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József Tóth

Publications and source records attributed to József Tóth.

15 recordsLinked to original sources
PubMed2006

HER-2/neu genotype of breast cancer may change in bone metastasis.

The genotype of breast cancer (BRC) is considered to be relatively stable during tumor progression, accordingly, determination of the estrogen receptor and HER-2/neu status is currently based on the primary tumor. However, recent data suggest that the gene expression profile of the metastatic lesion can be different compared to that of the primary BRC. Accordingly, it is possible that the HER-2/neu status is different in the metastatic lesion and the primary BRC. Since the bone is the most frequent metastatic site during the progression of BRC, we have analyzed the HER-2/neu status of 48 bone metastatic BRC cases by immunohistochemistry and fluorescent in situ hybridization, and it was possible to compare it to the primary site in 23 cases. The frequency of HER-2/neu amplification of BRC in the primary tumors was found to be 17.4% compared to 10.5% in bone metastases. Half of BRC cases with HER-2/neu amplification lost this genotype in bone metastases (4/23 versus 2/23, respectively) and even in the 2 cases where HER-2/neu amplification was retained in the metastases, the copy number was found to be decreased compared to the primary tumor. Based on our data and previous reports in the literature, we suggest to perform HER-2/neu testing both on primary tumor and samples obtained from BRC metastases, at least in case of primary tumors with HER-2/neu amplification, before introduction of HER-2/neu-targeting therapy.

Bone Neoplasms↗
PubMed2005

Tumor-infiltrating B cell immunoglobulin variable region gene usage in invasive ductal breast carcinoma.

A major focus of tumor immunology is to reveal the potential role and capacity of immunocompetent cells found in different solid tumor tissues. The most abundant infiltrating cells (TIL), the T lymphocytes have been investigated in details concerning T-cell receptor usage and specificity. However, B cells have hardly been investigated in this respect, although high cellular B-cell infiltration has been correlated with improved patients' survival in some breast carcinomas. This led to our objectives to study variable region gene usage of the tumor-infiltrating B cells in different breast carcinoma types. By defining the immunoglobulin repertoire of the tumor-infiltrating B lymphocytes in the most common invasive ductal carcinoma (IDC) of the breast we compared it to the rare medullary breast carcinoma (MBC). After phenotyping infiltrating ductal carcinomas, B cells were obtained from tumor tissue by microdissection technique. Numerous rearranged TIL-B immunoglobulin heavy chain V genes (VH) were amplified, cloned, sequenced, and comparatively analyzed. Some characteristics were found for both breast carcinoma types. The immunoglobulins produced by TIL-B in ductal carcinoma are highly matured and oligoclonal. We conclude that Ig variable region gene usage reveals similar and distinguishable characteristics of TIL-B immunoglobulin repertoires, which are representative of the nature of the immune responses in invasive ductal and medullary breast carcinomas.

B-Lymphocytes↗
PubMed2005

Characteristic adsorption functions and the surface structure of solid adsorbents.

A thermodynamic model of gas/solid adsorption has been constructed from two elements. The first is the original Gibbs equation. The second consists of functions psi(Theta) or psi(P) that are calculable from measured isotherms. Based on this model the characteristic adsorption functions (CAFs) were defined and calculated. The CAFs, which concentrate into one function all measured isotherms having the same change in relative free energy of the surface, are very sensitive to the structure of the adsorbents. This statement was tested with nitrogen isotherms measured at 77 K on well-characterized chemically/physically treated activated carbons prepared from poly(ethylene terephthalate). Changes in the surface structure were followed by small angle X-ray scattering (SAXS). This experimental approach made it possible to observe the correspondence between structural changes and the CAF.

Journal Article↗
PubMed2004

Thermodynamical model and prediction of gas/solid adsorption isotherms.

A thermodynamic model of gas/solid adsorption has been constructed from two elements. One of those is the original Gibbs equation. The second is functions psi(theta) or psi(P) calculable from measured isotherms. The model provides the possibility of calculating the relative change in free energy of the surface, and based on the model, implicit isotherm equations of general validity and in integral form can be derived. The prediction of isotherms can be made based on characteristic adsorption functions (CAFs). The CAFs concentrate in one function all measured isotherms having the same change in relative free energy of the surface. From CAFs any isotherm can be predicted if one measured point is known or one required datum of the isotherm can be defined. The maximum average deviation between the measured adsorbed amounts and those calculated from the CAFs is +/-10%. The CAFs are very sensitive to the internal structure of adsorbents (micro-, meso-, and macropores and nanostructures). It is the goal of future investigations to determine the exact connections related to the CAFs and to the structure of adsorbents.

Journal Article↗
PubMed2004

Subareolar injection of radioactive colloid for sentinel lymph node identification in breast cancer patients.

Sentinel lymph node biopsy (SLNB) is becoming the standard for staging the axilla in breast cancer patients in many institutions. The best method of injection is still questionable. The purpose of this study was to compare the results of SLNB using the peritumoral or the subareolar injection site. Between December 1997 and March 2000, we performed 100 SLNBs. Technecium-labeled colloidal human serum albumin was injected peritumorally (Group A, 31 patients; Group B, 31 patients) or subareolarly (Group C, 38 patients). Patent blue dye was given periareolarly (Group A) or peritumorally (Groups B and C). Preoperative lymphoscintigraphy was performed in all patients. SLNB was successful in 94 patients (94%). The identification rate improved from 80 per cent (first 25 patients) to 99 per cent (last 75). The subareolar injection of the colloid did not adversely influence the results of SLNB compared with the peritumoral injection (identification rate, 100% vs 97%; false negative rate, 6% vs 14%). The subareolar injection of colloid is a simple and at least as accurate technique as the peritumoral one. This technique can also improve the identification rate of SLNB for breast cancer patients.

Axilla↗
PubMed2003

On thermodynamical inconsistency of isotherm equations: Gibbs's thermodynamics.

It has been proven that all isotherm equations which include the expression 1-Theta contradict the exact Gibbs thermodynamics. These contradictions have been discussed in detail in the case of the Langmuir (L) equation applied to gas/solid (G/S), solid/liquid (S/L), and gas/liquid (G/L) interfaces. In G/S adsorption the L equation can theoretically be applied only at low equilibrium pressures on condition that vg >> vs . vg is the molar volume of the adsorbed amount in the gas phase and vs is the same in the Gibbs phase. In S/L and G/L adsorption the L equation is practically applicable only in the domain of very low concentrations. The cause of these contradictions (inconsistencies) is that Gibbs thermodynamics takes excess adsorbed amounts into account; however, the L and other isotherm equations calculate with the absolute adsorbed amount. The two amounts may be practically equal to each other when the limiting conditions mentioned above are fulfilled. It is also discussed how these inconsistent isotherm equations can be transformed into consistent ones.

Journal Article↗
PubMed2000

[Angiocentric T-cell lymphoma]

SUMMARY: The CD20+ variant of angiocentric T-cell lymphoma is an unusual type of T-cell lymphomas that present cystic changes in organs because of ischaemic necroses. The purpose of this study was to describe a case of CD20+angiocentric T-cell lymphoma, discussing its clinical, histopathological and immunohistochemical features, to analyze its proliferation kinetics and to consider its possible relationship to the Epstein-Barr virus (EBV) to understand better the pathobiological nature of the disease. METHODS: The clinical, histopathological, immunohistochemical and single-cell DNA cytophotometric features of the case were analyzed. In addition in situ hybridization was performed to detect EBV. RESULTS: The 24 years old woman was admitted to our Institute because of pain in the abdominal region and weight loss. There were enlarged lymph nodes on the neck, and biopsy was done. Histological diagnosis: angiocentric T-cell lymphoma, CD20+ variant. CD3, CD43, CD45RA and CD45R0 antigens were positive in the atypic lymphoid cells of the tumour and in cells infiltrating the vascular wall. DNA index was 0.8589 (hypodiploid). Tumour cells in G1 phase: 47%, S phase: 45.4%, G2 phase: 7.6%. Combined chemotherapy was administered because of clinical stadium IV/B of malignant lymphoma (5 CHOP-Bleo, CEPP, CEP, CMVE treatment). The disease showed gradual progression and the patient died 14 months after the first symptoms had appeared. CONCLUSIONS: In the last 13 years there were 5 cases of angiocentric T-cell lymphoma at our Institute. The CD20+ variant is rare, its clinical symptoms are special, the prognosis is unfavourable. The cause why we demonstrate this case is to call attention to a new treatment for these patients by immunotherapy using monoclonal antibodies against CD20 antigen.

Journal Article↗
PubMed2000

Calculation of the BET-Compatible Surface Area from Any Type I Isotherms Measured above the Critical Temperature.

In our previous papers [Tóth, J., et al., J. Colloid Interface Sci. 212, 402 (1999); 212, 411 (1999)] it has been proven that a BET-compatible specific surface area, a(s)(c)(N(2), 77), can be calculated from any Type I monolayer isotherms and from the monolayer domain of Type II isotherms, both measured below the critical temperature. In this paper, the calculation of a(s)(c)(N(2), 77) from Type I isotherms at temperatures above the critical temperature is discussed. These calculations are also based on the thermodynamical consistent form of the Tóth (T) equation. This relationship can be derived from the differential equation dn(s)/n(s)=[psi(p)](-1)dp/p, where the function psi(p) is calculable from the measured isotherms and includes the change in the surface free energy. The basic problem of the calculation of a(s)(c)(N(2), 77) is the determination of the upper limit of integration (p(u)) required to solve this differential equation. It is demonstrated that p(u) can be calculated from the equation ln(p(u))=-alphaT(-1)+beta. The constants alpha and beta are independent of the temperature of the isotherms but they are very sensitive to the structure of adsorbents and to the quality of adsorptives. This fact also makes it possible to characterize exactly the nanostructure of solids and the state of adsorptives. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

[Expression of HER2 in breast cancer]

In breast cancer the membrane expression of HER2 receptor protein encoded by the HER2 proto-oncogene seems to have an ever growing clinical significance. In tissue cultures and animal experiments it was shown that the HER2 gene amplification induces malignant transformation and intensifies the aggressiveness of the tumour cells. Correlating with the so called pheno-and genotypic prognostic markers, the overexpression of HER2 in breast cancer predicts also poor prognosis and indicates enhanced potential for metastatisation. In some of the so called precancerous proliferations and "in situ" carcinomas we demonstrated the enhanced membrane staining of the HER2 receptor protein. In these cases we frequently observed DNA aneuploidy,the presence of p53 mutational protein and CD44v6 glycoprotein. The immunohistochemical studies of HER2 protein in invasive carcinomas have revealed, an interrelationship between the grade of differentiation, histological type, aggressiveness and biological behaviour of the "in situ" and invasive carcinomas. In clinical studies trastuzumab, a humanized monoclonal antibody recognizing extracellular domain of HER2 receptor protein, has proved to be effective in HER2 overexpressing metastatic breast cancer either as monotherapy or in combination with chemotherapeutical agents. The DAKO "HercepTest" is a semiquantitative, standardised method for the determination of HER2 overexpression.

Journal Article↗
PubMed2000

[Prognostic factors of breast cancer]

OBJECTIVES: Characterization of breast cancers by various tumour markers which are appropriate for the identification of high risk groups. Markers related to the metastasis cascade and tumour recurrence have been investigated. MATERIALS AND METHODS: RT-PCR was used to determine the expression of cytokeratin 20 in the bone marrow and sentinel lymph node of breast cancer patients (n=45). The expression of HER2, Cadherin E, Cyclin D, Bcl2 and Bax has been evaluated by Western blot (n=744 invasive ductal carcinomas and 117 invasive lobular carcinomas, 124 recurrent breast cancers). Mutations of p53, APC and beta Catenin genes were detected by PCR-SSCP method. RESULTS: Expression of cytokeratin 20 was found in 30% of the bone marrow samples indicating the presence of micrometastasis. The level of Cyclin D, HER2 and Bcl2 is elevated four-fold in the recurrent breast cancers. The metastasis of invasive ductal carcinomas is accompained by high frequency of p53 mutations (24%) and APC mutations (18%). The invasive lobular carcinomas could be characterized with low frequency of p53 mutation (3%), low level of Cadherin E and high level of catenin beta. CONCLUSIONS: Identification of micrometastasis can promote the development of therapeutic strategy. Evaluation of HER2 level and determination of p53 mutations contribute to the identification of high risk patients. Our results suggest that the progression of invasive ductal carcinomas depends on the APC mutations, while metastasis of invasive lobular carcinomas depends on beta catenin mutations.

Journal Article↗
PubMed1996

Lack of Correlation Between Survival and Allele Loss on Chromosome 7q31-32 in Primary Breast Cancer.

High incidence of loss of heterozygosity (LOH), affecting the 7q31-32 chromosome region in sporadic primary human breast carcinomas suggests the presence of a tumor suppressor gene in this region which seems relevant to the development of breast cancer. To further determine the possible role of this region in the pathogenesis of human primary breast cancer and association with survival, LOH analysis was performed on 52 primary breast cancer patients using a set of highly polymorphic microsatellite markers. Our panel contained twenty biopsy cases of unknown survival, nineteen cases with more than five years survival and fourteen cases with less than two years survival. Corresponding normal and tumor DNAs were analyzed by polymerase chain reaction (PCR). The data presented here demonstrate that all patients were informative at least at one locus and 20 (38%) out of 53 cases showed LOH at one or more loci on chromosome 7q31-32. Relatively high incidence of LOH (34%) was detected at the D7S522 microsatellite marker located near to the cMet proto-oncogene while lower frequencies were observed at D7S523 (19%) and D7S495 (17%) loci, supporting the existence of a putative tumor suppressor gene at the chromosome 7q31.1 region. Our results suggest that allelic imbalance on 7q may occur at an early stage of breast carcinogenesis, as no correlation was observed between allelic loss and clinico-pathological data.

Journal Article↗
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

Microvascular density of breast cancer in bone metastasis: influence of therapy.

BACKGROUND: Bone is the most frequent site of systemic progression of breast cancer (BRC). Angiosuppressive therapy has now entered the management of progressing cancers, therefore it is clinically important to obtain information on vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) of bone metastasis of BRC. MATERIALS AND METHODS: VEGF expression and MVD were evaluated in bone metastases of BRC immunohistochemically in paraffin samples of 18 patients and compared to their primary tumors. MVD was determined by using the hot-spot method and the endothelial marker, CD34. RESULTS: Chemo- and/or endocrine therapy-naïve BRC cases progressed to the bone with a concomitant increase in their angiogenic potential, suggesting that this is the "natural history" of BRC progression. On the other hand, this study revealed that vascularization of the bone metastases of BRC patients that had received adjuvant (chemo- and/or endocrine) therapy was significantly decreased compared to the corresponding primary tumors, also supported by a decreased VEGF expression in metastases, both suggesting that the treatment significantly affected the angiogenic phenotype of the progressing disease. CONCLUSION: Angiosuppressive therapy is a new approach to cancer management including BRC and is frequently applied in the advanced stage of disease. Tumors with a prominent angiogenic phenotype (high MVD and VEGF) are primary candidates for such regimes. The fact that chemo-endocrine adjuvant therapy of BRC resulted in a weaker angiogenic phenotype in bone metastases compared to non-treated cases may suggest that these latter patients are better candidates for angiosuppressive interventions.

Adult↗