Exploring the origin of the cancer stem cell niche and its role in anti-angiogenic treatment for glioblastoma.

Cancer stem cells are thought to be the main drivers of tumorigenesis for malignancies such as glioblastoma (GBM). They are maintained through a close relationship with the tumor vasculature. Previous literature has well-characterized the components and signaling pathways for maintenance of this stem cell niche, but details on how the niche initially forms are limited. This review discusses development of the nonmalignant neural and hematopoietic stem cell niches in order to draw important parallels to the malignant environment. We then discuss what is known about the cancer stem cell niche, its relationship with angiogenesis, and provide a hypothesis for its development in GBM. A better understanding of the mechanisms of development of the tumor stem cell niche may provide new insights to potentially therapeutically exploit.

Paced Mating Behaviour Is Influenced by Duration of Female Post-Ejaculatory Interval.

BACKGROUND: Laboratory paradigms that enable the female rat to control the frequency and temporal distribution of sexual stimulation are well-suited to gaining knowledge about female sexual function; however, the variety of procedures used influence the specific behaviors exhibited by female rats and bring uncertainty into the conclusions that can be drawn. AIM: In this study, we evaluated the effects of test parameters on the display of paced mating behavior in female rats to develop better preclinical models for exploring female sexual health. METHODS: Sexually experienced, estradiol- and progesterone-primed female rats were tested under paced mating conditions to determine whether sexual behavior differed as a function of number of male partners (1 or 3; Experiment 1), the time span between receipt of an ejaculation and the next intromission (ie, the post-ejaculatory interval or PEI; Experiment 2), or the duration of ejaculations (Experiment 3). OUTCOMES: Contact-return latency, exit latency, and withdrawal duration after mounts, intromissions, and ejaculations. RESULTS: The shorter withdrawal latency after intromission and longer return latency after ejaculation observed in 30-minute paced mating tests is best attributed to the female's PEI. The duration of the PEI is a specific factor that affects the display of paced mating behavior. CLINICAL TRANSLATION: Understanding of neurobiological mechanisms and sensory factors influencing sexual behavior learned from these models can be applied to studies of human female sexual health. STRENGTHS & LIMITATIONS: Sexual motivation is indicated by analogous behaviors and supported by evolutionarily conserved systems in women and rats, meaning that animal models can be used to identify neurobiological mechanisms subserving these behaviors. Nonetheless, data related specifically to physiological effects of different mating paradigms are needed in future research. CONCLUSION: Procedures that mimic naturalistic settings, and thus enable female sexual motivation to drive behavior, are apt for studies aimed at understanding mechanisms supporting female sexual function whereas artificially lengthening the interval between an ejaculation and subsequent intromission may provide a model to study female sexual dysfunction. Corlett AG, Frankl PR, Akindona FAB, et al. Paced Mating Behaviour Is Influenced by Duration of Female Post-Ejaculatory Interval. J Sex Med 2022;19:1506-1516.