To study the influence of the number of metastatic lymph nodes (LNs) on survival and International Union Against Cancer tumor-node-metastasis (TNM) classification for esophageal carcinoma. The clinicopathological data on 1146 patients with esophageal squamous cell carcinoma who had undergone an esophagectomy were retrospectively studied. Survival was analyzed by the Kaplan-Meier method. By subclassifying the nodes (N) category according to the number of metastatic LNs as: N0 for no LN metastases; N1(1) for only one positive node; and N1(2) for >or=2 positive nodes. TNM staging was refined as stage IIa (T2-3N0M0), stage IIb (T1N1M0 and T2N1(1)M0), stage IIIa (T2N1(2)M0 and T3N1(1)M0), and stage IIIb (T3N1(2)M0 and T4NanyM0), and the survival was analyzed. LN metastases was found in 380 of 1146 (33.2%) treated esophageal cancer patients. In 4270 LNs harvested, metastases was detected in 807 (18.9%). The 5-year survival rates of the patients with 0, 1, and >or=2 positive nodes were 59.8, 33.4, and 9.4%, respectively. There was statistically significant difference among these three groups. The 5-year survival of the patients in stages T2N1M0 and T3N1M0 was significantly higher in the N1(1) group than in the N1(2) group (41.5 vs 24.1%, and 31.2 vs 6.8%, P<0.001). The 5-year survival rates of the patients in refined stage IIa, IIb, IIIa, and IIIb were 57.1, 42.2, 28.6, and 8.5%, with significant difference existing in each stage groups. The number of positive LNs significantly influenced survival of the patients with esophageal cancer. Three grade classification (0, 1, >or=2 positive nodes) could quite well demonstrate the effect of the number of LN metastases and the survival. The refined TNM classification based on the number of LN metastases could better reflect the prognosis of esophageal cancer. Our results offer a strong rationale for refining the International Union Against Cancer TNM classification for esophageal carcinoma.

Porcine epidemic diarrhea (PED) caused by virulent strains of porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric disease of swine characterized by severe enteritis, vomiting, and watery diarrhea. This study investigates the subcellular localization and function of PEDV M protein through examination of its effects on cell growth, cell cycle progression, and interleukin 8 (IL-8) expression. Our results revealed that the PEDV M protein is localized throughout the cytoplasm. The M protein altered swine intestinal epithelial cell line (IEC) growth and induced cell cycle arrest at the S-phase via the cyclin A pathway. The S-phase arrest is associated with a decrease in level of cyclin A. Furthermore, our results revealed that the M protein of PEDV does not induce endoplasmic reticulum (ER) stress and does not activate NF-κB which is responsible for IL-8 and Bcl-2 expression. This is the first report to demonstrate that the PEDV M protein is localized in the whole cell and induces cell cycle arrest at the S-phase. This study provides novel findings in the function of M proteins of PEDV.

The tumor suppressor p53 has an important role in inducing cell-intrinsic responses to DNA damage, including cellular senescence or apoptosis, which act to thwart tumor development. It has been shown, however, that senescent or dying cells are capable of eliciting inflammatory responses, which can have pro-tumorigenic effects. Whether DNA damage-induced p53 activity can contribute to senescence- or apoptosis-associated pro-tumorigenic inflammation is unknown. Recently, we generated a p53 knock-out rat via homologous recombination in rat embryonic stem cells. Here we show that in a rat model of inflammation-associated hepatocarcinogenesis, heterozygous deficiency of p53 resulted in attenuated inflammatory responses and ameliorated hepatic cirrhosis and tumorigenesis. Chronic administration of hepatocarcinogenic compound, diethylnitrosamine, led to persistent DNA damage and sustained induction of p53 protein in the wild-type livers, and much less induction in p53 heterozygous livers. Sustained p53 activation subsequent to DNA damage was accompanied by apoptotic rather than senescent hepatic injury, which gave rise to the hepatic inflammatory responses. In contrast, the non-hepatocarcinogenic agent, carbon tetrachloride, failed to induce p53, and caused a similar degree of chronic hepatic inflammation and cirrhosis in wild type and p53 heterozygous rats. These results suggest that although p53 is usually regarded as a tumor suppressor, its constant activation can promote pro-tumorigenic inflammation, especially in livers exposed to agents that inflict lasting mutagenic DNA damage.

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