Aggressive interventions in terminally ill patients with solid tumors in China: a retrospective single center analysis.

PURPOSE: Overtreatment in terminally ill cancer patients is very common worldwide, but whether patients will benefit from aggressive care remains obscure. This study aimed to explore the value of aggressive interventions in the end of life in adult patients with advanced solid tumors. METHODS: All adult patients who died from advanced solid tumors between 2011 and 2012 in Xiangyang Central Hospital were included. Detailed data concerning cancer types, therapy approach and outcome in the last three months of life were collected and assessed. RESULTS: 263 patients with median age 63 years died of cancer between 2011 and 2012. In the last 3 months of life, 82.5% of the patients received aggressive care, especially chemotherapy and radiotherapy. Traditional Chinese medicine was widely used. Median survival from diagnosis of metastasis to death was 6.9 months for patients treated with aggressive care and 6.2 months for the others, respectively (p>0.05). CONCLUSION: Despite their wide use, aggressive interventions in the last 3 months of life might have no benefit on survival. Radiotherapy provided significant symptom palliation of bone or brain metastases, but the short-course radiotherapy schedule was rarely used. Frequent reassessment of patients and making decision together with the patients is helpful to overcome the aggressive care. Appropriate tools to predict survival are needed to help design proper strategies for terminally ill cancer patients.

Lipopolysaccharide initiates a bypass feedback loop of epidermal growth factor receptor signaling by HPS70-induced COX-2 in H22 hepatocarcinoma cells.

LPS can induce TACE upregulation via signaling from TLR4-derived EGFR activation in tumor cells. The regulation and activity of TACE have been investigated with the observation that gene expression is upregulated in response to LPS followed by EGFR activation, however, the process remains poorly understood. In this study, we examined the effects of LPS on H22 hepatocarcinoma cells that displayed constitutively active TLR4 expression. Upon TLR4 shRNA transfection into H22 cells, HSP70 expression significantly increased. However, LPS induced early phosphorylation of EGFR in H22 cells, which reached maximum levels within 30 min. Inhibition of TLR4 in H22 cells resulted in a significant rise in both EGFR phosphorylation and TACE upregulation 24 h after exposure to LPS. Exogenous HSP70 also induced rapid phosphorylation of EGFR, upregulated the expression of COX-2 via a signaling pathway that involved TACE-dependent TGF-α release. Furthermore, inhibition of EGFR activation and reduction of COX-2 expression by COX-2 inhibitor prevented HSP70-induced cell invasion in vitro. These findings demonstrate that the biological importance of HSP70/COX-2 is crucial to the second, but not the first, phase of EGFR phosphorylation in tumor cells. The growth of tumor cells by inserting shRNA plasmid TLR4 combination with COX-2 inhibitor could be effectively reduced in LPS stimulation. We concluded that LPS triggered a bypass feedback loop of EGFR activation and involved HSP70/COX-2 in H22 cells by inhibition of TLR4 and that EGFR phosphorylation is implicated in tumor growth by LPS stimulation.

The relationship among human papilloma virus infection, survivin, and p53 gene in lung squamous carcinoma tissue.

OBJECTIVE: To study the relationship between the infection of human papillomavirus (HPV) type 16, type 18, the expression of survivin, and the mutation of p53 gene in lung squamous carcinoma tissue for the research of pathogenesis of lung carcinoma. METHODS: This study was carried out at the Laboratory of Molecular Biology, Xiangfan Central Hospital of Hubei Province, China from September 2008 to May 2010. Forty-five specimens of lung squamous carcinoma tissue confirmed by histopathology were the excisional specimens taken by the Thoracic Surgery of Xiangfan Central Hospital. Normal tissue, closely adjacent to the fresh carcinoma specimens, was used as the control group for p53 gene mutation analysis. Sixteen surgical excisional specimens of benign lung disease were used as a control group of non-carcinomatous diseases. Human papillomavirus DNA were detected by polymerase chain reaction (PCR), and we used the PCR-single-strand conformation polymorphism-ethidium bromide (PCR-SSCP-EB) method to detect the mutations of the p53 gene. The expression of the survivin gene was detected by immunohistochemistry methods. RESULTS: Approximately 68.9% of 45 lung squamous carcinoma tissue had p53 gene mutations. The mutation rate of exon 5-8 p53 were 15.6%, 17.8%, 15.6% and 20%. Approximately 42.2% of lung squamous cell carcinoma samples were shown to be positive for HPV DNA expression and 62.2% were positive for survivin expression. There was an inverse correlation between the presence of HPV infections and mutations of p53 gene; and the mutations of p53 gene and expression of survivin had a positive relationship. CONCLUSION: Mutation of p53 gene and HPV infection may facilitate each other in the generation of lung squamous cell carcinoma. Abnormal expression of the survivin gene may take part in the onset and progression of lung squamous cell carcinoma.