The oncofetal protein IMP3 is an indicator of early recurrence and poor outcome in mucoepidermoid carcinoma of salivary glands

Objective: Mucoepidermoid carcinoma(MEC) is the most common primary malignancy of the salivary glands. Insulin-like growth factor-II m RNA-binding protein-3(IMP3) is an important prognostic factor in some cancers and a tool that differentiates between benign and malignant pancreatic lesions. This study aimed to identify a relationship between the expression of IMP3 and the outcome of salivary gland MEC, as well as to differentiate MEC from pleomorphic adenoma(PA).Methods: Tissue specimens from 70 cases of salivary gland MEC, 40 cases of PA, and 10 cases with normal salivary gland were examined immunohistochemically for IMP3. The association among the expression of IMP3, clinicopathological characteristics and patient's survival was assessed.Results: IMP3 was present in 51.4% of MEC but absent in PA and normal salivary gland tissues. IMP3 expression was associated with age > 60 years, submandibular gland tumors, tumor size > 4 cm, high-grade tumors, lymph node metastasis, involvement of surgical margins, perineural invasion, distant metastasis, advanced TNM stage, tumor relapse, and death(P<0.05). Increased expression of IMP3, tumors of the submandibular gland, and lymph node metastasis were independent prognostic factors of disease-free survival(DFS). In addition, IMP3 was a strong predictor of overall survival(OS) together with distant metastasis and intermediate and high-grade tumors.Conclusions: IMP3 expression is highly important in evaluating the outcome of MEC. IMP3 can be used to differentiate MEC from PA of salivary glands.

Influence of the Radiation Dose to Salivary Glands on Xerostomia in Patients with Head and Neck Carcinomas

Purpose: Investigation of the influence of radiation dose to salivary glands on xerostomia in patients with head and neck cancers. Methods: From October 2002 to December 2011, 548 patients with head and neck carcinomas were treated in our department using intensity modulated radiotherapy (IMRT). 325 patients were eligible for analysis more than 1 year after irradiation. Xerostomia was evaluated according to the criteria of Radiation Therapy and Oncology Group (RTOG) and xerostomia related questionnaire. For statistical analysis grade 1 and 2 were recorded as mild and grade 3 and 4 as severe xerostomia. The dosimetric values for absolute mean dose, biological equivalent mean dose (EQD2), the relative organ volume not exceeding 20 Gy, 25 Gy and 30 Gy (V20, V25, V30) for all 4 major salivary glands or for both parotid glands only were used for analysis. V20 revealed the best discrimination between both patient groups (with vs. without xerostomia), compared to parameters V25 and V30. Therefore the volume of the salivary glands receiving less than 20 Gy (V 20Gy) was analyzed additionally. Mann-Whitney-U-test, Kruskal-Wallis-test and logistic regression were used in statistical analysis. Results: A TD 50 can be determined for the occurrence of xerostomia more than one year after radiotherapy for both parotid glands of 19.3 Gy for the mean dose absolute, 11.2 Gy for the mean dose EQD2, 38.2% for V20, 26.8% for V25, 18.7% for V30, 34.9 ml for V 20Gy. For all major salivary glands theses values were 25.7 Gy for the mean dose absolute, 15.6 Gy for the mean dose EQD2, 51.3% for V20, 41.1% for V25, 33.9% for V30 and 34.8 ml for V 20Gy. Conclusions: The identification of a tolerance dose for the salivary glands for treatment planning appears to be difficult, as the dose-response correlation only shows a flat slope. Additionally, a large interindividual variability seems to exist. We could not found any threshold dose for development of xerostomia.

Overall and cause-specific survival for mucoepidermoid carcinoma of the major salivary glands:Analysis of 2210 patients

BACKGROUND Mucoepidermoid carcinoma(MEC)is a rare malignancy of the head and neck;however,it accounts for a majority of the tumors of the salivary glands.This study used a national population-based registry to describe the pre-treatment and treatment-related prognostic factors that influence survival in patients with MEC of the major salivary glands.To our knowledge,this is the largest populationbased study examining predictors of both overall and cause-specific survival of MEC of the major salivary glands.AIM To identify prognostic factors influencing overall survival(OS)and cause-specific survival(CSS)of patients with MEC of the major salivary glands.METHODS We used the Surveillance,Epidemiology and End-Results Database of the National Cancer Institute to investigate a variety of factors that could influence survival of patients diagnosed with mucoepidermoid carcinoma of the major salivary glands.A total of 2210 patients diagnosed with MEC of the major salivary glands during the years of 1975-2016 were studied.The primary endpoints were OS and CSS.Cox regression analysis was used to perform univariate and multivariate analyses of clinical variables such as age at diagnosis,diagnosis year,sex,race,tumor size,stage,grade,treatment with or without surgical excision,and adjuvant radiotherapy treatment.RESULTS A total of 2210 patients diagnosed with MEC of the major salivary glands met inclusion criteria.In this study,95%of patients underwent surgical excision and 41%received adjuvant radiation therapy.Median OS time for Grade I,II,and III/IV was 401 mo(±48.25,95%CI),340 mo(±33.68,95%CI)and 55 mo(±11.05,95%CI),respectively.Univariate analysis revealed that lack of surgical excision was associated with decreased OS[hazard ratio(HR)4.26,P<0.0001]and that patients with localized disease had improved OS compared to both regional and distant disease(HR 3.07 and 6.96,respectively,P<0.0001).Additionally,univariate analysis demonstrated that male sex,age over 50 at diagnosis,Grade III tumors,and increasing tumor size were associated with worsened OS(P<0.0006).Univariate analysis of CSS similarly revealed that lack of surgical excision and Grade III carcinoma conferred decreased CSS(HR 4.37 and 5.44,respectively,P<0.0001).Multivariate analysis confirmed that increasing age,in 10-year age bands,advanced tumor stage,increasing tumor size,Grade III carcinoma,male sex,and lack of surgical excision were associated with a statistically significant decrease in OS and CSS(P<0.04).Of note,multivariate analysis revealed that the use of adjuvant radiation therapy was not associated with improved OS or CSS.CONCLUSION Multivariate analysis demonstrated increasing age,advanced tumor stage,increasing tumor size,Grade III carcinoma,male sex,and lack of surgical excision were associated with decreased OS and CSS(P<0.04).

Partial Characterization of Thrombin Inhibitor(s) Derived from Salivary Glands of the Tick, <i>Hyalomma dromedarii</i>, and Related Anti-Cancer Potential

A long-term blood feeder, like the Hyalomma dromedarii tick, requires extended control over all hemostatic defense mechanisms generated by the host during feeding, including blood coagulation. To overcome this, ticks have evolved numerous molecules that target proteases in the blood coagulation cascade. New insights into the role of clotting factors in the development and progression of cancer have identified anticoagulant treatment as a potential therapeutic approach. In this context, the present work assessed the anticoagulation activities of crude and fractionated salivary gland extract (SGE) prepared from semi-fed H. dromedarii females. Additionally, the antitumor effects of the potent anti-thrombin fractions were determined against colon cancer (Caco-2) and normal skin (HFB4) cells. Crude SGE significantly prolonged clotting time in prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT) assays and inhibited thrombin in FII-activity assay. Using anion-exchange chromatography, the fractions that strongly inhibited thrombin (3.A4 and 3.A5) were eluted. Both fractions prolonged the aPTT and TT clotting times and reduced the activity of FII significantly. The protein profiles of both fractions indicated the presence of a single polypeptide band of about 99 kDa. Regarding anti-cancer potential of the tested fractions, Caco-2 cells showed reduced viability with obvious morphological changes, induced apoptosis and a reduced level of vascular endothelial growth factor (VEGF). G2/M cell cycle arrest was observed only in 3.A5-treated cells. No cytotoxic effects were observed in HFB4 cells. These results demonstrated the potential of tick-derived anticoagulants, specifically thrombin inhibitors, as effective tools in colorectal cancer treatment. Further purification of the effector molecule(s) is required to fully characterize their structures and mechanisms of action.

Evaluation of P53 in Salivary Glands Tumors among a Syrian Sample

Objective： to evaluate the expression of P53 in salivary glands tumors among a Syrian sample. Material and methods： a retrospective analysis of gross and light microscopic features 50 salivary glands tumors that were treated and diagnosed at Almoasat hospital, the main hospital in Damascus. Only benign salivary glands tumors were included in this study, mainly pleomorphic adenoma and warthin＇s tumor. Results： 158 cases were studied from 2009 to 2016. Pleomotphic adenoma was the most occurring tumor （47.7%）, followed by Warthin tumor （30.9%） and mucoepidermoid carcinoma （6.1%）. Lesions of in minor salivary glands compromised （11.03%）. Only pleomorphic adenoma and warthin＇s tumor were included in the practical part of the study. All specimens showed a total negativity for P53 when they were studied under the light microscope. Conclusion： the result of this study agreed with some previously studies in other countries and was not similar to others in other countries. No differences were observed as to the type of the tumor. These results could be related to racial factors.

Salivary Glands Tumors： A Clinicopathological Study about the Incidence and Distribution of Salivary Glands Tumors among a Syrian Population Amirah Alnour

Objective： to investigate the clinicopathologic characters of salivary glands tumors in Damascus, Syria. Material and methods： a retrospective study on salivary glands tumors diagnosed at Almoasat hospital, the main hospital in Damascus, from 2009 to 2016. We measured the data related to patient age, gender, tumor site and the histopathologic diagnosis. Results： out of 158 cases over eight years, 62.2% was benign tumors, 9.4% was malignant tumors and 28.4% was inflammatory lesions. Pleomotphic adenoma was the most occurring tumor （47.7%）, followed by Warthin tumor （30.9%） and mucoepidermoid carcinoma （6.1%）. Lesions in minor salivary glands compromised （11.03%）. The peak ages of incidence were the third and fourth decades （38.35%）. A slight predilection for females was observed. Conclusion： the results of this study are similar to the previous studies in other countries. However differences were observed as to the frequencies of histopathologic types. These differences could be attributed to racial factor and the latest five years of war in Syria.

Pleomorphic Adenoma of the Hard and Soft Palate: A Case Presentation and Literature Review of Minor Salivary Gland Neoplasms

Introduction: Minor salivary gland tumors are relatively rare, but have a higher chance of malignancy than major salivary gland tumors. The palate appears to be the most commonly involved site. The most frequent benign tumor is the pleomorphic adenoma. Case report: We report a case of a pleomorphic adenoma, which occurred in the hard and soft palate of a 34-year-old female and presented as an asymptomatic slow growing, painless mass. The patient was successfully treated with surgical excision. Discussion: Minor salivary gland tumors should be considered in the differential diagnosis of oral cavity and especially palate tumors. A histological examination is necessary due to the high percentage of malignancy.

Autoimmune pancreatitis with IgG4-positive plasma cell infiltration in salivary glands and biliary tract

A 62-year-old male was referred to our hospital because of liver dysfunction, diffuse pancreatic swelling, and trachelophyma. At admission, the patient was free of pain. Physical examination showed enlarged and palpable bilateral submandibular masses, but no palpable mass or organomegaly in the abdomen. Laboratory findings were as follows： total protein 90 g/L with γ-globulin of 37.3% （33 g/L）, total bilirubin 4 mg/L, aspartate aminotransferase 39 IU/L, alanine aminotransferase 67 IU/L,γ-glutamyl transpeptidase 1 647 IU/L, and amylase 135 IU/L. Autoantibodies were negative, and tumor markers were within the normal range. Serum IgG4 level was markedly elevated （18 900 rag/L）. Computed tomography （CT） showed diffuse swelling of the pancreas and dilatation of both common and intra-hepatic bile ducts. Endoscopic retrograde pancreatography （ERP） revealed diffuse irregular and narrow main pancreatic duct and stenosis of the lower common bile duct. Biopsy specimens from the pancreas, salivary gland and liver showed marked periductal IgG4-positive plasma cell infiltration with fibrosis. We considered this patient to be autoimmune pancreatitis （AIP） with fibrosclerosis of the salivary gland and biliary tract, prescribed prednisolone at an initial dose of 40 mg/d. Three months later, the laboratory data improved almost to normal. Abdominal CT reflected prominent improvement in the pancreatic lesion. Swelling of the salivary gland also improved. At present, the patient is on 10 mg/d of prednisolone without recurrence of the pancreatitis. We present here a case of AIP with fibrosclerosis of salivary gland and biliary tract.

AN UNUSUAL TYPE OF SOLID CARCINOMA OF SALIVARY GLANDS: A CLINICOPATHOLOGIC AND IMMUNOHISTOCHEMICAL STUDY

An unusual histologic type and low-grade malignancy of salivary gland (SG) carcinomas, namely solid carcinoma (SC), is reported. Histopathologic characteristics of 12 cases of the SC include (1) large solid nest structure, (2) isomorphic and blandness of the epithelial cells in cytoloogy, (3) squamous metaplasia and keratinization in different degrees. (4) infiltrative growth pattern. Immunohistochemical stainings reveal that the cells of the SCs are reacted positive with anti-cytokeratins 12 and 27, anti-S-100P, anti-EMA antibodies in different degrees, and negative with anti-desmin, anti-GFAP, anti-lysozyme antibodies. The positive reactions with anti-CEA, anti-actin, and anti-myoglobin are detected in a few individuals. Follow-up data show the recurrence rate and mortality of the SC are 73% and 18% respectively. The histogenesis of SC and differential diagnosis are also discussed in the paper.

Selective partial salivary glands sparing during intensity-modulated radiation therapy for nasopharyngeal carcinoma

Objective This study evaluated the dosimetric consequences of selective partial salivary gland sparing during intensity-modulated radiotherapy(IMRT) for patients with nasopharyngeal carcinoma(NPC).Methods Ten patients with NPC were enrolled in the study.Two IMRT plans were produced for each patient:conventional(control) and partial salivary glands-sparing(treatment),with dose constraints to the entire parotid glands or partial salivary glands(including the parotid and submandibular glands,delineated with the adjacent distance of at least 0.5 cm between the glands and PTV,the planning target volume) in planning,respectively.Dosimetric parameters were compared between the two plans,including the V_(110%),V_(100%),V_(95%)(the volume covered by more than 110%,100%,or 95% of the prescribed dose),Dmin(the minimum dose) of PTV,homogeneity index(HI),conformity index(CI),and the mean dose and percentage of the volume receiving 30 Gy or more(V_(30)) for the parotid glands and submandibular glands.Results Treatment plans had significantly lower mean doses and V_(30) to both the entire parotid glands and partial parotid glands than those in control plans.The mean doses to the partial submandibular glands were also significantly lower in treatment plans than in control plans.The PTV coverage was comparable between the two plans,as indicated by V_(100%),V_(95%),Dmin,CI,and HI.The doses to critical structures,including brainstem and spinal cord,were slightly but not significantly higher in treatment plans than in control plans.Conclusion A selective partial salivary gland-sparing approach reduces the doses to parotid and submandibular glands during IMRT,which may decrease the risk of post-radiation xerostomia while not compromising target dose coverage in patients with NPC.

30-bp DELETION IN LATENT MEMBRANE PROTEIN 1 (LMP-1) ONCOGENE IN LYMPHOEPITHELIAL CARCINOMA OF SALIVARY GLANDS

Objective: To investigate the 30 bp deletion in LMP-1 in lymphoepithelial carcinoma of salivary glands, and to clarify the deletion rate. Methods: 46 cases of LEC were subjected to PCR examination for the 3?terminal region of LMP-1 gene, in order to observe the 30 bp deletion. To reduce the influence of unsuccessful DNA extraction from paraffin-embedded tissue sections, a bactin PCR was performed at the same time. Additionally, DNA sequencing was performed on 1 case without deletion and 1 case with deletion. Results: 4 of 46 specimens were proved to contain no suitable DNA sample by bactin gene amplification. In the remaining 42 cases, LMP-1 DNA was detected in 35/42 (83.3%) LEC cases. Two kinds of PCR products were found in these 35 cases after further DNA sequencing. 31 cases (88.6%) carried 316 bp product and 4 cases (11.4%) carried 286 bp product. Conclusion: Some LECs of salivary glands carry del-LMP-1. In our study, the deletion rate was 11.4% (4/35).

Study of the expression and transfer of VEGF in salivary glands and its saliva content in rats

Objective: To study the feasibility to use vascular endothelial growth factor (VEGF) gene therapy for salivary glands, and observe the saliva content of VEGF. Methods: VEGF cDNA was cloned into eukaryotic expression vector pBKCMV, and VEGF gene was transferred into rat maxillary glands mediated by lipofectin AMINE. The expression of VEGF gene was observed with RT-PCR, and the saliva content of VEGF was determined with ELISA. Results: The expression of VEGF gene and the saliva content of VEGF were significantly higher in the experimental group than in the control groups. The 2 parameters reached the peak 2-3 d after treatment and mintained the high level for 5 d. Conclusion: One findings show that VEGF can express stably and persistently in salivary glands. Meanwhile, the saliva content of VEGF is increased, which suggest that VEGF gene therapy might be a new method to promote the healing of oral mucosal ulcers.

STUDIES OF TISSUE CULTURE ON THE ADENOID CYSTIC CARCINOMA OF SALIVARY GLANDS

In this paper, the authors gave a synthetic report about sutdies of tissue culture on adenoid cystic carcinomas from human salivary glands. It includes the process of establishment of Acc-2 and Acc-3 cell lines, observations to the cellular morphostructures, chromosome analysis, proliferative kinetics and some cellular physiological functions. All of these observations confirm that two cell lines have obvious malignant natures, epithelial and glandulous cellular features as well as. Both of cell lines have provided the useful experimental models in vitro for research on histogenesis and biological behaviours at adenoid cystic carcinoma and seeking new methods of clinical treatment.

Tumours of salivary glands in the stomatology and maxillo-facial surgery unit at the university hospital centre —Yalgado Ouédraogo

The aim of this study was to contribute to strengthening the efficiency in the treatment of the salivary gland tumours in the Stomatology and Maxillo-facial surgery service at the University Hospital Centre/Yalgado OUEDRAOGO of Ouagadougou. It has been a retrospective and descriptive study covering seven (7) years [January 2006-December 2012] on epidemiology and the treatment of 54 cases of the salivary glands tumours histologically confirmed. Benign tumours (non-malignant tumours were prevalent (61.11% of cases). The annual incidences were 4.71 cases for non malignant tumours and 3 cases for malignant tumours. The average age was 34-45 years for non malignant tumours and 44-33 years for malignant ones. In both groups, the tumour was discovered lately with an average 32-48 months before consulting in case of non malignant tumours and 18-29 months for malignant tumours. The location of non malignant tumours was very often the parotid (42.42%), under mandible gland (27.28%). Malignant tumours very often concerned the parotid (76.18%) and the under mandible gland (14.29%). The histology has revealed that pleomorphic adenoma was the leading type of non-malignant tumours (93.94% of cases) whereas carcinoma was predominant in malignant tumours (80.95% of cases). Long term track keeping was difficult and it has been complicated by the loss of contact with some patients. The low living standard, the time wasted before consulting, limited human resources and therapeutic means constitute handicaps to the treatment in our African context.

Gross Tumour of Minor Salivary Glands in HIV Sero-Positive Patient

Tumours of minor salivary glands are rare. We report the case of a 58-year-old HIV positive woman with a palatal adenocarcinoma evolving for 15 years, followed by a literature review. The case enlightens on the deleterious effect of delayed specialist consultation, which in our context is multifactorial in origin.

DETECTION OF HUMAN HERPESVIRUS 6(HHV-6) DNA IN SALIVARY GLANDS BY THE POLYMERASE CHAIN REACTION

To assess the presence of HHV-6-Specific DNA in human salivary glands, eighteen specimens of salivary gland tissue were investigated using the polymerase chain reaction. Eight of nine parotid glands, five of seven submandibular glands and one of two sublingual glands were found to have amplification of the HHV-6-specific sequence. The findings suggest that salivary gland tissue is one of the potential sites for HHV-6 persistence following primary infection and that saliva is a vehicle for transmission of the virus.

Myoepithelial carcinoma of the salivary glands: behavior and management

To investigate the biological behavior and proper management of myoepithelial carcinomas of salivary glands Methods Twenty seven cases of myoepithelial carcinoma of salivary glands were retrospectively studied and their detailed clinical and follow up data were presented Results The subjects consisted of 17 men and 10 women aged 16 to 73 years (mean age: 51 years) The parotid gland was the most common site (n=14) of cancer Clinical features included extensive local growth, invasion of the surrounding tissues, infrequent cervical lymph node metastasis but high rates of distant metastasis, frequent/multiple recurrences and poor prognosis Conclusions Myoepithelial carcinomas of the salivary gland should be classified as high grade malignancies Early and radical surgery with close follow up are essential for achieving favorable outcomes Radiotherapy appears to be non sensitive and elective neck dissection is generally unnecessary

Effects of Chinese herbs on salivary fluid secretion by isolated and perfused rat submandibular glands

AIM： TO determine whether Chinese herbs （CHs） relieve xerostomia （dry mouth） by increasing salivary secretion. METHODS： The submandibular glands of Wistar rats were surgically isolated and perfused arterially with buffered salt solution. After control perfusion, recording started 5 min prior to the start of stimulation. After fluid secretion was induced by 0.2 μmol/L carbamylcholine （CCh） in the perfusate for 10 min, Chinese herb （CH） was added in the perfusion for 5 min. CCh was then overloaded at 0.2 μmol/L in the perfusion for 20 min. The volume of salivary fluid secretion was recorded by a computer-controlled balance system. RESULTS： Saliva secretion formed an initial ephemeral peak at 30 s followed by a gradual increase to a sustained level. CH alone induced no or little saliva in all types of CH selected. During perfusion with CH,overloading of CCh promoted fluid secretion in 1S of 20 CHs. This promotion was classified into four patterns, which were eventually related to the categories of CH： Overall sustained phase was continuously raised （Yin-nourishing, fluid production-promoting and heatclearing agents）; The sustained secretion rose to reach a maximum then decreased （Qi-enhancing agent）; Sustained secretion rose to reach the highest maximum and was then sustained with a slight decline （swelling-reducing, phlegm-resolving and pus-expelling agents）; Stimulation of salivary secretion without any added stimulants. Addition of CCh raised the fluid secretion to reach the highest maximum then sharply decreased to a lower sustained level （blood activating agent）. CONCLUSION： The present findings lead to the conclusion that various CHs have different promotional effects directly on the salivary gland.

An inhibitor selective for collagen-stimulated platelet aggregation from the salivary glands of hard tick Haemaphysalis longicornis and its mechanism of action

Soluble materials of salivary glands from Haemaphysalis longicornis were found to inhibit collagen, ADP, and thrombin- stimulated platelet aggregation. One inhibitory component was purified to salivary gland homogeneity by a combination of gel filtration, ion-exchange, and C8 reverse phase HPLC. The purified activity, named longicomin, is a protein of molecular weight 16 000 on SDS-PAGE under both reduced and nonreduced conditions. Collagen-mediated aggregation of platelets in plasma and of washed platelets (IC50 was approximately 60 nmol/L) was inhibited with the same efficacy. No inhibition of aggregation stimulated by other effectors, including ADP, arachidonic acid, thrombin, risto-cetin, calcium ionophore A23187, thromboxane A2 mimetic U46619 and 12-0-phorbol-13-myristate acetate, was observed . Longiconin had no effect on platelet adhension to collagen. Not only platelet aggregation but also release reaction, and increase of intracellar Ca2+ level of platelets in response to collagen were completely eliminated by longicomin . Increasing amounts of collagen are able to overcome the inhibition of aggregation by longicomin, indicating that longicomin probably shares with collagen a common receptor. In addition, collagen fibers did not emit fluorescence after incubation with isothocyanate-conjugated longicomin, indicating that longicomin did not bind directly to collagen fibers. The identification and isolation of longicomin demonstrates the existence of a new type of platelet inhibitor that should be useful to better understand the mechanism of collagen stimulation of platelets.

The expression of Twist in salivary adenoid cystic carcinoma and its clinicopathological significance

Objective:The purpose of this study was to investigate the expression of Twist in salivary adenoid cystic carcinoma (SACC) and the relations between Twist expression and the clinicopathological characteristics. Methods: The expression of Twist was examined immunohistochemically in 48 cases of SACC, 18 of pleomorphic adenoma and 10 of normal parotid gland. The relationship between Twist expression in SACC and the clinicopathological factors was analyzed. Results: Twist expression was significantly higher in SACC tissues compared with pleomorphic adenomas and normal parotid gland tissues (P<0.05). Twist expression levels in SACC were significantly associated with histological type, perineural invasion, postoperative recurrence, and distant metastasis (P<0.05), rather than age, gender, tumor site, tumor size, or clinical staging (P>0.05). Conclusion: Twist expression may be associated with tumor cell differentiation, perineural invasion and metastasis of SACC. Twist expression is a potential prognostic factor for disease survival of SACC.