Dataset Information

Clusterin: Review of research progress and looking ahead to direction in hepatocellular carcinoma.

ABSTRACT: Liver cancer, a large proportion of which is hepatocellular carcinoma (HCC), is diagnosed in more than 700000 people each year worldwide. Liver cancer is particularly prevalent in Asia, Sub-Saharan Africa and the South Pacific, where hepatitis B and hepatitis C infection rates are very high. However, due to resistance to chemotherapy, patients with intermediate and advanced-stage disease cannot benefit from this treatment. Clusterin, which is overexpressed in many different cancers, is a stress-induced cytoprotective protein that confers treatment resistance. Custirsen (OGX-011) is a novel 2'-methoxyethyl modified phosphorothioate antisense oligonucleotide that targets secretory clusterin protein expression and is currently in clinical trials for patients with different cancers. In recent years, a number of different clinical trials have been performed, and two phase III clinical trials of custirsen evaluating combinations with chemotherapy in patients with metastatic castration-resistant prostate cancer and metastatic non-small cell lung cancer are currently in progress. The aims of this review are to summarize the current state of research on clusterin, predict future research directions and analyze the potential of the clinical application of custirsen in HCC.

SUBMITTER: Xiu P

PROVIDER: S-EPMC4507096 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Clusterin: Review of research progress and looking ahead to direction in hepatocellular carcinoma.

Xiu Peng P Dong Xiao-Feng XF Li Xin-Ping XP Li Jie J

World journal of gastroenterology 20150701 27

Liver cancer, a large proportion of which is hepatocellular carcinoma (HCC), is diagnosed in more than 700000 people each year worldwide. Liver cancer is particularly prevalent in Asia, Sub-Saharan Africa and the South Pacific, where hepatitis B and hepatitis C infection rates are very high. However, due to resistance to chemotherapy, patients with intermediate and advanced-stage disease cannot benefit from this treatment. Clusterin, which is overexpressed in many different cancers, is a stress- ...[more]

PMID: 26217078

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Project description:BackgroundThe genus Allium (Family: Amaryllidaceae) is an economically important group of crops cultivated worldwide for their use as a vegetable and spices. Alliums are also well known for their nutraceutical properties. Among alliums, onion, garlic, leek, and chives cultivated worldwide. Despite their substantial economic and medicinal importance, the genome sequence of any of the Allium is not available, probably due to their large genome sizes. Recently evolved omics technologies are highly efficient and robust in elucidating molecular mechanisms of several complex life processes in plants. Omics technologies, such as genomics, transcriptomics, proteomics, metabolomics, metagenomics, etc. have the potential to open new avenues in research and improvement of allium crops where genome sequence information is limited. A significant amount of data has been generated using these technologies for various Allium species; it will help in understanding the key traits in Allium crops such as flowering, bulb development, flavonoid biosynthesis, male sterility and stress tolerance at molecular and metabolite level. This information will ultimately assist us in speeding up the breeding in Allium crops.MethodIn the present review, major omics approaches, and their progress, as well as potential applications in Allium crops, could be discussed in detail.ResultsHere, we have discussed the recent progress made in Allium research using omics technologies such as genomics, transcriptomics, micro RNAs, proteomics, metabolomics, and metagenomics. These omics interventions have been used in alliums for marker discovery, the study of the biotic and abiotic stress response, male sterility, organ development, flavonoid and bulb color, micro RNA discovery, and microbiome associated with Allium crops. Further, we also emphasized the integrated use of these omics platforms for a better understanding of the complex molecular mechanisms to speed up the breeding programs for better cultivars.ConclusionAll the information and literature provided in the present review throws light on the progress and potential of omics platforms in the research of Allium crops. We also mentioned a few research areas in Allium crops that need to be explored using omics technologies to get more insight. Overall, alliums are an under-studied group of plants, and thus, there is tremendous scope and need for research in Allium species.

Project description:Introduction Research on hepatocellular carcinoma (HCC) has grown significantly, and researchers cannot access the vast amount of literature. This study aimed to explore the research progress in studying HCC over the past 30 years using a machine learning-based bibliometric analysis and to suggest future research directions. Methods Comprehensive research was conducted between 1991 and 2020 in the public version of the PubMed database using the MeSH term “hepatocellular carcinoma.” The complete records of the collected results were downloaded in Extensible Markup Language format, and the metadata of each publication, such as the publication year, the type of research, the corresponding author’s country, the title, the abstract, and the MeSH terms, were analyzed. We adopted a latent Dirichlet allocation topic modeling method on the Python platform to analyze the research topics of the scientific publications. Results In the last 30 years, there has been significant and constant growth in the annual publications about HCC (annual percentage growth rate: 7.34%). Overall, 62,856 articles related to HCC from the past 30 years were searched and finally included in this study. Among the diagnosis-related terms, “Liver Cirrhosis” was the most studied. However, in the 2010s, “Biomarkers, Tumor” began to outpace “Liver Cirrhosis.” Regarding the treatment-related MeSH terms, “Hepatectomy” was the most studied; however, recent studies related to “Antineoplastic Agents” showed a tendency to supersede hepatectomy. Regarding basic research, the study of “Cell Lines, Tumors,’’ appeared after 2000 and has been the most studied among these terms. Conclusion This was the first machine learning-based bibliometric study to analyze more than 60,000 publications about HCC over the past 30 years. Despite significant efforts in analyzing the literature on basic research, its connection with the clinical field is still lacking. Therefore, more efforts are needed to convert and apply basic research results to clinical treatment. Additionally, it was found that microRNAs have potential as diagnostic and therapeutic targets for HCC.

Project description:We search for ischemic stroke treatment knowing we have failed-intensely and often-to translate mechanistic knowledge into treatments that alleviate our patients' functional impairments. Lessons can be derived from our shared failures that may point to new directions and new strategies. First, the principle criticisms of both preclinical and clinical assessments are summarized. Next, previous efforts to develop single-mechanism treatments are reviewed. Finally, new definitions, novel approaches, and different directions are presented. In previous development efforts, the basic science and preclinical assessment of candidate treatments often lacked rigor and sufficiency; the clinical trials may have lacked power, rigor, or rectitude; or most likely both preclinical and clinical investigations were flawed. Single-target agents directed against specific molecular mechanisms proved unsuccessful. The term neuroprotection should be replaced as it has become ambiguous: protection of the entire neurovascular unit may be called cerebral cytoprotection or cerebroprotection. Success in developing cerebroprotection-either as an adjunct to recanalization or as stand-alone treatment-will require new definitions that recognize the importance of differential vulnerability in the neurovascular unit. Recent focus on pleiotropic multi-target agents that act via multiple mechanisms of action to interrupt ischemia at multiple steps may be more fruitful. Examples of pleiotropic treatments include therapeutic hypothermia and 3K3A-APC (activated protein C). Alternatively, the single-target drug NA-1 triggers multiple downstream signaling events. Renewed commitment to scientific rigor is essential, and funding agencies and journals may enforce quality principles of rigor in preclinical science. Appropriate animal models should be selected that are suited to the purpose of the investigation. Before clinical trials, preclinical assessment could include subjects that are aged, of both sexes, and harbor comorbid conditions such as diabetes or hypertension. With these new definitions, novel approaches, and renewed attention to rigor, the prospect for successful cerebroprotective therapy should improve.

Dataset Information

Clusterin: Review of research progress and looking ahead to direction in hepatocellular carcinoma.

Publications

Clusterin: Review of research progress and looking ahead to direction in hepatocellular carcinoma.

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