Eradication of Therapy-Resistant Cancer Stem Cells by Novel Telmisartan Derivatives DOI Creative Commons
Anna M. Schoepf, Mathias Gebhart, Mark J. Federspiel

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 18, 2024

The present structure–activity relationship study investigates the development of novel chemosensitizers targeting therapy-resistant cancer stem cells (CSCs). We used 4′-((2-propyl-1H-benzo[d]imidazole-1-yl)methyl)-[1,1′-biphenyl]-2-carboxylic acid, derived from angiotensin II type 1 receptor blocker telmisartan, as a lead structure, demonstrating that biphenyl moiety is essential for chemosensitizing activity. Introducing methyl carboxylate or carboxamide instead COOH-group significantly enhanced this effect, leading to highly potent compounds. These novel, noncytotoxic effectively target CSCs and overcome drug resistance by interfering with CSC persistence mechanisms─hyperactivated STAT5 signaling increased transporter activity─with demonstrated efficacy in leukemia, ovarian, prostate cancers. telmisartan (telmi-amide, 7c) reduced tumor growth an imatinib-resistant leukemia xenograft model, both monotherapy combined imatinib, showing promising oral bioavailability tolerability. In summary, derivatives act effective offer innovative strategy various malignant diseases.

Language: Английский

The Role of Chronic Inflammation in Pediatric Cancer DOI Open Access

Christine Mella,

Panogiotis Tsarouhas,

Maximillian Brockwell

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(1), P. 154 - 154

Published: Jan. 6, 2025

Inflammation plays a crucial role in wound healing and the host immune response following pathogenic invasion. However, unresolved chronic inflammation can result tissue fibrosis genetic alterations that contribute to pathogenesis of human diseases such as cancer. Recent scientific advancements exploring underlying mechanisms malignant cellular transformations cancer progression have exposed significant disparities between pediatric adult-onset cancers. For instance, cancers tend lower mutational burdens arise actively developing tissues, where cell-cycle dysregulation leads gene, chromosomal, fusion gene development not seen counterparts. As such, findings adult cannot be directly applied cancers, unique mutations inherent etiologies remain poorly understood. Here, we review processes chromosomal instability, tumor microenvironment, tumorigenesis transformation explore current therapeutic interventions maintain and/or restore inflammatory homeostasis.

Language: Английский

Citations

2
Hyaluronic Acid-Based Drug Delivery Systems for Cancer Therapy DOI Creative Commons
Ekaterina Pashkina, М. В. Быкова,

M. T. Berishvili

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 61 - 61

Published: Jan. 7, 2025

In recent years, hyaluronic acid (HA) has attracted increasing attention as a promising biomaterial for the development of drug delivery systems. Due to its unique properties, such high biocompatibility, low toxicity, and modifiability, HA is becoming basis creation targeted systems, especially in field oncology. Receptors overexpressed subpopulations cancer cells, one them, CD44, recognized molecular marker stem cells. This review examines role receptors health tumors analyzes existing HA-based systems their use various types cancer. The new will bring opportunities challenges anti-cancer therapy.

Language: Английский

Citations

1
Recent advances in targeting cancer stem cells by using nanomaterials DOI
Vahid Rahimkhoei, Ali Akbari,

Amar Yasser Jassim

et al.

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 125381 - 125381

Published: Feb. 1, 2025

Language: Английский

Citations

1
A Distinct Alternative mRNA Splicing Profile Identifies the Oncogenic CD44 Transcript Variant 3 in KMT2A-Rearranged Pediatric T-cell Acute Lymphoblastic Leukemia Cells DOI Creative Commons

Amanda Ramilo Amor,

Sabina Enlund,

Indranil Sinha

et al.

Experimental Hematology, Journal Year: 2025, Volume and Issue: unknown, P. 104712 - 104712

Published: Jan. 1, 2025

Language: Английский

Citations

0
Meningeal leukaemic aggregates as foci of cell expansion and chemoresistance in acute lymphoblastic leukaemia metastasis DOI Creative Commons

Paula Ortiz-Sánchez,

Sara González-Soto,

Luz H Villamizar

et al.

Cellular Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Language: Английский

Citations

0
The R-RAS2 GTPase is a signaling hub in triple-negative breast cancer cell metabolism and metastatic behavior DOI Creative Commons
Claudia Cifuentes,

Lydia Horndler,

P. Grosso

et al.

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: April 12, 2025

Recent research from our group has shown that the overexpression of wild-type RAS-family GTPase RRAS2 drives onset triple-negative breast cancer (TNBC) in mice following one or more pregnancies. This phenomenon mirrors human TNBC, where is overexpressed approximately 75% cases, particularly tumors associated with postpartum period. These findings underscore relevance R-RAS2 TNBC development and progression. We conducted RNA sequencing on derived conditional knock-in overexpressing to identify somatic mutation landscape these mice. Additionally, we developed a cell line RRAS2-overexpressing mice, enabling loss-of-function studies investigate role various pathobiological parameters cells, including migration, invasiveness, metabolic activity, metastatic spread. Furthermore, proteomic analysis freshly isolated tumor identified plasma membrane receptors interacting R-RAS2. Our demonstrate driven by exhibits pattern mutations similar those observed cancer, genes involved stemness, extracellular matrix interactions, actin cytoskeleton regulation. Proteomic revealed interacts 245 membrane-associated proteins, key solute carriers metabolism (CD98/LAT1, GLUT1, basigin), adhesion interaction proteins (CD44, EpCAM, MCAM, ICAM1, integrin-α6, integrin-β1), stem markers (β1-catenin, α1-catenin, PTK7, CD44). show regulates CD98/LAT1 transporter-mediated mTOR pathway activation mediates CD44-dependent migration invasion, thus providing mechanism which promotes metastasis. associates CD44, CD98/LAT1, other regulate reorganization, distant metastasis formation TNBC. establish as central driver malignancy highlight its potential promising therapeutic target, aggressive, postpartum-associated cancers.

Language: Английский

Citations

0
Establishment of fracture blister model and analysis of plasma protein markers in rats DOI Creative Commons
Xin Hu, Peiyuan Wang, Tao Wang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 14, 2025

Purpose Fracture blister (FB) is a frequent complication in orthopedic surgery. The primary objective of this study was to refine the animal model FB and identify plasma protein markers associated with its development progression. Methods In study, Sprague-Dawley (SD) rats were used as experimental subjects. Various pressures compression durations applied lower limbs fractures compare differential expression patterns (DEPs) between pressure-time combination that resulted highest incidence blisters other groups. Subsequently, we investigated variations DEPs across different time intervals established model. Results Our findings indicate following limb fracture SD rats, formation observed under conditions 450 mmHg pressure 9 hours (46%, 7/15). group, levels CD44 B2M significantly elevated, while those Activin R2A reduced. Furthermore, temporal profile group found CXCL16 ROBO1 reached peak secretion 48 post-injury, followed by subsequent decline. Additionally, IL-2RG IL-7 continued increase after injury. Conclusions decrease might be potential influencing factors for higher blisters. their end molding, IL-2 RG R which will provide new direction occurrence mechanism

Language: Английский

Citations

0
Development and Characterization of CD44-Targeted X-Aptamers with Enhanced Binding Affinity for Cancer Therapeutics DOI Creative Commons
Hongyu Wang,

Weiguo He,

Miguel-Angel Elizondo-Riojas

et al.

Bioengineering, Journal Year: 2025, Volume and Issue: 12(2), P. 113 - 113

Published: Jan. 26, 2025

CD44, a pivotal cell surface molecule, plays crucial role in many cellular functions, including cell-cell interactions, adhesion, and migration. It serves as receptor for hyaluronic acid is involved lymphocyte activation, recirculation, homing, hematopoiesis. Moreover, CD44 commonly used cancer stem marker associated with tumor progression metastasis. The development of aptamers that specifically target can be utilized to CD44-positive cells, drug delivery. Building on the primary sequences our previously selected thioaptamers (TAs) observed variations, we developed bead-based X-aptamer (XA) library by conjugating drug-like ligands (X) 5-positions certain uridines complete monothioate backbone. From this, an XA high affinity binding domain (HABD) from large combinatorial modified N-acetyl-2,3-dehydro-2-deoxyneuraminic (ADDA). This demonstrated enhanced protein up 23-fold. X-aptamers (both amine form ADDA form) also showed CD44-overexpressing human ovarian IGROV cells. Secondary structure predictions using MFold identified several motifs smaller constructs various stem-loop regions. Among motifs, motif 3 5 cells form, compared affinities scrambled sequence. effect enhancer was not uniform within aptamer, highlighting importance optimal ligand positioning. incorporation only broadened XA’s chemical diversity but increased area, offering specificity. Therefore, strategic use site-directed modifications allows fine-tuning aptamer properties offers flexible, generalizable framework developing high-performance wide range molecules.

Language: Английский

Citations

0
Diagnostic Potential of CD44, CD133, and VDR in Epithelial Ovarian Tumors: Association with Histopathology Parameters DOI Open Access
Ljubiša Jovanović, Branka Šošić‐Jurjević, Andja Ćirković

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3729 - 3729

Published: April 15, 2025

Cancer stem cells (CSCs) significantly contribute to heterogeneity, malignancy, and therapy resistance in ovarian cancer. Recent studies emphasize the role of vitamin D receptor (VDR) regulating cell differentiation stemness various types This study aims determine expression levels CD44, CD133, VDR epithelial tumors (EOTs) compare these across different tumor types, including benign, atypical proliferative tumors, five malignant phenotypes, order evaluate their potential as diagnostic tools for malignancy. Tissue samples from 218 patients diagnosed with EOT were analyzed. Clinical histopathologic parameters recorded. Quantitative immunohistochemical tissue microarray analysis was used assess using two scoring systems. Comparisons made between benign (n = 45), 42), carcinomas 131), high-grade serous (HGSC) non-HGSC subtypes. Ovarian cancer, especially HGSC, showed a higher CD44 (p < 0.05) compared tumors. The CD133 highest 0.05). A moderate positive correlation found all groups, significant correlations grade FIGO stage cancer increased aggressive along elevated highlights complexity biology. These markers may serve valuable targets diagnosis

Language: Английский

Citations

0
Podoplanin depletion in tonsil-derived mesenchymal stem cells induces cellular senescence via regulation of the p16Ink4a/Rb pathway DOI Creative Commons
Ha Yeong Kim, Han Su Kim

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 12, 2024

Mesenchymal stem cells (MSCs) are widely used in the development of therapeutic tools regenerative medicine. However, their quality decreases during vitro expansion because heterogeneity and acquired cellular senescence. We investigated potential role podoplanin (PDPN) minimizing senescence maintaining stemness tonsil-derived MSCs (TMSCs).

Language: Английский

Citations

1