Laboratory of biomedical technologies and experimental oncology
Department of human pathology and oncology, division of pathological anatomy
University of Siena
Policlinico S. Maria alle Scotte,
Strada delle Scotte, 6 - 53100 Siena, Italy
Principal investigator: Antonio Giordano
Role of the tumor suppressor Rb2/p130 in gastric cancer
The aim of this research area is to look for cell cycle alterations in gastric cancer. Primary tumors of gastric cancer were collected according to International Gastric Cancer Linkage Consortium (IGCLC) criteria, and they were provided by the Surgical Oncology Section of our Department, with whom we collaborated with on the project. We analyzed the expression of the tumor suppressor gene RB2/p130 in eighteen samples of diffuse gastric cancer, both at the mRNA and protein levels, using quantitative Real time RT-PCR and Western blotting, respectively. It is known from the literature that pRb2/p130 is down-regulated in different types of cancer, such as lung, breast and prostate cancers. Therefore, we were interested in investiging whether its expression may be altered in gastric cancer and, if this is the case, what molecular mechanism underlies this deregulation.
Our results demonstrate that the expression of pRb2/p130 is strongly reduced in about 25% of the cases, as shown in Figure 1, suggesting the involvement of pRb2/p130 in gastric cancer.
Figure 1: Expression level of pRb2/p130 from tumor samples of five patients (N indicates the normal mucosa and T indicates the tumor tissue from the same patient). Normalization was made to actin. Our future objective is to investigate the molecular mechanisms underlying the deregulation of pRb2/p130 expression level in order to elucidate its role in gastric oncogenesis.
Characterization of cell cycle regulation in sporadic Burkitt lymphoma (GAL1).
The World Health Organization Classification of Lymphoid Neoplasms identifies Burkitt lymphoma (BL) as a highly aggressive mature B-cell neoplasm consisting of endemic (eBL), sporadic (sBL), and immunodeficiency-associated (AIDS-related BL) variants. These subtypes share many morphological and immunophenotypical features, but there are differences in their clinical and geographic presentations. However, few sBL cell lines have been submitted to detailed cytogenetic characterization. Recently, a novel sBL cell line was established from a HIV-negative patient with an Epstein-Barr virus (EBV)-negative sporadic BL, presenting as an effusion (Thielen C et al.). This cell line was referred to as GAL1 cells. GAL1 cells display the phenotype and genotype of B-cell lineage (CD20+, CD79+a and presenting clonal rearrangement of the Ig heavy chain), carry the c-myc rearrangement by t(8;22)(q24;q11) translocation and are characterized by the expression of the germinal center-associated antigens CD10, BCL6, CD38 and show low BCL2 expression. Subcutaneous injection of this cell line in mice induced tumor formation. Genetic alterations disrupting the nuclear localization of the retinoblastoma-related gene RB2/p130 have been documented in BL cell lines, as well as in primary tumors. Recently, point mutations of Rb2/p130 have been described as leading to amino acid substitutions in the COOH terminal domain of the protein, namely in the bipartite nuclear localization signal (NLS). Cells bearing such mutations produce a full-length pRb2/p130 molecule, which consistently remains confined to the cytoplasm. The final result is the failure to reach a satisfactory intracellular localization, with a consequent inability to negatively modulate the cell cycle, by physical interference with nuclear transcription factors.
The aim of this research was to evaluate the intracellular distribution of pRb2/p130 in the GAL1 cell line, to assay if this tumor suppressor gene may have a role in the evolution and progression of sBL.
To study subcellular localization of pRb2/p130, immunofluorescence staining in the GALl cell line, using a monoclonal antibody against the NH2-terminal region of pRb2/p130, was performed. As a control of normal nuclear localization of pRb2/p130, a human B-lymphoblastoid cell line, immortalized with EBV, but not transformed (EBV-B), was used. As depicted in Fig. 1, the GAL1 cell line shows prevailing localization of the protein at the cytoplasmic level, whereas EBV-B cells exhibit exclusive nuclear localization of pRb2/p130. This result was further supported by Western blotting analysis after cell fractionation. pRb2/p130 was detected both in the cytoplasm and nucleus, confirming the subcellular localization demonstrated by immunofluorescence staining. To confirm the purity of the cell fractionation, the subcellular fractions were also analyzed by Western blotting with the cytoplasmic marker, ▀-tubulin, and the nuclear marker, Sp1 proteins. As shown in Fig 2, no cross-contaminations between the nuclear and cytoplasmic fractions were observed. In previous studies, cytoplasmic staining of the pRb2/p130 protein was ascribed to a guanosine or a cytosine insertion at exon 21, which caused the loss of the bipartite NLS, resulting from a shift in the coding frame with a consequent stop codon upstream from the NLS. Therefore, a DNA-sequencing analysis of exon 21 was performed. Insertion of an A should this be specified? within the 5' splice site of exon 21 was observed, which may be responsible for the altered expression of pRb2/p130 in this cell line. Sequence variations occurring in exons or introns may affect the correct processivity of the mRNA by disrupting the splice site. These mutations can result in either complete skipping of the exon, retention of the intron, or the introduction of a new splice site within an exon or intron. The effect of this new mutation in influencing pRb2/p130 aberrant cytoplasmatic localization has yet to be proven. However, the same mutation was recently found in a Raj Burkitt lymphoma cell line (De Falco, personal communication) in which pRb2/p130 shows the same sub-cellular localization observed in the GAL1 cell line. Together, these data demonstrate that the insertion of an A within the 5' splice site of exon 21 is involved in the improper cytoplasmic distribution of pRb2/p130, with its consequent functional inactivation. The future aims of this research area will be to prove whether and how this impaired pRb2/p130 localization may be relevant to GAL1 neoplastic transformation and/or may give the cells a more aggressive malignant phenotype.
Fig.1 Immunofluorescence staining in a GAL1 cell line using monoclonal antibodies against the NH2-terminal region of pRb2/ p1
Fig.2 Western blotting analysis of cell fractionation of a GAL1 cell line using the antibody against pRb2/P130, Sp1 and ▀-tubulin, respectively.
Role of Chlamydia psittaci in the genesis of ocular lymphomas
Non-Hodgkin lymphomas (NHLs) are among the most common primary tumors occurring in the ocular adnexa. Ocular adnexal lymphomas (OALs) represent a small fraction of all systemic NHLs (6% of all primary extranodal NHLs, 7% of non-gastric marginal zone lymphomas). However, they are among the most common tumors occurring in the ocular adnexa (26%). These lymphomas may involve any part of the eye socket, including orbit, conjunctiva, lids and the lacrimal gland or sac. OALs can be an initial presentation of NHL, either solitary or systemic, or may represent dissemination of previously diagnosed lymphoma. Furthermore, the etiology of OALs and the reason for the predominance of EMZL specify? in this anatomic location are unknown. EMZL arises in lymphoid tissue acquired through chronic antigenic stimulation because of persistent inflammation or infection, as exemplified by Helicobacter pylori infection in patients with gastric lymphoma, Borrelia burgdorferi and Campylobacter jejuni infections in patients with skin and intestinal MALT specify? lymphomas, respectively, and association of the salivary and thyroid gland MALT lymphomas with Sj÷gren syndrome and Hashimoto thyroiditis. However, the majority of patients with OALs do not report any preceding chronic inflammatory or infection processes in the affected tissues. Interestingly, the presence of Chlamydia psittaci DNA in 80% of the analyzed Italian ocular adnexa EMZL cases was recently reported, thus raising the possibility that this is the etiological pathogen of these tumors.
Primary cases of OALs were obtained by the Department of Oculistics of the University of Siena and the presence of Chlamydia psittaci was then evaluated by nested PCR. Our results show that approximately 20% of the clinical samples were positive for this antigen. We aim to evaluate whether there is any cell cycle regulator alteration in these lymphoma samples. Particulary, whether there is a deregulation of proteins in the pathways regulated by the retinoblastoma family (RB).
Reverse transcriptase inhibitor in human medulloblastoma cells.
Endogenous, non-telomeric reverse transcriptase (RT) is encoded by two classes of repeated elements: retrotransposons and endogenous retroviruses. Expression of RT-coding genes is usually activated in the mammalian germ line, embryonic tissues and tumor cells, whereas it is repressed in differentiated non-pathological tissues. Abacavir is a nucleoside RT inhibitor, with a well characterized inhibitory activity on RT enzymes of a retroviral origin, and it is clinically approved for the treatment of HIV-1 infection in adults and children.
According to its favorable safety profile and lipophilic nature, we analyzed the drug's effects in two human medulloblastoma cell lines, Daoy and D283. Here, we show that Abacavir is able to cause a reduction in the rate of cell growth in cell lines (Figure 1). In our experiments, Abacavir caused neither non-specific cell death nor apoptosis in any tested cell line, as indicated by FACS measurement of cells with hypodiploid DNA content. Thus, the decrease in cell growth reflects progressive withdrawal from the cell cycle. Indeed, the FACS analysis depicted changes in the cell cycle profile: as shown in figure 2. Cells with a S DNA content accumulated in cell cultures after 72 h of Abacavir exposure. In the near future, we aim to unravel the molecular mechanisms underlying the biological effect mediated by Abacavir.
Figure 1: Proliferation rate in Abacavir-treated vs. untreated cell lines
Figure 2: FACS analysis in Abacavir-treated vs. untreated cell lines
- Fondazione Monte dei Paschi di Siena 2004: Ruolo di pRb2/p130 nella genesi del Medulloblastoma: dal meccanismo alla terapia genica (Role of pRb2/130 in the genesis of Medulloblastoma: from mechanism to genic therapy)
- Fondazione Monte dei Paschi di Siena 2006: Ruolo del gene oncosoppressore RB2/p130 nei processi di senescenza e cancro (Role of gene oncosupressor RB2/130 in the processes of senescence and cancer).
- AIRC 2006: ER-transcriptional regulation by RBproteins: prognostic markers and therapeutic targets in breast cancer".
- Claudio P.P., Stiegler P., Howard C.M., Bellan C., Minimo C., Tosi G.M., Rak J., Kovatich A., De Fazio P., Micheli P., Leoncini L., Caputi M., Kerbel R., Giordano GG, and Giordano A. (2001): RB2/p130 gene enhanced expression down-regulates Vascular Epithelial Growth Factor expression and inhibits Angiogenesis in vivo. Cancer Res. 61:462-468.
- Zamparelli A., Masciullo V., Bovicelli A., Santini D., Ferrandina G., Minimo C., Terzano P., Costa S., Cinti C., Ceccarelli C., Mancuso S., Scambia G., Bovicelli L., Giordano A. (2001): Expression of cell-cycle-associated proteins pRB2/p130 and p27 in vulvar squamous cell carcinomas. Human Pathology 32: 4-9
- Testa J.R., Giordano A. (2001): SV40 and cell cycle perturbations in malignant mesothelioma. Semin Cancer Biol. 2001: 31-38.
- Galderisi U., Melone M.A., Jori F.P., Piegari E., Di Bernardo G., Cipollaro M., Cascino A., Peluso G., Claudio P.P., Giordano A. (2001): pRb2/p130 gene overexpression induces astrocyte differentiation. Mol Cell Neurosci 17: 415-425.
- Claudio P.P, Cinti C., Giordano A. (2001): Application of the PRINS technique to titer recombinant virus and evaluation of the efficiency of viral transduction. Anal Biochem. 291:96-101.
- Kasten M, Giordano A. (2001): Cdk10, a Cdc2-related kinase, associates with the Ets2 transcription factor and modulates its transactivation activity. Oncogene. 20(15):1832-8.
- Susini T, Massi D, Paglierani M, Masciullo V, Scambia G, Giordano A, Amunni G, Massi G, Taddei GL. (2001): Related Articles Expression of the retinoblastoma-related gene Rb2/p130 is downregulated in atypical endometrial hyperplasia and adenocarcinoma. Hum Pathol 32: 360-7.
- Fraldi A., Licciardo P., Majello B., Giordano A., Lania L. (2001): Distinct regions of cyclinT1 are required for binding to CDK9 and for recruitment to the HIV-1 Tat/TAR complex. J. Cell. Biochem. 36: 247-253.
- De Luca A., Russo P., Severino A., Baldi A., Battista T., Cavallotti I., De Luca L., Baldi F., Giordano A., Paggi M.G. (2001): Pattern of expression of cyclin T1 in human tissues. Journal Histochem Cytochem 49: 685-692.
- De Luca A., Tosolini A., Russo P., Severino A., Baldi A., De Luca L., Cavallotti I., Baldi F, Giordano A., Testa J.R., and Paggi M.G. (2001): Cyclin T2A gene maps on human chromosome 2q21. Journal Histochem Cytochem 49: 693-698.
- Paggi M.G., Bonetto F., Severino A., Baldi A., Battista T., Bucci F., Felsani A., Lombardi D., Giordano A. (2001): The retinoblastoma-related Rb2/p130 gene is an effector downstream of the AP-2 differentiation program. Oncogene 20: 2570-2578.
- Lombardi D., Palescandolo E., Giordano A., Paggi MG. (2001): Interplay between the antimetastatic nm23 and the Retinoblastoma-related Rb2/p130 genes in promoting neuronal differentiation of PC12 cells. Cell Death & Differ 8:470-476.
- Paggi M.G., Giordano A. (2001): Who is the boss in the Retinoblastoma family? The point of view of Rb2/p130, the little brother. Cancer Research 61: 4651-4654.
- Bovicelli A., >Giordano A. (2001): The RB2/p130 gene: a new player in gynecologic cancer. Women Oncol Rev. 1: 109-115.
- Sang N. , Severino A. , Russo P. , Baldi A. , Giordano A. , Mileo A.M. , Paggi M.G. De Luca A (2001): RACK1 interacts with E1A and rescues E1A-induced yeast growth inhibition and mammalian cell apoptosis. J Biol Chem 276: 27026-27033.
- Claudio, P. P., Cinti, C., Paggi, M. G., Giordano, A. Letters to the Editor. Reply. Cancer Res, 61: 5952-5953, 2001.
- Gan DD, Reiss K., Carrill T., Del Valle L., Croul S., Giordano A., Fishman P., Khalili K. (2001): Involvement of Wnt signaling Pathway in Murine medulloblastoma induced by human neurotropic JC Virus. Oncogene. (2001) 20:4864-70.
- Simone C., Giordano A. (2001) New insight in cdk9 function: from Tat to MyoD: Front. in Biosci. 6: d1073-1082.
- Zini N., Trimarchi C., Claudio P.P., Stiegler P., Marinelli F., Maltarello M.C., La Sala D., De Falco G., Russo G., Ammirati G., Maraldi N.M., Giordano A., Cinti C. (2001): pRb2/p130 and p107 control cell growth by multiple strategies and in association with different compartments within the nucleus. J. Cell. Physiol. 189: 34-44.
- Stiegler P., Giordano A. (2001): The Family of Retinoblastoma Proteins. Critical Reviews in Eukaryotic Gene Expression 11: 69-86.
- Del Valle L., Lorenzana C., Giordano A., Khalili K., Croul S (2001): Expression of a Human Polyomavirus Oncoprotein and Tumor Suppressor Proteins in Medulloblastomas Mol Pathol. 54: 11331-337.
- Puri P.L., Iezzi S., Stiegler P., Chen T.T., Schiltz R.L., Muscat G.E.., Giordano A., Kedes L., Wang J.Y.., Sartorelli V. (2001): Class I Histone Deacetylases sequentially interact with MyoD and pRb during skeletal myogenesis. Mol. Cell 8: 885-97.
- Darbinian N., Sawaya B.E., Khalili K., Jaffe N., Wortman B, Giordano A., Amini S. (2001): Functional interaction between cyclin T/cdk9 and Pur?determines the level of TNF promoter activation by Tat in glial cells. J. of Neuroimmunol. 121: 3-11.
- Zhang D., Vuocolo S., Masciullo V., Sava T., Giordano A., Soprano D.R. Soprano K.J. (2001): Cell Cycle Genes as targets of retinoid induced ovarian tumor cell growth suppression. Oncogene 20:7935-7944.
- Jori F.P., Galderisi U., Piegari E., Peluso G., Cipollaro M., Cascino A., Giordano A. Melone M.A. (2001): Rb2/p130 ectopic gene expression in neuroblastoma stem cells: evidence of cell fate restriction and induction of differentiation. Biochem. J. 360:569-577.
- Gusterson R.., Brar B., Faulkes D., Giordano A., Chrivia J., Latchman D. (2002): CBP and p300 are activated via Phenylephrine through the p42/p44 MAPK cascade. J Biol Chem 277: 2517-2524.
- Yuan W. L., Giordano A. (2002): Acetyltransferase Machinery Conserved in p300/CBP-Family Proteins. Oncogene. 21: 2253-2260.
- Sang N, Caro J, Giordano A. (2002): Adenoviral E1A everlasting tool, versatile applications, continuous contributions and new hypotheses. Frontiers in Bioscience 7:407-413.
- Pagnini U., Florio S.,Crispino L., Pagnini G., Colangelo D., Rocco D., Pacilio C., Pacilio M., Macaluso M. , Giordano A. (2002): Direct effect of a Gonadotropin-Releasing Hormone agonist on the growth of canine mammary tumour cells. J Cell Biochem 85: 470-481
- Simone C., Resta N., Bagella L., Giordano A., Guanti G. (2002): Cyclin E and chromosome instability (CIN) in colorectal cancer. Mol Pathol. 2002. 55: 200-3.
- De Falco G., Giordano A. (2002): CDK9: From Basal Transcription to Cancer and AIDS. Cancer Biol and Therapy 1: 342.347.
- Caputi M., Esposito V., Mancini A., Giordano A.: (2002): Air pollution and respiratory pathology: lung cancer. Monaldi Arch Chest Dis. 57:177-79.
- Claudio PP, Tonini T, Giordano A. (2002): The retinoblastoma family: twins or distant cousins? Genome Biol. 3(9): reviews3012.
- Simone C, Stiegler P, Bagella L, Pucci B, Bellan C, De Falco G, De Luca A, Guanti G, Puri PL, Giordano A. (2002): Activation of MyoD-dependent transcription by cdk9/cyclin T2. Oncogene 21: 4137-4148
- Simone C., Bagella L., Bellan C., Giordano A. (2002): Physical interaction between pRb and cdk9/cyclin T2 complex. Oncogene 21: 4158-65.
- Claudio P.P., Zamparelli A., Garcia F.U., Claudio L., Giuseppe G., Farina A., Bovicelli A., Cusano T., Giordano G.G., Mc Ginnis D.E., Giordano A., Cardi G. (2002): Expression of Cell-Cycle Regulated Proteins pRb2/p130, p107, p27kip1, p53, Mdm-2, and of Ki-67 (MIB-1) in Prostatic Gland Adenocarcinoma. Clin Cancer Res. 8: 1808-15.
- Florio S, Pagnini U, Crispino A, Pacilio C, Crispino L, Giordano A. (2002): GnRH and steroids in cancer. Front Biosci. 7: 1590-608.
- Lazzi S, Bellan C, De Falco G, Cinti C, Ferrari F, Nyongo A, Claudio PP, Tosi GM, Vatti R, Gloghini A, Carbone A, Giordano A, Leoncini L, Tosi P. (2002): Related Expression of RB2/p130 tumor-suppressor gene in AIDS-related non-Hodgkin's lymphomas: Implications for disease pathogenesis. Hum Pathol.: 33:723-731
- Darbinian A., Darbinian A., Safak M., Radhakrishanan S., Giordano A., Khalili K., (2002): Evidence for dysregulation of cell cycle by human polyomavirus, JCV, late auxiliary protein.Oncogene. 21: 5574-81.
- Amini S., Clavo A., Nadraga Y, Giordano A., Khalili K., Sawaya E. B. (2002): Interplay between cdk9 and NF-kappaB factors determines the level of HIV-1 gene transcription in astrocytic cells. Oncogene. 21: 5797-5803.
- De Falco G., Neri L.M., Yu Z., De Luca A., De Falco M., Bellan C., Leoncini L. and Giordano A. (2002): The signal transducer gp130 binds to Cdk9, a member of the cdc2-like family of kinases. Oncogene: 21: 7464-70
- Sano M., Abdellatif M., Oh H., Xie M., Bagella L., Giordano A., Lloyd H. M., DeMayo F. J., Schneider M. D. (2002): Activation and function of cyclin T/cdk9 (positive transcription elongation factor-b) in cardiac muscle cell hypertrophy. Nature Medicine 8: 1310-17.
- Caputi M., Groeger A.M., Esposito V., De Luca A., Masciullo V., Mancini A., Baldi F., Wolner E., Giordano A. (2002): Loss of pRb2/p130 expression is associated with unfavorable clinical outcome in lung cancer. Clinical Cancer Research. 8: 850-56.
- Bellan C., De Falco G., Tosi GM, Lazzi S., Ferrari F., Morbini G., Bartolomei S., Toti P., Mangiavacchi P., Cevenini G., Trimarchi C., Cinti C., Giordano A, Leoncini L., Tosi P., Cottier H. (2002): Missing expression of pRb2/p130 in human retinoblastomas is associated with reduced apoptosis and lesser differentiation. Invest. Ophthal. and Visual Science. 43: 3602-8
- Pucci B, Claudio PP, Masciullo V, Bellincampi L, Terrinoni A, Khalili K, Melino G, Giordano A. (2002): pRb2/p130 promotes radiation-induced cell death in the glioblastoma cell line HJC12 by p73 upregulation and Bcl-2 downregulation. Oncogene. Aug 29;21(38):5897-905.
- Lavia P, Mileo AM, Giordano A, Paggi MG. (2003): Emerging roles of DNA tumor viruses in cell proliferation: new insights into genomic instability. Oncogene. 22(42):6508-16.
- Bellan C., Lazzi S., De Falco G., Nyongo A., Giordano A, Leoncini (2003): Burkitt lymphoma: new insight into molecular pathogenesis. J. Clin. Pathol. 56: 188-192.
- Gallo G., Giarnieri E., Bosco S., Cappelli C., Alderisio M., Giovagnoli MR, Giordano A., Vecchione A.,2003): Aberrant Bcl-2 and Bax protein expression related to chemotherapy response in neuroblastoma. Anticancer Res. 23:777-784.
- De Martino l., Marfe G., Di Stefano C., Pagnini U., Florio S., Crispino L., Iovane G., Macaluso M., Giordano A. (2003): Interference of bovine herpesvirus 1 (BHV-1) in sorbitol- Induced apoptosis. J Cell Biochem. 89: 373-380.
- Macaluso M, Cinti C., Russo G., Russo A., Giordano A. (2003). pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 multimolecolar complexes mediate the transcription of estrogen receptor-α in breast cancer. Oncogene, 22: 3511-3517.
- La Sala D, Macaluso M, Trimarchi C, Giordano A and Cinti C. (2003). Triggering of p73-dependent apoptosis in osteosarcoma is under the control of E2Fs-pRb2/p130 complexes. Oncogene 22: 3518-3529.
- Florio S., Crispino L., Ciarcia R., Vacca G., Pagnini U., de Matteis A., Pacilio C., D'Andrilli G., Kumar C., Giordano A. (2003): MPA increases idarubicin-induced apoptosis in chronic lymphatic leukaemia cells via caspase-3. J Cell Biochem. 89: 747-754.
- Gallo G., Bibbo M., Bagella L., Zamparelli A., Sanseverino F., Giovagnoli MR, Vecchione A., Giordano A. (2003): Study of viral integration of HPV16 in young patients with LSIL. J Clin. Pathol. 56: 532-536.
- Galderisi U., Jori F. P., Giordano A. (2003): Cell Cycle regulation and neural differentiation. Oncogene 22: 5208-5219.
- De Falco G., Bellan C., Lazzi S., Claudio P.P., La Sala D., Cinti C., Tosi P., Giordano A., Leoncini L. (2003): The interaction between HIV-1 Tat and pRb2/p130: a possible mechanism in the pathogenesis of AIDS-related neoplasms. Oncogene 22: 6214-6219.
- Russo G., Zegar C., Giordano A. (2003): Advantages and limitations of microarray technology in human cancer. Oncogene. 22: 6497-507.
- Macaluso M., Paggi M.G., Giordano A. (2003): Genetic and epigenetic alterations as hallmarks of the intricate road to cancer. Oncogene. 22: 6472-8.
- Giordano A., Maio M. (2003): Guest editors.Oncogene. 22 : 6470-1.
- Giordano A., Maio M. (2003): Biomolecular strategies for therapeutic intervention in cancer.Oncogene. 22:6469.
- Russo G., Claudio P.P., Fu Y., Stiegler P., Yu Z., Macaluso M., Giordano A. (2003): pRB2/p130 target genes in non-small lung cancer cells identified by microarrayanalysis.Oncogene. 22; 6959-69.
- Masciullo V, Susini T, Zamparelli A, Bovicelli A, Minimo C, Massi D, Taddei G, Maggiano N, De Iaco P, Ceccaroni M, Bovicelli L, Amunni G, Mancuso S, Scambia G, Giordano A. (2003): Frequent loss of expression of the cyclin-dependent kinase inhibitor p27(Kip1) in estrogen-related Endometrial adenocarcinomas. Clin. Cancer. Res:14:5332-8.
- Sanseverino F., Torricelli M., Petraglia F., Giordano A. (2003): Role of the Retinoblastoma Family in Gynecological Cancer. Cancer Biol and Therapy 6: 636-641
- Romano G., Claudio PP, Tonini T., Giordano A. (2003): Human immunodeficiency virus type 1 (HIV-1) derived vectors: safety considerations and controversy over therapeutic applications. Eur. J. Derm. 13:424-9.
- Jori FP, Galderisi U, Piegari E, Cipollaro M, Cascino A, Peluso G, Cotrufo R, Giordano A, Melone MA. (2003): EGF-responsive rat neural stem cells: molecular follow-up of neuron and astrocyte differentiation in vitro.J Cell Physiol. 195(2):220-33.
- Gan DD, Macaluso M., Cinti C., Khalili K., Giordano A., (2003): How does a normal human cell become a cancer cell? J Exp Clin Cancer Res. 22: 509-516.
- Simone C., Stiegler P., Forcales SV., Bagella L., De Luca A., Sartorelli V., Giordano A., Puri PL. (2004): Deacetylase recruitment by the C/H3 domain of the acetyltransferase p300. Oncogene: 23: 2177-87
- Severino A., Baldi A., Cottone G., Han M., Sang N., Giordano A., Mileo A.M., Paggi M.G., De Luca A. (2004): RACK1 is a functional target of the E1A oncoprotein. J Cell Physiol. 199:134-139
- Pagnini U., Montagnaro S., De Martino L., Florio S., Iovane G., Pacilio M., Gabellini C., Marsili S., Giordano A. (2004): The involvement of oxidative stress in bovine herpesvirus type 4-mediated apoptosis. Frontiers in Bioscience Sept 1;9:2106-14.
- D'Andrilli G., Masciullo V., Bagella L., Tonini T., Minimo C., Zannoni GF, Giuntoli RL, Carlson J. A., Soprano D.R., Soprano KJ, Scambia G., Giordano A. (2004): Frequent loss of pRb2/p130 in human ovarian carcinoma. Clin. Cancer. Res.
- Tonini T., Bagella L., D'Andrilli C., Claudio PP, Giordano A., (2004): Ezh2 reduces the ability of HDAC1-dependent pRb2/p130 transcriptional repression of cyclin A. Oncogene
- Bellan C., De Falco G., Lazzi S., Micheli P., Vicidomini S., Schurfeld K., Amato T., Palumbo A., Bagella L., Sabattini E., Bartolommei S., Hummel M., Pileri S., Tosi P., Leoncini L., Giordano A. (2004): CDK9. Cyclin T1 expression during lymphoid differentiation and malignant transformation. J Clin Path
- Jori FP, Napolitano MA, Melone MA, Cipollaro M, Cascino A, Giordano A, Galderisi U. (2004):Role of RB and RB2/p130 genes in marrow stromal stem cells plasticity.J Cell Physiol. 200: 201-12.
- Claudio PP, Russo G, Kumar CA, Minimo C, Farina A, Tutton S, Nuzzo G, Giuliante F, Angeloni G, Maria V, Vecchio FM, Campli CD, Giordano A. (2004): pRb2/p130, vascular endothelial growth factor, p27(KIP1), and proliferating cell nuclear antigen expression in hepatocellular carcinoma: their clinical significance. Clin Cancer Res. 10: 3509-17.
- Giordano A. Macaluso M. (2004): (Editorial) Prognostic significance of pRb family and p16 (INK4)alterations in colorectal cancer: an interesting point of you in a complex net of molecular signals. Human Pathol. 35:1171-1172.
- Jori FP, Napolitano MA, Melone MA, Cipollaro M, Cascino A, Altucci L., Peluso G., Giordano A, Galderisi U. (2004): Molecular pathways involved in neural in vitro differentiation of marrow stromal stem cells. J Cell Biochem.
- Wang J.Y. , Del Valle F., Peruzzi F., Trojanek A., Giordano A., Khalili K., Reiss K.(2004): Polyomaviruses and Cancer - Interplay between viral proteins and signal transduction Pathways. J Exp Clin Cancer Res. 23: 373-383.
- Sang N, Fath DM, Giordano A. (2004): A gene highly expressed in tumor cells encodes novel structure proteins. Oncogene 23: 9438-9446.
- D'Andrilli G, Kumar C, Scambia G, Giordano A. (2004): Cell cycle genes in ovarian cancer: steps toward earlier diagnosis and novel therapies. Clin Cancer Res 10: 8132-8141.
- Tonini T., Gabellini C., Bagella L., D'Andrilli G, Masciullo V., Romano G., Scambia G., Zupi G., Giordano A. (2004): pRb2/p130 decrease sensitivity to apoptosis induced by camptothecin and doxorubicin but not by taxol. Clin Cancer Res 10: 8085-93.
- Montanari M, Boninsegna A, Faraglia B, Coco C, Giordano A, Cittadini A, Sgambato A. (2005): Increased expression of geminin stimulates the growth of mammary epithelial cells and is a frequent event in human tumors. J Cell Physiol. 202: 215-22.
- Jori FP, Melone MA, Napolitano MA, Cipollaro M, Cascino A, Giordano A, Galderisi U. (2005):RB and RB2/p130 genes demonstrate both specific and overlapping functions during the early steps of in vitro neural differentiation of marrow stromal stem cells. Cell Death Differ. 12: 65-77
- Normanno N., De Luca A., Maiello M.R., Mario Mancino, Antonio D'Antonio, Marcella Macaluso, Francesco Caponigro and Giordano A. (2005): Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors In Breast Cancer: Current Status and Future Development. Frontiers in Bioscience.
- Russo G, Zamparelli A, Howard CM, Minimo C, Bellan C, Carillo G, Califano L, Leoncini L, Giordano A, Claudio PP.(2005): Expression of cell cycle-regulated proteins pRB2/p130, p107, E2F4, p27, and pCNA in salivary gland tumors: prognostic and diagnostic implications. Clin Cancer Res
- Mischitelli M, Fioriti D, Videtta M, Degener AM, Antinori A, Cinque P, Giordano A, Pietropaolo V., (2005): Investigation on the role of cell transcriptional factor Sp1 and HIV-1 TAT protein in PML onset or development. J Cell Physiol Sep;204 (3): 913-8
- Caraglia M, Marra M, Mancinelli F, D'ambrosio G, Massa R, Giordano A, Budillon A, Abbruzzese A, Bismuto E.,(2005): Electromagnetic fields at mobile phone frequency induce apoptosis and inactivation of the multi-chaperone complex in human epidermoid cancer cells. J Cell Physiol Mar 7
- Fioriti D, Videtta M, Mischitelli M, Degener AM, Russo G, Giordano A, Pietropaolo V.,(2005): The human polyomavirus BK: Potential role in cancer. J Cell Physiol Feb 2
- De Falco G, Bellan C, D'Amuri A, Angeloni G, Leucci E, Giordano A, Leoncini L.,(2005): Cdk9 Regulates Neural Differentiation and Its Expression Correlates with the Differentiation Grade of Neuroblastoma and PNET Tumors. Cancer Biol Ther Mar 20
- Macaluso M, Montanari M, and Giordano A., (2005): The regulation of ER-x transcription by pRb2/p130 in breast cancer. Annals of Oncology. May; 16 Suppl 4:iv20-iv22
- Sanseverino F, D'Andrilli G, Petraglia F, Giordano A. (2005): Molecular pathology of ovarian cancer. Anal Quant Cytol Histol. Jun;27 (3):121-4.
- Cinti C, Macaluso M and Giordano A., (2005): Tumor-specific exon 1 mutations could be the 'hit event' predisposing Rb2/p130 gene to epigenetic silencing in lung cancer.Oncogene. Sep 1;24(38):5821-6.
- Tosi G.M., Trimarchi C., Macaluso M., La Sala D., Ciccodicola A., Lazzi L., Massaro Giordano M., Caporossi A., Giordano A., Cinti C. (2005): Genetic and epigenetic alterations of RB2/p130 tumor suppressor gene in human sporadic retinoblastoma: implication for Pathogenesis and therapeutic approach. Oncogene. Sep 1;24(38): 5827-36.
- Normanno N, Di Maio M, De Maio E, De Luca A, de Matteis A, Giordano A, Perrone F; NCI-Naple Breast Cancer Group. (2005): Mechanisms of endocrine resistance and novel therapeutic strategies in breast cancer.Endocr Relat Cancer. Dec;12(4):721-47.
- Gallo G, Giordano A. (2005): Are RB proteins a potential substrate of Pin1 in the regulation of the cell cycle? J Cell Physiology. Nov;205 (2):176-81
- Macaluso M, Montanari M, Cinti C, Giordano A.(2005) Modulation of cell cycle components by epigenetic and genetic events. Semin Oncol. Oct;32(5):452-7
- Caputi M, Russo G, Esposito V, Mancini A, Giordano A. (2005) Role of cell-cycle regulators in lung cancer. J Cell Physiol.; 205( 3) :319-27.
- Galderisi U, Cipollaro M, Giordano A. (2006): Stem cells and brain cancer. Cell Death Differ. Jan;13(1):5-11.
- Sanseverino F, Santopietro R, Torricelli M, D'Andrilli G, Russo G, Cevenini G, Bovicelli A, Leoncini L, Scambia G, Petraglia F, Claudio PP, Giordano A. (2006) pRb2/p130 and VEGF Expression in Endometrial Carcinoma in Relation to Angiogenesis and Histopathologic Tumor Grade. Cancer Biol Ther. Jan;5(1):84-8.
- Giacinti L, Claudio PP, Lopez M, Giordano A. (2006): Epigenetic information and estrogen receptor alpha expression in breast cancer. Oncologist. Jan;11 (1):1-8.
- Purev E., Giordano A.,Soprano D., Soprano K,.(2006): Interaction of PP2A Catalytic Subunit with Rd/p130 is required for All-trans Retinoic Acid Suppression of Ovarian Carcinoma Cell Growth. J Cell Physiol. Feb;206(2): 495-502
- Reiss K, Khalili K, Giordano A, Trojanek J. (2006): JC virus large T-antigen and IGF-I signaling system merge to affect DNA repair and genomic integrity. J Cell Physiol. Feb; 206 (2):295-300.
- Merola E, Claudio PP, Giordano A. (2006): p53 and the malignant progression of Barrett's esophagus. J Cell Physiol. Mar; 206 (3):574-7.
- Giacinti C, Bagella L, Puri PL, Giordano A, Simone C. (2006): MyoD recruits the cdk9/cyclin T2 complex on myogenic-genes regulatory regions. J Cell Physiol. Mar;206(3):807-13.
- Trojanek J, Ho T, Croul S, Wang JY, Chintapalli J, Koptyra M, Giordano A, Khalili K, Reiss K.(2006): IRS-1-Rad51 nuclear interaction sensitizes JCV T-antigen positive medulloblastoma cells to genotoxic treatment. Int J Cancer. Mar 29
- Vogiatzi P, De Falco G, Claudio PP, Giordano A. (2006): How Does the Human RUNX3 Gene Induce Apoptosis in Gastric Cancer?: Latest Data, Reflections and Reactions. Cancer Biol Ther. Apr 30; 5(4)
- Merola E, Mattioli E, Minimo C, Zuo W, Rabitti C, Cicala M, Caviglia R, Pollice L, Gabbrielli A, Giordano A, Claudio PP. (2006): Immunohistochemical evaluation of pRb2/p130, VEGF, EZH2, p53, p16, p21waf-1, p27, and PCNA in Barrett's esophagus. J Cell Physiol. May; 207 512-9.
- Giordano A., Andreotti G. Tramice A., Trincone A, (2006) Marine glycosyl hydrolases in the hydrolysis and synthesis of oligosaccharides; Biotechnol J. May; 1 (5): 511-30
- Giordano A, Andreotti G, Tramice A, Trincone A, (2006) Marine glycosyl hydrolases in the hydrolysis and synthesis of oligosaccharides. Biotechnol J. 2006 May;1(5):511-30.
- Bin Shi, Marco Prisco, George Calin, Chang-gong Liu, Giuseppe Russo, Antonio Giordano and Renato Baserga. (2006) "Expression profiles of micro RNA in proliferating and differentiating 32D murine myeloid cells". Journal Cellular Physiology. (ahead of press)
- Claudio PP, Cui J, Ghafouri M, Mariano C, White MK, Sarak M, Sheffield JB, Giordano A, Khalili K, Amini S, Sawaya BE. (2006) Cdk9 phosphorylates p53 on serine 392 independently of CKII. J Cell Physiol. Jun 1; 208 (3): 602-612
- Bagella L, Giacinti C, Simone C, Giordano A. Identification of murine cdk10: (2006) Association with Ets2 transcription factor and effects on the cell cycle. J Cell Biochem. June 1.
- Bertini A, Giordano A, Varesi P, Villa L, Mancini C, Carattoli A, (2006) First report of the carbapenem-hydrolyzing oxacillinase OXA-58 in acinetobacter baumannii isolates in Italy. Antimicrob Agents Chemother, Jun; 50 (6); 2268-9
- Nyagol J, Leucci E, Onnis A, De Falco G, Tigli C, Sanseverino F, Torriccelli M, Palummo N, Pacenti L, Santopietro R, Spina D, Gichangi P, Muchiri L, Lazzi S, Petraglia, Leoncini L, Giordano A, (2006) The Effects of HIV-1 Tat Protein on Cell Cycle during Cervical Carcinogenesis. Cancer Biol Ther. 2006 Jun; 5(6):684-90. Epub 2006 Jun 18.
- Del Vecchio MT, Epistolato MC, Tripodi SA, Montironi R, Giordano A. (2006) Intratubular germ cell neoplasia of unclassified type. Anal Quant Cytol Histol; Jun; 28 (3) 157-70
- Cascio S, Bartella V, Garofalo C, Russo A, Giordano A, Surmacz E. (2006) Insulin-like growth factor 1 differently regulates estrogen receptor- dependent transcription at ERE and AP-1 sites in Breast Cancer cells. J. Biol Chem. (Ahead of print)
- Simone C., Giordano A. (2006) Aborgation of signal-dependent activation of the cdk9/cyclin t2a complex in human RD rhabdomyosarcoma cells. Cell Death Differ; Jul 14; (Epub ahead of print.)
- Bovicelli A, D'Andrilli G, Giordano A. (2006)Multidisciplinary international conference on gynecologic cancer.J Cell Physiol. Jul; 2081-5.
- Forte A, Napolitano MA, Cipollaro M, Giordano A, Cascino A, Galdersi U. (2006) An effective method for adenoviral-mediated delivery of small interfering RNA into mesenchymal stem cells. J Cell Biochem. 2006 Aug 3; (Epub ahead of print)
- Forte A, Napolitano MA, Cipollaro M, Giordano A, Cascino A, Galdersi U. (2006) An effective method for adenoviral-meditated delivery of small interfering RNA into mesenchymal stem cells. Aug 3; J Cell Biochem.
- Gardner EL, Liu X, Paredes W, Giordano A, Spector J, Lepore M, Wu KM, Froimowitz M. (2006) A slow-onset, long-duration indanamine monoamine reuptake inhibitor as a potential maintenance pharmacotherapy for psychostimulant abuse: Effects in laboratory rat models relating to addiction. Neuropharmacology. 2006 Aug 7; (Epub ahead of print)
- Giancinti C, Giordano A. (2006) RB and cell cycle progression. Oncogene Aug 28; 25 (38); 5220-7
- De Falco G, Giordano A (2006) pRb2/p130: a new candidate for retinoblastoma tumor formation. Oncogene. 2006 Aug 28; 25 (38):5333-40.
- Caracciolo V, Reiss K, Khalili K, De Falco G, Giordano A. (2006) Role of the interaction between large T antigen and Rb family members in the oncogenicity of JC virus. Oncogene. 2006 Aug 28;25 (38):5294-301.
- Macaluso M, Montanari M Giordano A (2006) Rb family proteins as modulators of gene expression and new aspects regarding the interaction with chromatin remodeling enzymes. Oncogene. 2006 Aug 28;25(38):5263-5267.
- Galderisi U, Cipollaro M, Giordano A (2006) The retinoblastoma gene is involved in multiple aspects of stem cell biology. Oncogene. 2006 Aug 28;25(38):5250-5256.
- Giacinti L, Lopez M, Giordano A (2006) Clinical Trails. Front Biosci. Sep 1;11:2918-23.
- Mattioli E., Vogiatzi P., Sun A., Abbadessa G., Angeloni G., D'Ugo D., Trani D., Gaughan J.P., Vecchio F.M., Cevenini G., Persiani R., Giordano A., Claudio P.P.. Immunohistochemical analysis of pRb2/p130, VEGF, EZH2, p53, p16 (INK4A), p27 (KIP1), p21 (WAF1), Ki-67 expression patterns in gsatric cancer. J. Cell. Physiol., 210, 183-191, 2007.
- Trani D., Lucchetti C., Cassone M., D'Agostino L., Caputi M., and Giordano A.. Analysis of cell-cycle regulation following exposure of lung-derived cells to γ-rays. Adv. Space Res., In press, 2007.
- Cassone M, Giordano A, Pozzi G. Bacterial DNA microarrays for clinical microbiologo: the early logarithmic phase. Front. Biosci. 12: 2658-69, 2007.