Lijun Ling

Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway.

Genistein (Gen) has been reported as a protective factor against breast cancer. However, the molecular mechanism by which Gen elicits its effects on triple-negative breast cancer cells has not been fully elucidated. In our study, the breast cancer cell line MDA-MB-231 was selected to determine the action of Gen on triple-negative breast cancer cells. MTT assay, flow cytometric analysis, siRNA transfection, western blotting and nuclear factor-κB (NF-κB) activation-nuclear translocation assay were used to address the role of NF-κB activity and the Notch-1 signaling pathway on the effects of Gen. Our study revealed that Gen elicited a dramatic effect on cell growth inhibition, in a dose-dependent and time-dependent manner. Treatment of MDA-MB-231 cells with 0, 5, 10 or 20 µM Gen induced apoptosis of 6.78, 18.98, 30.45 and 60.64%, respectively. Exposure of MDA-MB-231 cells to Gen also resulted in G2/M phase accumulation of cells corresponding to 4.93, 12.54, 18.93 and 30.95%, respectively. Furthermore, our data demonstrated for the first time that Gen inhibited the growth of MDA-MB-231 triple-negative breast cancer cells by inhibiting NF-κB activity via the Nocth-1 signaling pathway in a dose-dependent manner. We also found that Gen downregulated the expression of cyclin B1, Bcl-2 and Bcl-xL, possibly mediated by NF-κB activation via the Notch-1 signaling pathway. In conclusion, our results suggest that inhibition of NF-κB activity via the Notch-1 pathway may be a novel mechanism by which Gen suppresses the growth of triple-negative breast cancer cells. Further preclinical and clinical studies are warranted to further investigate the application of Gen for the treatment of triple-negative breast cancer.

Intraoperative ultrasound guidance is associated with clear lumpectomy margins for breast cancer: a systematic review and meta-analysis.

Purpose Margin status is one of the most important predictors of local recurrence after breast conserving surgery (BCS). Intraoperative ultrasound guidance (IOUS) has the potential to improve surgical accuracy for breast cancer. The purpose of the present meta-analysis was to determine the efficacy of IOUS in breast cancer surgery and to compare the margin status to that of the more traditional Guide wire localization (GWL) or palpation-guidance. Methods We searched the database of PubMed for prospective and retrospective studies about the impact of IOUS on margin status of breast cancer, and a meta-analysis was conducted. Results Of the 13 studies included, 8 were eligible for the impact of IOUS on margin status of non-palpable breast cancers, 4 were eligible for palpable breast cancers, and 1 was for both non-palpable and palpable breast cancers. The rate of negative margins of breast cancers in IOUS group was significantly higher than that in control group without IOUS (risk ratio (RR)  = 1.37, 95% confidence interval (CI)  = 1.18–1.59 from 7 prospective studies, odds ratio (OR)  = 2.75, 95% CI  = 1.66–4.55 from 4 retrospective studies). For non-palpable breast cancers, IOUS-guidance enabled a significantly higher rate of negative margins than that of GWL-guidance (RR  = 1.26, 95% CI  = 1.09–1.46 from 6 prospective studies; OR  = 1.45, 95% CI  = 0.86–2.43 from 2 retrospective studies). For palpable breast cancers, relative to control group without IOUS, the RR for IOUS associated negative margins was 2.36 (95% CI  = 1.26–4.43) from 2 prospective studies, the OR was 2.71 (95% CI  = 1.25–5.87) from 2 retrospective studies. Conclusion This study strongly suggests that IOUS is an accurate method for localization of non-palpable and palpable breast cancers. It is an efficient method of obtaining high proportion of negative margins and optimum resection volumes in patients undergoing BCS.

Molecular subtype classification is a determinant of non-sentinel lymph node metastasis in breast cancer patients with positive sentinel lymph nodes.

Background Previous studies suggested that the molecular subtypes were strongly associated with sentinel lymph node (SLN) status. The purpose of this study was to determine whether molecular subtype classification was associated with non-sentinel lymph nodes (NSLN) metastasis in patients with a positive SLN. Methodology and Principal Findings Between January 2001 and March 2011, a total of 130 patients with a positive SLN were recruited. All these patients underwent a complete axillary lymph node dissection. The univariate and multivariate analyses of NSLN metastasis were performed. In univariate and multivariate analyses, large tumor size, macrometastasis and high tumor grade were all significant risk factors of NSLN metastasis in patients with a positive SLN. In univariate analysis, luminal B subgroup showed higher rate of NSLN metastasis than other subgroup (P = 0.027). When other variables were adjusted in multivariate analysis, the molecular subtype classification was a determinant of NSLN metastasis. Relative to triple negative subgroup, both luminal A (P = 0.047) and luminal B (P = 0.010) subgroups showed a higher risk of NSLN metastasis. Otherwise, HER2 over-expression subgroup did not have a higher risk than triple negative subgroup (P = 0.183). The area under the curve (AUC) value was 0.8095 for the Cambridge model. When molecular subtype classification was added to the Cambridge model, the AUC value was 0.8475. Conclusions Except for other factors, molecular subtype classification was a determinant of NSLN metastasis in patients with a positive SLN. The predictive accuracy of mathematical models including molecular subtype should be determined in the future.

Incidence of chemotherapy-induced amenorrhea associated with epirubicin, docetaxel and navelbine in younger breast cancer patients

BackgroundThe rates of chemotherapy-induced amenorrhea (CIA) associated with docetaxel-based regimens reported by previous studies are discordant. For navelbine-based chemotherapies, rates of CIA have seldom been reported.MethodsOf 170 premenopausal patients recruited between January 2003 and September 2008, 78 were treated with fluorouracil plus epirubicin and cyclophosphamide (FEC), 66 were treated with docetaxel plus epirubicin (TE), and 26 were treated with navelbine plus epirubicin (NE). Patient follow-up was carried up every 3-4 months during the first year, then every 9-12 months during subsequent years.ResultsIn univariate analysis, the rates of CIA were 44.87% for the FEC regimen, 30.30% for the TE regimen and 23.08% for the NE regimen (P = 0.068). Significant differences in the rates of CIA were not found between the FEC and TE treatment groups (P > 0.05), but were found between the FEC and NE treatment groups (P < 0.05). Furthermore, no significant differences were found between the TE and NE regimens (P > 0.05). Tamoxifen use was a significant predictor for CIA (P = 0.001), and age was also a significant predictor (P < 0.001). In multivariate analysis, age (P < 0.001), the type of chemotherapy regimens (P = 0.009) and tamoxifen use (P = 0.003) were all significant predictors.ConclusionsAge and administration of tamoxifen were found to be significant predictive factors of CIA, whereas docetaxel and navelbine based regimens were not associated with higher rates of CIA than epirubicin-based regimen.

Reproductive factors and breast cancer risk among BRCA1 or BRCA2 mutation carriers: Results from ten studies

Although reproductive factors are among the most well-established risk factors for breast cancer in the general population, it is still a matter for debate whether these factors act as risk modifiers among BRCA1 or BRCA2 mutation carriers. This meta-analysis is the first to be performed to determine the relationship between reproductive factors and breast cancer risk among BRCA1 and BRCA2 mutation carriers. We searched the PubMed database up to February 2013. A total of ten studies met the inclusion criteria. The results showed that the reproductive factors may be associated with breast cancer risk only among BRCA1 mutation carriers. No association was found between parity and breast cancer risk. Compared with women at the youngest age in the first-birth category, women in the oldest age category were at a 38% lower risk of breast cancer (RR=0.62, 95%CI=0.45-0.85). Breastfeeding for at least 1 or 2 years was associated with a 37% reduction in breast cancer risk (RR=0.63, 95%CI=0.46-0.86). Women at the oldest age in the menarche category were at a 34% lower risk of breast cancer (RR=0.66, 95%CI=0.53-0.81) than women in the youngest age category. However, none of the reproductive factors were associated with breast cancer risk among BRCA2 mutation carriers. In conclusion, late age at first birth, breastfeeding, and late age at menarche protect against breast cancer in BRCA1 mutation carriers only. Further studies are needed to explore the mechanisms.

Comparison of Ablation Zones among Different Tissues Using 2450-MHz Cooled-Shaft Microwave Antenna: Results in Ex Vivo Porcine Models

Background For complete tumor ablation in different tissues, it is necessary to investigate the exact coagulation zone of microwave ablation in different tissues. The aim of this study was to compare the extent of microwave ablation zone in muscle, liver and adipose tissue in ex vivo porcine models and assess the shape of microwave coagulation zone among these tissues. Materials and Methods Microwave ablations were performed in ex vivo porcine muscle, liver and adipose tissue using 2450-MHz cooled-shaft microwave antenna. The content of water, fat and protein in these three tissues was determined. Two power increments (40 and 80 W) and five time increments (1, 3, 5, 7, and 10 minutes) were used in this study. Diameters and shapes of the ablation zones were assessed on gross specimens. Results The average percentages of water, fat and protein in these three tissues were significantly different (P < 0.001), respectively. The long-axis and short-axis diameters among these three tissues at each time-power combination were not significantly different (P > 0.05). The coagulation zones were all elliptical in muscle, liver and adipose tissue. When microwave ablation was performed in the tissue containing both muscle and adipose tissue, the coagulation zone was also elliptical. Regardless of the output power, the ellipticity index (EI) value of 1 minute treatment duration was higher than that of 10 minutes treatment duration (P < 0.05). Furthermore, the EI value did not decrease significantly when the treatment duration was more than 5 minutes (P > 0.05). Conclusion The extent of microwave ablation zones was not significantly different among completely different tissues. Microwave ablations with ≥ 5 minutes time duration can induce coagulation zones with clinical desirable shape. Future clinical studies are still required to determine the role of microwave ablation in different tissues.

Image and pathological changes after microwave ablation of breast cancer: a pilot study.

PURPOSE To prospectively assess MR imaging evaluation of the ablation zone and pathological changes after microwave ablation (MWA) in breast cancer. MATERIALS AND METHODS Twelve enrolled patients, diagnosed with non-operable locally advanced breast cancer (LABC), were treated by MWA and then neoadjuvant chemotherapy, followed by surgery. MR imaging was applied to evaluate the effect of MWA. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were applied to analyze the ablated area. RESULTS All MWA procedures were performed successfully under local anesthesia. For a mean duration of 2.15 min, the mean largest, middle and smallest diameters in the ablated zone 24-h post-ablation in MR imaging were 2.98 cm ± 0.53, 2.51 cm ± 0.41 and 2.23 cm ± 0.41, respectively. The general shape of the ablation zone was close to a sphere. The ablated area became gradually smaller in MR imaging. No adverse effects related to MWA were noted in all 12 patients during and after MWA. HE staining could confirm the effect about 3 months after MWA, which was confirmed by TEM. CONCLUSIONS 2 min MWA can cause an ablation zone with three diameters larger than 2 cm in breast cancer, which may be suitable for the local treatment of breast cancer up to 2 cm in largest diameter. However, the long-term effect of MWA in the treatment of small breast cancer should be determined in the future.

A novel mouse model of gastric cancer with human gastric microenvironment.

Mouse models play an irreplaceable role in the in vivo research of human gastric cancer. In this study, we developed a novel human Gastric tissue-derived Orthotopic and Metastatic (GOM) mouse model of human gastric cancer, in which the human normal gastric tissues were implanted subcutaneously into immunodeficient mice to create a human gastric microenvironment. Then, human gastric cancer cells were injected into the implants. GOM model could mimic the interactions between human gastric microenvironment and human gastric cancer cells, which help exhibit the real characteristics of tumor cells, and finally mimic the clinical-like tumor proliferation and metastases of human beings.

Low serum creatine kinase levels in breast cancer patients: a case-control study.

Background Previous studies provide an ambiguous picture of creatine kinase (CK) expression and activities in malignancy. The aim of this study was to investigate the role of serum CK level in breast cancer patients. Patients and Methods 823 female patients diagnosed with breast cancer were consecutively recruited as cases, and 823 age-match patients with benign breast disease were selected as controls. Serum CK was analyzed by commercially available standardized methods. Results Serum CK level was significantly associated with breast cancer (P = 0.005) and subtypes of breast cancer, including breast cancer with diameter>2 cm (P = 0.031) and stage IIIbreast cancer (P = 0.025). The mean serum CK level in patients with>2 cm tumor was significantly lower than that in≤2 cm (P = 0.0475), and the mean serum CK level of stage III breast cancer patients was significantly lower than that of stage I and II breast cancer patients (P = 0.0246). Furthermore, a significant difference (P = 0.004) was observed between serum CK level and ERBB2+breast cancer not other molecular subtypes. Conclusions Serum CK levels in cases was significantly lower compared with controls. Notably, our results indicated for the first time that there was a negative correlation between serum CK levels and breast cancer stage. Serum CK level, which may reflect the status of host immunity, may be an important factor in determining breast cancer development and progression.

Family history and risk of ductal carcinoma in situ and triple negative breast cancer in a Han Chinese population: a case–control study

BackgroundThe association between family history and risk of triple negative breast cancer and ductal carcinoma in situ (DCIS) has not been well investigated, especially in Asian populations. We investigated the association between family history and risk of DCIS or triple negative breast cancer in a Han Chinese population.MethodsA case–control study, comprising 926 breast cancer patients and 1,187 benign breast disease controls, was conducted in our hospital. Multivariate logistic regression was used to assess the relationships between family history and risk of DCIS or triple negative breast cancer.ResultsSubjects with a family history of breast cancer had higher breast cancer risk than those without a family history (odds ratio (OR) = 2.11, 95% confidence interval (CI) = 1.26 to 3.52). Family history was not significantly associated with an increased risk of DCIS (OR = 1.27, 95% CI = 0.36 to 4.46), while family history was significantly associated with an increased risk of invasive breast cancer (OR = 2.22, 95% CI = 1.32 to 3.75), irrespective of triple negative breast cancer (OR = 3.35, 95% CI = 1.43 to 7.88) or non-triple negative breast cancer (OR = 2.14, 95% CI = 1.21 to 3.80).ConclusionOur results indicate that having a family history of breast cancer is associated with an increased risk of triple negative breast cancer with a magnitude of association similar to that for non-triple negative breast cancer. Furthermore, family history is not significantly associated with an increased risk of DCIS. Future cohort studies with larger sample sizes are still needed to explore these relationships.