1.Fibroblast activation protein targeting radiopharmaceuticals: From drug design to clinical translation.
Yuxuan WU ; Xingkai WANG ; Xiaona SUN ; Xin GAO ; Siqi ZHANG ; Jieting SHEN ; Hao TIAN ; Xueyao CHEN ; Hongyi HUANG ; Shuo JIANG ; Boyang ZHANG ; Yingzi ZHANG ; Minzi LU ; Hailong ZHANG ; Zhicheng SUN ; Ruping LIU ; Hong ZHANG ; Ming-Rong ZHANG ; Kuan HU ; Rui WANG
Acta Pharmaceutica Sinica B 2025;15(9):4511-4542
The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.
2.A dual-targeting peptide-drug conjugate based on CXCR4 and FOLR1 inhibits triple-negative breast cancer.
Kun WANG ; Cong WANG ; Hange YANG ; Gong CHEN ; Ke WANG ; Peihong JI ; Xudong SUN ; Xuegong FAN ; Jie MA ; Zhencun CUI ; Xingkai WANG ; Hao TIAN ; Dengfu WU ; Lu WANG ; Zhimin WANG ; Jiangyan LIU ; Juan YI ; Kuan HU ; Hailong ZHANG ; Rui WANG
Acta Pharmaceutica Sinica B 2025;15(10):4995-5009
Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8+ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.
3.Progress of IL-21 and Tfh Mediated Immunotherapy in Non-small Cell Lung Cancer
LIU XINGKAI ; ZHANG YIFAN ; ZHANG XIN ; HE GONGHAO ; CAI WENKE
Chinese Journal of Lung Cancer 2024;27(7):550-558
Non-small cell lung cancer(NSCLC)is a prevalent and aggressive global malignancy.Conventional sur-gical treatments,radiotherapy,chemotherapy,and targeted therapies often fall short in halting disease progression due to inher-ent limitations,resulting in suboptimal prognosis.Despite the advent of immunotherapy drugs offering new hope for NSCLC treatment,current efficacy remains insufficient to meet all patient needs.Therefore,actively exploring novel immunotherapeu-tic approaches to further reduce mortality rates in NSCLC patients has become a crucial focus of NSCLC research.This article aims to systematically review the anti-tumor effects ofinterleukin-21 and follicular helper T cells in NSCLC immunotherapy by summarizing and analyzing relevant literatures from both domestic and international sources,as well as exploring the potential for enhancing NSCLC treatment prospects through immune checkpoint regulation via immunotherapeutic means.
4.Prediction of Bioequivalence of Lenvatinib Mesilate Capsules Based on Parallel Artificial Membrane Permeability Analysis
Hua ZHENG ; Guizhou HAO ; Pingping SHANG ; Jipeng HOU ; Qingxiao LIU ; Xingkai GENG ; Guimin ZHANG
Chinese Journal of Modern Applied Pharmacy 2024;41(13):1775-1780
OBJECTIVE
To predict the in vivo bioequivalence of lenvatinib mesilate capsules and reference preparation by using the parallel artificial membrane permeability analysis.
METHODS
Based on the biopharmaceutics classification system classification of lenvatinib mesilate and the parallel artificial membrane permeation model, the in vitro dissolution permeation rate test model of lenvatinib mesilate capsules was established, through real-time monitoring of the dissolution and penetration of lenvartinib mesylate capsules and reference preparations in fasting gastric juice, intestinal fluid and postprandial intestinal fluid, the flux and total penetration of drugs through the membrane were calculated.
RESULTS
In fasting state and fed state, the 90% confidence interval of geometric mean ratio of two key quality parameters (permeation flux and permeation amount) of the preparation A all were in the range of 80.00%−125.00%, the preparation B did not fall into this interval.
CONCLUSION
This research method can predict the bioequivalence of renvartinib mesylate capsule and reference preparation, and has a certain correlation in vivo and in vitro.
5.Real-world Study on the Efficacy,Safety and Economics of Vancomycin Hydrochloride for Injection from Two Manufacturers
Haixia ZHANG ; Xingkai CHEN ; Pei LIANG ; Jinchun LIU ; Yichen LI ; Mengying LIU ; Siliang WANG ; Huaijun ZHU ; Weihong GE
Herald of Medicine 2023;42(12):1850-1855
Objective To evaluate the differences in efficacy,safety and economics of vancomycin hydrochloride for injection between two manufacturers based on real-world data.Methods A total of 6 757 cases of intravenous use of vancomycin hydrochloride for injection from different manufacturers between January 1,2013 and December 31,2019 in the Affiliated Drum Tower Hospital of Nanjing University Medical School were retrospectively analyzed,and 5308 cases were matched by 1∶1 propensity score method,including 2 654 cases in the group A(domestic drug group)and 2 654 cases in group B(the innovator drug group).The differences in efficacy and safety between the two groups were compared.Cost-effectiveness analysis was used to compare the drug economics of the two groups.Results There were no significant differences in clinical cure rate,bacterial clearance rate,and incidence of adverse events between the two groups(P>0.05).In terms of economics,the average cost of vancomycin per capita,average daily cost of vancomycin and average cost of antibiotics per capita were significantly different between the two groups(P<0.05),and the cost of group B was higher than that of group A.Conclusion The efficacy and safety of vancomycin hydrochloride for injection were consistent between the two manufacturers.
6.Value of clinical staging and typing of hilar cholangiocarcinoma in evaluating radical resection and prognosis
Qi XIN ; Xiaoyuan YU ; Xingkai LIU
Journal of Clinical Hepatology 2020;36(2):472-475
Hilar cholangiocarcinoma (HCCA) is a malignant tumor arising from the epithelium of the bile duct, which involves the common hepatic duct, the left and right hepatic ducts, and the confluence areas of these bile ducts. HCCA has an insidious onset and most patients are in the advanced stage when jaundice is observed, and therefore it is considered a difficult issue in the field of surgery. Radical resection is the optimal method for the treatment of HCCA and has great influence on recurrence rate of tumor and patients’ survival time. Therefore, preoperative evaluation of tumor resectability is an important step of HCCA treatment. At present, there are eight main methods for HCCA staging and typing, i.e., Bismuth-Corlette classification system, modified T staging system, TNM staging system, JSBS staging system, Gazzaniga staging system, International Cholangiocarcinoma Group staging system, Mayo staging system, and Blechacz staging system. Each staging and typing system has its own advantages and disadvantages in clinical practice. This article reviews the staging and typing methods for HCCA, with a focus on the clinical value of each staging and typing system in preoperative evaluation of radical resection and prognosis.
7. Evaluation of different staging methods on radical resection rate and prognosis of patients with hilar cholangiocarcinoma
Qi XIN ; Xiaoyuan YU ; Xingkai LIU ; Ping ZHANG
Chinese Journal of Hepatobiliary Surgery 2019;25(11):828-833
Objective:
To compare the Bismuth-Corlette typing, modified T-staging and Mayo staging system in predicting the radical resection rates and prognosis of patients with hilar cholangiocarcinoma (HCC).
Methods:
The clinical data of 138 patients with hilar cholangiocarcinoma treated in the First Bethune Hospital of Jilin University were retrospectively analyzed. Three different staging methods were used.
Results:
With increase in the classification level of the Bismuth-Corlette classification, the radical resection rate did not significantly decrease (
8.Inhibition of proliferation and invasion of renal cancer cells by miR-125a-5p targeting STAT3 and its possible mechanism
YANG Ming ; JIANG Taimao ; LIU Xingkai ; YANG Zhiwei
Chinese Journal of Cancer Biotherapy 2019;26(11):1235-1242
Objective: To investigate the effects of miR-125a-5p targeting signal transducer and activator of transcription-3 (STAT3) on proliferation and invasion of renal cancer cells, and to preliminarily analyze the action mechanism. Methods: During the period from March 2017 to February 2018, 48 pairs of cancer tissues and corresponding normal adjacent tissues (more than 3 cm away from the tumor margin) resected from patients underwent renal cancer surgery at the Department of Urology, the Air Force Hospital of the Northern War Zone were collected for this study. Normal renal HK-2 cells and renal cancer cells (A498, GRC-1, 786-O and ACHN) were cultured in vitro. The expression of miR-125a-5p in above mentioned tissues and cells was detected by qPCR. miR-125a-5p-NC, miR-125a-5p-mimics, pLV-STAT3 and pLV-STAT3 with miR-125a-5p mimics were transfected intoA498 cells, namely NC group (negative control group), miR-125a-5p-mimics group, pLV-STAT3 group and pLV-STAT3+mimics group. The normally cultured A498 cells were used as blank control (Ctrl group). qPCR was performed to detect them RNA expressions of miR-125a-5p and STAT3 in cells of all groups. The bioinformatics prediction software and Dual luciferase assay were performed to analyze the targeting relationship between miR-125a-5p and STAT3. CCK-8, Flow cytometry, Transwell chamber assay were performed to detect cell proliferation activity, apoptosisand invasion, respectively. The expressions of STAT3, Bcl-2, BAX, cleaved cysteinyl aspartate specific proteinase 3 (cl-caspase-3), tumor suppressor gene p21, N-cadherin, E-cadherin, VEGF and HIF-1 in the cells were detected by WB. Results: The expression of miR-125a-5p in renal cancer tissues and cells was significantly lower than that in adjacent normal tissues and normal renal cells (all P<0.05). Compared with NC group, expression of miR-125a-5p in A498 cells transfected with miR-125a-5p-mimics was significantly increased, while expression of STAT3 mRNA was significantly decreased (all P<0.05). STAT3 was the target gene of miR-125a5p. Compared with NC group, cell viability, number of invasive cells, expressions of Bcl-2, N-cadherin, VEGF, HIF-1, and STAT3 as well as its phosphorylation level in miR-125a-5p mimics group were significantly decreased (all P<0.05), while cell apoptosis and expressions of BAX, p21, cl-caspase-3 and E-cadherin were significantly increased (all P<0.05); the cell viability, number of invasive cells, expressions of Bcl-2, N-cadherin, VEGF, HIF-1 and STAT3 as well as its phosphorylation level in pLV-STAT3 group were significantly increased (all P<0.05), while cell apoptosis and expressions of BAX, p21, cl-caspase-3 and E-cadherin were significantly decreased (all P<0.05). Compared with pLV-STAT3 group, cell viability, number of invasive cells, expressions of Bcl-2, N-cadherin, VEGF, HIF-1, and STAT3 as well asits phosphorylation level were significantly decreased in pLV-STAT3 mimics group (all P<0.05), while cell apoptosis, expressions of BAX, p21, cl-caspase-3 and E-cadherin were significantly increased (all P<0.05). Conclusion: miR125a-5p shows low expression in renal cancer tissues and cells, which can inhibit proliferation and invasion of A498 cells and promote cell apoptosis by down-regulating its target gene STAT3.
9. Research progress of lipolipomics in primary hepatocellular carcinoma
Xiaoju SHI ; Qianqian ZHENG ; Junqi NIU ; Guoyue LYU ; Xingkai LIU ; Guangyi WANG
Chinese Journal of Hepatology 2019;27(10):809-812
Presently, nonalcoholic fatty liver disease has become the most common pathogenic factor of chronic liver disease worldwide that can lead to the occurrence of hepatocellular carcinoma (HCC). Lipid metabolism in cancer cells is closely related to tumorgenesis, invasion and metastasis, and thus acts as one of the hallmark of cancer cells. Lipolipomics is an important branch of metabolomics, which has been adapted recently in the study of HCC for analysis of the structure and function of lipid components by chromatography and mass spectrometry. Fatty acids, glycerides, glycerophospholipids, sphingolipids, and sterol are significantly different in HCC tissues or serum. Therefore, it contributes to the diagnosis, determination of prognosis, mechanistic study and targeted therapy of HCC.
10. Control study of H-uvulopalatopharyngoplasty combined with tongue base radiofrequency for the treatment of obstructive sleep apnea hypopnea syndrome
Jianyong LIU ; Menglin LI ; Jianbin LU ; Yifang YUAN ; Xingkai MA ; Jingying YE
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2018;53(4):276-280
Objective:
To investigate the effect of H-uvulopalatopharyngoplasty(H-UPPP) combined with tongue base radiofrequency ablation in the treatment of obstructive sleep apnea hypopnea syndrome(OSAHS).
Methods:
Sixty-two patients with moderate or severe OSAHS, whose obstructive plane located in the oropharynx and tongue base were divided into two groups two groups according to the patient′s independent choice under the condition of fully informed before the operation. The control group of 30 cases underwent H-UPPP, while the experimental group of 32 patients underwent improved H-UPPP and tongue base radiofrequency. The clinical efficacy between the two groups was compared.
Results:
There was no significant difference between the two groups before operation. After the operation, the total effective rate of the experimental group was 71.9%, significantly higher than that of the control group (46.7%, χ2=4.09,


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