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Background: Tumor progression following endocrine therapy is considered to indicate resistance to endocrine drugs due to a variety of mechanisms. An insufficient dose of endocrine drugs is one of the causes for treatment failure in some patients with high hormone-receptor (HR)-expressing advanced breast cancer. This study aimed to explore the efficacy of high-dose tamoxifen (TAM) treatment in patients with advanced breast cancer with highly expressed HR. Materials & methods: This was a single-arm, phase II pilot study that enrolled patients with advanced breast cancer with high HR expression (estrogen receptor ⩾60% and/or progesterone receptor ⩾60%) following routine endocrine therapy. All enrolled patients received a high-dose of TAM (100 mg/day) until disease progression. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and safety. Exploratory endpoints included the predictive value of 16α-18F-17β-fluoroestradiol quantitative positron emission tomography/computed tomography (18F-FES PET/CT) for treatment efficacy. Results: A total of 30 patients were enrolled between September 2017 and February 2019. The median PFS was 6 months [95% confidence interval (CI) 4.9–7.1] and the median OS was 15.6 months (95% CI 8.3–22.9). Five patients experienced a partial response (PR) and none experienced a complete response (CR), with an ORR of 16.7% and CBR of 33.3%. No severe adverse events were observed. Lesions with 18F-FES maximum standardized uptake value (SUVmax) ⩾4 had a significantly longer PFS [median 9.2 months, (95% CI 6.9–11.6)] compared with lesions with a 18F-FES SUVmax <4 [median 4.8 months, (95% CI 3.9–5.6); p = 0.022]. Conclusion: A high-dose of TAM is effective and safe for patients with advanced breast cancer with high HR expression. 18F-FES SUVmax values may predict the local clinical benefits of high-dose TAM. Trial Registration: [ClinicalTrials.gov identifier: NCT0304565] [ABSTRACT FROM AUTHOR]

Abstract: Argonaute/Piwi proteins can regulate gene expression via RNA degradation and translational regulation using small RNAs as guides. They also promote the establishment of suppressive epigenetic marks on repeat sequences in diverse organisms. In mice, the nuclear Piwi protein MIWI2 and Piwi‐interacting RNAs (piRNAs) are required for DNA methylation of retrotransposon sequences and some other sequences. However, its underlying molecular mechanisms remain unclear. Here, we show that piRNA‐dependent regions are transcribed at the stage when piRNA‐mediated DNA methylation takes place. MIWI2 specifically interacts with RNAs from these regions. In addition, we generated mice with deletion of a retrotransposon sequence either in a representative piRNA‐dependent region or in a piRNA cluster. Both deleted regions were required for the establishment of DNA methylation of the piRNA‐dependent region, indicating that piRNAs determine the target specificity of MIWI2‐mediated DNA methylation. Our results indicate that MIWI2 affects the chromatin state through base‐pairing between piRNAs and nascent RNAs, as observed in other organisms possessing small RNA‐mediated epigenetic regulation. [ABSTRACT FROM AUTHOR]

Currently, there is an increasing interest in the use of Aloe Vera in the food industry, with it being used as a source of functional foods in drinks, beverages, and ice creams. In addition, there are several reports about the antifungal activity of Aloe Vera on human mycological diseases. However, little evidence exists on the effect of Aloe extracts on fruit postharvest diseases caused by fungi, either ex-vivo or in vitro. In recent years, there have been some reports on the effect of Aloe extracts applied at postharvest in controlling fruit spoilage by fungi. However, no in-depth information has been reported on the role of Aloe extracts in decay development in fruits previously inoculated with fungi responsible for postharvest diseases or defense-related enzyme activities and modulation of antioxidant system activities. Thus, the objective of the present work was to evaluate the protective effects of Aloe extracts on Red Fuji apple fruit decay caused by Botrytis cinerea, as well as the effect of Aloe extracts on the disease resistance ability in Red Fuji apple fruit. In order to search for an alternative to synthetic fungicides for the control of the postharvest decay of Red Fuji apple fruits, the potential of using Aloe extract flavonoid for the control of postharvest gray mold incidence of Red Fuji apple fruits was investigated. Red Fuji apple fruits were disinfected with 75%(v/v) ethanol for 2 min., rinsed with tap water, air-dried, and then divided randomly into four treatment groups, with 140 fruit in each group. Three groups were dipped into 0.020, 0.035 and 0.050 g/mL Aloe extract flavonoid solutions for 5 min. at room temperature (23±1)°C. Another group (the control) was treated with distilled water. A uniform wound (4mm deepx3 mm wide) was made at the equator of each fruit using a sterile dissecting needle, followed by the inoculation of a20 μL conidial suspension of B.cinerea (1×108spores/mL) into each wound site. Inoculated fruit were placed in covered plastic boxes with small holes, and stored at (23±1)°C and RH 85%-90%. The diameters of lesions caused by B.cinerea in the apple fruit were recorded each day after inoculation, and each treatment had three replicates. The remaining fruit with inoculations were used for determination of physio-biochemical parameters. The results showed that Aloe extract flavonoid significantly decreased the incidence of gray mold rot in Red Fuji apple fruits, and effectively suppressed the expansion of lesions in vivo. After four-day storage, the gray mold rot incidence of Red Fuji apple fruits that were treated with the concentration of Aloe extract flavonoid (0.035 g/L, 0.050 mg/L) was 73% and 53% respectively, which was significantly lower than that of the control (93%). Concurrently, Aloe extract flavonoid increased the activity of peroxidase (POD), polyphenol oxidase (PPO), phenylalanine ammonia enzyme (PAL), chitinase (CHT), and β-1,3-glucanase (GLU). Phenolics content also increased significantly. These results indicated that increased disease resistance of Red Fuji apple fruit after Aloe extract flavonoid treatment during storage might be attributed to an elicitation of defense response involving the enhancement of defense-related enzyme activities and the modulation of antioxidant system activities. [ABSTRACT FROM AUTHOR]

Lessons Learned: Studies targeting the androgen receptor (AR) signaling pathway in aromatase inhibitor (AI)‐resistant breast cancer are limited.Bicalutamide, one of the commonly used AR inhibitors in prostate cancer, in combination with AI, did not show synergistic activity in patients with estrogen receptor‐positive and AI‐resistant disease in this phase II, single‐arm study.The clinical benefit rate and objective response rate at 6 months were 16.7% and 0%, respectively, and the study was terminated after the first stage. Background: Endocrine resistance is a major problem in clinical practice. Studies have shown that androgen receptor (AR) signaling activation may be one of the mechanisms, and targeting AR showed some promising results in AR‐positive triple‐negative breast cancer. The aim of this study was to assess the efficacy and safety of bicalutamide plus another aromatase inhibitor in patients with nonsteroidal aromatase inhibitor (AI) or steroidal AI resistance and estrogen receptor (ER)‐positive and AR‐positive advanced breast cancer. Methods: A Simon's two‐stage, phase II, single‐arm study was conducted. We assumed the clinical benefit rate (CBR) of 40% would be significant in clinical practice. In this case, if ≥4 patients of the 19 patients in the first stage benefited from treatment, the CBR would achieve the assumed endpoint. If fewer than four patients benefited from treatment in the first stage, the trial would be terminated. All patients received bicalutamide 50 mg per day orally plus another aromatase inhibitor. The primary outcome was CBR; secondary outcomes included objective response rate (ORR), progression‐free survival (PFS), and tolerability. Results: A total of 19 patients enrolled in the first stage, and 18 patients met all criteria for analysis. The trial terminated according to protocol after the first stage. After a median follow‐up of 14 months, the CBR at 6 months was 16.7% (3/18); no patients with partial or complete response were observed. The median PFS was 2.7 months. Bicalutamide in combination with AI was well tolerated. Conclusion: Bicalutamide in combination with another AI did not show synergistic activity in patients with ER‐positive breast cancer and AI resistance. Results suggest that no more large‐sample clinical trials should be conducted in this population for overcoming endocrine resistance. [ABSTRACT FROM AUTHOR]

Introduction: The Center for Medicare and Medicaid Services introduced an End-Stage Renal Disease Prospective Payment System (PPS) in 2011 to increase the utilization of home dialysis modalities, including peritoneal dialysis (PD). Several studies have shown a significant increase in PD utilization after PPS implementation. However, its impact on patients with kidney allograft failure remains unknown., Methods: We conducted an interrupted time series analysis using data from the US Renal Data System (USRDS) that include all adult kidney transplant recipients with allograft failure who started dialysis between 2005 and 2019. We compared the PD utilization in the pre-PPS period (2005-2010) to the fully implemented post-PPS period (2014-2019) for early (within 90 days) and late (91-365 days) PD experience., Results: A total of 27,507 adult recipients with allograft failure started dialysis during the study period. There was no difference in early PD utilization between the pre-PPS and the post-PPS period in either immediate change (0.3% increase; 95% CI: -1.95%, 2.54%; p = 0.79) or rate of change over time (0.28% increase per year; 95% CI: -0.16%, 0.72%; p = 0.18). Subgroup analyses revealed a trend toward higher PD utilization post-PPS in for-profit and large-volume dialysis units. There was a significant increase in PD utilization in the post-PPS period in units with low PD experience in the pre-PPS period. Similar findings were seen for the late PD experience., Conclusion: PPS did not significantly increase the overall utilization of PD in patients initiating dialysis after allograft failure., (© 2024 S. Karger AG, Basel.)

Background: Atrial fibrillation (AF), which occurs four to six times more frequently in hypertrophic cardiomyopathy (HCM) patients than in the general population, is the most common persistent arrhythmia and has a substantial therapeutic consequence. In HCM patients, there are currently no discovered signs that could be utilized to identify AF., Methods: From 2018 to 2022, 493 individuals with a continuous diagnosis of HCM were examined at Beijing Anzhen Hospital. AF was proven using routine electrocardiography (ECG), 24-hour Holter ECGs, or bedside ECGs. Echocardiography and blood tests were performed for all patients. Analysis and comparison of the traits were performed in HCM patients with AF (n = 77) and without AF (n = 416)., Results: Age ( p < 0.001), prevalence of ventricular tachycardia (VT, p < 0.001), prevalence of pulmonary artery hypertension ( p = 0.027), and albumin-to-globulin ratio (AGR, p = 0.046) were all significantly higher in patients with AF, compared to patients without AF. In multivariate logistic analysis, age (odds ratio [OR], 1.063; 95% confidence interval [CI], 1.032-1.095; p < 0.001), history of VT (OR, 2.702; 95% CI, 1.007-7.255; p = 0.048), AGR (OR, 3.477; 95% CI, 1.417-8.536; p = 0.007), left atrial diameter (OR, 1.132; 95% CI, 1.073-1.194; p < 0.001), left ventricular end-diastolic diameter (OR, 0.861; 95% CI, 0.762-0.974; p = 0.017), left ventricular end-systolic diameter (OR, 1.239; 95% CI, 1.083-1.417; p = 0.002), and peak A wave velocity (OR, 0.983; 95% CI, 0.972-0.994; p = 0.002) were independently associated with AF in HCM patients. In the receiver operating characteristic curve analysis, the area under the curve for the established model was 0.819 (95% CI, 0.755-0.883, p = 0.033), with a sensitivity and specificity of 0.763 and 0.816, respectively, for AF occurrence in HCM patients., Conclusions: In individuals with HCM, a history of VT and a higher AGR are independently linked to AF. Further investigation is necessary to determine whether increased AGR represents a risk factor for embolic stroke or cardiovascular death., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Objective: To develop and validate a hybrid model incorporating CT-fractional flow reserve (CT-FFR), pericoronary fat attenuation index (pFAI), and radiomics signatures for predicting progression of white matter hyperintensity (WMH)., Methods: A total of 226 patients who received coronary computer tomography angiography (CCTA) and brain magnetic resonance imaging from two hospitals were divided into a training set ( n  = 116), an internal validation set ( n  = 30), and an external validation set ( n  = 80). Patients who experienced progression of WMH were identified from subsequent MRI results. We calculated CT-FFR and pFAI from CCTA images using semi-automated software, and segmented the pericoronary adipose tissue (PCAT) and myocardial ROI. A total of 1,073 features were extracted from each ROI, and were then refined by Elastic Net Regression. Firstly, different machine learning algorithms (Logistic Regression [LR], Support Vector Machine [SVM], Random Forest [RF], k-nearest neighbor [KNN] and eXtreme Gradient Gradient Boosting Machine [XGBoost]) were used to evaluate the effectiveness of radiomics signatures for predicting WMH progression. Then, the optimal machine learning algorithm was used to compare the predictive performance of individual and hybrid models based on independent risk factors of WMH progression. Receiver operating characteristic (ROC) curve analysis, calibration and decision curve analysis were used to evaluate predictive performance and clinical value of the different models., Results: CT-FFR, pFAI, and radiomics signatures were independent predictors of WMH progression. Based on the machine learning algorithms, the PCAT signatures led to slightly better predictions than the myocardial signatures and showed the highest AUC value in the XGBoost algorithm for predicting WMH progression (AUC: 0.731 [95% CI: 0.603-0.838] vs.0.711 [95% CI: 0.584-0.822]). In addition, pFAI provided better predictions than CT-FFR (AUC: 0.762 [95% CI: 0.651-0.863] vs. 0.682 [95% CI: 0.547-0.799]). A hybrid model that combined CT-FFR, pFAI, and two radiomics signatures provided the best predictions of WMH progression [AUC: 0.893 (95%CI: 0.815-0.956)]., Conclusion: pFAI was more effective than CT-FFR, and PCAT signatures were more effective than myocardial signatures in predicting WMH progression. A hybrid model that combines pFAI, CT-FFR, and two radiomics signatures has potential use for identifying WMH progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Hou, Jin, Zhang, Xu, Cui, Qin, Han, Yuan, Zheng, Peng, Shu and Gong.)

Background: Attributed to inter-tumor heterogeneity, the therapeutic effect of salvage treatment is diverse and different malignant lesions might manifest various therapeutic responses among advanced breast cancer (ABC) patients. The present study aimed to explore the influence of the mode of lesion response on the subsequent treatment and to subclassify ABC patients for precise prognosis prediction., Methods: Based on the inclusion and exclusion criteria, ABC patients were retrospectively collected and followed up in the Guangdong Provincial Hospital of Chinese Medicine between 2018 and 2021. The treatment responses of all malignant lesions were evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Testing subclassified models were constructed based on different assembly mode of progressed malignant lesions for further classification of ABC patients experiencing disease progression following first-line treatment. Multivariate survival analyses were performed to assess the second-line progression-free survival (PFS) of various subgroups and screen the suitable classification model. The most suitable model was utilized to classify enrolled ABC patients as a heterogeneous progression-disease (Heter-PD) group or homogeneous progression-disease (Hom-PD) group. Univariate analysis and multivariate Cox regression survival analyses were performed to assess the prognostic value of each variable., Results: A total of 70 ABC patients experiencing disease progression after first-line treatment were enrolled into the analyses and underwent median follow-up of 10.36 months. We constructed 3 testing models and Model C (Hom-PD was defined when all the target and non-target lesions were evaluated as progression, with or without new lesions) could further distinguish ABC patients with worse survival. The second-line progression-free survival (PFS) times were significantly different between two groups (11.04 vs . 6.07 months, P=0.034). For ABC patients retaining partial medication after disease progression of first-line treatment, the Heter-PD group showed a tendency of better second-line PFS than the Hom-PD group (13.18 vs . 3.61 months, P=0.430)., Conclusions: Based on the disease progression mode after first-line treatment, the classification model could classify ABC patients as Hom-PD and Heter-PD subgroups, which manifest distinct prognoses during the sequential treatment. For Heter-PD patients, retainment of partial medication might be a rational choice for second-line therapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-1618/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Taxane-induced peripheral neuropathy (TIPN) is a dose-limiting adverse effect. Ganglioside-monosialic acid (GM1) functions as a neuroprotective factor. We assessed the effects of GM1 on the prevention of TIPN in breast cancer patients., Methods: We conducted a randomized, double-blind, placebo-controlled trial including 206 patients with early-stage breast cancer planning to receive taxane-based adjuvant chemotherapy with a follow-up of more than 1 year. Subjects were randomly assigned to receive GM1 (80 mg, day -1 to day 2) or placebo. The primary endpoint was the Functional Assessment of Cancer Treatment Neurotoxicity subscale score after four cycles of chemotherapy. Secondary endpoints included neurotoxicity evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and the Eastern Cooperative Oncology Group neuropathy scale. All statistical tests were two-sided., Results: In 183 evaluable patients, the GM1 group reported better mean Functional Assessment of Cancer Treatment Neurotoxicity subscale scores than patients in the placebo group after four cycles of chemotherapy (43.27, 95% confidence interval [CI] = 43.05 to 43.49 vs 34.34, 95% CI = 33.78 to 34.89; mean difference = 8.96, 95% CI = 8.38 to 9.54, P < .001). Grade 1 or higher peripheral neurotoxicity in Common Terminology Criteria for Adverse Events v4.0 scale was statistically significantly lower in the GM1 group (14.3% vs 100.0%, P < .001). Additionally, the GM1 group had a statistically significantly lower incidence of grade 1 or higher neurotoxicity assessed by Eastern Cooperative Oncology Group neuropathy scale sensory neuropathy (26.4% vs 97.8%, P < .001) and motor neuropathy subscales (20.9% vs 81.5%, P < .001)., Conclusions: The treatment with GM1 resulted in a reduction in the severity and incidence of TIPN after four cycles of taxane-containing chemotherapy in patients with breast cancer., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: The aim of this study was to assess the prognostic value of lymph node ratio (LNR) in premenopausal patients with luminal breast carcinoma., Materials and Methods: A total of 885 female patients who presented with axillary lymph node-positive luminal breast cancer between 2000 and 2009 were investigated. Using X-tile, we classified patients into low-, intermediate- and high-risk groups based on LNR. The Kaplan-Meier method was used to determine cumulative survival curves. Cox proportional hazards analyses were used to identify the factors that contributed to disease-free (DFS) and overall (OS) survival., Results: The median age of patients was 42 years (range=21-58 years). A training set of 295 patients and a validation set of 590 patients were used to determine the optimal LNR cut-off points (0.20 and 0.63). DFS was 87.7%, 77.4% and 53.9% (p<0.001) and OS was 91.5%, 76.7% and 50.9% (p<0.0001) for the low- (≤0.20), intermediate- (0.21-0.63) and high-risk (>0.63) groups, respectively. The 10-year DFS and OS rates were significantly longer in the low-risk group than in the high-risk group. Nomogram analysis demonstrated that LNR contributed more compared to nodal stage in predicting both DFS and OS., Conclusion: We conclude that LNR strongly predicts prognosis in premenopausal patients with lymph node-positive luminal breast cancer., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The efficacy of trastuzumab in Chinese breast cancer (BC) patients has rarely been reported. This study was designed to compare the clinical outcomes of HER2-positive BC patients receiving or not receiving trastuzumab treatment and HER2-negative BC patients., Patients and Methods: This study involved three groups of patients. The first group was 115 human epidermal growth factor receptor 2 (HER2)-positive BC patients treated with trastuzumab who were enrolled at Sun Yat-sen University Cancer Center between January 2002 and July 2010; the second group was a matched control group of 115 HER2-positive patients who did not receive trastuzumab treatment; the third group was a matched group of 115 HER2-negative patients who received conventional therapy in the adjuvant setting. The primary endpoint was 3-year and 5-year disease-free survival (3-DFS and 5-DFS, respectively). The Kaplan-Meier method, log-rank test, and multivariate Cox proportional hazard regression model were used for survival analysis. The differences in survival rates among the three groups were also analyzed according to two different periods: 2002-2006 and 2007-2010., Results: The median duration of follow-up was 36 months (range, 12-111 months). The 3-DFS rates in the HER2-negative group, the HER2-positive group who received trastuzumab treatment, and the HER2-positive group who did not receive trastuzumab treatment were 82.6%, 89.6%, and 67.0%, respectively. The 3-DFS rate for the total study population was statistically significant (P < 0.001). Further analysis indicated a statistically significant difference in 3-DFS between either of the first two groups and the third group (P < 0.01), but the difference between the first two groups was not statistically significant (P = 0.157). Among the three groups, the 3-DFS rates during 2002-2006 did not have a significant difference compared with that during 2007-2010., Conclusion: This study has further confirmed the efficacy of trastuzumab for HER2-positive operable BC in Chinese patients. It has also demonstrated that the 3-DFS and 5-DFS rates between HER2-positive patients receiving trastuzumab treatment and HER2-negative patients are comparable.