KIF22 promotes progress of esophageal squamous cell carcinoma cells and is negatively regulated by miR-122.

Esophageal squamous cell carcinoma (ESCC) increases at fast rate of all cancer types in China, which urges the investigations of its potential mechanism. In this research, a highly expressed kinesin superfamily protein 22 (KIF22) was founded both in ESCC tissues and cancer cell lines. The following experiments pointed out that down-regulation of KIF22 remarkably restrained the malignant progression of ESCC cells. Besides, KIF22 knockdown promoted ESCC cells apoptosis and arrested cells in G0/G1 phase, while KIF22 also regulated the expression of cell cycle- and EMT-related proteins. Previous research revealed that the aberrant expressions of microRNAs (miRNAs) are related to tumors development. Based on the predict result, KIF22 was considered as the target of miR-122, which was demonstrated by luciferase reporter assay. miR-122 inhibitor could significantly reverse the function of KIF22 knockdown, including cell proliferation, migration and invasion. Furthermore, down-expressed miR-122 altered the function of KIF22 knockdown on cell cycle- and EMT-related proteins. In a word, this work illustrated the regulatory function of KIF22/miR-122 axis in ESSC and provided potential targets for potential targets for ESSC treatment.

Pathological response and serum VEGF changes during chemoradiotherapy for esophageal carcinoma.

The aim of this study was to observe pathological response and change in serum vascular endothelial growth factor (VEGF) in esophageal carcinoma (EC) during chemoradiotherapy (CRT).Eighty-nine patients diagnosed with EC were treated with radiotherapy at the Department of Radiotherapy of the Second People's Hospital of Changzhou between May 2008 and December 2014, including 65 patients with CRT. Gastroscopy and pathological examination were conducted 4 weeks afterwards. The pathological responses were classified as complete response (CR) and non-CR. Serum samples were collected from the patients before radiotherapy, during week 4 of radiotherapy, and 1 week after radiotherapy. The VEGF changes were classified as increase, stable, and decrease.The median overall survival (OS) and median progression-free survival (PFS) in the pathological CR group was significantly longer than that of the non-CR group (P < .001). The 1-, 3-, and 5-year OS rates in the non-CR group were lower than that in the CR group (P < .05). Moreover, the 1-, 3-, and 5-year PFS rates in the non-CR group were lower than that in the CR group (P < .05). VEGF serum level was decreased during and after radiotherapy compared with pre-radiotherapy, and the differences were statistically significant (P < .05). The 1-, 3-, and 5-year OS rates in the increased group were lower than that in the decreasing group (P < .05). Moreover, the 1-, 3-, and 5-year PFS rates in the increasing group were lower than that in the decreasing group (P < .05). Pathological response (P < .05), serum VEGF trend (P < .05), and tumor-node-metastasis stage (P < .05) in response to CRT were factors that influenced patient prognosis.Pathological response and serum VEGF change during CRT can predict prognosis of nonsurgical patients with EC. Monitoring these changes is of significance in individualized treatment.

Pathologic response during chemo-radiotherapy and variation of serum VEGF levels could predict effects of chemo-radiotherapy in patients with esophageal cancer.

BACKGROUND: To investigate the relationship between pathologic tumor response to concurrent chemo- radiotherapy and variation of serum VEGF in patients with esophageal cancer. MATERIALS AND METHODS: Forty six patients with esophageal cancer who were treated with concurrent chemo-radiotherapy were enrolled. Endoscopic and pathologic examination was conducted before and four weeks afterwards. Serum level of VEGF was documented before, four weeks later and after chemo-radiotherapy. The relationship between pathologic response and the variation of serum level of VEGF and its influence on the prognosis were investigated. RESULTS: Serum level of VEGF decreased remarkably during and after chemo-radiotherapy in patients whose pathologic response was severe (F=5.393, 4.587, P(0.05). There were no statistical differences of serum VEGF level before, during and after chemo-radiotherapy for patients whose pathologic response was moderate or mild. There were 18 (85.7%), 7 (53.8%) and 6 patients (50.0%) whose serum VEGF level dropped in the severe, moderate and mild group, respectively, with significant differences among these groups (p=0.046). Two year survival rates of patients with severe, moderate and mild pathologic response were 61.9%, 53.8% and 33.3% respectively, and no statistically difference between severe and mild group regarding OS (p=0.245) was tested. CONCLUSIONS: Tumor pathologic response during chemo-radiotherapy and the changes of serum VEGF lever could predict curative effects of chemo-radiotherapy in patients with esophageal cancer.

Clinical trial of thalidomide combined with radiotherapy in patients with esophageal cancer.

AIM: To investigate the short-term efficacy and tolerability of radiotherapy plus thalidomide in patients with esophageal cancer (EC). METHODS: Serum samples from 86 EC patients were collected before, during, and after radiotherapy, and the vascular endothelial growth factor (VEGF) level was examined by ELISA. According to the change in serum VEGF level during radiotherapy, the patients were divided into two groups: in the drug group, VEGF level was increased or remained unchanged, and thalidomide was administered up to the end of radiotherapy; in the non-drug group, VEGF level was decreased and radiotherapy was given alone. Thirty healthy volunteers served as controls. The efficacy and safety of radiotherapy plus thalidomide therapy were investigated. RESULTS: The 86 EC patients had a significantly higher level of VEGF compared with the 30 healthy controls before radiotherapy (P < 0.01), and the VEGF level was significantly correlated with primary tumor size, lymph node metastasis, histopathologic type, and clinical stage (P < 0.01). Of 83 evaluable cases, VEGF level was significantly decreased after radiotherapy in 32 patients in the drug group (P < 0.05), with an effective rate of 71.88%. The incidence of dizziness and/or burnout in the drug group and non-drug group was 62.50% and 15.69%, respectively (P = 0.000), and the incidence of somnolence was 12.50% and 0%, respectively (P = 0.019). No significant differences were observed. CONCLUSION: Thalidomide can down-regulate serum VEGF level in EC patients, and combined with radiotherapy may improve treatment outcome. Thalidomide was well tolerated by EC patients.

Radiobiological characteristics of cancer stem cells from esophageal cancer cell lines.

AIM: To study the cancer stem cell population in esophageal cancer cell lines KYSE-150 and TE-1 and identify whether the resulting stem-like spheroid cells display cancer stem cells and radiation resistance characteristics. METHODS: A serum-free medium (SFM) suspension was used to culture esophageal cancer stem cell lines and enrich the esophageal stem-like spheres. A reverse transcription polymerase chain reaction assay was used to detect stem cell gene expression in the spheroid cells. Radiosensitivity of stem-like spheres and parental cells were evaluated by clonogenic assays. Furthermore, different cells after different doses of irradiation were tested to evaluate the change in sphere formation, cell cycle and CD44(+)CD271(+) expression of tumor stem-like spheroid cells using flow cytometry before and after irradiation. RESULTS: The cells were observed to generate an increased number of spheres in SFM with increasing cell passage. Radiation increased the rate of generation of stem-like spheres in both types of cells. The average survival fraction (SF2) of the cultured KYSE-150 compared with TE-1 stem-like spheres after 2 Gy of radiation was 0.81 ± 0.03 vs 0.87 ± 0.01 (P < 0.05), while the average SF2 of KYSE-150 compared with TE-1 parental cells was 0.69 ± 0.04 vs 0.80 ± 0.03, P < 0.05. In the esophageal parental cells, irradiation dose-dependently induced G2 arrest. Stem-like esophageal spheres were resistant to irradiation-induced G2 arrest without significant changes in the percentage population of irradiated stem-like cells. Under irradiation at 0, 4, and 8 Gy, the CD44(+)CD271(+) cell percentage for KYSE150 parental cells was 1.08% ± 0.03% vs 1.29% ± 0.07% vs 1.11% ± 0.09%, respectively; the CD44(+)CD271(+) cell percentage for TE1 parental cells was 1.16% ± 0.11% vs 0.97% ± 0.08% vs 1.45% ± 0.35%, respectively. The differences were not statistically significant. Under irradiation at 0, 4, and 8 Gy, the CD44(+)CD271(+) cell percentage for KYSE-150 stem-like spheres was 35.83% ± 1.23% vs 44.9% ± 1.67% vs 57.77% ± 1.88%, respectively; the CD44(+)CD271(+) cell percentage for TE1 stem-like spheres was 16.07% ± 0.91% vs 22.67% ± 1.12%, 16.07% ± 0.91% vs 33.27% ± 1.07%, respectively. The 4 and 8 Gy irradiated KYSE-150 and TE-1 stem-like spheres were compared with the 0 Gy irradiated group, and the differences were statistically significant (P < 0.05). CONCLUSION: The KYSE-150 and TE-1 stem-like spheres are more radioresistant than their parental cells which may suggest that cancer stem cells are related to radioresistance.

Genomewide association study of leprosy.

BACKGROUND: The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression. METHODS: We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary). RESULTS: We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy. CONCLUSIONS: Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae.

[Analysis of serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in benign prostatic hyperplasia].

OBJECTIVES: To determine changes of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) in serum samples from benign prostatic hyperplasia (BPH) patients and to evaluate the value of these molecules as possible etiologic factors for BPH. METHODS: The serum IGF-1 and IGFBP-3 levels were measured with immunoradiometric assay(IRMA) in 64 cases of BPH and in 30 healthy subjects as controls. The cases of BPH were divided into 3 groups according to the prostate volume(PV). There were 18 cases(PV < or = 30 ml) in group A, 24 cases(PV31 approximately 50 ml) in group B, 22 cases(PV > or = 50 ml) in group C. RESULTS: There were no statistical differences between the levels of Both IGF-1 and IGFBP-3 in BPH groups and healthy groups (both P > 0.05), but there were statistical differences among three groups of BPH. Both IGF-1 and IGFBP-3 levels in group C of BPH were significantly higher than those in group A (both P < 0.05). A positive correlation between the serum levels of IGF-1 and PV displayed(r = 0.58), as well as IGFBP-3 (r = 0.48). CONCLUSIONS: Together these observations implicate IGF-1 and IGFBP-3 as important factors during the progression of BPH. It shows the value of non-operation treatment for this disease.