Biomedical subjects

H Geinitz

Publications and source records attributed to H Geinitz.

9 recordsLinked to original sources

PubMed2006

beta1-integrin-mediated signaling essentially contributes to cell survival after radiation-induced genotoxic injury.

Integrin-mediated adhesion to extracellular matrix proteins confers resistance to radiation- or drug-induced genotoxic injury. To analyse the underlying mechanisms specific for beta1-integrins, wild-type beta1A-integrin-expressing GD25beta1A cells were compared to GD25beta1B cells, which express signaling-incompetent beta1B variants. Cells grown on fibronectin, collagen-III, beta1-integrin-IgG or poly-l-lysine were exposed to 0-6 Gy X-rays in presence or depletion of growth factors and phosphatidylinositol-3 kinase (PI3K) inhibitors (LY294002, wortmannin). In order to test the relevance of these findings in tumor cells, human A-172 glioma cells were examined under the same conditions after siRNA-mediated silencing of beta1-integrins. We found that beta1A-integrin-mediated adhesion to fibronectin, collagen-III or beta1-IgG was essential for cell survival after radiation-induced genotoxic injury. Mediated by PI3K, pro-survival beta1A-integrin/Akt signaling was critically involved in this process. Additionally, the beta1-integrin downstream targets p130Cas and paxillin-impaired survival-regulating PI3K-dependent JNK. In A-172 glioma cells, beta1-integrin knockdown and PI3K inhibition confirmed the central role of beta1-integrins in Akt- and p130Cas/paxillin-mediated prosurvival signaling. These findings suggest beta1-integrins as critical regulators of cell survival after radiation-induced genotoxic injury. Elucidation of the molecular circuitry of prosurvival beta1-integrin-mediated signaling in tumor cells may promote the development of innovative molecular-targeted therapeutic antitumor strategies.

Animals↗

PubMed2004

[Radiotherapy in the elderly].

Radiotherapy in curative or palliative intent is well tolerated and effective in the elderly patient, too. When establishing the indication for treatment, the extent of concomitant diseases, the general state of health of the patient, and his/her life expectancy must all be taken into account. When extensive volumes in the head/neck, chest or abdominal areas need to be irradiated, adequate uptake of fluid and calories must be ensured, and electrolytes, renal parameters and the blood count must be closely monitored. Supporting measures should be applied early on.

Age Factors↗

PubMed2001

Fatigue, serum cytokine levels, and blood cell counts during radiotherapy of patients with breast cancer.

PURPOSE: To assess the level of fatigue during the course of adjuvant radiotherapy (RT) of breast cancer patients and its relation to anxiety, depression, serum cytokines, and blood count levels. METHODS AND MATERIALS: Forty-one patients who received adjuvant RT after breast-conserving surgery were prospectively studied. All patients underwent RT without concomitant chemotherapy. Patients rated their fatigue with two standardized self-assessment instruments, the Fatigue Assessment Questionnaire and a visual analog scale on fatigue intensity, before RT, during weeks 1-5 of RT, and 2 months after RT completion. In addition, the anxiety and depression levels were assessed with the Hospital Anxiety and Depression Scale. A differential blood cell count and the serum levels of the cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha were determined in parallel to the fatigue assessments. RESULTS: Fatigue intensity as assessed with the visual analog scale increased (p <0.001) until treatment week 4 and remained elevated until week 5. Two months after RT, the values had fallen to the pretreatment levels. Fatigue measured with the Fatigue Assessment Questionnaire did not increase significantly during treatment, but the subscores on physical (p = 0.035) and cognitive (p = 0.015) fatigue were elevated during treatment weeks 4 and 5. Affective fatigue did not change significantly. Anxiety, as rated with the Hospital Anxiety and Depression Scale, declined during RT (p = 0.002), but the Hospital Anxiety and Depression Scale depression score did not change significantly. IL-1beta, IL-6, and tumor necrosis factor-alpha levels did not change during therapy and did not correlate with fatigue. Peripheral blood cell levels declined significantly during therapy and were still low 2 months after treatment. Until treatment week 5, lymphocytes were reduced to almost 50% of their initial values. Hemoglobin levels did not correlate with fatigue. CONCLUSIONS: We observed an increase in fatigue during adjuvant RT of patients with breast cancer. Fatigue returned to pretreatment levels 2 months after treatment. No evidence was found that anxiety, depression, serum levels of IL-1beta, IL-6, tumor necrosis factor-alpha, or declining hemoglobin levels were responsible for the treatment-induced fatigue.

Adult↗

PubMed2001

[Radiotherapy of prostate carcinoma].

As well as radical prostatectomy external body radiotherapy (EBRT) offers the chance of cure in non-metastasized prostate cancer. With total doses of 70 Gy or more, conventional fractionated RT can achieve 2-years biological no-evidence of disease (bNED) of more than 90% and about 50% in tumor stages with low and medium risk of metastases respectively. In early stages (T 1-2 Nx) recurrence free survival is after ten years 43-76%, in T1b-T2 pNO stages it is about 90% and comparable to those after radical prostatectomy. In T3-tumors recurrence free survival is from 32-42%. In randomized studies an advantage of conformal to conventional planned EBRT could be impressively demonstrated. Severe sequelae of the intestinal and urogenital tract could be seen in less than 5%, of treated patients. The value of combined hormonal and radiation therapy is not yet cleared. In early stages results by pure EBRT are convincing so that hormonal therapy might be superfluous. In locally advanced stages a preceding hormonal therapy might decrease the tumor volume by reducing the tumor cell load and, therefore, reduce the conformally irradiated volume. The irradiation of the pelvic or abdominal lymphatic drainage did not improve overall survival in published studies so far though improving the locoregional tumor control rates. Due to the large irradiated volume and simple radiation techniques sequelae were impressively increased. A participation in running national or international studies to clarify the value of postoperative EBRT, RT of pelvic lymph nodes, dose escalation and combined hormonal and radiation therapy will be reasonable.

Dose Fractionation, Radiation↗

PubMed2000

Daily CT planning during boost irradiation of prostate cancer. Feasibility and time requirements.

BACKGROUND: In the irradiation of prostate cancer internal organ movement leads to uncertainties in the daily localization of the clinical target volume. Therefore more or less large safety margins are added when designing the treatment portals. With daily CT planning internal organ movement can be compensated to some extent, safety margins can be reduced and irradiated normal tissue can be spared. The feasibility of daily CT-based 3D treatment planning is studied in a patient with localized prostate carcinoma using a new patient positioning system. METHODS: Daily CT planning was applied during boost irradiation of a patient with prostate cancer: After patient immobilization the pelvis was scanned in 3 mm CT slices. Planning was done with the BrainSCAN planning system for stereotactic body irradiation. The prostate was contoured in all slices and the safety margins of the micromultileafs were automatically set to the distance chosen by the physician (0.8 cm). Patient positioning was done with the BrainLAB ExacTrac positioning system on the basis of skin attached stereotactic body markers. Before each treatment verification images of the isocenter were taken. RESULTS: The total time requirement for planning and irradiation was about 1 hour 15 minutes. Patient positioning on the treatment couch took about 10 minutes. The accuracy of the positioning system was good (75% of the deviations were smaller than 3 mm). The shift of the single markers from CT scan to CT scan was more extensive than those of the center of all 7 markers combined (47% of the deviations were smaller than 3 mm). The location of the markers seems to influence the magnitude of their dislocation. CONCLUSION: Daily CT planning is feasible but time consuming. The new patient positioning system ExacTrac is an interesting tool especially for daily CT planning since conventional simulation can be omitted.

Aged↗

PubMed2000

[Prostatic carcinoma: problems in the interpretation of rectal dose-volume histograms].

BACKGROUND: Dose-volume histograms (DVHs) are used for the prediction and calculation of late radiation side effects. In literature the predictive value of rectal DVHs is controversially discussed. Differences in contouring might contribute to the contradicting results. In particular the cranial and caudal border of the contoured organ are not uniformly defined. PATIENTS AND METHODS: The DVHs of 12 patients who were treated with conformal radiotherapy for prostate cancer were investigated. Six of the patients suffered from mild rectal bleeding as a late side effect of radiotherapy. Six patients without rectal bleeding (minimal follow-up 30 months) matched for age, concomitant disease and treatment concept served as controls. Four different DVHs with 4 different definitions of the cranial and caudal rectal border were generated for each patient. For each of the 48 DVHs the percent volume fractions (V50, V80, V95) and absolute volume fractions (aV50, aV80, aV95) were calculated that received more than 50%, 80% and 95% of the reference dose. RESULTS: For every patient there were considerable variations in the volume fractions depending on the definition of the rectum borders (Table 1). The mean and median values of the percent and absolute volume fractions of the bleeding patients were higher than those of the non-bleeders no matter how the rectum borders were defined. None of the volume fractions could totally separate bleeding from non-bleeding patients. CONCLUSION: There is a high variability of absolute and percent volume fractions of rectal DVHs depending on how the rectal borders were defined. For the comparison and for the interpretation of rectal DVHs a uniform definition would be helpful.

Aged↗

PubMed1999

[Radiotherapy of the elderly patient. Radiotherapy tolerance and results in older patients].

BACKGROUND: Despite a growing number of elderly patients receiving radiation therapy little is known about side effects and outcome of irradiation in this section of the population. METHODS: In a review article epidemiologic data, aspects of radiation-biology as well as side effects and outcome of radiation therapy of elderly patients are discussed. RESULTS: Cancer incidence rises with age (Figure 1) and is exceeding 3.5% for males older than 85 years. With a life expectancy of more than 4 years, curative therapy is indicated even at this age. Furthermore several retrospective studies indicate that local control and disease-Specific survival after radiation therapy of elderly patients is comparable with that of younger persons (Tables 3 and 4). The exception contains elderly patients with Grade-III to IV gliomas or with rectal carcinoma who show a reduced survival which is perhaps caused by less aggressive combined treatment (tumor resection). Although some biological and molecular data indicate a rise in radiation sensitivity with growing age like the reduction of the capacity of some DNA-repair enzymes, there is no convincing evidence in animal studies or in retrospective clinical studies that radiation therapy is generally less well tolerated by older individuals (Tables 1 and 2). Some age-depending differences in organ toxicities are described in 3 large studies, which evaluate the data of patients who were enrolled in different EORTC-trials: Older patients suffer more of functional mucositis in case of radiation therapy to the head and neck, they have an increased weight loss and a higher frequency of late esophageal damage when irradiated in the thorax, and they show a higher prevalence of sexual dysfunction when treated with radiation therapy to the pelvis. On the other hand younger patients suffer more from acute toxicity like skin damage, nausea, and deterioration of the performance status during pelvic radiotherapy. When discussing the dose intensity of radiation therapy concomitant disease which leads to extensive atherosclerotic vessel damage should be kept in mind. Old patients should be monitored closely during therapy, since the loss of electrolytes or fluid is often not very well tolerated. CONCLUSION: The indication to radiation therapy of elderly cancer patients should take into account their performance status as well as the extent and the severity of comorbidity. Age per se is seldom a contraindication for radiation therapy. Regarding the available data in literature there is no indication for a dose reduction in radiation therapy only because of age, especially in the curative setting.

Aged↗

PubMed1998

Therapy and prophylaxis of acute and late radiation-induced sequelae of the esophagus.

BACKGROUND: Radiation-induced esophagitis is a frequent acute side effect in curative and palliative radiotherapy of thoracal and cervical tumors. Late reactions are rare but might be severe. METHODS: A research for reports on prophylactic and supportive therapies of radiation-induced esophagitis was performed (Medline, Cancerlit, and others). RESULTS: Nutrition must be ensured and symptomatic relief of sequelae is important, especially in the case of dysphagia. The latter can be improved by topic or systemic analgetics. If esophageal spasm occurs, calcium antagonists might help. In case of gastro-esophageal reflux proton pump inhibitors should be used. There is no effective prophylactic measure for radiation esophagitis. Late side effects with clinical relevance are rare in conventional radiotherapy. Chronic ulcera, fistula or stenosis may develop. Before any treatment, a tumor infiltration of the esophagus should be excluded by biopsy. This can lead more often to late complications than radiation therapy itself. Nutrition should be ensured by endoscopic dilation, stent-implantation, or endoscopic percutaneous gastrostomy. Local injection of steroids might be used to avoid an early restenosis. CONCLUSIONS: An intensive symptomatic therapy of acute esophagitis is reasonable. Effective prophylaxis do not exist. Late radiation induced sequelae is rare. Therefore, a tumor recurrence should be excluded in cases of dysphagia. Securing nutrition by PEG, stent, or port is well in the fore.

Amifostine↗

PubMed1997

Radiotherapy in the aged.

Radiation therapy fulfills all the requirements to be used with curative or palliative intent in nearly every case of cancer in the elderly. Radiotherapy is not associated with acute mortality in older persons and can permit organ and tissue preservation. The modern modalities to deliver radiotherapy treatment permit a large sparing of normal tissues. We need major information on proliferative activity of normal tissues and cancer in the elderly, on results according to stage of tumors, and on acute and late sequelae according to performance status of the patient. It is mandatory to perform prospective studies in order to work out protocols for oncologic treatments and specifically for radiotherapy, to treat adequately an increasing part of population.

Age Factors↗