Tumor Behavior Research Articles

The Evaluation of Tumor Budding in Oral Squamous Cell Carcinoma Arising in the Background of Oral Submucous Fibrosis.

Background and objective Oral submucous fibrosis (OSMF) is a common and potentially malignant disorder with a high risk of malignant transformation to oral squamous cell carcinoma (OSCC). Tumor budding is a scattered pattern of invasion and is related to the aggressive behavior of malignant tumors, increased depth of invasion, higher clinical staging, size, and grade of the tumor. The present study aimed to evaluate tumor budding in OSCCarising in the background of OSMF. Materials and methods A total of 120 patients with OSCC (30 each of OSCC arising in the background of OSMF, well-differentiated, moderately differentiated, and poorly differentiated OSCC) were included in the study. Hematoxylin and eosin (H&E)-stained sections were evaluated for the presence of tumor buds at the invasive front of the tumor. Kappa statistics and chi-square tests were employed to statistically compare the results by using IBM SPSS Statistics 23 software (IBM Corp., Armonk, NY). A p-value of less than or equal to 0.05 was considered statistically significant. Results The mean age of the occurrence of OSCC arising in the background of OSMF was 45.3 ±7.62 years. A progressive increase in the tumor buds was noted in OSCC arising in the background of OSMF, well-differentiated squamous cell carcinoma (WDSCC), moderately differentiated squamous cell carcinoma (WDSCC), and poorly differentiated squamous cell carcinoma (PDSCC). The chi-square test showed no significant difference between OSCC in the setting of OSMF and WDSCC (p=0.604) groups; however, a significant difference was noted with MDSCC (p=0.001) and PDSCC (p=0.000) groups. Conclusions OSCC arising in the background of OSMF shows lower tumor budding at the invasive front of the tumor. This histopathological parameter can be easily identified in the H&E sections and is fairly reproducible. Hence, reporting the presence of tumor budding will help in predicting the prognosis of these patients.

The Role of Tissue Factor In Signaling Pathways of Pathological Conditions and Angiogenesis.

Tissue factor (TF) is an integral transmembrane protein associated with the extrinsic coagulation pathway. TF gene expression is regulated in response to inflammatory cytokines, bacterial lipopolysaccharides, and mechanical injuries. TF activity may be affected by phosphorylation of its cytoplasmic domain and alternative splicing. TF acts as the primary initiator of physiological hemostasis, which prevents local bleeding at the injury site. However, aberrant expression of TF, accompanied by the severity of diseases and infections under various pathological conditions, triggers multiple signaling pathways that support thrombosis, angiogenesis, inflammation, and metastasis. Protease-activated receptors (PARs) are central in the downstream signaling pathways of TF. In this study, we have reviewed the TF signaling pathways in different pathological conditions, such as wound injury, asthma, cardiovascular diseases (CVDs), viral infections, cancer and pathological angiogenesis. Angiogenic activities of TF are critical in the repair of wound injuries and aggressive behavior of tumors, which are mainly performed by the actions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF1-α). Pro-inflammatory effects of TF have been reported in asthma, CVDs and viral infections, including COVID-19, which result in tissue hypertrophy, inflammation, and thrombosis. TF-FVII induces angiogenesis via clotting-dependent and -independent mechanisms. Clottingdependent angiogenesis is induced via the generation of thrombin and cross-linked fibrin network, which facilitate vessel infiltration and also act as a reservoir for endothelial cells (ECs) growth factors. Expression of TF in tumor cells and ECs triggers clotting-independent angiogenesis through induction of VEGF, urokinase-type plasminogen activator (uPAR), early growth response 1 (EGR1), IL8, and cysteine-rich angiogenic inducer 61 (Cyr61).

Progress of Cancer Stem Cells in Retinoblastoma.

The theory of cancer stem cells is a breakthrough discovery that offers exciting possibilities for comprehending the biological behavior of tumors. More and more evidence suggests that retinoblastoma cancer stem cells promote tumor growth and are likely to be the origin of tumor formation, drug resistance, recurrence, and metastasis. At present, some progress has been made in the verification, biological behavior, and drug resistance mechanism of retinoblastoma cancer stem cells. This article aims to review the relevant research and explore future development direction.

Advanced tumor growth modeling: A numerical study integrating phase plane analysis with finite volume method

This study investigates tumor density dynamics through computational modeling, focusing on key parameters: proliferation rate m, diffusion coefficient τ, and additional factors c and κ. Systematic exploration reveals nuanced interactions shaping tumor growth, regression, and dispersal. Higher m values accelerate proliferation, while increased τ facilitates dispersal. Parameters c and κ further refine our understanding of tumor behavior. These insights inform the development of computational models for oncological research, with implications for targeted therapeutic interventions. The aim can be realized by utilizing the propose Finite Volume Method to develop a representation of cancer models and improve the efficiency of their simulations. Furthermore, the numerical results will be validated by comparing them with the Tanh-Coth method formulation to assess the model's accuracy and efficiency. The findings suggest that accurate modeling of tumor dynamics can aid in predicting tumor progression and response to treatments, ultimately contributing to personalized medicine and more effective therapeutic strategies. Phase plane analysis shows the schemes are conditionally stable and accurate to the fourth order in time. The method demonstrates exceptional agreement and error-free findings compared to 3D plots, underscoring its potential utility in clinical and research settings.

The 2022 WHO classification of tumors of the pituitary gland: An update on aggressive and metastatic pituitary neuroendocrine tumors.

The vast majority of pituitary neuroendocrine tumors (PitNETs) are benign and slow growing with a low relapse rate over many years after surgical resection. However, about 40% are locally invasive and may not be surgically cured, and about one percentage demonstrate an aggressive clinical behavior. Exceptionally, these aggressive tumors may metastasize outside the sellar region to the central nervous system and/or systemically. The 2017 (4th Edition) WHO Classification of Pituitary Tumors abandoned the terminology "atypical adenoma" for tumors previously considered to have potential for a more aggressive behavior since its prognostic value was not established. The 2022 (5th Edition) WHO Classification of the Pituitary Tumors emphasizes the concept that morphological features distinguish indolent tumors from locally aggressive ones, however, the proposed histological subtypes are not consistent with the real life clinical characteristics of patients with aggressive tumors/carcinomas. So far, no single clinical, radiological or histological parameter can determine the risk of growth or malignant progression. Novel promising molecular prognostic markers, such as mutations in ATRX, TP53, SF3B1, and epigenetic DNA modifications, will need to be verified in larger tumor cohorts. In this review, we provide a critical analysis of the WHO guidelines for prognostic stratification and diagnosis of aggressive and metastatic PitNETs. In addition, we discuss the new WHO recommendations for changing ICD-O and ICD-11 codes for PitNET tumor behavior from a neoplasm either "benign" or "unspecified, borderline, or uncertain behavior" to "malignant" neoplasm regardless of the clinical presentation, histopathological subtype, and tumor location. We encourage multidisciplinary initiatives for integrated clinical, histological and molecular classification, which would enable early recognition of these challenging tumors and initiation of more appropriate and aggressive treatments, ultimately improving the outcome.

SLAM family-mediated crosstalk between tumor and immune cells in the tumor microenvironment: a promising biomarker and a potential therapeutic target for immune checkpoint therapies.

Immune cells infiltrating the tumor microenvironment are physiologically important in controlling cancers. However, emerging studies have shown that cancer cells can evade immune surveillance and establish a balance in which these immune cells support tumor progression and therapeutic resistance. The signaling lymphocytic activation molecule family members have been recognized as mediators of tumor microenvironment interactions, and a promising therapeutic target for cancer immunotherapy. This review is focused on the role of SLAM family in tumor and immune cell interactions and discusses how such crosstalk affects tumor behavior. This will shed insight into the next step toward improving cancer immunotherapy.

Prognostic and Clinical Significance of the Proliferation Marker MCM7 in Breast Cancer.

Minichromosome maintenance complex component 7 (MCM7) plays an essential role in proliferation and DNA replication of cancer cells. However, the expression and prognostic significance of MCM7 in breast cancer (BC) remain to be defined. In this study, we aimed to evaluate the role of MCM7 in BC. We conducted immunohistochemistry staining of MCM7 in 1,156 operable early-stage BC samples and assessed MCM7 at the transcriptomic levels using publicly available cohorts (n = 13,430). MCM7 expression was evaluated and correlated with clinicopathological parameters including Ki67 labelling index and patient outcome. At the transcriptomic level, there was a significant association between high MCM7 mRNA levels and shorter patient survival in the whole cohort and in luminal BC class but not in the basal-like molecular subtype. High MCM7 protein expression was detected in 43% of patients and was significantly associated with parameters characteristic of aggressive tumour behaviour. MCM7 was independently associated with shorter survival, particularly in oestrogen receptor-positive (luminal) BC. MCM7 stratified luminal tumours with aggressive clinicopathological features into distinct prognostic groups. In endocrine therapy-treated BC patients, high MCM7 was associated with poor outcome, but such association disappeared with administration of adjuvant chemotherapy. Patients with high expression of Ki67 and MCM7 showed worst survival, while patients with double low expression BC showed the best outcome compared with single expression groups. The current findings indicate that MCM7 expression has a prognostic value in BC and can be used to identify luminal BC patients who can benefit from adjuvant chemotherapy.

An attempt to identify brain tumour tissue in neurosurgery by mechanical indentation measurements

BackgroundThe intraoperative differentiation between tumour tissue, healthy brain tissue, and any sensitive structure of the central nervous system is carried out in modern neurosurgery using various multimodal technologies such as neuronavigation, fluorescent dyes, intraoperative ultrasound or the use of intraoperative MRI, but also the haptic experience of the neurosurgeon. Supporting the surgeon by developing instruments with integrated haptics could provide a further objective dimension in the intraoperative recognition of healthy and diseased tissue.MethodsIn this study, we describe intraoperative mechanical indentation measurements of human brain tissue samples of different tumours taken during neurosurgical operation and measured directly in the operating theatre, in a time frame of maximum five minutes. We present an overview of the Young’s modulus for the different brain tumour entities and potentially differentiation between them.ResultsWe examined 238 samples of 75 tumour removals. Neither a clear distinction of tumour tissue against healthy brain tissue, nor differentiation of different tumour entities was possible on solely the Young’s modulus. Correlation between the stiffness grading of the surgeon and our measurements could be found.ConclusionThe mechanical behaviour of brain tumours given by the measured Young’s modulus corresponds well to the stiffness assessment of the neurosurgeon and can be a great tool for further information on mechanical characteristics of brain tumour tissue. Nevertheless, our findings imply that the information gained through indentation is limited.

Integrating Proteomic Analysis and Machine Learning to Predict Prostate Cancer Aggressiveness

Prostate cancer (PCa) poses a significant challenge because of the difficulty in identifying aggressive tumors, leading to overtreatment and missed personalized therapies. Although only 8% of cases progress beyond the prostate, the accurate prediction of aggressiveness remains crucial. Thus, this study focused on studying retinoblastoma phosphorylated at Serine 249 (Phospho-Rb S249), N-cadherin, β-catenin, and E-cadherin as biomarkers for identifying aggressive PCa using a logistic regression model and a classification and regression tree (CART). Using immunohistochemistry (IHC), we targeted the expression of these biomarkers in PCa tissues and correlated their expression with clinicopathological data of the tumor. The results showed a negative correlation between E-cadherin and β-catenin with aggressive tumor behavior, whereas Phospho-Rb S249 and N-cadherin positively correlated with increased tumor aggressiveness. Furthermore, patients were stratified based on Gleason scores and E-cadherin staining patterns to evaluate their capability for early identification of aggressive PCa. Our findings suggest that the classification tree is the most effective method for measuring the utility of these biomarkers in clinical practice, incorporating β-catenin, tumor grade, and Gleason grade as relevant determinants for identifying patients with Gleason scores ≥ 4 + 3. This study could potentially benefit patients with aggressive PCa by enabling early disease detection and closer monitoring.

Chimeric peptide-engineered immunostimulant for endoplasmic reticulum targeted photodynamic immunotherapy against metastatic tumor

The combination of therapy-induced immunogenic cell death (ICD) and immune checkpoint blockade can provide a mutually reinforced strategy to reverse the poor immunogenicity and immune escape behavior of tumors. In this work, a chimeric peptide-engineered immunostimulant (ER-PPB) is fabricated for endoplasmic reticulum (ER)-targeted photodynamic immunotherapy against metastatic tumors. Among which, the amphiphilic chimeric peptide (ER-PP) is composed of ER-targeting peptide FFKDEL, hydrophilic PEG8 linker and photosensitizer protoporphyrin IX (PpIX), which could be assembled with a PD-1/PD-L1 blocker (BMS-1) to prepare ER-PPB. After passively targeting at tumor tissues, ER-PPB will selectively accumulate in the ER. Next, the localized PDT of ER-PPB will produce a lot of ROS to destroy the primary tumor cells, while increasing the ER stress to initiate a robust ICD cascade. Moreover, the concomitant delivery of BMS-1 can impede the immune escape of tumor cells through PD-1/PD-L1 blockade, thus synergistically activating the immune system to combat metastatic tumors. In vitro and in vivo results demonstrate the robust immune activation and metastatic tumor inhibition characteristics of ER-PPB, which may offer a promising strategy for spatiotemporally controlled metastatic tumor therapy.

Evaluating trophinin associated protein as a biomarker of prognosis and therapy response in renal cell carcinoma

BackgroundTrophinin Associated Protein (TROAP) has been implicated in some tumors, yet its role in renal cell carcinoma (RCC) remains underexplored. This study aims to elucidate the prognostic and therapeutic implications of TROAP in RCC, encompassing different subtypes.MethodsFirstly, we identified the expression patterns of TROAP across various tumors within the TCGA pan-cancer cohort. Subsequently, the prognostic significance of TROAP was validated in three TCGA RCC cohorts and a local cohort. Finally, we conducted functional enrichment analysis, somatic mutations and copy number variations, assessed therapeutic response cohorts, and performed in vitro experiments to explore the biological characteristics of TROAP.ResultsTROAP serves as an unfavorable factor in both the TCGA RCC datasets and our local cohort. Functional enrichment analysis and in vitro experiments have demonstrated its oncogene effect in promoting tumor progression. Additionally, the relationship between TROAP expression and gene mutations in RCC appears to be limited. Furthermore, elevated TROAP expression is associated with reduced efficacy of RCC therapies, including nivolumab and everolimus.ConclusionsOur findings illustrate TROAP as a pivotal biomarker for prognosis and therapeutic response in RCC. Elevated TROAP expression is indicative of aggressive tumor behavior and resistance to conventional therapies, making it a valuable target for personalized treatment strategies in RCC management.

Advances in Melanoma: From Genetic Insights to Therapeutic Innovations.

Advances in melanoma research have unveiled critical insights into its genetic and molecular landscape, leading to significant therapeutic innovations. This review explores the intricate interplay between genetic alterations, such as mutations in BRAF, NRAS, and KIT, and melanoma pathogenesis. The MAPK and PI3K/Akt/mTOR signaling pathways are highlighted for their roles in tumor growth and resistance mechanisms. Additionally, this review delves into the impact of epigenetic modifications, including DNA methylation and histone changes, on melanoma progression. The tumor microenvironment, characterized by immune cells, stromal cells, and soluble factors, plays a pivotal role in modulating tumor behavior and treatment responses. Emerging technologies like single-cell sequencing, CRISPR-Cas9, and AI-driven diagnostics are transforming melanoma research, offering precise and personalized approaches to treatment. Immunotherapy, particularly immune checkpoint inhibitors and personalized mRNA vaccines, has revolutionized melanoma therapy by enhancing the body's immune response. Despite these advances, resistance mechanisms remain a challenge, underscoring the need for combined therapies and ongoing research to achieve durable therapeutic responses. This comprehensive overview aims to highlight the current state of melanoma research and the transformative impacts of these advancements on clinical practice.

Characterization of estrogen receptor mutant breast cancer in 3D cell culture.

14 Background: Breast cancer is a leading cancer in women worldwide. Many primary breast cancers are estrogen receptor positive (ER+) and responsive to anti-estrogenic therapies. These tumors can mutate estrogen receptors to survive, allowing the tumors to become more triple-negative-like and therefore more dangerous. Triple-negative breast cancer (TNBC) has been particularly challenging to treat due to its lack of estrogen (ER), progesterone (PR), and human epidermal growth factor (HER2) receptors. Due to the lack of treatment options, TNBC has a poor prognosis and contributes to a significant percentage of breast cancer mortalities. These ER mutants act more like TNBC, resulting in worse clinical outcomes. Current research on these ER mutants has been conducted using two-dimensional (2D), monolayer cell culture, which does not translate effectively in animal models, and ultimately, humans. Three-dimensional (3D) cell culture, which allows for the formation of spheroids, mimics actual tumors and provides results more consistent with tumor treatment in vitro. Due to the lack of research on these ER mutants in 3D culture, they must be characterized to determine baseline gene expression and behavior. After characterization, identifying changes resulting from drug treatment will be possible. Methods: Parental, ER+ MCF7-Luc cells, and daughter D538G and Y537S mutants were seeded at a density of 3000 cells/well in a low-attachment, round-bottomed 96-well plate. 48 hours and 7 days post-seeding, newly-formed spheroids were imaged. Using ImageJ analysis software, diameter, area, perimeter, circularity, aspect ratio, roundness, and solidity were determined. After 7 days in culture, spheres were collected for RNA extraction. Next, cDNA was synthesized, and qRT-PCR was performed to assess gene expression differences. Results: The wild-type ER+ spheres have smaller diameters, spherocity values closer to one, and are more compact. They express different levels of EMT markers from the controls, indicating alterations to signaling pathways. These 3D cultures vary in expression from the 2D cultures of the same cell lines. Conclusions: MCF-7 ER+ breast cancer cells aggregate more readily than ER+ mutants. The ER must be involved in signaling that promotes aggregation, as reduced ER signaling decreases the ability for spheroid formation. This phenomenon and the differences in gene expression may explain why mutants tend to behave in a more triple-negative manner. Cells cultured in 3D express some genes to different extents, confirming the importance of 3D culture for identifying future therapies – cells behave differently in different culturing contexts, 3D being more consistent with tumor behavior. Therefore, characterizing ER+ mutants prior to drug treatment studies is crucial to understanding how compounds affect cancer cells, as well as for identifying differences in various ER+ mutants for better treatment outcomes.

A Review on Canine and Human Soft Tissue Sarcomas: New Insights on Prognosis Factors and Treatment Measures.

Soft tissue sarcomas (STSs) represent a diverse group of tumors arising from mesenchymal cells, affecting both humans and animals, including dogs. Although STSs represent a class of rare tumors, especially in humans, they pose significant clinical challenges due to their potential for local recurrence and distant metastasis. Dogs, as a model for human STSs, offer several advantages, including exposure to similar environmental risk factors, genetic diversity among breeds, and the spontaneous development of tumors. Furthermore, canine tumors closely mimic the heterogeneity and complexity of human tumors, making them valuable for research into disease progression and treatment effectiveness. Current treatment approaches for STSs in both dogs and humans primarily involve surgery, radiation therapy, and chemotherapy, with treatment decisions based on tumor characteristics and patient factors. However, the development of novel therapeutic strategies is essential, given the high failure rate of new drugs in clinical trials. To better design new tailored treatments, comprehension of the tumor microenvironment (TME) is fundamental, since it plays a crucial role in STS initiation and progression by modulating tumor behavior, promoting angiogenesis, and suppressing immune responses. Notably, TME features include cancer-associated fibroblasts (CAFs), extracellular matrix (ECM) alterations, and tumor-associated macrophages (TAMs) that, depending on their polarization state, can affect immune responses and thus the patient's prognosis. In this review, new therapeutical approaches based on immunotherapy will be deeply explored as potential treatment options for both dogs and humans with STSs. In conclusion, this review provides an overview of the current understanding of STSs in dogs and humans, emphasizing the importance of the TME and potential treatment strategies.

Molecular GBM versus Histopathological GBM: Radiology-Pathology-Genetic Correlation and the New WHO 2021 Definition of Glioblastoma.

Given the recent advances in molecular pathogenesis of tumors, with better correlation with tumor behavior and prognosis, major changes were made to the new 2021 World Health Organization (WHO) classification of CNS tumors, including updated criteria for diagnosis of glioblastoma (GBM). Diagnosis of GBM now requires absence of isocitrate dehydrogenase and histone 3 mutations (IDH-wild-type and H3-wild-type) as the basic cornerstone, with elimination of the IDH-mutant category. The requirements for diagnosis were conventionally histopathological, based on the presence of pathognomonic features such as microvascular proliferation and necrosis. However, even if these histologic features are absent, many lower-grade (WHO grade 2/3) diffuse astrocytic gliomas behave clinically similar to GBM (grade 4). The 2021 WHO classification introduced new molecular criteria that can be used to upgrade the diagnosis of such histologically lower-grade, IDH-wild-type, astrocytomas to GBM. The 3 molecular criteria include: concurrent gain of whole chromosome 7 and loss of whole chromosome 10 (+7/-10); telomerase reverse transcriptase promoter mutation; and epidermal growth factor receptor amplification. Given these changes, it is now strongly recommended to have molecular analysis of WHO grade 2/3 diffuse astrocytic, IDH-wild-type, gliomas in adult patients, as identification of any of the above mutations allows for upgrading the tumor to WHO grade 4 ("molecular GBM") with important prognostic implications. Despite an early stage, there is active ongoing research on the unique MR imaging features of molecular GBM. This paper highlights the differences between "molecular" and "histopathological" GBM, with the aim of providing a basic understanding about these changes.

Impact of microRNA variants on PI3K/AKT signaling in triple-negative breast cancer: comprehensive review.

Breast cancer (BC) is a significant cause of cancer-related mortality, and triple-negative breast cancer (TNBC) is a particularly aggressive subtype associated with high mortality rates, especially among younger females. TNBC poses a considerable clinical challenge due to its aggressive tumor behavior and limited therapeutic options. Aberrations within the PI3K/AKT pathway are prevalent in TNBC and correlate with increased therapeutic intervention resistance and poor outcomes. MicroRNAs (miRs) have emerged as crucial PI3K/AKT pathway regulators influencing various cellular processes involved in TNBC pathogenesis. The levels of miRs, including miR-193, miR-4649-5p, and miR-449a, undergo notable changes in TNBC tumor tissues, emphasizing their significance in cancer biology. This review explored the intricate interplay between miR variants and PI3K/AKT signaling in TNBC. The review focused on the molecular mechanisms underlying miR-mediated dysregulation of this pathway and highlighted specific miRs and their targets. In addition, we explore the clinical implications of miR dysregulation in TNBC, particularly its correlation with TNBC prognosis and therapeutic resistance. Elucidating the roles of miRs in modulating the PI3K/AKT signaling pathway will enhance our understanding of TNBC biology and unveil potential therapeutic targets. This comprehensive review aims to discuss current knowledge and open promising avenues for future research, ultimately facilitating the development of precise and effective treatments for patients with TNBC.

Identification and experimental verification of a biomarker by combining the unfolded protein response with the immune cells in colon cancer.

The unfolded protein response (UPR) is associated with immune cells that regulate the biological behavior of tumors. This article aims to combine UPR-associated genes with immune cells to find a prognostic marker and to verify its connection to the UPR. Univariate cox analysis was used to screen prognostically relevant UPRs and further screened for key UPRs among them by machine learning. ssGSEA was used to calculate immune cell abundance. Univariate cox analysis was used to screen for prognostically relevant immune cells. Multivariate cox analysis was used to calculate UPR_score and Tumor Immune Microenvironment score (TIME_score). WGCNA was used to screen UPR-Immune-related (UI-related) genes. Consensus clustering analysis was used to classify patients into molecular subtype. Based on the UI-related genes, we classified colon adenocarcinoma (COAD) samples by cluster analysis. Single-cell analysis was used to analyze the role of UI-related genes. We detected the function of TIMP1 by cell counting and transwell. Immunoblotting was used to detect whether TIMP1 was regulated by key UPR genes. Combined UPR-related genes and immune cells can determine the prognosis of COAD patients. Cluster analysis showed that UI-related genes were associated with clinical features of COAD. Single-cell analysis revealed that UI-related genes may act through stromal cells. We defined three key UI-related genes by machine learning algorithms. Finally, we found that TIMP1, regulated by key genes of UPR, promoted colon cancer proliferation and metastasis. We found that TIMP1 was a prognostic marker and experimentally confirmed that TIMP1 was regulated by key genes of UPR.

Circ-CDK8 regulates SLC7A11-mediated ferroptosis by inhibiting miR-615-5p to promote progression in oral squamous cell carcinomas.

Introduction: Ferroptosis is a new mode of programmed cell death distinct from necrosis, apoptosis, and autophagy, induced by iron-ion-dependent lipid peroxide accumulation. Circular RNAs are a class of endogenous non-coding RNAs that regulate the biological behavior of tumors. However, the role of circ-CDK8 in regulating ferroptosis, migration, and invasion of oral squamous cell carcinoma (OSCC) remains unknown. Methods: The effect of circ-CDK8 on OSCC cell ferroptosis, migration, and invasion was evaluated using CCK-8, wound healing, transwell, reactive oxygen species (ROS), malondialdehyde (MDA), and GSH assays and Western blotting. Bioinformatics analyses and luciferase reporter assays were performed and revealed targeted relationships between circ-CDK8 and miR-615-5p, miR-615-5p and SLC7A11. Interference with circ-CDK8 expression reduced SLC7A11 expression by sponging miR-615-5p, suppressed OSCC cell migration and invasion, and promoted ferroptosis by increasing ROS, MDA, and iron levels and decreasing GSH and GPX4 levels in OSCC cells. Furthermore, in vivo, animal experiments confirmed that circ-CDK8 interference inhibited OSCC cell proliferation and SLC7A11 expression. Results: Collectively, this study revealed a novel strategy to upregulate erastin-induced ferroptosis in OSCC cells via the circ-CDK8/miR-615-5p/SLC7A11 axis, providing new insights into OSCC and a potential therapeutic strategy for OSCC.

Applications of Multimodal Artificial Intelligence in Non-Hodgkin Lymphoma B Cells.

Given advancements in large-scale data and AI, integrating multimodal artificial intelligence into cancer research can enhance our understanding of tumor behavior by simultaneously processing diverse biomedical data types. In this review, we explore the potential of multimodal AI in comprehending B-cell non-Hodgkin lymphomas (B-NHLs). B-cell non-Hodgkin lymphomas (B-NHLs) represent a particular challenge in oncology due to tumor heterogeneity and the intricate ecosystem in which tumors develop. These complexities complicate diagnosis, prognosis, and therapy response, emphasizing the need to use sophisticated approaches to enhance personalized treatment strategies for better patient outcomes. Therefore, multimodal AI can be leveraged to synthesize critical information from available biomedical data such as clinical record, imaging, pathology and omics data, to picture the whole tumor. In this review, we first define various types of modalities, multimodal AI frameworks, and several applications in precision medicine. Then, we provide several examples of its usage in B-NHLs, for analyzing the complexity of the ecosystem, identifying immune biomarkers, optimizing therapy strategy, and its clinical applications. Lastly, we address the limitations and future directions of multimodal AI, highlighting the need to overcome these challenges for better clinical practice and application in healthcare.

Construction and validation of a prognostic model for overall survival time of patients with ovarian cancer by metabolism-related genes.

Ovarian cancer is a female-specific malignancy with high morbidity and mortality. The metabolic reprogramming of tumor cells is closely related to the biological behavior of tumors. The prognostic signature of the metabolism-related gene (MRGs) was established by LASSO-Cox regression analysis. The prognostic signature of MRGs was also prognosticated in each clinical subgroup. These genes were subjected to functional enrichment analysis and tissue expression exploration. Analysis of the MRG prognostic signature in terms of immune cell infiltration and antitumor drug susceptibility was also performed. A MRG prognostic signature including 21 genes was established and validated. Most of the 21 MRGs were expressed at different levels in ovarian cancer than in normal ovarian tissue. The enrichment analysis suggested that MRGs were involved in lipid metabolism, membrane organization, and molecular binding. The MRG prognostic signature demonstrated the predictive value of overall survival time in various clinical subgroups. The monocyte, NKT, Tgd and Tex cell scores showed differences between the groups with high- and low-risk score. The antineoplastic drug analysis we performed provided information on ovarian cancer drug therapy and drug resistance. In vitro experiments verified that PLCH1 in 21 MRGs can regulate the apoptosis and proliferation of ovarian cancer cells. This metabolism-related prognostic signature was a potential prognostic factor in patients with ovarian cancer, demonstrating high stability and accuracy.