TCEA1 regulates the proliferative potential of mouse myeloid cells.

Leukemia is a malignance with complex pathogenesis and poor prognosis. Discovery of noval regulators amenable to leukemia could be of value to gain insight into the pathogenesis, diagnosis and prognosis of leukemia. Here, we conducted a large-scale shRNA library screening for functional regulators in the development of myeloid cells in primary cells. We identified eighteen candidate regulators in the primary screening. Those genes cover a wide range of cellular functions, including gene expression regulation, intracellular signaling transduction, nucleotide excision repair, cell cycle control and transcription regulation. In both primary screening and validation, shRNAs targeting Tcea1, encoding the transcription elongation factor A (SII) 1, exhibited the greatest influence on the proliferative potential of cells. Knocking down the expression of Tcea1 in the 32Dcl3 myeloid cell line led to enhanced proliferation of myeloid cells and blockage of myeloid differentiation induced by G-CSF. In addition, silence of Tcea1 inhibited apoptosis of myeloid cells. Thus, Tcea1 was identified as a gene which can influence the proliferative potential, survival and differentiation of myeloid cells. These findings have implications for how transcriptional elongation influences myeloid cell development and leukemic transformation.

Involvement of CUL4A in regulation of multidrug resistance to P-gp substrate drugs in breast cancer cells.

CUL4A encodes a core component of a cullin-based E3 ubiquitin ligase complex that regulates many critical processes such as cell cycle progression, DNA replication, DNA repair and chromatin remodeling by targeting a variety of proteins for ubiquitination and degradation. In the research described in this report we aimed to clarify whether CUL4A participates in multiple drug resistance (MDR) in breast cancer cells. We first transfected vectors carrying CUL4A and specific shCUL4A into breast cancer cells and corresponding Adr cells respectively. Using reverse transcription polymerase chain reactions and western blots, we found that overexpression of CUL4A in MCF7 and MDA-MB-468 cells up-regulated MDR1/P-gp expression on both the transcription and protein levels, which conferred multidrug resistance to P-gp substrate drugs, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. On the other hand, silencing CUL4A in MCF7/Adr and MDA-MB-468/Adr cells led to the opposite effect. Moreover, ERK1/2 in CUL4A-overexpressing cells was highly activated and after treatment with PD98059, an ERK1/2-specific inhibitor, CUL4A-induced expression of MDR1/P-gp was decreased significantly. Lastly, immunohistochemistry in breast cancer tissues showed that P-gp expression had a positive correlation with the expression of CUL4A and ERK1/2. Thus, these results implied that CUL4A and ERK1/2 participated in multi-drug resistance in breast cancer through regulation of MDR1/P-gp expression.

Adverse reactions and their management in the treatment of malignant tumors using cytokine-induced killer cells.

OBJECTIVE: To identify the causes and the corresponding management of adverse reactions during the treatment of malignant tumors using cytokine-induced killer cells. METHODS: From January 2012 to December 2012, 441 patients received a total of 1,393 autologous cytokine-induced killer cell transfusion cycles in our department. The adverse reactions after the procedures were observed (assessed using the National Cancer Institute Common Toxicity version 2.0), and targeted care and health education were delivered by nurses. RESULTS: All treatment sessions were successfully completed, and the following adverse reactions were found: grade 1/3 fever in 1.36% (19/1,393) patients; grade 2/3 fever in 0.86% (12/1,393) patients; grade 2/3 chills in 0.65% (9/1,393) patients; and grade 1/3 dizziness in 0.29% (4/1,393) patients. CONCLUSIONS: After timely intervention of the adverse reactions, all patients were treated successfully. The best timing of the CIK cell therapy for cancer patients is when the tumor burden, or the number of tumor cells, reaches the minimal level after the end of surgery, chemotherapy and radiation therapy.

[A study of the effect of interstitial (125)I seed implantation on ward nurses' hemogram and relevant protection investigations].

OBJECTIVE: To analyze the blood picture changes of the ward nurses who nurse the patients received (125)I seeds implantation. METHODS: 32 ward nurses who nurse the patients for (125)I seeds implantation were involved in the experimental group, the control group included 32 ward nurses from the medical oncology never exposed to (125)I seeds. The WBC count, hemoglobin concentration and platelet counts from the two groups were analyzed statistically, respectively. 30 patients received (125)I seeds implantation were selected randomly and γ-ray dose from the unshielded group and lead rubber cloth covering group was detected at a distance of 0, 15, 30, 50, 100 cm from patient body surface and at different angles. RESULTS: No significant statistical difference was found between the two groups of WBC count, hemoglobin concentration and platelet count (7.1 ± 1.7 vs 6.8 ± 2.0, 132 ± 11 vs 136 ± 11, 236 ± 57 vs 242 ± 61) . The measured radiation dose was close to the natural background dose (10.2-10.8 µSv/h) at a distance of 50 cm from the body surface [ (12.7 ± 4.3) µSv/h] and the same as after 0.125 mm lead equivalent (Pb) rubber cloth shield protection[ (11.2 ± 3.1) µSv/h]. CONCLUSION: Interstitial (125)I seed implantation is safe on the blood picture of the ward nurses after taking appropriate protective measures.