This study will test the safety of a drug called SGN-ALPV in participants with solid tumors. It will also study the side effects of this drug. A side effect is anything a drug does to your body besides treating your disease.
Participants will have solid tumor cancer that has spread through the body (metastatic) or cannot be removed with surgery (unresectable).
This study will have three parts. Parts A and B of the study will find out how much SGN-ALPV should be given to participants. Part C will use the dose and schedule found in Parts A and B to find out how safe SGN-ALPV is and if it works to treat solid tumor cancers.

Start Date21 Apr 2022

Sponsor / Collaborator

Seagen Inc.

NCT04627740 / RecruitingPhase 1/2IIT

A Single-Arm, Single-Center, Open-Label Pilot Study of Anti-ALPP CART-cells in Patient With Alkaline Phosphatase, Placental (ALPP)-Positive Advanced Solid Tumor

The goal of this clinical trial is to evaluate the safety and efficacy of anti-ALPP chimeric antigen receptor (CAR)-modified T (CAR-T) cells in treating patients with ALPP-positive Advanced Solid Tumors.

Start Date01 Dec 2020

Sponsor / Collaborator

Xinqiao Hospital

[+1]

NCT06556108 / RecruitingPhase 1/2IIT

A Single-Arm, Single-Center, Open-Label Pilot Study of Anti-ALPP CAR-T Cells for Alkaline Phosphatase, Placental (ALPP)-Positive Advanced Solid Tumors

Alkaline phosphatase (ALP) is a membrane-bound glycoprotein that catalyzes the hydrolysis of phosphates at alkaline pH values. As one of the earliest discovered oncofetal antigens, ALP has emerged as a significant biomarker for various malignant tumors, such as ovarian cancer, breast cancer, trophoblastic tumors, germ cell tumors, endometrial cancer, testicular tumors, cervical intraepithelial neoplasia, and gastrointestinal tumors.

Start Date01 Jan 2018

Sponsor / Collaborator

Xinqiao Hospital

100 Clinical Results associated with ALPP

100 Translational Medicine associated with ALPP

0 Patents (Medical) associated with ALPP

323

Literatures (Medical) associated with ALPP

01 Sep 2024·Heliyon

Functional characterization of the SDR42E1 reveals its role in vitamin D biosynthesis

Article

Author: Ericsson, Johan ; Hendi, Nagham Nafiz ; Nemer, Georges ; Bengoechea-Alonso, Maria Teresa

Vitamin D deficiency poses a widespread health challenge, shaped by environmental and genetic determinants. A recent discovery identified a genetic regulator, rs11542462, in the SDR42E1 gene, though its biological implications remain largely unexplored. Our bioinformatic assessments revealed pronounced SDR42E1 expression in skin keratinocytes and the analogous HaCaT human keratinocyte cell lines, prompting us to select the latter as an experimental model. Employing CRISPR/Cas9 gene-editing technology and multi-omics approach, we discovered that depleting SDR42E1 showed a 1.6-fold disruption in steroid biosynthesis pathway (P-value = 0.03), considerably affecting crucial vitamin D biosynthesis regulators. Notably, SERPINB2 (P-value = 2.17 × 10^-103), EBP (P-value = 2.46 × 10^-13), and DHCR7 (P-value = 8.03 × 10^-09) elevated by ∼2-3 fold, while ALPP (P-value <2.2 × 10^-308), SLC7A5 (P-value = 1.96 × 10^-215), and CYP26A1 (P-value = 1.06 × 10^-08) downregulated by ∼1.5-3 fold. These alterations resulted in accumulation of 7-dehydrocholesterol precursor and reduction of vitamin D₃ production, as evidenced by the drug enrichment (P-value = 4.39 × 10^-06) and total vitamin D quantification (R² = 0.935, P-value = 0.0016) analyses. Our investigation unveils SDR42E1's significance in vitamin D homeostasis, emphasizing the potential of precision medicine in addressing vitamin D deficiency through understanding its genetic basis.

01 Jul 2024·Alzheimer's & Dementia

The presenilin 1 mutation P436S causes familial Alzheimer's disease with elevated Aβ43 and atypical clinical manifestations

Article

Author: Arber, Charles ; Fox, Nick C. ; O'Connor, Antoinette ; Gabriele, Rebecca ; Wray, Selina ; Ryan, Natalie S. ; Buhidma, Yazead ; Tomczuk, Filip ; Lashley, Tammaryn ; Farrell, Clíona ; Rice, Helen ; Belder, Christopher R. S.

AbstractINTRODUCTIONFamilial Alzheimer's disease (fAD) is heterogeneous in terms of age at onset and clinical presentation. A greater understanding of the pathogenicity of fAD variants and how these contribute to heterogeneity will enhance our understanding of the mechanisms of AD more widely.METHODSTo determine the pathogenicity of the unclassified PSEN1 P436S mutation, we studied an expanded kindred of eight affected individuals, with magnetic resonance imaging (MRI) (two individuals), patient‐derived induced pluripotent stem cell (iPSC) models (two donors), and post‐mortem histology (one donor).RESULTSAn autosomal dominant pattern of inheritance of fAD was seen, with an average age at symptom onset of 46 years and atypical features. iPSC models and post‐mortem tissue supported high production of amyloid beta 43 (Aβ43). PSEN1 peptide maturation was unimpaired.DISCUSSIONWe confirm that the P436S mutation in PSEN1 causes atypical fAD. The location of the mutation in the critical PSEN1 proline‐alanine‐leucine‐proline (PALP) motif may explain the early age at onset despite appropriate protein maturation.Highlights

PSEN1 P436S mutations cause familial Alzheimer's disease.

This mutation is associated with atypical clinical presentation.

Induced pluripotent stem cells (iPSCs) and post‐mortem studies support increased amyloid beta (Aβ43) production.

Early age at onset highlights the importance of the PALP motif in PSEN1 function.

01 Feb 2024·International Journal of Biological Macromolecules

Plantago asiatica L. polysaccharides: Physiochemical properties, structural characteristics, biological activity and application prospects: A review

Review

Author: Wang, Xiaotong ; Xie, Li ; Gao, Song ; Huan, Changchao ; Zhang, Ruizhen ; Wang, Xiaobing ; Wang, Xingyu ; Yao, Jingting

Plantago asiatica L. (PAL), a traditional herb, has been used in East Asia for thousands of years. In recent years, polysaccharides extracted from PAL have garnered increased attention due to their outstanding pharmacological and biological properties. Previous research has established that PAL-derived polysaccharides exhibit antioxidant, anti-inflammatory, antidiabetic, antitumor, antimicrobial, immune-regulatory, intestinal health-promoting, antiviral, and other effects. Nevertheless, a comprehensive summary of the research related to Plantago asiatica L. polysaccharides (PALP) has not been reported to date. In this paper, we review the methods for isolation and purification, physiochemical properties, structural features, and biological activities of PALP. To provide a foundation for research and application in the fields of medicine and food, this review also outlines the future development prospects of plantain polysaccharides.

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