Mouse anti Human TIMP2 monoclonal antibody, clone 238822

Objectives: Despite modern treatment regimens, overall survival in head and neck squamous cell carcinomas (HNSCC) is less than 50% due to local and systemic disease recurrency. The current study aims to identify molecular markers in primary tumor specimens that predict the risk for local and systemic recurrency at the time of initial diagnosis. Methods: The study included clinic-pathological data of 1,057 HNSCC. MMP2/9, TIMP1/2, CXCR4, and CXCL12 immunohistochemistry was done in 150 randomly selected specimens. For statistics, we employed Chi square, Fisher exact, and Student's t-test. Overall survival (OS) was calculated by Kaplan-Meier and log-rank test. Prognostic variables were subsequently evaluated by Cox regression for forward selection. Results: CXCR4 positive specimens demonstrated a significant increased risk for tumor recurrency associated death (rT: HR 10.07; p=0.001 / rN: HR 5.04; p=0.013 / rM: HR 2.49; p=0.029) when compared with their unaltered counterparts. Expression of MMP9, TIMP2, CXCR4, and CXCL12 was significantly increased in distant metastasized patients (p<0.0001) and showed significant cross-correlation. In addition, CXCR4 positivity was associated with an increased risk to die due to enhanced T or N status (T1/2 vs. T3/4: HR 5.78; p=0.017; N0 vs. N+: HR 5.18; p=0.033). Conclusion: CXCR4 positivity in tumor samples at initial diagnosis were associated with reduced overall survival, in particular with respect to increasing T/N status, local and systemic recurrency.

Background: In acute decompensated heart failure (ADHF) the risk of acute kidney injury (AKI) is high. Early detection of patients at risk for AKI is important. We tested urinary [TIMP2] x [IGFBP7], a new US Food and Drug Administration-cleared test to assess AKI risk, in a cohort of hospitalized ADHF patients. Hypothesis: In patients with ADHF, urinary [TIMP-2] x [IGFBP7] is associated with moderate to severe AKI and related to increased mortality. Methods: We enrolled 400 patients in the emergency department at Robert-Bosch Hospital, Stuttgart, Germany. We examined the predictive ability of urinary [TIMP-2] x [IGFBP7] (units: [ng/mL] 2/1000) for development of AKI stage 2 or 3 within 24 hours of sample collection in patients with ADHF. Operating characteristics were determined for the validated cutoffs of 0.3 and 2.0. Results: Forty patients had ADHF upon presentation and sufficient data for AKI staging. 27.5% developed AKI stage 2-3 within 7 days. Urinary [TIMP-2] x [IGFBP7] discriminated for AKI stage 2-3 over the first day with an area under the ROC curve of 0.84 (95% confidence interval: 0.72-0.93) and over 7 days with an AUC of 0.77 (95% confidence interval: 0.65-0.88). For the first day, sensitivity was 86% at the 0.3 cutoff and specificity was 95% at the 2.0 cutoff for prediction of AKI stage 2-3. There was a trend (P = 0.08) for higher mortality in patients with urinary [TIMP-2] x [IGFBP7] >2.0 and AKI 2-3. Conclusions: Urinary [TIMP-2] x [IGFBP7] is a promising marker for AKI risk assessment in patients with ADHF.