591. Staurosporine induces different cell death forms in cultured rat astrocytesJanez Šimenc, Metoda Lipnik-Štangelj, 2012, izvirni znanstveni članek Povzetek: 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.
Objavljeno v DiRROS: 22.03.2024; Ogledov: 156; Prenosov: 44
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592. 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, izvirni znanstveni članek Povzetek: 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.
Objavljeno v DiRROS: 22.03.2024; Ogledov: 405; Prenosov: 422
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593. 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, izvirni znanstveni članek Povzetek: 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)
Ključne besede: pljuča, rak (medicina), drobnocelični rak, metastaze, možgani
Objavljeno v DiRROS: 22.03.2024; Ogledov: 174; Prenosov: 48
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594. The development of nuclear medicine in Slovenia and Ljubljana; half a century of nuclear medicine in SloveniaZvonka Zupanič Slavec, Simona Gaberšček, Ksenija Slavec, 2012, pregledni znanstveni članek Povzetek: 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.
Objavljeno v DiRROS: 22.03.2024; Ogledov: 176; Prenosov: 93
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595. 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, izvirni znanstveni članek Povzetek: 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.
Objavljeno v DiRROS: 22.03.2024; Ogledov: 185; Prenosov: 41
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