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Cancer is a global health challenge with rising incidence and mortality rates, posing significant concerns. The World Health Organization reports cancer as a leading cause of death worldwide, contributing to nearly one in six deaths. Cancer pathogenesis involves disruptions in cellular signaling pathways, resulting in uncontrolled cell growth and metastasis. Among emerging players in cancer biology, Transient Receptor Potential (TRP) channels, notably TRPV1, have garnered attention due to their altered expression in cancer cells and roles in tumorigenesis and progression. TRPV1, also known as the capsaicin receptor, is pivotal in cancer cell death and pain mediation, offering promise as a therapeutic target. Activation of TRPV1 triggers calcium influx and affects cell signaling linked to growth and death. Additionally, TRPV1 is implicated in cancer-induced pain and chemo-sensitivity, with upregulation observed in sensory neurons innervating oral cancers. Also, when capsaicin, a compound from chili peppers, interacts with TRPV1, it elicits a "hot" sensation and influences cancer processes through calcium influx. Understanding TRPV1's multifaceted roles in cancer may lead to novel therapeutic strategies for managing cancer-related symptoms and improving patient outcomes. The current review elucidates the comprehensive role of capsaicin in cancer therapy, particularly through the TRPV1 channel, highlighting its effects in various cells via different signaling pathways and discussing its limitations. [ABSTRACT FROM AUTHOR]

Background: Lung cancer (LC) is the leading cause of cancer-related deaths. Although low-dose computed tomography (LD-CT) reduces mortality, its clinical use is limited by cost, radiation, and false positives. Therefore, there is an urgent need for non-invasive and cost-effective biomarkers. The Raf Kinase Inhibitor Protein (RKIP) plays a crucial role in cancer development and progression and may also contribute to regulating the tumor–immune system axis. This protein has recently been described in biological fluids. Therefore, we conducted a pilot case–control study to assess RKIP and phosphorylated RKIP (pRKIP) levels in the urine and blood of LC patients. Methods: A novel enzyme linked immunosorbent assay (ELISA) assay was used to measure RKIP and pRKIP levels in urine and blood samples of two cohorts of LC patients and healthy controls (HSs). Furthermore, the biomarkers levels were correlated with tumor characteristics. Results: Serum, but not urine, levels of RKIP were significantly elevated in LC patients, distinguishing them from low- and high-risk healthy subjects with 93% and 74% accuracy, respectively. The RKIP/pRKIP ratio (RpR score) showed an accuracy of 90% and 79% in distinguishing LC patients from HS and HR-HS, respectively. Additionally, the RpR score correlated better with dimension, stage, and lymph node involvement in the tumor group. Conclusions: The serum RKIP and pRKIP profile may be a promising novel biomarker for early-stage LC. [ABSTRACT FROM AUTHOR]

Background/Objectives: Pancreatic cancer remains one of the deadliest malignancies worldwide with a pressing need for early detection and intervention strategies. Emerging evidence has suggested a potential link between pancreas steatosis, characterized by excessive pancreatic fat accumulation, and an increased risk of pancreatic cancer development. This retrospective imaging study aims to elucidate the association between pancreatic steatosis and the subsequent development of pancreatic cancer. In the study, we aimed to determine the characteristics of pancreatic cancer with pancreatic steatosis. Methods: During the period of January 2022 to December 2022, we conducted a retrospective study, collecting 101 newly diagnosed pancreas cancer cases from the available image datasets. A comprehensive database of retrospective abdominal imaging studies, comprising computed tomography (CT) and magnetic resonance imaging (MRI), was established from a diverse patient population and subsequently analyzed. Inclusion criteria encompassed patients having available baseline imaging data, allowing for the assessment of pancreatic fat content. Pancreatic fat content was quantified using validated radiological techniques, while demographic, clinical, and histopathological data were all collected. The clinical data and patient characteristics were collected from medical records and analyzed. Results: Preliminary analysis revealed a significant correlation between elevated pancreatic fat content and an increased incidence of subsequent pancreatic cancer. Moreover, subgroup analysis based on age, gender, and comorbidities provided valuable insight into potential risk factors associated with this progression. Additionally, the study identified novel radiological markers that may serve as early indicators of pancreatic cancer development in individuals with pancreatic steatosis. Conclusions: In the imaging study, approximately 30% (30/101) of pancreatic cancer patients presented with pancreatic steatosis. Chronic pancreatitis emerged as the primary factor contributing to pancreatic steatosis in these patients. Importantly, pancreatic steatosis did not significantly impact the prognosis of pancreatic cancer. Follow-up data revealed no significant differences in survival duration between patients with or without pancreatic steatosis. Additionally, no association was found between pancreatic steatosis and hepatic steatosis. [ABSTRACT FROM AUTHOR]

Wnt signaling is involved in embryo development and cancer. The binding between the DIX domains of Axin1/2, Dishevelled1/2/3, and Coiled-coil-DIX1 is essential for Wnt/β-catenin signaling. Structural and biological studies have revealed that DIX domains are polymerized through head-to-tail interface interactions, which are indispensable for activating β-catenin Wnt signaling. Although different isoforms of Dvl and Axin proteins display both redundant and specific functions in Wnt signaling, the specificity of DIX-mediated interactions remains unclear due to technical challenges. Using AlphaFold2(AF2), we predict the structures of 6 homodimers and 22 heterodimers of DIX domains without templates and compare them with the reported X-ray complex structures. PRODIGY is used to calculate the binding affinities of these DIX complexes. Our results show that the Axin2 DIX homodimer has a stronger binding affinity than the Axin1 DIX homodimer. Among Dishevelled (Dvl) proteins, the binding affinity of the Dvl1 DIX homodimer is stronger than that of Dvl2 and Dvl3. The Coiled-coil-DIX1(Ccd1) DIX homodimer shows weaker binding than the Axin1 DIX homodimer. Generally, heterodimer interactions tend to be stronger than those of homodimers. Our findings provide insights into the mechanism of the Wnt signaling pathway and highlight the potential of AF2 and PRODIGY for studying protein–protein interactions in signaling pathways. [ABSTRACT FROM AUTHOR]

Genomic-oriented oncology has improved tumor classification, treatment options, and patient outcomes. However, genetic heterogeneity, tumor cell plasticity, and the ability of cancer cells to hijack the tumor microenvironment (TME) represent a major roadblock for cancer eradication. Recent biotechnological advances in organotypic cell cultures have revolutionized biomedical research, opening new avenues to explore the use of cancer organoids in functional precision oncology, especially when genomics alone is not a determinant. Here, we outline the potential and the limitations of tumor organoids in preclinical and translational studies with a particular focus on lung cancer pathogenesis, highlighting their relevance in predicting therapy response, evaluating treatment toxicity, and designing novel anticancer strategies. Furthermore, we describe innovative organotypic coculture systems to dissect the crosstalk with the TME and to test the efficacy of different immunotherapy approaches, including adoptive cell therapy. Finally, we discuss the potential clinical relevance of microfluidic mini-organ technology, capable of reproducing tumor vasculature and the dynamics of tumor initiation and progression, as well as immunomodulatory interactions among tumor organoids, cancer-associated fibroblasts (CAFs) and immune cells, paving the way for next-generation immune precision oncology. [ABSTRACT FROM AUTHOR]

The pathogenesis of cancer is complex, involving abnormalities in some genes in organisms. Accurately identifying cancer genes is crucial for the early detection of cancer and personalized treatment, among other applications. Recent studies have used graph deep learning methods to identify cancer driver genes based on biological networks. However, incompleteness and the noise of the networks will weaken the performance of models. To address this, we propose a cancer driver gene identification method based on self-supervision for graph convolutional networks, which can efficiently enhance the structure of the network and further improve predictive accuracy. The reliability of SSCI is verified by the area under the receiver operating characteristic curves (AUROC), the area under the precision-recall curves (AUPRC), and the F1 score, with respective values of 0.966, 0.964, and 0.913. The results show that our method can identify cancer driver genes with strong discriminative power and biological interpretability. [ABSTRACT FROM AUTHOR]

Simple Summary: Metabolic syndrome (MetS), metabolic dysfunction-associated steatotic liver disease (MASLD), and diabetes are all linked to Cholangiocarcinoma (CCA) in various ways. MASLD may have an increased risk of intrahepatic-CCA, whereas untreated patients with shorter diabetes durations were more likely to develop biliary tract cancer (BTC). More research is needed to understand how reproductive hormones cause BTC. BTC patients may be at increased intrinsic cardiovascular risk of neoplastic/non-neoplastic cardiac complications. Therefore, early detection/prevention of chronic liver disease, as well as intervention studies, will almost certainly be required to determine whether improvements in MetS, weight loss, and diabetes therapy can reduce CCA risk and progression. BTC overall incidence is globally increasing. CCA, including its subtypes, is a form of BTC. MetS, obesity, MASLD, and diabetes are all linked to CCA in interconnected ways. The link between obesity and CCA is less well-defined in Eastern countries as compared to Western. Although more research is needed to determine the relationship between MASLD and extrahepatic CCA (eCCA), MASLD may be a concurrent risk factor for intrahepatic CCA, particularly in populations with established or unidentified underlying liver disease. Interestingly, the risk of biliary tract cancer (BTC) seemed to be higher in patients with shorter diabetes durations who were not treated with insulin. Therefore, early detection and prevention of chronic liver disease, as well as additional intervention studies, will undoubtedly be required to determine whether improvements to MetS, weight loss, and diabetes therapy can reduce the risk and progression of BTC. However, further studies are needed to understand how reproductive hormones are involved in causing BTC and to develop consistent treatment for patients. Finally, it is critical to carefully assess the cardiological risk in BTC patients due to their increased intrinsic cardiovascular risk, putting them at risk for thrombotic complications, cardiovascular death, cardiac metastasis, and nonbacterial thrombotic endocarditis. This review aimed to provide an updated summary of the relation between the abovementioned cardio-metabolic conditions and BTC. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer of the upper digestive system is associated with poor survival due to difficulties in diagnosing the disease early, before it has spread around the body. Previous research has shown that the healthy bacteria within the body changes in response to medications, diet and infection. Some of these changes are associated with a greater risk of developing cancers of the oesophagus (gullet) and stomach. This occurs, at least in part, through inflammation. This process is the body's natural response to infection, injury and exposure to potentially harmful substances, which, if uncontrolled can lead to diseases including cancer. This review article aims to explain the ways in which this happens. By developing a deeper understanding of these processes, advances in early diagnosis of this disease can be made, which may lead to better survival. Introduction: The upper gastrointestinal microbiome is a dynamic entity that is involved in numerous processes including digestion, production of vitamins and protection against pathogens. Many external and intrinsic factors may cause changes in the proportions of bacteria within the microbial community, termed 'dysbiosis'. A number of these have been identified as risk factors for a range of diseases, including oesophago-gastric carcinoma. Materials and Methods: A narrative review was conducted to elucidate the current evidence on the role of the microbiome in promoting oesophago-gastric tumourigenesis. Significant causes of dysbiosis including age, medications and GORD were examined and key pro-inflammatory pathways implicated in tumourigenesis and their interaction with the microbiome were described. Results and Discussion: An association between microbial dysbiosis and development of oesophago-gastric cancer may be mediated via activation of pro-inflammatory pathways, the inflammasome and the innate immune system. Advances in sequencing technology allow microbial communities to be fingerprinted by sequencing the 16S rRNA gene, enabling a deeper understanding of the genera that may be implicated in driving tumourigenesis. Conclusions: Developing a greater understanding of the influence of the microbiota on oesophago-gastric tumourigenesis may enable advances to be made in the early detection of malignancy and in the development of novel systemic therapies, leading to improved rates of survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Salivary gland tumors (SGTs) are rare and complex, making them difficult to diagnose and treat. This work focuses on the role of exosomes, extracellular vesicles secreted by almost all cell types, in the development and progression of SGT. Exosomes are crucial in cell-to-cell communication and play significant roles in tumor biology, including modulating the tumor environment, aiding metastasis, and affecting immune responses. A better understanding of exosome biology can lead to their use as biomarkers for diagnosis and prognosis, as well as targets for treatment, potentially transforming SGT management and improving patient outcomes. Exosome-based liquid biopsies could offer non-invasive, real-time diagnostics and enhance patient care through precision medicine. This review explores the advancements in salivary exosome analysis, highlighting its potential for non-invasive cancer detection and the development of innovative diagnostic techniques. Backgroud: Salivary gland tumors (SGTs) are rare and diverse neoplasms, presenting significant challenges in diagnosis and management due to their rarity and complexity. Exosomes, lipid bilayer vesicles secreted by almost all cell types and present in all body fluids, have emerged as crucial intercellular communication agents. They play multifaceted roles in tumor biology, including modulating the tumor microenvironment, promoting metastasis, and influencing immune responses. Results: This review focuses on the role of exosomes in SGT, hypothesizing that novel diagnostic and therapeutic approaches can be developed by exploring the mechanisms through which exosomes influence tumor occurrence and progression. By understanding these mechanisms, we can leverage exosomes as diagnostic and prognostic biomarkers, and target them for therapeutic interventions. The exploration of exosome-mediated pathways contributing to tumor progression and metastasis could lead to more effective treatments, transforming the management of SGT and improving patient outcomes. Ongoing research aims to elucidate the specific cargo and signaling pathways involved in exosome-mediated tumorigenesis and to develop standardized techniques for exosome-based liquid biopsies in clinical settings. Conclusions: Exosome-based liquid biopsies have shown promise as non-invasive, real-time systemic profiling tools for tumor diagnostics and prognosis, offering significant potential for enhancing patient care through precision and personalized medicine. Methods like fluorescence, electrochemical, colorimetric, and surface plasmon resonance (SPR) biosensors, combined with artificial intelligence, improve exosome analysis, providing rapid, precise, and clinically valid cancer diagnostics for difficult-to-diagnose cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: This article examines the significance of β-chemokines, γ-chemokines, and δ-chemokines in acute myeloid leukemia (AML). It focuses on the effects of these chemotactic cytokines on both leukemic cells and non-leukemic cells within the tumor niche in the bone marrow. This article emphasizes the substantial impact of certain chemokines on tumorigenic processes in AML, highlighting the correlation between chemokine expression and patient prognosis. However, the mechanisms underlying this relationship remain poorly understood. The lack of comprehensive understanding of the role of chemokines in AML impedes the development of new anti-leukemic drugs targeting these chemokines and their receptors. Background/Objectives: Acute myeloid leukemia (AML) is a type of leukemia with a very poor prognosis. Consequently, this neoplasm is extensively researched to discover new therapeutic strategies. One area of investigation is the study of intracellular communication and the impact of the bone marrow microenvironment on AML cells, with chemokines being a key focus. The roles of β-chemokines, γ-chemokines, and δ-chemokines in AML processes have not yet been sufficiently characterized. Methods: This publication summarizes all available knowledge about these chemotactic cytokines in AML and myelodysplastic neoplasm (MDS) processes and presents potential therapeutic strategies to combat the disease. The significance of β-chemokines, γ-chemokines, and δ-chemokines is detailed, including CCL2 (MCP-1), CCL3 (MIP-1α), CCL5 (RANTES), CCL23, CCL28, and CX3CL1 (fractalkine). Additionally, the importance of atypical chemokine receptors in AML is discussed, specifically ACKR1, ACKR2, ACKR4, and CCRL2. Results/Conclusions: The focus is on the effects of these chemokines on AML cells, particularly their influence on proliferation and resistance to anti-leukemic drugs. Intercellular interactions with non-AML cells, such as mesenchymal stem cells (MSC), macrophages, and regulatory T cells (Treg), are also characterized. The clinical aspects of chemokines are thoroughly explained, including their effect on overall survival and the relationship between their blood levels and AML characteristics. [ABSTRACT FROM AUTHOR]

Epidemiological and observational studies suggest that vitamin D has potential for the chemoprevention of ovarian cancer. The anticancer effect of vitamin D in the fallopian tube epithelium (FTE), which is now thought to harbor the precursor cells for high grade ovarian cancer, is not known. The purpose of this study was to investigate whether vitamin D can inhibit carcinogenesis in the mogp-TAg fallopian tube (FT) ovarian cancer mouse model and examine underlying mechanisms. To test this hypothesis, 3 groups of 40 5-week-old female mogp-TAg mice were divided equally into two cohorts of 20 mice, treated with either vehicle (vitamin D solvent) or the active 1,25(OH)2D3 analogue EB1089, delivered via mini-pump or IP injection or cholecalciferol delivered in the feed. The FTs were characterized histologically and pathologically after 3 and 7 weeks of treatment. The effect of vitamin D on cultured human FTE cells was also examined. After 3 weeks, vitamin D, delivered as either cholecalciferol or EB1089 significantly inhibited FT carcinogenesis. After 7 weeks, cholecalciferol significantly reduced p53 signatures, serous tubal epithelial carcinoma, FT cancer, and plasma CA125 while increasing apoptosis in the FTE. EB1089 had no significant effect on FT carcinogenesis at 7 weeks. Cholecalciferol significantly reduced proliferation and increased apoptosis in vitro in p53-altered FTE cells. In conclusion, vitamin D inhibited FT carcinogenesis by clearing cells with p53 alterations. These data suggest that vitamin D has merit for the chemoprevention of fallopian tube/ovarian cancer. The optimal chemopreventive effect may be dependent on the route of vitamin D administration [ABSTRACT FROM AUTHOR]

Human Carbonic Anhydrases (hCA) are enzymes that contribute to cancer's development and progression. Isoforms IX and XII have been identified as potential anticancer targets, and, more specifically, hCA IX is overexpressed in hypoxic tumor cells, where it plays an important role in reprogramming the metabolism. With the aim to find new inhibitors towards IX and XII isoforms, the hybridization of the privileged scaffolds isatin, dihydrothiazole, and benzenesulfonamide was investigated in order to explore how it may affect the activity and selectivity of the hCA isoforms. In this respect, a series of isatin thiazolidinone hybrids have been designed and synthesized and their biological activity and selectivity on hCA I, hCA II, hCA IX, and hCA XII explored. The new compounds exhibited promising inhibitory activity results on isoforms IX and XII in the nanomolar range, which has highlighted the importance of substituents in the isatin ring and in position 3 and 5 of thiazolidinone. In particular, compound 5g was the most active toward hCA IX, while 5f was the most potent inhibitor of hCA XII within the series. When both potency and selectivity were considered, compound 5f appeared as one of the most promising. Additionally, our investigations were supported by molecular docking experiments, which have highlighted the putative binding poses of the most promising compound. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to determine the gene expression profiles associated with chemotherapeutic responses in conventional osteosarcomas (COS) within South Africa. We observed a significant downregulation in the ATP binding cassette subfamily C members (ABCC3 and ABCB1-p-glycoprotein), excision repair cross-complimenting group 1 (ERCC 1), replication factor C subunit 1 (RFC1), and tumour protein 53 (p53) genes in the COS tumours compared to the healthy donors. Furthermore, an upregulated ERCC1 gene expression level predicted a poor chemotherapeutic response. Additionally, the predictors of COS chemotherapeutic response comprised age, chondroblastic and osteoblastic histological subtypes, and ABCC3, ERCC1, and RFC1 gene expression. Background: We determined the predictive gene expression profiles associated with chemo-response in conventional osteosarcomas (COS) within South Africa. Materials and methods: In 28 patients, we performed an RNA extraction, cDNA synthesis, and quantitative analysis using the RT-PCR 2−∆∆CT method to determine the fold change in gene expression alongside GAPDH (housekeeping gene). Results: We observed a significant downregulation in the mRNA expression profiles of ABCB1-p-glycoprotein (p = 0.0007), ABCC3 (p = 0.002), ERCC1 (p = 0.007), p-53 (p = 0.007), and RFC1 (p = 0.003) in the COS patients compared to the healthy donors. Furthermore, ABCB1-p-glycoprotein (p = 0.008) and ABCC3 (p = 0.020) exhibited a significant downregulation in the COS tumour tissues when compared to the healthy donors. In our univariate logistic regression, the predictors of chemotherapeutic response comprised ERCC1 [restricted cubic spline (RCS) knot: OR −0.27; CI −0.504 to −0.032; p = 0.036]; osteoblastic subtype [OR −0.36; CI −0.652 to −0.092; p = 0.026); fibroblastic subtype [OR 0.91; CI 0.569 to 1.248; p < 0.001]; and mixed subtype [OR 0.53; CI 0.232 to 0.032; p = 0.032]. In our multivariable logistic regression, the significant predictors of chemotherapeutic response comprised age [RCS knot: OR −2.5; CI −3.616 to −1.378; p = 0.022]; ABCC3 [RCS knot: OR 0.67; CI 0.407 to 0.936, p = 0.016]; ERCC1 [RCS knot: OR 0.57; CI 0.235 to 0.901; p = 0.044]; RFC1 [RCS knot: OR −1.04; CI −1.592 to −0.487; p = 0.035]; chondroblastic subtype [OR −0.83; CI −1.106 to −0.520; p = 0.012]; and osteoblastic subtype [OR −1.28; CI −1.664 to −0.901; p = 0.007]. Conclusions: In this South African cohort, we observed the unique gene expression profiles of osteosarcoma tumourigenesis and chemotherapeutic responses. These may serve as prognostication and therapeutic targets. Larger-scale research is needed on the African continent. [ABSTRACT FROM AUTHOR]

Simple Summary: Currently, delivering nanoparticles to hard-to-reach tumor sites remains a challenge in nanomedicine. Mesenchymal stem cells are an innovative strategy for targeting tumors, and genetic engineering could enable them to release antitumor agents and/or nanomaterials at tumor sites. Therefore, combining radiosensitizing agents with mesenchymal stem cells represents a promising strategy in the fight against cancer. Still, evaluating whether nanoparticles can modulate mesenchymal stem cells' behavior is essential. This study assessed the impact of new Fe3O4@Au nanoparticles on human pulmonary mesenchymal stem cells to determine whether they can be used as carriers for radiosensitizer agents to cancer sites. This study focused on the markers related to cell death, redox and proinflammatory status, and tumorigenesis. Background/Objectives: Metallic nanoparticles (NPs) exhibit interesting radiosensitizing effects, and finding a way to accurately deliver them appears to be crucial. Due to their tumor tropism, mesenchymal stem cells (MSCs) represent a strategic approach. Therefore, we aimed to evaluate the impact of core–shell Fe3O4@Au NPs on the functionality of human pulmonary MSCs (HPMSCs). Methods/Results: The results showed that 100 µg/mL Fe3O4@Au NPs, accumulated in HPMSCs (revealed by Prussian blue staining), did not alter cell viability as assessed by cell counting, MTT, and LDH assays. However, caspase 9 and Bcl2 gene expression, evaluated by RT-qPCR, was regulated 72 h after exposure to the NPs. Moreover, the NPs also decreased proinflammatory cytokine/chemokine secretions, except for CXCL8 (ELISA). These modulations were associated with the downregulation of AMPK gene expression at 24 h. In contrast, the NPs did not modulate VEGF, PI3K, or PDGF gene expression. Nevertheless, a decrease in VEGF secretion was observed after 24 h of exposure to the NPs. Interestingly, the Fe3O4@Au NPs did not modulate Nrf2 gene expression, but they did regulate the expression of the genes encoding Nox4 and HMOX-1. Additionally, the NPs increased ROS production, suggesting a redox imbalance. Conclusions: Finally, the Fe3O4@Au NPs did not affect the HPMSCs' viability or proangiogenic/tumorigenic markers. These findings are encouraging for investigating the effects of Fe3O4@Au NPs delivered by HPMSCs to tumor sites in combination with radiation. [ABSTRACT FROM AUTHOR]

Simple Summary: We provide a historical perspective on the current concepts of minimal residual disease (MRD) and how it evolves from minimal residual disease to measurable residual disease. We aim to highlight the fundamental biology behind MRD—the overlap between leukemia stem cells and MRD, and the role of the bone marrow microenvironment in the persistence of MRD. We describe how our success in measuring and subsequently eliminating residual disease in acute promyelocytic leukemia will pave the way towards progress in other acute leukemias. Introduction: Advances in molecular biology, polymerase chain reaction (PCR), and next-generation sequencing (NGS) have transformed the concept of minimal residual disease (MRD) from a philosophical idea into a measurable reality. Current Treatment Paradigms and Lessons Learned from APL: Acute promyelocytic leukemia (APL) leads the way in this transformation, initially using PCR to detect MRD in patients in remission, and more recently, aiming to eliminate it entirely with modern treatment strategies. Along the way, we have gained valuable insights that, when applied to other forms of acute leukemia, hold the potential to significantly improve the outcomes of these challenging diseases. Does the BM Microenvironment Play a Role in MRD?: In this review, we explore the current use of MRD in the management of acute leukemia and delve into the biological processes that contribute to MRD persistence, including its overlap with leukemia stem cells and the role of the bone marrow microenvironment. [ABSTRACT FROM AUTHOR]

Simple Summary: MicroRNAs (miRNAs) play a significant role in the initiation and progression of colorectal cancer and are extensively well-studied in this context. However, the interplay between miRNAs and RNA-binding proteins, especially HuR, is yet to be fully understood. In this review, we summarize the regulatory role of the HuR-miRNA axis in colorectal cancer, highlighting its importance for an improved diagnostic or prognostic approach. Colorectal cancer (CRC) remains a significant global health burden with high incidence and mortality. MicroRNAs (miRNAs) are small non-protein coding transcripts, conserved throughout evolution, with an important role in CRC tumorigenesis, and are either upregulated or downregulated in various cancers. RNA-binding proteins (RBPs) are known as essential regulators of miRNA activity. Human antigen R (HuR) is a prominent RBP known to drive tumorigenesis with a pivotal role in CRC. In this review, we discuss the regulatory role of the HuR/miRNA axis in CRC. Interestingly, miRNAs can directly target HuR, altering its expression and activity. However, HuR can also stabilize or degrade miRNAs, forming complex feedback loops that either activate or block CRC-associated signaling pathways. Dysregulation of the HuR/miRNA axis contributes to CRC initiation and progression. Additionally, HuR-miRNA regulation by other small non-coding RNAs, circular RNA (circRNAs), or long-non-coding RNAs (lncRNAs) is also explored here. Understanding this HuR-miRNA interplay could reveal novel biomarkers with better diagnostic or prognostic accuracy. [ABSTRACT FROM AUTHOR]

Simple Summary: End-stage renal disease (ESRD) is a life-threatening condition that necessitates renal replacement therapies such as dialysis. ESRD is believed to increase cancer risk and cancer mortality rate; however, data on cancer risk and cancer-specific mortality in patients with ESRD present multiple statistical issues, including sampling errors, bias, and confounding factors, falsely depicting high cancer incidence. Only renal cell and urothelial cancers are driven by ESRD. However, cancer-specific mortality is generally lower in patients with ESRD than in the general population, which corresponds to the fact that cancers arising from ESRD are generally less aggressive and have low metastatic potential. ESRD damages not only normal but also malignant cells in multiple stages of cancer development. This review highlights the potential anticancer effects of ESRD, proposing a reconsideration of the hypothesis that ESRD promotes cancer development and progression. The prevalence of end-stage renal disease is increasing worldwide. Malignancies accompanying end-stage renal disease are detected in approximately 120 individuals per 10,000 person-years. Most studies have suggested that end-stage renal disease causes carcinogenesis and promotes tumor development; however, this theory remains questionable. Contrary to the theory that end-stage renal disease is predominantly carcinogenic, recent findings have suggested that after controlling for biases and sampling errors, the overall cancer risk in patients with end-stage renal disease might be lower than that in the general population, except for renal and urothelial cancer risks. Additionally, mortality rates associated with most cancers are lower in patients with end-stage renal disease than in the general population. Several biological mechanisms have been proposed to explain the anticancer effects of end-stage renal disease, including premature aging and senescence, enhanced cancer immunity, uremic tumoricidal effects, hormonal and metabolic changes, and dialysis therapy-related factors. Despite common beliefs that end-stage renal disease exacerbates cancer risk, emerging evidence suggests potential tumor-suppressive effects. This review highlights the potential anticancer effects of end-stage renal disease, proposing reconsideration of the hypothesis that end-stage renal disease promotes cancer development and progression. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that the passenger strands microRNAs (miRNAs) derived from pre-miRNAs are closely involved in cancer pathogenesis. Analysis of our miRNA expression signature of lung adenocarcinoma (LUAD) and The Cancer Genome Atlas (TCGA) data revealed that miR-144-5p (the passenger strand derived from pre-miR-144) was significantly downregulated in LUAD tissues. The aim of this study was to identify therapeutic target molecules controlled by miR-144-5p in LUAD cells. Ectopic expression assays demonstrated that miR-144-5p attenuated LUAD cell aggressiveness, e.g., inhibited cell proliferation, migration and invasion abilities, and induced cell cycle arrest and apoptotic cells. A total of 18 genes were identified as putative cancer-promoting genes controlled by miR-144-5p in LUAD cells based on our in silico analysis. We focused on a family with sequence similarity 111 member B (FAM111B) and investigated its cancer-promoting functions in LUAD cells. Luciferase reporter assay showed that expression of FAM111B was directly regulated by miR-144-5p in LUAD cells. FAM111B knockdown assays showed that LUAD cells significantly suppressed malignant phenotypes, e.g., inhibited cell proliferation, migration and invasion abilities, and induced cell cycle arrest and apoptotic cells. Furthermore, we investigated the FAM111B-mediated molecular networks in LUAD cells. Identifying target genes regulated by passenger strands of miRNAs may aid in the discovery of diagnostic markers and therapeutic targets for LUAD. [ABSTRACT FROM AUTHOR]

(1) Background: Few studies focus on the development of obesity as a chronic disease as opposed to an acute condition. The "general purpose" C3H/HeJ (C3H) mouse strain is an alternative model for obesity development with regards to sex disparities and non-predisposed populations over time. (2) Methods: In this study, 64 female and 64 male C3H mice were separated into two groups (n = 32) and maintained on a control or high-fat diet (HFD) for up to 18 months. At 6-month intervals, a cross-sectional cohort (n = ~8) was censored for evaluation. The mice were monitored for change in total, lean and fat mass, survivability, and tumor incidence. (3) Results: Both sexes in the C3H mouse strain developed diet-induced obesity (DIO). An increase in total mass consistent with a HF diet was observed in both female and male C3H mice. Survivorship at 18 months was the highest in the HF-diet-fed males (~62%) and lowest in the males fed the control diet (~19%). Females showed survivability at ~40%, regardless of diet. Cancer development increased more notably in the males with the HF diet and showed sex bias for liver cancer (males) and ovarian cancer (females) incidence with age. (4) Conclusions: This study establishes a baseline for future use of C3H mice as a strong model for studying obesity as a chronic disease, in both sexes, and as long-term model for age-related diet-induced obesity and cancer development. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common type of cancer globally and presents an escalating problem and a huge burden on societies. Several strategies are implemented in clinics to treat patients and prevent disease incidence. Efforts to understand the underlying causes of disease emergence are pivotal, and the latest examination of human transcriptomic studies showed the involvement of the noncoding RNA regulatory molecules in influencing both pathological and physiological conditions. Several molecular mechanisms are involved in the process and collaborate to develop tumor plasticity and drug resistance. In this review, we highlight for the first time the interplay between long noncoding RNAs and Aurora kinases in breast cancer and review the latest advances in the field in an attempt to pave the way for a better understanding of the course of the disease and to delineate the targets for treatment strategies in the clinic. [ABSTRACT FROM AUTHOR]

Despite significant advancements in the field of oncology, cancers still pose one of the greatest challenges of modern healthcare. Given the cytoskeleton's pivotal role in regulating mechanisms critical to cancer development, further studies of the cytoskeletal elements could yield new practical applications. Septins represent a group of relatively well-conserved GTP-binding proteins that constitute the fourth component of the cytoskeleton. Septin 9 (SEPT9) has been linked to a diverse spectrum of malignancies and appears to be the most notable septin member in that category. SEPT9 constitutes a biomarker of colorectal cancer (CRC) and has been positively correlated with a high clinical stage in breast cancer, cervical cancer, and head and neck squamous cell carcinoma. SEPT9_i1 represents the most extensively studied isoform of SEPT9, which substantially contributes to carcinogenesis, metastasis, and treatment resistance. Nevertheless, the mechanistic basis of SEPT9_i1 oncogenicity remains to be fully elucidated. In this review, we highlight SEPT9's and SEPT9_i1's structures and interactions with Hypoxia Inducible Factor α (HIF-1 α) and C-Jun N-Terminal Kinase (JNK), as well as discuss SEPT9_i1's contribution to aneuploidy, cell invasiveness, and taxane resistance—key phenomena in the progression of malignancies. Finally, we emphasize forchlorfenuron and other septin inhibitors as potential chemotherapeutics and migrastatics. [ABSTRACT FROM AUTHOR]

Background/Objectives: The relationship between sarcoidosis and the occurrence of neoplasia deserves to be investigated, but this relation has been observed in different and heterogeneous populations, leading to conflicting data. To clarify the causal relationship between these two diseases, different risk factors (e.g., smoking), concurrent comorbidities, corticosteroid therapy, and metastasis development—as an expression of cancer aggressiveness—were investigated. Methods: In a retrospective study on 287 sarcoidosis outpatients at the Pneumological Department of the Gemelli Foundation (Rome, Italy) between 2000 and 2024, the diagnosis of cancer was recorded in 36 subjects (12.5%). Results: The reciprocal timeline of the diseases showed three different scenarios: (1) cancer preceding sarcoidosis or sarcoid-like reactions (63.8%); (2) cancer arising after sarcoidosis diagnosis (8.3%); and (3) sarcoidosis accompanying the onset of malignancy (27.8%). Only two subjects with sarcoidosis and cancer showed metastasis, and one of them was affected by lymphoma. Conclusions: These data suggest that granulomatous inflammation due to sarcoidosis may assume an ambivalent role as a "double-edged sword", according to the M1/M2 macrophage polarization model: it represents a protective shield, preventing the formation of metastasis through the induction of immune surveillance against cancer while, on the other hand, it can be a risk factor for carcinogenesis due to the persistence of a chronic active inflammatory status. Low-dose steroid treatment was administered in only 31.6% of the cancer–sarcoidosis subjects for less than six months to control inflammation activity, with no promotive effect on carcinogenesis observed. [ABSTRACT FROM AUTHOR]

Simple Summary: Wilms tumor is the most common pediatric primary renal malignancy globally but exhibits significant variations in epidemiological, clinical, and molecular aspects among different populations. Wilms tumor has been shown to occur at lower incidences, younger ages, and earlier stages of disease with higher incidences of favorable histology among Asians compared to Caucasians. Despite a worldwide convergence between the two main management approaches, it is not known if these are generalizable to all ethnic populations. This paper summarizes the current literature on the inter-ethnic variations in the clinical, pathological, and molecular characteristics of Wilms tumor. Wilms tumor is the commonest primary renal malignancy in children and demonstrates substantial inter-ethnic variation in clinical, pathological, and molecular characteristics. Wilms tumor occurs at a lower incidence and at a younger age in Asians compared to Caucasians and Africans. Asians also present at an earlier stage of disease, with a higher incidence of favorable histology tumors and a lower incidence of perilobar nephrogenic rests compared to Caucasians, while African children present with more advanced disease. Studies have implicated population differences in the incidence of WT1 mutations, loss of imprinting of the IGF2 locus, and loss of heterozygosity of 1p/16q, or 1q gain as possible bases for epidemiological differences in the disease profile of Wilms tumors in various ethnic groups. Yet, evidence to support these associations is confounded by differences in treatment protocols and inequalities in the availability of treatment resources and remains limited by the quality of population-based data, especially in resource-limited settings. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores whether Escherichia coli carrying the polyketide synthetase (pks) gene cluster in colorectal cancer (CRC) liver metastasis tissues influence immune responses and cancer recurrence patterns. Analyzing tissues from 239 patients, we found that pks+ E. coli was present in 66.7% of liver metastasis cases. Higher levels of pks+ E. coli were associated with lower levels of the serum C-reactive protein, fewer densities of CD4+ cells and CD163+ cells in the tumor microenvironment, and a reduction in the number of organs affected by recurrent metastasis. These findings suggest that pks+ E. coli may influence both systemic and local immune responses, potentially reducing the diversity of affected metastatic organs. Colibactin, a genotoxin produced by Escherichia coli strains harboring the polyketide synthetase (pks) gene cluster, causes DNA damage and somatic mutations. pks+ E. coli is enriched in primary colorectal cancer (CRC) and is associated with clonal driver mutations, but its role in CRC liver metastasis is unclear. We assessed the association of pks+ E. coli in CRC liver metastasis tissues with systemic and local immune responses and the number of organs involved in recurrence using specimens and clinicopathological data from 239 patients with CRC liver metastasis who underwent metastasectomy. The levels of pks+ E. coli in fresh-frozen specimens were quantified as "very low" (<50th percentile), "low" (50th to 75th percentiles), and "high" (>75th percentile) using a digital PCR. Immunohistochemical analysis of tumor-infiltrating immune cells was performed using tissue microarrays. Systemic inflammation was evaluated using serum C-reactive protein (CRP) levels. pks+ E. coli was detected in 66.7% (157 of 239) liver metastasis tissues. Higher levels of pks+E. coli were associated with decreased serum CRP levels and reduced densities of CD4+ cells and CD163+ cells in the tumor-immune microenvironment. The "high" pks+ E. coli group had fewer metastatic organs involved than the "very low" pks+ E. coli group (mean number of organs: 1.00 vs. 1.23). These findings suggest that pks+ E. coli play a modulating role in CRC metastasis. [ABSTRACT FROM AUTHOR]

Simple Summary: Racial healthcare disparities, driven by adverse living conditions, environmental factors, and systemic biases, significantly affect Black Americans, and they are associated with increased oxidative stress, inflammation, and, in turn, chronic diseases like cardiovascular disease and cancer. Addressing these disparities requires comprehensive systemic reforms alongside additional strategies such as increased exercise, stress reduction, and anti-inflammatory diets. This review highlights the relevant literature and aims to encourage further research on this important topic. The impact of racial healthcare disparities has been well documented. Adverse social determinants of health, such as poverty, inadequate housing, and limited access to healthcare, are intricately linked to these disparities and negative health outcomes, highlighting the profound impact that social and economic factors have on individuals' overall well-being. Recent evidence underscores the role of residential location on individual health outcomes. Despite the importance of a healthy lifestyle, regular physical activity, balanced nutrition, and stress management for favorable health outcomes, individuals living in socioeconomically disadvantaged areas may face obstacles in achieving these practices. Adverse living conditions, environmental factors, and systemic biases against Black Americans perpetuate allostatic load. This, compounded by decreased physical activity and limited healthy food options, may contribute to increased oxidative stress and inflammation, fundamental drivers of morbidities such as cardiovascular disease and cancer. Herein, we perform a narrative review of associations between healthcare disparities, chronic stress, allostatic load, inflammation, and cancer in Black Americans, and we discuss potential mechanisms and solutions. Additional research is warranted in the very important area of cancer disparities. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma is the most common brain tumour, with a poor prognosis of about 15 months despite intensive treatment. Many trials have tested new drugs targeting specific genes, but none have succeeded, and treatments have not changed since 2005. This review explores why clinical trials with these drugs failed. It highlights the potential of combining different drugs to overcome resistance and suggests ways to improve future trials. The goal is to understand treatment failures and find new drug combinations to improve survival for GBM patients. Glioblastoma (GBM) is the most prevalent central nervous system tumour (CNS). Patients with GBM have a dismal prognosis of 15 months, despite an intensive treatment schedule consisting of surgery, chemoradiation and concurrent chemotherapy. In the last decades, many trials have been performed investigating small molecule inhibitors, which target specific genes involved in tumorigenesis. So far, these trials have been unsuccessful, and standard of care for GBM patients has remained the same since 2005. This review gives an overview of trials investigating small molecule inhibitors on their own, combined with chemotherapy or other small molecule inhibitors. We discuss possible resistance mechanisms in GBM, focussing on intra- and intertumoral heterogeneity, bypass mechanisms and the influence of the tumour microenvironment. Moreover, we emphasise how combining inhibitors can help overcome these resistance mechanisms. We also address strategies for improving trial outcomes through modifications to their design. In summary, this review aims to elucidate different resistance mechanisms against small molecule inhibitors, highlighting their significance in the search for novel therapeutic combinations to improve the overall survival of GBM patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Uveal melanoma (UM) is the most common primary intraocular tumor in adults, with a high incidence of liver metastasis causing poor survival. However, the mechanisms underlying this liver tropism remain poorly understood. Our study focused on the roles of UM exosomes along the metastatic process. A comparison of protein cargos between exosomes derived from the primary UM tumor and metastasis reveals a prominent function of exosomes derived from parental cells, favoring the detachment of cells from the primary site. We also found that UM-derived exosomes played a significant role in the activation and transdifferentiation of human hepatic stellate cells (HHSCs), which contribute to the formation of a pre-metastatic niche in the liver, promote interaction with tumor cells, and ultimately might enhance the metastatic potential. UM is an aggressive intraocular tumor characterized by high plasticity and a propensity to metastasize in the liver. However, the underlying mechanisms governing liver tropism remain poorly understood. Given the emerging significance of exosomes, we sought to investigate the contribution of UM-derived exosomes to specific steps of the metastatic process. Firstly, we isolated exosomes from UM cells sharing a common genetic background and different metastatic properties. A comparison of protein cargo reveals an overrepresentation of proteins related to cytoskeleton remodeling and actin filament-based movement in exosomes derived from the parental cells that may favor the detachment of cells from the primary site. Secondly, we assessed the role of macrophages in reprogramming the HHSCs by exosomes. The activation of HHSCs triggered a pro-inflammatory and pro-fibrotic environment through cytokine production, upregulation of extracellular matrix molecules, and the activation of signaling pathways. Finally, we found that activated HHSCs promote increased adhesion and migration of UM cells. Our findings shed light on the pivotal role of exosomes in pre-metastatic niche construction in the liver. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICIs) are cancer immunotherapeutics that reinvigorate immune cells' ability to attack tumor cells. Despite remarkable results in some patients, ICIs do not demonstrate the same efficacy across all individuals. In this study, we present the first side-by-side comparison of an agent-based model (ABM) with an ordinary differential equation (ODE) model for ICIs targeting the PD-1/PD-L1 immune checkpoint. We consider tumor cells of high and low antigenicity and two distinct immune-cell kill mechanisms. Using key parameters calibrated from mouse bladder cancer studies, we simulate virtual tumors using both models. Our research identifies crucial tumor-immune characteristics that influence the efficacy of ICIs. By exploring the unique spatial insights provided by the ABM, we underscore the importance of considering the spatial complexity of the tumor microenvironment in mathematical models of ICIs, potentially paving the way for more effective cancer treatments. Since the introduction of the first immune checkpoint inhibitor (ICI), immunotherapy has changed the landscape of molecular therapeutics for cancers. However, ICIs do not work equally well on all cancers and for all patients. There has been a growing interest in using mathematical and computational models to optimize clinical responses. Ordinary differential equations (ODEs) have been widely used for mechanistic modeling in immuno-oncology and immunotherapy. They allow rapid simulations of temporal changes in the cellular and molecular populations involved. Nonetheless, ODEs cannot describe the spatial structure in the tumor microenvironment or quantify the influence of spatially-dependent characteristics of tumor-immune dynamics. For these reasons, agent-based models (ABMs) have gained popularity because they can model more detailed phenotypic and spatial heterogeneity that better reflect the complexity seen in vivo. In the context of anti-PD-1 ICIs, we compare treatment outcomes simulated from an ODE model and an ABM to show the importance of including spatial components in computational models of cancer immunotherapy. We consider tumor cells of high and low antigenicity and two distinct cytotoxic T lymphocyte (CTL) killing mechanisms. The preferred mechanism differs based on the antigenicity of tumor cells. Our ABM reveals varied phenotypic shifts within the tumor and spatial organization of tumor and CTLs despite similarities in key immune parameters, initial simulation conditions, and early temporal trajectories of the cell populations. [ABSTRACT FROM AUTHOR]

Simple Summary: Human cells are typically diploid, that is, they contain two sets of chromosomes. Some cells, however, contain three or more sets of chromosomes and are called polyploid. In the early 2000s, Kirsten Walen and Rengaswami Rajaraman and his associates independently reported that polyploid human cells are capable of undergoing asymmetric division via nuclear budding and bursting (amitosis), giving rise to daughter cells that proliferate rapidly and can contribute to tumorigenesis (transformation of normal cells to a neoplastic state). This commentary provides an update on these intriguing discoveries. Cell division is crucial for the survival of living organisms. Human cells undergo three types of cell division: mitosis, meiosis, and amitosis. The former two types occur in somatic cells and germ cells, respectively. Amitosis involves nuclear budding and occurs in cells that exhibit abnormal nuclear morphology (e.g., polyploidy) with increased cell size. In the early 2000s, Kirsten Walen and Rengaswami Rajaraman and his associates independently reported that polyploid human cells are capable of producing progeny via amitotic cell division, and that a subset of emerging daughter cells proliferate rapidly, exhibit stem cell-like properties, and can contribute to tumorigenesis. Polyploid cells that arise in solid tumors/tumor-derived cell lines are referred to as polyploid giant cancer cells (PGCCs) and are known to contribute to therapy resistance and disease recurrence following anticancer treatment. This commentary provides an update on some of these intriguing discoveries as a tribute to Drs. Walen and Rajaraman. [ABSTRACT FROM AUTHOR]

Simple Summary: Spatial transcriptomics is a technique of measuring gene expression with spatial resolution on a tissue slide, which is especially useful in cancer research. This scoping study reviews 41 articles published by the end of 2023 to examine current trends for employed methods, applications, and data analysis approaches for spatial transcriptomics, identifying challenges and practical uses of this technique in studying cancer. The research shows that cancer is a major focus in spatial transcriptomics studies, with certain tools and methods being particularly popular among scientists. However, many studies do not fully explain their data processing methods, making it hard to reproduce their results. Emphasis on transparent sharing of analysis scripts and tailored single-cell analysis methods for ST is recommended to enhance study reproducibility and reliability in the domain. This work may stand as a spatial transcriptomics developmental snapshot and reference to contemporary neoplasm biology research conducted through this technique. Spatial transcriptomics (ST) examines gene expression within its spatial context on tissue, linking morphology and function. Advances in ST resolution and throughput have led to an increase in scientific interest, notably in cancer research. This scoping study reviews the challenges and practical applications of ST, summarizing current methods, trends, and data analysis techniques for ST in neoplasm research. We analyzed 41 articles published by the end of 2023 alongside public data repositories. The findings indicate cancer biology is an important focus of ST research, with a rising number of studies each year. Visium (10x Genomics, Pleasanton, CA, USA) is the leading ST platform, and SCTransform from Seurat R library is the preferred method for data normalization and integration. Many studies incorporate additional data types like single-cell sequencing and immunohistochemistry. Common ST applications include discovering the composition and function of tumor tissues in the context of their heterogeneity, characterizing the tumor microenvironment, or identifying interactions between cells, including spatial patterns of expression and co-occurrence. However, nearly half of the studies lacked comprehensive data processing protocols, hindering their reproducibility. By recommending greater transparency in sharing analysis methods and adapting single-cell analysis techniques with caution, this review aims to improve the reproducibility and reliability of future studies in cancer research. [ABSTRACT FROM AUTHOR]

Simple Summary: The increasing production of plastics and the failure to properly manage their post use represent the primary sources of environmental and human contamination caused by plastic degradation products, namely micro- and nano-plastics (MNPLs). Accumulating evidence supports the intestinal toxicity of ingested MNPLs, and their possible role as a driver for the increased incidence of colorectal cancer (CRC) has also been proposed. Moreover, colonic mucus layer disruption may further facilitate MNPL passage into the bloodstream, thus promoting the toxic effects of MNPLs on different organ systems. We herein discuss the pathophysiological mechanisms impaired by MNPL oral exposure in healthy conditions and individuals with compromised intestinal barrier function, including inflammatory bowel disease (IBD) and CRC patients, considered high-risk populations, by highlighting the potential contribution of MNPL-induced platelet activation. Micro- and nano-plastics (MNPLs) can move along the food chain to higher-level organisms including humans. Three significant routes for MNPLs have been reported: ingestion, inhalation, and dermal contact. Accumulating evidence supports the intestinal toxicity of ingested MNPLs and their role as drivers for increased incidence of colorectal cancer (CRC) in high-risk populations such as inflammatory bowel disease (IBD) patients. However, the mechanisms are largely unknown. In this review, by using the leading scientific publication databases (Web of Science, Google Scholar, Scopus, PubMed, and ScienceDirect), we explored the possible effects and related mechanisms of MNPL exposure on the gut epithelium in healthy conditions and IBD patients. The summarized evidence supports the idea that oral MNPL exposure may contribute to intestinal epithelial damage, thus promoting and sustaining the chronic development of intestinal inflammation, mainly in high-risk populations such as IBD patients. Colonic mucus layer disruption may further facilitate MNPL passage into the bloodstream, thus contributing to the toxic effects of MNPLs on different organ systems and platelet activation, which may, in turn, contribute to the chronic development of inflammation and CRC development. Further exploration of this threat to human health is warranted to reduce potential adverse effects and CRC risk. [ABSTRACT FROM AUTHOR]

Simple Summary: Azacytidine and donor lymphocyte infusions were combined effectively in a single-center high-risk patient cohort (n = 29) for post-transplant relapse of acute myeloid leukemia and myelodysplastic syndrome. Bone marrow Wilms tumor gene 1 (WT1) expression was measured at time of transplant and post-transplant relapse. By using the Cox proportional hazards model, cut-off values for WT1 at both time points were obtained. The disease risk index incorporating initial cytogenetics and the disease stage at transplant as well as WT1 expression was significantly associated with overall survival, indicating that WT1 may represent a minimal residual disease marker in this context of cell therapy response evaluation, especially in high-risk patients currently considered to be in complete remission. Cut-off values for bone marrow WT1 expression for the two decisive treatment time points were proposed. Introduction: Post-transplant relapse of acute myeloid leukemia and myelodysplastic syndrome faces restricted effective salvage regimens. We retrospectively analyzed the use of Azacitidine–donor lymphocyte infusion (AZA/DLI) in this setting. Furthermore, data on bone marrow Wilms tumor gene 1 (WT1) expression were collected. Methods: A Cox proportional hazards model, an outcome-oriented approach for the lowest smoothed plot of the martingale residuals, was performed for the cut-point determination of the respective WT1 expression levels. Finally, a Cox proportional hazards model investigated the association of overall survival (OS) with predictors. Results: An overall response of 41.4% with a median duration of 11.9 months for stable disease and 19.5 months for complete response (CR) patients was achieved. The disease risk index (DRI) high-/very high-risk patients had a shorter OS of 4.4 months than intermediate-risk patients, with 14.5 months, p = 0.007. At transplant, WT1-overexpressing patients (>150 copies) had a shorter median OS of 5.3 months than low-WT1-expressing ones, with 13.5 months, p = 0.024. Furthermore, patients with ≤1000 WT1 copies at relapse had a significantly longer OS with 15.3 months than patients overexpressing WT1, with 4.4 months, p = 0.0002. Conclusions: DRI and WT1 expression associate significantly with OS after AZA/DLI. Hence, WT1 may represent an MRD marker, especially in CR patients at high risk. [ABSTRACT FROM AUTHOR]

The NR2F family, including NR2F1, NR2F2, and NR2F6, belongs to the nuclear receptor superfamily. NR2F family members function as transcription factors and play essential roles in the development of multiple organs or tissues in mammals, including the central nervous system, veins and arteries, kidneys, uterus, and vasculature. In the central nervous system, NR2F1/2 coordinate with each other to regulate the development of specific brain subregions or cell types. In addition, NR2F family members are associated with various cancers, such as prostate cancer, breast cancer, and esophageal cancer. Nonetheless, the roles of the NR2F family in the development and diseases of the lung have not been systematically summarized. In this review, we mainly focus on the lung, including recent findings regarding the roles of the NR2F family in development, physiological function, and cancer. [ABSTRACT FROM AUTHOR]

(1) Background: Oral cavity cancer represents the most common site of origin of head and neck mucosal malignancies. A few limited studies have suggested that chronic irritation, particularly in non-healing ulcers, and fibrotic tissue from poor dentition or ill-fitting dentures had a role in developing mouth cancer. This scoping review aims to evaluate the existing evidence concerning Oral Cavicty Cancer (OCC) in non-smokers/non-drinkers and the relationship with dental trauma. (2) Methods: A scoping review of the PubMed, Embase, and Web of Science databases was completed in adherence with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews checklist. (3) Results: Of the 33 articles that met inclusion, in 6 of them authors discussed the role of topography in dental trauma, in 11 articles authors discussed the carcinogenesis mechanism involved in chronic mucosal trauma, in 17 articles data on ill-fitting dentures was included, 4 studies dealt with the effect of broken/sharp teeth on mucosal damage, and in 7 studies the role of oral hygiene was covered. Less frequently discussed topics included gender, risk of neck nodes, and the role of potentially malignant oral disorders. (4) Conclusions: The available literature suggests a potential connection between chronic dental trauma and the development of OCC. Studies have highlighted factors such as denture use and ill-fitting dental appliances as contributors to an increased risk of oral cancer. Interestingly, we still miss data to support the hypothesis that women, particularly those without toxic habits like smoking or alcohol consumption, appear to be disproportionately affected by oral cancer related to chronic dental trauma. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs), members of the nanomaterial family, are increasingly being used in consumer products and extensively studied for various biomedical applications. Due to their benign elemental composition, large surface area, and chemical and biological activities, CNTs demonstrate great potential in cancer therapy, including drug delivery, imaging analysis, photothermal therapy, photodynamic therapy, and radiotherapy. However, there is still a major knowledge gap when it comes to transitioning from research to clinical applications. One of the important issues is that the biological toxicity of CNTs, especially in terms of carcinogenesis, and the underlying mechanisms are not fully understood. Therefore, a thorough evaluation of toxicity and the underlying mechanisms of carcinogenesis is essential to enable the wide application of CNTs. In this review, we summarize the recent progress of CNTs as multifunctional therapeutics in cancer therapy. Furthermore, a detailed discussion is provided on the carcinogenesis and potential mechanisms of CNTs. Finally, the review ends with further challenges and prospects for CNTs with the expectation of facilitating their broader utilization. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that physiologically normal skin harbors pervasive mutant clones with cancer drivers. Normal skin has the highest burden of somatic mutations due to persistent ultraviolet exposure throughout life. The mutation burden exponentially increases with age and is further modified by skin site, sun-damage history, and skin phototype. Driver gene profiles in normal skin are similar to those in cutaneous squamous cell carcinoma where NOTCH family, FAT family, and TP53 are consistently reported, while other reported profiles include PPM1D, KMT2D, ASXL1, and RBM10. Normal skin seldom harbors canonical hotspot mutations with therapeutic relevance. The pathologic role of mutant clones with cancer drivers in normal skin is classically considered precursors for skin cancer; however, recent evidence also suggests their putative cancer-protective role. Copy number alterations and other structural variants are rare in normal skin with loss in 9q region encompassing NOTCH1 being the most common. Study methodologies should be carefully designed to obtain an adequate number of cells for sequencing, and a comparable number of cells and read depth across samples. In conclusion, this review provides mutational landscapes of normal skin and discusses their potential implications in the development of skin cancer, highlighting the role of driver genes in early malignant progression. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective observational study recruited 380 patients, 115 with lung cancer and 265 in the control group. Both the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR) were significantly higher in cancer patients than in the control group. The correlation of PLR with the probability of lung cancer differs between men and women. CRP values did not differ according to histological types of lung cancer (p = 0.242) and were not associated with the presence of mutations in EGFR (p = 0.679). CRP values were significantly lower in NSCLC patients with PD-L1 mutations than in those without PD-L1 mutations (22.7 [IQR: 10.4;40.3] vs. 76.7 [IQR: 32.6;140] mg/L, p = 0). Background and objective: Analysis of inflammatory biomarkers, along with the neutrophil/lymphocyte ratio (NLR) or platelet/lymphocyte ratio (PLR), supports the connection between inflammation and carcinogenesis. Methods: We conducted a retrospective observational study at the Clinical County Hospital Mureș involving patients with lung cancer. The parameters analyzed included histopathological type (NSCLC: squamous cell carcinoma or adenocarcinoma; SCLC), molecular mutations (EGFR, ALK, PD-L1), parameters from the complete blood count, inflammatory parameters, and associated comorbidities. Results: A total of 380 patients were included: 115 patients in the cancer group and 265 patients in the control group. Among patients in the lung cancer group, 88 were diagnosed with NSCLC (44 adenocarcinomas, 44 squamous cell carcinomas) and 27 with SCLC. Both NLR and PLR were significantly higher in cancer patients than in the control group (5.30 versus 2.60, p < 0.001; 217 versus 136, p < 0.001, respectively). NLR and PLR differ between men and women (p = 0.005 and p = 0.056, respectively). C-reactive protein was not correlated with either NLR (p-value: 0.0669) or PLR (p-value: 0.6733) in lung cancer patients. Conclusions: The NLR and PLR values may serve as new predictive biomarkers for the diagnosis of disease in patients with lung cancer, especially those with NSCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous squamous cell carcinoma (cSCC) is a complex disease arising from an interplay of UV-induced DNA damage, genetic mutations, and alterations in the tumor microenvironment. While most cSCC cases can be treated with surgery, metastatic and locally advanced forms have a significantly worse prognosis and limited treatment options. The high mutational burden in cSCC makes it challenging to identify true driver alterations. Beyond genetics, the tumor microenvironment and its interaction with the immune system play a critical role in cSCC progression, evidenced by differences observed between immunocompromised and immunocompetent patients. In recent years, new therapeutic approaches have emerged, including immunotherapy and EGFR inhibitors, which have shown efficacy in treating advanced cSCC. Understanding the underlying mechanisms driving cSCC is crucial for developing novel and more effective therapies. This review aims to provide a comprehensive overview of the mutational landscape and microenvironmental factors in cSCC. Cutaneous squamous cell carcinoma (cSCC) manifests through the complex interactions of UV-induced DNA damage, genetic mutations, and alterations in the tumor microenvironment. A high mutational burden is present in cSCC, as well as both cSCC precursors and normal skin, making driver genes difficult to differentiate. Despite this, several key driver genes have been identified, including TP53, the NOTCH family, CDKN2A, PIK3CA, and EGFR. In addition to mutations, the tumor microenvironment and the manipulation and evasion of the immune system play a critical role in cSCC progression. Novel therapeutic approaches, such as immunotherapy and EGFR inhibitors, have been used to target these dysregulations, and have shown promise in treating advanced cSCC cases, emphasizing the need for targeted interventions considering both genetic and microenvironmental factors for improved patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Resistance to standard therapies represents a major challenge in melanoma treatment. This is mainly related to the high heterogeneity of this malignancy due to the presence of different types of cells in the tumor mass. Cancer stem cells (CSCs) are a small subset of cells endowed with self-renewal and tumorigenic capacity and the ability to escape anticancer therapies. Melanoma CSCs can be identified by the expression of biomarkers and intracellular pathways deeply involved in their malignant phenotype. Dissecting the molecular mechanisms underlying CSC biological functions might pave the way for novel therapeutic approaches. Herein, we highlight the intricate bidirectional communication between melanoma CSCs and their surrounding cells in the tumor microenvironment and discuss how this interplay might impact the processes of drug resistance and tumor relapse. We also address the potential benefits of CSC-targeted strategies, in combination with conventional drugs, for improving melanoma treatment strategies. Cutaneous melanoma still represents a significant health burden worldwide, being responsible for the majority of skin cancer deaths. Key advances in therapeutic strategies have significantly improved patient outcomes; however, most patients experience drug resistance and tumor relapse. Cancer stem cells (CSCs) are a small subpopulation of cells in different tumors, including melanoma, endowed with distinctive capacities of self-renewal and differentiation into bulk tumor cells. Melanoma CSCs are characterized by the expression of specific biomarkers and intracellular pathways; moreover, they play a pivotal role in tumor onset, progression and drug resistance. In recent years, great efforts have been made to dissect the molecular mechanisms underlying the protumor activities of melanoma CSCs to provide the basis for novel CSC-targeted therapies. Herein, we highlight the intricate crosstalk between melanoma CSCs and bystander cells in the tumor microenvironment (TME), including immune cells, endothelial cells and cancer-associated fibroblasts (CAFs), and its role in melanoma progression. Specifically, we discuss the peculiar capacities of melanoma CSCs to escape the host immune surveillance, to recruit immunosuppressive cells and to educate immune cells toward an immunosuppressive and protumor phenotype. We also address currently investigated CSC-targeted strategies that could pave the way for new promising therapeutic approaches for melanoma care. [ABSTRACT FROM AUTHOR]

Numerous human pathologies, such as neoplasia, are related to particular bacteria and changes in microbiome constituents. To investigate the association between an imbalance of bacteria and prostate carcinoma, the microbiome and gene functionality from tissues of patients with high-grade prostate tumor (HGT) and low-grade prostate tumor (LGT) were compared utilizing next-generation sequencing (NGS) technology. The results showed abnormalities in the bacterial profiles between the HGT and LGT specimens, indicating alterations in the make-up of bacterial populations and gene functionalities. The HGT specimens showed higher frequencies of Cutibacterium, Pelomonas, and Corynebacterium genera than the LGT specimens. Cell proliferation and cytokine assays also showed a significant proliferation of prostate cancer cells and elevated cytokine levels in the cells treated with Cutibacterium, respectively, supporting earlier findings. In summary, the HGT and LGT specimens showed differences in bacterial populations, suggesting that different bacterial populations might characterize high-grade and low-grade prostate malignancies. [ABSTRACT FROM AUTHOR]

PRF1 (perforin 1) is a key cytotoxic molecule that plays a crucial role in the killing function of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Recent studies have focused on PRF1's role in cancer development, progression, and prognosis. Studies have shown that aberrant PRF1 expression has a significant role to play in cancer development and progression. In some cancers, high expression of the PRF1 gene is associated with a better prognosis for patients, possibly because it helps enhance the body's immune response to tumors. However, some studies have also shown that the absence of PRF1 may make it easier for tumors to evade the body's immune surveillance, thus affecting patient survival. Furthermore, recent studies have explored therapeutic strategies based on PRF1, such as enhancing the ability of immune cells to kill cancer cells by boosting PRF1 activity. In addition, they have improved the efficacy of immunotherapy by modulating its expression to enhance the effectiveness of the treatment. Based on these findings, PRF1 may be a valuable biomarker both for the treatment of cancer and for its prognosis in the future. To conclude, PRF1 has an important biological function and has clinical potential for the treatment of cancer, which indicates that it deserves more research and development in the future. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) infection is common in tumor tissues across different types of cancer. While HCMV has not been recognized as a cancer-causing virus, numerous studies hint at its potential role in cancer development where its presence in various cancers corresponds with the hallmarks of cancer. Herein, we discuss and demonstrate that high-risk HCMV-DB and BL strains have the potential to trigger transformation in epithelial cells, including human mammary epithelial cells (HMECs), ovarian epithelial cells (OECs), and prostate epithelial cells (PECs), through the generation of polyploid giant cancer cells (PGCCs). A discussion is provided on how HCMV infection creates a cellular environment that promotes oncogenesis, supporting the continuous growth of CMV-transformed cells. The aforementioned transformed cells, named CTH, CTO, and CTP cells, underwent giant cell cycling with PGCC generation parallel to dedifferentiation, displaying stem-like characteristics and an epithelial–mesenchymal transition (EMT) phenotype. Furthermore, we propose that giant cell cycling through PGCCs, increased EZH2 expression, EMT, and the acquisition of malignant traits represent a deleterious response to the cellular stress induced by high-risk oncogenic HCMV strains, the latter being the origin of the transformation process in epithelial cells upon HCMV infection and leading to adenocarcinoma of poor prognosis. [ABSTRACT FROM AUTHOR]

The primary aim of this study was to evaluate the activation of the PERP and Akt oncogenes in the induction of skin cancer in FVB/N mice by a stepwise chemical process. Forty four-week-old female FVB/N mice were randomly divided into a control group (n = 8) and two experimental groups (group A: n = 16, group B: n = 16). In the study, the groups were subjected to a two-stage carcinogenesis procedure. This consisted of an initial application of 97.4 nmol DMBA to shaved skin on the back, followed by applications of 32.4 nmol TPA after thirteen weeks for group A and after twenty weeks for group B. The control group received no treatment. Skin conditions were monitored weekly for tumor development. At the end of the experiment, the animals were euthanized for further tissue sampling. Examination of the skin lesions in the experimental groups showed a correlation with tumor progression, ranging from dysplasia to carcinoma. Tumor samples were examined both histologically and immunohistochemically. Notably, and PERP expression was higher in precancerous than in malignant tumors. The differences in expression between precancerous and benign tumors provide further evidence of a role for PERP and Akt in the transition from benign to malignant states. Our findings underscore the critical roles of PERP and Akt in the pathogenesis of skin cancer and suggest their potential as biomarkers for early detection and targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Simple Summary: The mechanisms of renal cell carcinoma (RCC) progression are not well understood. There is a need to develop effective therapies against metastatic disease and to reduce high disease prevalence among minority and male populations. Here, we detail limited but compelling evidence for the role of the Hippo-YAP (Yes-associated protein)/TAZ (transcriptional coactivator with PDZ-binding motif) pathway in RCC progression. YAP/TAZ activation is evident in human RCC. Inhibition of YAP/TAZ in mice with kidney cancer mitigates neoplastic behavior, highlighting the therapeutic benefit of YAP/TAZ targeting in RCC. This review also summarizes, for the first time, upstream controls and oncogenic consequences associated with Hippo-YAP/TAZ dysregulation in progressive RCC. We describe critical literature gaps and future studies necessary to position the Hippo pathway among well-established drivers of kidney cancer progression. Although Hippo-YAP/TAZ pathway involvement has been extensively studied in the development of certain cancers, the involvement of this cascade in kidney cancer progression is not well-established and, therefore, will be the focus of this review. Renal cell carcinoma (RCC), the most prevalent kidney tumor subtype, has a poor prognosis and a high mortality rate. Core Hippo signaling inactivation (e.g., LATS kinases) leads to the nuclear translocation of YAP/TAZ where they bind to co-transcriptional factors such as TEAD promoting transcription of genes which initiates various fibrotic and neoplastic diseases. Loss of expression of LATS1/2 kinase and activation of YAP/TAZ correlates with poor survival in RCC patients. Renal-specific ablation of LATS1 in mice leads to the spontaneous development of several subtypes of RCC in a YAP/TAZ-dependent manner. Genetic and pharmacological inactivation of YAP/TAZ reverses the oncogenic potential in LATS1-deficient mice, highlighting the therapeutic benefit of network targeting in RCC. Here, we explore the unique upstream controls and downstream consequences of the Hippo-YAP/TAZ pathway deregulation in renal cancer. This review critically evaluates the current literature on the role of the Hippo pathway in RCC progression and highlights the recent scientific evidence designating YAP/TAZ as novel therapeutic targets against kidney cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck cancer disparities in outcomes for Black Americans have been well recognized. However, the specific drivers of the inferior outcomes remain poorly understood. We investigated the biologic features of patient oral cancers and performed a follow-up study of the patient post-surgery recurrences and metastases aiming to explore potential mechanisms that might underpin the poorer outcomes among Black American patients. It was found that high levels of tumor stemness and tumor-promoting stromal characteristics were linked to patient recurrence and metastasis. There were more cases of Black American than White American exhibiting high stemness traits and strong tumor-promoting stromal features associated with tumor recurrences and metastases, although the investigated cases displayed comparable clinical diagnoses. Our findings revealed that the differences in tumor stemness and stromal property among cancers with similar diagnoses contribute to patient outcome disparities. Black Americans (BAs) with head and neck cancer (HNC) have worse survival outcomes compared to the White patients. While HNC disparities in patient outcomes for BAs have been well recognized, the specific drivers of the inferior outcomes remain poorly understood. Here, we investigated the biologic features of patient tumor specimens obtained during the surgical treatment of oral cancers and performed a follow-up study of the patients' post-surgery recurrences and metastases with the aim to explore whether tumor biologic features could be associated with the poorer outcomes among BA patients compared with White American (WA) patients. We examined the tumor stemness traits and stromal properties as well as the post-surgery recurrence and metastasis of oral cancers among BA and WA patients. It was found that high levels of tumor self-renewal, invasion, tumorigenesis, metastasis, and tumor-promoting stromal characteristics were linked to post-surgery recurrence and metastasis. There were more BA than WA patients demonstrating high stemness traits and strong tumor-promoting stromal features in association with post-surgery tumor recurrences and metastases, although the investigated cases displayed clinically comparable TNM stages and histological grades. These findings demonstrated that the differences in tumor stemness and stromal property among cancers with comparable clinical diagnoses contribute to the outcome disparity in HNCs. More research is needed to understand the genetic and molecular basis of the biologic characteristics underlying the inferior outcomes among BA patients, so that targeting strategies can be developed to reduce HNC disparity. [ABSTRACT FROM AUTHOR]

Simple Summary: The connection between neurodegenerative diseases (NDs) and cancer has sparked a growing interest in biomedical research. Cancer cells show alterations in proteins linked to ND (tau, amyloid-β, α-synuclein, SOD1, and TDP-43). This review offers an updated summary of the biological role of these proteins in cancer. Specifically, we explore the effects of these proteins on cancer biology and how they affect these processes. Finally, we address the challenges and opportunities of targeting these proteins in the development of new cancer treatments. The link between neurodegenerative diseases (NDs) and cancer has generated greater interest in biomedical research, with decades of global studies investigating neurodegenerative biomarkers in cancer to better understand possible connections. Tau, amyloid-β, α-synuclein, SOD1, TDP-43, and other proteins associated with nervous system diseases have also been identified in various types of solid and malignant tumors, suggesting a potential overlap in pathological processes. In this review, we aim to provide an overview of current evidence on the role of these proteins in cancer, specifically examining their effects on cell proliferation, apoptosis, chemoresistance, and tumor progression. Additionally, we discuss the diagnostic and therapeutic implications of this interconnection, emphasizing the importance of further research to completely comprehend the clinical implications of these proteins in tumors. Finally, we explore the challenges and opportunities in targeting these proteins for the development of new targeted anticancer therapies, providing insight into how to integrate knowledge of NDs in oncology research. [ABSTRACT FROM AUTHOR]

Simple Summary: Individualized medicine means understanding how each tumor is different from normal cells and how each tumor is different from other tumors, including profiling mutations, non-mutational epigenetic changes, and differences in gene expression. This allows the discovery of key processes each tumor absolutely depends on for survival and growth, which are intrinsic weaknesses. This profiling means selecting treatments to specifically target each tumor's survival-dependent pathways, killing them. Tip60 is a master controller of processes that maintain genome stability and signaling regulating gene expression. While disrupted in many cancers, Tip60 is essential for cell survival, and inhibiting Tip60 kills tumors. While we understand some key aspects of the molecular roles Tip60 plays, much more remains to be discovered. A more complete understanding of the diverse roles and functions of Tip60 in cancer, and how targeting Tip60 kills cancer cells, will lead to better treatments for patients and increased survival. Precision (individualized) medicine relies on the molecular profiling of tumors' dysregulated characteristics (genomic, epigenetic, transcriptomic) to identify the reliance on key pathways (including genome stability and epigenetic gene regulation) for viability or growth, and then utilises targeted therapeutics to disrupt these survival-dependent pathways. Non-mutational epigenetic changes alter cells' transcriptional profile and are a key feature found in many tumors. In contrast to genetic mutations, epigenetic changes are reversable, and restoring a normal epigenetic profile can inhibit tumor growth and progression. Lysine acetyltransferases (KATs or HATs) protect genome stability and integrity, and Tip60 is an essential acetyltransferase due to its roles as an epigenetic and transcriptional regulator, and as master regulator of the DNA double-strand break response. Tip60 is commonly downregulated and mislocalized in many cancers, and the roles that mislocalized Tip60 plays in cancer are not well understood. Here we categorize and discuss Tip60-regulated genes, evaluate Tip60-interacting proteins based on cellular localization, and explore the therapeutic potential of Tip60-targeting compounds as epigenetic inhibitors. Understanding the multiple roles Tip60 plays in tumorigenesis will improve our understanding of tumor progression and will inform therapeutic options, including informing potential combinatorial regimes with current chemotherapeutics, leading to improvements in patient outcomes. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are mighty post-transcriptional regulators in cell physiology and pathophysiology. In this review, we focus on the role of miR-223-3p (henceforth miR-223) in various cancer types. MiR-223 has established roles in hematopoiesis, inflammation, and most cancers, where it can act as either an oncogenic or oncosuppressive miRNA, depending on specific molecular landscapes. MiR-223 has also been linked to either the sensitivity or resistance of cancer cells to treatments in a context-dependent way. Through this detailed review, we highlight that for some cancers (i.e., breast, non-small cell lung carcinoma, and glioblastoma), the oncosuppressive role of miR-223 is consistently reported in the literature, while for others (i.e., colorectal, ovarian, and pancreatic cancers, and acute lymphocytic leukemia), an oncogenic role prevails. In prostate cancer and other hematological malignancies, although an oncosuppressive role is frequently described, there is less of a consensus. Intriguingly, NLRP3 and FBXW7 are consistently identified as miR-223 targets when the miRNA acts as an oncosuppressor or an oncogene, respectively, in different cancers. Our review also describes that miR-223 was increased in biological fluids or their extracellular vesicles in most of the cancers analyzed, as compared to healthy or lower-risk conditions, confirming the potential application of this miRNA as a diagnostic and prognostic biomarker in the clinic. [ABSTRACT FROM AUTHOR]

Endothelial cells (ECs) are vital structural units of the cardiovascular system possessing two principal distinctive properties: heterogeneity and plasticity. Endothelial heterogeneity is defined by differences in tissue-specific endothelial phenotypes and their high predisposition to modification along the length of the vascular bed. This aspect of heterogeneity is closely associated with plasticity, the ability of ECs to adapt to environmental cues through the mobilization of genetic, molecular, and structural alterations. The specific endothelial cytoarchitectonics facilitate a quick structural cell reorganization and, furthermore, easy adaptation to the extrinsic and intrinsic environmental stimuli, known as the epigenetic landscape. ECs, as universally distributed and ubiquitous cells of the human body, play a role that extends far beyond their structural function in the cardiovascular system. They play a crucial role in terms of barrier function, cell-to-cell communication, and a myriad of physiological and pathologic processes. These include development, ontogenesis, disease initiation, and progression, as well as growth, regeneration, and repair. Despite substantial progress in the understanding of endothelial cell biology, the role of ECs in healthy conditions and pathologies remains a fascinating area of exploration. This review aims to summarize knowledge and concepts in endothelial biology. It focuses on the development and functional characteristics of endothelial cells in health and pathological conditions, with a particular emphasis on endothelial phenotypic and functional heterogeneity. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) entails a heterogenous neoplastic disease that arises from the mucosal epithelium of the upper respiratory system and the gastrointestinal tract. It is characterized by high morbidity and mortality, being the eighth most common cancer worldwide. It is believed that the mesenchymal/stem stromal cells (MSCs) present in the tumour milieu play a key role in the modulation of tumour initiation, development and patient outcomes; they also influence the resistance to cisplatin-based chemotherapy, the gold standard for advanced HNC. MSCs are multipotent, heterogeneous and mobile cells. Although no MSC-specific markers exist, they can be recognized based on several others, such as CD73, CD90 and CD105, while lacking the presence of CD45, CD34, CD14 or CD11b, CD79α, or CD19 and HLA-DR antigens; they share phenotypic similarity with stromal cells and their capacity to differentiate into other cell types. In the tumour niche, MSC populations are characterized by cell quiescence, self-renewal capacity, low reactive oxygen species production and the acquisition of epithelial-to-mesenchymal transition properties. They may play a key role in the process of acquiring drug resistance and thus in treatment failure. The present narrative review examines the links between MSCs and HNC, as well as the different mechanisms involved in the development of resistance to current chemo-radiotherapies in HNC. It also examines the possibilities of pharmacological targeting of stemness-related chemoresistance in HNSCC. It describes promising new strategies to optimize chemoradiotherapy, with the potential to personalize patient treatment approaches, and highlights future therapeutic perspectives in HNC. [ABSTRACT FROM AUTHOR]