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Clinical & Translational Oncology :... Feb 2024Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges in GBM therapeutics have shed light on zebrafish used as a promising animal... (Review)
Review
Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges in GBM therapeutics have shed light on zebrafish used as a promising animal model for preclinical GBM xenograft studies without a standardized methodology. This systematic review aims to summarize the advances in zebrafish GBM xenografting, compare research protocols to pinpoint advantages and underlying limitations, and designate the predominant xenografting parameters. Based on the PRISMA checklist, we systematically searched PubMed, Scopus, and ZFIN using the keywords "glioblastoma," "xenotransplantation," and "zebrafish" for papers published from 2005 to 2022, available in English. 46 articles meeting the review criteria were examined for the zebrafish strain, cancer cell line, cell labeling technique, injected cell number, time and site of injection, and maintenance temperature. Our review designated that AB wild-type zebrafish, Casper transparent mutants, transgenic Tg(fli1:EGFP), or crossbreeding of these predominate among the zebrafish strains. Orthotopic transplantation is more commonly employed. A number of 50-100 cells injected at 48 h post-fertilization in high density and low infusion volume is considered as an effective xenografting approach. U87 cells are used for GBM angiogenesis studies, U251 for GBM proliferation studies, and patient-derived xenograft (PDX) to achieve clinical relevance. Gradual acclimatization to 32-33 °C can partly address the temperature differential between the zebrafish and the GBM cells. Zebrafish xenograft models constitute valuable tools for preclinical studies with clinical relevance regarding PDX. The GBM xenografting research requires modification based on the objective of each research team. Automation and further optimization of the protocol parameters could scale up the anticancer drug trials.
Topics: Animals; Humans; Glioblastoma; Transplantation, Heterologous; Zebrafish; Heterografts; Brain Neoplasms; Cell Line, Tumor; Xenograft Model Antitumor Assays; Disease Models, Animal
PubMed: 37400666
DOI: 10.1007/s12094-023-03258-7 -
Journal of Neuro-oncology Dec 2021Thalamic gliomas are rare neoplasms that pose significant surgical challenges. The literature is limited to single-institution retrospective case series. We... (Review)
Review
PURPOSE
Thalamic gliomas are rare neoplasms that pose significant surgical challenges. The literature is limited to single-institution retrospective case series. We systematically review the literature and describe the clinical characteristics, treatment strategies, and survival outcomes of adult thalamic gliomas.
METHODS
Relevant articles were identified on PubMed, Scopus, and Cochrane databases. Papers containing cases of adult thalamic gliomas with clinical outcome data were included. A comprehensive review of clinical characteristics and survival analysis was conducted.
RESULTS
We included 25 studies comprising 617 patients. The median age was 45 years (male = 58.6%). Glioblastoma was the most frequent histological type (47.2%), and 82 tumors were H3 K27M-mutant. Motor deficit was the most common presenting symptom (51.8%). Surgical resection was performed in 69.1% of cases while adjuvant chemotherapy and radiotherapy were administered in 56.3% and 72.6%, respectively. Other treatments included laser interstitial thermal therapy, which was performed in 15 patients (2.4%). The lesion laterality (P = 0.754) and the surgical approach (P = 0.111) did not correlate with overall survival. The median progression-free survival was 9 months, and the overall two-year survival rate was 19.7%. The two-year survival rates of low-grade and high-grade thalamic gliomas were 31.0% and 16.5%, respectively. H3 K27M-mutant gliomas showed worse overall survival (P = 0.017).
CONCLUSION
Adult thalamic gliomas are associated with poor survival. Complete surgical resection is associated with improved survival rates but is not always feasible. H3 K27M mutation is associated with worse survival and a more aggressive approach should be considered for mutant neoplasms.
Topics: Brain Neoplasms; Glioma; Histones; Humans; Middle Aged; Mutation; Retrospective Studies
PubMed: 34797525
DOI: 10.1007/s11060-021-03898-1 -
Leukemia & Lymphoma Sep 2023Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) chacaterized by persistent peripheral blood monocytosis,...
Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) chacaterized by persistent peripheral blood monocytosis, hypercellular bone marrow and dysplasia at least in one myeloid lineage. CMML shares much of its molecular landscape with other myeloid neoplasms, while differs from others such as chronic neutrophilic leukemia (CNL), given the high frequency of CSF3R mutations in the latter. In this article, we report a case of CSF3R-mutated CMML and dissect this rare entity by reviewing the medical literature, with the intent to understand how this rare mutation shapes CMML's clinical and morphological phenotype. CSF3R-mutated CMML emerges as a rare entity meeting the ICC/WHO diagnostic criteria for CMML and simultaneously showing clinical-pathological and molecular traits of CNL and atypical chronic myeloid leukemia, rising an important and difficult diagnostic and therapeutical issue.
Topics: Humans; Leukemia, Myelomonocytic, Chronic; Leukemia, Neutrophilic, Chronic; Mutation; Myeloproliferative Disorders; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Prognosis; Receptors, Colony-Stimulating Factor
PubMed: 37395413
DOI: 10.1080/10428194.2023.2227750 -
Current Issues in Molecular Biology Oct 2022Both (isocitrate dehydrogenase 1) and (isocitrate dehydrogenase 2) mutations play a vital role in the development of gliomas through disruption of normal cellular...
Both (isocitrate dehydrogenase 1) and (isocitrate dehydrogenase 2) mutations play a vital role in the development of gliomas through disruption of normal cellular metabolic processes. Here we describe a case of a patient with an IDH-mutant astrocytoma, in which both and mutations were detected within the same tumour. The patient remains disease-free, nine and a half years after her initial diagnosis. Interrogation of cancer genomic databases and a systematic review was undertaken, demonstrating the rarity of the co-occurrence of and mutations in a variety of cancer types, and in glioma specifically. Due to the favourable outcome observed in this patient, the potential effect of concurrent and mutations on survival was also investigated.
PubMed: 36286062
DOI: 10.3390/cimb44100348 -
Diagnostics (Basel, Switzerland) Sep 2021The study's objective was the evaluation of the diagnostic accuracy of the T2-FLAIR mismatch sign in terms of diagnosing IDH-mutant non-codeleted (IDHmut-Noncodel) lower... (Review)
Review
The study's objective was the evaluation of the diagnostic accuracy of the T2-FLAIR mismatch sign in terms of diagnosing IDH-mutant non-codeleted (IDHmut-Noncodel) lower grade gliomas (LGG) of the brain. We searched the MEDLINE, Scopus and Cochrane Central databases. The last database search was performed on 12 April 2021. Studies that met the following were included: MRI scan assessing the presence of T2-FLAIR mismatch sign, and available IDH mutation and 1p/19q codeletion status. The quality of studies was assessed using the QUADAS-2 tool. Twelve studies involving 14 cohorts were included in the quantitative analysis. The diagnostic odds ratio [DOR (95% confidence interval; CI)] was estimated at 34.42 (20.95, 56.56), < 0.01. Pooled sensitivity and specificity (95% CI) were estimated at 40% (31-50%; = 0.05) and 97% (93-99%; < 0.01), respectively. The likelihood ratio (LR; 95% CI) for a positive test was 11.39 (6.10, 21.29; < 0.01) and the LR (95% CI) for a negative test was 0.40 (0.24, 0.65; < 0.01).The T2-FLAIR mismatch sign is a highly specific biomarker for the diagnosis of IDHmut-Noncodel LGGs. However, the test was found positive in some other tumors and had a high number of false negative results. The diagnostic accuracy of the mismatch sign might be improved when combined with further imaging parameters.
PubMed: 34573962
DOI: 10.3390/diagnostics11091620 -
Current Pharmaceutical Biotechnology 2023Periodontal diseases and dental caries are the two most common dental diseases caused by the dental plaque.
INTRODUCTION
Periodontal diseases and dental caries are the two most common dental diseases caused by the dental plaque.
OBJECTIVE
The aim of the present study was to review the clinical efficacy of probiotics for oral health in randomized controlled trials.
METHODS
An electronic search was conducted in December 2021 in Embase, Medline, The Cochrane Library, ProQuest, and Google Scholar using the following keywords: "mouthwash" and "probiotics". The titles and abstracts of 3,775 articles were screened and 24 publications that fulfilled the inclusion criteria were included.
RESULTS
A total of 24 clinical trials were reviewed, including 1612 participants receiving either probiotics or mouth treatments. The results of this review indicated that individuals receiving probiotic products have a significant reduction (65% reduction; < 0.05) in the count of in their mouths. It was also found that probiotic products were more effective or equal in effect compared to chlorhexidine in reducing oral pathogens, gingival index, and plaque index scores. On the other hand, the consumption of xylitol mouthwash was shown to cause an improvement in salivary parameters. Considering their safety and effectiveness, the use of probiotic products, such as kefir and mouthwashes, has been recommended against cariogenic bacteria and periodontal diseases.
CONCLUSION
Probiotics are considered a safe alternative to conventional therapies, such as chlorhexidine and fluoride. Co-administration of chlorhexidine, fluoride, and probiotics seems to be a perfect package.
Topics: Humans; Chlorhexidine; Oral Health; Fluorides; Dental Caries; Mouthwashes; Probiotics; Periodontal Diseases; Treatment Outcome
PubMed: 37038663
DOI: 10.2174/1389201024666230405135457 -
American Journal of Medical Genetics.... Feb 2022Variants in the pleckstrin homology domain-interacting protein (PHIP) gene are implicated in the clinical phenotype of Chung-Jansen syndrome, which includes dysmorphic...
Variants in the pleckstrin homology domain-interacting protein (PHIP) gene are implicated in the clinical phenotype of Chung-Jansen syndrome, which includes dysmorphic features, cognitive dysfunction, aberrant behavior, and childhood onset obesity. Following a systematic literature review, 35 patients are reported to have unique PHIP variants impacting the encoded protein product. We summarize the status and frequency of these variants and relationship to clinical presentation. We also describe an additional patient with a rare, pathogenic variant due to a five base pair deletion leading to an altered codon at I307 but with a stop codon at 22 codons downstream; notably, a variant was identified at the same location as seen previously at protein position I307 in one other subject and a frameshift change at that protein position. We compare the clinical characteristics between the two patients and analyze whether certain types of gene defects impact clinical presentation in previously reported individuals. In addition, we predict structural protein models, which yielded unique differences between the wild-type and I307P-related mutant truncated proteins. Protein-protein interactions indicate involvement of POMC and related proteins with potential contribution to obesity, congenital, neuromuscular, and lipid disorders with heart, gastrointestinal, and rheumatoid diseases. With its surrounding proline-rich region, the I307P point mutation increases susceptibility to conformational rigidity and thermodynamic stability, ultimately impacting function as well as a stop codon downstream. Furthermore, the frameshift mutation seen in our patient may result in a truncated protein with a short abnormal region prior to the stop codon due to a five base pair deletion at I307 or target the protein for nonsense-mediated mRNA decay.
Topics: Child; Frameshift Mutation; Humans; Nonsense Mediated mRNA Decay; Phenotype
PubMed: 34773373
DOI: 10.1002/ajmg.a.62557 -
Frontiers in Oncology 2022Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in non-small cell lung cancer (NSCLC). However, only a minority of NSCLC patients benefit from...
BACKGROUND
Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in non-small cell lung cancer (NSCLC). However, only a minority of NSCLC patients benefit from ICIs, and whether the magnitude of benefit is specific factor-dependent remains unclear. We performed a systematic review to improve our understanding of clinicopathologic and biomolecular features associated with improved survival upon treatment with ICIs for NSCLC.
METHODS
We searched PubMed, Web of Science, Embase, and Scopus from database inception to August 31, 2021, for randomized controlled trials (RCTs) comparing overall survival (OS) in NSCLC treated with ICIs vs control therapies. We calculated the pooled OS hazard ratio (HR) and 95% CI in subgroups using a random-effects model, and assessed the heterogeneity between the paired estimates using an interaction test.
RESULTS
A total of 23 RCTs involving 15,829 patients were included. We found that wild-type EGFR, high PD-L1 expression, and high bTMB were associated with a significant OS benefit from ICIs, but not mutant EGFR, low PD-L1 expression, and low bTMB. The differences of OS benefit between wild-type and mutant EGFR (HR=1.53, 95%CI 1.13-2.08), high and low PD-L1 (HR=1.35; 95%CI 1.14-1.61), high and low bTMB (HR=1.71; 95%CI 1.17-2.52) were statistically significant. OS benefit was found in all subgroups regardless of sex, age, ECOG PS, histology, smoking history, baseline brain metastasis, race, and region, and the interaction test demonstrated no significant difference of the OS benefit between these opposed subgroups (e.g. male vs female).
CONCLUSIONS
Wild-type EGFR, high PD-L1 expression, and high bTMB are associated with a greater magnitude of efficacy from ICIs vs control therapies in NSCLC. However, the administration of ICIs should not be restricted to other clinicopathological factors (sex, smoking history, race, etc.).
PubMed: 36052255
DOI: 10.3389/fonc.2022.955440 -
European Radiology Jul 2021To evaluate the diagnostic performance of the T2-FLAIR mismatch sign for prediction of isocitrate dehydrogenase (IDH)-mutant, 1p/19q-noncodeleted lower-grade gliomas... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To evaluate the diagnostic performance of the T2-FLAIR mismatch sign for prediction of isocitrate dehydrogenase (IDH)-mutant, 1p/19q-noncodeleted lower-grade gliomas (LGGs) and review studies with false positive results.
METHODS
The MEDLINE and EMBASE databases were searched up to March 13, 2020, to identify articles reporting the diagnostic performance of the T2-FLAIR mismatch sign for prediction of IDH-mutant, 1p/19q-noncodeleted LGGs (IDHmut-Noncodel) using the search terms (T2 FLAIR mismatch). Pooled sensitivity, specificity, and correlation coefficient for interobserver agreement were calculated.
RESULTS
Twelve studies including a total of 1053 patients were included. The median age was 43 (median; range, 14-56). The pooled sensitivity and specificity were 42% (95% CI, 28-58%) and 100% (95% CI, 88-100%), respectively. According to the HSROC curve, the area under the curve was 0.77 (95% CI, 0.73-0.80). Considerable heterogeneity was possible among the studies in terms of both sensitivity and specificity. A threshold effect was suggested and was considered to explain most of the heterogeneity. Four studies reported false positive results for the T2-FLAIR mismatch sign, including dysembryoplastic neuroepithelial tumor, pediatric-type gliomas, and non-neoplastic lesions. The 2 original articles with false positive results showed the highest sensitivities among the 10 studies included in the quantitative analysis, supporting the probability of the threshold effect. The pooled correlation coefficient was 0.87 (95% CI, 0.73-0.94).
CONCLUSIONS
The T2-FLAIR mismatch sign had a high specificity and interobserver agreement for the prediction of IDHmut-Noncodel. However, the sign demonstrated low sensitivity, and a few studies with false positive cases were also reported.
KEY POINTS
• The pooled sensitivity and specificity of the T2-FLAIR mismatch sign for prediction of IDH-mutant, 1p/19q-noncodeleted lower-grade gliomas were 42% and 100%, respectively. • Four studies reported false positive results. • The pooled correlation coefficient was 0.87, suggesting almost perfect interobserver agreement.
Topics: Adult; Brain Neoplasms; Child; Glioma; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Mutation; Retrospective Studies
PubMed: 33409784
DOI: 10.1007/s00330-020-07467-4 -
Journal of Tropical Medicine 2023The PRISMA statement was strictly followed, and the protocol was registered in PROSPERO (CRD42022339317). The PICOS framework was used: patients received... (Review)
Review
METHODS
The PRISMA statement was strictly followed, and the protocol was registered in PROSPERO (CRD42022339317). The PICOS framework was used: patients received antituberculosis treatment, UGTs polymorphisms (mutants), UGTs polymorphisms (wild), AT-DILI, and case-control studies. Eligible studies were searched through nine databases up to April 27, 2022. The study's qualities were assessed by the revised Little's recommendations. Meta-analysis was conducted with a random-effects model using odds ratios (ORs) with 95% confidence intervals (95% CIs) as the effect size.
RESULTS
Twelve case-control studies with 2128 cases and 4338 controls were included, and 32 single nucleotide polymorphisms (SNPs) in the seven UGT genes have been reported in Chinese and Korean. All studies were judged as high quality. The pooled results indicated that UGT1A1 rs3755319 (AC vs. AA, OR = 1.454, 95% CI: 1.100-1.921, = 0.009), UGT2B7 rs7662029 (G vs. A, OR = 1.547, 95% CI: 1.249-1.917, < 0.0001; GG + AG vs. AA, OR = 2.371, 95% CI: 1.779-3.160, < 0.0001; AG vs. AA, OR = 2.686, 95% CI: 1.988-3.627, < 0.0001), and UGT2B7 rs7439366 (C vs. T, OR = 0.585, 95% CI: 0.477-0.717, < 0.0001; CC + TC vs. TT, OR = 0.347, 95% CI: 0.238-0.506, < 0.0001; CC vs. TC + TT, OR = 0.675, 95% CI: 0.507-0.898, = 0.007) might be associated with the risk of AT-DILI.
CONCLUSIONS
The polymorphisms of UGT1A1 rs3755319, UGT2B7 rs7662029, and UGT2B7 rs7439366 were significantly associated with AT-DILI susceptibility. However, this conclusion should be interpreted with caution due to the low number of studies and the relatively small sample size.
PubMed: 37868740
DOI: 10.1155/2023/5044451