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1.
Rinsho Ketsueki ; 61(2): 128-130, 2020.
Artículo en Japonés | MEDLINE | ID: mdl-32147612

RESUMEN

A 64-year-old male presented with a rapidly growing anterior mediastinal mass during the clinical course of atypical chronic myeloid leukemia. A needle biopsy performed for suspected myeloid sarcoma revealed the presence of Aspergillus abscess. Early diagnosis of mediastinal abscesses, which are associated with a high mortality rate, can prevent the progression of severity. Infectious abscesses should be considered for prompt qualitative diagnosis in patients with mediastinal masses. Thymoma, germ cell tumor, and malignant lymphoma are the most common anterior mediastinal tumors, whereas infectious abscesses should also be considered when myeloid sarcoma is suspected in patients with an underlying myeloid tumor.


Asunto(s)
Leucemia Mieloide Crónica Atípica BCR-ABL Negativa , Neoplasias del Mediastino , Timoma , Neoplasias del Timo , Absceso , Aspergillus , Humanos , Masculino , Persona de Mediana Edad
2.
Kurume Med J ; 2019 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-31787704

RESUMEN

High-dose chemotherapy and autologous stem cell transplantation is too toxic for elderly patients with relapsed or refractory (DLBCL). Therefore, tolerable and efficient salvage regimens for elderly patients are greatly needed. In this study, therapy with rituximab, gemcitabine, dexamethasone, and cisplatin (R-GDP) will be performed every 4 weeks, and an interim evaluation will be performed after the completion of the 3rd course. If a complete response (CR) is achieved at the time of interim evaluation, 1 course of R-GDP therapy and 2 courses of monotherapy with rituximab will be additionally performed. If a partial response (PR) is achieved, 3 courses of R-GDP therapy will be additionally conducted. In patients without a PR or CR by the time of the interim evaluation, treatment will be discontinued. Treatment will also be discontinued at any point if disease progression is observed during protocol treatment. After the completion of the final course of R-GDP therapy, final effects of the regimen will be evaluated. A primary endpoint is the efficacy of R-GDP therapy (CR and response rates). This is the first multicenter phase II clinical study of R-GDP therapy to examine post-treatment activities of daily living in addition to the safety and efficacy of treatment in elderly patients with relapsed or refractory transplant ineligible DLBCL.

3.
Rinsho Ketsueki ; 59(4): 383-388, 2018.
Artículo en Japonés | MEDLINE | ID: mdl-29743396

RESUMEN

Congenital combined deficiency of coagulation factor V (FV) and factor VIII (FVIII) (F5F8D) is a rare autosomal recessive bleeding disorder caused by mutations in lectin mannose-binding type 1 (LMAN1) or multiple coagulation factor deficiency 2 (MCFD2) encoding chaperone molecules involved in the intracellular transport of FV and FVIII. Here, we report a case of F5F8D in an elderly patient diagnosed with hematoma after a right thigh injury. A 71-year-old male had a history of abnormal bleeding after tooth extraction and cholecystectomy. The patient injured his right thigh with a kitchen knife; he was urgently hospitalized to a referral hospital 8 days later due to the occurrence of hematoma at the same site. Owing to prolongation of the coagulation time (PT 16.1 s, 1.72; APTT, 66.1 s), he received hemostatic treatment with fresh-frozen plasma. He was then referred to our hospital for examination of PT and APTT prolongation. FV and FVIII activities were moderately decreased to about 15%, and no inhibitor was detected. Whole-exome sequencing identified a previously reported homozygous nonsense mutation in LMAN1, revealing F5F8D in the proband. In this case, FFP infusion alone was not sufficient for increasing coagulation factor activities. Definitive diagnosis of F5F8D provides him with the treatment option with FVIII concentrates.


Asunto(s)
Deficiencia del Factor V/diagnóstico , Hemofilia A/diagnóstico , Hemorragia/etiología , Muslo/lesiones , Anciano , Factor V , Factor VIII , Humanos , Masculino
4.
Int J Hematol ; 108(1): 39-46, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29594921

RESUMEN

In the era of novel therapeutic agents for multiple myeloma (MM), both the significance of achieving the plateau phase and the efficacy of subsequent maintenance therapy remain unclear. In the present study, we evaluated the efficacy and safety of bortezomib maintenance therapy (biweekly for 1 year) in transplant-ineligible MM patients who plateaued after bortezomib-based induction therapy. Of 36 evaluable patients, the overall response rate during induction therapy was 61%, with a stringent complete response in 6%, a complete response in 6%, a very good partial response in 17%, and a partial response in 33%. Twenty patients achieved the plateau phase and subsequently received bortezomib maintenance therapy. Median progression-free survival from the induction and maintenance therapies was 13.8 months (95% confidence interval, 11.4-23.7 months) and 10.7 months (95% confidence interval, 3.7-10.7 months), respectively. During maintenance therapy, there were no cases with grade ≥ 2 peripheral neuropathy, nor was there any improvement in the quality of the response. In conclusion, although maintenance therapy with biweekly bortezomib for up to 1 year was feasible, plateau-oriented bortezomib induction therapy followed by bortezomib maintenance therapy was not adequate in newly diagnosed transplant-ineligible MM patients.


Asunto(s)
Antineoplásicos/administración & dosificación , Bortezomib/administración & dosificación , Quimioterapia de Inducción , Quimioterapia de Mantención , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Resultado del Tratamiento
5.
J Clin Exp Hematop ; 58(1): 10-16, 2018 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-29415976

RESUMEN

Recent studies have revealed the clinical and biological features of stage I follicular lymphoma (FL), but information about patients with stage I FL who underwent total resection after tissue biopsy is limited. Among 305 FL patients diagnosed between 2001 and 2013, clinical stage I disease was observed in 36 patients. Of these, 18 patients underwent total resection after diagnostic tissue biopsy. We used 18F-fluorodeoxyglucose positron emission CT for staging assessment in 13 of 18 patients (72.2%). The median age was 56.5 years. Six patients (33.3%) were male. The soluble interleukin-2 receptor alpha concentration was significantly lower than in patients with residual disease. Among these 18 patients, 7 patients (38.9%) were treated with a "watch-and-wait" (WW) policy, 7 (38.9%) were treated with involved-field irradiation, and 4 (22.2%) received systemic chemotherapy. Patients with resected disease were treated with significantly different strategies from those with residual disease (p = 0.0026). Five patients experienced relapse during follow-up (median follow-up: 48.2 months). All relapses were distant from the primary site, irrespective of treatment strategy. Among all stage I patients, disease resection was not a significant factor for survival (p = 0.9294). Collectively, the choice of treatment strategy was significantly influenced by patient status. Resection status was not significantly associated with survival after several treatment strategies.


Asunto(s)
Glucosa-6-Fosfato/análogos & derivados , Linfoma Folicular , Tomografía de Emisión de Positrones , Anciano , Supervivencia sin Enfermedad , Femenino , Glucosa-6-Fosfato/administración & dosificación , Humanos , Linfoma Folicular/diagnóstico por imagen , Linfoma Folicular/mortalidad , Linfoma Folicular/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasia Residual , Tasa de Supervivencia
7.
Int J Hematol ; 105(4): 478-484, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27873176

RESUMEN

Chemotherapy-induced nausea and vomiting (CINV) is a significant side effect in multiple myeloma (MM) patients receiving high-dose melphalan treatment followed by autologous stem cell transplantation (ASCT). We evaluated the efficacy and safety of a triple antiemetic combination of palonosetron, aprepitant, and low-dose dexamethasone in 24 MM patients who received melphalan conditioning (100 mg/m2 on days 1-2) before ASCT (on day 4). Intravenous palonosetron (0.75 mg on day 1), oral aprepitant (125 mg on day 1; 80 mg on days 2-4), and intravenous dexamethasone (6.6 mg on days 1-4) were administered for prevention of CINV. Complete response (no emesis and no rescue antiemetic) and complete control (no emesis, no rescue antiemetic, and no more than mild nausea) rates were 75 and 68% during the overall phase (0-120 h), while they were 88 and 86% in the acute phase (0-48 h), 75 and 68% in the delayed phase (48-120 h), and 67 and 59% in the extended phase (120-168 h), respectively. There were no serious adverse events related to the antiemetic therapy. In conclusion, the three-antiemetic regimen consisting of palonosetron, aprepitant, and dexamethasone was safe and effective for controlling CINV due to high-dose melphalan treatment, especially during the delayed phase.


Asunto(s)
Antieméticos/uso terapéutico , Quimioterapia Combinada/métodos , Melfalán/administración & dosificación , Mieloma Múltiple/terapia , Náusea y Vómito Posoperatorios/prevención & control , Trasplante Autólogo/métodos , Adulto , Anciano , Aprepitant , Dexametasona/administración & dosificación , Humanos , Isoquinolinas/administración & dosificación , Persona de Mediana Edad , Morfolinas/administración & dosificación , Agonistas Mieloablativos/uso terapéutico , Palonosetrón , Náusea y Vómito Posoperatorios/tratamiento farmacológico , Quinuclidinas/administración & dosificación , Resultado del Tratamiento
8.
Rinsho Ketsueki ; 57(6): 771-3, 2016 06.
Artículo en Japonés | MEDLINE | ID: mdl-27384859

RESUMEN

We describe a patient who developed repeated rituximab-induced serum sickness (RISS) followed by anaphylaxis soon after the third administration of rituximab at relapse. A 65-year-old woman with Sjögren's syndrome and relapsed mucosal associated lymphoma tissue (MALT) lymphoma of the lung underwent rituximab monotherapy (375 mg/m(2)/week). Several days after the second exposure to rituximab, she developed a rash, fever, and arthralgia. These symptoms showed relief, but a severe anaphylactic reaction occurred when she was treated with rituximab for the third time. Although a rare complication in patients with lymphoma, clinicians should be aware of RISS symptoms and avoid repeatedly administering rituximab to such patients.


Asunto(s)
Anafilaxia/inducido químicamente , Antineoplásicos/efectos adversos , Rituximab/efectos adversos , Enfermedad del Suero/inducido químicamente , Anciano , Antineoplásicos/uso terapéutico , Femenino , Humanos , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Rituximab/uso terapéutico
9.
Int J Hematol ; 102(3): 271-7, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26177588

RESUMEN

Lenalidomide treatment in combination with dexamethasone and/or chemotherapy is associated with a significant risk of venous thromboembolism (VTE) in patients with multiple myeloma (MM). However, the incidence of asymptomatic VTE in lenalidomide-treated MM patients remains unclear. A total of 80 relapsed and refractory MM patients treated with lenalidomide-containing regimens in a single institution between July 2010 and July 2014 were retrospectively analyzed. Of these, eight patients had asymptomatic VTE before starting lenalidomide. The remaining 72 patients received thromboprophylaxis with low-dose aspirin (100 mg daily) and monitoring of plasma D-dimer levels on each visit. During the median follow-up time of 7.3 months (range 1.0-43.5 months), 29 patients (40.3 %) showed an elevation of D-dimer (≥2.5 µg/mL), and 13 (18.1 %) showed asymptomatic VTE in a lower extremity. Median time to asymptomatic VTE events from initiation of lenalidomide treatment was 3.0 months (range 1.0-13.1 months). All patients having an asymptomatic VTE continued lenalidomide treatment on warfarinization (target international normalized ratio 1.5-2.5), and none of them developed symptomatic VTE. In conclusion, an asymptomatic VTE event occurred in 18 % of Japanese MM patients receiving lenalidomide-containing therapy despite aspirin prophylaxis. Serial monitoring of plasma D-dimer levels and early intervention may help to prevent symptomatic or lethal VTE events.


Asunto(s)
Mieloma Múltiple/tratamiento farmacológico , Talidomida/análogos & derivados , Tromboembolia Venosa/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Lenalidomida , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/complicaciones , Estudios Retrospectivos , Talidomida/administración & dosificación , Tromboembolia Venosa/sangre , Tromboembolia Venosa/etiología
10.
Rinsho Ketsueki ; 55(5): 563-9, 2014 05.
Artículo en Japonés | MEDLINE | ID: mdl-24881923

RESUMEN

A 40-year-old man was diagnosed with Langerhans cell histiocytosis (LCH) in October 2010. His LCH was refractory to conventional chemotherapy, and thus worsened to Langerhans cell sarcoma (LCS) in May 2011. Although we repeated combination chemotherapies, new infiltration of the liver and bone marrow, as well as primary lesions of the bone, lymph nodes, and skin, appeared. These intensive chemotherapies caused candida liver abscesses, invasive aspergillosis, disseminated varicella zoster virus infection and bacterial sepsis. We administered bendamustine for chemotherapy, which resulted in a partial response (PR) with no severe adverse events. Because of pancytopenia caused by secondary myelodysplastic syndrome, we stopped the bendamustine chemotherapy after two courses. PR was maintained for 4 months. We plan to perform allogeneic hematopoietic stem cell transplantation from a sibling donor after a conditioning regimen. Optimal therapy for adult LCH, which is a rare and treatment-resistant disease, has yet to be established. Bendamustine is a potential chemotherapeutic agent for standard treatment of LCS.


Asunto(s)
Antineoplásicos/uso terapéutico , Sarcoma de Células de Langerhans/tratamiento farmacológico , Compuestos de Mostaza Nitrogenada/uso terapéutico , Adulto , Clorhidrato de Bendamustina , Terapia Combinada , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Sarcoma de Células de Langerhans/patología , Sarcoma de Células de Langerhans/terapia , Masculino , Compuestos de Mostaza Nitrogenada/efectos adversos , Acondicionamiento Pretrasplante , Resultado del Tratamiento
11.
Mol Cancer Res ; 12(10): 1449-59, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24939643

RESUMEN

UNLABELLED: Involvement of Ras in cancer initiation is known, but recent evidence indicates a role in cancer progression, including metastasis and invasion; however, the mechanism is still unknown. In this study, it was determined that human lung cancer cells with Ras mutations, among other popular mutations, showed significantly higher expression of CUB domain-containing protein 1 (CDCP1) than those without. Furthermore, activated Ras clearly induced CDCP1, whereas CDCP1 knockdown or inhibition of CDCP1 phosphorylation by Src-directed therapy abrogated anoikis resistance, migration, and invasion induced by activated-Ras. Activation of MMP2 and secretion of MMP9, in a model of Ras-induced invasion, was found to be regulated through induction of phosphorylated CDCP1. Thus, CDCP1 is required for the functional link between Ras and Src signaling during the multistage development of human malignant tumors, highlighting CDCP1 as a potent target for treatment in the broad spectrum of human cancers associated with these oncogenes. IMPLICATIONS: CDCP1 protein induced by oncogenic Ras/Erk signaling is essential for Ras-mediated metastatic potential of cancer cells.


Asunto(s)
Antígenos CD/metabolismo , Moléculas de Adhesión Celular/metabolismo , Genes ras , Sistema de Señalización de MAP Quinasas , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Anoicis , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Metaloproteinasas de la Matriz/metabolismo , Mutación/genética , Invasividad Neoplásica , Metástasis de la Neoplasia , Neoplasias/genética , Familia-src Quinasas/metabolismo
12.
Cancer Sci ; 104(7): 865-70, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23510015

RESUMEN

CUB (C1r/C1s, urchin embryonic growth factor, BMP1) domain-containing protein 1 (CDCP1) has been implicated in promoting metastasis of cancer cells through several mechanisms, including the inhibition of anoikis, which is cell death triggered by the loss of extracellular matrix interactions. However, the mechanism inhibiting cell death regulated by CDCP1 remains elusive. Inhibition of CDCP1 expression using small interfering RNA (siRNA) induced the cell death of suspended cancer cells without cleaving caspase-3, a marker of apoptosis; cell death was not inhibited by a general caspase inhibitor, suggesting that the loss of CDCP1 induces caspase-independent cell death. In contrast, knockdown of CDCP1 as well as protein kinase Cδ (PKCδ), a downstream effector of CDCP1, in a suspension culture of lung cancer cells resulted in marked induction of membranous microtubule-associated protein 1 light chain 3 (LC3)-II protein, a hallmark of autophagy, and caused the formation of an autophagosome structure visualized using green fluorescent protein-tagged LC3-II. Expression and phosphorylation of exogenous CDCP1 by Fyn kinase reduced the formation of autophagosomes and inhibited phosphorylation of CDCP1 by PP2, a Src kinase inhibitor or inhibited PKCδ by rottlerin, stimulating autophagosome formation. Moreover, death of suspended lung cancer cells induced by CDCP1 siRNA or by PKCδ siRNA was reduced by the autophagy inhibitor 3-methyladenine. These results indicate that CDCP1-PKCδ signaling plays a critical role in inhibiting autophagy, which is responsible for anoikis resistance of lung cancer cells.


Asunto(s)
Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Antígenos CD/genética , Antígenos CD/metabolismo , Autofagia/genética , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Adenina/análogos & derivados , Adenina/farmacología , Adenocarcinoma/genética , Adenocarcinoma del Pulmón , Anoicis/efectos de los fármacos , Anoicis/genética , Autofagia/efectos de los fármacos , Caspasa 3/genética , Caspasa 3/metabolismo , Moléculas de Adhesión Celular/antagonistas & inhibidores , Muerte Celular/efectos de los fármacos , Muerte Celular/genética , Línea Celular Tumoral , Humanos , Neoplasias Pulmonares/genética , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas de Neoplasias/antagonistas & inhibidores , Fagosomas/efectos de los fármacos , Fagosomas/genética , Fagosomas/metabolismo , Fagosomas/patología , Fosforilación/efectos de los fármacos , Fosforilación/genética , Proteína Quinasa C-delta/genética , Proteína Quinasa C-delta/metabolismo , Proteínas Proto-Oncogénicas c-fyn/genética , Proteínas Proto-Oncogénicas c-fyn/metabolismo , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Familia-src Quinasas/genética , Familia-src Quinasas/metabolismo
13.
Mol Cancer Res ; 11(6): 628-37, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23439492

RESUMEN

Complement C1r/C1s, Uegf, Bmp1 (CUB) domain-containing protein 1 (CDCP1) is a transmembrane protein that regulates anchorage-independent growth and cancer cell migration and invasion. Expression of CDCP1 is detected in a number of cancer cell lines and tissues and is closely correlated with poor prognosis. Invadopodia are actin-based protrusions on the surface of invasive cancer cells that promote the degradation of the extracellular matrix (ECM) via localized proteolysis, which is mainly mediated by membrane type 1 matrix metalloproteinase (MT1-MMP). MT1-MMP is accumulated at invadopodia by targeted delivery via membrane trafficking. The present study shows that CDCP1 is required for ECM degradation by invadopodia in human breast cancer and melanoma cells. CDCP1 localized to caveolin-1-containing vesicular structures and lipid rafts and was detected in close proximity to invadopodia. Further biochemical analysis revealed that substantial amounts of CDCP1 existed in the Triton X-100 insoluble lipid raft fraction. CDCP1 was coimmunoprecipitated with MT1-MMP and colocalized with MT1-MMP at the vesicular structures. The siRNA-mediated knockdown of the CDCP1 expression markedly inhibited MT1-MMP-dependent ECM degradation and Matrigel invasion and reduced the accumulation of MT1-MMP at invadopodia, as shown by immunofluorescence analysis. These results indicate that CDCP1 is an essential regulator of the trafficking and function of MT1-MMP- and invadopodia-mediated invasion of cancer cells.


Asunto(s)
Antígenos CD/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Moléculas de Adhesión Celular/metabolismo , Metaloproteinasa 14 de la Matriz/metabolismo , Melanoma/metabolismo , Melanoma/patología , Proteínas de Neoplasias/metabolismo , Seudópodos/patología , Caveolina 1/metabolismo , Línea Celular Tumoral , Vesículas Citoplasmáticas/efectos de los fármacos , Vesículas Citoplasmáticas/metabolismo , Matriz Extracelular/metabolismo , Femenino , Humanos , Espacio Intracelular/metabolismo , Microdominios de Membrana/metabolismo , Invasividad Neoplásica , Unión Proteica , Transporte de Proteínas , Seudópodos/enzimología , ARN Interferente Pequeño/metabolismo
14.
Cancer Res ; 70(12): 5136-46, 2010 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-20501830

RESUMEN

CUB domain-containing protein 1 (CDCP1) is a membrane protein that is highly expressed in several solid cancers. We reported previously that CDCP1 regulates anoikis resistance as well as cancer cell migration and invasion, although the underlying mechanisms have not been elucidated. In this study, we found that expression of CDCP1 in pancreatic cancer tissue was significantly correlated with overall survival and that CDCP1 expression in pancreatic cancer cell lines was relatively high among solid tumor cell lines. Reduction of CDCP1 expression in these cells suppressed extracellular matrix (ECM) degradation by inhibiting matrix metalloproteinase-9 secretion. Using the Y734F mutant of CDCP1, which lacks the tyrosine phosphorylation site, we showed that CDCP1 regulates cell migration, invasion, and ECM degradation in a tyrosine phosphorylation-dependent manner and that these CDCP1-associated characteristics were inhibited by blocking the association of CDCP1 and protein kinase Cdelta (PKCdelta). CDCP1 modulates the enzymatic activity of PKCdelta through the tyrosine phosphorylation of PKCdelta by recruiting PKCdelta to Src family kinases. Cortactin, which was detected as a CDCP1-dependent binding partner of PKCdelta, played a significant role in migration and invasion but not in ECM degradation of pancreatic cells. These results suggest that CDCP1 expression might play a crucial role in poor outcome of pancreatic cancer through promotion of invasion and metastasis and that molecules blocking the expression, phosphorylation, or the PKCdelta-binding site of CDCP1 are potential therapeutic candidates.


Asunto(s)
Antígenos CD/metabolismo , Moléculas de Adhesión Celular/metabolismo , Movimiento Celular/fisiología , Matriz Extracelular/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Antígenos CD/genética , Western Blotting , Adhesión Celular , Moléculas de Adhesión Celular/antagonistas & inhibidores , Moléculas de Adhesión Celular/genética , Proliferación Celular , Cortactina/antagonistas & inhibidores , Cortactina/genética , Cortactina/metabolismo , Humanos , Técnicas para Inmunoenzimas , Inmunoprecipitación , Metástasis Linfática , Metaloproteinasa 9 de la Matriz/metabolismo , Invasividad Neoplásica , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/genética , Fosforilación , Pronóstico , Proteína Quinasa C-delta/antagonistas & inhibidores , Proteína Quinasa C-delta/genética , Proteína Quinasa C-delta/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Células Tumorales Cultivadas , Tirosina/metabolismo
15.
Int J Hematol ; 90(2): 239-242, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19588217

RESUMEN

Paraneoplastic neuropathies have rarely been reported in patients with hematological malignancies. We report herein the case of a 65-year-old Japanese woman with chronic myelomonocytic leukemia (CMML) accompanying chronic inflammatory demyelinating polyneuropathy (CIDP). She had been diagnosed with refractory anemia and subsequently developed CMML with cytogenetic abnormalities including t(3;8)(q26;q24). While regenerating bone marrow following induction chemotherapy, she complained of numbness in the lower legs and then became unable to walk. Clinical and electrophysiological features were consistent with CIDP. Intravenous immunoglobulin treatment was insufficient, although corticosteroids reduced neurological symptoms. This case suggests CIDP as one of the autoimmune phenomena associated with myelodysplastic syndrome and immunosuppressive treatment represents an effective therapy.


Asunto(s)
Enfermedades Autoinmunes/complicaciones , Leucemia Mielomonocítica Crónica/complicaciones , Síndromes Mielodisplásicos/inmunología , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/complicaciones , Grupo de Ascendencia Continental Asiática , Enfermedades Autoinmunes/inmunología , Médula Ósea/patología , Femenino , Humanos , Leucemia Mielomonocítica Crónica/inmunología , Leucemia Mielomonocítica Crónica/patología , Persona de Mediana Edad , Síndromes Mielodisplásicos/patología , Conducción Nerviosa , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/inmunología
16.
Am J Pathol ; 172(6): 1729-39, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18467693

RESUMEN

CUB-domain-containing protein 1 (CDCP1) is a type-I transmembrane protein that is highly expressed in colon, breast, and lung cancers. We recently revealed that CDCP1 is associated with and phosphorylated by Src family kinases and is involved in the regulation of anchorage independence of certain lung cancer cell lines. In this study, we examined whether CDCP1 is involved in the regulation of tumor progression of scirrhous gastric cancer, which is a diffusely infiltrative carcinoma with high invasion potential. Expression and phosphorylation levels of CDCP1 correlated with the invasive potential of scirrhous gastric cancers. Reduction of CDCP1 expression by siRNA suppressed migration, invasion, and anchorage independence without affecting the proliferation of highly invasive scirrhous gastric cancer cells. However, CDCP1 overexpression promoted gastric cancer cell migration with low potential of invasion. Loss of CDCP1 suppressed invasion and dissemination of cancer cells that were orthotopically implanted in the gastric wall of nude mice. Expression and phosphorylation of CDCP1 were also detected in cancer cells of surgically resected tissues of human scirrhous gastric cancer by immunohistochemical analysis. Our results suggest that CDCP1 promotes invasion and peritoneal dissemination of cancer cells through the regulation of cell migration and anchorage independence. Therefore, it is both a potential prognostic and therapeutic target in certain types of gastrointestinal cancers, and suppression of its phosphorylation might be a useful strategy for modulating cancer metastasis.


Asunto(s)
Adenocarcinoma Escirroso/metabolismo , Antígenos CD/fisiología , Moléculas de Adhesión Celular/fisiología , Proteínas de Neoplasias/fisiología , Neoplasias Peritoneales/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma Escirroso/secundario , Animales , Línea Celular Tumoral , Movimiento Celular , Humanos , Ratones , Ratones Desnudos , Invasividad Neoplásica , Trasplante de Neoplasias , Neoplasias Peritoneales/secundario , Fosforilación , Neoplasias Gástricas/patología , Trasplante Heterólogo
17.
Rinsho Ketsueki ; 49(2): 82-8, 2008 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-18341037

RESUMEN

We retrospectively analyzed the clinical course and prognosis of 11 patients with angioimmunoblastic T-cell Lymphoma (AILT). Median patient age was 62 years old (range 39 to 85). All patients were in clinical stage III or IV. Clinical features included B symptoms, hepatosplenomegaly, skin rushes, pleural effusion, ascites and polyclonal hypergammaglobulinemia. The disease can be classified into three categories based on histological findings: 3 cases of AILT with hyperplastic germinal centers, 4 cases of typical AILT, and 4 cases of AILT with numerous clear cells. As the initial therapy, 10 patients received combination chemotherapy and only 1 patient received autologous peripheral blood stem cell transplantation. Seven patients achieved CR and 4 showed PD. The response rate was 63% and the median survival time was 20 months. One patient survived in CR for 122 months. Patients with AILT demonstrating hyperplastic germinal centers and no bone marrow infiltration were able to achieve long-term survival. The survival time of AILT demonstrated a wide range. It was thought that further consideration of the prognostic factors and stratification was required.


Asunto(s)
Linfadenopatía Inmunoblástica/terapia , Linfoma de Células T/terapia , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Linfadenopatía Inmunoblástica/clasificación , Linfadenopatía Inmunoblástica/mortalidad , Linfadenopatía Inmunoblástica/patología , Linfoma de Células T/clasificación , Linfoma de Células T/mortalidad , Linfoma de Células T/patología , Masculino , Persona de Mediana Edad , Trasplante de Células Madre de Sangre Periférica , Pronóstico , Tasa de Supervivencia
19.
Pathol Oncol Res ; 13(1): 74-7, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17387393

RESUMEN

We present three cases of follicular lymphoma (FL) exhibiting prominent sclerosis (sclerosing variant of follicular lymphoma), resembling inflammatory pseudotumor (IPT) of the lymph node, arising from mesenteric lymph node. Clinically all three cases represented bulky masses of the mesenteric lymph node. Histologically, the lesions were characterized by neoplastic lymphoid follicles separated by stromal collagenization and sclerotic process, with cellular infiltrate extending into the adjacent adipose tissue. The lesions contained variable cellular spindle cell proliferation and inflammatory infiltrate including numerous reactive T cells and histiocytes. Small capillary proliferation with vascular change was also noted. Immunohistochemical study demonstrated the myofibroblastic nature of the spindle cells. Moreover, neoplastic follicles were composed of intermediate to medium-sized lymphocytes, somewhat resembling reactive lymphoid aggregates. The overall histomorphological findings of the three lesions were similar to those of IPT of the lymph node. However, CD10, Bcl-2 and Bcl-6 immunostaining demonstrated the neoplastic nature of the lymphoid follicles and the lesions were diagnosed as FL grade 1. The present three cases indicate that the sclerosing variant of grade 1 FL should be added to the differential diagnosis from IPT of the lymph node.


Asunto(s)
Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/patología , Linfoma Folicular/patología , Anciano , Colágeno/biosíntesis , Diagnóstico Diferencial , Femenino , Fibronectinas/biosíntesis , Humanos , Inmunohistoquímica , Ganglios Linfáticos/patología , Linfoma Folicular/diagnóstico , Masculino , Mesenterio , Persona de Mediana Edad , Esclerosis/patología
20.
Rinsho Ketsueki ; 47(7): 656-60, 2006 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-16910577

RESUMEN

A 51-year-old man visited our hospital because of fever in 2003. With the discovery of the presence of a chest wall tumor, pleural effusion and M-protein, and increased plasma cells in the bone marrow, a diagnosis of multiple myeloma was established. Since the effect of combination chemotherapy followed by tandem auto-PBSCT lasted only one year, thalidomide and dexamethasone administration was started in November 2004. However, three months later, his lower limbs became swollen. Elevation of fibrin degradation product (FDP) and computed tomography findings suggested deep vein thrombosis and pulmonary embolism. With heparin and warfarin, these thromboses disappeared. Furthermore, chemotherapy strategies in addition to thalidomide were safely performed with anti-coagulation therapy. As thalidomide has become an accepted component in therapeutic strategies for multiple myeloma, careful attention must be paid to the prevention of thrombosis.


Asunto(s)
Dexametasona/administración & dosificación , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Embolia Pulmonar/etiología , Talidomida/administración & dosificación , Trombosis de la Vena/etiología , Inhibidores de la Angiogénesis/administración & dosificación , Antineoplásicos Hormonales/administración & dosificación , Esquema de Medicación , Humanos , Masculino , Persona de Mediana Edad
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