Diverse Tumor Research Articles

Enhancing patient activation: a controlled implementation study of an interprofessional evidence-based counseling program for complementary and integrative healthcare in cancer patients ('CCC-Integrativ').

Complementary and integrative healthcare (CIH) is increasingly recognized as a valuable approach to empowering and activating cancer patients. Studies have shown that higher patient activation is positively associated with improved health outcomes and reduced healthcare costs. The CCC-Integrativ study aimed to assess the implementation of an evidence-based counseling service on CIH at four Comprehensive Cancer Centers (CCC) in Germany. In this controlled implementation study, the patient-level intervention included three CIH consultations within a 3-month period delivered by interprofessional teams of physicians and nurses. The primary endpoint was patient activation using the PAM-13 at baseline (T1) and post-intervention (T2), and compared between control (CO, receiving routine care) and the intervention group (IG) using an analysis of covariance. Missing data were handled with multiple imputations. Maintenance effects at 6-month follow-up (T3) were investigated using a linear mixed model. A total of n = 1128 oncology patients (CO = 443, IG = 685) with diverse tumor entities and cancer stages were included in the study. The overall mean baseline PAM-13 score was 69.74 (SD = 14.24) (n = 959 (85.0%)). A statistically significant between-group difference in post-intervention PAM-13 scores was observed (Fgroup(1, 1866.82) = 8.634, P = 0.003), with an adjusted mean difference of 2.22 PAM-points. Age, gender, tumor entity, disease stage, or CCC study site did not significantly predict post-treatment PAM-13 scores. The maintenance effect of the intervention was not statistically significant (FtimeXgroup(1, 3316.04) = 2.337, P = 0.096). Individually tailored counseling on CIH, offered by specifically trained, interprofessional teams, significantly improved patient activation. Given the established positive effects of higher patient activation, the implementation of such a program at cancer centers may yield beneficial outcomes for both patients and the healthcare system.

Ifosfamide-Induced Encephalopathy Managed Successfully with Methylene Blue in a Child with Wilms Tumor: A Case Report and Review of the Literature

Introduction: Ifosfamide is a crucial element in various chemotherapy protocols for the treatment of diverse solid tumors in both children and adults. Despite its efficacy, ifosfamide is associated with a rare yet severe adverse effect known as ifosfamide-induced encephalopathy (IIE), with a spectrum of signs and symptoms spanning from mild lethargy to coma or death. While approximately 13% of pediatric patients undergoing ifosfamide treatment experience IIE, consensus regarding its management remains controversial. Case Presentation: We present the case of a 4-year-old girl with stage 4 Wilms tumor and lung metastases who underwent radical nephrectomy followed by UH-1 chemotherapy. Imaging post-chemotherapy initially showed tumor clearance but later revealed relapse and lung metastasis. Following the initiation of the adjusted ICE protocol (ifosfamide, etoposide), the patient developed IIE, which was successfully treated with methylene blue. Conclusions: We strongly advise pediatric oncologists and hematologists to proactively consider the potential occurrence of IIE. Before starting ifosfamide therapy, patients should be assessed for possible risk factors associated with IIE. Considering methylene blue as a prophylactic measure is recommended for patients with significant risk factors. In cases where IIE manifests, using Methylene Blue to alleviate and reverse its signs and symptoms should be considered. Moreover, we highly encourage further research endeavors to validate methylene blue's effectiveness and determine its optimal dosage range, especially concerning pediatric patients.

Trop2-Targeted Molecular Imaging in Solid Tumors: Current Advances and Future Outlook.

Trophoblast cell surface antigen 2 (Trop2), a transmembrane glycoprotein, plays a dual role in physiological and pathological processes. In healthy tissues, Trop2 facilitates development and orchestrates intracellular calcium signaling. However, its overexpression in numerous solid tumors shifts its function toward driving cell proliferation and metastasis, thus leading to a poor prognosis. The clinical relevance of Trop2 is underscored by its utility as both a biomarker for diagnostic imaging and a target for therapy. Notably, the U.S. Food and Drug Administration (FDA) has approved sacituzumab govitecan (SG), a novel Trop2-targeted agent, for treating triple-negative breast cancer (TNBC) and refractory urothelial cancer, highlighting the significance of Trop2 in clinical oncology. Molecular imaging, a powerful tool for visualizing and quantifying biological phenomena at the molecular and cellular levels, has emerged as a critical technique for studying Trop2. This approach encompasses various modalities, including optical imaging, positron emission tomography (PET), single photon emission computed tomography (SPECT), and targeted antibodies labeled with radioactive isotopes. Incorporating Trop2-targeted molecular imaging into clinical practice is vital for the early detection, prognostic assessment, and treatment planning of a broad spectrum of solid tumors. Our review captures the latest progress in Trop2-targeted molecular imaging, focusing on both diagnostic and therapeutic applications across diverse tumor types, including lung, breast, gastric, pancreatic, prostate, and cervical cancers, as well as salivary gland carcinomas. We critically evaluate the current state by examining the relevant applications, diagnostic accuracy, therapeutic efficacy, and inherent limitations. Finally, we analyze the challenges impeding widespread clinical application and offer insights into strategies for advancing the field, thereby guiding future research endeavors.

TMIC-66. A NEW MOUSE MODEL THAT COMBINES DRIVER MUTATIONS TO ACCURATELY RECAPITULATE THE DIVERSE PHENOTYPES OF HUMAN GLIOBLASTOMA

Abstract To effectively beat glioblastoma, new pre-clinical models are needed: to dissect the biology of processes like migration and therapy resistance; to understand immune suppression and immunotherapy; and to use as a model for testing in therapeutic development. We have developed a new panel of glioblastoma mouse models, which engineer well-characterised glioblastoma driver mutations into an immortalised eGFP murine astrocyte-like cell. These “GEM-CLeM” are Genetically Engineered Mouse Cell Line Models. When transplanted intra-cranially into immunocompetent mice, these lines formed tumors with the key characteristics of glioblastoma – migratory and invasive, with rapid proliferation and infiltration of suppressive immune cells. The eGFP expression allowed detection of glioblastoma cells in situ and ex vivo, and the ability to readily distinguish tumor and stromal components of the tumors. Importantly, different combinations of driver mutations led to diverse tumor phenotypes. Loss of Pten with over-expression of mutant RAS generated tumors with 100% efficiency and the same time to tumor onset as the commonly used GL261 cell line. However, unlike GL261 tumors the Pten-RASV12 tumors had a highly invasive edge and extensive migration, and were full of pro-tumorigenic macrophages and monocytes, with very few T-cells or dendritic cells. Together, this recapitulated the phenotype of human wildtype IDH1 glioblastoma. In contrast, the very common EGFRvIII mutant did not drive tumor formation in combination with Pten loss. We also modelled mutant IDH glioblastoma by combining loss of p53 with overexpression of IDH1R132H. These were slow growing, densely packed tumors with extensive microglial involvement in addition to pro-tumorigenic macrophages. This GEM-CLeM system combines the benefits of the traditional genetically engineered mouse models with accessible, rapid, reproducible tumor formation. The GEM-CLeM lines are amenable to further genetic manipulation, so cells can be customised with other mutations to ask important biological questions in the presence of an intact tumor immune microenvironment.

Immune-based subgroups uncover diverse tumor immunogenicity and implications for prognosis and precision therapy in acute myeloid leukemia

BackgroundAlthough a considerable proportion of acute myeloid leukemia (AML) patients achieve remission through chemotherapy, relapse remains a recurring and significant event leading to treatment failure. This study aims to investigate the immune landscape in AML and its potential implications for prognosis and chemo-/immune-therapy.MethodsIntegrated analyses based on multiple sequencing datasets of AML were performed. Various algorithms estimated immune infiltration in AML samples. A subgroup prediction model was developed, and comprehensive bioinformatics and machine learning algorithms were applied to compare immune-based subgroups in relation to clinical features, mutational landscapes, immune characterizations, drug sensitivities, and cellular hierarchies at the single-cell level.ResultsTwo immune-based AML subgroups, G1 and G2, were identified. G1 demonstrated higher immune infiltration, a more monocytic phenotype, increased proportions of monocytes/macrophages, and higher FLT3, DNMT3A, and NPM1 mutation frequencies. It was associated with a poorer prognosis, lower proportions of various immune cell types and a lower T cell infiltration score (TIS). AML T-cell-based immunotherapy target antigens, including CLEC12A, Folate receptor β, IL1RAP and TIM3, showed higher expression levels in G1, while CD117, CD244, CD96, WT and TERT exhibited higher expression levels in G2. G1 samples demonstrated higher sensitivity to elesclomol and panobinostat but increased resistance to venetoclax compared to G2 samples. Moreover, we observed a positive correlation between sample immune infiltration and sample resistance to elesclomol and panobinostat, whereas a negative correlation was found with venetoclax resistance.ConclusionOur study enriches the current AML risk stratification and provides guidance for precision medicine in AML.

Enhanced Magnetic Resonance Imaging-Based Brain Tumor Classification with a Hybrid Swin Transformer and ResNet50V2 Model

Brain tumors can be serious; consequently, rapid and accurate detection is crucial. Nevertheless, a variety of obstacles, such as poor imaging resolution, doubts over the accuracy of data, a lack of diverse tumor classes and stages, and the possibility of misunderstanding, present challenges to achieve an accurate and final diagnosis. Effective brain cancer detection is crucial for patients’ safety and health. Deep learning systems provide the capability to assist radiologists in quickly and accurately detecting diagnoses. This study presents an innovative deep learning approach that utilizes the Swin Transformer. The suggested method entails integrating the Swin Transformer with the pretrained deep learning model Resnet50V2, called (SwT+Resnet50V2). The objective of this modification is to decrease memory utilization, enhance classification accuracy, and reduce training complexity. The self-attention mechanism of the Swin Transformer identifies distant relationships and captures the overall context. Resnet 50V2 improves both accuracy and training speed by extracting adaptive features from the Swin Transformer’s dependencies. We evaluate the proposed framework using two publicly accessible brain magnetic resonance imaging (MRI) datasets, each including two and four distinct classes, respectively. Employing data augmentation and transfer learning techniques enhances model performance, leading to more dependable and cost-effective training. The suggested model achieves an impressive accuracy of 99.9% on the binary-labeled dataset and 96.8% on the four-labeled dataset, outperforming the VGG16, MobileNetV2, Resnet50V2, EfficientNetV2B3, ConvNeXtTiny, and convolutional neural network (CNN) algorithms used for comparison. This demonstrates that the Swin transducer, when combined with Resnet50V2, is capable of accurately diagnosing brain tumors. This method leverages the combination of SwT+Resnet50V2 to create an innovative diagnostic tool. Radiologists have the potential to accelerate and improve the detection of brain tumors, leading to improved patient outcomes and reduced risks.

Detection of Alternative Lengthening of Telomeres via Chromogenic in situ Hybridization (ALT-CISH) for the Prognostication of PanNETs and Other Neoplasms

Molecular studies have shown ALT to be an important prognostic biomarker of shorter relapse-free survival (RFS) for patients with pancreatic neuroendocrine tumors (PanNETs) and other neoplasms. However, the preferred method of detecting ALT in tissue is by fluorescence in situ hybridization (FISH), which has several clinical limitations. These issues necessitate the creation of a chromogenic ALT assay that can be easily implemented into routine practice. A CISH assay was developed using genetically modified osteosarcoma cell lines, 20 normal pancreata, 20 ALT-positive PanNETs, and 20 ALT-negative PanNETs. Thereafter, it was validated on a multi-institutional cohort of 360 surgically resected PanNETs and correlated with multiple clinicopathologic features, RFS, and FISH results. Separately, 109 leiomyosarcomas (LMS) were evaluated by both CISH and FISH, and, similarly, the prognostic significance of ALT status was assessed. Upon optimization, ALT-CISH was identified in 112 of 360 (31%) primary PanNETs and was 100% concordant with FISH testing. ALT correlated with several adverse prognostic findings and distant metastasis (all p<0.004). The 5-year RFS for patients with ALT-positive PanNETs was 35% as compared to 94% for ALT-negative PanNETs. By multivariate analysis, ALT was an independent prognostic factor for shorter RFS. Similarly, ALT was associated with shorter RFS in LMS patients and, analogous to PanNETs, a negative, independent prognostic factor. ALT-CISH was developed and validated in not only PanNETs, but also sarcomas, specifically LMS. CISH testing has multiple advantages over FISH that facilitate its widespread clinical use in the detection of ALT and prognostication of patients with diverse neoplasms.

Multi‐omics graph convolutional networks for digestive system tumour classification and early‐late stage diagnosis

AbstractThe prevalence of digestive system tumours (DST) poses a significant challenge in the global crusade against cancer. These neoplasms constitute 20% of all documented cancer diagnoses and contribute to 22.5% of cancer‐related fatalities. The accurate diagnosis of DST is paramount for vigilant patient monitoring and the judicious selection of optimal treatments. Addressing this challenge, the authors introduce a novel methodology, denominated as the Multi‐omics Graph Transformer Convolutional Network (MGTCN). This innovative approach aims to discern various DST tumour types and proficiently discern between early‐late stage tumours, ensuring a high degree of accuracy. The MGTCN model incorporates the Graph Transformer Layer framework to meticulously transform the multi‐omics adjacency matrix, thereby illuminating potential associations among diverse samples. A rigorous experimental evaluation was undertaken on the DST dataset from The Cancer Genome Atlas to scrutinise the efficacy of the MGTCN model. The outcomes unequivocally underscore the efficiency and precision of MGTCN in diagnosing diverse DST tumour types and successfully discriminating between early‐late stage DST cases. The source code for this groundbreaking study is readily accessible for download at https://github.com/bigone1/MGTCN.

Functional Roles of Long Non-coding RNAs on Stem Cell-related Pathways in Glioblastoma

: Long non-coding RNAs (lncRNAs), characterized by their length exceeding 200 nucleotides and lack of protein-coding capacity, are intricately associated with a wide array of cellular processes, encompassing cell invasion, differentiation, proliferation, migration, apoptosis, and regeneration. Perturbations in lncRNA expression have been observed in numerous diseases and have emerged as pivotal players in the pathogenesis of diverse tumor types. Glioblastoma, a highly malignant primary tumor of the central nervous system (CNS), remains a formidable challenge even with the advent of novel therapeutic interventions, as primary glioblastomas invariably exhibit therapy resistance and aggressive behavior. Glioblastomas can arise from progenitor cells or neuroglial stem cells, revealing profound cellular heterogeneity, notably in the form of glioblastoma stem cells (GSCs) possessing stem-like properties. Glioblastomas comprise neural precursors that harbor essential characteristics of neural stem cells (NSCs). Several signaling pathways have been implicated in the regulation of self-renewal in both cancer cells and stem cells. In addition to their involvement in therapy resistance and survival of glioblastoma, lncRNAs are implicated in the modulation of GSC behaviors through diverse pathways and the intricate regulation of various genes and proteins. This review aims to comprehensively discuss the interplay between lncRNAs, their associated pathways, and GSCs, shedding light on their potential implications in glioblastoma.

Current advancements in PD-L1 modulation by CMTM6 in malignant tumors

Abstract The CKLF-like MARVEL transmembrane domain-containing protein 6 (CMTM6), a member of the chemokine-like factor superfamily, binds to programmed death-ligand 1 (PD-L1) on the cell membrane, thereby impeding PD-L1’s lysosomal degradation and sustaining its expression. In recent years, extensive studies on PD-L1 have provided insights into its function as an immunepoint inhibitor involved in tumor cell immune evasion. The specific interaction between CMTM6 and PD-L1 suggests a potential role in tumor cell immune evasion and suppression, potentially offering a novel therapeutic target for cancer immunotherapy. Currently, the research on CMTM6 and PD-L1 in diverse tumors and diseases is limited, but their significant roles are indicated. This article provides an overview of the impact of CMTM6 on the immune microenvironment in different types of cancer (such as lung cancer, breast cancer, and liver cancer), and summarizes the effects of CMTM6 on the occurrence and development of various tumors.

Veratridine, a plant-derived alkaloid, suppresses the hyperactive Rictor-mTORC2 pathway: a new targeted therapy for primary and metastatic colorectal cancer.

Despite considerable advances to improve colorectal cancer (CRC) survival over the last decade, therapeutic challenges remain due to the rapid metastatic dissemination of primary tumors and screening limitations. Meanwhile, the rise of CRC in younger adults (Early-onset CRC), commonly diagnosed with a metastatic form of the disease, shows the pressing need to develop more effective targeted therapies to decrease the high mortality rates associated with metastatic disease. Hyperactivation of the Rictor-mTORC2-AKT signaling pathway drives key metastatic players in diverse malignant tumors, including early- and late-onset colorectal cancer. Selective mTORC2 inhibitors are becoming a potential treatment strategy for CRC due to the therapeutic limitations of mTORC1 inhibitors. Veratridine (VTD), a lipid-soluble alkaloid extracted from Liliaceae plants, can transcriptionally increase UBXN2A, which induces 26S proteasomal degradation of the Rictor protein, a key member in the mTORC2 complex. Destabilization of Rictor protein by VTD decreases Akt phosphorylation on Ser 473 , which is responsible for metastatic signaling downstream of the mTORC2 pathway in diverse malignant tumors. VTD decreases the population of metastatic colon cancer stem cells and functions as an angiogenesis inhibitor. VTD effectively reduces the spheroid growth rate and restricts cell migration. Live cell migration and invasion assays alongside biomechanical-force-based experiments revealed that VTD suppresses colon cancer cell invasiveness and the ensuing risk of tumor metastasis. A CRC mouse model that mimics the natural stages of human sporadic CRC revealed that VTD treatment significantly decreases tumor growth in a UBXN2A-dependent manner. This study showed a novel mechanistic connection between a ubiquitin-like protein and mTORC2-dependent migration and invasion in CRC tumors. This study revealed the therapeutic benefit of selective inhibition of Rictor in CRC, particularly in tumors with a hyperactive Rictor-mTORC2 signaling pathway. Finally, this study opened a new platform for repurposing VTD, a supplemental anti-hypertension molecule, into an effective targeted therapy in CRC tumors.

Response assessment in pediatric neurooncology (RAPNO) criteria revisited: a practical navigation guide for neuroradiologists.

The Response Assessment in Pediatric Neuro-Oncology (RAPNO) Working Group is an international, collaborative network of experts dedicated to pediatric central nervous system (CNS) tumors that was created in 2011. Since then, six RAPNO articles with imaging guidelines for response assessment in diverse pediatric tumor subgroups have been published, namely: 1) medulloblastomas and leptomeningeal seeding tumors (2018), 2) pediatric high-grade gliomas (2020), 3) pediatric low-grade gliomas (2020), 4) diffuse intrinsic pontine gliomas (2020), 5) pediatric intracranial ependymomas (2022) and 6) pediatric craniopharyngiomas (2023). The purpose of this article is to review all current available RAPNO criteria using a systematized and comparative approach centered on the role of neuroradiologists and supported by neuroimaging examples. Special emphasis will be placed on clarification of core concepts as well as practical adoption aspects of the RAPNO guidelines, namely how and when to image the brain and/or the spine; how to interpret the imaging findings; which other clinical, therapeutic and laboratory variables to consider; and finally how to apply the information to attribute the final appropriate response assessment classification.

Germline variants of homology-directed repair or mismatch repair genes in cervical cancer.

While cervical cancer is associated with a persistent human papillomavirus (HPV) infection, the progression to cancer is influenced by genomic risk factors that have remained largely obscure. Pathogenic variants in genes of the homology-directed repair (HDR) or mismatch repair (MMR) are known to predispose to diverse tumour entities including breast and ovarian cancer (HDR) or colon and endometrial cancer (MMR). We here investigate the spectrum of HDR and MMR germline variants in cervical cancer, with particular focus on the HPV status and histological subgroups. We performed targeted next-generation sequencing for 5 MMR genes and 12 HDR genes on 728 German patients with cervical dysplasia or invasive cancer. In total, 4% of our patients carried a pathogenic germline variant, based on ClinVar classifications and additional ESM1b and AlphaMissense predictions. These included 15 patients with truncating variants in HDR genes (BARD1, BRCA1, BRCA2, BRIP1, FANCM, RAD51D and SLX4). MMR-related gene variants were less prevalent and mainly of the missense type. While MMR-related gene variants tended to associate with adenocarcinomas, HDR gene variants were commonly observed in squamous cancers. While one patient with HPV-negative cancer carried a pathogenic MMR gene variant (in MSH6), the HDR germline variants were found in patients with HPV-positive cancers and tended to associate with HPV18. Taken together, our study supports a potentially risk-modifying role of MMR and HDR germline variants in cervical cancer but no association with HPV-negative status. These variants may be exploitable in future therapeutic managements.

Transient CAR T cells with specificity to oncofetal glycosaminoglycans in solid tumors.

Glycosaminoglycans are often deprioritized as targets for synthetic immunotherapy due to the complexity of glyco-epitopes and limited options for obtaining specific subtype binding. Solid tumors express proteoglycans that are modified with oncofetal chondroitin sulfate (CS), a modification normally restricted to the placenta. Here, we report the design and functionality of transient chimeric antigen receptor (CAR) T cells with selectivity to oncofetal CS. Following expression in T cells, the CAR could be "armed" with recombinant VAR2CSA lectins (rVAR2) to target tumor cells expressing oncofetal CS. While unarmed CAR T cells remained inactive in the presence of target cells, VAR2-armed CAR T cells displayed robust activation and the ability to eliminate diverse tumor cell types in vitro. Cytotoxicity of the CAR T cells was proportional to the concentration of rVAR2 available to the CAR, offering a potential molecular handle to finetune CAR T cell activity. In vivo, armed CAR T cells rapidly targeted bladder tumors and increased the survival of tumor-bearing mice. Thus, our work indicates that cancer-restricted glycosaminoglycans may be exploited as potential targets for CAR T cell therapy.

Covalent Modification of p53 by (E)-1-(4-Methylpiperazin-1-yl)-3-(5-nitrofuran-2-yl)prop-2-en-1-one.

TP53 is commonly mutated in cancer, giving rise to loss of wild-type tumor suppressor function and increases in gain-of-function oncogenic roles. Thus, inhibition of mutant p53 and reactivation of wild-type function represents a potential means to target diverse tumor types. (E)-1-(4-Methylpiperazin-1-yl)-3-(5-nitrofuran-2-yl)prop-2-en-1-one (NSC59984), first identified from a high-throughput screen, induces wild-type p53 signaling and antiproliferative effects while inhibiting mutant p53 gain-of-function activities. Here, we investigate the specific mechanism of action of NSC59984 against p53. We found that NSC59984 reacts with thiols via an unusual Michael addition at the α-carbon. Covalent modification of p53 Cys124 and Cys229 was observed both following in vitro reaction and upon treatment of cells. Finally, we used a biotinylated form of NSC59984 and, separately, thermal proteome profiling to examine off-target effects, identifying several metabolic proteins involved in cellular metabolism as potential targets. These results demonstrate that covalent modification of p53 by NSC59984 leads to increased wild-type activity and suggest that potential reaction with metabolic enzymes may contribute to antiproliferative function.

Potentiation of Tumor Hallmarks by the Loss of GULO, a Vitamin C Biosynthesis Gene in Humans.

Vitamin C plays a significant role in various physiological functions. Humans depend on external sources of vitamin C due to the loss of the L-gulono-γ-lactone oxidase (GULO) gene that contributes to the synthesis of vitamin C. During the evolutionary loss of the GULO gene, physical, chemical, and biological factors were different from the present environmental settings. Besides the evolutionary genetic loss of the GULO gene, there is a gap in the insightful discussion on the potential implications of the non-functional GULO gene towards the predisposition of humans to cancer that faces hostile and carcinogenic environments. Various methods by which vitamin C modulates cellular processes related to cancer, including DNA repair, epigenetic changes, and redox balance, are discussed. Furthermore, we present experimental and clinical evidence indicating that vitamin C deficiency promotes tumor growth, metastasis, and therapy resistance, emphasizing its potential as a cancer phenotypic modulator. Therapeutic implications of restoring vitamin C levels in cancer treatment range from improving the efficacy of conventional medicines to exploiting metabolic vulnerabilities in tumors. The relevance of assessing vitamin C status in cancer patients and the basis for additional research into vitamin C supplementation as an adjuvant therapy is emphasized. This paper presents a comprehensive overview of the implications associated with the functional deficiency of the GULO gene in human subjects exhibiting diverse tumor hallmarks, encompassing ECM remodeling, hypoxia, epigenetic reprogramming, oxidative stress, and drug responsiveness.

Long-term quality of survival after pediatric low-grade glioma.

Low-grade glioma is the most common brain tumor in children with different modes of treatment and a high overall survival. Low-grade glioma is considered a chronic disease, since residual tumor is present in many children. The tumor and its treatment lead to acquired brain injury with diverse consequences for later life based on factors like the diverse tumor locations, treatment(s) applied, neurofibromatosis type 1, and age at diagnosis. An overview of affected domains is provided based upon cohort studies from literature and partially based on clinical experience with a practical approach regarding each domain of functioning in order to provide insight in the requirements for long-term care assistance after childhood low-grade glioma. The diverse domains that can potentially be affected are described as follows: motor function, speech, eating and swallowing, sensory functions, seizures, neuropathy, organ function after systemic treatment, late effects due to cranial radiation (vascular changes and secondary tumors, endocrine and hypothalamic function, sleep and energy, neuro-cognition and education, psychosocial effects, and quality of life. Insight in affected domains guides advices for medical follow-up, diagnostics, supportive instructions, and assistive measures per domain of functioning and provide insight in the requirements for long-term care assistance after childhood low-grade glioma.

H3K27me3 Loss in Central Nervous System Tumors: Diagnostic, Prognostic, and Therapeutic Implications.

Central nervous system (CNS) tumors represent a formidable clinical challenge due to their molecular complexity and varied prognostic outcomes. This review delves into the pivotal role of the epigenetic marker H3K27me3 in the development and treatment of CNS tumors. H3K27me3, specifically the trimethylation of lysine 27 on the histone H3 protein, plays a crucial role in regulating gene expression and maintaining chromatin architecture (e.g., in X-chromosome inactivation). Notably, a reduction in H3K27me3 levels, frequently tied to mutations in the H3 gene family such as H3F3A and HIST1H3B, is evident in diverse brain tumor variants, including the diffuse midline glioma characterized by the H3K27M mutation and certain pediatric high-grade gliomas. The loss of H3K27me3 has been linked to more aggressive behavior in meningiomas, with the trimethylation loss associated with significantly shorter recurrence-free survival (RFS) among grade 2 meningiomas, albeit not within grade 1 tumors. Pediatric posterior fossa ependymomas characterized by a lowered H3K27me3 and DNA hypomethylation exhibit poor prognosis, underscoring the prognostic significance of these epigenetic alterations in CNS tumors. Comprehending the role of H3K27me3 in CNS tumors is vital for advancing diagnostic tools and therapeutic interventions, with the goal of enhancing patient outcomes and quality of life. This review underscores the importance of ongoing investigations into H3K27me to refine and optimize management strategies for CNS tumors, paving the way for improved personalized medicine practices in oncology.

Computational Development of New Inhibitors for Apoptosis Stimulating Protein of p53 (iASPP) Using Pharmacophore Modeling, Docking, and MD Simulation Approaches

Inhibitor of apoptosis-stimulating protein of p53 (iASPP) overexpression is associated with diverse human tumors, including lung cancer, colorectal cancer, prostate cancer, acute leukemia, hepatocellular carcinoma, cervical cancer, and ovarian cancer. This study aims to find new and potent inhibitors for the iASPP drug target. Using pharmacophore-based virtual screening, molecular docking, and molecular dynamics simulation an integrated strategy was developed to find highly effective iASPP inhibitors. Subsequently, the pharmacophore model was employed as a screening query to find promising inhibitors from the ZINC database. Total 36/12000 hits were identified against the iASPP drug target. The binding mode of the promising identified inhibitors was predicted by a molecular docking study. To evaluate the stability of the newly identified inhibitors top 03 best docking scores compounds were subjected to MD simulation. MD simulation and binding energy calculation confirmed that the compounds including ZINC001361049159, ZINC001361124195, and ZINC001545869876 were stable. The MD simulation analysis indicated that among all the compounds ZINC001361049159 was the most potent. These newly designed iASPP inhibitors could be used as starting material to identify new and potent anti-cancer drugs.

Various Presentations of Neuroendocrine Tumors (NETs): A Study of 10 Cases

Neuroendocrine tumors (NETs) are rare and diverse neoplasms that can present with a wide range of symptoms, making diagnosis challenging. This study aims to describe the various presentations of NETs in a cohort of 10 patients, highlighting the importance of considering NETs in patients with nonspecific symptoms.