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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: The effects of restored Fhit protein expression on cell proliferation, cell kinetics, and tumorigenicity in BALB/c nude mice and the possibility of a FHIT-based gene therapy for bladder cancer are studied.
Abstract: The fragile histidine triad (FHIT) gene located on chromosome 3p14.2 is frequently deleted in human tumors. We have previously reported deletions at the FHIT locus in 50% of bladder carcinoma derived cell lines and reduced expression in 61% of primary transitional carcinomas of the urinary bladder. To additionally investigate the role of FHIT alterations in the development of bladder cancer, we used heterozygous and nullizygous Fhit-deficient mice in a chemically induced carcinogenesis model. Results showed that 8 of 28 (28%) and 6 of 13 (46%) of the Fhit -/- and +/-, respectively, versus 2 of 25 (8%) Fhit +/+ mice developed invasive carcinoma after treatment with N-butyl-N-(4-hydroxybutyl) nitrosamine. To explore the possibility of a FHIT-based gene therapy for bladder cancer, we studied the effects of restored Fhit protein expression on cell proliferation, cell kinetics, and tumorigenicity in BALB/c nude mice, with human SW780 Fhit-null transitional carcinoma derived cells. In vitro transduction of SW780 Fhit-negative cells with adenoviral-FHIT inhibited cell growth, increased apoptotic cell population, and suppressed s.c. tumor growth in nude mice. These findings suggest the important role of Fhit in bladder cancer development and support the effort to additionally investigate a FHIT-based gene therapy.

28 citations

Journal ArticleDOI
TL;DR: The results reported here show that the homozygous genotype for Asp872 of PTPRJ is associated with an increased risk to develop PTC.
Abstract: The strong genetic predisposition to papillary thyroid carcinoma (PTC) might be due to a combination of low-penetrance susceptibility variants. Thus, the research into gene variants involved in the increase of susceptibility to PTC is a relevant field of investigation. The gene coding for the receptor-type tyrosine phosphatasePTPRJ has been proposed as a cancer susceptibility gene, and its role as a tumor suppressor gene is well established in thyroid carcinogenesis. In this study, we want to ascertain the role of PTPRJ genotype in the risk for PTC. We performed a case-control study in which we determined the PTPRJ genotype for the non-synonymous Gln276Pro and Asp872Glu polymorphisms by PCR amplification and sequencing. We calculated allele and genotype frequencies for the considered polymorphisms of PTPRJ in a total sample of 299 cases (PTC patients) and 339 controls (healthy subjects) selected from Caucasian populations. We observed a significantly higher frequency of homozygotes for the Asp872 allele in the group of PTC patients than in the control group (odds ratioZ1.61, 95% confidence interval 1.15-2.25, PZ0.0053). We observed a non-significant increased frequency of homozygotes for Gln276Pro polymorphism in PTC cases in two distinct Caucasian populations. Therefore, the results reported here show that the homozygous genotype for Asp872 of PTPRJ is associated with an increased risk to develop PTC. Endocrine-Related Cancer (2010) 17 1001-1006

28 citations

Journal ArticleDOI
TL;DR: It is discovered that ROR1 an embryonal antigen expressed on most (∼ 90%) CLL, but not on normal B cell, is also regulated by miR-15/16, and CLL cells are also sensitive to monoclonal antibodies against R OR1.
Abstract: By using chronic lymphocytic leukemia as target for discovery in cancer pathogenesis we discovered that the great majority of CLLs (75–85%) carry a deletion of miR-15a and miR-16-1 at 13q14. We also discovered that miR-15/16 are negative regulators of the BCL2 oncogene. Thus the loss of the two negative regulators causes BCL2 overexpression and leukemia. A corollary of this is that CLL is very sensitive to the anti BCL2 drug venetoclax that can induce complete remission in CLL patients. Since leukemia patients may carry billions of leukemia cells, it is quite likely that some (few) of the leukemic cells are resistant to venetoclax. Thus, since microRNAs have multiple targets, we looked for other proteins that may be overexpressed in CLL because of the low of miR-15/16. We discovered that ROR1 an embryonal antigen expressed on most (∼ 90%) CLL, but not on normal B cell, is also regulated by miR-15/16. Thus CLL cells are also sensitive to monoclonal antibodies against ROR1. Venetoclax and monoclonal antibodies against ROR1 act synergistically in killing CLL cells.

28 citations

Journal ArticleDOI
TL;DR: The data suggest that the STAT3 locus is associated with both IBD and cancer, and understanding the function of this variant in relation to TP53 could possibly explain the role of this gene in autoimmunity and cancer.

28 citations

Journal ArticleDOI
TL;DR: Data indicate that miR-181b exerts a broad range of actions, affecting proliferative, survival and apoptotic pathways, both in mice and human cells, and can potentially be used to reduce expansion of B-CLL leukemic cells.
Abstract: // Antonella Bresin 1 , Elisa Callegari 1 , Lucilla D’Abundo 1 , Caterina Cattani 2 , Cristian Bassi 1 , Barbara Zagatti 1 , M. Grazia Narducci 2 , Elisabetta Caprini 2 , Yuri Pekarsky 3 , Carlo M. Croce 3 , Silvia Sabbioni 4 , Giandomenico Russo 2 and Massimo Negrini 1 1 Universita di Ferrara, Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale, Ferrara, Italy 2 Istituto Dermopatico dell’Immacolata, IDI-IRCCS, Laboratorio di Oncologia Molecolare, Rome, Italy 3 Human Cancer Genetics Program and Department of Molecular Virology, Immunology and Medical Genetics, OSU School of Medicine, Ohio State University, Columbus, OH, USA 4 Universita di Ferrara, Dipartimento di Scienze della Vita e Biotecnologie, Ferrara, Italy Correspondence to: Massimo Negrini, email: // Giandomenico Russo, email: // Keywords : chronic lymphocytic leukemia, miR-181b, TCL1, mouse model, gene therapy Received : January 31, 2015 Accepted : May 29, 2015 Published : June 10, 2015 Abstract The involvement of microRNAs (miRNAs) in chronic lymphocytic leukemia (CLL) pathogenesis suggests the possibility of anti-CLL therapeutic approaches based on miRNAs. Here, we used the Eµ-TCL1 transgenic mouse model, which reproduces leukemia with a similar course and distinct immunophenotype as human B-CLL, to test miR-181b as a therapeutic agent. In vitro enforced expression of miR-181b mimics induced significant apoptotic effects in human B-cell lines (RAJI, EHEB), as well as in mouse Eµ-TCL1 leukemic splenocytes. Molecular analyses revealed that miR-181b not only affected the expression of TCL1, Bcl2 and Mcl1 anti-apoptotic proteins, but also reduced the levels of Akt and phospho-Erk1/2. Notably, a siRNA anti-TCL1 could similarly down-modulate TCL1, but exhibited a reduced or absent activity in other relevant proteins, as well as a reduced effect on cell apoptosis and viability. In vivo studies demonstrated the capability of miR-181b to reduce leukemic cell expansion and to increase survival of treated mice. These data indicate that miR-181b exerts a broad range of actions, affecting proliferative, survival and apoptotic pathways, both in mice and human cells, and can potentially be used to reduce expansion of B-CLL leukemic cells.

27 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