PubMed Health⌕ Search

Biomedical subjects

Peter Vaupel

Publications and source records attributed to Peter Vaupel.

At least 37 records · Page 2Linked to original sources
PubMed2004

The impact of treatment for genital cancer on quality of life and body image--results of a prospective longitudinal 10-year study.

OBJECTIVE: To evaluate the impact of treatment for genital cancer on quality of life and body image to determine patients' therapy-related needs for quality improvement of medical care before and after surgery. METHODS: We started to evaluate women with cervical cancer planned for pelvic exenteration in 1993 and integrated women planned for a Wertheim-Meigs surgery in 1995 before surgery, 4 and 12 months after surgery. Thanks to funding since 1999, more than 400 patients with a diagnosis of genital (n = 185) or breast (n = 217) cancer participated in this prospective study until July 2003. In this paper, we will focus on n = 129 women with cervical cancer. The assessment protocol included objective questionnaires for quality of life and body image (CARES; EORTC; Body image by Strauss and Appelt). The evaluation of quality of life incorporated five dimensions: physical and psychosocial health, marital and sexual status, and medical interaction. RESULTS: Before surgery, women with a Wertheim's procedure indicated significantly less problems concerning the quality of life global score (P = 0.002) and several subscales compared to women with a pelvic exenteration. After surgery, both groups indicated their sexual problems to be the greatest restriction in terms of quality of life, especially in women with non-reconstructive surgery as well as in women with adjuvant radio and/or chemotherapy. Concerning body image, attractiveness or self-confidence was significantly reduced postoperatively compared to the preoperative status for both groups (P = 0.000), and also worsened with the extent of treatment. Worries about the patient's family persisted over time and represented the most important item about all questions concerning quality of life as well as the fear of recurrence. CONCLUSION: This on-going study demonstrates the interferences between the treatment modality and the patient's quality of life, especially about sexuality and body image. Our results suggest not only to provide reconstructive surgery if possible, but also to integrate psychosocial information aspects on future quality of life outcome before surgery as well as to offer psychosocial support related to the extent of treatment modality after surgery.

Adult↗
PubMed2004

The role of hypoxia-induced factors in tumor progression.

Hypoxia is a common characteristic of locally advanced solid tumors that has been associated with diminished therapeutic response and, more recently, with malignant progression, that is, an increasing probability of recurrence, locoregional spread, and distant metastasis. Emerging evidence indicates that the effect of hypoxia on malignant progression is mediated by a series of hypoxia-induced proteomic and genomic changes activating angiogenesis, anaerobic metabolism, and other processes that enable tumor cells to survive or escape their oxygen-deficient environment. The transcription factor hypoxia-inducible factor 1 (HIF-1) is a major regulator of tumor cell adaptation to hypoxic stress. Tumor cells with proteomic and genomic changes favoring survival under hypoxic conditions will proliferate, thereby further aggravating the hypoxia. The selection and expansion of new (and more aggressive) clones, which eventually become the dominant tumor cell type, lead to the establishment of a vicious circle of hypoxia and malignant progression.

Cell Hypoxia↗
PubMed2004

Tumor hypoxia: causative factors, compensatory mechanisms, and cellular response.

Hypoxia is a characteristic feature of locally advanced solid tumors resulting from an imbalance between oxygen (O(2)) supply and consumption. Major causative factors of tumor hypoxia are abnormal structure and function of the microvessels supplying the tumor, increased diffusion distances between the nutritive blood vessels and the tumor cells, and reduced O(2) transport capacity of the blood due to the presence of disease- or treatment-related anemia. Tumor hypoxia is a therapeutic concern since it can reduce the effectiveness of radiotherapy, some O(2)-dependent cytotoxic agents, and photodynamic therapy. Tumor hypoxia can also negatively impact therapeutic outcome by inducing changes in the proteome and genome of neoplastic cells that further survival and malignant progression by enabling the cells to overcome nutritive deprivation or to escape their hostile environment. The selection and clonal expansion of these favorably altered cells further aggravate tumor hypoxia and support a vicious circle of increasing hypoxia and malignant progression while concurrently promoting the development of more treatment-resistant disease. This pattern of malignant progression, coupled with the demonstration of a relationship between falling hemoglobin level and worsening tumor oxygenation, highlights the need for effective treatment of anemia as one approach for correcting anemic hypoxia in tumors, and in so doing, possibly improving therapeutic response.

Adaptation, Physiological↗
PubMed2004

Perfusion, oxygenation status and growth of experimental tumors upon photodynamic therapy with Pd-bacteriopheophorbide.

The aim of this study was to assess the anti-tumor effect of photodynamic therapy (PDT) using a novel bacteriochlorophyll derivative, palladium-bacteriopheophorbide (TOOKAD) on tumor growth, perfusion and oxygenation. Rat DS-sarcomas were treated with either TOOKAD-PDT (2 mg/kg, i.v., immediate illumination) or one of the control treatments (sham-treatment, illumination without photosensitizer, or photosensitizer without illumination). The light source was an infrared-A irradiator fitted with appropriate filters, so that the wavelengths applied (665-800 nm) included the absorption maximum of TOOKAD at 763 nm. Tumor volume was monitored for 90 days after treatment or until a target volume (3.5 ml) was reached. TOOKAD-PDT dramatically inhibited tumor growth with 92% of tumors not reaching the target volume within the observation period. In further experiments, tumor perfusion was assessed using laser Doppler flowmetry. Upon TOOKAD-PDT treatment, a rapid, pronounced decrease in perfusion was seen, down to levels corresponding to only 3% of initial values. Tumor oxygenation monitoring revealed parallel decreases, with levels corresponding to anoxia being reached. The significant anti-tumor effects presented in this report, taken together with the chemical and pharmacokinetic properties of the novel photosensitizer TOOKAD, underline the therapeutic potential of this approach in which flow stasis and induction of anoxia are key elements.

Animals↗
PubMed2003

Intensified oxidative and nitrosative stress following combined ALA-based photodynamic therapy and local hyperthermia in rat tumors.

Oxidative stress-related changes in tumors upon localized hyperthermia (HT), 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) and their combination (ALA+HT) were examined after the observation that the antitumor effects of ALA-PDT could be significantly enhanced upon simultaneous application of HT. Rats bearing s.c. DS-sarcomas (0.6-1.0 ml) on the hind foot dorsum were anesthetized and underwent one of the following treatments: (i) ALA-PDT (375 mg/kg 5-ALA i.v.); (ii) localized HT, 43 degrees C for 60 min; (iii) combined ALA-PDT and HT [=ALA+HT]. Appropriate control experiments were also performed. After treatment, tumors were excised and rapidly frozen for later analysis of nitrosative stress (protein nitration), apoptotic events (TUNEL, caspase activation, DNA and RNA fragmentation), expression of heat shock proteins (hsp70 and HO-1), glutathione (GSH) levels and glutathione peroxidase (GPx) activity. Protein nitration was found to increase upon treatment, being especially pronounced in the ALA+HT group, and could partially be related to areas surrounding microvessels. The extent of nitrosative stress also correlated well with the appearance of the markers of apoptosis and the inhibition of in vivo tumor growth as seen in a previous study. GSH levels decreased upon treatment, the reduction being most prominent in the ALA-PDT and ALA+HT groups. GPx activity, however, showed a significant decrease only in the ALA-PDT group. Whereas hsp70 expression increased upon HT, ALA-PDT caused a decrease, and these opposing effects were nullified with ALA+HT. The results obtained point to a number of cellular mechanisms-including effects on cellular defense mechanisms and an abrogation of the heat shock defense mechanism-that may interact to achieve the potentiated tumor response rate seen in vivo upon combined treatment.

Aminolevulinic Acid↗
PubMed2003

Oxygenation gain factor: a novel parameter characterizing the association between hemoglobin level and the oxygenation status of breast cancers.

Tumor hypoxia has been linked to acquired treatment resistance, tumor progression, and poor prognosis. Because anemia is a major causative factor for the development of hypoxia, the association between blood hemoglobin concentration (cHb) and breast cancer oxygenation was examined in this study. In addition, a novel parameter characterizing the relationship between oxygenation status and rising cHb is introduced: the oxygenation gain factor (OGF). In breast cancer patients, median cHb over the range 8.5-14.7 g/dl correlated positively with the median pO(2) (3-15 mm Hg), yielding an average OGF of 2 mm Hg.dl/g. In contrast, in normal tissues (normal breast, subcutis, and skeletal muscle) the median pO(2) values were substantially higher (52 mm Hg, 51 mm Hg, and 37 mm Hg, respectively) and remained constant irrespective of the hemoglobin level over the range from 10 to 16 g/dl (OGF = 0 in grade I anemia and nonanemic patients). Moderately lower median pO(2) values in subcutis and skeletal muscle were only observed in grade II anemia (8 g/dl < cHb < or =10 g/dl), although this would appear to be of no biological relevance. Conversely, in breast cancers, even mild anemia (grade I anemia) is a major causative factor for the development of hypoxia or anoxia.

Adult↗
PubMed2003

Impact of oxygenation status and patient age on DNA content in cancers of the uterine cervix.

PURPOSE: In carcinomas of the uterine cervix, the tumor oxygenation status has been shown to be a prognostic indicator that is independent of treatment modality. In vitro studies suggest gene amplification and polyploidization to be among the major consequences of hypoxia (with or without consecutive reoxygenation) and to be associated with treatment resistance and tumor progression. This study analyzed whether hypoxia alters net DNA content in uterine cervix cancer cells to the extent that it is identifiable by DNA image cytometry. MATERIALS AND METHODS: In 64 patients with primary cervical cancer, tumor oxygenation was assessed polarographically and correlated with cell DNA content (DNA image cytometry) in areas adjacent to the oxygen microsensor tracks in which oxygenation measurements were made. RESULTS: No correlation between DNA content (stemline position, Auer classification, and 2c deviation index) and oxygenation status was observed. However, an association between DNA content and patient age and menopausal status was found. CONCLUSION: Using DNA cytometry, hypoxia-associated genomic changes in uterine cervix cancer cells could not be detected. The impact of tumor hypoxia on the genome may be masked by the effects of alternative mechanisms of genomic instability that can also influence DNA content.

Adult↗
PubMed2003

Erythropoietin restores the anemia-induced reduction in radiosensitivity of experimental human tumors in nude mice.

PURPOSE: The effect of recombinant human erythropoietin (rhEPO) on the radiosensitivity of human tumor xenografts growing in anemic and nonanemic nude mice was studied. METHODS AND MATERIALS: Anemia was induced by total body irradiation ([TBI], 2 x 4 Gy) of mice before tumor implantation into the subcutis of the hind leg. The development of anemia was prevented by rhEPO (750 U/kg s.c.) given 3 times weekly starting 2 weeks before TBI. Fourteen days after fractionated TBI (tumor volume of approx. 40 mm(3)), single-dose irradiation of the tumor with varying doses was performed so that in full dose-response relationship for the probability of tumor cure was obtained. RESULTS: Radiation-induced anemia (hemoglobin concentration [cHb] = 9.9 g/dl) led to a reduced radiosensitivity compared to controls [49.4 vs. 40.1 Gy radiation dose to control 50% of the tumors (TCD50)]. Upon rhEPO treatment for anemia prevention (cHb = 13.3 g/dl), the TCD50 was 39.8 Gy, illustrating restored radiosensitivity compared to anemic mice. CONCLUSION: These data provide further experimental evidence for restored radiosensitivity upon prevention of anemia with rhEPO.

Anemia↗
PubMed2003

Microcirculatory function, tissue oxygenation, microregional redox status and ATP distribution in tumors upon localized infrared-A-hyperthermia at 42 degrees C.

Since local hyperthermia (HT) affects microenvironmental parameters, the aim of the study was to analyze the impact of 42 degrees C-HT on microcirculatory function, tumor pO2, microregional redox status and ATP distribution in experimental rat tumors. Subcutaneously growing DS-sarcomas were treated with localized HT using infrared-A radiation resulting in a mean tumor temperature of 42 degrees C. The relative red blood cell (RBC) flux in the tumor was assessed using the laser Doppler technique and the mean tumor pO2 measured continuously using O2-sensitive catheter electrodes. In a second series of experiments, the microregional distribution of the mitochondrial redox status and ATP concentration was measured. Although the average RBC flux increased by 63%, tumor pO2 rose only by approx. 6%. No distinct changes were seen in the mitochondrial redox status. The microregional distribution of the redox status as well as of the ATP concentration showed considerable heterogeneity. In conclusion, although 42 degrees C-HT leads to a distinct improvement in tumor perfusion, there is practically no change in the oxygenation status. The latter finding can be explained by an equivalent increase in the oxygen consumption rate of the cells which increases by approx. 58% at 42 degrees C compared to normothermia.

Adenosine Triphosphate↗
PubMed2003

Oxygenation status of cervical carcinomas before and during spinal anesthesia for application of brachytherapy.

BACKGROUND AND PURPOSE: To date, no information is available concerning the impact of spinal anesthesia on the oxygenation status of carcinomas of the uterine cervix. The aim of this study was therefore to determine the influence of spinal anesthesia on the oxygenation status of cervical carcinomas. PATIENTS AND METHODS: In ten patients with cervical carcinoma who received spinal anesthesia for a first application of brachytherapy, intratumoral pO2 measurements (pO2 histography system, Eppendorf-Netheler-Hinz, Hamburg, Germany) were performed. Systemic parameters were documented prior to and during spinal anesthesia. Patients breathed room air spontaneously. For further evaluation, all intratumoral pO2 values were pooled, and overall median pO2 values and fractions of hypoxic pO2 values < or = 5 mmHg were calculated. Overall median pO2 values in the subcutis were also calculated. RESULTS: There were no significant changes of systemic parameters, median subcutaneous pO2 values, median intratumoral pO2 values, and the fractions of hypoxic pO2 values < or = 5 mmHg in the tumor upon administration of spinal anesthesia. The variability of measured pO2 values increased during spinal anesthesia, although substantial changes in the oxygenation status were only seen in individual cases (n = 2). CONCLUSION: This study shows for the first time that the oxygenation status of cervical carcinomas, in general, is not influenced by spinal anesthesia prior to application of brachytherapy. To conclude, the data presented suggest that reliable pO2 measurements can be performed under spinal anesthesia. At the same time, since no substantial changes in tumor oxygenation were observed, spinal anesthesia should not affect the O2-related efficacy of high-dose-rate brachytherapy.

Adenocarcinoma↗
PubMed2003

Impact of anemia prevention by recombinant human erythropoietin on the sensitivity of xenografted glioblastomas to fractionated irradiation.

BACKGROUND: Pronounced oxygen deficiency in tumors which might be caused by a diminished oxygen transport capacity of the blood (e.g., in anemia) reduces the efficacy of ionizing radiation. The aim of this study was to analyze whether anemia prevention by recombinant human erythropoietin (rHuEPO) affects the radiosensitivity of human glioblastoma xenografts during fractionated irradiation. MATERIAL AND METHODS: Anemia was induced by total body irradiation (TBI, 2 x 4 Gy) of mice prior to tumor implantation into the subcuts of the hind leg. In one experimental group, the development of anemia was prevented by rHuEPO (750 U/kg s.c.) given three times weekly starting 10 days prior to TBI. 13 days after tumor implantation (tumor volume approx. 40 mm3), fractionated irradiation (4 x 7 Gy, one daily fraction) of the glioblastomas was performed resulting in a growth delay with subsequent regrowth of the tumors. RESULTS: Compared to nonanemic control animals (hemoglobin concentration cHb = 14.7 g/dl), the growth delay in anemic mice (cHb = 9.9 g/dl) was significantly shorter (49 +/- 5 days vs. 79 +/- 4 days to reach four times the initial tumor volume) upon fractionated radiation. The prevention of anemia by rHuEPO treatment (cHb = 13.3 g/dl) resulted in a significantly prolonged growth delay (61 +/- 5 days) compared to the anemia group, even though the growth inhibition found in control animals was not completely achieved. CONCLUSIONS: These data indicate that moderate anemia significantly reduces the efficacy of radiotherapy. Prevention of anemia with rHuEPO partially restores the radiosensitivity of xenografted glioblastomas to fractionated irradiation.

Anemia↗
PubMed2003

O(2) extraction is a key parameter determining the oxygenation status of malignant tumors and normal tissues.

The aim of this study was to assess pivotal factors determining the oxygenation status of malignant tumors, and, for comparison, of normal tissues. For this purpose, microvascular patterns, blood flow data, O2 consumption rates and O2 extractions were correlated to the median pO2 values of isografted rodent and xenografted human tumors, and of various normal tissues. No correlations were found between median pO2 values and vascular patterns, O2 consumption rate or blood flow rate. When O2 extraction, however, was considered (a comprehensive parameter which encompasses all of the above factors), a strong inverse correlation was found between this parameter and the median pO2 values, both for malignant tumors (r2=0.917) and normal tissues (r2=0.959). At similar O2 extraction values, the median pO2 values in the solid tumors were substantially lower than those in normal tissues, a finding which most probably reflects the chaotic microcirculation found in tumors, the loss of flow regulation which in normal tissues meets the metabolic demands of the cells, and in some cases, tumor-associated anemia.

Animals↗