KFTX paclitaxel (PTX)-resistant ovarian cancer cells, KFTXlow PTX-resistant ovarian cancer cells and KFlow PTX-sensitive ovarian cancer cells expression profilies
Ontology highlight
ABSTRACT: Oncolytic vaccinia virus (OVV) has demonstrated appropriate safety profiles for clinical development. Although OVV was designed to kill cancer cells efficiently, sensitivity to OVV varies in individual cancers. Here, we found that OVV was much more efficient in KFTX paclitaxel (PTX)-resistant ovarian cancer cells, compared to that in KFlow PTX-sensitive cells. Microarray analysis showed that urothelial carcinoma-associated 1 (UCA1) upregulation contributed to both enhanced PTX resistance and OVV spread.
Project description:KFTX paclitaxel (PTX)-resistant ovarian cancer cells, KFTXlow PTX-resistant ovarian cancer cells and KFlow PTX-sensitive ovarian cancer cells expression profilies
Project description:Transcriptional profiling (lncRNA and mRNA) of human ovarian cancer cells comparing parental PTX-sensitive cells (OVCAR-3) vs. PTX-resistant cells (OV3R-PTX, derived from OVCAR-3).
Project description:LncRNA urothelial carcinoma-associated 1 (UCA1) is an oncogene in breast cancer. Previous reports indicates that lncRNAs may function as competing endogenous RNAs (ceRNAs) to sponge miRNAs, thereby modulating the derepression of miRNA targets. To characterize microRNAs that associated with UCA1, the microRNAs associated with UCA1 were extracted from the UCA1-MS2 RNP complexes and analyzed by miRNA-seq.
Project description:We investigated the mechanisms by which inflammatory responses generated by tumor-specific T cells delivered to ovarian tumor-bearing mice alone or after oncolytic vaccinia virus-driven immunogenic cancer cell death affect antitumor efficacy using spatial transcriptomics.
Project description:We investigated the mechanisms by which inflammatory responses generated by tumor-specific T cells delivered to ovarian tumor-bearing mice alone or after oncolytic vaccinia virus-driven immunogenic cancer cell death affect antitumor efficacy using scRNA-seq.
Project description:Human melanoma tumor cells (HS294T) and monocytes (THP-1) were infected with a double deleted (-VGF, -TK) oncolytic vaccinia virus expressing human DAI (DNA-dependent activator of interferon-regulatory factors). Total RNA was collected and gene expresson profiles were determined with Agilent microarray. An oncolytic vaccinia virus that does not express DAI was used to control the effect of DAI and uninfected cells (PBS treated) were used to control the effect of virus infection. In oncolytic virotherapy the ability of the virus to activate the immune system against tumors is nowadays generally understood to be a key mechanism in full eradication of cancer and for long-term anti-tumor effects. We armed an oncolytic vaccinia virus with DAI to increase the immunogenicity and the vaccine potency of the virus. The aim of this study was to study if the expression of DAI by a replicating vaccinia virus would alter the gene expression profile of infected cells and to study what are the differentially expressed genes.
Project description:Resistance to anti-cancer drugs is the main challenge in oncology. In pre-clinical studies established cancer cell lines are primary tools in deciphering molecular mechanisms of this phenomenon. In this study we proposed a new approach, based on a model of isogenic cancer cell lines with gradually changing resistance. We analyzed trends in gene expression to find out a scaffold of resistance development process. Ovarian cancer cell line A2780 was treated with stepwise increased concentrations of paclitaxel (PTX) to generate a series of drug resistant sublines. To monitor transcriptome changes we submitted them to mRNA-sequencing, followed by identification of differentially expressed genes (DEGs), principal component analysis (PCA) and hierarchical clustering. Functional interactions of proteins, encoded by DEGs, were analyzed by building protein-protein interaction (PPI) networks. We provided a model of human ovarian cancer cell lines with gradually developed resistance to PTX and collateral sensitivity to cisplatin (CDDP) (inverse resistance). In their transcriptomes we identified two groups of DEGs: 1) with fluctuations in expression in the course of resistance acquiring; and 2) with consistently changed expression in each stage of resistance development, constituting a scaffold of the process. In the scaffold PPI network, cell cycle regulator – PLK2; proteins belong to TNF ligand and receptor family as well as ephrin receptor family were found, but proteins linked to osteo- and chondrogenesis and nervous system development turned out to be key players. Our cellular model of drug resistance allowed for keeping track of trends in gene expression and studying this phenomenon as a process of evolution. This approach revealed that abrogation of osteomimic phenotype in ovarian cancer cells may occur during the development of inverse resistance to PTX and CDDP.
Project description:ATC is a very rare, but extremely aggressive form of thyroid malignancy, responsible for the highest mortality rate registered for thyroid cancer. In the patients without known genetic aberrations, the current treatment is still represented by palliative surgery and systemic mono- or combined-chemotherapy, which is often not fully effective for appearance of drug resistance. Comprehension of the mechanisms involved in the development of the resistance is therefore an urgent issue to suggest novel therapeutic approaches of this very aggressive malignancy. In this study, we created a model of anaplastic thyroid cancer (ATC) cells resistant to paclitaxel, to investigate the characteristics of these cells by analyzing the profile of gene expression and comparing with that of paclitaxel-sensitive original ATC cell lines. In addition, we evaluated the effects of Dihydrotanshinone I (DHT) on the viability and invasiveness of paclitaxel-resistant cells. ATC paclitaxel-resistant cells highlighted an overexpression of ABCB1 and a hyper-activation of the NF-κB compared to sensitive cells. DHT treatment results in a reduction of cell viability, and clonogenic ability of resistant cells. Moreover, DHT induces a decrement of NF-κB activity in SW1736-PTX and 8505C-PTX cells. In conclusion, to the best of our knowledge, the results of the present study are the first to demonstrate the antitumor effects of DHT on ATC cells resistant to Paclitaxel in vitro.
Project description:RNA-sequencing was performed in SUM 159 parental and PTX resistant breast cancer cells in an effort to identify novel regulators of chemoresistance that could potentially be targeted in Triple Negative Breast Cancer (TNBC). The bioinformatic analysis identified numerous differentially expressed genes including several known chemoresistance markers, as well as novel genes that may play an important role in breast cancer chemoresistant cells.