Project description:Modulated electro-hyperthermia (mEHT) is a selective cancer treatment used in human oncology complementing other therapies. During mEHT, a focused electromagnetic field (EMF) is generated within the tumor, by elevated oxidative glycolysis (Warburg effect) and conductivity of the tumor. The EMF induce cell death by thermal and non-thermal effects. Here we investigated an aggressive, therapy resistant triple negative breast cancer (TNBC) model. 4T1/4T07 isografts inoculated orthotopically into female BALB/c mice were treated with mEHT 3-5 times. mEHT induced the upregulation of the stress related Hsp70 and cleaved caspase-3 proteins, resulting in effective inhibition of tumor growth and proliferation.
Project description:HT-29 human colorectal adenocarcinoma cells were xenografted into both femoral regions of 6 to 8-week old Balb/c (nu/nu) mice. After 18 days electromagnetic heat treatment was performed. We used microarray technology to identify the heat treatment releted gene expression alterations using human tumor xenograft mouse model.
Project description:HT-29 human colorectal adenocarcinoma cells were xenografted into both femoral regions of 6 to 8-week old Balb/c (nu/nu) mice. After 18 days electromagnetic heat treatment was performed. We used microarray technology to identify the heat treatment releted gene expression alterations using human tumor xenograft mouse model. Fresh frozen tissue sections were performed from the xenograft and tumorous regions were microdissected for total RNA isolation and gene expression analysis purposes.
Project description:Hyperthermia (HT) is widely used to treat patients with various cancers. In general, HT elicits a wide spectrum of stress responses such as induction of heat shock proteins, protein aggregation and cell death in mammalian cells. Although many biological processes are affected by HT, the overall responses to HT in mammalian cells remain unknown. The effects of heat stress at 41°C for 30 min (mild hyperthermia) on the gene expression in human cervical squamous cell carcinoma HeLa cells were investigated using an Affymetrix GeneChip system.
Project description:Hyperthermia (HT) is widely used to treat patients with various cancers. In general, HT elicits a wide spectrum of stress responses, such as induction of heat shock proteins, protein aggregation and cell death in mammalian cells. Although many biological processes are affected by HT, the overall responses to HT in mammalian cells remain unknown. The effects of heat stress at 41°C for 30 min (mild hyperthermia) on the gene expression in human oral squamous cell carcinoma HSC-3 cells were investigated using an Affymetrix GeneChip system.
Project description:The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in epithelial ovarian cancer (EOC) is still controversial partly because of the poorly understood mechanism of action. Further an understanding of the underlying mechanisms could identify potential combination therapies. Here, we conduct a comprehensive multi-omics study (transcriptiome, proteome, and phosphoproteome) upon hyperthermia (HT) in ovarian cancer cells. Unbiased trans-omics approach deciphered a unique hyperthermia- induced molecular panorama and demonstrated rapid alterations in protein phosphorylation as the primary cell response upon HT. Based on the phospho-signature, we identified CDK kinases to be hyperactivated and responsible for the global signaling landscape upon HT. Molecular and functional experiments demonstrated the dynamic and reversible CDK activity, subsequent replication arrest, and early mitotic entry after HT. A follow-up drug screen identified WEE1 inhibition to synergistically kills cancer cells with HT. An in-house developed miniaturized devise delivered proof-of-concept that the combination of hyperthermia with WEE1i leads to dramatic anti-tumor responses in vivo. These findings provide new insights into how to improve the effectiveness of HIPEC in EOC.
Project description:Purpose: Identify genes regulated by GPR126 in colon cancer cells by RNA-seq analysis Methods: Use shRNAs to knock down GPR126 in HT-29 cells, total RNAs from scramble group (NC) and GPR126 knockdown group (Sh1) were subjected to RNA-sequencing. Results: Around 700 transcriptomes were up-regulated in GPR126 knockdown HT-29 cells, and 14000 transcriptomes were down-regulated in GPR126 knockdown HT-29 cells.GPR126 mainly regualtes genes from DNA synthesis and cell cycle-related pathways. Conclusions: Our study firstly showed the function of GPR126 regulating colon cancer cell proliferation by targeting genes invovled in DNA synthesis and cell cycle-related pathways.
Project description:Low intracellular folate levels diminish the growth rate of HT-29 human colon cancer cells. This is accompanied by a metabolic shift from cytosolic glycolysis towards mitochondrial oxidative phosphorylation, as demonstrated by a lower lactate production and an increased mitochondrial oxygen consumption rate. To obtain insight in the molecular effects underlying these changes, the steady state gene expression profiles of HT-29 cells with different intracellular folate concentrations were compared. The gene expression profile of HT-29 cells with low intracellular folate levels (grown for 3 weeks in 10 ng/ml folic acid (PGA)) was clearly distinct from that of the other exposure conditions, which provide sufficient intracellular folate levels (100 ng/ml PGA, 10 ng/ml methyltetrahydrofolate (MTHF) or 100 ng/ml MTHF). Intracellular folate deficiency, contrary to expectation, did not lead to major changes in expression of genes involved in energy metabolism. This suggests that the shift towards mitochondrial oxidative phosphorylation is not mediated at the transcription level. Furthermore, only minor changes in the expression of folate metabolism related genes were observed. The changes that were observed were consistent with nucleotide salvage and in agreement with nucleotide need of the slow-growing folate-deficient HT-29 cells. The major observed effects were on cell cycle related gene expression, which was increased and interferon-responsive gene expression, which was reduced. The increase in cell cycle related gene expression seems compensatory to the reduced cell growth. Down-regulation of the interferon-response may be explained by decreased expression of signal transducer and activator of transcription 1 upon folate deficiency. Keywords: dose response, folic acid, HT-29 cells, human
Project description:By employing a global gene expression profiling, we performed the differential gene expression analysis and the analysis of the molecular pathways which are deregulated in Hyperthermia (HT) and Radiation therapy (RT) treated SAS and FaDu spheroids from the head-and-neck cancer cell lines. The RNA-Seq analysis was done on FaDu and SAS spheroids treated with clinically relevant HT dose of 42.5°C for 60 minutes alone or in combination of single dose irradiation of 7 and 10 Gy for FaDu and SAS, respectively. The main pathways and networks modulated by the treatments (0.5 h after treatment) were identified using Gene Ontology (GO) enrichment analysis.