Life Sciences Commons^™

Cancer Cell Population Growth Kinetics At Low Densities Deviate From The Exponential Growth Model And Suggest An Allee Effect., Kaitlyn E Johnson, Grant Howard, William Mo, Michael K Strasser, Ernesto A B F Lima, Sui Huang, Amy Brock

Articles, Abstracts, and Reports

Most models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale positively with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect. In preclinical and clinical models, however, tumor growth data are limited by the …

Linkage, Whole Genome Sequence, And Biological Data Implicate Variants In Rab10 In Alzheimer's Disease Resilience., Perry G Ridge, Celeste M Karch, Simon Hsu, Ivan Arano, Craig C Teerlink, Mark T W Ebbert, Josue D Gonzalez Murcia, James M Farnham, Anna R Damato, Mariet Allen, Xue Wang, Oscar Harari, Victoria M Fernandez, Rita Guerreiro, Jose Bras, John Hardy, Ronald Munger, Maria Norton, Celeste Sassi, Andrew Singleton, Steven G Younkin, Dennis W Dickson, Todd E Golde, Nathan D Price, Nilüfer Ertekin-Taner, Carlos Cruchaga, Alison M Goate, Christopher Corcoran, Joann Tschanz, Lisa A Cannon-Albright, John S K Kauwe

Articles, Abstracts, and Reports

BACKGROUND: While age and the APOE ε4 allele are major risk factors for Alzheimer's disease (AD), a small percentage of individuals with these risk factors exhibit AD resilience by living well beyond 75 years of age without any clinical symptoms of cognitive decline.

METHODS: We used over 200 "AD resilient" individuals and an innovative, pedigree-based approach to identify genetic variants that segregate with AD resilience. First, we performed linkage analyses in pedigrees with resilient individuals and a statistical excess of AD deaths. Second, we used whole genome sequences to identify candidate SNPs in significant linkage regions. Third, we replicated SNPs …

Modulation Of Bax And Mtor For Cancer Therapeutics., Rui Li, Chunyong Ding, Jun Zhang, Maohua Xie, Dongkyoo Park, Ye Ding, Guo Chen, Guojing Zhang, Melissa Gilbert-Ross, Wei Zhou, Adam I Marcus, Shi-Yong Sun, Zhuo G Chen, Gabriel L Sica, Suresh S Ramalingam, Andrew T Magis, Haian Fu, Fadlo R Khuri, Walter J Curran, Taofeek K Owonikoko, Dong M Shin, Jia Zhou, Xingming Deng

Articles, Abstracts, and Reports

A rationale exists for pharmacologic manipulation of the serine (S)184 phosphorylation site of the proapoptotic Bcl2 family member Bax as an anticancer strategy. Here, we report the refinement of the Bax agonist SMBA1 to generate CYD-2-11, which has characteristics of a suitable clinical lead compound. CYD-2-11 targeted the structural pocket proximal to S184 in the C-terminal region of Bax, directly activating its proapoptotic activity by inducing a conformational change enabling formation of Bax homooligomers in mitochondrial membranes. In murine models of small-cell and non-small cell lung cancers, including patient-derived xenograft and the genetically engineered mutant KRAS-driven lung cancer models, CYD-2-11 …