scholarly journals Heat Shock Protein Inhibitor 17-Allyamino-17-Demethoxygeldanamycin, a Potent Inductor of Apoptosis in Human Glioma Tumor Cell Lines, Is a Weak Substrate for ABCB1 and ABCG2 Transporters

2021 ◽  
Vol 14 (2) ◽  
pp. 107
Author(s):  
Nikola Pastvova ◽  
Petr Dolezel ◽  
Petr Mlejnek
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Tumor Cell ◽  
Cell Lines ◽  
Single Agent ◽  
Heat Shock Protein 90 ◽  
Genetic Alterations ◽  
Tumor Cell Lines ◽  
Cytotoxic Effects ◽  
Glioma Tumor

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and has a poor prognosis. Complex genetic alterations and the protective effect of the blood–brain barrier (BBB) have so far hampered effective treatment. Here, we investigated the cytotoxic effects of heat shock protein 90 (HSP90) inhibitors, geldanamycin (GDN) and 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin), in a panel of glioma tumor cell lines with various genetic alterations. We also assessed the ability of the main drug transporters, ABCB1 and ABCG2, to efflux GDN and 17-AAG. We found that GDN and 17-AAG induced extensive cell death with the morphological and biochemical hallmarks of apoptosis in all studied glioma cell lines at sub-micro-molar and nanomolar concentrations. Moderate efflux efficacy of GDN and 17-AAG mediated by ABCB1 was observed. There was an insignificant and low efflux efficacy of GDN and 17-AAG mediated by ABCG2. Conclusion: GDN and 17-AAG, in particular, exhibited strong proapoptotic effects in glioma tumor cell lines irrespective of genetic alterations. GDN and 17-AAG appeared to be weak substrates of ABCB1 and ABCG2. Therefore, the BBB would compromise their cytotoxic effects only partially. We hypothesize that GBM patients may benefit from 17-AAG either as a single agent or in combination with other drugs.

Activation of the heat shock transcription factor by hypoxia in normal and tumor cell lines in vivo and in vitro

1992 ◽  
Vol 23 (4) ◽  
pp. 891-897 ◽  
Author(s):  
Amato J. Giaccia ◽  
Elizabeth A. Auger ◽  
Albert Koong ◽  
David J. Terris ◽  
Andrew I. Minchinton ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Tumor Cell ◽  
Cell Lines ◽  
Heat Shock Transcription Factor ◽  
Tumor Cell Lines

Cytotoxic Effects of 24/R,25-Dihydroxycholecalciferol on the Proliferation of Various Tumor Cell Lines in vitro and Its Antitumor Effects in vivo

Oncology ◽  
1988 ◽  
Vol 45 (3) ◽  
pp. 206-209 ◽  
Author(s):  
Yuji Maeda ◽  
Tohru Hirai ◽  
Hideyuki Yamato ◽  
Noriko Kobori ◽  
Ken-ichi Matsunaga ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Tumor Cell Lines ◽  
Antitumor Effects ◽  
Cytotoxic Effects

scholarly journals Erratum to “Cell-Type-Dependent Thyroid Hormone Effects on Glioma Tumor Cell Lines”

2012 ◽  
Vol 2012 ◽  
pp. 1-1
Author(s):  
Alexandros Liappas ◽  
Iordanis Mourouzis ◽  
Athanasios Zisakis ◽  
Konstantinos Economou ◽  
Robert-William Lea ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Tumor Cell ◽  
Cell Lines ◽  
Tumor Cell Lines ◽  
Cell Type ◽  
Hormone Effects ◽  
Glioma Tumor

scholarly journals STI571 (Glivec) inhibits the interaction between c-KIT and heat shock protein 90 of the gastrointestinal stromal tumor cell line, GIST-T1

2005 ◽  
Vol 96 (2) ◽  
pp. 116-119 ◽  
Author(s):  
Hajime Nakatani ◽  
Michiya Kobayashi ◽  
Toufeng Jin ◽  
Takahiro Taguchi ◽  
Takeki Sugimoto ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Tumor Cell ◽  
Gastrointestinal Stromal Tumor ◽  
Cell Line ◽  
Tumor Cell Line ◽  
Heat Shock Protein 90 ◽  
Stromal Tumor

Activity of the heat shock protein 90 (HSP90) inhibitor, SNX-2112, in pediatric cancer cell lines.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 9565-9565
Author(s):  
D. C. Chinn ◽  
W. S. Holland ◽  
J. M. Yoon ◽  
T. Zwerdling ◽  
P. C. Mack
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pediatric Cancer ◽  
Heat Shock Protein 90 ◽  
Cancer Cell Lines ◽  
Hsp90 Inhibitor

A randomized study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel versus docetaxel alone for second-line therapy of lung adenocarcinoma (GALAXY-1).

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. CRA8007-CRA8007 ◽  
Author(s):  
Suresh S. Ramalingam ◽  
Glenwood D. Goss ◽  
Zoran Gojko Andric ◽  
Igor Bondarenko ◽  
Bojan Zaric ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Lung Adenocarcinoma ◽  
Biological Effects ◽  
Single Agent ◽  
Heat Shock Protein 90 ◽  
Phase Iii ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

CRA8007 Background: Heat shock protein 90 chaperone function is critical for the biological effects of several oncoproteins. Ganetespib (G) is a highly potent 2nd-generation Hsp90 inhibitor with a favorable safety profile and single-agent clinical activity. Methods: Based on synergistic preclinical interactions between docetaxel (D) and G, we conducted a randomized (1:1), international open-label study of D with or without G. Patients with advanced lung adenocarcinoma, one prior systemic therapy, and ECOG PS 0/1 were included. D was given at 75 mg/m2 on day 1 of a three-week cycle. In the experimental arm, D was given on day 1 and G at 150 mg/m2 on days 1 and 15. The co-primary endpoints were PFS in patients with elevated LDH (eLDH) levels, or tumors harboring KRAS mutations. Key secondary endpoints were OS and PFS in all adenocarcinoma patients. Target enrollment was 240 adenocarcinoma, 120 eLDH, and 80 mKRAS patients. Statistical tests are 1-sided. Results: Enrollment of 255 adenocarcinoma patients completed in November 2012; results are reported for this population. Patient characteristics were balanced (median age 60 years, males ~60%, PS 0 ~40% and never-smoker ~25%). For D+G vs. D the median number of cycles delivered was 5 vs. 4; the grade 3/4 adverse events were neutropenia 38% vs. 37%; fatigue 4% vs. 3%; anemia 7% vs. 6%; diarrhea 3% vs. 0; fever with neutropenia 8% vs. 2%. At the time of abstract submission OS HR was 0.69 (90% CI 0.48 to 0.99, p=0.093), the PFS HR was 0.70 (90% CI 0.53 to 0.94, p=0.012), and the ORR was 15% vs 11%, favoring D+G. For patients that were enrolled >6 months after diagnosis of advanced NSCLC (N=175; 69%), a prespecified stratification factor, the OS HR was 0.41 (90% CI 0.25 to 0.67, p=0.0009), the PFS HR was 0.47 (90% CI 0.32 to 0.69, p=0.0005), and the ORR was 16% vs 12%. Updated results for both populations above, as well as for the eLDH and mKRAS subsets, will be presented. Conclusions: D+G demonstrated improvement in OS, PFS, and ORR over D alone for second-line therapy of lung adenocarcinoma. A phase III study in second-line advanced adenocarcinoma patients (> 6 months from diagnosis) is ongoing (GALAXY-2). Clinical trial information: NCT01348126.

Efficacy markers for cisplatin and S-1 in biliary tract carcinoma.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 334-334
Author(s):  
Yasunari Sakamoto ◽  
Hidenori Ojima ◽  
Chigusa Morizane ◽  
Seri Yamagishi ◽  
Hiroko Hosoi ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Biliary Tract ◽  
Mtt Assay ◽  
Biliary Tract Carcinoma ◽  
Tumor Cell Lines ◽  
Cytotoxic Effects ◽  
First Choice ◽  
Ercc1 Expression ◽  
Mtt Assays

334 Background: Gemcitabine (GEM) + cisplatin (CDDP) combination chemotherapy is the first choice for advanced biliary tract carcinoma (BTC). In Japan, the GEM + S-1 therapy has shown promise for the treatment of BTC. Our aim was to investigate the cytotoxic effects of GEM, CDDP and S-1 on BTC cell lines and find an immunohistochemical marker for predicting the efficacy of chemotherapy. Methods: We evaluated the efficacy of GEM, CDDP, and S-1 by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of 17 BTC cell lines. Furthermore, we subdivided the cell lines into sensitive and insensitive groups on the basis of the sensitivity of each drug. Moreover, pairwise studies were conducted using the MTT assay, Bliss additivism model, and Combination Index for analysis. Immunohistochemical expression analysis of excision repair cross-complementation group 1 (ERCC1), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), and thymidine phosphorylase (TP) were also performed in each cell line to compare the results of the cytotoxic effects of CDDP and S-1. Results: In the single-agent MTT assays, among the 17 tumor cell lines, 11 were sensitive to GEM, 13 to CDDP, and 11 to S-1. In 5 cell lines, <30% of the cells showed ERCC1 expression; these lines belonged to the CDDP-sensitive group. Conversely, the cell lines with >30% ERCC1-positive cells mostly belonged to the CDDP-insensitive group. CDDP IC50 correlated with the percentage of ERCC1-positive cells (P <.05). In contrast, none of the immunohistochemical markers could be used to select a cutoff level that would point to the sensitivity to S-1. In pairwise MTT assays (combination therapy), we demonstrated the synergy of GEM with CDDP in 9 tumor cell lines (53%) and the synergy of GEM with S-1 in 4 tumor cell lines(24%). Although 3 cell lines with the synergy of GEM with CDDP showed <30% ERCC1-positive cells, there was no correlation between them. Conclusions: ERCC1 expression in <30% of cells may help to identify CDDP-sensitive tumors; however, it is unknown whether expression of ERCC1 can help to predict efficacy of treatment with GEM + CDDP.

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