RESUMO
A 67-years old woman was referred to our hospital in October 1992 with thrombocytopenia and splenomegaly. A bone marrow biopsy revealed decreased cellularity, with moderately increased reticulin fibrosis and discrete dysmorphic megakaryocytes but no signs of dysplasia in the erythroid or the myeloid lineages. The karyotype of the bone marrow cells was t(12;17) (q24;q11). She was diagnosed as having agnogenic myeloid metaplasia. The patient received only blood transfusions until November 1998 when leukocytosis with immature cells started to appear. The bone marrow aspiration analysis showed increased cellularity and chromosomal analysis demonstrated the presence of t(9;22) (q34;q11) without any t(12;17) (q24;q11) abnormality. Because IFN therapy and oral administration of hydroxyurea did not show any cytological effect, administration of imatinib mesylate was started from December 2001. The Ph-positive cells as demonstrated by the FISH method had decreased to 7% by April 2003. But the t(12;17)(q24;q11) positive clones, which were observed on the first admission, again appeared in the peripheral blood, whereas Ph clones were detected in only one out of 24 cells examined. During the course of treatment with imatinib mesylate for chronic myelogenous leukemia which developed from agnogenic myeloid metaplasia accompanied with t(12;17)(q24;q11) translocation, the co-existence of two clones derived from, possibly, stem cells was identified.
Assuntos
Antineoplásicos/efeitos adversos , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 17/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/efeitos adversos , Mielofibrose Primária/etiologia , Pirimidinas/efeitos adversos , Translocação Genética , Idoso , Antineoplásicos/uso terapêutico , Benzamidas , Feminino , Humanos , Mesilato de Imatinib , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Piperazinas/uso terapêutico , Mielofibrose Primária/genética , Pirimidinas/uso terapêutico , RecidivaRESUMO
A 47-year-old woman was admitted to our hospital in December 1994 with polycythemia. The patient's red blood cell volume was 33 ml/kg and bone marrow cytology was able to rule out other myeloproliferative diseases such as chronic myelogenous leukemia, essential thrombocytosis and myelofibrosis. The patient was diagnosed as having polycythemia vera. She had undergone only phlebotomy until 1999 when the thrombocytosis appeared, subsequent to which she was treated with oral hydroxyurea. However, in March 2006, she developed upper abdominal pain and was admitted to our hospital on March 14th, 2006. Computed tomography scan revealed thromboses in the portal and superior mesenteric veins. Anticoagulation therapy delivered intravenously via the superior mesenteric vein dramatically improved her symptoms and liver function. She is currently on anticoagulation therapy in our outpatient clinic.
Assuntos
Janus Quinase 2/genética , Oclusão Vascular Mesentérica/etiologia , Mutação Puntual , Policitemia Vera/complicações , Veia Porta , Trombose Venosa/etiologia , Feminino , Humanos , Veias Mesentéricas , Pessoa de Meia-Idade , Policitemia Vera/genéticaRESUMO
Amyotrophic lateral sclerosis (ALS) is a degenerative disease involving both upper and lower motor neurons and the pathogenesis of this disorder is still unknown. To date, few reports have suggested that motor neuron diseases may have a paraneoplastic origin. However, it is still under discussion whether ALS occurring in cancer patients is paraneoplastic. A 60-year-old man with rectal cancer (Stage IV) having multiple lung, liver and para-aortic lymph node metastases underwent anterior resection of the rectum as palliative surgery. He was referred to our hospital for adjuvant chemotherapy. Lung and lymph node metastases decreased after 2 courses of chemotherapy using CPT-11 and 5-FU/LV but liver metastases were enlarged, following up increase in CEA. Thereafter, he suffered from muscle weakness in hands, arms, and legs and results of neurophysiologic studies were compatible with primary lateral sclerosis (ALS). For second line chemotherapy, he was treated with low-dose CDDP/5-FU over 6 courses. As a result, the size the of metastatic lesions markedly reduced and CEA was decreased to the normal level. Although significant tumor reduction was observed, his neurological symptoms rapidly progressed. He died of aspiration pneumonia 8 months after onset of the disease. Autopsy revealed that his neuropathological findings were compatible with ALS, and it was thought to be the primary cause of death in the because of absence of cancer progression. In this case the neurological syndrome was not affected by cancer therapy. Thus our case does not support the hypothesis that ALS in associated with cancer and the relationship between both disorders remains uncertain.
Assuntos
Adenocarcinoma/secundário , Esclerose Lateral Amiotrófica/etiologia , Neoplasias do Colo/patologia , Adenocarcinoma/complicações , Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cisplatino/administração & dosagem , Neoplasias do Colo/complicações , Neoplasias do Colo/tratamento farmacológico , Esquema de Medicação , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: To determine the recommended dose (RD) of cis-diammine-glycolatoplatinum (nedaplatin) when given concurrently with 5-FU and high dose radiation therapy in the treatment of esophageal cancer. The purpose of the phase II trial is to determine efficacy and further define the side effect profile. METHODS: Twenty-six patients with clinical stage I to IVA squamous cell carcinoma of the esophagus were enrolled in a non-surgical treatment comprised of a fixed dose of fluorouracil (400 mg/m2 administered as continuous intravenous infusion on days 1-5 and days 8-12) plus escalating doses of nedaplatin (40 mg/m2 in level 1, 50 mg/m2 in level 2, or 60 mg/m2 in level 3 on days 1 and 8), repeated twice every 3 weeks with concurrent radiotherapy (60 Gy). RESULTS: Between July 1998 and February 2004, a total of 26 patients entered this trial, all of whom were considered evaluable for toxicity assessment. In phase I of the study, 12 patients were treated in sequential cohorts of three to six patients per dose level. The maximum tolerated dose was reached at level 3 with two grade 4 neutropenia and one grade 4 thrombocytopenia. Thus, the recommended dosing schedule is level 2. Of the 20 patients treated at the RD level 2, including 6 patients of the RD phase I portion, 8 out of 20 patients (40%) had grade 3-4 neutropenia, 5 patients (25.0%) had grade 3-4 thrombocytopenia, 4 patients (20.0%) had grade 3 anemia and 4 patients (20.0%) had grade 3-4 esophagitis. Other toxicities were relatively mild and usually of grade 2 or less. Objective responses were noted in the 26 patients (overall response rate, 88.5%) including 11 (42.3%) complete remissions. The 1- and 3-year survival rates were 65.1 and 37.2%, respectively, with a median survival time of 21.2 months. CONCLUSIONS: The combination of nedaplatin and 5-FU with radiation is a feasible regimen that shows promising antitumor activity with an acceptable safety profile in patients with esophageal cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/terapia , Radioterapia Adjuvante/métodos , Idoso , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Relação Dose-Resposta a Droga , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Esofagite/induzido quimicamente , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neutropenia/induzido quimicamente , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Radioterapia Adjuvante/efeitos adversos , Indução de Remissão , Índice de Gravidade de Doença , Taxa de Sobrevida , Trombocitopenia/induzido quimicamente , Resultado do TratamentoRESUMO
The patient was a 45-year-old male who had been diagnosed with pancytopenia in 1998 at another hospital, where he continued treatment for idiopathic thrombocytopenic purpura (ITP) as an outpatient. After atypical lymphocytes were detected in his peripheral blood, he was admitted to our hospital for further examination in April 2002. Tests results revealed the additional existence of pancytopenia, splenomegaly, bone marrow fibrosis and erythema nodosum, in addition to the findings of surface marker. Tartrate resistant acid phosphatase (TRAP) staining and scanning electron microscopy of peripheral blood lymphocytes indicated hairy cell leukemia. After administration of cladribine (0.09 mg/kg) for 7 days, complete remission was obtained, with bone marrow fibrosis and erythema nodosum also being completely improved.
Assuntos
Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Eritema Nodoso/tratamento farmacológico , Leucemia de Células Pilosas/tratamento farmacológico , Mielofibrose Primária/tratamento farmacológico , Esquema de Medicação , Eritema Nodoso/complicações , Humanos , Leucemia de Células Pilosas/patologia , Masculino , Pessoa de Meia-Idade , Pancitopenia/complicações , Mielofibrose Primária/complicações , Indução de Remissão , Esplenomegalia/complicaçõesRESUMO
Hepatic transdifferentiation of bone marrow cells has been previously demonstrated by intravenous administration of donor cells, which may recirculate to the liver after undergoing proliferation and differentiation in the recipient's bone marrow. In the present study, to elucidate which cellular components of human bone marrow more potently differentiate into hepatocytes, we fractionated human bone marrow cells into mesenchymal stem cells (MSCs), CD34+ cells, and non-MSCs/CD34- cells and examined them by directly xenografting to allylalcohol (AA)-treated rat liver. Hepatocyte-like cells, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), albumin (Alb), cytokeratin 19 (CK19), cytokeratin 18 (CK18), and asialoglycoprotein receptor (AGPR), and by reverse transcription-polymerase chain reaction (RT-PCR) for expression of AFP and Alb mRNA, were observed only in recipient livers with MSC fractions. Cell fusion was not likely involved since both human and rat chromosomes were independently identified by fluorescence in situ hybridization (FISH). The differentiation appeared to follow the process of hepatic ontogeny, reprogramming of gene expression in the genome of MSCs, as evidenced by expression of the AFP gene at an early stage and the albumin gene at a later stage. In conclusion, we have demonstrated that MSCs are the most potent component in hepatic differentiation, as revealed by directly xenografting into rat livers.