[Comparative study of chemosensitivity and efficacy between pirarubicin and epirubicin in breast cancer].

OBJECTIVE: To compare the chemosensitivity of pirarubicin (THP) and epirubicin (EPI) in primary breast cancer (PBC) cells so as to examine their differential chemosensitivity to THP and EPI by CD-DST (collagen gel droplet embedded culture-drug sensitivity test) system; To detect the differences in the short-term clinical efficacy and side effects between TAC (docetaxel + pirarubicin + cyclophosphamide) and TEC (docetaxel + epirubicin + cyclophosphamide) as the neoadjuvant chemotherapy regimens and the long-term clinical efficacy of CAF (cyclophosphamide + pirarubicin + fluorouracil) and CEF (cyclophosphamide + epirubicin + fluorouracil) as the chemotherapy regimens in breast cancer; To evaluate the feasibility of THP as an adjuvant chemotherapeutic regimen in the treatment of breast cancer. METHODS: From January 2008 to January 2009, a total of 129 fresh breast cancer samples were collected. The differential chemosensitivity of cultured PBC cells to THP and EPI was measured by CD-DST test. And 139 cases of PBC patients inIIb-IIIc phase were randomly divided into two groups: TAC and TEC groups. After 4-6 cycles of neoadjuvant chemotherapy, the primary lesion, axillary lymph nodes and side effects were assessed; The clinical data and survival status of 1241 cases of PBC patients treated at our hospital from 2003 to 2006 were collected and divided into CAF and CEF groups according to their chemotherapeutic regimens. Long-term prognosis was compared between two groups. RESULTS: There was no significant difference of chemosensitivity between THP and EPI in PBC cells (P = 0.743); The overall response rate (RR) of neoadjuvant chemotherapy was 87.8%; the clinical objective responses, pathologic complete remission (pCR), clinical complete remission (cCR), clinical partial remission (cPR) and stable disease (SD) of groups TAC and TEC were 88.7%, 11.3%, 28.2%, 60.6%, 11.3% vs 86.8%, 10.3%, 26.5%, 60.3%, 13.2% respectively. There was no significant difference between two groups (P > 0.05). No significant differences existed between two groups in such side effects as leukopenia, thrombocytopenia, constipation, cardiotoxity and hepatorenal dysfunction (P > 0.05). The gastrointestinal reactions of nausea and vomiting was less frequent in the TAC group than that in the TEC group (46.5% vs 66.2%, P = 0.019); There was no significant difference in 5-year disease-free survival rate (79% vs 78%) and overall survival rate between two groups (85% vs 82%, P > 0.05). CONCLUSION: There were no significant differences in chemosensitivity, clinical efficacy of neoadjuvant chemotherapy, side effects or long-term efficacy between THP and EPI. Both pirarubicin and epirubicin may be used as conventional chemotherapy in breast cancer.

Suppression of matrix metalloproteinase-2 via RNA interference inhibits pancreatic carcinoma cell invasiveness and adhesion.

AIM: To investigate the inhibitory effects of RNA interference (RNAi) on expression of matrix metalloproteinase-2 (MMP-2) gene and invasiveness and adhesion of human pancreatic cancer cell line, BxPC-3. METHODS: RNAi was performed using the vector (pGPU6)-based small interference RNA (siRNA) plasmid gene silence system to specifically knock down MMP-2 expression in pancreatic cancer cell line, BxPC-3. Four groups of different specific target sequence in coding region of MMP-2 and one non-specific sequence were chosen to construct four experimental siRNA plasmids of pGPU6-1, pGPU6-2, pGPU6-3 and pGPU6-4, and one negative control siRNA plasmid of pGPU6 (-). MMP-2 expression was measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Cell proliferation and apoptosis were examined by methyl thiazolyl tetrazolium (MTT) and flow cytometry, respectively. The abilities of adhesion and invasion were detected by cell adhesion assay and cell invasion assay using Transwell chambers. RESULTS: The expression of MMP-2 was inhibited and the inhibitory effects of different sequence varied. pGPU6-1 group had the most efficient inhibitory effect, followed by pGPU6-2 and pGPU6-3 groups. Invasiveness and adhesion were more significantly reduced in pGPU6-1, pGPU6-2 and pGPU6-3 groups as compared with pGPU6 (-) and blank control groups. However, no difference concerning cell proliferation and apoptosis was observed after transfection between experiment groups and control groups. CONCLUSION: RNAi against MMP-2 successfully inhibited the mRNA and protein expression of MMP-2 in the pancreatic cancer cell line, BxPC-3, leading to a potent suppression of tumor cell adhesion and invasion without affecting cell proliferation and apoptosis. These findings suggest that the RNAi approach towards MMP-2 may be an effective therapeutic strategy for the clinical management of pancreatic tumor.

Analysis of p53 and vascular endothelial growth factor expression in human gallbladder carcinoma for the determination of tumor vascularity.

AIM: To examine the expression of p53 and vascular endothelial growth factor (VEGF) as well as microvessel count (MVC) and to investigate the role of VEGF as an angiogenic marker and the possible role of p53 in the regulation of angiogenesis in human gallbladder carcinoma. METHODS: Surgically resected specimens of 49 gallbladder carcinomas were studied by immunohistochemical staining for p53 protein, VEGF, and factor VIII-related antigen. VEGF expression and mutant p53 expression were then correlated with Nevin stage, differentiation grade, MVC, and lymph node metastasis. RESULTS: Positive p53 protein and VEGF expressions were found in 61.2% and 63.3% of tumors, respectively. p53 and VEGF staining status was identical in 55.1% of tumors. The Nevin staging of p53- or VEGF-positive tumors was significantly later than that of negative tumors. The MVC in p53- or VEGF-positive tumors was significantly higher than that in negative tumors, and MVC in both p53- and VEGF-negative tumors was significantly lower than that in the other subgroups. CONCLUSION: Our findings suggest that p53-VEGF pathway can regulate tumor angiogenesis in human gallbladder carcinoma. Combined analysis of p53 and VEGF expression might be useful for predicting the tumor vascularity of gallbladder cancer.

Cyclooxygenase-2 promotes angiogenesis by increasing vascular endothelial growth factor and predicts prognosis in gallbladder carcinoma.

AIM: To investigate the relationships between the expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and the degree of vascularization, clinicopathologic feature, survival time of patients with gallbladder carcinomas. METHODS: Sixty-four gallbladder carcinoma specimens were evaluated for COX-2, VEGF expression by immunohistochemical methods. Microvessel counts (MVC) were determined using CD(34). The relationships between COX-2, VEGF expression, CD(34)-stained MVC, clinicopathologic features and survival time were analyzed. The correlations between COX-2 and VEGF expression, CD(34)-stained MVC were also investigated. RESULTS: COX-2, VEGF immunoreactivity were observed in 71.9% (46/64) and 54.7% (35/64) specimens, respectively. The average MVC in 64 cases of gallbladder carcinoma was 57+/-14 per high power vision field. The status of MVC was closely correlated with Nevin staging, tumor differentiation and lymph node metastasis (P<0.01, 0.002, and 0.003, 0.000, respectively). Increased VEGF expression was significantly correlated with tumor differentiation (poorly and moderately>well differentiated, P<0.05, P = 0.016). Clinical stages had no relation with the expression of VEGF (P>0.05, P = 0.612). There was a positive correlation between COX-2 expression and clinical stages. The positive rate of COX-2 was higher in cases of Nevin stages S(4)-S(5) (81.8%) than in those of Nevin stages S(1)-S(3) (50.0%) with a statistical significance (P<0.01, P = 0.009). The expression of COX-2 did not vary with differentiation (P>0.05, P = 0.067). Statistically significant differences were also observed according to lymph node metastasis, COX-2 expression and VEGF expression (P<0.01, 0.000, and 0.001, respectively). There was no relation between VEGF, COX-2 expression, MVC and the age and sex of patients. MVC and VEGF positive rate in the COX-2 positive gallbladder carcinoma tissue was higher than that in the COX-2 negative tissue (P<0.05, 0.000, and 0.032, respectively). Patients with VEGF, COX-2 positive tumors had a significantly shorter survival time than those with negative tumors (P<0.05, 0.004, 0.01, respectively). CONCLUSION: Augmented tumor neovascularization induced by VEGF may be one of the several effects of COX-2 responsible for poor prognosis of human gallbladder carcinoma. COX-2 inhibitor, either in combination therapy with other agents, or for chemoprevention, may be effective via suppression of angiogenesis in this fatal disease.