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The diverse landscape of RNA modifications in cancer development and progression
No full textBACKGROUND: RNA modifications, a central aspect of epitranscriptomics, add a regulatory layer to gene expression by modifying RNA function without altering nucleotide sequences. These modifications play vital roles across RNA species, influencing RNA stability, translation, and interaction dynamics, and are regulated by specific enzymes that add, remove, and interpret these chemical marks. OBJECTIVE: This review examines the role of aberrant RNA modifications in cancer progression, exploring their potential as diagnostic and prognostic biomarkers and as therapeutic targets. We focus on how altered RNA modification patterns impact oncogenes, tumor suppressor genes, and overall tumor behavior. METHODS: We performed an in-depth analysis of recent studies and advances in RNA modification research, highlighting key types and functions of RNA modifications and their roles in cancer biology. Studies involving preclinical models targeting RNA-modifying enzymes were reviewed to assess therapeutic efficacy and potential clinical applications. RESULTS: Aberrant RNA modifications were found to significantly influence cancer initiation, growth, and metastasis. Dysregulation of RNA-modifying enzymes led to altered gene expression profiles in oncogenes and tumor suppressors, correlating with tumor aggressiveness, patient outcomes, and response to immunotherapy. Notably, inhibitors of these enzymes demonstrated potential in preclinical models by reducing tumor growth and enhancing the efficacy of existing cancer treatments. CONCLUSIONS: RNA modifications present promising avenues for cancer diagnosis, prognosis, and therapy. Understanding the mechanisms of RNA modification dysregulation is essential for developing targeted treatments that improve patient outcomes. Further research will deepen insights into these pathways and support the clinical translation of RNA modification-targeted therapies
Growth Prediction Model for Prepubertal Children With Idiopathic Growth Hormone Deficiency: An Analysis of LG Growth Study Data
No full textBACKGROUND: Growth hormone (GH) treatment is effective in restoring normal growth in children with GH deficiency (GHD). However, individual responses to GH treatment vary, necessitating predictive models to estimate growth outcomes. This study aimed to develop and validate a predictive model for GH treatment response during the first 2 years in patients with idiopathic GHD using the LG growth study (LGS) database. METHODS: This observational study included 669 prepubertal patients with idiopathic GHD from the LGS registry who received GH treatment for at least 2 years. Clinical and laboratory data were collected at baseline and every 6 months thereafter. Stepwise multivariate regression analysis was performed to develop prediction models for the treatment period. RESULTS: The mean age of patients with GDH was 6.0 +/- 1.8 years. Height standard deviation score (SDS) significantly increased from -2.50 +/- 0.71 to -1.66 +/- 0.71 in the first year and -1.35 +/- 0.71 in the second year. The first-year growth velocity was 9.06 +/- 1.51 cm, decreasing to 7.42 +/- 1.37 cm in the second year. The prediction models incorporated variables such as age, birth weight, bone age, initial height SDS, body mass index SDS, mid-parental height, GH dose and first year of height after GH treatment, explaining 76.9% and 84.1% of the variability in height SDS changes in the first and second years, respectively. CONCLUSIONS: GH treatment significantly improves height outcomes in prepubertal children with GHD. The developed predictive models demonstrated accuracy, facilitating personalized GH therapy. Future research should focus on refining these models and exploring the long-term effects of GH treatment in pubertal patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01604395
Altered triple network model connectivity is associated with cognitive function and depressive symptoms in older adults
No full textINTRODUCTION: Late-life cognitive impairment and depression frequently co-occur and share many symptoms. However, the specific neural and clinical factors contributing to both their common and distinct profiles in older adults remain unclear. METHODS: We investigated resting-state correlates of cognitive and depressive symptoms in older adults (n = 248 and n = 95) using clinical, blood, and neuroimaging data. We computed a connectivity matrix across default mode, executive control, and salience networks. Cross-validated elastic net regression identified features reflecting cognitive function and depressive symptoms. These features were validated on a held-out dataset. RESULTS: We discovered that white matter hyperintensities and nine overlapping nodes spanning all three networks are associated with both cognitive function and depressive symptoms, including left amygdala, left hippocampus, and bilateral ventral tegmental area. DISCUSSION: Our findings reveal intertwined neural nodes influencing cognitive impairment and depressive symptoms in late life, offering insights into shared characteristics and potential therapeutic targets. HIGHLIGHTS: Resting-state neuroimaging markers are associated with symptoms of cognitive decline and late-life depression. Symptom-associated connectivity alterations were present across three major brain networks of interest, including the salience, default mode, and executive control networks. Some regions of interest are associated with both cognitive function and depressive symptoms, including the left amygdala, left hippocampus, and bilateral ventral tegmental area
RIPK3 in necroptosis and cancer
No full textReceptor-interacting protein kinase-3 is essential for the cell death pathway called necroptosis. Necroptosis is activated by the death receptor ligands and pattern recognition receptors of the innate immune system, leading to significant consequences in inflammation and in diseases, particularly cancer. Necroptosis is highly proinflammatory compared with other modes of cell death because cell membrane integrity is lost, resulting in releases of cytokines and damage-associated molecular patterns that potentiate inflammation and activate the immune system. We discuss various ways that necroptosis is triggered along with its potential role in cancer and therapy
Artificial intelligence-based gastric cancer detection in the gastric submucosal dissection method via hyperspectral imaging
No full textAlthough endoscopy is a standard diagnostic tool for detecting gastric cancer, challenges persist in identifying cancer and assessing tumor extent, particularly in stomachs with atrophy and intestinal metaplasia. To address this issue, we aimed to introduce a novel, compact hyperspectral imaging system with artificial intelligence (AI) that utilizes structured illumination and hyperspectral imaging to diagnose gastric cancer based on intrinsic tissue optical properties. The optical properties of three types of gastric tissue (normal, adenoma, and gastric cancer) obtained from nine patients collected via endoscopic submucosal dissection were analyzed. Our findings reveal that cancer tissue displays unique optical properties, such as low reduced scattering coefficients and distinct reflectance spectral profiles when compared to normal and adenoma tissues. However, it was challenging to diagnose gastric cancer accurately using optical properties with conventional analysis methods due to their heterogeneity. Therefore, we employed a Vision Transformer model with a supervised learning approach to accurately classify tissue types based on intrinsic optical properties. To accurately train the AI model, we devised a novel image processing method to obtain single-pixel level ground-truth labeling data by aligning pathology results and imaging data. The trained AI model successfully demonstrated its ability to diagnose gastric cancer accurately in the nine patients studied. Given its compact design and rapid imaging capabilities, the proposed optical system can be a versatile clinical tool for on-site endoscopic diagnosis and could potentially aid in complete endoscopic tumor removal
생체 의료 적용을 위한 3D 프린팅 지지체 제작 및 표면 최적화 기술
No full textThree-dimensional (3D) printing is one of the most effective scaffold manufacturing techniques which might revolutionize the realm of tissue engineering and regenerative medicine. The scaffolds, one of the major elements of tissue engineering, along with growth factors and cells, are still one of the most promising approaches for developing organ regeneration. However, the applications of 3D-printed hard scaffolds might have limitations due to their poor surface properties, which play a crucial role in cell recruitment and infiltration, tissue-scaffold integration, and anti-inflammatory properties. Various prerequisites have been suggested for clinical applications of 3D-printed substitute for human body. Consequently, continuous amendment has been made to modify the surface properties, porosities and mechanical properties of these scaffolds. The techniques that modify the surfaces through chemical and material modifications can also be applied to facilitate the efficacy of these scaffolds. In this review, we summarized the characteristics of 3D printing technology and discuss the development direction of the latest 3D printing technology toward meeting the unmet needs in the clinic
Tumor Regulatory Effect of 15-Hydroxyprostaglandin Dehydrogenase (HPGD) in Triple-Negative Breast Cancer
No full textProstaglandin regulation is known to play a pivotal role in tumorigenesis; however, the contributions of the prostaglandin-metabolizing enzyme 15-hydroxyprostaglandin dehydrogenase (HPGD) to cancer development remain poorly understood. In this study, we investigate the effects of HPGD on cell viability, proliferation, anchorage-independent growth, and migration in triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer. Overexpression of HPGD in human TNBC cells resulted in both positive and negative regulation of cell proliferation and colony formation, with these effects occurring independent of prostaglandin E2 (PGE(2)). In contrast, overexpression of the mouse homolog, Hpgd, in murine TNBC cells led to a consistent but modest reduction in cell viability and colony formation, indicating that HPGD activity varies depending on species and cell line context. Notably, TNBC cells expressing a mutant form of Hpgd (Hpgd(mut)), which lacks the ability to bind PGE(2), exhibited similar functional outcomes in cell viability and colony formation as those expressing wild-type Hpgd (Hpgd(WT)). These findings suggest that HPGD may exert its tumorigenic effects through non-enzymatic mechanisms, potentially by involving modulation of KRAS signaling in human TNBC cells. Our results highlight the diverse roles of HPGD in cancer biology, particularly in the context of TNBC, and point to non-enzymatic pathways as a significant aspect of its tumorigenic activity
Survival benefit of adjuvant chemotherapy in high-risk patients with colon cancer regardless of microsatellite instability
No full textINTRODUCTION: The predictive utility of high-risk features (HRFs) and microsatellite instability (MSI) status for adjuvant chemotherapy (ACT) in patients with stage II colon cancer remains unclear. We examined the impact of HRFs and MSI in predicting the benefits of adjuvant ACT in patients with stage II colon cancer. MATERIALS AND METHODS: We included 1801 patients with resected stage II colon cancer who underwent ACT (5-fluorouracil [FU] and oxaliplatin) or surgery alone between January 2010 and December 2017. The primary outcomes were overall survival (OS) and disease-free survival (DFS). RESULTS: Among MSI-high patients with HRFs, patients who received 5- FU and oxaliplatin-based ACT had significantly higher OS and DFS than patients who did not, with no significant difference between those who received 5-FU and oxaliplatin as ACT. Among MSI-low/microsatellite stable patients with HRFs, patients who received 5-FU and oxaliplatin as ACT had significantly higher OS and DFS than patients who did not, with no significant differences between those who received 5-FU and oxaliplatin as ACT. Among patients who did not receive ACT, OS and DFS were 95.0 % and 91.2 % for patients without HRFs, respectively, and 84.4 % and 75.0 % for patients with HRFs, respectively. ACT improved the survival rates of patients with HRFs (OS: 84.4 %-->95.9 %, DFS: 75.0 %-->88.9 %). CONCLUSIONS: ACT can be recommended for patients having stage II colon cancer with one or more HRF(s) for recurrence, regardless of the MSI status. In patients with HRFs, we observed no significant difference regarding survival between those who received 5-FU and oxaliplatin-based ACT
Development of metastatic lung adenocarcinoma in a twenty-year-old skin graft site on the scalp: A case report
No full textDevelopment of a digital micromirror device-based hyperspectral imaging system with dynamically adjustable measurement regions
No full textHyperspectral imaging (HSI) captures both spatial and spectral information simultaneously, enabling accurate discrimination of targets that are difficult to distinguish using conventional color imaging techniques. As a result, HSI has been widely applied across various fields, including remote sensing, industrial inspection, and biomedical diagnostics. Although many HSI methods have been developed, their imaging specifications-such as spatial and spectral resolution and acquisition speed-are largely constrained by the optical components employed. These limitations pose significant challenges in dynamic imaging environments or when the target's size and shape vary over time. In this study, we present a novel HSI technique utilizing a digital micromirror device (DMD) to enable high spectral resolution imaging with adjustable spectral acquisition regions. The DMD operates in a binary mode, reflecting light toward two discrete angles based on input patterns, thereby facilitating the simultaneous acquisition of spectral data and wide-field images. The spectral acquisition regions are clearly visualized as darkened areas in the wide-field image, eliminating the need for post-imaging registration. The proposed DMD-based HSI method demonstrates high fidelity in spectral data acquisition and enables spatially resolved spectral imaging. Additionally, we validate its applicability to biomedical applications by successfully differentiating spectral profiles of normal and cancerous tissues from a H&E-stained slide. Collectively, the DMD-based HSI approach offers a versatile and practical imaging solution in cases requiring high spectral resolution under dynamic imaging conditions