Salivary Gland Damage Research Articles

Identification of the protective mechanisms of Lactoferrin in the irradiated salivary gland

Radiotherapy is commonly used in patients with head and neck cancer, and usually results in irreversible salivary glands damage and hypofunction. It is therefore important to manage such irradiation to prevent damage to the salivary glands. A previous study showed that Lactoferrin (LF) has a radioprotective effect, but the mechanism was not determined in salivary glands. In the present study, we investigated the detailed radioprotective effect of LF using both ex vivo submandibular salivary gland organ culture and ICR male mice in vivo. We found that LF had effects on both cell proliferation and CyclinD1-mediated cell-cycle progression which were regulated via the ERK1/2 and AKT signal transduction pathways. In addition, LF affected acinar cell structure and function after irradiation. These findings suggest that LF may be a useful agent to prevent irradiation effects in salivary glands.

Elastin-PLGA hybrid electrospun nanofiber scaffolds for salivary epithelial cell self-organization and polarization.

Regenerating the salivary glands by mimicking the extracellular matrix (ECM) is a promising approach for long term treatment of salivary gland damage. Despite their topographic similarity to the ECM, electrospun fibers of synthetic polymers lack the biochemical complexity, elasticity and hydrophilicity of the ECM. Elastin is an ECM protein abundant in the salivary glands and responsible for tissue elasticity. Although it's widely used for tissue regeneration of other organs, little is known about its utility in regenerating the salivary tissue. This study describes the use of elastin to improve the elasticity, hydrophilicity and biochemical complexity of synthetic nanofibers and its potential in directing in vivo-like organization of epithelial salivary cells which helps the design of efficient salivary gland regeneration scaffolds.

Role of glial-cell-derived neurotrophic factor in salivary gland stem cell response to irradiation

Background and purposeRecently, stem cell therapy has been proposed to allow regeneration of radiation damaged salivary glands. It has been suggested that glial-cell-derived neurotrophic factor (GDNF) promotes survival of mice salivary gland stem cells (mSGSCs). The purpose of this study was to investigate the role of GDNF in the modulation of mSGSC response to irradiation and subsequent salivary gland regeneration. MethodsSalivary gland sphere derived cells of Gdnf hypermorphic (Gdnfwt/hyper) and wild type mice (Gdnfwt/wt) were irradiated (IR) with γ-rays at 0, 1, 2, 4 and 8Gy. mSGSC survival and stemness were assessed by calculating surviving fraction measured as post-IR sphere forming potential and population doublings. Flow cytometry was used to determine the CD24hi/CD29hi stem cell (SC) population. QPCR and immunofluorescence was used to detect GDNF expression. ResultsThe IR survival responses of mSGSCs were similar albeit resulted in larger spheres and an increased cell number in the Gdnfwt/hyper compared to Gdnfwt/wt group. Indeed, mSGSC of Gdnfwt/hyper mice showed high sphere forming efficiency upon replating. Interestingly, GDNF expression co-localized with receptor tyrosine kinase (RET) and was upregulated after IR in vitro and in vivo, but normalized in vivo after mSGSC transplantation. ConclusionGDNF does not protect mSGSCs against irradiation but seems to promote mSGSCs proliferation through the GDNF-RET signaling pathway. Post-transplantation stimulation of GDNF/RET pathway may enhance the regenerative potential of mSGSCs.

IgG4-related disease of the biliary tract and pancreas: clinical and experimental advances.

IgG4-related disease (IgG4-RD) is an immune-mediated disease of unknown cause. It predominantly affects the biliary tract [IgG4-associated cholangitis (IAC)] and pancreas [autoimmune pancreatitis (AIP)] of mostly elderly men. Accurate diagnostic tests are lacking. Patients benefit from predniso(lo)ne treatment. However, disease relapse is often seen. This review will address pathophysiological aspects and advances in diagnostic and therapeutic strategies. The role of IgG1 and IgG4 in the pathophysiology of IgG4-RD was studied in mice which showed more intense organ damage of pancreas and salivary glands when IgG1 rather than IgG4 of patients with IgG4-RD was injected. Coadministration of IgG1+IgG4 led to dampening of IgG1-mediated injury supporting the view that IgG4 exerts immune-dampening effects. IgG4+ B-cell receptor clones identified by next-generation sequencing and the IgG4/IgG RNA ratio in human blood assessed by quantitative PCR were able to accurately distinguish IAC/AIP from primary sclerosing cholangitis or pancreatobiliary malignancies. Long-term treatment with low-dose prednisolone was safe and reduced the number of flare-ups in patients with AIP. Early diagnosis by a novel accurate and easy-to-use qPCR test may prevent life-threatening complications, unnecessary interventions and fatal course because of misdiagnosis. Prednisolone treatment remains the standard of care in patients with IgG4-RD.

Protective/restorative Role of the Adipose Tissue-derived Mesenchymal Stem Cells on the Radioiodine-induced Salivary Gland Damage in Rats.

BackgroundTo analyze protective/regenerative effects of adipose tissue-derived mesenchymal stem cells (ADMSC) on 131I-Radioiodine (RAI)-induced salivary gland damage in rats.Materials and MethodsStudy population consisted of controls (n:6) and study groups (n:54): RAI (Group 1), ADMSC (Group 2), amifostine (Group 3), RAI+amifostine (Group 4), concomitant RAI+ADMSC (Group 5) and RAI+ADMSC after 48 h (Group 6). We used light microscopy (LM), transmission electron microscopy (TEM), and salivary gland scintigraphy (SGS), and analyzed data statistically.ResultsWe observed the homing of ADMSC in salivary glands at 1st month on LM. RAI exposure affected necrosis, periductal fibrosis, periductal sclerosis, vascular sclerosis and the total sum score were in a statistically significant manner (P < 0.05). Intragroup comparisons with LM at 1st and 6th months revealed statistically significant improvements in Group 6 (P < 0.05) but not in Groups 4 and 5. Intergroup comparisons of the total score showed that Groups 4 and 5 in 1st month and Group 6 in 6th month had the lowest values. TEM showed vacuolization, edema, and fibrosis at 1st month, and an improvement in damage in 6th month in Groups 5 and 6. SGSs revealed significant differences for the maximum secretion ratio (Smax) (P = 0.01) and the gland-to-background ratio at a maximum count (G/BGmax) (P = 0. 01) at 1st month, for G/BGmax (P = 0.01), Smax (P = 0.01) and the time to reach the maximum count ratio over the time to reach the minimum count (Tmax/Tmin) (P = 0.03) at 6th month. 1st and 6th month scans showed differences for Smax and G/BGmax (P = 0.04), but not for Tmax/Tmin (p > 0.05). We observed a significant deterioration in gland function in group 1, whereas, mild to moderate deteriorations were seen in protective treatment groups.ConclusionsOur results indicated that ADMSC might play a promising role as a protective/regenerative agent against RAI-induced salivary gland dysfunction.

Effect of selenium supplementation for protection of salivary glands from iodine-131 radiation damage in patients with differentiated thyroid cancer.

In the current study, we examined whether selenium supplementation during iodine-131 (131I) treatment had a radio-protective effect on salivary glands. Sixteen patients with differentiated thyroid cancer were prospectively enrolled in the study. Patients after total thyroidectomy, before 131I treatment, were divided into two groups; 8 patients in the selenium group and 8 patients in the control group. Patients in the selenium group received 300νg of selenium orally for 10 days, from 3 days before to 6 days after 131I treatment. The control group received a placebo over the same period. To assess salivary gland function, salivary gland scintigraphy was performed before and 6 months after 131I treatment. Serum amylase and whole blood selenium levels were measured before and 2 days and 6 months after 131I treatment. Using salivary gland scintigraphy, maximum uptake ratio (MUR), maximum secretion percentage (MSP), and ejection fraction (EF) of each salivary gland were calculated. Baseline clinical characteristics, baseline amylase and selenium levels, and parameters of baseline salivary gland scintigraphy were not significantly different between selenium and control groups (P>0.05). On a blood test performed 2 days after 131I treatment, the selenium group showed a significantly higher whole blood selenium level (P=0.008) and significantly lower serum amylase level (P=0.009) than the control group. On follow-up salivary gland scintigraphy, the control group showed significantly decreased, MUR of the bilateral parotid and left submandibular glands, MSP of the bilateral parotid and submandibular glands, and EF of the left submandibular glands (P<0.05), while the selenium group only had a significant decrease in MSP of the right submandibular gland and EF of the left submandibular gland (P<0.05). Selenium supplementation during 131I treatment was effective to reduce salivary glands damage by 131I radiation in patients with differentiated thyroid cancer.

Head and Neck Cancer Patients – Information for the General Dental Practitioner.

Salivary gland damage is the most common adverse effect associated with radiation therapy to the head and neck. A combination of hyposalivation and dietary changes, with a reduced emphasis on oral hygiene practices can contribute to a massive increase in a person’s caries risk status. This can be further complicated by limited mouth opening. To enable optimal dental care for head and neck cancer patients before, during and after radiation therapy, patients must be informed and educated about the potential risks of dental caries and the preventive strategies available. All patients should receive a pre-radiotherapy dental assessment by a Restorative Dentistry Consultant. This information will be delivered to the patient, often at an emotionally charged time, and can be lost amongst all the information related to other aspects of his/her cancer management. General Dental Practitioners (GDPs) are therefore in a pivotal position to reiterate this information post radiation therapy and ensure compliance with preventive strategies, with the overall aim to improve quality of life and avoid the need for future extractions and the resulting risk of osteoradionecrosis. Clinical relevance: This article highlights the GDP’s role in the shared management of head and neck cancer patients who have received radiotherapy as part of their cancer treatment. The critical issue of dental caries, one of the late effects of radiation-induced hyposalivation, will be focused upon. Other side-effects, such as trismus and osteoradionecrosis, will also be discussed. This article aims to supply GDPs with accurate information to provide to their patients with post radiation therapy, whilst highlighting what treatment is within their remit and when it may be appropriate to refer.

L1 Peptide–Conjugated Fibrin Hydrogels Promote Salivary Gland Regeneration

Hyposalivation contributes to dental caries, periodontitis, and microbial infections. Additionally, it impairs activities of daily living (e.g., speaking, chewing, and swallowing). Treatments for hyposalivation are currently limited to medications (e.g., the muscarinic receptor agonists pilocarpine and cevimeline) that induce saliva secretion from residual acinar cells and the use of saliva substitutes. However, given that these therapies provide only temporary relief, the development of alternative treatments to restore gland function is essential. Previous studies demonstrated that laminin 1 (L1) is critical for intact salivary cell cluster formation and organization. However, the full L1 sequence is not suitable for clinical applications, as each protein domain may contribute to unwanted effects, such as degradation, tumorigenesis, and immune responses that, when compounded, outweigh the potential benefits provided by their sum. Although the L1 peptides YIGSR and A99 linked to fibrin hydrogels (FHs) promote intact salivary epithelial formation in vitro, little is known about their role during salivary gland regeneration in vivo. Therefore, the goal of this study was to demonstrate whether L1 peptides conjugated to FHs promote tissue regeneration in a wound-healing model of mouse submandibular glands (mSMGs). Our results suggest that YIGSR-A99 peptides, chemically conjugated to FHs and applied to wounded mSMGs in vivo, formed new organized salivary tissue. In contrast, wounded mSMGs treated with FHs alone or in the absence of a scaffold showed disorganized collagen formation and poor tissue healing. Together these studies indicate that damaged salivary gland tissue can grow and differentiate when treated with FHs containing L1 peptides.

Organotypic Spheroid Culture to Mimic Radiation-Induced Salivary Hypofunction

Radiation treatment often leads to irreversible damage to normal salivary glands (SGs) because of their proximity to head and neck cancers. Optimization of the in vitro model of irradiation (IR)–induced SG damage is warranted to investigate pathophysiology and monitor treatment outcome. Here, we present an organotypic spheroid culture model to investigate the impact of IR on SGs and the mechanisms underlying IR-induced structural and functional changes. Human parotid epithelial cells were obtained from human parotid glands and plated on either plastic plates or Matrigel. A number of 3-dimensional (3D) spheroids were assembled on Matrigel. After IR at 10 and 20 Gy, morphologic changes in cells in 2D monolayers and 3D spheroids were observed. As the structural integrity of the 3D spheroids was destroyed by IR, the expression levels of salivary epithelial and structural proteins and genes decreased proportionally with radiation dosage. Furthermore, the spheroid culture allowed better measurement of functional alterations following IR relative to the monolayer culture, in which IR-inflicted spheroids exhibited a loss of acinar-specific cellular functions that enable Ca2+ influx or secretion of α-amylase in response to cholinergic or β-adrenergic agonists. p53-mediated apoptotic cell death was observed under both culture conditions, and its downstream signals increased, such as p53 upregulated modulator of apoptosis (PUMA), Bax, cytochrome c, caspase 9, and caspase 3. These results suggest that the organotypic spheroid culture could provide a useful alternative model for exploration of radiobiology and mode of action of new therapies for prevention of radiation-induced salivary hypofunction.

A Functional Scoring System Based on Salivary Gland Scintigraphy for Evaluating Salivary Gland Dysfunction Secondary to 131I therapy in Patients with Differentiated Thyroid Carcinoma.

Radioiodine therapy with 131I (131I therapy) after total or near-total thyroidectomy has been established as an effective treatment for Differentiated Thyroid Carcinoma (DTC), but can induce dry mouth symptoms by salivary gland damage and impair the patients' quality of life. To propose a functional scoring system based on Salivary Gland Scintigraphy (SGS) findings that evaluates development of salivary gland dysfunction secondary to 131I therapy in patients with DTC. This retrospective study evaluated the records of 279 DTC patients who underwent SGS after one or more round(s) of 131I therapy, using 370 MBqof 99mTc-pertechnetate. The SGS results were assessed using a novel functional scoring system in the Parotid Glands (PGs) and Submandibular Glands (SMGs) according to visual evaluations based on a three-point uptake score, Washout Rate (%WR) score after lemon-juice stimulation, and functional score. The scores were compared among pre treatment, low-dose (<10 GBq), and high-dose (>10 GBq) groups and among pre treatment, symptom-positive, and symptom-negative groups. Risk factors for dry mouth were analyzed by univariate and multivariate logistic regression analyses. Dry mouth symptoms developed in 15.4% of the DTC patients after 131I therapy. The three-point uptake, %WR, and functional scores in both the PG and SMG were statistically significant between low-dose and high-dose groups, and between symptom-positive and symptom-negative groups. The PG/SMG functional scores were independent risk factors for dry mouth (odds ratio, 0.03 and 0.0007 respectively). SGS-based PG and SMG functional scores were effective biomarkers to objectively evaluate salivary gland dysfunction, with the high strength of association with dry mouth symptoms.

Adipose-derived stromal cell in regenerative medicine: A review

The application of appropriate cell origin for utilizing in regenerative medicine is the major issue. Various kinds of stem cells have been used for the tissue engineering and regenerative medicine. Such as, several stromal cells have been employed as treat option for regenerative medicine. For example, human bone marrow-derived stromal cells and adipose-derived stromal cells (ADSCs) are used in cell-based therapy. Data relating to the stem cell therapy and processes associated with ADSC has developed remarkably in the past 10 years. As medical options, both the stromal vascular and ADSC suggests good opportunity as marvelous cell-based therapeutics. The some biological features are the main factors that impact the regenerative activity of ADSCs, including the modulation of the cellular immune system properties and secretion of bioactive proteins such as cytokines, chemokines and growth factors, as well as their intrinsic anti-ulcer and anti-inflammatory potential. A variety of diseases have been treated by ADSCs, and it is not surprising that there has been great interest in the possibility that ADSCs might be used as therapeutic strategy to improve a wider range of diseases. This is especially important when it is remembered that routine therapeutic methods are not completely effective in treat of diseases. Here, it was discuss about applications of ADSC to colitis, liver failure, diabetes mellitus, multiple sclerosis, orthopaedic disorders, hair loss, fertility problems, and salivary gland damage.

Chronic intoxication by methylmercury leads to oxidative damage and cell death in salivary glands of rats.

Methylmercury (MeHg) is one of the most toxic species of mercury, causing several systemic damages; however, its effect on the salivary glands has rarely been explored to date. This study was aimed at analyzing the mercury deposit, oxidative stress markers, and cell viability in parotid and submandibular rat salivary glands after chronic methylmercury intoxication. Herein, forty male Wistar rats (40 days old) were used in the experiment. The animals of the experimental group were intoxicated by intragastric gavage with MeHg at a dose of 0.04 mg per kg body weight per day for 35 days, whereas the control group received only corn oil, a diluent. After the period of intoxication, the glands were obtained for evaluation of total mercury deposit, cell viability, and the malondialdehyde (MDA) and the nitrite levels. Our results indicated mercury deposits in salivary glands, with a decrease in cell viability, higher levels of MDA in both glands of intoxicated animals, and a higher concentration of nitrite only in the submandibular gland of the mercury group. Thus, the intoxication by MeHg was able to generate deposits and oxidative stress in salivary glands that resulted in a decrease in cell viability in both types of glands.

Flaxseed oil: an emerging nutraceutical decimates cisplatin-induced submandibular salivary glands damage in rats

Objective The study aimed to investigate the capability of flaxseed oil (FXO) to alleviate the degenerative effect of chemotherapy with cisplatin (CP) on rats' submandibular salivary glands (SMGs). Materials and methods Rats were allocated equally into four groups: control, CP-treated, FXO-treated, and CP-FXO-treated groups. Rats of third and fourth groups were orally given a daily dose of FXO. After 10 days, rats in second and fourth groups were injected with a single dose of CP. After rat sacrifice, samples of SMGs were processed for histological, ultrastructural study beside immunohistochemical staining for Ki67 and vascular endothelial growth factor (VEGF) expressions. Analysis of variance was used to compare Ki67 and VEGF expressions between groups. Results The SMGs of CP group showed abnormal architecture when compared with control and FXO groups. CP group treated with FXO revealed architecture improvement in their SMGs. Immunohistochemical study revealed significant decrease in Ki67 and VEGF expressions in CP rats. However, CP group treated with FXO simulated control group in both Ki67 and VEGF expressions. Conclusion CP administration caused deleterious effects on rats' SMGs. However, dietary consumption of FXO was able to ameliorate CP effects. Hence, FXO intake is recommended simultaneously during chemotherapy with CP.

Encapsulation of primary salivary gland cells in enzymatically degradable poly(ethylene glycol) hydrogels promotes acinar cell characteristics.

Regenerative strategies to replace damaged salivary glands require the function and organization of acinar cells. Hydrogel-based approaches have shown promise to control cell function and phenotype. However, little is known about how specific parameters, such as the mechanism of hydrogel degradation (e.g., hydrolytic or enzymatic), influence the viability, proliferation, organization, and phenotype of salivary gland cells. In this work, it is shown that hydrogel-encapsulated primary salivary gland cell proliferation is dependent upon hydrogel degradation. Hydrogels crosslinked with enzymatically degradable peptides promoted the expression of critical acinar cell markers, which are typically downregulated in primary cultures. Furthermore, salivary gland cells encapsulated in enzymatically- but not hydrolytically-degradable hydrogels displayed highly organized and polarized salivary gland cell markers, which mimics characteristics found in native gland tissue. In sum, results indicate that salivary gland cells respond to cellularly remodeled hydrogels, resulting in self-assembly and organization akin to acini substructures of the salivary gland.

Alterations in ADAMTS12 gene expression in salivary glands of radioiodine-131-administered rats.

The aim of this study was to evaluate the alterations in ADAMTS12 expression after radioiodine-131 (RAI)-induced salivary gland damage. A total of 30 Wistar male albino rats (260±45 g, 6 months old) were studied for ADAMTS12 gene expression levels and histological changes in the parotid and submandibular salivary glands of rats after the administration of RAI. A series of healthy rats were used as controls. A 3 mCi (111 MBq) dose of RAI was administered to rats in group 1 (n=6), group 2 (n=6), group 3 (n=6), and group 4 (n=6) to induce salivary gland damage. Evaluations were performed at 24 h in controls and at 4, 24 h, 7, and 30 days after the administration of RAI. Quantitative and statistical analyses were carried out. In RAI-administered groups, the mean values of ADAMTS12 gene expression showed a distinct suppression over time for the parotid gland (groups 1-4: 0.38, 0.11, 0.10, and 0.18, respectively; P<0.05), but the values remained similar over time for the submandibular gland (groups 1-4: 1.59, 1.57, 1.03, and 1.00, respectively; P>0.05) compared with the controls. Histological evaluation indicated that RAI-administered groups had significant common nuclear coarsening and focal subnuclear vacuolization, but not in the control samples. Histological changes were more prominent in the parotid gland samples. Alterations in ADAMTS12 gene expression may play a role in RAI-induced salivary gland damage in rats.

T4/N2 classification nasopharyngeal carcinoma benefit from concurrent chemotherapy in the era of intensity-modulated radiotherapy.

Although the benefits of concurrent chemotherapy (CC) in the treatment of locally advanced nasopharyngeal carcinoma (NPC) had been proven in the era of two-dimensional radiotherapy, long-term efficacy and safety of using CC combined with intensity-modulated radiotherapy (IMRT) remain unclear. A retrospective analysis of 1,182 patients who underwent IMRT for clinical II-Iva NPC was performed. Propensity score matching algorithm was used to identify two matched cohorts with or without CC (264 patients per cohort). Median follow-up time was 45.6 and 43.6 months for the two cohorts. The estimated 5-year overall survival rate was 81.8% (95% CI 76.6-87.4) in patients treated with CC and 73.7% (95% CI 67.8-80.0) in those treated without CC, respectively (hazard ratio 0.64, 95% CI 0.44–0.93; p = 0.018). The benefit of CC was mainly observed in those patients with good performance status, male, age > 48 years, T4 and N2 classification. Grade 3/4 acute toxicities were more common in those patients administrated with CC. The grade and incidence of late salivary glands damage were also increased by CC (p = 0.003). These findings indicated that the addition of CC significantly improved treatment outcomes of NPC patients treated with IMRT, but accompanied increased toxicities. Tailored CC and optimizing schedule of IMRT and systemic therapy were needed, provided that distant metastasis was the predominant pattern of failure in patients treated with IMRT.

Risk Factors of 131I-Induced Salivary Gland Damage in Thyroid Cancer Patients.

Sialadenitis and xerostomia are major adverse effects of 131I therapy in thyroid cancer patients. The risk factors for these adverse effects, other than administered activity of 131I, have not been investigated. The aim of this study is to identify risk factors for 131I-induced salivary gland damage among follicular cell-derived thyroid cancer patients. We enrolled 216 thyroid cancer patients who visited The Ohio State University Wexner Medical Center between April 2013 and April 2014. Symptoms of xerostomia and sialadenitis were identified via questionnaire and medical record search. To validate the findings in a large cohort, we retrospectively searched for ICD-9/10 codes for sialadenitis, xerostomia, and autoimmune disease associated with Sjögren's syndrome (AID-SS) in our existing database (n = 1507). Demographic and clinical information was extracted from medical records. Multivariate analyses were performed to identify independent predictors for salivary gland damage. 131I treatment associated with higher incidence of xerostomia and sialadenitis. Patients with xerostomia had 46 mCi higher mean cumulative 131I activity and 21 mCi higher mean first-administered 131I activity than patients without xerostomia. Increased age associated with higher incidence of xerostomia, and females had a higher incidence of sialadenitis. Patients who experienced sialadenitis before 131I therapy had higher sialadenitis incidence after 131I therapy. 131I-treated patients diagnosed with AID-SS, whether before or after 131I treatment, had a higher incidence of xerostomia and sialadenitis among 131I-treated patients. Risk factors for 131I-induced salivary gland damage include administered 131I activity, age, gender, history of sialadenitis before 131I treatment, and AID-SS diagnosis.

Intraglandular Transplantation of Adipose-Derived Stem Cells for the Alleviation of Irradiation-Induced Parotid Gland Damage in Miniature Pigs

In a previous study, the authors verified the protective efficacy of adipose-derived stem cells (ADSCs) on the prevention of salivary gland (SG) damage induced by irradiation in mice. As a critical step before implementation in clinical practice, the present study investigated the protective effect of ADSCs in a miniature pig SG model, because miniature pigs share many characteristics with humans. Third-passage autologous ADSCs at a concentration of 4 × 106cells/mL were transplanted by intraglandular injection into parotid glands (PGs) immediately after local irradiation at a single dose of 20Gy. The injection process was repeated twice a week for 6 consecutive weeks. At 12weeks after irradiation, functional and histologic evaluations were performed by measuring salivary flow rate (SFR) and hematoxylin and eosin and periodic acid-Schiff staining. Immunohistochemical andtransmission electron microscopic examinations also were conducted to evaluate amylase (AMY) production, microvessel density (MVD), and microstructural changes. The irradiated PGs showed remarkable decreases in SFR, AMY production, and MVD. However, transplantation of ADSCs alleviated irradiated PG morphology and function by preserving more functional acinar cells and increasing SFR and AMY production. In addition, greater MVD was observed in the ADSC-treated group than in the irradiated group. These results indicated that intraglandular transplantation of autologous ADSCs is an effective method to protect PGs against damage from irradiation in miniature pigs, which might have clinic application in the future.

IMRT for head and neck cancer: reducing xerostomia and dysphagia.

Dysphagia and xerostomia are the main sequellae of chemoradiotherapy for head and neck cancer, and the main factors in reducing long-term patient quality of life. IMRT uses advanced technology to focus the high radiation doses on the targets and avoid irradiation of non-involved tissues. The decisions about sparing organs and tissues whose damage causes xerostomia and dysphagia depends on the evidence for dose–response relationships for the organs causing these sequellae. This paper discusses the evidence for the contribution of radiotherapy to xerostomia via damage of the major salivary glands (parotid and submandibular) and minor salivary glands within the oral cavity, and the contribution of radiotherapy-related effect on important swallowing structures causing dysphagia. Recommendations for dose limits to these organs, based on measurements of xerostomia and dysphagia following radiotherapy, are provided here.

Diffusion-weighted magnetic resonance imaging for evaluation of salivary gland function in head and neck cancer patients treated with intensity-modulated radiotherapy

Background and purposesPermanent xerostomia as a result of radiation-induced salivary gland damage remains a common side effect of radiotherapy (RT) of the head and neck. The purpose of this study was to evaluate the usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI) in assessing the post-RT salivary gland function in patients with head and neck cancer (HNC). Materials and methodsIn this prospective study, 20 HNC patients scheduled for bilateral neck chemoradiotherapy (CRT) with weekly cisplatin went through diffusion-weighted magnetic resonance imaging (DW-MRI) and salivary gland scintigraphy (SGS) prior to and at a mean of six months after completing the treatment. The changes in apparent diffusion coefficient (ADC) before and after treatment were compared with ejection fraction (EF) measured with SGS and the radiation dose absorbed by the salivary glands. ResultsAs a result of gustatory stimulation with ascorbic acid, the ADC showed a biphasic response with an initial increase and subsequent decrease. This pattern was seen both before and after RT. Post-RT ADC increased as a function of RT dose absorbed by the salivary glands. A moderate statistical correlation between pre- and post-RT ADCs at rest and EF measured with SGS was found. ConclusionsDW-MRI seems a promising tool for detection of physiological and functional changes in major salivary glands after RT.