Pneumocystis jirovecii diagnosed by next-generation sequencing of bronchoscopic alveolar lavage fluid: A case report and review of literature.

BACKGROUND: The advent of molecular targeted agents and immune checkpoint inhibitors has greatly improved the treatment of advanced renal cell carcinoma (RCC), thus significantly improving patient survival. The incidence of rare drug-related adverse events has gained increased attention. CASE SUMMARY: We report a patient with advanced RCC treated with multiple lines of molecular targeted agents and immune checkpoint inhibitors, who developed a pulmonary infection after treatment with everolimus in combination with lenvatinib. Determining the pathogenic organism was difficult, but it was eventually identified as Pneumocystis jirovecii by next-generation sequencing (NGS) of bronchoscopic alveolar lavage fluid (BALF) and successfully treated with trimethoprim-sulfamethoxazole. CONCLUSION: Rare pulmonary infections caused by molecular targeted agents are not uncommon in clinical practice, but their diagnosis is difficult. Evaluating BALF with NGS is a good method for rapid diagnosis of such infections.

Gene therapy with the angiogenesis inhibitor endostatin in an orthotopic lung cancer murine model.

Angiogenesis plays an important role in the growth of solid tumors. To date, no information has been acquired on the effectiveness of gene therapy in the orthotopic lung cancer model of syngeneic immunocompetent mice treated with an angiogenesis inhibitor. Here, we report the establishment of such a model in which Lewis lung carcinoma (LL/2) cell suspensions were orthotopically inoculated into the lung parenchyma of C57BL/6 mice, which were also injected with a recombinant adenoviral vector delivering the human endostatin gene (Ad-hE). We found that orthotopic implantation of LL/2 cells into the lung parenchyma produced a solitary tumor nodule in the lung followed by remote mediastinal lymph node metastasis. Conditioned medium from Ad-hE-transfected LL/2 cells apparently inhibited proliferation of human umbilical vein endothelial cells (HUVECs). The level of endostatin protein in serum could be identified by enzyme-linked immunosorbent assay. Treatment with Ad-hE resulted in inhibition of tumor growth and prolongation of survival time of tumor-bearing mice. Immunohistochemical analysis revealed that intratumoral angiogenesis was significantly suppressed. Furthermore, the finding of angiogenesis inhibition was also supported by measuring the number of circulating endothelial cells (CECs). Apoptotic cells were found to be increased within tumor tissues from mice treated with Ad-hE. In addition, treatment with Ad-hE combined with cis-diamminedichloroplatinum(II) (cisplatin) enhanced antitumor activity. These observations provide further evidence of the antitumor effect of endostatin gene therapy, and may be of importance for further exploration of potential application of this combined approach in the treatment of human lung cancer as well as other solid tumors.