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R Sauer

Publications and source records attributed to R Sauer.

At least 37 records · Page 2Linked to original sources
PubMed1998

Eight-year results of a prospective non-randomised study on therapy of small breast cancer. The German Breast Cancer Study Group (GBSG).

In this report, the results of the first controlled clinical trial on breast cancer in Germany, begun in 1983, are presented after a median follow-up of 8 years. Four-year results have been previously published. In pT1 N0 M0 breast cancer, mastectomy as the standard treatment was to be compared with tumorectomy plus radiotherapy to the remaining breast tissue. The study design, originally planned as a comprehensive cohort study including randomised and non-randomised patients, had to be changed into a prospective observation study due to the low randomisation rate. 1036 out of 1119 recruited patients were evaluable. After a median follow-up of 97 months, 237 events (local recurrence, regional recurrence, distant metastases, contralateral breast cancer or death of the patient without previous recurrence) occurred. With the exception of death without recurrence, the events were evenly distributed among the two treatment groups. The 8-year local recurrence rate of the whole patient population is 8.8%. Out of all prognostic factors examined, only tumour size and grade had a significant influence on recurrent disease. Event-free survival decreased in cases with 'uncertain' tumour margins, whereas the width of the margin has no influence on disease recurrence. Based on 151 deaths observed so far, there was no significant difference in overall survival between the two treatment groups. The 8-year results of this study are in accordance with the 4-year results reported previously and with those of other breast-conserving treatment trials. There was no significant difference between the two treatment groups with regard to event-free and overall survival. Incomplete tumorectomy had a negative influence on recurrence.

Adult↗
PubMed1998

Estimation of DNA single-strand breaks by single cells gel electrophoresis in tumor cells.

To estimate the frequency of single-strand breaks on a single cell level the so-called comet-assay (single cell gel electrophoresis) is a well-established technique. We present a modified protocol suitable for testing primary tumors, a kind of tissue very uneasy to be analysed in former single cell gel electrophoresis assays. Tumor cells of 12 studied cases showed a typical dose-rate effect on in vitro irradiation with different X-ray doses, as observed in peripheral blood leukocytes. Interestingly, the repair capability of primary tumor cells was lower than that of peripheral blood leukocytes of the same patients.

Adenocarcinoma↗
PubMed1998

Management of carcinoma of the bladder.

Carcinoma of the bladder (CaB) is a common tumor of the genitourinary tract. In the United States in 1997, CaB was second in frequency of occurrence and third in mortality among genitourinary tumors. This tumor has a well-documented history of environmental and industrial causative factors. The strongest etiologic risk factors include the use of tobacco, which is thought to be responsible for half of the CaB diagnosed in men in the United States, and some arylamines. In the past 30 years, there has been major improvement in the survival of patients with this disease. Multiple factors were responsible for this accomplishment and they include: 1) better understanding of the natural history of CaB, 2) development of immunohistochemical analysis helpful in defining prognostic factors, 3) improved imaging and nonimaging diagnostic modalities helpful in making earlier diagnosis and better defining the true anatomical extent of the tumor, 4) development of more effective therapy for carcinoma in situ, 5) major improvement in surgical techniques resulting in better treatment outcomes, and 6) the wide use of adjuvant chemotherapy. Major stress has been placed on the quality of life of patients treated for CaB. Quality of life was improved by optimizing surgical, radiation, and medical treatment techniques. The two most important factors producing this quality-of-life improvement include: 1) the use of organ-preserving therapy in properly selected patients that involves the use of a multimodality therapeutic approach with transurethral resection, radiation therapy, and chemotherapy; and 2) the ability to treat selected men and women with radical cystectomy followed by orthotopic reconstruction that allows patients nearly physiologic voiding. Current research efforts are directed toward better patient selection for appropriate therapy which is expected to increase patient survival and improve quality of life. Of particular importance in the selection of this optimal therapy in patients with CaB is a wide application in the clinical practice of important recent advances in molecular genetics.

Carcinoma↗
PubMed1998

Replacement of dietary saturated by unsaturated fatty acids: effects of platelet protein kinase C activity, urinary content of 2,3-dinor-TXB2 and in vitro platelet aggregation in healthy man.

The present study was conducted to compare the effects of oleic (OA) and linoleic acids (LA) on platelet function in healthy subjects. After a 4-week period on a diet rich in saturated fatty acids (SAFA), 38 volunteers (20 female, 18 male) had a high OA (18.0 en%) diet or a high LA diet (11.5 en%) for four weeks in a controlled manner. A control group of 13 subjects consumed their habitual diet throughout the study. Replacing the SAFA diet by the OA or LA diet did not affect the membrane-associated activity of platelet protein kinase C (PKC). However, both diets tended to increase the cytosolic activity to a comparable extent. Both the OA and the LA diets increased urinary excretion of 2.3-dinor-TXB2, as compared to the SAFA diet, whereas the urinary excretion of beta-thromboglobulin remained unchanged. As compared to the initial SAFA diet, platelet aggregation to collagen increased after both diets, while ADP induced aggregation showed no diet-induced changes. The results indicate increased platelet activity after both oil diets with no differences between the OA and LA diet and confirm in vitro findings that cis-unsaturated fatty acids have a distinct effect on cytosolic PKC, in particular.

Adult↗
PubMed1997

Prevention of heterotopic ossification about the hip: final results of two randomized trials in 410 patients using either preoperative or postoperative radiation therapy.

PURPOSE: Experimental and clinical data support effectiveness of perioperative radiotherapy to prevent heterotopic ossification after hip surgery or trauma. Since 1987, two prospectively randomized trials were performed in patients with high-risk factors to develop heterotopic ossification: the first (HOP 1) to assess the prophylactic efficacy of postoperative low vs. medium dose radiotherapy, and the second (HOP 2) to assess the prophylactic efficacy of pre vs. postoperative radiotherapy. METHODS AND MATERIAL: 410 patients with high risk to develop heterotopic ossifications about the hip following hip surgery were recruited. Between June 1987 and June 1992, 249 patients were randomized in HOP 1 to postoperative "low dose" (5 x 2 Gy; total: 10 Gy) or "medium dose" (5 x 3.5 Gy; total: 17.5 Gy) radiotherapy. Between July 1992 and December 1995, 161 patients were randomized in HOP 2 to either 1 x 7 Gy preoperatively (< or = 4 h before surgery) or 5 x 3.5 Gy (total: 17.5 Gy) postoperatively (< or = 96 h after surgery). With exception of age and type of implant (cemented vs. uncemented prosthesis) all confounding patient variables (gender, prior surgery) and predisposing risk factors were similarly distributed between both trials and treatment arms. Portals encompassed the periacetabular and intertrochanteric soft tissues. Radiographs were obtained prior and immediately after surgery and at least 6 months after surgery to assess the extent of ectopic bone formation about the hip. Modified Brooker grading was used to score the extent of heterotopic ossification. Harris scoring was applied to evaluate the functional hip status. If the scores decreased from immediate post or preoperative status, respectively, to the last follow-up, radiological or functional failures were assumed. RESULTS: Effective prophylaxis was achieved in 227 (91%) hips of HOP 1 and in 142 (88%) of HOP 2. In HOP 1, 15 (11%) radiological failures were observed in the low-dose group compared to 7 (6%) in the medium dose group (p > 0.05). In HOP 2, 4 (5%) radiological failures were observed in the postoperative and 11 (19%) in the preoperative group (p < 0.05). Subgroup analysis of the preoperative group revealed that the highest failure rate occurred in patients with prophylactic radiotherapy prior to removal of ipsilateral Brooker Grade III and IV ossification (39%) (p < 0.001), while all other patients in the preoperative group had a failure rate that was comparable to postoperative treatment groups. In multivariate logistic regression analysis the number of high-risk factors for development of heterotopic ossification (p = 0.03) and the time to RT initiation (p = 0.05) were independent prognostic factors in the HOP 1 study. For the HOP 2 study, the multivariate logistic regression analysis revealed the number of high-risk factors for development of heterotopic ossification (p = 0.003), the preoperative HO grade (p = 0.001) and the RT dose concept (p = 0.05) as independent prognostic factors. Other factors including type of implant (cemented vs. uncemented) did not affect the prophylactic efficacy of radiotherapy. There were no increased intra- and postoperative complications seen in the preoperative group, and no long-term complications were observed in both HOP studies. For functional failures (decrease of Harris score) no statistically prognostic factors were found. There were less functional failures in HOP 1 (18 = 7%) than in HOP 2 (23 = 14%, but this difference was not statistically significant. Only patients with high Brooker Grade III and IV at last FU achieved a lower Harris score than those with low Brooker Grade 0, I and II (p < 0.05). CONCLUSION: With the exception of a small subgroup of patients with ipsilateral high Brooker Grade III and IV, pre- and postoperative radiotherapy are equally effective to prevent heterotopic ossification about the hip after hip surgery and total hip arthroplasty. Fractionated medium dose radiotherapy resulted in the low

Adult↗
PubMed1997

Aza-analogs of 8-styrylxanthines as A2A-adenosine receptor antagonists.

In the present study we synthesized aza-analogs of 8-styrylxanthines, in which the ethenyl bridge is replaced by an imine, amide, or azo function, in order to investigate structure-activity relationships of the 8-substituent of A2A-selective xanthine derivatives. Thus, various 8-substituents were combined with theophylline or caffeine, respectively, and affinities of the novel compounds for adenosine A1- and A2a-receptors were determined and compared with those of analogous 8-styrylxanthine derivatives. 8-(Benzylideneamino)caffeine derivatives exhibited high affinity and selectivity for A2A-adenosine receptors, but were unstable in aqueous buffer solution at physiological pH values. 8-(Phenylazo)caffeine derivatives were less potent than corresponding 8-styrylcaffeine derivatives at adenosine receptors. The most potent azo compound of the present series was 8-(m-chlorophenylazo)caffeine (14b) exhibiting a Ki value of 400 nM at A2A-adenosine receptors and 20-fold selectivity versus A1-receptors. Due to the facile synthetic access to 8-(phenylazo)xanthine derivatives, which are obtained by coupling of 8-unsubstituted xanthines with phenyldiazonium salts, 14b may be an interesting new lead compound for the development of more potent and selective A2A-antagonists with azo structure.

Adenosine↗
PubMed1997

[Therapy pf cervical lymph node metastases of unknown primary tumor].

BACKGROUND: The primary tumor remains unknown in approximately 3 to 9% of patients with lymph node metastases in the neck. Management of these patients is still controversial particularly because of the commonly as poor assessed prognosis. The treatment outcome was surveyed by a retrospective analysis, trying to identify prognostic factors. PATIENTS AND METHODS: From 1979 through 1993, 64 patients with metastatic carcinoma of unknown primary tumor involving neck lymph nodes were treated. Most of them (n = 40) were squamous cell carcinomas. Forty-eight patients underwent surgical resection of the involved nodes by neck dissection or excisional biopsy. Surgery was performed in 41 patients before and in 7 patients after radiotherapy. Additional chemotherapy was administered to 12 patients (simultaneously to 11 patients). The irradiated volume included both sides of the neck, the supraclavicular region and the whole pharynx. The mean radiation dose was 59 Gy. In 32 patients, an additional boost to epipharynx (n = 23) and/or large lymph nodes (n = 11) was given (mean: 12 Gy) by external beam therapy, in 2 cases by interstitial implants (22 Gy). Mean follow-up time was 8 years (range: 7 months to 15 years, median: 9 years). RESULTS: Fifty-two out of 64 (81.2%) patients came into a complete remission and 12 into a partial remission. The cause specific survival after 5 years for the whole group was 51.0 +/- 7%, the overall survival 38.8 +/- 7%. Within the irradiated area the tumor control was 68.3 +/- 7%, the distant metastatic-free survival 70.0 +/- 7%. Best results showed patients after surgery+radiation (n = 48) with 67% overall survival at 5 years versus 0% (median: 9.2 months) without surgery (n = 16), and patients with lymph nodes located above the glottic level (n = 49) 63.2% versus 9.0% (median: 1.2 years, n = 12). The primary tumor appeared in 9 patients (4 times above the clavicles), once in the irradiated volume. CONCLUSION: Patients with cervical metastases of unknown primaries do not fare worse than patients with advanced carcinoma of head and neck and should be treated with a curative intent preferably by surgery and radiotherapy.

Adult↗
PubMed1997

[The acute toxicity of the simultaneous radiochemotherapy of rectal carcinoma].

AIM: We retrospectively examined the acute toxicity of (neo-)adjuvant combined treatment for rectal cancer in an attempt to evaluate potential factors that influence the severity of toxic side effects. PATIENTS AND METHOD: Between 1987 and 1995, 120 patients with rectal cancer (73 patients with primary tumor, 47 with recurrent disease) received chemoradiation for rectal cancer. Fifty-six patients received preoperative chemoradiation, 64 patients were treated postoperatively. Radiation was given by 4-field box technique with 6 to 10 MV-photons. Daily fraction size was 1.8 Gy, total dose 50.4 Gy (range: 41.4 to 56 Gy) +/- 5.4 Gy (range: 3.6 to 19.8 Gy) local boost in selected cases, specified to the ICRU reference point. During the first and fifth week of radiation 5-FU at a dose of 1000 m2/d for 120 hours was administered by continuous infusion. Toxicity was recorded following (modified) WHO-criteria. RESULTS: Acute grade 3 toxicity occurred mainly as diarrhea (33%), perineal skin reaction (37%), and leukopenia (10%). Extension of the treatment volume including paraaortic lymph nodes (L3) led to a significant increase of grade 3-diarrhea (68% vs. 25%, p = 0.0003) and grade 3-leukopenia (18% vs. 8%, p = 0.03). After abdominoperineal resection less patients suffered from grade 3-diarrhea (8% vs. 47% after sphincter preserving procedures, p = 0.0006), whereas severe perineal erythema occurred more frequently (56% vs. 29%, p = 0.02). Women had significantly more toxic side effects (grade 3-diarrhea: 39% vs. 16% in men, p = 0.04; grade 2 to 3-nausea/emesis: 21% vs. 8% in men, p = 0.018; grade 2 to 3-leukopenia 53% vs. 31% in men, p = 0.02). After preoperative chemoradiation a significant reduction of grade 3-diarrhea (11% vs 29%, p = 0.03) and grade 3-erythema (16% vs. 41%, p = 0.04) was noted. CONCLUSION: Treatment volume, type of surgery, sex and sequence of treatment modalities are the most important factors that influence the severity of toxic side effects. Individual adjustment of 5-FU dosage by monitoring its systemic clearance (which is lower in women) could help to avoid toxic side effects. The reduced acute toxicity of the preoperative approach provides a further argument in favor of the neoadjuvant chemoradiation for rectal cancer.

Acute Disease↗
PubMed1997

[G-CSF in radiochemotherapy].

BACKGROUND: G-CSF enhances the division, maturation and release of granulocyte precursor cells. The shortening of chemotherapy-induced leukopenia via G-CSF is well documented in literature, with fractionated radiotherapy alone one finds a distinct increase of the granulocyte level. There are only few results for combined simultaneous radiochemotherapy. PATIENTS AND METHODS: In the Department of Radiotherapy of the University of Erlangen 102 patients were treated with G-CSF since 1992. Twenty-eight patients (31 applications) undergoing radiotherapy only (n = 4) or combined simultaneous radiochemotherapy (n = 27) received G-CSF interventional daily. These results are presented and discussed. Indications for the application of G-CSF were severe leukopenia below 1000/mm3 (level IV according to WHO) or rapid decreasing leukocytes during therapy. G-CSF was not applied during chemotherapy and terminated at least 24 h before the next chemotherapy cycle. r-metHuG-CSF (Filgrastim, Neupogen) was used subcutaneously. Documented were the duration until the leukocyte increase, neutrophil granulocytes, thrombocytes, interruption of radiotherapy, febrile episodes and side effects. RESULTS: In case of severe leukopenia (< 1000/mm3 n = 16) the leukocytes increased after 3 days of G-CSF application, the radiotherapy was interrupted in 2 cases, terminated in 1 case. Four patients had lever before during G-CSF 4 additional febrile episodes occurred. If G-CSF application was started between leukocyte levels of 1000 and 1500/mm3 after 1 day the leukocytes increased in 9 of 10 cases beyond the starting level. Interruption of radiotherapy was not necessary. Only 1 febrile episode occurred (1/11). There were no relevant side effects of G-CSF. CONCLUSIONS: Rapidly developing or severe leukopenia during radio(chemo)therapy are indications for an interventional application of G-CSF. The leukocyte level for the start of G-CSF should be chosen so that without G-CSF an interruption of therapy or a level IV leukopenia seems to be unavoidable.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Radiotherapy in the early stage of Dupuytren's disease. The indications, technic and long-term results].

AIM: Radiotherapy was applied in our clinic to prevent the disease progression in early stage Dupuytren's contracture. Initial response, long-term outcome, acute and late toxicity of the treatment were evaluated in a retrospective analysis. PATIENTS AND METHOD: Between 1982 and 1993, 96 patients (142 hands) received orthovoltage radiotherapy, which consisted of 2 radiotherapy courses with daily fractionation of 5 x 3 Gy (total dose: 30 Gy) separated by a 6 weeks interval. The Dupuytren's contracture was staged according to the classification of Tubiana et al. [38]. The initial evaluation was performed 3 months after completion of radiotherapy, while long-term outcome was analysed at last follow-up between February and April 1994. The mean follow-up was 6 +/- 2 (range 1 to 12) years. Fifty-seven patients with a follow-up of > or = 5 (median 7,5; mean 9,5 to 12) years were separately evaluated for long-term outcome, i.e. prevention of disease progression. Acute and late treatment toxicity was assessed using the RTOG/EORTC criteria. RESULTS: According to stage, 130 (92%) cases remained stable at 3 months follow-up, 10(7%) improved and 2 (1%) progressed. An objective reduction of symptomatic cords and nodules was achieved in 107 (75%) cases at 3 months follow-up. Moreover, 87% of the patients reported a subjective relief of symptoms. In long-term follow-up, only 16 of 142 (11%) cases had progressed according to stage. In the group with a minimum follow-up of 5 years (n = 57), 44 (77%) patients experienced no progression, while 13 (23%) progressed inside (8 cases) or outside (5 cases) of the radiotherapy field. Many "failures" could have been avoided with appropriate choice of larger safety margins included in the treated portals, however, most failures were successfully managed by a second radiotherapy or hand surgery. CONCLUSION: Radiotherapy prevents disease progression for early stage Dupuytren's contracture. Thus, an otherwise necessary surgical procedure in advanced stages of Dupuytren's contracture can be avoided. Moreover, in case of disease progression despite radiotherapy a second radiotherapy or salvage operation is still feasible.

Adult↗
PubMed1997

[Topoisomerase I inhibitor with potential radiosensitizing effect].

AIM: In search of new drugs which should be theoretically able to modify radiation effects, the topoisomerase I-inhibitor topotecan was identified in November 1996, approval for second-line therapy of ovarian carcinoma was given in Germany. MATERIAL AND METHOD: This review article describes mechanisms of action, pharmacokinetic, preclinical and recent clinical data on topotecan with and without concomitant radiation therapy. RESULTS: Following a 30 min. intravenous bolus, median plasma half-lives between 2 and 3 h. and a total-body clearance of 0.57 l/min/m2 were seen. After oral administration the bioavailability varied between 30 and 35%. Topotecan is able to pass the blood brain barrier. Encouraging clinical results are reported in gastrointestinal tumors, head and neck squamous cell carcinoma, small cell and non-small cell lung cancer, breast cancer, leukemia and pediatric tumors in addition to ovarian carcinoma. Recent studies indicate that topotecan functions as a radiosensitizer and may be applied together with radiation in future trials. In vivo and in vitro experiments revealed a good modulation ofradiation effects of topotecan. CONCLUSIONS: In experimental and preclinical studies using topotecan both additive and sensitization effects to normal cells and tumor cells were seen by ionizing radiation. Clinical phase II/III trials may preferentially be indicated in non-small cell lung cancer and primary and metastatic brain tumors.

Antineoplastic Agents↗
PubMed1997

[Regression of Yoshida sarcoma during normoxia and hypoxia after fractionated irradiation].

PURPOSE: Tumor regression is one of the most important factors determinating the tumor control probability after radiotherapy. The changes in the regression of tumors during fractionated radiotherapy and the application of different radioprotectors or radiosensitizers make render to assess their effectivity. MATERIAL AND METHOD: The effect of hypoxic breathing (8.1% O2) on the tumor regression of Yoshida sarcoma was studied using rats of Wistar strain. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy. RESULTS: No significant changes in the tumor regression after radiotherapy in any group in any time independent from respiratoric hypoxia were recorded. The tumor regression rate was significantly influenced by treatment schedule (p < 0.0005). CONCLUSIONS: Our results support the hypothesis of hypoxy-radiotherapy: The acute hypoxic hypoxia, caused due the breathing of hypoxic gas mixture with 8 to 10% oxygen, did not influence the radiation induced tumor regression in animal experiment. For this criterium no protection can be shown. The influence of hypoxy-radiotherapy on the local tumor control is necessary to evaluate in further experiments.

Acute Disease↗
PubMed1997

[Epicondylopathia humeri. The indication for, technic and clinical results of radiotherapy].

BACKGROUND: The efficacy of radiotherapy for degenerative-inflammatory disorders is well known, but so far long-term observations and reliable assessment of symptoms according to objective criteria and scores for validation are still missing. PATIENTS AND METHOD: From 1986 to 1991, 104 patients with refractory epicondylopathia humeri were irradiated. 85 patients or 93 elbows (due to double-sided symptoms) were documented in long-term follow-up according to objective criteria. All patients had received intensive therapy. Pain symptoms were quantified in "categories" and "grades" prior to and 6 weeks after radiotherapy and at last follow-up. In addition, the elbow score of Morrey et al. [36] was used for long-term evaluation. The onset of pain symptoms was acute in 41 and chronic in 52 cases. The mean symptom duration prior to radiotherapy was 16 months. Pain was mostly triggered off during professional (46) or sportive activities (23) or spontaneously (11). Fifty-one patients were severely disabled in professional or sportive activities. The involved elbow(s) received 2 radiotherapy series of 6 x 1 Gy (total 12 Gy) with 3 fractions per week; the second radiotherapy series was started 6 weeks after the first series. Mean follow-up was 4 +/- 2 (1 to 8) years. RESULTS: Forty-three patients (50 elbows) achieved "complete pain relief (CR)" in all pain categories: 59% elbows with pain at strain had "complete pain relief", 79% with pain at night, 84% with permanent pain, 80% with pain at rest and 81% with pain at initiation or morning stiffness. Nineteen elbows gained "major pain relief (PR)", i.e. had minor symptoms (maximum grade 1) in all categories. Thus, a total of 69 (74%) elbows responded to radiotherapy. Seventeen patients (19 elbows) were operated because of persistent symptoms or dissatisfaction in long-term follow-up; 7 of those became completely free of symptoms. The Morrey-Score improved by a mean of 18 points from 78 prior to radiotherapy to 96 points at last follow-up. According to the Morrey-Score only 2 patients became worse in long-term follow-up. Two parameters indicated a negative prognosis in multivariate analysis: long symptom duration prior to radiotherapy and immobilisation with plaster (p < 0.05). CONCLUSIONS: Radiotherapy for refractory epicondylopathia humeri is highly effective. Long symptom duration and long-term immobilisation by plaster are negative prognostic factors for treatment outcome. Due to the low side effects and treatment costs, radiotherapy is a good therapeutic option in comparison to conventional treatment methods and surgery in the chronic stage of epicondylopathia humeri.

Acute Disease↗
PubMed1997

[Oxygen pressure distribution in lymph node metastases and the changes during acute respiratory hypoxia].

PURPOSE: The radiosensitivity of tissues is essentially influenced by hypoxia. Based on the oxygen effect a new therapeutic modality has been developed to protect healthy tissues while hypoxic breathing during irradiation. PATIENTS AND METHOD: The effect of hypoxic breathing (8.1% O2) on the pO2 in metastatic lymph nodes was studied in 14 patients. Tissue oxygenation was assessed using a polarographic electrode system. RESULTS: The median pO2 was 19.6 mm Hg prior to hypoxic breathing with a great intra- and intertumoral variability. The relative frequency of pO2-values < 5 mm Hg was between 0 and 88%. During hypoxic breathing we registered no significant changes in the mean, the median or the pO2 values < 5 mm Hg. CONCLUSIONS: In metastatic lymph nodes can be found chronic hypoxia with great inter- and intratumoral pO2 variability. The hypoxic breathing (8.1% O2) shows no significant modifications of the tumor oxygenation with increased pO2 variability. This fact explains the experimental and clinical experience, that the hypoxic breathing (8 to 10% O2) protects the healthy tissue without changes in the radiosensitivity of chronic hypoxic tumor tissue.

Acute Disease↗