Tetsuya Kokabu

Glucose deprivation induces cisplatin resistance through upregulation of SLC7A11 (xCT) expression in endometrial cancer cells

Cisplatin resistance poses a substantial barrier to the successful treatment of advanced endometrial cancer. Glucose deprivation in the tumor microenvironment, resulting from inadequate vascularization and rapid proliferation of cancer cells, may promote chemoresistance by modifying cellular metabolism and survival pathways. This study aimed to elucidate how glucose deprivation induces cisplatin resistance in endometrial cancer cells, focusing on the role of solute carrier family 7 member 11 (SLC7A11, xCT). The endometrial cancer cell lines HEC-1A and AN3CA were cultured under glucose-deprived and glucose-supplemented conditions. Cisplatin half-maximal inhibitory concentration (IC50) values, SLC7A11 expression, and reactive oxygen species (ROS) levels were assessed using cell proliferation assays, real-time PCR, Western blotting, and fluorescence assays. SLC7A11 was inhibited using small interfering RNA (siRNA) knockdown and the selective inhibitor HG106. Cisplatin-resistant cell lines were generated to evaluate the effect of SLC7A11 inhibition. Glucose deprivation significantly decreased cisplatin sensitivity and increased cisplatin IC50 values (P < 0.05). This reduction in sensitivity was accompanied by upregulation of SLC7A11 expression and decreased ROS levels (P < 0.05). Inhibition of SLC7A11, either by siRNA or HG106, increased cisplatin sensitivity and ROS production, even in cisplatin-resistant cells (P < 0.05). This effect was reversible with the antioxidant N-acetylcysteine. These findings demonstrate that glucose deprivation induces cisplatin resistance in endometrial cancer cells by upregulating SLC7A11, leading to reduced ROS levels and enhanced cell survival. Targeting SLC7A11 restores cisplatin sensitivity by elevating ROS production, even in cisplatin-resistant cells. The findings suggest that SLC7A11 is a promising therapeutic target for overcoming chemoresistance in endometrial cancer, potentially improving treatment outcomes and patient survival.

Computed tomography, magnetic resonance imaging, and positron emission tomography/computed tomography findings for the diagnosis of malignant struma ovarii: A case report

AbstractMalignant struma ovarii (MSO) is an extremely rare disease arising from struma ovarii. Preoperative diagnosis is still challenging due to the lack of criteria for imaging findings. Herein, we report a case of MSO with suggestive imaging findings for a 50‐year‐old woman who presented with a pelvic tumor. The tumor did not typically show characteristic imaging findings of struma ovarii; however, the findings implied colloids of thyroid tissue within solid components on the magnetic resonance imaging (MRI) and computed tomography. Additionally, the solid components showed hyperintensity on diffusion‐weighted image and hypointensity on apparent diffusion coefficient maps. Total abdominal hysterectomy, bilateral salpingo‐oophorectomy, and omentectomy were performed. Histopathological examination revealed MSO of the right ovary, pT1aNXM0. The distribution of papillary thyroid carcinoma tissue corresponded to restricted diffusion area on MRI. In conclusion, the coexistence of imaging findings suggesting thyroid tissue and restricted diffusion in the solid component on MRI could indicate MSO.