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Pharmacological Research Sep 2021Glioblastoma multiforme (GBM) is a WHO grade IV glioma and the most common malignant, primary brain tumor with a 5-year survival of 7.2%. Its highly infiltrative nature,...
Glioblastoma multiforme (GBM) is a WHO grade IV glioma and the most common malignant, primary brain tumor with a 5-year survival of 7.2%. Its highly infiltrative nature, genetic heterogeneity, and protection by the blood brain barrier (BBB) have posed great treatment challenges. The standard treatment for GBMs is surgical resection followed by chemoradiotherapy. The robust DNA repair and self-renewing capabilities of glioblastoma cells and glioma initiating cells (GICs), respectively, promote resistance against all current treatment modalities. Thus, durable GBM management will require the invention of innovative treatment strategies. In this review, we will describe biological and molecular targets for GBM therapy, the current status of pharmacologic therapy, prominent mechanisms of resistance, and new treatment approaches. To date, medical imaging is primarily used to determine the location, size and macroscopic morphology of GBM before, during, and after therapy. In the future, molecular and cellular imaging approaches will more dynamically monitor the expression of molecular targets and/or immune responses in the tumor, thereby enabling more immediate adaptation of tumor-tailored, targeted therapies.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Drug Resistance, Neoplasm; Glioblastoma; Humans
PubMed: 34302977
DOI: 10.1016/j.phrs.2021.105780 -
Aging Cell Jul 2023Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health-related outcomes, while the causality of these associations remains... (Meta-Analysis)
Meta-Analysis Review
Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health-related outcomes, while the causality of these associations remains unclear. We performed a systematic review and meta-analysis of current evidence from Mendelian randomization (MR) studies on the association between LTL and health-related outcomes. We searched PubMed, Embase, and Web of Science up to April 2022 to identify eligible MR studies. We graded the evidence level of each MR association based on the results of the main analysis and four sensitive MR methods, MR-Egger, weighted median, MR-PRESSO, and multivariate MR. Meta-analyses of published MR studies were also performed. A total of 62 studies with 310 outcomes and 396 MR associations were included. Robust evidence level was observed for the association between longer LTL and increased risk of 24 neoplasms (the strongest magnitude for osteosarcoma, GBM, glioma, thyroid cancer, and non-GBM glioma), six genitourinary and digestive system outcomes of excessive or abnormal growth, hypertension, metabolic syndrome, multiple sclerosis, and clonal hematopoiesis of indeterminate potential. Robust inverse association was observed for coronary heart disease, chronic kidney disease, rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic pulmonary fibrosis, and facial aging. Meta-analyses of MR studies suggested that genetically determined LTL was associated with 12 neoplasms and 9 nonneoplasm outcomes. Evidence from published MR studies supports that LTL plays a causal role in various neoplastic and nonneoplastic diseases. Further research is required to elucidate the underlying mechanisms and to bring insight into the potential prediction, prevention, and therapeutic applications of telomere length.
Topics: Humans; Mendelian Randomization Analysis; Arthritis, Rheumatoid; Glioma; Hypertension; Telomere; Genome-Wide Association Study; Polymorphism, Single Nucleotide
PubMed: 37232505
DOI: 10.1111/acel.13874 -
Seminars in Cancer Biology May 2022The oleogum resins of Boswellia species known as frankincense have been used for ages in traditional medicine in India, China and the Arabian world independent of its... (Review)
Review
The oleogum resins of Boswellia species known as frankincense have been used for ages in traditional medicine in India, China and the Arabian world independent of its use for cultural and religious rituals in Europe. During the past two decades, scientific investigations provided mounting evidence for the therapeutic potential of frankincense. We conducted a systematic review on the anti-inflammatory and anti-cancer activities of Boswellia species and their chemical ingredients (e.g. 3-O-acetyl-11-keto-β boswellic acid, α- and β-boswellic acids, 11-keto-β-boswellic acid and other boswellic acids, lupeolic acids, incensole, cembrenes, triterpenediol, tirucallic acids, and olibanumols). Frankincense acts by multiple mechanisms, e.g. by the inhibition of leukotriene synthesis, of cyclooxygenase 1/2 and 5-lipoxygenase, of oxidative stress, and by regulation of immune cells from the innate and acquired immune systems. Furthermore, frankincense modulates signaling transduction responsible for cell cycle arrest and inhibition of proliferation, angiogenesis, invasion and metastasis. Clinical trials showed the efficacy of frankincense and its phytochemicals against osteoarthritis, multiple sclerosis, asthma, psoriasis and erythematous eczema, plaque-induced gingivitis and pain. Frankincense revealed beneficial effects towards brain tumor-related edema, but did not reduce glioma size. Even if there is no treatment effect on brain tumors itself, the management of glioma-associated edema may represent a desirable improvement. The therapeutic potential against other tumor types is still speculative. Experimental toxicology and clinical trials revealed only mild adverse side effects. More randomized clinical trials are required to estimate the full clinical potential of frankincense for cancer therapy.
Topics: Anti-Inflammatory Agents; Boswellia; Frankincense; Glioma; Humans; Immunologic Factors; Resins, Plant
PubMed: 32027979
DOI: 10.1016/j.semcancer.2020.01.015 -
European Radiology Nov 2022(1) To evaluate the diagnostic performance of radiomics in differentiating high-grade glioma from brain metastasis and how to improve the model. (2) To assess the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
(1) To evaluate the diagnostic performance of radiomics in differentiating high-grade glioma from brain metastasis and how to improve the model. (2) To assess the methodological quality of radiomics studies and explore ways of embracing the clinical application of radiomics.
METHODS
Studies using radiomics to differentiate high-grade glioma from brain metastasis published by 26 July 2021 were systematically reviewed. Methodological quality and risk of bias were assessed using the Radiomics Quality Score (RQS) system and Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool, respectively. Pooled sensitivity and specificity of the radiomics model were also calculated.
RESULTS
Seventeen studies combining 1,717 patients were included in the systematic review, of which 10 studies without data leakage suspicion were employed for the quantitative statistical analysis. The average RQS was 5.13 (14.25% of total), with substantial or almost perfect inter-rater agreements. The inclusion of clinical features in the radiomics model was only reported in one study, as was the case for publicly available algorithm code. The pooled sensitivity and specificity were 84% (95% CI, 80-88%) and 84% (95% CI, 81-87%), respectively. The performances of feature extraction from the volume of interest (VOI) or (semi) automatic segmentation in the radiomics models were superior to those of protocols employing region of interest (ROI) or manual segmentation.
CONCLUSION
Radiomics can accurately differentiate high-grade glioma from brain metastasis. The adoption of standardized workflow to avoid potential data leakage as well as the integration of clinical features and radiomics are advised to consider in future studies.
KEY POINTS
• The pooled sensitivity and specificity of radiomics for differentiating high-grade gliomas from brain metastasis were 84% and 84%, respectively. • Avoiding potential data leakage by adopting an intensive and standardized workflow is essential to improve the quality and generalizability of the radiomics model. • The application of radiomics in combination with clinical features in differentiating high-grade gliomas from brain metastasis needs further validation.
Topics: Humans; Magnetic Resonance Imaging; Glioma; Brain Neoplasms; Sensitivity and Specificity
PubMed: 35587827
DOI: 10.1007/s00330-022-08828-x -
International Journal of Molecular... Oct 2023Glioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients... (Review)
Review
Glioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients remains poor. Immunotherapy has recently emerged as a potential treatment option. The aim of this systematic review is to assess the current strategies and future perspectives of the GBM immunotherapy strategies. A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 3 September 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "glioblastomas," "immunotherapies," and "treatment." The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of immunotherapies for the treatment of gliomas in human subjects. A total of 1588 papers are initially identified. Eligibility is confirmed for 752 articles, while 655 are excluded for various reasons, including irrelevance to the research topic (627), insufficient method and results details (12), and being case-series or cohort studies (22), systematic literature reviews, or meta-analyses (3). All the studies within the systematic review were clinical trials spanning from 1995 to 2023, involving 6383 patients. Neuro-oncology published the most glioma immunotherapy-related clinical trials (15/97, 16%). Most studies were released between 2018 and 2022, averaging nine publications annually during this period. Adoptive cellular transfer chimeric antigen receptor (CAR) T cells were the primary focus in 11% of the studies, with immune checkpoint inhibitors (ICIs), oncolytic viruses (OVs), and cancer vaccines (CVs) comprising 26%, 12%, and 51%, respectively. Phase-I trials constituted the majority at 51%, while phase-III trials were only 7% of the total. Among these trials, 60% were single arm, 39% double arm, and one multi-arm. Immunotherapies were predominantly employed for recurrent GBM (55%). The review also revealed ongoing clinical trials, including 9 on ICIs, 7 on CVs, 10 on OVs, and 8 on CAR T cells, totaling 34 trials, with phase-I trials representing the majority at 53%, and only one in phase III. Overcoming immunotolerance, stimulating robust tumor antigen responses, and countering immunosuppressive microenvironment mechanisms are critical for curative GBM immunotherapy. Immune checkpoint inhibitors, such as PD-1 and CTLA-4 inhibitors, show promise, with the ongoing research aiming to enhance their effectiveness. Personalized cancer vaccines, especially targeting neoantigens, offer substantial potential. Oncolytic viruses exhibited dual mechanisms and a breakthrough status in the clinical trials. CAR T-cell therapy, engineered for specific antigen targeting, yields encouraging results, particularly against IL13 Rα2 and EGFRvIII. The development of second-generation CAR T cells with improved specificity exemplifies their adaptability.
Topics: Humans; Glioblastoma; Immune Checkpoint Inhibitors; Cancer Vaccines; Neoplasm Recurrence, Local; Glioma; Immunotherapy; Immunotherapy, Adoptive; Brain Neoplasms; Tumor Microenvironment
PubMed: 37894718
DOI: 10.3390/ijms242015037 -
Journal of Clinical Oncology : Official... Feb 2022To provide guidance to clinicians regarding therapy for diffuse astrocytic and oligodendroglial tumors in adults.
PURPOSE
To provide guidance to clinicians regarding therapy for diffuse astrocytic and oligodendroglial tumors in adults.
METHODS
ASCO and the Society for Neuro-Oncology convened an Expert Panel and conducted a systematic review of the literature.
RESULTS
Fifty-nine randomized trials focusing on therapeutic management were identified.
RECOMMENDATIONS
Adults with newly diagnosed oligodendroglioma, isocitrate dehydrogenase (IDH)-mutant, 1p19q codeleted CNS WHO grade 2 and 3 should be offered radiation therapy (RT) and procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ) is a reasonable alternative for patients who may not tolerate PCV, but no high-level evidence supports upfront TMZ in this setting. People with newly diagnosed astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 2 should be offered RT with adjuvant chemotherapy (TMZ or PCV). People with astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 should be offered RT and adjuvant TMZ. People with astrocytoma, IDH-mutant, CNS WHO grade 4 may follow recommendations for either astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 or glioblastoma, IDH-wildtype, CNS WHO grade 4. Concurrent TMZ and RT should be offered to patients with newly diagnosed glioblastoma, IDH-wildtype, CNS WHO grade 4 followed by 6 months of adjuvant TMZ. Alternating electric field therapy, approved by the US Food and Drug Administration, should be considered for these patients. Bevacizumab is not recommended. In situations in which the benefits of 6-week RT plus TMZ may not outweigh the harms, hypofractionated RT plus TMZ is reasonable. In patients age ≥ 60 to ≥ 70 years, with poor performance status or for whom toxicity or prognosis are concerns, best supportive care alone, RT alone (for promoter unmethylated tumors), or TMZ alone (for promoter methylated tumors) are reasonable treatment options. Additional information is available at www.asco.org/neurooncology-guidelines.
Topics: Astrocytoma; Brain Neoplasms; Clinical Decision-Making; Consensus; Evidence-Based Medicine; Humans; Medical Oncology; Oligodendroglioma; Predictive Value of Tests; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 34898238
DOI: 10.1200/JCO.21.02036 -
Cancers Aug 2023Over the last 20 years, gliomas have made up over 89% of malignant CNS tumor cases in the American population (NIH SEER). Within this, glioblastoma is the most common... (Review)
Review
Over the last 20 years, gliomas have made up over 89% of malignant CNS tumor cases in the American population (NIH SEER). Within this, glioblastoma is the most common subtype, comprising 57% of all glioma cases. Being highly aggressive, this deadly disease is known for its high genetic and phenotypic heterogeneity, rendering a complicated disease course. The current standard of care consists of maximally safe tumor resection concurrent with chemoradiotherapy. However, despite advances in technology and therapeutic modalities, rates of disease recurrence are still high and survivability remains low. Given the delicate nature of the tumor location, remaining margins following resection often initiate disease recurrence. Photodynamic therapy (PDT) is a therapeutic modality that, following the administration of a non-toxic photosensitizer, induces tumor-specific anti-cancer effects after localized, wavelength-specific illumination. Its effect against malignant glioma has been studied extensively over the last 30 years, in pre-clinical and clinical trials. Here, we provide a comprehensive review of the three generations of photosensitizers alongside their mechanisms of action, limitations, and future directions.
PubMed: 37568734
DOI: 10.3390/cancers15153918 -
Turkish Neurosurgery 2017Malignant glioma is the most common primary brain tumor in adults and the survival rate has remained very low. Thus, determining the optimal treatment for patients can... (Meta-Analysis)
Meta-Analysis Review
AIM
Malignant glioma is the most common primary brain tumor in adults and the survival rate has remained very low. Thus, determining the optimal treatment for patients can be challenging. To compare the efficacy of common therapies, we performed network meta-analysis to estimate the efficacy and safety among procarbazine, lomustine, vincristine, temozolomide, bevacizumab plus temozolomide, and placebo for patients with malignant glioma.
MATERIAL AND METHODS
Relevant studies (as of March, 2014) were identified by searching PubMed, Embase, and Central databases. The primary endpoint of the analysis was the overall survival (OS) and progression-free survival (PFS) of glioma patients.
RESULTS
Nine trials with a total of 3472 patients were included in our network meta-analyses. Compared with placebo, bevacizumab plus temozolomide was associated with the highest estimates of OS and PFS for 12 and 24 months (12 month OS odds ratio [OR]: 2.44; 95% credibility interval [CrIs]: 0.76-9.69; 24 month OS OR: 2.56; 95% CrIs: 1.12?5.24; 12 month PFS OR: 6.76; 95% CrIs: 2.80?17.34; 24 month PFS OR: 3.69; 95% CrIs: 0.62?28.63). However, bevacizumab plus temozolomide did not significantly improve OS or PFS compared to temozolomide alone.
CONCLUSION
Bevacizumab plus temozolomide combination therapy is not significantly more effective than temozolomide alone in improving survival of glioma patients. Moreover, bevacizumab was associated with higher hematologic toxicities. Bevacizumab should be used with caution in glioma patients. Additional randomized controlled trials are required to confirm this finding.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Disease-Free Survival; Glioma; Humans; Network Meta-Analysis
PubMed: 27337236
DOI: 10.5137/1019-5149.JTN.15462-15.0 -
Arkhiv Patologii 2018Gemistocytic astrocytomas (GA) are a variant of diffuse astrocytomas GII (WHO, 2016). Like all diffuse astrocytomas, GA recur with time, which is often accompanied by...
Gemistocytic astrocytomas (GA) are a variant of diffuse astrocytomas GII (WHO, 2016). Like all diffuse astrocytomas, GA recur with time, which is often accompanied by malignant degeneretion into the anaplastic astrocytoma GIII or to the secondary glioblastoma GIV. However, the progression-free survival and overall survival in patients with GA is less than in patients with diffuse astrocytomas. Given that this group of patients, according to the WHO classification (2016), is classified as GII, patients with GA usually do not receive comprehensive treatment. We have conducted a thorough analysis of research on this problem for the period from 1956 to 2017. Differences in the histological pattern, immunohistochemical and molecular-genetic profiles, survival of patients with GA and diffuse astrocytomas GII are shown there. A clinical case of a patient with transformation of a diffuse astrocytoma in GA (GIII) and then into a secondary glioblastoma is presented.
Topics: Adult; Astrocytoma; Brain Neoplasms; ErbB Receptors; Gene Expression Regulation, Neoplastic; Humans; Male; Mutation; Neoplasm Proteins
PubMed: 30059069
DOI: 10.17116/patol201880427 -
PloS One 2017Many studies have previously investigated the potential association between mobile phone use and the risk of glioma. However, results from these individual studies are... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Many studies have previously investigated the potential association between mobile phone use and the risk of glioma. However, results from these individual studies are inconclusive and controversial. The objective of our study was to investigate the potential association between mobile phone use and subsequent glioma risk using meta-analysis.
METHODS
We performed a systematic search of the Science Citation Index Embase and PubMed databases for studies reporting relevant data on mobile phone use and glioma in 1980-2016. The data were extracted and measured in terms of the odds ratio (OR) and 95% confidence interval (CI) using the random effects model. Subgroup analyses were also carried out. This meta-analysis eventually included 11 studies comprising a total 6028 cases and 11488 controls.
RESULTS
There was a significant positive association between long-term mobile phone use (minimum, 10 years) and glioma (OR = 1.44, 95% CI = 1.08-1.91). And there was a significant positive association between long-term ipsilateral mobile phone use and the risk of glioma (OR = 1.46, 95% CI = 1.12-1.92). Long-term mobile phone use was associated with 2.22 times greater odds of low-grade glioma occurrence (OR = 2.22, 95% CI = 1.69-2.92). Mobile phone use of any duration was not associated with the odds of high-grade glioma (OR = 0.81, 95% CI = 0.72-0.92). Contralateral mobile phone use was not associated with glioma regardless of the duration of use. Similarly, this association was not observed when the analysis was limited to high-grade glioma.
CONCLUSIONS
Our results suggest that long-term mobile phone use may be associated with an increased risk of glioma. There was also an association between mobile phone use and low-grade glioma in the regular use or long-term use subgroups. However, current evidence is of poor quality and limited quantity. It is therefore necessary to conduct large sample, high quality research or better characterization of any potential association between long-term ipsilateral mobile phone use and glioma risk.
Topics: Brain Neoplasms; Cell Phone; Glioma; Humans; Risk Factors
PubMed: 28472042
DOI: 10.1371/journal.pone.0175136