scholarly journals Validation of a Lab-on-Chip Assay for Measuring Sorafenib Effectiveness on HCC Cell Proliferation

2021 ◽  
Vol 22 (23) ◽  
pp. 13090
Author(s):  
Emanuele Piccinno ◽  
Anna Grazia Monteduro ◽  
Francesco Dituri ◽  
Silvia Rizzato ◽  
Gianluigi Giannelli ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
New Drugs ◽  
Patient Specific ◽  
Disease Heterogeneity ◽  
Lab On Chip ◽  
Speed Up ◽  
On Chip ◽  
Proliferation Assays ◽  
Non Destructive

Hepatocellular carcinoma (HCC) is a highly lethal cancer, and although a few drugs are available for treatment, therapeutic effectiveness is still unsatisfactory. New drugs are urgently needed for hepatocellular carcinoma (HCC) patients. In this context, reliable preclinical assays are of paramount importance to screen the effectiveness of new drugs and, in particular, measure their effects on HCC cell proliferation. However, cell proliferation measurement is a time-consuming and operator-dependent procedure. The aim of this study was to validate an engineered miniaturized on-chip platform for real-time, non-destructive cell proliferation assays and drug screening. The effectiveness of Sorafenib, the first-line drug mainly used for patients with advanced HCC, was tested in parallel, comparing the gold standard 96-well-plate assay and our new lab-on-chip platform. Results from the lab-on-chip are consistent in intra-assay replicates and comparable to the output of standard crystal violet proliferation assays for assessing Sorafenib effectiveness on HCC cell proliferation. The miniaturized platform presents several advantages in terms of lesser reagents consumption, operator time, and costs, as well as overcoming a number of technical and operator-dependent pitfalls. Moreover, the number of cells required is lower, a relevant issue when primary cell cultures are used. In conclusion, the availability of inexpensive on-chip assays can speed up drug development, especially by using patient-derived samples to take into account disease heterogeneity and patient-specific characteristics.

scholarly journals Engineering Breast Cancer On-chip—Moving Toward Subtype Specific Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Carmen Moccia ◽  
Kristina Haase
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Triple Negative ◽  
New Drugs ◽  
Patient Specific ◽  
Preclinical Models ◽  
Cancer Subtypes ◽  
On Chip

Breast cancer is the second leading cause of death among women worldwide, and while hormone receptor positive subtypes have a clear and effective treatment strategy, other subtypes, such as triple negative breast cancers, do not. Development of new drugs, antibodies, or immune targets requires significant re-consideration of current preclinical models, which frequently fail to mimic the nuances of patient-specific breast cancer subtypes. Each subtype, together with the expression of different markers, genetic and epigenetic profiles, presents a unique tumor microenvironment, which promotes tumor development and progression. For this reason, personalized treatments targeting components of the tumor microenvironment have been proposed to mitigate breast cancer progression, particularly for aggressive triple negative subtypes. To-date, animal models remain the gold standard for examining new therapeutic targets; however, there is room for in vitro tools to bridge the biological gap with humans. Tumor-on-chip technologies allow for precise control and examination of the tumor microenvironment and may add to the toolbox of current preclinical models. These new models include key aspects of the tumor microenvironment (stroma, vasculature and immune cells) which have been employed to understand metastases, multi-organ interactions, and, importantly, to evaluate drug efficacy and toxicity in humanized physiologic systems. This review provides insight into advanced in vitro tumor models specific to breast cancer, and discusses their potential and limitations for use as future preclinical patient-specific tools.

scholarly journals Design, Synthesis, and Biological Evaluation of Pyrano[2,3-c]-pyrazole–Based RalA Inhibitors Against Hepatocellular Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuting Wang ◽  
Mingyao He ◽  
Xiang Li ◽  
Jinlong Chai ◽  
Qinglin Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Biological Evaluation ◽  
Small Gtpases ◽  
Pyrazole Derivatives ◽  
Design Synthesis ◽  
Tumor Progress ◽  
Proliferation Assays ◽  
Synthesis And Biological Evaluation

The activation of Ras small GTPases, including RalA and RalB, plays an important role in carcinogenesis, tumor progress, and metastasis. In the current study, we report the discovery of a series of 6-sulfonylamide-pyrano [2,3-c]-pyrazole derivatives as novel RalA inhibitors. ELISA-based biochemical assay results indicated that compounds 4k–4r suppressed RalA/B binding capacities to their substrates. Cellular proliferation assays indicated that these RalA inhibitors potently inhibited the proliferation of HCC cell lines, including HepG2, SMMC-7721, Hep3B, and Huh-7 cells. Among the evaluated compounds, 4p displayed good inhibitory capacities on RalA (IC50 = 0.22 μM) and HepG2 cells (IC50 = 2.28 μM). Overall, our results suggested that a novel small-molecule RalA inhibitor with a 6-sulfonylamide-pyrano [2, 3-c]-pyrazole scaffold suppressed autophagy and cell proliferation in hepatocellular carcinoma, and that it has potential for HCC-targeted therapy.

Multiprocessor transport surveillance video system based on "system on chip" technology

2020 ◽  
Author(s):  
Ш.С. Фахми ◽  
Н.В. Шаталова ◽  
В.В. Вислогузов ◽  
Е.В. Костикова
Keyword(s):  
System On Chip ◽  
Reference Points ◽  
Surveillance Video ◽  
Video Information ◽  
Chip Technology ◽  
Intelligent Video Surveillance System ◽  
Speed Up ◽  
Algorithmic Analysis ◽  
Computational Procedures ◽  
On Chip

В данной работе предлагаются математический аппарат и архитектура многопроцессорной транспортной системы на кристалле (МПТСнК). Выполнена программно-аппаратная реализация интеллектуальной системы видеонаблюдения на базе технологии «система на кристалле» и с использованием аппаратного ускорителя известного метода формирования опорных векторов. Архитектура включает в себя сложно-функциональные блоки анализа видеоинформации на базе параллельных алгоритмов нахождения опорных точек изображений и множества элементарных процессоров для выполнения сложных вычислительных процедур алгоритмов анализа с использованием средств проектирования на базе реконфигурируемой системы на кристалле, позволяющей оценить количество аппаратных ресурсов. Предлагаемая архитектура МПТСнК позволяет ускорить обработку и анализ видеоинформации при решении задач обнаружения и распознавания чрезвычайных ситуаций и подозрительных поведений. In this paper, we propose the mathematical apparatus and architecture of a multiprocessor transport system on a chip (MPTSoC). Software and hardware implementation of an intelligent video surveillance system based on the "system on chip" technology and using a hardware accelerator of the well-known method of forming reference vectors. The architecture includes complex functional blocks for analyzing video information based on parallel algorithms for finding image reference points and a set of elementary processors for performing complex computational procedures for algorithmic analysis. using design tools based on a reconfigurable system on chip that allows you to estimate the amount of hardware resources. The proposed MPTSoC architecture makes it possible to speed up the processing and analysis of video information when solving problems of detecting and recognizing emergencies and suspicious behaviors

Expression of β-Catenin in Hepatocellular Carcinoma

2001 ◽  
Vol 71 (3) ◽  
pp. 116-125
Author(s):  
Norina Basa ◽  
Daniela Lazar ◽  
Remus Cornea ◽  
Sorina Taban ◽  
Melania Ardelean ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Mitotic Index ◽  
Histological Grade ◽  
Proliferation Index ◽  
Tumor Cell Proliferation ◽  
Ki 67 ◽  
B Virus ◽  
Development And Evolution

Alteration of β-catenin expression is involved in the development and evolution of hepatocellular carcinoma (HCC); β-catenin is able to influence tumor cell proliferation. We analyzed the immunohistochemical (IHC) expression of β-catenin on a group of 32 patients diagnosed with HCC using the anti-β-catenin monoclonal antibody (clone E247). We correlated the expression of β-catenin with the proliferation index of Ki-67 (PI Ki-67), the mitotic index (MI) and other clinical and pathological features. We observed an altered β-catenin expression in 58.38% of all HCC cases. This expression was insignificantly correlated with tumor size (]5 cm) (p = 0.683), histological grade G1-G2 (p = 0.307), vascular invasion (p = 0.299) and advanced pT stage (p = 0.453); we obtained a significantly higher MI in HCC with altered β-catenin expression (p = 0.018), as compared to HCC without overexpression (1.66 � 1.37) (p = 0.038) and a PI Ki-67 of 22.49 � 20.1 and 28.24 � 18.2, respectively in tumors with altered β-catenin expression with insignificant differences compared to HCC without overexpression (25.95 � 15.2) (p = 0.682 and p = 0.731, respectively). According to the results we obtained, aberrant β-catenin expression in HCC was correlated with a high mitotic index, therefore playing an important role in tumor progression by stimulating tumor cell proliferation; non-nuclear β-catenin overexpression can have a pathological significance in HCC, especially in cases of HCC associated with hepatitis B virus (HBV) infection.

Phytosterols and Triterpenoids for Prevention and Treatment of Metabolic-related Liver Diseases and Hepatocellular Carcinoma

2019 ◽  
Vol 20 (3) ◽  
pp. 197-214 ◽  
Author(s):  
Isabel Sánchez-Crisóstomo ◽  
Eduardo Fernández-Martínez ◽  
Raquel Cariño-Cortés ◽  
Gabriel Betanzos-Cabrera ◽  
Rosa A. Bobadilla-Lugo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Anticancer Agents ◽  
Liver Diseases ◽  
Membrane Receptors ◽  
New Drugs ◽  
Sexual Hormones ◽  
Steroid Nucleus ◽  
Alcoholic Fatty Liver ◽  
Prevention And Treatment

Background: Liver ailments are among the leading causes of death; they originate from viral infections, chronic alcoholism, and autoimmune illnesses, which may chronically be precursors of cirrhosis; furthermore, metabolic syndrome may worsen those hepatopathies or cause Non-alcoholic Fatty Liver Disease (NAFLD) that may advance to non-alcoholic steatohepatitis (NASH). Cirrhosis is the late-stage liver disease and can proceed to hepatocellular carcinoma (HCC). Pharmacological treatment options for liver diseases, cirrhosis, and HCC, are limited, expensive, and not wholly effective. The use of medicinal herbs and functional foods is growing around the world as natural resources of bioactive compounds that would set the basis for the development of new drugs. Review and Conclusion: Plant and food-derived sterols and triterpenoids (TTP) possess antioxidant, metabolic-regulating, immunomodulatory, and anti-inflammatory activities, as well as they are recognized as anticancer agents, suggesting their application strongly as an alternative therapy in some chronic diseases. Thus, it is interesting to review current reports about them as hepatoprotective agents, but also because they structurally resemble cholesterol, sexual hormones, corticosteroids and bile acids due to the presence of the steroid nucleus, so they all can share pharmacological properties through activating nuclear and membrane receptors. Therefore, sterols and TTP appear as a feasible option for the prevention and treatment of chronic metabolic-related liver diseases, cirrhosis, and HCC.

scholarly journals A Lab‐On‐chip Tool for Rapid, Quantitative, and Stage‐selective Diagnosis of Malaria

2021 ◽  
pp. 2004101
Author(s):  
Marco Giacometti ◽  
Francesca Milesi ◽  
Pietro Lorenzo Coppadoro ◽  
Alberto Rizzo ◽  
Federico Fagiani ◽  
...  
Keyword(s):  
Lab On Chip ◽  
On Chip
Sign in / Sign up

Export Citation Format

Share Document