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Jürgen Dunst

Publications and source records attributed to Jürgen Dunst.

At least 19 recordsLinked to original sources
PubMed2006

Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1alpha-related markers, and hemoglobin levels.

PURPOSE: The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma marker of tumor hypoxia. However, the association of immunohistochemical OPN expression in tumor sections with tumor oxygenation parameters (HF5, median pO(2)), the hypoxia-related markers hypoxia-inducible factor-1alpha (HIF-1alpha) and carbonic anhydrase IX (CAIX), or hemoglobin and systemic vascular endothelial growth factor (VEGF) levels has not been investigated. METHODS AND MATERIALS: Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radiotherapy were assessed by immunochemistry for the expression of OPN, HIF-1alpha, and CA IX. Relationship of OPN expression with tumor oxygenation parameters (HF5, median pO(2)), HIF-1alpha and CA IX expression, hemoglobin and serum VEGF level, and clinical parameters was studied. RESULTS: Bivariate analysis showed a significant correlation of positive OPN staining with low hemoglobin level (p = 0.02), high HIF-1alpha expression (p = 0.02), and high serum vascular endothelial growth factor level (p = 0.02) for advanced head-and-neck cancer. Furthermore, considering the 31 Stage IV patients, the median pO(2) correlated significantly with the OPN expression (p = 0.02). OPN expression alone had only a small impact on prognosis. However, in a univariate Cox proportional hazard regression model, the expression of either OPN or HIF-1alpha or CA IX was associated with a 4.1-fold increased risk of death (p = 0.02) compared with negativity of all three markers. CONCLUSION: Osteopontin expression detected immunohistochemically is associated with oxygenation parameters in advanced head-and-neck cancer. When the results of OPN, HIF-1alpha, and CA IX immunohistochemistry are combined into a hypoxic profile, a strong and statistically significant impact on overall survival is found.

Adult↗
PubMed2006

Survivin protein expression and hypoxia in advanced cervical carcinoma of patients treated by radiotherapy.

BACKGROUND: Survivin is strongly overexpressed in the vast majority of cancers. Initial investigations suggest a role for Survivin in radiation resistance. In this study, we investigate the effect of Survivin expression on clinical outcome and its relationship to tumor oxygenation parameters, expression of Hif-1alpha and anemia in patients with advanced cervical cancers treated with radiotherapy. MATERIAL AND METHODS: Biopsies of 44 patients with cervical cancers (Stage IIB: n=9; Stage IIIB: n=31; Stage IVA: n=4) treated with radiotherapy were assessed by immunochemistry for expression of Survivin. Relation of Survivin to pretreatment tumor oxygenation parameters (HF5, pO(2)), hemoglobin (hb) level, Hif-1alpha expression and clinical parameters were investigated. RESULTS: Survivin expression was detected in all tumors of the 44 patients. Seven showed a strong expression and 37 have moderate Survivin expression. Patients whose tumors showed moderate Survivin expression had a 5-year overall survival of 66%. However, only one of the seven patients with strong Survivin expression was alive 45 months after treatment. In a Cox regression analysis, Survivin expression was correlated to poor overall survival (p=0.02, RR=3.3). There was no relationship between Survivin expression and pO(2) or HF5, but rather an inverse correlation with hemoglobin level (p=0.04). Furthermore, for six of the seven tumors with a high Survivin expression, Hif-1alpha was detected. CONCLUSION: Survivin protein expression is linked with anemia and prognosis in advanced cervical carcinoma of patients treated by radiotherapy.

Adult↗
PubMed2006

Plasma osteopontin levels in patients with head and neck cancer and cervix cancer are critically dependent on the choice of ELISA system.

BACKGROUND: The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma surrogate marker of tumor hypoxia and as an indicator of the presence of pleural mesothelioma in asbestos-exposed individuals. The clinical introduction of plasma OPN measurements requires the availability of a reliable enzyme-linked immunosorbence assay (ELISA). METHODS: We compared previously described and currently available ELISA systems on 88 archival plasma samples obtained from patients with head and neck or cervix cancer between 20 days before and 171 after the start of radiotherapy. RESULTS: Median (range) plasma OPN levels were 667 (148.8-2095) ng/ml and 9.8 (3.5-189.5) ng/ml for a previously described and a newly marketed assay, respectively. Although results for different assays were significantly correlated (r = 0.38, p < 0.05, Spearman rank test), between-assay factors ranged from 2.0 to 217.9 (median 74.6) in individual patients. OPN levels in cervix cancer patients were comparable to those of head and neck cancer patients. CONCLUSION: Commercially available OPN ELISA systems produce different absolute plasma OPN levels, compromising a comparison of individual patient data with published results. However, different assays appear to have a similar capacity to rank patients according to plasma OPN level. A review of literature data suggests that plasma OPN levels measured even with identical ELISA systems can only be compared with caution.

Enzyme-Linked Immunosorbent Assay↗
PubMed2006

Radiochemotherapy after transurethral resection for high-risk T1 bladder cancer: an alternative to intravesical therapy or early cystectomy?

PURPOSE: For high-risk T1 bladder cancer, the most important issue is how to restrict radical cystectomy to selective patients with a high likelihood of tumor progression and to choose an initial bladder-sparing approach in others without affecting survival. Radiotherapy or radiochemotherapy (RT/RCT) may help to strike a balance between intravesical treatment and early cystectomy. PATIENTS AND METHODS: Between 1982 and 2004, 141 patients with high-risk T1 bladder cancer (84 patients with T1 grade 3 [T1G3]; others with T1G1/2 and associated carcinoma-in-situ, multifocality, tumor diameter > 5 cm, or multiple recurrences) were treated with RT (n = 28) or platinum-based RCT (n = 113) after transurethral resection of bladder tumor (TURBT). Six weeks after RT/RCT, response was evaluated by restaging TURBT. Salvage cystectomy was recommended for patients with persistent disease and for tumor progression after initial complete response (CR). Median follow-up was 62 months; 65 patients have been observed for 5 years or more. RESULTS: CR was achieved in 121 of 137 patients (88%; four patients without restaging TURBT). Tumor progression for the entire group of 141 patients was 19% and 30% at 5 and 10 years, respectively (for 121 patients with CR, 15% and 29%; for 84 patients with T1G3, 13% and 29%, respectively). Disease-specific survival rates were 82% and 73% at 5 and 10 years (CR, 89% and 79%; T1G3, 80% and 71%, respectively). More than 80% of survivors preserved their bladder; 70.4% were "delighted" or "pleased" with their urinary function. CONCLUSION: RT/RCT after TURBT with selective bladder preservation is a reasonable alternative to intravesical treatment or early cystectomy for high-risk T1 bladder cancer.

Administration, Intravesical↗
PubMed2006

[Role of radiation therapy on the use of primary ("neoadjuvant") systemic treatment of breast cancer].

BACKGROUND: The indications for primary ("neoadjuvant") systemic treatment (PST) for breast cancer have evolved over the last few years. PST is not only used in patients with locally advanced breast cancer (LABC) and inoperable tumors but also plays a role for operable tumors aiming at breast conservation and higher complete remission rates (ypCR). The contribution of radiotherapy and the optimal sequencing of chemotherapy, surgery and radiotherapy still have to be defined. MATERIAL AND METHODS: Objectives and results of PST for inflammatory, locally advanced and operable breast cancer were analyzed according to tumor stage. RESULTS: Radiotherapy following PST and surgery is the standard of care for inflammatory breast cancer, LABC and nonresectable lesions. Comparable results are achieved for good responders after PST receiving radiotherapy or surgery. The evaluation of a preoperative radiotherapeutic approach is complicated by different chemo- and radiotherapy regimens, continuation of chemotherapy after surgery and heterogeneous patient groups. CONCLUSION: For LABC and inflammatory breast cancer the role of PST is well defined. For operable lesions, however, the value of preoperative radiotherapy still has to be established. This should be assessed within the framework of a clinical trial using standardized parameters for applying chemotherapy as well as radiation therapy.

Adult↗
PubMed2005

Radiotherapy in Ewing tumors of the vertebrae: treatment results and local relapse analysis of the CESS 81/86 and EICESS 92 trials.

PURPOSE: Treatment results in patients with Ewing tumors of the vertebrae enrolled in the Cooperative Ewing's Sarcoma Study (CESS) 81, 86, and the European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) 92 trials were analyzed with special emphasis on radiation-associated factors. PATIENTS AND METHODS: A retrospective analysis was performed on 116 patients with primary tumors of the cervical, thoracic, or lumbar vertebrae treated between 1981 and 1999. Furthermore, a relapse analysis was done on those patients who underwent radiotherapy and subsequently had a local recurrence. RESULTS: A total of 64.6% of the patients received definitive radiotherapy; 27.5% of patients had surgery and radiotherapy. Only 4 patients (3.4%) underwent definitive surgery. Twenty-seven patients presented with metastases at diagnosis. 22.4% of the total group developed a local relapse. Among the subgroup with definitive radiotherapy, local recurrence was seen in 17 of 75 patients (22.6%). Event-free survival and survival at 5 years were 47% and 58%, respectively. Of the 14 evaluable patients with a local relapse after radiotherapy, 13 were in-field. No correlation between radiation dose and local control could be found. CONCLUSION: Surgery with wide resection margins is rarely possible. The results after definitive radiotherapy in vertebral tumors are comparable to those of other tumor sites when definitive radiotherapy is given. Nearly all local relapses after radiotherapy are in-field.

Adolescent↗
PubMed2005

Effects of recombinant human erythropoietin (rHuEPO) on tumor control in patients with cancer-induced anemia.

It is well recognized that anemia-induced tumor hypoxia is associated with a reduced sensitivity of tumors to radiation and some forms of chemotherapy. Thus, the correction of lower hemoglobin (Hb) concentrations with recombinant human erythropoietin (rHuEPO) can play an essential role by improving tumor oxygenation. Based on evidence from a number of trials, treatment with rHuEPO will effectively ameliorate anemia and improve quality of life. However, one of the most essential prerequisites for achieving this benefit is the use of rHuEPO in agreement with the evidence-based ASCO/ASH-guidelines recommending a target Hb concentration of 12 g/dl (7.44 mmol/l).

Anemia↗
PubMed2005

[Prognostic factors after surgery and adjuvant radiotherapy in cervical cancers. A retrospective analysis of 298 patients after surgery and adjuvant radiotherapy].

PURPOSE: To determine prognostic factors in patients with cervical cancer treated with surgery followed by radiotherapy. PATIENTS AND METHODS: In a retrospective analysis, patients treated at the Department of Radiotherapy, University of Halle-Wittenberg, Germany, from 1980 through 1993 were evaluated for local control, survival and treatment sequelae with special emphasis on prognostic factors. 298 patients (age 23-81 years, median 46 years) with cervical cancers were treated with surgery followed by radiotherapy to a minimum of 50 Gy. 250 patients received radiotherapy after radical hysterectomy with pelvic lymphadenectomy and 48 patients after hysterectomy. Most of the cancers were squamous cell carcinomas (81%) with few adenocarcinomas (12.4%). Grading was G1/G2 in 28.9% of the patients and G3/G4 in 39.6%. RESULTS: The 5-year overall survival was 68.8% for the whole group, 70.5% for squamous cell carcinomas (n = 241), 64.4% for adenocarcinomas (n = 37; not significant), 80% for G1/G2 tumors (n = 86), and 69% for G3/G4 carcinomas (n = 118; p = 0.074). Survival dependent on tumor size and positive nodes was 76.2% (n = 94) for pT1N0, 65.8% for pT1N+ (n = 31), 68.2% for pT2N0 (n = 62), and 41.4% for pT2N+ (n = 35). An impact of grading on 5-year survival was only found in patients with positive nodes: G1/G2N0 84% (n = 62) versus G1/G2N+ 64.8% (n = 23); G3/G4N0 79.6% (n = 71) versus G3/G4N+ 39.9% (n = 31). The number of positive nodes was the strongest prognostic factor. Multivariate analysis (Cox regression) established a risk factor of 3.06 (p < 0.01) for positive nodes, of 1.7 for grading G1/G2 versus G3/G4 (p = 0.087), and of 1.3 for tumor size (pT1 vs. pT2; p = 0.079). There were no differences in the clinical outcome between patients in stage pT1 with or without lymphadenectomy (75% [n = 130] vs. 79% [n = 39]). CONCLUSION: In patients with cervical cancers treated with surgery and radiotherapy, positive nodes were an independent prognostic factor for local control and survival and should be an indication for additional chemotherapy. A value of lymphadenectomy for survival in this group of irradiated patients could not be established.

Adult↗
PubMed2005

[Quantitative and qualitative investigations of salivary gland function in dependence on irradiation dose and volume for reduction of xerostomia in patients with head-and-neck cancer].

BACKGROUND AND PURPOSE: Radiation treatment of head-and-neck tumors mostly leads to a damage to the salivary glands and a consequential permanent loss of saliva. The aim of this investigation was to establish a modern three-dimensional conformal radiotherapy (3D-CRT) to show a decrease in severe xerostomia in contrast to the proven conventional technique (K-RT) with photons and electrons. PATIENTS AND METHODS: Between April 2002 and September 2003, 32 patients (25 male, seven female, mean age: 58 years) with malignant tumors of the head and neck were included-after surgery or in case of inoperability with curative intent-in a prospective, nonrandomized study. 10/32 patients (31%) received K-RT with photons and electrons, and 22/32 patients (69%) 3D-CRT (six to eight photon portals). The quantity of saliva was measured as stimulated saliva flow rate (ml/5 min) prior to treatment, at the end, and 1, 6, and 12 months after termination of treatment. To find out the resulting mean dose of both parotid glands for every patient in Gray (D(mean) doses), the D(mean) doses of the ipsilateral and the contralateral parotid gland, determined by dose-volume histograms (DVHs), were averaged over. For calculation of the NTCP (normal tissue complication probability), the logistic model was used. RESULTS: In the trend the stimulated salivary flow rates were higher in the group with 3D-CRT than in the group with K-RT during the whole observation period (at 10 weeks after the start of radiotherapy 3D-CRT vs. K-RT with 1.56 +/- 1.6 vs. 0.82 +/- 1.2 ml/5 min; p < 0.1). The patients treated with the K-RT had, on average, significantly higher averaged D(mean) values than those irradiated with 3D-CRT (p < 0.012). Patients, who were irradiated with 3D-CRT for tumors of the larynx or hypopharynx, showed, on average, significantly lower D(mean) values than patients, who were treated with 3D-DRT because of oral cavity or oropharynx carcinomas or with K-RT irrespective of the primary tumor site (p < 0,003). The resulting dose for 50% complication probability (TD(50)) of the salivary glands was 36.9 Gy (30.9-43.5 Gy; 95% confidence interval). The gradient k of the curve located in point TD(50) was 7.7 (4.8-15.8; 95% confidence interval). CONCLUSION: Basically, 3D-CRT seems to be suitable as a standard for all patients with carcinomas of the oral cavity, oro- and hypopharynx. Especially in patients with tumors located in the larynx and hypopharynx, averaged D(mean) doses of both parotids during irradiation can be reached, to conserve salivary flow rates, which are similar to baseline flow rates.

Adult↗
PubMed2005

Organ-sparing treatment in muscle-invasive bladder cancer.

BACKGROUND AND PURPOSE: Organ-sparing treatment of bladder cancer by a trimodality approach is feasible and effective. In this study, the results of a series of patients are reported, who were, in the majority, not suitable for major surgery. PATIENTS AND METHODS: In the period from June 1995 through December 2003, 68 patients (64 males, four females) with urothelial bladder cancer were treated with curative intent. The median age was 68 years (range 42-82 years). Clinical T-category was 32x T2, 20x T3, and 16x T4. Transurethral resection was performed in all cases, and a complete TUR-BT (transurethral resection of bladder tumor) was attempted, if possible. Radiotherapy was administered in conventional fractionation (five fractions of 1.8 Gy per week) up to 50.4 Gy to bladder, and regional nodes and the whole bladder received a boost up to 54-59.4 Gy. 34 patients received concurrent cisplatin-based chemotherapy (25 mg/m(2) on days 1-5 and 29-33), and patients with impaired renal function were either treated with irradiation alone (n = 7) or received paclitaxel as alternative to cisplatin in a phase II protocol or on an individual decision (n = 27). The median follow-up was 34 months (range 2-104 months). RESULTS: A histologically confirmed complete remission (CR) on restaging cystoscopy was observed in 40/46 patients (87%) who underwent restaging cystoscopy. CR rates were not significantly correlated to T-category (CR: 24/32 T2, 9/19 T3, and 9/16 T4 tumors) or clinical nodal status. Patients with non-radical resection and macroscopic residual tumor (R2 resection) achieved a CR in only 39% (12/31); this figure was significantly lower as compared to patients with radical R0 TUR-BT (CR: 15/16, 94%, p = 0.013) Furthermore, age and preexisting anemia had no impact on response. The overall survival of the whole group was 45% after 5 years, and survival according to clinical T-category was 62% for T2, 43% for T3, and 19% for T4 (p = 0.015). In eleven patients, local disease progression or relapse was observed. So far, only one salvage cystectomy has been performed, due to contraindications to surgery in the majority of patients. CONCLUSION: The data obtained in this study confirm the high efficacy of TUR and radiochemotherapy for locally advanced bladder cancer.

Adult↗
PubMed2005

Cancer-related anemia: biological findings, clinical implications and impact on quality of life.

Anemia is a common symptom in cancer patients. The relationship among anemia, cancer progression and clinical outcomes of cancer treatment is complex and much remains to be elucidated. One hypothesis for an etiological link is that anemia contributes to the development of tumor hypoxia, which in turn has been shown to induce proteomic and genomic changes within the tumor cells that ultimately favor malignant progression and treatment resistance. A substantial body of clinical data indicates that anemia can be a significant independent prognostic factor for treatment response and survival in cancer patients treated with chemotherapy or radiotherapy. In addition, studies have shown a correlation between anemia and decline in quality of life (QOL) in cancer patients. Of the many factors that impact cancer patients' QOL, fatigue has emerged as the most prevalent, troubling, under-recognized and under-treated of all symptoms experienced by anemic cancer patients. Systematic correction of anemia with appropriate supportive therapies prior to or during chemotherapy or radiotherapy may enhance patients' QOL.

Anemia, Hypochromic↗
PubMed2005

Radiosensitization, after a combined treatment of survivin siRNA and irradiation, is correlated with the activation of caspases 3 and 7 in a wt-p53 sarcoma cell line, but not in a mt-p53 sarcoma cell line.

Survivin, a member of the inhibitor-of-apoptosis family is an essential protein for regular mitosis and is involved in an anti-apoptotic pathway. In some studies, an association between survivin expression and radiosensitivity has been described for tumor cells, but the relationship between p53 and survivin regarding radioresistance remains to be clarified. In order to increase the effect of irradiation on two sarcoma cell lines, A-204 with wt-p53 and US 8-93 with mt-p53, siRNA was applied to knock down survivin expression. The effects of combined treatment of siRNA treatment and irradiation were investigated by clonogenic survival assay, measurement of activity of caspases 3 and 7, Western blot hybridization for survivin and p53, and morphological analysis of apoptosis. Survivin knock down caused radiosensitization in the cell line A-204 (wt-p53) with an enhancement factor of 1.8 at 2 Gy (p=0.05) and 2.5 at 4 Gy (p=0.02), respectively. No radiosensitization was found in the cell line US 8-93 (mt-p53), when clonogenic survival was analyzed. These findings were supported by an increase in activity (up to 5.2-fold) of caspases 3 and 7 in cell line A-204 (wt-p53), but not in cell line US 8-93 (mt-p53) after a combined treatment of siRNA and irradiation. Our findings suggest that the wt-p53-caspase pathway is of importance for the radiosensitization induced by targeting survivin, which may have an impact on future gene therapeutical treatments.

Apoptosis↗
PubMed2004

Survival of patients in clinical stages I-IIIb of non-small-cell lung cancer treated with radiation therapy alone. Results of a population-based study in Southern Saxony-Anhalt.

BACKGROUND AND PURPOSE: Up to now, evidence about survival of patients with non-small-cell lung cancer treated with radiation therapy alone is only available from clinical studies. The authors analyzed survival experience depending on several prognostic factors from a population-based cancer registry and compared this to survival data from the literature. PATIENTS AND METHODS: Between April 1996 and September 1999, 1,696 patients with lung cancer were recruited by the Halle Lung Cancer (HALLUCA) Study. 1,183 patients were diagnosed as having non-small-cell lung cancer, and 188 in clinical stages I-IIIb (15.9%) were treated with radiation therapy alone. RESULTS: The median survival time of all patients was 10.2 months, the 2-year overall survival rate amounted to 15.8%. Besides tumor stage, radiation dose was found to be a statistically significant prognostic factor for survival in univariate analysis. The median survival time was 4.2 months for 66 patients treated with < 50 Gy, 10.7 months for 80 patients treated with 50 to < 60 Gy, and 18.9 months for 42 patients treated with >/= 60 Gy; the corresponding 2-year overall survival rates were 8.7%, 13.4%, und 35.2%. The significant influence of dose persisted even after adjustment for different confounders in a Cox regression model. CONCLUSION: Patients treated with 50 to < 60 Gy under a potentially curative therapeutic regimen had a significantly lower survival, compared to patients treated with >/= 60 Gy. In terms of quality assurance, the large proportion of patients treated with radiation doses below the curative range of >/= 60 Gy was unexpected.

Aged↗
PubMed2004

Radioprotective effects of amifostine in vitro and in vivo measured with the comet assay.

PURPOSE: The authors investigated whether a potential radioprotective effect of amifostine (WR-2721) after in vitro or in vivo administration can be detected with the comet assay. Moreover, it was determined whether radioprotection by WR-2721 is dependent on the concentration of amifostine or alkaline phosphatase (AP, the enzyme which activates the prodrug). Furthermore, the authors tried to detect possible interindividual differences in radioprotection by amifostine. MATERIAL AND METHODS: In vitro administration of amifostine: Freshly isolated lymphocytes from two healthy volunteers were incubated with different concentrations of AP (0-210 U/ml) and amifostine (0-5,000 microg/ml). IN VIVO ADMINISTRATION OF AMIFOSTINE: Blood samples were collected from six postoperative rectal cancer patients before and after intravenous administration of amifostine 500 mg (no pretreatment with radio- or chemotherapy). Leukocytes and lymphocytes were irradiated and repaired in vitro and investigated with the alkaline comet assay. The radioprotective effect was evaluated by calculating dose-modifying factors (DMFs) and the paired t-test. RESULTS: Amifostine alone did not alter the radiation-induced DNA damage in vitro. The addition of at least 0.5-1 U/ml AP was required. A significant radioprotective effect (p < 0.05) was seen after administration of amifostine in vitro for all concentrations investigated (250-5,000 microg/ml, initial DNA damage). A comparable radioprotective effect after in vivo administration of 500 mg amifostine was measured with a mean DMF of 0.87. Interindividual differences were present in vivo and in vitro. CONCLUSION: Amifostine 500 mg intravenously yields an adequate radioprotective concentration. The effect was only marginally improved by extreme concentrations of amifostine in in vitro experiments. The comet assay is capable of detecting small changes in radiosensitivity by amifostine.

Adult↗
PubMed2004

Management of anemia in patients undergoing curative radiotherapy. Erythropoietin, transfusions, or better nothing?

BACKGROUND AND RESULTS: Anemia is a well-known risk factor for decreased local control and survival in patients undergoing curative radiotherapy. There is clear evidence from recent clinical investigations that anemia is an independent risk factor and hemoglobin (Hb) levels during radiotherapy are important (and not pretreatment Hb levels). The most likely explanation for the prognostic impact is the association with tumor hypoxia. An "optimal" Hb range with regard to tumor oxygenation seems to exist, and Hb levels < 11 g/dl and > approximately 15 g/dl impair tumor oxygenation but have (over a broader range) no significant impact on normal tissue oxygenation. There is some evidence from retrospective and prospective studies that the response to radiotherapy and the prognosis, especially in cervical cancers, might be improved if the Hb levels during radiotherapy can be maintained in the optimal range, either by transfusions or by erythropoietin. The effect of any antianemic therapy should be analyzed according to whether or not treatment was successful with regard to achieving optimal Hb levels during irrradiation. Erythropoietin is probably more effective in steadily increasing and stabilizing Hb levels, but bears the risk of overcorrection of Hb levels. The clinical relevance of erythropoietin receptors on tumor cells remains questionable. CONCLUSIONS: Treatment of anemia with the objective of improving local control and survival in radiotherapy patients is probably more difficult and sophisticated than coping with symptoms of anemia or improving quality of life. Nevertheless, the potential of antianemic treatment is high on the basis of experimental and clinical data, and further clinical trials are warranted.

Anemia↗
PubMed2004

Radiosensitization of a human soft tissue sarcoma cell line US8-93 (mt-p53) with the oxidizer sodium peroxodisulfate.

Side effects make it necessary to seek new radiosensitizers with low systemic actions. Sodium peroxodisulfate is a strong oxidizer classified as a safe agent with low systemic effects. We have examined the effect of this oxidizer on the radiosensitivity of the radioresistant human soft tissue sarcoma cell line US8-93 (mt-p53). The effects of peroxodisulfate (0.02-3.0 mM) with or without irradiation were studied by clonogenic survival assay, comet assay and the induction of apoptosis. We found sodium peroxodisulfate to be nontoxic for US8-93 up to a concentration of 0.1 mM. The combination of 0.1 mM sodium peroxodisulfate and irradiation showed a slight radiosensitizing effect with an enhancement factor of up to 1.5. This was coupled with an increase in apoptosis from 12 to 22% and an inhibition of repair of irradiation-induced DNA damage. Incubation with concentrations between 0.1-1.0 mM sodium peroxodisulfate resulted in a strong decrease of clonogenic survival with an IC50 of 0.28 mM. This was correlated with an increase in cross links. Furthermore, a strong additive effect was observed for the combination of 0.3 mM sodium peroxodisulfate and irradiation resulting in an increase in enhancement ratio from 1.3 at 2 Gy to 3.1 at 6 Gy (p</=0.08). However, no further increase in apoptosis was detected. Our results implicate sodium peroxodisulfate to be a potentially useful agent to improve the radiobiological efficacy in radioresistant soft tissue sarcomas as exemplified for the cell line US8-93.

Apoptosis↗