Cervical Evaluation: From Ancient Medicine to Precision Medicine.
Ontology highlight
ABSTRACT:
SUBMITTER: Feltovich H
PROVIDER: S-EPMC5503468 | biostudies-literature | 2017 Jul
REPOSITORIES: biostudies-literature
Publications
Cervical Evaluation: From Ancient Medicine to Precision Medicine.
Obstetrics and gynecology 20170701 1
Since ancient times, cervical assessment for predicting timing of delivery has relied primarily on digital (subjective) assessment of dilatation, softening, and length. To date, transvaginal ultrasound cervical length is the only one of these parameters that meets criteria for a biomarker; no objective, quantitative measure of cervical dilatation or softening has gained clinical acceptance. This review discusses how the cervix has been assessed from ancient times to the present day and how a pre ...[more]
Similar Datasets
Project description:Purpose of ReviewPrecision medicine (PM) represents a new paradigm in disease diagnosis, prevention, and treatment. The PM approach focuses on the characterization of different phenotypes and pathogenic pathways in order to allow the selection of specific biomarkers that will be useful in disease management. Rhinitis is a highly prevalent and heterogeneous disease, both in terms of underlying endotypes and clinical presentations. Therefore, to apply the PM principles to the various rhinitis subtypes rise as a meaningful strategy to improve evaluation and treatment.Recent FindingsThe technology of recombinant allergens has allowed molecular characterization of IgE reactivity of specific individual components of allergenic extracts. Recently published and ongoing clinical trials based on component resolved diagnosis (CRD) bring more precision to allergen immunotherapy for allergic rhinitis. Monoclonal antibodies against various cytokines involved in inflammatory allergic and nonallergic rhinitis endotypes show promissory results.SummaryBetter understanding of pathogenic pathways together with an accurate phenotype classification of patients presented with rhinitis symptoms contributes to point out clinical usefulness of biomarkers and other diagnostic tools, which leads to more accurate environmental control measures, personalized pharmacologic options, and new biological therapy developments.
| S-EPMC7099688 | biostudies-literature
Project description:Project Description
Esophagitis is a frequent, but at the molecular level poorly characterized condition with diverse underlying etiologies and treatments. Correct diagnosis can be challenging due to partially overlapping histological features. By proteomic profiling of 55 biopsy specimens representing controls, Reflux- (GERD), Eosinophilic-(EoE), Crohns-(CD), and Herpes simplex (HSV)-esophagitis, as well as Candida albicans infection by LC-MS/MS, we identified distinct signatures and functional networks. Our integrated AI-assisted morphoproteomic approach allows deeper insights in disease-specific molecular alterations and represents a promising tool in esophagitis-related precision medicine.
The FFPE samples were further processed including macrodissection, protein extraction, protein precipitation, protein digestion, and peptide clean up according to a previously published and modified protocol (Buczak et al., 2020). For further details, please refer to the Materials and Methods section of the manuscript.
In depth proteomic characterization of the samples a label free high-resolution LC-MS/MS approach using an Orbitrap Tribrid Fusion mass spectrometer was chosen (operated in DIA mode). Tryptic peptides were loaded onto a µPAC Trapping Column with a pillar diameter of 5 µm, inter-pillar distance of 2.5 µm, pillar length/bed depth of 18 µm, external porosity of 9%, bed channel width of 2 mm and length of 10 mm; pillars are superficially porous with a porous shell thickness of 300 nm and pore sizes in the order of 100 to 200 Å at a flow rate of 10 µl per min in 0.1% trifluoroacetic acid in HPLC-grade water. Peptides were eluted and separated on the PharmaFluidics µPAC nano-LC column: 50 cm µPAC C18 with a pillar diameter of 5 µm, inter-pillar distance of 2.5 µm, pillar length/bed depth of 18 µm, external porosity of 59%, bed channel width of 315 µm and bed length of 50 cm; pillars are superficially porous with a porous shell thickness of 300 nm and pore sizes in the order of 100 to 200 Å by a linear gradient from 2% to 30 % of buffer B (80% acetonitrile and 0.08% formic acid in HPLC-grade water) in buffer A (2% acetonitrile and 0.1% formic acid in HPLC-grade water) at a flow rate of 300 nl per min. The remaining peptides were eluted by a short gradient of 10 minutes from 30% to 95% buffer B; followed by 25 minutes at 2% of buffer B, the total gradient run was 120 min.
Spectra were acquired in DIA mode using 50 variable-width windows over the mass range 350-1500 m/z. The Orbitrap was used for MS1 and MS2 detection, with an AGC target for MS1 set to 20x104 and a maximum injection time to 100 ms. MS2 scan range was set between 200 and 2000 m/z, with a minimum of 6 points across the peak. Orbitrap resolution for MS2 was set to 30K, isolation window set to 1.6, AGC target to 50x104 and maximum injection time to 54 ms. MS1 and MS2 data were acquired in centroid mode.
In order to check for retention time (RT) stability, iRT standards (Biognosys) were spiked in each sample according to the manufacturer recommendations, the 11 iRT peptide sequences were manually added to the database and used during DIA-NN search to generate the precursor ion library used for MS data analysis. To reduce the possibility of carry over and cross contamination between the samples, two BSA washes were used between samples, and a trap column wash followed by 2 BSA washes was used every 10 samples sequence.
The above-mentioned workflow is schematically displayed in Fig. 1B.
LC-MS/MS was performed at the Proteome Center Tuebingen (PCT). Here, 250 ng of peptides were loaded onto an Easy-nLC 1200 system coupled to a quadrupole Orbitrap Exploris 480 mass spectrometer (all Thermo Fisher Scientific, Waltham, MA, USA) as previously described (Krauss et al, 2023).
MS raw data files were analyzed using DIA-NN 1.8.1 (Demichev et al, 2020) in library-free mode against the human database (UniProt release March 2024, 20412 proteins). First, a precursor ion library was generated using FASTA digest for library-free search in combination with deep learning-based spectra prediction. An experimental library generated from the DIA-NN search was used for cross-run normalization and mass accuracy correction. Only high-accuracy spectra with a minimum precursor FDR of 0.01, and only tryptic peptides (2 missed Tryptic cleavages) were used for protein quantification. The match between runs option was activated and no shared spectra were used for protein identification. Similarly, Normal, HSV, and Candida samples were searched against reviewed entries of HSV1 (taxonomy id 10298, 125 entries), HSV2 (taxonomy id 10310, 95 entries), and C. albicans (taxonomy id 5476, 1412 entries) downloaded on 04.03.2024, in addition to the human database.
2024-06-10 | MSV000094966 | MassIVE
Project description:Cervical cancer (CC) is -second to breast cancer- a dominant cause of gynecological cancer-related deaths worldwide. CC tumor biopsies and blood samples are of easy access and vital for the development of future precision medicine strategies.BIO-RAIDs is a prospective multicenter European study, presently recruiting patients in 6 EU countries. Tumor and liquid biopsies from patients with previously non-treated cervical cancer (stages IB2-IV) are collected at defined time points. Patients receive standard primary treatment according to the stage of their disease. 700 patients are planned to be enrolled. The main objectives are the discovery of -dominant molecular alterations, -signalling pathway activation, and -tumor micro-environment patterns that may predict response or resistance to treatment. An exhaustive molecular analysis is performed using 1° Next generation sequencing, 2° Reverse phase protein arrays and 3° Immuno-histochemistry.The clinical study BIO-RAIDs is activated in all planned countries, 170 patients have been recruited till now. This study will make an important contribution towards precision medicine treatments in cervical cancer. The results will support the development of clinical practice guidelines for cervical cancer patients to improve their prognosis and their quality of life.Clinicaltrials.gov: NCT02428842 , registered 10 February 2015.
| S-EPMC4632364 | biostudies-literature
Project description:The development of precision medicine strategies requires prior knowledge of the genetic background of the target population. However, despite the availability of data from admixed Americans within large reference population databases, we cannot use these data as a surrogate for that of the Brazilian population. This lack of transferability is mainly due to differences between ancestry proportions of Brazilian and other admixed American populations. To address the issue, a coalition of research centres created the Brazilian Initiative on Precision Medicine (BIPMed), an initiative of five Research Innovation and Dissemination Centers (RIDCs) supported by FAPESP.
2020-08-22 | GSE156652 | GEO
Project description:Recent advances in biotechnology and cancer genomics have afforded enormous opportunities for development of more effective anticancer therapies. A key thrust of this modern drug development paradigm is successful identification of predictive biomarkers that can distinguish patients who might be sensitive to new targeted therapies. To respond to this challenge, a number of phase III cancer trial designs integrating biomarker-based objectives have been proposed and implemented in oncology drug development. In this article, we provide an updated review of commonly used biomarker-based randomized clinical trial designs, with a particular focus on design efficiency. When the efficacy of a new therapy may be limited to a biomarker-defined subgroup, the choice of an appropriate randomized clinical trial design should be guided by the strength of the biomarker's credentials. If compelling evidence indicates that a targeted therapy is beneficial only in a particular biomarker-defined subgroup, an enrichment design should be used. If there is strong evidence that the treatment is likely to be more beneficial in the biomarker-positive patients but a meaningful benefit is also possible in the biomarker-negative patients, then a properly powered biomarker-stratified design (eg, a subgroup-specific or Marker Sequential Test strategy) would provide the most rigorous determination of the sensitive populations. If the evidence supporting the predictive value of the biomarker is weak and the treatment is expected to work in the overall population, then a fallback design could be used. Careful selection of an appropriate phase III design strategy that integrates evaluation of a new anticancer therapy and its companion diagnostic is critical to the success of precision medicine in oncology.
| S-EPMC7446320 | biostudies-literature
Project description:Cholangiocarcinoma is one of the epithelial cancers with the poorest prognosis and the narrowest therapeutic choice in humans. Compared with other cancer types, cholangiocarcinoma has been often neglected by oncology and liver research studies, thereby leaving many issues unsolved. Apart from the early and marked aggressiveness, one of the main reasons of the still unsatisfying clinical management of cholangiocarcinoma is its wide tumor heterogeneity needing more than other diseases a 'precision medicine' approach. In this regard, in the last few years there has been an awakening of interest aimed at dissecting the complex molecular and genomic profile of cholangiocarcinoma. Thus, a range of molecular players have been recently identified as putative mechanistic determinants of cholangiocarcinoma invasiveness, encompassing tyrosine kinase receptors, metabolic enzymes, transcription factors, small GTPases, ubiquitin ligases, and chromatin-remodelling proteins, whose aberrant expression may derive from stochastic mutations as well as from pro-oncogenic paracrine signals released by the stromal microenvironment, which is particularly exuberant in cholangiocarcinoma. Herein, we sought to overview the most relevant observations unravelling the genomic landscape of cholangiocarcinoma, and the prognostic and predictive biomarkers that consequently have been emerging. Then, we will discuss innovative treatment approaches derived from conventional chemotherapy, targeted therapies, antiangiogenic therapies and immunotherapy, and how they are opening new avenues towards a precision medicine in cholangiocarcinoma.
| S-EPMC6087799 | biostudies-literature
Project description:Bronchiectasis, due to its highly heterogenous nature, requires an individualised approach to therapy. Patients experience symptoms and exacerbations driven by a combination of impaired mucociliary clearance, airway inflammation and airway infection. Treatment of bronchiectasis aims to enhance airway clearance and to address the underlying causes of inflammation and infection susceptibility. Bronchiectasis has multiple causes and so the pathophysiology leading to individual symptoms and exacerbations are different between individuals. Standardised investigations are recommended by international guidelines to identify the underlying causes of bronchiectasis. The process of identifying the underlying biology within an individual is called "endotyping" and is an emerging concept across chronic diseases. Endotypes that have a specific treatment are referred to as "treatable traits" and a treatable traits approach to managing patients with bronchiectasis in a holistic and evidence-based manner is the key to improved outcomes. Bronchiectasis is an area of intense research. Endotyping allows identification of subsets of patients to allow medicines to be tested differently in the future where trials, rather than trying to achieve a "one size fits all" solution, can test efficacy in subsets of patients where the treatment is most likely to be efficacious.
| S-EPMC8753699 | biostudies-literature
Project description:Outcome in treatment of childhood cancers has improved dramatically since the 1970s. This success was largely achieved by the implementation of cooperative clinical research trial groups that standardized and developed treatment of childhood cancer. Nevertheless, outcome in certain types of malignancies is still unfavorable. Intensification of conventional chemotherapy and radiotherapy improved outcome only marginally at the cost of acute and long-term side effects. Hence, it is necessary to develop targeted therapy strategies.Here, we review the developments and perspectives in precision medicine in pediatric oncology with a special focus on targeted drug therapies like kinase inhibitors and inducers of apoptosis, the impact of cancer genome sequencing and immunotherapy.
| S-EPMC6119176 | biostudies-other
Project description:The pathogenesis of Cushing's disease is poorly understood; two recent reports identifying somatic mutations in USP8 in pituitary corticotroph tumors provide exciting advances in this field. These mutations alter EGFR trafficking and signaling, raising the prospect that EGFR inhibitors may move the treatment of this disease into the era of precision medicine.
| S-EPMC4456621 | biostudies-other
Project description:Frontotemporal dementia (FTD) is a common young-onset dementia presenting with heterogeneous and distinct syndromes. It is characterized by progressive deficits in behavior, language, and executive function. The disease may exhibit similar characteristics to many psychiatric disorders owing to its prominent behavioral features. The concept of precision medicine has recently emerged, and it involves neurodegenerative disease treatment that is personalized to match an individual's specific pattern of neuroimaging, neuropathology, and genetic variability. In this paper, the pathophysiology underlying FTD, which is characterized by the selective degeneration of the frontal and temporal cortices, is reviewed. We also discuss recent advancements in FTD research from the perspectives of clinical, imaging, molecular characterizations, and treatment. This review focuses on the approach of precision medicine to manage the clinical and biological complexities of FTD.
| S-EPMC6393374 | biostudies-other