An attractive strategy to overcome multidrug resistance in cancer chemotherapy is to suppress P-glycoprotein (P-gp), which is a pump overproduced in cancer cells to remove cytotoxic drugs from cells. In the present study, a Ca 2+ -permeable channel TRPC5 was found to be overproduced together with P-gp in adriamycin-resistant breast cancer cell line MCF-7/ADM. Suppressing TRPC5 activity/expression reduced the P-gp induction and caused a remarkable reversal of adriamycin resistance in MCF-7/ADM. In an athymic nude mouse model of adriamycin-resistant human breast tumor, suppressing TRPC5 decreased the growth of tumor xenografts. Nuclear factor of activated T cells isoform c3 (NFATc3) was the transcriptional factor that links the TRPC5 activity to P-gp production. Together, we demonstrated an essential role of TRPC5-NFATc3-P-gp signaling cascade in P-gp induction in drug-resistant cancer cells.

With comparable short-term and long-term effects on overall survival and tumor recurrence rate and with a shorter operative time, less blood loss, and a shorter hospital stay, RFA should be considered as the first choice for the treatment for very early HCCs as it presents an efficacious and economic option.

Background and AimThe relationship between subclinical hypothyroidism (SHYPO) and sleep quality is still unclear. Our objective was to compare the sleep quality between SHYPO patients and a control group with normal thyroid function.MethodsA total of 2224 patients with SHYPO and 12,622 euthyroid (EUTH) control group patients were included in the present study. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. The sleep outcomes were compared to explore the association between SHYPO and sleep quality. Furthermore, we tried to identify the risk factors of poor sleep in SHYPO patients.ResultsCompared to the EUTH control patients, SHYPO patients had a higher PSQI score (6.83 ± 2.67 vs 6.64 ± 2.63, p =0.004) and a higher proportion of poor sleepers (67.09% vs 64.75%, p =0.033). Moreover, subjects with SHYPO were associated with poorer sleep (Odd Ratio (OR) 1.120, 95% Confidence Intervals (CI) 1.016 to 1.235, p =0.023), longer sleep latency (OR 1.162, 95% CI 1.053 to 1.282, p =0.003), and shorter sleep duration (OR 1.148, 95% CI 1.019 to 1.293, p =0.023) after adjusting for potential confounders. Furthermore, we found that lower age, lower body mass index, and women were risk factors for poor sleep quality in SHYPO patients.ConclusionOur findings suggest a relationship between SHYPO and poor sleep quality in a large Chinese population.

Due to the higher postoperative morbidity and similar survival and tumor recurrence-free rates, LR might offer better or similar outcome over LT, but a larger number and further randomized studies may be needed in the future for drawing any positive conclusions.

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