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Biomedical subjects

J Treuner

Publications and source records attributed to J Treuner.

At least 55 records · Page 3Linked to original sources

Metastatic rhabdomyosarcoma and histologically similar tumors in childhood: a retrospective European multi-center analysis.

This is a retrospective analysis of children with metastatic soft tissue sarcoma (STS) registered in the major European STS studies: the SIOP MMT 75, the German CWS 1981 and 1986 studies, the Italian STS study, and the United Kingdom Children's Cancer Study Group centres in Britain. One hundred forty-six patients out of 164 were evaluable in this analysis. The median age was 7 years (1-18) and the male/female ratio was 1.3:1. The median follow-up was 80 months (7-171). The most common site of the primary tumor was the extremity (28%), which correlated well with the high preponderance (39%) of the alveolar type of RMS (aRMS). There was no dominant combination of metastatic sites and the most common single organ with metastasis was the lung (41%). Since the therapy depended on the country and period in which the patient was treated, we did not analyse the outcome and therapy together. Complete remission was achieved in 50% of the cases. Those with aRMS had a good chance of achieving CR (61%) but the majority of these patients relapsed (78%). The median time needed to relapse was 243 days (53 days to 47 months) for all patients. Analysis of the site of the primary tumor showed that the CR rate was best in the GU non-BP site (62%) and worst in PM cases (35%). The overall survival and DFS rate were 18% and 15%, respectively. The GU non-BP patients had a DFS rate of 50%, while the rate for all other sites varied between 12% and 18%. A total of 24 patients remained in CCR. The majority of them had embryonal type of RMS and metastases in only one anatomic site. Our analysis indicates that the best chance of prolonged survival was in metastatic GU non-BP cases, patients with embryonal type RMS, and those with metastases in only one organ. To try to improve the treatment of metastatic STS, a prospective European cooperative study was started in 1989.

Adolescent↗

A phase I study of neuroblastoma with the anti-ganglioside GD2 antibody 14.G2a.

Nine patients with neuroblastoma stage IV were treated with the murine monoclonal antibody 14.G2a, directed against disialoganglioside GD2. The antibody was injected daily for 5-10 days and the total applied dosage ranged between 100 mg/m2 and 400 mg/m2. The peak serum levels of mAb 14.G2a ranged from 28 micrograms/ml to 61 micrograms/ml. Pharmacokinetic data obtained in three patients indicated that the serum elimination of mAb 14.G2a fits a two-compartment model, with an alpha-half-time (t1/2 alpha) between 0.66 h and 1.98 h and a beta-half-time (t1/2 beta) between 30.13 h and 53.33 h. All patients presented with a human anti-(mouse IgG) antibody response either during or shortly after therapy. Eight patients showed a continuous decrease in complement component C4 during therapy, as well as an initial decrease in C3c and an initial increase in C3a, all suggesting an activation of the complement cascade. Side-effects consisted of allergic reactions like pruritus, exanthema, urticaria and of severe pain, predominantly located in the abdomen and lower extremities, which required the use of continuous intravenous morphine. Four patients additionally developed a transient hypertension and one patient experienced a transient nephrotic syndrome. Three patients were treated in an adjuvant setting and are not evaluable for tumor response. Of the remaining six patients, two had a complete remission, two showed a partial remission, and two patients did not respond to treatment.

Antibodies, Anti-Idiotypic↗

Spindle cell rhabdomyosarcoma. A prognostically favorable variant of rhabdomyosarcoma.

Twenty-one cases of embryonal rhabdomyosarcoma, composed mainly of elongated spindle cells arranged in a fasciculated or storiform pattern, were retrieved from the files of the German-Italian Cooperative Soft Tissue Sarcoma Study. The term spindle cell rhabdomyosarcoma is proposed to designate this histotype. Spindle cell rhabdomyosarcoma predilected male patients (18 males, three females) and involved mostly the paratesticular area (12 cases) and the head and neck region (six cases). Histologically, all cases were characterized by a uniform proliferation of elongated spindle cells with eosinophilic and fibrillar cytoplasm mimicking smooth muscle fibers; immunocytochemical studies disclosed high expression of the muscle markers titin, desmin, and myoglobin. Clinical information was available in 17 cases; according to the Intergroup Rhabdomyosarcoma Study (IRS) grouping system, 13 were classified in group I, two in group II, and two in group III. Sixteen patients were well and alive 24 to 100 months after diagnosis; one patient died from disease progression 24 months after diagnosis. Analysis of our results determined that spindle cell rhabdomyosarcoma constitutes a rare variant of the embryonal form, showing a high degree of skeletal muscle differentiation and a low malignant potential; it should therefore be distinguished from classical forms of embryonal rhabdomyosarcoma.

Adolescent↗

Isotachophoretic determination of 2-5A phosphodiesterase.

Together with 2-5A synthetase and ribonuclease L, 2-5A phosphodiesterase belongs to the 2-5A system, which plays an important role in the action of interferon. Analytical capillary isotachophoresis was used for the determination of 2-5A phosphodiesterase activity. Enzyme assay was optimized using snake venom phosphodiesterase as a source of 2-5A phosphodiesterase activity. The 2-5A trimer core was used as a substrate. Enzyme activity was determined in time- and concentration-dependent reactions. In addition, 2-5A phosphodiesterase activity was determined in lysates of mononuclear blood cells.

Adenine Nucleotides↗

Synovial sarcoma in children and adolescents. A report from the Kiel Pediatric Tumor Registry.

Of 49 cases of synovial sarcoma, which represent 5.8% of all soft tissue sarcomas with confirmed diagnosis in the files of the Kiel Pediatric Tumor Registry (Kiel, Germany), 35 occurred in patients up to the age of 18 years. The lower extremities were the most common. The 35 cases included 21 biphasic and 14 monophasic fibrous synovial sarcomas. The different cell types constituting synovial sarcoma could be demonstrated by conventional light microscopic study, but more readily so by immunohistochemical study, particularly when antibodies against cytoskeletal components were applied. Aberrant antigen expression was noticed for the neural markers, protein S-100, and neuron-specific enolase. Moreover, four tumors were positive for Ki M7. Collagen type IV was found in all tumors tested. For the 20 patients enrolled in the Cooperative Soft Tissue Sarcoma Study of the German Society of Pediatric Oncology (GPO) the survival rate at 7 years is 63%. When five patients with initial recurrence are excluded, the survival rate is 72%. It is concluded that immunohistochemical study is useful in the diagnosis and differential diagnosis of synovial sarcomas despite certain limitations. Multimodality treatment approach has improved the overall prognosis. There is no relationship between histologic subtype and prognosis according to the classification scheme employed in this study.

Adolescent↗

Metaiodobenzylguanidine (mIBG) in treatment of 47 patients with neuroblastoma: results of the German Neuroblastoma Trial.

From 1984 to 1989, 47 children with relapsed, refractory, and/or metastasized neuroblastoma were treated with 131I-metaiodobenzylguanidine (mIBG) in several different treatment combinations. At initial diagnosis, 36 children had Evans stage IV and 11 stage III disease. In 16 of the 47 children, tumor recurred after complete remission prior to mIBG treatment, 26 of 47 progressed from residual or nonresponding tumor, and in 5 of 47 tumor progression during chemotherapy was observed. Altogether the children were treated with a total of 112 courses (range 1-6) with a mean dosage of 8.9 +/- 6.7 mCi/kg body weight/treatment course. Total dose was 283.2 +/- 203.7 mCi for stage III and 388.9 +/- 218.6 mCi for stage IV. Nine of 47 children reached a complete or a very good partial remission (CR and VGPR) from mIBG treatment alone, 13 of 47 achieved partial remission (PR). In an early analysis, 10 patients treated with mIBG in the neuroblastoma trial NB 85 of the German Society of Pediatric Oncology showed no significant difference in survival time compared with 30 conventionally treated children. However, the recent therapy series has been done with higher doses of mIBG, and during improved therapeutic scanning many more bone lesions could be detected than during earlier diagnostic scanning. We conclude that mIBG treatment has not yet fulfilled the expectations for it but still seems for certain indications to be a promising tool to treat neuroblastoma in the future. Moreover, the frontier of neuroblastoma detection is still advancing.

3-Iodobenzylguanidine↗

Prognostic factors in 951 nonmetastatic rhabdomyosarcoma in children: a report from the International Rhabdomyosarcoma Workshop.

A total of 951 newly diagnosed patients with nonmetastatic rhabdomyosarcoma (RMS) under 21 years of age from four different cooperative study groups were analyzed to identify the most important pretreatment tumor characteristics in predicting survival. The patient characteristics considered were tumor invasiveness (T), tumor size, status of locoregional lymph nodes, and primary site. The cooperative groups and studies analyzed were: SIOP [RMS-75 (1975-1984)], the Intergroup Rhabdomyosarcoma Study [IRS-II (1978-1982)], Federal Republic of Germany [CWS-81 (1981-1986)] and Italy [RMS-79 (1979-1986), each study involving a different therapeutic protocol. Patient characteristics identified as having a significant relationship to survival by univariate analysis were (favorable features given in brackets): tumor invasiveness [T1], tumor size [less than or equal to 5 cm], status of locoregional lymph nodes [clinically negative], and primary site [orbit and genitourinary non-bladder prostate (GU-non-BP) sites]. T2 tumors tended to have large size (greater than 5 cm), to be associated with positive nodes, and to have a different distribution by primary site than T1 tumors. A multivariate Cox regression analysis of the pooled data identified tumor invasiveness (T), primary site, and the interaction between T and primary site as significant predictive factors for survival. The prognosis of orbital tumors was consistently favorable regardless of T status, whereas the prognosis for "other sites" was consistently unfavorable. International cooperation in this study has permitted the identification of good and poor risk patient subgroups, permitting the focusing of therapeutic protocols to particular risk groups and setting the stage for common future therapeutic protocols for rare subgroups of patients.

Child↗

Application of an anti-myosin antibody for scintigraphic differential-diagnosis of infantile tumors.

Immunoscans with the Fab-fragment of the monoclonal anti-myosin antibody R11D10 labeled with 111In showed significant uptake in rhabdomyosarcoma, rhabdoid tumor, and primitive neuroectodermal tumor. The diagnosis of an antimyosin positive or negative tumor with the aid of the immunoscan was superior to clinical findings in combination with ultrasound and CT, and to histological diagnosis in tumor biopsies. In addition chemotherapeutically induced renal impairment can be diagnosed by diminished renal uptake of antimyosin.

Adolescent↗

Application of the murine anti-Gd-2 antibody 14.Gd-2a for diagnosis and therapy of neuroblastoma.

We have tested the sialoganglioside monoclonal antibody Gd-2a for scintigraphic diagnostic and for immunotherapy in children with neuroblastoma stage IV. We could confirm tumor sites with Gd-2a scans in 1/2 children. Doses of 20-60 mg/m2 were administered daily for 5-10 days. 2/2 children with multiple tumor sites showed significant tumor regression. Four children, treated preventively, are still in clinical remission. One child showed tumor progression despite Gd-2a treatment. Adverse effects included itching, rashes, and pain.

Adolescent↗

Neuroblastoma screening: arguments from retrospective analysis of three German neuroblastoma trials.

The justification for a neuroblastoma screening program has been discussed controversially. The analysis of 701 patients of the German neuroblastoma trials NB 79, 82, and 85 provides additional information on this subject. The basis of our investigation was the good prognosis of stage I and II patients (92% survival 5-10 years after diagnosis) compared with 66% in stage III and 11% in metastatic disease. The correlation of age and stage (p less than 0.0001), a median progression time of 14.6 months (range 3.4-33.5 mo) from localized to metastatic disease as observed in 18 patients, the high incidence of asymptomatic diseases in stages I (49%) and II (30%) patients and the cost-benefit estimation arguments in favor of a screening program. The key problem for the lab part is the lower incidence of abnormal catecholamine metabolite excretion in stage I and II patients. The origin of 89% of metastatic disease from intraabdominal sites suggests that ultrasonography may be of additional value.

Abdomen↗

Reduction of N-myc expression by antisense RNA is amplified by interferon: possible involvement of the 2-5A system.

Expression of myc-box genes can be reduced by Interferon (c-myc in Daudi cells) or Retinoic acid (N-myc in neuroblastoma cells). Interferon did not reduce N-myc expression in neuroblastoma cells. However, after transfection of the human neuroblastoma cell line LS with a vector, providing the Cadmium inducible expression of an antisense N-myc transcript, drastic reduction of N-myc RNA was achieved in these cells by incubation with Cadmium and Interferon. Treatment with Cadmium alone resulted in a comparably small reduction of N-myc transcripts in these cells. Interferon alone did not appreciably affect N-myc expression. Reduction of N-myc was accompanied with reduced cell proliferation and morphological differentiation. It is assumed that most of the inhibitory effects observed are mediated by the Interferon inducible 2-5A system.

2',5'-Oligoadenylate Synthetase↗

Vasoactive intestinal polypeptide (VIP) induces calcium mobilization in the human neuroblastoma cell line SK-N-SH.

Release of catecholamines, a Ca2(+)-dependent process, is the most useful biochemical marker in the diagnosis of neuroblastoma. Unfortunately, its stimulus is still unknown. We found that vasoactive intestinal polypeptide (VIP), in addition to acetylcholine and muscarine (but not nicotine), causes elevation of the cytoplasmic Ca2(+)-concentration in the highly differentiated human neuroblastoma cell line SK-N-SH, with or without the presence of extracellular Ca2+. Additionally, VIP was detected in SK-N-SH cells (0.65 ng/10(6) cells). Based on these observations and the fact that neuroblastoma is not innervated in vivo, we hypothesize that in this tumor VIP is responsible for Ca2(+)-dependent release of catecholamines in an autocrine or paracrine fashion.

Acetylcholine↗

In vitro and in vivo effect of interleukin-2 on the 2',5'-oligoadenylate synthetase activity of peripheral mononuclear blood cells.

The in vitro and in vivo influence of interleukin-2 (IL-2) on 2',5'-oligoadenylate (2-5A) synthetase activity and natural killer (NK) activity of peripheral mononuclear blood cells (PBMCs) was investigated. Incubation of PBMCs in vitro with IL-2 resulted in a considerable secretion of interferon-gamma (IFN-gamma) and in a significant elevation of 2-5A synthetase activity, as well as NK activity. Neutralizing monoclonal anti-IFN-gamma antibodies inhibited the elevation of 2-5A synthetase activity, but not the IL-2-induced augmentation of NK activity. Additionally, 2-5A synthetase and NK activity of PBMCs was measured in a child with neuroblastoma that was treated with recombinant IL-2 by continuous intravenous application. During the treatment, NK activity against the NK-sensitive cell line K 562 and against autologous tumor cells was not augmented. However, a significant increase of 2-5A synthetase activity in PBMCs was observed during IL-2 treatment, whereas there was no detectable serum level of IFN-gamma. We conclude that measuring 2-5A synthetase activity in patients treated with IL-2 may be helpful in monitoring the immunomodulatory effects of IL-2 on immune effector cells.

2',5'-Oligoadenylate Synthetase↗