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As a critical catalytic subunit of N6-methyladenosine (m6A) modification in messenger RNA, ALKBH5 has been reported to affect the progression of numerous tumors. However, the functions and mechanisms of ALKBH5 in thyroid cancer remain largely unknown. Relative mRNA and protein levels in thyroid cancer tissues and cells were detected by qRT-PCR and western blot, respectively. The proliferation and viability were evaluated using colony formation and CCK-8 assays. Intracellular iron level was measured by an iron colorimetric assay kit. ROS level was determined using CellRox Green reagent. TIAM1 mRNA m6A level was detected by MeRIP. Xenograft tumor growth was performed to examine the role of ALKBH5 in thyroid tumor growth in vivo. ALKBH5 was decreased in thyroid cancer tissues and cells. ALKBH5 overexpression inhibited thyroid cancer cell proliferation and increased the levels of Fe

Introduction Triple-negative breast cancer (TNBC) is currently the most malignant subtype of breast cancer without effective targeted therapies. DNAJB4 (Dnaj heat shock protein family (Hsp40) member B4) is a member of the human heat shock protein family (Hsp40). The clinical significance of DNAJB4 in breast cancer has been reported in our previous study. However, the biological function of DNAJB4 in TNBC cell apoptosis remains unclear to date. Methods The expression of DNAJB4 in normal breast cells, breast cancer cells, four-paired TNBC tissues, and adjacent noncancerous tissues was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay. The role of DNAJB4 in TNBC cell apoptosis was investigated using a number of gain- and loss-of-function in vitro and in vivo assays. The underlying molecular mechanisms in TNBC cell apoptosis were elucidated via Western blot assay. Results DNAJB4 expression was significantly downregulated in TNBC tissues and cell lines. DNAJB4 knockdown inhibited TNBC cell apoptosis and promoted tumorigenicity in vitro and in vivo, but DNAJB4 overexpression resulted in the opposite. Mechanically, DNAJB4 knockdown inhibited TNBC cell apoptosis through suppression of the Hippo signaling pathway, and the result was reversed after DNAJB4 overexpression. Conclusions DNAJB4 promotes TNBC cell apoptosis by activating the Hippo signaling pathway. Therefore, DNAJB4 may act as a prognostic biomarker and therapeutic target for TNBC.

IntroductionCancer stem cells (CSCs) targeted therapy holds the potential for improving cancer management; identification of stemness-related genes in CSCs is necessary for its development.MethodsThe Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets were used for survival analysis. ZSCAN1 correlated genes was identified by Spearman correlation analysis. Breast cancer stem-like cells (BCSLCs) were isolated by sorting CD44+CD24- cells from suspension cultured breast cancer (BC) spheroids. The sphere-forming capacity and sphere- and tumor-initiating capacities were determined by sphere formation and limiting dilution assays. The relative gene expression was determined by qRT-PCR, western blot. Lentivirus system was used for gene manipulation. Nuclear run-on assay was employed to examine the levels of nascent mRNAs. DNA pull-down and Chromatin immunoprecipitation (ChIP) assays were used for determining the interaction between protein and target DNA fragments. Luciferase reporter assay was used for evaluating the activity of the promoter.Results and discussionZSCAN1 is aberrantly suppressed in BC, and this suppression indicates a bad prognosis. Ectopic expression of ZSCAN1 inhibited the proliferation, clonogenicity, and tumorigenicity of BC cells. ZSCAN1-overexpressing BCSLCs exhibited weakened stemness properties. Normal human mammary epithelial (HMLE) cells with ZSCAN1 depletion exhibited enhanced stemness properties. Mechanistic studies showed that ZSCAN1 directly binds to -951 ~ -925bp region of WWTR1 (encodes TAZ) promoter, inhibits WWTR1 transcription, thereby inhibiting the stemness of BCSCs. Our work thus revealed ZSCAN1 as a novel stemness-related tumor suppressor and transcriptional repressor in BC.

Cisplatin is an effective chemotherapeutic agent in facilitating the inhibition of proliferation, migration, and invasion in cancerous cells. However, the detailed mechanism of the regulation by cisplatin of human breast cancer cells is still unclear. This study aimed to investigate the mechanism of kruppel-like factor 2 (KLF2) transcription factor in cisplatin therapy for breast cancer. RT-qPCR was performed to quantify the expression of KLF2 and WEE1 in clinical tissue samples from breast cancer patients and in MDA-MB-231 cells. ChIP assay and dual-luciferase reporter assay were used to analyze the potential-binding sites of KLF2 and WEE1 promoter. Gain- or loss-of-function approaches were used to manipulate KLF2 and WEE1 in cisplatin-treated MDA-MB-231 cells, and the mechanism of KLF2 in breast cancer was evaluated both via CCK-8 assay, flow cytometry, Transwell assay, and Western blot. Further validation of the KLF2 was performed on nude mouse models. Breast cancer tissues and cells showed a relative decline of KLF2 expression and abundant WEE1 expression. Cisplatin inhibited the proliferation, migration, and invasion of MDA-MB-231 cells. Overexpression of KLF2 enhanced the inhibitory effect of cisplatin on the malignant characteristics of MDA-MB-231 cells in vitro. KLF2 targeted WEE1 and negatively regulated its expression, thus enhancing the sensitivity to cisplatin of breast cancer cells as well as tumor-bearing mice. Overall, these results suggest that KLF2 can potentially inhibit WEE1 expression and sensitize breast cancer cells to cisplatin, thus presenting a promising adjunct treatment.

The combination of chemo-photothermal therapy has a wide application prospect in the intensive treatment of cancer. In this study, we developed a complex nanoparticle consist of polypyrrole, cystine dihydrochloride and hyaluronan. The polypyrrole nanoparticles loaded with paclitaxel exhibited good photothermal effects, and the drug release can be triggered by combined response of temperature and redox. In vitro biological studies indicated the nanoparticles could effectively induced apoptosis of MDA-MB-231 breast cancer cells involved in the potential mechanism of inhibition of biological expression of heat shock proteins and JAK-STAT signaling pathway. In addition, the nanoparticles have a significant inhibitory effect on cancer growth in breast tumor-bearing mice model, indicating that they have great potential for synergistic chemo-photothermal therapy.

This study reports that the novel binary g-C3N4@NiFe-LDH heterostructured photocatalysts were simply prepared by loading well-dispersed g-C3N4 nanosheets on the surface of NiFe-LDH precursor via the hydrothermal synthesis process. The morphologic structure, chemical composition and optical properties of the as-prepared nanocomposites were clearly characterized by using XRD, SEM, FT-IR, UV–Vis DRS, XPS and N2 adsorption–desorption techniques. In the photocatalytical degradation experiments, it can be seen that the optimal g-C3N4@NiFe-LDH nanocomposites can achieve the highest degradation efficiency (99%) for rhodamine B (RhB) within 240 min under visible light irradiation, and the corresponding pseudo-first-order rated constant is 0.912 h−1. The improvement of photocatalytical performance can be attributed to the enhanced visible light absorption and fast separation of the photo-generated electron–hole pairs. Besides, the degradation efficiency can still remain more than 80% via four cycle processes, demonstrating its remarkable stability and reusability. More importantly, a possible Z-scheme photocatalytic mechanism was proposed according to the analysis of energy band structure and the radicals trapping experiments. This study will be beneficial for the design and research of Z-scheme g-C3N4-based heterojunction photocatalysts in the environmental remediation field.

Accumulating evidence has suggested that long noncoding RNAs (lncRNAs) exert crucial modulation roles in the biological behaviors of multiple malignancies. Nonetheless, the specific function of lncRNA LINC00284 in papillary thyroid cancer (PTC) remains not fully understood. The objective of this research was to explore the influence of LINC00284 in PTC and elucidate its potential mechanism. The Cancer Genome Atlas (TCGA), gene expression omnibus (GEO) datasets were used to analyze LINC00284 expression differences in thyroid cancer and normal samples, followed by the verification of qRT-PCR in our own PTC and adjacent non-tumor tissues. The impacts of LINC00284 on PTC cell growth were detected in vitro via CCK-8, colony formation, EdU assays, and in vivo via a xenograft tumor model. Bioinformatics analyses and biological experiments were conducted to illuminate the molecular mechanism. We found that LINC00284 expression was remarkably increased in PTC tissues and its overexpression was closely correlated with larger tumor size. In addition, silencing LINC00284 could effectively attenuate PTC cell proliferation, induce apoptosis and G1 arrest in vitro, as well as suppress tumorigenesis in mouse xenografts. Mechanistic investigations showed that LINC00284 acted as a competing endogenous RNA (ceRNA) for miR-3127-5p, thus resulting in the disinhibition of its endogenous target E2F7. In short, our findings indicated that LINC00284–miR-3127-5p–E2F7 axis exerted oncogenic properties in PTC and may offer a new promising target for the diagnosis and therapy of PTC.

Backgrounds: Triple-negative breast cancer (TNBC) is considered to be the most malignant subtype of breast cancer (BC). Heparanase (HPSE) has been reported to contribute to tumor development, but its potential function in TNBC is not clear. The intention of this study was to investigate whether HPSE affects TNBC progression and to explore the possible mechanisms. Methods: Bioinformatics analyses were applied to analyze the expression of HPSE in TNBC samples and normal breast samples. The mRNA and protein levels of HPSE in TNBC cells were detected by RT-qPCR and western blot. Function assays, including CCK-8 assay, colony formation assay, transwell assay and wound healing assay were conducted to validate the effects of HPSE silencing on TNBC cell proliferation and migration. Mechanism experiments were performed to explore the upstream molecular mechanism of HPSE in TNBC cells. Results: Silencing of HPSE suppressed the proliferation and migration of TNBC cells. Moreover, hypoxia inducible factor-1 alpha (HIF-1α) interacted with HPSE promoter and promoted the transcription of HPSE. Isoproterenol (ISO), a pharmacological substitute for chronic stress-induced sympathetic activation, was proven to induce HIF-1α upregulation, so as to transcriptionally activate HPSE in TNBC cells. Furthermore, it manifested that ISO facilitated TNBC cell proliferation and migration in a HPSE-dependent way. Conclusion: HPSE activated by ISO-induced HIF-1α promoted TNBC cell proliferation and migration, which might offer a novel sight for TNBC treatment.

A number of kinesin proteins (KIFs) have been implicated in the development of multiple cancers. However, little is known about the expression and function of KIF15 in human breast cancer. Herein, we detected KIF15 expression in breast cancer tissues and paired adjacent normal tissues using immunohistochemistry and quantitative real-time polymerase chain reaction analysis, and the correlation of KIF15 expression with clinicopathological parameters was evaluated statistically. The role of KIF15 in cell proliferation, migration, tumor growth and metastasis of breast cancer cells was investigated in vitro and in vivo, and we explored potential molecular mechanisms underlying the effects of KIF15 in breast cancer through western blot analysis. The results revealed that increased KIF15 expression in breast cancer tissues were positively related with tumor size, lymph node metastasis and TNM stage, and higher KIF15 expression predicts a worse prognosis of patients with breast cancer. Furthermore, KIF15 knockdown markedly attenuated breast cancer cell proliferation, migration, tumor growth and metastasis in vitro and in vivo, and silenced KIF15 expression significantly inhibited the expression of phosphorylated AKT, phosphorylated JNK, and cyclin D1, while both p53 and p21 protein expressions were strongly enhanced. These results suggest that KIF15 is a potential oncogene in human breast cancer.

PURPOSE Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) includes a taxane and an anthracycline. Concomitant capecitabine may be beneficial, but robust data to support this are lacking. The efficacy and safety of the addition of capecitabine into the TNBC adjuvant treatment regimen was evaluated. PATIENTS AND METHODS This randomized, open-label, phase III trial was conducted in China. Eligible female patients with early TNBC after definitive surgery were randomly assigned (1:1) to either capecitabine (3 cycles of capecitabine and docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide) or control treatment (3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide). Randomization was centralized without stratification. The primary end point was disease-free survival (DFS). RESULTS Between June 2012 and December 2013, 636 patients with TNBC were screened, and 585 were randomly assigned to treatment (control, 288; capecitabine, 297). Median follow-up was 67 months. The 5-year DFS rate was higher for capecitabine than for control treatment (86.3% v 80.4%; hazard ratio, 0.66; 95% CI, 0.44 to 0.99; P = .044). Five-year overall survival rates were numerically higher but not significantly improved (capecitabine, 93.3%; control, 90.7%). Overall, 39.1% of patients had capecitabine dose reductions, and 8.4% reported grade ≥ 3 hand-foot syndrome. The most common grade ≥ 3 hematologic toxicities were neutropenia (capecitabine, 136 [45.8%]; control, 118 [41.0%]) and febrile neutropenia (capecitabine, 50 [16.8%]; control, 46 [16.0%]). Safety data were similar to the known capecitabine safety profile and generally comparable between arms. CONCLUSION Capecitabine when added to 3 cycles of docetaxel followed by 3 cycles of a 3-drug anthracycline combination containing capecitabine instead of fluorouracil significantly improved DFS in TNBC without new safety concerns.

Background: The present study focused on the effects of dual-targeting MiR-4282 and ABCC4 on drug resistance of breast cancer cells and the molecular mechanisms, expecting to provide a new approach for treating drug-resistant breast cancer. Material and methods: MiR-4282 overexpression and ABCC4 interference double gene lentiviral vectors were constructed. CCK-8, flow cytometry, Transwell assay and scratch assay were used to determine the overexpression of A and B Group, as well as the expression, proliferation, apoptosis, invasion and migration of C and D Group cells respectively. CCK-8 assay was applied to detect doxorubicin sensitivity. WB was used to detect the expressions of ABCC4, p53 and P-gp proteins in each group. Results: Overexpression of MiR4282 and downregulation of ABCC4 expression inhibited proliferation, invasion and migration of the cells, impeded normal cell cycle progression, and promoted apoptosis of the cells. The effect of dual-targeting MiR-4282 and ABCC4 on cell function is more pronounced. The results of CCK-8 assay showed that overexpression of MiR-4282 and downregulation of ABCC4 expression significantly promoted the sensitivity of MCF-7-ADR to doxorubicin, and dual-targeting MiR-4282 and ABCC4 were sensitive to the cell. The promotion effect is more obvious. WB analysis showed that overexpression of MiR-4282 and downregulation of ABCC4 expression significantly inhibited p53 protein in the cells, plus the inhibitory effects of dual-targeting MiR-4282 and ABCC4 were more obvious. MiR-4282 overexpression could prominently inhibit P-gp protein expression in the cells. Conclusion: Overexpression of MiR-4282 and downregulation of ABCC4 expression inhibit the proliferation, invasion and migration of MCF-7-ADR.

Background: Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) comprises a taxane and an anthracycline. Concomitant capecitabine may add efficacy benefits, but robust data are lacking. The efficacy and safety of capecitabine integration into the TNBC adjuvant treatment regimen was evaluated. Methods: This was a randomised, open-label, phase 3 trial conducted in China (ClinicalTrials.gov identification NCT01642771). Post-resection, eligible female patients with early TNBC were randomly assigned (1:1) to either capecitabine treatment (3 cycles of capecitabine and docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine [TX-XEC]), or control treatment (3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil [T-FEC]). Randomisation was centralised without stratification. The primary endpoint was 5-year disease-free survival (DFS). Findings: Between June 2012 and November 2013, 585 patients were randomized to treatment (capecitabine, n=297; control, n=288), of whom 561 were treated per protocol (n=288 and n=273, respectively). Median follow-up was 67 months. The 5-year DFS rate was longer with capecitabine than with control treatment (86·26% vs. 80·23%, hazard ratio 0·66, 95% confidence intervals 0·44-0·98; p=0·038). The 5-year overall survival rates were similar (93·27% vs. 90·55%, respectively). Overall, 38·89% patients had capecitabine dose reductions and 8·42% reported grade 3/4 hand-foot syndrome. The most common grade 3/4 hematologic toxicities were neutropenia (capecitabine 136 [45·79%] patients vs. control 119 [41·32%] patients) and febrile neutropenia (49 [16·5%] vs. 46 [15·97%] patients). Safety data were in line with the known capecitabine safety profile and generally comparable between arms. Interpretation: Capecitabine, when administered concomitantly with standard adjuvant taxane/anthracycline chemotherapy, significantly improved DFS rates in TNBC, with no new safety concerns. Table 1: Baseline patient demographics and clinical characteristics (PPS population; n=561)T-FEC (n=273)TX-XEC (n=288)pAge (years), mean ± SD48.30 ± 8.7649.07 ± 10.440·3501BSA (m2), mean ± SD1.60 ± 0.111.60 ± 0.110·4209Menstruation0·2946Premenopausal61·5757·09Postmenopausal38·4342·91Family History26·3726·830·9029Operation TypeBreast conserving21·8525·090·3683Mastectomy78·1574·91SLNB28·5226·130·5275Axillary dissection71·4873·87Node Stage0·5967N065·0665·97N123·7925·35N26·323·82N34·834·86T Stage0·2938T1a,b4·172·33T1c42·5041·25T250·4255·25T32·921·17Histology0·7190IDC89·6390·24ILC0·741·39Other9·638·36Grade0·2322I3·832·94II47·6640·76III48·5156·30Ki67 ≥30%+87·2185·770·6245LVI +14·8110·100·1363Surgery-to-chemo time (days), mean ± SD16·94 ± 7·7717·99 ± 9·240·1581Data are % except where specified.BSA=body surface area; IDC=invasive ductal carcinoma; ILC=invasive lobular carcinoma; LVI=lymphovascular invasion; PPS=per protocol set; SD=standard deviation;Table 2: Number of events (PPS population; n=561)T-FECTX-XEC(n=273)(n=288)Any event57 (20·88)41 (14·24)Second primary4 (1·47)5 (1·74)Contralateral breast5 (1·83)6 (2·08)Local recurrence18 (6·59)7 (2·43)Ipsilateral breast/Chest135Regional lymph nodes83Distant recurrence37 (13·55)29 (10·07)Liver37Lung1714Bone67Other2714Death26 (9·52)19 (6·60) Citation Format: Junjie Li, Keda Yu, Da Pang, Changqin Wang, Jun Jiang, Suisheng Yang, Yunjiang Liu, Peifen Fu, Yuan Sheng, Guojun Zhang, Yali Cao, Qi He, Shude Cui, Xijing Wang, Guosheng Ren, Xinzheng Li, Shiyou Yu, Pengxi Liu, Jinhai Tang, Ouchen Wang, Zhimin Fan, Guoqin Jiang, Jin Zhang, Zhimin Shao, Chinese Breast Cancer Study Group (CBCSG) 010. Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for triple-negative breast cancer (cbcsg010): An open-label, randomised, multicentre, phase 3 trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS1-08.

Background: No consensus has been reached on the best surgical approach for secondary hyperparathyroidism. We evaluated the short-term and long-term efficacy and safety of total parathyroidectomy with autotransplantation (TPTX+AT) and subtotal parathyroidectomy (SPTX).Methods: We retrospectively analyzed the data of 259 patients undergoing TPTX+AT or SPTX between 2010 and 2021 in the Second Affiliated Hospital of Soochow University, and carried out follow-up. We compared the differences in symptoms, serological examinations, complications and mortalities between the two groups, and explored the risk factors of poor prognosis, death and recurrence.Results: Of the 259 patients, 208 underwent TPTX+AT and 51 underwent SPTX. The postoperative day 1 serum intact PTH level was higher in TPTX+AT group than that in SPTX group (P=.023). The risk of all-cause mortality in TPTX+AT group was lower (P =. 018), and recurrent PTX was more common in TPTX+AT group (P =. 011). The risk of recurrence was similar. There was no significant difference in the incidence of most complications including hematoma, recurrent laryngeal nerve injury, wound infection, adverse cardiovascular outcomes, fracture and permanent hypoparathyroidism between two groups. Results from Cox regression showed the SPTX operation approach (HR 3.53, P = 0.021) and older age (HR 1.06, P = 0.035) were risk factors of all-cause mortality.Conclusion: Due to the lower risk of death after TPTX+AT and the low renal transplantation rate, we prefer TPTX+AT to treat most Chinese population with secondary hyperparathyroidism.

Background Ferroptosis is a novel iron‐dependent form of cell death, which is implicated in various diseases including cancers. However, the influence of ferroptosis‐related genes on the prognosis of breast cancer remains unclear. Methods RNA sequencing data of 1053 breast cancer tissue samples and 111 normal tissue samples from The Cancer Genome Atlas (TCGA) were analyzed. Expression levels of 259 ferroptosis‐related genes were compared. Gene Ontology (GO) and the Kyoto Gene and Genomic Encyclopedia (KEGG) analyses were conducted on differentially expressed genes. Cox univariate analysis was conducted to explore the potential prognostic biomarkers of breast cancer. Infiltrating immune cell status was assessed. Results A total of 66 ferroptosis‐related genes were differentially expressed in breast cancer tissues. The enriched GO terms included Biological Process (mainly included response to oxidative stress, cellular response to chemical stress, multicellular organismal homeostasis, cofactor metabolic process, response to metal ion, response to steroid hormone, cellular response to oxidative stress, transition metal ion homeostasis, iron ion homeostasis, and cellular iron ion homeostasis), Cellular Component (mainly included apical plasma membrane, early endosome, apical part of cell, lipid droplet, basolateral plasma membrane, blood microparticle, clathrin‐coated pit, caveola, astrocyte projection, and pronucleus) and Molecular Function (mainly included iron ion binding, ubiquitin protein ligase binding, oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, oxidoreductase activity, acting on the CH−OH group of donors, NAD or NADP as acceptor, ferric iron binding, aldo−keto reductase (NADP) activity, oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, steroid dehydrogenase activity, alditol:NADP+1−oxidoreductase activity, and alcohol dehydrogenase (NADP+) activity). The enriched KEGG pathway mainly included the HIF‐1 signaling pathway, NOD‐like receptor signaling pathway, ferroptosis, IL‐17 signaling pathway, central carbon metabolism in cancer, PPAR signaling pathway, PD‐L1 expression, and PD‐1 checkpoint pathway in cancer. Among them, 38 ferroptosis‐related genes were significantly associated with the prognosis of breast cancer. The prognostic model was constructed, and breast cancer patients in low‐risk group had a better prognosis. In addition, risk score of ferroptosis prognostic model was negatively correlated with B cells (r = −0.063, p = 0.049), CD8+ T cells (r = −0.083, p = 0.010), CD4+ T cells (r = −0.097, p = 0.002), neutrophils (r = −0.068, p = 0.033), and dendritic cells (r = 0.088, p = 0.006). Conclusions The ferroptosis pathway plays a key role in breast cancer. Some differentially expressed ferroptosis‐related genes can be used as prognostic biomarkers for breast cancer., A: A forest plot of Cox univariate analysis. B: A forest plot of Cox multivariate analysis. C: Survival‐dependent receiver operating characteristic curves for risk score, age, tumor size, and lymph node statue and metastasis statue.

Qin Li,1,* Jie Ren,2,* Wei Liu,3 Guoqin Jiang,2 Rongkuan Hu1 1GenePharma Co., Ltd., Suzhou, 215125, Jiangsu, People’s Republic of China; 2Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoqin JiangDepartment of General Surgery, The Second Affiliated Hospital, Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu, People’s Republic of ChinaTel +86-512-67784797Email jiang_guoqin@163.comRongkuan HuGenePharma Co., Ltd., 199 Dongping Street, Suzhou, 215125, Jiangsu, People’s Republic of ChinaTel +86-512-86668828Email rkhu@mail.ustc.edu.cnPurpose: The purpose of our research was to identify and evaluate synthetic phosphorothioate-modified CPG oligodeoxynucleotides (CPG-ODNs) activating innate and adaptive immune responses. Furthermore, combined treatment with CpG and an mRNA cancer vaccine was evaluated in melanoma models as a therapeutic approach.Methods: A molecular assay was used to screen new CpG molecules; mouse modeling and pathological analysis were used to confirm the antitumor effect of CpG alone or in combination with an mRNA vaccine. Finally, safety was assessed by monitoring blood biochemistry.Results: We first screened and identified a new CpG-B class ODN (CpG2018B) that effectively stimulated type II interferons in both mouse plasmacytoid dendritic cells (pDCs) and human peripheral blood mononuclear cells (PBMCs). In addition, CpG2018B promoted cytokine production mainly via toll-like receptor 9 (TLR9) pathways. We further demonstrated that intratumoral (IT) injection of CpG2018B inhibited melanoma growth in syngeneic models and could turn “cold” tumors into “hot” tumors. Then, CpG2018B and an mRNA-based neoantigen cancer vaccine were encapsulated in lipid nanoparticles (LNPs) and intratumorally injected into melanoma mouse models. Interestingly, vaccination with CpG or the mRNA vaccine alone could inhibit tumor growth, while combination of CpG with the mRNA vaccine enhanced the antitumor effect. Finally, we described the long-term safety and tolerability of CpG2018B and mRNA therapy in mice model.Conclusion: We identified a novel CpG-B class ODN to promote the immune response, and CpG combined with mRNA cancer vaccines is an attractive candidate approach for immunostimulatory sequence (ISS)-based therapeutic strategies.Keywords: CpG, IFN-γ, TLR9, mRNA vaccine, neoantigen

Objective To determine the feasibility and efficacy of breast reconstruction with silicone prosthesis immediately following polyacrylamide gel removal. Study design An observational study. Place and duration of study Department of Breast and Thyroid Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China, from November 2013 to May 2017. Methodology Twenty-seven patients with serious complications resulting from polyacrylamide gel (PAAG) injection were operated in our hospital. Using an inframammary fold incision, the PAAG and surrounding tissues were completely removed. All patients were received mastopexy and immediate breast reconstruction. Results Of all patients, 26 reported relief of preoperative complications, without obvious postoperative complications. Only one patient developed recurring infections after surgery and removed the prostheses. Conclusion After removal of PAAG, mastopexy followed by immediate breast reconstruction allows the patient to obtain a satisfactory appearance without serious complications. The key to successful breast reconstruction with prostheses first lies with the complete excision of PAAG and surrounding tissues.

Two ATP-binding cassette transporters, ABCB1/MDR1 and ABCG2/BCRP, are considered the most critical determinants for chemoresistance in hepatocellular carcinoma. However, their roles in the chemoresistance in liver cancer stem cells remain elusive. Here we explored the role of inhibition of MDR1 or ABCG2 in sensitizing liver cancer stem cells to doxorubicin, the most frequently used chemotherapeutic agent in treating liver cancer. We show that the inhibition of MDR1 or ABCG2 in Huh7 and PLC/PRF/5 cells using either pharmacological inhibitors or RNAi resulted in the elevated level of intracellular concentration of doxorubicin and the accompanied increased apoptosis as determined by confocal microscopy, high-performance liquid chromatography, flow cytometry, and annexin V assay. Notably, the inhibition of MDR1 or ABCG2 led to the reversal of the chemoresistance, as evident from the enhanced death of the chemoresistant liver cancer stem cells in tumorsphere-forming assays. Thus, the elevation of effective intracellular concentration of doxorubicin via the inhibition of MDR1 or ABCG2 represents a promising future strategy that transforms doxorubicin from a traditional chemotherapy agent into a robust killer of liver cancer stem cells for patients undergoing transarterial chemoembolization.

Objective: To investigate the function of IncRNA-TMPO-AS1 in breast cancer (BC) and to further explore its molecular mechanism. Methods: TMPO-AS1, miR-4731-5p and FOXM1 were quantitatively determined using qRT-PCR. CCK-8 assays, plate cloning experiments, wound healing and Transwell assays, and flow cytometry were used to assess the biological behaviors of BC cells. Dual-luciferase reporter assays were used to assess the interactions between TMPO-AS1 and its downstream targets. The apoptosis and cell cycle-related proteins were quantitatively determined using Western blot. Results: In the BC tissues and cells, TMPO-AS1 was significantly increased (P

Synthetic phosphorthiolate modified CPG-oligodeoxynucleotides (CPG-ODN) activate innate and adaptive immune responses, which being exploited as a therapeutic approach. Here, we first screened and identified a new CpG-B class ODN (CpG2018B) that effectively stimulates type II interferon both in mouse Plasmacytoid dendritic cells (p-DC) and human PBMC. In addition, CpG2018B promotes cytokine production mainly via toll-like receptor 9 (TLR9) pathways. We further demonstrated that intratumoral (IT) injection of CpG2018B inhibits melanoma growth in syngeneic models and could turn “cold” tumors into “hot” tumors. Then, CpG2018B and mRNA based neo-antigen cancer vaccine were encapsulated into lipid-nanoparticle (LNP) and intratumoral injected into melanoma mice models. Interestingly, vaccination with CpG or mRNA vaccine alone could inhibit tumor growth respectively, while, CpG combine with mRNA vaccine enhanced the anti-tumor effect. At last, we described the long-term safety and tolerability of CpG2018B and mRNA therapy in mice models. In conclusion, we identified a novel CpG-B ODNs to promote immune response and CpG combine with mRNA cancer vaccines are attractive candidate for immune stimulatory sequences (ISS) based therapeutic strategies.

Objective. To study the expression of programmed cell death ligand-1 (PD-L1) and breast cancer susceptibility gene 1 (BRCA1) in triple-negative breast cancer (TNBC) patients and analyze their relationship with clinicopathological characteristics. Methods. 76 TNBC tissues were collected as the research object, while 60 adjacent tissues were used as controls. All patients underwent surgical treatment, and the expression of PD-L1 and BRCA1 in cancer tissues and adjacent tissues was detected by immunohistochemistry. At the same time, the relationship between PD-L1, BRCA1, and clinicopathological characteristics of patients with TNBC (including patient age, menopausal status, tumor size, lymph node metastasis, histological grade, Ki-67 expression, and p53 expression) were analyzed by univariate and logistic multivariate analysis. Results. The positive expression rate of PD-L1 in the TNBC group was 64.47%, which was higher than the control group by 41.67%. The positive expression rate of BRCA1 was 27.63%, which was lower than the control group by 48.33%. PD-L1 expression has no significant relationship with age, menopausal status, and p53 expression in TNBC patients. TNBC patients with tumors ≥2 cm, histological grade III, lymph node metastasis, and Ki-67 expression ≥20% had higher PD-L1 positive expression rates. The tumor size, Ki-67 expression, and PD-L1 expression of TNBC patients have independent effects. The expression of BRCA1 has no significant relationship with menopausal status, tumor size, Ki-67 expression, etc. TNBC patients with age

Some cancers such as human breast cancer, prostate cancer, and lung cancer easily metastasize to bone, leading to osteolysis and bone destruction accompanied by a complicated microenvironment. Systemic administration of bisphosphonates (BP) or denosumab is the routine therapy for osteolysis but with non-negligible side effects such as mandibular osteonecrosis and hypocalcemia. Thus, it is imperative to exploit optimized drug delivery systems, and some novel nanotechnology and nanomaterials have opened new horizons for scientists. Targeted and local drug delivery systems can optimize biodistribution depending on nanoparticles (NPs) or microspheres (MS) and implantable biomaterials with the controllable property. Drug delivery kinetics can be optimized by smart and sustained/local drug delivery systems for responsive delivery and sustained delivery. These delicately fabricated drug delivery systems with special matrix, structure, morphology, and modification can minimize unexpected toxicity caused by systemic delivery and achieve desired effects through integrating multiple drugs or multiple functions. This review summarized recent studies about optimized drug delivery systems for the treatment of cancer metastatic osteolysis, aimed at giving some inspiration in designing efficient multifunctional drug delivery systems.

PurposeN6-methyladenosine (m6A) is the most prevalent modification in mRNA methylation which has a wide effect on biological functions. This study aims to figure out the efficacy of m6A RNA methylation regulator-based biomarkers with prognostic significance in breast cancer.Patients and MethodsThe 23 RNA methylation regulators were firstly analyzed through ONCOMINE, then relative RNA-seq transcriptome and clinical data of 1,096 breast cancer samples and 112 normal tissue samples were acquired from The Cancer Gene Atlas (TCGA) database. The expressive distinction was also showed by the Gene Expression Omnibus (GEO) database. The gene expression data of m6A RNA regulators in human tissues were acquired from the Genotype-Tissue Expression (GTEx) database. The R v3.5.1 and other online tools such as STRING, bc-GeneExminer v4.5, Kaplan-Meier Plotter were applied for bioinformatics analysis.ResultsResults from ONCOMINE, TCGA, and GEO databases showed distinctive expression and clinical correlations of m6A RNA methylation regulators in breast cancer patients. The high expression of YTHDF3, ZC3H13, LRPPRC, and METTL16 indicated poor survival rate in patients with breast cancer, while high expression of RBM15B pointed to a better survival rate. Both univariate and multivariate Cox regression analyses revealed that age and risk scores were related to overall survival (OS). Univariate analysis also delineated that stage, tumor (T) status, lymph node (N) status, and metastasis (M) status were associated with OS. From another perspective, Kaplan-Meier Plotter platform showed that the relatively high expression of YTHDF3 and LRPPRC and the relatively low expression of RBM15B, ZC3H13, and METTL16 in breast cancer patients had worse Relapse-Free Survival (RFS). Breast Cancer Gene-Expression Miner v4.5 showed that LRPPRC level was negatively associated with ER and PR expression, while METTL16, RBM15B, ZC3H13 level was positively linked with ER and PR expression. In HER-2 (+) breast cancer patients, the expression of LRPPRC, METTL16, RBM15B, and ZC3H13 were all lower than the HER-2 (−) group.ConclusionThe significant difference in expression levels and prognostic value of m6A RNA methylation regulators were analyzed and validated in this study. This signature revealed the potential therapeutic value of m6A RNA methylation regulators in breast cancer.

Background The modified Clavien-Dindo classification system was employed to investigate the occurrence of early complications along with the related risk factors following a radical gastrectomy procedure, with the view of conducting an analysis into the impact of complications on long-term prognosis. Methods The clinical data of 525 patients who had previously undergone a radical gastrectomy procedure for gastric cancer were analyzed in a retrospective fashion. Results Postoperative hospital stay: Complication group (17.88±8.472) days, severe complications group (23.10±7.594) days, significantly higher than non-complication group (10.26±1.973) days and non-severe complications group (11.47±4.712) days (P=0.000 Conclusion Complications following radical gastrectomy were closely related to age, preoperative comorbidity, blood loss, and surgical approach; severe complications were closely related to blood loss, total gastrectomy, and nerve involvement; complications and severe complications were not found to be independent risk factors associated with long-term survival, that being said, they were significantly prolonged postoperative hospital stay.

Purpose N6-methyladenosine (m6A) is the most prevalent modification in mRNA methylation which has a wide effect on biological functions. This study aims to figure out the efficacy of m6A RNA methylation regulator-based biomarkers with prognostic significance in breast cancer. Patients and Methods The 23 RNA methylation regulators were firstly analyzed through ONCOMINE, then relative RNA-seq transcriptome and clinical data of 1,096 breast cancer samples and 112 normal tissue samples were acquired from The Cancer Gene Atlas (TCGA) database. The expressive distinction was also showed by the Gene Expression Omnibus (GEO) database. The gene expression data of m6A RNA regulators in human tissues were acquired from the Genotype-Tissue Expression (GTEx) database. The R v3.5.1 and other online tools such as STRING, bc-GeneExminer v4.5, Kaplan-Meier Plotter were applied for bioinformatics analysis. Results Results from ONCOMINE, TCGA, and GEO databases showed distinctive expression and clinical correlations of m6A RNA methylation regulators in breast cancer patients. The high expression of YTHDF3, ZC3H13, LRPPRC, and METTL16 indicated poor survival rate in patients with breast cancer, while high expression of RBM15B pointed to a better survival rate. Both univariate and multivariate Cox regression analyses revealed that age and risk scores were related to overall survival (OS). Univariate analysis also delineated that stage, tumor (T) status, lymph node (N) status, and metastasis (M) status were associated with OS. From another perspective, Kaplan-Meier Plotter platform showed that the relatively high expression of YTHDF3 and LRPPRC and the relatively low expression of RBM15B, ZC3H13, and METTL16 in breast cancer patients had worse Relapse-Free Survival (RFS). Breast Cancer Gene-Expression Miner v4.5 showed that LRPPRC level was negatively associated with ER and PR expression, while METTL16, RBM15B, ZC3H13 level was positively linked with ER and PR expression. In HER-2 (+) breast cancer patients, the expression of LRPPRC, METTL16, RBM15B, and ZC3H13 were all lower than the HER-2 (−) group. Conclusion The significant difference in expression levels and prognostic value of m6A RNA methylation regulators were analyzed and validated in this study. This signature revealed the potential therapeutic value of m6A RNA methylation regulators in breast cancer.

Purpose: The outbreak of novel coronavirus pneumonia occurred worldwide. 2019 novel coronavirus disease (COVID-19) can be transmitted from human to human, cause hospital infection, and seriously threatens surgical staffs and inpatients. The treatment of patients with breast cancer may be affected in this special period. Methods: From 24th January to 8th March 2020, patients diagnosed with breast cancer were enrolled from 16 hospitals in Jiangsu Province, and patients, who were candidates for surgery after neoadjuvant chemotherapy, were also enrolled. Patients from 24th January to 8th March 2019 were included as control with the same criteria. Results: In 2019, 520 patients were diagnosed with breast cancer in these 16 hospital; however, only 229 patients (decreased by 56%) were diagnosed with breast cancer in the same period of 2020. The clinical characteristics were similar between the two groups, and core biopsy was performed to more patients in 2020 than that in 2019 (4.1 days ±3.2 vs 3.2 days ±2.6, P < 0.001), and more patients underwent mastectomy and axillary lymph node dissection in 2020. After neoadjuvant chemotherapy, the mean interval between last time of neoadjuvant chemotherapy and surgery in 2020 was significantly longer than that in 2019 (29.2 days ±11.1 vs 17.7 days ±8.2, P < 0.001). After examinations to rule out COVID-19, no COVID-19 was found in any patient. Conclusions: In the special period of novel coronavirus pneumonia outbreak, the treatment of patients with breast cancer was delayed, but the treatment was safe after strict exclusions of COVID-19.

In the past decade, the study of exosomes, nanosized vesicles (50-150 nm) released into the extracellular space via the fusion of multivesicular bodies with the plasma membrane, has burgeoned with impressive achievements in theranostics applications. These nanosized vesicles have emerged as key players in homeostasis and in the pathogenesis of diseases owing to the variety of the cargos they can carry, the nature of the molecules packaged inside the vesicles, and the robust interactions between exosomes and target cells or tissues. Accordingly, the development of exosome-based liquid biopsy techniques for early disease detection and for monitoring disease progression marks a new era of precision medicine in the 21st century. Moreover, exosomes possess intrinsic properties - a nanosized structure and unique "homing effects" - that make them outstanding drug delivery vehicles. In addition, targeted exosome-based drug delivery systems can be further optimized using active targeting ligands such as nucleic acid aptamers. Indeed, the aptamers themselves can function as therapeutic and/or diagnostic tools based on their attributes of unique target-binding and non-immunogenicity. This review aims to provide readers with a current picture of the research on exosomes and aptamers and their applications in cancer theranostics, highlighting recent advances in their transition from the bench to the clinic.

Background The purpose of this study was to assess the effectiveness and safety in patients with benign phyllodes after performing local excision and following with intra-operative breast flap reconstruction. Methods Patients (n = 32) with eligible breast cystosarcoma phyllodes underwent wide local excision followed by intra-operative breast flap reconstruction. Primary outcome measures included average operative time, length of in-hospital stay, postoperative recurrence, and intra-operative and postoperative complications. Results Thirty-two patients who underwent surgical excision and oncoplastic breast surgery were evaluated using the BCCT.core software. A satisfactory symmetrical breast shape was achieved. The average operative time was 56.3 ± 8.2 min. The average postoperative duration of hospitalization was 3.7 ± 1.2 days. While there was no breast disease recurred during the 1 to 8-year follow-up period. Conclusions Wide local excision accompanied by intra-operative breast flap reconstruction could be adopted for removing benign phyllodes tumors while retaining the basic shape of the breast.

Both Th17 and Tc17 cells have been found in various tumors and may play important roles in regulating anti-tumor immune responses. However, the prevalence and distribution of Th17 and Tc17 cells in thyroid tumors are still unclear. In the current study, we examined the percentages of Th17 and Tc17 cells in the peripheral blood of 31 thyroid adenoma and 11 thyroid carcinoma patients. The serum IL-17 levels were also examined and their associations with Th17 and Tc17 cells were evaluated. Moreover, the presence of Th17 cells was detected in both thyroid adenoma and carcinoma patients. Our results showed that compared with healthy individuals, patients with thyroid tumors had a higher proportion of Th17 and lower proportion of Tc17 cells in peripheral blood. The serum concentration of IL-17 was significantly increased in patients with thyroid tumors and it was correlated with the percent of Th17 cells. Furthermore, the number of Th17 cells was significantly increased in the tumors of the patients. Th17 and Tc17 cells were negatively correlated with the tumor size. There was no significant difference between thyroid adenoma and carcinoma patients. These results indicate that Th17 cells may contribute to thyroid tumor pathogenesis.

Background We sought to investigate the clinical features of and risk factors for recurrent major depression (MD) with history of postpartum episodes (PPD) in Han Chinese women and the differences between first-onset postpartum MD (MD that has its first lifetime depressive episode in the postpartum period) and first-onset non-postpartum MD (MD with history of PPD and has its first lifetime depressive episode in a period other than postpartum). Methods Data were derived from the China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology (CONVERGE) study (N=6017 cases) and analyzed in two steps. We first examined the clinical features of and risk factors for MD patients with (N=981) or without (N=4410) a history of PPD. We then compared the differences between first-onset postpartum MD (N=583) and first-onset non-postpartum MD (N=398) in those with a history of PPD. Linear, logistic and multinomial logistic models were employed to measure the associations. Results A history of PPD was associated with more guilt feelings, greater psychiatric comorbidity, higher neuroticism, earlier onset and more chronicity (OR 0.2–2.8). Severe premenstrual symptoms (PMS) and more childbirths increased the risk of PPD, as did a family history of MD, childhood sexual abuse, stressful life events and lack of social support (OR 1.1–1.3). In the MD with history of PPD subsample, first-onset postpartum MD was associated with fewer recurrent major depressive episodes, less psychiatric comorbidity, lower neuroticism, less severe PMS and fewer disagreements with their husbands (OR 0.5–0.8), but more childbirths (OR 1.2). Limitations Data were obtained retrospectively through interview and recall bias may have affected the results. Conclusions MD with history of PPD in Han Chinese women is typically chronic and severe, with particular risk factors including severe PMS and more childbirths. First-onset postpartum MD and first-onset non-postpartum MD can be partly differentiated by their clinical features and risk factors, but are not clearly distinctive.

The value of gamma probes in the surgical treatment of secondary hyperparathyroidism (sHPT) was determined. The aim of this study was to enhance the rate of successful total parathyroidectomy in patients with sHPT using intraoperative gamma probe investigations.We retrospectively analyzed the clinical data of 48 sHPT patients between May 2007 and September 2011. Preoperative (99)Tc(m)- methoxyisobutyl isonitrile (MIBI) scintigraphy and high-frequency ultrasonography were used for parathyroid localization. Thirty-five patients (group I) underwent conventional neck exploration and open parathyroidectomy. Thirteen patients (group II) underwent gamma probe-guided total parathyroidectomy and parathyroid transplantation. The two groups were compared in terms of the number of parathyroid resections, operative time, and postoperative changes in the blood levels of parathyroid hormone (PTH), calcium, and phosphate.The clinical manifestations, PTH and calcium levels, age distribution, and clinical characteristics did not differ between the two groups. The accuracy of preoperative (99)Tc(m)-MIBI scintigraphy (89.74%) for the diagnosis of hyperparathyroidism did not differ from that of ultrasonography (81.25%). However, the accuracy of (99)Tc(m)-MIBI scintigraphy (66.67%) for localizing hyperfunctioning parathyroids was significantly lower than that of ultrasonography (76.86%). The operation time was significantly longer in group I ((120 ± 25) minutes) than in group II ((90 ± 30) minutes). The accuracy of parathyroid identification was significantly higher in group II (92.59%) than in group I (80.39%). On average, significantly fewer parathyroid specimens were obtained in group I (2.5 ± 0.5) than in group II (3.5 ± 0.5). Compared with group I, group II showed a significant increase (15.4%) in the number of parathyroid resections. The PTH, calcium, and phosphate levels significantly decreased postoperatively in all patients.Intraoperative gamma probe examination confirmed that the excised specimen was parathyroid tissue and improved the accuracy of parathyroid resection. The parathyroidectomy rate was increased by 15.4% due to the use of these probes. However, the probes did not detect all ectopic parathyroids, and further research is required to clarify the underlying reasons.

Background Bronchofiberscopy, a widely used procedure for the diagnosis of various pulmonary diseases within intensive care units, has a history of association with nosocomial infections. Between September and November 2009, an outbreak caused by multidrug-resistant Acinetobacter baumannii (MDR-Ab) was observed in the intensive care unit of a tertiary care hospital in Beijing, China. This study is aimed to describe the course and control of this outbreak and investigate the related risk factors. Methods Clinical and environmental sampling, genotyping with repetitive extragenic palindromic polymerase chain reaction (REP-PCR), and case–control risk factor analysis were performed in the current study. Results During the epidemic period, 12 patients were infected or colonized with MDR-Ab. Sixteen (72.7%) of twenty-two MDR-Ab isolates from the 12 patients and 22 (84.6%) of 26 MDR-Ab isolates from the bronchofiberscope and the healthcare-associated environment were clustered significantly into a major clone (outbreak MDR-Ab strain) by REP-PCR typing. Seven patients carrying the outbreak MDR-Ab strain were defined as the cases. Six of the seven cases (83%) received bronchofiberscopy versus four of the 19 controls (21%) (odds ratio, 22.5; 95% confidence interval, 2.07–244.84; P = 0.005). Several potential administrative and technical problems existed in bronchofiberscope reprocessing. Conclusions Bronchofiberscopy was associated with this MDR-Ab outbreak. Infection control precautions including appropriate bronchofiberscope reprocessing and environmental decontamination should be strengthened.

Here we report the draft genome sequence of one Acinetobacter genomic species 3 strain, D499, which harbors the bla NDM-1 gene. The total length of the assembled genome is 4,103,824 bp, and 3,896 coding sequences (CDSs) were predicted within the genome. A previously unreported bla NDM-1 -bearing plasmid was identified in this strain.

Published in Advance publications. This article has been retracted due to falsified data in Figures 1,4,5,S2 and S3 reporting tumor experiments on animals. The authors sincerely apologize to the scientific community for any confusion or adverse consequences resulting from the publication of this data.

e13512 Background: SLC35F2 is a member of solute carrier family 35 which encode nucleotide sugar transporters localizing in the Golgi apparatus and/or the endoplasmic reticulum, and transport nucle...

Background z-Guggulsterone (z-Gug) and Gugulipid (GL) have been used to treat a variety of ailments. We now report their anti-cancer effect and mechanism against human breast cancer. Methods Using the human estrogen receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cells as well as the normal human mammary epithelial cell line (HMEC), we evaluated the anti-breast-cancer efficacy and apoptosis inducing activity of GL. We determined the cellular and molecular mechanism of GL-inhibited breast cancer cell growth. Results GL significantly inhibited growth of MCF-7 and MDA-MB-231 cells with an IC50~2 μM at pharmacologically relevant concentrations standardized to its major active constituent z-Gug. The GL-induced growth inhibition correlated with apoptosis induction as evidenced by an increase in cytoplasmic histone-associated DNA fragmentation and caspase 3 activity. The GL-induced apoptosis was associated with down-regulation of the β-Catenin signaling pathway. The decreased expression of Wnt/β-Catenin targeting genes, such as cyclin D1, C-myc and survivin, and the inhibition of the activity of the transcription factor (T-cell factor 4, TCF-4) were observed in GL-treated breast cancer cells. The GL treatment resulted in a significant reduction of β-Catenin /TCF-4 complex in both of the cancer cells. The GL-induced apoptotic cell death was significantly enhanced by RNA Interference of β-Catenin and TCF-4. On the other hand, the normal human mammary epithelial cell HMEC, compared with the human breast cancer cells, is significantly more resistant to growth inhibition and apoptosis induction by GL. Conclusion The present study indicates that the β-Catenin signaling pathway is the target for GL-induced growth inhibition and apoptosis in human breast cancer.