scholarly journals High-throughput tuning of ovarian cancer spheroids for on-chip invasion assays

2021 ◽  
Author(s):  
Changchong Chen ◽  
Yong He ◽  
Elliot Lopez ◽  
Franck Carreiras ◽  
Ayako Yamada ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Cancer Drug ◽  
Type I ◽  
Anti Cancer ◽  
Cancer Types ◽  
Tumor Modeling ◽  
On Chip ◽  
Cancer Spheroids ◽  
Number Of Cells ◽  
Invasion Assays

We developed an invasion assay by using microfabricated culture devices. First, ovarian tumor spheroids were generated with a culture patch device consisting of an agarose membrane formed with a honeycomb microframe, the patch, and gelatin nanofiber backbone. By changing the dimensions of the honeycomb compartments we were able to control the number of cells and size of the spheroids. When the spheroids were placed on a patch coated with a thin membrane of fibrillary type I collagen, spheroid disruption was observed due to substrate induced cell migration. This process is straightforward and should be applicable to other cancer types, as well as assays under microfluidic conditions, thereby holding the potential for use in tumor modeling and anti-cancer drug development.

scholarly journals An Anti-Cancer Drug Candidate CYC116 Suppresses Type I Hypersensitive Immune Responses through the Inhibition of Fyn Kinase in Mast Cells

2019 ◽  
Vol 27 (3) ◽  
pp. 311-317 ◽  
Author(s):  
Young Hwan Park ◽  
Hyun Woo Kim ◽  
Hyuk Soon Kim ◽  
Seung Taek Nam ◽  
Dajeong Lee ◽  
...  
Keyword(s):  
Mast Cells ◽  
Immune Responses ◽  
Cancer Drug ◽  
Drug Candidate ◽  
Type I ◽  
Fyn Kinase ◽  
Anti Cancer

scholarly journals Counteracting Cisplatin-Induced Testicular Damages by Natural Polyphenol Constituent Honokiol

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 723
Author(s):  
Tse-En Wang ◽  
Yu-Hua Lai ◽  
Kai-Chien Yang ◽  
Sung-Jan Lin ◽  
Chih-Lin Chen ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Type I ◽  
Dna Breaks ◽  
Gene Expressions ◽  
Beneficial Effects ◽  
Polyphenol Compound ◽  
Anti Cancer ◽  
Natural Polyphenol

Cisplatin, despite its anti-cancer ability, exhibits severe testicular toxicities when applied systemically. Due to its wide application in cancer treatment, reduction of its damages to normal tissue is an imminent clinical need. Here we evaluated the effects of honokiol, a natural lipophilic polyphenol compound, on cisplatin-induced testicular injury. We showed in-vitro and in-vivo that nanosome-encapsulated honokiol attenuated cisplatin-induced DNA oxidative stress by suppressing intracellular reactive oxygen species production and elevating gene expressions of mitochondrial antioxidation enzymes. Nanosome honokiol also mitigated endoplasmic reticulum stress through down regulation of Bip-ATF4-CHOP signaling pathway. Additionally, this natural polyphenol compound diminished cisplatin-induced DNA breaks and cellular apoptosis. The reduced type I collagen accumulation in the testis likely attributed from inhibition of TGFβ1, αSMA and ER protein TXNDC5 protein expression. The combinatorial beneficial effects better preserve spermatogenic layers and facilitate repopulation of sperm cells. Our study renders opportunity for re-introducing cisplatin to systemic anti-cancer therapy with reduced testicular toxicity and restored fertility.

scholarly journals DeepCDR: a hybrid graph convolutional network for predicting cancer drug response

2020 ◽  
Author(s):  
Qiao Liu ◽  
Zhiqiang Hu ◽  
Rui Jiang ◽  
Mu Zhou
Keyword(s):  
Drug Design ◽  
Cancer Biology ◽  
Drug Response ◽  
Drug Efficacy ◽  
Supplementary Information ◽  
Cancer Drug ◽  
Convolutional Network ◽  
Chemical Structures ◽  
Anti Cancer ◽  
Cancer Types

AbstractMotivationAccurate prediction of cancer drug response (CDR) is challenging due to the uncertainty of drug efficacy and heterogeneity of cancer patients. Strong evidences have implicated the high dependence of CDR on tumor genomic and transcriptomic profiles of individual patients. Precise identification of CDR is crucial in both guiding anti-cancer drug design and understanding cancer biology.ResultsIn this study, we present DeepCDR which integrates multi-omics profiles of cancer cells and explores intrinsic chemical structures of drugs for predicting cancer drug response. Specifically, DeepCDR is a hybrid graph convolutional network consisting of a uniform graph convolutional network (UGCN) and multiple subnetworks. Unlike prior studies modeling hand-crafted features of drugs, DeepCDR automatically learns the latent representation of topological structures among atoms and bonds of drugs. Extensive experiments showed that DeepCDR outperformed state-of-the-art methods in both classification and regression settings under various data settings. We also evaluated the contribution of different types of omics profiles for assessing drug response. Furthermore, we provided an exploratory strategy for identifying potential cancer-associated genes concerning specific cancer types. Our results highlighted the predictive power of DeepCDR and its potential translational value in guiding disease-specific drug design.AvailabilityDeepCDR is freely available at https://github.com/kimmo1019/[email protected]; [email protected] informationSupplementary data are available at Bioinformatics online.

scholarly journals 3D Collagen-Nanocellulose Matrices Model the Tumour Microenvironment of Pancreatic Cancer

2021 ◽  
Vol 3 ◽  
Author(s):  
Rodrigo Curvello ◽  
Verena Kast ◽  
Mohammed H. Abuwarwar ◽  
Anne L. Fletcher ◽  
Gil Garnier ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Three Dimensional ◽  
Tumour Microenvironment ◽  
Ductal Adenocarcinoma ◽  
Type I ◽  
3D Cultures ◽  
Tumour Spheroids ◽  
Cellulose Nanofibres ◽  
Anti Cancer ◽  
The Individual

Three-dimensional (3D) cancer models are invaluable tools designed to study tumour biology and new treatments. Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types of cancer, has been progressively explored with bioengineered 3D approaches by deconstructing elements of its tumour microenvironment. Here, we investigated the suitability of collagen-nanocellulose hydrogels to mimic the extracellular matrix of PDAC and to promote the formation of tumour spheroids and multicellular 3D cultures with stromal cells. Blending of type I collagen fibrils and cellulose nanofibres formed a matrix of controllable stiffness, which resembled the lower profile of pancreatic tumour tissues. Collagen-nanocellulose hydrogels supported the growth of tumour spheroids and multicellular 3D cultures, with increased metabolic activity and matrix stiffness. To validate our 3D cancer model, we tested the individual and combined effects of the anti-cancer compound triptolide and the chemotherapeutics gemcitabine and paclitaxel, resulting in differential cell responses. Our blended 3D matrices with tuneable mechanical properties consistently maintain the growth of PDAC cells and its cellular microenvironment and allow the screening of anti-cancer treatments.

scholarly journals Drug Repositioning of the α1-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug?

2020 ◽  
Vol 21 (15) ◽  
pp. 5339
Author(s):  
Romane Florent ◽  
Laurent Poulain ◽  
Monique N'Diaye
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Adrenergic Receptor ◽  
Drug Repositioning ◽  
Failure Process ◽  
Drug Repurposing ◽  
Cancer Drug ◽  
Cancer Management ◽  
Anti Cancer ◽  
Cancer Types

Failure of conventional treatments is often observed in cancer management and this requires the development of alternative therapeutic strategies. However, new drug development is known to be a high-failure process because of the possibility of a lower efficacy than expected for the drug or appearance of non-manageable side effects. Another way to find alternative therapeutic drugs consists in identifying new applications for drugs already approved for a particular disease: a concept named “drug repurposing”. In this context, several studies demonstrated the potential anti-tumour activity exerted by α1-adrenergic receptor antagonists and notably renewed interest for naftopidil as an anti-cancer drug. Naftopidil is used for benign prostatic hyperplasia management in Japan and a retrospective study brought out a reduced incidence of prostate cancer in patients that had been prescribed this drug. Further studies showed that naftopidil exerted anti-proliferative and cytotoxic effects on prostate cancer as well as several other cancer types in vitro, as well as ex vivo and in vivo. Moreover, naftopidil was demonstrated to modulate the expression of Bcl-2 family pro-apoptotic members which could be used to sensitise cancer cells to targeting therapies and to overcome resistance of cancer cells to apoptosis. For most of these anti-cancer effects, the molecular pathway is either not fully deciphered or shown to involve α1-adrenergic receptor-independent pathway, suggesting off target transduction signals. In order to improve its efficacy, naftopidil analogues were designed and shown to be effective in several studies. Thereby, naftopidil appears to display anti-cancer properties on different cancer types and could be considered as a candidate for drug repurposing although its anti-cancerous activities need to be studied more deeply in prospective randomized clinical trials.

Uptake of collagen type I via macropinocytosis cause mTOR activation and anti-cancer drug resistance

2020 ◽  
Vol 526 (1) ◽  
pp. 191-198 ◽  
Author(s):  
Shota Yamazaki ◽  
Yinghan Su ◽  
Ami Maruyama ◽  
Hideki Makinoshima ◽  
Jun Suzuki ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Collagen Type ◽  
Collagen Type I ◽  
Cancer Drug ◽  
Type I ◽  
Cancer Drug Resistance ◽  
Anti Cancer

scholarly journals Controlled pharmacokinetic anti-cancer drug concentration profiles lead to growth inhibition of colorectal cancer cells in a microfluidic device

Lab on a Chip ◽  
2020 ◽  
Vol 20 (17) ◽  
pp. 3167-3178
Author(s):  
Job Komen ◽  
Eiko Y. Westerbeek ◽  
Ruben W. Kolkman ◽  
Julia Roesthuis ◽  
Caroline Lievens ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Microfluidic Device ◽  
Concentration Profile ◽  
Cancer Drug ◽  
Concentration Profiles ◽  
Anti Cancer ◽  
Colorectal Cancer Cells ◽  
On Chip

We present a microfluidic device to expose cancer cells to a dynamic, in vivo-like concentration profile of a drug, and quantify efficacy on-chip.

scholarly journals Anti-Cancer Drug HMBA Acts as an Adjuvant during Intracellular Bacterial Infections by Inducing Type I IFN through STING

2017 ◽  
Vol 199 (7) ◽  
pp. 2491-2502 ◽  
Author(s):  
Akshamal Mihiranga Gamage ◽  
Kok-Onn Lee ◽  
Yunn-Hwen Gan
Keyword(s):  
Bacterial Infections ◽  
Cancer Drug ◽  
Type I ◽  
Type I Ifn ◽  
Anti Cancer

scholarly journals The Predictive Value of Low Skeletal Muscle Mass Assessed on Cross-Sectional Imaging for Anti-Cancer Drug Toxicity: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 9 (11) ◽  
pp. 3780
Author(s):  
Laura F. J. Huiskamp ◽  
Najiba Chargi ◽  
Lot A. Devriese ◽  
Anne M. May ◽  
Alwin D. R. Huitema ◽  
...  
Keyword(s):  
Systematic Review ◽  
Skeletal Muscle ◽  
Muscle Mass ◽  
Predictive Value ◽  
Drug Toxicity ◽  
Skeletal Muscle Mass ◽  
Meta Analysis ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Cancer Types

Low skeletal muscle mass (LSMM) is increasingly recognized for its predictive value for adverse events in cancer patients. In specific, the predictive value of LSMM has been demonstrated for anti-cancer drug toxicity in a variety of cancer types and anti-cancer drugs. However, due to the limited sample size and study populations focused on a single cancer type, an overall predictive value of LSMM for anti-cancer drug toxicity remains unknown. Therefore, this review aims to provide a comprehensive overview of the predictive value of LSMM and perform a meta-analysis to analyse the overall effect. A systematic search was conducted of MEDLINE, Scopus, EMBASE, and Cochrane. Inclusion criteria were skeletal muscle mass (SMM) evaluated with computed tomography (CT) or magnetic resonance imaging (MRI), articles published in English, SMM studied in humans, SMM measurement normalized for height, and patients did not receive an intervention to treat or prevent LSMM. A meta-analysis was performed using a random-effects model and expressed in odds ratio (OR) with 95% confidence interval (CI). Heterogeneity was assessed using χ2 and I2 statistics. The search yielded 907 studies. 31 studies were included in the systematic review. Sample sizes ranged from 21 to 414 patients. The occurrence of LSMM ranged from 12.2% to 89.0%. The most frequently studied cancer types were oesophageal, renal, colorectal, breast, and head and neck cancer. Patients with LSMM had a higher risk of severe toxicity (OR 4.08; 95% CI 2.48–6.70; p < 0.001) and dose-limiting toxicity (OR 2.24; 95% CI 1.28–3.92; p < 0.001) compared to patients without LSMM. To conclude, the predictive value of LSMM for anti-cancer drug toxicity can be observed across cancer types. This information increases the need for further research into interventions that could treat LSMM as well as the possibility to adapt treatment regimens based on the presence of LSMM.

scholarly journals Fabrication of low-cost micropatterned polydimethyl-siloxane scaffolds to organise cells in a variety of two-dimensioanl biomimetic arrangements for lab-on-chip culture platforms

2017 ◽  
Vol 8 ◽  
pp. 204173141774150 ◽  
Author(s):  
Lidia Escutia-Guadarrama ◽  
Genaro Vázquez-Victorio ◽  
David Martínez-Pastor ◽  
Brenda Nieto-Rivera ◽  
Marcela Sosa-Garrocho ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Type I Collagen ◽  
Microcontact Printing ◽  
Low Cost ◽  
Extracellular Matrix Protein ◽  
Type I ◽  
Human Hepatoma Cells ◽  
Lab On Chip ◽  
Chip Technology ◽  
On Chip

We present the rapid-prototyping of type I collagen micropatterns on poly-dimethylsiloxane substrates for the biomimetic confinement of cells using the combination of a surface oxidation treatment and 3-aminopropyl triethoxysilane silanisation followed by glutaraldehyde crosslinking. The aim of surface treatment is to stabilise microcontact printing transfer of this natural extracellular matrix protein that usually wears out easily from poly-dimethylsiloxane, which is not suitable for biomimetic cell culture platforms and lab-on-chip applications. A low-cost CD-DVD laser was used to etch biomimetic micropatterns into acrylic sheets that were in turn replicated to poly-dimethylsiloxane slabs with the desired features. These stamps were finally inked with type I collagen for microcontact printing transfer on the culture substrates in a simple manner. Human hepatoma cells (HepG2) and rat primary hepatocytes, which do not adhere to bare poly-dimethylsiloxane, were successfully seeded and showed optimal adhesion and survival on simple protein micropatterns with a hepatic cord geometry in order to validate our technique. HepG2 cells also proliferated on the stamps. Soft and stiff poly-dimethylsiloxane layers were also tested to demonstrate that our cost-effective process is compatible with biomimetic organ-on-chip technology integrating tunable stiffness with a potential application to drug testing probes development where such cells are commonly used.

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