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1.
Transfus Apher Sci ; 57(6): 790-792, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30471945

RESUMEN

Upshaw-Schulman syndrome (USS) is an inherited type of thrombotic thrombocytopenic purpura (TTP) that is extremely rare, but often diagnosed during pregnancy. Reversible cerebral vasoconstriction syndrome (RCVS) is the transient stenosis of several cerebral arteries that is frequently diagnosed post-partum. We describe a 28-year-old woman with USS complicated by RCVS after delivery that was treated by plasma exchange with a good outcome. She was referred to our hospital with thunderclap headache, anemia and thrombocytopenia that occurred immediately postpartum. She was diagnosed with TTP and multiple cerebral infarctions. Plasma exchange promptly improved her symptoms on hospital day 3. Moreover, multiple stenoses of cerebral arteries indicating RCVS were resolved. Since her sister also had an episode of thrombocytopenia during pregnancy, inherited TTP was suspected and genetic analyses confirmed USS. Pregnancy is a risk for not only TTP, but also RCVS. Endothelial damage might be an underlining cause and vasospasm after delivery is a trigger of RCVS. Plasma exchange was effective against both TTP and RCVS.


Asunto(s)
Cerebro/irrigación sanguínea , Complicaciones del Embarazo/patología , Púrpura Trombocitopénica Trombótica/diagnóstico , Vasoconstricción , Proteína ADAMTS13/genética , Adulto , Familia , Femenino , Humanos , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Mutación/genética , Embarazo , Síndrome
2.
Pathol Int ; 2018 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-29987858

RESUMEN

Although gamma heavy chain disease (γ-HCD) lesions occasionally morphologically resemble angioimmunoblastic T-cell lymphoma (AITL), no association has been described in detail due to the rarity of the disease. In this report, we present a rare manifestation of methotrexate (MTX)-associated lymphoproliferative disorders (LPDs) with AITL-like features accompanied by γ-HCD in a 75-year-old man with rheumatoid arthritis (RA). A biopsy specimen was evaluated using immunohistochemistry, clonal analyses of immunoglobulin VH and T-cell receptor γ gene rearrangements by polymerase chain reaction, and Sanger sequencing for confirmation of the structure of deleted γ-HCD clones. The histological features characterized by proliferation of CD4- and PD-1-positive medium-sized T cells and arborizing high endothelial venules together with numbers of small lymphocytes, eosinophils, plasma cells, and histiocytes in the background mimicked those of AITL, but did not completely fulfill the diagnostic criteria. Clonal analysis demonstrated that the specimen contained multiple LPDs of both B-cell and T-cell lineages. Sequence analysis confirmed the co-existence of a clone responsible for production of the abnormal heavy chain. This report provides new insights into the pathology of γ-HCD. Multiple host-derived factors (e.g., RA and/or use of MTX) may be responsible for the occurrence of LPDs of multiple lineages within a single lymph node.

3.
Br J Haematol ; 177(4): 578-587, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28340283

RESUMEN

Pulmonary hypertension (PH) is a rare, but life-threatening, adverse event in patients treated with tyrosine kinase inhibitors (TKIs), such as dasatinib, but has not been fully evaluated in patients treated with imatinib or nilotinib. We used echocardiography to noninvasively assess the incidence of PH in 105 patients with chronic myeloid leukaemia (CML) treated with imatinib (n = 37), nilotinib (n = 30) or dasatinib (n = 38). The mean triscupid regurgitation peak gradient (TRPG), which reflects pulmonary arterial pressure, was 22·7 mmHg in the imatinib group, 23·1 mmHg in the nilotinib group and 23·4 mmHg for dasatinib group. These values were not significantly different, but higher than those (19·0 mmHg) in newly diagnosed CML patients. A TRPG > 31 mmHg, marking possible PH onset, was detected in 9 of 105 patients: one (2·7%) treated with imatinib, three (10·0%) with nilotinib and five (13·2%) with dasatinib. Only three patients complained of dyspnoea, whereas the other six were asymptomatic. In addition, there was a tendency toward correlation of TRPG value and age or TKI treatment duration. These results suggested that treatment with not only dasatinib, but also imatinib and nilotinib, can be associated with subclinical PH. Noninvasive echocardiography is useful for screening, especially in older patients with long-term TKI treatment.


Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión Pulmonar/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Dasatinib/uso terapéutico , Ecocardiografía , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/diagnóstico por imagen , Mesilato de Imatinib/uso terapéutico , Leucemia Mieloide de Fase Crónica/complicaciones , Masculino , Persona de Mediana Edad , Pirimidinas/uso terapéutico , Resultado del Tratamiento , Insuficiencia de la Válvula Tricúspide/etiología , Adulto Joven
4.
Cell Immunol ; 320: 1-10, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28705375

RESUMEN

Perforin-2 is constitutively expressed in macrophages that are required for bacterial control. In this study, we found that perforin-2 is expressed in human macrophages with two isoforms: full-length perforin-2a and a splice variant, perforin-2b. Two isoforms show different subcellular distributions. Perforin-2a was predominantly localized to the membrane of endosome-like vesicles by a C-terminal transmembrane domain. In contrast, the short isoform perforin-2b lacking the transmembrane domain failed to localize to the membrane of vesicles. Furthermore, we determined that the pro-inflammatory stimuli LPS and TNF-α induced perforin-2a expression via the NF-κB pathway and triggered perforin-2a vesicles fusion with lysosomes. On the other hand, we detected the secretion of perforin-2b in response to LPS stimulation. Taken together, our data provide the evidence that membrane-bound and secretory isoforms of perforin-2 are present in human macrophages and may play important roles in immune defense.


Asunto(s)
Membrana Celular/metabolismo , Endosomas/metabolismo , Lisosomas/metabolismo , Macrófagos/inmunología , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Células Cultivadas , Humanos , Mediadores de Inflamación/inmunología , Lipopolisacáridos/inmunología , Fusión de Membrana , FN-kappa B/metabolismo , Proteínas Citotóxicas Formadoras de Poros/genética , Isoformas de Proteínas/genética , Transporte de Proteínas , Transducción de Señal , Factor de Necrosis Tumoral alfa/inmunología
5.
Jpn J Clin Oncol ; 47(5): 463-466, 2017 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-28334791

RESUMEN

Nivolumab, an anti-programmed death-1 antibody, is a breakthrough treatment for several malignancies. Its specific adverse effects caused by autoimmunity are termed immune-related adverse events, which involve several endocrine dysfunctions. Herein, we report two cases of isolated adrenocorticotropic hormone (ACTH) deficiency induced by nivolumab for the treatment of metastatic malignant melanoma. Case 1 was a 39-year-old man and Case 2 was a 50-year-old woman, both of whom presented with progressive melanoma. After 13 courses of nivolumab administration, both cases were diagnosed with adrenal insufficiency. Despite their basal serum ACTH and cortisol levels being low with little response to corticotropin-releasing hormone loading, other anterior pituitary hormone levels were preserved. Based on these endocrinological data, isolated ACTH deficiency was diagnosed. Magnetic resonance imaging showed normal pituitary glands, excluding hypophysitis. Finally, hydrocortisone replacement enabled the patients to continue nivolumab treatment. Therefore, it is important to consider isolated ACTH syndrome as a possible and potentially severe immune-related adverse event of nivolumab, even when head magnetic resonance imaging of affected cases does not show enlargement. We should not misdiagnose hidden immune-related adverse events behind general complaints of malignancies such as general malaise and appetite loss, to allow successful treatment using this beneficial immune checkpoint inhibitor.


Asunto(s)
Hormona Adrenocorticotrópica/deficiencia , Anticuerpos Monoclonales/efectos adversos , Autoinmunidad , Enfermedades del Sistema Endocrino/inducido químicamente , Enfermedades del Sistema Endocrino/inmunología , Enfermedades Genéticas Congénitas/inducido químicamente , Enfermedades Genéticas Congénitas/inmunología , Hipoglucemia/inducido químicamente , Hipoglucemia/inmunología , Hormona Adrenocorticotrópica/inmunología , Adulto , Autoinmunidad/efectos de los fármacos , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Nivolumab
6.
BMC Endocr Disord ; 13: 45, 2013 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-24106823

RESUMEN

BACKGROUND: Diffuse large B-cell lymphoma sometimes involves the endocrine organs, but involvement of both the pituitary and adrenal glands is extremely rare. Involvement of these structures can lead to hypopituitarism and adrenal insufficiency, and subsequent recovery of their function is rarely seen. The present report describes an extremely rare case of pituitary and adrenal diffuse large B-cell lymphoma presenting with hypopituitarism and adrenal insufficiency with subsequent recovery of pituitary and adrenal function after successful treatment of the lymphoma. CASE PRESENTATION: A 63-year-old Japanese man was referred to our hospital due to miosis, ptosis, hypohidrosis of his left face, polydipsia and polyuria. 18F-fluorodeoxy glucose positron emission tomography / computed tomography revealed hotspots in the pituitary gland, bilateral adrenal glands and the apex of his left lung. Surgical biopsy from the pituitary lesion confirmed the diagnosis of diffuse large B-cell lymphoma, with lymphoma cells replacing normal pituitary tissue. Endocrine function tests revealed adrenal insufficiency and panhypopituitarism, including a possible affection of the posterior pituitary. Hormone replacement therapy with desmopressin and hydrocortisone was started. Chemotherapy consisted of six courses of R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisolone) and two courses of high-dose methotrexate followed by autologous hematopoietic stem cell transplantation. Subsequently, his pituitary and bilateral adrenal lesions resolved, and serial endocrine function tests showed gradual improvement in pituitary and adrenal function. CONCLUSIONS: The present report describes an extremely rare case of diffuse large B-cell lymphoma with involvement of both the pituitary and bilateral adrenal glands. R-CHOP and high-dose methotrexate therapy followed by autologous hematopoietic stem cell transplantation was quite effective, and panhypopituitarism and adrenal insufficiency improved to almost normal values after successful treatment of the lymphoma with chemotherapy.

7.
Biol Pharm Bull ; 36(4): 574-8, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23392075

RESUMEN

Intravenous injection of bendamustine often causes venous irritation and also deteriorates the patient's quality of life. Thus, we evaluated the risk factors associated with venous irritation induced by bendamustine in patients with follicular lymphoma or mantle cell lymphoma. We also evaluated the effectiveness of intervention of changing the preparation procedure for bendamustine. All data were retrospectively collected from the electronic medical record system. In the initial analysis of the total 43 courses of bendamustine therapy, most patients (88%) were administered bendamustine with 250 mL of diluent according to the bendamustine package insert in Japan. The median concentration of bendamustine solution (0.56 mg/mL vs. 0.24 mg/mL) and the incidences of venous irritation (66% vs. 0%, p=0.01) were significantly different between the patients receiving bendamustine at 250 mL and 500 mL of diluent. Based on this result, we proposed changing the final volume of bendamustine dissolution from 250 to 500 mL, which is recommended in other countries. After this intervention, the incidence of venous irritation was significantly reduced from 58 to 20% (p=0.02). The incidence of venous irritation increased in a concentration-dependent manner (≤0.40 mg/mL: 6%; 0.41-0.60 mg/mL: 62%, p<0.001; >0.60 mg/mL: 75%, p<0.001). We conclude that a high concentration bendamustine solution is a risk factor for venous irritation and that 500 mL of diluent is ideal. To further reduce the incidence of venous irritation, the concentration of bendamustine solution is recommended to be 0.40 mg/mL or less.


Asunto(s)
Antineoplásicos/administración & dosificación , Irritantes/administración & dosificación , Compuestos de Mostaza Nitrogenada/administración & dosificación , Dolor/prevención & control , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Clorhidrato de Bendamustina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor/inducido químicamente , Rituximab , Venas
8.
Rinsho Ketsueki ; 54(4): 378-82, 2013 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-23666220

RESUMEN

Transfusion-related acute lung injury (TRALI) is a severe pulmonary complication following blood transfusions. We experienced a case of possible TRALI during the course of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). A 19-year-old woman was admitted to our hospital suffering from fever and abdominal pain. Her laboratory data revealed pancytopenia, liver damage, coagulopathy, and a high titer of EBV-DNA. Computed tomography showed hepatosplenomegaly and bone marrow aspiration revealed hemophagocytosis and the proliferation of atypical lymphocytes. A diagnosis of EBV-HLH was made and plasma exchange was performed. Severe hypoxia due to pulmonary edema developed two hours after starting the plasma transfusion. Methylprednisolone pulse therapy and non-invasive positive pressure ventilation ameliorated her respiratory condition. Anti-HLA class I and II antibodies were detected in donor sera and a cross-match test between patient lymphocytes and donor plasma was positive. To the best of our knowledge, this is the first case report of TRALI complicated with EBV-HLH. It is possible that hypercytokinemia accompanied by HLH was associated with the onset of TRALI.


Asunto(s)
Lesión Pulmonar Aguda/etiología , Infecciones por Virus de Epstein-Barr/inmunología , Linfohistiocitosis Hemofagocítica/terapia , Reacción a la Transfusión , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Femenino , Fiebre , Antígenos HLA/sangre , Humanos , Linfohistiocitosis Hemofagocítica/etiología , Linfohistiocitosis Hemofagocítica/inmunología , Edema Pulmonar/complicaciones , Adulto Joven
9.
Rinsho Ketsueki ; 53(6): 632-4, 2012 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-22790640

RESUMEN

We measured plasma levels of thrombopoietin (TPO) in several patients with thrombocytopenia. Similar to previous reports, TPO levels in aplastic anemia (N=9) were markedly higher than those in idiopathic thrombocytopenic purpura (N=10): 16.19+/-9.07 fmol/ml and 1.21+/-1.06 fmol/ml, respectively. In patients with secondary failure of platelet recovery (N=7) as well as primary failure after hematopoietic stem cell transplantation, TPO levels were very high, reflecting impaired platelet production due to GVHD, drug treatments, and infection. When using new drugs such as TPO-receptor agonists, measurement of TPO levels might be important to differentiate the mechanism of thrombocytopenia.


Asunto(s)
Trombocitopenia/sangre , Trombopoyetina/sangre , Adulto , Anciano , Anemia Aplásica/sangre , Humanos , Megacariocitos/citología , Megacariocitos/metabolismo , Persona de Mediana Edad , Recuento de Plaquetas , Púrpura Trombocitopénica Idiopática/sangre
10.
Clin Lymphoma Myeloma Leuk ; 20(7): e445-e453, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32312633

RESUMEN

BACKGROUND: We retrospectively analyzed patients with untreated aggressive adult T-cell leukemia/lymphoma who received the modified EPOCH (mEPOCH) regimen. PATIENTS AND METHODS: Patients received up to 6 mEPOCH cycles. Etoposide (50 mg/m2/day), doxorubicin (10 mg/m2/day), and vincristine (0.4 mg/m2/day) were each given as a continuous 96-hour infusion on days 1 to 4. Prednisolone (40 mg/m2/day) was given intravenously or orally on days 1 to 4 and then tapered and stopped on day 7, and carboplatin (dose calculated for each patient individually using Calvert's formula according to a target under the curve of 3 mg/mL/min) was given as a 2-hour intravenous infusion on day 6. RESULTS: In 103 patients, overall response rate and complete response rate were 58% and 25%, respectively. With a median follow-up of 8.9 months, the median survival time was 9.8 months (95% confidence interval, 7.2-13.9 months). The median progression-free survival (PFS) was 4.2 months (95% confidence interval, 3.4-5.7 months). Patients who completed ≥ 4 cycles experienced significantly better overall survival and PFS compared with those who completed < 4 cycles. Twenty-eight patients underwent allogeneic hematopoietic stem cell transplantation after mEPOCH and demonstrated significantly prolonged overall survival and PFS compared with those who did not undergo transplantation. CONCLUSION: The mEPOCH regimen is effective with tolerable adverse effects and may be an alternative treatment option for adult T-cell leukemia/lymphoma.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Ciclofosfamida/farmacología , Ciclofosfamida/uso terapéutico , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Etopósido/farmacología , Etopósido/uso terapéutico , Femenino , Humanos , Leucemia-Linfoma de Células T del Adulto/mortalidad , Leucemia-Linfoma de Células T del Adulto/patología , Masculino , Persona de Mediana Edad , Prednisona/farmacología , Prednisona/uso terapéutico , Supervivencia sin Progresión , Estudios Retrospectivos , Vincristina/farmacología , Vincristina/uso terapéutico
11.
Rinsho Ketsueki ; 49(11): 1541-7, 2008 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-19047785

RESUMEN

Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe complication of Epstein-Barr virus (EBV) infection. Interactions between EBV-infected T cells and activated macrophages cause several conditions such as pancytopenia, liver dysfunction and coagulopathy. We describe here two young adults with EBV-associated HLH with monoclonal proliferation of EBV-infected T cells within a short period after infectious mononucleosis as a primary infection. One patient was a 16-year-old man who developed severe pancytopenia and liver dysfunction two months after infectious mononucleosis. Bone marrow examination showed hemophagocytosis, and laboratory data demonstrated monoclonal proliferation of EBV-infected T cells. Several treatments such as immunosuppressive therapy, chemotherapy and hematopoietic stem cell transplantation were not effective, and the patient died of progressive disease. The other patient was a 19-year-old woman who developed thrombocytopenia and liver dysfunction two months after infectious mononucleosis. Findings of hemophagocytosis and monoclonal proliferation of EBV-infected T cells were similar to those in the first case. Clinical signs and symptoms were resolved completely by immunosuppressive therapy containing methyl-prednisolone and cyclosporine. Since these two cases each demonstrated a distinct clinical course, an investigation of the prognostic factors and treatment strategies for EBV-HLH is warranted.


Asunto(s)
Herpesvirus Humano 4 , Mononucleosis Infecciosa/complicaciones , Linfohistiocitosis Hemofagocítica/etiología , Linfocitos T/virología , Adolescente , Proliferación Celular , Resultado Fatal , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Inmunosupresores/uso terapéutico , Linfohistiocitosis Hemofagocítica/terapia , Masculino , Linfocitos T/patología , Resultado del Tratamiento , Adulto Joven
12.
Int J Hematol ; 108(3): 335-338, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29582334

RESUMEN

A case of acquired hemophilia A (AHA) that developed in a patient with autoimmune pancreatitis (AIP) is presented. A 64-year-old woman was diagnosed with AIP in 2007. The symptoms resolved with prednisolone (PSL). Although the dose of PSL was tapered to 7.5 mg/day for maintenance, serum IgG4 levels remained high. She suddenly presented with subcutaneous bleeding in 2015. Her activated partial thromboplastin time was prolonged (80.0 s). A mixing test showed an inhibitor pattern, factor VIII (FVIII) activity was less than 1%, and FVIII inhibitor was 290 BU/mL. She was diagnosed with AHA. Her serum IgG4 was elevated to 133 mg/dL. She was treated first with PSL alone, but she developed bladder tamponade. Cyclophosphamide and activated prothrombin complex concentrate were combined with PSL. She then achieved hemostasis, and FVIII inhibitor disappeared. FVIII inhibitor had been detected since PSL was tapered and AHA recurred two months later. An enzyme-linked immunosorbent assay showed that the inhibitor was mainly IgG4 and IgG1. This case suggests that elevation of IgG4 may be associated with the development of both AHA and AIP.


Asunto(s)
Enfermedades Autoinmunes/etiología , Inhibidores de Factor de Coagulación Sanguínea/sangre , Hemofilia A/etiología , Inmunoglobulina G/sangre , Pancreatitis/etiología , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/inmunología , Biomarcadores/sangre , Factor VIII , Femenino , Hemofilia A/diagnóstico , Hemofilia A/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Pancreatitis/sangre , Pancreatitis/tratamiento farmacológico , Pancreatitis/inmunología , Prednisolona/administración & dosificación
13.
Int J Hematol ; 105(4): 540-544, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27830541

RESUMEN

Aggressive NK-cell leukemia (ANKL) is characterized by systemic infiltration of Epstein-Barr virus (EBV)-associated natural killer cells and poor prognosis. We report a case of ANKL in which EBV-specific cytotoxic T lymphocytes (CTLs) were induced. A 41-year-old male suffered from fever, pancytopenia, and hepatosplenomegaly. The number of abnormal large granular lymphocytes in the bone marrow was increased and the cells were positive for CD56 and EBV-encoded small nuclear RNAs. The patient was diagnosed with ANKL and achieved a complete response following intensive chemotherapy. He then underwent allogeneic peripheral blood stem cell transplantation from his sister. Conditioning therapy consisted of total body irradiation and cyclophosphamide. Graft-versus-host disease prophylaxis consisted of cyclosporine and methotrexate. On day 31, complete donor chimerism was achieved and no acute graft-versus-host disease developed. The ANKL relapsed on day 80, and cyclosporine was rapidly tapered and chemotherapy was started. During hematopoietic recovery, the number of atypical lymphocytes increased, but they were donor-derived EBV-specific CTLs. The patient achieved a partial response and EBV viral load decreased to normal range. Unfortunately, ANKL worsen again when the CTLs disappeared from his blood. This is the first case report of ANKL in which induced EBV-specific CTLs may have contributed to disease control.


Asunto(s)
Herpesvirus Humano 4 , Leucemia Linfocítica Granular Grande/terapia , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Linfocitos T Citotóxicos/virología , Adulto , Manejo de la Enfermedad , Infecciones por Virus de Epstein-Barr/etiología , Infecciones por Virus de Epstein-Barr/terapia , Humanos , Leucemia Linfocítica Granular Grande/virología , Masculino , Trasplante de Células Madre de Sangre Periférica/métodos , Recurrencia , Linfocitos T Citotóxicos/trasplante , Donantes de Tejidos , Quimera por Trasplante , Trasplante Homólogo
14.
Leuk Lymphoma ; 46(3): 425-33, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15621834

RESUMEN

NS-398, a selective inhibitor of cyclooxygenase 2 (COX-2), has been reported to inhibit growth and induce apoptosis in several cancer cell lines that overexpress COX-2. However it has not been extensively studied in multiple myeloma (MM). Here, we studied the effects of COX-2 inhibitors on MM cell lines and primary myeloma patient cells. We investigated the effects of NS-398 on proliferation and apoptosis in three myeloma cell lines (PCM6, U266 and RPMI8226) and isolated CD138-positive cells from MM patients. Furthermore, the combined effects of NS-398 plus dexamethasone (Dex) or thalidomide (Thal) were investigated. All myeloma cell lines express COX-2. NS-398 inhibited growth and induced apoptosis in PCM6, RPMI8226 and CD138-positive MM cells in a time- and dose-dependent manner. At low concentrations (10 microM), NS-398 primarily induced growth arrest without affecting cell viability, but at higher concentrations (over 25 microM), apoptosis was induced. During the process of apoptosis, the number of Fas-positive cells increased. Downstream signals of Fas, such as caspase 8, 3 and 9, were also activated. On the other hand, protein levels of the Bcl-2 family did not change, although mitochondrial transmembrane potential ((Delta)(psi)m) was decreased. Combined incubation with Dex or Thal enhanced NS-398-induced growth inhibition and apoptosis in RPMI8226 cells. The combined effect of Dex was more potent than that of Thal. Our findings suggests that COX-2 plays an important role in regulation of apoptosis in myeloma cells, and COX-2 inhibitors might serve as an effective tool for future chemoprevention and/or treatment of myeloma.


Asunto(s)
Apoptosis/efectos de los fármacos , Inhibidores de la Ciclooxigenasa/farmacología , Genes bcl-2/fisiología , Mieloma Múltiple , Nitrobencenos/farmacología , Prostaglandina-Endoperóxido Sintasas/efectos de los fármacos , Sulfonamidas/farmacología , Caspasas/efectos de los fármacos , Caspasas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Dexametasona/farmacología , Relación Dosis-Respuesta a Droga , Proteína Ligando Fas , Genes bcl-2/efectos de los fármacos , Humanos , Glicoproteínas de Membrana/efectos de los fármacos , Glicoproteínas de Membrana/fisiología , Proteínas de la Membrana , Mieloma Múltiple/enzimología , Mieloma Múltiple/metabolismo , Talidomida/farmacología
15.
J Clin Exp Hematop ; 55(1): 39-43, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26106006

RESUMEN

A 64-year-old woman had suffered from painful livedo reticularis for 2 years and was referred to us due to fever, anasarca and paresthesia of the lower limbs. Serum proteinase-3-anti-neutrophil cytoplasmic antibody (ANCA) was positive. Abnormal lymphocytes were found in the cerebrospinal fluid and bone marrow. Skin biopsy revealed large atypical lymphoid cells with CD20 positivity lodged in the small vessels and neutrophilic infiltration into the arterial vascular wall with fibrinoid degeneration. A diagnosis of intravascular large B-cell lymphoma complicated by ANCA-associated vasculitis was made, and rituximab-containing chemotherapy followed by prednisolone was quite effective for both lymphoma and ANCA-associated vasculitis.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Biopsia , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Persona de Mediana Edad , Prednisolona/administración & dosificación , Prednisolona/uso terapéutico , Prednisona/uso terapéutico , Rituximab/administración & dosificación , Piel/patología , Resultado del Tratamiento , Vincristina/uso terapéutico
17.
Int J Hematol ; 76(1): 91-3, 2002 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12138903

RESUMEN

We describe the case of a 55-year-old man with adult T-cell leukemia/lymphoma (ATL) in first remission who underwent nonmyeloablative allogeneic peripheral blood stem cell transplantation with conditioning consisting of 4 courses of pentostatin and low-dose total body irradiation. Complete chimerism in peripheral blood was achieved on day 42 without severe myelosuppression. Concomitantly, the proviral DNA load for human T-cell leukemia virus I (HTLV-I) in peripheral blood mononuclear cells decreased below detectable limits and was still undetectable on day 270. This fact indicates that eradication of ATL cells is feasible by induction of an alloimmune response without high-dose chemoradiotherapy.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma de Células T del Adulto/terapia , Pentostatina/uso terapéutico , Linfocitos T Citotóxicos/virología , Acondicionamiento Pretrasplante/métodos , Adulto , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Irradiación Corporal Total/métodos
18.
Int J Hematol ; 78(5): 421-8, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14704034

RESUMEN

Interferon (IFN)-gamma is a survival factor for mature erythroid progenitor cells. To elucidate related survival mechanisms, we compared the role of phosphatidylinositol 3-kinase (PI3-kinase) in the survival signals of IFN-gamma and erythropoietin (EPO). Human erythroid colony-forming cells (ECFCs) purified from peripheral blood were used, and Ly294002 was used as a PI3-kinase inhibitor. Treating ECFCs with a high concentration of Ly294002 (50 micromol/L) in the presence of EPO and/or IFN-gamma reduced cell viability by inducing apoptosis. However, treating cells with a lower concentration of Ly294002 (10 micromol/L) did not affect the antiapoptotic function of IFN-gamma and abolished the antiapoptotic effect of EPO. Adding IFN-gamma or EPO induced Bcl-x expression in ECFCs, as determined by Western blotting, and expression was suppressed in the presence of Ly294002. We also examined the phosphorylation of the protein kinase Akt, the downstream target of PI3-kinase. EPO stimulation significantly increased the level of Akt phosphorylation, but IFN-gamma did not. These results suggest that IFN-gamma plays a role in preventing the apoptosis of erythroid progenitor cells by affecting Bcl-x expression, thereby reducing the disruption of the mitochondrial transmembrane potential via PI3-kinase pathways that are related to but distinct from the EPO pathway.


Asunto(s)
Apoptosis/efectos de los fármacos , Células Precursoras Eritroides/efectos de los fármacos , Eritropoyetina/farmacología , Interferón gamma/farmacología , Proteínas Serina-Treonina Quinasas , Transducción de Señal/efectos de los fármacos , Células Cultivadas/efectos de los fármacos , Cromonas/farmacología , Inhibidores Enzimáticos/farmacología , Células Precursoras Eritroides/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Morfolinas/farmacología , Fosfatidilinositol 3-Quinasas/fisiología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosforilación/efectos de los fármacos , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/genética , Especies Reactivas de Oxígeno/metabolismo , Proteínas Recombinantes/farmacología , Factor de Células Madre/farmacología , Proteína bcl-X
19.
Int J Hematol ; 79(4): 340-4, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15218962

RESUMEN

In human cancer, RCAS1 (the receptor-binding cancer antigen expressed on SiSo cells) on the surface of various kinds of tumor cells reportedly induces the apoptosis of T-cells and natural killer cells, resulting in evasion of the immune system. In the present study, an immunohistochemical analysis of RCAS1 expression was performed with lymph node specimens obtained from patients with adult T-cell leukemia/lymphoma (ATLL). Positive staining was seen in 15 (75%) of 20 cases and in all cases of patients with short survival times. In the cases of B-cell lymphomas, positive staining was seen in only 1 (13%) of 8 cases. These findings indicate that expression of RCAS1 may be associated with the evasion from immune surveillance of cells infected with human T-lymphotropic virus type I, resulting in the development of overt leukemia/lymphoma. Determination of RCAS1 expression may be useful for predicting the prognosis of patients with ATLL.


Asunto(s)
Antígenos de Neoplasias/análisis , Leucemia-Linfoma de Células T del Adulto/metabolismo , Adulto , Anciano , Cadherinas/análisis , Femenino , Humanos , Inmunohistoquímica , Leucemia-Linfoma de Células T del Adulto/mortalidad , Leucemia-Linfoma de Células T del Adulto/patología , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia
20.
Int J Hematol ; 77(4): 359-63, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12774924

RESUMEN

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1), which is recognized by the 22-1-1 monoclonal antibody (MoAb) against human uterine adenocarcinoma cell line SiSo, has been identified on various kinds of cancer cells. RCAS1 appears to be an apoptosis-associated protein that induces apoptosis in activated T-cells and erythroid progenitor cells. We previously demonstrated that monocytes/macrophages express RCAS1. In the present study, we investigated RCAS1 expression by 22-1-1 MoAb in histiocytic necrotizing lymphadenitis (HNL), which is characterized by necrotic lesions consisting of T-cells undergoing apoptosis and macrophages in proliferation. Expression of RCAS1 was analyzed by immunohistochemical staining in 9 cases of HNL and in 9 cases of reactive lymphadenitis used as a control. The ratio of RCAS1+ cells to CD68+ cells (monocytes/macrophages) was significantly higher in the patients with HNL than in the patients with reactive lymphadenitis (P = .0002; paired t test). Our findings suggest that RCAS1 expressed on macrophages may play an important role in the induction of activated T-cell apoptosis in cases of HNL.


Asunto(s)
Antígenos de Neoplasias/fisiología , Linfadenitis Necrotizante Histiocítica/patología , Macrófagos/fisiología , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales , Antígenos de Neoplasias/biosíntesis , Estudios de Casos y Controles , Femenino , Linfadenitis Necrotizante Histiocítica/etiología , Linfadenitis Necrotizante Histiocítica/inmunología , Humanos , Inmunohistoquímica , Linfadenitis , Activación de Linfocitos , Macrófagos/química , Masculino , Persona de Mediana Edad , Linfocitos T/patología
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