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Future Oncology (London, England) Jun 2024A consensus regarding subsequent therapeutic strategies for patients with platinum- and poly (ADP-ribose) polymerase inhibitor (PARPi)-resistant ovarian cancer is...
A consensus regarding subsequent therapeutic strategies for patients with platinum- and poly (ADP-ribose) polymerase inhibitor (PARPi)-resistant ovarian cancer is lacking. These patients typically receive non-platinum-based chemotherapy; however, survival outcomes remain poor. Compared with chemotherapy alone, combination therapy with novel target agents can provide additional benefits to these patients. Oregovomab, an investigational murine monoclonal antibody against CA-125, has shown promising efficacy in a phase II study in patients with recurrent ovarian cancer. Herein, we described the rationale and design of OPERA/KGOG 3065/APGOT-OV6, a multicenter, investigator-initiated, two-cohort, single-arm phase II trial, aimed at examining the efficacy of oregovomab plus non-platinum-based chemotherapy in patients with PARPi/platinum-resistant ovarian cancer. The primary end point was the objective response rate, according to RECIST 1.1. NCT05407584 (ClinicalTrials.gov).
PubMed: 38940373
DOI: 10.1080/14796694.2024.2357533 -
Disease Models & Mechanisms Jun 2024Interpreting the wealth of rare genetic variants discovered in population-scale sequencing efforts and deciphering their associations with human health and disease... (Review)
Review
Interpreting the wealth of rare genetic variants discovered in population-scale sequencing efforts and deciphering their associations with human health and disease present a critical challenge due to the lack of sufficient clinical case reports. One promising avenue to overcome this problem is deep mutational scanning (DMS), a method of introducing and evaluating large-scale genetic variants in model cell lines. DMS allows unbiased investigation of variants, including those that are not found in clinical reports, thus improving rare disease diagnostics. Currently, the main obstacle limiting the full potential of DMS is the availability of functional assays that are specific to disease mechanisms. Thus, we explore high-throughput functional methodologies suitable to examine broad disease mechanisms. We specifically focus on methods that do not require robotics or automation but instead use well-designed molecular tools to transform biological mechanisms into easily detectable signals, such as cell survival rate, fluorescence or drug resistance. Here, we aim to bridge the gap between disease-relevant assays and their integration into the DMS framework.
Topics: Humans; High-Throughput Screening Assays; Disease; Mutation; Genetic Variation; Animals
PubMed: 38940340
DOI: 10.1242/dmm.050573 -
Journal of Global Health Jun 2024Considering the large population of bronchiectasis and chronic obstructive pulmonary disease (COPD) patients in China, we aimed to conduct a thorough analysis that...
Analysis of clinical characteristics, prognosis and influencing factors in patients with bronchiectasis-chronic obstructive pulmonary disease overlap syndrome: A prospective study for more than five years.
BACKGROUND
Considering the large population of bronchiectasis and chronic obstructive pulmonary disease (COPD) patients in China, we aimed to conduct a thorough analysis that investigates the clinical characteristics and prognosis of bronchiectasis-COPD overlap syndrome (BCOS). Further, we aimed to explore factors associated with acute exacerbation and death in BCOS, which may be of value in its early diagnosis and intervention.
METHODS
We recruited inpatients with COPD from the second Xiangya Hospital of Central South University in China in August 2016, with follow-up until March 2022. Patients in the BCOS group had to meet the criteria for diagnosing bronchiectasis. We used self-completion questionnaires, clinical records, and self-reported data as primary data collection methods. We used Kaplan-Meier survival analyses and Cox proportional hazard models to assess the risk of severe acute exacerbation and death for BCOS during the follow-up period.
RESULTS
A total of 875 patients were included and followed up. Patients in the BCOS group had more females, fewer smokers, lower discharge COPD assessment test (CAT) scores, lower forced vital capacity (FVC), a higher likelihood of co-occurring active tuberculosis, higher levels of eosinophils and inflammatory markers, and a higher rate of positive sputum cultures for Pseudomonas aeruginosa than patients in the COPD-only group. Patients in the acute exacerbation group (AE+) were found to have lower body mass index (BMI), more frequent acute exacerbations, higher modified Medical Research Council (mMRC) dyspnoea grade on admission, higher inflammatory markers, lower FVC, higher rates of using inhaled bronchodilators, and higher rates of both positive and Pseudomonas aeruginosa positive sputum cultures. Patients in the 'death' group were older, had a lower BMI, had spent longer time in the hospital, had higher mMRC dyspnoea grade and CAT scores upon admission and discharge, had higher levels of inflammatory markers, lower rates of using inhaled bronchodilators, were more likely to have a combination of pulmonary heart disease and obsolete pulmonary tuberculosis, as well as a higher rate of fungus-positive sputum cultures. Both erythrocyte sedimentation rate at baseline and Pseudomonas aeruginosa culture positivity were confirmed as independent predictors of severe acute exacerbation in multivariate analysis during the years of follow-up. Fungus culture positivity baseline blood urea nitrogen, baseline lymphocyte count, comorbidities with obsolete pulmonary tuberculosis and comorbidities with pulmonary heart disease were verified as independent predictors of death in multivariate analysis during the years of follow-up. Kaplan-Meier curves under survival analysis demonstrated no statistically significant difference in mortality between the COPD and the BCOS groups at the full one, two, and three years of follow-up.
CONCLUSIONS
Patients with BCOS present with reduced lung function, increased susceptibility to different complications, elevated blood eosinophils and inflammatory markers, and elevated rates of positive Pseudomonas aeruginosa cultures. These distinctive markers are linked to a greater risk of severe acute exacerbations and mortality.
Topics: Humans; Female; Pulmonary Disease, Chronic Obstructive; Male; Bronchiectasis; Middle Aged; Prospective Studies; Aged; Prognosis; China; Risk Factors; Syndrome; Disease Progression
PubMed: 38940273
DOI: 10.7189/jogh.14.04129 -
Polski Przeglad Chirurgiczny Feb 2024<b><br>Introduction:</b> Colorectal cancer (CRC) was the third most common cancer and the second cause of cancer deaths worldwide in 2020. Its... (Comparative Study)
Comparative Study
<b><br>Introduction:</b> Colorectal cancer (CRC) was the third most common cancer and the second cause of cancer deaths worldwide in 2020. Its incidence has increased dramatically in people under 50 years of age (early-onset colorectal cancer; EOCRC).</br> <b><br>Aim:</b> The aim of this study was to compare two age groups of patients with colorectal cancer in terms of stage, prognostic factors, survival and incidence of recurrence.</br> <b><br>Materials and methods:</b> The study group consisted of 588 patients operated on between 1995 and 2005 at the University Hospital in Krakow in the Clinical Department of General, Oncological and Gastroenterological Surgery. A method of retrospective documentation analysis was used. Patients were divided into two age groups: up to forty years of age and between 45 and 65 years of age.</br> <b><br>Results:</b> Up to 40 years of age, stage IV colorectal cancer was diagnosed in 33.3% of patients, while between 45 and 65 years of age, it was diagnosed in 26.1%. Five-year survival differed according to tumour stage. In the two groups analysed, there was a significant difference between the survival curves (P = 0.00000). Also, comparing recurrence times in the paired group excluding cancer-independent deaths revealed a statistically significant difference between the groups (P = 0.006).</br> <b><br>Discussion:</b> The incidence of colorectal cancer has increased worldwide in young people under 50 years of age, and it is therefore recommended that the research presented here be studied, and that prognostic factors be analysed and multicentre prophylactic studies combined with health education of those at risk be encouraged. Cancer occurring in younger patients is characterized by advanced stage at diagnosis and five-year survival is lower and has a poorer prognosis. The availability is very important of early diagnosis to detect pre-cancerous and considered pre-cancerous conditions is important. This involves detecting lesions at a lower stage of the disease.</br> <b><br>Conclusions:</b> The availability of early diagnosis to detect precancerous and considered pre-cancerous conditions is very important. This involves detecting lesions at a lower stage of the disease. Diagnosing colorectal cancer at an early stage and treating the pre-cancerous lesions will improve treatment outcomes, resulting in fewer metastases and longer survival and recurrence times.</br>.
Topics: Humans; Female; Male; Colorectal Neoplasms; Adult; Middle Aged; Incidence; Poland; Retrospective Studies; Aged; Neoplasm Staging; Treatment Outcome; Neoplasm Recurrence, Local; Prognosis; Survival Rate; Age Factors; Young Adult
PubMed: 38940247
DOI: 10.5604/01.3001.0054.2671 -
Annals of Agricultural and... Jun 2024Ultraviolet light in the UV-C band is known as germicidal radiation and was widely used for both sterilization of the equipment and creation of a sterile environment....
INTRODUCTION AND OBJECTIVE
Ultraviolet light in the UV-C band is known as germicidal radiation and was widely used for both sterilization of the equipment and creation of a sterile environment. The aim of the study is to assess the effectiveness of inactivation of microorganisms deposited on surfaces with various textures by UV-C radiation disinfection devices.
MATERIAL AND METHODS
Five microorganisms (3 bacteria, virus, and fungus) deposited on metal, plastic, and glass surfaces with smooth and rough textures were irradiated with UV-C light emitted by low-pressure mercury lamp and ultraviolet emitting diodes (LEDs), from a distance of 0.5 m, 1 m, and 1.5 m to check their survivability after 20-minute exposure.
RESULTS AND CONCLUSIONS
Both tested UV-C sources were effective in inactivation of microorganisms; however, LED emitter was more efficient in this respect than the mercury lamp. The survival rate of microorganisms depended on the UV-C dose, conditioned by the distance from UV-C source being the highest at 0.5 m and the lowest at 1.5 m. For the tested microorganisms, the highest survival rate after UV-C irradiation was usually visible on glass and plastic surfaces. This observation should be considered in all environments where the type of material (from which the elements of technical equipment are manufactured and may be contaminated by specific activities) is important for maintaining the proper level of hygiene and avoiding the unwanted and uncontrolled spread of microbiological pollution.
Topics: Ultraviolet Rays; Disinfection; Fungi; Bacteria; Viruses; Surface Properties; Microbial Viability; Plastics; Glass
PubMed: 38940114
DOI: 10.26444/aaem/189695 -
Frontiers in Bioscience (Landmark... Jun 2024The incidence rate of oropharyngeal squamous cell carcinoma (OPSCC) worldwide is alarming. In the clinical community, there is a pressing necessity to comprehend the...
BACKGROUND
The incidence rate of oropharyngeal squamous cell carcinoma (OPSCC) worldwide is alarming. In the clinical community, there is a pressing necessity to comprehend the etiology of the OPSCC to facilitate the administration of effective treatments.
METHODS
This study confers an integrative genomics approach for identifying key oncogenic drivers involved in the OPSCC pathogenesis. The dataset contains RNA-Sequencing (RNA-Seq) samples of 46 Human papillomavirus-positive head and neck squamous cell carcinoma and 25 normal Uvulopalatopharyngoplasty cases. The differential marker selection is performed between the groups with a log2FoldChange (FC) score of 2, adjusted -value < 0.01, and screened 714 genes. The Particle Swarm Optimization (PSO) algorithm selects the candidate gene subset, reducing the size to 73. The state-of-the-art machine learning algorithms are trained with the differentially expressed genes and candidate subsets of PSO.
RESULTS
The analysis of predictive models using Shapley Additive exPlanations revealed that seven genes significantly contribute to the model's performance. These include , , and , which predominantly influence differentiating between sample groups. They were followed in importance by , , , and . The Random Forest and Bayes Net algorithms also achieved perfect validation scores when using PSO features. Furthermore, gene set enrichment analysis, protein-protein interactions, and disease ontology mining revealed a significant association between these genes and the target condition. As indicated by Shapley Additive exPlanations (SHAPs), the survival analysis of three key genes unveiled strong over-expression in the samples from "The Cancer Genome Atlas".
CONCLUSIONS
Our findings elucidate critical oncogenic drivers in OPSCC, offering vital insights for developing targeted therapies and enhancing understanding its pathogenesis.
Topics: Humans; Oropharyngeal Neoplasms; Biomarkers, Tumor; Papillomavirus Infections; Artificial Intelligence; Gene Expression Regulation, Neoplastic; Squamous Cell Carcinoma of Head and Neck; Algorithms; Sequence Analysis, RNA; Machine Learning; Papillomaviridae; Carcinoma, Squamous Cell
PubMed: 38940026
DOI: 10.31083/j.fbl2906220 -
Oncology Letters Aug 2024Thymic epithelial tumors (TETs) are rare and the major symptoms are not obvious until the tumor progresses to a relatively large size and compresses the surrounding...
Thymic epithelial tumors (TETs) are rare and the major symptoms are not obvious until the tumor progresses to a relatively large size and compresses the surrounding organs. As its growth is aggressive and it metastasizes to distant organs, it is important to find novel effective therapies. Lenvatinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, is approved as a drug therapy for thymic carcinoma (TC); however, although it is a molecular targeted therapy, there are no obvious predictors of therapeutic efficacy. The present study aimed to assess the association between clinicopathological factors and the protein expression of VEGFR, which is associated with tumor aggressiveness and the efficacy of VEGFR inhibitors. The VEGFR-2 protein expression was evaluated in 144 patients with TETs who underwent surgical resection. The present study assessed whether the expression of VEGFR-2 protein was associated with TET classification and pathological stage, progression-free survival and overall survival (OS). A total of 94 cases (65.2%) were positive for VEGFR-2 protein. The expression of VEGFR-2 was higher in the more aggressive type B3 thymoma and TC (88.5%) than in types A, AB, B1 and B2 thymoma (60.2%). The 5-year OS rate for the overall population was 53.1%. The 5-year OS rates of patients with negative VEGFR-2 staining score values (66.5%) were significantly longer than in patients with positive VEGFR-2 staining score values (42.5%; P=0.000078). Furthermore, the pathological stage was the only factor significantly associated with OS in multivariate analysis. The results of the present study suggest the possibility that the indications for VEGF inhibitor therapy could be extended to type B3 thymoma.
PubMed: 38939624
DOI: 10.3892/ol.2024.14516 -
JACC. Advances Feb 2024The number of patients with an arterial switch operation (ASO) for transposition of the great arteries (TGA) is steadily growing; limited information is available...
BACKGROUND
The number of patients with an arterial switch operation (ASO) for transposition of the great arteries (TGA) is steadily growing; limited information is available regarding the clinical course in the current era.
OBJECTIVES
The purpose was to describe clinical outcome late after ASO in a national cohort, including survival, rates of (re-)interventions, and clinical events.
METHODS
A total of 1,061 TGA-ASO patients (median age 10.7 years [IQR: 2.0-18.2 years]) from a nationwide prospective registry with a median follow-up of 8.0 years (IQR: 5.4-8.8 years) were included. Using an analysis with age as the primary time scale, cumulative incidence of survival, (re)interventions, and clinical events were determined.
RESULTS
At the age of 35 years, late survival was 93% (95% CI: 88%-98%). The cumulative re-intervention rate at the right ventricular outflow tract and pulmonary branches was 36% (95% CI: 31%-41%). Other cumulative re-intervention rates at 35 years were on the left ventricular outflow tract (neo-aortic root and valve) 16% (95% CI: 10%-22%), aortic arch 9% (95% CI: 5%-13%), and coronary arteries 3% (95% CI: 1%-6%). Furthermore, 11% (95% CI: 6%-16%) of the patients required electrophysiological interventions. Clinical events, including heart failure, endocarditis, and myocardial infarction occurred in 8% (95% CI: 5%-11%). Independent risk factors for any (re-)intervention were TGA morphological subtype (Taussig-Bing double outlet right ventricle [HR: 4.9, 95% CI: 2.9-8.1]) and previous pulmonary artery banding (HR: 1.6, 95% CI: 1.0-2.2).
CONCLUSIONS
TGA-ASO patients have an excellent survival. However, their clinical course is characterized by an ongoing need for (re-)interventions, especially on the right ventricular outflow tract and the left ventricular outflow tract indicating a strict lifelong surveillance, also in adulthood.
PubMed: 38939383
DOI: 10.1016/j.jacadv.2023.100772 -
Frontiers in Oncology 2024To assess the efficacy and safety of nimotuzumab in combination with radiotherapy or chemoradiotherapy for locally advanced head and neck squamous cell carcinoma.
Nimotuzumab combined with radiotherapy+/- chemotherapy for definitive treatment of locally advanced squamous cell carcinoma of head and neck: a metanalysis of randomized controlled trials.
OBJECTIVES
To assess the efficacy and safety of nimotuzumab in combination with radiotherapy or chemoradiotherapy for locally advanced head and neck squamous cell carcinoma.
METHODS
Systematic searches were performed on PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biomedical Medicine, Wanfang, VIP databases. Seven eligible randomized controlled trials (n = 1012) were selected through rigorous inclusion and exclusion criteria.
RESULTS
A total of 1012 cases were included. including 508 (50.2%) in the nimotuzumab combination treatment group; There were 504 cases (49.8%) in the control group. The results of meta-analysis showed that the overall survival (Hazard Ratio [HR]=0.75, 95% Confidence Interval [CI]: 0.62-0.90, P<0.05), progression-free survival (HR=0.69, 95% CI: 0.54-0.87, P<0.05), complete response rate (Risk Ratio [RR]=1.52, 95% CI: 1.24-1.86, P<0.05), and objective response rate (RR=1.32, 95% CI: 1.17-1.48, P<0.05) were significantly improved in the nimotuzumab combination treatment group compared with the control group. In terms of the incidence of adverse effects, only the incidence of rash was the nimotuzumab combination group higher than in the treatment alone group, and there was no significant difference between the remaining adverse reactions (neutropenia, anemia, nausea/vomiting, mucositis, dermatitis, dysphagia).
CONCLUSION
Nimotuzumab combined with radiotherapy or chemoradiotherapy is more effective than radiotherapy alone or chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck, and the safety profile is controllable. Therefore, the addition of nimotuzumab to treatment is expected to be an effective treatment option for this disease. However, more prospective randomized controlled trials are needed to fully explore the effectiveness of this treatment in patients with locally advanced head and neck squamous cell carcinoma.
SYSTEMATIC REVIEW REGISTRATION
identifier PROSPERO (CRD: 42022383313).
PubMed: 38939342
DOI: 10.3389/fonc.2024.1380428 -
Chemical Science Jun 2024Antimicrobial resistance (AMR) is a growing threat to health globally, with the potential to render numerous medical procedures so dangerous as to be impractical. There...
Antimicrobial resistance (AMR) is a growing threat to health globally, with the potential to render numerous medical procedures so dangerous as to be impractical. There is therefore an urgent need for new molecules that function through novel mechanisms of action to combat AMR. The bacterial DNA-repair and SOS-response pathways promote survival of pathogens in infection settings and also activate hypermutation and resistance mechanisms, making these pathways attractive targets for new therapeutics. Small molecules, such as IMP-1700, potentiate DNA damage and inhibit the SOS response in methicillin-resistant ; however, understanding of the structure-activity relationship (SAR) of this series is lacking. We report here the first comprehensive SAR study of the IMP-1700 scaffold, identifying key pharmacophoric groups and delivering the most potent analogue reported to date, OXF-077. Furthermore, we demonstrate that as a potent inhibitor of the mutagenic SOS response, OXF-077 suppresses the rate of ciprofloxacin resistance emergence in . This work supports SOS-response inhibitors as a novel means to combat AMR, and delivers OXF-077 as a tool molecule for future development.
PubMed: 38939155
DOI: 10.1039/d4sc00995a