University of Naples Federico II

About: University of Naples Federico II is a education organization based out in Naples, Campania, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 29291 authors who have published 68803 publications receiving 1920149 citations. The organization is also known as: Università degli Studi di Napoli Federico II & Naples University.

LY2109761, a novel transforming growth factor β receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis

Abstract: Most pancreatic cancer patients present with inoperable disease or develop metastases after surgery. Conventional therapies are usually ineffective in treating metastatic disease. It is evident that novel therapies remain to be developed. Transforming growth factor β (TGF-β) plays a key role in cancer metastasis, signaling through the TGF-β type I/II receptors (TβRI/II). We hypothesized that targeting TβRI/II kinase activity with the novel inhibitor LY2109761 would suppress pancreatic cancer metastatic processes. The effect of LY2109761 has been evaluated on soft agar growth, migration, invasion using a fibroblast coculture model, and detachment-induced apoptosis (anoikis) by Annexin V flow cytometric analysis. The efficacy of LY2109761 on tumor growth, survival, and reduction of spontaneous metastasis have been evaluated in an orthotopic murine model of metastatic pancreatic cancer expressing both luciferase and green fluorescence proteins (L3.6pl/GLT). To determine whether pancreatic cancer cells or the cells in the liver microenvironment were involved in LY2109761-mediated reduction of liver metastasis, we used a model of experimental liver metastasis. LY2109761 significantly inhibited the L3.6pl/GLT soft agar growth, suppressed both basal and TGF-β1−induced cell migration and invasion, and induced anoikis. In vivo , LY2109761, in combination with gemcitabine, significantly reduced the tumor burden, prolonged survival, and reduced spontaneous abdominal metastases. Results from the experimental liver metastasis models indicate an important role for targeting TβRI/II kinase activity on tumor and liver microenvironment cells in suppressing liver metastasis. Targeting TβRI/II kinase activity on pancreatic cancer cells or the cells of the liver microenvironment represents a novel therapeutic approach to prevent pancreatic cancer metastasis. [Mol Cancer Ther 2008;7(4):829–40]

Extended endoscopic endonasal transsphenoidal approach for the removal of suprasellar tumors: Part 2.

Abstract: Objective The widespread use of the endoscope in transsphenoidal pituitary surgery has recently contributed to the extension of the approach beyond the tuberculum sellae and planum sphenoidale for the management of lesions located in the suprasellar area, either with an endoscope-assisted or purely endoscopic technique Based on our previous experience with more than 450 standard endoscopic transsphenoidal operations, we have retrospectively evaluated the effectiveness of the extended endoscopic endonasal transsphenoidal approach in the management of lesions mainly located in the suprasellar area Methods Between January 2004 and December 2005, 20 consecutive patients underwent extended endoscopic endonasal transsphenoidal surgery for a total of 21 procedures The series consisted of seven pituitary adenomas, seven craniopharyngiomas, three suprasellar Rathke's cleft cysts, two tuberculum sellae meningiomas, and one pilocytic astrocytoma of the chiasm Results Tumor removal, as assessed by postoperative magnetic resonance imaging, revealed complete removal of the lesion in four out of seven pituitary adenomas, five out of seven craniopharyngiomas, three out of three Rathke's cleft cysts, and two out of two tuberculum sellae meningiomas One patient (5%) with craniopharyngioma had a postoperative cerebrospinal fluid leak that required reoperation The same patient experienced a sphenoid mycosis, which was treated with medical therapy Some specific conditions associated with the anatomy of the surgical route, as well as to the morphology of the lesion, have resulted to condition the feasibility of the approach Conclusion Small and medium sized suprasellar lesions located in the midline, with or without a limited parasellar extension and without involvement of vascular structures, seem amenable to be resected through such extended endoscopic transsphenoidal approach Improvements in closure techniques and the use of new materials and surgical glues seem to significantly reduce the postoperative cerebrospinal fluid leak rate and meningitis

Multifunctional CD4(+) T cells correlate with active Mycobacterium tuberculosis infection

Abstract: Th1 CD4+ T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametric flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-γ/IL-2/TNF-α triple expressors, IFN-γ/IL-2, IFN-γ/TNF-α or TNF-α/IL-2 double expressors or IFN-γ, IL-2 or TNF-α single expressors) of CD4+ T cells in individuals with latent M. tuberculosis infection (LTBI) and active tuberculosis (TB). We found that triple expressors, while detectable in 85–90%TB patients, were only present in 10–15% of LTBI subjects. On the contrary, LTBI subjects had significantly higher (12- to 15-fold) proportions of IL-2/IFN-γ double and IFN-γ single expressors as compared with the other CD4+ T-cell subsets. Proportions of the other double or single CD4+ T-cell expressors did not differ between TB and LTBI subjects. These distinct IFN-γ, IL-2 and TNF-α profiles of M. tuberculosis-specific CD4+ T cells seem to be associated with live bacterial loads, as indicated by the decrease in frequency of multifunctional T cells in TB-infected patients after completion of anti-mycobacterial therapy. Our results suggest that phenotypic and functional signatures of CD4+ T cells may serve as immunological correlates of protection and curative host responses, and be a useful tool to monitor the efficacy of anti-mycobacterial therapy.