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J Treuner

Publications and source records attributed to J Treuner.

At least 91 records · Page 5Linked to original sources
PubMed1988

MIBG-treatment in neuroblastoma; experiences of the Tübingen/Frankfurt group.

27 children with neuroblastoma were treated with 131I-Metaiodobenzylguanidine (MBIG). They were either refractory to conventional therapy or experienced relapse after initially successful treatment. 7 children revealed stage IV and 20 stage III at the beginning of MIBG-treatment. MIBG was administered by infusion lasting from 30 min to 30 hrs. In most children the dose was split into two portions each infused over a period of 4 hrs with a 24 hrs interval between. Courses were repeated up to 6 times and maximum activity given to one patient cumulatively was 38,221 MBq. 24 patients were evaluable for analysis of results. In 4 children (16.7%) a CR was observed, in 10 (41.7%) a PR, in 5 (20.8%) a disease stabilization and 5 were nonresponders. The 4 CR-patients were initially stage IV. 3 of them were treated in addition by bone marrow transplantation (bmt), one by further chemotherapy. 3 died of a relapse, 1 of complications from bmt. 5 of the 10 PR-patients died of tumor progression, 3 achieved a CR by additional chemotherapy, 1 a PR by bmt and 1 stays in PR without further measures. 2 of the 5 children with a disease stabilization were the first treated patients to whom a fairly low dose was given. In 3 of the 5 nonresponders no uptake of MIBG was observed; they died from tumor progression. 1 of the 2 nonresponders with uptake died of graft-versus-host disease after bmt, 1 other also of tumor progression. Duration of remission was between 1 and 12 months and depended upon uptake and dose of MIBG, interval between administrations and individual tumor behaviour. Side effects were seen as marked bone marrow depression; this was reversible in any case and we did not loose a patient due to MIBG-induced leuko- or thrombopenia. In cases of severely ill children we observed a very fast and dramatical amelioration in clinical conditions. With this method even in neuroblastoma relapse and in nonresponders complete remissions are achievable. Important is the intensification of the therapeutical effect by additional chemotherapy or in combination with bmt. For a definitive evaluation further investigations are necessary to optimize therapeutic strategies.

3-Iodobenzylguanidine↗
PubMed1987

Stability and pharmacokinetics of m-[131I]iodobenzylguanidine in patients.

A pharmacokinetic study was done to elucidate the body distribution, elimination, and metabolism of m-[131I]iodobenzylguanidine (m-[131I]IBG). For this purpose, an analytical method using solid phase extraction columns was developed. m-[131I]IBG was administered as an i.v. infusion according to different schedules with doses of 7,055 to 13,580 MBq/m2. At the start of the infusion m-[131I]IBG accounted for 93.0 +/- 2.3% (SD; n = 10) of the total radioactivity. At the end of the infusion m-[131I]IBG accounted for 88.0 +/- 7.4%. The non-m-IBG-bound radioactivity was predominantly 131I. The pharmacokinetic parameters (n = 7) are adequately described by a three compartment model. The parameters for m-[131I]IBG were determined with a mean terminal half-life of 37.0 h, a volume of distribution of 307 liters/m2, and an area under the curve value of 1091 kBq x h/ml. The total body clearance was 189 ml/min/m2. The values for 131I showed a terminal half-life of 71.6 h, a volume of distribution of 190 liters/m2, and an area under the curve value of 1537 kBq x h/ml. The total body clearance was 70 ml/min/m2. The selectivity of the m-[131I]IBG treatment might be improved by a reduction of 131I in the infusion fluid and further investigations are warranted.

3-Iodobenzylguanidine↗
PubMed1987

Metaiodobenzylguanidine (MIBG) labeled with 123I/131I in neuroblastoma diagnosis and follow-up treatment with a review of the diagnostic results of the International Workshop of Pediatric Oncology held in Rome, September 1986.

Our experience in scintigraphic diagnosis using 123I/131I-metaiodobenzylguanidine (MIBG) on 37 children with neuroblastomas stage III-IV is reported and discussed, together with the results obtained by other authors on MIBG diagnosis at the International Workshop of Pediatric Oncology held in Rome in September 1986. In our own investigation, 49 examinations were undertaken with 123I-MIBG and 66 with 131I-MIBG partly under therapy conditions with high-activity doses of 131I-MIBG. There were 29 neuroblastomas, 3 ganglioneuromas, and 3 ganglioneuroblastomas. The localization of all primary tumors was over 90%; for neuroblastomas with a high level of catecholamine excretion, over 95%. The specificity was about 100%. The sensitivity with respect to tumor relapse and all localization of metastasis and bone-marrow tumor infiltration in the follow-up-phase approaches was 70% during or after therapy. What emerges from the experience of most investigators is that 123I-MIBG is the agent best suited to detect tumor relapse and metastasis, especially in the bone marrow. MIBG examinations are of great value in follow-up studies for detecting tumor relapse and bone marrow infiltrations, especially before the onset of clinical symptoms and other indications.

3-Iodobenzylguanidine↗
PubMed1987

Treatment of neuroblastoma with metaiodobenzylguanidine: results and side effects.

Between April 1984 and December 1985 we treated ten children suffering from neuroblastoma in a total of 25 metaiodobenzylguanidine (MIBG) courses. Five had had a relapse of neuroblastoma stage III or IV, three had never achieved a remission in spite of intensive chemotherapy, and two were treated with an unstable remission. The children were each administered from 1 to 5 courses with a dosage per course of between 1,295 and 9,065 MBq. The sum of the single doses during the whole course of therapy ranged between 3,145 and 21,904 MBq per child. Five of five children suffering from bone pain and fever became free of complaints during the first three treatment days. Six of eight children with manifest tumor at onset of therapy responded well to the treatment: response extended from transitory decrease in elevated catecholamine levels in serum and urine to complete disappearance of large abdominal tumor masses. We also observed a decrease in bone marrow involvement and a stabilization of osteolytic lesions. Seven of these eight children died in spite of a good response from 55 to 350 days after the first MIBG treatment course. The only side effect we witnessed was a reversible bone marrow depression. In three children we combined the MIBG therapy with bone marrow transplantation.

3-Iodobenzylguanidine↗
PubMed1987

Methods for the determination of the interferon-induced enzyme 2'-5' oligoadenylate synthetase in mononuclear blood cells.

The determination of 2'-5'-oligoadenylate synthetase in peripheral blood mononuclear cells is used as a biological response parameter during therapy with interferon and in the diagnosis of diseases related to the interferon system. In this communication, some general aspects concerning the preparation of 2'-5'-oligoadenylate synthetase from peripheral blood mononuclear cells and the incubation conditions of the 2'-5'-oligoadenylate synthetase reaction are reported. Four analytical procedures for the determination of the products formed during the 2'-5'-oligoadenylate synthetase reaction were comparatively investigated and the advantages and limitations of the assays are discussed. As an example of possible clinical application, the levels of 2'-5'-oligoadenylate synthetase were determined in the mononuclear cell fraction of peripheral blood from healthy persons as well as from children with chronic myelogenous leukaemia.

2',5'-Oligoadenylate Synthetase↗
PubMed1987

Kinetics of restoration of interferon production after bone marrow transplantation in man.

Peripheral blood mononuclear cells (PBMC) from 21 patients after bone marrow transplantation (BMT) were studied for their capacity to produce interferon (IFN) in vitro. The basal and IFN-stimulated 2-5 A synthetase activity was also investigated as a marker of the cells' ability to respond to exogenous IFN. All but one patients received cyclosporin A as a prophylaxis against graft-versus-host disease (GVHD). GVHD was diagnosed in three patients. IFN production in response to stimulation with phytohemagglutinin or poly I:C was not detectable in most patients without GVHD until 7 months after grafting. However, in a proportion of recipients without GVHD, studied early after BMT, transient normal IFN production was observed. In contrast to patients without GVHD, PBMC from patients with GVHD produced stable high levels of IFN when stimulated in vitro. The impairment of IFN production did not correlate with conditioning regimens, infection, plasma cyclosporin levels or the lymphocytes' blastogenic response to the mitogens. Addition of interleukin-2 (IL-2) to culture medium of fresh unresponsive PBMC restored only partially the defective IFN production. Similarly, T-cell lines propagated in IL-2 conditioned medium, from unresponsive PBMC, produced low levels of IFN gamma when stimulated with PHA. The basal activity of 2-5 A synthetase in PBMC from patients without GVHD could not be stimulated, during the first 3 months after BMT, by the cultivation of cells with IFN alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

2',5'-Oligoadenylate Synthetase↗
PubMed1986

Cellular differentiation and prognosis in embryonal rhabdomyosarcoma. A report from the Cooperative Soft Tissue Sarcoma Study 1981 (CWS 81).

Sixty-four cases of embryonal rhabdomyosarcoma (eRMS) were investigated for cellular differentiation by light microscopy. Of these 64 cases 20 were studied by means of immunohistochemistry. Histologically, three subgroups could be distinguished: primitive (less than 10% rhabdomyoblasts), intermediate (10-50% rhabdomyoblasts) and well differentiated (greater than 50% rhabdomyoblasts) eRMS. Vimentin-positive cells predominated in the primitive eRMS. Intermediate eRMS showed large proportions of desmin-positive cells but vimentin containing cells were also numerous. Myoglobin could only be demonstrated in well differentiated eRMS. Primitive and well differentiated eRMS mainly occurred in the head and neck area, whereas intermediate eRMS were predominantly located in the abdomen. Stage III and IV tumours predominated in cases of primitive eRMS, whereas lower stages were noted in cases of intermediate and well differentiated eRMS. Response to chemotherapy, evaluated after seven weeks of treatment, was achieved in 10/15 (66%) cases of primitive, in 16/19 (84%) cases of intermediate and 5/5 cases of well differentiated eRMS. It is concluded from the current study that the three subgroups of eRMS differ not only by cytological differentiation but also by site of predilection, stage at time of diagnosis and response to chemotherapy.

Abdominal Neoplasms↗
PubMed1986

Clinical experiences in the treatment of neuroblastoma with 131I-metaiodobenzylguanidine.

Treatment of neuroblastoma is an unsolved problem of pediatric oncology. In spite of highly intensified chemotherapy, the long-term survival rate of children with a metastatic neuroblastoma is below 10%. We therefore used 131I-metaiodobenzylguanidine (MIBG) for the first time to treat children with a neuroblastoma in relapse or primary unresponsiveness to chemotherapy. We had previously demonstrated that MIBG is useful for the scintigraphic imaging of neuroblastoma lesions and had investigated the cytotoxicity and uptake of MIBG in various neuroblastoma cell lines. We treated 6 children with neuroblastoma in a total of 19 courses. Three of the children suffered from a relapse of neuroblastoma; 3 had never gained a remission. Four of the 6 children lost their bone pain and fever during the first 3 days. In 5 of the 6 children the solid tumor as well as the bone marrow infiltration responded to MIBG treatment, with responses ranging from transitory decrease of the tumor mass to complete disappearance of abdominal tumors. We also witnessed a stabilization of osteolytic lesions, a decrease in elevated serum catecholamines, and a decrease in bone marrow infiltration. Five of the 6 children died of tumor progression 55-249 days after the first MIBG treatment.

3-Iodobenzylguanidine↗
PubMed1985

The role of reactive oxygen compounds derived from 6-hydroxydopamine for bone marrow purging from neuroblastoma cells.

6-Hydroxydopamine(6-OHDA), a specific neurotoxin against sympathetic nerve cells, is a drug already used for purging of bone marrow from neuroblastoma cells before autologous bone marrow transplantation. However, we could not detect significant differences in the toxicity of 6-OHDA against neuroblastoma and other tumor cells under the purging conditions clinically used. In contrast, bone marrow stem cells were much more resistant. The unspecific toxic effect of 6-OHDA is caused by H2O2 or H2O2-derived products which are generated by auto-oxidation in the incubation medium before a significant amount of 6-OHDA is taken up by the cells. Withdrawal of oxygen during the incubation period and subsequent incubation with an oxygen containing medium led to a more specific destruction of neuroblastoma cells which can take up 6-OHDA selectively.

Ascorbic Acid↗
PubMed1985

Soft-tissue sarcomas in childhood. A study of 262 cases including 169 cases of rhabdomyosarcoma.

Although numerous investigations of soft-tissue sarcomas of childhood have been done, there are still many unsolved problems in the diagnosis, histogenesis, and biological behaviour of such tumours. In the present study, the soft-tissue sarcomas collected at the Paediatric Tumour Registry in Kiel were investigated. There was a total of 262 cases, including 169 (64.5%) in which a definite diagnosis of rhabdomyosarcoma had been made. An analysis of the age distribution showed that rhabdomyosarcoma is more than three times as frequent as non-rhabdomyosarcomatous soft-tissue tumours in the first quinquennium. Rhabdomyosarcoma exhibited male predominance (male-to-female ratio 1.45:1), whereas non-rhabdomyosarcomatous tumours showed an approximately equal sex distribution. Among the cases of rhabdomyosarcoma, the embryonal type clearly predominated (approx. 70%); the alveolar type was less common (approx. 20%). Correlation of histology with prognosis revealed that even tumours showing tiny foci with an alveolar pattern in otherwise solid, undifferentiated rhabdomyosarcoma, must be classified as alveolar rhabdomyosarcoma. Cases of alveolar rhabdomyosarcoma showed a higher incidence of local recurrence, lymph node metastasis, distant metastatic spread, and death, than did cases of embryonal rhabdomyosarcoma. It is concluded that "cytological differentiation" does not improve the prognosis of rhabdomyosarcoma.

Adolescent↗
PubMed1985

The combined effect of interferon-beta and cytostatic drugs on human tumor cell lines in vitro.

Three human tumor cell lines (one osteosarcoma and two neuroblastoma lines) were assessed for combined interferon-beta (IFN-beta)/chemotherapeutic drug antigrowth effect under in vitro conditions. Two different methods to measure this effect were used: colony formation in soft agar and counting of cells growing as monolayers. The cells were incubated with a chemotherapeutic drug (adriamycin, dacarbazine, actinomycin D, cis-platinum, methotrexate, VP-16-213, or vincristine) at relevant concentrations for 1 h, washed twice, and incubated with IFN-beta in concentrations ranging from 100 to 1000 IU for continuous exposure. All combinations resulted in an additive or synergistic combination effect with one exception: methotrexate/IFN-beta in the monolayer method after 1 week, a combination which was additive after 3 weeks however. The combinations VP-16-213/IFN-beta and cis-platinum/IFN-beta produced the most pronounced synergistic effects. A statistical evaluation of the null hypothesis for additivity was done. These results provide a rationale for designing clinical studies combining IFN-beta with current chemotherapeutic drugs.

Antineoplastic Agents↗
PubMed1985

Specific uptake of m-[125I]iodobenzylguanidine in the human neuroblastoma cell line SK-N-SH.

The uptake of m-[125I]iodobenzylguanidine (mIBG), a compound structurally analogous to the antihypertensive drug guanethidine, was examined in various human cell lines. Of three neuroblastoma lines, SK-N-LO, IMR-32, and SK-N-SH, only the last showed specific uptake of the compound. In contrast, only a nonspecific uptake could be demonstrated for the other neuroblastoma lines, as well as for an osteogenic sarcoma line (SAOS-2) and a melanoma line (IgR 3). Based on analyses of uptake characteristics from Lineweaver-Burk plots it is evident that two different transport mechanisms are responsible for mIBG uptake into SK-N-SH cells: a nonspecific diffusion mechanism, and a specific, active uptake system. The latter was dramatically reduced at 4 degrees compared to 37 degrees, as well as in the presence of ouabain or the absence of oxygen. A competitive inhibition of the transport of mIBG by norepinephrine was observed. When drug-treated SK-N-SH cells were incubated in fresh medium, 20 to 30% of mIBG was still retained in the SK-N-SH cells 24 h after the end of incubation with mIBG, whereas no mIBG was detectable in SK-N-LO cells already after 1 h.

3-Iodobenzylguanidine↗
PubMed1985

[Use of 131I-meta-iodobenzylguanidine in pediatric oncology].

The detection of specific trapping of MIBG by neuroblastoma cells is of great importance for the diagnosis and management of neuroblastoma in childhood. The specificity and sensitivity of the test has been demonstrated by Kimmig and Feine in a multi-center study. Moreover, MIBG might be used in the therapy of neuroblastoma. The first therapeutic cases allow slight optimism. There remain however still a number of questions to be answered. In vitro investigations of uptake kinetics and cytotoxicity of MIBG performed by our group provided valuable information for clinical investigations.

3-Iodobenzylguanidine↗