IKKα inhibition re-sensitizes acquired adriamycin-resistant triple negative breast cancer cells to chemotherapy-induced apoptosis.

IKKα has been shown to be responsible of multiple pro-tumorigenic functions and therapy resistance independent of canonical NF-κB, but its role in acquired chemotherapy resistance in breast cancer remains unclarified. In this study, we obtained pre-treatment biopsy and post-treatment mastectomy specimens from a retrospective cohort of triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy(NAC) (n = 43). Immunohistochemical methods were used to detect the expression of IKKα before and after NAC, and the relationship between IKKα and the pathologic response to NAC was examined. In addition, we developed a new ADR-resistant MDA-MB-231 cell line(MDA-MB-231/ADR) and analyzed these cells for changes in IKKα expression, the role and mechanisms of the increased IKKα in promoting drug resistance were determined in vitro and in vivo. We demonstrated that the expression of IKKα in residual TNBC tissues after chemotherapy was significantly higher than that before chemotherapy, and was positively correlated with lower pathological reaction. IKKα expression was significantly higher in ADR-resistant TNBC cells than in ADR-sensitive cells, IKKα knockdown results in apoptotic cell death of chemoresistant cells upon drug treatment. Moreover, IKKα knockdown promotes chemotherapeutic drug-induced tumor cell death in an transplanted tumor mouse model. Functionally, we demonstrated that IKKα knockdown significantly upregulated the expression of cleaved caspase 3 and Bax and inhibited the expression of Bcl-2 upon ADR treatment. Our findings highlighted that IKKα exerts an important and previously unknown role in promoting chemoresistance in TNBC, combining IKKα inhibition with chemotherapy may be an effective strategy to improve treatment outcome in chemoresistant TNBC patients.

Synergistic anticancer mechanisms of curcumol and paclitaxel in triple-negative breast cancer treatment may involve down-regulating ZBTB7A expression via the NF-B signaling pathway.

Objectives: This study aimed to verify whether curcumol combined with paclitaxel exerted synergistic antiproliferative and proapoptotic effects in MDA-MB-231 mammary cancer cells. Materials and Methods: The effects of different concentrations of CC, PTX, and their combination on the proliferation of MDA-MB-231 mammary cancer cells were determined by CCK-8 laboratory tests. Combination index (CI) was calculated using CompuSyn software. Colony formation assays, Hoechst 33258 immunofluorescence staining, and flow cytometry were carried out to observe proliferation and apoptosis in each group. The protein expression of PCNA, Bcl-2, Bax, ZBTB7A, p-p65, and NF-ƙB p65 was detected by western blotting. The xenograft tumor volume and body mass of nude mice were measured. Immunohistochemistry was used to detect the expression of PCNA , NF-B p65 and ZBTB7A. TUNEL and DAPI staining were used to detect the apoptosis of tumor cells. Results: Curcumol combined with paclitaxel exerted a significant inhibitory effect on proliferation of MDA-MB-231 cells in the CCK-8 laboratory test. Hoechst 33258 immunofluorescence staining, flow cytometry, TUNEL, and DAPI apoptosis staining demonstrated that cell apoptosis was the highest in the CC+PTX group in vivo and in vitro. Expression of PCNA, Bcl-2, ZBTB7A, p-p65, and NF-B p65 was lowest in the CC+PTX group, while the expression of Bax was highest. The growth of xenograft tumors in the CC+PTX group was most notably suppressed. Immunohistochemistry showed that expression of PCNA, ZBTB7A, and NF-ƙB p65 was the lowest in the CC+PTX group. Conclusion: Curcumol combined with paclitaxel exerted a synergistic antiproliferative and proapoptotic effect on triple-negative breast cancer cells.

Predictive and prognostic effect of HO-1 expression in breast cancer patients undergoing neoadjuvant chemotherapy.

PURPOSE: Heme oxygenase-1 (HO-1) has complex biological function, and is a candidate oncogene with a wide variety of deleterious functions in breast cancer. Here, we evaluated the relationship between expression of HO-1 protein with clinical response to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: We used immunohistochemistry (IHC) to determine expression of HO-1 protein from core needle biopsy before NAC, then applied univariate and multivariate analyses to understand the relationship between HO-1 with pathological complete response (pCR) outcomes. Next, Kaplan-Meier and Log-rank tests were used to compare disease-free survival (DFS) and overall survival (OS), between groups, and Cox proportional hazards regression analysis applied for prognostic evaluation. RESULTS: A total of 575 patients with locally advanced invasive breast cancer were included in the study, of which 111 (19.3%) achieved pCR after NAC. Results from multivariate analysis showed that high HO-1 expression was an independent predictor of low pCR rate (OR 0.254, 95% CI 0.026-0.643, p = 0.002). Moreover, results from survival analysis showed that high HO-1 expression was significantly associated with shorter DFS (HR 4.843, 95% CI 1.205-32.572, p = 0.026), but not with OS (HR 3.219, 95% CI 0.928-32.124, p = 0.071). Furthermore, HO-1 expression was significantly associated with lower pCR rate (OR 0.102, 95% CI 0.013-0.352), p = 0.001), poor DFS (HR 8.562, 95% CI 1.592-34.950, p = 0.009), and OS (HR 7.835, 95% CI 1.220-56.213, p = 0.023) of patients with triple-negative breast cancer (TNBC) patients. CONCLUSION: Our results indicated that HO-1 expression is not only a biomarker for predicting pCR, but also a prognostic factor in breast cancer patients in a neoadjuvant setting, especially in TNBC subgroups.

Significance of Oncotype DX 21-Gene Test and Expression of Long Non-Coding RNA MALAT1 in Early and Estrogen Receptor-Positive Breast Cancer Patients.

OBJECTIVE: To investigate the association between the recurrence score (RS) obtained by Oncotype DX 21-gene test and long non-coding RNA (lncRNA) MALAT1 expression in early and estrogen receptor-positive (ER+) breast cancer. MATERIALS AND METHODS: The Oncotype DX 21-gene test and MALAT1 expression detection were performed in tumor samples from 76 ER+ and early breast cancer patients with the Surplex liquid chip. The RS value was calculated based on the expression of total 21 genes. The level of MALAT1 was measured in both tumor tissue and para-tumor tissue, and relatively quantified with an internal control gene. Mann-Whitney U-test or Kruskal-Wallis test were used to analyze the association between MALAT1 level and different clinical pathological characteristics, including age, tumor stage, disease grade, lymph node status, Ki-67 expression, and progesterone receptor (PR) status. The association between the RS and different characteristics was analyzed by Wilcoxon rank-sum test. Correlation between two parameters was analyzed by Spearman's rank correlation analysis. RESULTS: The expression of MALAT1 was more abundant in tumor tissue (2.992 ± 2.256) than that in adjacent normal tissue (1.641±1.438, Z=-2.594, p=0.009), and it was not correlated with any clinical pathological characteristics. According to the old criteria for RS stratification, 52.7% of patients were in low risk (RS<18), 36.8% of patients were in medium risk (18≤RS≤30), and 10.5% of patients were in high risk (RS>30). While under the new criteria, 18.4% were in low risk group (RS<11), 63.2% were in a medium risk group (11≤RS≤26), and 18.4% were in a high risk group (RS>26). The Oncotype DX 21-gene results only correlated with Ki-67 expression under both new and old criteria, and it was not related with other cancer characteristics. The expression of lncRNA MALAT1 was significantly correlated with the Oncotype DX 21-gene results under the old criteria. CONCLUSION: MALAT1 is a novel breast cancer biomarker independent of tumor stage, disease grade and lymph node status. MALAT1 level is associated with the Oncotype DX 21-gene RS value. Therefore, combination of MALAT1 and the Oncotype DX 21-gene test may be used to predict prognosis in ER+ and early stage breast cancer.

Capsaicin Inhibits Proliferation and Induces Apoptosis in Breast Cancer by Down-Regulating FBI-1-Mediated NF-κB Pathway.

BACKGROUND: As a natural compound extracted from a variety of hot peppers, capsaicin has drawn increasing attention to its anti-cancer effects against multiple human cancers including breast cancer. FBI-1 is a major proto-oncogene negatively regulating the transcription of many tumor suppressor genes, and plays a vital role in tumorigenesis and progression. However, whether FBI-1 is involved in capsaicin-induced breast cancer suppression has yet to be ascertained. This study aimed to investigate the effects of capsaicin on proliferation and apoptosis and its association with FBI-1 expression in breast cancer. METHODS: CCK-8 and morphological observation assay were employed to detect cell proliferation. Flow cytometry and TUNEL assay were conducted to detect cell apoptosis. RNA interference technique was used to overexpress or silence FBI-1 expression. qRT-PCR and/or Western blot analysis were applied to detect the protein expression of FBI-1, Ki-67, Bcl-2, Bax, cleaved-Caspase 3, Survivin and NF-κB p65. Xenograft model in nude mice was established to assess the in vivo effects. RESULTS: Capsaicin significantly inhibited proliferation and induced apoptosis in breast cancer in vitro and in vivo, along with decreased FBI-1, Ki-67, Bcl-2 and Survivin protein expression, increased Bax protein expression and activated Caspase 3. Furthermore, FBI-1 overexpression obviously attenuated the capsaicin-induced anti-proliferation and pro-apoptosis effect, accompanied with the above-mentioned proteins reversed, whereas FBI-1 silencing generated exactly the opposite response. In addition, as a target gene of FBI-1, NF-κB was inactivated by p65 nuclear translocation suppressed with capsaicin treatment, which was perceptibly weakened with FBI-1 overexpression or enhanced with FBI-1 silencing. CONCLUSION: This study reveals that FBI-1 is closely involved in capsaicin-induced anti-proliferation and pro-apoptosis of breast cancer. The underlying mechanism may be related to down-regulation of FBI-1-mediated NF-κB pathway. Targeting FBI-1 with capsaicin may be a promising therapeutic strategy in patients with breast cancer.

Impact of Primary Site Surgery on Survival of Patients with de novo Stage IV Breast Cancer.

PURPOSE: The efficacy of primary site surgery in patients with de novo stage IV breast cancer remains controversial. However, few real-world studies have evaluated the benefits of local surgery on the primary site of stage IV breast cancer in China. The purpose of this study was to investigate the role of local surgery in the de novo stage IV breast cancer. MATERIALS AND METHODS: Women with metastatic breast cancer at diagnosis were identified from Guangxi medical university cancer hospital (China) database from 2009 to 2017. The clinical and tumor features, surgical treatment, and survival rates were compared between surgical and non-surgical patients. RESULTS: Two hundred forty-three patients were included, of whom 125 underwent primary site surgery. Patients who underwent surgery were more often had small primary tumors, fewer lymph node metastases, and had less visceral involvement. Patients in the surgery group had dramatically longer OS (median 35 vs 22 months, log-rank P=0.006). Stratified survival analysis showed that patients with bone metastasis alone or ≤3 metastasis benefit from surgery, while patients with visceral metastasis did not benefit from surgery. In multivariate analysis, surgical treatment, estrogen receptor status, progesterone receptor status and visceral metastases remained independent factors for survival. CONCLUSION: Surgical resection of the primary site can improve survival in selected de novo stage IV breast cancer patients.

Sodium Butyrate Combined with Docetaxel for the Treatment of Lung Adenocarcinoma A549 Cells by Targeting Gli1.

PURPOSE: This study is aimed to investigate the combined treating efficacy of sodium butyrate and docetaxel on proliferation and apoptosis of the lung adenocarcinoma A549 cell line based on Gli1 regulation in vitro and in vivo. MATERIALS AND METHODS: RNA interference method was used to overexpress Gli1 in A549 cells. Cells were treated with varying concentrations of sodium butyrate, docetaxel or both in combination. CCK-8, colony formation assay, Hoechst 33258 staining, flow cytometry and TUNEL assay were employed to detect proliferation, cell cycle and apoptosis. qRT-PCR and Western blot analysis were applied to detect the mRNA and protein expression of Gli1. In vivo tumorigenicity was detected by tumor transplantation in nude mice. Downstream protein levels of Gli1 were detected using Western blot assay. RESULTS: It was found that sodium butyrate or docetaxel alone, respectively, inhibited proliferation and promoted apoptosis of A549 cells in vitro and in vivo, while the combination of the two generated significantly higher responses, which were also effective in another lung adenocarcinoma cell line H1299. Furthermore, the combined therapy had an additive effect in suppressing Gli1 expression and regulating the expression of its downstream proteins that involve in proliferation, cell cycle and apoptosis of A549 cells in vitro and in vivo, including decreased protein expression of Ki-67, CDK1, CDK2, Cyclin D1, Bcl-2 and Survivin, and increased protein expression of Cyclin A, p21, Bax and cleaved-Caspase 3. On the other hand, Gli1 overexpression perceptibly reversed the above-mentioned additive effect in vitro and in vivo. CONCLUSION: This study demonstrates that the combined therapy of sodium butyrate and docetaxel additively inhibits proliferation and promotes apoptosis of A549 lung adenocarcinoma cells via suppressing Gli1 expression in vitro and in vivo. Targeting Gli1 by the combined therapy may provide new insights into the therapeutic management of patients with lung adenocarcinoma.

Prevalence of postmastectomy pain syndrome and associated risk factors: A large single-institution cohort study.

Postmastectomy pain syndrome (PMPS) is a frequent complication of breast surgery, and is considered a chronic neuropathic pain in the side of surgery which persists more than 3 months. We conducted a retrospective analysis of the largest reported cohort to investigate the prevalence of PMPS and to analyze its associated risk factors as well as the influence on quality of life (QoL). Two thousand thirty-three surgically-treated female patients diagnosed between 2012 and 2017 with early-stage breast cancer were asked to complete a questionnaire survey about their current chronic neuropathic pain problems and quality of life. Multivariate logistic regression analyses were applied to determine the associated risk factors of PMPS. Results have shown that 1983 (97.5%) patients responded and completed a questionnaire survey. Among them, PMPS was found in 28.2% of patients. In univariate analysis, age≤35 years, tumor staging, history of chronic pain, total mastectomy, and axillary lymph node dissection (ALND) were significantly correlated with PMPS (P < .05). Multivariate analysis showed that age≤35 years, history of chronic pain, total mastectomy, and ALND were the independent risk factors of PMPS. QoL outcomes have shown that the global QoL score, physical function score, role function score, and social function score in the PMPS group were reduced in the PMPS group (P < .05), while the difference in emotional function score and cognitive function score showed no statistical significance (P > .05). Besides, patients with PMPS have worse body image, sexual enjoyment, and more breast symptoms. In conclusion, PMPS is linked with a high incidence among breast cancer patients, and has a considerable negative influence on the quality of life. In addition, age, total mastectomy, ALND, and history of chronic pain are the independent risk factors of PMPS.

Long intergenic non-protein coding RNA 324 prevents breast cancer progression by modulating miR-10b-5p.

Mounting evidence suggests that long noncoding RNAs serve as specific biomarkers and potent modulators of multiple cancers. Long intergenic non-protein coding RNA 324 (LINC00324) is ubiquitously expressed in various tissues, including breast cancer. The biological function of LINC00324 in the development and progression of breast cancer remains unknown. Here, we fully elucidate the relation between LINC00324 expression and breast cancer, and suggest a potential mechanism of action. We found that decreased expression of LINC00324 was dramatically correlated with malignancy of breast cancer, both in breast cancer tissues and in cell lines. Overexpression of LINC00324 in MDA-MB-231 cells resulted in a decrease in cell proliferation, invasion, and migration, while increasing cells apoptosis. On the other hand, loss-of-function experiments indicated that deficiency of LINC00324 promoted malignant phenotypes in breast cancer cells. Mechanically, we found that LINC00324 is mainly distributed in the cytoplasm, fostering the expression of E-cadherin by sponging miR-10b-5p. Taken together, these findings suggest that LINC00324 plays a critical role in breast cancer progression by directly interacting with miR-10b-5p. LINC00324 can thus potentially act as an early diagnostic marker and a novel therapeutic agent for breast cancer.

ZBTB7A promotes migration, invasion and metastasis of human breast cancer cells through NF-κB-induced epithelial-mesenchymal transition in vitro and in vivo.

It has been generally confirmed that zinc finger and BTB domain containing 7A (ZBTB7A) plays an important role in the occurrence and progression of malignant tumours, but the promotion or inhibition effect is related to tumour type. The mechanism between ZBTB7A and breast cancer is not well understood, so further research is needed. In this study, we first investigated the expression of ZBTB7A in tissue samples of clinical breast cancer patients, MDA-MB-231, MCF-7 and MCF-10A cells. Second, we overexpressed the ZBTB7A in MCF-7 cells and silenced the ZBTB7A in MDA-MB-231 cells using lentivirus transfection technology, respectively, and verified the effect of ZBTB7A on migration and invasion of breast cancer cell lines through in vitro cell function experiments, such as wound-healing assay, migration and invasion assay, quantitative real time reverse transcriptase (qRT-PCR) and western blot. Then, the correlation between the above influences, epithelial-mesenchymal transition (EMT) and NF-κB was analysed. Finally, in vivo tumour transplantation model in nude mice was established to verified the effect of ZBTB7A on metastasis of breast cancer MDA-MB-231 cells. In conclusion, ZBTB7A is highly expressed in cancer tissue, breast cancer cell line MDA-MB-231 and MCF-7. Meanwhile, the high expression of ZBTB7A may promote cell migration, invasion and tumour metastasis, which may be related to EMT events by regulating NF-κB.

Triptolide Suppresses Growth of Breast Cancer by Targeting HMGB1 in Vitro and in Vivo.

Triptolide has been indicated potent anti-cancer effect involving multiple molecular targets and signaling pathways. High-mobility group box 1 (HMGB1) is a highly conserved DNA-binding protein taking part in breast cancer development. The therapeutic effect of triptolide on HMGB1 has not been reported. Thus, our study aims to clarify the role of HMGB1 in triptolide-induced anti-growth effect on breast cancer in vitro and in vivo. We demonstrated that triptolide significantly suppressed growth of breast cancer cells by inhibition of cell viability, clonogenic ability. Further studies evidenced that triptolide treatment not only inhibited HMGB1 mRNA expression, but also decreased supernatant level of HMGB1 in vitro. In line with these observations, exogenous recombinant HMGB1 (rHMGB1) promoted cell proliferation of breast cancer, and triptolide reversed the rHMGB1-promoted proliferative effect. As well, triptolide enhanced the anti-proliferative activity of ethyl pyruvate (EP) (HMGB1 inhibitor). Furthermore, downstream correlation factors (Toll-like receptor 4 (TLR4) and phosphorylated-nuclear factor-kappaB (NF-κB) p65) of HMGB1 were significantly decreased in vitro after triptolide treatment. Consistantly, we confirmed that tumor growth was significantly inhibited after triptolide treatment in vivo. Meanwhile, immunohistochemical analyses showed that triptolide treatment significantly decreased the level of cytoplasmic HMGB1 and TLR4 expression, whereas the expression of NF-κB p65 was relatively higher in cytoplasm, and conversely lower in nucleus as compared to the control group. Collectively, these results demonstrate that triptolide suppresses the growth of breast cancer cells via reduction of HMGB1 expression in vitro and in vivo, which may provide new insights into the treament of breast cancer.

A Novel Animal Model of Induced Breast Precancerous Lesion in Tree Shrew.

Chinese tree shrew, an animal exhibited closer evolutionary relationship with humans compared to rodents, is getting increasingly attentions as an appealing experimental animal model for human diseases. However, a high-efficiency and stable method to establish tree shrew breast precancerous lesions model has not been clearly elucidated. Thus, the current study aimed to explore the way of establishing breast precancerous model in tree shrew and investigate the pathologic characteristics of induced breast precancerous lesions. The results indicated that 7,12-dimethylbenz(a)anthracene (DMBA) could induce breast lesions in tree shrews. However, comparing to DMBA alone, an addition of medroxyprogesterone acetate (MPA) to DMBA critically increased the rate of induced breast lesion in tree shrews. Half of induced breast lesions were intraductal papilloma and the others were atypical ductal hyperplasia. Induced lesions showed positive expression of estrogen receptor α (ERα), progesterone receptor (PR) and cytokeratin 5/6 (CK5/6), but negative expression of human epidermal growth factor receptor-2 (Her-2). The expression of B cell lymphoma-extra large (Bcl-xl) was significantly higher and the expression of B cell lymphoma 2 associated X protein (Bax) was significantly lower in the precancerous lesions (atypical ductal hyperplasia) compared to benign tumor (intraductal papilloma). These results suggest that DMBA is able to induce breast lesions in tree shrews. Combination of DMBA and MPA may be more effective to establish breast precancerous lesion tree shrew models. Tree shrew might be a promising animal model for studying the tumorogenesis of breast cancer.

Efficacy of Iodine-125 Seed Implantation in Locoregionally Recurrent and Unresectable Breast Cancer: a Retrospective Study.

The management of locoregionally recurrent and unresectable breast cancer is a therapeutic challenge. This retrospective study aimed to assess the efficacy of 125I seed implantation brachytherapy as a palliative management in locoregionally recurrent breast cancer. We analyzed 36 locoregionally recurrent and unresectable breast cancers in our hospital between 2012 and 2016. All patients were treated with CT-guided 125I seed permanent implantation. The dose distribution of 125I seeds was calculated using a computerized treatment planning system. Complete response, partial response, stable disease, and local tumor control rates were calculated. Long-term efficacy was assessed based on survival rates ranging from 1 to 4 years. The follow-up period ranged from 6 to 53 months. The median local control was 28 months (95% CI: 16.2-39.8 months). The percentage of patients who showed 6-month, 1-year, 2-year, and 3-year local control was 97.2%, 77.8%, 52.8%, and 33.3%, respectively. Median survival time for all patients was 48 months (95% CI: 40.9-55.1 months); 1-year, 2-year, 3-year, and 4-year survival rates were 97.2%, 80.6%, 63.9%, and 46.5%, respectively. Pain relief response rate was 88.9%. No serious complications were detected during the follow-up period. The results of this study demonstrate that 125I seed implantation could be considered a feasible and promising minimally invasive therapy for locoregionally recurrent and unresectable breast carcinoma.

[Effects of FBI-1 silencing on proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231].

This work aimed to observe the effects of short hairpin RNA (shRNA)-silenced FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) on proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231. qRT-PCR and Western blot analysis were applied to detect the mRNA and/or protein expression of FBI-1, Bcl-2, Bax, cleaved-Caspase 3 and Survivin. RNA interference method was used to silence FBI-1 expression in MDA-MB-231 cells. CCK-8 and colony formation assay were employed to detect the cell proliferation. Flow cytometry was employed for examining cell apoptosis. In vivo tumorigenicity of MDA-MB-231 cells was detected by tumor transplantation in nude mice. The results showed that the mRNA and protein expressions of FBI-1 were higher in MDA-MB-231 cells compared with those in normal human mammary epithelial cells MCF-10A. FBI-1 gene silencing inhibited proliferation and induced apoptosis of MDA-MB-231 cells in vitro, together with decreased Bcl-2 and Survivin protein expression, increased Bax protein expression and activated Caspase 3. Moreover, FBI-1 gene silencing inhibited the tumorigenesis of MDA-MB-231 cells in vivo. These results suggest that silencing of FBI-1 gene inhibits proliferation, induces apoptosis and suppresses the tumorigenesis of MDA-MB-231 cells.

Elevated expression of POLD1 is associated with poor prognosis in breast cancer.

Polymerase δ catalytic subunit gene 1 (POLD1) may serve an important function in the development of tumors. However, its role in breast cancer remains unclear. The aim of the present study was to observe the expression and the function of POLD1 in breast cancer. A total of 84 patients with invasive breast carcinoma were recruited between 2011 and 2013. The expression of POLD1 was detected in paired tumor and adjacent normal tissues. Gene expression level of POLD1 was assessed using reverse transcription quantitative polymerase chain reaction. The protein expression of POLD1 was assessed using western blot analysis. The association between the clinicopathological features of patients with breast cancer and POLD1 expression was analyzed using a χ2 test. Disease-free survival (DFS) was analyzed using Kaplan-Meier method, and Cox regression analysis was performed to investigate clinicopathological significance of POLD1 expression. Additionally, the effects of POLD1 in regulating cell cycle and proliferation of MCF-7 cells were evaluated in vitro. The results demonstrated that gene and protein expression levels of POLD1 were significantly elevated in breast cancer tissues compared with those in adjacent normal tissues. Increased expression of POLD1 was significantly associated with positive lymph node status (P=0.028), histological grade (P=0.025), p53 status (P<0.001) and ki-67 index (P=0.020). Survival analysis demonstrated that increased expression of POLD1 was associated with poor DFS (P=0.033). Additionally, increased expression of POLD1 was associated with shorter DFS at early-stage (P=0.037), late-stage cases (P=0.023) and with the presence of triple-negative tumors (TNBC; P=0.049). Multivariate analysis revealed that POLD1 may be used as an independent prognostic factor in patients with breast cancer. In vitro studies revealed that downregulation of POLD1 suppressed cell cycle progression and proliferation in MCF-7 cells. In conclusion, POLD1 may be considered as a potential prognostic marker for invasive breast carcinoma.

SIRT1 promotes proliferation, migration, and invasion of breast cancer cell line MCF-7 by upregulating DNA polymerase delta1 (POLD1).

Sirtuin 1 (SIRT1), class III histone deacetylase, plays an important character in cell proliferation, cell cycle, apoptosis, energy metabolism and DNA repair. In recent years, researchers have attached increasing attention on the role of SIRT1 in tumorigenesis, development and drug resistance. The effect of SIRT1 on breast cancer is still controversial and its exact role remains to be elucidated. In the present study, we investigated the significant role of SIRT1 in breast cancer by exploring the effect of SIRT1 on DNA polymerase delta1 (POLD1), the gene coding for DNA polymerase δ catalytic subunit p125. Immunohistochemistry showed that the protein expression level of SIRT1 was higher in breast cancer tissues relative to adjacent normal tissues. Knockdown of SIRT1 by shRNA decreased the proliferation, migration, and invasion of human breast cancer cell line MCF-7, while the overexpression of SIRT1 promoted the proliferation, migration, and invasion of MCF-7 cells. Clinically, the immunohistochemistry results revealed that the expression of SIRT1 was positively correlated with p125. Further analysis demonstrated that silencing of SIRT1 increased the expression of p53, while the expression level of POLD1/p125 decreased, and the result by overexpressing SIRT1 was opposite. Collectively, these data suggest that SIRT1 is an oncogenic factor in breast cancer cells and can be involved in the progression of breast cancer by inhibiting p53 and activating POLD1. Our finding provides new insights into the mechanisms of breast cancer.

Oncological safety of nipple-sparing mastectomy in young patients with breast cancer compared with conventional mastectomy.

Although nipple-sparing mastectomy (NSM) is being used more frequently, the oncological safety of NSM remains unclear, particularly in young patients (<35 years). The aim of the present study was to compare the rates of local recurrence (LR), disease-free survival (DFS) and overall survival (OS) in young patients with breast cancer who had undergone NSM or conventional mastectomy (CM). The clinicopathological data of young patients with stage 0-IIB breast cancer who had undergone NSM (163 cases) or CM (194 cases) between 2007 and 2016 were retrospectively analyzed. The log-rank test was used to analyze the differences in the LR, DFS and OS rates between the two groups and multivariate analysis was used to analyze the patient prognostic factors for DFS. The median follow-up time was 49 months. Patients who had undergone CM were more likely to exhibit stage II disease (68.4 vs. 58.3%; P=0.015) and positive lymph nodes (45.9 vs. 33.1%; P=0.014). In the NSM group, LR occurred in 7 (4.3%) cases, systemic recurrence in 15 (9.2%) cases and mortality in 9 (5.5%) cases. In the CM group, LR occurred in 6 (3.1%) cases, systemic recurrence in 27 (13.9%) cases and mortality in 15 (7.7%) cases. There were no statistical differences in the LR, DFS and OS rates between the two groups (P>0.05). Following adjustment for clinical stage, the LR and DFS rates between the two groups exhibited no significant differences. Analysis of the prognostic factors demonstrated that clinical stage, lymph node status, estrogen and progesterone receptor status and human epidermal growth factor receptor 2 status were associated with DFS (P<0.05). NSM is safe for young patients with early-stage breast cancer and provides patients with an improved cosmetic outcome. Furthermore, nipple-areola complex preservation does not increase the risk of recurrence.

Postoperative outcomes of breast reconstruction after mastectomy: A retrospective study.

Breast reconstruction after mastectomy plays an active role in improving the quality-of-life (QoL) and alleviating the psychological trauma of breast cancer patients, and has become an indispensable part of the comprehensive treatment in breast cancer. However, compared with mastectomy alone, breast reconstruction also increase operative complications. The surgical, oncological outcomes, and cosmetic effect of breast reconstruction remains to be evaluated. Data for patients with breast cancer who underwent breast reconstruction after mastectomy from February 2009 to November 2015 in our hospital were retrospectively analyzed, with a median follow-up time of 44 months. The operating time, blood loss, drainage fluid, postoperative complications, postoperative cosmesis, oncological outcomes, and QoL were evaluated and compared between different reconstruction types. A total of 151 women were included. The flap-based group had higher complication rates of marginal necrosis of incision, while the incidence of capsular contracture was higher in immediate implant group. There was no difference in blood loss, drainage fluid, and other postoperative complications. Several independent factors were associated with increased postoperative complications included diabetic, obese, and reconstruction with flap. There was no significant difference in the disease-free survival rate and overall survival rate between different surgical groups. In terms of cosmetic effect, patients in the tissue expander group were more likely to get a satisfactory postoperative breast appearance. QoL outcomes shown that the tissue expander group has better body image and sexual enjoyment, while there was no significant difference for other QoL domains. In conclusion, different methods of breast reconstruction are safe and feasible for patients with breast cancer, tissue expander implantation following delayed implant breast reconstruction is a more effective treatment on cosmetic and QoL outcomes.