Estradiol receptor profile and estrogen responsiveness in laryngeal cancer and clinical outcomes.

There is growing evidence that laryngeal cancers are responsive to sex hormones, specifically 17ß-estradiol (E2), despite controversy regarding the presence and characterization of E2 receptors (ER). Determination of sex hormone responsiveness impacts the prognosis of laryngeal cancer patients and the treatment modalities implemented by their clinicians. Discovery of membrane-associated steroid hormone receptors and rapid membrane signaling opened the possibility that cancers previously labeled 'non-hormone dependent' and 'ER negative' might in fact be susceptible to the effects of E2 via these membrane receptors. ERα66 and ERß, the classical nuclear receptors, are present in the membranes of different cancer cells via a mechanism referred to as trafficking. Novel splice variants of these traditional receptors, a key example being ERα36, have also been found in the caveolae of cancer cells. Previous work demonstrated that ERα36 has a role in the tumorigenesis of laryngeal cancer, enhancing both proliferation and the anti-apoptotic effect of E2 against chemotherapeutics. The present study showed that expression of different membrane ERs in laryngeal cancer is not uniform, which may result in differential and even antagonistic responses to E2. E2 had protective or deleterious effects in different cancer cell lines, stimulating proliferation and conferring anti-apoptotic potential to the cancer cells according to their receptor profile. These findings stress the importance of establishing the molecular and clinical characterization of the specific laryngeal tumor in order to tailor treatment accordingly, thus optimizing care while reducing adverse effects for individual patients.

Decellularized Muscle Supports New Muscle Fibers and Improves Function Following Volumetric Injury.

Current strategies to treat volumetric muscle loss use primarily pedicle or free muscle transfers, but these grafts fail to adequately regenerate functional tissue. Decellularized soft tissue grafts possess physical and chemical cues to promote muscle regeneration, suggesting their potential for use in large muscle defects. In this study, we developed a decellularized muscle matrix (DMM) graft using rat gastrocnemius. Anisotropy and chemical components of the extracellular matrix were retained, including laminin, fibronectin, and collagen. We compared the ability of DMM, autologous muscle grafts (clinical standard), and type I collagen plugs (negative control) to support muscle regeneration. DMM supported regeneration over a 56-day period in 1 × 1 cm and 1.5 × 1 cm gastrocnemius defects in rats. Muscle function tests demonstrated improved muscle recovery in rats with DMM grafts when compared to collagen. Histological sections were assessed using morphometrics and immunostaining. DMM supported muscle regeneration with less fibrosis and more de novo neuromuscular receptors than either autograft or collagen. Overall, our results indicate that DMM may be used as a muscle replacement graft based on its ability to improve muscle function recovery, promote muscle regeneration, and support new neuromuscular junctions.

Rapid steroid hormone actions via membrane receptors.

Steroid hormones regulate a wide variety of physiological and developmental functions. Traditional steroid hormone signaling acts through nuclear and cytosolic receptors, altering gene transcription and subsequently regulating cellular activity. This is particularly important in hormonally-responsive cancers, where therapies that target classical steroid hormone receptors have become clinical staples in the treatment and management of disease. Much progress has been made in the last decade in detecting novel receptors and elucidating their mechanisms, particularly their rapid signaling effects and subsequent impact on tumorigenesis. Many of these receptors are membrane-bound and lack DNA-binding sites, functionally separating them from their classical cytosolic receptor counterparts. Membrane-bound receptors have been implicated in a number of pathways that disrupt the cell cycle and impact tumorigenesis. Among these are pathways that involve phospholipase D, phospholipase C, and phosphoinositide-3 kinase. The crosstalk between these pathways has been shown to affect apoptosis and proliferation in cardiac cells, osteoblasts, and chondrocytes as well as cancer cells. This review focuses on rapid signaling by 17ß-estradiol and 1α,25-dihydroxy vitamin D3 to examine the integrated actions of classical and rapid steroid signaling pathways both in contrast to each other and in concert with other rapid signaling pathways. This new approach lends insight into rapid signaling by steroid hormones and its potential for use in targeted drug therapies that maximize the benefits of traditional steroid hormone-directed therapies while mitigating their less desirable effects.