Browsing Over 138 Presentations
34P - Impact of treatment with bilastine for PD-1/PD-L1 inhibitors induced rash (ID 125)
- T. Hirata
- T. Hirata
Abstract
Background
PD-1/PD-L1 inhibitors are novel anti-cancer agents for various tumors. PD-1/PD-L1 inhibitors induced rash occurred in 20% to 30%. The therapy for rash includes anti-histamine and corticosteroid. Bilastine is a non-sedating second-generation H1-antihistamine. Bilastine showed the efficacy for urticaria, prurigo and cutaneous pruritus. However, its effectiveness for PD-1/PD-L1 inhibitors induced rash is unknown. The objective of this retrospective study was to evaluate the efficacy of bilastine for PD-1/PD-L1 inhibitors induced rash.
Methods
We identified 224 patients who received PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, atezolizumab) at the Kure Medical Center from September 2014 to October 2018. PD-1/PD-L1 inhibitors induced rashes were observed in 84 patients (37.5%). They were classified into 4 groups on the basis of the systemic antihistamine and topical corticosteroid therapy: the (1) bilastine and corticosteroid group (n = 18), (2) another anti-histamine and corticosteroid group (n = 22), (3) bilastine group (n = 20); and (4) another antihistamine group (n = 24). Adverse events were graded according to the Common Terminology Criteria for Adverse Events (version 4.0). This study was approved by the Kure Medical Center IRB.
Results
The bilastine and corticoegsteroid group had significantly shorter the median duration of topical corticosteroids and antihistamine than the another antihistamine and corticosteroid group (p<0.01). Bilastine group had significantly shorter the period of systemic medications than the another antihistamine group (p<0.01). The incidence of adverse events was observed as follows, somnolence in 3% (1/38), headache 3% (1/38) and dizziness in 3% (1/38) in the bilastine and corticosteroid group and bilastine group. There were no serious adverse events.
Conclusions
Bilastine treatment reduced the need for topical corticosteroids use and shortened the period of topical corticosteroids for PD-1/PD-L1 inhibitors induced rash with acceptable safety profiles. Bilastine may be more effective than another antihistamine for PD-1/PD-L1 inhibitors induced rash.
Legal entity responsible for the study
Taizo Hirata.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.
35P - Enhancement of high-LET radiation-induced lung cancer cell apoptosis by Antennapedia proteins (ANTP)-SmacN7 (ID 139)
- Y. Xie
- Y. Xie
Abstract
Background
The aim of the present study was to investigate the mechanisms underlying the radiation-sensitising effect from antennapedia proteins (ANTP)-SmacN7 on induction of apoptosis in lung cancer cells irradiated with high-LET ionizing irradiation (IR) from accelerated carbon and iron particles.
Methods
Two cultured human non-small lung cancer (NSCLC) cell lines, A549 and NCI-H460, were irradiated with low-LET X-irradiations or high-LET IR with or without treatment of ANTP-SmacN7. Change of cell survival, induction of apoptosis and cell cycle progression, and alterations in both death and survival signals for apoptosis, were studied by colony formation assay, flowcytometry, and Western blot analysis, respectively.
Results
Showed that at the LD50 for clonogenic cell killing by high-LET iron particles, compared to the low-LET X-rays irradiations, high-LET IR was more efficient for clonogenic cell killing and induction of apoptosis, which was correlated with cell G2/M phase progression. In addition, ANTP-SmacN7 markedly promoted apoptotic cell killing through inhibition of X-linked inhibitor of apoptosis protein (XIAP) and activation of caspase-3 and 9. Furthermore, both antiapoptotic and proapoptotic molecular response was correlated with the apoptotic cell killing and in accordance with the results of clonogenic cell killing.
Conclusions
These findings provide useful information to contribute to the improvement of high-LET clinical radiotherapy for NSCLC from the point of view of pharmaceutical radio-sensitization.
Legal entity responsible for the study
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, PRC.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.
36P - Structural diversity of the cardenolide calotropin renders it as a targeted therapy for harnessing TNBC progression through tuning nitric oxide (NO) levels (ID 183)
- R. Ellayeh
- R. Ellayeh
- R. Youness
- H. Askary
- A. Abdelmotaal
- R. Assal
Abstract
Background
Triple negative breast cancer (TNBC) is the most aggressive breast cancer (BC) subtype. It has the worst prognosis, highest recurrence and metastatic rates. Due to the clinical and molecular heterogeneity of TNBC, there is an emerging need to identify new molecular therapeutic targets. Nitric oxide (NO) has a dual role in cancer depending on its levels. At low concentrations, NO promotes tumor growth, while at high concentrations, NO has an anti-neoplastic function. Natural compounds have emerged as signaling pathways’ regulators in various tumors. Cardenolides specifically have potent cytotoxic effects in different cancers as lung and liver cancer. Our group has isolated the cardenolides, Calotropin and 7,8-dehydrocalotropin from Calotropisgigantea (L.) Dryand (Apocyanaceae). Calotropin showed potent cytotoxicy against non-small cell lung cancer, glioblastoma and prostate cancer, but has never been investigated against BC. Our aim was to investigate the anticancer effects of the isolated compounds on MDA-MB-231 TNBC cells by functional characterization and unravel their role in regulating NO levels in BC.
Methods
MDA-MB-231 cells were treated with serial dilutions (1, 5, 10, 20, 60 and 100 μM) of calotropin and 7,8-dehydrocalotropin. Their cytotoxic activities were assessed using MTT for cellular viability and IC50 values were obtained. Cellular migration and colony forming ability were measured using scratch and colony forming assays, respectively. NO production was measured using Greiss reagent.
Results
Both calotropin and 7,8-dehydrocalotropin were able to decrease cellular viability, migration and colony formation of MDA-MB-231 cells in a dose-dependent manner. Calotropin reduced NO levels in MDA-MB-231 cells. However 7,8-dehydrocalotropin did not have any significant effects in regulating NO.
Conclusions
Calotropin showed more potent cytotoxicity on MDA-MB-231 cells compared to 7,8-dehydrocalotropin. Calotropin acts as a negative regulator of NO production, whereas 7,8-dehydrocalotropin failed to regulate NO production. This could be attributed to the structural difference between both compounds. Thus calotropin can be developed as a targeted therapy against BC.
Legal entity responsible for the study
German University of Cairo.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
37P - Genomics and pharmacogenomics analyses of cancer cell lines using the CellMinerCDB and CellMiner web-applications (ID 168)
- W. Reinhold
- W. Reinhold
- Y. Pommier
Abstract
Background
Complimentary datasets and functionality that facilitate comparisons of genomic, molecular and pharmacological data within the NCI-60 cancerous cell lines, Cancer Cell Line Encyclopedia (CCLE), Genomics of Drug Sensitivity in Cancer (GDSC), Cancer Therapeutics Response Portal (CTRP), NCI/DTP small cell lung cancer (SCLC), and NCI Almanac cell line sets are provided by the CellMiner (
Methods
Pharmacogenomics analyses using CellMiner compare the 60 cancerous cell lines of the NCI-60 using five tools, and include 22 data sets. Pharmacogenomics analyses using CellMinerCDB compare the NCI-60, CCLE, GDSC, CTRP, NCI/DTP SCLC, and NCI Almanac cell line data six, using eight tools, and include 29 data sets. Both provide multiple ways to download or query that data, and are described in detail in their respective urls.
Results
Data for the NCI-60, providing the most extensive public set of cell line molecular and drug activity data (generated by the NCI Developmental Therapeutics Program
Conclusions
Exploration of the relationships between and among molecular alterations and pharmacological responses in cancer cell lines from the omic perspective is facilitated by this rich set of data and functionalities.
Legal entity responsible for the study
The National Cancer Institute, USA.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Cancer evolution as a therapeutic target (ID 111)
- A. Bardelli
- A. Bardelli
Introduction (ID 11)
- R. Plummer
- R. Plummer
DNA polymerase Theta (POLθ) as an anticancer target (ID 12)
- G. Higgins
- G. Higgins
Targeting the WNT pathway for cancer therapy (ID 13)
- D. Tan
- D. Tan
Clinical development of oxidative phosphorylation (OXPHOS) inhibitors (ID 14)
- T. Yap
- T. Yap
HIF-2a (ID 15)
- E. Jonasch
- E. Jonasch