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Purpose: Cervical screening is used to detect and treat precancers to prevent invasive cancers. However, successful prevention also requires adequate follow-up and treatment of individuals with abnormal screening results. The aim was to investigate demographics, clinical characteristics, and follow-up status for individuals needing colposcopy after an abnormal screening result. Methods: The STRIDES (Studying Risk to Improve DisparitiES) cohort comprises individuals undergoing cervical cancer screening and management at a Mississippi Health Department or University of Mississippi clinic. Follow-up status, demographics, and clinical data were assessed from electronic health records and, if necessary, patient navigation on individuals identified as needing a colposcopy after an abnormal screening. Results: Of the 1,458 individuals requiring colposcopy, 43.0% had the procedure within 4 months, 16.4% had a delayed procedure, and 39.5% had no documented colposcopy follow-up, with significant predictors of follow-up identified as age and cytology diagnosis. Individuals 30 + were more likely to have follow up with a colposcopy compared to individuals < 30 years (49% and 38.7%, respectively; p <.001). Individuals with cytology diagnoses of LSIL (52.9%), ASC-H (51.4%), and HSIL (62.3%) had higher percentages of adherence to follow-up guidelines (p <.001). In total, we found that 78% of individuals had some type of follow-up, including a repeat screening visit. Conclusion: Despite high cervical cancer screening rates among Mississippians, a substantial proportion did not have adequate next-step intervention. However, it is encouraging that highest risk individuals were more likely to have a colposcopy. Regardless, continuing to understand the underlying causes for incomplete follow-up is crucial for timely secondary targeted interventions to reduce cervical cancer burden, promote awareness, and improve health outcomes. [ABSTRACT FROM AUTHOR]

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths in women, with psychosocial stress commonly cited by patients as one of its causes. While there is conflicting epidemiological evidence investigating the association between psychosocial stress and breast cancer incidence and progression, there is reason to believe that interventions aimed at reducing stress pharmacologically or psychologically may improve breast cancer outcomes. The aim of this review is to discuss the molecular and biological mechanisms of stress-attributed breast cancer incidence and progression, including the induction of the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system (SNS), as well as decreased immune function and stress hormone-induced resistance to chemotherapy. Moreover, these mechanisms have been cited as potential therapeutic targets of pharmacologic and psychological interventions that may improve the care, well-being and survival of breast cancer patients. Further research is recommended to investigate whether interventions in the primary care setting for women with risk factors for breast cancer development may lead to a decreased incidence of invasive breast tumors. [ABSTRACT FROM AUTHOR]

Carcinogenesis is driven by complex molecular events, often involving key enzymes that regulate oxidative stress (OS). While classical enzymes such as SOD, catalase, and GPx have been extensively studied, other, non-classical oxidative stress-related enzymes (OSRE) may play critical roles in cancer progression. We aimed to explore the role of OSRE involved in an OS scenario and to assess their potential contribution to carcinogenesis in some of the most prevalent cancer types. Through data mining and bioinformatic analysis of gene and protein expression and mutation data, we identified OSRE with altered expression and mutations across cancer types. Functional pathways involving EGFR, MT-ND, GST, PLCG2, PRDX6, SRC, and JAK2 were investigated. Our findings reveal that enzymes traditionally considered peripheral to OS play significant roles in tumor progression. Those OSRE may contribute to cancer initiation and progression, as well as be involved with cancer hallmarks, such as EMT and invasion, proliferation, and ROS production. In addition, enzymes like SRC and JAK2 were found to have dual roles in both promoting ROS generation and being modulated by OS. OSRE also interact with key oncogenic signaling pathways, including Wnt/β-catenin and JAK2/STAT3, linking them to cancer aggressiveness and therapeutic resistance. Future research should focus on translating these findings into clinical applications, including the development of novel inhibitors or drugs targeting these non-classical enzymes. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) serve as crucial mediators of cell-to-cell communication in normal physiology as well as in diseased states; they have been largely studied in regard to their role in cancer progression. However, the mechanisms by which their biogenesis and secretion are regulated by metabolic or endocrine factors remain unknown. Here, we delineate a mechanism by which EV secretion is regulated by a cholesterol metabolite, 27-hydroxycholesterol (27HC), where treatment of myeloid immune cells (RAW 264.7 and J774A.1) with 27HC impairs lysosomal homeostasis, leading to shunting of multivesicular bodies (MVBs) away from lysosomal degradation, toward secretion as EVs. This altered lysosomal function is likely caused by mitochondrial dysfunction and subsequent increase in reactive oxygen species (ROS). Interestingly, cotreatment with a mitochondria-targeted antioxidant rescued the lysosomal impairment and attenuated the 27HC-mediated increase in EV secretion. Overall, our findings establish how a cholesterol metabolite regulates EV secretion and paves the way for the development of strategies to regulate cancer progression by controlling EV secretion. [ABSTRACT FROM AUTHOR]

The permeability of blood vessels plays a crucial role in the spread of cancer cells, facilitating their metastasis at distant sites. Small extracellular vesicles (sEVs) are known to contribute to the metastasis of various cancers by crossing the blood vessel wall. However, the role of abnormal glycoconjugates on sEVs in tumor blood vessels remains unclear. Our study found elevated levels of fucosyltransferase VII (FUT7) and its product sialyl Lewis X (sLeX) in muscle-invasive bladder cancer (BLCA), with high levels of sLeX promoting the growth and invasion of BLCA cells. Further investigation revealed that sLeX was enriched in sEVs derived from BLCA. sLeX-decorated sEVs increased blood vessel permeability by disrupting the tight junctions of human umbilical vein endothelial cells (HUVECs). Using the glycoproteomics approach, we identified integrin α3 (ITGA3) as a sLeX-bearing glycoprotein in BLCA cells and their sEVs. Mechanically, sLeX modification stabilized ITGA3 by preventing its degradation in lysosomes. sEVs carrying sLeX-modified ITGA3 can be effectively internalized by HUVECs, leading to a decrease in the expression of tight junction protein. Conversely, silencing ITGA3 in sLeX-decorated sEVs restored tight junction proteins and reduced blood vessel permeability by inhibiting the MAPK pathway. Moreover, sLeX-modification of ITGA3 at Asn 265 in HUVECs promoted occludin dephosphorylation at Ser/Thr residues, followed by inducing its importin α1-mediated nuclear translocation, which resulted in the disruption of tight junctions. Our findings suggest a potential strategy for disrupting the formation of a metastatic microenvironment and preventing the spread of malignant bladder cancer. [ABSTRACT FROM AUTHOR]

Estrogen receptor α (ERα) promotes the growth and survival of ER‐positive breast cancer (BC) cells. ER regulates ER expression target genes by directly binding to specific estrogen response elements, upon activation by estrogens. In this study, 106 proteins interacting with endogenous chromatin‐bound ER in a BC cell line MCF7 were identified using the RIME method. The interactome data showed that the tripartite motif containing 28 (TRIM28) is the most significantly enriched ER‐associated protein. This study provides evidence that TRIM28 expression improves ER transcriptional activity and promotes the BC cells proliferation, migration, and invasion of BC cells. The high expression of TRIM28 is associated with poor clinical outcomes in patients with ER‐positive BC. Mechanistic experiments indicate that TRIM28 expression activates the AKT/GSK3β pathway. To conclude, TRIM28 acts as a regulatory protein of ER and AKT signaling; therefore, it can be a target for the therapeutic interventions of BC. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer is characterized by aggressive peritoneal dissemination. Neutrophils are mobilized to peritoneal cavity in some patients with ovarian cancer dissemination; however, its pathological significance remains unknown. This study aimed to investigate the role of neutrophil extracellular traps (NETs) in ovarian cancer dissemination. We conducted a retrospective analysis of clinical data and samples from 340 patients with ovarian cancer who underwent primary surgery between 2007 and 2016 at the Osaka University Hospital. In vitro, NETs formation was induced by stimulating human peripheral neutrophils. The human ovarian cancer cell line, OVCAR8, was cocultured with NETs. For an ovarian cancer dissemination mouse model, we performed an intraperitoneal injection of OVCAR8 cells into nude mice. The association between NETs and peritoneal dissemination was explored, and model mice were treated with the PAD4 inhibitor GSK484 to assess antitumor efficacy. Neutrophilia (neutrophil count >7000/mm3) correlated with shorter survival, advanced peritoneal dissemination, elevated granulocyte colony-stimulating factor (G-CSF) levels, increased neutrophil count in ascites, and augmented NETs foci in peritoneal dissemination sites. In vitro assays revealed that G-CSF stimulated neutrophils to form NETs, promoting cancer cell adhesion. In vivo investigations revealed that G-CSF–producing tumor-bearing mice had accelerated peritoneal dissemination and poor prognosis. NETs formation was pathologically observed at the peritoneal dissemination sites. Inhibition of NETs formation by GSK484 significantly delayed peritoneal dissemination in vivo. In conclusion, G-CSF was associated with intra-abdominal NETs formation and increased peritoneal dissemination. NETs represent potential therapeutic targets for ovarian cancer, particularly in patients with neutrophilia. [ABSTRACT FROM AUTHOR]

Introduction: Incidence and mortality for bladder cancer has changed very little over the past 20 years. Approximately 40% of patients with high-risk nonmuscle invasive bladder cancer eventually recur/progress. It is important to understand the economic impact of disease recurrence/progression in bladder cancer. Our aim was to estimate and understand the direct costs associated with the treatment of bladder cancer from the payer's perspective in the USA, in the year of 2021, including costs for both newly diagnosed bladder cancer (stages 0a–IV) and recurrent patients. Methods: An economic model was constructed to calculate the number of patients receiving each treatment modality at every stage of disease and their respective costs. Epidemiological data were based on the CancerMPact Patient Metrics (PM) database and treatment modality data retrieved from CMP Treatment Architecture (TA), 2021 version. Resource utilization and costs were obtained from medical literature and public data sources. Only direct costs were considered. Results: There were an estimated 83,532 newly diagnosed patients with bladder cancer of all stages in 2021 with a projected total cost of treatment of ~$2.6 billion. Average cost per newly diagnosed patient varied from $19,521 (stage 0a) to $169,533 (metastatic disease). Cost profile differed substantially among the stages of disease. For the 75,760 patients that were expected to have a recurrence in 2021, an additional cost of ~$3.9 billion was estimated at an average cost per patient of $52,179. The expected total cost to treat newly diagnosed and newly recurrent patients is reported in this model, with the total cost in 2021 estimated to exceed $6.5 billion. Conclusions: Treatment and resource costs increase for bladder cancer as the disease recurs/progresses. More effective treatments that can delay recurrence/progression may reduce the economic burden associated with bladder cancer. Plain Language Summary: The costs of treating bladder cancer in the USA are high, expected to have exceeded $6.5 billion in the year 2021. The average cost for newly diagnosed patients ranges from $19,521 for the earliest stage of disease to $169,533 for metastatic disease. Average costs per patient increase upon disease recurrence and more effective initial treatments to delay disease recurrence or progression may reduce the costs associated with bladder cancer. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chemerin, which is a multifunctional cytokine and adipokine, has been implicated in inflammatory and metabolic processes and might play a role in upper gastrointestinal (GI) malignancies, particularly gastric and esophageal cancer. The aim of this review is to explore the role of chemerin in the pathophysiology of upper GI cancers, as well as its potential as a biomarker for early detection and as a therapeutic target. Methods: A comprehensive review of recent studies about chemerin's biochemical properties and interaction with its receptors, as well as its effects on inflammatory responses, immune regulation, and metabolic processes, was conducted. The clinical implications of chemerin for gastric and esophageal cancer were analyzed, whereas the potential therapeutic strategies targeting chemerin were discussed. Results: Elevated chemerin levels are associated with poor prognosis in gastric cancer and promote invasiveness and metastasis in esophageal cancer. Chemerin receptor antagonists show promising results in inhibiting cancer cell migration, invasion, and progression. Conclusions: Chemerin could represent a valuable prognostic biomarker and therapeutic target for upper GI cancers. Future observational studies should validate its clinical applications and investigate the efficacy of chemerin inhibitors as potential therapeutic targets. [ABSTRACT FROM AUTHOR]

The genesis and progression of tumors are multifaceted processes influenced by genetic mutations within the tumor cells and the dynamic interplay with their surrounding milieu, which incessantly impacts the course of cancer. The tumor microenvironment (TME) is a complex and dynamic entity that encompasses not only the tumor cells but also an array of non-cancerous cells, signaling molecules, and the extracellular matrix. This intricate network is crucial in tumor progression, metastasis, and response to treatments. The TME is populated by diverse cell types, including immune cells, fibroblasts, endothelial cells, alongside cytokines and growth factors, all of which play roles in either suppressing or fostering tumor growth. Grasping the nuances of the interactions within the TME is vital for the advancement of targeted cancer therapies. Consequently, a thorough understanding of the alterations of TME and the identification of upstream regulatory targets have emerged as a research priority. NF-kB transcription factors, central to inflammation and innate immunity, are increasingly recognized for their significant role in cancer onset and progression. This review emphasizes the crucial influence of the NF-kB signaling pathway within the TME, underscoring its roles in the development and advancement of cancer. By examining the interactions between NF-kB and various components of the TME, targeting the NF-kB pathway appears as a promising cancer treatment approach. [ABSTRACT FROM AUTHOR]

Galectin-9 (Gal-9) is a tandem-repeat galectin with diverse roles in immune homeostasis, inflammation, malignancy, and autoimmune diseases. In cancer, Gal-9 displays variable expression patterns across different tumor types. Its interactions with multiple binding partners, both intracellularly and extracellularly, influence key cellular processes, including immune cell modulation and tumor microenvironment dynamics. Notably, Gal-9 binding to cell-specific glycoconjugate ligands has been implicated in both promoting and suppressing tumor progression. Here, we provide insights into Gal-9 and its involvement in immune homeostasis and cancer biology with an emphasis on multiple myeloma (MM) pathophysiology, highlighting its complex and context-dependent dual functions as a pro- and anti-tumorigenic molecule and its potential implications for therapy in MM patients. [ABSTRACT FROM AUTHOR]

Background: Neutrophil extracellular traps (NETs) have long been consistently considered an innate immune defense against foreign pathogens, but this oversimplified view has decelerated the progression of perceiving NET biology in chronic diseases. It is now increasingly accepted that NETs are not exclusive to anti-infection responses, but are also central players with a double-edged sword role in cancer progression. NETs have gradually emerged as tumor diagnostic, predictive, and prognostic biomarkers, and strenuous endeavors have been devoted to tapping their potential as new therapeutic targets. Correspondingly, the boom in studies on NETs and tumors in recent years has achieved a series of scientific outputs, which opens up a new perspective for perceiving the sophisticated landscapes of the tumor immune microenvironment. However, there is still much room to translate NET-targeted immunotherapies into clinical practice. Therefore, it is necessary to explore the knowledge structure and latent hotspots of the links between NETs and tumors using bibliometric analysis. Methods: NETs and tumor publications from 2006 to 2024 were extracted from the Web of Science Core Collection. Bibliometric analysis and visualization were conducted using Microsoft Excel, VOSviewer, CiteSpace, and R-bibliometrix. Results: The analysis included 1,339 publications authored by 7,747 scholars affiliated with 1,926 institutions across 70 countries/regions with relevant articles published in 538 journals. Despite China's maximum number of publications, the United States has continued to dominate the field as a global cooperation center with overwhelming citation counts. Frontiers in Immunology published the most number of publications, whereas Blood was the most cited journal. Wagner, Denisa D. and Kaplan, Mariana J. are concurrently in both the top 10 most prolific authors and cited author lists. Tumor microenvironment and immunotherapy will likely be the focus of future research. Conclusions: A comprehensive bibliometric analysis was first conducted to map the current landscape and knowledge structure of the link between NETs and tumors in the hope of providing guidance and fresh perspectives for further research in this field. NETs are promising antitumor targets, and perhaps the eventual destination in the realm is to translate NET-targeted immunotherapies into clinical practice. [ABSTRACT FROM AUTHOR]

Background: Hyperprogressive disease (HPD) is a novel pattern of paradoxically rapid tumor progression, which often leads to early death, mostly in the first 2 months of treatment with immune checkpoint inhibitors (ICIs). Currently, there is no validated biomarker to assess patients at risk of HPD. Aim: The aim of this study was to systematically evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) in HPD and establish a reliable variable to support clinicians in defining personalized treatment strategies. Methods: PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases were searched for studies published before 31 December 2023. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of eligible studies. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects or a fixed-effects model to evaluate the association between the NLR and the risk of HPD. Results: A total of 17 studies with 2,964 patients were included for meta-analysis. The incidence of HPD across different types of tumors ranged from 6.3% to 35.6%. In the pooled analysis of the NLR and HPD, we identified that the NLR significantly associated with the risk of HPD (OR = 0.65; 95% CI: 0.46 to 0.91; p = 0.01) (I2 = 52%, p = 0.007). Conclusion: In the future, the NLR may serve as a remarkable biomarker for predicting the risk of HPD in clinical practice. [ABSTRACT FROM AUTHOR]

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Approximately 30%--40% of growth hormone--secreting pituitary adenomas (GHPAs) harbor somatic activating mutations in GNAS (α subunit of stimulatory G protein). Mutations in GNAS are associated with clinical features of smaller and less invasive tumors. However, the role of GNAS mutations in the invasiveness of GHPAs is unclear. GNAS mutations were detected in GHPAs using a standard polymerase chain reaction (PCR) sequencing procedure. The expression of mutation-associated maternally expressed gene 3 (MEG3) was evaluated with RT-qPCR. MEG3 was manipulated in GH3 cells using a lentiviral expression system. Cell invasion ability was measured using a Transwell assay, and epithelial--mesenchymal transition (EMT)-associated proteins were quantified by immunofluorescence and western blotting. Finally, a tumor cell xenograft mouse model was used to verify the effect of MEG3 on tumor growth and invasiveness. The invasiveness of GHPAs was significantly decreased in mice with mutated GNAS compared with that in mice with wild-type GNAS. Consistently, the invasiveness of mutant GNASexpressing GH3 cells decreased. MEG3 is uniquely expressed at high levels in GHPAs harboring mutated GNAS. Accordingly, MEG3 upregulation inhibited tumor cell invasion, and conversely, MEG3 downregulation increased tumor cell invasion. Mechanistically, GNAS mutations inhibit EMT in GHPAs. MEG3 in mutated GNAS cells prevented cell invasion through the inactivation of the Wnt/β-catenin signaling pathway, which was further validated in vivo. Our data suggest that GNAS mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the MEG3/Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

It has been shown that the high expression of human epididymis protein 4 (HE4) in most lung cancers is related to the poor prognosis of patients, but the mechanism of pathological transformation of HE4 in lung cancer is still unclear. The current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma (LUAD). Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies, and through analysis of The Cancer Genome Atlas (TCGA) dataset. Frequent HE4 overexpression was demonstrated in LUAD, but not in lung squamous cell carcinoma (LUSC), indicating that HE4 can serve as a biomarker to distinguish between LUAD and LUSC. HE4 knockdown significantly inhibited cell growth, colony formation, wound healing, and invasion, and blocked the G1-phase of the cell cycle in LUAD cell lines through inactivation of the EGFR signaling downstream including PI3K/AKT/mTOR and RAF/MAPK pathways. The first-line EGFR inhibitor gefitinib and HE4 shRNA had no synergistic inhibitory effect on the growth of lung adenocarcinoma cells, while the third-line EGFR inhibitor osimertinib showed additive anti-proliferative effects. Moreover, we provided evidence that HE4 regulated EGFR expression by transcription regulation and protein interaction in LUAD. Our findings suggest that HE4 positively modulates the EGFR signaling pathway to promote growth and invasiveness in LUAD and highlight that targeting HE4 could be a novel strategy for LUAD treatment. [ABSTRACT FROM AUTHOR]

Background/Aim: The dynamic interplay between cancer cells and the microenvironment involves a wide range of intricate relationships that evolve during different stages of tumor progression. Recent attention has focused on high endothelial venules (HEVs), specialized endothelial cells in tumors with a unique cuboidal shape similar to those in lymph nodes. Previous animal studies have shown that normalization of tumor angiogenesis through anti-VEGFR2 therapy promotes HEV formation. However, few reports exist regarding the relationship between HEVs and preexisting blood vessels or interstitial fibers. In this study, we histologically examined whether tumor vascular structure correlates with HEV neogenesis. Patients and Methods: A total of 109 patients with pathological stage I lung adenocarcinoma who had undergone curative lung resection at our Institute between 2012 and 2016 were included. HEVs were identified by anti-peripheral node addressin (PNAd) staining. Immunostaining and Elastica-Masson-Goldner staining were performed on tumor sections and quantified. Results: PNAd-positive cells were identified in 102 (93.6%) patients. Nearly all PNAd-positive cells were located within or near immune cell clusters. We investigated the correlation between microvessel structures or interstitial fibers and the number/density of PNAd-positive vessels, but no significant correlation was found. Since PNAd-positive cells were concentrated in immune cell aggregates, we focused our analysis specifically on these regions. Immune cell aggregates with abundant PNAd-positive vessels had a greater microvessel density along with by rich collagen fiber production, and displayed a more mature morphological phenotype of HEVs. Conclusion: The generation of PNAd-positive cells in tumors is governed by an angiogenetic mechanism distinct from that of broader tumor microenvironment. Furthermore, the accumulation of immune cells is associated with increased HEV maturation. [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma is a common pediatric solid tumor with poor outcomes in high-risk patients. The identification of new therapeutic biomarkers is critical for the treatment of disease. Methods: An analysis of large publicly available datasets of tumor gene expression was performed. In vivo studies were performed to elucidate the role of contactin-1 (CNTN1) in tumor progression. Results: Expression of the glycoprotein CNTN1 is elevated in neuroblastoma compared to other tumor types. CNTN1 expression is higher in stage 1 and non-MYCN-amplified tumors, compared to more aggressive stage 4 and MYCN-amplified tumors. Moreover, high CNTN1 expression is associated with increased overall survival in neuroblastoma patients. In vivo studies demonstrate reduced metastasis in mice xenografted with CNTN1 knockout tumors compared to wildtype. Conclusions: The results of this study suggest that CNTN1 is a potential biomarker and therapeutic target in neuroblastoma. Further investigation of CNTN1 could have significant clinical implications for improving neuroblastoma treatment. [ABSTRACT FROM AUTHOR]

Cancer remains a leading cause of mortality in Japan, yet participation in conventional screening programs is low due to invasiveness, cost, and accessibility. Non-invasive, affordable, and accurate methods for early cancer detection in asymptomatic individuals are urgently needed. This opinion manuscript evaluates nematode cancer testing, a novel urine-based screening test using the nematode Caenorhabditis elegans, for its potential to improve early cancer detection rates, based on real-world data published in a Japanese journal. Nematode cancer testing leverages the nematode's ability to detect cancer-associated volatile compounds in urine, offering a highly sensitive, non-invasive screening approach. We analyzed data from a nationwide survey of PET-equipped medical institutions in Japan, comparing cancer discovery rates between nematode cancer testing-triggered and standard PET screenings. In nematode cancer testing-triggered PET screenings, the cancer discovery rate was 2.96%, significantly higher than the 1.31% observed in standard PET screenings. The apparent positive predictive value (PPV) of nematode cancer testing was calculated at 2.09%; when adjusted for PET/CT sensitivity, the actual PPV increased to approximately 11.7%. This reflects a screening efficiency 14.6 times higher than the general population's cancer incidence. These findings indicate that nematode cancer testing successfully detects cancer in high-risk individuals and may encourage participation in further diagnostic evaluations. The recently published nationwide survey of PET-equipped medical institutions in Japan highlights the good performance of nematode cancer testing in cancer detection. As an opinion-type manuscript based on real-world data from Japan, this paper shows that nematode cancer testing has substantial potential as a cost-effective, minimally invasive primary cancer screening tool for asymptomatic populations. By enhancing early detection rates and screening efficiency, it addresses the limitations of traditional screening methods. Implementing nematode cancer testing could lead to improved cancer outcomes, particularly in populations with low participation in standard screening programs and resource-limited settings. [ABSTRACT FROM AUTHOR]

The Hippo pathway is highly evolved to maintain tissue homeostasis in diverse species by regulating cell proliferation, differentiation, and apoptosis. In tumor biology, the Hippo pathway is a prime example of signaling molecules involved in cancer progression and metastasis. Hippo core elements LATS1, LATS2, MST1, YAP, and TAZ have critical roles in the maintenance of traditional tissue architecture and cell homeostasis. However, in cancer development, dysregulation of Hippo signaling results in tumor progression and the formation secondary cancers. Hippo components not only transmit biochemical signals but also act as mediators of mechanotransduction pathways during malignant neoplasm development and metastatic disease. This review confers knowledge of Hippo pathway core components and their role in cancer progression and metastasis and highlights the clinical role of Hippo pathway in cancer treatment. The Hippo signaling pathway and its unresolved mechanisms hold great promise as potential therapeutic targets in the emerging field of metastatic cancer research. [ABSTRACT FROM AUTHOR]

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) is a prevalent and aggressive cancer with high rates of metastasis and poor prognosis. Recent research highlights the role of 5-methylcytosine (m5C) in cancer progression. NSUN2, an m5C methyltransferase, has been implicated in various cancers, but its role in HNSCC remains elusive. Methods: NSUN2 expression and its impact on HNSCC were analyzed by using clinical samples and bioinformatic analysis. m5C-Bis-Seq was used to assess changes in mRNA m5C modification and identify downstream targets. Both in vitro and vivo studies were performed to evaluate the impact of NSUN2 manipulation on tumor growth and metastasis. Results: Results indicated that NSUN2 was significantly upregulated in HNSCC tissues compared to normal tissues and was associated with poor prognosis. NSUN2 knockdown led to decreased cell proliferation, migration, and invasion in vitro and reduced tumorigenicity and lymph node metastasis in vivo. m5C-Bis-Seq revealed altered m5C-modification patterns upon NSUN2 knockdown, with LAMC2 identified as a key downstream target. Conclusions: NSUN2-mediated m5C-modification enhanced LAMC2 stability, promoting epithelial–mesenchymal transition (EMT) signaling pathways. These findings demonstrate that NSUN2 promotes the initiation and progression of HNSCC by stabilizing the LAMC2 transcript through m5C-dependent mechanisms, offering a promising epitranscriptomic-targeted therapeutic approach for HNSCC. [ABSTRACT FROM AUTHOR]

Oral bacteria naturally secrete extracellular vesicles (EVs), which have attracted attention for their promising biomedical applications including cancer therapeutics. However, our understanding of EV impact on tumor progression is hampered by limited in vivo models. In this study, we propose a facile in vivo platform for assessing the effect of EVs isolated from different bacterial strains on oral cancer growth and dissemination using the larval zebrafish model. EVs were isolated from: wild-type Aggregatibacter actinomycetemcomitans and its mutant strains lacking the cytolethal distending toxin (CDT) or lipopolysaccharide (LPS) O-antigen; and wild-type Porphyromonas gingivalis. Cancer cells pretreated with EVs were xenotransplanted into zebrafish larvae, wherein tumor growth and metastasis were screened. We further assessed the preferential sites for the metastatic foci development. Interestingly, EVs from the CDT-lacking A. actinomycetemcomitans resulted in an increased tumor growth, whereas EVs lacking the lipopolysaccharide O-antigen reduced the metastasis rate. P. gingivalis-derived EVs showed no significant effects. Cancer cells pretreated with EVs from the mutant A. actinomycetemcomitans strains tended to metastasize less often to the head and tail compared to the controls. In sum, the proposed approach provided cost- and labor-effective yet efficient model for studying bacterial EVs in oral carcinogenesis, which can be easily extended for other cancer types. Furthermore, our results support the notion that these nanosized particles may represent promising targets in cancer therapeutics. [ABSTRACT FROM AUTHOR]

Adult T‐cell leukemia (ATL) is an aggressive malignancy caused by human T‐cell leukemia virus type 1 (HTLV‐1) infection. Enhancer of zeste homolog 2 (EZH2) has been implicated in the development and progression of multiple cancers, including virus‐induced malignancies. However, the potential function of EZH2 in HTLV‐1‐induced oncogenesis has not been clearly elucidated. In the present study, we showed that EZH2 was overexpressed and activated in HTLV‐1‐infected cell lines, potentially due to the activation of EZH2 promoter by HTLV‐1 Tax and NF‐κB p65 subunit. In addition, we found that EZH2 enhanced the HBZ‐induced activation of TGF‐β signaling in a histone methyltransferase‐independent manner. As a mechanism for these actions, we found that EZH2 targeted Smad3/Smad4 to form a ternary complex, and the association between Smad3 and Smad4 was markedly enhanced in the presence of EZH2. Knockdown of EZH2 in ATL cells indeed repressed the expressions of the TGF‐β target genes. In particular, EZH2 synergistically enhanced the HBZ/TGF‐β‐induced Foxp3 expression. Treatment of 3‐Deazaneplanocin A, a specific inhibitor of EZH2 significantly inhibited the Foxp3 expression. Taken together, our results suggest that EZH2 may be involved in the differentiation of regulatory T cells through activating the HBZ‐Smad3‐TGF‐β signaling axis, which is considered to be a key strategy for viral persistence. [ABSTRACT FROM AUTHOR]

Introduction: Cervical mesonephric ductal adenocarcinoma (MA) is an HPV-independent adenocarcinoma that occurs in middle-aged women. MA originates from remnants of the Wolffian duct that usually regress in females once the induction of sex differentiation is activated. MA is a rare disease that accounts for less than 1% of all cervical adenocarcinomas. Clinical Case: We report a case of MA in which abdominal radical hysterectomy (ARH) was performed after neoadjuvant chemotherapy (NAC). The patient was a 66-year-old woman with abnormal genital bleeding. A colposcopy examination revealed macroscopic invasive cancer. A pelvic MRI scan revealed a 53 × 26 mm tumor in the cervix, and the histological diagnosis of the cervix was endometrioid carcinoma, with the diagnosis being cervical adenocarcinoma cT1b3N0M0. One course of NAC with paclitaxel-carboplatin (PC) was administered to shrink the tumor and stop the bleeding, and ARH was performed. Postoperative histopathological diagnosis was MA. The surgical margins of the resected specimen were negative, and NAC had been effective, so the patient underwent five courses of PC therapy after surgery. There has been no recurrence 12 months after surgery. Conclusions: There is no established standard treatment, but there are reports that PC therapy is effective. It is necessary to search for effective treatments by following up and accumulating further cases. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study investigated the association between the rs13306703 and rs8192288 variants of the superoxide dismutase 3 (SOD3) gene and breast cancer (BC) in the Mexican population, conducting both genetic and in silico analyses. Methods: 357 healthy women and 386 BC patients were studied using TaqMan assays, qPCR, and RFLP-PCR. Results: The TT genotype and a recessive pattern of these variants were risk factors for BC (p < 0.05). Specifically, the TT genotype of rs13306703 was associated with metastatic lymph nodes, tumor progression (III–IV), luminal A, nonresponse to chemotherapy, and ki-67 ≥ 20% with diabetes mellitus (DM). Meanwhile, the GT genotype of rs8192288 was associated with menopause, luminal A, tumor progression (III–IV), ki-67 ≥ 20%, and a positive estrogen receptor with nonresponse to chemotherapy. Additionally, the TT genotype combined with DM was identified as a BC risk factor (p < 0.05). The TT haplotype was also found to be a risk factor for BC. In silico analysis suggested that these variants might influence SOD3 regulation by affecting transcription factors and active enhancer sites. Conclusions: The rs13306703 and rs8192288 variants of the SOD3 gene were associated with an increased risk of BC and may alter SOD3 regulation through effects on transcription factors, active enhancers, and transcription start sites, with modified motifs in breast epithelium cells. [ABSTRACT FROM AUTHOR]

Objective: To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer. Methods: The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo. Results: Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G0/G1 phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05). Conclusion: Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer. [ABSTRACT FROM AUTHOR]

The correction notice addresses errors in figures in the original article "Pancreatic cancer-initiating cell exosome message transfer into noncancer-initiating cells: the importance of CD44v6 in reprogramming." The corrections made to Figures 3i, 4g, and 7f do not impact the overall results or conclusions of the paper. The corrected figures provide accurate representations of the data presented in the study, focusing on the effects of CIC-TEX treatment on RTK expression, downstream signaling molecules, and apoptosis resistance in pancreatic cancer cells. The study highlights the importance of CD44v6 in reprogramming and the potential implications for adjuvant pancreatic cancer therapy. [Extracted from the article]

Autophagy is an important lysosomal degradation process that digests and recycles bio-molecules, protein or lipid aggregates, organelles, and invaded pathogens. Autophagy plays crucial roles in regulation of metabolic and oxidative stress and multiple pathological processes. In cancer, the role of autophagy is dual and paradoxical. Ubiquitination has been identified as a key regulator of autophagy that can influence various steps in the autophagic process, with autophagy-related proteins being targeted for ubiquitination, thus impacting cancer progression and the effectiveness of therapeutic interventions. This review will concentrate on mechanisms underlying autophagy, ubiquitination, and their interactions in cancer, as well as explore the use of drugs that target the ubiquitin-proteasome system (UPS) and ubiquitination process in autophagy as part of cancer therapy. [ABSTRACT FROM AUTHOR]

ABSTRACT Lipid droplets are fat storage organelles composed of a protein envelope and lipid‐rich core. Regulation of this protein envelope underlies differential lipid droplet formation and function. In melanoma, lipid droplet formation has been linked to tumor progression and metastasis, but it is unknown whether lipid droplet proteins play a role. To address this, we performed proteomic analysis of the lipid droplet envelope in melanoma. We found that lipid droplet proteins were differentially enriched in distinct melanoma states; from melanocytic to undifferentiated. DHRS3, which converts all‐trans‐retinal to all‐trans‐retinol, is upregulated in the MITFLO/undifferentiated/neural crest‐like melanoma cell state and reduced in the MITFHI/melanocytic state. Increased DHRS3 expression is sufficient to drive MITFHI/melanocytic cells to a more undifferentiated/invasive state. These changes are due to retinoic acid‐mediated regulation of melanocytic genes. Our data demonstrate that melanoma cell state can be regulated by expression of lipid droplet proteins which affect downstream retinoid signaling. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) are present in the tumor microenvironment and can polarize into subtypes with different functions and characteristics in response to different stimuli, classifying them into antitumorigenic M1-type and pro-tumorigenic M2-type. The M1-type macrophages inhibit tumor growth through the release of pro-inflammatory cytokines, whereas the M2-type macrophages contribute to tumor progression through the promotion of tumor proliferation, angiogenesis and metastasis. Due to the duality of macrophage effects on tumors, TAMs have been a hot topic in tumor research. In this paper, the heterogeneity and plasticity of TAMs, the interactions between TAMs and other immune cells, and the effects of TAMs on tumors are reviewed, and the therapeutic strategies for TAMs are summarized and discussed. These therapeutic strategies encompass methods and approaches to inhibit the recruitment of TAMs, deplete TAMs, and modulate the polarization of TAMs. These studies help to deeply understand the mechanism of TAMs-tumor interaction and provide reference for combination therapy of tumors. [ABSTRACT FROM AUTHOR]

Background: Triple‐negative breast cancer, a subtype of breast cancer, is characterized by a poor prognosis. Recent studies have shown that miRNA30b acts as an oncogene and is vital for the proliferation of malignancies across various systems. This study aimed to elucidate the impact of miRNA30b on the proliferation, migration, and invasion capabilities of breast cancer cells in vitro. Methods: Triple‐negative breast cancer cell lines MDA‐MB‐231 were transiently transfected with miRNA30b inhibitor, mimic, or the negative control by Lipofectamine 2000. Successful transfection was confirmed by quantitative real‐time polymerase chain reaction (qRT‐PCR). Functional assays, including CCK8, clone formation, scratch, and transwell assays, were conducted to evaluate the proliferation, invasion, and migration ability of MDA‐MB‐231 cells in each group. The target protein of miRNA30b was determined using an online prediction data website, and the dual‐luciferase assay confirmed whether there was a binding site between miRNA30b and ADAM12. The effect was further verified by Western blot analysis. Results: MDA‐MB‐231 cells were transfected with miRNA30b inhibitor, mimic, and negative control. miRNA30b expression was downregulated in the cells. Relative to the negative control group, miRNA30b expression significantly increased in the mimic group and decreased in the miRNA30b inhibitor group, with the differences being statistically significant. The miRNA30b mimic group exhibited a significant increase in miRNA30b expression and a corresponding promotion of cell proliferation, colony formation, and migration. Conversely, the miRNA30b inhibitor group displayed significantly reduced miRNA30b expression and suppressed cell proliferation, colony formation, and migration abilities compared to the negative control cells. Bioinformatics software predicted ADAM12 as a potential target of miRNA30b. Dual‐luciferase assays confirmed the presence of a binding site between miRNA30b and ADAM12. Western blot analysis revealed that overexpression of miRNA30b downregulated ADAM12 expression in MDA‐MB‐231 cells. Conclusions: miRNA30b could promote proliferation, migration, and invasion of TNBC cell lines MDA‐MB‐231. The effect of miRNA30b on triple‐negative breast cancer would be achieved partly at least through inhibiting the expression of ADAM12. [ABSTRACT FROM AUTHOR]

Breast cancer is associated with high morbidity and mortality, which are closely influenced by protein post‐translational modifications (PTMs). Lysine crotonylation (Kcr) serves as a newly identified PTM type that plays a role in various biological processes; however, its involvement in breast cancer progression remains unclear. Minichromosome maintenance 6 (MCM6) is a critical component of DNA replication and has been previous confirmed to exhibit a significant role in tumorigenesis. Despite this, a comprehensive analysis of MCM6, particularly regarding its modifications in breast cancer is lacking. In this study, we found MCM6 is upregulated in breast invasive carcinoma (BRCA) and is associated with poorer overall survival by regulating the DNA damage repair mechanisms. Furthermore, MCM6‐knockdown resulted in decreased cell proliferation and inhibited the DNA replication, leading to DNA replication stress and sustained DNA damage, thereby enhancing the chemotherapeutic sensitivity of breast cancer. Additionally, SIRT7‐mediated crotonylation of MCM6 at K599 (MCM6‐K599cr) was significantly upregulated in response to DNA replication stress, primarily due to the disassemebly of the MCM2‐7 complex and regulated by RNF8‐mediated ubiquitination. Concurrently, kaempferol, which acts as a regulator of SIRT7, was found to enhance the Kcr level of MCM6, reducing tumour weight, particular when combined with paclitaxel, highlighting its potential chemotherapeutic target for BRCA therapy. [ABSTRACT FROM AUTHOR]

Tumor‐derived small extracellular vesicles (sEVs) are proven to play important roles in accelerating the progression of tumors. Destructing the sEVs at tumor sites is therefore a promising route to inhibit tumor progression. Herein, a smart DNA network‐based sEV trap (DNET) is reported, which achieved the specific capture of tumor‐derived sEVs through recognizing sEVs by polyaptamers, and the efficient destruction of sEVs via a photodynamic process at tumor sites. The DNET is constructed through the assembly of two DNA chains generated via rolling circle amplification. The DNA chains contain polyaptamers for capturing sEVs, polyvalent G‐quadruplexes for loading photodynamic reagents, and complementary segments for forming a cross‐linked network. Upon the irradiation of the laser, the captured sEVs in DNET are destructed, causing significant inhibition effects on the migration, invasion, and proliferation of glioblastoma cells. In particular, DNET achieved tumor inhibition rates of 39.70% in the zebrafish tumor model, and 73.10% in the nude mouse tumor model, respectively, demonstrating the significant efficacy of DNET in inhibiting tumor progression. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) presents a significant global health burden, with metastasis being the leading cause of treatment failure and mortality. NAT10, a regulatory protein involved in mRNA acetylation, has been implicated in various cancers. However, its role in GC, especially concerning metastasis and immune interactions, remains unclear. Utilizing multi‐omics data from gastric cancer samples, we conducted comprehensive analyses to investigate NAT10 expression, its correlation with clinical parameters and immune relevance. Bioinformatics analysis and digital image processing were employed for this purpose. Furthermore, in vitro and in vivo experiments were conducted to elucidate the functional role of NAT10 in gastric cancer progression, aiming to provide deeper biological insights. Our findings reveal a significant association between NAT10 expression and various aspects of transcriptional, protein, as well as tumor immunity in GC patients. Additionally, we demonstrated that NAT10 promotes gastric cancer cell proliferation and migration, both in cellular models and in animal studies, suggesting its involvement in early tumor microvascular metastasis. NAT10 emerges as a promising molecular target, offering potential avenues for further research into molecular mechanisms and therapeutic strategies for GC. [ABSTRACT FROM AUTHOR]

Age is a major risk factor for cancer, but how aging impacts tumor control remains unclear. In this study, we establish that aging of the immune system, regardless of the age of the stroma and tumor, drives lung cancer progression. Hematopoietic aging enhances emergency myelopoiesis, resulting in the local accumulation of myeloid progenitor-like cells in lung tumors. These cells are a major source of interleukin (IL)-1α, which drives the enhanced myeloid response. The age-associated decline of DNA methyltransferase 3A enhances IL-1α production, and disrupting IL-1 receptor 1 signaling early during tumor development normalized myelopoiesis and slowed the growth of lung, colonic, and pancreatic tumors. In human tumors, we identified an enrichment for IL-1α-expressing monocyte-derived macrophages linked to age, poorer survival, and recurrence, unraveling how aging promotes cancer and offering actionable therapeutic strategies. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Patients and Methods Results Conclusion Development of a prediction model using machine learning (ML) method for tumor progression in oral squamous cell carcinoma (OSCC) patients would provide risk estimation for individual patient outcomes.This predictive modeling study was conducted of 1163 patients with OSCC from Hospital of Stomatology, SYSU and SYSU Cancer Center from March 2009 to October 2021. Clinical, pathological, and hematological features of the patients were collected. Six ML algorithms were explored, and model performance was assessed by accuracy, sensitivity, specificity, f1 score, and AUC. SHAP values were used to identify the variables with the greatest contribution to the model.Among the 1163 patients (mean [SD] age, 55.36 [12.91] years), 563 are from development cohort and 600 are from validation cohort. The Logistic Regression algorithm outperformed all other models, with a sensitivity of 94.7% (68.2%), a specificity of 55.3% (63.7%), and the AUC of 0.76 ± 0.09 (0.723) in the development (validation) cohort. The most predictive feature was neutrophil count.This study demonstrated ML models can improve clinical prediction of oral squamous cell carcinoma progression through basic information of patients. These tools could be used to provide individual risk estimation and may help direct intervention. [ABSTRACT FROM AUTHOR]

Tumor heterogeneity and tumor evolution contribute to cancer treatment failure. To understand how selective pressures drive heterogeneous tumor evolution, it would be useful to image multiple important components and tumor subclones in vivo. We propose a supercontinuum-tailoring two-photon microscope (SCT-TPM) and realize simultaneous observation of nine fluorophores with a single light beam, breaking through the 'color barrier' of intravital two-photon fluorescence imaging. It achieves excitation multiplexing only by modulating the phase of fiber supercontinuum (SC), allowing to capture rapid events of multiple targets with maintaining precise spatial alignment. We employ SCT-TPM to visualize the spatiotemporal dynamics of heterogeneous tumor evolution under host immune surveillance, particularly the behaviors and interactions of six tumor subclones, immune cells and vascular network, and thus infer the trajectories of tumor progression and clonal competition. SCT-TPM opens up the possibility of tumor lineage tracking and mechanism exploration in living biological systems. Studying tumour heterogeneity and tumour evolution remains a challenging task. Here, the authors propose a supercontinuum-tailoring two-photon microscope to enable the imaging of multiple fluorophores with a single light beam. They use this tool to monitor the dynamics of heterogeneous tumour evolution. [ABSTRACT FROM AUTHOR]

This review explores the evolving landscape of gynecological oncology by focusing on emerging RNA modification signatures as promising biomarkers for assessing the risk and progression of ovarian, cervical, and uterine cancers. It provides a comprehensive overview of common RNA modifications, especially m6A, and their roles in cellular processes, emphasizing their implications in gynecological cancer development. The review meticulously examines specific m6A regulators including "writers", "readers", and "erasers" associated with three gynecological cancer types, discussing their involvement in initiation and progression. Methodologies for detecting RNA modifications are surveyed, highlighting advancements in high-throughput techniques with high sensitivity. A critical analysis of studies identifying m6A regulators as potential biomarkers is presented, addressing their diagnostic or prognostic significance. Mechanistic insights into RNA modification-mediated cancer progression are explored, shedding light on molecular pathways and potential therapeutic targets. Despite current challenges, the review discusses ongoing research efforts, future directions, and the transformative possibility of RNA modifications on early assessment and personalized therapy in gynecological oncology. [ABSTRACT FROM AUTHOR]

Protein tyrosine kinase 7 (PTK7) is an evolutionarily conserved transmembrane receptor and a specialized tyrosine kinase protein lacking kinase activity. PTK7 has been found to be strongly associated with a variety of diseases, including cancer. In this review, we will provide a comprehensive overview of the involvement of PTK7 in human cancer, focusing on the changing research landscape of PTK7 in cancer research, the molecular mechanisms of PTK7 involved in cancer progression, the targetability of PTK7 in cancer therapy, and the potential application of PTK7 in cancer management, thus demonstrating that PTK7 may be an underestimated contributor to human cancer. [ABSTRACT FROM AUTHOR]

The purpose of this research is to explore previous studies that investigated the body image of cancer patients and survivors by identifying the variables that have been examined and the gaps in the current research through a scoping review. The researchers conducted extensive and methodical searches in several databases using relevant keywords. After analyzing the full text of 89 papers, 45 studies were included in this review, published between 1995 and 2024. Most of the studies were conducted solely with female participants, and breast cancer was the most commonly researched cancer type. The researchers identified variables that affect the body image perspectives of this population, with the surgery method being the most frequently tested variable, followed by education level, age, cancer state, and mental health. This scoping review highlights the need to pay particular attention to a vulnerable group of under-educated female cancer patients who must undergo invasive cancer treatment. [ABSTRACT FROM AUTHOR]

As one of the most common malignancies, colorectal cancer (CRC) usually starts with a benign lesion and accumulates DNA damage as it progresses to full-fledged cancer. Glycyrrhizin (GL) has been found to alleviate tumor growth and inflammation, while the role of GL influences DNA damage response (DDR) in colorectal cancer remains unclear. GL exposure significantly reduced cell colony formation and viability with a concomitant increase in DNA fragmentation in CRC, meanwhile GL induced apoptosis by activating caspase-3. Moreover, GL induced cell cycle arrest in CRC cells at S phase, which was associated with decreased cyclin D1 in vitro. GL treatment significantly ameliorated tumor growth and promoted DDR in vivo. Mechanism analysis revealed that GL significantly downregulated the NHEJ pathway via inhibiting HMGB1. Finally, the expression of HMGB1 was abnormal regulated in CRC tissue than in adjacent normal tissues and associated with TNM stage and overall survival. Our findings indicate that HMGB1 may be a novel therapeutic target in CRC, a result that GL may serve as a promising drug for CRC treatment. [ABSTRACT FROM AUTHOR]

Interactions between tumoral cells and tumor‐associated bacteria within the tumor microenvironment play a significant role in tumor survival and progression, potentially impacting cancer treatment outcomes. In lung cancer patients, the Gram‐negative pathogen Pseudomonas aeruginosa raises questions about its role in tumor survival. Here, a microfluidic‐based 3D‐human lung tumor spheroid‐P. aeruginosa model is developed to study the bacteria's impact on tumor survival. P. aeruginosa forms a tumor‐associated biofilm by producing Psl exopolysaccharide and secreting iron‐scavenging pyoverdine, which is critical for establishing a bacterial community in tumors. Consequently, pyoverdine promotes cancer progression by reducing susceptibility to iron‐induced death (ferroptosis), enhancing cell viability, and facilitating several cancer hallmarks, including epithelial–mesenchymal transition and metastasis. A promising combinatorial therapy approach using antimicrobial tobramycin, ferroptosis‐inducing thiostrepton, and anti‐cancer doxorubicin could eradicate biofilms and tumors. This work unveils a novel phenomenon of cross‐kingdom cooperation, where bacteria protect tumors from death, and it paves the way for future research in developing antibiofilm cancer therapies. Understanding these interactions offers potential new strategies for combatting cancer and enhancing treatment efficacy. [ABSTRACT FROM AUTHOR]

Currently, despite the vast amounts of time and money invested in cancer treatment, cancer remains one of the primary threats to human life. The primary factor contributing to the low treatment efficacy is cancer heterogeneity. The unclear molecular mechanisms underlying tumorigenesis, coupled with the complexity of human physiology, and the inability of animal models to accurately replicate the human tumor microenvironment, pose significant hurdles in the development of novel cancer therapies. Tumor-microenvironment-on-chip (TMOC) represents a research platform that integrates three-dimensional cell culture with microfluidic systems, simulating the essential components and physiological traits of the in vivo tumor microenvironment. It offers a dynamic setting within the chip system to study tumor progression, potentially heralding a breakthrough in cancer research. In this review, we will summarize the current advancements in this platform, encompassing various types of TMOCs and their applications in different types of cancer. From our perspective, the TMOC platform necessitates enhanced integration with tissue engineering techniques and microphysiological environments before it can evolve into a more refined preclinical model for cancer research. [ABSTRACT FROM AUTHOR]

Air pollution significantly impacts lung cancer progression, but there is a lack of a comprehensive molecular characterization of clinical samples associated with air pollution. Here, we performed a proteogenomic analysis of lung adenocarcinoma (LUAD) in 169 female never-smokers from the Xuanwei area (XWLC cohort), where coal smoke is the primary contributor to the high lung cancer incidence. Genomic mutation analysis revealed XWLC as a distinct subtype of LUAD separate from cases associated with smoking or endogenous factors. Mutational signature analysis suggested that Benzo[a]pyrene (BaP) is the major risk factor in XWLC. The BaP-induced mutation hotspot, EGFR-G719X, was present in 20% of XWLC which endowed XWLC with elevated MAPK pathway activations and worse outcomes compared to common EGFR mutations. Multi-omics clustering of XWLC identified four clinically relevant subtypes. These subgroups exhibited distinct features in biological processes, genetic alterations, metabolism demands, immune landscape, and radiomic features. Finally, MAD1 and TPRN were identified as novel potential therapeutic targets in XWLC. Our study provides a valuable resource for researchers and clinicians to explore prevention and treatment strategies for air-pollution-associated lung cancers. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors, with high incidence and poor prognosis. Revealing mechanisms of ESCC progression and developing new therapeutic targets remains crucial. The aim of this study was to elucidate the molecular mechanism of miR‐30c‐5p in regulating the malignant progression of ESCC. Methods: TCGA, GEO, and other datasets were used to analyze the differential expression of miR‐30c‐5p in ESCC and adjacent tissues, and its impact on prognosis. Then the effects of miR‐30c‐5p on the proliferation, migration, and invasion of TE‐1 and Eca9706 cells were investigated through proliferation experiments, transwell and wounding healing assays. The regulatory mechanism of miR‐30c‐5p on the PI3K/AKT signaling pathway and its interaction in cancer progression were investigated through Western blots, dual‐luciferase reporter assay, and rescue experiments. Results: miR‐30c‐5p was significantly downregulated in ESCC tissue and represented a poor prognosis. miR‐30c‐5p mimic significantly inhibited the proliferation, migration, and invasion ability of ESCC, while miR‐30c‐5p inhibitor significantly promoted tumor cell progression. Through bioinformatic analysis and experimental results, miR‐30c‐5p interacted directly with PIK3CA mRNA and inhibited subsequent signaling pathway activation. PIK3CA activator could eliminate the inhibitory effects of miR‐30c‐5p mimic on the progression of ESCC, while PIK3CA inhibitors could rescue the promoting effect of miR‐30c‐5p inhibitor group cells. Conclusions: In summary, we found that miR‐30c‐5p inhibited the proliferation, invasion and migration of ESCC by inhibiting PI3K/AKT signaling pathway for the first time, and this study is expected to provide a novel insight and potential therapeutic target for managing ESCC. [ABSTRACT FROM AUTHOR]

The presence of microplastics within the human body has raised significant concerns about their potential health implications. Numerous studies have supported the hypothesis that the accumulation of microplastics can trigger inflammatory responses, disrupt the microbiome, and provoke immune reactions due to their physicochemical properties. Chronic inflammation, characterized by tissue damage, angiogenesis, and fibrosis, plays a crucial role in cancer development. It influences cancer progression by altering the tumor microenvironment and impairing immune surveillance, thus promoting tumorigenesis and metastasis. This review explores the fundamental properties and bioaccumulation of microplastics, as well as their potential role in the transition from chronic inflammation to carcinogenesis. Additionally, it provides a comprehensive overview of the associated alterations in signaling pathways, microbiota disturbances, and immune responses. Despite this, the current understanding of the toxicity and biological impacts of microplastics remains limited. To mitigate their harmful effects on human health, there is an urgent need to improve the detection and removal methods for microplastics, necessitating further research and elucidation. [ABSTRACT FROM AUTHOR]

Tumor hypoxia is a dynamic phenomenon marked by fluctuations in oxygen levels across both rapid (seconds to minutes) and slow (hours to days) time scales. While short hypoxia cycles are relatively well understood, the mechanisms behind longer cycles remain largely unclear. In this paper, we present a novel mechanistic mathematical model that explains slow hypoxia cycles through feedback loops involving vascular expansion and regression, oxygen-regulated tumor growth, and toxic cytokine production. Our study reveals that, for the emergence of slow hypoxia cycles, endothelial cells must adapt by decreasing receptor activation as ligand concentration increases. Additionally, the interaction between tumor cells and toxic cytokines influences frequency and intensity of these cycles. By examining the effects of pharmacological interventions, specifically poly (ADP-ribose) polymerase inhibitors, we also demonstrate how targeting cell proliferation can help regulate oxygen levels. Our findings enhance the understanding of hypoxia regulation and suggest PARP proteins as promising therapeutic targets. [ABSTRACT FROM AUTHOR]

Acute upper gastrointestinal bleeding (UGIB) is a medical emergency with most common cause being peptic ulcer disease (PUD) or variceal bleeding. However, cancers that cause UGIB by invading the small intestine are uncommon, and the invasion of renal cell carcinoma (RCC) into the duodenum is an even rarer occurrence. A 55‐year‐old male presented with melena and right flank pain. Esophagogastroduodenoscopy (EGD) revealed an active bleeding source in the duodenum, later identified on contrast‐enhanced computed tomography (CECT) as a duodenorenal fistula (DRF) caused by direct extension of the RCC. The imaging confirmed the presence of a malignant renal mass infiltrating adjacent organs. This atypical presentation of RCC with DRF manifesting as UGIB underscores the importance of comprehensive evaluations in cases of gastrointestinal bleeding to identify rare underlying causes. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Materials and Methods Results Conclusion Porphyromonas gingivalis (P. gingivalis) is a keystone periodontal pathogen associated with various gastro‐intestinal tract cancers. However, whether P. gingivalis can promote oral squamous cell carcinoma (OSCC) and the underlying mechanism associated with such promotion remain unclear.In this study, OSCC xenograft models were used to evaluate the effects of P. gingivalis on tumor progression. The functional studies were done on several OSCC cell lines in vitro. P. gingivalis‐specific 16S rRNA fluorescent in situ hybridization (FISH) was used to test its prevalence in clinical samples.We found that P. gingivalis increased tumor volume and tumor growth in OSCC nude models. Functional studies demonstrated that P. gingivalis inhibited the apoptosis of OSCC cells by promoting cellular autophagy. P. gingivalis was more prevalent in FISH samples from patients with OSCC than from patients with leukoplakia or healthy subjects (70% vs. 47.2% vs. 33.3%, p = 0.045 and p < 0.001, respectively).These data suggest that P. gingivalis plays an accelerating role in OSCC progression and contributes to OSCC by enhancing the autophagy pathway to reduce carcinoma apoptosis. [ABSTRACT FROM AUTHOR]

Cancer-associated adipocytes (CAAs) have emerged as pivotal players in various cancers, particularly in such as breast cancer, significantly influencing their progression and therapy resistance. Understanding the adipocytes/cancer cells crosstalk is crucial for effective treatment strategies. Raman spectroscopy, a label-free optical technique, offers potential for characterizing biological samples by providing chemical-specific information. In this study, we used Raman spectroscopy and Trajectory Inference methods, specifically the Partition-based graph abstraction algorithm, to investigate the interactions between 3T3-L1 differentiated adipocytes and MDA-MB-231 breast cancer cells in a 2D co-culture model. We demonstrate the existence of subpopulations of adipocytes and the molecular changes associated with CAAs phenotype. This work contributes to understanding the role of CAAs in breast cancer progression and may guide the development of targeted therapies disrupting this interaction. [ABSTRACT FROM AUTHOR]