ABSTRACT
The reprocessing of medical products is an important topic both in urological practices and in hospitals. The complexity is caused by the increasing variety of medical instruments and also by the increasing demands on the legally required quality of the reprocessing. The Robert Koch Institute (RKI) and the Federal Institute for Drugs and Medical Devices (BfArM) have published recommendations for the processing of MD and last updated them in 2012. This article summarizes the legal framework for the reprocessing of medical devices, how medical devices are categorized before the appropriate procedure for reprocessing can be selected and the various steps in the reprocessing. A special focus is placed on medical products that are typically found in urological practices or outpatient departments and are processed there. Furthermore, the necessity of validating the processing method and the required training (expertise) of the personnel are discussed.
Subject(s)
Cross Infection , Equipment and Supplies , Hygiene , Sterilization , Hospitals , Endoscopy , Cross Infection/prevention & controlABSTRACT
INTRODUCTION: The aim of this study was to examine how the survival rates for patients with muscle-invasive bladder carcinoma are influenced by the tumor stage at initial presentation. PATIENTS AND METHODS: This study examined the clinical course of 452 patients who underwent radical cystectomy for bladder carcinoma from 1992 to 2004. The patients were divided into three groups according to the histological results of the initial and final transurethral tumor resection (TURB). In group 1 (n=114) patients who presented with a superficial bladder carcinoma which had a high likelihood of progressing underwent radical cystectomy. Group 2 included (n=92) patients who displayed a superficial tumor stage when they first presented and developed progressive muscle-invasive bladder carcinoma under conservative treatment. Group 3 (n=246) comprised patients who were already at the muscle-invasive tumor stage in the course of primary TURB. The histopathological characteristics of all transurethral tumor resections and radical cystectomy were recorded. Progression-free survival rates and overall survival rates in the three groups were then compared. RESULTS: The average patient age at cystectomy was 64.3 (35-80) years, and the average follow-up period was 49 months. Progression-free survival and overall survival of all 452 patients were 56.1 and 53.6%, respectively, after 5 years. The best outcome was a progression-free 5-year survival rate of 78.4% with organ-confined, lymph node-negative tumors (n=213). This result was statistically significant (p<0.01) compared with the progression-free 5-year survival rate of 42.3% for non-organ-confined, lymph node-negative tumors (n=112). Lymph node-positive patients (n=127) achieved a progression-free 5-year survival rate of 29.0% regardless of the tumor infiltration. Group 1 patients achieved a progression-free survival rate of 71.3% and an overall survival rate of 69.1% after 5 years. Group 2 patients achieved a progression-free survival rate of 52.9% and an overall survival rate of 51.4% after 5 years. Group 3 patients achieved a progression-free survival and overall survival of 50.2% and 47.1%, respectively, after 5 years. There was no significant difference between groups 2 and 3 with regard to their progression-free or overall survival rates (p>0.45). However, both groups displayed significantly poorer progression-free and overall survival rates compared with group 1 (p<0.01). CONCLUSION: Our results show that patients with superficial bladder carcinoma with tumor progression to muscle invasion do not have a better prognosis after radical cystectomy than patients presenting initially with muscle-invasive bladder carcinoma. Survival rates in this group can only be improved by singling out patients on the basis of risk factors at an earlier stage and carrying out cystectomy. Due to these results we must expect that waiting for a muscle invasion in patients with superficial bladder carcinoma with a high risk profile results in a significant impairment of prognosis.
Subject(s)
Carcinoma, Transitional Cell/surgery , Cystectomy , Urinary Bladder Neoplasms/surgery , Aged , Biopsy , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Cystoscopy , Disease Progression , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Retrospective Studies , Survival Rate , Urinary Bladder/pathology , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathologyABSTRACT
Absolute and relative (ratio absolute tumor volume to gland volume) tumor volumes were visually estimated in 528 prostatectomy specimens. Surveying a mean post-surgical follow-up of 49 months, both parameters were analyzed regarding their aptitude for prognostication. We found relative tumor volumes exceeding 25% to independently predict biochemical recurrence reflected by post-surgical prostate-specific antigen progression, which was also determined to be increased to 28% when absolute tumor volumes exceeded 10 cm(3). However, this cutoff failed to be an independent prognosticator. Because the visual estimation of both parameters can easily be performed, they are felt to be formidable candidates for deriving prognostic information during routine procedures.
Subject(s)
Carcinoma/diagnosis , Diagnostic Techniques and Procedures , Prostatectomy , Prostatic Neoplasms/diagnosis , Tumor Burden , Adult , Aged , Carcinoma/blood , Carcinoma/pathology , Carcinoma/surgery , Disease-Free Survival , Humans , Male , Middle Aged , Prognosis , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Treatment OutcomeABSTRACT
OBJECTIVE: We present an external validation study investigating the applicability of the preoperative Kattan nomogram for predicting recurrence after prostatectomy in a population of patients with serum prostate-specific antigen (PSA) levels exceeding 20 ng/ml. MATERIALS: In the evaluation of clinical parameters pooled from a total of 191 patients presenting with PSA levels ranging between 20.1 and 100 ng/ml, the PSA-free survival rate 60 months after surgery was calculated according to Kattan nomograms. Subsequently, the results were statistically compared with the corresponding actual survival rates obtained from Kaplan-Meier analysis. For this purpose, the patients were assigned to one of four different risk groups according to predictions derived from the Kattan nomograms, enabling a direct comparison of expected (as predicted by Kattan nomogram) versus actual survival of each patient investigated in our study. RESULTS: Predicted PSA-free survival rates were determined to be as follows: 83% (low risk group); 66% (intermediate risk group); 39% (intermediate-high risk group), and 10% (high risk group) in comparison with the actual survival rates determined to be 63, 62, 40 and 21%, respectively. For PSA levels ranging between 20.1 and 30 ng/ml, 30.1 and 50 ng/ml, and 50.1 and 100 ng/dl, PSA-free survival rates were found to be 57, 37, and 27% (p=0.0017), respectively, during a 5-year post-prostatectomy follow-up. CONCLUSIONS: The Kattan nomogram shows good statistical concordance with actual survival rates in the mean risk quadrants, but considerable differences were demonstrated concerning individuals with either a high or with a low risk of cancer progression.
Subject(s)
Biomarkers, Tumor/blood , Neoplasm Recurrence, Local/blood , Nomograms , Preoperative Care , Prostate-Specific Antigen/blood , Prostatectomy , Prostatic Neoplasms/surgery , Aged , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Predictive Value of Tests , Prognosis , Prostatic Neoplasms/blood , Retrospective StudiesABSTRACT
Several case reports and small case series have described a total of 66 patients with sarcoidosis and testicular cancer so far. This report describes three additional cases. We highlight the association of sarcoidosis and testicular cancer and comment on the potential impact of this connection on the interpretation of the radiological and pathological findings in suspected cancer relapse. Sarcoidosis, a condition that can be combined with testicular cancer, should always be considered in the differential diagnosis.
Subject(s)
Mediastinal Diseases/complications , Neoplasms, Germ Cell and Embryonal/complications , Sarcoidosis/complications , Seminoma/complications , Testicular Neoplasms/complications , Adult , Biopsy , Diagnosis, Differential , Humans , Lymph Node Excision , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Male , Mediastinal Diseases/pathology , Mediastinal Diseases/surgery , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/surgery , Orchiectomy , Postoperative Complications/diagnosis , Postoperative Complications/pathology , Postoperative Complications/surgery , Sarcoidosis/pathology , Sarcoidosis/surgery , Sarcoidosis, Pulmonary/complications , Sarcoidosis, Pulmonary/pathology , Sarcoidosis, Pulmonary/surgery , Seminoma/pathology , Seminoma/surgery , Testicular Neoplasms/pathology , Testicular Neoplasms/surgery , Testis/pathology , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE: To investigate whether the differentiated resection technique for excising superficial bladder cancer leads to higher recurrence and progression rates as compared with regular resection. SUBJECTS AND METHODS: We evaluated 163 patients, 66 undergoing a differentiated and 97 a regular resection. All patients underwent a routine second resection within 6-10 weeks. Recurrence and progression rates as well as tumour persistence on second resection were analyzed. RESULTS: Patients with differentiated resections of bladder tumours did not have higher tumour recurrence and progression rates. Also, these patients had a significantly higher percentage of tumour-free second resections (p = 0.03). CONCLUSION: The differentiated resection technique for excising superficial bladder cancer has no negative influence on recurrence and progression rates, but it leads to a reduced tumour persistence.
Subject(s)
Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/surgery , Cystectomy/methods , Neoplasm Recurrence, Local/pathology , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgery , Aged , Carcinoma, Transitional Cell/mortality , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Neoplasm, Residual , Retrospective Studies , Survival Rate , Treatment Outcome , Urinary Bladder Neoplasms/mortality , Video-Assisted SurgeryABSTRACT
Although neoadjuvant, antihormonal therapy does not lead to an improvement in the outcome of prostatic carcinoma it is still used in the short-term in a subset of patients. Here we report the regressive changes due to this short-term treatment and analyse the impact on Gleason grading. The most frequent regressive changes in 82 tumors treated short-term were determined and quantified. The results were compared to a matched control group and also to the preoperative needle biopsies.A steep increase in regressive changes was observed within the first 4 weeks. After this point, changes increased only mildly. Within the first 2 weeks of treatment no significant changes compared to control tissue were present. Compared to the preoperative needle biopsies, pretreated tumors showed a significant upgrading. After 2 weeks of neoadjuvant antihormonal therapy, regressive changes are so great, that Gleason grading can no longer be recommended.
Subject(s)
Hormone Antagonists/toxicity , Prostate/pathology , Prostatic Neoplasms/pathology , Biopsy, Needle , Chemotherapy, Adjuvant , Hormone Antagonists/therapeutic use , Humans , Male , Prostate/drug effects , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/surgery , Retrospective StudiesABSTRACT
Intensity modulated radiotherapy (IMRT) combined with recently developed noninvasive image-guided targeting techniques for tumor localization/repositioning provide a means to further improve on conformal radiotherapy of prostate cancer by optimally sparing the rectum. This refined approach may potentially improve treatment results for locally advanced prostate cancer while reducing side effects. This review summarizes the clinical requirements for effective prostate radiotherapy and describes the new technology that helps to better fulfil these requirements. These noninvasive developments, their potential benefit as well as their limitations, together with new data on fractionation sensitivity of prostate cancer that may lead to shortened overall treatment times may be of interest for all physicians treating patients with prostate cancer.
Subject(s)
Image Interpretation, Computer-Assisted/methods , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/radiotherapy , Radiometry/methods , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Conformal/methods , Humans , Male , Radiotherapy Dosage , Radiotherapy, Computer-Assisted/methodsABSTRACT
INTRODUCTION: Approximately 5 - 7 % of germ cell tumors are of extragonadal origin. Biology and genetics are unclear, especially when the primary location is in the retroperitoneum. Chemotherapy is the initial treatment of choice for extragonadal germ cell tumors (EGGCTs), followed by surgical resection of the residual tumor mass. A primary testicular tumor must be ruled out by sonographic investigation and biopsy. The rate of metachronous testicular cancer in men with primary EGGCT is largely unknown. CASE REPORT: We present the first patient in the literature who developed a metachronous testicular cancer 10 months after primary occurrence of EGGCT in the retroperitoneum. CONCLUSIONS: This case report emphasizes the importance of follow-up examinations of patients with primary EGGCTs. They should include careful sonographic investigation of the testis in order to detect metachronous testicular cancer early. Suspicious findings require open surgery biopsy. Intraoperative histopathology can be false-negative for cancer detection, as an immunohistochemical examination is not available.
Subject(s)
Carcinoma in Situ/diagnosis , Neoplasms, Germ Cell and Embryonal/diagnosis , Neoplasms, Second Primary/diagnosis , Retroperitoneal Neoplasms/diagnosis , Testicular Neoplasms/diagnosis , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bleomycin/administration & dosage , Carcinoma in Situ/drug therapy , Carcinoma in Situ/pathology , Carcinoma in Situ/surgery , Cisplatin/administration & dosage , Combined Modality Therapy , Diagnostic Imaging , Etoposide/administration & dosage , Humans , Male , Neoadjuvant Therapy , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/surgery , Neoplasms, Second Primary/drug therapy , Neoplasms, Second Primary/pathology , Neoplasms, Second Primary/surgery , Orchiectomy , Reoperation , Retroperitoneal Neoplasms/drug therapy , Retroperitoneal Neoplasms/pathology , Retroperitoneal Neoplasms/surgery , Testicular Neoplasms/drug therapy , Testicular Neoplasms/pathology , Testicular Neoplasms/surgery , Testis/pathologyABSTRACT
PURPOSE: Accurate imaging is essential for correct operative planning and successful surgical intervention in renal cell carcinoma (RCC). Our objective was the comparison of color duplex sonography with spiral computed tomography (CT) and surgical-pathological findings in the evaluation of renal masses to determine tumor localization, size, tumor thrombus extent and lymph node metastases. METHODS: We evaluated 60 patients with a renal mass in a prospective study. Both color duplex sonography and CT were performed by different investigators without knowledge of the supposed diagnosis. The color Doppler findings were compared to CT and surgical pathological findings. RESULTS: The sensitivity of color duplex sonography in the detection of RCC and lymph node metastases is comparable to that of CT (100%). Color duplex sonography was superior in the detection of renal vein involvement. Color duplex sonography alone allowed correct planning of the surgical procedure without intraoperative changes in all patients. CONCLUSION: Duplex sonography provides exactly the same information as CT. Although duplex sonography is less expensive with lower exposure to radiation, most surgeons will still probably demand CT for diagnosis, especially as this method is unerring and duplex sonography highly depends on the expertise of the person using it.
Subject(s)
Carcinoma, Renal Cell/diagnosis , Kidney Neoplasms/diagnosis , Tomography, X-Ray Computed , Ultrasonography, Doppler, Color , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Preoperative Care , Reproducibility of ResultsABSTRACT
LDR Brachytherapy, a Minimally Invasive Alternative in the Treatment of Organ-Confined Prostate Cancer In den letzten Jahren erlebte die Brachytherapie mit permanenten Implantaten beim organbegrenzten Prostatakarzinom besonders in den USA, wo im Jahre 1999 mehr als 40 000 Implantationen durchgeführt wurden, eine Renaissance. Mit einer gewissen Verzögerung nimmt die Popularität dieser Methode auch in Europa immer mehr zu. Dies, obwohl die Brachytherapie keine absolut neue Methode in der Behandlung des Prostatakarzinoms ist, sie hat im Gegenteil eine lange Tradition.
Subject(s)
Brachytherapy , Prostatic Neoplasms/radiotherapy , Clinical Trials as Topic , Humans , Male , Neoplasm Staging , Prostate-Specific Antigen/blood , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Radiotherapy DosageABSTRACT
PURPOSE: Urinary diversion with percutaneous nephrostomy or ureteral stent is indicated by symptoms, such as persistent colic, high temperature and uremia, of hydronephrosis caused by stones. We evaluate which of these 2 methods is superior concerning the course of procedure, relief of accompanying symptoms and quality of life in regard to patient age and sex. MATERIALS AND METHODS: A total of 40 patients with stone induced hydronephrosis were randomized into either percutaneous nephrostomy or stent insertion groups. These patients were then evaluated by procedure (use of analgesics, x-ray exposure, success of insertion), relief of accompanying symptoms (duration of diversion, intravenous administration of antibiotics for high temperature) and quality of life (questionnaire immediately and 2 to 4 weeks postoperatively). RESULTS: Two comparable groups of patients were formed, with an average age of 55 versus 49 years and a male-to-female ratio of 12:8 versus 9:11 for those who underwent percutaneous nephrostomy versus those who received a stent, respectively. Percutaneous nephrostomy was successfully completed in 100% of patients and stents were successful in 80%, with a 20% conversion to percutaneous nephrostomy. The x-ray exposure was shorter in the percutaneous nephrostomy group (p = 0.052). Administration of analgesics was more frequent in the stent group (p = 0.061). Percutaneous nephrostomy indwelling time was shorter (50% less than 2 weeks) than that of stents (25% less than 2 weeks, p = 0.043). Antibiotics were administered for greater than 5 days in 0% of patients who underwent percutaneous nephrostomy versus 64% in those with stents (p = 0.174). Reduction in quality of life was moderate but more pronounced in patients with stents compared to those who underwent percutaneous nephrostomy, and was more distinct in males and younger patients. The quality of life progressively improved in the course of diversion with percutaneous nephrostomy but deteriorated with stents. CONCLUSIONS: Our results demonstrated that percutaneous nephrostomy is superior to ureteral stents for diversion of hydronephrosis caused by stones, especially in patients with a high temperature, as well as in males and juveniles.
Subject(s)
Hydronephrosis/surgery , Nephrostomy, Percutaneous , Stents , Urinary Diversion/methods , Adult , Female , Humans , Hydronephrosis/etiology , Male , Middle Aged , Prospective Studies , Quality of Life , Treatment Outcome , Urinary Calculi/complicationsABSTRACT
Neuroendocrine (NE) differentiated tumor cells are found in almost all prostatic carcinomas. Prostatic carcinomas with a high NE differentiation have a poor prognosis and increased metastatic potential. A relationship between the neovascularisation density in the tumor and the metastatic potential in prostatic carcinoma is well known. NE cells and microvessels were demonstrated immunohistochemically on 102 radical prostatectomy specimens using antibodies against Chromogranin A and CD34. Standard areas (7.9 mm2) of maximal Chromogranin A expression and highest vascularisation were determined and topographically related by light microscopy. Area density of microvessels was evaluated morphometrically. NE tumor cells were present in all prostatic carcinomas studied. High grade prostatic carcinomas expressed significantly more NE tumor cells and exhibited a higher neovascularisation than low grade carcinomas. There was significantly higher neovascularisation in high grade tumors with many, as compared to high grade tumors with few, NE tumor cells. Poorer pathological staging correlated with increased neovascularisation and stronger NE differentiation. A topographical relationship between the area of maximal NE tumor cells and the area of highest neovascularisation was found in 80.4% of all cases. An analysis of variance revealed a large number of NE tumor cells as the only predictor of an increased neovascularisation (p = 0.0006). These observations support the concept that increased neovascularisation is influenced not only by poor pathological grading but also by a high NE differentiation.
Subject(s)
Adenocarcinoma/blood supply , Neovascularization, Pathologic/pathology , Neurosecretory Systems/pathology , Prostatic Neoplasms/blood supply , Adenocarcinoma/chemistry , Adenocarcinoma/secondary , Adenocarcinoma/surgery , Aged , Antigens, CD34/analysis , Biomarkers, Tumor/analysis , Cell Differentiation , Chromogranin A , Chromogranins/analysis , Endothelium, Vascular/chemistry , Endothelium, Vascular/pathology , Humans , Immunoenzyme Techniques , Male , Microcirculation , Prostatic Neoplasms/chemistry , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgeryABSTRACT
Cisplatin is one of the most potent cytotoxic drugs and in chemotherapy has ameliorated numerous tumors. Nevertheless, resistance to cisplatin is a problem that is encountered in the chemotherapy of urologic tumors, especially transitional cell carcinomas. In order to improve definition of the mechanisms of cisplatin-resistance we established a series of cisplatin-resistant sublines from the cell line RT 112 in increasing concentrations of cisplatin. The most resistant subline CP3 is approximately 10 times more resistant than the parental line and shows a 10-fold cross-resistance against methotrexate, whereas vinblastine and doxorubicin are equally effective in the parental and sublines. Combined treatment of CP3 cells with cisplatin and buthionine sulfoximine (BSO) does not result in enhanced cell kill, thereby ruling out glutathione as a resistance mechanism. However, in comparison with parental cells, CP3 cells are about 1.5 times more resistant against cadmium. On the protein level, the cisplatin-resistant cells reveal an enhanced expression of metallothionein II (MTII), but not MTI, suggesting that the cisplatin resistance we observed in these sublines is at least partly mediated by MTII. These sublines will in the future serve as valuable tools for the analysis of cisplatin resistance, especially in view of metallothionein-mediated resistance mechanisms.
Subject(s)
Antineoplastic Agents/pharmacology , Cisplatin/pharmacology , Metallothionein/metabolism , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/metabolism , Buthionine Sulfoximine/pharmacology , Cadmium/pharmacology , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/metabolism , Cell Division/drug effects , Doxorubicin/pharmacology , Drug Resistance , Drug Resistance, Multiple , Glutathione/metabolism , Humans , Methotrexate/pharmacology , Tumor Cells, Cultured , Vinblastine/pharmacologyABSTRACT
To characterize the clinical relevance of MRP gene in the chemoresistance of prostate carcinomas we determined the multidrug resistance-associated protein (MRP) expression in 30 samples from organ-confined prostate carcinoma, 9 samples from adjacent normal tissue and 4 hormone unresponsive cancers. The measurement of MRP expression was carried out by reverse transcription polymerase chain reaction (RT-PCR) in combination with capillary electrophoresis. Incorporated fluorescence-labeled primers were disclosed by a laser-operated fluorescence detection module. MRP expression was quantified by integration of the peak area and correlated to the ubiquitously expressed beta2 microglobulin. As positive control served the adriamycin-resistant HL60-ADR cell line, which overexpresses MRP. MRP expression was found in all samples. All samples showed a lower MRP/beta2 ratio than HL60-ADR cells. The expression of the MRP gene was 30% higher in organ-confined tumors than in hormone-unresponsive anaplastic tumors. Normal tissue showed the same MRP mRNA level as the adriamycin-sensitive HL60 cells. A higher tumor stage correlated with an increase of MRP expression (> factor 2), whereas G3 tumors displayed a MRP expression 30% lower than in G2 tumors. The small alterations indicate that MRP expression seems not be involved in the chemoresistance of prostate carcinomas.
Subject(s)
ATP-Binding Cassette Transporters/genetics , Drug Resistance, Multiple/genetics , Prostate/metabolism , Prostatic Neoplasms/genetics , Antineoplastic Agents/pharmacology , Base Sequence , DNA Primers/genetics , Gene Expression , HL-60 Cells , Humans , Male , Multidrug Resistance-Associated Proteins , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
OBJECTIVE: We evaluated the cytotoxic activity of the three anthracyclines, doxorubicin, epirubicin and idarubicin, in different sublines of the Dunning rat prostate carcinoma as well as in multidrug-resistant KB cells, expressing a high amount of the human multidrug resistance gene product, P glycoprotein. METHODS: The effectiveness of the three anthracyclines was tested in vitro in the Dunning rat prostate carcinoma sublines G, AT.1, AT.3.1, MatLu, and MatLyLu, as well as in multidrug-resistant KB cells, using an MTT assay. RESULTS: All drugs were clearly more effective in the androgen-sensitive Dunning rat prostate carcinoma subline G than in the androgen-independent growing sublines AT.1, AT.3.1, MatLu, and MatLyLu. Idarubicin was much more effective than doxorubicin or epirubicin. To further elucidate the mechanism of action of idarubicin as compared with doxorubicin and epirubicin, we tested the cytotoxicity of these anthracyclines in highly multidrug-resistant KB-V1 cells, which express high amounts of P glycoprotein, as well as in the drug-sensitive parental KB-3-1 cells. KB-V1 cells proved to be highly resistant to doxorubicin and epirubicin with IC50 values of 2,300 and 1,000 ng/ml, respectively. Idarubicin, however, was about 57.5-fold and 25-fold more active, respectively, suggesting, that it is able to overcome P-glycoprotein-mediated multidrug resistance. CONCLUSION: The strong in vitro effectiveness of idarubicin in androgen-insensitive prostate carcinoma cells suggests that this drug might be useful in the treatment of hormone-refractory prostate carcinoma.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Carcinoma/drug therapy , Doxorubicin/pharmacology , Epirubicin/pharmacology , Idarubicin/pharmacology , Prostatic Neoplasms/drug therapy , ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis , Animals , Antibiotics, Antineoplastic/therapeutic use , Carcinoma/pathology , Carcinoma/secondary , Cell Division/drug effects , Doxorubicin/therapeutic use , Drug Resistance, Multiple , Epirubicin/therapeutic use , Humans , Idarubicin/therapeutic use , KB Cells/cytology , KB Cells/drug effects , Lethal Dose 50 , Male , Prostatic Neoplasms/pathology , Rats , Tumor Cells, CulturedABSTRACT
Prostate carcinomas are in general resistant against virtually all cytotoxic drugs. Up to now it has not been thoroughly evaluated whether specific resistance factors, such as the expression of the MDR1 gene, play a role in this multi-agent resistance and whether there is a link between drug resistance and hormone-independent growth. We investigated the resistance patterns of a hormone-sensitive and four hormone-independent Dunning rat carcinoma sublines against four drugs which are substrates of P-glycoprotein (vinblastine, taxol, doxorubicin, and etoposide) and two agents (methotrexate and cis-platinum) which are not transported by this efflux pump. All hormone-insensitive sublines, AT.1, AT. 3.1., MatLu and Mat LyLu, continuously showed a clearly enhanced resistance (3- to 26-fold) against the P-glycoprotein substrates, compared to the hormone-sensitive subline G. Only two of the androgen-independent sublines displayed enhanced resistance against methotrexate, whereas all of them were more sensitive against cisplatin than the androgen-sensitive G cells. By addition of verapamil the resistance against vinblastine (9- to 10-fold) and taxol (6.7- to 26.7-fold) in the hormone-insensitive cells could be almost totally reversed. Furthermore, the fluorescent P-glycoprotein substrate rhodamine-123 was effectively pumped out of the four tested hormone-independent cell lines, whereas the hormone-sensitive G cells were unable to extrude the dye. By reverse transcriptase polymerase chain reaction (RT-PCR) with primers specific for the rat mdr1b gene, the homologue to the human MDR1 gene, we could easily detect mdr1b expression in the androgen independent cell lines, but not in the G cells. Our results suggest that the product of the rat mdr1b gene is involved in the multidrug resistance of androgen-independent Dunning prostate carcinoma cells.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/physiology , Antineoplastic Agents/pharmacology , Drug Resistance, Multiple , Drug Resistance, Neoplasm/physiology , Genes, MDR/physiology , Prostatic Neoplasms/drug therapy , Androgens/pharmacology , Animals , Antibiotics, Antineoplastic/pharmacology , Antimetabolites, Antineoplastic/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Doxorubicin/pharmacology , Etoposide/pharmacology , Fluorescent Dyes/pharmacology , Male , Methotrexate/pharmacology , Neoplasms, Hormone-Dependent/drug therapy , Paclitaxel/pharmacology , Rats , Rhodamine 123 , Rhodamines/pharmacology , Tumor Cells, Cultured/drug effects , Verapamil/pharmacology , Vinblastine/pharmacologyABSTRACT
Multidrug resistance of tumor cells is a well-known phenomenon in oncology. Among the substances excluded from the cells are not only antineoplastic drugs but also certain antibiotics, e.g. erythromycin. To prove the hypothesis that this might render infections with intracellular bacteria untreatable with these antibiotics we used erythromycin to treat intracellular infection of multidrug resistant (MDR) cells with Listeria monocytogenes. Erythromycin was unable to restrict the growth of L. monocytogenes in KBV-1 MDR cells in concentrations of up to 25 micrograms/ml. In contrast, 0.049 micrograms/ml of erythromycin were sufficient to restrict the growth of the bacteria in nonresistant KB 3-1 cells. When verapamil was added to the supernatant of KBV-1 cells, erythromycin regained its effectivity on L. monocytogenes multiplying in these cells. The fact that MDR cells may render intracellular bacteria inaccessible to certain antibiotics might have important implications for the persistence of these bacteria in the host and for the treatment of patients with genetically engineered MDR cells.