Cancer metastasis is the most dangerous stage of tumorigenesis and evolution, the primary cause of death in cancer patients. Clinically, more than 60% of cancer patients have found metastasis at the time of examination. Modern medicine has made significant progress on the mechanisms of cancer metastasis in recent years, from the simple "anatomy and machinery" theory forward to the "seed and soil" theory, then to the "microenvironmental" theory and the "cancer stem cell" theory. The emerging "cancer stem cell" theory successfully explains phenomenon such as tumor genetic heterogeneity, anoikis resistance, tumor dormancy, providing more new targets and ideas for the diagnosis and treatment of cancer metastasis.
Animals ; Humans ; Medicine ; methods ; Neoplasm Metastasis ; Neoplasms ; drug therapy ; pathology

Objective To explore the effects of different degrees of intermittent hypoxia (IH) on the activation and the secretion of extracellular matrix in MLg lung fibroblast cell line. Methods MLg lung fibroblast cells in logarithmic growth phase were exposed for 5%O2 for 100 seconds and 21%O2 for 120 seconds in 1 h, 4 h and 8 h groups (IH1, IH4 and IH8) and normoxia group (21%O2 for 8 h, N group). The cells in each group were collected at the end of experiment. Real-time PCR was used to measure the mRNA expression levels ofα-SMA and typeⅠcollagen (COL1) A1, and Western blot assay was used to detect the protein expression levels ofα-SMA and COL1. Results The mRNA and protein expression levels ofα-SMA and COL1 were significantly increased in IH1, IH4 and IH8 groups than those in N group (all P < 0.05). Furthermore, expression levels of α-SMA and COL1 showed a time-dependent increase with IH exposure time. Conclusion The intermittent hypoxia can promote the cell activation and the extracellular matrix secretion of mouse lung fibroblast cells, which may be related with the oxidative stress.

Objective To explore the effects of cobalt chloride (CoCl2)-induced hypoxia on migration of melanoma cells, and to detect the transcription, expression and secretion of Follistatin-like 1(FSTL1) in this process. Methods B16F10 melanoma cell line was treated with CoCl2 in order to mimic hypoxia. Experimental cells were divided into three groups: 0μmol/L, 50μmol/L and 100μmol/L CoCl2 treatment groups. MTT assay was used to assure cell viability, and to determine the treatment concentration of CoCl2. Transwell assay was used to determine the migration ability of B16F10 melanoma cell line. Real-time PCR was used to measure the mRNA expression of Fstl1. Western blot assay was used to detect the intracel?lular and extracellular protein expression of FSTL1. Results The cell viability of B16F10 melanoma cell line was signifi?cantly reduced by CoCl2 treatment, with a time and concentration-dependent manner. The migration ability of B16F10 cell line was significantly increased in CoCl2 treated group compared with that of control group (P<0.05). The mRNA level of Fstl1 was obviously higher in CoCl2 treated group than that of control group (P<0.05). The intracellular expression of FSTL1 protein was consistent with the expression trend of Fstl1 mRNA. Simultaneously, the extracellular protein level of FSTL1 was significantly decreased compared with that of control group. There was no expression of FSTL1 in 100μmol/L CoCl2 treat?ment group. Conclusion The migration ability of melanoma cell line is enhanced by CoCl2 treatment, which may be associ?ated with expression and secretion of FSTL1, however, the relevant mechanism still needs further investigation.

In this paper, three kinds of chemotactic parameters (concentration, temperature and pH) were determined by plate assay and spore germination method to research the chemotactic response of Botrytis cinerea and Alternaria panax, and their spores on total ginsenosides. The results showed that Botrytis cinerea had strong chemotactic response at the mid-concentration of total ginsenosides (cultivation temperature was 20 degrees C and pH value was 6), and the data of chemotactic migration index (CMI) was 1.293 0, chemotactic growth rate (CGR) was 0.476 0, spore germination rate (SGR) was 53%, and dry weight of mycelial (DWM) was 0.452 6 g x L(-1); however, Alternaria panax had strong chemotactic response at the low-concentration of total ginsenosides (cultivation temperature was 25 degrees C and pH value was 6), and the data of chemotactic migration index (CMI) was 1.235 4, chemotactic growth rate (CGR) was 0.537 0, spore germination rate (SGR) was 67%, and dry weight of mycelial (DWM) was 0.494 8 g x L(-1). The results indicated that the low and middle concentration (2, 20 mg x L(-1)) of total ginsenosides had significant promoting effect on chemotactic response of these two pathogens, and the spore germination, mycelial growth rate, dry weight of mycelial of them were also significantly improved by this chemotactic response, whereas it decreased as the increase of total ginsenosides concentration.
Alternaria ; drug effects ; growth & development ; physiology ; Botrytis ; drug effects ; growth & development ; physiology ; Chemotaxis ; drug effects ; Drugs, Chinese Herbal ; metabolism ; pharmacology ; Ginsenosides ; metabolism ; pharmacology ; Panax ; metabolism ; microbiology ; Plant Diseases ; microbiology ; Spores, Fungal ; drug effects ; growth & development ; physiology

OBJECTIVETo evaluate the long-term efficacy and safety of endoscopic tissue adhesive(N-octyl-α-cyanoacrylate) injection for the treatment of gastric varices.

METHODSA retrospective study was performed to review the clinical and follow up data of 169 patients with gastric variceal who received tissue adhesive injection at the Fudan University Affiliated Zhongshan Hospital between April 2004 and December 2011.

RESULTSThere were 128 males and 41 females with a mean age of 56.8(37-85) years old. One hundred and thirty-one patients received one injection, 38 received two injections or more with a mean of 1.12 per patient. Volume of injection ranged from 1 to 3 ml(mean, 1.7 ml). Eighty-three patients received adhesive injection alone, 231 received injection combined with ligation, 50 received combined sclerotic agent injection. All the patients had follow up ranging from 1 to 78 months(mean, 3.4 months). The treatment outcome was satisfactory in 130 patients(76.9%), good in 36(21.3%), and ineffective in 3(1.8%). The rate of ectopic embolization was 3.0%, and the rate of early re-bleeding was 1.2%. Postoperatively there were no septic complications or esophageal stricture. There were no deaths within 2 weeks.

CONCLUSIONInjection of tissue adhesive under endoscopic guidance for treatment of gastric varices is convenient, safe and effective.

Adult ; Aged ; Aged, 80 and over ; Esophageal and Gastric Varices ; therapy ; Female ; Follow-Up Studies ; Gastroscopy ; Humans ; Injections, Intralesional ; Male ; Middle Aged ; Retrospective Studies ; Tissue Adhesives ; administration & dosage ; therapeutic use ; Treatment Outcome

OBJECTIVETo sought to engineer and characterize a biodegradable nanoparticles (NPs) containing rapamycin which use poly (lactic-co-glycolic) acid (PLGA) as the carrier matrix and to assess its in vivo release characteristics by local drug delivery system intravascularly.

METHODSRapamycin-loaded PLGA NPs were prepared by an emulsification/solvent evaporation technique, and NPs size distribution was assessed by submicro laser defractometer. The particle morphology was observed by scanning electron microscopy. In vitro release from the NPs was performed in TE buffer at 37 degrees C under rotation utilizing double-chamber diffusion cells on a shake stander. In vivo NPs intravascular local delivery were performed by DISPATCH catheter in New Zealand rabbit abdominal aorta and Chinese experimental mini-pigs coronary artery models.

RESULTSBiodegradable rapamycin loaded PLGA NPs were constructed successfully by emulsification solvent-evaporation technique. The diameter of rapamycin-PLGA NPs was around 246.8 nm with very narrow size distribution, and rapamycin-NPs showed good spherical shape with smooth uniform surface. Rapamycin loaded in NPs were around was 19.42%. Encapsulation efficiency of drug was over 77.53%. The in vitro release of rapamycin from NPs showed that 75% of the drug was sustained released over 2 weeks and controlled release in a linear pattern. After a single 10 minutes infusion of rapamycin-PLGA NPs suspension (5 mg/ml) under 20.27 kPa through DISPATCH catherter in vivo, the mean rapamycin levels at 7 day and 14 day were (2.438 +/- 0.439) and (0.529 +/- 0.144) microg/mg of the dry-weight of the artery segments (2 cm) which local delivery were administrated.

CONCLUSIONSPLGA NPs controlled drug delivery system for intraarterial local anti-proliferative drug delivery can potentially improve local drug concentration and prolong drug residence time in animal model in vivo. It should be appropriate for further study of its therapy efficiency in human.

Animals ; Aorta, Abdominal ; drug effects ; Coronary Vessels ; drug effects ; Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Infusions, Intra-Arterial ; Lactic Acid ; chemistry ; Nanoparticles ; chemistry ; Particle Size ; Polyglycolic Acid ; chemistry ; Rabbits ; Sirolimus ; administration & dosage ; pharmacokinetics ; Swine ; Swine, Miniature

Ongoing study on the chemical constituents of the roots of Macleaya microcarpa led to the isolation of eight compounds of derivatives of triterpenes and organic acids in addition to some previously identified benzophenanthridines. The eight compounds were identified by spectroscopic methods as well as comparison with literature values as 1-oxo-2, 22 (30)-hopandien-29-oic acid (1), 3-oxo-12-oleanen-30-oic acid (2), 3α-hydroxy-12-oleanen-30-oic acid (3), 3β-hydroxy-12-oleanen-30-oic acid (4), ferulic acid (5), ferulic acid 4-O-β-D-glucoside (6), 3-O-feruloylquinic acid (7), and methyl 3-O-feruloylquinate (8). Of which, 1 is a new triterpenoid of hopanes and 2-8 are isolated from M microcarpa for the first time. In order to discover natural active compounds as potential agents of anti-ulcerative colitis (UC), an in vitro drug high-throughput screening model targeted x-box-binding protein 1 (xbp1) was employed to evaluate the activity of the major chemical constituents of M microcarpa. The result confirmed that two dihydrobenzophenanthridines, dihydrosanguinarine (9) and dihydrochelerythrine (10), showed a certain activity on activating the transcription of xbpl, a transcription factor (TF) associated with the occurrence, development, and potential treatment of UC, with their relative activating ratios being 1.76 and 1.77 times, respectively, as compared with control group.
Anti-Ulcer Agents ; chemistry ; Benzophenanthridines ; chemistry ; DNA-Binding Proteins ; genetics ; Isoquinolines ; chemistry ; Papaveraceae ; chemistry ; Plant Roots ; chemistry ; Regulatory Factor X Transcription Factors ; Transcription Factors ; genetics ; Transcription, Genetic ; Triterpenes ; chemistry

This study was aimed to explore the difference of NK cell receptor NKG2D and NKG2A expression on NK cells and CD3(+) T cells and their ligand MHC-I A/B (major histocompatibility complex class I-related chains A/B) and HLA-E expression in leukemia cells, as well as its immunological significance. Flow cytometry was used to detect the killing rate of NK92 cells to 8 leukemia cell lines, and the expression of NKG2D and NKG2A on NK cells and CD3(+) T cells as well as their ligand MHC-I A/B and HLA-E expression on leukemia cells. The results indicated that the NK92 showed different killing activity to different leukemia cell lines. The positive expression rate of NKG2D and NKG2A on NK cells and CD3(+) T cells in ALL patients was no significantly different from that in AML patients (p > 0.05), but positive expression rate of MHC-I A/B and HLA-E in ALL patients was obviously higher than that in AML patients (p < 0.05). It is concluded that there is difference of immune cell function between ALL and AML patients, this difference may be associated with the expression difference of NKG2D and NKG2A ligands on leukemia cells while does not associated with the killing and inhibiting receptors expressed on NK cells and CD3(+) T cells.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Histocompatibility Antigens Class I ; genetics ; metabolism ; Humans ; Infant ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Male ; Middle Aged ; NK Cell Lectin-Like Receptor Subfamily C ; genetics ; metabolism ; NK Cell Lectin-Like Receptor Subfamily K ; genetics ; metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; metabolism ; Young Adult

OBJECTIVE To identify the valid targets and new drugs of ulcerative colitis (UC), a recurrent and intractable inflammatory bowel disease. METHODS and RESULTS In an in vivo mouse model of DSS-induced colitis, HLJ2 decreased weight loss, colon contracture, disease activity index (DAI), colon mucosa damage index (CMDI) and histopathological index (HI). HLJ2 also decreased myelo?peroxidase(MPO) activity and reduced production of the inflammatory cytokines TNF- α, IL- 1β, andIL- 6. HLJ2 improved intestinal mucosa damage induced by dextran sodium sulfate (DSS) and increased the expression of ZO-1 and claudin-1. Fecal 16s rRNA high-throughput sequencing demon?strated a significant improvement in UC intestinal dysbacteriosis in mice treated with HLJ2, including increased abundance of probiotics such as Lachnospiraceae, Prevotellaceae, and Lactobacillaceae. At the same time there was a reduction in the abundance of pathogenic or conditional pathogenic microor?ganisms such as Bacteroidaceae, Porphyromonadaceae, Deferribacteraceae, and Pseudomonadaceae in HLJ2- treated mice compared with untreated mice. CONCLUSION Our results demonstrated that the XBP1 agonist HLJ2 inhibits inflammation, regulates the intestinal flora, and protects the intestinal mucosa. It is thus a potential therapeutic agent for ulcerative colitis.

Taking application of some isolation and purification technologies, including crushing, solvent extraction, preliminary solvent isolation, column chromatographies over silica gel and Sephadex LH-20 gel and preparative HPLC, 8 compounds were obtained from the seeds of Jufeng grape sourced from market. Their structures were identified by spectroscopic methods and comparison with literature values as Catechin (1), Epicatechin (2), quercetin (3), ethylgallate (4), rel-(2S, 3R) -2-(4-hydroxy-3-methoxyphenyl) -3- (hydroxymethyl)-5-(3-hydroxypropyl)-2,3-dihydrobenzofuran-7-ol (5), rel-(2α, 3β)-7-O-methylcedrusin (6), rel-(1R,2S)-1-(4-hydroxy-3-methoxyphenyl) -2-(4-(3-hydroxypropyl) -2-methoxyphenoxy) propane-1,3-diol (7), and (+) -isolariciresinol (8), respectively. Compounds 5-8 were serial lignans isolated from the seeds of grape for the first time. Structurally, 5 and 6 belong in benzofuran-8,3'-neolignans, 7 in 8,4'-oxyneolignan, and 8 in 8,8' :2,7'-cyclolignan. According to in vitro activity evaluation conducted in cell model, compound 6 showed significant anti-oxidative ability, with the activity of RAW264. 7 cell superoxide dismutase being raised evidently in the test as compared with the positive anti-oxidative agents, compounds 1 and 2.
Antioxidants ; chemistry ; isolation & purification ; Magnetic Resonance Spectroscopy ; Plant Extracts ; chemistry ; isolation & purification ; Seeds ; chemistry ; Vitis ; chemistry