Integrated Analysis of Single-Cell and Bulk RNA Sequencing Reveals HSD3B7 as a Prognostic Biomarker and Potential Therapeutic Target in ccRCC DOI Open Access

Guicen Liu,

Qichen Liu, Jiawei Zhao

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 12929 - 12929

Опубликована: Дек. 1, 2024

Clear cell renal carcinoma (ccRCC) is the most common kidney malignancy, with a poor prognosis for advanced-stage patients. Identifying key biomarkers involved in tumor progression crucial improving treatment outcomes. In this study, we employed an integrated approach combining single-cell RNA sequencing (scRNA-seq) and bulk (bulk RNA-seq) to identify associated ccRCC prognosis. Single-cell transcriptomic data were obtained from publicly available datasets, genes related screened using Monocle2. Bulk RNA-seq retrieved The Cancer Genome Atlas (TCGA) scRNA-seq explore heterogeneity. We identified 3 beta-hydroxy steroid dehydrogenase type 7 (HSD3B7) as candidate biomarker ccRCC, overall survival, disease-specific progression-free interval. Elevated HSD3B7 expression correlated aggressive clinical features such advanced TNM stages, histologic grades, metastasis. Functional studies demonstrated that promotes proliferation, migration, invasion vitro, while its silencing significantly inhibits growth vivo. Our findings reveal novel providing insights into role potential target therapy. This study highlights value of integrating uncover regulators biology lays foundation developing personalized therapeutic strategies

Язык: Английский

Development and Preclinical Evaluation of [64Cu]Cu-NOTA-ABDB6: A CD70 and Albumin Dual-Binding Tracer with Improved Pharmacokinetics DOI
Xiaoyan Li, You Zhang, Jason C. Mixdorf

и другие.

Journal of Nuclear Medicine, Год журнала: 2025, Номер unknown, С. jnumed.124.268835 - jnumed.124.268835

Опубликована: Фев. 27, 2025

CD70 is an emerging biomarker for both solid tumors and hematologic malignancies, highlighting the urgent need a molecular imaging tracer capable of visualizing with favorable pharmacokinetics. Methods: ABDB6 was prepared by fusing albumin-binding domain ABD035 CD70-targeting single-domain antibody RCCB6, which we previously reported. The resulting then conjugated to bifunctional chelator p-SCN-NOTA labeled 64Cu produce [64Cu]Cu-NOTA-ABDB6. Flow cytometry used screen 6 lymphoma cell lines varying expression levels. Cell uptake in vivo immuno-PET studies were conducted fully evaluate pharmacokinetic properties tumor-targeting efficacy An blocking study performed validate targeting specificity [64Cu]Cu-NOTA-ABDB6, followed immunohistochemistry fluorescent immunostaining correlate expression. Results: labeling achieved high radiochemical yield specific activity. Significant observed 5 (TMD8, HBL1, OCI-LY10, LCL-EBV, type III latency Burkitt [BL] cells) but not I BL cells, served as negative control. [64Cu]Cu-NOTA-ABDB6 exhibited good affinity protein at nanomolar level (inhibitory concentration 50%, 91.57 nM) binding human CD70. Immuno-PET demonstrated excellent tumor retention various CD70-positive models BL, LCL-EBV), highest values recorded 24.67 ± 1.36, 18.02 4.29, 14.68 1.20 percentage injected dose per gram tissue (%ID/g) 48 h after injection, respectively. These significantly higher than that CD70-negative tumor, had 3.59 0.28 %ID/g same scanning time point (P < 0.05). In TMD8 group, 5.99 lower control group 0.01). Both biodistribution histology results corroborated these findings. Conclusion: effectively visualized levels different models. Its clinical potential may provide insights into patients.

Язык: Английский

Процитировано

0

Synthesis and preclinical evaluation of an Al18F radio-fluorinated bivalent PD-L1 nanobody DOI
Yong Huang,

Dongye Zheng,

Chengze Li

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 289, С. 117487 - 117487

Опубликована: Март 7, 2025

Язык: Английский

Процитировано

0

CD70-targeted cancer theranostics: Progress and challenges DOI
Weijun Wei, Viktor Grünwald,

Ken Herrmann

и другие.

Med, Год журнала: 2025, Номер unknown, С. 100671 - 100671

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0

CD70-Targeted [18F]RCCB6 Immuno-PET/CT Imaging in Patients with Nasopharyngeal Carcinoma: A Proof-of-Concept Study DOI
Bing‐Jun Shi, You Zhang, Shuo Wu

и другие.

Journal of Nuclear Medicine, Год журнала: 2025, Номер 66(6), С. 865 - 872

Опубликована: Апрель 30, 2025

CD70 has emerged as a promising biomarker for nasopharyngeal carcinoma (NPC). This study investigated expression patterns in NPC specimens and evaluated the diagnostic potential of CD70-targeted [18F]RCCB6 immuno-PET/CT patients with NPC. Methods: was analyzed 80 archived correlated clinical pathologic features. Using [18F]RCCB6, single-domain antibody-derived tracer specific human CD70, efficacy assessed 25 compared that 18F-FDG PET/CT. Results: positively expressed 72 (90%) specimens, levels strongly Epstein-Barr virus (EBV) titers (rs = 0.437; P < 0.001) N-staging (P 0.006). In all 15 early-stage NPC, achieved 100% detection rate primary tumor 93% (75/81) local lymph node metastasis. uptake well expression. head-to-head comparison, demonstrated higher sensitivity than did detecting metastasis (100% [58/58] vs. 90% [52/58], respectively; 0.031), equivalent abilities lesions most distant metastases (100%). Notably, better evaluation skull-base invasion clear border bone metastases, indicated by its (7.25 5.95; 0.025). Conclusion: is potent provides precise mapping enhances diagnosis primary, metastatic, recurrent NPCs, outperforming metastases.

Язык: Английский

Процитировано

0

Development of [18F]AlF-RESCA-H006 as a Novel Molecular Probe for 5T4 Tumor Imaging and Exploration of Its Application in Pancreatic Adenocarcinoma DOI

Jinping Kong,

Huixia Zhang,

Ruhua Tian

и другие.

Molecular Pharmaceutics, Год журнала: 2025, Номер unknown

Опубликована: Май 30, 2025

Pancreatic adenocarcinoma (PAAD) is an extremely lethal cancer, making early detection and precise staging essential for extending survival. Upregulation of 5T4 mRNA was detected in bioinformatics analysis using data from the Cancer Genome Atlas Genotype-Tissue Expression. In current work, we confirmed overexpression protein tumor samples PAAD compared with corresponding paraneoplastic tissue. To visualize via positron emission tomography (PET) noninvasively, successfully developed [18F]AlF-RESCA-H006 based on a single-domain antibody fragment. The radiotracer demonstrated high binding affinity toward antigens vitro remained stable final formulation up to 4 h storage at room temperature. two preclinical mouse models pancreatic clearly identified sites, showing radioactivity accumulation 2.43 ± 0.46% ID/g Balb/C mice BxPC-3 xenografts 2.88 1.02% NCG PANC-1 xenografts. Taken together, promising PET tracer detecting antigen alteration PAAD. Further investigations are required assess its defluorination level higher species permeability through dense extracellular matrix cancer.

Язык: Английский

Процитировано

0

Biological characterization of renal masses using immuno-PET DOI Creative Commons
Fabrizia Gelardi, Alessandro Larcher, Lidija Antunovic

и другие.

European Journal of Nuclear Medicine and Molecular Imaging, Год журнала: 2024, Номер 51(8), С. 2442 - 2443

Опубликована: Май 11, 2024

Язык: Английский

Процитировано

2

Advancements in Nuclear Imaging Using radiolabeled Nanobody tracers to support Cancer Immunotherapy DOI Creative Commons
Katty Zeven, Yoline Lauwers, Lynn De Mey

и другие.

Immunotherapy Advances, Год журнала: 2024, Номер 4(1)

Опубликована: Янв. 1, 2024

The evolving landscape of cancer immunotherapy has revolutionized treatment. However, the dynamic tumor microenvironment led to variable clinical outcomes, indicating a need for predictive biomarkers. Noninvasive nuclear imaging, using radiolabeled modalities, aided in patient selection and monitoring their treatment response. This approach holds promise improving diagnostic accuracy, providing more personalized regimen, enhancing Nanobodies or single-domain antibodies, derived from camelid heavy-chain allow early timepoint detection targets with high target-to-background ratios. To date, plethora nanobodies have been developed imaging tumor-specific antigens, immune checkpoints, cells, both at preclinical level. review comprehensively outlines recent advancements nanobody-based on levels. Additionally, impact expected future use radiopharmaceuticals supporting diagnosis follow-up are discussed.

Язык: Английский

Процитировано

2

Trends in cancer imaging DOI
Xinyuan Zhou,

Binyu Shi,

Gang Huang

и другие.

Trends in cancer, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

2

Immuno-PET/CT Imaging of Trop2 with [18F]AlF-RESCA-T4 Differentiates Lung Cancer from Inflammation DOI
Wei Huang, Min Cao, Yanfei Wu

и другие.

Journal of Nuclear Medicine, Год журнала: 2024, Номер unknown, С. jnumed.124.268751 - jnumed.124.268751

Опубликована: Ноя. 14, 2024

Immuno-PET/CT imaging, a branch of molecular can noninvasively and specifically visualize biomarker expression across the body. Trophoblast cell surface antigen 2 (Trop2) is pan-cancer plays crucial role in tumorigenesis through multiple signaling pathways. The study aims to develop translate novel Trop2 single-domain antibody (sdAb) tracers for clinical use. Methods: Two sdAbs (i.e., His-tagged T4 His-tag−free RT4) are recombinantly expressed Chinese hamster ovary cells. purities binding kinetics determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, high-performance liquid chromatography, plasmon resonance assays. AlF restrained complexing agent (RESCA) method applied 18F-labeled sdAb ([18F]AlF-RESCA-T4 [18F]AlF-RESCA-RT4), followed thorough preclinical imaging blocking studies on tumor-bearing mice pilot trial evaluating safety feasibility [18F]AlF-RESCA-T4 immuno-PET/CT. Results: [18F]AlF-RESCA-RT4 possess high radiochemical purities. Preclinical T3M-4 tumor model revealed prominent uptake (percentage injected dose/g) (11.13 ± 1.53, n = 4) (8.83 1.22, 4), which were significantly reduced coinjection unlabeled RT4 studies. His-tag removal strategy further optimized probe's in vivo pharmacokinetics renal radioactivity accumulation without decreasing uptake. In trial, immuno-PET/CT showed promising potency annotating differentiating tumors from inflammatory diseases such as tuberculosis. Conclusion: annotate expression. Clinical screen patients Trop2-targeted therapies differentiate lung inflammation cancer.

Язык: Английский

Процитировано

1

[18F]RCCB6 immunoPET/CT detects primary clear cell renal cell carcinoma DOI
Shuo Wu,

Qianyun Wu,

Jianjun Liu

и другие.

European Journal of Nuclear Medicine and Molecular Imaging, Год журнала: 2024, Номер unknown

Опубликована: Дек. 7, 2024

Процитировано

1