Tumor Cell Lines Research Articles

Proteomic analysis of extracellular vesicles derived from canine mammary tumour cell lines identifies protein signatures specific for disease state

BackgroundCanine mammary tumours (CMT) are among the most common types of tumours in female dogs. Diagnosis currently requires invasive tissue biopsies and histological analysis. Tumour cells shed extracellular vesicles (EVs) containing RNAs and proteins with potential for liquid biopsy diagnostics. We aimed to identify CMT subtype-specific proteome profiles by comparing the proteomes of EVs isolated from epithelial cell lines derived from morphologically normal canine mammary tissue, adenomas, and carcinomas.MethodsWhole-cell protein lysates (WCLs) and EV-lysates were obtained from five canine mammary cell lines: MTH53A (non-neoplastic); ZMTH3 (adenoma); MTH52C (simple carcinoma); 1305, DT1406TB (complex carcinoma); and their proteins identified by LC-MS/MS analyses. Gene Ontology analysis was performed on differentially abundant proteins from each group to identify up- and down-regulated biological processes. To establish CMT subtype-specific proteomic profiles, weighted gene correlation network analysis (WGCNA) was carried out.ResultsWCL and EVs displayed distinct protein abundance signatures while still showing the same increase in adhesion, migration, and motility-related proteins in carcinoma-derived cell lines, and of RNA processing and RNA splicing factors in the adenoma cell line. WGCNA identified CMT stage-specific co-abundant EV proteins, allowing the identification of adenoma and carcinoma EV signatures not seen in WCLs.ConclusionsEVs from CMT cell lines exhibit distinct protein profiles reflecting malignancy state, allowing us to identify potential biomarkers for canine mammary carcinomas, such as biglycan. Our dataset could therefore potentially serve as a basis for the development of a less invasive clinical diagnostic tool for the characterisation of CMT.

New Discorhabdin D Analogues from Latrunculia spp. Sponges.

Chemical profiles of Latrunculia kaakaariki and Latrunculia brevis were investigated, resulting in the isolation of five new discorhabdin D derivatives 1 and 3-6. Their planar structures were solved by combination of NMR and HR-MS, while J-based configurational analysis, computational techniques, and semisynthetic methods were used for the establishment of their absolute configurations. New natural products were tested for their growth inhibitory activity against the NCI-60 human tumor cell line panel, and two compounds 5 and 6 showed low micromolar potency.

Spots on 1H‐Indazole Incorporation into Thiazole Moiety‐Hybrid Heterocycles, Strong Efficacy as Small Molecules with Antimicrobial, Antineoplastic Activity, and In‐Silico Studies

AbstractAmidst the escalating cancer cases and the relentless spread of multidrug‐resistant microbes, the urgency for effective medication is undeniable. In this context, our lab's continuous efforts have led to a promising discovery. We have conducted an extensive study on a series of new heterocycles with an indazolylthiazole component, which holds great promise as antimicrobial and anticancer drugs. The bioactivity tests, conducted with meticulous methodology, have demonstrated that the synthesized compounds possess remarkable antibacterial activity against various pathogenic strains. In a controlled lab setting, we have observed that derivatives 9, 11, and 12a effectively induce apoptosis in HCT‐166 and Huh‐7 (liver carcinoma) cell lines. Among these, derivative 11 has shown the highest selectivity (SI=14.54±1.2 and 16.51±1.4) and the lowest IC50 value. These compounds also exhibit broad‐spectrum antimicrobial activity. The anticancer activity of the synthesized compounds has been computationally confirmed through molecular modeling using MOE software and pharmacokinetic studies. Most of the tested compounds have shown significant cytotoxic activity against tumor cell lines, with high safety against normal human cells, thereby paving the way for a hopeful and promising future of antimicrobial and anticancer drugs, with potential applications in [specific_application_1] and [specific_application_2].

Potassium Benzoate Induced Cytotoxicity via Alteration of Gene Expression-Associated Apoptosis and Cell Cycle Genes in Tumor Cell Lines

Potassium Benzoate Induced Cytotoxicity via Alteration of Gene Expression-Associated Apoptosis and Cell Cycle Genes in Tumor Cell Lines

Exploring the Antitumor Potential of New Indazole-indolizines Designed by Molecular Hybridization

Background: Cancer represents the major health problem faced by the population of the world, remaining one of the main causes of death. Hence, the development of new targeted antitumor drugs with high efficacy and lower toxicity is still needed. Objective: As a continuation of our work to discover new molecules with cytotoxic properties, two heterocyclic scaffolds, namely indolizine, and indazole, were combined in the same molecule, aiming to improve the bioactivity. This article focused on the synthesis, characterization, and biological evaluation of a series of new indazole-indolizine hybrid compounds. Methods: The biological potential of the synthesized compound was investigated in vitro against the human farnesyltransferase enzyme and NCI 60 tumor cell lines panel. While the farnesyltransferase inhibitory activity was modest, a very good antiproliferative action was observed for compound 4a, which, at a concentration of 10 μM, inhibited the growth of 20 types of cancer cells by more than 50% and showed cytotoxic action against the ovarian cancer cell line OVCAR-4. Results: A series of novel indazole-indolizine hybrids were synthesized via a [3+2] cycloaddition reaction, fully characterized and biologically evaluated for antitumor potential. Conclusion: Compound 4a could be a promising starting point in the development of new antitumoral agents. Further biological investigations will be performed to identify the biological target of the compounds. Moreover, different synthetic strategies to introduce new substituents on the indolizine core will be addressed.

Biosourced Au(III) Complexes from D-Xylose: Synthesis and Biological Evaluation.

A series of xylose-based ligands was obtained using a convenient approach, in a few steps from D-xylose. The complexation properties of these ligands towards Au3+ cations have been studied through different methods (multinuclear NMR, mass spectrometry, elemental analysis). The biological properties (antibacterial and anti-tumoral) of all the isolated xyloside Au(III) complexes were investigated in vitro. The xyloside Au(III) complexes gave the highest activities against E. coli(vs P. aeruginosa, S. aureus and S. epidermidis). The study also revealed that the nature of the sugar may play an important role in determining the selectivity of the antibacterial effect. Preliminary anti-tumoral evaluations showed that one complex containing a polyamine chain, exhibited interesting anti-proliferative activities on breast tumor cell lines MDA-MB-231 and BT-20. The anti-migratory effect of this complex also showed an average 35% reduction in cell migration on the same two cancer cell lines.

Development and extensive sequencing of a broadly-consented Genome in a Bottle matched tumor-normal pair.

The Genome in a Bottle Consortium (GIAB), hosted by the National Institute of Standards and Technology (NIST), is developing new matched tumor-normal samples, the first to be explicitly consented for public dissemination of genomic data and cell lines. Here, we describe a comprehensive genomic dataset from the first individual, HG008, including DNA from an adherent, epithelial-like pancreatic ductal adenocarcinoma (PDAC) tumor cell line and matched normal cells from duodenal and pancreatic tissues. Data for the tumor-normal matched samples comes from thirteen distinct state-of-the-art whole genome measurement technologies, including high depth short and long-read bulk whole genome sequencing (WGS), single cell WGS, and Hi-C, and karyotyping. These data will be used by the GIAB Consortium to develop matched tumor-normal benchmarks for somatic variant detection. We expect these data to facilitate innovation for whole genome measurement technologies, de novo assembly of tumor and normal genomes, and bioinformatic tools to identify small and structural somatic mutations. This first-of-its-kind broadly consented open-access resource will facilitate further understanding of sequencing methods used for cancer biology.

Oncolytic Coxsackievirus B3 Strain PD-H Is Effective Against a Broad Spectrum of Pancreatic Cancer Cell Lines and Induces a Growth Delay in Pancreatic KPC Cell Tumors In Vivo

Pancreatic cancer is one of the deadliest cancers globally, with limited success from existing therapies, including chemotherapies and immunotherapies like checkpoint inhibitors for patients with advanced pancreatic ductal adenocarcinoma (PDAC). A promising new approach is the use of oncolytic viruses (OV), a form of immunotherapy that has been demonstrated clinical effectiveness in various cancers. Here we investigated the potential of the oncolytic coxsackievirus B3 strain (CVB3) PD-H as a new treatment for pancreatic cancer. In vitro, PD-H exhibited robust replication, as measured by plaque assays, and potent lytic activity, as assessed by XTT assays, in most pancreatic tumor cell lines, outperforming two other coxsackievirus strains tested, H3N-375/1TS and CVA21. Thus, H3N-375/1TS showed efficient replication and lytic efficiency in distinctly fewer tumor cell lines, while most tumor cells were resistant to CVA21. The oncolytic efficiency of the three OV largely correlated with mRNA expression levels of viral receptors and their ability to induce apoptosis, as measured by cleaved caspase 3/7 activity in the tumor cells. In a syngeneic mouse model with subcutaneous pancreatic tumors, intratumoral administration of PD-H significantly inhibited tumor growth but did not completely stop tumor progression. Importantly, no virus-related side effects were observed. Although pancreatic tumors respond to PD-H treatment, its therapeutic efficacy is limited. Combining PD-H with other treatments, such as those aiming at reducing the desmoplastic stroma which impedes viral infection and spread within the tumor, may enhance its efficacy.

Abstract A033: Pro-inflammatory tumor cells drive CD4+ T cell localization within heterogeneous tumors

Abstract Immunotherapies such as immune checkpoint inhibitors (ICIs) have greatly improved patient outcomes in multiple tumor types, but ICIs have failed to achieve responses in many patients. Meta-analyses of patient cohorts treated with ICIs have observed that worse clinical outcomes are strongly correlated with high levels of intratumoral genetic heterogeneity (ITH). ITH occurs when tumor cells mutate as they divide, typically due to oxidative stress or DNA damage from rapid proliferation and continued carcinogenic insults, generating tumor subclones. However, the mechanisms by which ITH impairs the anti-tumor immune response are not fully understood. We propose a novel mechanism for how ITH in highly T cell-infiltrated inflamed tumors can adversely affect T cell behavior. We hypothesize that strongly pro-inflammatory tumor subclones secreting robust pro-inflammatory chemokine profiles can dominate T cell trafficking within the tumor, resulting in a weakened immune response against other tumor subclones. Using a murine squamous cell skin carcinoma (SCC) model, we have demonstrated that in immune-inflamed tumors, the spatial distribution and behavior of tumor-infiltrating T cells is influenced by ITH. A strongly pro-inflammatory tumor line expressing an endogenous RFP fluorophore was mixed with a weakly pro-inflammatory tumor line expressing an endogenous YFP fluorophore at a 1:1 ratio. The resulting tumors contained distinct RFP+ and YFP+ regions. These were analyzed by immunofluorescence (IF) and by manually dissecting the tumors and analyzing each region by flow cytometry. Flow cytometry analysis determined that the strongly pro-inflammatory RFP+ regions contained significantly more total T cells and CD4+ T cells than YFP+ regions. Furthermore, FoxP3- “conventional” CD4+ T cells were significantly more likely to be “terminal effector-like” CD44+CD62L- in RFP+ regions, and significantly more likely to be “naïve-like” CD62L+CD44- in YFP+ regions. IF analysis confirmed the preferential distribution of CD4+ T cells in RFP+ regions, and observed that this spatial pattern was evident as early as 11 days after subcutaneous injection. Notably, this localization trend did not occur with CD8+ T cells, which were evenly dispersed throughout the tumors. ELISA analysis of lysates of both tumor cell lines determined that the pro-inflammatory RFP+ cell line secretes significantly higher levels of the chemokine CCL5, which has been observed by other studies to selectively mediate CD4+ T cell chemotaxis. These results demonstrate that intratumoral CD4+ trafficking is shaped by the spatial distribution of specific tumor subclones, and suggest tumor cell chemokine signaling may directly mediate T cell spatial localization and behavior within tumors. Citation Format: Robert Letchworth, Savannah Hughes, Abigail Keku, Melissa Reeves. Pro-inflammatory tumor cells drive CD4+ T cell localization within heterogeneous tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A033.

MRNA-seq-based analysis predicts: AEG-1 is a therapeutic target and immunotherapy biomarker for pan-cancer, including OSCC.

The aberrant expression of AEG-1 is significantly correlated with tumorigenesis, development, neurodegeneration and inflammation. However, the relationship between AEG-1 expression and immune infiltration in OSCC, as well as other tumor types, has yet to be comprehensively analyzed. The expression levels, prognostic and clinicopathological characteristics, mutation patterns and methylation landscapes of AEG-1 in various tumors were obtained from multiple databases, including TIMER, GEPIA, HPA, TCGA, UALCAN, cBioPortal, SMART and TISIDB, in addition to single-cell RNA-seq data. The integration of these datasets facilitated the elucidation of the relationships among pan-cancer cellular heterogeneity, immune infiltration and AEG-1 expression levels. In vitro experiments created AEG-1 overexpressing cell lines, and mRNA-seq analyzed AEG-1-related differential genes in OSCC. RT-PCR validated these findings in vivo using xenograft tumors. Tumor cell lines were developed to study AEG-1's effects through H&E, Masson, and PAS staining. Immunohistochemistry examined AEG-1-related gene expression patterns. Our analysis demonstrated that AEG-1 is highly expressed across various cancer types and is associated with tumor grade and patient prognosis. Additionally, AEG-1 amplification was observed in multiple cancers. Notably, we identified a significant elevation of AEG-1 expression in OSCC, which strongly correlated with patient prognosis and immune infiltration. Through mRNA-seq analysis of differentially expressed genes and immune-related gene sets, we identified a strong correlation between AEG-1 and immune infiltration markers such as LCP2, CD247, HLA-DPA1, HLA-DRA, HLA-DRB1, CIITA and CD74 in OSCC. Additionally, AEG-1 was found to regulate Th1/Th2 immune homeostasis, promote glycogen accumulation, and contribute to tumor fibrosis. In conclusion, AEG-1 significantly correlates with prognosis and immune infiltration across various cancer types and holds potential as a novel prognostic immune biomarker for OSCC. This finding may facilitate the identification of patients who are most likely to benefit from adjuvant immunotherapy.

The Effects of Crude Alkaloid Extracts of Convolutes Arvensis on Tumour Cell Lines and Their Potential For Toxicity

General Background: Cancer remains a leading cause of mortality worldwide, and the search for effective treatments continues to intensify. Specific Background: Convolvulus arvensis has been traditionally used for medicinal purposes, but its potential as an anticancer agent is underexplored. Knowledge Gap: The cytotoxic and apoptotic mechanisms of crude alkaloids extracted from C. arvensis against specific cancer cell lines have not been fully characterized. Aims: This study investigates the antioxidant activity and cytotoxic effects of C. arvensis crude alkaloids on mouse liver cancer (HC) and human breast cancer (AMJ13) cell lines, focusing on apoptosis-related gene expression. Results: The antioxidant activity of C. arvensis was comparable to that of ascorbic acid, with inhibition rates of 92.01% at 500 µg/ml. Crude alkaloids demonstrated dose-dependent cytotoxicity, with a maximum inhibition rate of 82.65% in AMJ13 cells and 79.49% in HC cells at 500 µg/ml. Gene expression analysis revealed upregulation of caspase-9, indicating apoptosis via the intrinsic mitochondrial pathway. Novelty: This study is among the first to provide molecular evidence of C. arvensis-induced apoptosis through the intrinsic pathway, offering a novel insight into its anticancer potential. Implications: These findings suggest that C. arvensis alkaloids could be developed as a therapeutic option for cancer treatment, with future studies needed to isolate specific compounds and assess their in vivo efficacy. Highlights: C. arvensis alkaloids show antioxidant activity similar to ascorbic acid. Alkaloids inhibit liver and breast cancer cell growth dose-dependently. Apoptosis triggered via caspase-9 through the mitochondrial pathway. Keywords: Convolvulus arvensis, alkaloids, cancer, apoptosis, antioxidant

Dynamic reciprocal interactions between activated T cells and tumor associated macrophages drive macrophage reprogramming and proinflammatory T cell migration within prostate tumor models

Tumor-associated macrophages (TAMs) have been implicated as a tumor microenvironment (TME) cell population, which may be playing a vital role in the inhibition of effective T cell responses in the prostate TME. In this manuscript, we leverage a novel microscale cell culture platform, known as Stacks, to investigate mono-, co-, and tri-culture TME models comprised of prostate tumor cell lines, primary macrophages, and autologous T cells from patients with prostate cancer. Through multiplexed analysis of these multi-cellular prostate tumor models, we capture a dynamic interaction between primary TAMs and activated T cells that resulted in reciprocal proinflammatory activation of both cell populations upon interaction. These findings suggest that activated T cells are capable of reprogramming immunosuppressive TAMs in the context of prostate tumor models and that TAM reprogramming may play a key supportive role in restoring proinflammatory T cell tumor responses in the prostate TME.

Antitumor activity of PAbs generated by immunization with a novel HER3-targeting protein-based vaccine candidate in preclinical models.

Despite the cumulative evidence supporting HER3 as a target for antitumor therapies, no agents targeting HER3 have been approved for cancer treatment. Most of the agents evaluated in preclinical and clinical trials have been specific monoclonal antibodies (MAbs), with few examples of active immunotherapy directed against this receptor. However, some cancer vaccine formats may generate polyclonal antibodies (PAbs) that replicate the diverse effector mechanisms of MAbs, including ligand neutralization and receptor degradation. In this study, we developed a protein subunit-based monovalent vaccine candidate targeting the extracellular domain (ECD) of HER3. Immunization of mice with a formulation targeting murine ErbB3-ECD successfully overcome tolerance to this self-antigen, inducing high titers of ErbB3-specific PAbs. The antitumor potential of this formulation and the induced PAbs was demonstrated in vivo and in vitro in an ErbB3-overexpressing 3LL-D122-derived tumor model. The immunogenicity of the HER3-ECD-based vaccine candidate was confirmed by the induction of high titers of HER3-specific PAbs. Consistent with the initial results, HER3-ECD-targeting PAbs were cytotoxic in several human epithelial tumor cell lines and exerted antitumor effects in vivo. These results support the value of HER3 as a tumor antigen and the effector mechanisms of HER3-specific therapeutic MAbs, while suggesting the potential of the proposed vaccine candidate for the treatment of HER3-expressing carcinomas.

Endosomal pH, Redox Dual-Sensitive Prodrug Micelles Based on Hyaluronic Acid for Intracellular Camptothecin Delivery and Active Tumor Targeting in Cancer Therapy

Background: CPT is a pentacyclic monoterpene alkaloid with a wide spectrum of antitumor activity. Its clinical application is restricted due to poor water solubility, instability, and high toxicity. We developed a new kind of multifunctional micelles to improve its solubility, reduce the side effecs, and obtain enhanced antitumor effects. Methods: We constructed HA-CPT nano-self-assembly prodrug micelles, which combined the advantages of pH-sensitivity, redox-sensitivity, and active targeting ability to CD44 receptor-overexpressing cancer cells. To synthesize dual sensitive HA-CPT conjugates, CPT was conjugated with HA by pH-sensitive histidine (His) and redox-sensitive 3,3′-dithiodipropionic acid (DTPA). In vitro, we studied the cellular uptake and antitumor effect for tumor cell lines. In vivo, we explored the bio-distribution and antitumor effects of the micelles in HCT 116 tumor bearing nude mice. Results: The dual-sensitive and active targeting HA-His-ss-CPT micelles was proved to be highly efficient in CPT delivery by the in vitro cellular uptake study. The HA-His-ss-CPT micelles escaped from endosomes of tumor cells within 4 h after cellular uptake due to the proton sponge effect of the conjugating His and then quickly released CPT in the cytosol by glutathione (GSH). In mice, HA-His-ss-CPT micelles displayed efficient tumor accumulation and conspicuous inhibition of tumor growth. Conclusions: The novel, dual-sensitive, active targeting nano-prodrug micelles exhibited high efficiency in drug delivery and cancer therapy. This “all in one” drug delivery system can be realized in an ingenious structure and avoid intricate synthesis. This construction strategy can illume the design of nanocarriers responding to endogenous stimuli in tumors.

A Bioengineered Cathepsin B-sensitive Gas Vesicle Nanosystem That Responds With Increased Gray-level Intensity of Ultrasound Biomicroscopic Images

ObjectivesThis work aimed to promote the interaction of a modified Gas Vesicle (GV) with Cathepsin B (CTSB) protease and analyzed their backscattered signal by Ultrasound (US). MethodsWe modified the sequence of the gene coding for GvpC to contain a CTSB cleavage and expressed the protein in an Escherichia coli recombinant system. The protein was purified and added to GVs preparations in which the original GvpC was removed (ΔGV), constituting the modified GV (GV*). Western Blot (WB) test was used to compare GVs with GvpC and engineer GvpC at starting (T0) and after 24 hours (T24) reacting with CTSB. A 21 MHz US B-mode and nonlinear contrast-mode (5% total power) imaged US phantoms having samples of GVwt, ΔGV (stripped GV), GV*, and CTSB+GV*. Also, a 21MHz US B-mode imaged US phantoms having a tumor cell line extracellular fraction (TCEF) and the TCEF+GV* sample. A 100% total US power was applied to collapse the GV structure. ResultsIn WB we detected a decrease in engineered GvpC levels 24 h after the incubation of GV* with CTSB, compared to the concentration at T0, suggesting that CTSB cleaved the engineered GvpC. Regions-of-interest over image of phantom cross-sections were determined and the B-mode image mean gray level intensity resulted in a significant (p<0.05) increase comparing CTSB+GV* with PBS (control), GVwt, ΔGV and GV*. Non-linear mode image gray level intensity from CTSB+GV* increased by 11.79, 7.86 and 14.75 dB from samples containing GVwt, ΔGV and GV*, respectively. GV preparations incubated with TCEF and the TCEF+GV* sample showed an increase of 81% in signal compared to TCEF+GVwt. ConclusionsThe increased ultrasound backscattered signal intensity suggests GVs as a potential biosensor for protease activity, possibly aiding the detection of protease-rich tissue regions.

Targeting the Tumour Antigen 5T4 using CAR-T Cells for the Treatment of Acute Myeloid Leukaemia.

Chimeric antigen receptor (CAR) T cells represent a novel targeted approach to overcome deficits in the ability of the host immune system to detect and eradicate tumours. 5T4 is a tumour-associated antigen expressed on the cell surface of most solid tumours. However, very little is known about its expression in haematological malignancies. Herein, we assess the expression of 5T4 in different types of leukaemias, specifically Acute Myeloid Leukaemia (AML), and normal haematopoietic stem cells (HSCs). We also provide an in vitro assessment of safety and efficacy of 5T4-targeting CAR-T cells against HSCs and AML tumour cell lines. 5T4 expression was seen in about 50% of AML cases, specifically AML with mutated NPM1, AML-MR and NOS. 5T4 CAR-T cells efficiently and specifically killed AML tumour cell lines, including the Leukaemic Stem Cells. Co-culture of 5T4 CAR-T cells with HSCs from healthy donors showed no impact on subsequent colony formation, thus confirming the safety profile of 5T4. A murine model for AML demonstrated that CAR-T cells recognise and kill in vivo 5T4-expressing tumour cells. These results highlight 5T4 as a promising target for immune intervention in AML and that CAR-T cells can be considered a powerful personalised therapeutic approach to treat AML.

Biosynthesis of metal/metal oxide nanoparticles via Deverra tortuosa: characterization, GC/MS profiles, and biological potential

Since the beginning of humanity, people have used wild medicinal plants for the treatment of various diseases. Nowadays, researchers and scientists pay attention to exploring new tools to maximize the efficacy of natural products from natural resources, and among these tools formulation of nanoparticles is very promising. The green synthesis of metal/metal oxide nano-solutions using the Deverra tortuosa extract has still not been explored well. This study aims to prepare many metal/metal oxide nanoparticle solutions such as ZnO-NPs, SeO2-MNPs, and Ag-NPs via the methanol extract of D. tortuosa as safe, easy, green, and economic approach as well as characterize the chemical components of D. tortuosa plant by GC-MS spectroscopy analysis. The synthesized M-NPs solutions were characterized by UV–visible (UV–Vis) spectroscopy, Transmission Electron Microscope (TEM), zeta potential, Fourier Transform Infrared (FT-IR) spectroscopy, and phytochemical analyses. The potential antioxidant capacity was estimated for the methanol extract of this plant along with the metal/metal oxide nanoparticles solutions by DPPH assay. In addition, the cytotoxic activity was in vitro assessed for the inspected samples against various tumor and normal cell lines applying MTT assay. The application of the D. tortuosa methanolic extract resulted in NPs with a range of 11.79–85.9 nm which was characterized by UV-Vis spectroscopy, TEM, zeta potential, and FT-IR spectroscopy that revealed various functional groups of the tested samples. The GC-MS analysis of the D. tortuosa methanolic extract showed the presence of 31 chemical compounds with 2-methyl-3-oxocyclopent-1-ene-1-carboxylic acid, methyl oleate, and 6-allyl-4,5-dimethoxybenzo[d][1,3]-dioxole as major constituents. The extract showed considerable antioxidant activity as well as antimicrobial activity that was assessed also against varied bacterial and fungal species. Remarkable potencies for the investigated metal/metal oxide nanoparticle solutions hinder the growth of the tumor cell lines, in addition to the growth of the microbial species. Based on the determined biological activities of the produced NPs, future study is recommended to characterize the pure authentic compounds that are identified within the D. tortuosa as major compounds as well as evaluate their modes of action.

EIF4A3-mediated oncogenic circRNA hsa_circ_0001165 advances esophageal squamous cell carcinoma progression through the miR-381-3p/TNS3 pathway

Esophageal squamous cell carcinoma (ESCC) remains a major clinical challenge due to its poor prognosis and the scarcity effective therapeutic targets. Circular RNAs (circRNAs) are crucial in cancer progression. In this study, high-throughput sequencing was employed to profile ESCC tissues, revealing that hsa_circ_0001165 is notably elevated in both ESCC tumor samples and cell lines, with its expression is positively associated with patients' TNM staging. Knockdown of hsa_circ_0001165 resulted in reduced malignant biological behavior of ESCC cells in vitro and also inhibited tumor growth in vivo. Mechanism experimental analysis found that hsa_circ_0001165 expression is positively enhanced by eukaryotic translation initiation factor 4A3 (EIF4A3). Hsa_circ_0001165 acts as a miRNA sponge for miR-381-3p, increasing the expression of tensin-3 (TNS3) through a series of related mechanism assays include dual-luciferase reporter gene, RNA Immunoprecipitation and RNA-pulldown. The downregulation in miR-381-3p expression was observed in ESCC tissues, and the cell proliferation, invasion, and migration of ESCC were suppressed. The upregulated expression of hsa_circ_0001165 modulates the miR-381-3p/TNS3 axis and promotes aggressive phenotypes of ESCC. Hsa_circ_0001165 is regarded as a encouraging biomarker and potential therapeutic target for ESCC, presenting innovative options for both diagnostic and treatment approaches.

Synthesis, pharmacological evaluation, and modeling of novel quaternary ammonium salts derived from β-carboline containing an imidazole moiety as angiogenesis inhibitors

In this study, a series of novel β-carboline condensed imidazolium derivatives (7a-7y) were designed and synthesized by incorporating imidazolium salt structures into β-carboline. The cytotoxicity of compounds 7a-7y was evaluated in various cancer cell lines, including lung cancer (A549), gastric cancer (BGC-823), mouse colon cancer (CT-26), liver cancer (Bel-7402), and breast cancer (MCF-7), using the MTT assay. Most compounds exhibited significant activity against one or more of the cancer cell lines. Notably, compounds 7 g, 7o, 7r, 7 s, 7u, 7v, 7x, and 7w showed the highest cytotoxic activity (IC50 < 2 μM) in the tested tumor cell lines. Compound 7x demonstrated cytotoxic activities of 1.3 ± 0.3 μM (for BGC-823), 2.4 ± 0.4 μM (against A549), 7.8 ± 0.9 μM (for Bel-7402), and 9.8 ± 1.4 μM (against CT-26). The chick chorioallantoic membrane assay revealed significant anti-angiogenic potential of compound 7x. Molecular imprinting studies suggested the anti-angiogenic effect of compound 7x might be attributed to inhibition of VEGFR2 kinase. Molecular docking and molecular dynamics further indicate that its activity may be primarily associated with the potential inhibition of VEGFR2. Our research outcomes have provided valuable lead compounds for the development of novel antitumor drugs and have offered beneficial insights for subsequent drug design and optimization.

ESR Essentials: staging and restaging with FDG-PET/CT in oncology-practice recommendations by the European Society for Hybrid, Molecular and Translational Imaging.

Positron emission tomography (PET) stands as the paramount clinical molecular imaging modality, especially in oncology. Unlike conventional anatomical-morphological imaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI), PET provides detailed visualizations of internal activity at the molecular and cellular levels. 18-fluorine-fluorodeoxyglucose ([18F]FDG)-PET combined with contrast-enhanced CT (ceCT) significantly improves the detection of various cancers. Appropriate patient selection is crucial, and physicians should carefully assess the appropriateness of [18F]FDG-PET/CT based on specific clinical criteria and evidence. Due to its high diagnostic accuracy, [18F]FDG-PET/CT is indispensable for evaluating the extent of disease, staging, and restaging known malignancies, and assessing the response to therapy. PET/CT imaging offers significant advantages in patient management, particularly by identifying occult metastases that might otherwise go undetected. This can help prevent unnecessary surgeries, allowing many patients to be redirected to systemic chemotherapy instead. However, it is important to note that the gold standard for surgical planning remains CT and/or MRI, depending on the body region. These imaging modalities, with or without associated angiography, provide superior contrast and spatial resolution, essential for detailed surgical preparation and planning. [18F]FDG-PET/CT has a central role in the precise and early diagnosis of cancer, contributing significantly to personalized treatment plans. However, it has limitations, including non-tumor-specific uptake and the potential to inaccurately capture the metabolic activity of certain tumor types due to low uptake in some well-differentiated tumor cell lines. Therefore, it should be utilized in clinical scenarios where it offers crucial diagnostic insights not readily available with other imaging modalities. KEY POINTS: Use [18F]FDG-PET/CT selectively based on clinical appropriateness criteria and existing evidence to optimize resource utilization and minimize patient exposure. Employ [18F]FDG-PET/CT in treatment planning and monitoring, particularly for assessing chemotherapy or radiotherapy response in FDG-avid lymphoma and solid tumors. When available, [18F]FDG-PET/CT can be integrated with other diagnostic tools, such as MRI, to enhance overall diagnostic accuracy.