We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjogren's syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.
Adult ; Autoantibodies/blood ; C-Reactive Protein/analysis ; Demography ; Female ; Germinal Center/*pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Receptors, Complement 3d/metabolism ; Retrospective Studies ; Salivary Glands, Minor/*pathology ; Sjogren's Syndrome/immunology/metabolism/*pathology

We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjogren's syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.
Adult ; Autoantibodies/blood ; C-Reactive Protein/analysis ; Demography ; Female ; Germinal Center/*pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Receptors, Complement 3d/metabolism ; Retrospective Studies ; Salivary Glands, Minor/*pathology ; Sjogren's Syndrome/immunology/metabolism/*pathology

OBJECTIVETo investigate the genetic association pattern between single-nucleotide polymorphisms (SNP) of key genes in T regulatory cells signaling pathways and the efficacy of allergic rhinitis (AR) specific immune therapy(SIT).

METHODSA population of 102 AR patients(Beijing Tongren hospital, from January to Decemeber 2012) caused by simple dust mite received standardized specific immune therapy, who lived in Beijing region was recruited. In immunotherapy before and after 1 years of treatment, the study objects were scored by nasal symptoms score, nasal signs score and total score of daily life distress three indicators to assess the efficacy. A total of 43 reprehensive marker SNP which were in FOXP3, IL-2, TGF-βand EBI3 gene regions and the upstream and downstream 1 000 kb were selected according to the Beijing people database from Hapmap website. The individual genotyping was performed by MassARRAY platform.Plink software was used for statistic analysis.

RESULTSSubgroup analysis for the efficacy evaluation of three indicators displayed that IL-2_rs77468365, FOXP3(rs2280883, rs2232365 and rs3761548) were associated with the improvement of sneezing in nasal symptoms. IL-2_rs77468365, FOXP3(rs2280883, rs2232365 and rs3761548) were associated with the improvement of runny nose in nasal symptoms. TGF-β(rs747857, rs6508975, rs2241715, rs12462166, rs12983775, rs1800470 and rs2317130)and FOXP3(rs2280883, rs2232365 and rs3761548)were associated with the improvement of nasal obstruction in nasal symptoms. FOXP3(rs2280883, rs2232365 and rs3761548)were associated with the improvement of nasal itching in nasal symptoms. IL-2_rs77468365 and FOXP3(rs2280883, rs2232365 and rs3761548) were associated with the overall improvement in nasal symptoms. EBI3_rs670188 and FOXP3(rs2280883, rs2232365, rs3761549, rs3761548 and rs3761547) were associated with the improvement of inferior turbinate mucosa swelling in nasal signs. IL-2_rs77468365, EBI3_rs393581, TGF-β(rs11466359 and rs11466345), FOXP3(rs2280883, rs17847095, rs2232365 and rs3761548)were associated with the improvement of inferior turbinate mucosa color in nasal signs. EBI3(rs393581, rs4740 and rs353702), FOXP3(rs2280883, rs2232365 and rs3761548)were associated with the improvement of water discharge in nasal signs. IL-2_rs77468365, EBI3(rs393581, rs4740 and rs353702), FOXP3( rs2280883, rs2232365 and rs3761548)were associated with the overall improvement in nasal signs. TGF-β(rs12461895, rs2241717 and rs7258445), FOXP3(rs2280883, rs2232365, rs3761549, rs3761548 and rs3761547)were associated with the improvement of life puzzle.

CONCLUSIONThe genetic polymorphism (SNPs) of four important functional candidate genes( FOXP3, IL-2, TGF-βand EBI3) in T regulatory cells signaling pathways were detected in significant correlation with the efficacy of allergic rhinitis specific immune therapy.

Beijing ; Forkhead Transcription Factors ; genetics ; Genotype ; Humans ; Immunotherapy ; Interleukin-2 ; genetics ; Interleukins ; genetics ; Minor Histocompatibility Antigens ; Polymorphism, Single Nucleotide ; Rhinitis, Allergic ; genetics ; therapy ; Signal Transduction ; T-Lymphocytes, Regulatory ; cytology ; Transforming Growth Factor beta1 ; genetics ; Turbinates ; pathology

Our previous studies indicate that phosphatidylinositol 4-kinase IIα can promote the growth of multi-malignant tumors via HER-2/PI3K and MAPK pathways. However, the molecular mechanisms of this pathway and its potential for clinical application remain unknown. In this study, we found that PI4KIIα could be an ideal combinatorial target for EGFR treatment via regulating EGFR degradation. Results showed that PI4KIIα knockdown reduced EGFR protein level, and the expression of PI4KIIα shows a strong correlation with EGFR in human breast cancer tissues (r = 0.77, P < 0.01). PI4KIIα knockdown greatly prolonged the effects and decreased the effective dosage of AG-1478, a specific inhibitor of EGFR. In addition, it significantly enhanced AG1478-induced inhibition of tumor cell survival and strengthened the effect of the EGFR-targeting anti-cancer drug Iressa in xenograft tumor models. Mechanistically, we found that PI4KIIα suppression increased EGFR ligand-independent degradation. Quantitative proteomic analysis by stable isotope labeling with amino acids in cell culture (SILAC) and LC-MS/MS suggested that HSP90 mediated the effect of PI4KIIα on EGFR. Furthermore, we found that combined inhibition of PI4KIIα and EGFR suppressed both PI3K/AKT and MAPK/ERK pathways, and resulted in downregulation of multiple oncogenes like PRDX2, FASN, MTA2, ultimately leading to suppression of tumor growth. Therefore, we conclude that combined inhibition of PI4KIIα and EGFR exerts a multiple anti-tumor effect. Dual inhibition of EGFR at protein and activity level via combinatorial blocking of PI4KIIα presents a novel strategy to combat EGFR-dependent tumors.
Animals ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Survival ; drug effects ; ErbB Receptors ; antagonists & inhibitors ; metabolism ; Female ; HSP90 Heat-Shock Proteins ; metabolism ; Humans ; MCF-7 Cells ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Minor Histocompatibility Antigens ; Mitogen-Activated Protein Kinases ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphotransferases (Alcohol Group Acceptor) ; antagonists & inhibitors ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Quinazolines ; pharmacology ; Transplantation, Heterologous ; Tyrphostins ; pharmacology

Pleomorphic adenoma is the most common tumour of the salivary gland. While the majority arises from the parotid gland, only a small percentage arises from the minor salivary glands. The cheek, however, is a rarely affected site with respect to pleomorphic adenomas of the minor salivary glands. Herein, we report a case of pleomorphic adenoma of the cheek, which presented with intraoral swelling, and conclude that complete surgical excision can be a curative treatment for this benign tumour.
Adenoma, Pleomorphic ; pathology ; Adult ; Biopsy, Fine-Needle ; Cheek ; Diagnosis, Differential ; Humans ; Male ; Salivary Gland Neoplasms ; pathology ; Salivary Glands, Minor ; pathology

OBJECTIVETo investigate the prognosis of adenoid cystic carcinoma (ACC) in minor salivary glands and its influencing factors.

METHODSClinical data of 52 patients with ACC in minor salivary glands were reviewed. The distribution of stage was as follows: stage I (6%), stage II (21%), stage III (27%) and stage IV (46%). Counting data was analyzed by χ(2) test or Fisher's exact. Survival rates were calculated by Kaplan-Merier method. Statistical significance of differences in the cumulative survival curves was evaluated using the Log-rank test. Multivariate analysis was performed by Cox proportional hazard model.

RESULTSAll patients underwent primary tumor radical resection, 39 patients (75%) received postoperative radiation. The regional recurrence rate was 37% and distant metastasis rate was 21%. The 5-, 10-year cumulative local control rate were 68% and 63% respectively. The 5-, 10-year cumulative distant control rate were 86%, 68% respectively. The 5-, 10-year tumor specific survival rates were 70% and 54% respectively. Multivariate analysis showed that T stage, lymph node metastasis and perineural invasion were relevant to the tumor specific survival of ACC in minor salivary glands.

CONCLUSIONSRecurrence and metastasis were the main cause of treatment failure of ACC in minor salivary glands. T stage, lymph node metastasis and perineural invasion were the independent prognostic factors of ACC in minor salivary glands. Radical surgery and reasonably postoperative radiotherapy were the main treatment strategy.

Adult ; Aged ; Carcinoma, Adenoid Cystic ; pathology ; radiotherapy ; secondary ; surgery ; Cobalt Radioisotopes ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; secondary ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Particle Accelerators ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Salivary Gland Neoplasms ; pathology ; radiotherapy ; surgery ; Salivary Glands, Minor ; Survival Rate ; Young Adult

OBJECTIVETo analyze the clinicopathologic features of salivary malignant pleomorphic adenoma (MPA) (the subtype of the malignant component was classified as non-specific adenocarcinoma).

METHODSThe clinical and pathological characteristics of 115 salivary gland tumors histologically diagnosed as MPA were analyzed.

RESULTSIn all the 65 MPA cases, there were 58 male and 7 female patients, and the mean age was 57 years (from 23 to 83). Sixty-one tumors were located in major salivary glands, and 4 in minor. Histologically the malignant components of 39 tumors were high-grade, 14 intermediate-grade, and 12 low-grade. Thirty-seven tumors were invasive carcinoma, 13 minimally invasive, and 15 non-invasive. The high-grade tumors had positive correlation with the invasive carcinomas (P < 0.05). The invasive carcinomas had positive correlation with TNM clinical stage (P < 0.05). The invasive carcinoma and the high-grade tumor had correlation with cervical lymph node metastasis (P < 0.05).

CONCLUSIONSNon-specific adenocarcinoma are the most common malignant subtype in MPA. The invasive and the high-grade types are more likely to metastasize to cervical lymph node.

Adenocarcinoma ; pathology ; Adenoma, Pleomorphic ; pathology ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Retrospective Studies ; Salivary Gland Neoplasms ; pathology ; Salivary Glands ; pathology ; Salivary Glands, Minor ; pathology ; Young Adult

Adenocarcinoma ; pathology ; Adenoma ; pathology ; Carcinoma, Adenoid Cystic ; epidemiology ; genetics ; metabolism ; pathology ; Carcinoma, Basosquamous ; pathology ; DNA, Mitochondrial ; genetics ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Incidence ; Proto-Oncogene Proteins c-kit ; metabolism ; Salivary Gland Neoplasms ; epidemiology ; genetics ; metabolism ; pathology ; Salivary Glands, Minor ; pathology ; beta-Defensins ; genetics

AIMTo detect the expression of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) in salivary adenoid cystic carcinoma (SACC) tissues, as well as to determine the correlation between growth factor expression and prognosis in SACC.

METHODOLOGYMedical records of 63 patients surgically treated for SACC between January 1988 and October 2005 were reviewed. Immunohistochemistry was performed to examine the expression of NGF and VEGF in tumor tissues. Kaplan-Meier analysis and Cox's proportional hazard regression model were applied to assess predictors of survival.

RESULTSNGF and VEGF were overexpressed in SACC tissues, compared with those in normal salivary tissues (P < 0.05), and the staining intensity of these two factors was stronger in groups of solid subtype, advanced TNM stage, perineural invasion and recurrence. Patients with high-expression of NGF and VEGF, solid subtype, advanced stage, perineural invasion, recurrence and extended resection alone had worse survival rates (P < 0.05).

CONCLUSIONNGF and VEGF are expressed increasingly in the tissues of SACC cases with invasion and metastasis. NGF expression and VEGF expression are independent

Adult ; Aged ; Carcinoma, Adenoid Cystic ; pathology ; surgery ; Cranial Nerves ; pathology ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; pathology ; Neoplasm Staging ; Nerve Growth Factor ; analysis ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Salivary Gland Neoplasms ; pathology ; surgery ; Salivary Glands ; pathology ; Salivary Glands, Minor ; pathology ; Survival Rate ; Vascular Endothelial Growth Factor A ; analysis ; Young Adult

INTRODUCTIONClear cell carcinoma is a rare low-grade carcinoma that almost exclusively occurs in the minor salivary glands. This tumour is one of the new additions in the recent World Health Organization (WHO) classification of salivary gland tumours.

CLINICAL PICTUREA 50- year-old woman presented with a gradually enlarging painless submucosal mass of 3 months' duration over the left side of the palate.

TREATMENT AND OUTCOMEA preoperative diagnosis of primary clear cell carcinoma of salivary gland with focal surface epithelial dysplasia was rendered after thorough clinical examination to rule out renal origin. The lesions were excised with wide surgical margins and 3 years into the postoperative period, the patient was disease-free.

CONCLUSIONWe report a case of clear cell carcinoma of intra-oral minor salivary gland and draw comparisons with metastatic clear cell carcinoma of renal origin.

Adenocarcinoma, Clear Cell ; pathology ; surgery ; Female ; Humans ; Middle Aged ; Salivary Gland Neoplasms ; pathology ; surgery ; Salivary Glands, Minor