Search

The COVID-19 pandemic has led to significant global health and economic consequences. There is an unmet need to define a molecular fingerprint of severity of the disease that may guide an early, rational and directed intervention preventing severe illness. We collected plasma from patients with moderate (nine cases), severe (22 cases) and critical (five cases) COVID-19 within three days of hospitalization (approximately one week after symptom onset) and used a cytokine antibody array to screen the 105 cytokines included in the array. We found that I-TAC, IP-10, ST2 and IL-1ra were significantly upregulated in patients with critical disease as compared to the non-critical (moderate and severe combined). ELISA further quantified I-TAC levels as 590.24±410.89, 645.35±517.59 and 1613.53±1010.59 pg/ml in moderate, severe and critical groups, respectively. Statistical analysis showed that I-TAC levels were significantly higher in patients with critical disease when compared with moderate (p = 0.04), severe (p = 0.03) or the combined non-critical (p = 0.02) group. Although limited by the low sample numbers, this study may suggest a role of I-TAC as a potential early marker to discriminate between critical and non-critical COVID-19 cases. Such knowledge is urgently needed for appropriate allocation of resources and to serve as a platform for future research towards early interventions that could mitigate disease severity and save lives.

Uterine carcinosarcoma (UCS) is a relatively infrequent, but extremely aggressive endometrial malignancy. Although surgery and chemotherapy have improved outcomes, overall survival (OS) remains dismal due to the lack of targeted therapy and biphasic (epithelial and mesenchymal) nature that renders the tumor aggressive and difficult to manage. Here we report a role of transforming growth factor-β (TGFβ) in maintaining epithelial to mesenchymal transition (EMT) phenotype and aggressiveness in UCS. Using a 3D-culture system, we evaluated the efficacy of the transforming growth factor-β receptor-I (TGFβR1) kinase inhibitor Galunisertib (GLT), alone and in combination with standard chemotherapeutic drugs used for the management of UCS. We demonstrate that GLT by inhibiting canonical and non-canonical signaling emanating from transforming growth factor-β1 (TGFβ1) reduces cellular viability, invasion, clonal growth and differentiation. Interestingly, GLT sensitizes UCS cells to chemotherapy both in vitro and in in vivo preclinical tumor model. Hence, targeting TGFβ signaling, in combination with standard chemotherapy, may be exploited as an important strategy to manage the clinically challenging UCS.