No abstract available.
Animals ; Female ; Lymphatic Metastasis/*pathology ; Magnetic Resonance Imaging/*methods ; Mammary Neoplasms, Experimental/*pathology

OBJECTIVE: This experiment aims to determine the diagnostic value of diffusion-weighted imaging (DWI) in the differentiation of axillary inflammatory lymph nodes from metastatic lymph nodes in rabbit models in comparison with conventional magnetic resonance imaging (MRI). MATERIALS AND METHODS: Conventional MRI and DWI were performed at 4 weeks after successful inoculation into the forty female New Zealand white rabbits' mammary glands. The size-based and signal-intensity-based criteria and the relative apparent diffusion coefficient (rADC) value were compared between the axillary inflammatory lymph nodes and metastatic lymph nodes, with histopathological findings as the reference standard. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the aforementioned criteria and rADC value in differentiating the axillary inflammatory lymph nodes from metastatic lymph nodes. RESULTS: Thirty-two axillary inflammatory lymph nodes and 46 metastatic ones were successfully isolated and taken into pathological analysis. The differences of the aforementioned criteria between the two groups were not statistically significant (p > 0.05). However, the rADC value of the inflammatory lymph nodes (0.9 +/- 0.14) was higher than that of metastatic ones (0.7 +/- 0.18), with significant difference (p = 0.016). When the rADC value was chosen as 0.80, the area under the ROC curve is greater than all other criteria, and the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for differentiating two groups were 86.2%, 79.3%, 81.2%, 84.2%, and 85.6%, respectively. CONCLUSION: Diffusion-weighted imaging is a promising new technique for differentiating axillary inflammatory lymph nodes from metastatic lymph nodes. Compared with routine magnetic resonance sequences, DWI could provide more useful physiological and functional information for diagnosis.
Animals ; Axilla ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging ; Female ; Inflammation/pathology ; Lymphatic Metastasis/*pathology ; Magnetic Resonance Imaging/*methods ; Mammary Neoplasms, Experimental/*pathology ; ROC Curve ; Rabbits ; Sensitivity and Specificity

OBJECTIVE: Tumor angiogenesis is an important factor for tumor growth, treatment response and prognosis. Noninvasive imaging methods for the evaluation of tumor angiogenesis have been studied, but a method for the quantification of tumor angiogenesis has not been established. This study was designed to evaluate tumor angiogenesis in a rat breast tumor model by the use of a contrast-enhanced ultrasound (US) examination with a second-generation US contrast agent. MATERIALS AND METHODS: The alkylating agent 19N-ethyl-N-nitrosourea (ENU) was injected into the intraperitoneal cavity of 30-day-old female Sprague-Dawley rats. Three to four months later, breast tumors were detected along the mammary lines of the rats. A total of 17 breast tumors larger than 1 cm in nine rats were evaluated by gray-scale US, color Doppler US and contrast-enhanced US using SonoVue. The results were recorded as digital video images; time-intensity curves and hemodynamic parameters were analyzed. Pathological breast tumor specimens were obtained just after the US examinations. The tumor specimens were stained with hematoxylin and eosin (H & E) and the expression of CD31, an endothelial cell marker, was determined by immunohistochemical staining. We also evaluated the pathological diagnosis of the tumors and the microvessel density (MVD). Spearman's correlation and the Kruskal-Wallis test were used for the analysis. RESULTS: The pathological diagnoses were 11 invasive ductal carcinomas and six benign intraductal epithelial proliferations. The MVD did not correlate with the pathological diagnosis. However, blood volume (BV) showed a statistically significant correlation with MVD (Spearman's correlation, p < 0.05). CONCLUSION: Contrast-enhanced US using a second-generation US contrast material was useful for the evaluation of tumor angiogenesis of breast tumors in the rat.
Animals ; Contrast Media ; Ethylnitrosourea ; Female ; Hemodynamics ; Image Enhancement ; Mammary Neoplasms, Experimental/chemically induced/pathology/*ultrasonography ; Neovascularization, Pathologic/*ultrasonography ; Rats ; Rats, Sprague-Dawley

The inhibitory effect of selenium, vitamin E, and BHA on DMBA-induced mammary tumorigenesis in rats was investigated. Dietary vitamin E (200 IU/Kg diet) alone could not reduce the tumor incidence at 25 weeks after DMBA administration (10mg DMBA/rat) when selenium was deficient. Selenium supplementation (2ppm in drinking water) to rats fed a practical diet (0.17 ppm Se) reduced the tumor incidence to 14.3% from 75% at 27 weeks after DMBA administration. Dietary supplementation of BHA (0.75%) also reduced the incidence of DMBA-induced mammary tumor to 42.9% at 27 weeks after DMBA-treatment. Rats fed a diet deficient in both selenium and vitamin E contained significantly lower glutathione peroxidase activity and higher malondialdehyde in muscle. However, supplementation of selenium or BHA to the rats fed a practical diet did not alter the malondialdehyde content and glutathione peroxidase activities in muscle, skin and mammary gland. Dietary selenium increased the tissue selenium level. DMBA-induced mammary tumorigenesis was reduced by antioxidants tested but the anticarcinogenic effect of selenium or BHA seems to be independent of glutathione peroxi-dase activity.
9,10-Dimethyl-1,2-benzanthracene ; Animal ; Antioxidants/pharmacology* ; Butylated Hydroxyanisole/pharmacology ; Female ; Mammary Neoplasms, Experimental/pathology* ; Rats ; Selenium/pharmacology ; Vitamin E/pharmacology

BACKGROUNDOncolytic herpes simplex virus (HSV) vectors can be used for cancer therapy as direct cytotoxic agents, inducers of anti-tumor immune responses, and as expressers of anti-cancer genes. In this study, the efficacy of HSV vectors, G47Delta and NV1023 were examined for the treatment of the human breast cancer.

METHODSHuman breast cancer MDA-MB-435 cells were cultured or implanted subcutaneously in BALB/c nude mice. The cells or tumors were inoculated with G47Delta or NV1023, and cell killing or inhibition of tumor growth determined. Both viruses contained the LacZ gene and expression in infected cells was detected with X-gal histochemistry.

RESULTSG47Delta and NV1023 were highly cytotoxic to MDA-MB-435 cells in vitro at very low multiplicities of infection. X-gal staining of infected tumor cells in vitro and in vivo illustrated the replication and spread of both viruses. G47Delta and NV1023 inoculation inhibited tumor growth and prolonged mouse survival. Both vectors behaved similarly.

CONCLUSIONSOncolytic HSV vectors, G47Delta and NV1023, were extremely effective at killing human breast cancer cells in vitro and in tumor xenografts in vivo. This novel form of cancer therapy warrants further investigation and consideration of clinical application.

Animals ; Female ; Genetic Therapy ; Genetic Vectors ; Humans ; Mammary Neoplasms, Experimental ; pathology ; therapy ; virology ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Simplexvirus ; genetics ; physiology ; Transplantation, Heterologous ; Virus Replication

OBJECTIVETo establish a murine transplant model for bone marrow purging of metastatic breast cancer and to explore the efficiency of Econazole (Ec) as a purging agent.

METHODSMixtures of TSA /Neo breast cancer cells and murine bone marrow cells were transplanted into lethally irradiated mice following purging with Econazole or saline in vitro. The recipient mice were monitored for hematopoietic engraftment, appearance of metastatic nodules in lungs and the overall survival.

RESULTSAll the mice receiving i.v. injection of TSA cells developed metastatic lung nodules. The hematological recovery was not delayed in mice transplanted with Ec purged bone marrow. More importantly, metastatic lung nodules were not seen in Ec treated group and the overall survival was improved.

CONCLUSIONThe purged metastatic breast cancer cell bone marrow transplant model was easily established and reproducible. Ec could be used to purge the bone marrow grafts contaminated with breast cancer cells.

Animals ; Antineoplastic Agents ; pharmacology ; Bone Marrow Purging ; Bone Marrow Transplantation ; Cell Line ; Econazole ; pharmacology ; Female ; Mammary Neoplasms, Experimental ; pathology ; Mice ; Mice, Inbred BALB C

OBJECTIVETo develop a novel thermal treatment modality against metastatic tumor, and to verify the hypothesis that the extent of tumor angiogenesis damage and tumor cell necrosis, accompanied with immune suppression cells relief is deterministic to enhance therapeutic effect in the thermal treatment.

METHODSThe thermal treatment system was developed in our laboratory. The treatment including hyperthermia and alternate treatment, were locally applied to 4T1 murine mammary carcinoma. The extent of tumor necrosis was examined. Further investigations were performed to study the changes of MDSCs in peripheral blood and spleen.

RESULTSThe alternate treatment caused more damage to tumor microvasculature and tumor cell necrosis. Immunosuppression cells significantly reduced in peripheral blood and spleen. Moreover, it highly increased the survival rate of tumor-bearing mice.

CONCLUSIONSThe greatest destruction of primary tumor induced by the alternate treatment led to a relief of immune suppression in tumor bearing mice, and significantly increased therapeutic effect, especially for metastatic tumor.

Animals ; Female ; Hyperthermia, Induced ; methods ; Mammary Neoplasms, Experimental ; immunology ; pathology ; therapy ; Mice ; Mice, Inbred BALB C ; Myeloid Cells ; immunology ; Neoplasm Metastasis

OBJECTIVETo investigate the apoptosis in MA-891 cells induced by different concentrations of As2O3 and to study its influence on the activity of telomerase and telomerase mTERT-mRNA, which provide theoretical and experimental basis for breast carcinoma.

METHODThe MA-891 breast carcinoma cell lines were used as the object. Different concentration of As2O3 was cultivated with MA-891 cells, and the growth inhibition of MA-891 cells was analyzed by MTT. The rate of apoptosis in MA-891 cells was detected by flow cytometry. The telomerase activity was determined by TRAP-PAGE-SILVER staining and was analyzed by specific soft ware. The expression mTERT-mRNA was examined by RT-PCR assay in untreated and As2O3-treated cells.

RESULTAs2O3 could inhibit the growth of MA-891 cells remarkably; the IC50 value of As2O3 for MA-891 was 9.68 micromol x L(-1) and 5.50 micromol x L(-1) respectively during 24,48 h. The percentage of the apoptosis in MA-891 cells was 30.21%, 48.26%, 57.43%, as the cells were treated with 5, 10, 20 micromol x L(-1) As2O3 for 24 hours. Treated with As2O3 for 24 hand 48 h, the telomerase activity of MA-891 cells was inhibited remarkably, which showed obvious time and concentration dependence. The mTERT-mRNA expression of MA-891 cells were significantly inhibited when treated with As2O3 for 24 h and 48h.

CONCLUSIONAs2O3 could remarkably inhibit the growth of MA-891 cells and could promote the apoptosis of the cells. Treated with As2O3, the activities of telomerase and telomerase mTERT-mRNA were inhibited remarkably and were obvious dosage-effect correlation.

Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Mammary Neoplasms, Experimental ; drug therapy ; pathology ; Mice ; Oxides ; pharmacology ; Telomerase ; genetics

OBJECTIVETo investigate spontaneous metastasis, micrometastasis and genetic stability in human breast carcinoma xenografts in nude mice.

METHODSIntact tissue from surgical specimens from breast carcinoma patients was xenografted into nude mice and transplanted from generation to generation. Cells from the xenografts were cultured in vitro and retransplanted into nude mice. Microsatellite DNA in the genome of human breast carcinomas, xenotransplanted tumors and metastases in nude mice were analyzed at three microsatellite loci.

RESULTSThe tumorigenicity of orthotopic xenotransplantation was 88.6% (31/35), with a metastatic rate of 41.9% (13/31). Cells from xenotransplants were successfully cultured in vitro. The taking rate of retransplantation into nude mice and the spontaneous lung metastasis rate were both 100% (10/10). Microsatellite DNA sequences in the genome of xenotransplanted tumors and metastases in nude mice were identical with that of the original human breast carcinoma at three microsatellite loci.

CONCLUSIONSTumorigenicity and metastatic potential can be improved in human breast carcinoma xenografts using intact fresh tumor tissue and orthotopic grafts. Xenotransplanted tumors and tumors after serial passage maintained the genetic stability. The detection of microsatellite DNA may identify micrometastases in a nude mouse model.

Aneuploidy ; Animals ; Breast Neoplasms ; genetics ; pathology ; Cell Division ; Female ; Humans ; Mammary Neoplasms, Experimental ; genetics ; pathology ; Mice ; Mice, Nude ; Microsatellite Repeats ; Neoplasm Metastasis ; Neoplasm Transplantation ; Time Factors ; Transplantation, Heterologous ; Tumor Cells, Cultured

Interferon-γ (IFN-γ) has been used to control cancers in clinical treatment. However, an increasing number of reports have suggested that in some cases effectiveness declines after a long treatment period, the reason being unclear. We have reported previously that long-term IFN-γ treatment induces malignant transformation of healthy lactating bovine mammary epithelial cells (BMECs) in vitro. In this study, we investigated the mechanisms underlying the malignant proliferation of BMECs under IFN-γ treatment. The primary BMECs used in this study were stimulated by IFN-γ (10 ng/mL) for a long term to promote malignancy. We observed that IFN-γ could promote malignant cell proliferation, increase the expression of cyclin D1/cyclin-dependent kinase 4 (CDK4), decrease the expression of p21, and upregulate the expression of cellular-abelsongene (c-Abl) and histone deacetylase 2 (HDAC2). The HDAC2 inhibitor, valproate (VPA) and the c-Abl inhibitor, imatinib, lowered the expression level of cyclin D1/CDK4, and increased the expression level of p21, leading to an inhibitory effect on IFN-γ-induced malignant cell growth. When c-Abl was downregulated, the HDAC2 level was also decreased by promoted proteasome degradation. These data suggest that IFN-γ promotes the growth of malignant BMECs through the c-Abl/HDAC2 signaling pathway. Our findings suggest that long-term application of IFN-γ may be closely associated with the promotion of cell growth and even the carcinogenesis of breast cancer.
Animals ; Carcinogenesis/pathology* ; Cattle ; Cell Cycle Proteins/metabolism* ; Cell Proliferation/drug effects* ; Cell Transformation, Neoplastic/pathology* ; Cells, Cultured ; Epithelial Cells/pathology* ; Female ; Histone Deacetylase 2/metabolism* ; Imatinib Mesylate/pharmacology* ; Interferon-gamma/pharmacology* ; Mammary Glands, Animal/pathology* ; Mammary Neoplasms, Experimental/pathology* ; Proto-Oncogene Proteins c-abl/metabolism* ; Signal Transduction ; Valproic Acid/pharmacology*