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Journal of Personalized Medicine Feb 2024Chondrosarcomas rank as the second most common primary bone malignancy. Characterized by the production of a cartilaginous matrix, these tumors typically exhibit... (Review)
Review
BACKGROUND
Chondrosarcomas rank as the second most common primary bone malignancy. Characterized by the production of a cartilaginous matrix, these tumors typically exhibit resistance to both radiotherapy (RT) and chemotherapy (CT), resulting in overall poor outcomes: a high rate of mortality, especially among children and adolescents. Due to the considerable resistance to current conventional therapies such as surgery, CT, and RT, there is an urgent need to identify factors contributing to resistance and discover new strategies for optimal treatment. Over the past decade, researchers have delved into the dysregulation of genes associated with tumor development and therapy resistance to identify potential therapeutic targets for overcoming resistance. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including isocitrate dehydrogenase (IDH1/2) and COL2A1. Molecule-targeting agents and immunotherapies have demonstrated favorable antitumor activity in clinical studies involving patients with advanced chondrosarcomas. In this systematic review, we delineate the clinical features of chondrosarcoma and provide a summary of gene dysregulation and mutation associated with tumor development, as well as targeted therapies as a promising molecular approach. Finally, we analyze the probable role of the tumor microenvironment in chondrosarcoma drug resistance.
METHODS
A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 10 November 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chondrosarcomas", "target therapies", "immunotherapies", and "outcomes". The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of target therapies for the treatment of chondrosarcoma in human subjects.
RESULTS
Of the initial 279 articles identified, 40 articles were included in the article. The exclusion of 140 articles was due to reasons such as irrelevance, non-reporting of selected results, systematic literature review or meta-analysis, and lack of details on the method/results. Three tables highlighted clinical studies, preclinical studies, and ongoing clinical trials, encompassing 13, 7, and 20 studies, respectively. For the clinical study, a range of molecular targets, such as death receptors 4/5 (DR4 and DR5) (15%), platelet-derived growth factor receptor-alpha or -beta (PDGFR-α, PDGFR-β) (31%), were investigated. Adverse events were mainly constitutional symptoms emphasizing that to improve therapy tolerance, careful observation and tailored management are essential. Preclinical studies analyzed various molecular targets such as DR4/5 (28.6%) and COX-2 (28.6%). The prevalent indicator of antitumoral activity was the apoptotic rate of both a single agent (tumor necrosis factor-related apoptosis-inducing ligand: TRAIL) and double agents (TRAIL-DOX, TRAIL-MG132). Ongoing clinical trials, the majority in Phase II (53.9%), highlighted possible therapeutic strategies such as IDH1 inhibitors and PD-1/PD-L1 inhibitors (30.8%).
CONCLUSIONS
The present review offers a comprehensive analysis of targeted therapeutics for skull base chondrosarcomas, highlighting a complex landscape characterized by a range of treatment approaches and new opportunities for tailored interventions. The combination of results from molecular research and clinical trials emphasizes the necessity for specialized treatment strategies and the complexity of chondrosarcoma biology.
PubMed: 38541003
DOI: 10.3390/jpm14030261 -
Sports (Basel, Switzerland) Mar 2024Adenosine triphosphate (ATP) is an energy and signaling molecule. It is synthesized endogenously and can be taken as an oral supplement. This review aimed to identify... (Review)
Review
Adenosine triphosphate (ATP) is an energy and signaling molecule. It is synthesized endogenously and can be taken as an oral supplement. This review aimed to identify the effects of oral ATP supplementation on anaerobic exercise in healthy resistance-trained adults. A systematic review and meta-analysis were performed based on the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) criteria. The inclusion criteria were articles published from 2000 to 2022, with anaerobic variables (maximal strength, maximum repetitions, and maximum anaerobic power) measurable in healthy adults with experience in resistance training, only randomized placebo-controlled clinical trials (RCTs), and with the acute (a single dose 30 min to 24 h before the tests) and/or chronic (>1 day) oral supplementation of ATP. A total of five RCTs with 121 adult men were included. The oral ATP supplementation achieved significantly greater gains in maximal strength compared with the placebo (PL) (MD = 8.13 kg, 95%CI [3.36-12.90], < 0.001). Still, no differences were observed in the maximum number of repetitions or the maximum anaerobic power. Furthermore, 400 mg of ATP showed improvement in anaerobic exercise regardless of the duration of the supplementation protocol. In conclusion, supplementation with 400 mg of ATP doses can improve maximal muscle strength in resistance-trained men.
PubMed: 38535745
DOI: 10.3390/sports12030082 -
Marine Drugs Feb 2024Non-small-cell lung cancer (NSCLC), the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide, has been extensively investigated in the... (Review)
Review
Non-small-cell lung cancer (NSCLC), the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide, has been extensively investigated in the last decade in terms of developing new therapeutic options that increase patient survival. In this context, marine animals are a source of new, interesting bioactive molecules that have been applied to the treatment of different types of cancer. Many efforts have been made to search for new therapeutic strategies to improve the prognosis of lung cancer patients, including new bioactive compounds and cytotoxic drugs from marine sponges. Their antitumoral effect can be explained by several cellular and molecular mechanisms, such as modulation of the cell cycle or induction of apoptosis. Thus, this systematic review aims to summarize the bioactive compounds derived from marine sponges and the mechanisms by which they show antitumor effects against lung cancer, exploring their limitations and the challenges associated with their discovery. The search process was performed in three databases (PubMed, SCOPUS, and Web of Science), yielding a total of 105 articles identified in the last 10 years, and after a screening process, 33 articles were included in this systematic review. The results showed that these natural sponge-derived compounds are a valuable source of inspiration for the development of new drugs. However, more research in this field is needed for the translation of these novel compounds to the clinic.
Topics: Animals; Humans; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Biological Products; Apoptosis; Porifera
PubMed: 38535442
DOI: 10.3390/md22030101 -
The Journal of Allergy and Clinical... May 2024Access to the molecular culprits of allergic reactions allows for the leveraging of molecular allergology as a new precision medicine approach-one built on... (Review)
Review
Access to the molecular culprits of allergic reactions allows for the leveraging of molecular allergology as a new precision medicine approach-one built on interdisciplinary, basic, and clinical knowledge. Molecular allergology relies on the use of allergen molecules as tools for the diagnosis and management of allergic patients. It complements the conventional approach based on skin and allergen extract testing. Major applications of molecular allergology comprise accurate identification of the offending allergen thanks to discrimination between genuine sensitization and allergen cross-reactivity, evaluation of potential severity, patient-tailored choice of the adequate allergen immunotherapy, and prediction of its expected efficacy and safety. Allergen cross-reactivity, defined as the recognition of 2 or more allergen molecules by antibodies or T cells of the same specificity, frequently interferes with allergen extract testing. At the mechanistic level, allergen cross-reactivity depends on the allergen, the host's immune response, and the context of their interaction. The multiplicity of allergen molecules and families adds further difficulty. Understanding allergen cross-reactivity at the immunologic level and translating it into a daily tool for the management of allergic patients is further complicated by the ever-increasing number of characterized allergenic molecules, the lack of dedicated resources, and the need for a personalized, patient-centered approach. Conversely, knowledge sharing paves the way for improved clinical use, innovative diagnostic tools, and further interdisciplinary research. Here, we aimed to provide a comprehensive and unbiased state-of-the art systematic review on allergen cross-reactivity. To optimize learning, we enhanced the review with basic, translational, and clinical definitions, clinical vignettes, and an overview of online allergen databases.
PubMed: 38524786
DOI: 10.1016/j.jacig.2024.100230 -
World Journal of Gastroenterology Feb 2024Most patients with advanced pancreatic neuroendocrine tumors (pNETs) die due to tumor progression. Therefore, identifying new therapies with low toxicity and good... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Most patients with advanced pancreatic neuroendocrine tumors (pNETs) die due to tumor progression. Therefore, identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant. In this perspective, metformin is emerging as a molecule of interest. Retrospective studies have described metformin, a widely used agent for the treatment of patients with type 2 diabetes mellitus (T2DM), to be effective in modulating different tumor-related events, including cancer incidence, recurrence and survival by inhibiting mTOR phosphorylation. This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.
AIM
To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and post-treatment outcomes of pNET.
METHODS
A systematic review of the published literature was undertaken, focusing on the role of T2DM and metformin in insurgence and prognosis of pNET, measured through outcomes of tumor-free survival (TFS), overall survival and progression-free survival.
RESULTS
A total of 13 studies (5674 patients) were included in this review. Analysis of 809 pNET cases from five retrospective studies (low study heterogeneity with = 0%) confirms the correlation between T2DM and insurgence of pNET (OR = 2.13, 95%CI = 1.56-4.55; < 0.001). The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients (hazard ratio = 1.84, 95%CI = 0.78-2.90; < 0.001). The study heterogeneity was intermediate, with = 51%. A few studies limited the possibility of performing pooled analysis in the setting of metformin; therefore, results were heterogeneous, with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.
CONCLUSION
T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients. Unfortunately, a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Neuroendocrine Tumors; Retrospective Studies; Pancreatic Neoplasms; Neuroectodermal Tumors, Primitive
PubMed: 38515954
DOI: 10.3748/wjg.v30.i7.759 -
Saudi Journal of Biological Sciences May 2024Camels are highly suited for severe desert conditions and able to provide most of the natural products like urine, which has been used as alternative medicine to treat... (Review)
Review
Camels are highly suited for severe desert conditions and able to provide most of the natural products like urine, which has been used as alternative medicine to treat diverse infections and disorders. There is, however, a shortage and paucity of scientific reviews highlighting the antifungal, antibacterial and antiviral effects of camel urine. By better understanding its antimicrobial characteristics, our overarching aim is to provide an exhaustive overview of this valuable natural product by synthesizing and summarizing data on the efficacy of this biofluid and also describing the potential substances exhibiting antimicrobial properties. We searched three databases in order to point out relevant articles (Web of Science, Scopus and Google Scholar) until December 2022. Research articles of interest evaluating the antimicrobial effects of camel urine were selected. Overall, camel urine furnished promising antibacterial activities against gram-positive bacteria, namely (30 mm), (22 mm), (25 mm) and (21 mm), as well as gram-negative bacteria, especially and spp., without forgetting its efficiency on as well. The excretion also showed its potency against H1N1 virus, vesicular stomatitis virus and middle east respiratory syndrome coronavirus. Similarly, the camel urine featured strong antifungal activity against and dermatophytes with a minimal inhibitory concentration of 0.625 μg/ml against , 2.5 μg/ml against and 1.25 μg/ml against and . This comprehensive review will be valuable for researchers interested in investigating the potential of camel urine in the development of novel broad-spectrum key molecules targeting a wide range of drug-resistant pathogenic microorganisms.
PubMed: 38495380
DOI: 10.1016/j.sjbs.2024.103966 -
International Journal of Antimicrobial... May 2024Intracellular human pathogens are the deadliest infectious diseases and are difficult to treat effectively due to their protection inside the host cell and the... (Review)
Review
Intracellular human pathogens are the deadliest infectious diseases and are difficult to treat effectively due to their protection inside the host cell and the development of antimicrobial resistance (AMR). An emerging approach to combat these intracellular pathogens is host-directed therapies (HDT), which harness the innate immunity of host cells. HDT rely on small molecules to promote host protection mechanisms that ultimately lead to pathogen clearance. These therapies are hypothesized to: (1) possess indirect yet broad, cross-species antimicrobial activity, (2) effectively target drug-resistant pathogens, (3) carry a reduced susceptibility to the development of AMR and (4) have synergistic action with conventional antimicrobials. As the field of HDT expands, this systematic review was conducted to collect a compendium of HDT and their characteristics, such as the host mechanisms affected, the pathogen inhibited, the concentrations investigated and the magnitude of pathogen inhibition. The evidential support for the main four HDT hypotheses was assessed and concluded that HDT demonstrate robust cross-species activity, are active against AMR pathogens, clinical isolates and laboratory-adapted pathogens. However, limited information exists to support the notion that HDT are synergistic with canonical antimicrobials and are less predisposed to AMR development.
Topics: Humans; Immunity, Innate; Anti-Infective Agents; Drug Synergism; Bacteria; Anti-Bacterial Agents; Host-Pathogen Interactions
PubMed: 38490573
DOI: 10.1016/j.ijantimicag.2024.107138 -
Cureus Mar 2024This is the first systematic review and meta-analysis that aims to address the scarcity of research on the use of biological therapy in primary sclerosing... (Review)
Review
This is the first systematic review and meta-analysis that aims to address the scarcity of research on the use of biological therapy in primary sclerosing cholangitis-inflammatory bowel disease (PSC-IBD) and the historical inadequacy of therapeutic options. Its purpose is to investigate this matter comprehensively and furnish guidance for clinical practice. Utilizing Embase, PubMed, Medline, and clinicaltrials.gov studies investigating the roles of biologics and antibiotics in PSC-IBD were identified. The systematic literature review encompassed articles published from inception through September 2023. Two independent reviewers assessed the articles, and methodological quality was gauged using Review Manager 5.4.2. Nine studies were included in the systematic review and meta-analysis. However, only four met the criteria for inclusion in the meta-analysis due to variability and availability of data; the remaining studies underwent descriptive analysis. Notably, infliximab, adalimumab, vedolizumab, and tofacitinib showed ineffectiveness in reducing cholestatic markers. This review underscores the limited impact of biological and small-molecule therapies on disease progression in PSC-IBD patients, signifying the need for further exploration and development of treatment modalities in this domain.
PubMed: 38487649
DOI: 10.7759/cureus.56182 -
Frontiers in Cell and Developmental... 2024Cell death is ubiquitous during development and throughout life and is a genetically determined active and ordered process that plays a crucial role in regulating... (Review)
Review
Cell death is ubiquitous during development and throughout life and is a genetically determined active and ordered process that plays a crucial role in regulating homeostasis. Cell death includes regulated cell death and non-programmed cell death, and the common types of regulatory cell death are necrosis, apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis. Apoptosis, Necrosis and necroptosis are more common than autophagy, ferroptosis and pyroptosis among cell death. Non-coding RNAs are regulatory RNA molecules that do not encode proteins and include mainly microRNAs, long non-coding RNAs, and circular RNAs. Non-coding RNAs can act as oncogenes and tumor suppressor genes, with significant effects on tumor occurrence and development, and they can also regulate tumor cell autophagy, ferroptosis, and pyroptosis at the transcriptional or post-transcriptional level. This paper reviews the recent research progress on the effects of the non-coding RNAs involved in autophagy, ferroptosis, and pyroptosis on tumorigenesis, tumor development, and treatment, and looks forward to the future direction of this field, which will help to elucidate the molecular mechanisms of tumorigenesis and tumor development, as well as provide a new vision for the treatment of tumors.
PubMed: 38481525
DOI: 10.3389/fcell.2024.1284934 -
International Journal of Molecular... Feb 2024Juvenile Idiopathic Arthritis (JIA) is currently the most common chronic rheumatic disease in children. It is known to have no single identity, but a variety of... (Review)
Review
UNLABELLED
Juvenile Idiopathic Arthritis (JIA) is currently the most common chronic rheumatic disease in children. It is known to have no single identity, but a variety of diagnoses. Under-diagnosis is a barrier to early treatment and reduced complications of the disease. Other immune-mediated diseases may coexist in the same patient, making research in this area relevant. The main objective was to analyse whether links could be established between the molecular basis of JIA and other immune-mediated diseases. Early diagnosis may benefit patients with JIA, which in most cases goes undetected, leading to under-diagnosis, which can have a negative impact on children affected by the disease as they grow up.
METHODS
We performed a PRISMA systematic review focusing on immune molecules present in different autoimmune diseases.
RESULTS
A total of 13 papers from different countries dealing with the molecular basis of JIA and other immune diseases were evaluated and reviewed.
CONCLUSIONS
Most of the autoimmune diseases analysed responded to the same group of drugs. Unfortunately, the reason for the under-diagnosis of these diseases remains unknown, as no evidence has been found to correlate the immunomolecular basis with the under-diagnosis of these immune-mediated diseases. The lack of information in this area means that further research is needed in order to provide a sound basis for preventing the development of immune-mediated diseases, especially in children, and to improve their quality of life through early diagnosis and treatment.
Topics: Child; Humans; Arthritis, Juvenile; Quality of Life; Rheumatic Diseases
PubMed: 38474052
DOI: 10.3390/ijms25052803