PubMed Health⌕ Search

Biomedical subjects

H Juergens

Publications and source records attributed to H Juergens.

At least 19 recordsLinked to original sources
PubMed2006

CD28 co-stimulation via tumour-specific chimaeric receptors induces an incomplete activation response in Epstein-Barr virus-specific effector memory T cells.

Expression of tumour antigen-specific chimaeric receptors in T lymphocytes can redirect their effector functions towards tumour cells. Integration of the signalling domains of the co-stimulatory molecule CD28 into chRec enhances antigen-specific proliferation of polyclonal human T cell populations. While CD28 plays an essential role in the priming of naive CD4(+) T cells, its contribution to effector memory T cell responses is controversial. We compared the function of the chRec with and without the CD28 co-stimulatory domain, expressing it in peripheral blood T cells or Epstein-Barr virus (EBV)-specific T cell lines. The chimaeric T cell receptors contain an extracellular single-chain antibody domain, to give specificity against the tumour ganglioside antigen G(D2). The transduced cytotoxic T lymphocytes (CTL) maintained their specificity for autologous EBV targets and their capacity to proliferate after stimulation with EBV-infected B cells. Intracellular cytokine staining demonstrated efficient and comparable antigen-specific interferon (IFN)-gamma secretion by CTL following engagement of both the native and the chimaeric receptor, independent of chimaeric CD28 signalling. Furthermore, tumour targets were lysed in an antigen-specific manner by both chRec. However, while antigen engagement by CD28 zeta chRec efficiently induced expansion of polyclonal peripheral blood lymphocytes in an antigen-dependent manner, CD28 signalling did not induce proliferation of EBV-CTL in response to antigen-expressing tumour cells. Thus, the co-stimulatory requirement for the efficient activation response of antigen-specific memory cells cannot be mimicked simply by combining CD28 and zeta signalling. The full potential of this highly cytolytic T cell population for adoptive immunotherapy of cancer requires further exploration of their co-stimulatory requirements.

Antigens, Neoplasm↗
PubMed2005

Esomeprazole 20 mg vs. pantoprazole 20 mg for maintenance therapy of healed erosive oesophagitis: results from the EXPO study.

BACKGROUND: Following initial healing of erosive oesophagitis, most patients require maintenance therapy to prevent relapse. AIM: To compare endoscopic and symptomatic remission rates over 6 months' maintenance therapy with esomeprazole or pantoprazole (both 20 mg once daily) in patients with healed erosive oesophagitis. METHODS: Patients with symptoms of gastro-oesophageal reflux disease and endoscopically confirmed erosive oesophagitis at baseline were randomized to receive esomeprazole 40 mg or pantoprazole 40 mg for up to 8 weeks. Patients with healed erosive oesophagitis and free of moderate/severe heartburn and acid regurgitation at 4 weeks or, if necessary, 8 weeks entered the 6-month maintenance therapy phase of the study. RESULTS: A total of 2766 patients (63% men; mean age 50 years) received esomeprazole 20 mg (n = 1377) or pantoprazole 20 mg (n = 1389) and comprised the intention-to-treat population. Following 6 months of treatment, the proportion of patients in endoscopic and symptomatic remission was significantly greater for those receiving esomeprazole 20 mg (87.0%) than pantoprazole 20 mg (74.9%, log-rank test P < 0.0001). Esomeprazole 20 mg produced a higher proportion of patients free of moderate to severe gastro-oesophageal reflux disease symptoms and fewer discontinuations because of symptoms than pantoprazole 20 mg (92.2% vs. 88.5%, P < 0.001). CONCLUSIONS: Esomeprazole 20 mg is more effective than pantoprazole 20 mg for maintenance therapy following initial healing of erosive oesophagitis and relief of gastro-oesophageal reflux disease symptoms.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

A randomized comparative study of esomeprazole 40 mg versus pantoprazole 40 mg for healing erosive oesophagitis: the EXPO study.

AIM: To assess the efficacy of the 8-week therapy with esomeprazole 40 mg vs. pantoprazole 40 mg for healing erosive oesophagitis (EE) as part of a management study. METHODS: Patients had a history of gastro-oesophageal reflux disease symptoms (> or =6 months) and had suffered heartburn on at least 4 of the 7 days preceding enrollment. Endoscopies were performed to grade EE severity using the Los Angeles (LA) classification system at baseline, 4 and 8 weeks (if unhealed at 4 weeks). Heartburn severity was recorded by patients on diary cards. The primary end point was healing of EE by week 8 of treatment. RESULTS: Of 3170 patients randomized, the intent-to-treat population consisted of 3151 patients (63% male, mean age: 50.6 years, 27% Helicobacter pylori-positive). Esomeprazole 40 mg healed a significantly greater proportion of EE patients than pantoprazole 40 mg at both 4 weeks (life table estimates: esomeprazole 81%, pantoprazole 75%, P < 0.001) and 8 weeks (life table estimates: esomeprazole 96%, pantoprazole 92%, P < 0.001). The median time to reach sustained heartburn resolution was 6 days in patients receiving esomeprazole and 8 days with pantoprazole (P < 0.001). CONCLUSION: Esomeprazole 40 mg is more effective than pantoprazole 40 mg for healing EE and providing resolution of associated heartburn.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

High-dose therapy for patients with primary multifocal and early relapsed Ewing's tumors: results of two consecutive regimens assessing the role of total-body irradiation.

PURPOSE: Risk stratification of metastatic and relapsed Ewing's tumors (ETs) has been a matter of debate during the last decade. Patients with bone or bone marrow metastases or early or multiple relapses constitute the worst risk group in ET and have a poorer prognosis than patients with primary lung metastases or late relapses. In this article, the results of the present Meta European Intergroup Cooperative Ewing Sarcoma Study (MetaEICESS) (tandem melphalan/etoposide [TandemME]) were compared with the result of the previous study (hyper melphalan/etoposide [HyperME]), both at 5 years, in a patient population within the same high-risk stratum to determine toxicity. PATIENTS AND METHODS: Among 54 eligible patients, 26 were treated according to the HyperME protocol, and 28 were treated according to TandemME protocol. Patients received six cycles of the Cooperative Ewing Sarcoma Study treatment in HyperME and six cycles of the EICESS treatment in TandemME as induction chemotherapy. Patients also received involved-compartment irradiation for local intensification and myeloablative systemic intensification consolidation with hyperfractionated total-body irradiation (TBI) combined with melphalan/etoposide in HyperME or two times the melphalan/etoposide in TandemME followed by autologous stem-cell transplantation. RESULTS: The event-free survival (EFS) rate +/- SD in HyperME and TandemME was 22% +/- 8% and 29% +/- 9%, respectively. The dead of complication rate was 23% in HyperME and 4% in TandemME. CONCLUSION: TandemME offers a decent, albeit still not satisfactory, rate of long-term remissions in most advanced ETs (AETs), with short-term treatment and acceptable toxicity. TBI was not required to maintain EFS level in this setting but was associated with a high rate of toxic death. Future prospective studies in unselected patients are warranted to evaluate high-dose therapy in an unselected group of patients with AET.

Adolescent↗
PubMed2002

Population-based genetic alterations in Ewing's tumors from Japanese and European Caucasian patients.

BACKGROUND: The incidence of Ewing's tumors (ETs) is lower in Asians or African-Americans than in Caucasians. PATIENTS AND METHODS: Japanese ETs were available for analysis of chromosomal aberrations by comparative genomic hybridization (n = 16) and for expression of chimeric EWS transcripts by reverse-transcriptase polymerase chain reaction (n = 11). These results in Japanese patients were compared with those of 62 ETs in European Caucasian patients registered in the European Intergroup Cooperative Ewing's Sarcoma Study. RESULTS: Japanese patients with ET had lower overall survival (P = 0.0446) and relapse-free survival (P = 0.0371) compared with European Caucasian patients. Ten of 11 Japanese ETs and 31 of 62 European Caucasian ETs had type I (EWS exon 7 to FLI1 exon 6) fusion transcripts. In Japanese ETs, the median numbers of chromosomal aberrations were 2.0 and 6.0 in 11 primary tumors and five relapsed tumors, respectively. In European Caucasian ETs, the median number of changes were 2.5 and 5.0 in 52 primary and 10 relapsed tumors, respectively. Frequent gains were 8q (38%), 8p (31%) and 12q (25%) in Japanese ETs and 8q (52%), 8p (48%) and 12q (19%) in European Caucasian ETs. Frequent losses were 19q (44%), 19p (38%) and 17p (25%) in Japanese ETs and 16q (21%), 19q (18%) and 17p (15%) in European Caucasian ETs. The incidence of losses of 19p (P = 0.0215) and 19q (P = 0.0277) were significantly higher in Japanese ETs than in European Caucasian ETs. An amplification (1p33-p34) was observed in only one Japanese ET. CONCLUSIONS: Japanese patients with ET in this study had a worse prognosis than European Caucasian patients. In molecular genetic analyses, Japanese ETs had a higher frequency of loss of chromosome 19 than European Caucasian ETs. Different genetic aberrations may explain the different incidences and prognoses of ET between Caucasian and Japanese patients.

Adolescent↗
PubMed2002

Targeting CD19 with genetically modified EBV-specific human T lymphocytes.

Human Epstein-Barr virus-specific T cells were genetically modified to express chimeric receptors specific for human CD19, which is expressed on the cell surface of most B cell malignancies. The receptor-modified EBV-specific T cells can be expanded and maintained long term in the presence of EBV-infected B cells. They recognize autologous EBV-infected targets through their conventional T cell receptor, and allogeneic EBV-infected targets and tumor targets through their chimeric receptor. They efficiently lyse both EBV and CD19-positive tumor targets in the absence of background cytotoxicity against CD19-negative targets. Donor-derived EBV-specific T cells expressing chimeric anti-tumor receptors may represent a source of effector cells that could be safely administered to leukemia patients to eradicate minimal residual disease after allogeneic bone marrow transplantation.

Antigens, CD19↗
PubMed2001

Genetic imbalances revealed by comparative genomic hybridization in Ewing tumors.

Ewing tumors are characterized by reciprocal translocations involving the EWS gene on 22q12 fused to ETS transcription-factor family members. Little is known about further aberrations contributing to tumor development and progression. Sixty-two frozen tumors with known EWS rearrangements (52 primary tumors, 10 relapses) of ET patients registered in the EICESS protocol were analyzed by comparative genomic hybridization (CGH). The median number of changes in 52 primary and 10 relapsed cases was 2.5 and 5.0 per tumor (P = 0.153). Frequent abnormalities included gains of chromosomes 8, 12, 20, and 1q and losses of 16q and 19q. Neither number nor type of aberration was associated with histology, tumor size, disease stage, tumor localization, or histologic tumor response to chemotherapy. Among the 52 primary tumors, 26 with Type I fusion (EWS exon 7 to FLI1 exon 6) and 26 with other fusion types had a median of 2.0 and 3.0 aberrations per tumor, respectively (P = 0.031). Combinations of gains of chromosomes 8 and 12, gains of chromosome 20, and either gains of 8q or 18q and losses of 16q and 17p frequently occurred. The cumulative overall survival (OAS) was different between 35 patients with <5 aberrations and 13 patients with > or =5 aberrations (P = 0.009). Univariate analysis showed that patients with gains of 1q, 2q, 12, and 20 or losses of 16q and 17p had significantly lower OAS than those without aberrations. By multivariate analysis, loss of 16q (relative risk [RR] = 5.3; P = 0.0006) was an independent prognostic factor.

Adolescent↗
PubMed2000

Telomerase is a strong indicator for assessing the proneness to progression in neuroblastomas.

BACKGROUND: As traditional parameters do not ensure completely accurate prognostic grouping in neuroblastoma (NB), new molecular markers are needed for assessing the individual patient's prognosis more precisely. PROCEDURE, RESULTS, AND CONCLUSIONS: Based on 133 NB, we show that telomerase activity (TA) is a powerful, independent prognostic marker for all stages and is capable of differentiating between good and poor outcome in putative 'favorable' clinical or biological subgroups of NB patients. Analysis of gene and protein expression of telomerase subunits suggests that the presence or absence of TA in NB is strongly correlated with expression levels of both the catalytic subunit hTERT and the internal RNA component (hTR).

Disease Progression↗
PubMed2000

Telomerase activity and telomerase subunits gene expression patterns in neuroblastoma: a molecular and immunohistochemical study establishing prognostic tools for fresh-frozen and paraffin-embedded tissues.

PURPOSE: We have recently demonstrated that telomerase activity (TA) is an independent prognostic factor in neuroblastomas. In the present study, the prognostic impact of TA and gene expression of the three major telomerase subunits is evaluated by molecular and immunohistochemical techniques in fresh-frozen and paraffin-embedded tissues. PATIENTS AND METHODS: One hundred thirty-three neuroblastomas of all stages were analyzed for TA. The TA levels of 75 neuroblastoma cases were correlated with gene expression of telomerase subunits hTRT, human telomerase RNA (hTR), and telomerase protein 1 (TP1) by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), using an innovative approach on the LightCycler instrument (Roche Diagnostics, Mannheim, Germany). For selected cases, the applicability of RT-PCR and immunohistochemistry for hTRT expression analysis was investigated in paraffin-embedded tissues. TA and subunit expression patterns were correlated with traditional prognostic indicators and disease outcome. RESULTS: TA was present in a total of 39 (29.3%) of 133 neuroblastomas and in 31 (29.8%) of 104 initial neuroblastomas without cytotoxic pretreatment. TA was significantly correlated with both event-free and overall survival (P <.0001). Furthermore, we found a significant correlation between expression levels of TA and hTRT (P <.0001) as well as hTR (P <.001). Multivariate analysis revealed only TA and tumor stage but not serum lactate dehydrogenase, MYCN amplification, or age at diagnosis as independent prognostic factors. CONCLUSION: The significant correlation with clinical outcome strongly recommends that analysis of TA be incorporated into the clinical investigation of each individual neuroblastoma at the time of diagnosis. Because the mere presence or absence of TA without further quantification is sufficient basis for predicting disease outcome, the telomeric repeat amplification protocol assay could be complemented with but not replaced by analysis of hTRT or hTR expression.

Biomarkers, Tumor↗
PubMed1999

Limb salvage and outcome of osteosarcoma. The University of Muenster experience.

One hundred thirty-six patients with non-metastatic high grade osteosarcoma treated from 1978 to 1994 in one institution with a multidisciplinary approach that included intravenous neoadjuvant chemotherapy were studied to evaluate which factors influence the outcome of modern orthopaedic therapy. Anatomic location, tumor volume, surgical margins, complications, and functional outcome were analyzed. Seventy-nine patients had a limb salvage procedure, 21 had a rotationplasty, and 33 had an amputation. Limb salvage consisted of 32 endoprostheses, 39 allograft replacements, six autograft replacements, and two shortening procedures. Three patients died during preoperative chemotherapy treatment. At a mean followup of 43 months, 81 patients continue to be disease free, three are alive after local recurrence, 17 are alive after having metastatic lesions, five are alive with metastatic lesions present, and 30 patients died of their disease. Forty-seven patients had pulmonary metastatic lesions, 14 had osseous metastatic lesions, three had abdominal metastatic lesions, two had lymphatic metastatic lesions, and eight patients had skip metastatic lesions. Prognosis correlated with chemotherapy response, surgical margins, and tumor volume. The minor complication rate for limb salvage was 4% and the major complication rate was 52%. Amputations had a 6% minor complication rate and 34% major complication rate. Rotationplasties had 10% minor and 48% major complication rates. The Musculoskeletal Tumor Society functional evaluation after limb salvage showed that 23 (38%) patients had more than 75% of the maximum functional score, 34 (56%) were from 50% to 75%, and three (5%) less than 50%. Of the rotationplasties, six (67%) were functionally better than 75% and three (33%) were functionally better than from 50% to 75%. In the group of amputations, 13 (56%) were from 50% to 75%, and 10 (44%) less than 50%. The extent of preoperative necrosis, surgical margins, and tumor volume are the most important prognostic factors. The increase in limb salvage procedures and the better long term survival of patients results in a higher rate of immediate and delayed complications. Functional outcome after rotationplasty is superior to limb salvage reconstruction and amputation.

Bone Neoplasms↗
PubMed1999

EWS-FLI1 and EWS-ERG gene fusions are associated with similar clinical phenotypes in Ewing's sarcoma.

PURPOSE: There are a variety of solid tumors in which alternative chromosomal translocations generate related fusion products. In alveolar rhabdomyosarcoma and synovial sarcoma, these variant fusions have been found to have major clinical significance. We investigated whether the two alternative gene fusion products, EWS-FLI1 and EWS-ERG, define different clinical subsets within the Ewing's sarcoma family of tumors. PATIENTS AND METHODS: We selected 30 cases of Ewing's sarcoma with the EWS-ERG gene fusion and 106 cases with the EWS-FLI1 fusion. Clinical data were obtained for each case and compared with the molecular diagnostic findings. RESULTS: There were no significant clinical differences observed between the two groups in age of diagnosis, sex, metastasis at diagnosis, primary site, event-free survival, or overall survival. CONCLUSION: Differences in the C-terminal partner in the Ewing's sarcoma family gene fusions are not associated with significant phenotypic differences.

Adolescent↗
PubMed1997

Efficacy and kinetics of bone marrow processing and enrichment of haematopoietic progenitor cells (HPC) by a large-volume apheresis procedure.

We investigated the efficacy of bone marrow (BM) processing by an automated large-volume apheresis procedure (6 x original BM volume) in 10 paediatric and adult patients undergoing BM harvesting before myeloablative therapy. Volume-dependent kinetics during apheresis were analyzed by sequential collection of processed cells into a six-fold collection bag system with consecutive analysis of the single bags. BM processing resulted in an 83.3% (+/- 21) recovery of mononuclear cells (MNC), a 97.9% (+/- 1.1) reduction of erythrocytes (RBC) and a 87.7% (+/- 2.9) volume reduction. To determine volume-dependent kinetics of haematopoietic progenitor cell (HPC) enrichment during apheresis, leukocytes (WBC), mononuclear cells (MNC), CD34 cells and colony-forming cells (CFU-GM) were serially quantitated in subsequent collection bags. Large-volume BM processing significantly enhanced absolute yields of CD34+ cells (mean: 4.01 (+/- 2.81) x 10(6)/kg bw) and CFU-GM (mean: 1.92 (+/- 1.47) x 10(4)/kg bw) compared with the standard procedure (3 x BM volume) by 26.9% (+/- 10.9) and 27.2% (+/- 11.6), respectively. We concluded that large-volume apheresis for BM processing is an efficient technique significantly improving the yields of haematopoietic progenitor cells (HPC) without any relevant changes in the purity of the final product. Moreover, sequential collection and analysis of HPC represents a good model to investigate the volume-dependent kinetics and efficacy of BM processing.

Adolescent↗
PubMed1996

Randomized comparison of rotational chemotherapy in high-risk acute lymphoblastic leukaemia of childhood--follow up after 9 years. Coall Study Group.

UNLABELLED: A frequent change of drug combinations may circumvent drug resistance in the treatment of patients with acute lymphoblastic leukaemia (ALL). In study COALL 85/89 201 children with high-risk ALL were randomized to receive over a period of 8 months rotational chemotherapy with six drug combinations given either in slow rotation (SR) (each combination given twice in succession) or in rapid rotation (RR) (each combination given once with a repetition of the drug combinations). Treatment of central nervous system leukaemia consisted of cranial irradiation and intrathecal methotrexate. Both SR and RR treatment groups were then given continuation chemotherapy of oral 6-mercaptopurine and methotrexate until 2 years after the date of diagnosis. The 9-year event-free survival (EFS) rate for the whole group is 69% +/- 3%, and the survival rate 75% +/- 3% at a median follow up of 5.8 years. Failure to achieve remission at day 28 was the most important prognostic factor (EFS 12% +/- 7% vs. 75% +/- 3% in the remission group). In the RR group, 11/100 patients were not in remission at day 28 opposed to 7/101 patients in the SR group. Children aged < 1 year (6/6 relapses) or aged > or = 10 years had a worse prognosis (EFS 64% +/- 5% vs. 77% +/- 4% in patients 1-10 years old). After 5 years EFS was inferior in the RR group attributable to a significantly higher relapse rate in children with a WBC > or = 100/nl. The EFS at 9 years for all patients, however, is similar in both groups (SR 72% +/- 5% vs. RR 67 +/- 5%). CONCLUSION: The COALL 85/89 treatment protocol with early intensive therapy and rotation of different drug combinations offers longterm disease-free survival for children with high-risk ALL. a continuous 4-week exposure to one drug combination may be necessary to achieve optimal results, especially in children with a high leukaemic cell burden.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Chemical and immunological characteristics of four different L-asparaginase preparations.

We studied the differences in protein composition and immunologic reactivity of two E. coli-derived L-asparaginase (l-Asp) preparations (I and II), Erwinia-Asp (III) and PEG-modified E. coli l-Asp (IV). On gel filtration, each of preparations I-III showed three major peaks at 100, 270 and 460 KD, all with enzyme activity, whereas PEG-Asp showed peaks at 35 and 220 KD. On SDS-PAGE one major subunit could be identified at 32 KD (I and II) or 40 KD (III), whereas PEG-modified l-Asp could only be detected by lowering the polyacrylamide concentration and gave a single band above 200 KD. Using a polyclonal rabbit antibody generated against preparation I, only the E. coli l-Asp preparations (I and II) formed precipitin lines on Ouchterlony double diffusion. After freezing and thawing, preparation IV also reacted with this antibody. In sera from patients treated with preparation I, antibodies (detected by ELISA) reacted with preparations I and II but not with preparations III and IV. These results indicate that Erwinia-Asp (III) and PEG-Asp (IV) are distinct from E. coli preparations (I and II) by molecular weight and immunological behavior. They also provide an experimental rationale for the use of Erwinia-Asp as well as PEG-Asp in E. coli Asp-sensitized patients.

Asparaginase↗
PubMed1989

Elimination of l-asparaginase in children treated for acute lymphoblastic leukemia.

The elimination of l-asparaginase (l-Asp) was studied in 8 children treated for acute lymphoblastic leukemia according to the CoALL 82 protocol. The patients received four doses of l-Asp as a single agent during induction chemotherapy. We studied the elimination of l-Asp during the first infusion in 1 child, during the second in 3, during the third in 2 and during the forth in 2 children. Using Western blot technique and an experimental rabbit antibody to l-Asp, we were able to detect a single band at 32 kilodaltons (KD) in the serum of all patients between 4 and 36 h after infusion. The molecular weight remained unchanged and no other bands occurred during the time of observation. The detection limit of this method was calculated to 5 micrograms/ml using radial immunodiffusion. Incubation of l-Asp with pooled normal human serum caused no degradation of the enzyme during 48 h at 37 degrees C. Neither the total enzyme nor fragments were detectable in the urine of the patients collected during 8 h after l-Asp infusion. From these results we conclude that l-Asp is not cleaved by proteases in humans. The enzyme is most probably eliminated by the reticuloendothelial system.

Adolescent↗