Randomized controlled trial of mindfulness-based stress reduction (MBSR) on posttraumatic growth of Chinese breast cancer survivors.

Breast cancer (BC) patients in China suffered from a variety of psychology stress such as perceived stress and anxiety, posttraumatic growth (PTG) as a positive factor could promote their psychology health and quality of life. This study aimed to investigate the efficacy of mindfulness-based stress reduction (MBSR) on promoting PTG, decreasing perceived stress and anxiety of Chinese BC patients. A randomized controlled trial of 60 BC patients (Stages I-III) was conducted. They were randomly divided to the 8-week MBSR group or usual care (UC) group. PTG inventory, Perceived Stress Scale of Chinese version (CPSS) and State Trait Anxiety Inventory (STAI) evaluated the PTG level, perceived stress and anxiety at three times(before intervention-T1, after intervention-T2 and follow up at 3 months-T3). A repeated-measures analysis of variance model was used to compare each outcome measure of two groups at the three times. There was one patient discontinued the intervention and one lose to follow up in MBSR group, finally 58 BC patients completed the research. There was no difference between two groups before the intervention. The results showed significant improvements in MBSR group comparing with the UC group that PTG level was much higher after the 8-week intervention and the follow up (F = 34.73, p < .00). At the same time, CPSS (F = 14.41, p < .00) and STAI (F = 15.24, p < .00) scores were significant decreased at T2 and T3. The results showed that MBSR promoted the level of PTG and decreased perceived stress and anxiety state of Chinese BC patients, and the results persisted at three months after intervention. The research preliminary proved that MBSR was suitable to Chinese BC patients. MBSR should be recommending to BC survivors in China.

An antihypertensive drug-AT1 inhibitor attenuated BRCA development promoted by chronic psychological stress via Ang II/PARP1/FN1 pathway.

Chronic psychological stress contributes to the occurrence of cancer and activates the renin-angiotensin system (RAS). However, the mechanisms by which RAS promotes the progression of breast cancer (BRCA) under chronic psychological stress are remain unknown. In this study, we observed elevated levels of Angiotensin II (Ang II) in both serum and BRCA tissue under chronic stress, leading to accelerated BRCA growth in a mouse model. An antihypertensive drug, candesartan (an AT1 inhibitor), effectively attenuated Ang II-induced cell proliferation and metastasis. Utilizing mass spectrometry and weighted gene co-expression network analysis (WGCNA), we identified fibronectin 1 (FN1) as the hub protein involved in chronic stress-Ang II/AT1 axis. Focal adhesion pathway was identified as a downstream signaling pathway activated during the progression of chronic stress. Depletion of FN1 significantly attenuated Ang II-induced proliferation and metastasis of BRCA cells. Poly (ADP-ribose) polymerase 1 (PARP1) was found to bind to the DNA promoter of FN1, leading to the transcription of FN1. Ang II upregulated PARP1 expression, resulting in increased FN1 levels. Recombinant FN1 partially restored the progress of BRCA malignancy induced by the Ang II/PARP1 pathway. In vivo, candesartan reversed the progressive effect of chronic psychological stress on BRCA. In clinical samples, Ang II levels in both serum and tumor tissues are higher in stressed patients compared to control patients. Serum Ang II levels were positively correlated with chronic stress indicators. In conclusion, our study demonstrated that chronic psychological stress accelerates the malignancy of BRCA, and the AT1 inhibitor candesartan counteracts these effects by suppressing the Ang II-AT1 axis and the downstream PARP1/FN1/focal adhesion pathway.

RMI2 is a novel prognostic and predictive biomarker for breast cancer.

BACKGROUND: RecQ-mediated genome instability 2 (RMI2) maintains genome stability by promoting DNA damage repair. It has been reported to accelerate the progression of several tumors. However, the functional mechanism of RMI2 in breast cancer remains unclear. METHODS: Gene expression profiles were obtained from TCGA, GTEx, and GEO databases. The expression of RMI2 and its prognostic value in breast cancer was explored. In addition, we calculated pooled standardized mean deviation (SMD) and performed a summary receiver operating characteristic (sROC) curve analysis to further determine RMI2 expression status and diagnostic significance. The functions and related signaling pathways were investigated based on GO and KEGG analyses. The PPI network was constructed by combining the STRING database and Cytoscape software. Subsequently, in vitro assays were conducted to detect the effect of RMI2 on the proliferation and migration of breast cancer cells. RESULTS: The expression of RMI2 was markedly upregulated in breast cancer tissues relative to that in normal tissues. Moreover, pooled SMD further confirmed the overexpression of RMI2 in breast cancer (SMD = 1.29, 95% confidence interval (CI): 1.18-1.41, p = 0.000). The sROC curve analysis result suggested that RMI2 had a relatively high diagnostic ability in breast cancer (AUC = 0.87, 95% CI: 0.84-0.90). High RMI2 expression was associated with poor prognosis. GO and KEGG analyses revealed that RMI2 was closely related to cell adhesion, various enzyme activities, and PI3K/AKT signaling pathway. PPI analysis showed that RMI2 had interactions with proteins involved in DNA damage repair. knockdown of RMI2 remarkably inhibited the proliferation and migration of breast cancer cells, while overexpression of RMI2 exerted the opposite effects. Furthermore, we identified that RMI2 accelerates the proliferation and migration of breast cancer cells via activation of the PI3K/AKT pathway. CONCLUSION: The results suggest that RMI2 is a potential diagnostic and prognostic biomarker associated with cell proliferation and migration, and may be used as a novel therapeutic target for breast cancer in the future.

Cytoplasmic YAP1-mediated ESCRT-III assembly promotes autophagic cell death and is ubiquitinated by NEDD4L in breast cancer.

BACKGROUND: Nuclear Yes1-associated transcriptional regulator (YAP1) promotes tumor progression. However, the function of cytoplasmic YAP1 in breast cancer cells and its impact on the survival of breast cancer patients remain unclear. Our research aimed to explore the biological function of cytoplasmic YAP1 in breast cancer cells and the possibility of cytoplasmic YAP1 as a predictive marker of breast cancer survival. METHODS: We constructed cell mutant models, including NLS-YAP15SA (nuclear localized), YAP1S94A (incapable of binding to the TEA domain transcription factor family) and YAP1S127D (cytoplasmic localized), and used Cell Counting Kit-8 (CCK-8) assays, 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays, and Western blotting (WB) analysis to detect cell proliferation and apoptosis. The specific mechanism of cytoplasmic YAP1-mediated endosomal sorting complexes required for transport III (ESCRT-III) assembly was studied by co-immunoprecipitation, immunofluorescence staining, and WB analysis. Epigallocatechin gallate (EGCG) was used to simulate YAP1 retention in the cytoplasm in in vitro and in vivo experiments to study the function of cytoplasmic YAP1. YAP1 binding to NEDD4-like E3 ubiquitin protein ligase (NEDD4L) was identified using mass spectrometry and was verified in vitro. Breast tissue microarrays were used to analyze the relationship between cytoplasmic YAP1 expression and the survival of breast cancer patients. RESULTS: YAP1 was mainly expressed in the cytoplasm in breast cancer cells. Cytoplasmic YAP1 promoted autophagic death of breast cancer cells. Cytoplasmic YAP1 bound to the ESCRT-III complex subunits charged multivesicular body protein 2B (CHMP2B) and vacuolar protein sorting 4 homolog B (VPS4B), promoting assembly of CHMP2B-VPS4B and activating autophagosome formation. EGCG retained YAP1 in the cytoplasm, promoting the assembly of CHMP2B-VPS4B to promote autophagic death of breast cancer cells. YAP1 bound to NEDD4L, and NEDD4L mediated ubiquitination and degradation of YAP1. Breast tissue microarrays revealed that high levels of cytoplasmic YAP1 were beneficial to the survival of breast cancer patients. CONCLUSIONS: Cytoplasmic YAP1 mediated autophagic death of breast cancer cells by promoting assembly of the ESCRT-III complex; furthermore, we established a new breast cancer survival prediction model based on cytoplasmic YAP1 expression.

USF1-ATRAP-PBX3 Axis Promote Breast Cancer Glycolysis and Malignant Phenotype by Activating AKT/mTOR Signaling.

Angiotensin II type 1 receptor-associated protein (ATRAP) is widely expressed in different tissues and organs, although its mechanistic role in breast cancer remains unclear. Here, we show that ATRAP is highly expressed in breast cancer tissues. Its aberrant upregulation promotes breast cancer aggressiveness and is positively correlated with poor prognosis. Functional assays revealed that ATRAP participates in promoting cell growth, metastasis, and aerobic glycolysis, while microarray analysis showed that ATRAP can activate the AKT/mTOR signaling pathway in cancer progression. In addition, ATRAP was revealed to direct Ubiquitin-specific protease 14 (USP14)-mediated deubiquitination and stabilization of Pre-B cell leukemia homeobox 3 (PBX3). Importantly, ATRAP is a direct target of Upstream stimulatory factor 1 (USF1), and that ATRAP overexpression reverses the inhibitory effects of USF1 knockdown. Our study demonstrates the broad contribution of the USF1/ATRAP/PBX3 axis to breast cancer progression and provides a strong potential therapeutic target.

Correlation between 18F-FDG maximum standardized uptake value with CD147 expression in lung adenocarcinomas: a retrospective study.

BACKGROUND: The pro-tumoral action of the cluster of differentiation 147 (CD147), which is associated with the chemotherapy resistance of lung adenocarcinoma, is partly due to accelerated tumor cell glycolysis. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) metabolic parameters included maximal standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), which are non-invasive markers of the glucose metabolism of tumor cells in vivo. This study aimed to clarify the correlation between PET metabolic parameters and CD147 expression, and to evaluate the prognostic value of CD147 expression in resectable lung adenocarcinoma patients. METHODS: A total of 89 lung adenocarcinoma chemotherapy-naive patients who underwent 18F-fluorodeoxyglucose positron emission tomography and computerized tomography scan before pulmonary surgery were retrospectively analyzed. The PET metabolic parameters were calculated by 18F-FDG PET imaging, and CD147 expression was analyzed by immunohistochemistry. SUVmax, SUVmean, MTV, and TLG compared for their performance in predicting the expression of CD147 were illustrated with statistical analysis. All patients were then followed-up for survival analysis. RESULTS: The SUVmax was significantly correlated with the CD147 expression and was the primary predictor for the CD147 expression of lung adenocarcinoma. A cut-off value of the SUVmax, 9.77 allowed 85.1% sensitivity and 64.3% specificity for predicting the CD147 positive lung adenocarcinoma. CD147 expression was correlated with tumor differentiation and metastasis. Univariate survival analysis showed that CD147 expression was significantly associated with a shorter overall survival (OS) time. Multivariate analysis revealed that CD147 was an independent prognostic factor of lung adenocarcinoma patients. CONCLUSION: The SUVmax of a primary tumor measured with 18F-FDG PET may be a simple and non-invasive marker for predicting CD147 expression in lung adenocarcinoma. CD147 is an independent prognostic factor related to OS of postoperative lung adenocarcinoma patients.

Overexpression of connective tissue growth factor is associated with tumor progression and unfavorable prognosis in endometrial cancer.

OBJECTIVES: This study was to explore the prognostic value of connective tissue growth factor (CTGF) expression in endometrial cancer (EC). METHODS: We compared CTGF expression in 198 samples from patients with endometrial cancer and 50 samples from patients with healthy endometrial tissues as determined by immunohistochemistry. RESULTS: Expression of CTGF was significantly higher in endometrial cancers as compared to normal endometrial tissues. Positive CTGF expression displayed a strong association with CA125 level, histological grade, depth of myometrial invasion and the International Federation of Gynecology and Obstetrics (FIGO) stage. Our findings revealed histological grade, depth of myometrial invasion, FIGO stage, vascular/lymphatic invasion, and the CTGF expression are related to 5-year survival in patients with endometrial cancer. Positive CTGF expression, lymph node status, as well as vascular/lymphatic invasion, were identified as independent prognostic factors in endometrial cancer. CONCLUTIONS: Over-expression of CTGF is an independent prognostic factor that will allow the successful differentiation of high-risk population from the group of patients with stage III-IV endometrial cancer. The up-regulation of CTGF may contribute to the progression of endometrial cancer and serve as a new prognostic biomarker in patients with endometrial cancer survival.

Longitudinal Trends in Anxiety, Depression, and Quality of Life During Different Intermittent Periods of Adjuvant Breast Cancer Chemotherapy.

BACKGROUND: Chemotherapy (CT) is an important adjuvant treatment that has been widely used for breast cancer (BC) patients. However, no research has focused on trends in emotions and quality of life (QOL) during intermittent periods between CT sessions that are critical for recovery. OBJECTIVE: The aim of this study was to investigate longitudinal trends in anxiety, depression, and QOL during the different intermittent periods between adjuvant CT for BC. METHODS: A longitudinal study design was adopted. Eighty-eight women undergoing CT for BC were selected using a purposive sampling method, and they completed the Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and Functional Assessment of Cancer Therapy-Breast (FACT-B) at 5 points. A repeated-measures analysis-of-variance model was used to compare anxiety, depression, and QOL at different time points. RESULTS: The results showed a significant difference in SAS (F = 187.78, P < .00), SDS (F = 263.07, P < .00), and FACT-B (F = 140.82, P < .00) scores at the 5 time points. The SAS and SDS scores were highest at T3, whereas the FACT-B score was lowest at T3. CONCLUSIONS: The BC patients had psychological distress during intermittent periods between adjuvant CT, as evidenced by anxiety and depression, which were highest in the third cycle. Meanwhile, QOL was lowest at the third CT cycle and highest at the first CT cycle. IMPLICATIONS FOR PRACTICE: Clinical staff should focus on critical time periods during CT, particularly during the third cycle, and provide additional support to patients to ensure that CT is delivered in an optimal fashion.

Elevated HABP1 protein expression correlates with progression and poor survival in patients with gastric cancer.

BACKGROUND: Hyaluronic acid-binding protein 1 (HABP1/gC1qR/p32) has been recently implicated in oncogenesis and cancer progression in various malignancies; however, its clinical role in gastric cancer (GC) is still unclear. PATIENTS AND METHODS: First, HABP1 expression was determined by Western blot analysis and immunohistochemistry. Then, we evaluated the expression of HABP1 and its clinical significance in tumor tissues from 181 patients with GC. RESULTS: Expression of HABP1 protein in GC tissues was noticeably higher than that in adjacent nonneoplastic tissues (P=0.018). Increased HABP1 expression was significantly associated with tumor, node, and metastasis (TNM) stage (P=0.006), depth of invasion (P=0.001), lymph node metastasis (P=0.001), liver metastasis (P=0.024), and peritoneum metastasis (P=0.009). Patients with high expression of HABP1 had poor overall survival rate (P<0.001). In addition, histologic grade (P=0.017), TNM stage (P<0.001), Borrmann grouping (P<0.001), depth of invasion (P<0.001), lymph node metastasis (P<0.001), liver metastasis (P=0.010), and tumor size (P<0.001) were independent prognostic factors for overall survival. Multivariate Cox regression analysis revealed that HABP1 (P=0.004), histologic grade (P=0.047), TNM stage (P<0.001), Borrmann grouping (P<0.001), and liver metastasis (P=0.038) were independent factors for overall survival in patients with GC. CONCLUSION: These findings demonstrated that HABP1 was an indicator for GC progression and poor survival, which highlighted its potential role as a therapeutic target for GCs.

Expression and prognostic value of SFRP1 and ß-catenin in patients with glioblastoma.

The roles of secreted frizzled-related protein-1 (SFRP1) and ß-catenin in human cancer have been widely studied, and it has recently been demonstrated that these proteins are associated with numerous human carcinomas. However, their clinical significance in glioblastoma multiforme (GBM) has not been examined. The current study aimed to analyze the correlation between the expression of SFRP1 and ß-catenin, and clinicopathological characteristics in GBM patients. The expression of SFRP1 and ß-catenin was assessed by immunohistochemistry in 113 samples of GBM and 40 normal brain tissues. Compared with normal brain tissues, GBM tissues exhibited significantly lower expression of SFRP1, and higher expression of ß-catenin (both P<0.05). A Kaplan-Meier analysis revealed that patients with positive SFRP1 expression had a significantly longer overall survival (OS) time relative to those with negative SFRP1 expression (P<0.000), and that patients with positive ß-catenin expression had a shorter OS time than those with negative ß-catenin expression (P<0.000). A multivariate Cox regression analysis indicated that adjuvant treatment, SFRP1 expression and ß-catenin expression were independent prognostic factors for OS (P<0.000, P=0.008 and P=0.001, respectively) in patients with GBM. The current data suggest that expression of SFRP1 and ß-catenin may be considered significant prognostic indicators for patients with GBM.