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Biomedical subjects

E Dühmke

Publications and source records attributed to E Dühmke.

At least 37 records · Page 2Linked to original sources
PubMed2001

Photofrin II as an efficient radiosensitizing agent in an experimental tumor.

BACKGROUND AND OBJECTIVE: The use of ionizing irradiation as radiation therapy (RT) for tumor treatment represents a well-established method. The use of photodynamic therapy (PDT), especially with Photofrin II, for tumor treatment is also known. Chemical modifiers enhancing the action of radiation therapy are well known and widely used in medicine. None of these compounds, however, is a selective radiosensitizer. MATERIALS AND METHODS: Several series of animal experiments were performed. The highly differentiated human bladder cancer cell line RT4 was implanted subcutaneously in nude mice. The mice were injected 10 mg/kg Photofrin II and irradiated with 5 Gy. RESULTS: Photofrin II has proved to be a chemical modifier of ionizing irradiation, enhancing the tumor doubling time (tumor growth) from 6.2 to 10.9 days in the control group with the use of irradiation and injection of porphyrin. CONCLUSION: Photofrin II shows a high activity as radiosensitizer and, in the future, can be used as a selective radiosensitizer for tumor treatment with ionizing radiation.

Animals↗
PubMed2000

Long-term impact of postoperative radiotherapy in carcinoma of the vulva FIGO I/II.

PURPOSE: Between 1953 and 1978, postoperative radiotherapy was used as an adjuvant therapy for carcinoma of the vulva that had not been treated with radical vulvectomy. We evaluated long-term results and possible prognostic factors. METHODS AND MATERIALS: Ninety-two patients were treated. Surgical procedures were simple vulvectomy, electrocoagulation, or local excision. Radiotherapy doses to the vulva ranged from 0 to 90 Gy. All patients received radiotherapy to the inguinal lymph nodes, ranging from 30 to 60 Gy. Thirty-year retrospective follow-up was done evaluating the records and statistical survival rates. RESULTS: Five-year actuarial survival rates in T1 patients were 71% (77% cause-specific survival rate), for T2 patients 43% (48% cause-specific survival rate). The difference between T1 and T2 patients was significant (p < 0.05). Patients with tumors of the labia minora had a significantly higher survival rate than those with different sites affected. Doses of 45 Gy or more to the vulva were sufficient to increase the 5-year cause-specific survival rate from 55% to 88%. The results in three subgroups were analyzed, group 1 having received electrocoagulation, but no radiotherapy of the vulva; group 2, local excision and doses of 40 Gy to the vulva; group 3, local excision and doses of 60 Gy to the vulva. There was a significant effect on 10-year cause-specific survival rates: 48% in group 1, 11% in group 2, and 88% in group 3. In multivariate analysis, the significant independent factors were T classification, tumor sites and-with only marginal significance-radiation doses to the vulva. CONCLUSIONS: The prognosis in early vulva carcinoma after nonradical surgery primarily depends on T classification and the site of the primary tumor. With univariate analyses, the dose has a significant effect on survival. In multivariate analyses the dose is a marginal independent factor in the whole group of patients. After nonradical surgery of early vulva carcinoma, the vulva should be irradiated resulting in better long-term survival.

Adult↗
PubMed2000

Magnetic resonance imaging (MRI) controlled outcome of side effects caused by ionizing radiation, treated with 780 nm-diode laser -- preliminary results.

BACKGROUND AND OBJECTIVE: Ionizing radiation therapy by way of various beams such as electron, photon and neutron is an established method in tumor treatment. The side effects caused by this treatment such as ulcer, painful mastitis and delay of wound healing are well known, too. Biomodulation by low level laser therapy (LLLT) has become popular as a therapeutic modality for the acceleration of wound healing and the treatment of inflammation. Evidence for this kind of application, however, is not fully understood yet. This study intends to demonstrate the response of biomodulative laser treatment on the side effects caused by ionizing radiation by means of magnetic resonance imaging (MRI). STUDY DESIGN/PATIENTS AND METHODS: Six female patients suffering from painful mastitis after breast ionizing irradiation and one man suffering from radiogenic ulcer were treated with lambda=780 nm diode laser irradiation at a fluence rate of 5 J/cm2. LLLT was performed for a period of 4-6 weeks (mean sessions: 25 per patient, range 19-35). The tissue response was determined by means of MRI after laser treatment in comparison to MRI prior to the beginning of the LLLT. RESULTS: All patients showed complete clinical remission. The time-dependent contrast enhancement curve obtained by the evaluation of MR images demonstrated a significant decrease of enhancement features typical for inflammation in the affected area. CONCLUSION: Biomodulation by LLLT seems to be a promising treatment modality for side effects induced by ionizing radiation.

Adult↗
PubMed2000

Effects of 780 nm diode laser irradiation on blood microcirculation: preliminary findings on time-dependent T1-weighted contrast-enhanced magnetic resonance imaging (MRI).

Laser therapy by low light doses shows promising results in the modulation of some cell functions. Various clinical studies indicate that laser therapy is a valuable method for pain treatment and the acceleration of wound healing. However, the mechanism behind it is still not completely understood. To explore the effect of a low-power diode laser (lambda = 780 nm) on normal skin tissue, time-dependent contrast enhancement has been determined by magnetic resonance imaging (MRI). In the examinations, six healthy volunteers (four male and two female) have been irradiated on their right planta pedis (sole of foot) with 5 J/cm2 at a fluence rate of 100 mW/cm2. T1-weighted magnetic resonance imaging is used to quantify the time-dependent local accumulation of Gadolinium-DPTA, its actual content in the local current blood volume as well as its distribution to the extracellular space. Images are obtained before and after the application of laser light. When laser light is applied the signal to noise ratio increases by more than 0.35 +/- 0.15 (range 0.23-0.63) after irradiation according to contrast-enhanced MRI. It can be observed that, after biomodulation with light of low energy and low power, wound healing improves and pain is reduced. This effect might be explained by an increased blood flow in this area. Therefore, the use of this kind of laser treatment might improve the outcome of other therapeutic modalities such as tumour ionizing radiation therapy and local chemotherapy.

Female↗
PubMed2000

Primary gastric B-cell lymphoma: results of a prospective multicenter study. The German-Austrian Gastrointestinal Lymphoma Study Group.

BACKGROUND & AIMS: Appropriate management of primary gastric lymphoma is controversial. This prospective, multicenter study aimed to evaluate the accuracy of endoscopic biopsy diagnosis and clinical staging procedures and assess a treatment strategy based on Helicobacter pylori status and tumor stage and grade. METHODS: Of 266 patients with primary gastric B-cell lymphoma, 236 with stages EI (n = 151) or EII (n = 85) were included in an intention-to-treat analysis. Patients with H. pylori-positive stage EI low-grade lymphoma underwent eradication therapy. Nonresponders and patients with stage EII low-grade lymphoma underwent gastric surgery. Depending on the residual tumor status and predefined risk factors, patients received either radiotherapy or no further treatment. Patients with high-grade lymphoma underwent surgery and chemotherapy at stages EI/EII, complemented by radiation in case of incomplete resection. RESULTS: Endoscopic-bioptic typing and grading and clinical staging were accurate to 73% and 70%, respectively, based on the histopathology of resected specimens. The overall 2-year survival rates for low-grade lymphoma did not differ in the risk-adjusted treatment groups, ranging from 89% to 96%. In high-grade lymphoma, patients with complete resection or microscopic tumor residuals had significantly better survival rates (88% for EI and 83% for EII) than those with macroscopic tumor residues (53%; P < 0.001). CONCLUSIONS: There is a considerable need for improvement in clinical diagnostic and staging procedures, especially with a view toward nonsurgical treatment. With the exception of eradication therapy in H. pylori-positive low-grade lymphoma of stage EI and the subgroup of locally advanced high-grade lymphoma, resection remains the treatment of choice. However, because there is an increasing trend toward stomach-conserving therapy, a randomized trial comparing cure of disease and quality of life with surgical and conservative treatment is needed.

Adult↗
PubMed1999

Long term results of definitive radiotherapy for cervical carcinoma using four applications of high dose rate afterloading.

BACKGROUND: In definitive radiotherapy for cervical carcinoma, combined modality treatment using external beam radiotherapy and brachytherapy is standard. Although the optimal number of afterloading applications is controversial, the majority of authors recommend three applications. METHODS: In this study, the authors investigated the use of 4 applications with iridium-192 afterloading with a dose of 7.5 grays (Gy). Standardized radiotherapy doses were adapted to the individual tumor anatomy using a prospective schedule. RESULTS: In the 73 study patients, actuarial and tumor-related 5-year survival rates by T classification were: T1b: 30% (100% cause specific survival); T2a: 55% (76% cause specific survival); T2b: 50% (60% cause specific survival); T3a: 50% (67% cause specific survival); T3b: 39% (50% cause specific survival); and T4a: 40% (40% cause specific survival). Morbidity, graded according to the National Cancer Institute's Common Toxicity Criteria (CTC) were low: CTC Grade 1: 7 patients (7.6%); CTC Grade 2: 7 patients (7.6%); CTC Grade 3: 1 patient (1.4%); and CTC Grade 4: 1 patient (1.4%). In a multivariate analysis, the T classification was the only significant independent prognostic factor for actuarial survival, tumor related (cause specific) survival, local tumor control and freedom of metastatic disease. The number of afterloading applications was an independent prognostic factor for local tumor control. CONCLUSIONS: Based on the long term results of the current study, external beam radiotherapy combined with 4 afterloading high dose rate applications (total of 30 Gy) appears to be clinically feasible and results in satisfactory survival rates and few side effects.

Adenocarcinoma↗
PubMed1999

Effects on the mitosis of normal and tumor cells induced by light treatment of different wavelengths.

OBJECTIVE: Although the background of laser therapy by means of low level energy and power is still only partially understood, there are nevertheless promising reports from clinical studies concerning pain treatment, the acceleration of wound healing, and the modulation of cell functions. In order to contribute to the understanding of such a phototherapeutic procedure cell experiments were performed. MATERIALS AND METHODS: The influence of light (lambda = 410, 488, 630, 635, 640, 805, and 1,064 nm and broad band white light) on the proliferation of cells was investigated on skeletal myotubes (C2), normal urothelial cells (HCV29), human squamous carcinoma cells of the gingival mucosa (ZMK1), urothelial carcinoma cells (J82), glioblastoma cells (U373MG), and mamma adenocarcinoma cells (MCF7) in a computer-controlled light treatment chamber. The cellular response was tested by way of the following methods: The rate of mitosis was determined by counting the single cells after Orcein-staining. The proliferation index measurements were based on the BrdU incorporation during the DNA synthesis. Statistics were performed using unpaired Student's t-test procedures, stating P < 0. 05 to be significant and P>0.05 not to be significant. RESULTS: Twenty-four hours after light treatment, a significant increase in the mitotic rate of J82 and HCV29 cells was determined when illuminated with lambda = 410 nm, lambda = 635 nm and lambda = 805 nm, respectively. C2 cells showed an increase only after lambda = 635 nm illumination. In all three cell lines, a maximum mitotic rate was determined after an irradiation between 4 and 8 J/cm(2), while a reduced mitotic rate was measured at 20 J/cm(2). MCF7, U373MG, and ZMK1 cells showed a slight decrease in the mitotic rate with increasing irradiation independent of the wavelength used. When an irradiation of 20 J/cm(2) was applied, all cell lines showed a slight decrease compared to the controls independent to the wavelength used. White light as well as lambda = 1,064 nm does not affect the mitotic rate in this irradiation range. No significant differences in the effects could be determined when the irradiance changed between 10 and 150 mW/cm(2) at certain irradiation values. The BrdU test did not show any significant alterations with respect to possible light induced processes compared to the controls. CONCLUSIONS: Dependent upon the irradiation parameter, light of a defined wavelength does affect the mitotic rate of both normal as well as tumor cells. It could be hypothesized that the action spectra of the cellular response indicate the participation of endogenous porphyrins and cytochromes as primary photoreceptors. Taking into account all light induced processes, the term biomodulation should preferably be used.

DNA↗
PubMed1999

Second malignancies after Hodgkin's disease: the Munich experience.

The occurrence of second malignancies (SM) is an important late event following the treatment of Hodgkin's disease (HD). We sought to determine the incidence, the risk factors, and the prognosis of SM in our population of patients with HD. A total of 1120 patients diagnosed with HD were registered at six participating institutions in Munich (calendar period 1974-1994). The mean follow-up for the development of SM was 9.1 years. A cumulative treatment score was calculated for both radio- and chemotherapy. The relative and absolute risks of SM were established. All SM were investigated for response to treatment and outcome. We observed 85 SM [eight leukemias, 22 non-Hodgkin's lymphomas (NHL), two plasma cell neoplasias, and 53 solid tumors]. Five patients developed third malignancies. The relative risk of developing a second neoplasm was compared with that within the normal population and was 3.1-fold. The risk varied according to the category of SM. Higher relative risks (20.5 and 25.9-fold), but lower absolute risks were observed for leukemias and non-Hodgkin's lymphomas. Solid tumors had lower relative risks (1.8-fold). Splenectomy increased the risk of SM (relative risk 4.4-fold versus 2.7-fold). The risk of SM did not correlate with the initial treatment (radio- or chemotherapy) and did not decrease with prolonged follow-up. The cumulative intensity of radiotherapy, chemotherapy, or the two modalities combined correlated with the risk of SM. Since some cases occurred early after diagnosis, not all second neoplasms can be considered treatment-associated. After 15 years, an actuarial risk of 11.7% was calculated for all SM, of 1.0% for leukemias, of 3.0% for NHL, and of 7.7% for solid tumors. The prognosis of SM varied between good (thyroid cancer, melanoma: median survival 5+ years), average (breast cancer, NHL), and poor (acute myeloid leukemias, lung cancers: median survival 9 months). With the exception of NHL, second cancers often occurred in topographic relation to the field of previous radiotherapy. Taken together, in our patient population, we observed all three categories of SM (solid tumors, leukemias, NHL). The risk for second leukemias is lower than in previous studies, whereas the risk of second NHL is somewhat higher. We confirm that splenectomy is a possible risk factor for SM. Even after correction for the age-specific cancer incidence, treatment intensity is associated with the development of second malignant tumors. Continued follow-up is mandatory after treatment for HD. Since the prognosis of most SM is unfavorable, early recognition and prevention are of the utmost importance.

Adolescent↗
PubMed1998

Influence of clodronate on breast cancer cells in vitro.

UNLABELLED: One of the major therapies of bone metastasis is administration of clodronate. But the influence of clodronate alone on tumour cells is not quite clear. Radiotherapy and administration of clodronate increasingly are used in combination. The influence of clodronate on radiosensitivity of tumour cells is not known. METHODS: We used MDA-MB-435S and MCF-7 cells (breast cancer) in vitro and exposed the cells to clodronate in different concentrations and different short application times. In a second experiment we added graded doses of radiotherapy to the cell cultures. All experiments were done under standard conditions of the colony test. RESULTS: At different concentrations and different incubation times clodronate is able to reduce the cell survival of MDA-MB-435S cells, but not of MCF-7 cells. Even very low concentrations of clodronate in the cell culture medium are sufficient to reduce the tumour cell survival of MDA-MB-435S down to 59%. This reduction is time and concentration dependent. Using irradiation, clodronate has definitively no influence on the radiosensitivity of MDA-MB-435S cells in vitro, but the shoulder of the survival curve of MCF-7 cells is markedly reduced, demonstrating reduced repair of sublethal radiation damage.

Aged↗
PubMed1998

[Indication and technic of radiation therapy in advanced high malignancy non-Hodgkin lymphoma].

The role of radiotherapy in the treatment of advanced high-grade NHL is not defined. Most experiences come from retrospective analyses or prospective randomized studies not evaluating primarily the indication of radiotherapy. Longtime results of the German-Austrian Multicenter Study are lacking. Possibilities of the radiotherapy consists of the radiotherapy of prior involved or bulky or slow responding regions in the adjuvant situation. In high risk groups, prophylactic brain irradiation may be useful. In recurrent patients, radiotherapy offers many possibilities of local palliation.

Female↗
PubMed1998

[Use of G-CSF (Neupogen) in multimodal treatment in radiotherapy].

BACKGROUND: Therapy-induced leukopenias with corresponding consequences repeatedly occur in radiotherapy using combined modalities treatment. In radiotherapy, where G-CSF (granulocyte-colony-stimulating-factor) is not licensed, G-CSF has been used successfully under individual circumstances. These results were confirmed in several studies with small patient groups. The aim of this study was to check former results in a larger patient group, to verify postulated side effects and specially to define a cost-effective schedule in the treatment with G-CSF (Neupogen). PATIENTS AND METHODS: In this surveillance trial 50, partially previously treated patients with different malignant tumors were treated with G-CSF. According to the probability of a leucocytosis lower than 1000/mm3, G-CSF (Neuropogen) was already given at leukocyte values lower than 2500/mm3 (500/mm3 bis 2450/mm3). It administered subcutaneously every other day, based on body weight until reaching normal leucocyte levels. RESULTS: In 92% of the patients the increase of leucocytes occurred in the first 24 hours. On average G-CSF was given 4.9 times per patient. Patients without prior therapies or less complex therapies needed less G-CSF applications (3.5 to 5.8 applications). Due to individually varying leucocyte courses the G-CSF therapy was started with leucocyte values between 500/mm3 and 2450/mm3. Patients who were treated with up to 3 G-CSF applications had higher leucocyte levels than those with 4 or more applications (1620/mm3 to 1250/mm3). Leucopenia related infections, therapy interruptions or break-offs did not occur. Besides light "flu like" symptoms in 14% of the patients, no side effects were observed. CONCLUSIONS: When a decrease of leucocyte values lower than 1000/mm3 is expected, the most cost-effective treatment is given when starting the interventional G-CSF administration already at leucocyte values around 1600/mm3. Leucopenias can be treated effectively, with little side effects and in a cost-effective way when G-CSF is given on time.

Adult↗
PubMed1998

BEACOPP: a new regimen for advanced Hodgkin's disease. German Hodgkin's Lymphoma Study Group.

The BEACOPP chemotherapy regimen for advanced Hodgkin's disease employs a rearranged schedule permitting a shortened three-week cycle. With haematological growth factor support, the dosages of cyclophosphamide, etoposide and adriamycin could be moderately escalated. The 3-armed multicentre HD9 trial (recruitment 1993-1998; 1300 patients randomised) aimed to compare BEACOPP with the standard COPP/ABVD chemotherapy and to detect and measure the gain in efficacy, if any, due to moderate dose escalation of BEACOPP. Eight cycles were given, followed by local irradiation. The most recent interim analysis, with 689 evaluable patients, circa 40% of all expected events and a median observation time of 27 months, showed significant differences in progression rate (P) and in two-year freedom from treatment failure (F) between the treatment arms, with escalated BEACOPP (P = 2%, F = 89%) better than baseline BEACOPP (P = 9%, F = 81%) better than COPP/ABVD (P = 13%, F = 72%). Survival was not significantly different. Acute toxicity was more severe due to dose escalation, but remained manageable. These preliminary results suggest that BEACOPP improves efficacy. Moderate dose escalation is feasible with G-CSF support and appears likely to make a worthwhile improvement in the cure rate. The results must await confirmation (or otherwise) by the final analysis including all randomised patients and sufficiently mature data.

Adolescent↗
PubMed1997

Biomodulative effects induced by 805 nm laser light irradiation of normal and tumor cells.

The influence of light emitted from a diode laser centred at lambda = 805 nm was investigated on murine skeletal myotubes (C2), normal urothelial cells (HCV29), human squamous carcinoma cells of the gingival mucosa (ZMK) and urothelial carcinoma cells (J82) in a computer-controlled irradiation chamber. Cells were treated with varying fluences between 0 and 20 J cm-2. The response was tested by analysis of the mitotic index using single cell counting after Orcein staining and proliferation index based on BrdU incorporation during DNA synthesis. While the mitotic index of C2, HCV29 and J82 cells increased at a fluence of 4 J cm-2, irradiation with fluences of 20 J cm-2 resulted in a slight decrease. ZMK tumor cells showed a decrease of the mitotic index with both fluences. No significant differences could be determined when using irradiances between 10 mW cm-2 and 150 mW cm-2. The BrdU test after irradiation showed no significant effects compared to the controls in each cell line.

Animals↗
PubMed1996

Randomized trial with early-stage Hodgkin's disease testing 30 Gy vs. 40 Gy extended field radiotherapy alone.

PURPOSE: To evaluate whether or not a total dose (TD) of 30 Gy is sufficient for treatment of assumed subclinical Hodgkin's Disease compared to 40 Gy TD with early stage Hodgkin's Disease (ESHD). METHODS AND MATERIALS: In a prospective multicenter trial, 376 patients with laparotomy-proven ESHD stages PS IA to PS IIB without risk factors such as large mediastinum, massive splenic involvement, extranodal disease, elevated erythrocyte sedimentation rate (ESR), and/or three or more involved lymph node areas were randomly allocated either to receive (ARM A) 40 Gy TD extended field-radiotherapy (EF-RT) or (ARM B) 30 Gy TD EF-RT plus 10 Gy TD involved field-radiotherapy (IF-RT), both arms without any chemotherapy. Three hundred sixty-six of these patients were evaluable for early and long-term response, such as remission status, freedom from treatment failure (FFTF), and overall survival (OAS). For quality control, all planning and verification films as well as dose charts were prospectively reviewed by a panel of four experts, all heads of a radiotherapy department, where protocol violations (PV) were seen either with regard to errors in treatment technique, treatment volume, in TD and/or in dose/time-relationship. RESULTS: Treatment resulted in a complete remission (CR) of 98%; in a 5-year FFTF of 76%, and a 5-year OAS of 97%. There was no difference between the two arms in favor of 40 Gy EF compared to 30 Gy EF regarding FFTF and OAS, without any in field relapse throughout the EF volumes. Expectedly, 5-years FFTF was significantly influenced by the quality of radiotherapeutical procedures: 70% with protocol violations (PV) vs. 82% without PV. CONCLUSION: Subclinical involvement in ESHD without risk factors is sufficiently treated by a TD of 30 Gy without chemotherapy, leading to a 5-years FFTF of 82% and a 5-year OAS of 97% in a multicenter treatment setting, where quality assurance is mandatory.

Adolescent↗
PubMed1996

[Radiotherapy of lymphogranulomatosis in adulthood].

Hodgkin's disease is a highly curable disease. In clinical stages I to II (A and B) of Hodgkin's disease radiotherapy alone is curative in more than 80% of the patients. Challenges remain, however, to further refine our therapy, identify and cure the minority of patients who continue to succumb to this disease. Innovative therapies or significant modifications of current standard therapies are very much needed. The sequential approach of drugs and radiation therapy could reduce the length (not the dose!) of primary chemotherapy as well as the extent and the dose of additive radiation. An effective polydrug regimen not including alkylating agents may avoid the risk of infertility and second malignancies. In patients with Hodgkin's disease presenting with massive mediastinal involvement the efficacy of combined modality therapy has been proven by all research groups. In patients with clinical stage III (A and B) as well as selected stage IV Hodgkin's disease the percentage of nodal relapse is not negligible even after a very effective chemotherapy. Radiotherapy limited to the initial site(s) of bulky lymphoma is not enough to avoid the risk of nodal relapse in adjacent nodal areas. And here, too, avoiding the administration of alkylating agents may drastically reduce some of the serious long-term toxicities.

Antineoplastic Combined Chemotherapy Protocols↗