Novel adamantyl retinoid-related molecules with POLA1 inhibitory activity

Article abstract of DOI:10.1016/j.bioorg.2020.104253

Atypical retinoids (AR) or retinoid-related molecules (RRMs) represent a promising class of antitumor compounds. Among AR, E-3-(3′-adamantan-1-yl-4′-hydroxybiphenyl-4-yl)acrylic acid (adarotene), has been extensively investigated. In the present work we report the results of our efforts to develop new adarotene-related atypical retinoids endowed also with POLA1 inhibitory activity. The effects of the synthesized compounds on cell growth were determined on a panel of human and hematological cancer cell lines. The most promising compounds showed antitumor activity against several tumor histotypes and increased cytotoxic activity against an adarotene-resistant cell line, compared to the parent molecule. The antitumor activity of a selected compound was evaluated on HT-29 human colon carcinoma and human mesothelioma (MM487) xenografts. Particularly significant was the in vivo activity of the compound as a single agent compared to adarotene and cisplatin, against pleural mesothelioma MM487. No reduction of mice body weight was observed, thus suggesting a higher tolerability with respect to the parent compound adarotene.

Full text of DOI:10.1016/j.bioorg.2020.104253

January 2017
Abstracts
S461
5%, 7%, 9%, and 11%; and differed significantly by
smoking status (p¼0.0539, p¼0.0316, p¼0.0187,
p¼0.0017). At 5 years, overall survival was 69% for
never smokers, 55% for active, and 49% for former
smokers (p¼0.0002) (Figure 1). Controlling for age, sex,
race, insurance, histologic grade, extent of resection, and
length of surgery, and compared with never smokers,
active smokers had 1.3 times (p¼0.05) the hazard of
death and former smokers had 1.4 times the hazard of
death (p¼0.04).
Conclusion: Overall, Our findings suggest that catechin
hydrate inhibits B(a)P-induced lung tumor formation by
modulating hyperproliferation, inflammation, apoptosis
and ALDH1 expression.
Keywords: Catechin hydrate, aldehyde dehydrogenase
1, carcinoembryonic antigen, chemoprevention
P1.01-021
The Impact of Smoking Status on
Overall Survival in a Population-Based
Non-Small Cell Lung Cancer (NSCLC)
Surgical Resection Cohort
Topic: Protective Factors, Risk Reduction,
Smoking Cessation
Nicholas Faris,1 Yu-Sheng Lee,2 Meghan Meadows,2
Matthew Smeltzer,2 Meredith Ray,2 Kenneth Ward,2
Carrie Fehnel,1 Cheryl Houston-Harris,3
Raymond Osarogiagbon3 1Thoracic Oncology Research
Group, Multidisciplinary Thoracic Oncology Program,
Baptist Cancer Center, Memphis/TN/United States of
2
America, School of Public Health, University of Memphis,
3
Memphis/TN/United States of America, Thoracic
Oncology Research Group, Multidisciplinary Thoracic
Oncology Program, Baptist Cancer Center, Memphis/
United States of America
Conclusion: In this population-based cohort, smoking is
negatively associated with post-operative mortality and
long-term overall patient survival; although active
smokers had better survival outcomes than former
smokers.
Background: Surgical resection is the optimal treat-
ment modality for NSCLC, while smoking has been
shown to have a negative survival impact. We evalu-
ated smoking’s impact on overall survival within a
population-based cohort of patients with surgically-
resected NSCLC.
Keywords: non-small cell lung cancer, Surgical resec-
tion, survival, tobacco control and cessation
Methods: We examined all patients who had a curative-
intent NSCLC resection from 2009-2016 in 4 contiguous
Dartmouth Hospital Referral Regions of the US. We
compared patient and clinical characteristics among
never, former (stopped ꢀ1 year prior), and active
smokers using the Chi-square and ANOVA tests. Survival
analyses were conducted with the Kaplan-Meier method
and Cox Proportional Hazards models.
P1.01-022
Smoking Cessation Related to Lung
Resection
Topic: Protective Factors, Risk Reduction,
Smoking Cessation
Results: Of 2,202 patients, 206 (9%) were never, 846
(38%) were former, and 1,150 (52%) were active
smokers. Significant demographic and clinical differ-
ences between cohorts included age, sex, race, insurance,
comorbidities, pulmonary function, method of detection,
ASA status, extent, primary site and length of resection,
histology, and histologic grade (all pꢁ0.05). Short-term
post-operative mortality (at 30-, 60-, 90-, 120-days)
rates for never smokers were 1%, 2%, 4%, 4%; for active
smokers, 4%, 6%, 7% and 8%; and for former smokers,
Bruno Sarana,1 Indrek Benno,1 Piret Kibur,1
Ragnar Toomas Kibur,2 Triin Kütt,2 Mait Raag,3
Tanel Laisaar1 1Thoracic Surgery Department,
2
Tartu University, Tartu/Estonia, Tartu University,
3
Tartu/Estonia, Public Health, Tartu University,
Tartu/Estonia
Background: Smoking cessation interventions are often
ineffective, although negative health effects of smoking