Pilot Study of the Antibody-drug Conjugate Glembatumumab Vedotin (CDX-011) Following Doxorubicin (Adriamycin) and Cytoxan as Neo-adjuvant Therapy in Glycoprotein NMB-expressing High Risk Triple Negative Breast Cancer

This is a single arm, pilot study assessing safety/feasibility and efficacy of neo-adjuvant glembatumumab vedotin (GV) in patients with high risk triple negative breast cancer (TNBC) with glycoprotein-NMB (gpNMB) expression ≥ 25%. Primary endpoints will be safety/feasibility, and secondary endpoints will be rates of pathologic complete response (pCR), and measurements of growth differentiation factor-11 (GDF11) and glycoprotein NMB (gpNMB) expression.

Start Date01 May 2018

Sponsor / Collaborator

University of Virginia

[+1]

NCT03326258 / WithdrawnPhase 1/2IIT

Phase Ib/II Clinical Trial of Glembatumumab Vedotin and Nivolumab in Advanced Solid Tumors

This phase Ib/II trial studies the best dose of glembatumumab vedotin when giving together with nivolumab and ipilimumab in treating patients with solid tumor that has spread to other places in the body and cannot be removed by surgery. Monoclonal antibodies, such as glembatumumab vedotin, nivolumab, and ipilimumab, may interfere with the ability of tumor cells to grow and spread.

Start Date20 Apr 2018

Sponsor / Collaborator

National Cancer Institute

ACTRN12617001621303 / WithdrawnPhase 1

FLIGHT Protocol: An Open Label Phase 1 Study Investigating the Effects of CDX-301 on the Safety, Clinical Activity, and Immune Priming of Glembatumumab Vedotin Combined with Pembrolizumab or Nivolumab in Unresectable or Metastatic Melanoma Patients Not Responding to the Anti-PD1 Therapy

Start Date04 Feb 2018

Sponsor / Collaborator

Central Adelaide Local Health Network, Inc.

100 Clinical Results associated with GPNMB

100 Translational Medicine associated with GPNMB

0 Patents (Medical) associated with GPNMB

996

Literatures (Medical) associated with GPNMB

01 Dec 2024·Annals of Diagnostic Pathology

Implication of KMT2C and TSC2 variants in the tumorigenesis of acquired cystic disease-associated renal cell carcinomas

Article

Author: Kojima, Fumiyoshi ; Iwamoto, Ryuta ; Kohjimoto, Yasuo ; Sagan, Kanako ; Musangile, Fidele Yambayamba ; Matsuzaki, Ibu ; Murata, Shin-Ichi ; Mikasa, Yurina ; Hara, Isao

In 2020, acquired cystic disease-associated renal cell carcinomas (ACD-RCCs) were reported to harbor KMT2C and TSC2 variants: however, their carcinogenic implication has not yet been reported. This study aimed to explore the variant features of KMT2C and TSC2 in ACD-RCC and their implication in ACD-RCC tumorigenesis. Eleven ACD-RCCs, 10 ACD-RCC-like cysts, and 18 background kidneys were retrieved. The background kidneys consisted of atrophic thyroid follicle-like tubules. They included four with clustered cysts, two with eosinophilic changes, and one each with clear cell changes and sieve-like changes in the renal tubules. First, DNA-targeted sequencing of KMT2C and TSC2 whole exons was performed on eight ACD-RCC samples. Subsequently, a custom DNA panel was designed to include the recurrent KMT2C and TSC2 variants based on the sequencing results. Second, DNA-targeted sequencing was performed on the remaining samples using a custom panel targeting the recurrent variants. Additionally, immunohistochemistry was performed for KMTC, H3K4me1, H3K4me3, TSC2, and GPNMB on the ACD-RCCs. Six of the 11 ACD-RCC cases harbored KMT2C and TSC2 variants, including nine likely pathogenic variants. In contrast to ACD-RCC, 1 of the 9 ACD-RCC-like cysts harbored both variants. Immunohistochemical analysis did not support the loss of function in ACD-RCCs harboring KMT2C and TSC2 variants. KMT2C and TSC2 variant frequencies were higher in ACD-RCC than in other renal cell carcinomas. However, KMT2C and TSC2 are unlikely to be the primary drivers of ACD-RCC development.

01 Nov 2024·International Journal of Biological Macromolecules

Single-cell RNA sequencing revealed the roles of macromolecule epidermal growth factor receptor (EGFR) in the hybrid sterility of hermaphroditic Argopecten scallops

Article

Author: Yu, Tieying ; Fan, Jiawei ; Lu, Xia ; Ning, Junhao ; Xu, Xin ; Wang, Chunde ; Liu, Guilong ; Chen, Rongjie

The macromolecule epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that belongs to the protein kinase superfamily, which plays versatile functions in cell proliferation, development and fertility regulation. Almost all F₁ hybrids obtained from the hermaphroditic bay scallops and Peruvian scallops exhibit infertility, and the genetic mechanism remains unclear. In this study, the comprehensive scRNA-seq was first conducted in the gonads of hybrid scallops, deducing the developmental sequence of germ cells and identifying the critical regulators in hybrid sterility: epidermal growth factor receptor. During the development from oogenesis phase germ cells to oocytes, the expression of the EGFR gene gradually decreased in sterile hybrids but increased in fertile hybrids. The significantly lower EGFR expression and ATP content, but higher ROS production rate was detected in the gonad of sterile hybrids than that in fertile hybrids, which might cause slow development of oocytes, stagnation of cell cycle, insufficient energy supply, high level of apoptosis and final sterility. Specific knock-down of EGFR gene led to decreased ATP content, increased ROS production rate, and inhibited oocyte maturation and gonadal development. These findings provide new insights into the roles of EGFR in hybrid infertility of bivalves and the healthy development of scallop breeding.

15 Oct 2024·Journal of Clinical Investigation

Spatiotemporal transcriptomic mapping of regenerative inflammation in skeletal muscle reveals a dynamic multilayered tissue architecture

Article

Author: Oleksak, Darby ; Wei, Xiaoyan ; Patsalos, Andreas ; Nagy, Gergely ; Halasz, Laszlo ; Nagy, Laszlo ; Tzerpos, Petros ; Sweeney, H Lee ; Conrad, Thomas ; Hammers, David W

Tissue regeneration is orchestrated by macrophages that clear damaged cells and promote regenerative inflammation. How macrophages spatially adapt and diversify their functions to support the architectural requirements of actively regenerating tissue remains unknown. In this study, we reconstructed the dynamic trajectories of myeloid cells isolated from acutely injured and early stage dystrophic muscles. We identified divergent subsets of monocytes/macrophages and DCs and validated markers (e.g., glycoprotein NMB [GPNMB]) and transcriptional regulators associated with defined functional states. In dystrophic muscle, specialized repair-associated subsets exhibited distinct macrophage diversity and reduced DC heterogeneity. Integrating spatial transcriptomics analyses with immunofluorescence uncovered the ordered distribution of subpopulations and multilayered regenerative inflammation zones (RIZs) where distinct macrophage subsets are organized in functional zones around damaged myofibers supporting all phases of regeneration. Importantly, intermittent glucocorticoid treatment disrupted the RIZs. Our findings suggest that macrophage subtypes mediated the development of the highly ordered architecture of regenerative tissues, unveiling the principles of the structured yet dynamic nature of regenerative inflammation supporting effective tissue repair.

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