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Viroterapi ile kombine hekzokinaz 2 inhibisyonu ile HPV negatif kolon kanserinin hedeflenmesi

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Abstract (EN)

Colorectal cancer is the third most common type of cancer among the Iraqi population. This type of cancer is difficult to treat and can be chemotherapy-resistant. Therefore, it is necessary to develop unconventional therapies to overcome these difficulties. First, we investigated the expression of the HK enzyme in the CRC patients as a possible target for therapy. The study was conducted on 30 individuals: the first group was 25 patients with CRC, and the second group was 5 healthy volunteers. HK was positively detected in all tissue samples of colorectal cancer, with significant intracellular expression (P < 0.0001) compared to non-malignant tissue samples. The results of the examination for HPV also showed a low expression of the infection (approximately 16%). Overexpressed HK could be used as a target for treatment in advanced stages of cancer. The main goal of fighting colorectal cancer cells is to use drugs that stop glycolysis along with oncolytic virotherapy as a safe and selective tumor-killing agent. HRT-18 was used as a model to study the HK inhibition and cytotoxicity of the NDV AMHA1 Iraqi strain as an oncolytic virus. When DM was used to target HK, it stopped HK2 from working in HRT-18 cells in the lab. NDV and an enzyme inhibitor can modulate differentiation and induce apoptosis in colon cancer cell lines. DM acts biologically by inhibiting glycolysis, thereby inhibiting tumor growth. HRT-18 cells exposed to NDV showed a significant killing effect compared to untreated control cells. When NDV and DM work together, they make cytotoxicity higher, slow cell growth by blocking glycolysis, and boost apoptosis in colon cancer cells in the lab, which is better than using either one alone. Significant reductions in HK and pyruvate concentrations have been identified across all treatment modalities in colon cancer cells. The synergy between NDV and DM can be considered a new strategy for future treatment of cancer cells. Finally, (AO/PI) double staining confirmed the ability of the combination treatment to induce apoptosis of HRT-18 cells at a higher magnitude than the application of single treatments. In conclusion, combination treatment enhanced antitumor activity against colorectal cancer cells and showed strong synergism that may indicate a promising cancer treatment.

Author

Dandan Abdulwahıd Badoo Badoo

How to Cite

Dandan Abdulwahıd Badoo Badoo (Doctorate thesis). Viroterapi ile kombine hekzokinaz 2 inhibisyonu ile HPV negatif kolon kanserinin hedeflenmesi, 2024, Çankırı Karatekin Üniversitesi.

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