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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 -
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 Neuro-oncology Aug 2023Tumor Treating Fields (TTFields) therapy, an electric field-based cancer treatment, became FDA-approved for patients with newly diagnosed glioblastoma (GBM) in 2015... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Tumor Treating Fields (TTFields) therapy, an electric field-based cancer treatment, became FDA-approved for patients with newly diagnosed glioblastoma (GBM) in 2015 based on the randomized controlled EF-14 study. Subsequent approvals worldwide and increased adoption over time have raised the question of whether a consistent survival benefit has been observed in the real-world setting, and whether device usage has played a role.
METHODS
We conducted a literature search to identify clinical studies evaluating overall survival (OS) in TTFields-treated patients. Comparative and single-cohort studies were analyzed. Survival curves were pooled using a distribution-free random-effects method.
RESULTS
Among nine studies, seven (N = 1430 patients) compared the addition of TTFields therapy to standard of care (SOC) chemoradiotherapy versus SOC alone and were included in a pooled analysis for OS. Meta-analysis of comparative studies indicated a significant improvement in OS for patients receiving TTFields and SOC versus SOC alone (HR: 0.63; 95% CI 0.53-0.75; p < 0.001). Among real-world post-approval studies, the pooled median OS was 22.6 months (95% CI 17.6-41.2) for TTFields-treated patients, and 17.4 months (95% CI 14.4-21.6) for those not receiving TTFields. Rates of gross total resection were generally higher in the real-world setting, irrespective of TTFields use. Furthermore, for patients included in studies reporting data on device usage (N = 1015), an average usage rate of ≥ 75% was consistently associated with prolonged survival (p < 0.001).
CONCLUSIONS
Meta-analysis of comparative TTFields studies suggests survival may be improved with the addition of TTFields to SOC for patients with newly diagnosed GBM.
Topics: Humans; Glioblastoma; Temozolomide; Electric Stimulation Therapy; Brain Neoplasms; Combined Modality Therapy
PubMed: 37493865
DOI: 10.1007/s11060-023-04348-w -
Neurosurgical Review Nov 2023Neurosurgical pathologies in pregnancy pose significant complications for the patient and fetus, and physiological stressors during anesthesia and surgery may lead to... (Review)
Review
Neurosurgical pathologies in pregnancy pose significant complications for the patient and fetus, and physiological stressors during anesthesia and surgery may lead to maternal and fetal complications. Awake craniotomy (AC) can preserve neurological functions while reducing exposure to anesthetic medications. We reviewed the literature investigating AC during pregnancy. PubMed, Scopus, and Web of Science databases were searched from the inception to February 7th, 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Studies in English investigating AC in pregnant patients were included in the final analysis. Nine studies composed of nine pregnant patients and ten fetuses (one twin-gestating patient) were included. Glioma was the most common pathology reported in six (66.7%) patients. The frontal lobe was the most involved region (4 cases, 44.4%), followed by the frontoparietal region (2 cases, 22.2%). The awake-awake-awake approach was the most common protocol in seven (77.8%) studies. The shortest operation time was two hours, whereas the longest one was eight hours and 29 min. The mean gestational age at diagnosis was 13.6 ± 6.5 (2-22) and 19.6 ± 6.9 (9-30) weeks at craniotomy. Seven (77.8%) studies employed intraoperative fetal heart rate monitoring. None of the AC procedures was converted to general anesthesia. Ten healthy babies were delivered from patients who underwent AC. In experienced hands, AC for resection of cranial lesions of eloquent areas in pregnant patients is safe and feasible and does not alter the pregnancy outcome.
Topics: Female; Humans; Pregnancy; Brain Neoplasms; Wakefulness; Craniotomy; Glioma; Anesthesia, General
PubMed: 37910275
DOI: 10.1007/s10143-023-02187-x -
Journal of Oncology Pharmacy Practice :... Oct 2023We conducted a systematic review and meta-analysis aiming to assess the efficacy and safety of Nivolumab treatment in patients with newly diagnosed and recurrent... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We conducted a systematic review and meta-analysis aiming to assess the efficacy and safety of Nivolumab treatment in patients with newly diagnosed and recurrent glioblastoma multiforme (GBM).
DATA SOURCES
Our study followed the guidelines outlined in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) recommendations. The protocol for this review can be found in the International Prospective Register of Systematic Reviews Database (CRD42022340071). We performed searches on the Medline, PubMed, Embase, Scopus, and Web of Science databases.
DATA SUMMARY
A total of 545 studies were identified through our comprehensive search across the five databases (PubMed: 78, Embase: 82, Medline: 173, Scopus: 138, Web of Science: 74). After conducting a thorough analysis, our meta-analysis indicated that treatment with Nivolumab led to improved overall survival (OS) outcomes in newly diagnosed glioblastoma patients, as evidenced by a prolonged median OS based on trial data. However, there was no significant beneficial effect observed in terms of median progression-free survival (PFS), as well as OS at 6, 12, and 24 months. Furthermore, our results demonstrated no efficacy of Nivolumab in the treatment of recurrent GBM patients.
CONCLUSIONS
In conclusion, Nivolumab demonstrated promising results that warrant further investigation for its use in newly diagnosed glioblastoma patients. However, its effectiveness was not observed in the context of recurrent GBM.
Topics: Humans; Glioblastoma; Nivolumab; Neoplasm Recurrence, Local; Progression-Free Survival; Brain Neoplasms
PubMed: 37503551
DOI: 10.1177/10781552231190104 -
World Journal of Gastroenterology Feb 2024Most patients with advanced pancreatic neuroendocrine tumors (pNETs) die due to tumor progression. Therefore, identifying new therapies with low toxicity and good... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Most patients with advanced pancreatic neuroendocrine tumors (pNETs) die due to tumor progression. Therefore, identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant. In this perspective, metformin is emerging as a molecule of interest. Retrospective studies have described metformin, a widely used agent for the treatment of patients with type 2 diabetes mellitus (T2DM), to be effective in modulating different tumor-related events, including cancer incidence, recurrence and survival by inhibiting mTOR phosphorylation. This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.
AIM
To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and post-treatment outcomes of pNET.
METHODS
A systematic review of the published literature was undertaken, focusing on the role of T2DM and metformin in insurgence and prognosis of pNET, measured through outcomes of tumor-free survival (TFS), overall survival and progression-free survival.
RESULTS
A total of 13 studies (5674 patients) were included in this review. Analysis of 809 pNET cases from five retrospective studies (low study heterogeneity with = 0%) confirms the correlation between T2DM and insurgence of pNET (OR = 2.13, 95%CI = 1.56-4.55; < 0.001). The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients (hazard ratio = 1.84, 95%CI = 0.78-2.90; < 0.001). The study heterogeneity was intermediate, with = 51%. A few studies limited the possibility of performing pooled analysis in the setting of metformin; therefore, results were heterogeneous, with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.
CONCLUSION
T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients. Unfortunately, a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Neuroendocrine Tumors; Retrospective Studies; Pancreatic Neoplasms; Neuroectodermal Tumors, Primitive
PubMed: 38515954
DOI: 10.3748/wjg.v30.i7.759 -
Biochimica Et Biophysica Acta. Reviews... Jul 2023Glioblastoma multiforme (GBM) is an aggressive brain cancer showing poor prognosis. Currently, treatment methods of GBM are limited with adverse outcomes and low... (Review)
Review
Glioblastoma multiforme (GBM) is an aggressive brain cancer showing poor prognosis. Currently, treatment methods of GBM are limited with adverse outcomes and low survival rate. Thus, advancements in the treatment of GBM are of utmost importance, which can be achieved in recent decades. However, despite aggressive initial treatment, most patients develop recurrent diseases, and the overall survival rate of patients is impossible to achieve. Currently, researchers across the globe target signaling events along with tumor microenvironment (TME) through different drug molecules to inhibit the progression of GBM, but clinically they failed to demonstrate much success. Herein, we discuss the therapeutic targets and signaling cascades along with the role of the organoids model in GBM research. Moreover, we systematically review the traditional and emerging therapeutic strategies in GBM. In addition, we discuss the implications of nanotechnologies, AI, and combinatorial approach to enhance GBM therapeutics.
Topics: Humans; Glioblastoma; Signal Transduction; Tumor Microenvironment
PubMed: 37182666
DOI: 10.1016/j.bbcan.2023.188913 -
Journal of Nanobiotechnology Aug 2023Lymph nodes targeted drug delivery is an attractive approach to improve cancer immunotherapy outcomes. Currently, the depth of understanding of afferent and efferent... (Review)
Review
Lymph nodes targeted drug delivery is an attractive approach to improve cancer immunotherapy outcomes. Currently, the depth of understanding of afferent and efferent arms in brain immunity reveals the potential clinical applications of lymph node targeted drug delivery in brain tumors, e.g., glioblastoma. In this work, we systematically reviewed the microenvironment of glioblastoma and its structure as a basis for potential immunotherapy, including the glial-lymphatic pathway for substance exchange, the lymphatic drainage pathway from meningeal lymphatic vessels to deep cervical lymph nodes that communicate intra- and extracranial immunity, and the interaction between the blood-brain barrier and effector T cells. Furthermore, the carriers designed for lymph nodes targeted drug delivery were comprehensively summarized. The challenges and opportunities in developing a lymph nodes targeted delivery strategy for glioblastoma using nanotechnology are included at the end.
Topics: Humans; Glioblastoma; Lymph Nodes; Brain Neoplasms; Brain; Drug Delivery Systems; Tumor Microenvironment
PubMed: 37542241
DOI: 10.1186/s12951-023-02011-0 -
International Journal of Public Health 2023To study the prevalence and the association of HPV infection in retinoblastoma and to determine the most common genotype presented in RB. Following the PRIMSA... (Meta-Analysis)
Meta-Analysis Review
To study the prevalence and the association of HPV infection in retinoblastoma and to determine the most common genotype presented in RB. Following the PRIMSA guideline, 14 studies reporting HPV infection in RB acquired from six databases were included. The prevalence of HPV from 941 RB samples was 15.6% [95% confidence interval (CI): 7.3-30]. Mexico followed by India and Brazil had the highest HPV prevalence in RB samples, 61.7% (95% CI: 17-93), 22.5% (95% CI: 9-47), and 12.1% (95% CI: 2-52), in order. HPV 16 was the most common genotype presented in RB samples 23% (95% CI: 9-47), followed by HPV 18 10% (95% CI: 3-30) and the combined HPV 16-18 6% (95% CI: 0-50). We did not find a significant association between HPV and RB [odds ratio (OR): 12.2; 95% CI: 0.65-232; = 0.09]. However, after removing the largest-weighted study, a significant association between HPV and RB was observed (OR: 45.9; 95% CI; 8.6-245; < 0.001). HPV prevalence in RB samples was 15% and HPV 16 was the most presented genotype in RB samples. There may be an association between HPV and RB that is needed to be confirmed by high quality future studies. Preventive and treatment measures against HPV infection are essential for the prevention of any possible consequences, in particular, RB.
Topics: Humans; Retinoblastoma; Papillomavirus Infections; Human Papillomavirus Viruses; Cross-Sectional Studies; Human papillomavirus 16; Prevalence; Retinal Neoplasms
PubMed: 37497122
DOI: 10.3389/ijph.2023.1605284 -
Environmental Science and Pollution... Nov 2023While neuroblastoma accounts for an estimated 8% of childhood cancers, it causes about 15% of childhood cancer deaths in the United States. The role of agricultural... (Meta-Analysis)
Meta-Analysis Review
While neuroblastoma accounts for an estimated 8% of childhood cancers, it causes about 15% of childhood cancer deaths in the United States. The role of agricultural exposures in the development of neuroblastoma is unclear. We conducted a systematic review and meta-analysis of studies examining the relationship between agricultural exposures and neuroblastoma. MEDLINE, EMBASE, Scopus, and Google Scholar were searched in February 2022, identifying 742 publications. Seventeen articles met the inclusion criteria; all were published between 1985 and 2020 and included 14 case-control, one cross-sectional, and two cohort studies. Random and fixed effects models were used to calculate summary odds ratios (sORs) and 95% confidence intervals (CIs). An increased odds of developing neuroblastoma with parental exposure to any pesticides (sOR = 1.25, 95% CI: 1.03-1.48; 4 studies), insecticides (sOR = 1.55, 95% CI: 1.19-1.91; 3 studies), and residential exposure to crops/vegetables (sOR = 1.04, 95% CI: 1.01-1.06; 2 studies) was seen. Heterogeneity was low in all analyses, and no publication bias was evident. No significant associations were found with agricultural occupations, herbicides, and agricultural dusts. The studies were limited by exposure measurements and small sample sizes. Further studies are needed to explore mechanisms in the development of neuroblastoma in children with parental agricultural exposures, especially pesticides, and to improve methods of measuring agricultural-related exposures.
Topics: Child; Humans; United States; Cross-Sectional Studies; Agriculture; Pesticides; Dust; Neuroblastoma
PubMed: 37858025
DOI: 10.1007/s11356-023-30315-z