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  • Gene Transfer
  • Frank L Graham

    Prominent publications by Frank L Graham

    KOL Index score: 21194

    Cell cycle regulatory proteins are important candidates for therapeutic tumour suppressors. Adenovirus vectors were constructed to overexpress cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21WAF1/CIP1 and p27KIP1 under the control of the murine cytomegalovirus immediate early gene promoter. These vectors directed the efficient expression of each of the cyclin kinase inhibitors and induced growth arrest, inhibited DNA synthesis, and prevented phosphorylation of the ...

    Also Ranks for: Adenovirus Vectors |  kinase inhibitor |  cell cycle |  cyclin dependent |  growth arrest
    KOL Index score: 19923

    Transgenic mice expressing the polyomavirus (PyV) middle T antigen (MT) develop multifocal mammary tumors which frequently metastasize to the lung. The potent transforming activity of PyV MT is correlated with its capacity to activate and associate with a number of signaling molecules, including the Src family tyrosine kinases, the 85-kDa Src homology 2 subunit of the phosphatidylinositol 3' (PI-3') kinase, and the Shc adapter protein. To uncover the role of these signaling proteins in ...

    Also Ranks for: Kinase Signaling |  mammary tumorigenesis |  transgenic mice |  phosphatidylinositol 3 |  polyomavirus middle
    KOL Index score: 14785

    Inflammatory bowel disease (IBD) is characterized by altered immunoregulation and augmented intestinal synthesis of nitric oxide. The purpose of this study was to determine the effects of exogenous IL-4, introduced by a recombinant human type 5 adenovirus (Ad5) vector, on the tissue injury associated with an experimental model of colonic immune activation and inflammation. Colitis was induced in rats by the intrarectal administration of trinitrobenzene sulfonic acid (TNB) dissolved in ...

    Also Ranks for: Gene Transfer |  inflammatory bowel |  ad5il4 ad5lacz |  nitric oxide |  distal colon
    KOL Index score: 14162

    The cloning capacity of currently available E1- and E3-deleted adenovirus (Ad) vectors does not exceed 8 kb. To increase capacity and improve vector safety further, we have explored the possibility that Early Region 4 (E4) and the gene encoding protein IX (pIX) might also be deleted. To generate cell lines expressing sufficient levels of E4 and pIX proteins in trans in addition to E1-encoded proteins to complement mutations in these genes, we transformed 293 cells with constructs ...

    Also Ranks for: Cell Lines |  e4 proteins |  defective adenovirus |  viral dna |  vectors e1
    KOL Index score: 13786

    Tumor necrosis factor-alpha is up-regulated in a variety of different human immune-inflammatory and fibrotic pulmonary pathologies. However, its precise role in these pathologies and, in particular, the mechanism(s) by which it may induce fibrogenesis are not yet elucidated. Using a replication-deficient adenovirus to transfer the cDNA of tumor necrosis factor-alpha to rat lung, we have been able to study the effect of transient but prolonged (7 to 10 days) overexpression of tumor ...

    Also Ranks for: Growth Factor |  tumor necrosis |  rat lung |  gene transfer |  precise role
    KOL Index score: 12518

    We have developed a number of replication defective adenoviral (Ad) vectors which express transgenes under the control of the human cytomegalovirus (HCMV) immediate early (IE) gene promoter. The orientation of the expression cassette replacing E1 in the vector backbone had a significant effect on the level of transgene expression, with vectors containing expression cassettes directed towards the right end of the Ad genome expressing 7-fold higher levels of beta-galactosidase (beta-gal) ...

    Also Ranks for: Transgene Expression |  adenoviral vectors |  hcmv promoter |  murine cytomegalovirus |  early gene
    KOL Index score: 11672

    Adenoviruses are attractive vectors for the delivery of foreign genes into mammalian cells for gene therapy. However, current vectors retain many viral genes that, when expressed at low levels, contribute to the induction of a host immune response against transduced cells. We have developed a helper-dependent packaging system for production of vectors that have large regions of the genome deleted. Helper viruses were constructed with packaging signals flanked by loxP sites so that in 293 ...

    Also Ranks for: Helper Virus |  packaging signal |  vector genome |  viral genes |  dna replication
    KOL Index score: 11661

    The adenovirus 5 early region 1A (ElA: 0–4.5 map units) proteins synthesized early after infection of KB cells without pretreatment of the cells with metabolic inhibitors have been studied. The E1A mRNA species of 1.1 and 0.9 kilobases (Kb) are processed from alternative 5′ splice sites to a common 3′ splice site of the same initial transcript and code for proteins of 289 and 243 amino acids in length that share common amino and carboxy terminal peptides but differ in that 46 residues of ...

    Also Ranks for: E1a Proteins |  human adenovirus type |  early region 1a |  messenger rna |  carboxy terminus
    KOL Index score: 11551

    The infection of epithelia] swine testicle and intestinal porcine epithelial (IPEC-1) cell lines by adenovirus type 5 (Ad5) has been studied in vitro by using an Ad5-luciferase recombinant containing the firefly luciferase gene as a reporter. Porcine cell lines supported Ad5 replication, showing virus titers, kinetics of virus production, and luciferase expression levels similar to those obtained in human 293 cells, which constitutively express the 5'-end 11% of the Ad5 genome. The ...

    Also Ranks for: Transmissible Gastroenteritis |  adenovirus type |  ad5 vectors |  epithelial cells |  viral vaccines
    KOL Index score: 11546

    We have studied the ability of adenoviral (Ad) vectors expressing the cytokines IL-2 or IL-12 to mediate regression of established tumors in a mouse model of mammary adenocarcinoma. Previous results indicated that intratumoral injection of vectors expressing IL-2 (AdCAIL-2) or IL-12 (AdmIL-12.1) induced complete tumor regression in approximately 30–40% of treated animals. In the current studies, we investigated the mechanism of tumor killing in responding animals and the efficacy of ...

    Also Ranks for: Adenoviral Vectors |  experimental mice mice |  il2 il12 |  treated animals |  combination treatment
    KOL Index score: 11387

    DNA of human adenoviruses 2 and 5 was cleaved by the restriction endonucleases HsuI, BamHI, HpaI, and SmaI. The resulting fragments were separated and tested for their ability to transform primary baby rat kidney (BRK) cells, using the calcium technique. Fragments with transforming activity were obtained with endo's R·EcoRI (fragments A), BamHI (fragments B of Ad2 and A of Ad5 DNA), and HsuI (fragments G). The transforming fragments all represented the left terminal fragments of the ...

    Also Ranks for: Transforming Activity |  5 dna |  viral genes |  human antigens |  adenovirus 2
    KOL Index score: 11153

    Stimulation of antitumor immune mechanisms is the primary goal of cancer immunotherapy, and accumulating evidence suggests that effective alteration of the host-tumor relationship involves immunomodulating cytokines and also the presence of costimulatory molecules. To examine the antitumor effect of direct in vivo gene transfer of murine interleukin 12 (IL-12) and B7-1 into tumors, we developed an adenovirus (Ad) vector, AdIL12-B7-1, that encodes the two IL-12 subunits in early region 1 ...

    Also Ranks for: Tumor Regression |  b7 1 |  experimental mice mice |  mammary neoplasms |  adenovirus vector


    Frank L Graham: Influence Statistics

    Sample of concepts for which Frank L Graham is among the top experts in the world.
    Concept World rank
    e1complementing cells #1
    hd vectors #1
    hcmv amounts #1
    0–45 map units #1
    virions kb #1
    virus replication vp7sc #1
    total net reduction #1
    e1 mutations #1
    maximal levels expression #1
    terminal sequences series #1
    numerous plaque isolates #1
    late mrna transcription #1
    daltons cells #1
    infectious bacterial plasmids #1
    p53 496r function #1
    assay transforming activity #1
    vectors glycoprotein gene #1
    enhancer transformed #1
    e1b species #1
    vectors expressing #1
    g418 resistance adcre1 #1
    033 agarose medium #1
    hybrid adenovirus #1
    intratumoral injection viruses #1
    cultured cells chapter #1
    p53 vectors #1
    tgevneutralizing antibodies sites #1
    vectors observation #1
    mutanttransformed lines #1
    45 112 #1
    asepharose techniques #1
    hrg modified virus #1
    293lap13 cell rescue #1
    vivo expression chapter #1
    icp47 transport #1
    ul53 mrna #1
    adadeficient bone marrow #1
    hsvspecific ctls #1
    mediated ornithine #1
    dialysis membrane slits #1
    integrated dna fragment #1
    amounts elafin #1
    clone pxcl #1
    gb gb gene #1
    ad5based adenovirus vectors #1
    helper viruses hdad #1
    helper virus vectors #1
    kidney pronase #1
    e1substituted vectors #1
    oneloxp site #1

    Key People For Gene Transfer

    Top KOLs in the world
    James Michael Wilson
    gene therapy cystic fibrosis aav vectors
    Ronald G Crystal
    gene transfer alveolar macrophages cystic fibrosis
    A Dusty Miller
    gene transfer retroviral vectors jaagsiekte sheep retrovirus
    Mark A Kay
    gene transfer mouse liver aav vectors
    Richard C Mulligan
    gene transfer stem cells bone marrow
    Inder M Verma
    lentiviral vectors gene therapy fos protein

    Frank L Graham:Expert Impact

    Concepts for whichFrank L Grahamhas direct influence:Gene transfer,  Adenovirus vectors,  Adenoviral vectors,  Gene expression,  Gene therapy,  Adenovirus type,  Human adenovirus,  Adenovirus vector.

    Frank L Graham:KOL impact

    Concepts related to the work of other authors for whichfor which Frank L Graham has influence:Gene therapy,  Cell lines,  Pulmonary fibrosis,  Simplex virus,  Growth factor,  Adenoviral vectors,  Viral dna.



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    Department of Biology, McMaster University, Hamilton, Ontario, Canada | Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada | Department of Pathology and Molecular Medicine, McMaster University, 1200 Main St