Multiglandular Parathyroid Carcinoma: Case Report and Review of The Literature

ObjectiveTo report the fifth case of multiglandular parathyroid carcinoma and highlight the necessity of bilateral neck exploration in some circumstances.MethodsWe report a case of simultaneous bilateral and multiglandular parathyroid carcinoma in a 48-yearold woman presenting with primary hyperparathyroidism. Ultrasonography revealed a 24-by 24-by 34-mm nodule on the right lobe of the thyroid and a 20-by 20-by 32-mm parathyroid gland inferior to the left thyroid lobe. Technetium Tc 99m sestamibi scan revealed bilateral increased uptake consistent with the parathyroid glands. She was treated with bilateral neck exploration and parathyroidectomy with en bloc resection of the adjacent thyroid lobe in the right lower gland and parathyroidectomy with resection of surrounding soft tissue in the left lower gland.ResultsThe presence of a thick fibrous capsule, invasion of surrounding tissues, trabecular and solid growth pattern without necrotic foci, and vascular invasion on pathology slides enabled the diagnosis of parathyroid carcinoma of both glands. Her calcium and parathyroid hormone levels were within normal limits during a follow-up period of 4 years.ConclusionSince surgical resection offers the only curative treatment and initial operation may be the determinant of survival, a high index of suspicion for carcinoma both clinically and intraoperatively is vital. We aim to reemphasize that bilateral neck exploration in select cases of parathyroid carcinoma should be considered if there is concrete evidence of a second tumor, since parathyroid carcinoma can coexist with hyperplasia, adenoma, or even carcinoma of other parathyroid glands. (Endocr Pract. 2011;17:e79-e83)     

The Rapalogue,CCI-779, Improves Salivary Gland Function following Radiation

The standard of care for head and neck cancer typically includes surgical resection of the tumor followed by targeted head and neck radiation. However depending on tumor location and stage, some cases may not require surgical resection while others may be treated with chemoradiation. Unfortunately, these radiation treatments cause chronic negative side effects for patients. These side effects are associated with damage to surrounding normal salivary gland tissue and include xerostomia, changes in taste and malnutrition. The underlying mechanisms of chronic radiation-induced salivary gland dysfunction are unknown, however, in rodent models persistently elevated proliferation is correlated with reduced stimulated salivary flow. The rapalogue, CCI-779, has been used in other cell systems to induce autophagy and reduce proliferation, therefore the aim of this study was to determine if CCI-779 could be utilized to ameliorate chronic radiation-induced salivary gland dysfunction. Four to six week old Atg5^f/f; Aqp5-Cre, Atg5^+/+; Aqp5-Cre and FVB mice were treated with targeted head and neck radiation. FVB mice were treated with CCI-779, chloroquine, or DMSO post-radiation. Stimulated salivary flow rates were determined and parotid and submandibular salivary gland tissues were collected for analyses. Mice with a defect in autophagy, via a conditional knockout of Atg5 in the salivary glands, display increased compensatory proliferation in the acinar cell compartment and hypertrophy at 24-72 hours following radiation. FVB mice treated with post-therapy CCI-779 have significant improvements in salivary gland physiology as determined by stimulated salivary flow rates, proliferation indices and amylase production and secretion. Consequently, post-radiation use of CCI-779 allows for improvement of salivary gland function and reestablishment of glandular homeostasis. As CCI-779 is already FDA approved for other uses, it could have a secondary use to alleviate the chronic side effects in head and neck cancer patients who have completed anti-tumor therapy.     

Hamartoma of the tongue: two case reports

Hamartoma designates an excessive focal overgrowth of mature normal cells and tissues in an organ or tissue composed of identical cellular elements. Two cases of hamartoma at the back of the tongue are reported. Histologically they comprised fibrous tissue, fat, salivary gland lobules, and smooth muscle. The literature is reviewed and discussed.     

Induction and differentiation of adipose-derived stem cells from human buccal fat pads into salivary gland cells

Atrophy or hypofunction of the salivary gland because of aging or disease leads to hyposalivation that affects patient quality of life by causing dry mouth, deterioration of mastication/deglutition, and poor oral hygiene status. Current therapy for atrophy or hypofunction of the salivary gland in clinical practice focuses on symptom relief using drugs and artificial saliva; therefore, there is still a need to develop new therapies. To investigate potential novel therapeutic targets, we induced the differentiation of salivary gland cells by co-culturing human adipose-derived stem cells isolated from buccal fat pads (hBFP-ASCs) with human salivary-gland-derived fibroblasts (hSG-fibros). We examined their potential for transplantation and tissue neogenesis. Following the culture of hBFP-ASCs and hSG-fibros, differentiated cells were transplanted into the submandibular glands of SCID mice, and their degree of differentiation in tissues was determined. We also examined their potential for functional tissue reconstitution using a three-dimensional (3D) culture system. Co-cultured cells expressed salivary-glandrelated markers and generated new tissues following transplantation in vivo. Moreover, cell reconstituted glandular structures in the 3D culture system. In conclusion, coculture of hSG-fibros with hBFP-ASCs led to successful differentiation into salivary gland cells that could be transplanted to generate new tissues.     

Aberrant Activation of the RANK Signaling Receptor Induces Murine Salivary Gland Tumors

Unlike cancers of related exocrine tissues such as the mammary and prostate gland, diagnosis and treatment of aggressive salivary gland malignancies have not markedly advanced in decades. Effective clinical management of malignant salivary gland cancers is undercut by our limited knowledge concerning the key molecular signals that underpin the etiopathogenesis of this rare and heterogeneous head and neck cancer. Without knowledge of the critical signals that drive salivary gland tumorigenesis, tumor vulnerabilities cannot be exploited that allow for targeted molecular therapies. This knowledge insufficiency is further exacerbated by a paucity of preclinical mouse models (as compared to other cancer fields) with which to both study salivary gland pathobiology and test novel intervention strategies. Using a mouse transgenic approach, we demonstrate that deregulation of the Receptor Activator of NFkB Ligand (RANKL)/RANK signaling axis results in rapid tumor development in all three major salivary glands. In line with its established role in other exocrine gland cancers (i.e., breast cancer), the RANKL/RANK signaling axis elicits an aggressive salivary gland tumor phenotype both at the histologic and molecular level. Despite the ability of this cytokine signaling axis to drive advanced stage disease within a short latency period, early blockade of RANKL/RANK signaling markedly attenuates the development of malignant salivary gland neoplasms. Together, our findings have uncovered a tumorigenic role for RANKL/RANK in the salivary gland and suggest that targeting this pathway may represent a novel therapeutic intervention approach in the prevention and/or treatment of this understudied head and neck cancer.     

Tissue distribution and characterization of predominant hemolymph carrier proteins from Dermacentor variabilis and Ornithodoros parkeri

The tissue distribution of the predominant hemolymph protein found throughout tick development was examined in the hard tick, Dermacentor variabilis, and in the soft tick, Ornithodoros parkeri. In D. variabilis, the predominant (purified) hemolymph protein was a lipoglycoheme-carrier protein (DvCP) with a molecular weight of 200 K. A protein with a similar mobility on native-PAGE was found in fat body, salivary gland, muscle and ovary from partially fed females which was most abundant in the plasma and salivary gland. DvCP from plasma, salivary gland and fat body of partially fed females consisted of two subunits on SDS-PAGE (98 and 92 K). In replete females, only salivary gland exhibited protein subunits equivalent to hemolymph CP. CP in salivary gland and fat body stained positive for lipids. The concentration of CP in tissues varied between partially fed and replete females, indicating a difference in the expression and/or sequestration of CP during adult development. The predominant hemolymph carrier protein from O. parkeri (OpCP) was purified to homogeneity for the first time and is presumed to have similar functions to CP from D. variabilis. Purified OpCP exhibited a molecular weight of 668 K by native-PAGE. Unlike CP from D. variabilis, OpCP was not detected in fat body or salivary gland tissues but occurred abundantly in coxal fluid. By SDS-PAGE, purified hemolymph OpCP consisted of two major subunits (114 and 93 K) and a less abundant protein with an apparent molecular weight of 48 K. Purified native OpCP was a lipoprotein like DvCP. A spectral analysis of purified OpCP failed to demonstrate the presence of heme like that found for CP from D. variabilis, purified by the same methods. However, plasma from O. parkeri contained heme with a λ_max of 410 nm.     

版纳微型猪近交系CD46基因克隆、序列及组织表达分析

根据猪NM_213888及EST序列,设计特异引物扩增BMI CD46基因,并进行克隆、测序和生物信息学分析。同时应用半定量RT-PCR技术对BMI 30个重要组织进行表达谱分析。获得了BMI CD46 1 092 bp的编码区序列（Gen Bank登录号：KJ513478）,编码363个氨基酸。分析表明,CD46蛋白质分子量（Mw）为39.60 k D,等电点（p I）为5.39,存在4个保守域和1个跨膜结构域,N端有信号肽序列;其N末端疏水,C末端亲水;亚细胞定位显示,该蛋白位于细胞周质的概率是56.7%。活性位点分析表明,BMI CD46蛋白有6类活性位点。系统进化分析表明,BMI与牛的亲缘关系最近。BMI 30种组织表达分析表明,CD46基因在十二指肠中高表达;在睾丸、胸腺、甲状腺、附睾、肺、淋巴结、空肠、回肠、结肠、小脑及舌下腺中中度表达;在颌下腺、肝、肾上腺、盲肠、直肠、食管、垂体及脑干中低表达;在心、脾、肾、肌肉、胰脏、胃、皮肤、大脑、下丘脑及脊髓中不表达。该结果为进一步研究基因功能奠定基础。     

Trace element levels in serum and gastric mucosa in patients with Helicobacter pylori positive and negative gastritis

BackgroundMost trace elements are inhibited by Helicobacter pylori-infection, and variations in specific element levels are linked to the development of stomach cancer. This is the first study to show the relationship between serum and tissue concentrations of twenty-five trace elements and H. pylori infection status. This study purposed to define serum and tissue trace element levels of 25 healthy individuals with Helicobacter pylori-positive gastritis and Helicobacter pylori-negative gastritis and to reveal their relationship with the disease.MethodsStudy groups consisted of sixty-two patients with Helicobacter pylori-positive, thirty-seven patients with Helicobacter pylori-negative, and thirty healthy individuals. Serum and tissue concentrations of twenty-five elements (aluminum, boron, arsenic, barium, calcium, beryllium, copper, cadmium, iron, chromium, mercury, lithium, potassium, magnesium, sodium, manganese, nickel, phosphorus, lead, scandium, strontium, selenium, tellurium, titanium, zinc) were defined by inductively coupled plasma optical emission spectrometry.ResultsExcept for copper, lithium, and strontium elements in serum samples, other trace elements differed significantly between the groups (p < 0.05). The serum chromium (p = 0.002), mercury (p = 0.001), boron (p < 0.001), and cadmium (p < 0.001) levels of H. pylori-negative gastritis and H. pylori-positive gastritis participants were significantly different, and their serum concentrations were less than 0.5 µ/l. Boron, barium, beryllium, chromium, lithium, phosphorus and strontium elements in tissue samples did not differ significantly between the groups (p > 0.05). Manganese, nickel, tellurium and titanium elements were not detected in tissue and serum samples. The mean concentrations of calcium, beryllium, chromium, iron, potassium, lithium, magnesium, scandium, and selenium were higher in the tissues of patients with H. pylori gastritis compared to healthy control tissues. Also, cadmium could not be detected in tissue samples. There was a significant difference between H. pylori-infected tissue and serum chromium levels (p = 0.001), with lower levels detected in tissue samples.ConclusionThis is the first study that we are knowledgeable of that reports the concentrations of twenty five elements in both serum and tissue samples, as well as the relationship between trace elements and Helicobacter pylori-infection status. Dietary adjustment is indicated as an adjunct to medical therapy to stabilize trace elements because Helicobacter pylori bacteria cause inflammation and impair element absorption in gastritis patients. We also think that this study will shed light on studies on the relationship between Helicobacter pylori-trace elements and serum-tissue/healthy serum-tissue trace element levels of patients with Helicobacter pylori gastritis.     

Parathyroid Hormone Level Changes Following Radioiodine Therapy for Thyroid Cancer: A Prospective Observational Study

ObjectiveOur objective was to analyze the effect of radioiodine (RAI) therapy on parathyroid hormone (PTH) secretion.MethodsA total of 137 patients were included and divided into 2 groups based on pretherapy PTH levels. The residual thyroid tissue volume was classified into 4 grades (0-3), and a value of 0 indicated that there was no apparent residual tissue. We analyzed the PTH level changes among different time points in each group and the factors that could predict the PTH level changes.ResultsIn 113 patients with normal parathyroid gland function, the PTH level at baseline, 1 day, 7 days, 1 month, 3 months, and 6 months after RAI therapy did not show any significant difference; in 24 patients with decreased parathyroid gland function, the level of PTH immediately decreased after the implementation of RAI therapy but gradually returned to a pre-RAI therapy level within 6 months. On the seventh day after therapy, the mean value of PTH in patients with a residual thyroid tissue volume of extent of 0/1 was 8.0 ± 2.3 pg/mL, which was significantly higher than that in patients with a residual thyroid tissue volume of extent of 2/3 (P = .011). Similar phenomena were observed 1 month, 3 months, and 6 months after therapy.ConclusionRAI therapy had a significant transient adverse effect on parathyroid gland function in patients with decreased PTH secretion pretherapy, and the extent was associated with the amount of residual thyroid tissue.     

Radioimmunoassay studies of intestinal calcium-binding protein in the pig. II. The distribution of intestinal CaBP in pig tissues.

Using a specific radioimmunoassay for porcine intestinal calcium-binding protein (CaBP), we have measured the concentration of CaBP in the various tissues and organs of normal pigs. Intestinal CaBP was present in highest concentration in the upper small intestine, with lower concentrations in the distal small intestine. Intestinal CaBP was also found, in lower concentrations, in kidney, liver, thyroid, pancreas, and blood. In all other tissues, including parathyroid, bone, skeletal muscle, and brain, CaBP immunoreactivity was undetectable or less than in blood. The elution profile of calcium-binding activity and immunoreactivity from gel filtration analysis of kidney and parathyroid extracts suggest that the calcium-binding protein in the parathyroid gland, and the major calcium-binding protein(s) in the kidney, are chemically and immunochemically different from intestinal CaBP.     

Diagnostic Fine-Needle Aspiration Biopsy of an Intrathyroidal Parathyroid Gland and Subsequent Eucalcemia in a Patient with Primary Hyperparathyroidism

ObjectiveTo present the clinical course of a patient with persistent primary hyperparathyroidism (PHPT) whose intrathyroidal parathyroid gland was diagnosed by ultrasound-guided fine-needle aspiration biopsy (FNAB).MethodsWe describe the clinical course and laboratory, radiographic, and microscopic findings of a patient with persistent PHPT due to an intrathyroidal cystic parathyroid gland and review the relevant literature.ResultsA 74-year-old man with PHPT (presenting serum calcium concentration, 16.2 mg/dL; intact parathyroid hormone [PTH] concentration, 341 pg/mL) had surgical excision of the right superior, right inferior, and left inferior parathyroid glands, but the left superior parathyroid gland remained unidentified. Microscopic examination revealed parathyroid hyperplasia. Technetium Tc 99m sestamibi single-photon emission computed tomography imaging showed uptake in 2 foci, 1 on each side of midline in the neck. Reoperation with attention to the left neck failed to locate another parathyroid gland. Neck ultrasonography demonstrated a complex nodule within the right lower lobe of the thyroid. Results from FNAB of the solid component were consistent with parathyroid cells, and cystic fluid PTH concentration was greater than 1800 pg/mL. Nine months later, neck ultrasonography showed a hypoechoic area located posterior to the inferior pole of the right thyroid. The patient remained eucalcemic 16 months postprocedure.ConclusionAutoinfarction of the parathyroid gland and aspiration of cystic fluid may explain resolution of hypercalcemia. Although PHPT due to functioning parathyroid cysts is rare, and PHPT due to cystic parathyroid hyperplasia has been described, this is the first case report of a patient with persistent PHPT due to a functional parathyroid cyst whose diagnosis by FNAB was followed by eucalcemia. (Endocr Pract. 2008;14:80-86)     

Trace Element Distribution in Selected Edible Tissues of Zebu (Bos indicus) Cattle Slaughtered at Jimma,SW Ethiopia

The amount of trace elements present in edible bovine tissues is of importance for both animal health and human nutrition. This study presents data on trace element concentrations in semitendinosus and cardiac muscles, livers and kidneys of 60 zebu (Bos indicus) bulls, sampled at Jimma, Ethiopia. From 28 of these bulls, blood samples were also obtained. Deficient levels of copper were found in plasma, livers, kidneys and semitendinosus muscles. Suboptimal selenium concentrations were found in plasma and semitendinosus muscles. Semitendinosus muscles contained high iron concentrations. Trace elements were mainly stored in the liver, except for iron and selenium. Cardiac muscles generally contained higher concentrations of trace elements than semitendinous muscles except for zinc. A strong association was found between liver and kidney concentrations of copper, iron, cobalt and molybdenum. Liver storage was well correlated with storage in semitendinosus muscle for selenium and with cardiac muscle for cobalt and selenium. Plasma concentrations of copper, selenium, cobalt were well related with their respective liver concentrations and for cobalt and selenium, also with cardiac muscle concentrations. The data suggest multiple trace element deficiencies in zebu cattle in South-West Ethiopia, with lowered tissue concentrations as a consequence. Based on the comparison of our data with other literature, trace element concentrations in selected edible tissues of Bos indicus seem quite similar to those in Bos taurus. However, tissue threshold values for deficiency in Bos taurus cattle need to be refined and their applicability for Bos indicus cattle needs to be evaluated.     

An Unusual Case of Primary Hyperparath Yroidism with Profoundly Elevated Parath Yroid Hormone Levels

ObjectiveTo report the case of a man who presented with profoundly elevated parathyroid hormone levels in the setting of hypercalcemia, a palpable neck mass, renal disease, and metabolic bone disease.MethodsWe describe the clinical, imaging, and laboratory findings of the patient, including results from genetic testing of the CDC73 gene (HRPT2), and review the relevant literature.ResultsA 28-year-old man with a history of childhood abdominal neuroblastoma treated with chemotherapy and field radiation therapy presented with a 2-week history of persistent left scapular pain and swelling. He had a freely mobile, 1-cm, homogeneous, nontender, firm nodule in the right anterior neck. Parathyroid hormone concentration at hospital admission was 1127 pg/mL. Single-photon emission computed tomography after intravenous administration of technetium Tc 99m–labeled sestamibi revealed an intense focus of abnormal radiotracer uptake on early and delayed images in the right anterior inferior neck. Computed tomography imaging of the chest and neck revealed a 1.9-cm, smooth, calcified nodule posterior to the right lobe of the thyroid gland and diffusely osteopenic bones with trabecular resorption and numerous scattered lucent regions consistent with brown tumors. On bilateral neck exploration, a right inferior parathyroid mass and the left superior parathyroid gland were excised. The remaining 2 parathyroid glands were identified intraoperatively and appeared normal. Genetic testing of the CDC73 gene did not detect germline mutations.ConclusionsThis case highlights the overlap between the clinical findings seen in primary hyperparathyroidism and parathyroid carcinoma. Enhanced understanding of the genetic and molecular bases of primary hyperparathyroidism and parathyroid carcinoma should aid in the diagnosis of these diseases and the care of affected patients. (Endocr Pract. 2008;14:892-897)     

X-chromosome methylation ratios as indicators of chromosomal activity: Evidence of intraindividual divergencies among tissues of different embryonal origin

To test whether the differentiation events that lead to the embryonal layers and their derived organs produce divergent X-chromosome activation ratios among the different tissues, the X-chromosome activation ratios in leucocytes and muscle (mesodermal origin), thyroid gland (endodermal origin) and medulla of the suprarenal glands (ectodermal origin) from ten deceased females were surveyed. Analysis of the degree of methylation of the polymorphic alleles recognized by the probes M27 and pSPT-PGK showed that the ratios for the medulla of the suprarenals correlated well with those of all other tissues except for leucocytes; the thyroid gland showed limited correlation with muscle, whereas leucocytes showed correlation only with muscle. The results of this preliminary study suggest that differentiation events result in considerable variation in the activation ratios in different tissues. As a consequence caution should be taken in extrapolating from the activation ratios observed in leucocytes or fibroblasts to tissues of endodermal or ectodermal origin.     

Immunohistochemical detection of secretoneurin, a novel neuropeptide endoproteolytically processed from secretogranin II, in normal human endocrine and neuronal tissues

Summary An antiserum raised against a synthetic peptide derived from the primary amino sequence of rat secretogranin II (chromogranin C) was used for immunological (quantitative radioimmunoassay analysis) and immunohistochemical studies of normal human endocrine and nervous tissues. This antibody recognized a novel and biologically active neuropeptide which was coined as secretoneurin. In endocrine tissues, secretoneurin was mainly co-localized with chromogranin A and B with some exceptions (e.g., parathyroid gland). Secretoneurin was demonstrated immunohistochemically in the adrenal medulla, thyroid C cells, TSH- and FSH/LH-produting cells of the anterior pituitary, A and B cells of pancreatic islets, in endocrine cells of the gastrointestinal tract and the bronchial mucosa, and the prostate. Immunoreactivity determined by radioimmunoassay analysis revealed high secretoneurin levels in the anterior and posterior pituitary and lower levels in pancreatic and thyroid tissue. A strong secretoneurin immunoreactivity was also found in ganglion cells of the submucdsal and myenteric plexus of the gastrointestinal tract, and in ganglionic cells of dorsal root ganglia, peripheral nerves, and ganglion cells of the adrenal medulla. Thus, secretoneurin may serve as a useful marker of gangliocytic/neuronal differentiation.     

Intraoperative Diagnostic Strategy to Distinguish Parathyroid Adenomas from Metastatic Thyroid Cancer

ObjectiveTo report the limitations of frozen section examination and the value of intraoperative tissue aspiration for parathyroid hormone assay to distinguish parathyroid adenomas from metastatic thyroid carcinoma.MethodsWe describe 2 patients with a biochemical diagnosis of primary hyperparathyroidism who underwent intraoperative frozen section analysis of suspected parathyroid tumors. Parathyroid gland aspiration for parathyroid hormone was also performed for confirmation.ResultsThe intraoperative frozen section examination of the suspected parathyroid tumors inaccurately identified the tumors as follicular carcinomas. The parathyroid gland aspirate, however, accurately substantiated the presence of parathyroid adenomas, rather than follicular cancers.ConclusionAspiration of a suspected parathyroid tumor for parathyroid hormone assay accurately determines whether a nodule is a parathyroid gland and facilitates intraoperative decision making, especially when frozen section diagnosis is misleading. (Endocr Pract. 2009; 15:454-457)     

Expression of neuronal growth inhibitory factor (metallothionein-III) in the salivary gland

Metallothioneins (MTs) are metal-binding proteins that have been regarded as intrinsic factors for protecting cells and tissues from metal toxicity and oxidants. Among the three major classes of MTs, MT-III is different from other MTs because it has neuronal inhibitory activity and is only expressed in the central nervous system. Recent studies, however, have confirmed that MT-III is also expressed in organs other than the brain. These findings not only indicate that MT-III has a much wider tissue distribution than was originally thought, but also suggest that it might have other unknown activities. In the present study, we examined the human salivary and thyroid glands and demonstrated that the MT-III gene is also expressed in the salivary but not in the thyroid gland. While salivary ducts showed intense immuno-reactivity with anti-MT-III, weak immunoreactivity was observed in acinar cells. This, together with the findings that some neuromodulators (i.e. nerve growth factor, etc.) exist in the salivary gland and that MT-III may participate in the transport in renal tubules, suggest that MT-III may have other functions than cytoprotection in the salivary gland.     

The effect of an extra-stimulus on successive inhibition following differentiations]

The influence of a foreign stimulus on the aftereffect of inhibitory stimuli was studied in experiments on dogs with salivary conditioned reflexes. The dynamics of temperature changes in the parotid salivary gland was used as an indicator since the action of a differentiation stimulus was accompanied by a drop in its temperature; each differentiation, whether rough, medium or fine--had its own limit of the gland's temperature drop during intensification of differentiation inhibition. It has been found that the dynamics of the gland temperature changes in the trace pauses and in response to a foreign stimulus depends on the modality of the stimulus, the duration of its action in the experiment, the typological properties of the animal's nervous system and the fineness of differentiation.     

Suppression of Radiation-Induced Salivary Gland Dysfunction by IGF-1

Background

Radiation is a primary or secondary therapeutic modality for treatment of head and neck cancer. A common side effect of irradiation to the neck and neck region is xerostomia caused by salivary gland dysfunction. Approximately 40,000 new cases of xerostomia result from radiation treatment in the United States each year. The ensuing salivary gland hypofunction results in significant morbidity and diminishes the effectiveness of anti-cancer therapies as well as the quality of life for these patients. Previous studies in a rat model have shown no correlation between induction of apoptosis in the salivary gland and either the immediate or chronic decrease in salivary function following γ-radiation treatment.

Methodology/Principal Finding

A significant level of apoptosis can be detected in the salivary glands of FVB mice following γ-radiation treatment of the head and neck and this apoptosis is suppressed in transgenic mice expressing an activated mutant of Akt (myr-Akt1). Importantly, this suppression of apoptosis in myr-Akt1 mice preserves salivary function, as measured by saliva output, three and thirty days after γ-radiation treatment. In order to translate these studies into a preclinal model we found that intravenous injection of IGF1 stimulated activation of endogenous Akt in the salivary glands in vivo. A single injection of IGF1 prior to exposure to γ-radiation diminishes salivary acinar cell apoptosis and completely preserves salivary gland function three and thirty days following irradiation.

Conclusions/Significance

These studies suggest that apoptosis of salivary acinar cells underlies salivary gland hypofunction occurring secondary to radiation of the head and neck region. Targeted delivery of IGF1 to the salivary gland of patients receiving head and neck irradiation may be useful in reducing or eliminating xerostomia and restoring quality of life to these patients.