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Article: Amphicrine tumor.

Mándoky, L

1999 Volume 5, Issue 3, Page(s) 239–244

Abstract: The term amphicrine refers to cells, and tumors, which show both exocrine and endocrine features. Author s aim was to analyse the characteristics of these neoplasms. 40 suspicious cases were reviewed. Mucin-stains (PAS, diastase-PAS, Stains-all, Alcian- ... ...

Abstract	The term amphicrine refers to cells, and tumors, which show both exocrine and endocrine features. Author s aim was to analyse the characteristics of these neoplasms. 40 suspicious cases were reviewed. Mucin-stains (PAS, diastase-PAS, Stains-all, Alcian-blue), immunohistochemistry (antibodies against Neuron-Specific Enolase (NSE), and Chromogranin A (CGA), and electronmicroscopic studies were performed to demonstrate exocrine and/or endocrine features of the tumor cells. By means of these methods, 16 cases turned out to be amphicrine tumors. Among them, there were 4 sinonasal, 1 bronchial, 1 mediastinal, 8 gastrointestinal and 2 suprarenal gland neoplasms. In connection to the subject, a brief review is given of amphicrine tumor, regarding its etiological and pathological aspects. These tumors form a distinct clinicopathological entity and should be separated from both neuroendocrine tumors and adenocarcinomas.
MeSH term(s)	Adenocarcinoma/diagnosis ; Adenocarcinoma/pathology ; Adenocarcinoma/ultrastructure ; Adrenal Gland Neoplasms/diagnosis ; Adrenal Gland Neoplasms/pathology ; Adrenal Gland Neoplasms/ultrastructure ; Adult ; Aged ; Bronchial Neoplasms/pathology ; Bronchial Neoplasms/ultrastructure ; Carcinoid Tumor/diagnosis ; Carcinoid Tumor/pathology ; Carcinoid Tumor/ultrastructure ; Female ; Gastrointestinal Neoplasms/pathology ; Gastrointestinal Neoplasms/ultrastructure ; Humans ; Kidney Neoplasms/pathology ; Kidney Neoplasms/ultrastructure ; Male ; Mediastinal Neoplasms/pathology ; Mediastinal Neoplasms/ultrastructure ; Microscopy, Electron ; Middle Aged ; Mucins/analysis ; Neoplasms, Complex and Mixed/diagnosis ; Neoplasms, Complex and Mixed/pathology ; Neoplasms, Complex and Mixed/ultrastructure ; Paranasal Sinus Neoplasms/pathology ; Paranasal Sinus Neoplasms/ultrastructure
Chemical Substances	Mucins
Language	English
Publishing date	1999
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	1375979-6
ISSN	1532-2807 ; 1219-4956
ISSN (online)	1532-2807
ISSN	1219-4956
DOI	10.1053/paor.1999.0211
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Zs.A 4936: Show issues

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Article: Investigation of HER2 overexpression in non-small cell lung cancer.

Ugocsai, Katalin / Mándoky, László / Tiszlavicz, László / Molnár, Joseph

Anticancer research

2005 Volume 25, Issue 4, Page(s) 3061–3066

Abstract: Lung cancer is the leading cause of mortality worldwide. The median survival of advanced disease is in the range of 8 to 10 months. Intrinsic or acquired drug resistance pose major challenges to the success of chemotherapy. The HER2 gene, also known as c- ...

Abstract	Lung cancer is the leading cause of mortality worldwide. The median survival of advanced disease is in the range of 8 to 10 months. Intrinsic or acquired drug resistance pose major challenges to the success of chemotherapy. The HER2 gene, also known as c-erbB-2 or neu, is a proto-oncogene that encodes a membrane-bound receptor tyrosine kinase of the epithelial growth factor receptor (EGFR) family. It has a possible role in tumor cell proliferation, tumor invasion, tumor metastasis and drug resistance. We retrospectively investigated 88 samples of non-small cell lung cancer (NSCLC) and assessed the correlation between HER2 expression and tumor histology. The expression of HER2 protein was analyzed by immunohistochemical staining (IHC) and HER2 DNA amplification was detected by using fluorescence in situ hybridization (FISH). HER2 overexpression (2+, 3+) was detected in 5 (5.7%) out of 88 specimens. All of the HER2-overexpressing tumors histologically proved to be squamous cell carcinoma (SCC). Cases with 2+ HER2 immunoreactivity showed either no amplification (3.875 and 2.525), or borderline amplification (4.75). Cases with 3+ HER2 immunoreactivity showed moderate amplification (7.35) and strong amplification (15-20 - cluster), respectively. The HER2 expression in NSCLC was relatively low in the selected Hungarian population; consequently, there is no indication for introduction of trastuzumab for the treatment of lung cancer.
MeSH term(s)	Adult ; Aged ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/metabolism ; Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/therapy ; Combined Modality Therapy ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Lung Neoplasms/therapy ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/biosynthesis ; Receptor, ErbB-2/genetics ; Retrospective Studies
Chemical Substances	Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2005-07
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
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Article: Az ún. "szürke zóna" az emlobetegségek vékonytu aspirációs citológiájában.

Bak, Mihály / Szabó, Eva / Mándoky, László

Magyar sebeszet

2005 Volume 58, Issue 1, Page(s) 3–7

Abstract: Fine needle aspiration cytology (FNAC) is an essential procedure in the diagnosis of premalignant and malignant lesions of the breast. A "gray zone" exists between benign and malignant lesions in FNAC of breast; there an unequivocal diagnosis cannot be ... ...

Title translation	The "gray zone" in fine needle aspiration cytology of the breast.
Abstract	Fine needle aspiration cytology (FNAC) is an essential procedure in the diagnosis of premalignant and malignant lesions of the breast. A "gray zone" exists between benign and malignant lesions in FNAC of breast; there an unequivocal diagnosis cannot be reached. Lesions in "gray zone" are categorized as "probably benign with atypia" (C3) and "probably malignant" (C4). Authors compared the cytology with histopathology and clinical follow-up of "gray zone" breast lesions, classified either as C3 or as C4 by FNAC. Amongst the total of 1679 FNACs, 85 (5%) were diagnosed as C3, whereas 101 (6%) were diagnosed as C4. Of the C3 cases, 48 patients underwent surgical biopsy. Histology proved malignancy in 21 (44%) cases, and was benign in 27 (56%) cases. Eighty-five open biopsies were performed out of the C4 cases. The histology was malignant in 76 (89%) cases, and benign in 9 (11%) cases. Lesions belong to "gray zone" should be taken into consideration in the FNAC of the breast and patients must be informed regarding this fact.
MeSH term(s)	Biopsy, Fine-Needle ; Breast Diseases/pathology ; Breast Neoplasms/pathology ; Diagnosis, Differential ; Female ; Humans
Language	Hungarian
Publishing date	2005-02
Publishing country	Hungary
Document type	Comparative Study ; English Abstract ; Journal Article
ZDB-ID	414068-0
ISSN	0025-0295
ISSN	0025-0295
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Zs.A 5702: Show issues

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Article: Reversal of multidrug resistance of cancer cells in vitro: modification of drug resistance by selected carotenoids.

Gyémánt, Nóra / Tanaka, Masaru / Molnár, Péter / Deli, József / Mándoky, László / Molnár, Joseph

Anticancer research

2006 Volume 26, Issue 1A, Page(s) 367–374

Abstract: The development of multidrug resistance (MDR) causes difficulties in the chemotherapy of of human cancer. Investigation of the possibility of reversal of MDR has been greatly aided by the use of cell lines with acquired resitance to anticancer agents in ... ...

Abstract	The development of multidrug resistance (MDR) causes difficulties in the chemotherapy of of human cancer. Investigation of the possibility of reversal of MDR has been greatly aided by the use of cell lines with acquired resitance to anticancer agents in vitro or transfected with the mdrl gene. The aim of this study was to examine new perspectives of chemotherapy focused on natural, carotenoid compounds, in connection with the modification of MDR. The function of the MDR protein was examined via the R123 drug accumulation of both cell lines in the presence of carotenoids. The fluorescence of the cell population was measured by flow cytometry. The most effective resistance modifiers Monoepoxy-beta-carotene, (SS, 8S)-capsochrome, (8'S) Luteoxanthin, (9Z)-Violaxanthin, (9Z)-Zeaxanthin, (13Z)-Zeaxanthin were assayed for their antiproliferative effects in combination with the anti-cancer drug epirubicin. (13Z)-Zeaxanthin was able to enhance the antiproliferative effect on human mdrl gene transfected mouse lymphoma and anthracycline resistant human breast cancer cell line MCF7. (8'S)-luteoxanthin, (5S, 8S)-capsochrome and (9Z)-zeaxanthin treatment revealed synergism with epirubicin on resistant mouse lymphoma. The enhanced antiproliferative activity of epirubicin combinated with (9Z)-Violaxanthin was more significant on MCF7 cells resistant to anthracycline.
MeSH term(s)	ATP-Binding Cassette, Sub-Family B, Member 1/biosynthesis ; ATP-Binding Cassette, Sub-Family B, Member 1/genetics ; ATP-Binding Cassette, Sub-Family B, Member 1/metabolism ; Animals ; Carotenoids/pharmacology ; Doxorubicin/pharmacology ; Drug Resistance, Multiple/drug effects ; Drug Resistance, Neoplasm ; Drug Synergism ; Leukemia L5178/drug therapy ; Leukemia L5178/metabolism ; Mice ; Stereoisomerism ; Structure-Activity Relationship ; Verapamil/pharmacology
Chemical Substances	ATP-Binding Cassette, Sub-Family B, Member 1 ; Carotenoids (36-88-4) ; Doxorubicin (80168379AG) ; Verapamil (CJ0O37KU29)
Language	English
Publishing date	2006-01
Publishing country	Greece
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
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Article: In vitro search for synergy between flavonoids and epirubicin on multidrug-resistant cancer cells.

Gyémánt, N / Tanaka, M / Antus, S / Hohmann, J / Csuka, O / Mándoky, L / Molnár, J

In vivo (Athens, Greece)

2005 Volume 19, Issue 2, Page(s) 367–374

Abstract: The drug accumulation of a human multidrug resistance 1 (mdr1) gene-transfected mouse lymphoma cell line and a multidrug resistance protein (MRP)-expressing human breast cancer cell line MDA-MB-231 was compared in the presence of sixteen flavonoids and ... ...

Abstract	The drug accumulation of a human multidrug resistance 1 (mdr1) gene-transfected mouse lymphoma cell line and a multidrug resistance protein (MRP)-expressing human breast cancer cell line MDA-MB-231 was compared in the presence of sixteen flavonoids and five isoflavonoids. The expression of the 170-kDa P-glycoprotein (P-gp) (MDR1) and 190-kDa multidrug resistance protein (MRP) in both cell lines was confirmed by immunocytochemistry. The rhodamine 123 accumulation of the P-glycoprotein (P-gp)-expressing cells increased up to 46.4, while 2,7'-bis(2-carboxyethyl)-5(6)-carboxy-fluorescein acetoxymethyl ester (BCECF-AM) accumulation of the MRP-expressing cells increased up to 1.6, in fluorescence activity ratio (FAR). Major P-gp-mediated efflux pump modifiers are formononetin, amorphigenin, rotenone and chrysin, while MRP-mediated efflux pump modifiers are formononetin, afrormosin, robinin, kaempferol and epigallocatechin. In antiproliferative assay, afrormosin, amorphigenin, chrysin and rotenone exhibited the strongest antiproliferative effects in L5178 (max. ID50: 19.70) and MDA-MB-231 cell lines (max. ID50: 55.47). In a checkerboard microplate method in vitro, furthermore, the most effective multidrug resistance (MDR) resistance modifiers, amorphigenin, formononetin, rotenone and chrysin, were assayed for their antiproliferative effects in combination with epirubicin. Rotenone and afrormosin showed additive effects. Chrysin and amorphigenin on the mouse lymphoma cell line and formononetin on the MDA-MB-231 cell line synergistically enhanced the effect of epirubicin.
MeSH term(s)	ATP Binding Cassette Transporter, Sub-Family B/metabolism ; Animals ; Antineoplastic Agents/pharmacology ; Cell Proliferation/drug effects ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Drug Synergism ; Epirubicin/pharmacology ; Flavonoids/pharmacology ; Humans ; Isoflavones/pharmacology ; Mice ; Structure-Activity Relationship ; Tumor Cells, Cultured
Chemical Substances	ATP Binding Cassette Transporter, Sub-Family B ; Antineoplastic Agents ; Flavonoids ; Isoflavones ; Epirubicin (3Z8479ZZ5X)
Language	English
Publishing date	2005-03
Publishing country	Greece
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
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Zs.A 2288: Show issues

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

Olasz, Judit / Mándoky, László / Géczi, Lajos / Bodrogi, István / Csuka, Orsolya / Bak, Mihály

Anticancer research

2005 Volume 25, Issue 6B, Page(s) 4319–4324

Abstract: 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 ...

Abstract	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.
MeSH term(s)	Adaptor Proteins, Signal Transducing ; Adolescent ; Adult ; Antineoplastic Agents/pharmacology ; Base Pair Mismatch ; Carrier Proteins/biosynthesis ; Carrier Proteins/genetics ; Cisplatin/pharmacology ; DNA Methylation ; DNA Repair/physiology ; DNA-Binding Proteins/biosynthesis ; DNA-Binding Proteins/deficiency ; DNA-Binding Proteins/genetics ; Drug Resistance, Neoplasm ; Humans ; Male ; Microsatellite Repeats/genetics ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein/biosynthesis ; MutS Homolog 2 Protein/deficiency ; MutS Homolog 2 Protein/genetics ; Neoplasm Staging ; Neoplasms, Germ Cell and Embryonal/drug therapy ; Neoplasms, Germ Cell and Embryonal/genetics ; Nuclear Proteins/biosynthesis ; Nuclear Proteins/deficiency ; Nuclear Proteins/genetics ; Testicular Neoplasms/drug therapy ; Testicular Neoplasms/genetics
Chemical Substances	Adaptor Proteins, Signal Transducing ; Antineoplastic Agents ; Carrier Proteins ; DNA-Binding Proteins ; G-T mismatch-binding protein ; MLH1 protein, human ; Nuclear Proteins ; MSH2 protein, human (EC 3.6.1.3) ; MutL Protein Homolog 1 (EC 3.6.1.3) ; MutS Homolog 2 Protein (EC 3.6.1.3) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2005-11
Publishing country	Greece
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
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Article: Clinical relevance of HER-2/neu expression in germ-cell testicular tumors.

Mándoky, László / Géczi, Lajos / Bodrogi, István / Tóth, József / Csuka, Orsolya / Kásler, Miklós / Bak, Mihály

Anticancer research

2004 Volume 24, Issue 4, Page(s) 2219–2224

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Adult ; Choriocarcinoma/genetics ; Choriocarcinoma/metabolism ; Choriocarcinoma/pathology ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Neoplasm Staging ; Receptor, ErbB-2/biosynthesis ; Receptor, ErbB-2/genetics ; Teratoma/genetics ; Teratoma/metabolism ; Teratoma/pathology ; Testicular Neoplasms/genetics ; Testicular Neoplasms/metabolism ; Testicular Neoplasms/pathology
Chemical Substances	Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2004-07
Publishing country	Greece
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
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Article: Expression and prognostic value of the lung resistance-related protein (LRP) in germ cell testicular tumors.

Mándoky, László / Géczi, Lajos / Doleschall, Zoltán / Bodrogi, István / Csuka, Orsolya / Kásler, Miklós / Bak, Mihály

Anticancer research

2004 Volume 24, Issue 2C, Page(s) 1097–1104

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Adolescent ; Adult ; Blotting, Western ; Germinoma/genetics ; Germinoma/metabolism ; Germinoma/pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Proteins/biosynthesis ; Neoplasm Proteins/genetics ; Neoplasm Staging ; Prognosis ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Testicular Neoplasms/genetics ; Testicular Neoplasms/metabolism ; Testicular Neoplasms/pathology ; Vault Ribonucleoprotein Particles/biosynthesis ; Vault Ribonucleoprotein Particles/genetics
Chemical Substances	Neoplasm Proteins ; RNA, Messenger ; Vault Ribonucleoprotein Particles ; major vault protein
Language	English
Publishing date	2004-03
Publishing country	Greece
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
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Article: A lung rezisztencia protein (LRP) expressziójának vizsgálata hererákokban.

Mándoky, László / Géczi, Lajos / Doleschall, Zoltán / Csuka, Orsolya / Bodrogi, István / Bak, Mihály

Magyar onkologia

2002 Volume 46, Issue 4, Page(s) 339–345

Abstract: 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 ... ...

Title translation	Lung resistance protein analysis in testicular cancer.
Abstract	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.
MeSH term(s)	Adult ; Aged ; Biomarkers, Tumor/analysis ; Blotting, Western ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic ; Germinoma/chemistry ; Germinoma/drug therapy ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Proteins/analysis ; Neoplasm Proteins/genetics ; RNA, Messenger/analysis ; Reverse Transcriptase Polymerase Chain Reaction ; Testicular Neoplasms/chemistry ; Testicular Neoplasms/drug therapy ; Vault Ribonucleoprotein Particles/genetics
Chemical Substances	Biomarkers, Tumor ; Neoplasm Proteins ; RNA, Messenger ; Vault Ribonucleoprotein Particles ; major vault protein
Language	Hungarian
Publishing date	2002
Publishing country	Hungary
Document type	English Abstract ; Journal Article
ZDB-ID	414033-3
ISSN	0025-0244
ISSN	0025-0244
DOI	HUON.2002.46.4.0339
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Article: Apoptosis regulation and spontaneous apoptosis index of testicular germ cell tumors are associated with differentiation and resistance to systemic treatment.

Mandoky, László / Szende, Béla / Géczi, Lajos / Bodrogi, István / Kásler, Miklós / Bak, Mihály

Anticancer research

2008 Volume 28, Issue 3A, Page(s) 1641–1649

Abstract: Background: Cisplatin-based chemotherapy can cure more than 80% of metastatic germ cell testicular tumors (GCT). Germ cells are particularly susceptible to apoptosis and it is reasonable to presume that GCTs are curable because of an intact and ... ...

Abstract	Background: Cisplatin-based chemotherapy can cure more than 80% of metastatic germ cell testicular tumors (GCT). Germ cells are particularly susceptible to apoptosis and it is reasonable to presume that GCTs are curable because of an intact and effective apoptotic pathway. Patients and methods: The expression of p53 and p21 was investigated in conjunction with the spontaneous apoptotic index in 20 refractory and 50 chemosensitive GCTs, with a complete follow-up. To detect a differentiation-dependent alteration in the apoptotic pathway, all of the histological tumor types were examined separately. Results: Embryonal carcinoma components showed significantly higher p53 expression compared to other histological subtypes of GCTs. p21 was barely detectable in the majority of tumors. Seminomatous components showed no p21 expression. Mature teratomas and syncytiotrophoblasts showed significantly higher p21 expression than other tumor subtypes. Embryonal carcinomas showed significantly higher apoptotic indices than other non-seminomatous components. On the other hand, choriocarcinomas and mature teratomas showed the lowest spontaneous apoptotic potential. The apoptotic index correlated with the fraction of p53-positive cells, but not with the p21 expression rate. The refractory group showed significantly lower p53 expression, higher p21 expression and a higher apoptosis index than the sensitive group. Conclusion: Our results suggest that the p53 and p21 expression levels and the apoptosis index seem to be important factors in the issue of the chemosensitivity of GCTs. The protein expression pattern reflects a differentiation-dependent preference for G1/S-phase arrest in terminally differentiated syncytiotrophoblasts and mature teratoma cells, while p53 mediated apoptosis induction is meaning to less differentiated tumor types.
MeSH term(s)	Adolescent ; Adult ; Apoptosis/physiology ; Cell Differentiation/physiology ; Cyclin-Dependent Kinase Inhibitor p21/biosynthesis ; Cyclin-Dependent Kinase Inhibitor p21/genetics ; Drug Resistance, Neoplasm ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasms, Germ Cell and Embryonal/drug therapy ; Neoplasms, Germ Cell and Embryonal/genetics ; Neoplasms, Germ Cell and Embryonal/metabolism ; Neoplasms, Germ Cell and Embryonal/pathology ; Testicular Neoplasms/drug therapy ; Testicular Neoplasms/genetics ; Testicular Neoplasms/metabolism ; Testicular Neoplasms/pathology ; Tumor Suppressor Protein p53/biosynthesis ; Tumor Suppressor Protein p53/genetics
Chemical Substances	CDKN1A protein, human ; Cyclin-Dependent Kinase Inhibitor p21 ; TP53 protein, human ; Tumor Suppressor Protein p53
Language	English
Publishing date	2008-05
Publishing country	Greece
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
Database	MEDical Literature Analysis and Retrieval System OnLINE

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