Yulin Zhu

Non-genetic risk factors and predicting efficacy for docetaxel–drug-induced liver injury among metastatic breast cancer patients

Background and Aim:  Docetaxel has been chosen as one of the most popular anticancer drugs in the treatment of breast cancer for more than a decade. There is increasingly awareness for the occurrence of docetaxel and/or docetaxel–drug‐induced liver injury (DILI), although the underlying mechanism of occurrence and its risk factors remain unclear.

Recombinant human endostatin could eliminate the pro-angiogenesis priority of SP cells sorted from non-small cell lung cancer cells

PurposeTo ascertain the biologic significance of lung cancer Side population (SP) cells, which represent putative cancer stem cells (CSC) in the absence of consensus biomarkers for tumor-specific CSC.Materials and methodsWe sorted and analyzed the angiogenic features of SP cells, isolated from tumor cell lines based on the exclusion of the DNA dye Hoechst 33342, from the NSCLC cell lines A549 and H460.ResultsCompared with non-SP cells, mRNA of vascular endothelial growth factor (VEGF)-A, VEGF-B, angiopoietin (ang)-1, ang-2, fibroblast growth factor-2 (FGF-2), cyclooxygenase-2 (Cox-2) and interleukin-8 (IL-8) were over-expressed in SP cells accompanied by over-expression of ABCG2 and MDR1 mRNA. The supernatant of cultured SP cells could significantly induce migration of human umbilical vein endothelial cells, while recombinant human endostatin (Endostar 25®) could inhibit the migration.ConclusionsThis study revealed that the NSCLC SP cells might represent CSCs and possess pro-angiogenic properties, and antiangiogenesis represent a potential therapy.

Mobilization of peripheral blood stem cells using regimen combining docetaxel with granulocyte colony-stimulating factor in breast cancer patients

ObjectiveTo evaluate the effectiveness and safety of the mobilization of peripheral blood hematopoietic stem cells by combining docetaxel with granulocyte colony-stimulating factor (G-CSF) in breast cancer patients.MethodsA total of 57 breast cancer patients were treated with docetaxel 120 mg/m2. When the white blood cell (WBC) count decreased to 1.0×109/L, patients were given G-CSF 5 μg/kg daily by subcutaneous injection until the end of apheresis. Peripheral blood mononuclear cells (MNC) were isolated by Cobe Spectra Apheresis System. The percentage of CD34+ cell was assayed by flow cytometry.ResultsAt a median 6 of days (range 3–8) after the administration of docetaxel, the median WBC count decreased to 1.08×109/L (range 0.20–2.31). The median duration of G-CSF mobilization was 3 days (range 2–7). The MNC collection was conducted 8–12 days (median 10 days) after docetaxel treatment. The median MNC was 5.35×108/kg (range 0.59–14.07), the median CD34+ cell count was 2.43×106/kg (range 0.16–16.69). The CD34+ cell count was higher than 1.00×106/kg in 47 of 57 cases (82.46%) and higher than 2.00×106/kg in 36 cases (63.16%). The CD34+ cell count was higher than 2.00×106/kg in 27 collections (23.68%). The MNC count and the CD34+ cell count were correlated with the bottom of WBC after docetaxel chemotherapy (r=0.364, 0.502, P=0.005, 0.000). The CD34+ cell count was correlated with the MNC count (r=0.597, P=0.000). The mobilization and apheresis were well tolerated in all patients. Mild perioral numbness and numbness of hand or feet were observed in 3 cases. No serious adverse events were reported.ConclusionMobilization of peripheral blood hematopoietic stem cell by combining docetaxel with G-CSF was effective and safety in breast cancer patients.

Multicenter Clinical Study for Evaluation of Efficacy and Safety of Transdermal Fentanyl Matrix Patch in Treatment of Moderate to Severe Cancer Pain in 474 Chinese Cancer Patients

ObjectiveAlthough a new matrix formulation fentanyl has been used throughout the world for cancer pain management, few data about its efficacy and clinical outcomes associated with its use in Chinese patients have been obtained. This study aimed to assess the efficacy and safety of the new system in Chinese patients with moderate to severe cancer pain.MethodsA total of 474 patients with moderate to severe cancer pain were enrolled in this study and were treated with the new transdermal fentanyl matrix patch (TDF) up to 2 weeks. All the patients were asked to record pain intensity, side effects, quality of life (QOL), adherence and global satisfaction. The initial dose of fentanyl was 25 μg/h titrated with opioid or according to National Comprehensive Cancer Network (NCCN) guidelines. Transdermal fentanyl was changed every three days.ResultsAfter 2 weeks. The mean pain intensity of the 459 evaluated patients decreased significantly from 5.63±1.26 to 2.03±1.46 (P<0.0001). The total remission rate was 91.29%, of which moderate remission rate 53.16%, obvious remission rate 25.49% and complete remission rate 12.64%. The rate of adverse events was 33.75%, 18.78% of which were moderate and 3.80% were severe. The most frequent adverse events were constipation and nausea. No fatal events were observed. The quality of life was remarkably improved after the treatment (P<0.0001).ConclusionThe new TDF is effective and safe in treating patients with moderate to severe cancer pain, and can significantly improve the quality of life.

Abstract 5298: Two distinctive single nucleotide polymorphisms determine liver metastases responses to docetaxel plus thiotepa for metastatic breast cancer patients.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC The successful predictively treatment of metastatic breast cancer (MBC) remains a major challenge. Until now there is no definite marker to distinguish responder from non-responder and more and more important, metastasis occurred within different organs lead to serious variations of overall survival. In this study, paclitaxel and anthracyclines pretreated153 patients with MBC received 606 cycles of docetaxel plus thiotepa. 65 of 153 patients were concurrently diagnosed as MBC involved liver metastasis (LM). Among 153 patients, the response were 1 complete response (CR) (0.7%), 25 partial responses (PR) (16.3%), 73 stable diseases (SD) (47.7%), 46 progressive diseases (PD) (30.1%) and 8 unevaluable(5.2%). For LM patients, the localized liver response were 2 CR (3.1%), 20 PR (30.8%), 16 SD (24.6%), 22 PD (33.8%),5 unevaluable (7.7%). Median PFS and OS for both entire and LM subgroup were 6.5 (95% CI, 5.6 to 7.4) versus 4.2 (95%CI, 2.3-6.1), and 20.0 (95% CI, 15.6 to 24.4) versus 14.2 (95%CI, 9.5-18.9) months respectively. 79 SNPs in CYP450, whose minor allele frequency were ≥ 10% were genotyped. There was no significant difference of SNPs in therapeutic responses, PFS or OS. Of importance, there were two distinctive SNPs, rs2277119 and rs4646487 \*2/\*3 alleles, which tended to have the better liver metastases response than *1 when choosing a false discovery rate as 12%. It seemed that docetaxel plus thiotepa might be regarded as an active specific regimen for MBC with liver metastasis. The generation of conceptually specific chemotherapy targeting the organ with cancer metastasis should be considered in the future. Citation Format: Jing Yu, Ningning Dong, Ying Yan, Bin Shao, Lijun Di, Guohong Song, Li Che, Jun Jia, Hanfang Jiang, Xu Liang, Yulin Zhu, Chaoying Wang, Jie Zahng, Budong Zhu, Xinna Zhou, Xiaoli Wang, Huabing Yang, Jun Ren, Herbert Kim Lyerly. Two distinctive single nucleotide polymorphisms determine liver metastases responses to docetaxel plus thiotepa for metastatic breast cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5298. doi:10.1158/1538-7445.AM2013-5298 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.