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Medicina (Kaunas, Lithuania) Dec 2023: Several recent randomized controlled trials (RCTs) have reported on the survival benefits of poly (ADP-ribose) polymerase inhibitors (PARPi) compared to... (Meta-Analysis)
Meta-Analysis Review
: Several recent randomized controlled trials (RCTs) have reported on the survival benefits of poly (ADP-ribose) polymerase inhibitors (PARPi) compared to standard-of-care (SOC) treatment (enzalutamide, abiraterone, or docetaxel) in patients with metastatic castration-resistant prostate cancer (mCRPC). However, there is a limited integrated analysis of high-quality evidence comparing the efficacy and safety of PARPi and SOC treatments in this context. : This study aims to comprehensively analyze the survival benefits and adverse events associated with PARPi and SOC treatments through a head-to-head meta-analysis in mCRPC. : A systematic review search was conducted in PubMed, Embase, Clinical trials, and the Central Cochrane Registry in July 2023. RCTs were assessed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The systematic review was prospectively registered on PROSPERO (CRD42023441034). : A total of 8 studies, encompassing 2341 cases in the PARPi treatment arm and 1810 cases in the controlled arm, were included in the qualitative synthesis. The hazard ratio (HR) for radiographic progression-free survival (rPFS) and overall survival (OS) were 0.74 (95% CI, 0.61-0.90) and 0.89 (95% CI, 0.80-0.99), respectively, in the intention-to-treatment patients. For subgroup analysis, HRs for rPFS and OS in the BRCA-mutated subgroup were 0.39 (95% CI, 0.28-0.55) and 0.62 (95% CI, 0.38-0.99), while in the HRR-mutated subgroup, HR for rPFS was 0.57 (95% CI, 0.48-0.69) and for OS was 0.77 (95% CI, 0.64-0.93). The odds ratio (OR) for all grades of adverse events (AEs) and AEs with severity of at least grade 3 were 3.86 (95% CI, 2.53-5.90) and 2.30 (95% CI, 1.63-3.26), respectively. : PARP inhibitors demonstrate greater effectiveness than SOC treatments in HRR/BRCA-positive patients with mCRPC. Further research is required to explore ways to reduce adverse event rates and investigate the efficacy of HRR/BRCA-negative patients.
Topics: Male; Humans; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms, Castration-Resistant; Ribose; Disease-Free Survival; Randomized Controlled Trials as Topic
PubMed: 38138301
DOI: 10.3390/medicina59122198 -
Acta Paediatrica (Oslo, Norway : 1992) Aug 2021To systematically review human metabolomic studies investigating metabolic responses in septic neonates. (Review)
Review
AIM
To systematically review human metabolomic studies investigating metabolic responses in septic neonates.
METHODS
A systematic literature search was performed in the databases MEDLINE, EMBASE and Cochrane library up to the 1st of January 2021. We included studies that assessed neonatal sepsis and the following outcomes; (1) change in the metabolism compared to healthy neonates and/or (2) metabolomics compared to traditional diagnostic tools of neonatal sepsis. The screened abstracts were independently considered for eligibility by two researchers.
PROSPERO ID
CRD42020164454.
RESULTS
The search identified in total 762 articles. Fifteen articles were assessed for eligibility. Four studies were included, with totally 78 neonates. The studies used different diagnostic criteria and had between 1 and 16 sepsis cases. All studies with bacterial sepsis found alterations in the glucose and lactate metabolism, reflecting possible redistribution of glucose consumption from mitochondrial oxidative phosphorylation to the lactate and pentose phosphate pathway. We also found signs of increased oxidative stress and fatty acid oxidation in sepsis cases.
CONCLUSION
We found signs of metabolomic signatures in neonatal sepsis. This may lead to better understanding of sepsis pathophysiology and detection of new candidate biomarkers. Results should be validated in large-scale multicentre studies.
Topics: Anti-Bacterial Agents; Humans; Infant, Newborn; Metabolomics; Neonatal Sepsis; Research Design; Sepsis
PubMed: 33851423
DOI: 10.1111/apa.15874 -
Journal of Gynecology Obstetrics and... Apr 2022This meta-analysis evaluated the correlation between poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) expression and prognosis in patients with ovarian cancer. (Meta-Analysis)
Meta-Analysis
PURPOSE
This meta-analysis evaluated the correlation between poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) expression and prognosis in patients with ovarian cancer.
METHODS
Eligible studies were extracted from the electronic databases of PubMed, Web of Science, and EMBASE until 1 August 2019. The included studies investigated the correlation between PARP expression and clinical outcomes in patients with ovarian cancer. Clinical outcomes are overall survival (OS) and progression free survival (PFS). The clinical data of patients, such as clinicopathologic characteristics and survival, were analyzed. The language was limited to English, and studies conducted at the cellular level, animal studies, and non-original research were excluded. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were used for this meta-analysis.
RESULTS
A total of 9 eligible studies involving 1230 patients were included in our meta-analysis. Based on the analysis, higher PARP expression was correlated with worse overall survival [OS] (HR,1.64; 95% CI, 1.08-2.49; P = 0.020) in the univariate analysis, whereas results from multivariate analysis indicated that PARP overexpression wasn't statistically associated with worse OS (HR, 1.36; 95% CI, 0.98-1.90; P = 0.069). Moreover, the pooled results revealed that patients with PARP overexpression were not associated with worse histologic grade (OR,2.22; 95% CI, 0.98-5.02; P = 0.06).
CONCLUSION
PARP overexpression maybe associated with poor prognosis and survival in patients with ovarian cancer. The patients with PARP over expression were not tended to have a worse histologic grade. Findings require further validation.
Topics: Adenosine Diphosphate; Adenosine Diphosphate Ribose; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Prognosis; Ribose
PubMed: 35218983
DOI: 10.1016/j.jogoh.2022.102344 -
Archives of Gynecology and Obstetrics Aug 2021To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy... (Meta-Analysis)
Meta-Analysis Review
Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors as maintenance therapy in women with newly diagnosed ovarian cancer: a systematic review and meta-analysis.
PURPOSE
To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy in women with newly diagnosed ovarian cancer, and to explore whether this therapy produces a survival benefit in a subgroup population with specific clinical characteristics.
METHODS
We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science and relevant clinical research registry platforms on October 1, 2019, and included randomized controlled trials (RCTs) that compared PARP inhibitors with placebo in women (aged ≥ 18 years) with newly diagnosed epithelial ovarian cancer.
RESULTS
We identified four RCTs with 3,070 participants. Compared with placebo, PARP inhibitor maintenance therapy showed a clinically significant benefit on progression free survival (PFS) in homologous recombination deficiency (HRD) positive population (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.29-0.53). In contrast, no clear differences were identified between the groups in the HRD negative population (HR, 0.83; 95% CI 0.67-1.03). Further, there was no clear difference between the groups in terms of other outcomes (overall survival, health-related quality of life, and adverse events).
CONCLUSIONS
PARP inhibitor maintenance therapy significantly prolongs the PFS of patients with newly diagnosed ovarian cancer, especially in HRD positive patients. The diagnostic test used to determine HRD status plays an important role in guiding PARP inhibitor maintenance therapy. Compared with placebo, the effect of PARP inhibitors on ovarian cancer was probably not affected by the International Federation of Gynecology and Obstetrics stage status, response to first-line chemotherapy, and residual macroscopic disease after debulking surgery.
Topics: Adenosine Diphosphate; Antineoplastic Agents; Carcinoma, Ovarian Epithelial; Female; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Ribose; Treatment Outcome
PubMed: 34021367
DOI: 10.1007/s00404-021-06070-2 -
Current Oncology (Toronto, Ont.) Dec 2023Preclinical and clinical studies have suggested potential synergies of combining poly (ADP-ribose) polymerase (PARP) inhibitors and novel hormonal therapies (NHT) for... (Review)
Review
Preclinical and clinical studies have suggested potential synergies of combining poly (ADP-ribose) polymerase (PARP) inhibitors and novel hormonal therapies (NHT) for patients with metastatic castration-resistant prostate cancer (mCRPC). We systematically searched PubMed, ClinicalTrials.gov and ASCO-GU annual meeting abstracts up to March 2023 to identify potential phase III trials reporting the use of combining PARP inhibitors with NHT in the first-line setting for mCRPC. A total of four phase III trials met the criteria for subsequent review. Emerging data suggested that the radiographic progression-free survival (rPFS) was significantly longer in the PARP inhibitor combined with NHT group versus the placebo plus NHT group for the first-line setting of biomarker-unselected mCRPC patients, especially for patients with homologous recombination repair (HRR) mutation (HRR m), and with the greatest benefit for BRCA1/2 mutation (BRCA1/2 m) populations. Final overall survival (OS) data of the PROpel trial indicated a significant improvement in median OS for mCRPC patients with HRR m and BRCA1/2 m receiving olaparib + abiraterone. Prior taxane-based chemotherapy might not influence the efficacy of the combination. Compared with the current standard-of-care therapies, combining NHT with PARP inhibitors could achieve a significant survival benefit in the first-line setting for mCRPC patients with HRR and BRCA1/2 mutations.
Topics: Male; Humans; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms, Castration-Resistant; BRCA1 Protein; Ribose; BRCA2 Protein; Antineoplastic Agents
PubMed: 38132385
DOI: 10.3390/curroncol30120751 -
Journal of Cancer Research and... Dec 2021To evaluate the efficacy, safety, and potential advantages of Poly (ADP-ribose) polymerase inhibitors (PARPi) in treating BRCA-mutated breast cancer, we performed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate the efficacy, safety, and potential advantages of Poly (ADP-ribose) polymerase inhibitors (PARPi) in treating BRCA-mutated breast cancer, we performed a meta-analysis of published studies.
MATERIALS AND METHODS
Four randomized controlled trials (RCTs) were included in the meta-analysis. Data analysis was conducted in Review Manager 5.4.
RESULTS
The progression-free survival (PFS) of the patients with triple-negative (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.74-0.88; P < 0.00001) or hormone receptor-positive (HR 0.83; 95% CI 0.77-0.91; P < 0.0001) BRCA-mutated breast cancer was significantly extended in the containing PARPi therapy arm versus the chemotherapy arm. PFS of the patients who did not receive platinum-based therapy (HR 0.78; 95% CI 0.70-0.86; P < 0.0001) was significantly extended in the PARPi monotherapy arm versus the chemotherapy arm. The objective response rate of patients treated by PARPi monotherapy (risk ratio [RR] 2.51; 95% CI 1.81-3.47; P < 0.00001) was significantly higher than that of patients treated by chemotherapy. The incidence of thrombocytopenia in patients received PARPi combined therapy was obviously increased compared with chemotherapy group (RR 1.36; 95% CI 1.07-1.72; P = 0.01). PARPi monotherapy markedly increased the incidence of anemia (RR 5.83; 95% CI 2.64-12.88; P < 0.0001) versus chemotherapy. However, the risk of neutropenia (RR 0.48; 95% CI 0.29-0.81; P = 0.006) was reduced in the PARPi monotherapy arm. There were no statistical differences in other adverse events among these three groups.
CONCLUSIONS
PARPi combined therapy and monotherapy improved PFS of patients with BRCA-mutated breast cancer compared with standard chemotherapy, which was unrelated to type of BRCA mutation and status of hormone receptor. PARPi therapy has slightly higher hematological toxicity and better overall safety and tolerance.
PROSPERO REGISTRATION NUMBER
CRD42020204385.
Topics: Adenosine Diphosphate; Breast Neoplasms; Female; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Progression-Free Survival; Ribose
PubMed: 35381738
DOI: 10.4103/jcrt.jcrt_2085_21 -
Applied Microbiology and Biotechnology Aug 2020Ribose-5-phosphate isomerase (Rpi, EC 5.3.1.6) is widespread in microorganisms, animals, and plants. It has a pivotal role in the pentose phosphate pathway and...
Ribose-5-phosphate isomerase (Rpi, EC 5.3.1.6) is widespread in microorganisms, animals, and plants. It has a pivotal role in the pentose phosphate pathway and responsible for catalyzing the isomerization between D-ribulose 5-phosphate and D-ribose 5-phosphate. In recent years, Rpi has received considerable attention as a multipurpose biocatalyst for production of rare sugars, including D-allose, L-rhamnulose, L-lyxose, and L-tagatose. Besides, it has been thought of as a potential drug target in the treatment of trypanosomatid-caused diseases such as Chagas' disease, leishmaniasis, and human African trypanosomiasis. Despite increased research activities, up to now, no systematic review of Rpi has been published. To fill this gap, this paper provides detailed information about the enzymatic properties of various Rpis. Furthermore, structural features, catalytic mechanism, and molecular modifications of Rpis are summarized based on extensive crystal structure research. Additionally, the applications of Rpi in rare sugar production and the role of Rpi in trypanocidal drug design are reviewed. Key points • Fundamental properties of various ribose-5-phosphate isomerases (Rpis). • Differences in crystal structure and catalytic mechanism between RpiA and RpiB. • Application of Rpi as a rare sugar producer and a potential drug target.
Topics: Aldose-Ketose Isomerases; Animals; Binding Sites; Biocatalysis; Crystallography, X-Ray; Humans; Isomerism; Kinetics; Models, Molecular; Parasitic Diseases; Plants; Ribosemonophosphates
PubMed: 32533303
DOI: 10.1007/s00253-020-10735-4 -
Asian Journal of Surgery Dec 2023
Meta-Analysis
Topics: Humans; Female; Poly(ADP-ribose) Polymerase Inhibitors; Ribose; Ovarian Neoplasms; Mutation
PubMed: 37541880
DOI: 10.1016/j.asjsur.2023.07.118 -
Frontiers in Genetics 2022infects millions and kills thousands of people annually the world over. With the emergence of artemisinin and/or multidrug resistant strains of the pathogen, it has...
infects millions and kills thousands of people annually the world over. With the emergence of artemisinin and/or multidrug resistant strains of the pathogen, it has become even more challenging to control and eliminate the disease. Multiomics studies of the parasite have started to provide a glimpse into the confounding genetics and mechanisms of artemisinin resistance and identified mutations in Kelch13 (K13) as a molecular marker of resistance. Over the years, thousands of genomes and transcriptomes of artemisinin-resistant/sensitive isolates have been documented, supplementing the search for new genes/pathways to target artemisinin-resistant isolates. This meta-analysis seeks to recap the genetic landscape and the transcriptional deregulation that demarcate artemisinin resistance in the field. To explore the genetic territory of artemisinin resistance, we use genomic single-nucleotide polymorphism (SNP) datasets from 2,517 isolates from 15 countries from the MalariaGEN Network (The Pf3K project, pilot data release 4, 2015) to dissect the prevalence, geographical distribution, and co-existing patterns of genetic markers associated with/enabling artemisinin resistance. We have identified several mutations which co-exist with the established markers of artemisinin resistance. Interestingly, K13-resistant parasites harbor α-ß hydrolase and putative HECT domain-containing protein genes with the maximum number of SNPs. We have also explored the multiple, publicly available transcriptomic datasets to identify genes from key biological pathways whose consistent deregulation may be contributing to the biology of resistant parasites. Surprisingly, glycolytic and pentose phosphate pathways were consistently downregulated in artemisinin-resistant parasites. Thus, this meta-analysis highlights the genetic and transcriptomic features of resistant parasites to propel further exploratory studies in the community to tackle artemisinin resistance.
PubMed: 35464842
DOI: 10.3389/fgene.2022.824483 -
Metabolomics : Official Journal of the... Mar 2018Bisphenol A (BPA), 2,2-bis(4-hydroxyphenyl) propane, a common industrial chemical which has extremely huge production worldwide, is ubiquitous in the environment. Human...
INTRODUCTION
Bisphenol A (BPA), 2,2-bis(4-hydroxyphenyl) propane, a common industrial chemical which has extremely huge production worldwide, is ubiquitous in the environment. Human have high risk of exposing to BPA and the health problems caused by BPA exposure have aroused public concern. However, the biomarkers for BPA exposure are lacking. As a rapidly developing subject, metabolomics has accumulated a large amount of valuable data in various fields. The secondary application of published metabolomics data could be a very promising field for generating novel biomarkers whilst further understanding of toxicity mechanisms.
OBJECTIVES
To summarize the published literature on the use of metabolomics as a tool to study BPA exposure and provide a systematic perspectives of current research on biomarkers screening of BPA exposure.
METHODS
We conducted a systematic search of MEDLINE (PubMed) up to the end of June 25, 2017 with the key term combinations of 'metabolomics', 'metabonomics', 'mass spectrometry', 'nuclear magnetic spectroscopy', 'metabolic profiling' and 'amino acid profile' combined with 'BPA exposure'. Additional articles were identified through searching the reference lists from included studies.
RESULTS
This systematic review included 15 articles. Intermediates of glycolysis, Krebs cycle, β oxidation of long chain fatty acids, pentose phosphate pathway, nucleoside metabolism, branched chain amino acid metabolism, aromatic amino acids metabolism, sulfur-containing amino acids metabolism were significantly changed after BPA exposure, suggesting BPA had a highly complex toxic effects on organism which was consistent with existing studies. The biomarkers most consistently associated with BPA exposure were lactate and choline.
CONCLUSION
Existing metabolomics studies of BPA exposure present heterogeneous findings regarding metabolite profile characteristics. We need more evidence from target metabolomics and epidemiological studies to further examine the reliability of these biomarkers which link to low, environmentally relevant, exposure of BPA in human body.
Topics: Benzhydryl Compounds; Biomarkers; Humans; Metabolomics; Phenols
PubMed: 30830327
DOI: 10.1007/s11306-018-1342-z