Biomedical subjects

István Bodrogi

Publications and source records attributed to István Bodrogi.

14 recordsLinked to original sources

PubMed2007

[Molecular pathology and targeted therapy of clear cell renal cancer].

The golden standard of care for advanced renal cell cancer (RCC) was until now the cytokine therapy with relatively low response rates. Advances of molecular genetics in RCC revealed several molecular targets such as VHL and angiogenic genotype or EGFR in the clear cell variant. Among the novel targeted agents, multiple tyrosine kinase inhibitors were proved to be clinically effective against advanced clear cell renal cancer, changing the standard of care. It is a further question how molecular diagnostics can improve these results by the detection of these targets or gene defects in individual tumors.

Adenocarcinoma, Clear Cell↗

PubMed2007

[Detection of late ototoxic side effect of cisplatin by distortion otoacoustic emission (DPOAE)].

Cisplatin-based chemotherapy results in high cure rate in testicular cancer. The issue of toxicity is of special concern in young men with a probability of cure of at least 70-80% even in disseminated disease. As the literature shows, the ototoxic side effects of cisplatin have been studied mostly by conventional method. The authors used distortion product otoacoustic emission to detect the long-term ototoxic effect of cisplatin in 223 patients with a median follow-up time of 4.27 years (range 0.5-20 years) and a median age of 37 years (range 18-55 years). Cisplatin (20 mg/m(2) body surface) was administered for five days per cycle, in combination with other antitumor drugs. The control group consisted of 40 testicular cancer patients who did not receive chemotherapy, with a median age of 35 years (range 16-54 years). A detailed medical history based on a standardized questionnaire evaluated hearing complaints and audiological risk factors, such as head injuries, chronic otitis media, previous noise exposure and familial hearing loss. DPOAE was measured at 8 frequencies from 750 to 8000 Hz. No amplitude changes were detected in patients receiving =300 mg/m(2) cisplatin. At higher doses, contrary to the literature, not only high frequencies were affected: our method could detect significant hearing impairment at lower frequencies important for speech perception in patients receiving at least 400 mg/m(2) cisplatin. The lower frequencies where significant amplitude changes were detected were 3000 Hz at 400 mg/m(2), and 1500, 2000 and 3000 Hz at 500-600 mg/m(2). We detected the worst hearing in the case of patients who had symptomatic ototoxicity. Age and the cumulative dose of cisplatin proved statistically significant risk factors, while smoking or noise exposure did not have predictive value. As a conclusion, DPOAE is a fast, noninvasive and reliable method for the detection of late ototoxicity in testicular cancer patients. In our study hearing loss correlated with the cumulative dose of cisplatin. Hearing impairment contributes to the already compromised situation of cancer patients.

Adolescent↗

PubMed2004

Increased predisposition to cancer in brothers and offspring of testicular tumor patients.

Cancer susceptibility was examined in first-degree relatives of 293 testicular tumor patients (TTPs) and 586 age-matched healthy males. Significantly increased risk was found in the families of TTPs (OR: 1.4; CI: 1.08-1.79), however, except for testicular cancer of 7 brothers (OR: 11.7; CI: 1.42-256.5), and 6 various childhood tumors (bilateral Wilms' tumor, neuroblastoma, medulloblastoma, ALL, histiocytosis-X, testicular tumor) of 200 offspring (OR: 12.9; CI: 1.54-286.2), no association with other malignancies was observed. No differences were seen between the fertility of patients and controls when occupational or socio-economic status of the families was taken into account. However, the majority of the controls (85%) fathered the first child between 20-30 years of age, while only 61% of TTPs had the first child in the same age group. TTPs fathered more girls than boys (P=0.009), and the lower male - higher female ratio of index children was also identical, irrespective of the conception taking place before or after the father's treatment. Occupations did not, but smoking might have influenced cancer susceptibility of the patients. Aggregation of fraternal testicular tumors, and both dramatically increased cancer risk and altered sex ratio of the offspring indicate a remarkable role of hereditary factors in tumorigenesis and later consequences of a certain portion of testicular malignancies, which must be refined by molecular studies.

Adolescent↗

PubMed2004

[Different histological findings in two specimens from pulmonary metastasectomy in the same patient].

INTRODUCTION: Out of the 3310 thoracic surgical procedures performed between 1980 and 2000 at the Department of Surgery of the National Institute of Oncology in Budapest, 258 were pulmonary metastasectomies involving 236 patients. Primary tumors were the following in order of decreasing frequency: testicular cancer, colorectal cancer, renal cancer, soft tissue tumor, breast cancer and others. METHODS: In the present study the authors report two patients with multiple pulmonary metastases. The primary tumor was non-seminoma testicular cancer in case one and endometrial cancer in case two (previously treated for thyroid cancer). Histological examination of resected specimens revealed unsuspected focal inactive tuberculosis in the first case and medullary thyroid cancer in the second. CONCLUSIONS: In the reported two cases the following conditions of metastasectomy were given: 1. satisfactory cardiopulmonary status, 2. possibility of surgical radicality, 3. locoregional disease control, 4. prior chemotherapy in chemosensitive tumor (case one). The generally accepted condition of metastasectomy-lack of clinically manifest disease in other distant organs--was not fulfilled in case two (suspected liver metastases).

Adult↗

PubMed2004

Topoisomerase-II alpha expression as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel.

PURPOSE: The predictive value of topoisomerase-II alpha (topo-II) has been evaluated in advanced breast cancer patients randomly treated with single-agent doxorubicin or docetaxel. EXPERIMENTAL DESIGN: Primary tumor samples from patients enrolled in a randomized, phase III clinical trial comparing single-agent doxorubicin (75 mg/m(2) q3wks) with docetaxel (100 mg/m(2) q3wks) were collected and topo-II status was evaluated by immunohistochemistry (clone KiS1). RESULTS: Topo-II status was evaluated in 108 samples, 55 (51%) in the doxorubicin arm and 53 (49%) in the docetaxel arm. An increment of 10% in cells expressing topo-II is associated with a statistically significant odds ratio (OR; 95% confidence interval) of 1.09 (1.03-1.15; P = 0.002) for overall response to doxorubicin versus 1.002 (0.94-1.07; P = 0.95) in the docetaxel arm. With increasing topo-II, the favorable OR for overall response to docetaxel compared with doxorubicin decreases to become not significant in patients with topo-II tumor content >10%. In a multivariate analysis, (a) HER-2 status seems positively correlated with overall response to chemotherapy (OR, 2.34; 95% confidence interval, 0.87-6.27; P = 0.09). (b) Overall response to doxorubicin is significantly lower than overall response to docetaxel (OR, 0.17; 95% confidence interval, 0.04-0.64; P = 0.009) but with a significant interaction term for doxorubicin-treated patients with topo-II tumor content >10% (OR, 8.31; 95% confidence interval, 1.86-37.03; P = 0.05). CONCLUSIONS: (a) Topo-II overexpression confers a higher probability of response in the doxorubicin arm only. (b) Despite being a small retrospective study, this study is in line with previously reported studies and the hypotheses raised are now being tested in a prospective neoadjuvant trial.

Adult↗

PubMed2003

[Role of gemcitabine/cisplatin in the treatment of advanced and metastatic bladder cancer].

M-VAC combination chemotherapy was considered as the "gold standard" of the treatment of advanced and metastatic bladder cancers. Arrival of gemcitabine or taxanes in the 90s attracted attention since their efficacy was combined with low toxicity profiles. Gemcitabine/cisplatin combination became the most frequently studied treatment modality in the past 3 years. Multicentric, multinational randomized phase-III study indicated that in bladder cancer the gemcitabine/cisplatin combination is equal to M-VAC while in the case of the former the risk to benefit ratio is lower. Accordingly, gemcitabine/cisplatin combination is a safer treatment option in advanced and metastatic bladder cancer and is a real alternative to M-VAC. In the case of patients where cisplatin cannot be administered due to poor renal function, the new drugs with better toxicity profiles provide further treatment options.

Adult↗

PubMed2003

The incidence, prognosis, clinical and histological characteristics, treatment, and outcome of patients with bilateral germ cell testicular cancer in Hungary.

PURPOSE: To examine the incidence, prognosis, clinical and histological characteristics, treatment, and outcome of patients with bilateral testicular cancer in the referral center in Hungary, to determine which parameters might predict a second testicular tumor. METHODS: . Clinical parameters-such as time of original surgery, histology of primary tumor, extent of the disease, serum marker concentrations, history of testicular abnormalities, treatment, response to treatment, follow-up period, data on second carcinoma-of bilateral testicular tumors among the 2,386 patients with testicular cancer treated between November 1988 and November 1998 were analyzed. RESULTS: The incidence of patients with synchronous testicular tumor was 0.8% (19 of 2,386 patients). The clinical stages were 8 I/A, 5 I/B, 1 II/A, 2 II/B, 1 III/A, and 2 III/B. Median follow-up time was 93 months and the 5-year overall survival was 84%. The incidence of patients with metachronous testicular cancer (median age 28 years and 35 years at first and second tumor diagnosis) was 2.2% (53 of 2,386 patients) and the median time to second tumor was 76 months (range 18-203 months). The clinical stages at the first and second tumor diagnosis were: 14 I/A, 21 I/B, 15 II/A, 2 II/B, and 1 III/B, and 26 I/A, 16 I/B, 3 II/A, 1 II/B, 7 III/B, respectively. The median follow-up time was 42 months and the 5-year overall survival was 93%. In thirteen patients with metachronous cancers, two family histories of testicular cancer, five cases of undescended testicles, seven cases of testicular atrophy, and one case of azoospermia were detected. There was a non-significant trend to a longer cancer interval after chemotherapy and radiotherapy and a tendency to a greater incidence of asynchronous seminoma after chemotherapy. Clinical stage I tumors were more frequent in the surveyed group than among patients not followed up according to the institutional protocol ( P = 0.01), but the survival rate was good in both groups. Seminoma as a second tumor was diagnosed in an older age group (median 38 years, range 25-49 years) than nonseminoma (median 32 years, range 21-51 years, P < 0.045). The interval till the appearance of a metachronous testicular cancer depended on tumor histology: in seminoma cases it was longer than in nonseminoma cases (median time: 121 months versus 50 months, P = 0.002). CONCLUSIONS: The overall incidence of bilateral testicular cancer in the referral center in Hungary was 3%. We could not identify clinical factors which predicted a higher risk for metachronous testicular cancer. With regular follow-up the early diagnosis of second testicular tumors is probable; therefore education, self-examination of the remaining testicle, and long-term follow-up are important in early detection.

Adult↗

PubMed2003

[Lung resistance protein analysis in testicular cancer].

Germ cell testicular cancers are well-curable neoplasms, because total remission can be achieved in about 80% of the cases. However, 15-20% of the patients die due to drug resistance (DR). A number of mechanisms of the multidrug resistance phenotype are known, including MDR/P-glycoprotein (P-gp) and the so-called multidrug resistance associated protein (MRP). Lung Resistance Protein (LRP) is an ATP dependent membrane transporter protein associated with MDR. In our present work we studied the expression of LRP in testicular cancers. LRP expression was determined by immunohistochemistry (IH), Western blot (WB) and RT-PCR techniques. Clinical resistance was defined in accordance with the clinical oncologic rules. In 29 (41%) of 70 primary testicular tumours and in 22 (63%) of 35 cases, elevated LRP levels were established by IH and WB, respectively. In the latter 63%, the LRP mRNA levels were elevated as well. Six cases of the 15 seminomas and 23 cases of the nonseminomatous germ cell tumours (NSGCT) proved to be positive. No relationship was demonstrated between LRP expression and the stage of the disease. Despite the LRP positivity of 6 tumour samples, all of the seminomas proved sensitive. Of the 39 sensitive NSGCT, 27 cases were LRP-negative, whereas 11 tumour samples of 16 patients belonging to the resistant group proved LRP-positive (p=0.04). The authors concluded that the expression of LRP is responsible for clinical drug resistance in non-seminomatous testicular cancer patients.

Adult↗

PubMed2002

[Positron emission tomography in the investigation of malignant testicular tumors].

Thirty-three [18F]-FDG and ten [11C]-methionine (altogether 43) PET studies were performed in 37 (24 non-seminoma and 13 seminoma) patients. All results were assessed on the basis of histology (or cytology) or clinical follow-up. PET scan identified metastatic disease in 13 cases while 30 investigations resulted in a negative medical report. There were 3 false-positive cases and no false-negative results were obtained. The false-positive results were likely to occur due to FDG accumulation in benign lesions. There were no false-positive findings with the use of [11C]-methionine. Sensitivity, specificity and accuracy were 100%, 91% and 93%, respectively, using both tracers.

Adolescent↗

PubMed2000

[Early diagnosis of testicular cancer]

PURPOSE: The authors analyze their 3-year results of the "educational and early detection program for testicular cancer". The goals of the program are to reduce the duration of symptoms and to improve early detection. METHODS: Advertisements were placed in the media describing the early signs of testicular cancer, the risks factors, the correct method of self-investigation and the importance of early detection. Between 1 April, 1995 and 1 April, 1998 5056 volunteers were examined. They underwent physical and ultrasound examination of the testicles, and in case of suspicious findings, tumor markers (alpha-fetoprotein, human choriogonadotropin) were checked. RESULTS: Testicular tumors were found in 1.28% of patients with symptoms (testicular enlargement or nodules). No tumor was found in the population that was symptom-free, or in patients with pain, sensitivity to palpation, or unrelated complaints. Of the patients with a palpable lump and swollen testicles, 4.5 and 3.9% were found to have tumors respectively. In total 32 testicular tumors were detected in 30 patients: 15 (2 bilateral) seminomas, 13 non-seminomas and 4 benign tumors. The occurrence of malignant testicular tumors was most frequent, 1.6% in the age group between 15 and 40 years. The stages were as follows: 9 I/A, 9 I/B, 1 I/S, 3 II/A, 1 II/B and 2 III/B. One patient was lost to follow-up after castration. All the other patients achieved complete remission. CONCLUSION: Despite the increasing incidence of testicular cancer screening of asymptomatic men does not lead to detection of tumors. The awareness of the early signs associated with cancer, self-examination, ultrasound examination of the testicle help in establishing an early diagnosis, nevertheless a widescale program for the early detection of testicular cancer is not justifiable. Effective early detection should be based on an educational program for the population at risk, the appropriate training of doctors and staff engaged in the health care of the young, and the initiation and facilitation of early ultrasound examination at the first symptoms. Serum markers play a limited role in early diagnosis.

Journal Article↗

PubMed1995

DNA Ploidy Pattern in Pure Seminomas.

Nuclear extract and image cytometry was used to determine the DNA ploidy pattern of 31 pure seminomas. At least 5-year but usually 10-year follow-up was available to compare the clinical outcome to the DNA ploidy pattern. In 24 cases (77.4%) the DNA indexes (DI) showed tetraploid (1,8 < DI < 2,2) pattern confirming the recent cytogenetic and flow cytometric DNA studies of others. However, in 7 cases (22,6%) the tumors were aneuploid. Out of these aneuploid cases 2 had two subpopulations and 2 had less than 1,8 DI. These latter cases (providing the loss of chromosomal DNA) had elevated AFP levels in serum that raises the question of nonseminomatous transformation without any morphological evidence. Usually, the aneuploid cases had worse prognoses but there was no significant difference. Because of the small number of aneuploid cases wider clinicopathologic studies are required to confirm our results.

Journal Article↗

PubMedDate not supplied

Expression and prognostic value of the lung resistance-related protein (LRP) in germ cell testicular tumors.

BACKGROUND: Lung resistance-related protein (LRP) was first detected in a non-P-glycoprotein-mediated multidrug-resistant lung cancer cell line and has been shown to be the major human vault protein. The aim of this study was to evaluate the expression of LRP in germ cell testicular tumors (GCT) and to determine the correlation between LRP expression and the clinical outcome of these tumors. PATIENTS AND METHODS: Seventy cases of primary testicular tumors were investigated. LRP protein was detected by immunohistochemistry and Western blotting methods. LRP mRNA was determined with RT-PCR. Patients' clinical parameters and tumor response to treatment were recorded. RESULTS: With immunohistochemistry, LRP was detected in 29 (41%) out of 70 primary testicular tumors. Twenty-two (63%) out of 35 tumors expressed LRP mRNA and LRP protein on examination by RT-PCR and Western blotting, respectively. Pure teratomas showed significantly higher LRP expression compared to other types of GCTs (p=0.0418). No relationship was demonstrated between the LRP immunostaining and stage of disease (p=0.2263). A significantly higher proportion of patients with LRP-negative tumors achieved complete response than those with LRP-positive tumors (p=0.0155). Patients whose tumors showed expression of LRP had significantly shorter overall survival (p=0.0428) than LRP-negative patients. CONCLUSION: Immunohistochemistry is a reliable method to evaluate LRP expression in testicular germ cell tumors. A positive correlation was found between LRP immunostaining and pure teratomas. LRP expression was associated with an adverse clinical outcome and shorter overall survival. Our findings suggest that LRP has prognostic value in testicular germ cell tumors and can predict clinical outcome.

Adolescent↗

PubMedDate not supplied

Clinical relevance of HER-2/neu expression in germ-cell testicular tumors.

BACKGROUND: Amplification and/or overexpression of HER-2/neu are associated with poor clinical outcome in several epithelial tumors. However, the exact prognostic role of HER-2/neu expression in testicular germ-cell tumors is equivocal. PATIENTS AND METHODS: Since teratomas are relatively chemoresistant tumors, we evaluated the HER-2/neu alterations of 59 primary testicular teratomas and mixed germ-cell tumors containing teratomatous components using the standardized immunohistochemical method (IHC) (HercepTest) and Fluorescence in Situ Hybridization (FISH). RESULTS: HER-2/neu overexpression was detected in 14 (24%) out of 59 specimens. With IHC, teratomatous and choriocarcinoma components showed significantly higher HER-2/neu expression compared to other histological subtypes of GCTs (p=0.0095). A statistically significant correlation (p=0.0004) can be established between HER-2/neu status and clinical stage of the disease. Similarly, a significant correlation was observed between HER-2/neu overexpression and clinical outcome (p=0.0077). None of the specimens had definite HER-2/neu gene amplification. CONCLUSION: Our results suggest that HER-2/neu overexpression is associated with an adverse clinical outcome and has a prognostic role in testicular germ-cell tumors. Further studies are needed to evaluate the exact background of HER-2/neu overexpression in germ-cell tumors and the role of anti-HER-2/neu antibodies in the treatment regimens for this malignancy.

Adult↗

PubMedDate not supplied

Influence of hMLH1 methylation, mismatch repair deficiency and microsatellite instability on chemoresistance of testicular germ-cell tumors.

BACKGROUND: Cisplatin-based chemotherapy can cure more than 80% of metastatic germ-cell testicular tumors (GCTs). The response to cisplatin-based chemotherapy has been related to Microsatellite Instability (MSI), which is caused by genetic or epigenetic changes in genes of the DNA Mismatch Repair (MMR) pathway. PATIENTS AND METHODS: We investigated 15 refractory and 36 chemosensitive GCTs for immunohistochemical loss of hMLH1, hMSH2 and hMSH6 protein expressions, in conjunction with hMLH1 gene methylation and MSI of GCTs, with a complete follow-up. RESULTS: A loss of either of the MMR protein expressions was detected in 14 cases (27.5%). Pathological hMLH1 protein expression was seen in 10 cases (19.6%). hMLH1 methylation was found in 11 cases (21.60%) and was highly correlated with loss of hMLH1 expression (p < 0.0001) and with immunohistochemically-detected MMR deficiency (p = 0.0005). MSI was found in 16 cases (31.4%). There was no correlation between hMLH1 methylation and MSI. Neither hMLH1 methylation status, nor MSI correlated with any of the clinicopathological parameters investigated (tumor stage, histology, resistance to systemic treatment). CONCLUSION: hMLH1 gene methylation was detected as a common alteration in GCTs, and correlated with the loss of hMLH1 protein expression (p < 0.0001). Neither hMLH1 gene methylation, MMR deficiency, nor MSI showed a relationship with the relevant clinicopathological parameters.

Adaptor Proteins, Signal Transducing↗