Case report: A promising neoadjuvant treatment option for individuals with locally advanced HER2-positive breast cancer involves the use of Pyrotinib Maleate in combination with Trastuzumab and Pertuzumab.

Breast cancer (BC) is the prevailing malignancy among women, with HER2 overexpression observed in 20-30 % of all BC, thereby serving as a prognostic indicator for unfavorable outcomes in affected individuals. There is a necessity to establish innovative treatment protocols to expand the therapeutic alternatives accessible for managing HER2-positive BC. In this study, we report a case of HER2-positive BC that was managed in our department using a combination of three targeted drugs (Trastuzumab, Pertuzumab and Pyrotinib) along with chemotherapy. The treatment resulted in a pathological complete response (pCR) and was observed to be well-tolerated, without any significant adverse reactions. Hence, the combination of Pyrotinib and Dual HER2 blockade treatment shows promise as a neoadjuvant therapy for locally advanced HER2-positive BC to achieve a pCR in surgery. Nevertheless, this conclusion necessitates additional validation via meticulously designed clinical research investigations encompassing larger patient populations.

Long Non-coding RNA LINC01224 Promotes the Malignant Behaviors of Triple Negative Breast Cancer Cells via Regulating the miR-193a-5p/NUP210 Axis.

Triple negative breast cancer (TNBC) is a prevalent malignant tumor in women and is characterized by high incidence and mortality. Current evidence has suggested that multiple long noncoding RNAs (lncRNAs) play regulatory roles in TNBC, while the specific mechanism of LINC01224 in TNBC remains unclear. In this study, LINC01224 was highly expressed in TNBC cells. Moreover, LINC01224 downregulation inhibited TNBC cell proliferation, migration, and invasion, and promoted cell apoptosis. Additionally, LINC01224 stabilized NUP210 mRNA through interaction with miR-193a-5p, thereby aggravating the malignant phenotypes of TNBC. Overall, LINC01224 functions as a tumor promoter for TNBC.

Efficacy and safety of apatinib monotherapy for patients with advanced breast cancer: a systematic review and meta-analysis.

Background: Patients with advanced breast cancer usually have poor prognosis. Apatinib is a small-molecule tyrosine kinase inhibitor, and the reports regarding the efficacy and safety of apatinib monotherapy for advanced breast cancer in the current literature are controversial. Therefore, we performed a systematic review and meta-analysis to collect and pool efficacy and safety data of apatinib monotherapy for advanced breast cancer with the aim of providing up-to-date evidence to aid clinical practice. Methods: This study was registered at PROSPERO (CRD42020190049). Three literature databases, including PubMed, EMBASE, and Cochrane Library, were searched. For evaluating efficacy, the objective response rate and disease control rate were extracted or calculated. Safety was evaluated in terms of the proportions of patients with grade 3 or 4 treatment-related adverse events. The pooled proportions of the outcomes and their 95% confidence interval were shown. The Kaplan-Meier curves of overall survival and progression-free survival were pooled from the extracted data of the included studies. Furthermore, pooled medians for overall survival and progression-free survival were calculated. A p-value of < 0.05 was considered statistically significant. Results: Six studies were included and deemed eligible for further quality evaluation and analysis. The pooled objective response rate and disease control rate were 20.4% and 71.6%, respectively. The pooled proportions of four hematologic adverse events ranged from 2.6% to 6.9%. The pooled proportions of hypertension, hand-foot syndrome, transaminase increased, and proteinuria ranged from 4.1% to 24.3%, and other non-hematologic adverse events were <1%. The pooled median progression-free survival and overall survival were 4.00 and 10.43 months, respectively, in cases of advanced breast cancer treated with apatinib. Conclusions: This study confirms the reliable efficacy of apatinib monotherapy for advanced breast cancer. However, non-hematologic grade 3-4 adverse events, especially hypertension, are more frequently observed during apatinib treatment than during treatment with other tyrosine kinase inhibitors, such as sunitinib or sorafenib. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42020190049.

The use of trastuzumab affected by health insurance policy in Jiangsu Province of China.

BACKGROUND: Breast cancer recurrence and mortality have been shown to decrease after trastuzumab treatment in human epidermal growth factor 2 (HER2)-positive early-stage breast cancer (EBC) patients. In Jiangsu Province, trastuzumab has been subsidized for patients with HER2-positive EBC since 2013. Several studies showed that Jiangsu was one of the provinces with the highest rates of adjuvant trastuzumab therapy. To uncover the underlying reason, we designed the study to investigate trastuzumab use for HER2-positive breast cancer patients, and to examine the changes caused by medical insurance coverage for trastuzumab in Jiangsu province of China. METHODS: This was a retrospective, multicenter clinical study with follow-up data. HER2-positive EBC patients diagnosed in 7 representative hospitals in 2010, 2011, and 2013 were enrolled. Demographic and clinical data, and details of diagnosis, treatments, and prognosis, were collected. Data analysis included univariate analysis, multivariate logistic regression, survival analysis, and subgroup analysis. RESULTS: Of the 641 patients (mean age 51.01±10.79 years) included, 412 (64.27%) patients had medical insurance. Trastuzumab therapy was given to 214 (33.39%) patients. The multivariate logistic regression showed that medical insurance coverage, age, and radiotherapy were associated with trastuzumab use (P<0.05). The overall survival was significantly better in the trastuzumab group than in the non-trastuzumab group (HR: 1.607; 95% CI: 1.046-2.469; P=0.040). Subgroup analysis revealed that there was a trend towards more patients with medical insurance (P=0.073), and significantly more patients received trastuzumab therapy (P<0.001) in 2013 than in 2010-2011. Additionally, trastuzumab use in China was lower than in developed countries. Patients with medical insurance were more likely to use trastuzumab, and more patients could afford trastuzumab therapy with the development of China's health-care reform. CONCLUSIONS: Our study suggested that the percentage of patients who received trastuzumab in China was lower than developed countries. Patients who had medical insurance were more likely to use trastuzumab than those without medical insurance. The health insurance policy in China has improved access for breast cancer patients who require trastuzumab therapy.

MiR-370-5p inhibits the progression of breast cancer via targeting LUC7L3.

Breast cancer is one of the most common malignancies and one of the leading causes of cancer-induced mortality among women. Over the past decades, the occurrence of breast cancer has been a significant increase. As documented in numerous researches, microRNAs (miRNAs) play vital roles in a wide range of biological processes associated with the occurrence and development of breast cancer. Nevertheless, the role of miR-370-5p in breast cancer remains obscure, and the possible molecular regulatory mechanism needs to be further explored. In this study, our results delineated that miR-370-5p was downregulated in breast cancer tissues and cell lines. Besides, miR-370-5p overexpression suppressed cell proliferation and invasion in breast cancer. MiR-370-5p downregulation exerted an opposite result. In addition, LUC7L3 was identified as a target gene for miR-370-5p. Similar with the results induced by miR-370-5p overexpression, LUC7L3 knockdown attenuated the proliferation and invasion ability of breast cancer cells. Moreover, the alternation of LUC7L3 expression reversed the regulatory effects of miR-370-5p on cell phenotypes in breast cancer. Overall, miR-370-5p may exert antitumor effect on breast cancer. Hence, miR-370-5p may serve as a novel therapeutic marker for the treatment of patients with breast cancer.

Activation of lncRNA lnc-SLC4A1-1 induced by H3K27 acetylation promotes the development of breast cancer via activating CXCL8 and NF-kB pathway.

This study aimed to investigate the effect and potential modulation mechanism of lnc-SLC4A1-1 on breast cancer (BC) carcinogenesis. The expression of lnc-SLC4A1-1 in tissue and serum samples from BC patients, as well as BC cell lines, was detected by real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs). Next, the expression of lnc-SLC4A1-1 was silenced or upregulated in BC cells, then cell proliferation, apoptosis, migration and invasion were detected using MTT, flow cytometry analysis and Transwell assay. Meanwhile, the expression of apoptosis-related proteins and epithelial-mesenchymal transition-related proteins were detected by western blotting. Furthermore, potential mechanism of lnc-SLC4A1-1 was explored by chromatin immunoprecipitation and RNA immunoprecipitation assays. CXCL8 was overexpressed to evaluate the relationship between lnc-SLC4A1-1 and CXCL8. Lnc-SLC4A1-1 was significantly up-regulated in BC tissue, serum samples and cell lines. In BC cells, lnc-SLC4A1-1 knockdown promoted cell apoptosis and suppressed cell proliferation, migration and invasion. Furthermore, lnc-SLC4A1-1 is transcriptionally activated by H3K27 acetylation, and lnc-SLC4A1-1 interacted with transcription factor (NF)-κB p65, thereby regulating CXCL8 expression. Meanwhile, CXCL8 overexpression partly reversed the effects of lnc-SLC4A1-1 knockdown on cell viability, apoptosis, migration and invasion in BC cells. Lnc-SLC4A1-1 could promote the development of BC by regulating NF-κB/CXCL8. Highlights Lnc-SLC4A1-1 was overexpressed in BC tissues, blood and cell lines. Lnc-SLC4A1-1 was transcriptionally activated by H3K27 acetylation. Lnc-SLC4A1-1 interacted with NF-κB to promote CXCL8 expression. Lnc-SLC4A1-1 could promote the development of BC.

MicroRNA-1270 modulates papillary thyroid cancer cell development by regulating SCAI.

PURPOSE: We intended to evaluate expression and mechanisms of human microRNA 1270 (hsa-miR-1270) in papillary thyroid cancer (PTC). METHODS: In PTC cell lines and human PTC tumors, hsa-miR-1270 expressions were evaluated by qRT-PCR. Hsa-miR-1270 was downregulated in TPC1 and K1 cells via lentiviral transduction. Its effects on PTC cancer cell proliferation, migration and in vivo transplantation were assessed, respectively. Potential targeting of hsa-miR-1270 on downstream gene, Suppressor Of Cancer Cell Invasion (SCAI), was assessed. In hsa-miR-1270-downregulated PTC cells, SCAI was further downregulated to examine its associating role in hsa-miR-1270-mediated regulation on cancer cell proliferation and migration. RESULTS: Hsa-miR-1270 was aberrantly upregulated in PTC cell lines and human PTC tumors. In TPC1 and K1 cells, lentivirus-mediated hsa-miR-1270 downregulation suppressed cancer cell proliferation, migration and in vivo transplantation. Hsa-miR-1270 binds SCAI and inversely regulated SCAI gene expression in PTC cells. SCAI downregulation removed the suppressing effects of hsa-miR-1270 downregulation in human PTC cells. CONCLUSION: Hsa-miR-1270 downregulation may suppress human PTC cell development both in vitro and in vivo. The regulatory mechanism of hsa-miR-1270 in PTC may be primarily associated with SCAI.

Enhancement radiosensitization of breast cancer cells by deguelin.

OBJECTIVE: Radiation can activate the phosphatidylinositol 3-kinase/Akt pathway and cannot downregulate survivin expression in breast cancer cells. Deguelin induces apoptosis in breast cancer cells by inhibiting pAkt and survivin expression. In this study, we assessed the effect of deguelin on radiosensitization of human breast cancer cells and its possible mechanism. METHODS: Deguelin and radiation were administrated in MDA-MB-231 human breast cancer cells. The cytotoxic interactions and mutual influences between these 2 modalities were analyzed by a series of assays including clonogenic, flow cytometric, and Western blotting. RESULTS: Phospho-Akt expression and survivin expression significantly decreased after 10 nM deguelin treatment, while phospho-Akt expression increased and survivin expression did not alter after radiation (3 Gy). However, phospho-Akt expression and survivin expression further significantly decreased after deguelin combined with radiation treatment. Deguelin combined with radiation markedly decreased clonogenic cell survival. After treatment of deguelin (10 nM) combined with radiation (3 Gy), caspase-dependent apoptosis was significantly increased and cell cycle was arrested in the G2-M phase in MDA-MB-231 cells. CONCLUSIONS: Deguelin attenuates radiation-induced prosurvival Akt signaling and enhances the radiosensitivity of MDA-MB-231 cells, and the mechanisms for this action may include inhibiting phospho-Akt and survivin expression, increasing caspase-dependent apoptosis, and prolonging cell cycle arrest in the G2-M phase.

Suspension culture combined with chemotherapeutic agents for sorting of breast cancer stem cells.

BACKGROUND: Cancer stem cell (CSC) hypothesis has not been well demonstrated by the lack of the most convincing evidence concerning a single cell capable of giving rise to a tumor. The scarcity in quantity and improper approaches for isolation and purification of CSCs have become the major obstacles for great development in CSCs. Here we adopted suspension culture combined with anticancer regimens as a strategy for screening breast cancer stem cells (BrCSCs). BrCSCs could survive and be highly enriched in non-adherent suspension culture while chemotherapeutic agents could destroy most rapidly dividing cancer cells and spare relatively quiescent BrCSCs. METHODS: TM40D murine breast cancer cells were cultured in serum-free medium. The expression of CD44+CD24- was measured by flow cytometry. Cells of passage 10 were treated in combination with anticancer agents pacilitaxel and epirubicin at different peak plasma concentrations for 24 hours, and then maintained under suspension culture. The rate of apoptosis was examined by flow cytometry with Annexin-V fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining method. Selected cells in different amounts were injected subcutaneously into BALB/C mice to observe tumor formation. RESULTS: Cells of passage 10 in suspension culture had the highest percentage of CD44+CD24- (about 77 percent). A single tumor cell in 0.35 PPC could generate tumors in 3 of 20 BALB/C mice. CONCLUSION: Suspension culture combined with anticancer regimens provides an effective means of isolating, culturing and purifying BrCSCs.

Suspension culture combined with anticancer regimens for screening breast cancer stem cells.

Breast cancer stem cells (BrCSCs)have been first identified in solid tumors. To be more exact, they are defined as tumorigenic cancer cells which exhibit the capacity to form tumors distinct from the majority non-tumorigenic cancer cells. However it is only a minor subset that cancer stem cells are highly enriched in. It is still unknown how to find the definitive research subject - "a single breast cancer stem cell" - that can cause a new tumor by itself. Since recent studies suggest that BrCSCs have a higher proportion in suspension culture and have a greater resistance to chemotherapy regimens, we propose a novel strategy to isolate and identify BrCSCs:suspension culture combined with anticancer regimens. This double sorting method by means of the unique properties of BrCSCs may be helpful to screen genuine cancer stem cells(CSCs).

Caspase-8 in apoptosis of hepatoma cell induced by 5-fluorouracil.

OBJECTIVE: To explore the relationship between the changes in the activity of caspase-8 and apoptosis of HepG2 cells induced by 5-fluorouracil (5-Fu). METHODS: Human hepatoma HepG2 cells were treated with 5-Fu at the concentrations of 1X10(-1), 1X10(-2), 1X10(-3), 1X10(-4), 1X10(-5) mol/L and for 1, 2, 4, 8, 16, 24 hours, respectively. The caspase-8 activity was detected using caspase-8 fluorescent assay kit. The apoptotic rate of HepG2 cells induced by 5-Fu with or without the caspase-8 inhibitor IETD-FMK was measured by flow cytometry. RESULTS: After the HepG2 cells were treated with 10(-2) mol/L 5-Fu, the caspase-8 activity increased gradually and reached the peak level (313.9+/-6.9) at 16 hours, then fell down. Compared with the control group, the activity was still significantly higher (274.2+/-3.9 vs 68.3+/-3.6, P<0.01). With the increasing concentration of 5-Fu, the caspase-8 activity was also increased; the activity in high concentration 5-Fu was significantly higher than that in low concentration 5-Fu (370.5+/-4.7 vs 313.7+/-6.9; 225.7+/-5.4 vs 183.3+/-4.8; 183.3+/-4.8 vs 124.0+/-6.2, P<0.01). The caspase-8 activity was the highest at 1X10(-1) mol/L 5-Fu (370.5+/-4.7). The caspase-8 activity in low concentration 5-Fu was higher than in the blank control group and inhibitor group (124.0+/-6.2 vs 68.5+/-3.4; 124.0+/-6.2 vs 41.0+/-2.1, P<0.01). IETD-FMK could block the activation of caspase-8 and reduce the apoptosis of HepG2 cells induced by 5-Fu. The apoptotic rate of HepG2 cells in the 5-Fu group was significantly different from that in the inhibitor group (P<0.01). CONCLUSIONS: 5-Fu can induce apoptosis of HepG2 cells via caspase-8 signal transduction pathway, which can be blocked by IETD-FMK. 5-Fu promotes the increase of caspase-8 activity in a time- or concentration-dependent manner.