Objective: To investigate the role and mechanism of histamine in regulation of C57BL/6 mice spleen derived LAK activity in vivo. Methods: The C57BL/6 mice carrying B16 pulmonary metastatic melanoma were treated with LAK/IL 2/histamine therapy or LAK/IL 2 therapy with the aim of evaluating both anti tumor responses in vivo. Results: It was found that the addition of histamine effectively potentiated the anti metastatic effect produced by LAK/IL 2 therapy and induced regression of NK resistant B16 pulmonary metastatic melanoma. Survival period was significantly prolonged in mice receiving LAK/IL 2/histamine as compared with LAK/IL 2 therapy alone. The effect of histamine was completely blocked by H 2 R antagonist ranitidine, and mimicked by dimaprit, a H 2 R agonist. Conclusion:Histamine, via specific activation of H 2 R, may be an important regulator of LAK cells activity; histamine and LAK/IL 2 synergistically induce more potent antitumor efficacy in vivo .

To explore the effect of IL-33 on various tumor types,exogenous injection of recombinant mouse IL-33 protein (mIL-33) was used to study the efficacy of different subcutaneous tumor-bearing mouse models. In this study,mIL-33 has been found to significantly inhibit the growth of liver,lung,gastric,prostate,and colon cancers. However,the inhibition of tumor growth by mIL-33 was not completely consistent in different types of tumor. A lower dose of mIL-33 (10 μg/kg) significantly inhibited tumor growth in subcutaneous tumor-bearing mice of liver,lung,and gastric cancers,while a higher dose of mIL-33 (90 μg/kg) was required to exert the corresponding antitumor effect in subcutaneous tumor-bearing mouse models with prostate and colon cancers. In addition,the growth inhibitory effect of mIL-33 on subcutaneous tumors of colon cancer was also correlated with the duration of administration and the stage of tumor progression. The results of this study indicate that mIL-33 significantly inhibits the growth of a variety of tumors,suggesting that IL-33 might be an effective target for tumor treatment.

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development