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Vloga melanomskih antigenov (MAGE) in kanabinoidnih receptorjev pri razvoju bolezni in odzivu na terapijo v celicah hormonsko odvisnega raka dojk
ID Tavčar Kunstič, Tajda (Author), ID Fon Tacer, Klementina (Mentor) More about this mentor... This link opens in a new window, ID Debeljak, Nataša (Co-mentor)

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Abstract
Rak dojke je najpogosteje diagnosticiran rak in poglavitni vzrok smrti zaradi raka pri ženskah po vsem svetu. Prognoza bolezni in odzivi bolnic na različne vrste zdravljenja se razlikujejo v različnih podskupinah te heterogene bolezni. Podskupine temeljijo na histoloških in molekularnih značilnostih tumorja, zlasti na izražanju estrogenskega in progesteronskega receptorja ter človeškega receptorja za epidermalni rastni dejavnik 2. Hormonsko odvisni rak dojke (HORD) je najpogostejša vrsta raka dojke. Izražanje melanomskih antigenov (MAGE) je povezano s slabšo klinično prognozo in odpornostjo na zdravljenje pri številnih vrstah raka, vključno z rakom dojke, vendar njihova vloga pri HORD ni preučena. Na odziv na zdravljenje bolnic s HORD lahko vpliva tudi sočasna uporaba alternativnega zdravljenja, npr. uporaba kanabinoidov. Kanabinoidi vplivajo na delovanje endogenih estrogenov, vendar je še vedno slabo znano, kako vplivajo na zdravljenje raka dojke. Namen našega dela je z bioinformatskimi analizami podatkovnih baz in analizo izražanja genov s kvantitativno reakcijo s polimerazo, sklopljeno z obratno transkripcijo, določiti izražanje hormonskih receptorjev, kanabinoidnih receptorjev in proteinov MAGE v celicah HORD. Preverili smo odziv celic HORD na terapijo z doksorubicinom, kanabidiolom, tamoksifenom in estradiolom. Z raziskavami smo pokazali izražanje nekaterih proteinov MAGE in kanabinoidnih receptorjev v celičnih linijah hormonsko odvisnega raka dojke. Ugotovili smo, da so se celice HORD bolje odzvale na kemoterapijo kot celice trojno negativnega raka dojke, po pričakovanjih pa se bolje odzivajo tudi na hormonsko terapijo. Zanimivo je, da se celična linija HORD MCF7 bolje odzvala na kombinacijo hormonske terapije s tamoksifenom in kanabidiolom, kar nakazuje, da bi morda bolnice s HORD lahko imele koristi od alternativne terapije s kanabidiolom kot dodatkom k hormonski terapiji. Potrebne pa so še nadaljnje raziskave.

Language:Slovenian
Keywords:Hormonsko odvisni rak dojke, MAGE, kanabinoidni receptorji
Work type:Master's thesis/paper
Typology:2.09 - Master's Thesis
Organization:BF - Biotechnical Faculty
Publisher:[T. Tavčar Kunstič ]
Year:2023
PID:20.500.12556/RUL-150188 This link opens in a new window
UDC:616-006(043.2)
COBISS.SI-ID:164536323 This link opens in a new window
Publication date in RUL:15.09.2023
Views:538
Downloads:23
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Secondary language

Language:English
Title:The role of melanoma antigens (MAGE) and cannabinoid receptors in disease development and response to therapy in hormone-dependent breast cancer cells
Abstract:
Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in women worldwide. The prognosis of the disease and the response to different types of treatment vary in different subgroups of this heterogeneous disease. The sub-groupings are based on the histological and molecular characteristics of the tumor, in particular the expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2. Hormone-dependent breast cancer (HDBC) is the most common type of breast cancer. Melanoma antigen (MAGE) expression is associated with poorer clinical prognosis and treatment resistance in many types of cancer, including breast cancer but their role in HDBC is unknown. The response to treatment can also be affected by the concomitant use of alternative treatments, such as cannabinoids, which are popular among patients. Cannabinoids interfere with the action of endogenous estrogens, but how they affect breast cancer treatment is still poorly understood. The aim of our work was to determine the expression of hormone receptors, cannabinoid receptors and MAGE proteins in HDBC cells by reverse transcription quantitative polymerase chain reaction, complement it with bioinformatics analysis and evaluate the response of HDBC cells to doxorubicin, cannabidiol, tamoxifen and estradiol treatment. Our studies determined the expression of several MAGE proteins and cannabinoid receptors in hormone-dependent breast cancer cell lines. We found that the cells HDBC respond better to chemotherapy than triple-negative breast cancer cells and as expected to respond better to hormone therapy. Interestingly, we found that the HDBC cell line MCF7 responded better to a combination of tamoxifen and cannabidiol hormone therapy, suggesting that HORD patients might benefit from alternative cannabidiol therapy as an adjunct to hormone therapy. However, further research is still needed.

Keywords:Hormone-dependent breast cancer, MAGE, cannabinoid receptors

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