Cancer Associated Cells in Tumor Microenvironment of Esophageal Carcinoma： A Review / 中国实验方剂学杂志

Esophageal carcinoma is one of the malignant tumors with a high mortality rate， accounting for nearly 570，000 cancer deaths worldwide annually， and this number is increasing year by year. In recent years， despite the continuous improvement of treatment programs for esophageal carcinoma， the overall five-year survival rate of esophageal carcinoma is still less than 20% due to the development of drug resistance and the tolerance of patients during the treatment process. Tumor microenvironment （TME） is composed of various cells and related components with tumor cells as the core and featured by hypoxia， acidosis， chronic inflammation and immunosuppression， which plays an important role in the progression of tumors. Studies have found that tumor-associated fibroblasts， tumor-associated macrophages， myeloid-derived suppressor cells and regulatory T cells in TME can promote the proliferation， migration， invasion， and lymph node metastasis of cancer cells by secreting cytokines and activating pro-inflammatory pathways， and promote cancer progression by inducing the drug resistance of cancer cells and evading immunosuppression. Because cancer-associated cells in TME are genetically more stable than cancer cells， have fewer mutations and have lower chance of drug resistance， targeting cancer-associated cells in TME by regulating TME is a new research direction of cancer therapy. Traditional Chinese medicine has the advantages of multi-component and multi-target. It can participate in the regulation of TME through multiple ways， reduce the number of cancer-associated cells in TME， inhibit crosstalk between TME and cancer cells， and restore immune cell function. It is an important source for the regulation of TME and the research and development of drugs targeting cancer-associated cells in TME. In this paper， the role of cancer-associated cells in the TME of esophageal cancer and the current application of traditional Chinese medicine targeting cancer-associated cells in TME are reviewed， so as to provide reference for the research and development of TME targeted drugs for esophageal carcinoma.

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

Cancer is a major global public health problem. Statistics from the national cancer center of China also show that cancer has become a major disease threatening human health with increasing morbidity and mortality. The occurrence and development mechanism of cancer is complex， involving multiple stages， multiple genes and multiple signaling pathways. Conventional chemoradiotherapy and emerging targeted therapy methods are the main methods in treatment of tumor. However， the quality of life of patients as well as the sustained and effective therapeutic effect are seriously affected due to the toxic side effects and drug resistance. Therefore， it is the global focus to find safe and effective anti-cancer drugs. The research and development and application of anti-cancer herbal medicines such as paclitaxel， vinblastine， podophyllin， ginsenoside and ginseng polysaccharide have brought new hope for the treatment of cancer. Cucurbitacine from Chinese medicine cucurbitaceae plantsare is a kind of highly oxidized tetracyclic triterpene compound with extensive pharmacological effects and complex mechanism. In the family of cucurbitacines， cucurbitin B， D， E and I have been studied most frequently on anticancer effect， and in a large number of studies， they have been found to play an important role in tumor diseases of the digestive system， respiratory system， reproductive system， blood system， urinary system and so on. With significant effect in inhibiting tumor cells proliferation， blocking the cell cycle， inducing apoptosis and autophagy death， inhibiting cell migration and invasion， inhibiting tumor angiogenesis， regulating the levels of reactive oxygen species and regulating immune system， such cucurbitacins are expected to be developed as a new kind of anti-cancer drugs. The authors of this study aim to provide reference for the further research and development of new anti-cancer drugs about cucurbitines by summarizing the anti-tumor effect and mechanism of the cucurbitacins.

Chinese Medicine Injections in Treatment of Esophageal Cancer： A Review / 中国实验方剂学杂志

Esophageal cancer has a high morbidity and mortality worldwide， and the burden of esophageal cancer is still heavy in China. The conventional treatments such as radiotherapy and chemotherapy fail to yield a satisfactory outcome， implying that the safe and effective treatments are not available for the majority of patients. At present， esophageal cancer is mainly treated by Chinese medicine combined with radiotherapy and chemotherapy. The retrieval of related papers in Chinese and English reveals that Kang'ai injection， Compound Kushen injection， Kanglaite injection， Xiaoaiping injection， Aidi injection， Bruceae Fructus Oil Emulsion， Cinobufotalin injection， and Shenmai injection have been commonly used in esophageal cancer treatment. These eight injections are either single medicinal or compound preparations， involving 11 Chinese medicinals， which synergize the effects of radiotherapy and chemotherapy and reduce their adverse reactions in the treatment of esophageal cancer. Due to the complexity of Chinese medicinal components， a series of adverse reactions such as phlebitis， phlebosclerosis， and hemolysis may be caused by irrational dosage， administration speed， and compatibility in the use of injection. There are many clinical studies on Chinese medicine injections for anti-esophageal cancer but few studies on their active components and molecular mechanism. This paper reviewed the active components， effectiveness， safety， and mechanism of Chinese medicine injections frequently employed for treating esophageal cancer， in order to provide reference for their clinical application as well as the development of new Chinese drugs.

Identification and Expression Analysis of TIFY Transcription Factor in Eucommia ulmoides / 中国实验方剂学杂志

Objective:To identify the TIFY gene family in <italic>Eucommia ulmoides</italic> and analyze its expression from the whole genome level to lay the foundation for further study on <italic>EuTIFYs</italic> gene function. Method:Based on the <italic>E. ulmoides</italic> genome database，the TIFY gene family was identified through bioinformatics analysis tools such as National Center for Biotechnology Information（NCBI），MEME，PlantCare，Expert Protein Analysis System（ExPASy），and TBtools. Physicochemical properties，phylogenetic evolution，gene structure，<italic>cis</italic>-acting elements of the promoters and their expression patterns in leaf development and gum formation of the gene family were systematically analyzed. Result:In this study，fourteen <italic>EuTIFY</italic> genes （<italic>EuTIFY1</italic>-<italic>EuTIFY14</italic>） were identified in the <italic>E. ulmoides</italic> genome. The <italic>EuTIFYs</italic> were composed of 312-1 074 bp nucleotides encoding 102-357 amino acid residues，with isoelectric points of 4.99-10.06 and molecular weight in the range of 10.8-39.14 kDa. According to putative subcellular localization，proteins，which were mainly hydrophilic proteins，localized in the nucleus. The 14 <italic>EuTIFYs</italic> were unevenly distributed on 13 chromosomes. <italic>EuTIFY</italic> gene family was divided into four subfamilies： <italic>TIFY</italic>，<italic>JAZ</italic>，<italic>ZML</italic>，and <italic>PPD</italic>，which contained three，four，five，and two members respectively. The promoters of <italic>EuTIFYs</italic> contained multiple photoperiodic and abiotic stress-responsive cis-acting elements，which were involved in plant growth and abiotic stress regulation. Expression pattern analysis showed that <italic>EuTIFYs </italic>exhibited different expression levels in different development stages of <italic>E. ulmoides</italic> leaves and multiple interactions，and most of the genes were highly expressed in the early stage of leaf development and positively regulated the formation of <italic>E. ulmoides</italic> gum. Conclusion:Fourteen <italic>EuTIFYs</italic> were identified from the whole genome of <italic>E. ulmoides</italic>，and their structural characteristics and expression patterns were analyzed by bioinformatics. The findings of this study are expected to provide references for further research on the function of <italic>EuTIFYs</italic>.

Effect of Chinese Medicine Regulating Protein Phosphorylation on Tumorigenesis and Development / 中国实验方剂学杂志

Protein phosphorylation is one of the main ways to activate protein bioactivity and make it participate in cell life activities. Researches have shown that approximately 30% of proteins in the human body are modified by phosphorylation at different levels and at different sites. If the protein phosphorylation modification level or site is abnormal, it will cause the occurrence and development of malignant tumors. Malignant tumors have always been a kind of diseases that endanger human life and health. According to statistics, as many as 18 million malignant tumors and more than 9.6 million deaths occur every year worldwide. With the continuous recognition on the abnormality of protein phosphorylation modification in tumorigenesis and development, the research and development of drugs for abnormality of protein phosphorylation modification has become a focus in the field of tumor therapy at present. Each traditional Chinese medicine(TCM) can be regarded as a natural molecular library, and it participates in the regulation of protein phosphorylation modification level with the advantages of multiple components and multiple targets, with slight side effect and low drug resistance, so TCM is one of the main sources of drug development for regulating protein phosphorylation modification levels. Through the search of multiple databases at home and abroad, it was found that certain monomers, parts extracted from TCM, single-TCM and TCM compounds can affect the tumor progression by regulating the level of protein phosphorylation and exert better anti-tumor effect. Based on the current research status of protein phosphorylation regulation by TCM at home and abroad, we found that TCM can inhibit tumor cell proliferation, invasion and metastasis, angiogenesis, and maintenance of stem cell stemness by regulating protein phosphorylation levels, and exert antitumor effects by promoting apoptosis. In order to clarify the molecular mechanism of TCM in regulating protein phosphorylation level and exerting antitumor effect, and provide evidences for the development and clinical application of antitumor TCM, the authors reviewed the mechanism of TCM in regulating protein phosphorylation level and exerting their antitumor effect from different ways in this paper.