Clinicopathological characteristics and health care for Tibetan women with breast cancer: a cross-sectional survey.

BACKGROUND: The healthcare system (HCS) improved in Tibet Autonomous Region (TAR), China. The present study aimed to investigate whether these improvements might alter the clinicopathological characteristics of a Tibetan female with breast cancer (BC) in TAR. METHODS: This was a single-center cross-sectional study conducted at TAR People's Hospital. All Tibetan adult women were treated for BC in this hospital between January 1, 1973 and December 31, 2015. The inclusion criteria were as follows: (1) Tibetan adult woman living in Tibet; (2) Histopathology or cytopathology or both confirming primary BC; (3) All the treatments were finished in this hospital. χ2 test and logistic regression were applied, using age group and census register as the two covariates. RESULTS: A total of 273 patients with BC were included in the final analysis. Of these, 14 patients were in the free HCS, 183 patients had medical insurance combined with a new rural cooperative HCS, and 76 were in a rural and urban integration HCS. Currently, a rural and urban integration HCS is an improved system. Consequently, an increase in the proportion patients in the T1-3 stage was observed (0.198; 0.046 to 0.852) between the rural and urban integration HCS and free HCS. The proportion of patients in early (I + II) stage cancer (0.110; 0.019-0.633) also increased between these two HCSs. CONCLUSION: This was the first report about Tibetan women with BC in Tibet. Some clinicopathological characteristics at the presentation of Tibetan women with BC may improve during different HCSs. The cancer awareness, early detection, and the overall management in patients with advanced stage BC might improve the prognosis of BC in the rural and urban integration HCS.

CD14 overexpression upregulates TNF-α-mediated inflammatory responses and suppresses the malignancy of gastric carcinoma cells.

CD14 mediates the inflammatory response via recognition of lipopolysaccharide, which has been implicated in Helicobacter pylori (H. pylori) infections. Increasing evidence has suggested that CD14 status significantly influences the clinical outcome of H. pylori infection, which can result in gastric carcinoma. However, there is little evidence regarding the cellular impact and associated molecular basis of CD14 on gastric carcinoma cells. To address this question, we generated a CD14-overexpressing SGC-7901 gastric carcinoma cell line and analyzed the impact of CD14 expression. Our results revealed that cells overexpressing CD14 exhibited antitumor potential, including significantly decreased clonogenic ability, proliferation, metastatic invasion, as well as enhanced apoptosis, suggesting a tumor-suppressive role of CD14 in the cells. Intriguingly, we further discovered that CD14 overexpression activated NF-κB via upregulating its expression and simultaneously stimulating DNA binding activity. Upregulated NF-κB transcriptionally elevated a series of pro-inflammatory cytokines, including TNF-α, IL-1ß, IL-6, and IL-12. Together, the current study utilized a CD14-overexpressing gastric cell model to determine the impacts of CD14 upregulation on cell viability, apoptosis, and migration and NF-κB-mediated inflammation.

CD14 knockdown reduces lipopolysaccharide-induced cell viability and expression of inflammation-associated genes in gastric cancer cells in vitro and in nude mouse xenografts.

The present study examined the role of CD14 in the regulation of lipopolysaccharide (LPS)-induced effects on gastric cancer cells. MGC­803 cells were stably transfected with CD14 short hairpin (sh)RNA and treated with LPS, followed by assessment of cell proliferation, apoptosis and gene expression using a cell counting kit­8 assay, flow cytometry, reverse transcription­polymerase chain reaction and western blot analysis, respectively. The cells subjected to CD14 knockdown were treated with 10 g/ml LPS and injected into nude mice to form tumor xenografts. CD14 shRNA­transfected MGC­803 cells did not exhibit any significant changes in cell viability compared with the control cells (P>0.05), but cell viability was markedly increased in the wild­type (WT) + LPS group (P<0.05). In contrast to the WT + LPS group, the cell viability of the sh­CD14 + LPS group was markedly decreased (P<0.05). In addition, compared with those in the controls, the level of sh­CD14 cell apoptosis did not change significantly; however, it was markedly reduced in the LPS group. Compared with that in the WT + LPS group, the rate of apoptosis in the sh­CD14 + LPS group increased to a certain extent, while it remained lower in the control group. In addition, compared with that in the control, the expression of tumor necrosis factor­α, interleukin (IL)­1, IL­6 and IL­12, and human ß­defensin 2 was significantly increased in the WT + LPS group, while, compared with that in the WT + LPS group, the expression of these genes was markedly reduced in the sh­CD14 + LPS group (P<0.05). The nude mouse experiments further confirmed the in vitro data, including the finding that LPS promoted the growth of xenografts, but knockdown of CD14 expression reduced the response of tumor cells to LPS treatment. In conclusion, LPS induced cell viability and the release of inflammatory cytokines, but inhibited gastric cancer cell apoptosis. Knockdown of CD14 expression had no significant effect on gastric cancer malignancy, but mediated LPS signal transduction.

Association of CD14/-260 polymorphism with gastric cancer risk in Highland Tibetans.

AIM: To investigate the relationship between CD14-260 and -651 polymorphisms and the risk of developing gastric cancer. METHODS: DNA was extracted from peripheral blood samples obtained from 225 Tibetans with gastric cancer and 237 healthy Tibetans, and analyzed using the polymerase chain reaction/ligase detection (PCR/LDR) method to determine the genotypes at -260 and -651 loci of the CD14 promoter. The allele frequencies, genotype frequencies, and haplotypes were analyzed for their association with gastric cancer risk using online SHEsis software. The luciferase reporter assay and point mutation analysis were used to construct in vitro plasmids expressing a C/T homozygote at the -260 locus of the CD14 promoter. RESULTS: The frequencies of CC, CT and TT genotypes in the CD14-260 C/T locus in gastric cancer patients were 19.1%, 38.7% and 42.2%, respectively, whereas they were 33.3%, 32.5% and 34.2%, respectively, in healthy control subjects. CT genotype carriers were more frequently found among gastric cancer patients than healthy controls (OR = 2.076; 95%CI: 1.282-3.360). Also, TT genotype carriers were more frequently found among gastric cancer patients (OR = 2.155; 95%CI: 1.340-3.466). Compared to the C allele of CD14/-260, the T allele was associated with an increased risk for gastric cancer (OR = 1.574; 95%CI: 1.121-2.045). Furthermore, the frequencies of CC, CT and TT in the CD14-651 C/T locus in gastric cancer patients were 64.4%, 29.3% and 6.2%, respectively, while they were 56.5%, 35.0% and 8.4%, respectively, in the healthy control subjects (P > 0.05). Data obtained using the luciferase reporter assay showed that the p260T homozygote was associated with greater CD14 promoter activity (P < 0.01). CONCLUSION: CD14/-260 polymorphism is associated with gastric cancer risk in Highland Tibetans and affects CD14 promoter activity, thereby regulating CD14 expression.

CD14 regulates gastric cancer cell epithelial­mesenchymal transition and invasion in vitro.

Cluster of differentiation 14 (CD14) protein functions as a co-receptor with either the Toll-like receptor TLR4 or MD-2 in the detection of bacterial lipopolysaccharide (LPS) and plays a role in the innate immune system. Recently, it was shown to have effects on the regulation of epithelial-mesenchymal transition (EMT). Thus, the present study investigated the effects of CD14 knockdown on the regulation of gastric cancer cell EMT and invasive capacity following treatment with or without LPS. Knockdown of CD14 expression using CD14 shRNA in MGC-803 cells significantly enhanced E-cadherin expression, but reduced N-cadherin and vimentin expression in both LPS-treated and untreated cells. Morphologically, the phenotype of LPS-treated CD14-knockdown cells was altered to a sporadic long spindle shape. Moreover, TNF-α-treated cells were further elongated, connections between cells were reduced, the gap between the cells was increased and the cells were transformed into mesenchymal cells. Furthermore, the invasive capacity of CD14-knockdown cells was significantly lower compared to that of the negative control shRNA-transfected MGC-803 cells. LPS-treated CD14-knockdown cells had significantly lower levels of tumor cell invasive ability when compared to the LPS-treated parental MGC-803 cells. However, addition of TNF-α to LPS-treated CD14-knockdown cells significantly increased tumor cell invasion. This study demonstrated that CD14 promoted tumor cell EMT and invasion through TNF-α, whereas knockdown of CD14 expression inhibited gastric cancer cell invasion and EMT.