Yin-Cold

Traditional Chinese Medicine (TCM) therapies should be tailored according to the different syndrome types. In order to identify the relationship between the TCM Yin-cold (YC) or Yang-heat (YH) syndrome types and the EGFR gene status, we prospectively studied 310 NSCLC patients. TCM YH or YC was diagnosed by three TCM experts. TCM symptoms and signs were entered into a binary cluster analysis. The relationships between the EGFR gene status, YH or YC syndrome types, and classification by cluster analysis were analyzed using the chi-square test and multivariate logistic regression. In the 299 patients who had their EGFR gene tested, 45.24% YC (76/168) and 25.95% YH (34/131) patients had EGFR mutations (p=0.001). Among the 292 patients entered into the cluster analysis, 132 were classified into group A, with signs and symptoms similar to YC, whereas 160 group B patients were similar to YH. In the 281 patients with EGFR tested, 45.67% group A (58/127) and 28.57% group B patients (44/154) had EGFR mutations (p=0.003). The EGFR status was independently correlated with TCM syndrome type and classification by cluster analysis on multivariate logistic regression. NSCLC patients with YC were more likely to have EGFR gene mutations

Chinese Medicine Was Associated with the Epidermal Growth Factor Receptor Gene Status in Non-Small Cell Lung Cancer Patients: Confirmation of a TCM Concept

Traditional Chinese Medicine (TCM) therapies should be tailored according to the different syndrome types. In order to identify the relationship between the TCM Yin-cold (YC) or Yang-heat (YH) syndrome types and the EGFR gene status, we prospectively studied 310 NSCLC patients. TCM YH or YC was diagnosed by three TCM experts. TCM symptoms and signs were entered into a binary cluster analysis. The relationships between the EGFR gene status, YH or YC syndrome types, and classification by cluster analysis were analyzed using the chi-square test and multivariate logistic regression. In the 299 patients who had their EGFR gene tested, 45.24% YC (76/168) and 25.95% YH (34/131) patients had EGFR mutations ( = 0.001). Among the 292 patients entered into the cluster analysis, 132 were classified into group A, with signs and symptoms similar to YC, whereas 160 group B patients were similar to YH. In the 281 patients with EGFR tested, 45.67% group A (58/127) and 28.57% group B patients (44/154) had EGFR mutations ( = 0.003). The EGFR status was independently correlated with TCM syndrome type and classification by cluster analysis on multivariate logistic regression. NSCLC patients with YC were more likely to have EGFR gene mutations

Therapeutic Potential of Plant Secondary Metabolites in the Treatment of Diseases and Drug Development

The importance of natural products, and especially plant secondary metabolites, for the treatment of diseases and drug development has already been obvious in medicine for several thousand years. Thus, this Special Issue of MDPI Biomedicines collects eight top articles from the field as regular full papers in addition to five reviews. All of the published papers are a vibrant source of information on the therapeutic potential of plant secondary metabolites in the treatment of diseases and drug development

Cancer Immunology

The past decade has seen immunotherapy rise to the forefront of cancer treatment. This Special Issue of Cancers aims to elaborate on the latest developments, cutting-edge technologies, and prospects in cancer immunology and immunotherapy. Seventeen exceptional studies, including original contributions and review articles, written by international scientists and physicians, primarily concerning the fields of tumor biology, cancer immunology, therapeutics, and drug development, comprise the main body of this Special Issue

Phytochemical Omics in Medicinal Plants

Medicinal plants are used to treat diseases and provide health benefits, and their applications are increasing around the world. A huge array of phytochemicals have been identified from medicinal plants, belonging to carotenoids, flavonoids, lignans, and phenolic acids, and so on, with a wide range of biological activities. In order to explore our knowledge of phytochemicals with the assistance of modern molecular tools and high-throughput technologies, this book collects recent innovative original research and review articles on subtopics of mechanistic insights into bioactivities, treatment of diseases, profiling, extraction and identification, and biotechnology

Marine Compounds and Cancer 2020

The very first marine-derived anticancer drug, Cytarabine (aka Ara-C, Cytosar-U®), was approved by the FDA in 1969 for the treatment of leukemia. At the beginning of 2021, the list of approved marine-derived anticancer drugs consists of nine substances, five of which received approval within the last two years, demonstrating the rapid evolution of the field. The current book is a collection of scientific articles related to the exponentially growing field of anticancer marine compounds. These articles cover the whole field, from agents with cancer-preventive activity, to novel and previously characterized compounds with anticancer activity, both in vitro and in vivo, as well as the latest status of compounds under clinical development

Investigating high circulating IGF-1 as a risk factor for development of prostate cancer

Prostate cancer is the commonest cancer in UK men. Prostate cancers upregulate type 1 insulin-like growth factor receptor (IGF-1R), and men with high serum IGF-1 have an increased risk of prostate cancer and of dying from prostate cancer. Subjects with low circulating IGF-1 are strongly protected from cancer; together with preclinical and bioinformatic data this supports a causative association. Unpublished Macaulay lab immunohistochemistry (IHC) data found association of high serum IGF-1 with IGF-1R upregulation in malignant prostatic epithelium, and a trend to association with nuclear IGF- 1R, which has a transcriptional role. IGFs are also reported to be immunosuppressive, and could therefore influence anti-tumour immune responses. The main aim of this project was to investigate changes in the tumour epithelium and tumour microenvironment (TME) through which high IGF-1 promotes prostate cancer risk and progression. Firstly, IHC in 6 prostate biopsies showed a trend to increased IGF-1R and significant increase in internalised IGF-1R, suggesting receptor activation, in malignant vs benign prostate epithelium. Chromogenic in situ hybridisation in 17 prostatectomies showed IGF1R mRNA upregulation in malignant areas indicating transcriptional regulation. In prostate cancer cell lines, I found that short (24 hrs) and long term (8-12 weeks, to mimic lifelong high IGF supply) culture in IGF-1 downregulated IGF-1R. This may result from feedback of pathway activation and is inconsistent with tissue level findings. IGF-1 did cause persistent increase in nuclear IGF-1R, which has been associated with advanced prostate cancer stage. Secondly, I tested effects of IGF-1 on the immune mediators in prostate cancer cell cultures. IGF-1 upregulated immune associated genes CXCL8, CXCL10, CCL5, IFNB1 and ARG2, reported to be upregulated by the NF-κB and cytosolic DNA sensing cGAS-STING pathways. In DU145 prostate cancer cells IGF-1 caused phosphorylation of cGAS-STING pathway proteins IRF3 and TBK1, however the mechanism of this effect is not yet clear. IGF-1 also resulted in the transcriptional upregulation of CD274, encoding PD-L1, in prostate cancer and colorectal cancer cells. Analysis of TCGA data suggested that prostate cancers with high endogenous IGF1 mRNA had higher expression of CD274, consistent with my cell line data, and of S1P, CXCL12, CCL5 and CCL4, which are associated with increased tumour infiltration of CD4+ T regulatory (Tregs) and immunosuppressive M2 macrophages. Finally, association of IGF axis components with the TME was characterised using multiplex immunofluorescence (M-IF) and RNA sequencing (RNA-seq). In prostatectomies of men with known serum IGF-1, M-IF and RNA-seq were conducted on 32 Formalin-Fixed Paraffin-Embedded tissues. Patients with high circulating IGF-1 had increased tumour infiltration of CD4+ T cells, a trend to increased PD-L1 positivity but no association with CD4+ or FOXP3+ Treg positivity. RNA-seq analysis on tumour areas was challenging due to poor quality of extracted RNAs, and no differentially expressed genes were identified in tumours of patients with high circulating IGF-1. However, dividing cases by high vs low endogenous IGF1 indicated deregulation of focal adhesion, leukocyte transendothelial migration and macrophage associated pathways. In high IGF1 tumours, upregulated genes included IGF pathway genes FOXO1, BCL2, ZEB1, IGFBP5 (a marker of IGF axis activation), and chemokine CXCL12 that promotes chemotaxis of lymphocytes including Tregs. Downregulated genes included TAP1, required for antigen transport and presentation, SOX4 and NF-κB regulator TRAF4. In 9 fresh frozen prostate tumour samples, single cell RNA-seq showed infiltration of M2 macrophages and MDSCs, with enrichment of IGF1 in tumour infiltrating fibroblasts and of IGF-2 scavenger IGF2R in myeloid cells and proliferating CD8 and NK cells. In summary, IGF-1 promoted sustained nuclear IGF- 1R translocation and upregulated PD-L1 and cytokine expression in prostate cancer cells, and endogenous IGF1 associated with CXCL12 upregulation and TAP1 downregulation, supporting an immunosuppressive role for IGF-1 in localised prostate tumours. These findings have potential relevance to prostate cancer risk, immunotherapy and risk of lethal disease