A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFα-TGFα-EGFR.

Peritoneum is the most common site for ovarian cancer metastasis. Here we investigate how cancer epigenetics regulates reciprocal tumor-stromal interactions in peritoneal metastasis of ovarian cancer. Firstly, we find that omental stromal fibroblasts enhance colony formation of metastatic ovarian cancer cells, and de novo expression of transforming growth factor-alpha (TGF-α) is induced in stromal fibroblasts co-cultured with ovarian cancer cells. We also observed an over-expression of tumor necrosis factor-alpha (TNF-α) in ovarian cancer cells, which is regulated by promoter DNA hypomethylation as well as chromatin remodeling. Interestingly, this ovarian cancer-derived TNF-α induces TGF-α transcription in stromal fibroblasts through nuclear factor-κB (NF-κB). We further show that TGF-α secreted by stromal fibroblasts in turn promotes peritoneal metastasis of ovarian cancer through epidermal growth factor receptor (EGFR) signaling. Finally, we identify a TNFα-TGFα-EGFR interacting loop between tumor and stromal compartments of human omental metastases. Our results therefore demonstrate cancer epigenetics induces a loop of cancer-stroma-cancer interaction in omental microenvironment that promotes peritoneal metastasis of ovarian cancer cells via TNFα-TGFα-EGFR.

FGF8b oncogene mediates proliferation and invasion of Epstein-Barr virus-associated nasopharyngeal carcinoma cells: implication for viral-mediated FGF8b upregulation.

The fibroblast growth factor 8b (FGF8b) oncogene is known to be primarily involved in the tumorigenesis and progression of hormone-related cancers. Its role in other epithelial cancers has not been investigated, except for esophageal cancer, in which FGF8b overexpression was mainly found in tumor biopsies of male patients. These observations were consistent with previous findings in these cancer types that the male sex-hormone androgen is responsible for FGF8b expression. Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer of head and neck commonly found in Asia. It is etiologically associated with Epstein-Barr Virus (EBV) infection, inflammatory tumor microenvironment and relatively higher male predominance. Here, we reported for the first time that FGF8b is overexpressed in this EBV-associated non-hormone-related cancer of the head and neck, NPC. More importantly, overexpression of FGF8b mRNA and protein was detected in a large majority of NPC tumors from both male and female genders, in addition to multiple NPC cell lines. We hypothesized that FGF8b overexpression may contribute to NPC tumorigenesis. Using EBV-associated NPC cell lines, we demonstrated that specific knockdown of FGF8b by small interfering RNA inhibited cell proliferation, migration and invasion, whereas exogenous FGF8b stimulated these multiple phenotypes. Further mechanistic investigation revealed that in addition to NF-κB signaling (a major inflammatory signaling pathway known to be activated in NPC), an important EBV oncoprotein, the latent membrane protein 1 (LMP1), was found to be a direct inducer of FGF8b overexpression in NPC cells, whereas androgen (testosterone) has minimal effect on FGF8b expression in EBV-associated NPC cells. In summary, our study has identified LMP1 as the first viral oncogene capable of directly inducing FGF8b (an important cellular oncogene) expression in human cancer cells. This novel mechanism of viral-mediated FGF8 upregulation may implicate a new role of oncoviruses in human carcinogenesis.

Removal of batteries from solid waste using trommel separation.

This paper describes the design and testing of a trommel for separation of batteries from solid waste. A trommel is a cylindrical separation device that rotates and performs size separation. It has also been used in areas such as municipal solid waste (MSW) processing, classifying construction and demolition debris, screening mass-burn incinerator ash and compost processing. A trommel has been designed based on size separation to separate household batteries from solid waste, which can then be used as feedstock for alternative applications of solid waste combustion, particularly where the metal content of the product is also a critical parameter, such as the Co-Co process for integrated cement and power production. This trommel has been tested with batches of university office and restaurant wastes against various factors. The recovery efficiency of batteries increases with decreasing inclination angle of the trommel and decreasing rotational speed. A physical characterization of the university solid waste has been performed with a 20-kg sample of the tested waste. It was found that there is a trend of decreasing recovery of batteries with increasing paper composition, and a trend of increasing recovery of batteries with increasing organic materials composition.

Total flavones of Hippophae rhamnoides promotes early restoration of ultimate stress of healing patellar tendon in a rat model.

Traditional Chinese herbal medicine has long been used for treatment of tendon injuries. Comparing to the modern way of treatments, Traditional Chinese medicine also stresses on strategies to promote the inherent healing capacity of tendons. Hippophae rhamnoides, known as Shaji, is one of Chinese herbal drugs that are traditionally used to promote tendon and ligament injuries. The total flavones of H. rhamnoides (TFH), with major constituents including quercetin, isorhamnetin and kaempferol, have been demonstrated with most of the bioactive properties of Shaji. In the present study, we evaluated the potential effect of TFH in the restoration of ultimate stress of healing patellar tendon in a well-established gap wound model in rats. A 0.1 mg TFH was injected to wound 1 day after the injury, and the ultimate stress of the healing tendon was measured at day 14 post-injury. The results showed that the ultimate stress of the healing tendon was significantly promoted by injection of TFH, increasing from 30 to 50% as compared to saline control. Excessive fibrotic response was not found in TFH-treated animals, but an enhanced collagen deposition and a better fibre alignment were observed. The results suggest that TFH may improve the ultimate stress of healing tendons at early stages, which implies possible earlier rehabilitation programme and better recovery.

Film-pore diffusion modeling for the sorption of metal ions from aqueous effluents onto peat.

The sorption of three metal ions, namely, copper, nickel and lead onto sphagnum peat moss has been studied using an agitated batch sorber system. The equilibrium isotherms were determined and kinetic runs were performed over a range of concentrations for each metal ion. A film-pore diffusion mass transfer model has been developed based on a single effective diffusion coefficient for each system. Error analysis of the experimental and theoretical data indicated relatively large errors at low initial metal ion concentrations. Therefore the model was modified to introduce a surface coverage concentration dependent effective diffusivity to account for a contribution from surface diffusion.

Macrophage migration inhibitory factor is an important mediator in the pathogenesis of gastric inflammation in rats.

BACKGROUND & AIMS: Macrophage migration inhibitory factor (MIF) has been shown to play a pivotal role in inflammatory and immune-mediated diseases. This study investigates the role of MIF in gastric inflammation. METHODS: Expression of MIF was examined in a rat gastric ulcer model induced by acetic acid, and the functional role of MIF in acute gastric ulcer was investigated by administration of a neutralizing anti-MIF antibody. RESULTS: MIF messenger RNA and protein were markedly up-regulated in acute gastric ulcer, which correlated with the accumulation of macrophages (P < 0.001) and neutrophils (P < 0.05) at the site of inflammation. Macrophages, like neutrophils, were the major inflammatory cells infiltrating the ulcer base and they strongly expressed inducible nitric oxide synthase. However, macrophages, not neutrophils, were a rich source of MIF production in acute gastric ulcer. In vivo and in vitro blockade of MIF with the neutralizing anti-MIF antibody significantly inhibited the marked up-regulation of MIF, tumor necrosis factor alpha, inducible nitric oxide synthase, and intercellular adhesion molecule-1. This was associated with the marked inhibition of macrophage (70% reduced) and neutrophil (60% reduced) accumulation and activation, thus reducing ulcer sizes and attenuating ulceration. CONCLUSIONS: This study has shown that MIF was markedly up-regulated during acute gastric ulcer. Inhibition of acute gastric ulcer by blockade of MIF indicates that MIF is a key inflammatory mediator and plays a pathogenic role in gastric inflammation.

Neonatal jaundice: its prevalence in Chinese babies and associating factors.

A prospective study of 1238 full-term Chinese newborn infants was conducted to determine the incidence of neonatal jaundice and associated factors. A significantly more severe degree of hyperbilirubinaemia was present in infants whose ABO blood group was incompatible with that of their mothers and those who were deficient in the enzyme glucose-6-phosphate dehydrogenase (G6PD). Among the remainder, clinical jaundice was present in 87% and 23.9% had a peak serum bilirubin (SB) concentration greater than 204 mumol/l. Factors that were found to have an association with a higher peak SB concentration included: male infants; elder siblings who had a history of neonatal jaundice; and breast-fed infants with or without supplementation with formula feed. Factors that were found to have no significant association with the peak SB concentration were: gestational age; birthweight; the mode of delivery of the infants; maternal consumption of Chinese herbs and syntocinon induction or augmentation of labour.

Transcutaneous bilirubinometer: its use in Chinese term infants and the effect of haematocrit and phototherapy on the TcB index.

The application of the transcutaneous bilirubinometer in screening for neonatal jaundice was evaluated in 259 full-term Chinese infants: 202 who had not received any treatment and 57 who were receiving phototherapy. The transcutaneous bilirubin index correlated well with the serum bilirubin level (SB) of the untreated infants and the coefficient of correlation was slightly higher for TcB readings obtained over the mid-sternal area (r = 0.91; P less than 0.001) than those over the forehead (r = 0.85; P less than 0.001). Transcutaneous bilirubinometry was unreliable in predicting the SB level in infants receiving phototherapy even if the SB readings were obtained over shaded skin. The haematocrit of the infants, though having a statistically significant effect on the TcB index, contributed only minimally to the regression line and correlation coefficient between the TcB index and SB level.