Project description:Abstract Background: Several studies on the use of erythropoietin (Epo) to treat anaemia in patients undergoing cancer treatment have shown adverse effects on tumour control and survival. Experimental studies indicate that this could be linked to an interaction with wound healing processes and not an effect on tumour cells per se. We have previously shown that erythropoietin in combination with surgical trauma stimulates tumour growth. In the present study, we investigated the effect of surgery and Epo on gene expression. Methods: Human tumours from oral squamous cell cancer were xenotransplanted to nude mice treated with Epo. The tumours were then transected in a standardised procedure to mimic surgical trauma and the change in gene expression of the tumours was investigated by microarray analysis. qRT-PCR was used to measure the levels of mRNAs of pro-apoptotic genes. The frequency of apoptosis in the tumours was assessed using immunohistochemistry for caspase-3. Results: There was little change in the expression of genes involved in tumour growth and angiogenesis but a significant down-regulation of the expression of genes involved in apoptosis. This effect on apoptosis was confirmed by a general decrease in the expression of mRNA for selected pro-apoptotic genes. Epo-treated tumours had a significantly lower frequency of apoptosis as measured by immunohistochemistry for caspase 3. Conclusions: Our results suggest that the increased tumour growth during erythropoietin treatment might be due to inhibition of apoptosis, an effect that becomes significant during tissue damage such as surgery. This further suggests that the decreased tumour survival during erythropoietin treatment might be due to inhibition of apoptosis. Key words: Erythropoietin, Head and neck cancer, surgery, apoptosis, wound healing, xenograft. We wanted to study the effect of wound healing mechanisms on remaining tumour tissue efter incomplete surgery or biopsy. We xenografted human Head and Neck squamous Cell Cancer (HNSCC) tumours on Balb/c nude mice. The mice were divided in six groups. Three of the groups received intrapertoneal doses of erythropoietin (Epo) and the other three groups were given NaCl as placebo. One treated and one non-treated group were harvested without surgical transection. In the other four groups, the tumours were transected mimicking subtotal surgery. One Epo-treated and one non-treated group was analysed after 24 hours after transection and the remaining two groups 48 hours after surgery. Groups C and D were not analyzed due to harvesting at an unsuitable time interval. Group A No surgery (=FALSE) + Epo Group B No surgery (=FALSE) + NaCl Group E Surgery (=TRUE) + Epo 24 hours after surgical transection Group F Surgery (=TRUE) + NaCl 24 hours after surgical resection Group G Surgery (=TRUE) + Epo 48 hours after surgical transection Group H Surgery (=TRUE) + Nacl 48 hours after surgical transection

Project description:Background: Gene expression profiling has been used extensively within breast cancer research. Patient matched transcriptomic studies of tumour samples before and after treatment offer great potential and have been initiated, but tend not to include a control group. Here we examine gene expression changes between patient-matched core biopsies and surgical resection samples in the absence of treatment, to consider sampling methods and tumour heterogeneity. Patients and Methods: Illumina BeadArray technology was used to measure dynamic changes in gene expression from thirty-seven paired baseline and surgically excised breast tumour samples obtained from women receiving no treatment prior to surgery. Results: Patient-matched sample pairs had significantly higher correlations than samples between different individuals, demonstrating that tumour heterogeneity and intra-tumour differences are less prominent than inter-tumour/patient differences. Perhaps surprisingly, consistent changes in gene expression were identified during the diagnosis-surgery interval, despite a lack of treatment. 50 genes were significantly differentially expressed (48 up, 2 down; FDR 0.05) in a manner that appears independent of both subtype and the sampling-interval length. Gene set enrichment analysis using four independent treated datasets has implicated the tumour sampling method as the likely cause of these expression changes which include increases in early growth response genes such as EGR1, 2 and 3 along with DUSP1 and FOS. Our data does not support the idea that there is a significant wounding or immune response. Conclusion: This is the largest cohort of patient-matched transcriptome profiling of tumours from patients receiving no treatment between diagnosis and surgery to date. It has revealed that consistent changes in gene expression do exist between diagnostic core biopsy and the surgical excision sample. We have confirmed these findings in a number of published breast cancer datasets. Ultimately, researchers should be aware of the potential for the tumour sampling method to introduce a confounding factor in future neoadjuvant studies. 37 paired patient-matched whole-transcriptome profiled primary breast tumours from patients receiving no treatment between diagnosis and surgery. Superseries is a product of two integrated individual batches.

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Erythropoietin suppresses the activation of pro-apoptotic genes in head and neck squamous cell carcinoma xenografts exposed to surgical trauma

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