Oral immunotherapy with enteric-coated capsules for allergic rhinitis caused by house dust mites.

Background: Oral immunotherapy (OIT) is a promising allergen-specific approach in the management of food allergy; however, studies on OIT for allergic rhinitis (AR) have rarely been reported. The purpose of this study is to evaluate the efficacy and safety of OIT using enteric-coated capsules for AR induced by house dust mites.

Methods: A total of 49 patients with AR were enrolled, including 25 who received subcutaneous immunotherapy (SCIT) and 24 who received OIT.

Correlation of deregulated like-acetylglucosaminyl transferase and aberrant α-dystroglycan expression with human tongue cancer metastasis.

Purpose: The present study examined the correlation of α-dystroglycan (α-DG) expression and like-acetylglucosaminyl transferase (LARGE) with metastasis of human tongue cancer.

Materials And Methods: Fifty human tongue cancer tissues and 2 tongue squamous cell carcinoma cell lines (CAL27 and SCC4) were involved. Immunohistochemistry was used to detect the expression of α-DG and LARGE.

[Evaluation of safety of meningococcal group AC bivalent polysaccharide conjugate vaccine in children aged 5-24 months old].

Objective: To evaluate the safety of meningococcal group AC bivalent polysaccharide conjugate vaccine among children aged 5-24 months old.

Methods: From July 2011 to June 2012, a total of 34 411 children aged 5-24 month-old who voluntarily vaccinated meningococcal group AC bivalent polysaccharide conjugate vaccine in Zhongshan city were included. The adverse effects within 72 hours were recorded and analyzed.

Alterations of high endothelial venules in primary and metastatic tumors are correlated with lymph node metastasis of oral and pharyngeal carcinoma.

High endothelial venules (HEVs) are special blood vessels in the paracortical region of lymph nodes (LNs) and govern lymphocyte recruitment. LN metastasis has similarity to circulating lymphocytes homing to LNs, but the role of HEVs in the progression of oral and pharyngeal squamous cell carcinoma (OPSCC) is unclear. In this study, we found that HEVs experienced a series of morphological and functional changes during OPSCC progression and were correlated with LN metastasis.

[Experimental study on ectopic prefabrication of vascularized mandible graft with autogenous ribs].

Objective: To explore a method for ectopic prefabrication of mandible with vascular pedicle.

Methods: Cancellous bone blocks harvested from the dog ribs were packaged with mandible-shaped titanium mesh scaffold and implanted into latissimus dorsi of dog with thoracodorsal artery and vein through the scaffold. After 12 weeks, bone formation and vascularization were evaluated by gross inspection, histological examination and immunohistochemistry.

Tumor necrosis factor-α enhanced fusions between oral squamous cell carcinoma cells and endothelial cells via VCAM-1/VLA-4 pathway.

Fusion between cancer cells and host cells, including endothelial cells, may strongly modulate the biological behavior of tumors. However, no one is sure about the driving factors and underlying mechanism involved in such fusion. We hypothesized in this study that inflammation, one of the main characteristics in tumor microenvironment, serves as a prominent catalyst for fusion events.

Discovery of 3-aryl-5-aryl-1,2,4-oxadiazoles as a new series of apoptosis inducers. 2. Identification of more aqueous soluble analogs as potential anticancer agents.

As a continuation of our efforts to discover and develop the 3-aryl-5-aryl-1,2,4-oxadiazole series of apoptosis inducers as potential anticancer agents, we explored substitutions at the 2- and 3-positions of the 3-aryl group to improve the aqueous solubility properties and identify development candidates. A small substitution such as methyl or hydroxymethyl at the 2-position was well tolerated. This modification, in combination with a 3-substituted furan ring as the 5-aryl group, resulted in 4g and 4h, which have improved solubility properties.

Discovery and structure-activity relationships of (2-(arylthio)benzylideneamino)guanidines as a novel series of potent apoptosis inducers.

1-(2-(2,5-Dimethoxyphenylthio)benzylidene)semicarbazide (2a) was discovered as a potent apoptosis inducer through our cell based HTS assay. SAR study led to the discovery of a more aqueous soluble analog (2-(2,5-dimethoxyphenylthio)-6-methoxybenzylideneamino)guanidine (5e) with EC(50) value of 60 nM in the caspase activation assay and GI(50) value of 62 nM in the growth inhibition assay in T47D cells. Compound 5e was found to be an inhibitor of tubulin polymerization and efficacious in a MX-1 breast tumor model.

Selective activation of apoptosis by a novel set of 4-aryl-3-(3-aryl-1-oxo-2-propenyl)-2(1H)-quinolinones through a Myc-dependent pathway.

Oncogene addiction due to Myc deregulation has been identified in a variety of tumor types. In order to identify pharmacological agents that cause selective apoptosis in tumors with deregulated Myc expression, we designed a cell-based screening assay based on our Anti-cancer Screening Apoptosis Program (ASAP) technology targeting increased activity in a "Myc-addicted" cancer cell panel. We have identified a novel set of substituted 4-aryl-3-(3-aryl-1-oxo-2-propenyl)-2(1H)-quinolinones that activates apoptosis in cancer cell lines with deregulated Myc, but show low activity in cell lines where Myc is not deregulated.

Discovery of 1-benzoyl-3-cyanopyrrolo[1,2-a]quinolines as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. Part 1: Structure-activity relationships of the 1- and 3-positions.

1-Benzoyl-3-cyanopyrrolo[1,2-a]quinoline (2a) was identified as a novel apoptosis inducer through our caspase- and cell-based high-throughput screening assay. Compound 2a had good activity against several breast cancer cell lines but was much less active against several other cancer cell lines. SAR studies of 2a found that substitution at the 4-position of the 1-benzoyl group was important for activity.

Discovery and structure-activity relationship of N-phenyl-1H-pyrazolo[3,4-b]quinolin-4-amines as a new series of potent apoptosis inducers.

We report the discovery and SAR study of a series of N-phenyl-1H-pyrazolo[3,4-b]quinolin-4-amines as potent inducers of apoptosis. N-(3-Acetylphenyl)-2,3-dihydro-1H-cyclopenta[b]quinolin-9-amine (2) was discovered through our cell- and caspase-based HTS assays as an inducer of apoptosis. Compound 2 is active against cancer cells derived from several human solid tumors, with EC(50) values ranging from 400 to 700 nM.

[Evaluation on schistosomiasis control effect of the intervention measures adapted to the ecological environment changes in Jiang Han Plain due to establishment of the Three Gorges dam].

Objective: To evaluate the effect of the intervention measures for schistosomiasis control adapted to the ecological environment changes in Jiang Han plain caused by the establishment of the Three Gorges Dam.

Methods: Four villages in Qianjiang City were selected to implement paddy-upland rotation, crawfish-paddy alternation, water control and soil improvement, and adjusting agricultural structure to rebuild the waterlogging low yielding land and to change the snail habitat environment respectively. The snail habitat area, mean density of living snails and prevalence of schistosomiasis in human and cattle were compared with those of the control villages.

Design and synthesis of dipeptidyl glutaminyl fluoromethyl ketones as potent severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors.

This paper describes the design and synthesis of dipeptidyl N,N-dimethyl glutaminyl fluoromethyl ketones (fmk) as severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors. The compounds were tested against SARS-CoV-induced cell death in Vero or CaCo2 cells as a measurement of the inhibiting effects of the compounds on the replication of the virus. Z-Leu-Gln(NMe(2))-fmk (6a) was found to be a potent inhibitor with low toxicity in cells, protecting cells with an EC(50) value of 2.

A role for transferrin receptor in triggering apoptosis when targeted with gambogic acid.

Transferrin receptor (TfR) has been shown to be significantly overexpressed in different types of cancers. We discovered TfR as a target for gambogic acid (GA), used in traditional Chinese medicine and a previously undiscovered link between TfR and the rapid activation of apoptosis. The binding site of GA on TfR is independent of the transferrin binding site, and it appears that GA potentially inhibits TfR internalization.

Discovery and structure-activity relationship of 3-aryl-5-aryl-1,2,4-oxadiazoles as a new series of apoptosis inducers and potential anticancer agents.

We have identified 5-(3-chlorothiophen-2-yl)-3-(4-trifluoromethylphenyl)-1,2,4-oxadiazole (1d) as a novel apoptosis inducer through our caspase- and cell-based high-throughput screening assay. Compound 1d has good activity against several breast and colorectal cancer cell lines but is inactive against several other cancer cell lines. In a flow cytometry assay, treatment of T47D cells with 1d resulted in arrest of cells in the G(1) phase, followed by induction of apoptosis.

The discovery and mechanism of action of novel tumor-selective and apoptosis-inducing 3,5-diaryl-1,2,4-oxadiazole series using a chemical genetics approach.

A novel series of 3,5-diaryl-oxadiazoles was identified as apoptosis-inducing agents through our cell and chemical genetics-based screening assay for compounds that induce apoptosis using a chemical genetics approach. Several analogues from this series including MX-74420 and MX-126374 were further characterized. MX-126374, a lead compound from this series, was shown to induce apoptosis and inhibit cell growth selectively in tumor cells.

Discovery and SAR of indole-2-carboxylic acid benzylidene-hydrazides as a new series of potent apoptosis inducers using a cell-based HTS assay.

A series of indole-2-carboxylic acid benzylidene-hydrazides has been identified as a new class of potent apoptosis inducers through a novel cell-based caspase HTS assay. The screening hit, 5-chloro-3-methyl-indole-2-carboxylic acid (4-nitrobenzylidene)-hydrazide (3a), was found to arrest T47D cells in G(2)/M and to induce apoptosis as measured by the flow cytometric analysis assay. A SAR study was carried out by modification of the substitutions on the indole and benzene rings.

Discovery, characterization and SAR of gambogic acid as a potent apoptosis inducer by a HTS assay.

Gambogic acid (2), a natural product isolated from the resin of Garcinia hurburyi tree, was discovered to be a potent apoptosis inducer using our cell- and caspase-based high-throughput screening assays. Gambogic acid was found to have an EC(50) of 0.78 microM in the caspase activation assay in T47D breast cancer cells.

N-Ac-DEVD-N'-(Polyfluorobenzoyl)-R110: novel cell-permeable fluorogenic caspase substrates for the detection of caspase activity and apoptosis.

N-Pentafluorobenzoyl-R110 (1a) and N-(2,3,4,5-tetrafluorobenzoyl)-R110 (1b) with enhanced cell retention properties, were prepared from rhodamine 110 (R-110) and the corresponding polyfluorobenzoyl chloride. N-Ac-DEVD-N'-pentafluorobenzoyl-R110 (3a) and N-Ac-DEVD-N'-(2,3,4,5-tetrafluorobenzoyl)-R110 (3b) were prepared as tetrapeptide substrates for caspases. Substrate 3b was efficiently cleaved by human recombinant caspase-3 in an enzyme assay.

Structure-activity relationships for inhibition of human 5alpha-reductases by polyphenols.

The enzyme steroid 5 alpha-reductase (EC 1.3.99.