Yi Ma

Modulation of expression of P16 and Her2 in rat breast tissues of mammary hyperplasia model by external use of Rupifang Extract

OBJECTIVE To observe the effect of Rupifang Extract in external use on expression of proto-oncogenes her2 and tumor suppression genes p16 in rat breast tissues of mammary hyperplasia model. To explore the mechanisms of Rupifang Extract in external use for preventing and treating mammary hyperplasia. METHODS Thirty virginal female Wistar rats were randomized into 5 groups, 6 in each, A: blank control group; B: model group; C: the low dose group of Rupifang; D: the middle dose group of Rupifang; and E: The high dose group of Rupifang. The mammary hyperplasia rat models were produced by injecting estradiol benzoate and progesterone and irritating by tail nipping. Drug intervention was also launched during the model formation. After 30 days, the expression of her2 and p16 in breast tissues of rats in each group were detected by the SP immunohistochemical method. RESULTS Compared with Blank control group, the expression of her2 in breast tissues in Model group was higher, and the expression of p16 was lower (P < 0.05 or P < 0.01). After intervention with Rupifang Extract, compared with Model group, the expression of her2 in breast tissues in Rupifang groups was lower, and the expression of p16 higher (P < 0.05 or P < 0.01). CONCLUSION The mechanisms of Rupifang Extract in external application for preventing and treating mammary hyperplasia may be reducing the expression of proto-oncogenes her2 and increasing the expression of tumor suppression genes p16.

Eugenol inhibits oxidative phosphorylation and fatty acid oxidation via downregulation of c-Myc/PGC-1β/ERRα signaling pathway in MCF10A-ras cells

Alteration in cellular energy metabolism plays a critical role in the development and progression of cancer. Targeting metabolic pathways for cancer treatment has been investigated as potential preventive or therapeutic methods. Eugenol (Eu), a major volatile constituent of clove essential oil mainly obtained from Syzygium, has been reported as a potential chemopreventive drug. However, the mechanism by which Eu regulates cellular energy metabolism is still not well defined. This study was designed to determine the effect of Eu on cellular energy metabolism during early cancer progression employing untransformed and H-ras oncogene transfected MCF10A human breast epithelial cells. Eu showed dose-dependent selective cytotoxicity toward MCF10A-ras cells but exhibited no apparent cytotoxicity in MCF10A cells. Treatment with Eu also significantly reduced intracellular ATP levels in MCF10A-ras cells but not in MCF10A cells. This effect was mediated mainly through inhibiting oxidative phosphorylation (OXPHOS) complexs and the expression of fatty acid oxidation (FAO) proteins including PPARα, MCAD and CPT1C by downregulating c-Myc/PGC-1β/ERRα pathway and decreasing oxidative stress in MCF10A-ras cells. These results indicate a novel mechanism involving the regulation of cellular energy metabolism by which Eu may prevent breast cancer progression.

Eugenol alleviated breast precancerous lesions through HER2/ PI3K-AKT pathway-induced cell apoptosis and S-phase arrest

Eugenol can be separated from the oil extract of clove bud, and has many pharmacological functions such as anticancer and transdermal absorption. HER2/PI3K-AKT is a key signaling pathway in the development of breast cancer. In this study, 80 μM eugenol could significantly inhibit the proliferation of HER-2 positive MCF-10AT cells and the inhibition rate was up to 32.8%, but had no obvious inhibitory effect on MCF-7 and MCF-10A cells with HER2 weak expression. Eugenol also significantly induced human breast precancerous lesion MCF-10AT cell apoptosis and cell cycle S-phase arrest, but the biological effects nearly disappeared after HER2 over-expression through transfecting pcDNA3.1-HER2. In MCF-10AT cells treated by 180 μM eugenol, the protein expressions of HER2, AKT, PDK1, p85, Bcl2, NF-κB, Bad and Cyclin D1 were decreased and the decreased rates were respectively 63.0%, 60.0%, 52.9%, 62.9%, 37.1%, 47.2%, 61.7%, 59.1%, while the p21, p27 and Bax expression were increased by 4.48-, 4.76- and 2.57-fold respectively. In the rat models of breast precancerous lesion, 1 mg eugenol for external use significantly inhibited the progress of breast precancerous lesion and the occurrence rate of breast precancerous lesions and invasive carcinomas was decreased by about 30.5%. Furthermore eugenol for external (1 mg) markedly decreased the protein expressions of HER2 (62.9%), AKT (58.6%), PDK1 (56.4%), p85 (54.3%), Bcl2 (59.3%), NF-κB (65.7%), Bad (64.0%), Cyclin D1 (43.0%), while p21, p27 and Bax protein expressions were respectively increased 1.83-, 2.52- and 2.51-fold. The results showed eugenol could significantly inhibit the development of breast precancerous lesions by blocking HER2/PI3K-AKT signaling network. So eugenol may be a promising external drug for breast precancerous lesions.Eugenol can be separated from the oil extract of clove bud, and has many pharmacological functions such as anticancer and transdermal absorption. HER2/PI3K-AKT is a key signaling pathway in the development of breast cancer. In this study, 80 μM eugenol could significantly inhibit the proliferation of HER-2 positive MCF-10AT cells and the inhibition rate was up to 32.8%, but had no obvious inhibitory effect on MCF-7 and MCF-10A cells with HER2 weak expression. Eugenol also significantly induced human breast precancerous lesion MCF-10AT cell apoptosis and cell cycle S-phase arrest, but the biological effects nearly disappeared after HER2 over-expression through transfecting pcDNA3.1-HER2. In MCF-10AT cells treated by 180 μM eugenol, the protein expressions of HER2, AKT, PDK1, p85, Bcl2, NF-κB, Bad and Cyclin D1 were decreased and the decreased rates were respectively 63.0%, 60.0%, 52.9%, 62.9%, 37.1%, 47.2%, 61.7%, 59.1%, while the p21, p27 and Bax expression were increased by 4.48-, 4.76- and 2.57-fold respectively. In the rat models of breast precancerous lesion, 1 mg eugenol for external use significantly inhibited the progress of breast precancerous lesion and the occurrence rate of breast precancerous lesions and invasive carcinomas was decreased by about 30.5%. Furthermore eugenol for external (1 mg) markedly decreased the protein expressions of HER2 (62.9%), AKT (58.6%), PDK1 (56.4%), p85 (54.3%), Bcl2 (59.3%), NF-κB (65.7%), Bad (64.0%), Cyclin D1 (43.0%), while p21, p27 and Bax protein expressions were respectively increased 1.83-, 2.52- and 2.51-fold. The results showed eugenol could significantly inhibit the development of breast precancerous lesions by blocking HER2/PI3K-AKT signaling network. So eugenol may be a promising external drug for breast precancerous lesions.

Shenqi Fuzheng Injection Combined with Chemotherapy for Breast Cancer: A Meta-Analysis of Randomized Controlled Trials

Purpose. To evaluate the therapeutic effectiveness and safety of shenqi fuzheng injection (SFI) in the associated chemotherapy of breast cancer. Methods. 1247 subjects were included in this study for meta-analysis with RevMan 5.3. Results. The clinical curative effective rate (OR = 2.03, 95% Cl [1.44, 2.86], P < 0.0001), grades of KPS (OR = 4.11, 95% Cl [2.74, 6.16], P < 0.00001), CD3+ cells (MD = 7.05, 95% Cl [0.45, 13.64], P = 0.04) and CD4+ cells (MD = 8.60, 95% Cl [2.67, 14.54], P = 0.004) and CD4/CD8+ cells (MD = 0.35, 95% Cl [0.14, 0.56], P = 0.001), WBC (OR = 0.30, 95% Cl [0.20, 0.46], P ≤ 0.0001), PLT (OR = 0.36, 95% Cl [0.20, 0.67], P = 0.001), gastrointestinal reaction (OR = 0.21, 95% Cl [0.14, 0.32], P < 0.00001), and ECG (OR = 0.26, 95% Cl [0.13, 0.51], P < 0.0001) in the experimental group were superior to the control group. While there were no differences between two groups in CD8+ (MD = 0.21, 95% Cl [−2.81, 3.23], P = 0.89), NK+ (MD = 1.06, 95% Cl [−9.40, 11.53], P = 0.84), RBC (OR = 0.49, 95% Cl [0.14, 1.74], P = 0.27), liver function (OR = 0.59, 95% Cl [0.28, 1.24], P = 0.16), renal function (OR = 0.56, 95% Cl [0.13, 2.45], P = 0.44), and bone marrow suppression (OR = 0.50, 95% Cl [0.25, 1.01], P = 0.05). Conclusion. SFI combined with chemotherapy, to some extent, can improve the effectiveness and the security in the treatment of breast cancer; the mechanism may be related to the elevated immunity.

Integrative analysis of lncRNAs and miRNAs with coding RNAs associated with ceRNA crosstalk network in triple negative breast cancer

Triple negative breast cancer (TNBC) is a particular subtype of breast malignant tumor with poorer prognosis than other molecular subtypes. Currently, there is increasing focus on long non-coding RNAs (lncRNAs), which can act as competing endogenous RNAs (ceR-NAs) and suppress miRNA functions involved in post-transcriptional regulatory networks in the tumor. Therefore, to investigate specific mechanisms of TNBC carcinogenesis and improve treatment efficiency, we comprehensively integrated expression profiles, including data on mRNAs, lncRNAs and miRNAs obtained from 116 TNBC tissues and 11 normal tissues from The Cancer Genome Atlas. As a result, we selected the threshold with |log2FC|>2.0 and an adjusted p-value >0.05 to obtain the differentially expressed mRNAs, miRNAs and lncRNAs. Hereafter, weighted gene co-expression network analysis was performed to identify the expression characteristics of dysregulated genes. We obtained five co-expression modules and related clinical feature. By means of correlating gene modules with protein–protein interaction network analysis that had identified 22 hub mRNAs which could as hub target genes. Eleven key dysregulated differentially expressed micro RNAs (DEmiRNAs) were identified that were significantly associated with the 22 hub potential target genes. Moreover, we found that 14 key differentially expressed lncRNAs could interact with the key DEmiRNAs. Then, the ceRNA crosstalk network of TNBC was constructed by utilizing key lncRNAs, key miRNAs, and hub mRNAs in Cytoscape software. We analyzed and described the potential characteristics of biological function and pathological roles of the TNBC ceRNA co-regulatory network; also, the survival analysis was performed for each molecule. These findings revealed that ceRNA crosstalk network could play an important role in the development and progression for TNBC. In addition, we also identified that some molecules in the ceRNA network possess clinical correlation and prognosis.

Data mining for points-selection rules in acupuncture treatment of mammary gland hyperplasia

ObjectiveTo explore and analyze the points-selection rules in acupuncture treatment of mammary gland hyperplasia (MGH) by data mining and statistical method.MethodsClinical literatures about the treatment of MGH with acupuncture published in the recent 16 years were retrieved from Chinese Journal Full-text Database (CJFD) and established into a database by Excel. The SPSS 20 version software and Clementine 12.0 version software were adopted to analyze the frequency and association rules of points-selection in the treatment of MGH with acupuncture.ResultsThe top 3 points used most frequently in acupuncture treatment of MGH were Danzhong (CV 17), Taichong (LR 3) and Zusanli (ST 36); points from the Stomach Meridian of Foot Yangming and Liver Meridian of Foot Jueyin were most commonly used; the commonly selected points were predominantly distributed in thoracic and abdominal regions and lower limbs; emphasis on the combination use of local and distal points; of the specific points, the five Shu-Transmitting points were mostly used; association analysis showed that the associations among Taichong (LR 3), Danzhong (CV 17) and Zusanli (ST 36) were the most significant.ConclusionThe data mining results substantially accord with the general rules of acupuncture-moxibustion theories in traditional Chinese medicine, able to reflect the points-selection principles and features in acupuncture treatment of MGH and provide evidence for the points selection in the treatment of MGH in acupuncture clinic.摘要目的运用数据挖掘技术及统计学方法, 分析并挖掘针刺治疗乳腺增生的选穴规律。方法检索中国期 刊全文数据库近16 年针刺治疗乳腺增生的临床文献, 运用Excel 软件建立文献数据库。使用SPSS 20 和Clementine 12.0 软件对针刺治疗乳腺增生腧穴处方进行频数统计分析和关联规则分析。结果针刺治疗乳腺增生腧穴中使 用频次最高的前3 位穴位为膻中、太冲和足三里; 以足阳明胃经、足厥阴肝经穴位选用最多; 常用穴位主要分布 在胸腹部和下肢; 重视局部选穴和远端取穴相配合; 特定穴中五输穴的使用最多; 关联规则分析显示穴位间相关 性最高的是太冲、膻中和足三里。结论数据挖掘的结果与传统医学中针灸治疗理论的一般规律基本相符, 能够 反映针刺治疗乳腺增生病的取穴特点及规律, 为临床针刺治疗乳腺增生病选穴提供依据。

Pharmacodynamics and Medicinal Chemistry of an External Chinese Herbal Formula for Mammary Precancerous Lesions

Ruyan Neixiao Cream (RYNXC) is a traditional Chinese herbal formula for treating mammary precancerous disease. This study was carried out to investigate in vivo anticancer effect of RYNXC and multiple constituents. 32 virginal Sprague-Dawley rats were randomly divided into blank control group (BC), mammary precancer models group (MODEL), tamoxifen group (TAM), and Ruyan Neixiao Cream group (RYNXC). TAM was intervened by tamoxifen; RYNXC was intervened by Ruyan Neixiao Cream. The chromatographic separation was performed by high performance liquid chromatography (HPLC) coupled with mass spectrometry (MS). RYNXC showed significant improvement in erythrocyte aggregation index (EAI), hematocrit (HCT), fibrinogen (FIB), spleen coefficient, and uterus coefficient compared with MODEL. In RYNXC and TAM groups, atypical hyperplasia was observed in pathological mammary tissues; meanwhile in MODEL group, ductal carcinoma was observed in situ. Moreover, fifteen compounds were characterized according to HPLC-MS data, including organic acids, tannin, alkaloid, volatile oil, anthraquinones, and flavonoids. The study suggests that RYNXC was an effective Chinese herbal formula for mammary precancerous lesions and provides a scientific basis for the quality standard and the pharmacology of RYNXC. It will be beneficial to the future clinical application of RYNXC.

The Study of Interference with Ruyanneixiao Cream on Hemorheology and Mammary Microcirculation of Mammary Precancer Rats

Objective: to probe the interference of Ruyanneixiao cream for hemorheology and mammary microcirculation of mammary precancer rats. Methods: 48 virginal female SD rats were randomly allocated into 6 groups, A: Blank control group (8); B: Mammary precancer model group (8); C: Tamoxifen (TAM) group (8); D: High dose group of Ruyanneixiao cream (8); E: Middle dose group of Ruyanneixiao cream (8); F: Low dose group of Ruyanneixiao cream (8). The changes of hemorheology and mammary microcirculation were recorded when the rats were executed after 60d. Result: compared with the Blank control group, the whole blood viscosity and plasma viscosity of mammary precancer model group was higher (P<0.05) and the perfusion of mammary microcirculation was lower (P<0.01). Compared with mammary precancer model group, the hemorheological parameters and perfusion of mammary microcirculation of each dose group of Ruyanneixiao cream were improved (P<0.05). Conclusion: Ruyanneixiao cream can improve the status of hemorheology, increase the perfusion of mammary microcirculation. And it may be one of mechanism to treat and prevent mammary precancer disease.

The Establishing and Applied Research of Animal Models of Mammary Precancerous Lesions

Currently, the methods of establishing mammary precancer animal model is various, including hormones-induced precancerous lesions model, chemical carcinogen precancerous lesions model, precancerous lesions model induced by hormones combined with chemical carcinogen, MCF10AT cell lines transplantation model, transgenic model and disease and syndrome animal model. This paper aims to explore the establishing and applied research of animal models of mammary precancerous lesions. Showing it would play a critical role in studying the cause and pathogenesis of mammary precancerous lesions, effective prevention and improving treatment effect by a proper mammary precancerous lesion animal model.