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Biomedical subjects

M Bamberg

Publications and source records attributed to M Bamberg.

At least 145 records · Page 8Linked to original sources

Radiation-induced alterations of the proliferation dynamics of human skin fibroblasts after repeated irradiation in the subtherapeutic dose range.

PURPOSE: The aim of this study was to determine the effect of single and multiple irradiations on the differentiation and proliferation pattern of the stem cell system of human fibroblasts. METHODS: The pattern of differentiation of fibroblast cultures was analyzed by morphological criteria using colony forming assays. Proliferation rates were assessed by cell counting and measuring the incorporation of BrdU. RESULTS: Ionizing radiation both in low and high dose ranges exerts differential effects on the cellular processes of differentiation and proliferation in human fibroblasts. Single irradiations of fibroblasts in the dose range of 1 to 8 Gy induced terminal differentiation into postmitotic fibrocytes at high percentage level. Irradiation of long-term cultures of fibroblasts with repeated doses of 0.2, 0.6 and 1.0 Gy revealed that only in cultures, which were irradiated repeatedly (x 10) with 0.6 and 1.0 Gy a marked reduction of the proliferation capacity was apparent. Inhibition of proliferation by repeated irradiations with cumulative doses up to 10 Gy was not more pronounced as compared to single irradiations. CONCLUSION: 1. These results of radiation-induced changes in the proliferation and differentiation pattern of cells may be a basis for the understanding of the cellular processes leading to radiation-induced fibrosis and tissue aging. 2. Multiple irradiations with single doses up to 1 Gy and cumulative doses up to 10 Gy did not change the radiosensitivity of fibroblast cultures regarding effects on cell proliferation.

Cell Differentiation↗

[Vitamin A in tumor therapy: significance of clinical and pre-clinical findings for radiologic oncology].

PURPOSE: Retinoids are a class of compounds structurally related to vitamin A which have been found to be active agents experimentally as well as clinically in the prevention and treatment of tumors. The data available suggest to study whether they might improve treatment results if combined with irradiation. METHODS: The clinical results in the prevention and treatment of cancer with retinoids are reviewed. In the context of experimental studies evaluating the antiproliferative effects of retinoids, cytokines and radiation alone or in combination our own experimental investigations analyzing a combination of all-trans-retinoic acid, interferon-alpha (IFN-alpha) and ionizing radiation in squamous cell carcinoma cell lines are described. RESULTS: There is a solid body of experimental and clinical data to combine retinoids with cytokines (e.g.IFN-alpha). Since it is known that vitamin A alters the radiation response in experimental tumors our analyses further support the combination of retinoids and IFN-alpha with ionizing radiation. CONCLUSIONS: We emphasize further clinical investigations evaluating the combined treatment with retinoids/IFN-alpha and ionizing radiation in squamous cell carcinomas such as head and neck tumors and cervical cancer.

Animals↗

Reproducibility of field alignment in difficult patient positioning.

PURPOSE: Quantitative assessment of the accuracy of field alignment in a homogeneous group of patients with difficult positioning (postoperative irradiation after total hip replacement). METHODS AND MATERIALS: In 95 patients linear and rotational discrepancies were measured between the simulation and first check film and between five consecutive verification films. RESULTS: For the total group of patients, all deviations were normally distributed with mean values of approximately zero and standard deviations of 4.0-8.0 mm (linear discrepancies) and 3.5-5 degrees (rotational discrepancies). Deviations were similar for the transition from simulator to the treatment machine and for subsequent treatment delivery, with 50% and 95% of absolute differences being less than 5 mm and 15 mm, respectively. CONCLUSIONS: Our analysis indicates that statistical fluctuations are considerably more important than errors introduced at start of treatment. Therefore, a first check film seems to be inadequate to predict the expected inaccuracies for the whole course of treatment. In addition, our results should help to prescribe appropriate safety margins for patients with difficult positioning.

Hip Joint↗

Malignant glioma: patterns of failure following individually tailored limited volume irradiation.

Treatment outcome was analyzed for 66 patients with malignant glioma treated with individually CT-planned multifield irradiation techniques. Total doses of 60 Gy were given, with the planning target volume (PTV) including 2 cm beyond the tumour indicated by preoperative CT examination. Median survival was 14 months, and 86% of recurrences occurred in the treated volume. Our results suggest that the used PTV and radiation technique should be appropriate in radiotherapy of malignant glioma.

Astrocytoma↗

Repeated CT examinations in limited volume irradiation of brain tumors: quantitative analysis of individualized (CT-based) treatment plans.

Deviations of the position of the isocenter were quantitatively assessed for CT-based limited volume irradiation of brain tumors. Of the linear deviations, 95% were within 10 mm and 3 mm during treatment planning and delivery, respectively. The application of face masks before CT planning improved the accuracy of field alignment. Repeated CT examinations seemed to be more important after simulation than during treatment delivery.

Brain Neoplasms↗

How relevant is secondary leukaemia for initial treatment selection in Hodgkin's disease?

Specific tools of decision analysis, a set of mathematical rules for simplifying complex decisions, were applied to evaluate the impact of secondary leukaemia on the selection of initial treatment in Hodgkin's disease (HD). For this purpose, a combined 'expected utility' considering survival, relapse free survival, and secondary leukaemia was determined for different treatment strategies. Our analysis revealed that considerations of secondary leukaemia for initial therapy should include the a priori estimation of all possible events which may occur after initial treatment, e.g. the probabilities of recurrence and success of salvage therapy. In early and intermediate stage HD, for example, the minimal risk of leukaemia after successful radiotherapy (RT) must be weighed against the increased risk after treatment failure and subsequent salvage therapy. Thus, the difference of expected risk of leukaemia between RT and combined modality treatment (CMT) is within 4% for HD, stage II B and near to 0% in stage III A. In advanced stage HD, the addition of RT to chemotherapy has no adverse effect on the expected utility of initial treatment. These conclusions are only marginally affected by reported differences in rates of recurrence, salvage success, and secondary leukaemia. Subjective quality of life considerations, such as the latency period between treatment and leukaemia and patients' attitudes towards the occurrence of leukaemia, did not significantly affect expected utilities. In summary, our results strongly suggest that presently there is no sound basis for reducing the intensity of initial treatment in HD to avoid secondary leukaemia.

Antineoplastic Agents↗

Photoimmunotherapy and biodistribution with an OC125-chlorin immunoconjugate in an in vivo murine ovarian cancer model.

Photodynamic therapy (PDT) is an experimental approach to the treatment of neoplasms in which photosensitisers (PSs) accumulated in malignant tissues are photoactivated with appropriate wavelengths of light. The target specificity of PSs may be improved by linking them with carrier macromolecules such as monoclonal antibodies (MAbs). OC125 is a murine MAb that recognises the antigen CA 125, which is expressed on 80% of non-mucinous ovarian tumours. A chlorin derivative conjugated to OC125 was shown to be selectively phototoxic to ovarian cancer and other CA 125-positive cells in vitro and ex vivo. We now report in vivo studies using an ascitic Balb/c nude mouse ovarian cancer model. Ascites was induced by intraperitoneal injection of cells from the human ovarian cancer cell line NIH:OVCAR3. Six weeks after injection, when the animals had developed ascites, biodistribution studies were carried out by injecting the immunoconjugate (IC) or free PS intraperitoneally and sacrificing the animals at 3, 6, 12, 24, 48, 72 and 168 h later. The PS was quantitated by extraction and fluorescence spectroscopy. For both the IC and free PS, peak tumour concentrations were reached at 24 h; however, the absolute concentrations for the IC were always higher (2- to 3-fold) than the free PS. Tumour to non-tumour ratios at 24 h for the IC were 6.8 for blood, 6.5 for liver, 7.2 for kidney, 5.7 for skin and 3.5 for intestine. Evaluation of viable tumour cells in ascites following in vivo PDT with a single light exposure demonstrated a dose-dependent relationship with fluence and IC concentration. However, there was significant treatment-related toxicity at all fluences. With multiple low-dose treatments, the percentage of viable tumour cells was also significantly reduced and there were no treatment-related deaths. These data suggest that, while photoimmunotherapy remains promising as a new treatment modality for ovarian cancers, careful quantitative dosimetry of both IC and light may need to be combined with multiple treatments (as with radiation therapy and chemotherapy) to control malignant disease yet maintain acceptable toxicity in vivo.

Animals↗

Intracranial germ cell tumors: a comprehensive update of the European data.

Intracranial germ cell tumors are rare tumor entities in childhood and adolescents. Extra- and intracranial germ cell tumors are identical in their histologic pattern and occur in preferential midline localizations such as the pineal and the suprasellar region. Germ cell neoplasms show increasing incidence rates over the last 30 years. The majority of intracranial germ cell neoplasms are germinomas. About 90% of the patients with pure germinomas can be salvaged by radiotherapy alone according to modern protocols. Non-germinomatous malignant CNS-germ cell tumors are considered to have a poor prognosis. In order to improve the survival of patients affected by these tumors different treatment approaches adding chemotherapy to conventional surgery and radiotherapy have been initiated by various study groups throughout the world. Due to the rarity of these neoplasms only a very limited number of patients has been enrolled in each study. In 1993 an international working group on these tumors was established by the International Society of Pediatric Oncology (SIOP).

Brain↗

[The clinical picture and therapy of malignant pleural mesothelioma].

BACKGROUND: In the general population malignant pleural mesothelioma is an uncommon tumor with an average annual incidence of 15 cases per million. Its biological behavior is characterized by an infiltrating and aggressive growth. Median survival ranges between 6 and 12 months. There are different therapeutic modalities (surgical treatment, radiotherapy, chemotherapy), which are used alone or in combination to influence the poor outcome of pleural mesothelioma. PATIENTS AND METHODS: We report about 7 of our own cases, treated with surgery and radiotherapy (4) or with a combination of surgery, radiotherapy and chemotherapy (3) and discuss the clinical aspects, diagnosis and the different ways of treatment of malignant pleural mesothelioma and its influence on survival. RESULTS AND CONCLUSION: The extrapleural pleuropneumonectomy should be reserved to patients with stage I disease. Radical operation here offers some prospect of long-term survival. Palliative surgery such as pleurectomy is the treatment of choice for extended disease. Radiotherapy using doses between 45 and 50 Gy is useful in a palliative setting. Anthracyclin or cisplatin based chemotherapy may be helpful in cases with disseminated disease. Prospective trials are necessary to further clarify the role of multimodality treatment programs for malignant pleural mesothelioma.

Aged↗

Spheroid control of malignant glioma cell lines after fractionated irradiation: relation to the surviving fractions at 2 Gy and colony forming efficiencies in a soft agar clonogenic assay.

Spheroid control doses (SCD50) were determined for ten human glioma lines after fractionated irradiation under oxic conditions. In addition, SF2 values and colony forming efficiencies (CFE) were measured in a soft agarose clonogenic assay. A significant relationship existed between the SCD50 values and the SF2-CFE data pairs (p = 0.01) but the SCD50 values were higher than expected from the SF2 and CFE values. This comparison shows the influence of environmental factors (different in both model systems) on reproductive tumour cell death after irradiation.

Cell Aggregation↗

Granulocyte colony-stimulating factor treatment of leucopenia during fractionated radiotherapy.

11 patients suffering from an isolated leucopenia during fractionated radiotherapy were treated with granulocyte colony stimulating factor (G-CSF). 4 of the patients received radiotherapy alone, and 7 patients received concomitant chemotherapy. G-CSF treatment was initiated at the occurrence of leucopenia and maintained for the duration of radiotherapy. The applied daily dose was 5 micrograms/kg subcutaneously. 10 of the 11 treated patients reacted with an increased leucocyte count, from an average of 1342 leucocytes per microliter (+/- 502/microliters) to 24,568 leucocytes per microliter (+/- 950/microliters). Neutrophil counts increased on average from 64.9% (+/- 13.9%) to 91.1% (+/- 2.3%) (n = 7). In 1 patient thrombocytopenia occurred during the continued radiotherapy. 1 other patient reacted with an unexplained fall of leucocytes after two doses of G-CSF and one fraction of mediastinal irradiation. Side-effects observed during G-CSF treatment consisted of mild bone pain (1/11) and transient increases of serum alkaline phosphatase levels (4/11). Our observations indicate that G-CSF treatment is well tolerated during continuous fractionated radiotherapy. Therefore, we conclude that G-CSF can be used clinically to alleviate neutropenia caused by radiotherapy or by combined radio-chemotherapy.

Adult↗

Simultaneous supra- and infradiaphragmatic irradiation in Hodgkin's disease.

From 1982 to 1989, 68 patients with Stages IA to IIIB Hodgkin's disease were treated by simultaneous supra- and infradiaphragmatic irradiation (SSI-RT). 46 patients received exclusive radiotherapy for Stages IA and IIA (extended mantle field irradiation (EMF) 31, and total lymphatic irradiation (TLI) 15). Combined modality treatment including pre-irradiation chemotherapy, was given to 22 patients (CH-EMF 12 and CH-TLI 10). The median follow-up was 64 months. 5-year overall survival was 94% in combined Stages IA and IIA, and 100% in Stage IIIA. 5-year freedom from relapse was 87% in combined Stages IA and IIA, and 80% in Stage IIIA. Toxicity was evaluated in 64 patients. Acute and long term toxicity was similar to previously reported data on sequential supra- and infradiaphragmatic irradiation. In SSI-RT prior chemotherapy affected pre-irradiation blood counts and was associated with delayed post-irradiation haematological recovery. The relative mean white blood cell (WBC) decrease ranged from 47% (EMF) to 61% (TLI). The mean platelet decrease ranged from 43% (EMF) to 80% (CH-TLI). Both prior chemotherapy and total lymphoid irradiation increased haematotoxicity. The mean duration of breaks ranged from 3.9 days in EMF to 14.9 days in CH-TLI. The mean treatment time, ranging from 43 days in EMF to 54 days in TLI, was significantly shorter than in sequential schedules (up to 112 days). Our results indicate that SSI-RT is an effective and safe treatment. Its use seems to be limited mainly by prior chemotherapy. As compared to sequential schedules, the risk of match line overlap is avoided, overall treatment time is decreased, and treatment costs are minimized.

Adolescent↗

Ultrasound diagnosis of splenic lymphoma: ROC analysis of multidimensional splenic indices.

To assess the efficacy of splenic size in the sonographic diagnosis of lymphomatous involvement of the spleen, the authors studied 31 patients with splenic lymphoma (Hodgkin's disease, 17 and non-Hodgkin's lymphoma, 14) and 218 individuals without evidence of splenic disease. All subjects were studied with both a linear and a sector transducer. The longitudinal, transverse and diagonal diameters of the spleen were measured, and two- and three-dimensional splenic indices were calculated. The analysis of the diagnostic performance of these criteria, compared by means of receiver-operating characteristic (ROC) curves, revealed that diagnosis of splenic involvement by malignant lymphoma was considerably more reliable with a sector than with a linear scanner. If the longitudinal diameter was measured with a sector scanner, sensitivities were 66% and 74%, at specificities of 95% and 90% respectively (cut-off points: 12.5 cm and 11.3 cm, respectively). For the sector scanner, there was no advantage in using other diameters or multidimensional indices. Additional ROC analysis of recently published data indicating excellent discrimination capacity of a computed tomography index revealed that these results were largely owing to patient selection. In contrast, our data suggest that the potential of current non-invasive assessment of splenic lymphoma is limited. However, ultrasound may eventually help to eliminate staging laparotomy in selected cases, e.g. in patients with low risk of abdominal disease and with increased surgical risk.

Adult↗

[Dosage specification at the ICRU reference point: the consequences for clinical practice. International Commission on Radiation Units and Measurements].

In the Department of Radiotherapy, University of Tübingen, dose specification is performed according to the new ICRU recommendations since June, 1991. The purpose was to prescribe, record and report photon beam therapy in a consistent way applicable to most clinical situations and to provide uniform criteria for a comparison of treatment results from different radiotherapy centers. For "level 2" plans (including CT planning), the concept of dose specification has been changed to the "ICRU reference point" instead of to form the isodose encompassing the target volume as we did previously. A total of 24 representative treatment plans have been analyzed to assess the consequences of this change on dose prescription, treatment technique, and the size of the irradiated volume. Our results revealed that the prescription of single and total doses have to be individually adjusted according to the specific treatment plans. ICRU recommendations on dose homogeneity may significantly affect treatment technique and field sizes. Small deviations in dose prescription may be of particular influence on late responding normal tissues ("double trouble" due to simultaneous adjustment of single and total doses). Detailed comparisons of individual treatment plans with respect to physical, biological, and clinical data are obviously necessary in order to make sure that the outcome of a radiation treatment is not deviating too much from the clinical experience based on the former dose specification concept.

Germany↗

[The clinical picture and therapy of aggressive fibromatosis (desmoids)].

Desmoid tumors are accounted among histologically benign soft tissue tumors. Though metastases do not occur the clinical course of the disease with their tendency to grow locally aggressive and to relapse after curative intended surgery is similar to sarcomas. After surgical excision adjuvant therapy of desmoid tumors is necessary in such cases, where a radical excision with a wide margin is not possible, or must be doubted or after the surgical excision of a locally recurrent tumor. Radiation doses of 50 to 60 Gy reduce the risk of local recurrence of desmoid tumors to 18%. In such cases, where surgery and radiotherapy have been leading to incomplete responses, systemic therapy with hormones (tamoxifen or progesterone), with alkylating agents (e. g. ifosfamide) or with prostaglandin antagonists (indomethacin) is possible. The published data on therapeutic responses to the treatment of desmoid tumors are scarce. We are reporting on seven of our own cases, treated with surgery and radiotherapy (four) or with a combination of surgery, radiotherapy, hormones and chemotherapy (three).

Adult↗