-
European Journal of Medicinal Chemistry Jan 2024Prostate specific membrane antigen (PSMA) has been the subject of several studies in recent decades as a promising molecular target for prostate cancer (PCa), in fact it... (Review)
Review
Prostate specific membrane antigen (PSMA) has been the subject of several studies in recent decades as a promising molecular target for prostate cancer (PCa), in fact it is considered an excellent molecular target for both PCa imaging (both for staging and follow-up), by means of PET/CT and for radioligand therapy. Its interesting molecular features have enabled the development of a new diagnostic and therapeutic approach for PCa, called "theranostics." Considering the abundance of PSMA-based probes that have appeared so far in the literature, the present work focuses the attention on radiopharmaceuticals with increasing clinical application, highlighting advantages and disadvantages in terms of different metabolization and excretion processes, pharmacokinetic, binding affinity and variable internalization rate, tumor-to-background ratio, residence times and toxicity profile.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Radiopharmaceuticals; Precision Medicine; Gallium Radioisotopes
PubMed: 37992520
DOI: 10.1016/j.ejmech.2023.115966 -
Expert Opinion on Investigational Drugs Jan 2024Severe asthma patients often remain uncontrolled despite high-intensity therapies. Biological therapies targeting thymic stromal lymphopoietin (TSLP), a key player in... (Review)
Review
INTRODUCTION
Severe asthma patients often remain uncontrolled despite high-intensity therapies. Biological therapies targeting thymic stromal lymphopoietin (TSLP), a key player in asthma pathogenesis, have emerged as potential options. Currently, the only TSLP inhibitor approved for the treatment of severe asthma is the immunoglobulin G (IgG) 2λ anti-TSLP monoclonal antibody (mAb) tezepelumab.
AREAS COVERED
This systematic review assesses the efficacy and safety of investigational TSLP inhibitors across different stages of development for asthma treatment.
EXPERT OPINION
TSLP contributes to airway inflammation, making it a pivotal therapeutic target. Ecleralimab, an inhaled antibody fragment antigen binding, shows promising evidence in enhancing efficacy and reducing systemic adverse events. SAR443765, with its NANOBODY® formulation and bispecific inhibition of TSLP and IL-13, offers improved tissue penetration and efficacy. The mAB TQC2731 exhibits high in vitro bioactivity, and the strength of the mAb UPB-101 is to act against the TSLP receptor. Some studies include mild and moderate asthma patients, suggesting the potential for extending biological therapy to non-severe patients. This systematic review highlights the potential of TSLP inhibitors as valuable additions to asthma treatment, even in milder forms of the disease. Future research and cost-reduction efforts are needed to expanding access to these promising therapies.
Topics: Humans; Thymic Stromal Lymphopoietin; Asthma; Cytokines; Inflammation; Antibodies, Monoclonal
PubMed: 38206116
DOI: 10.1080/13543784.2024.2305144 -
Cancer Epidemiology, Biomarkers &... Jul 2023Sex hormones may influence the development of gastrointestinal cancer, but evidence is inconsistent. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sex hormones may influence the development of gastrointestinal cancer, but evidence is inconsistent.
METHODS
We systematically searched MEDLINE and Embase databases to identify prospective studies examining associations between prediagnostic circulating levels of sex hormones and risk of five gastrointestinal cancers: esophageal, gastric, liver, pancreatic, and colorectal cancer. Pooled ORs and 95% confidence intervals (95% CI) were calculated using random-effects models.
RESULTS
Among 16,879 identified studies, 29 were included (11 cohort, 15 nested case-control, and three case-cohort studies). Comparing the highest versus lowest tertiles, levels of most sex hormones were not associated with the studied tumors. Higher levels of sex hormone binding globulin (SHBG) were associated with increased risk of gastric cancer (OR = 1.35; 95% CI, 1.06-1.72), but such associations were restricted in men only (OR = 1.43; 95% CI, 1.10-1.85) when stratified by sex. Higher SHBG levels were associated with increased risk of liver cancer (OR = 2.07; 95% CI, 1.40-3.06). Higher testosterone levels were associated with increased risk of liver cancer overall (OR = 2.10; 95% CI, 1.48-2.96), particularly in men (OR = 2.63; 95% CI, 1.65-4.18), Asian populations (OR = 3.27; 95% CI, 1.57-6.83), and in hepatitis B surface antigen-positive individuals (OR = 3.90; 95% CI, 1.43-10.64). Higher levels of SHBG and testosterone were associated with decreased risk of colorectal cancer in men (OR = 0.89; 95% CI, 0.80-0.98 and OR = 0.88; 95% CI, 0.80-0.97, respectively) but not in women.
CONCLUSIONS
Circulating levels of SHBG and testosterone may influence the risk of gastric, liver, and colorectal cancer.
IMPACT
Further clarifying the role of sex hormones in the development of gastrointestinal cancer may unravel future novel targets for prevention and treatment.
Topics: Male; Humans; Female; Prospective Studies; Risk Factors; Gonadal Steroid Hormones; Testosterone; Gastrointestinal Neoplasms; Liver Neoplasms; Colorectal Neoplasms; Sex Hormone-Binding Globulin; Estradiol
PubMed: 37104672
DOI: 10.1158/1055-9965.EPI-23-0039 -
International Journal of Infectious... Sep 2023To assess the evidence on the presence of antibodies cross-reactive with SARS-CoV-2 antigens in prepandemic samples from African populations. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the evidence on the presence of antibodies cross-reactive with SARS-CoV-2 antigens in prepandemic samples from African populations.
METHODS
We performed a systematic review and meta-analysis of studies evaluating prepandemic African samples using pre-set assay-specific thresholds for SARS-CoV-2 seropositivity.
RESULTS
In total, 26 articles with 156 datasets were eligible, including 3437 positives among 29,923 measurements (11.5%) with large between-dataset heterogeneity. Positivity was similar for anti-nucleocapsid (14%) and anti-spike antibodies (11%), higher for anti-spike1 (23%), and lower for anti-receptor-binding domain antibodies (7%). Positivity was similar, on average, for immunoglobulin M and immunoglobulin G. Positivity was seen prominently in countries where malaria transmission occurs throughout and in datasets enriched in malaria cases (14%, 95% confidence interval, 12-15% vs 2%, 95% confidence interval 1-2% in other datasets). Substantial SARS-CoV-2 reactivity was seen in high malaria burden with or without high dengue burden (14% and 12%, respectively), and not without high malaria burden (2% and 0%, respectively). Lower SARS-CoV-2 cross-reactivity was seen in settings of high HIV seroprevalence. More sparse individual-level data showed associations of higher SARS-CoV-2 cross-reactivity with Plasmodium parasitemia and lower SARS-CoV-2 cross-reactivity with HIV seropositivity.
CONCLUSION
Prepandemic samples from Africa show high levels of anti-SARS-CoV-2 seropositivity. At the country level, cross-reactivity tracks especially with malaria prevalence.
Topics: Humans; Immunity, Humoral; Seroepidemiologic Studies; COVID-19; SARS-CoV-2; Africa; Immunoglobulin G; Antibodies, Viral
PubMed: 37327857
DOI: 10.1016/j.ijid.2023.06.009 -
American Journal of Reproductive... Dec 2023The immune system plays an essential role in embryonic implantation and pregnancy, but the molecular details remain controversial. In the past four decades, human... (Meta-Analysis)
Meta-Analysis Review
PROBLEM
The immune system plays an essential role in embryonic implantation and pregnancy, but the molecular details remain controversial. In the past four decades, human leukocyte antigen (HLA)-G and -F have garnered significant attention.
METHOD OF STUDY
MEDLINE, EMBASE, Web of Science, and the Cochrane Trials Registry were searched from their inception dates until December 2022. Studies were selected following PRISMA guidelines. Meta-analyses were used to assess the relationship of soluble HLA-G (sHLA-G) and HLA-G 3'-untranslated region polymorphisms with recurrent miscarriage (RM) and recurrent implantation failure (RIF). Narrative synthesis was conducted to determine the association of RM with other single nucleotide polymorphisms (SNPs) and HLA-G protein in tissues and of RIF with HLA-F. Risk-of-bias was assessed using ROBINS-I. Publication bias was assessed using Egger's and Begg's tests.
RESULTS
Finally, 42 articles were eligible for inclusion in the systematic review (32 in the meta-analysis; 13 in narrative synthesis). We found a significant association between the 14-bp ins/del HLA-G polymorphism and RM risk, but no definitive association with RIF risk. Women with RM had lower blood concentrations of sHLA-G during pregnancy and non-pregnancy than did controls. For women in the RIF group, no significant difference was found.
CONCLUSION
HLA-G protein and gene expression levels may be closely related to RM. The relevance of HLA-G to RIF is still being determined. A narrative synthesis of current studies has shown that HLA-F is likely associated with RIF.
Topics: Pregnancy; Humans; Female; HLA-G Antigens; Embryo Implantation; Polymorphism, Single Nucleotide; Abortion, Habitual; GTP-Binding Proteins
PubMed: 38009058
DOI: 10.1111/aji.13792 -
European Journal of Clinical... Apr 2024Long COVID is highly heterogeneous, often debilitating, and may last for years after infection. The aetiology of long COVID remains uncertain. Examination of potential... (Review)
Review
BACKGROUND
Long COVID is highly heterogeneous, often debilitating, and may last for years after infection. The aetiology of long COVID remains uncertain. Examination of potential serological markers of long COVID, accounting for clinical covariates, may yield emergent pathophysiological insights.
METHODS
In adherence to PRISMA guidelines, we carried out a rapid review of the literature. We searched Medline and Embase for primary observational studies that compared IgG response in individuals who experienced COVID-19 symptoms persisting ≥12 weeks post-infection with those who did not. We examined relationships between serological markers and long COVID status and investigated sources of inter-study variability, such as severity of acute illness, long COVID symptoms assessed and target antigen(s).
RESULTS
Of 8018 unique records, we identified 29 as being eligible for inclusion in synthesis. Definitions of long COVID varied. In studies that reported anti-nucleocapsid (N) IgG (n = 10 studies; n = 989 participants in aggregate), full or partial anti-Spike IgG (i.e. the whole trimer, S1 or S2 subgroups, or receptor binding domain, n = 19 studies; n = 2606 participants), or neutralizing response (n = 7 studies; n = 1123 participants), we did not find strong evidence to support any difference in serological markers between groups with and without persisting symptoms. However, most studies did not account for severity or level of care required during acute illness, and other potential confounders.
CONCLUSIONS
Pooling of studies would enable more robust exploration of clinical and serological predictors among diverse populations. However, substantial inter-study variations hamper comparability. Standardized reporting practices would improve the quality, consistency and comprehension of study findings.
Topics: Humans; COVID-19; SARS-CoV-2; Post-Acute COVID-19 Syndrome; Acute Disease; Immunoglobulin G; Antibodies, Viral
PubMed: 38083997
DOI: 10.1111/eci.14149 -
Leukemia & Lymphoma 2023Relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) is a challenging disease with low rates of remission and survival in adult patients. Anti-CD19... (Meta-Analysis)
Meta-Analysis
Differences in efficacy and safety among CAR-Ts anti-CD19/CD22, anti-CD19, and anti-CD22, in adult patients with relapse/refractory B-cell acute lymphoblastic leukemia: a meta-analysis and systematic review.
Relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) is a challenging disease with low rates of remission and survival in adult patients. Anti-CD19 Chimeric Antigen Receptor T-cells (CAR-Ts) therapies have been approved for these patients. Dual-target CAR-Ts against CD19 and CD22 have recently been developed to improve the efficacy of the single-target therapy; however, extent of the improvement using this dual-target therapy has yet to be determined. We performed a meta-analysis of the outcome and safety of CAR-Ts, comparing anti-CD19 vs anti-CD22 vs dual-target anti-CD19/CD22 CAR-Ts, to elucidate the differences and limitations of these therapies in adult patients with R/R B-ALL. our results suggest that anti-CD19/CD22 CAR-Ts generate lower incidence of relapse and neurotoxicity, but similar results were obtained regarding complete remission, minimal residual disease, overall survival, and cytokine release syndrome compared with single-target anti-CD19 and anti-CD22 CAR-Ts.
Topics: Humans; Adult; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Lymphoma, B-Cell; Antigens, CD19; Acute Disease; Sialic Acid Binding Ig-like Lectin 2
PubMed: 37548560
DOI: 10.1080/10428194.2023.2243357 -
European Journal of Clinical... Feb 2024Calprotectin is a calcium-binding-S100-protein synthetized mainly in neutrophils which has been demonstrated to be an accurate biomarker of the presence of these cells.... (Review)
Review
BACKGROUND
Calprotectin is a calcium-binding-S100-protein synthetized mainly in neutrophils which has been demonstrated to be an accurate biomarker of the presence of these cells. Gut barrier dysfunction in patients with advanced chronic liver disease (ACLD), in addition to the lack of noninvasive tools for diagnosis and prognosis of cirrhosis decompensations, has raised interest in this biomarker.
AIMS
Our aim is to summarize the current evidence regarding the role of calprotectin in terms of its diagnostic and prognostic utility in ACLD.
METHODS
We performed a systematic search (PROSPERO registration no. CRD42023389069) of original articles published without any restrictions on the publication date until January 2023 providing information about calprotectin for the prognosis or diagnosis of ACLD and its decompensations in adult patients.
RESULTS
A total 227 articles were identified, and 26 observational studies finally met the inclusion criteria. In 14 studies, calprotectin was measured in ascitic fluid, all of which reported higher calprotectin values in spontaneous bacterial peritonitis, while cut-off points for its diagnosis were proposed in nine studies. Three studies reported higher faecal calprotectin levels in patients with hepatic encephalopathy and portal hypertension. Four studies evaluated faecal calprotectin and one plasma calprotectin as biomarkers for gut barrier integrity and bacterial translocation.
CONCLUSIONS
Calprotectin is emerging as a promising biomarker in ACLD, particularly for the management of bacterial infections and alcohol-related liver disease. Further research with better study designs should help to determine the feasibility of calprotectin measurement in routine clinical practice.
Topics: Adult; Humans; Biomarkers; Hypertension, Portal; Leukocyte L1 Antigen Complex; Liver Cirrhosis; Prognosis
PubMed: 37849372
DOI: 10.1111/eci.14111 -
Tropical Medicine and Infectious Disease Sep 2023The Duffy protein, a transmembrane molecule, functions as a receptor for various chemokines and facilitates attachment between the reticulocyte and the Duffy... (Review)
Review
The Duffy protein, a transmembrane molecule, functions as a receptor for various chemokines and facilitates attachment between the reticulocyte and the Duffy antigen-binding protein. Duffy expression correlates with the Duffy receptor gene for the chemokine, located on chromosome 1, and exhibits geographical variability worldwide. Traditionally, researchers have described the Duffy negative genotype as a protective factor against infection. However, recent studies suggest that this microorganism's evolution could potentially diminish this protective effect. Nevertheless, there is currently insufficient global data to demonstrate this phenomenon. This study aimed to evaluate the relationship between the Duffy genotype/phenotype and the prevalence of infection. The protocol for the systematic review was registered in PROSPERO as CRD42022353427 and involved reviewing published studies from 2012 to 2022. The Medline/PubMed, Web of Science, Scopus, and SciELO databases were consulted. Assessments of study quality were conducted using the STROBE and GRADE tools. A total of 34 studies were included, with Africa accounting for the majority of recorded studies. The results varied significantly regarding the relationship between the Duffy genotype/phenotype and invasion. Some studies predominantly featured the negative Duffy genotype yet reported no malaria cases. Other studies identified minor percentages of infections. Conversely, certain studies observed a higher prevalence (99%) of Duffy-negative individuals infected with In conclusion, this systematic review found that the homozygous Duffy genotype positive for the A allele (FY*A/*A) is associated with a higher incidence of infection. Furthermore, the negative Duffy genotype does not confer protection against vivax malaria.
PubMed: 37888591
DOI: 10.3390/tropicalmed8100463 -
Annals of Medicine Dec 2024Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an... (Meta-Analysis)
Meta-Analysis
Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis.
BACKGROUND
Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events. This study assessed the efficacy and safety of CAR T-cell therapy for r/r B-ALL.
METHODS
The literature search was performed on four databases. Efficacy parameters included minimal residual disease negative complete remission (MRD-CR) and relapse rate (RR). Safety parameters constituted cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
RESULTS
Anti-CD22 showed superior efficacy with the highest MRD-CR event rate and lowest RR, compared to anti-CD19. Combining CAR T-cell therapy with haploidentical stem cell transplantation improved RR. Safety-wise, bispecific anti-CD19/22 had the lowest CRS rate, and anti-CD22 showed the fewest ICANS. Analysis of the costimulatory receptors showed that adding CD28ζ to anti-CD19 CAR T-cell demonstrated superior efficacy in reducing relapses with favorable safety profiles.
CONCLUSION
Choosing a more efficacious and safer CAR T-cell treatment is crucial for improving overall survival in acute leukaemia. Beyond the promising anti-CD22 CAR T-cell, exploring costimulatory domains and new CD targets could enhance treatment effectiveness for r/r B-ALL.
Topics: Humans; Immunotherapy, Adoptive; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Antigens, CD19; Sialic Acid Binding Ig-like Lectin 2; Receptors, Chimeric Antigen; Child; Treatment Outcome; Neoplasm, Residual; Cytokine Release Syndrome; Recurrence; Neurotoxicity Syndromes
PubMed: 38738799
DOI: 10.1080/07853890.2024.2349796