primerjalna analiza
Povzetek
Rak dojke je najpogosteje diagnosticiran rak in prizadene predvsem ženske. Največji izziv za zdravljenje predstavlja trojno negativni rak dojke (TNRD), ki je najbolj agresivna oblika te bolezni in za katero nimamo dobrih tarčnih zdravil. Poleg standardnih terapij bolnice pogosto posegajo tudi po alternativnih oblikah zdravljenja, še posebej je pogosta uporaba kanabinoidov, vendar je njihov vpliv na terapijo še neraziskan. V skupini dr. Fon Tacer so pred nedavnim ugotovili, da je protein γKlotho povišano izražen v skupini bolnic s TNRD in nujno potreben za preživetje rakavih celic in njihovo odpornost na kemoterapijo. Namen našega dela pa je bilo ugotoviti izražanje proteinov Klotho in kanabinoidnih receptorjev (CNR) pri raku dojke ter raziskati vpliv γKlotha in kanabinoidov na odziv na kemoterapijo. S pregledom javno dostopnih podatkovnih baz in z analizo PCR v realnem času smo določili izražanje mRNA proteinov Klotho in CNR v skupinah raka dojke in v različnih celičnih linijah. Nato smo celice, ki povišano izražajo γKlotho, tretirali s kemoterapevtikom doksorubicinom in kanabidiolom ter njuno kombinacijo. Potrdili smo, da so celice, ki izražajo γKlotho, v primerjavi s kontrolnimi celicami bolj odporne proti doksorubicinu. Nato smo pokazali, da tudi kanabidiol inhibira rast celic TNRD in poveča učinkovitost doksorubicina. Nazadnje pa smo ugotovili, da se na doksorubicin in kanabidiol podobno odzovejo celice tumorja mlečnih žlez pri psicah, ki imajo TNRD molekularne in histološke podobnosti s tumorji mlečnih žlez, ki so najpogostejša oblika tumorjev pri nesteriliziranih psicah. Naše predhodne raziskave tako dodatno nakazujejo, da predstavljajo zanimiv predklinični model za to agresivno obliko raka dojke.
Ključne besede
trojno negativni rak dojke;γKlotho;kanabinoidni receptorji;magistrska dela;
Podatki
Jezik: |
Slovenski jezik |
Leto izida: |
2022 |
Tipologija: |
2.09 - Magistrsko delo |
Organizacija: |
UL BF - Biotehniška fakulteta |
Založnik: |
[D. Herga] |
UDK: |
616-006 |
COBISS: |
128520963
|
Št. ogledov: |
36 |
Št. prenosov: |
4 |
Ocena: |
0 (0 glasov) |
Metapodatki: |
|
Ostali podatki
Sekundarni jezik: |
Angleški jezik |
Sekundarni naslov: |
ǂThe ǂrole of Klotho proteins and cannabinoid receptors in the response of cell therapy to triple-negative breast cancer and canine mammary tumors |
Sekundarni povzetek: |
Breast cancer is the most commonly diagnosed cancer that affects mainly women. Triple-negative breast cancer (TNBC) is the most aggressive type of this disease and remains a challenging problem, mainly due to the lack of targeted therapies. In addition to standard therapies, patients often resort to alternative forms of treatment, especially cannabinoids, but the impact of cannabinoids on the therapy is underexplored. Previous work in Dr. Fon Tacer’s lab shown that γKlotho protein is highly expressed in a subset of TNBC patients, required for TNBC cell survival and therapy resistance. With our work we aimed to investigate the impact of γKlotho and cannabinoids on the response to chemotherapy. First, we examined publicly available databases and performed real-time PCR analysis to determine mRNA expression of Klotho and CNR proteins in different breast cancer tumor types and cell lines. Next, we treated the cells that express γKlotho or control vector with chemotherapeutic doxorubicin and cannabidiol or their combination. We confirmed that cells expressing γKlotho are more resistant to doxorubicin treatment compared to control cells. Further, we showed that cannabidiol also inhibited growth of TNBC cells and importantly increased the efficacy of doxorubicin. Finally, we found that canine mammary tumor cells, which have molecular and histological similarities to TNBC and are the most common form of tumors in non-sterilized dogs, responded similarly to doxorubicin and cannabidiol. Our preliminary research thus further shows that they represent an interesting preclinical model for this aggressive form of breast cancer. |
Sekundarne ključne besede: |
triple negative breast cancer;γKlotho;cannabinoid receptors;master thesis;Rak dojke;Univerzitetna in visokošolska dela; |
Vrsta dela (COBISS): |
Magistrsko delo/naloga |
Študijski program: |
0 |
Konec prepovedi (OpenAIRE): |
1970-01-01 |
Komentar na gradivo: |
Univ. v Ljubljani, Biotehniška fak., Oddelek za biologijo |
Strani: |
1 spletni vir (1 datoteka PDF (XI, 56 str., [1] str. pril.)) |
ID: |
16888961 |