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Background Our study and several studies have reported that in some cancers, including pancreatic ductal adenocarcinoma (PDAC), the expression of squamous lineage markers, such as esophagus-tissue-specific genes, correlated with a poor prognosis. However, the mechanism by which the acquisition of squamous lineage phenotypes leads to a poor prognosis remains unclear. We previously reported that retinoic acid signaling via retinoic acid receptor γ (RARγ signaling) determines the differentiation lineage into the esophageal squamous epithelium. These findings hypothesized that the activation of RARγ signaling contributed to acquiring squamous lineage phenotypes and malignant behavior in PDAC. Methods This study utilized public databases and immunostaining of surgical specimens to examine RARγ expression in PDAC. We evaluated the function of RARγ signaling by inhibitors and siRNA knockdown using a PDAC cell line and patient-derived PDAC organoids. The mechanism of the tumor-suppressive effects by blocking RARγ signaling was examined by a cell cycle analysis, apoptosis assays, RNA sequencing and Western blotting. Results RARγ expression in pancreatic intraepithelial neoplasia (PanIN) and PDAC was higher than that in the normal pancreatic duct. Its expression correlated with a poor patient prognosis in PDAC. In PDAC cell lines, blockade of RARγ signaling suppressed cell proliferation by inducing cell cycle arrest in the G1 phase without causing apoptosis. We demonstrated that blocking RARγ signaling upregulated p21 and p27 and downregulated many cell cycle genes, including cyclin-dependent kinase 2 (CDK2), CDK4 and CDK6. Furthermore, using patient-derived PDAC organoids, we confirmed the tumor-suppressive effect of RARγ inhibition and indicated the synergistic effects of RARγ inhibition with gemcitabine. Conclusions This study clarified the function of RARγ signaling in PDAC progression and demonstrated the tumor-suppressive effect of selective blockade of RARγ signaling against PDAC. These results suggest that RARγ signaling might be a new therapeutic target for PDAC.

Mycobacterium avium complex (MAC) is an important cause of opportunistic infections in immunosuppressed hosts, such as patients with HIV infection and solid organ transplant recipients. MAC disease usually presents in 4 distinct clinical categories: chronic pulmonary disease, disseminated disease, skin/soft-tissue infection, and superficial lymphadenitis. However, clinical reports on gastrointestinal (GI) MAC disease are rare, especially in patients without HIV infection or a history of organ transplantation. We describe a case of non-HIV-associated GI MAC disease in a patient with long-term mycophenolate mofetil use. In this case, MAC organisms in the GI tract and ascites were observed. Endoscopy revealed a unique colonic image with large, deep epithelial denudations. This suggests that apart from patients with HIV infection or transplant recipients, those treated with immunosuppressants can have disseminated MAC. Therefore, internal physicians need to monitor patients undergoing mycophenolate mofetil immunosuppressant therapy.

Additional file 1. SPIRIT checklist.

Table S1. A list of 44 probes upregulated by CSE exposure in both NHBEs and SAECs. Table S2. A list of 72 probes upregulated by CSE exposure only in SAECs. Table S3. A list of 39 probes upregulated by CSE exposure only in NHBEs. Table S4. A list of 23 probes downregulated by CSE exposure in both NHBEs and SAECs. Table S5. A list of 55 probes downregulated by CSE exposure only in SAECs. Table S6. A list of 71 probes downregulated by CSE exposure only in NHBEs. (DOCX 3206 kb)