ABSTRACT
Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-89(89Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[89Zr]Zr-des-ferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,＞99％)and specific activity(24.15±1.34 GBq/μmol),and was stable in 5％human serum albumin,and phosphate buffer saline(＞85％RCP at 96 h).The EC50 values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P＞0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2(-).The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16％ID/g)than BGC823 mice(0.69±0.02％ID/g)and blocking group(0.72±0.02％ID/g).A dosimetry estimation study showed that the effective dose of[89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these re-sults suggest that Good Manufacturing Practices produced by this immuno-positron emission tomog-raphy probe can detect CLDN18.2-overexpressing tumors.
ABSTRACT
Objective:To assess the performance of Al 18F-prostate specific membrane antigen (PSMA)-BCH PET/CT in the detection and localization of early recurrent prostate cancer after radical prostatectomy. Methods:From July 2021 to July 2022, a cohort of 51 patients (age: 49-80(64.8±6.9) years) who underwent Al 18F-PSMA-BCH for biochemical recurrence with the prostate specific antigen (PSA) level less than 2 μg/L in Peking University Cancer Hospital & Institute were retrospectively analyzed. The patients were stratified into 4 groups (PSA<0.2 μg/L, 0.2 μg/L≤PSA<0.5 μg/L, 0.5 μg/L≤PSA<1 μg/L, 1 μg/L≤PSA<2 μg/L groups) according to different PSA levels. Lesions detected by Al 18F-PSMA-BCH PET/CT were recorded as prostate bed (including bed of seminal vesicles); pelvic, paraaortic, mediastinal/supraclavicular and axillary lymph nodes; bone lesions and visceral lesions. The detection rates among different groups were compared by Fisher exact test. Results:Of 51 patients, 30(58.8%) had evidence of abnormal uptake suggestive of recurrent prostate cancer, with 60.0%(18/30) had disease confined to the pelvis, including 26.7%(8/30) had prostate bed recurrence, 26.7%(8/30) had pelvic lymph nodes, 6.6%(2/30) had prostate bed recurrence with pelvic lymph nodes, while 40.0%(12/30) had extra pelvic disease. The detection rates of Al 18F-PSMA-BCH PET/CT in PSA<0.2 μg/L, 0.2 μg/L≤PSA<0.5 μg/L, 0.5 μg/L≤PSA<1 μg/L and 1 μg/L≤PSA<2 μg/L groups were 39.1%(9/23), 6/11, 8/9 and 7/8, respectively. There were no significant differences of detection rates between PSA<0.2 μg/L group and 0.2 μg/L≤PSA<0.5 μg/L group ( P=0.397) and also between 0.5 μg/L≤PSA<1 μg/L group and 1 μg/L≤PSA<2 μg/L group ( P=0.929). Conclusion:Al 18F-PSMA-BCH has a high detection rate for early recurrent prostate cancer, even at low PSA levels less than 0.2 μg/L.
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OBJECTIVE：To study the effect of Cangfu daotan pill （CDP）containing serum on autophagy of ovarian granulosa cells（GCs）of rat. METHODS ：Three-month-old SD rat were divided into normal saline group （normal saline ，ig），FSH injection group（10.71 IU/kg，ih），CDP irrigation high-dose ，medium-dose and low-dse groups [ 0.5，1，2 mg/g（by crude drug ），ig]，with 6 rats in each group. They were given relevant medicine subcutaneously/intragastrically ，once a day ，for consecutive 3 days. After last medication ，blood sample was collected from the abdominal aorta to obtain drug-containing serum. GCs of rat were divided into blank control group ，model group ，FSH group （positive control ）and CDP high-dose ，medium-dose and low-dose groups. The autophagy model was induced by giving testosterone propionate ，except that the blank control group was directly added with 100 μL serum of normal saline group. Then model group was given 100 μL serum of normal saline group，and administration groups were given 100 μL drug-containing serum of corresponding drug group. The contents of estradiol（E2）and progesterone （P）in supernatant of cells were determined by ELISA. Western blot assay was used to detect protein expression of PI 3K，Akt and mTOR in cells. The mRNA expression of PI 3K，Akt，mTOR，Beclin 1，LC3Ⅰ，LC3Ⅱ and p 62 were detected by RT-PCR. RESULTS ： Compared with blank control group ，the content of E 2 in supernatant ，relative mRNA and protein expression of PI 3K，Akt and mTOR were decreased significantly in model group （P＜0.01），while relative mRNA expression of Beclin 1，LC3Ⅰ and LC 3Ⅱ were increased significantly （P＜0.01）. Compared with model group ，the content of E 2 in supernatant were significantly increased in FSH group ，CDP medium-dose and high-dose groups ，while relative mRNA expression of Beclin 1，LC3Ⅰ，LC3Ⅱ and p 62 were decreased significantly （P＜0.05 or P＜0.01）；relative mRNA and protein expression of PI 3K，Akt and mTOR were increased significantly in administration groups （P＜0.05 or P＜0.01）. CONCLUSIONS ：CDP can inhibit autophagy of GCs by activating related protein and mRNA expression of PI 3K/Akt/ mTOR signaling pathway.
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OBJECTIVE：To study the effects of berberine on mic e macrophage polarization based on TLR 4-MyD88-NF-κB signaling pathway. METHODS ：Using mice RAW 264.7 macrophage as the object ，atorvastatin calcium as positive control ， inflammatory cell model was induced by lipopolysaccharide （LPS）；ELISA method was used to detect the contents of TNF-α，IL-6 and NF-κB in cell culture medium after treated with low，medium and high doses of berberine （5，10，20 μmol/L）for 24 h. The real-time fluorescence quantitative PCR was conducted to determine the mRNA expression of TLR 4 and MyD 88 in cells. Western blotting assay was used to detect the protein expression of TLR 4，MyD88，iNOS and CD 206 in cells. RESULTS ：Compared with blank control group ，the contents of TNF-α，IL-6 and NF-κB in cell culture medium，mRNA expression of TLR 4 and MyD 88， protein expression of TLR 4，MyD88 and iNOS in cells were increased significantly in LPS induction group （P＜0.05）. Compared with LPS induction group ，the contents of TNF-α and IL-6，mRNA and protein expression of TLR 4 and MyD 88 in atorvastatin calcium group ，berberine medium-dose and high-dose groupsas well as the content of NF-κ B and protein expression of iNOS in administration groups were decreased significantly ， while the content of NF-κB in berberine high-dose group was significantly lower than atorvastatin calcium group （P＜0.05）. The protein expressions of CD206 in atorvastatin calcium group and berberine high-dose group were increased significantly ，while the protein expression of CD 206 in berberine high-dose group was significantly higher than atorvastatin calcium group （P＜0.05）. CONCLUSIONS ：Different doses of berberine can intervene in mice macrophage polarization to different extents ，the mechanism of which may be associated with the regulation of TLR4/MyD88/NF-κB signaling pathway.
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OBJECTIVE： To systematically evaluate the difference in therapeutic efficacy， safety and cardiac function of Chinese patent medicine injection for promoting blood circulation and removing blood stasis combined with routine treatment after percutaneous coronary intervention （PCI）， and to provide evidence-based reference for clinical drug use. METHODS： Retrieved from Cochrane library， PubMed， Embase， CNKI， Wanfang database and Chinese sci-tech periodicals database， RCTs about different Chinese patent medicine injection for promoting blood circulation and removing blood stasis combined with routine treatment （trial group） versus routine treatment （control group） after PCI were collected. After screening the literature and extracting the data， the quality of the included studies was evaluated by modified Jadad scale. Bayesian network Meta- analysis was performed by using Stata 14.0 software and Markov Chain-Monte Carlo method. RESULTS： A total of 15 RCTs involving 1 364 patients were included， involving Salvia miltiorrhiza injection， Puerarin injection， Yiqi fumai injection， Xuebijing injection， Shenfu injection， Shuxuetong injection， Salvia miltiorrhiza and ligustrazine injection， Rhodiola wallichiana injection， Danhong injection. Results of Meta-analysis showed that in the aspect of improving total response rate of ECG， 8 kinds of intervention measures were involved；compared with control group， 7 kinds of intervention measures could improve the total response rate of ECG of trial group except for Shenfu injection （P＞0.05）； network Meta-analysis ranking showed that S. miltiorrhiza injection＞Puerarin injection＞Shenfu injection＞S. miltiorrhiza and ligustrazine injection＞Shuxuetong injection＞R. wallichiana injection＞ Danhong injection＞routine treatment. In terms of reducing adverse cardiovascular events （MACE） incidence，8 kinds of intervention measures were involved； compared with control group， 7 kinds of intervention measures could reduce the MACE incidence of trial group except for Puerarin injection （P＞0.05）； network Meta-analysis ranking showed that S. miltiorrhiza and ligustrazine injection＞Danhong injection＞Xuebijing injection＞Shuxuetong injection＞S. miltiorrhiza injection＞R. wallichiana injection＞ Puerarin injection＞routine treatment. In terms of improving left ventricular ejection fraction （LVEF） after treatment， 8 kinds of intervention measures were involved； compared with control group， 7 intervention measures could significantly improve LVEF after treatment of trial group except for R. wallichiana injection (P＞0.05）； network Meta-analysis ranking showed that S. miltiorrhiza and ligustrazine injection＞Yiqi fumai injection＞Danhong injection＞Shenfu injection＞S. miltiorrhiza injection＞Shuxuetong injection＞R. wallichiana injection＞routine treatment. CONCLUSIONS： Compared with routine treatment， S. miltiorrhiza injection is the best in improving total response rate of ECG； S. miltiorrhiza and ligustrazine injection is the best in reducing MACE incidence and improving LVEF after treatment.