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Background: Today, breast cancer is the most diagnosed cancer worldwide. There are many different clinical presentations, radiological characteristics, and histological types of breast cancer. HER2 is overexpressed in a significant number of breast cancer cases reaching 20% of all breast cancers, and its overexpression is seen directly proportionate with a poor outcome and prognosis. Methods: We started this cross-sectional research from January 2022–December 2023 on 202 breast cancer patients who had 220 lesions. The molecular subtypes of the different lesions were determined in all the included cases. Magnetic resonance imaging (MRI) studies were conducted in all included cases. The MRI parameters included conventional MRI, diffusion-weighted analysis, and dynamic post-contrast T1-weighted imaging. Results: The prevalence of irregular margins (P < 0.001), linear and segmental distribution (P = 0.044), heterogeneous pattern (P < 0.001), and type 2 curve was statistically significantly higher in the HER2-positive lesions. Nipple infiltration incidence showed statistically significant elevation in the HER2-positive lesions (P = 0.017). The lesions' ADC and perilesional ADC in the HER2-positive lesions were also statistically significantly elevated. The best cutoff point of ADC to detect lesions with positive HER2 expression was > 0.885 × 10–3 mm2/s, with 65.7% sensitivity and 60% specificity, with a statistically significant value (p = 0.005). Conclusions: Magnetic resonance imaging of breast imaging is a promising noninvasive method for identifying breast tumors with the HER2 molecular subtype. Combining various radiological features by MRI may provide a conclusion for recognizing positive HER2 lesions. [ABSTRACT FROM AUTHOR]

Background and objective Isoliquiritigenin (ISL) is an important pharmacological constituent of Glycyrrhiza glabra, which possesses a range of physiological and pharmacological activities, as well as significant antitumor activity, and can be used as a potential drug for targeted cancer therapy. LINC01503 is an oncogene, which has been closely associated with the malignant biological processes of many cancers. The aim of this study was to investigate the effects of ISL on the proliferation, apoptosis, invasion and migration of lung squamous carcinoma cells by regulating LINC01503. Methods Plasma was collected from lung squamous carcinoma patients and healthy individuals treated at Tangshan People's Hospital from January 2021 to December 2022. The expression of LINC01503 in lung squamous carcinoma plasma, tissues and cells was detected by real-time quantitative fluorescence polymerase chain reaction (qRT-PCR). Lung squamous carcinoma cells were treated with different concentrations of ISL for 24 h, and LINC01503 expression was detected by qRT-PCR. The cells were treated in groups: si-NC group, si-LINC01503 group, DMSO (0.1% dimethyl sulfone) group, ISL group, pc DNA3.1(+)-NC group, pc DNA3.1(+)-LINC01503 group, ISL+pc DNA3.1(+)-NC group and ISL+pc DNA3.1(+)- LINC01503 groups. CCK-8 assay, clone formation assay, flow cytometry, Transwell assay and scratch assay were used to explore the effect of LINC01503 on the functional phenotype of lung squamous carcinoma cells. Results Fluorescence in situ hybridization results showed that the average fluorescence intensity of LINC01503 in tissue microarrays of lung squamous carcinoma patients was higher than that in paracancerous tissues (P<0.05). The expression of LINC01503 in the plasma of patients with lung squamous carcinoma was higher than that in the plasma of healthy individuals (P<0.05). Knockdown of LINC01503 inhibited the proliferation, invasion and migration of lung squamous carcinoma cells and promoted apoptosis (P<0.05). ISL inhibited the proliferation, invasion, migration and promoted apoptosis of lung squamous carcinoma cells (P<0.05). Overexpression of LINC01503 followed by intervention with ISL reversed the promotional effect of overexpression of LINC01503 on the proliferation, invasion and migration of lung squamous carcinoma cells as well as the inhibitory effect on apoptosis (P<0.05). Conclusion LINC01503 was highly expressed in lung squamous carcinoma, and LINC01503 could promote the proliferation, invasion and migration of lung squamous carcinoma cells and inhibit the apoptosis, ISL could inhibit the proliferation, invasion and migration of lung squamous carcinoma cells and promote apoptosis of lung squamous carcinoma cells by regulating the expression of LINC01503. [ABSTRACT FROM AUTHOR]

Multiple primary lung cancer (MPLC) refers to patients with two or more primary lesions of lung cancer. It can be divided into synchronous MPLC (sMPLC) and metachronous MPLC (mMPLC) based on the timing of occurrence. In recent years, the detection rate of MPLC has gradually increased. However, considerable controversy exists in distinguishing MPLC from intrapulmonary metastasis (IM), especially when the histopathological types are identical. Given the significant differences in treatment strategies and prognosis in clinical practice currently, accurate diagnosis of MPLC is crucial for personalized precision therapy. Molecular genetics and sequencing technologies offer effective strategies for assessing the clonal origin of tumors. There have been reports of coexisting mutations in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) fusion genes in non-small cell lung cancer, but case of EGFR mutation following an ALK mutation has not been mentioned. This article accurately diagnoses and retrospectively analyzes the clinical data of a case of ALK mutant adenocarcinoma in a male patient who developed an EGFR mutation with multiple metastases four years after surgery, and reviews the relevant literature. This paper aims to deepen the understanding of mMPLC and provide clinical references for the diagnosis and treatment of such patients. [ABSTRACT FROM AUTHOR]

Lung cancer is the most common malignant disease and the leading cause of cancer death in China. Non-small cell lung cancer (NSCLC) accounts for over 80% of all lung cancers, and the probability of NSCLC gene mutations is high, with a wide variety of types. With the development of next-generation sequencing (NGS) detection technology, more and more patients with rare fusion gene mutations are detected. Neuregulin 1 (NRG1) gene is a rare oncogenic driver that can lead to activation of human epidermal growth factor receptor 3 (Her3/ErbB3) mediated pathway, resulting in tumor formation. In this article, we reported a case of mixed NSCLC with CRISPLD2-NRG1 fusion detected by RNA-based NGS, who responsed to Afatinib well after 1 month of treatment, and magnetic resonance imaging (MRI) showed shrinkage of intracranial lesions. Meanwhile, we also compiled previously reported NSCLC patients with NRG1 rare gene fusion mutation, in order to provide effective references for clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Lung cancer is still the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) is the main pathological type of lung cancer, accounting for about 80%. Approximately 30% of all patients with NSCLC have resectable early and middle stage disease at the time of diagnosis. Recently, the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have made a major breakthrough in the adjuvant targeted therapy of EGFR-mutated resectable NSCLC, and are recommended by the guidelines for clinical use. In this review, we summarize the clinical research progress of perioperative adjuvant targeted therapy for EGFR-mutated resectable NSCLC, and discuss the key issues in the clinical researches. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the expression of EGFR and HER-2 oncogenes using an experimental two stage chemically induced carcinogenesis protocol on the dorsal skin in FVB/N mice. Forty female FVB/N mice 4 weeks old, were grouped into one control (n = 8) and two experimental groups (Group A: n = 16, Group B: n = 16) following a randomization process. Two-stage carcinogenesis protocol, was implicated, including an initial treatment with 97.4 nmol DMBA on their shaved dorsal skin and subsequent treatments of 32.4 nmol TPA applications after 13 weeks for Group A and after 20 weeks for Group B. The control group C, received no treatment. Skin was examined weekly for tumor development. Post-experiment, animals were euthanized for tissue analysis. The histological status of the skin lesions in the experimental groups corresponded well with tumour advancement (from dysplasia to poorly-differentiated carcinoma). Tumour sections were evaluated histologically and immunohistochemically. EGFR expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 008 respectively), while tended to be higher in benign tumours (p = 079), compared to normal histology. Moreover, mean percentage of EGFR positive expression in malignant tumours was significantly higher than in benign tumours (p < 001). HER-2 expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 015 respectively), while tended to be higher in benign tumours (p = 085), compared to normal histology. Furthermore, mean percentage of HER-2 positive expression in malignant tumours was significantly higher than in benign tumours (p = 005). The study demonstrated that in FVB/N mice subjected to a two-stage chemically induced carcinogenesis protocol, there was a significant increase in the expression of EGFR and HER-2 oncogenes in precancerous and malignant skin lesions compared to normal tissue. This suggests a potentially early role of these oncogenes in the progression of skin tumours in this model. [ABSTRACT FROM AUTHOR]

V-Raf murine sarcoma viral oncogene homolog B (BRAF) alteration is one of the most essential driver genes of non-small cell lung cancer (NSCLC). BRAF encodes serine/threonine protein kinases, and its mutations typically lead to protein compositional activation, thereby activating the mitogen-activated protein kinase kinase (MEK) signaling pathway. A promising new approach for the treatment of mutated BRAF and/or downstream MEK may provide customized treatment opportunities for BRAF driven NSCLC patients. However, combination therapy is necessary to overcome the difficulties such as short duration of benefit, poor therapeutic effect of non-V600 BRAF mutations and susceptibility to drug resistance. This article reviewed the progress in structural characteristics, related signaling pathways, mutation types of BRAF gene, and the clinical pathological relationship between BRAF mutations and NSCLC, as well as the therapy, in order to provide more evidences for clinical doctors to make treatment decisions. [ABSTRACT FROM AUTHOR]

Background and objective Transcription factor (TF) can bind specific sequences that either promotes or represses the transcription of target genes, and exerts important effects on tumorigenesis, migration, invasion. Staphylococcal nuclease-containing structural domain 1 (SND1), which is a transcriptional co-activator, is considered as a promising target for tumor therapy. However, its role in lung adenocarcinoma (LUAD) remains unclear. This study aims to explore the role of SND1 in LUAD. Methods Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) database was obtained to explore the association between SND1 and the prognosis, as well as the immune cell infiltration, and subcellular localization in LUAD tissues. Furthermore, the functional role of SND1 in LUAD was verified in vitro. EdU assay, CCK-8 assay, flow cytometry, scratch assay, Transwell assay and Western blot were performed. Results SND1 was found to be upregulated and high expression of SND1 is correlated with poor prognosis of LUAD patients. In addition, SND1 was predominantly present in the cytoplasm of LUAD cells. Enrichment analysis showed that SND1 was closely associated with the cell cycle, as well as DNA replication, and chromosome segregation. Immune infiltration analysis showed that SND1 was closely associated with various immune cell populations, including T cells, B cells, cytotoxic cells and dendritic cells. In vitro studies demonstrated that silencing of SND1 inhibited cell proliferation, invasion and migration of LUAD cells. Besides, cell cycle was blocked at G1 phase by down-regulating SND1. Conclusion SND1 might be an important prognostic biomarker of LUAD and may promote LUAD cells proliferation and migration. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the malignant tumors with the highest incidence and mortality rate in China, and its occurrence and development mechanism and treatment methods are the current research focuses. In recent years, the emergence of drugs targeting various tumor driver genes has significantly improved patients' survival and quality of life, setting off a wave of research on new therapeutic targets. Among them, long non-coding RNA (lncRNA) plays a crucial role in the malignant behavior of tumors, which has attracted widespread attention. Shown by a large number of studies, partial members of lncRNA small nucleolar RNA host gene (SNHG) family are aberrantly expressed in many maliglant tumors including non-small cell lung cancer (NSCLC) and participate in cell proliferation, invasion and migration, which may act as a new diagnostic and prognostic biomarker and can be a therapeutic target of NSCLC. In this review, we comprehensively summarize and explore the recent investigation of SNHGs in NSCLC in order to provide new ideas for the diagnosis and treatment of NSCLC [ABSTRACT FROM AUTHOR]

Ras homolog gene family member V (RHOV) is an atypical Rho GTPase that participates in various important cellular processes. Although RHOV has been identified to play an oncogenic role in lung cancer and triple‐negative breast cancer, its role in other types of tumors remains unknown. In this study, we investigated the expression of RHOV in pan‐cancer analysis using The Cancer Genome Atlas (TCGA) and Gene‐Tissue Expression datasets. RHOV mRNA levels were dysregulated in several types of tumors. RHOV expression was identified as an independent prognostic factor in 7 of 33 types of tumors; however, the relationship varied according to tumor type. Higher RHOV expression was associated with a favorable prognosis in kidney renal cell carcinoma and prostate adenocarcinoma, for which RHOV expression was downregulated, whereas RHOV expression was associated with a poor prognosis for patients with adenoid cystic carcinoma, lung adenocarcinoma, pancreatic ductal adenocarcinoma, skin cutaneous melanoma, and uveal melanoma with upregulated RHOV expression. Furthermore, RHOV expression was associated with various clinicopathological parameters in these tumors. RHOV expression showed varied associations with different types of tumor‐infiltrating immune cells and demonstrated a potential impact on the response to immunotherapy depending on the cancer type. Additionally, functional enrichment analysis of RHOV‐related genes demonstrated a role in a wide range of developmental and immune‐related processes. This study provides valuable insights into the role of RHOV in pan‐cancer development, indicating its role as a tumor suppressor or oncogene according to the cancer type and tumor microenvironment. [ABSTRACT FROM AUTHOR]

In advanced non-small cell lung cancer (NSCLC), V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation is highly malignant and has poor prognosis, and currently Dabrafenib in combination with Trametinib is approved for first-line treatment of patients with BRAF V600 mutation. In addition to mutations, BRAF fusion can also occur. With the development of gene detection, the detection of BRAF fusion is gradually increasing, but there is a lack of effective therapeutic strategies for BRAF fusion. In this paper, we review the clinical characteristics, mechanism of action, and clinical treatment of BRAF fusion to provide a basis for the treatment of BRAF fusion in NSCLC patients. [ABSTRACT FROM AUTHOR]

Oncogene E6 plays a critical role in the development and progression of esophageal cancer caused by human papillomavirus (HPV) infection. Alpha‐ketoglutarate (AKG) is a key metabolite in the tricarboxylic acid cycle and has been widely used as a dietary and anti‐ageing supplement. In this study, we found that treating esophageal squamous carcinoma cells with a high dose of AKG can induce cell pyroptosis. Furthermore, our research confirms that HPV18 E6 inhibits AKG‐induced pyroptosis of esophageal squamous carcinoma cells by lowering P53 expression. P53 downregulates malate dehydrogenase 1 (MDH1) expression; however, MDH1 downregulates L‐2‐hydroxyglutarate (L‐2HG) expression, which inhibits a rise in reactive oxygen species (ROS) levels—as L‐2HG is responsible for excessive ROS. This study reveals the actuating mechanism behind cell pyroptosis of esophageal squamous carcinoma cells induced by high concentrations of AKG, and we posit the molecular pathway via which the HPV E6 oncoprotein inhibits cell pyroptosis. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPVs) infect epithelial cells of human beings, and their replication cycle is associated with epithelial differentiation. More than 200 genotypes of HPVs were identified, and each of these HPVs shows distinct specificity for tissues and infection. HPV infection was involved in the development of lesions on the feet, genital warts and hands. The evidence of HPV infection revealed the role of HPVs in neck and head squamous cell carcinoma, esophageal cancer, cervical cancer, head and neck cancer, brain and lung tumours. The independent traditional risk factors, various clinical outcomes, and increased prevalence among certain populations and geographical regions have led increasing interest in HPV infection. The mode of HPVs transmission remains unclear. Moreover, in recent years, vertical transmission of HPVs was reported. This review concludes present knowledge about HPV infection, virulence strains, clinical significance of HPVs, and mode of transmission, and vaccination strategies. [ABSTRACT FROM AUTHOR]

Secretory carcinoma (SC) is a salivary gland neoplasm included in the latest World Health Organization Classification of Head and Neck Tumours. Its morphologic and immuno-histochemical characteristics resemble those of breast secretory carcinoma, and the tumors share the same fusion gene, ETV6::NTRK3. This chromosome translocation can be confirmed through reverse transcription-polymerase chain reaction or located using ETV6 fluorescent in situ hybridization. These techniques are expensive, and few laboratories can carry out molecularanalysis. In addition, some of these tumors are related to non-NTRK fusion types and non-ETV6 translocation. Therefore, recognition of the typical histopathologic features of SC is the first step in considering this disease among the diagnostic hypotheses. In this case series, morphologic findings combined with immunohistochemical profiles were sufficient to make the correct diagnosis. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor exon 20 insertion (EGFR ex20ins) is one of the earliest driver gene activation mutations in non-small cell lung cancer (NSCLC). However, due to the unique structure of protein variation caused by this mutation, most patients with EGFR ex20ins mutation (except A763_Y764insFQEA) have poor response to the launched first/ second/third generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). With the successive approval of new specific targeted drugs for EGFR ex20ins in Food and Drug Administration (FDA) and other national regulatory agencies, the development and clinical research of targeted drugs for EGFR ex20ins in China have also developed rapidly and Mobocertinib has been approved recently in China. It is worth noting that EGFR ex20ins is a variant type with strong molecular heterogeneity. How to detect it comprehensively and accurately in clinical practice, so as to enable more patients to benefit from targeted therapy, is a very important and urgent problem to be solved. This review introduces the molecular typing of EGFR ex20ins, then discusses the importance of EGFR ex20ins detection and the differences of various detection methods, and summarizes the research and development of new drugs progress of EGFR ex20ins, in order to optimize the diagnosis and treatment path of EGFR ex20ins patients by selecting accurate, rapid and appropriate detection methods, so as to improve the clinical benefits of the patients. [ABSTRACT FROM AUTHOR]

to explore the value of T1ρ mapping in preoperatively predicting the status of ER, PR, HER-2 and Ki-67 in patients with breast cancer 26 biopsy proved breast cancer patients were prospectively enrolled in this study. They all received preoperative clinical routine breast MRI and T1 ρ mapping sequence. Patients were grouped into ER, PR, Her-2 and Ki-67 negative (n=5, 5, 20, 13, respectively) and positive groups (n=21, 21, 6, 13, respectively) with reference to pathological results. ROIs were drawn by two radiologists along the edge of the tumor at three largest slices on T1ρ mapping images, and avoiding artifacts, blood vessels, necrosis, etc. Calculate the average value of two measurements as a final absolute T1ρ value of the lesion. Independent t test, ROC curves, analysis were used for statistical analyses. Patients with ER positive status had significantly lower T1ρ value than negative group (P<0.01). ROC curve showed that T1p presented AUCs of 0.867 in predicting ER status. Patients with PR positive status also had significantly lower T1ρ value than negative group (P=0.01). ROC curve showed that T1p presented AUCs of 0.79 in predicting PR status. Patients with Her-2 positive status had significantly higher T1ρ value than negative group (P=0.04). ROC curve showed that T1p presented AUCs of 0.77 in predicting Her-2 status. Patients with Ki-67 positive status showed significantly higher T1ρ value than negative group (P=0.02). ROC curve showed that T1p presented AUCs of 0.75 in predicting Ki-67 status. T1ρ Mapping has the potential for preoperative evaluation of ER, PR, HER-2, and Ki-67 status, which may give additional information to guide individualized therapeutic strategy in breast cancer. [ABSTRACT FROM AUTHOR]

Sinonasal squamous cell carcinoma (SNSCC) is one of the least frequent carcinomas in the head and neck and accounts for 60% to 75% of sinonasal malignancies. The role of long non-coding RNAs (lncRNAs) in cancer development has drawn great attention over the years. The current study intended to assess the role and specific mechanism of lncRNA double homeobox A pseudogene 8 (DUXAP8) in SNSCC. Quantitative real-time PCR (qRT-PCR) analysis was implemented to assess the expression level of DUXAP8, microRNA-584-5p (miR-584-5p), and fibronectin type III domain containing 3B (FNDC3B). Proliferation assays included colony formation assay, Cell Counting Kit-8 (CCK-8) assay, and 5-ethynyl-2′-deoxyuridine (EdU) assay. Transwell assays were implemented to monitor cell migration and invasion. Cell apoptosis was evaluated via terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) and JC-1 experiments. Mechanism experiments included RNA pull-down assay, RNA binding protein immunoprecipitation (RIP) assay, and luciferase reporter assay. DUXAP8 is overexpressed in SNSCC cells. Functionally, DUXAP8 silencing suppresses the malignant progression of SNSCC. Furthermore, DUXAP8 up-regulates the expression of FNDC3B via sponging miR-584-5p. Rescue experiments demonstrated that DUXAP8 mediates the progression of SNSCC via up-regulating FNDC3B expression. In conclusion, DUXAP8 acts as an oncogene in SNSCC, which may be a new molecular marker for SNSCC. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Single-cell transcriptome sequencing (scRNA-seq) can provide accurate gene expression data for individual cells. In this study, a new prognostic model was constructed by scRNA-seq and bulk transcriptome sequencing (bulk RNA-seq) data of CRC samples to develop a new understanding of CRC. Methods: CRC scRNA-seq data were downloaded from the GSE161277 database, and CRC bulk RNA-seq data were downloaded from the TCGA and GSE17537 databases. The cells were clustered by the FindNeighbors and FindClusters functions in scRNA-seq data. CIBERSORTx was applied to detect the abundance of cell clusters in the bulk RNA-seq expression matrix. WGCNA was performed with the expression profiles to construct the gene coexpression networks of TCGA-CRC. Next, we used a tenfold cross test to construct the model and a nomogram to assess the independence of the model for clinical application. Finally, we examined the expression of the unreported model genes by qPCR and immunohistochemistry. A clone formation assay and orthotopic colorectal tumour model were applied to detect the regulatory roles of unreported model genes. Results: A total of 43,851 cells were included after quality control, and 20 cell clusters were classified by the FindCluster () function. We found that the abundances of C1, C2, C4, C5, C15, C16 and C19 were high and the abundances of C7, C10, C11, C13, C14 and C17 were low in CRC tumour tissues. Meanwhile, the results of survival analysis showed that high abundances of C4, C11 and C13 and low abundances of C5 and C14 were associated with better survival. The WGCNA results showed that the red module was most related to the tumour and the C14 cluster, which contains 615 genes. Lasso Cox regression analysis revealed 8 genes (PBXIP1, MPMZ, SCARA3, INA, ILK, MPP2, L1CAM and FLNA), which were chosen to construct a risk model. In the model, the risk score features had the greatest impact on survival prediction, indicating that the 8-gene risk model can better predict prognosis. qPCR and immunohistochemistry analysis showed that the expression levels of MPZ, SCARA3, MPP2 and PBXIP1 were high in CRC tissues. The functional experiment results indicated that MPZ, SCARA3, MPP2 and PBXIP1 could promote the colony formation ability of CRC cells in vitro and tumorigenicity in vivo. Conclusions: We constructed a risk model to predict the prognosis of CRC patients based on scRNA-seq and bulk RNA-seq data, which could be used for clinical application. We also identified 4 previously unreported model genes (MPZ, SCARA3, MPP2 and PBXIP1) as novel oncogenes in CRC. These results suggest that this model could potentially be used to evaluate the prognostic risk and provide potential therapeutic targets for CRC patients. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Lung Cancer is the property of Chinese Journal of Lung Cancer and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Mesenchymal-epithelial transition factor (MET) amplification is an important driver of resistance in epidermal growth factor receptor (EGFR) -mutant non-small cell lung cancer (NSCLC), and the combination of MET proto-oncogene (MET) and EGFR-tyrosine kinase inhibitors (TKIs) has shown promise in overcoming this molecularly defined acquired resistance. Emerging data also demonstrate MET amplification as a resistance driver to TKIs-treated anaplastic lymphoma kinase (ALK)-, RET-, and ROSI-fusion NSCLC. Here, we review the literature on recent research progress of MET amplification as a resistance driver to targeted therapy in oncogene-driven NSCLC and summarize the progress of clinical strategies to overcome the resistance mechanism. [ABSTRACT FROM AUTHOR]

Proteolysis targeting chimeria (PROTAC) degrades target proteins by utilizing the ubiquitin-proteasome pathway, subverting the concept of traditional small molecule inhibitors. Among the common mutation targets of non-small cell lung cancer (NSCLC), PROTAC technology has successfully achieved the effective degradation of kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK ) and other proteins in preclinical studies. PROTAC drugs with their unique event-driven advantages, are expected to overcome acquired drug resistance caused by small molecule inhibitors and show good therapeutic potential for undruggable targets, thereby providing a new strategy for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the role of ELF3, an ETS family member in normal prostate growth and prostate cancer. Silencing ELF3 in both benign prostate (BPH-1) and prostate cancer (PC3) cell lines resulted in decreased colony-forming ability, inhibition of cell migration and reduced cell viability due to cell cycle arrest, establishing ELF3 as a cell cycle regulator. Increased ELF3 expression in more advanced prostate tumours was shown by immunostaining of tissue microarrays and from analysis of gene expression and genetic alteration studies. This study indicates that ELF3 functions not only as a part of normal prostate epithelial growth but also as a potential oncogene in advanced prostate cancers. [ABSTRACT FROM AUTHOR]

Background and objective Reticulosome family gene 1 (RTN1) is a reticulosome-encoding gene associated with the endoplasmic reticulum. RTN1 plays a key role in membrane trafficking or neuroendocrine secretion of neuroendocrine cells, while RTN1 serves as a potential diagnostic/therapeutic marker for neurological diseases and cancer. However, the expression of RTN1 and its effect on the immune microenvironment in patients with lung adenocarcinoma have not been reported. In this study, we aimed to investigate the expression of RTN1 in lung adenocarcinoma and its correlation with immune infiltration and survival in lung adenocarcinoma using public databases and bioinformatics network tools. Methods Expression levels of RTN1 mRNA in tumor and normal tissues were analyzed using Tumor Immune Estimation Resource 2.0 (TIMER 2.0) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2). RTN1 protein expression was examined using the Human Protein Atlas. The clinical prognostic significance of RTN1 was analyzed using the GEPIA2 plotter database. To further confirm the potential function of RTN1, the data were analyzed using gene set enrichment analysis. In addition, We performed dimensionality-reduced clustering analysis at the single-cell sequencing level on two datasets from the Tumor Immune Single-cell Hub (TISCH) database to observe the cellular clustering of RTN1 in different types of immune cells. Using the TIMER online tool to analyze and predict the infiltration abundance of different types of immune cells in the immune microenvironment of lung adenocarcinoma patients in the TCGA cohort; TIMER and CIBERSORT were used to study the relationship between genes co-expressed with RTN1 and its associated tumor-infiltrating immune cells; finally, TIMER was used to analyze the relationship between RTN1 and immune correlations between immune checkpoints. Results We found that RTN1 expression was decreased in patients with lung adenocarcinoma and was closely related to patient prognosis. RTN1 is involved in the process of phagosome formation, hematopoietic cell formation and cell adhesion, and plays an important role in T cell activation. Using cBioPortal and TCGA data to analyze, it is found that RTN1 is significantly associated with BTK, CD4, ECSF1R, MNDA, NCIKAP1L and SNX20. High expression of the above genes may cause significant upregulation of CD4+ T cells, mast cells, monocytes, myeloid dendritic cells and M1 macrophages. The expression of RTN1 is closely related to the common immune checkpoints CD274, CTLA4, HAVCR2, LAG3, PDCD1, PDCD1LG2, TIGIT and SIGLEC15 immune checkpoints. Conclusion RTN1 may act as a tumor suppressor gene and indicate better prognosis. Furthermore, RTN1 is associated with immune infiltration that may be involved in the immunotherapy response in LUAD. However, the related mechanism needs further research. [ABSTRACT FROM AUTHOR]

NSCLC has a diverse genomic background with mutations in key proto-oncogenic drivers including Kirsten rat sarcoma (KRAS) and epidermal growth factor receptor (EGFR). Roughly 40% of adenocarcinoma harbor Kras activating mutations regardless of smoking history. Most KRAS mutations are located at G12, which include G12C (roughly 40%), G12V (roughly 20%), and G12D (roughly 15%). KRAS mutated NSCLC have higher tumor mutational burden and some have increased PD-1 expression, which has resulted in better responses to immunotherapy than other oncogenes. While initial treatment for metastatic NSCLC still relies on chemo-immunotherapy, directly targeting KRAS has proven to be efficacious in treating patients with KRAS mutated metastatic NSCLC. To date, two G12C inhibitors have been FDA-approved, namely sotorasib and adagrasib. In this review, we summarize the different drug combinations used to target KRAS G12c, upcoming G12D inhibitors and novel therapies targeting KRAS. [ABSTRACT FROM AUTHOR]

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

With the rapid development and wide application of next generation sequencing (NGS) technology, a series of researches have revealed that concurrent genetic alterations play an important role in the response and resistance of epidermal growth factor receptor (EGFR)-mutant NSCLC to EGFR-tyrosine kinase inhibitor (TKI). Besides, TP53 mutation is the most common co-mutation gene in EGFR-mutant NSCLC, which has been proved to confer a worse prognosis in EGFR- mutated patients treated with first, second and third generation of EGFR-TKIs. Currently, it is still being explored how to select the best treatment strategies for patients with concomitant presence of TP53 mutation in EGFR-mutant NSCLC. Here, we review the literature on recent research progress of TP53 concurrent mutation in EGFR-mutant advanced NSCLC. [ABSTRACT FROM AUTHOR]

Background: Myocardial ischemia reperfusion injury (MIRI) is an important mechanism of post-myocardial infarction injury and a main cause of death in patients with ischemic heart disease. Electroacupuncture (EA) pretreatment is effective for the prevention and treatment of MIRI, but mechanisms mediating the effects of cardiovascular disease EA treatments remain unclear. Objectives: To determine whether the lateral hypothalamus (LHA) and the cerebellar fastigial nucleus (FN) are involved in the protective effects of EA stimulation on MIRI. Methods: EA pretreatment was performed for 7 days before the establishment of the MIRI model. ST-segment changes on electrocardiograms were recorded and the Curtis-Walker arrhythmia score was used to evaluate changes in reperfusion injury. Hematoxylin-eosin staining was applied to evaluate the pathological and morphological changes in myocardial tissue. c-fos expression in the LHA and FN was determined by immunofluorescence staining. Glutamic (Glu) and γ-Aminobutyric acid (GABA) levels were measured using a high-performance liquid chromatography-electrochemical method. Results: EA pretreatment reduced ST-segment elevation, arrhythmia scores, and morphological changes in MIRI myocardial cells in rats, and decreased the c-fos protein expression in LHA/FN nuclei. MIRI was associated with an imbalance between GABA and Glu levels, whereas EA pretreatment increased GABA levels and decreased Glu levels in the LHA/FN. Conclusion: FN and LHA are involved in the EA-mediated attenuation of MIRI. Pretreatment with EA plays a protective role in the myocardium by regulating Glu and GABA release in the LHA and FN. [ABSTRACT FROM AUTHOR]

Osimertinib-induced interstitial lung disease (ILD) is an uncommon, but fatal pulmonary toxicity in some patients. We report a case of a 64-year-old male with stage IV adeno-non-small cell lung cancer (NSCLC) harboring an exon 19 deletion in the epidermal growth factor receptor (EGFR) treated with osimertinib 80 mg/d for first-line targeted therapy. On day 60 after initiating treatment of osimertinib, the patient developed ILD. Osimertinib was discontinued immediately and oral prednisone 60 mg/d was initiated, ILD improved within 13 d. After balancing the risk and benefit, osimertinib was restarted concurrently with prednisone. The patient showed neither disease progression nor a recurrence of ILD for more than 16 months. Based on our case and literature review, retreatment with osimertinib under steroid coverage could be considered as an effective treatment option after careful risk-benefit assessment for patients with EGFR-mutant NSCLC. [ABSTRACT FROM AUTHOR]

Abstract: Since the proof of concept of synthetic lethality between poly(ADP-ribose) polymerase inhibition and loss of BRCA1/2 homologous recombination (HR) function in preclinical models and early phase clinical trials, poly(ADP-ribose) polymerase inhibitors (PARPi) are increasing part of standard-of-care treatment for advanced breast cancers with BRCA gene mutations. The field has also recently seen benefits for PARPi in early breast cancer in those with germline BRCA1 and BRCA2 pathogenic mutations, and signals that synthetic lethal affects may occur in tumors with deficiencies in HR caused by germline, somatic, or epigenetic dysregulation of a number of HR genes. Despite the evidence of the synthetic lethal effects of PARPi, they are not always effective in HR defective cancers, and as they become part of standard of care in breast cancer, the study of prevalence of distinct mechanisms of resistance to PARPi and cross-resistance with other DNA-damaging agents such as platinum in breast cancer will be important and may inform therapy choices. [ABSTRACT FROM AUTHOR]

Cancer/Testis (CT) genes are induced in germ cells, repressed in somatic cells, and derepressed in somatic tumors, where these genes can contribute to cancer progression. CT gene identification requires data obtained using standardized protocols and technologies. This is a challenge because data for germ cells, gonads, normal somatic tissues, and a wide range of cancer samples stem from multiple sources and were generated over substantial periods of time. We carried out a GeneChip‐based RNA profiling analysis using our own data for testis and enriched germ cells, data for somatic cancers from the Expression Project for Oncology, and data for normal somatic tissues from the Gene Omnibus Repository. We identified 478 candidate loci that include known CT genes, numerous genes associated with oncogenic processes, and novel candidates that are not referenced in the Cancer/Testis Database (www.cta.lncc.br). We complemented RNA expression data at the protein level for SPESP1, GALNTL5, PDCL2, and C11orf42 using cancer tissue microarrays covering malignant tumors of breast, uterus, thyroid, and kidney, as well as published RNA profiling and immunohistochemical data provided by the Human Protein Atlas (www.proteinatlas.org). We report that combined RNA/tissue profiling identifies novel CT genes that may be of clinical interest as therapeutical targets or biomarkers. Our findings also highlight the challenges of detecting truly germ cell‐specific mRNAs and the proteins they encode in highly heterogenous testicular, somatic, and tumor tissues. [ABSTRACT FROM AUTHOR]

Synthetic lethality is a proven effective antitumor strategy that has attracted great attention. Large-scale screening has revealed many synthetic lethal genetic phenotypes, and relevant small-molecule drugs have also been implemented in clinical practice. Increasing evidence suggests that CDKs, constituting a kinase family predominantly involved in cell cycle control, are synthetic lethal factors when combined with certain oncogenes, such as MYC , TP53 , and RAS , which facilitate numerous antitumor treatment options based on CDK-related synthetic lethality. In this review, we focus on the synthetic lethal phenotype and mechanism related to CDKs and summarize the preclinical and clinical discoveries of CDK inhibitors to explore the prospect of CDK inhibitors as antitumor compounds for strategic synthesis lethality in the future. This review summarizes the CDKs-related synthetic lethality cases and the mechanisms, giving a guidance for drug combination antitumor strategies and tumor prediction by specific biomarkers. [Display omitted] [ABSTRACT FROM AUTHOR]

In the past 20 years, with the development of molecular biology, the treatment of non-small cell lung cancer (NSCLC) has been developing. Targeted therapy has improved the survival period of patients with positive mutation of tumor driver gene. More and more targets have been found gradually. Drugs targeting different driving genes have brought the treatment of NSCLC into a promising target era. Among the many driving genes of NSCLC, the fusion of transfection proto oncogene (RET) is the addition of the epidermal growth factor receptor (EGFR), analytic lymphama kinase (ALK) and c-ros oncogene 1-receptor tyrosine kinase (ROS1) are emerging targets. Targeted drugs for RET gene fusion have been constantly updated. Recently, new high selective RET inhibitors blu-667 and loxo-292 have made important breakthroughs. This paper will review the review of the fusion mutation of RET gene in NSCLC, the detection methods, clinicopathological characteristics, targeted treatment and the research progress after drug resistance. [ABSTRACT FROM AUTHOR]

Cancer cell dysregulations result in the abnormal regulation of cellular metabolic pathways. By simulating this metabolic reprogramming using constraint‐based modeling approaches, oncogenes can be predicted, and this knowledge can be used in prognosis and treatment. We introduced a trilevel optimization problem describing metabolic reprogramming for inferring oncogenes. First, this study used RNA‐Seq expression data of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) samples and their healthy counterparts to reconstruct tissue‐specific genome‐scale metabolic models and subsequently build the flux distribution pattern that provided a measure for the oncogene inference optimization problem for determining tumorigenesis. The platform detected 45 genes for LUAD and 84 genes for LUSC that lead to tumorigenesis. A high level of differentially expressed genes was not an essential factor for determining tumorigenesis. The platform indicated that pyruvate kinase (PKM), a well‐known oncogene with a low level of differential gene expression in LUAD and LUSC, had the highest fitness among the predicted oncogenes based on computation. By contrast, pyruvate kinase L/R (PKLR), an isozyme of PKM, had a high level of differential gene expression in both cancers. Phosphatidylserine synthase 1 (PTDSS1), an oncogene in LUAD, was inferred to have a low level of differential gene expression, and overexpression could significantly reduce survival probability. According to the factor analysis, PTDSS1 characteristics were close to those of the template, but they were unobvious in LUSC. Angiotensin‐converting enzyme 2 (ACE2) has recently garnered widespread interest as the SARS‐CoV‐2 virus receptor. Moreover, we determined that ACE2 is an oncogene of LUSC but not of LUAD. The platform developed in this study can identify oncogenes with low levels of differential expression and be used to identify potential therapeutic targets for cancer treatment. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor type 2 (HER2)-expressing breast cancer patients indicate poor prognosis in disease progression. HER2 overexpression can increase activities of Ras-mitogen activated protein kinase (Ras-MAPK) pathway and Janus Kinase (JAK)-STAT3, increasing breast cancer cell proliferation as demonstrated by marker Ki67. Therapeutic options for HER2-expressing breast cancer are limited and have major side effects, so anticancer development as an antiproliferative is needed. From previous research, synthetic chemical 4-(tert-butyl)-N-carbamoylbenzamide (4TBCB) compound has cytotoxic activity in vitro on HER2-expressing breast cancer cells. This study wanted to determine the mechanism 4TBCB compound in inhibiting HER2 signaling through Rat Sarcoma (Ras) and signal transducer and activator of transcription 3 (STAT3) pathway in HER2-expressing breast cancer cells. Breast cancer cells were isolated from the biopsy tissue of breast cancer patients. The isolated cells were cultured and given 4TBCB test compound with three concentrations (0.305, 0.61, and 1.22 mM) and lapatinib 0.05 mM as a comparison compound. Cancer cell cultures were stained with monoclonal antibodies phosphorylated HER2 (pHER2), phosphorylated Ras (pRas), phosphorylated STAT3 (pSTAT3), and Ki67. The expression of pHER2, pRas, pSTAT3, and Ki67 proteins was observed using the immunofluorescence method and the results were compared with control cells, namely cancer cells that were not given 4TBCB and lapatinib but stained with monoclonal antibodies. 4TBCB compounds (0.61 and 1.22 mM) and lapatinib can reduce pHER2, pRas, pSTAT3, and Ki67 expressions compared to control cells. 4TBCB compounds (0.61 and 1.22 mM) can reduce pHER2, pRas, pSTAT3, Ki67 expressions and predicted to inhibit HER2 signaling through the Ras and STAT3 pathways in HER2-expressing breast cancer cells. [ABSTRACT FROM AUTHOR]

Generally, decreased zinc in the serum of tumor patients but increased zinc in tumor cells can be observed. However, the role of zinc homeostasis in myeloid leukemia remains elusive. BCR-ABL is essential for the initiation, maintenance, and progression of chronic myelocytic leukemia (CML). We are currently investigating the association between zinc homeostasis and CML. Genes involved in zinc homeostasis were examined using three GEO datasets. Western blotting and qPCR were used to investigate the effects of zinc depletion on BCR-ABL expression. Furthermore, the effect of TPEN on BCR-ABL promoter activity was determined using the dual-luciferase reporter assay. MRNA stability and protein stability of BCR-ABL were assessed using actinomycin D and cycloheximide. Transcriptome data mining revealed that zinc homeostasis-related genes were associated with CML progression and drug resistance. Several zinc homeostasis genes were affected by TPEN. Additionally, we found that zinc depletion by TPEN decreased BCR-ABL mRNA stability and transcriptional activity in K562 CML cells. Zinc supplementation and sodium nitroprusside treatment reversed BCR-ABL downregulation by TPEN, suggesting zinc- and nitric oxide-dependent mechanisms. Our in vitro findings may help to understand the role of zinc homeostasis in BCR-ABL regulation and thus highlight the importance of zinc homeostasis in CML. [ABSTRACT FROM AUTHOR]

PTEN/AKT signaling cascade is frequently activated in various cancers, including lung cancer. The downstream effector of this signaling cascade is poorly understood. β-Thymosin 10 (TMSB10) functions as an oncogene or tumor suppressors in cancers, whereas its significance in lung cancer remains unknown. In this study, we showed that the activation of PTEN/AKT signaling promoted the expression of TMSB10. Based on the TCGA database, TMSB10 was upregulated in lung cancer tissues and its overexpression was correlated with poor prognosis of lung cancer patients. Functional experiments demonstrated that TMSB10 knockdown suppressed, while its overexpression promoted the proliferation, growth, and migration of lung cancer cells. Apoptosis and epithelial-mesenchymal transition were also regulated by TMSB10. We therefore suggest that TMSB10 is a novel oncogene for lung cancer. Targeting TMSB10 may benefit lung cancer patients with activated PTEN/AKT signaling. [ABSTRACT FROM AUTHOR]

With the development of precise medicine, targeted therapy has greatly improved the survival and prognosis of patients in advanced non-small cell lung cancer (NSCLC) with oncogenic drivers. However, no matter which kinds of targeted therapy are inevitable to develop therapeutic resistance, treatment options upon exhaustion of targeted therapies are limited. Immune checkpoint inhibitors (ICIs) can bring long-term survival to some patients with advanced NSCLC because of its unique long tailing effect. More and more studies have shown that ICIs can also benefit NSCLC patients with oncogenic drivers. However, the timing of ICIs intervention, the therapeutic regimen and the predictive biomarkers are actually debated, underscoring the need to explore the potential interest of ICIs in these populations. [ABSTRACT FROM AUTHOR]

Hairy cell leukemia (HCL) is an uncommon B-cell neoplasm uniquely characterized by a high prevalence of the BRAFV600E mutation, which leads to constitutive activation of the mitogen-activated protein kinase (MAPK) pathway.¹ In fact, the BRAFV600E point mutation is identified in nearly all cases of HCL; however, it is absent in HCL variant (vHCL) and rare in other B-cell neoplasms.2,3 Notably, in contrast to melanoma or other BRAF mutant solid tumors, HCL exhibits very few other mutations, potentially explaining the high response rates observed in patients treated with mutant BRAF-targeted agents, such as vemurafenib. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the roles of COP9 signalosome subunit 8 (COPS8) and its underlying mechanism in cutaneous melanoma. Bioinformatics tools were utilized to analyze the expression of COPS8 in cutaneous melanoma, while Kaplan–Meier analysis was employed to assess the correlation between COPS8 and patients' overall survival. The proliferation, migration, and invasion of cells were estimated by CCK8, colony formation, and Transwell assays. Western blot was used to check the expression of epithelial–mesenchymal transition (EMT)-related proteins. Results showed that COPS8 was up-regulated and predicted a poor clinical outcome for cutaneous melanoma patients. Knockdown of COPS8 inhibited cutaneous melanoma cell proliferation, migration and invasion, whereas overexpression of COPS8 resulted in the opposite outcomes. The up-regulation of E-cadherin and down-regulation of N-cadherin, vimentin, and snail were caused by silencing COPS8 while their expression showed contrary trends in cells with overexpressed COPS8. Collectively, COPS8 is up-regulated and promotes cutaneous melanoma progression via regulating EMT. [ABSTRACT FROM AUTHOR]

Over the past several decades, advances in driven targeted therapy has revolutionized the management of oncogene-driven non-small cell lung cancer (NSCLC). However, there are only a few targeted drugs available for patients with rare mutations, such as BRF, HER2, MET, RET, etc. In recent years, immune checkpoint inhibitors (ICIs) have demonstrated promising benefit in NSCLC. Till now, efficacy of ICIs for NSCLC with rare mutation is largely unknown. It is fairly difficult to conduct a large formal prospective controlled trials because of the rarity of these mutation. In this article, currently available real world studies based on convincing clinical evidence will be reviewed, which will ultimately facilitate our rational use of ICIs for NSCLC with rare mutation. [ABSTRACT FROM AUTHOR]

Extrachromosomal DNA (ecDNA) is a small segment of circular DNA located outside the chromosome, which has the function of self-replication. Recently, amplification of oncogenes on ecDNA has been proved to be a common phenomenon in tumor cells, and has some characteristics worth studying, such as correlation with patients' poor prognosis. Multiple chromosomal events are involved in the formation of ecDNA, and its amplification can directly increase the number of DNA copies of extra-chromosomal oncogenes and accelerate the generation and development of tumors. Moreover, the segregation pattern of unequal transmission of parental ecDNA cells to offspring not only increases tumor heterogeneity, but also enhances tumor adaptation to environment and response to therapy. This article reviews the current status and potential significance of ecDNAin tumor cells. [ABSTRACT FROM AUTHOR]

Lung micropapillary adenocarcinoma is characterized by frequent metastasis, lymph node infiltration, high recurrence rate and low overall survival rate as a high-grade lung adenocarcinoma. Special oncogenic pathway is activated and immune microenvironment is established in this subtype of tumor. This article reviews the Pathological phenomena and molecular features of micropapillary adenocarcinoma studied in recent years, aiming to deepen the understanding of micropapillary lesions and lay the foundation for formulating specific treatment strategies. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is a heterogeneous disease, commonly defined by genetic alterations in oncogenic drivers. Targeted therapies have transformed the management of oncogene-driven lung cancers, with targeted agents now approved in the United States for 7 distinct molecular alterations. Nonetheless, acquired resistance remains an ongoing challenge, underscoring the need for alternative therapeutic approaches. Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1) axis have emerged as important therapies in the management of advanced NSCLC, but the role of these agents in patients with oncogenic driver mutations remains unclear. Here, we focus on epidermal growth factor receptor-mutant and anaplastic lymphoma kinase-rearranged NSCLC as paradigms to explore the role of immune checkpoint inhibitors in oncogene-driven NSCLC. We provide an overview of the clinical data examining programmed death ligand 1 (PD-L1) inhibitor monotherapy, PD-(L)1 inhibitors, and tyrosine kinase inhibitor combinations, as well as combinations of PD-(L)1 inhibitors and chemotherapy. [ABSTRACT FROM AUTHOR]

Mounting evidence has indicated that aberrantly expressed microRNAs (miRNAs) play key roles in tumorigenesis, including in head and neck squamous cell carcinoma (HNSCC). Previous studies have shown that miR‐335‐5p can serve as a tumor suppressor or an oncogene in cancer. However, the clinical importance and biological effects of miR‐335‐5p in HNSCC have not been determined. Here, we investigated the expression pattern, functional role, and mechanisms of miR‐335‐5p in HNSCC. We showed a decreased expression of miR‐335‐5p in HNSCC samples from the TCGA and GEO databases. Consistently, we detected a downregulation of miR‐335‐5p in HNSCC cell lines and patient tissues. The expression of miR‐335‐5p was inversely correlated with advanced clinical TNM stage and lymph node metastasis in HNSCC patients. miR‐335‐5p overexpression inhibited HNSCC cell proliferation and induced apoptosis, while miR‐335‐5p inhibition had the opposite effects. miR‐335‐5p overexpression suppressed tumor growth in mice. Bioinformatic analyses and functional assays identified MAP3K2 as a target of miR‐335‐5p, and we showed that miR‐335‐5p downregulated mitogen‐activated protein kinase kinase kinase 2 (MAP3K2) expression in HNSCC cells. We found an inverse association between MAP3K2 and miR‐335‐5p expression in 38 pairs of HNSCC tissues. Furthermore, the effect of miR‐335‐5p overexpression on growth and metastasis as well as cell apoptosis in HNSCC cells could be partially rescued by MAP3K2 expression. Collectively, our data show that miR‐335‐5p inhibits the development of HNSCC by regulating MAP3K2 expression. Thus, these findings offer novel insights into a potential therapeutic strategy for HNSCC patients. [ABSTRACT FROM AUTHOR]

Lemur tyrosine kinase 3 (LMTK3) is a key member of the serine–threonine tyrosine kinase family. It plays an important role in breast cancer tumorigenesis and progression. However, its biological role in bladder cancer remains elusive. In this study, we demonstrated that LMTK3 was overexpressed in bladder cancer and was positively correlated with bladder cancer malignancy. High LMTK3 expression predicted poor overall survival. Knockdown of LMTK3 in bladder cancer cells triggered cell‐cycle arrest at G2/M phase, suppressed cell growth, and induced cell apoptosis in bladder cancer cells. Furthermore, Transwell assays revealed that reduction of LMTK3 decreased cell migration by regulating the epithelial‐to‐mesenchymal transition pathway. Conversely, LKTM3 overexpression was shown to promote proliferation and migration of bladder cancer cells. We assessed phosphorylation of MEK and ERK1/2 in bladder cancer cells depleted of LMTK3 and demonstrated a reduced phosphorylation status compared with the control group. Using an MAPK signaling‐specific inhibitor, U0126, we could rescue the promotion of proliferation and viability in LMTK3‐overexpressing cells. In conclusion, we extend the status of LMTK3 as an oncogene in bladder cancer and provide evidence for its function via the activation of the ERK/MAPK pathway. Thus, targeting LMTK3 may hold potential as a diagnostic and prognostic biomarker and as a possible future treatment for bladder cancer. [ABSTRACT FROM AUTHOR]

The discovery of the von Hippel-Lindau (VHL) gene marked a milestone in our understanding of clear cell renal cell carcinoma (ccRCC) pathogenesis. VHL inactivation is not only a defining feature of ccRCC, but also the initiating event. Herein, we discuss canonical and noncanonical pVHL functions, as well as breakthroughs shaping our understanding of ccRCC evolution and evolutionary subtypes. We conclude by presenting evolving strategies to therapeutically exploit effector mechanisms downstream of pVHL. [ABSTRACT FROM AUTHOR]

Background and objective Leptomeningeal metastasis (LM) are a severe complication of non-small cell lung cancer (NSCLC), and normally accompanied by poor prognosis. For the patients with targetable mutations, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the preferred treatment, but the acquired TKI resistance is inextricable. The aim of this study is to analyze the different gene mutation spectrum and mutation frequency of the cerebrospinal fluid (CSF) and plasma in NSCLC patients with LM, and screen out the drug-resistant mutations so as to guide the choice of treatment accurately. Methods The paired CSF and plasma samples were collected from the NSCLC-LM patients with acquired TKI resistance. Next generation sequencing (NGS) was used to detect the gene variations of circulating tumor DNA (ctDNA). Results A total of 18 NSCLC patients with LM were collected. Of the basic mutations, 11 cases (61.11%) were EGFR, 6 cases (33.33%) were anaplastic lymphoma kinase (ALK), and 1 case (5.56%) was ROS proto-oncogene 1, receptor tyrosine kinase (ROS1). Tumor protein p53 gene (TP53) and mesenchymal-epithelial transition factor (MET) were the two most frequently accompanying mutated genes in CSF ctDNA. The detected mutation rate of CSF samples was higher than that of plasma samples (100.00% vs 66.67%, P=0.006), and the maximum allelic fractions were all higher in CSF than in plasma (P<0.001). Abundant single-nucleotide variations (SNV) and copy number variants (CNV) were detected in CSF, the amount of both of which were more than in blood. In addition, the CSF and plasma samples of patients treated with several TKIs had more SNV mutations than patients who received only a single TKI treatment. Conclusion For the patients of NSCLC, ctDNA in CSF could reveal genomic alterations of LM more exactly and overally than it in plasma, thus could be an optimal source of liquid biopsy for guiding therapy, monitoring therapeutic effect, and predicting prognosis. [ABSTRACT FROM AUTHOR]

The aim of the present study was to assess the effects of different silicate-based sealers (ie, BioRoot RCS [Septodont, Saint Maur des Fosses, France], ProRoot ES [Dentsply Sirona, York, PA], and MTA Fillapex [Angelus, Londrina, PR, Brazil]) on cytokine production and viability of human periodontal ligament stem cells (PDLSCs). AH Plus (Dentsply DeTrey GmbH, Konstanz, Germany) was used as a reference material. PDLSCs were cultured either in 2-dimensional or 3-dimensional conditions (in 0.15%–0.5% PuraMatrix [BD Biosciences, Bedford, MA]) for 24 hours with eluates from set endodontic sealers. Additionally, the toxicity of eluates from endodontic sealers was evaluated using an in vitro root model experimental procedure. PDLSC viability was determined using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. PDLSC culture medium was used for cytokine quantification (interleukin [IL]-6, IL-8, growth-regulated oncogene, IL,-4 and IL-10) using the HCYTMAG-60K-PX41 Milliplex kit (EMD Millipore, Burlington, MA). In 2-dimensional culture conditions, BioRoot RCS revealed a good PDLSC viability rate. ProRoot ES had no effect on PDLSC viability regardless of the dilution. MTA Fillapex was strongly cytotoxic even at the lowest extract dilutions (1:1, 1:2, and 1:4). Encapsulation of PDLSCs in PuraMatrix tended to decrease the cytotoxic effect of the sealers. In the 3-dimensional in vitro root model experimental procedure, BioRoot RCS, ProRoot ES, and MTA Fillapex revealed a cytocompatibility pattern. Different calcium silicate–based sealers exhibited different proinflammatory cytokine production. BioRoot RCS greatly stimulated the release of IL-10 and, to a lesser degree, IL-4 by PDLSCs (P <.05). BioRoot RCS and ProRoot ES did not induce proinflammatory cytokines and promoted anti-inflammatory cytokine secretion by PDLSCs that may have a positive local impact by attenuating an initial inflammatory response. [ABSTRACT FROM AUTHOR]

Young adult lung cancer is defined as a group of patients refers to whose onset age is less than 40 years old and ≥18 years old. Compare with elder lung cancer, the clinical symptoms of them are not typical, the stage is usually late at the time of discovery, and most of them have regional lymphatic metastasis or distant metastasis. Current study found that young adult lung cancer has a relatively unique genetic background, the abundance of tumor-driving genes is high, and it is closely related to its clinical manifestation and prognosis. Young adult lung cancer is the focus of attention in the field of cancer in recent years. This article reviewed the literature on the clinical features, gene phenotypic characteristics and prognosis of young adult lung cancer in order to provide provide some references and clues for the study on young adult lung cancer. [ABSTRACT FROM AUTHOR]