Common Tumor Research Articles

Multi-omics and pharmacological characterization of patient-derived glioma cell lines

Glioblastoma (GBM) is the most common brain tumor and remains incurable. Primary GBM cultures are widely used tools for drug screening, but there is a lack of genomic and pharmacological characterization for these primary GBM cultures. Here, we collect 50 patient-derived glioma cell (PDGC) lines and characterize them by whole genome sequencing, RNA sequencing, and drug response screening. We identify three molecular subtypes among PDGCs: mesenchymal (MES), proneural (PN), and oxidative phosphorylation (OXPHOS). Drug response profiling reveals that PN subtype PDGCs are sensitive to tyrosine kinase inhibitors, whereas OXPHOS subtype PDGCs are sensitive to histone deacetylase inhibitors, oxidative phosphorylation inhibitors, and HMG-CoA reductase inhibitors. PN and OXPHOS subtype PDGCs stably form tumors in vivo upon intracranial transplantation into immunodeficient mice, whereas most MES subtype PDGCs fail to form tumors in vivo. In addition, PDGCs cultured by serum-free medium, especially long-passage PDGCs, carry MYC/MYCN amplification, which is rare in GBM patients. Our study provides a valuable resource for understanding primary glioma cell cultures and clinical translation and highlights the problems of serum-free PDGC culture systems that cannot be ignored.

Intracranial meningioma: A review of recent and emerging data on the utility of preoperative imaging for management.

Meningiomas are the most common neoplasms of the central nervous system, accounting for approximately 40% of all brain tumors. Surgical resection represents the mainstay of management for symptomatic lesions. Preoperative planning is largely informed by neuroimaging, which allows for evaluation of anatomy, degree of parenchymal invasion, and extent of peritumoral edema. Recent advances in imaging technology have expanded the purview of neuroradiologists, who play an increasingly important role in meningioma diagnosis and management. Tumor vascularity can now be determined using arterial spin labeling and dynamic susceptibility contrast-enhanced sequences, allowing the neurosurgeon or neurointerventionalist to assess patient candidacy for preoperative embolization. Meningioma consistency can be inferred based on signal intensity; emerging machine learning technologies may soon allow radiologists to predict consistency long before the patient enters the operating room. Perfusion imaging coupled with magnetic resonance spectroscopy can be used to distinguish meningiomas from malignant meningioma mimics. In this comprehensive review, we describe key features of meningiomas that can be established through neuroimaging, including size, location, vascularity, consistency, and, in some cases, histologic grade. We also summarize the role of advanced imaging techniques, including magnetic resonance perfusion and spectroscopy, for the preoperative evaluation of meningiomas. In addition, we describe the potential impact of emerging technologies, such as artificial intelligence and machine learning, on meningioma diagnosis and management. A strong foundation of knowledge in the latest meningioma imaging techniques will allow the neuroradiologist to help optimize preoperative planning and improve patient outcomes.

Rethinking on the epidemic situation and standardized diagnosis and treatment of low risk differentiated thyroid cancer

Thyroid cancer is a malignant tumor originating from thyroid epithelial or parafollicular epithelial cells. It is also the most common malignant tumor in the head and neck. At present, the incidence of thyroid cancer ranks ninth among all common malignant tumors, and has become one of the top ten common malignant tumors. In recent years, with the release of various guidelines, the diagnosis and treatment of thyroid cancer around the world is gradually standardized. Meanwhile, China has also begun to implement quality control of diagnosis and treatment, standardize diagnosis and treatment behavior, and promote the standardization of diagnosis and treatment of thyroid tumors nationwide, in order to ultimately improve patient's survival rate and quality of life. Based on the current changes in the diagnosis and treatment of thyroid cancer at home and abroad, the article discusses the epidemic situation, diagnosis and treatment status, new concept and progress of standardized diagnosis and treatment of thyroid cancer.

Advances in the multidisciplinary surgical approach to primary spinal sarcomas: insights from a retrospective case series on outcomes and survival

IntroductionThe management of spinal sarcomas is complex, given their widespread involvement and high recurrence rates. Despite consensus on the need for a multidisciplinary approach with surgery at its core, there is a lack of definitive guidelines for clinical decision-making. This study examines a case series of primary spinal sarcomas, focusing on the surgical strategies, clinical results, and survival data to inform and guide therapeutic practices.MethodsWe conducted a retrospective analysis of patients who underwent surgical resection for primary spinal sarcomas between 2005 and 2022. The study focused on gathering data on patient demographics, surgical details, postoperative complications, overall hospital stay, and mortality within 90 days post-surgery.ResultsThe study included 14 patients with a primary diagnosis of spinal sarcoma, with an average age of 48.6 ± 12.6 years. Chondrosarcoma emerged as the most common tumor type, representing 57.1% of cases, followed by Ewing sarcoma at 35.7%, and synovial sarcoma at 7.1%. Patients with chondrosarcoma were treated with en-bloc resection, while the patient with synovial sarcoma underwent intra-lesional excision and those with Ewing sarcoma received decompression and tumor debulking. Postoperative assessments revealed significant improvements in neurological conditions. Notably, functional status as measured by the Karnofski Performance Index (KPI), improved substantially post-surgery (from 61.4 to 80.0%) The mean follow-up was 34.9 ± 9.2 months. During this time period one patient experienced fatal bleeding after en-bloc resection complications involving the vena cava. None of the patient needed further surgery.ConclusionsOur 16-year study offers vital insights into managing primary spinal sarcomas, showcasing the effectiveness of surgical intervention, particularly en-bloc resection. Despite their rarity and complexity, our multidisciplinary treatment approach yields improved outcomes and highlights the potential for refined surgical strategies to become standardized care in this challenging domain.

Rib tumors: A ten-year institutional study

Objectives The primary aim of this study was to study the demography and frequency distribution of the various rib tumors. The treatment modality offered and patient outcomes were also recorded wherever available. Material and Methods A ten year data was retrieved from the hospital registry from 2011-2021. Inclusion criteria were all patients with any tumors in the rib. Those patients who did not have a histological diagnosis and those having a chest wall mass and secondary involvement of the ribs were excluded. Results Out of 72 cases of rib tumors, 25 were diagnosed as Ewing Sarcoma, 22 Chondrosarcoma cases, 10 Multiple myeloma/plasmacytoma cases, 9 Osteosarcoma cases, rest 1 case each of Non Hodgkin Lymphoma, Brown tumor, Enchondroma, Osteochondroma, Clear cell sarcoma and metastases. Conclusion In this study the most common primary malignant tumor of the ribs in adults was Chondrosarcoma (41.1%) and in pediatric & young adolescent age group (upto 18yrs) it was Ewing sarcoma (76.1%)

Predicting telomerase reverse transcriptase promoter mutation in glioma: A systematic review and diagnostic meta-analysis on machine learning algorithms.

Glioma is one of the most common primary brain tumors. The presence of the telomerase reverse transcriptase promoter (pTERT) mutation is associated with a better prognosis. This study aims to investigate the TERT mutation in patients with glioma using machine learning (ML) algorithms on radiographic imaging. This study was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The electronic databases of PubMed, Embase, Scopus, and Web of Science were searched from inception to August 1, 2023. The statistical analysis was performed using the MIDAS package of STATA v.17. A total of 22 studies involving 5371 patients were included for data extraction, with data synthesis based on 11 reports. The analysis revealed a pooled sensitivity of 0.86 (95% CI: 0.78-0.92) and a specificity of 0.80 (95% CI 0.72-0.86). The positive and negative likelihood ratios were 4.23 (95% CI: 2.99-5.99) and 0.18 (95% CI: 0.11-0.29), respectively. The pooled diagnostic score was 3.18 (95% CI: 2.45-3.91), with a diagnostic odds ratio 24.08 (95% CI: 11.63-49.87). The Summary Receiver Operating Characteristic (SROC) curve had an area under the curve (AUC) of 0.89 (95% CI: 0.86-0.91). The study suggests that ML can predict TERT mutation status in glioma patients. ML models showed high sensitivity (0.86) and moderate specificity (0.80), aiding disease prognosis and treatment planning. However, further development and improvement of ML models are necessary for better performance metrics and increased reliability in clinical practice.

Hospital frailty risk score predicts high-value care outcomes following brain metastasis resection

ObjectiveBrain metastases (BM) are the most common adult intracranial tumors, representing a significant source of morbidity in patients with systemic malignancy. Frailty indices, including 11- and 5-factor modified frailty indices (mFI-11 and mFI-5), American Society of Anesthesiologists (ASA) physical status classification, and Charlson Comorbidity Index (CCI), have recently demonstrated an important role in predicting high-value care outcomes in neurosurgery. This study aims to investigate the efficacy of the newly developed Hospital Frailty Risk Score (HFRS) on postoperative outcomes in BM patients. MethodsAdult patients with BM treated surgically at a single institution were identified (2017–2019). HFRS was calculated using ICD-10 codes, and patients were subsequently separated into low (<5), intermediate (5−15), and high (>15) HFRS cohorts. Multivariate logistic regressions were utilized to identify associations between HFRS and complications, length of stay (LOS), hospital charges, and discharge disposition. Model discrimination was assessed using receiver operating characteristic (ROC) curves. ResultsA total of 356 patients (mean age: 61.81±11.63 years; 50.6 % female) were included. The mean±SD for HFRS, mFI-11, mFI-5, ASA, and CCI were 6.46±5.73, 1.31±1.24, 0.95±0.86, 2.94±0.48, and 8.69±2.07, respectively. On multivariate analysis, higher HFRS was significantly associated with greater complication rate (OR=1.10, p<0.001), extended LOS (OR=1.13, p<0.001), high hospital charges (OR=1.14, p<0.001), and nonroutine discharge disposition (OR=1.12, p<0.001), and comparing the ROC curves of mFI-11, mFI-5, ASA,and CCI, the predictive accuracy of HFRS was the most superior for all four outcomes assessed. ConclusionThe predictive ability of HFRS on BM resection outcomes may be superior than other frailty indices, offering a new avenue for routine preoperative frailty assessment and for managing postoperative expectations.

The effect of surgical access on functional and oncological results of resections in laryngeal cancer T2N0M0

Introduction. Laryngeal cancer is the most common malignant neoplasm of the ENT organs. The preferred and primary therapy for this pathology is surgical intervention. The search for highly effective organ-saving methods of surgical treatment aimed at minimization of resection volume and preservation of functioning of the larynx continues. Current endolaryngeal surgery allows to improve functional results and is the most modern and advanced method.Aim. To compare functional and oncological results of surgical treatment of patients with laryngeal squamous cell carcinoma Т2N0M0 performed through transcervical and endolaryngeal accesses.Materials and methods. The results of surgical treatment of patients with squamous cell carcinoma of the vocal folds part of the larynx T2N0M0 performed between 2015 and 2020 at the Oncological Division of Head and Neck Tumors of the The National Medical Research Center for Otorhinolaryngology of the Federal Medico-Biological Agency of Russia were analyzed. The study included 49 men aged 52–72 years; the diagnosis was confirmed by histological examination. All patients underwent standard exams which led to diagnosis per the Tumor, Nodus and Metastasis international system.Results. Three-year recurrence-free survival after endolaryngeal resection of cancer of the vocal folds part of the larynx Т2N0M0 was 88.47 %, after transcervical resections it was 91.31 %. Analysis of functional and surgical results showed that compared to patients who underwent surgery through external access, in patients who underwent surgery with endolaryngeal access the rate of complications associated with the surgical wound in the early postoperative period was 13.04 % lower, frequency of cicatricial stenoses of the larynx was 20.06 % lower, and abnormalities of separating function of the larynx were 49.33 % rarer.Conclusion. In patients who underwent endolaryngeal resection of the larynx, better functional and surgical results were achieved compared to patients who underwent surgery through external access. Moreover, there was no statistically significant difference in oncological results between the study groups. This allows to conclude that minimally invasive endolaryngeal approaches are highly effective and functional in organ-saving surgeries for patients with squamous cell carcinoma of the vocal fold part of the larynx T2N0M0.

Bromelain-facilitated GNPs: A strategic innate anticancer delivery system for methotrexate into osteosarcoma cells

Osteosarcoma is the most common malignant bone tumor in children and adolescents during rapid bone growth. Traditional chemotherapy has markedly improved patient outcomes but suffers from nonspecific side effects due to nonspecific drug distribution, highlighting the need for targeted therapies. Methotrexate, although effective, poses toxicity concerns and prompts exploration into advanced drug delivery systems like nanoparticles. Here, we developed a novel method of synthesizing gold nanoparticles using bromelain (G-BNPs) as a reducing and capping agent, and we conjugated G-BNPs with methotrexate (G-B-MNPs) via 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide (EDC/NHS) as crosslinker. Our meticulous characterization, which included UV–visible spectroscopy, Transmission electron microscopy (TEM), Dynamic light scattering (DLS), Zeta potential, and Fourier-transform infrared spectroscopy (FTIR) analyses confirmed the successful fabrication and drug conjugation of the G-BNPs. We then evaluated the cytotoxicity of the G-BNPs (sized ∼ 21 nm) and G-B-MNPs (sized ∼ 24 nm) on the osteosarcoma cell lines, Saos-2 and MG-63, as well as the non-cancerous primary osteoblast cells. Our findings revealed that G-B-MNPs significantly increased the cytotoxic impact on osteosarcoma cells compared to methotrexate alone while showing minimal toxicity toward primary osteoblast cells. Importantly, using 4`,6-diamidino-2-phenylindole(DAPI), we demonstrated that G-B-MNPs were delivered directly into the nucleus of the cells without encountering lysosomes. G-B-MNPs can be considered a potential drug delivery method for osteosarcoma treatment by improving effectiveness and reducing adverse effects, thereby enhancing patient prognosis.

Epidemiological trends and treatment abandonment of paediatric solid tumours in a nigerian tertiary hospital: a seven-year review (2016–2022)

BackgroundPaediatric solid tumours, both benign and malignant, present significant health challenges, particularly in Sub-Saharan Africa where comprehensive data is limited. This study aims to elucidate the prevalence, distribution, and treatment outcomes of paediatric solid neoplasms in a tertiary hospital in South-East Nigeria over a seven-year period.MethodsA retrospective cohort study was conducted at Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, Nigeria. Clinical details and histological slides of confirmed cases from January 2016 to December 2022 were reviewed. Data extraction focused on socio-demographic variables and treatment outcomes, analysed using statistical methods.ResultsThe study included 293 children diagnosed with solid tumours (58.1% malignant, 41.9% benign), with a female predominance (61.8%). The median age at diagnosis was 12 years. Fibroadenoma was the most common benign tumour (61.8% of benign cases), while non-Hodgkin lymphoma was the predominant malignant tumour (18.2% of malignant cases). Treatment abandonment rates differed significantly between benign (13.8%) and malignant (51.2%) tumours. Significant associations were found between treatment outcomes and factors such as gender (p = 0.0001 for benign tumours), age category (p = 0.0001 for benign tumours), and specific diagnoses (p = 0.0001 for both benign and malignant tumours).ConclusionThis study underscores the substantial burden of paediatric solid tumours in South-East Nigeria and highlights the critical need for improved treatment adherence strategies, particularly for malignant cases. The findings emphasize the importance of tailored interventions based on tumour type, age, and gender. These insights can inform future research, policy formulation, and healthcare strategies aimed at enhancing the management and outcomes of paediatric solid neoplasms in resource-limited settings.

In Situ Colorimetric LAMP Based on One-Step Modified Filter Paper to Screen Human Papillomavirus (HPV)16/18 from Clinical Samples.

Cervical cancer is among the most common malignant tumors in women. The development of rapid screening techniques plays an important role in early screening for cancer treatment. We have developed an HPV screening method, which effectively combines the high-efficiency nucleic acid enrichment of chitosan-modified filter paper and the rapid visual detectability of colorimetric LAMP, along with the enhancement of the tolerance ability of the pH-sensitive LAMP reagent to acidic original samples, making the detection of HPV 16/18 easy to carry out and reliable, which is helpful for the epidemiological prevention and control strategies of HPV-induced cancer. This technique can simultaneously exhibit the "in situ amplification" capability of chitosan-modified filter paper and the nontemperature cycle dependence of visual LAMP detection. Therefore, DNA extraction and amplification can be performed efficiently and quickly within a single reaction where all DNA is concentrated in the QF paper disc. By embedding amino-modified filter paper into the plastic chip, a simple and reliable disposable chip was prepared for rapid HPV16 and HPV18 detection from clinical endometrial samples, and the results were 100% consistent with clinical diagnosis. More importantly, even after the sample was diluted 100-fold, HPV16/18-infected cells could be accurately identified, showing the advantages of the system in early cancer screening. Moreover, for endometrial samples containing plenty of cells, the filter paper could be used to enrich cells by filtration, preventing the acidic fluid from impacting pH-induced colorimetric LAMP detection and realizing direct amplification for HPV identification without nucleic acid extraction. This easy-to-operate system that can analyze a wide range of samples will be suitable for routine on-site HPV screening, dramatically extending the applications and utility for rapid, near-patient nucleic acid testing.

Lung Cancer Adoptive Cell Therapy: Inspiring TIL ACT Comes Center Stage.

Schoenfeld and colleagues report, in this issue, a measurable objective response rate in 6/28 (21.4%) of patients with advanced non-small cell lung cancer treated with lifileucel, a cell therapy product based on autologous tumor-infiltrating lymphocytes (TIL). Extending solid evidence in advanced melanoma that led to FDA approval of lifileucel, this new evidence bodes well for treating patients with other common tumor histologies, justifying important efforts by a large number of academic and biotechnology companies engaged in improving the TIL process. See related article by Schoenfeld et al., p. 1389 (1).

Low NDRG2, regulated by the MYC/MIZ-1 complex and methylation, predicts poor outcomes in DLBCL patients.

Diffuse large B-cell lymphoma (DLBCL) represents the most common tumor in non-Hodgkin's lymphoma. N-Myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor highly expressed in healthy tissues but downregulated in many cancers. Although cell proliferation-related metabolism rewiring has been well characterized, less is known about the mechanism of metabolic changes with DLBCL. Herein, we investigated the expressions of NDRG2, MYC and Myc-interacting zinc finger protein 1 (MIZ-1) in seven human lymphoma (mostly DLBCLs) cell lines. NDRG2 expression was inversely correlated with the expressions of MYC and MIZ-1. Further, we explored the regulatory mechanism and biological functions underlying the lymphomagenesis involving NDRG2, MYC and MIZ-1. MYC and MIZ-1 promoted DLBCL cell proliferation, while NDRG2 induced apoptosis in LY8 cells. Moreover, NDRG2 methylation was reversed by the 5-Aza-2'-deoxycytidine (5-Aza-CDR) treatment, triggering the downregulation of MYC and inhibiting DLBCL cell survival. MYC interacts with NDRG2 to regulate energy metabolism associated with mTOR. Remarkably, supporting the biological significance, the converse correlation between NDRG2 and MYC was observed in human DLBCL tumor tissues (R = -0.557). Bioinformatics analysis further validated the association among NDRG2, MYC, MIZ-1, mTOR, and related metabolism genes. Additionally, NDRG2 (P = 0.001) and MYC (P < 0.001) were identified as promising prognostic biomarkers in DLBCL patients through survival analysis. Together, our data demonstrate that the MYC/MIZ-1 complex interplays with NDRG2 to influence the proliferation and apoptosis of DLBCL cells and show the characterizations of NDRG2, MYC and MIZ-1 for metabolism features and prediction prognosis in DLBCL.

Suicide among patients with oral cancer: A population-based study

BackgroundPatients with oral cancer usually experience disfigurement and dysfunction which are shared risk factors of suicide. The aim of the study was to comprehensively assess the characteristics of suicide and risk factors for suicide in patients with oral cancer. MethodsSurveillance, Epidemiology, and End Results database was used to acquire information of patients with common malignant tumors including oral cancer from 1975 to 2020. The aim was to explore the incidence of suicide, and timing of suicide among patients with oral cancer. A Fine-Gray competing risks regression model was employed to analyze risk factors associated with suicide among patients with various demographic and tumor characteristics. ResultsTotally, 7685 patients with different malignant tumors committed suicide. Among them, 203 patients with oral cancer died due to suicide, presenting a suicide rate of 54.5/100,000 person-years, which was almost 3.5 times that of the US general population and 1.5 times that of the overall US patients with cancer in our study. Approximately 18 %, 40 %, and 55 % of suicides occurred in first year, first 3 years, and first 5 years after diagnosis. Being male, White race, and having a single primary tumor might be regarded as the risk factors for suicide. ConclusionAs oral cavity is closely associated with appearance, pronunciation and ingestion, patients with oral cancer have a significant high risk of suicide. Tremendous attention needs to be paid to patients with oral cancer particularly those exhibiting characteristics associated with a high risk of suicide.

Comprehensive clinical imaging, histopathological analysis and liquid biopsy-based surveillance of human uveal melanoma in a prolonged rabbit xenograft model.

Uveal melanoma is the most common intraocular tumor in adults. Our group has previously developed a human uveal melanoma animal model; however, adverse effects caused by the immunosuppressive agent, cyclosporine A, prevented animals from surviving more than 12 weeks. In this study, we tested multiple cyclosporine A doses over an extended disease course up to 20 weeks, providing complete clinical imaging of intraocular tumors, histopathological analysis and liquid biopsy biomarker analysis. Twenty albino rabbits were divided into four groups with different daily cyclosporine A schedules (0-10 mg/kg) and inoculated with human uveal melanoma cell lines, 92.1 or MP41, into the suprachoroidal space. Rabbits were monitored with fundoscopy, ultrasound and optical coherence tomography. Intraocular tumors (macroscopic or microscopic) were detected in all study animals. Tumor size and growth were correlated to cyclosporine A dose, with tumors regressing when cyclosporine A was arrested. All tumors expressed HMB-45 and MelanA; however, tumor size, pigmentation and cell morphology differed in 92.1 vs. MP41 tumors. Finally, across all groups, circulating tumor DNA from plasma and aqueous humor was detected earlier than tumor detection by imaging and correlated to tumor growth. In conclusion, using three clinically relevant imaging modalities (fundoscopy, ultrasonography and optical coherence tomography) and liquid biopsy, we were successfully able to monitor tumor progression in our rabbit xenograft model of human uveal melanoma.

IMPDH2 suppression impedes cell proliferation by instigating cell cycle arrest and stimulates apoptosis in pediatric hepatoblastoma

BackgroundHepatoblastoma (HB) is the most common pediatric liver tumor, presenting significant therapeutic challenges due to its high rates of recurrence and metastasis. While Inosine Monophosphate Dehydrogenase 2(IMPDH2) has been associated with cancer progression, its specific role and clinical implications in HB have not been fully elucidated.MethodsThis study utilized Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Tissue Microarray (TMA) for validation. Following this, IMPDH2 was suppressed, and a series of in vitro assays were conducted. Flow cytometry was employed to assess apoptosis and cell cycle arrest. Additionally, the study explored the synergistic therapeutic effects of mycophenolate mofetil (MMF) and doxorubicin (DOX) on HB cell lines.ResultsThe study identified a marked overexpression of IMPDH2 in HB tissues, which was strongly correlated with reduced Overall Survival (OS) and Event-Free Survival (EFS). IMPDH2 upregulation was also found to be associated with key clinical-pathological features, including pre-chemotherapy alpha-fetoprotein (AFP) levels, presence of preoperative metastasis, and the pre-treatment extent of tumor (PRETEXT) staging system. Knockdown of IMPDH2 significantly inhibited HB cell proliferation and tumorigenicity, inducing cell cycle arrest at the G0/G1 phase. Notably, the combination of MMF, identified as a specific IMPDH2 inhibitor, with DOX, substantially enhanced the therapeutic response.ConclusionThe overexpression of IMPDH2 was closely linked to adverse outcomes in HB patients and appeared to accelerate cell cycle progression. These findings suggest that IMPDH2 may serve as a valuable prognostic indicator and a potential therapeutic target for HB.ImpactThe present study unveiled a significant overexpression of inosine monophosphate dehydrogenase 2 (IMPDH2) in hepatoblastoma (HB) tissues, particularly in association with metastasis and recurrence of the disease. The pronounced upregulation of IMPDH2 was found to be intimately correlated with adverse outcomes in HB patients. This overexpression appears to accelerate the progression of the cell cycle, suggesting that IMPDH2 may serve as a promising candidate for both a prognostic marker and a therapeutic target in the context of HB.

Silencing PDCD4 Mediates Transcription Factor EB Overexpression Promoting Proliferation, Migration, and Invasion of Cervical Cancer Hela Cells

Cervical cancer is a common gynecologic malignant tumor, the occurrence and development of which are related to multiple genetic and environmental factors. Recent studies have shown that Programmed Cell Death 4 (PDCD4) plays a crucial role in cervical cancer, and that silencing PDCD4 mediates Transcription Factor EB (TFEB) overexpression, promoting cell proliferation, migration, and invasion in this disease. This study utilized the Hela cell line as a cervical cancer model to investigate the changes in TFEB expression levels and the proliferation, migration, invasion, and EMT processes of cervical cancer cells through the silencing of PDCD4. Real-time quantitative PCR and Western blot were employed to assess the expression levels of PDCD4 and TFEB, while CCK-8, scratch assay, Transwell invasion assay, and Western blot were used to evaluate changes in cell proliferation, migration, invasion capabilities, and EMT processes. The experimental results demonstrated that silencing PDCD4 significantly increased the expression level of TFEB. Simultaneously, silencing PDCD4 also significantly accelerated the proliferation rate of Hela cells, enhanced the cells’ migration, invasion capabilities, and promoted the EMT processes. Further experimental results showed that silencing TFEB could partially reverse the promoting effects of PDCD4 silencing on cell proliferation, migration, and invasion. In cervical cancer, silencing PDCD4 can lead to TFEB overexpression, thereby promoting the proliferation, migration, and invasion of Hela cells. These findings provide crucial clues for the in-depth study of molecular mechanisms in cervical cancer and indicate that the PDCD4-TFEB pathway could potentially serve as a target for the treatment and prevention of this disease.

Decreased expression of p53 is associated with down expression of zyxin in breast cancer.

Breast cancer (BC) is considered one of the most common malignant tumors leading to death in women, and genetic factors have a crucial role in BC pathogenesis. Zyxin (ZYX) is one of these factors that may be important in p53 level and function. Thus, the present work aimed to investigate the ZYX gene and protein expression in tumor tissue and matched margin tissue and its correlation with the p53 expression. In a present case-control study, 30 tumors and 30 matched margin tissues were obtained from Iran Tumor Bank/Tehran University of Medical Sciences. Real-time polymerase chain reaction and western blot analysis techniques were applied to evaluate the genes and protein expression, respectively. The data showed that expression of the ZYX gene in tumor tissues significantly decreased (p = 0.0274) compared to matched margin tissues. In contrast, the p53 gene expression in tumor tissues had no significant difference with matched margin tissues. Additionally, we observed that ZYX and p53 genes expression in tumor tissues of estrogen receptor-positive patients had significant elevation than estrogen receptor-negative patients (p < 0.001, p < 0.001, respectively). The data of the western blot analysis technique showed that protein expression of ZYX (p = 0.0024) and P53 protein (p = 0.0218) in tumor tissues was significantly reduced compared to matched margin tissues. Additionally, our analysis showed a direct and significant correlation between the expression of ZYX and p53 proteins (r = 0.7797, p = 0.0126) and expression of ZYX and p53 genes (r = 0.3079, p = 0.0187). Based on our observation, ZYX might have a tumor suppressor role and is associated with p53.

Identification and Validation of a Novel Tertiary Lymphoid Structures-Related Prognostic Gene Signature in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors originating from the digestive system. Tertiary lymphoid structures (TLS), non-lymphoid tissues outside of the lymphoid organs, are closely connected to chronic inflammation and tumorigenesis. However, the detailed relationship between TLS and HCC prognosis remained unclear. In this study, we aimed to construct a TLS-related gene signature for predicting the prognosis of HCC patients. The Cancer Genome Atlas (TCGA) clinical data from 369 HCC tissues and 50 normal liver tissues were utilized to examine the differential expression of TLS-related genes. Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort. The Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Furthermore, Cox regression analysis was applied to identify whether the TLS score could be employed as an independent prognosis factor. A nomogram was developed to predict the survival probability of HCC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for TLS-related genes. Genetic mutation analysis, the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA) were used to assess the tumor mutation landscape and immune infiltration. Finally, the role of the TLS score in HCC therapy was investigated. Six genes were included in the construction of our prognostic model (CETP, DNASE1L3, PLAC8, SKAP1, C7, and VNN2), and we validated its accuracy. Survival analysis showed that patients in the high-TLS score group had a significantly better overall survival than those in the low-TLS score group. Univariate, multivariate Cox regression analysis and the establishment of a nomogram indicated that the TLS score could independently function as a potential prognostic marker. A significant association between TLS score and immunity was revealed by an analysis of gene alterations and immune cell infiltration. In addition, two subtypes of the TLS score could accurately predict the effectiveness of sorafenib, transcatheter arterial chemoembolization (TACE), and immunotherapy in HCC patients. In this research, we conducted and validated a prognostic model associated with TLS that may be helpful for predicting clinical outcomes and treatment responsiveness for HCC patients.

HAS2 facilitates glioma cell malignancy and suppresses ferroptosis in an FZD7-dependent manner.

Glioma is the most common malignant tumor in the central nervous system, and it is crucial to uncover the factors that influence prognosis. In this study, we utilized Mfuzz to identify a gene set that showed a negative correlation with overall survival in patients with glioma. Gene Ontology (GO) enrichment analyses were then undertaken to gain insights into the functional characteristics and pathways associated with these genes. The expression distribution of Hyaluronan Synthase 2 (HAS2) was explored across multiple datasets, revealing its expression patterns. Invitro and invivo experiments were carried out through gene knockdown and overexpression to validate the functionality of HAS2. Potential upstream transcription factors of HAS2 were predicted using transcriptional regulatory databases, and these predictions were experimentally validated using ChIP-PCR and dual-luciferase reporter gene assays. The results showed that elevated expression of HAS2 in glioma indicates poor prognosis. HAS2 was found to play a role in activating an antiferroptosis pathway in glioma cells. Inhibiting HAS2 significantly increased cellular sensitivity to ferroptosis-inducing agents. Finally, we determined that the oncogenic effect of HAS2 is mediated by the key receptor of the WNT pathway, FZD7.