High-efficacy targeting of colon-cancer liver metastasis withSalmonella typhimuriumA1-R via intra-portal-vein injection in orthotopic nude-mouse models

Abstract

Liver metastasis is the main cause of colon cancer-related death and is a recalcitrant disease. We report here the efficacy and safety of intra-portal-vein (iPV) targeting of Salmonella typhimurium A1-R on colon cancer liver metastasis in a nude-mouse orthotopic model. Nude mice with HT29 human colon cancer cells, expressing red fluorescent protein (RFP) (HT29-RFP), growing in the liver were administered S. typhimurium A1-R by either iPV (1×104 colony forming units (CFU)/100 μl) or, for comparison, intra-venous injection (iv; 5×107 CFU/100 μl). Similar amounts of bacteria were delivered to the liver with the two doses, indicating that iPV delivery is 5×103 times more efficient than iv delivery. Treatment efficacy was evaluated by tumor fluorescent area (mm2) and total fluorescence intensity. Tumor fluorescent area and fluorescence intensity highly correlated (p<0.0001). iPV treatment was more effective compared to both untreated control and iv treatment (p<0.01 and p<0.05, respectively with iPV treatment with S. typhimurium arresting metastatic growth). There were no significant differences in body weight between all groups. The results of this study suggest that S. typhimurium A1-R administered iPV has potential for peri-operative adjuvant treatment of colon cancer liver metastasis.

Intra-arterial administration of tumor-targetingSalmonella typhimuriumA1-R regresses a cisplatin-resistant relapsed osteosarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model

“…21,37 We previously reported the efficacy and safety of intra-portal-vein (iPV) targeting of S. typhimurium A1-R on colon cancer liver metastasis in a nude-mouse orthotopic model. 38 In the present report, we demonstrate the high efficacy of intra-arterial (i.a.) administration of S. typhimurium A1-R on the CDDP-resistant, recurrent osteosarcoma in the PDOX model.…”

<p>Analysis of <em>Salmonella typhimurium</em> Protein-Targeting in the Nucleus of Host Cells and the Implications in Colon Cancer: An in-silico Approach</p>

“…Obligate and invasive nature of S. typhimurium coupled with detection of strong inter-strain lateral gene transfer frequency suggests potential involvement of S. typhimurium lateral gene transfer in colon cancer etiology. 21,32 The chaperones contain cancer antagonist properties by working as genetic buffers, which stabilizes the usual phenotype. 27 Therefore, the alteration in chaperones can act as a potential factor for cancer development.…”

Harnessing Omics Approaches on Advanced Preclinical Models to Discovery Novel Therapeutic Targets for the Treatment of Metastatic Colorectal Cancer

“…In particular, the Hoffman’s group developed orthotopic models of mCRC via the implantation of human tumor tissues into the serosa of the cecum of immunosuppressed mice. The growth of primary tumors and spontaneous metastases were visualized by the use fluorophore-conjugated anti-CEA antibodies [ 48 ] or by transfecting cells with green or red fluorescence protein [ 49 , 50 ]. This technology represents a very potent tool for the identification of the anticancer activity of new therapeutic approaches.…”