Tumor Behavior Research Articles

Cytoplasmic SALL4-A isoform expression as a diagnostic marker of less aggressive tumor behavior in gastric cancer.

Gastric cancer (GC) poses significant challenges globally, ranking fifth in incidence and fourth in cancer-related mortality. SALL4, a stem cell transcription factor with multiple isoforms, includes SALL4-A as its full-length form. This study aims to evaluate the diagnostic potential of SALL4-A isoform expression in GC and its clinical significance. Immunohistochemical (IHC) analysis was conducted on Tissue Micro Array (TMA) slides from 167 GC patients. Clinicopathological parameters were correlated with SALL4-A expression, and survival analysis was performed. Diagnostic performance was assessed using metrics such as sensitivity, specificity, and area under the curve (AUC). SALL4-A exhibited distinct cytoplasmic expression in GC, correlating with lower histological grade (p = 0.003) and TNM stage (p = 0.003), particularly in the intestinal subtype. Diagnostic evaluation showed an AUC of 0.803 for cytoplasmic expression, demonstrating high diagnostic potential. However, SALL4-A expression did not show significant prognostic value. Cytoplasmic SALL4-A expression in GC is associated with less aggressive tumor phenotypes and shows promise as a diagnostic marker. Further research is warranted to elucidate its mechanistic role and potential integration into clinical practice.

Human epidermal growth factor receptor-2/neu expression in gallbladder cancer is significantly associated with clinicopathological parameters and survival.

Anti-human epidermal growth factor receptor-2 (Her-2/neu) target therapy has substantially improved the disease outcome of patients with breast and gastric/gastroesophageal cancers characterized by Her-2/neu overexpression and/or amplification. Consequently, evaluating Her-2/neu expression in other cancers to predict response to Her-2/neu targeting agents emerges as a crucial approach. We aimed at investigating the positivity rate of this receptor in gallbladder cancer (GBC) and assess the relationship between Her-2/neu status, clinicopathological parameters and survival to identify patients who would benefit most from anti-Her-2/neu-targeted therapy. The Her-2/neu expression was correlated with clinicopathological parameters and survival of GBC cases. Total 235 surgically resected and histopathologically proven primary GBC cases were collected over a five-year period from January 1, 2017, and December 31, 2020. Her-2/neu expression in these cases was analyzed using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Employing testing algorithms (IHC scoring based on gastric cancer criteria, followed by FISH in equivocal cases), Her-2/neu positivity was identified in 43 (18.29%) GBC cases and was significantly associated with grade I tumors, tumor stage > T2, perineural invasion, surgical margin positivity and advanced TNM stage. The mean survival time for Her-2/neu-positive cases was 14 months (SE, 1.1; 95%CI, 11.7-16.06), while it was 20 months (SE, 0.69; 95%CI, 18.1-20.9) for Her-2-negative cases (p < 0.001). Her-2/neu is expressed in about one-fifth of GBC patients and is significantly associated with tumor behavior and patient survival. Utilizing novel targeted agents may hold the key to improving the prognosis of these patients.

Autophagy induced by metabolic processes leads to solid tumor cell metastatic dormancy and recurrence.

A crucial cellular mechanism that has a complex impact on the biology of cancer, particularly in solid tumors, is autophagy. This review explores how metabolic processes trigger autophagy, which helps metastatic tumor cells go dormant and recur. During metastasis, tumor cells frequently encounter severe stressors, such as low oxygen levels and nutritional deprivation, which causes them to activate autophagy as a survival tactic. This process allows cancer stem cells (CSCs) to withstand severe conditions while also preserving their features. After years of dormancy, dormant disseminated tumor cells (DTCs) may reappear as aggressive metastatic cancers. The capacity of autophagy to promote resistance to treatments and avoid immune detection is intimately related to this phenomenon. According to recent research, autophagy promotes processes, such as the epithelial-to-mesenchymal transition (EMT) and helps build a pre-metastatic niche, which makes treatment strategies more challenging. Autophagy may be a promising therapeutic target because of its dual function as a tumor suppressor in early-stage cancer and a survival promoter in advanced stages. To effectively treat metastatic diseases, it is crucial to comprehend how metabolic processes interact with autophagy and affect tumor behavior. In order to find novel therapeutic approaches that can interfere with these processes and improve patient outcomes, this study highlights the critical need for additional investigation into the mechanisms by which autophagy controls tumor dormancy and recurrence.

Radiomic Fingerprinting of the Peritumoral Edema in Brain Tumors

Background/Objectives: Tumor interactions with their surrounding environment, particularly in the case of peritumoral edema, play a significant role in tumor behavior and progression. While most studies focus on the radiomic features of the tumor core, this work investigates whether peritumoral edema exhibits distinct radiomic fingerprints specific to glioma (GLI), meningioma (MEN), and metastasis (MET). By analyzing these patterns, we aim to deepen our understanding of the tumor microenvironment’s role in tumor development and progression. Methods: Radiomic features were extracted from peritumoral edema regions in T1-weighted (T1), post-gadolinium T1-weighted (T1-c), T2-weighted (T2), and T2 Fluid-Attenuated Inversion Recovery (T2-FLAIR) sequences. Three classification tasks using those features were then conducted: differentiating between Low-Grade Glioma (LGG) and High-Grade Glioma (HGG), distinguishing GLI from MET and MEN, and examining all four tumor types, i.e., LGG, HGG, MET, and MEN, to observe how tumor-specific signatures manifest in peritumoral edema. Model performance was assessed using balanced accuracy derived from 10-fold cross-validation. Results: The radiomic fingerprints specific to tumor types were more distinct in the peritumoral regions of T1-c images compared to other modalities. The best models, utilizing all features extracted from the peritumoral regions of T1-c images, achieved balanced accuracies of 0.86, 0.81, and 0.76 for the LGG-HGG, GLI-MET-MEN, and LGG-HGG-MET-MEN tasks, respectively. Conclusions: This study demonstrates that peritumoral edema, as characterized by radiomic features extracted from MRIs, contains fingerprints specific to tumor type, providing a non-invasive approach to understanding tumor-brain interactions. The results of this study hold the potential for predicting recurrence, distinguishing progression from pseudo-progression, and assessing treatment-induced changes, particularly in gliomas.

High expression of ARPC1B promotes the proliferation and apoptosis of clear cell renal cell carcinoma cells, leading to a poor prognosis.

ARPC1B has been identified as a key regulator of malignant biological behavior in various tumors. However, its specific role in clear cell renal cell carcinoma (ccRCC) remains poorly understood. This study aims to evaluate the influence of ARPC1B on the prognosis and disease progression in ccRCC patients. Multi-omics data and clinical information from public databases were analyzed to determine the associations between ARPC1B and prognosis, clinical features, immune microenvironment, and drug sensitivity in ccRCC. Co-expression and gene set enrichment analyses were conducted to elucidate the potential role of ARPC1B in ccRCC pathogenesis. Functional assays, including RT-qPCR, CCK8 assays, colony formation assays, immunofluorescence, immunohistochemistry, and xenograft tumor formation in nude mice, were performed to assess ARPC1B's impact on cell proliferation and apoptosis. Flow cytometry and Western blotting were further employed to investigate the underlying molecular mechanisms of ARPC1B in ccRCC. ARPC1B expression was significantly elevated in ccRCC and associated with an unfavorable prognosis. Both independent and meta-analyses confirmed that ARPC1B is an independent prognostic risk factor in ccRCC. Furthermore, ARPC1B expression significantly correlated with the immune microenvironment and drug sensitivity. In vitro, experiments demonstrated that ARPC1B knockdown suppressed ccRCC cell proliferation and induced apoptosis through the BAX-Bcl-2/c-caspase3/c-PARP axis, which was further validated by in vivo studies. ARPC1B overexpression is associated with poor prognosis, altered immune status, and drug sensitivity in ccRCC. Furthermore, ARPC1B promotes the malignant behavior of ccRCC cells and holds potential as a prognostic biomarker and therapeutic target for ccRCC.

Arginine and colorectal cancer: Exploring arginine-related therapeutic strategies and novel insights into cancer immunotherapies.

Concerning the progression of societies and the evolution of lifestyle and dietary habits, the potential for the development of human malignancies, particularly colorectal cancer (CRC), has markedly escalated, positioning it as one of the most prevalent and lethal forms of cancer globally. Empirical evidence indicates that the metabolic processes of cancerous and healthy cells can significantly impact immune responses and the fate of tumors. Arginine, a multifaceted amino acid, assumes a crucial and paradoxical role in various metabolic pathways, as certain tumors exhibit arginine auxotrophy while others do not. Notably, CRC is classified as arginine non-auxotrophic, possessing the ability to synthesize arginine from citrulline. Systemic arginine deprivation and the inhibition of arginine uptake represent two prevalent therapeutic strategies in oncological treatment. However, given the divergent behaviors of tumors concerning the metabolism and synthesis of arginine, one of these therapeutic approaches-namely systemic arginine deprivation-does not apply to CRC. This review elucidates the characteristics of arginine uptake inhibition and systemic arginine deprivation alongside their respective benefits and limitations in CRC. Furthermore, the involvement of arginine in immunotherapeutic strategies is examined in light of the most recent discoveries on various human malignancies.

Tumor Budding: A Prognostic Marker of Aggressiveness and Metastatic Potential in Epithelial Cancers, with a Focus on Colorectal and Urothelial Carcinomas

A hallmark of malignancy is the ability of a tumor to disseminate and metastasize, a process that requires specific cellular adaptations. The American Joint Committee on Cancer developed the TNM staging system to classify malignancies and guide treatment strategies, reflecting the biological behavior and clinical outcomes of cancers. Despite its usefulness, ongoing efforts aim to identify additional diagnostic and prognostic parameters to improve accuracy and treatment outcomes. One such parameter is tumor budding, a distinctive morphological feature observed in epithelial cancers. tumor budding is characterized by single tumor cells or small clusters of up to four cells that detach from the invasive front and invade the surrounding stroma. First described in colorectal cancer, tumor budding has since been widely investigated and recognized as a predictor of adverse outcomes, including lymph node invasion, local and distant metastasis, lymphovascular invasion, and poor survival rates across multiple cancer types. Independent of pathological stage, tumor budding correlates with aggressive tumor behavior, highlighting its prognostic significance. In urothelial cancers, tumor budding has been linked to stage progression, distant metastasis, and survival outcomes, particularly in non-muscle invasive bladder cancer and muscle-invasive bladder cancer. This review examines the mechanisms underlying tumor budding, its clinical significance across various tumor types, and its prognostic implications in epithelial cancers. Understanding these factors could provide valuable insights into integrating tumor budding into routine pathological assessments and improving cancer management strategies.

Uncovering the role of oncogenic HER2 variants as drivers of pancreatic cancer.

772 Background: The therapeutic resistance of pancreatic ductal adenocarcinoma (PDAC) to conventional cytotoxic therapy underscores the need for advances in targeted molecular therapeutics. Previous studies have reported approximately 2% of PDAC patients with HER2 gene amplification. While anti- HER2 cancer therapy has yielded success in other disease sites, it has had minimal reported benefit in PDAC. Multiple HER2 isoforms exist that are generated either by loss of exon 16 ( d16 HER2 ), or through N-terminal truncations ( p95 HER2 ). These isoforms are implicated in differential tumor behavior and response to anti-HER2 therapy in the breast but have not been investigated in PDAC. Herein, we hypothesize that these isoforms may underlie the observed resistance to HER2 therapy in PDAC. Methods: To test for the presence of HER2 structural variants within human PDAC, a tissue microarray was constructed of fifty-one primary tumor samples and two metastatic samples. Multiplex immunohistochemistry (mIHC) was performed for staining of the extracellular N-terminal and intracellular C-terminal HER2 domains. We then utilized our previously described HER2 + cancer rainbow (Crainbow) mouse model in which human wild-type HER2 ( WT HER2 ), d16 HER2 , and p95 HER2 were expressed in the same mouse along with fluorescent protein reporters. HER2 Crainbow mice were crossed with PDX1-Cre recombinase to initiate recombination and expression of each fluorescently labelled HER2 isoform during pancreas development. PDX1-Cre / HER2 Crainbow mice were followed for up to one year and sacrificed to lineage trace each isoform and register HER2 lineages with histopathology. Results: In our human data, four of fifty-three patient samples (three primary and one metastatic) had moderate-to-strong HER2 staining. All samples identified on mIHC as HER2 positive stained primarily for the p95 variant of HER2 , with absence of the N-terminal domain and preservation of the intracellular domain. In our transgenic mice, 65% of the mouse cohort developed pre-malignant low grade pancreatic intraepithelial neoplasia (PanIN) by eight weeks. At one year, 58.3% of mice demonstrated advanced high grade PanIN, and 25% developed invasive disease. Lineage tracing revealed that while early low grade PanIN began as polyclonal lesions, comprised of WT- , d16- , and p95 HER2 expressing cells, advanced PanIN and invasive disease were unanimously monoclonal with one dominant isoform arising. WT HER2 was represented abundantly in low grade disease, but high grade and invasive disease were predominantly driven by d16- and p95-HER2. Conclusions: Our data implicates the oncogenic d16- and p95 HER2 variants, rather than WT HER2 , as the primary drivers of HER2+ PDAC tumorigenesis. In breast p95 HER2 has been described as a known cause of Trastuzumab resistance. Therefore, future efforts will be aimed at characterizing the mechanisms driving therapeutic resistance in p95-HER2 PDAC tumors.

From infection to immortality: The role of HPV and telomerase in head and neck cancer.

Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of malignancies with multifactorial aetiologies. High-risk human papillomavirus (hrHPV) infections, particularly HPV16, and the dysregulation of telomerase activity, specifically through its catalytic subunit, telomerase reverse transcriptase (TERT) are among the key contributors to HNSCC development and progression. HPV promotes oncogenesis via the E6 and E7 oncoproteins, which inactivate tumour suppressors TP53 and RB1, leading to unchecked cellular proliferation. Concurrently, telomerase activation plays a critical role in HNSCC by maintaining telomere length, thus enabling cellular immortality, and facilitating tumour development and progression. The interplay between HPV and telomerase is significant; HPV oncoprotein E6 enhances telomerase activity through multiple regulatory mechanisms, including upregulating TERT expression. Beyond telomere maintenance, TERT influences signalling pathways, cellular metabolism, and the tumour microenvironment, contributing to aggressive tumour behaviour and poor prognosis. This review integrates the roles of HPV and telomerase in HNSCC, focusing on their molecular mechanisms and interactions that drive carcinogenesis and influence disease progression. Understanding the synergistic effects of HPV and TERT in HNSCC may be crucial for risk stratification, prognostic assessment, and the development of novel therapeutic strategies targeting these specific molecular pathways.

Natural Source of Drugs Targeting Central Nervous System Tumors—Focus on NAD(P)H Oxidoreductase 1 (NQO1) Activity

Central nervous system (CNS) tumors involve a large and diverse group of malignancies that arise from various cell types within the brain tissue. Although there are advances in treatments, CNS tumors still remain challenging, due to their complex biology and the delicate nature of the surrounding tissue. NAD(P)H O=oxidoreductase 1 (NQO1) is an enzyme that plays a critical role in the detoxification of quinones, protecting cells from oxidative stress. In CNS tumors this enzyme is often overexpressed, which contributes to the resistance of tumor cells to chemotherapy by enhancing their antioxidant defenses. NQO1 influences the progression of CNS tumors by affecting downstream signaling pathways, such as those involving the transcription factor SNAIL, as well as others that are associated with tumor behavior. Plants represent a valuable source of numerous constituents with different chemical structures known to affect different molecular signaling pathways associated with different pathologies.

Revealing miRNAs' Janus-Faced Nature: Transforming Cold Tumours into Immunotherapy Hotspots and Overcoming Chemoresistance.

MicroRNA (miRNA) modulation has emerged as a promising strategy in cancer immunotherapy, particularly in converting "cold" tumors with limited immune cell infiltration into "hot" tumors responsive to immunotherapy. miRNAs regulate immune cell recruitment and activation within the tumor microenvironment, influencing tumor behavior targeting specific miRNAs in cold tumors aims to enhance the immune response, potentially improving therapeutic efficacy. Despite ongoing research challenges, such as tumor complexity and treatment resistance, miRNA-based therapies offer personalized approaches with potential ethical considerations. Advances in miRNA profiling may enable early cancer detection and tailored treatments, underscoring its role in future oncology. This review sheds light on the role of miRNA in cold and hot tumor microenvironments, how they modulate depending on the tumor niche and the current research challenges in implementing miRNA-based therapies include the complexity of tumors and their heterogeneity, which makes it difficult to identify the most relevant miRNAs to target. Additionally, treatment resistance can develop over time, reducing the effectiveness of miRNA modulation. Despite these challenges, ongoing research and advancements in miRNA profiling hold promise for overcoming these obstacles and improving the outcomes of cancer immunotherapy. To overcome the challenges of identifying relevant miRNAs to target, researchers can employ high-throughput sequencing techniques to comprehensively profile miRNA expression in different tumor subtypes. They can also utilize bioinformatics tools and databases to analyze the vast amount of miRNA-related data and identify potential candidate miRNAs. Furthermore, collaborations between scientists and clinicians can help validate the functional significance of identified miRNAs and their potential as therapeutic targets.

Epstein-Barr virus status drives morphological and molecular intra-tumour heterogeneity in gastric cancer: insights from a case report and literature review.

This case report describes a rare case of bi-phenotypic gastric cancer with two distinct, but clonally related, histological components. The first component, associated with Epstein-Barr virus (EBV) infection, exhibited the morphological features of gastric carcinoma with lymphoid stroma, suggesting that EBV, as an effective immunogenic factor, may trigger a prominent immune response within the tumour microenvironment. The second component, which was EBV-negative, displayed tubular/papillary morphology and features of increased biological aggressiveness, such as high-grade areas and lymphatic invasion. Immunohistochemical and molecular studies confirmed that, despite the differing morphologies and immunophenotypes, both components were clonally related, with the EBV-negative area showing more complex DNA aberrations, reminiscent of chromosomally instable (CIN) lesions. This case describes clonally related EBV-positive and -negative components within a single gastric cancer, contributing to a better understanding of EBV role in tumour heterogeneity and progression and highlights the impact of EBV loss on tumour behaviour.

Radiogenomics and machine learning predict oncogenic signaling pathways in glioblastoma

BackgroundGlioblastoma (GBM) is a highly aggressive brain tumor associated with a poor patient prognosis. The survival rate remains low despite standard therapies, highlighting the urgent need for novel treatment strategies. Advanced imaging techniques, particularly magnetic resonance imaging (MRI), are crucial in assessing GBM. Disruptions in various oncogenic signaling pathways, such as Receptor Tyrosine Kinase (RTK)-Ras-Extracellular signal-regulated kinase (ERK) signaling, Phosphoinositide 3- Kinases (PI3Ks), tumor protein p53 (TP53), and Neurogenic locus notch homolog protein (NOTCH), contribute to the development of different tumor types, each exhibiting distinct morphological and phenotypic features that can be observed at a microscopic level. However, identifying genetic abnormalities for targeted therapy often requires invasive procedures, prompting exploration into non-invasive approaches like radiogenomics. This study explores the utility of radiogenomics and machine learning (ML) in predicting these oncogenic signaling pathways in GBM patients.MethodsWe collected post-operative MRI scans (T1w, T1c, FLAIR, T2w) from the BRATS-19 dataset, including scans from patients with both GBM and LGG, linked to genetic and clinical data via TCGA and CPTAC. Signaling pathway data was manually extracted from cBioPortal. Radiomic features were extracted from four MRI modalities using PyRadiomics. Dimensionality reduction and feature selection were applied and Data imbalance was addressed with SMOTE. Five ML models were trained to predict signaling pathways, with Grid Search optimizing hyperparameters and 5-fold cross-validation ensuring unbiased performance. Each model’s performance was evaluated using various metrics on test data.ResultsOur results showed a positive association between most signaling pathways and the radiomic features derived from MRI scans. The best models achieved high AUC scores, namely 0.7 for RTK-RAS, 0.8 for PI3K, 0.75 for TP53, and 0.4 for NOTCH, and therefore, demonstrated the potential of ML models in accurately predicting oncogenic signaling pathways from radiomic features, thereby informing personalized therapeutic approaches and improving patient outcomes.ConclusionWe present a novel approach for the non-invasive prediction of deregulation in oncogenic signaling pathways in glioblastoma (GBM) by integrating radiogenomic data with machine learning models. This research contributes to advancing precision medicine in GBM management, highlighting the importance of integrating radiomics with genomic data to understand tumor behavior and treatment response better.

Transcriptome-Based Survival Analysis Identifies MAP4K4 as a Prognostic Marker in Gastric Cancer with Microsatellite Instability

Background/Objectives: Gastric cancer (GC) is a highly aggressive malignancy with diverse molecular subtypes. While microsatellite instability (MSI) GC generally carries a favorable prognosis, a subset of patients experiences poor outcomes, highlighting the need for refined prognostic markers. Methods: This study utilized transcriptomic and clinical data from two independent cohorts, The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG), to identify novel prognostic genes in MSI-GC. Results: Through rigorous survival analysis, we identified high MAP4K4 expression (MAP4K4high) as an independent and robust predictor of poor overall survival (OS) and disease-free survival (DFS) specifically within the MSI-GC subtype. MAP4K4high was associated with increased hazard ratios for both OS and DFS in both cohorts, even after adjusting for clinicopathological factors. Further analysis revealed that MAP4K4high MSI-GC tumors exhibit a distinct molecular profile characterized by increased extracellular matrix remodeling, epithelial–mesenchymal transition, and a microenvironment enriched in monocytes and cancer-associated fibroblasts (CAFs). Notably, a subgroup of MSI-GC patients with a CIN-like phenotype and high MAP4K4 expression exhibited particularly dismal outcomes. Conclusions: Our findings establish MAP4K4 as a promising prognostic biomarker for risk stratification in MSI-GC and suggest its potential role in driving aggressive tumor behavior through modulation of the tumor microenvironment.

Abstract A007: Artificial intelligence in radiation therapy: Bringing in a new era of cancer therapy, accurate and fast

Abstract Introduction: The application of AI in RT has been adopted as innovative method that seeks to enhance accuracy, effectiveness and patient outcome of cancer treatment. This aims to understand current and potential uses of AI-based tools in RT; from planning, monitoring during therapy, adaptive approach, and after treatment assessment. This study defines the role of AI in facilitating decision-making, made to define treatment plans, and to organize the clinical practice in order to improve the therapeutic outcomes and provide individualized approach to the cancer patients. Methods and Experimental Procedures: Radiation therapy work flows which integrated AI algorithms for treatment planning and delivery were examined in a retrospective manner. Imaging data was used to predict tumor behavior and develop the best treatment plan since the models employed by practitioners involved machine learning. Another application of AI was for the shape matching of its patient anatomy during treatment and came up with better matching for therapy adjustments. This involved data from multiple clinical centers employing AI-assisted techniques for prostate, lung as well head and neck cancers. These QA procedures implemented with the help of AI were assessed with respect to their capability in identifying errors and maintaining dose accuracy. Results: Initial data showed that AI optimizes accuracy and time in treatment planning by streamlining the processes of outlining tumors and relevant tissues; planning time is cut in half in comparison with the conventional approach. Real-time positioning indicated by AI optimized adaptive therapy gave accuracy in tracking the anatomical variations thereby justifying the alterations in radiation delivery that enhanced the tumor control without affecting normal tissue. Automated quality assurance systems with AI capabilities successfully detected possible mistakes in the application of treatment processes and thus, decisively enhanced patients’ safety and minimized risks of radiation mishaps. The data also showed that models using AI enhanced accuracy in dose prediction and thus the overall treatment plans and results especially when the anatomy of a patient is unique and cannot easily be navigated. Conclusions: AI is becoming integrated into RT since it delivers, precision, personalization and efficiency that the industry desires. Advanced AI-based technologies help in treatment planning, facilitate monitoring and improve the technique of adaptive RT while also strengthening QA measures thus making patients safer and providing better therapeutic results. In the future, emerging technologies in AI offers prospects to address problems in radiation oncology for improved diagnosis and treatment of cancer. There is need for more clinical and research practice and development to actualize AI applications, remove the constraints and apply these systems in regular clinical services. The future of RT is going to be with AI incorporated in all the departments to ensure that cancer treatment is optimized for the benefit of the patient. Citation Format: Newtone Kisia. Artificial intelligence in radiation therapy: Bringing in a new era of cancer therapy, accurate and fast. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A007.

Dynamic contrast enhanced MRI in nodal lymphoma: correlation of quantitative MR perfusion parameters with lymphoma subtype, Lugano stage and Ki-67 index.

Research into the intratumoral microenvironment in lymphoma has been escalated along with improved survival and new targeted therapies with an intent to refine risk stratification and prognostication. Various studies have reported significance of quantitative DCE-MRI parameters for predicting biological behaviour of various tumors. This study is an endeavour to supplement the existing literature on quantitative DCE-MRI in nodal lymphoma. To study the correlation of quantitative DCE-MRI parameters of Ktrans, Kep and Ve with subtype, Lugano stage at diagnosis and Ki-67 proliferation index (PI) in nodal lymphoma. 33 patients of age > 12 years with newly diagnosed nodal lymphoma underwent DCE-MRI. Ktrans, Kep and Ve were generated from extended Tofts model and correlated with lymphoma subtype, Lugano staging and Ki-67 PI. Mean Ktrans and Kep values were significantly higher in non-Hodgkin's lymphoma (NHL) than in Hodgkin's lymphoma (HL). Considering Ki-67 PI value of > 45% as aggressive lymphoma, the mean Ktrans (659.37 x 10-3min-1 versus 288.00 x 10-3min-1, p < 0.001) and Kep (1256.63 x 10-3min-1 versus 689.82 x 10-3min-1, p = 0.004) values in aggressive lymphomas were significantly higher compared to non-aggressive lymphomas. ROC curve analysis revealed a threshold Ktrans value of ≥ 359 x 10-3min-1 and Kep value of ≥ 853 x10-3 min-1 for diagnosing aggressive lymphomas with a sensitivity of 95%, 90%, specificity of 100%,82% and diagnostic accuracy of 91.7%,86.7% respectively. There was no significant difference in DCE-MRI parameters of various Lugano stage subgroups. DCE-MRI parameters have the potential to non-invasively predict the subtype, aggression and Ki-67 PI in nodal lymphoma. The knowledge that Ktrans is higher in aggressive lymphomas is novel. It adds to previous literature regarding MR perfusion in various neoplasms.

Cancer Stem Cell Regulation as a Target of Therapeutic Intervention: Insights into Breast, Cervical and Lung Cancer.

Cancer Stem Cells (CSCs) play an important role in the development, resistance, and recurrence of many malignancies. These subpopulations of tumor cells have the potential to self-renew, differentiate, and resist conventional therapy, highlighting their importance in cancer etiology. This review explores the regulatory mechanisms of CSCs in breast, cervical, and lung cancers, highlighting their plasticity, self-renewal, and differentiation capabilities. CD44+/CD24- cells are a known marker for breast CSCs. Markers like as CD133 and ALDH have been discovered in cervical cancer CSCs. Similarly, in lung cancer, CSCs identified by CD44, CD133, and ALDH are linked to aggressive tumor behavior and poor therapy results. The commonalities between these tumors highlight the general necessity of targeting CSCs in treatment efforts. However, the intricacies of CSC activity, such as their interaction with the tumor microenvironment and particular signaling pathways differ between cancer types, demanding specialized methods. Wnt/β-catenin, Notch, and Hedgehog pathways are one of the essential signaling pathways, targeting them, may show ameliorative effects on breast, lung and cervical carcinomas and their respective CSCs. Pre-clinical data suggests targeting specific signaling pathways can eliminate CSCs, but ongoing clinical trials are on utilizing signaling pathway inhibitors in patients. In recent studies it has been reported that CAR T based targeting of specific markers may be used as combination therapy. Ongoing research related to nanobiotechnology can also play a significant role in diagnosis and treatment purpose targeting CSCs, as nanomaterials can be used for precise targeting and identification of CSCs. Further research into the targeting of signaling pathways and its precursors could prove to be right step into directing therapies towards CSCs for cancer therapy.

Increased nerve density adversely affects outcome in colorectal cancer and denervation suppresses tumor growth

BackgroundThe colon and rectum are highly innervated, with neural components within the tumor microenvironment playing a significant role in colorectal cancer (CRC) progression. While perineural invasion (PNI) is associated with poor prognosis in CRC, the impact of nerve density and diameter on tumor behavior remains unclear. This study aims to evaluate the prognostic value of nerve characteristics in CRC and to verify the impact of nerves on tumor growth.MethodsTissue samples from 129 CRC patients were stained with immunofluorescent markers NF-L and S100B to detect nerves. Nerve diameter and density were measured and normalized. Kaplan-Meier survival analysis and Cox regression models were used to identify prognostic factors. Prognostic models were established using receiver operating characteristic (ROC) curve analysis to assess the predictive value of neural factors. A murine chemical denervation model was employed to disrupt sympathetic nerves using 6-hydroxydopamine, inhibit muscarinic receptor 3 with darifenacin, and ablate sensory neurons with capsaicin.ResultsThe total nerve density was 0.72 ± 0.59/mm², with intratumoral (0.42 ± 0.40/mm²) being significantly lower than extratumoral regions (1.00 ± 0.75/mm²). The average nerve diameter was 28.14 ± 6.04 μm, with no significant difference between intratumoral (28.2 ± 7.65 μm) and extratumoral regions (27.86 ± 6.72 μm). PNI was observed in 65 patients (50.4%). PNI and high normalized nerve density (NND) were associated with shorter overall survival and disease-free survival in CRC patients, with PNI identified as an independent prognostic factor. Patients with PNI exhibit higher NND. Incorporating PNI and NND into ROC curve analysis improved the sensitivity and specificity of survival predictions. In the murine model, chemical denervation of sympathetic, parasympathetic, and sensory nerves significantly reduced rectal tumor volume.ConclusionsPNI and NND are critical factors influencing CRC patient survival and enhance the accuracy of survival prediction models. Moreover, chemical denervation effectively inhibits rectal tumor growth in vivo, highlighting the potential of neural targeting as a therapeutic strategy in CRC.

Gene mutation, clinical characteristics and pathology in resectable lung adenocarcinoma

ObjectiveWith the wide use of CT scan in clinical practice, more lung cancer was diagnosed in resectable stage. Pathological examination and genetic testing have become a routine procedure for lung adenocarcinoma following radical resection. This study analyzed special pathological components and gene mutations to explore their relationship with clinical characteristics and overall survival.MethodsClinical, pathological, and gene mutation data from 1,118 patients were collected. All patients underwent surgery at the Department of Thoracic Surgery, the Second Xiangya Hospital of Central South University. Patients were grouped based on pathological components and gene mutations. Differences in clinical features and overall survival were analyzed as well.ResultsPatients with mucinous, neuroendocrine, and poor-differentiated components were presented with more prognostic risk factors, including pleural invasion, carcinothrombosis, STAS, and advanced stages, along with varying frequencies of gene mutations. These factors significantly shortened overall survival. ALK and KRAS mutations were also associated with risk factors such as solid nodules, pleural invasion, STAS, and later stages. However, a significant reduction in overall survival was observed only in patients with the KRAS mutation. Relationship between gene mutations and pathological components still requires further investigation.ConclusionSpecial pathological components (mucinous, neuroendocrine, and poor-differentiated) and gene mutations had an influence on biological behavior of tumors, resulting in different clinical characteristics and prognosis.

Traditional Chinese Medicine-Based Nanoformulations for Enhanced Photothermal Therapy of Cancer.

Photothermal therapy (PTT) has shown promise in the ablation of small, unresectable tumors by boosting the tumor's temperature above 50 °C. However, the high local temperature-induced cancer cell necrosis could create severe local inflammation, which may deteriorate normal tissues and increase tumor spreading. Although mild photothermal therapy (MPTT) at 42-45 °C could avoid the undesired side effect to some extent with minimal nonspecific heat diffusion, the self-protective behavior of tumors during MPTT results in an unsatisfactory therapeutic effect. Inspired by the widespread applications of traditional Chinese medicine (TCM) in various ailments, we also extensively explored the use of TCM in PTT and MPTT. In this Review, we summarize the application and function of TCM in PTT and MPTT, including the following: (1) TCM improves the performance of PTT and MPTT by elevating the photothermal conversion ability of photothermal agents (PTAs) and overcoming the self-protective effect of tumors, (2) PTT enhances TCM-based chemotherapy by improving the sensitivity and cellular uptake of TCM in tumors, and (3) natural TCM and metal-chelated TCM-based nanoparticles could directly act as PTAs for carrier-free combination therapy. We expect this Review will further illuminate TCM's utility and applicability in cancer treatment and create new combination strategies for theragnostic use.