المؤلفون: Huaqing Wang, Jifeng Feng, Yanyan Liu, Zhengzi Qian, Da Gao, Xuehong Ran, Hui Zhou, Lihong Liu, Binghua Wang, Meiyun Fang, Hebing Zhou, Zhenqian Huang, Shi Tao, Zhuowen Chen, Liping Su, Hang Su, Yu Yang, Xiaobao Xie, Huijing Wu, Ping Sun, Guoyu Hu, Aibin Liang, Zhiming Li

المصدر: Signal Transduction and Targeted Therapy, Vol 9, Iss 1, Pp 1-9 (2024)

مصطلحات موضوعية: Medicine, Biology (General), QH301-705.5

الوصف: Abstract This registration study assessed clinical outcomes of TQ-B3525, the dual phosphatidylinositol-3-kinase (PI3K) α/δ inhibitor, in relapsed and/or refractory follicular lymphoma (R/R FL). This phase II study (ClinicalTrials.gov NCT04324879. Registered March 27, 2020) comprised run-in stage and stage 2. R/R FL patients after ≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Based on results (ORR, 88.0%; duration of response [DOR], 11.8 months; progression-free survival [PFS], 12.0 months) in 25 patients at run-in stage, second stage study was initiated and included 82 patients for efficacy/safety analysis. Patients received prior-line (median, 3) therapies, with 56.1% refractory to previous last therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6% (71/82; 95% CI, 77.3–93.1%), with 28 (34.2%) complete responses. Disease control rate was 95.1% due to 7 (8.5%) stable diseases. Median time to response was 1.8 months. Among 71 responders, median DOR was not reached; 18-month DOR rate was 51.6%. with median follow-up of 13.3 months, median PFS was 18.5 (95% CI, 10.2-not estimable) months. Median overall survival (OS) was not reached by cutoff date; 24-month OS rate was estimated as 86.1%. Response rates and survival data were consistent across all subgroups. Grade 3 or higher treatment-related adverse events were observed in 63 (76.8%) cases, with neutropenia (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. TQ-B3525 showed favorable efficacy and safety for R/R FL patients after ≥2 lines prior therapies.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2059-3635Test

الوصول الحر: https://doaj.org/article/b34bb7a2f1604af6b6438be5bc6ad089Test

المؤلفون: Jin Zhao, Meijing Zheng, Li Ma, Tao Guan, Liping Su

المصدر: Heliyon, Vol 10, Iss 9, Pp e29997- (2024)

مصطلحات موضوعية: Multiple myeloma (MM), Chimeric antigen receptor (CAR), CAR T-cell therapy (CAR-T), On-target/off-tumor (OTOT), Science (General), Q1-390, Social sciences (General), H1-99

الوصف: Multiple myeloma (MM), marked by abnormal proliferation of plasma cells and production of monoclonal immunoglobulin heavy or light chains in the majority of patients, has traditionally been associated with poor survival, despite improvements achieved in median survival in all age groups since the introduction of novel agents. Survival has significantly improved with the development of new drugs and new treatment options, such as chimeric antigen receptor T-cell therapy (CAR-T), which have shown promise and given new hope in MM therapy. CARs are now classified as first-, second-, and third-generation CARs based on the number of monovalent to trivalent co-stimulatory molecules incorporated into their design. The scope of this review was relatively narrow because it was mainly about a comparison of the literature on the clinical application of CAR-T therapy in MM. Thus, our goal is to provide an overview of the new advances of CAR-T cells in the cure of MM, so in this review we looked at the progress of the clinical use of CAR-T cells in MM to try to provide a reference for their clinical use when managing MM.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2405844024060286Test; https://doaj.org/toc/2405-8440Test

الوصول الحر: https://doaj.org/article/917f27178de145a2ab9d8a8b31f1739aTest

المؤلفون: Bingli Liu, Liping Su, Sze Jie Loo, Yu Gao, Ester Khin, Xiaocen Kong, Rinkoo Dalan, Xiaofei Su, Kok-Onn Lee, Jianhua Ma, Lei Ye

المصدر: Frontiers in Endocrinology, Vol 15 (2024)

مصطلحات موضوعية: atherosclerosis, type 2 diabetes, matrix metallopeptidase 9, inflammation, ischemic heart disease, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: AimsTo determine the roles of matrix metallopeptidase-9 (MMP9) on human coronary artery smooth muscle cells (HCASMCs) in vitro, early beginning of atherosclerosis in vivo in diabetic mice, and drug naïve patients with diabetes.MethodsActive human MMP9 (act-hMMP9) was added to HCASMCs and the expressions of MCP-1, ICAM-1, and VCAM-1 were measured. Act-hMMP9 (n=16) or placebo (n=15) was administered to diabetic KK.Cg-Ay/J (KK) mice. Carotid artery inflammation and atherosclerosis measurements were made at 2 and 10 weeks after treatment. An observational study of newly diagnosed drug naïve patients with type 2 diabetes mellitus (T2DM n=234) and healthy matched controls (n=41) was performed and patients had ultrasound of carotid arteries and some had coronary computed tomography angiogram for the assessment of atherosclerosis. Serum MMP9 was measured and its correlation with carotid artery or coronary artery plaques was determined.ResultsIn vitro, act-hMMP9 increased gene and protein expressions of MCP-1, ICAM-1, VCAM-1, and enhanced macrophage adhesion. Exogenous act-hMMP9 increased inflammation and initiated atherosclerosis in KK mice at 2 and 10 weeks: increased vessel wall thickness, lipid accumulation, and Galectin-3+ macrophage infiltration into the carotid arteries. In newly diagnosed T2DM patients, serum MMP9 correlated with carotid artery plaque size with a possible threshold cutoff point. In addition, serum MMP9 correlated with number of mixed plaques and grade of lumen stenosis in coronary arteries of patients with drug naïve T2DM.ConclusionMMP9 may contribute to the initiation of atherosclerosis and may be a potential biomarker for the early identification of atherosclerosis in patients with diabetes.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT04424706.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fendo.2024.1369369/fullTest; https://doaj.org/toc/1664-2392Test

الوصول الحر: https://doaj.org/article/d115bde3a15244e29582af6f5029243eTest

المؤلفون: Fangyuan Li, Junxian Yu, Tao Pan, Haoran Feng, Jianfang Li, Beiqin Yu, Zhiyuan Fan, Qingqing Sang, Mengdi Chen, Mingde Zang, Junyi Hou, Xiongyan Wu, Yingyan Yu, Yuan‐Yuan Li, Chao Yan, Zhenggang Zhu, Liping Su, Bingya Liu

المصدر: Advanced Science, Vol 10, Iss 34, Pp n/a-n/a (2023)

مصطلحات موضوعية: AU‐1, BPTF, EGFR‐TKI, erlotinib, gastric cancer, targeted therapy, Science

الوصف: Abstract Erlotinib, an EGFR tyrosine kinase inhibitor, is used for treating patients with cancer exhibiting EGFR overexpression or mutation. However, the response rate of erlotinib is low among patients with gastric cancer (GC). The findings of this study illustrated that the overexpression of bromodomain PHD finger transcription factor (BPTF) is partially responsible for erlotinib resistance in GC, and the combination of the BPTF inhibitor AU‐1 with erlotinib synergistically inhibited tumor growth both in vivo and in vitro. AU‐1 inhibited the epigenetic function of BPTF and decreased the transcriptional activity of c‐MYC on PLCG1 by attenuating chromosome accessibility of the PLCG1 promoter region, thus decreasing the expression of p‐PLCG1 and p‐Erk and eventually improving the sensitivity of GC cells to erlotinib. In patient‐derived xenograft (PDX) models, AU‐1 monotherapy exhibited remarkable tumor‐inhibiting activity and is synergistic anti‐tumor effects when combined with erlotinib. Altogether, the findings illustrate that BPTF affects the responsiveness of GC to erlotinib by epigenetically regulating the c‐MYC/PLCG1/pErk axis, and the combination of BPTF inhibitors and erlotinib is a viable therapeutic approach for GC.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2198-3844Test

الوصول الحر: https://doaj.org/article/a52d13ec381e41e3b9daef4653ccf9a8Test

المؤلفون: Lizhong Yao, Junyi Hou, Xiongyan Wu, Yifan Lu, Zhijian Jin, Zhenjia Yu, Beiqin Yu, Jianfang Li, Zhongyin Yang, Chen Li, Min Yan, Zhenggang Zhu, Bingya Liu, Chao Yan, Liping Su

المصدر: Redox Biology, Vol 67, Iss , Pp 102923- (2023)

مصطلحات موضوعية: Cancer-associated fibroblasts, NK cells, Iron regulation, Ferroptosis, Ferritinophagy, Medicine (General), R5-920, Biology (General), QH301-705.5

الوصف: As the predominant immunosuppressive component within the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) inhibit Natural Killer cell (NK cell) activity to promote tumor progression and immune escape; however, the mechanisms of cross-talk between CAFs and NK cells in gastric cancer (GC) remain poorly understood. In this study, we demonstrate that NK cell levels are inversely correlated with CAFs abundance in human GC. CAFs impair the anti-tumor capacity of NK cells by inducing ferroptosis, a cell death process characterized by the accumulation of iron-dependent lipid peroxides. CAFs induce ferroptosis in NK cells by promoting iron overload; conversely, decreased intracellular iron levels protect NK cells against CAF-induced ferroptosis. Mechanistically, CAFs increase the labile iron pool within NK cells via iron export into the TME, which is mediated by the upregulated expression of iron regulatory genes ferroportin1 and hephaestin in CAFs. Moreover, CAF-derived follistatin like protein 1(FSTL1) upregulates NCOA4 expression in NK cells via the DIP2A-P38 pathway, and NCOA4-mediated ferritinophagy is required for CAF-induced NK cell ferroptosis. In a human patient-derived organoid model, functional targeting of CAFs using a combination of deferoxamine and FSTL1-neutralizing antibody significantly alleviate CAF-induced NK cell ferroptosis and boost the cytotoxicity of NK cells against GC. This study demonstrates a novel mechanism of suppression of NK cell activity by CAFs in the TME and presents a potential therapeutic approach to augment the immune response against GC mediated by NK cells.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2213231723003245Test; https://doaj.org/toc/2213-2317Test

الوصول الحر: https://doaj.org/article/1a8ad35e533843c1aa456774f9853db2Test

المؤلفون: Tingting Zhang, Weiwei Tian, Shuang Wei, Xinyi Lu, Jing An, Shaolong He, Jie Zhao, Zhilin Gao, Li Li, Ke Lian, Qiang Zhou, Huilai Zhang, Liang Wang, Liping Su, Huicong Kang, Ting Niu, Ailin Zhao, Jing Pan, Qingqing Cai, Zhenshu Xu, Wenming Chen, Hongmei Jing, Peng Li, Wanhong Zhao, Yang Cao, Jianqing Mi, Tao Chen, Yuan Chen, Ping Zou, Veronika Lukacs-Kornek, Christian Kurts, Jian Li, Xiansheng Liu, Qi Mei, Yicheng Zhang, Jia Wei

المصدر: Experimental Hematology & Oncology, Vol 12, Iss 1, Pp 1-17 (2023)

مصطلحات موضوعية: SARS-CoV-2, COVID-19, CAR T-cell, Hematological malignancies, Treatment, Recommendations, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract The outbreak of coronavirus disease 2019 (COVID-19) posed an unprecedented challenge on public health systems. Despite the measures put in place to contain it, COVID-19 is likely to continue experiencing sporadic outbreaks for some time, and individuals will remain susceptible to recurrent infections. Chimeric antigen receptor (CAR)-T recipients are characterized by durable B-cell aplasia, hypogammaglobulinemia and loss of T-cell diversity, which lead to an increased proportion of severe/critical cases and a high mortality rate after COVID-19 infection. Thus, treatment decisions have become much more complex and require greater caution when considering CAR T-cell immunotherapy. Hence, we reviewed the current understanding of COVID-19 and reported clinical experience in the management of COVID-19 and CAR-T therapy. After a panel discussion, we proposed a rational procedure pertaining to CAR-T recipients with the aim of maximizing the benefit of CAR-T therapy in the post COVID-19 pandemic era.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2162-3619Test

الوصول الحر: https://doaj.org/article/317083c379354394bdbd8c7877d9e996Test

المؤلفون: Wenjie Guo, Yang Liu, Liping Su, Shanshan Guo, Fanfan Xie, Xiaoying Ji, Kaixiang Zhou, Xu Guo, Xiwen Gu, Jinliang Xing

المصدر: Molecular Oncology, Vol 17, Iss 5, Pp 857-871 (2023)

مصطلحات موضوعية: machine learning, mitochondrial DNA, next‐generation sequencing, somatic mutations, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Mitochondrial DNA (mtDNA) somatic mutations play important roles in the initiation and progression of cancer. Although next‐generation sequencing (NGS) of paired tumor and control samples has become a common practice to identify tumor‐specific mtDNA mutations, the unique nature of mtDNA and NGS‐associated sequencing bias could cause false‐positive/‐negative somatic mutation calling. Additionally, there are clinical scenarios where matched control tissues are unavailable for comparison. Therefore, a novel approach for accurately identifying somatic mtDNA variants is greatly needed, particularly in the absence of matched controls. In this study, the ground truth mtDNA variants orthogonally validated by triple‐paired tumor, adjacent nontumor, and blood samples were used to develop mitoSomatic, a random forest‐based machine learning tool. We demonstrated that mitoSomatic achieved area under the curve (AUC) values over 0.99 for identifying somatic mtDNA variants without paired control in three tumor types. In addition, mitoSomatic was also applicable in nontumor tissues such as adjacent nontumor and blood samples, suggesting the flexibility of mitoSomatic's classification capability. Furthermore, analysis of triple‐paired samples identified a small group of variants with uncertain somatic/germline origin, whereas application of mitoSomatic significantly facilitated the prediction of their possible source. Finally, a control‐free evaluation of the public pan‐cancer NGS dataset with mitoSomatic revealed a substantial number of variants that were probably misclassified by conventional tumor‐control comparison, further emphasizing the usefulness of mitoSomatic in application. Taken together, our study demonstrates that mitoSomatic is valuable for accurately identifying somatic mtDNA variants in mtDNA NGS data without paired controls, applicable for both tumor and nontumor tissues.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1574-7891Test; https://doaj.org/toc/1878-0261Test

الوصول الحر: https://doaj.org/article/4d36e3c9b71841aeb4d343aaa71d3f52Test

المؤلفون: Min Ji, Liping Su, Li Liu, Mengjie Zhuang, Jinling Xiao, Yaling Guan, Sensen Zhu, Lijuan Ma, Hongwei Pu

المصدر: Scientific Reports, Vol 13, Iss 1, Pp 1-11 (2023)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract Although opioids are necessary for the treatment of acute pain, cancer pain, and palliative care, opioid abuse is a serious threat to society. Heroin (Diacetylmorphine) is the most commonly abused opioid, and it can have a variety of effects on the body's tissues and organs, including the well-known gastrointestinal depression and respiratory depression; however, there is little known about the effects of diacetylmorphine on cardiac damage. Here, we demonstrate that diacetylmorphine induces abnormal electrocardiographic changes in rats and causes damage to cardiomyocytes in vitro by an underlying mechanism of increased autophosphorylation of CaMKII and concomitant regulation of myocardial contractile protein TPM1 and MYOM2 protein expression. The CaMKII inhibitor KN-93 was first tested to rescue the toxic effects of heroin on cardiomyocytes in vitro and the abnormal ECG changes caused by heroin in SD rats, followed by the TMT relative quantitative protein technique to analyze the proteome changes. Diacetylmorphine causes increased phosphorylation at the CaMKII Thr287 site in myocardium, resulting in increased autophosphorylation of CaMKII and subsequent alterations in myocardial contractile proteins, leading to myocardial rhythm abnormalities. These findings provide a theoretical basis for the treatment and prevention of patients with arrhythmias caused by diacetylmorphine inhalation and injection.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/66269f3936e04ac5a0c9a9871ea6a37aTest

المؤلفون: Xin Wang, Jinyong Huang, Liping Su, Qian Ma, Chao Ma, Zengru Xie

المصدر: BMC Infectious Diseases, Vol 23, Iss 1, Pp 1-5 (2023)

مصطلحات موضوعية: Infectious and parasitic diseases, RC109-216

الوصف: Abstract Background Echinococcosis, also known as hydatid disease, is a zoonotic parasitic disease prevalent in pastoral areas, mainly involving the liver and lungs, and less frequently the bones and surrounding soft tissues. Diagnosis and treatment of bone hydatid disease is a challenge, and because of the insidious course of the disease, the lesions are often widely disseminated by the time patients seek medical attention. Case presentation A 29-year-old woman presented with a painless mass that was gradually increasing in size in the cervical thorax. Imaging revealed an enlarged clavicle with multiple bone cortical defects and the existence of cysts in the soft tissues surrounding the clavicle, for which complete excision of the clavicle and the attached cysts was performed. There was no recurrence of the cyst within one year after the operation, and the patient felt well and had normal shoulder joint movement. Conclusions Bone hydatid may appear in bones throughout the body, and cysts that leak from the bone into the surrounding soft tissues may spread at a relatively rapid rate. Prompt surgical removal of the affected bone and surrounding cysts is necessary for treatment.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2334Test

الوصول الحر: https://doaj.org/article/f794c3602023417fbd6739cd4a881126Test

المؤلفون: Ping Li, Yang Liu, Yun Liang, Jian Bo, Sujun Gao, Yongxian Hu, Yu Hu, He Huang, Xiaojun Huang, Hongmei Jing, Xiaoyan Ke, Jianyong Li, Yuhua Li, Qifa Liu, Peihua Lu, Heng Mei, Ting Niu, Yongping Song, Yuqin Song, Liping Su, Sanfang Tu, Jianxiang Wang, Depei Wu, Zhao Wang, Kailin Xu, Zhitao Ying, Qingming Yang, Yajing Zhang, Fengxia Shi, Bin Zhang, Huilai Zhang, Xi Zhang, Mingfeng Zhao, Weili Zhao, Xiangyu Zhao, Liang Huang, Jun Zhu, Wenbin Qian, Weidong Han, Aibin Liang

المصدر: Cancer Biology & Medicine, Vol 20, Iss 2, Pp 129-146 (2023)

مصطلحات موضوعية: car t-cell therapy, b-cell non-hodgkin lymphoma, toxicity, cytokine-release syndrome, clinical management, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Adoptive cellular immunotherapy with chimeric antigen receptor (CAR) T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma (B-NHL). With increasing approval of CAR T-cell products and advances in CAR T cell therapy, CAR T cells are expected to be used in a growing number of cases. However, CAR T-cell-associated toxicities can be severe or even fatal, thus compromising the survival benefit from this therapy. Standardizing and studying the clinical management of these toxicities are imperative. In contrast to other hematological malignancies, such as acute lymphoblastic leukemia and multiple myeloma, anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features, most notably local cytokine-release syndrome (CRS). However, previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL. Consequently, we developed this consensus for the prevention, recognition, and management of these toxicities, on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions. This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management, and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.

وصف الملف: electronic resource

العلاقة: https://www.cancerbiomed.org/content/20/2/129Test; https://doaj.org/toc/2095-3941Test

الوصول الحر: https://doaj.org/article/9444c9c2b3e5428698211ae089d3471aTest