Souvislost rozložení genové exprese jednotlivých typů somatostatinových receptorů SSTR1-SSTR5 a odpovědi pacientů s neuroendokrinními tumory na léčbu somatostatinovými analogy.

Title in English Association of gene expression profiles of somatostatin receptors SSTR1-SSTR5 with clinical response to somatostatin analogs treatment in patients witn neuroendocrine tumors.
Authors

SLABÝ Ondřej ŠACHLOVÁ Milana BEDNAŘÍKOVÁ Markéta FABIAN Pavel VYTOPILOVÁ Simona NENUTIL Rudolf VYZULA Rostislav

Year of publication 2008
Type Article in Proceedings
Conference Sborník abstrakt IV. DNY DIAGNOSTICKÉ, PREDIKTIVNÍ A EXPERIMENTÁLNÍ ONKOLOGIE (supplementum časopisu Onkologie)
MU Faculty or unit

Faculty of Medicine

Citation
Field Oncology and hematology
Keywords neuroendocrine tumors; somatostine analogs; prediction; somatostatin receptors
Description Somatostatin is a polypeptide hormone acting as an inhibitor of pituitary, pancreatic and gastrointestinal secretions. Somatostatinových analog is so successfully used in clinical practice for treating patients with hormonal hypersecretion associated with the development of neuroendocrine tumors (NET). Effect of somatostatin and also its analogue (SA) is mainly influenced by the type of receptor through which it is carried out. For somatostin so far identified five types of specific membrane receptors SSTR1 to SSTR5. Genes for different types of receptors are located on different chromosomes, suggesting not only the individual transcriptional control of each of them, but also their different functionality. Recent work has shown that agonizace each of these receptors is indeed associated with activation of different signaling pathways and different cellular responses. SSTR2 and SSTR5 are involved primarily in regulating the release of somatotropin, SSTR5 in addition regulates the secretion of insulin and glucagon. Far more interesting is the fact that the occupation and to a lesser extent SSTR3 SSTR2 a specific ligand can lead to induction of apoptosis. From the foregoing it can be assumed that the distribution of different types somatostatinových receptors, particularly in terms of increased expression of SSTR2 and SSTR3, can explain, and before the start of treatment and predict a better therapeutic response and still unsatisfactorily explained biologicky anti-neoplastic effect somatostatinových u some analog patients with NET. In our study, we decided to determine the mRNA levels for all five types of receptors somatostatinových using Real-Time PCR on a set of 25 patients with NET expressed hyperserkrecí hormone treated (n = 19 - octreotide, n = 6 - lanreotide) and followed up at the Masaryk Memorial Cancer Institute at Brno. Response was evaluated after six months of treatment, both at the biochemical (decrease or stabilization of serum chromogranin A and 5-HIOK in urine in 80% of cases), symptomatic (expressed effect on symptoms observed in 83% of cases) and radiology - in effect measurable lesions (in 48% objective response was observed - SD, PR, CR). Median analogues therapy to date is 14 months. The results of our study focused on the influence of the distribution of expression of different types of receptors on somatostatinových radiological response and survival parameters in patients treated with NET SA will be presented in our communication. Acknowledgements: This work was supported by research plan MZ0MOU2005.

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