A Single-arm, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetic, Pharmacodynamics and Immunogenicity of PN20 for the Prevention of Chemotherapy-induced Thrombocytopenia in Patients With Lymphoma or Solid Tumor

The main aim of this clinical trial is to assess the safety and tolerability of PN20 in adult patients with chemotherapy-induced thrombocytopenia (CID). The main questions it aims to answer are:
* Is PN20 safe in these patients?
* Could these patients potentially benefit from PN20 prevention? Participants will
* Receive subcutaneous injections of PN20 according to weight on the first day of chemotherapy cycle, within 1 hour before the administration of chemotherapy drugs,
* Visit the clinic on Day 1 (D1), D2, D3, D4, D5, D8, D11, D13, D15 and D21 for assessment.

开始日期2023-12-06

申办/合作机构

重庆派金生物科技有限公司

CTR20233013 / Recruiting临床1期

评价注射用聚乙二醇化促血小板生成肽(PN20) 在化疗所致血小板减少症患者中的单臂、开放标签、单次及多次给药剂量递增研究

主要目的：评价PN20用于成人CIT患者的安全性和耐受性，并通过单、多次给药探索合适的给药剂量及频次，确定Ⅱ期临床试验的推荐剂量和频次。次要目的：①评价PN20在成人CIT患者中单、多次皮下注射给药的药效动力学、药代动力学及免疫原性特征；②评价PN20在成人CIT患者中的初步疗效。

开始日期2023-12-05

申办/合作机构

重庆派金生物科技有限公司

NCT06523088 / Completed临床1期

A Phase 1a Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of PN20 in Healthy Adult Volunteers

The main aim of this clinical trial is to assess the safety of PN20 in healthy volunteers aged 18 to 50 years. The main questions it aims to answer are:
* Is PN20 safe in adult? Researchers will compare PN20 to a placebo (a look-alike substance that contains no drug) to see if PN20 is safe.
Participants will
* Receive a single dose injection of PN20 or placebo according to weight,
* Stay in hospital for assessment.

开始日期2022-06-16

申办/合作机构

重庆派金生物科技有限公司

100 项与 TPO receptor x EPO receptor 相关的临床结果

登录后查看更多信息

100 项与 TPO receptor x EPO receptor 相关的转化医学

登录后查看更多信息

0 项与 TPO receptor x EPO receptor 相关的专利（医药）

登录后查看更多信息

项与 TPO receptor x EPO receptor 相关的文献（医药）

2024-04-01·Annals of Anatomy - Anatomischer Anzeiger

Spatiotemporal expression profiles of c-Mpl mRNA in the tooth germ: Comparative expression dynamics of vascularization-related genes

Article

作者: Shimada, Kazuto ; Suzuki, Kingo ; Sunohara, Masataka ; Morikawa, Shigeru

BACKGROUNDVascularization is an essential event for both embryonic organ development and tissue repair in adults. During mouse tooth development, endothelial cells migrate into dental papilla during the cap stage, and form blood vessels through angiogenesis. Megakaryocytes and/or platelets, as other hematopoietic cells, express angiogenic molecules and can promote angiogenesis in adult tissues. However, it remains unknown which cells are responsible for attracting and leading blood vessels through the dental papilla during tooth development.METHODSHere we analyzed the spatiotemporal expression of c-Mpl mRNA in developing molar teeth of fetal mice. Expression patterns were then compared with those of several markers of hematopoietic cells as well as of angiogenic elements including CD41, erythropoietin receptor, CD34, angiopoietin-1 (Ang-1), Tie-2, and vascular endothelial growth factor receptor2 (VEGFR2) through in situ hybridization or immunohistochemistry.RESULTSCells expressing c-Mpl mRNA was found in several parts of the developing tooth germ, including the peridental mesenchyme, dental papilla, enamel organ, and dental lamina. This expression occurred in a spatiotemporally controlled fashion. CD41-expressing cells were not detected during tooth development. The spatiotemporal expression pattern of c-Mpl mRNA in the dental papilla was similar to that of Ang-1, which preceded invasion of endothelial cells. Eventually, at the early bell stage, the c-Mpl mRNA signal was detected in morphologically differentiating odontoblasts that accumulated in the periphery of the dental papilla along the inner enamel epithelium layer of the future cusp region.CONCLUSIONDuring tooth development, several kinds of cells express c-Mpl mRNA in a spatiotemporally controlled fashion, including differentiating odontoblasts. We hypothesize that c-Mpl-expressing cells appearing in the forming dental papilla at the cap stage are odontoblast progenitor cells that migrate to the site of odontoblast differentiation. There they attract vascular endothelial cells into the forming dental papilla and lead cells toward the inner enamel epithelium layer through production of angiogenic molecules (e.g., Ang-1) during migration to the site of differentiation. C-Mpl may regulate apoptosis and/or proliferation of expressing cells in order to execute normal development of the tooth.

2023-07-01·Omics : a journal of integrative biology

Whole Exome Sequencing Reveals Novel Variants in Unexplained Erythrocytosis.

Article

作者: Premdeep, Harikrishnan ; Subramanian, Shankar ; Garapati, Kishore ; Pandey, Akhilesh ; Muthusamy, Babylakshmi ; Khurana, Harshit ; Yanamandra, Uday

Erythrocytosis is characterized by an increase in red cells in peripheral blood. Polycythemia vera, the commonest primary erythrocytosis, results from pathogenic variants in JAK2 in ∼98% of cases. Although some variants have been reported in JAK2-negative polycythemia, the causal genetic variants remain unidentified in ∼80% of cases. To discover genetic variants in unexplained erythrocytosis, we performed whole exome sequencing in 27 patients with JAK2-negative polycythemia after excluding the presence of any mutations in genes previously associated with erythrocytosis (EPOR, VHL, PHD2, EPAS1, HBA, and HBB). We found that the majority of patients (25/27) had variants in genes involved in epigenetic processes, including TET2 and ASXL1 or in genes related to hematopoietic signaling such as MPL and GFIB. Based on computational analysis, we believe that variants identified in 11 patients in this study could be pathogenic although functional studies will be required for confirmation. To our knowledge, this is the largest study reporting novel variants in individuals with unexplained erythrocytosis. Our results suggest that genes involved in epigenetic processes and hematopoietic signaling pathways are likely associated with unexplained erythrocytosis in individuals lacking JAK2 mutations. With very few previous studies targeting JAK2-negative polycythemia patients to identify underlying variants, this study opens a new avenue in evaluating and managing JAK2-negative polycythemia.

2022-04-01·Leukemia1区 · 医学

Erythropoietin receptor contributes to thrombopoietin receptor (Mpl)-independent thrombocytopoiesis in zebrafish

1区 · 医学

Letter

作者: Sun, Ying ; Lin, Qing ; Lian, Junwei ; Wu, Jiaye ; Meng, Panpan ; Wu, Liangliang ; Zhang, Yiyue

These results provide in vivo genetic evidence for the role of epor in mpl-independent thrombocytopoiesis in zebrafish.This evidence for epor-mediated thrombocytopoiesis, which might be conserved in vertebrates, may further our understanding of thrombocyte biol. as well as highlight potential therapeutic applications for the treatment of platelet related disorders.We further explored the role of epor in thrombocytopoiesis using epor-knockout zebrafish (epor^szy3) generated by CRISPR/Cas9.