Preclinical PK/PD model for combined administration of erlotinib and sunitinib in the treatment of A549 human NSCLC xenograft mice.

Aim: Combined therapy of EGFR TKI and VEGFR TKI may produce a greater therapeutic benefit and overcome EGFR TKI-induced resistance. However, a previous study shows that a combination of EGFR TKI erlotinib (ER) with VEGFR TKI sunitinib (SU) did not improve the overall survival in patients with non-small-cell lung cancer (NSCLC). In this study we examined the anticancer effect of ER, SU and their combination in the treatment of A549 human NSCLC xenograft mice, and conducted PK/PD modeling and simulations to optimize the dose regimen.

Mast cell activation is involved in stress-induced epithelial barrier dysfunction in the esophagus.

Objective: We aimed to investigate the role of mast cell in stress-induced barrier dysfunction in the esophagus and its possible pathway involved using mast cell-deficient (Ws/Ws) rats.

Methods: Ws/Ws rats and normal (+/+) rats were submitted to chronic restraint stress (CRS) 2 h/day for 7 days. Tissues were obtained from distal esophagus.

[Reconstitution of mast cell population in gastrointestinal tract by bone marrow transplantation in mast cell deficient rats].

Objective: To explore whether bone marrow transplantation (BMT) can restore gastrointestinal mast cells in mast cell deficient (Ws/Ws) rats and understand the features of these reconstituted mast cells.

Methods: Thirty-six Ws/Ws rats were subjected to Co(60) radiation at 6 gradient doses (6.0, 7.

[Establishment of irritable bowel syndrome rat model by combination of intestinal infection with Trichinella spiralis and acute stress].

Objective: To establish the irritable bowel syndrome (IBS) rat model by the combination of acute stress and transient intestinal infection with Trichinella spiralis (T.S.).

Alteration of cholinergic and peptidergic neurotransmitters in rat ileum induced by acute stress following transient intestinal infection is mast cell dependent.

Background: Mast cells are implicated in the development of irritable bowel syndrome (IBS), which is associated with the activation of the "neural-immune" system. The aim of this study was to investigate the role of mast cells in the remodeling of cholinergic and peptidergic neurotransmitters induced by acute cold restriction stress (ACRS) post infection (PI) using mast cell deficient rats (Ws/Ws) and their wild-type controls (+/+).

Methods: Transient intestinal infection was initiated by giving 1500 Trichinella spiralis (T.

Identification of new cytotoxic T-lymphocyte epitopes from cancer testis antigen HCA587.

The cancer testis (CT) antigen HCA587 is highly expressed in human hepatocellular carcinoma (HCC) and induces specific T-cell responses in a significant proportion of HCC patients. To explore its potential in cancer immunotherapy, a reverse immunology approach was adopted to identify HCA587-derived HLA-A( *)0201-restricted epitopes. Multiple peptides with a top ranking in various prediction programs were thus synthesized and three of them-p248-256, p140-149 and p144-152-were found to bind to HLA-A(*)0201 molecules with a high affinity and effectively induced a recall response of CD8+ T cells, which were either primed in vitro with the HCA587 antigen or directly isolated from HCC patients bearing HCA587+ tumors.