OBJECTIVE: To investigate the effect of Chaihu Guizhi Decoction (CHGZD) combined with capecitabine on growth and apoptosis of subcutaneous triple-negative breast cancer xenografts in nude mice and explore the possible mechanism. METHODS: Nude mouse models bearing subcutaneous triple-negative breast cancer xenografts were randomized into 6 groups (n=10) for treatment with distilled water (model group), low (10.62 g/kg), medium (21.23 g/kg) and high (42.46 g/kg) doses of CHGZD, capecitabine (0.2 mg/kg), or the combination of CHGZD (42.46 g/kg) and capecitabine (0.2 mg/k) once daily for 21 consecutive days. The general condition of mice was observed, and after 21-day treatments, the tumors were dissected for measurement of tumor volume and weight and histopathological examination with HE staining. Serum IL-6 levels of the mice were determined with enzyme-linked immunosorbent assay (ELISA), and the expression levels of IL-6, STAT3, p-STAT3, Bax, Bcl-2 and cyclin D1 in the tumor tissues were detected using real-time PCR and Western blotting. RESULTS: Compared with those in the model group, the tumor-bearing mice receiving treatments with CHGZD showed significantly increased food intake with good general condition, sensitive responses, increased body weight, and lower tumor mass (P < 0.01). Compared with capecitabine treatment alone, treatment with CHGZD alone at the medium and high doses and the combined treatment all resulted in significantly higher tumor inhibition rates (P < 0.01), induced obvious tumor tissue degeneration and reduced the tumor cell density. Treatments with CHGZD, both alone and in combination with capecitabine, significantly decreased serum IL-6 level, lowered the mRNA expression levels of IL-6 and STAT3, the protein expressions of IL-6, STAT3 and P-STAT3 (P < 0.05), and the mRNA and protein expressions of Bcl-2 and cyclin D1 (P < 0.05), and increased the mRNA and protein expressions of Bax in the tumor tissues (P < 0.05). CONCLUSION CHGZD combined with capecitabine can significantly inhibit tumor growth in nude mice bearing triple-negative breast cancer xenografts, the mechanism of which may involve the inhibition of IL-6/STAT3 signaling pathway and regulation of Bax, Bcl-2 and cyclin D1 expressions to suppress tumor cell proliferation and differentiation and induce cell apoptosis.
Animals ; Capecitabine/pharmacology* ; Cyclin D1/metabolism* ; Drugs, Chinese Herbal ; Heterografts ; Humans ; Interleukin-6/metabolism* ; Mice ; Mice, Nude ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; RNA, Messenger/metabolism* ; STAT3 Transcription Factor/metabolism* ; Signal Transduction ; Triple Negative Breast Neoplasms/drug therapy* ; bcl-2-Associated X Protein/metabolism*

OBJECTIVETo investigate the relationship between the expression of thymidine phosphorylase (TP) and the sensitivity of gastric carcinoma to 5-fluorouracil (5-FU) and its prodrugs.

METHODSGastric carcinoma cell line AGS was transfected with recombinant plasmid pEGFP-N1-TP or control plasmid pEGFP-N1 by lipofectamin 2000. The expression of green fluorescence labeled protein was observed under fluorescence microscope. Positive clones AGS-p and AGS-pTP were selected by G418 treatment. Expression of TP protein and mRNA was detected by immunocytochemistry and RT-PCR, respectively. Drug sensitivity to 5-FU and its prodrugs was assessed by MTT assay.

RESULTSCell clones with the expression of green fluorescent protein (AGS-p) and a clone with TP and green fluorescent fusion protein (AGS-pTP) were established. Immunostaining of TP protein was strongly positive in AGS-pTP and negative in AGS-p and AGS. The expression of TP mRNA was significantly higher in AGS-pTP (0.8090 ± 0.0450) than that in AGS (0.0490 ± 0.0046) and AGS-p (0.0610 ± 0.0069; P < 0.01). The sensitivity to doxifluridine and capecitabine in AGS-pTP was significantly increased, as compared with that in AGS-p. IC50 values of AGS-pTP to doxifluridine and capecitabine were estimated 1.7 folds and 2.2 folds as much as that of AGS-p, respectively. The sensitivity to 5-FU was not different between AGS-pTP and AGS-p.

CONCLUSIONSEnhancement of TP expression improves the sensitivity of gastric carcinoma cells to doxifluridine and capecitabine. But it does not affect the sensitivity to 5-FU.

Antimetabolites, Antineoplastic ; pharmacology ; Capecitabine ; Cell Line, Tumor ; drug effects ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Floxuridine ; pharmacology ; Fluorouracil ; analogs & derivatives ; pharmacology ; Humans ; Plasmids ; RNA, Messenger ; metabolism ; Recombinant Proteins ; genetics ; metabolism ; Sensitivity and Specificity ; Stomach Neoplasms ; metabolism ; pathology ; Thymidine Phosphorylase ; biosynthesis ; genetics ; Transfection

OBJECTIVETo evaluate the efficacy and toxicity of docetaxel and capecitabine combination in the treatment of anthracycline-resistant advanced breast carcinoma.

METHODSForty-three patients with anthracycline-resistant advanced breast carcinoma were treated with docetaxel combined with capecitabine between January 2002 and November 2004. Docetaxel was administered intravenously at a dose of 75 mg/m(2) on D1, and oral intake of capecitabine at a dose of 1600 mg/d on D1 to D14, every 21 days as a cycle. The median number of cycles was 4 (range, 4 approximately 6 cycles).

RESULTSAll the 43 patients had a mean follow-up of 15 months. The overall response rate was 62.8%, with a complete response rate of 20.9% and partial response rate of 44.2%. The median survival time was 15 months with a median time to progression of 7.5 months. The one-year and 2-year survival rates were 62.8% and 41.9%, respectively. The quality of life was improved in all patients. The major toxicity and adverse effects were gastrointestinal reaction and hematological toxicity.

CONCLUSIONThe combination of docetaxel and capecitabine for the treatment of anthracycline-resistant advanced breast carcinoma is effective, safe and tolerable.

Adult ; Aged ; Agranulocytosis ; chemically induced ; Anthracyclines ; pharmacology ; Antimetabolites, Antineoplastic ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; surgery ; Capecitabine ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Drug Resistance, Neoplasm ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; Follow-Up Studies ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Mastectomy ; methods ; Middle Aged ; Neoplasm Recurrence, Local ; Quality of Life ; Remission Induction ; Survival Rate ; Taxoids ; administration & dosage ; adverse effects ; Vomiting ; chemically induced

OBJECTIVETo evaluate the efficacy and safety of docetaxel and capecitabine combination chemotherapy (DC regimen) for patients with anthracycline-resistant metastatic breast cancer.

METHODSThirty-two patients with anthracycline-resistant metastatic breast cancer were treated with a docetaxel and capecitabine combination regimen. All patients received oral administration of capecitabine at a dose of 1250 mg/m(2) twice daily, within 30 min after meal on D1 to D14, and intravenous infusion of docetaxel at a dose of 75 mg/m(2) on D1. The regimen was repeated every 3 weeks.

RESULTSA total of 126 cycles of DC regimen were administered in the 32 cases, with a median of 4 cycles. The overall response rate was 46.9%. Among the 32 patients, there were complete response in 1, partial response in 14, stable disease in 11 and progressive disease in 6 cases. The median time to progression (TTP) was 5.6 months. The one-year survival rate was 56.3%. The effective cases in different metastatic organs were: 8 cases in the lung, 6 cases in the liver, 3 cases in the soft tissue and 3 cases in the lymph nodes. The common adverse reactions were myelosuppression, hand-foot syndrome, nausea and vomiting. Neutropenia was observed in 84.4% of the patients. Two patients developed degree IV myelosuppression.

CONCLUSIONThe combination chemotherapy regimen of docetaxel plus capecitabine is well-tolerated and effective for anthracycline-resistant metastatic breast cancer.

Adult ; Aged ; Anthracyclines ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Capecitabine ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Disease Progression ; Drug Resistance, Neoplasm ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; Humans ; Lung Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Middle Aged ; Remission Induction ; Survival Rate ; Taxoids ; administration & dosage ; adverse effects