Oesophageal carcinoma with solitary patellar metastasis: a rare case report

The incidence of tumours found in the patella, including primary and metastatic tumours, is low. Solitary metastasis of oesophageal carcinoma (OC) in the patella is even rarer. A 50-year-old man presented to our clinic because of pain and limited range of motion in the right knee for 4 hours and after a fall. On the basis of the patient’s medical history, he was diagnosed with OC 2 months previously and underwent two cycles of paclitaxel liposome combined with tiggio chemotherapy (oral tiggio, 40 mg, two times/day, with a treatment cycle of 3 weeks). A 99mTc-methylene diphosphonate bone scintigraphy scan showed increased radioactivity in the right patella. A right knee biopsy showed the presence of patellar metastasis from OC. Unfortunately, the patient denied additional treatment and was discharged for personal reasons. At the 1-month follow-up, which was conducted by a telephone survey, we learned that the patient had died of acute pulmonary embolism. X-rays and computed tomography are useful for diagnosing patellar metastases, but 99mTc-methylene diphosphonate bone scintigraphy can help physicians diagnose patellar metastasis of OC more rapidly. Biopsy with pathology is the gold standard for diagnosing patellar metastases. Additionally, timely surgical treatment prolongs the survival time of these patients.

Population Pharmacokinetics and Exposure–Safety Relationship of Paclitaxel Liposome in Patients With Non-small Cell Lung Cancer

PurposePaclitaxel liposome (Lipusu) is the first commercialized liposomal formulation of paclitaxel. There has been little data collected on the pharmacokinetics (PK) of paclitaxel liposome, especially in relation to patient use. This study aimed to build a population pharmacokinetic (PopPK) model and further explore the exposure–safety relationship for paclitaxel liposome in patients with non-small cell lung cancer (NSCLC).MethodsData from 45 patients with a total of 349 plasma concentrations were analyzed. The PopPK model was built using the non-linear mixed effect modeling technique.ResultsThe PK of paclitaxel liposome were well described by a three-compartment model with first-order elimination. For a dose of 175 mg m–2, the estimated clearance of total plasma paclitaxel was 21.55 L h–1. Age, sex, body weight, total bilirubin, albumin, serum creatinine, and creatinine clearance did not influence the paclitaxel PK. Exposure to paclitaxel had no significant change in the presence of the traditional Chinese medicine, aidi injection. The exploratory exposure–safety relationship was well described by a generalized linear regression model. Higher probabilities of grade >1 neutropenia were observed in patients with higher exposure to paclitaxel.ConclusionThis PopPK model adequately described the PK of paclitaxel liposome in patients with NSCLC. Predicted exposure of paclitaxel did not change in the presence of the traditional Chinese medicine, aidi injection. The exposure–safety analysis suggested that a higher risk of neutropenia was correlated with higher exposure to paclitaxel.

lncCRLA enhanced chemoresistance in lung adenocarcinoma that underwent epithelial-mesenchymal transition

EMT confers increased metastatic potential and the resistance to chemotherapies to cancer cells. However, the precise mechanisms of EMT-related chemotherapy resistance remain unclear. c-Src-mediated Caspase-8 phosphorylation essential for EMT in lung adenocarcinoma cell lines preferentially occurs in cells with the mesenchymal phenotype, resulting in chemoresistance to cisplatin plus paclitaxel inpatients with resectable lung adenocarcinoma and a significantly worse 5-year PFS. Cisplatin killed lung adenocarcinoma cells regardless of Caspase-8. Paclitaxel-triggered necroptosis in lung adenocarcinoma cells was dependent on the phosphorylation or deficiency of Caspase-8, during which FADD interacted with RIPK1 to activateRIPK1/RIPK3/MLKL signaling axis. Accompanied with c-Src-mediated Caspase-8 phosphorylation to trigger EMT, a novel lncRNA named lncCRLA was markedly upregulated and inhibited RIPK1-induced necroptosis by impairing RIPK1-RIPK3 interaction via binding to the intermediate domain of RIPK1. Dasatinib mitigated c-Src-mediated phosphorylation of Caspase-8-induced EMT and enhanced necroptosis in mesenchymal-like lung adenocarcinoma cells treated with paclitaxel, while c-FLIP knockdown predominantly sensitized the mesenchymal-like lung adenocarcinoma cells to paclitaxel+dasatinib. c-Src-Caspase-8 interaction initiates EMT and chemoresistance viaCaspase-8 phosphorylation and lncCRLA expression, to which the dasatinib/paclitaxel liposome+siFLIP regimen was lethal.