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Gene expression-based analysis of extra-cerebral metastases of patients with cerebrotropism (defined here as development of brain metastasis within 6 months of stage IV disease), compared to patients who did not develop brain metastases for 18 months

ABSTRACT: To test the association between gene expression and cerebrotropism the Wilcoxon rank-sum test was utilized and revealed over 400 genes differentially expressed between thw two patient groups Please note that cerebrotropism is defined here as development of brain metastasis within < 6 months of stage IV disease In this study we utilized a well-annotated cohort of metastatic melanoma cases to acquire expression profiles of a total of 9,829 unique genes Cerebrotropism Status (provided in each sample characteristics field): 1 represents early cerebrotropic patients (patients who developed CNS metastases within 6 months of diagnosis of metastatic disease ) 0 represents non-cerebrotropic patients (patients who did not develop brain metastases for over 18 months.

ORGANISM(S): Homo sapiens

SUBMITTER: Parisi Fabio

PROVIDER: S-ECPF-GEOD-60464 | biostudies-other |

REPOSITORIES: biostudies-other

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Gene expression-based analysis of extra-cerebral metastases of patients with cerebrotropism (defined here as development of brain metastasis within < 6 months of stage IV disease), compared to patients who did not develop brain metastases for >18 months

2014-08-18 | GSE60464 | GEO

Project description:To test the association between gene expression and cerebrotropism the Wilcoxon rank-sum test was utilized and revealed over 400 genes differentially expressed between thw two patient groups Please note that cerebrotropism is defined here as development of brain metastasis within < 6 months of stage IV disease In this study we utilized a well-annotated cohort of metastatic melanoma cases to acquire expression profiles of a total of 9,829 unique genes Cerebrotropism Status (provided in each sample characteristics field): 1 represents early cerebrotropic patients (patients who developed CNS metastases within 6 months of diagnosis of metastatic disease ) 0 represents non-cerebrotropic patients (patients who did not develop brain metastases for over 18 months.

2014-08-18 | E-GEOD-60464 | biostudies-arrayexpress

Responses in the diffusivity and vascular function of the irradiated normal brain are seen up until 18 months following SRS of brain metastases.

Project description:BackgroundMRI may provide insights into longitudinal responses in the diffusivity and vascular function of the irradiated normal-appearing brain following stereotactic radiosurgery (SRS) of brain metastases.MethodsForty patients with brain metastases from non-small cell lung cancer (N = 26) and malignant melanoma (N = 14) received SRS (15-25 Gy). Longitudinal MRI was performed pre-SRS and at 3, 6, 9, 12, and 18 months post-SRS. Measures of tissue diffusivity and vascularity were assessed by diffusion-weighted and perfusion MRI, respectively. All maps were normalized to white matter receiving less than 1 Gy. Longitudinal responses were assessed in normal-appearing brain, excluding tumor and edema, in the LowDose (1-10 Gy) and HighDose (>10 Gy) regions. The Eastern Cooperative Oncology Group (ECOG) performance status was recorded pre-SRS.ResultsFollowing SRS, the diffusivity in the LowDose region increased continuously for 1 year (105.1% ± 6.2%; P < .001), before reversing toward pre-SRS levels at 18 months. Transient reductions in microvascular cerebral blood volume (P < .05), blood flow (P < .05), and vessel densities (P < .05) were observed in LowDose at 6-9 months post-SRS. Correspondingly, vessel calibers in LowDose transiently increased at 3-9 months (P < .01). The responses in HighDose displayed similar trends as in LowDose, but with larger interpatient variations. Vascular responses followed pre-SRS ECOG status.ConclusionsOur results imply that even low doses of radiation to normal-appearing brain following cerebral SRS induce increased diffusivity and reduced vascular function for up until 18 months. In particular, the vascular responses indicate the reduced ability of the normal-appearing brain tissue to form new capillaries. Assessing the potential long-term neurologic effects of SRS on the normal-appearing brain is warranted.

| S-EPMC7212876 | biostudies-literature

Outcome comparison of patients who develop leptomeningeal disease or distant brain recurrence after brain metastases resection cavity radiosurgery.

Project description:BackgroundTo compare the outcomes between patients with leptomeningeal disease (LMD) and distant brain recurrence (DBR) after stereotactic radiosurgery (SRS) brain metastases (BM) resection cavity.MethodsTwenty-nine patients having single-fraction SRS after BM resection who developed either LMD (n = 11) or DBR (n = 18) as their initial and only site of intracranial progression were retrospectively reviewed.ResultsPatients developing LMD more commonly had a metachronous presentation (91% vs 50%, P = .04) and recursive partitioning class 1 status (45% vs 6%, P = .02). There was no difference in the median time from SRS to the development of LMD or DBR (5.0 vs 3.8 months, P = .68). The majority of patients with LMD (10/11, 91%) developed the nodular variant (nLMD). Treatment for LMD was repeat SRS (n = 4), whole-brain radiation therapy (WBRT; n = 5), resection + WBRT (n = 1), and no treatment (n = 1). Treatment for DBR was repeat SRS (n = 9), WBRT (n = 3), resection + resection cavity SRS (n = 1), and no treatment (n = 5). Median overall survival (OS) from time of resection cavity SRS was 15.7 months in the LMD group and 12.7 months in the DBR group (P = .60), respectively. Median OS in salvage SRS and salvage WBRT were 25.4 and 5.0 months in the nLMD group (P = .004) while 18.7 and 16.2 months in the DBR group (P = .30), respectively.ConclusionsFollowing BM resection cavity SRS, nLMD recurrence is much more frequent than classical LMD. Salvage SRS may be considered for selected patients with nLMD, reserving salvage WBRT for patients with extensive intracranial disease without compromising survival. Further study with larger numbers of patients is needed.

| S-EPMC8034660 | biostudies-literature

(18)F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases.

Project description:PurposeWe report the biodistribution and radiation dosimetry of an integrin αvβ3 specific PET tracer (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2) (denoted as (18)F-Alfatide II). We also assessed the value of (18)F-Alfatide II in patients with brain metastases.MethodsA series of torso (from the skull to the thigh) static images were acquired in five healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45, and 60 min after injection of (18)F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with (18)F-FDG (5.55 MBq/kg) and (18)F-Alfatide II.ResultsInjection of (18)F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. (18)F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by (18)F-Alfatide II PET, while only ten lesions were visualized by (18)F-FDG, and 13 by CT.ConclusionF-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that (18)F-Alfatide II is feasible for human studies. (18)F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis.

| S-EPMC4626365 | biostudies-literature

Molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases.

Project description:BackgroundBrain metastases are a significant cause of mortality and morbidity for patients with melanoma. We hypothesize that the development of brain metastases may be explained by molecular heterogeneity between primary cutaneous melanoma (PCM) or extracranial (ECM) and brain (MBM) melanoma metastases.Materials and methodsWe compared next-generation sequencing, tumor mutational burden (TMB), and immunohistochemical staining for PD-L1 expression, among 132 MBM, 745 PCM, and 1190 ECM.ResultsThe most common genetic alterations among MBM included: BRAF (52.4%), NRAS (26.6%), CDKN2A (23.3%), NF1 (18.9%), TP53 (18%), ARID2 (13.8%), SETD2 (11.9%), and PBRM1 (7.5%). Four genes were found with higher frequency among MBM compared to PCM or ECM: BRAF (52.4% v 40.4% v 40.9%), SETD2 (11.9% v 1.9% v 3.9%), PBRM1 (7.5% v 1.6% v 2.6%), and DICER1 (4.4% v 0.6% v 0.4%). MBM showed higher TMB (p = .04) and higher PD-L1 expression (p = .002), compared to PCM. PD-L1 expression was slightly higher among MBM compared to ECM (p = .042), but there was no difference between TMB (p = .21).ConclusionsOur findings suggest a unique molecular profile for MBM, including higher rates of BRAF mutations, higher TMB and higher PD-L1 expression, and also implicate chromatin remodeling in the pathogenesis of MBM.

| S-EPMC7443369 | biostudies-literature

Detecting Tumor Metastases: The Road to Therapy Starts Here.

Project description:Metastasis is the complex process by which primary tumor cells migrate and establish secondary tumors in an adjacent or distant location in the body. Early detection of metastatic disease and effective therapeutic options for targeting these detected metastases remain impediments to effectively treating patients with advanced cancers. If metastatic lesions are identified early, patients might maximally benefit from effective early therapeutic interventions. Further, monitoring patients whose primary tumors are effectively treated for potential metastatic disease onset is also highly valuable. Finally, patients with metastatic disease can be monitored for efficacy of specific therapeutic interventions through effective metastatic detection techniques. Thus, being able to detect and visualize metastatic lesions is key and provides potential to greatly improve overall patient outcomes. In order to achieve these objectives, researchers have endeavored to mechanistically define the steps involved in the metastatic process as well as ways to effectively detect metastatic progression. We presently overview various preclinical and clinical in vitro and in vivo assays developed to more efficiently detect tumor metastases, which provides the foundation for developing more effective therapies for this invariably fatal component of the cancerous process.

| S-EPMC5029857 | biostudies-other

Mouse Striatum 18 months of age

Project description:The striatum is a functionally diverse brain region. We investigated aged astrocyte and glia diversity within this brain region.

2024-10-03 | GSE226138 | GEO

Prospective Evaluation of Patients With X-Linked Retinoschisis During 18 Months.

Project description:Purpose:Prospective evaluation of patients with X-linked retinoschisis (XLRS). Methods:Fifty-six males XLRS patients, age ≥7 years, had retinal structure and function tests performed every 6 months during an 18-month period. Results:Best corrected visual acuity (BCVA) was abnormal (mean ± SD logMAR 0.57 ± 0.32 OD and 0.50 ± 0.27 OS), with weak correlation between visual acuity and age (R = -0.24, P = 0.0095). Mean cyst cavity volume (CCV) determined on optical coherence tomography showed weak correlation with age (R = -0.33, P = 0.0009) and no correlation with visual acuity. Subjects had modest reduction in mean kinetic and static perimetry results, reduced b-wave amplitude on electroretinography, abnormal reading speed results, and decreased visual function quality of life scores. Contrast sensitivity results were normal in 85 of 99 eyes tested. Most subjects had no meaningful change in BCVA during follow-up. Subjects who started carbonic anhydrase inhibitor (CAI) treatment at enrollment had improved BCVA (mean ± SD change 3.15 ± 7.8 ETDRS letters, with increase of ≥15 ETDRS letters at 8 of 110 visits [in 3 subjects]). There were no significant changes in other parameters tested. Conclusions:Structural and functional results were stable during the 18-month follow-up period. Some patients starting CAI treatment at the baseline visit showed improvement in BCVA that was not correlated with changes in CCV. Natural history data such as these will be important for comparisons to the changes in measures of retinal structure and function following gene replacement therapy in patients with XLRS.

| S-EPMC6295939 | biostudies-literature

Enhanced Neonatal Brain Responses To Sung Streams Predict Vocabulary Outcomes By Age 18 Months.

Project description:Words and melodies are some of the basic elements infants are able to extract early in life from the auditory input. Whether melodic cues contained in songs can facilitate word-form extraction immediately after birth remained unexplored. Here, we provided converging neural and computational evidence of the early benefit of melodies for language acquisition. Twenty-eight neonates were tested on their ability to extract word-forms from continuous flows of sung and spoken syllabic sequences. We found different brain dynamics for sung and spoken streams and observed successful detection of word-form violations in the sung condition only. Furthermore, neonatal brain responses for sung streams predicted expressive vocabulary at 18 months as demonstrated by multiple regression and cross-validation analyses. These findings suggest that early neural individual differences in prosodic speech processing might be a good indicator of later language outcomes and could be considered as a relevant factor in the development of infants' language skills.

| S-EPMC5622081 | biostudies-literature

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