Triple‑negative breast cancer (TNBC) has an aggressive phenotype and a poor outcome. The discovery that dysregulated microRNAs (miRNAs) play an important role in tumor progression has led to the suggestion that miRNAs (miRs) could be a potential target for the treatment of TNBC. In the present study, it was demonstrated that miR‑598 expression was significantly decreased in TNBC tissues and was related to the degree of lymph node metastasis of patients with TNBC. Ectopic expression of miR‑598 suppressed viability and colony formation, as well as increased the apoptosis of TNBC cells. To further understand the functional mechanism of action underlying miR‑598 in TNBC, targets of miR‑598 were predicted with the miRDB bioinformatics tool. Jagged 1 (JAG1) was identified as a direct target of miR‑598, possessing a binding site for miR‑598 in its 3'‑untranslated region. Overexpression of miR‑598 inhibited the expression of JAG1 in TNBC cells. In addition, JAG1 was highly expressed in TNBC tissues and its expression was negatively correlated with the expression of miR‑598. Overexpression of JAG1 significantly attenuated the inhibitory effects of miR‑598 on the proliferation and colony formation of TNBC cells. Collectively, these results provided novel insights into the functional mechanism of action for the miR‑598/JAG1 pathway in the development of TNBC.
Unlike other subtypes of breast cancer, triple negative breast cancer (TNBC) exhibits aggressive and metastatic behaviors and a lack of effective targeted therapeutics. (R)-9bMS, a small-molecule inhibitor of the non-receptor tyrosine kinase 2 (TNK2), significantly inhibited TNBC cell growth; however, the functional mechanism of (R)-9bMS in TNBC remains largely unknown.To explore the functional mechanism of (R)-9bMS in TNBC.Cell proliferation, apoptosis and xenograft tumor growth assays were performed to evaluate the effects of (R)-9bMS on TNBC. The expression levels of miRNA and protein were detected by RTqPCR or western blot, respectively. Protein synthesis was determined by analyzing the polysome profile and 35S-met incorporation.(R)-9bMS attenuated TNBC cell proliferation, induced cell apoptosis, and inhibited xenograft tumor growth. Mechanism study indicated that (R)-9bMS upregulated the expression of miR-4660 in TNBC cells. The expression of miR-4660 is lower in TNBC samples than that of the non-cancerous tissues. miR-4660 overexpression inhibited TNBC cell proliferation by targeting the mammalian target of rapamycin (mTOR), which reduced mTOR abundance in TNBC cells. Consistent with the downregulation of mTOR, exposure of (R)-9bMS inhibited the phosphorylation of p70S6K and 4E-BP1, which consequently interrupted the total protein synthesis and autophagy of TNBC cells.These findings uncovered the novel working mechanism of (R)-9bMS in TNBC by attenuating mTOR signaling via up-regulating miR-4660. The potential clinical significance of (R)- 9bMS in TNBC treatment is interesting to explore.
Increasing evidence has demonstrated the oncogenic roles of long non-coding RNA (lncRNA) hepatocellular carcinoma (HCC)-associated long non-coding RNA (HANR) in the development of HCC and lung cancer; however, the involvement of HANR in triple-negative breast cancer (TNBC) remains largely unknown. Our results demonstrated the significant overexpression of HANR in TNBC tissues and cells. Higher HANR levels significantly correlated with the poorer phenotypes in patients with TNBC. HANR down-regulation inhibited the proliferation and cell cycle progression and increased the apoptosis of TNBC cells. Mechanistically, immunoprecipitation-mass spectrometry revealed hexokinase II (HK2) as a direct binding target of HANR. HANR binds to and stabilizes HK2 through the proteasomal pathway. Consistent with the important role of HK2 in cancer cells, HANR depletion represses the glucose absorbance and lactate secretion, thus reprogramming the metabolism of TNBC cells. An in vivo xenograft model also demonstrated that HANR promoted tumor growth and aerobic glycolysis. This study reveals the role of HANR in modulating the glycolysis in TNBC cells by regulating HK2 stability, suggesting that HANR is a potential drug target for TNBC.
Objective
To study the efficacy of modified radical mastectomy combined with autologous skin grafting on patients with breast cancer and the effect on 1-3 years recurrence rate.
Methods
Ninety patients with breast cancer (tumor diameter≥10 cm after primary treatment or neoadjuvant therapy) were selected and divided into observation group (45 cases) and control group (45 cases) according to random number table method. Patients in control group received modified radical mastectomy of breast cancer, patients in observation group underwent modified radical mastectomy for breast cancer combined with autologous skin grafting. Efficacy, operation time, postoperative drainage time, hospital stay, postoperative complications, the recurrence rate during 1-3 years after treatment were observed and compared between the two groups.
Results
There was no significant difference in postoperative drainage time between control group and observation group(P>0.05). The operation time and hospital stay in observation group were significantly longer than those in control group (all P 0.05).
Conclusions
Modified radical mastectomy combined with autologous skin grafting in the treatment of locally advanced breast cancer, can reduce the incidence of complications, occurrence of flap necrosis in treatment and the recurrence rate, but will prolong hospital stay, which can be used as clinical reference.
Key words:
Modified radical mastectomy; Autologous skin grafting; Breast cancer; Curative effect; Recurrence rate
An ultrasensitive method of ultrasound emulsification ionic liquid microextraction (UEILME) coupled with high-performance liquid chromatography (HPLC) has been developed and introduced for the preconcentration and analysis of anthraquinone additives in cosmetic samples and five anthraquinone compounds (aloe-emodin, rhein, emodin, chrysophanol and physcion) in traditional Chinese medicines. Several parameters affecting the extraction efficiency were investigated and optimized, such as the type and amount of extraction solvent, sample pH, ultrasound time and temperature, centrifugation speed and time and ionic strength. The most favorable results were obtained using 60 mg of 1-hexyl-3-methylimidazolium hexafluorophosphate as extraction solvent. The anthraquinones were extracted from the aqueous solution (pH 2.0) by ultrasound at 40°C for 7 min and centrifuged at 2,500 rpm for 6 min. Under optimal conditions, acceptable linearity of the five anthraquinone compounds was obtained with correlation coefficients > 0.99. The limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.01 to 0.09 µg/L and 0.05 to 0.25 µg/L, respectively. The relative standard deviations (n = 3) were less than 9.8%. Moreover, the enrichment factors ranged from 80 to 197-fold. Compared with conventional dispersive liquid–liquid microextraction, the UEILME technique exhibited lower LODs and LOQs. The results demonstrated that the UEILME coupled with HPLC is a simple, environmentally friendly, sensitive and efficient method for the extraction, concentration and analysis of anthraquinone compounds.
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