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ABSTRACT: The extracts prepared from Liriodendron tulipifera Linn., L. chinense (Hemsl.) Sarg., and their hybrid L. chinense x L. tulipifera, were investigated for their cytotoxic abilities in vitro against five human cancer cell lines: MDA-MB-231 and MCF-7 breast cancer cells, SGC-7901 gastric cancer cells, HuH-7 hepatocarcinoma cells, and HCT-15 colon carcinoma cells, and then measured their phenols and alkaloids contents. Of these plant extracts, some of them, especially the lower polar extracts from barks, exhibited potent cytotoxic effects on five tested tumor cell lines.
Pakistan journal of pharmaceutical sciences 03/2013; 26(2):233-7. · 1.10 Impact Factor
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Ming-Jie Zheng,
Jue Wang,
Yuan-Wen Chen,
Lu Xu,
Dan-Dan Xue,
Wei Fu,
Yi-Fen Zhang,
Qing Du,
Yi Zhao,
Li-Jun Ling, Qiang Ding,
Xiao-An Liu,
Xiao-Ming Zha,
Wei Zheng,
Tian-Song Xia,
Shui Wang
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ABSTRACT: 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.
Cancer letters 06/2012; 325(1):108-15. · 4.86 Impact Factor
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ABSTRACT: Background: The relationship between postmenopausal hormone therapy (HT) and invasive breast cancer has been extensively investigated, but that with breast carcinoma in situ (BCIS) has received relatively little attention. The aim of our present study was to review and summarize the evidence provided by longitudinal studies on the association between postmenopausal HT use and BCIS risk. Methods: A comprehensive literature search for articles published up to May 2012 was performed. Prior to performing a meta-analysis, the studies were evaluated for publication bias and heterogeneity. Relative risk (RR) or odds ratio (OR) values were calculated using 14 reports (8 case-control studies and 6 cohort studies), published between 1986 and 2012. Results: There was evidence of an association between ever postmenopausal estrogen use and BCIS based on a random-effects model (RR = 1.25, 95% confidence interval (CI) = 1.01, 1.55). However, we found no strong evidence of an association between ever postmenopausal estrogen combined with progesterone use and BCIS using a random- effects model (RR = 1.55, 95% CI = 0.95, 2.51). Furthermore, our analysis showed a strong association between " > 5 years duration" of estrogen or estrogen combined with progesterone use and BCIS. Furthermore, current use of any HT is associated with increased risk of BCIS in cohort studies. Additional well-designed large studies are now required to validate this association in different populations.
Asian Pacific journal of cancer prevention: APJCP 01/2012; 13(8):3917-25. · 0.66 Impact Factor
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ABSTRACT: Nipple discharge is a common complaint of patients with breast disease. The color of nipple discharge is always the first alarming symptom for patients. It is controversial whether the discharge color is an indicator of an underlying malignancy. The electronic database PubMed was searched for relevant articles. A meta-analysis about the association between the color of nipple discharge and breast cancer risk was conducted. Eight studies, including 3,110 patients, were eligible for this meta-analysis. Compared with patients in non-bloody nipple discharge group (179/1,478), patients in bloody nipple discharge group (404/1,632) had a markedly higher breast cancer risk (OR: 2.27, 95% CI: 1.32-3.89, P < 0.001 for heterogeneity). Compared with patients in clear/serous group (71/575), patients in bloody nipple discharge group (326/1,271) also had a higher risk (OR: 2.49, 95% CI: 1.25-4.93, P = 0.011 for heterogeneity). Furthermore, compared with patients in the colored group (55/448), patients in bloody nipple discharge group (296/1,124) (OR: 2.00, 95% CI: 0.74-5.45, P = 0.009 for heterogeneity) had no significant difference. Besides, there was no significant difference between patients in colored group (55/448) and clear/serous group (61/470) (OR: 1.35, 95% CI: 0.83-2.18, P = 0.707 for heterogeneity). Therefore, bloody nipple discharge could be a predictor of breast cancer risk among different colors of discharges. The symptom of bloody nipple discharge is helpful to the stratification of preoperative patients.
Breast Cancer Research and Treatment 09/2011; 132(1):9-14. · 4.43 Impact Factor
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ABSTRACT: Benign breast disease (BBD) is an important risk factor for subsequent breast cancer. However, it is unclear whether breast cancer risk is higher in cases of atypical ductal hyperplasia (ADH) than atypical lobular hyperplasia (ALH). Furthermore, it is unclear whether family history increases risk in women with various subtypes of BBD.
We searched the electronic database of PubMed for case-control studies about the subsequent breast cancer risk of BBD, and a meta-analysis was conducted.
Of ten inclusive studies, nine were eligible for subsequent breast cancer risk of histological subtype, including 2,340 cases and 4,422 controls, and four were eligible for investigating the influence of family history on subtypes of BBD, including 1,377 cases and 2,630 controls. Relative to non-proliferative disease (NP), all subtypes of BBD increased subsequent risk, and risk for women with ALH (OR = 5.14, 95% CI 3.52-7.52) may be higher than for women with ADH (OR = 2.93, 95% CI 2.16-3.97). Compared to women without family history and proliferative disease, women with a first-degree family history and atypical hyperplasia (AH) were at highest risk (OR = 4.87, 95% CI 2.89-8.20). Relative to women without family history, women with a first-degree family history had an increased breast cancer risk in different histological subtypes of BBD except for AH (OR = 1.39, 95% CI 0.82-2.37).
This meta-analysis strongly suggested that women with AH, especially for ALH and AH combined with a first-degree family history, were at high risk, for whom risk-reduction options should be considered.
Journal of Cancer Research and Clinical Oncology 07/2011; 137(7):1053-60. · 2.56 Impact Factor
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Tian-Song Xia,
Guo-Zhu Wang, Qiang Ding,
Xiao-An Liu,
Wen-Bin Zhou,
Yi-Fen Zhang,
Xiao-Ming Zha,
Qing Du,
Xiao-Jian Ni,
Jue Wang,
Su-Yu Miao,
Shui Wang
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ABSTRACT: In practice, investigations for bone metastasis of breast cancer rely heavily on models in vivo. Lacking of such ideal model makes it difficult to study the whole process or accurate mechanism of each step of this metastatic disease. Development of xenograft mouse models has made great contributions in this area. Currently, the best animal model of breast cancer metastasizing to bone is NOD/SCID-hu models containing human bone, which makes it possible to let the breast cancer cells and the bone target of osteotropic metastasis be both of human origin. We have developed a novel mouse model containing both human bone and breast, and proved it functional and reliable. In this study, a set of human breast cancer cell line including MDA-MB-231, MDA-MB-231BO, MCF-7, ZR-75-1 and SUM1315 were characterized their osteotropism in this model. A specific cell line SUM1315 made species-specific bone metastasis, certifying the osteotropism-identification utility of the novel mouse model. Furthermore, gene expression and microRNA expression profiling analysis were done to the two SUM1315 derived sub lines isolated and purified from the orthotopic and metastatic xenograft. In addition, to demonstrate the disparity between the "spontaneous" and "forced" bone metastasis in mouse model, MDA-MB-231 cells were inoculated into both the human implants in this model simultaneously, and then primary cultured and profiling analyzed. Supported by overall results of profiling analyses, this study suggested the novel model was a useful tool for understanding, preventing and treating bone metastasis of breast cancer, meanwhile it had provided significant information for further investigations.
Breast Cancer Research and Treatment 06/2011; 132(2):471-86. · 4.43 Impact Factor
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ABSTRACT: Compared to tamoxifen, the efficacy and side effects of toremifene in adjuvant endocrine therapy for breast cancer were not very clear. This meta-analysis was conducted to give a more precise estimation of the efficacy and severe side effects of toremifene given in the adjuvant setting in comparison to tamoxifen. The electronic database PubMed was searched for randomized trials comparing toremifene with tamoxifen as adjuvant therapies. Four randomized trials published in three articles were eligible, including 1,890 pooled cases treated with toremifene and 1,857 cases treated with tamoxifen. Compared to patients in tamoxifen group, patients in toremifene group did not have a significantly different overall survival rate (risk ratio (RR): 1.07, 95% confidence interval (CI): 0.97-1.19, P = 0.994 for heterogeneity) or a disease-free survival (DFS) rate (RR: 1.05, 95% CI: 0.95-1.17, P = 0.431 for heterogeneity) at the end of the follow-up time. The rates of thromboembolic events in toremifene group, including deep vein thrombosis (odds ratio (OR): 0.68, 95% CI: 0.40-1.17, P = 0.926 for heterogeneity), cerebrovascular accident (OR: 0.59, 95% CI: 0.32-1.09, P = 0.438 for heterogeneity), and pulmonary embolism (OR: 0.91, 95% CI: 0.42-2.01, P = 0.618 for heterogeneity), were not significantly different from those in tamoxifen group. The rates of endometrial polyps and endometrial cancer between the two groups were almost the same. This meta-analysis suggested that toremifene was as effective as tamoxifen in the adjuvant setting for both perimenopausal and postmenopausal breast cancer patients with similar severe adverse effects to tamoxifen. Toremifene was a convincing and safe change for tamoxifen in adjuvant endocrine therapy.
Breast Cancer Research and Treatment 05/2011; 128(3):625-31. · 4.43 Impact Factor
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ABSTRACT: Spleen tyrosine kinase (Syk) is reported to be involved in the suppression of proliferation and invasion of breast cancer. Methylation-mediated Syk gene silencing is found in a subset of breast cancer. In this study, we used a DNA methyltransferase inhibitor, 5-aza-2-deoxycytidine (AZA), to restore Syk expression of breast cancer cells. Surprisingly, we found that AZA treatment could reestablish the expression of Syk, but not affect the proliferation of breast cancer cells. Moreover, tumor formation in situ by MDA-MB-435s treated with (+) or without (-) AZA in a nude mice MFP (Mammary fat pad) model did not show significant difference, too. Interestingly, pulmonary metastasis was still significantly suppressed in MDA-MB-435s(+) group (1/9 vs. 7/9). Our findings suggested Syk may be more correlated to metastasis rather than proliferation. This study implied a potential use of Syk methylation as a valuable biomarker to detect high metastatic potential cancerous lesions and the prospect of AZA to join the arsenal of drug candidates to be developed as a new reagent for management of advanced breast cancer.
Medical Oncology 02/2011; 29(2):448-53. · 2.14 Impact Factor
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ABSTRACT: Synuclein gamma (SNCG), previously identified as a breast cancer-specific gene, is highly expressed in malignant cancer cells but not in normal epithelium. The molecular targets of SNCG during breast cancer progression have not been fully identified. Here we analyzed the effect of SNCG on stimulation of membrane-initiated estrogen signaling. While SNCG expression enhanced estrogen-induced activation of ERK1/2 and mammalian target of rapamycin, knockdown of endogenous SNCG decreased membrane-initiated estrogen signaling. SNCG functions as a molecular chaperone protein for estrogen receptor (ER)-alpha36, a membrane-based variant of ER-alpha. SNCG bound to ER-alpha36 in the presence and absence of functional molecular chaperone heat shock protein 90. Disruption of heat shock protein 90 with 17-AAG significantly reduced ER-alpha36 expression and membrane-initiated estrogen signaling. However, expression of SNCG prevented ER-alpha36 degradation and completely recovered 17-AAG-mediated down-regulation of estrogen signaling. The function of SNCG in ER-alpha36-mediated estrogen signaling is consistent with its ability to stimulate cell growth in response to estrogen. Expression of SNCG also renders tamoxifen resistance, which is consistent with the clinical observation on the association of ER-alpha36 expression and tamoxifen resistance. The present study indicates that ER-alpha36 is a new member of the ER-alpha family that mediates membrane-initiated estrogen signaling and that SNCG can replace the function of heat shock protein 90, chaperone ER-alpha36 activity, stimulate ligand-dependent cell growth, and render tamoxifen resistance.
American Journal Of Pathology 08/2010; 177(2):964-73. · 4.89 Impact Factor
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Tian-Song Xia,
Jue Wang,
Hong Yin, Qiang Ding,
Yi-Fen Zhang,
Hai-Wei Yang,
Xiao-An Liu,
Min Dong,
Qing Du,
Li-Jun Ling,
Xiao-Ming Zha,
Wei Fu,
Shui Wang
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ABSTRACT: An ideal mouse model should closely mimic a clinical situation. However, for most models available, this is not the case since clinical trials frequently fail to reproduce the highly encouraging therapeutic results obtained from pre-clinical studies performed using mouse models. In this study, in the process of extending the application of our previously established breast tissue-derived orthotopic and metastatic (BOM) model, the human breast cancer cell line MDA-MB-231 failed to exhibit any osteotropic features that differed from previous studies. Our observations suggest that a human tissue-specific microenvironment could be an essential requirement for a successful mouse model of breast cancer. Here, multiple in vivo breast cancer models were used to confirm this hypothesis. Human breast tissue and cancellated bone were transplanted subcutaneously to female severe combined immunodeficiency disease (SCID) mice by different assemblies, to build several mouse models termed 'breast-breast', 'breast-bone', 'bone-bone', 'MFP (mouse mammary fat pad)-bone', and 'MFP-breast' models. Two human breast cancer cell lines, MDA-MB-231 and MDA-MB-231BO, and the mouse breast cancer cell line TM40D were used. All cancer cells were labeled with GFP for gross observation. In addition, transplanted human tissues and various mouse tissues including bone, lung, liver, mesentery were examined microscopically. Based on morphological, immunohistochemical, and enzymohistochemical evidence obtained from several comparative experiments in 'breast-breast', 'breast-bone' and 'bone-bone' models, the BOM model was proved to be feasible and reliable. The organ tropism of the breast cancer cell line, which was derived from a mouse model by intracardiac inoculation in a pure mouse microenvironment, was reconsidered. The behavior of breast cancer cells in the mouse model was altered in response to the varying microenvironment. The results in this study suggest the human tissue-specific micro-environment is most likely an essential requirement in mouse models of breast cancer.
Oncology Reports 07/2010; 24(1):203-11. · 1.84 Impact Factor
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ABSTRACT: ETHNOPHARMACOLOGICAL RELEVANCE: Smilax china L., referred to 'Ba Qia' (or 'Jin Gang Teng') in China, is a small vine that grows in the southern parts of China. The roots and tubers of S. china L. have been applied not only as traditional Chinese medicine (TCM) for treatment of diuretic, rheumatic arthritic, detoxication, lumbago, gout, tumor, and inflammatory diseases, but also as food in some area of China. AIM OF STUDY: To investigate the breast tumor cell toxic components in S. china L. continuously and systematically. MATERIALS AND METHODS: Three fractions and six polyphenols were isolated from roots and tubers of S. china L. under bioassay-guided screenings. The structures of six compounds were elucidated by spectroscopic methods and comparison with published data. Their breast tumor cytotoxicity and apoptosis of purified components were performed. RESULTS: Six polyphenols were obtained on the basis of a bioassay-guided separation of the ethyl acetate extract, and their breast tumor cytotoxic activities were tested. They showed anti-tumor activities against MCF-7 and MDA-MB-231 with IC50 value of 2.1-38.9mug/mL, and can induce apoptosis for MCF-7 and MDA-MB-231. CONCLUSIONS: Among these six polyphenols, five (1, 3-6) were reported for the 1st time with in vitro activities on anti-breast tumor cell. It is likely that these polyphenols are the active components of S. china L. responsible for the anti-breast tumor cell activities.
Journal of ethnopharmacology 05/2010; · 2.32 Impact Factor
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ABSTRACT: The roots and rhizomes of Clematis are commonly used as an analgesic, abirritative, antibacterial, antiphlogistic, anticancer and diuretic agent. The Naxi people traditionally used Clematis ganpiniana's (Lévl. Et Vant.) as a diuretic agent, an anti-inflammatory and anticancer remedy.
To investigate the cytotoxic and antibacterial components from Clematis ganpiniana.
The aboveground part of Clematis ganpiniana was isolated by chromatographic techniques. Structures of isolated compounds were identified by spectroscopic methods and comparison with published data. Their cytotoxic, apoptosis and antibacterial activities of purified components were also performed.
By bioassay-guided fractionation techniques and chemical characterization, four triterpene glycosides were isolated and their cytotoxicity against cancer cells and antibacterial activity were tested. They showed significant inhibitory activities against MCF-7, MDA-MB-231 with IC50 value of 0.7-16.5 microg/ml, and significant apoptosis for MCF-7 and MDA-MB-231. Moreover, compound 4 showed weak wide-spectrum antibacterial activity.
These results provide promising baseline information for the potential use of Clematis ganpiniana as well as some of the isolated compounds in the treatment of cancer and infectious disease.
Journal of ethnopharmacology 09/2009; 126(3):382-5. · 2.32 Impact Factor
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ABSTRACT: The studies of breast cancer heavily rely on the availability of experimental animal models. An ideal model of breast cancer is not only required to mimic the whole processes of tumor progress and metastasis, but also required to provide a normal human mammary microenvironment for the breast cancer cells to proliferate and metastasize. Numerous mouse models have been introduced in the literature but failed to achieve the two requirements simultaneously. In this study, we developed a novel human breast tissue-derived orthotopic and metastatic (BOM) mouse model of breast cancer, in which the normal human breast tissues were implanted subcutaneously to create a normal human mammary microenvironment, after which the human breast cancer cells were inoculated into the implants. The BOM model not only mimicked the whole processes of tumor progress and metastasis, but also allowed the orthotopic human breast cancer cells to proliferate in the normal human mammary microenvironment, and finally metastasize preferentially to the distant human tissues. Consequently, the BOM model contributed to the orthotopic tumor formation of 100% (11/11) and the metastatic tumor formation of 72.7% (8/11).
Breast Cancer Research and Treatment 05/2009; 120(2):337-44. · 4.43 Impact Factor
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ABSTRACT: A satisfactory animal model of breast cancer metastasizing to bone is unavailable. In this study, we used human breast cancer stem-like cells and human bone to build a novel "human-source" model of human breast cancer skeletal metastasis.
Human breast cancer stem-like cells, the CD44+/CD24-/lower subpopulation, was separated and cultured. Before injection with the stem-like cells, mice were implanted with human bone in the right or left dorsal flanks. Animals in Groups A, B, and C were injected with 1 x 10(5), 1 x 10(6) human breast cancer stem-like cells, and 1 x 10(6) parental MDA-MB-231 cells, respectively. A positive control group (D) without implantation of human bone was also injected with 1 x 10(6) MDA-MB-231 cells. Immunohistochemistry was performed for determination of CD34, CD105, smooth muscle antibody, CD44, CD24, cytokine, CXC chemokine receptor-4 (CXCR4), and osteopontin (OPN). mRNA levels of CD44, CD24, CXCR4, and OPN in bone metastasis tissues were analyzed by real-time quantitative polymerase chain reaction (PCR).
Our results demonstrated that cells in implanted human bones of group B, which received 1 x 10(6) cancer stem-like cells, stained strongly positive for CD44, CXCR4, and OPN, whereas those of other groups showed no or minimum staining. Moreover, group B had the highest incidence of human bone metastasis (77.8%, P = 0.0230) and no accompaniment of other tissue metastasis. The real-time PCR showed an increase of CD44, CXCR4, and OPN mRNA in metastatic bone tissues in group B compared with those of groups C and D, however the expression of CD24 mRNA in group B were the lowest.
In the novel "human source" model of breast cancer, breast cancer stem-like cells demonstrated a higher human bone-seeking ability. Its mechanism might be related to the higher expressions of CD44, CXCR4, and OPN, and the lower expression of CD24 in breast cancer stem-like cells.
Chinese medical journal 11/2008; 121(20):1980-6. · 0.86 Impact Factor