Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer

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Molecular cloning and expression pattern of 11 genes involved in lipid metabolism in yellow catfish Pelteobagrus fulvidraco

11 genes involved in lipid metabolism were cloned from liver of yellow catfish Pelteobagrus fulvidraco, including CPT 1A, CPT 1B, PPARα, PPARγ, SREBP-1, G6PD, 6PGD, FAS, acetyl-CoA ACCa, ACCb, and LPL. Phylogenetic analysis further identified these genes, and confirmed the classification and evolutionary status of yellow catfish. mRNA of all eleven genes was present in liver, muscle, mesenteric adipose, ovary and heart, but at varying levels. The present study will facilitate further studies on the regulation of lipid metabolism at the molecular level for the fish species.     

Integrated pharmacokinetic,pharmacodynamic and immunogenicity profiling of an anti-CCL21 monoclonal antibody in cynomolgus monkeys

QBP359 is an IgG1 human monoclonal antibody that binds with high affinity to human CCL21, a chemokine hypothesized to play a role in inflammatory disease conditions through activation of resident CCR7-expressing fibroblasts/myofibroblasts. The pharmacokinetics (PK) and pharmacodynamics (PD) of QBP359 in non-human primates were characterized through an integrated approach, combining PK, PD, immunogenicity, immunohistochemistry (IHC) and tissue profiling data from single- and multiple-dose experiments in cynomolgus monkeys. When compared with regular immunoglobulin typical kinetics, faster drug clearance was observed in serum following intravenous administration of 10 mg/kg and 50 mg/kg of QBP359. We have shown by means of PK/PD modeling that clearance of mAb-ligand complex is the most likely explanation for the rapid clearance of QBP359 in cynomolgus monkey. IHC and liquid chromatography mass spectrometry data suggested a high turnover and synthesis rate of CCL21 in tissues. Although lymphoid tissue was expected to accumulate drug due to the high levels of CCL21 present, bioavailability following subcutaneous administration in monkeys was 52%. In human disease states, where CCL21 expression is believed to be expressed at 10-fold higher concentrations compared with cynomolgus monkeys, the PK/PD model of QBP359 and its binding to CCL21 suggested that very large doses requiring frequent administration of mAb would be required to maintain suppression of CCL21 in the clinical setting. This highlights the difficulty in targeting soluble proteins with high synthesis rates.     

Apatinib for heavily treated patients with non-small cell lung cancer: Report of a case series and literature review

Although many strategies have been developed for non-small cell lung cancer (NSCLC), more secondary and further treatments are needed due to drug resistance or tumor recurrence. Apatinib is a novel oral antiangiogenic agent and in this study, we aim to investigate the clinical value of apatinib in heavily pretreated NSCLC. Here, we reported the characteristics, efficacy and adverse events of three patients treated with apatinib (500?mg/day). We also summarized the currently available evidence and ongoing clinical trials regarding the use of apatinib in NSCLC. Two cases of adenocarcinoma and one case of squamous cell carcinoma were treated with apatinib due to disease progression after previous treatments of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). All patients responded to apatinib rapidly and underwent drug resistance shortly afterwards. The patient with squamous cell carcinoma died of hemoptysis. Other adverse events were acceptable. All previous relevant studies were compared and showed similar results but a longer progression-free survival. Additionally, ongoing clinical trials were systematically searched and listed. In conclusion, apatinib shows some efficacy in heavily treated NSCLC and generally tolerable toxicity in non-squamous NSCLC. More solid evidence will be accessible in near future.