ABSTRACT
Post-acute sequelae of COVID-19 (PASC), also known as Long-Covid (LC), may affect 10-30 % of COVID-infected patients, and is characterized by a variety of debilitating symptoms lasting over 3 months after the acute infection, including but not limited to dyspnea, fatigue, and musculoskeletal, cognitive, and/or mental health impairments. Vitamin D is an essential nutrient primarily recognized for its role in regulating calcium and bone health but also endowed with potent anti-inflammatory activity affecting a variety of immune cells. We retrospectively evaluated the plasmatic levels of both 1,25-dihydroxyvitamin-D (1,25 OH), and 25-hydroxyvitamin-D (25 OH), the active and storage forms of vitamin-D3, respectively, in the serum of gynecologic cancer patients affected by PASC/LC vs control cancer patients. We found elevated 1,25-dihydroxyvitamin-D levels in 5 out of 5 of the PASC/LC patients (mean ± SD = 97.2 ± 26.9 pg/mL) versus 0 out of 10 of randomly selected cancer control patients (44.9 ± 17.2 pg/mL, p = 0.0005). In contrast, no significant difference was noted in the levels of 25-dihydroxyvitamin-D in PASC/LC (mean ± SD = 48.2 ± 15.8 ng/mL) versus controls (43.0 ± 11.6 ng/mL, p = 0.48). Importantly, abnormal levels of vitamin D were found to persist for at least 2 years in patients with long covid symptoms. The active form (1,25OH) but not the storage form (25 OH) of vitamin-D is significantly elevated in PASC/LC cancer patients. Abnormally and persistently elevated 1,25OH levels, similarly to sarcoidosis patients, may represent the results of extrarenal conversion of vitamin D by activated macrophages, and a novel biomarker of persistent inflammation in gynecologic cancer patients with PASC/LC.
ABSTRACT
OBJECTIVE: To compare the in vitro sensitivity/resistance to patupilone versus paclitaxel in uterine serous papillary carcinoma (USPC) with high versus low HER-2/neu expression. METHODS: Six primary USPC cell lines, half of which overexpress HER-2/neu at a 3+ level, were evaluated for growth rate and tested for their in vitro sensitivity/resistance to patupilone versus paclitaxel by MTS assays. Quantitative RT-PCR was used to identify potential mechanisms underlying the differential sensitivity/resistance to patupilone versus paclitaxel in primary USPC cell lines. RESULTS: Cell lines overexpressing HER-2/neu showed higher proliferation when compared to low HER-2/neu-expressing cell lines. Compared to low-expressing cell lines, high HER-2/neu expressors were significantly more sensitive to patupilone than to paclitaxel (P<0.0002). In contrast, there was no appreciable difference in sensitivity to patupilone versus paclitaxel in primary USPC cell lines with low HER-2/neu expression. Higher levels of ß-tubulin III (TUBB3) and P-glycoprotein (ABCB1) were detected in USPC cell lines with high versus low HER-2/neu expression (P<0.05). CONCLUSIONS: USPC overexpressing HER-2/neu display greater in vitro sensitivity to patupilone and higher levels of the patupilone molecular target TUBB3 when compared to low HER-2/neu expressors. Due to the adverse prognosis associated with HER-2/neu overexpression in USPC patients, patupilone may represent a promising novel drug to combine to platinum compounds in this subset of aggressive endometrial tumors.
