Search Results (6,453)

Prostate cancer (PCa) is a heterogeneous disease that exhibits androgen sensitivity and responsiveness to androgen deprivation therapy (ADT). However, ADT induces only temporary remission, and the majority of PCa cases eventually progress to castration-resistant PCa (CRPC). During the development and progression of CRPC, androgen sensitivity and androgen receptor (AR) dependency in PCa cells are often deceased or lost due to ADT or spontaneously arising AR variants even before starting ADT. To prevent CRPC, a clinical PCa model derived from an AR-positive cancer cell line with weak or no androgen sensitivity is required. The human prostate LNCaP cell line is a good model for PCa because of its androgen sensitivity and AR dependency in terms of cell growth and gene expression. Notably, LNCaP cells are heterogeneous cells comprising different clones with natural variations in androgen sensitivity and AR dependency resulting from spontaneously occurring changes. In our group, to obtain androgen-insensitive or weakly sensitive clones spontaneously derived from parental LNCaP cells, we performed a limiting dilution of parental LNCaP cells and obtained several sublines with varying levels of androgen sensitivity and AR dependency. In addition, we established an androgen-insensitive subline from parental LNCaP cells by continuous passage under hormone-depleted conditions. This article provides a unique perspective on our original PCa progression model interacting with fibroblasts and its application in preclinical research. Full article

Over the past decade, prostate-specific membrane antigen positron emission tomography (PSMA-PET) has revolutionized prostate cancer (PCa) imaging, offering greater sensitivity and specificity compared to conventional imaging modalities such as CT, MRI, and bone scintigraphy. PSMA-PET is particularly valuable in staging newly diagnosed patients with intermediate- and high-risk disease, detecting biochemical recurrence, and evaluating metastatic cases. By utilizing radiotracers that accumulate specifically in PSMA-expressing cells, even small metastases can be detected, offering a detailed assessment of cancer extent and enabling more targeted diagnostic evaluations. Among the most utilized radiotracers, [⁶⁸Ga]- and [¹⁸F]-labeled PSMA tracers enable precise imaging even with low disease burden. This diagnostic precision also supports advanced therapeutic approaches, including metastasis-directed therapy for oligometastatic cases and systemic treatment options, such as radioligand therapy, which presents new treatment perspectives for metastatic, castration-resistant PCa. This review examines the evolution of PSMA-PET in the diagnostics and therapy of PCa while comparing the current recommendations from leading clinical guidelines. The integration of PSMA-PET into clinical practice has redefined the management of PCa, improving diagnostic accuracy and enabling personalized treatment strategies, while lacking prospective long-term outcome data. As PSMA-PET continues to expand in clinical application, this review highlights its significant advancements while critically addressing limitations to ensure balanced and evidence-based implementation in prostate cancer care. Full article

Building on a previously developed partially synthetic data generation algorithm utilizing data visualization techniques, this study extends the novel algorithm to generate fully synthetic tabular healthcare data. In this enhanced form, the algorithm serves as an alternative to conventional methods based on Generative Adversarial Networks (GANs) or Variational Autoencoders (VAEs). By iteratively applying the original methodology, the adapted algorithm employs UMAP (Uniform Manifold Approximation and Projection), a dimensionality reduction technique, to validate generated samples through low-dimensional clustering. This approach has been successfully applied to three healthcare domains: prostate cancer, breast cancer, and cardiovascular disease. The generated synthetic data have been rigorously evaluated for fidelity and utility. Results show that the UMAP-based algorithm outperforms GAN- and VAE-based generation methods across different scenarios. In fidelity assessments, it achieved smaller maximum distances between the cumulative distribution functions of real and synthetic data for different attributes. In utility evaluations, the UMAP-based synthetic datasets enhanced machine learning model performance, particularly in classification tasks. In conclusion, this method represents a robust solution for generating secure, high-quality synthetic healthcare data, effectively addressing data scarcity challenges. Full article

Abstract: Introduction: Prostate cancer treatment has been revolutionized by targeted therapies, including PARP inhibitors, checkpoint immunotherapies, and PSMA-targeted radiotherapies. Despite such advancements, accurate patient stratification remains a challenge, with current methods relying on genomic markers, tissue staining, and imaging. Extracellular vesicle (EV)-derived proteins offer a novel non-invasive alternative for biomarker discovery, holding promise for improving treatment precision. However, the characterization of plasma-derived EVs in prostate cancer patients remains largely unexplored. Methods: We conducted proteomic analyses on EVs isolated from plasma in 27 metastatic castration-resistant prostate cancer (mCRPC) patients. EVs were purified using ultracentrifugation and analyzed via mass spectrometry. Proteomic data were correlated with clinical markers such as serum prostate-specific antigen (PSA) and bone lesion counts. Statistical significance was assessed using Mann–Whitney t-tests and Spearman correlation. Results: The median age of patients was 74 (range: 44–94) years. At the time of blood collection, the median PSA level was 70 (range: 0.5–1000) ng/mL. All patients had bone metastasis. A total of 5213 proteins were detected, including EV-related proteins (CD9, CD81, CD63, FLOT1, TSG101) and cancer-related proteins (PSMA, B7-H3, PD-L1). Proteomic profiling of plasma EVs revealed a significant correlation between specific EV-derived proteins and clinical prognostic markers. B7-H3, LAT1, and SLC29A1 showed a strong association with serum PSA levels and number of bone lesions, indicating potential for these proteins to serve as biomarkers of disease burden and therapy response. Conclusions: Our findings demonstrate the potential of EV-based proteomics for identifying biomarkers in mCRPC patients. Proteins such as B7-H3 and LAT1 could guide precision oncology approaches, improving patient stratification. Future research incorporating outcomes data and EV subpopulation analysis is needed to establish clinical relevance. Full article

Breast cancer is a significant cause of death from cancer in women globally, highlighting the need for improved diagnostic imaging to enhance patient outcomes. Accurate tumor identification is essential for diagnosis, treatment, and monitoring, emphasizing the importance of advanced imaging technologies that provide detailed views of tumor characteristics and disease. Recently, a new imaging modality named synthetic correlated diffusion imaging (CDI^s) has been showing promise for enhanced prostate cancer delineation when compared to existing MRI imaging modalities. In this study, we explore the efficacy of optimizing the correlated diffusion imaging (CDI) protocol to tailor it for breast cancer tumor delineation. More specifically, we optimize the coefficients of the calibrated signal mixing function in the CDI^s protocol that controls the contribution of different gradient pulse strengths and timings by maximizing the area under the receiver operating characteristic curve (AUC) across a breast cancer patient cohort. Experiments showed that the optimized CDI^s can noticeably increase the delineation of breast cancer tumors by over 0.03 compared to the unoptimized form, as well as providing the highest AUC when compared with gold-standard modalities. These experimental results demonstrate the importance of optimizing the CDI^s imaging protocol for specific cancer applications to yield the best diagnostic imaging performance. Full article

Despite treatment, prostate cancer commonly progresses into castration-resistant prostate cancer (CRPC), which remains largely incurable, requiring the development of new interventions. Darolutamide is an orally administered second-generation androgen receptor inhibitor indicated for patients with non-metastatic CRPC or metastatic hormone-sensitive prostate cancer. Here, we evaluated the effect of androgen receptor (AR) inhibition by darolutamide in combination with DNA double-strand-break-inducing targeted radium-223 alpha therapy in vitro and in an intratibial LNCaP xenograft model mimicking prostate cancer metastasized to bone. The results highlight the synergistic antitumor efficacy of darolutamide in combination with radium-223 both in vitro and in vivo. This effect was most likely driven by the downregulation of genes involved in DDR signaling, which was demonstrated in vitro by a gene set enrichment analysis. The combination treatment also reduced pathological tumor-induced effects in bone by decreasing the number of osteoblasts and osteoclasts and reducing abnormal bone formation in tumor-bearing bone. Additionally, it was shown that darolutamide does not affect the uptake of radium-223 into bone tissue. These results support the investigation of darolutamide in combination with radium-223 for the treatment of patients with CRPC metastasized to bone. Full article

Background/Objectives: Prostate cancer (PCa) outcomes vary significantly across risk groups. In early-stage localized PCa, the functional outcomes following radical prostatectomy (RP) can be severe, prompting increased interest in focal therapy, particularly High-Intensity Focused Ultrasound (HIFU). This study is to summarize the current clinical trials of HIFU on PCa. Methods: We reviewed clinical trials from major databases, including PubMed, MEDLINE, Scopus, and EMBASE, to summarize the current research on HIFU in PCa treatment. Results: The literature highlights that HIFU may offer superior functional outcomes, particularly in continence recovery, compared to RP and radiation therapy. However, the oncological efficacy of HIFU remains inadequately supported by high-quality studies. Focal and hemigland ablations carry a risk of residual significant cancer, necessitating comprehensive patient counseling before treatment. For post-HIFU monitoring, we recommend 3T magnetic resonance imaging (MRI) with biopsy at 6 to 12 months to reassess the cancer status. Biochemical recurrence should be defined using the Phoenix criteria, and PSMA PET/CT can be considered for identifying recurrence in biopsy-negative patients. Conclusions: Whole-gland ablation is recommended as the general approach, as it provides a lower PSA nadir and avoids the higher positive biopsy rates observed after focal and hemigland ablation in both treated and untreated lobes. Future study designs should address heterogeneity, including variations in recurrence definitions and surveillance strategies, to provide more robust evidence for HIFU’s oncological outcomes. Full article

In diagnostics, photons are used in basic methods such as computed tomography (CT) and positron emission tomography (PET), which are pivotal tools for high-resolution, non-invasive tumor detection, offering insights into tumor staging and progression. Mentioned techniques facilitate early diagnosis and the planning of therapeutic strategies. However, new methods are emerging, enhancing the precision and detail of diagnostics, such as ultra-weak photon emission (UPE) imagining, two-photon fluorescence imaging, photo acoustic imaging, and others. Therapeutically, external beam radiation therapy (EBRT) uses photons to target cancer cells while minimizing harm to healthy tissue. Photodynamic therapy (PDT), which uses light-sensitive compounds activated by specific wavelengths, represents a photon-based treatment applicable to certain malignancies. Other treatments include photo thermal therapy (PTT), radio dynamic therapy (RDT), intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and more. These constantly evolving photon-driven technologies can be used to treat a broad spectrum of cancers, such as pancreatic, prostate, breast, and skin cancers. This review article discusses the latest photon-based methods in oncology, focusing on new possibilities, solutions, perspectives, and the potential disadvantages of these approaches. Full article

Prostate cancer remains a significant global health concern, prompting ongoing exploration of novel therapeutic agents. Licochalcone A, a natural product in the chalcone family isolated from licorice root, is characterized by its enone structure and demonstrates antiproliferative activity in the micromolar range across various cell lines, including prostate cancer. Building on our prior success in enhancing curcumin’s antiproliferative potency by replacing the substituted phenol with a 1-alkyl-1H-imizadol-2-yl moiety, we applied a similar approach to design a new class of licochalcone A-inspired chalcones. The synthesis of these target chalcones involved key [3,3]-sigmatropic rearrangement of aryl prenyl ethers and Claisen–Schmidt condensations, yielding three derivative series. These compounds were evaluated for antiproliferative activity in both androgen receptor (AR)-positive and AR-null prostate cancer cell models using WST-1 cell proliferation assay. Systematic evaluation of licochalcone A across four prostate cancer cell lines indicated a modest advantage over enzalutamide, an FDA-approved AR antagonist, in suppressing 22Rv1 cell proliferation. Interestingly, three ester derivatives by replacing the phenol next to the carbonyl with an alkoxide demonstrated similar antiproliferative potency to licochalcone A in both AR-positive and AR-negative prostate cancer cell lines. This suggests that the phenol moiety on licochalcone A may be a promising site for chemical manipulations to enhance anti-prostate cancer activity. Among the synthesized chalcones, nine derivatives showed improved selectivity for AR-positive LNCaP and 22RV1 cells relative to AR-negative PC-3 and DU145 cells, surpassing licochalcone A in selectivity. Additionally, the antiproliferative potency was highly dependent on the R group attached to the imidazole. Most of the derivatives showed antiproliferative potency against androgen receptor-positive LNCaP and 22Rv1 cells, comparable to that of enzalutamide and licochalcone A. These findings suggest that optimization of licochalcone A-inspired chalcones as potential anti-prostate cancer agents warrants further investigation. Full article

The rising incidence of prostate cancer necessitates innovative treatment approaches, particularly as diseases such as the COVID-19 pandemic can disrupt traditional cancer care. This study aims to evaluate the impact of hypofractionated versus conventionally fractionated radiotherapy on prostate cancer cell lines in vitro. Prostate cancer cell lines (PC-3 and DU-145) were exposed to varying doses of radiation alongside non-cancerous BPH-1 cells. We assessed radiation effects on cell proliferation, viability, colony formation, DNA repair, migration, invasion, and cytotoxicity. The results demonstrated that the prostate cell lines exhibited varying responses, with hypofractionation favourably impacting aggressive PC-3 cells while preserving non-cancerous cells. In contrast, conventional fractionation led to increased invasion and cytotoxicity in both prostate cancerous cell lines. These findings advocate for personalised radiation therapy approaches that enhance treatment efficacy by considering the distinct behaviours of differing prostate cancer subtypes. Full article

Background: Epigenetic dysregulation is a common feature of cancer. Promoter demethylation of tumor-promoting genes and global DNA hypomethylation may trigger tumor progression. Epigenetic changes are unstable; thus, research has focused on detecting remedies that target epigenetic regulators. Previous studies have suggested that concordantly targeting hypomethylation and hypermethylation is beneficial for suppressing both the oncogenic and pro-metastatic functions of cancer cells. Therefore, we aimed to investigate the effect of a combination of S-adenosylmethionine (SAM) and the demethylating agent decitabine on prostate cancer cells. Materials and Methods: Prostate cancer cells (PC-3) were treated with SAM, decitabine, or a combination of both. Proliferation, migration, invasion, and methylation assays were also performed. A transcriptome study was conducted to detect different gene clusters between the treatment groups, followed by analyses using the Kyoto Encyclopedia of Genes and Genomes pathway and ingenuity pathway analysis. Finally, to gain information on differential gene expression, promoter methylation studies were performed. Results: Groups treated with decitabine, SAM, or their combination showed reduced proliferative capacity. The decitabine-treated group showed a marginal increase in cell migration and invasion, whereas the SAM-treated and combination treatment groups showed reduced invasion and migration potential. Methylation assays demonstrated the restoration of decitabine-induced demethylation in prostate cancer samples, whereas the transcriptome study revealed the upregulation of different gene clusters between the treatment groups. Methylation studies confirmed that SAM could restore the decitabine-induced demethylation of proto-oncogenes, but it did not induce the re-methylation of tumor-suppressor genes. Conclusions: Combination treatment with SAM and decitabine had an additive effect and did not nullify each other. Full article

Prostate cancer (PCa) is a common malignancy in men and is among the leading causes of cancer-related death worldwide. Genomic tests assess disease aggressiveness and guide treatment, particularly in low- and intermediate-risk PCa. We reviewed the literature on the use of four genomic tests (Prolaris^®, Promark^®, Oncotype DX^®, and Decipher^®) in assessing the prognosis of PCa and their use in treatment decision-making. Most of the studies showed that Prolaris^® has a strong correlation with biochemical recurrence, metastasis risk, PCa-specific mortality (PCSM), and pathological features. Similarly, three studies on Promark^® indicated a connection between results and pathological features in the subsequent prostatectomy, time to metastasis, and biochemical recurrence. Fourteen studies on Oncotype DX^® showed a clear correlation between high scores, death, and PCSM. One study found that routine biopsy pathology reports, combined with serum PSA levels, provide a risk assessment comparable to Oncotype DX^® testing. Results from 22 studies on Decipher^® were controversial. The test was associated with conservative management, suggesting that patients with a high GC score are more likely to need radiation after surgery. Comparative studies indicated that Oncotype DX^® is preferable for assessing PCSM, Decipher^® for predicting metastasis, and Prolaris^® for predicting recurrence. With the incidence rate of PCa dramatically increasing, genomic tests appear to be useful adjunctive precision medicine tools with significant potential in improving prognostic discrimination, facilitating better risk stratification, and guiding personalized treatment, especially in the intermediate-risk patient group. Large-scale, prospective, multi-sectional studies are required to validate the utility of these tests prior to their integration into clinical practice. Full article

Background: Renal cell carcinoma is one of the most aggressive urogenital malignancies, with an increasing number of cases worldwide. The majority of cases are diagnosed at an advanced stage, as this form of growth is typically silent. An accurate evaluation of the extent of the disease is crucial for selecting the most appropriate treatment approach. Nuclear medicine imaging is increasingly being applied in oncological diagnostics, prompting ongoing research into renal cell carcinoma markers that could serve as a foundation for theranostic approaches in this disease. Positron emission tomography/computed tomography imaging with prostate-specific membrane antigen (PSMA) ligands has already demonstrated successful utility in diagnosis of other cancers, including prostate cancer and gliomas. Emerging evidence of high sensitivity and specificity in detecting renal cell carcinoma lesions provides a suitable foundation for its application in both the diagnosis and subsequent management of this malignancy. Methods: This systematic review synthesizes the current scientific evidence on the molecular imaging of renal cell carcinoma using PSMA ligands, emphasizing the potential future applications of this imaging marker in theranostic approaches. Results and Conclusions: Based on a systematic review of the literature, it appears that PET/CT with PSMA ligands has the potential to surpass traditional imaging techniques in diagnostic accuracy while also providing valuable prognostic information. Full article

Xanthohumol (XN) is a phenolic compound found in the largest amount in the flowers of the hop plant, but also in the leaves and possibly in the stalks, which is successfully added to dietary supplements and cosmetics. XN is known as a potent antioxidant compound, which, according to current research, has the potential to prevent and inhibit the development of diseases, i.e., cancer and neurodegenerative diseases. The review aims to examine the antioxidant role of XN in disease prevention, with an emphasis on the benefits and risks associated with its supplementation. The regulation by XN of the Nrf2/NF-kB/mTOR/AKT (Nuclear factor erythroid 2-related factor 2/Nuclear factor kappa-light-chain-enhancer of activated B cells/Mammalian target of rapamycin/Protein Kinase B) pathways induce a strong antioxidant and anti-inflammatory effect, among others the acceleration of autophagy through increased synthesis of Bcl-2 (B-cell lymphoma 2) proteins, inhibition of the synthesis of VEGF (Vascular-endothelial growth factor) responsible for angiogenesis and phosphorylation of HKII (Hexokinase II). It is the key function of XN to ameliorate inflammation and to promote the healing process in organs. However, existing data also indicate that XN may have adverse effects in certain diseases, such as advanced prostate cancer, where it activates the AMPK (activated protein kinase) pathway responsible for restoring cellular energy balance. This potential risk may explain why XN has not been classified as a therapeutic drug so far and proves that further research is needed to determine the effectiveness of XN against selected disease entities at a given stage of the disease. Full article

Background: stereotactic ablative body radiotherapy (SABR) is a disruptive radiation therapy technique which is increasingly used for the treatment of urologic cancers. The aim of this narrative review is to provide an overview on the current landscape of SABR in urologic cancers and highlight advancements on the horizon. Methods: a narrative review of the contemporary role of SABR in urologic cancers is conducted. Results: in localised prostate cancer, SABR boasts excellent tumour control and biochemical control, with acceptable GU and GI toxicity. Its comparison to laparoscopic radical prostatectomy is currently ongoing. SABR appears to be practical for metastasis-directed therapy in metastatic prostate cancer, with good local control and a low toxicity profile, either alone or in combination with ADT. In localised RCC, SABR offers adequate local control with a modest impact on renal function in patients unfit for surgical management. Its role in metastatic RCC is much more established, where it has been shown to be superior to conventional radiotherapy. Emerging evidence suggests that SABR has a role in delaying systemic therapy whilst maintaining QOL and overall survival. Intriguingly, in metastatic prostate cancer and metastatic RCC, SABR results in a cytoreductive and immunomodulatory ‘abscopal effect’, a focus of current investigations. Conclusions: SABR has emerged as a safe, effective, and feasible treatment for urologic cancers. Urologists should be aware of its increasing use in localised prostate cancer and metastatic RCC, with good oncological outcomes combined with acceptable toxicity. In addition, SABR holds promise for both metastatic prostate cancer and localised RCC treatment in terms of toxicity and oncological outcomes. Full article