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The British Journal of Oral &... Jun 2024Oral epithelial dysplasia (OED) is a premalignant condition that carries an appreciable risk of malignant progression. The current grading system for severity, as... (Meta-Analysis)
Meta-Analysis Review
Oral epithelial dysplasia (OED) is a premalignant condition that carries an appreciable risk of malignant progression. The current grading system for severity, as defined by the World Health Organization, is a valuable clinical tool, but further work is required to improve the accuracy of predicting OED malignant progression. This systematic review aimed to assess progress in prognostic biomarker discovery in OED over the past 16 years. The primary objective was to update the latest evidence on prognostic biomarkers that may predict malignant progression of OED, with strict inclusion criteria of studies with a longitudinal design and long-term follow-up data to enhance the robustness and translational clinical potential of the findings. Of 2829 studies identified through the searching of five databases, 20 met our inclusion criteria. These studies investigated a total of 32 biomarkers, 20 of which demonstrated significant potential to predict malignant progression of OED. Meta-analysis demonstrated the significant prognostic value of four biomarkers: podoplanin, EGFR expression, p16 methylation, and DNA aneuploidy. Our review has identified 20 reported biomarkers with prognostic potential to predict malignant progression in OED, but their translation into clinical practice remains elusive. Further research is required, and this should focus on validating the promising biomarkers identified in large cohort studies, with adherence to standardised reporting guidelines.
Topics: Humans; Prognosis; Disease Progression; Mouth Neoplasms; Biomarkers, Tumor; Precancerous Conditions; Mouth Mucosa; ErbB Receptors; DNA Methylation; Aneuploidy
PubMed: 38677951
DOI: 10.1016/j.bjoms.2024.03.001 -
Critical Reviews in Oncology/hematology Jun 2024This systematic review summarizes evidence of VEGFR gene mutations and VEGF/VEGFR protein expression in glioblastoma multiforme (GBM) patients, alongside the efficacy... (Review)
Review
PURPOSE
This systematic review summarizes evidence of VEGFR gene mutations and VEGF/VEGFR protein expression in glioblastoma multiforme (GBM) patients, alongside the efficacy and safety of anti-VEGFR tyrosine kinase inhibitors (TKIs) for GBM treatment.
METHODS
A comprehensive literature review was conducted using PubMed up to August 2023. Boolean operators and MeSH term "glioma," along with specific VEGFR-related keywords, were utilized following thorough examination of existing literature.
RESULTS
VEGFR correlates with glioma grade and GBM progression, presenting a viable therapeutic target. Regorafenib and axitinib show promise among studied TKIs. Other multi-targeted TKIs (MTKI) and combination therapies exhibit potential, albeit limited by blood-brain barrier penetration and toxicity. Combining treatments like radiotherapy and enhancing BBB penetration may benefit patients. Further research is warranted in patient quality of life and biomarker-guided selection.
CONCLUSION
While certain therapies hold promise for GBM, future research should prioritize personalized medicine and innovative strategies for improved treatment outcomes.
Topics: Humans; Glioblastoma; Protein Kinase Inhibitors; Receptors, Vascular Endothelial Growth Factor; Brain Neoplasms; Antineoplastic Agents
PubMed: 38677355
DOI: 10.1016/j.critrevonc.2024.104365 -
International Journal of Molecular... Apr 2024Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver conditions, and its progression is marked by evolution to non-alcoholic steatosis,... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver conditions, and its progression is marked by evolution to non-alcoholic steatosis, steatohepatitis, cirrhosis related to non-alcoholic steatohepatitis, and the potential occurrence of hepatocellular carcinoma. In our systematic review, we searched two databases, Medline (via Pubmed Central) and Scopus, from inception to 5 February 2024, and included 73 types of research (nine clinical studies and 64 pre-clinical studies) from 2854 published papers. Our extensive research highlights the impact of Berberine on NAFLD pathophysiology mechanisms, such as Adenosine Monophosphate-Activated Protein Kinase (AMPK), gut dysbiosis, peroxisome proliferator-activated receptor (PPAR), Sirtuins, and inflammasome. Studies involving human subjects showed a measurable reduction of liver fat in addition to improved profiles of serum lipids and hepatic enzymes. While current drugs for NAFLD treatment are either scarce or still in development or launch phases, Berberine presents a promising profile. However, improvements in its formulation are necessary to enhance the bioavailability of this natural substance.
Topics: Berberine; Non-alcoholic Fatty Liver Disease; Humans; Animals; Liver Cirrhosis; Liver
PubMed: 38673787
DOI: 10.3390/ijms25084201 -
Archives of Gynecology and Obstetrics Jun 2024Gynecologic perivascular epithelioid cell (PEC) tumors, or 'PEComas,' represent a rare and intriguing subset of tumors within the female reproductive tract. This... (Review)
Review
Gynecologic perivascular epithelioid cell (PEC) tumors, or 'PEComas,' represent a rare and intriguing subset of tumors within the female reproductive tract. This systematic literature review aims to provide an updated understanding of gynecologic PEComas based on available literature and data. Although PEComa is rare, there are varied tumor-site presentations across gynecologic organs, with uterine PEComas being the most prevalent. There is scarce high-quality literature regarding gynecologic PEComa, and studies on malignant PEComa underscore the challenges in diagnosis. Among the diverse mutations, mTOR alterations are the most prominent. Survival analysis reveals a high rate of local recurrence and metastatic disease, which commonly affects the lungs. Treatment strategies are limited, however mTOR inhibitors have pivotal role when indicated and chemotherapy may also be used. with some cases demonstrating promising responses. The paucity of data underscores the need for multicentric studies, an international registry for PEComas, and standardized reporting in case series to enhance clinical and pathological data.
Topics: Humans; Perivascular Epithelioid Cell Neoplasms; Female; Genital Neoplasms, Female; MTOR Inhibitors; Uterine Neoplasms; TOR Serine-Threonine Kinases; Neoplasm Recurrence, Local
PubMed: 38664269
DOI: 10.1007/s00404-024-07510-5 -
Annals of Hematology Jun 2024Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between... (Meta-Analysis)
Meta-Analysis
Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between JAK2V617F allele burden (also known as variant allele frequency) and the relevant clinical characteristics. Numerous studies have reported associations between allele burden and both hematologic and clinical features. While there are strong indications linking high allele burden in PV patients with symptoms and clinical characteristics, not all associations are definitive, and disparate and contradictory findings have been reported. Hence, this study aimed to synthesize existing data from the literature to better understand the association between JAK2V617F allele burden and relevant clinical correlates. Out of the 1,851 studies identified, 39 studies provided evidence related to the association between JAK2V617F allele burden and clinical correlates, and 21 studies were included in meta-analyses. Meta-analyses of correlation demonstrated that leucocyte and erythrocyte counts were significantly and positively correlated with JAK2V617F allele burden, whereas platelet count was not. Meta-analyses of standardized mean difference demonstrated that leucocyte and hematocrit were significantly higher in patients with higher JAK2V617F allele burden, whereas platelet count was significantly lower. Meta-analyses of odds ratio demonstrated that patients who had higher JAK2V617F allele burden had a significantly greater odds ratio for developing pruritus, splenomegaly, thrombosis, myelofibrosis, and acute myeloid leukemia. Our study integrates data from approximately 5,462 patients, contributing insights into the association between JAK2V617F allele burden and various hematological parameters, symptomatic manifestations, and complications. However, varied methods of data presentation and statistical analyses prevented the execution of high-quality meta-analyses.
Topics: Polycythemia Vera; Janus Kinase 2; Humans; Alleles; Gene Frequency; Amino Acid Substitution; Mutation, Missense
PubMed: 38652240
DOI: 10.1007/s00277-024-05754-4 -
Annals of Diagnostic Pathology Aug 2024Philadelphia (Ph) chromosome (9;22)(q34;q11) comprises 90-95 % of chronic myeloid leukemia (CML), while 5-10 % of CML have translocations involving three or more... (Review)
Review
Does presence of complex translocations involving BCR::ABL1 in chronic myeloid leukemia affect the response rate to tyrosine kinase inhibitors? A systematic review of the literature.
Philadelphia (Ph) chromosome (9;22)(q34;q11) comprises 90-95 % of chronic myeloid leukemia (CML), while 5-10 % of CML have translocations involving three or more chromosomes. The outcome of treating patients harbouring complex Ph-positive cytogenetics with tyrosine kinase inhibitors (TKI) is unclear. In the present systematic review, we aim to summarise the response of patients with complex Ph-positive cytogenetics to treatment with TKI therapy. We collated all available literature from databases such as PubMed, Google Scholar, Web of Science database, Cochrane library, Scopus and Embase (up until January 31st, 2024), which describe cases of patients with CML, harbouring complex Ph-positive variations (three and four-way translocations), and summarised their response to TKI therapy. The studies were screened for the following criteria: documented TKI intervention and outcome (whether CR was achieved). Studies that did not report the same, were excluded. Additionally, we report a case from our center of a 55-year-old patient with CML, positive for the Ph-chromosome, harbouring a three-way translocation involving chromosome 15 i.e. 46XX, t(9;15;22) (q34;p11;q11). Identification of BCR::ABL and involvement of chromosome 15 was carried out using conventional cytogenetics, fluorescence in situ hybridization (FISH), and quantitative PCR (qPCR). Based on the inclusion criteria, a total of 15 studies were included from which a total of 87 cases were covered. Overall, we identified 38 unique complex three- and four-way translocations across 87 Ph-positive cases and found that 85 patients with complex Ph-positive cytogenetics achieved complete remission upon treatment and did not appear to have a lesser response to TKI therapy.
Topics: Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Translocation, Genetic; Protein Kinase Inhibitors; Fusion Proteins, bcr-abl; Middle Aged; Philadelphia Chromosome; Treatment Outcome; Male; Female; Tyrosine Kinase Inhibitors
PubMed: 38636337
DOI: 10.1016/j.anndiagpath.2024.152303 -
Immunopharmacology and Immunotoxicology Jun 2024The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors.
METHOD
By searching PubMed, Web of Science, Cochrane, CNKI, Wanfang and other databases, all the literatures about the comparison of clinical efficacy of lenvatinib in the treatment of various solid tumors. According to the criteria of inclusion and exclusion of literature, two participants screened the literature, collated the data and evaluated the literature. RevMan 5.4 software was used for meta-analysis of the included literatures.
RESULTS
A total of 12 studies were included, including 5213 patients. Meta-analysis showed that, in terms of efficacy, the risk (HR) of prolonging PFS in the treatment of various solid tumors in the lenvatinib group was 1.91 times that in the control group (HR = 1.91, 95% CI: 1.58-2.31, < 0.00001), and the risk (HR) of prolonging OS was 1.27 times that in the single targeted drug group (HR = 1.27, 95% CI: 1.15-1.40, < 0.00001). In terms of safety, the risk of adverse events in the treatment of various solid tumors in the lenvatinib group was higher than that in the control group, especially in Endocrine Toxicities, Renal/Urinary Toxicities, Vascular Toxicities, Musculoskeletal/a Connective Tissue Toxicities and Metabolism/Nutrition Toxicities.
CONCLUSIONS
Lenvatinib in various solid tumors can prolong OS and disease PFS of patients, improve the clinical benefit rate and improve the quality of life of patients. At the same time, there is a certain incidence of adverse events, and symptomatic intervention should be given in clinical medication.
Topics: Humans; Antineoplastic Agents; Neoplasms; Phenylurea Compounds; Protein Kinase Inhibitors; Quinolines; Treatment Outcome
PubMed: 38627024
DOI: 10.1080/08923973.2024.2344153 -
European Journal of Surgical Oncology :... Jun 2024Mutations in the BRAF gene (BRAFmut) are associated with an unfavorable prognosis in patients with metastatic colorectal cancer (CRC). The aim of this meta-analysis was... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Mutations in the BRAF gene (BRAFmut) are associated with an unfavorable prognosis in patients with metastatic colorectal cancer (CRC). The aim of this meta-analysis was to evaluate the prognosis of colorectal cancer (CRC) patients with liver metastases and the potential benefits of liver resection in patients with BRAFmut CRC.
MATERIAL AND METHODS
A systematic search of PubMed, Cochrane Central Controlled Trials, and Embase databases was conducted on May 31, 2023. The inclusion criteria were as follows:1) reporting of outcomes in patients with BRAFmut CRC who underwent surgery for liver metastases and/or comparison of outcomes between those who underwent and those who did not undergo resection; 2) reporting of survival information as hazard ratios (HR); and 3) publication in English.
RESULTS
34 studies were included. Median follow up was 48 months for prognostic BRAF status meta-analysis. BRAFmut status showed a significantly increased risk of mortality (hazard ratio [HR] = 2.56, 95% confidence interval [CI] 2.04-3.22; P < 0.01) and relapse (HR = 1.97, 95% CI 1.44-2.71; P < 0.01). Resection of liver metastases was associated with a survival benefit (median follow up 46 months). The HR for survival was 0.44 (95% confidence interval [CI] 0.33-0.59; P < 0.01) in favor of surgery.
CONCLUSIONS
and Relevance: Our analysis indeed confirms that BRAF mutation is associated with poor survival outcomes after liver resection of CRC metastases. However, upon quantitatively assessing the survival benefit of surgical intervention in patients with BRAF-mutated CRC liver metastases, we identified a significant 56% reduction in the risk of death.
Topics: Humans; Proto-Oncogene Proteins B-raf; Colorectal Neoplasms; Liver Neoplasms; Mutation; Hepatectomy; Prognosis; Survival Rate
PubMed: 38603866
DOI: 10.1016/j.ejso.2024.108306 -
Translational Lung Cancer Research Mar 2024International guidelines recommend the use of local therapy (LT) to limited progression in patients with epidermal growth factor receptor (EGFR)-mutated advanced...
BACKGROUND
International guidelines recommend the use of local therapy (LT) to limited progression in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). However, the use of LT before disease progression has not been extensively analyzed. This meta-analysis evaluates the efficacy and safety of administering additional LT in conjunction with first-line EGFR-tyrosine kinase inhibitors (TKIs) before disease progression in patients with EGFR-mutated advanced NSCLC.
METHODS
We systematically searched PubMed, Embase, and the Cochrane Library for studies published up until May 31, 2023. The LT group consisted of patients who received first-line EGFR-TKIs in conjunction with additional LT, while the TKI group comprised participants treated with first-line EGFR-TKIs alone. Studies comparing the survival outcomes of the LT and TKI groups were included in this analysis. The primary outcomes were progression-free survival (PFS) and overall survival (OS). This review was registered on PROSPERO (registration number CRD42023439913).
RESULTS
Among the 11 investigated studies covering 1,313 patients, the LT modalities included radiotherapy, surgery, and ablation therapy, which accounted for 91%, 27%, and 27% of the studies, respectively. The pooled hazard ratios of median PFS and OS were 0.34 [95% confidence interval (CI): 0.22-0.53; P<0.001] and 0.42 (95% CI: 0.36-0.48; P<0.001), respectively, which indicated significant benefits for the LT group compared to the TKI group. There was no significant difference between the LT and TKI groups (P=0.473) regarding the incidence of grade 3 or higher adverse events.
CONCLUSIONS
This study suggests that the strategic use of additional LT before disease progression is a promising approach for the treatment of EGFR-mutated advanced NSCLC.
PubMed: 38601443
DOI: 10.21037/tlcr-23-830 -
Current Medical Research and Opinion May 2024The clinicopathological factors indicating risk of recurrence are used to guide the choice of perioperative therapy in patients with breast cancer. Although several risk... (Meta-Analysis)
Meta-Analysis Review
Risk factors for recurrence in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative early breast cancer in Japan: a systematic literature review and meta-analysis.
BACKGROUND
The clinicopathological factors indicating risk of recurrence are used to guide the choice of perioperative therapy in patients with breast cancer. Although several risk factors for recurrence have been reported in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer in Japan, there has been no systematic review quantifying potential risk factors.
METHODS
We performed a systematic literature review and meta-analysis using the MEDLINE, Embase, Cochrane CENTRAL, and Japan Medical Abstract Society databases to identify risk factors for recurrence in HR+/HER2- early breast cancer in Japan. The primary outcome was relapse-free or disease-free survival (RFS/DFS), and the secondary outcomes were overall survival and breast cancer-specific survival (BCSS).
RESULTS
Searches identified 42 eligible publications. Meta-analyses identified lymph node metastasis (hazard ratio: 2.76 [95% confidence interval: 1.97-3.88]), large tumor size (1.67 [1.24-2.23]), high histological grade (1.50 [1.04-2.16]), and high nuclear grade (2.02 [1.61-2.54]) as risk factors for RFS/DFS. Lymph node metastasis (2.43 [1.28-4.63]), large tumor size (1.80 [1.24-2.62]), and high histological grade (2.02 [1.44-2.84]) were also risk factors for overall survival, and high progesterone status was a possible favorable prognostic factor for BCSS (0.20 [0.10-0.42]).
CONCLUSIONS
Identified risk factors were consistent with the previous reports, and this study provides quantitative summary of risk factors for HR+/HER2- early breast cancer recurrence in Japan. (PROSPERO Registration ID, CRD42022338391.).
Topics: Humans; Breast Neoplasms; Female; Receptor, ErbB-2; Japan; Neoplasm Recurrence, Local; Risk Factors; Receptors, Progesterone; Receptors, Estrogen; Lymphatic Metastasis; Disease-Free Survival
PubMed: 38597173
DOI: 10.1080/03007995.2024.2332436