Biomedical subjects

A Sauerbrey

Publications and source records attributed to A Sauerbrey.

At least 37 records · Page 2Linked to original sources

PubMed1995

Messenger RNA expression of resistance factors and their correlation to the proliferative activity in childhood acute lymphoblastic leukemia.

In this report we analyzed the mRNA expression of the resistance-related enzymes DNA topoisomerase II (Topo II), thymidylate synthase (TS), glutathione S-transferase-pi (GST-pi) and glutathione peroxidase (GP) in childhood acute lymphoblastic leukemia (ALL) and their correlation to the proliferative activity, determined by Ki-67. RNA of blast cells from 54 children with untreated ALL were examined by dot blot hybridization. We found a significant positive correlation between Topo II and TS and cell proliferation. No significant correlation was detected between the mRNA expression of the glutathione-dependent enzymes GST-pi or GP and Ki-67. The results were substantiated by a semiquantitative RT-PCR-assay and by immunocytochemistry.

Cell Division↗

PubMed1994

Determination of DNA topoisomerase II in newly diagnosed childhood acute lymphoblastic leukemia by immunocytochemistry and RT-PCR.

The expression of DNA-topoisomerase II was analysed at the protein level in newly diagnosed cases of acute lymphoblastic leukemia (ALL) in children. Blast cells obtained from 81 children with untreated ALL were determined by means of immunocytochemistry. Of the ALL, 49 (60%) were positive for topoisomerase II and 32 (40%) negative. No significant correlation was found between the expression of topoisomerase II and the relapse rate or relapse-free intervals. These results were substantiated by determining the topoisomerase II mRNA expression in a collective of 21 patients by semiquantitative PCR. The PCR-assay and immunocytochemistry corresponded in 13 of 21 cases (62%).

Base Sequence↗

PubMed1994

Expression of metallothionein in initial and relapsed childhood acute lymphoblastic leukemia.

In a retrospective study we analyzed the expression of metallothionein (MT) in initial acute lymphoblastic leukemia (ALL) of 92 children and in relapsed ALL of 27 children using immunohistochemistry. MT expression was detectable in 33% of the patients with initial ALL and in 33% of the patients with relapsed ALL. No differences were seen concerning the intensity and the proportion of positively stained cells between initial and relapsed patients. The expression of MT was independent of clinical prognostic factors such as age, sex, immunological subtype, and initial blast cell count. Patients with initial ALL and MT expression tended to have a lower probability of disease-free survival compared with the MT-negative group. The relapsed patients with MT expression showed also a trend toward a shorter survival in comparison to the MT-negative group. However, the differences were not statistically significant. Thus, the results show that MT expression is not an important prognostic factor in the clinical drug resistance of childhood All.

Child↗

PubMed1994

P-glycoprotein and glutathione S-transferase pi in childhood acute lymphoblastic leukaemia.

Blast cells obtained from 104 children with untreated acute lymphoblastic leukaemia were analysed for the expression of P-glycoprotein (P-170) and glutathione S-transfer pi (GST-pi) using immunohistochemistry. Expression of P-170 was detected in 36 of 104 patients (35%) and increased GST-pi was seen in 52 patients (50%). Coexpression of both resistance proteins was observed in 22 leukaemias (21%), whereas no evidence of the resistance markers was found in 38 cases (37%). In patients with P-170-positive leukaemic cells, a significantly lower probability of remaining in first continuous complete remission (CCR) was observed when compared with patients with P-170-negative tumours (P < 0.05). However, only a trend for a more frequent expression of P-170 was found in the leukaemic cells of patients who experienced relapses (P = 0.099). Overexpression of GST-pi was correlated with a higher relapse rate (P = 0.001) and a lower probability of remaining in first CCR (P = 0.01). Expression of P-170 and GST-pi was independent of sex, FAB type, immunological subtype and initial blast cell count. The multivariate analysis indicated that only the expression of P-170 is an unfavourable prognostic factor for children with acute lymphoblastic leukaemia in addition to the prognostic clinical factors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

[The kinetics of vaccine antibodies against tetanus toxoid, diphtheria toxoid, measles virus, poliomyelitis virus and pneumococcus after allogeneic and autologous bone marrow transplantation and revaccination. 3: The kinetics of vaccine antibodies against tetanus toxoid and diphtheria toxoid after allogeneic and autologous bone marrow transplantation and combined revaccination against diphtheria and tetanus].

The 3rd part of the paper deals with the results of a combined revaccination against diphtheria and tetanus in a group of 25 children after allogeneic bone marrow transplantation (BMT) with and without graft versus host disease (GvHD) and after autologous transplantation. It can be shown that in the allogeneic transplanted groups with and without GvHD it is possible to build up a tetanus and diphtheria antitoxin titre in a safe protective cause by a 2nd basic immunisation consisting of 3 single vaccinations starting about 9 to 12 months later. For autologous transplanted children only 1 to 2 vaccinations at a later term than for the allogeneic transplanted children may possibly be sufficient.

Bone Marrow Transplantation↗

PubMed1989

[Acute lymphatic leukemia with pre-B-cell characteristics].

54 patients affected with acute lymphatic leukaemia (ALL) in the period from 1978-1984 were examined concerning the frequency of pre-B-ALL in comparison with other immunological subtypes of ALL. For this purpose the following markers were tested: 1. Cytoplasmatic IgM 2. Rosette formation with sheep erythrocytes 3. T-cell specific antigen 4. C-ALL antigen 5. Surface immunoglobulin By means of these markers the patients were divided into 5 immunological subtypes of ALL, viz. 1. Pre-B-ALL (16.6%) 2. O-ALL (37.1%) 3. C-ALL (27.9%) 4. T-ALL (16.6%) 5. B-ALL (1.8%) The immunological subtypes of ALL were compared by means of clinical parameters (age, initial leukocyte number, mediastinal tumor, initial CNS involvement). No difference could be detected between O-ALL, pre-B-ALL and C-ALL, whereas T-ALL showed a distinctly worse prognosis.

Adolescent↗

PubMed1989

Immunoreconstitution after human bone marrow transplantation.

Immunologic reconstitution was studied in 24 patients who underwent bone marrow transplantation, 17 allogenic and 7 autologous. The GVHD prophylaxis consisted of methotrexate and prednisone. The complete immune evaluation was to be carried out prior to transplantation at 1, 2, 3, 6, 9, 12 months after BMT and subsequently every 6 months up to 4 years. The investigated immunological parameters included total lymphocyte count, B-lymphocytes, T3-, T4-, T8-lymphocytes, T4/T8 ratio, natural killer cell activity, ADCC, lymphocyte blastogenic response and serum-IgG, -IgA, -IgM. Absolute lymphocyte count, B-lymphocytes, T3-lymphocytes recovered to normal levels after 6 months. T4-lymphocytes decreased significantly during the first 180 days posttransplant. T8-lymphocytes increased after 6 months to values higher than normal and the T4/T8 ratio decreased significantly and continued below 0.8 for 48 months. Patients without and with GVHD had low lymphocyte response to PHA and Con A for the first 6 months.

Adolescent↗

PubMedDate not supplied

[Results and experiences with a modified BFM protocol for treatment of recurrences in children with acute lymphoblastic leukemia in East German areas].

Between 1988 and 1990, 55 patients with first relapses of acute lymphoblastic leukemia (ALL) were treated with a modified BFM-protocol (ALL REZ I/88). The patients were divided according to time and site of relapse: relapses with bone marrow involvement up to 6 months after stopping front line therapy (group A), relapses with bone marrow involvement beyond 6 month after therapy (group B) and isolated extramedullary relapses at any time (group C). During therapy the patients received alternating courses of polychemotherapy including infusions of intermediate dose methotrexate (1 g/m2 in 36 hours). The maintenance treatment consisted of daily oral thioguanine and biweekly intravenous (IV) MTX. The overall second remission rate was 89% (group A: 90%, group B: 86%, group C: 93%) and the probability of event free survival (EFS) at 4 years is 0.28 +/- 0.13 (group A: 0.22 +/- 0.12, group B: 0.24 +/- 0.18, group C: 0.57 +/- 0.15). We conclude, that with the treatment regimen applied, long lasting second remission can be achieved in about one third of patients even after intensive front line therapy. The most unfavourable prognoses were seen in patients with early bone marrow relapses (group A).

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

[Expression and clinical significance of resistance proteins in initial acute lymphatic leukemia (ALL) in childhood].

In a retrospective study the expression of the resistance proteins P-170 glycoprotein (P-170), glutathione S-transferase pi (GST-pi), thymidylate-synthase (TS), dihydrofolate reductase (DHFR) and metallothionein (MT) was investigated in 111 patients with newly diagnosed acute lymphoblastic leukemia (ALL) using the streptavidin-biotin-peroxidase complex method. The expression of the resistance proteins was found in following frequency: P-170 in 39 (35%), GST-pi in 54 (49%), TS in 46 (42%), DHFR in 21 (20%) and MT in 30 (33%) cases of the investigated patients. Patients with overexpression of P-170 or GST-pi had a significant lower probability of remaining in continuous first remission (P < 0.05 for P-170 and P < 0.01 for GST-pi). The expression of TS and DHFR had no prognostic significance on the probability of first remission. Patients with MT-overexpression showed only a tendency for a lower probability of continuous first remission. Coexpression of P-170 and GST-pi was observed in leukemias of 22 patients (21%) and 38 patients (37%) showed no evidence for the expression of both markers. Combining P-170 and GST-pi improved the prognostic value. The expression of the resistance proteins was independent of age, sex, FAB-type, immunological subtype and of the initial peripheral blast cell count. The multivariate analysis indicated that only the expression of P-170 was an independent unfavorable prognostic factor for children with initial ALL. The reason for this was an minor correlation of P-170 and GST-pi (P = 0.01).

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

[Therapy-induced formation of ascites and pleural effusion during initial chemotherapy in a patient with non-Hodgkin's lymphoma. Ascites and pleural effusion during initial chemotherapy].

We report on a 16-year old boy with non-Hodgkin's lymphoma who acquired a therapy-induced ascites and pleural effusion during initial chemotherapy. This life-threatening condition could be controlled by intensive care measures including pleural tap and drainage. Chemotherapy could then be continued. The patient has been in continuous complete remission for 18 months.

Adolescent↗

PubMedDate not supplied

Protein expression profile of newly diagnosed acute lymphoblastic leukemia in children developing relapses.

The purpose of this investigation was to evaluate the expression profile of proteins involved in children with newly diagnosed acute lymphoblastic leukemia (ALL) children who are developing relapses. For this reason, the expressions of 10 proteins including proto-oncogene and tumor suppressor gene products, proliferative factors and resistance parameters in 104 initial cases of childhood ALL were analyzed and the proteins correlated with ALL patients who experienced relapses. Applying immunocytochemical assays, we found that 4 out of the 10 parameters revealed a relationship to developing relapses (Fisher's exact tests). These were the oncogene product Fos (p=0.002), the drug resistance proteins glutathione S-transferase (p=0.008) and P-glycoprotein (P-pg/MDR1) (p=0.07) and protein kinase C (p=0.01). By means of hierarchical cluster analysis, we were able to show that the patients could be separated according to their protein expression profile into clusters consisting of patients whose ALL relapsed later and of patients who did not show relapses in the future.

Child↗

PubMedDate not supplied

Analysis of cyclin D1 in de novo and relapsed childhood acute lymphoblastic leukemia.

In a retrospective analysis we investigated 59 children with de novo acute lymphoblastic leukemia (ALL) and 28 patients with relapsed ALL for the expression of cyclin D1 using RT-PCR. In addition, the relationships of cyclin D1 to the retinoblastoma tumor suppressor gene and the Ki-67-expression were analyzed. Cyclin D1-mRNA was detectable in 42 out of 58 patients with de novo ALL (72%) and in 26 out of 28 relapsed patients (93%). The blast cells of the relapsed patients contained significantly higher levels of cyclin D1-mRNA compared with the de novo group (p = 0.0007). The cyclin D1 expression was independent of the proliferative activity of the cells and inversely correlated to the expression of the retinoblastoma tumor suppressor gene (r = -0.27, p = 0.03). Prognostic considerations using Kaplan Meier estimates for the relapse-free interval showed that patients with high cyclin D1- mRNA levels had a poorer prognosis (p = 0.046).

Adolescent↗

PubMedDate not supplied

Proliferation and apoptosis in newly diagnosed and relapsed childhood acute lymphoblastic leukemia.

Children with acute lymphoblastic leukemia (ALL) who are treated with chemotherapy have remissions in more than 95% of the cases. However, 25% of the patients relapse and show resistance to chemotherapy. In this investigation we compared 25 newly diagnosed and 25 relapsed cases of ALL with respect to proliferation and apoptosis. Using immunocytochemistry and Western blotting, we determined the expression of cyclin A protein as a measure of the proliferative activity and the pro-apoptotic and anti-apoptotic factors, Fas, Fas ligand, caspase-3 and Bcl-2. Cyclin A expression was observed in 32% of the newly diagnosed cases and in 52% of the relapsed cases. Expression of Fas was found in 58% of the newly diagnosed and in only 27% of the relapsed samples. Of the newly diagnosed ALL, 88% expressed the Fas ligand while such expression was observed in 54% of the relapsed ALL. Sixty-four percent of the newly diagnosed cases expressed caspase-3 while only 48% of the relapsed samples did so. The anti-apoptotic factor, Bcl-2, was more frequently expressed in relapsed than in newly diagnosed cases. These data indicate that relapsed ALL more frequently exhibits high proliferative activity and reduced apoptosis than does newly diagnosed ALL.

Apoptosis↗

PubMedDate not supplied

Expression of Fas ligand in newly diagnosed childhood acute lymphoblastic leukemia.

Immunocytochemistry was used to analyze the expression of the Fas ligand (FasL) in sixty-four children with newly diagnosed acute lymphoblastic leukemia (ALL). FasL expression was detected in 55 of 64 children (86%). Children with newly diagnosed ALL and FasL expression exhibited longer relapse-free and overall survival times under chemotherapy than did patients who did not express the Fas ligand. These data suggest that Fas/FasL mediated signaling may play a general role in the cytotoxicity of anticancer drugs.

Blotting, Western↗

PubMedDate not supplied

p53 protein detected by two different antibodies: relationship to proliferation and prognosis in acute lymphoblastic leukemia.

The expression of p53 protein was examined in a series of 69 children with acute lymphoblastic leukemia with two different monoclonal antibodies (Mab 1801 and 240). p53 expression was detected with at least one antibody in 49 cases (71%), whereas only 19 cases (27%) were positive with both antibodies. Variability in the immunostaining could be observed depending on the antibody used. Mab 240 gave the highest rate of positive staining (58%), followed by 1801 with 39%. Positive staining with 1801 was significantly associated with decreased proliferation of tumor cells as measured by Ki-67 labelling, indicating that possibly the wild-type p53 protein is preferably stained with this antibody. However, neither of the two antibodies has prognostic value or is correlated with histopathological parameters.

Age Factors↗

PubMedDate not supplied

p53 expression and poor prognosis in childhood acute lymphoblastic leukemia.

Ninety-one children with untreated acute lymphoblastic leukemia (ALL) were analysed for expression of p53 using immunocytochemistry. p53 expression was found in 80% of the cases by Mab 421. Kaplan-Meier estimates show that patients with p53-positive leukemic cells had significantly shorter survival times under chemotherapy than those with p53-negative leukemic cells (p = 0.05, log-rank test). Statistical analysis revealed no correlation between p53 expression and patient's age, sex, immunotyping and initial peripheral blast cell count.

Antibodies, Monoclonal↗

PubMedDate not supplied

Thymidylate synthase in childhood acute non-lymphoblastic leukemia.

Childhood acute nonlymphoblastic leukemias (ANLL) of untreated patients were analysed for expression of thymidylate synthase (TS) using immunocytochemistry. Only patients who achieved a complete remission were entered into the study (n = 21 patients). Of the 21 ANLL, 11 showed an overexpression of TS. There exists a strong correlation between the expression of TS and the relapse rate (p = 0.029, Fisher's exact test). Only 3 out of 11 cases of TS-negative patients with ANLL relapsed whereas 8 out of 10 TS-positive cases experienced relapses. The relapse-free intervals of the patients with TS-positive leukemic cells were significantly shorter than those of patients with TS-negative leukemic cells (p = 0.025, log rank test). There was a trend for shorter overall survival times of patients with TS-positive leukemic cells compared with patients with TS-negative leukemic cells (p = 0.12).

Adolescent↗

PubMedDate not supplied

Dihydrofolate-reductase and thymidylate-synthase in childhood acute lymphoblastic leukemia.

The expression of thymidylate-synthase (TS) and dihydrofolate-reductase (DHFR) was analysed immunohistochemically in 110 initial and 28 relapsed childhood acute lymphoblastic leukemia (ALL). Relapse-rates were not significantly higher in initial ALL with overexpression of TS- and DHFR than in ALL without overexpression of the proteins. In addition, the disease-free survival was not different for patients with TS or DHFR-negative and TS- or DHFR-positive ALL. No differences were found in the overall survival times of patients with relapsed ALL and with or without expression of TS or DHFR. Of the initial ALL 42% showed TS-overexpression, whereas of the relapsed ALL 64% of the cases were TS-positive (p = 0.03). The corresponding values for DHFR were 20% and 32% (p = 0.18). The results demonstrate clearly that expression of the proteins TS and DHFR has no importance for the resistance of ALL although the proteins increase during treatment.

Adolescent↗