AbstractUterine cancer will claim an estimated 17, 610 lives in the United States in the year 2024. Lack of funding and focus have resulted in little advancement in treatment options for uterine cancer patients. Consequently, uterine cancer incidence and mortality have consistently increased since the 1990’s in the United States. Thus, further investigation and development of uterine cancer therapies is needed. The Peroxiredoxins (I-VI) family of enzymes is responsible for eliminating reactive oxygen species throughout the cell and has been studied in multiple organisms and diseases, including cancer. The compound 2, 3-bis(bromomethyl)-quinoxaline 1, 4-dioxide (Conoidin A) is a Peroxiredoxin II inhibitor that has been studied in the parasite, Toxoplasma gondii. It inhibits the enzymatic activity of Peroxiredoxin II when studied in vitro by covalently binding to cysteine. Recent reports identify Peroxiredoxin II as a potential therapeutic target for cancer therapies and indicate that Peroxiredoxin II down-regulation promotes cancer cell death. Thus, the purpose of these studies was to evaluate Conoidin A as a potential therapeutic for uterine cancer. Here, we report that concentrations of 100 μM, 75 μM, and 50 μM of Conoidin A decreased growth of the uterine cancer cell line, HEC-1-A, after 24 hours as measured using crystal violet assays. Conoidin A concentrations of 100 μM, 75 μM, and 50 μM compromised anchorage-independent growth of HEC-1-A cells in soft agar assays. Furthermore, p53 up-regulation (p53+) correlates with poor prognosis in uterine cancer patients. To determine if Conoidin A is capable of decreasing growth of p53+ tumors, increasing Conoidin A concentrations were tested on the p53+ cell line, C-33a, using crystal violet assays. Preliminary studies found Conoidin A abolishes C-33a growth at concentrations of 100 μM, 75 μM, and 50 μM after 24 hours of treatment. These data identify Conoidin A as a potential therapeutic for uterine cancer, including p53+ tumors. Furthermore, these studies establish Peroxiredoxin II as a novel therapeutic target for this disease.Citation Format:Kaitlyn Mayo, Kennedy Szabo, Calli A. Davison-Versagli. Anticancer effects of 2, 3-bis(bromomethyl)-quinoxaline 1, 4-dioxide on uterine cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5710.

21 Apr 2025·Cancer Research

Abstract 16: Differential stemness properties in bone marrow-derived mesenchymal stem cells from healthy subjects and from patients with acute myeloid leukemia

Author: El-Sabban, Marwan ; Ismail, Souraya ; Al Feghali, Fouad ; Deleuze-Masquéfa, Carine ; El Hajj, Hiba ; Abdel-Samad, Rana ; Bonnet, Pierre-Antoine ; Saliba, Jessica ; Shaito, Abdullah A.

AbstractStudy purpose:The imidazoquinoxaline EAPB0503, an imiquimod analogue, exhibits immunomodulatory and anti-cancer properties against several blood malignancies, including acute myeloid leukemia (AML). The bone marrow (BM) niche plays a pivotal role in normal hematopoiesis and in leukemogenesis. To characterize the molecular potency of EAPB0503 in AML, we compared its effect on the expression profile of genes involved in the function and differentiation potential of BM-derived mesenchymal stem cells (BM-MSCs) from a healthy subject and a patient with AML.Experimental procedures:Transcriptional levels of stemness markers and genes potentially relevant to niche function were evaluated by quantitative real-time polymerase chain reaction in BM-MSCs isolated from BM aspirates of subjects undergoing BM analysis and exposed to EAPB0503. Differentiation potential was assessed in BM-MSCs exposed to EAPB0503 and induced into osteogenic differentiation using a mixture of dexamethasone, ascorbic acid and β-glycerophosphate (DAG). A colorimetric assay was used to detect early-stage osteogenic differentiation by evaluating alkaline phosphatase (ALP) activity.Summary of results:EAPB0503 treatment induced a differential expression of functionally important marker genes between BM-MSCs from the healthy subject and the patient with AML. As such, levels of Connexin 43 (GJA1) decreased in healthy BM-MSCs and increased in AML-derived BM-MSCs following treatment with EAPB0503. In contrast, transcriptional levels of multi-drug resistance 1 (MDR1 or ABCB1) markedly increased in healthy BM-MSCs and remained stable in AML-derived BM-MSCs. Vascular Endothelial Growth Factor (VEGF) and N-cadherin (CDH2) transcriptional levels increased in AML-derived BM-MSCs, with modest changes in healthy MSCs. In addition, AML-derived BM-MSCs do not seem to respond to differentiation signals in a manner similar to healthy BM-MSCs, as shown by ALP activity.Conclusions:These preliminary findings underscore the differential transcriptional profile in BM-MSCs derived from a healthy subject or a patient with AML. Importantly, a differential gene expression profile was also obtained in response to the therapeutic drug EAPB0503. Our preliminary findings implicate the BM niche in AML leukemogenesis and response to drugs.Citation Format:Souraya Ismail, Fouad Al Feghali, Rana Abdel-Samad, Abdullah A. Shaito, Hiba El Hajj, Carine Deleuze-Masquéfa, Pierre-Antoine Bonnet, Marwan El-Sabban, Jessica Saliba. Differential stemness properties in bone marrow-derived mesenchymal stem cells from healthy subjects and from patients with acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 16.

01 Apr 2025·Proceedings of the Royal Society B: Biological Sciences

Cranial kinematics and prey-type effects in Amia ocellicauda feeding strikes

Article

Author: Whitlow, Katrina R. ; Westneat, Mark W. ; Ross, Callum F.

Variability in the biomechanics and kinematics of prey capture in vertebrates has been studied extensively, with evidence of multiple strategies for successful feeding in many taxa. Early research into suction-feeding strikes in fishes hypothesized that fish utilize a set of pre-programmed strike kinematics that cannot be altered once initiated. However, more recent evidence has demonstrated that teleost fishes not only deploy unique strike kinematics for different prey types, but they also alter their kinematics in response to a prey item attempting to escape. It has not yet been explicitly investigated whether non-teleost actinopterygians can also modulate the strike in response to different prey types. Here, we examined the kinematics of suction strikes in bowfin, Amia ocellicauda , a holostean fish most closely related to gars. We recorded Amia feeding on both feeder fish and worms, two types of live prey differing in evasiveness, using X-ray reconstruction of moving morphology. We found significant prey-type effects on the magnitude, timing and velocity of jaw opening, hyoid arch depression and pectoral girdle motions. These prey-type effects demonstrate that the ability to modulate feeding strikes evolved early in actinopterygian fishes and is possibly the ancestral state for jawed vertebrates.

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