Effect of interstitial chemotherapy with ricin temperature-responsive gel for anti-breast cancer and immune regulation in rats.

OBJECTIVE: To explore the effect of ricin temperature response gel on breast cancer and its regulatory effect on immune function in rats. METHODS: Ricin was purified by chromatography and identified by immunoblotting. The rat subcutaneously transplanted breast cancer model was established. Forty model rats with a tumor diameter of about 3.0 cm were subjected to the study. They were randomized into four groups equally: the model group and three treated groups (blank gel, ricin, ricin-gel) were administered with blank gel, ricin, and ricin temperature response gel via percutaneous intratumor injection, respectively. The tumor was isolated 10 days later for the estimation of tumor inhibition rate (TIR) by weighing, pathologic examination, and detection of tumor apoptosis-associated genes bcl-2 and bax with semiquantitative RT-PCR. Also, peripheral blood was obtained to test T-lymphocyte subsets, the killing function of lymphocytes, and the contents of tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2). The outcomes were compared between groups. RESULTS: The TIR in the ricin-gel group was 61.8%, with the pathologic examination showing extensive tumor tissue necrosis. Compared with the model group, after ricin temperature response gel treatment, bcl-2 expression was down-regulated, bax expression was up-regulated, CD4+ lymphocytes and CD4+/CD8+ ratio in peripheral blood were increased, the killing function of lymphocytes was enhanced, and the contents of TNF-α and IL-2 were elevated (P < 0.05 or P < 0.01). CONCLUSION: Intratumor injection of ricin temperature-responsive gel showed significant antitumor effect on breast cancer and could enhance the immune function in the tumor-bearing rat.

US-guided interstitial chemotherapy using paclitaxel temperature-responsive gel for breast cancer treatment in rat.

INTRODUCTION: This study aims to investigate the therapeutic effect of paclitaxel temperature-responsive gel (PTRG) for interstitial chemotherapy on breast cancer, and to explore a new minimally invasive treatment for breast cancer. MATERIALS AND METHODS: Breast cancer models were induced in rats using subcutaneous transplantation of tumor cells. The rats were then divided into control, paclitaxel injection, gel injection and paclitaxel-gel (PG) group. Following treatment, all animals were checked regularly by ultrasonography to observe changes in the tumors. Biopsy tumor tissues were processed for histopathological examination, and apoptotic index was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling method. In addition, blood cell count and liver transaminase activity were monitored, and the survival time of rats with cancer recorded. RESULTS: Rats in PG group exhibited liquefaction necrosis of tumors. Ninety days after the experiment, four rats exhibited complete extinction of tumors, indicating full recovery. Pathological examination revealed that the tumor tissues in these rats were mostly necrotic, and the apoptotic index of tumor cells increased markedly compared to PI group. Also, the red blood cell, hemoglobin and white blood cell levels declined significantly in the PI group compared with PG group, while glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase activities significantly increased. Meanwhile, no toxicity due to treatment was observed in PG group. CONCLUSION: Interstitial chemotherapy mediated by PTRG appeared to be a safe and effective treatment for breast cancer in rats. It might have clinical applications for treating human breast cancer.

[Effects of interstitial chemotherapy using thermosensitive gel-coated ricin on hepatoma H22-bearing mice].

OBJECTIVE: To explore the efficacy and feasibility of interstitial chemotherapy using thermosensitive gel-coated ricin in hepatoma H22-bearing mice. METHODS: Ricin was purified by chromatography method. The purified ricin was identified by Western blot assay and the purity was determined by high-performance liquid chromatography. BALB/c mice were inoculated subcutaneously in right flank with hepatoma H22 cells. When the tumor size reached about 1.0 cm in diameter, 40 mice were randomly divided into untreated group, thermosensitive gel group, ricin group and thermosensitive gel-coated ricin group. Mice in each group were administered different agents by percutaneous intratumoral injection, including normal saline, thermosensitive hydrogel, ricin and thermosensitive gel-coated ricin. Fifteen days after treatment, the tumors were removed to calculate inhibition rate of tumor growth. The tumor tissues were made into pathological sections to perform histopathological examination. The ultrastructure of tumor tissue was examined by electron microscope examination as well. Blood was collected to detect the hepatic and renal functions. The caspase-3 activity of tumor tissue was determined by using zymologic method with a spectrophotometer. RESULTS: After intratumoral therapy, tumor weight in the thermosensitive gel-coated ricin group was lower than that in the untreated group, with a tumor growth inhibition rate of 71.31%. No obvious hepatic or renal toxicities were detected after thermosensitive gel-coated ricin treatment. Histopathologic observation of the tumor tissue showed massive necrosis and typical apoptosis phenomena, including chromatin margination and apoptotic body. Meanwhile, thermosensitive gel-coated ricin resulted in a significant increase in the caspase-3 activity as compared with the untreated group and the ricin group (P<0.01, P<0.05). CONCLUSION: The above findings indicate that intratumoral therapy with thermosensitive gel-coated ricin has strong antitumor effect and can obviously lessen systemic toxicity, which may provide an effective and feasible method for hepatocellular carcinoma treatment.