Biomedical subjects

Leland J Soto

Publications and source records attributed to Leland J Soto.

4 recordsLinked to original sources

PubMed2005

Attenuated Salmonella typhimurium invades and decreases tumor burden in neuroblastoma.

INTRODUCTION: We have previously shown that Salmonella elicits an antitumor response against hepatic adenocarcinomatous metastases. In vitro studies have demonstrated both intracellular invasion and proliferation of Salmonella within cultured neuroblastoma cells. We sought to demonstrate in vivo invasion, proliferation, and a potential antitumor response. METHODS: A murine model for retroperitoneal neuroblastoma was established with viable neuroblastoma cells. A green fluorescent protein (GFP--Clontech, Palo Alto, CA) gene was inserted into our attenuated Salmonella species via electroporation. Fourteen days after retroperitoneal injection, the Salmonella typhimurium-pGFP construct was administered and studied. In separate experiments, the antitumor effect against neuroblastoma was studied in controls, Salmonella lacking an interleukin 2 (IL-2) gene (Sal-NG), and Salmonella containing an IL-2 gene (Salmonella-pIL2 ). RESULTS: Consistent with previous reports, 74% of mice injected were found to have recognizable tumors. Salmonella was present within tumor cells. Average tumor volumes for control, Sal-NG, and Salmonella-pIL2 mice were 2024.3, 749.5, and 332.4 mm3 , respectively (P < .0001). Tumor weights for control, Sal-NG, and Salmonella-pIL2 mice were 2.218, 0.880, and 0.377 g, respectively (P < .0001). CONCLUSIONS: Attenuated Salmonella species can now be tracked via fluorescent microscopy within tumor cells. Furthermore, an 84% reduction in tumor burden was observed in those animals gavage fed Salmonella with the IL-2 gene.

Animals↗

PubMed2004

Preferential proliferation of attenuated Salmonella typhimurium within neuroblastoma.

BACKGROUND/PURPOSE: Attenuated Salmonella typhimurium, a facultative intracellular parasite that colonizes the liver, has been shown to accumulate within extrahepatic malignancies. The authors sought to define a mechanism for attenuated Salmonella accumulation within cancer cells compared with hepatocytes. METHODS: Invasion and intracellular proliferation of attenuated Salmonella was assessed through an in vitro assay performed on neuroblasoma, osteosarcoma, hepatoma, and colon adenocarcinoma cell lines and compared with freshly isolated mouse hepatocytes. RESULTS: The efficiency of attenuated S typhimurium invasion into hepatocytes was greater than any malignant cell line (3.8 v 0.46; P <.04). However, the intracellular proliferation of the bacteria was most abundant within neuroblastoma, exceeding the proliferation within hepatocytes (14.3 v 6.2; P <.01). CONCLUSIONS: Attenuated S typhimurium may prove to be an effective in vivo immunotherapy for the local delivery of therapeutic proteins to neuroblastoma.

Adenocarcinoma↗

PubMed2003

Attenuated Salmonella typhimurium prevents the establishment of unresectable hepatic metastases and improves survival in a murine model.

PURPOSE: The authors investigated the utility of attenuated Salmonella typhimurium for preventing the establishment of hepatic metastases in a murine model. METHODS: A single, oral 10(8) cfu dose of attenuated S typhimurium was given 8 days before the establishment of a model of unresectable hepatic metastases. Animals were assessed for hepatic tumor number and volume, hepatic lymphocyte population analysis, and survival. RESULTS: Pretreatment with Salmonella provided a 10-fold reduction in hepatic tumor burden compared with saline-treated controls. The antitumor effect is associated with markedly elevated natural killer (NK), CD8+ and CD4+ hepatic lymphocytes. Pretreatment with Salmonella provided a 90-day survival rate of 30%, whereas control animals were dead by 30 days. All long-term survivors were devoid of hepatic tumor. CONCLUSIONS: Attenuated S typhimurium effectively prevents the establishment of hepatic metastases in a murine model, providing a clear survival benefit. Thus, it may represent a novel form of in vivo immunotherapy for the prevention of hepatic metastases for patients with locally advanced colorectal cancer.

Adenocarcinoma↗

PubMed2003

Rectal impalement: a case review.

Pediatric impalement injuries to the rectum are rare, and delays in diagnosis can be life threatening. We report the case of a young girl who was accidentally impaled on a dive stick. A review of historical aspects of rectal trauma and current management techniques are discussed. Rectal injuries in the pediatric population most often result from accidental impalement, sexual abuse, or blunt trauma. In contrast, most rectal injuries in adults are caused by missile wounds. Moreover, because rectal injury is fairly uncommon in children, physicians evaluating patients may miss signs of serious injury. Signs of external trauma may be minimal when rectal perforation exists, so delays in diagnosis are not uncommon.

Child, Preschool↗