In the present study, 13 clinical cases of canine mammary adenocarcinoma were evaluated in order to understand the effect of Tarantula cubensis extract (TCE) on tumor tissue. Punch biopsies were taken from the tumors before treatment with TCE. Subcutaneous injections of TCE were administered three times at weekly intervals (3 mL per dog). Between days 7 and 10 after the third injection, the tumor masses were extirpated by complete unilateral mastectomy. Pre- and post-treatment tumor tissues were immunohistochemically assessed. The expression of B-cell lymphoma 2 (Bcl-2) was found to be higher in pre-treatment compared to post-treatment tissues (p < 0.01) whereas Ki-67 expression was lower in post-treatment tissues (p < 0.01). No significant differences in fibroblast growth factor or vascular endothelial growth factor expression were observed between pre- and post-treatment tissues (p > 0.05). The apoptotic index was determined to be low before treatment and increased during treatment. These results suggest that TCE may be effective for controlling the local growth of canine mammary adenocarcinoma by regulating apoptosis.
Adenocarcinoma/*drug therapy/physiopathology ; Animals ; Apoptosis/drug effects ; Dog Diseases/*drug therapy/physiopathology ; Dogs ; Female ; Mammary Neoplasms, Animal/*drug therapy/physiopathology ; Mammary Neoplasms, Experimental/*drug therapy/physiopathology ; Mitosis/drug effects ; Spiders/*chemistry

BACKGROUND: Amplifications of the HER-2/neu oncogene and the Topoisomerase II-alpha gene are important determiners of the response to chemotherapy in the breast cancer. For detecting HER-2/neu amplification, fluorescent in situ hybridization and immunohistochemistry are currently regarded as standard methods. Chromogenic in situ hybridization (CISH) is investigated as a new modification of in situ hybridization. The purpose of this study is to compare the efficacy of CISH and immunohistochemistry (IHC) in detecting HER-2/neu oncogene amplification and to investigate the prognostic significance of the HER-2/neu oncogene and the Topoisomerase II-alpha gene in breast cancer. METHODS: Using CISH and IHC the amplifications and protein expressions of the HER-2/neu oncogene were studied on paraffin sections of 43 infiltrating duct carcinomas. The expression of the Topoisomerase II-alpha gene was studied immunohistochemically. RESULTS: Of the 43 infiltrating duct carcinomas, amplifications of the HER-2/neu oncogene by CISH were observed in 8 cases (18.6%), and the HER-2/neu protein was deemed overexpressed by IHC in 9 cases (20.9%). The amplifications of the HER-2/neu oncogene showed a statistically significant correlation with tumor size, histological grade, and the Topoisomerase II-alpha index. The Topoisomerase II-alpha index showed a statistically significant correlation with tumor size, lymph node status, stage, histologic grade, and estrogen receptor status. CONCLUSIONS: CISH is a useful alternative for determining HER-2/neu amplification, especially for confirming the immunohistochemical staining results. HER-2/neu amplification and the Topoisomerase II-alpha gene index may be prognostic factors of breast cancer.
Animals ; Breast Neoplasms* ; Breast* ; Drug Therapy ; Estrogens ; Immunohistochemistry ; In Situ Hybridization* ; In Situ Hybridization, Fluorescence ; Lymph Nodes ; Mammary Neoplasms, Animal ; Oncogenes* ; Paraffin

OBJECTIVETo study and evaluate the effect of Sangu Decoction (SGD, ) on the bone destruction due to mammary cancer metastasis.

METHODSMetastasis rat mammary tumor-1 cells were transplanted into the left hind limb tibia of SD rats to establish the bone metastasis of the mammary cancer model. The modeled rats were treated with SGD for observing its effect on rats' pain behavior, including 50% paw withdrawal threshold (50% PWT) after von Frey fiber stimulation, burden difference of bilateral feet, and thermal withdrawal latency (TWL), with zoledronic acid as the positive control. Moreover, the damage in the tibia sample of rats was scored by an iconographic method, and the bone mineral density (BMD) as well as the bone mineral content (BMC) were estimated.

RESULTSThe model established showed characteristics of mixed metastasis, revealing the manifestations of tumor development, bone destruction, cancerous pain, etc. In the SGD-treated group, 50% PWT was prolonged (8.13 ± 4.76 vs. 2.30 ± 2.19), and TWL was longer (3.48 ± 0.62 s vs. 2.89 ± 0.26 s) than those in the control group, respectively (P<0.05 or P<0.01). Iconographic scoring also showed improvement of BMD (0.134 ± 0.009 vs. 0.120 ± 0.007, P<0.01) and an elevating trend of BMC in the SGD-treated group.

CONCLUSIONSGD could effectively alleviate the cancerous pain of bone metastasis and mitigate the metastasis that cause osteolytic destruction of bone.

Animals ; Bone Density ; drug effects ; Bone Neoplasms ; drug therapy ; physiopathology ; secondary ; Bone and Bones ; drug effects ; pathology ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Mammary Neoplasms, Animal ; pathology ; Rats ; Rats, Sprague-Dawley ; Reaction Time ; drug effects

Animals ; Antineoplastic Agents, Alkylating/pharmacology* ; Breast Neoplasms/drug therapy* ; Cell Line ; Cell Line, Tumor ; Cyclophosphamide/pharmacology* ; Ginkgo biloba/chemistry* ; Mammary Neoplasms, Animal/drug therapy* ; Mice ; Plant Extracts/administration & dosage*

OBJECTIVETo explore the effect of Yanghe Huayan Decoction (YHD, a representative recipe for warming yang mass dissipating) in inhibiting precancerosis of breast cancer (PBC) and on the protein and mRNA expression of ki67.

METHODSThe PBC rat model was established by dimethylbenzanthracene (DMBA), and 9 weeks later rats were randomly divided into the blank control group, the model group, the YHD group, the Sanjie Huatan Decoction group (SHD), the Pingxiao Tablet group (PT), and the tamoxifen group. Rats in the model group were administered with water by gastrogavage. Rats in the YHD group received YHD (deglued antler powder 12 g, prepared rhizome of rehmannia 9 g, cassia bark 6 g, white mustard seed 3 g, zedoary root 12 g, appendiculate cremastra pseudobulb 15 g, chekiang fritillary bulb 9 g, licorice root 6 g) at the daily dose of 7.2 g/kg by gastrogavage. Rats in the SHD group received SHD (oldenlandia diffusa 15 g, Scutellaria Barbata 15 g, Trichosanthes Kirilowii 15 g, pinellia 9 g) at the daily dose of 5.4 g/kg by gastrogavage. Rats in the PT group received PT at the daily dose of 144 mg/kg by gastrogavage. Those in the tamoxifen group received tamoxifen at the daily dose of 4 mg/kg by gastrogavage. Pathomorphological changes of the breast tissue were observed by HE staining. The positive rate and the gray value of ki67 expression were detected by immunohistochemical assay. And the expression of ki67 mRNA was detected by q-PCR.

RESULTSCompared with the model group, the general hyperplasia and the occurrence rate of precancerous lesion were higher and the occurrence rate of invasive carcinoma was lower in each treatment group (P < 0.05). Except the SHD group, the intensity of ki67 grey value increased in each treatment group (P < 0.05, P < 0.01). Except the PT group, the positive rate of ki67 and mRNA expression of ki67 increased in the rest treatment groups (P < 0.05, P < 0.01). Compared with the YHD group, there was no statistical difference in the occurrence rate of infiltration or the occurrence rate of precancerous lesion (P > 0.05). The positive rate of ki67 expression and mRNA expression of ki67 increased in the PT group, showing statistical difference (P < 0.05).

CONCLUSIONSYHD could partially inhibit and reverse canceration of breast cancer. It also could inhibit ki67 protein and mRNA expression. Its effect was similar to tamoxifen and superior to PT. So it was suitable for prevention and treatment of precancerous lesion of breast cancer.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Ki-67 Antigen ; metabolism ; Mammary Neoplasms, Experimental ; chemically induced ; drug therapy ; metabolism ; Precancerous Conditions ; drug therapy ; metabolism ; Rats ; Rats, Sprague-Dawley

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

OBJECTIVETo explore the effect of ricin temperature response gel on breast cancer and its regulatory effect on immune function in rats.

METHODSRicin was purified by chromatography and identified by immunoblotting. The rat subcutaneously transplanted breast cancer model was established. Forty model rats with a tumor diameter of about 3.0 cm were subjected to the study. They were randomized into four groups equally: the model group and three treated groups (blank gel, ricin, ricin-gel) were administered with blank gel, ricin, and ricin temperature response gel via percutaneous intratumor injection, respectively. The tumor was isolated 10 days later for the estimation of tumor inhibition rate (TIR) by weighing, pathologic examination, and detection of tumor apoptosis-associated genes bcl-2 and bax with semiquantitative RT-PCR. Also, peripheral blood was obtained to test T-lymphocyte subsets, the killing function of lymphocytes, and the contents of tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2). The outcomes were compared between groups.

RESULTSThe TIR in the ricin-gel group was 61.8%, with the pathologic examination showing extensive tumor tissue necrosis. Compared with the model group, after ricin temperature response gel treatment, bcl-2 expression was down-regulated, bax expression was up-regulated, CD4+ lymphocytes and CD4+/CD8+ ratio in peripheral blood were increased, the killing function of lymphocytes was enhanced, and the contents of TNF-α and IL-2 were elevated (P < 0.05 or P < 0.01).

CONCLUSIONIntratumor injection of ricin temperature-responsive gel showed significant antitumor effect on breast cancer and could enhance the immune function in the tumor-bearing rat.

Animals ; Antineoplastic Agents ; administration & dosage ; Apoptosis ; drug effects ; CD4-CD8 Ratio ; Disease Models, Animal ; Female ; Gels ; therapeutic use ; Immunohistochemistry ; Immunomodulation ; drug effects ; Injections, Intralesional ; Interleukin-2 ; immunology ; metabolism ; Mammary Neoplasms, Experimental ; drug therapy ; immunology ; pathology ; Random Allocation ; Rats ; Rats, Wistar ; Ricin ; administration & dosage ; Sensitivity and Specificity ; Temperature ; Tumor Necrosis Factor-alpha ; immunology ; metabolism