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Cancer Medicine May 2024The goal of this study was to create a nomogram using routine parameters to predict leptomeningeal metastases (LMs) in advanced lung adenocarcinoma (LAC) patients to...
BACKGROUND
The goal of this study was to create a nomogram using routine parameters to predict leptomeningeal metastases (LMs) in advanced lung adenocarcinoma (LAC) patients to prevent needless exams or lumbar punctures and to assist in accurately diagnosing LMs.
METHODS
Two hundred and seventy-three patients with LMs and brain metastases were retrospectively reviewed and divided into derivation (n = 191) and validation (n = 82) cohorts using a 3:7 random allocation. All LAC patients with LMs had positive cerebrospinal fluid cytology results and brain metastases confirmed by magnetic resonance imaging. Binary logistic regression with backward stepwise selection was used to identify significant characteristics. A predictive nomogram based on the logistic model was assessed through receiver operating characteristic curves. The validation cohort and Hosmer-Lemeshow test were used for internal validation of the nomogram.
RESULTS
Five clinicopathological parameters, namely, gene mutations, surgery at the primary lung cancer site, clinical symptoms of the head, N stage, and therapeutic strategy, were used as predictors of LMs. The area under the curve was 0.946 (95% CI 0.912-0.979) for the training cohort and 0.861 (95% CI 0.761-0.961) for the internal validation cohort. There was no significant difference in performance between the two cohorts (p = 0.116). In the internal validation, calibration plots revealed that the nomogram predictions were well suited to the actual outcomes.
CONCLUSIONS
We created a user-friendly nomogram to predict LMs in advanced lung cancer patients, which could help guide treatment decisions and reduce unnecessary lumbar punctures.
Topics: Humans; Nomograms; Male; Female; Middle Aged; Adenocarcinoma of Lung; Lung Neoplasms; Retrospective Studies; Aged; Lymphatic Metastasis; Meningeal Neoplasms; Adult; Brain Neoplasms; ROC Curve; Magnetic Resonance Imaging
PubMed: 38686619
DOI: 10.1002/cam4.7206 -
Environment International May 2024Some have looked forward to the publication of the results of the COSMOS study on brain tumors, because the potential biases from retrospective investigations...
Some have looked forward to the publication of the results of the COSMOS study on brain tumors, because the potential biases from retrospective investigations predominating the search for brain tumor risks of mobile phone use since the late 1990 s were deemed unresolvable by further investigations of that type. Indeed, prospective cohort studies typically have the advantage of being not or less affected by differential exposure misclassification, recall and selection bias, and, as they proceed in the direction of the time arrow, results are more easily interpreted in terms of causation. However, results of the COSMOS study published now in this journal are not of help for the risk assessment of mobile phone use and do not support the conclusions of the authors that their findings "suggest that the cumulative amount of mobile phone use is not associated with the risk of developing glioma, meningioma, or acoustic neuroma".
Topics: Brain Neoplasms; Humans; Cell Phone; Prospective Studies; Cohort Studies; Bias; Risk Assessment; Glioma; Meningioma; Neuroma, Acoustic; Radiation Exposure; Young Adult; Adult; Middle Aged; Aged
PubMed: 38677087
DOI: 10.1016/j.envint.2024.108665 -
Medicina (Kaunas, Lithuania) Mar 2024In our study, we document the case of a 48-year-old patient who presented at our clinic with various neurological disturbances. Magnetic Resonance Imaging revealed the... (Review)
Review
In our study, we document the case of a 48-year-old patient who presented at our clinic with various neurological disturbances. Magnetic Resonance Imaging revealed the presence of an intraventricular meningioma located in the body of the left lateral ventricle measuring 60 mm in diameter. This tumor was classified as a giant meningioma, accompanied by a significant amount of digitiform-type edema. A surgical procedure was conducted, resulting in a gross total resection of the tumor. Histopathological analysis identified the tumor as a fibrous meningioma. Postoperative assessments, as well as follow-ups conducted at 3 months and 1 year post-surgery, indicated considerable neurological improvement. The patient exhibited a remission of hemiparesis and gait disturbances along with a marginal improvement in the status of expressive aphasia. This case report underscores the significance of achieving total and safe resection of the tumor and includes an analysis of various cases from the literature, particularly focusing on those that describe minimally invasive surgical approaches and highlight the benefits of radiosurgery in the treatment of giant intraventricular meningiomas.
Topics: Female; Humans; Middle Aged; Cerebral Ventricle Neoplasms; Magnetic Resonance Imaging; Meningeal Neoplasms; Meningioma; Treatment Outcome
PubMed: 38674205
DOI: 10.3390/medicina60040560 -
International Journal of Molecular... Apr 2024Medulloblastoma (MB) encompasses diverse subgroups, and leptomeningeal disease/metastasis (LMD) plays a substantial role in associated fatalities. Despite extensive...
Medulloblastoma (MB) encompasses diverse subgroups, and leptomeningeal disease/metastasis (LMD) plays a substantial role in associated fatalities. Despite extensive exploration of canonical genes in MB, the molecular mechanisms underlying LMD and the involvement of the orthodenticle homeobox 2 (OTX2) gene, a key driver in aggressive MB Group 3, remain insufficiently understood. Recognizing OTX2's pivotal role, we investigated its potential as a catalyst for aggressive cellular behaviors, including migration, invasion, and metastasis. OTX2 overexpression heightened cell growth, motility, and polarization in Group 3 MB cells. Orthotopic implantation of OTX2-overexpressing cells in mice led to reduced median survival, accompanied by the development of spinal cord and brain metastases. Mechanistically, OTX2 acted as a transcriptional activator of the Mechanistic Target of Rapamycin (mTOR) gene's promoter and the mTORC2 signaling pathway, correlating with upregulated downstream genes that orchestrate cell motility and migration. Knockdown of mTOR mRNA mitigated OTX2-mediated enhancements in cell motility and polarization. Analysis of human MB tumor samples (N = 952) revealed a positive correlation between OTX2 and mTOR mRNA expression, emphasizing the clinical significance of OTX2's role in the mTORC2 pathway. Our results reveal that OTX2 governs the mTORC2 signaling pathway, instigating LMD in Group 3 MBs and offering insights into potential therapeutic avenues through mTORC2 inhibition.
Topics: Animals; Female; Humans; Male; Mice; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cerebellar Neoplasms; Gene Expression Regulation, Neoplastic; Mechanistic Target of Rapamycin Complex 2; Medulloblastoma; Meningeal Neoplasms; Otx Transcription Factors; Signal Transduction
PubMed: 38674001
DOI: 10.3390/ijms25084416 -
International Journal of Molecular... Apr 2024Meningiomas are tumors of the central nervous system that vary in their presentation, ranging from benign and slow-growing to highly aggressive. The standard method for... (Review)
Review
Meningiomas are tumors of the central nervous system that vary in their presentation, ranging from benign and slow-growing to highly aggressive. The standard method for diagnosing and classifying meningiomas involves invasive surgery and can fail to provide accurate prognostic information. Liquid biopsy methods, which exploit circulating tumor biomarkers such as DNA, extracellular vesicles, micro-RNA, proteins, and more, offer a non-invasive and dynamic approach for tumor classification, prognostication, and evaluating treatment response. Currently, a clinically approved liquid biopsy test for meningiomas does not exist. This review provides a discussion of current research and the challenges of implementing liquid biopsy techniques for advancing meningioma patient care.
Topics: Humans; Meningioma; Liquid Biopsy; Biomarkers, Tumor; Meningeal Neoplasms; Extracellular Vesicles; Prognosis
PubMed: 38673779
DOI: 10.3390/ijms25084195 -
International Journal of Surgery... Apr 2024
Topics: Humans; Meningioma; Retrospective Studies; Meningeal Neoplasms; Male; Female; Cohort Studies
PubMed: 38668675
DOI: 10.1097/JS9.0000000000001364 -
Aging Apr 2024Some preceding researches have observed that certain neurological disorders, such as Alzheimer's disease and multiple sclerosis, may affect breast cancer risk. However,...
BACKGROUND
Some preceding researches have observed that certain neurological disorders, such as Alzheimer's disease and multiple sclerosis, may affect breast cancer risk. However, whether there are causal relationships between these neurological conditions and breast cancer is inconclusive. This study was designed to explore whether neurological disorders affected the risks of breast cancer overall and of the two subtypes (ER+ and ER-).
METHODS
In the course of this study, genome-wide association study (GWAS) data for nine neurological diseases (Alzheimer's disease, multiple sclerosis, Parkinson's disease, myasthenia gravis, generalized epilepsy, intracerebral haemorrhage, cerebral atherosclerosis, brain glioblastoma, and benign meningeal tumour) were collected from the Complex Trait Genetics lab and the MRC Integrative Epidemiology Unit, and single-nucleotide polymorphisms (SNPs) extensively associated with these neurological ailments had been recognized as instrumental variables (IVs). GWAS data on breast cancer were collected from the Breast Cancer Association Consortium (BCAC). Two-sample Mendelian randomization (MR) analyses as well as multivariable MR analyses were performed to determine whether these SNPs contributed to breast cancer risk. Additionally, the accuracy of the results was evaluated using the false discovery rate (FDR) multiple correction method. Both heterogeneity and pleiotropy were evaluated by analyzing sensitivities.
RESULTS
According to the results of two-sample MR analyses, Alzheimer's disease significantly reduced the risks of overall (OR 0.925, 95% CI [0.871-0.982], = 0.011) and ER+ (OR 0.912, 95% CI [0.853-0.975], = 0.007) breast cancer, but there was a negative result in ER- breast cancer. However, after multiple FDR corrections, the effect of Alzheimer's disease on overall breast cancer was not statistically significant. In contrast, multiple sclerosis significantly increased ER+ breast cancer risk (OR 1.007, 95% CI [1.003-1.011], = 0.001). In addition, the multivariable MR analyses showed that Alzheimer's disease significantly reduced the risk of ER+ breast cancer (IVW: OR 0.929, 95% CI [0.864-0.999], =0.047; MR-Egger: OR 0.916, 95% CI [0.846-0.992], =0.031); however, multiple sclerosis significantly increased the risk of ER+ breast cancer (IVW: OR 1.008, 95% CI [1.003-1.012], =4.35×10; MR-Egger: OR 1.008, 95% CI [1.003-1.012], =5.96×10). There were no significant associations between the remainder of the neurological diseases and breast cancer.
CONCLUSIONS
This study found the trends towards a decreased risk of ER+ breast cancer in patients with Alzheimer's disease and an increased risk in patients with multiple sclerosis. However, due to the limitations of Mendelian randomization, we cannot determine whether there are definite causal relationships between neurological diseases and breast cancer risk. For conclusive evidences, more prospective randomized controlled trials will be needed in the future.
Topics: Humans; Breast Neoplasms; Mendelian Randomization Analysis; Female; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Nervous System Diseases; Genetic Predisposition to Disease; Risk Factors; Alzheimer Disease
PubMed: 38663930
DOI: 10.18632/aging.205745 -
Journal of Neuro-oncology Jul 2024To identify the risk factors and management of the multiple recurrences and reoperations for intracranial meningiomas.
PURPOSE
To identify the risk factors and management of the multiple recurrences and reoperations for intracranial meningiomas.
METHODS
Data of a neurosurgical series of 35 patients reoperated on for recurrent intracranial meningiomas were reviewed. Analyzed factors include patient age and sex, tumor location, extent of resection, WHO grade, Ki67-MIB1 and PR expression at initial diagnosis, time to recurrence; pattern of regrowth, extent of resection, WHO grade and Ki67-MIB1 at first recurrence were also analyzed. All these factors were stratified into two groups based on single (Group A) and multiple reoperations (Group B).
RESULTS
Twenty-four patients (69%) belonged to group A and 11 (31%) to group B. The age < 65 years, male sex, incomplete resection at both initial surgery and first reoperation, and multicentric-diffuse pattern of regrowth at first recurrence are risk factors for multiple recurrences and reoperations. In group B, the WHO grade and Ki67-MIB1 increased in further recurrences in 54% and 64%, respectively. The time to recurrence was short in 7 cases (64%), whereas 4 patients (36%) further recurred after many years. Eight patients (73%) are still alive after 7 to 22 years and 2 to 4 reoperations.
CONCLUSION
The extent of resection and the multicentric-diffuse pattern of regrowth at first recurrence are the main risk factors for multiple recurrences and reoperations. Repeated reoperations might be considered even in patients with extensive recurrent tumors before the anaplastic transformation occurs. In such cases, even partial tumor resections followed by radiation therapy may allow long survival in good clinical conditions.
Topics: Humans; Meningioma; Male; Female; Middle Aged; Reoperation; Neoplasm Recurrence, Local; Adult; Aged; Meningeal Neoplasms; Ki-67 Antigen; Risk Factors; Retrospective Studies; Follow-Up Studies; Young Adult
PubMed: 38656725
DOI: 10.1007/s11060-024-04673-8 -
Turkish Neurosurgery 2024To highlight the diagnosis, follow-up, and treatment options for diffuse leptomeningeal glioneuronal tumor (DLGNT) by examining pediatric patients diagnosed with DLGNT...
AIM
To highlight the diagnosis, follow-up, and treatment options for diffuse leptomeningeal glioneuronal tumor (DLGNT) by examining pediatric patients diagnosed with DLGNT by molecular pathological evaluation and next generation sequencing at our center.
MATERIAL AND METHODS
In this retrospective analysis, patients diagnosed with DLGNT between January 2017 and December 2022 are outlined according to their demographic data, radiological data, pathology results, treatments, and follow-up data.
RESULTS
Four patients were diagnosed with DLGNT. All the patients were male. The mean age was 6.5 years. All but one patient had symptoms of increased intracranial pressure. An open biopsy was obtained from all patients for diagnosis. Three patients received radiotherapy and chemotherapy after the diagnosis. Two patients died during their follow-up, one of them in the early postoperative period. Two patients were clinically and radiologically stable in their follow-up after treatment.
CONCLUSION
Further work with larger cohorts is required to determine a common algorithm for DLGNT treatment and follow-up. This analysis may keep this entity in mind in patients with pediatric communicating hydrocephalus and may present insight into diagnosis, follow-up, and treatment options.
Topics: Humans; Male; Child; Meningeal Neoplasms; Retrospective Studies; Child, Preschool; Follow-Up Studies; Adolescent; Female
PubMed: 38650559
DOI: 10.5137/1019-5149.JTN.43742-23.2 -
BMC Cancer Apr 2024Leptomeningeal metastasis (LM) of small cell lung cancer (SCLC) is a highly detrimental occurrence associated with severe neurological disorders, lacking effective...
BACKGROUND
Leptomeningeal metastasis (LM) of small cell lung cancer (SCLC) is a highly detrimental occurrence associated with severe neurological disorders, lacking effective treatment currently. Proteolysis-targeting chimeric molecules (PROTACs) may provide new therapeutic avenues for treatment of podophyllotoxin derivatives-resistant SCLC with LM, warranting further exploration.
METHODS
The SCLC cell line H128 expressing luciferase were mutated by MNNG to generate H128-Mut cell line. After subcutaneous inoculation of H128-Mut into nude mice, H128-LM and H128-BPM (brain parenchymal metastasis) cell lines were primarily cultured from LM and BPM tissues individually, and employed to in vitro drug testing. The SCLC-LM mouse model was established by inoculating H128-LM into nude mice via carotid artery and subjected to in vivo drug testing. RNA-seq and immunoblotting were conducted to uncover the molecular targets for LM.
RESULTS
The SCLC-LM mouse model was successfully established, confirmed by in vivo live imaging and histological examination. The upregulated genes included EZH2, SLC44A4, VEGFA, etc. in both BPM and LM cells, while SLC44A4 was particularly upregulated in LM cells. When combined with PROTAC EZH2 degrader-1, the drug sensitivity of cisplatin, etoposide (VP16), and teniposide (VM26) for H128-LM was significantly increased in vitro. The in vivo drug trials with SCLC-LM mouse model demonstrated that PROTAC EZH2 degrader-1 plus VM26 or cisplatin/ VP16 inhibited H128-LM tumour significantly compared to VM26 or cisplatin/ VP16 alone (P < 0.01).
CONCLUSION
The SCLC-LM model effectively simulates the pathophysiological process of SCLC metastasis to the leptomeninges. PROTAC EZH2 degrader-1 overcomes chemoresistance in SCLC, suggesting its potential therapeutic value for SCLC LM.
Topics: Animals; Small Cell Lung Carcinoma; Mice; Humans; Lung Neoplasms; Drug Resistance, Neoplasm; Enhancer of Zeste Homolog 2 Protein; Podophyllotoxin; Cell Line, Tumor; Mice, Nude; Meningeal Carcinomatosis; Xenograft Model Antitumor Assays; Proteolysis
PubMed: 38644473
DOI: 10.1186/s12885-024-12244-3