Autogenous hepatic tissue transplantation into the omentum in a novel ectopic liver regeneration murine model.

BACKGROUND: Liver regeneration involves hyperplasia and hypertrophy of hepatic cells. The capacity of macroscopic liver tissue to regenerate in ectopic sites is unknown. We aim to develop a novel in vivo model of ectopic liver survivability and regeneration and assess its functionality. METHODS: Adult male Sprague-Dawley rats (n = 23) were divided into four groups: (1) single-stage (SS) group, wedge liver resection was performed, and the parenchyma was directly implanted into the omentum; (2) double-stage (DS) group, omentum pedicle was transposed over the left hepatic lobe followed by wedge liver resection along with omental flap; (3) Biogel + DS group, rats received intraperitoneal injection of inert polymer particles prior to DS; (4) Biogel + DS + portal vein ligation (PVL) group, Biogel + DS rats underwent subsequent PVL. Hepatobiliary iminodiacetic acid scintigraphy assessed bile excretion from ectopic hepatic implants. RESULTS: Histologically, the scores of necrosis (P < 0.001) and fibrosis (P = 0.004) were significantly improved in rats undergoing DS procedure (groups 2, 3, and 4) compared with the SS group. Biogel rats (Biogel + DS and Biogel + DS + PVL) demonstrated statistically increased scores of bile duct neoformation (P = 0.002) compared to those without the particles (SS and DS). Scintigraphy demonstrated similar uptake of radiotracer by ectopic hepatic implants in groups 2, 3, and 4. CONCLUSIONS: Omental transposition provided adequate microcirculation for proliferation of ectopic hepatic cells after liver resection. Inert polymers enhanced the regeneration by promoting differentiation of new bile ducts. The ectopic hepatic implants showed preserved function on scintigraphy. This model provides insights into the capacity of liver parenchyma to regenerate in ectopic sites and the potential as therapeutic target for cell therapy in end-stage liver disease.

A true orthotopic gastric cancer murine model using electrocoagulation.

BACKGROUND: Orthotopic mouse models of human gastric cancer represent an important in vivo tool for testing chemotherapeutic agents and for studying intraluminal factors. Currently, orthotopic mouse models of gastric cancer require an operative procedure involving either injection or implantation of tumor cells in stomach layers. The resultant tumor does not grow from the stomach's mucosal surface, so it does not mimic the human disease process. STUDY DESIGN: A low-dose gastric mucosal coagulation was done transorally in the body of stomach using a specially designed polyethylene catheter in 16 female severe combined immunodeficient mice. This was followed by the instillation of SNU-16 human gastric cancer tumor cells (1 × 10(6) cells). Five mice each were euthanized at 1 and 2 months, and 6 mice were euthanized at 3 months. Three control mice underwent electrocoagulation alone and 3 mice underwent cell line instillation alone. RESULTS: Tumors were detected in 11 of 16 experimental mice, but not in the control mice. Tumors were noted in mice at 1 month. Over time, there was an increase in tumor growth and metastasis to lymph nodes and surrounding organs. Histopathologic evaluation showed that the tumors grew from the gastric mucosa. CONCLUSIONS: Our model is easy to create and overcomes the limitations of the existing models, as the tumor arises from the stomach's mucosal layer and mimics the human disease in terms of morphology and biologic behavior. This is the first report of a true orthotopic gastric cancer murine model. This model opens new doors for additional studies that were not possible earlier.

Intratumoral acetic acid injection eradicates human prostate cancer tumors in a murine model.

INTRODUCTION: To treat localized prostate cancer without substantial morbidity, an ideal treatment would be an effective local therapy with minimal morbidity. Direct injections have been used to treat benign prostatic hyperplasia without major complications, but in limited cases. We evaluated the local oncotoxic effects of acetic acid in a prostate cancer xenograft murine model. MATERIALS AND METHODS: PC3 and LNCaP human prostate cancer cell lines were used to grow subcutaneous tumors in SCID mice. For each cell line, 14 mice underwent intratumor injection with 25% acetic acid (0.05 ml/100 cm3 of tumor) after the tumor was >300 mm3. Post-treatment one mouse/group was euthanized after 2 h, 24 h, 1 and 2 weeks; remaining mice (n = 10) were killed at 120 days. Control mice (8/group) were euthanized after they met the humane criteria for tumor burden and overall health. RESULTS: Tumor necrosis was noted immediately post-injection; by 24 h, ulceration and crusting of overlying skin were noted, which healed into scars by 23 ± 5 days. Histological examination showed tumor degeneration and necrosis with blood vessel obstruction. Ten treated mice in both groups survived for 120 days, which was much longer than the mean survival of PC3 (40 ± 9 days) and LNCaP (56 ± 10) control mice. CONCLUSIONS: Direct injection of acetic acid successfully eradicated both tumors. This treatment option could potentially be used in humans for treatment of early localized prostate cancer and nonoperative management of locally advanced cases. This is the first report of successful local chemical therapy for prostate cancer.

A novel nonoperative orthotopic colorectal cancer murine model using electrocoagulation.

BACKGROUND: Orthotopic mouse models of human colorectal cancer represent an important in vivo tool for testing chemotherapeutic agents and studying intraluminal factors that may alter the growth of cancers. Currently the orthotopic mouse models of colorectal cancer require either an operative procedure or creation of colitis to implant the cancer cells in rectum. We have developed a nonoperative, minimally invasive technique to create a true orthotopic colon cancer mouse model. STUDY DESIGN: We used human (LS 174T and HT-29) and murine (CRL-2638 and CRL-2639) colon cancer cell lines. Low-dose mucosal coagulation was performed transanally using a specially designed electrode at 1 to 3 predetermined points, 2 to 3 cm from the anus, followed by a transanal instillation of tumor cells (1 × 10(6) cells) in 12 female nude or severe combined immunodeficiency disease mice for each of the 4 groups (n = 48, plus 16 controls). Mouse colonoscope (Coloview) and microCT were used to follow tumor growth. Four mice from each group were euthanized at 1, 2, and 3 weeks. RESULTS: Tumors were detected in 12 of 12 of the CRL-2638, 11 of 12 of the CRL-2639, 7 of 12 of the HT-29 and 12 of 12 mice in the LS 174T groups. Histopathologic evaluation showed that the tumors grew from the colonic mucosa. CRL-2638 and LS 174T exhibited better implantation, faster tumor growth, larger tumor volume, and earlier metastases. MicroCT detected tumors larger than 3 mm, and the colonoscopy detected tumors larger than 1 mm. CONCLUSIONS: Our mouse model is minimally invasive and easy to create and overcomes the limitations of existing models while mimicking the human disease in terms of morphology and biologic behavior. This model opens the doors for colon cancer oncologic studies in an animal model that were previously not possible.