Search Results (4,067)

Background/Objectives: Prostate cancer (PCa) is characterised by its progression to a metastatic and castration-resistant phase. Prostate tumour cells release small extracellular vesicles or exosomes which are taken up by target cells and can potentially facilitate tumour growth and metastasis. The present work studies the effect of exosomes from cell lines that are representative of the different stages of the disease on the tumoral phenotype of PC3 cells. Methods: Exosomes were isolated by ultracentrifugation from human prostate epithelial cells (RWPE-1) and androgen-dependent PCa cells (LNCaP) and castration-resistant PCa cells (CRPC) with moderate (DU145) or high (PC3) metastatic capacity. The biophysical and biochemical properties of the exosomes were characterised as well as their effects on PC3 cell viability and migration. Results: The study of the exosomes of prostate cell lines shows heterogeneity in their size, presenting in some of them two types of populations; in both populations, a larger size in those derived from PC3 cells and a smaller size in those derived from non-tumourigenic prostate cells were detected. Differences were found in the physical properties of those derived from healthy and PCa cells, as well as between cells representative of the most aggressive stages of the disease. The highest gamma-glutamyl transferase (GGT) activity was observed in androgen-dependent cells and differences in the pro-metalloproteinases (MMP) activity were detected in healthy cells and in castration-resistant cells with moderate metastatic capacity with respect to PC3 cells. The treatment of PC3 cells with their own exosomes increased PC3 cell viability and migration. Conclusion: Exosomes represent a promising field of research in the diagnosis, prognosis, and treatment of prostate cancer. Full article

Due to their biocompatibility, nontoxicity, and surface conjugation properties, nanomaterials are effective nanocarriers capable of encapsulating chemotherapeutic drugs and facilitating targeted delivery across the blood–brain barrier (BBB). Although research on nanoparticles for brain cancer treatment is still in its early stages, these systems hold great potential to revolutionize drug delivery. Glioblastoma multiforme (GBM) is one of the most common and lethal brain tumors, and its heterogeneous and aggressive nature complicates current treatments, which primarily rely on surgery. One of the significant obstacles to effective treatment is the poor penetration of drugs across the BBB. Moreover, GBM is often referred to as a “cold” tumor, characterized by an immunosuppressive tumor microenvironment (TME) and minimal immune cell infiltration, which limits the effectiveness of immunotherapies. Therefore, developing novel, more effective treatments is critical to improving the survival rate of GBM patients. Current strategies for enhancing treatment outcomes focus on the controlled, targeted delivery of chemotherapeutic agents to GBM cells across the BBB using nanoparticles. These therapies must be designed to engage specialized transport systems, allowing for efficient BBB penetration, improved therapeutic efficacy, and reduced systemic toxicity and drug degradation. Lipid and inorganic nanoparticles can enhance brain delivery while minimizing side effects. These formulations may include epitopes—small antigen fragments that bind directly to free antibodies, B cell receptors, or T cell receptors—that interact with transport systems and enable BBB crossing, thereby boosting therapeutic efficacy. Lipid-based nanoparticles (LNPs), such as liposomes, niosomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs), are among the most promising delivery systems due to their unique properties, including their size, surface modification capabilities, and proven biosafety. Additionally, inorganic nanoparticles such as gold nanoparticles, mesoporous silica, superparamagnetic iron oxide nanoparticles, and dendrimers offer promising alternatives. Inorganic nanoparticles (INPs) can be easily engineered, and their surfaces can be modified with various elements or biological ligands to enhance BBB penetration, targeted delivery, and biocompatibility. Strategies such as surface engineering and functionalization have been employed to ensure biocompatibility and reduce cytotoxicity, making these nanoparticles safer for clinical applications. The use of INPs in GBM treatment has shown promise in improving the efficacy of traditional therapies like chemotherapy, radiotherapy, and gene therapy, as well as advancing newer treatment strategies, including immunotherapy, photothermal and photodynamic therapies, and magnetic hyperthermia. This article reviews the latest research on lipid and inorganic nanoparticles in treating GBM, focusing on active and passive targeting approaches. Full article

Urothelial carcinoma (UC) is the most common histological subtype of bladder tumors; however, bladder cancer represents a heterogeneous group of diseases with at least 40 distinct histological subtypes. Among these, the 2022 World Health Organization classification of urinary tract tumors identifies a range of less common subtypes of invasive UC, formerly known as variants, which are considered high-grade tumors, including squamous cell, small-cell, sarcomatoid urothelial, micropapillary, plasmacytoid, and urachal carcinomas, and adenocarcinoma. Their accurate histological diagnosis is critical for risk stratification and therapeutic decision-making, as most subtype histologies are associated with poorer outcomes than conventional UC. Despite the importance of a precise diagnosis, high-quality evidence on optimal treatments for subtype histologies remains limited owing to their rarity. In particular, neoadjuvant and adjuvant chemotherapy have not been well characterized, and prospective data are scarce. For advanced-stage diseases, clinical trial participation is strongly recommended to address the lack of robust evidence. Advances in molecular pathology and the development of targeted therapies and immunotherapies have reshaped our understanding and classification of bladder cancer subtypes, spurring efforts to identify predictive biomarkers to guide personalized treatment strategies. Nevertheless, the management of rare bladder cancer subgroups remains challenging because they are frequently excluded from clinical trials. For localized disease, curative options such as surgical resection or radiotherapy are available; however, treatment options become more limited in recurrence or metastasis, where systemic therapy is primarily used to control disease progression and palliate symptoms. Herein, we present recent advances in the management of urothelial and non-urothelial bladder cancer subtypes and also explore the current evidence guiding their treatment and emphasize the challenges and perspectives of future therapeutic strategies. Full article

Exosomes are small extracellular vesicles and are crucial in intercellular communication. Interestingly, tumor-derived exosomes carry oncogenic molecules, such as proteins and microRNAs, which can reprogram recipient cells, promote angiogenesis, and stimulate cancer pre-metastatic niche, supporting cancer growth and metastasis. On the other hand, their biocompatibility, stability, and ability to cross biological barriers make them attractive candidates for drug delivery. Recent advances have shown the potential for exosomes to be used in early disease detection and in targeted drug therapy by delivering therapeutic agents specifically to tumor sites. Despite the promising applications, a number of challenges remain, including exosome isolation and characterization, as well as their inherent heterogeneity. Thus, the current review aims to describe the roles of exosomes in health and disease, and discuss the challenges that hinder their development into becoming useful medical tools. Full article

Background: Immunosenescence is the aging of the immune system, which is closely related to the development and prognosis of lung cancer. Targeting immunosenescence is considered a promising therapeutic approach. Methods: We defined an immunosenescence gene set (ISGS) and examined it across 33 TCGA tumor types and 29 GTEx normal tissues. We explored the 46,993 single cells of two lung cancer datasets. The immunosenescence risk model (ISRM) was constructed in TCGA LUAD by network analysis, immune infiltration analysis, and lasso regression and validated by survival analysis, cox regression, and nomogram in four lung cancer cohorts. The predictive ability of ISRM for drug response and immunotherapy was detected by the oncopredict algorithm and XGBoost model. Results: We found that senescent lung tissues were significantly enriched in ISGS and revealed the heterogeneity of immunosenescence in pan-cancer. Single-cell and bulk transcriptomics characterized the distinct immune microenvironment between old and young lung cancer. The ISGS network revealed the crucial function modules and transcription factors. Multiplatform analysis revealed specific associations between immunosenescence and the tumor progression of lung cancer. The ISRM consisted of five risk genes (CD40LG, IL7, CX3CR1, TLR3, and TLR2), which improved the prognostic stratification of lung cancer across multiple datasets. The ISRM showed robustness in immunotherapy and anti-tumor therapy. We found that lung cancer patients with a high-risk score showed worse survival and lower expression of immune checkpoints, which were resistant to immunotherapy. Conclusions: Our study performed a comprehensive framework for assessing immunosenescence levels and provided insights into the role of immunosenescence in cancer prognosis and biomarker discovery. Full article

In recent years, awareness regarding micro-nanoplastics’ (MNPs) potential effects on human health has progressively increased. Despite a large body of evidence regarding the origin and distribution of MNPs in the environment, their impact on human health remains to be determined. In this context, there is a major need to address their potential carcinogenic risks, since MNPs could hypothetically mediate direct and indirect carcinogenic effects, the latter mediated by particle-linked chemical carcinogens. Currently, evidence in this field is scarce and heterogeneous, but the reported increased incidence of malignant tumors among younger populations, together with the ubiquitous environmental abundance of MNPs, are rising a global concern regarding the possible role of MNPs in the development and progression of cancer. In this review, we provide an overview of the currently available evidence in eco-toxicology, as well as methods for the identification and characterization of environmental MNP particulates and their health-associated risks, with a focus on cancer. In addition, we suggest possible routes for future research in order to unravel the carcinogenetic potential of MNP exposure and to understand prognostic and preventive implications of intratumoral MNPs. Full article

Magnetic resonance imaging (MRI) currently serves as the primary diagnostic method for glioma detection and monitoring. The integration of neurosurgery, radiation therapy, pathology, and radiology in a multi-disciplinary approach has significantly advanced its diagnosis and treatment. However, the prognosis remains unfavorable due to treatment resistance, inconsistent response rates, and high recurrence rates after surgery. These factors are closely associated with the complex molecular characteristics of the tumors, the internal heterogeneity, and the relevant external microenvironment. The complete removal of gliomas presents challenges due to their infiltrative growth pattern along the white matter fibers and perivascular space. Therefore, it is crucial to comprehensively understand the molecular features of gliomas and analyze the internal tumor heterogeneity in order to accurately characterize and quantify the tumor invasion range. The multi-parameter quantitative MRI technique provides an opportunity to investigate the microenvironment and aggressiveness of glioma tumors at the cellular, blood perfusion, and cerebrovascular response levels. Therefore, this review examines the current applications of advanced multi-parameter quantitative MRI in glioma research and explores the prospects for future development. Full article

Background/Objectives: Salivary gland carcinomas encompass a broad group of malignant lesions characterized by varied prognoses. Stem cells have been associated with the potential for self-renewal and differentiation to various subpopulations, resulting in histopathological variability and diverse biological behavior, features that characterize salivary gland carcinomas. This study aims to provide a thorough systematic review of immunohistochemical studies regarding the expression and prognostic significance of stem cell markers between different malignant salivary gland tumors (MSGTs). Methods: The English literature was searched via the databases MEDLINE/PubMed, EMBASE via OVID, Web of Science, Scopus, and CINHAL via EBSCO. The Joanna Briggs Institute Critical Appraisal Tool was used for risk of bias (RoB) assessment. Meta-analysis was conducted for markers evaluated in the same pair of diseases in at least two studies. Results: Fifty-four studies reported the expression of stem cell markers, e.g., c-KIT, CD44, CD133, CD24, ALDH1, BMI1, SOX2, OCT4, and NANOG, in various MSGTs. Low, moderate, and high RoB was observed in twenty-five, eleven, and eighteen studies, respectively. Meta-analysis revealed an outstanding discriminative ability of c-KIT for adenoid cystic carcinoma (AdCC) over polymorphous adenocarcinoma [P(LG)A] but did not confirm the prognostic significance of stem cell markers in MSGTs. Conclusions: This study indicated a possible link between stem cells and the histopathological heterogeneity and diverse biological behavior that characterize the MSGTs. c-KIT might be of diagnostic value in discriminating between AdCC and P(LG)A. Full article

Background: Salvage treatment options have not been validated in relapsed or refractory germ cell tumors. Moreover, the study populations including these patients have different heterogeneities. This study aimed to evaluate the efficacy and safety of three cycles of TIP sequential high-dose chemotherapy in patients with testicular non-seminomatous germ cell tumors who relapsed or had a refractory course after first-line platinum-based chemotherapy. Methods: Data of 141 patients who underwent three cycles of TIP followed by HDCT due to relapsed/refractory gonadal NSGCTs after first-line cisplatin-based chemotherapy (BEP/EP) at Gulhane School of Medicine Hospital Medical Oncology Department between January 2017 and May 2024 were evaluated retrospectively. Patients underwent a treatment regimen consisting of two phases. Initially, they received three cycles of induction therapy using a combination known as TIP, which includes paclitaxel, ifosfomide, and cisplatin. Following this, they were given a single cycle of high-dose chemotherapy. Demographic and clinicopathological features of patients and treatment-related complications and survival outcomes were recorded. Results: Median follow-up for all patients was 35.2 (95% CI, 29.45 to 41.07) months. Complete Response (CR) or marker negative Partial Response (PR) after HDCT was achieved in 84 (59.6%) patients. Median time for PFS not reached (NR) (95% CI, NR) in the entire group. The 2-year PFS rate was 51.8%. Median time for OS not reached (95% CI, NR) and the 2-year OS rate was 72.3%. The most common myelotoxicity observed after HDCT until engraftment was grade 4 neutropenia (100%) and grade 4 thrombocytopenia (96.5%). Transplantation-related mortality occurred in 7.1% of patients. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis for overall survival were platinum refractory disease and AFP and/or beta HCG elevation. Conclusions: Significant survival can be achieved after three cycles of TIP consecutive HDCT, while treatment-related mortality was found to be low. Full article

Prostate cancer (PCa) remains a critical global health challenge, with high mortality rates and significant heterogeneity, particularly in advanced stages. While early-stage PCa is often manageable with conventional treatments, metastatic PCa is notoriously resistant, highlighting an urgent need for precise biomarkers and innovative therapeutic strategies. This review focuses on the dualistic roles of sirtuins, a family of NAD+-dependent histone deacetylases, dissecting their unique contributions to tumor suppression or progression in PCa depending on the cellular context. It reveals their multifaceted impact on hallmark cancer processes, including sustaining proliferative signaling, evading growth suppressors, activating invasion and metastasis, resisting cell death, inducing angiogenesis, and enabling replicative immortality. SIRT1, for example, fosters chemoresistance and castration-resistant prostate cancer through metabolic reprogramming, immune modulation, androgen receptor signaling, and enhanced DNA repair. SIRT3 and SIRT4 suppress oncogenic pathways by regulating cancer metabolism, while SIRT2 and SIRT6 influence tumor aggressiveness and androgen receptor sensitivity, with SIRT6 promoting metastatic potential. Notably, SIRT5 oscillates between oncogenic and tumor-suppressive roles by regulating key metabolic enzymes; whereas, SIRT7 drives PCa proliferation and metabolic stress adaptation through its chromatin and nucleolar regulatory functions. Furthermore, we provide a comprehensive summary of the roles of individual sirtuins, highlighting their potential as biomarkers in PCa and exploring their therapeutic implications. By examining each of these specific mechanisms through which sirtuins impact PCa, this review underscores the potential of sirtuin modulation to address gaps in managing advanced PCa. Understanding sirtuins’ regulatory effects could redefine therapeutic approaches, promoting precision strategies that enhance treatment efficacy and improve outcomes for patients with aggressive disease. Full article

Glioblastoma (GBM) is a primary central nervous system malignancy with a median survival of 15–20 months. The presence of both intra- and intertumoral heterogeneity limits understanding of biological mechanisms leading to tumor resistance, including immune escape. An attractive field of research to examine treatment resistance are immune signatures composed of cluster of differentiation (CD) markers and cytokines. CD markers are surface markers expressed on various cells throughout the body, often associated with immune cells. Cytokines are the effector molecules of the immune system. Together, CD markers and cytokines can serve as useful biomarkers to reflect immune status in patients with GBM. However, there are gaps in the understanding of the intricate interactions between GBM and the peripheral immune system and how these interactions change with standard and immune-modulating treatments. The key to understanding the true nature of these interactions is through multi-omic analysis of tumor progression and treatment response. This review aims to identify potential non-invasive blood-based biomarkers that can contribute to an immune signature through multi-omic approaches, leading to a better understanding of immune involvement in GBM. Full article

In the field of digestive system tumor research, spatial transcriptomics technologies are used to delve into the spatial structure and the spatial heterogeneity of tumors and to analyze the tumor microenvironment (TME) and the inter-cellular interactions within it by revealing gene expression in tumors. These technologies are also instrumental in the diagnosis, prognosis, and treatment of digestive system tumors. This review provides a concise introduction to spatial transcriptomics and summarizes recent advances, application prospects, and technical challenges of these technologies in digestive system tumor research. This review also discusses the importance of combining spatial transcriptomics with single-cell RNA sequencing (scRNA-seq), artificial intelligence, and machine learning in digestive system cancer research. Full article

Breast cancer (BC) is one of the most prevalent forms of cancer globally, and has recently become the leading cause of cancer-related mortality in women. BC is a heterogeneous disease comprising various histopathological and molecular subtypes with differing levels of malignancy, and each patient has an individual prognosis. Etiology and pathogenesis are complex and involve a considerable number of genetic alterations and dozens of alterations in non-coding RNA expression. Non-coding RNAs are part of an abundant family of single-stranded RNA molecules acting as key regulators in DNA replication, mRNA processing and translation, cell differentiation, growth, and overall genomic stability. In the context of breast cancer, non-coding RNAs are involved in cell cycle control and tumor cell migration and invasion, as well as treatment resistance. Alterations in non-coding RNA expression may contribute to the development and progression of breast cancer, making them promising biomarkers and targets for novel therapeutic approaches. Currently, the use of non-coding RNAs has not yet been applied to routine practice; however, their potential has been very well studied. The present review is a literature overview of current knowledge and its objective is to delineate the function of diverse classes of non-coding RNAs in breast cancer, with a particular emphasis on their potential utility as diagnostic and prognostic markers or as therapeutic targets and tools. Full article

Canine high-grade glioma (HGG) is among the deadliest and most treatment-resistant forms of canine cancer. Successful, widespread treatment is challenged by heterogeneity in tumor cells and the tumor microenvironment and tumor evolution following treatment. Immunotherapy is theoretically a strong novel therapy, since HGG-generated immunosuppression is a substantial malignancy mechanism. Immunotherapy has improved survival times overall, but has been associated with extremely poor outcomes in French bulldogs. Given this breed-specific observation, we hypothesized that within the French bulldog breed, there are key transcriptomic differences when compared to other breeds, and that their tumors change differently in response to immunotherapy. Using bulk RNA sequencing, French bulldog tumors were confirmed to differ substantially from boxer and Boston terrier tumors, with only 15.9% overlap in significant differentially expressed genes (DEGs). In upregulated DEGs, the magnitude of changes in expression post-treatment compared to pre-treatment was markedly greater in French bulldogs. Gene set enrichment analysis confirmed that following treatment, French bulldog tumors showed enrichment of key immune-associated pathways previously correlated with poor prognosis. Overall, this study confirmed that French bulldog HGG transcriptomes differ from boxer and Boston terrier transcriptomes, further refining description of the canine glioma transcriptome and providing important information to guide novel therapy development, both for specific dog breeds and for possible correlative variants of human glioblastoma. Full article

In the present study, we aimed to investigate intratumoral karyotype diversity as well as the estrogen/progesterone effect on the cytogenetic profile of uterine leiomyomas (ULs). A total of 15 UL samples obtained from 15 patients were cultured in the media supplemented with estrogen and/or progesterone and without adding hormones. Conventional cytogenetic analysis of culture samples revealed clonal chromosomal abnormalities in 11 out of 15 ULs. Cytogenetic findings were presented by simple and complex chromosomal rearrangements (64% and 36% of cases, respectively) verified through FISH and aCGH. In most ULs with complex chromosomal rearrangements, the breakpoints did not feature clusterization on a single chromosome but were evenly distributed across rearranged chromosomes. The number of breakpoints showed a strong positive correlation with the number of rearranged chromosomes. Moreover, both abovementioned parameters were in a linear dependency from the number of karyotypically different clones per UL. This suggests that complex chromosomal rearrangements in ULs predominantly originate through sequential events rather than one hit. The results of UL cytogenetic analysis depended on the presence of estrogen and/or progesterone in the culture medium. The greatest variety of cytogenetically different cell clones was detected in the samples cultured without hormone supplementation. Their counterparts cultured with progesterone supplementation showed a sharp decrease in clone number, whereas such a decrease induced by estrogen or estrogen–progesterone supplementation was insignificant. These findings suggest that estrogen–progesterone balance is crucial for forming a UL cytogenetic profile, which, in turn, may underlie the unique response of the every karyotypically abnormal UL to medications. Full article