Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits

Accumulating evidence indicates that the gut microbiome and metabolites are associated with colorectal cancer (CRC). However, the influence of surgery for CRC treatment on the gut microbiome and metabolites and how it relates to CRC risk in postoperative CRC patients remain partially understood. Here, we collected 170 fecal samples from 85 CRC patients pre- and approximately 1 year post-surgery and performed shotgun metagenomic sequencing and capillary electrophoresis-time of flight mass spectrometry-based metabolomics analyses to characterize alterations between pre- and postsurgery. We determined that the relative abundance of 114 species was altered postsurgery (P IMPORTANCE The gut microbiome and metabolites are associated with CRC progression and carcinogenesis. Postoperative CRC patients are reported to be at an increased CRC risk; however, how gut microbiome and metabolites are related to CRC risk in postoperative patients remains only partially understood. In this study, we investigated the influence of surgical CRC treatment on the gut microbiome and metabolites. We found that the CRC-associated species Fusobacterium nucleatum was decreased postsurgery, whereas carcinogenesis-associated DCA and its producing species and genes were increased postsurgery. We developed methods to estimate postoperative CRC risk based on the gut microbiome and metabolomic compositions. We applied methods to compare the estimated CRC risk between two groups according to the presence of large adenoma or tumors after 5 years postsurgery. To our knowledge, this study is the first report on differences between pre- and postsurgery using metagenomics and metabolomics data analysis. Our methods might be used for CRC risk assessment in postoperative patients.</p

Comprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System

The neuroendocrine carcinoma of the gastrointestinal system (GIS-NEC) is a rare but highly malignant neoplasm. We analyzed 115 cases using whole-genome/exome sequencing, transcriptome sequencing, DNA methylation assays, and/or ATAC-seq and found GIS-NECs to be genetically distinct from neuroendocrine tumors (GIS-NET) in the same location. Clear genomic differences were also evident between pancreatic NECs (Panc-NEC) and nonpancreatic GIS-NECs (Nonpanc-NEC). Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic features. Alterations in TP53 and RB1 proved common in GIS-NECs, and most Nonpanc-NECs with intact RB1 demonstrated mutually exclusive amplification of CCNE1 or MYC. Alterations of the Notch gene family were characteristic of Nonpanc-NECs. Transcription factors for neuroendocrine differentiation, especially the SOX2 gene, appeared overexpressed in most GIS-NECs due to hypermethylation of the promoter region. This first comprehensive study of genomic alterations in GIS-NECs uncovered several key biological processes underlying genesis of this very lethal form of cancer. SIGNIFICANCE: GIS-NECs are genetically distinct from GIS-NETs. GIS-NECs arising in different organs show similar histopathologic features and share some genomic features, but considerable differences exist between Panc-NECs and Nonpanc-NECs. In addition, Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic and epigenomic features. This article is highlighted in the In This Issue feature, p. 587

Promotion and Implementation of Audit Bureau of Circulations (ABC) in Taiwan: What Can We Learn from the Japanese Experience

　　發行量，對台灣的平面媒體而言一向是採保密態度，不做對外公開。然而對廣告主而言，將廣告預算投入有效媒體中，才能真正發揮行銷功能。對廣告代理商而言，善用有效媒體，才能替廣告主策劃最有效果的媒體購買計畫。因此，公平、公正、公開的「發行量稽核」，對廣告主、廣告代理商、媒體都是正面而有意義的。 　　本研究針對目前台灣成立ABC組織之推動與執行情況，與日本ABC組織之執行與推動情況作深入了解，並且彙整台灣與日本的實務界與學術界的觀點，探討： 　　1. 台灣ABC執行之爭議點 　　2. 日本ABC執行之經驗 　　3. 台灣ABC未來之發展 　　在研究方法上，先進行文獻探討、資料分析、與深度訪談，並深入分析日本與台灣兩地在推動上之差異性與共通性，以便為上述三點找出答案。 　　本研究中發現，台灣ABC組織目前仍存在之爭議點，在於媒體基於業務考量不願意公佈發行量，以及廣告主對於ABC組織不太重視與對ABC組織的信賴度問題。除非具有公信力，實質運作上客觀公正，有能力提供具體有效的稽核方法讓廣告主、廣告公司信服。因此，若交由廣告主來推動，讓廣告主決定將廣告刊登在有效且經過ABC組織稽核過的媒體上，相信對台灣ABC組織在執行與推動上必然會有所進展。 　　未來在台灣ABC組織或執行上無論廣告主、廣告代理商、媒體等都應該建立共識。廣告主必須透過廣告代理商向媒體施壓積極宣導發行量稽核的概念，為廣告發行的良性發展，ABC的存在與推動是絕對必要的。為達此共識，廣告主應適度施壓給媒體與廣告代理商，並邀請具有規模的報業集團加入稽核，因此廣告主協會(Advertisers Association, AA)應扮演更積極的角色。 日文摘要　　The circulation figures of printed media always have been treated as confidential information by almost all publishers in Taiwan; they are seldom open to the public. However, to an advertiser, satisfactory marketing results can be obtained only through efficiently investing his advertising agency must prepare beforehand thoughtful media plan, or an effective media strategy. 　　This research explores the present Audit Bureau of Circulations (i.e. ABC) in Taiwan and also its counterpart in Japan, in terms of their positions, organizations, and activities; it also searches for the views of practitioners and academic in both Taiwan and Japan, so as to help understand: 　　1. Disputes about ABC activities in Taiwan 　　2. ABC activities in Japan 　　3. Future developments of ABC in Taiwan 　　As regards the research approach, this study first examined all related literature in this field, made data analysis, conducted in-depth interviews, and finally analyzed the differences and similarities of ABC activities in both Taiwan and Japan, in order to find answers to the above-stated three points. 　　Finally, the findings of this research turns out to be that: (1) publishers of Taiwan printed media, considering circulation figures as their business secret, usually are extremely reluctant to disclose such kind of data; (2) Taiwan advertisers neither value nor believe the reliability of ABC activities; and (3) unless ABC in Taiwan provides completely objective circulations report based on reliable auditing, both advertisers and advertising agencies cannot be easily won over. In fact, only when both advertisers and advertising agencies could recognize ABC functions, and also place advertisements in ABC-audited publications, then ABC would be enabled to play a real auditor’s role. 　　In the future, advertisers, advertising agencies, and media in Taiwan must build up a consensus on the organization and activities of ABC. In other words, advertisers should ask advertising agencies to select only audited publications, request leading publishers to support ABC and its auditing, and meanwhile demand all printed media to present their circulation figures to ABC. In other words, the Advertisers Association in Taiwan is obliged to play a more active role in this meaningful endeavor

Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate

<p>Inorganic polyphosphate [poly(P)] is a biopolymer existing in almost all cells and tissues, although its biological functions in higher eukaryotes have not been completely elucidated. We previously demonstrated that poly(P) enhances the function of fibroblast growth factors (FGFs) by stabilizing them and strengthening the affinity between FGFs and their cell surface receptors. Since FGFs play crucial roles in bone regeneration, we further investigated the effect of poly(P) on the cell differentiation of human stem cells via FGF signaling systems. Human dental pulp cells (HDPCs) isolated from human dental pulp show the characteristics of multipotent mesenchymal stem cells (MSCs). HDPCs secreted FGFs and the proliferation of HDPCs was shown to be enhanced by treatment with poly(P). Cell surface receptor-bound FGF-2 was stably maintained for more than 40 hours in the presence of poly(P). The phosphorylation of ERK1/2 was also enhanced by poly(P). The effect of poly(P) on the osteogenic differentiation of HDPCs and human MSCs (hMSCs) were also investigated. After 5 days of treatment with poly(P), type-I collagen expression of both cell types was enhanced. The C-terminal peptide of type-I collagen was also released at higher levels in poly(P)-treated HDPCs. Microarray analysis showed that expression of matrix metalloproteinase-1 (MMP1), osteopontin (OPN), osteocalcin (OC) and osteoprotegerin was induced in both cell types by poly(P). Furthermore, induced expression of MMP1, OPN and OC genes in both cells was confirmed by real-time PCR. Calcification of both cell types was clearly observed by alizarin red staining following treatment with poly(P). The results suggest that the activation of the FGF signaling pathway by poly(P) induces both proliferation and mineralization of stem cells.</p