BACKGROUND: Recent genetic studies have implicated p53 mutation as a significant risk factor for therapeutic failure in squamous cell carcinoma of the head and neck (SCCHN). However, in a recent meta-analysis in the literature of p53 from major anatomical subsites (larynx, oral cavity, oropharynx/hypopharynx), associations between patient survival and p53 status were ambiguous. METHODS: The authors examined a cohort of SCCHNs using a previously developed biomarker combination that likely predicts p53 status based on p53/MDM2 expression levels determined by immunohistochemistry (IHC). In addition, the authors generated and validated an antibody to MTBP (an MDM2 binding protein that alters p53/MDM2 homeostasis and may contribute to metastatic suppression) and have incorporated data for MTBP expression into the current analyses. RESULTS: Analysis of expression data for p53 and MDM2 in 198 SCCHN patient samples revealed that the biomarker combination p53 þ ve/MDM2-low (likely indicative of p53 mutation) was significantly associated with reduced overall survival (log-rank P ¼ .035) and was an independent prognostic factor (P ¼ .013; HR, 1.705; 95% CI, 1.12-2.60); thus, these data were compatible with earlier genetic analyses. By using IHC for p53 and MDM2 to dichotomize patients, the authors found that loss of MTBP expression was significantly associated with reduced survival (log-rank P ¼ .004) and was an independent prognostic factor (P ¼ .004; HR, 2.78; 95% CI, 1.39-5.54) in p53 þ ve/MDM2-low patients. CONCLUSIONS: These results represent the first examination of MTBP expression in human tissues and provide evidence for a p53 status-dependent role for MTBP in suppressing disease progression in SCCHN patients as well as confirming a role for p53 pathway function in delaying disease progression.
This report describes the case of a mucinous cystadenocarcinoma of probable urachal origin that presented with mass effect, precipitating deep venous thrombosis and pulmonary embolism. The patient presented with acute symptoms of leg swelling, pain and dyspnoea, and a vague awareness of lower abdominal distension. Computer tomography showed a cystic mass closely related to the anterior abdominal wall and the superior aspect of the bladder. A 1500 cm3cyst adherent to the dome of the urinary bladder was resected on laparotomy. Partial cystectomy was not carried out in the belief that the cyst represented a benign lesion. Subsequent imaging has shown cystic changes in the anterior bladder wall, and the patient has been referred for partial cystectomy.
Inspiration in medical humanities can be intense and personal, and does not necessarily require the portrayal of health issues.
The immunological processes behind sepsis are ill defined. Predicting or diagnosing sepsis, based on cellular immune parameters is a research priority. This study quantified differences in peripheral blood mononuclear cell (PBMC) and cytokine levels between septic patients with fecal peritonitis, matched surgical patients (no sepsis) and healthy controls. To assess function, PBMC were stimulated in vitro with anti-CD3±anti-CD28 antibodies. Four days later T and B cell proliferation were measured by CFSE and activation by expression of CD25 and CD69 on T cells and CD86 on B cells. Viability was assessed by flow cytometry. Concentrations of a range of cytokines were determined from plasma and supernatants (post-stimulation) by multiplex cytometric bead array. On day of phlebotomy there were reduced CD4+ and increased CD19+ cells in septic patients. Plasma IL-6 and IL-8 levels were higher in septic patients, IFN-γ and IL-13 were lower. There was reduced proliferation and activation of T cells from septic patients in response to anti-CD3+anti-CD28. Supernatant levels of IFN-γ, TNF-α and interleukins 1β, 5, 6, 13 and 17A were lower in septic patient samples. There were no initial differences in PBMC viability, but septic patient PBMC had reduced survival on incubation. In summary, we found reduced T cell numbers and a functional impairment of remaining T cells in septic patients.To our knowledge this is the first report of an immune function assay across these three groups.
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