Publications (29) View all
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Article: Correlation between tumor-associated proteins and response to neoadjuvant treatment in patients with advanced squamous-cell esophageal cancer.
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ABSTRACT: Possible predictive markers of response to neoadjuvant radiochemotherapy (NRCT) of esophageal cancer have been identified. Patient biopsies were obtained from both tumor and normal tissue before the NRCT of locally advanced esophageal squamous cell carcinoma. Protein solutions were separated and immunoblot analysis was performed with heat shock protein (Hsp)16.2, heme-binding protein 2 (SOUL), BCL2-associated X protein (Bax), B-cell-associated leukemia protein 2 (Bcl-2) and heat shock protein 90 (Hsp90) antibodies. Following NRCT, the patients were restaged according to the Response Evaluation Criteria In Solid Tumors (RECIST). Following resections the pathological down-staging was evaluated. Clinical restaging revealed a response rate of 65%. Pathological examination revealed down-staging in 30% and 25% of the cases for the T and N categories respectively. Compared to the normal esophageal mucosa, a decreased expression of Hsp16.2, Hsp90 and SOUL proteins and an increased Bax/Bcl-2 ratio was found in the responding tumors. Hsp16,2, Hsp90 and SOUL expression and Bax/ Bcl-2 ratio correlates to the efficacy of NRCT and predict outcome in patients with locally advanced squamous-cell esophageal cancer.Anticancer research 05/2011; 31(5):1769-75. · 1.73 Impact Factor -
Article: [Modern 3D conformal craniospinal radiotherapy planning method].
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ABSTRACT: The main problem of craniospinal irradiation (CSI) is the matching of the fields. The use of a suitable technique is very important because matching of the fields is necessary to use for the optimal cancer irradiation of the long planning target volume (PTV). Since 2007, 8 patients have received CT-based, 3D-planned conformal CSI in our Institute. Patient immobilization was made in prone position in a vacuum bed, using skull and pelvis masks. Organ-at-risk (OAR) contours were made by radiographers. PTV was contoured by radiation oncologists. The prescribed dose to the PTV was 36 Gy with 1.8 Gy dose per fraction. In the planning process the following aspects were taken under consideration: all points of the PTV had to receive at least 95% of the prescribed dose (according to ICRU 50, 62); at junction field edges the overlapping parts were eliminated using a multisegmental technique, where the adjacent segment ends of the neighbouring fields were shifted two times 2 cm, so that the three equally weighted segments used in one field had 2-2 cm distance from each other. In the CSI planning the shape of the patient and so the length of the PTV has made a big emphasis on determining the number of field matching. Thus in some cases instead of two, only one field matching was sufficient - this could be achieved by increasing the source-to-skin distance (SSD) of the fields. The verification made with a solid-water phantom justified the precision of the field matching. The offset used at junction field edges in between one treatment facilitates the verification of field matching - and so the patient positioning. Thus the possibility of having overdosed regions could be reduced, which was very important from a radiation biological point of view.Magyar Onkológia 01/2011; 55(3):187-92. -
Article: TIP47 protects mitochondrial membrane integrity and inhibits oxidative-stress-induced cell death.
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ABSTRACT: We found that overexpression of tail interacting protein of 47kDa (TIP47), but not its truncated form (t-TIP47) protected NIH3T3 cells from hydrogen-peroxide-induced cell death, prevented the hydrogen-peroxide-induced mitochondrial depolarization determined by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolylcarbocyanine iodide (JC1), while suppression of TIP47 in HeLa cells facilitated oxidative-stress-induced cell death. TIP47 was located to the cytoplasm of untreated cells, but some was associated to mitochondria in oxidative stress. Recombinant TIP47, but not t-TIP47 increased the mitochondrial membrane potential (Deltapsi), and partially prevented Ca(2+) induced depolarization. It is assumed that TIP47 can bind to mitochondria in oxidative stress, and inhibit mitochondria mediated cell death by protecting mitochondrial membrane integrity.FEBS letters 05/2010; · 3.54 Impact Factor -
Article: Facilitation of mitochondrial outer and inner membrane permeabilization and cell death in oxidative stress by a novel Bcl-2 homology 3 domain protein.
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ABSTRACT: We identified a sequence homologous to the Bcl-2 homology 3 (BH3) domain of Bcl-2 proteins in SOUL. Tissues expressed the protein to different extents. It was predominantly located in the cytoplasm, although a fraction of SOUL was associated with the mitochondria that increased upon oxidative stress. Recombinant SOUL protein facilitated mitochondrial permeability transition and collapse of mitochondrial membrane potential (MMP) and facilitated the release of proapoptotic mitochondrial intermembrane proteins (PMIP) at low calcium and phosphate concentrations in a cyclosporine A-dependent manner in vitro in isolated mitochondria. Suppression of endogenous SOUL by diced small interfering RNA in HeLa cells increased their viability in oxidative stress. Overexpression of SOUL in NIH3T3 cells promoted hydrogen peroxide-induced cell death and stimulated the release of PMIP but did not enhance caspase-3 activation. Despite the release of PMIP, SOUL facilitated predominantly necrotic cell death, as revealed by annexin V and propidium iodide staining. This necrotic death could be the result of SOUL-facilitated collapse of MMP demonstrated by JC-1 fluorescence. Deletion of the putative BH3 domain sequence prevented all of these effects of SOUL. Suppression of cyclophilin D prevented these effects too, indicating that SOUL facilitated mitochondrial permeability transition in vivo. Overexpression of Bcl-2 and Bcl-x(L), which can counteract the mitochondria-permeabilizing effect of BH3 domain proteins, also prevented SOUL-facilitated collapse of MMP and cell death. These data indicate that SOUL can be a novel member of the BH3 domain-only proteins that cannot induce cell death alone but can facilitate both outer and inner mitochondrial membrane permeabilization and predominantly necrotic cell death in oxidative stress.Journal of Biological Chemistry 11/2009; 285(3):2140-51. · 4.77 Impact Factor -
Article: [Modern three-dimensional conformal craniospinal radiotherapy].
[show abstract] [hide abstract]
ABSTRACT: The main problem of craniospinal irradiation (CSI) is the matching of the fields. The use of a suitable technique is very important because matching of the fields is necessary to use for the optimal cancer irradiation of the long planning target volume (PTV). Since 2007, 8 patients have received CT-based, 3D-planned conformal CSI in our Institute. Patient immobilization was made in prone position in a vacuum bed, using skull and pelvis masks. Organ-at-risk (OAR) contours were made by radiographers. PTV was contoured by radiation oncologists. The prescribed dose to the PTV was 36 Gy with 1.8 Gy dose per fraction. In the planning process the following aspects were taken under consideration: all points of the PTV had to receive at least 95% of the prescribed dose (according to ICRU 50, 62); at junction field edges the overlapping parts were eliminated using a multisegmental technique, where the adjacent segment ends of the neighbouring fields were shifted two times 2 cm, so that the three equally weighted segments used in one field had 2-2 cm distance from each other. In the CSI planning the shape of the patient and so the length of the PTV has made a big emphasis on determining the number of field matching. Thus in some cases instead of two, only one field matching was sufficient - this could be achieved by increasing the source-to-skin distance (SSD) of the fields. The verification made with a solid-water phantom justified the precision of the field matching. The offset used at junction field edges in between one treatment facilitates the verification of field matching - and so the patient positioning. Thus the possibility of having overdosed regions could be reduced, which was very important from a radiation biological point of view.Magyar Onkológia 09/2011; 55(3):187-92.
