Search Results (1,179)

The secondary metabolites of the fungus Penicillium thymicola, fumiquinazolines F and G, have antibacterial and antifungal characteristics; however, their potential anti-tumor action against human cancer cells remains unknown. The goal of our study was to determine the biological efficacy of fumiquinazolines F and G on breast and prostate cancer cells. Cancer cell proliferation and migration were monitored in real time using xCELLigence technology and flow cytometry. Alterations in mRNA and protein expression were assessed by RT-qPCR, ELISA, and Western blotting. Our data indicate that fumiquinazolines F and G are more effective in inhibiting breast cancer cell proliferation than prostate cancer cells. Fumiquinazoline F is active against both hormone-dependent epithelial MCF-7 (IC₅₀ 48 μM) and hormone-resistant triple-negative mesenchymal MDA-MB-231 breast cancer cells (IC₅₀ 54.1 μM). The metabolite has low cytotoxicity but slows cell cycle progression. In fumiquinazoline F-treated MDA-MB-231 cells, the levels of proteins implicated in epithelial–mesenchymal transition (EMT) (such as E-cadherin, vimentin, and CD44) fluctuate, resulting in a decrease in cell migratory rate and adhesion to a hyaluronic acid-coated substrate. Thus, fumiquinazolines F and G exhibit anticancer activity by inhibiting EMT, cell proliferation, and migration, hence reverting malignant cells to a less pathogenic phenotype. The compound’s multi-target anticancer profile underscores its potential for further exploration of novel EMT-regulating pathways. Full article

Prostate cancer is among the most prevalent malignancies in men worldwide, underscoring the need for early and accurate diagnostic tools. This study presents a proof-of-concept and pilot clinical validation of a novel bioelectric impedance-based biosensor for the detection of prostate-specific antigen (PSA) in human serum. The system integrates Molecular Identification through Membrane Engineering (MIME) with the xCELLigence real-time cell analysis platform, employing Vero cells electroinserted with anti-PSA antibodies. Optimization experiments identified 15,000 cells/well as the optimal configuration for impedance response. The biosensor exhibited specific, concentration-dependent changes in impedance upon exposure to PSA standard solutions and demonstrated significant differentiation between PSA-positive and PSA-negative human serum samples relative to the clinical threshold of 4 ng/mL. The biosensor offered rapid results within one minute, unlike standard immunoradiometric assay (IRMA), while showing strong diagnostic agreement. The system’s specificity, sensitivity, and reproducibility support its potential for integration into point-of-care screening workflows. This bioelectric assay represents one of the fastest PSA detection approaches reported to date and offers a promising solution for reducing overdiagnosis while improving clinical decision-making and patient outcomes. Full article

The human interpretation of medical images, especially for the detection of cancer in the prostate, has traditionally been a time-consuming and challenging process. Manual examination for the detection of prostate cancer is not only time-consuming but also prone to errors, carrying the risk of an excess biopsy due to the inherent limitations of human visual interpretation. With the technical advancements and rapid growth of computer resources, machine learning (ML) and deep learning (DL) models have been experimentally used for medical image analysis, particularly in lesion detection. However, several state-of-the-art models have shown promising results. There are still challenges when analysing prostate lesion images due to the distinctive and complex nature of medical images. This study offers an elaborate review of the techniques that are used to diagnose prostate cancer using medical images. The goal is to provide a comprehensive and valuable resource that helps researchers develop accurate and autonomous models for effectively detecting prostate cancer. This paper is structured as follows: First, we outline the issues with prostate lesion detection. We then review the methods for analysing prostate lesion images and classification approaches. We then examine convolutional neural network (CNN) architectures and explore their applications in deep learning (DL) for image-based prostate cancer diagnosis. Finally, we provide an overview of prostate cancer datasets and evaluation metrics in deep learning. In conclusion, this review analyses key findings, highlights the challenges in prostate lesion detection, and evaluates the effectiveness and limitations of current deep learning techniques. Full article

Background: Lysosomal-associated membrane protein 1 (LAMP1), typically localized to the lysosomal membrane, is increasingly implicated as a marker of cancer aggressiveness and metastasis when expressed on the cell surface. This study aimed to develop a LAMP1-targeted antibody-based PET tracer and assess its efficacy in mouse models of human breast and colon adenocarcinoma. Methods: To determine the source of LAMP1 expression, we utilized human single-cell RNA sequencing and spatial transcriptomics, complemented by in-house flow cytometry on xenografted mouse models. Tissue microarrays of multiple epithelial cancers and normal tissue were stained for LAMP-1, and staining was quantified. An anti-LAMP1 monoclonal antibody was conjugated with desferrioxamine (DFO) and labeled with zirconium-89 (⁸⁹Zr). Human triple-negative breast cancer (MDA-MB-231) and colon cancer (Caco-2) cell lines were implanted in nude mice. PET/CT imaging was conducted at 24, 72, and 168 h post-intravenous injection of ⁸⁹Zr-DFO-anti-LAMP1 and ⁸⁹Zr-DFO-IgG (negative control), followed by organ-specific biodistribution analyses at the final imaging time point. Results: Integrated single-cell and spatial RNA sequencing demonstrated that LAMP1 expression was localized to myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs) in addition to the cancer cells. Tissue microarray showed significantly higher staining for LAMP-1 in tumor tissue compared to normal tissue (3986 ± 2635 vs. 1299 ± 1291, p < 0.001). Additionally, xenograft models showed a significantly higher contribution of cancer cells than the immune cells to cell surface LAMP1 expression. In vivo, PET imaging with ⁸⁹Zr-DFO-anti-LAMP1 PET/CT revealed detectable tumor uptake as early as 24 h post-injection. The ⁸⁹Zr-DFO-anti-LAMP1 tracer demonstrated significantly higher uptake than the control ⁸⁹Zr-DFO-IgG in both models across all time points (MDA-MB-231 SUV_max at 168 h: 12.9 ± 5.7 vs. 4.4 ± 2.4, p = 0.003; Caco-2 SUV_max at 168 h: 8.53 ± 3.03 vs. 3.38 ± 1.25, p < 0.01). Conclusions: Imaging of cell surface LAMP-1 in breast and colon adenocarcinoma is feasible by immuno-PET. LAMP-1 imaging can be expanded to adenocarcinomas of other origins, such as prostate and pancreas. Full article

Two triterpene saponins, hederagenin glucosides, including a novel monodesmoside: 3-O-β-D-glucopyranosyl(1→3)-β-D-glucopyranosyl] hederagenin (compound 1), were isolated from the fruits of Oxybasis rubra (L.) S.Fuentes, Uotila & Borsh (Amaranthaceae). These compounds, together with hederagenin itself (compound 4) and a commercially available 28-O-β-D-glucopyranosyl hederagenin ester (compound 3), were evaluated for cytotoxicity and selectivity across a wide panel of human cancer cell lines (skin, prostate, gastrointestinal, thyroid, and lung). All four compounds exhibited dose- and time-dependent effects, with varying potency depending on the specific cancer type. The isolated bidesmosidic saponin (3-O-β-D-glucopyranosyl(1→3)-β-D-glucopyranosyl] hederagenin 28-O-β-D-glucopyranosyl ester—compound 2) showed the strongest activity and selectivity, with an IC₅₀ = 6.52 μg/mL after 48 h incubation against WM793 melanoma, and almost no effect on normal HaCaT skin cells (IC₅₀ = 39.94 μg/mL). Multivariate analysis of the obtained data using principal component analysis (PCA) and hierarchical cluster analysis (HCA) supported the assumption that cytotoxicity is influenced by the type of compound, its concentration, and the intrinsic sensitivity of the cell line. Structure-activity observations between closely related hederagenin derivatives are also briefly presented. Full article

Background/Objectives: Radiotherapy (RT) is a mainstay of clinical cancer therapy that causes broad immune responses. The complement system is a pivotal effector mechanism in the innate immune response, but the impact of RT is less well understood. This study investigates the interaction between RT and the complement system as a possible approach to improve immune responses in cancer treatment. Methods: Human solid cancer (lung, prostate, liver, breast cancer), lymphoma, and leukemia cells were irradiated using X-rays and treated with polyclonal antibodies or anti-CD20 monoclonal antibodies, respectively. Chromium release assay was applied to measure cell lysis after radiation with or without complement-activating antibody treatment. The expression of membrane-bound complement regulatory proteins (mCRPs; CD46, CD55, CD59), which confer resistance against complement activation, CD20 expression, apoptosis, and radiation-induced DNA double-strand breaks (γH2AX), was measured by flow cytometry. The radiosensitivity of tumor cells was assessed by colony-forming assay. Results: We demonstrate that RT profoundly impacts complement function by upregulating the expression of membrane-bound complement regulatory proteins (mCRPs) on tumor cells in a dose- and time-dependent manner. Impaired complement-mediated tumor cell lysis could thus potentially contribute to radiotherapeutic resistance. We also observed RT-induced upregulation of CD20 expression on lymphoma and leukemic cells. Notably, complement activation prior to RT proved more effective in inducing RT-dependent early apoptosis compared to post-irradiation treatment. While complement modulation does not significantly alter RT-induced DNA-damage repair mechanisms or intrinsic radiosensitivity in cancer cells, our results suggest that combining RT with complement-based anti-cancer therapy may enhance complement-dependent cytotoxicity (CDC) and apoptosis in tumor cells. Conclusions: This study sheds light on the complex interplay between RT and the complement system, offering insights into potential novel combinatorial therapeutic strategies and a potential sequential structure for certain tumor types. Full article

Positron emission tomography (PET) and liquid biopsy have independently transformed prostate cancer management. This review explores the complementary roles of PET imaging and liquid biopsy in prostate cancer, focusing on their combined diagnostic, monitoring, and prognostic potential. A systematic search of PubMed, Scopus, and Cochrane Library databases was conducted to identify human studies published in English up to January 2025. Seventeen studies met the inclusion criteria and were analyzed according to PRISMA guidelines. Across the included studies, PET-derived imaging metrics, such as metabolic activity and radiotracer uptake, correlated consistently with liquid biopsy biomarkers, including circulating tumor cells and cell-free DNA. Their joint application demonstrated added value in early detection, treatment monitoring, and outcome prediction, particularly in castration-resistant prostate cancer. Independent and synergistic prognostic value was noted for both modalities, including survival outcomes such as overall survival and progression-free survival. Combining PET imaging and liquid biopsy emerges as a promising, non-invasive strategy for improving prostate cancer diagnosis, monitoring, and therapeutic stratification. While preliminary findings are encouraging, large-scale prospective studies are essential to validate their integrated clinical utility. Full article

Background/Objectives: Prostate cancer is the second most common type of cancer diagnosed in men. Various treatments for this cancer, such as radiation therapy, surgery, and systemic therapy, can cause side effects in patients; therefore, there is a need to develop new treatment alternatives. One promising approach is virotherapy, which involves using oncolytic viruses (OVs), such as the recombinant Newcastle disease virus (rNDV). Methods: We used the lentogenic rNDV rLS1 strain (the control virus) as our backbone to develop two highly fusogenic rNDVs: rFLCF5nt (the parental virus) and rFLCF5nt-IFN-γ (rFLCF5nt expressing human interferon-gamma (IFN-γ)). We evaluated their oncolytic properties in a prostate cancer cell line (DU145). Results: The results showed the expression and stability of the IFN-γ protein, as confirmed using Western blotting after ten passages in specific pathogen-free chicken embryo eggs using the IFN-γ-expressing virus. Additionally, we detected a significantly high oncolytic activity in DU145 cells infected with the parental virus or the IFN-γ-expressing virus using MTS (a cell viability assay) and Annexin V-PE assays compared with the control virus (p < 0.0001 for both). Conclusions: In conclusion, our data show that IFN-γ-expressing virus can decrease cell viability and induce apoptosis in human prostate cancer in vitro. Full article

Jumping translocations (JTs) are rare chromosomal abnormalities that play a crucial role in the pathogenesis of various cancer types. These rearrangements, especially those involving chromosome 1q, are frequently associated with tumor progression, therapeutic resistance, and poor prognosis. One gene of particular interest, human Jumping Translocation Breakpoint (JTB), has been identified at the site of translocation breakpoints and exhibits complex, context-dependent roles in cancer biology. JTB protein functions as a pivotal regulator in mitosis, chromosomal segregation, apoptosis, and cellular metabolism. It is functionally linked with the chromosomal passenger complex (CPC) and is implicated in processes such as epithelial–mesenchymal transition (EMT), immune evasion, and therapy resistance, especially in breast and prostate cancers. Advances in genomic, transcriptomic, and proteomic research have highlighted the significant potential of JTB as a diagnostic biomarker and a target for therapeutic interventions. This review underscores the dual role of JTB as both a tumor suppressor and oncogene, depending on the cellular context, and advocates for its continued investigation at the genomic, transcriptomic, and proteomic levels. Understanding JTB’s multifaceted contributions to tumor biology may pave the way for novel biomarkers and targeted treatments in cancer management. Full article

A series of novel derivatives of 3-amino-4-hydroxybenzenesulfonamide was synthesized. As the analyzed compounds possess a sulfonamide group, the affinity of these compounds for human carbonic anhydrases (CAs) was measured by fluorescent thermal shift assay, and compound selectivity for different isoenzymes was identified. The crystal structures of the complexes of compound 25 with CAI and CAII were determined. Additionally, the activity of compounds on the viability of three cancer cell lines—human glioblastoma U-87, triple-negative breast cancer MDA-MB-231, and prostate adenocarcinoma PPC-1—was established using the MTT assay and compared to CAIX-selective and non-selective comparative compounds U-104 and acetazolamide. The half-maximal concentration (EC₅₀) was determined for the identified most active compounds, and their selectivity over fibroblasts was established. Compound 9 (inhibitor of multi-CAs) and compound 21 (not binding to CAs), considered the most promising candidates, were tested in cancer cell 3D cultures (cancer spheroids) by assessing their effect on spheroid growth and viability. Both compounds reduced the viability of spheroids from all cancer cell lines. U-87 and PPC-1 spheroids became looser in the presence of compound 9, while the growth of MDA-MB-231 spheroids was slower compared to the control. Compound 21 reduced the growth of U-87 and MDA-MB-231 3D cultures, with no significant effect on PPC-1 spheroids. Full article

Background/Objectives: Radiolabeled biomolecules specifically targeting overexpressed structures on tumor cells hold great potential for prostate cancer (PCa) imaging and therapy. Due to heterogeneous target expression, single radiopharmaceuticals may not detect or treat all lesions, while simultaneously applying two or more radiotracers potentially improves staging, stratification, and therapy of cancer patients. This study explores a dual-tracer SPECT approach using [¹¹¹In]In-RM2 (targeting the gastrin-releasing peptide receptor, GRPR) and [^99mTc]Tc-PSMA-I&S (targeting the prostate-specific membrane antigen, PSMA) as a proof of concept. To mimic heterogeneous tumor lesions in the same individual, we aimed to establish a dual xenograft mouse model for preclinical evaluation. Methods: CHO-K1 cells underwent lentiviral transduction for human GRPR or human PSMA overexpression. Six-to-eight-week-old female immunodeficient mice (NOD SCID) were subsequently inoculated with transduced CHO-K1 cells in both flanks, enabling a dual xenograft with similar target density and growth of both xenografts. Respective dual-isotope imaging and γ-counting protocols were established. Target expression was analyzed ex vivo by Western blotting. Results: In vitro studies showed similar target-specific binding and internalization of [¹¹¹In]In-RM2 and [^99mTc]Tc-PSMA-I&S in transduced CHO-K1 cells compared to reference lines PC-3 and LNCaP. However, in vivo imaging showed negligible tumor uptake in xenografts of the transduced cell lines. Ex vivo analysis indicated a loss of the respective biomarkers in the xenografts. Conclusions: Although the technical feasibility of a dual-tracer SPECT imaging approach using ¹¹¹In and ^99mTc has been demonstrated, the potential of [^99mTc]Tc-PSMA-I&S and [¹¹¹In]In-RM2 in a dual-tracer cocktail to improve PCa diagnosis could not be verified. The animal model, and in particular the transduced cell lines developed exclusively for this project, proved to be unsuitable for this purpose. The in/ex vivo experiments indicated that results from an in vitro model may not necessarily be successfully transferred to an in vivo setting. To assess the potential of this dual-tracer concept to improve PCa diagnosis, optimized in vivo models are needed. Nevertheless, our strategies address key challenges in dual-tracer applications, aiming to optimize future SPECT imaging approaches. Full article

Natural compounds remain a valuable source of anticancer agents due to their structural diversity and multi-targeted mechanisms of action. Roburic acid (RA), a tetracyclic triterpenoid, has been identified as a substance capable of inhibiting key NF-κB and MAPK signaling pathways through direct interaction with TNF-α, as well as preventing the production of inflammatory mediators and cancer progression. In this study, we evaluated the biological activity of RA against a panel of human cancer cell lines—DLD-1, HT-29, and HCT-116 (colorectal), PC-3 (prostate), and BxPC-3 (pancreatic)—as well as two non-malignant lines: WI-38 (fibroblasts) and CCD-841 CoN (colon epithelium). RA exhibited a concentration-dependent inhibitory effect on cancer cell metabolic activity, with colorectal cancer cells showing relatively higher sensitivity, particularly at shorter incubation times. To distinguish between cytotoxic and cytostatic effects, we performed trypan blue exclusion combined with a cell density assessment, clonogenic assay, and BrdU incorporation assay. The results from these complementary assays confirmed that RA acts primarily through an antiproliferative mechanism rather than by inducing cytotoxicity. In addition, NF-κB reporter assays demonstrated that RA attenuates TNF-α-induced transcriptional activation at higher concentrations, supporting its proposed anti-inflammatory properties and potential to modulate pro-tumorigenic signaling. Finally, our in silico studies predicted that RA may interact with proteins such as CAII, CES1, EGFR, and PLA2G2A, implicating it in the modulation of pathways related to proliferation and cell survival. Collectively, these findings suggest that RA may serve as a promising scaffold for the development of future anticancer agents, particularly in the context of colorectal cancer. Full article

Background/Objectives: There is a growing need for efficient prostate MRI protocols due to their increasing use in managing prostate cancer (PCa) and potential inclusion in screening. Deep learning reconstruction (DLR) may enhance MR acquisitions and improve image quality compared to conventional acceleration techniques. This systematic review examines DLR approaches to prostate MRI. Methods: A search of PubMed, Web of Science, and Google Scholar identified eligible studies comparing DLR to conventional reconstruction for prostate imaging. A narrative synthesis was performed to summarize the impact of DLR on acquisition time, image quality, and diagnostic performance. Results: Thirty-three studies showed that DLR can reduce acquisition times for T₂w and DWI imaging while maintaining or improving image quality. It did not significantly affect clinical tasks, such as biopsy decisions, and performed comparably to human readers in PI-RADS scoring and the detection of extraprostatic extension. However, AI models trained on conventional data might be less accurate with DLR images. The heterogeneity in image quality metrics among the studies prevented quantitative synthesis. Discussion: DLR has the potential to achieve substantial time savings in prostate MRI while maintaining image quality, which is especially relevant because of increased MRI demands. Future research should address the effect of DLR on clinically relevant downstream tasks, including AI algorithms’ performances and biopsy decisions, and explore task-specific accelerated protocols for screening, image-guided biopsy, and treatment. Full article

Background/Objectives: The 3-dimensional (3D) architecture of the genome in the nucleus of a living cell plays an unexpected yet fundamental regulatory role in cell biology. As an imprint of the cellular genetic, epigenetic and metabolic status, it discriminates pathological conditions through conditional changes to long-range 3D interactions (up to 300 kb) and thus could act as a powerful molecular biomarker linked closely to clinical outcomes. Methods: Here an assessment is made of the latest paradigm shift in molecular biology from a supply chain where information flows from DNA to RNA to protein, to the concept of heritable 3D folding of the genome reflecting the epigenetic and metabolic state of the cell, and which serves as a molecular biomarker for complex clinical outcome. Results: While biomarkers based on individual components of the supply chain fail to accurately reflect clinical outcomes, 3D genomics offers highly informative insights, exemplified for immuno-oncology and prostate cancer diagnosis by clinical tests of superior performance, already in practice in the US and UK. Conclusions: A more complete understanding of human biology will require models that account for the flow of information to and from the 3D genomic architecture in living cells, together with its regulation and logic. Integrating these principles into biomarker discovery and therapeutic design, along with other frontline approaches in precision medicine, including multi-omics and other system-level tools, will be essential for advancing precision medicine beyond its current limitations. Full article

Species belonging to the genus Cnidoscolus have been widely recognized for their diverse applications, including forage, oil production, latex, ornamental purposes, medicinal uses, and as nutritional sources. This study aimed to compile up-to-date information on the chemical, nutritional, and ethnopharmacological aspects, as well as the biological activities, of Cnidoscolus species, offering a critical overview of the current advancements in research on these plants. The reviewed literature indicates that Cnidoscolus species hold significant traditional use value, particularly in the treatment of conditions such as cancer, diabetes, and disorders affecting the uterus, prostate, ovaries, and kidneys, in addition to menstrual disturbances, inflammation, and general pain. Scientifically, their efficacy has been demonstrated in several contexts, including antinociceptive, antibacterial, anti-inflammatory, cytotoxic, antiproliferative, hypoglycemic, and antioxidant activities, among others. Additionally, certain species like C. aconitifolius have shown potential for human consumption, with leaves being eaten raw or cooked, while C. quercifolius demonstrates nutritional value in its seeds, which can be utilized in the development of functional foods. However, further studies are needed to focus on the isolation and characterization of bioactive compounds found in these species, as well as deeper investigations into the molecular and cellular mechanisms underlying their biological activities and assessments of the safety of long-term consumption in both humans and animals. Moreover, more extensive clinical and preclinical studies are essential to validate the proposed therapeutic effects and to support the safe and effective inclusion of these species in conventional treatment regimens. Full article