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1.
Blood Adv ; 7(11): 2418-2430, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-36583674

RESUMO

The tyrosine kinase inhibitor dasatinib is approved for Philadelphia chromosome-positive leukemia, including chronic myeloid leukemia (CML). Although effective and well tolerated, patients typically exhibit a transient lymphocytosis after dasatinib uptake. To date, the underlying physiological process linking dasatinib to lymphocytosis remains unknown. Here, we used a small rodent model to examine the mechanism of dasatinib-induced lymphocytosis, focusing on lymphocyte trafficking into and out of secondary lymphoid organs. Our data indicate that lymphocyte homing to lymph nodes and spleen remained unaffected by dasatinib treatment. In contrast, dasatinib promoted lymphocyte egress from spleen with kinetics consistent with the observed lymphocytosis. Unexpectedly, dasatinib-induced lymphocyte egress occurred independently of canonical sphingosine-1-phosphate-mediated egress signals; instead, dasatinib treatment led to a decrease in spleen size, concomitant with increased splenic stromal cell contractility, as measured by myosin light chain phosphorylation. Accordingly, dasatinib-induced lymphocytosis was partially reversed by pharmacological inhibition of the contraction-promoting factor Rho-rho associated kinase. Finally, we uncovered a decrease in spleen size in patients with CML who showed lymphocytosis immediately after dasatinib treatment, and this reduction was proportional to the magnitude of lymphocytosis and dasatinib plasma levels. In summary, our work provides evidence that dasatinib-induced lymphocytosis is a consequence of drug-induced contractility of splenic stromal cells.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Linfocitose , Humanos , Dasatinibe/efeitos adversos , Linfocitose/induzido quimicamente , Linfocitose/patologia , Baço/patologia , Pirimidinas/efeitos adversos , Tiazóis/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia
2.
Rev Esp Patol ; 55 Suppl 1: S69-S73, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36075667

RESUMO

Regression of primary renal cell carcinoma (RCC) is a rare phenomenon and for several reasons many of the reported cases have been questioned. We present a case that can be considered a true spontaneous and complete regression of a primary RCC. A 79-year-old female underwent nephrectomy because a renal tumor. At the time of surgery image studies showed a small para-aortic lymph node. The tumor measured 3cm and was analyzed completely. Histology showed a fibro-inflammatory lesion with necrosis, foamy macrophages and inflammatory cells. No neoplastic cells were observed and the lesion was interpreted as a localized type of xanthogranulomatous pyelonephritis. One year later a CT control scan, showed that the para-aortic lymph node had increased in size to 4cm. Fine needle aspiration revealed features of clear RCC. Metastatic dissemination was limited so surgical removal of the para-aortic lymph node was performed and the cytologic diagnosis confirmed.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Idoso , Biópsia por Agulha Fina , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Linfonodos/patologia , Nefrectomia/efeitos adversos , Nefrectomia/métodos
3.
Rev Esp Enferm Dig ; 109(6): 462-463, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28597682

RESUMO

Intrathoracic rupture of hydatid cyst of the liver is a rare but severe complication of echinococcal disease. It represent a serious condition responsible for lesions at 3 levels: hepatic, diaphragmatic, and pulmonary. Early diagnosis and management of septic associated complications are essential. We present the case of a 55 year old female patient with a giant hydatid cyst type CE 2 based on WHO Classification, communicating with the biliary tree and with a massive extension to the right hemithorax.


Assuntos
Fístula Biliar/diagnóstico por imagem , Fístula Biliar/cirurgia , Fístula Brônquica/diagnóstico por imagem , Fístula Brônquica/cirurgia , Albendazol/uso terapêutico , Animais , Procedimentos Cirúrgicos do Sistema Biliar , Colangiografia , Equinococose/diagnóstico por imagem , Equinococose/tratamento farmacológico , Echinococcus , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Radiografia Torácica
4.
Radiographics ; 34(2): 396-412, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24617687

RESUMO

Abdominal complications affect more than 80% of patients who undergo hematopoietic stem cell transplantation (HSCT) for treatment of benign or malignant hematologic disease and some solid tumors. HSCT can be performed using cells from bone marrow, peripheral blood, or umbilical cord blood. These stem cells may be from the patient him- or herself (autologous transplant), from relatives or nonrelatives with very similar human leukocyte antigen (allogeneic transplant), or from an identical twin (syngeneic transplant). Posttransplantation complications are classified according to the amount of time elapsed between transplantation and onset. Complications that occur during the first 100 days are divided into preengraftment phase complications (≤30 days after transplantation) and early posttransplantation phase complications (31-100 days after transplantation) and include infectious and noninfectious conditions such as hepatic veno-occlusive disease (VOD), hemorrhagic cystitis, neutropenic colitis, benign pneumatosis, and acute graft-versus-host disease (GVHD). Hepatic VOD, neutropenic colitis, and acute hemorrhagic cystitis are associated with the pretransplantation conditioning regimen. After the first 100 days, chronic GVHD and lymphoproliferative disease are the main complications. Computed tomography and ultrasonography are the primary imaging techniques used in HSCT patients and can help make an early diagnosis, grade the severity of impact, and (if necessary) recommend further investigations to confirm the diagnosis.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Abdome , Doenças do Sistema Digestório/diagnóstico , Doenças do Sistema Digestório/etiologia , Humanos , Tomografia Computadorizada por Raios X , Doenças Urológicas/diagnóstico , Doenças Urológicas/etiologia
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