Search Results (5,857)

Basal cell carcinoma (BCC) is the most common skin cancer, predominantly affecting sun-exposed areas. It typically grows slowly and rarely metastasizes, though untreated cases can cause significant tissue destruction and morbidity. Its pathogenesis primarily involves dysregulation of the Hedgehog (HH) signaling pathway, mainly through mutations in PTCH1 or SMO genes, leading to chronic activation of downstream GLI transcription factors. Accordingly, current targeted therapies for locally advanced, unresectable, or metastatic BCC focus on SMO inhibition, using orally administered drugs such as vismodegib and sonidegib. Although these therapies have shown success, many patients develop resistance, with about 50% harboring mutated SMO. In numerous cases, genetic determinants (sometimes pre-existing) of resistance remain unidentified, complicating patient management. Here, we report a case of a 58-year-old female with advanced BCC who initially exhibited a favorable response to sonidegib but developed resistance after approximately one year. This resistance was not attributable to the acquired mutations in SMO but rather to intra-tumor heterogeneity and additional mutations in critical driver genes, including TP53, APC, FGFR1 and NOTCH1, which likely enable HH pathway inhibition. To our knowledge, this is the first report documenting a sonidegib resistance mechanism in BCC that is independent of HH pathway mutations. This case highlights the complexity of resistance mechanisms to HH inhibitors and underscores the critical need for comprehensive molecular tumor profiling prior to initiating targeted therapy. Full article

Colorectal cancer (CRC) remains a major cause of morbidity and mortality worldwide, with its incidence and biological behavior influenced by both genetic and environmental factors. Emerging evidence highlights notable sex differences in CRC, with men generally exhibiting higher incidence rates and poorer prognoses, while women often display stronger immune responses and distinct molecular profiles. Traditional screening tools, such as colonoscopy and fecal-based tests, have improved survival through early detection but are limited by invasiveness, cost, and adherence issues. In this context, biosensors have emerged as innovative diagnostic platforms capable of rapid, sensitive, and non-invasive detection of CRC-associated biomarkers, including genetic, epigenetic, and metabolic alterations. These technologies integrate biological recognition elements with nanomaterials, microfluidics, and digital systems, enabling the analysis of biomarkers such as proteins, nucleic acids, autoantibodies, epigenetic marks, and metabolic or VOC signatures from blood, stool, or breath and supporting point-of-care applications. Electrochemical, optical, piezoelectric, and FET platforms enable label-free or ultrasensitive multiplexed readouts and align with liquid biopsy workflows. Despite challenges related to standardization, robustness in complex matrices, and clinical validation, advances in nanotechnology, multi-analyte biosensing with artificial intelligence are enhancing biosensor performance. Integrating biosensor-based diagnostics with knowledge of sex-specific molecular and hormonal pathways may lead to more precise and equitable approaches in CRC detection, selection of therapeutic regimes and management. Full article

Background/Objectives: Colorectal cancer (CRC) is the second most common cause of cancer death worldwide. Evidence suggests that a polyphenol-rich diet may lower the risk of CRC. The aim of this study was to demonstrate the potential antitumor effects of a flavonoid-rich extract of bergamot juice (BJe) in both in vitro and in vivo CRC models, assessing the underlying mechanisms. Methods: CRC cells, among which HCT-116, have been employed to assess the fine mechanism of action of BJe, whereas a mouse model of azoxymethane (AOM)-induced CRC was exploited to appreciate the anti-cancer effects of BJe. Results: BJe inhibited the growth of several CRC cells, especially HCT-116. In this cell line, BJe induced apoptosis and blocked the cell cycle in the G1 phase, as well as modulated the gene expression of apoptosis- and cell cycle-related factors. Moreover, BJe prompted reactive oxygen species production and impaired mitochondrial membrane potential. In the nucleus of these cancerous cells, BJe induced DNA damage as confirmed by the raised levels of 8-oxo-2′-deoxyguanosine and phosphorylation of histone H2A.X. In mice with AOM-induced CRC, BJe was able to lower the number of aberrant crypt foci. Moreover, BJe reduced the percentage of mice bearing both polyps and tumors, as well as their number. Conclusions: Our study supports the role of BJe against CRC, providing knowledge on the underlying mechanism of action. Full article

Background/Objectives: Among survivors of cancer diagnosed in childhood, adolescence, or young adulthood (C-AYAs), cardiotoxic therapies combined with acquired cardiovascular risk factors (CVRFs) increase the risk for cardiovascular events. To our knowledge, no prior analysis has examined CVRFs among C-AYAs < 20 years old or compared CVRFs among younger and older C-AYAs. Methods: In this single-center study, individuals diagnosed with cancer at ≤39 years, treated with anthracycline-based chemotherapy (2010–2023), and with a post-treatment lipid panel and ≥2 post-treatment ambulatory blood pressure measurements were included. The CVRF prevalence was assessed among C-AYAs < 20 and ≥20 years old, using age-appropriate AAP and ACC/AHA guidelines. These prevalences were compared with the ICD-9/10 code prevalence. The prescription of medications with antihypertensive effects (MAHEs) and lipid-lowering therapy was assessed. Results: Among 276 C-AYAs, the median age was 28.1 years (IQR 18.1–38.3) at dyslipidemia screening and 29.3 (IQR 20.0–38.7) at hypertension screening. Dyslipidemia was present in 52.9% (146/276) and hypertension in 56.2% (155/276) of C-AYAs. C-AYAs < 20 years old had a high prevalence of dyslipidemia, 51.7% (45/87), and hypertension, 31.9% (29/91). CVRFs were frequently underdiagnosed, particularly dyslipidemia, among C-AYAs < 20 years old, with only 12.6% (11/87) having a diagnosis via the ICD code. C-AYAs < 20 years old with diagnoses of dyslipidemia and hypertension were significantly less likely to receive lipid-lowering therapy (2.2% vs. 14.9%) and trended toward less MAHEs (13.8% vs. 31.0%) compared to C-AYAs ≥ 20. Conclusions: Among C-AYAs treated with anthracyclines, dyslipidemia and hypertension were highly prevalent even at a young age (<20 years). Younger survivors with dyslipidemia and hypertension were less frequently prescribed lipid-lowering therapy or MAHEs. Full article

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality, with inflammation playing a pivotal role in its pathogenesis. Chronic inflammation in the intestine significantly increases the risk of CRC development. Main compounds participating in the inflammatory process are prostaglandins; bioactive lipids derived from arachidonic acid metabolism via the cyclooxygenase (COX) pathway. While it is well known that prostaglandin E₂ (PGE₂) promotes CRC tumorigenesis, other prostaglandins, such as PGD₂, PGF_2α, and prostacyclin (PGI₂), remain relatively underexplored. These prostaglandins may exert distinct or opposing effects on CRC development, but the current understanding of their functions is limited. Additionally, the impact of prostaglandins on immune regulation and the tumor microenvironment, is far from being fully understood. Addressing these knowledge gaps is crucial for identifying novel therapeutic targets and optimizing chemoprevention strategies. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of CRC, largely by inhibiting prostaglandin producing enzymes. However, their use is limited due to their gastrointestinal and cardiovascular side effects. Therefore, understanding the intricate role of inflammation and prostaglandin signaling in CRC is critical to develop safer and more effective chemopreventive approaches. This review summarizes the current knowledge of prostaglandins, linking inflammation and CRC. It further addresses the potential of targeting prostaglandin pathways for chemoprevention. Furthermore, we discuss emerging pharmacological targets that modulate prostaglandin production, signaling or degradation, offering promise for preventing CRC development. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease worldwide. It greatly increases hepatic cirrhosis and cancer, cardiovascular disease, and chronic kidney disease. Despite the rising frequency of MASLD in Saudi Arabia, public understanding of its management is lacking. Objective: This study seeks to evaluate public knowledge, attitudes, and management barriers related to MASLD, thereby informing future educational and preventive strategies. Methods: A cross-sectional study was conducted from November 2023 to October 2024, involving 502 participants across Saudi Arabia, employing a modified self-administered online questionnaire. Data was analyzed using SPSS 25. Descriptive statistics and Chi-square tests were used to investigate correlations between knowledge or attitude levels and demographics, with a significance threshold of p < 0.05. Results: Less than half of the respondents who took part (47.2%) had heard of MASLD. Of them, 24.9% had good knowledge, 38.2% had fair knowledge, and 36.9% had low understanding. There were strong links between knowledge and age, education, and job status, but not between knowledge and gender (p = 0.514). People were somewhat aware that being overweight (48.4%) and having high cholesterol (51.8%) were risk factors, but they often had wrong ideas regarding diabetes and high blood pressure. Only 7.8% of those surveyed said they had been formally diagnosed, and 74.4% of those who had been were given advice on how to change their lifestyle. Barriers to management included the idea that lifestyle change alone suffices (46.7%), the absence of medical advice (46.7%), and insufficient disease awareness (33.3%). Conclusions: The research shows that many Saudis are unaware of MASLD and have misconceptions about it. Targeted health education programs, greater provider–patient communication, and primary care MASLD knowledge are needed to close these gaps and promote disease prevention and management. Full article

T cells and B cells are central components of the adaptive immune system, orchestrating immune responses through a complex network of interactions. This review explores the dynamic interplay between T and B cells, focusing on their development, activation, and functional coordination in immune defense. T cells provide essential help to B cells through cytokine signaling and direct cell–cell interactions, facilitating antibody production and affinity maturation in germinal centers. Conversely, B cells contribute to antigen presentation and cytokine modulation, influencing T cell differentiation and function. The regulation of these interactions is critical for maintaining immune homeostasis, preventing autoimmunity, and enhancing vaccine efficacy. Dysregulation of T-B cell crosstalk is implicated in various immune disorders, including autoimmune diseases and immunodeficiencies. Recent advances in immunotherapy have targeted these pathways to modulate immune responses in conditions such as cancer, infections, and inflammatory diseases. This review synthesizes current knowledge on T and B cell physiology, highlighting emerging research on their cooperative mechanisms. Full article

Glioblastoma (GBM) is one of the most common and aggressive primary malignant tumors of the central nervous system, accounting for about half of all gliomas in adults. Despite intensive research and advances in molecular biology, genomics, and modern neuroimaging techniques, the prognosis for patients with GBM remains extremely poor. Despite the implementation of multimodal treatment involving surgery, radiotherapy, and chemotherapy with temozolomide, the average survival time of patients is only about 15 months. This is primarily due to the complex biology of this cancer, which involves numerous genetic and epigenetic abnormalities, as well as a highly heterogeneous tumor structure and the presence of glioblastoma stem cells with self renewal capacity. Mutations and abnormalities in genes such as IDH-wt, EGFR, PTEN, TP53, TERT, and CDKN2A/B are crucial in the pathogenesis of GBM. In particular, IDH-wt status (wild-type isocitrate dehydrogenase) is one of the most important identification markers distinguishing GBM from other, more favorable gliomas with IDH mutations. Frequent EGFR amplifications and TERT gene promoter mutations lead to the deregulation of tumor cell proliferation and increased aggressiveness. In turn, the loss of function of suppressor genes such as PTEN or CDKN2A/B promotes uncontrolled cell growth and tumor progression. The immunosuppressive tumor microenvironment also plays an important role, promoting immune escape and weakening the effectiveness of systemic therapies, including immunotherapy. The aim of this review is to summarize the current state of knowledge on the epidemiology, classification, pathogenesis, diagnosis, and treatment of glioblastoma multiforme, as well as to discuss the impact of recent advances in molecular and imaging diagnostics on clinical decision-making. A comprehensive review of recent literature (2018–2025) was conducted, focusing on WHO CNS5 classification updates, novel biomarkers (IDH, TERT, MGMT, EGFR), and modern diagnostic techniques such as liquid biopsy, radiogenomics, and next-generation sequencing (NGS). The results of the review indicate that the introduction of integrated histo-molecular diagnostics in the WHO 2021 classification has significantly increased diagnostic precision, enabling better prognostic and therapeutic stratification of patients. Modern imaging techniques, such as advanced magnetic resonance imaging (MRI), positron emission tomography (PET), and radiomics and radiogenomics tools, allow for more precise assessment of tumor characteristics, prediction of response to therapy, and monitoring of disease progression. Contemporary molecular techniques, including DNA methylation profiling and NGS, enable in-depth genomic and epigenetic analysis, which translates into a more personalized approach to treatment. Despite the use of multimodal therapy, which is based on maximum safe tumor resection followed by radiotherapy and temozolomide chemotherapy, recurrence is almost inevitable. GBM shows a high degree of resistance to treatment, which results from the presence of stem cell subpopulations, dynamic clonal evolution, and the ability to adapt to unfavorable microenvironmental conditions. Promising preclinical and early clinical results show new therapeutic strategies, including immunotherapy (cancer vaccines, checkpoint inhibitors, CAR-T therapies), oncolytic virotherapy, and Tumor Treating Fields (TTF) technology. Although these methods show potential for prolonging survival, their clinical efficacy still needs to be confirmed in large studies. The role of artificial intelligence in the analysis of imaging and molecular data is also increasingly being emphasized, which may contribute to the development of more accurate predictive models and therapeutic decisions. Despite these advancements, GBM remains a major therapeutic challenge due to its high heterogeneity and treatment resistance. The integration of molecular diagnostics, artificial intelligence, and personalized therapeutic strategies that may enhance survival and quality of life for GBM patients. Full article

In the digital age, online industry documents have become an available and abundant source to inform qualitative health research on the commercial determinants of health (CDOH), including how corporations shape knowledge, policy, and public perception to protect business interests. This paper introduces the situational scoping method, a rigorous and transparent qualitative approach rooted in critical constructivism designed to conduct an overview of large databases of industry documents and systematically map industry responses to external events perceived as threats or opportunities. Developed through a pilot study on environmental exposures and breast cancer, using the UCSF Industry Documents Library, the method consists of three stages: (1) identification of a broad range of external events over time perceived by industries as a threat or opportunity to business interests; (2) selection of a sample of external events for further analysis; and (3) social world/arena mapping of industry responses to selected external events. Conducted by a transdisciplinary team with community partners, the method builds on and enhances traditional tobacco documents and CDOH research by integrating participatory action and collaborative analysis of digital archives. It also offers a transferable framework for examining corporate influence across sectors. This work contributes to emerging public health methodologies that confront commercial power through critical, community-engaged inquiry essential for emancipatory action. Full article

Human Papillomavirus (HPV)-related cancers constitute a major global health problem, accounting for 4.5% of all human cancers. Studying the composition of the tumor microenvironment (TME) of HPV-related cancers may help develop therapeutic strategies or identify prognostic biomarkers with potential clinical significance. Among all the components of TME, mast cells (MCs) appear to be particularly relevant in HPV-related tumors. MCs are myeloid-derived immune cells that release a wide range of inflammatory mediators. It is now recognized that these immune cells are important players within the TME, where they can exert both anti- and pro-tumor activities depending on the type of MC-derived inflammatory mediators released. MCs may play an important role in the processes associated with cell transformation, development, and the progression of HPV-associated tumors; however, their specific functions in these neoplasms are not yet fully understood. This review addresses the current state of knowledge on MCs and their contribution to the molecular biology of HPV-related cancers. In addition, it highlights MCs’ roles in the pro- or anti-tumor paradigm and discusses their emerging potential as therapeutic targets or prognostic biomarkers. Full article

Physical exercise is a potent non-pharmacological strategy for the prevention and management of chronic non-communicable diseases (NCDs), including type 2 diabetes, cardiovascular diseases, obesity, and certain cancers. Growing evidence demonstrates that the benefits of exercise extend beyond its physiological effects and are largely mediated by coordinated molecular and cellular adaptations. This review synthesizes current knowledge on the key mechanisms through which exercise modulates metabolic health, emphasizing intracellular signaling pathways, epigenetic regulation, and myokine-driven inter-organ communication. Exercise induces acute and chronic activation of pathways such as AMPK, PGC-1α, mTOR, MAPKs, and NF-κB, leading to enhanced mitochondrial biogenesis, improved oxidative capacity, refined energy sensing, and reduced inflammation. Additionally, repeated muscle contraction stimulates the release of myokines—including IL-6, irisin, BDNF, FGF21, apelin, and others—that act through endocrine and paracrine routes to regulate glucose and lipid metabolism, insulin secretion, adipose tissue remodeling, neuroplasticity, and systemic inflammatory tone. Epigenetic modifications and exercise-responsive microRNAs further contribute to long-term metabolic reprogramming. Collectively, these molecular adaptations establish exercise as a systemic biological stimulus capable of restoring metabolic homeostasis and counteracting the pathophysiological processes underlying NCDs. Understanding these mechanisms provides a foundation for developing targeted, personalized exercise-based interventions in preventive and therapeutic medicine. Full article

Triple-negative breast cancer (TNBC) has the poorest prognosis among all breast cancer subtypes, largely due to the lack of targeted therapies and its resistance to both chemotherapy and immunotherapy. A deeper understanding of TNBC biology is therefore critical for identifying therapeutic targets. Molecular subtyping of TNBC, first introduced over a decade ago, has significantly advanced our knowledge of the disease’s biology. However, tumor heterogeneity remains a major factor contributing to poor clinical outcomes and treatment resistance. The integration of multiomic technologies, including genomic, transcriptomic, proteomic, and metabolomic analyses, offers a powerful approach to further dissect tumor heterogeneity and accelerate the discovery of new biomarkers and therapeutic targets. This review aims to highlight the potential utility and evolving role of multiomics (-omics) in improving our understanding of TNBC biology—particularly tumor heterogeneity—ultimately facilitating the development of novel therapies and actionable strategies to treat the disease. Full article

The tumour suppressor TP53 (tumor protein p53) is a master regulator of cell cycle, DNA repair, and apoptosis, and its mutation is a hallmark of cancer, with individual mutations exerting distinct effects on tumour biology. Despite accounting for ~7% of all TP53 variants, splice site mutations remain the least studied class, and their functional and clinical consequences are poorly understood. We analyzed 25,058 TP53 variants (18,562 somatic; 6496 germline) to characterize the frequency, molecular impact, transcriptional effects, genomic instability, and clinical outcomes of splice mutations. These alterations showed distinct distributions and substitution patterns between germline and somatic contexts and were frequently associated with copy number alterations, reduced TP53 mRNA, and variable protein expression. Transcriptomic profiling identified two transcriptional phenotypes: one with global suppression of canonical p53 target genes and another with mixed activation and repression independent of tumour type. Genomic instability was elevated in a subset of splice-mutant tumours, correlating with increased relapse risk, while other splice mutations showed lower instability but divergent clinical outcomes, including unexpectedly poor prognoses. Our findings fill a critical knowledge gap, defining the biological and clinical spectrum of TP53 splice site mutations and highlighting their potential as prognostic biomarkers and therapeutic targets in precision oncology. Full article

Poly (lactic-co-glycolic acid) (PLGA) is a widely used copolymer with applications across medical, pharmaceutical, and other industrial fields. Its biodegradability and biocompatibility make it one of the most versatile polymers for nanoscale drug delivery. The present review addresses current knowledge and recent advances in PLGA-based co-delivery nanoformulations with a special reference to design strategies, functional mechanisms, and translational potential. Conventional and advanced fabrication methods, the structural design of PLGA-based nanocarriers, approaches to scale-up and reproducibility, classification of co-delivery types, mechanisms governing drug release, surface modification and functionalization are all discussed. Special attention is given to PLGA-based co-delivery systems, encompassing drug–drug, drug–gene, gene–gene and multi-modal combinations, supported by recent studies demonstrating synergistic therapeutic outcomes. The review also examines clinical translation efforts and the regulatory landscape for PLGA-based nanocarriers. Unlike most existing reviews that typically focus either on PLGA fundamentals or on co-delivery approaches in isolation, this article bridges these domains by providing an integrated, comparative analysis of PLGA-based co-delivery systems and elucidating a critical gap in linking design strategies with translational requirements. In addition, by emphasising the relevance of PLGA-based co-delivery for combination therapies, particularly in cancer and other complex diseases, the review highlights the strong clinical and translational potential of these platforms. Key challenges, such as reproducibility, large-scale manufacturing, and complex regulatory pathways, are discussed alongside emerging trends and future perspectives. Taken together, this review positions PLGA-based co-delivery strategies as a critical driver for advancing precision therapeutics and shaping the future landscape of nanomedicine. Full article

Breast cancer is a substantial and growing public health issue in India, with epidemiological data demonstrating distinct and often severe disease characteristics in contrast to Western countries. Contrary to the global trend, Indian women frequently develop the disease at an earlier age and tend to present with more advanced stages, emphasizing important variations in disease pathophysiology. This review compiles and critically evaluates the current literature to describe the specific pathophysiology of breast cancer in the Indian population. We investigate the unique cellular and molecular landscapes, evaluate the impact of specific Indian demographic and genetic features, and highlight crucial gaps in knowledge, diagnostic tools, and therapeutic approaches. The assessment reveals a molecular landscape determined by the incidence of specific tumor subtypes; triple-negative breast cancer, for instance, is frequently diagnosed in younger women, and genetic profiling research suggests variations in its susceptibility genes and mutation patterns when compared to global populations. While this paper brings together recent advancements, it highlights the challenges of adopting global diagnostic and treatment guidelines in the Indian healthcare system. These challenges are largely due to variances and specific demographic and socioeconomic discrepancies that create substantial hurdles for timely diagnosis and patient care. We highlight significant gaps, such as the need for more complete multi-omics profiling of Indian patient cohorts, an absence of uniform and readily available screening programs, and shortcomings in healthcare infrastructure and qualified oncology experts. Furthermore, the review highlights the crucial need for therapeutic strategies tailored to the distinct genetic and demographic profiles of Indian breast cancer patients. We present significant strategies for addressing these challenges, with a focus on integrating multi-omics data and clinical characteristics to gain deeper insight into the underlying causes of the disease. Promising avenues include using artificial intelligence and advancements in technology to improve diagnostics, developing indigenous and affordable treatment options, and establishing context-specific research frameworks for the Indian population. This review also underlines the necessity for personalized strategies to improve breast cancer outcomes in India. Full article