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Carlo M. Croce

Bio: Carlo M. Croce is an academic researcher from Ohio State University. The author has contributed to research in topics: microRNA & Cancer. The author has an hindex of 198, co-authored 1135 publications receiving 189007 citations. Previous affiliations of Carlo M. Croce include University of Nebraska Medical Center & University of California, Los Angeles.


Papers
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Journal ArticleDOI
TL;DR: An innovative approach based on the development of artificial microRNAs able to efficiently target mutated KRAS, leaving their normal counterpart unaffected and preventing major side effects.
Abstract: Mutated protein-coding genes drive the molecular pathogenesis of many diseases, including cancer. Specifically, mutated KRAS is a documented driver for malignant transformation, occurring early during the pathogenesis of cancers such as lung and pancreatic adenocarcinomas. Therapeutically, the indiscriminate targeting of wild-type and point-mutated transcripts represents an important limitation. Here, we leveraged on the design of miRNA-like artificial molecules (amiRNAs) to specifically target point-mutated genes, such as KRAS, without affecting their wild-type counterparts. Compared with an siRNA-like approach, the requirement of perfect complementarity of the microRNA seed region to a given target sequence in the microRNA/target model has proven to be a more efficient strategy, accomplishing the selective targeting of point-mutated KRAS in vitro and in vivo.

38 citations

Journal ArticleDOI
01 Dec 1997-Genomics
TL;DR: Analysis of human breast, lung, and ovarian carcinomas revealed the presence of several amino acid substitutions in the coding region of the LOH11CR2A gene, but a role for these amino acid changes in the tumorigenic process could not established.

38 citations

Journal ArticleDOI
TL;DR: Chromosome studies are helping to identify oncogenes, both known and previously unknown, involved in the pathogenesis of human lymphocytic tumors; and mechanisms by which the function of these genes is critically altered.
Abstract: Chromosome studies are helping to identify oncogenes, both known and previously unknown, involved in the pathogenesis of human lymphocytic tumors; and mechanisms by which the function of these genes is critically altered. Most extensively studied have been the chromosome translocations involving the myc gene in Burkitt's lymphomas and the bcl -2 gene in low-grade lymphomas, where “activation” of the oncogene results from association with a transcriptionally active immunoglobulin gene. Other putative oncogenes, similarly involved in translocations with immunoglobulin genes (in B-cell tumors) or T-cell receptor genes (in T-cell tumors), are currently being investigated, as well as alternative mechanisms of myc gene activation in these neoplasms. Limited clinical applications of these studies have already been forthcoming, and they should eventually lead to improvements in diagnosis, prognosis, and even therapy.

38 citations

Journal ArticleDOI
TL;DR: The data indicate that WWOX disruption alters HDL and lipoprotein metabolism through several mechanisms and may account for the low-HDL phenotype observed in families expressing the WWOX variants.
Abstract: Background— Low levels of high-density lipoprotein (HDL) cholesterol constitutes a major risk factor for atherosclerosis. Recent studies from our group reported a genetic association between the WW domain-containing oxidoreductase ( WWOX ) gene and HDL cholesterol levels. Here, through next-generation resequencing, in vivo functional studies and gene microarray analyses, we investigated the role of WWOX in HDL and lipid metabolism. Methods and Results— Using next-generation resequencing of the WWOX region, we first identified 8 variants significantly associated and perfectly segregating with the low-HDL trait in 2 multigenerational French Canadian dyslipidemic families. To understand in vivo functions of WWOX, we used liver-specific Wwox hep−/− and total Wwox −/− mice models, where we found decreased ApoA-I and Abca1 levels in hepatic tissues. Analyses of lipoprotein profiles in Wwox −/−, but not Wwox hep−/− littermates, also showed marked reductions in serum HDL cholesterol concentrations, concordant with the low-HDL findings observed in families. We next obtained evidence of a sex-specific effect in female Wwox hep−/− mice, where microarray analyses revealed an increase in plasma triglycerides and altered lipid metabolic pathways. We further identified a significant reduction in ApoA-I and Lpl and an upregulation in Fas , Angptl4 , and Lipg , suggesting that the effects of Wwox involve multiple pathways, including cholesterol homeostasis, ApoA-I/ABCA1 pathway, and fatty acid biosynthesis/triglyceride metabolism. Conclusions— Our data indicate that WWOX disruption alters HDL and lipoprotein metabolism through several mechanisms and may account for the low-HDL phenotype observed in families expressing the WWOX variants. These findings thus describe a novel gene involved in cellular lipid homeostasis, which effects may impact atherosclerotic disease development.

38 citations

Journal ArticleDOI
TL;DR: There are several high-throughput approaches to quantifying miRNAs in tissue samples, but the gold standard is still unclear and cDNA oligonucleotide arrays have become a standard global-scale technique for miRNA profiling.
Abstract: Studies have demonstrated that miRNAs may be specific to or enriched for tissue and disease types. For example, miR-122 is liver specific while miR-126 in enriched in the vasculature [5,6]. There are several high-throughput approaches to quantifying miRNAs in tissue samples, but the gold standard is still unclear. Northern blotting was initially one of the primary methods used to detect individual small RNAs. cDNA oligonucleotide arrays have become a standard global-scale technique for miRNA profiling [7]. Real-time PCR has been successfully used for detecting low copy number precursor and mature miRNA with high sensitivity and specificity [8]. Deep sequencing is also being used to identify both miRNAs and other noncoding RNAs [9].

38 citations


Cited by
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Journal ArticleDOI
TL;DR: A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original.
Abstract: The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSIBLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.

70,111 citations

Journal ArticleDOI
04 Mar 2011-Cell
TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.

51,099 citations

Journal ArticleDOI
23 Jan 2004-Cell
TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.

32,946 citations

Journal ArticleDOI
TL;DR: This protocol provides an overview of the comparative CT method for quantitative gene expression studies and various examples to present quantitative gene Expression data using this method.
Abstract: Two different methods of presenting quantitative gene expression exist: absolute and relative quantification. Absolute quantification calculates the copy number of the gene usually by relating the PCR signal to a standard curve. Relative gene expression presents the data of the gene of interest relative to some calibrator or internal control gene. A widely used method to present relative gene expression is the comparative C(T) method also referred to as the 2 (-DeltaDeltaC(T)) method. This protocol provides an overview of the comparative C(T) method for quantitative gene expression studies. Also presented here are various examples to present quantitative gene expression data using this method.

20,580 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations