Biomedical subjects

A Zoubek

Publications and source records attributed to A Zoubek.

79 records · Page 5Linked to original sources

PubMedDate not supplied

[Minimal metastatic and minimal residual disease in patients with Ewing tumors].

At least 95% of Ewing tumors (ET) are characterized by an EWS-gene rearrangement with either FLI-1 or ERG and by extraordinary high MIC2/CD99 expression. Both features can be used for the specific identification of tumor cells, which might also be present in blood and bone marrow in minimal metastatic or minimal residual disease. We report the establishment of sensitive ET cell detection methods based on these characteristics. Preliminary results of 14 patients are given and two cases are reported in detail. 6/14 patients showed RT-PCR positivity in the bone marrow whereas in 8/14 patients ET cells could be detected by immunofluorescence. Only in 2 patients, one at diagnosis and one at relapse, tumor cells were detected in blood samples by RT-PCR. Peripheral blood stem cells of 5 patients showed no contamination with ET cells. The versatility of the immunocytochemical approach as compared to the RT-PCR analysis is discussed in order to explain the discrepancies between the results obtained with the two detection methods.

Adolescent↗

PubMedDate not supplied

[The EWS gene rearrangement in Ewing tumors: key to the disease].

The family of Ewing tumors (ET) is characterised by a unique gene rearrangement which is represented by a translocation t(11;22) (q24;q12) or a deletion del 22q12 in most cytogenetically analysable cases. The recent cloning of the underlying gene fusion provides the basis for the diagnostic detection of minimal amounts of residual tumor cells at resection margins, in blood and bone marrow. In addition, the very first steps in ET tumorigenesis can be studied on a functional basis. In this study, a variety of fusion products were identified with a sensitivity of 10(-6) by means of RT-PCR. In 20 of 22 ET, a gene rearrangement was identified which resulted in the substitution of the effector domain of one of the closely related DNA-binding oncogenes, FLI-1 or ERG, by the transactivating domain of a new gene, EWS. Presumably, the oncogene and consequently its target genes are activated by this type of translocation. If the EWS domain was replaced with a transcriptionally irrelevant domain by transfection of a recombinant gene into ET cells, competition with the endogenous chimeric oncogene-product for DNA-binding was observed resulting in a partial growth inhibition. Activation of FLI-1 has been previously shown to occur as a primary event in Friend virus induced mouse erythroleukemia. During progression of this disease, inactivating p53 mutations have been observed frequently. In contrast, such aberrations were found to be extremely rare in ET.

Adolescent↗

PubMedDate not supplied

[Venous thrombosis of cranial sinuses in asparaginase therapy. A case report].

Changes in the coagulation system due to steroids and asparaginase during treatment for acute lymphoblastic leukemia (ALL) are well known side effects and may cause bleeding or thrombosis. We report the case history of a 7-year old girl who developed thrombosis of the sinus sagittalis superior during ALL-treatment. Diagnosis was made by computed tomography and magnetic resonance imaging after the child became symptomatic with seizure. Until this event the girl had been treated already for two weeks with prednisone and E. coli-asparaginase (4 infusions). This medication caused distinct hypofibrinogenemia (Fibrinogen 53 mg/dl), prothrombin time expressed as percent of normal values of 58% was also pathological, activated partial thromboplastin time of 35 sec, antithrombin III 120% and thrombocyte count 178 G/l were in normal range. We were not successful in the attempt to adjust the imbalance in the coagulation system by transfusion of fresh frozen plasma (FFP)--seizure happened during FFP-infusion, fibrinogen blood level could be elevated only slightly. Our patient stayed consequently asymptomatic, the clinical recovery was confirmed radiologically.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Conventional vs. liposomal amphotericin B in immunosuppressed children.

Invasive fungal infections, mostly caused by Candida and Aspergillus species, are a major cause of early morbidity and mortality in immunocompromised children. The treatment of choice for systemic fungal infections is still the early intravenous administration of amphotericin B. However, conventional AMB therapy is often limited by severe side effects such as fever, chills, bronchospasm, and nephrotoxicity. In recent reports liposomal AMB (AmBisome) was shown to be effective in the treatment of severe systemic fungal infections. So far, clinical experience with AmBisome in children is still anecdotal and no comparative study is yet available. In the following we report on 11 immunosuppressed children who were treated with conventional or liposomal AMB for longer than 3 weeks.

Adolescent↗

PubMedDate not supplied

High-dose cyclophosphamide, adriamycin, and vincristine (HD-CAV) in children with recurrent solid tumor.

A dose-intensive regimen of cyclophosphamide (140 mg/kg over 2 days), doxorubicin (Adriamycin, 75 mg/m2 over 3 days), and vincristine (1 mg/m2 on days 1, 2, and 3 and 1.5 mg/m2 on day 9) was tested in 18 children and adolescents with poor-prognosis recurrent or refractory solid tumors. Nine were affected by neuroblastoma, 3 by Ewing's tumors, 2 by rhabdomyosarcoma, 2 by synovial sarcoma, 1 by hepatocellular carcinoma, and 1 by osteogenic sarcoma. All enrolled patients were heavily pretreated, including 2 patients after bone marrow transplantation. Forty courses were applied (median, 2). The overall response rate was 33% (2 complete remissions and 4 partial remissions). Responses were obtained in children with neuroblastoma, Ewing's tumors, and hepatocellular carcinoma. Myelosuppression [World Health Organization (WHO) grade IV after all courses] and cardiac toxicity (3 WHO grade I, 5 WHO grade III, and 3 WHO grade IV) were the main side effects. Nephrotoxicity and hepatoxicity were not observed. With further therapy consisting of surgery, radiotherapy, and high-dose chemotherapy [cisplatin, carboplatin/etoposide (VP16), or ifosfamide/VP16 with or without autologous stem cell reinfusion after conditioning with melphalan/VP16/carboplatin], 3 complete remissions and 5 very good partial remissions were obtained. Ten of 18 patients are alive after a median follow-up of 16 months.

Adolescent↗

PubMedDate not supplied

Successful carboxypeptidase G2 rescue in delayed methotrexate elimination due to renal failure.

We report on an 18.5-year-old woman with osteosarcoma and delayed methotrexate (MTX) elimination due to renal failure after high-dose MTX, in whom rescue with high doses of folinic acid caused intolerable side effects. In this life-threatening clinical situation, the patients was rescued by the administration of recombinant carboxypeptidase G2, a bacterial enzyme that rapidly hydrolyzes MTX into inactive metabolites. This is the first report on the successful clinical use of this alternative catabolic route for the elimination of MTX.

Adolescent↗

PubMedDate not supplied

Partial nephrectomy in well-responding stage I Wilms' tumors: report of three cases.

We report on 3 of 21 stage I Wilms' tumor patients with tumor volumes of 190, 890, and 1300 mL, respectively, who responded dramatically to preoperative chemotherapy according to the Austrian/Hungarian Wilms' Tumor Study 89 by tumor volume reductions to 20%, 23%, and 13%, respectively. Radical resection of the tumors with renal preservation was achieved in all patients. Postoperative studies did not show any functional deficit in the preserved kidney. The patients have been in complete remission for 26, 33, and 60 months, respectively. Our preliminary results indicate that tumor resection should be feasible in patients with good responding stage I Wilms' tumors.

Antineoplastic Combined Chemotherapy Protocols↗