Vascular tumors mutations

Protein kinases play pivotal roles in various biological functions, influencing cell differentiation, promoting survival, and regulating the cell cycle. The disruption of protein kinase activity is intricately linked to pathways in tumor development. This manuscript explores the transformative impact of protein kinase inhibitors on cancer therapy, particularly their efficacy in cases driven by targeted mutations. Focusing on key tyrosine kinase inhibitors (TKIs) like Bcr-Abl, Epidermal Growth Factor Receptor (EGFR), and Vascular Endothelial Growth Factor Receptor (VEGFR), it targets critical kinase families in cancer progression...

Cancer metastasis is the primary cause of cancer deaths. Metastasis involves the spread of cancer cells from the primary tumors to other body parts, commonly through lymphatic and vascular pathways. Key aspects include the high mutation rate and the capability of metastatic cells to form invasive tumors even without a large initial tumor mass. Particular emphasis is given to early metastasis, occurring in initial cancer stages and often leading to misdiagnosis, which adversely affects survival and prognosis...

Pancreatic cancer (PC) is an immunosuppressive cancer. Immune-based therapies that enhance or recruit antitumor immune cells into the tumor microenvironment (TME) remain promising strategies for PC treatment. Consequently, a deeper understanding of the molecular mechanisms involved in PC immune suppression is critical for developing immune-based therapies to improve survival rates. In this study, weighted gene co-expression network analysis (WGCNA) was used to identify Filamin B (FLNB) correlated with the infiltration of CD8+ T cells and tumor-associated macrophages (TAMs)...

INTRODUCTION: Despite aggressive standard-of-care therapy, including surgery, radiation, and chemotherapy, glioblastoma recurrence is almost inevitable and uniformly lethal. Activation of glioma-intrinsic Wnt/β-catenin signaling is associated with a poor prognosis and the proliferation of glioma stem-like cells, leading to malignant transformation and tumor progression. Impressive results in a subset of cancers have been obtained using immunotherapies including anti-CTLA4, anti-PD-1, and anti-PD-L1 or chimeric antigen receptor (CAR) T cell therapies...

INTRODUCTION: Nuclear envelope spectrin repeat protein (Nesprin) 1 encoded by SYNE1, crucially regulates the morphology and functions of the cell. Mutations in the SYNE1 gene are associated with various diseases; however, their significance in renal cell carcinoma (RCC) remains unknown. In this study, we have investigated the association of SYNE1/Nesprin1 with the progression and prognosis of clear cell RCC (ccRCC). METHODS: In silico analyses of publicly available datasets of patients with RCC were performed...

Clinical pancreatic ductal adenocarcinoma (PDAC) treatment is severely limited by lack of effective KRAS suppression strategies. To address this dilemma, a reactive oxygen species (ROS)-responsive and PDAC-targeted nanodrug named Z/B-PLS was constructed to confront KRAS through dual-blockade of its downstream PI3K/AKT/mTOR and RAF/MEK/ERK for enhanced PDAC treatment. Specifically, photosensitizer zinc phthalocyanine (ZnPc) and PI3K/mTOR inhibitor BEZ235 (BEZ) were co-loaded into PLS which was constructed by click chemistry conjugating MEK inhibitor selumetinib (SEL) to low molecular weight heparin with ROS-responsive oxalate bond...

Background Colorectal cancer (CRC) is a significant global health challenge with high mortality rates. Dysregulation of β-catenin, epithelial-mesenchymal transition (EMT), and adenomatous polyposis coli (APC) are crucial in CRC development. Mutations in the APC gene lead to aberrant β-catenin expression, a key player in CRC pathogenesis. β-catenin not only influences canonical Wnt signaling but also regulates EMT. This study investigated the correlation between APC mutations, β-catenin dysregulation, and EMT induction in CRC...

PURPOSE: Cell-free circulating tumor DNA (ctDNA) has shown its potential as a quantitative biomarker for longitudinal monitoring of response to anticancer therapies. However, ctDNA dynamics have not been studied in patients with heavily pretreated, advanced solid tumors, for whom therapeutic responses can be weak. We investigated whether changes in ctDNA could predict clinical outcomes in such a cohort treated with combined poly(ADP-ribose) polymerase/vascular endothelial growth factor receptor inhibitor therapy...

To explore the relationship between quantitative perfusion histogram parameters of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) with the expression of tumor tissue epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and EGFR gene mutations in non-small cell lung cancer (NSCLC). A total of 44 consecutive patients with known NSCLC were recruited from March 2018 to August 2021. Histogram parameters (mean, uniformity, skewness, energy, kurtosis, entropy, percentile) of each (Ktrans , Kep , Ve , Vp , Fp ) were obtained by Omni Kinetics software...

The orbital manifestation of a solitary fibrous tumor (SFT) is exceptionally rare and poses specific challenges in diagnosis and treatment. Its rather exceptional behavior among all SFTs comprises a high tendency towards local recurrence, but it rarely culminates in metastatic disease. This raises the question of prognostic factors in orbital SFTs (oSFTs). Telomerase reverse transcriptase ( TERT )-promoter mutations have previously been linked to an unfavorable prognosis in SFTs of other locations. We analyzed the prevalence of TERT promoter mutations of SFTs in the orbital compartment...

The lymphatic system, crucial for tissue fluid balance and immune surveillance, can be severely impacted by disorders that hinder its activities. Lymphatic malformations (LMs) are caused by fluid accumulation in tissues owing to defects in lymphatic channel formation, the obstruction of lymphatic vessels or injury to lymphatic tissues. Somatic mutations, varying in symptoms based on lesions' location and size, provide insights into their molecular pathogenesis by identifying LMs' genetic causes. In this review, we collected the most recent findings about the role of genetic and inflammatory biomarkers in LMs that control the formation of these malformations...

Metastatic colorectal cancer remains a deadly malignancy and is the third leading cause of cancer-related death. The mainstay of treatment for metastatic colorectal cancer is chemotherapy, but unfortunately, even with recent progress, overall survival is still poor. Colorectal cancer is a heterogeneous disease, and the underlying genetic differences among tumors can define the behavior and prognosis of the disease. Given the limitations of cytotoxic chemotherapy, research has focused on developing targeted therapy based on molecular subtyping...

Vascular malformations are congenital lesions that occur due to mutations in major cellular signalling pathways which govern angiogenesis, cell proliferation, motility, and cell death. These pathways have been widely studied in oncology and are substrates for various small molecule inhibitors. Given their common molecular biology, there is now a potential to repurpose these cancer drugs for vascular malformation care; however, a molecular diagnosis is required in order to tailour specific drugs to the individual patient's mutational profile...

PURPOSE: This first-in-human phase I dose-escalation study evaluated the safety, pharmacokinetics, and efficacy of tinengotinib (TT-00420), a multi-kinase inhibitor targeting fibroblast growth factor receptors 1-3 (FGFRs 1-3), Janus kinase 1/2, vascular endothelial growth factor receptors, and Aurora A/B, in patients with advanced solid tumors. PATIENTS AND METHODS: Patients received tinengotinib orally daily in 28-day cycles. Dose escalation was guided by Bayesian modeling using escalation with overdose control...

Objective: To investigate the detection rate and metastasis rate of delphain lymph node （DLN）in thyroid papillary adenocarcinoma（PTC） and to analyze the risk factors for DLN metastasis. Methods: The clinicopathological data of 200 PTC patients admitted to the from January 2018 to June 2020 were retrospectively analyzed, and the detection of DLN was clearly recorded in the pathological reports of all patients. The number of DLN detected, the number of metastasis, the detection rate and the metastasis rate were counted...

BACKGROUND: A recently hypothesized cause of cell death called disulfidptosis has been linked to the expansion, emigration, and vascular rebuilding of cancer cells. Cancer can be treated by targeting the pathways that trigger cell death. AIM: To discover the long non-coding RNA of the disulfidaptosis-related lncRNAs (DRLs), prognosis clinical survival, and treat patients with colorectal cancer with medications. METHODS: Initially, we queried the Cancer Genome Atlas database to collect transcriptome, clinical, and genetic mutation data for colorectal cancer (CRC)...

Cytosine modifications at the 5-carbon position play a critical role in gene expression regulation and have been implicated in cancer development. 5-Hydroxymethylcytosine (5hmC), arising from 5-methylcytosine (5-mC) oxidation, has shown promise as a potential malignancy marker due to its depletion in various human cancers. However, its significance in thyroid tumors remains underexplored, primarily due to limited data. In our study, we evaluated 5hmC expression levels by immunohistochemistry in a cohort of 318 thyroid tumors...

Natural substances are strategic candidates for drug development in cancer research. Marine-derived molecules are of special interest due to their wide range of biological activities and sustainable large-scale production. Melanoma is a type of skin cancer that originates from genetic mutations in melanocytes. BRAF, RAS, and NF1 mutations are described as the major melanoma drivers, but approximately 20% of patients lack these mutations and are included in the triple wild-type (tripleWT) classification. Recent advances in targeted therapy directed at driver mutations along with immunotherapy have only partially improved patients' overall survival, and consequently, melanoma remains deadly when in advanced stages...

PURPOSE: Vascular anomalies are classified as either vascular tumors or vascular malformations. Vascular malformations can be difficult to diagnose and treat in the pediatric population and can masquerade as malignant processes. Understanding the genetics behind vascular malformations can lead to identification of specific mutations which can be treated with targeted immunotherapy. METHODS: Our case presents a pediatric patient with progressively enlarging vascular malformation despite multiple surgical resections and systemic medical treatments who underwent genetic evaluation and was found to have PIK3CA mutation...

INTRODUCTION: Tall cell carcinoma with reversed polarity (TCCRP) is a rare histologic subtype of breast cancer that was newly categorized in 2020. TCCRP is a relatively novel tumor, and there are no detailed reports about its cellular morphology. We were able to obtain imprint cytological specimens from fresh TCCRP tissue, and we provide our detailed observations. CASE PRESENTATION: The patient was a 73-year-old Japanese female with a 15-mm mass in her right breast...