Microbial community reshaped in gastric cancer.

Patients with gastric cancer harbor distinct microbiota in the stomach. It features with lowered biodiversity, discrete structure, and varied composition. Some bacteria from gastric microbiota are potentially carcinogenic as they are enriched or depleted in gastric cancer. Distinct profile of microbial community in gastric cancer is possibly resulted from altered caused by pathophysiological and environmental factors. H. pylori is a carcinogen colonizing the human stomach. Although persisting for decades, it rarely causes compositional alteration of microbiota. Secretion of acid decreases gradually during the carcinogenic process. Increased pH results in overgrowth of bacteria in gastric fluid. The abundance of a particular taxon, but not the profile of microbiota, is altered in proton pump inhibitor users. Compositions of microbiota vary substantially between individuals, which may account for differential cancer risk. It has been demonstrated that genetic variations contribute to inter-individual variations in gut microbiota. However, their influence on the composition of gastric microbiota requires further exploration. Currently, it appears disrupted homeostasis and inter-individual variations of gastric microbiota are involved in cancer development. Clarifying factors responsible for these changes would reveal how microbiota induces carcinogenesis, benefiting the prevention of gastric cancer.

LKB1 inhibits HPV-associated cancer progression by targeting cellular metabolism.

Liver kinase B1 (LKB1) is mutationally inactivated in Peutz-Jeghers syndrome and in a variety of cancers including human papillomavirus (HPV)-caused cervical cancer. However, the significance of LKB1 mutations in cervical cancer initiation and progress has not been examined. Herein, we demonstrated that, in mouse embryonic fibroblasts, loss of LKB1 and transduction of HPV16 E6/E7 had an additive effect on constraining cell senescence while promoting cell proliferation and increasing glucose consumption, lactate production and ATP generation. Knockdown of LKB1 increased and ectopic expression of LKB1 decreased glycolysis, anchorage-independent cell growth, and cell migration and invasion in HPV-transformed cells. In the tumorigenesis and lung metastasis model in syngeneic mice, depletion of LKB1 markedly increased tumor metastatic colonies in lungs without affecting subcutaneous tumor growth. We showed that HPV16 E6/E7 enhanced the expression of hexokinase-ll (HK-II) in the glycolytic pathway through elevated c-MYC. Ectopic LKB1 reduced HK-II along with glycolysis. The inverse relationship between HK-II and LKB1 was also observed in normal and HPV-associated cervical lesions. We propose that LKB1 acts as a safeguard against HPV-stimulated aerobic glycolysis and tumor progression. These findings may eventually aid in the development of therapeutic strategy for HPV-associated malignancies by targeting cell metabolism.

LKB1 reduces ROS-mediated cell damage via activation of p38.

Liver kinase B1 (LKB1, also known as serine/threonine kinase 11, STK11) is a tumor suppressor mutated in Peutz-Jeghers syndrome and in a variety of sporadic cancers. Herein, we demonstrate that LKB1 controls the levels of intracellular reactive oxygen species (ROS) and protects the genome from oxidative damage. Cells lacking LKB1 exhibit markedly increased intracellular ROS levels, excessive oxidation of DNA, increased mutation rates and accumulation of DNA damage, which are effectively prevented by ectopic expression of LKB1 and by incubation with antioxidant N-acetylcysteine. The role of LKB1 in suppressing ROS is independent of AMP-activated protein kinase, a canonical substrate of LKB1. Instead, under the elevated ROS, LKB1 binds to and maintains the activity of the cdc42-PAK1 (p21-activated kinase 1) complex, which triggers the activation of p38 and its downstream signaling targets, such as ATF-2, thereby enhancing the activity of superoxide dismutase-2 and catalase, two antioxidant enzymes that protect the cells from ROS accumulation, DNA damage and loss of viability. Our results provide a new paradigm for a non-canonical tumor suppressor function of LKB1 and highlight the importance of targeting ROS signaling as a potential therapeutic strategy for cancer cells lacking LKB1.

[Studies on the rare earth content in food and its daily intake in man].

The rare earth content of major food in China, they are distributed over 17 provinces and cities were examined by three-wavelength spectrophotometry. The rare earth contents were as follows: 0.41 +/- 0.35 mg/kg in grain, 0.23 +/- 0.18 mg/kg in vegetables, 0.19 +/- 0.11 mg/kg in fruits, 0.83 +/- 0.73 mg/kg in beans, 0.66 +/- 0.50 mg/kg in potato, 1.76 +/- 0.23 mg/kg in tea, 0.07 +/- 0.05 mg/kg in meat, birds, domestic fowls and eggs, 0.52 +/- 0.12 mg/kg in aquatic animals, 5.11 +/- 8.68 micrograms/L in drinking water. The possible daily intake of rare earth for a person from common foodstuffs was about 2.10-2. 50 mg/person.day, which was about one tenth to one sixth of ADI allowable daily intake of rare earths for a person.