ABSTRACT
The nomenclature and the lack of consensus of clinical evaluation and imaging assessment in groin pain generate significant confusion in this field. The Groin Pain Syndrome Italian Consensus Conference has been organised in order to prepare a consensus document regarding taxonomy, clinical evaluation and imaging assessment for groin pain. A 1-day Consensus Conference was organised on 5 February 2016, in Milan (Italy). 41 Italian experts with different backgrounds participated in the discussion. A consensus document previously drafted was discussed, eventually modified, and finally approved by all members of the Consensus Conference. Unanimous consensus was reached concerning: (1) taxonomy (2) clinical evaluation and (3) imaging assessment. The synthesis of these 3 points is included in this paper. The Groin Pain Syndrome Italian Consensus Conference reached a consensus on three main points concerning the groin pain syndrome assessment, in an attempt to clarify this challenging medical problem.
ABSTRACT
The transcription factor p53 regulates the expression of genes crucial for biological processes such as cell proliferation, metabolism, cell repair, senescence and apoptosis. Activation of p53 also suppresses neoplastic transformations, thereby inhibiting the growth of mutated and/or damaged cells. p53-binding proteins, such as mouse double minute 2 homolog (MDM2), inhibit p53 activation and thus regulate p53-mediated stress responses. Here, we found that long glucocorticoid-induced leucine zipper (L-GILZ), a recently identified isoform of GILZ, activates p53 and that the overexpression of L-GILZ in p53(+/+) HCT116 human colorectal carcinoma cells suppresses the growth of xenografts in mice. In the presence of both p53 and MDM2, L-GILZ binds preferentially to MDM2 and interferes with p53/MDM2 complex formation, making p53 available for downstream gene activation. Consistent with this finding, L-GILZ induced p21 and p53 upregulated modulator of apoptosis (PUMA) expression only in p53(+/+) cells, while L-GILZ silencing reversed the anti-proliferative activity of dexamethasone as well as expression of p53, p21 and PUMA. Furthermore, L-GILZ stabilizes p53 proteins by decreasing p53 ubiquitination and increasing MDM2 ubiquitination. These findings reveal L-GILZ as a regulator of p53 and a candidate for new therapeutic anti-cancer strategies for tumors associated with p53 deregulation.
Subject(s)
Proto-Oncogene Proteins c-mdm2/metabolism , Transcription Factors/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Cell Line, Tumor , HEK293 Cells , Humans , Male , Mice , Mice, Knockout , Protein Stability , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-mdm2/genetics , Transcription Factors/genetics , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , Ubiquitination/geneticsABSTRACT
This study was designed to evaluate the efficacy and tolerability of recombinant leukocyte interferon alfa-2a (Hoffmann-LaRoche) as single agent in patients with histologically confirmed Mycosis Fungoides. The protocol consisted of a 12 week induction with subcutaneous interferon, escalating from 3 up to 18 million units daily, and a 6 or 9 month maintenance phase for complete or partial responses, respectively, with 18 million units 3 times weekly. 12 patients are evaluable: 5 are in complete remissions, 6 are partial remissions, and one had disease progression. Alfa-2a interferon was well tolerated: only 3 patients had WHO grade IV organ toxicity. Our study documents that recombinant leukocyte alfa 2a is a highly active agent in untreated patients with Mycosis Fungoides. Finally, the dose schedule chosen in this study allows alfa-2a interferon administration on an outpatient basis.
