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In previous papers (Randle & Smith, 1958a, b) evidence was presented that insulin, anoxia and substances such as salicylate or 2:4-dinitrophenol, which inhibit oxidative phosphorylation, increase the uptake of glucose and D-xylose by isolated rat diaphragm by accelerating the transfer of these sugars across the muscle-cell membrane. The conclusion was drawn that the transfer process for sugars in muscle is inhibited by a substance generated during oxidative phosphorylation and that insulin activates the transfer process by interfering with the action of this substance.

Background: Although there have been dramatic improvements in radiotherapy for head and neck squamous cell carcinoma (HNSCC), including robust intensity modulation and daily image guidance, these advances are not able to account for inherent structural and spatial changes that may occur during treatment. Many sources have reported volume reductions in the primary target, nodal volumes, and parotid glands over treatment, which may result in unintended dosimetric changes affecting the side effect profile and even efficacy of the treatment. Adaptive radiotherapy (ART) is an exciting treatment paradigm that has been developed to directly adjust for these changes. Main body: Adaptive radiotherapy may be divided into two categories: anatomy-adapted (A-ART) and responseadapted ART (R-ART). Anatomy-adapted ART is the process of re-planning patients based on structural and spatial changes occurring over treatment, with the intent of reducing overdosage of sensitive structures such as the parotids, improving dose homogeneity, and preserving coverage of the target. In contrast, response-adapted ART is the process of re-planning patients based on response to treatment, such that the target and/or dose changes as a function of interim imaging during treatment, with the intent of dose escalating persistent disease and/or deescalating surrounding normal tissue. The impact of R-ART on local control and toxicity outcomes is actively being investigated in several currently accruing trials. Conclusions: Anatomy-adapted ART is a promising modality to improve rates of xerostomia and coverage in individuals who experience significant volumetric changes during radiation, while R-ART is currently being studied to assess its utility in either dose escalation of radioresistant disease, or de-intensification of surrounding normal tissue following treatment response. In this paper, we will review the existing literature and recent advances regarding A-ART and R-ART.

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Neonatal ventricular myocytes that were incubated in a well-defined serum-free medium containing 50 mM KCl did not contract and maintained stable cell size, as assessed by the protein/DNA ratio. The present study utilized KCl-arrested cells to examine the effect of constant rates of synchronous contraction in normal [K+]o (4 mM) as a physiological stimulus for myocyte growth. Cell growth increased following the onset of contraction when measured over 3 days. The rate of protein synthesis was accelerated in parallel by contraction, but the rate of protein degradation remained similar to rates in noncontracting cells. The capacity for protein synthesis was estimated by total RNA content and was increased in contracting as compared with KCl-arrested cells. This increase was accompanied by faster rates of RNA synthesis as determined from the incorporation of [3H]uridine into RNA and the specific activity of the cellular UTP pool. The rate of RNA degradation was accelerated during contraction but the difference between the rates of RNA synthesis and degradation resulted in net RNA accumulation of 49% after 3 days. These data demonstrated that 1) contractile activity stimulated myocyte growth through an increased capacity for protein synthesis and 2) the increased capacity for protein synthesis involved acceleration of the rate of RNA synthesis. Since enhancement of protein synthetic capacity is a common feature of myocyte hypertrophy in vivo and in vitro, this model can be used to examine the regulation of ribosome synthesis during hypertrophic growth.