Research Progress on Anti-tumor Mechanism of Formononetin / 中国实验方剂学杂志

Formononetin is a kind of plant isoflavones extracted from medicinal herbs such as Trifolium pratense，Astragalus membranaceus and Spatholobi Caulis have shown that formononetin has strong anti-tumor biological activity，and can be used as an anti-tumor drug in the treatment of various malignant tumors. Many studies so far have shown that formononetin can inhibit cell proliferation，induce cell apoptosis，inhibit cell migration and invasion，and induce cell cycle arrest on tumors through a variety of molecular mechanisms and pathways. These antitumor activities can be observed in cells of various tumors such as breast cancer，colorectal cancer，prostate cancer，bladder cancer and lung cancer in trials and animal models. Examples of these effects include triggering the generation of reactive oxygen species （ROS），regulating phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin（PI3K/Akt/mTOR） and Mitogen-activated protein kinases（MAPK） signaling pathways，inhibiting the activation of tyrosine kinase（JAK1 and JAK2 ）and nonreceptor tyrosine kinase（c-Src），and regulating cytokeratin 19（CK19），matrix metalloproteinases（MMP），microRNA-21（miR-21），lamin A/C antibody（Lamin A/C），expression of Cyclin D1 and Cyclin E1. In addition， the anti-tumor effects of formononetin derivatives were reviewed in this paper. By modifying the chemical structure of formononetin，many related derivatives have been obtained. Experimental results have shown that some derivatives of formononetin have stronger anti-tumor activity and lower cytotoxicity，but the related molecular mechanism of action still needs to be explored further in-depth. In conclusion，formononetin and its derivatives may become potential anti-tumor drugs.

Research Progress on Lichongtang in Treatment of Uterine Leiomyoma / 中国实验方剂学杂志

Uterine leiomyoma （UL）， the most common benign tumor of the reproductive system in women of childbearing age， is characterized by clinical symptoms such as increased menstrual flow， prolonged menstrual period， breast tenderness，backache， lower abdominal pain and mass in the lower abdomen. With the continuous progress of modern society， the age of women's marriage and childbirth is gradually pushed back， which to a certain extent has led to an increase in the probability of modern women suffering from UL. Relevant literature shows that the incidence of UL is about 70%， and 25%-50% of the patients have clinical symptoms， seriously endangering women's physical health. The prevention and treatment of UL by modern medicine is currently limited to two aspects： drug control of estrogen and progesterone levels and surgical removal. Traditional Chinese medicine（TCM）has shown obvious advantages in improving the clinical symptoms of UL patients， with very broad application prospects as it can regulate body's Qi and blood on the basis of syndrome differentiation， treatment and overall concepts. Lichongtang， as a famous TCM prescription for replenishing Qi， activating blood and removing blood stasis， was created by ZHANG Xi-chun， a famous Chinese medicine doctor in the Qing dynasty， and recorded in the Records of Tradition Chinese and Western Medicine in Combination. It is widely used in the field of gynecological diseases in clinical practice. Studies have shown that Lichongtang is effective in treating UL. Clinical observations show that Lichongtang can significantly relieve the clinical symptoms of UL patients such as prolonged menstrual period， dysmenorrhea， waist and abdomen swelling and irregular vaginal bleeding， with the characteristics of stable curative effect， high safety， less side effect and low recurrence rate. The experimental results show that Lichongtang has a comprehensive regulatory effect on UL through inhibiting the proliferation of UL cells and inducing apoptosis， reducing serum estrogen and progesterone level， regulating the apoptosis pathway of tumor cells， and promoting the degradation of extracellular matrix（ECM）. After retrieval in PubMed， CNKI and other databases， the authors made a review by summarizing the theories， clinical efficacy and action mechanisms of Lichongtang in the treatment of UL， in order to provide reference for the follow-up in-depth study of pharmacological mechanism of Lichongtang and its further clinical application and promotion.

Concurrent chemoradiotherapy combined with enteral nutrition support: a radical treatment strategy for esophageal squamous cell carcinoma patients with malignant fistulae.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) significantly increases the survival rate of esophageal squamous cell carcinoma (ESCC) patients with malignant fistulae. Recent clinical evidence has shown the benefits of enteral nutrition for malnourished cancer patients. In this study, we aimed to validate that, with the support of enteral nutrition, ESCC patients who develop malignant fistulae might be able to complete CCRT and achieve long-term survival. METHODS: We reviewed the medical records of 652 patients with ESCC who received definitive CCRT at Sun Yat-sen University Cancer Center between January 2010 and December 2012. Treatment outcome and toxicity were retrospectively evaluated in 40 ESCC patients with malignant fistulae. All the 40 patients were treated with CCRT and evaluated by clinical nutritionists using nutrition risk screening (NRS) before, during, and after treatment. Twenty-two patients received a nasogastric tube, and 18 underwent percutaneous endoscopic gastrostomy feeding. The median energy intake was 2166 kcal/day. Treatment response was evaluated at 3 months after the completion of CCRT. RESULTS: With a median follow-up of 18 months (range, 3-39 months), patients' 1-year overall survival (OS) rate was 62.5%, and the estimated OS time was 25.5 months. Univariate analysis showed that the NRS score (P = 0.003), increase in NRS score (P = 0.024), fistula closure (P = 0.011), and response to treatment (P < 0.001) were significantly associated with OS. Multivariate analysis showed that tumor response (P = 0.044) and increase in NRS score (P = 0.044) were independent predictors of OS. Grade 3 vomiting was observed in 8 patients (20.0%), grade 3 neutropenia was observed in 11 patients (27.5%), and grade 3 cough was observed in 13 patients (32.5%); 2 patients (5.0%) died of massive bleeding during treatment. CONCLUSIONS: CCRT combined with enteral nutrition support is effective for ESCC patients with malignant fistulae. Patients have an increased potential to be cured, especially those who experience complete response and have an increase in NRS score. Careful observation and nutrition support are required for patients with advanced T-category ESCC who undergo CCRT.

[Effect of cellular immune supportive treatment on immunity of esophageal carcinoma patients after modern two-field lymph node dissection].

BACKGROUND & OBJECTIVE: Cellular immunity suppression is marked in patients with esophageal carcinoma, which may be resulted temporarily from surgical injury. This study was to evaluate the effect of cellular immune supportive treatment on cellular immunity of patients with esophageal carcinoma. METHODS: A total of 60 patients with thoracic esophageal carcinoma, received two-field dissection, were randomized into control group and trial (immune supportive treatment) group. The patients in trial group were injected with Shenqi injection after operation; the patients in control group received no immune supportive treatment. Peripheral blood samples were obtained before operation, and 3 and 9 days after operation. AgNOR (argyrophilic nucleolar organizer regions) activity in peripheral blood T lymphocytes was measured by tumor immune microphotometry. T cell subsets were measured by flow cytometry. RESULTS: The proportions of CD3+CD4+ and CD4+/CD8+ cells were significantly higher in trial group than in control group at 3 days after operation (P < 0.05). The amount of AgNOR and proportions of CD3+, CD3+CD4+, CD4+/CD8+, and CD4+CD25+ cells were significantly higher in trial group than in control group at 9 days after operation (P < 0.05). There was no significant difference in 1-year survival rate between the 2 groups (P > 0.05). CONCLUSION: Shenqi injection could obviously improve cellular immunity of the esophageal carcinoma patients after modern two-field dissection.