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1.
Rare Dis ; 4(1): e1165909, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27274438

RESUMO

OBJECTIVE: Malignant pleural mesothelioma (MPM) is a rare and aggressive, treatment-resistant cancer. Pemetrexed, an inhibitor of thymidylate synthase (TS), is used worldwide for MPM as a first-line chemotherapy regimen. However, there is little consensus for a second-line chemotherapy. S-1, a highly effective dihydropyrimidine dehydrogenase (DPD)-inhibitory fluoropyrimidine, mainly acts via a TS inhibitory mechanism similar to pemetrexed. Orotate phosphoribosyltransferase (OPRT) is a key enzyme related to the first step activation of 5-fluorouracil (5-FU) for inhibiting RNA synthesis. We investigated 5-FU related-metabolism proteins, especially focusing on OPRT expression, in MPM Methods and Patients: Fifteen MPM patients who were diagnosed between July 2004 and December 2013 were enrolled. We examined the protein levels of 5-FU metabolism-related enzymes (TS, DPD, OPRT, and thymidine phosphorylase [TP]) in 14 cases RESULTS: High TS, DPD, OPRT, and TP expressions were seen in 28.6%, 71.4%, 85.7%, and 35.7% of patients, respectively. We found that OPRT expression was extremely high in MPM tissue. We experienced one remarkable case of highly effective S-1 combined therapy for pemetrexed refractory MPM. This case also showed high OPRT protein expression Conclusion: The present study suggests that OPRT expression is high in MPM tumors. Although pemetrexed is mainly used for MPM chemotherapy as a TS inhibitor, S-1 has potential as an anticancer drug not only as a TS inhibitor but also inhibiting RNA synthesis through the OPRT pathway. This is the first report investigating OPRT protein expressions in MPM.

2.
Intern Med ; 55(4): 399-403, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26875967

RESUMO

Gamma heavy chain disease (gHCD) is a rare lymphoproliferative disorder characterized by the production of a truncated immunoglobulin heavy chain. Although some cases of gHCD are concurrent with other lymphoid neoplasms, few have been reported. We herein present the case of a 73-year-old woman with gHCD and T-cell large granular lymphocytic leukemia. A multiparameter flow cytometry analysis revealed neoplastic cells that were positive for CD28, a marker of T-cell activation, the anti-apoptotic antigen of neoplastic plasma cells, CD38 and CD45. The results of this multiparameter flow cytometry analysis may contribute to furthering the understanding of the clinicopathological features of gHCD.


Assuntos
Anemia/imunologia , Fadiga/imunologia , Doença das Cadeias Pesadas/patologia , Cadeias gama de Imunoglobulina/metabolismo , Leucemia Linfocítica Granular Grande/patologia , Linfócitos/metabolismo , Idoso , Anemia/etiologia , Análise Citogenética , Fadiga/etiologia , Feminino , Citometria de Fluxo , Doença das Cadeias Pesadas/complicações , Doença das Cadeias Pesadas/imunologia , Humanos , Cadeias Pesadas de Imunoglobulinas , Cadeias gama de Imunoglobulina/sangue , Leucemia Linfocítica Granular Grande/complicações , Leucemia Linfocítica Granular Grande/imunologia
3.
Int J Hematol ; 99(3): 288-95, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24496825

RESUMO

Recent studies have suggested that c-Myc over-expression may be a factor indicating poor prognosis in multiple myeloma (MM), although c-Myc gene-related abnormalities, including translocation and gene amplification, have not been fully investigated in the novel agent era. Additional chromosome 8 may be considered as aggressive disease in the 1990s. To clarify the impact of these aberrations, we retrospectively analyzed newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM) with bortezomib and dexamethasone induction therapy. In the present study, the high-risk group was defined as having at least one of the following present: non-hyperdiploidy, IgH/FGFR3, and del p53. Forty NDMM cases were analyzed. At the median follow-up duration of 14.1 months, 14 RRMM were recognized. The proportions of patients in the high-risk, c-Myc gene-related aberrations, and additional chromosome 8 groups at diagnosis were 45.5, 22.5, and 10 %, respectively. The proportions of patients who developed RRMM in the high-risk, c-Myc gene-related aberrations, and additional chromosome 8 groups were 41.7, 77.7, and 50 %, respectively. Furthermore, patients with c-Myc gene-related abnormalities tended to exhibit inferior progression-free survival (PFS), and those with c-Myc gene-related abnormalities and/or additional chromosome 8 showed statistically shorter PFS. Therefore, c-Myc gene-related abnormalities and additional chromosome 8 may be related to a poorer prognosis.


Assuntos
Aberrações Cromossômicas , Expressão Gênica , Genes myc/genética , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácidos Borônicos , Bortezomib , Cromossomos Humanos Par 8/genética , Intervalo Livre de Doença , Feminino , Seguimentos , Amplificação de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Prognóstico , Pirazinas , Recidiva , Estudos Retrospectivos
4.
Intern Med ; 52(24): 2801-4, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24334589

RESUMO

Extramedullary hematopoietic effusion (EHE) is recognized to be an unusual phenomenon accompanied by hematologic disorders. Only a few reports are available of EHE occurring in patients with lymphoma. We herein report the case of a 54-year-old man with follicular lymphoma. Bone marrow aspirates and biopsied specimens showed diffuse invasion of small cleaved atypical lymphoid cells that were positive for CD10, 20, bcl2, immunoglobulin lambda and Bcl-2-IgH rearrangement. The pleural effusion aspirates and a biopsied specimen obtained via thoracoscopy revealed megakaryocytes and immature myeloid cells in addition to lymphoma cells. To the best of our knowledge, this is the first report of EHE accompanied by lymphoma according to the World Health Organization classification.


Assuntos
Hematopoese Extramedular , Linfoma Folicular/complicações , Derrame Pleural/complicações , Antígenos CD20/sangue , Hematopoese Extramedular/fisiologia , Humanos , Cadeias Pesadas de Imunoglobulinas/sangue , Cadeias lambda de Imunoglobulina/sangue , Linfoma Folicular/sangue , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Neprilisina/sangue , Derrame Pleural/sangue , Derrame Pleural/patologia , Proteína bcl-X/sangue
5.
Intern Med ; 50(21): 2653-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22041375

RESUMO

Immunoglobulin D (IgD) myeloma is a rare subtype and it is widely accepted as an aggressive disease. Here, we report a 66-year-old woman with IgD myeloma who had anemia, lumbago, multiple osteolytic lesions and hypercalcemia. The patient refused a blood transfusion because of her beliefs, so we administered bortezomib and dexamethasone (BD) after high-dose dexamethasone therapy. Marked improvement of anemia and elevated serum alkaline phosphatase levels was recognized. After 5 cycles of BD therapy, the patient achieved a stringent complete response according to International Myeloma Working Group Response Criteria. BD therapy might be a feasible and useful treatment option for IgD myeloma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Imunoglobulina D/biossíntese , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Idoso , Ácidos Borônicos/administração & dosagem , Bortezomib , Dexametasona/administração & dosagem , Feminino , Humanos , Mieloma Múltiplo/imunologia , Pirazinas/administração & dosagem , Resultado do Tratamento
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