Biomedical subjects

Zoltán Hanzély

Publications and source records attributed to Zoltán Hanzély.

7 recordsLinked to original sources

PubMed2006

Expression and prognostic examination of heat shock proteins (HSP 27, HSP 70, and HSP 90) in medulloblastoma.

Expression of heat shock proteins (HSPs) is of prognostic significance in several tumor types. HSP expression levels were determined in medulloblastomas and tested whether HSPs expression was associated with prognostic parameters. Expression of antiapoptotic HSP 27, HSP 70, and HSP 90 was investigated by immunohistochemistry, on paraffin-embedded sections from 65 patients. Expression of HSPs was validated on internal vascular controls and by Western blotting analysis. Sample evaluation was based on the estimated percentage of HSP positive tumor cells. For survival analysis Kaplan-Meier method, for statistical analysis chi2 test, univariate analysis, and log rank test were applied. Expression of HSPs varied in medulloblastomas. On the basis of the average expression rate of HSPs, at HSP 27 and HSP 90 with a 10% cut off, and at HSP 70 with a 70% cut off 2 groups were created. The amount of expression of any of the HSP types was not significantly associated with known prognostic factors (age of patient, extent of resection, presence of metastasis) and histologic subtype. After an average follow-up period of 4.30 years, no significant difference was observed in survival depending on the expression of HSP 27 or HSP 70 or HSP 90. The high expression of HSPs indicates that these proteins are potential therapeutic targets.

Adolescent↗

PubMed2006

Somatostatin analogues stimulate p27 expression and inhibit the MAP kinase pathway in pituitary tumours.

OBJECTIVES: Somatostatin (SST) analogues play an important role in the medical management of somatotroph pituitary adenomas and new agonists have the potential to be effective in a wider group of pituitary and other tumours. The anti-proliferative effect of SST occurs through multiple mechanisms, one of which is cell-cycle arrest, where p27, a cyclin-dependent kinase inhibitor, is an important regulator. We hypothesised that SST may upregulate p27 protein levels and downregulate the MAP kinase pathway in these tumours. METHODS: Human pituitary adenoma cells and rat pituitary cell line (GH3) were cultured and treated in vitro with octreotide and the broad-spectrum SST agonist SOM230 (pasireotide). Immunoblotting for p27 and phospho-ERK (pERK) was performed and proliferation assessed by [3H]-thymidine incorporation. Histological samples from acromegalic patients treated with octreotide before surgery were immunostained for p27 and compared to samples from untreated patients matched for sex, age, tumour size, extension and invasiveness. RESULTS: We detected upregulation of p27 protein levels with SST analogue treatment in vitro in human pituitary adenoma samples. pERK1/2 was inhibited by SST analogues in both the human samples and GH3 cells. SST and its analogues inhibited the proliferation of GH3 cells. p27 immunostaining was stronger in samples from patients with longer preoperative octreotide treatment (more than 6 months) than in samples from patients with shorter treatment periods. CONCLUSIONS: This study demonstrates that SST-mediated growth inhibition is associated with the downregulation of pERK and upregulation of p27. More potent and broader-spectrum SST analogues are likely to play an increasing role in the treatment of tumours, where the MAP kinase pathway is overactivated.

Adenoma↗

PubMed2006

Erdheim-Chester's disease of the heart: a diagnostic conundrum and collision with the same mass in the orbit.

Erdheim-Chester's disease is a rare multisystem xanthogranulomatosis, afflicting the skeletal system with the occasional involvement of soft tissues. We delineate an unusual case of a cardiac variant of Erdheim-Chester's disease presenting with pericardial effusion and as a collision with a synchronous orbital manifestation. We describe our diagnostic pathway and propose a novel treatment option involving nonsteroidal anti-inflammatory drugs. The role of cyclo-oxygenase in the disease process and inhibition thereof by NSAIDs is hypothesized and discussed.

Celecoxib↗

PubMed2005

Differential gene expression in pituitary adenomas by oligonucleotide array analysis.

OBJECTIVES: Microarray technology allows for the expression profile of many thousands of genes to be quantified at the same time, and has resulted in novel discoveries about the tumour biology of a number of cancers. We sought to do this in pituitary adenomas, the most common intracranial neoplasm. METHODS: Affymetrix GeneChip HG-U133A oligonucleotide arrays covering 14 500 well-characterised genes from the human genome were used to study pooled RNA for each of the four major pituitary adenoma subtypes. Individual gene-expression levels in the tumours were compared relative to the expression profile in normal pooled pituitary RNA. Three differentially expressed genes with potential importance in tumourigenesis were chosen for validation by real-time quantitative PCR on the original tumours and on an additional 26 adenomas. RESULTS: Bioinformatic analysis showed that 3906 genes and 351 expressed sequence tags were differentially expressed among all pituitary tumour subtypes. Lysosomal-associated protein transmembrane- 4-beta (LAPTM4B), a novel gene upregulated in hepatocellular carcinoma, was significantly over-expressed in adrenocorticotrophin (ACTH)-secreting adenomas and non-functioning pituitary adenomas (NFPAs). Bcl-2-associated athanogene (BAG1), an anti-apoptotic protein found at high levels in a number of human cancers, was significantly over-expressed in growth hormone-secreting and prolactin-secreting adenomas and NFPAs. The cyclin-dependent kinase inhibitor p18, in which murine gene deletion has been shown to produce pituitary ACTH cell hyperplasia and adenomas, was significantly under-expressed in ACTH-secreting adenomas. CONCLUSIONS: Expression array analysis of pituitary adenomas using the Affymetrix GeneChip HG-U133A arrays appears to be a valid method of identifying genes that may be important in tumour pathogenesis.

Adenoma↗

PubMed2005

Histopathological findings in a surgically resected thalamic cavernous hemangioma 1 year after 40-Gy irradiation.

Stereotactic radiosurgery is a controversial treatment modality in the management of cerebral cavernous hemangiomas (CHs), and results vary from center to center. Even the interpretation of treatment failure is controversial. It is suggested that the systematic pathological investigation of irradiated specimens could help to resolve the controversy. A hemorrhagic lesion in the posterior part of the thalamus had been diagnosed as a tumor and was treated with 40-Gy fractionated radiotherapy. One year after this treatment the case was reconsidered based on new imaging evidence, and the lesion was removed by conventional craniotomy. Histopathological examination revealed a CH with postirradiation changes. Compared with nonirradiated control CH tissue samples, there was endothelial cell destruction and marked fibrosis with scar tissue formation in the stroma of the treated lesion. The histopathological findings in this specimen were similar to those described in arteriovenous malformations after gamma knife surgery. The results of light microscopic investigations suggest that the ionizing effect of radiation energy evokes vascular and connective tissue stroma changes in CHs as well.

Adult↗

PubMed2003

Role of early radiotherapy in the treatment of supratentorial WHO Grade II astrocytomas: long-term results of 97 patients.

OBJECT: To determine principal prognostic factors and the effect of timing of radiotherapy (RT) on disease-specific survival (DSS) and progression-free survival (PFS) in WHO Grade II astrocytomas. METHODS: Histologic slides of 166 consecutive patients with the original tissue diagnosis of low-grade, non-pilocytic astrocytoma were reviewed. One-hundred and six were selected where two additional certified neuropathologist agreed on the grading of WHO Grade II astrocytoma. In 97 out of 106 cases follow-up informations were available. Early postoperative RT was given to 36 out of 97 patients (37%). The two groups of patients (early vs. delayed RT) were well balanced in respect to extent of surgery and other main clinical prognostic factors. Median follow-up of surviving patients was 79 months. The 5- and 10-year PFS was 52.2% and 30.7% with early RT and 39.5% and 12.4% with delayed RT (p = 0.0388). In respect to DSS, there was no significant difference in the 5- and 10-year actuarial survival rate according to the timing of RT (60.5% and 26.5% vs. 66.6% and 23.7%; p = 0.7545). Age (p = 0.0145) and extent of surgery (p = 0.0473) were significant prognostic variables in respect to DSS. Subdividing the irradiated group based on the extent of surgery, early RT in the subtotal group significantly improved 5-year PFS (60.0% vs. 12.4%; p = 0.0036) and DSS (66.7% vs. 49.8%; p = 0.0389). However, postoperative RT had no influence on PFS (p = 0.6812) and DSS (p = 0.3987) in the group with extensive resection. CONCLUSION: Early postoperative RT in subtotally resected, Grade II astrocytomas significantly improves both progression-free and disease-specific survival. Early RT does not benefit patients with extensive resection, RT should be withheld in these patients until progression.

Adolescent↗

PubMed2003

Identification of adrenocorticotropin receptor messenger ribonucleic acid in the human pituitary and its loss of expression in pituitary adenomas.

The ACTH receptor (ACTH-R) is the second member of the melanocortin (MC-2) receptor family that includes five seven-transmembrane G protein-coupled receptors and has been shown to be predominantly expressed in the adrenal cortex. It has been postulated that ACTH may regulate its own secretion through ultra-short-loop feedback within the pituitary. ACTH-secreting adenomas are characterized by resistance to glucocorticoid feedback, and they may have dysregulated ACTH feedback. We therefore investigated the ACTH-R in normal and adenomatous human pituitary tissue. We report here the identification of ACTH-R mRNA in the human pituitary gland, which was confirmed by direct sequencing. We studied the expression of the ACTH-R in 23 normal pituitary specimens and 53 pituitary adenomas (22 ACTH-secreting, nine GH-secreting, eight prolactin-secreting, one TSH-secreting, one FSH-secreting, 10 nonfunctioning, and two silent corticotroph adenomas), using the sensitive technique of real-time quantitative PCR. Contamination of ACTH-secreting adenomas and nonfunctioning pituitary adenomas with nonadenomatous tissue was excluded by lack of Pit-1 expression. ACTH-R mRNA was detected in all normal pituitary specimens, and in situ hybridization colocalized expression to ACTH staining cells only. However, ACTH-R mRNA levels were undetectable in 16 of 22 ACTH-secreting tumors and in both silent corticotroph tumors. Diagnostic preoperative plasma ACTH levels were significantly lower in the ACTH-R positive ACTH-secreting tumors, compared with those who were ACTH-R negative (P = 0.0006). Direct sequencing of the coding region of the ACTH-R in cDNA from three ACTH-secreting tumors positively expressing the receptor showed no mutations, as did sequencing of genomic DNA in three receptor negative ACTH-secreting tumors and the two silent corticotrophs. These results provide further evidence compatible with an ACTH feedback loop in the pituitary and suggest that loss of expression of the ACTH-R in corticotroph adenomas of patients with Cushing's disease may play a role in the resistance to feedback of the pituitary-adrenal axis seen in these patients.

Adenoma↗