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At least 109 records · Page 6Linked to original sources
PubMed2026

Integrated multi-omics analysis and functional experiments reveals PPAP2C as a potential prognostic biomarker and therapeutic target in breast cancer.

BACKGROUND: This study aims to systematically elucidate the clinical significance and biological function of the phospholipid phosphatase (PLPP) family member (PPAP2C) phosphatidic acid phosphatase type 2C in breast cancer, and to evaluate its potential as a prognostic biomarker and therapeutic target. METHODS: Gene expression data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases were integrated to characterize the expression profile of PLPP family members, focusing on PPAP2C in breast cancer. The prognostic value of PPAP2C, initially identified at the mRNA level (TCGA, (METABRIC) Molecular Taxonomy of Breast Cancer International Consortium, Gene Expression Omnibus (GEO)), was confirmed at the protein level by immunohistochemistry (IHC) on tissue microarrays (TMA). The oncogenic functions of PPAP2C were investigated in triple-negative breast cancer (TNBC) cells through CRISPR-Cas9-mediated knockout and ectopic overexpression, with assessment of key phenotypes including proliferation, colony formation, migration, and invasion. In vivo validation was subsequently performed using an MDA-MB-231 xenograft model. RESULTS: PPAP2C exhibits the most significant overexpression pattern across 33 cancer types (upregulated in 16 cancers, downregulated in only 3). Compared with normal tissues, PPAP2C showed specific overexpression in breast cancer tissues and was significantly associated with advanced clinical stages and aggressive subtypes (HER2+ and TNBC). Survival analysis demonstrated that high PPAP2C expression correlated with significantly shorter overall survival and disease-free survival, which was further validated in METABRIC and GEO cohorts. Tissue microarray analysis confirmed higher PPAP2C protein positivity in tumor tissues (94.7%) than in adjacent normal tissues (59.7%), with worse OS and RFS in high-expression groups. Multivariate analysis identified PPAP2C as an independent prognostic factor for OS. Functional experiments revealed that PPAP2C knockout (via 5-bp/1-bp frameshift mutations) suppressed TNBC cell proliferation, colony formation, migration, and invasion, while overexpression enhanced these phenotypes. In vivo studies further demonstrated complete tumor regression in MDA-MB-231 xenografts upon PPAP2C knockout. CONCLUSION: This study identifies PPAP2C as a key oncogenic driver and a robust independent prognostic biomarker in breast cancer. The findings provide compelling evidence that PPAP2C represents a promising therapeutic target, offering a new strategic avenue for precision therapy, particularly for aggressive breast cancer subtypes.

PLPP2↗
PubMed2026

[State Changes and Stability Grading of Driver Genes in Non-small Cell Lung Cancer Based on Repeated NGS Testing].

BACKGROUND: Next-generation sequencing (NGS)-based driver gene testing has become a routine component of molecular subtyping and precision therapy for non-small cell lung cancer (NSCLC). Dynamic genomic monitoring facilitates early detection of resistance-related molecular alterations and informs timely therapeutic adjustments. However, standardized criteria for evaluating the stability of serial NGS testing are currently lacking, and the applicability of NGS using formalin-fixed paraffin-embedded (FFPE) specimens for dynamic monitoring remains poorly defined. This study aims to establish a stability grading system for driver gene status alterations based on repeated NGS testing, and to provide evidence-based support for clinical repeat biopsy strategies. METHODS: Data from 1232 patients with NSCLC who underwent two or more NGS tests on FFPE tissue specimens at Beijing Chest Hospital between June 2019 and April 2026 were collected retrospectively. Patients with an interval of &#x2265;4 months between the initial and last tests were included to ensure the representativeness of temporal analysis, resulting in a main analysis cohort of 942 patients. The Kappa consistency test was used to evaluate the state stability of nine core driver genes [epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), mesenchymal&#x2011;epithelial transition factor (MET), rearranged during transfection (RET), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), erb&#x2011;b2 receptor tyrosine kinase 2 (ERBB2), and phosphatidylinositol&#x2011;4,5&#x2011;bisphosphate 3&#x2011;kinase catalytic subunit alpha (PIK3CA)] and to construct a five&#x2011;level grading system. Paired variant allele frequency (VAF) differences were compared using the Wilcoxon signed&#x2011;rank test. Independent influencing factors for mutation accumulation were identified by binary Logistic regression. RESULTS: The state stability of the nine genes was classified into five levels: EGFR showed high stability (Kappa=0.838), ROS1/ALK/KRAS good stability, BRAF/PIK3CA/RET moderate stability, and ERBB2 low stability, and MET showed high instability. MET exhibited the highest rate of state change (9.3%) with a raw observed agreement of 90.7%. Its Kappa value (0.172) was influenced by the low prevalence (3.7%) compression effect and should therefore be interpreted alongside the observed agreement (90.7%) and the prevalence-adjusted and bias-adjusted Kappa (PABAK). The VAF of PIK3CA increased significantly (P=0.005). T790M positivity increased from 5.8% to 10.8%, and 30 new C797S mutations were detected at the last test (13 with T790M, 17 without). The overall rate of new driver gene variants in the main cohort was 18.0%. Binary Logistic regression showed that a lower number of initial mutated genes was the only independent predictor of new variants [odds ratio (OR)=0.399, P<0.001], while sex and detection interval showed no independent association. CONCLUSIONS: A five level stability grading system for state changes of driver genes in NSCLC based on repeated NGS testing has been established. MET showed the most frequent state changes, which should be interpreted in conjunction with the prevalence effect. The VAF increase of PIK3CA is an observational finding, and its clinical significance requires further prospective validation. A lower initial mutation burden may reflect tumor clonal complexity and was associated with a higher likelihood of subsequent acquisition of new variants. FFPE based NGS is applicable for repeated testing at clinical treatment decision nodes.

Humans↗
PubMed2025

Stem cell derived neural organoid approaches for neurological diseases.

Traditional two-dimensional cultures and animal models often fall short in capturing the complexities of neurodevelopmental and neurodegenerative diseases. However, recently developed neural organoid approaches, three-dimensional structures derived from human pluripotent stem cells, have become powerful tools for modeling human neuronal development and disease. Unlike traditional models, neural organoids provide significant insights and improved modeling capabilities. Here, we explore various types of neural organoids in disease modeling and outline distinct protocols for generating each type, including specific patterning methods, growth factors, and differentiation durations. The potential and advantages of co-culturing neural organoids with other cells and tissues are also discussed. While neural organoids have already made significant contributions to neuroscience research, future directions should focus on enhancing their maturation and functionality. The progression of neural organoids approaches will generate more accurate and comprehensive disease models, ultimately adding to our understanding of disease pathogenesis and paving the way for future precision therapies for neurological diseases.

neural differentiation↗
PubMed2001

Impact of a broadband interactive televisit/teleconsultation service for residential and working environments.

The availability of health care attention at the point of need is one of the key benefits of telemedicine. Home environment and working place are the two scenarios selected in this article to evaluate the impact of a televisit and teleconsultation service. 31 users from four different medical and patient groups participated in this study supported by European Commission ATTRACT project. The experiences, carried out in Madrid and Valencia Spanish sites, benefited from interactive broadband access networks to provide cost-effective telecare services. Key areas analyzed encompass systems usability, clinical outcomes, patients quality of care and infoethic issues. Services advantages were verified and compared both from patients and medical staff points of view. Main benefits pointed out refer to displacement reduction, better communication doctor/patient, provision of comfort or friendliness, more precise therapy follow-up and increases in patients sense of well being.

Attitude of Health Personnel↗
PubMedDate not supplied

[Analysis of adrenocortical tumors morphology as regards their structure and potential malignancy].

INTRODUCTION: A consequence of diagnosis of adrenocortical carcinoma (ACC) is introduction of pharmacological therapy, precise monitoring of the patients and in some cases re-operation. The aim of the study is to analyse morphology of adrenocortical tumours as regards their malignancy by use of criteria proposed by Weiss. MATERIAL AND METHODS: 110 adrenocortical tumours in 107 patients were analysed (M 27.1%, F 72.9%; age 32 to 77 years, mean 55.2 +/- 9.7). Conn syndrome was diagnosed in 16 patients (14.9%), Cushing syndrome in 12 (11.2%), and virilisation in 3 (2.8%). In 76 patients (71.0%) biochemical tests did not reveal hormonal hyperactivity of the tumour. RESULTS: In routine histopatological examination ACC was diagnosed in 6 tumours (5.4%), adrenocortical adenoma (ACA) in 92 (83.6%) and adrenocortical hyperplasia in 12 (10.9%). Nuclear grade III or IV was observed in 8 tumours (7.3%), mitotic rate > 5/50 high power fields in 6 (5.4%), atypical mitoses in 5 (4.5%), clear cells constituting < 25% of the tumour in 10 (9.1%), diffuse architecture in 8 (7.3%), necrosis in 16 (14.5%), veins infiltration in 4 (3.6%), sinusoids infiltration in 7 (6.3%), and tumour capsule infiltration in 5 (4.5%). Among ACC tumours 4-9 features of malignancy were present, among ACA--0-3 features. Statistical analysis revealed correlation between number of criteria proposed by Weiss and maximal tumour size (p < 0.05). CONCLUSION: The structure and cell arrangement in adrenocortical adenoma are heterogeneous. Application of criteria proposed by Weiss in histopathological examination of adrenocortical tumours can be useful in differentiating adrenocortical adenoma from carcinoma.

Adrenal Cortex Neoplasms↗
PubMed2006

Arteriopathy in the high-performance athlete.

Pain occurs frequently in high-performance athletes and is most often due to musculoskeletal injury or strain. However, athletes who participate in sports that require highly frequent, repetitive limb motion can also experience pain from an underlying arteriopathy, which causes exercise-induced ischemia. We reviewed the clinical records and follow-up care of 3 high-performance athletes (mean age, 29.3 yr; range, 16-47 yr) who were admitted consecutively to our institution from January 2002 through May 2003, each with a diagnosis of limb ischemia due to arteriopathy. The study group comprised 3 males: 2 active in competitive baseball (ages, 16 and 19 yr) and a cyclist (age, 47 yr). Provocative testing and radiologic evaluation established the diagnoses. Treatment goals included targeted resection of compressive structures, arterial reconstruction to eliminate stenosis and possible emboli, and improvement of distal perfusion. Our successful reconstructive techniques included thoracic outlet decompression and interpositional bypass of the subclavian artery in the 16-year-old patient, pectoralis muscle and tendon decompression to relieve compression of the axillary artery in the 19-year-old, and patch angioplasty for endofibrosis affecting the external iliac artery in the 47-year-old. Each patient was asymptomatic on follow-up and had resumed participation in competitive athletics. The recognition and anatomic definition of an arteriopathy that produces exercise-induced ischemia enables the application of precise therapy that can produce a symptom-free outcome and the ability to resume competitive athletics.

Adolescent↗
PubMedDate not supplied

Strabismus in patients over the age of 60 years.

We studied all cases of strabismus surgery performed at the Manhattan Eye, Ear and Throat Hospital between January 1, 1981 and June 30, 1986. Of the procedures, 106 (5.4%) were performed on patients over the age of 60 years. Strabismus in patients over age 60 represents a category of diseases which are different from those of childhood. Horizontal deviations were seen in 74% of the patients equally divided between esotropia and exotropia. Vertical strabismus was seen in 17%, and a combined vertical horizontal strabismus was seen in 9% of patients. In children, the overwhelming majority of ocular deviations are horizontal, with esotropias outnumbering exotropias. The strabismus was of adult onset in 71% of cases and of childhood onset in 29% of the patients. The etiology in the adult onset strabismus group included neuroparalytic, restrictive, sensory, and post-cataract surgery strabismus, as well as decompensated exophoria/intermittent exotropia; this was in contrast to children where the most common etiology of strabismus is innervational disturbances in fusional vergences. The major indications for surgery were diplopia and aesthenopia in 71% of cases. Diplopia is uncommon in childhood. Corrective surgery for the relief of diplopia may be enhanced with the use of adjustable sutures and postoperative prism therapy. Precise realignment is the goal of strabismus surgery in all age groups, however, the role of adjustable sutures and prisms is more important in the treatment of the functional complaints of older patients. Exploration and lysis of adhesions and scar tissue are major components of surgery on patients with restrictive strabismus.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

[Left ventricular asynergy in patients with impending myocardial infarction: two-dimensional echocardiographic assessment].

To determine the clinical significance of regional left ventricular asynergy in patients with impending myocardial infarction, we recorded two-dimensional echocardiograms (2DE) serially and performed coronary angiography immediately after the hospital admission in nine patients with initial impending infarction and their last anginal attacks were within 48 hours. Left ventricular asynergy on the first 2DE was observed in six of nine patients during symptom-free periods (Group A: LV asynergy group). Five of the six patients had significant coronary artery lesions (greater than or equal to 75% stenosis) in at least one major coronary artery. Intracoronary filling defects were detected in four of the five patients. Another three patients without asynergy (Group B) had significant fixed stenosis. Coronary artery spasm was observed in two patients during coronary angiography, but no patient had intracoronary filling defects. Intracoronary nitroglycerin (0.1-0.3 mg) reduced the severity of coronary artery narrowing in two patients. In addition, urokinase (240,000-480,000 IU) via the corresponding vessel (PTCR) in the remaining seven patients resulted in reduction in the severity of coronary artery stenosis in four patients, but not in the remaining three patients. Left ventricular wall movement in the asynergy group improved rapidly and no asynergy was observed by the seventh hospital day in five of the six patients. Successful PTCR treatment resulted in improvement of left ventricular wall movement. No asynergy was found in the non-asynergy group throughout their hospitalizations. These findings indicated that abnormal left ventricular wall movement is found in patients with impending myocardial infarction, even during symptom-free periods, but the wall movement gradually improves. The 2DE observations are useful for estimating the clinical status and for planning precise therapy for impending myocardial infarction.

Adult↗
PubMed1997

Glomerular changes in normo- and microalbuminuric patients with long-standing insulin-dependent diabetes mellitus.

Normalbuminuric patients who have long-standing IDDM have a wide range of renal structure, from within normal limits to advanced lesions that overlap those of patients who have high levels of MA and border on those seen in patients who have overt DN. Patients who have low-level MA have reduced glomerular structure similar to that of patients who have NA. Low GFR, hypertension, or both can occur in patients who have NA or low-level MA and are associated with more advanced lesions. Patients who have MA and AER greater than 45 mg/24 hr have more advanced lesions than do patients with NA or low-level MA, but similar lesions are present in these patients whether AER is greater than or less than 100 mg/24 hr. Increasing AER in NA and MA patients who have long-standing IDDM is associated with GBM and mesangial expansion. A structural basis for MA cannot currently be deduced from studies of glomerular epithelial cell fine structure, capillary wall charge site analysis, or immunohistochemical studies of renal ECM composition. Hemodynamic adaptations to mesangial expansion and reduced filtration surface and, perhaps, hydraulic conductivity may accelerate glomerular damage, as expressed by increasing AER. Microalbuminuria derives its clinical utility in IDDM, as it identifies a population of patients at statistically increased risk of progression to overt DN by acting as a marker of already well-established DN lesions. Although MA is currently the best of the widely used indicators of DN risk, it is not precise. Therapies that reduce MA may ultimately slow or prevent progression toward ESRD, but this finding requires confirmation by demonstrating that a given treatment strategy can preserve GFR.

Albuminuria↗
PubMed1985

Treatment of retinoblastoma by precision megavoltage radiation therapy.

The principal treatment concept in the Utrecht Retinoblastoma Centre is megavoltage irradiation, followed by light coagulation and/or cryotherapy if there is any doubt as to whether the residual tumour is still active. Radiation therapy is administered by means of a simple but highly accurate temporal beam technique. A standardized dose of 45 Gy is given in 15 fractions of 3 Gy at 3 fractions per week. From 1971 to 1982, 39 children with retinoblastoma have been irradiated in at least one eye. Of the 73 affected eyes, 18 were primarily enucleated, one received light coagulation only, and 54 received radiation therapy. Of the 54 irradiated eyes, 32 were additionally treated by light coagulation and/or cryotherapy for suspicious residual tumour (in 29 eyes), recurrent tumour (in 1 eye), and/or new tumour (in 3 eyes) and 10 were ultimately enucleated. Two eyes also received hyperthermia. The percentages of cure of the irradiated eyes with a minimum follow-up of 2 years were 100% (14/14), 100% (9/9), 83% (10/12), 79% (11/14) and 0% (0/5) in the Reese-Ellsworth groups I to V-A, respectively. Of the saved eyes 95% achieved useful vision. Eighteen eyes developed a clinically detectable radiation cataract; in five of these the lens was aspirated. Cataracts developed exclusively in those lenses of which a posterior portion of more than 1 mm had to be included in the treatment field. The likelihood and the degree of cataract formation was found to be directly related to the dose of radiation to the germinative zone of the lens epithelium. The minimum cataractogenic dose found in this series was 8 Gy.

Cataract↗
PubMed2004

Nasopharyngeal carcinoma treated with precision-oriented radiation therapy techniques including intensity-modulated radiotherapy: preliminary results.

This paper reports preliminary results with intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). Between August 2000 and May 2001, we treated 19 patients with NPC using IMRT. Twelve patients had stage I-II disease and seven had stage III-IV disease. Six patients received 9.0-19.8 Gy three-dimensional conformal radiotherapy (3D-CRT) before IMRT and 18 patients received a brachytherapy boost after IMRT. The mean follow-up time was 13.0 months. All patients with stage II-IV disease except one received two cycles of chemoradiotherapy with cisplatin and 5-fluorouracil (5-FU) during radiotherapy, followed by two to four cycles of chemotherapy after radiotherapy. Tumor response was assessed using clinical examination and computerized tomography or magnetic resonance imaging. The mean doses administered to the gross tumor volume and clinical tumor volume were 70.9 Gy and 63.2 Gy, respectively. The mean doses administered to the right and left parotid glands were 38.1 Gy and 38.6 Gy, respectively. All 19 patients had a complete response of primary and lymph node disease. Grade III mucositis developed during chemoradiotherapy in 15 patients (79%). In addition, clinical grade I xerostomia was recorded in nine patients, grade II in nine, and grade III in one. This study demonstrated that 3D-CRT, IMRT, intracavitary brachytherapy, and chemotherapy are effective and safe methods to treat NPC. Although IMRT treatment spared parotid gland function, its efficacy may be significantly influenced by disease stage and location of the neck lymph nodes. More cases and a longer follow-up to assess survival and complications are planned.

Adult↗
PubMed2026

Metagenome-scale modeling to assess microbiome metabolic complementarity for precision microbiota transplantation therapies.

Fecal microbiota transplantation (FMT) holds therapeutic promise beyond recurrent Clostridioides difficile infection, but clinical outcomes remain unpredictable and donor-selection strategies remain limited, in part because the role of donor&#x2012;recipient metabolic interactions in shaping the post-FMT community remains poorly understood. Here, we leverage metagenome-scale metabolic modeling to quantify metabolic niche complementarity between donor and recipient microbiomes and predict post-FMT community composition. Using MICOM-derived metabolic models, we show that donor genomes whose metabolic flux profiles are more dissimilar from the recipient community colonize at significantly higher rates in a murine FMT model. In a human IBS trial, the same metric predicted post-FMT community composition via leave-one-out cross-validation and captured known disease-associated alterations in short-chain fatty acid, sulfur, and gas metabolism. We then performed 2,548 in silico FMT simulations between IBS-D/M patients and donors from the OpenBiome biobank to evaluate personalized donor screening, identifying super-donors characterized by high taxonomic diversity, broad metabolic niche coverage, and community interaction networks dominated by cross-feeding rather than competition. Together, these results support metabolic niche complementarity as a potential determinant of post-FMT community composition and provide a mechanistic basis for evaluating donor-recipient metabolic compatibility. This framework offers a scalable approach for generating testable hypotheses for personalized donor selection.

Fecal Microbiota Transplantation↗
PubMed2005

A novel paradigm for therapeutic basis of advanced heart failure--assessment by gene therapy.

The precise mechanism(s) of the progression of advanced heart failure (HF) should be determined to establish strategies for its treatment or prevention. Based on pathological, molecular, and physiological findings in 3 animal models and human cases, we propose a novel scheme that a vicious cycle formed by increased sarcolemma (SL) permeability, preferential activation of calpain over calpastatin, and translocation and cleavage of dystrophin (Dys) commonly lead to advanced HF. The aim of this article was to assess our recent paradigm that disruption of myocardial Dys is a final common pathway to advanced HF, irrespective of its hereditary or acquired origin, but not intended to provide a comprehensive overview of the various factors that may be involved in the course of HF in different clinical settings. In addition, each component of Dys-associated proteins (DAP) was heterogeneously degraded in vivo and in vitro, i.e. Dys and alpha-sarcoglycan (SG) were markedly destroyed using isolated calpain 2, while delta-SG was not degraded at all. The up-regulation of calpain 2 was confirmed through previously published data that remain insufficient for precise evaluation, supporting our new scheme that the activation of calpain(s) is involved in the steady process of Dys cleavage. In addition, somatic gene therapy is discussed as a potential option to ameliorate the physiological/metabolic indices and to improve the prognosis.

Animals↗