Abstract. In order to improve our understanding of the potential preventive and therapeutic role of metformin, the present study aimed to investigate the capability of low-dose metformin in the efficient inhibition of cancer development and the reduction of the metastasis of endometrial adenocarcinoma type I and primary endometrial epithelial cells (eEPs), with the drug acting as a treatment in a hyperinsulinemic environment exposed to high and normal glucose conditions. The Ishikawa endometrial adenocarcinoma cell line and primary eEPs were exposed to an environment with high (17 mM) or normal glucose (5 mM) and treated with insulin, low-dose metformin (0.1 mM) or a combined treatment. Metastatic potential was assessed by migration and invasion assays, and relative cell proliferation was determined. Metformin at a low dose potently inhibited the insulin action, decreasing the ability of the endometrial cancer (EC) cell line to migrate and invade in a high and normal glucose environment, and decreasing the migration ability of the primary eEPs. In the EC cell line, the insulin treatment increased the proliferation, without any subsequent reduction of proliferation by the addition of 0.1 mM metformin; however, relative cell proliferation sensitivity to metformin was observed in the range between 1 and 5 mM regardless of the glucose concentration present. Overall, metformin at 0.1 mM is not efficient enough to decrease the proliferation in an EC cell line. However, at this concentration, metformin can inhibit the insulin action in endometrial epithelial cancer cells, demonstrating an anti-metastatic effect in high and normal glucose environments.

BACKGROUND: TB is commonly categorised as pulmonary (PTB) or extrapulmonary TB (EPTB). Knowledge of TB disease patterns (PTB and/or EPTB) and determining risk factors remains limited.METHODS: This was a prospective cohort study using point-of-care ultrasound (POCUS) in Indian patients with presumed TB. Clinical and imaging data were used to develop refined case definitions for PTB, concurrent PTB and EPTB (PTB + EPTB) and EPTB without PTB (EPTB). These groups were analysed by HIV (HIV+/–) and diabetes mellitus (DM+/–) status.RESULTS: Of 172 HIV–/DM– patients with TB, 48% had PTB, 23% PTB + EPTB and 29% had EPTB, totalling 52% with any EPTB (PTB + EPTB or EPTB). In HIV+/DM– patients with TB (n = 35), 6% had PTB, 40% had PTB + EPTB and 54% had EPTB, accounting for 94% with EPTB. In HIV–/DM+ patients with TB (n = 61), 61% had PTB, 28% had PTB + EPTB and 11% had EPTB, representing 39% with EPTB.CONCLUSION: Refined case definitions revealed high proportions of EPTB even without HIV or DM. HIV further altered the TB disease pattern towards EPTB and DM towards PTB. Therefore, the dichotomy between PTB or EPTB does not represent the actual spectrum of TB disease. EPTB should receive higher priority in research and clinical practice.