EPI-X4, a CXCR4 antagonist inhibits tumor growth in pancreatic cancer and lymphoma models.

Endogenous peptide inhibitor for CXCR4 (EPI-X4) is a CXCR4 antagonist with potential for cancer therapy. It is a processed fragment of serum albumin from the hemofiltrate of dialysis patients. This study reports the efficacy of fifteen EPI-X4 derivatives in pancreatic cancer and lymphoma models. In vitro, the peptides were investigated for antiproliferation (cytotoxicity) by MTT assay. The mRNA expression for CXCR4 and CXCL12 was determined by RT-PCR, chip array and RNA sequencing. Chip array analysis yielded 634 genes associated with CXCR4/CXCL12 signaling. About 21% of these genes correlated with metastasis in the context of cell motility, proliferation, and survival. Expression levels of these genes were altered in pancreatic cancer (36%), lymphoma models (53%) and in patients' data (58%). EPI-X4 derivatives failed to inhibit cell proliferation due to low expression of CXCR4 in vitro, but inhibited tumor growth in the bioassays with significant efficacy. In the pancreatic cancer model, EPI-X4a, f and k inhibited mean tumor growth by > 50% and even caused complete remissions. In the lymphoma model, EPI-X4b, n and p inhibited mean tumor growth by > 70% and caused stable disease. Given the non-toxic and non-immunogenic properties of EPI-X4, these findings underscore its status as a promising therapy of pancreatic cancer and lymphoma and warrant further studies. SIMPLE SUMMARY: This study examined the value of chemokine receptor CXCR4 as an antineoplastic target for the endogenous peptide inhibitor of CXCR4 (EPI-X4), a 12-meric peptide derived from serum albumin. EPI-X4 inhibits CXCR4 interaction with its natural ligand, CXCL12 (SDF1). Therefore, malignancies (including pancreatic cancer and lymphoma) that depend on the CXCR4/CXCL12 pathway for progression can be targeted with EPI-X4. Of 634 genes that were linked to the CXCR4/CXCL12 pathway, 21% were associated with metastasis. In cultured human Suit2-007 pancreatic cancer cells, CXCR4 showed low to undetectable expression, which was why EPI-X4 did not inhibit pancreatic cancer cell proliferation. These findings were different in vivo, where CXCR4 was highly expressed and EPI-X4 inhibited tumor growth in rodents harboring pancreatic cancer or lymphoma. In the pancreatic cancer model, EPI-X4 derivatives a, f and k caused complete remissions, while in lymphomas EPI-X4 derivatives b, n and p caused stable disease.

COVID-19 Vaccinating Russian Medical Students-Challenges and Solutions: A Cross-Sectional Study.

Background: The role of preventive measures increases significantly in the absence of effective specific COVID-19 treatment. Mass population immunization and the achievement of collective immunity are of particular importance. The future development of public attitudes towards SARS-CoV-2 immunization depends significantly on medical students, as future physicians. Therefore, it seemed relevant to determine the percentage of COVID-19-vaccinated medical students and to identify the factors significantly affecting this indicator. Methods: A total of 2890 medical students from years one to six, studying at nine leading Russian medical universities, participated in an anonymous sociological survey. The study was performed in accordance with the STROBE guidelines. Results: It was found that the percentage of vaccinated Russian medical students at the beginning of the academic year 2021 was 58.8 ± 7.69%, which did not significantly differ from the vaccination coverage of the general population in the corresponding regions (54.19 ± 4.83%). Student vaccination rate was largely determined by the region-specific epidemiological situation. The level of student vaccination coverage did not depend on the gender or student residence (in a family or in a university dormitory). The group of senior students had a higher number of COVID-19 vaccine completers than the group of junior students. The lack of reliable information about COVID-19 vaccines had a pronounced negative impact on the SARS-CoV-2 immunization process. Significant information sources influencing student attitudes toward vaccination included medical professionals, medical universities, academic conferences, and manuscripts, which at that time provided the least information. Conclusion: The obtained results make it possible to develop recommendations to promote SARS-CoV-2 immunoprophylaxis among students and the general population and to increase collective immunity.