Malignant Features Research Articles

Clinical significance and pro-oncogenic function of DBF4 in clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is the most common malignant urological tumor, and regrettably, and is insensitive to chemotherapy and radiotherapy, resulting in poor patient outcomes. DBF4 plays a critical role in DNA replication and participates in various biological functions, making it an attractive target for cancer treatment. However, its significance in ccRCC has not yet been explored.MethodsWe utilized external datasets and bioinformatics analyses to investigate the significance of DBF4 in ccRCC. We analysed its expression patterns, prognostic and diagnostic value, and potential mechanisms. We subsequently validated our findings through an immunohistochemistry (IHC) assay of ccRCC clinical samples. We further investigated the impact of DBF4 on the progression of ccRCC cells. Various assays, including assessments of cell proliferation, apoptosis, the cell cycle, cell migration and invasion, and colony formation, and xenograft tumor models were subsequently performed following to the knockdown of DBF4 expression via shRNA.ResultsBioinformatics analyses revealed that DBF4 is significantly overexpressed in ccRCC tissues compared with adjacent normal tissues. This overexpression was confirmed by IHC analysis of 75 pairs of clinical ccRCC tumor and adjacent tissues. Kaplan-Meier analysis revealed that high DBF4 expression was associated with a significantly lower five-year overall survival rate. Moreover, DBF4 expression was identified as an independent risk factor in multivariate Cox regression analysis. GO and KEGG pathway enrichment analyses revealed a substantial enrichment of terms associated with cell division, whereas gene set enrichment analysis (GSEA) revealed correlations between increased DBF4 expression and the activation of cell cycle-related pathways. Subsequent in vitro and in vivo experiments demonstrated that DBF4 knockdown in ccRCC cells not only suppressed proliferation and migration in vitro but also significantly inhibited tumor growth in xenograft mice by arresting the cell cycle at the G1/G0 phase, which was mediated by the inhibition of MCM2 phosphorylation and cyclin D1 and CDK4 expression.ConclusionThe current study revealed that DBF4 overexpression is a significant factor associated with malignant features and poor prognosis in patients with ccRCC. Therefore, it was proposed that DBF4 could serve as a novel potential prognostic biomarker and molecular target for ccRCC.Clinical trial numberNot applicable.

Malignant breast adenomyoepithelioma: case report and literature review

Malignant adenomyoepithelioma (MAME) of the breast is a rare tumor with both benign and malignant features. We report a case of a 67-year-old woman who presented with a mass in the outer quadrant of the right breast, detected during a routine check-up. The mass was classified as BI-RADS 3. After minimally invasive excision, pathology confirmed low-grade malignant adenomyoepithelioma. The patient then underwent total mastectomy and sentinel lymph node biopsy (SLNB). At two years of follow-up, there was no recurrence or metastasis. This case highlights the rarity of MAME and the importance of early diagnosis and complete excision.

RNA m6A involves in regulation of oxidative stress and apoptosis may via NF-kB pathway in cadmium-induced lung cells

Cadmium has been identified as an environmental pollutant and a carcinogen. N6-methyladenosine (m6A) plays a crucial role in the development of lung tumors, but the mechanisms remain incompletely clarified. In present study, our data demonstrated that prolonged treatment of 1 μmol/L CdSO4 for 40 passages in bronchial epithelial cells (Beas-2B cells) resulted in the development of a malignant phenotype, which manifested as boosted proliferation, migration and invasion capacity as well as apoptosis reduction. Proteomic assay revealed that in passage 40 cells, 350 proteins showed differentially expressed in comparison to control, and these proteins were primarily enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of “pathways in cancer” and “Chemical carcinoma-reactive oxygen species”. Moreover, the mRNAs of Nuclear factor kappa B (NF-κB) p65 and NAD(P)H: quinone oxidoreductase 1 (NQO1), the key signaling molecules in these two signaling pathways, were predicted to contain m6A modification sites with high confidence. The subsequent experimental results indicated that levels of m6A and Fat mass and obesity associated protein (FTO) elevated, while Alkylated DNA repair protein alkB homolog 5 (ALKBH5) and YTH Domain Containing Protein 2 (YTHDC2) reduced with the increasing of cadmium treatment generations. Furthermore, the reduction of m6A levels by 3-deazide adenosine (DAA, m6A inhibitor) was found to significantly inhibit malignant characteristics of cadmium-induced cells, activate molecules involved in the nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway, and inhibit the activity of NF-κB. It is also noteworthy that the results based on animals indicate that the relevant indicators and biological changes are partially similar to cell experiments. In detail, m6A modification levels in lung tissue were observed to increase while the expressions of FTO, ALKBH5 and YTHDC2 were found to drop. Additionally, immunofluorescence examination illustrated the co-localization of the m6A regulatory proteins FTO and YTHDC2 with NF-κB. The presented data collectively suggest that chronic cadmium treatment may impact the m6A level through influencing regulatory proteins, which could potentially trigger oxidative stress and apoptosis by regulating transcription factors such as NF-κB and NRF2. In conclusion, our study provides a scientific foundation for understanding cadmium toxicity and offers novel insights for treating cadmium-induced lung diseases.

High matrix stiffness accelerates migration of hepatocellular carcinoma cells through the integrin β1-Plectin-F-actin axis

BackgroundAbundant research indicates that increased extracellular matrix (ECM) stiffness significantly enhances the malignant characteristics of hepatocellular carcinoma (HCC) cells. Plectin, an essential cytoskeletal linker protein, has recently emerged as a promoter of cancer progression, particularly in the context of cancer cell invasion and metastasis. However, the responsiveness of plectin to changes in ECM stiffness and its impact on HCC progression remain unclear. In this study, we aimed to investigate whether plectin responds to variations in ECM stiffness and to explore its involved molecular mechanisms in regulating HCC cell migration.ResultsOur results showed that, when compared with control group (7 kPa), high ECM stiffness (53 kPa) boosts HCC cell migration by upregulating plectin and integrin β1 expression and increasing F-actin polymerization. Knockdown of integrin β1 negated the high stiffness-upregulated plectin expression. Furthermore, reducing either plectin or integrin β1 levels, or using latrunculin A, effectively prevented the high ECM stiffness-induced F-actin polymerization and HCC cell migration.ConclusionsThese findings demonstrate that integrin β1-plectin-F-actin axis is necessary for high matrix stiffness-driven migration of HCC cells, and provide evidence for the critical role of plectin in mechanotransduction in HCC cells.

Benign or Malignant? Ex Vivo Confocal Laser Scanning Microscopy for Bedside Histological Assessment of Melanocytic Lesions.

Ex vivo confocal laser scanning microscopy (EVCM) is an emerging imaging technique, which offers rapid tissue examination. While the current literature shows promising results in the evaluation of non-melanoma skin cancer, only limited research exists on the application of EVCM in melanocytic lesions. This study aimed to assess the utility of EVCM in the characterization of melanocytic lesions and compare its findings with gold-standard histopathology. A total of 130 skin lesions, including 76 benign and 54 malignant melanocytic lesions, were prospectively collected and imaged using EVCM. Three blinded investigators were asked to identify characteristic morphologic features observed in the lesions and classify them into benign vs. malignant. The results were then compared with the corresponding histopathology. Sensitivity and specificity were calculated using contingency tables to assess the diagnostic performance. The application of EVCM allowed for the visualization of cellular and tissue-level details, including cellular pleomorphism and atypical melanocytes. A comprehensive list of benign and malignant features identified by EVCM was compiled. Using these diagnostic criteria, the imaging of the inexperienced and dermatohistopathology-experienced investigator reached 67.7% concordance, and the imaging trained dermatologist obtained 69.2% agreement with dermatohistopathology in differentiating benign vs. malignant lesions. The imaging-trained dermatohistopathologist performed best with concordance up to 79.2%. In conclusion, EVCM is a promising technique for the rapid assessment of melanocytic lesions. Our study provides a comprehensive overview of morphologic EVCM features, which will contribute to the development of diagnostic algorithms for accurate diagnosis and appropriate treatment planning. Further studies are needed to evaluate its clinical utility and validate our diagnostic criteria.

Depletion of TP53 in Human Pluripotent Stem Cells Triggers Malignant-Like Behavior.

Human pluripotent stem cells (hPSCs) tend to acquire genetic aberrations upon culture in vitro. Common aberrations are mutations in the tumor suppressor TP53, suspected to confer a growth-advantage to the mutant cells. However, their full impact in the development of malignant features and safety of hPSCs for downstream applications is yet to be elucidated. Here, TP53 is knocked out in hPSCs using CRISPR-Cas9 and compared them with isogenic wild-type hPSCs and human germ cell tumor lines as models of malignancy. While no major changes in proliferation, pluripotency, and transcriptomic profiles are found, mutant lines display aberrations in some of the main chromosomal hotspots for genetic abnormalities in hPSCs. Additionally, enhanced clonogenic and anchorage-free growth, alongside resistance to chemotherapeutic compounds is observed. The results indicate that common TP53-depleting mutations in hPSCs, although potentially overlooked by standard analyses, can impact their behavior and safety in a clinical setting.

Ginsenoside RK3 inhibits glioblastoma by modulating macrophage M2 polarization via the PPARG/CCL2 axis

BackgroundGlioblastoma is recognized as the most aggressive form of intracranial tumor, presenting significant challenges in treatment. Recent emphasis has been placed on the potential of traditional Chinese medicine (TCM) as an adjuvant treatment for cancer. Methods: We employed a series of assays—including CCK8, EdU, Transwell, and neurosphere formation—to evaluate the impact of ginsenoside RK3 on the phenotype of GBM. The modulation of macrophage M2 polarization by ginsenoside RK3 was assessed through flow cytometry, immunohistochemistry, and Western blot analysis. Furthermore, we utilized sequencing analysis and network pharmacology to identify potential therapeutic targets. ResultsOur findings reveal that ginsenoside RK3 not only inhibits the phenotype of glioblastoma cells but also suppresses tumor progression in vivo while attenuating macrophage M2 polarization within the tumor immune microenvironment. Notably, ginsenoside RK3 down-regulates PPARG expression in tumor cells, leading to decreased secretion of CCL2, which subsequently diminishes macrophage M2 polarization. Additionally, we demonstrated that combining ginsenoside RK3 with temozolomide significantly enhances the inhibition of glioblastoma's malignant characteristics and progression. ConclusionsThis study innovatively highlights the dual mechanism of ginsenoside RK3 in glioblastoma treatment: it impedes tumor progression by modulating the PPARG/CCL2 pathway and enhances the efficacy of temozolomide. Our research underscores the promising role of herbal medicine in the management of glioblastoma, paving the way for novel therapeutic strategies that integrate traditional approaches with conventional treatments.

AMPK: an energy sensor for Non-small cell lung cancer progression and treatment.

Lung cancer (LC) is the leading cause of cancer-related morbidity and mortality in China, with non-small cell lung cancer (NSCLC) accounting for 85% of the overall lung cancer cases. AMP-activated protein kinase (AMPK) is a key regulator of energy balance and homeostasis, and its dysregulation is a common feature in various malignancies, particularly in NSCLC with mutations in Liver kinase B1 (LKB1). Studies have shown that the AMPK signalling pathway has a dual role in NSCLC progression, both inhibiting and promoting the progression of malignant tumours. Therefore, drugs targeting the AMPK signalling pathway may hold significant promise for therapeutic application in NSCLC. This review aims to examine the manifestations and mechanisms by which AMPK and its associated signalling molecules influence NSCLC progression and treatment. Firstly, we discuss the critical importance of AMPK within the mutational context of NSCLC. Secondly, We summarise the drugs and related substances that modulate the AMPK signalling pathway in NSCLC and evaluate the evidence from preclinical studies on combination AMPK-targeted therapies to address the issue of drug resistance in NSCLC under current clinical treatments. In summary, this paper highlights the critical importance of developing AMPK-targeted drugs to enhance therapeutic efficacy in NSCLC, as well as the potential for applying these drugs in clinical therapy to overcome drug resistance.

Efficacy of ultrasonography and mammography in detecting features of breast cancer

ABSTRACT Introduction: Breast cancer (BC) is considered one of the most commonly diagnosed cancers. Early detection is critical for effective management. This study aims to assess the utility of ultrasonography (US) and mammography (MG) in detecting BC features. Methods: This retrospective cross-sectional study involved the electronic records of 263 female patients diagnosed with BC. The mean age was 45.71 ± 12.25 years (17–90 years). A cross-tabulation test was performed to correlate the presence of each malignant feature (Yes/No) on both US and MG and the final ultrasonography diagnosis (benign/malignant). The compatibility between the presence of each feature on both imaging techniques was measured by the percentage of agreement in reporting the feature that was reported as Kappa. The sensitivity and specificity for each feature were calculated, and the receiver operating characteristic curve was used to measure the area under the curve for each feature on both modalities. Results: The strong compatibility between the two techniques was 87.1%, 94.29%, 66.92%, 79.85%, 77.56%, 77.18, and 79.84% for irregular shape, uncircumscribed, spiculated margins, tissue distortion, nipple retraction, skin thickening, and the presence of lymphadenopathy, respectively (P < 0.001). Boxplots show that the sensitivity of the US ranged from 37% to 95%, and the specificity ranged from 27% to 91%. However, MG’s sensitivity ranged from 44% to 93%, and the specificity ranged from 36% to 73%. Conclusion: US and MG images show similar morphological changes, enhancing diagnostic accuracy in breast lesions. US characterizes echogenicity, provides real-time imaging, and uses color and pulsed Doppler techniques for vascularity and lymphadenopathy detection, while MG is better for identifying different calcification types.

Network pharmacological mechanism and molecular experimental validation of artemisinin in the treatment of lung adenocarcinoma.

Lung cancer is a medical ailment with high mortality and prevalence rates. Artemisinin (ART) and its derivatives exhibit anti-cancer properties against various malignancies, including lung cancer. However, further research is required to determine the precise anti-cancer mechanisms of ART. Hence, this study aimed to utilize network pharmacology to preliminarily investigate the therapeutic effectiveness and mode of action of this medication. Using a bioinformatics approach, five target proteins with the strongest connections were selected for docking. Gene enrichment analysis was performed, and the ART target proteins were predicted. Various methods, including methyl thiazolyl tetrazolium (MTT) assays, colony formation assays, microsphere formation assays, flow cytometry, and western blotting analysis, were employed to assess the impact of ART on the malignant characteristics of lung cancer cells. Bioinformatic analysis identified 51 ART target genes in lung adenocarcinoma for further analysis. Pathway enrichment analysis of target genes revealed 639 enriched Gene Ontology-Biological Process (GO BP) and 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. These findings imply that ART may control the IL-6 signaling pathway by focusing on important molecules such as CDK4 and IL-6. The ART-treated group experienced apoptosis induction, cell cycle arrest, and inhibition of cell proliferation and microsphere formation compared with the control group (p<0.05, p<0.01). Additionally, ART reduced the protein expression of CDK4, COX2, ERBB2, CD44, and EpCAM while increasing that of caspase 3, IL-6, p53, and SRC (p<0.01). ART inhibited the growth and stemness of HCC827 cells.

Aloe arborescens Standardized Glycosidic Fraction Suppresses Hepatocarcinoma by Modulating TIMP1, MMP9 Genes Expression, and Inflammation/Ki67/TGFβ1 Pathway.

(1) Background and aim: Aloe arborescens Mill. (A. arborescens) is one of the most widely distributed species in the genus Aloe and has garnered widespread recognition for its anticancer properties. However, the molecular mechanisms underlying these activities have not yet been fully elucidated. This study aimed to explore the effects of the plant polar glycosidic fraction (AAG) on hepatocellular carcinoma (HCC) in an invivo model induced by diethylnitrosamine (DEN). (2) Experimental procedure: The fraction was standardized using HPLC-PDA-MS/MS fingerprinting, and two distinct intragastric AAG dose regimens were examined (10 and 20 mg/kg) in combination with DEN 200 mg/kg. Serum alpha-fetoprotein (AFP), gamma-glutamyl transferase (γ-GGT), glutathione S-transferase placental (GST-P), mRNA expression of metabolic cytochrome enzymes (CYP1A3 and CYP2B2), inflammatory genes (nuclear factor kappa-B p65 subunit; NF-κB p65), metalloproteases 9 (MMP9), tissue inhibitors of metalloproteases (TIMP1), transforming growth factor beta 1 (TGFβ1), and histological features were assessed. (3) Key results and conclusions and implications: AAG was characterized by five major secondary metabolites: saponins, chromones, anthraquinone, and triterpenes. The fraction reduced hepatic malignancy characteristics by diminishing the size and number of altered foci and lowering hepatic cancer biomarkers, such as γ-GGT, AFP, and GST-positive foci. It also reduced the mRNA levels of CYP1A3 and CYP2B2, NF-κB p65, and MMP9, hepatic Ki-67, and TGFβ1 while upregulating TIMP1 levels. This study revealed that AAG exhibited a marked suppressive effect on HCC cell proliferation, displaying a range of mechanistic actions, including decreasing the metabolic activation of cytochrome enzymes, which consequently reduced the production of reactive oxygen species and other genes implicated in cancer development. AAG could be a significant therapeutic candidate for patients diagnosed with hepatocarcinoma.

Performance of Ulcer Features in Predicting Malignancy Among Gastric Ulcers Diagnosed on Upper Endoscopy

Objective: Even though the prevalence of malignancy within gastric ulcers is low, surveillance endoscopy is routinely performed after gastric ulcer diagnosis resulting in unnecessary costs and risks. Endoscopic appearance may be used to identify ulcers with malignant features and guide decisions regarding the need for surveillance endoscopy. Our aim was to assess the predictive value of several endoscopic ulcer features with the risk of prevalent malignancy in patients diagnosed with gastric ulcers. Methods: Patients with gastric ulcers were identified using endoscopic reporting software in 2 hospitals in Houston, TX, from February 2019 to July 2021. Malignant and benign gastric ulcers were defined using ulcer biopsy histopathology, and ulcers that had healed on surveillance endoscopy were also classified as benign ulcers. Potential endoscopy-related predictors of malignant ulcers included: Forrest classification, location, size, elevated border, irregular border, and background gastric atrophy. Results: We identified 338 patients with gastric ulcers, and 150 (44%) had at least one surveillance endoscopy. Malignant ulcers were found in 41 patients (12%). The strongest predictors of malignancy were irregular border [area under receiver operating characteristic (AUROC): 0.89, 95% CI: 0.80-0.97], gastric atrophy on histopathology (AUROC: 0.87, 95% CI: 0.78-0.96), and elevated border (AUROC: 0.84, 95% CI: 0.73-0.95). A multivariate model including corpus/cardia location, irregular border, elevated border, and gastric atrophy on histopathology had the best discrimination for predicting malignant ulcers (AUROC: 0.96, 95% CI: 0.93-0.98) with low false negatives (0.4%). Conclusions: A model combining corpus/cardia location, irregular border, elevated border, and gastric atrophy on histopathology best-predicted malignancy in gastric ulcers and may identify patients with the most benefit from surveillance endoscopy.

GPR37-enhanced ubiquitination of ATP1A1 inhibits tumor progression and radiation resistance in esophageal squamous cell carcinoma

Radiotherapy resistance is one of the main reasons for the dismal clinical outcome of patients with esophageal squamous cell carcinoma (ESCC). Therefore, clarifying the targets and molecular mechanisms of radiotherapy resistance in ESCC is of great theoretical and clinical significance to enhance the efficacy of radiotherapy. In this study, GPR37 was identified as a key factor facilitating ESCC radiosensitization. We found that GPR37 is lowly expressed in ESCC, especially in radioresistant ESCC tumors. And its insufficiency is related to the malignant characteristics and unfavorable prognosis in ESCC. Further investigation revealed that GPR37 level is inversely regulated by promoter methylation but positively regulated by ZNF750. Functionally, GPR37 could not only overcome radioresistance of ESCC, but also inhibit proliferation, migration, and invasion. Mechanistically, GPR37 interacts with the ATP1A1 protein, effectively promoting its ubiquitination-induced degradation, thereby limiting the activation of the AKT/mTOR signaling pathway. Additionally, GPR37 can be transported to recipient cells via exosomes and inhibit the malignant behavior of recipient cells. Overall, these findings suggest that GPR37-ATP1A1 axis holds potential as a therapeutic target for the management of ESCC, especially for overcoming radiation resistance.

PGRN protects against serum deprivation-induced cell death by promoting the ROS scavenger system in cervical cancer

Progranulin (PGRN), an autocrine growth factor with tumorigenic roles in a variety of tumors, is a putative survival factor for normal and cancer cells in vitro. However, the fundamental mechanism of PGRN-mediated survival of cancer cells suffering from various types of microenvironmental stresses, such as serum deprivation, remains unknown. We show here that serum deprivation decreases intracellular PGRN protein levels in cervical cancer cells. PGRN protects cervical cancer cells against serum deprivation-induced apoptosis, limits reactive oxygen species (ROS) levels, maintains mitochondria integrity, and reduces oxidative damage of protein, lipid and DNA. PGRN enhances the ROS scavenger system, as evidenced by increased superoxide dismutase (SOD), catalase protein expression and activity, elevated GSH and NADPH levels and increased phase II detoxification enzyme expression in cervical cancer cells after serum withdrawal. The role of PGRN in ROS clearance is mediated by the PGRN-stimulated nuclear factor erythroid-derived 2-like 2 (NFE2L2)-antioxidant response element (ARE) pathway. Our study reveals an antioxidant role of PGRN in supporting the survival of cervical cancer cells under oxidative stress. This insight provides a new perspective on the how cervical cancer cells adapt to microenvironmental stress, contributing to cell viability and other malignant characteristics.

Different prevalence and spectrum of malignancy between Chinese patients and American patients with rheumatoid arthritis: a comparative study.

To characterize the epidemiological characteristics of malignancy in Chinese patients with rheumatoid arthritis (RA) versus American patients and investigate their associated factors. Data were collected from a real-world Chinese RA population and American patients with RA from the National Health and Nutritional Examination Survey. The prevalence and subtypes of malignancy and their potential associated factors were investigated in both populations. A total of 2,073 Chinese and 2,928 American patients with RA were included. There was a lower prevalence of malignancy in Chinese than in their American counterparts before (5.7% vs. 17.1%) and after matching (6.2% vs. 12.6%, both P < 0.001). Gender discrepancies in malignancy prevalence were observed, with a male predilection for RA with malignancy in China (8.2% vs. 5.5%), while it was the opposite in American patients (10.1% vs. 13.5%, both P < 0.05). The top type of malignancy among male patients with RA was lung cancer in Chinese (2.29%), but non-melanoma skin cancer (3.43%) in American; while among female patients was breast cancer both in Chinese (1.72%) and American (3.43%). Multivariate logistic regression analyses showed that older age (odds ratio (OR) = 1.050) and positive anti-cyclic citrullinated peptide antibody (OR = 2.752) were independently associated with malignancy in Chinese patients with RA, while female (OR = 1.395), older age (OR = 1.033), active smoking (OR = 1.580) and cardiovascular diseases (OR = 1.523) in American patients. The prevalence, subtypes and risk factors of malignancy were substantially different in Chinese patients with RA and their American counterparts, which implied the importance of individualized malignancy screening strategies for patients with RA.

Interleukin-22 promotes endometrial carcinoma cell proliferation and cycle progression via ERK1/2 and p38 activation.

Endometrial carcinoma (EC) is one of the most common gynecological malignant tumors, but its underlying pathogenic mechanisms are largely obscure. Interleukin-22 (IL-22), one cytokine in the tumor immune microenvironment, was reported to be associated with carcinoma progression. Here, we aimed to investigate the regulation of IL-22 in endometrial carcinoma. Enzyme-linked immunosorbent assay (ELISA) analysis of IL-22 was done in 27 controls and 51 patients with EC. We examined the proliferative potential, cycle progression, and signaling pathways modulated by IL-22 in EC cells. Western blot analysis was performed to investigate the expression of proliferative and cycle-related proteins in EC cells. The effect of IL-22 mediated by interleukin-22 receptor alpha 1 (IL-22RA1) was examined using cell transfection with small interfering RNA (siRNA). In addition, a xenograft tumor model was performed to assess the effect of IL-22 in vivo. We demonstrated significant up-regulation of serum IL-22 concentrations in EC patients (42.59 ± 23.72pg/mL) compared to the control group (27.47 ± 8.29pg/mL). High levels of IL-22 concentrations appear to correlate with malignant clinicopathological features of EC. Treatment with IL-22 promoted cell proliferation and G1/S phase progression in Ishikawa and HEC-1B cells. Western blot analysis revealed that c-Myc, cyclin E1, cyclin-dependent kinase (CDK)2, cyclin D1, CDK4, CDK6, p-extracellular signal-regulated kinase1/2 (p-ERK1/2), and p-p38 were highly expressed in EC cells exposed to IL-22. Moreover, in the EC mice model, we found that giving exogenous IL-22 increased tumor volume and weight. Immunohistochemistry showed that intra-tumor Ki-67 expression was up-regulated upon IL-22 treatment. The IL-22-mediated changes in cell proliferation, cycle progression, and protein expression can be effectively inhibited by the ERK1/2 inhibitor U0126 and the p38 inhibitor SB202190. In addition, the role of IL-22 in EC is receptor-dependent. Our findings suggest that IL-22 promotes endometrial carcinoma cell proliferation and G1/S phase progression by activating ERK1/2 and p38 signaling. Therefore, IL-22 may represent a potential therapeutic target for the treatment of endometrial carcinoma.

Gastric Cytology: A Supplement to Early Diagnosis of Gastric Malignancies.

Gastric malignancies are one of the leading causes of morbidity and mortality globally. Rapid accurate interpretation of gastric cytology aids in early diagnosis and management. This study evaluates the utility of gastric cytology in diagnosing gastric malignancies. This retrospective, cross-sectional study was conducted in the Department of Pathology for a period of 3.5 years. The cases with clinical suspicion of gastric malignancy and those who have had both cytology and histopathology examinations were included. Cytology results were reported as positive for malignancy, suspicious for malignancy, atypical cells-favor reactive, and negative for malignancy. The cytology and histopathology results were correlated, and descriptive statistics were used to analyze data. Among 118 patients included in the study, 103 cases were malignant and 15 were nonmalignant. Out of 103 malignant cases, 89 cases were detected in cytology. False positive cases consisted of four gastritis cases with florid reactive atypia and one with moderate dysplasia. False negative cases were of diffuse and intestinal subtypes of adenocarcinoma, followed by non-Hodgkin lymphoma. Sensitivity and specificity were found to be 86.41% and 66.67%, respectively. The positive predictive value is 94.68% with 41.67% negative predictive value and a diagnostic accuracy of 83.90%. Gastric cytology is a reliable screening and diagnostic tool with a high positive predictive value and acceptable sensitivity. Negative cytology in suspected cases of gastric malignancy should always be correlated with biopsy reports. Diffuse type, intestinal type gastric adenocarcinoma and non-Hodgkin lymphoma were the major pitfall on cytology. The cells in the background must be meticulously observed for the malignant features. Gastric cytology is cost-effective and yields rapid diagnosis with a high positive predictive value, sensitivity, and diagnostic accuracy.

Primary Extra-axial Glioblastoma Mimicking Meningioma: Case Report and Review of Literature

Glioblastoma (GBM) is the most common malignant brain tumour in adults. On radiology, diagnostic dilemmas can arise with other brain pathologies like metastasis, brain abscess, and lymphoma. However, GBM mimicking a meningioma on radiology has been rarely reported. Here, we report a case of GBM with magnetic resonance imaging (MRI) features suggestive of meningioma. A 46-year-old female presented with a one-month history of headaches. The MRI brain suggested a broad-based extra-axial mass lesion in the left frontal convexity with cerebrospinal fluid (CSF) cleft sign with compression of underlying brain parenchyma. Overall, the MRI brain was suggestive of a cystic meningioma. The patient underwent gross total resection of the tumour under microscopy, and final histopathology confirmed GBM. Although GBM is usually an intra-axial tumour, it may present as an extra-axial mass lesion with radiological features mimicking meningioma. Therefore, it should be considered a differential diagnosis in patients with an extra-axial tumour displaying atypical malignant features.

Characterization of exclusive rib lesions detected by [ 68 Ga]Ga-PSMA-11 PET/CT.

The objective of this study was to characterize exclusive costal lesions detected by 68 Gallium-labelled prostate-specific membrane antigen ([ 68 Ga]Ga-PSMA-11) PET/computed tomography (CT) at initial staging or biochemical recurrence (BCR) in prostate cancer (PCa) patients, and to identify clinical and/or PET/CT criteria associated with benign and malignant lesions. We retrospectively identified 54 patients with PCa who underwent [ 68 Ga]Ga-PSMA-11 PET/CT for initial staging ( N = 39) or BCR ( N = 15) and whose reports described rib lesions, at the exclusion of any other lesions, whether doubtful, suspicious, or established. Posttherapy prostate-specific antigen (PSA) levels were used to determine whether those lesions were benign or malignant. Each patient's prostate-specific membrane antigen PET/CT report was classified as true positive, true negative, false positive, or false negative based on the posttherapy PSA level. We then assessed whether any clinical and/or PET/CT criteria could help differentiate benign from malignant lesions, and if any criteria were misleading. Among the 54 patients, 46 (85.2%) had 64 benign costal lesions, and eight (14.8%) had 10 malignant lesions. PET/CT reports indicated rib lesions as benign/equivocal in 38/54 (55.6%) patients and malignant in 16/54 (29.6%). Benign features on CT were the only parameter significantly associated with the final diagnosis. Factors such as patient age, maximum standardized uptake value of lesions, lesion dispersion, and malignant features described on CT were found to be misleading when deciding the malignant or benign status. Most exclusive costal lesions detected by [ 68 Ga]Ga-PSMA-11 PET/CT are benign. Apart from specific benign CT features, no clinical or PET/CT criteria reliably differentiate benign from malignant costal lesions.

LncRNA C7orf13 facilitates cell proliferation and metastasis in nasopharyngeal carcinoma via targeting miR‐449c/miR‐28‐5p‐FMNL2 axis

AbstractThis study was to determine the involvement of long non‐coding RNA C7orf13 in nasopharyngeal carcinoma (NPC) and its underlying mechanism. Real‐time quantitative PCR results indicated that C7orf13 was overexpressed in NPC and associated with malignant features. C7orf13 knockdown significantly suppressed the proliferation, migration and invasion of NPC cells. Furthermore, we found that C7orf13 sequestered miR‐449c and miR‐28‐5p in NPC cells by dual‐luciferase reporter assays and RNA immunoprecipitation analysis. Sequent experiments showed that C7orf13 has a positive relationship with formin‐like 2 (FMNL2) in NPC tissues. Moreover, C7orf13 knockdown weakened FMNL2‐mediated cell invasion and migration. Finally, functional experiments revealed that the positive effect of C7orf13 on cell migration and invasion was mediated by the miR‐449c/miR‐28‐5p‐FMNL2 axis. Generally, our study identifies the biological role of long non‐coding RNA C7orf13 in the malignant process of NPC, which may pave a new way for the diagnosis and treatment of NPC.