ABSTRACT
PURPOSE: Very few studies have sought prognostic factors after adrenalectomy for metastasis. The aim of this study was to assess prognostic factors for oncological outcomes after adrenalectomy for adrenal metastasis. METHODS: All adrenalectomies for metastases performed in seven centers between 2006 and 2016 were included in a retrospective study. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Prognostic factors for CSS and RFS were sought by Cox regression analyses. RESULTS: 106 patients were included. The primary tumors were mostly renal (47.7%) and pulmonary (32.3%). RFS and CSS estimated rates at 5 years were 20.7% and 63.7%, respectively. In univariate analysis, tumor size (HR 3.83; p = 0.04) and the metastasis timing (synchronous vs. metachronous; HR 0.47; p = 0.02) were associated with RFS. In multivariate analysis, tumor size (HR 8.28; p = 0.01) and metastasis timing (HR 18.60; p = 0.002) were significant factors for RFS. In univariate analysis, the renal origin of the primary tumor (HR 0.1; p < 0.001) and the disease-free interval (DFI; HR 0.12; p = 0.02) were associated with better CSS, positive surgical margins with poorer CSS (HR 3.4; p = 0.01). In multivariate analysis, the renal origin of the primary tumor vs. pulmonary (HR 0.13; p = 0.03) and vs. other origins (HR 0.10; p = 00.4) and the DFI (HR 0.01; p = 0.009) were prognostic factors for CSS. CONCLUSION: In this study, tumor size and synchronous occurrence of the adrenal metastasis were associated with poorer RFS. Renal origin of the primary tumor and longer DFI were associated with better CSS. These prognostic factors might help for treatment decision in the management of adrenal metastasis.
Subject(s)
Adrenal Gland Neoplasms/secondary , Adrenal Gland Neoplasms/surgery , Adrenalectomy , Metastasectomy/methods , Adrenal Gland Neoplasms/mortality , Aged , Disease-Free Survival , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Survival RateABSTRACT
Restoration of p53 tumor suppressor function through inhibition of its interaction and/or enzymatic activity of its E3 ligase, MDM2, is a promising therapeutic approach to treat cancer. However, because the MDM2 targetome extends beyond p53, MDM2 inhibition may also cause unwanted activation of oncogenic pathways. Accordingly, we identified the microtubule-associated HPIP, a positive regulator of oncogenic AKT signaling, as a novel MDM2 substrate. MDM2-dependent HPIP degradation occurs in breast cancer cells on its phosphorylation by the estrogen-activated kinase TBK1. Importantly, decreasing Mdm2 gene dosage in mouse mammary epithelial cells potentiates estrogen-dependent AKT activation owing to HPIP stabilization. In addition, we identified HPIP as a novel p53 transcriptional target, and pharmacological inhibition of MDM2 causes p53-dependent increase in HPIP transcription and also prevents HPIP degradation by turning off TBK1 activity. Our data indicate that p53 reactivation through MDM2 inhibition may result in ectopic AKT oncogenic activity by maintaining HPIP protein levels.
Subject(s)
Intracellular Signaling Peptides and Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-mdm2/metabolism , Animals , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Drug Resistance, Neoplasm , Estrogen Receptor alpha/metabolism , Estrogens , Female , Humans , MCF-7 Cells , Mice , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Tamoxifen/pharmacology , Tumor Suppressor Protein p53/deficiency , Tumor Suppressor Protein p53/metabolismABSTRACT
The coordination chemistry of model phenolic ligands (pyrocatechol, salicylic acid, and 2,2'-biphenol) that are able to form respectively five-, six-, or seven-membered rings with titanium(IV) alkoxides is investigated. With pyrocatechol, a polynuclear complex containing 10 Ti atoms was characterized with a not very common doubly bridging mu3-(O,O,O',O') coordination mode. With salicylic acid, a monomeric tris(chelate) complex was obtained. With 2,2'-biphenol, a polynuclear complex containing six Ti atoms was obtained showing both mu2-(O,O') and mu2-(O,O,O') coordination modes for the ligands. Intermolecular interactions in the solid state for these three new compounds are also quantitatively discussed using the partial charge model.
Subject(s)
Organometallic Compounds/chemistry , Phenols/chemistry , Salicylates/chemistry , Titanium/chemistry , Catechols/chemical synthesis , Catechols/chemistry , Crystallography, X-Ray , Models, Molecular , Molecular Conformation , Organometallic Compounds/chemical synthesis , Phenols/chemical synthesis , Salicylates/chemical synthesisABSTRACT
A clinical case of epithelioid hemangioma of the scalene muscle that occupied the parapharyngeal space is reported. The patient was a 34 year old man with a 2-month history of sensation of pharyngeal foreign body and mild dysphagia. The exploration revealed a tumor of the posterior and lateral wall of the oropharynx that extended from the rhinopharynx to the hypopharynx. The diagnostic sequence included CT, MRI, Doppler echography, and arteriography, which identified a right post-styloid tumor located behind and medial to the jugular vein, internal carotid artery, and vagal nerve, but did not affect arterial blood flow. The patient underwent surgical treatment consisting of lateral cervicotomy, tumor excision, and histological study.
