Breast Neoplasms ; drug therapy ; genetics ; pathology ; Carcinoma, Ductal, Breast ; drug therapy ; genetics ; pathology ; Carcinoma, Lobular ; drug therapy ; genetics ; pathology ; Cell Nucleus ; pathology ; Female ; Gene Expression Profiling ; Humans ; Immunophenotyping ; Lymphatic Metastasis ; Lymphatic Vessels ; pathology ; Neoadjuvant Therapy ; Tumor Burden

OBJECTIVETo explore the effect and clinical significance of Fuzheng Yiliu Granule (FYG) on nuclear transcriptional factor-kappa B (NF-kappa B) and cell cycle in breast tumor.

METHODSFifty-five patients of breast carcinoma were randomly divided into the treated group and the control group, both were treated with conventional chemotherapy, but to the treated group, FYG was given additionally by oral taking. Operation was performed one month later to take out the tumor tissue for detecting NF-kappa B expression and ration of cells in different phases of cell cycle.

RESULTSCompared with the control group, NF-kappa B expression was significantly increased in the treated group, accompanied with increased G0/1 phase cell proportion and decreased S phase cell proportion as well as significantly reduced cell proliferation index (all P < 0.01).

CONCLUSIONFYG could enhance the expression of NF-kappa B in breast tumor tissue, raise the proportion of G0/1 phase cells, decrease proportion S phase cells and reduce the cell proliferation index, showing an active action on the patients prognosis.

Adult ; Aged ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; Cell Cycle ; drug effects ; Cell Division ; drug effects ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Middle Aged ; NF-kappa B ; biosynthesis ; genetics ; Phytotherapy

Cytokines are believed to be involved in a "vicious circle" of progressive interactions in bone metastasis. Iguratimod is a novel anti-rheumatic drug which is reported to have the capability of anti-cytokines. In this study, a rat model was constructed to investigate the effect of iguratimod on bone metastasis and it was found that iguratimod alleviated cancer-induced bone destruction. To further explore whether an anti-tumor activity of iguratimod contributes to the effect of bone resorption suppression, two human breast cancer cell lines MDA-MB-231 and MCF-7 were studied. The effect of iguratimod on tumor proliferation was detected by CCK-8 assay and flow cytometry. The effects of iguratimod on migration and invasion of cancer cells were determined by wound-healing and Transwell assays. Results showed that high dose (30 μg/mL) iguratimod slightly suppressed the proliferation of cancer cells but failed to inhibit their migration and invasion capacity. Interestingly, iguratimod decreased the transcription level of IL-6 in MDA-MB-231 cells in a concentration-dependent manner. Moreover, iguratimod partially impaired NF-κB signaling by suppressing the phosphorylation of NF-κB p65 subunit. Our findings indicated that iguratimod may alleviate bone destruction by partially decreasing the expression of IL-6 in an NF-κB-dependent manner, while it has little effect on the tumor proliferation and invasion.
Animals ; Apoptosis ; drug effects ; Bone Neoplasms ; complications ; drug therapy ; pathology ; secondary ; Bone Resorption ; complications ; drug therapy ; pathology ; Breast Neoplasms ; complications ; drug therapy ; genetics ; pathology ; Carcinogenesis ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Chromones ; administration & dosage ; Female ; Humans ; Interleukin-6 ; biosynthesis ; genetics ; MCF-7 Cells ; Neoplasm Invasiveness ; genetics ; pathology ; Rats ; Sulfonamides ; administration & dosage ; Transcription Factor RelA ; biosynthesis ; genetics

PURPOSE: Bone is the most frequent site of metastasis among breast cancer patients. We investigated prognostic factors affecting survival following bone-only metastasis in breast cancer patients. MATERIALS AND METHODS: The medical records of breast cancer patients who were treated and followed at Gangnam Severance Hospital retrospectively reviewed to identify patients with bone-only metastasis. RESULTS: The median time from the diagnosis of bone-only metastasis to the last follow-up or death was 55.2 [95% confidence interval (CI), 38.6-71.9] months. The Kaplan-Meier overall survival estimate at 10 years for all patients was 34.9%. In the multivariate Cox regression model, bisphosphonate treatment [hazard ratio=0.18; 95% CI, 0.07-0.43], estrogen receptor positivity (hazard ratio=0.51; 95% CI, 0.28-0.94), and solitary bone metastasis (hazard ratio=0.32; 95% CI, 0.14-0.72) were significantly associated with longer overall survival in the bone-only recurrence group. Among the treatment modalities, only bisphosphonate treatment was identified as a significant prognostic factor. CONCLUSION: Identifying the factors influencing breast cancer mortality after bone-only metastasis will help clarify the clinical course and improve the treatment outcome for patients with breast cancer and bone-only metastasis. Bisphosphonates, as a significant prognostic factor, warrant further investigation.
Adult ; Antineoplastic Agents/therapeutic use ; Bone Neoplasms/drug therapy/genetics/*secondary ; Breast Neoplasms/drug therapy/genetics/*pathology ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Prognosis ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Regression Analysis ; Retrospective Studies ; Survival Analysis

OBJECTIVETo study the effect of Shugan Shuru Granule (SSG) on the p53 gene expression in patients with hyperplastic disease of breast (HDB) to indirectly explore the mechanism of SSG's effect on HDB on the molecular pathological level.

METHODSSixty-six patients with HDB were allocated in the treated group and the control group, with the former treated with SSG and the latter not. All patients underwent breast operation and their diseased mammary tissues were cut out, sectioned, and observed under microscopy with HE staining and immunohistochemical staining, with ABC method adopted to estimate the degree of hyperplasia and p53 gene expression. The severity of HDB was classified into normal, mild, moderate and severe grades (marked as 0 to III), according to the degree of hyperplasia in the mammary gland.

RESULTSHyperplasia in the control group mostly belonged to grade I-III before treatment, showing overgrowth of gland and proliferation of glandular epithelial cells, which were high columnar shaped, more stratified, with papillary or substantive dysplasia. While in the treated group, most belonged to grade 0-I after SSG treatment, with proliferated gland and dysplasia recovered to normal or disappeared. The positive rate of p53 gene expression in the treated group was 9.09%, and in the control group 39.39%, comparison between the two groups showing significant difference (P < 0.01), the intensity in the former was significantly weaker than that in the latter.

CONCLUSIONSSG could not only inhibit the proliferation of mammary duct epithelia and lobuli, but also inhibit the over-expression of P53. Therefore, it could be regarded as an effective remedy for treatment of HDB and prevention of mammary cancer genesis.

Adult ; Breast Diseases ; drug therapy ; pathology ; surgery ; Breast Neoplasms ; prevention & control ; Drugs, Chinese Herbal ; administration & dosage ; Epithelium ; pathology ; physiology ; Female ; Gene Expression ; drug effects ; Humans ; Hyperplasia ; Mammary Glands, Human ; pathology ; physiology ; Middle Aged ; Tumor Suppressor Protein p53 ; genetics

OBJECTIVETo stably reverse the multidrug resistance (MDR) of breast carcinoma cells in vitro.

METHODSTwo anti-mdr-1 ribozyme plasmids, RZ196 and RZ179, were constructed with EGFP as reporter gene and transfected into drug-resistant breast carcinoma cells in vitro. The expression of EGFP was observed by laser confocal microscopy. Flow cytometry, RT-PCR and Rhodamine123 efflux assay were used to detect P-glyco protein (p-gp) and mdr-1 mRNA.

RESULTSAfter transfection with RZ196 and RZ179, the mdr-1 indices were reduced from 2.20 to 0.76 and 1.40, the expression rates of p-gp were reduced from 55.0% to 4.6% and 18.2%, the fluorescence intensity increased from 22.0% to 46.2% and 70.1%, TCL reduced from 75% to 28% and 43% respectively. In addition, the expression of ribozyme plasmid in tumor cells was stable under G418 selection. After two months, the mdr-1 indices remained at 0.81 and 1.47 in the cells transfected RZ196 and RZ179 respectively. The expression rates of p-gp were 5.2% and 19.5% and the Rh123 fluorescence intensity was 51.4% and 71.6% respectively.

CONCLUSIONSBoth anti-mdr-1 ribozyme RZ196 and RZ179 can stably reverse MDR phenotype of breast carcinoma cells in vitro. RZ196 construct appears to be more effective.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; genetics ; pathology ; therapy ; Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Gene Transfer Techniques ; Genes, MDR ; genetics ; Genetic Vectors ; Humans ; RNA, Catalytic ; genetics ; Retroviridae ; genetics

OBJECTIVETo investigate the relationship between HER-2 expression and the efficacy of neoadjuvant chemotherapy in local advanced breast cancer.

METHODSDifferent neoadjuvant chemotherapy regimens, namely CMF, CEF, and NEF, were administered in 132 patients with local advanced breast cancer for 2 cycles, each lasting for 28 days. According to the criteria recommended by WHO, the efficacy and safety of the regimens were evaluated after two cycles of neoadjuvant chemotherapy. HER-2 expression was examined by immunohistochemistry using specific monoclonal antibodies before chemotherapy and after surgery.

RESULTSThe overall response rate (RR) of CMF, CEF, and NEF regimens were 39.5% (17/43), 54.3% (25/46) and 72.1% (31/43), with incidence of leukopenia of 34.9% (15/43), 58.7% (27/46) and 60.5% (26/43), respectively. Other adverse effects including decreased hemoglobin (Hb) level, thrombocytopenia, gastrointestinal irritation and alopecia were similar between the 3 groups (P>0.05). No significant variation in HER-2 expression occurred after administration of the 3 regimens. The overall RR to CMF regimen in HER-2-negative breast cancer patients was significantly higher than that in HER-2-positive patients, but showed no significant difference with CEF and NEF regimens.

CONCLUSIONHER-2 expression is not decreased after neoadjuvant chemotherapy in breast cancer patients, and HER-2-positive breast cancer can be resistant to CMF regimen, but not to CEF and NEF regimens.

Adult ; Aged ; Breast Neoplasms ; drug therapy ; genetics ; pathology ; therapy ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; adverse effects ; methods ; Receptor, ErbB-2 ; metabolism ; Treatment Outcome

To study the effect of the proliferation and apoptosis of Survivin-T34A mutant on breast cancer MCF-7 cell, we adopted the method of cell culture in vitro to observe the proliferation and apoptosis of the cell. In the experiment, MCF-7 cells were randomly divided into three groups and transfected with normal saline, PORF-9-null and Survivin-T34A, respectively. Breast cancer nude mouse models were established to study anti-tumor effect of Survivin-T34A in vivo. The activity of the cells in the Survivin-T34A-transfected group was lower than that in PORF-9-null group. The increase of cell apoptosis was observed under electron microscopy, meanwhile the apoptotic rate was obviously higher than that in PORF-9-null control by flow cytometry. Tumor inhibition effects of the mouse which received the injection of Survivin-T34A intratumoral injection were apparent, and the inhibition ratio was as high as 47.1%. In conclusion, Survivin-T34A mutant has anti-tumor effect through efficiently inhibiting the growth of breast cancer MCF-7 cell and actively promoting apoptosis of cancer cells.
Animals ; Apoptosis ; Breast Neoplasms ; drug therapy ; pathology ; Humans ; Inhibitor of Apoptosis Proteins ; genetics ; pharmacology ; Injections, Intralesional ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Transfection

Metastasis is the leading cause of death in breast cancer patients. However, the mechanisms underlying metastasis are not well understood and there is no effective treatment in the clinic. Here, we demonstrate that in MMTV-PyMT, a highly malignant spontaneous breast tumor model, IL-25 (also called IL-17E) was expressed by tumor-infiltrating CD4 T cells and macrophages. An IL-25 neutralization antibody, while not affecting primary tumor growth, substantially reduced lung metastasis. Inhibition of IL-25 resulted in decreased type 2 T cells and macrophages in the primary tumor microenvironments, both reported to enhance breast tumor invasion and subsequent metastasis to the lung. Taken together, our data suggest IL-25 blockade as a novel treatment for metastatic breast tumor.
Animals ; Antibodies, Neoplasm ; pharmacology ; Antibodies, Neutralizing ; pharmacology ; Breast Neoplasms ; drug therapy ; genetics ; immunology ; CD4-Positive T-Lymphocytes ; immunology ; pathology ; Female ; Humans ; Interleukin-17 ; antagonists & inhibitors ; genetics ; immunology ; Interleukins ; antagonists & inhibitors ; genetics ; immunology ; Macrophages ; immunology ; pathology ; Mammary Neoplasms, Animal ; drug therapy ; genetics ; immunology ; Mice ; Neoplasm Metastasis ; Tumor Microenvironment ; drug effects ; genetics ; immunology

Epigenetic mechanisms, including DNA methylation, are responsible for determining and maintaining cell fate, stably differentiating the various tissues in our bodies. Increasing evidence shows that DNA methylation plays a significant role in cancer, from the silencing of tumor suppressors to the activation of oncogenes and the promotion of metastasis. Recent studies also suggest a role for DNA methylation in drug resistance. This perspective article discusses how DNA methylation may contribute to the development of acquired endocrine resistance, with a focus on breast cancer. In addition, we discuss DNA methylome profiling and how recent developments in this field are shedding new light on the role of epigenetics in endocrine resistance. Hormone ablation is the therapy of choice for hormone-sensitive breast tumors, yet as many as 40% of patients inevitably relapse, and these hormone refractory tumors often have a poor prognosis. Epigenetic studies could provide DNA methylation biomarkers to predict and diagnose acquired resistance in response to treatment. Elucidation of epigenetic mechanisms may also lead to the development of new treatments that specifically target epigenetic abnormalities or vulnerabilities in cancer cells. Expectations must be tempered by the fact that epigenetic mechanisms of endocrine resistance remain poorly understood, and further study is required to better understand how altering epigenetic pathways with therapeutics can promote or inhibit endocrine resistance in different contexts. Going forward, DNA methylome profiling will become increasingly central to epigenetic research, heralding a network-based approach to epigenetics that promises to advance our understanding of the etiology of cancer in ways not previously possible.
Antineoplastic Agents ; therapeutic use ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; DNA Methylation ; Drug Delivery Systems ; Drug Resistance, Neoplasm ; Epigenesis, Genetic ; physiology ; Epithelial-Mesenchymal Transition ; Estrogen Receptor alpha ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Signal Transduction