Targeting the unfolded protein response, XBP1, and the NLRP3 inflammasome in fibrosis and cancer
A castrated, 11.5-y-old, male greyhound had been diagnosed with a metastatic colorectal carcinoma five years prior. He had been extensively treated with multiple surgeries and courses of chemotherapy (carboplatin, adriamycin, 5-FU, cytoxan, palladia, masitinib, piroxicam, deramax, and leukeran) and had also undergone 3 treatments for rectal stricture with an internal medicine specialist. The mass had been biopsied 4 times during the course of the previous treatments, and all biopsies confirmed the continued presence of rectal carcinoma. By early 2013, the patient’s tumor began to grow and protrude externally around the anus to an extent that compromised the anal region.\nA board-certified surgeon evaluated the patient and determined that no further surgery should be performed. Given the lack of other treatment options, the patient was enrolled and received the first four doses of Naclynamide without incident. The tumor progressively decreased in size and began to suppurate. At this point the patient also began to lick at the tumor obscuring objective measurements of the tumor’s exterior appearance because of the consequent inflammation. Cytology was evaluated, and while there were still rafts of carcinoma cells present, the majority of the sample showed suppurative inflammation. Bacterial organisms were present, as would be expected based on tumor location. Internally, the patient’s rectal stricture improved markedly in diameter to approximately double that at the beginning of Naclynamide treatment. Initially on digital palpation, the rectal canal measured <5 mm in diameter but increased to approximately 1 cm during the course of treatment. The tumor itself shrank from 8 cm in its largest measurement to 4 cm.