Oral Presentations

Background and Aim: Neoplastic cells need essential metals such as iron and copper for cellular functions and rapid growth. In breast cancer cells, human epidermal growth factor receptor 2 (HER2) is overexpressed around 30% with poor prognosis and this results in elevated the proportion of cancer stem cells (CSCs) that are in charge of cancer recurrence. Metal chelation and changing their redox cycle in favor of oxidative stress may be a critical to make these cells vulnerable to cell death. Investigating whether metal chelation alters HER2-induced CSC population may provide a new tools for breast cancer therapy. Material and Methods: MCF7-HER2, overexpressing HER2, and MCF7-vec control cells were used to evaluate the effect of HER2. Also, we have used other breast cancer cell lines; HCC1954, MDA-MB-435 and Hs578T in order to substantiate our results. DFO and Dp44mT were used as metal chelators. ROS production, iron levels and CSC survival in response to chelators were detected by flow cytometry and cell viability was measured by MTT assay. Results: MCF7-HER2 cells require iron more than their vector counterparts and HER2-increased CSCs are vulnerable to iron chelation. Additionally, this sensitivity of CSCs to iron reduction is obviously indicated in other breast cancer cell lines. Finally, the concept also in neoplastically transformed breast cancer cell line, HMLER. ROS were relatively increased by Dp44mT in the cells this was reversed by combination of iron while copper combination further induced ROS. Parallel changes were observed in the inhibition of cell growth by Dp44mT and this was partially rescued by NAC supplement. Discussion Conclusion: study cancer cells fluorescence which covers pathogenic or beneficial Mc. We focused on do Mc play any role in carcinogenesis. Neuroblastoma (NB) is the most common extracranial solid cancer in childhood. Cancer stem cells (CSCs) are thought to be associated with micrometastasis, cause of cancer,drug resistance and recurrences. Recent studies showed that sanguinarine (Sng) could used as an anti-cancer due to its apoptosis inducing mechanism. FBS is used as a common supplement in most of the in vitro studies however there are other factors interacting with tumor cells and CSCs in in vivo conditions. Thus, the aim of this study was to evaluate the effect of Sng on NB CSCs in different culture conditious. patients with breast cancer is not satisfactory. In recent years, this failure attributed to cancer stem cells (CSCs) as they show and/or gain resistance to therapies. Thus, compounds that target CSCs are urgently needed. The aim of this study is to investigate the cytotoxic activity of tingenin b (or 22β-hydroxytingenone, a quinone-methide triterpenoid structurally related to tingenone) in combination with paclitaxel against breast CSCs. Material&Methods: The anti-growth activity was investigated by the ATP assay. Mode of cell death was evaluated using fluorescence microscopy (Hoechst 33342+Propidium iodide staining), western blotting (apoptosis related markers) and flow cytometry (annexin v staining, determination of caspase 3/7 activity, mitochondrial membrane potential, BCL-2 and PI3K expressions). Results: It has been found that combination of tingenin b and paclitaxel enhanced the cytotoxic activity and apoptotic cell death at 72 h, compared to single use of each agent in MCF-7s (cancer stem cell enriched population). Apoptosis was evident by the presence of pyknotic nuclei, annexin v staining positivity, increased caspase 3/7 activity, Bcl-2 inactivation, cleavage of PARP and increased expression of Bax. The PI3K/AKT pathway was also found to be inhibited by this combinatorial treatment. In addition, the stemness factor, Oct4, was also found to be decreased. Discussion: The combination of tingenin b and paclitaxel exerted a promising cytotoxic and apoptotic effect on cancer stem cells of breast cancer. Therefore, the application of this combination may be regarded as a novel and effective approach for due to its cytotoxic activity and apoptosis inducing effect against breast CSC although in vivo experiments are required for the proof-of concept. in both cells, we suggest that these cells may be dying via autophagy. However, analysis of the expressions of autophagy related proteins (p62 and LC3-II) revealed a process in which autophagic flux was blocked rather than being stimulated. Furthermore, apoptotic cell death was found to harbor endoplasmic reticulum stress and unfolded protein response (UPR) in breast cancer cells. Lastly, pristimerin inhibited the growth of MCF-7 and MDA-MB-231 xenografts. In these tumors, Pristimerin reduced the expression of Akt and PCNA. Besides, the cleavage of PARP, and levels of PTEN, active caspase 3 and/ or 7, LC3B, TUNEL stainings were found to be increased. Discussion: Collectively, pristimerin exerted both in vitro and in vivo cytotoxic and anti-growth effects on breast cancer cells. Our observations identified a mechanism by which pristimerin functions as an anticancer agent. S42,T121, and S123 acids are important for the activation of Twist1. Thus, Twist1 and PI3K-AKT/PKB pathway plays an important role in induction of metastasis. In this context, Twist1 could be evaluated as a new therapeutic molecule in cancer therapy. role in the metastasis and progression of BCa and targeting Na V 1.5s by siRNA may be beneficial to BCa patients. Mechanisms that regulate TGF-beta receptor I/II (TßRI/II) trafficking to primary cilia membrane for mediating signal transduction remain unknown. Here, we show that ceramide synthase 4 (CerS4) generated ceramide, bioactive sphingolipid, stabilized Smad7-TßRI association, which then inhibited the trafficking of TßRI/ II to primary cilia membrane. Expression of a mutant TßRI, which is resistant to Smad7 binding/inhibition, restored receptor signaling to increase migration in response to CerS4/ceramide induction. Genetic or molecular alterations of CerS4 abundance prevented Smad7-TßRI inhibitory complex, and increased association between Arl6 transporter and TßRI via novel cilia targeting signal (31-ATALQ-35). Mutation of the cilia targeting signal abolished the trafficking of the receptor to the cilia membrane in response to CerS4 knockdown in various cell types. Localization of TßRI/II to primary cilia activated sonic hedgehog (Shh) receptor smoothened (Smo), inducing migration/invasion and liver metastasis both in wild type and CerS4-/- knockout mice in response to endogenous CerS4/ceramide knockdown in 4T1 mammary cancer cells, injected in the mammary pads. Smad7 overexpression or primary cilia inhibition by shRNA-mediated knockdown of intraflagella transport protein 88 (IFT88) prevented TßRI-Smo crosstalk and attenuated liver metastasis of mammary cancer cells stably transfected with shRNA against CerS4/ceramide. Overall, these data define a key mechanism for the regulation of TßRI/II targeting selectively at the primary cilia membrane by CerS4/ceramide-Smad7 inhibitory complex to control Shh-mediated cell migration and invasion without affecting canonical TGF-ß signaling. Aim: Although epithelial to mesenchymal transition (EMT) is a biological event applicable to all tumor types studied so far, published gene signatures defining the epithelial or mesenchymal status of cancer cells or tissues have been mostly tissue specific. Recent studies showed that EMT status can be determined with certain gene lists independent of tissue-type. In this study, we aimed to identify drugs with differential effects on mesenchymal, and epithelial groups regardless of the tissue type. Methods: We used one gene list determining EMT status of cancer cell lines (1), as well as one we generated ourselves to analyze in silico several cell line panels (2,3), and defined the compounds which can selectively inhibit the growth of epithelial and mesenchymal cells. Results: We thus identified compounds that caused growth inhibition of either epithelial or mesenchymal cells, and observed groups of drugs behaving in a similar pattern. Proteomic analysis of cell lines within each group identified pathways related to sensitivity of drug subgroups. Our analysis revealed that the EMT based classification was also related to the stemness status of cancer cell lines. Conclusion: Our study demonstrates a novel use for online databases and might help us understand the major mechanisms that should be targeted for both types of cancer cells. (MM) a show expression B transcription utilized bortezomib-sensitive KMS-28 and bortezomib-resistant KMS-20 human MM cell lines. These cells were treated with different concentration of bortezomib for 12, 24 and 48h. The effects on cell viability of bortezomib were determined using the MTT assay. The expression levels of NF-kB p65 and p50 subunits were determined by real time RT-PCR method. Results: Bortezomib time and dose dependently reduced cell viability in MM cells. In bortezomib-sensitive KMS-28 cell line, IC50 values were 11.83, 5.30, 3.67 nM at 12, 24 and 48h, respectively. In bortezomib-resistance KMS-20 cell line, IC50 values were 32.06, 15.62, 6.05 nM at 12, 24 and 48h, respectively. In KMS-28 cell line, the expression levels of p65 and p50 did not show any change with dose and time dependent. Moreover, the expression levels of NF-kB/p65 were observed increased in a dose dependent manner in bortezomib resistant KMS-20 cells, whereas no changes were observed in the NF-kB/p50 levels. Conclusion: Bortezomib-resistance in MM cells can be associated with increasing of NF-kB/p65 expression levels in the high bortezomib concentrations activity in normal PNT-1 cells. Conclusion: CA inhibition can decrease cell proliferation and induce apoptosis in human tumour cells. The ability of CA inhibitors to increase ROS might trigger cell apoptosis. Activation of this apoptotic cascade is probably mediated by inhibition of the CA IX isoform. is the primary medicine of GBM. But sometimes GBM can gain