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1.  Gene Expression Profile of Patients with Mayer-Rokitansky-Küster-Hauser Syndrome: New Insights into the Potential Role of Developmental Pathways 
PLoS ONE  2014;9(3):e91010.
Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a rare disease characterized by congenital aplasia of uterus and vagina. Although many studies have investigated several candidate genes, up to now none of them seem to be responsible for the aetiology of the syndrome. In our study, we identified differences in gene expression profile of in vitro cultured vaginal tissue of MRHKS patients using whole-genome microarray analysis. A group of eight out of sixteen MRKHS patients that underwent reconstruction of neovagina with an autologous in vitro cultured vaginal tissue were subjected to microarray analysis and compared with five healthy controls. Results obtained by array were confirmed by qRT-PCR and further extended to other eight MRKHS patients. Gene profiling of MRKHS patients delineated 275 differentially expressed genes, of which 133 downregulated and 142 upregulated. We selected six deregulated genes (MUC1, HOXC8, HOXB2, HOXB5, JAG1 and DLL1) on the basis of their fold change, their differential expression in most patients and their relevant role in embryological development. All patients showed upregulation of MUC1, while HOXB2 and HOXB5 were downregulated, as well as Notch ligands JAG1 and DLL1 in the majority of them. Interestingly, HOXC8 was significantly upregulated in 47% of patients, with a differential expression only in MRKHS type I patients. Taken together, our results highlighted the dysregulation of developmental genes, thus suggesting a potential alteration of networks involved in the formation of the female reproductive tract and providing a useful clue for understanding the pathophysiology of MRKHS.
PMCID: PMC3946625  PMID: 24608967
3.  First case of isolated vaginal metastasis from breast cancer treated by surgery 
BMC Cancer  2012;12:479.
Breast cancer is a leading cause of death in developed countries. This neoplasm frequently relapses at distant sites such as bone, lung, pleura, brain and liver but rarely in the lower female genital tract.
Case presentation
We present the first case of isolated vaginal breast cancer metastasis and its surgical treatment.
This case report focuses on the importance of an accurate genital tract examination as part of regular follow up in breast cancer survivors. Indeed, after this experience we feel that surgery could be considered a valid option for the treatment of an isolated vaginal metastasis.
PMCID: PMC3495020  PMID: 23075305
Breast cancer; Radical surgery; Vaginal metastasis
4.  Monoclonal Antibodies in Gynecological Cancer: A Critical Point of View 
During the last decades, several improvements in treating gynecological malignancies have been achieved. In particular, target therapies, mostly monoclonal antibodies, have emerged as an attractive option for the treatment of these malignancies. In fact, various molecular-targeted agents have been developed for a variety of malignancies with the objective to interfere with a precise tumor associated receptor, essential for cancer cell survival or proliferation, blocking its function, of the cancer cells. Alternatively, monoclonal antibodies have been developed to block immune suppression or enhance functions of immune effector cells. So far, several monoclonal antibodies have been tested for clinical efficacy for the treatment of gynecological cancers. Antibodies against Vascular Endothelial Growth Factor (VEGF) and Epidermal Growth Factor Receptor (EGFR) have been used in different neoplasms such as ovarian and cervical cancer. Catumazumab, a bivalent antibody against CD3 and EpCAM, is effective in the treatment of neoplastic ascites. Other antibodies are peculiar for specific cancer-associated antigen such as Oregovomab against CA125 or Farletuzumab against the folate receptor. Here we describe the preclinical and clinical experience gained up to now with monoclonal antibodies in tumors of the female genital tract and trace future therapeutic and research venues.
PMCID: PMC3253445  PMID: 22235224
5.  HER2-based recombinant immunogen to target DCs through FcγRs for cancer immunotherapy 
Dendritic cell (DC)-based immunotherapy is an attractive approach to induce long lasting antitumor effector cells aiming to control cancer progression. DC targeting is a critical step in the design of DC vaccines in order to optimize delivery and processing of the antigen, and several receptors have been characterized for this purpose. In this study, we employed the FcγRs to target DCs both in vitro and in vivo. We designed a recombinant molecule (HER2-Fc) composed of the immunogenic sequence of the human tumor-associated antigen HER2 (aa 364–391) and the Fc domain of a human IgG1. In a mouse model, HER2-Fc cDNA vaccination activated significant T cell-mediated immune responses towards HER2 peptide epitopes as detected by IFN-γ ELIspot and induced longer tumor latency as compared to Ctrl-Fc-vaccinated control mice. Human in vitro studies indicated that the recombinant HER2-Fc immunogen efficiently targeted human DCs through the FcγRs resulting in protein cross-processing and in the activation of autologous HER2-specific CD8+ T cells from breast cancer patients.
Electronic supplementary material
The online version of this article (doi:10.1007/s00109-011-0794-7) contains supplementary material, which is available to authorized users.
PMCID: PMC3218291  PMID: 21845448
Dendritic cells; Cancer immunotherapy; HER2; Antigen processing; FcγR; Dendritic cell targeting
6.  Immune Effects of Trastuzumab 
Journal of Cancer  2011;2:317-323.
Trastuzumab's targeted therapy has become a stronghold for human epidermal growth factor receptor 2 positive breast cancer patients. This humanized monoclonal antibody binds to the extracellular juxta-membrane domain of HER2 and inhibits the proliferation and survival of HER2 dependent cancer cells. The ways by which this molecule exerts its action have been partially elucidated but several new mechanisms are being constantly identified. Several new agents are being introduced that interfere with HER2. Several new immunotherapy strategies are being introduced in order to direct the immune system against cells and tissues that aberrantly overexpressed HER2. We review the strategies currently adopted and those suggested against HER2 expressing tumors.
PMCID: PMC3119394  PMID: 21716848
autologous cells vaccines; Trastuzumab; HER2; Lapatinib; allo-vesicles

Results 1-6 (6)