Combining old and new concepts in targeting telomerase for cancer therapy: transient, immediate, complete and combinatory attack (TICCA).

Telomerase can overcome replicative senescence by elongation of telomeres but is also a specific element in most cancer cells. It is expressed more vastly than any other tumor marker. Telomerase as a tumor target inducing replicative immortality can be overcome by only one other mechanism: alternative lengthening of telomeres (ALT). This limits the probability to develop resistance to treatments. Moreover, telomerase inhibition offers some degree of specificity with a low risk of toxicity in normal cells. Nevertheless, only one telomerase antagonist reached late preclinical studies. The underlying causes, the pitfalls of telomerase-based therapies, and future chances based on recent technical advancements are summarized in this review. Based on new findings and approaches, we propose a concept how long-term survival in telomerase-based cancer therapies can be significantly improved: the TICCA (Transient Immediate Complete and Combinatory Attack) strategy.

Influence of exposure to pesticides on telomere length and pregnancy outcome: Diethylphosphates but not Dimethylphosphates are associated with accelerated telomere attrition in a Palestinian cohort.

Exposure to environmental pesticides during pregnancy is associated with adverse health outcomes such as low birth weight and impaired neuro-development. In this study, we assessed maternal leukocyte telomere lengths (TL) in Palestinian pregnant women and compared the data with urinary organophosphate concentrations, demographic, lifestyle and dietary factors, birth weight, body length, gestational age, and head circumference. Women with high urine levels of creatinine adjusted diethylphosphate(DE)derived pesticide metabolites DEP, DETP or DEDTP had shorter telomeres (p = 0.05). Women living in proximity to agricultural fields had shorter telomeres compared to women not living in proximity to agricultural fields (p = 0.011). Regular consumption of organic food was associated with shorter telomeres (p = 0.01), whereas the consumption of other vegetables such as artichokes was rather associated with longer telomeres. By contrast, urine levels of dimethylphosphate(DM)-derived pesticide metabolites DMTP and DMDTP were associated with lower birth weight (p = 0.05) but not with shrter telomeres. In conclusion organophosphate pesticides and living in proximity to agriculture are associated with shorter TL, likely due to higher consumption of contaminated fruits and vegetables and/or the transport of pesticides to non-treatment sites. DE and DM substituted pesticides seem to have different effects on telomeres and development.