Chihiro Miwa

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates cell growth and metabolism in response to diverse external stimuli. In the presence of mitogenic stimuli, mTOR transduces signals that activate the translational machinery and promote cell growth. mTOR functions as a central node in a complex net of signaling pathways that are involved both in normal physiological, as well as pathogenic events. mTOR signaling occurs in concert with upstream Akt and tuberous sclerosis complex (TSC) and several downstream effectors. During the past few decades, the mTOR-mediated pathway has been shown to promote tumorigenesis through the coordinated phosphorylation of proteins that directly regulate cell-cycle progression and metabolism, as well as transcription factors that regulate the expression of genes involved in the oncogenic processes. The importance of mTOR signaling in oncology is now widely accepted, and agents that selectively target mTOR have been developed as anti-cancer drugs. In this review, we highlight the past research on mTOR, including clinical and pathological analyses, and describe its molecular mechanisms of signaling, and its roles in the physiology and pathology of human diseases, particularly, lung carcinomas. We also discuss strategies that might lead to more effective clinical treatments of several diseases by targeting mTOR.

To clarify the role of autonomic nervous functions in cardiovascular adaptation to microgravity, heart rate variability (HRV) and blood pressure variability (BPV) were evaluated during thermoneutral head-out water immersion (HOI) of eight healthy young subjects 23 to 31 yr of age. The very low-frequency (VLF; 0.00-0.04 Hz) component of BPV tended to increase during HOI, whereas the low-frequency (LF; 0.04-0.15 Hz) component of BPV and the ratio of LF power to high-frequency (HF; 0.15-0.40 Hz) component (LF/HF ratio) of HRV decreased. The HF component of HRV increased in all the subjects during immersion up to the shoulder. Concomitantly, we found a decrease in heart rate and increases in stroke volume and cardiac output with no significant changes in BP and respiration rate during HOI. These results suggest that both vasomotor and cardiac sympathetic activities are suppressed and that the parasympathetic (vagal) activity is enhanced during HOI.

We herein report a 42-year-old man with advanced lung adenocarcinoma and nivolumab-associated dermatomyositis. Nivolumab, an anticancer drug that is classified as an immune checkpoint inhibitor, often induces immune-related adverse events (irAEs). However, there have so far been no reports regarding nivolumab-associated dermatomyositis. This patient was diagnosed with dermatomyositis due to the presence of proximal muscle weakness with abnormal electromyography and magnetic resonance imaging findings; skin lesions, such as heliotrope rash, shawl sign, and periungual erythema; and an elevated serum aldolase level after nivolumab administration. It is important to consider drug-associated dermatomyositis in the differential diagnosis of patients presenting with skin lesions and muscle weakness after nivolumab treatment.

Muscle sympathetic nerve activity (MSNA) is suppressed during thermoneutral head-out water immersion (HOI) in humans. In this study, the effects of ageing on the suppressive response of MSNA to HOI were determined. MSNA was recorded microneurographically from the tibial nerve in 16 healthy men, 10 of whom were aged 19-30 years (young group) and six aged 45-67 years (older group). MSNA was suppressed in all the subjects during HOI. The suppressive response was significantly less prominent in the older group than in the young group. A significant negative correlation between age and the suppressive response of MSNA induced by HOI (r = -0.53, P < 0.05) was found. We conclude that suppressive response of sympathetic nerve activity to HOI is reduced with age.