Xiaowei Qi

Hypoxia induces RANK and RANKL expression by activating HIF-1α in breast cancer cells.

Receptor activator of NF-κB (RANK) and RANK ligand (RANKL) are known to play an important role in the development and progression of breast cancer. However, the mechanisms by which stimuli regulate the expression of RANK and RANKL in breast cancer cells are largely unknown. In this study, we show that hypoxia, a common feature of malignant tumors, can enhance the expression of RANK and RANKL mRNA and protein in MDA-MB-231 and MCF-7 breast cancer cells. In addition, we found that hypoxia induced hypoxia-inducible factor-1 alpha (HIF-1α) and phosphorylation of Akt, resulting in upregulation of RANK and RANKL expression; HIF-1α-targeted siRNA and PI3K-Akt inhibitor abrogated this upregulation in MDA-MB-231 cells. Furthermore, we also observed that hypoxia accelerated RANKL-mediated cell migration, which was inhibited following HIF-1α knockdown and PI3K-Akt inhibition. Thus, we provide evidence that hypoxia upregulates RANK and RANKL expression and increases RANKL-induced cell migration via the PI3K/Akt-HIF-1α pathway.

RANKL-induced migration of MDA-MB-231 human breast cancer cells via Src and MAPK activation

Accumulating studies have shown that the receptor activator of nuclear factor-κB ligand (RANKL)/RANK pathway plays an important role in tumor metastasis. However, the involvement of the RANKL/RANK signal transduction pathway in breast cancer metastasis remains unclear. The present study, therefore, investigated the role of downstream molecules of RANKL/RANK signaling in breast cancer cells using Transwell chemotaxis assays. RANKL was shown to direct the migration of MDA-MB-231 breast cancer cells. Osteoprotegerin (OPG; soluble decoy receptor of RANKL) inhibited RANKL-induced migration. RANKL activated Src kinase in MDA-MB-231 cells, as shown by Western blotting, and pretreatment with a Src inhibitor abrogated RANKL-induced cell migration, in a similar manner to OPG. Short-hairpin RNA against RANK, delivered via a lentiviral vector, significantly abolished the expression of phosphorylated Src. Stimulation by RANKL induced the phosphorylation of mitogen-activated protein kinases (MAPKs) (ERK, p38, JNK), and specific inhibitors of MAPKs blocked RANKL-induced cell migration. Furthermore, the expression of phosphorylated MAPKs could be blocked by a Src inhibitor and by small interfering RNA against Src. These findings suggest that Src and MAPK pathways may be involved in RANKL-induced MDA-MB-231 breast cancer cell migration.

Shrink pattern of breast cancer after neoadjuvant chemotherapy and its correlation with clinical pathological factors

BackgroundBreast conservation therapy (BCS) after neoadjuvant chemotherapy (NCT) can improve patients’ quality of life. Currently used intraoperative examination for negative margins may not be sufficient to detect microresidual foci, which are a risk factor for local recurrence. This study was conducted to investigate the shrinking pattern of breast cancer and residual tumors as a risk factor for BCS after NCT.MethodsNinety women with stage II or III invasive ductal carcinoma who achieved partial response after NCT with paclitaxel and epirubicin were enrolled. All patients had undergone modified radical mastectomy. One-half of the surgical specimens were subjected to subserial sectioning. Pathological changes of tumor bed and pericancerous tissues were examined with an optical microscope. The levels of estrogen receptors, progesterone receptors and HER2 were analyzed by immnohistochemical staining.ResultsThe residual tumors were classified into three types according to their microscopic morphology: solitary lesion, multifocal and patchlike lesions, and main residual tumor with satellite lesions. Type I residual tumors were found in 55 patients (61%), type II in 30 patients (33%) and type III in 5 patients (6%). Types II and III were often associated with larger primary tumors. The types of residual tumors were not correlated with the status of hormone receptors or HER2.ConclusionThree types of residual tumors were observed after NCT. The solitary residual tumor is most common, but main residual tumors with satellite lesions are most likely to cause local recurrence after BCS. Subserial sectioning would improve the identification of microfoci and patient survival after BCS.

Breast Cancer and Poland’s Syndrome: A Case Report and Literature Review

Abstract:  Poland’s syndrome is a rare congenital development malformation characterized by unilateral chest wall hypoplasia and ipsilateral hand abnormalities. It is also known to be associated with some malignant diseases. We herein report a case of Poland’s syndrome associated with invasive ductal carcinoma of breast, and review the literatures to investigate the clinical characteristics of breast cancer with Poland’s syndrome.

Association between the spread of circulating tumor cells and breast cancer subtypes.

We read with great interest the recent publication by Fehm and coworkers [1] about the association between the spread of circulating tumor cells (CTCs) and breast cancer subtypes. Th e authors observed that the highest CTC positivity rate was obtained in triple-negative patients followed by those with estrogen receptor (ER)positive and/or progesterone receptor (PR)-positive tumors, while no CTCs could be detected in the human epidermal growth factor receptor 2 (HER2)-positive subtype group. However, another study [2] showed contradictory results, indicating that HER2 was the only primary tumor characteristic that correlated with the presence of CTCs, while ER and PR status were not association with their presence. To clarify the correlation between CTCs and breast cancer subtypes, a total of 156 operable breast cancer patients admitted to our hospital were enrolled. Th is study was approved by the regional ethics committee. Written informed consent was obtained from all participating patients. Mononuclear cell enrichment and CTC detection were done as previously described [3]. Th e expression of ER, PR and HER2 in primary tumors was routinely detected. Results showed that the overall positive rate of CTCs in operable breast cancer patients was 32.1% (50 out of 156). Th ere existed signifi cant diff erences in the positive rate of CTCs between patients at diff erent pTNM stages (P = 0.0219) and between those with diff erent immunohisto chemical subtypes (P = 0.0003). Further analysis revealed that the positive rate of CTCs in the HER2positive and triple-negative subtypes was signifi cantly higher than that of the luminal subtype ( P= 0.0034 and 0.0003, respectively). In subgroup analysis by pTNM stage, signifi cant diff erences in the positive rate of CTCs between patients with diff erent breast cancer subtypes were identifi ed at stages I (P = 0.0207), II (P = 0.0478) and III (P = 0.0324) (Table 1), further supporting that the presence of CTCs was associated with the HER2-positive and triple-negative subtypes.

Implantation at sternocleidomastoid and chest wall after endoscopic thyroid carcinoma surgery.

Endoscopic thyroidectomy has been widely accepted by surgeons and patients for less postoperative pain, faster postoperative recovery, and excellent cosmetic effect. However, there still existed some limitations. Here, we reported a woman who suffered local implantation metastasis at sternocleidomastoid and chest wall after endoscopic thyroid carcinoma surgery. Although the implantation after endoscopic surgery is uncommon, this case reminds us to use endoscopic surgery for thyroid diseases with caution, especially for thyroid cancer. Following strict endoscopic surgery indications, comprehensive preoperative evaluation, meticulous intraoperative surgical handling, and effective protective measures, the incidence of locoregional implantation or recurrence might be dramatically reduced.

Endoscopic nipple sparing mastectomy with immediate implant-based reconstruction versus breast conserving surgery: a long-term study

To evaluate the differences between endoscopic nipple sparing mastectomy (ENSM) with immediate implant-based reconstruction and breast conserving surgery(BCS) applied to early-stage breast cancer in postoperative outcomes, function, and cosmesis. we made a prospective, non-randomized study reviewed a total of 346 cases of breast cancer from January 2007 to December 2011, including 189 cases of BCS and 157 cases of ENSM. All the patients were followed up to April 2016, with a median follow-up time of 74 months. The operative time, blood loss and drainage, postoperative complications, postoperative cosmesis, local recurrence rate, disease-free survival rate and overall survival rate of the two groups were compared. we found out that the operative time of ENSM was longer than that of BCS. There was no difference in blood loss and drainage, the postoperative complications, the disease-free survival rate and overall survival rate between the two groups. In regarding to cosmesis, patients in the ENSM group were more likely to get a satisfactory postoperative breast appearance. we reached a conclusion that ENSM is a safe and effective operative method retainingadvantages of TSSM to further improve the postoperative cosmetic effect, without increasing other risks. The surgery provides a new choice for patients with early-stage breast cancer.

Mammotome-assisted endoscopic breast-conserving surgery: a novel technique for early-stage breast cancer

BackgroundBecause of its minimally invasive and highly accurate nature, the use of Mammotome, a vacuum-assisted breast biopsy device has proven beneficial to the treatment of benign breast lesions. Taking advantage of endoscopic and Mammotome techniques together, we utilized the Mammotome device for therapeutic excision of malignant lesions in breast-conserving surgery (BCS).MethodsBetween December 2009 and January 2010, two patients with early breast cancer received Mammotome-assisted endoscopic BCSs. Under ultrasound monitoring, the Mammotome system dissected the surrounding tissue and freed the tumor en bloc leaving negative margins; endoscopic axillary lymph node dissection then followed.ResultsThe operation time was less than 180 minutes and the mean blood loss was 60 ml. The post-operative pathology report confirmed two patients to have invasive ductal carcinoma, one without axillary lymph nodes metastasis (0/11) and the other with one lymph node metastasis (1/21). No adverse events were noted. During a mean follow-up of 26.5 months, no evidence of recurrence or metastasis was found. The patients were satisfied with the cosmetic results.ConclusionsMammotome-assisted endoscopic surgery appears to be a valuable option for early breast cancer. The long-term therapeutic effect remains to be confirmed.

Role of Sphk1 in the malignant transformation of breast epithelial cells and breast cancer progression

BACKGROUND The ojective of the following study is to investigate the role of sphingosine kinase 1 (Sphk1) in the malignant transformation of breast epithelial cells and breast cancer progression and its mechanism. MATERIALS AND METHODS Immunohistochemistry was performed to detect Sphk1 and E-cadherin (E-cad) in resected breast samples. Sphk1 was transfected in normal human breast epithelial cell line (MCF-10A) by Lentivirus and silenced in breast cancer cell line (MCF-7) using small interfering ribonucleic acid. The effect of tumor necrosis factor alpha (TNF-α) and/or N, N-dimethylsphingosine (DMS) on the Sphk1 and E-cad expression, MCF-10A cell proliferation and invasion was investigated. Real time-polymerase chain reaction and western-blot was used to detect messenger ribonucleic acid and protein. Cell counting kit-8 and transwell were used to measure cell proliferation and invasion. RESULTS Sphk1 was positive expression in 114 breast tumors (75.50%) but negative in fibroadenomas. The expression of E-cad and Sphk1 were negatively correlated and E-cad (-)/Sphk1 (+) carriers showed higher ratio of axillary lymph node metastasis than E-cad (+)/Sphk1 (-) carriers. Overexpression of Sphk1 in MCF-10A reduced E-cad expression and improved cell proliferation and invasion, but knockdown of Sphk1 in MCF-7 decreased cell proliferation and invasion. TNF-α increased Sphk1 expression, enhanced the ability of Sphk1 in decreasing E-cad expression, which could be blocked by DMS. TNF-α promoted MCF-10A cell proliferation and invasion. CONCLUSION Sphk1 plays an important role in the malignant transformation of breast epithelial cells and modulates breast cancer metastasis through the regulation of E-cad expression. TNF-α can up-regulate Sphk1 expression and reduce E-cad expression through Sphk1, which can be blocked by DMS. TNF-α/Sphk1/E-cad pathway may be a newly discovered pathway and plays an important role in tumorigenesis and metastasis.

Adherence to Mediterranean diet and the risk of breast cancer: a meta-analysis

Background: For a long period of time, the Mediterranean diet (MD) has been regarded by many as a very healthy and balanced daily diet that may be related to the incidences of many types of cancer. However, the association between an MD and breast cancer risk remains inconsistent even though many studies about the topic have been conducted. Hence, we performed a meta-analysis to evaluate the relationship between an MD and breast cancer risk. Methods: We searched PubMed, Medline, and EMBASE for relevant articles published earlier than May 2017. “Mediterranean diet” combined with “breast cancer” and “breast carcinoma” were used as search terms. The combined relative risk (RR) and corresponding 95% confidence interval (CI) were used to evaluate the association between an MD and breast cancer risk. Results: A total of 18 articles were included in our meta-analysis; the studies spanned 11 years, ranging from 2006 to May 2017. Ten cohort and 8 case-control studies were included. Seven studies analyzed breast cancer incidence separately in premenopausal and postmenopausal women, whereas 6 studies were performed only in postmenopausal women, for a total of 13 analyses in postmenopausal women and 7 analyses among premenopausal women. Our meta-analysis revealed a significant and inverse association of the MD and breast cancer risk (RR: 0.92, 95% CI: 0.86, 0.99). Stratification analysis by study design and menopause status revealed a significant inverse association between the MD and breast cancer risk in case-control studies (RR: 0.85, 95% CI: 0.73, 0.99) and postmenopausal women (RR: 0.91, 95% CI: 0.85, 0.97) but not in cohort studies and premenopausal women. Conclusions: Our meta-analysis revealed that an MD is significantly associated with a reduction of breast cancer risk in women, especially postmenopausal women. The MD can be suggested to women, especially postmenopausal women, as a healthy diet to reduce breast cancer risk.