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Gábor Kovács

Publications and source records attributed to Gábor Kovács.

At least 19 recordsLinked to original sources
PubMed2007

[Developments in cancer management by innovative genomics. 2006 report of the National Cancer Consortium].

Research on developing molecular diagnostics for hereditary cancers resulted in establishing diagnostic services for familiar polyposis and non-polyposis patients (mutation determination of APC, MYH, STK11, SMAD4, MLH1, MSH2). In familiar testicular cancers the role of gr/gr gene on Y chromosome was identified. Molecular diagnostic tool was established to monitor the progression of follicular lymphoma using Bcl-2/IgH fusion sequences. Molecular diagnostic tools were developed to monitor circulating endothelial precursor cells (CEP) as well and the technique was tested in lung cancer patients. In malignant melanoma we have tested several potential novel markers among which ryanodine receptor seems to be a promising one, while the functional P2X7 receptor may serve as a therapeutic target. We have determined the tyrosine kinase "kinome" profile of HER-2-amplified breast cancers. Furthermore, the "kinome" profile was found to be characteristic for head and neck cancers of various anatomical location. Based on previous studies on the anti-migratory and antimetastatic potential of low-molecular-weight heparins, we have identified short heparin-derived oligosaccharides with maintained antimetastatic- but non-anticoagulant potentials. Pharmacogenomic studies on the role of polymorphism of the serine-hydroxymethyl-transferase (SHMT) gene in the efficacy of 5-FU and FOLFIRI protocols of colorectal cancer patients revealed a significant effect resulting in altered overall survival as well.

Antineoplastic Agents↗
PubMed2007

Multipoint interphase FISH in childhood T-acute lymphoblastic leukemia detects subpopulations that carry different chromosome 3 aberrations.

We examined chromosome 3 in 32 childhood acute lymphoblastic leukemia (ALL) bone marrow samples. Using interphase multipoint FISH (mp-FISH), which was developed by our group, with 42 chromosome 3-specific probes, we detected clonal chromosome 3 aberrations in 4 T-cell ALL (T-ALL) cases. Four out of seven T-ALL cases carried 3q trisomies. One T-ALL case carried either trisomy 3 (in 15% of the cells) or a 23-megabase (Mb) 3p13 approximately p12 deletion in a different subpopulation of cells of 32%. Another T-ALL case had either 3q trisomy in 11% or a 12-Mb 3p12 approximately p13 deletion in 19% of the cells. The deletions were overlapping. In both cases, the majority of the bone marrow cells (47 and 70%, respectively) were normal chromosome 3 disomics. The interstitial deletions detected harbor a known homozygous deletion region between 72.6 and 78.8 Mb, which has been described in lung and breast tumors and contains the DUTT1/ROBO1 tumor suppressor gene. These deletions detected by mp-FISH would have remained unnoticed by conventional cytogenetics and multiplex FISH, as well as by current methods based on total tumor DNA analysis such as comparative genomic hybridization (CGH), array CGH, and loss of heterozygosity (LOH).

Adolescent↗
PubMed2006

The new 2,3-benzodiazepine derivative EGIS-8332 inhibits AMPA/kainate ion channels and cell death.

We observed in vitro neuroprotective and AMPA/kainate receptor antagonist effects of the new 2,3-benzodiazepine derivative EGIS-8332 (R,S-1-(4-aminophenyl)-7,8-methylenedioxy-4-cyano-4-methyl-3-N-acetyl-5H-3,4-dihydro-2,3-benzodiazepine) using the lactate dehydrogenase (LDH) release assay and patch clamp recordings on primary cultures of rat embryonic telencephalon neurons exposed to AMPA/kainate receptor agonists. EGIS-8332 potently decreased alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and quisqualate induced LDH release (IC(50)=5.2+/-0.4 and 7.4+/-1.3 microM, respectively) from the cells. Whole-cell patch clamp studies carried out on the ionotropic glutamate receptors N-methyl D-aspartate (NMDA), as well as AMPA (and kainate) in cultured telencephalon neurons verified that EGIS-8332 blocked steady state responses to AMPA and kainate (IC(50)=1.7+/-0.4 and 6.2+/-1.6 microM, respectively), but hardly influenced currents evoked by NMDA. EGIS-8332 also inhibited kainate-evoked response in CHO cells expressing the flop variant of GluR1 receptor and, in cerebellar Purkinje cells at similar efficiency. The stereoselectivity of the inhibitory site is established by the clearly dissimilar inhibitory potency of the enantiomer components of EGIS-8332 differing in the configuration of methyl and cyano substituents on carbon C(4): the R(-) enantiomer was found to be the efficient species. This finding suggests that the inhibitory interaction between the channel protein and drug is promoted by presence of the C(4) methyl group. The inhibition of the AMPA/kainate ion channels by EGIS-8332 is non-competitive, not use dependent, and depends neither on the closed/open state of the channel, nor the membrane potential. These findings suggest an allosteric mechanism for the inhibition. These in vitro observations suggest that the compound might be useful in the treatments of certain acute and chronic neurological syndromes initiated by derangements of ionotropic glutamate receptor function.

Animals↗
PubMed2006

[An interdisciplinary malignancy, the lung cancer in Hungary in 2006: epidemiology, prevention and access to therapy].

The most frequent malignant tumor is lung cancer all around the world. Mortality rate is highest in Hungary. The frequency accumulates in the Southern part of the country. Early radical resection is the really effective treatment of the disease, which can bring the chance of longer survival. The methods of prevention, such as restrain of smoking and early detection with targeted examinations of the risk groups need more attention. There are unacceptable differences among regions in Hungary on the field of the accessibility to the adequate therapies. There are three-fold differences in the rate of operation and radiotherapy between certain counties. The frequency of the chemotherapy is acceptable, but there are some centers which do not use the recommended modern protocols. Professional supervisors and inspectors must give marked attention to the quality control of lung cancer therapies to provide equal chances to patients, independently of their residence.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

[Hungarian experience with non-Hodgkin's lymphoma in childhood].

Between 1990 and 2004, 230 children with non-Hodgkin's lymphoma (NHL) were treated according to the Berlin-Frankfurt-Münster (BFM) protocols (NHL-BFM-90 and -95) in Hungary. The aim of the present study was to summarize our experience with these protocols, to assess the survival rates and to compare the Hungarian data with the international results. The male-to-female ratio was 2.59:1, the mean age at the time of diagnosis was 10 years and 1 month. Ninety-one children had lymphoblastic/T-NHL (LB/T-NHL), 108 B-NHL and 31 anaplastic large cell lymphoma (ALCL). Twenty-eight patients had relapse after a mean time of 13 months from the time of the initial diagnosis. In the above mentioned period, 16 children underwent autologous stem-cell transplantation. Nine patients with B-NHL got anti-CD20 immunotherapy. The five-year overall survival (OS) of our patients is 77.8%+/-3%, the event-free survival (EFS) is 75.1%+/-3%. The 5-year OS and EFS rates were not statistically different in the three histology groups (OS: 71.6%+/-5%, 82.7%+/-4% and 80.3%+/-7%; EFS: 68.7%+/-5%, 81.1%+/-4% and 73.9%+/-8% in LB/T-NHL, B-NHL and ALCL, respectively). We can conclude that non-Hodgkin's lymphoma has a quite good prognosis among the malignant pediatric diseases. The cure rate is over 75%. The Hungarian results are comparable with other international data. In the last five years the mortality during induction was reduced from 10% to 2% and the OS is about 10% better than it was before. In case of relapse or residual disease, therapeutic results can be improved with stem-cell transplantation with or without immunotherapy.

Adolescent↗
PubMed2006

[The function of the immune system after the treatment of pediatric malignant diseases].

INTRODUCTION: Currently, malignancies in childhood can be cured in 70 percent of the cases. However, the intensive cytostatic therapy may lead to late side effects influencing quality of life. AIM OF THE STUDY: Analysis of the reconvalescence of the immune functions after completion of therapy for malignancies in children. PATIENTS: 88 long-term survivors (51 boys, 37 girls) were investigated (43 acute lymphoid leukemia, 15 lymphoma, 20 bone tumors, 10 other solid tumors). Mean age at the time of diagnosis was 7.8 years (1 mo-17.7 years). METHODS: The following parameters were investigated: serum immunoglobulin levels after completion of the chemotherapy and in the next 4 years thereafter, lymphocyte subpopulations in the peripheral blood by flow-cytometry and cellular immunity by in vitro tests (natural killer activity, antibody-dependent cellular cytotoxicity, mitogen-induced T- and B-cell blastic transformations). RESULTS: Lower serum immunoglobulin (IgG) levels could be detected in patients with leukemia after completion of the chemotherapy (8.8 +/- 3.2 g/l). One year thereafter serum IgG levels increased significantly (10.1 +/- 2.9 g/l) (p<0.05). In patients with solid tumors the serum IgG levels were in the normal range at the end of the chemotherapy (12.1 +/- 4.3 g/l). At a mean of 1.3 years after the end of chemotherapy NK activity decreased in 7/43 (16.3%) leukemia patients, and in 3/45 (6.7%) solid tumor patients, ADCC decreased in 8/43 (18.6%) and 3/45 (6.7%), respectively (p<0.05 leukemia vs. solid tumor). At a mean of 15 months after the end of the therapy B-cell blastic transformation was decreased in 3/43 (7%) leukemia patients and in 4/45 (8.9%) solid tumor patients. At the same time point T-cell blastic transformation was altered in 5/43 (11.6%) and in 4/45 (8.9%) cases, respectively. CONCLUSION: Cytotoxic therapies lead to severe, long-term depression of the immune system. At the end of the chemotherapy this effect is more pronounced in leukemia patients. Years (1.5-3) after completion of the therapy in a significant proportion of the patients some in vitro parameters of the immune system are yet altered, so careful monitoring of this patient population is mandatory.

Adolescent↗
PubMed2006

Karyotype complexity and VH gene status in B-cell chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia-related genomic changes were analyzed by karyotyping, fluorescence in situ hybridization, and V(H) gene sequencing in a prospective clinical evaluation. The V(H) mutational status correlated with high-risk cytogenetic aberrations while no such relation could be demonstrated for specific VH gene usage (V(3-21) and V(1-69)). Complex karyotypes were highly indicative of disease progression.

Chromosome Aberrations↗
PubMed2006

[Subacute cardiotoxicity caused by anthracycline therapy in children: can dexrazoxane prevent this effect?].

OBJECTIVES: The use of anthracyclines are limited by their cardiotoxic side effects (first of all congestive cardiomyopathy). In this study we analyzed the anthracycline-induced cardiotoxicity and the possible preventive role of dexrazoxane in children. PATIENTS: 158 anthracycline-treated long-term survivors could be analyzed. Sixty-one children received dexrazoxane (group D) and 97 patients received anthracyclines only (group C). METHODS: Cardiac ultrasound examinations (ECHO) and electrocardiograms (ECG) were performed regularly from the beginning of chemotherapy and yearly thereafter. Shortening fraction (FS) was used as indicator of the ventricular function. RESULTS: The incidence of reduced left ventricular function (FS) was 13.4% in C, and 8.2% in D (p=ns). Two years after completion of the chemotherapy FS was reduced in 13.7% in C and 0% in D, respectively (p=0.056), and 5 years after therapy in 11.0% in C and 2.4% in D, respectively (P=0.034). Left chamber wall diameter was abnormal in systole in 6% in C and 2% in D, in diastole in 11% in C and 7% in D (p=ns) after 3 years of follow-up. CONCLUSION: Anthracycline-induced subacute cardiotoxicity can be significantly diminished by the concomitant use of dexrazoxane. For the final conclusions longer follow-up is necessary.

Adolescent↗
PubMed2006

Hardware modification of a 7 mm MAS NMR probe to a single-crystal goniometer.

Tensorial terms of the Hamiltonian can be measured by solid-state single-crystal nuclear magnetic resonance (NMR) spectroscopy which requires a goniometer NMR probehead. Goniometer probes; however, are not standard parts of solid NMR spectrometers and are available only at a much higher price than magic-angle spinning (MAS) probeheads widely used in research. Due to requirements of MAS experiments, modern probeheads are designed for small ceramic rotors, which are 1-4 mm in diameter, to reach very high angular frequencies, so there are several older 7 mm MAS probeheads used rarely todays in NMR laboratories. In this paper, a simple method is presented how to rebuild step-by-step a 7 mm Bruker MAS probehead to be suitable for single-crystal spectroscopy. In the second part (31)P chemical shift tensors of Na(4)P(2)O(7) x 10H(2)O are determined to demonstrate the functionality of the rebuilt probehead.

Journal Article↗
PubMed2006

Jumping translocation of 17q11 approximately qter and 3q25 approximately q28 duplication in a variant Philadelphia t(9;14;22)(q34;q32;q11) in a childhood chronic myelogenous leukemia.

The virtually obligatory presence of the Philadelphia chromosome may suggest a causal homogeneity, but chronic myelogenous leukemia (CML) is a clinically heterogeneous disease. This may be a consequence of the variable BCR breakpoints on chromosome 22 and of nonrandom secondary chromosomal abnormalities. We present the case of a boy, age 12, investigated in blastic phase of CML. Karyotyping with conventional and multiplex fluorescence in situ hybridization (FISH and M-FISH) karyotyping, complemented with reverse transcriptase-polymerase chain reaction, identified a variant Philadelphia translocation t(9;14;22)(q34;q32;q11) involving a cryptic BCR/ABL fusion with formation of the p190(Bcr-Abl) oncoprotein. M-FISH revealed also an unbalanced jumping translocation of 17q11 approximately qter alternatively present on chromosomes 14 or 20, apparently hithertofore unreported in hematological malignancies. Another secondary aberration, dup(3)(q25q28), was revealed by multipoint interphase FISH (mpI-FISH). Gain of this region is known in adult hematological malignancies and solid tumors, suggesting its general involvement in tumor initiation or progression (or both), regardless of tissue origin.

Child↗
PubMed2006

Hungarian experience with Langerhans cell histiocytosis in childhood.

The Langerhans cell histiocytosis (LCH) in children is relatively rare and the long-term analysis of therapy results has not been done yet in Hungary. The aim of this study was to investigate the incidence, clinical features, prognostic risk factors, and treatment results of children's LCH in Hungary in a 20-year period. Children less than 18 years of age with newly diagnosed LCH in Hungary were entered in this study. Clinical data of all children with LCH were reported to the National Childhood Cancer Registry in Hungary from 1981 to 2000. The clinical files were collected and abstracted for information regarding age at diagnosis, gender, disease characteristics, treatment, and outcome of treatment. Median follow-up duration of surviving patients is 10.98 years. Between January 1981 and December 2000, 111 children under 18 years of age were newly diagnosed with LCH in Hungary. The annual incidence of LCH in children younger than 18 years of age was 2.24/million children. The male-female ratio was 1.36:1; the mean age was 4 years 11 months. Thirty-eight children had localized disease and in 73 cases systemic dissemination was found already at the time of diagnosis. Twenty-two patients were treated only by local surgery, 7 by surgery with local irradiation, and 5 children got only local irradiation. In 2 cases remission was achieved with local steroid administration. Seventy-five patients received chemotherapy. In the 20 years of the study 14 children died, 9 due to the progression of the disease. Sixteen patients had relapse with a mean of 2.16 +/- 1.29 years after the first diagnosis. Three patients with relapse got chemotherapy generally used in lymphoma and remission was achieved. The overall survival of all patients (n = 111) was 88.3 +/- 3.1% at 5 years and 87.3 +/- 3.2% at 10 and 20 years. Childhood LCH is a well-treatable disease and the survival rate is high. Even disseminated diseases have a quite good prognosis in childhood.

Adolescent↗
PubMed2006

Multipoint interphase FISH analysis of chromosome 3 abnormalities in 28 childhood AML patients.

We detected non-random 3p losses and 3q gains on well-determined regions in both murine and human tumors using a microcell hybrid-based model system called 'elimination test'. We suggest that these are general malignancy-associated aberrations not necessarily linked to a particular tissue of origin. To examine chromosome 3 abnormalities, in 28 childhood acute myeloid leukemia bone marrow samples, we performed interphase multipoint-fluorescence in situ hybridization using 84 chromosome 3-specific probes and detected clonal chromosome 3 aberrations in nine cases, which is of a higher frequency than the previously reported one. In 3/28 children, a chromosome 3 abnormality was detected which was not visible using conventional cytogenetic analysis. We did not detect any 3p deletion. Increased copy number of 3q was found in four cases with trisomy of whole chromosome 3 and one case with 3q tetrasomy (isodisomy). We identified rare structural rearrangements in childhood acute myeloblastic leukemia, involving 3q21 and 3q26 loci around RPN1 and MDS1/EVI1 respectively. The poor outcome in pediatric patients with 3q rearrangements appears to be quite uniform.

Acute Disease↗
PubMed2006

[Endocrine side effects among psychiatric patients treated with antipsychotics].

UNLABELLED: The increased serum prolactin is one of the side effects of antipsychotic treatment. The clinical signs of its elevated level are galactorrhea, gynecomastia, breast tenderness and sexual dysfunction. These symptoms can cause poor compliance and relapse of the psychiatric illnesses. The possible clinical interventions are: 1) reduce of the dose of the psychotropic drug and/or addition of a dopamine agonist; 2) switch to another drug. The aim of our study was to evaluate the results of the switch to quetiapine in the cases of elevated prolactin with galactorrhea. METHODS AND PATIENTS: Five of our patients (from the January to July in 2005) treated for more than two months with new generation antipsychotics had the symptoms of galactorrhea/breast tenderness. The diagnoses in according to ICD-10 were: schizophrenia and schizoaffective disorder. The differential-diagnostic examination were: physical, neuroimaging and laboratory including prolactin level followed up on the 4th, 8th weeks after the therapeutical intervention. RESULTS: The galactorrhoea disappeared and prolactin levels normalized after the switching to quetiapine. In the case of bromocriptine addition to previous therapy symptom stopped but the hormone level did not change significantly. There was remission and/or stabilisation of psychotic symptoms with quetiapine. CONCLUSION: The galactorrhea is one of the possible side effects of psychotropic drugs. We presented five patients with this kind of symptoms related to antipsychotic treatment. After the switch to quetiapine the galactorrhea and breast tenderness stopped, the level of prolactin normalized and the psychiatric condition of the patients showed remission. Our data support the benefit of the switch to another new generation drug, first of all to quetiapine, in the cases of galactorrhea and/or elevated prolactin level related to the antipsychotic pharmacotherapy.

Adult↗
PubMed2005

[Identification of 3q21q26 syndrome by "multipoint" interphase FISH analyses in childhood myeloid leukemia].

Cytogenetic syndrome involving bands 3q21 and 3q26, known as "3q21q26 syndrome" has been observed in adult patients with acute myelogenous leukemia (0.5-2%), chronic myelogenous leukemia in blast crisis (20%), myelodysplastic syndromes and myeloproliferative disorders. In the present study bone marrow samples from two boys (12 and 16 years), diagnosed with CML and AML respectively, were investigated using conventional cytogenetic methods, interphase "multipoint" fluorescence in situ hybridization (FISH), dual color-FISH and multiplex FISH. The "multipoint" FISH analysis identified in de novo childhood AML case an inv(3)(q21q26) and a complex 3q rearrangement including inversion and duplication in the CML case. The "3q21q26 syndrome" is associated with normal or elevated platelet counts with marked abnormalities of megakaryocytopoiesis, involvement of multiple hematopoietic lineages. The affected patients were resistant to conventional chemotherapy and had a short survival. This syndrome is very rare in de novo childhood AML, and simultaneous presence of 3q inversion and duplication, to our knowledge, has not yet been identified in hematological malignancies. The results of our study emphasize the importance of classical and modern cytogenetic analysis in the diagnosis of hematologic malignancies, because in the majority of cases they can provide additional diagnostic information for the clinicians in deciding the best therapeutic approach, precise classification and prognosis of the disease.

Adolescent↗
PubMed2005

[New therapies for non-small cell lung cancer].

Lung cancer is one of the most frequent causes of death from cancer. Non-small cell lung cancer represents approximately 80% of the total pulmonary malignancies. Unfortunately, most non-small cell lung cancer patients present advanced disease at diagnosis and a very poor prognosis. Despite advances in our understanding of the molecular and genetic basis of non-small cell lung cancer, and improvement in therapy with surgery, conventional chemotherapy, and radiation, 5-year survival for patients with this diagnosis remains poor and the disease remains a clinical challenge. However, strategies of molecular based therapies are in development and it is hoped that these new approaches will continue to improve survival for patients with advanced lung cancer. Any categorization of these drugs is hard, with overlap in several features. The main investigated agents are epidermal growth factor receptor (EGFR) family inhibitors, angiogenesis inhibitors and antivascular drugs, signal transduction inhibitors, apoptosis inducers, eicosanoid pathway inhibitors and immunotherapeutic drugs. To date, few of these new drugs can offer trust of a substantial influence on the natural history of non-small cell lung cancer, and disappointing results are more commonly reported than encouraging ones. Nevertheless, tailored treatment for non-small cell lung cancer patients may represent a further chance of tumor control and symptom palliation. This review presents an overview of molecular targeted therapy in non-small cell lung cancer.

Angiogenesis Inhibitors↗
PubMed2005

[Experiences with Langerhans' cell histiocytosis in children in Hungary].

BACKGROUND: Langerhans cell histiocytosis (LCH) in children is relatively rare, and the long-term analysis of therapy results has not been done yet in Hungary. PURPOSE: In this review we summarise the incidence, clinical features, prognostic risk factors and treatment results of children's LCH in Hungary, using data from the National Childhood Cancer Registry in Hungary in a 20-year period between 1981 and 2000. RESULTS: From January 1981 to December 2000, 111 children under 18 years of age were newly diagnosed with LCH in Hungary. The male-female ratio was 1.36:1, the mean age: 4 years 11 months. The minimal and median follow-up time was 3.48 years and 10.98 years respectively. 38 children had single-system disease, while in 73 cases we found systemic dissemination already at the time of diagnosis. Twenty-two patients were treated only by local surgery, 7 by surgery with local irradiation and 5 children received only local irradiation. In two cases remission was obtained with local steroid administration. 75 patient received chemotherapy. During the twenty years 14 children died, 9 due to the progression of the disease. Sixteen of the 111 patients had relapse with a mean of 2.16+/-1.29 years after the first diagnosis. Three patients with relapse got chemotherapy generally used in lymphoma and remission was achieved. The overall survival of all patients (n=111) was 88.3+/-3.1% at 5 years and 87.3+/-3.2% at 10 and 20 years. CONCLUSION: Childhood LCH is a well treatable disease and the survival rate is high. Even disseminated diseases have a quite good prognosis in childhood.

Adolescent↗