Effects of physical exercise on biomarkers of oxidative stress in healthy subjects: A meta-analysis of randomized controlled trials.

This meta-analysis investigated the effect of physical exercise (PE) on the levels of oxidative biomarkers in randomized controlled trials (RCTs) involving healthy subjects. We searched five databases for articles until May 1, 2023. A random-effect meta-analysis, subgroup analysis, meta-regressions as well as trim and fill method were conducted using STATA 11.0, involving ten articles. According to the results of the meta-analysis, PE had no significant effect on superoxide dismutase (SOD), glutathione peroxidase, and catalase levels. PE induced significant increase in total antioxidant status (standardized mean difference [SMD] 1.53, 95% CI 0.73-2.32), and PE could significantly reduce the level of malondialdehyde (MDA) (SMD -1.11, 95% CI -2.15 to -0.06). Sensitivity analyses and subgroup analyses showed that male participants, body mass index (BMI) <25, exercise duration between 1 and 12 weeks, resistance exercise or multicomponent exercise, and exercise of low or moderate intensity were associated with a significant PE-induced decrease in MDA concentrations. Meta-regression analysis identified the age of the participants as a confounder of the effect of PE on SOD levels. The older age of the subjects was associated in a gradient fashion with incident SOD levels. Further RCTs are required to investigate the optimal PE protocol for people of different ages and BMI as well as the effect of PE on oxidative stress.

Low skeletal muscle mass index and all-cause mortality risk in adults: A systematic review and meta-analysis of prospective cohort studies.

OBJECTIVE: The relationship between low skeletal muscle mass index (SMI) and all-cause mortality risk in the general adults remains unclear. Our study was conducted to examine and quantify the associations between low SMI and all-cause mortality risks. METHODS: PubMed, Web of Science, and Cochrane Library for primary data sources and references to relevant publications retrieved until 1 April 2023. A random-effect model, subgroup analyses, meta-regression, sensitivity analysis, and publication bias were conducted using STATA 16.0. RESULTS: Sixteen prospective studies were included in the meta-analysis of low SMI and the risk of all-cause mortality. A total of 11696 deaths were ascertained among 81358 participants during the 3 to 14.4 years follow-up. The pooled RR of all-cause mortality risk was 1.57 (95% CI, 1.25 to 1.96, P < 0.001) across the lowest to the normal muscle mass category. The results of meta-regression showed that BMI (P = 0.086) might be sources of heterogeneity between studies. Subgroup analysis showed that low SMI was significantly associated with an increased risk of all-cause mortality in studies with a body mass index (BMI) between 18.5 to 25 (1.34, 95% CI, 1.24-1.45, P<0.001), 25 to 30 (1.91, 95% CI, 1.16-3.15, P = 0.011), and over 30 (2.58, 95% CI, 1.20-5.54 P = 0.015). CONCLUSIONS: Low SMI was significantly associated with the increased risk of all-cause mortality, and the risk of all-cause mortality associated with low SMI was higher in adults with a higher BMI. Low SMI Prevention and treatment might be significant for reducing mortality risk and promoting healthy longevity.

Analysis and prediction model of ferroptosis related genes in breast cancer.

Background: The prognosis of patients with breast cancer (BRCA) is difficult to predict because of the high degree of heterogeneity and complex etiological factors. Ferroptosis, an iron-dependent, new form of cell death, plays an important role in regulation of tumor growth and progression. The aim of this study was to clarify the predictive value of ferroptosis-related genes in the overall survival of patients with BRCA. Methods: The messenger RNA expression profile and clinical information of patients with BRCA were collected from The Cancer Genome Atlas (TCGA) database. The differences between BRCA and adjacent normal tissues were analyzed, and candidates with differentially expressed ferroptosis-related genes were identified. Through Cox and LASSO analyses, the prognostic genetic characteristics of ferroptosis-related genes were established. Lastly, according to the median risk score, the patients were divided into high-risk and low-risk groups, a nomogram was constructed, and the prediction accuracy was tested. Results: It was determined that the four ferroptosis related genes had a significant difference in survival in BRCA (P<0.05); a prognostic model was constructed based on the four ferroptosis related genes, and the overall survival of patients in the high-risk group was significantly worse (P<0.05). The four-gene nomogram can quantify the contribution of each index to survival, and the calibration chart shows high prediction accuracy. Conclusions: This study constructed four ferroptosis related gene characteristics and nomogram, which can effectively predict the prognosis of BRCA patients and provide new insights for future anti-cancer treatments based on ferroptosis targets.

Retracted: Polyacrylamide Hydrogel Injection for Breast Augmentation: Another Injectable Failure.

This publication has been retracted by the Editor as it erroneously describes the effects of an injectable polyacrylamide gel.Reference:Zhenxiang Wang, Shirong Li, Lingli Wang, Shu Zhang, Yan Jiang, Jinping Chen, Donglin Luo. Polyacrylamide Hydrogel Injection for Breast Augmentation: Another Injectable Failure. Med Sci Monit, 2012; 18(6): CR399-408. DOI: 10.12659/MSM.882910.

Assessing the Variations in Breast/Ovarian Cancer Risk for Chinese BRCA1/2 Carriers.

Background: Cancer risks vary in different BRCA1/2 mutations. We are interested in identifying regions associated with elevated/reduced risks of breast/ovarian cancers in the Chinese population and comparing with previously reported Caucasian-based breast/ovarian cancer cluster regions (OCCR/BCCR). We also aim to characterize the distribution and estimate the cancer risks of different Chinese recurrent mutations. Methods: A total of 3,641 cancer-free women and 4,278 female cancer patients were included in the study. Germline BRCA1/2 status was detected with amplicon-based next-generation sequencing. We calculated the odds ratio (OR) of breast cancer and OR of ovarian cancer, and their ratio of the two ORs (ROR) for each region. ROR >1 indicated elevated odds of breast cancer and/or decreasing odds of ovarian cancer, and vice versa. The frequency, distribution, and penetrance of six known Chinese founder mutations were characterized, respectively. Haplotype analysis and age estimation were performed on the most prevalent founder mutation BRCA1: c.5470_5477del. Results: A total of 729 subjects were detected with germline BRCA1/2 deleterious mutations. The putative Chinese OCCR/BCCR partially overlapped with Caucasian-based OCCR/BCCR and shared structural-functional characteristics. The six known Chinese founder mutations greatly vary in both distribution and penetrance. The two widely spread mutations are estimated to convey low penetrance, while the area-restricted founder mutations seemed to confer higher/complete penetrance. BRCA1: c.5470_5477del is estimated to have emerged ∼2,090 years ago (70 B.C.) during the Han dynasty. Conclusions: BRCA1/2 carriers with different genotypes have significantly different cancer risks. An optimal risk assessment should be mutation specific, rather than concerning a single figure.

METTL3/IGF2BP3 axis inhibits tumor immune surveillance by upregulating N6-methyladenosine modification of PD-L1 mRNA in breast cancer.

BACKGROUND: Continual expression of PD-L1 in tumor cells is critical for tumor immune escape and host T cell exhaustion, however, knowledge on its clinical benefits through inhibition is limited in breast cancer. N6-methyladenosine (m6A) plays a crucial role in multiple biological activities. Our study aimed to investigate the regulatory role of the m6A modification in PD-L1 expression and immune surveillance in breast cancer. METHODS: MeRIP-seq and epitranscriptomic microarray identified that PD-L1 is the downstream target of METTL3. MeRIP-qPCR, absolute quantification of m6A modification assay, and RIP-qPCR were used to examine the molecular mechanism underlying METTL3/m6A/IGF2BP3 signaling axis in PD-L1 expression. B-NDG and BALB/c mice were used to construct xenograft tumor models to verify the phenotypes upon METTL3 and IGF2BP3 silencing. In addition, breast cancer tissue microarray was used to analyze the correlation between PD-L1 and METTL3 or IGF2BP3 expression. RESULTS: We identified that PD-L1 was a downstream target of METTL3-mediated m6A modification in breast cancer cells. METTL3 knockdown significantly abolished m6A modification and reduced stabilization of PD-L1 mRNA. Additionally, METTL3-mediated PD-L1 mRNA activation was m6A-IGF2BP3-dependent. Moreover, inhibition of METTL3 or IGF2BP3 enhanced anti-tumor immunity through PD-L1-mediated T cell activation, exhaustion, and infiltration both in vitro and in vivo. PD-L1 expression was also positively correlated with METTL3 and IGF2BP3 expression in breast cancer tissues. CONCLUSION: Our study suggested that METTL3 could post-transcriptionally upregulate PD-L1 expression in an m6A-IGF2BP3-dependent manner to further promote stabilization of PD-L1 mRNA, which may have important implications for new and efficient therapeutic strategies in the tumor immunotherapy.

Pyrotinib treatment enhances the radiosensitivity in HER2-positive brain metastatic breast cancer patients.

Brain metastasis is a common cause of death in HER2-positive breast cancer patients. Currently, it is mainly treated by whole-brain radiotherapy. Pyrotinib is an irreversible pan-ErbB inhibitor, which has demonstrated promising tumor-suppressing activity and acceptable tolerance in previous phase trials. In the present study, we evaluated the efficacy of pyrotinib on HER2-positive brain metastatic breast cancer patients treated with whole-brain radiotherapy. A total of 20 such patients were separated into pyrotinib plus capecitabine and capecitabine-only groups in a 1:1 ratio. All patients met either the primary or secondary endpoints. Oral admission of pyrotinib together with radiotherapy can significantly increase the overall response rate, progression-free survival, time to progression and duration of response of HER2+ brain metastatic breast cancer patients, without causing extra adverse events. In addition, pyrotinib can enhance the radiosensitivity of in-vitro cultured HER2+ breast cancer cell lines. The outcome of our study suggests that pyrotinib might be an effective medication to enhance the tumor radiosensitivity of HER2-positive brain metastatic breast cancer patients.

Analysis of Circulating Tumor DNA to Predict Neoadjuvant Therapy Effectiveness and Breast Cancer Recurrence.

PURPOSE: Real-time detection and intervention can be used as potential measures to markedly decrease breast cancer mortality. Assessment of circulating tumor DNA (ctDNA) may offer great benefits for the management of breast cancer over time. However, the use of ctDNA to predict the effectiveness of neoadjuvant treatment and recurrence of breast cancer has rarely been studied. METHODS: We prospectively recruited 31 breast cancer patients with 4 subtypes. Three time points were set in this study, including before any therapy (C1), during surgery (T), and six months after surgery (C2). We collected peripheral blood samples from all 31 patients at C1, tumor tissue from all 31 patients at T, and peripheral blood samples from 25 patients at C2. Targeted 727-gene panel sequencing was performed on ctDNA from all blood samples and tissue DNA from all tissue samples. Somatic mutations were detected and analyzed using a reference standard pipeline. Statistical analysis was performed to identify possible associations between ctDNA profiles and clinical outcomes. RESULTS: In total, we detected 159, 271, and 70 somatic mutations in 30 C1 samples, 31 T samples, and 12 C2 samples, respectively. We identified specific genes, such as PIK3CA, TP53, and KMT2C, which were highly mutated in the tissue samples. Furthermore, mutated KMT2C observed in ctDNA of the C2 samples may be an indicator of breast cancer recurrence. CONCLUSION: Our study highlights the potential of ctDNA analysis at different timepoints for assessing tumor progression and treatment effectiveness, as well as prediction of breast cancer recurrence.

Low-concentration DMSO accelerates skin wound healing by Akt/mTOR-mediated cell proliferation and migration in diabetic mice.

BACKGROUND AND PURPOSE: DMSO has been found to promote tissue repair. However, the role of DMSO in diabetic skin wound healing and the underlying molecular mechanisms are still unclear. EXPERIMENTAL APPROACH: The effects of DMSO on wound healing were evaluated by HE staining, immunohistochemistry and collagen staining using a wound model of full-thickness skin resection on the backs of non-diabetic or diabetic mice. Real-time cell analysis and 5-ethynyl-2'-deoxyuridine incorporation assays were used to study the effect of DMSO on primary fibroblast proliferation. A transwell assay was used to investigate keratinocyte migration. The associated signalling pathway was identified by western blotting and inhibitor blocking. The effect of DMSO on the translation rate of downstream target genes was studied by RT-qPCR of polyribosome mRNA. KEY RESULTS: We found that low-concentration DMSO significantly accelerated skin wound closure by promoting fibroblast proliferation in both nondiabetic and diabetic mice. In addition, increased migration of keratinocytes may also contribute to accelerated wound healing, which was stimulated by increased TGF-ß1 secretion from fibroblasts. Furthermore, we demonstrated that this effect of DMSO depends on Akt/mTOR-mediated translational control and the promotion of the translation of a set of cell proliferation-related genes. As expected, DMSO-induced wound healing and cell proliferation were impaired by rapamycin, an inhibitor of Akt/mTOR signalling. CONCLUSION AND IMPLICATIONS: DMSO can promote skin wound healing in diabetic mice by activating the Akt/mTOR pathway. Low-concentration DMSO presents an alternative medication for chronic cutaneous wounds, especially for diabetic patients.

Whole Exome Sequencing in the Male Breast Cancer with Prolactinoma: A Case Report and Literature Review.

Male breast cancer (MBC) is rare and accounts for approximately 1% of all breast cancer cases worldwide. Previous studies have suggested that several factors significantly increase the risk of MBC. Prolactinoma has the highest incidence rate among patients with functional pituitary tumors. However, whether prolactinoma is involved in the onset and progression of breast cancer remains unclear. To date, there are only five case reports globally on MBC with concurrent prolactinoma. We hereby describe the first case of MBC with prolactinoma in China. We also explored the patient's genetic profile using whole exome sequencing. Our findings may help advance our understanding of the molecular pathogenesis of MBC. Further molecular analyses of such cases are warranted to improve auxiliary molecular diagnostic methods and targeted therapy for MBC.

MicroRNA-374c-5p inhibits the development of breast cancer through TATA-box binding protein associated factor 7-mediated transcriptional regulation of DEP domain containing 1.

Breast cancer is the most pervasive cancer tormenting women, with increasing incidence and mortality rates year after year. MicroRNAs (miRNAs) with abnormal expression has various effects in biological processes and progression in diverse tumors. Nevertheless, it is vitally crucial for us to inspect more underlying molecular mechanisms for the therapy of patients with breast cancer. In the paper, we inquired the expression level and potential regulation mechanism of miR-374c-5p in breast cancer. Our research found out that miR-374c-5p was low-level expressed in breast cancer. Upregulation of miR-374c-5p repressed cell proliferation, migration, and also epithelial-mesenchymal transition (EMT), and induced cell apoptosis of breast cancer cells. Further, we concluded that miR-374c-5p interacted with TAF7 and downregulated its expression. Moreover, miR-374c-5p modulated DEP domain containing 1 (DEPDC1) through mediating TAF7. Finally, rescue assays represented that miR-374c-5p suppressed breast cancer development via TAF7-mediated transcriptional regulation of DEPDC1. We uncovered that overexpressed miR-374c-5p inhibited the development of breast cancer via TAF7-regulated transcriptional regulation of DEPDC1, which may be a novel and vital proportion of cancer diagnosis and treatment strategies.

The Chinese herb Xiaoaiping protects against breast cancer chemotherapy-induced alopecia and other side effects: a randomized controlled trial.

OBJECTIVE: To investigate the effects of the Chinese herbal medicine Xiaoaiping to treat chemotherapy-induced side effects in breast cancer patients. METHODS: Ninety-three adult patients who attended our hospital and met the entry criteria from January 2016 to December 2017 were included. Patients were randomly divided into the control group (routine chemotherapy only) and the combined group (routine chemotherapy and Xiaoaiping). Demographic data and clinical variables were collected, and side effects including alopecia, nausea and vomiting, diarrhea, white blood cell (WBC) count, aspartate aminotransferase (AST) levels, and the quality of life were evaluated. RESULTS: Basic clinical characteristics were not different between the groups. There were significantly fewer patients with alopecia grade 3-4, but significantly more patients with alopecia grade 1-2, in the combined group compared with the control group. Disease-free time for alopecia was longer in the combined compared with the control group. Overall, the side effects were significantly more serious in the control compared with the combined group. Patients in the combined group had better quality of life than the control patients. CONCLUSION: Xiaoaiping can improve alopecia, nausea and vomiting, and diarrhea symptoms, WBC count, AST levels, and the quality of life in breast cancer patients.

Degradation of tetracyclines in manure-amended soil and their uptake by litchi (Litchi chinensis Sonn.).

The environmental and human health risk posed by veterinary antibiotics is of global concern. Antibiotic uptake by herbal plants has been studied, but little is known about perennial woody fruit crops. Litchi (Litchi chinensis Sonn.), a longevial fruit tree, is routinely fertilized with animal manure and, therefore, may be at risk of antibiotic uptake into its fruits. This study investigated the degradation of chlortetracycline and doxycycline present in manure used to amend orchard soil, and their subsequent assimilation by litchi plant, as affected by manure application rate. The results show that half-lives of chlortetracycline and doxycycline in soil were decreased by increased manure rate, with an average of 27 and 59 days, respectively. Chlortetracycline was readily transported to litchi shoots and increased with the growth of litchi plants. Doxycycline predominantly remained in the roots, and underwent growth dilution in the plants. The two tetracyclines could not be detected in fruits from litchi trees when applied with manures, at various rates, over 2 years. For litchi, chlortetracycline may pose human health risk through manure application, but doxycycline is unlikely to do so. Long-term field experiments are required to monitor antibiotic accumulation in fruits of perennial fruit trees fertilized with animal manure.

Lobaplatin inhibits breast cancer progression, cell proliferation while it induces cell apoptosis by downregulating MTDH expression.

OBJECTIVE: Lobaplatin shows antitumor activity against a wide range of tumors, including metastatic breast cancer (BCa). The overexpression of metadherin (MTDH) is associated with poor prognosis of BCa patients. This study was designed to investigate the effect of lobaplatin on MCF-7 cell proliferation and its association with MTDH expression. PATIENTS AND METHODS: Clinical treatment for BCa using lobaplatin, in combination with other general chemotherapy drugs, was administered to 32 BCa patients. The safety, effectiveness, and prognosis in lobaplatin-treated BCa patients were compared with those in controls (n=32). In vitro experiments were performed in MCF-7 cells to investigate the effect of lobaplatin on cell proliferation, apoptosis, and MTDH expression. RESULTS: We found the intraoperative local chemotherapy using lobaplatin was safe and effective for BCa treatment, in comparison with the patients administered general chemotherapy drugs. Treatment of MCF-7 cell cultures with lobaplatin significantly reduced cell proliferation and increased cell apoptotic percentage. The expression of MTDH and Bcl-2 was inhibited by lobaplatin and that of Bax was increased by lobaplatin. Moreover, we observed the inhibition of MTDH by shRNA reduced cell proliferation and enhanced cell apoptosis. CONCLUSION: Lobaplatin was a safe and effective adjuvant chemotherapy for BCa. The effect of lobaplatin on inhibiting MCF-7 cell proliferation and inducing cell apoptosis might be, as least in part, mediated by suppressing the expression of oncogene MTDH.

Steroid receptor coactivator-1 interacts with NF-κB to increase VEGFC levels in human thyroid cancer.

Thyroid cancer is the most common endocrine cancer, and has a high incidence of lymphatic metastasis. Vascular endothelial growth factor C (VEGFC) is essential for development of lymphatic vessels and lymphatic metastases during carcinogenesis. Steroid receptor coactivator-1 (SRC-1) interacts with nuclear receptors and transcription factors to promote tumor proliferation and metastasis. However, the correlation between SRC-1 and VEGFC levels in the lymphatic metastases of thyroid cancer remains unclear. We analyzed 20-paired specimens of thyroid cancer tissue and normal thyroid tissue and found increased levels of SRC-1 and VEGFC proteins in 13/20 and 15/20 thyroid cancer specimens, respectively, when compared with those levels in specimens of normal thyroid tissue. A high level of SRC-1 expression was positively correlated with VEGFC and lymphatic endothelial cell marker LYVE-1 expression. Papillary thyroid carcinoma cell line TPC-1 displayed high levels of SRC-1 and VEGFC expression and was selected for stable knockdown of SRC-1 in vitro Inhibition of SRC-1 significantly reduced the VEGFC levels in TPC-1 cells. We found that SRC-1 binds to transcription factor NF-kB (p50/p65), and that this coactivation complex directly promoted VEGFC transcription, which could be abrogated by SRC-1 knockdown. Up-regulated NF-kB signaling was also confirmed in thyroid cancer tissues. In vivo studies showed that SRC-1 knockdown restricted tumor growth, reduced the numbers of LYVE-1-positive lymphatic vessels, and decreased the levels of VEGFC in tumor tissues. These results suggest a tumorigenic role for SRC-1 in thyroid cancer via its ability to regulate VEGFC expression.

PI3K inhibitors IC87114 inhibits the migration and invasion of thyroid cancer cell in vitro and in vivo.

Thyroid cancer is currently the most common endocrine malignancies, and PI3K/Akt pathway play an important role during its initiation and development. IC87114 is an inhibitor of PI3K/Akt pathway. Little is known about the role of IC87114 in the initiation and progression of thyroid cancer. Here, we demonstrated that IC87114 significantly inhibited both the migration and invasion of thyroid cancer cells, which can be mediated by inhibition of PI3K/Akt pathway. These results suggest that application of IC87114 may prove to be a particularly effective treatment for thyroid cancer.

Knockdown of lncRNA-PANDAR suppresses the proliferation, cell cycle and promotes apoptosis in thyroid cancer cells.

Long non-coding RNAs (lncRNAs) have been found to show important regulatory roles in various human cancers. Lnc-RNA PANDAR is a novel identified lncRNA that was previously reported to show abnormal expression pattern in various cancers. However, little is known of its expression and biological function in thyroid cancer. Here, we used the quantitative real-time PCR (qRT-PCR) to determine the expression of PANDAR in 64 thyroid cancer tissues. We found that expression of PANDAR was up-regulated in thyroid cancer tissues compared with adjacent non-tumor tissues. Functional assays in vitro demonstrated that knockdown of PANDAR could inhibit proliferation, cell cycle progression, induces the apoptosis, inhibit invasion of thyroid cancer cells. Thus, our study provides evidence that PANDAR may function as a potential target for treatment for patients with thyroid cancer.

Low expression of long non-coding RNA GAS5 is associated with poor prognosis of patients with thyroid cancer.

The study aims to investigate the role of long non-coding RNA (lncRNA) GAS5 in the diagnosis and prognosis of patients suffering from thyroid cancer (TC). A total of 212 patients with TC and 61 patients with benign thyroid tumor were enrolled in the study. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the lncRNA GAS5 expression in TC and benign tumor tissues. All TC patients were categorized into high-risk and low-risk groups according to the MACIS, AGES and AMES prognostic scoring system. A 5-year follow-up was conducted in order to determine the disease free survival (DFS) rates and overall survival (OS) rates. The associations between lncRNA GAS5 expression and prognosis of TC patients were analyzed by The Kaplan-Meier survival curves and the Cox regression models. There was a decrease in the lncRNA GAS5 expression in TC tissues in comparison to benign tumor tissues. Expression of lncRNA GAS5 showed significant association with tumor node metastasis (TNM) staging, lymph node metastasis and the multiple cancer foci of TC. AMES high-risk patients showed a decreased expression of lncRNA GAS5 expression than the AMES low-risk patients. The AGES and MACIS high-risk patients showed lower lncRNA GAS5 expression than low-risk patients. The survival rate of TC patients with high lncRNA GAS5 expression was higher than that of TC patients with low lncRNA GAS5 expression during the DFS and OS periods. Cox regression analysis indicated that lncRNA GAS5 expression, TNM staging, lymph node metastasis and multiple cancer foci were independent risk factors for poor prognosis in TC patients. LncRNA GAS5 may be closely related to the diagnosis and prognosis of TC.

Demethylation of miR-495 inhibits cell proliferation, migration and promotes apoptosis by targeting STAT-3 in breast cancer.

In breast cancer (BC), silencing of miRNA genes due to miRNA gene promoter methylation are the important mechanisms directly contributing to tumorigenesis and tumor progression. miRNA-495 (miR-495) has been reported to be a tumor suppressor gene in various cancers, but its role and regulation in BC remains unclear. In the present study, the level of miR-495 was inversely correlated with the expression of STAT-3 in BC tissues and cell lines. miR-495 can directly target 3'-UTR of STAT-3 mRNA and thereby decrease the expression of STAT-3 in MCF-7 and HCC1973 cells by Targetscan and Dual-luciferase assay. We further analyzed miR-495 promoter methylation by sodium bisulfite sequencing method (BSP), and found DNA methyltransferase inhibitor, 5-AzaC concomitantly upregulated expression of miR-495 and downregulated its target gene STAT-3 and its downstream target VEGF. Furthermore, we further observed that 5-AzaC treatment, miR-495 mimics and STAT-3 knockdown significantly inhibited cell function in breast cancer by Transwell assay, EdU flow cytometry, Annexin V-FITC/PI combined with flow cytometry and Hoechst staining. Taken together, our data are first to demonstrate that the miR-495 is silenced due to promoter methylation in breast cancer. DNA methyltransferase inhibitor 5-AzaC could reverse miR­495 (suppressor gene) and STAT-3 (oncogene). The anticancer properties of 5-AzaC were preliminarily confirmed in breast cancer.

Does dual HER-2 blockade treatment increase the risk of severe toxicities of special interests in breast cancer patients: A meta-analysis of randomized controlled trials.

Although dual HER-2 blockade treatment could offer greater clinical efficacy in breast cancer, the risk of severe toxicities of special interest related to this combined regimen in breast cancer remained unknown. We systematically searched public databases (MEDLINE, EMBASE, Cochrane library) to identify relevant studies that comparing anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) with dual HER-2 blockade treatment (pertuzumab plus trastuzumab or trastuzumab plus lapatinib) in breast cancer. A total of 11,941 breast cancer patients from 9 trials were included for analysis. Meta-analysis showed that dual HER2 blockade treatment significantly increased the risk of severe diarrhea (OR 2.52, p<0.001) and treatment discontinuation (OR 1.52, p=0.014), but not for severe rash (OR 1.06, p=0.81), liver toxicities (OR 1.16, p=0.28), CHF (OR 1.46, p=0.09), LVEF decline (OR 1.09, p=0.40) and FAEs (OR 0.97, p=0.91). Similar results were observed in sub-group analysis according to anti-HER2 regimens in terms of severe diarrhea and treatment discontinuation. Additionally, trastuzumab plus lapatinib significantly increased the risk of LVEF decline in comparison with lapatinib alone (OR 1.48, p=0.002). Our analysis indicated that dual anti-HER2 blockade treatment significantly increased the risk of developing severe diarrhea and treatment discontinuation in comparison with anti-HER2 monotherapy. These were no evidence of an increased risk of fatal adverse events with dual-HER2 blockade treatment.