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Biomedical subjects

G Jakse

Publications and source records attributed to G Jakse.

At least 55 records · Page 3Linked to original sources

Cytochrome P450 isoenzyme mRNA expression pattern in human urinary bladder malignancies and normal urothelium.

This study was designed to analyze the cytochrome P450 isoenzyme mRNA expression pattern of transitional cell carcinomas of the bladder (N = 19) and normal urothelium (N = 10). In addition, biopsies from normal urothelium (N = 32) taken at the time of transurethral resection of bladder cancer in eight patients from surrounding histologically normal urothelium also were characterized concerning their specific cytochrome P450 mRNA expression pattern. A total of 13 of 19 of the analyzed tumor specimens (68%) revealed expression of cytochrome P450 1B1. Cytochrome P450 4B1 and 1A1 mRNA expression were detected in 79% (15 of 19) and 53% (10 of 19) of the tumor specimens, with no correlation between tumor stage and grade of the neoplasm. Biopsies from macroscopically and histologically normal urothelium from tumor-invaded bladders also showed expression of cytochrome P450 1B1 in 75% (24 of 32), 4B1 in 62.5% (20 of 32), and 1A1 in 50% (16 of 32). Furthermore, a 75% homology concerning cytochrome P450 1B1 and 4B1 mRNA expression was observed between the bladder tumor and the biopsies from this bladder. The polymerase chain reaction analysis of normal urothelium from normal bladders that do not harbor a neoplasm revealed CYP450 mRNA expression for CYP450 1A1 in 6 of 10; 1B1 in 5 of 10; 4B1 in 6 of 10; 2D6 in 2 of 10; and 2E1 in 2 of 10. According to our data, CYP450 1B1 mRNA expression is not tumor-specific. The present findings are the first to compare CYP450 expression in bladder cancer with biopsies from the same tumor-bearing bladder, and they indicate that, from the enzymatic point of view, bladder cancer also is a panurothelial field disease present in even normal urothelium.

Aged↗

[Radical perineal prostatectomy without lymphadenectomy. Patients with cT1 + 2, G1 +2, PSA < or = 10 ng/ml prostate carcinoma].

Pelvic lymphadenectomy in patients with organ confined prostate cancer (PCa) is of no therapeutic value and is questionable in many patients because of the low incidence of metastases. 49 patients with < or = cT2 b, G1 + 2, PSA < or = 10 ng/ml underwent laparocopic pelvine lymphadenectomy and radical perineal prostatectomy. Only 1 patient (2%) had microscopic metastases which were missed on frozen section. Because of these own results and those reported in the literature we then performed in patients with this constellation the radical perineal prostatectomy without lymphadenectomy (n = 32). The differences present in both groups concerning complication rate and morbidity are due to laparoscopic lymphadenectomy and the learning curve in perineal prostatectomy.

Aged↗

Does positron emission tomography using 18-fluoro-2-deoxyglucose improve clinical staging of testicular cancer?--Results of a study in 50 patients.

OBJECTIVES: To compare positron emission tomography (PET) using 18-fluoro-2-deoxyglucose (FDG) with conventional clinical staging in unselected patients with germ cell cancer. METHODS: Fifty patients underwent PET scans of the abdomen (n = 50) and chest (n = 41 ) after the initial diagnosis. PET images were evaluated qualitatively and quantitatively using standardized uptake values (SUVs). The results were compared with computed tomography (CT) results and tumor markers (human chorionic gonadotropin, alpha-fetoprotein, and lactate dehydrogenase). Retroperitoneal lymphadenectomy in 12 patients and clinical staging, including follow-up data in all patients, were taken as a reference standard. RESULTS: PET detected metastases in 13 (87%) of 15 patients and excluded metastases in 33 (94%) of 35 patients. A sensitivity of 73% and a specificity of 94% were obtained using CT. The respective values for tumor marker determination were 67% and 100%. Retroperitoneal metastases were detected in 2 patients by PET only and in 1 patient by CT only. In the latter patient, surgery of a residual mass after chemotherapy revealed a well-differentiated teratoma. False-negative findings with PET and CT occurred in 2 patients with retroperitoneal metastases approximately 10 mm in size. False-positive findings were due to sarcoidosis or to muscular activity of the neck. Quantitative FDG uptake was very heterogeneous, with an SUV ranging from 1.8 to 17.3. CONCLUSIONS: FDG PET has the potential to improve clinical staging of testicular cancer. However, PET, as well as CT, is limited in the detection of small retroperitoneal lymph node metastases.

Adult↗

Polyploidization and losses of chromosomes 1, 2, 6, 10, 13, and 17 in three cases of chromophobe renal cell carcinomas.

Clonal chromosome aberrations identified after short-term culture are presented for three cases of chromophobe renal cell carcinomas (RCC). All tumors revealed abnormal karyotypes with a varying proportion of polyploid tumor cells. Common numerical abnormalities were combined losses of chromosomes 1, 2, 6, 10, 13, and 17. Clonal karyotypic evolution was demonstrated in one case in which several related clones could be identified. An additional balanced translocation t(3;14)(p24;q22) observed in this case proved to be of constitutional nature by cytogenetic analysis of normal kidney cells and peripheral blood lymphocytes. These cytogenetic findings provide further evidence that chromophobe renal cell carcinomas are characterized by a highly specific combination of chromosomal losses most commonly including chromosomes 1, 2, 6, 10, 13, and 17.

Adenocarcinoma↗

Papillary renal cell carcinoma with clear cell cytomorphology and chromosomal loss of 3p.

AIMS: Cytogenetic studies on renal cell carcinomas (RCCs) have disclosed a correlation between chromosome aberrations and histomorphological features. Nevertheless, it is still controversial whether the cytomorphology of the tumour cells (clear cell, chromophilic, chromophobe) or their growth pattern (nonpapillary, papillary) is more discriminative for the combined histomorphological-cytogenetic classification of RCCs. METHODS AND RESULTS: Three RCCs with papillary growth pattern and clear cell cytomorphology were analysed by classical cytogenetics using standard G-banding techniques. Each tumour displayed clonal aberrations leading to loss of terminal 3p chromosomal segments. Monosomy 14 was also consistently found. Trisomy 17 was not observed in any of the tumours. CONCLUSIONS: This series of three RCCs consisting of clear cells with papillary architecture revealed chromosomal aberrations characteristic for the conventional (clear cell) RCC. Irrespective of the predominant papillary growth pattern, none of the cases were characterized by trisomy of chromosomes 3q, 7, 8, 12, 16, 17 and 20 and loss of Y chromosome which are widely regarded as the most consistent genetic alterations for papillary RCC. Therefore, our cytogenetic findings provide evidence that papillary clear cell RCCs should be classified according to their cytomorphology rather than their growth pattern even when papillary architecture is prominent.

Adult↗

Detection of prostate-specific antigen immunoreactivity in amniotic fluid.

OBJECTIVE: To examine whether prostate-specific antigen (PSA) is present in amniotic fluid, whether the amniotic fluid PSA concentration changes with gestational age, and whether there is an association between amniotic fluid PSA and fetal sex. METHODS: The PSA concentration was measured in the amniotic fluid of 48 pregnant women. Thirty-four samples were obtained during routine amniotic fluid analyses performed during gestational weeks 16-18, whereas 14 samples were obtained during cesarean section performed after gestational week 36. RESULTS: PSA was detected in all amniotic fluid samples. The median amniotic fluid PSA was 0.193 ng/ml during gestational weeks 16-18 and 0.39 ng/ml after gestational week 36 (p = 0.1). Furthermore, no significant association was seen between amniotic fluid PSA and fetal sex. The median amniotic fluid PSA level was 0.233 ng/ml for the 21 boys and 0.222 ng/ml for the 27 girls investigated (p = 0.72). CONCLUSIONS: These results confirm recent literature reports that PSA may serve as a growth regulator during normal fetal development. However, further studies are necessary to elucidate the exact role of PSA during fetal development.

Amniotic Fluid↗

Tumor-adopted diagnosis of bladder cancer.

70% of our patients suffering from bladder cancer present themselves initially with a superficial tumor (Tis, Ta, T1) and only 30% are initially seen with a muscle-invasive carcinoma (T2, T3-4, N+, M+). Clinical history, physical examination, urine cytology, IVP and cystoscopy in combination with adequate tissue harvest by transurethral resection are the basis of our diagnostic procedures. Bimanual palpation, systematic biopsies, sonography, computed tomography, bone scan and further procedures are not to be considered as routine examinations and are only used in special situations. Only exactly defined diagnostic algorithms permit the development and use of valid prognostic parameters. They further allow to perform a tumor-orientated therapy and to compare patient groups which have been treated in different institutions according to similar or different therapeutic regimens. This includes the importance of a TNM-oriented therapy. It has to be stressed though that the prevalence of distinct pathological changes, such as bone metastases in T1 tumors, as well as financial resources, have to be taken into account. Further, definite therapeutic intention such as a curative vs. palliative regimen is a decisive criterium for the amount of performed diagnostic procedures. It also is of importance that new diagnostic modalities, if introduced into the clinical routine, have to be investigated concerning their validity in relevant and large patient cohorts and their rationale in our diagnostic algorithm has to be defined. This is predominantly not the case in radiological imaging techniques and thus a large amount of resources are wasted.

Algorithms↗

[Bone scintigraphy and rhenium radioisotope management in the course of metastatic prostatic cancer].

A 78-year-old patient with prostate cancer and osseous metastases had a pain symptomatic. In the Urology he was treated with antiandrogenes. The outcome of the bone scintigraphy showed a super bone scan with normalization after antiandrogene-therapy which seemed to be a sign of remission, before he showed a progressive form with multiple osseous metastases. Pain could not be treated with non steroidal antiphlogistics and opiates, so the indication for treatment with Rhenium-186-HEDP was given in this case.

Aged↗

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↗

Use of Lewis X antigen and deoxyribonucleic acid image cytometry to increase sensitivity of urinary cytology in transitional cell carcinoma of the bladder.

PURPOSE: To improve sensitivity and specificity of urinary cytology for bladder cancer cell detection we used deoxyribonucleic acid (DNA) image cytometry and the monoclonal anti-Lewis X antibody P12. MATERIALS AND METHODS: Spontaneously voided urine and additional barbotage bladder washings of 25 patients with transitional cell carcinomas and 25 patients with benign diseases of the bladder were analyzed by conventional cytology, immunocytology and DNA image cytometry. The DNA content was determined in specimens stained with Feulgen according to the European Society for Analytical Cellular Pathology consensus report on standardization of DNA image cytometry. For the immunocytological examination we used the avidin-biotin-complex immunoperoxidase method with the monoclonal antibody P12 directed against the Lewis X determinant. RESULTS: The cytological examination revealed a sensitivity of 72% and a specificity of 100%. By using DNA image cytometry with Kolmogoroff-Smirnow test sensitivity increased up to 84% with a specificity of 100%. The immunocytological examination with Lewis X showed a sensitivity of 84% and a specificity of 80%. CONCLUSIONS: Combining cytology and DNA cytometry the overall sensitivity increased to 92% and with the additional application of immunocytology for Lewis X antigen sensitivity it increased to 96% but was accompanied by a decrease in specificity to 80%. DNA image cytometry and Lewis X antigen detection are not suitable for screening but suspicious urothelial cells in urinary cytology specimens can be evaluated specifically by DNA measurements. In the future it needs to be clarified whether DNA image cytometry in combination with Lewis X antigen detection can help to signal relapse and progression of transitional cell carcinoma of the bladder.

Aged↗

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↗

Gadolinium-enhanced excretory MR urography after low-dose diuretic injection: comparison with conventional excretory urography.

PURPOSE: To evaluate the clinical utility and morphologic accuracy of gadolinium-enhanced excretory magnetic resonance (MR) urography after low-dose diuretic injection and to correlate the results with those of conventional urography. MATERIALS AND METHODS: In 71 patients with urologic symptoms, excretory MR urography was performed after intravenous injection of 5-10 mg furosemide and, 30-60 seconds later, 0.1 mmol of gadopentetate dimeglumine per kilogram of body weight. The MR urograms were interpreted by three radiologists, who were blinded to the clinical outcome, and subsequently compared with conventional urograms. RESULTS: Injection of furosemide before contrast material led to rapid, uniform gadolinium distribution inside a sufficiently distended collecting system such that there was no excessive concentration of gadolinium in the urine. In patients with normal or moderately reduced excretory function, this effect allowed complete visualization of the urinary tract within 5-20 minutes of contrast material injection while minimizing gadolinium-related endoluminal T2* effects. The clinical course helped verify almost all MR urographic results. The MR urographic technique was significantly superior to conventional urography in the assessment of the ureters and bladder (P < .0001). Delineation of small caliceal abnormalities is still problematic. The best depiction of the pelvicaliceal system was obtained with fat-suppressed MR imaging, although it was still slightly inferior to conventional urography (P < .05). CONCLUSION: Gadolinium-enhanced excretory MR urography performed after low-dose diuretic injection is a promising and accurate alternative to conventional excretory urography for imaging the morphology of the urinary tract.

Adult↗

Is prostate-specific antigen a reliable marker of bone metastasis in patients with newly diagnosed cancer of the prostate?

OBJECTIVE: Staging in patients with newly diagnosed cancer of the prostate has significant ramifications in the management of the disease. At present, measurement of serum prostate-specific antigen (PSA) concentration and radionuclide bone scintigraphy are two important procedures in the metastatic work-up of these patients. We evaluated the efficacy of PSA as a staging marker to discriminate prostate cancer patients with and without bone metastases. METHODS: In a retrospective study, 359 prostate cancer patients with (n = 40) and without (n = 319) bone metastases were analyzed. In all patients the initial PSA measurement as well as the radionuclide bone scan were evaluated. RESULTS: Patients without bone metastases demonstrated a median serum PSA concentration of 12 ng/ml, whereas those with bone metastases revealed a median serum PSA concentration of 59 ng/ml, with 7 patients demonstrating a serum PSA concentration of < 10 ng/ml. This resulted in a negative predictive value of 96%. In addition, only 40% of these patients with bone metastases demonstrated a serum PSA concentration of > 100 ng/ml, which resulted in a positive predictive value of 50%. CONCLUSION: The serum PSA concentration seems only to provide limited information with regard to the presence of bone metastasis in patients with newly diagnosed cancer of the prostate. We therefore question whether a staging radionuclide bone scan may be omitted in patients with a serum PSA value of < 10 ng/ml.

Adenocarcinoma↗

Involvement of the urogenital tract in patients with five or more separate malignant neoplasms. Case and review.

Occurrence of metachronous primary malignant neoplasms (PMN) in five or more different organs and tissue of the same patient is a very rare event. The present paper reports on a female patient who experienced Hodgkin's disease of nodular sclerotic type (stage IV), carcinoma of the cervix uteri (stage I), adenocarcinoma of the rectum (Dukes A), and a well-differentiated adenocarcinoma of the stomach (pT1) before she demonstrated multicentric transitional cell carcinoma of the renal pelvis and ureter (pT3b G2-3) and of the bladder (pTa G2). Although an increased inherent predisposition of the patient to exhibit those neoplasms, similar to Lynch syndrome II, is to be discussed, her previous treatments with cyclophosphamide and external radiotherapy are likely to explain at least the occurrence of urothelial cancer. However, a report on renal pelvis and ureteral cancer induced by cyclophosphamide or irradiation is a rarity in itself.

Adenocarcinoma↗

Cytokeratin 8/18 levels in patients with prostate cancer and benign prostatic hyperplasia.

OBJECTIVES: Recently, tissue polypeptide-specific antigen (TPS), a cytokeratin 18 marker, was described to be discriminative between cancer of the prostate (CaP) and benign prostatic hyperplasia (BPH). Cyfra 8/18, a marker which recognizes both cytokeratin 8 and 18 fragments, is discussed to improve sensitivity and specificity of TPS. We investigated whether Cyfra 8/18 serum concentration discriminates between patients with clinically localized CaP and BPH. METHODS: Serum Cyfra 8/18 levels were determined in patients with untreated CaP before radical prostatectomy (pT1-3pNoMo; n = 11) and with histologically confirmed BPH (n = 22). Cyfra 8/18 concentration was correlated to the prostate-specific antigen (PSA) concentration. RESULTS: Median Cyfra 8/18 level was 0.64 ng/ml in CaP patients and 0.57 ng/ml in BPH patients. This difference is statistically not significant (p = 0.91). Furthermore, no correlation to PSA levels could be established (CaP: r = 0.036; BPH: r = 0.09). CONCLUSION: In contrast to a recent report we found the Cyfra 8/18 serum concentration to be a nondiscriminative parameter between CaP and BPH.

Adenocarcinoma↗

Efficacy of skeletal alkaline phosphatase and prostate-specific antigen in the diagnosis of bone metastasis in cancer of the prostate.

PURPOSE: To study the efficacy of prostate-specific antigen (PSA) and skeletal alkaline phosphatase (SAP) as staging markers in discriminating patients with cancer of the prostate (CaP) with (M+) and without bone metastases (M0). MATERIAL AND METHODS: 73 patients with untreated CaP entered the study. After staging the patients were divided into 3 groups: group I, patients with CaP and bone metastases (n = 21); group II, patients with locally advanced CaP without bone metastases (n = 26), and group III, patients with clinically localized CaP without bone metastases (n = 26). RESULTS: None of the M0 patients but 71% of the M+ patients exhibited an increased SAP. A corresponding cutoff point of 100 ng/ml for PSA showed that 19% of M0 patients and 71% of the M+ patients exhibited a value of >100 ng/ml. This resulted in a sensitivity and specificity of 71 and 100% of SAP and 71 and 81% for PSA, respectively. CONCLUSION: SAP could become a useful marker in the evaluation of patients with newly diagnosed CaP as it provides additional information concerning the skeletal status of these patients.

Adult↗