Analyzing resistance pattern of non-small cell lung cancer to crizotinib using molecular dynamic approaches.

Crizotinib is the potential anticancer drug used for the treatment of non-small cell lung cancer (NSCLC) approved by FDA in 2011. The main target for the crizotinib is anaplastic lymphoma kinase (ALK). Evidences available indicate that double mutant ALK (L1196M and G1269A) confers resistance to crizotinib. However, how mutation confers drug resistance is not well-understood. Hence, in the present study, molecular dynamic (MD) simulation approach was employed to study the impact of crizotinib binding efficacy with ALK structures at a molecular level. Docking results indicated that ALK double mutant (L1196M and G1269A) significantly affected the binding affinity for crizotinib. Furthermore, MD studies revealed that mutant ALK-crizotinib complex showed higher deviation, higher fluctuation and decreased number of intermolecular H-bonds, when compared to the native ALK-crizotinib complex. These results may be immense importance for the molecular level understanding of the crizotinib resistance pattern and also for designing potential drug molecule for the treatment of lung cancer.

Pancreatitis, polyarthritis, panniculitis syndrome’ (PPP syndrome) plus prolonged pyrexia–a rare presentation of chronic pancreatitis.

Pancreatitis presenting without abdominal pain is very unusual. Here we report a 70-year-old man with chronic calcific pancreatitis presented to us with prolonged fever, arthritis and multiple subcutaneous swellings, but without any abdominal pain or other abdominal symptoms. His serum amylase and lipase were very high. Biopsy from the subcutaneous swellings revealed fat necrosis and CT scan abdomen showed features of chronic calcific pancreatitis. He was managed conservatively with supportive measures, and recovered. There is only scanty information in literature regarding this type of presentation in chronic pancreatitis.