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Urologia Feb 2024The major barriers to phytonutrients in prostate cancer therapy are non-specific mechanisms and bioavailability issues. Studies have pointed to a synergistic combination... (Review)
Review
The major barriers to phytonutrients in prostate cancer therapy are non-specific mechanisms and bioavailability issues. Studies have pointed to a synergistic combination of curcumin (CURC) and ursolic acid (UA). We investigate this combination using a systematic review process to assess the most likely mechanistic pathway and human testing in prostate cancer. We used the PRISMA statement to screen titles, abstracts, and the full texts of relevant articles and performed a descriptive analysis of the literature reviewed for study inclusion and consensus of the manuscript. The most common molecular and cellular pathway from articles reporting on the pathways and effects of CURC ( = 173) in prostate cancer was NF-κB ( = 25, 14.5%). The most common molecular and cellular pathway from articles reporting on the pathways and effects of UA ( = 24) in prostate cancer was caspase 3/caspase 9 ( = 10, 41.6%). The three most common molecular and cellular pathway from articles reporting on the pathways and effects of both CURC and UA ( = 193) in prostate cancer was NF-κB ( = 28, 14.2%), Akt ( = 22, 11.2%), and androgen ( = 19, 9.6%). Therefore, we have identified the potential synergistic target pathways of curcumin and ursolic acid to involve NF-κB, Akt, androgen receptors, and apoptosis pathways. Our review highlights the limited human studies and specific effects in prostate cancer.
Topics: Male; Humans; Ursolic Acid; Curcumin; NF-kappa B; Signal Transduction; Proto-Oncogene Proteins c-akt; Apoptosis; Triterpenes; Prostatic Neoplasms
PubMed: 37776274
DOI: 10.1177/03915603231202304 -
Radiotherapy and Oncology : Journal of... Sep 2023In recent years, the treatment landscape for breast cancer has undergone significant advancements, with the introduction of several new anticancer agents. One such agent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
In recent years, the treatment landscape for breast cancer has undergone significant advancements, with the introduction of several new anticancer agents. One such agent is trastuzumab emtansine (T-DM1), an antibody drug conjugate that has shown improved outcomes in both early and advanced breast cancer. However, there is currently a lack of comprehensive evidence regarding the safety profile of combining T-DM1 with radiation therapy (RT). In this study, we aim to provide a summary of the available data on the safety of combining RT with T-DM1 in both early and metastatic breast cancer settings.
MATERIALS AND METHODS
This systematic review and meta-analysis project is part of the consensus recommendations by the European Society for Radiotherapy and Oncology (ESTRO) Guidelines Committee on integrating RT with targeted treatments for breast cancer. A thorough literature search was conducted using the PUBMED/MedLine, Embase, and Cochrane databases to identify original studies focusing on the safety profile of combining T-DM1 with RT.
RESULTS
After applying eligibility criteria, nine articles were included in the meta-analysis. Pooled data from these studies revealed a high incidence of grade 3 + radionecrosis (17%), while the rates of grade 3 + radiation-related pneumonitis (<1%) and skin toxicity (1%) were found to be very low.
CONCLUSION
Although there is some concern regarding a slight increase in pneumonitis when combining T-DM1 with postoperative RT, the safety profile of this combination was deemed acceptable for locoregional treatment in non-metastatic breast cancer. However, caution is advised when irradiating intracranial sites concurrently with T-DM1. There is a pressing need for international consensus guidelines regarding the safety considerations of combining T-DM1 and RT for breast cancer.
Topics: Humans; Female; Ado-Trastuzumab Emtansine; Trastuzumab; Receptor, ErbB-2; Antibodies, Monoclonal, Humanized; Maytansine; Treatment Outcome; Breast Neoplasms
PubMed: 37437610
DOI: 10.1016/j.radonc.2023.109805 -
Eye (London, England) Jan 2023This study aimed to compare efficacy and treatment burden of treat-and-extend (T&E) anti-VEGF against fixed and pro re nata (PRN) regimens for neovascular age-related... (Meta-Analysis)
Meta-Analysis Review
This study aimed to compare efficacy and treatment burden of treat-and-extend (T&E) anti-VEGF against fixed and pro re nata (PRN) regimens for neovascular age-related macular degeneration (nAMD). MEDLINE, CENTRAL, and EMBASE were searched. Randomized-controlled trials and observational studies comparing T&E to PRN or fixed dosing for treatment-naïve AMD patients were included. Mean difference (MD) for visual acuity (VA) and number of injections are presented. Risk of bias was assessed according to Cochrane guidelines. Methodology was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). VA improvement was similar with T&E and fixed dosing at one (MD -0.08 letters, p = 0.95) and two years (MD 0.58 letters, p = 0.62). In contrast, VA improvements were significantly greater for T&E when compared against a PRN regimen at one (MD 3.95 letters, p < 0.0001) and two years (MD 4.08 letters, p < 0.001). Significantly fewer ranibizumab injections were administered in the T&E arm at one (MD -2.42 injections, p < 0.0001) and two years (MD -6.06 injections, p < 0.00001) relative to fixed dosing. Fewer aflibercept injections were likewise administered to patients on a T&E regimen versus fixed dosing at one year (MD -0.78 injections, p < 0.0001). Low-certainty evidence from the present synthesis implies that T&E preserves VA similar to fixed schedules with significantly fewer injections at one and two years. Also, patients with T&E dosing achieved better VA outcomes than those on PRN regimen but T&E dosing was associated with more injections.
Topics: Humans; Angiogenesis Inhibitors; Vascular Endothelial Growth Factor A; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Clinical Protocols; Intravitreal Injections; Treatment Outcome; Recombinant Fusion Proteins; Wet Macular Degeneration; Randomized Controlled Trials as Topic
PubMed: 35396574
DOI: 10.1038/s41433-022-02020-7 -
Journal of Cachexia, Sarcopenia and... Feb 2022Sarcopenic obesity is a distinct condition of sarcopenia in the context of obesity, with the cumulative health risks of both phenotypes. Differential expression of... (Review)
Review
Sarcopenic obesity is a distinct condition of sarcopenia in the context of obesity, with the cumulative health risks of both phenotypes. Differential expression of microRNAs (miRNAs) has been reported separately in people with obesity and sarcopenia and may play a role in the pathogenesis of sarcopenic obesity. However, this has not been explored to date. This study aimed to identify differentially expressed miRNAs reported in serum, plasma, and skeletal muscle of people with obesity and sarcopenia and whether there are any commonalities between these conditions. We performed a systematic review on Embase and MEDLINE (PROSPERO, CRD42020224486) for differentially expressed miRNAs (fold change >1.5 or P-value <0.05) in (i) sarcopenia or frailty and (ii) obesity or metabolic syndrome. The functions and targets of miRNAs commonly changed in both conditions, in the same direction, were searched using PubMed. Following deduplication, 247 obesity and 42 sarcopenia studies were identified for full-text screening. Screening identified 36 obesity and 6 sarcopenia studies for final inclusion. A total of 351 miRNAs were identified in obesity and 157 in sarcopenia. Fifty-five miRNAs were identified in both obesity and sarcopenia-by sample type, 48 were found in plasma and one each in serum and skeletal muscle. Twenty-four miRNAs were identified from 10 of the included studies as commonly changed in the same direction (22 in plasma and one each in serum and skeletal muscle) in obesity and sarcopenia. The majority of miRNA-validated targets identified in the literature search were members of the phosphoinositide 3-kinase/protein kinase B and transforming growth factor-β signalling pathways. The most common targets identified were insulin-like growth factor 1 (miR-424-5p, miR-483-3p, and miR-18b-5p) and members of the SMAD family (miR-483-3p, miR-92a-3p, and miR-424-5p). The majority of commonly changed miRNAs were involved in protein homeostasis, mitochondrial dynamics, determination of muscle fibre type, insulin resistance, and adipogenesis. Twenty-four miRNAs were identified as commonly dysregulated in obesity and sarcopenia with functions and targets implicated in the pathogenesis of sarcopenic obesity. Given the adverse health outcomes associated with sarcopenic obesity, understanding the pathogenesis underlying this phenotype has the potential to lead to effective screening, monitoring, or treatment strategies. Further research is now required to confirm whether these miRNAs are differentially expressed in older adults with sarcopenic obesity.
Topics: Adipogenesis; Aged; Humans; MicroRNAs; Obesity; Phosphatidylinositol 3-Kinases; Sarcopenia
PubMed: 34984856
DOI: 10.1002/jcsm.12878 -
Journal of Infection and Public Health Sep 2021To systematically investigate the relationship between cardiac biomarkers and COVID-19 severity and mortality. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically investigate the relationship between cardiac biomarkers and COVID-19 severity and mortality.
METHODS
We performed a literature search using PubMed, Web of Science, and Google Scholar. The standardized mean difference (SMD) and 95% confidence interval (CI) were applied to estimate the combined results of 67 studies. A meta-analysis of cardiac biomarkers was used to evaluate disease mortality and severity in COVID-19 patients.
RESULTS
A meta-analysis of 7812 patients revealed that patients with high levels of cardiac troponin I (SMD = 0.81 U/L, 95% CI = 0.14-1.48, P = 0.017), cardiac troponin T (SMD = 0.78 U/L, 95% CI = 0.07-1.49, P = 0.032), high-sensitive cardiac troponin I (SMD = 0.66 pg/mL, 95% CI = 0.51-0.81, P < 0.001), high-sensitive cardiac troponin T (SMD = 0.93 U/L, 95% CI = 0.21-1.65, P = 0.012), creatine kinase-MB (SMD = 0.54 U/L, 95% CI = 0.39-0.69, P < 0.001), and myoglobin (SMD = 0.80 U/L, 95% CI = 0.57-1.03, P < 0.001) were associated with prominent disease severity in COVID-19 infection. Moreover, 9532 patients with a higher serum level of cardiac troponin I (SMD = 0.51 U/L, 95% CI = 0.37-0.64, P < 0.001), high-sensitive cardiac troponin (SMD = 0.51 ng/L, 95% CI = 0.29-0.73, P < 0.001), high-sensitive cardiac troponin I (SMD = 0.51 pg/mL, 95% CI = 0.38-0.63, P < 0.001), high-sensitive cardiac troponin T (SMD = 0.85 U/L, 95% CI = 0.63-1.07, P < 0.001), creatine kinase-MB (SMD = 0.48 U/L, 95% CI = 0.32-0.65, P < 0.001), and myoglobin (SMD = 0.55 U/L, 95% CI = 0.45-0.65, P < 0.001) exhibited a prominent level of mortality from COVID-19 infection.
CONCLUSION
Cardiac biomarkers (cardiac troponin I, cardiac troponin T, high-sensitive cardiac troponin, high-sensitive cardiac troponin I, high-sensitive cardiac troponin T, creatine kinase-MB, and myoglobin) should be more frequently applied in identifying high-risk COVID-19 patients so that timely treatment can be implemented to reduce severity and mortality in COVID-19 patients.
Topics: Biomarkers; COVID-19; Creatine Kinase, MB Form; Humans; Myoglobin; Severity of Illness Index; Troponin I; Troponin T
PubMed: 34416596
DOI: 10.1016/j.jiph.2021.07.016 -
Cancer Treatment Reviews Apr 2023The anti-tumor activity of WEE1 inhibitors (WEE1i) in gynecological malignancies has recently been demonstrated in clinical trials and its rationale is based on... (Review)
Review
INTRODUCTION
The anti-tumor activity of WEE1 inhibitors (WEE1i) in gynecological malignancies has recently been demonstrated in clinical trials and its rationale is based on biological/molecular features of gynecological cancers. With this systematic review, we aim to outline the clinical development and current evidence regarding the efficacy and safety of these targeted agents in in this patient group.
METHODS
Systematic literature review of trials including patients with gynecological cancers treated with a WEE1i. The primary objective was to summarize the efficacy of WEE1i in gynecological malignancies regarding objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and progression-free survival (PFS). Secondary objectives included toxicity profile, Maximum Tolerated Dose (MTD), pharmacokinetics, drug-drug interactions and exploratory objectives such as biomarkers for response.
RESULTS
26 records were included for data extraction. Almost all trials used the first-in-class WEE1i adavosertib; one conference abstract reported about Zn-c3. The majority of the trials included diverse solid tumors (n = 16). Six records reported efficacy results of WEE1i in gynecological malignancies (n = 6). Objective response rates of adavosertib monotherapy or in combination with chemotherapy ranged between 23% and 43% in these trials. Median PFS ranged from 3.0 to 9.9 months. The most common adverse events were bone marrow suppression, gastrointestinal toxicities and fatigue. Mainly alterations in cell cycle regulator genes TP53 and CCNE1 were potential predictors of response.
CONCLUSION
This report summarizes encouraging clinical development of WEE1i in gynecological cancers and considers its application in future studies. Biomarker-driven patient selection might be essential to increase the response rates.
Topics: Female; Humans; Genital Neoplasms, Female; Antineoplastic Agents; Protein-Tyrosine Kinases; Cell Cycle Proteins
PubMed: 36893690
DOI: 10.1016/j.ctrv.2023.102531 -
International Journal of Molecular... Nov 2023Studying primary melanoma and its corresponding metastasis has twofold benefits. Firstly, to better understand tumor biology, and secondly, to determine which sample... (Meta-Analysis)
Meta-Analysis Review
Studying primary melanoma and its corresponding metastasis has twofold benefits. Firstly, to better understand tumor biology, and secondly, to determine which sample should be examined in assessing drug targets. This study systematically analyzed all the literature on primary melanoma and its matched metastasis. Following PRISMA guidelines, we searched multiple medical databases for relevant publications from January 2000 to December 2022, assessed the quality of the primary-level studies using the QUIPS tool, and summarized the concordance rate of the most reported genes using the random-effects model. Finally, we evaluated the inter-study heterogeneity using the subgroup analysis. Thirty-one studies investigated the concordance of and in 1220 and 629 patients, respectively. The pooled concordance rate was 89.4% [95% CI: 84.5; 93.5] for and 97.8% [95% CI: 95.8; 99.4] for . When high-quality studies were considered, only mutation status consistency increased. Five studies reported the concordance status of c (93%, 44 patients) and promoter (64%, 53 patients). Lastly, three studies analyzed the concordance of cancer genes involved in the signaling pathways, apoptosis, and proliferation, such as (25%, four patients), (44%, nine patients), and (20%, five patients). Our study found that the concordance of known drug targets (mainly ) during melanoma progression is higher than in previous meta-analyses, likely due to advances in molecular techniques. Furthermore, significant heterogeneity exists in the genes involved in the melanoma genetic makeup; although our results are based on small patient samples, more research is necessary for validation.
Topics: Humans; Melanoma; Skin Neoplasms; Proto-Oncogene Proteins B-raf; Mutation; Melanoma, Cutaneous Malignant
PubMed: 38003476
DOI: 10.3390/ijms242216281 -
Breast (Edinburgh, Scotland) Jun 2023Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant, adjuvant, and metastatic settings, including for parenchymal brain metastases, their efficacy for patients with LM has not been studied in a randomized controlled trial. However, several single-armed prospective studies, case series and case reports have studied oral, intravenous, or intrathecally administered HER2-targeted therapy regimens for patients with HER2+ BC LM.
METHODS
We conducted a systematic review and meta-analysis of individual patient data to evaluate the efficacy of HER2-targeted therapies in HER2+ BC LM in accordance with PRISMA guidelines. Targeted therapies evaluated were trastuzumab (intrathecal or intravenous), pertuzumab, lapatinib, neratinib, tucatinib, trastuzumab-emtansine and trastuzumab-deruxtecan. The primary endpoint was overall survival (OS), with CNS-specific progression-free survival (PFS) as a secondary endpoint.
RESULTS
7780 abstracts were screened, identifying 45 publications with 208 patients, corresponding to 275 lines of HER2-targeted therapy for BC LM which met inclusion criteria. In univariable and multivariable analyses, we observed no significant difference in OS and CNS-specific PFS between intrathecal trastuzumab compared to oral or intravenous administration of HER2-targeted therapy. Anti-HER2 monoclonal antibody-based regimens did not demonstrate superiority over HER2 tyrosine kinase inhibitors. In a cohort of 15 patients, treatment with trastuzumab-deruxtecan was associated with prolonged OS compared to other HER2-targeted therapies and compared to trastuzumab-emtansine.
CONCLUSIONS
The results of this meta-analysis, comprising the limited data available, suggest that intrathecal administration of HER2-targeted therapy for patients with HER2+ BC LM confers no additional benefit over oral and/or IV treatment regimens. Although the number of patients receiving trastuzumab deruxtecan in this cohort is small, this novel agent offers promise for this patient population and requires further investigation in prospective studies.
Topics: Female; Humans; Ado-Trastuzumab Emtansine; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Prospective Studies; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Trastuzumab; Meningeal Neoplasms
PubMed: 37156650
DOI: 10.1016/j.breast.2023.04.008 -
European Journal of Medical Research Aug 2023The aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC).
METHODS
We conducted a systematic review and meta-analysis to aggregate the clinical outcomes of patients with LM from EGFR-mutant NSCLC treated with osimertinib. A comprehensive literature search for published and unpublished studies was implemented in April 2021 of PubMed, EMBASE, the Cochrane Library, and several international conference databases, in accordance with the PRISMA guidelines. Meta-analysis of proportions was conducted to calculate the pooled rate of overall response rate (ORR), disease control rate (DCR), one-year overall survival (OS), and adverse events (AEs).
RESULTS
A total of eleven studies (five prospective and six retrospective) including 353 patients were included. The majority of patients (346/353, 98.0%) received osimertinib as ≥ 2nd-line treatment for LM, either at a dosage of 80 mg (161/353, 45.6%) or 160 mg (191/353, 54.1%). The pooled rates of ORR and DCR were 42% (95% CI 24% to 59%) and 93% (95% CI 88% to 97%), respectively. The pooled one-year OS rate was 59% (95% CI 53% to 65%) in 233 patients from five studies. The highest incidence of AEs of all grades was rash (53%), followed by diarrhea (45%), paronychia (35%), decreased appetite (35%), and dry skin (27%), based on data from four studies.
CONCLUSIONS
Our study highlighted and confirmed the meaningful efficacy and a manageable safety profile of osimertinib for the treatment of LM from EGFR-mutant advanced NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Retrospective Studies; Prospective Studies; Antineoplastic Agents; ErbB Receptors; Protein Kinase Inhibitors; Mutation
PubMed: 37542339
DOI: 10.1186/s40001-023-01219-y -
Frontiers in Immunology 2023Autophagy in osteoarthritis (OA) has become an active area of research with substantial value and potential. Nevertheless, few bibliometric studies have systematically...
BACKGROUND
Autophagy in osteoarthritis (OA) has become an active area of research with substantial value and potential. Nevertheless, few bibliometric studies have systematically analyzed the available research in the field. The main goal of this study was to map the available literature on the role of autophagy in OA and identify global research hotspots and trends.
METHODS
The Web of Science Core Collection and Scopus databases were interrogated for studies of autophagy in OA published between 2004 and 2022. Microsoft Excel, VOSviewer and CiteSpace software were used to analyze and visualize the number of publications and associated citations, and reveal global research hotspots and trends in the autophagy in OA field.
RESULTS
732 outputs published by 329 institutions from 55 countries/regions were included in this study. From 2004 to 2022, the number of publications increased. China produced the most publications (n=456), prior to the USA (n=115), South Korea (n=33), and Japan (n=27). Scripps Research Institute (n=26) was the most productive institution. Martin Lotz (n=30) was the highest output author, while Caramés B (n=302) was the highest output author. was the most prolific and most co-cited journal. Currently, the autophagy in OA research hotspots include chondrocyte, transforming growth factor beta 1 (TGF-β1), inflammatory response, stress, and mitophagy. The emerging research trends in this field are AMPK, macrophage, senescence, apoptosis, tougu xiaotong capsule (TXC), green tea extract, rapamycin, and dexamethasone. Novel drugs targeting specific molecule such as TGF-β and AMPK have shown therapeutic potential but are still in the preclinical stage of development.
CONCLUSIONS
Research on the role of autophagy in OA is flourishing. Martin Lotz, Beatriz Caramés, and have made outstanding contributions to the field. Prior studies of OA autophagy mainly focused on mechanisms underlying OA and autophagy, including AMPK, macrophages, TGF-β1, inflammatory response, stress, and mitophagy. Emerging research trends, however, are centered around the relationship between autophagy, apoptosis, and senescence, as well as drug candidates such as TXC and green tea extract. The development of new targeted drugs that enhance or restore autophagic activity is a promising strategy for the treatment of OA.
Topics: Transforming Growth Factor beta1; AMP-Activated Protein Kinases; Autophagy; Antioxidants; Bibliometrics; Biological Products; Tea
PubMed: 36969240
DOI: 10.3389/fimmu.2023.1063018