Kirsten H. Limesand

Bio: Kirsten H. Limesand is an academic researcher from University of Arizona. The author has contributed to research in topics: Salivary gland & Saliva. The author has an hindex of 21, co-authored 49 publications receiving 1420 citations.

Clinical management of salivary gland hypofunction and xerostomia in head-and-neck cancer patients: successes and barriers

Abstract: The most significant long-term complication of radiotherapy in the head-and-neck region is hyposalivation and its related complaints, particularily xerostomia. This review addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy.

Sensitivity of Salivary Glands to Radiation: from Animal Models to Therapies

Abstract: Radiation therapy for head and neck cancer causes significant secondary side-effects in normal salivary glands, resulting in diminished quality of life for these individuals. Salivary glands are exquisitely sensitive to radiation and display acute and chronic responses to radiotherapy. This review will discuss clinical implications of radiosensitivity in normal salivary glands, compare animal models used to investigate radiation-induced salivary gland damage, address therapeutic advances, and project future directions in the field.

Radiation-induced salivary gland dysfunction results from p53-dependent apoptosis.

Abstract: Purpose Radiotherapy for head-and-neck cancer causes adverse secondary side effects in the salivary glands and results in diminished quality of life for the patient. A previous in vivo study in parotid salivary glands demonstrated that targeted head-and-neck irradiation resulted in marked increases in phosphorylated p53 (serine 18 ) and apoptosis, which was suppressed in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Methods and Materials Transgenic and knockout mouse models were exposed to irradiation, and p53-mediated transcription, apoptosis, and salivary gland dysfunction were analyzed. Results The proapoptotic p53 target genes PUMA and Bax were induced in parotid salivary glands of mice at early time points after therapeutic radiation. This dose-dependent induction requires expression of p53 because no radiation-induced expression of PUMA and Bax was observed in p53-/- mice. Radiation also induced apoptosis in the parotid gland in a dose-dependent manner, which was p53 dependent. Furthermore, expression of p53 was required for the acute and chronic loss of salivary function after irradiation. In contrast, apoptosis was not induced in p53-/- mice, and their salivary function was preserved after radiation exposure. Conclusions Apoptosis in the salivary glands after therapeutic head-and-neck irradiation is mediated by p53 and corresponds to salivary gland dysfunction in vivo .

Salivary Gland Hypofunction and Xerostomia in Head and Neck Radiation Patients.

Abstract: Background The most manifest long-term consequences of radiation therapy in the head and neck cancer patient are salivary gland hypofunction and a sensation of oral dryness (xerostomia). Methods This critical review addresses the consequences of radiation injury to salivary gland tissue, the clinical management of salivary gland hypofunction and xerostomia, and current and potential strategies to prevent or reduce radiation injury to salivary gland tissue or restore the function of radiation-injured salivary gland tissue. Results Salivary gland hypofunction and xerostomia have severe implications for oral functioning, maintenance of oral and general health, and quality of life. Significant progress has been made to spare salivary gland function chiefly due to advances in radiation techniques. Other strategies have also been developed, e.g., radioprotectors, identification and preservation/expansion of salivary stem cells by stimulation with cholinergic muscarinic agonists, and application of new lubricating or stimulatory agents, surgical transfer of submandibular glands, and acupuncture. Conclusion Many advances to manage salivary gland hypofunction and xerostomia induced by radiation therapy still only offer partial protection since they are often of short duration, lack the protective effects of saliva, or potentially have significant adverse effects. Intensity-modulated radiation therapy (IMRT), and its next step, proton therapy, have the greatest potential as a management strategy for permanently preserving salivary gland function in head and neck cancer patients.Presently, gene transfer to supplement fluid formation and stem cell transfer to increase the regenerative potential in radiation-damaged salivary glands are promising approaches for regaining function and/or regeneration of radiation-damaged salivary gland tissue.

Lifespan-extending caloric restriction or mTOR inhibition impair adaptive immunity of old mice by distinct mechanisms

Abstract: Aging of the world population and a concomitant increase in age-related diseases and disabilities mandates the search for strategies to increase healthspan, the length of time an individual lives healthy and productively. Due to the age-related decline of the immune system, infectious diseases remain among the top 5-10 causes of mortality and morbidity in the elderly, and improving immune function during aging remains an important aspect of healthspan extension. Calorie restriction (CR) and more recently rapamycin (rapa) feeding have both been used to extend lifespan in mice. Preciously few studies have actually investigated the impact of each of these interventions upon in vivo immune defense against relevant microbial challenge in old organisms. We tested how rapa and CR each impacted the immune system in adult and old mice. We report that each intervention differentially altered T-cell development in the thymus, peripheral T-cell maintenance, T-cell function and host survival after West Nile virus infection, inducing distinct but deleterious consequences to the aging immune system. We conclude that neither rapa feeding nor CR, in the current form/administration regimen, may be optimal strategies for extending healthy immune function and, with it, lifespan.

Modern Nutrition in Health and Disease

Abstract: This 11th edition of the book Modern Nutrition in Health and Disease, featuring the work of more than 190 expert authors and divided into five parts, fully explains and encapsulates the fundamentals of nutrition and its role in contemporary society, from mastering the basic science of nutrient metabolism and function to applying nutritional concepts to combat human disease. Part I comprehensively covers specific dietary components, including major dietary constituents, minerals, vitamins and other Other CABI sites 

Metformin—mode of action and clinical implications for diabetes and cancer

Abstract: Metformin has been the mainstay of therapy for diabetes mellitus for many years; however, the mechanistic aspects of metformin action remained ill-defined. Recent advances revealed that this drug, in addition to its glucose-lowering action, might be promising for specifically targeting metabolic differences between normal and abnormal metabolic signalling. The knowledge gained from dissecting the principal mechanisms by which metformin works can help us to develop novel treatments. The centre of metformin's mechanism of action is the alteration of the energy metabolism of the cell. Metformin exerts its prevailing, glucose-lowering effect by inhibiting hepatic gluconeogenesis and opposing the action of glucagon. The inhibition of mitochondrial complex I results in defective cAMP and protein kinase A signalling in response to glucagon. Stimulation of 5'-AMP-activated protein kinase, although dispensable for the glucose-lowering effect of metformin, confers insulin sensitivity, mainly by modulating lipid metabolism. Metformin might influence tumourigenesis, both indirectly, through the systemic reduction of insulin levels, and directly, via the induction of energetic stress; however, these effects require further investigation. Here, we discuss the updated understanding of the antigluconeogenic action of metformin in the liver and the implications of the discoveries of metformin targets for the treatment of diabetes mellitus and cancer.

The twilight of immunity: emerging concepts in aging of the immune system

Abstract: Immunosenescence is a series of age-related changes that affect the immune system and, with time, lead to increased vulnerability to infectious diseases. This Review addresses recent developments in the understanding of age-related changes that affect key components of immunity, including the effect of aging on cells of the (mostly adaptive) immune system, on soluble molecules that guide the maintenance and function of the immune system and on lymphoid organs that coordinate both the maintenance of lymphocytes and the initiation of immune responses. I further address the effect of the metagenome and exposome as key modifiers of immune-system aging and discuss a conceptual framework in which age-related changes in immunity might also affect the basic rules by which the immune system operates.

Nuclei Segmentation with Recurrent Residual Convolutional Neural Networks based U-Net (R2U-Net)

Abstract: Bio-medical image segmentation is one of the promising sectors where nuclei segmentation from high-resolution histopathological images enables extraction of very high-quality features for nuclear morphometrics and other analysis metrics in the field of digital pathology. The traditional methods including Otsu thresholding and watershed methods do not work properly in different challenging cases. However, Deep Learning (DL) based approaches are showing tremendous success in different modalities of bio-medical imaging including computation pathology. Recently, the Recurrent Residual U-Net (R2U-Net) has been proposed, which has shown state-of-the-art (SOTA) performance in different modalities (retinal blood vessel, skin cancer, and lung segmentation) in medical image segmentation. However, in this implementation, the R2U-Net is applied to nuclei segmentation for the first time on a publicly available dataset that was collected from the Data Science Bowl Grand Challenge in 2018. The R2U-Net shows around 92.15% segmentation accuracy in terms of the Dice Coefficient (DC) during the testing phase. In addition, the qualitative results show accurate segmentation, which clearly demonstrates the robustness of the R2U-Net model for the nuclei segmentation task.