Antimicrobial Activity in Chitosan-Treated Prosthetic Materials: A Systematic Review.

OBJECTIVE: The antimicrobial effect of prosthetic materials treated with chitosan was systematically reviewed. METHODS: The searches were carried out on PubMed/Medline, Scopus, ISI Web of Science, LILACS, Embase, and Open Grey with searches performed in March 2022. Selection of in vitro studies, data extraction and risk of bias analysis were performed following the PRISMA guidelines and registered at the Open Science Framework. The evaluated prosthetic materials corresponded to PMMA and tissue conditioner, treated with chitosan. RESULTS: After evaluating the eligibility criteria, 11 articles were included for the qualitative synthesis. The evaluated prosthetic materials corresponded to PMMA (n=8) and tissue conditioner (n=3). All studies performed the incorporation of chitosan in the tissue conditioner (n=3). Regarding PMMA, the use of chitosan as a denture cleanser was the most used (n=3), followed by incorporation (n=2), multilayers coating onto PMMA (n=2) and denture adhesive for PMMA (n=1). Chitosan has antimicrobial activity and is effective in the treatment of prosthetic materials in most studies, but it depends on some factors, such as the treatment method, the type and characteristics of the chitosan, the microorganism evaluated, and its form of organization. CONCLUSION: Chitosan showed highly antimicrobial activity and was effective when used in prosthetic materials.

Glucocorticoid-induced adrenal insufficiency: an uncommon cause of hypercalcaemia.

Summary: Long-term use of exogenous glucocorticoids leads to the suppression of the hypothalamic-pituitary-adrenal axis. Therefore, if the glucocorticoid is withdrawn abruptly, patients will develop adrenal insufficiency. Hypercalcaemia is a rare but well-known complication of adrenal insufficiency. However, hypercalcaemia is a rare presentation of glucocorticoid-induced adrenal insufficiency (GI-AI). A 62-year-old patient with a past history of diabetes mellitus, ischaemic heart disease, stroke, hypertension and dyslipidaemia presented with polyuria, loss of appetite, malaise and vomiting for a duration of 2 months. His ionized calcium level was high at 1.47 mmol/L. Intact parathyroid hormone was suppressed (4.3 pg/mL) and vitamin D was in the insufficient range (24.6 ng/mL). Extensive evaluation for solid organ or haematological malignancy including contrast-enhanced CT chest, abdomen, pelvis, multiple myeloma workup and multiple tumour markers were negative. His synacthan-stimulated cortisol was undetectable thus confirming adrenal insufficiency. His adrenocorticotrophic hormone level was 3.82 pg/mL (4.7-48.8) excluding primary adrenal insufficiency. His MRI brain and other pituitary hormones were normal. Further inquiry revealed that the patient had taken over-the-counter dexamethasone on a regular basis for allergic rhinitis for more than 2 years and had stopped 2 weeks prior to the onset of symptoms. Therefore, a diagnosis of GI-AI leading to hypercalcemia was made. The patient was resuscitated with intravenous fluids and replacement doses of oral hydrocortisone were started with a plan of prolonged tailing off to allow the endogenous adrenal function to recover. His calcium normalized and he made a complete recovery. Learning points: Long-term use of glucocorticoids leads to the suppression of the hypothalamic-pituitary-adrenal axis. If the glucocorticoid is withdrawn abruptly, patients will develop adrenal insufficiency which is known as glucocorticoid-induced adrenal insufficiency. Adrenal insufficiency should be considered in the differential diagnosis of parathyroid hormone-independent hypercalcaemia. A thorough clinical history is of paramount importance in arriving at the correct diagnosis.

Bilateral Leydig Cell Hyperplasia: A Rare Cause of Postmenopausal Hirsutism.

BACKGROUND: Postmenopausal hirsutism could be due to a myriad of causes, including ovarian and adrenal tumours, ovarian hyperthecosis, exogenous androgens, and Cushing's syndrome. We report a patient who was found to have a rare cause of postmenopausal hirsutism. Case Presentation. A 64-year-old postmenopausal woman with a history of hypertension, thyrotoxicosis, and poorly controlled diabetes on multiple oral hypoglycaemic agents presented with gradual onset progressive excessive hair growth without any virilizing features. On examination, she did not have Cushingnoid features or clitoromegaly. Her hirsutism was quantified with Ferriman-Gallwey score which was 9. Her biochemical evaluation showed elevated testosterone levels with normal DHEAS, ODST, 17-OHP, and prolactin. Low-dose dexamethasone suppression test did not suppress testosterone more than 40%. Contrast-enhanced CT of the adrenal and pelvis did not show any adrenal or ovarian mass lesions. Transvaginal ultrasound scan showed bilateral prominent ovaries only. Combined adrenal and ovarian venous sampling was carried out to localize the source of excess androgen, but only the left adrenal vein was successfully cannulated which showed suppressed testosterone level compared to periphery. The patient underwent total abdominal hysterectomy and bilateral salphingo oophorectomy, and her testosterone level normalized postoperatively. Her glycaemic control improved. Histology showed evidence of bilateral diffuse ovarian Leydig cell hyperplasia. CONCLUSION: Evaluation of postmenopausal hirsutism needs careful history and examination followed by biochemical evaluation and imaging. While adrenal and ovarian venous sampling can help to arrive at a diagnosis, it is a technically demanding procedure with low success rates even at centers of excellence. Therefore, in such situations, bilateral oophorectomy may be the best course of action which will give the histological confirmation of the diagnosis. Successful treatment of hyperandrogenism can result in improvement of glycaemic control. Bilateral diffuse Leydig cell hyperplasia is a rare but important cause of postmenopausal hirsutism.

A patient with extensive cerebral calcification due to pseudohypoparathyroidism: a case report.

BACKGROUND: Pseudohypoparathyroidism(PHP) is a heterogeneous group of disorders due to impaired activation of c AMP dependant pathways following binding of parathyroid hormone (PTH) to its receptor. In PHP end organ resistance to PTH results in hypocalcaemia, hyperphosphataemia and high PTH levels. CASE PRESENTATION: A 59 year old male presented with a history of progressive impairment of speech and unsteadiness of gait for 1 week and acute onset altered behavior for 1 day and one episode of generalized seizure. His muscle power was grade four according to MRC (medical research council) scale in all limbs and Chovstek's and Trousseau's signs were positive. Urgent non contrast computed tomography scan of the brain revealed extensive bilateral cerebral and cerebellar calcifications. A markedly low ionized calcium level of 0.5 mmol/l, an elevated phosphate level of 9.5 mg/dl (reference range: 2.7-4.5 mg/dl) and an elevated intact PTH of 76.3 pg/l were noted. His renal functions were normal. His hypocalcemia was accentuated by the presence of hypomagnesaemia. His 25 hydroxy vitamin D level was only marginally low which could not account for severe hypocalcaemia. A diagnosis of pseudohypoparathyroidism without phenotypic defects, was made due to hypocalcaemia and increased parathyroid hormone levels with cerebral calcifications. The patient was treated initially with parenteral calcium which was later converted to oral calcium supplements. His coexisting Vitamin D deficiency was corrected with 1αcholecalciferol escalating doses. His hypomagnesaemia was corrected with magnesium sulphate parenteral infusions initially and later with oral preparations. With treatment there was a significant clinical and biochemical response. CONCLUSION: Pseudohypoparathyroidism can present for the first time in elderly resulting in extensive cerebral calcifications. Identification and early correction of the deficit will result in both symptomatic and biochemical response.

Semantic Data Integration Service for eHealth Applications.

Technologies for health have been receiving considerable attention with the popularization of devices for internet access. The Internet can be seen as a repository of knowledge due to its large amount of available information; however, on the other hand, in the midst of this vast amount of content, there is information either scientifically inaccurate or incomplete. This work presents a semantic integration service to provide information of diabetes from medical databases to eHealth applications.

Prevalence, patterns, and associations of dyslipidemia among Sri Lankan adults-Sri Lanka Diabetes and Cardiovascular Study in 2005-2006.

BACKGROUND: Dyslipidemia is a major risk factor for cardiovascular disease. Prevalence patterns and determinants of dyslipidemia in Sri Lanka are unkown. OBJECTIVES: We aimed to determine the prevalence and correlates of dyslipidemia among Sri Lankan adults. METHODS: A nationally representative sample was recruited by multistage random cluster sampling in Sri Lanka Diabetes and Cardiovascular Study, a cross-sectional study. Data collected by an interviewer-administered questionnaire, physical examination, anthropometric measurements lipid analysis from take 12-hour fasting blood samples were used. RESULTS: Among 4451 participants 60.5% were women and mean age was 46 years. Mean (standard deviation) total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), triglycerides (TGs), and TC/HDLC levels were 206.7 mg/dL (±43.5), 46.8 mg/dL (±10.6), 135.5 mg/dL (±37.6), 121.7 mg/dL (±66.8), and 4.6 (±1.1), respectively. Women had higher mean TC, HDLC, LDLC, and TG values compared to men across all age groups. Mean TC, LDLC, and TGs increased with age in both genders; 77.4% of participants had some form of dyslipidemia. Low HDLC was the commonest type (49.6%) of dyslipidemia. Increasing age, female sex, living in urban sector, high body mass index, central obesity, diabetes, hypertension, insufficient physical activity, and smoking were associated with having some form of dyslipidemia. CONCLUSION: Three in four Sri Lankan adults have some form of dyslipidemia. Physical inactivity, obesity, hypertension, and diabetes are the leading modifiable risk factors.

Clinicopathological relevance of antithyroglobulin antibodies in low-risk papillary thyroid cancer.

OBJECTIVE: The extent of initial surgical management in papillary thyroid cancer (PTC) is controversial. We examined whether the presence of perioperative antithyroglobulin antibodies (TGA) could predict long-term recurrence and occurrence of adverse features among a homogenous group of patients with PTC. METHODS: The clinical features of patients with PTC treated at a single institution (Jewish General Hospital, McGill University, Montreal, Canada) were obtained from the medical records, and all clinicopathologic information was reviewed. Only low-risk PTC without clinical evidence of nodal disease before surgery and treated with 30 mCi of radioactive iodine was included in the study. RESULTS: The chart review retrieved 361 patients with a median follow-up of 85.0 months (Q25-Q75 73-98). Forty-two (11.6%) patients had presence of perioperative TGA. Perioperative TGAs were associated with present extrathyroidal extension (P=.005), unsuspected nodal disease (P=.001) and autoimmune thyroiditis (P<.0001). Overall, 17 (4.7%) patients experienced locoregional recurrence. Perioperative TGAs were a significant predictor of recurrence in univariable (P=.021) but not in multivariable analysis (P=.13). CONCLUSION: Presence of perioperative TGAs is associated with aggressive histological features and the presence of thyroiditis. Detection of TGA perioperatively may encourage surgeons to consider more extensive initial surgery.

Development and validation of a Diabetes Risk Score for screening undiagnosed diabetes in Sri Lanka (SLDRISK).

BACKGROUND: Screening for undiagnosed diabetes is not widely undertaken due to the high costs and invasiveness of blood sampling. Simple non-invasive tools to identify high risk individuals can facilitate screening. The main objectives of this study are to develop and validate a risk score for screening undiagnosed diabetes among Sri Lankan adults and to compare its performance with the Cambridge Risk Score (CRS), the Indian Diabetes Risk Score (IDRS) and three other Asian risk scores. METHODS: Data were available from a representative sample of 4276 adults without diagnosed diabetes. In a jack-knife approach two thirds of the sample was used for the development of the risk score and the remainder for the validation. Age, waist circumference, BMI, hypertension, balanitis or vulvitis, family history of diabetes, gestational diabetes, physical activity and osmotic symptoms were significantly associated with undiagnosed diabetes (age most to osmotic symptoms least). Individual scores were generated for these factors using the beta coefficient values obtained in multiple logistic regression. A cut-off value of sum = 31 was determined by ROC curve analysis. RESULTS: The area under the ROC curve of the risk score for prevalent diabetes was 0.78 (CI 0.73-0.82). In the sample 36.3 % were above the cut-off of 31. A risk score above 31 gave a sensitivity, specificity, positive predictive value and negative predictive value of 77.9, 65.6, 9.4 and 98.3 % respectively. For Sri Lankans the AUC for the CRS and IDRS were 0.72 and 0.66 repectively. CONCLUSIONS: This simple non-invasive screening tool can identify 80 % of undiagnosed diabetes by selecting 40 % of Sri Lankan adults for confirmatory blood investigations.

Survival and quality of life in oropharyngeal cancer patients treated with primary chemoradiation after salivary gland transfer.

OBJECTIVES: Salivary gland transfer surgery can reduce xerostomia in oropharyngeal squamous cell carcinoma patients undergoing primary chemoradiation. A potential drawback of salivary gland transfer is the treatment delay associated with the surgery, and its complications. This study aimed to determine whether the treatment delay affects patient survival and to evaluate patient quality of life after salivary gland transfer. METHODS: A retrospective analysis of 138 patients (salivary gland transfer group, n = 58; non-salivary gland transfer group, n = 80) was performed. Patient survival was compared between these groups using multivariate analysis. Salivary gland transfer patients were further evaluated for surgical complications and for quality of life using the head and neck module of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. RESULTS: Salivary gland transfer and non-salivary gland transfer patients had comparable baseline clinical characteristics. Salivary gland transfer patients experienced a median treatment delay of 16.5 days before chemoradiation (p = 0.035). Multivariate analysis showed that this did not, however, correspond to a survival disadvantage (p = 0.24 and p = 0.97 for disease-free and disease-specific survival, respectively). A very low complication rate was reported for the salivary gland transfer group (1.7 per cent). Questionnaire scores for the item 'xerostomia' were very low in salivary gland transfer patients. CONCLUSION: The treatment delay associated with salivary gland transfer surgery does not negatively affect patient survival. Oropharyngeal squamous cell patients have an excellent quality of life after salivary gland transfer.

Merkel cell carcinoma of the head and neck: poorer prognosis than non-head and neck sites.

BACKGROUND: Merkel cell carcinoma is a rare, aggressive neurocutaneous malignancy. This study investigated whether patients with Merkel cell carcinoma in the head and neck had poorer outcomes than patients with Merkel cell carcinoma located elsewhere. METHODS: A retrospective study was performed of patients with Merkel cell carcinoma treated at the Jewish General Hospital in Montréal, Canada, from 1993 to 2013. Associations between clinicopathological characteristics and disease-free and disease-specific survival rates were examined according to the Kaplan-Meier method. RESULTS: Twenty-seven patients were identified. Although basic clinicopathological characteristics and treatments were similar between head and neck and non-head and neck Merkel cell carcinoma groups, disease-free and disease-specific survival rates were significantly lower in the head and neck Merkel cell carcinoma group (log-rank test; p = 0.043 and p = 0.001, respectively). Mortality was mainly due to distant metastasis. CONCLUSION: Patients with head and neck Merkel cell carcinoma had poorer survival rates than patients with non-head and neck Merkel cell carcinoma in our study. The tendency to obtain close margins, a less predictable metastatic pattern, and/or intrinsic tumour factors related to the head and neck may explain this discrepancy.

Breast tumor classification in ultrasound images using neural networks with improved generalization methods.

Mammography, scintimammography and ultrasound images have been used to increase the specificity of breast cancer image diagnosis. Concerning breast cancer image diagnosis with ultrasound, some results found in the literature show better performance of morphological features in breast cancer lesion differentiation and that a reduced set of features shows a better performance than a large set of features. In this study we evaluated the performance of neural network classifiers, with different training stop criteria: mean square error, early stop and regularization. The last two criteria were developed to improve neural network generalization. Different sets of morphological features were used as neural network inputs. Training sets comprised of 22, 8, 7, 6, 5 and 4 features were employed. To select reduced sets of features, a scalar selection technique with correlation was used. The best results obtained for accuracy and area under the ROC curve were 96.98% and 0.98, respectively. The performance obtained with all 22 features is slightly better than the one obtained with a reduced set of features.

p16 (INK4a) has clinicopathological and prognostic impact on oropharynx and larynx squamous cell carcinoma

CDKN2A encodes proteins such as p16 (INK4a), which negatively regulate the cell-cycle. Molecular genetic studies have revealed that deletions in CDKN2A occur frequently in cancer. Although p16 (INK4a) may be involved in tumor progression, the clinical impact and prognostic implications in head and neck squamous cell carcinoma (HNSCC) are controversial. The objective of this study was to evaluate the frequency of the immunohistochemical expression of p16 (INK4a) in 40 oropharynx and 35 larynx from HNSCC patients treated in a single institution and followed-up at least for 10 years in order to explore potential associations with clinicopathological outcomes and prognostic implications. Forty cases (53.3%) were positive for p16 (INK4a) and this expression was more intense in non-smoking patients (P = 0.050), whose tumors showed negative vascular embolization (P = 0.018), negative lymphatic permeation (P = 0.002), and clear surgical margins (P = 0.050). Importantly, on the basis of negative p16 (INK4a) expression, it was possible to predict a probability of lower survival (P = 0.055) as well as tumors presenting lymph node metastasis (P = 0.050) and capsular rupture (P = 0.0010). Furthermore, increased risk of recurrence was observed in tumors presenting capsular rupture (P = 0.0083). Taken together, the alteration in p16 (INK4a) appears to be a common event in patients with oropharynx and larynx squamous cell carcinoma and the negative expression of this protein correlated with poor prognosis.

p16 (INK4a) has clinicopathological and prognostic impact on oropharynx and larynx squamous cell carcinoma.

CDKN2A encodes proteins such as p16 (INK4a), which negatively regulate the cell-cycle. Molecular genetic studies have revealed that deletions in CDKN2A occur frequently in cancer. Although p16 (INK4a) may be involved in tumor progression, the clinical impact and prognostic implications in head and neck squamous cell carcinoma (HNSCC) are controversial. The objective of this study was to evaluate the frequency of the immunohistochemical expression of p16 (INK4a) in 40 oropharynx and 35 larynx from HNSCC patients treated in a single institution and followed-up at least for 10 years in order to explore potential associations with clinicopathological outcomes and prognostic implications. Forty cases (53.3%) were positive for p16 (INK4a) and this expression was more intense in non-smoking patients (P = 0.050), whose tumors showed negative vascular embolization (P = 0.018), negative lymphatic permeation (P = 0.002), and clear surgical margins (P = 0.050). Importantly, on the basis of negative p16 (INK4a) expression, it was possible to predict a probability of lower survival (P = 0.055) as well as tumors presenting lymph node metastasis (P = 0.050) and capsular rupture (P = 0.0010). Furthermore, increased risk of recurrence was observed in tumors presenting capsular rupture (P = 0.0083). Taken together, the alteration in p16 (INK4a) appears to be a common event in patients with oropharynx and larynx squamous cell carcinoma and the negative expression of this protein correlated with poor prognosis.

Clinicopathological factors are predictors of distant metastasis from major salivary gland carcinomas.

The risk of distant metastasis of salivary gland cancers has usually been associated with histological type, tumour size, and site. The aim of this study was to evaluate a series of patients with major salivary gland carcinomas in order to identify potential risk factors associated with distant metastasis. 255 patients treated for major salivary gland carcinoma in Brazil from 1953 to 2004 were reviewed. Clinical and treatment data were obtained from the medical records and histological features reviewed. 57 (22%) of 255 patients had distant metastasis. The lungs were the most common metastatic site (40 cases, 65%) and adenoid cystic carcinoma the most frequent histological type involved (27 cases, 47%). The percentage of tumours in the submandibular, parotid, and sublingual glands that presented distant metastasis was 42%, 20%, and 17%, respectively. These results provide evidences that clinicopathological factors (tumour site and histology) are significant predictors of distant metastasis in patients with major salivary gland carcinomas.

ErbB receptors and fatty acid synthase expression in aggressive head and neck squamous cell carcinomas.

SUMMARY: Overexpression of ErbB receptors is frequent in head and neck squamous cell carcinomas (HNSCC) and seems to be correlated with tumor progression and metastasis. Fatty acid synthase (FASN), the key lipogenic enzyme responsible for the endogenous synthesis of fatty acids, is regulated by ErbB2 and overexpressed in several human malignancies. METHODS: This study was performed to examine the immunohistochemical expression patterns of ErbB1, ErbB2, ErbB3, ErbB4, and FASN in a tissue microarray, containing 33 representative areas from aggressive primary HNSCC (whose patients had distant metastasis), and 21 matched lung metastasis. RESULTS: Strong correlation among the expression of ErbB family receptors was found (ErbB1-ErbB2 P = 0.008, ErbB1-ErbB4 P = 0.018, EbB2-ErbB3 P = 0.001, ErbB2-ErbB4 P = 0.006, ErbB3-ErbB4 P=0.012) in the HNSCC. FASN expression was significantly associated with ErbB2 (P = 0.024). Lymphatic permeation was correlated with ErbB3 (P = 0.033) and histological grade with ErbB4 staining (P = 0.050). ErbB1 and ErbB2 were found mainly in patients with smoking habit (P = 0.011 and P = 0.027), and ErbB2 was associated with alcohol consumption and clinical stage (P = 0.014 and P = 0.031). Finally, FASN was overexpressed in lung metastasis, in comparison with matched HNSCC samples (P = 0.006). CONCLUSIONS: The results showed that high FASN immunohistochemical expression is a feature of HNSCC lung metastasis, and ErbB1-ErbB2, ErbB1-ErbB4, ErbB2-ErbB3, ErbB2-ErbB4, and ErbB3-ErbB4 expression levels are correlated in the respective primary tumors, being ErbB2 the preferred coexpression partner of all the other ErbB receptors.

[Molecular research methods in the detection of germinal mutations in hereditary colorectal cancer]. / Metodos de investigacion molecular en la deteccion de mutaciones germinativas en cancer colorrectal hereditario.

Colorectal cancer (CRC) is one of the main causes of death in South American countries. The hereditary forms of CRC are, familial adenomatous (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch Syndrome (LS), which is the most common form. The detection of mutations in the DNA repair genes (MMR) and in the APC genes enables the development of prevention strategies. Some of these methods for molecular diagnosis are applied in research and the detection of mutations of these genes, such as the partial thromboplastin time test (PTT), the single strand conformational polymorphism test (SSCP), the Denaturing High Performance Liquid Chromatography test (DHPLC) and the Polymerase Chain Reaction (PCR) in real time (qPCR).

Toxicological reproductive study of Cassia occidentalis L. in female Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cassia occidentalis L. (Leguminosae) has long been used as natural medicine in rainforests and other tropical regions for the treatment of inflammation, fever, liver disorders, constipation, worms, fungal infections, ulcers, respiratory infections, snakebite and as a potent abortifacient. AIM OF THE STUDY: This study has investigated the effects of oral sub-acute administration of Cassia occidentalis during pregnancy in female Wistar rats. MATERIALS AND METHODS: Three groups of pregnant rats were treated orally from the 1st to the 6th day (pre-implantation period) and from the 7th to the 14th day (organogenic period) of pregnancy, with doses of 250 and 500 mg/kg. On the 20th day of pregnancy, the animals were euthanized and reproductive parameters evaluated. RESULTS: The results revealed no statistically significant differences between the control and treated groups in terms of offspring/dam relationship; fetuses, placentae and ovaries weights; number of implantation and resorption sites; number of corpora lutea in the ovaries and pre- and post-implantation loss rates. However, the presence of dead fetuses was registered in both doses of 250 and 500 mg/kg of Cassia occidentalis. CONCLUSIONS: Further studies should therefore be conducted to obtain more detailed characteristics of the toxic effects of this species, the use of which is not recommended during pregnancy.

Fatty acid synthase expression in squamous cell carcinoma of the tongue: clinicopathological findings.

BACKGROUND: Overexpression of fatty acid synthase (FAS), the cytosolic enzyme responsible for the conversion of dietary carbohydrates to fatty acids, has been reported in several human malignancies and pointed as a potential prognostic marker for some tumors. This study investigated whether FAS immunohistochemical expression is correlated with the clinicopathological characteristics of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The clinical features of 102 patients with OSCC of the tongue treated in a single institution were obtained from the medical records and all histopathological diagnoses were reviewed. The expression of FAS was determined by the standard immunoperoxidase technique in formalin-fixed and paraffin-embedded specimens and correlated with the clinicopathological characteristics of the tumors. RESULTS: Eighty-one cases (79.41%) were positive for FAS. Microscopic characteristics such as histological grade (P < 0.05), lymphatic permeation (P < 0.001), perineural infiltration (P < 0.05), and nodal metastasis (P < 0.02) were associated with FAS status. A significantly lower survival probability for patients with advanced clinical stage (log-rank test, P < 0.001), lymph nodes metastasis (log-rank test, P < 0.001), presence of vascular permeation (log-rank test, P = 0.05), and perineural invasion (log-rank test, P = 0.01) was observed in the studied samples. CONCLUSION: The expression of FAS in OSCC of the tongue is associated with the microscopic characteristics that determine disease progression and prognosis.

Proliferation of fibroblasts cultured from normal gingiva and hereditary gingival fibromatosis is dependent on fatty acid synthase activity.

BACKGROUND: Fatty acid synthase (FAS) is the enzyme that synthesizes palmitate from malonyl-CoA and acetyl-CoA. Recent studies have shown that FAS is overexpressed in human cancers and that its activity is necessary for cell proliferation. Hereditary gingival fibromatosis (HGF) is a genetic disease manifested as a progressive enlargement of the gingiva. The pathogenesis of this condition is not understood; however, a proliferative advantage of HGF fibroblasts in comparison with cells from normal gingiva (NG) has been described. The aim of this study was to investigate the role of FAS in NG and HGF fibroblast proliferation. METHODS: NG and HGF fibroblasts had their proliferative potential assessed by automated cell counting and immunocytochemistry against Ki-67 or proliferating cell nuclear antigen (PCNA). The production of FAS, androgen receptor (AR), and ErbB2 was analyzed by Western blot and the pattern of FAS expression studied by immunocytochemistry. FAS activity was blocked by the specific inhibitor cerulenin. RESULTS: Higher proliferation rates were found in fibroblasts isolated from HGF than from NG. HGF fibroblasts with greater proliferative potential produced more FAS and AR than the cell lines with lower growth rates, and all studied cell lines produced similar amounts of the ErbB2 protein. In addition, the FAS inhibitor cerulenin was able to significantly reduce the proliferation of both NG and HGF cells. CONCLUSIONS: These results show that FAS is expressed by gingival fibroblasts and that highly proliferative HGF cells produced more FAS and AR than the other fibroblast cell lines. Moreover, FAS inhibition significantly reduced both NG and HGF fibroblast growth, suggesting a role for the androgen-driven fatty acid biosynthesis in their proliferation.