Patterns of de novo metastasis and survival outcomes by age in breast cancer patients: a SEER population-based study.

Background: The role of age in metastatic disease, including breast cancer, remains obscure. This study was conducted to determine the role of age in patients with de novo metastatic breast cancer. Methods: Breast cancer patients diagnosed with distant metastases between 2010 and 2019 were retrieved from the Surveillance, Epidemiology, and End Results database. Comparisons were performed between young (aged ≤ 40 years), middle-aged (41-60 years), older (61-80 years), and the oldest old (> 80 years) patients. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using multivariate Cox proportional hazard models. Survival analysis was performed by the Kaplan-Meier method. Results: This study included 24155 (4.4% of all patients) de novo metastatic breast cancer patients. The number of young, middle-aged, older, and the oldest old patients were 195 (8.3%), 9397 (38.9%), 10224 (42.3%), and 2539 (10.5%), respectively. The 5-year OS rate was highest in the young (42.1%), followed by middle-aged (34.8%), older (28.3%), and the oldest old patients (11.8%). Multivariable Cox regression analysis showed that middle-aged (aHR, 1.18; 95% CI, 1.10-1.27), older (aHR, 1.42; 95% CI, 1.32-1.52), and the oldest old patients (aHR, 2.15; 95% CI, 1.98-2.33) had worse OS than young patients. Consistently, middle-aged (aHR, 1.16; 95% CI, 1.08-1.25), older (aHR, 1.32; 95% CI, 1.23-1.43), and the oldest old patients (aHR, 1.86; 95% CI, 1.71-2.03) had worse BCSS than young patients. Conclusion: This study provided clear evidence that de novo metastatic breast cancer had an age-specific pattern. Age was an independent risk factor for mortality in patients with de novo metastatic breast cancer.

Adherence to post-surgery follow-up assessment and its association with sociodemographic and disease characteristics in patients with breast cancer in Central China.

BACKGROUND: Follow-up after curative surgery is increasingly recognized as an important component of breast cancer care. Although current guideline regulates the follow-ups, there are no relevant studies on the adherence to it in China. This study investigated the post-surgery follow-up and explored its association with patients, tumor and treatment characteristics. METHODS: A total of 711 patients underwent surgical treatment in Shanxi Bethune Hospital from March 2012 to May 2018 were included in this study. Baseline sociodemographic, tumor, and treatment characteristics were obtained from the hospital electronic medical records. The post-surgery follow-up was reviewed and assessed from the patient's follow-up examination record. Factors associated with the first three-year follow up was evaluated using logistic regression analysis. RESULTS: The annual follow-up rate after surgery decreased gradually from 67.1% at the 1st year, 60.2% at the 3rd year to 51.9% at the 4th year, and 43.5% at the 5th year. Loss of follow-up during the first 3 years after surgery was significantly associated with older age (> 65 years), lower medical insurance coverage, axillary lymph node dissection, and less intensity of systemic treatment. CONCLUSION: A significant downtrend of annual follow-up rate for breast cancer survivors was confirmed in this study. Loss of follow-up within the first 3 years after surgery was associated with both patient's characteristics and treatment. These results will provide evidence to help clinicians to develop tailored patient management after curative surgery.

Financial toxicity and its associated patient and cancer factors among women with breast cancer: a single-center analysis of low-middle income region in China.

PURPOSE: To assess the financial toxicity (FT) and to investigate patients and cancer characteristic that associated with it in patients admitted in a tertiary hospital in central China. METHODS: This was a cross-sectional study of 166 patients from 188 with stage 0-III women breast cancer admitted in Bethune hospital in Taiyuan, Shanxi province during January-May 2019. FT was self-reported using of financial Toxicity Comprehensive Rating Scale (COST-FACIT). Patients' sociodemographic factors, clinical examination, and cancer treatment were collected from questionnaire and hospital record. The financial concern and coping strategy was self-reported. Factors associated with FT were identified using linear regression analysis. RESULTS: Of the 166 completed the survey, the COST score ranged 0-40 with a mean of 21.2 (median 22.5, standard deviation 8.1). On multivariate linear regression analysis, older age (ß coefficient: 0.20, 95% CI 0.11-0.29, p < 0.001), higher household income (ß coefficient: 3000-5000 Yuan: 7.88, 95% CI 4.74-11.01, p < 0.001; ≥ 5000 Yuan: 12.81, 95% CI 9.54-16.08, p < 0.001) were positively associated with COST scores. Advanced cancer stage was the strongest predictor of FT among the cancer characteristics (ß coefficient: - 4.52, 95% CI - 7.13-1.92, p = 0.001). To cope with the FT, 131 (78.8%) patients decreased non-medical expenses, and 56 (33.7%) reduced or quitted treatment. CONCLUSIONS: FT was significantly associated with patient's age, income, and cancer stage. Women having financial concerns after diagnosis were more likely to reduce their non-medical expenses and even quit treatments. Clinicians should take into account the FT levels in all patients and work out appropriate treatment strategies for optimal clinical outcome.

Artemisinin analogue SM934 ameliorates the proteinuria and renal fibrosis in rat experimental membranous nephropathy.

AIM: SM934 is a novel water-soluble artemisinin derivative with immunoregulatory activities that has been used to treat murine lupus nephritis. In the current study, we investigated the effects of SM934 on rat experimental membranous nephropathy. METHODS: Passive Heymann nephritis (PHN) was induced in SD rats by intraperitoneal injection of anti-Fx1A serum. The rats were orally administered SM934 (12.5 and 25 mg·kg(-1)·d(-1)) or prednisolone (5 mg·kg(-1)·d(-1)) for 28 d. Blood and urine sample, and kidney tissue were collected for analyses. Human complement C3a-induced injury of HK-2 cells was used for in vitro experiments. RESULTS: Treatment of PHN rats with SM934 or prednisolone attenuated the progression of glomerulonephritis and renal fibrosis, as evidenced by the reduced level of proteinuria and circulating antibodies, as well as by the reduced immune complex deposition, reversed podocyte injuries, and attenuated tubulointerstitial fibrosis in the kidneys. Furthermore, the two drugs suppressed TGF-ß1 expression and Smad2/3 phosphorylation, and increased Smad7 expression in the kidneys. The two doses of SM934 produced almost identical therapeutic effects on PHN rats. Pretreatment with SM934 or a C3a receptor antagonist blocked the C3a-induced epithelial-mesenchymal transition in HK-2 cells in vitro. CONCLUSION: SM934 ameliorates kidney injury and attenuates the tubulointerstitial fibrosis in PHN rats by down-regulation of the TGF-ß1/Smad signaling pathway.

Discovering novel anti-HCV compounds with inhibitory activities toward HCV NS3/4A protease.

AIM: To discover novel hepatitis C virus (HCV) inhibitors and elucidate the mechanism of action of the active compounds. METHODS: HCV subgenomic replicon-based luciferase reporter cell line was used to screen 1200 synthetic compounds with novel structures. Huh7.5.1 cell line stably transfected with HCV NS3/4A protease reporter was established to investigate the anti-HCV mechanism of the active compounds. The active compounds were further examined in an in vitro HCV infection assay to confirm their anti-HCV activity. RESULTS: After two-round screening in the anti-HCV replicon assay, some 2,4-diaminoquinazoline derivatives and carboxamide analogues were found to possess anti-HCV replicon activities (the IC50 values were less than 5 µmol/L). Among them, two representative compounds HZ-1157 and LZ-110618-6 inhibited HCV NS3/4A protease with IC50 values of 1.0 and 0.68 µmol/L, respectively. Furthermore, HZ-1157 and LZ-110618-6 inhibited HCV infection in vitro with IC50 values of 0.82 and 0.11 µmol/L, respectively. CONCLUSION: Some 2,4-diaminoquinazoline derivatives and carboxamide analogues have been identified as novel anti-HCV compounds.

Benzimidazole derivative, BM601, a novel inhibitor of hepatitis B virus and HBsAg secretion.

Hepatitis B virus (HBV) belongs to the Hepadnaviridae family. HBsAg, greatly outnumbered mature virion, has been mysterious since the discovery of HBV. A novel benzimidazole derivative, BM601, is identified inhibiting the secretion of HBV virions and HBsAg, with 50% effective concentration of 0.6µM and 1.5µM, as well as 50% cytotoxicity concentration of 24.5µM. It has no effect on transcription, protein production, nucleocapsid formation or intracellular HBV DNA synthesis. Immunofluorescence analysis suggests that BM601 might inhibit virion and HBsAg secretion by interfering surface protein aggregation in trans Golgi apparatus. Furthermore, BM601 does not trigger cellular stress response or affect HBeAg or host protein secretion. We hypothesize that BM601 is a secretion inhibitor functioning at the level of virion and HBsAg secretion pathway.