RESUMO
Sjögren's syndrome (SS) is an autoimmune disorder characterized by oral dryness that is primarily attributed to tumor necrosis factor alpha (TNF-α)-mediated reduction in saliva production. In traditional Chinese medicine, goji berries are recognized for their hydrating effect and are considered suitable to address oral dryness associated with Yin deficiency. In the present study, we used goji berry juice (GBJ) to investigate the potential preventive effect of goji berries on oral dryness caused by SS. Pretreatment of human salivary gland cells with GBJ effectively prevented the decrease in aquaporin-5 (AQP-5) mRNA and protein levels induced by TNF-α. GBJ also inhibited histone H4 deacetylation and suppressed the generation of intracellular reactive oxygen species (ROS). Furthermore, GBJ pretreatment reserved mitochondrial membrane potential and suppressed the upregulation of Bax and caspase-3, indicating that GBJ exerted an antiapoptotic effect. These findings suggest that GBJ provides protection against TNF-α in human salivary gland cells and prevents the reduction of AQP-5 expression on the cell membrane. Altogether, these results highlight the potential role of GBJ in preventing oral dryness caused by SS.
Assuntos
Lycium , Síndrome de Sjogren , Xerostomia , Humanos , Fator de Necrose Tumoral alfa/metabolismo , Lycium/metabolismo , Glândulas Salivares/metabolismo , Glândulas Salivares/patologia , Xerostomia/induzido quimicamente , Xerostomia/prevenção & controle , Xerostomia/complicações , Síndrome de Sjogren/complicações , Síndrome de Sjogren/metabolismo , Síndrome de Sjogren/patologia , Aquaporina 5/genéticaRESUMO
BACKGROUND AND PURPOSE: Parotid gland lymphoma (PGL) is a rare and challenging diagnosis. Different lymphomas can develop in the parotid gland, with the most common being the mucosa-associated lymphoid tissue (MALT) lymphoma, which originates directly from the glandular parenchyma. Other histologic subtypes arise from both intraglandular and extraglandular parotid lymph nodes. A consensus on diagnosis and treatment of PGL is still lacking, and published data is scarce and heterogeneous. METHODS: We performed a systematic review of the literature, including studies published after 2001, when the WHO classification of lymphoid tumours was introduced. RESULTS: Twenty retrospective studies were included in the analyses, eight of which focused exclusively on MALT lymphomas. Final analysis included 612 cases of PGL, with a 1.68:1 F/M ratio. MALT lymphoma was the most common histology, followed by follicular and diffuse large B-cell lymphoma. Most cases were low stages (IE/IIE acc. Ann Arbour, 76.5%) and only 10% of patients presented with symptoms, most commonly pain (4.8%) and B symptoms (2.2%). A high prevalence of associated autoimmune diseases was found, particularly Sjögren's syndrome, that affected up to 70% of patients with MALT lymphoma. In most cases diagnosis was achieved through parotidectomy (57.5%), or open biopsy (31.2%). Treatment strategies were either surgical, non-surgical or a combination of modalities. Surgery as a single-modality treatment was reported in about 20% of patients, supposing it might be a valuable option for selected patients. CONCLUSIONS: Our review showed that the diagnosis and treatment of PGLs is far from being standardized and needs further, more homogeneous reports to reach consensus.
Assuntos
Linfoma de Zona Marginal Tipo Células B , Neoplasias Parotídeas , Síndrome de Sjogren , Humanos , Glândula Parótida/patologia , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/terapia , Linfoma de Zona Marginal Tipo Células B/complicações , Estudos Retrospectivos , Glândulas Salivares/patologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Neoplasias Parotídeas/diagnóstico , Neoplasias Parotídeas/cirurgiaRESUMO
Adjuvant radioactive iodine (RAI) is administered to thyroid cancer patients following thyroidectomy for remnant tissue ablation and metastatic disease management. Patients are prepared with thyroid hormone withdrawal (THW) or recombinant human thyroid stimulating hormone (rhTSH). Long-term salivary gland dysfunction (LT-SGD) is a common, dosage-dependent, RAI adverse effect. Although rhTSH preparation seems to reduce LT-SGD, this effect could be due to lower RAI activity generally used in rhTSH-prepared patients. Therefore, this meta-analysis investigated the effect of preparation type on LT-SGD development. Literature search (PubMed, Medline, EmBase, Cochrane, Web of Science, LILACS, Google Scholar) was performed four times (January-November 2022) and studies reporting LT-SGD incidence ≥1 year after RAI in patients prepared with rhTSH/THW were identified. The LT-SGD risk ratio (RR) was estimated with various models considered for sensitivity analysis (fixed-effect, random-effects, study-quality adjusted, publication-bias adjusted, individual-patient-data meta-analysis adjusted for RAI). Subgroup analysis according to RAI activity (<3.7/≥3.7 GBq) also was performed. Literature search resulted in five studies (321 rhTSH, 632 THW patients). The pooled RRs according to various models were 0.65 (95% confidence interval -95CI, 0.49-0.86; fixed-effect); 0.62 (95CI, 0.38-1.02; random-effects); 0.72 (95CI, 0.54-0.96; quality adjusted); 0.76 (95CI, 0.58-0.99; publication-bias adjusted); 0.0.80 (95CI, 0.55-1.14; individual-patient-data meta-analysis). The pooled RRs stratified for RAI activity were 0.26 (95CI, 0.05-1.30) for <3.7 GBq; 0.75 (95CI, 0.57-0.98) for ≥3.7 GBq. The number of patients needed to be prepared with rhTSH to prevent one case of LT-SGD ranged between seven and thirty-seven. There is moderate-quality scientific evidence that rhTSH preparation may consistently protect salivary gland function.
Assuntos
Neoplasias da Glândula Tireoide , Tirotropina Alfa , Humanos , Neoplasias da Glândula Tireoide/patologia , Radioisótopos do Iodo , Tireotropina , Estudos Retrospectivos , Tireoidectomia , Glândulas Salivares/patologiaRESUMO
BACKGROUND: In recent years the number of studies on special tumor entities in the head and neck region has increased. During the 2021 meetings of the American Society of Clinical Oncology (ASMO) and the European Society for Medical Oncology (ESMO), several studies were presented which predict changes in clinical treatment algorithms for nasopharyngeal carcinoma, salivary gland, and thyroid cancer. OBJECTIVE: Future treatment alterations in specific head and neck tumor entities were evaluated after screening clinical studies presented at the 2021 ASCO and ESMO meetings. MATERIALS AND METHODS: A systematic analysis of the phase II and III clinical trials for nasopharyngeal carcinoma, salivary gland, and thyroid cancer treatment presented at ASCO and ESMO 2021 was performed. Taking into account current treatment standards, the results are structured in terms of their potential clinical significance. RESULTS AND CONCLUSION: In curative treatment of advanced nasopharyngeal carcinoma, adjuvant therapy with capecitabine after primary chemoradiation should be discussed as a new standard. In the palliative treatment of nasopharyngeal carcinoma, an increasing role of immunotherapy can be predicted. Recurrent or metastatic salivary gland cancer can often be treated very effectively with targeted substances if molecular target lesions are present. Immunotherapies currently play a subordinate role; they only seem to be effective in a few patients with salivary gland cancer, who cannot currently be reliably identified using predictive markers. Patients with radioiodine-refractory differentiated thyroid cancer benefit from treatment with the multi-tyrosine kinase inhibitor cabozantinib after failure of vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) therapy.
Assuntos
Neoplasias Nasofaríngeas , Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo/uso terapêutico , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Glândulas Salivares/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/terapia , Fator A de Crescimento do Endotélio Vascular/uso terapêuticoRESUMO
SCOPE: This study aims to evaluate the therapeutic efficacy and mechanisms of Lycium barbarum polysaccharide (LBP) in primary Sjögren's syndrome (pSS). METHODS AND RESULTS: Non-obese diabetic mice (the pSS model) are randomly divided into four groups: Low dose LBP (LBP.L, 5 mg kg-1 d-1 ), high dose LBP (10 mg kg-1 d-1 ), low dose interleukin (IL)-2 (25 000 IU/d), and control (saline water). Drugs were treated for 12 weeks. LBP.L significantly reduces the salivary gland inflammation compared with the control group (histological score p LBP.L vs Control = 0.019; foci number: p LBP.L vs Control = 0.038). LBP.L also remarkably reduces the effector follicular helper T (Tfh) cells and the CD4+ IL-17A+ helper T (Th17) cells in both spleen and cervical lymph node (cLN) cells. Additionally, the ratios of regulatory T cell (Treg)/Tfh cells and Treg/Th17 cells are substantially increased in mice treated with LBP.L in both spleen and cLNs. LBP also inhibits Th17 and Tfh cells and markedly increases the Treg/Tfh ratio in human peripheral blood mononuclear cells. CONCLUSION: LBP.L inhibits the progression of pSS in mice, associated with modulation of T cell differentiation.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Glândulas Salivares/efeitos dos fármacos , Síndrome de Sjogren/tratamento farmacológico , Animais , Autoanticorpos/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Centro Germinativo/efeitos dos fármacos , Centro Germinativo/patologia , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Células T de Memória/efeitos dos fármacos , Camundongos Endogâmicos NOD , Glândulas Salivares/patologia , Glândulas Salivares/fisiopatologia , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia , Baço/citologia , Baço/efeitos dos fármacos , Linfócitos T ReguladoresRESUMO
Despite wide application of sodium nitrite (SN) as food additive, it exhibits considerable side effects on various body organs at high dose or chronic exposure. The aim of this study was to test whether Glycyrrhizic acid (GA) could ameliorate SN-induced toxicity in lung and submandibular salivary gland (SMG). A sample size of 30 adult male albino rats was randomly allocated into 3 groups. Group 1 served as control group. Rats were treated orally with 80 mg/kg of SN in group 2 or SN preceded by (15 mg/kg) GA in group 3. Lung & SMG tissues were used for oxidative stress assessment, examination of histopathological changes, fibrosis (MTC, TGF-ß and α-SMA) and inflammation (TNF-α, IL-1ß and CD-68). Concurrent administration of GA ameliorated pulmonary and salivary SN-induced toxicity via restoring the antioxidant defense mechanisms with reduction of MDA levels. GA reduced the key regulators of fibrosis TGF-ß and α-SMA and collagen deposition. In addition to reduction of inflammatory cytokine (TNF-α, IL-1ß) and macrophages recruitments, GA amended both pulmonary and salivary morphological changes. The present study proposed GA as a promising natural herb with antioxidant, anti-inflammatory and antifibrotic effects against pulmonary and salivary SN-induced toxicity.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Ácido Glicirrízico/uso terapêutico , Pulmão/efeitos dos fármacos , Glândulas Salivares/efeitos dos fármacos , Nitrito de Sódio/toxicidade , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Fibrose , Glutationa/metabolismo , Ácido Glicirrízico/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Glândulas Salivares/metabolismo , Glândulas Salivares/patologiaRESUMO
Previous studies based on animal models demonstrated that N-acetylcysteine (NAC) prevents oxidative stress and improves salivary gland function when the NAC supplementation starts simultaneously with insulin resistance (IR) induction. This study is the first to evaluate the effect of a 4-week NAC supply on the antioxidant barrier and oxidative stress in Wistar rats after six weeks of high-fat diet (HFD) intake. Redox biomarkers were evaluated in the parotid (PG) and submandibular (SMG) salivary glands and stimulated whole saliva (SWS), as well as in the plasma and serum. We demonstrated that the activity of salivary peroxidase and superoxide dismutase and total antioxidant capacity were significantly higher in PG, SMG, and SWS of IR rats treated with NAC. It appears that in PG and SMG of rats fed an HFD, N-acetylcysteine supplementation abolishes oxidative modifications to proteins (evidenced by decreased content of advanced oxidation protein products (AOPP) and advanced glycation end products (AGE)). Simultaneously, it does not reverse oxidative modifications of lipids (as seen in increased concentration of 8-isoprostanes and 4-hydroxynonenal vs. the control), although it reduces the peroxidation of salivary lipids in relation to the group fed a high-fat diet alone. NAC administration increased protein levels in PG and SMG but did not affect saliva secretion, which was significantly lower compared to the controls. To sum up, the inclusion of NAC supplementation after six weeks of HFD feeding was effective in improving the general and salivary gland antioxidant status. Nevertheless, NAC did not eliminate salivary oxidative stress and only partially prevented salivary gland dysfunction.
Assuntos
Acetilcisteína/farmacologia , Sequestradores de Radicais Livres/farmacologia , Hiperglicemia , Resistência à Insulina , Estresse Oxidativo/efeitos dos fármacos , Glândulas Salivares , Animais , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Masculino , Ratos , Ratos Wistar , Glândulas Salivares/metabolismo , Glândulas Salivares/patologiaRESUMO
This is the first study to assess the effect of N-acetylcysteine (NAC) on the mitochondrial respiratory system, as well as free radical production, glutathione metabolism, nitrosative stress, and apoptosis in the salivary gland mitochondria of rats with high-fat diet (HFD)-induced insulin resistance (IR). The study was conducted on male Wistar rats divided into four groups of 10 animals each: C (control, rats fed a standard diet containing 10.3% fat), C + NAC (rats fed a standard diet, receiving NAC intragastrically), HFD (rats fed a high-fat diet containing 59.8% fat), and HFD + NAC (rats fed HFD diet, receiving NAC intragastrically). We confirmed that 8 weeks of HFD induces systemic IR as well as disturbances in mitochondrial complexes of the parotid and submandibular glands of rats. NAC supplementation leads to a significant increase in the activity of complex I, II + III and cytochrome c oxidase (COX), and also reduces the ADP/ATP ratio compared to HFD rats. Furthermore, NAC reduces the hydrogen peroxide production/activity of pro-oxidant enzymes, increases the pool of mitochondrial glutathione, and prevents cytokine formation, apoptosis, and nitrosative damage to the mitochondria in both aforementioned salivary glands of HFD rats. To sum up, NAC supplementation enhances energy metabolism in the salivary glands of IR rats, and prevents inflammation, apoptosis, and nitrosative stress.
Assuntos
Acetilcisteína/farmacologia , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Glutationa/metabolismo , Resistência à Insulina , Mitocôndrias/metabolismo , Estresse Nitrosativo/efeitos dos fármacos , Glândulas Salivares/metabolismo , Animais , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Metabolismo Energético/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Masculino , Ratos Wistar , Glândulas Salivares/patologiaRESUMO
BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) provides a standardized reporting system for salivary gland fine-needle aspiration (SGFNA). We review the clinical utility of the MSRSGC at a tertiary care cancer center by assessing the rates of malignancy (ROM) among different categories. METHODS: A retrospective search was performed to retrieve all SGFNA cases performed at our institution between 1/1/07 and 12/31/18. The initial primary diagnoses were recorded and cases were then assigned to appropriate MSRSGC categories. ROM was then calculated for all categories. RESULTS: A total of 976 cases were identified, and 373 with follow-up. The ROM was 19.7% (192/976) for all-comers and 51.3% (192/374) among cases with follow-up. Using MSRSGC, SGFNA showed a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 65.6%, 87.4%, 100%, and 72.6%, respectively. ROM for MSRSGC categories I, II, III, IVa, IVb, V, and VI were 20.7%, 30.0%, 45.8%, 3.3%, 50.7%, 100%, and 100%, respectively. Utilizing MSRSGC resulted in a nondiagnostic rate of 14.4%. The nondiagnostic rate was lower when the procedure was performed by pathologists vs nonpathologists (12.9% vs 15.8%) but was comparable when rapid on site evaluation (ROSE) was performed (12.9% vs 11.6%). CONCLUSION: In our patient population, MSRSGC resulted in a perfect PPV and moderate NPV. Utilizing MSRSGC results in a higher nondiagnostic rate due to the inclusion of cases with benign elements or cyst contents only in this category. Performing ROSE is more important in attaining an adequate sample than the specialty of the person performing SGFNA.
Assuntos
Algoritmos , Institutos de Câncer , Neoplasias das Glândulas Salivares , Glândulas Salivares , Adulto , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/metabolismo , Glândulas Salivares/patologiaRESUMO
Treatment of differentiated thyroid cancer often involves administration of radioactive iodine (I-131) for remnant ablation or adjuvant therapy. However, there is morbidity associated with I-131 therapy, which can result in both acute and chronic complications. Currently, there are no approved radioprotectors that can be used in conjunction with I-131 to reduce complications in thyroid cancer therapy. It is well known that the damaging effects of ionizing radiation are mediated, in part, by the formation of reactive oxygen species (ROS). A potent scavenger of ROS, Mn(III)meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP), has radioprotective and anti-tumor effects in various cancer models including head and neck, prostate, and brain tumors exposed to external beam radiation therapy. Female C57BL/6 mice were administered I-131 orally at doses of 0.0085-0.01 mCi/g (3.145 × 105 to 3.7 × 105 Bq) of body weight with or without MnTnBuOE-2-PyP. We measured acute external inflammation, blood cell counts, and collected thyroid tissue and salivary glands for histological examination. We found oral administration of I-131 caused an acute decrease in platelets and white blood cells, caused facial swelling, and loss of thyroid and salivary tissues. However, when MnTnBuOE-2-PyP was given during and after I-131 administration, blood cell counts remained in the normal range, less facial inflammation was observed, and the salivary glands were protected from radiation-induced killing. These data indicate that MnTnBuOE-2-PyP may be a potent radioprotector of salivary glands in thyroid cancer patients receiving I-131 therapy.
Assuntos
Radioisótopos do Iodo/efeitos adversos , Metaloporfirinas/uso terapêutico , Protetores contra Radiação/uso terapêutico , Compostos Radiofarmacêuticos/efeitos adversos , Neoplasias da Glândula Tireoide/radioterapia , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Metaloporfirinas/farmacologia , Camundongos Endogâmicos C57BL , Protetores contra Radiação/farmacologia , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/patologia , Glândulas Salivares/efeitos da radiação , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/patologia , Glândula Tireoide/efeitos da radiação , Neoplasias da Glândula Tireoide/patologiaRESUMO
Interstitial nephritis and immune complex-mediated glomerulonephritis are the two common renal manifestations of primary Sjögren's syndrome (SS). Here, we discuss three cases of primary SS where presenting manifestation was distal renal tubular acidosis. The possibility of an underlying autoimmune disorder should be considered in a patient presenting with distal tubular acidosis or recurrent hypokalemic periodic paralysis as treatment of primary disease improves the outcome of illness.
Assuntos
Acidose Tubular Renal/imunologia , Paralisia Periódica Hipopotassêmica/imunologia , Síndrome de Sjogren/imunologia , Acidose Tubular Renal/diagnóstico , Acidose Tubular Renal/tratamento farmacológico , Adulto , Biópsia , Suplementos Nutricionais , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Paralisia Periódica Hipopotassêmica/diagnóstico , Paralisia Periódica Hipopotassêmica/tratamento farmacológico , Túbulos Renais Distais/imunologia , Túbulos Renais Distais/patologia , Potássio/uso terapêutico , Recidiva , Glândulas Salivares/imunologia , Glândulas Salivares/patologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/tratamento farmacológico , Esteroides/uso terapêutico , Resultado do TratamentoRESUMO
Ephedrae Herba (EH) has been used in Asian traditional herbal medicine to cure bronchial asthma, cold, flu, chills, fever, headache, nasal congestion, and cough. In this study, we evaluated the subchronic toxicity of an Ephedrae Herba aqueous extract (EHAE) in male and female F344 rats. The EHAE was administered orally daily at doses of 0, 125, 250, 500, and 1000â¯mg/kgâ¯bw/day for 13 weeks. Toxicological assessment was performed to determine mortality, clinical signs, and changes in body weight, food consumption, ophthalmological, urinary, hematological, and serum biochemical parameters, macroscopic and microscopic evaluations, and organ weights. We found that oral administration of EHAE to F344 rats for 13 weeks resulted in histopathological changes in the kidneys and salivary glands. In the kidneys, increased incidence and severity of tubular basophilia were observed in females administered 1000â¯mg/kgâ¯bw/day of the extract. In the salivary glands, acinar cell hypertrophy was observed in males administered 500â¯mg/kgâ¯bw/day and in both sexes administered 1000â¯mg/kgâ¯bw/day of the extract. All test article-treated groups of males and females administered ≥250â¯mg/kgâ¯bw/day showed increased absolute and relative salivary gland weights. Therefore, the NOAEL (No Observed Adverse Effect Level) was determined as 125â¯mg/kgâ¯bw/day for both sexes of rats under the present experimental conditions.
Assuntos
Ephedra , Extratos Vegetais/toxicidade , Animais , Feminino , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Nível de Efeito Adverso não Observado , Ratos Endogâmicos F344 , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/patologia , Testes de Toxicidade SubcrônicaRESUMO
Iodine is an important micronutrient required for nutrition. Excess iodine has adverse effects on thyroid, but there is not enough information regarding its effect on salivary glands. In addition to food and iodized salt, skin disinfectants and maternal nutritional supplements contain iodide, so its intake could be excessive during pregnancy, lactation, and infancy. The aim of this work was to evaluate the effect of excess iodide ingestion on salivary glands during mating, gestation, lactation, and postweaning period in mouse. During assay, mice were allocated into groups: control and treatment groups (received distilled water with NaI 1 mg/mL). Water intake, glandular weight, and histology were analyzed. Treatment groups showed an increase in glandular weight and a significantly (p < 0.05) higher water intake than control groups. Lymphocyte infiltration was observed in animals of treatment groups, while there was no infiltration in glandular sections of control groups. Results demonstrated that a negative relationship could exist between iodide excess and salivary glands. This work is novel evidence that high levels of iodide intake could induce mononuclear infiltration in salivary glands. These results should be considered, especially in pregnant/lactating women, to whom a higher iodine intake is usually recommended.
Assuntos
Iodetos/farmacologia , Glândulas Salivares/efeitos dos fármacos , Animais , Ingestão de Líquidos/efeitos dos fármacos , Feminino , Iodetos/administração & dosagem , Masculino , Camundongos , Tamanho do Órgão , Gravidez , Glândulas Salivares/patologiaAssuntos
Carcinoma Mucoepidermoide/diagnóstico , Imunoglobulina G/análise , Neoplasias/diagnóstico , Neoplasias Parotídeas/diagnóstico , Esclerose/diagnóstico , Adulto , Carcinoma Mucoepidermoide/patologia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias/patologia , Glândula Parótida/patologia , Neoplasias Parotídeas/patologia , Glândulas Salivares/patologia , Esclerose/patologiaRESUMO
To examine genes expressed specifically in labial salivary glands (LSGs) of patients with Sjögren's syndrome (SS) in comparison with those of patients with immunoglobulin (Ig)G4-related disease (IgG4-RD), and to identify the genes involved in the pathogenesis of SS. Gene expression in LSGs of SS patients, IgG4-RD patients and healthy controls (HC) was analysed by cDNA microarray. Quantitative polymerase chain reaction (qPCR) was used to validate the up-regulation of differentially expressed genes (DEGs) in SS. Protein production of the validated gene in LSGs was examined by immunofluorescence (IF) assay. The association of molecular functions of the gene with the pathological conditions in SS was examined using peripheral blood lymphocytes. Among 1320 DEGs up-regulated in SS, qPCR confirmed the up-regulation of NR4A2 in LSGs of SS compared with IgG4-RD. IF staining showed higher production of NR4A2 in nuclei of CD4+ T cells and interleukin (IL)-17-producing cells in LSGs of SS, compared with IgG4-RD. Over-expression of NR4A2 mRNA was observed in peripheral CD4+ T cells of SS patients, compared with HC. Nuclear NR4A2 expression in T helper type 17 (Th17)-polarized CD4+ T cells determined by cellular IF was significantly higher in SS than in HC. Importazole, an inhibitor of importin-ß, inhibited nuclear transport of NR4A2 and Th17 polarization along with IL-21 expression in naive CD4+ T cells under Th17-polarizing conditions, but did not alter retinoic acid receptor-related orphan receptor C (RORC) expression. NR4A2 seems to promote Th17 polarization via increased expression and intranuclear localization in CD4+ T cells of SS patients, which could play a critical role in the pathogenesis of SS.
Assuntos
Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Quinazolinas/uso terapêutico , Glândulas Salivares/fisiologia , Síndrome de Sjogren/metabolismo , Células Th17/imunologia , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Adulto , Idoso , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , DNA Complementar/análise , Feminino , Perfilação da Expressão Gênica , Humanos , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/metabolismo , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Interleucinas/metabolismo , Pessoa de Meia-Idade , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Quinazolinas/farmacologia , Glândulas Salivares/patologia , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/genética , Células Th17/efeitos dos fármacos , Análise Serial de Tecidos/métodos , beta Carioferinas/antagonistas & inibidoresRESUMO
ACC is one of the most malignant tumors in salivary gland, and of poor prognosis. A critical role in ACC development and progression is played by EGFR family members including EGFR. EGCG, a low molecular weight polyphenol contained in green tea, has broad anticancer properties, but whether EGCG regulates activity of ACC is unknown. In the present study, the effects of EGCG were investigated in vitro with particular attention to the pathway of EGFR/Erk and mitochondria apoptosis in SACC-83 cell lines. The results of MTS assay and flow cytometry demonstrated that EGCG (20-80 µM) could inhibit proliferation and promote apoptosis of SACC-83 cells. Furthermore, by Western blotting with antibodies specific for EGFR, Erk 1/2 (p-Erk 1/2), Mek (p-Mek), Bcl-2, and Bax, it was demonstrated that EGCG could reduce the expression of EGFR, inhibit phosphorylation of Erk 1/2 and Mek, downregulate Bcl-2, and upregulate Bax. In addition, it was also shown that EGCG could inhibit mRNA expression of P90 RSK by RT-PCR. In conclusion, the results suggest that EGCG might be a potential therapeutic or adjuvant strategy for the treatment of patients with ACC, by inhibiting proliferation and inducing the apoptosis of the tumor cells.
Assuntos
Apoptose , Carcinoma Adenoide Cístico/patologia , Catequina/análogos & derivados , Mitocôndrias , Transdução de Sinais , Carcinoma Adenoide Cístico/tratamento farmacológico , Catequina/farmacologia , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Humanos , Glândulas Salivares/patologiaRESUMO
Objective. The aim of this study was to investigate effects of aromatherapy in decreasing salivary gland damage for patients undergoing radioactive iodine (RAI) therapy with differentiated thyroid cancer (DTC). Materials and Methods. The subjects were 71 patients with DTC. They were divided into aromatherapy group (group A, n = 35) and a control group (group B, n = 36). We blended 1.0 mL of lemon and 0.5 mL of ginger essential oils. The patients in the inhalation aromatherapy group inhaled this blend oil and those in the control group inhaled distilled water as placebo for 10 min during admission. We statistically compared salivary gland function before and after treatment between groups A and B. Results. In comparison with group B, the rate of change of the accumulation rate was significantly higher in the parotid glands and submandibular glands of group A (P < 0.05). In comparison with group B, a significant increase in rate of secretion change before and after treatment was noted in the bilateral parotid glands in group A (P < 0.05). Conclusion. Because an amelioration of salivary gland function was observed in the present study, our results suggest the efficacy of aromatherapy in the prevention of treatment-related salivary gland disorder. This trial is registered with UMIN Clinical Trial Registry: UMIN000013968.
Assuntos
Aromaterapia , Óleos Voláteis/administração & dosagem , Glândulas Salivares/efeitos dos fármacos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cintilografia , Glândulas Salivares/diagnóstico por imagem , Glândulas Salivares/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapiaRESUMO
PURPOSE: To test the effects of a novel Mn porphyrin oxidative stress modifier, Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin (MnBuOE), for its radioprotective and radiosensitizing properties in normal tissue versus tumor, respectively. METHODS AND MATERIALS: Murine oral mucosa and salivary glands were treated with a range of radiation doses with or without MnBuOE to establish the dose-effect curves for mucositis and xerostomia. Radiation injury was quantified by intravital near-infrared imaging of cathepsin activity, assessment of salivation, and histologic analysis. To evaluate effects of MnBuOE on the tumor radiation response, we administered the drug as an adjuvant to fractionated radiation of FaDu xenografts. Again, a range of radiation therapy (RT) doses was administered to establish the radiation dose-effect curve. The 50% tumor control dose values with or without MnBuOE and dose-modifying factor were determined. RESULTS: MnBuOE protected normal tissue by reducing RT-mediated mucositis, xerostomia, and fibrosis. The dose-modifying factor for protection against xerostomia was 0.77. In contrast, MnBuOE increased tumor local control rates compared with controls. The dose-modifying factor, based on the ratio of 50% tumor control dose values, was 1.3. Immunohistochemistry showed that MnBuOE-treated tumors exhibited a significant influx of M1 tumor-associated macrophages, which provides mechanistic insight into its radiosensitizing effects in tumors. CONCLUSIONS: MnBuOE widens the therapeutic margin by decreasing the dose of radiation required to control tumor, while increasing normal tissue resistance to RT-mediated injury. This is the first study to quantitatively demonstrate the magnitude of a single drug's ability to radioprotect normal tissue while radiosensitizing tumor.
Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Metaloporfirinas/uso terapêutico , Mucosa Bucal/efeitos da radiação , Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/uso terapêutico , Radiossensibilizantes/uso terapêutico , Glândulas Salivares/efeitos da radiação , Animais , Relação Dose-Resposta à Radiação , Avaliação Pré-Clínica de Medicamentos/métodos , Fibrose/etiologia , Fibrose/prevenção & controle , Metaloporfirinas/farmacocinética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Órgãos em Risco/patologia , Órgãos em Risco/efeitos da radiação , Doses de Radiação , Protetores contra Radiação/farmacocinética , Radiossensibilizantes/farmacocinética , Distribuição Aleatória , Glândulas Salivares/patologia , Estomatite/etiologia , Estomatite/prevenção & controle , Xerostomia/etiologia , Xerostomia/prevenção & controleRESUMO
BACKGROUND: Protein-tyrosine sulfation is a post-translational modification of an unknown number of secreted and membrane proteins mediated by two known Golgi tyrosylprotein sulfotransferases (TPST-1 and TPST-2). We reported that Tpst2-/- mice have mild-moderate primary hypothyroidism, whereas Tpst1-/- mice are euthyroid. While using magnetic resonance imaging (MRI) to look at the thyroid gland we noticed that the salivary glands in Tpst2-/- mice appeared smaller than in wild type mice. This prompted a detailed analysis to compare salivary gland structure and function in wild type, Tpst1-/-, and Tpst2 -/- mice. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative MRI imaging documented that salivary glands in Tpst2-/- females were (≈) 30% smaller than wild type or Tpst1-/- mice and that the granular convoluted tubules in Tpst2-/- submandibular glands were less prominent and were almost completely devoid of exocrine secretory granules compared to glands from wild type or Tpst1-/- mice. In addition, pilocarpine-induced salivary flow and salivary α-amylase activity in Tpst2-/- mice of both sexes was substantially lower than in wild type and Tpst1-/- mice. Anti-sulfotyrosine Western blots of salivary gland extracts and saliva showed no differences between wild type, Tpst1-/-, and Tpst2-/- mice, suggesting that the salivary gland hypofunction is due to factor(s) extrinsic to the salivary glands. Finally, we found that all indicators of hypothyroidism (serum T4, body weight) and salivary gland hypofunction (salivary flow, salivary α-amylase activity, histological changes) were restored to normal or near normal by thyroid hormone supplementation. CONCLUSIONS/SIGNIFICANCE: Our findings conclusively demonstrate that low body weight and salivary gland hypofunction in Tpst2-/- mice is due solely to primary hypothyroidism.
Assuntos
Hipotireoidismo/metabolismo , Glândulas Salivares/metabolismo , Sulfotransferases/metabolismo , Animais , Western Blotting , Peso Corporal/efeitos dos fármacos , Peso Corporal/genética , Peso Corporal/fisiologia , Suplementos Nutricionais , Feminino , Expressão Gênica , Hipotireoidismo/sangue , Hipotireoidismo/genética , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Glândulas Salivares/patologia , Glândulas Salivares/fisiopatologia , alfa-Amilases Salivares/metabolismo , Glândula Submandibular/metabolismo , Glândula Submandibular/patologia , Glândula Submandibular/fisiopatologia , Sulfotransferases/genética , Tireoide (USP)/administração & dosagem , Tireoide (USP)/farmacologia , Tiroxina/sangueRESUMO
Sjögren's syndrome is a chronic illness manifested characteristically by immune injury to the salivary and lacrimal glands, resulting in dry mouth/eyes. Anti-Ro [Sjögren's syndrome antigen A (SSA)] and anti-La [Sjögren's syndrome antigen B (SSB)] autoantibodies are found frequently in Sjögren's subjects as well as in individuals who will go on to develop the disease. Immunization of BALB/c mice with Ro60 peptides results in epitope spreading with anti-Ro and anti-La along with lymphocyte infiltration of salivary glands similar to human Sjögren's. In addition, these animals have poor salivary function/low saliva volume. In this study, we examined whether Ro-peptide immunization produces a Sjögren's-like illness in other strains of mice. BALB/c, DBA-2, PL/J, SJL/J and C57BL/6 mice were immunized with Ro60 peptide-274. Sera from these mice were studied by immunoblot and enzyme-linked immunosorbent assay for autoantibodies. Timed salivary flow was determined after pharmacological stimulation, and salivary glands were examined pathologically. We found that SJL/J mice had no immune response to the peptide from Ro60, while C57BL/6 mice produced antibodies that bound the peptide but had no epitope spreading. PL/J mice had epitope spreading to other structures of Ro60 as well as to La, but like C57BL/6 and SJL/J had no salivary gland lymphocytic infiltration and no decrement of salivary function. DBA-2 and BALB/c mice had infiltration but only BALB/c had decreased salivary function. The immunological processes leading to a Sjögren's-like illness after Ro-peptide immunization were interrupted in a stepwise fashion in these differing mice strains. These data suggest that this is a model of preclinical disease with genetic control for epitope spreading, lymphocytic infiltration and glandular dysfunction.