A Single-Center, Exploratory Study of BTLA Inhibitor (JS004) Combined with Toripalimab and Chemotherapy in the Perioperative Treatment of Resectable Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma

This is a single-center, single-arm, phase II study, aiming to preliminarily explore the efficacy and safety of JS004 combined with toripalimab and chemotherapy for perioperative treatment of locally advanced thoracic esophageal squamous cell carcinoma that is resectable. The plan is to enroll 20 patients with locally advanced resectable thoracic esophageal cancer. In the neoadjuvant treatment phase, patients will receive JS004 + toripalimab + chemotherapy (paclitaxel + cisplatin) for 2 cycles. This will be followed by the surgical phase: surgery will be performed 3-8 weeks after the last dose of neoadjuvant treatment. In the postoperative maintenance treatment phase, maintenance treatment will start 4 weeks ± 7 days after surgery, but no later than 10 weeks after surgery. For patients with R0 resection confirmed by postoperative pathology, they will receive maintenance treatment with JS004 + toripalimab for up to 15 cycles. For patients with non-R0 resection, they will receive maintenance treatment with JS004 + toripalimab combined with standard radiation or chemotherapy (selected by the investigator based on esophageal cancer guidelines). During the study, the maximum number of cycles of JS004 combined with toripalimab is 17 cycles (approximately 1 year).

开始日期2024-09-30

申办/合作机构

河南省人民医院

NCT06444009 / Recruiting临床2期IIT

Neoadjuvant Immunotherapy in Combination With Chemotherapy in Resectable Head and Neck Cancer：A Randomized, Phase II Study

A Randomized, Phase II Study of ivonescimab or cadonilimab or penpulimab in Combination With Cisplatin and Nab-paclitaxel in Patients With locally advanced head and neck squamous cell carcinoma (HNSCC) eligible for resection.
This proposed study will evaluate the efficacy and safety of preoperative administration of ivonescimab or cadonilimab or penpulimab combined with chemotherapy in HNSCC who are eligible for resection.

开始日期2024-07-01

申办/合作机构

四川大学华西医院（四川省国际医院）

NCT05520619 / Active, not recruiting临床2期IIT

Tislelizumab Plus Induction Chemotherapy Followed by Concurrent Chemoradiotherapy for Patients with Locally Advanced Esophageal Squamous Cell Carcinoma: a Phase II, Randomized Trial (EC-CRT-002)

Definitive chemoradiotherapy (CRT) is the standard treatment option for unresectable locally advanced esophageal cancer (EC). However, as high as more than 40% of EC patients experienced locoregional recurrence after concurrent CRT. Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced EC. Recently, the combination of immunotherapy with CRT has emerged as a promising strategy to improve clinical outcomes in EC. The aim of this study was to evaluate whether the efficacy of tislelizumab (an anti-PD-1 antibody) plus induction chemotherapy followed by concurrent chemoradiotherapy would achieve a ≥71% 1-year progression-free survival rate, surpassing the historical 56% rate (NCT02403531) in patients with locally advanced esophageal squamous cell carcinoma (ESCC).

开始日期2022-09-15

申办/合作机构

中山大学

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100 项与紫杉醇/顺铂相关的临床结果

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100 项与紫杉醇/顺铂相关的转化医学

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100 项与紫杉醇/顺铂相关的专利（医药）

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3,204

项与紫杉醇/顺铂相关的文献（医药）

2024-12-31·Scandinavian cardiovascular journal : SCJ

Molecular mechanism of triptolide in myocardial fibrosis through the Wnt/β-catenin signaling pathway

Article

作者: Zhang, Yiwen ; Lu, Feng

Objective. Myocardial fibrosis (MF) is a common manifestation of end-stage cardiovascular diseases. Triptolide (TP) provides protection against cardiovascular diseases. This study was to explore the functional mechanism of TP in MF rats via the Wnt/β-catenin pathway. Methods. The MF rat model was established via subcutaneous injection of isoproterenol (ISO) and treated with low/medium/high doses of TP (L-TP/M-TP/H-TP) or Wnt agonist BML-284. Cardiac function was examined by echocardiography. Pathological changes of myocardial tissues were observed by HE and Masson staining. Col-I/Col-III/Vimentin/α-SMA levels were detected by immunohistochemistry, RT-qPCR, and Western blot. Collagen volume fraction content was measured. Expression levels of the Wnt/β-catenin pathway-related proteins (β-catenin/c-myc/Cyclin D1) were detected by Western blot. Rat cardiac fibroblasts were utilized for in vitro validation experiments. Results. MF rats had enlarged left ventricle, decreased systolic and diastolic function and cardiac dysfunction, elevated collagen fiber distribution, collagen volume fraction and hydroxyproline content. Levels of Col-I/Col-III/Vimentin/α-SMA, and protein levels of β-catenin/c-myc/Cyclin D1 were increased in MF rats. The Wnt/β-catenin pathway was activated in the myocardial tissues of MF rats. TP treatment alleviated impairments of cardiac function and myocardial tissuepathological injury, decreased collagen fibers, collagen volume fraction, Col-I, Col-III, α-SMA and Vimentin levels, HYP content, inhibited Wnt/β-catenin pathway, with H-TP showing the most significant effects. Wnt agonist BML-284 antagonized the inhibitive effect of TP on MF. TP inhibited the Wnt/β-catenin pathway to repress the proliferation and differentiation of mouse cardiac fibroblasts in vitro. Conclusions. TP was found to ameliorate ISO-induced MF in rats by inhibiting the Wnt/β-catenin pathway.

2024-12-31·Pharmaceutical biology

Comparative efficacy and safety of Chinese medicine injections as an adjunctive therapy for cervical cancer in Chinese patients: a network meta-analysis

Review

作者: Xie, Hui ; Wang, Zihong ; Zhang, Di ; Liu, Xianghong ; Sun, Shiguang ; Wang, Qun ; Song, Haiyan ; Zhang, Hongxing ; Ma, Fei

CONTEXT:

Chinese medicine injections (CMIs) are widely used as adjuvant therapy for cervical cancer in China. However, the effectiveness of different types of CMIs remains uncertain.

OBJECTIVE:

To assess the effectiveness and safety of CMIs when used in conjunction with radiotherapy (RT) or concurrent chemoradiotherapy (CCRT), particularly in combination with cisplatin (DDP), docetaxel plus cisplatin (DP), and paclitaxel plus cisplatin (TP).

MATERIALS AND METHODS:

Randomized controlled trials (RCTs) were searched in databases including CNKI, WanFang, VIP, SinoMed, PubMed, Cochrane Library, Embase, and Web of Science from inception to September 2023. We calculated the risk ratio with a 95% confidence interval and the surface under the cumulative ranking area curve (SUCRA) for the clinical efficacy rate (CER), the efficacy rate by Karnofsky Performance Status (KPS), and the rates of leukopenia reduction (LRR) and gastrointestinal reactions (GRR).

RESULTS:

Forty-seven RCTs were included, including nine CMI types: Aidi, Fufangkushen, Huangqi, Kangai (KA), Kanglaite (KLT), Renshenduotang, Shenqifuzheng (SQFZ), Shenmai (SM), and Yadanzi. KLT and KA were likely optimal choices with radiotherapy for CER and KPS, respectively. KA and KLT were optimal choices with RT + DDP for CER and GRR, respectively. KLT was the likely optimal choice with RT + DP for CER and KA for both KPS and GRR. SM and SQFZ were the likely optimal choices with RT + TP for CER and LRR, respectively.

CONCLUSIONS:

The optimal recommendation depends on whether CMIs are used with radiotherapy or concurrent chemoradiotherapy. More high-quality RCTs are needed to confirm further and update the existing evidence.

2024-10-01·European urology oncology

Transperineal Versus Transrectal Magnetic Resonance Imaging–targeted Biopsies for Prostate Cancer Diagnosis: Final Results of the Randomized PERFECT trial (CCAFU-PR1)

Article

作者: Almeras, Christophe ; Aziza, Richard ; Rozet, François ; Giannarini, Gianluca ; Ploussard, Guillaume ; Renard-Penna, Raphaële ; Lenfant, Louis ; Rouprêt, Morgan ; Descotes, Jean-Luc ; Barret, Eric ; Beauval, Jean-Baptiste ; Salin, Ambroise ; Malavaud, Bernard ; Fiard, Gaëlle

BACKGROUND:

Recent guidelines favor transperineal (TP) prostate biopsies over the transrectal (TR) approach due to a reduced sepsis risk. Yet, evidence from controlled trial comparing both approaches within the MRI-targeted pathway for significant prostate cancer (PCa) detection is lacking.

OBJECTIVE:

To compare the significant PCa detection rate between magnetic resonance imaging (MRI)-targeted TR and TP approaches in biopsy-naïve patients.

DESIGN, SETTING, AND PARTICIPANTS:

In this noninferiority controlled trial, we randomized (ratio 1:1) 270 MRI-positive biopsy-naïve patients.

INTERVENTION:

MRI-targeted TP versus TR biopsy.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES:

The primary outcome was the detection rate of significant PCa (International Society of Urological Pathology [ISUP] ≥2) in MRI-targeted biopsies. Secondary outcomes were any-grade PCa detection, detection on concomitant systematic biopsy, complications, and functional outcomes.

RESULTS AND LIMITATIONS:

Targeted biopsies identified significant PCa in 47.2% of TP and 54.2% of TR participants (-7%, p = 0.6235). On a per-lesion analysis, posterior lesions yielded higher detection rates via TR (59.0% vs 44.3%, p = 0.0443), while anterior lesions were more frequently detected via TP (40.6% vs 26.5%, p = 0.2228). The overall (any grade) cancer detection rate in targeted biopsies was comparable between groups: 71.3% (TP) versus 64.1% (TR; p = 0.2209) with significantly more ISUP 1 cases detected in the TP arm. Adverse events of grade ≥2 were not different between TP (35.7%) and TR (40.5%, p = 0.4256). One TR patient (0.8%) experienced grade 3 sepsis. Quality of life, and urinary and sexual function, as well as pain scores, were comparable between groups.

CONCLUSIONS:

Despite a comparable overall detection rate for any-grade PCa, noninferiority of TP over TR for MRI-targeted biopsies for significant PCa detection was not demonstrated. However, MRI lesion location influenced biopsy route performance, suggesting that a pragmatic approach based on lesion location might enhance significant PCa assessment.

PATIENT SUMMARY:

This trial compared the efficacy and safety of two biopsy approaches for prostate cancer diagnosis. Both approaches seem complementary according to the lesion location.

项与紫杉醇/顺铂相关的新闻（医药）

2024-07-25

·今日头条

【Nature子刊】新突破！中山医院舒先红团队：可吸入心脏靶向纳米颗粒，治疗慢性心力衰竭！

本文为转化医学网原创，转载请注明出处作者：Tracy 【导读】心力衰竭在世界范围内，导致相当大的发病率和死亡率。临床上用于治疗心力衰竭的药物，仍然受到心脏递送效率低和脱靶消耗的严重限制。受吸入药物高心脏递送效率的启发，团队提出了一种可吸入心脏靶向肽（CTP）修饰的磷酸钙（CaP）纳米颗粒，用于递送PDE10A的选择性抑制剂TP-10。 2024年7月18日，复旦大学附属中山医院舒先红团队在期刊《Nature Communications》上发表了题为“Inhalable cardiac targeting peptide modified nanomedicine prevents pressure overload heart failure in male mice”的研究论文。本研究强调，使用经过CTP修饰并通过心肺循环给药的工程化TP-10@CaP-CTP纳米颗粒，可能是长期管理慢性心力衰竭的一种有前途的方法。 https://www-nature-com.libproxy1.nus.edu.sg/articles/s41467-024-50312-1 研究背景 01 心力衰竭是人类发病和死亡的主要原因，影响着全球2,600多万人。随着世界人口老龄化，全球心力衰竭负担不可避免地增加，预计未来将大幅增加。近年来，在对心力衰竭分子生物学和靶点的探索方面，取得了显著进展。然而，许多患者仍然预后不良，生活质量低下。因此，当务之急是探索预防心力衰竭的替代给药策略。口服途径是日常心力衰竭治疗中，使用最广泛的给药途径，因为它是非侵入性的，可促进患者对长期用药的依从性。然而，一些物理屏障（例如，肠上皮、肠粘液、肠道微生物和毛细血管屏障）限制了药物在肠膜上的有效运输。此外，胃肠道中的化学物质（包括胃液、蛋白酶、消化液或胆盐）和肝脏中的代谢反应，可能会阻止治疗药物外渗靶组织。这些缺点使得口服给药，对于心力衰竭的长期治疗不可靠。其他侵入性给药策略，如静脉内（I.V.）注射、手术方法或基于导管的方法，在一定程度上，提高了药物输送到心脏的效率，但可能导致患者的依从性差，并且通常伴随着不可避免的心肌损伤并发症。本研究制备了一种负载TP-10的CTP修饰的可生物降解CaP纳米颗粒（简称TP-10@CaP-CTP），并通过吸入输送到心肌，用于慢性心力衰竭的长期治疗。TP-10是PDE10A的选择性抑制剂，已被证明参与心力衰竭的病理过程。在慢性心力衰竭小鼠模型中使用TP-10，可以减弱心肌细胞（CM）肥大，抑制心肌成纤维细胞（CF）的活化、增殖和迁移，以及细胞外基质（ECM）合成，从而逆转已建立的心脏重塑，并改善心脏功能。与其他PDE抑制剂相比，TP-10通过调节细胞内cAMP和cGMP水平，影响CMs和CFs。此外，PED10A在II期临床试验中，被证明是一个安全的治疗靶点。这些双重治疗效果和安全特性，使TP-10成为一种有前途的小分子，可以预防心力衰竭的发病机制。研究进展 02 吸入TP-10@CaP-CTP在压力超负荷诱导的心力衰竭小鼠模型中的疗效小鼠吸入不同处理剂（PBS、CaP-CTP、TP-10、TP-10@CaP和TP-10@CaP-CTP）后，确定通过吸入处理TP-10@CaP-CTP，可显著提高心力衰竭模型小鼠的长期生存率。此外，治疗6周后，PBS和CaP-CTP治疗组的心脏，以及心脏重量/体重比，明显更大，比假手术组做得更好。与TP-10和TP-10@CaP治疗相比，TP-10@CaP-CTP吸入治疗，显著改善了CM肥大，并表现出更好的治疗效果。吸入TP-10@CaP-CTP的小鼠的血浆ANP水平（心力衰竭的生物标志物），也显著降低。吸入TP-10@CaP-CTP的小鼠心肌中，标记物表达显著下调。静脉注射TP-10@CaP-CTP后，对比TAC对心力衰竭的影响，不如吸入TP-10@CaP-CTP后明显。这些数据表明， TP-10@CaP-CTP吸入治疗在相对较低的剂量下，有效减弱了慢性心力衰竭的病理过程。吸入TP-10@CaP-CTP在压力过载诱导的心力衰竭小鼠模型中的疗效。吸入TP-10@CaP-CTP对心脏功能的影响超声心动图显示，TP-10@CaP-CTP治疗可显著改善心脏收缩功能参数的时间依赖性恶化，包括射血分数（EF%）和分数缩短（FS%）。在接受TP-10@CaP-CTP的小鼠中，左心室收缩末期直径（LVESD）和左心室舒张末期直径（LVEDD）明显改善。此外，吸入TP-10@CaP-CTP也显著改善了心脏舒张功能参数E/A比值。与超声心动图结果一致，TP-10@CaP-CTP处理的小鼠的AMCMs，表现出明显的收缩功能改善。研究结果表明，TP-10@CaP-CTP吸入治疗，可有效改善TAC诱导的心力衰竭小鼠的心脏收缩和舒张功能。 TP-10@CaP-CTP吸入治疗，具有显著的心脏保护作用。吸入TP-10@CaP-CTP纳米颗粒的生物安全性评价与对照组相比，TP-10@CaP-CTP吸入治疗组，未观察到明显的炎症浸润或纤维化。表示肺水肿程度的吸入治疗组肺W/D比值，在不同时间点，没有显著增加。ELISAs结果显示，吸入治疗组与对照组的IL-1β、IL-6和TNF-α水平，无明显差异。此外，团队在治疗6周后，收获了肺组织。这些数据表明，低剂量的长期吸入治疗（小鼠为2.5mg / kg / 2天）或高剂量的短期至中期吸入治疗（小鼠为7.5mg / kg / 2天），可能不会导致肺损伤。吸入治疗组血清IL-1β、IL-6、TNF-α水平，无明显升高。H&E染色显示，吸入治疗组主要器官（肺、肝、肾、脾、脑），无明显组织病理学改变。此外，血浆C3、C3b或C3c水平，没有显著增加。这些结果表明， TP-10@CaP-CTP纳米颗粒，具有良好的生物相容性和安全性。吸入TP-10@CaP-CTP对心脏功能的影响。研究结论 03 本研究的主要目的是提出一种心脏靶向肽（CTP）工程策略，以促进纳米药物在衰竭心肌中的积累。体外和体内研究表明，在压力过载心力衰竭小鼠模型中，CTP显著促进了CaP纳米颗粒对衰竭心肌的靶向，并且这种靶向仅在心脏处于病理状态时发生。研究数据表明，CMs和CFs在病理刺激下都是靶向的。有趣的是，肺上皮细胞和成纤维细胞并不是这种CTP修饰的纳米药物的靶向。团队推测，在病理条件下， CTP的靶向能力可能是由CMs和CFs中的特定蛋白质或受体组合介导的。尽管这项研究取得了令人鼓舞的结果，但目前制定的策略的治疗效果，与临床实践相比，并未显示出实质性的进步。因此，未来的研究，应侧重于基于吸入的方法的系统优化，包括通过有针对性的设计，来优化涉及雾化效率、药物负荷和在心脏中积累的各种参数。此外，一些病理性肺部疾病（如慢性阻塞性肺病），可能会阻碍药物通过心肺循环吸收。总之，团队提出了一种可吸入的心脏靶向纳米颗粒TP-10@CaP-CTP，用于慢性心力衰竭的长期治疗。通过吸入和CTP修饰给药的高递送效率，允许靶向病理性心肌并改善纳米药物的局部积累，从而获得更好的治疗效果，并避免不良肺部反应。输送到衰竭的心肌后，CaP壳分解，释放TP-10，可有效减弱心脏重塑，改善心脏功能。此外，吸入TP-10@CaP-CTP在压力超载诱导的小鼠模型中，显示出更好的治疗效果。本研究验证了CTP治疗压力超负荷心力衰竭的可行性，证实了可吸入CaP纳米颗粒长期治疗的生物安全性。尽管这项概念验证工作仍处于早期阶段，但团队设想这种基于心肺循环递送的策略，对慢性心力衰竭的长期管理具有很大的前景。参考资料： 1.Heidenreich, P. A. et al. AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 145, e876–e894 (2022). 2.Bloom, M. W. et al. Heart failure with reduced ejection fraction. Nat. Rev. Dis. Prim. 3, 17058 (2017). 【关于投稿】转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 北京｜09月20日-21日 ▶ 第五届单细胞技术应用研讨会暨空间组学前沿研讨会欢迎您的参与！点击对应文字查看详情

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