Machine learning (ML) methods still have limited applicability in personalized oncology due to low numbers of available clinically annotated molecular profiles. This doesn't allow sufficient training of ML classifiers that could be used for improving molecular diagnostics.
We reviewed published datasets of high throughput gene expression profiles corresponding to cancer patients with known responses on chemotherapy treatments. We browsed Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Tumor Alterations Relevant for GEnomics-driven Therapy (TARGET) repositories.
We identified data collections suitable to build ML models for predicting responses on certain chemotherapeutic schemes. We identified 26 datasets, ranging from 41 till 508 cases per dataset. All the datasets identified were checked for ML applicability and robustness with leave-one-out cross validation. Twenty-three datasets were found suitable for using ML that had balanced numbers of treatment responder and non-responder caseortezomib, vincristine, trastuzumab, letrozole, tipifarnib, temozolomide, busulfan and cyclophosphamide.
Carotid and vagal paragangliomas (CPGLs and VPGLs) are rare neoplasms that arise from the paraganglia located at the bifurcation of carotid arteries and vagal trunk, respectively. Both tumors can occur jointly as multiple paragangliomas accounting for approximately 10 to 20% of all head and neck paragangliomas. However, molecular and genetic mechanisms underlying the pathogenesis of multiple paragangliomas remain elusive.
We report a case of multiple paragangliomas in a patient, manifesting as bilateral CPGL and unilateral VPGL. Tumors were revealed via computed tomography and ultrasound study and were resected in two subsequent surgeries. Both CPGLs and VPGL were subjected to immunostaining for succinate dehydrogenase (SDH) subunits and exome analysis. A likely pathogenic germline variant in the SDHD gene was indicated, while likely pathogenic somatic variants differed among the tumors.
The identified germline variant in the SDHD gene seems to be a driver in the development of multiple paragangliomas. However, different spectra of somatic variants identified in each tumor indicate individual molecular mechanisms underlying their pathogenesis.
The identified germline variant in the SDHD gene seems to be a driver in the development of multiple paragangliomas. However, different spectra of somatic variants identified in each tumor indicate individual molecular mechanisms underlying their pathogenesis.
Data are limited on whether TyG index is an independent predictor of arterial stiffness in hypertensive patients. The purpose of this study was to assess the association between the TyG index and arterial stiffness, and examined whether there were effect modifiers, in hypertensive patients.
This study included 4718 hypertensive adults, a subset of the China H-type Hypertension Registry Study. The TyG index was calculated as ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Arterial stiffness was determined by measuring brachial-ankle pulse wave velocity (baPWV).
The overall mean TyG index was 8.84. see more Multivariate linear regression analyses showed that TyG index was independently and positively associated with baPWV (β, 1.02; 95% confidence interval [CI] 0.83, 1.20). Consistently, Multiple logistic analyses showed a positive association between TyG index risk of elevated baPWV (> 75th percentile) (odds ratio [OR], 2.12; 95% CI 1.80, 2.50). Analyses using restricted cubic spline confirmed that the associations of TyG index with baPWV and elevated baPWV were linear. Subgroup analyses showed that stronger associations between TyG index and baPWV were detected in men (all P for interaction < 0.05).
TyG index was independently and positively associated with baPWV and elevated baPWV among hypertensive patients, especially in men. The data suggest that TyG index may serve as a simple and effective tool for arterial stiffness risk assessment in daily clinical practice.
TyG index was independently and positively associated with baPWV and elevated baPWV among hypertensive patients, especially in men. The data suggest that TyG index may serve as a simple and effective tool for arterial stiffness risk assessment in daily clinical practice.
Alzheimer's disease (AD) is the most common cause of dementia in the elderly, characterized by a progressive and irreversible loss of memory and cognitive abilities. Currently, the prevention and treatment of AD still remains a huge challenge. As a traditional Chinese medicine (TCM) prescription, Danggui-Shaoyao-san decoction (DSS) has been demonstrated to be effective for alleviating AD symptoms in animal experiments and clinical applications. However, due to the complex components and biological actions, its underlying molecular mechanism and effective substances are not yet fully elucidated.
In this study, we firstly systematically reviewed and summarized the molecular effects of DSS against AD based on current literatures of in vivo studies. Furthermore, an integrated systems pharmacology framework was proposed to explore the novel anti-AD mechanisms of DSS and identify the main active components. We further developed a network-based predictive model for identifying the active anti-AD components of DScomplex TCM prescription.
Overall, this study proposed an integrative systems pharmacology approach to disclose the therapeutic mechanisms of DSS against AD, which also provides novel in silico paradigm for investigating the effective substances of complex TCM prescription.
Targeted contrast nanoparticles for breast tumor imaging facilitates early detection and improves treatment efficacy of breast cancer. This manuscript reports the development of an epidermal growth factor receptor-2 (HER-2) specific, bi-modal, dendrimer conjugate to enhance computed tomography (CT) and magnetic resonance imaging (MRI) of HER-2-positive breast cancer. This material employs generation 5 poly(amidoamine) dendrimers, encapsulated gold nanoparticles, chelated gadolinium, and anti-human HER-2 antibody to produce the nanoparticle contrast agent.
Testing in two mouse tumor models confirms this contrast agent's ability to image HER-2 positive tumors. Intravenous injection of this nanoparticle in mice bearing HER-2 positive mammary tumors significantly enhances MRI signal intensity by ~ 20% and improves CT resolution and contrast by two-fold. Results by flow cytometry and confocal microscopy validate the specific targeting of the conjugate and its internalization in human HER-2 positive cells.
These results demonstrate that this nanoparticle conjugate can efficiently target and image HER-2 positive tumors in vivo and provide a basis for the development of this diagnostic tool for early detection, metastatic assessment and therapeutic monitoring of HER-2 positive cancers.see more
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