL) is a disease that carries a poor prognosis. Methods: We analyzed the expression of 22 tumor cell functional proteins in 16 randomly selected patients with TCL. Immunohistochemistry was performed in paraffin-embedded tumor tissue sections to determine the protein expression statuses in tumor cells. Results: Glucose-regulated protein 94 (GRP94), a protein that serves as a pro-survival component under endoplasmic reticulum (ER) stress in the tumor microenvironment, was significantly associated with a shortened survival. Furthermore, significant differences were observed when GRP94 was combined with six other factors. The six factors were (1) programmed cell death-ligand 1 (PD-L1); (2) programmed cell death 1 (PD-1); (3) aldo-keto reductase family 1 member C3 (AKR1C3); (4) P53, a tumor suppressor; (5) glucose-regulated protein 78 (GRP78), an ER stress protein; and (6) thymidine phosphorylase (TP). Based on the combination of GRP94 and the six other factors expressed in the tumors, we propose a new prognostic classification system for TCL (TCL Urayasu classification). Group 1 (relatively good prognosis): GRP94-negative (n = 6; median OS, 88 months; p < 0.01); Group 2 (poor prognosis): GRP94-positive, plus expression of two of the six factors mentioned above (n = 5; median OS, 25 months; p > 0.05); and Group 3 (very poor prognosis): GRP94-positive, plus expression of at least three of the six factors mentioned above (n = 5; median OS, 10 months; p < 0.01). Conclusions: Thus, the TCL Urayasu prognostic classification may be a simple, useful, and innovative classification that also explains the mechanism of resistance to treatment for each functional protein. If validated in a larger number of patients, the TCL Urayasu classification will enable a targeted treatment using selected inhibitors acting on the abnormal protein found in each patient.

2.
J Clin Med ; 12(19)2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37834968

RESUMO

We conducted a retrospective analysis of GRP94 immunohistochemical (IHC) staining, an ER stress protein, on large B-cell lymphoma (LBCL) cells, intracellular p53, and 15 factors involved in the metabolism of the CHOP regimen: AKR1C3 (HO metabolism), CYP3A4 (CHOP metabolism), and HO efflux pumps (MDR1 and MRP1). The study subjects were 42 patients with LBCL at our hospital. The IHC staining used antibodies against the 17 factors. The odds ratios by logistic regression analysis used a dichotomous variable of CR and non-CR/relapse were statistically significant for MDR1, MRP1, and AKR1C3. The overall survival (OS) after R-CHOP was compared by the log-rank test. The four groups showed that Very good (5-year OS, 100%) consisted of four patients who showed negative IHC staining for both GRP94 and CYP3A4. Very poor (1-year OS, 0%) consisted of three patients who showed positive results in IHC for both GRP94 and CYP3A4. The remaining 35 patients comprised two subgroups: Good (5-year OS 60-80%): 15 patients who showed negative staining for both MDR1 and AKR1C3 and Poor (5-year OS, 10-20%): 20 patients who showed positive staining for either MDR, AKR1C3, MRP1, or p53. The Histological Prognostic Index (HPI) (the four groups: Very poor, Poor, Good, and Very good) is a breakthrough method for stratifying patients based on the factors involved in the development of treatment resistance.

3.
J Clin Exp Hematop ; 63(2): 83-89, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37121717

RESUMO

We conducted this study with the objective of elucidating the mechanism of development of fibrosis in hematologic neoplasms and develop treatments for these patients. Among the suggested mechanisms of development of fibrosis is cases of hematologic neoplasms is the production of TGF-beta1 (transforming growth factor-beta-1) and TNF-alpha1 (tumor necrotizing factor-alpha-1) by the tumor cells, both of which are fibrosis-stimulating cytokines that act on fibroblasts to promote fibrosis. However, there are few reports based on human clinical pathology studies. We conducted an immunohistochemical study on paraffin-embedded formalin-fixed specimens obtained from 104 patients with various pathologic conditions (acute leukemia, malignant lymphoma, inflammation, cancer, etc.). The association of tissue fibrosis with positive immunohistochemistry for TGF- beta1 and/or TNF-alpha1, TGF-beta1 was found to be strongly associated with tissue fibrosis, and in cases with positive immunohistochemistry for TGF-beta1, the odds ratio for fibrosis was 12.8, which was significantly high. Combined positivity for TGF-beta1 and TNF-alpha1 was also associated with a significant odds ratio for fibrosis of 3.4, suggesting that TGF-beta1 expression is an important prerequisite. TGF-beta1 has been suggested as playing a relatively important role in tissue fibrosis. Future clinical application of these cytokines for both diagnosis and treatment is expected.


Assuntos
Neoplasias Hematológicas , Fator de Crescimento Transformador beta1 , Humanos , Fator de Crescimento Transformador beta/metabolismo , Citocinas , Fibrose
4.
J Clin Exp Hematop ; 63(1): 32-36, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36990774

RESUMO

TAFRO syndrome is a rare systemic inflammatory disease characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. We encountered a case of calreticulin mutation-positive essential thrombocythemia (ET) with TAFRO syndrome-like features, followed by a rapid fatal course. The patient had been on anagrelide therapy for approximately three years for management of ET; however, she suddenly stopped going for follow-up and discontinued the medicine for a year. She presented with fever and hypotension, suggestive of septic shock, and was transferred to our hospital. The platelet count at the time of admission to another hospital was 50 × 104 / µL; however, it decreased to 25 × 104 / µL upon transfer to our hospital and further decreased to 5 × 104 / µL on the day of her death. In addition, the patient showed remarkable systemic edema and progression of organomegaly. Her condition suddenly worsened and led to her death on the 7th day of hospitalization. Postmortem, serum and pleural effusion interleukin (IL)-6 and vascular endothelial growth factor (VEGF) levels were significantly increased. Consequently, a diagnosis of TAFRO syndrome, since she met the diagnostic criteria for clinical findings and had high cytokine concentrations. Dysregulation of cytokine networks has also been reported in ET. Therefore, concurrent ET and TAFRO syndrome may have further triggered cytokine storms and contributed to the aggravation of the disease on development of TAFRO syndrome. To the best of our knowledge, this is the first report of complications seen in a patient with TAFRO syndrome due to ET.


Assuntos
Hiperplasia do Linfonodo Gigante , Trombocitemia Essencial , Feminino , Humanos , Trombocitemia Essencial/complicações , Trombocitemia Essencial/diagnóstico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Hiperplasia do Linfonodo Gigante/diagnóstico , Edema/complicações , Edema/diagnóstico , Edema/tratamento farmacológico , Febre/tratamento farmacológico , Citocinas
5.
Am J Hosp Palliat Care ; 40(8): 812-819, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36413462

RESUMO

BACKGROUND: Clinicians can appropriately terminate treatment or reduce treatment intensity by determining prognostic factors of end-of-life chemotherapy. In particular, it provides important information for patients with hematological malignancies who receive chemotherapy until near-the-end of life compared with patients with solid tumors. This study aimed to clarify whether existing prognostic tools are associated with the survival in patients with end-of-life hematological malignancies who received chemotherapy. METHODS: We retrospectively reviewed the records of 247 patients diagnosed with hematological malignancies and died at our university hospital hematology ward between May 2015 and May 2021. We performed multivariate analysis in 82 (33.2%) patients who received end-of-life chemotherapy using the Palliative Prognostic Index (PPI) and inflammation-based prognostic models, such as the Glasgow Prognostic Score (GPS), Prognostic Nutritional Index (PNI), and Controlling Nutrition Status (CONUT). RESULTS: On comparing 82 patients who received end-of-life chemotherapy with 165 patients who did not, the proportion of patients with PPI group A, GPS score = 0, and CONUT normal/mild was significantly higher among patients who received chemotherapy. In multivariate analysis, we identified PPI groups B (2.0 < PPI ≤ 4.0) and C (PPI > 4.0) [hazard ratio (HR) 2.1290, 95% CI 1.1830-3.828, P = .01166, respectively] and age ≥ 65 years (HR 2.0170, 95% CI 1.1280-3.607, P = .01805) were associated with overall survival. CONCLUSION: PPI use and age were independent associating factors for patients with hematological malignancies receiving end-of-life chemotherapy. PPI, a popular prognostic tool may be helpful for patients and hematologists to make decisions about end-of-life care.


Assuntos
Neoplasias Hematológicas , Estado Nutricional , Humanos , Idoso , Estudos Retrospectivos , Prognóstico , Neoplasias Hematológicas/tratamento farmacológico , Morte
6.
Intern Med ; 62(3): 459-463, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35793963

RESUMO

Many patients with primary vitreoretinal lymphoma (PVRL) exhibit central nervous system (CNS) involvement either at the diagnosis or during follow-up. The prognosis in the patients of PVRL with relapsed or refractory CNS remains extremely poor. We herein report a patient with refractory PVRL who had recurrence in the spinal cord despite receiving high-dose methotrexate-based chemotherapy and whole-brain radiotherapy. The patient surprisingly responded to tirabrutinib temporarily. We believe that this case suggests the utility of this new target therapy.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma , Neoplasias da Retina , Humanos , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/patologia , Neoplasias da Retina/terapia , Corpo Vítreo/patologia , Neoplasias do Sistema Nervoso Central/patologia , Medula Espinal/patologia , Linfoma/diagnóstico
7.
JCO Oncol Pract ; 18(1): e108-e116, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34357786

RESUMO

PURPOSE: Uncertainty of prognosis is one reason patients with hematologic malignancies receive aggressive therapy near end of life more often than those with advanced solid tumors. It is unknown whether end-of-life prognosis prediction models are useful for patients with hematologic malignancies, especially hospitalized patients receiving chemotherapy, because most prognostic models were developed for patients with solid tumors. The purpose of this study was to evaluate the prognostic accuracy of the Palliative Prognostic Index (PPI) for end-of-life patients with advanced hematologic malignancies. METHODS: We retrospectively reviewed the records of 143 patients who became resistant to standard chemotherapy and died of disease progression in our university hospital hematology ward between May 2015 and November 2019. Patients were classified according to PPI scores (groups: A, PPI ≤ 2.0; B, 2.0 < PPI ≤ 4.0; and C, PPI > 4.0) based on their clinical charts at admission. The median overall survival for each patient (95% confidence interval) was calculated using the Kaplan-Meier method. Log-rank tests were used to determine significant differences between survival curves. RESULTS: Median patient age was 76 years (range: 39-92 years), and 59% were men. Median overall survival times in the PPI groups A, B, and C were 58 days, 36 days, and 10 days, respectively. Statistically significant differences in survival time were observed between the groups (P < .01); prediction accuracy was similar to that for patients with different diagnoses. CONCLUSION: The usefulness of PPI was validated for near-end-of-life hospitalized patients with hematologic malignancies.


Assuntos
Neoplasias Hematológicas , Adulto , Idoso , Idoso de 80 Anos ou mais , Morte , Neoplasias Hematológicas/tratamento farmacológico , Hospitais , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA