Colorectal cancer(CRC) is one of the most common malignancies with high prevalence and low 5-year survival.CRC is a heterogeneous disease with a complex,genetic and biochemical background.It is now generally accepted ...Colorectal cancer(CRC) is one of the most common malignancies with high prevalence and low 5-year survival.CRC is a heterogeneous disease with a complex,genetic and biochemical background.It is now generally accepted that a few important intracellular signaling pathways,including Wnt/β-catenin signaling,Ras signaling,and p53 signaling are frequently dysregulated in CRC.Patients with mutant p53 gene are often resistant to current therapies,conferring poor prognosis.Tumor suppressor p53 protein is a transcription factor inducing cell cycle arrest,senescence,and apoptosis under cellular stress.Emerging evidence from laboratories and clinical trials shows that some small molecule inhibitors exert anti-cancer effect via reactivation and restoration of p53 function.In this review,we summarize the p53 function and characterize its mutations in CRC.The involvement of p53 mutations in pathogenesis of CRC and their clinical impacts will be highlighted.Moreover,we also describe the current achievements of using p53 modulators to reactivate this pathway in CRC,which may have great potential as novel anti-cancer therapy.展开更多
The interactions between herbivores and their host plants play a key role in ecological processes. Understanding the width and nature of these interactions is funda- mental to ecology and conservation. Recent research...The interactions between herbivores and their host plants play a key role in ecological processes. Understanding the width and nature of these interactions is funda- mental to ecology and conservation. Recent research on DNA-based inference of trophic associations suggests that the host range of phytophagous insects in the tropics may be wider than previously thought based on traditional observation. However, the reliability of molecular inference of ecological associations, still strongly dependent on PCR and thus exposed to the risk of contamination with environmental DNA, is under debate. Here, we explored alternative procedures to reduce the chance of amplification of external, nondiet DNA, including surface decontamination and analysis of mid/hind guts, comparing the results with those obtained using the standard protocol. We studied 261 specimens in eight species of Neotropical Chrysomelidae that yielded 316 psbA-trnH intergenic spacer sequences （cpDNA marker of putative diets） from unique and multiple-band PCR results. The taxonomic identity of these sequences was inferred using the automated pipeline BAGpipe, yielding results consistent with 31 plant families. Regardless of the proto- col used, a wide taxonomic spectrum of food was inferred for all chrysomelid species. Canonical Correspondence Analysis using these data revealed significant differences at- tributed mainly to species （expectedly, since they represent different ecologies）, but also to treatment （untreated vs. cleaned/gut samples） and PCR results （single vs. multiple bands）. Molecular identification of diets is not straightforward and, regardless of the species＇ niche breadth, combining approaches that reduce external contamination and studying multiple individuals per species may help increasing confidence in results.展开更多
Drug development is a complex and time-consuming endeavor that traditionally relies on the experience of drug developers and trial-and-error experimentation[1,2].The advent of artificial intelligence(AI)technologies,p...Drug development is a complex and time-consuming endeavor that traditionally relies on the experience of drug developers and trial-and-error experimentation[1,2].The advent of artificial intelligence(AI)technologies,particularly emerging generative AI and large language model,is reshaping this traditional paradigm,offering new avenues for efficiency,precision,and innovation[3].In this special issue,we present an overview of AI applications across the entire drug development workflow.Topics include novel molecule generation,drug–target and drug–drug interaction network prediction,molecular property optimization,pharmaceutical research,and related areas.展开更多
Gastric cancer is in decline in most developed countries;however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. Highthroughput methods are rapidly changing our view and ...Gastric cancer is in decline in most developed countries;however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. Highthroughput methods are rapidly changing our view and understanding of the molecular basis of gastric carcinogenesis. Today, it is widely accepted that the molecular complexity and heterogeneity, both interand intra-tumour, of gastric adenocarcinomas presentsignificant obstacles in elucidating specific biomarkers for early detection of the disease. Although genomewide sequencing and gene expression studies have revealed the intricate nature of the molecular changes that occur in tumour landscapes, the collected data and results are complex and sometimes contradictory.Several aberrant molecules have already been tested in clinical trials, although their diagnostic and prognostic utilities have not been confirmed thus far. The gold standard for the detection of sporadic gastric cancer is still the gastric endoscopy, which is considered invasive. In addition, genome-wide association studies have confirmed that genetic variations are important contributors to increased cancer risk and could participate in the initiation of malignant transformation.This hypothesis could in part explain the late onset of sporadic gastric cancers. The elaborate interplay of polymorphic low penetrance genes and lifestyle and environmental risk factors requires additional research to decipher their relative impacts on tumorigenesis.The purpose of this article is to present details of the molecular heterogeneity of sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss issues relevant to the translation of basic research data to clinically valuable tools. The focus of this work is the identification of relevant molecular changes that could be detected non-invasively.展开更多
基金Supported by National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiativeNMRC Clinician-Scientist IRG Grant CNIG11nov38(Zhou J)Chng WJ is also supported by NMRC Clinician Scientist Investigator award
文摘Colorectal cancer(CRC) is one of the most common malignancies with high prevalence and low 5-year survival.CRC is a heterogeneous disease with a complex,genetic and biochemical background.It is now generally accepted that a few important intracellular signaling pathways,including Wnt/β-catenin signaling,Ras signaling,and p53 signaling are frequently dysregulated in CRC.Patients with mutant p53 gene are often resistant to current therapies,conferring poor prognosis.Tumor suppressor p53 protein is a transcription factor inducing cell cycle arrest,senescence,and apoptosis under cellular stress.Emerging evidence from laboratories and clinical trials shows that some small molecule inhibitors exert anti-cancer effect via reactivation and restoration of p53 function.In this review,we summarize the p53 function and characterize its mutations in CRC.The involvement of p53 mutations in pathogenesis of CRC and their clinical impacts will be highlighted.Moreover,we also describe the current achievements of using p53 modulators to reactivate this pathway in CRC,which may have great potential as novel anti-cancer therapy.
文摘The interactions between herbivores and their host plants play a key role in ecological processes. Understanding the width and nature of these interactions is funda- mental to ecology and conservation. Recent research on DNA-based inference of trophic associations suggests that the host range of phytophagous insects in the tropics may be wider than previously thought based on traditional observation. However, the reliability of molecular inference of ecological associations, still strongly dependent on PCR and thus exposed to the risk of contamination with environmental DNA, is under debate. Here, we explored alternative procedures to reduce the chance of amplification of external, nondiet DNA, including surface decontamination and analysis of mid/hind guts, comparing the results with those obtained using the standard protocol. We studied 261 specimens in eight species of Neotropical Chrysomelidae that yielded 316 psbA-trnH intergenic spacer sequences （cpDNA marker of putative diets） from unique and multiple-band PCR results. The taxonomic identity of these sequences was inferred using the automated pipeline BAGpipe, yielding results consistent with 31 plant families. Regardless of the proto- col used, a wide taxonomic spectrum of food was inferred for all chrysomelid species. Canonical Correspondence Analysis using these data revealed significant differences at- tributed mainly to species （expectedly, since they represent different ecologies）, but also to treatment （untreated vs. cleaned/gut samples） and PCR results （single vs. multiple bands）. Molecular identification of diets is not straightforward and, regardless of the species＇ niche breadth, combining approaches that reduce external contamination and studying multiple individuals per species may help increasing confidence in results.
文摘Drug development is a complex and time-consuming endeavor that traditionally relies on the experience of drug developers and trial-and-error experimentation[1,2].The advent of artificial intelligence(AI)technologies,particularly emerging generative AI and large language model,is reshaping this traditional paradigm,offering new avenues for efficiency,precision,and innovation[3].In this special issue,we present an overview of AI applications across the entire drug development workflow.Topics include novel molecule generation,drug–target and drug–drug interaction network prediction,molecular property optimization,pharmaceutical research,and related areas.
文摘Gastric cancer is in decline in most developed countries;however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. Highthroughput methods are rapidly changing our view and understanding of the molecular basis of gastric carcinogenesis. Today, it is widely accepted that the molecular complexity and heterogeneity, both interand intra-tumour, of gastric adenocarcinomas presentsignificant obstacles in elucidating specific biomarkers for early detection of the disease. Although genomewide sequencing and gene expression studies have revealed the intricate nature of the molecular changes that occur in tumour landscapes, the collected data and results are complex and sometimes contradictory.Several aberrant molecules have already been tested in clinical trials, although their diagnostic and prognostic utilities have not been confirmed thus far. The gold standard for the detection of sporadic gastric cancer is still the gastric endoscopy, which is considered invasive. In addition, genome-wide association studies have confirmed that genetic variations are important contributors to increased cancer risk and could participate in the initiation of malignant transformation.This hypothesis could in part explain the late onset of sporadic gastric cancers. The elaborate interplay of polymorphic low penetrance genes and lifestyle and environmental risk factors requires additional research to decipher their relative impacts on tumorigenesis.The purpose of this article is to present details of the molecular heterogeneity of sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss issues relevant to the translation of basic research data to clinically valuable tools. The focus of this work is the identification of relevant molecular changes that could be detected non-invasively.
