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.

Liver fibrosis promotes immune escape in hepatocellular carcinoma via GOLM1-mediated PD-L1 upregulation.

Immune checkpoint blockade is considered a breakthrough in cancer treatment. However, with the low response rates and therapeutic resistance of patients with hepatocellular carcinoma (HCC), the challenges facing the application of this treatment are tremendous. Liver fibrosis is a key driver of tumor immune escape, the underlying mechanism has never been clarified.

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.

SRY is a Key Mediator of Sexual Dimorphism in Hepatic Ischemia/Reperfusion Injury.

Objectives: To identify the role and mechanism of a male specific gene, SRY, in I/R-induced hepatic injury.

Background: Males are more vulnerable to I/R injury than females. However, the mechanism of these sex-based differences remains poorly defined.

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.

Metformin inhibits metastatic breast cancer progression and improves chemosensitivity by inducing vessel normalization via PDGF-B downregulation.

Background: Vascular maturity and functionality are closely associated with tumor progression and chemosensitivity. The antidiabetic agent metformin has shown its ability to inhibit tumor angiogenesis in metastatic breast cancer models. However, it remains unclear if or how metformin remodels the abnormal vasculature of metastatic breast cancer, while inhibiting angiogenesis.

Metformin's antitumour and anti-angiogenic activities are mediated by skewing macrophage polarization.

Beneficial effects of metformin on cancer risk and mortality have been proved by epidemiological and clinical studies, thus attracting research interest in elucidating the underlying mechanisms. Recently, tumour-associated macrophages (TAMs) appeared to be implicated in metformin-induced antitumour activities. However, how metformin inhibits TAMs-induced tumour progression remains ill-defined.

A Comparison of Concomitant Tributary Laser Ablation and Foam Sclerotherapy in Patients Undergoing Truncal Endovenous Laser Ablation for Lower Limb Varicose Veins.

Purpose: To compare outcomes of patients who received simultaneous tributary endovenous laser ablation (EVLA) or foam sclerotherapy (FS) with EVLA of the great saphenous vein (GSV) trunk.

Methods And Materials: This study recruited 418 patients (542 legs) with diagnosed varicose veins. Patients in the EVLA/FS group (255 patients, 327 legs) received concomitant FS for the tributaries with truncal lasering.

Activation of AMPK by simvastatin inhibited breast tumor angiogenesis via impeding HIF-1α-induced pro-angiogenic factor.

Substantial data from preclinical studies have revealed the biphasic effects of statins on cardiovascular angiogenesis. Although some have reported the anti-angiogenic potential of statins in malignant tumors, the underlying mechanism remains poorly understood. The aim of this study is to elucidate the mechanism by which simvastatin, a member of the statin family, inhibits tumor angiogenesis.

A CD44 specific peptide developed by phage display for targeting gastric cancer.

Objective: To develop a peptide probe that could be used for gastric cancer detection via binding to CD44 protein with specificity and affinity.

Results: A 12-mer phage peptide library was screened against immobilized CD44 protein. Bound phage counts using ELISA were performed to identify phage clones carrying the most highly selective peptide, which termed RP-1.

Recombinant lentivirus with enhanced expression of caudal-related homeobox protein 2 inhibits human colorectal cancer cell proliferation in vitro.

Caudal-related homeobox protein 2 (CDX2), a tumor suppressor in the adult colon, is overexpressed under a non-cancer specific cytomegalovirus promoter in certain tumor cells; furthermore, non-specific expression of CDX2 may result in aberrant side effects in normal cells. The human telomerase reverse transcriptase (hTERT) promoter is active in the majority of cancer cells but not in normal cells. Hypoxia is a key feature of solid tumors, and targeted genes may be significantly upregulated by five copies of hypoxia-response elements (HREs) under hypoxic conditions.

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. Tumor-targeted 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.

Effects of homeodomain protein CDX2 expression on the proliferation and migration of lovo colon cancer cells.

The homeobox gene, CDX2, plays a major role in development, especially in the gut, and also functions as a tumor suppressor in the adult colon. In the present study, we investigated the effects of CDX2 expression on the proliferation, migration, and apoptosis of the human colon cancer cell line, Lovo. Lovo cells exogenously expressing CDX2 exhibited no significant differences in the percentage of cells in G1- and S-phase or in apoptosis, as determined by flow cytometry.

[Construction of recombinant plasmid pIRES2-EGFP/CCK and its expression in vivo and in vitro].

Objective: To construct eukaryotic expression plasmid of porcine CCK gene pIRES2-EGFP/ CCK and express it in COS-7 cells and hamsters.

Methods: The aimed segments were obtained from intermediate vector pMD18-T/CCK by the method of restricted enzymatic resection and were inserted into a eukaryotic expression plasmid pIRES2-EGFP to construct a recombinant expression plasmid pIRES2-EGFP/CCK. The recombinant expression plasmid was transfected into COS-7 cells by liposome-mediated gene transfer method and observed through Fluorescence microscopy.

Identification of HLA-A2-restricted CTL epitope encoded by the MAGE-n gene of human hepatocellular carcinoma.

Background: Identification of the cytotoxic T lymphocytes (CTL) restricted epitopes of tumor antigens opens up possibilities of developing a new cancer vaccine. For the MAGE-n has been demonstrated closely associated with hepatocellular carcinoma (HCC) and HLA-A2.1 is found in over 50% of HCC patients in China, we aim at identifying MAGE-n-encoded peptide presented by HLA-A2.

Efficient induction of cytotoxic T lymphocytes specific to hepatocellular carcinoma using HLA-A2-restricted MAGE-n peptide in vitro.

MAGE-n is a new member of MAGE gene family and has been demonstrated closely associated with hepatocellular carcinoma (HCC). In this study, MAGE-n-derived peptide-specific cytotoxic T lymphocytes (CTL) were induced from the peripheral blood mononuclear cells of healthy donors by multiple stimulations with HLA-A2-restricted MAGE-n peptide-pulsed T2 cells. The induced CTLs exhibited specific lysis against T2 cells pulsed with the peptide and HLA-A2+ HCC cells expressing MAGE-n, while HLA-A2+ HCC cell lines that did not express MAGE-n could not be recognized by the CTLs.

[Study on immunoreaction induced by DCs loaded with hepatocarcinoma antigen peptide in-vitro].

Aim: To investigate the potency and antitumor effect of specific cytotoxic T lymphocytes induced by hepatocarcinoma antigen peptide EPVTKAEML-loaded dendritic cells (DCs).

Methods: The healthy donors of HLA-B7 genotype were selected by PCR-SSP. Isolated and cultured DCs from HLA-B7 donors' spleen tissues were loaded with the peptide EPVTKAEML from hepatocarcinoma cell line HHCC.

[The construction and expression of a hepatocellular carcinoma-specific superantigen SEA (D227A) expression vector].

Aim: To construct the superantigen SEA (D227A) expression vector modulated by cis-acting element of AFP and express it specifically on AFP(+) hepatocellular carcinoma (HCC) cells.

Methods: The enhancer and promoter of AFP gene, SEA (D227A) cDNA and linker-CD80tm were amplified by PCR. The gene segments mentioned above were cloned into the multiple cloning sites of retrovirus vector pLXSN to construct an attenuated superantigen expression vector pLXSN-SEA (D227A)-linker-CD80tm modulated by cis-acting element of AFP gene.

[Construction of VEGF eukaryotic expression vector and its expression in endothelial cells and cardiac myocytes in-vitro].

Aim: To study the feasibility of VEGF165 gene transfection to endothelial cells and cardiac myocytes in-vitro.

Methods: The VEGF165 DNA fragment was inserted into a green fluorescent protein fusion vector, which was then transfected into endothelial cells and cardiac myocytes with lipofectamine.

Results: The endothelial cells and cardiac myocytes were successfully transfected with pIRES2-EGFP-hVEGF165 gene, which was confirmed by fluoroscopy and immunohistochemistry.

In vivo tumor co-transfection with superantigen and CD80 induces systemic immunity without tolerance and prolongs survival in mice with hepatocellular carcinoma.

Background: Since transfection of established tumors with immunostimulatory genes can elicit antitumor immunity, we treat mouse HCC with in vivo transfection of superantigen SEA and/or costimulatory molecule CD80 and evaluated the safety and efficacy.

Methods: Mice with HCC were treated with lipid-complexed plasmid DNA encoding staphylococcal enterotoxin A and/or CD80. Then the mice were evaluated for tumor regression, systemic immunologic responses, survival times and treatment-associated toxicity.

Superantigen-SEA gene modified tumor vaccine for hepatocellular carcinoma: an in vitro study.

Aim: To construct an eukaryotic superantigen gene expression vector containing the recombinant gene of SEA and CD80 molecule transmembrane region (CD80TM), and to express staphylococcus enterotoxin A (SEA) on the membrane of hepatocellular carcinoma (HCC) cell to form a superantigen gene modified tumor vaccine for HCC.

Methods: SEA and linker-CD80TM gene were amplified through PCR from plasmid containing cDNA of SEA and CD80. Gene fragments were then subcloned into the multiple cloning sites of retroviral vector pLXSN.

[Prediction synthesis and identification of HLA-A2-restricted cytotoxic T lymphocyte epitopes of the tumor antigen MAGE-n].

Objective: To predict, synthesize, and identify HLA-A2-restricted cytotoxic T lymphocyte (CTL) epitopes of the tumor the novel antigen MAGE-n.

Methods: Long-distance prediction system SYFPEITHI combined with polynomial method was used to predict the HLA-A2-restricted CTL epitopes of the tumor antigen MAGE-n. The candidate epitopes were synthesized with solid phase strategies, purified with reverse phase high-performance liquid chromatography and identified by mass spectrometry, The binding affinity and biding stability of the synthesized peptides were examined by cellular competition-based HLA-A2 peptide binding assay, T2 peptide stabilization assay, and peptide-major histocompatibility complex dissociation assay.

Construction of a regulable gene therapy vector targeting for hepatocellular carcinoma.

Aim: To construct a gene modified hepatocellular carcinoma (HCC) specific EGFP expression vector regulated by abbreviated cis-acting element of AFP gene.

Methods: The minimal essential DNA segments of AFP gene enhancer and promoter were synthesized through PCR from Genome DNA of HepG2 cells. Gene fragments were then cloned into the multiple cloning site of non-promoter EGFP vector pEGFP-1.