scholarly journals Preclinical Application of Conditional Reprogramming Culture System for Laryngeal and Hypopharyngeal Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Yanbo Dong ◽  
Jian Wang ◽  
Wei Ji ◽  
Mengzhu Zheng ◽  
Peng Wang ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Cell Model ◽  
Clinical Decision ◽  
Culture Technique ◽  
Hypopharyngeal Carcinoma ◽  
Molecular Characteristics ◽  
Cancer Therapies ◽  
Drug Responses ◽  
Personalized Cancer

Management of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) remains highly challenging due to highly variable therapeutic responses. By establishing an in vitro model for LHSCC based on conditional reprogramming (CR), a cell-culture technique, we aim to investigate its potential value on personalized cancer therapies. Herein, a panel of 28 human LHSCC CR cells were established from 50 tumor tissues using the CR method. They retained tumorigenic potential upon xenotransplantation and recapitulated molecular characteristics of LHSCC. Differential responses to anticancer drugs and radiotherapy were detected in vitro. CR cells could be transformed to xenograft and organoid, and they shared comparable drug responses. The clinical drug responses were consistent with in vitro drug responses. Collectively, the patient-derived CR cell model could promisingly be utilized in clinical decision-making and assisted in the selection of personalized therapies for LHSCC.

scholarly journals Establishment and Preclinical Application of Conditional Reprogramming Culture System for Laryngeal and Hypopharyngeal Carcinoma

2021 ◽  
Author(s):  
Yanbo DONG ◽  
Jian WANG ◽  
Wei JI ◽  
Mengzhu ZHENG ◽  
Peng WANG ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
Drug Testing ◽  
Clinical Decision Making ◽  
Cell Model ◽  
Clinical Decision ◽  
Culture Technique ◽  
Hypopharyngeal Carcinoma ◽  
Molecular Characteristics ◽  
Drug Responses

Abstract Purpose Management of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) remains highly challenging due to their anatomic location and highly variable therapeutic responses. We aim to establish a new in vitro model for LHSCC based on conditional reprogramming (CR), a novel cell-culture technique, and investigate its potential value on personalized cancer therapies. Methods Primary LHSCC cells were isolated from tumor specimens and cultured under CR conditions. The characteristics and malignant potential of cells were evaluated by histological staining, whole-exome sequencing and heterotransplantation. The responses of CR tumor cells to anticancer drugs and radiotherapy were tested using cell proliferation assay. CR cells could form xenografts and organoids, which were used for drug testing respectively. Clinical responses for certain patients were also compared with in vitro responses. Results A panel of 28 human LHSCC CR cells were established from 50 tumor tissues. They retain tumorigenic potential upon xenotransplantation and recapitulate molecular characteristics of LHSCC. Differential responses to anticancer drugs and radiotherapy were detected in vitro. CR cells can be transformed to xenograft and organoid, shared comparable drug responses. The clinical drug responses were consistent with in vitro drug responses. Conclusions The patient-derived CR cell model could promisingly be utilized in clinical decision-making and assist in the selection of personalized therapies for LHSCC.

scholarly journals Reducing complexity and unidentifiability when modelling human atrial cells

2020 ◽  
Vol 378 (2173) ◽  
pp. 20190339 ◽  
Author(s):  
C. Houston ◽  
B. Marchand ◽  
L. Engelbert ◽  
C. D. Cantwell
Keyword(s):  
Experimental Data ◽  
Clinical Decision Making ◽  
Cell Model ◽  
Sodium Current ◽  
Clinical Decision ◽  
Complex Model ◽  
Parameter Estimates ◽  
Gating Kinetics ◽  
Complex Formulation ◽  
Approximate Bayesian

Mathematical models of a cellular action potential (AP) in cardiac modelling have become increasingly complex, particularly in gating kinetics, which control the opening and closing of individual ion channel currents. As cardiac models advance towards use in personalized medicine to inform clinical decision-making, it is critical to understand the uncertainty hidden in parameter estimates from their calibration to experimental data. This study applies approximate Bayesian computation to re-calibrate the gating kinetics of four ion channels in two existing human atrial cell models to their original datasets, providing a measure of uncertainty and indication of potential issues with selecting a single unique value given the available experimental data. Two approaches are investigated to reduce the uncertainty present: re-calibrating the models to a more complete dataset and using a less complex formulation with fewer parameters to constrain. The re-calibrated models are inserted back into the full cell model to study the overall effect on the AP. The use of more complete datasets does not eliminate uncertainty present in parameter estimates. The less complex model, particularly for the fast sodium current, gave a better fit to experimental data alongside lower parameter uncertainty and improved computational speed. This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’.

scholarly journals Dantrolene in the treatment of MDMA-related hyperpyrexia: a systematic review

CJEM ◽  
2010 ◽  
Vol 12 (05) ◽  
pp. 435-442 ◽  
Author(s):  
Brian E. Grunau ◽  
Matthew O. Wiens ◽  
Jeffrey R. Brubacher
Keyword(s):  
Systematic Review ◽  
Clinical Decision Making ◽  
Case Reports ◽  
Data Extraction ◽  
Patient Characteristics ◽  
Clinical Decision ◽  
Poison Control ◽  
Published Data ◽  
Published Evidence

ABSTRACTObjective:The use of dantrolene in the treatment of hyperpyrexia related to MDMA (3,4-methylenedioxymethamphetamine) is controversial, with little data available to guide clinical decision-making. Although the treatment is recommended by several poison control centres, published data are primarily in the form of case reports and animal and in vitro experiments. We conducted a systematic review to investigate the published evidence regarding the safety and benefits of dantrolene for MDMA-related hyperpyrexia in humans.Data sources:A systematic search of Embase and MEDLINE was conducted from the earliest possible date to November 2008.Study selection:All human trials and case reports of MDMA-related hyperpyrexia were considered.Data extraction:Data were abstracted systematically and characteristics including use of dantrolene, adverse reactions attributed to dantrolene, peak temperature, complications from MDMA-related hyperpyrexia and survival were recorded.Data synthesis:Our search yielded 668 articles of which 53, reporting 71 cases of MDMA-induced hyperpyrexia, met our inclusion criteria. No clinical trials, randomized controlled trials, observational studies or meta-analyses were identified. Dantrolene was used in 26 cases. Patient characteristics were similar in the dantrolene and no dantrolene groups. The proportion of survivors was higher in the dantrolene group (21/26) than in the no dantrolene group (25/45). This difference was especially pronounced in those with extreme (≥ 42°C) and severe (≥ 40°C) fever, with a survival rate of 8 of 13 and 10 of 10, respectively, in the dantrolene group compared with 0 of 4 and 15 of 27 in the no dantrolene group. There were no reports of adverse events attributable to dantrolene with the exception of a possible association with an episode of transient hypoglycemia.Conclusion:Our systematic review suggests that dantrolene is safe for patients with MDMA-related hyperpyrexia. Dantrolene may also be associated with improved survival and reduced complications, especially in patients with extreme (≥ 42°C) or severe (≥ 40°C) hyperpyrexia, although this conclusion must be interpreted with caution given the risk of reporting or publication bias.

THE VALUE OF IN VITRO DIAGNOSTIC TESTING IN THE PROVISION OF MEDICAL CARE TO ELDERLY PATIENTS WITH CARDIOVASCULAR DISEASES

2020 ◽  
Vol 65 (3) ◽  
pp. 191-196
Author(s):  
A. S. Pushkin ◽  
O. V. Lyang ◽  
T. A. Ahmedov ◽  
S. A. Rukavishnikova
Keyword(s):  
Decision Making ◽  
Medical Care ◽  
Laboratory Tests ◽  
Clinical Decision Making ◽  
Diagnostic Testing ◽  
Clinical Decision ◽  
Initial Examination ◽  
Attending Physicians ◽  
The Impact

In vitro diagnostics are used at all stages of patient care. The aim of this study was to assess the impact of laboratory examination on clinical decision-making in providing medical care to patients with a cardiovascular profile. We also took into account the level of financing for the laboratory industry in the Russian Federation. We divided our study on three sequential steps: literature review, survey of clinicians and test-survey of clinicians. The share of costs for the laboratory tests in 2017 amounted to about 8% of the total funding for Russian health care. About 80% (70; 90) of the visits of the attending physicians are associated with the appointment of laboratory tests. Among patients who were prescribed any laboratory test - in 62.1% (95% CI 16.9-24.9) cases, the results of these tests influenced clinical decision making related to the initiation, modification or termination of any treatment. All visits of clinicians were divided by purpose: tests were prescribed in almost 100% (90; 100) cases during the initial examination, in 40% (20; 60) cases during repeated visits, and in 40% (15; 40) cases when patients were examined before discharge. In more than half of cases (57,4%; n=31), doctors correctly assumed about the about the share of financing of the laboratory industry. The majority of respondents considered the amount of expenses adequate and recommended to maintain the current level in the future. According to attending physicians, new laboratory markers should demonstrate additional information about clinical relevance to improve patient outcomes. Thus, in current economic realities, future laboratory tests should be financially maximally available and at the same time be clinically highly effective auxiliary instruments. It creates new challenges in finding laboratory biomarkers and putting them into clinical practice.

scholarly journals A New Device to Automate the Monitoring of Critical Patients’ Urine Output

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Abraham Otero ◽  
Andrey Apalkov ◽  
Roemi Fernández ◽  
Manuel Armada
Keyword(s):  
Patient Outcomes ◽  
Urine Output ◽  
Clinical Decision Making ◽  
Capacitive Sensor ◽  
Clinical Decision ◽  
In Vitro Tests ◽  
Therapeutic Goals ◽  
New Device ◽  
Improve Patient

Urine output (UO) is usually measured manually each hour in acutely ill patients. This task consumes a substantial amount of time. Furthermore, in the literature there is evidence that more frequent (minute-by-minute) UO measurement could impact clinical decision making and improve patient outcomes. However, it is not feasible to manually take minute-by-minute UO measurements. A device capable of automatically monitoring UO could save precious time of the healthcare staff and improve patient outcomes through a more precise and continuous monitoring of this parameter. This paper presents a device capable of automatically monitoring UO. It provides minute by minute measures and it can generate alarms that warn of deviations from therapeutic goals. It uses a capacitive sensor for the measurement of the UO collected within a rigid container. When the container is full, it automatically empties without requiring any internal or external power supply or any intervention by the nursing staff. In vitro tests have been conducted to verify the proper operation and accuracy in the measures of the device. These tests confirm the viability of the device to automate the monitoring of UO.

scholarly journals Feasibility study of in vitro drug sensitivity assay of advanced non-small cell lung adenocarcinomas

2020 ◽  
Vol 7 (1) ◽  
pp. e000505
Author(s):  
Emoke Papp ◽  
Anita Steib ◽  
Elhusseiny MM Abdelwahab ◽  
Judit Meggyes-Rapp ◽  
Laszlo Jakab ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Therapy Response ◽  
Clinical Decision ◽  
Response To Therapy ◽  
Solid Tumours ◽  
Chemosensitivity Test ◽  
Pleural Effusions ◽  
In Vitro Chemosensitivity ◽  
Lung Adenocarcinomas

Background Despite improved screening techniques, diagnosis of lung cancer is often late and its prognosis is poor. In the present study, in vitro chemosensitivity of solid tumours and pleural effusions of lung adenocarcinomas were analysed and compared with clinical drug response.Methods Tumour cells were isolated from resected solid tumours or pleural effusions, and cryopreserved. Three-dimensional (3D) tissue aggregate cultures were set up when the oncoteam reached therapy decision for individual patients. The aggregates were then treated with the selected drug or drug combination and in vitro chemosensitivity was tested individually measuring ATP levels. The clinical response to therapy was assessed by standard clinical evaluation over an 18 months period.Results Based on the data, the in vitro chemosensitivity test results correlate well with clinical treatment response.Conclusions Such tests if implemented into the clinical decision making process might allow the selection of an even more individualised chemotherapy protocol which could lead to better therapy response.

scholarly journals DruID: Personalized Drug Recommendations by Integrating Multiple Biomedical Databases for Cancer

2021 ◽  
Author(s):  
Herty Liany ◽  
Anand Jeyasekharan ◽  
Vaibhav Rajan
Keyword(s):  
Cancer Progression ◽  
Clinical Decision Making ◽  
Cancer Cell Line ◽  
Drug Efficacy ◽  
Clinical Decision ◽  
Sequencing Technologies ◽  
Effective Therapeutic Strategy ◽  
Algorithmic Framework ◽  
Combine Drug

Advances in next-generation sequencing technologies have led to the development of personalized genomic profiles in diagnostic panels that inform oncologists of alterations in clinically relevant genes. While targeted therapies for some alterations may be found, an effective therapeutic strategy should consider multiple and dependent genetic interactions that affect cancer progression, a task which remains challenging. There are ongoing efforts to profile cancer cells in-vitro, both to catalog their genomic information and study their sensitivity to various drugs. There is a need for tools that can interpret the personalized genomic profile of a patient in light of information from these biological and pre-clinical studies and recommend potentially useful drugs. To address this need, we develop a new algorithmic framework called DruID, to effectively combine drug efficacy predictions from a deep neural network model with information, such as drug sensitivity, drug-drug interactions and genetic dependencies, from multiple publicly available databases. We empirically evaluate DruID on cancer cell line data on which efficacy of many drugs have been experimentally determined. We find that DruID outperforms competing approaches and promises to be a useful tool in clinical decision-making.

scholarly journals Contribution of non-coding mutations to RPGRIP1-mediated inherited retinal degeneration

2017 ◽  
Author(s):  
Farzad Jamshidi ◽  
Emily M. Place ◽  
Sudeep Mehrotra ◽  
Daniel Navarro-Gomez ◽  
Mathew Maher ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Amplicon Sequencing ◽  
Genetic Diagnostics ◽  
Loss Of Function ◽  
Gene Therapies ◽  
Retinal Degenerations ◽  
Whole Exome

AbstractPurposeWith the advent of gene therapies for inherited retinal degenerations (IRDs), genetic diagnostics will have an increasing role in clinical decision-making. Yet the genetic cause of disease cannot be identified using exon-based sequencing for a significant portion of patients. We hypothesized that non-coding mutations contribute significantly to the genetic causality of IRDs and evaluated patients with single coding mutations in RPGRIP1 to test this hypothesis.MethodsIRD families underwent targeted panel sequencing. Unsolved cases were explored by whole exome and genome sequencing looking for additional mutations. Candidate mutations were then validated by Sanger sequencing, quantitative PCR, and in vitro splicing assays in two cell lines analyzed through amplicon sequencing.ResultsAmong 1722 families, three had biallelic loss of function mutations in RPGRIP1 while seven had a single disruptive coding mutation. Whole exome and genome sequencing revealed potential non-coding mutations in these seven families. In six, the non-coding mutations were shown to lead to loss of function in vitro.ConclusionNon-coding mutations were identified in 6 of 7 families with single coding mutations in RPGRIP1. The results suggest that non-coding mutations contribute significantly to the genetic causality of IRDs and RPGRIP1–mediated IRDs are more common than previously thought.

scholarly journals A Novel Six Metastasis-Related Prognostic Gene Signature for Patients With Osteosarcoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Di Zheng ◽  
Kezhou Xia ◽  
Ling Yu ◽  
Changtian Gong ◽  
Yubo Shi ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Epithelial To Mesenchymal Transition ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Gene Signature ◽  
Suppressor Gene ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Osteosarcoma is the most common malignant bone tumor, and although there has been significant progress in its management, metastases often herald incurable disease. Here we defined genes differentially expressed between primary and metastatic osteosarcoma as metastasis-related genes (MRGs) and used them to construct a novel six-MRG prognostic signature for overall survival of patients with osteosarcoma. Validation in internal and external datasets confirmed satisfactory accuracy and generalizability of the prognostic model, and a nomogram based on the signature and clinical variables was constructed to aid clinical decision-making. Of the six MRGs, FHIT is a well-documented tumor suppressor gene that is poorly defined in osteosarcoma. Consistent with tumor suppressor function, FHIT was downregulated in osteosarcoma cells and human osteosarcoma samples. FHIT overexpression inhibited osteosarcoma proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, FHIT overexpression upregulate the epithelial marker E-cadherin while repressing the mesenchymal markers N-cadherin and vimentin. Our six-MRG signature represents a novel and clinically useful prognostic biomarker for patients with osteosarcoma, and FHIT might represent a therapeutic target by reversing epithelial to mesenchymal transition.

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