Long non-coding RNAs (lncRNAs) play an important role in cancer metastasis. Exploring metastasis-associated lncRNAs and developing effective strategy for targeted regulation of lncRNA function in vivo are of utmost importance for the treatment of metastatic cancer, which however remains a big challenge. Herein, we identified a new functional lncRNA (denoted lncBCMA), which could stabilize the expression of eukaryotic translation elongation factor 1A1 (eEF1A1) via antagonizing its ubiquitination to promote triple-negative breast cancer (TNBC) growth and metastasis. Based on this regulatory mechanism, an endosomal pH-responsive nanoparticle (NP) platform was engineered for systemic lncBCMA siRNA (siBCMA) delivery. This NPs-mediated siBCMA delivery could effectively silence lncBCMA expression and promote eEF1A1 ubiquitination, thereby leading to a significant inhibition of TNBC tumor growth and metastasis. These findings show that lncBCMA could be used as a potential biomarker to predict the prognosis of TNBC patients and NPs-mediated lncBCMA silencing could be an effective strategy for metastatic TNBC treatment.

Purpose: This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in metastatic breast cancer (MBC) patients. Materials and Methods: The meta-analysis of randomized clinical trials (RCTs) and propensity score matching of multicenter cohort study evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. This study is registered with PROSPERO: CRD42017071858 and ClinicalTrials.gov: NCT04258163. Results: A total of 2,867 patients from 15 RCTs and 760 patients from multicenter cohort were included. The results from meta-analysis showed that chemotherapy maintenance improved progression-free survival (PFS) (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.54 to 0.73; p < 0.001; moderate-quality evidence) and overall survival (OS) (HR, 0.87; 95% CI 0.78 to 0.97; p=0.016; high-quality evidence) than observation. In the cohort study, for hormone receptor–positive MBC patients, chemotherapy maintenance improved PFS (HR, 0.67; 95% CI, 0.52 to 0.85; p < 0.001) and OS (HR, 0.55; 95% CI 0.42 to 0.73; p < 0.001) compared with observation, and endocrine therapy maintenance also improved PFS (HR, 0.65; 95% CI, 0.53 to 0.80; p < 0.001) and OS (HR, 0.55; 95% CI, 0.44 to 0.69; p < 0.001). There were no differences between chemotherapy and endocrine therapy maintenance in PFS and OS (all p > 0.05). Regardless of the continuum or switch maintenance therapy, showed prolonged survival in MBC patients who were response to first-line treatment. Conclusion This study provided evidences for survival benefits of chemotherapy and endocrine therapy maintenance in MBC patients, and there was no difference efficacy between chemotherapy and endocrine therapy maintenance for hormone receptor–positive patients.

Objective:To explore the correlation between immediate hypersensitivity induced by pegylated liposomal doxorubicin (PLD) and the plasma anti-polyethylene glycol (anti-PEG) antibody in advanced breast cancer patients.Methods:The study was designed as a prospective and noninterventional study. The subjects were selected from advanced breast cancer patients in Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, who received monotherapy with PLD (an IV infusion of PLD 50 mg/m 2 in 5% glucose solution 250 ml for 90 minutes without pretreatment with dexamethasone or other drugs). Anti-PEG antibody before administration were detected for all the patients and antibody level >2 ng/L was defined as positive. Blood in patients who had hypersensitivity within 30 minutes after the start of infusion was collected (finding the opportunity as soon as possible) and IgE, C3, and C4 levels in serum were detected. According to whether there was an immediate hypersensitivity reaction, the patients were divided into hypersensitivity group and non-hypersensitivity group and the clinical characteristics and plasma anti-PEG antibody carrying status in patients between the 2 groups were compared; according to anti-PEG antibody carrying status, the patients were divided into anti-PEG antibody positive group and negative group and the clinical characteristics and the incidence of hypersensitivity in patients between the 2 groups were compared. Results:A total of 12 patients were included in the study, aged from 37 to 68 years with a median age of 50 (37-68) years. Ten patients had previously used non-pegylated anthracyclines and the median cumulative dose was 329 (185, 418) mg/m 2 after a doxorubicin equivalent dose conversion. Seven patients developed hypersensitivity within 2-18 minutes after the start of infusion. Between the hypersensitivity group and the non-hypersensitivity group, differences in clinical characteristics such as age, height, weight, body surface area, previous application of anthracyclines, and the cumulative doses in patients were not significant (all P>0.05); the difference in positive rate of anti-PEG antibodies in patients was also not statistically significant (4/7 vs. 2/5, P=1.000). Among the 12 patients, 6 were positive for anti-PEG antibody and 6 were negative and the differences in the above-mentioned clinical characteristics or the incidence of hypersensitivity (3/6 vs. 4/6) in patients between the 2 groups (all P>0.05) were not significant. In the hypersensitivity group, IgE, C3, and C4 levels in serum were detected in 4 patients. Two patients with positive anti-PEG antibody had increased IgE levels (404 and 545 μg/L, respectively), 1 of which had also increased C4 level (486 mg/L); the other 2 patients with negative anti-PEG antibody had normal IgE, C3, and C4 levels. Conclusions:It has not been found that PLD-induced immediate hypersensitivity is related to the anti-PEG antibody, which may be due to the small sample size of the study. It cannot be ruled out that anti-PEG antibody may be involved in the induction of the IgE-mediated immediate hypersensitivity, which may also be mediated by complement in some patients.

Objective:To explore the correlation between immediate hypersensitivity induced by pegylated liposomal doxorubicin (PLD) and the plasma anti-polyethylene glycol (anti-PEG) antibody in advanced breast cancer patients.Methods:The study was designed as a prospective and noninterventional study. The subjects were selected from advanced breast cancer patients in Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, who received monotherapy with PLD (an IV infusion of PLD 50 mg/m 2 in 5% glucose solution 250 ml for 90 minutes without pretreatment with dexamethasone or other drugs). Anti-PEG antibody before administration were detected for all the patients and antibody level >2 ng/L was defined as positive. Blood in patients who had hypersensitivity within 30 minutes after the start of infusion was collected (finding the opportunity as soon as possible) and IgE, C3, and C4 levels in serum were detected. According to whether there was an immediate hypersensitivity reaction, the patients were divided into hypersensitivity group and non-hypersensitivity group and the clinical characteristics and plasma anti-PEG antibody carrying status in patients between the 2 groups were compared; according to anti-PEG antibody carrying status, the patients were divided into anti-PEG antibody positive group and negative group and the clinical characteristics and the incidence of hypersensitivity in patients between the 2 groups were compared. Results:A total of 12 patients were included in the study, aged from 37 to 68 years with a median age of 50 (37-68) years. Ten patients had previously used non-pegylated anthracyclines and the median cumulative dose was 329 (185, 418) mg/m 2 after a doxorubicin equivalent dose conversion. Seven patients developed hypersensitivity within 2-18 minutes after the start of infusion. Between the hypersensitivity group and the non-hypersensitivity group, differences in clinical characteristics such as age, height, weight, body surface area, previous application of anthracyclines, and the cumulative doses in patients were not significant (all P>0.05); the difference in positive rate of anti-PEG antibodies in patients was also not statistically significant (4/7 vs. 2/5, P=1.000). Among the 12 patients, 6 were positive for anti-PEG antibody and 6 were negative and the differences in the above-mentioned clinical characteristics or the incidence of hypersensitivity (3/6 vs. 4/6) in patients between the 2 groups (all P>0.05) were not significant. In the hypersensitivity group, IgE, C3, and C4 levels in serum were detected in 4 patients. Two patients with positive anti-PEG antibody had increased IgE levels (404 and 545 μg/L, respectively), 1 of which had also increased C4 level (486 mg/L); the other 2 patients with negative anti-PEG antibody had normal IgE, C3, and C4 levels. Conclusions:It has not been found that PLD-induced immediate hypersensitivity is related to the anti-PEG antibody, which may be due to the small sample size of the study. It cannot be ruled out that anti-PEG antibody may be involved in the induction of the IgE-mediated immediate hypersensitivity, which may also be mediated by complement in some patients.

MicroRNAS( miRNAs) are a class of single strand, small non-coding RNAs about 22 nucleotides, which have the function to regulate gene expression post-transcriptionally and control the biological processes,such as proliferation, differentiation and apoptosis. Recent studies indicate that miRNA plays an important role in tumor involved in invasion and metastasis. This article mainly reviews the feature of miRNA and its effect in metastasis or recurrence of breast cancer.

With the proposition of the cancer stem cell theory, researchers have separated and app-raised cancer stem cells from many malignant tumors such as leukemia, breast cancer, brain tumor, lung cancer, prostatic carcinoma and so on. Some scholars discovered that CD133+ may be a specific marker of the colon cancer,which led the fide of the colon cancer stem cell research. This paper presents the latest progress on colon cancer stern cell through its contribution on clinical drug-resistence, metastasis and application.

AIM: This study is designed to demonstrate the drug resistance breast cancer cell line MCF-7/ADM has a higher proportion of cancer stem cells than its original parent cell line MCF-7 in vitro.METHODS: Firstly,the drug resistance of MCF-7/ADM was estimated by MTT method,and then higher proportion of cancer stem cells in MCF-7/ADM than that in MCF-7 was demonstrated by three aspects: side population analysis,sphere culture and cell surface markers of breast cancer stem cells.RESULTS: The drug resistance index of MCF-7/ADM compared to MCF-7 was 37.1.The proportion of side population in MCF-7/ADM and MCF-7 was 9.60%?0.66% versus 0.39%?0.11%;The proportion of sphere-initiating cells in MCF-7/ADM and MCF-7 was 10.27%?0.64% versus 1.03%?0.15%,and the proportion of CD+44CD-24 cells in these two cell lines was 64.87%?3.87% versus 3.70%?0.53%,all are statistically significant.CONCLUSION: ADM resistance breast cancer cell line MCF-7/ADM has a higher proportion of cancer stem cells than that in its original cell line MCF-7.