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M Bamberg

Publications and source records attributed to M Bamberg.

At least 73 records · Page 4Linked to original sources
PubMed2000

Spectroscopic determination of skin viability. A predictor of postmortem interval.

We have demonstrated that skin viability decreases at a measurable rate following death in an animal model. The decreased skin viability was measured by fluorescein diacetate and ethidium bromide using fluorescence emission spectroscopy. There is significant decrease of the fluorescence intensity of the fluorescein diacetate assay between the 1-4 h, the 6-24 h, and the >40 h time points postmortem. For times between 6-24 h and >40 h postmortem the ethidium bromide assay showed consistent and significant increases in signal. The fluorescence measurements in this study showed that under the experimental conditions the time of death could be determined for <4, 6-24, and >40 hapotmotrem. The application of these assays in the field will require further study of the environmental factors.

Animals↗
PubMed1999

In vivo fluence rate and fractionation effects on tumor response and photobleaching: photodynamic therapy with two photosensitizers in an orthotopic rat tumor model.

The effect of fluence rate and light fractionation on phototoxicity was investigated in vivo in an orthotopic rat bladder tumor model. Two photosensitizers, benzoporphyrin derivative monoacid ring A and 5-aminolevulinic acid-induced protoporphyrin IX, were studied. For a given cumulative light dose of 30 J/cm2, enhanced tumor destruction was observed from both photosensitizers when using either lower fluence rates or fractionated light delivery. Photobleaching experiments in vivo demonstrated that the photobleaching rate, however, was not fluence rate dependent. The fluence rate and light fractionation effects on tumor phototoxicity lead to rapid local depletion in oxygen concentration that inhibited subsequent photochemical reactions necessary for efficient photodestruction of tumor cells. Nicotinamide did not enhance photodynamic therapy efficacy, suggesting that the added increase of oxygen within the tumor was not sufficient to enhance photodestruction of hypoxic cell fractions. The independence of the photobleaching rate with fluence rate suggests distinct mechanisms, at least in part, of photodestruction of the tumor and the photosensitizer and that the rate of photosensitizer photo-bleaching may not always be an appropriate monitor for singlet oxygen availability and photodynamic therapy dosimetry.

Aminolevulinic Acid↗
PubMed1999

Radiotherapy for stages I and IIA/B testicular seminoma.

Radiotherapy is generally accepted as a standard treatment for early-stage testicular seminoma. Relapse rates of 2% to 5% in clinical stage I and 10% to 20% in stage IIA/B (according to the Royal Marsden classification) can be achieved. Disease-specific survival reaches 100%. With such excellent cure rates, treatment-related side effects gain particular importance. Therefore, a prospective multicenter trial was initiated for radiotherapy of testicular seminoma with limited treatment portals and low total doses of irradiation. In clinical stage I, 483 patients were treated with 26 Gy to the para-aortic region only. In stage IIA, 42 patients and, in stage IIB, 18 patients received irradiation to the para-aortic and high iliac lymph nodes with 30 and 36 Gy, respectively. With a median time to follow-up of 55 months for stage I and 55.5 months for stage IIA/B, there were 18 (3.7%) and 4 (6.7%) cases of relapse in both treatment groups. Disease-specific survival was 99.6% in stage I and 100% in stage IIA/B. Acute toxicity was dominated by moderate gastro-intestinal side effects. No major late toxicity has been observed to date. Limited volume pure para-aortic treatment for stage I and para-aortic/high iliac irradiation for stage IIA/B with 26, 30 and 36 Gy, respectively, yields excellent cure rates with only moderate acute toxicity and is therefore recommended as standard treatment.

Adolescent↗
PubMed1999

Stimulation of CD95 (Fas) blocks T lymphocyte calcium channels through sphingomyelinase and sphingolipids.

Calcium influx through store-operated calcium release-activated calcium channels (CRAC) is required for T cell activation, cytokine synthesis, and proliferation. The CD95 (Apo-1/Fas) receptor plays a role in self-tolerance and tumor immune escape, and it mediates apoptosis in activated T cells. In this paper we show that CD95-stimulation blocks CRAC and Ca(2+) influx in lymphocytes through the activation of acidic sphingomyelinase (ASM) and ceramide release. The block of Ca(2+) entry is lacking in CD95-defective lpr lymphocytes as well as in ASM-defective cells and can be restored by retransfection of ASM. C2 ceramide, C6 ceramide, and sphingosine block CRAC reversibly, whereas the inactive dihydroceramide has no effect. CD95-stimulation or the addition of ceramide prevents store-operated Ca(2+) influx, activation of the transcriptional regulator NFAT, and IL-2 synthesis. The block of CRAC by sphingomyelinase metabolites adds a function to the repertoire of the CD95 receptor inhibiting T cell activation signals.

Animals↗
PubMed1999

Radiation sensitivity of human squamous cell carcinoma cells in vitro is modulated by all-trans and 13-cis-retinoic acid in combination with interferon-alpha.

PURPOSE: Retinoids and interferon-alpha (IFN-alpha) have been shown to exert antiproliferative and radiosensitizing effects. The present study was designed to determine differential effects of retinoids in combination with IFN-alpha on radiation toxicity of 5 human squamous cell carcinoma (SCC) cell lines. METHODS AND MATERIALS: Using clonogenic assays, the effects of all-trans (ATRA), 13-cis-retinoic acid (13cRA), and IFN-alpha on radiation toxicity were analyzed. Basal mRNA expression of the cytoplasmic retinoic acid binding protein, CRABP I, was determined in retinoid-sensitive and -insensitive cell lines by reverse transcriptase/polymerase chain reaction (RT-PCR). RESULTS: Treatment with ATRA, 13cRA, or IFN-alpha resulted in a cell line-specific inhibition of clonogenic survival. A comparison of retinoid-sensitive and insensitive cells revealed that retinoid sensitivity seems to be dependent on the basal expression level of CRABP I. ATRA, 13cRA, and IFN-alpha alone or in combination altered radiation sensitivity by affecting predominantly the alpha-component of the linear-quadratic dose-response curve. Likewise, depending upon the treatment condition the surviving fraction at 2 Gy (SF2) was decreased cell line-specifically. Combined treatment with ATRA or 13cRA and IFN-alpha markedly enhanced radiation cytotoxicity. CONCLUSION: These in vitro data indicate that the combined treatment with retinoids, IFN-alpha, and ionizing radiation could be beneficial for patients presenting with SCC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[Relevance of the radioprotective effect of sodium selenite].

MATERIAL AND METHOD: Based on the mode of action of Na2SeO3 as a radical scavenger in vitro culture experiments using normal human skin fibroblasts and squamous cell carcinoma cells were performed to investigate the potential role of Na2SeO3 as a radioprotector for normal cells. Therefore, comparative studies of combined treatment, i.e. radiation exposure +/- Na2SeO3 in single-dose (0 to 7 Gy) and multiple fractionated-dose (5 x 2 Gy), were applied to differentiate the radiation response of normal and tumor cells depending upon the treatment protocol. RESULTS: The results indicate that Na2SeO3 under both radiation exposure conditions positively modulates the radiation response of normal fibroblasts in a sense of the radioprotective effect. On the contrary, human tumor cells are not affected by the radioprotective capacity of Na2SeO3 neither under single-dose nor fractionated-dose irradiation. CONCLUSION: On the basis of the quantitative cell culture analyses, this study indicates for the first time the potential role of Na2SeO3 as a radioprotective compound for normal cells. It will be discussed to what degree differential expression of apoptotic cell death in normal and tumor cells contributes to the radiation response of normal and tumor cells.

Carcinoma, Squamous Cell↗
PubMed1999

The tyrosine kinase lck is required for CD95-independent caspase-8 activation and apoptosis in response to ionizing radiation.

Induction of apoptosis is a hallmark of cytostatic drug and radiation-induced cell death in human lymphocytes and lymphoma cells. However, the mechanisms leading to apoptosis are not well understood. We provide evidence that ionizing radiation induces a rapid activation of caspase-8 (FLICE) followed by apoptosis independently of CD95 ligand/receptor interaction. The radiation induced cleavage pattern of procaspase-8 into mature caspase-8 resembled that following CD95 crosslinking and resulted in cleavage of the proapoptotic substrate BID. Overexpression of dominant-negative caspase-8 interfered with radiation-induced apoptosis. Caspase-8 activation by ionizing radiation was not observed in cells genetically defective for the Src-like tyrosine kinase Lck. Cells lacking Lck also displayed a marked resistance towards apoptosis induction upon ionizing radiation. After retransfection of Lck, caspase-8 activation and the capability to undergo apoptosis in response to ionizing radiation was restored. We conclude that radiation activates caspase-8 via an Lck-controlled pathway independently of CD95 ligand expression. This is a novel signaling event required for radiation induced apoptosis in T lymphoma cells.

Antibodies↗
PubMed1999

[Quality assurance in radio-oncology/radiotherapy: basic considerations].

Since 1994 the German Radiooncological Society has established a special commission for quality assurance in radiation oncology. The working agenda covers guidelines for dosimetry, infrastructure and organisation of a radiooncological department. The efforts are in close cooperation with the quality assurance programs of the EORTC. Corresponding guidelines are being published. They can be applied to create a quality assurance system in a radiooncological department. They are not considered definitive and are still receptive to benefit from further modifications.

Germany↗
PubMed1999

Geometric accuracy of field alignment in fractionated stereotactic conformal radiotherapy of brain tumors.

PURPOSE: To assess the accuracy of field alignment in patients undergoing three-dimensional (3D) conformal radiotherapy of brain tumors, and to evaluate the impact on the definition of planning target volume and control procedures. METHODS AND MATERIALS: Geometric accuracy was analyzed in 20 patients undergoing fractionated stereotactic conformal radiotherapy for brain tumors. Rigid head fixation was achieved by using cast material. Transfer of stereotactic coordinates was performed by an external positioning device. The accuracy during treatment planning was quantitatively assessed by using repeated computed tomography (CT) examinations in treatment position (reproducibility of isocenter). Linear discrepancies were measured between treatment plan and CT examination. In addition, for each patient, a series of 20 verifications were taken in orthogonal projections. Linear discrepancies were measured between first and all subsequent verifications (accuracy during treatment delivery). RESULTS: For the total group of patients, the distribution of deviations during treatment setup showed mean values between -0.3-1.2 mm, with standard deviations (SD) of 1.3-2.0 mm. During treatment delivery, the distribution of deviations revealed mean values between 0.7-0.8 mm, with SDs of 0.5-0.6 mm, respectively. For all patients, deviations for the transition to the treatment machine were similar to deviations during subsequent treatment delivery, with 95% of all absolute deviations between less than 2.8 and 4.6 mm. CONCLUSION: Random fluctuations of field displacements during treatment planning and delivery prevail. Therefore, our quantitative data should be considered when prescribing the safety margins of the planning target volume. Repeated CT examination are useful to detect operator errors and large random or systematic deviations before start of treatment. Control procedures during treatment delivery appear to be of limited importance. In addition, our findings should help to determine "cut-off points" for corrective actions in stereotactic conformal radiotherapy of brain tumors.

Brain Neoplasms↗
PubMed1999

HIT '91 (prospective, co-operative study for the treatment of malignant brain tumors in childhood): accuracy and acute toxicity of the irradiation of the craniospinal axis. Results of the quality assurance program.

BACKGROUND: It was the aim of the quality control program of the randomized trial HIT '91 (intensive chemotherapy before irradiation versus maintenance chemotherapy after irradiation) to assess prospectively the quality of neuroaxis irradiation with respect to the protocol guidelines and to evaluate acute toxicity with respect to treatment arm. PATIENTS, MATERIALS AND METHODS: Data of 134 patients undergoing irradiation of the craniospinal axis were available. Positioning aids, shielding techniques, treatment machines, choice of energy, total dose and fractionation were evaluated. A total of 651 simulation and verification films were analyzed to assess the coverage of the clinical target volume (whole brain, posterior fossa, sacral nerve roots) and deviations of field alignment between simulation and verification of first treatment. Field matching between whole brain and adjacent cranial spinal fields was analyzed with respect to site and width of junction. Acute maximal side effects were evaluated according to a modified WHO score for neurotoxicity, infections, skin, mucosa and myelotoxicity. RESULTS: In 91.3% of patients contemporary positioning aids and individualized shielding techniques were used to assure a reproducible treatment. In 98 patients (73.1%) linear accelerators and in 36 patients (26.8%) Cobalt machines were used. Single and total dose were administered according to the protocol guidelines in more than 90% of patients. In 20.2% of patients the cribriform plate, in 1.4% the middle cranial fossa and in 21.1% the posterior fossa and in 4.5% the 2nd sacral segment were incompletely encompassed by the treatment portals. Ninety-five percent of deviations of field alignment were less than 13.0 mm (whole brain) and 12 mm (cranial spinal field) with a random error between 4.9 and 7.6 mm (whole brain) and 6.9 mm and 9.9 mm (spinal canal), respectively. In 77.5% of patients the junctions between whole brain and cranial spinal fields were placed without a gap. A gap between 5 and 10 mm was left in 15 patients (18.7%), exceeding 10 mm in 3 patients. Acute neurotoxicity and skin reactions were mild, the rate of infections was low in both treatment arms. However, myelotoxicity resulted in interruptions of radiotherapy in 31.9% after intensive chemotherapy as compared to 20.0% without preceding chemotherapy. CONCLUSIONS: In the HIT '91 trial a precise radiotherapy of craniospinal axis has been performed in the majority of patients. Our findings indicate that the high quality is possibly an important contributing factor for the therapeutic outcome. However, preceding intensive chemotherapy caused marked toxicity of subsequent irradiation leading to a high rate of interruptions. Our database is subject to a future analysis of recurrences.

Brain Neoplasms↗
PubMed1999

13-cis retinoic acid in combination with interferon-alpha enhances radiation sensitivity of human squamous cell carcinoma cells of the oral cavity.

BACKGROUND: Preclinical and clinical trials demonstrated the antiproliferative and chemopreventive potential of 13-cis retinoic acid in combination with interferon-alpha. The present study was designed to determine the radiosensitizing potential of both drugs after single and combined treatment of human squamous-cell carcinoma cells of the oral cavity in vitro. MATERIAL AND METHODS: The study was performed using the human squamous-cell carcinoma cell line SCC4, which was originally established from a tumor of the oral cavity. Based on clonogenic assays, the inhibition of clonogenic activity and radiosensitizing potential of 13-cis retinoic acid and interferon-alpha after single or combined treatment without and with subsequent irradiation was determined. RESULTS: 13-cis retinoic acid (10 microM) and interferon-alpha (50 IU/ml) showed significant inhibition of clonogenic activity after single treatment. A combined treatment protocol resulted at least in a highly significant additive inhibition of clonogenicity. Treatment with both drugs (5 microM 13-cis retinoic acid, 25 IU/ml IFN-alpha) prior and post irradiation of the cells resulted in a pronounced enhancement of radiation toxicity resulting in significantly decreased SF2- and alpha-values. Combined treatment with both drugs was significantly more effective than single drug treatment. CONCLUSIONS: The data presented indicate that pre- and post-irradiation treatment with 13-cis retinoic acid and interferon-alpha significantly enhance the radiosensitivity of human squamous-cell carcinoma cells, SCC4, in vitro. Therefore, they support the initiation of clinical trials to test the radio-oncological value of such a treatment regime for squamous-cell carcinomas.

Antineoplastic Agents↗
PubMed1999

[Emergency rescue in accidents with HDR afterloading units].

PROBLEM: HDR brachyradiotherapy has minimized the exposure to radiation of the personnel working in this field. Nonetheless there are periodically reported troubles with afterloading units concerning the retraction of sources that require immediate action for the limitation of possible damage. LEGAL PRINCIPLES ACCORDING TO THE GERMAN REGULATION CONCERNING PROTECTION AGAINST RADIATION (STRAHLENSCHUTZVERORDNUNG = STRLSCHV): If in afterloading brachyradiotherapy the radiation source remains extended through malfunction we deal with an emergency according to the StrlSchV. The rescue personnel should be chosen in accordance with section 50 StrlSchV (Table 1). ORGANIZATION OF THE RESCUE OF THE PATIENT: The quickest possible rescue of a patient in an emergency demands an unequivocal definition of responsibilities. Our recommendations in this instance: the physicist is responsible for the organization of the emergency rescue. The radiation oncologist in charge informs himself about the necessary emergency measures before starting the treatment and carries out the emergency rescue. If the physicist diagnoses a failure in the retraction of the source he tries to remove the failure. If he doesn't succeed in retracting the source the radiation oncologist carries out the rescue of the patient. The organizational structure of the clinic allowing, the emergency physician should invariably be the physician who placed the applicator. In the emergency rescue the radiation oncologist should be protected by a lead barrier (Figure 1, Table 2) and use manipulators (Figure 1). DOSE ASSESSMENT IN PERSONNEL AND PATIENT: The radiation exposure of the rescue personnel is calculated from the photon-equivalence dose HX with the help of the dose-rate constant of 192Ir (Table 3). According to the same procedure there can be evaluated the local radiation exposure of the patient concerned (Table 3). CONCLUSIONS: Generally speaking, all considerations regarding the topic of emergency rescue should always start out from a worst-case scenario. Of all the people involved the patient is the one who is most exposed if the radiation source is located inside his or her body. If an emergency rescue is necessary the radiation exposure of patient and personnel can only be minimized by a quick rescue. This end requires a properly equipped emergency workplace, good training of all the people concerned, and regular exercises of the rescue procedures. A well-practiced emergency management can be of life-saving importance for the patient.

Brachytherapy↗
PubMed1999

Chemotherapy in the treatment of recurrent glioblastoma multiforme: ifosfamide versus temozolomide.

PURPOSE: Despite the progress made in neurosurgery and radiotherapy, the prognosis of glioblastoma multiforme (GB) is poor, due to the lack of an effective salvage therapy. In vitro analysis revealed activity for ifosfamide and temozolomide. The usefulness of these agents in recurrent disease was investigated. METHODS: Six adult patients with recurrent GB received one to four courses of 1,500 mg/m2 ifosfamide given over 5 days intravenously. Furthermore, temozolomide (100-200 mg/m2) was given orally over 5 days to 14 patients. RESULTS: After ifosfamide treatment, one partial response and two cases of stable disease were observed. The median survival time was 24 weeks (range of 9-52 weeks). Toxicity analysis revealed one paranoid reaction, three grade III leukocytopenia, and one grade I-II nausea, anemia, and hematuria. Temozolomide therapy resulted in three partial responses and four cases of stable disease. The median survival time (Kaplan-Meier) was 21 weeks (range 4-64 weeks). The major toxicities were grade I-II nausea and hematological side effects (one case of grade IV leuko- and thrombocytopenia). CONCLUSIONS: Ifosfamide treatment might be a feasible approach, but it necessitates hospitalization. Temozolomide showed promising results. Due to its oral application, the patient's quality of life (time out of hospital) is favorable. Subgroups with improved survival were observed.

Adult↗
PubMed1999

Impact of localized radiotherapy on blood immune cells counts and function in humans.

Immune cells subsets were prospectively analyzed after localized radiotherapy (LRT). LRT reduced the levels of all lymphocyte subsets, with B-cells and naive T-cells being most sensitive. Lymphocyte function was suppressed, but still within the normal range. Rapid recovery of cytotoxic T-cells/natural killer cells after LRT and the functional suppression within normal levels explains the low incidence of infections after LRT.

Adolescent↗
PubMed1999

Evaluation of predictive factors for local tumour control after electron-beam-rotation irradiation of the chest wall in locally advanced breast cancer.

BACKGROUND AND PURPOSE: Different radiotherapy techniques are being used for chest wall irradiation after mastectomy. We review our results with the electron-beam-rotation technique in a series of 130 high risk breast cancer patients. The main end point of the study was local tumour control; secondary end points were disease free survival, and overall survival, as well as acute and late side effects. MATERIAL AND METHODS: From January 1990 to June 1995, 89 patients underwent electron-beam-rotation irradiation of the chest wall after primary mastectomy and axillary lymph node dissection (group I) and 41 patients after excision of local recurrent breast cancer (group II) with 4 x 2.5 Gy/week to 50 Gy total dose (4-12 MeV electrons depending on the thickness of the chest wall). In addition, irradiation of local-regional lymph nodes and/or a local boost of 10 Gy were applied dependent on the resection and node status. RESULTS: After a median follow up of 29 months (65% stadium III/IV) the 3 year local tumour control, disease free survival, and overall survival were 73%, 47%, and 75%, respectively. Local control in group I was 78% versus 60% in group II. Significant predictors for local tumour control, disease free survival, and overall survival were resection status (R0 versus R1/2) and estrogen receptor status (positive versus negative). In group I, tumour grading (GI-IIa versus GIIb-III) and estrogen receptor status were found to be additional significant prognostic factors for complete resected tumours. Five patients developed symptomatic pneumonitis (< 4%) and one patient developed a chronic fistula at the resection. A significant correlation between the degree of acute skin reaction and persistent pigmentation was observed. CONCLUSION: In high risk breast cancer patients postoperative irradiation with the electron-beam-rotation technique of the chest wall is an effective therapy resulting in 78% local tumour control at 3 years for locally advanced breast cancer and 60% for recurrent disease. The rate of acute and late toxicity is low. The degree of acute skin reaction correlates with the degree of persistent pigmentation.

Adult↗
PubMed1999

Therapeutic outcome and relation of acute and late side effects in the adjuvant radiotherapy of endometrial carcinoma stage I and II.

BACKGROUND AND PURPOSE: Adjuvant radiotherapy is the standard treatment for endometrial carcinoma. However, until now there has been no clear indication that radiotherapy in that setting improves survival. This calls for critical assessment of the relation between the expected benefit and the number and severity of postradiotherapeutic side effects. MATERIAL AND METHODS: In a retrospective study 159 consecutive patients with stage I and II endometrial carcinoma were treated with external radiotherapy and vaginal brachytherapy after hysterectomy and bilateral salpingoophorectomy (no surgical lymph node staging). Recurrence rates, survival and side effects were evaluated, in particular with regard to the relation of acute and late toxicity. RESULTS: Five percent of all patients developed a recurrence either in the abdomen or at distant locations. No pelvic relapses were diagnosed. Five-year relapse-free survival was 92% for stage IA + B, 84% for stage IC, and 79% for stage II disease. Acute toxicity was seen in 65.4% of patients, all grade 1 or 2, late toxicity grade 1 or 2 in 18.8%, grade 3 or 4 complications in 1.8%. The estimated 5-year freedom from late toxicity was 76.8%. Seventy-seven percent of all patients with treatment interruptions or premature end of therapy experienced late injury. In ten of 33 patients with late sequelae there was no free interval between early and late toxicity. No relation of radiation technique/fractionation and the rate of side effects was noticed. CONCLUSIONS: Adjuvant radiotherapy leads to excellent pelvic control, with few serious complications. Major acute toxicity shows significant correlation with the incidence of severe late injury, which we suggest to classify in part as consequential late effects.

Adult↗
PubMed1999

Ionizing radiation and the activation of caspase-8 in highly apoptosis-sensitive lymphoma cells.

PURPOSE: Ionizing radiation induces apoptosis in human lymphoma cells. However, the participating molecules and their exact order is unknown. Caspases are reported as essential cysteine proteases required for the activation and execution of programmed cell death. The activator caspase-8 is a key component of the CD95/Fas/APO-1 death receptor-triggered apoptosis pathway. Since contributing molecules for radiation-induced apoptosis and their exact order have not been analyzed in greater detail, the involvement of caspase-8 for radiation-induced apoptosis in human lymphoma cell lines was studied. MATERIALS AND METHODS: Apoptosis induction by CD95 stimulation and ionizing radiation was analyzed in eight different cell lines. In parallel, Western blotting tested activation of caspase-8. RESULTS: Activation of caspase-8 by ionizing radiation occurred in five cell lines and was associated with high apoptosis sensitivity. Caspase-8 activation and apoptosis was detectable in cells resistant to CD95 stimulation, so suggesting separate pathways for CD95 and radiation-induced caspase-8 activation. CONCLUSION: The activator caspase-8 is activated during radiation-induced cell death and, in some cases, ionizing radiation induces caspase-8 independently of the CD95 system.

Apoptosis↗