Abstract. Traditional Chinese medicine (TCM) has been a major part of healthcare in China, and has extensively affected medicine and healthcare in surrounding countries over a long period of time. In the fight against cancer, certain anticancer remedies using herbs or herbal formulas derived from TCM have been developed for the management of malignancies. Furthermore, there are clinical trials registered for the use of herbal remedies in cancer management. Herbal medicine has been used as part of combined therapies to reduce the side-effects of chemotherapy, including bone marrow suppression, nausea and vomiting. Herbal remedies have also been used as chemopreventive therapies to treat precancerous conditions in order to reduce the incidence of cancer in high-risk populations. Emerging evidence has revealed that herbal remedies can regulate the proliferation, apoptosis, adhesion and migration of cancer cells. In addition to this direct effect upon cancer cells, a number of herbal remedies have been identified to suppress angiogenesis and therefore reduce tumour growth. The inhibition of tumour growth may also be due to modifications of the host immune system by the herbal treatment. However, the precise mechanisms underlying the therapeutic effects of herbal remedies remain poorly understood and are yet to be fully elucidated. The present study aims to summarize the current literature and clinical trial results of herbal remedies for cancer treatment, with a particular focus on the recent findings and development of the Yangzheng Xiaoji capsule.

Neoadjuvant chemotherapy is a common treatment for patients with gastric cancer. Although its benefits have been demonstrated, neoadjuvant chemotherapy is underutilized in gastric cancer management, because of the lack of biomarkers for patient selection and a limited understanding of resistance mechanisms. Here, we performed whole-genome, whole-exome, and RNA sequencing on 84 clinical samples (including matched pre- and posttreatment tumors) from 35 patients whose responses to neoadjuvant chemotherapy were rigorously defined. We observed increased microsatellite instability and mutation burden in nonresponse tumors. Through comparisons of response versus nonresponse tumors and pre- versus posttreatment samples, we found that C10orf71 mutations were associated with treatment resistance, which was supported by drug response data and potentially through inhibition of cell cycle, and that MYC amplification correlated with treatment sensitivity, whereas MDM2 amplification showed the opposite pattern. Neoadjuvant chemotherapy also reshapes tumor-immune signaling and microenvironment. Our study provides a critical basis for developing precision neoadjuvant regimens.

BackgroundKIAA1199 was upregulated in diverse cancers, but the association of KIAA1199 with gastric cancer (GC), the biological role of KIAA1199 in GC cells and the related molecular mechanisms remain to be elucidated.MethodsKIAA1199 expression was analysed by reverse transcription-polymerase chain reaction assay (RT-PCR) and immunohistochemistry (IHC) in GC patient tissue. The small hairpin RNA (shRNA) was applied for the knockdown of endogenous KIAA1199 in NCI-N87 and AGS cells. MTT, colony formation, scratch wounding migration, transwell chamber migration and invasion assays were employed respectively to investigate the role of KIAA1199 in GC cells. The potential signaling pathway of KIAA1199 induced migration and invasion was detected.ResultsKIAA1199 was upregulated in GC tissue and was an essential independent marker for poor prognosis. Knockdown KIAA1199 suppressed the proliferation, migration and invasion in GC cells. KIAA1199 stimulated the Wnt/β-catenin signaling pathway and the enzymatic activity of matrix metalloproteinase (MMP) family members and thus accelerated the epithelial-to-mesenchymal transition (EMT) progression in GC cells.ConclusionThese findings demonstrated that KIAA1199 was upregulated in GC tissue and associated with worse clinical outcomes in GC, and KIAA1199 acted as an oncogene by promoting migration and invasion through the enhancement of Wnt/β-catenin signaling pathway and MMPs mediated EMT progression in GC cells.

Background:DAP3 is a member of the death-associated protein (DAP) family and is characterised by proapoptotic function. It is involved in both exogenous and endogenous apoptotic pathways. In our previous studies, apoptotic level was found to be correlated with the effectiveness of preoperative chemotherapy. The effectiveness of preoperative chemotherapy was also associated with the overall effectiveness of the combined therapy and prognosis. The present study aimed to investigate the role of DAP3 in the evaluation of preoperative chemotherapy effectiveness and its ability to predict prognosis in gastric cancer.Methods:Quantitative PCR and immunohistochemistry staining were performed in 87 patients who received combined therapy. Knockdown of DAP3 was conducted in gastric cancer cell lines to investigate its impact on cell growth, migration, adhesion and invasion. Tolerance to chemotherapy agents was determined by assessing apoptosis and caspase-3.Results:Higher DAP3 expression in gastric tumours was correlated with better prognosis. Knockdown of DAP3 expression promoted cell migration and enhanced resistance to chemotherapy by inhibiting apoptosis.Conclusion:DAP3 is a potential molecular marker for response to preoperative chemotherapy and for predicting prognosis in gastric cancer patients treated with neoadjuvant chemotherapy and gastrectomy.

Metastasis is a complex multistep process that involves the impairment of cell-cell adhesion in the neoplastic epithelium, invasion into adjacent tissues and the dissemination of cancer cells through the lymphatic and haematogenous routes. The inhibition of the metastatic process at an early stage has become a hot topic in cancer research. The Kiss-1 gene, initially described as a suppressor of metastasis in malignant melanoma, encodes the Kiss-1 protein which can be processed to other peptides, e.g., Kisspeptin-10, Kisspeptin-13, Kisspeptin-14 and Kisspeptin-54. These peptides are endogenous ligands of the Kiss‑1 receptor (Kiss-1R), a G protein-coupled receptor (GPR) also known as hOT7T175, AXOR12 or GPR54. The Kiss-1 gene has been suggested as a suppressor of metastasis in a various types of cancer, including gastric cancer, oesophageal carcinoma, pancreatic, ovarian, bladder and prostate cancer, through the regulation of cellular migration and invasion. In the current review, we summarise the current understanding of the role of Kiss‑1 and Kiss‑1R in cancer and cancer metastasis.

Camellia oleifera Abel., belonging to the genus Camellia of Theaceae, has been widely used as a cooking oil, lubricant, and in cosmetics. Because of complicated polyploidization and large genomes, reference genome information is still lacking. Systematic characterization of gene models based on transcriptome data is a fast and economical approach for C. oleifera. Pacific Biosciences single-molecule long-read isoform sequencing (Iso-Seq) and Illumina RNA-Seq combined with gas chromatography were performed for exploration of oil biosynthesis, accumulation, and comprehensive transcriptome analysis in C. oleifera seeds at five different developmental stages. We report the first full-length transcriptome data set of C. oleifera seeds comprising 40,143 deredundant high-quality isoforms. Among these isoforms, 37,982 were functionally annotated, and 271 (2.43%) belonged to fatty acid metabolism. A total of 8,344 full-length unique transcript models were obtained, and 8,151 (97.69%) of them produced more than two isoforms, suggesting a high degree of transcriptome complexity in C. oleifera seeds. A total of 783 alternative splicing (AS) events were identified, among which the retained intron was the most abundant. We also obtained 1,910 long noncoding RNAs (lncRNAs) and found that AS events occurred in these lncRNAs. Potential transcript variants of genes involved in oil biosynthesis were also investigated. After performing weighted correlation network analysis, we found seven “gene modules” and hub genes for each module showing a significant association with oil content. The series test of clusters classified these modules into four significant profiles based on gene expression patterns. Protein–protein interaction network analysis showed that upregulated WRI1 interacted with 17 genes encoding the enzymes playing key roles in oil synthesis. MYB and ZIP transcriptional factors also showed significant interactions with key genes involved in oil synthesis. Collectively, our data advance the knowledge of RNA isoform diversity in seeds at different developmental stages and provide a rich resource for functional studies on oil synthesis in C. oleifera.

Background:It has recently been shown that WISP proteins (Wnt-inducted secreted proteins), a group of intra- and extra-cellular regulatory proteins, have been implicated in the initiation and progression of a variety of tumour types including colorectal and breast cancer. However, the role of WISP proteins in gastric cancer (GC) cells and their clinical implications have not yet been elucidated.Methods:The expression of WISP molecules in a cohort of GC patients was analysed using real-time quantitative PCR and immunohistochemistry. The expression of a panel of recognised epithelial–mesenchymal transition (EMT) markers was quantified using Q-PCR in paired tumour and normal tissues. WISP-2 knockdown (kd) sublines using ribozyme transgenes were created in the GC cell lines AGS and HGC27. Subsequently, several biological functions, including cell growth, adhesion, migration and invasion, were studied. Potential pathways for the interaction of EMT, extracellular matrix and MMP were evaluated.Results:Overexpression of WISP-2 was detected in GC and significantly correlated with early tumour node-metastasis staging, differentiation status and positively correlated with overall survival and disease-free survival of the patients. WISP-2 expression was inversely correlated with that of Twist and Slug in paired samples. Kd of WISP-2 expression promoted the proliferation, migration and invasion of GC cells. WISP-2 suppressed GC cell metastasis through reversing EMT and suppressing the expression and activity of MMP9 and MMP2 via JNK and ERK. Cell motility analysis indicated that WISP-2 kd contributed to GC cells' motility and can be attenuated by PLC-γ and JNK small inhibitors.Conclusions:Increased expression of WISP-2 in GC is positively correlated with favourable clinical features and the survival of patients with GC and is a negative regulator of growth, migration and invasion in GC cells. These findings suggest that WISP-2 is a potential tumour suppressor in GC.

Background Long non-coding RNA (lncRNA) ASB16 antisense RNA 1 (ASB16-AS1) is recognized as an oncogene in several cancer types, but its relation to GC is unknown. Tripartite motif containing 37 (TRIM37) has been proven to accelerate the development of gastric cancer (GC), whereas the molecular mechanism assisted ASB16-AS1 and TRIM37 in regulating GC progression remains unclear. Methods Differentially expressed lncRNAs in GC samples were analyzed based on Gene Expression Omnibus (GEO) data. CCK-8 and colony formation assays were applied to determine the proliferative ability of GC cells. Stem cell-like phenotype of GC cells was assessed by sphere formation assay and flow cytometry analysis. Luciferase reporter assay, RNA immunoprecipitation (RIP), pulldown, and co-immunoprecipitation (Co-IP) were performed to verify the interplay of RNA molecules. Results ASB16-AS1 was upregulated in GC samples according to GEO data and qRT-PCR analysis. ASB16-AS1 strengthened the proliferative ability and stem cell-like characteristics in GC cells. More importantly, ASB16-AS1 encouraged GC cell growth in vivo. Mechanistically, ASB16-AS1 strengthened TRIM37 expression by sequestering miR-3918 and miR-4676-3p. ASB16-AS1 activated NF-kappa B (NF-κB) pathway by cooperating with ATM serine/threonine kinase (ATM) to induce TRIM37 phosphorylation. Conclusion In summary, ASB16-AS1 exerted oncogenic functions in GC through modulating TRIM37 expression at both mRNA and protein levels.