Elevated plasma 20S proteasome chymotrypsin-like activity is correlated with IL-8 levels and associated with an increased risk of death in glial brain tumor patients

Abstract INTRODUCTION Reduced triiodothyronine (T3) concentrations were implicated in worse prognosis of brain tumor patients. We investigated the association of thyroid hormone concentrations with health-related quality of life (HRQoL), discharge outcomes and prognosis of brain tumor patients. METHODS Two-hundred and thirty brain tumor patients (70% women) before brain tumor surgery were evaluated for HRQoL (ERTC QLQ-C30 and QLQ-BN20 questionnaires); and thyroid function profile. The Low tri-iodothyronine (T3) syndrome was defined as T3 concentration below the reference range. Unfavorable hospital discharge outcomes were determined as Glasgow outcome scale score of = 3. Follow-up continued until November, 2015. RESULTS >Seventy-four percent of patients had Low T3 syndrome. After adjusting for the brain tumor histological diagnosis, patients' age, gender and functional status, lower free T3 concentrations were associated with worse HRQOL on the QLQ-C30 Global health status (ß = 0.302, P = 0.017), Emotional functioning (ß = 0.422, p<.001) and Cognitive functioning (ß = 0.259, P = 0.042) domains, and with greater symptom severity on the QLQ-BN20 Fatigue (ß = −0.238, p = .041), Motor dysfunction (ß = −0.283, P = 0.013) and Weakness of legs (ß = −0.269. P = 0.027) domains. Preoperative Low T3 syndrome increased risk for unfavorable discharge outcomes adjusting for age, gender and histological diagnosis (OR = 2.944, 95%CI [1.314-6.597], p = .009). In all patients, lower total (p = .038) and free (p = .014) T3 concentrations were associated with greater mortality adjusting for age, gender, extent of resection, adjuvant treatment and histological diagnosis. The Low T3 syndrome was associated with greater 5-year mortality for glioma patients (HR = 2.197; 95%CI [1.160-4.163], p = .016) and with shorter survival (249 [260] vs. 352 [399] days; p = .029) of high grade glioma patients independent of age, gender, extent of resection and adjuvant treatment. CONCLUSION The Low T3 syndrome is common in brain tumor patients and is associated with worse health status, impaired emotional and physical aspects of HRQoL and worse discharge outcomes. The Low T3 syndrome is associated with shorter survival of glioma patients.

Download Full-text

Biomarkers and focused ultrasound: the future of liquid biopsy for brain tumor patients

Journal of Neuro-Oncology ◽

10.1007/s11060-021-03837-0 ◽

2021 ◽

Author(s):

Jordina Rincon-Torroella ◽

Harmon Khela ◽

Anya Bettegowda ◽

Chetan Bettegowda

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Liquid Biopsy ◽

Focused Ultrasound ◽

Modern Medicine ◽

Detection Methods ◽

Liquid Biopsies ◽

Tumor Patients ◽

Clinical Trial Registries ◽

Increased Risk

Abstract Introduction Despite advances in modern medicine, brain tumor patients are still monitored purely by clinical evaluation and imaging. Traditionally, invasive strategies such as open or stereotactic biopsies have been used to confirm the etiology of clinical and imaging changes. Liquid biopsies can enable physicians to noninvasively analyze the evolution of a tumor and a patient’s response to specific treatments. However, as a consequence of biology and the current limitations in detection methods, no blood or cerebrospinal fluid (CSF) brain tumor-derived biomarkers are used in routine clinical practice. Enhancing the presence of tumor biomarkers in blood and CSF via brain-blood barrier (BBB) disruption with MRI-guided focused ultrasound (MRgFUS) is a very compelling strategy for future management of brain tumor patients. Methods A literature review on MRgFUS-enabled brain tumor liquid biopsy was performed using Medline/Pubmed databases and clinical trial registries. Results The therapeutic applications of MRgFUS to target brain tumors have been under intense investigation. At high-intensity, MRgFUS can ablate brain tumors and target tissues, which needs to be balanced with the increased risk for damage to surrounding normal structures. At lower-intensity and pulsed-frequency, MRgFUS may be able to disrupt the BBB transiently. Thus, while facilitating intratumoral or parenchymal access to standard or novel therapeutics, BBB disruption with MRgFUS has opened the possibility of enhanced detection of brain tumor-derived biomarkers. Conclusions In this review, we describe the concept of MRgFUS-enabled brain tumor liquid biopsy and present the available preclinical evidence, ongoing clinical trials, limitations, and future directions of this application.

Download Full-text

Polymorphism in miRNA target sites of CEP-63 and CEP-152 ring complex influences expression of CEP genes and favors tumorigenesis in glioma

Future Oncology ◽

10.2217/fon-2020-1034 ◽

2021 ◽

Author(s):

Ishrat Mahjabeen ◽

Yusra Maqsood ◽

Ramsha Abbasi ◽

Malik Waqar Ahmed ◽

Mahmood Akhtar Kayani

Keyword(s):

Brain Tumor ◽

Amplification Refractory Mutation System ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Tumor Patients ◽

Single Nucleotide ◽

Tissue Samples ◽

Mutant Genotype ◽

Normal Tissues ◽

Increased Risk

Purpose: The present study was designed to screen the genetic polymorphisms and expression profiling of CEP-152 and CEP-63 genes in brain tumor patients. Methods: The amplification refractory mutation system PCR technique (ARMS-PCR) was used for mutation analysis using 300 blood samples of brain tumor patients and 300 overtly healthy controls. For expression analysis, 150 brain tumor tissue samples along with adjacent uninvolved/normal tissues (controls) were collected. Results: A significantly higher frequency of the mutant genotype of the CEP-152 single nucleotide polymorphism (rs2169757) and CEP-63 single nucleotide polymorphisms (rs9809619 and rs13060247) was observed in patients versus overtly healthy controls. The authors' results showed highly significant deregulation of CEP-152 (p < 0.0001) and CEP-63 (p < 0.0001) in glioma/meningioma tumor tissues versus adjacent normal tissue. Conclusion: The present study showed that variations in CEP-152 and CEP-63 genes were associated with an increased risk of brain tumor.

Download Full-text

Genetic and expression variations of cell cycle pathway genes in brain tumor patients

Bioscience Reports ◽

10.1042/bsr20190629 ◽

2020 ◽

Vol 40 (5) ◽

Author(s):

Anum Zehra Naqvi ◽

Ishrat Mahjabeen ◽

Saima Ameen ◽

Malik Waqar Ahmed ◽

Asad Ullah Khan ◽

...

Keyword(s):

Brain Tumor ◽

Gene Polymorphism ◽

Immunohistochemical Analysis ◽

Significant Negative Correlation ◽

Down Regulation ◽

Tumor Patients ◽

Ki 67 ◽

Mutant Genotype ◽

Tumor Risk ◽

Increased Risk

Abstract The present study was designed to determine the association between the genetic polymorphisms/expression variations of RB1 and CCND1 genes and brain tumor risk. For this purpose, 250 blood samples of brain tumor patients along with 250 controls (cohort I) and 96 brain tumor tissues (cohort II) with adjacent control section were collected. Mutation analysis of RB1 (rs137853294, rs121913300) and CCND1 (rs614367, rs498136) genes was performed using ARMS-PCR followed by sequencing, and expression analysis was performed using real-time PCR and immunohistochemistry. The results showed homozygous mutant genotype of RB1 gene polymorphism, rs121913300 (P=0.003) and CCND1 gene polymorphism rs614367 (P=0.01) were associated significantly with brain tumor risk. Moreover, significant down-regulation of RB1 (P=0.005) and up-regulation of CCND1 (P=0.0001) gene was observed in brain tumor sections vs controls. Spearman correlation showed significant negative correlation between RB1 vs proliferation marker, Ki-67 (r = −0.291*, P<0.05) in brain tumors. Expression levels of selected genes were also assessed at protein level using immunohistochemical analysis (IHC) and signification down-regulation of RB1 (P=0.0001) and up-regulation of CCND1 (P=0.0001) was observed in brain tumor compared with control sections. In conclusion, it is suggested that polymorphisms/expression variations of RB1 and CCND1 genes may be associated with increased risk of brain tumor.

Download Full-text