BackgroundWomen undergoing chemotherapy for the treatment of breast cancer have frequently reported unmet supportive care needs. Moreover, easily accessible and innovative support is lacking.ObjectiveThe purpose of this trial was to determine the effectiveness of an app-based breast cancer e-support program to address women’s self-efficacy (primary outcome), social support, symptom distress, quality of life, anxiety, and depression. Secondary objectives included exploring the association between women’s health outcomes and the breast cancer e-support usage data.MethodsA multicenter, single-blinded, randomized controlled trial was conducted. A total of 114 women with breast cancer, who were commencing chemotherapy and were able to access internet through a mobile phone, were recruited in the clinics from 2 university-affiliated hospitals in China. Women were randomized either to the intervention group (n=57) receiving breast cancer e-support plus care as usual or the control group (n=57) receiving care as usual alone. The health care team and research assistants collecting data were blinded to the women’s group allocation. Bandura’s self-efficacy theory and the social exchange theory guided the development of the breast cancer e-support program, which has 4 components: (1) a Learning forum, (2) a Discussion forum, (3) an Ask-the-Expert forum, and (4) a Personal Stories forum. Moderated by an experienced health care professional, the breast cancer e-support program supported women for 12 weeks covering 4 cycles of chemotherapy. Health outcomes were self-assessed through paper questionnaires in clinics at baseline before randomization (T0), after 3 (T1), and 6 months (T2) of follow-ups.ResultsFifty-five participants in the intervention group and 49 in the control group completed the follow-up assessments (response rate: 91.2%). During the 12-week intervention, the log-in frequency ranged from 0 to 774 times (mean 54.7; SD 131.4; median 11; interquartile range, IQR 5-27), and the total usage duration ranged from 0 to 9371 min (mean 1072.3; SD 2359.5; median 100; IQR 27-279). Repeated measures multivariate analysis of covariance (intention-to-treat) found that breast cancer e-support + care as usual participants had significant better health outcomes at 3 months regarding self-efficacy (21.05; 95% CI 1.87-40.22; P=.03; d=0.53), symptom interference (−0.73; 95% CI −1.35 to −.11; P=.02; d=−0.51), and quality of life (6.64; 95% CI 0.77-12.50; P=.03, d=0.46) but not regarding social support, symptom severity, anxiety, and depression compared with care as usual participants. These beneficial effects were not sustained at 6 months. Spearman rank-order correlation showed that the breast cancer e-support usage duration was positively correlated with self-efficacy (r=.290, P=.03), social support (r=.320, P=.02), and quality of life (r=.273, P=.04) at 3 months.ConclusionsThe breast cancer e-support program demonstrated its potential as an effective and easily accessible intervention to promote women’s self-efficacy, symptom int...

Hippocampal neuron death is a key factor in vascular dementia (VD) induced by chronic cerebral hypoperfusion (CCH). Dl-3-n-butylphthalide (NBP) is a multiple-effects drug. Therefore, the potential molecular mechanisms underlying CCH and its feasible treatment should be investigated. This study had two main purposes: first, to identify a potential biomarker in a rat model of CCH induced VD using antibody microarrays; and second, to explore the neuroprotective role of NBP at targeting the potential biomarker. Glial cell line-derived neurotrophic factor (GDNF)/GDNF family receptor alpha-1 (GFRα1)/receptor tyrosine kinase (Ret) signaling is altered in the hippocampus of CCH rats; however, NBP treatment improved cognitive function, protected against hippocampal neuron apoptosis via regulation of GDNF/GFRα1/Ret, and activated the phosphorylation AKT (p-AKT) and ERK1/2 (p-ERK1/2) signaling. We also found that 1 h oxygen-glucose deprivation (OGD) followed by 48 h reperfusion (R) in cultured hippocampal neurons led to downregulation of GDNF/GFRα1/Ret. NBP upregulated the signaling and increased neuronal survival. Ret inhibitor (NVP-AST487) inhibits Ret and downstream effectors, including p-AKT and p-ERK1/2. Additionally, both GDNF and GFRα1 expression are markedly inhibited in hippocampal neurons by coincubation with NVP-AST487, particularly under conditions of OGD/R. GDNF/GFRα1/Ret signaling and neuronal viability can be maintained by NBP, which activates p-AKT and p-ERK1/2, increases expression of Bcl-2, and decreases expression of Bax and cleaved caspase-3. The current study showed that GDNF/GFRα1/Ret signaling plays an essential role in the CCH induced VD. NBP was protective against hippocampal neuron apoptosis, and this was associated with regulation of GDNF/GFRα1/Ret and AKT/ERK1/2 signaling pathways, thus reducing cognitive impairment.

Bladder cancer (BCa) threatens human health due to the high occurrence and mortality. Nowadays, more and more researchers focussed on the molecular mechanisms and biological functions of miRNAs in human cancers. The present study aims to study the biological role of miR-454-3p and miR-374b-5p in BCa. The expression levels of miR-454-3p and miR-374b-5p were detected in BCa tissues and cell lines by qRT-PCR analysis. Kaplan–Meier analysis revealed that the expression levels of miR-454-3p and miR-374b-5p were positively correlated with the overall survival (OS) rate of BCa patients. Gain-of-function assays were conducted to demonstrate the inhibitory effects of miR-454-3p and miR-374b-5p on the invasion, migration, and epithelial–mesenchymal transition (EMT) of BCa cells. Mechanically, ZEB2 was found to be a target of both miR-454-3p and miR-374b-5p. Rescue assays revealed that ZEB2 reversed the inhibitory effects of miR-454-3p and miR-374b-5p on the invasion and migration of BCa cell lines. In summary, miR-454-3p and miR-374b-5p negatively regulated invasion and migration of BCa cell lines via targetting ZEB2.

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Nobiletin is a polymethoxy flavonoid isolated from Citrus depressa and Citrus reticulata. It has been reported that nobiletin can suppress tumors. We primarily explored the antitumor effects of nobiletin and the associated potential mechanisms in ACHN and Caki-2 renal carcinoma cells. A CCK-8 assay and cloning experiments were used to assess cell viability, and a transwell assay and scratch test were used to assess metastatic ability. The cell cycle was analyzed by flow cytometry, whereas apoptosis was analyzed using flow cytometry and a terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. Protein expression was examined by Western blot and immunofluorescence. Renal cancer cells were subcutaneously transplanted into nude mice for in vivo studies. The data showed that nobiletin administration significantly dose-and time-dependently suppressed renal cancer cell proliferation; moreover, nobiletin treatment induced cell cycle arrest in the G0/G1 phase and promoted apoptosis. Immunofluorescence analysis indicated that nobiletin decreased the nuclear localization of signal transducer and activator of transcription 3 (STAT3) and YY1-associated protein 1 (YY1AP1). Western blot showed that the levels of phosphorylated SRC, phosphorylated AKT serine/threonine kinase (AKT), and phosphorylated STAT3 were decreased, whereas that of phosphorylated YY1AP1 was increased. The results further showed that application of insulin-like growth factor 1 (IGF1) was able to reverse the nobiletin-induced changes in the levels of phosphorylated AKT, phosphorylated STAT3, and phosphorylated YY1AP1, and could also reverse the antitumor effects of nobiletin. The results of in vivo experiments showed that, compared to the control, tumor volume and weight were both reduced following nobiletin treatment. In conclusion, our study demonstrated that nobiletin can inhibit renal carcinoma cell viability and provides a novel therapeutic approach for the treatment of kidney cancer.

In the present study, the effects of exopolysaccharides (EPS) from nine Lactobacillus strains with a high degree of bio-activity on human colon cancer cell line HT-29 were studied. The extracellular polymeric substances from 4 strains, namely K11, M5, SB27 and ×12, displayed desirable anti-proliferative activity against HT-29 cells. Crude and acidic EPS were purified from the 4 strains and the inhibitory effects were further investigated. The crude and acidic EPS from these 4 strains exerted anti-proliferation effects on HT-29 cells in a dose-dependent manner but were nontoxic to Vero cells. Treatment with EPS significantly induced G0/G1 cell cycle arrest and apoptosis of HT-29 cells. Hoechst 33258 staining of acidic EPS-treated HT-29 cells revealed different degrees of morphological changes within the nucleus and the formation of apoptotic bodies. Caspase-3 activity was markedly upregulated in HT-29 cells following treatment with acidic EPS. In addition, acidic EPS from the SB27 strain demonstrated the most robust inhibitory effect on HT-29 cells. The results of the present study suggest that as an inducer of apoptosis EPS has the potential to be applied in the treatment of colorectal cancer.

Controversies exist between the previous two prognostic nomograms for patients with bone metastatic prostate cancer (PCa), and a nomogram applied to western patients has yet to be established. Thus, we aimed to build a reliable and generic nomogram to individualize prognosis.The independent prognostic factors were identified in a retrospective study of 1556 patients with bone metastatic PCa registered in the Surveillance, Epidemiology and End Results (SEER) database. Besides, the prognostic nomogram was developed using R software according to the result of multivariable Cox regression analysis. Then, the discriminative ability of the nomogram was assessed by analyses of receiver operating characteristic curves (ROC curves). We also performed 1-, 2-, and 3-year calibrations of the nomogram by comparing the predicted survival to the observed survival. Furthermore, the model was externally validated using the data of 711 patients diagnosed at different times enrolled in the SEER database.Age ≥70 years, Gleason score ≥8, PSA value of 201 to 900 ng/ml, stage T4, stage N1, with liver metastases, and Asian/Pacific ethnicity were identified as independent prognostic factors. In the primary cohort, 1-, 2-, and 3-year area under the ROC curve (AUC) of the nomogram for predicting cancer-specific survival (CSS) were 0.71, 0.70, and 0.70, respectively. Besides 1-, 2-, and 3-year AUC were 0.70, 0.68, and 0.69, respectively, in the external validation cohort. Moreover, calibration curves presented perfect agreements between the nomogram-predicted and actual 1-, 2-, and 3-year CSS rate in both the primary and external validation cohorts. In other words, our nomogram has great predictive accuracy and reliability in predicting 1-, 2-, and 3-year CSS for patients with bone metastatic prostate cancer.This study established and validated a prognostic nomogram applied to not only Asian patients but western patients with bone metastatic PCa, which will be useful for patients’ counseling and clinical trial designing.