Osteosarcoma is the most common primary malignant bone tumor. Although cisplatin is the primary chemotherapy used in osteosarcoma treatment, the cisplatin resistance remains a big challenge for improving overall survival. The store-operated calcium (Ca2+) entry (SOCE) and its major mediator Stim1 have been shown to be implicated in a number of pathological processes typical for cancer. In this study, we showed that Stim1 expression was significantly increased in chemo-resistant osteosarcoma tissues compared with chemo-sensitivity tissues. Patients with Sitm1 expression exhibited poorer overall survival than Stim1-negative patients. Moreover, un-regulation of Stim1 expression and SOCE were also observed in cisplatin-resistant MG63/CDDP cells compared with their parental cells. Cisplatin treatment obviously reduced Stim1 expression and SOCE in cisplatin-sensitivity MG63 cells, but had no effects on MG63/CDDP cells. In addition, cisplatin resulted in a more pronounced increase of endoplasmic reticulum (ER) stress in MG63 cells than in their resistant variants, which was evidenced by the activation of molecular markers of ER stress, GRP78, CHOP and ATF4. Knockdown of Stim1 using siRNA remarkably enhanced cisplatin-induced apoptosis and ER stress in MG63/CDDP cells, thereby sensitizing cancer cells to cisplatin. On the other hand, overexpression of Stim1 markedly reversed apoptosis and ER stress following cisplatin treatment. Taken together, these results demonstrate that Stim1 as well as Ca2+ entry contributes cisplatin resistance via inhibition of ER stress-mediated apoptosis, and provide important clues to the mechanisms involved in cisplatin resistance for osteosarcoma treatment. Stim1 represents as a target of cisplatin and blockade of Stim1-mediated Ca2+ entry may be a useful strategy to improve the efficacy of cisplatin to treat osteosarcoma.Electronic supplementary materialThe online version of this article (doi:10.1007/s13577-017-0167-9) contains supplementary material, which is available to authorized users.
The clinical applications of the quantitative single photon emission computed tomography (SPECT)/computed tomography (CT) are being expanded to a variety of fields of nuclear medicine. However, clinical application of quantitative SPECT/CT for the evaluation of Graves’ disease (GD) still needs further investigation. Our aim was to investigate the feasibility of standard uptake value (SUV) of the thyroid for the clinical diagnosis and evaluation of GD. In this prospective multicenter study, 116 patients diagnosed with GD (Graves group) and 74 healthy volunteers (control group) were enrolled from 8 different hospitals. All patients underwent technetium pertechnetate (TcO99m4-) SPECT/CT imaging with Q.Metrix quantitative software and 24-hour thyroid radioactive iodine uptake (24h-RAIU) test. The SUVmax and SUVmean in Graves group were significantly higher than those of control group (P<0.01). Cut-off values of SUVmax and SUVmean to predict GD were 231.425 and 116.66 by ROC curves, respectively. The SUVmax and SUVmean in Graves patients were significantly related to serum thyroxine level with correlation coefficient of 0.493 and 0.512 for FT3 and 0.449 and 0.464 for FT4, respectively (all P<0.01). Additionally, the SUVmax and SUVmean in GD positively correlated with 24h-RAIU with a coefficient of 0.832 and 0.830, respectively (P<0.01). The volumes determined by Q.Metrix (35.65 ± 20.56ml) of 72 subjects also positively correlated with that from ultrasound (36.67 ± 21.00ml) with a coefficient of 0.927 (P<0.01). SUV measurements derived from thyroid SPECT/CT may be useful for the clinical diagnosis and evaluation of GD.
A 50-year-old woman presented with a mass in the upper outer quadrant of her left breast, which proved to be a mucinous cystadenocarcinoma by biopsy. An 18F-FDG PET/CT was performed for staging, which showed that the breast tumor was the only lesion with abnormal 18F-FDG avidity. Breast-conserving surgery was performed following a negative sentinel lymph node biopsy of the left axilla, and primary mucinous cystadenocarcinoma of the breast was finally diagnosed.
A 74-year-old man with multiple soft tissue lesions in the lung, which were suspected to be metastatic neoplasms, underwent F-FDG PET/CT scan to detect primary malignancy. The images demonstrated that the lung and 2 retroperitoneal lymph nodes were the only affected organ or tissues with suspected primary lung neoplasms. Multiple intestinal-type adenocarcinoma was eventually diagnosed by CT-guided transthoracic needle aspiration biopsy.
A CT scan was performed on a 67-year-old man newly diagnosed with acute pancreatitis. The scan revealed a low-density lesion in the liver, a left renal nodule, and a right renal cystic mass. Intense F-FDG uptake was observed in the liver lesion and left renal nodule. No abnormal uptake was observed in the right renal mass. In addition, another focal intense uptake was observed in segment VII of the liver. Biopsies revealed intrahepatic cholangiocarcinomas in the 2 liver lesions, papillary renal cell carcinoma in the left renal lesion and clear cell renal cell carcinoma in the right renal lesion.
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