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Frontiers in Immunology 2024Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing...
Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing promising results for numerous cancer patients. However, significant advancements are required before CAR-T therapies become readily available as off-the-shelf treatments, particularly for solid tumors and lymphomas. In this review, we have systematically analyzed the combination therapy involving engineered CAR-T cells and anti PD-1 agents. This approach aims at overcoming the limitations of current treatments and offers potential advantages such as enhanced tumor inhibition, alleviated T-cell exhaustion, heightened T-cell activation, and minimized toxicity. The integration of CAR-T therapy, which targets tumor-associated antigens, with PD-1 blockade augments T-cell function and mitigates immune suppression within the tumor microenvironment. To assess the impact of combination therapy on various tumors and lymphomas, we categorized them based on six major tumor-associated antigens: mesothelin, disialoganglioside GD-2, CD-19, CD-22, CD-133, and CD-30, which are present in different tumor types. We evaluated the efficacy, complete and partial responses, and progression-free survival in both pre-clinical and clinical models. Additionally, we discussed potential implications, including the feasibility of combination immunotherapies, emphasizing the importance of ongoing research to optimize treatment strategies and improve outcomes for cancer patients. Overall, we believe combining CAR-T therapy with PD-1 blockade holds promise for the next generation of cancer immunotherapy.
Topics: Humans; Programmed Cell Death 1 Receptor; Immunotherapy, Adoptive; Lymphoma; Immune Checkpoint Inhibitors; Receptors, Chimeric Antigen; Animals; Neoplasms; Combined Modality Therapy; Tumor Microenvironment; Antigens, Neoplasm; T-Lymphocytes
PubMed: 38799440
DOI: 10.3389/fimmu.2024.1389971 -
BMJ Mental Health May 2024Does neurodegenerative disease underlie the increased rate of dementia observed in older people with schizophrenia? Several studies have reported a higher prevalence of... (Meta-Analysis)
Meta-Analysis Review
QUESTION
Does neurodegenerative disease underlie the increased rate of dementia observed in older people with schizophrenia? Several studies have reported a higher prevalence of dementia in people with schizophrenia compared with the general population. This may reflect a higher risk of developing neurodegenerative diseases such as vascular dementia or Alzheimer's disease (AD). Alternatively, this may reflect non-pathological, age-related cognitive decline in a population with low cognitive reserve.
STUDY SELECTION AND ANALYSIS
We reviewed papers that compared postmortem findings, hippocampal MRI volume or cerebrospinal fluid (CSF) markers of AD, between patients with schizophrenia with evidence of cognitive impairment (age ≥45 years) with controls. We subsequently performed a meta-analysis of postmortem studies that compared amyloid-β plaques (APs) or neurofibrillary tangles (NFTs) in cognitively impaired patients with schizophrenia to normal controls or an AD group.
FINDINGS
No studies found a significant increase of APs or NFTs in cognitively impaired patients with schizophrenia compared with controls. All postmortem studies that compared APs or NFTs in patients with schizophrenia to an AD group found significantly more APs or NFTs in AD. No studies found a significant differences in CSF total tau or phosphorylated tau between patients with schizophrenia and controls. The two studies which compared CSF Aβ42 between patients with schizophrenia and controls found significantly decreased CSF Aβ42 in schizophrenia compared with controls. Hippocampal volume findings were mixed.
CONCLUSIONS
Studies have not found higher rates of AD-related pathology in cognitively impaired individuals with schizophrenia compared with controls. Higher rates of dementia identified in population studies may reflect a lack of specificity in clinical diagnostic tools used to diagnose dementia.
Topics: Humans; Schizophrenia; Biomarkers; Neurodegenerative Diseases; Alzheimer Disease; Amyloid beta-Peptides; Neurofibrillary Tangles; Plaque, Amyloid
PubMed: 38796179
DOI: 10.1136/bmjment-2024-301017 -
Biomedicine & Pharmacotherapy =... Jul 2024Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising... (Review)
Review
Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising human life and health. Activating transcription factor 4 (ATF4) participates in the regulation of multiple pathophysiological processes, including CNS disorders. Considering the widespread involvement of ATF4 in the pathological process of CNS disorders, the targeted regulation of ATF4 by plant-derived bioactive compounds (PDBCs) may become a viable strategy for the treatment of CNS disorders. However, the regulatory relationship between PDBCs and ATF4 remains incompletely understood. Here, we aimed to comprehensively review the studies on PDBCs targeting ATF4 to ameliorate CNS disorders, thereby offering novel directions and insights for the treatment of CNS disorders. A computerized search was conducted on PubMed, Embase, Web of Science, and Google Scholar databases to identify preclinical experiments related to PDBCs targeting ATF4 for the treatment of CNS disorders. The search timeframe was from the inception of the databases to December 2023. Two assessors conducted searches using the keywords "ATF4," "Central Nervous System," "Neurological," "Alzheimer's disease," "Parkinson's Disease," "Stroke," "Spinal Cord Injury," "Glioblastoma," "Traumatic Brain Injury," and "Spinal Cord Injury." Overall, 31 studies were included, encompassing assessments of 27 PDBCs. Combining results from in vivo and in vitro studies, we observed that these PDBCs, via ATF4 modulation, prevent the deposition of amyloid-like fibers such as Aβ, tau, and α-synuclein. They regulate ERS, reduce the release of inflammatory factors, restore mitochondrial membrane integrity to prevent oxidative stress, regulate synaptic plasticity, modulate autophagy, and engage anti-apoptotic mechanisms. Consequently, they exert neuroprotective effects in CNS disorders. Numerous PDBCs targeting ATF4 have shown potential in facilitating the restoration of CNS functionality, thereby presenting expansive prospects for the treatment of such disorders. However, future endeavors necessitate high-quality, large-scale, and comprehensive preclinical and clinical studies to further validate this therapeutic potential.
Topics: Activating Transcription Factor 4; Humans; Central Nervous System Diseases; Animals; Phytochemicals; Neuroprotective Agents
PubMed: 38795641
DOI: 10.1016/j.biopha.2024.116811 -
Viruses Apr 2024This systematic review investigates the immunosuppressive environment in HBV-associated hepatocellular carcinoma (HCC), characterized by dysfunctional and exhausted... (Review)
Review
This systematic review investigates the immunosuppressive environment in HBV-associated hepatocellular carcinoma (HCC), characterized by dysfunctional and exhausted HBV-specific T cells alongside an increased infiltration of HBV-specific CD4+ T cells, particularly regulatory T cells (Tregs). Heightened expression of checkpoint inhibitors, notably PD-1, is linked with disease progression and recurrence, indicating its potential as both a prognostic indicator and a target for immunotherapy. Nevertheless, using PD-1 inhibitors has shown limited effectiveness. In a future perspective, understanding the intricate interplay between innate and adaptive immune responses holds promise for pinpointing predictive biomarkers and crafting novel treatment approaches for HBV-associated HCC.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Hepatitis B virus; Adaptive Immunity; T-Lymphocytes, Regulatory; Programmed Cell Death 1 Receptor; Immune Checkpoint Inhibitors; Hepatitis B; Hepatitis B, Chronic; CD4-Positive T-Lymphocytes; T-Lymphocytes; Immunotherapy
PubMed: 38793588
DOI: 10.3390/v16050707 -
Journal of Personalized Medicine Apr 2024Pancreatic cancer is one of the most aggressive, heterogeneous, and fatal types of human cancer; therefore, more effective therapeutic drugs are urgently needed. Human... (Review)
Review
Pancreatic cancer is one of the most aggressive, heterogeneous, and fatal types of human cancer; therefore, more effective therapeutic drugs are urgently needed. Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been identified as a cornerstone in this pathology. The aim of this review is to identify HER2 membrane overexpression in relation to pancreatic cancer pathways that can be used in order to develop a targeted therapy. After searching the keywords, 174 articles were found during a time span of 10 years, between 2013 and 2023, but only twelve scientific papers were qualified for this investigation. The new era of biomolecular research found a significant relationship between HER2 overexpression and pancreatic cancer cells in 25-30% of cases. The variables are dependent on tumor-derived cells, with differences in receptor overexpression between PDAC (pancreatic ductal adenocarcinoma), BTC (biliary tract cancer), ampullary carcinoma, and PNETs (pancreatic neuroendocrine tumors). HER2 overexpression is frequently encountered in human pancreatic carcinoma cell lines, and the ERBB family is one of the targets in the near future of therapy, with good results in phase I, II, and III studies evaluating downregulation and tumor downstaging, respectively.
PubMed: 38793045
DOI: 10.3390/jpm14050463 -
International Journal of Molecular... May 2024Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as... (Meta-Analysis)
Meta-Analysis Review
Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as well as on inflammatory cells (e.g., tumor-infiltrating T cells, TILs) in the tumor microenvironment. Expressional changes of chemokines and their receptors in solid cancers are common and well known, especially in affecting colorectal cancer patient outcomes. Therefore, the aim of this current systematic review and meta-analysis was to classify chemokines as a prognostic biomarker in colorectal cancer patients. A systematic literature search was conducted in PubMed, CENTRAL and Web of Science. Information on the chemokine expression of 25 chemokines in colorectal cancer tissue and survival data of the patients were investigated. The hazard ratio of overall survival and disease-free survival with chemokine expression was examined. The risk of bias was analyzed using Quality in Prognosis Studies. Random effects meta-analysis was performed to determine the impact on overall respectively disease survival. For this purpose, the pooled hazard ratios (HR) and their 95% confidence intervals (CI) were used for calculation. Twenty-five chemokines were included, and the search revealed 5556 publications. A total of thirty-one publications were included in this systematic review and meta-analysis. Overexpression of chemokine receptor CXCR4 was associated with both a significantly reduced overall survival (HR = 2.70, 95%-CI: 1.57 to 4.66, = 0.0003) as well as disease-free survival (HR = 2.68, 95%-CI: 1.41 to 5.08, = 0.0026). All other chemokines showed either heterogeneous results or few studies were available. The overall risk of bias for CXCR4 was rated low. At the current level of evidence, this study demonstrates that CXCR4 overexpression in patients with colorectal cancer is associated with a significantly diminished overall as well as disease-free survival. Summed up, this systematic review and meta-analysis reveals CXCR4 as a promising prognostic biomarker. Nevertheless, more evidence is needed to evaluate CXCR4 and its antagonists serving as new therapeutic targets.
Topics: Humans; Colorectal Neoplasms; Prognosis; Biomarkers, Tumor; Chemokines; Receptors, CXCR4; Disease-Free Survival
PubMed: 38791414
DOI: 10.3390/ijms25105374 -
International Journal of Molecular... May 2024Numerous challenges remain within conventional cell-based therapy despite the growing trend of stem cells used to treat various life-debilitating diseases. These... (Review)
Review
Numerous challenges remain within conventional cell-based therapy despite the growing trend of stem cells used to treat various life-debilitating diseases. These limitations include batch-to-batch heterogeneity, induced alloreactivity, cell survival and integration, poor scalability, and high cost of treatment, thus hindering successful translation from lab to bedside. However, recent pioneering technology has enabled the isolation and enrichment of small extracellular vesicles (EVs), canonically known as exosomes. EVs are described as a membrane-enclosed cargo of functional biomolecules not limited to lipids, nucleic acid, and proteins. Interestingly, studies have correlated the biological role of MSC-EVs to the paracrine activity of MSCs. This key evidence has led to rigorous studies on MSC-EVs as an acellular alternative. Using EVs as a therapy was proposed as a model leading to improvements through increased safety; enhanced bioavailability due to size and permeability; reduced heterogeneity by selective and quantifiable properties; and prolonged shelf-life via long-term freezing or lyophilization. Yet, the identity and potency of EVs are still relatively unknown due to various methods of preparation and to qualify the final product. This is reflected by the absence of regulatory strategies overseeing manufacturing, quality control, clinical implementation, and product registration. In this review, the authors review the various production processes and the proteomic profile of MSC-EVs.
Topics: Humans; Mesenchymal Stem Cells; Extracellular Vesicles; Proteomics; Umbilical Cord; Exosomes; Proteome
PubMed: 38791378
DOI: 10.3390/ijms25105340 -
International Journal of Molecular... May 2024Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Given its prevalence, reliable biomarkers for early diagnosis are required.... (Meta-Analysis)
Meta-Analysis Review
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Given its prevalence, reliable biomarkers for early diagnosis are required. Exosomal proteins within extracellular nanovesicles are promising candidates for diagnostic, screening, prognostic, and disease monitoring purposes in neurological diseases such as PD. This review aims to evaluate the potential of extracellular vesicle proteins or miRNAs as biomarkers for PD. A comprehensive literature search until January 2024 was conducted across multiple databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, to identify relevant studies reporting exosome biomarkers in blood samples from PD patients. Out of 417 articles screened, 47 studies were selected for analysis. Among exosomal protein biomarkers, α-synuclein, tau, Amyloid β 1-42, and C-X-C motif chemokine ligand 12 (CXCL12) were identified as significant markers for PD. Concerning miRNA biomarkers, miRNA-24, miR-23b-3p, miR-195-3p, miR-29c, and mir-331-5p are promising across studies. α-synuclein exhibited increased levels in PD patients compared to control groups in twenty-one studies, while a decrease was observed in three studies. Our meta-analysis revealed a significant difference in total exosomal α-synuclein levels between PD patients and healthy controls (standardized mean difference [SMD] = 1.369, 95% confidence interval [CI] = 0.893 to 1.846, < 0.001), although these results are limited by data availability. Furthermore, α-synuclein levels significantly differ between PD patients and healthy controls (SMD = 1.471, 95% CI = 0.941 to 2.002, < 0.001). In conclusion, certain exosomal proteins and multiple miRNAs could serve as potential biomarkers for diagnosis, prognosis prediction, and assessment of disease progression in PD.
Topics: Humans; Parkinson Disease; Exosomes; Biomarkers; MicroRNAs; alpha-Synuclein; Amyloid beta-Peptides
PubMed: 38791346
DOI: 10.3390/ijms25105307 -
Genes May 2024This systematic review and meta-analysis aimed to verify the association between the genetic variants of adenosine triphosphate (ATP)-binding cassette subfamily B member... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis aimed to verify the association between the genetic variants of adenosine triphosphate (ATP)-binding cassette subfamily B member 1 () and ATP-binding cassette subfamily G member 2 () genes and the presence and severity of gefitinib-associated adverse reactions. We systematically searched PubMed, Virtual Health Library/Bireme, Scopus, Embase, and Web of Science databases for relevant studies published up to February 2024. In total, five studies were included in the review. Additionally, eight genetic variants related to (rs1045642, rs1128503, rs2032582, and rs1025836) and (rs2231142, rs2231137, rs2622604, and 15622C>T) genes were analyzed. Meta-analysis showed a significant association between the gene rs1045642 TT genotype and presence of diarrhea (OR = 5.41, 95% CI: 1.38-21.14, I = 0%), the gene rs1128503 TT genotype and CT + TT group and the presence of skin rash (OR = 4.37, 95% CI: 1.51-12.61, I = 0% and OR = 6.99, 95%CI: 1.61-30.30, I= 0%, respectively), and the gene rs2231142 CC genotype and presence of diarrhea (OR = 3.87, 95% CI: 1.53-9.84, I = 39%). No or genes were positively associated with the severity of adverse reactions associated with gefitinib. In conclusion, this study showed that and variants are likely to exhibit clinical implications in predicting the presence of adverse reactions to gefitinib.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 2; Humans; ATP Binding Cassette Transporter, Subfamily B; Gefitinib; Neoplasm Proteins; Polymorphism, Single Nucleotide; Antineoplastic Agents; Drug-Related Side Effects and Adverse Reactions; Genotype
PubMed: 38790220
DOI: 10.3390/genes15050591 -
Renal Failure Dec 2024This study aims to investigate the incidence and prognosis of malignancy in individuals with thrombospondin type-1 domain-containing 7A (THSD7A)-associated membranous...
BACKGROUND
This study aims to investigate the incidence and prognosis of malignancy in individuals with thrombospondin type-1 domain-containing 7A (THSD7A)-associated membranous nephropathy (MN).
METHODS
First, we performed a systematic literature review of prevalence of malignancy in THSD7A-associated MN. Then, we conducted a retrospective analysis of 454 patients diagnosed with MN through renal biopsy at our hospital between January 2016 and December 2020. We assessed the presence of serum anti-THSD7A antibodies and performed immunohistochemical staining of renal tissue for THSD7A. Subsequently, we followed patients with THSD7A-associated MN for a minimum of 3-5 years, collecting their clinical, pathological characteristics, and prognosis. Additionally, we conducted a literature review on patients with THSD7A-associated MN in conjunction with malignancy.
RESULTS
We identified a total of nine articles containing comprehensive data on THSD7A-associated MN and malignancy. Among 235 patients with THSD7A-positive MN, 36 individuals had concurrent malignancies, resulting in a malignancy prevalence of 13.3% (95% CI: 8.9-17.7%). In our center, we followed up with 15 patients diagnosed with THSD7A-associated MN and observed three cases of concomitant tumors: two cases of lung adenocarcinoma and one case of small cell lung cancer with multiple metastases. The prevalence of malignancy in our cohort was 20%. Notably, we detected positive THSD7A staining in both renal and lung cancer tissues in one patient with small cell lung cancer.
CONCLUSIONS
Patients with THSD7A-associated MN should undergo vigilant follow-up assessments, with a particular focus on actively seeking potential tumorigenic lesions to prevent misdiagnosis or oversight.
Topics: Humans; Glomerulonephritis, Membranous; Prognosis; Thrombospondins; Prevalence; Retrospective Studies; Male; Middle Aged; Female; Adult; Neoplasms; Aged; Kidney
PubMed: 38785304
DOI: 10.1080/0886022X.2024.2355353