By means of a simple mixing procedure, we have constructed cationic Sendai virosomes consisting of fusogenic viral F/HN proteins and cationic lipids. Sendai virus F/HN proteins were purified by Triton X-100 treatment and sequential centrifugation, and then quantitatively added to cationic liposomes. The presence of HN proteins is essential for hemolytic activity of Sendai virus as well as efficient gene transfection. The amount of detergent added for purification of F/HN proteins was also crucial for hemolytic activity. The relevance of F/HN proteins in the gene-transfer capability of the cationic Sendai F/HN virosomes (CSVs) was verified by heat inactivation of the F/HN proteins, and cell-binding competition. DNA condensation by protamine sulfate was able to further enhance the transfection efficiency and serum resistance of CSV. The enhanced transfection efficiency of protamine-condensed DNA-encapsulating cationic Sendai F/HN virosomes (PCSVs) may result from specific and efficient cell binding mediated by F/HN proteins and efficient DNA encapsulation by protamine. The DNA condensation by protamine was crucial for systemic in vivo gene transfer by CSVs. The PCSVs exhibited a higher gene expression in various organs, especially the liver, compared to DOTAP/Chol lipoplexes. These results demonstrate the potential for the use of PCSV as gene delivery vehicles for systemic gene transfer.

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Background In comparison with the general population, patients with Crohn’s disease (CD) are at higher risk of developing small bowel adenocarcinoma (SBA). However, with low prevalence of SBA, data regarding the impact of CD on survival are lacking. We investigated the impact of CD on survival in patients with SBA. Methods From January 1998 through July 2021, patients with histologically confirmed SBA were retrospectively collected and classified into binary, namely, sporadic SBA and CD-associated SBA groups. Patients with duodenal SBA were excluded. The overall survival (OS) and factors associated with survival were analysed. Results Of 127 patients with SBA, 115 patients were sporadic SBA and 12 were CD-associated SBA (Table 1). Compared to patients with sporadic SBA, poorly differentiated tumour was more common among patients with CD-associated SBA (41.7 vs. 14.8%, p=0.030). Other baseline demographic characteristics including age at the diagnosis of SBA, sex, Charlson morbidity score more than 2 points, smoking history, family history of cancer, location of SBA, initial stage based on American Joint Committee on Cancer (AJCC) staging system, and treatment showed no significant difference. In survival analyses, the 1-year (yr), 2-yr, and 5-yr OS were lower in patients with CD-associated SBA, without statistical significance (1-yr OS; 81.8 vs. 90.5%, 2-yr OS; 61.4 vs. 81.7, 5-yr OS; 61.4 vs. 69.1%, p=0.590) (Fig 1). Factors associated with decreased survival were disease stage (AJCC stage IV) (hazard ratio [HR] 5.485; 95% confidence interval [CI], 2.442–12.279, p<0.001) and palliative treatment (HR 2.447; 95% CI, 1.064–5.624, p=0.035), whereas curative operation plus adjuvant chemotherapy improved survival (HR 0.335; 95% CI, 0.132–0.849, p=0.021) (Table 2). Crohn’s disease was not significantly associated with survival (HR 1.333; 95% CI, 0.472–3.769, p=0.587). Conclusion The OS of patients with CD-associated SBA was not significantly lower than that of patients with sporadic SBA. The independent risk factors for survival were the stage of SBA and type of treatment, not Crohn’s disease.

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