RESUMO
The Wilms tumor locus on chromosome 11p13 has been mapped to a region defined by overlapping, tumor-specific deletions. Complementary DNA clones representing transcripts of 2.5 (WIT-1) and 3.5 kb (WIT-2) mapping to this region were isolated from a kidney complementary DNA library. Expression of WIT-1 and WIT-2 was restricted to kidney and spleen. RNase protection revealed divergent transcription of WIT-1 and WIT-2, originating from a DNA region of less than 600 bp. Both transcripts were present at high concentrations in fetal kidney and at much reduced amounts in 5-year-old and adult kidneys. Eleven of 12 Wilms tumors classified as histopathologically heterogeneous exhibited absent or reduced expression of WIT-2, whereas only 4 of 14 histopathologically homogeneous tumors showed reduced expression. These data demonstrate a molecular basis for the pathogenetic heterogeneity in Wilms tumorigenesis.
Assuntos
Genes do Tumor de Wilms/genética , Neoplasias Renais/genética , Tumor de Wilms/genética , Sequência de Bases , Northern Blotting , DNA/genética , Humanos , Dados de Sequência Molecular , Transcrição GênicaRESUMO
The aims of this study were to determine the maximum tolerated dose (MTD), toxicity and pharmacokinetics of oral temozolomide administered over 42 d in children with recurrent/refractory brain tumours. Cohorts of 3-6 patients were treated for 42 d, followed by a 7-d rest period for a maximum of 6 cycles. Patients were stratified as heavily pre-treated (HPT) and non-heavily pre-treated (NHPT). Starting doses were 50 mg/m2 (HPT) or 75 mg/m2 (NHPT). Out of 28 patients enrolled, 20 were evaluable for toxicity and 19 for pharmacokinetics. Three patients in the NHPT group developed grade 3/4 haematological toxicity, 2 experienced dose-limiting toxicity (thrombocytopenia) at 100 mg/m2, and 9/20 developed grade 3 lymphopenia. MTD in both strata was 85 mg/m2. Responses were observed in 4 patients: 2 complete responses (CR) in medulloblastoma and supratentorial primitive neuroectodermal tumours (PNET), and 2 partial responses (PR) in high-grade glioma, respectively. Overall cumulative exposure was at least 1.5 times higher than in the 5-d administration schedule. In conclusion, the recommended dose of temozolomide is 85 mg/m2 x 42 d. Dose-limiting toxicities are thrombocytopenia and lymphopenia. The observed response rate warrants phase II studies.
Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Recidiva Local de Neoplasia/tratamento farmacológico , Administração Oral , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/farmacocinética , Neoplasias Encefálicas/patologia , Criança , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/farmacocinética , Relação Dose-Resposta a Droga , Esquema de Medicação , Estudos de Viabilidade , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , TemozolomidaRESUMO
Mutations of the p53 tumor suppressor gene occur frequently in a variety of adult-onset tumors, including colon, breast, lung, and brain, yet are infrequently identified in pediatric malignancies. Wilms' tumor, a common solid tumor of childhood, can be associated with mutations of the WT1 gene. Alterations of the p53 gene have been shown to modulate the ability of WT1 to transactivate its targets. Although positive p53 immunostaining has been demonstrated in Wilms' tumors, the correlation to p53 gene mutations is not clear. We examined Wilms' tumor samples for p53 mutations utilizing polymerase chain reaction-single-strand conformation polymorphism analysis and single-strand DNA sequencing. Mutations in the coding region of the p53 gene were demonstrated in 2 of 21 (9.5%) Wilms' tumors. Each mutation yielded a substitution of amino acid residues. One mutation was located in exon 6 and the other in exon 7. Both mutations were found in tumors from patients with advanced stage disease. Focal anaplasia was demonstrated in one of these tumors. Our data suggest that although p53 mutations occur infrequently in Wilms' tumor, they may be associated with advanced disease.
Assuntos
Genes do Tumor de Wilms , Genes p53 , Neoplasias Renais/genética , Mutação Puntual , Tumor de Wilms/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Sequência de Bases , Criança , Pré-Escolar , Códon , Éxons , Feminino , Expressão Gênica , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumor de Wilms/tratamento farmacológico , Tumor de Wilms/patologiaRESUMO
Patients with the Denys-Drash syndrome (Wilms' tumor, genital anomalies, and nephropathy) have been demonstrated to carry de novo constitutional mutations in WT1, the Wilms' tumor gene at chromosome 11p13. We report three new cases, two carrying a previously described WT1 exon 9 mutation and one with a novel WT1 exon 8 mutation. However, unlike patients in previous reports, one of our three patients inherited the affected allele from his phenotypically unaffected father. This observation indicates that the WT1 exon 9 mutation affecting 394Arg demonstrated in over one-half of the patients with the Denys-Drash syndrome may exhibit incomplete penetrance. Consequently, familial studies in patients affected by this syndrome are recommended.
Assuntos
Cromossomos Humanos Par 11 , Genes do Tumor de Wilms/genética , Genitália Feminina/anormalidades , Genitália Masculina/anormalidades , Nefropatias/genética , Neoplasias Renais/genética , Mutação/genética , Tumor de Wilms/genética , Adolescente , Sequência de Aminoácidos , Criança , Éxons , Feminino , Humanos , Masculino , Dados de Sequência Molecular , SíndromeRESUMO
An analysis of over 1800 patients with Wilms' tumor revealed significantly higher birth weights than newborns in the general United States population. The highest birth weights were found not only in patients diagnosed with the Beckwith-Wiedemann syndrome (mean, 3.78 kg), as had been expected, but also in those with hemihypertrophy (3.80 kg) or perilobar nephrogenic rests (3.56 kg) in addition to their Wilms' tumor. The birth weights of Wilms' tumor patients with intralobar nephrogenic rests (3.43 on average kg) and of those without associated anomalies (3.45 kg) were slightly but still significantly higher on average than national birthweights (overall mean, 3.35 kg) adjusted for gender, race, and year of birth in each subgroup. Birth weights of children with aniridia and Wilms' tumor (2.99 kg) were lower than the national mean. Among more than 3000 patients with Wilms' tumor, heights and weights at diagnosis were significantly higher for the subgroups of patients with Beckwith-Wiedemann syndrome or hemihypertrophy, and height was lower for those with aniridia or characteristic genitourinary anomalies, when compared to other patients with Wilms' tumor. These data suggest prenatal effects of growth factors on the development of Wilms' tumors, or vice versa, and provide further epidemiological support for heterogeneity in the pathogenesis of Wilms' tumors associated with perilobar nephrogenic rests versus intralobar nephrogenic rests.
Assuntos
Síndrome de Beckwith-Wiedemann/complicações , Peso ao Nascer , Neoplasias Renais/complicações , Tumor de Wilms/complicações , Humanos , Hipertrofia/complicações , Rim/patologia , Neoplasias Renais/etiologia , Tumor de Wilms/etiologiaRESUMO
The molecular genetic events involved in the etiology of granulosa cell, Sertoli cell, and Leydig cell tumors are unknown. The expression of the Wilms' tumor suppressor gene WT1 in granulosa and Sertoli cells prompted us to analyze this gene for mutations in 11 granulosa cell tumors, three Leydig cell tumors, and one Sertoli/Leydig cell tumor. Although most of these tumors express WT1 mRNA, none harbors a WT1 mutation in the zinc finger domains where > 90% of WT1 mutations in sporadic Wilms' tumors have been found. In addition we were able to exclude tumor-specific loss of heterozygosity in 13 of 15 cases. Taken together these results suggest that the WT1 gene is unlikely to play an important role in the development of sex cord-stromal tumors.
Assuntos
Cromossomos Humanos Par 11 , DNA de Neoplasias/química , Éxons/genética , Regulação Neoplásica da Expressão Gênica/genética , Tumor de Células da Granulosa/genética , Tumor de Células de Leydig/genética , Neoplasias Ovarianas/genética , Tumor de Células de Sertoli/genética , Neoplasias Testiculares/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Criança , DNA de Neoplasias/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência MolecularRESUMO
Extrarenal Wilms' tumors are rare and have mainly been the subject of isolated case reports. This retrospective evaluation of 34 patients suggests a clinical course very similar to that of renal Wilms' tumor. While clinical presentation varies according to the extrarenal localization, investigations to determine the size of the primary tumor (T), regional lymph node involvement (N), and the occurrence of distant metastasis (M) are very similar, ie, chest x-ray, abdominal ultrasound (US), and computed axial tomographic (CAT) scan of the abdomen and chest. Stage grouping according to the pathologic TNM classification showed stage I in 30%, stage II in 10%, stage IIIa in 34%, stage IIIb in 23%, and stage IVa in 3%; four patients could not be staged. Evaluation of therapy and survival indicate the need for postoperative chemotherapy (CT) to all patients, while the same data suggest that the drugs used for renal Wilms' tumor are equally effective for extrarenal Wilms' tumor. Radiotherapy (RT) probably should be reserved for those patients with unresectable gross residual disease and for metastatic disease. The radiation dose used in the reviewed cases varied from 2,000 to 5,000 cGy. However, recent experience suggests that high doses are not justified in renal Wilms' tumor. The estimated overall 2-year survival of the 34 patients is 82% (95% confidence interval, 63% to 92%).
Assuntos
Tumor de Wilms/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Lactente , Masculino , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida , Tumor de Wilms/mortalidade , Tumor de Wilms/terapiaRESUMO
PURPOSE: A prospective study was performed to determine the incidence of acquired von Willebrand disease (vWD) in children with newly diagnosed Wilms' tumor. PATIENTS AND METHODS: Fifty consecutive children with newly diagnosed Wilms' tumor were evaluated. Detailed family and bleeding histories were obtained in all cases. Laboratory evaluation included measurement of the circulating platelet count, bleeding time (BT), factor VIII (FVIII) and von Willebrand factor (vWF) levels, and ristocetin cofactor (RCoF) activity. A vWF multimer analysis was obtained in all cases in which vWD was suspected. RESULTS: Four of 50 (8%) consecutive children with a diagnosis of Wilms' tumor were found to have acquired vWD. Laboratory findings indicated type III vWD in two patients and type I vWD in the other two. CONCLUSIONS: The incidence of acquired vWD in association with Wilms' tumor merits further study through a large prospective trial. Such a trial should include careful family and clinical bleeding histories plus measurement of a platelet count, BT, coagulant FVIII and vWF levels, RCoF activity, and vWF multimer analysis. The response to 1-desamino-8-D-arginine vasopressin (DDAVP) should be tested in all patients with Wilms' tumor and acquired vWD, including patients with a type III profile, before an invasive procedure is performed. Successful use of DDAVP may avoid exposure of affected patients to blood products.
Assuntos
Neoplasias Renais/complicações , Tumor de Wilms/complicações , Doenças de von Willebrand/complicações , Coagulação Sanguínea , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Neoplasias Renais/sangue , Masculino , Estudos Prospectivos , Tumor de Wilms/sangue , Doenças de von Willebrand/sangueRESUMO
Sixty-seven children with a bilateral Wilms' tumor (BWT) who were registered to the International Society of Pediatric Oncology (SIOP) nephroblastoma trial and studies 1, 2, and 5, conducted between 1971 and 1980, were analyzed. The overall 10-year survival was 64%. While most deaths due to tumor occurred within 3 years after diagnosis of bilateral disease, five patients died after 3 years (20%), three with synchronous and two with metachronous BWT. The survival rates for the 42 children with synchronous BWT (follow-up time, 6 1/2 to 14 years) and the 25 children with metachronous BWT (follow-up time, 5 to 13 years) were 69% and 56%, respectively. Due to an improvement in the synchronous group, overall survival improved over the years: 47%, 72%, and 70%, in SIOP 1, 2, and 5, respectively. Age at diagnosis and most advanced tumor stage affected prognosis. Children presenting a tumor manifestation before the age of 2 years had better prognosis than older children. This difference is significant in synchronous BWT. Prognosis for children with local stage 1 or 2 was better than for those with local stage 3. Median age at initial presentation in BWT was lower than in unilateral nephroblastoma and lower in metachronous BWT than in synchronous BWT. Young children presenting with unilateral nephroblastoma should have a careful follow-up of the contralateral kidney for at least the next 3 1/2 years, as most contralateral tumors will develop during this period.
Assuntos
Neoplasias Renais/mortalidade , Tumor de Wilms/mortalidade , Fatores Etários , Criança , Pré-Escolar , Europa (Continente) , Feminino , Seguimentos , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Masculino , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/terapia , Prognóstico , Estudos Retrospectivos , Tumor de Wilms/epidemiologia , Tumor de Wilms/patologia , Tumor de Wilms/terapiaRESUMO
PURPOSE: Children younger than 24 months with small (< 550 g), favorable histology (FH) Wilms tumors (WTs) were shown in a pilot study to have an excellent prognosis when treated with nephrectomy only. PATIENTS AND METHODS: A study of nephrectomy only for the treatment of selected children with FH WT was undertaken. Stringent stopping rules were designed to insure closure of the study if the true 2-year relapse-free survival rate was 90% or lower. RESULTS: Seventy-five previously untreated children younger than 24 months with stage I/FH WTs for which the surgical specimen weighed less than 550 g were treated with nephrectomy only. Three patients developed metachronous, contralateral WT 1.1, 1.4, and 2.3 years after nephrectomy, and eight patients relapsed 0.3 to 1.05 years after diagnosis (median, 0.4 years; mean, 0.51 years). The sites of relapse were lung (n = 5) and operative bed (n = 3). The 2-year disease-free (relapse and metachronous contralateral WT) survival rate was 86.5%. The 2-year survival rate is 100% with a median follow-up of 2.84 years. The 2-year disease-free survival rate (excluding metachronous contralateral WT) was 89.2%, and the 2-year cumulative risk of metachronous contralateral WT was 3.1%. CONCLUSION: Children younger than 24 months treated with nephrectomy only for a stage I/FH WT that weighed less than 550 g had a risk of relapse, including the development of metachronous contralateral WT, of 13.5% 2 years after diagnosis. All patients who experienced relapse on this trial are alive at this time. This approach will be re-evaluated in a clinical trial using a less conservative stopping rule.
Assuntos
Nefrectomia , Tumor de Wilms/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Projetos Piloto , Prognóstico , Tumor de Wilms/mortalidade , Tumor de Wilms/patologiaRESUMO
There is increasing interest in blood cell transplants (BCT) from normal donors as an alternative to BMT. Ten patients with relapsed or persistent leukemia after BMT received intensive cytotoxic conditioning followed by allogeneic BCT. Three BCT were from single-antigen mismatched donors; two of the corresponding recipients had rejected a BMT from the same donor. Two patients received BCT from a different donor (one matched, one single-antigen mismatched). The other six BCT were from the same, fully matched, bone marrow donors. Donors were given G-CSF to mobilize progenitor cells which were collected by a single 2-4 h leukapheresis. Methotrexate, CsA and folinic acid were used for GVHD prophylaxis for all transplants but CsA was discontinued sooner after BCT than after BMT. One patient died without engraftment having rejected a BMT from the same single-antigen mismatched donor 4 years previously. Nine patients had granulocyte recovery at a median of 14 days, up to 6 days faster than with their previous BMT. Platelet recovery was also 2-6 days faster than with BMT in four previously engrafting patients. Four patients died without platelet recovery after BCT within a year of BMT, three of treatment-related toxicity and one of relapse. Two patients developed grade II acute GVHD. Of six patients given BCT more than a year from BMT, four, all with acute leukemia, survive 7, 14, 29 and 29 months after BCT and one relapsed at 7 months. All four survivors developed chronic GVHD. These results indicate that BCT may be useful therapy for relapse occurring more than a year after BMT.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia/terapia , Adolescente , Adulto , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante HomólogoRESUMO
Eleven patients with high-risk hematologic malignancy received cryopreserved but otherwise unmanipulated blood cell transplants (BCT) from partially mismatched family members in whom progenitor cells had been mobilized by G-CSF. Donors were mismatched by up to one antigen in the GVH direction and up to three antigens in the rejection direction. Outcomes were compared with those of 22 patients receiving BCT from fully matched donors. Two mismatched patients died without engraftment on day 21 and 32. One had rejected bone marrow from the same donor, the other was mismatched by two antigens in the rejection direction and received the lowest dose of CD34+ cells. Median time to granulocyte engraftment was 21.5 (range 16-33) days for the mismatched group compared with 16 (11-28) days for the matched group (P = 0.01). No correlation was found between CD34+ cell dose and time to granulocyte or platelet recovery. In the mismatched and matched BCT groups respectively, the risk of grade II-IV acute graft-versus-host disease (GVHD) was 73% vs 28% (P = 0.001) and of chronic GVHD 100% vs 78% at 18 months (P = 0.01). The relationship of T cell dose to acute GVHD could only be evaluated in the matched group and no correlation was found. One of 11 mismatched patients and eight of 22 matched patients had relapse or persistent disease. Disease-free survival at 1 year was similar at 55% for mismatched and 50% for matched BCT. These results indicate that allogeneic BCT from partially mismatched family members is accompanied by a high incidence of GVHD but may result in comparable survival to BCT from fully matched donors.
Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Tipagem e Reações Cruzadas Sanguíneas , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo , Resultado do TratamentoRESUMO
Twenty-six patients with haematological malignancy received cryopreserved but otherwise unmanipulated blood cell transplants (BCT) from five- or six-antigen matched siblings in whom progenitor cells had been mobilized by G-CSF. Outcomes were compared with a historical control group of 26 BMT patients matched for age and disease status. Granulocyte counts recovered to 0.5 x 10(9)/l in a median of 16 days after BCT compared with 21.5 days after BMT (P = 0.0002). Platelet counts, unsupported for 3 days, reached 20 x 10(9)/l in a median of 14 days vs 20.5 days (P = 0.0003) after BCT compared with BMT in those patients who engrafted. In the BCT and BMT groups, respectively, the risk of grade II-IV acute GVHD was 37 vs 21% (P = 0.16) and of chronic GVHD at 1 year 53 vs 48% (P = 0.9). There was no significant difference in red cell transfusions but BCT patients required fewer platelet transfusions (median 3 vs 5, P = 0.015) and fewer days in hospital (20.5 vs 25, P = 0.02). These results indicate that allogeneic BCT from matched and partially mismatched family donors result in faster engraftment than BMT without a significant increase in GVHD. Allogeneic BCT may prove to be a more tolerable procedure than BMT for both donor and recipient and there are indications of improved cost-effectiveness.
Assuntos
Transplante de Medula Óssea , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Contagem de Células Sanguíneas , Transplante de Medula Óssea/efeitos adversos , Criança , Pré-Escolar , Família , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/sangue , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Lactente , Leucaférese , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Transplante HomólogoRESUMO
We have compared the outcomes of 87 patients with acute myelogenous leukemia (AML) and myelodysplasia (MDS) receiving matched sibling transplants with stem cells from peripheral blood (blood cell transplant, BCT) or bone marrow (BMT). In good risk patients (AML in CR1) granulocytes recovered to 0.5 x 10(9)/l a median of 14 days after BCT compared with 19 days after BMT (P < 0.0001). For patients with poor risk disease (AML beyond CR1 and MDS) corresponding figures were 16 vs 26 days (P < 0.0001). Platelet recovery to 20 x 10(9)/l was also faster after BCT (good risk 12 vs 20 days, P < 0.0001; poor risk 17 vs 22 days, P = 0.04). Red cell transfusions were unaffected by cell source, but BCT recipients required less platelet transfusions (good risk 1 vs 5, P = 0.002; poor risk 5 vs 11, P = 0.004). Blood cell transplants resulted in more chronic GVHD (86% vs 48%, P = 0.005) and a significantly higher proportion of recipients with KPS of 80% or less (48% vs 5%, P = 0.004). Disease-free survival at 4 years was 23% for both groups of poor risk patients but outcome in good risk patients was better after BCT (93% vs 62%, P = 0.047) related mainly to less relapse. While disease-free survival may be better after BCT than BMT for AML in CR1, quality of life may be relatively impaired.
Assuntos
Transplante de Medula Óssea/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Adolescente , Adulto , Transfusão de Componentes Sanguíneos , Doadores de Sangue , Criança , Pré-Escolar , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Recidiva , Relações entre Irmãos , Taxa de Sobrevida , Transplante HomólogoRESUMO
Each era with its own ideas and contributions will be evaluated at some point by future generations. The main objective of this historical overview of Wilms tumor has been to document some of the accomplishments made in the past two centuries. Knowing from where researchers, investigators, physicians, and other caregivers in this field have come will undoubtedly help to place today's achievements as mere markers between the past and the future.
Assuntos
Neoplasias Renais/história , Tumor de Wilms/história , Canadá , Pré-Escolar , Terapia Combinada , Europa (Continente) , História do Século XVIII , História do Século XIX , História do Século XX , Humanos , Lactente , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Estados Unidos , Tumor de Wilms/patologia , Tumor de Wilms/terapiaRESUMO
There has been a distinct evolution in the treatment philosophy for patients with BWT. Initial attempts at radical surgery have given way to the current use of preoperative chemotherapy to preserve as much kidney tissue as possible. With preoperative treatment, usually chemotherapy only, overall survival has become quite favorable in this group of patients, approaching 83% at 2 years. This has facilitated the use of parenchymal-sparing operations, with the potential advantage of decreasing the incidence of end-stage renal disease. The development of renal insufficiency in children with synchronous BWT nonetheless remains a concern. It is important that long-term survivors have systematic follow-up, with measurements of blood pressure, urine protein, serum creatinine, renal clearance, and renal size. Finally, despite the mentioned achievements, the management of children with synchronous BWT still needs standardization. The limited number of patients affected by BWT makes an international effort desirable to address this need.
Assuntos
Neoplasias Renais/terapia , Neoplasias Primárias Múltiplas/terapia , Tumor de Wilms/terapia , Diagnóstico por Imagem , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Lesões Pré-Cancerosas/epidemiologia , Fatores de Tempo , Tumor de Wilms/epidemiologia , Tumor de Wilms/genética , Tumor de Wilms/patologiaRESUMO
The national and international cooperative study groups have provided the scientific and administrative framework for the evaluation of various treatment regimens in patients with Wilms tumor. These have yielded excellent overall survival rates while identifying prognostic factors that have permitted modulation of therapy according to well-documented risk indices. Thus, they have demonstrated that treatments associated with important acute or long-term morbidities or both are not necessary for such patients as those with NWTS stage I or II, favorable histology Wilms tumor. It is now time to move beyond the traditional randomized prospective clinical trial method, which is not suitable to the attainment of remaining goals. Attempts to decrease the intensity of treatment even more in the future will be based on stratification of patients according to the presence or absence of one or more sensitive biologic prognostic factors. Such "markers," it is to be hoped, will make it possible to eliminate cardiotoxic and nephrotoxic drugs from the treatment of all but those at high risk of relapse.
Assuntos
Previsões , Neoplasias Renais/terapia , Projetos de Pesquisa/tendências , Tumor de Wilms/terapia , Núcleo Celular/patologia , Heterozigoto , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Prognóstico , Tumor de Wilms/genética , Tumor de Wilms/patologiaRESUMO
The study of Wilms tumor-predisposing congenital syndromes has led to the identification of one tumor-suppressor gene, WT1, and to the localization of WT2. Molecular genetic analyses of these and sporadic Wilms tumors have clarified the role of WT1 in Wilms tumor with aniridia, genitourinary malformations, and mental retardation (WAGR)-syndrome patients, but much remains unclear in the case of WT2 and the Beckwith-Wiedemann syndrome. Loci on chromosomes 16q and 1p have now been implicated in the progression of Wilms tumor and may serve as molecular prognostic markers. It is now clear that Wilms tumors are genetically heterogeneous and may be multigenic in origin. Molecular analyses can now be used for genetic counseling in some children and may become useful in individualizing therapy.
Assuntos
Genes do Tumor de Wilms , Mapeamento Cromossômico , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 11 , Regulação Neoplásica da Expressão Gênica/fisiologia , Genes Dominantes , Genes p53 , Humanos , MutaçãoRESUMO
The last few years have provided dramatic breakthroughs in understanding the genetic factors involved in Wilms' tumorigenesis and normal kidney development. The implications of these findings for the clinical management of children with Wilms' tumor are only now becoming apparent. Over 80% of patients with Wilms' tumor can be cured using contemporary multimodality therapy. As a consequence, the current NWTSG is attempting to intensify treatment for patients with poor prognostic features while decreasing therapy, and thereby adverse late effects, for patients with favorable prognosticators.
Assuntos
Genes do Tumor de Wilms/genética , Neoplasias Renais/genética , Tumor de Wilms/genética , Cromossomos Humanos Par 11/genética , Aconselhamento Genético , Humanos , Perda de Heterozigosidade , PrognósticoRESUMO
BACKGROUND: Platinum agents are frequently combined with ifosfamide. Mesna, originally coadministered to protect from ifosfamide side effects, might also react with the platinum agents in these combinations. METHODS: Malignant glioma cells were incubated with cisplatin, carboplatin and mesna. Cell numbers were measured by counting and by MTT-tests. RESULTS: In cell free solution mesna turned MTT to its blue farmazan product. Mesna's effect on cells were cell-line specific: It penetrated U87 cells without effect on growth, reduced cell numbers in C6 and T98G cells and did not alter U251 cells. The concentration of cisplatin killing 50% of the cells were 7 x 10(-7) in C6, 9.7 x 10(-6) in T98G, 1.2 x 10(-5) in U251 and 2.4 x 10(-4) in U87 cells. For the same effect, carboplatin required 3-10 times higher concentrations. Mesna protected all cell lines from the cytotoxicity of the platinum agents. CONCLUSION: Clinical studies should specify in detail, infusion schedules of mesna and platinum agents.