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R Sauer

Publications and source records attributed to R Sauer.

At least 55 records · Page 3Linked to original sources
PubMed1999

Interaction of paclitaxel (Taxol) and irradiation. In-vitro differences between tumor and fibroblastic cells.

AIM: Optimal dose and schedule of paclitaxel in combined drug-irradiation treatment could not be determined for most of tumors yet. The aim of this study was to compare in vitro cytotoxicity and radiosensitizing abilities as a function of single paclitaxel (Taxol) exposure in tumor and fibroblastic cells using different drug incubation irradiation intervals. MATERIAL AND METHOD: A lung-carcinoma (SK-LU-1), glioblastoma (U-138 MG) and rodent fibroblast cell line (HyB14FAF28) were used. The clonogenic assay was applied for survival investigation. alpha beta-values were calculated using the linear-quadratic model (log S = -alpha D - beta D2). Cytotoxicity of Taxol was examined at 0 to 50 microM. Combined Taxol-radiotherapy exposure was accomplished with 10 microM Taxol plus 10 Gy irradiation (RT) following after a 1-hour and 9-hour interval. For controls cells were exposed to Cremophor EL/ethanol (CEL/eth) and a phosphate buffered saline (PBS). RESULTS: Single Taxol exposure (10 microM) resulted in 0.54/0.50/0.84 (3-hours incubation) and 0.094/0.48/0.82 (15-hours incubation) survival of SK-LU-1, U-138 MG and HyB14FAF28 cells, respectively. Taxol concentrations from 2 to 50 microM only had cytotoxic effect in tumor cells. Single dose RT (10 Gy) led to cell survival of 0.0006/0.006/0.03. The diluent CEL/eth also showed cytotoxic activity. Taxol plus RT led to cell survival of 0.00025/0.0014/0.042 (1 hour) and 0.0004/0.0019/0.04 (9 hours) without significant difference between chosen time intervals. alpha beta-values showed great variation lacking evidence for definite radiosensitization. alpha increase after Taxol and alpha decrease after CEL/eth exposure were detected. CONCLUSIONS: The data presented demonstrate a potential beneficial effect, described as co-operation, by combining Taxol and RT in human tumor cells and rodent fibroblasts. High intrinsic alpha components of the tumor cells as well as CEL/eth's antagonizing actions could be likely to disturb and influence paclitaxel's abilities leading to radiosensitization.

Adenocarcinoma↗
PubMed1999

Effect of amifostine (Ethyol) on the development of extraembryonic blood vessels in chick embryos.

AIM: Systemic and local side effects can limit radio- as well as chemotherapy in patients suffering from neoplastic diseases. One possibility to reduce the therapy-dependent side effects is to attenuate radical induced alterations of normal healthy tissue by application of antioxidants. Preclinical and clinical studies demonstrated the ability of amifostine to protect normal, but not neoplastic, tissues from cytotoxic effects of chemotherapy or irradiation. The purpose of the present study was to establish whether amifostine (Ethyol) can affect microvessel density in vivo. MATERIAL AND METHODS: For this study fertilized crossbred "White-Plymouth-Rocks x Sussex" eggs were used. After 48 hours of incubation 0.05 ml solution containing 25.7 micrograms (approximately 120 microM) amifostine were injected next to the germ disc. Taking into account the mean surface area of the are vasculosa and the embryo, this corresponds to a dose of 26 micrograms/cm2. As controls, the area vasculosa of eggs treated with 0.05 ml NaCl 0.9% were used. Twenty-four and 48 hours after injection of amifostine or NaCl photographs and video microscopic pictures from treated areas and controls were taken and evaluated for vascular density. Results of vascular density are given as vascular intersections per mm2 (VIS/mm2). RESULTS: There was a significant (p < 0.001) difference in vascular density with a mean microvessel count of 30.40 (+/- 12.84 SD) VIS/mm2 in the NaCl control and 53.69 (+/- 24.56 SD) VIS/mm2 in the amifostine-treated area vasculosa. CONCLUSION: The results show that amifostine induced an increase in vascular density in the rapidly proliferating area vasculosa of the early chick embryo.

Amifostine↗
PubMed1999

[Neoadjuvant radiochemotherapy in soft tissue sarcomas. Optimization of local functional tumor control].

BACKGROUND: Adequate local control rates > 90% and acceptable functional results are the paramount goals in the treatment of soft-tissue sarcoma. Purpose of this paper is to evaluate response, long-term control, functional outcome and toxicity following neoadjuvant radiochemotherapy (RCT) in advanced and recurrent soft tissue sarcoma. PATIENTS AND METHODS: Between 1992 and 1998, a total of 23 patients in whom primary curative limb and function sparing surgery seemed impossible entered the study. Sixteen patients had primary and 7 patients recurrent sarcoma. The stages according to AJCC/UICC 1997 were as follows: rIA (2), rIIA (5) IIA (4), IIB (2), III (7), IV (3). RCT consisted of an accelerated split-course radiation (1.5 to 1.6 Gy twice daily, median total dose 60 Gy, range 60 to 64 Gy, break of 1 week after 30 Gy) with concomitant chemotherapy using adriamycin (50 mg/m2/d on days 2 and 30) and ifosfamide (1.5 g/m2/d on days 1 to 5, 29 to 33). Median follow-up was 26 months (range 2 to 92 months). RESULTS: Twenty-two patients underwent surgery with a curative (R0) resection being achieved in 20/22 (91%) patients and gross residual (R2) tumor or unclear tumor margins (RX) in 1 patient, respectively. Effective tumor-downstaging was documented in 4/22 (18%) patients (ypT0: 3 patients, ypT1: 1 patient). Long-term local tumor control after R0/RX resection remained 100%. Without prognostic impact on tumor response and local control have been the variables primary vs. recurrent tumor, grading, stage and gender. Delayed wound healing was only noted in 1/22 (5%) patients. Four patients developed distant metastases. Overall-, NED- and distant-metastases-free survival rates were 83%, 64% and 68%, respectively, at 3 years. Grade 3/4 neutropenia (WHO) was seen after 21/46 (46%) cycles of chemotherapy with 1 patient dying of septicemia. The functional results were good to excellent in 18/22 (82%) patients. CONCLUSION: Accelerated split-course radiation with 60 to 64 Gy and concurrent chemotherapy using adriamycin/ifosfamide is a safe and effective treatment for soft tissue sarcoma. This regimen may be considered in all cases with recurrent and advanced disease not amenable to primary curative or limb sparing surgery.

Adult↗
PubMed1999

[Locally recurrent and metastatic malignant melanoma. Long-term results and prognostic factors after percutaneous radiotherapy].

PURPOSE: Radiotherapy (RT) is used as last resort for patients with advanced cutaneous malignant melanoma (MM). Herein our 20-year clinical experience is presented analyzing different endpoints and prognostic factors in patients with locally advanced, recurrent or metastatic MM. PATIENTS AND METHODS: From 1977 to 1995, 2,917 consecutive patients were entered in the MM registry of our university hospital. RT was indicated in 121 patients (56 females, 65 males) for palliation in locally advanced recurrent and metastatic MM stages UICC IIB to IV. At the time of RT initiation, 11 patients had primary or recurrent lesions which were either not eligible for surgery or had residual disease (R2) after resection of a primary or recurrent MM lesion (UICC IIB); 57 patients had lymph node (n = 33) or in-transit metastases (n = 24) (UICC III), and 53 had distant organ metastases (7 M1a, 46 M1b) (UICC IV). The time from first diagnosis to on-study RT averaged overall 19 months (median: 18; range: 3 to 186 months). In 77 patients conventional RT and in 44 patients hypofractionted RT was applied with 2 to 6 Gy fractions up to a mean total RT dose of 45 (median: 48; range: 20 to 66) Gy. RESULTS: At 3 months follow-up, complete response (CR) was achieved in 7 (64%), overall response (CR + PR) in all (100%) UICC IIB patients, in 25 (44%) and 44 (77%) of 57 UICC III patients, and in 9 (17%) and 26 (49%) of 53 UICC IV patients. Tumor progression during RT occurred in 25 (21%) patients. Patients with CR survived longer (median: 40 months) than those without CR (median 10 months) (p < 0.01). At the time of evaluation and last FU (December 31, 1996), 26 patients were still alive: 6 (55%) stage UICC IIB, 17 (30%) stage UICC III, and 3 (6%) stage UICC IV patients (p < 0.01). Univariate analysis revealed following prognostic factors for CR and long-term survival: UICC stage (p < 0.001), primary location in the head and neck, total RT dose > 40 Gy (all p < 0.05), while age, gender and primary histological subtype had no impact. In multivariate analysis, UICC stage was the only independent favorable prognostic factor for achievement of CR and long-term survival (p < 0.001). CONCLUSION: External RT provides effective palliation in advanced UICC stages. The UICC staging system is a good predictor of initial and long-term tumor response in metastatic MM. Prospective randomized trials using RT with or without adjuvant therapy for advanced MM are justified.

Adult↗
PubMed1999

[Nasopharyngeal carcinoma: only irradiation or simultaneous radiochemotherapy?].

BACKGROUND: Between 1979 and 1997, a total of 92 patients with primary nasopharyngeal carcinoma were treated at the Hospitals of the University of Erlangen. Until 1988, radiotherapy alone was the treatment of choice and simultaneous radiochemotherapy was consistently applied thereafter. This retrospective analysis was performed to evaluate the influence of concurrent radiochemotherapy on survival and to identify possible prognostic factors on cause-specific survival-, locoregional tumor control- and distant-metastases-free survival rates. PATIENTS AND METHODS: Fifty-three patients (58%) received treatment by radiotherapy alone and 39 (42%) underwent primary radiochemotherapy with 2 courses of 5-FU and cisplatin. Median total dose to the bilateral neck region was 60 Gy (range, 50 to 62 Gy), and 74 Gy (range, 56 to 88 Gy) to the primary tumor. Median follow-up of the surviving patients was 8 years. RESULTS: Following radiochemotherapy and radiotherapy alone, the 5-year-survival rates were 67% and 48%, respectively (p = 0.06). Female patients had a survival advantage as compared to male patients (5-year-survival rate 77% vs 44%, p = 0.01). Patients with and without cranial nerve palsy at presentation had survival rates of 0% and 61%, respectively, at 5 years (p = 0.01). Distant-metastases-free survival was influenced by the following factors: lymph-node involvement (NO: 82% vs N1 to N3: 68%, p = 0.04), gender (female: 88% vs male: 64%, p = 0.01), type of treatment (radiochemotherapy: 86% vs radiotherapy: 63%, p = 0.02) and cranial nerve involvement (76% without and 42% with involvement, p = 0.04). CONCLUSIONS: In primary nasopharyngeal carcinoma simultaneous radiochemotherapy can significantly reduce distant metastases and improve survival as compared to radiotherapy alone. Since late toxicity rates were similar in both treatment groups and the slightly increased acute side effects following radiochemotherapy were effectively compensated by standard supportive care, patients with advanced nasopharyngeal carcinoma may benefit from simultaneous radiochemotherapy.

Adolescent↗
PubMed1999

[Long term results following radiation therapy of locally recurrent and metastatic malignant melanoma].

The 20-year radiotherapy (RT) experience in patients with locally advanced, recurrent or metastatic malignant melanoma (MM) is analyzed with respect to different endpoints and prognostic factors. From 1977 to 1995, 2917 consecutive patients were entered in our MM registry. RT was indicated in 121 patients (56 females, 65 males) for palliation in advanced MM stages. The histology of the primary lesion was nodular in 51, superficial spreading in 35, acral-lentiginous in 8 and lentigo maligna in 4 patients); 22 were missing or could not be reclassified. Eleven patients had primary or recurrent lesions which were ineligible for surgery or had residual disease (R2) after resection of a primary or recurrent lesion (UICC IIB); 57 patients had lymph node (33) or in-transit metastases (24) (UICC III), 53 had distant organ metastases (7 M1a; 46 M1b) (UICC IV). Time from first diagnosis to on-study RT averaged 19 (median: 18; range: 3-186) months. In most cases conventional RT was applied (2-6 Gy single fractions) up to a mean total RT dose of 45 (median: 48; range: 20-66) Gy. At 3 months follow-up (FU), complete response (CR) was achieved in 7 (64%) and overall response (CR+PR) in all (100%) UICC IIB patients, in 25 (44%)/44 (77%) of 57 UICC III patients, and in 9 (17%)/26 (49%) of 53 UICC IV patients. Progression during RT occurred in 25 (21%) patients. Patients with CR survived longer (median: 40 months) than those without CR (median: 10 months) (p<0. 01). At last FU, 26 patients were alive: 6 (55%) UICC IIB, 17 (30%) UICC III, and 3 (6%) UICC IV patients (p<0.01). In univariate analysis following favorable prognostic factors for CR and long-term survival were identified: low UICC stage (p<0.001), primary site head and neck and total dose >40 Gy (all p<0).

Adult↗
PubMed1999

In vitro apoptosis in peripheral blood mononuclear cells induced by low-dose radiotherapy displays a discontinuous dose-dependence.

PURPOSE: Cells undergoing apoptosis contribute to the regulation of activated mononuclear cells (Voll et al. 1997). Low-dose radiotherapy (LD-RT) is known to improve inflammatory symptoms, but the mechanism of action is still unclear. The aim of this study was to investigate the rate of apoptosis of peripheral blood mononuclear cells (PBMC) induced by LD-RT within the therapeutic dose range of anti-inflammatory RT. MATERIALS AND METHODS: PBMC were isolated from venous blood of ten healthy volunteers and were irradiated with single doses between 0.1 and 3.0 Gy. Apoptotic nuclei were detected by flow cytometry after propidium iodide (PI) triton staining, and apoptotic cells were detected by annexin V/PI staining and cell scatter analysis. Since apoptotic cells display increased cytoplasmatic granularity and concomitant reduced cell size, they can be distinguished from viable cells in forward/side scatter (FSC/SSC) histograms. Apoptotic PBMC were further subtyped by double staining with annexin V and directly labelled monoclonal antibodies recognizing the lineage-specific surface markers CD4, CD8, and CD19, respectively. The apoptosis rate of irradiated cells was analysed in a time and dose dependent fashion and was compared to a sham-irradiated control. RESULTS: After irradiation, a dose-dependent increase in apoptosis was observed, with a discontinuity (plateau or peak) between 0.3Gy and 0.7Gy in 9/10 donors (90%) and 59/80 samples (74%). 8/10 donors (80%) and 38/80 samples (47%) showed not only a discontinuous increase with a plateau but a relative maximum of apoptosis peaking within the dose range of 0.3 Gy and up to 0.7 Gy. CONCLUSION: LD-RT induces a relative maximum of apoptosis in PBMC in the does range between 0.3 Gy and 0.7 Gy. This may contribute to its anti-inflammatory effect observed clinically.

Adult↗
PubMed1998

Motor effects induced by a blockade of adenosine A2A receptors in the caudate-putamen.

Motor effects mediated through adenosine A2A receptors within the caudate-putamen were investigated in rats using bilateral microinfusions of MSX-3 (9 microg in 1 microl per side), a water-soluble phosphate prodrug of the selective A2A receptor antagonist MSX-2. Blockade of striatal A2A receptors produced a significant motor stimulation measured by an enhanced sniffing activity. Furthermore, catalepsy induced by systemic dopamine D1 (0.75 mg/kg SCH23390, i.p.) or dopamine D2 receptor blockade (1.5 mg/kg raclopride, i.p.) was potently reversed. These findings suggest that A2A receptors within the caudate-putamen are tonically activated by endogenous adenosine and that a striatal A2A receptor blockade produces motor stimulant effects, in particular in animals with dopamine hypofunction. The present results support the view that A2A receptor antagonists may be potentially useful therapeutics for the treatment of Parkinson's disease.

Animals↗
PubMed1998

Efficacy of radiochemotherapy with platin derivatives compared to radiotherapy alone in organ-sparing treatment of bladder cancer.

PURPOSE: Presently, for muscle-invasive bladder cancer, radical cystectomy is considered to be the standard treatment. Bladder preservation, in the interest of quality of life, is secondary to the primary treatment goal of curing the patient. We present a 14-year multivariate analysis of prognostic factors influencing survival and bladder preservation after transurethral resection of the bladder (TURB) and radiotherapy (RT) +/- chemotherapy. METHODS AND MATERIALS: From May 1982 to May 1996, sequential cohorts of 333 patients with bladder cancer (mean age: 66 years) were treated by either RT alone (128 patients), or with platin-based concomitant radiochemotherapy (RCT, 205 patients) after TURB. Patients (282) with muscle-invasive or T1 high-risk cancers (Grade III, residual tumor after TURB, multifocality, tumor diameter > 5 cm, associated Tis or Ta, multiple recurrences or lymph node metastases), who received a minimal target dose of 45 Gy were selected for analysis (med. follow-up = 7.5 years): after October 1985, 115 patients received cisplatin (25 mg/m2) and 69 patients carboplatin (65 mg/m2) before every treatment fraction (1.8 Gy) on Days 1-5 and 29-33 of conventional fractionated RT. RESULTS: Complete remission rate was 20% (55 of 282 patients) after radical TURB, 57% (56 of 98) after TURB plus postoperative RT, and 80% (145 of 181 patients) after TURB plus RCT (85% after concomitant cisplatin and 70% after RCT plus carboplatin). These differences were significant in multivariate analysis (p = 0.003-0.05). The strongest impact on initial response had T-category (p < 0.0001) and R-status after TURB (p < 0.0003). Cause-specific survival (CSS) was 59 and 43% after 5 and 10 years; 79% of patients survived with preserved bladder. Five-year CSS after RT, RCT-Cis, and RCT-Carbo was 40, 64, and 54%, 10-year CSS 31, 48, and 27%, respectively (p = 0.04-0.045, univariate). R-status after TURB was the only independent prognostic factor for survival and bladder preservation. For relapsed patients after cystectomy, the 5- and 10-year CSS were 40 and 33%. CONCLUSIONS: TURB followed by RT/RCT is an alternative treatment option to primary cystectomy for patients with muscle-invading bladder cancer. Compared to historic controls, the addition of cisplatin or carboplatin leads to significantly more complete remissions and better survival. Survival rates are similar to those achieved by primary cystectomy and possibly even better for selected subjects, such as patients with T3b and T4 tumors. Cystectomy should be restricted to only those patients who fail after RCT.

Adult↗
PubMed1998

Transoral laser surgery of supraglottic cancer: follow-up of 141 patients.

OBJECTIVE: To determine the role of transoral laser resection of supraglottic carcinomas. DESIGN: Retrospective unicenter study of the oncologic results of transoral carbon dioxide laser microsurgery for supraglottic carcinomas performed between February 1979 and December 1993. Median follow-up was 37 months. SETTING: University hospital academic tertiary referral center. PATIENTS: We reviewed the medical records of 141 patients (a consecutive sample of 131 men and 10 women; mean age, 60 years) with histologically proven supraglottic carcinomas undergoing transoral laser surgery, possibly in combination with neck dissection or radiotherapy. Stage distribution of patients was as follows: stage I, 23.4%; stage II, 25.5%; stage III, 16.3%; and stage IV, 34.8% (according to the Union Internationale Contre le Cancer staging system). MAIN OUTCOME MEASURES: Recurrence-free survival rates and local and regional recurrence rates. RESULTS: Five-year recurrence-free survival rates were as follows: the whole case load, 65.7%; stage I, 85.0%; stage II, 62.6%; stage III, 74.2%; and stage IV, 45.3%, according to the Union Internationale Contre le Cancer staging system. The local and regional recurrence rates were 16.3% and 9.9%, respectively. CONCLUSIONS: The oncologic results of transoral carbon dioxide laser surgery are satisfying if clean surgical margins (R0 resection) can be reached. In patients in whom tumor-free margins are not achieved (R1 and R2 resection) and transoral revision is not possible, transcervical procedures (partial or total laryngectomy) should be performed. The indication for transoral supraglottic laryngectomy in T3 lesions should be considered with restraint.

Adult↗
PubMed1998

Schedule-dependent interaction of paclitaxel (Taxol) and irradiation in vitro.

The optimal dose and schedule of paclitaxel in combination with irradiation have not been determined yet. The aim of this study was to compare the in vitro cytotoxicity and enhancement of radiation sensitization as a function of single vs. fractionated paclitaxel exposure. A fibroblast cell line (B14) in exponential growth phase was used. The clonogenic assay was applied to determine cell survival. Flow cytometric measurements were performed to study cell cycle DNA distribution. Cytotoxicity of Taxol was examined at concentrations varying from 2 to 50 microM. Single (1 x 0 microM) vs. fractionated (2 microM/day, days 1-5) exposure of Taxol was investigated. The combination of Taxol plus irradiation as single and fractionated treatment was accomplished with 10 microM Taxol on day 1 plus 10 Gy irradiation on day 1 vs. Taxol 2 microM/day, days 1-5, plus irradiation 2 Gy/day, days 1-5. One-, 9-, and 24-hr intervals between end of incubation and irradiation were defined. Control populations demonstrated an average plating efficiency of 93%. Single Taxol exposure showed an average clonogenic survival of 84%. No significant difference between concentrations varying from 2 to 50 microM was observed. Single dose irradiation (1 x 10 Gy) led to clonogenic survival of 3%. Single exposure of Taxol plus single dose irradiation led to clonogenic survival of 4%. Fractionated radiation showed an average clonogenic survival of 41%. Fractionated Taxol treatment led to an average clonogenic survival of 63%. The combination of fractionated Taxol treatment (2 microM/day, days 1-5) plus fractionated irradiation (2 Gy/day, days 1-5) showed an average clonogenic survival of 15%. No significant difference between the chosen intervals was demonstrated. Flow cytometric measurements did not indicate any significant alterations in cell cycle DNA distribution. In conclusion, the data demonstrate a potential beneficial effect by combining fractionated Taxol exposure with fractionated irradiation without evidence for G2/M arrest in DNA analysis.

Animals↗