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Objective: This study aimed to ascertain what should be considered in the "Guideline for Clinical Trials with Herbal Medicinal Products for Liver Cancer," by analyzing existing guidelines and clinical trials. Methods: Committee for the development of a guideline, consisting of 6 Korean medicine doctors, reviewed guidelines and clinical trials on using herbal medicine for treating liver cancer. The trials were analyzed in terms of inclusion and exclusion of participants, intervention, comparators, outcomes, and trial design. We then compared the results of our analysis with the guidelines to identify issues we must to consider when following the "Guideline for Clinical Trials with Herbal Medicinal Products for Liver Cancer." Several guidelines for antitumor agents and clinical trials on herbal medicine were obtained from the Ministry of Food and Drug Safety homepage, etc. The search terms were as follows: "liver neoplasms"; "herbal medicine"; "medicine, Korean traditional"; and "medicine, Chinese Traditional.". Results: Ten articles were obtained from pubmed and Embase. There was no guideline for clinical trials on using herbal medicine for treating liver cancer. All the participants in the reviewed articles had primary liver cancer, and the type of intervention varied (e.g., decoction, patches, and capsules. The comparators included placebos and conventional treatments such as chemotherapy. The outcome assessment methods were tumor response, quality of life, survival, and liver function tests. Adverse events occuring during the trial were also evaluated. Conclusion: Findings were derived by reviewing existing guidelines and comparing them with clinical trials on liver cancer and herbal medicinal products. These results will be utilized in the development of the "Guideline for Clinical Trials with Herbal Medicinal Products for Liver Cancer."

We show that Rap2, a member of the Ras GTPase family, positively regulates Activin/Nodal signaling activity by controlling the trafficking of its receptors. In the absence of ligand activation, Rap2 directs internalized Activin/Nodal receptors into a recycling pathway, thereby preventing their degradation and maintaining their levels on the cell surface. Upon ligand activation, Rap2 no longer promotes receptor recycling but delays its turnover. In both cases, Rap2 contributes to upregulation of signaling activity by antagonizing Smad7. In addition, we found that the efficiency of Activin/Nodal receptor recycling is different between dorsal and ventral halves of Xenopus early embryo, which results from the asymmetric expression of Rap2 and Smad7. Consequently, they regulate cell responsiveness to ligands and the spatiotemporally dynamic activation of Smad2 along the dorsoventral axis of the embryo. Therefore, these findings suggest a molecular basis for the regulation of signaling activity and embryonic patterning by Activin/Nodal receptor trafficking.

Activin/Nodal signaling is essential for germ-layer formation and axial patterning during embryogenesis. Recent evidence has demonstrated that the intra- or extracellular inhibition of this signaling is crucial for ectoderm specification and correct positioning of mesoderm and endoderm. Here, we analyzed the function of Xenopus serum response factor (XSRF) in establishing germ layers during early development. XSRF transcripts are restricted to the animal pole ectoderm in Xenopus early embryos. Ectopic expression of XSRF RNA suppresses mesoderm induction, both in the marginal zone in vivo and caused by Activin/Nodal signals in animal caps. Dominant-negative mutant or antisense morpholino oligonucleotide-mediated inhibition of XSRF function expands the expression of mesendodermal genes toward the ectodermal territory and enhances the inducing activity of the Activin signal. SRF interacts with Smad2 and FAST-1, and inhibits the formation of the Smad2-FAST-1 complex induced by Activin. These results suggest that XSRF might act to ensure proper mesoderm induction in the appropriate region by inhibiting the mesoderm-inducing signals during early embryogenesis.