Clinical Tumor Research Articles

Giant benign mesenteric cysts (mesothelioma and lymphangioma): A report of two cases

Introduction and importanceMesenteric cysts are a rare group of intra-abdominal tumors located in the mesentery or omentum, most of this lesion are asymptomatically but occasionally presents with non-specific symptoms, which makes diagnosis difficult. Case presentationWe present two cases of giant mesenteric cyst in our Institution, the first case is a women of 23 years with previous gynecologic surgery with chronic abdominal pain and large abdominal mass CT showed a giant intraabdominal 30 × 25 × 15 cm, the patient went to laparotomy and a large mesenteric tumor found. The Histopathology reported a Benign cyst mesothelioma (BCM). The second case is a 47 year male with intermittent abdominal pain and abdominal CT shows a 20x21x15 cm tumor. Laparotomy was performed. Histopathology reported a large lymphangioma. Clinical discussionBCM tumors are rare intrabdominal lesions often diagnosed in premenopausal women. Its etiopathogenesis is still unclear, associated risk factors are endometriosis, pelvic inflammatory disease and previous pelvic surgery. Lymphangiomas are an infrequent cyst tumors. It results from a failure in the evolutionary development of the lymphatic system, often localized in the head and neck and its localization in the abdomen is even rare. The definitive diagnosis is made by histopathology. ConclusionMesenteric cysts diagnosis if often challenge due to nonspecific symptoms and significant overlap in imaging appearance between the different entities, its diagnosis should be in mind when encounter a cystic abdominal tumor, surgical complete removal of this tumors is the optimal treatment to prevent recurrence and complications.

Artificial Intelligence Application for Anti-tumor Drug Synergy Prediction.

Currently, the main therapeutic methods for cancer include surgery, radiation therapy, and chemotherapy. However, chemotherapy still plays an important role in tumor therapy. Due to the variety of pathogenic factors, the development process of tumors is complex and regulated by many factors, and the treatment of a single drug is easy to cause the human body to produce a drug-resistant phenotype to specific drugs and eventually leads to treatment failure. In the process of clinical tumor treatment, the combination of multiple drugs can produce stronger anti-tumor effects by regulating multiple mechanisms and can reduce the problem of tumor drug resistance while reducing the toxic side effects of drugs. Therefore, it is still a great challenge to construct an efficient and accurate screening method that can systematically consider the synergistic anti- tumor effects of multiple drugs. However, anti-tumor drug synergy prediction is of importance in improving cancer treatment outcomes. However, identifying effective drug combinations remains a complex and challenging task. This review provides a comprehensive overview of cancer drug synergy therapy and the application of artificial intelligence (AI) techniques in cancer drug synergy prediction. In addition, we discuss the challenges and perspectives associated with deep learning approaches. In conclusion, the review of the AI techniques' application in cancer drug synergy prediction can further advance our understanding of cancer drug synergy and provide more effective treatment plans and reasonable drug use strategies for clinical guidance.

Unlocking the diagnostic potential of vascular endothelial growth factor and interleukin-17: Advancing early detection strategies for hepatocellular carcinoma

Tian et al investigated the diagnostic value of serum vascular endothelial growth factor (VEGF) and interleukin-17 (IL-17) in primary hepatocellular carcinoma (PHC). Their retrospective study, published in the World Journal of Gastrointestinal Surgery , revealed that the serum levels of VEGF and IL-17 are significantly elevated in PHC patients compared with healthy controls. These biomarkers are closely associated with pathological features such as tumor metastasis and clinical tumor node metastasis stage. A receiver operating characteristic analysis further confirmed the diagnostic efficacy thereof, suggesting that VEGF and IL-17 could serve as valuable tools for early detection and treatment guidance. This study underscores the potential of integrating these biomarkers into clinical practice to increase diagnostic accuracy and improve patient management in PHC.

Analysis of positive predictors in diagnosing lung cancer on transthoracic and transbronchial procedure

Background: Lung cancer remains the most cause of death due to cancer. Due to high mortality rate of lung cancer, early diagnosis of lung cancer plays a very important role in therapeutic management. Clinical symptoms and tumor characteristics such as size and location are found to vary in lung cancer patients. Various modalities can be used to obtain materials or samples include transthoracic and transbronchial methods. Research was conducted to analyze positive predictors of cancer between transthoracic and transbronchial procedures in lung cancer patients. Methods: This research is an analytical observational study with a cross-sectional design in using secondary data through medical records from January 2022 to December 2023. Univariate analysis presents data in the form of frequency, mean and standard deviation. Bivariate analysis was carried out using chi-square and multivariate analysis using multiple logistic regression. The measure used as a predictor is the adjusted odds ratio. Inference or conclusion is based on the 95% confident interval and p value at the alpha value limit of 0.05. The entire data process above uses SPSS 26.0 statistical software Results: The total research subjects who met the research requirements were 111 patients. The characteristics of the research subjects were symptoms of cough (n=97; 87.4%), hemoptyisis (n=51; 45.9%), breathlessness (n=104; 93.7%) and chest pain (n=87; 78.4%), mostly peripheral tumor (n=70; 63.1%) and size >3 cm (n=103; 92.8%). Logistic regression analysis showed cough symptoms and peripheral tumor location each had an adjOR value of 5.247 (95% CI 1.432-19.552; p=0.013) and adjOR 0.088 (95% CI 0.034-0.229; p=0.000) for lung cancer positivity on transbronchial procedure. On transthoracic procedure, cough symptoms and peripheral tumor location respectively had an adjOR value of 0.190 (95% CI 0.051-0.703; p=0.013) and adjOR 11.407 (95% CI 4.374-29.747; p=0.000) for lung cancer positivity. Conclusions: Cough is a positive predictor of lung cancer in transbronchial procedures. Meanwhile, peripheral tumor location is a positive predictor of lung cancer in transthoracic procedures.

Abstract B017: Discovery of cancer-specific small RNAs using a new unbiased analysis of cohort sequence data

Abstract It is well-established that small RNAs such as microRNAs can have important roles as oncogenes or tumor suppressors. The majority of studies of small RNAs in cancer have focused on examining the often subtle deregulation of specific, well-characterized molecules, aiming to understand their role in tumorigenesis. However, these efforts have predominantly concentrated on known, well-annotated RNA sequences, potentially overlooking novel, cancer-specific molecules. In this study, we sought to apply a new computational approach to uncover small RNA molecules that are uniquely associated with cancer and are completely absent from all non- cancerous tissues. To achieve this, we developed an unbiased approach that can detect cancer- specific sequences even if they are lowly abundant, do not overlap with existing genome annotations and even if they do not map to the human reference genome. We applied our framework to hundreds of small RNA-seq samples across a diverse range of cancer types from two large-scale public resources: The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Through this comprehensive analysis, we identified a series of small RNA molecules that are exclusively present in tumor samples and completely absent in adjacent normal tissues across multiple cancer types. Furthermore, these molecules were not detected in a large cohort comprising over 2,500 non-cancerous public samples, underscoring their specificity to cancerous conditions. Some of these molecules are also associated with different patient metadata. For example, one of these candidates exhibited significant correlation with poor patient survival in both Lung Adenocarcinoma and Endometrial Carcinoma within both the TCGA and CPTAC datasets. The discovery of such cancer-specific small RNAs holds immense potential for clinical applications. These molecules could serve as highly specific diagnostic and prognostic biomarkers, aiding in the early detection and stratification of cancers. Moreover, their unique presence in cancer cells, positions them as promising targets for the development of novel therapeutic interventions. In summary, our findings highlight the importance of exploring the full spectrum of small RNAs in cancer research. By moving beyond the constraints of known annotations, we have uncovered previously unknown molecules that could improve cancer diagnostics, prognostics, and treatment. Citation Format: Panagiotis Kalogeropoulos, Maria Alejandra Ulloa, Marc Friedländer. Discovery of cancer-specific small RNAs using a new unbiased analysis of cohort sequence data [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr B017.

Enhancing pancreatic tumor delineation using dual-energy CT-derived extracellular volume fraction map.

Precise identification of pancreatic tumors is challenging for radiotherapy planning due to the anatomical variability of the tumor and poor visualization of the tumor on 3D cross-sectional imaging. Low extracellular volume fraction (ECVf) correlates with poor vasculature uptake and possible necrosis or hypoxia in pancreatic tumors. This work investigates the feasibility of delineating pancreatic tumors using ECVf spatial distribution maps derived from contrast enhanced dual-energy CT (DECT). Data acquired from radiotherapy simulation of 12 pancreatic cancer patients, using a dual source DECT scanner, were analyzed. For each patient, an ECVf distribution of the pancreas was computed from the simultaneously acquired low and high energy DECT series during the late arterial contrast phase combined with the patient's hematocrit level. Volume of interest (VECVf) maps in ECVf distribution of pancreas were identified by applying an appropriate threshold condition and a connected components clustering algorithm. The obtained VECVf was compared with the clinical gross tumor volume (GTV) using the positive predictive value (PPV), Dice similarity coefficient (DSC), mean distance to agreement (MDA) and true positive rate (TPR). As a proof of concept, our hypothetical threshold condition based on the first quartile separation of the ECVf distribution to find VECVf of the pancreas elucidates the tumor volume within the pancreas. Notably, 7 out of 12 cases studied for VECVf matched well with the GTV and the mean PPV of 0.83±0.12. The mean MDA (2.83±1.0) of the cases confirms that VECVf lies within the tolerance for comparing to the pancreatic GTV. For the remaining 5 cases, the VECVf is substantially affected by other compounding factors, e.g., large cysts, dilate ducts, and thus did not align with the GTVs. This work demonstrated the promising application of the ECVf map, derived from contrast enhanced DECT, to help delineate tumor target for RT planning of pancreatic cancer.

FXR deficiency induced ferroptosis via modulation of the CBP-dependent p53 acetylation to suppress breast cancer growth and metastasis.

Farnesoid X receptor (NR1H4/FXR) functions as a scavenger of lipid peroxide products and drives the proliferation and metastasis of various cancers. However, the underlying molecular mechanisms remain poorly understood. In our study, we found that the expression levels of FXR, vimentin and SLC7A11 were significantly higher in breast cancer tissues, particularly in metastatic cancer tissues compared to non-metastatic ones. Furthermore, the increased FXR expression was positively correlated with vimentin and SLC7A11 in clinical tumor specimens. In addition, a high level of FXR correlated with poor prognosis in patients with breast cancer. Both Z-Guggulsterone (Z-GS), as a pharmacological inhibitor of FXR, and silencing FXR curbed proliferation and migration of breast cancer cells by promoting ferroptosis. Notably, our results showed that FXR competitively bound to CREB-binding protein (CBP) to suppress the interaction between p53 and CBP in the nucleus, and thus prevented p53 acetylation at lys382, which was essential for upregulating the expression of SLC7A11. Conversely, FXR knockdown increased the interaction between p53 and CBP and promoted p53 acetylation, which ultimately led to facilitating ferroptosis in breast cancer cells. More importantly, we also found that Z-GS inhibited TGF-β1-induced tumor growth and metastasis of breast cancer primarily through ferroptosis via regulating CBP-dependent p53 acetylation in nude mice. In conclusion, the FXR was first reported as a tumor promoter that enhanced the proliferation and metastasis of breast cancer cells through regulating CBP-dependent p53 K382 acetylation. It proposes that FXR may serve as a potential therapeutic target for the treatment of breast cancer.

Exosomal integrins in tumor progression, treatment and clinical prediction (Review).

Integrins are a large family of cell adhesion molecules involved in tumor cell differentiation, migration, proliferation and neovascularization. Tumor cell‑derived exosomes carry a large number of integrins, which are closely associated with tumor progression. As crucial mediators of intercellular communication, exosomal integrins have gained attention in the field of cancer biology. The present review examined the regulatory mechanisms of exosomal integrins in tumor cell proliferation, migration and invasion, and emphasized their notable roles in tumor initiation and progression. The potential of exosomal integrins as drug delivery systems in cancer treatment was explored. Additionally, the potential of exosomal integrins in clinical tumor prediction was considered, while summarizing their applications in diagnosis, prognosis assessment and treatment response prediction. Thus, the present review aimed to provide guidance and insights for future basic research and the clinical translation of exosomal integrins. The study of exosomal integrins is poised to offer new perspectives and methods for precise cancer treatment and clinical prediction.

Lactylation Modification as a Promoter of Bladder Cancer: Insights from Multi-Omics Analysis

Bladder cancer (BLAC) is a malignant tumor with high morbidity and mortality. The establishment of a prognostic model for BLAC is of great significance for clinical prognosis prediction and treatment guidance. Lactylation modification is a newly discovered post-transcriptional modification of proteins, which is closely related to the occurrence and development of tumors. Multiple omics data of BLAC were obtained from the GEO database and TCGA database. The Lasso algorithm was used to establish a prognostic model related to lactylation modification, and its predictive ability was tested with a validation cohort. Functional enrichment analysis, tumor microenvironment analysis, and treatment response evaluation were performed on the high- and low-risk groups. Single-cell and spatial transcriptome data were used to analyze the distribution characteristics of model genes and their changes during epithelial carcinogenesis. A prognostic model consisting of 12 genes was constructed. The survival rate of the high-risk group was significantly lower than that of the low-risk group. The multiple ROC curve showed that the prediction efficiency of the model was higher than that of the traditional clinical tumor grading. Functional enrichment analysis showed that glycolysis and hypoxia pathways were significantly upregulated in the high-risk group. The high-risk group was more sensitive to most first-line chemotherapy drugs, while the low-risk group had a better response to immunotherapy. Single-cell sequencing analysis revealed the dynamic changes of model genes during the transition of epithelial cells to squamous-differentiated cells. Spatial transcriptome analysis showed the spatial distribution characteristics of the model genes. The lactylation-related models have a satisfactory predictive ability and the potential to guide the clinical treatment of BLAC. This model has significant biological implications at the single-cell level as well as at the spatial level.

EXTH-28. DEVELOPING A NOVEL INJECTABLE IMMUNOTHERAPEUTIC GEL FOR ENCAPSULATION OF NATURAL KILLER CELLS FOR POST-SURGICAL GLIOBLASTOMA TREATMENT

Abstract Malignant brain tumors are one of the leading causes of death among all cancers. Approximately 40,000 people are diagnosed with malignant brain tumors every year. Among these patients, 15,000 cases are glioblastoma (GBM) with a very poor prognosis; even after aggressive surgical resection and adjuvant chemo/radiotherapy, the median survival is only 14.6 months. The major reason for poor prognosis is the blood-brain barrier, which prevents therapeutic agents from reaching the target area. Therefore, there are only a few choices of drugs available for brain tumor treatment. To date, temozolomide (TMZ) and the Gliadel wafer have been clinically used as standard chemotherapy agents after brain tumor resection. However, drug resistance to TMZ and the poor drug diffusion rate of the Gliadel wafer still result in ineffective suppression of residual cancer cells. To overcome the above-mentioned difficulties in clinical brain tumor treatment, in situ self-crosslinking multifunctional hydrogels was developed to carry natural killer cells (NK cells) and radiosensitizers as a novel brain tumor treatment system. Unlike traditional hydrogels catalyzed by pH value or temperature, this new system is stable and consistent as an immune cell carrier. We used fibrinogen, thrombin, and alginic acid as the backbone of the in situ self-crosslinking hydrogel, tested the properties of the synthesized hydrogel, and analyzed the gel-formation time and swelling rate. The release rate of NK cells was also examined. In a brain tumor animal model, the use of hydrogel-NK cells significantly inhibited tumor proliferation and prolonged animal survival time. In conclusion, this therapeutic hydrogel carrying NK cells can serve as a novel post-operation adjuvant therapeutic tool for malignant brain tumors.

Inter-center comparison of proton range verification prototypes with an anthropomorphic head phantom**F. Hueso-González and J. Berthold share first authorship. J. Verburg and C. Richter share last authorship. P. Wohlfahrt was essential for the work conception, treatment planning design and equalization, and for the transatlantic transport of the phantom.

Objective. To compare in reproducible and equalized conditions the performance of two independent proton range verification systems based on prompt gamma-ray detectors from two different proton therapy centers.Approach. An anthropomorphic head phantom with calibrated stopping power, serving as ground truth, was irradiated with comparable treatment plans, spot positions and energies in both facilities. Clinical beam current, tumor contour and dose were used. The absolute range measurement was compared to the expected value according to the ground truth. The statistical precision was assessed by repeating each measurement ten times. Sensitivity to relative range shifts was evaluated by introducing 2 mm and 5 mm plastic slabs on half of the field.Main results. The resulting absolute range accuracy was within 2.4 mm in all cases. Relative range shifts were detected with deviations lower than 14%.Significance. The performance of both systems was deemed worthy of clinical application for the detection of range deviations. This study represents the first comparison of independent prompt gamma-ray-based proton range verification systems under equalized conditions with realistic treatment fields and beam currents.

INNV-12. CUTANEOUS TOXICITIES OF MITOGEN-ACTIVATED PROTEIN KINASE INHIBITORS IN CHILDREN AND YOUNG ADULTS WITH NEUROFIBROMATOSIS-1

Abstract BACKGROUND Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder which commonly causes neoplasms leading to disfigurement or dysfunction. Mitogen-activated protein kinase inhibitors (MEKi) are generally well-tolerated treatments which target neural tumor progression in patients with NF1. Cutaneous adverse events (CAEs) are common and may hinder patients’ abilities to remain on treatment, particularly in children. We aim to characterize CAEs secondary to MEKi treatment in pediatric and young adult patients with NF1. METHODS We reviewed institutional medical records of patients under 30 years with a diagnosis of “NF1,” “NF2,” or “other neurofibromatoses” on MEKi therapy between January 1, 2019 and June 1, 2022. We recorded the time-to-onset, type, and distribution of CAEs, non-cutaneous adverse events (AEs), AE management, and tumor response. RESULTS The median age of 40 patients with NF1 was 14 years old. Tumor types included low-grade gliomas (51%) and plexiform neurofibromas (38%). MEKi used included selumetinib (69%), trametinib (25%), and mirdametinib (6%) (Table 1). A total of 74 CAEs occurred, with 28 cases of acneiform rash (38%) (Figure 1). Twenty-three out of the 28 cases of acneiform eruption were in post-pubertal patients (82.1%). Other common CAEs were paronychia, seborrheic dermatitis, eczema, xerosis, and oral mucositis. The most common treatments included oral antibiotics and topical corticosteroids. Most patients had clinical (stable or improved) tumor response (71%) while 29% had tumor progression while on a MEKi (Table 2). There was no significant association between CAE presence and tumor response (p=0.39). CONCLUSIONS MEK inhibitors have been demonstrated as a valuable treatment, but CAEs complicate the ability to stay on the treatment. Most patients in our cohort developed a CAE, demonstrating its prevalence in this population. Improvement in characterization of MEKi toxicities and their management is important to develop treatment guidelines for pediatric and young adult patients with NF1 on MEKi therapy.

RNF4 mediated degradation of PDHA1 promotes colorectal cancer metabolism and metastasis

This study investigates the role of RNF4-mediated ubiquitination and degradation of PDHA1 in colorectal cancer (CRC) metabolism and metastasis. Integrating (The Cancer Genome Atlas) TCGA and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, proteomic, clinical, and metabolomic analyses were performed, revealing PDHA1 as a prognostic marker in CRC. Immunohistochemical staining confirmed lower PDHA1 expression in metastatic CRC tissues. In vitro experiments demonstrated that PDHA1 overexpression inhibited CRC cell proliferation, migration, and invasion. RNF4 was identified as a key mediator in the ubiquitination degradation of PDHA1, influencing glycolytic pathways in CRC cells. Metabolomic analysis of serum samples from metastatic CRC patients further supported these findings. In vivo experiments, including xenograft and metastasis models, validated that RNF4 knockdown stabilized PDHA1, inhibiting tumor formation and metastasis. This study highlights the critical role of RNF4-mediated PDHA1 ubiquitination in promoting glycolytic metabolism, proliferation, and metastasis in CRC.

Surgical Management of Symptomatic Recurrent/Progressive Craniopharyngioma: Is There a Gold-Standard Approach?

The standard treatment for craniopharyngiomas (CPs) involves either initial gross total resection or subtotal resection with adjuvant radiotherapy. However, there is no consensus regarding the management of recurrent cases. We reviewed a series of patients with CP to evaluate the characteristics of patients with recurrent/progressing CP. We retrospectively reviewed 31 patients with biopsy-proven recurrent/progressed CP who were initially operated on at our clinic from 2015 to 2023. Demographic and clinical data, including age, sex, tumor localization, lesion size and features, radiological findings, and endocrine, neurologic, and ophthalmological issues, were compared between those with and without recurrence. Fifteen out of 31 patients (48.4%) underwent transnasal/transsphenoidal endoscopic surgery; the remaining 16 underwent microscopic transcranial or neuroendoscopic surgery. After treatment, recurrence and events (any medical condition related to the patient's current condition other than recurrence) were observed in 48.4% and 32.3% of the cases, respectively. There were no statistically significant disparities between patients with and without recurrence in terms of age, tumor dimensions, tumor localization, gender distribution, surgical modality, or the presence of calcifications or hydrocephalus (p > 0.05). The highest and lowest overall survival was 25 years and 6 months, respectively. The management of recurrent CP is too complicated to fit into a standard treatment algorithm. Therefore, surgical treatment for these patients should be individualized and planned according to patient symptoms and radiological findings, which is presumably a more versatile, efficient, and safe approach for recurrent CPs.

Unveiling the distinctive variations in multi-omics triggered by TP53 mutation in lung cancer subtypes: An insight from interaction among intratumoral microbiota, tumor microenvironment, and pathology

The TP53 mutation is one of the most common gene mutations in non-small cell lung cancer (NSCLC) and plays a significant role in the occurrence, development, and prognosis of both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Recent studies have also suggested the predictive value of TP53 mutations in the response to immunotherapy for NSCLC. It is known that intratumoral microbiota, tumor immune microenvironment (TIME) and histology are associated with the roles of TP53 mutation in NSCLC. However, the intrinsic associations among these three factors and their underlying interaction with TP53 mutation are not well understood. Additionally, the potential of predicting TP53 mutations using deep learning methods has not yet been fully evaluated. In this paper, we comprehensively evaluated the tissue microbiome, host gene expression characteristics, and histopathological slides of 992 NSCLC patients obtained from the cancer genome atlas (TCGA) and validated the findings using multi-omics data of 332 NSCLC patients from the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Compared to LUSC, LUAD exhibited more substantial differences between patients with and without TP53 mutation in all three aspects. In LUAD, our results imply underlying links between the tissue microbiome and immune cell components in the TIME, and show that the abundance of immune cells is reflected in histology slides. Furthermore, we propose a novel multimodal deep learning model that focuses on histopathology images, which achieves an area under the curve (AUC) of 0.84 in LUAD. In summary, TP53 mutation of LUAD resulted more significant changes in intratumoral microbiota, TIME and histology than that of LUSC. And histopathology images can be used to predict TP53 mutation in LUAD with reasonable accuracy.

A pan-cancer study of ADAM9’s immunological function and prognostic value particularly in liver cancer

A pan-cancer analysis summarizing the overall changes in mRNA and protein stability of ADM9, as well as its oncogenic function on immune cell line modulation and checkpoints within the tumor microenvironment (TME), is lacking, despite the fact that ADM9 up-regulation is correlated with the progression of many cancers. Therefore, in this study, we comprehensively analyzed the role of ADAM9 expression and its prognostic value in different cancers to fill this gap. Multiple bioinformatics databases such as Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) were used to evaluate the ADAM9 genetic alternation, phosphorylation, and methylation, and indicated highly positive correlated genes that might play a critical interaction with ADAM9 and their molecular function with GO analysis. We also evaluate the effect of higher ADAM9 with prominent immune modulatory genes and immune infiltration especially in liver cancer pathogenesis stimulates lower NK cell effector functions based on its role in MICA shedding and increasing the Tregs infiltration. Immunohistochemistry (IHC) staining from 90 pathologically verified samples proved the positive correlation between ADAM9 and tumor stages and proved the higher expression of ADAM9 correlated genes (SNX9, APP, TNF, CDH1, ITGAV, MAD2L2) in HCC pathogenesis. In conclusion, this pan-cancer study provides a comprehensive understanding of the prognostic value of ADAM9 in various tumors emphasizing its importance to be considered as an innovative treatment approach, especially in tumor immunity shortly.

Spotlight on Mitochondrial Health: A Trailblazing Fluorescent Tool for Cancer Detection and Surgical Guidance.

Mitochondria play a pivotal role in maintaining normal physiological functions. Mitochondrial autophagy, namely, mitophagy, is a selective catabolic disposal of impaired mitochondria through an autophagic mechanism during episodes of mitochondrial harm. This selective removal, e.g., mitophagy, is essential for mitochondrial quality control and is closely related to the pathogenesis of many diseases. The abnormal buildup of defective mitochondria in vivo was used as a target to prevent the development of cancer. The mitochondrial autophagy process of disease-related cells is usually accompanied by a decrease in polarity and pH, and the fluorescence sensing effects caused by these two factors are usually contradictory. Here, we propose a reinventing strategy to develop a dual-channel and dual-responsive fluorescent probe HDTVB that is capable of tracking mitochondrial autophagy by monitoring fluctuations in mitochondrial pH and polarity. Based on the aggregation-induced emission (AIE) moiety and hemicarpine moiety push-pull system with activated near-infrared (NIR) emission and pH-activatable cyclization reaction, HDTVB was able to differentiate tumors from normal sites via polarity- and acidity-triggered structural changes of the probe in the course of mitochondrial autophagy. HDTVB is expected to be applied to clinical diagnosis and tumor excision guided by fluorescence, offering a new route in physiological and biochemical research.

Engineered nanoplatform mediated gas therapy enhanced ferroptosis for tumor therapy in vivo

The high glutathione (GSH) environment poses a significant challenge for inducing ferroptosis in tumor cells, necessitating the development of nanoplatforms that can deplete intracellular GSH. In this study, we developed an engineered nanoplatform (MIL-100@Era/L-Arg-HA) that enhances ferroptosis through gas therapy. First, we confirmed that the Fe element in the nanoplatform undergoes valence changes under the influence of high GSH and H2O2 in tumor cells. Meanwhile, L-Arg generates NO gas in the presence of intracellular H2O2, which reacts with GSH. Additionally, Erastin depletes GSH by inhibiting the cystine/glutamate antiporter system, reducing cystine uptake and impairing GPX4, while also increasing intracellular H2O2 levels by activating NOX4 protein expression. Through these combined GSH-depletion mechanisms, we demonstrated that MIL-100@Era/L-Arg-HA effectively depletes GSH levels, disrupts GPX4 function, and increases intracellular lipid ROS levels in vitro. Furthermore, this nanoplatform significantly inhibited tumor cell growth and extended the survival time of tumor-bearing mice in vivo. This engineered nanoplatform, which enhances ferroptosis through gas therapy, shows significant promise for ferroptosis-based cancer therapy and offers potential strategies for clinical tumor treatment.

Ten Hypermethylated lncRNA Genes Are Specifically Involved in the Initiation, Progression, and Lymphatic and Peritoneal Metastasis of Epithelial Ovarian Cancer.

Our work aimed to evaluate and differentiate the role of ten lncRNA genes (GAS5, HAND2-AS1, KCNK15-AS1, MAGI2-AS3, MEG3, SEMA3B-AS1, SNHG6, SSTR5-AS1, ZEB1-AS1, and ZNF667-AS1) in the development and progression of epithelial ovarian cancer (EOC). A representative set of clinical samples was used: 140 primary tumors from patients without and with metastases and 59 peritoneal metastases. Using MS-qPCR, we demonstrated an increase in methylation levels of all ten lncRNA genes in tumors compared to normal tissues (p < 0.001). Using RT-qPCR, we showed downregulation and an inverse relationship between methylation and expression levels for ten lncRNAs (rs < -0.5). We further identified lncRNA genes that were specifically hypermethylated in tumors from patients with metastases to lymph nodes (HAND2-AS1), peritoneum (KCNK15-AS1, MEG3, and SEMA3B-AS1), and greater omentum (MEG3, SEMA3B-AS1, and ZNF667-AS1). The same four lncRNA genes involved in peritoneal spread were associated with clinical stage and tumor extent (p < 0.001). Interestingly, we found a reversion from increase to decrease in the hypermethylation level of five metastasis-related lncRNA genes (MEG3, SEMA3B-AS1, SSTR5-AS1, ZEB1-AS1, and ZNF667-AS1) in 59 peritoneal metastases. This reversion may be associated with partial epithelial-mesenchymal transition (EMT) in metastatic cells, as indicated by a decrease in the level of the EMT marker, CDH1 mRNA (p < 0.01). Furthermore, novel mRNA targets and regulated miRNAs were predicted for a number of the studied lncRNAs using the NCBI GEO datasets and analyzed by RT-qPCR and transfection of SKOV3 and OVCAR3 cells. In addition, hypermethylation of SEMA3B-AS1, SSTR5-AS1, and ZNF667-AS1 genes was proposed as a marker for overall survival in patients with EOC.

Significant Effect of Carbon-Ion Radiation Therapy Combined With Androgen Deprivation on Biochemical Recurrence Rates in High-Risk Prostate Cancer Patients: A Two-Center Controlled Trial Compare With X-Ray External Beam Radiation Therapy.

To compare the effects of carbon-ion radiation therapy (CIRT) and external beam radiotherapy (EBRT) on the prognosis of patients with prostate cancer. The effects of initial prostate-specific antigen (iPSA), clinical Tumor (cT) stage, radiotherapy method, and other clinical factors on the prognosis of 577 patients with radiotherapy were analyzed. Cox regression analysis showed that CIRT (RR: 0.49, p = 0.0215), cT stage ≥ 3 (RR: 2.72, p = 0.0003), and iPSA ≥ 16 ng/mL (RR: 1.74, p = 0.0347) were independent predictors of biochemical recurrence (BCR). After propensity score matching (PSM), CIRT (RR: 0.42, p = 0.0147), cT stage ≥ 3 (RR: 2.55, p = 0.0092), and iPSA ≥ 16 ng/mL (RR: 2.12, p = 0.0366) were still the predictors of univariate analysis. In multivariate analysis, CIRT (RR: 0.42, p = 0.015) and cT stage≥ 3 (RR:2.21, p = 0.0332) were independent predictors of BCR. Among them, we used iPSA and cT stages to establish a new radiotherapy selection model based on BCR risk. Patients who met more than one factor (score ≥ 1) and underwent CIRT had significantly better BCR progression-free survival (PFS) than those who received EBRT (p ≤ 0.01). This was also confirmed by Kaplan-Meier analysis after PSM. CIRT patients exhibited lower 5-year BCR rates compared to the EBRT group. Patients with a risk score of our model ≥ 1 undergoing CIRT were more likely to experience BCR benefits compared to those receiving EBRT.