Protein kinase 2 (CK2): a potential regulator of immune cell development and function in cancer.

Protein kinase CK2, formally known as casein kinase II, is ubiquitously expressed and highly conserved serine/threonine or tyrosine kinase enzyme that regulates diverse signaling pathways responsible for cellular processes (i.e., cell proliferation and apoptosis) via interactions with over 500 known substrates. The enzyme's physiological interactions and cellular functions have been widely studied, most notably in the blood and solid malignancies. CK2 has intrinsic role in carcinogenesis as overexpression of CK2 subunits (α, α`, and ß) and deregulation of its activity have been linked to various forms of cancers. CK2 also has extrinsic role in cancer stroma or in the tumor microenvironment (TME) including the immune cells. However, very few research studies have focused on extrinsic role of CK2 in regulating immune responses as a therapeutic alternative for cancer. The following review discusses CK2's regulation of key signaling events [Nuclear factor kappa B (NF-κB), Janus kinase/signal transducer and activators of transcription (JAK/STAT), Hypoxia inducible factor-1alpha (HIF-1α), Cyclooygenase-2 (COX-2), Extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK), Notch, Protein kinase B/AKT, Ikaros and Wnt] that can influence the development and function of immune cells in cancer. Potential clinical trials using potent CK2 inhibitors will facilitate and improve the treatment of human malignancies.

Understanding hormone and hormone therapies' impact on the auditory system.

Hormones such as estrogen, progesterone, and aldosterone all demonstrate vital roles in sustaining auditory function through either the maintenance of cochlear neurons, up/down regulation of critical molecules (i.e., IGF-1, BDNF, etc.), or generation of the endocochlear potential. With disease and/or age, hormone expression begins to decline drastically, which ultimately affects cochlear structures and the integrity of cochlear cells. The following review explores the latest findings as well as realistic outcomes for hormone therapy treatment in the auditory system. This information could serve as a potential guide for patients considering hormone therapy as a medicinal choice to alleviate the signs of onset of presbycusis-age-related hearing loss. Additional scientific investigations could also be carried out to further enhance recent findings.

Hormone replacement therapy attenuates hearing loss: Mechanisms involving estrogen and the IGF-1 pathway.

Estradiol (E) is a multitasking hormone that plays a prominent role in the reproductive system, and also contributes to physiological and growth mechanisms throughout the body. Frisina and colleagues have previously demonstrated the beneficial effects of this hormone, with E-treated subjects maintaining low auditory brainstem response (ABR) thresholds relative to control subjects (Proceedings of the National Academy of Sciences of the United States of America, 2006;103:14246; Hearing Research, 2009;252:29). In the present study, we evaluated the functionality of the peripheral and central auditory systems in female CBA/CaJ middle-aged mice during and after long-term hormone replacement therapy (HRT) via electrophysiological and molecular techniques. Surprisingly, there are very few investigations about the side effects of HRT in the auditory system after it has been discontinued. Our results show that the long-term effects of HRT are permanent on ABR thresholds and ABR gap-in-noise (GIN) amplitude levels. E-treated animals had lower thresholds and higher amplitude values compared to other hormone treatment subject groups. Interestingly, progesterone (P)-treated animals had ABR thresholds that increased but amplitude levels that remained relatively the same throughout treatment. These results were consistent with qPCR experiments that displayed high levels of IGF-1R in the stria vascularis (SV) of both E and P animal groups compared to combination treatment (E + P) animals. IGF-1R plays a vital role in mediating anti-apoptotic responses via the PI3K/AKT pathway. Overall, our findings gain insights into the neuro-protective properties of E hormone treatments as well as expand the scientific knowledge base to help women decide whether HRT is the right choice for them.

Auditory brainstem gap responses start to decline in mice in middle age: a novel physiological biomarker for age-related hearing loss.

The auditory function of the CBA/CaJ mouse strain is normal during the early phases of life and gradually declines over its lifespan, much like human age-related hearing loss (ARHL) but within the "time frame" of a mouse life cycle. This pattern of ARHL is similar to that of most humans: difficult to diagnose clinically at its onset and currently not treatable medically. To address the challenge of early diagnosis, we use CBA mice to analyze the initial stages and functional onset biomarkers of ARHL. The results from Auditory Brainstem Response (ABR) audiogram and Gap-in-noise (GIN) ABR tests were compared for two groups of mice of different ages, namely young adult and middle age. ABR peak components from the middle age group displayed minor changes in audibility but had a significantly higher prolonged peak latency and decreased peak amplitude in response to temporal gaps in comparison with the young adult group. The results for the younger subjects revealed gap thresholds and recovery rates that were comparable with previous studies of auditory neural gap coding. Our findings suggest that age-linked degeneration of the peripheral and brainstem auditory system begins in middle age, allowing for the possibility of preventative biomedical or hearing protection measures to be implemented in order to attenuate further damage to the auditory system attributable to ARHL.