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171.
The development of nuclear medicine in Slovenia and Ljubljana; half a century of nuclear medicine in Slovenia
Zvonka 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: 101; Prenosov: 52
.pdf Celotno besedilo (552,70 KB)
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172.
Genetic polymorphisms in homologous recombination repair genes in healthy Slovenian population and their influence on DNA damage
Katja 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: 101; Prenosov: 30
.pdf Celotno besedilo (532,36 KB)

173.
Human tooth pulp anatomy visualization by 3D magnetic resonance microscopy
Dušan Šušterčič, Igor Serša, 2012, izvirni znanstveni članek

Povzetek: Background. Precise assessment of dental pulp anatomy is of an extreme importance for a successful endodontic treatment. As standard radiographs of teeth provide very limited information on dental pulp anatomy, more capable methods are highly appreciated. One of these is 3D magnetic resonance (MR) microscopy of which diagnostic capabilities in terms of a better dental pulp anatomy assessment were evaluated in the study. Materials and methods. Twenty extracted human teeth were scanned on a 2.35 T MRI system for MR microscopy using the 3D spin-echo method that enabled image acquisition with isotropic resolution of 100 m. The 3D images were then post processed by ImageJ program(NIH) to obtain advanced volume rendered views of dental pulps. Results. MR microscopy at 2.35 T provided accurate data on dental pulp anatomyin vitro. The data were presented as a sequence of thin 2D slices through the pulp in various orientations or as volume rendered 3D images reconstructed form arbitrary view-points. Sequential 2D images enabled only anapproximate assessment of the pulp, while volume rendered 3D images were more precise in visualization of pulp anatomy and clearly showed pulp diverticles, number of pulp canals and root canal anastomosis. Conclusions. This in vitro study demonstrated that MR microscopy could provide very accurate 3D visualization of dental pulp anatomy. A possible future application of the method in vivo may be of a great importance for the endodontic treatment.
Objavljeno v DiRROS: 21.03.2024; Ogledov: 111; Prenosov: 29
.pdf Celotno besedilo (1004,44 KB)

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Cathepsin X in serum from patients with colorectal cancer: relation to prognosis
Tjaša Vižin, Ib Jarle Christensen, Hans Jørgen Nielsen, Janko Kos, 2012, izvirni znanstveni članek

Povzetek: Background. Up-regulation of lysosomal cysteine protease cathepsin X (Cat X) is associated with disorders of the immune system and neurodegenerative diseases, while its role in the development and progression of cancer is less understood. Enhanced secretion of pro-Cat X was observed in malignant processes, and therefore, the level of total serum Cat X rather than the active enzyme may better reflect the tumour status. Patients and methods. Seventy-seven patients with colorectal cancer (CRC) were included in a retrospective study. Blood samples were collected prior to therapy. Using ELISA, the values of total Cat X were measured in serum. Groups of healthy persons (n=77), patients with adenomas (n=77) and patients with non-neoplastic findings (n=77) were included. Results. Significant differences between the group of colorectal patients and the groups of healthy persons, adenoma patients and patients with non-malignant findings could not be shown (p=0.89). Within the group of CRC, higher levels of total Cat X significantly correlated to shorter overall survival (HR=2.08, 95% CI:1.07-4.05, p=0.028). Conclusions. Total serum Cat X could be a useful prognostic indicator for determining survival of patients with CRC. Increased serum levels of total CatX may reflect more aggressive tumour cell phenotypes and suggest the involvement of Cat X in processes involved in later stages of tumour progression.
Ključne besede: cysteine cathepsins, cathepsin X, colorectal cancer, prognosis, serum biomarker
Objavljeno v DiRROS: 21.03.2024; Ogledov: 92; Prenosov: 56
.pdf Celotno besedilo (360,31 KB)
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176.
Assessment of the tumourigenic and metastatic properties of SK-MEL28 melanoma cells surviving electrochemotherapy with bleomycin
Vesna Todorović, Gregor Serša, Vid Mlakar, Damjan Glavač, Maja Čemažar, 2012, izvirni znanstveni članek

Povzetek: Background. Electrochemotherapy is a local treatment combining chemotherapy and electroporation and is highly effective treatment approach for subcutaneous tumours of various histologies. Contrary to surgery and radiation, the effect of electrochemotherapy on metastatic potential of tumour cells has not been extensively studied. The aim of the study was to evaluate the effect of electrochemotherapy with bleomycin on the metastatic potential of human melanoma cells in vitro. Materials and methods. Viable cells 48 hours after electrochemotherapy were tested for their ability to migrate and invade through Matrigel coated porous membrane. In addition, microarray analysis and quantitative Real-Time PCR were used to detect changes in gene expression after electrochemotherapy. Results. Cell migration and invasion were not changed in melanoma cells surviving electrochemotherapy.Interestingly, only a low number of tumourigenesis related genes was differentially expressed after electrochemotherapy. Conclusions. Our data suggest that metastatic potential of human melanoma cells is not affected by electrochemotherapy with bleomycin, confirming safe role of electrochemotherapy in the clinics.
Objavljeno v DiRROS: 21.03.2024; Ogledov: 308; Prenosov: 52
.pdf Celotno besedilo (640,99 KB)
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177.
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Effects of electrochemotherapy on immunologically important modifications in tumor cells
Urša Kešar, Boštjan Markelc, Tanja Jesenko, Katja Uršič Valentinuzzi, Maja Čemažar, Primož Strojan, Gregor Serša, 2023, izvirni znanstveni članek

Povzetek: Electrochemotherapy (ECT) is a clinically acknowledged method that combines the use of anticancer drugs and electrical pulses. Electrochemotherapy with bleomycin (BLM) can induce immunogenic cell death (ICD) in certain settings. However, whether this is ubiquitous over different cancer types and for other clinically relevant chemotherapeutics used with electrochemotherapy is unknown. Here, we evaluated in vitro in the B16-F10, 4T1 and CT26 murine tumor cell lines, the electrochemotherapy triggered changes in the ICD-associated damage-associated molecular patterns (DAMPs): Calreticulin (CRT), ATP, High Mobility Group Box 1 (HMGB1), and four immunologically important cellular markers: MHCI, MHC II, PD-L1 and CD40. The changes in these markers were investigated in time up to 48 h after ECT. We showed that electrochemotherapy with all three tested chemotherapeutics induced ICD-associated DAMPs, but the induced DAMP signature was cell line and chemotherapeutic concentration specific. Similarly, electrochemotherapy with CDDP, OXA or BLM modified the expression of MHC I, MHC II, PD-L1 and CD40. The potential of electrochemotherapy to change their expression was also cell line and chemotherapeutic concentration specific. Our results thus put the electrochemotherapy with clinically relevant chemotherapeutics CDDP, OXA and BLM on the map of ICD inducing therapies.
Ključne besede: electrochemotherapy, cisplatin, immune response
Objavljeno v DiRROS: 21.03.2024; Ogledov: 94; Prenosov: 51
.pdf Celotno besedilo (7,17 MB)
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179.
Gene immunotherapy of colon carcinoma with IL-2 and IL-12 using gene electrotransfer
Tilen Komel, Maša Omerzel, Urška Kamenšek, Katarina Žnidar, Urša Lampreht Tratar, Simona Kranjc Brezar, Klemen Dolinar, Sergej Pirkmajer, Gregor Serša, Maja Čemažar, 2023, izvirni znanstveni članek

Povzetek: Gene immunotherapy has become an important approach in the treatment of cancer. One example is the introduction of genes encoding immunostimulatory cytokines, such as interleukin 2 and interleukin 12, which stimulate immune cells in tumours. The aim of our study was to determine the effects of gene electrotransfer of plasmids encoding interleukin 2 and interleukin 12 individually and in combination in the CT26 murine colon carcinoma cell line in mice. In the in vitro experiment, the pulse protocol that resulted in the highest expression of IL-2 and IL-12 mRNA and proteins was used for the in vivo part. In vivo, tumour growth delay and also complete response were observed in the group treated with the plasmid combination. Compared to the control group, the highest levels of various immunostimulatory cytokines and increased immune infiltration were observed in the combination group. Long-term anti-tumour immunity was observed in the combination group after tumour re-challenge. In conclusion, our combination therapy efficiently eradicated CT26 colon carcinoma in mice and also generated strong anti-tumour immune memory.
Ključne besede: colon carcinoma, gene electrotransfer, gene immunotherapy
Objavljeno v DiRROS: 21.03.2024; Ogledov: 119; Prenosov: 55
.pdf Celotno besedilo (6,92 MB)
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180.
Breast cancer risk prediction using Tyrer-Cuzick algorithm with an 18-SNPs polygenic risk score in a European population with below-average breast cancer incidence
Tjaša Oblak, Petra Škerl, Benjamin J. Narang, Rok Blagus, Mateja Krajc, Srdjan Novaković, Janez Žgajnar, 2023, izvirni znanstveni članek

Povzetek: Goals: To determine whether an 18 single nucleotide polymorphisms (SNPs) polygenic risk score (PRS18) improves breast cancer (BC) risk prediction for women at above-average risk of BC, aged 40-49, in a Central European population with BC incidence below EU average. Methods: 502 women aged 40-49 years at the time of BC diagnosis completed a questionnaire on BC risk factors (as per Tyrer-Cuzick algorithm) with data known at age 40 and before BC diagnosis. Blood samples were collected for DNA isolation. 250 DNA samples from healthy women aged 50 served as a control cohort. 18 BC-associated SNPs were genotyped in both groups and PRS18 was calculated. The predictive power of PRS18 to detect BC was evaluated using a ROC curve. 10-year BC risk was calculated using the Tyrer-Cuzick algorithm adapted to the Slovenian incidence rate (S-IBIS): first based on questionnaire-based risk factors and, second, including PRS18. Results: The AUC for PRS18 was 0.613 (95 % CI 0.570-0.657). 83.3 % of women were classified at above-average risk for BC with S-IBIS without PRS18 and 80.7 % when PRS18 was included. Conclusion: BC risk prediction models and SNPs panels should not be automatically used in clinical practice in different populations without prior population-based validation. In our population the addition of an 18SNPs PRS to questionnaire-based risk factors in the Tyrer-Cuzick algorithm in general did not improve BC risk stratification, however, some improvements were observed at higher BC risk scores and could be valuable in distinguishing women at intermediate and high risk of BC.
Ključne besede: early breast cancer, polygenic risk score, risk prediction
Objavljeno v DiRROS: 21.03.2024; Ogledov: 113; Prenosov: 32
.pdf Celotno besedilo (1,54 MB)

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