scholarly journals Expression Atlas of FGF and FGFR Genes in Pancancer Uncovered Predictive Biomarkers for Clinical Trials of Selective FGFR Inhibitors

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuan Li ◽  
Long Wu ◽  
Weiping Tao ◽  
Dawei Wu ◽  
Fei Ma ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Tumor Cell ◽  
Cell Lines ◽  
Expression Profiles ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Tumor Cell Lines ◽  
Expression Atlas ◽  
Tumor Types

Background. Clinical trials based on FGFR mutation or amplification as a druggable target of FGFR inhibitors have produced disappointing clinical outcomes. Therefore, the identification of predictive biomarkers for FGFR-targeted agents has remained a crucial issue. Methods. Expression profiles of FGFs and FGFRs in 8,111 patients with 24 types of solid tumors and 879 tumor cell lines along with drug sensitivity data were obtained and followed by integrative bioinformatics analysis. Results. FGFs and FGFRs were frequently dysregulated in pancancer. Most of the expression of FGFs and FGFRs were significantly associated with overall survival in at least two cancer types. Moreover, tumor cell lines with high FGFR1/3 expression were more sensitive to FGFR inhibitor PD173074, especially in breast, liver, lung and ovarian cancer. The predicted positive ratios of FGFR1-4 were generally over 10% in most tumor types, especially in squamous cell carcinoma. High positive FGFR1 or 3 expression ratios were predicted in cholangiocarcinoma (58%), followed by bladder cancer (42%), endometrial carcinoma (35%), and ovarian cancer (34%). Conclusions. FGFR expression was a promising predictive biomarker for FGFR inhibition response in clinical trials, and different combinations of FGFR genes should be used in screening for patients in certain tumor types.

Generation of a HuTCR mouse platform-derived MAGE-A1-directed high-affinity TCR with superior potency versus human-derived TCRs.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14515-e14515
Author(s):  
Ioannis Gavvovidis ◽  
Matthias Leisegang ◽  
Jenifer Oduro ◽  
Matthias Obenaus ◽  
Eugen Leo ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Cell ◽  
Cell Lines ◽  
Target Cells ◽  
Tumor Cell Lines ◽  
Functional Avidity ◽  
High Affinity ◽  
Selective Expression ◽  
Tumor Types ◽  
Cancer Testis

e14515 Background: As cancer-testis antigens are self-antigens, T cells expressing high-affinity TCRs against such antigens are suppressed via negative thymic selection. Therefore, patient- or donor-derived TCRs are typically of low affinity and result in a reduced antitumor effect. Using our proprietary HuTCR platform, which consists of mouse lines carrying the full human TCR α/β loci in combination with common human HLA alleles, we have isolated high-affinity TCRs specific for the cancer-testis antigen MAGE-A1 and compared them to human-derived MAGE-A1-specific TCRs that are currently reported to be in clinical development. Furthermore, we validated MAGE-A1 as a potential cancer therapy target by using immunohistochemistry to evaluate expression in several major tumor types and healthy tissue. Methods: Using scRNAseq, TCRs were isolated from HuTCR mice. Human-derived MAGE-A1-specific TCR sequences were obtained from publicly available databases. All TCRs were expressed in primary human T cells as verified using peptide-MHC-multimer staining. Functional avidity of the TCRs was analyzed by coculture with T2 target cells loaded with titrated amounts of epitope peptides and measuring cytokine concentration by ELISA. Reactivity of TCRs to endogenously processed MAGE-A1 protein was assessed by co-culture with a panel of tumor cell lines varying in MAGE-A1 and/or MHC-class-I expression. MAGE-A1 expression on protein level was evaluated by immunohistochemistry. Results: Immunization of HuTCR mice with the antigen resulted in robust CD8+ T cell responses and several TCR clonotypes were identified by scRNAseq, with the majority of clonotypes being specific to the MAGE-A1-derived peptide KVLEYVIKV and TCR affinities ranging from 0.3 nM to 3 nM. By comparison, human-derived TCRs exhibited generally lower functional avidity from 3 nM to 60 nM. In addition, HuTCR-mouse-derived TCRs were more sensitive in recognition of tumor cell lines expressing low MAGE-A1 and/or HLA-A2. Immunohistochemical analysis of MAGE-A1 expression in healthy tissues demonstrated highly selective expression of MAGE-A1 in testis, only. Screening for expression confirmed that a significant proportion of several major cancer types expresses MAGE-A1 as reported by various other groups [reviewed in Curr Opin Cell Biol. 2015 December; 37: 1–8]. Conclusions: The HuTCR mouse platform allows for the generation of high-affinity MAGE-A1-specific TCRs with increased anti-tumor efficacy as compared to human-derived TCRs against the same cancer antigen. In addition, it was confirmed that MAGE-A1 has a highly selective expression pattern in healthy tissues (testis, only), but shows distinct expression in several major human tumor types.

scholarly journals Human Thyroid Tumor Cell Lines Derived from Different Tumor Types Present a Common Dedifferentiated Phenotype

2007 ◽  
Vol 67 (17) ◽  
pp. 8113-8120 ◽  
Author(s):  
Wilma C.G. van Staveren ◽  
David Weiss Solís ◽  
Laurent Delys ◽  
Laurence Duprez ◽  
Guy Andry ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Thyroid Tumor ◽  
Human Thyroid ◽  
Tumor Cell Lines ◽  
Tumor Types

scholarly journals A Panel of Four Anti-HSPG Monoclonal Antibodies Benefits in Increasing the Specificity in Detection of Colorectal Cancer

2021 ◽  
Vol 20 (3) ◽  
Author(s):  
Ei Khaing Mon ◽  
Rujurek Chaiwongsa ◽  
Phennapha Klangsinsirikul ◽  
Preeyanat Vongchan
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
Cell Lines ◽  
Cancer Cell ◽  
Blood Cells ◽  
White Blood Cells ◽  
Predictive Biomarkers ◽  
Future Research ◽  
Tumor Cell Lines

Colorectal cancer (CRC) is the second leading with main cause of death is liver and lung metastasis. Using of a combination of genetic and epigenetic markers are addressed but the results have not been approved in clinical practice. A set of serum biomarkers has been proposed to increase accuracy in early diagnosis of CRC. In addition, non-invasive as well as the best prognostic panel of biomarkers and define predictive biomarkers for treatment of CRC are all aims of future research. HSPGs is an important biomolecule involving in cancer cell proliferation, differentiation, and migration. Membrane HSPGs shed into blood circulation and matrix in particular circumstance can be used as a specific biomarker for some cancer cells. In order to evaluate the benefit of a panel of anti-HSPGs monoclonal antibodies in increasing specificity to detect CRC, four clones of anti-HSPGs were studied for its specific reaction on various tumor cell lines by indirect immunofluorescent technique and analyzed by flow cytometer compared to normal white blood cells. A combination of two or more clones were focused. The results showed that all four clones presented a variation in reaction to all solid tumor cell lines tested but negative to normal white blood cells from different ABO blood groups. Interestingly, amongst those cells tested, HT29, a colorectal cancer cell lines were significantly reacted with all four monoclonal antibodies. Taken together, we proposed a panel of four anti-HSPGs monoclonal antibodies to be applied in various detection platforms to increase the specificity in screening of CRC. Keywords: Cancer biomarkers, Colorectal cancer, HSPG

Absence of functional EpoR expression in human tumor cell lines

Blood ◽  
2010 ◽  
Vol 115 (21) ◽  
pp. 4254-4263 ◽  
Author(s):  
Susan Swift ◽  
Aaron R. Ellison ◽  
Paul Kassner ◽  
Ian McCaffery ◽  
John Rossi ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Human Tumor ◽  
Mrna Levels ◽  
Tumor Cell Lines ◽  
Human Tumor Cell Lines ◽  
Protein Levels ◽  
And Function ◽  
Tumor Types ◽  
Positive Controls

Certain oncology trials showed worse clinical outcomes in the erythropoiesis-stimulating agent (ESA) arm. A potential explanation was that ESA-activated erythropoietin (Epo) receptors (EpoRs) promoted tumor cell growth. Although there were supportive data from preclinical studies, those findings often used invalidated reagents and methodologies and were in conflict with other studies. Here, we further investigate the expression and function of EpoR in tumor cell lines. EpoR mRNA levels in 209 human cell lines representing 16 tumor types were low compared with ESA-responsive positive controls. EpoR protein production was evaluated in a subset of 66 cell lines using a novel anti-EpoR antibody. EpoR+ control cells had an estimated 10 000 to 100 000 EpoR dimers/cell. In contrast, 54 of 61 lines had EpoR protein levels lower than 100 dimers/cell. Cell lines with the highest EpoR protein levels (400-3200 dimers/cell) were studied further, and, although one line, NCI-H661, bound detectable levels of [125I]–recombinant human Epo (rHuEpo), none showed evidence of ESA-induced EpoR activation. There was no increased phosphorylation of STAT5, AKT, ERK, or S6RP with rHuEpo. In addition, EpoR knockdown with siRNAs did not affect viability in 2 cell lines previously reported to express functional EpoR (A2780 and SK-OV-3). These results conflict with the hypothesis that EpoR is functionally expressed in tumors.

Interaction of Human Tumor Cells with Human Platelets and the Coagulation System

1983 ◽  
Vol 50 (03) ◽  
pp. 726-730 ◽  
Author(s):  
Hamid Al-Mondhiry ◽  
Virginia McGarvey ◽  
Kim Leitzel
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Human Tumor ◽  
Human Platelets ◽  
Factor Vii ◽  
Coagulation System ◽  
Breast Adenocarcinoma ◽  
Activate Factor ◽  
Tumor Cell Lines

SummaryThis paper reports studies on the interaction between human platelets, the plasma coagulation system, and two human tumor cell lines grown in tissue culture: Melanoma and breast adenocarcinoma. The interaction was monitored through the use of 125I- labelled fibrinogen, which measures both thrombin activity generated by cell-plasma interaction and fibrin/fibrinogen binding to platelets and tumor cells. Each tumor cell line activates both the platelets and the coagulation system simultaneously resulting in the generation of thrombin or thrombin-like activity. The melanoma cells activate the coagulation system through “the extrinsic pathway” with a tissue factor-like effect on factor VII, but the breast tumor seems to activate factor X directly. Both tumor cell lines activate platelets to “make available” a platelet- derived procoagulant material necessary for the conversion of prothrombin to thrombin. The tumor-derived procoagulant activity and the platelet aggregating potential of cells do not seem to be inter-related, and they are not specific to malignant cells.

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