efficient-recombinant-parvovirus-production-with-help-adenovirus

Efficient Recombinant Parvovirus Production with the Help of Adenovirus-derived Systems

Rodent parvoviruses (PV) such as rat H-1PV and MVM, are small icosahedral, single stranded, DNA viruses. Their genome includes two promoters P4 and P38 ...

A novel family of small proteins, termed p14.5 or YERO57c/YJGFc, has been identified. Independent studies indicate that p14.5 family members are multifunctional proteins involved in several pathways, e.g. regulation of translation or activation of the protease mu-calpain. We have previously shown that Mmf1p, a p14.5 of the budding yeast Saccharomyces cerevisiae, is localized in the mitochondria and influences mitochondrial DNA stability. In addition, we have demonstrated that Mmf1p is functionally related to p14.5 of mammalian cells. To explore further the evolutionary conservation of the mitochondrial function(s) of the p14.5s we have extended our study to the fission yeast, Schizosaccharomyces pombe. In this organism two p14.5 homologous proteins are present: Pmf1p (pombe mitochondrial factor 1) and Hpm1p (homologous Pmf1p factor 1). We have generated a specific Pmf1p antibody, which recognizes a single band of approximately 15 kDa in total cellular extracts. Cellular fractionation experiments indicate that Pmf1p localizes in the mitochondria as well as in the cytoplasm. We also show that Pmf1p shares several properties of S. cerevisiae Mmf1p. Indeed, Pmf1p restores the wild-type phenotype when expressed in delta mmf1 S. cerevisiae cells. Deletion of the leader sequence of Pmf1p abrogates its ability to localize in mitochondria and to functionally replace Mmf1p. Thus, these data together with our previous study show that the mitochondrial function(s) of the p14.5 family members are highly conserved in eukaryotic cells.

Schizosaccharomyces pombe Pmf1p is structurally and functionally related to Mmf1p of Saccharomyces cerevisiae.

Schizosaccharomyces pombe Pmf1p ist strukturell und funktionell Mmf1p von Saccharomyces cerevisiae passt.

Regulation of gene expression is particularly important for gene dosage-dependent diseases and the phenomenon of clinical heterogeneity frequently associated with these phenotypes. We here report on the combined transcriptional and translational regulatory mechanisms controlling the expression of the LÃ©ri-Weill and Turner syndrome gene SHOX. We define an alternative promotor within exon 2 of the SHOX gene by transient transfections of mono- and bicistronic reporter constructs and demonstrate substantial differences in the translation efficiency of the mRNAs transcribed from these alternative promotors by in vitro translation assays and direct mRNA transfections into different cell lines. Although transcripts generated from the intragenic promotor (P2) are translated with high efficiencies, mRNA originating from the upstream promotor (P1) exhibit significant translation inhibitory effects due to seven AUG codons upstream of the main open reading frame (uAUGs). Site-directed mutagenesis of these uAUGs confers full translation efficiency to reporter mRNAs in different cell lines and after injection of Xenopus embryos. In conclusion, our data support a model where functional SHOX protein levels are regulated by a combination of transcriptional and translational control mechanisms.

Transcriptional and translational regulation of the Leri-Weill and Turner syndrome homeobox gene SHOX.

Transkriptionelle und translationale Regulation des Leri-Weill und Turner-Syndrom Hom&#xF6;oboxgens SHOX.

Mutations in the homeobox gene SHOX cause growth retardation and the skeletal abnormalities associated with LÃ©ri-Weill, Langer, and Turner syndromes. Little is known about the mechanism underlying these SHOX-related inherited disorders of bone formation. Here we demonstrate that SHOX expression in osteogenic stable cell lines, primary oral fibroblasts, and primary chondrocytes leads to cell cycle arrest and apoptosis. These events are associated with alterations in the expression of several cellular genes, including pRB, p53, and the cyclin kinase inhibitors p21(Cip1) and p27(Kip1). A SHOX mutant, such as seen in LÃ©ri-Weill syndrome patients, does not display these activities of the wild type protein. We have also shown that endogenous SHOX is mainly expressed in hypertrophic/apoptotic chondrocytes of the growth plate, strongly suggesting that the protein plays a direct role in regulating the differentiation of these cells. This study provides the first insight into the biological function of SHOX as regulator of cellular proliferation and viability and relates these cellular events to the phenotypic consequences of SHOX deficiency.

The short stature homeodomain protein SHOX induces cellular growth arrest and apoptosis and is expressed in human growth plate chondrocytes.

Der Kleinwuchs Hom&#xF6;odom&#xE4;ne Protein induziert SHOX Zellwachstum und Apoptose und wird im menschlichen Wachstums Platte Chondrozyten exprimiert.

Members of the YERO57c/YJGFc/UK114 protein family have been identified in bacteria and eukaryotes. The budding yeast Saccharomyces cerevisiae contains two different proteins of this family, Hmf1p and Mmf1p. We have previously shown that Mmf1p is a mitochondrial protein functionally related to its human homologue and able to influence the maintenance of mitochondrial DNA. Deletion of Mmf1 results in loss of the mitochondrial genome. Using a multicopy suppression approach, we have identified a protein of the mitochondrial large ribosomal subunit, MRPL40, which stabilizes mtDNA in Deltammf1 cells. Overexpression of MRPL40 did not prevent loss of mtDNA in a mutant strain lacking the mitochondrial protein Abf2p. Thus, MRPL40 does not have a general effect on mtDNA stability, but it may be specific for the mmf1-null strain. We also show that the Deltamrpl40 cells present a similar phenotype to the mmf1-null strain, having reduced mtDNA stability and growth rate. Furthermore, we observed that rho(+)Deltamrpl40 haploid cells can be obtained when tetrads are directly dissected on medium containing a non-fermentable carbon source. Thus, replication and segregation of the mtDNA can occur in the absence of MRPL40. We also show that another mitochondrial ribosomal protein, MRPL38, is able to overcome the Deltammf1-associated defect. Together, our results suggest a link between Mmf1p and the two mitochondrial ribosomal proteins.

High levels of the mitochondrial large ribosomal subunit protein 40 prevent loss of mitochondrial DNA in null mmf1 Saccharomyces cerevisiae cells.

Hohe Konzentrationen des mitochondrialen gro&#xDF;en ribosomalen Untereinheit Protein 40 zu verhindern Verlust der mitochondrialen DNA in null mmf1 Saccharomyces cerevisiae-Zellen.

We report the characterization of the nuclear localization signal (NLS) of the short stature homeobox gene SHOX. Mutations within the SHOX gene cause LÃ©ri-Weill dyschondrosteosis (LWD) and Langer mesomelic dysplasia (LD) as well as idiopathic short stature (ISS). Furthermore, haploinsufficiency of SHOX has also been implicated in Turner syndrome. SHOX has been shown to be a cell-type-specific transcriptional activator that localizes to the nucleus. The SHOX protein contains a central homeodomain that together with its transactivation domain regulates the transcription of its target sequences within the nucleus. The sequences for its nuclear localization have not been identified yet. Experimental characterization of SHOX-NLS by deletion mapping identified a non-classic type basic signal, AKCRK, in the recognition helix of the homeodomain. Fusion of this stretch of five amino acids to a cytoplasmic reporter protein resulted in its nuclear translocation. Functional analysis of a missense mutation R173C (C517T) affecting the identified SHOX-NLS in two families with LWS and LD showed that the mutated SHOX protein is unable to enter the nucleus. Conversely, we can demonstrate that insertion of the identified signal adjacent to the mutant site can restore its nuclear translocation. These results establish impairment of nuclear localization as a mechanistic basis for SHOX-related diseases.

Impairment of SHOX nuclear localization as a cause for LÃ©ri-Weill syndrome.

Wertminderung von SHOX Kernlokalisierung als Ursache f&#xFC;r L&#xE9;ri-Weill-Syndrom.

Ver&#xE4;nderung der DNA-Bindung, Dimerisierung, und nukle&#xE4;re Translokation von SHOX-Mutationen in Hom&#xF6;odom&#xE4;ne idiopathischen Kleinwuchs und Leri-Weill Dyschondrosteose identifiziert.

Haploinsufficiency of the short stature homeobox gene SHOX has been found in patients with idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis (LWD). In addition to complete gene deletions and nonsense mutations, several missense mutations have been identified in both patient groups, leading to amino acid substitutions in the SHOX protein. The majority of missense mutations were found to accumulate in the region encoding the highly conserved homeodomain of the paired-like type. In this report, we investigated nine different amino acid exchanges in the homeodomain of SHOX patients with ISS and LWD. We were able show that these mutations cause an alteration of the biological function of SHOX by loss of DNA binding, reduced dimerization ability, and/or impaired nuclear translocation. Additionally, one of the mutations (c.458G>T, p.R153L) is defective in transcriptional activation even though it is still able to bind to DNA, dimerize, and translocate to the nucleus. Thus, we demonstrate that single missense mutations in the homeodomain fundamentally impair SHOX key functions, thereby leading to the phenotype observed in patients with LWD and ISS.

Alteration of DNA binding, dimerization, and nuclear translocation of SHOX homeodomain mutations identified in idiopathic short stature and Leri-Weill dyschondrosteosis.

Mutations within the homeobox SHOX gene have been associated with short stature and the skeletal deformities found in LÃ©ri-Weill, Turner and Langer syndromes implying an involvement of SHOX in growth and bone formation. Despite its clinical significance, the precise role of SHOX and the mechanisms that modulate its functions remain unknown. We reported previously that SHOX is a nuclear protein that specifically binds DNA and acts as a transcriptional activator. We have shown that ectopic expression of SHOX leads to cell-cycle arrest and apoptosis in osteosarcoma and primary cells. To further characterize SHOX, we investigated whether the protein could be a target for phosphorylation. Here, we report that SHOX is phosphorylated exclusively on serine residues in vivo. Two-dimensional phospho-peptide mapping showed that SHOX is phosphorylated to various extents on multiple sites. Site-directed mutagenesis demonstrated that serine 106 is the major SHOX phosphorylation site. We show also that casein kinase II phosphorylates SHOX on serine 106 efficiently in vitro and specific casein kinase II inhibitors reduce SHOX phosphorylation strongly in vivo. Finally, we provide evidence that phosphorylation may play an important role in modulating SHOX biological activities, since a S106A SHOX mutant, defective in phosphorylation, does not activate transcription and fails to induce cell-cycle arrest and apoptosis.

Phosphorylation on Ser106 modulates the cellular functions of the SHOX homeodomain protein.

Short stature due to SHOX deficiency represents a common congenital form of growth failure and is involved in the aetiology of 'idiopathic' short stature and the growth deficits and skeletal anomalies in Leri-Weill, Langer and Turner syndromes. Although much is known on the clinical and molecular aspects of SHOX haploinsufficiency, the integration of SHOX in the signalling pathways regulating bone growth is currently not defined. Here we identify NPPB encoding the natriuretic peptide, BNP, a well-known cardiac and natriuretic peptide hormone, as a transcriptional target of SHOX. The ability of SHOX to transactivate the NPPB endogenous promoter was demonstrated in luciferase reporter assays using serial deletions of the NPPB promotor region. Binding of SHOX to the NPPB promoter was also demonstrated in vivo by chromatin fixation and immunoprecipitation. We also demonstrate the lack of promoter activation in two SHOX mutants from patients with Leri-Weill syndrome. In addition, immunohistochemical analysis of human growth plate sections showed for the first time a co-expression of BNP and SHOX in late proliferative and hypertrophic chondrocytes. Together these data strongly suggest that BNP represents a direct target of SHOX.

BNP is a transcriptional target of the short stature homeobox gene SHOX.

Kleinwuchs SHOX-Mangel stellt eine h&auml;ufige angeborene Form der Minderwuchs und engagiert sich in der &Auml;tiologie der &#39;idiopathische&#39; Kleinwuchs und Wachstum Defizite und Skelettanomalien in Leri-Weill, Langer und Turner-Syndrom. Obwohl viel &uuml;ber die klinische und Molekulare Aspekte der SHOX Haploinsuffizienz bekannt ist, ist die Integration von SHOX in die Signalwege regulieren Knochenwachstum derzeit nicht definiert. Hier erkennen wir NPPB natriuretisches Peptid, BNP, einem bekannten Herz- und natriuretisches Peptid-Hormon, als transkriptionelle Ziel von SHOX-Codierung. Die F&auml;higkeit der SHOX, endogenen Projekttr&auml;ger NPPB transactivate zeigte sich bei Luciferase Reporter-Assays mit serielle L&ouml;schungen der NPPB-promotor-Region. Bindung von SHOX an der NPPB Projekttr&auml;ger auch in-vivo Chromatin Fixierung und Immunopr&auml;zipitation zeigte. Wir zeigen auch das Fehlen der Projekttr&auml;ger Aktivierung in zwei SHOX-Mutanten von Patienten mit Leri-Weill-Syndrom. Dar&uuml;ber hinaus zeigte Immunohistochemical Analyse der menschlichen Wachstum Platte Abschnitte zum ersten Mal eine Koexpression von BNP und SHOX in sp&auml;ten proliferativen und hypertropher Chondrozyten. Diese Daten empfehle zusammen, dass BNP das unmittelbare Ziel von SHOX darstellt.

BNP ist ein transkriptionelle Ziel Kleinwuchs Homeobox Gen SHOX.

The Short Stature Homeobox-containing Gene SHOX was identified as the genetic cause of the short stature phenotype in patients with Turner Syndrome and in certain patients with idiopathic short stature. Shortly after, SHOX mutations were also associated with the growth failure and skeletal deformities seen in patients with LÃ©ri - Weill dyschondrosteosis and Langer mesomelic dysplasia. Today it is estimated that SHOX mutations occur with an incidence of roughly 1:1,000 in newborns, making mutations of this gene one of the most common genetic defects leading to growth failure in humans. This review summarises the involvement of SHOX in several short stature syndromes and describes recent advances in our understanding of SHOX functions and regulation. We also discuss the current evidence in the literature that points to a role of this protein in growth and bone development. These studies have improved our knowledge of the SHOX gene and protein functions, and have given insight into the etiopathogenesis of short stature. However, the exact role of SHOX in bone development still remains elusive and poses the next major challenge for researchers in this field.

SHOX at a glance: from gene to protein.

Der kurze Statur Homeobox-haltigen Gene SHOX wurde als die genetische Ursache des Ph&auml;notyps Kleinwuchs bei Patienten mit Turner-Syndrom und bei bestimmten Patienten mit idiopathischer Kleinwuchs identifiziert. Kurz darauf waren die SHOX Mutationen auch Minderwuchs und Skelettdeformit&auml;ten gesehen bei Patienten mit L&eacute;ri - Weill-Dyschondrosteose und Langer, mesomeler, zugeordnet. Heute wird gesch&auml;tzt, dass SHOX Mutationen mit einer Inzidenz von etwa Tonwert bei Neugeborenen, und Mutationen in diesem Gen ist einer der h&auml;ufigsten genetische Defekte, die zu Wachstum Fehler beim Menschen auftreten. Diesen Bericht fasst die Einbeziehung der SHOX in mehreren Kleinwuchs-Syndromen und beschreibt die j&uuml;ngsten Fortschritte im Verst&auml;ndnis von SHOX-Funktionen und Verordnung. Wir diskutieren auch die aktuelle Hinweise in der Literatur, die auf eine Rolle dieses Proteins in Wachstum und Knochen-Entwicklung zeigt. Diese Studien haben haben unser Wissen &uuml;ber die SHOX-Gen und Protein-Funktionen verbessert, und Einblick in die &Auml;tiopathogenese des Kleinwuchs. Die genaue Rolle von SHOX in Knochen-Entwicklung bleibt jedoch noch und stellt die n&auml;chste gro&szlig;e Herausforderung f&uuml;r Forscher auf diesem Gebiet.

SHOX im &Atilde;&oelig;berblick: vom Gen zum Protein.

The rat parvovirus H-1 (H-1PV) attracts high attention as an anticancer agent, because it is not pathogenic for humans and has oncotropic and oncosuppressive properties. The viral nonstructural NS1 protein is thought to mediate H-1PV cytotoxicity, but its exact contribution to this process remains undefined. In this study, we analyzed the effects of the H-1PV NS1 protein on human cell proliferation and cell viability. We show that NS1 expression is sufficient to induce the accumulation of cells in G(2) phase, apoptosis via caspase 9 and 3 activation, and cell lysis. Similarly, cells infected with wild-type H-1PV arrest in G(2) phase and undergo apoptosis. Furthermore, we also show that both expression of NS1 and H-1PV infection lead to higher levels of intracellular reactive oxygen species (ROS), associated with DNA double-strand breaks. Antioxidant treatment reduces ROS levels and strongly decreases NS1- and virus-induced DNA damage, cell cycle arrest, and apoptosis, indicating that NS1-induced ROS are important mediators of H-1PV cytotoxicity.

Through its nonstructural protein NS1, parvovirus H-1 induces apoptosis via accumulation of reactive oxygen species.

Die Ratte Parvovirus H-1 (H-1PV) zieht hohe Aufmerksamkeit als Anti-Krebs-Agent, weil es nicht pathogen f&uuml;r den Menschen ist und Oncotropic und Oncosuppressive Eigenschaften. Das virale nonstructural NS1-Protein wird angenommen, dass H-1PV Zytotoxizit&auml;t zu vermitteln, aber seine genaue Beitrag zu diesem Prozess bleibt undefiniert. In dieser Studie analysierten wir die Auswirkungen der H-1PV NS1-Protein auf menschliche Zellproliferation und Zellviabilit&auml;t. Wir zeigen, dass NS1 Ausdruck ausreicht, um die Ansammlung von Zellen in Fassung Phase, Apoptose durch Caspase 9 und 3 Aktivierung und Zellenzerst&ouml;rung induzieren. Ebenso mit Wildtyp H-1PV infizierte Zellen in Fassung Phase zu verhaften und Apoptose zu unterziehen. Dar&uuml;ber hinaus zeigen wir auch, dass beide Ausdruck NS1 und H-1PV Infektion f&uuml;hren zu h&ouml;heren Ebenen des intrazellul&auml;ren reaktive Sauerstoffspezies (ROS), DNA-Doppel-Strang-Pausen zugeordnet. Antioxidative Behandlung reduziert ROS Ebenen und stark verringert, NS1 und Virus-induzierte DNA-Sch&auml;den, Zellzyklus Verhaftung und Apoptosis, darauf hinweist, dass NS1-induzierte ROS wichtige Mediatoren der H-1PV Zytotoxizit&auml;t sind.

Durch seine nonstructural Protein NS1 induziert Parvovirus H-1 Apoptosis &uuml;ber Anh&auml;ufung reaktiver Sauerstoffspezies.

The effect of combining sodium butyrate (NaB), a histone deacetylase inhibitor, and 7-hydroxy-staurosporine (UCN-01) on cytotoxicity in human cervical carcinoma cells was evaluated.

Sodium butyrate with UCN-01 has marked antitumour activity against cervical cancer cells.

Die Wirkung der Kombination von Natrium-Butyrat (NaB), ein Histon Deacetylase Inhibitor und 7-hydroxy-Staurosporine (UCN-01) auf Zytotoxizit&auml;t in menschlichen zervikalen Karzinom-Zellen ausgewertet wurde.

Natrium-Butyrat mit UCN-01 hat Antitumor-Aktivit&auml;t gegen Geb&auml;rmutterhalskrebs Zellen markiert.

The rat parvovirus H-1PV is a promising anticancer agent given its oncosuppressive properties and the absence of known side effects in humans. H-1PV replicates preferentially in transformed cells, but the virus can enter both normal and cancer cells. Uptake by normal cells sequesters a significant portion of the administered viral dose away from the tumor target. Hence, targeting H-1PV entry specifically to tumor cells is important to increase the efficacy of parvovirus-based treatments. In this study, we first found that sialic acid plays a key role in H-1PV entry. We then genetically engineered the H-1PV capsid to improve its affinity for human tumor cells. By analogy with the resolved crystal structure of the closely related parvovirus minute virus of mice, we developed an in silico three-dimensional (3D) model of the H-1PV wild-type capsid. Based on this model, we identified putative amino acids involved in cell membrane recognition and virus entry at the level of the 2-fold axis of symmetry of the capsid, within the so-called dimple region. In situ mutagenesis of these residues significantly reduced the binding and entry of H-1PV into permissive cells. We then engineered an entry-deficient viral capsid and inserted a cyclic RGD-4C peptide at the level of its 3-fold axis spike. This peptide binds Î±(v)Î²(3) and Î±(v)Î²(5) integrins, which are overexpressed in cancer cells and growing blood vessels. The insertion of the peptide rescued viral infectivity toward cells overexpressing Î±(v)Î²(5) integrins, resulting in the efficient killing of these cells by the reengineered virus. This work demonstrates that H-1PV can be genetically retargeted through the modification of its capsid, showing great promise for a more efficient use of this virus in cancer therapy.

Retargeting of rat parvovirus H-1PV to cancer cells through genetic engineering of the viral capsid.

Die Ratte-Parvovirus H-1PV ist eine vielversprechende Anti-Krebs-Agent seine Oncosuppressive Eigenschaften und das Fehlen von bekannten Nebenwirkungen beim Menschen gegeben. H-1PV repliziert bevorzugt in transformierten Zellen, aber das Virus kann sowohl Normal als auch Krebs Zellen eingeben. Aufnahme von normalen Zellen Sequester einen erheblichen Teil der viralen administrierten Dosis vom Tumor vorbei. Folglich ist es wichtig, die Wirkung einer Parvovirus-basierte Behandlung zu erh&ouml;hen, Ausrichtung auf H-1PV Eintrag speziell auf Tumorzellen. In dieser Studie fanden wir zuerst die Sialins&auml;ure spielt eine Schl&uuml;sselrolle im H-1PV-Eintrag. Wir entwickelt dann genetisch das H-1PV Kapsid seine Affinit&auml;t f&uuml;r menschliche Tumorzellen zu verbessern. In Anlehnung an die aufgel&ouml;sten Kristallstruktur des eng verwandte Parvovirus Minute Virus von M&auml;usen, entwickelten wir eine in Silico dreidimensionale (3D) Modell der H-1PV Wildtyp Kapsid. Auf der Grundlage dieses Modells wurden vermeintliche Aminos&auml;uren Zellmembran Anerkennung und Virus-Eintrag auf der Ebene der 2-fold Achse der Symmetrie der das Kapsid, innerhalb der sogenannten Gr&uuml;bchen-Region beteiligt. In-situ Mutagenese dieser R&uuml;ckst&auml;nde deutlich reduziert, die Bindung und das Inkrafttreten des H-1PV permissive Zellen. Dann entwickelt ein Eintrag-defizienten virale Kapsid und ein zyklischer RGD - 4 C-Peptid auf der Ebene einer seiner 3-Band-Achse-Spitze eingef&uuml;gt. Dieses Peptid bindet &alpha;(v)&beta;(3) und &alpha;(v)&beta;(5)-Integrine, die in Krebszellen und wachsende Blutgef&auml;&szlig;e Pleuramesotheliom sind. Die Einf&uuml;gung des Peptids gerettet virale Infektiosit&auml;t in Richtung &alpha;(v)&beta;(5)-Integrine, wodurch die effiziente T&ouml;tung dieser Zellen durch das &uuml;berarbeitete Virus &uuml;berexprimierenden Zellen. Diese Arbeit zeigt, dass H-1PV genetisch durch die Modifizierung von seiner Kapsid umgeleitet werden kann, zeigen viel versprechend f&uuml;r eine effizientere Nutzung dieses Virus in der Krebstherapie.

Article	Year
Schizosaccharomyces pombe Pmf1p is structurally and functionally related to Mmf1p of Saccharomyces cerevisiae. Yeast (Chichester, England)\| PubMed ID: 12185840	2002
Transcriptional and translational regulation of the Leri-Weill and Turner syndrome homeobox gene SHOX. The Journal of biological chemistry\| PubMed ID: 12960152	2003
The short stature homeodomain protein SHOX induces cellular growth arrest and apoptosis and is expressed in human growth plate chondrocytes. The Journal of biological chemistry\| PubMed ID: 15145945	2004
High levels of the mitochondrial large ribosomal subunit protein 40 prevent loss of mitochondrial DNA in null mmf1 Saccharomyces cerevisiae cells. Yeast (Chichester, England)\| PubMed ID: 15164357	2004
Impairment of SHOX nuclear localization as a cause for LÃ©ri-Weill syndrome. Journal of cell science\| PubMed ID: 15173321	2004
Alteration of DNA binding, dimerization, and nuclear translocation of SHOX homeodomain mutations identified in idiopathic short stature and Leri-Weill dyschondrosteosis. Human mutation\| PubMed ID: 15931687	2005
Phosphorylation on Ser106 modulates the cellular functions of the SHOX homeodomain protein. Journal of molecular biology\| PubMed ID: 16325853	2006
BNP is a transcriptional target of the short stature homeobox gene SHOX. Human molecular genetics\| PubMed ID: 17881654	2007
SHOX at a glance: from gene to protein. Archives of physiology and biochemistry\| PubMed ID: 17922307	2007
Through its nonstructural protein NS1, parvovirus H-1 induces apoptosis via accumulation of reactive oxygen species. Journal of virology\| PubMed ID: 20375165	2010
Sodium butyrate with UCN-01 has marked antitumour activity against cervical cancer cells. Anticancer research\| PubMed ID: 21036719	2010
Retargeting of rat parvovirus H-1PV to cancer cells through genetic engineering of the viral capsid. Journal of virology\| PubMed ID: 22258256	2012

Antonio Marchini

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