Use Of Anti-tumor Therapy Research Articles

The effect-enhancing and toxicity-reducing activity of Hypericum japonicum Thunb. extract in murine liver cancer chemotherapy

Chinese herbs are potential sources of antitumor drugs with immunoregulatory activity and few adverse effects. In the present study, we investigated whether the Hypericum japonicum Thunb. (HJT) extract enhanced the efficacy of 5-fluorouracil (5-FU) treatment in murine liver tumor xenografts and reduced toxicity of chemotherapy in hepatoma H22-bearing mice. Tumor weight and inhibition rate, thymus and spleen indices, as well as white blood cell (WBC) count were calculated. The phagocytic function of macrophages was assessed by observing peritoneal macrophages phagocytized chicken red blood cells (RBC). Body weight and toxic reactions of the chemotherapeutic and life prolongation rate were investigated in the mice. Results demonstrated that the HJT extract significantly enhanced the tumor inhibition rate of 5-FU, improved the immune function, reduced the toxic effects and prolonged the survival time in the tumor-bearing mice. Taken together, these results indicated that the HJT extract has a synergistic tumor-inhibiting effect with 5-FU, is able to reduce the toxic side effects and is likely to be safe and efficacious for use in antitumor therapy.

In Vitro and In Vivo Antitumor Activity of Scutellaria barbate Extract on Murine Liver Cancer

In the present study, we investigated the in vitro and in vivo antitumor effects of crude extract of Scutellaria barbate (CE-SB) on mouse hepatoma H22 cells. The MTT assay was used to determine the growth inhibition of H22 cells in vitro. The in vivo therapeutic effects of CE-SB were determined using H22 tumor bearing mice. Besides, the body weight, tumor weight, thymus index and spleen index of H22 bearing mice were also measured. The tumor inhibitory rate (IR) was calculated according to the mean weight of tumor (MWT). The phagocytotic function of macrophages was examined by observing peritoneal macrophages phagocytize chicken RBC. The results showed that CE-SB could inhibit the growth of hepatoma H22 Cells in vitro and in vivo. Furthermore, CE-SB could improve immune function of H22 tumor bearing mice. Together these results indicate that CE-SB has antitumor activity and seems to be safe and effective for the use of anti-tumor therapy.

Intratumoral CC Chemokine Ligand 5 Overexpression Delays Tumor Growth and Increases Tumor Cell Infiltration

Chemokines participate in the antitumor immune response by regulating the movement and positioning of lymphocytes as well as effector functions and may thus be candidates for use in antitumor therapy. To test whether CCL5, a chemokine involved in the recruitment of a wide spectrum of immunocompetent cells, can control tumor growth, we forced its expression at mouse tumor sites. Tumor growth was reduced in mice with s.c. syngeneic CCL5-EL-4 compared with EL-4-injected mice, whereas both reduced tumor growth and incidence were observed in mice with OVA-expressing EG-7 transfected with CCL5 compared with EG-7-injected mice. Significant antitumor effects were observed soon after intratumoral injection of DNA plasmid coding for chimeric CCL5-Ig. Importantly, quantitative RT-PCR assays showed that the amount of CCL5 expression at the tumor site determined the effectiveness of the antitumor response, which was associated with infiltration of increased numbers of NK, CD4, and CD8 cells at the tumor site. This effect was lost in mice deficient for T/B lymphocytes (RAG-2 knockout) or for CCR5 (CCR5 knockout). Together, these data demonstrate the antitumor activity of intratumoral CCL5 overexpression, due to its recruitment of immunocompetent cells, and the potential usefulness of chimeric CCL5-Ig DNA as an agent in cancer therapy.

Laser-beam-triggered microcavitation: a novel method for selective cell destruction.

We describe a new method of cell destruction that may have potential for use in antitumor therapy. Cells are loaded by phagocytosis with microparticles (<1 microm) and irradiated with short laser pulses. Absorption of laser energy by the microparticles causes localized vaporization of the fluid surrounding the microparticles, leading to the generation of transient vapor bubbles (microcavitation) around the microparticles. Using cultures of bovine aortic endothelial cells, we demonstrate that induction of intralysosomal microcavitation is an efficient, rapid and selective method of cell killing that is dependent on the number of microparticles, the number of laser pulses, and the fluence of the laser pulses. Cell killing by microcavitation is a very selective process that is restricted to cells containing microparticles, leaving other cells unaffected. Intracytoplasmic release of lysosomal hydrolases is, in part, responsible for cell death, because the protease inhibitors E64d and TLCK diminished cell killing. Using the broad-specificity caspase inhibitor Z-VAD-fmk, we determined that lysosomal hydrolases could induce apoptosis in a caspase-independent manner. We also examined the possibility of microcavitation-induced delayed effects in the cells that survived the treatment. Using flow cytometry, we determined that there was no delayed cell death between 1 and 4 days after microcavitation. Moreover, we did not observe changes in the cell cycle, in expression of the proteins BCL2, HSP70 and HSP27, or in PARP degradation. In conclusion, microcavitation induces rapid and specific cells death (limited only to cells containing microparticles), without producing delayed effects among the surviving cells.

Interleukin-7 and lymphopoiesis: biological and clinical implications.

IL-7 was identified in 1988 following an intensive search for bone-marrow stromal cell growth factors involved in early steps of B-cell genesis [1]. The role of IL-7 has since been expanded to include functions as a thymocyte growth factor and a pre-T-cell differentiation factor, as well as an activation factor for monocytes and macrophages, NK cells, cytolytic T lymphocytes (CTL’s), and lymphokine-activated killer cell (LAK) activity. Several preclinical studies in mice predict that IL-7 may be of use in antitumor therapy and acceleration of lymphoid recovery in lymphopenic patients. In addition, IL-7 appears to hold promise in enhancing antimicrobial responses. This chapter describes in detail the current status of IL-7 as a regulator of lymphopoiesis and effector cell function, and the potential therapeutic implications of the IL-7 preclinical studies performed in mice.KeywordsAcute Lymphoblastic LeukemiaGamma DeltaThymocyte ProliferationStimulate Tyrosine PhosphorylationFetal ThymocyteThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.