scholarly journals Screening Antitumor Bioactive Fraction from Sauromatum giganteum (Engl.) Cusimano & Hett and Sensitive Cell Lines with the Serum Pharmacology Method and Identification by UPLC-TOF-MS

Molecules ◽  
2015 ◽  
Vol 20 (3) ◽  
pp. 4290-4306 ◽  
Author(s):  
Shi-Yong Gao ◽  
Yun-Fei Gong ◽  
Qiu-Jia Sun ◽  
Jing Bai ◽  
Long Wang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Sensitive Cell ◽  
Bioactive Fraction ◽  
Serum Pharmacology ◽  
Tof Ms

scholarly journals Gene expression studies in radiation-sensitive cell lines

2005 ◽  
Vol 7 (S2) ◽  
Author(s):  
J Aarøe ◽  
R Gatti ◽  
A-L Børresen-Dale ◽  
O Rødningen
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Sensitive Cell ◽  
Expression Studies ◽  
Gene Expression Studies

scholarly journals Correction: Integrated single-cell and bulk gene expression and ATAC-seq reveals heterogeneity and early changes in pathways associated with resistance to cetuximab in HNSCC-sensitive cell lines

2020 ◽  
Vol 123 (10) ◽  
pp. 1582-1583 ◽  
Author(s):  
Luciane T. Kagohara ◽  
Fernando Zamuner ◽  
Emily F. Davis-Marcisak ◽  
Gaurav Sharma ◽  
Michael Considine ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Cell Lines ◽  
Sensitive Cell

scholarly journals Interferon increases HLA synthesis in melanoma cells: interferon-resistant and -sensitive cell lines.

1982 ◽  
Vol 79 (10) ◽  
pp. 3265-3269 ◽  
Author(s):  
T. Y. Basham ◽  
M. F. Bourgeade ◽  
A. A. Creasey ◽  
T. C. Merigan
Keyword(s):  
Cell Lines ◽  
Melanoma Cells ◽  
Sensitive Cell

scholarly journals Monoclonal antibodies reactive with the mouse interleukin 5 receptor.

1989 ◽  
Vol 169 (5) ◽  
pp. 1693-1701 ◽  
Author(s):  
A G Rolink ◽  
F Melchers ◽  
R Palacios
Keyword(s):  
B Lymphocytes ◽  
Cell Lines ◽  
Binding Sites ◽  
Lymphoid Cells ◽  
Sensitive Cell ◽  
Spleen Cells ◽  
Interleukin 5 ◽  
Cell Responses ◽  
Adult Mice ◽  
Proliferative Cell

The rat mAbs R52.120 and R52.625 inhibit the action of IL-5 on both IL-5-sensitive cell lines and freshly isolated splenic B lymphocytes. Neither antibody inhibits the proliferative cell responses promoted by IL-2, IL-3, or IL-4. Purified R52.120+ lymphoid spleen cells contain 15-20-fold higher numbers of B lymphocytes responding to IL-5 in the form of maturation into antibody-producing cells. By immunofluorescence staining and flow fluorocytometry, the R52.120 and R52.625 antibodies bound to all 12 IL-5-sensitive cell lines tested. Both antibodies react with 2-4% cells in the spleen, 5% lymphoid cells, and 10-15% myeloid cells in the bone marrow, and 10-14% in the peritoneum of C57BL/6, DBA/2, and BALB/c adult mice. No positive cells for either antibody were detected in the thymus and lymph nodes of these mice. Both R52.120 and R52.625 antibodies specifically inhibit the binding of radiolabeled IL-5 to its receptor. Finally, R52.120 and R52.625 antibodies precipitate from 35S-methionine-labeled IL-5-R+ cell lysates three proteins with Mr 46,000, 130,000, and 140,000. Taken together from these results, we conclude that the R52.120 and R52.625 mAbs recognize epitopes on the IL-5-R complex very close or identical to the IL-5 binding sites.

Identification of a Diagnostic Gene Signature for SGN-40, Anti-CD40 Monoclonal Antibody, in Pre-Clinical NHL Models and the Role of FAS in SGN-40 Mediated Apoptosis.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1593-1593
Author(s):  
Xiaoyan Shi ◽  
Bart Burington ◽  
Tom Januario ◽  
Jeffrey T Lau ◽  
Shang-Fan Yu ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
B Cell ◽  
Cell Lines ◽  
Germinal Center ◽  
Gene Signature ◽  
Resistant Cell ◽  
Lymphoma Cell ◽  
Hodgkin's Lymphoma ◽  
Sensitive Cell ◽  
Non Hodgkin's Lymphoma

Abstract SGN-40, an anti-CD40 monoclonal antibody, is a humanized IgG1 antibody that binds to CD40, mediates effector cell functions (ADCC/ADCP) and activates downstream signaling pathways. SGN-40 has shown activity in a phase I single agent multi-dose trial in non Hodgkin’s lymphoma, with greatest activity in diffuse large B-cell lymphoma (Advani et al. 2008, ICML). Previous in vitro studies implicated down-regulation of the germinal center expressed protein Bcl-6, upregulation of p53 family member TAp63a, and FAS death receptor induction as potential mechanisms leading to lymphoma cell death (Lewis et al. 2007, AACR, ASH). In order to further define the apoptosis signaling mechanism, we assessed the ability of SGN-40 to inhibit proliferation and promote apoptosis across a large panel of non-Hodgkin’s lymphoma cell lines. SGN-40 reduced cell viability in 58% (18/31) of cell lines tested. To identify the genes that may be promoting apoptosis and/or inhibiting proliferation, we compared gene expression levels before and after SGN-40 exposure in both sensitive and resistant cell lines, as well as in normal B-cells. SGN-40 strikingly and specifically upregulated FAS on the cell surface of sensitive cell lines. Furthermore, the addition of soluble FAS-Fc dampened SGN-40-induced apoptosis in a subset of sensitive cell lines, suggesting a dependence on a FAS-FASL interaction. These data imply that FAS-dependent apoptosis may directly contribute to the anti-tumor effect of SGN-40. Our data also demonstrate that SGN-40 sensitivity is dependent on the point in B-cell development at which the NHL cell lines were transformed. Sensitive cell lines had a gene signature characteristic of minimal activation of CD40 signaling prior to SGN-40 exposure, whereas resistant cell lines had a signature consistent with prior constitutive signaling downstream of CD40. Thus, SGN-40 appears to elicit its apoptotic properties through activation of CD40 signaling in NHL cell lines not previously exposed to CD40L signaling in the germinal center environment at the time of lymphocyte transformation (GCB lymphomas). In order to develop a clinically feasible assay from FFPE tissue, we developed a 14-gene signature by Stepwise Linear Modeling, utilizing genes from the CD40 pathway activation and GCB gene sets; the classifier gave >96% accuracy (30/31) on the ‘training’ set of cell lines and 75% (3/4) accuracy on a ‘test’ set of xenografts. Overall, our data provides unique insights into SGN-40 mechanisms of action, provides a testable hypothesis of the clinical mechanism of action, and a potential diagnostic test to identify patients more likely to benefit from SGN-40. Efforts are currently underway to test the clinical relevance of these findings.

Difference of Drug-Resistance between Single-Factor Resistance Cell Line K562/MDR1 Transfected with mdr1 Gene and Multi-Factor Resistance Cell Line K562/A02 Induced by Doxorubicin.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4179-4179
Author(s):  
Yuping Gong ◽  
Xueshi Ye ◽  
Ting Liu
Keyword(s):  
Drug Resistance ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Drug ◽  
Leukemia Cell Line ◽  
Mdr1 Gene ◽  
Sensitive Cell ◽  
Single Factor ◽  
Efflux Rate ◽  
Sensitive Cell Line

Abstract Objective To study difference of drug-resistance between single-factor resistance cell line K562/MDR1 transfected with mdr1 gene and multi-factor resistance cell line K562/A02 induced by doxorubicin. Methods Retroviral virions carrying the complete sequence of mdr1 gene cDNA were produced and infected drug-sensitive leukemia cell line K562 and mdr1 single-factor resistance cell line K562/MDR1 was established. The difference of drug-resistance between K562/MDR1 and K562/A02, a kind of multi-factor resistance cell line induced by doxorubicin, was studied by checking the expression of mdr1 gene and Pgp, daunorubicin efflux rate, MTT drug sensitivity to chemotherapeutic drug. Lentiviral vector encoding shRNA which targeted MDR1 gene was transfected into two kinds of cell lines and effect of RNAi on reversing drug resistance was detected. Results The results of Q-PCR and flow cytometry demonstrated that there were high expression of mdr1 mRNA and Pgp in both kinds of drug-resistance cell lines and no difference between them. The function of Pgp detected by daunorubicin efflux rate is higher in K562/MDR1 (90.93%) than K562/A02 (78.67%). The results of MTT test showed that IC50 of K562/MDR1 and K562/A02 is 0.55 and 1.22μmol/L respectively and this confirmed that drug-resistance in K562/A02 is higher than that in K562/MDR1. After RNA interference, the expression of the mdr1 gene and Pgp in K562/MDR1 markedly was down-regulated and the drug resistance was restored and IC50 is 0.16μmol/L, similar to K562 sensitive cell line. The expression of the mdr1 gene and Pgp in K562/A02 markedly was downregulated too, and drug resistance to anticancer drug is reduced to some extent but IC50 is 0.56μmol/L, it is still higher than that in sensitive cell line. Conclusion Drug-resistance in K562/A02 induced by anticancer-drug was made of many factors and it is more resistance to anticancer-drug than that in K562/MDR1 caused by mdr1 gene. Due to only mdr1 resistance, K562/MDR1 is better cell model to make mdr1/Pgp research.

Low Expression of hOCT1 May Be a Key Point Mediating Low Intracellular Imatinib Accumulation in Imatinib Mesylate Resistance K562 Cell Line.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4547-4547
Author(s):  
Huanling Zhu ◽  
Ting Liu ◽  
Yongqian Jia
Keyword(s):  
Flow Cytometry ◽  
Cell Line ◽  
Real Time ◽  
Cell Lines ◽  
Real Time Pcr ◽  
K562 Cells ◽  
Pcr Analysis ◽  
Sensitive Cell ◽  
Imatinib Resistance ◽  
Low Expression

Abstract Objective To establish an imatinib resistance cell line and to study its resistant principia. Methods K562 cells were cultured in imatinib at gradually increased concentrations to generate their resistance cell line. Clone imatinib resistance cell lines by limited dilution culture. MTT assay, real time PCR and Semi-quantity PCR, flow cytometry and HPLC were used to clarify the possible mechanisms of the resistance. Results Imatinib resistance cell line K562R was successfully induced by continuous culture in the presence of gradually increasing doses of imatinib up to 5μmol/L. K562R cells were maintained in the media containing 5μmol/L imatinib. Proliferation data showed that cell growth of K562R was not inhibited in 5 μmol/L imatinib, whereas the parental sensitive cell was significantly inhibited by up to 2μM imatinib. The IC50 of K562R was about 7.5μmol/L which was ten times higher than that of the parental cell. HPLC revealed that the intracellular imatinib concentration of K562R was strikingly lower than that of the parental cells (up to 27.8-fold). MDR1 were not detected in mRNA (by RT-PCR)and protein(by flow cytometry) levels on K562R cell, whereas hOCT1 level measured by semi-quantity PCR showed lower expression in K562R cell lines than that of parental sensitive cell, indicating that low intracellular imatinib concentration may be due to lower affluence of imatinib by low level of hOCT1. (5) Real time PCR analysis showed no BCR-ABL/G6PD gene amplification and sequence analysis of the 374bp ABL kinase domain showed no mutation in K562R cell lines. Conclusion An imatinib resistance cell line K562R has been successfully established. Low expression of hOCT1 may be a key point mediating low intracellular imaitnib accumulation in K562R cell lines.

Novel Targeting Of Phospho-Marcks Overcomes Drug Resistance and Induces Anti-Tumor Activity In Preclinical Models Of Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 282-282 ◽  
Author(s):  
Yijun Yang ◽  
Manujendra N Saha ◽  
Yan Chen ◽  
Lugui Qiu ◽  
Donna E Reece ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Drug Resistance ◽  
Cell Lines ◽  
Research Funding ◽  
Resistant Cell ◽  
Drug Resistant ◽  
Sensitive Cell ◽  
Bortezomib Treatment ◽  
Cell Cycle Pathway ◽  
Rpmi 8226

Abstract Multiple myeloma (MM) remains incurable due to the development of a drug-resistant phenotype after prolonged therapy. Myristoylated alanine-rich C-kinase substrate (MARCKS) is a protein kinase C (PKC) substrate that plays an important role in cell adhesion, spreading and invasion. Our previous studies found that overexpression of phospho-MARCKS (pMARCKS) was detected in developed drug resistant MM cell lines (RPMI-8226 R5, MM.1R) relative to their parental drug sensitive cell lines (RPMI-8226S, MM.1S). We hypothesized that pMARCKS is involved in chemo- and novel drug resistance in MM. To further evaluate the drug resistance, we exposed both RPMI-8226 R5 and MM.1R cell lines to varying dosages of bortezomib, dexamethasone, doxorubicin, and lenalidomide. By MTT assay, both resistant cell lines were found to have significantly higher viability to all 4 drugs compared to their respective non-resistant lines. In addition, Western blot analysis showed increased pMARCKS expressions in all 3 bortezomib resistant cell lines 8226.BR, OPM2.BR, and ANBL-6.BR as compared to their respective bortezomib sensitive cell lines. We next acquired MM patient samples collected at diagnosis and at relapse after bortezomib treatment, and investigated their pMARCKS expression with immunoblotting analyses. The patient samples collected from relapse after bortezomib treatment had higher pMARCKS expression than those collected at diagnosis. Furthermore, we studied additional 3 primary MM patient samples with high pMARCKS expressions and 3 with low expressions for their vaibility after a 36 hour bortezomib treatment, and found that the samples with high pMARCKS expressions were more resistant to bortezomib than those with low pMARCKS expressions (mean IC50 of 7.1 nM and mean IC50 of 4.8 nM, respectively; p = 0.042). Importantly, combination of a low dosage of bortezomib (5.0 nM) with either 2.5 uM or 5.0 uM of enzastaurin (an inhibitor of phospho-PKC), displayed a synergistic cytotoxicity on myeloma cells with high pMARCKS expressions. To further elucidate the role of pMARCKS in drug resistance, we knocked down pMARCKS expression by transfecting siMARCKS into 8226 R5 and MM.1R cells. Following the knockdown, both cell lines had significantly lower viability after treatment with either bortezomib, dexamethasone, doxorubicin, or lenolidomide, in comparison to empty vector controls. FACS analysis and annexin V assay of the knockdown cells and the control cells from both cell lines showed significantly induction of G1/S cell cycle arrest and apoptosis in the knockdown cells. The immunoprecipitation (IP) and chromatin immunoprecipitation (ChIP) DNA-qPCR analysis further demonstrated that pMARCKS regulates SKP2 expression through binding with E2F1, mediating SKP2/p27Kip1 cell cycle pathway. Finally, we investigated the effect of inhibition of pMARCKS in a 8226 R5 xenograft model of SCID mice. Mice injected with shMARCKS-transfected 8226 R5 cells and received bortezomib showed significant retardation of tumor growth and prolonged survival compared to the control groups. Taken together, our data indicate that pMARCKS is constitutively activated in resistant and relapsed MM cells and contributes to drug resistance by regulating E2F1 mediated SKP2/p27Kip1 cell cycle pathway, thus providing a preclinical rationale for targeting pMARCKS as a promising approach in patients with refractory/relapsed MM. Disclosures: Reece: BMS: Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Millennium: Research Funding; Novartis: Honoraria; Onyx: Honoraria.

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