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Objective:To investigate the effects of miRNA-30a-5p (miR-30a-5p) and metadherin (MTDH) on the proliferation, invasion and migration abilities of human breast cancer cells in vitro.Methods:The expression of MTDH in cancer and paracancerous tissues of 112 breast cancer patients in the database and miR-30a-5p in cancer and paracancerous tissues of 103 breast cancer patients in the database were analyzed using data from The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was used to analyze the correlation between miR-30a-5p and MTDH in 1 222 breast cancer patients in the database; the data were updated to August 2022. Breast cancer MDA-MB-231 cells were divided into negative control group (transfected with negative control sequence), miR-30a-5p overexpression group (transfected with miR-30a-5p mimics), siMTDH group [transfected with small interfering RNA against MTDH (siMTDH)], siMTDH+miR-30a-5p overexpression group (transfected with both siMTDH and miR-30a-5p mimics); cell proliferation ability was detected by methyl thiazol tetrazolium (MTT) assay, cell migration ability was detected by cell scratch assay, cell invasion ability was detected by Transwell assay. The relative expressions of miR-30a-5p, MTDH, matrix metalloproteinase (MMP)-2, MMP-9, vimentin and β-catenin mRNA in cells were detected by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR), and the expressions of MTDH, N-cadherin (N-cad), β-catenin, Snail and MMP-9 proteins were detected by Western blotting.Results:In the TCGA database, MTDH expression level was higher and miR-30a-5p expression level was lower in breast cancer tissues compared with paracancerous tissues, and the differences were statistically significant (both P < 0.001). There was a negative correlation between MTDH and miR-30a-5p expressions in 1 222 patients with breast cancer ( r=-0.134, P < 0.001). Compared with the negative control group, the cell proliferation ability was reduced in both siMTDH group and miR-30a-5p overexpression group at 24, 48 and 72 h (all P < 0.001). The cell scratch healing rate in miR-30a-5p overexpression group and siMTDH group was lower than that in negative control group [(61.6±1.6)%, (54.7±5.9)% vs. (80.3±3.0)%] (both P < 0.05). Compared with the negative control group, The number of migrated cells in miR-30a-5p overexpression group and siMTDH group was less than that in negative control group (881±50, 725±63 vs. 1 172±66) (both P < 0.05). Compared with the negative control group, the relative expressions of MMP-2, MMP-9, vimentin and β-catenin mRNA were all down-regulated in MDA-MB-231 cells of miR-30a-5p overexpression group and siMTDH group (all P < 0.05). Compared with the negative control group, the relative expressions of N-cad, β-catenin, Snail and MMP-9 proteins were down-regulated in MDA-MB-231 cells of miR-30a-5p overexpression group and siMTDH group (all P < 0.05). There was no statistical difference in the number of migrated MDA-MB-231 cells between siMTDH+miR-30a-5p overexpression group and siMTDH group (476±5 vs. 389±46, t = 3.37, P = 0.078). There was no statistical difference in the number of migrated cells between siMTDH+miR-30a-5p overexpression group and miR-30a-5p overexpression group (476±5 vs. 477±22, t = 0.02, P = 0.983). Conclusions:The expression of miR-30a-5p is negatively correlated with the expression of MTDH in breast cancer tissues, and either overexpression of miR-30a-5p or silence of MTDH in breast cancer MDA-MB-231 cells in vitro can inhibit cell proliferation, invasion and migration, but MTDH may not be a target gene of miR-30a-5p.
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Objective:To investigate the clinicopathological characteristics, gene mutation and prognosis of adenoid cystic carcinoma of the breast (AdCC).Methods:A total of 12 cases of AdCC samples archived at Linyi Cancer Hospital from January 2008 to December 2021 were collected, including 8 cases of classic adenoid cystic carcinoma (C-AdCC) and 4 cases of solid-basaloid adenoid cystic carcinoma (SB-AdCC). Histomorphology, immunohistochemicstry and molecular genetics were performed to analyze the clinicopathological characteristics and the prognosis of AdCC.Results:C-AdCC patients grew in the shape of beam-tubuler and cribriform architecture, with characteristic structures of true and pseudoadenoid lumen; SB-AdCC patients grew in nests and solid, with moderate to severe atypia, necrosis and high mitotic count. Immunohistochemistry showed that CK7, CK5/6, p63 and S-100 were expressed in 8 cases of C-AdCC, and CD117 and CD10 were diffusely expressed in 4 cases of SB-AdCC. Fluorescence in situ hybridization (FISH) showed that 3 C-AdCC patients had MYB gene break. Next-generation sequencing (NGS) revealed NOTCH1 gene mutation was detected in 2 SB-AdCC patients. No lymph node metastasis was observed in 8 patients with C-AdCC, but 2 had postoperative lymph node metastasis in 4 patients with SB-AdCC.Conclusions:C-AdCC mainly grows in beam-tubular and sieve shape, with low-grade atypia and good prognosis. Some cases have MYB-NFIB fusion gene. SB-AdCC mainly shows nest-mass, solid growth, moderate to severe atypia, necrosis and mitosis (>5/10 high power field) as well as poor prognosis; some patients have NOTCH1 gene mutation.
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Objective:To investigate the radiation dosimetry and biodistribution of 68Ga-FAPI-04 PET/CT in patients with hepatobiliary tumor. Methods:A total of six patients with hepatic lesions who underwent PET/CT examination in Peking Union Medical College Hospital were enrolled. After intravenous injection of radiotracer 68Ga-FAPI-04 at (170.57 ± 14.43) MBq, whole-body imaging were performed at the time points of 3, 10, 15, 20, 30 and 60 min, respectively. Biodistribution pattern was observed. Regions of interest were manually delineated. Radiation dosimetry of all target organs were calculated by Olinda/EXM software. Results:The radioactive uptake dissipated gradually in liver whereas it was relatively stable in tumor lesions. The average SUV max of tumor lesions reached the maximum value (13.87± 2.55) at 20 min after injection. The target-to-background ratio increased with time, reaching the maximum value (10.09 ± 8.17) at 30 min after injection. The average effective dose in total body was (0.020 ± 0.002) mSv/MBq and organ with the highest effective dose was bladder wall at (0.146 ± 0.035) mSv/MBq. Conclusions:The effective dose in total body of 68Ga-FAPI-04 was similar to that of 18F-FDG. 68Ga-FAPI-04 is expected to be a PET/CT radiotracer for hepatobiliary tumors in consideration of rapid tumor uptake, low accumulation of liver background, and no influence of blood sugar levels.
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Objective:To prepare 68Ga-fibroblast activation protein inhibitor (FAPI)-04, and evaluate its biodistribution and imaging characteristics in animals and healthy volunteers, in order to investigate the clinical translation potential. Methods:68Ga-FAPI-04 was synthesized by a manual method and its radiolabeling yield, radiochemical purity, and stability ( in vivo and in vitro) were analyzed. ICR mice ( n=16) were scarified at 5, 30, 60 and 120 min postinjection of 68Ga-FAPI-04 (1.11 MBq) to measure radioactive counts in main organs. The dynamic mircoPET imaging was acquired for 60 min on 3 ICR mice, and tumor imaging capabilities were examined with nude mice bearing HepG2 tumors. Furthermore, 2 healthy volunteers (1 male with age of 64 years, 1 female with age of 56 years) were recruited for the investigation of probe biodistribution in humans. A serial whole-body dynamic PET/CT scan was performed immediately following injection. Results:68Ga-FAPI-04 was synthesized within 20 min with the radiochemical yield of (68.7±4.0)% (decay corrected). The radiochemical purities of 68Ga-FAPI-04 were over 99% and the products were stable for 180 min in vitro and for 90 min in blood. 68Ga-FAPI-04 was mainly cleared through urinary tracts, while other organs only showed mild tracer accumulation. MicroPET imaging showed high uptake of 68Ga-FAPI-04 in the tumor tissue of mice, and the ratio of tumor/liver was 2.14±0.01 (35 min). The PET/CT imaging results of healthy volunteers revealed 68Ga-FAPI-04 could be quickly cleared. Conclusion:68Ga-FAPI-04 has many advantages for PET imaging, such as easy labeling, good stability, quick clearance and low background signals in the liver, which can be used as an attractive PET tracer for detection hepatocellular carcinoma.
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Objective To determine whether glucagon-like peptide-1 (GLP-1) receptor PET/CT with 68Ga-exendin-4 is accurate in localizing insulinomas, by comparing with conventional imaging techniques.Methods In this prospective cohort study, patients with biochemically proven endogenous hyperinsulinemic hypoglycemia from March 2014 to November 2016 were recruited consecutively.68Ga-exendin-4 PET/CT, CT, MRI, endoscopic ultrasound (EUS), and SSTR imaging were performed before elective surgery.Surgical pathology results were considered as the gold standard.Sensitivity based on patient-analysis and positive predictive value (PPV) based on lesion-analysis were calculated and compared using χ2 test and generalized score test.Results A total of 109 patients were recruited (47 males, 62 females;average age (45.1±14.8) years), and 96 of them with insulinomas proved pathologically were included in the main assessment.Thirteen patients with positive 68Ga-exendin-4 PET/CT findings did not undergo surgical intervention.Based on patient-analysis, the sensitivities of 68Ga-exendin-4 PET/CT, CT, MRI, EUS and SSTR imaging for detecting insulinomas were 98.96%(95/96), 81.25%(78/96), 79.41%(54/68), 81.40%(35/43) and 21.84%(19/87), respectively.Based on lesion-analysis, the PPV of the above 5 methods were 100%(102/102), 97.56%(80/82), 95.16%(59/62), 83.72%(36/43) and 90.48%(19/21), respectively.68Ga-exendin-4 PET/CT showed the highest diagnostic sensitivity than others (all P<0.01) and higher PPV than MRI, EUS and SSTR imaging (all P<0.05).Conclusion 68Ga-exendin-4 PET/CT is a highly sensitive imaging technique for detection of insulinoma.
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Objective To determine whether glucagon-like peptide-1 (GLP-1) receptor PET/CT with 68Ga-exendin-4 is accurate in localizing insulinomas,by comparing with conventional imaging techniques.Methods In this prospective cohort study,patients with biochemically proven endogenous hyperinsulinemic hypoglycemia from March 2014 to November 2016 were recruited consecutively.68Ga-exendiri-4 PET/CT,CT,MRI,endoscopic ultrasound (EUS),and SSTR imaging were performed before elective surgery.Surgical pathology results were considered as the gold standard.Sensitivity based on patient-analysis and positive predictive value (PPV) based on lesion-analysis were calculated and compared using x2 test and generalized score test.Results A total of 109 patients were recruited (47 males,62 females;average age (45.1±14.8) years),and 96 of them with insulinomas proved pathologically were included in the main assessment.Thirteen patients with positive 68Ga-exendin-4 PET/CT findings did not undergo surgical intervention.Based on patient-analysis,the sensitivities of 68Ga-exendin-4 PET/CT,CT,MRI,EUS and SSTR imaging for detecting insulinomas were 98.96％ (95/96),81.25％ (78/96),79.41％ (54/68),81.40％ (35/43) and 21.84％ (19/87),respectively.Based on lesion-analysis,the PPV of the above 5 methods were 100％ (102/102),97.56％ (80/82),95.16％ (59/62),83.72％ (36/43) and 90.48％ (19/21),respectively.68 Gaexendin-4 PET/CT showed the highest diagnostic sensitivity than others (all P＜0.01) and higher PPV than MRI,EUS and SSTR imaging (all P＜0.05).Conclusion 68Ga-exendin-4 PET/CT is a highly sensitive imaging technique for detection of insulinoma.