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Alternative Therapies in Health and... Jun 2024The objective of this study is to develop a prediction model for the pathological upgrading of low-grade dysplasia (LGD) in gastric mucosa. The study aims to compare the...
OBJECTIVE
The objective of this study is to develop a prediction model for the pathological upgrading of low-grade dysplasia (LGD) in gastric mucosa. The study aims to compare the performance of a traditional model based on clinical and endoscopic factors with an enhanced model that incorporates AMACR staining of biopsy tissues.
METHODS
The study utilized a training dataset of 405 LGD cases to establish and compare the traditional and enhanced prediction models. Factors associated with upgrading were identified, and the traditional model was based on these factors. The enhanced model incorporated AMACR staining. The models' performances were evaluated using the area under the curve (AUC), bootstrap resampling, and decision curve analysis. External validation was performed using 171 LGD cases. Statistical techniques such as logistic regression and resampling methods were employed to assess the models' predictive abilities and robustness.
RESULTS
In the training dataset, the traditional model achieved an AUC of 0.824 (95% confidence interval [CI]: 0.783-0.865) for predicting pathological upgrading. However, the enhanced model, which incorporated AMACR staining, exhibited a significantly improved performance with an AUC of 0.878 (95% CI: 0.843-0.913). This increase in AUC by 0.054 (95% CI: 0.015-0.093) demonstrates a statistically significant enhancement provided by the inclusion of AMACR staining in the prediction model for pathological upgrading of LGD lesions in gastric mucosa.
CONCLUSION
The findings of this study highlight the practical implications of the enhanced prediction model incorporating AMACR staining for low-grade gastric mucosal dysplasia (LGD). The significantly improved performance of the enhanced model in predicting pathological upgrading emphasizes its potential to revolutionize the management and treatment strategies for patients with LGD. By providing a more accurate prediction of upgrading, the enhanced model enables early intervention and timely decision-making, leading to improved outcomes and prognosis for patients. The incorporation of AMACR staining in the prediction model holds promise for enhancing diagnostic strategies and reducing the incidence of postoperative pathological upgrading. This research underscores the importance of leveraging advanced techniques to improve the early detection rate of gastric cancer and ultimately benefit patient care.
PubMed: 38940773
DOI: No ID Found -
Cancer Biology & Medicine Jun 2024Targeted therapy is crucial for advanced colorectal cancer (CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs,... (Review)
Review
Targeted therapy is crucial for advanced colorectal cancer (CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs, existing standard molecular pathological detection systems and therapeutic strategies can no longer meet the requirements for careful management of patients with advanced CRC. Thus, rare genetic variations require diagnosis and targeted therapy in clinical practice. Rare gene mutations, amplifications, and rearrangements are usually associated with poor prognosis and poor response to conventional therapy. This review summarizes the clinical diagnosis and treatment of rare genetic variations, in genes including erb-b2 receptor tyrosine kinase 2 (ERBB2), B-Raf proto-oncogene, serine/threonine kinase (BRAF), ALK receptor tyrosine kinase/ROS proto-oncogene 1, receptor tyrosine kinase (ALK/ROS1), neurotrophic receptor tyrosine kinases (NTRKs), ret proto-oncogene (RET), fibroblast growth factor receptor 2 (FGFR2), and epidermal growth factor receptor (EGFR), to enhance understanding and identify more accurate personalized treatments for patients with rare genetic variations.
Topics: Humans; Colorectal Neoplasms; Proto-Oncogene Mas; Genetic Variation; Mutation; Proto-Oncogene Proteins c-ret; Molecular Targeted Therapy; Proto-Oncogene Proteins B-raf; Precision Medicine; Biomarkers, Tumor; Protein-Tyrosine Kinases; Proto-Oncogene Proteins
PubMed: 38940668
DOI: 10.20892/j.issn.2095-3941.2024.0026 -
The Oncologist Jun 2024Given the typical trajectory of glioblastoma, many patients lose decision-making capacity over time, which can lead to inadequate advance care planning (ACP) and...
BACKGROUND
Given the typical trajectory of glioblastoma, many patients lose decision-making capacity over time, which can lead to inadequate advance care planning (ACP) and end-of-life (EOL) care. We aimed to evaluate patients' current ACP and EOL care status.
PATIENTS AND METHODS
We conducted a cohort study on 205 patients referred to oncologists at a Korean tertiary hospital between 2017 and 2022. We collected information on sociodemographic factors, cancer treatment, palliative care consultation, ACP, legal documents on life-sustaining treatment (LST) decisions, and aggressiveness of EOL care.
RESULTS
With a median follow-up time of 18.3 months: 159 patients died; median overall survival: 20.3 months. Of the 159 patients, 11 (6.9%) and 63 (39.6%) had advance directive (AD) and LST plans, respectively, whereas 85 (53.5%) had neither. Among the 63 with LST plans, 10 (15.9%) and 53 (84.1%) completed their forms through self-determination and family determination, respectively. Of the 159 patients who died, 102 (64.2%) received palliative care consultation (median time: 44 days from the first consultation to death) and 78 (49.1%) received aggressive EOL care. Those receiving palliative care consultations were less likely to receive aggressive EOL care (83.3% vs 32.4%, P < .001), and more likely to use more than 3 days of hospice care at EOL (19.6% vs 68.0%, P < .001).
CONCLUSIONS
The right to self-determination remains poorly protected among patients with glioblastoma, with nearly 90% not self-completing AD or LST plan. As palliative care consultation is associated with less aggressive EOL care and longer use of hospice care, physicians should promptly introduce patients to ACP conversations and palliative care consultations.
PubMed: 38940449
DOI: 10.1093/oncolo/oyae159 -
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 -
Animal Models and Experimental Medicine Jun 2024Short-chain fatty acids (SCFAs) are major metabolites produced by the gut microbiota through the fermentation of dietary fiber, and they have garnered significant... (Review)
Review
Short-chain fatty acids (SCFAs) are major metabolites produced by the gut microbiota through the fermentation of dietary fiber, and they have garnered significant attention due to their close association with host health. As important mediators between the gut microbiota and the host, SCFAs serve as energy substrates for intestinal epithelial cells and maintain homeostasis in host immune and energy metabolism by influencing host epigenetics, activating G protein-coupled receptors, and inhibiting pathogenic microbial infections. This review provides a comprehensive summary of SCFAs synthesis and metabolism and offering an overview of the latest research progress on their roles in protecting gut health, enhancing energy metabolism, mitigating diseases such as cancer, obesity, and diabetes, modulating the gut-brain axis and gut-lung axis, and promoting bone health.
PubMed: 38940192
DOI: 10.1002/ame2.12464 -
Frontiers in Bioscience (Landmark... Jun 2024Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic approach for a variety of diseases due to their immunomodulatory and tissue regeneration... (Review)
Review
Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic approach for a variety of diseases due to their immunomodulatory and tissue regeneration capabilities. Despite their potential, the clinical application of MSC therapies is hindered by limited cell retention and engraftment at the target sites. Electrospun scaffolds, with their high surface area-to-volume ratio and tunable physicochemical properties, can be used as platforms for MSC delivery. However, synthetic polymers often lack the bioactive cues necessary for optimal cell-scaffold interactions. Integrating electrospun scaffolds and biological polymers, such as polysaccharides, proteins, and composites, combines the mechanical integrity of synthetic materials with the bioactivity of natural polymers and represents a strategic approach to enhance cell-scaffold interactions. The molecular interactions between MSCs and blended or functionalized scaffolds have been examined in recent studies, and it has been shown that integration can enhance MSC adhesion, proliferation, and paracrine secretion through the activation of multiple signaling pathways, such as FAK/Src, MAPK, PI3K/Akt, Wnt/β-catenin, and YAP/TAZ. Preclinical studies on small animals also reveal that the integration of electrospun scaffolds and natural polymers represents a promising approach to enhancing the delivery and efficacy of MSCs in the context of regenerating bone, cartilage, muscle, cardiac, vascular, and nervous tissues. Future research should concentrate on identifying the distinct characteristics of the MSC niche, investigating the processes involved in MSC-scaffold interactions, and applying new technologies in stem cell treatment and biofabrication to enhance scaffold design. Research on large animal models and collaboration among materials scientists, engineers, and physicians are crucial to translating these advancements into clinical use.
Topics: Humans; Mesenchymal Stem Cells; Tissue Scaffolds; Mesenchymal Stem Cell Transplantation; Animals; Polymers; Tissue Engineering
PubMed: 38940050
DOI: 10.31083/j.fbl2906228 -
Frontiers in Bioscience (Landmark... Jun 2024The treatment options for multiple myeloma (MM) have undergone significant transformation with the advent of immunotherapy. Novel therapies that focus on tumor antigens... (Review)
Review
The treatment options for multiple myeloma (MM) have undergone significant transformation with the advent of immunotherapy. Novel therapies that focus on tumor antigens now drive advances in MM research. Bispecific antibodies (bsAbs) leverage revolutionary advances in bioengineering techniques and embody the second generation of antibody-based tumor therapy. Recent studies on bsAbs in relapsed/refractory MM cases have revealed remarkable efficacy and acceptable safety profiles. The approval of elranatamab and teclistamab represents the next step in the development of bsAbs for the treatment of MM. This review article addresses the antigen targeting, efficacy, safety, and strategies in the application of bsAbs against treatment-resistant MM, with a focus on clinical trials and real-world data.
Topics: Multiple Myeloma; Antibodies, Bispecific; Humans; Immunotherapy; Antigens, Neoplasm; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological
PubMed: 38940040
DOI: 10.31083/j.fbl2906216 -
Journal of Extracellular Biology Feb 2024The interferon stimulated gene 15 (ISG15), a ubiquitin like protein and its conjugates have been implicated in various human malignancies. However, its role in ovarian...
The interferon stimulated gene 15 (ISG15), a ubiquitin like protein and its conjugates have been implicated in various human malignancies. However, its role in ovarian cancer progression and metastasis is largely unknown. In high grade serous ovarian cancer (HGSOC), ascites is the major contributor to peritoneal metastasis. In this study, we identified significantly elevated ISG15 protein expression in HGSOC patient ascites, ascites derived primary ovarian cancer cells (POCCs), POCC small extracellular vesicles (sEVs) as well as metastatic tissue. Our results demonstrates that ISG15 increases exocytosis in ascites-derived POCCs by decreasing the endosome-lysosomal fusion, indicating a key role in sEV secretion. Further, knockdown (KD) of ISG15 resulted in a significant decrease in vesicles secretion from HGSOC cells and mouse models, leading to reduced HGSOC cell migration and invasion. Furthermore, our pre-clinical mouse model studies revealed the influence of vesicular ISG15 on disease progression and metastasis. In addition, knockdown of ISG15 or using the ISG15 inhibitor, DAP5, in combination therapy with carboplatin showed to improve the platinum sensitivity in-vitro and reduce tumour burden in-vivo. We also found that ISG15 expression within sEV represents a promising prognostic marker for HGSOC patients. Our findings suggest that ISG15 is a potential therapeutic target for inhibiting progression and metastasis in HGSOC and that vesicular ISG15 expression could be a promising biomarker in the clinical management of ovarian cancer. : High-grade serous ovarian cancer (HGSOC) has high morbidity and mortality rates, but its progression and metastasis are still poorly understood, and there is an urgent need for early detection and targeted therapies. Our study presents novel findings that implicate ISG15-mediated vesicular proteins in the advancement and spread of HGSOC. These results offer pre-clinical evidence of potential new molecular targets, prognostic markers and therapeutic strategies for HGSOC that could ultimately enhance patient survival.
PubMed: 38939897
DOI: 10.1002/jex2.92 -
Chemical & Biomedical Imaging Jun 2024There is significant and increasing interest in using the photothermal effect to record infrared (IR) absorption spectra localized to volumes that are considerably...
There is significant and increasing interest in using the photothermal effect to record infrared (IR) absorption spectra localized to volumes that are considerably smaller than the wavelength of excitation, i.e., subdiffraction imaging. As opposed to conventional IR microscopy, in which absorption and scattering of the illuminating light is measured, subdiffraction imaging can be achieved through detection of the sample's thermal response to IR absorption-induced heating. While this relationship has been examined by a variety of coarse-grained models, a generalized analysis of the dependence of temperature and surface deformation arising from an absorber below the surface has not been reported. Here, we present an analytical model to understand a sample's thermoelastic response in photothermal measurements. The model shows important dependence of the ability to record subdiffraction data on modulation frequency of exciting light, limitations imposed by optical sensing, and the potential to discern location of objects ultimately limited by noise and sharpness of the detecting mechanism. This foundational analysis should allow for better modeling, understanding, and harnessing of the relationship between absorption and sample response that underlies IR photothermal measurements.
PubMed: 38939874
DOI: 10.1021/cbmi.4c00018 -
Exploration (Beijing, China) Jun 2024Protein-based drugs have shown unique advantages to treat various diseases in recent years. However, most protein therapeutics in clinical use are limited to...
Protein-based drugs have shown unique advantages to treat various diseases in recent years. However, most protein therapeutics in clinical use are limited to extracellular targets with low delivery efficiency. To realize targeted protein delivery, a series of stimuli-triggered nanoparticle formulations have been developed to improve delivery efficiency and reduce off-target release. These smart nanoparticles are designed to release cargo proteins in response to either internal or external stimuli at pathological tissues. In this way, varieties of protein-based drugs including antibodies, enzymes, and pro-apoptotic proteins can be effectively delivered to desired sites for the treatment of cancer, inflammation, metabolic diseases, and so on with minimal side effects. In this review, recent advances in the design of stimuli-triggered nanomedicine for targeted protein delivery in different biomedical applications will be discussed. A deeper understanding of these emerging strategies helps develop more efficient protein delivery systems for clinical use in the future.
PubMed: 38939867
DOI: 10.1002/EXP.20230025