Se Eun Park, Won Jun Kim, Sung Woo Park, Ji Woo Park, Namseok Lee, Cheol-Young Park, and Byung-Soo Youn
Angiotensin-converting enzyme 2 (ACE2) plays an important role in glucose metabolism and renal function. However, the relationship between ACE2 and hyperglycemia or microalbuminuria has not been established in humans. We investigated whether urinary ACE2 levels are associated with abnormal glucose homeostasis and urinary albumin excretion.
We developed an ELISA for quantifying ACE2 in urine. The ELISA was used to measure urinary ACE2 levels in 621 subjects with: normal glucose tolerance (NGT; n=77); impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) (n=132); and type 2 diabetes mellitus (T2DM, n=412). Insulin resistance was assessed by homeostasis model assessment for insulin resistance (HOMA-IR) index and urinary albumin excretion by urine albumin-to-creatinine ratio (ACR). Other biochemical and anthropometric parameters were measured.
Urinary ACE2 levels were significantly higher in insulin-resistant subjects with IFG, IGT, and T2DM than in the NGT group (P<0.001). Urinary ACE2 concentrations appeared to correlate with HOMA-IR, fasting blood glucose, triglyceride, high-sensitivity C-reactive protein, serum creatinine, urinary ACR, and systolic blood pressure (all P<0.05). After adjustment for impaired renal function and other metabolic parameters, urinary ACE2 concentration was still associated with a higher risk for T2DM (OR 1.80, 95% CI 1.05–3.08, P=0.02). In addition, urinary ACE2 levels were highly predictive of microalbuminuria after adjusting for clinical risk factors (OR 2.68, 95% CI 1.55–4.64, P<0.001).
Our data suggest that the urinary ACE2 level is closely associated with T2DM and is an independent risk factor for microalbuminuria.
Jun Park, Hyun Ae Jung, Joon Ho Shim, Woong-Yang Park, Tae Hyuk Kim, Se-Hoon Lee, Sun Wook Kim, Myung-Ju Ahn, Keunchil Park, and Jae Hoon Chung
Anaplastic thyroid cancer (ATC) has dismal prognosis and there is no effective treatment. We aimed to evaluate the efficacy of tyrosine kinase inhibitor (TKI) therapy in real-world clinic and to suggest the most effective treatment modality according to the combination of treatments.
This retrospective study evaluated clinical outcomes and cause of death with multimodal treatments in patients with ATC at Samsung Medical Center.
A total of 120 patients received anti-cancer treatment for ATC. Seventy-seven (64.2%) patients underwent surgery, 64 (53.3%) received radiotherapy, 29 (24.2%) received cytotoxic chemotherapy, and 19 (15.8%) received TKI therapy. In the TKI therapy group, eight achieved partial response (three with lenvatinib and five with dabrafenib plus trametinib), and two patients with lenvatinib showed stable disease. Median progression-free survival (PFS) of the TKI therapy group was 2.7 months (range: 0.1–12.7) and their median overall survival (OS) was 12.4 months (range: 1.7–47.7). Patients who received surgery or radiotherapy for local control showed superior OS than those who did not. In a multivariate analysis, surgery, TKI therapy, younger age, and no distant metastasis were associated with favorable OS. The combination of surgery, radiotherapy, and TKI therapy (median OS: 34.3 months, 6-month survival rates: 77.8%) was the most effective. Compared to the era without TKI therapy, distant metastasis has recently become the major cause of death in ATC over airway problems.
Multimodality treatment including TKI therapy demonstrated prolonged survival with dabrafenib plus trametinib as the most effective therapeutic option demonstrated for BRAF mutant ATC patients.