ABSTRACT
The thyroid gland is most frequently involved in immune-related adverse events (irAEs) by nivolumab. We reviewed the thyroid function and thyroid gland volume and volume change ratio between baseline and follow-up CT (volume follow-up/volume baseline) in 24 patients treated with nivolumab for lung cancer and renal cell carcinoma. Among them, four (16.7%) demonstrated nivolumab-induced thyroid dysfunction that shows either hypothyroidism or hyperthyroidism. Three and one cases were treated with nivolumab for lung cancer and renal cell carcinoma, respectively. Two patients with hypothyroidism (cases 1 and 2) showed reduced thyroid volume (volume change ratio: 0.80 and 0.84) on computed tomography (CT) images. Besides, remarkably diminished CT attenuation of the thyroid gland was observed in a patient with hypothyroidism (case 2). One of the two patients with hyperthyroidism showed increased thyroid volume (volume change ratio: 1.32) (case 3), whereas no difference in the thyroid gland volume was observed between the previous and follow-up CT in another patient with hyperthyroidism (case 4). Thyroid volume change ratio >0.1 was observed even in 6 of 20 (30%) patients without thyroid dysfunction. Considering the wide use of nivolumab in cancer treatment, radiologists should be aware that changes in the thyroid volume and attenuation on CT are associated with thyroid dysfunction caused by nivolumab, as well as thyroid volume may change even in patients with normal thyroid function during nivolumab therapy.
ABSTRACT
Sirtuin interacts with many regulatory proteins involved in energy homeostasis, DNA repair, cell survival, and lifespan extension. We investigated the functional roles of Sir2D during early Dictyostelium development upon starvation. We found that ectopic expression of Sir2D accelerated development among three Sirtuins containing highly homologous catalytic domain sequences to mouse Sirt1. Sir2D expression upregulated adenylate cyclase A (aca) mRNA expression 2, 4 and 6 h after starvation. We have previously reported that nicotinamide, a Sirt1 inhibitor, treatment delayed the development and decreased the expression of aca at 4 h after starvation. Sir2D expressing cells showed resistance against the nicotinamide effect. RNAi-mediated Sir2D knockdown cells were generated, and their development was also delayed. Aca expression was decreased 4 h after starvation. Sir2D expression restored the developmental impairment of Sir2D knockdown cells. The induction of aca upon starvation starts with transcriptional activation of MybB. The ectopic expression of MybB accelerated the development and increased the expression of aca 2 and 4 h after starvation but did not restore the phenotype of Sir2D knockdown cells. Sir2D expression had no effects on MybB-null mutant cells during early development. Thus, MybB is necessary for the upregulation of aca by Sir2D, and Sir2D is necessary for the full induction of aca after 4 h by MybB. MybB was coimmunoprecipitated with Sir2D, suggesting an interaction between MybB and Sir2D. These results suggest that Sir2D regulates aca expression through interaction with the MybB transcription factor early in Dictyostelium development upon starvation.
