Precision medicine最新文献

Abstract C57: Organoid profiling identifies common responders to chemotherapy in pancreatic cancer 摘要:类器官谱分析可识别胰腺癌化疗的共同应答者

Precision medicine Pub Date : 2019-12-15 DOI: 10.1158/1538-7445.PANCA19-C57

H. Tiriac, P. Belleau, Dannielle D. Engle, Dennis Plenker, Astrid Deschênes, T. Somerville, F. Froeling, R. Moffitt, J. Knox, A. Krasnitz, S. Gallinger, D. Tuveson

{"title":"Abstract C57: Organoid profiling identifies common responders to chemotherapy in pancreatic cancer","authors":"H. Tiriac, P. Belleau, Dannielle D. Engle, Dennis Plenker, Astrid Deschênes, T. Somerville, F. Froeling, R. Moffitt, J. Knox, A. Krasnitz, S. Gallinger, D. Tuveson","doi":"10.1158/1538-7445.PANCA19-C57","DOIUrl":"https://doi.org/10.1158/1538-7445.PANCA19-C57","url":null,"abstract":"Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we find that PDO therapeutic profiles paralleled patient outcomes and that PDOs enable longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection. Citation Format: Herve Tiriac, Pascal Belleau, Dannielle Engle, Dennis Plenker, Astrid Deschenes, Tim Somerville, Fieke Froeling, Richard Moffitt, Jennifer Knox, Alexander Krasnitz, Steven Gallinger, David Tuveson. Organoid profiling identifies common responders to chemotherapy in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C57.","PeriodicalId":90947,"journal":{"name":"Precision medicine","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85072289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

GLOBAL OPIOID EPIDEMIC: DOOMED TO FAIL WITHOUT GENETICALLY BASED PRECISION ADDICTION MEDICINE (PAM^™): LESSONS LEARNED FROM AMERICA. 全球阿片类药物流行病:没有基于基因的精确成瘾药物(pam™)注定要失败:从美国吸取的教训。

Precision medicine Pub Date : 2017-01-01 Epub Date: 2017-11-18

Kenneth Blum, Edward J Modestino, Marjorie C Gondré-Lewis, Jennifer Neary, David Siwicki, Mary Hauser, Debmalya Barh, Bruce Steinberg, Rajendra D Badgaiyan

{"title":"GLOBAL OPIOID EPIDEMIC: DOOMED TO FAIL WITHOUT GENETICALLY BASED PRECISION ADDICTION MEDICINE (PAM™): LESSONS LEARNED FROM AMERICA.","authors":"Kenneth Blum, Edward J Modestino, Marjorie C Gondré-Lewis, Jennifer Neary, David Siwicki, Mary Hauser, Debmalya Barh, Bruce Steinberg, Rajendra D Badgaiyan","doi":"","DOIUrl":"","url":null,"abstract":"It is a reality that globally opioid deaths have soared for men and women of all social, economic status and age from heroin and fentanyl overdoses. Specifically, in the United States, deaths from narcotic overdoses have reached alarming metrics since 2010. In fact, the Fentanyl rise is driven by drug dealers who sell it as heroin or who use it to lace cocaine or to make illegal counterfeit prescription opioids. The President's Commission on the crisis has linked the death toll as equivalent to \"September 11th every three weeks.\" In fact, The U.S. Centre for Disease Control (CDC) released data showing that opioid-related overdoses were up 15% in the first three quarters of 2016 compared to 2015. Various governmental organizations including NIDA, are actively seeking solutions. However, we argue that unless the scientific community embraces genetic addiction risk coupled with potential precision or personalized medicine to induce \"dopamine homeostasis\" it will fail. We now have evidence that a ten-gene and eleven single nucleotide polymorphism (SNP) panel predicts Addiction Severity Index (ASI) for both alcohol and drugs of abuse (e.g., Opioids). In a large multi-addiction centre study involving seven diverse treatment programs, the genetic addiction risk score (GARS™) was shown to have a predictive relationship with ASI-MV derived alcohol (≥ seven alleles), and other drugs (≥ 4 alleles) severity risk scores. In a number of neuroimaging studies, we also display that in both animal (bench) and abstinent Chinese severe heroin-dependent patients (bedside), BOLD dopamine activation across the brain reward circuitry revealed increases in resting state functional connectivity as well volume connectivity. It is also known that published nutrigenomic (coupling gene polymorphisms with altered KB220z) studies reveal improved clinical outcomes related to obesity.","PeriodicalId":90947,"journal":{"name":"Precision medicine","volume":"2 1","pages":"17-22"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778881/pdf/nihms935265.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35768301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functional pseudogenes inhibit the superoxide production. 功能性假基因抑制超氧化物的产生。

Precision medicine Pub Date : 2015-05-06 DOI: 10.14800/PM.745

W. Xu, Li Ma, Wenzhi Li, Tiffany Brunson, Xiaohua Tian, Jendai C. Richards, Qiling Li, Tameka Bythwood, Zuyi Yuan, Qing Song

{"title":"Functional pseudogenes inhibit the superoxide production.","authors":"W. Xu, Li Ma, Wenzhi Li, Tiffany Brunson, Xiaohua Tian, Jendai C. Richards, Qiling Li, Tameka Bythwood, Zuyi Yuan, Qing Song","doi":"10.14800/PM.745","DOIUrl":"https://doi.org/10.14800/PM.745","url":null,"abstract":"We recently discovered a dynamic copy number variation on the NCF1 (neutrophil cytosolic factor 1) pseudogenes in human populations. In this study, we investigated whether these pseudogenes are functional or junk as described before. We sequenced the RNAs transcribed from the genome of this locus, and discovered over 10 splicing isoforms from the NCF1 pseudogenes. We cloned 4 splicing isoforms into expression vectors and introduced them into human vascular endothelial cells by transient transfection. We then used two chemical approaches to measure the superoxide production in the cells with and without these pseudogene overexpression. Our data showed that three pseudogene splicing products remarkably reduced the superoxide production after the GFP (Green fluorescent protein) normalization. We used an anti-HA (Hemagglutinin A) tag antibody to stain the cells and confirmed that the proteins transcribed from the NCF1 pseudogene were exclusively localized in the cytoplasm in the perinuclear area in the transient transfection assays. We further examined the tissue distribution of these splicing isoforms of NCF1 pseudogenes in human tissues by quantitative real-time PCR analysis. Our data showed that although these splicing variants are ubiquitously expressed in non-immune tissues in human, they seem to be under a tight control of transcription regulation and show a non-random distribution pattern across tissues. This study challenges the concept that pseudogenes in human genome are only junks without biological functions. Moreover, it suggests that those pseudogenes in human genome may serve as a natural resource for novel drug discovery.","PeriodicalId":90947,"journal":{"name":"Precision medicine","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87060368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

The mirror RNA expression pattern in human tissues. 镜像 RNA 在人体组织中的表达模式。

Precision medicine Pub Date : 2015-01-01 Epub Date: 2015-10-01 DOI: 10.14800/pm.1036

Tameka N Bythwood, Wei Xu, Wenzhi Li, Weinian Rao, Qiling Li, Xue Xue, Jendai Richards, Li Ma, Qing Song

{"title":"The mirror RNA expression pattern in human tissues.","authors":"Tameka N Bythwood, Wei Xu, Wenzhi Li, Weinian Rao, Qiling Li, Xue Xue, Jendai Richards, Li Ma, Qing Song","doi":"10.14800/pm.1036","DOIUrl":"10.14800/pm.1036","url":null,"abstract":"It has been realized in recent years that non-coding RNAs are playing important roles in genome functions and human diseases. Here we developed a new technology and observed a new pattern of gene expression. We observed that over 72% of RNAs in human genome are expressed in forward-reverse pairs, just like mirror images of each other between forward expression and reverse expression; the overview showed that it cannot be simply described as transcript overlapping, so we designated it as mirror expression. Furthermore, we found that the mirror expression is gene-specific and tissue-specific, and less common in the proximal promoter regions. The size of the shadows varies between different genes, different tissues and different classes. The shadow expression is most significant in the Alu element, it was also observed among L1, Simple Repeats and LTR elements, but rare in other repeats such as low-complexity, LINE/L2, DNA and MIRs. Although there is no evidence yet about the relationship of this mirror pattern and double-strand RNA (dsRNA), this new striking pattern provides a new clue and a new direction to unveil the role of RNAs in the genome functions and diseases.","PeriodicalId":90947,"journal":{"name":"Precision medicine","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340261/pdf/nihms851855.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34800829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functional pseudogenes inhibit the superoxide production. 功能性假基因可抑制超氧化物的产生。

Precision medicine Pub Date : 2015-01-01

Wei Xu, Li Ma, Wenzhi Li, Tiffany A Brunson, Xiaohua Tian, Jendai Richards, Qiling Li, Tameka Bythwood, Zuyi Yuan, Qing Song

{"title":"Functional pseudogenes inhibit the superoxide production.","authors":"Wei Xu, Li Ma, Wenzhi Li, Tiffany A Brunson, Xiaohua Tian, Jendai Richards, Qiling Li, Tameka Bythwood, Zuyi Yuan, Qing Song","doi":"","DOIUrl":"","url":null,"abstract":"We recently discovered a dynamic copy number variation on the NCF1 (neutrophil cytosolic factor 1) pseudogenes in human populations. In this study, we investigated whether these pseudogenes are functional or junk as described before. We sequenced the RNAs transcribed from the genome of this locus, and discovered over 10 splicing isoforms from the NCF1 pseudogenes. We cloned 4 splicing isoforms into expression vectors and introduced them into human vascular endothelial cells by transient transfection. We then used two chemical approaches to measure the superoxide production in the cells with and without these pseudogene overexpression. Our data showed that three pseudogene splicing products remarkably reduced the superoxide production after the GFP (Green fluorescent protein) normalization. We used an anti-HA (Hemagglutinin A) tag antibody to stain the cells and confirmed that the proteins transcribed from the NCF1 pseudogene were exclusively localized in the cytoplasm in the perinuclear area in the transient transfection assays. We further examined the tissue distribution of these splicing isoforms of NCF1 pseudogenes in human tissues by quantitative real-time PCR analysis. Our data showed that although these splicing variants are ubiquitously expressed in non-immune tissues in human, they seem to be under a tight control of transcription regulation and show a non-random distribution pattern across tissues. This study challenges the concept that pseudogenes in human genome are only junks without biological functions. Moreover, it suggests that those pseudogenes in human genome may serve as a natural resource for novel drug discovery.","PeriodicalId":90947,"journal":{"name":"Precision medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467915/pdf/nihms-689541.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33399250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0