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Liquid Biopsy in Head and Neck Squamous Cell Carcinoma: A Molecular Perspective on Circulating Biomarkers and Their Clinical Translation.

Liquid biopsy, the analysis of tumor-derived material in blood, saliva, and other body fluids, is increasingly explored for the diagnosis, surveillance, and molecular characterization of head and neck squamous cell carcinoma (HNSCC). Its performance, however, is not uniform across the disease, and the reason is fundamentally molecular. human papillomavirus (HPV)-positive oropharyngeal cancers carry viral oncogenes that are absent from the host genome and therefore provide a near ideal, tumor specific circulating marker, whereas HPV-negative tumors are driven by a heterogeneous somatic landscap…

Immunohistochemistry analysis of P16INK4a in pre-invasive ocular surface squamous neoplasia tissue samples infected and not infected by human papilloma virus at an academic laboratory in Northern Tshwane.

Ocular surface squamous neoplasia (OSSN) encompasses a wide range of benign and malignant tumours that arise from the conjunctiva and cornea. Tumour progression involves various genetic and epigenetic changes affecting oncogenes. The tumour suppressor gene P16INK4a serves as a key biomarker for high-risk humanpailloma virus (HR-HPV) infection in squamous neoplasms. This study assessed the prognostic significance of P16INK4a in pre-invasive ocular surface squamous neoplasia tissue samples. This retrospective study analysed 58 formalin fixed paraffin embedded (FFPE) tissue samples of OSSN with k…

Signaling pathways in tobacco smoking-induced cervical carcinogenesis: Beyond HPV-mediated activation.

Tobacco smoking is a well-established cofactor for human papillomavirus (HPV) in the development of cervical cancer (CC), but it also contri … sitive cells, several signaling pathways are activated, encompassing the dysregulated expression of oncogenes governed by the PI3K/AKT axis, such as NF-κB, MMP-2, and p53. Additionally, pathways including Rps27a/Mdm2/p53, AKT/mTOR/4EBP1/eIF4E, EGFR/PI3K/AKT/c-Jun, and α-enolase-mediated glycolysis are also involved, alongside the activation of Ras‑Raf‑Mek1/ …

HuB/HuR inhibition decreases HPV E6 and E7 proteins, stabilizes p53, and induces integrated stress to impair cervical cancer cell growth.

High-risk human papillomaviruses (HR-HPVs) cause 95% of cervical cancers (CaCx) and a significant fraction of other anogenital and oropharyngeal cancers. Transcriptomic analyses have revealed that HR-HPVs differentially induce RNA binding proteins (RBPs) associated with cancer-related pathways. One of them, ELAVL2/HuB, is related to the ubiquitous, well-studied ELAVL1/HuR. But the role of either RBP in HPV pathobiology is unclear. In this study, we examined SRI-42127, an inhibitor of HuR, for its ability to curb CaCx growth in multiple model systems. We report that HR-HPV E6 and E7 oncogenes r…

ENDOCAN TUTHYREF network consensus recommendations: Refractory follicular-derived thyroid cancer.

Radioactive-iodine-refractory differentiated thyroid cancer (RAIR DTC) represents 3-5% of follicular-derived DTCs, with approximately 200-30 … lowly progressive disease. (3) Early tumor molecular testing should be performed to identify driver oncogenes such as BRAF mutation or RET/NTRK/ALK fusion, to optimize access to existing selective targeted therapies. (4) For symptomatic or progressive RAIR DTC, tyrosine multikinase inhibitors, such as sorafenib, lenvatinib or cabozantinib, are the standard …

Distinct epigenetic and transcriptional profiles of Epstein-Barr virus-positive and negative primary CNS lymphomas.

BACKGROUND: Epstein-Barr virus (EBV)+ and EBV- primary CNS lymphomas (PCNSL) carry distinct mutational landscapes, but their transcriptional … ranscriptional signature contained genes (GPR15, FCER2/CD23, SLAMF1/CD150) closely regulated by EBV oncogenes in B cells. Pathway enrichment analysis uncovered enhanced B-cell receptor (BCR) and WNT/beta-catenin signaling in EBV- lymphomas, whereas Interleukin-10, NOTCH, and viral life cycle pathways were upregulated in EBV+ PCNSL. Correspondingly, BCR-asso …

The clinical effects of miR-26a, miR-16, let-7, miR-128a and miR-223 in acromegaly.

BACKGROUND: MicroRNAs (miRNAs) have been shown to function either as oncogenes or tumor suppressors, depending on the cellular context. This study aimed to explore the potential involvement of specific miRNAs in pituitary tumorigenesis and to assess their association with clinical features in patients diagnosed with acromegaly. METHODS: The study comprised 39 acromegaly patients and 39 healthy controls who were matched for age and gender. Real-time PCR was used to determine the miR-26a, let-7, miR-16, miR-223 and miR-128a levels in peripheral blood. The patients' treatment methods, radiograph…

Epidrugs in cancer: mechanisms, applications, and future direction.

DNA methylation, histone modifications, and regulation of non-coding RNA are all epigenetic modifications affecting cancer cells of origin and progression. These changes lead to changed expression of genes, which in turn is the reason for cancer occurrence in the form of inhibition of tumor suppressor genes or activation of oncogenes. Epigenetic changes, as opposed to genetic mutations, are reversible; thus, they seem to be interesting targets for therapeutic interventions. Current review summarizes the various types of epidrugs -DNA methyltransferase inhibitors (DNMTis), histone deacetylase i…

Low-Grade Mucoepidermoid Carcinoma of the Parotid in a Pediatric Survivor of Hodgkin's Lymphoma.

Mucoepidermoid carcinoma (MEC) is an uncommon malignancy of the salivary glands in the pediatric population. MEC typically occurs as a secon … lls and unusual mitoses, and a superficial parotidectomy was recommended. Genetic testing for major oncogenes and tumor suppressor gene mutations was conducted. Results were negative for any significant genetic factors. Alkylating chemotherapy agents and immunosuppression increase the risk of secondary malignancies, although they have not been directly link …

Unraveling the gender-specific molecular landscape of lung squamous cell carcinoma progression.

Lung squamous cell carcinoma (LUSC) is a type of non-small cell lung cancer that is the most common and deadly type of lung cancer, originat … rt lncRNAs (PVT1, FAM13A-AS1, LINC00461, NAV2-AS5, PRICKLE2-AS1, and VCAN-AS1) that may function as oncogenes or tumor suppressors by regulating the expression of coding genes, such as RAB24, HECW2, LGR4, and FKBP5. These lncRNAs and coding genes may play important roles in LUSC development and progression.

Targeted design, synthesis, molecular simulation, ADME-T and in-vitro anticancer assessment of phenyl-substituted-thioxo-tetrahydro-pyrimidin-benzenesulfonamide derivatives as potential BRAFV600E/WT inhibitors.

BRAF is one of the most commonly mutated oncogenes in human cancers, with more than 90 % of mutations occurring at codon 600. Among these, BRAFV600E is the most prevalent, accounting for nearly 90 % of all BRAF codon 600 mutations, while the less frequent variants are collectively referred to as BRAFV600WT. BRAF mutations are reported across several cancers, with the highest frequency in malignant melanoma (70-90 %). To target these mutations, a series of phenyl-substituted thioxo-tetrahydro-pyrimidine-benzenesulfonamide hybrids in the [αC-OUT/DFG-IN] conformation were designed. Fourteen deriv…

Atezolizumab with carboplatin plus nab-paclitaxel combination therapy for advanced nonsquamous non-small cell lung cancer with impaired renal function: A multicenter, single-arm phase 2 trial (RESTART, LOGiK 2002).

BACKGROUND: The current standard of care for advanced non-small cell lung cancer (NSCLC) without driver oncogenes is platinum-based chemotherapy together with immune checkpoint inhibition. However, most phase 3 trials of such combination therapy have excluded patients with renal impairment, with prospective data on its efficacy and safety in such patients thus being limited. METHODS: This multicenter, single-arm phase 2 study enrolled chemotherapy-naïve individuals with advanced nonsquamous NSCLC and renal impairment defined as a creatinine clearance (CCr) of 15 to <45 mL/min. Patients receiv…

Combined exome and RNA-seq analysis in patients with rare non-syndromic inherited brain arteriovenous malformation suggests a novel function for PTPN13 in arterial specification.

Non-syndromic inherited brain arteriovenous malformation (bAVM) is a very rare condition whose molecular basis is still uncharacterized. In contrast, sporadic bAVM can arise following gain-of-function mutations in the KRAS and BRAF proto-oncogenes. The bAVM lesion is characterized by a direct arteriole-to-venule shunt and the absence of a normal capillary bed, due to impaired expression of endothelial differentiation markers and failed arterial specification. In this context, perturbation of EphrinB2-EphB4 reverse signaling plays a pivotal role. According to this knowledge, this study describe…

DNA methylation biomarkers for cervical cancer risk prediction in HIV-positive Nigerian women.

Cervical cancer (CC) remains a significant public health issue in low- and middle-income countries (LMICs), especially in Western sub-Sahara … hese biomarkers showed hypermethylation in tumor suppressor genes (e.g., PRMD8), hypomethylation in oncogenes (e.g., MIR520H), and aberrant methylation in genes related to HIV/HPV infection and oncogenesis (e.g., GNB5, LMO4, FOXK2, NMT1). A machine learning-based DNAm classifier achieved 92.9% sensitivity and 88.6% specificity in predicting CC risk, with hi …

Tracking clonal evolution during treatment in ovarian cancer using cell-free DNA.

Emergence of drug resistance is the main cause of therapeutic failure in patients with high-grade serous ovarian cancer (HGSOC)1. To study d … genomic features, including chromothripsis, whole-genome doubling, and high-level amplifications of oncogenes such as CCNE1, RAB25, MYC and NOTCH3. Phenotypic analysis of matched single-cell RNA sequencing data3 indicated pre-existing and clone-specific transcriptional states such as upregulation of epithelial-to-mesenchymal transition and VEGF pathways, li …

Conjunctival Melanoma: Current Management.

Conjunctival melanoma is a rare, potentially lethal cancer that mainly affects fair-skinned individuals. The tumor mostly arises from primary acquired melanosis (PAM) with atypia. The presentation of conjunctival melanoma varies and should be clinically differentiated from an array of ocular surface pigmented and nonpigmented lesions. Mutations in the oncogenes BRAF (V600E) and NRAS, and the tumor suppressor gene NF1, are associated with worse survival. UV signature mutations are frequently observed in the bulbar conjunctival melanoma. The TNM staging classifies conjunctival melanoma according…

Distinct origins of high-grade serous ovarian carcinoma: genetic and epigenetic evidence linking ovarian and fallopian tube epithelium to clinical outcomes and early detection.

High-grade serous ovarian carcinoma (HGSOC) is the most prevalent and aggressive subtype among ovarian cancers and is associated with poor prognosis. The molecular mechanism of HGSOC development and metastasis is complex and associated with genomic instability due to abnormal DNA repair systems. This leads to the loss of tumor suppressors and amplification of oncogenes that are accompanied by epigenetic alterations. Despite its name and complexity, there is debate about its origin; however, recent findings on genetic and epigenetic features in animal models and human samples suggest that fallo…

Precision design of an HLA-I-targeted multiepitope vaccine against human papillomavirus 16 oncoproteins E6/E7: integrated immunoinformatic and immunogenicity profiling.

Viral oncogenes E6 and E7 are ideal targets for therapeutic vaccines against human papillomavirus (HPV)-associated cervical cancer (CC). T cell-mediated immunity plays a crucial role in the clearance of HPV infection and regression of intraepithelial neoplasia. Current strategies for therapeutic vaccine development predominantly depend on immunoinformatic predictions of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocyte (CTL) epitopes. Three T-cell epitope prediction programs were used to identify HPV16 E6 and E7 epitopes restricted to HLA-A*02:01. Subsequently, in silico evaluati…

Лизин деметилаза 6 (KDM6): перспективная терапевтическая цель в области аутоиммунных расстройств и рака.

Эпигенетическая динамика, которая влияет на выражения генов независимо от изменений последовательности ДНК, играет ключевую роль в регулировании структуры хроматина и транскрипции. Среди этих модификаций подсемейство подметила 6 (KDM6) с помощью динамического метилирования и деметилирования гистона 3 лизины 27 (H3K27me2/3) являются ключевыми регуляторами как физиологических, так и патологических процессов. В иммунных клетках KDM6A и KDM6B совершенствуют транскрипцию про- и антивоспалительных генов, оказывая влияние на дифференциацию, поляризацию и активацию в моноцитах, макрофагах, дендритных

Совпадение в аннотации оригинала
Epigenetic dynamics, which influence gene expressions independent of DNA sequence alterations, play a pivotal role in regulating chromatin s … tosus, and multiple sclerosis. Concurrently, KDM6A and KDM6B can act as either tumor suppressors or oncogenes in a context-dependent manner, mediating cellular proliferation, DNA damage repair pathways, and immune evasion in cancers ranging from hematologic malignancies to solid tumors of the bladder, breast, and brain. Recent efforts to exploit this dualit …

MicroRNAs: Potential prognostic and theranostic biomarkers in chronic lymphocytic leukemia.

Small noncoding ribonucleic acids called microRNAs coordinate numerous critical physiological and biological processes such as cell division, proliferation, and death. These regulatory molecules interfere with the function of many genes by binding the 3'-UTR region of target mRNAs to inhibit their translation or even degrade them. Given that a large proportion of miRNAs behave as either tumor suppressors or oncogenes, any genetic or epigenetic aberration changeing their structure and/or function could initiate tumor formation and development. An example of such cancers is chronic lymphocytic l…