PubMed Health⌕ Search

Biomedical subjects

Dieter Körholz

Publications and source records attributed to Dieter Körholz.

11 recordsLinked to original sources
PubMed2006

Effect of drug-induced cytotoxicity on glucose uptake in Hodgkin's lymphoma cells.

BACKGROUND: In Hodgkin's lymphoma, F-18-fluoro-deoxy-d-glucose positron emission tomography (FDG-PET) is used for staging and response evaluation after chemotherapy. However, drug-mediated downregulation of glucose uptake in viable Hodgkin's lymphoma cells might limit the use of FDG-PET. METHODS: We analyzed the effect of etoposide on cell viability and uptake of F-18-fluoro-deoxy-D-glucose or the glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) in vitro. RESULTS: Etoposide induced a dose-dependent cytotoxicity in HDLM-2 cells which was significantly correlated with reduced FDG uptake. However, it also significantly increased the portion of viable cells which did not take up 2-NBDG. Interestingly, etoposide-induced cytotoxicity was mainly mediated via caspase-dependent mechanisms, whereas the cell death induced by deprivation of glucose was mediated via caspase-independent mechanisms. CONCLUSION: Etoposide-mediated reduction of glucose uptake by Hodgkin's lymphoma cells is mainly caused by cell death. In a small fraction of viable cells, etoposide might downregulate glucose transporters and/or hexokinase activity and by that inhibit glucose uptake. This, however, might not lead to false-negative results of response evaluation in Hodgkin's lymphoma patients after chemotherapy, because inhibition of glucose uptake itself seems to be a strong inducer of cell death. Altogether, this study provides important in vitro evidence to clarify the mechanisms by which FDG-PET monitors the effect of anti-cancer treatment in Hodgkin's lymphoma patients.

4-Chloro-7-nitrobenzofurazan↗
PubMed2006

Temporary diabetes mellitus secondary to a primary pancreatic Burkitt lymphoma.

Primary pancreatic lymphoma (PPL) is a rare form of extranodal lymphoma. So far, only in adults has a coincidence with diabetes mellitus (DM) been described. We report a nearly 9-year-old German boy presenting with a Burkitt lymphoma associated with a temporary insulin-dependent DM and exocrine insufficiency of the pancreas. After the patient went into remission, a spontaneous recovery of the endocrine pancreatic function was observed. On immunophenotyping, the lymphoma cells revealed expression of FasL suggesting a potentially apoptotic effect on pancreatic tissue. Beta cell impairment may have been caused by FasL resembling autoimmune diabetes.

Burkitt Lymphoma↗
PubMed2006

The role of IL-4 and IL-12 in the regulation of collagen synthesis by fibroblasts.

Chronic sclerodermifomic graft versus host disease is a rare but important complication of allogeneic hematopoietic stem cell transplantation that especially occurs in patients who are treated with donor lymphocyte infusions for relapse of a malignant disease. Today most knowledge about the pathogenesis of chronic Graft-versus-Host Disease is based on mice models. In this report we describe the development of an allogeneic in vitro model that allows studying the pathogenesis of chronic sclerodermifomic Graft-versus-Host Disease in the human setting. We report that priming of mononuclear cells in the presence of allogeneic fibroblasts and Interleukin (IL)-4 induces fibroblast collagen synthesis, whereas priming in the presence of IL-12 suppresses collagen synthesis during subsequent coculture of primed mononuclear cells with allogeneic fibroblasts. Since IL-12 is also known to mediate anti-tumor effects by stimulation of Natural Killer cell and Lymphokine Activated Killer cell activity, these findings indicate that treatment of patients with IL-12 or pretreatment of donor lymphocytes with IL-12 might strengthen a graft versus leukemia effect and at the same time decrease the risk of chronic sclerodermifomic Graft-versus-Host Disease development.

Animals↗
PubMed2005

Salvage therapy of progressive and recurrent Hodgkin's disease: results from a multicenter study of the pediatric DAL/GPOH-HD study group.

PURPOSE: To evaluate a salvage therapy (ST-HD-86) for patients with progressive and relapsed Hodgkin's disease after primary treatment in the pediatric DAL/GPOH studies. The essential chemotherapeutic regimens were ifosfamide, etoposide, and prednisone (IEP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). METHODS: One hundred seventy-six patients with progression (n = 51) or first relapse (n = 125) were enrolled by 67 centers. The median time from initial diagnosis to progression/relapse was 1.1 year (range, 0.1 to 15.3 years), and the patients' median age was 14.7 years (range, 4.3 to 24.5 years). Salvage chemotherapy consisted of two to three cycles of IEP alternating with one to two cycles of ABVD supplemented in part by one to two cycles of cyclophosphamide, vincristine, procarbazine, and prednisone or lomustine (CCNU), etoposide, and prednimustine. Radiotherapy was given to involved areas using individualized doses. In the 1990s, additional high-dose chemotherapy with autologous stem-cell transplantation (SCT) was introduced for patients with unfavorable prognosis. RESULTS: Disease-free survival (DFS) and overall survival (OS) after 10 years are 62% and 75%, respectively (SE, 4% each). Of 176 patients, 73 suffered second events. The risk-factor analysis revealed the time to progression/relapse as the strongest prognostic factor (P = .0001). Patients with progression have an inferior outcome (DFS, 41%; OS, 51%), whereas patients with late relapse (> 12 months after end of therapy) do well (DFS, 86%; OS, 90%), although none of them received SCT in second remission. CONCLUSION: The result can be considered favorable. Whereas the salvage strategy for progressive disease has to be optimized further, it is possible to reduce intensity and avoid SCT in late relapses after Hodgkin's disease in childhood/adolescence.

Adolescent↗
PubMed2004

Pulmonary tuberculosis in a child receiving intensive chemotherapy for acute myeloblastic leukemia.

The authors describe a 6-year-old boy who developed pulmonary tuberculosis during intensive chemotherapy for acute myeloblastic leukemia (AML). The diagnosis of tuberculosis was made by PCR from an open lung biopsy, while a bacterial culture was negative. The patient was treated with triple tuberculostatic drug therapy, followed by two-drug therapy, while receiving maintenance chemotherapy for AML, including thioguanine and cytarabine. Pulmonary infiltrates resolved within 2 months of treatment. However, possibly due to the bone marrow toxicity of the tuberculostatic drugs, the patient tolerated only low doses of cytostatic therapy. The boy is now 14 months off tuberculostatic treatment and 8 months off AML therapy. He is in remission of AML and tuberculosis.

Antineoplastic Agents↗
PubMed2003

Ethanol-lock technique in the treatment of bloodstream infections in pediatric oncology patients with broviac catheter.

PURPOSE: To assess the ethanol-lock technique as a means of treating central venous line infections. Bloodstream infections in patients with tunneled central venous catheters can lead to removal of the lines. METHODS: Twenty-eight children and adolescents aged 2 to 18 years, with different types of cancer, had Broviac catheters and presented with positive blood culture and clinical signs of infection between January 2000 and December 2001. The ethanol-lock technique was performed 24 times in 18 patients in addition to empiric (initially) and specific (after antibiogram) intravenous antibiotic treatment. In another 15 cases, 13 children were treated with systemic antibiotics alone. RESULTS: Sixty-seven percent of the patients treated with ethanol locks had no infectious relapse of any kind within 4 weeks of treatment or during subsequent aplasia, compared with 47% treated with systemic antibiotics alone. In one boy the catheter infection could not be cleared with systemic antibiotics alone, but after one course of ethanol locks no more blood culture-positive infectious episodes were observed. No severe clinical side effects of ethanol flush were observed. Mild symptoms that occurred were tiredness, headaches, dizziness, nausea, and light-headedness. CONCLUSIONS: The ethanol-lock technique appears to be a safe, well tolerated, and effective way to treat central venous line infections, even in small children. A prospective randomized study should be designed to compare antibiotic-lock, ethanol-lock technique, and systemic antibiotics alone in the treatment of device-associated bloodstream infection.

Adolescent↗
PubMedDate not supplied

Primary high-grade non-Hodgkin lymphoma of the trachea in an adolescent.

Lymphomas belong to the most treatable and curable malignant tumors of childhood. They should always be considered among differential diagnosis, even in unusual locations, and tumor material should be processed adequately to reach true diagnosis. The authors report on a 16-year-old adolescent with a tracheal lymphoma, a rare location of lymphoma in childhood. Because only formalin-fixed tumor material was obtained, pathology showed two differential diagnoses and the entity could never be fully clarified as anaplastic plasmacytoma or plasmoblastic lymphoma. Thus, full lymphoma diagnostic workup should be performed even in tumors with atypical location.

Adolescent↗
PubMedDate not supplied

Drug-induced caspase-3 activation in a Ewing tumor cell line and primary Ewing tumor cells.

Ewing sarcoma is a rare malignancy occurring in childhood and adolescence which has a prognosis of about 50% long-term event-free survival, depending on risk factors such as tumor volume, initial metastases at the time of diagnosis and tumor response to presurgical chemotherapy. In order to tailor therapy to the individual patient, new prognostic factors need to be identified. In this study, we showed that etoposide and actinomycin D kill Ewing tumor cells (RD-ES cell line) mainly via a caspase-dependent mechanism. Both drugs induced a significant caspase-3 activation, which can be detected with a new caspase-3 assay. Dose-response analyses showed that induction of cell death and caspase-3 activation is mediated by similar concentration ranges of both drugs. In addition to the cell line, caspase-3 activation was also shown during drug-mediated stimulation of freshly isolated cells from tumor biopsies. In conclusion, actinomycin D and etoposide stimulated caspase-3 activation in a Ewing tumor cell line and in freshly isolated tumor cells, causing drug-induced cell death. Thus, determination of caspase-3 activation might be a suitable method for drug sensitivity testing in patients with Ewing tumors before initiating treatment. This assay could therefore help individualize therapy in future tumor patients.

Adult↗