Pancreatic cancer is one of the most aggressive cancer due to the late diagnosis and failure to respond to the treatment despite advances in tumor biology and the development of new cancer therapeutic strategies. It has been reported that these characteristics of pancreatic cancer originate from cancer stem cells within the tumor mass. It has also been reported that Fentanyl is a fast-acting analgesic that binds to the mu-opioid receptors and some other mu-opioid receptors are involved in this cancer process. In this study, we determined the effect of Fentanyl on PANC-1 cells, by assessing the gene expression of cancer stem cell marker genes (Nanog, Oct4, and Sox2) and apoptosis-related genes (BAD, Bax, Bcl-2, and p53) by Quantitative RealTime PCR. The number of cancer stem cells was determined by Flow Cytometry. The results of our study showed that Fentanyl administration decreased the number of cancer and cancer stem cells in the PANC-1 cell population, decreased the gene expression of stem cell marker and increased the expression of apoptosis-related genes. These results indicate that Fentanyl, which is used routinely in the pain palliation of pancreatic cancer, can be considered as an option in the treatment of pancreatic cancer.

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumors of the pancreas. Preclinical studies show that it evades the immune system with immune checkpoints and promotes tumor development. V-domain Ig suppressor of T cell activation (VISTA) is a new immunecheck point from the B7 family and is highly expressed in cancer cells. Overexpression of toll like receptor 4 (TLR4) in pancreatic adenocarcinoma is associated with inducing tumorigenesis, tumor growth and resistance to chemotherapy. Naloxone is an opioid and inhibits TLR4-ligand association. In this study, we investigated the connection of TLR4 and downstream pathway with immune-check point VISTA in pancreatic cancer proliferation. We rst collected pancreatic cancer-related datasets using the GEPIA2 and UALCAN databases. Based on the data obtained the effect of different concentrations and incubation times of Naloxone were used on PANC-1 cells proliferation. Combination of Naloxone and VISTA-siRNA were applied, and effect of both Naloxone and combined reatment on TLR4, Interleukin 1 receptor associated kinase 4 (IRAK4) and VISTA gene expression were analysed in pancreatic cancer cells. As a result of analysis with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), gene expression levels of TLR4, IRAK4 and VISTA were signi cantly suppressed and cell proliferation was signi cantly reduced. We found that administration of Naloxone and VISTA-siRNA in combination to PDAC cells suppressed signaling. Therefore, we considered that the relationship between VISTA and TLR4 signaling pathways and the other possible associated signal molecules may be an important marker in determining the response of immune checkpoint inhibitors in cancer treatment.

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Objective: Nigella sativa, commonly known as the black seed, has been used since ancient times in folk medicine, and its various therapeutic benefits have been mentioned in some ancient medical sources and confirmed by modern science. Thymoquinone is the major compound and essential active ingredient of Nigella sativa seed oil. Thymoquinone has been reported to have high biological activity and broad therapeutic potential through several mechanisms that affect cells including anti-oxidant, anti-inflammatory, and anti-tumor properties. Although it has been widely reported that Thymoquinone inhibits cell growth and proliferation and stimulates apoptosis in various types of cancer cells, the mechanisms and signaling pathways are not fully understood. The aim of this study was to determine the effect of Thymoquinone on apoptosis in both tumor and non-tumor cells. Methods: In this study, breast cancer cell line (MCF-7) was used as tumor cells and Human Embryonic Kidney Cell line (HEK293) was used as non-tumor cells. Cells were treated with Thymoquinone and viability test performed by MTT assay.Gene expression of apoptosis markers such as Bax, BAD, Bcl-2, and p53 was determined by Real-Time PCR. HEK293 cells were used as non-tumor control. Results and Conclusion: Results suggest that Thymoquinone has a strong effect on cell proliferation and vitality. Thymoquinone has increased the expression of BAD, Bax genes which induce apoptosis and decreased the p53 gene in breast cancer cells. Therefore Thymoquinone promotes apoptosis and enhances anti-cancer efficacy in breast cancer cells.

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Yeasts are usually found in high amounts in dairy products, which show their ability to adapt to substrates rich in protein, lipid, sugar and organic acids. A wide distribution of yeast in dairy products is a result of proteolytic and lipolytic activities. Spoilage yeasts and molds can grow in most processed and raw foods, where environmental conditions are not suitable for most bacteria (low pH, low water activity, aw). Nutrients and oxygen in food are the main factors that determine the type of fungal spoilage. In this study, dairy products samples (yoghurt, cream, butter, curd cheese, Antep cheese) were collected from local markets in Gaziantep province. In our study, a total of 20 yeast strains were isolated from dairy products and investigated for lipase activities in solid media containing tributyrin. Twenty yeast isolates identified by amplification and sequencing of the ITS region using ITS1 and ITS4 primers Yeasts were identified as Kluyveromyces marxianus (8 isolates), Candida intermedia (8 isolates), Pichia fermentans (2 isolates), Yarrowia lipolytica (1 isolate), Kluyveromyces lactis (1 isolate).