Overcoming chemoresistance in non-angiogenic colorectal cancer by metformin via inhibiting endothelial apoptosis and vascular immaturity

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed independently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endothelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

Affinity peptide developed by phage display selection for targeting gastric cancer

AIM:To develop an affinity peptide that binds to gastric cancer used for the detection of early gastric cancer.METHODS:A peptide screen was performed by biopanning the PhD-12 phage display library,clearing non-specific binders against tumor-adjacent normal appearing gastric mucosa and obtaining selective binding against freshly harvested gastric cancer tissues.Tumortargeted binding of selected peptides was confirmed by bound phage counts,enzyme-linked immunosorbent assay,competitive inhibition,fluorescence microscopy and semi-quantitative analysis on immunohistochemistry using different types of cancer tissues.RESULTS:Approximately 92.8% of the non-specific phage clones were subtracted from the original phage library after two rounds of biopanning against normal-appearing gastric mucosa.After the third round of positive screening,the peptide sequence AADNAKTKSFPV(AAD) appeared in 25%(12/48) of the analyzed phages.For the control peptide,these values were 6.8 ± 2.3,5.1 ± 1.7,3.5 ± 2.1,4.6 ± 1.9 and 1.1 ± 0.5,respectively.The values for AAD peptide were statistically signif icant(P < 0.01) for gastric cancer as compared with other histological classif ications and control peptide.CONCLUSION:A novel peptide is discovered to have a specific binding activity to gastric cancer,and can be used to distinguish neoplastic from normal gastric mucosa,demonstrating the potential for early cancer detection on endoscopy.

Percutaneous suture technique with ProGlide to manage vascular access pseudoaneurysm after percutaneous coronary intervention procedure: A case report

Iatrogenic femoral artery pseudoaneurysm is a common complication of the endovascular procedures.Manual compression and thrombin injection are the conventional techniques to occlude the pseudoaneurysms.However,there are still some failed cases that applied these treatment options.The aim of the study is to seek a potential and alternative method with ProGlide system to close the pseudoaneurysm.During April 2018 to February 2019,2 patients with iatrogenic pseudoaneurysm of the superficial femoral were treated with the suture-base closure device–ProGlide.After punctured the pseudoaneurysm and placed a 6-F sheath,the guide wire was placed in the right femoral artery via the access of the pseudoaneurysm neck.Then the pseudoaneurysm neck was sutured by ProGlide to occlude the blood supply to the pseudoaneurysm.These 2 patients were cured with no complications and complaints,which revealed that percutaneous suture technique with ProGlide at the neck level of pseudoaneurysm provides a novel method for the management of vascular access pseudoaneurysm,especially in those with a wide and short neck.

Iatrogenic femoral artery pseudoaneurysm surgically repaired with combined bovine pericardial roll and autologous great saphenous vein grafts

Iatrogenic femoral artery pseudoaneurysm caused by invasive procedures is one of the common complications for endovascular interventions.We present a case of a young male with a complex iatrogenic femoral artery pseudoaneurysm as a result of iatrogenic femoral artery puncture.The defective femoral artery was repaired with combined bovine pericardial tube and autologous great saphenous vein grafts.Computed tomography angiography showed the grafts were still patent one year after the surgery.