Coincidence of Sarcoidosis and a COVID-19 vaccine-associated hypermetabolic lymphadenopathy in a patient with a history of invasive breast cancer: A case report.

Introduction and importance: Vaccine-associated hypermetabolic lymphadenopathy (VAHL) after a COVID 19 vaccination is a common adverse event and also a diagnostic challenge especially in patients with a history of a malignancy. Case presentations: A 47-year-old woman presented with enlarged lymph nodes in the right hilar, subcarinal, and right supraclavicular regions detected by computed tomography as a postoperative follow-up study of thyroid cancer. Fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) performed 3 weeks later revealed an FDG uptake in those swollen lymph nodes and in the novel lymphadenopathy in the left axilla and left subclavicular regions. Both biopsy specimens from the right supraclavicular and hilar lymph nodes revealed only multiple small granulomas with multinucleated giant cells without malignancy, consistent with sarcoidosis. The left axilla and subclavicular lymphadenopathy detected by the FDG-PET subsequently spontaneously regressed. Clinical discussion: The coincidental occurrence of VAHL and lymphadenopathy in sarcoidosis patients could cause diagnostic confusion especially in those with breast cancer. Conclusion: Sufficient attention should be paid both to the injection site and the time interval between the vaccination and imaging test in the era of nationwide mass vaccinations against COVID 19.

Development of an orally-administrative MELK-targeting inhibitor that suppresses the growth of various types of human cancer.

We previously reported MELK (maternal embryonic leucine zipper kinase) as a novel therapeutic target for breast cancer. MELK was also reported to be highly upregulated in multiple types of human cancer. It was implied to play indispensable roles in cancer cell survival and indicated its involvement in the maintenance of tumor-initiating cells. We conducted a high-throughput screening of a compound library followed by structure-activity relationship studies, and successfully obtained a highly potent MELK inhibitor OTSSP167 with IC50 of 0.41 nM. OTSSP167 inhibited the phosphorylation of PSMA1 (proteasome subunit alpha type 1) and DBNL (drebrin-like), which we identified as novel MELK substrates and are important for stem-cell characteristics and invasiveness. The compound suppressed mammosphere formation of breast cancer cells and exhibited significant tumor growth suppression in xenograft studies using breast, lung, prostate, and pancreas cancer cell lines in mice by both intravenous and oral administration. This MELK inhibitor should be a promising compound possibly to suppress the growth of tumor-initiating cells and be applied for treatment of a wide range of human cancer.