[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND AIMS:: To determine the efficacy and toxicity of an oxaliplatin-based regimen as a neoadjuvant chemotherapy setting in triple-negative local advanced breast cancer (TNLABC) patients. METHODS:: Patients with stage IIIb or IIIc, chemotherapy-naive TNLABC receive docetaxel 75 mg/m day 1 and oxaliplatin 130 mg/m day 2, every 21 days for up to 4 cycles. The primary end point is pathologic complete response (CR), and the secondary end points are clinical response (including CR and partial response), disease-free survival, overall survival, and safety. RESULTS:: Twenty-nine TNLABC patients were treated: 17(58.62%) had stage IIIB disease and 12 (41.38%) had stage IIIC disease. After neoadjuvant chemotherapy, there were 10 patients (34.48%) with pathologic CR (95% confidence interval, 21.51%-48.70%). Twenty patients responded (7 CR and 13 partial response) with a 68.97% total clinical response rate (95% confidence interval 57.51%-88.02%). Nearly 27.59% patients (8 patients) had disease progression after at least 2 cycles of chemotherapy, and only 1 patient (3.45%) had the disease stable, respectively. In the 29 treated patients, there were no unusual or unexpected adverse events in a total of 91 cycles for the chemotherapy setting. Common grade 3 or 4 hematologic toxicities were leukocytopenia, which occured in 4 TNLABC patients (13.79%), and thrombocytopenia in 1 patient (3.45%). Grade 3 or 4 transaminase elevation occured in 5 (17.24%) patients and grade 3 vomiting occured in 1(3.45%) patient. One patient experienced grade 3 neurosensory toxicities. There are 5 reports (17.24%) of grade 3 fatigue. CONCLUSIONS:: The results of this phase II clinical study suggest that docetaxel combined with oxaliplatin as a neoadjuvant chemotherapy regimen in TNLABC patients is active and well tolerated, and should be further investigated as a favorable treatment alternative for TNLABC patients. A large randomized prospective clinical study is warranted to confirm the results.
American journal of clinical oncology 08/2012; · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: microRNAs (miRNAs) have been reported to be associated with the pathogenesis and progression of breast cancer. However, little
is known about the pathways through which miRNAs regulate these processes, e.g., the interaction between miRNAs and their
target genes with regard to different pathological status of breast cancer, such as histological grades. This study investigated
the possible roles of miRNAs in the differentiation of histological grades of breast cancer with a computational approach.
Based on a microarray dataset, 15 candidate miRNAs were identified, whose predicted target genes are enriched as differentially
expressed between grade I and grade III breast tumors. Among them, 9 key miRNAs focalize their target genes on 6 central signaling
pathways. The SMAD7 protein, the main inhibitory protein in the TGF-β pathway, is predicted as a target of several miRNAs
and is also regulated by several other pathways that are possibly targeted by miRNAs. It was hypothesized that miRNAs participate
in the differentiation of breast cancer and the TGF-β pathway acts as a major implementary pathway on which several miRNAs
take effect through multiple channels. The prediction power of the predicted miRNA target genes was validated on three independent
datasets. The differential expression of three miRNAs was validated by real-time PCR on breast carcinoma samples of 10 patients.
KeywordsmicroRNA-breast cancer-TGF-β pathway-histological grade
Chinese Science Bulletin 04/2010; 55(10):927-936. · 1.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the effects of suberoyl bis-hydroxamic acid (SBHA), an inhibitor of histone deacetylases, on the apoptosis of MCF-7 breast cancer cells.
Apoptosis in MCF-7 cells induced by SBHA was demonstrated by flow cytometric analysis, morphological observation, and DNA ladder. Mitochondrial membrane potential (DeltaPsim) was measured using the fluorescent probe JC-1. The expressions of p53, p21, Bax, and PUMA were determined using RT-PCR or Western blotting analysis after the MCF-7 cells were treated with SBHA or p53 siRNA.
SBHA induced apoptosis in MCF-7 cells. The expressions of p53, p21, Bax, and PUMA were induced, and DeltaPsim collapsed after treatment with SBHA. p53 siRNA abrogated the SBHA-induced apoptosis and the expressions of p53, p21, Bax, and PUMA.
The activation of the p53 pathway is involved in SBHA-induced apoptosis in MCF-7 cells.
[Show abstract][Hide abstract] ABSTRACT: Gene chip technology was used to determine the gene expression profiles in apoptotic K562 cells induced by homoharringtonine. The expression of forty-four mRNAs was found to be changed significantly were identified after screening with a gene chip capable of detecting 14,218 different human mRNA species simultaneously. Of these genes, 17 were up-regulated and 27 were down-regulated. Most of them were found to be related to apoptosis, oncogenes, or tumor suppression. Several genes with altered gene expression, such as human transforming growth factor-beta inducible early protein gene (TIEG), vitamin D3 upregulated protein 1 gene (VDUP1), RNA binding motif protein 4 gene (RBM4) and v-myc myelocytomatosis viral oncogene homolog (C-MYC), were confirmed by Northern blot analysis. According to the dynamic gene expression pattern in these apoptotic cells, the activated transforming growth factor-beta and tumor necrosis factor signaling pathways play an important role in homoharringtonine-induced apoptosis. TIEG was significantly altered after apoptosis induction, it should be critical for apoptosis signal transmission.
[Show abstract][Hide abstract] ABSTRACT: To better understand the molecular mechanisms underlying breast cancer metastasis and search for potential markers for metastatic progression, we have developed a highly metastatic variant of human MDA-MB-435 breast cancer cell line through in vivo stepwise selection of pulmonary metastatic cells caused by parental MDA-MB-435 cells in the athymic mice. Comparative proteomic analysis using 2-DE and LC-IT-MS revealed that 102 protein spots were reproducibly altered more than three-fold between the selected variant and its parental counterpart. Eleven differentially expressed protein spots were identified with high confidence using SEQUEST with uninterpreted tandem mass raw data. Cathepsin D precursor, peroxiredoxin 6 (PDX6), heat shock protein 27 (HSP27), HSP60, tropomyosin 1 (TPM1), TPM2, TPM3, TPM4, 14-3-3 protein epsilon, and tumor protein D54 were up-regulated in the highly metastatic variant, whereas alpha B-crystalline (CRAB) was only detected in its parental counterpart. Differential expression was confirmed for four proteins including PDX6, CRAB, TPM4, and HSP60 by real-time quantitative PCR and Western blotting analysis in our model. Immunohistochemical analysis in 80 breast cancer donors demonstrated a significant association of TPM4 (p = 0.002), HSP60 (p = 0.001), PDX6 (p = 0.002) but not CRAB (p = 0.113) staining with the presence of lymph node metastasis. In addition, TPM4 staining was also associated with clinical stage (p = 0.000), but no significant association was found between TPM4, PDX6, CRAB, and HSP60 expression and tumor size, hormone receptor, and HER-2 status (p > 0.05). The functional implication of these identified proteins was also discussed. These proteomic data are valuable and informative for understanding breast cancer metastasis and searching for potential markers for metastatic progression.