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PurposeHypoxia, which is a loss of oxygen in tissues, is a common condition in solid tumors due to the tumor outgrowing existing vasculature. Under hypoxic conditions, hypoxia-inducible factor (HIF)-1α rapidly accumulates and transactivates hundreds of genes, such as matrix metalloproteinases (MMPs). MMPs contribute to invasion and metastasis of tumor cells by degrading the surrounding basement membrane and extracellular matrix barriers, which enables the easy migration and spread of cancer cells. We examined whether hypoxia increases tumor cell invasion, and whether increased invasiveness was due to HIF-1α and MMP-9 expression.MethodsTranswell invasion assays were performed to demonstrate whether hypoxia enhance tumor invasion by use of MDA-MB-231 breast cancer cells. An immunofluorescence assay was used to demonstrate expression of HIF-1α and MMP-9 under hypoxic conditions. Luciferase and ChiP assays were performed to demonstrate that MMP-9 promoter activity was regulated by HIF-1α.ResultsHIF-1α was stabilized under hypoxic conditions and stimulated MMP-9 expression, which affected the tumor invasiveness of breast cancer cells. HIF-1α transactivated the MMP-9 promoter by forming a transcriptional unit with p300, thus increasing expression of MMP-9 transcripts. Zymography indicated that MMP-9 had more gelatinase activity under hypoxic conditions than normoxic conditions. Furthermore, the small GTPase Ras was also activated in response to hypoxia, which then aids stabilization of HIF-1α, and in turn upregulates MMP-9 expression. We also demonstrate that MMP-9 is upregulated concurrently with HIF-1α in tumor tissues from patients with breast cancer.ConclusionThese results suggest that HIF-1α promotes cell invasion through a MMP-9-dependent mechanism and that future antitumor agents could be used to target HIF-1α and MMP-9.

Background There is an increasing interest in HER2-low breast cancer with promising data from clinical trials using novel anti-HER2 antibody–drug conjugates. We explored the differences in clinicopathological characteristics and survival outcomes between HER2-low and HER2-IHC 0 breast cancer. Methods Using nationwide data from the Korean Breast Cancer Registry between 2006 and 2011, 30,491 patients with stages I to III breast cancer were included in the analysis: 9,506 (31.2%) in the HER2-low group and 20,985 (68.8%) in the HER2-IHC 0 group. Kaplan–Meier and Cox proportional hazards regression survival analysis were used to compare breast cancer-specific survival between the two groups. Results HER2-low breast cancer was more frequent in patients with hormone receptor-positive breast cancer than in those with triple-negative breast cancer. In patients with hormone receptor-positive breast cancer, HER2-low breast cancer was associated with fewer T4 tumors, higher histological grade, and a negative lymphatic invasion. In patients with triple-negative breast cancer, HER2-low breast cancer was associated with a high lymph node ratio and positive lymphatic invasion. HER2-low breast cancer was significantly associated with a lower Ki-67 labeling index. No significant difference was observed in overall survival between the two groups. HER2-low breast cancer showed significantly better breast cancer-specific survival than HER2-IHC 0 breast cancer, regardless of the hormone receptor status. In multivariate analysis, the impact of low HER2 expression on breast cancer-specific survival was significant only in triple-negative breast cancer (HRs, 0.68; 95% CI, 0.49–0.93; P = 0.019). Conclusions These findings suggest that the biology and clinical impact of low HER2 expression can differ according to the hormone receptor status and support the need for further investigation on the understanding of the biology of HER2-low breast cancer.

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BackgroundThe purpose of this study was to compare the surgical outcomes of robotic thyroidectomy (RT) using bilateral axillo-breast approach (BABA) with conventional open thyroidectomy (OT) in papillary thyroid carcinoma patients.MethodsBetween January 2009 and December 2013, 815 patients who had received thyroidectomy for papillary thyroid carcinoma were enrolled. Of these, 126 patients received RT and 689 patients underwent OT. Age, gender, body mass index, extent of surgery, tumor size, multiplicity, bilaterality, extrathyroidal extension, and tumor stage were used for the propensity score matching analysis. One hundred and nine patients were selected in each group, and surgical outcomes were compared between the two groups.ResultsThe RT group showed a significantly longer operating time (290.6 ± 74.4 vs. 107.9 ± 30.8 min, P < 0.001). However, the mean hospital stay after surgery (3.6 ± 0.8 vs. 3.4 ± 1.2 days, P = 0.293), postoperative complication rates (major and minor, P = 0.754 and P = 0.852), and pain score (postoperative day, P = 0.669; postoperative day 1, P = 0.952) were comparable between the two groups. There was no difference in the number of metastatic lymph nodes, but the mean number of retrieved lymph nodes in the RT group was lesser than that in the OT group (3.5 ± 3.5 vs. 5.3 ± 5.2, P = 0.002).ConclusionsRobotic thyroidectomy via the BABA may be a safe and acceptable surgical technique. But, further development that resolves the limitation of central node dissection is needed.