scholarly journals Comprehensive transcriptomic analysis of cell lines as models of primary tumor samples across 22 tumor types

2018 ◽  
Author(s):  
K. Yu ◽  
B. Chen ◽  
D. Aran ◽  
J. Charalel ◽  
A. Butte ◽  
...  
Keyword(s):  
Cancer Research ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Primary Tumor ◽  
Cancer Biology ◽  
Cancer Cell Lines ◽  
Primary Tumors ◽  
Tumor Types

AbstractCancer cell lines are commonly used as models for cancer biology. While they are limited in their ability to capture complex interactions between tumors and their surrounding environment, they are a cornerstone of cancer research and many important findings have been discovered utilizing cell line models. Not all cell lines are appropriate models of primary tumors, however, which may contribute to the difficulty in translating in vitro findings to patients. Previous studies have leveraged public datasets to evaluate cell lines as models of primary tumors, but they have been limited in scope to specific tumor types and typically ignore the presence of tumor infiltrating cells in the primary tumor samples. We present here a comprehensive pan-cancer analysis utilizing approximately 9,000 transcriptomic profiles from The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia to evaluate cell lines as models of primary tumors across 22 different tumor types. After adjusting for tumor purity in the primary tumor samples, we performed correlation analysis and differential gene expression analysis between the primary tumor samples and cell lines. We found that cell-cycle pathways are consistently upregulated in cell lines, while no pathways are consistently upregulated across the primary tumor samples. In a case study, we compared colorectal cancer cell lines with primary tumor samples across the colorectal subtypes and identified three colorectal cell lines that were derived from fibroblasts rather than tumor epithelial cells. Lastly, we propose a new set of cell lines panel, the TCGA-110, which contains the most representative cell lines from 22 different tumor types as a more comprehensive and informative alternative to the NCI-60 panel. Our analysis of the other tumor types are available in our web app (http://comphealth.ucsf.edu/TCGA110) as a resource to the cancer research community, and we hope it will allow researchers to select more appropriate cell line models and increase the translatability of in vitro findings.

ANTITUMOR EFFECT OF SUNITINIB AND BORTEZOMIB ON BREAST CANCER CELL LINE IN VITRO

2017 ◽  
Vol 63 (1) ◽  
pp. 141-145
Author(s):  
Yuliya Khochenkova ◽  
Eliso Solomko ◽  
Oksana Ryabaya ◽  
Yevgeniya Stepanova ◽  
Dmitriy Khochenkov
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Antitumor Effect ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Actual Problem

The discovery for effective combinations of anticancer drugs for treatment for breast cancer is the actual problem in the experimental chemotherapy. In this paper we conducted a study of antitumor effect of the combination of sunitinib and bortezomib against MDA-MB-231 and SKBR-3 breast cancer cell lines in vitro. We found that bortezomib in non-toxic concentrations can potentiate the antitumor activity of sunitinib. MDA-MB-231 cell line has showed great sensitivity to the combination of bortezomib and sunitinib in vitro. Bortezomib and sunitinib caused reduced expression of receptor tyrosine kinases VEGFR1, VEGFR2, PDGFRa, PDGFRß and c-Kit on HER2- and HER2+ breast cancer cell lines

Design, Synthesis, Molecular Docking, and Anticancer Evaluation of Pyrazole Linked Pyrazoline Derivatives with Carbothioamide Tail as EGFR Kinase Inhibitors

2020 ◽  
Vol 21 (1) ◽  
pp. 42-60
Author(s):  
Farah Nawaz ◽  
Ozair Alam ◽  
Ahmad Perwez ◽  
Moshahid A. Rizvi ◽  
Mohd. Javed Naim ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Kinase Assay ◽  
Cervix Uteri ◽  
Egfr Kinase

Background: The Epidermal Growth Factor Receptor (known as EGFR) induces cell differentiation and proliferation upon activation through the binding of its ligands. Since EGFR is thought to be involved in the development of cancer, the identification of new target inhibitors is the most viable approach, which recently gained momentum as a potential anticancer therapy. Objective: To assess various pyrazole linked pyrazoline derivatives with carbothioamide for EGFR kinase inhibitory as well as anti-proliferative activity against human cancer cell lines viz. A549 (non-small cell lung tumor), MCF-7 (breast cancer cell line), SiHa (cancerous tissues of the cervix uteri), and HCT-116 (colon cancer cell line). Methods: In vitro EGFR kinase assay, in vitro MTT assay, Lactate dehydrogenase release, nuclear staining (DAPI), and flow cytometry cell analysis. Results: Compounds 6h and 6j inhibited EGFR kinase at concentrations of 1.66μM and 1.9μM, respectively. Furthermore, compounds 6h and 6j showed the most potent anti-proliferative results against the A549 KRAS mutation cell line (IC50 = 9.3 & 10.2μM). Through DAPI staining and phase contrast microscopy, it was established that compounds 6h and 6j also induced apoptotic activity in A549 cells. This activity was further confirmed by FACS using Annexin-V-FITC and Propidium Iodide (PI) labeling. Molecular docking studies performed on 6h and 6j suggested that the compounds can bind to the hinge region of ATP binding site of EGFR tyrosine kinase in a similar pose as that of the standard drug gefitinib. Conclusion: The potential anticancer activity of compounds 6h and 6j was confirmed and need further exploration in cancer cell lines of different tissue origin and signaling pathways, as well as in animal models of cancer development.

scholarly journals Implementation of the NCI-60 Human Tumor Cell Line Panel to Screen 2260 Cancer Drug Combinations to Generate >3 Million Data Points Used to Populate a Large Matrix of Anti-Neoplastic Agent Combinations (ALMANAC) Database

2018 ◽  
Vol 24 (3) ◽  
pp. 242-263 ◽  
Author(s):  
David A. Close ◽  
Allen Xinwei Wang ◽  
Stanton J. Kochanek ◽  
Tongying Shun ◽  
Julie L. Eiseman ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Growth Inhibition ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cancer Drug ◽  
Large Matrix ◽  
Data Points

Animal and clinical studies demonstrate that cancer drug combinations (DCs) are more effective than single agents. However, it is difficult to predict which DCs will be more efficacious than individual drugs. Systematic DC high-throughput screening (HTS) of 100 approved drugs in the National Cancer Institute’s panel of 60 cancer cell lines (NCI-60) produced data to help select DCs for further consideration. We miniaturized growth inhibition assays into 384-well format, increased the fetal bovine serum amount to 10%, lengthened compound exposure to 72 h, and used a homogeneous detection reagent. We determined the growth inhibition 50% values of individual drugs across 60 cell lines, selected drug concentrations for 4 × 4 DC matrices (DCMs), created DCM master and replica daughter plate sets, implemented the HTS, quality control reviewed the data, and analyzed the results. A total of 2620 DCMs were screened in 60 cancer cell lines to generate 3.04 million data points for the NCI ALMANAC (A Large Matrix of Anti-Neoplastic Agent Combinations) database. We confirmed in vitro a synergistic drug interaction flagged in the DC HTS between the vinca-alkaloid microtubule assembly inhibitor vinorelbine (Navelbine) tartrate and the epidermal growth factor-receptor tyrosine kinase inhibitor gefitinib (Iressa) in the SK-MEL-5 melanoma cell line. Seventy-five percent of the DCs examined in the screen are not currently in the clinical trials database. Selected synergistic drug interactions flagged in the DC HTS described herein were subsequently confirmed by the NCI in vitro, evaluated mechanistically, and were shown to have greater than single-agent efficacy in mouse xenograft human cancer models. Enrollment is open for two clinical trials for DCs that were identified in the DC HTS. The NCI ALMANAC database therefore constitutes a valuable resource for selecting promising DCs for confirmation, mechanistic studies, and clinical translation.

CHEMOTHERAPEUTIC POTENTIAL OF NOVEL XANTHONE SOURCED FROM SWERTIA CHIRATA AGAINST SKIN CARCINOGENESIS

2020 ◽  
pp. 84-88
Author(s):  
ATISH BARUA ◽  
PRITHA CHOUDHURY ◽  
CHINMAY KUMAR PANDA ◽  
PROSENJIT SAHA
Keyword(s):  
Skin Cancer ◽  
Antitumor Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Self Renewal ◽  
Qrt Pcr ◽  
Swertia Chirata

Objective: Swertia chirata forms a rich source of bio-active compounds, among which xanthones form an important part. Among the xanthones present in it, 1,5,8 Tri-hydroxy-3-methoxy xanthone (TMX) was found to be the most active. The present study aims to evaluate the chemotherapeutic potential of it against metastatic skin cancer cell lines. Methods: In this study, the antitumor activity of TMX (the active component of chirata plant) was evaluated in A431, SKMEL-5, and A375 cell line by using in-vitro assays such as cell viability assay, cell cycle analysis, caspase 3 activity assay, intracellular reactive oxygen species (ROS) level determination by dichlorofluorescein diacetate, and quantitative real-time polymerase chain reaction (qRT-PCR). Results: In vitro studies showed that TMX from S. chirata exhibited significant antitumor activity by inducing apoptosis and restricting proliferation in both melanoma and non-melanoma skin cancer cell lines, but no such activity was seen in normal skin cancer cell line WS1. The qRT-PCR analysis revealed that in both the melanoma ad non-melanoma cell lines, TMX could exert its antitumor activity by downregulating c-Myc, cyclin-D1, and β-catenin and up-regulating Wnt antagonist gsk-3β, thereby suppressing wnt self-renewal pathway, but such regulation was absent in normal cell line. Conclusions: TMX from chirata could effectively inhibit the proliferation of metastatic skin cancer (both melanoma and non-melanoma) cell lines while being non-toxic to normal cell lines. The chemotherapeutic potential of TMX against metastatic skin cancer cell lines was achieved by downregulating several key regulatory genes enabling the suppression of the self-renewal pathway, the chief reason behind the invasiveness of cancer cells.

scholarly journals Synthesis and Antitumour activity of some aryl semicarbazones

2000 ◽  
Vol 68 (4) ◽  
pp. 369-377 ◽  
Author(s):  
S.N. Pandeya ◽  
P. Yogeeswari ◽  
E.A. Sausville ◽  
A.B. Mauger ◽  
V.L. Narayanan
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Tumour Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Significant Activity

Various 4-substituted phenyl semicarbazone derivatives were synthesized and evaluated in vitro by NCI in the 3-cell line, one dose primary anticancer assay. Three compounds showed significant activity against breast MCF7 cell line and were further evaluated for potential anticancer activity in an in vitro human disease-oriented tumour cell line screening panel that consisted of 60 human tumour cell lines arranged in nine subpanels, representing diverse histologies. Leukemia, colon, ovarian and breast cancer cell lines were relatively more sensitive to these compounds than the other cell lines. The 4-carboxy substituted p-nitrobenzylidene phenyl semicarbazone (1c) emerged as the most active compound with average GI50 value (the molar drug concentration required for the 50% growth inhibition) of 28.6µM. This compound showed greater activity than methotrexate against NCI-H226(Lung), BT-549 and T-47D(Breast) cancer cell lines.

Brave New Hope for Breast Cancer Aminopyrazole derivates between rational design and clinical efficacy

2017 ◽  
Vol 68 (4) ◽  
pp. 754-757 ◽  
Author(s):  
George Mihai Nitulescu ◽  
George Iancu ◽  
Georgiana Nitulescu ◽  
Raluca Claudia Iancu ◽  
Camelia Bogdanici ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Biology ◽  
Rational Design ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Proliferative Effect

Breast cancer research is a priority nowadays because of the high burden the disease represents for health systems worldwide. New agents are intensively researched to overcome breast cancer biology. Our aminopyrazole derivatives showed promising results when tested in vitro on breast cancer cell lines, by inhibiting protein kinase pathways. Anti-proliferative effect of pyrazole compounds on different breast cancer cell lines was heterogeneous. Further research is necessary to design the optimal structure in terms of high antitumor efficacy and good safety profile. Ophthalmologist control is very important for patients with breast cancer because treatment with some drugs reported side ocular effects: cataract, maculopathy (crystals or drusen or yellowish spots), retinal hemorrhages or dry.

scholarly journals Exploring the classification of cancer cell lines from multiple omic views

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9440
Author(s):  
Xiaoxi Yang ◽  
Yuqi Wen ◽  
Xinyu Song ◽  
Song He ◽  
Xiaochen Bo
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Cancer Classification ◽  
Omics Data ◽  
Primary Tumors ◽  
Pan Cancer

Background Cancer classification is of great importance to understanding its pathogenesis, making diagnosis and developing treatment. The accumulation of extensive omics data of abundant cancer cell line provide basis for large scale classification of cancer with low cost. However, the reliability of cell lines as in vitro models of cancer has been controversial. Methods In this study, we explore the classification on pan-cancer cell line with single and integrated multiple omics data from the Cancer Cell Line Encyclopedia (CCLE) database. The representative omics data of cancer, mRNA data, miRNA data, copy number variation data, DNA methylation data and reverse-phase protein array data were taken into the analysis. TumorMap web tool was used to illustrate the landscape of molecular classification.The molecular classification of patient samples was compared with cancer cell lines. Results Eighteen molecular clusters were identified using integrated multiple omics clustering. Three pan-cancer clusters were found in integrated multiple omics clustering. By comparing with single omics clustering, we found that integrated clustering could capture both shared and complementary information from each omics data. Omics contribution analysis for clustering indicated that, although all the five omics data were of value, mRNA and proteomics data were particular important. While the classifications were generally consistent, samples from cancer patients were more diverse than cancer cell lines. Conclusions The clustering analysis based on integrated omics data provides a novel multi-dimensional map of cancer cell lines that can reflect the extent to pan-cancer cell lines represent primary tumors, and an approach to evaluate the importance of omic features in cancer classification.

scholarly journals Transcriptional fidelity enhances cancer cell line selection in pediatric cancers

2021 ◽  
Author(s):  
Cuyler Luck ◽  
Katharine Yu ◽  
Ross A Okimoto ◽  
Marina Sirota
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Molecular Subtype ◽  
Unmet Need ◽  
Cancer Cell Lines ◽  
Tumor Type ◽  
Pediatric Cancers ◽  
Public Data ◽  
Tumor Types

Multi-omic technologies have allowed for comprehensive profiling of patient-derived tumor samples and the cell lines that are intended to model them. Yet, our understanding of how cancer cell lines reflect native pediatric cancers in the age of molecular subclassification remains unclear and represents a clinical unmet need. Here we use Treehouse public data to provide an RNA-seq driven analysis of 799 cancer cell lines, focusing on how well they correlate to 1,655 pediatric tumor samples spanning 12 tumor types. For each tumor type we present a ranked list of the most representative cell lines based on correlation of their transcriptomic profiles to those of the tumor. We found that most (8/12) tumor types best correlated to a cell line of the closest matched disease type. We furthermore showed that inferred molecular subtype differences in medulloblastoma significantly impacted correlation between medulloblastoma tumor samples and cell lines. Our results are available as an interactive web application to help researchers select cancer cell lines that more faithfully recapitulate pediatric cancer.

scholarly journals Evaluation of In Vitro Anti-Cancer Activity of Kukkutanakhi Guggula on Liver, Prostrate, Ovary and Renal Cancer

2020 ◽  
Vol 11 (3) ◽  
pp. 491-496
Author(s):  
Mujahid B Khan ◽  
Ninad Sathe ◽  
Bharat Rathi
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Renal Cancer ◽  
Hepatoma Cell ◽  
Cancer Cell Lines ◽  
Hepatoma Cell Line ◽  
Moderate Activity ◽  
Commiphora Mukul

The medicines prepared by using exudates of Commiphora mukul (Stocks) Hook. are described in Ayurveda under Guggula Kalpana which are among such valuable dosage forms. According to retrospective literary review, the combination of Kukkutnaki (Aspidium cicutarium Sw.) and purified Guggula(Commiphora mukul (Stocks) Hook.) was first mentioned in the book Chikitsa pradeep named as Kukkutnaki Guggula. Since last 3 decades, it was documented as an herbal drug which is used for cysts, goiter, tumors, tonsillitis, abscess, mansvaha strotas ailments, which are burning issues worldwide. Due to its observed clinical efficacy in Arbuda (~Cancer), the current in-vitro anticancer study was conducted with an aim to check its anticancer effect on human hepatoma cell line-HEPG2 of Liver; PC-3 and DU145 cancer cell lines of Prostate; Ovcar-3, A2780, SK-OV-3, PA-1 cancer cell lines of Ovary and ACHN renal cancer cell line of Kidney. The current in vitro study was conducted at ACTREC, Kharghar, Navi Mumbai. The selected cancer cell lines were procured from ATCC, USA and NCCS Pune. The Sulforhodamine B (SRB) Assay protocol was followed to observe the activity of the study drug. The positive control was Adriamycin in the study. The growth curve graphs were plotted and LC50, GI50, TGI values were calculated. Kukkutnakhi Guggula was found safe for oral administration, non- toxic at cellular level (LC50 values were > 160) and have moderate activity on HEPG2, Ovcar-3, DU145, ACHN cancer cell lines and had shown negligible activity on A2780, SK-OV-3, PA-1 and PC-3 cell lines. This work provides scope to study its effect on targeted cancers, specific in vivo scientific studies and human clinical trials for further researchers.

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