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Biomedical subjects

D Rohde

Publications and source records attributed to D Rohde.

At least 19 recordsLinked to original sources

[Recurrent disease in renal cell carcinoma. "Local recurrence" after kidney-sparing and radical resection].

Locally recurrent renal cell carcinoma (RCC) is 0-10% after nephron-sparing surgery, 2.5-4% after thermoablative interventions and 2-3% after (radical) nephrectomy. Risk-factors are: sporadic or hereditary origin, tumor size, multifocality, histologic phenotype and incomplete resection. To date, there are no significant differences in the incidence of locally recurrent tumors independently of whether open or laparoscopic techniques were preferred. Caution still has to be taken with the use of alternative tools for minimally invasive tumor ablation.Finally, no statistically proven standard therapy exists that would clearly provide a superior outcome for patients with an isolated local recurrence. However, meta-analyses strongly support the performance of a resection of the recurrence as the primary working principal.

Carcinoma, Renal Cell↗

[Urogenital cancer studies in view of new legislation].

Harmonization of European GCP-V-related decrees crushed German urogenital cancer study activities and has led to complete discontinuation of investigator-initiated studies since August 2004. For renal cell carcinoma, the two major branches of the German cancer society (Deutsche Krebsgesellschaft e.V.), the Association for Urogenital Oncology (AUO) and the Association for (Internal) Medical Oncology (AIO), founded a Renal Cancer Task Force Group composed of the active members of the former "Intergroup Competence Network Renal Carcinoma" (IKN-N) in the spring of 2004. The resulting intergroup consortium represents an overall community of more than 100 German clinical departments that are highly experienced in oncological studies and ready to go for future trials. The basic ideas of the concept were transparency, multilateral consultations within the Task Force, and early involvement of national and international representatives of pharmaceutical companies and medical care insurance providers in the process of future study developments. Therefore, two pharmaceutical hearings took place at the University of Frankfurt.

Advisory Committees↗

[Renal cancer study activities in Germany. Drug therapy].

Drug therapy of advanced renal cell carcinoma underwent rapid changes. Monotherapeutic, placebo-controlled protocols -- and more recently combinations of different targeted drugs -- dominated the global clinical studies in the past 2 years. The preliminary results are almost encouraging and international investigators, supported by the pharmaceutical industry, were most successful in enrolling patients quickly. The present article reviews the recent German drug study activities and indicates potential future projects.

Antineoplastic Agents↗

[New targets and drugs for treatment of advanced renal cell carcinoma].

Conventional immunotherapeutic approaches have failed to achieve fundamental benefits for clinical outcome of patients with advanced metastatic renal cell carcinoma (MRCC). New, encouraging substances have gained broad access to the field of oncology and have already shown most promising preliminary results in patients with MRCC. Of mayor interest are antibodies and (receptor) tyrosine kinase inhibitors that are targeted against growth-factor receptors (of vascular endothelial and/or tumor cells). Single or multi-drug regimens are under way and are soon to be marketed.

Antibodies, Monoclonal↗

Percutaneous radiofrequency ablation of renal cell carcinoma: preliminary results.

PURPOSE: To report early results in percutaneous radiofrequency ablation (RFA) of renal cell carcinoma with an expandable RF probe. MATERIAL AND METHODS: In 14 patients (9 male, mean age 67.9 +/- 9.9 years) CT-guided percutaneous radiofrequency ablation of 15 renal cell carcinomas was performed using an expandable LeVeen probe (diameter 2-4 cm) and a 200-watt generator under general anesthesia and CT control. Tumors exceeding a diameter of 3 cm (n=6) were embolized within 24 h prior to RFA. Average tumor size was 3.0 +/- 1.0 cm. RESULTS: RFA was technically successful in all patients, resulting in a mean size of necrosis of 3.7 +/- 0.7 cm. With the exception of one reno-cutaneous fistula, which was successfully treated conservatively, no major complications were observed. No local recurrence was observed (follow-up: 13.9 +/- 12.4 months) while extrarenal tumor progression occurred in four patients. CONCLUSION: Our preliminary data suggest that nephron sparing percutaneous RFA of renal tumors with an expandable RF probe is safe and effective.

Aged↗

[AUO Urogenital Cancer Studies].

Quality assessment of oncological studies is mandatory. The German Cancer Society (Deutsche Krebsgesellschaft) and its affiliated organizations attained the mayer role for such purposes. The present paper demonstrates that the Association of Urological Oncoloy (AUO), which is part of the German Cancer Society, became the most widely accepted and integrative workinggroup on urogenital cancers in Germany (97 studies). The AUO does not only provide the largest public data base on urogenital cancer studies (65 items, http: www.auo-online.de) - with 18 open studies presented in the paper - but also serves as the principal driving force for interdisciplinary urogenital cancer networks and international intergroup activities (AUO/EORTC).

Clinical Trials as Topic↗

Nephron-sparing percutaneous ablation of a 5 cm renal cell carcinoma by superselective embolization and percutaneous RF-ablation.

PURPOSE: To report on the nephron-sparing, percutaneous ablation of a large renal cell carcinoma by combined superselective embolization and percutaneous radiofrequency ablation. MATERIALS AND METHODS: A 5 cm renal cell carcinoma of a 43-year-old drug abusing male with serologically proven HIV, hepatitis B and C infection, who refused surgery, was superselectively embolized using microspheres (size: 500 - 700 microm) and a platinum coil under local anesthesia. Percutaneous radiofrequency ablation using a 7 F LeVeen probe (size of expanded probe tip: 40 mm) and a 200 Watt generator was performed one day after transcatheter embolization under general anesthesia. RESULTS: The combined treatment resulted in complete destruction of the tumor without relevant damage of the surrounding healthy renal tissue. The patient was discharged 24 hours after RF ablation. No complications like urinary leaks or fistulas were observed and follow up CT one day and 4 weeks after the radiofrequency intervention revealed no signs of residual tumor growth. CONCLUSION: The combined transcatheter embolization and percutaneous radiofrequency ablation of renal cell carcinoma has proved technically feasible, effective, and safe in this patient. It may be offered as an alternative treatment to partial or radical nephrectomy under certain circumstances.

Adult↗

Interstitial fluid pressure is increased in renal cell carcinoma xenografts.

The purpose of this study was to test the hypothesis that renal cell carcinoma (RCC) exhibits an increased intratumoral interstitial fluid pressure (IT-IFP). Therefore, resected tumors from human primary (n = 23) or metastatic RCC (n = 3) were xenografted in SCID mice. The IFP of single tumor nodules (n = 65) and normal mouse tissue (n = 195) was measured by means of the "wick-in-needle" technique. Data demonstrate that the mean IT-IFP at neoplasia was 35 times greater than in normal tissue, and decreased precipitously at the tumor boundary. IT-IFP values tended to increase with the grade of malignancy of the tumor cells and tumor size. The mean IT-IFP of xenografts derived from primary RCC was twice as high as that from metastatic RCC tissue. These findings indicate a biophysical barrier to drug delivery in RCC; this may, in concert with cellular-based drug resistance mechanisms, be an additional explanation for resistance of the tumor to certain blood-borne anticancer therapies.

Animals↗

7-N-(2-([2-(gamma-L-glutamylamino)-ethyl]-dithio)-ethyl)-mitomycin C (KW-2149) is more active than mitomycin C on chemonaive and drug-resistant urothelial carcinoma cells.

This in vitro study aimed to investigate the cytotoxic activity of 7-N-(2-([2-(gamma-L-glutamylamino)ethyl]dithio)ethyl)-mitomycin C (KW-2149) versus mitomycin C (MMC) against cell lines from human transitional cell carcinoma (TCC). Direct cytotoxicity of the two drugs was measured employing a colorimetric cytotoxicity assay on chemonaive and chemoresistant cancer cell populations. The results revealed that all cell lines (n = 19) were significantly more inhibited by treatment (2 h, 96 h) with KW-2149 than by MMC (P < 0.03-0.001). pH 6.0 decreased the stronger activity of KW-2149 (P < 0.013-0.004). Creatinine > or =10 mmol/l and nitrosourea > or =100 mg/l also inhibited the activity of KW-2149 significantly. Tumor cells with relative drug-resistance against MMC (RT112-MMC: 55-fold) exerted minor cross-resistance to KW-2149 (fourfold). In conclusion, the present in vitro data suggest KW-2149 to be a superior drug for intravesical therapy of patients with primary or recurrent superficial bladder carcinoma. Since pH and concentrations of creatinine and nitrosourea influence the activity of KW-2149, patients are supposed to profit from neutralizing the urinary pH and enhanced diureses.

Anti-Bacterial Agents↗

Induction of drug-resistant bladder carcinoma cells in vitro: impact on polychemotherapy with cisplatin, methotrexate and vinblastine (CMV).

Residual tumor, tumor progression or relapse after chemotherapy of patients with advanced or metastasized transitional cell carcinoma of the bladder (TCCB) are suggested to reflect intrinsic drug resistance of cancer cells, or the development of chemotherapy-resistant tumor cell populations. The present study aimed to establish drug-resistant subculture cell lines from human TCCB, selected for anticancer drugs, administered in the cisplatin, methotrexate and vinblastine (CMV) polychemotherapy protocol. Tumor cells from chemonaive cell lines of human TCCB (HT1376, TCCSUP) have been exposed to progressively increasing concentrations of cis-diamminedichloroplatinum (II) (CDDP), methotrexate (MTX), vinblastine (VBL) or etoposide (VP16). The resulting drug-resistant subculture cell lines (HT1376-CDDP, HT1376-MTX, HT1376-VBL, HT1376-VP, TCCSUP-CDDP, TCCSUP-MTX, TCCSUP-VBL, TCCSUP-VP) were analyzed with regard to the achieved resistance factor (RF) for the inductive anticancer agent, the acquisition of cross-resistance, DNA content, cell cycle distribution and cellular morphology. Parental HT1376 cells were intrinsically less sensitive to all anticancer drugs (1.7-50x), compared with TCCSUP cells. Relative resistance against the inductive anticancer agents was similar for the final drug-resistant subculture cell lines of both parental cell lines concerning CDDP and VP-16 (RF: 4-5x), but were reciprocal for MTX and VBL, respectively. MTX led to much stronger resistance (RF > 200) than the other drugs (RF < 10). Pleiotropic cross-resistances were observed in six out of eight (75%) drug-resistant subculture cell lines. Highest RF (50-500x) and frequency of cross-resistance (five of six cell lines) occured for MTX, and the least from exposure to CDDP (one of six cell lines). Overall, the results corroborated the central role of CDDP against urothelial carcinoma whereas repetitive applications of MTX appeared to be a doubtful strategy. Moreover, the experiments provide the largest panel so far of drug-resistant cell lines of human TCCB. They represent an appropriate tool for basic research on drug-resistance mechanisms, for the development and screening of future anticancer drugs or to elaborate strategies to overcome drug resistance for those patients who ultimately fail to respond to standard chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗