Myeloid-Derived Suppressor Cells Recruited by Chemokine (C-C Motif) Ligand 3 Promote the Progression of Breast Cancer via Phosphoinositide 3-Kinase-Protein Kinase B-Mammalian Target of Rapamycin Signaling / 한국유방암학회지

Purpose@#Numerous studies have shown that the frequency of myeloid-derived suppressor cells (MDSCs) is associated with tumor progression, metastasis, and recurrence. Chemokine (C-C motif) ligand 3 (CCL3) may be secreted by tumor cells and attract MDSCs into the tumor microenvironment. In the present study, we aimed to explore the molecular mechanisms whereby CCL3 is involved in the interaction of breast cancer cells and MDSCs. @*Methods@#The expression of CCL3 and its receptors was investigated using real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The cell counting Kit-8, wound healing, and transwell assays were performed to study cell growth, migration, and invasion. Cell cycling, apoptosis, and the frequency of MDSCs were investigated through flow cytometry. Transwell assays were used for co-culture and chemotaxis detection. Markers of the epithelial-mesenchymal transition (EMT) were determined with western blotting. The role of CCL3 in vivo was studied via tumor xenograft experiments. @*Results@#CCL3 promoted cell proliferation, migration, invasion, and cycling, and inhibited apoptosis of breast cancer cells in vitro. Blocking CCL3 in vivo inhibited tumor growth and metastases. The frequency of MDSCs in patients with breast cancer was higher than that in healthy donors. Additionally, MDSCs might be recruited by CCL3. Co-culture with MDSCs activated the phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin (PI3K-Akt-mTOR) pathway and promoted the EMT in breast cancer cells, and their proliferation, migration, and invasion significantly increased. These changes were not observed when breast cancer cells with CCL3 knockdown were co-cultured with MDSCs. @*Conclusion@#CCL3 promoted the growth of breast cancer cells, and MDSCs recruited by CCL3 interacted with these cells and then activated the PI3K-Akt-mTOR pathway, which led to EMT and promoted the migration and invasion of the cells.

Clinical characteristics and prognosis of different subtypes ofbreast cancer with bone metastasis / 西安交通大学学报(医学版)

Objective To analyze the clinicopathological characteristics and prognosis of different subtypes of breast cancer patients with bone metastasis.Methods For this study, we recruited 300 primary breast cancer patients with bone metastasis treated at the Department of Oncology, the First Affiliated Hospital of Xi`an Jiaotong University, between September 1, 2007 and September 1, 2011.We also retrospectively analyzed their clinical and follow-up data.Results The percentage of Luminal A, Luminal B, human epidermal growth factor receptor-2 (HER-2) overexpression and triple negative subtypes in all the bone metastatic breast cancer patients was 59.0％, 16.0％, 13.7％ and 11.3％, respectively.Age, tumor size and histologic grade significantly differed among the four subtypes (P0.05).The median survival time of Luminal A breast cancer patients with bone metastasis was 28.6 months, longer than Luminal B (26.9 months), HER-2 overexpression (20.9 months) and triple negative breast cancer patients (12.0 months) with bone metastasis.The overall survival significantly differed among the patients with four subtypes of breast cancer.Conclusion Different subtypes of breast cancer patients with bone metastasis have different clinical characteristics and prognosis.Luminal A breast cancer patients with bone metastasis have better prognosis whereas triple negative subtype has poorer prognosis.

Efficacy of neoadjuvant chemotherapy combined with bevacizumab versus neoadjuvant chemotherapy alone for Her2-negative breast cancer: a meta-analysis of randomized controlled clinical trials / 浙江大学学报·医学版

To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with bevacizumab versus neoadjuvant chemotherapy alone for Her2-negative breast cancer.We searched PubMed, the Cochrane Library, Web of Science, CNKI, Wanfang Database and the abstracts of major international conferences in recent 5 years to identify prospective randomized controlled clinical trials that met the inclusion and exclusion criteria. Study selection and analyses were undertaken according to the Cochrane Handbook. Meta-analysis was performed using RevMan 5.3 software.Six trials were identified with 4440 eligible patients. The results of this meta-analysis showed that the rate of pathological complete response (pCR) was higher in Her-2 negative breast cancer patients receiving bevacizumab combined with neoadjuvant chemotherapy than that in patients with neoadjuvant chemotherapy alone (24.7% vs 20.1%,=1.23, 95%:1.10-1.37,<0.01). In addition, the pCR rate rose up when bevacizumab was added to neoadjuvant chemotherapy both in hormone receptor-positive patients (13.1% vs 10.2%,=1.28, 95%:1.04-1.58,<0.05) and in hormone receptor-negative patients (46.3% vs 37.1%,=1.25, 95%:1.12-1.39,<0.01). Statistical differences were observed in the rate of relevant adverse events such as hypertention (3.2% vs 0.6%,=5.292, 95%:2.933-9.549,<0.01) and mucositis (10.5% vs 2.0%,=5.340, 95%:3.743-7.617,<0.01) between the combination group and the chemotherapy alone group. Differences in other toxicities such as febrile neutropenia, infection, surgical complications, neutropenia and hand-foot syndrome were also found to be statistically significant between the combination group and the chemotherapy alone group (all<0.05), while such difference was not found in the occurrence of peripheral neuropathy (>0.05).The addition of bevacizumab to neoadjuvant chemotherapy in Her2-negative breast cancer can significantly improve pathological complete response, but may bring more grade 3 and 4 toxicities.More neoadjuvant trials need to be done to define subgroups of Her2-negative breast cancer that would have clinically significant long-term benefit from bevacizumab treatment.

Research on pharmacokinetics of high-dose tamoxifen in non-small cell lung cancer patients / 药物分析学报

Objective To study the pharmacokinetics of tamoxifen at a high dosage, which will offer a theoretical support for an appropriate clinical use of the medicine in non-small cell lung cancer (NSCLC) patients. Methods Three qualified NSCLC patients are selected and given tamoxifen (TAM) 160 mg per Os. Blood samples were collected at different times and then analyzed by high-performance liguid chromatography. The PK-GRAPH program was used to obtain the parameters. Results The concentration-time courses of the TAM 160 mg were fitted to one-compartment model. The pharmacokinetic parameters were estimated as follows: Tmax (6.35±1.24)h, Cmax (217.39±7.71)ng/Ml, AUC (12 127.39±636.16)ng·h/Ml and T1/2ke (34.13±2.97)h. Conclusion TAM 160mg one day per Os cannot reach the effective maintenance concentration in vivo required for reversing MDR in vitro. Loading-maintenance dose strategy is recommended to study the pharmacodynamics of tamoxifen at a high dosage in NSCLC patients.

Correlation between drug resistance of leukemic cells and Caspase-3 / 西安交通大学学报(医学版)

Objective To explore the relationship between drug resistance of leukemic cells and Caspase-3,this study took adriamycin(ADR)-resistant human chronic granulocytic leukemic cell strain K562/AO_2 as research subject,observing the cell survival and the morphological change of cell apoptosis under the action of ADR and arsenic sulfide and the Caspase-3 activity before and after putting in the Caspase-3 inhibitor.Methods ① The 3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyl-tetrazolium bromide(MTT) method was used to determine the cell survival(A value) of K562/AO_(2)cell strain under the action of ADR and arsenic sulfide.② DNA agarose gel electrophoresis was performed to observe the DNA cleavage of apoptotic cells.③ The enzyme colorimetric activity assay(CAA) method was used to measure the change of the Caspase-3 activity of K562/AO_(2) cell strain.Results ① The A value of K562/AO_(2) cells had a time and dosage dependent relation with arsenic sulfide.② Apoptosis occurred in the K562/AO_(2) cell strain affected by arsenic sulfide.③ Compared with the cell strains with the Caspase-3 inhibitor added,the Caspase-3 activity of those without the Caspase-3 inhibitor increased remarkably(P

The clinical evaluation on chemo-endocrine therapy for advanced gastric carcinoma / 西安交通大学学报(医学版)

Objective To observe the effects of chemo-endocrine therapy on gastric carcinoma (GC). Methods Cancerous tissues from 95 patients with primary GC were examined for the presence of estrogen receptor (ER) and progesterone receptor (PgR). Afterwards, 64 GC patients with recurrent or metastatic conditions were randomly divided into two groups: chemotherapy group and chemo-endocrine therapy group. Results A total of 34.38% ER positive and 16.30% PgR positive rates were found. For ER positive patients, the use of tamoxifen-EAP regimens was more effective than that of EAP alone (P