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Both skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) have been widely adopted. Although postmastectomy radiation therapy (PMRT) can improve clinical outcomes, it can worsen cosmesis following reconstruction. Therefore, identifying risk factors of ipsilateral breast tumor recurrence (IBTR) could help de-escalate PMRT after NSM/SSM in patients with pT1-2 disease. We retrospectively reviewed patients treated with SSM (N = 400) and NSM (N = 156) in patients with pT1-2N0-1 disease between 2009 and 2016. Seventy-four patients received PMRT with 50–50.4 Gy in 25–28 fractions. The Cox proportional hazards model was used to analyze the prognostic factors of IBTR. With a median follow-up of 66.2 months, 17 IBTR events were observed, with 5-year IBTR-free rate of 97.2%. Although only one IBTR was observed after PMRT, there was no statistical difference in the 5-year IBTR-free rate (PMRT vs. no PMRT, 98.6% vs. 97.0%, p = 0.360). Multivariable analyses demonstrated that age ≤45 years and lymphovascular invasion (LVI) were adverse features of IBTR. The low-risk group (0 risk factor) showed a better 5-year IBTR-free rate than the high-risk group (≥1 risk factor) (100.0% vs. 95.8%, p = 0.003). In the high-risk group, PMRT slightly improved 5-year IBTR-free rate compared with no PMRT (98.6% vs. 95.2%, p = 0.166). In addition, PMRT increased 5-year cumulative incidence of reconstruction failure (10.0% vs. 2.8%, p = 0.001). We identified risk factors (age and LVI) related to IBTR following upfront SSM/NSM with pT1-2 disease. As a hypothesis-generating study, de-escalation of PMRT by omitting chest wall irradiation in selective patients could improve reconstruction-related complications without compromising oncologic outcomes. • IBTR-free rate at 5 years after SSM/NSM in pT1-2N0-1 disease was 97.2%. • Age ≤45 years and tumor with LVI were associated with increased IBTR rate. • Omitting chest wall RT to selective patients could improve reconstruction outcomes. [ABSTRACT FROM AUTHOR]

It is important to continually reevaluate the risk/benefit calculus of internal mammary node irradiation (IMNI) in the era of modern systemic therapy. We aimed to investigate the effect of IMNI on survival in node-positive breast cancer treated with mastectomy and anthracycline plus taxane-based chemotherapy. We analyzed 348 patients who underwent mastectomy and anthracycline plus taxane-based chemotherapy for node-positive breast cancer between January 2006 and December 2011. All patients received postoperative radiation therapy (RT) with IMNI (n = 105, 30.2%) or without IMNI (n = 243, 69.8%). The benefit of IMNI for disease-free survival (DFS) and overall survival (OS) was evaluated using multivariate analysis and inverse probability of treatment weighting (IPTW) to adjust for unbalanced covariates between the groups. After a median follow-up of 95 months, the 10-year locoregional recurrence-free survival rate, DFS, and OS in all patients were 94.8%, 77.4%, and 86.2%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of IMNI (vs. no IMNI) with DFS and OS was 0.208 (95% confidence intervals (CI) 0.045–0.966) and 0.460 (95% CI, 0.220–0.962), respectively. In multivariate analysis, IMNI was a favorable factor for DFS (HR, 0.458; P = 0.021) and OS (HR 0.233, P = 0.018). IMNI was associated with improved DFS and OS in node-positive patients treated with mastectomy, post-mastectomy RT, and taxane-based chemotherapy, although the rate of locoregional recurrence was low. • We evaluated the benefit of IMNI in modern era. • In taxane-based chemotherapy era, locoregional recurrence was very low (5.2%) in node-positive breast cancer. • IMNI was associated with improved survival. [ABSTRACT FROM AUTHOR]

[Display omitted] • HSF directly inhibits IAV attachment and entry into the cells via blockage of hemagglutinin. • HSF represses neuraminidase activity of H1N1 and H3N2 IAV. • HSF protects cells from the cytopathic effect of H1N1 and H3N2 IAV infection. • Quercetin in HSF was identified as an active component of anti-influenza viral activity. Hoveniae Semen Seu Fructus (HSF) is a fruit and seed of Hovenia dulcis Thunb. Here, we first report HSF water extract contains a potent anti-influenza A virus (IAV) effect via inhibition of neuraminidase and hemagglutinin and a direct virus-killing effect. We examined the effect of WHSF on IAV infection using GFP-tagged Influenza A/PR/8/34. FACS analysis and fluorescent microscopy showed a dose-dependent inhibitory effect of WHSF against IAV infection. WHSF also suppressed the cytopathic effects of H1N1 and H3N2 IAV. Immunofluorescence and qPCR analyses confirmed WHSF significantly decreases IAV protein and RNA expressions. Time of addition and plaque assays revealed WHSF affects viral replication in the early stage via modulating hemagglutinin and inducing virucidal effects. Furthermore, WHSF suppressed the neuraminidase activity of H1N1 and H3N2 IAV. Quercetin, not taxifolin in WHSF inhibited IAV infection. Our results suggest WHSF could be developed as a natural antiviral agent to prevent IAV infection. [ABSTRACT FROM AUTHOR]

The role of regional nodal irradiation (RNI) after preoperative systemic treatment (PST) with targeted therapy for HER2-positive breast cancer remains uncertain. This study aimed to investigate the impact of RNI on locoregional recurrence (LRR) and disease-free survival (DFS) outcomes after docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) for PST. We retrospectively analyzed 255 patients who were treated with six cycles of TCHP between 2016 and 2019. The patients were divided into four groups based on clinical nodal involvement: group A, with no nodal disease; group B, with axillary lymph node (AXL) level I; group C, with AXL level I with II/III; and group D, with supraclavicular or internal mammary nodes. The RNI group had more advanced nodal disease (C/D) than the no RNI group (56.9 % vs. 6.8 %). With a median follow-up of 51.3 months, there were two (0.8 %), three (1.2 %), and 15 (5.9 %) local, regional, and distant metastases, respectively. LRR did not differ significantly according to the RNI (2.6 % vs. 1.0 %, p = 0.651). Group D had the most frequent distant metastases (17.5 %; p = 0.005). The 4-year DFS rate was 92.7 %, and DFS did not improve significantly after RNI (p = 0.074). When stratified by clinical nodal groups and pathological axillary response, RNI had no effect on LRR/DFS outcomes. With a rare incidence of LRR, RNI did not significantly affect LRR or DFS in patients with HER2-positive breast cancer after with PST-TCHP. However, intensive systemic treatment is required for advanced diseases (C/D). Selective de-intensified RNI and intensified systemic treatment should be investigated in future studies. • Contrary to the rare occurrence of local (0.8 %) or regional (1.2 %) recurrences, a notable 5.9 % of patients developed distant metastasis in HER2-positive breast cancer treated with preoperative systemic therapy with TCHP. • Regional node irradiation (RNI) did not significantly affect locoregional recurrence or disease-free survival, regardless of clinical/pathological disease status. • Patients with supraclavicular or internal mammary node metastasis require intensive systemic treatment due to the higher risk of distant metastasis. • Implementing selective de-intensified RNI and intensified systemic treatment could improve patient management in HER2-positive breast cancer. [ABSTRACT FROM AUTHOR]

A positive resection margin after breast-conserving surgery (BCS) usually requires re-excision, which impairs cosmetic outcomes and causes considerable distress. This study aimed to evaluate the prognosis of patients with positive resection margin after BCS and the role of radiation therapy (RT) in these patients. We analyzed 297 patients who underwent BCS for breast cancer and had invasive carcinoma or ductal carcinoma in situ (DCIS) within less than 1 mm from the resection margin in Samsung Medical Center from January 2000 to June 2012. The association between RT dose and the incidence rate of ipsilateral breast tumor recurrence (IBTR) was examined. After a median follow-up of 78 months, the incidence rate of IBTR in all patients was 4.6% after 5 years. In the multivariate analysis, the unfavorable factors associated with IBTR were age < 40 years (p = 0.019), RT dose (<60 Gy vs. > 66 Gy, p = 0.012; 60–66 Gy vs. > 66 Gy, p = 0.017), and discontinuation of hormone therapy (p = 0.001). Among the patients with invasive carcinoma or DCIS within less than 1 mm from the resection margin, adjuvant RT with higher dose > 66Gy EQD2 might improve local control. Further prospective studies are warranted to validate the benefit and risk of a high dose boost after BCS in patients with a positive resection margin. • IBTR rate of tumors with margins < 1 mm after BCS was 4.6% at 5-years. • Older age, hormone positivity, and hormone therapy were favorable factors for local control. • RT dose > 66 Gy was associated with lower local recurrence in patients with margins < 1 mm without re-excision. [ABSTRACT FROM AUTHOR]

This multi-institutional study intended to investigate the effect of tumor bed boost in patients who achieved pathologic complete response (ypCR) following neoadjuvant chemotherapy (NAC) and breast-conserving therapy (BCT). We identified 180 patients who initially had lymph node (LN) metastasis and achieved ypCR (ypT0/isN0) following NAC and BCT from the 13 institutions of the Korean Radiation Oncology Group (KROG) 16-16 and KROG 12-05. The effect of tumor bed boost on loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) rates was analyzed. In all patients, five-year LRC, DFS and OS rates were 97.5%, 95.4%, and 99.4%, respectively. Tumor bed boost was performed in 158 (87.8%) patients. Advanced N-stage (cN2-3, p = 0.036), close resection margin (p < 0.001), and sentinel lymph node biopsy (p = 0.040) were unfavorable factors for DFS. Tumor bed boost was not a significant factor for LRC, DFS, and OS. This study suggests the benefit of tumor bed boost might be minimal in ypCR patients following NAC and BCT. Larger prospective studies are needed to address this issue. • Patients who achieved ypCR following neoadjuvant chemotherapy and breast conserving surgery have good prognosis. • Tumor bed boost was not a significant factor for local control and survival in ypCR patients. • The benefit of tumor bed boost in ypCR patient needs to be investigated in further study. [ABSTRACT FROM AUTHOR]

Background: The anti-inflammatory actions of Polygonum cuspidatum, Angelica gigas, Sophora flavescens and Arctium fruit are well known. Nonetheless, effects of herbal combination (PASA) or its fermentation by microorganisms (F-PASA) on the allergic response remain unknown.Purpose: We investigated whether PASA or F-PASA could inhibit IgE/antigen complex (IgE/Ag)-mediated allergic responses.Methods: To evaluate and compare anti-allergic actions of PASA and F-PASA, we performed cell viability, β-hexosaminidase activity, ELISA assays for cytokines and eicosanoids, immunoblot analysis, HPLC analysis and passive cutaneous anaphylaxis (PCA) models.Results: F-PASA had stronger anti-degranulation actions (IC50, 510.9  µg/ml) than PASA (IC50, 1,261  µg/ml) without cytotoxicity until 2000  µg/ml in IgE/Ag-activated RBL-2H3 cells. Additionally, F-PASA inhibited formation of tumor necrosis factor-α (IC50, 147.4  µg/ml), interleukin-4 (IC50, 213.4  µg/ml), prostaglandin D2 (IC50, 42.40  µg/ml) and leukotriene C4 (IC50, 157.9  µg/ml). Moreover, F-PASA dose-dependently inhibited the phosphorylation and expression of proteins that are related to the FcεRI and arachidonate cascades. Consistent with in vitro studies, F-PASA from 25 to 100  mg/kg also suppressed IgE/Ag-induced PCA reaction more than PASA did in mice. In phytochemical analysis, using PASA and F-PASA, F-PASA showed a higher level of emodin-8-O-β-d-glucoside, whereas the level of arctiin, an artigenin glycoside, was reduced compared with that using PASA.Conclusion: These findings indicate that F-PASA, including both artigenin and emodin-8-O-β-d-glucoside, possesses stronger anti-allergic properties. Therefore, F-PASA may be useful as a functional food or as a phytomedicine for allergic diseases. [ABSTRACT FROM AUTHOR]

Abstract Background The objective of this study was to evaluate ipsilateral breast tumor recurrence (IBTR) rates in patients with small (≤1 cm) ductal carcinoma in situ (DCIS) who were followed up for more than 15 years. Methods We identified 209 patients with primary small (≤1 cm) DCIS without invasion who received curative excision with and without adjuvant radiation therapy (RT) from 1996 to 2009. IBTR rates and prognostic factors in all patients were estimated by univariate and multivariate analyses. Results With a median follow-up of 104 months, eight (53.3%) had DCIS recurrence and seven (46.7%) had recurrence of invasive ductal carcinoma. IBTR rate of all patients was 7.5% at 10 years and 12.1% at 15 years. In univariate analysis, age and subtypes were significant factors for IBTR. In multivariate analysis, resection margin, adjuvant RT, and endocrine therapy were significant factors for IBTR. Conclusions IBTR rate of small (≤1 cm) DCIS following excision with or without adjuvant RT was 12.1% at 15 years. Adjuvant RT and endocrine therapy were associated with lower IBTR rate in small DCIS. Highlights • Ipsilateral breast tumor recurrence (IBTR) rate of small (≤1 cm) ductal carcinoma in situ (DCIS) was 12.1% at 15 years. • Adjuvant radiation therapy and endocrine therapy were significant factors for IBTR. • Together with appropriate endocrine therapy, adjuvant RT could lower IBTR in small DCIS. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Lappaol A has anti-allergic effect on IgE/antigen-activated mast cells. • Lappaol A inhibits the activation of arachidonate and FcεRI signaling cascades. • Lappaol A attenuates allergic responses in IgE/antigen-exposed mice. Abstract The biological effect of lappaol A, a lignan, is derived from Arctium lappa , and is relatively unknown; however, lignans have various beneficial properties. Therefore, we investigated the effects of lappaol A on the immunoglobulin E/antigen (IgE/Ag)-mediated allergic response in mast cells and mice. Lappaol A significantly reduced the release of β-hexosaminidase, IL-4, TNF-α, PGD 2 and LTC 4 with IC 50 values of 131.3 μM, 11.58 μM, 59.50 μM, 17.85 μM and 10.99 μM, respectively, in IgE/Ag-activated RBL-2H3 cells. Moreover, lappaol A suppressed the activation of the arachidonate and FcεRI signaling cascades in the cells. Furthermore, lappaol A suppressed the IgE/Ag-mediated passive cutaneous anaphylaxis reaction, ear edema and mast cell infiltration in the ear tissues of IgE/Ag-exposed mice. In conclusion, these findings suggest that lappaol A exhibits anti-allergic activity by inhibiting the activation of the arachidonate and FcεRI signaling cascades in IgE/Ag-activated mast cells. Therefore, this information may help to elucidate the anti-allergic action of lappaol A and Arctium lappa L. [ABSTRACT FROM AUTHOR]

Purpose Information on tubular carcinoma (TC) of breast is limited due to its rarity. A multi-institutional study was performed to investigate the prognosis and failure patterns of TC compared to invasive ductal carcinoma (IDC). Materials and methods We collected retrospective data on 205 patients with TC from eleven institutions. For each TC case, 3 cases with IDC were matched according to similar size, t-stage, and n-stage from the same institution. Patterns of failure, disease free survival (DFS) and overall survival (OS) were assessed and compared between the groups. Results DFS at 5 years was 98.8% and 97.3% and OS at 5 years was 99.5% and 99.6% in TC and IDC, respectively. Among the patients with TC, 5 patients (2.4%) developed contralateral breast cancer, while 3 patients (0.5%) presented with contralateral breast cancer in patients with IDC. Conclusions The TC of breast presents an excellent prognosis, but the contralateral breast cancer tends to be more frequently observed compared to IDC in Korean women. [ABSTRACT FROM AUTHOR]

Agastache rugosa (Fisch. & C.A. Mey.) Kuntze ( A . rugosa ), commonly known as Korean mint, has traditionally been used for both food and medicine, depending on which part of the plant is used. We investigated the anti-proliferative activities of A . rugosa extract in vascular smooth muscle cells (VSMCs) and analysed several molecular pathways to determine the active component of the extract. A . rugosa extract inhibited PDGF-BB-stimulated VSMC proliferation and DNA synthesis. A . rugosa extract caused arrest of the cell cycle at the G 0 /G 1 transition by up-regulating the levels of p21 WAF1/CIP1 and p27 KIP1 . Among the components of the A. rugosa extract reported in a previous study, rosmarinic acid (RA) only inhibited DNA synthesis and dose-dependently suppressed PCNA expression. These results indicate that A . rugosa extract, which includes the active component RA, demonstrates anti-proliferative activity by arresting the cell cycle at the G 0 /G 1 phase through the upregulation of p21 WAF1/CIP1 and p27 Kip1 expression. [ABSTRACT FROM AUTHOR]

Background: Sanguisorba officinalis L. (SOL) is a perennial plant widely distributed in Asia, its roots are well-known as a traditional herbal medicine to treat burns, chronic intestinal infections, scalds, and inflammation in Korea. Also, the roots of SOL are used for treatment of many types of allergic skin diseases, including urticarial, eczema, and allergic dermatitis.Purpose: In this study we investigated the underlying mechanism of anti-inflammatory effect of an ethanol extract of SOL roots (ESOL).Study Design: The ability of ESOL to inhibit inflammatory skin disorder was tested in human keratinocyte HaCaT cells.Methods: Viability test using MTT assay were used to determine non-cytotoxic concentrations of ESOL on HaCaT cells. ESOL-mediated inhibition of the tumor necrosis factor (TNF)-α/interferon (IFN)-γ-induced production of pro-inflammatory chemokines-such as macrophage-derived chemokine (MDC), regulated on activation, normal T-cell expressed and secreted (RANTES), interleukin (IL)-8, and thymus and activation regulated chemokine (TARC)-at the mRNA level was determined by real-time reverse transcription-polymerase chain reaction (RT-PCR). The ability of ESOL to reduce the expression of pro-inflammatory marker proteins was evaluated by Western blot analysis and immunocytochemistry.Results: ESOL reduced the production of MDC, RANTES, IL-8, and TARC in HaCaT cells stimulated with TNF-α/IFN-γ at both protein and mRNA levels. ESOL also suppressed the phosphorylation of signal transducer and activator of transcription (STAT)-1, extracellular signal-regulated kinase (ERK), and inhibited both nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (IκB-α) degradation and the nuclear translocation of NF-κB/p65. ESOL exerts anti-inflammatory effects by suppressing the expression of TNF-α/IFN-γ-stimulated chemokines and pro-inflammatory molecules via a blockade NF-κB, STAT-1, and ERK activation.Conclusion: Our results suggest the preventive potential of ESOL as a herbal medicine for the treatment of inflammatory skin diseases. [ABSTRACT FROM AUTHOR]

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[Display omitted] • Lotus (Nelumbo nucifera Gaertn.) leaf inhibits influenza virus infection. • Lotus leaf directly blocks IAV binding onto the cells. • Lotus leaf suppresses neuraminidase and hemagglutinin of IAV. • Lotus leaf prevents cytopathic effect by H1N1 and H3N2 IAV. • Isoquercitrin in the lotus leaf is the main active component for an anti-IAV efficacy. Lotus (Nelumbo nucifera Gaertn.) is a perennial aquatic plant, that has been used in folk to treat various diseases. Here, we first demonstrate the water extract of lotu s leaf (WLL) has a strong inhibitory effect on influenza A virus (IAV) infection by inhibiting neuraminidase (NA) and hemagglutinin (HA). To investigate the effect of WLL on IAV infection, we used green fluorescent protein (GFP)-tagged Influenza A/PR/8/34, fluorescence-activated cell sorting (FACS) analysis, and plaque reduction assay. WLL significantly repressed viral infection, dose-dependently. Immunofluorescence (IF) analysis confirmed that WLL reduces influenza HA, NA, M2, and NP viral proteins expression. WLL strongly inhibited HA and reduced NA activity of IAV. Among six components in WLL, isoquercitrin exerted potent antiviral efficacy. Additionally, WLL potently inhibited the cytopathic effect caused by H1N1 or H3N2 IAV. In conclusion, our results suggest that WLL could be used as a natural viral inhibitor for H1N1 and H3N2 influenza viral infection. [ABSTRACT FROM AUTHOR]

• Vertebral compression fracture (VCF) may occur after ablative radiotherapy. • Rates and risk factors of VCF were analyzed in patients with spine metastasis. • Twenty-one (12.8%) patients experienced VCF and the 1-year VCF rate was 12.1%. • VCF rates were significantly different by PTV receiving ≥15 Gy (PTV_V 15Gy). • The 1-year rates were 3.8% and 22.1% in PTV_V 15Gy ≤42 and >42 cm3, respectively. This analysis was performed to evaluate the incidence of vertebral compression fracture (VCF) and determine the contributing factors for VCF in patients undergoing single-fraction stereotactic body radiotherapy (SBRT) for spinal bone metastases (SBM). A retrospective review of medical records was conducted for patients undergoing SBRT for SBM at our institution between January 2010 and December 2018. Patients who had undergone neither pre-SBRT surgical excision nor post-SBRT prophylactic fixation were included. The effects of clinical and dosimetric parameters were analyzed with respect to VCF risk. The following dosimietric parameters of the planning target volume (PTV) were calculated: mean/minimum/maximum dose, radiation dose to 10–90% volume, and irradiated volume receiving more than 10–25 Gy (PTV_V 10 – 25 Gy). Among 163 patients (179 vertebrae), 21 (12.8%) experienced VCF. The 1-year and 2-year VCF rates were 12.1% and 13.2%, respectively. Among dosimetric parameters, PTV_V15 Gy was the most significant for VCF prediction. In a univariate analysis, breast or prostate primary, no vertebral body collapse, and PTV_V 15 Gy ≤42 cm3 were significantly associated with a lower incidence rate of VCF. In a multivariate analysis, PTV_V 15 Gy was the only significant factor for VCF risk. The 1-year VCF rate was 3.8% in patients with PTV_V 15 Gy ≤42 cm3, while it was 22.1% in those with PTV_V 15 Gy > 42 cm3 (p < 0.01). SBRT-related VCF was found in 12% of patients in our institution. The PTV_V 15 Gy is a significant factor for VCF prediction. [ABSTRACT FROM AUTHOR]

Abstract: Aim of the study: The root of Angelica gigas Nakai (Korean “Dang-Gui”) has been used to treat female afflictions and anemia in traditional oriental herbal medicine since ancient times in Korea. The objective of this study is to identify the anti-cancer mechanism induced by A. gigas extract including decursin and decursinol angelate in human cervical cancer cells for scientific evidence regarding herbal therapy. Materials and methods: The extract of A. gigas, decursin, and decursinol angelate was used to evaluate the anti-cancer effects on HeLa cells. Cell viability was evaluated by MTT assay and cell cycle regulation was analysed by FACS program. The expression of apoptotic proteins was confirmed by Western blot analysis and proteome profiler array. Results: The extract of A. gigas containing decursin and decursinol angelate exhibited anti-cancer effect on HeLa cells through the significant activation of caspases and the cleavage of PARP. Expression of TRAIL and TRAIL receptors was also increased by two active components of A. gigas, respectively. In particular, two components regulated the expression of apoptosis-related proteins such as Bcl-2, Bcl-x, survivin, cIAP-1, -2, XIAP, etc. Conclusions: These results suggest that TRAIL expression induced by extract of A. gigas stimulates the extrinsic and intrinsic apoptosis pathway by activating caspase-8 and caspase-9, respectively. Thus, extract of A. gigas including decursin and decursinol angelate takes a role in inhibition of cell-proliferation and activation of apoptosis in cervical cancer and could be developed as therapeutic anti-cancer agent against cervical cancer. [Copyright &y& Elsevier]