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Rak dojke je z nekaj več kot 1000 novimi bolnicami na leto na prvem mestu po številu obolelih žensk za rakastimi boleznimi v Sloveniji. številka vključuje sporadične in dedne oblike raka na dojki. Dedne oblike raka na dojki so najpogosteje povezane z mutacijami v genih BRCA1 in BRCA2, zato se številni strokovnjaki s tega področja zavzemajo za genetsko testiranje bolnikov, pri katerih obstaja sum na dedno obliko bolezni. Testiranje bolnic/-kov in njihovih sorodnikov je dokaj težavno zaradi zahtevnosti metod genetskega testiranja, stroškov testiranja ter nezadostnega poznavanja in predvidevanja vseh možnih vplivov dokazane mutacije pri nastanku raka na dojki. V tem delu predstavljamo osnovne metodološke podatke za odkrivanje petih različnih mutacij v genu BRCA1 pri bolnicah/-kih s karcinomom dojke in njihovih sorodnikih. Mutacije 1806C>T, 300T>G, 300T>A, 310G>A, 5382insC določamo s polimerazno verižno reakcijo (PCR) v realnem času in analizo talitvene krivulje. Primerjava z neposrednim sekveniranjem je pokazala, da je uporabljena metoda dovolj občutljiva in hitra za dnevno rutinsko določanje mutacij v DNA, izolirani iz periferne krvi.

Mutacija V600E predstavlja več kot 90 % vseh opisanih mutacij v genu BRAF pri različnih vrstah tumorjev. Protein, ki nastane kot produkt onkogena BRAF z mutacijo V600E (BrafV600E), sproža nenehno signaliziranje prek signalne poti RAS-RAF-MAPK, kar povzroči številnejše delitve celice in njeno maligno transformacijo. Zato ima onkogen BrafV600E pomembno vlogo pri indukciji in napredovanju tumorja ter verjetno predstavlja zgodnji dogodek v procesu maligne transformacije. Po podatkih iz literature je čezmerno izražen v različnih vrstah solidnih tumorjev, kot so melanom, metastatski rak debelega črevesa in danke, papilarni rak ščitnice, rak ledvic (RCC), hepatocelularni karcinom (HCC), velikocelični rak pljuč (NSCLC) in serozni rak jajčnikov. Na Oddelku za molekularno diagnostiko smo uvedli metodo za določanje mutacije V600E v genu BRAF. Metoda temelji na PCR-pomnoževanju in uporabi specifičnih sond. Izkazala se je kot primerna za rutinsko diagnostiko. V primerjavi z neposrednim sekveniranjem, ki velja za zlati standard, sta bili njeni občutljivost in specifičnost 100-odstotni. Zaradi velike specifičnosti je zanesljiva za ločevanje med normalnim in mutiranim genotipom BRAF in je primerna za hitro rutinsko diagnostiko. The most common BRAF mutation, which accounts for more than 90% of all BRAF mutations described in different malignancies, is a glutamic acid for valin substitution at position 600 (V600E). BRAF gene carrying V600E mutation is termed BrafV600E oncogene. The product of BrafV600E is a protein which induces constitutive signaling in cells through hyperactivation of the RAS-RAF-MAPK pathway leading finally to increased cellular proliferation and malignant transformation. BrafV600E oncogene thus plays an important role in cancer induction and progression and is probably mutated early in the process of malignant transformation. According to the literature, BrafV600E oncogene is over-expressed in diverse human solid tumors: melanoma, colorectal carcinoma, papillary thyroid carcinoma, renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC) and serous ovarian cancer. At the Department of Molecular Diagnostics, we introduced a method for the detection of V600E mutation in BRAF gene based on real-time PCR and on application of specific probes. The method is robust and convenient for routine diagnostics. Its sensitivity and specificity when determined in comparison to the results of direct sequencing are as high as 100%. Due to the high specificity, the method allows the discrimination between normal and mutated BRAF genotypes and is therefore suitable for fast and accurate routine diagnostics.

Gensko testiranje za dedno obliko malignega melanoma kože na OI Ljubljana opravljamo od leta 2005. Izbor bolnikov za testiranje poteka v okviru genetskega svetovanja. Testiramo bolnike in njihove zdrave sorodnike, če sta v družini najmanj dva obolela člana, in bolnike s primarnimi multiplimi melanomi brez obremenjujoče družinske anamneze. Na oddelku za molekularno diagnostiko z metodo sekvenčne analize iščemo in določamo neznane točkovne mutacije ter manjše delecije in insercije v eksonih genov, povezanih z nastankom malignega melanoma kože: CDKN2A, CDK4 in MC1R. Do sedaj smo testirali 70 oseb: 40 bolnikov in njihovih zdravih sorodnikov iz 28 različnih družin, obremenjenih z družinsko anamnezo, ter 30 bolnikov s primarnimi multiplimi melanomi. Sekvenčna analiza genov, povezanih z dedno obliko malignega melanoma kože, je pokazala, da so mutacije CDKN2A p16INK4a pri bolnikih z družinsko anamnezo zelo pogoste (37,5 %). Mutacij CDKN2A p14ARF in CDK4 pri slovenskih bolnikih nismo našli. At the Institute of Oncology Ljubljana, Department of Molecular Diagnostics, genetic testing for familial cutaneous melanoma (CM) was started in 2005. The patients are selected according to the guidelines of genetic counseling for CM. The screening for melanoma susceptibility genes is performed in the patients and their healthy relatives from the families with at least two affected family members and in the patients with multiple primary CM without family history. The mutation screening for melanoma susceptibility genes – CDKN2A, CDK4 and MC1R is performed by direct sequencing. Altogether 70 patients and their healthy relatives (40 patients or their relatives selected from 28 families after considering their on family history and 30 patients with multiple primary CM) have been tested so far. Our results showed high prevalence of CDKN2A p16INK4a mutations in the patients with familial CM. In CDKN2A p14ARF and CDK4, no mutations were detected in Slovenian patients.

Vsaka organizacija je del širšega okolja in kot takšna se ne more izogniti komunikaciji z različnimi javnostmi. Med pomembne javnosti sodijo mediji oz. medijske hiše, ki imajo v okolju dvojno vlogo: širši javnosti v obliki novinarskih prispevkov posredujejo informacije o podjetjih, poleg tega s podjetji na različne načine poslovno sodelujejo, saj so tudi medijske hiše podjetja. Mediji so pomembni (so)ustvarjalci javnega mnenja, zato si podjetja prizadevajo, da bi bila prisotna v medijih in bi jim bili novinarski prispevki naklonjeni. Količina, obseg in naklonjenost medijskih objav podjetju niso odvisni izključno od medijev in njihovih novinarjev, pač pa tudi od podjetja in njegove kakovosti upravljanja odnosov z mediji. Za učinkovito upravljanje odnosov z mediji je bistvenega pomena razumevanje odnosa med podjetjem in novinarji, kar smo raziskovali tudi v našem delu. Da smo področje podrobneje spoznali, smo pregledali aktualno literaturo z relevantnih področij ter na njeni osnovi umestili odnose z mediji v širši teoretični okvir integriranega trženjskega komuniciranja, predstavili smo delovanje in značilnosti medijev oz. medijskih hiš s poudarkom stanja na tem področju v Sloveniji ter povzeli ključna določila zakonov in etičnih kodeksov z relevantnih področij, to je medijev, novinarstva in oglaševanja. V empiričnem delu smo najprej opravili globinski intervju z novinarjem, nato pa še kvantitativno raziskavo, za katero smo s pomočjo spletne ankete pridobili odgovore 65 novinarjev in 106 predstavnikov podjetij. Ključno raziskovalno vprašanje je bilo, ali področje odnosov z mediji razumejo predstavniki podjetij drugače kot novinarji. Ugotovili smo, da predstavniki podjetij pripisujejo medsebojnemu sodelovanju z novinarji precej večji pomen kot novinarji. Novinarji celo to sodelovanje ocenjujejo na intervalu med nevtralnim in nepomembnim, medtem ko ga predstavniki podjetij ocenjujejo na intervalu med nevtralnim in pomembnim. Tako novinarji kot tudi predstavniki za odnose z mediji se ne strinjajo, da bi bil t. i. PR slovenskih podjetij na zelo visoki ravni, pri čemer je nestrinjanje med novinarji še nekoliko močnejše kot med predstavniki podjetij. Ugotovili smo tudi, da med podjetji, ki bolje razumejo delovanje medijev, in podjetji, ki slabše razumejo delovanje medijev, obstajajo razlike pri presoji uporabnosti informacij za medije, saj podjetja, ki bolje razumejo delovanje medijev, večinoma tudi bolje presojajo uporabnost informacij za medije kot podjetja, ki slabše razumejo delovanje medijev. Za dolgoročno dobre odnose med dvema skupinama je vedno najprej potrebno vzajemno razumevanje, ki pa v osnovi vedno izhaja iz poznavanja nasprotnega področja, zato predlagamo, da bi imelo vsako podjetje osebo, ki bi skrbela za odnose z mediji. Medijem bi samoiniciativno sporočala pomembne novosti o dogajanju v njihovem podjetju, hkrati pa bi se zavedala, da novinarje priganja rok oddaje in bi jim zato pravočasno zagotavljala potrebne informacije in sogovornike. Every organization is a part of the broader environment and cannot avoid to communicate with different publics. One of the important publics are the media and media organizations, which have a dual role in the environment: the first is that journalism provides information about the companies through the articles to the general public and the second is that the media organizations are companies, which in different ways cooperate with other companies. The media are important as the creators of public opinion and this is the main reason why companies want to be present in the media coverage and that the articles are written in their favor. The amount, scope and affection of media coverage do not depend only on the media and their journalists, but also on the company and its quality of the management of media relations. Understanding the relationship between the company and the journalists is essential in order to effectively manage this relationship. To get a better insight into the field, we reviewed the relevant current literature and placed the media relations into a broader theoretical framework of integrated marketing communications. Further we presented the performance and characteristics of the media and media organizations focusing the situation in Slovenia and summarized the key provisions of the laws and ethical codes of relevant areas, which are the media, journalism and advertising. In the empirical part, we have conducted an in-depth interview with a journalist, followed by quantitative research, for which we used an online questionnaire and received responses of 65 journalists and 106 representatives of companies. The main research question was whether the field of media relations is differently understood by the representatives of companies and the journalists. We found out that the company representatives find the cooperation between journalists and the company representatives more important than the journalists. Even more, journalists rate this cooperation in the interval between neutral and insignificant, while company representatives rate it in the interval between neutral and important. The journalists as well as the representatives of media relations do not agree that the so-called PR of Slovenian companies is at a very high level, although the disagreement among journalists is still slightly stronger than among company representatives. Besides, we have found, that the differences exist in assessing the usefulness of the information for the media between the companies that better understand the functioning of the media to those that understand it poorly. The companies that understand the functioning of the media better also assess the usefulness of the information better. To gain a long-term relationship between the two groups a mutual understanding is essential. But this understanding is always based on the knowledge of the opposite field. Therefore we suggest that every company should have a person responsible for media relations and to communicate important news about their company to the media. This person should also be aware of the fact that journalists are under pressure of their newsrooms, therefore they should gain the necessary information and contacts as soon as possible.

Na Oddelku za molekularno diagnostiko smo na področju diagnostike limfomov uvedli dodatno metodo za določanje klonalnosti limfoidnih proliferacij. Tudi nova metoda temelji na verižni reakciji s polimerazo (PCR) in na uporabi različnih konsenzusnih oligonukleotidnih začetnikov. Metoda je validirana in registrirana za diagnostične potrebe (oznaka CE). Z razširjenim naborom oligonukleotidnih začetnikov in uporabo večjega števila začetnikov smo, po naših izračunih, izboljšali občutljivost določanja klonalnosti limfocitov B za 23,1 %, določanje klonalnosti limfocitov T pa za 14,3 %. Teoretično lahko sedaj z obema metodama določimo monoklonalno populacijo limfocitov pri 84,6 % B- in 85,7 % T-limfomov At the Department of Molecular Diagnostics, a new method for determining lymphoid proliferation clonality has been introduced in lymphoma diagnostics. The method is based on PCR and on the use of various consensus primers. It is validated and registered for the use in clinical diagnostics (CE-marked method). Our measurements confirmed that the use of extended number of primers improved the sensitivity of determining the lymphoid clonality of B-lymphocytes and T-lymphocytes by 23.1% and 14.3%, respectively. Both methods may, theoretically, be used in determining monoclonal population of lymphocytes in 84.6% of B- and 85.8 of T-lymphomas.