Tumor-related Death Research Articles

Low Phosphatidylserine+ Cells Within the CD34+/CD45dim/CD117(c-kit)+ Subpopulation are Associated with Poor Outcomes in Metastatic Colorectal Cancer

Background: Colorectal cancer is among the most prevalent causes of tumor-related deaths worldwide. Antiangiogenic therapy represents a cornerstone of metastatic CRC treatment, and biomarkers are advocated for the optimization of this therapeutic strategy. Methods: In this observational prospective study, we employed an optimized flow cytometry protocol to investigate the prognostic and predictive potential of blood circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPCs), and related subsets in a cohort of patients with metastatic colorectal cancer (n = 40). Results: Computational FC analysis revealed a differential enrichment of blood cell clusters with a CD34+/CD45dim/CD117(c-kit)+ phenotype between responders and non-responders both to antiangiogenic and non-antiangiogenic treatments. Intriguingly, our results show that a high percentage of annexin V-negative cells in a putative circulating progenitor population with a CD34+/CD45dim/CD117+ phenotype was correlated with a reduced response to systemic anticancer treatments (p = 0.015) and worse overall survival (log-rank p = 0.03). In addition, we observed increased blood concentrations of CD34+/CD45dim/CD117+/annexin V- cells in patients with a higher number of metastatic sites (p = 0.03). Conclusions: Overall, these findings hold promise for the identification of novel circulating biomarkers to develop more personalized treatment approaches in patients with metastatic colorectal cancer.

Prospect of (Nd3+) Complexes and Its Nanoparticles as Promising Novel Anticancer Agents in Particular Targeting Breast Cancer Cell Lines

Breast cancer is the leading cause of tumor-related death in women around much of the world and a major health burden for modern medicine. This review highlights the prospect of (Nd3+) complexes and nanoparticles as promising novel anticancer agents in particular targeting breast cancer cell lines. This study emphasizes the therapeutic and diagnostic potentials of Nd3+-based metal complexes, especially in reversing drug resistance or enhancing targeted therapy. A comprehensive overview of diagnostic modalities underscores the imperative for the prompt identification and intervention of breast cancer. Nd3+ complexes demonstrate potential as anticancer therapeutics due to their significant cytotoxicity evidenced by their IC50 values. The research outcomes indicated that it could theoretically inhibit the growth and metastasis of cancer cell lines. Future research should focus on synthesizing novel Nd3+ complexes with enhanced bioavailability, solubility, and reduced toxicity to further advance their application.

Potentially toxic trace elemental levels in the malignant and non-malignant tissues of lungs: a comparative study by multivariate analysis from Pakistan

ABSTRACT Lung cancer is the most prevalent and main cause of tumour-related deaths across the world. Exposure to environmental and occupational toxicants such as toxic trace elements is an important cause of lung carcinoma. Keeping in view, the current investigation was aimed to measure the concentrations of 10 elements Mn, Mg, Ni, Zn, Se, Cr, Cd, Fe, Pb and Cu in the malignant tissues and non-malignant tissues samples of lungs of patients. The samples were digested in HNO3 and HClO4 solutions and analysed by using atomic absorption spectrophotometric technique. On the average, significantly elevated levels of copper , lead , cadmium and chromium were detected in the malignant tissues than the non-malignant tissues of patients. Most of the elements exhibited noticeably disparities in their concentrations based on sex, nutritional habits, habitat and smoking habits of donor groups. The correlation coefficients between the elements in malignant tissues and non-malignant tissues were significantly diversed. Based on lung cancer types, zinc and cadmium were raised in adenocarcinoma, whereas copper and cadmium were elevated in squamous cell carcinoma patients. Average magnesium, zinc and lead were highest in stage IV, while nickel and iron were maximum in stage-III of the malignant tissues. The chromium and manganese referred to be maximum at stage-II while selenium, copper and cadmium were elevated at stage-I. Multivariate statistical methods based on the elemental concentrations exhibited clearly divergent groupings which may be linked to alter the metabolism of the metals in the tumour tissues and non tumour tissues of lungs.

Prognostic value of immunosuppression scores in patients with esophageal squamous cell carcinoma: a multicenter study.

The prognostic impact of human leukocyte antigen-E (HLA-E) expression and the proportion of natural killer (NK) cells in esophageal squamous cell carcinoma (ESCC) was investigated. This study retrospectively evaluated 397 ESCC patients across two centers. The cumulative incidence of recurrence (CIR) and the incidence of tumor-related death (CID) were analyzed in various groups. An immunosuppression score (ISS) was developed based on HLA-E expression and NK cell proportion. Differences between groups were adjusted using inverse probability treatment weighting (IPTW). The factors influencing cancer-specific survival (CSS) and recurrence-free survival (RFS) were also examined. Patients with low HLA-E expression had significantly higher five-year CIR and CID compared to those with high expression (CIR: 20.7% vs. 45.1%, CID: 19.3% vs. 40.1%; p< 0.001). Similarly, NK cell-positive patients had significantly better five-year CIR and CID than NK cell-negative patients (CIR: 16.3% vs. 59.6%, CID: 13.9% vs. 53.7%; p < 0.001). The Sankey diagram indicated that the low ISS group had a lower recurrence and tumor-related mortality rate (p < 0.05). After IPTW adjustment, the low ISS group showed improved five-year RFS (80.1% vs. 35.4%, p < 0.001) and five-year CSS (82.3% vs. 42.5%, p < 0.001) compared to the high ISS group. ESCC with different ISS statuses represents two distinct biological subtypes, underscoring the need for personalized treatment strategies tailored to varying tumor behaviors.

Synergistic Therapy of Metastatic Breast Cancers by Biomimetic Chemotherapeutic Drug-Gene Nanoparticles.

Cancer metastasis is responsible for more than 90% of tumor-related deaths. Especially, metastatic breast cancer (MBC) is a common malignancy with a high mortality among women worldwide. It is urgent to develop effective drugs for the treatment of MBC. Herein, biomimetic chemotherapeutic drug-gene nanoparticles (named TPT-ASOVEGF@MM NPs) were constructed for the combination therapy of MBC. First, topotecan hydrochloride (TPT) and vascular endothelial growth factor antisense oligonucleotide (ASOVEGF) were coself-assembled in water through electrostatic interaction to produce chemotherapeutic drug-gene nanoparticles (TPT-ASOVEGF NPs). Then, the nanoparticles were encapsulated within macrophage membranes (MM) to form biomimetic TPT-ASOVEGF@MM NPs with long circulation time in blood and active tumor-targeting ability. TPT-ASOVEGF@MM NPs can be effectively internalized by breast cancer cells and then the nanoparticles collapse to simultaneously release TPT and ASOVEGF. ASOVEGF can inhibit the expression of VEGF, impeding the process of neovascularization and blocking the metastatic pathway of cancer cells. Meanwhile, TPT can bind to the topoisomerase I-DNA complex to prevent DNA repair and replication, and further induce apoptosis of cancer cells. In addition, TPT can also affect hypoxia-inducible factor 1α (HIF-1α) expression and inhibit hypoxia-induced tumor metastasis to achieve synergistic therapy with ASOVEGF. In MBC mouse models, the in vivo inhibition rate of TPT-ASOVEGF@MM NPs for lung metastasis was 89.5%, with minor toxic side effects and the least number of metastatic nodules in the lungs. In summary, TPT-ASOVEGF@MM NPs would be a promising biomimetic nanodrug for chemo-gene combination therapy of MBC with high efficacy and safety in clinics.

GEFT inhibits the GSDM-mediated proptosis signalling pathway, promoting the progression and drug resistance of rhabdomyosarcoma

The metastasis or recurrence of rhabdomyosarcoma (RMS) is the primary cause of tumour-related deaths. Patients with high-risk RMS have poor prognosis with a 5-year overall survival rate of 20–30%. The lack of specific drug-targeted therapy and chemotherapy resistance are the main reasons for treatment failure. Drugs or molecular target inhibitors can induce the pyroptosis of tumour cells or increase their sensitivity to chemotherapy, making pyroptosis an effective strategy for antitumour therapies. Pyroptosis is mediated by gasdermin (GSDM) family members. Here, we found that the expression of NLRP3, caspase-1, caspase-3, GSDMD and GSDME in RMS was remarkably lower than that in skeletal muscle tissues. Nigericin and dactinomycin in RMS cells achieved their regulatory effect on pyroptosis through the NLRP3/caspase-1/GSDMD pathway and caspase-3/GSDME pathway, respectively. Necrosulfonamide reversed the pyroptosis-related changes induced by nigericin, and siGSDME converted the dactinomycin-induced pyroptosis into apoptosis. Additionally, GEFT inhibited the GSDMD and GSDME pyroptosis pathways, thereby promoting the progression and drug resistance of RMS. Mouse xenograft and tumour analysis confirmed that nigericin and dactinomycin can effectively improve the therapeutic effect of RMS by activating the pyroptosis pathway. To the best of our knowledge, this study was the first to focus on pyroptosis in RMS. Overall, our investigation demonstrated that nigericin and dactinomycin play therapeutic roles in tumours by promoting RMS cell pyroptosis. Interference with GEFT and drug combination can exert a great inhibitory effect on tumours.

CNSC-44. TARGETING OF THE YAP/TAZ-TEAD AXIS DIMINISHES VIABILITY AND DIFFERENTIATION POTENTIAL IN PEDIATRIC HIGH-GRADE GLIOMA

Abstract Pediatric high-grade gliomas (pHGGs) are invasive and fast-growing brain malignancies. They account for up to 40% of all brain tumor-related deaths in childhood. Genetic alterations that characterize these gliomas include H3 onco-histone mutations and genetic alterations in receptor-tyrosine kinases (RTKs), including amplification, mutation, and gene fusions in RTKs. However, direct targeting with tyrosine kinase inhibitors (TKIs) has shown at best partial responses in patients due to the molecular heterogeneity within these tumors and the lack of pharmaceutical penetration into the central nervous system (CNS). Thus, alternative therapeutic approaches to treat pHGGs are urgently needed. The YAP/TAZ transcription factors, which cooperate with TEAD co-factors to promote target gene expression, orchestrate stem-cell fate decisions and proliferation downstream of growth factor signaling pathways, such as RTKs. We observed that YAP expression is upregulated in RTK mutant and H3 mutant pHGGs. Depletion of YAP via RNAi methods decreased proliferation, inhibited pHGG stem cell self-renewal, and induced apoptosis of pHGG cells. Use of Verteporfin (VP), a FDA-approved YAP/TAZ small molecule inhibitor, mimicked the effects seen by YAP genetic depletion. Using an in vitro human cortical organoid-tumor model in which tumor cells are engrafted to human brain cortical organoids, we screened for responses in tumor cells and in non-tumor cells in the neural microenvironment upon VP treatment, using single-cell RNA-sequencing and immunofluorescence to visualize responses. These organoid models offer improved models for modeling how the neural CNS microenvironment shapes responses of tumor cells to YAP/TAZ inhibition and VP treatments. Results from our work showing that YAP/TAZ-TEAD inhibition is a promising therapeutic avenue for management of pHGGs will be presented. Further pre-clinical work will follow to correlate observation and understand the therapeutic efficacy of YAP/TAZ-TEAD inhibition for pHGG treatment.

CTNI-65. DETERMINANTS OF LONG-TERM SURVIVAL IN PATIENTS WITH IDH-MUTANT GLIOMAS

Abstract BACKGROUND Survival times of patients with IDH-mutant gliomas is variable and can extend to decades. Many studies only provide progression-free rather than overall survival times and prognostic factors remain ill-defined. Here we explored clinical disease characteristics of long-term survivors within a large cohort of patients with extended follow-up. METHODS This single-center, retrospective analysis included 114 patients with IDH-mutant glioma that either died due to tumor-related causes or survived at least 15 years after first diagnosis. Patient characteristics, outcomes, and prognostic factors were stratified by short- (&amp;lt; 15 years) versus long-term (≥ 15 years) survival. Initial diagnosis was (re-)classified according to the WHO 2016 classification. Uni- and multivariate analyses were performed. RESULTS Overall, 66 patients (58%) were diagnosed with astrocytoma and 48 patients (42%) with oligodendroglioma. Median follow-up of the survivors was 16.6 years (range 15-28.9). 62 tumor-related deaths (54%) had been reported at database closure. Patients that died before reaching 15 years survival time had been diagnosed with astrocytoma in 41 (72%) and oligodendroglioma in 16 cases (28%). The long-term survivor cohort comprised 25 patients (44%) with astrocytoma and 32 patients (56%) with oligodendroglioma. Long-term survival was associated with grade 2 histology (p &amp;lt; 0.01), smaller tumor volumes (p &amp;lt; 0.01), and lack of contrast enhancement (p = 0.02). 41 long-term survivors (72%) were initially monitored by a wait-and-scan strategy as opposed to 16 patients (28%) in the cohort of short-term survival (p&amp;lt;0.01). In patients with oligodendroglioma, a higher KPS was associated with longer survival (HR 0.25; 95% CI 0.02-0.67; p = 0.05). Tumor resection (HR 0.43; 95% CI 0.22-0.86; p = 0.02) and wait-and-scan strategies (HR 0.34; 95% CI 0.14-0.79; p = 0.01) were associated with longer survival in patients with astrocytoma. CONCLUSION Tumor resection followed by a wait-and-scan strategy may yield excellent survival times, especially in patients with IDH-mutant grade 2 astrocytoma. Age appears not be an important predictor for survival in patients with IDH-mutant gliomas.

Biphenotypic Sinonasal Sarcoma: Literature Review of a Peculiar Pathological Entity-The Neurosurgical Point of View.

Biphenotypic sinonasal sarcoma (BSNS) is a low-grade tumor of the sinonasal tract with frequent extension to the orbit and skull base. Due to its rare incidence and recent histopathological and molecular characterization, little data are available in regard to its natural history, treatment and surveillance protocol. A comprehensive literature review in Embase online electronic databases on BSNS was made. The analyzed factors included the patients' sex and age, presenting symptoms and signs, anatomical origin and pattern of growth of the tumor, immunohistochemical and molecular features, time to treatment, type of treatment, surgical approach, extent of resection, peri- and post-operative complications, adjuvant therapies, clinical outcome, recurrence and overall survival rates. This literature review involved 34 studies for an overall series of 149 cases of BSNS. The female (66.9%) and middle-aged populations (median 54.88 years old) were mainly affected. The most frequent clinical onset was nasal obstruction (81%), followed by facial discomfort (44%), epistaxis (15.5%) and ocular impairment (14.3%). Ethmoid sinus (67.8%) and nasal cavity (45.4%) were the most common anatomical site of tumor origin, while an extension to the orbit and skull base was registered in 28.7% and 24.5% of cases. Surgery was the main treatment, especially in the form of endoscopic endonasal approach (56.9%), and allowed for gross total resection in 79% of cases. The recurrence rate was 26.2%; three cases of tumor-related death were reported. Median follow-up was 4.6 years. Biphenotypic sinonasal sarcoma is a rare and unique tumoral entity in terms of biological and clinical behavior. Based on the current knowledge, surgery plays the leading role in treatment, accounting for gross total tumor resection in most cases, allowing for clinical symptom and sign resolution and presenting a low rate of perioperative complications. The type of approach and the aim of surgery should be assessed case by case according to patient and pathology features and the surgeon's experience, as well as the aim of the treatment. Further studies including large surgical series and with long follow-up are required to define prognostic factors and guidelines of treatment for this peculiar pathological entity.

Prognostic Value of Adding Blood and Lymphatic Vessel Invasion to the 8th Classification of TNM in Lung Cancer in Stages I and II

ObjectivesExpanding TNM staging system for lung cancer with the addition of new prognostic factors could enhance patient stratification and survival prediction. The goal of this study is to assess if TNM prognosis capacity could be improved by incorporating other pathological characteristics of surgical specimen. MethodsWe retrospectively reviewed lung cancer resections, stages I–II, performed between January 1st 2010 and May 1st 2019. We collected clinical variables and pathological characteristics, including vascular, lymphovascular and perineural invasion, STAS, necrosis and stromal features. Mortality and recurrence-free survival were assessed with univariable and multivariable Cox analysis. We explored how these factors would modify the TNM Harrel's index. Results629 tumors were analyzed. Median overall survival was 53.9 months. Median recurrence-free survival was 47.6 months. Specific survival at 3, 5 and 10 years was 90, 83 and 74%. Recurrence-free survival at 3, 5 and 10 years was 76, 70 and 65%.The multivariable analysis showed that overall survival was significantly related to TNM classification (p<0.0002), vascular infiltration (HR 1.93, CI 1.42–2.64, p<0.0001), lymphovascular invasion (HR 1.88, CI 1.30–2.71, p<0.0015) and necrosis (HR 1.74, CI 1.24–2.45, p<0.0025). Harrell's index for TNM was 0.6139. Adding vascular, lymphovascular invasion and necrosis, it increased up to 0.6531.The multivariable analysis showed that specific survival was significantly related to TNM classification (p<0.001), vascular infiltration (HR 2.23, CI 1.44–3.46, p<0.001) and lymphovascular invasion (HR 1.85, CI 1.09–3.13, p<0.021). Harrell's index for TNM was 0.6645. Adding vascular and lymphovascular invasion, it increased up to 0.7103. Recurrence-free survival was related to TNM, vascular infiltration (HR 1.48, CI 1.05–2.09, p<0.023) and lymphovascular invasion (HR 2.40, CI 1.64–3.50, p<0.001). Harrell's index for TNM was 0.6264. Adding vascular and lymphovascular invasion, it increased up to 0.6794. ConclusionsIncluding vascular and angiolymphatic invasion in the staging system classification could better stratify patients at risk of recurrence and tumor-related death.

Tumor-associated macrophages induce epithelial-mesenchymal transition and promote lung metastasis in breast cancer by activating the IL-6/STAT3/TGM2 axis

Breast cancer is one of the most common tumors in the world and metastasis is the major cause of tumor-related death. Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment (TME) and often associated with cancer metastasis. Nevertheless, the mechanism by which TAMs regulate breast cancer metastasis remain unclear. In this study, we found that transglutaminase 2 (TGM2) could serve as a crucial target in the modulation of TAMs-induced epithelial-mesenchymal transition (EMT) and invasion of breast cancer cells. Further analysis revealed that IL-6 secreted from TAMs, which was capable of inducing TGM2 expression through the activation of the JAK/STAT3 signaling pathway. Subsequent luciferase reporter assays demonstrated that STAT3 binds to the TGM2 promoter region, thereby transcriptionally enhancing TGM2 expression. In conclusion, our current research has identified the IL-6/STAT3/TGM2 axis as a pivotal regulator in breast tumorigenesis caused by TAMs, presenting a novel target for the treatment of breast cancer.

Prognostic value of 18 F-FDG PET/CT in postoperative recurrence of retroperitoneal liposarcoma: a single-center retrospective study.

Recurrence is the leading cause of tumor-related death in retroperitoneal liposarcoma (RPLPS). Variant subtypes of RPLPS determine different recurrence 18 F]-fluoro-2-deoxy-D-glucose ( 18 F-FDG) PET/computed tomography (PET/CT). This study analyzed the characteristics of different histologic subtypes of 18 F-FDG PET/CT and their associations with recurrence and prognosis. Clinical-pathological information, 18 F-FDG PET/CT data, recurrence, and progression-free survivals (PFS) of 83 patients with RPLPS were collected. Maximum and peak standardized uptake values (SUV max and SUV peak , respectively) and mean CT value (CT mean ) of tumors were measured and correlated with histologic subtype. Receiver operating characteristics (ROC) curves were used to analyze the predictability for subtype and recurrence. Kaplan-Meier analysis examined SUV max and SUV peak as recurrence risk factors. Studied patients with different types of liposarcomas. Dedifferentiated liposarcomas (DDLPS) had higher SUV max and SUV peak than well-differentiated (WDLPS) and myxoid/round cell (MLPS) types. WDLPS had lower CT mean values compared to MLPS and DDLPS. Using ROC curves, determined cut-off values for SUV max (5.1) to differentiate DDLPS, SUV peak (3.0) for WDLPS, and CT mean (12.3 Hu) for WDLPS. These cut-offs were found to be best for predicting recurrence. Kaplan-Meier analysis showed that histologic subtype, SUV max , and SUV peak were all linked to recurrence-free survival. The use of SUV and CT features on 18 F-FDG PET/CT imaging may increase confidence in subtype diagnosis. Patients with SUV max > 5.1 or SUV peak > 3.0 suggest a poor prognosis.

Role of CENPL, DARS2, and PAICS in determining the prognosis of patients with lung adenocarcinoma.

Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers, and is the leading cause of tumor-related death. Lung adenocarcinoma (LUAD) is the most prevalent subtype of NSCLC. Although significant progress of LUAD treatment has been made under multimodal strategies, the prognosis of advanced LUAD is still poor due to recurrence and metastasis. There is still a lack of reliable markers to evaluate the LUAD prognosis. This study aims to explore novel biomarkers and construct a prognostic model to predict the prognosis of LUAD patients. The Genomic Data Commons-The Cancer Genome Atlas-Lung Adenocarcinoma (GDC-TCGA-LUAD) dataset was downloaded from the University of California, Santa Cruz (UCSC) Xena browser. The GSE72094 and GSE13213 datasets and corresponding clinical information were downloaded from the Gene Expression Omnibus (GEO) database. By analyzing these datasets using DESeq2 R package and Limma R package, differentially expressed genes (DEGs) were found. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to analyze possible enrichment pathways. A protein-protein interaction (PPI) network was constructed to explore possible relationship among DEGs by using the STRING database. A survival analysis was performed to identify reliable prognostic genes using the Kaplan-Meier method. A multi-omics analysis was performed using the Gene Set Cancer Analysis (GSCA). The Tumor Immune Estimation Score (TIMER) database was used to analyze the association between prognostic genes and immune infiltration. A Spearman correlation analysis was conducted to examine the correlation between prognostic genes and drug sensitivity. A multivariate Cox regression was used to identify independent prognostic factors. Next, a nomogram was constructed using the rms R package. Finally, the expressions of aspartyl-tRNA synthetase 2 (DARS2) and phosphoribosyl aminoimidazole carboxylase (PAICS) were detected using immunohistochemistry (IHC). We screened out 30 DEGs prior to functional enrichment and PPI network analysis revealing potential enrichment pathways and interactions of these DEGs. Then survival analysis revealed the CENPL, DARS2, and PAICS expression was negatively correlated with LUAD prognosis. Additionally, multi-omics analysis showed CENPL, DARS2, and PAICS expressions were significantly higher in LUAD tissues than normal tissues. CENPL, DARS2, and PAICS were all up-regulated in late stage and M1 stage. Correlation analysis indicated CENPL, DARS2, and PAICS may not be associated with activation or suppression of immune cells. Drug sensitivity analysis revealed many potentially effective drugs and small molecule compounds. Moreover, we successfully constructed a robust and stable nomogram by combining the DARS2 and PAICS expression with other clinicopathological variables. Finally, IHC results showed DARS2 and PAICS were significantly up-regulated in LUAD. The CENPL, DARS2, and PAICS expression was negatively correlated with LUAD prognosis. A prognostic model, which integrated DARS2, PAICS, and other clinicopathological variables, was able to effectively predict LUAD patients prognosis.

Identification of the tumor metastasis-related tumor subgroups overexpressed NENF in triple-negative breast cancer by single-cell transcriptomics

Tumor metastasis is a continuous and dynamic process and is a major cause of tumor-related death in triple-negative breast cancer. However, this biological process remains largely unknown in triple-negative breast cancer. The emergence of single-cell sequencing enables a deeper understanding of the tumor microenvironment and provides a new strategy for discovering the potential mechanism of tumor metastasis. Herein, we integrated the single-cell expression profiling of primary and metastatic triple-negative breast cancer by Seurat package. Nine tumor cell subgroups were identified. Enrichment analysis suggested tumor subgroups (C0, C4) were associated with tumor metastasis with poor prognosis in TNBC. Weighted gene co-expression network was constructed and identified NENF was a metastasis-related gene. Subsequently, RT-qPCR, Immunohistochemistry, and western blot confirmed NENF is highly expressed in TNBC tissues. And cell function assays indicated NENF promote cell invasion and migration through regulating EMT in TNBC. Finally, TIDE and Connectivity Map database suggest the candidate drugs for targeting NENF. In conclusion, our findings provide a new insight into the progression and metastasis of TNBC and uncover NENF may be a prognostic biomarker and potential therapy targets.

Prognostic prediction signature and molecular subtype for liver cancer: A CTC/CTM‑related gene prediction model and independent external validation.

Liver cancer is the second leading cause of tumor-related death worldwide, and a serious threat to lives and health. Circulating tumor cells (CTCs) facilitate the progression of various cancers, including liver cancer. The relationship between CTC/circulating tumor microemboli-related genes (CRGs) and the prognosis of liver cancer is unclear. The aim of the present study was to identify CTC/circulating tumour microemboli-related genes (CRGs) in hepatocellular carcinoma and to investigate their clinical significance. Transcriptomic data from The Cancer Genome Atlas (International Cancer Genome Consortium (ICGC) and GSE117623 databases were combined, and differentially expressed CRGs were identified. These were subsequently analyzed via least absolute shrinkage and selection operator and multivariate Cox analyses, and a five-gene risk signature was constructed. The signature was validated in the ICGC and GSE14520 dataset with survival analysis and receiver operating characteristic curve analysis. Immunocyte infiltration, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE), and the somatic mutation rate were also compared between high- and low-risk groups, based on the median predictive index, to further evaluate the immunotherapeutic value of the model. Molecular subtypes of liver cancer were characterized by the non-negative matrix factorization method and potential therapeutic compounds were evaluated for different subtypes. Nomograms were utilized to predict the prognosis of patients, and the signature was compared with previous literature models. Additionally, the biological function of one of the CRGs, tumor protein p53 inducible protein 3 (TP53I3), in liver cancer was further explored through in vitro experiments. Analysis of the prognostic characteristics of the five CRGs led to the identification of two liver cancer subtypes. Patients in the low-risk group had a longer survival compared with those in the high-risk group, and patients in the latter group were associated with a higher TMB, immunocyte infiltration and somatic mutation rate, and lower TIDE scores. The prognostic profile was validated in the ICGC and GSE14520 datasets and exhibited a good predictive performance. In vitro analysis showed that the knockdown of TP53I3 suppressed liver cancer cell proliferation. In summary, CRGs were used to develop a new prognostic signature to predict the prognosis of patients with liver cancer. This signature may be used to assess the prognosis of patients and may provide new insights for clinical management strategies. In addition, TP53I3 is potentially a therapeutic target for liver cancer.

Retinoblastoma Outcomes Based on the 8th Edition American Joint Committee on Cancer Pathological Classification in 1411 Patients

PurposeTo evaluate the outcomes of retinoblastoma (RB) based on the 8th edition of the American Joint Committee on Cancer (AJCC) pathological classification in a global cohort of patients. DesignRetrospective, multicentre, intercontinental collaborative study Participants1411 patients Intervention(s)Primary enucleation with/without adjuvant chemotherapy/radiotherapy Main outcomes(s)Orbital tumor recurrence, tumor-related metastasis, tumor-related death ResultsBased on the 8th edition AJCC pathological classification, 645 (46%) eyes belonged to pT1, 164 (11%) to pT2, 493 (35%) to pT3, and 109 (8%) to pT4 categories. At a mean follow-up of 38 months (median, 35 months; <1-149 months), orbital tumor recurrence was seen in 8 (1%), 5 (3%), 22 (4%) and 25 (23%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively; tumor-related metastasis was seen in 7 (1%), 5 (3%), 40 (8%), and 46 (43%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively; tumor-related death was seen in 12 (2%), 7 (4%), 64 (13%), and 64 (59%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively. Multivariate Cox proportional hazards analysis of outcomes revealed pT category and adjuvant therapy as independent predictors of outcomes. Categories pT3b (p=0.005), pT3c (p<0.001), pT3d (p<0.001), and pT4 (p<0.001) had a greater hazard for orbital recurrence; categories pT2a (p=0.015), pT3a (p<0.001), pT3b (p<0.001), pT3c (p<0.001), pT3d (p<0.001) and pT4 (p<0.001) had a greater hazard for tumor-related metastasis; and categories pT2a (p=0.068), pT2b (p=0.004), pT3a (p<0.001), pT3b (p<0.001), pT3c (p<0.001), pT3d (p<0.001) and pT4 (p<0.001) had a greater hazard for tumor-related death when compared to the pT1 category. Patients who did not receive adjuvant therapy had greater hazards of orbital tumor recurrence in categories pT3b (p=0.005), pT3c (p=0.003), and pT4 (p=0.002); greater hazards of tumor-related metastasis in categories pT3a (p=0.001), pT3b (p=0.01), pT3c (p=0.001), and pT4 (p=0.007); and tumor-related death in categories pT3a (p<0.001), pT3b (p=0.009), pT3c (p=0.018), and pT4 (p<0.001) when compared to those who received adjuvant therapy. ConclusionThe 8th edition AJCC pathological classification predicts outcomes in patients undergoing primary enucleation for RB, and adjuvant therapy is associated with a lower risk of orbital recurrence, tumor-related metastasis, and tumor-related death in the pT3 and pT4 categories.

Chitosan-based biomaterial delivery strategies for hepatocellular carcinoma.

Hepatocellular carcinoma accounts for 80% of primary liver cancers, is the most common primary liver malignancy. Hepatocellular carcinoma is the third leading cause of tumor-related deaths worldwide, with a 5-year survival rate of approximately 18%. Chemotherapy, although commonly used for hepatocellular carcinoma treatment, is limited by systemic toxicity and drug resistance. Improving targeted delivery of chemotherapy drugs to tumor cells without causing systemic side effects is a current research focus. Chitosan, a biopolymer derived from chitin, possesses good biocompatibility and biodegradability, making it suitable for drug delivery. Enhanced chitosan formulations retain the anti-tumor properties while improving stability. Chitosan-based biomaterials promote hepatocellular carcinoma apoptosis, exhibit antioxidant and anti-inflammatory effects, inhibit tumor angiogenesis, and improve extracellular matrix remodeling for enhanced anti-tumor therapy. We summarized published experimental papers by querying them. This review discusses the physicochemical properties of chitosan, its application in hepatocellular carcinoma treatment, and the challenges faced by chitosan-based biomaterials.

Four Cases of Bladder Cancer in Young Patients with Severe Motor and Intellectual Disabilities

Recent advances in medical and nursing care have improved the prognosis of patients with severe motor and intellectual disabilities (SMID). However,there has been a proportionate increase in the incidence of malignant tumor-related deaths in this population owing to their prolonged survival. In this study,we reviewed the clinical characteristics of four bladder cancers in young SMID patients treated at our hospital. In all patients,a diagnosis of a bladder tumor was made after a referral from the family medical department to the urology department ; the median time from the first symptom to the diagnosis was 12.5 months (range : 0-17 months). In clinical staging,two patients had non-invasive cancer,while the other two had invasive bladder cancer (one patient with cN1). Radical cystectomy with ileal conduit was performed in three patients (pathological stages were pTa with CIS,pT3aN1,and pT3bN0),and transurethral bladder tumor ablation was performed in the fourth one. The median postoperative follow-up period was 134 months (range : 20-182 months). Three patients survived afterward,while one patient died due to other causes. These findings suggest that young SMID patients tend to have a more severe form of bladder cancer compared to the general young population. Therefore,complaints of gross hematuria and urinary symptoms in young patients with SMID need appropriate evaluation in cooperation with the family department for an early diagnosis.

Guidelines for holistic integrative management of pancreatic cancer

BackgroundPancreatic cancer ranks 10th in the incidence rate of malignant tumors in male, and 12th in female. Pancreatic cancer is the sixth leading cause of tumor-related deaths in China. It is a devastating malignancy with poor prognosis.MethodsDriven by the concept of "integrated medicine", the China Anti-Cancer Association Committee of Pancreatic Cancer organized relevant experts to complete this guideline.ResultsThis guideline aims to guide the integrated treatment and rehabilitation management of pancreatic cancer in an all-round way based on "Preventing, Screening, Diagnosing, Treating, and Rehabilitating".ConclusionsWe hope that this guideline will provide effective references for clinicians, so as to achieve the best treatment effects for pancreatic cancer patients in China.

The Recent Trends of Systemic Treatments and Locoregional Therapies for Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a hepatic malignancy that has a rapidly increasing incidence. CCA is anatomically classified into intrahepatic (iCCA) and extrahepatic (eCCA), which is further divided into perihilar (pCCA) and distal (dCCA) subtypes, with higher incidence rates in Asia. Despite its rarity, CCA has a low 5-year survival rate and remains the leading cause of primary liver tumor-related death over the past 10-20 years. The systemic therapy section discusses gemcitabine-based regimens as primary treatments, along with oxaliplatin-based options. Second-line therapy is limited but may include short-term infusional fluorouracil (FU) plus leucovorin (LV) and oxaliplatin. The adjuvant therapy section discusses approaches to improve overall survival (OS) post-surgery. However, only a minority of CCA patients qualify for surgical resection. In comparison to adjuvant therapies, neoadjuvant therapy for unresectable cases shows promise. Gemcitabine and cisplatin indicate potential benefits for patients awaiting liver transplantation. The addition of immunotherapies to chemotherapy in combination is discussed. Nivolumab and innovative approaches like CAR-T cells, TRBAs, and oncolytic viruses are explored. We aim in this review to provide a comprehensive report on the systemic and locoregional therapies for CCA.