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1542. Early outcome in endoscopic extended endonasal approach for removal of supradiaphragmatic craniopharyngiomas : a case series and a comprehensive reviewRoman Bošnjak, Mitja Benedičič, Alenka Vittori, 2013, original scientific article Abstract: Background. The choice of endoscopic expanded endonasal approach introduces the possibility of improved gross total resection of craniopharyngioma while minimizing surgical morbidity in a significant subset of patients. Methods. From our trans-sphenoidal surgical series of 331 cases, we retrospectively reviewed visual, endocrine and neuro-cognitive outcomes in the first consecutive eight patients (median age 63 years; range 4773 years) with newly diagnosed supradiaphragmatic craniopharyngioma (median tumour height 23 mm; range 1534 mm), removed by expanded endonasal approach (median follow-up 27 months; range 1069 months). Gross total resection was attempted in all patients. Results. Gross total resection was achieved in 6 of 8 patients. Visual improvement was present in 6 of 8 patients of patients or in 14 of 16 eyes. New endocrinopathy, including diabetes insipidus, appeared in 5 of 8 patients. Stalk was preserved in 4 patients. Cognitive decline was present in 2 cases. Five of 8 patients retained previous quality of life. Conclusions. Our early outcome results are comparable to the recent few expanded endonasal approach series, except for the incidence of new endocrinopathy and cerebrospinal fluid leak rate. This was influenced by higher number of transinfundibular tumours in our series, where stalk preservation is less likely, and not using nasoseptal flap or gasket closure in the first half of cases. Including data from the literature and ours, expanded endonasal approach shows a trend for improved gross total resection rate with less morbidity, more obviously for visual outcome and quality of life than for endocrine outcome. However, validity of expanded endonasal approach should be confirmed in a larger number of patients with a longer follow-up period. Published in DiRROS: 22.03.2024; Views: 265; Downloads: 93
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1543. Angiogenin and vascular endothelial growth factor expression in lungs of lung cancer patientsAleš Rozman, Mira Šilar, Mitja Košnik, 2012, original scientific article Abstract: Background. Lung cancer is the leading cause of cancer deaths. Angiogenesis iscrucial process in cancer growth and progression. This prospective study evaluated expression of two central regulatory molecules: angiogenin and vascular endothelial growth factor (VEGF) in patients with lung cancer. Patients and methods. Clinical data, blood samples and broncho-alveolar lavage(BAL) from 23 patients with primary lung carcinoma were collected. BAL fluid was taken from part of the lung with malignancy, and from corresponding healthy side of the lung. VEGF and angiogenin concentrations were analysed by an enzyme-linked immunosorbent assay. Dilution of bronchial secretions in the BAL fluid was calculated from urea concentration ratio between serum and BAL fluid. Results. We found no statistical correlation between angiogenin concentrations in serum and in bronchial secretions from both parts of the lung. VEGF concentrations were greater in bronchial secretions in the affectedside of the lung than on healthy side. Both concentrations were greater than serum VEGF concentration. VEGF concentration in serum was in positive correlation with tumour size (p = 0,003) and with metastatic stage ofdisease (p = 0,041). There was correlation between VEGF and angiogenin concentrations in bronchial secretions from healthy side of the lung and between VEGF and angiogenin concentrations in bronchial secretions from part of the lung with malignancy. Conclusion. Angiogenin and VEGF concentrations insystemic, background and local samples of patients with lung cancer are affected by different mechanisms. Pro-angiogenic activity of lung cancer has an important influence on the levels of angiogenin and VEGF. Published in DiRROS: 22.03.2024; Views: 360; Downloads: 104
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1544. Contrasting effect of recombinant human erythropoietin on breast cancer cell response to cisplatin induced cytotoxicityNina Trošt, Peter Juvan, Gregor Serša, Nataša Debeljak, 2012, original scientific article Abstract: Background. Human recombinant erythropoietin (rHuEpo) that is used for the treatment of the chemotherapy-induced anaemia in cancer patients was shown to cause detrimental effects on the course of disease due to increased adverse events inflicting patient's survival, potentially related to rHuEpo-induced cancer progression. In this study, we elucidate the effect of rHuEpo administration on breast cancer cell proliferation and gene expression after cisplatin (cDDP) induced cytotoxicity. Materials and methods. Two breast carcinoma models, MCF-7 and MDA-MB-231 cell lines, were used differing in oestrogen (ER) and progesterone (PR) receptors and p53 status. Cells wer e cultured with or without rHuEpo for 24 h or 9 weeks and their growth characteristics after cDDP treatment were assessed together with expression ofgenes involved in the p53-signaling pathway. Results. Short-term exposure ofbreast cancer cells to rHuEpo lowers their proliferation and reduces cDDP cytotoxic potency. In contrast, long-term exposure of MCF-7 cells to rHuEpo increases proliferation and predisposes MCF-7 cells to cDDP cytotoxicity, but has no effect on MDA-MB-231 cells. MDA-MB-231 cells show altered level of ERK phosphorylation, indicating involvement of MAPK signalling pathway. Gene expression analysis of p53-dependent genes and bcl-2 gene family members confirmed differences between long and short-term rHuEpo effects, indicating the most prominent changes in BCL2 and BAD expression. Conclusions. Proliferation and survival characteristics of MCF-7 cells are reversely modulated by the length of the rHuEpo exposure. On the other hand, MDA-MB-231 cells are almost irresponsive to long-term rHuEpo, supposedly due to the mutated p53 and ER(+)/PR(-) status. The p53 and ER/PR status may predict tumour response on rHuEpo and cDDP treatment. Keywords: breast cancer, erythropoietin, cisplatin, cytotoxicity Published in DiRROS: 22.03.2024; Views: 312; Downloads: 92
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1545. Staurosporine induces different cell death forms in cultured rat astrocytesJanez Šimenc, Metoda Lipnik-Štangelj, 2012, original scientific article Abstract: Background. Astroglial cells are frequently involved in malignant transformation. Besides apoptosis, necroptosis, a different form of regulated cell death, seems to be related with glioblastoma genesis, proliferation, angiogenesis and invasion. In the present work we elucidated mechanisms of necroptosis in cultured astrocytes, and compared them with apoptosis, caused by staurosporine. Materials and methods. Cultured rat cortical astrocytes wereused for a cell death studies. Cell death was induced by different concentrations of staurosporine, and modified by inhibitors of apoptosis (z-vad-fmk) and necroptosis (nec-1). Different forms of a cell death were detected using flow cytometry.Results. We showed that staurosporine, dependingon concentration, induces both, apoptosis as well as necroptosis.Treatment with 10-7 M staurosporine increased apoptosis of astrocytes after the regeneration in a staurosporine free medium. When caspases were inhibited, apoptosis was attenuated, while necroptosis was slightly increased. Treatment with 10-6 M staurosporine induced necroptosis that occurred after the regeneration of astrocytes in a staurosporine free medium, as well as without regeneration period. Necroptosis was significantly attenuated by nec-1 which inhibits RIP1 kinase. On the other hand, the inhibition of caspases had no effect on necroptosis. Furthermore, staurosporine activated RIP1 kinase increased the production of reactive oxygen species, while an antioxidant BHA significantly attenuated necroptosis.Conclusion. Staurosporine can induce apoptosis and/or necroptosis in cultured astrocytes via different signalling pathways. Distinction between different forms of cell death is crucial in the studies of therapy-induced necroptosis. Published in DiRROS: 22.03.2024; Views: 262; Downloads: 75
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1546. Lower tumour burden and better overall survival in melanoma patients with regional lymph node metastases and negative preoperative ultrasoundGašper Pilko, Janez Žgajnar, Maja Marolt-Mušič, Marko Hočevar, 2012, original scientific article Abstract: Background. The purpose of the study was to evaluate the ability of ultrasound(US) and fine needle aspiration biopsy (FNAB) in reducing the numberof melanoma patients requiring a sentinel node biopsy (SNB); to compare the amount of metastatic disease in regional lymph nodes in SNB candidates with clinically uninvolved lymph nodes and of those with US uninvolved lymph nodes; and to compare the overall survival (OS) of both groups. Methods. Between 2000 and 2007, a SNB was successfully performed in 707 patients with melanoma. The preoperative US of the regional lymph node basins was performed in 405 SNB candidates. In 14 of these patients, the US-guided FNAB was positive and they proceeded directly to lymph node dissection. In 391 patients, the preoperative US was either negative (343 patients) or suspicious(48 patients) (US group). In the remaining 316 patients the preoperative US was not performed (non-US group). Results. The proportion of macrometastatic sentinel lymph nodes (SN), number of metastatic lymph nodes per patient and proportion of nonsentinel lymph node metastases were found to be lower in the US group compared to the non-US group. The smaller tumour burden of the US group was reflected in a significantly better OS of patients with SN metastases. Conclusions. The preoperative US of regional lymph nodes spares some patients with melanoma from undergoing a SNB. Patients with regional metastases and a negative preoperative US have a significantly lower tumour burden in comparison to those with clinically negative lymph nodes, which is also reflected in a better OS. Published in DiRROS: 22.03.2024; Views: 535; Downloads: 469
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1547. Outcome of small cell lung cancer (SCLC) patients with brain metastases in a routine clinical settingMirko Lekić, Viljem Kovač, Nadja Triller, Lea Knez, Aleksander Sadikov, Tanja Čufer, 2012, original scientific article Abstract: Background. Small cell lung cancer (SCLC) represents approximately 13 tomediansurvival of SCLC patients treated by specific therapy (chemotherapy andžor radiotherapy) with regard to the 18%months in patients treated with standard chemotherapy and radiotherapy. Inpresence or absence of brain metastases at the time of diagnosis. Patients and methods. All SCLC patients have been treated in a routine clinical practice and followed up at theUniversity Clinic Golnik in Slovenia. In the retrospective study the medical files from 2002 to 2007 were review. All patients with cytological or histological confirmed disease and eligible for specific oncological treatment were included in the study. They have been treated according to the guidelines valid at the time. Chemotherapy and regular followed-up were carried out at the University Clinic Golnik and radiotherapy at the Institute of Oncology Ljubljana. Results. We found 251 patients eligible for the study. The median age of them was 65 years, majoritywere male (67%), smokers or ex-smokers (98%), with performance status 0 to 1 (83%). At the time of diagnosis no metastases were found in 64 patients(25.5%) and metastases outside the brain were presented in 153 (61.0%). Brain metastases, confirmedby a CT scan, were present in 34 patients (13.5%), most of them had also metastases at other localisations. (Abstract truncated at 2000 characters) Keywords: pljuča, rak (medicina), drobnocelični rak, metastaze, možgani Published in DiRROS: 22.03.2024; Views: 294; Downloads: 105
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1548. The development of nuclear medicine in Slovenia and Ljubljana; half a century of nuclear medicine in SloveniaZvonka Zupanič Slavec, Simona Gaberšček, Ksenija Slavec, 2012, review article Abstract: Background. Nuclear medicine began to be developed in the USA after 1938 when radionuclides were introduced into medicine and in Europe after radionuclides began to be produced at the Harwell reactor (England, 1947). Slovenia began its first investigations in the 1950s. This article describes the development of nucleor medicine in Slovenia and Ljubljana. The first nuclear medicine interventions were performed in Slovenia at the Internal Clinic in Ljubljana in the period 1954-1959. ln 1954, Dr Jože Satler started using radioactive iodine for thyroid investigations. In the same year, Dr Bojan Varl, who is considered the pioneer of nuclear medicine in Slovenia, began systematically introducing nuclear medicine. The first radioisotope laboratories were established in January 1960 at the Institute of Oncology and at the Internal Clinic. Under the direction of Dr. Varl, the laboratory at the Internal Clinicdeveloped gradually and in 1973 became the Clinic for Nuclear Medicine with departments for in viva and in vi/ro diagnostics and for the treatment ofinpatients and outpatients at the thyroid department. The Clinic for NuclearMedicine beca me a teaching unit of the Medical Faculty and developed its own post-graduate programme- the first student enrolled in 1972. In the 1960s, radioisotope laboratories opened in the general hospitals of Slovenj Gradec and Celje, and in the I 970s also in Maribor. Izola and Šempeter pri Novi Gorici. Conclusions. Nowadays, nuclear medicine units are modernly equipped and the staff is trained in morphological, functional and laboratory diagnostics in c1inical medicine. They also work on the treatment of cancer, increased thyroid function and other diseases. Published in DiRROS: 22.03.2024; Views: 297; Downloads: 171
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1549. Genetic polymorphisms in homologous recombination repair genes in healthy Slovenian population and their influence on DNA damageKatja Goričar, Nina Erčulj, Maja Zadel, Vita Dolžan, 2012, original scientific article Abstract: Background. Homologous recombination (HR) repair is an important mechanism involved in repairing double-strand breaks in DNA and for maintaining genomic stability. Polymorphisms in genes coding for enzymes involved in this pathway may influence the ca pa city for DNA repair. The aim of this study was to select tag single nucleotide polymorphisms (SNPs) in specific genes involved in HR repair, to determine their allele frequencies in a healthy Slovenian population and their influence on DNA damage detected with comet assay. Materials and methods. In total 373 individuals were genotyped for nine tag SNPs in three genes: XRCC3 722C>T, XRCC3 -316A>G, RAD51 -98G>C, RAD51 -61G>T, RAD51 1 522T>G, NBS1 553G>C, NBS1 1197A>G, NBS1 37117C>T and NBS1 3474A>C using competitive allele-specific amplification (KASPar assay). Comet assay was performed in a subgroup of 26 individuals to determine the influence of selected SNPs on DNA damage. Results. We observed that age significantly affected genotype frequencies distribution of XRCC3 -316A>G (P = 0.039) in healthy male blood donors. XRCC3 722C>T (P = 0.005), RAD51 -61G>T IP = 0.023) and NBS1 553G>C (P = 0.008) had a statistically significant influence on DNA damage. Conclusions. XRCC3 722C> T, RAD51 -61 G> T and NBS 1 553G>C polymorphisms significantly affect the repa ir of damaged DNA and may be of clinical importance as they are common in Slovenian population. Published in DiRROS: 22.03.2024; Views: 304; Downloads: 111
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