ABSTRACT. We compared serum levels of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, matrix metalloproteinase (MMP)-1, and MMP-3 in patients with different stages of knee osteoarthritis (OA), and investigated the clinical significance of diagnosing OA in early stages. OA patients were divided into 2 groups: early OA group (44 cases), intermediate and advanced OA group (26 cases). The healthy control group included 30 samples. ADAMTS-4, ADAMTS-5, MMP-1, and MMP-3 levels in the serum were tested using an enzyme-linked immunosorbent assay. A protein-protein interaction network was constructed by seeding the significantly expressed marker, followed by Gene Ontology enrichment analyses using Database for Annotation, Visualization and Integrated Discovery. ADAMTS-4 levels were significantly higher in patients at early stages of OA compared to intermediate or advanced OA and healthy controls. ADAMTS-5, MMP-1, and MMP-3 levels in intermediate and advanced-stage OA patients were significantly higher than those in early-stage OA patients and healthy controls. The proteinprotein interaction network showed that ADAMTS-4 participates in
The aim of the study was to assess the association between total flavonoids/flavonoid subclasses intake and prostate cancer risk. Several databases were searched to select eligible studies with predefined criteria. Risk ratios (RRs) with 95% confidence intervals (CIs) were used as the effect size. Publication bias and sensitivity analysis were performed. A total of five studies including four prospective cohort studies and one case-control study were included in the meta-analysis. The pooled result demonstrated a significantly increased risk of prostate cancer with higher intake of total flavonoids (RR = 1.12, 95% CI: 1.02-1.23, P = 0.013). However, sensitivity analysis indicated that there lacked a significant association after removing the study of Wang et al. (RR = 1.17, 95% CI: 0.94-1.46). Subgroup analysis stratified by flavonoids subclasses found that higher intake of anthocyanidins and flavan-3-ols were significantly associated with increased prostate cancer risk (RR = 1.12, 95% CI: 1.03-1.21, P = 0.011; RR = 1.21, 95% CI: 1.10-1.32, P < 0.001). Sensitivity analysis also indicated that after removing Wang's study, no significant association between anthocyanidins intake and prostate cancer risk was detected (RR = 1.22, 95% CI: 0.97-1.54). In conclusion, higher intake of flavonoids may not be associated with prostate cancer risk.
Background Pertuzumab and trastuzumab (P and H; F. Hoffmann-La Roche Ltd, Basel, CH) bind to distinct HER2 subdomains and have complementary modes of anticancer activity in HER2-positive breast cancer (BC). A global Phase II study (NeoSphere) reported that neoadjuvant treatment with P+H+docetaxel (D) significantly increased breast pathologic complete response (bpCR) vs H+D in patients (pts) with early/locally advanced/inflammatory HER2-positive BC (Gianni et al. Lancet Oncol 2012). PEONY (NCT02586025), a randomized, multicenter, double-blind, placebo-controlled, Phase III trial conducted in an Asian population (mainland China, Taiwan, Korea, Thailand), primarily compared the efficacy, safety, and tolerability of P+H+D vs placebo (Pla)+H+D in the neoadjuvant setting. We present data from the primary analysis. Methods Pts with centrally confirmed HER2-positive early (T2–3, N0–1)/locally advanced (T2–3, N2 or N3; T4, any N) BC were randomized 2:1 to 4 cycles of P+H+D or Pla+H+D every 3 weeks, before surgery: P, 840 mg loading/420 mg maintenance doses (or Pla); H, 8 mg/kg loading/6 mg/kg maintenance; D, 75 mg/m2. Post-surgery, pts received 3 cycles of fluorouracil, epirubicin, and cyclophosphamide followed by 13 cycles of P+H or Pla+H for up to 1 year (total of 17 HER2-targeted therapy cycles). The primary endpoint was total pCR rate (tpCR; absence of any residual invasive cancer in the breast and lymph nodes [ypT0/is, ypN0]) assessed by independent review committee (IRC) when pts completed surgery with a tpCR assessment. Missing/invalid assessments were considered residual disease. Results A total of 329 pts were randomized: 219 to P, 110 to Pla. Baseline characteristics were well balanced. Most pts had early BC (69.6%) and were from mainland China (79.3%). In the intention-to-treat population, the tpCR rate by IRC was 39.3% in the P arm and 21.8% in the Pla arm; a clinically and statistically significant difference of 17.5% (95% CI 6.9–28.0; p=0.0014). The local pathologist-assessed tpCR rates were 39.3% and 20.9%, respectively. A consistent treatment benefit of P vs Pla was observed in subgroups. Incidences of grade ≥3 adverse events (Aes) were 48.6% in the P arm and 41.8% in the Pla arm. Of the most common grade 3 Aes (≥3% of pts), neutropenia was higher in the P arm (38.1% vs 32.7%). Of the most common any-grade Aes (≥5%), diarrhea was higher in the P arm (38.5% vs 16.4%). No heart failure (New York Heart Association Functional Classification III or IV) or significant left ventricular ejection fraction decline events (≥10 percentage points from baseline and to <50%) were observed during neoadjuvant therapy. Conclusions PEONY met its primary endpoint: P+H+D resulted in a clinically meaningful and statistically significant improvement in the tpCR rate by IRC vs Pla+H+D for the neoadjuvant treatment of HER2-positive early/locally advanced BC in Asian pts. Safety data were in line with the known P safety profile and generally comparable between treatment arms. Results were similar to NeoSphere, and confirm that P+H+D provides superior anticancer activity to H+D alone. Citation Format: Shao Z, Pang D, Yang H, Li W, Wang S, Cui S, Liao N, Wang Y, Wang C, Chang Y-C, Wang H, Kang SY, Jiang Z, Li J, Zhou J, Althaus B, Mao Y, Eng-Wong J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive early or locally advanced breast cancer in the neoadjuvant setting: Efficacy and safety analysis of a randomized phase III study in Asian patients (PEONY) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-17.
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