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Patient delay for potentially malignant oral symptoms.  


The detection of oral cancer at an early stage is the most effective means to improve survival and reduce morbidity, disfigurement, duration of treatment, and hospital costs associated with this disease. However, approximately 30% of patients delay seeking help for more than 3 months following the self-discovery of symptoms of oral cancer. This study aimed to increase our understanding of patient delay for potentially malignant oral symptoms in order to inform the development of interventions to encourage early presentation of oral cancer. Newly referred patients (n = 80) with potentially malignant oral symptoms completed a questionnaire to determine influences on the timing of their decision to seek help. Logistic regression analyses were conducted to determine factors associated with patient delay. The analysis indicated that the gravity of patients' initial symptom interpretation, the level of deprivation, knowledge of oral cancer, severity of life events in the patient delay period, and perceived ability to seek help for oral symptoms were significantly related to the duration of patient delay, with the latter three variables being independent predictors. The results are discussed with reference to their implications for interventions aimed at reducing patient delay for symptoms of oral cancer. PMID:18353007

Scott, Suzanne; McGurk, Mark; Grunfeld, Elizabeth



Advances in Optical Adjunctive Aids for Visualisation and Detection of Oral Malignant and Potentially Malignant Lesions  

PubMed Central

Traditional methods of screening for oral potentially malignant disorders and oral malignancies involve a conventional oral examination with digital palpation. Evidence indicates that conventional examination is a poor discriminator of oral mucosal lesions. A number of optical aids have been developed to assist the clinician to detect oral mucosal abnormalities and to differentiate benign lesions from sinister pathology. This paper discusses advances in optical technologies designed for the detection of oral mucosal abnormalities. The literature regarding such devices, VELscope and Identafi, is critically analysed, and the novel use of Narrow Band Imaging within the oral cavity is also discussed. Optical aids are effective in assisting with the detection of oral mucosal abnormalities; however, further research is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant and malignant lesions.

Bhatia, Nirav; Lalla, Yastira; Vu, An N.; Farah, Camile S.



[Detection of potentially malignant and malignant lesions of oral cavity using autofluorescence visualization device].  


Light-based oral cancer screening aids have been developed in identifying potentially malignant and malignant lesions of oral cavity at their earliest stage. The VELscope system is a simple hand-held device that facilitates the direct visualization of oral-cavity fluorescence for the detection of precancerous and cancerous lesions. Some published reports have shown that this system can assist in the detection of precancerous and cancerous lesions, but there is no evidence that it can distinguish between them. We studied whether objective discrimination criteria can be set for this system when observing oral mucosal lesions. We examined 74 cases with biopsy-confirmed oral mucosal lesions; 37 squamous cell carcinoma lesions, 14 moderate to severe epithelial dysplasia lesions, 13 mild epithelial dysplasia lesions and 10 lichen planus lesions. Lesions were examined macroscopically under the conventional overhead light, and then, examined by this device. Each examination was recorded with a digital camera. We contrasted findings with histopathological manifestation, and calculated the attenuation score. It is found that several conditions and sites, such as keratinization and the degree of inflammatory cell infiltration, were associated with detection sensitivity using this device. Based on the attenuation scores, a significant difference was seen between squamous cell carcinoma and epithelial dysplasia. It is suggested that this device might be a valuable adjunct in the early detection of potentially malignant and malignant lesions of the oral cavity. PMID:21827020

Matsumoto, Kanako



Detection of HPV16 genome in human oral cancers and potentially malignant lesions from India  

Microsoft Academic Search

The presence of high risk human papilloma virus (HPV) 16 and 18 was examined in 100 oral cancer patients of Indian descent, 80 patients with potentially malignant oral lesions and corresponding clinically normal mucosa from 48 of these patients. Additionally, presence of HPV-33, -6 and -11 was also studied in 86 oral cancers, 50 potentially malignant oral lesions and 30

Jenice D'Costa; Dhananjaya Saranath; Pratiksha Dedhia; Vikram Sanghvi; Ashok R Mehta



Is there any benefit in surgery for potentially malignant disorders of the oral cavity?  


Oral epithelial dysplasia grading is currently recognised as the most useful prognostic indicator for predicting conversion of potentially malignant disorders of the oral cavity to squamous cell carcinoma. It is also used as a basis for deciding management options. However, the diagnosis of oral epithelial dysplasia is subjective and thus unreliable. Surgery is currently recommended for removal of high-risk lesions; however, the evidence for its success is lacking, and in some cases, there have been reports of increased recurrence of malignancy following surgical excision. Molecular and genetic markers have been identified and show promising results in identifying which potential malignant disorders are at risk of malignant transformation. The current evidence available for prognosis of potential malignant disorders and its treatment is based on observational and retrospective data. No randomised control trials have been conducted to date to assess the efficacy of surgery in oral epithelial dysplasia. Until good quality evidence is available from well-designed randomised control trials, experts still recommend the surgical removal of potential malignant disorders which are regarded as high risk. PMID:23750566

Balasundaram, I; Payne, K F B; Al-Hadad, I; Alibhai, M; Thomas, S; Bhandari, R



CO2 lasers in the management of potentially malignant and malignant oral disorders  

PubMed Central

The CO2 laser was invented in 1963 by Kumar Patel. Since the early 1970s, CO2 laser has proved to be an effective method of treatment for patients with several types of oral lesions, including early squamous cell carcinoma. Laser surgery of oral premalignant disorders is an effective tool in a complete management strategy which includes careful clinical follow-up, patient education to eliminate risk factors, reporting and biopsying of suspicious lesions and any other significant lesions. However, in a number of patients, recurrence and progression to malignancy remains a risk. CO2 laser resection has become the preferred treatment for small oral and oropharyngeal carcinomas. Laser resection does not require reconstructive surgery. There is minimal scarring and thus, optimum functional results can be expected. New and improved applications of laser surgery in the treatment of oral and maxillofacial/head and neck disorders are being explored. As more surgeons become experienced in the use of lasers and as our knowledge of the capabilities and advantages of this tool expands, lasers may play a significant role in the management of different pathologies.



Aldehyde dehydrogenase 1 expression correlated with malignant potential of oral lichen planus.  


Oral lichen planus (OLP) is a potentially malignant disorder associated with an increased risk of oral squamous cell carcinoma (OSCC). The objective of this study was to determine protein expression of cancer stem cell marker aldehyde dehydrogenase 1 (ALDH1) in a series of patients with OLP and evaluate the correlation between ALDH1 expression and the risk of progression to OSCC. In a retrospective study, ALDH1 expression was determined using immunohistochemistry in samples from 101 patients with OLP who received a mean follow-up of 5 years, including 89 patients with untransformed OLP that did not develop into OSCC and 12 patients with malignant transformed OLP that had developed into OSCC. Analysis of 10 cases of normal oral mucosa and 6 cases of postmalignant OSCC form previously diagnosed OLP was also performed. The results showed that ALDH1 expression was observed in 27 (30.3%) of 89 cases of untransformed OLP and in 8 (66.7%) of 12 cases of transformed OLP (P = .021). Aldehyde dehydrogenase 1 was not expressed in normal oral mucosa, but it overexpressed in the 6 cases (100%) of OSCC. Multivariate analysis revealed that ALDH1 expression was significantly associated with a 6.71-fold (95% confidence interval, 1.64-27.42; P = .008) increased risk of malignant transformation. Collectively, ALDH1 expression was significantly associated with malignant transformation in a large series of patients with OLP. Our findings suggested that ALDH1 expression may identify a subgroup of a higher risk of malignant transformation of OLP. PMID:23707659

Xu, Ziyuan; Shen, Zhengyu; Shi, Linjun; Sun, Hongying; Liu, Wei; Zhou, Zengtong



Assessment of malignant potential of oral submucous fibrosis through evaluation of p63, E-cadherin and CD105 expression  

Microsoft Academic Search

BackgroundThe assessment of malignant potential of oral submucous fibrosis grades vis-à-vis their progression towards malignancy is associated with expression of possible multiple molecular markers.AimsTo analyse p63, E-cadherin and CD105 expression in this premalignant pathosis with a view to unravel and understand the expression of these molecules as markers.MethodsThe oral mucosal biopsies (normal, oral submucous fibrosis with and without dysplasia) were

Raunak Kumar Das; Mousumi Pal; Ananya Barui; Ranjan Rashmi Paul; Chandan Chakraborty; Ajoy Kumar Ray; Sanghamitra Sengupta; Jyotirmoy Chatterjee



Clinico-epidemiological profile of oral potentially malignant and malignant conditions among areca nut, tobacco and alcohol users in Eastern India: A hospital based study  

PubMed Central

Context: With an increase in the abuse of various oral habitual products in India over the past few decades; the incidence of oral potentially malignant conditions as leukoplakia, oral submucous fibrosis and squamous cell carcinoma (SCC) rates have also increased. No recent study has been conducted reporting the scenario of oral cancer and potentially malignant conditions in Eastern India (specifically Kolkata). Aims: The present study was conducted at Dr. R. Ahmed Dental College, Kolkata during 2010-2011 to find a possible correlation between the effects of the different oral habits, age, sex and the different types of oral mucosal lesions among patients reported to the hospital. This study also enabled us to see the predilection of the various histopathological stages of the lesions for different sites of the oral cavity. Subjects and Methods: The study group consisted of 698 patients having either oral potentially malignant or malignant lesion. The control group consisted of 948 patients who had reported to the hospital for different oral/dental problems and had the habit of tobacco, areca nut and/or alcohol usage for at least 1 year. Statistical Analysis: The unadjusted odds ratio, the 95% confidence interval, and the P value were calculated to correlate patients with/without different kinds of habit and having/not having various kinds of oral lesions. Results: Our study shows that for males having the habit of taking smokeless tobacco or mixed habit poses the highest risk for developing SCC. For females, significant risk of developing SCC was found in patients habituated to processed areca nut chewing. Conclusion: This study presents probably for the first time in recent years the occurrence of oral potentially malignant and malignant conditions amongst patients having deleterious habits in a hospital based population of Kolkata.

Ray, Jay Gopal; Ganguly, Madhurima; Rao, BH Sripathi; Mukherjee, Sanjit; Mahato, Basudev; Chaudhuri, Keya



Longitudinal evaluation of patients with oral potentially malignant disorders using optical imaging and spectroscopy  

NASA Astrophysics Data System (ADS)

Dysplastic and cancerous alterations in oral tissue can be detected noninvasively in vivo using optical techniques including autofluorescence imaging, high-resolution imaging, and spectroscopy. Interim results are presented from a longitudinal study in which optical imaging and spectroscopy were used to evaluate the progression of lesions over time in patients at high risk for development of oral cancer. Over 100 patients with oral potentially malignant disorders have been enrolled in the study to date. Areas of concern in the oral cavity are measured using widefield autofluorescence imaging and depth-sensitive optical spectroscopy during successive clinical visits. Autofluorescence intensity patterns and autofluorescence spectra are tracked over time and correlated with clinical observations. Patients whose lesions progress and who undergo surgery are also measured in the operating room immediately prior to surgery using autofluorescence imaging and spectroscopy, with the addition of intraoperative high-resolution imaging to characterize nuclear size, nuclear crowding, and tissue architecture at selected sites. Optical measurements are compared to histopathology results from biopsies and surgical specimens collected from the measured sites. Autofluorescence imaging and spectroscopy measurements are continued during post-surgery followup visits. We examined correlations between clinical impression and optical classification over time with an average followup period of 4 months. The data collected to date suggest that multimodal optical techniques may aid in noninvasive monitoring of the progression of oral premalignant lesions, biopsy site selection, and accurate delineation of lesion extent during surgery.

Schwarz, Richard A.; Pierce, Mark C.; Mondrik, Sharon; Gao, Wen; Quinn, Mary K.; Bhattar, Vijayashree; Williams, Michelle D.; Vigneswaran, Nadarajah; Gillenwater, Ann M.; Richards-Kortum, Rebecca



Photodynamic therapy: a review and its prospective role in the management of oral potentially malignant disorders.  


With the unreliability of epithelial dysplasia as a predictor to determine the risk of future malignant development, subjectivity associated in evaluating dysplasia by pathologists and paucity of biomarkers that could accurately predict the progression risks in oral potentially malignant disorders (PMDs), eradication of the lesions appears to be the most desirable approach to minimize the risk of invasive cancer formation. Interventions, such as surgery and chemoprevention, have not shown promising long-term results in the treatment of these lesions, and lack of guidelines and general consensus on their management has incited much anxiety and doubts in both patients and community clinicians. Topical photodynamic therapy (PDT) is a minimally invasive and minimally toxic technique that in recent years has shown great promise in the management of PMDs. In this review, we describe the historical developments in the field of PDT, its basic mechanisms, as well as related clinical studies, and its challenges in the management of oral PMDs. Based on its high efficacy and low side effects, its high patient acceptance/compliance, the simplicity of the procedure and its minimal pretreatment preparation, topical PDT is believed to have potential to play an important role in the management of PMDs, especially of the low-grade dysplasia. PMID:24079944

Saini, R; Poh, Cf



Evaluation of an autofluorescence based imaging system (VELscope™) in the detection of oral potentially malignant disorders and benign keratoses.  


Early detection of oral cancer is crucial in improving survival rate. Identification and detection of oral potentially malignant disorders (OPMD) allow delivery of interventions to reduce the evolution of these disorders to malignancy. A variety of new and emerging diagnostic aids and adjunctive techniques are currently available to potentially assist in the detection of OPMD. The objective of the present study was to evaluate the accuracy of autofluorescence against conventional oral examination and surgical biopsy. A total of 126 patients, 70 males and 56 females (mean age 58.5±11.9 years) who presented to the Oral Medicine Clinics at King's and Guy's Hospitals, London with oral white and red patches suspicious of OPMD were enrolled. Following a complete visual and autofluorescence examination, all underwent an incisional biopsy for histopathological assessment. Seventy patients had oral leukoplakia/erythroplakia, 32 had oral lichen planus, 9 chronic hyperplastic candidiasis and rest frictional keratosis (13) or oral submucous fibrosis (2). Of 126 lesions, 105 (83%) showed loss of fluorescence. Following biopsy 44 had oral epithelial dysplasia (29 mild, 8 moderate and 7 severe). The sensitivity (se) and specificity (sp) of autofluorescence for the detection of a dysplastic lesion was 84.1% and 15.3% respectively. While VELscope was useful in confirming the presence of oral leukoplakia and erythroplakia and other oral mucosal disorders, the device was unable to discriminate high-risk from low-risk lesions. PMID:21396880

Awan, K H; Morgan, P R; Warnakulasuriya, S



Smoking and drinking in relation to oral potentially malignant disorders in Puerto Rico: a case-control study  

PubMed Central

Background Oral cancer incidence is high on the Island of Puerto Rico (PR), particularly among males. As part of a larger study conducted in PR, we evaluated smoking and drinking as risk factors for oral potentially malignant disorders (OPMDs). Methods Persons diagnosed with either an OPMD (n = 86) [oral epithelial dysplasia (OED), oral hyperkeratosis/epithelial hyperplasia without OED] or a benign oral tissue condition (n = 155) were identified through PR pathology laboratories. Subjects were interviewed using a standardized, structured questionnaire that obtained information, including detailed histories of smoking and drinking. Odds ratios (ORs) for smoking and drinking in relation to having an OPMD, relative to persons with a benign oral tissue condition, were obtained using logistic regression and adjusted for age, gender, education, fruit/vegetable intake and smoking or drinking. Results For persons with an OPMD and relative to individuals with a benign oral tissue condition, the adjusted OR for current smoking was 4.32 (95% CI: 1.99-9.38), while for former smokers, the ORadj was 1.47 (95% CI: 0.67-3.21), each ORadj relative to never smokers. With regard to drinking, no adjusted ORs approached statistical significance, and few point estimates exceeded 1.0, whether consumption was defined in terms of ever, current, level (drinks/week), or beverage type. Conclusions In this study, conducted in Puerto Rico, current smoking was a substantial risk factor for OPMDs while former smokers had a considerably reduced risk compared to current smokers. There was little evidence suggesting that alcohol consumption was positively associated with OPMD risk.



Prevalence of oral cancer and potentially malignant lesions among shammah users in Yemen.  


The purpose of this study was to assess the prevalence of oral precancerous lesions and squamous cell carcinoma (OSCC) in Yemeni users of shammah, a traditional smokeless tobacco habit known in the Arabian Peninsula. The study group comprised 199 male and one female shammah users who were interviewed via a standardised questionnaire and clinically examined in 48 Yemeni villages and cities. Cases with oral leukoplakia (OL) or mucosal burns (MB) were compared with users without any lesion. MB were detected in 31%, of which 46.8% were located on the tongue or floor of the mouth, and OL in 27%, of which 59.2% were located in the same region. In addition, two cases (1%) of apparent OSCC were identified. Statistically significant increased OR (95% CI) of OL were (a) 6.91 (2.66-17.95) for an average duration of the respective shammah application >5min.; (b) 4.90 (1.99-12.08) for a daily frequency of those applications >10; and (c) 4.22 (1.43-12.43) for a daily duration >6h of chewing qat, also a traditional habit in Yemen. Likewise, decreased OR were (a) 0.39 (0.18-0.85) for rinsing the mouth after the shammah application; (b) 0.36 (0.17-0.78) for successful attempts to stop the use in the past; and (c) 0.26 (0.09-0.72) for existing knowledge about the carcinogenicity of shammah that was present in only 19% overall. In conclusion, evidence was shown for a significant association between the prevalence of OL and the daily duration of shammah application in a dose-dependent manner. An appropriate public health program might help to reduce this potential OSCC burden in shammah users. PMID:16759897

Scheifele, C; Nassar, A; Reichart, P A



Computer vision approach to morphometric feature analysis of basal cell nuclei for evaluating malignant potentiality of oral submucous fibrosis.  


This research work presents a quantitative approach for analysis of histomorphometric features of the basal cell nuclei in respect to their size, shape and intensity of staining, from surface epithelium of Oral Submucous Fibrosis showing dysplasia (OSFD) to that of the Normal Oral Mucosa (NOM). For all biological activity, the basal cells of the surface epithelium form the proliferative compartment and therefore their morphometric changes will spell the intricate biological behavior pertaining to normal cellular functions as well as in premalignant and malignant status. In view of this, the changes in shape, size and intensity of staining of the nuclei in the basal cell layer of the NOM and OSFD have been studied. Geometric, Zernike moments and Fourier descriptor (FD) based as well as intensity based features are extracted for histomorphometric pattern analysis of the nuclei. All these features are statistically analyzed along with 3D visualization in order to discriminate the groups. Results showed increase in the dimensions (area and perimeter), shape parameters and decreasing mean nuclei intensity of the nuclei in OSFD in respect to NOM. Further, the selected features are fed to the Bayesian classifier to discriminate normal and OSFD. The morphometric and intensity features provide a good sensitivity of 100%, specificity of 98.53% and positive predicative accuracy of 97.35%. This comparative quantitative characterization of basal cell nuclei will be of immense help for oral onco-pathologists, researchers and clinicians to assess the biological behavior of OSFD, specially relating to their premalignant and malignant potentiality. As a future direction more extensive study involving more number of disease subjects is observed. PMID:21152957

Muthu Rama Krishnan, M; Pal, Mousumi; Paul, Ranjan Rashmi; Chakraborty, Chandan; Chatterjee, Jyotirmoy; Ray, Ajoy K



Molecular and phenotypic expression of decorin as modulator of angiogenesis in human potentially malignant oral lesions and oral squamous cell carcinomas.  


Background: Decorin is an extracellular matrix, multifunctional small proteoglycan molecule in tumor stroma that has been shown to be modulator of angiogenesis. No clinical data is available so far on decorin expression and survival outcome of oral cancer. Aim: The aim of the present study was to examine molecular and phenotypic expression of two angiogenesis modulators viz. decorin and vascular endothelial growth factor-A (VEGF-A) in human potentially malignant oral lesions (PMOLs) and oral squamous cell carcinomas (OSCC) in relation to clinico-pathological variables and survival outcome. Materials and Methods: Tissue biopsies were obtained from 72 PMOLs, 108 OSCC and 52 healthy controls. The PMOLs included cases of leukoplakias and oral submucous fibrosis. Immunohistochemistry was performed using antibodies against decorin, VEGF-A and CD-31. Messenger-ribonucleic acid (mRNA) expression was analyzed by using real-time polymerase chain reaction. Results: Cytoplasmic staining of decorin was observed in the basal layer of epithelium in 53 (73.61%) cases of PMOLs and in peritumoral stroma in 55 (50.92%) cases of OSCC. None of the cases showed nuclear expression of decorin. Decorin expression both at phenotypic and molecular level was found to be down-regulated from PMOLs to OSCC. Lymph node metastasis and reduced decorin expression independently correlated with overall survival in OSCC. VEGF-A expression had no significant impact on survival outcome. Conclusion: Micro vessel density and VEGF-A expression were significantly associated with reduced decorin expression in tumor stroma suggesting, decorin as angiogenic modulator in OSCC. Down-regulation of decorin expression and the presence of lymph node metastasis were adverse factor independently affecting overall survival in OSCC. PMID:24152495

Nayak, Seema; Goel, Madhu Mati; Bhatia, Vikram; Chandra, Saumya; Makker, Annu; Kumar, Sandeep; Agrawal, Satya Prakash; Mehrotra, Divya; Rath, Srikanta Kumar


Malignancy Risk Models for Oral Lesions  

PubMed Central

Objectives: The aim of this work was to assess risk habits, clinical and cellular phenotypes and TP53 DNA changes in oral mucosa samples from patients with Oral Potentially Malignant Disorders (OPMD), in order to create models that enable genotypic and phenotypic patterns to be obtained that determine the risk of lesions becoming malignant. Study Design: Clinical phenotypes, family history of cancer and risk habits were collected in clinical histories. TP53 gene mutation and morphometric-morphological features were studied, and multivariate models were applied. Three groups were estabished: a) oral cancer (OC) group (n=10), b) OPMD group (n=10), and c) control group (n=8). Results: An average of 50% of patients with malignancy were found to have smoking and drinking habits. A high percentage of TP53 mutations were observed in OC (30%) and OPMD (average 20%) lesions (p=0.000). The majority of these mutations were GC ? TA transversion mutations (60%). However, patients with OC presented mutations in all the exons and introns studied. Highest diagnostic accuracy (p=0.0001) was observed when incorporating alcohol and tobacco habits variables with TP53 mutations. Conclusions: Our results prove to be statistically reliable, with parameter estimates that are nearly unbiased even for small sample sizes. Models 2 and 3 were the most accurate for assessing the risk of an OPMD becoming cancerous. However, in a public health context, model 3 is the most recommended because the characteristics considered are easier and less costly to evaluate. Key words:TP53, oral potentially malignant disorders, risk factors, genotype, phenotype.

Zarate, Ana M.; Brezzo, Maria M.; Secchi, Dante G.; Barra, Jose L.



Inhibition of microflora associated with oral malignancy  

Microsoft Academic Search

Changes in the microflora on oral carcinoma surfaces may lead to both local and systemic infections, which may complicate the morbidity of the patient suffering from oral malignant neoplasms. Thus, anticancer therapy, irradiation, chemotherapy or surgery impairs the defence mechanism of the oral mucosa and is accompanied by proliferation of the mucosal biofilm with overgrowth of yeast and bacteria. This

K. Nagy; I. Szöke; I. Sonkodi; E. Nagy; A. Mari; G. Szolnoky; H. N. Newman



Derivation and validation of a risk-factor model for detection of oral potentially malignant disorders in populations with high prevalence  

PubMed Central

Background: Oral and pharyngeal cancers constitute the sixth most common type of cancer globally, with high morbidity and mortality. In many countries, most cases of oral cancer arise from long-standing, pre-existing lesions, yet advanced malignancies prevail. A new approach to early detection is needed. We aimed to validate a model for screening so that only high-risk individuals receive the clinical examination. Methods: A community-based case–control study (n=1029) in rural Sri Lanka assessed risk factors and markers for oral potentially malignant disorders (OPMD) by administering a questionnaire followed by an oral examination. We then developed a model based on age, socioeconomic status and habits of betel-quid chewing, alcohol drinking and tobacco smoking, with weightings based on odds ratios from the multiple logistic regression. A total, single score was calculated per individual. Standard receiver-operator characteristic curves were plotted for the total score and presence of OPMD. The model was validated on a new sample of 410 subjects in a different community. Results: A score of 12.0 produced optimal sensitivity (95.5%), specificity (75.9%), false-positive rate (24.0%), false-negative rate (4.5%), positive predictive value (35.9%) and negative predictive value (99.2%). Conclusion: This model is suitable for detection of OPMD and oral cancer in high-risk communities, for example, in Asia, the Pacific and the global diaspora therefrom. A combined risk-factor score of 12.0 was optimal for participation in oral cancer/OPMD screening in Sri Lanka. The model, or local adaptations, should have wide applicability.

Amarasinghe, H K; Johnson, N W; Lalloo, R; Kumaraarachchi, M; Warnakulasuriya, S



Tuberculosis masquerading as oral malignancy  

PubMed Central

Tuberculosis of the oral cavity is a rare condition. A 55-year-old labourer was referred as a case of oral cancer for further management. The patient had no systemic symptoms. Biopsy of the lesion revealed caseating granulomatous inflammation. Chest X-ray and sputum revealed evidence of asymptomatic pulmonary tuberculosis. The purpose of this paper is to sensitize clinicians to consider oral tuberculosis as a differential diagnosis in patients with an Non-healing oral cavity ulcer.

Kannan, S.; Thakkar, Purvi; Dcruz, Anil K.



Betel-quid chewing with or without tobacco is a major risk factor for oral potentially malignant disorders in Sri Lanka: a case-control study.  


We investigated the prevalence of, and risk factors for, oral potentially malignant disorders (OPMDs) in rural Sri Lanka. A cross-sectional community-based study was conducted by interview and oral examination of 1029 subjects aged over 30 years. A community-based nested case-control study then took those with OPMDs as 'cases', "controls" being those with no oral abnormalities at time of initial screening. The prevalence of OPMD was 11.3% (95% CI: 9.4-13.2), after weighting for place of residence and gender. Risk factors were betel-quid (BQ) chewing daily [OR=10.6 (95% CI: 3.6-31.0)] and alcohol drinking daily or weekly [OR=3.55 (1.6-8.0)]. A significant dose-response relationship existed for BQ chewing. Smoking did not emerge when adjusted for covariates. A synergistic effect of chewing and alcohol consumption existed. The attributable risk (AR) of daily BQ chewing was 90.6%, the population AR 84%. This study demonstrates high prevalence of OPMD, betel-quid chewing with or without tobacco being the major risk factor. PMID:20189448

Amarasinghe, Hemantha K; Usgodaarachchi, Udaya S; Johnson, Newell W; Lalloo, Ratilal; Warnakulasuriya, Saman



Oral Submucous Fibrosis, a Clinically Benign but Potentially Malignant Disease: Report of 3 Cases and Review of the Literature  

Microsoft Academic Search

Oral submucous fibrosis (OSF) is a premalignant condition mainly associated with the practice of chewing betel quid containing areca nut, a habit common among South Asian people. It is characterized by inflammation, increased deposition of submucosal collagen and formation of fibrotic bands in the oral and paraoral tissues, which increasingly limit mouth opening. Recently, OSF has been reported among South

Sumanth KN


Computer Vision Approach to Morphometric Feature Analysis of Basal Cell Nuclei for Evaluating Malignant Potentiality of Oral Submucous Fibrosis  

Microsoft Academic Search

This research work presents a quantitative approach for analysis of histomorphometric features of the basal cell nuclei in\\u000a respect to their size, shape and intensity of staining, from surface epithelium of Oral Submucous Fibrosis showing dysplasia\\u000a (OSFD) to that of the Normal Oral Mucosa (NOM). For all biological activity, the basal cells of the surface epithelium form\\u000a the proliferative compartment

M. Muthu Rama Krishnan; Mousumi Pal; Ranjan Rashmi Paul; Chandan Chakraborty; Jyotirmoy Chatterjee; Ajoy K. Ray


The clinical features, malignant potential, and systemic associations of oral lichen planus: A study of 723 patients  

Microsoft Academic Search

Background: Although oral lichen planus (OLP) is a relatively common disorder, reports comprising large numbers of patients with the disease are lacking in the dermatology literature. Objective and Methods: The purpose of this investigation was to describe the clinical characteristics of 723 patients with biopsy-proven OLP who were followed up from 6 months to 8 years (mean, 4.5 years). Results:

Drore Eisen



Oral submucous fibrosis, a clinically benign but potentially malignant disease: report of 3 cases and review of the literature.  


Oral submucous fibrosis (OSF) is a premalignant condition mainly associated with the practice of chewing betel quid containing areca nut, a habit common among South Asian people. It is characterized by inflammation, increased deposition of submucosal collagen and formation of fibrotic bands in the oral and paraoral tissues, which increasingly limit mouth opening. Recently, OSF has been reported among South Asian immigrants in Canada, the United Kingdom and Germany. Dentists in western countries should enhance their knowledge of this disease as it seems to be increasing with population migration. In this paper, we review the literature on OSF and present 3 cases representing different stages of the disease to help dentists make an early diagnosis and reduce the morbidity and mortality associated with this condition. PMID:18845065

Auluck, Ajit; Rosin, Miriam P; Zhang, Lewei; Sumanth, K N



Malignant transformation of oral lichen planus in lingual location: report of a case  

Microsoft Academic Search

One of the most controversial aspects of oral lichen planus (OLP) is its malignant potential. There have been a few well-documented reports of malignant transformation in the absence of known exposure to exogenous carcinogens. The aim of this study is to report the case of a patient with a lesion previously diagnosed as oral lichen planus, who developed squamous cell

José Manuel Gándara-Rey; Márcio Diniz Freitas; Pilar Gándara Vila; Andrés Blanco Carrión; José Manuel Suárez Peñaranda; Abel Garcia Garcia



Methylation-Mediated Molecular Dysregulation in Clinical Oral Malignancy  

PubMed Central

Herein we provide a concise review of the state of methylation research as it pertains to clinical oral cancerous and precancerous tissues. We provide context for ongoing research efforts in this field and describe technologies that are presently being applied to analyze clinical specimens. We also discuss the various recurrent methylation changes that have been reported for oral malignancy (including those genes frequently silenced by promoter methylation and the small RNAs with activity modulated by methylation changes) and describe surrogate disease markers identified via epigenetic analysis of saliva and blood specimens from patients with oral cancer.

Towle, Rebecca; Garnis, Cathie



Malignant transformation of oral leukoplakia in a well-defined cohort of 144 patients.  


OBJECTIVES: Oral leukoplakia is a potentially malignant disorder of the oral mucosa. The aim of this retrospective study was to identify the factors that possibly predict malignant transformation in a well-defined cohort of patients with a long-term follow-up. All leukoplakias were staged according to a clinicopathological classification and staging system. Furthermore, a certainty factor has been used with which the diagnosis has been established. MATERIAL AND METHODS: The group consisted of 144 patients. The size, presence and degree of epithelial dysplasia were incorporated into a clinicopathological classification and staging system. Initial management consisted of surgical excision, CO2 laser vaporisation or observation only. The mean follow-up period was 51.2 months (s.d. = 39.33, range 12-179 months). RESULTS: In 16 of 144 patients (11%), malignant transformation occurred between 20 and 94 months (mean 57.0 months) after the first visit, the annual malignant transformation rate being approximately 2.6%. A large size of the lesion (? 4 cm) showed to be the only statistically significant predictor of malignant transformation (P = 0.034). CONCLUSION: A size of ? 4 cm showed to be the only significant predicting factor of malignant transformation in oral leukoplakia. No other epidemiological, aetiological, clinical or histopathological parameters were of statistical significance. PMID:23521625

Brouns, Erea; Baart, Ja; Karagozoglu, Kh; Aartman, Iha; Bloemena, E; van der Waal, I



Detection of galectins during malignant transformation of oral cells  

PubMed Central

Oral cancer is a common neoplasm world-wide. The incidence and mortality have increased over the past decades. It is characterized by poor prognosis and a low survival rate despite sophisticated surgical and radiotherapeutic modalities. Galectins are detected in a wide variety of tissues. The expression of galectins is modulated during the differentiation of individual cells and during the development of organisms and tissues, being altered in different physiological or pathological conditions including, carcinogenesis. In this review, we will discuss the role of galectins during the malignant transformation of oral cells, in order to understand their mechanisms of the action in a several cellular activities and test systems. Certainly, such information will contribute for understanding oral cancer pathogenesis.

Hossaka, Thais A; Focchi, Gustavo R; Oshima, Celina T F; Ribeiro, Daniel A



Adrenal oncocytic neoplasm with uncertain malignant potential.  


Adrenal oncocytic neoplasms (AONs) are a rare group of tumours with a somewhat uncertain natural history and clinical behaviour. Out of 46 cases of AON reported to date, 6 cases were histologically classified as neoplasms with uncertain malignant potential. We report the case of a 35-year-old male with an incidentally-detected large AON with mostly benign morphology and some characteristics which would make its behaviour uncertain. PMID:23862048

Ahmed, Mooyad A; Sureshkannan, K S; Raouf, Zaid R; Koliyadan, Sreedharan V; Grant, Christopher S; Al-Habsi, Ahmed H; Saparamadu, P A M; Al-Sajee, Dhuha



Diagnosis and management of mucosal lesions with the potential for malignant transformation.  


Squamous cell carcinoma is the most common oral cancer of the head and neck region. Up to 50 percent of these cancers have spread by the time of diagnosis; therefore, early diagnosis is vital. Oral lichen planus and epithelial dysplasia are two of the most common types of oral lesions with the potential for malignant transformation. The epidemiology and management of these conditions are discussed in this review. PMID:23795519

Issa, Bassam; Padilla, Ricardo; Brennan, Michael T



Evaluation of PTEN immunoexpression in oral submucous fibrosis: role in pathogenesis and malignant transformation.  


Oral submucous fibrosis (OSMF) is a chronic debilitating disease and a premalignant condition of the oral cavity characterized by generalized submucosal fibrosis. Despite its precancerous nature, the molecular biology regarding its malignant potential has not been extensively studied. PTEN, a known tumor suppressor gene is mutated in a majority of human cancers and has also been implicated in several fibrotic disorders. The present study aims to evaluate the expression of PTEN in OSMF and oral squamous cell carcinoma (OSCC) and correlate it with the pathogenesis and malignant transformation of OSMF. 60 cases total of OSMF (30) and OSCC (30) were subjected to immunohistochemistry using PTEN antibody. Ten normal oral mucosa (NOM) specimens were also stained as controls. There was progressive loss of PTEN expression from normal mucosa to OSMF and OSCC (p ? 0.001). Significant differences were observed for PTEN expression between NOM and OSMF, OSMF and OSCC as well as NOM and OSCC. Though a progressive loss of PTEN was noticed between early OSMF and advanced OSMF, the variation did not reach statistical significance (p ? 0.001). Data suggest that there is a significant loss of PTEN expression in OSMF as compared to normal oral mucosa and that this trend increased from OSMF to OSCC. Thus, alteration of PTEN is likely an important molecular event in OSMF pathogenesis and oral carcinogenesis. PMID:22392409

Angadi, Punnya V; Krishnapillai, Rekha



Diagnostic accuracy of diffuse reflectance imaging for early detection of pre-malignant and malignant changes in the oral cavity: a feasibility study.  


BACKGROUND: Diffusely reflected light is influenced by cytologic and morphologic changes that take place during tissue transformation, such as, nuclear changes, extracellular matrix structure and composition as well as blood flow. Albeit with varying degree of sensitivity and specificity, the properties of diffusely reflected light in discriminating a variety of oral lesions have been demonstrated by our group in multiple studies using point monitoring systems. However, the point monitoring system could not identify the region with the most malignant potential in a single sitting. METHODS: In order to scan the entire lesion, we developed a multi-spectral imaging camera system that records diffuse reflectance (DR) images of the oral lesion at 545 and 575 nm with white light illumination. The diagnostic accuracy of the system for 2-dimensional DR imaging of pre-malignant and malignant changes in the oral cavity was evaluated through a clinical study in 55 patients and 23 healthy volunteers. The DR imaging data were compared with gold standard tissue biopsy and histopathology results. RESULTS: In total 106- normal/clinically healthy sites, 20- pre-malignant and 29- malignant (SCC) sites were compared. While the median pixel value of the R545/R575 image ratio for normal/clinically healthy tissue was 0.87 (IQR = 0.82-0.94), they were 1.35 (IQR = 1.13-1.67) and 2.44 (IQR = 1.78-3.80) for pre-malignant and malignant lesions, respectively. Area under the ROC curve to differentiate malignant from normal/clinically healthy [AUC = 0.99 (95% CI: 0.99-1.00)], pre-malignant from normal/clinically healthy [AUC = 0.94 (95% CI: 0.86-1.00)], malignant from pre-malignant [AUC = 0.84 (95% CI: 0.73-0.95)] and pre-malignant and malignant from normal/clinically healthy [AUC = 0.97 (95% CI: 0.94-1.00)] lesions were desirable. CONCLUSION: We find DR imaging to be very effective as a screening tool in locating the potentially malignant areas of oral lesions with relatively good diagnostic accuracy while comparing it to the gold standard histopathology. PMID:23738507

Stephen, Manju M; Jayanthi, Jayaraj L; Unni, Nisha G; Kolady, Philip E; Beena, Valappil T; Jeemon, Panniyammakal; Subhash, Narayanan



Quantitative Proteomics Reveals Myosin and Actin as Promising Saliva Biomarkers for Distinguishing Pre-Malignant and Malignant Oral Lesions  

PubMed Central

Background Oral cancer survival rates increase significantly when it is detected and treated early. Unfortunately, clinicians now lack tests which easily and reliably distinguish pre-malignant oral lesions from those already transitioned to malignancy. A test for proteins, ones found in non-invasively-collected whole saliva and whose abundances distinguish these lesion types, would meet this critical need. Methodology/Principal Findings To discover such proteins, in a first-of-its-kind study we used advanced mass spectrometry-based quantitative proteomics analysis of the pooled soluble fraction of whole saliva from four subjects with pre-malignant lesions and four with malignant lesions. We prioritized candidate biomarkers via bioinformatics and validated selected proteins by western blotting. Bioinformatic analysis of differentially abundant proteins and initial western blotting revealed increased abundance of myosin and actin in patients with malignant lesions. We validated those results by additional western blotting of individual whole saliva samples from twelve other subjects with pre-malignant oral lesions and twelve with malignant oral lesions. Sensitivity/specificity values for distinguishing between different lesion types were 100%/75% (p?=?0.002) for actin, and 67%/83% (p<0.00001) for myosin in soluble saliva. Exfoliated epithelial cells from subjects' saliva also showed increased myosin and actin abundance in those with malignant lesions, linking our observations in soluble saliva to abundance differences between pre-malignant and malignant cells. Conclusions/Significance Salivary actin and myosin abundances distinguish oral lesion types with sensitivity and specificity rivaling other non-invasive oral cancer tests. Our findings provide a promising starting point for the development of non-invasive and inexpensive salivary tests to reliably detect oral cancer early.

Onsongo, Getiria; Stone, Matthew D.; Chen, Xiao-Bing; Kooren, Joel A.; Refsland, Eric W.; Griffin, Robert J.; Ondrey, Frank G.; Wu, Baolin; Le, Chap T.; Rhodus, Nelson L.; Carlis, John V.; Griffin, Timothy J.



Primary Oral Malignant Melanoma: Two Case Reports and Review of Literature  

PubMed Central

Primary malignant melanoma of the oral cavity is a rare neoplasm. The tumors tend to metastasize or locally invade tissue more readily than other malignant tumors in the oral region. The survival of patients with mucosal melanomas is less than for those with cutaneous melanomas. Tumor size and metastases are related to the prognosis of the disease. Early detection, therefore, is important.

Sharma, Neeraj



In Vitro Studies on Erythrosine-Based Photodynamic Therapy of Malignant and Pre-Malignant Oral Epithelial Cells  

PubMed Central

Photodynamic Therapy (PDT) involves the administration of a tumor localizing photosensitizing agent, which upon activation with light of an appropriate wavelength leads to the destruction of the tumor cells. The aim of the present study was to determine the efficacy of erythrosine as a photosensitizer for the PDT of oral malignancies. The drug uptake kinetics of erythrosine in malignant (H357) and pre-malignant (DOK) oral epithelial cells and their susceptibility to erythrosine-based PDT was studied along with the determination of the subcellular localization of erythrosine. This was followed by initial investigations into the mechanism of cell killing induced following PDT involving both high and low concentrations of erythrosine. The results showed that at 37°C the uptake of erythrosine by both DOK and H357 cells increased in an erythrosine dose dependent manner. However, the percentage of cell killing observed following PDT differed between the 2 cell lines; a maximum of ?80% of DOK cell killing was achieved as compared to ?60% killing for H357 cells. Both the DOK and H357 cell types exhibited predominantly mitochondrial accumulation of erythrosine, but the mitochondrial trans-membrane potential (??m) studies showed that the H357 cells were far more resistant to the changes in ??m when compared to the DOK cells and this might be a factor in the apparent relative resistance of the H357 cells to PDT. Finally, cell death morphology and caspase activity analysis studies demonstrated the occurrence of extensive necrosis with high dose PDT in DOK cells, whereas apoptosis was observed at lower doses of PDT for both cell lines. For H357 cells, high dose PDT produced both apoptotic as well as necrotic responses. This is the first instance of erythrosine-based PDT's usage for cancer cell killing.

Garg, Abhishek D.; Bose, Muthiah; Ahmed, Mohammed I.; Bonass, William A.; Wood, Simon R.



Primary malignant melanoma of the oral cavity: a case report.  


A 43-year-old white man was referred to the Special Care Dentistry Center of the School of Dentistry, University of Sao Paulo, Brazil, for the diagnosis of an extensive nodular lesion of the maxillary gingiva. The patient complained that his left maxilla had swollen over the last 4 months, with some exudation from the gingival crevice, sporadic bleeding, and slight tooth mobility, but no pain. An extra-oral examination confirmed expressive swelling of the left side of the face (Fig. 1A). Palpation disclosed bilateral enlargement of the submandibular lymph nodes. An intra-oral examination showed an extensive, reddish, nodular mass (around 11 cm in diameter) that extended from the last left maxillary molar to the right maxillary incisor, covered by a mucosa that was ulcerated in some areas (Fig. 1B,C). Palpation revealed a painless, soft, bleeding tissue that seemed to arise in the periodontal ligaments, extending to the palate and vestibular area. A small pigmented spot was found in the palatal mass. Histopathologically, the biopsy revealed a proliferation of neoplastic cells that exhibited a wide variety of shapes, including spindle, plasmacytoid, and epithelioid forms. The atypical cells showed enlarged and pleomorphic nuclei. Mitotic activity and pigmented areas were observed (Fig. 2A,B). Immunohistochemistry was used to establish the final diagnosis. The tumor cells strongly expressed S100 protein, gp100 (HMB-45), melan A, and tyrosine antibodies (Fig. 2C,D). With the diagnosis of malignant melanoma, the patient was referred to an oncologist for treatment. As computed tomography revealed that the lesion was deeply inserted into the skull surface (Fig. 1D), surgical intervention was not possible. The patient underwent radiotherapy, but died 14 months later. PMID:15485534

López Ortega, Karem; Soares de Araújo, Ney; Bitu de Souza, Fabricio; Magalhães, Marina H C G



Keratin profiles of normal and malignant oral mucosa using exfoliative cytology.  

PubMed Central

AIMS--To assess keratin profiles from smears of malignant and contralateral normal oral mucosa as part of the development of a screening procedure for oral cancer based on exfoliative cytology. METHODS--Smears were taken from oral cancers (confirmed by biopsy) and from the contralateral site of 20 patients. Using a panel of antikeratin antibodies, the keratins expressed by these cells were identified using a standard immunocytochemical technique (Vectastain) and assessed on a 3 point scale. RESULTS--Using chi 2 analysis, noticeable differences between the keratin profiles for malignant mucosal smears compared with the contralateral mucosal smears were found. This was particularly evident for the simple epithelial keratins. CONCLUSION--Individual keratins can be identified in smears from oral cancers. The identification of simple epithelial keratins seem to be the best keratin markers associated with malignancy. Their detection within smears from oral lesions could be valuable in the early diagnosis of oral cancer. Images

Ogden, G R; McQueen, S; Chisholm, D M; Lane, E B



Benign and Malignant Melanocytic Lesions of The Oral Mucosa. An Analysis Of 135 Cases.  

National Technical Information Service (NTIS)

All cases of melanocytic lesions of the oral mucosa, benign and malignant, accessioned by the AFIP during a 28-year period have been reviewed. There were 135 acceptable cases, 93 of which were benign and 42 malignant. A majority of the benign lesions occu...

J. N. Trodahl W. G. Sprague



Urachal mucinous tumor of uncertain malignant potential: a case report.  


Urachal mucinous tumor of uncertain malignant potential is very rare and is characterized by a multilocular cyst showing the proliferation of atypical mucin-secreting cells without stromal invasion. As in ovarian and appendiceal borderline tumors, it represents a transitional stage of mucinous carcinogenesis in the urachus. In addition, this tumor may recur locally and develop into pseudomyxoma peritonei. Due to its scarcity and diagnostic challenges, we report a mucinous tumor of uncertain malignant potential arising in the urachus. PMID:23109984

Choi, Jung-Woo; Lee, Ju-Han; Kim, Young-Sik



Urachal Mucinous Tumor of Uncertain Malignant Potential: A Case Report  

PubMed Central

Urachal mucinous tumor of uncertain malignant potential is very rare and is characterized by a multilocular cyst showing the proliferation of atypical mucin-secreting cells without stromal invasion. As in ovarian and appendiceal borderline tumors, it represents a transitional stage of mucinous carcinogenesis in the urachus. In addition, this tumor may recur locally and develop into pseudomyxoma peritonei. Due to its scarcity and diagnostic challenges, we report a mucinous tumor of uncertain malignant potential arising in the urachus.

Choi, Jung-Woo; Lee, Ju-Han



Dental practitioner's knowledge, opinions and methods of management of oral premalignancy and malignancy  

PubMed Central

Objectives The present study outlines the results of a pilot study to determine the knowledge and awareness of a cohort of dentists in United Arab Emirates (UAE) regarding aetiology, clinical features and appropriate early management of oral premalignant and malignant lesions. Materials and methods A self-administered questionnaire was constructed and posted to 300 UAE Dental Practitoners (DPs), selected randomly from the register of Emirates Dental Association. The present report details the responses of this cohort. Results 182 questionnaires were completed and returned (response rate 60.6%). One hundred and twenty-seven (69.8%) of the responding dentists were male and the median age of the DPs was 40 years (range 24–75 years). The majority (84%) practised or had practised in or around Dubai and Sharjah, 75% had graduated from a dental school after 1980. Eighty-two respondents (45.0%) had attended specific courses on premalignant or malignant oral lesions. During their undergraduate training 70% of DPs had witnessed more than 10 patients with oral SCC. Only 60.4% of respondents indicated that the tobacco and alcohol use were the principle causes of oral SCC while 19.7% suggested that HIV disease was a risk factor for oral SCC. 29% of DPs routinely recorded the tobacco or alcohol use of their patients and only 3.8% offered advice to patients regarding modification of these habits. Eight-three percent of the respondents suggested that clinical screening was an effective means of reducing the frequency of premalignant and malignant oral lesions. Conclusions In view of the gradual rise in oral malignancy worldwide there is an increased need for DPs to be able to recognize the signs and symptoms of oral malignancy and premalignancy, provide appropriate preventive advice and be aware of the appropriate early management of patients with such oral lesions.

Abdullah Jaber, Mohamed



Potential Oral Health Benefits of Cranberry  

Microsoft Academic Search

In the past decade, cranberry extracts have been attracting ever-growing attention by dental researchers. The potential benefits of cranberry components in reducing oral diseases, including dental caries and periodontitis, are discussed in this review. A non-dialysable cranberry fraction enriched in high molecular weight polyphenols has very promising properties with respect to cariogenic and periodontopathogenic bacteria, as well as to the

C. Bodet; D. Grenier; F. Chandad; I. Ofek; D. Steinberg; E. I. Weiss



Ex vivo photodynamic diagnosis to detect malignant cells in oral brush biopsies  

Microsoft Academic Search

In this study we proved the efficiency of the fluorimetric detection of a minimum number of malignant cells ex vivo. The goal\\u000a of this work was to investigate whether the combination of photodynamic diagnosis (PDD) with oral brush biopsy might become\\u000a a suitable chair-side tool to detect early oral carcinoma. Small numbers (100–500) of established human tumour cells—small\\u000a cell lung carcinoma

Laila Omar Hamad; Anja Vervoorts; Thomas Hennig; Rainer Bayer



Oral health and quality of life among patients with head and neck cancer or haematological malignancies  

Microsoft Academic Search

The aim of the present study was to monitor the health-related quality of life (HRQOL) of patients with head and neck cancer or haematological malignancies during a period from before to after medical treatment, and to investigate the relationships between patient experiences of oral symptoms and HRQOL. The sample consisted of 41 consecutive patients. At the start, during and end

Kerstin E. O. Öhrn; Per-Olow Sjödén; Ylva-Britt Wahlin; Marie Elf



Erosive potential of oral care products.  


Seven oral care products and orange juice as a positive control were tested for the erosive potential by immersing each enamel specimen (10 per group) into solutions of the various products for 10 and 20 min. Before and after the experiment Knoop surface hardness (SMH) was measured. The enamel microstructure before and after immersion was assessed by scanning electron microscopy and confocal laser scanning microscopy. Orange juice produced the most marked losses of hardness after 10 and 20 min. Among the dental hygiene products only the fluoride-free toothpaste produced a significant reduction of hardness after 10 as well as after 20 min. With the exception of Elmex gel, all tested oral care products led to a significant (p < 0.05) increase of enamel hardness. The results of the hardness measurements corresponded with the microstructure findings. It may, therefore, be concluded that the tested fluoride-containing oral care products do not exhibit any erosive potential, which could be picked up with the methodologies under study. PMID:11359059

Lussi, A; Hellwig, E



Papillary adenoma of type II pneumocytes might have malignant potential  

Microsoft Academic Search

Papillary adenoma of type II pneumocytes is a rare tumour. It is considered to be a benign neoplasm and is derived from immature cells in the bronchioloalveolar epithelium, however, its biological nature has not been elucidated. We report a case of an adenomatous tumour; a papillary adenoma of type II pneumocytes, which we regard as possessing malignant potential. Light microscopically,

M. Mori; R. Chiba; F. Tezuka; M. Kaji; T. Takahashi; T. Nukiwa; T. Kokubo



Oral mucositis and outcomes of allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies  

Microsoft Academic Search

Goals of the work  To assess the relationship between oral mucositis (OM) and adverse clinical and economic outcomes in patients with hematologic\\u000a malignancies receiving allogeneic hematopoietic stem-cell transplantation (HSCT).\\u000a \\u000a \\u000a \\u000a Materials and methods  A retrospective chart review study of 281 allogeneic HSCT recipients with hematologic malignancies was undertaken at a single\\u000a academic center. OM extent and severity were assessed across eight oropharyngeal sites

Montserrat Vera-Llonch; Gerry Oster; Colleen M. Ford; John Lu; Stephen Sonis



DNA content, malignancy grading and prognosis in T1 and T2 oral cavity carcinomas  

Microsoft Academic Search

Microscopic malignancy grading using the 8-factor system proposed by Jakobsson et al. (1973), the 4-factor system set up by Glanz and Eichhorn (1985), and DNA cytofluorometry were applied to thirteen T1 and thirty-seven T2 squamous cell carcinomas of the oral cavity, 9 with and 41 without metastases. There was a significant correlation between the presence of lymph node metastases (N1)

M Tytor; G Franzén; J Olofsson; U Brunk; B Nordenskjöld



Improved Oral Intake After Palliative Duodenal Stenting for Malignant Obstruction: A Prospective Multicenter Clinical Trial  

Microsoft Academic Search

OBJECTIVES:We sought to test the hypothesis that placement of a new nitinol duodenal self-expandable metallic stent (SEMS) for palliation of malignant gastroduodenal obstruction is effective and safe in allowing patients to tolerate an oral diet.METHODS:In a prospective multicenter study, SEMSs (Duodenal WallFlex, Boston Scientific) were placed to alleviate gastroduodenal obstruction in inoperable patients without the ability to tolerate solid food.

Michael Piesman; Richard A Kozarek; John J Brandabur; Douglas K Pleskow; Ram Chuttani; Viktor E Eysselein; William B Silverman; John J Vargo; Irving Waxman; Marc F Catalano; Todd H Baron; Willis G Parsons; Adam Slivka; David L Carr-Locke



Cytokeratins as epithelial differentiation markers in premalignant and malignant oral lesions.  


The keratin expression pattern in oral stratified epithelium is related to the cellular differentiation level. The normal pattern shows the keratin pair K5 and K14 in the stratum basale whereas K1 and K10, or K4 and K13, are the two pairs associated with differentiating suprabasal cells. Monoclonal and polyclonal antibodies to individual keratins (K10, K13 and K14) were used in a two-color immunofluorescence staining method to study their coexpression in single cells. Altered keratin expression in premalignant and malignant lesions indicated abnormal differentiation. Monospecific keratin antibodies were suggested to be useful for evaluation of epithelial differentiation changes in oral dysplasias and oral squamous cell carcinomas. PMID:1375644

Heyden, A; Huitfeldt, H S; Koppang, H S; Thrane, P S; Bryne, M; Brandtzaeg, P



Glomus tumor of uncertain malignant potential arising in the bronchus  

PubMed Central

Glomus tumor is usually a small, benign tumor and typically occurs in the dermis or subcutis or soft tissue of the extremities and rarely in the visceral locations. Its occurrence in the main bronchus is extremely rare. The current case reported a 30-year-old woman with dyspnea on exertion and hemoptysis, she had a glomus tumor which has large size, deep location and exhibits an infiltrative margin as well as increased atypical mitotic figures. These characteristics suggest malignant behavior. However, there is little data regarding glomus tumors arising in the bronchus, the need for caution in diagnosing this case as a malignant glomus tumor must be highlighted. Therefore, the diagnosis of bronchial glomus tumor of uncertain malignant potential was favored. To the best of our knowledge, both the type and the location of this glomus tumor are extremely rare. Accumulation of more cases are needed to clarify their diagnosis and significance since there is little data regarding glomus tumors arising in the bronchus.



FT-IR Spectroscopic Analysis of Normal and Malignant Human Oral Tissues  

NASA Astrophysics Data System (ADS)

FT-IR spectroscopy has been used to explore the changes in the vibrational bands of normal and oral squamous cell carcinoma (OSCC) tissues in the region 4000-400 cm-1. Significant changes in the spectral features were observed. The spectral changes were the results of characteristics structural alterations at the molecular level in the malignant tissues. These alterations include structural changes of proteins and possible increase of its content, an increase in the nucleic-to-cytoplasm ratio, an increase in the relative amount of DNA, an increase in the rate of phosphorylation process induced by carcinogenesis, a loss of hydrogen bonding of the C-OH groups in the amino acid residues of proteins, a decrease in the relative amount of lipids compared to normal epithelial oral tissues. The results of the present study demonstrate that the FT-IR technique has the feasibility of discriminating malignant from normal tissues and other pathological states in a short period of time and may detect malignant transformation earlier than the standard histological examination stage.

Krishnakumar, N.; Madhavan, R. Nirmal; Sumesh, P.; Palaniappan, Pl. Rm.; Venkatachalam, P.; Ramachandran, C. R.



Herpes simplex virus in oral mucosal ulcers in patients with hematological malignancy.  


Developments of oral mucosal ulcers induced by herpes simplex virus (HSV) were studied in patients with hematologic malignancy. Herpes simplex virus type-1 (HSV-1) was identified by immunological staining using virus-specific monoclonal antibodies in the epithelial cells of such ulcers from two patients with malignant lymphoma (ML), three with acute myeloblastic leukemia (AML), one with refractomy anemia with excess blasts, two with chronic myelocytic leukemia (CML), one with acute lymphoblastic leukemia (ALL) and one with aplastic anemia (AA). Herpes simplex virus type-2 (HSV-2) was also identified in an ulcer from a patient with AML. Isolation of HSV-1 was successful in the two patients with ML, one with CML, one with AML, the one with ALL and the one with AA. The ulcers developed on the tongue (four cases), buccal membrane (five cases), hard palate (one case), soft palate (one case), soft palate (one case) and gingiva (two cases). Only one patient with CML and one with AML had accompanying labial vesicular lesions. All patients except the one with AA had previously been given combination chemotherapy with anti-neoplastic agents. The results indicate that HSV may have an important role to play in the development of chemotherapy-related oral mucosal ulcers in patients with hematological malignancy. PMID:2558241

Shibuya, T; Moriyama, K; Harada, M; Okamura, T; Taniguchi, S; Akashi, K; Mori, R; Niho, Y



Malignant melanoma of the oral cavity. Review of the literature and experience in a Peruvian Population  

PubMed Central

Objective: To determine the epidemiological profile of malignant melanoma cases treated at the National Institute for Neoplastic Diseases “Dr. Eduardo Caceres Graziani” (INEN) over the period 1952 to 2008. Study Design: All clinical records with complete data of patients presenting a histopathological diagnosis of malignant melanoma of the oral cavity were reviewed. Data such as age, gender, location, tumor size, disease length, presence of metastasis, treatment received and year of admission were recorded. Results: During the study period 97 cases were found. The average age of patients was 52.85±1.6 years old mostly between 50 and 59 years old; the predominant gender was the female. The most common location was the palate and there was 58.8% of cases with a tumor size bigger than or equal to 4 cm. The length of the disease in 38.1% of the cases was longer than a year and in great part of the cases (69.1%) there was no metastasis. The treatment of choice was the surgery plus radiotherapy in 38.1% of the cases. According to the admission date it was also noted that the number of cases is increasing. Conclusion: The results of this study demonstrate a late diagnosis and an increasing frequency of this neoplasia in the oral cavity. Key words: Melanoma, oral cavity, epidemiology.

Gutierrez-Morales, Mario M.; Sacsaquispe-Contreras, Sonia J.; Sanchez-Lihon, Juvenal; Morales-Vadillo, Rafael



A Potential Therapeutic Strategy for Malignant Mesothelioma with Gene Medicine  

PubMed Central

Malignant mesothelioma, closely linked with occupational asbestos exposure, is relatively rare in the frequency, but the patient numbers are going to increase in the next few decades all over the world. The current treatment modalities are not effective in terms of the overall survival and the quality of life. Mesothelioma mainly develops in the thoracic cavity and infrequently metastasizes to extrapleural organs. A local treatment can thereby be beneficial to the patients, and gene therapy with an intrapleural administration of vectors is one of the potential therapeutics. Preclinical studies demonstrated the efficacy of gene medicine for mesothelioma, and clinical trials with adenovirus vectors showed the safety of an intrapleural injection and a possible involvement of antitumor immune responses. Nevertheless, low transduction efficiency remains the main hurdle that hinders further clinical applications. Moreover, rapid generation of antivector antibody also inhibits transgene expressions. In this paper, we review the current status of preclinical and clinical gene therapy for malignant mesothelioma and discuss potential clinical directions of gene medicine in terms of a combinatory use with anticancer agents and with immunotherapy.

Tada, Yuji; Shimada, Hideaki; Hiroshima, Kenzo; Tagawa, Masatoshi



Endovascular Therapy for Management of Oral Hemorrhage in Malignant Head and Neck Tumors  

SciTech Connect

Purpose. To evaluate the efficacy and safety of endovascular therapy in oral hemorrhage from malignant head and neck tumors. Methods. Ten patients (mean age 56 years) with oral hemorrhage caused by malignant head and neck tumors underwent a total of 13 emergency embolization procedures using gelatin sponge particles, steel and/or platinum coils, or a combination of these embolic materials. Angiographic abnormalities, technical success rate, clinical success rate, recurrence rate, complications, hemostatic period, hospital days, survival days, and patient outcome were all analyzed. Results. Angiographic abnormalities were identified during 85% of procedures (11/13). The technical success rate was 100% (13/13 procedures). The primary and secondary clinical success rates were 77% (10/13 procedures) and 67% (2/3 procedures), respectively. The overall clinical success rate was 92%, and the recurrence rate was 22% (2/9 procedures) in patients whom we were able to observe during the 1-month period after embolization. No major complications occurred. Several patients in whom gelatin sponge particles had been used complained of transient local pain after the procedure. The median hemostatic period was 71 days (range 0-518 days). Median hospital and survival days were 59 days (range 3-209 days) and 141 days (range 4-518 days), respectively. Three patients survived and 7 patients died during the observation period. Only 1 of these 7 patients died from hemorrhage. Conclusion. In conclusion, our findings suggest that endovascular therapy is an effective, safe, and repeatable treatment for oral hemorrhage caused by malignant head and neck tumors.

Kakizawa, Hideaki, E-mail:; Toyota, Naoyuki; Naito, Akira; Ito, Katsuhide [Graduate School of Biomedical Science, Hiroshima University, Department of Radiology, Division of Medical Intelligence and Informatics Programs for Applied Biomedicine (Japan)



Reproducibility of two malignancy grading systems with reportedly prognostic value for oral cancer patients.  


Supplementary prognostic factors should be added to the TNM classification for oral squamous cell carcinomas in order to optimize its clinical value. We have recently published two prognostically valuable malignancy grading systems based on histopathology and immunohistology of the most invasive cells in oral squamous cell carcinomas (OSCCs). However, a major problem with classifications based on histologic features is frequent lack of interobserver agreement which limits the clinical value of subjective histologic classifications. Thirty-eight file cases of OSCCs were therefore graded by three pathologists according to criteria of the histologic malignancy grading system which includes 5 morphologic features, each graded from 1 to 4. Agreement was calculated by kappa statistics, which showed that interobserver agreement was not optimal, but significantly better than by chance alone. We also studied the reproducibility of grading of immunohistologic membrane expression of a tumor-associated marker (blood group antigen H), and found a similar level of agreement. We conclude that the clinical value of our grading systems will increase by improving reproducibility. PMID:1719194

Bryne, M; Nielsen, K; Koppang, H S; Dabelsteen, E



Incidental detection of an occult oral malignancy with autofluorescence imaging: a case report  

PubMed Central

Background Autofluorescence imaging is used widely for diagnostic evaluation of various epithelial malignancies. Cancerous lesions display loss of autofluorescence due to malignant changes in epithelium and subepithelial stroma. Carcinoma of unknown primary site presents with lymph node or distant metastasis, for which the site of primary tumour is not detectable. We describe here the use of autofluorescence imaging for detecting a clinically innocuous appearing occult malignancy of the palate which upon pathological examination was consistent with a metastatic squamous cell carcinoma. Case Description A submucosal nodule was noted on the right posterior hard palate of a 59-year-old white female during clinical examination. Examination of this lesion using a multispectral oral cancer screening device revealed loss of autofluorescence at 405 nm illumination. An excisional biopsy of this nodule, confirmed the presence of a metastatic squamous cell carcinoma. Four years ago, this patient was diagnosed with metastatic squamous cell carcinoma of the right mid-jugular lymph node of unknown primary. She was treated with external beam irradiation and remained disease free until current presentation. Conclusion This case illustrates the important role played by autofluorescence tissue imaging in diagnosing a metastatic palatal tumour that appeared clinically innocuous and otherwise would not have been biopsied.



Role of human papillomavirus and its detection in potentially malignant and malignant head and neck lesions: updated review.  


Head and neck malignancies are characterized by a multiphasic and multifactorial etiopathogenesis. Tobacco and alcohol consumption are the most common risk factors for head and neck malignancy. Other factors, including DNA viruses, especially human papilloma virus (HPV), may also play a role in the initiation or development of these lesions. The pathways of HPV transmission in the head and neck mucosal lesions include oral-genital contact, more than one sexual partner and perinatal transmission of HPV to the neonatal child. The increase in prevalence of HPV infection in these lesions may be due to wider acceptance of oral sex among teenagers and adults as this is perceived to be a form of safe sex. The prevalence of HPV in benign lesions as well as malignancies has been assessed by many techniques. Among these, the polymerase chain reaction is the most sensitive method. Review of literature reveals that HPV may be a risk factor for malignancies, but not in all cases. For confirmation of the role of HPV in head and neck squamous cell carcinoma, large population studies are necessary in an assortment of clinical settings. Prophylactic vaccination against high-risk HPV types eventually may prevent a significant number of cervical carcinomas. Of the two vaccines currently available, Gardasil (Merck & Co., Inc.) protects against HPV types 6, 11, 16 and 18, while the other vaccine, Cervarix (GlaxoSmithKline, Rixensart, Belgium) protects against HPV types 16 and 18 only. However, the HPV vaccine has, to the best of our knowledge, not been tried in head and neck carcinoma. The role of HPV in etiopathogenesis, prevalence in benign and malignant lesions of this area and vaccination strategies are briefly reviewed here. PMID:19555477

Chaudhary, Ajay Kumar; Singh, Mamta; Sundaram, Shanthy; Mehrotra, Ravi



iNOS: A Potential Therapeutic Target for Malignant Glioma.  


Glioblastoma is the most aggressive adult primary brain tumor. Although progress has been made in understanding the molecular mechanisms underlying these tumors, current treatments are ineffective. Recent studies have identified iNOS as a critical regulator of glial transformation downstream of EGFRvIII/STAT3 signaling, a key oncogenic pathway in glioblastoma. STAT3 directly binds the promoter of the iNOS gene and thereby stimulates its expression. Importantly, inhibition of iNOS by genetic and pharmacological approaches impedes glial cell proliferation, invasiveness, and tumor growth in vivo. iNOS expression is also elevated in a population of human brain tumor stem cells (BTSCs), and iNOS is required for BTSC proliferation and tumorigenesis. Together, these findings suggest that development of iNOS-targeted therapies may prove valuable in the treatment of glioblastoma. Here, we review our current understanding of iNOS signaling in the regulation of glioblastoma pathogenesis and the potential mechanisms by which iNOS inhibition might suppress the malignant behavior of these devastating tumors. PMID:23590833

Jahani-Asl, A; Bonni, A



Plasminogen activators in normal and malignant oral epithelium in vivo and in vitro.  


Urokinase-type (uPA) and tissue-type (tPA) plasminogen activators were identified by fibrinolytic autography in the sulcus epithelium of human gingival mucosa but not in the orthokeratinized gingival epithelium. Fibrinolytic activity was present only over blood vessels in frozen sections of oral squamous cell carcinomas, the malignant epithelial cells showing no plasminogen activator activity. Plasminogen activators could not be demonstrated in either the sulcus or gingival epithelium by immunofluorescence, but both uPA and tPA were found in occasional squamous carcinoma cells. Fibrinolytic activity of culture fluids from epithelial explants grown in vitro from human gingival mucosa showed marked variation, but activity was much higher in the culture supernatants than in the cell lysates. Fibrinolytic activity of culture fluids from epithelial explants of squamous cell carcinomas was low both in supernatants and lysates. Zymogram overlays of sodium dodecyl sulphate-polyacrylamide electrophoretic gels from culture supernatants showed that the low fibrinolytic activity of culture supernatants of oral squamous cell carcinomas was due to the associated presence of plasminogen activator inhibitors. The fibrinolytic activity in the zymogram was due predominantly to uPA but some lysis was due also to tPA. PMID:1417524

Barlow, Y; Southam, J C



Malignant lymphoma of the oral cavity and the maxillofacial region: Overall survival prognostic factors  

PubMed Central

Objective: To identify the overall survival and prognostic factors of malignant lymphoma of the oral cavity and the maxillofacial region. Study Design: Clinical records data were obtained in order to determine overall survival at 2 and 5 years, the individual survival percentage of each possible prognostic factor with the actuarial technique, and the survival regarding the possible prognostic factors with the actuarial technique and the Log-rank and Cox’s regression tests. Results: Of 151 subjects, an overall survival was 60% at 2 years, and 45% at 5 years. The multivariate analysis demonstrated statistically significant differences for clinical stage (p=0.002), extranodal involvement (p=0.030), presence of human immunodeficiency virus (p=0.032), and presence of Epstein-Barr virus (p=0.010). Conclusion: The advanced clinical stage and the larger number of involved extranodular sites are related to a lower overall survival, as well as, the presence of previous infections such as the human immunodeficiency and the Epstein-Barr virus. Key words:Lymphoma, oral cavity, survival.

Morales-Vadillo, Rafael; Sacsaquispe-Contreras, Sonia J.; Barrionuevo-Cornejo, Carlos; Montes-Gil, Jaime; Cava-Vergiu, Carlos E.; Soares, Fernando A.; Chaves-Netto, Henrique D M.; Chaves, Maria G A M.



DNA ploidy analysis by image cytometry helps to identify oral epithelial dysplasias with a high risk of malignant progression.  


Abnormal DNA content (aneuploidy) has been associated with malignant and premalignant epithelial lesions. The presence of aneuploidy in tumours at an early stage and in dysplastic lesions suggests that analysis of DNA content may be a useful marker for determination of prognosis in these lesions. The aim of this study was to use DNA image cytometry to evaluate aneuploidy in oral dysplastic lesions and to determine whether aneuploidy is associated with malignant progression. Forty-two lesions of oral epithelial dysplasias (OED) that had progressed to oral squamous cell carcinoma (OSCC) and 44 lesions that did not progress were analysed for DNA ploidy using image cytometry of nuclear monolayers prepared from paraffin-embedded tissue. Forty-two OSCC that had arisen from the OED cases and five samples of normal oral mucosa samples (NOM) were also examined. Aneuploidy was found in 14/42 (33.3%) of the OED that progressed, but in only 5/44 (11.3%) of OED that did not progress (p=0.01). A total of 19 OED were aneuploid of which 74% showed malignant progression compared to only 42% of the diploid lesions. The sensitivity and specificity of DNA image cytometry to detect cases with high risk of malignant progression was 0.33 and 0.88, respectively. The PPV and NPV were 0.74 and 0.58. We conclude that aneuploid oral dysplastic lesions have a high risk of malignant progression and that DNA image cytometry might help to identify those lesions most at risk. PMID:18805043

Torres-Rendon, A; Stewart, R; Craig, G T; Wells, M; Speight, P M



Genetic polymorphisms of matrix metalloproteinases and their inhibitors in potentially malignant and malignant lesions of the head and neck  

PubMed Central

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that are capable of cleaving all extra cellular matrix (ECM) substrates. Degradation of matrix is a key event in progression, invasion and metastasis of potentially malignant and malignant lesions of the head and neck. It might have an important polymorphic association at the promoter regions of several MMPs such as MMP-1 (-1607 1G/2G), MMP-2 (-1306 C/T), MMP-3 (-1171 5A/6A), MMP-9 (-1562 C/T) and TIMP-2 (-418 G/C or C/C). Tissue inhibitors of metalloproteinases (TIMPs) are naturally occurring inhibitors of MMPs, which inhibit the activity of MMPs and control the breakdown of ECM. Currently, many MMP inhibitors (MMPIs) are under development for treating different malignancies. Useful markers associated with molecular aggressiveness might have a role in prognostication of malignancies and to better recognize patient groups that need more antagonistic treatment options. Furthermore, the introduction of novel prognostic markers may also promote exclusively new treatment possibilities, and there is an obvious need to identify markers that could be used as selection criteria for novel therapies. The objective of this review is to discuss the molecular functions and polymorphic association of MMPs and TIMPs and the possible therapeutic aspects of these proteinases in potentially malignant and malignant head and neck lesions. So far, no promising drug target therapy has been developed for MMPs in the lesions of this region. In conclusion, further research is required for the development of their potential diagnostic and therapeutic possibilities.



[The diagnosis value of malignant tumors in the Oral and Maxillofacial region using healthy person's free radical of hair  


Electron spin Resonance(ESR) was used to determine the free radical of hair from 324 cases.These cases included 185 healthy persons,33 benign tumor patients,84 malignant cases and 22 oral mucosa disease cases.The determined results were controlled with pathologic diagnosis to analyse the accordance. The result showed the positive rates of above mentioned cases were 5.9%,6.1%,84.52%and 9.1% respectively.The significant differences were observed when comparing the results of malignant cases with healthy person and benign tumor cases with healthy person and benign tumor cases(P<0.01).The ESR saturation power points of some malignant cases rose to above border-line(>10.0mW) after treatment.These results indicated using ESR to diagnosis early malignant cases and follow treatment effect possess certain clinical value. PMID:15160094

Chen, J W; Qiu, W L; He, R G; Lin, G C; Zhang, Z Y



Quantitative Cytochemical Detection of Malignant and Potentially Malignant Cells in the Colon1  

Microsoft Academic Search

It was found to be possible to distinguish malignant cells from normal cells by using an oxygen-sensitive tetrazolium salt (neotetrazolium) for the histochemical demonstration of glucose-6-phosphate dehydrogenase activity in cryostat sections of human colon. We have studied 12 cases of established adenocarcinoma of the colon in addition to 4 of ulcerative colitis and 4 of adenomatous polyposis (polyposis coli). In

Pranab K. Das; Hitendra R. H. Patel; Cornelis J. F. Van Noorden



Secondary malignancies of the uterine cervix: a potential diagnostic pitfall.  


The occurrence of a secondary malignancy in the uterine cervix is a very rare event. In the vast majority of cases, this secondary involvement concerns direct spread of a uterine malignancy to the cervix. However, cancer of the ovary, breast, stomach, gallbladder, pancreas and lung has been reported to metastasize to the uterine cervix by hematogenous route. In this context, secondary lesions of the uterine cervix, in particular those of non-epithelial and extra-genital origin, are sufficiently rare to be overlooked, which might result in inappropriate diagnosis with disappointing consequences in terms of treatment planning. We report a single-institution consecutive series of 144 cases of secondary malignancy of the uterine cervix, emphasizing the morphological and immunohistochemical criteria required to arrive at a correct final diagnosis. Secondary malignancies of the uterine cervix have a protean appearance and can present with a wide spectrum of symptoms. Almost invariably metastases to the cervix signal devastating spread to many different organs. Histopathology, as well as immunohistochemical features and close collaboration between clinicians and pathologists, is essential to arrive at a correct final diagnosis. PMID:23748795

Zannoni, Gian Franco; Vellone, Valerio Gaetano; Petrillo, Marco; Fadda, Guido; Rossi, Esther Diana; Scambia, Giovanni; Carbone, Arnaldo



A quantitative investigation of immunocytochemically stained blood vessels in normal, benign, premalignant and malignant human oral cheek epithelium  

Microsoft Academic Search

The present study was designed to determine whether increased vascularity occurs during malignant transformation of human oral cheek epithelium. Nine normal (N) samples were taken from the resection margins of benign lesions; the pathological lesions were classified as chronic inflammation (CI; n=11), fibrous hyperplasia (FH; n=12), lichen planus (LIP; n=8), dysplasia (DYS; n=5), squamous cell carcinoma (SCC; n=25; well differentiated

G. L. Tipoe; F. H. White; Y. Jin; L. Yang



Oral Health Scales: Design of an Oral Health Scale of Infectious Potential  

PubMed Central

Objectives: In this paper we propose a new Global Oral Health Scale that will allow the infectious potential of the oral cavity, clinically manifest as local and focal infections, to be condensed into a single parameter. Study Design: Based on a number of oral health scales previously designed by our group, we designed a final version that incorporates dental and periodontal variables (some of them evaluated using corroborated objective indices) that reflect the presence of caries and periodontal disease. Results: The application of the proposed oral health scale requires the examination of 6 sites per tooth (mesio-buccal, medio-buccal, disto-buccal, disto-lingual, medio-lingual and mesio-lingual). The following variables are analysed: number of tooth surfaces with supragingival plaque, determined using the O’Leary index; number of teeth with caries and the severity of the caries; number of tooth surfaces with gingival inflammation, determined using the Ainamo and Bay index; and number of tooth surfaces with pockets ?4 mm and severity of the pockets. These variables are then grouped into 2 categories, dental and periodontal. The final grades of dental and periodontal health correspond to the grades assigned to a least 2 of the 3 variables analysed in each of these categories. The category (dental or periodontal) with the highest grade is the one that determines the grade of the Global Oral Health Scale. Conclusion: This scale could be particularly useful for the epidemiological studies comparing different populations and for analysis of the influence of distinct degrees of oral health on the development of certain systemic diseases. Key words:Scale, oral health, infectious potential, systemic disease.

Relvas, Marta; Diz, Pedro; Seoane, Juan



Estimation of serum malondialdehyde in potentially malignant disorders and post-antioxidant treated patients: A biochemical study  

PubMed Central

Background: Tobacco causes the generation of free radicals and reactive oxygen species (ROS) which are responsible for the high rate of lipid peroxidation. Malondialdehyde (MDA) is the most widely used agent to estimate the extent of lipid peroxidation. Timely diagnosis of the condition followed by supplementation with antioxidants like beta-carotene, pro-vitamin A, vitamin A, vitamin C, vitamin E, lipoic acid, zinc, selenium, and spirulina can prevent potentially malignant disorders. Materials and Methods: In this study, serum MDA was measured according to the method of Buege, in 15 normal samples and 15 patients who were histopathologically diagnosed with potentially malignant disordered and they were prescribed with antioxidants for a period of 4 week-time following which potentially malignant patients serum MDA was analyzed again to determine the extent of peroxidation reactions. Results: The mean serum MDA level in Group C1 was 0.7900 ± 0.2336 ?M/L were as the mean serum MDA level of Group S1 was 2.478 ± 0.50756 ?M/L and the values between them were highly significant. The values between C1 and S2 were found to be statistically significant. The mean serum MDA of S2 was 2.160 ± 0.41252 ?M/L and the values were significant when compared to S1. Conclusion: Serum MDA estimation in oral pre-cancer would serve in determining the extent of lipid peroxidation. Diagnosis of patients and administration of antioxidants has proven to be effective in declining the ROS and thus reducing the extent of damage on the cells. MDA may serve as a diagnostic tool in the estimation of oral pre-cancer and in evaluation of post-treated cases.

D'souza, Deepa; Subhas, Babu G; Shetty, Shishir Ram; Balan, Preethi



The spectrum of hematologic malignancies involving the pancreas: potential clinical mimics of pancreatic adenocarcinoma.  


Hematologic malignancies often involve the pancreas, causing potential diagnostic pitfalls and, rarely, potentially avoidable surgical resection. We review the spectrum of hematologic malignancies involving the pancreas and describe features useful in preoperative distinction from adenocarcinoma. Archived clinical, pathologic, and radiologic data (1965 to present) for hematologic malignancies involving the pancreas were reviewed and compared with the data for 157 surgically resected pancreatic adenocarcinomas. Of 42 cases, 27 (64%) were clinically "suspicious" for hematologic malignancies. Of the remaining 15 cases, 4 patients underwent resection for presumed pancreatic adenocarcinoma. Isolated pancreatic masses proved most difficult to identify clinically. Significant factors in distinguishing hematologic malignancies from adenocarcinoma included history of hematologic malignancy, young age, large tumor size, low CA19-9 level, B symptoms, and lack of jaundice or diabetes mellitus. Various hematologic malignancies involve the pancreas, most commonly diffuse large B-cell lymphoma. Pancreatic masses are usually correctly identified clinically. Preoperative and operative sampling is strongly recommended when hematologic malignancies cannot be excluded. PMID:22338053

Rock, Jonathan; Bloomston, Mark; Lozanski, Gerard; Frankel, Wendy L



Human RGM249-derived small RNAs potentially regulate tumor malignancy.  


The human noncoding RNA gene RGM249 has been shown to regulate the degree of cancer cell differentiation. In this study, we investigated the effects of 3 microRNA-like molecules digested from RGM249 on the loss of malignant properties in cancer cells in immunodeficient KSN/Slc mice. We utilized small interfering RNAs (siRNAs) alone or in combination with a cationized drug delivery system (DDS) consisting of atelocollagen or gelatin hydrogel microspheres. The results demonstrated growth inhibition and apoptosis and the inhibition of both neovascularization and metastasis, indicating that the DDSs effectively infiltrated the majority of tumor cells in vivo. Systemic administration of the 3 siRNAs inhibited the metastatic ability of malignant cells. Cotransfection of these siRNAs exerted a regulatory effect upon the genes involved in differentiation, pluripotency, and proliferation in cancer cells. These results suggest that RGM249-derived oligonucleotides may be involved in the regulation of metastasis, proliferation, and differentiation in vivo, and that the tested siRNAs may therefore represent a new anticancer therapeutic approach. PMID:23988019

Miura, Norimasa; Shimizu, Mika; Shinoda, Waka; Tsuno, Satoshi; Sato, Reina; Wang, Xinhui; Jo, Jun-Ichiro; Tabata, Yasuhiko; Hasegawa, Junichi



The Potential Role of Aurora Kinase Inhibitors in Haematological Malignancies  

PubMed Central

Summary Aurora kinases play an important role in the control of the cell cycle and have been implicated in tumourigenesis in a number of cancers. Among the haematological malignancies, overexpression of Aurora kinases has been reported in acute myeloid leukaemia, chronic myeloid leukaemia, acute lymphoblastic leukaemia, multiple myeloma, aggressive non-Hodgkin lymphoma and Hodgkin lymphoma. A large number of Aurora kinase inhibitors are currently in different stages of clinical development. In addition to varying in their selectivity for the different Aurora kinases, some also have activity directed at other cellular kinases involved in important molecular pathways in cancer cells. This review summarizes the biology of Aurora kinases and discusses why they may be good therapeutic targets in different haematological cancers. We describe preclinical data that has served as the rationale for investigating Aurora kinase inhibitors in different haematological malignancies, and summarize published results from early phase clinical trials. While the anti-tumour effects of Aurora kinase inhibitors appear promising, we highlight important issues for future clinical research and suggest that the optimal use of these inhibitors is likely to be in combination with cytotoxic agents already in use for the treatment of various haematological cancers.

Farag, Sherif S.



Oral Bacteria as Potential Probiotics for the Pharyngeal Mucosa?  

PubMed Central

The research described here was aimed at the selection of oral bacteria that displayed properties compatible with their potential use as probiotics for the pharyngeal mucosa. We included in the study 56 bacteria newly isolated from the pharynges of healthy donors, which were identified at the intraspecies level and characterized in vitro for their probiotic potential. The experiments led us to select two potential probiotic bacterial strains (Streptococcus salivarius RS1 and ST3) and to compare them with the prototype oral probiotic S. salivarius strain K12. All three strains efficiently bound to FaDu human epithelial pharyngeal cells and thereby antagonized Streptococcus pyogenes adhesion and growth. All were sensitive to a variety of antibiotics routinely used for the control of upper respiratory tract infections. Immunological in vitro testing on a FaDu layer revealed different responses to RS1, ST3, and K12. RS1 and ST3 modulated NF-?B activation and biased proinflammatory cytokines at baseline and after interleukin-1? (IL-1?) induction. In conclusion, we suggest that the selected commensal streptococci represent potential pharyngeal probiotic candidates. They could display a good degree of adaptation to the host and possess potential immunomodulatory and anti-inflammatory properties.

Guglielmetti, Simone; Taverniti, Valentina; Minuzzo, Mario; Arioli, Stefania; Stuknyte, Milda; Karp, Matti; Mora, Diego



Immunohistochemical evaluation of oral epithelial dysplasia using cyclin-D1, p27 and p63 expression as predictors of malignant transformation  

PubMed Central

Objective: To evaluate the degree of expression of cyclin-D1, p27 and p63 in mild, moderate and severe dysplasia using immunohistochemical evaluation in order to illustrate their prognostic value and attempt to propose a molecular grading system for oral epithelial dysplasia. Materials and Methods: The analysis included thirty cases of mild, moderate and severe dysplasia from Department of Oral and Maxillofacial Pathology, Saveetha Dental College, Chennai after a critical review of the Hematoxylin and Eosin (H and E) stained sections. They were subjected to immunohistochemical evaluation using the markers cyclin-D1, p27 and p63. The assessment of the expression based on staining intensity and distribution of immunohistochemical staining of the various markers was analyzed followed by statistical analysis. Results: A highly significant increase in the expression of cyclin-D1 (P < 0.000) and p63 (P < 0.001) and a moderately significant decrease in the expression of p27 (P < 0.012) with the increasing severity of dysplasia was observed in our study. Conclusions: The result of our research affirms the fact that the increase in the expression of markers of cell cycle regulators such as cyclin D1, decrease in the expression of cell cycle inhibitors like p27 and increased expression of p63 in parallel with the increasing severity of dysplasia, emphasizes the use of immunohistochemical markers cyclin D1, p27 and p63 as prognostic markers for better understanding the behaviour of these potentially malignant disorders aiming towards proposing a molecular grading system for oral epithelial dysplasia to enable timely management prior to their possible malignant transformation.

Ramasubramanian, Abilasha; Ramani, Pratibha; Sherlin, Herald J.; Premkumar, Priya; Natesan, Anuja; Thiruvengadam, Chandrasekar



S-allylcysteine modulates the expression of E-cadherin and inhibits the malignant progression of human oral cancer.  


Oral cancer is a prevalent type of cancer in Asian countries. Several studies indicated that garlic extracts such as diallyl disulfide (DADS) and diallyl trisulfide (DATS) have anticancer effects. However, the inhibitory effects of water soluble garlic extracts, S-allylcysteine (SAC), on the malignant progression of oral cancer have not been studied well yet. Thus, the purpose of this study was to investigate the inhibitory effects of SAC on the proliferation and progression of human oral squamous cancer CAL-27 cells. In the present study, we demonstrated that SAC dose dependently inhibited the growth of human oral squamous cancer cells. Our results showed that SAC induced the expression of E-cadherin adhesion molecule. Immunocytochemical staining result also revealed that SAC could restore the distribution of E-cadherin molecule on cell membrane. We further demonstrated that SAC stabilized the adherent junction complex of E-cadherin/beta-catenin in oral cancer cells. Treatment with the MAPK/MEK specific inhibitor, PD098059, could up-regulate the expression of E-cadherin molecule. Furthermore, SAC significantly inhibited the activation of MAPK/ERK signaling pathway. These findings were associated with the down-regulation of the SLUG repressor protein. In conclusion, our results indicated that SAC effectively inhibited the proliferation, up-regulated the expression of E-cadherin molecule and stabilized the E-cadherin/beta-catenin adherent junction complex in human oral squamous cancer cells. The mechanism of action was in part through the suppression of MAPK/ERK signaling pathway and down-regulation of the SLUG repressor protein. PMID:19157822

Tang, Feng-Yao; Chiang, En-Pei Isabel; Chung, Jing-Gung; Lee, Hong-Zin; Hsu, Chia-Yun



Factors affecting swallow outcome following treatment for advanced oral and oropharyngeal malignancies.  


BACKGROUND: Treatment for tumors of the oral cavity and the oropharynx disrupts normal swallow function. The ability for oral diet postoperatively varies and may be influenced by surgery and patient-related factors. METHODS: In all, 114 patients treated with surgery with and without chemoradiotherapy for advanced oral/oropharyngeal cancer were recruited. Clinicopathologic tumor parameters and reconstruction modalities were recorded. Swallow function was determined by oral intake, using the Functional Oral Intake Scale (FOIS) pretreatment and posttreatment. RESULTS: The median time to first attaining swallow function was 14 days. Patients were less likely to attain tube independence within 1 year of surgery if they received radiotherapy or had a low FOIS score preoperatively. Patients' time to first attaining swallow function postsurgery was inversely related to the FOIS score presurgery. CONCLUSIONS: Swallow function recovery postsurgery is better in patients with higher FOIS presurgery, smaller tumors, and no requirement for radiotherapy. © 2013 Wiley Periodicals, Inc. Head Neck, 2013. PMID:23559533

Kalavrezos, Nicholas; Cotrufo, Stefano; Govender, Roganie; Rogers, Pauline; Pirgousis, Phil; Balasundram, Sathesh; Lalabekyan, Bagrat; Liew, Colin



Prognostic value of histobiological factors (malignancy grading and AgNOR content) assessed at the invasive tumour front of oral squamous cell carcinomas.  

PubMed Central

Tumour cells at the invasive front of carcinomas have been found to differ substantially from the rest of tumour cells in a variety of human cancers. The present multivariate survival analysis of 94 oral squamous cell carcinomas (OSCCs) revealed that both the argyrophilic nucleolar organizer regions-associated protein (AgNOR) content of invading tumour cells and a multiparametric histopathological tumour front grade were significantly and independently associated with tumour-related death, irrespective of conventional Broders' grade and clinical stage of the tumours. High tumour front scores and AgNOR content at the invasive OSCC front thus seem to reflect increased malignant potential. Proliferative activity, assessed by standardized AgNOR analysis, most probably represents one of the biological features underlying the usefulness of evaluating the invasive tumour front. Images Figure 2

PiffkA?, J.; BA nkfalvi, A.; Ofner, D.; Bryne, M.; Rasch, D.; Joos, U.; BA?cker, W.; Schmid, K. W.



Evaluation of TGF-? and EGFR Expression in Oral Leukoplakia and Oral Submucous Fibrosis by Quantitative Immunohistochemistry  

Microsoft Academic Search

Objective: Oral leukoplakia (OL) and oral submucous fibrosis (OSMF) are clinically distinct preneoplastic states that precede the development of oral squamous cell carcinoma. Recently, attempts are being made to identify specific molecular event(s) as prognostic markers to identify oral precancerous lesions with higher malignant potential. The goal of the present study was to evaluate the expression of EGFR and its

Mythily Srinivasan; Scott D. Jewell



Serous tumors of low malignant potential of the ovary-molecular pathology: part 2  

Microsoft Academic Search

A progressive development from serous tumors of low malignant potential (SLMP) to bluntly invasive serous carcinoma has been suggested in parallel to the concept of adenoma-carcinoma sequence in colorectal carcinomas. However, recent genetic data enforces a reassessment of the concept that SLMP tumors represent precursor lesions to invasive serous carcinoma. Despite the benign nature of the majority of these tumors,

S. Hauptmann; M. Dietel



Epithelial ovarian tumors of low malignant potential: the role of microinvasion  

Microsoft Academic Search

OBJECTIVE: To identify prognostic factors that may be used to predict an aggressive disease course and poor outcome in patients with epithelial ovarian tumors of low malignant potential (borderline tumors).METHODS: Data on 126 patients with ovarian borderline tumors were analyzed with regard to demographic characteristics, staging, presence of microinvasion, duration of follow-up, recurrence rate, rate of recurrence as invasive disease,

Barbara M. Buttin; Thomas J. Herzog; Matthew A. Powell; Janet S. Rader; David G. Mutch



Protein and mRNA expression of simple epithelial keratins in normal, dysplastic, and malignant oral epithelia.  

PubMed Central

Simple epithelial keratins K7, K8, and K18 are present in no more than trace amounts in normal stratified squamous epithelial but have been reported in squamous cell carcinomas. With the aim of determining the level at which keratin synthesis is regulated in vivo, we have compared the expression of mRNA by in situ hybridization and protein by immunohistochemistry for K7, K8, and K18 in a series of normal, dysplastic, and malignant oral epithelia. In normal epithelia mRNAs for K7, K8, and K18 were present in basal and lower spinous cells but adjacent sections were generally negative for the respective proteins. In severe dysplasia there was irregular suprabasal extension of K8 and K18 mRNAs in all cases and their proteins were expressed in more than half of the cases. The carcinomas expressed K8 and K18 mRNAs homogeneously and were strongly reactive for these keratin proteins but K7 expression appeared reduced in malignancy. These results are consistent with the post-transcriptional regulation of K7, K8, and K18 expression in normal epithelia and the presence of their proteins in dysplastic and malignant epithelia suggests the release of these epithelial cells from a post-transcriptional block on K8 and K18 translation. Alternatively, rapid degradation of K8 and K18 protein might be occurring in normal epithelia but be suppressed in dysplasia and malignancy. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8

Su, L.; Morgan, P. R.; Lane, E. B.



Expression of parathyroid hormone-related protein confers malignant potential to mucoepidermoid carcinoma  

PubMed Central

Parathyroid hormone-related protein (PTHrP) is known to induce bone resorption by activating RANKL as well as PTH. PTHrP plays a central role in humoral hypercalcemia, and its expression has been reported to be closely associated with bone metastasis of breast carcinoma. PTHrP expression in oral squamous carcinoma cell lines was investigated, and PTHrP was expressed in oral squamous cell carcinoma cell lines similar to that in a prostate carcinoma cell line. Mucoepidermoid carcinoma is the most common malignant salivary gland tumor composed of different types of cells including a squamous component. Its clinical behavior is highly variable and ranges from slow-growing and indolent to locally aggressive and highly metastatic. We examined the PTHrP expression in mucoepidermoid carcinoma and assessed the significance of its correlation with clinicopathological features. Immunohistochemical detection of PTHrP was carried out in 21 cases of mucoepidermoid carcinoma in the head and neck region. PTHrP was highly detectable in intermediate and epidermoid cells, and abundant expression of PTHrP in intermediate cells had a significant association with cancer malignancy, including lymph node metastasis and/or tumor recurrence. These results suggest that PTHrP expression can be used as a prognostic factor for mucoepidermoid carcinoma.




Expression of parathyroid hormone-related protein confers malignant potential to mucoepidermoid carcinoma.  


Parathyroid hormone-related protein (PTHrP) is known to induce bone resorption by activating RANKL as well as PTH. PTHrP plays a central role in humoral hypercalcemia, and its expression has been reported to be closely associated with bone metastasis of breast carcinoma. PTHrP expression in oral squamous carcinoma cell lines was investigated, and PTHrP was expressed in oral squamous cell carcinoma cell lines similar to that in a prostate carcinoma cell line. Mucoepidermoid carcinoma is the most common malignant salivary gland tumor composed of different types of cells including a squamous component. Its clinical behavior is highly variable and ranges from slow-growing and indolent to locally aggressive and highly metastatic. We examined the PTHrP expression in mucoepidermoid carcinoma and assessed the significance of its correlation with clinicopathological features. Immunohistochemical detection of PTHrP was carried out in 21 cases of mucoepidermoid carcinoma in the head and neck region. PTHrP was highly detectable in intermediate and epidermoid cells, and abundant expression of PTHrP in intermediate cells had a significant association with cancer malignancy, including lymph node metastasis and/or tumor recurrence. These results suggest that PTHrP expression can be used as a prognostic factor for mucoepidermoid carcinoma. PMID:23588777

Nagamine, Kyosuke; Kitamura, Tetsuya; Yanagawa-Matsuda, Aya; Ohiro, Yoichi; Tei, Kanchu; Hida, Kyoko; Higashino, Fumihiro; Totsuka, Yasunori; Shindoh, Masanobu



Expression Profiling of Serous Low Malignant Potential, Low-Grade, and High-Grade Tumors of the Ovary  

Microsoft Academic Search

Papillary serous low malignant potential (LMP) tumors are characterized by malignant features and metastatic potential yet display a benign clinical course. The role of LMP tumors in the development of invasive epithelial cancer of the ovary is not clearly defined. The aim of this study is to determine the relationships among LMP tumors and invasive ovarian cancers and identify genes

Tomas Bonome; Ji-Young Lee; Dong-Choon Park; Mike Radonovich; Cindy Pise-Masison; John Brady; Ginger J. Gardner; Wing H. Wong; J. Carl Barrett; Karen H. Lu; Anil K. Sood; David M. Gershenson; Samuel C. Mok; Michael J. Birrer



Role of human papillomavirus and its detection in potentially malignant and malignant head and neck lesions: updated review  

Microsoft Academic Search

Head and neck malignancies are characterized by a multiphasic and multifactorial etiopathogenesis. Tobacco and alcohol consumption are the most common risk factors for head and neck malignancy. Other factors, including DNA viruses, especially human papilloma virus (HPV), may also play a role in the initiation or development of these lesions. The pathways of HPV transmission in the head and neck

Ajay Kumar Chaudhary; Mamta Singh; Shanthy Sundaram; Ravi Mehrotra



Double malignant neoplasms occurring long after local radiation to the oral mucosa  

Microsoft Academic Search

A 59-year-old woman who had received cobalt-60 (60Co) interstitial radiation therapy (total 44 Gy) in the right bucco-gingival region for inflammatory pseudotumour was found\\u000a to have metachronous double malignant neoplasms. Initial osteosarcoma of the right mandibular angle and subsequent squamous\\u000a cell carcinoma of the right buccal mucosa were identified 28 and 33 years after the radiation, respectively. Since both tumours\\u000a were

K. Onodera; R. Ichinohasama; Kiyoshi Ooya



Gene expression profiling of epithelial ovarian tumours correlated with malignant potential  

PubMed Central

Background Epithelial ovarian tumours exhibit a range of malignant potential, presenting distinct clinical phenotypes. Improved knowledge of gene expression changes and functional pathways associated with these clinical phenotypes may lead to new treatment targets, markers for early detection and a better understanding of disease progression. Results Gene expression profiling (Affymetrix, U95Av2) was carried out on 18 ovarian tumours including benign adenomas, borderline adenocarcinomas of low malignant potential and malignant adenocarcinomas. Clustering the expression profiles of samples from patients not treated with chemotherapy prior to surgery effectively classified 92% of samples into their proper histopathological group. Some cancer samples from patients treated with chemotherapy prior to surgery clustered with the benign adenomas. Chemotherapy patients whose tumours exhibited benign-like expression patterns remained disease free for the duration of this study as indicated by continued normal serum CA-125 levels. Statistical analysis identified 163 differentially expressed genes: 61 genes under-expressed in cancer and 102 genes over-expressed in cancer. Profiling the functional categories of co-ordinately expressed genes within this list revealed significant correlation between increased malignant potential and loss of both IGF binding proteins and cell adhesion molecules. Interestingly, in several instances co-ordinately expressed genes sharing biological function also shared chromosomal location. Conclusion Our findings indicate that gene expression profiling can reliably distinguish between benign and malignant ovarian tumours. Expression profiles of samples from patients pre-treated with chemotherapy may be useful in predicting disease free survival and the likelihood of recurrence. Loss of expression of IGF binding proteins as well as specific cell adhesion molecules may be a significant mechanism of disease progression in ovarian cancer. Expression levels in borderline tumours were intermediate between benign adenomas and malignant adenocarcinomas for a significant portion of the differentially expressed genes, suggesting that borderline tumours are a transitional state between benign and malignant tumours. Finally, genes displaying coordinated changes in gene expression were often genetically linked, suggesting that changes in expression for these genes are the consequence of regional duplications, deletions or epigenetic events.

Warrenfeltz, Susanne; Pavlik, Stephen; Datta, Susmita; Kraemer, Eileen T; Benigno, Benedict; McDonald, John F



A multicentre study of fluconazole versus oral polyenes in the prevention of fungal infection in children with hematological or oncological malignancies  

Microsoft Academic Search

A randomized, comparative study was conducted in 502 patients in 23 centres worldwide to assess the efficacy and safety of fluconazole versus nystatin and amphotericin B for prevention of fungal infection in a severely immunocompromised pediatric population. Patients scheduled within 48 hours to undergo chemotherapy or radiotherapy for hematological or oncological malignancies were randomly allocated to receive 3 mg\\/kg oral

J. Ninane



Mapping of resection margins of oral cancer for p53 overexpression and chromosome instability to detect residual (pre)malignant cells  

Microsoft Academic Search

Oral squamous cell cancers (OSCCs) have a high local recurrence rate, partly due to problems in the recognition of minimal residual disease. The use of molecular markers is shown to increase the sensitivity of detection of residual malignant cells in tumour margins of OSCC. p53 immunohistochemistry was combined with in situ hybridization for chromosomes 1 and 7 to determine the

Peter-Paul G. van der Toorn; Joris A. Veltman; Fredrik J. Bot; Jong de Joseph M; Frans C. Ramaekers; Anton H. N. Hopman



Breast malignant phyllodes tumour metastasising to soft tissues of oral cavity  

Microsoft Academic Search

Metastases from infraclavicular neoplasms to the oral cavity are rare, and the anatomical structures most frequently affected\\u000a are the maxillae. The primary sites that develop metastases to head and neck include lung, breast, liver, thyroid gland, kidney\\u000a and melanomas, among others. The breast is one of the usual primary regions that can present them. In the literature, most\\u000a metastases to

M. de Lourdes Suárez Roa; L. M. Ruiz Godoy Rivera; T. Vela Chávez; M. Pérez Sánchez; A. Meneses García



Differential Inhibition of Protein Translation Machinery by Curcumin in Normal, Immortalized, and Malignant Oral Epithelial Cells  

Microsoft Academic Search

Curcumin has shown some promise in the prevention of oral carcinogenesis by mechanism(s) that are still not completely resolved. Messenger RNA translation is mediated in eukaryotes by the eIF4F complex composed of eukaryotic translation initiation factors eIF4E, eIF4G, and eIF4A. Overexpression of some of these components or the inactivation of initiation repressor proteins (4E-BP1) has been implicated in cancer development

Nitin Chakravarti; Humam Kadara; Do-Jun Yoon; Jerry W. Shay; Jeffrey N. Myers; Dafna Lotan; Nahum Sonenberg; Reuben Lotan



Standard examination and adjunctive techniques for detection of oral premalignant and malignant lesions.  


This article outlines how to perform a standard comprehensive extraoral and intraoral examination and the existing commercially available adjunctive techniques for the early detection of oral cancer and premalignant lesions. Visualization-based techniques (e.g., autofluorescence and chemiluminescence), toluidine blue vital staining, cytopathologic tests and high-risk human papillomavirus testing are discussed in detail, including the indications and protocols for use, their advantages and disadvantages and clinical cases. PMID:23795518

Kerr, A Ross; Shah, Sonal S



ALA-based fluorescent diagnosis of malignant oral lesions in the presence of bacterial porphyrin formation  

NASA Astrophysics Data System (ADS)

The aminolevulinic acid (5-ALA) -based fluorescence diagnosis has been found to be promising for an early detection and demarcation of superficial oral squamous cell carcinomas (OSCC). This method has previously demonstrated high sensitivity, however this clinical trial showed a specificity of approximately 62 %. This specificity was mainly restricted by tumor detection in the oral cavity in the presence of bacteria. After topical ALA application in the mouth of patients with previously diagnosed OSSC, red fluorescent areas were observed which did not correlate to confirm histological findings. Swabs and plaque samples were taken from 44 patients and cultivated microbiologically. Fluorescence was investigated (OMA-system) from 32 different bacteria strains found naturally in the oral cavity. After ALA incubation, 30 of 32 strains were found to synthesize fluorescent porphyrins, mainly Protoporphyrin IX. Also multiple fluorescent spectra were obtained having peak wavelengths of 636 nm and around 618 nm - 620 nm indicating synthesis of different porphyrins, such as the lipophylic Protoporphyrin IX (PpIX) and hydrophylic porphyrins (water soluble porphyrins, wsp). Of the 32 fluorescent bacterial strains, 18 produced wsp, often in combination with PpIX, and 5 produced solely wsp. These results clarify that ALA-based fluorescence diagnosis without consideration or suppression of bacteria fluorescence may lead to false-positive findings. It is necessary to suppress bacteria fluorescence with suitable antiseptics before starting the procedure. In this study, when specific antiseptic pre-treatment was performed bacterial associated fluorescence was significantly reduced.

Schleier, P.; Berndt, A.; Zinner, K.; Zenk, W.; Dietel, W.; Pfister, W.



Intraperitoneal VEGF inhibition using bevacizumab: a potential approach for the symptomatic treatment of malignant ascites?  


Despite overall improvements in oncological care in the palliative setting, symptomatic malignant ascites remains a severe clinical problem. This form of effusion is known to be widely resistant to established modes of systemic therapy. Accordingly, frequent paracentesis often represents the only effective way for symptom relief in patients with advanced cancer. This invasive mode of therapy, however, is often very burdensome for the patient who is already severely distressed by the underlying malignancy. Recently, the trifunctional monoclonal antibody catumaxomab given i.p. has shown symptom relief in patients with ovarian cancer and malignant ascites. On another front, the release of vascular endothelial growth factor (VEGF) by tumor cells has been identified as a main factor promoting the i.p. secretion of fluid. Accordingly, recent evidence suggests that targeting VEGF may have the potential to suspend the ascites production resulting from peritoneal metastasis. Here, we review preclinical and clinical data supporting this hypothesis. We show current evidence suggesting that the i.p. application of the anti-VEGF antibody bevacizumab, which is already in use as an i.v. therapeutic drug for a variety of tumors, might represent an effective way to prevent local fluid accumulation. Because such an effect would result in significant relief for patients, future clinical studies should stringently assess the effectiveness of this targeted therapy for the treatment of malignant i.p. effusions. PMID:20008305

Kobold, Sebastian; Hegewisch-Becker, Susanna; Oechsle, Karin; Jordan, Karin; Bokemeyer, Carsten; Atanackovic, Djordje



Diffuse reflectance spectroscopy: diagnostic accuracy of a non-invasive screening technique for early detection of malignant changes in the oral cavity  

PubMed Central

Background Strong proof-of-principle for utilisation of diffuse reflectance spectroscopy, a non-invasive tool for early detection of malignant changes, has emerged recently. The potential of this technique in distinguishing normal tissue from hyperplastic and dysplastic tissues was explored. Methods Diffuse reflectance (DR) spectra in the 400–700?nm region were obtained from the buccal mucosa of 96 patients and 34 healthy volunteers. The DR spectral data were compared against the gold standard biopsy and histopathology results. A principal-component analysis was performed for dimensional reduction in the normalised spectral data with linear discriminant analysis as the classifying technique. The receiver operator characteristic curve technique was employed for evaluating the performance of the diagnostic test. Results DR spectral features for different lesions, such as normal/healthy, hyperplastic, dysplastic and squamous cell carcinoma (SCC), varied significantly according to the intensity of oxygenated haemoglobin absorption. While the classification based on discriminant scores provided an overall sensitivity of 98.5% and specificity of 96.0% for distinguishing SCC from dysplasia, they were 100.0% and 95.0%, respectively, for distinguishing dysplasia from hyperplasia. Similarly, the analysis yielded a sensitivity of 95.0% and specificity of 100.0% for distinguishing hyperplasia from healthy tissue. The areas under the receiver operator characteristic curves were 0.98 (95% CI 0.95 to 1.00) and 0.95 (95% CI 0.90 to 1.00) for distinguishing dysplasia from SCC and hyperplasia from dysplasia, respectively. Conclusion DR spectral data efficiently discriminate healthy tissue from oral malignant lesions. Diagnostic accuracies obtained in this study highlight the potential use of this method for routine clinical practice.

Jayanthi, J L; Nisha, G U; Manju, S; Philip, E K; Jeemon, P; Baiju, K V; Beena, V T



In vitro assay of the invasive potential of malignant bone and soft tissue tumours through basement membranes  

Microsoft Academic Search

We have used reconstituted basement membrane molecules which have formed into barriers in order to investigate the invasive potential of malignant bone and soft tissue tumour cells in vitro. A number of cell lines established from human malignant tumours demonstrated a high degree of invasiveness, although fibroblasts showed no ability to penetrate the basement membrane barrier. H-ras oncogene transfected cells

Y. Iwamoto; K. Tanaka; K. Okuyama; Y. Sugioka; S. Taniguchi



Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value.  


Several recent studies have indicated that cells at the invasive tumour margins often are different from cells within other parts of various human cancers. In this work, we have studied all squamous cell carcinomas of the floor of the mouth registered in Norway during the years 1963-1972 (N = 96). Borderline cases and cases given no treatment were excluded. Of the remaining 79 cases, biopsy specimens acceptable for histological grading were obtained from 61 patients. Only the most invasive margins of the tumours were histologically graded independently by two pathologists according to a multifactorial grading system. The results confirmed our previous findings that grading of invasive tumour margins is an independent prognostic factor in Cox's multivariate survival analysis (P less than 0.01). Inter-observer agreement was calculated by kappa statistics, and good agreement was obtained (kappa = 0.63). Neither agreement nor prognostic value was improved after calibration of the pathologists. Conventional Borders' grading of the whole biopsy had no prognostic value (P less than 0.38). We conclude that invasive cell grading may be of value for treatment planning of oral cancers, and that further studies of the deep, invasive parts of oral and other cancers are needed in order to obtain a better understanding of tumour cell invasion and metastasis. PMID:1517891

Bryne, M; Koppang, H S; Lilleng, R; Kjaerheim, A



A Case control study to evaluate oxidative stress in plasma samples of oral malignancy  

PubMed Central

Background: Imbalances between the oxidant –antioxidant status have been implicated in the pathogenesis of several diseases, including cancer. Aim: The aim of this study was to evaluate the extent of lipid peroxidation and antioxidants in the venous blood samples of oral squamous cell carcinoma patients of different Clinicopathologic stages in comparison with the healthy controls. Setting and Design: A Case control study was designed in a hospital (Rajah Muthiah Dental College and Hospital, Annamalai University) based setting. Materials and Methods: Twenty new histopathologically proven oral carcinoma patients, and equal number of age, sex and habit matched healthy subjects were recruited for this study. Their blood samples were subjected to evaluation of Thiobarbituric Acid Reactive Substances (TBARS) and antioxidant enzymes, namely, superoxide dismutase (SOD), Catalase (CAT) reduced glutathione (GSH) and glutathione peroxidase (GPx) using spectrophotometric methods. Statistical Analysis: The data are expressed as mean±SD. The statistical comparisons were performed by independent Student's t-test and One Way ANOVA. P value <0.05 was considered statistically significant. Karl Pearson correlation was performed for the biochemical parameters within the group and between the groups. For statistically significant correlations, linear regression was performed. Results: Significant enhanced lipid peroxidation (P<0.001) with decrease in antioxidants (P<0.001) was observed in the venous blood of oral squamous cell carcinoma patients as compared with the healthy controls. Accordingly, significant (P<0.001) pattern of progression in TBARS levels was observed at various clinical stages of patients. (GSH) showed significant (P<0.01) negative correlation with TBARS and positive correlation (P<0.001) with SOD. On linear regression analysis, GSH showed significance for SOD (P<0.001), GPx, CAT and TBARS (P<0.01). It was also found that, 70% of variance in SOD can be attributed to the influence of GSH alone. Conclusion: Enhanced lipid peroxidation and compromised antioxidant defense in plasma indicate development of oxidative stress. Amongst the antioxidant enzymes, (GSH) appears to have a profound role in carcinogenesis.

Srivastava, Kumar Chandan; Austin, Ravi David; Shrivastava, Deepti; Sethupathy, S.; Rajesh, S.



Clinical effects of oral green tea extracts in four patients with low grade B-cell malignancies.  


Green tea or its constituents have long been touted as a health promoting substance including claims it may have cancer prevention properties. We previously reported the in vitro ability of one tea polyphenol, epigallocatechin gallate (EGCG), to induce apoptotic cell death in the leukemic B-cells from a majority of patients with chronic lymphocytic leukemia (CLL). After the publication of our findings many patients with CLL and other low grade lymphomas began using over-the-counter products containing tea polyphenols despite the absence of evidence to suggest clinical benefit, definition of possible toxicities, or information on optimal dose and schedule. We have become aware of four patients with low grade B-cell malignancies seen in our clinical practice at Mayo Clinic who began, on their own initiative, oral ingestion of EGCG containing products and subsequently appeared to have an objective clinical response. Three of these four patients met criteria for partial response (PR) by standard response criteria. Although spontaneous remission/regression is occasionally observed in individuals with low grade B-cell malignancies, such events are rare. Several patients presented here had documented steady clinical, laboratory, and/or radiographic evidence of progression immediately prior to initiation of over-the-counter green tea products and then developed objective responses shortly after self-initiating this therapy. Such anecdotes highlight the need for clinical trials of tea polyphenols to define the optimal dosing, schedule, toxicities, and clinical efficacy before widespread use can be recommended. An NCI sponsored phase I/II trial of de-caffeinated green tea extracts for patients with asymptomatic, early stage CLL opened at Mayo Clinic in August 2005. PMID:16325256

Shanafelt, T D; Lee, Y K; Call, T G; Nowakowski, G S; Dingli, D; Zent, C S; Kay, N E



Oral microbiota and cancer  

PubMed Central

Inflammation caused by infections may be the most important preventable cause of cancer in general. However, in the oral cavity the role of microbiota in carcinogenesis is not known. Microbial populations on mouth mucosa differ between healthy and malignant sites and certain oral bacterial species have been linked with malignancies but the evidence is still weak in this respect. Nevertheless, oral microorganisms inevitably up-regulate cytokines and other inflammatory mediators that affect the complex metabolic pathways and may thus be involved in carcinogenesis. Poor oral health associates statistically with prevalence of many types of cancer, such as pancreatic and gastrointestinal cancer. Furthermore, several oral micro-organisms are capable of converting alcohol to carcinogenic acetaldehyde which also may partly explain the known association between heavy drinking, smoking, poor oral health and the prevalence of oral and upper gastrointestinal cancer. A different problem is the cancer treatment-caused alterations in oral microbiota which may lead to the emergence of potential pathogens and subsequent other systemic health problems to the patients. Hence clinical guidelines and recommendations have been presented to control oral microbiota in patients with malignant disease, but also in this area the scientific evidence is weak. More controlled studies are needed for further conclusion.

Meurman, Jukka H.



Adiponectin and metformin additively attenuate IL1?-induced malignant potential of colon cancer.  


Both adiponectin (AD) and metformin (Met) have been proposed to downregulate cell proliferation of colon cancer cells, but whether their effect might be additive has not been studied to date. Genetic studies in humans have suggested an important role for interleukin 1? (IL1?) in cancer pathogenesis. Direct evidence that IL1? contributes to the development of colon cancer has not yet been fully confirmed and no previous studies have evaluated how IL1? may interact with AD and/or Met to regulate malignant potential and intracellular signaling pathways in human and mouse colon cancer cells. We conducted in vitro studies using human (LoVo) and mouse (MCA38) colon cancer cell lines to evaluate whether AD and Met alone or in combination may antagonize IL1?-regulated malignant potential in human and mouse colon cancer cell lines. IL1? increased malignant potential and regulated the expression of tumor suppressor (p53) and cell cycle regulatory genes (p21, p27, and cyclin E2) in human and mouse colon cancer cell lines. These effects were reversed by co-administration of AD and/or Met and were additively altered by AD and Met in combination in a STAT3- and AMPK/LKB1-dependent manner. We also observed using fluorescence activated cell sorter analysis that IL1?-regulated cell cycle progression is altered by AD and Met alone or in combination. Our novel mechanistic studies provide evidence for an important role for IL1? in colon cancer and suggest that AD and/or Met might be useful agents in the management or chemoprevention of IL1?-induced colon carcinogenesis. PMID:24157941

Moon, Hyun-Seuk; Mantzoros, Christos S



Remission of a chemotherapy resistant tumor of low malignant potential with tamoxifen.  


Low Malignant Potential (LMP) tumor of the ovary represents 15% of all ovarian tumors. The prognosis is excellent even in patients with extensive tumor involvement. However 20% of the patients die of disease in a 20 year period. Management of patients after surgery is not defined. Chemotherapy has shown response rates of 20% but no improvement in survival. Toxicity has been reported. We present a case of chemotherapy resistant LMP tumor with serologic response to tamoxifen, no evidence of disease and an excellent quality of life. Hormonal therapy may be considered in the treatment of LMP tumors. PMID:9061316

Llerena, E; Kudelka, A P; Tornos, C; Cedillo, G F; Lopez, A; Edwards, C L; Litam, J P; Kavanagh, J J



The potential of chitosan for the oral administration of peptides.  


Over recent years, a major challenge in drug delivery has been the design of appropriate vehicles for the oral administration of macromolecular drugs (peptides and proteins). Indeed, despite the increasing market value of these complex molecules, their clinical use has been highly limited by their reduced oral bioavailability. Among the different delivery approaches explored so far, those based on the use of the polysaccharide chitosan have opened promising alternatives towards this ambitious goal. This is due to the interesting physicochemical and biopharmaceutical properties of this polymer. This article describes the advances that have been made in the design of chitosan-based systems specially adapted for the oral administration of peptides. These systems include solutions, microspheres, nanoparticles, nanocapsules and liposomes. More specifically, this article discusses the efficacy of the different delivery approaches for improving the absorption of peptides, and analyses the various mechanisms that have been proposed for the understanding of their efficacy. PMID:16296782

Prego, Cecilia; Torres, Dolores; Alonso, Maria Jose



Mesothelioma of tunica vaginalis of "uncertain malignant potential" - an evolving concept: case report and review of the literature  

PubMed Central

Mesothelioma of tunica vaginalis is a rare neoplasm, typically demonstrating frankly malignant morphology and aggressive behavior. Rare cases of well-differentiated papillary mesotheliomas have also been reported, which, in contrast, demonstrate indolent behavior. There are, however, cases which do not fit into the well-differentiated or diffuse malignant mesothelioma categories and can be considered mesothelioma of tunica vaginalis of "uncertain malignant potential", which is an emerging diagnostic category. A 57-year-old man presented with a neoplasm in a hydrocele sac. The neoplasm was non-invasive, but showed focal complex and solid growth and it was difficult to categorize either as well-differentiated papillary mesotheliomas or malignant mesothelioma. After the initial limited resection, the patient underwent radical orchiectomy with hemiscrotectomy and is alive and without disease progression after 6 years. Documentation of these rare tumors will allow their distinction from true malignant mesotheliomas and will facilitate the development of specific treatment recommendations.



Precancerous stem cells have the potential for both benign and malignant differentiation.  


Cancer stem cells (CSCs) have been identified in hematopoietic and solid tumors. However, their precursors-namely, precancerous stem cells (pCSCs) -have not been characterized. Here we experimentally define the pCSCs that have the potential for both benign and malignant differentiation, depending on environmental cues. While clonal pCSCs can develop into various types of tissue cells in immunocompetent mice without developing into cancer, they often develop, however, into leukemic or solid cancers composed of various types of cancer cells in immunodeficient mice. The progress of the pCSCs to cancers is associated with the up-regulation of c-kit and Sca-1, as well as with lineage markers. Mechanistically, the pCSCs are regulated by the PIWI/AGO family gene called piwil2. Our results provide clear evidence that a single clone of pCSCs has the potential for both benign and malignant differentiation, depending on the environmental cues. We anticipate pCSCs to be a novel target for the early detection, prevention, and therapy of cancers. PMID:17356702

Chen, Li; Shen, Rulong; Ye, Yin; Pu, Xin-An; Liu, Xingluo; Duan, Wenrui; Wen, Jing; Zimmerer, Jason; Wang, Ying; Liu, Yan; Lasky, Larry C; Heerema, Nyla A; Perrotti, Danilo; Ozato, Keiko; Kuramochi-Miyagawa, Satomi; Nakano, Toru; Yates, Allen J; Carson, William E; Lin, Haifan; Barsky, Sanford H; Gao, Jian-Xin



PDZ Domains and Viral Infection: Versatile Potentials of HPV-PDZ Interactions in relation to Malignancy  

PubMed Central

Cervical cancer is caused by high-risk human papillomaviruses (HPVs), and a unique characteristic of these is a PDZ (P¯SD-95/D¯lg/Z¯O-1-)binding motif in their E6 proteins. Through this motif HPV E6 interacts with a variety of PDZ domain-containing proteins and targets them mainly for degradation. These E6-PDZ interactions exhibit extraordinarily different functions in relation to HPV-induced malignancy, depending upon various cellular contexts; for example, Dlg and Scrib show different distribution patterns from what is seen in normal epithelium, both in localization and in amount, and their loss may be a late-stage marker in malignant progression. Recent studies show that interactions with specific forms of the proteins may have oncogenic potential. In addition, it is interesting that PDZ proteins make a contribution to the stabilization of E6 and viral episomal maintenance during the course of HPV life cycle. Various posttranslational modifications also greatly affect their functions. Phosphorylation of hDlg and hScrib by certain kinases regulates several important signaling cascades, and E6-PDZ interactions themselves are regulated through PKA-dependent phosphorylation. Thus these interactions naturally have great potential for both predictive and therapeutic applications, and, with development of screening tools for identifying novel targets of their interactions, comprehensive spatiotemporal analysis is currently underway.

Kawana, Kei; Osuga, Yutaka; Fujii, Tomoyuki



Reduction of potential respiratory pathogens by oral hygienic treatment in patients undergoing endotracheal anesthesia  

Microsoft Academic Search

Purpose.?This study was conducted to evaluate the usefulness of mechanical and chemical prophylactic oral cleansing treatments for\\u000a reducing potential respiratory pathogens existing in the oral cavity.\\u000a \\u000a \\u000a \\u000a \\u000a Methods.?Thirty-two patients scheduled to undergo oral and maxillofacial surgery that required endotracheal anesthesia were randomly\\u000a allocated to one of the two groups, the oral cleansing group (n = 16) or the noncleansing group (n

Minori Okuda; Yuzuru Kaneko; Tatsuya Ichinohe; Kazuyuki Ishihara; Katsuji Okuda



Inhibitors of apoptosis proteins (IAPs) as potential molecular targets for therapy of hematological malignancies.  


Apoptosis, a programmed cell death, plays a key role in the regulation of tissue homeostasis. However, impairment of its regulation may promote formation and progression of malignancy. An important part of the apoptotic machinery are the inhibitor of apoptosis protein (IAP) family, regulating caspase activity, cell division or cell survival pathways through binding to their baculovirus AIP repeat (BIR) domains and/or by their ubiquitin-ligase RING zinc finger (RZF) activity. The following IAPs have been described so far: NAIP (neuronal apoptosis inhibitory protein; BIRC1), cIAP1 and cIAP2 (cellular inhibitor of apoptosis 1 and 2; BIRC2 and BIRC3, respectively), XIAP (X-chromosome binding IAP; BIRC4), survivin (BIRC5), BRUCE (Apollon; BIRC6), livin (BIRC7) and Ts-IAP (testis-specific IAP; BIRC8). Several studies suggested a potential contribution of IAPs to oncogenesis and resistance to anti-tumor treatment. Increased IAP expression was found in variety of human cancers, including hematological malignancies, such as leukemias and B-cell lymphomas. A correlation between the progression of those diseases and high levels of survivin or XIAP has been reported. Overexpression of XIAP in acute myeloid leukemia or survivin in acute lymphoblastic leukemia and diffuse large B-cell lymphoma have been indicated as an unfavorable prognostic factors. Elevated cellular levels of cIAP1, cIAP2, XIAP and survivin correlated with a progressive course of chronic lymphocytic leukemia. Thus, targeting IAPs with small-molecule inhibitors by their antisense approaches or natural IAP antagonist mimetics, may be an attractive strategy of anti-cancer treatment. Such agents can either directly induce apoptosis of tumor cells or sensitize them to other cytotoxic agents, hence overcoming drug-resistance. This review demonstrates the current knowledge on IAP molecular biology, as well as the mechanisms of action and the development of IAP-targeting agents for treatment of hematological malignancies. PMID:21902653

Smolewski, P; Robak, T



The probability of malignancy in small pulmonary nodules coexisting with potentially operable lung cancer detected by CT  

Microsoft Academic Search

The aim of this study was to assess the probability of malignancy in one or two small nodules 1 cm or less coexisting with\\u000a potentially operable lung cancer (coexisting small nodules). The preoperative helical CT scans of 223 patients with lung cancer\\u000a were retrospectively reviewed. The probability of malignancy of coexisting small nodules was evaluated based on nodule size,\\u000a location, and

Yue Yuan; Tsuneo Matsumoto; Atsuto Hiyama; Goji Miura; Nobuyuki Tanaka; Takuya Emoto; Takeo Kawamura; Naofumi Matsunaga



DNA methylation state of the galectin-3 gene represents a potential new marker of thyroid malignancy  

PubMed Central

In order to supplement the cytopathological assessment of thyroid tumors, there is a need for new markers to correctly diagnose malignant thyroid lesions and avoid unnecessary and potentially harmful therapies for patients. The immunohistochemical expression of galectin-3 is currently considered to be the most accurate stand-alone marker for thyroid cancer diagnosis. The aim of this study was to establish whether the methylation state of the galectin-3 gene is a candidate molecular marker for thyroid malignancy. Thyroid specimens from 50 patients were analyzed, including 5 normal thyroid, 3 goiters, 39 papillary and 3 anaplastic thyroid carcinoma cases. High-resolution methylation analyses was performed to investigate the methylation state of a large genomic region (from ?89 to +408) encompassing the galectin-3 transcriptional start site. Within this region, 5 CpG sites (nucleotide positions +134, +137, +142, +147 and +156) were observed to be differentially methylated among the samples and were further analyzed by the quantitative pyrosequencing technique. The hypomethylation of the +134, +137, +142, +147 and +156 CpG sites was observed to be markedly associated with cancer. Although the methylation degree of each single site was highly variable in non-neoplastic tissues, the average methylation state of the 5 CpG sites clearly distinguished cancer from the nonneoplastic thyroid tissues.




'Decoy' and 'non-decoy' functions of DcR3 promote malignant potential in human malignant fibrous histiocytoma cells  

PubMed Central

Decoy receptor 3 (DcR3) is a soluble secreted protein that belongs to the tumor necrosis factor receptor (TNFR) superfamily. DcR3 inhibits the Fas ligand (FasL)/Fas apoptotic pathway by binding to FasL, competitively with Fas receptor. Previous studies have reported that overexpression of DcR3 has been detected in various human malignancies and that DcR3 functions as a ‘decoy’ for FasL to inhibit FasL-induced apoptosis. In addition, recent studies have revealed that DcR3 has ‘non-decoy’ functions to promote tumor cell migration and invasion, suggesting that DcR3 may play important roles in tumor progression by decoy and non-decoy functions. We have previously reported that overexpression of DcR3 was observed in human malignant fibrous histiocytoma (MFH), however, the roles of DcR3 in MFH have not been studied. In the present study, to elucidate the roles of DcR3 in tumor progression of MFH, we examined the effects of DcR3 inhibition on cell apoptosis, migration and invasion in human MFH cells. siRNA knockdown of DcR3 enhanced the FasL-induced apoptotic activity and significantly decreased cell migration and invasion with a decrease in the activation of phosphatidylinositol 3 kinase (PI3K)/Akt and matrix metalloproteinase (MMP)-2. The findings in this study strongly suggest that DcR3 plays important roles in tumor progression of human MFH by decoy as well as non-decoy functions and that DcR3 may serve as a potent therapeutic target for human MFH.




Inhibition of transient receptor potential canonical channels impairs cytokinesis in human malignant gliomas  

PubMed Central

Objectives Glial-derived primary brain tumours, gliomas, are among the fastest growing malignancies and present a huge clinical challenge. Research suggests an important, yet poorly understood, role of ion channels in growth control of normal and malignant cells. In this study, we sought to functionally characterize Transient Receptor Potential Canoncial (TRPC) channels in glioma cell proliferation. TRPC channels form non-selective cation channels that have been suggested to represent a Ca2+ influx pathway impacting cellular growth. Materials and Methods Employing a combination of molecular, biochemical and biophysical techniques, we characterized TRPC channels in glioma cells. Results We showed consistent expression of four channel family members (TRPC-1, -3, -5, -6) in glioma cell lines and acute patient-derived tissues. These channels gave rise to small, non-voltage-dependent cation currents that were blocked by the TRPC inhibitors GdCl3, 2-APB, or SKF96365. Importantly, TRPC channels contributed to the resting conductance of glioma cells and their acute pharmacological inhibition caused an ~10 mV hyperpolarization of the cells’ resting potential. Additionally, chronic application of the TRPC inhibitor SKF96365 caused near complete growth arrest. A detailed analysis, by fluorescence-activated cell sorting and time-lapse microscopy, showed that growth inhibition occurred at the G2 + M phase of the cell cycle with cytokinesis defects. Cells underwent incomplete cell divisions and became multinucleate, enlarged cells. Conclusions Nuclear atypia and enlarged cells are histopathological hallmarks for glioblastoma multiforme, the highest grade glioma, suggesting that a defect in TRPC channel function may contribute to cellular abnormalities in these tumours.

Bomben, V. C.; Sontheimer, H. W.



Evaluation of an oral health scale of infectious potential using a telematic survey of visual diagnosis  

PubMed Central

Objective: To compare the results of a subjective estimation of oral health through review of a set of intraoral photographs with those of an objective oral health scale of infectious potential. Method: The pool of patients was made up of 100 adults. Using an infectious-potential scale based on dental and periodontal variables, we assigned 1 of the 4 grades of the scale (range, 0 to 3; 0 corresponds to an excellent oral health status and 3 to the poorest oral health status) to each subject. A total of 20 representative subjects were selected from the pool of patients, 5 subjects for each one of the grades of the scale, and a standardized photographic record was made. One thousand dentists practicing in Spain were sent the survey by e-mail and 174 completed forms were received. We then calculated the concordance of the oral health status indicated by the respondents after visualising the photographs on comparison with the results of the oral health scale of infectious potential; concordance was termed correct grade allocation (CGA). Results: The majority of respondents (69.1%) achieved a CGA in 8 to 12 cases and none achieved more than 15 CGAs. The poorest CGA rates were found with grades 1 and 2, with a mean of 1.74 ± 1.09 and 1.87 ± 1.18, respectively, out of a maximum of 5. The concordance in terms of CGA was high for grade 0 (70.5%), very low for grade 1 (10.8%), low for grade 2 (37.3%), and moderate for grade 3 (42.6%). Conclusion: In comparison with visual examination of the oral cavity, the use of objective scale that establishes a reliable diagnosis of oral health in terms of infectious potential was found to be advantageous. Key words:Diagnosis, intraoral photographies, oral health scale, objective estimation, visual examination.

Relvas, Marta; Limeres, Jacobo; Cabral, Cristina; Velazco, Corsina; Diz, Pedro



Clinical recommendations for oral cancer screening  

Microsoft Academic Search

Scope and purposeTo address the benefits and limitations of oral cancer screening and the use of adjunctive screening aids to visualise and detect potentially malignant and malignant oral lesions. Squamous cell carcinomas of the lips and cancers of the oropharynx (including the posterior one-third of the base of the tongue and the tonsils were excluded.MethodologyA specially convened expert panel evaluated

Derek Richards



Expression of growth differentiation factor 15 is positively correlated with histopathological malignant grade and in vitro cell proliferation in oral squamous cell carcinoma.  


Previously, we established an in vitro cellular carcinogenesis model of oral squamous cell carcinoma (OSCC) and expression microarray analysis showed that the gene encoding growth differentiation factor 15 (GDF15) was significantly upregulated in this model. In this study, we confirmed that expression of GDF15 was increased both at mRNA and protein levels in a panel of OSCC lines and clinical samples from primary OSCC patients. We also observed that expression of GDF15 was positively correlated with the malignancy of the disease: a higher level of GDF15 expression indicates a higher malignant grade of OSCC. Treatment of OSCC cell line (Tca3118) with siRNA against GDF15 significantly inhibited cellular proliferation and colony formation. Based on these observations, we conclude that GDF15 is a positive gene of OSCC development and progression and GDF15 can be used as an additional marker for histopathologic evaluation of OSCC differentiation. PMID:18805046

Zhang, Lei; Yang, Xiao; Pan, Hong-ya; Zhou, Xiao-jian; Li, Jiang; Chen, Wan-tao; Zhong, Lai-ping; Zhang, Zhi-yuan



DNA methylation profile of 28 potential marker loci in malignant mesothelioma  

PubMed Central

Summary Patients with malignant mesothelioma (MM), an aggressive cancer associated with asbestos exposure, usually present clinically with advanced disease and this greatly reduces the likelihood of curative treatment. MM is difficult to diagnose without invasive techniques; the development of non-invasively detectable molecular markers would therefore be highly beneficial. DNA methylation changes in cancer cells provide powerful markers that are potentially detectable non-invasively in DNA shed into bodily fluids. Here we examined the methylation status of 28 loci in 52 MM tumors to investigate their potential as molecular markers for MM. To exclude candidate MM markers that might be positive in biopsies/pleural fluid due to contaminating surrounding non-tumor lung tissue/DNA, we also examined the methylation of these markers in lung samples (age- or environmentally-induced hypermethylation is frequently observed in non-cancerous lung). Statistically significantly increased methylation in MM vs. non-tumor lung samples was found for estrogen receptor 1 (ESR1; p=0.0002), solute carrier family 6 member 20 (SLC6A20; p=0.0022) and spleen tyrosine kinase (SYK; p=0.0003). Examination of associations between methylation levels of the 28 loci and clinical parameters suggest associations of the methylation status of metallothionein genes with gender, histology, asbestos exposure, and lymph node involvement, and the methylation status of leucine zipper tumor suppressor 1 (LZTS1) and SLC6A20 with survival.

Tsou, Jeffrey A.; Galler, Janice S.; Wali, Anil; Ye, Wei; Siegmund, Kimberly D.; Groshen, Susan; Laird, Peter W.; Turla, Sally; Koss, Michael N.; Pass, Harvey I.; Laird-Offringa, Ite A.



Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells  

Microsoft Academic Search

An in vitro model for oral cancer was used to examine the growth inhibitory effects of chemopreventive agents when used singly and in combination. The model consists of primary cultures of normal oral epithelial cells, newly established cell lines derived from dysplastic leukoplakia and squamous cell carcinoma. Two naturally occurring substances, (-)-epigallocatechin-3-gallate (EGCG) from green tea and curcumin from the

Avi Khafif; Stimson P. Schantz; Ting-Chao Chou; David Edelstein; Peter G. Sacks


Anticancer property of bromelain with therapeutic potential in malignant peritoneal mesothelioma.  


Bromelain is a mixture of proteolytic enzymes that is capable of hydrolyzing glycosidic linkages in glycoprotein. Glycoprotein's are ubiquitously distributed throughout the body and serve a variety of physiologic functions. Faulty glycosylation of proteins may lead to cancer. Antitumor properties of bromelain have been demonstrated in both, in vitro and in vivo studies, along with scanty anecdotal human studies. Various mechanistic pathways have been proposed to explain the anticancer properties of bromelain. However, proteolysis by bromelain has been suggested as a main pathway by some researchers. MUC1 is a glycoprotein that provides tumor cells with invasive, metastatic, and chemo-resistant properties. To date, there is no study that examines the effect of bromelain on MUC1. However, the viability of MUC1 expressing pancreatic and breast cancer cells are adversely affected by bromelain. Further, the efficacy of cisplatin and 5-FU are enhanced by adjuvant treatment with bromelain, indicating that the barrier function of MUC1 may be affected. Other studies have also indicated that there is a greater accumulation of 5-FU in the cell compartment on treatment with 5-FU and bromelain. Malignant peritoneal mesothelioma (MPM) expresses MUC1 and initial studies have shown that the viability of MPM cells is adversely affected by exposure to bromelain. Further, bromelain in combination with either 5-FU or cisplatin, the efficacy of the chemotherapeutic drug is enhanced. Hence, current evidence indicates that bromelain may have the potential of being developed into an effective anticancer agent for MPM. PMID:23570457

Pillai, Krishna; Akhter, Javed; Chua, Terence C; Morris, David Lawson



Pralatrexate, a dihydrofolate reductase inhibitor for the potential treatment of several malignancies.  


Pralatrexate, a 10-deazaaminopterin derivative, is being developed by Allos Therapeutics Inc for the potential treatment of malignancies. The folate analog inhibits dihydrofolate reductase and was developed to overcome the limitations of the folate analog methotrexate. Compared with methotrexate in preclinical studies, pralatrexate demonstrated superior intracellular transport via the reduced folate carrier, and increased accumulation within cells by enhanced polyglutamylation. Preclinical studies in vitro and in models of B-cell lymphomas, T-cell lymphomas and NSCLC indicated that pralatrexate exhibited antitumor activity that was superior to the activity of other antifolates. In phase I clinical trials, the DLT for pralatrexate was mucositis, which could be abrogated with folic acid and vitamin B12 supplementation. The administration of pralatrexate to patients with T-cell lymphomas and NSCLC resulted in significant tumor remissions. At the time of publication, pralatrexate was in phase II clinical trials for the treatment of peripheral T-cell lymphoma, a phase I/II trial in combination with gemcitabine for the treatment of non-Hodgkin's lymphoma, and a phase IIb trial in comparison with erlotinib in patients with NSCLC. Because of the limited therapies available for peripheral T-cell lymphoma, pralatrexate could have a secure niche for the treatment of this indication, if ongoing clinical trials and future phase III trials confirm the efficacy of the drug. In contrast, for pralatrexate to be incorporated into the accepted treatment options for NSCLC, the drug will need to prove clear superiority to established agents. PMID:18600598

Molina, Julian R



Reversible phosphorylation in haematological malignancies: potential role for protein tyrosine phosphatases in treatment?  


Most aspects of leukocyte physiology are under the control of reversible tyrosine phosphorylation. It is clear that excessive phosphorylation of signal transduction elements is a pivotal element of many different pathologies including haematological malignancies and accordingly, strategies that target such phosphorylation have clinically been proven highly successful for treatment of multiple types of leukemias and lymphomas. Cellular phosphorylation status is dependent on the resultant activity of kinases and phosphatases. The cell biology of the former is now well understood; for most cellular phosphoproteins we now know the kinases responsible for their phosphorylation and we understand the principles of their aberrant activity in disease. With respect to phosphatases, however, our knowledge is much patchier. Although the sequences of whole genomes allow us to identify phosphatases using in silico methodology, whereas transcription profiling allows us to understand how phosphatase expression is regulated during disease, most functional questions as to substrate specificity, dynamic regulation of phosphatase activity and potential for therapeutic intervention are still to a large degree open. Nevertheless, recent studies have allowed us to make meaningful statements on the role of tyrosine phosphatase activity in the three major signaling pathways that are commonly affected in leukemias, i.e. the Ras-Raf-ERK1/2, the Jak-STAT and the PI3K-PKB-mTOR pathways. Lessons learned from these pathways may well be applicable elsewhere in leukocyte biology as well. PMID:20659529

Ruela-de-Sousa, Roberta R; Queiroz, Karla C S; Peppelenbosch, Maikel P; Fuhler, Gwenny M



Investigation of ovarian neoplasia of low malignant potential for human papillomavirus.  


Recent in situ hybridization studies have suggested the presence of human papillomavirus type 6 (HPV-6) DNA in ovarian cancer cells. An association between HPV and ovarian neoplasia of low malignant potential (LMP) has not been previously identified. Paraffin-embedded tissue blocks from 24 patients with LMP ovarian tumors were screened for human papillomavirus DNA. The patients ranged in age from 18 to 73 years. Corresponding microscopic slides from each tissue block were reviewed to confirm the histopathologic diagnosis. For identification of HPV genome, deparaffinized sections were subjected to the polymerase chain reaction to achieve amplification of DNAs of HPV types 6, 11, 16, and 18. For each HPV type, a 120-base-pair region of the E6 gene was targeted for amplification. Human papillomaviral DNA was not detected in the tissue specimens subjected to polymerase chain reaction. These results suggest that HPV types 6, 11, 16, and 18 are not likely to play a role in LMP ovarian tumors. These results do not totally exclude possible contributions of other HPV types. PMID:2172118

McLellan, R; Buscema, J; Guerrero, E; Shah, K V; Woodruff, J D; Currie, J L



Could interleukin-15 potentiate histone deacetylase inhibitor effects in haematological malignancy?  


Despite significant progress in cancer therapy, prognosis in acute leukaemia remains dismal, and the development of new therapies is urgently warranted: in acute myeloid leukaemia, the current cure rate is of 30-40% in younger and much less in older patients. Chromatin remodeling through histone acetylation is one of the major mechanisms of transcriptional control of genes, and is involved in 'gene silencing' of antioncogenes in various tumour cells. Chromatin remodeling is also involved in transcriptional control of other genes, such as NKG2D ligand genes. Histone deacetylases and acetyltransferases are involved in the epigenetic regulation of gene expression, and increased/decreased activity of histone deacetylases has been reported in several cancer types. Histone deacetylase inhibitors were reportedly active in many cancers including hematological malignancies, and have been shown in numerous experiments to reduce cancer cell growth and enhance cell differentiation, growth arrest and apoptosis. In acute myeloid leukaemia, histone deacetylase inhibitors alone had limited efficacy, but their combination with other anticancer agents yielded promising results. Interleukin (IL)-15 is regarded with great hope in the immunotherapy of cancer, and IL-15-activated cytokine-induced killer cells showed potent antileukemic activity both in vitro and in vivo. IL-15 increases expression of NKG2D and its ligands and can increase natural killer cell mediated cytotoxicity against tumour cells. The administration of IL-15 was recently shown to be safe in preclinical models, and there are ongoing clinical trials of IL-15 in patients with cancer and HIV infection. We hypothesise that IL-15 will synergise with histone deacetylase inhibitors in increasing the levels of activatory NKG2D receptors on natural killer and CD8(+) T cells and of their ligands, the MHC class I related molecule A and B, on tumor cells, and will enhance innate immune antitumour responses in acute myeloid leukaemia and other haematological malignancies. Up-regulation of NKG2D-NKG2D-ligand antitumour immune response by combining histone deacetylase inhibitors with IL-15 has the potential to improve the efficacy of acute myeloid leukaemia treatment. PMID:23669372

Zdrenghea, Mihnea T



Comparative clinical study of the anti-emetic effects of oral ramosetron and injected granisetron in patients with malignant glioma undergoing ACNU chemotherapy.  


The effectiveness of ramosetron tablets and granisetron injection was compared for reducing the frequency of nausea, vomiting, and anorexia in patients with malignant glioma undergoing ACNU chemotherapy. Patients with malignant glioma to be treated with ACNU chemotherapy were randomly assigned to receive oral ramosetron (20 patients) or intravenous granisetron (19 patients) prior to ACNU injection. Gastrointestinal toxicity within 48 hours of ACNU injection was compared to that in patients who had received ACNU chemotherapy with dopamine D2 receptor-blocker as a historical control group. Within 24 hours of the administration of ACNU, 15 of the 20 patients treated with ramosetron and 16 of the 19 treated with granisetron were nausea-free, and 14 of the former and 14 of the latter regained their normal appetite. There was no significant difference in the anti-emetic effects. Ten of the 17 controls experienced no vomiting within 6 hours of the injection of ACNU, five were nausea-free within 24 hours, and two retained their normal appetite within 24 hours. Oral ramosetron has the same anti-anorectic and anti-emetic effects as intravenous granisetron. Ramosetron tablets are less expensive and are easy to take, so should be on the list of first-choice anti-emetic drugs for patients treated with ACNU chemotherapy. PMID:15973062

Yano, Shigetoshi; Makino, Keishi; Nakamura, Hideo; Kai, Yutaka; Morioka, Motohiro; Hamada, Jun-Ichiro; Kochi, Masato; Kuratsu, Jun-Ichi



Potentiation of oral anticoagulation and hemarthrosis associated with nabumetone.  


Concomitant therapy with warfarin and nonsteroidal antiinflammatory drugs (NSAIDs) is of concern due to the potential for increased bleeding. Nonsteroidal antiinflammatory drugs may alter patient response to warfarin by pharmacodynamic or pharmacokinetic interactions. A man receiving long-term, stable warfarin therapy experienced a significant increase in international normalized ratio 1 week after nabumetone was added to his regimen. Despite prompt reduction of the warfarin dosage, he experienced hemarthrosis of his right knee. Previous reports suggested lack of interaction between nabumetone and warfarin. Caution and close monitoring are advisable when the two agents are administered concomitantly. PMID:10678303

Dennis, V C; Thomas, B K; Hanlon, J E



Oral microbial heat-shock proteins and their potential contributions to infections.  


The oral cavity is a complex ecosystem in which several hundred microbial species normally cohabit harmoniously. However, under certain special conditions, the growth of some micro-organisms with a pathogenic potential is promoted, leading to infections such as dental caries, periodontal disease, and stomatitis. The physiology and pathogenic properties of micro-organisms are influenced by modifications in environmental conditions that lead to the synthesis of specific proteins known as the heat-shock proteins (HSPs). HSPs are families of highly conserved proteins whose main role is to allow micro-organisms to survive under stress conditions. HSPs act as molecular chaperones in the assembly and folding of proteins, and as proteases when damaged or toxic proteins have to be degraded. Several pathological functions have been associated with these proteins. Many HSPs of oral micro-organisms, particularly periodontopathogens, have been identified, and some of their properties-including location, cytotoxicity, and amino acid sequence homology with other HSPs-have been reported. Since these proteins are immunodominant antigens in many human pathogens, studies have recently focused on the potential contributions of HSPs to oral diseases. The cytotoxicity of some bacterial HSPs may contribute to tissue destruction, whereas the presence of common epitopes in host proteins and microbial HSPs may lead to autoimmune responses. Here, we review the current knowledge regarding HSPs produced by oral micro-organisms and discuss their possible contributions to the pathogenesis of oral infections. PMID:14656896

Goulhen, Florence; Grenier, Daniel; Mayrand, Denis



Study of feline oral squamous cell carcinoma: Potential target for cyclooxygenase inhibitor treatment  

Microsoft Academic Search

Oral squamous cell carcinoma (OSCC) is associated with high morbidity and mortality. A potential target for OSCC treatment is cyclooxygenase-2 (cox-2). Pet cats with naturally occurring OSCC may offer the opportunity to study anticancer activity of cox inhibitors. Cox-2 expression in feline OSCC was determined by immunohistochemistry. High intensity cox-2 immunoreactivity was detected in 6 of 34 (18%) feline OSCC

Lisa DiBernardi; Monique Doré; John A. Davis; Jane G. Owens; Sulma I. Mohammed; Carolyn F. Guptill; Deborah W. Knapp



Lymphatic invasion predicts aggressive behavior in melanocytic tumors of uncertain malignant potential (MELTUMP).  


Lymphatic invasion (LI) identified by immunohistochemical (IHC) staining is common in primary cutaneous melanoma, and LI has been shown to be an independent prognostic factor in melanoma. Its prognostic significance in melanocytic tumors of uncertain malignant potential (MELTUMPs) has not been well characterized. This study included 32 patients with provisional diagnoses of MELTUMP. Lesions were evaluated for tumor thickness, the presence of ulceration, mitotic figures, mitotic figures at the base, tumor infiltrating lymphocytes, as well as peritumoral and intratumoral lymphatic density. Dual IHC staining was used to microscopically detect lymphatic endothelium (podoplanin) containing melanoma cells (S100), with the aid of multispectral imaging in select cases. Univariate analysis was performed to identify associations between clinical and pathologic variables and melanoma-related events. The 32 patients had a median follow-up of 111 months. Two patients subsequently died of melanoma-related disease, 1 died of unknown causes, 5 developed nodal metastases, and the remainder showed no evidence of progressive disease. LI was identified in 8/32 patients (25%) by dual IHC staining, which included the 2 patients who died of melanoma-related disease, 1 patient with bulky nodal metastasis, 1/4 patients with microscopic nodal metastases, and 4 patients who showed no evidence of progressive disease. The presence of LI was associated with melanoma metastases or melanoma-related death (P=0.05). The presence of LI by dual IHC in MELTUMPs is associated with a poorer prognosis, specifically with melanoma metastasis, and may therefore serve as a useful prognostic factor for risk stratification of patients with these diagnostically challenging lesions. PMID:23552384

Abraham, Ronnie M; Karakousis, Giorgos; Acs, Geza; Ziober, Amy F; Cerroni, Lorenzo; Mihm, Martin C; Elder, David E; Xu, Xiaowei



The Continuum of Serous Ovarian Tumors of Low Malignant Potential and Low-Grade Serous Carcinoma of the Ovary  

Microsoft Academic Search

\\u000a Serous tumors of low malignant potential (LMP) and low-grade serous carcinomas appear to exist on a continuum. Factors that\\u000a increase the risk of relapse of serous tumors of LMP include stage (presence of peritoneal implants), type of peritoneal implant\\u000a (noninvasive or invasive), and the micropapillary pattern. Of serous tumors of LMP that recur, approximately 80% do so as\\u000a low-grade serous

David M. Gershenson


Potential of Dual Time Point FDG-PET Imaging in Differentiating Malignant from Benign Pleural Disease  

Microsoft Academic Search

Aim  The aim of this study was to assess the utility of dual time point 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) imaging in differentiating benign from malignant pleural disease.\\u000a \\u000a \\u000a \\u000a Methods  Fifty-five consecutive patients of suspected malignant pleural mesothelioma (MPM) and recurrence of MPM who were referred\\u000a for the evaluation underwent two sequential 18F-FDG-PET scans (dual time point imaging). The average percent change in

Ayse Mavi; Sandip Basu; Tevfik F. Cermik; Muammer Urhan; Mehdi Bathaii; Dhurairaj Thiruvenkatasamy; Mohamed Houseni; Simin Dadparvar; Abass Alavi



Oral squamous cell carcinoma proliferative phenotype is modulated by proanthocyanidins: a potential prevention and treatment alternative for oral cancer  

PubMed Central

Background Despite the recently reported drop in the overall death rate from cancer, the estimated survival rate and number of deaths from oral cancer remain virtually unchanged. Early detection efforts, in combination with strategies for prevention and risk-reduction, have the potential to dramatically improve clinical outcomes. The identification of non-toxic, effective treatments, including complementary and alternative therapies, is critical if the survival rate is to be improved. Epidemiologic studies have suggested a protective effect from certain plant-derived foods and extracts; however, it has been difficult to isolate and identify the compounds most responsible for these observations. The primary purpose of this study was to investigate the response of human oral squamous cell carcinoma (OSCC) to proanthocyanidin (PAC), a plant-derived compound that may inhibit the progression of several other cancers. Methods Using a series of in vitro assays, we sought to quantify the effects of PAC on OSCC, cervical carcinoma, and non-cancerous cell lines, specifically the effects of PAC on cell proliferation. Recent data suggest that infection with the human papillomavirus (HPV) may also modulate the proliferative potential of OSCC; therefore, we also measured the effects of PAC administration on HPV-transfected OSCC proliferation. Results Our results demonstrated that PAC administration was sufficient to significantly suppress cellular proliferation of OSCC in a dose-dependent manner. In addition, the increased proliferation of OSCC after transfection with HPV 16 was reduced by the administration of PAC, as was the proliferation of the cervical cancer and non-cancerous cell lines tested. Our results also provide preliminary evidence that PAC administration may induce apoptosis in cervical and oral cancer cell lines, while acting merely to suppress proliferation of the normal cell line control. Conclusion These results signify that PAC may be a compelling candidate for testing in both animal and human models. Furthermore, these data provide adequate justification for elucidating the divergent mechanisms of PAC-induced proliferation, inhibition, and apoptosis among these and other cell lines.

King, Michael; Chatelain, Kourt; Farris, Dustin; Jensen, Dayne; Pickup, Jason; Swapp, Aaron; O'Malley, Susan; Kingsley, Karl



Fluorine-18-labeled boronophenylalanine positron emission tomography for oral cancers: Qualitative and quantitative analyses of malignant tumors and normal structures in oral and maxillofacial regions  

PubMed Central

The present study aimed to demonstrate the features of fluorine-18-labeled boronophenylalanine positron emission tomography (18F-BPA-PET) to reveal oral cancer, as well as normal structures in the oral and maxillofacial regions. We analyzed 18F-BPA-PET findings from 8 patients with histologically confirmed recurrent and/or advanced oral cancer scheduled for boron neutron capture therapy. The capacity of 18F-BPA-PET to delineate tumor and normal structures was assessed qualitatively and quantitatively. Tumors were easily identified as high uptake areas in all cases. Although the eyes, which were depicted as a low uptake area, and tongue musculature were readily identified, major vessels were not noted in any of the cases. Areas corresponding to the surface of the dorsum tongue to middle pharynx were expressed as high uptake areas in all of the cases. Quantitatively, tumors were expressed as the highest uptake area in 6 of the 8 cases, while the dorsum tongue had the highest uptake area in the remaining 2 cases. 18F-BPA-PET is useful in demonstrating the presence of a tumor. Thus, it is crucial to note the presence of a high uptake area corresponding to the dorsum area of the tongue when diagnosing a tumor using this technique.




Esophagobronchial fistulae: Diagnosis by MDCT with oral contrast swallow examination of a benign and a malignant cause  

PubMed Central

We report two cases of esophagobronchial fistulae diagnosed by Multi-detector computed tomography (MDCT) oral contrast swallow examination. It is helpful to supplement the CT study with an oral contrast swallow as it aids in confirmation of a suspected fistula and also demonstrates the fistula tract better. We present the clinical details and the imaging findings on MDCT of two cases of esophagobronchial fistulae – one secondary to chronic chest tuberculosis and the other secondary to a squamous cell carcinoma of the upper esophagus – followed by discussion of the etiology, pathogenesis, and imaging of these fistulae.

Hegde, Rahul G; Kalekar, Tushar M; Gajbhiye, Meenakshi I; Bandgar, Amol S; Pawar, Shephali S; Khadse, Gopal J



Pegylated-liposomal doxorubicin and oral topotecan in eight children with relapsed high-grade malignant brain tumors  

Microsoft Academic Search

Background: The combination of topoisomerase I and II chemotherapeutic agents has shown promising preclinical synergistic effects in\\u000a the treatment of high-grade malignant brain tumors such as high-grade gliomas and choroid plexus carcinomas. To confirm the\\u000a effectiveness of this treatment combination and determine its possible toxicity, we conducted a retrospective review of the\\u000a charts of children who received the therapy. Methods:

Sabine Wagner; Ove Peters; Christin Fels; Gisela Janssen; Anne-Kathrin Liebeskind; Axel Sauerbrey; Meinolf Suttorp; Peter Hau; Johannes E. A. Wolff



Reversible phosphorylation in haematological malignancies: Potential role for protein tyrosine phosphatases in treatment?  

Microsoft Academic Search

Most aspects of leukocyte physiology are under the control of reversible tyrosine phosphorylation. It is clear that excessive phosphorylation of signal transduction elements is a pivotal element of many different pathologies including haematological malignancies and accordingly, strategies that target such phosphorylation have clinically been proven highly successful for treatment of multiple types of leukemias and lymphomas. Cellular phosphorylation status is

Roberta R. Ruela-de-Sousa; Karla C. S. Queiroz; Maikel P. Peppelenbosch; Gwenny M. Fuhler



Paraneoplastic alterartions of redox-potential of intact tissues in laboratory mice with spontaneous malignant tumors  

Microsoft Academic Search

Have been investigated electronic-paramagnetic signals of blood, skeletal muscle and liver tissue of laboratory mice with spontaneous malignant tumors (weight range 20-25 g.) with the use of electronic-paramagnetic resonance (EPR) method; also, activity of antioxidant enzyme catalase - by the method of H. Aebi and ceruloplasmin concentration in the blood serum - by the method of N. Babenko. Have been

Ketevan Gambashidze; Nino Bejitashvili; Tinatin Azaladze


The acquisition of malignant potential in colon cancer is regulated by the stabilization of Atonal homolog 1 protein.  


The transcription factor Atonal homolog 1 (Atoh1) plays crucial roles in the differentiation of intestinal epithelium cells. Although we have reported that the Atoh1 protein was degraded in colon cancer by aberrant Wnt signaling, a recent study has indicated that the Atoh1 protein is expressed in mucinous colon cancer (MC) and signet ring cell carcinoma (SRCC). However, the roles of the Atoh1 protein in MC are unknown. To mimic MC, a mutated Atoh1 protein was stably expressed in undifferentiated colon cancer cells. Microarray analysis revealed the acquisition of not only the differentiated cell form, but also malignant potential by Atoh1 protein stabilization. In particular, Atoh1 enhanced Wnt signaling, resulting in the induction of Lgr5 as a representative stem cell marker with the enrichment of cancer stem cells. Moreover, the fluorescent ubiquitination-based cell cycle indicator system with time-lapse live imaging demonstrated cell cycle arrest in the G0/G1 phase by Atoh1 protein stabilization. In conclusion, the Atoh1 protein regulates malignant potential rather than the differentiation phenotype of MC, suggesting the mechanism by which MC and SRCC are more malignant than non-mucinous adenocarcinoma. PMID:23333391

Kano, Yoshihito; Tsuchiya, Kiichiro; Zheng, Xiu; Horita, Nobukatsu; Fukushima, Keita; Hibiya, Shuji; Yamauchi, Yuhki; Nishimura, Tatsunori; Hinohara, Kunihiko; Gotoh, Noriko; Suzuki, Shinji; Okamoto, Ryuichi; Nakamura, Tetsuya; Watanabe, Mamoru



Coexpression of colligin and collagen in oral submucous fibrosis: plausible role in pathogenesis  

Microsoft Academic Search

The high incidence of oral submucous fibrosis (OSF), a potentially malignant condition of the oral cavity, in the Indian subcontinent is causally associated with commonly prevailing habit of chewing areca nut and tobacco. Knowledge of molecular alterations in OSF is meagre. OSF is characterised by progressive accumulation of collagen fibres in lamina propria and oral submucosa. Colligin\\/HSP47 is a 47KDa

J Kaur; M Rao; N Chakravarti; M Mathur; N. K Shukla; B. D Sanwal; R Ralhan



[Expression of sex hormones receptors in leiomyoma with uncertain potential of malignancy and endometrial leiomyosarcoma: differentiatial diagnosis and prognostic significance].  


A retrospective evaluation of progesterone (PR) and alpha-estrogen (ER) expression was carried out in 16 patients with smooth muscle tumors with uncertain potential of malignancy (STUMP) and 76 patients with uterine leiomyosarcoma (ULMS). PR expression was observed in 100% of intact myometrium and leiomyoma samples, while ER was expressed only in 37.1 +/- 4.2% and 23.5 +/- 4.1% of samples. In STUMP samples PR expression was observed in 66.7 +/- 11.7% of cases, in ULMS samples in 50.5 +/- 5.7% of cases. However, there was an inverse correlation between malignancy grade and sex hormones expression, although the number of positive cells and staining intensity didn't prove to be independent risk factors. The patients with ULMS G1 and STUMP expressing sex hormones have favorable prognosis, while negative receptor status of STUMP tumors is the marker of the worse prognosis. PMID:22416391

Abdalian, A M; Bobrov, I P; Klimachev, V V; Chechulin, M N; Lazarev, A F



Oral N-isopropyl-p-(I-123) iodoamphetamine (IMP): A potential marker for enterohepatic absorption studies  

SciTech Connect

While gastrointestinal transit studies using non-absorbable labels are now widely used, gastrointestinal studies with absorbable tracers potentially could describe both transit and absorption. To investigate this possibility, 27 fasting rats were given 100 I-123 IMP by gastric gavage and sacrificed at intervals ranging from 5 minutes to 12 hours later. Organ counts were obtained after dissection with a well counter and pre-dissection images were obtained with a gamma camera using a 512 x 512 imaging format. The percent of total body activity in various organs as a function of time was calculated. The results indicate a rapid clearance of activity from the stomach with subsequent uptake and clearance from the liver. Control studies (n=5) with orally administered 111-In-DTPA showed no significant liver accumulation. The results indicate oral IMP is thus potentially useful for quantification of gastric transit and enterohepatic absorption studies.

Pan, Z.Y.; Hawkins, R.A.; Bennett, L.R.; Yee, C.A.



Estrogen metabolism and the malignant potential of human papillomavirus immortalized keratinocytes.  


Increased 16alpha-hydroxylation of estradiol has been shown to be associated with heightened cancer risk in estrogen responsive tissue. Certain types of human papillomavirus (HPV) are cofactors for cancer in the cervix, an estrogen sensitive tissue. We have demonstrated that estradiol and 16alpha-hydroxyestrone increased the number of cells positive for proliferating cell nuclear antigen in HPV immortalized keratinocytes, the in vitro correlate of the premalignant keratinocyte. These estrogens caused the abnormal proliferation and anchorage independent growth, which correlates with malignant conversion. Indole-3-carbinol, a phytochemical in cruciferous vegetables known to preferentially induce 2-hydroxylation with minimal effect on 16alpha-hydroxylation, markedly blocked the ability of estradiol to increase anchorage independent growth. The results indicate that 16alpha-hydroxyestrone increases the malignant phenotype of HPV immortalized keratinocytes. However, indole-3-carbinol will block this response. PMID:9492342

Newfield, L; Bradlow, H L; Sepkovic, D W; Auborn, K



Phase I Study of JM216 (an Oral Platinum Analogue) in Combination with Paclitaxel in Patients with Advanced Malignancies  

Microsoft Academic Search

This phase I study wasconducted to determine the dose limitingtoxicity, maximum tolerated doses, andrecommended phase II doses of thecombination of JM-216 and paclitaxel. Patients received paclitaxel intravenouslyover one hour on day 1 of each cycle. OralJM-216 was administered on days 1–5starting after the paclitaxel infusion. Cycles were repeated every 21 days. Patients were accrued at nine differentdosing combinations. JM-216 doses

Suzanne Jones; John Hainsworth; Howard A. Burris; Dana Thompson; Eric Raefsky; Valerie Johnson; Sharon Calvert; Cecile Bulanhagui; David Lebwohl; F. Anthony Greco



Galectin-3 as a Potential Therapeutic Target in Tumors Arising from Malignant Endothelia  

Microsoft Academic Search

Angiosarcoma (ASA) in humans and hemangiosarcoma (HSA) in dogs are deadly neoplastic diseases charac- terized by an aggressive growth of malignant cells with endothelial phenotype, widespread metastasis, and poor response to chemotherapy. Galectin-3 (Gal-3), a B-galactoside-binding lectin implicated in tumor pro- gression and metastasis, endothelial cell biology and angiogenesis, and regulation of apoptosis and neo- plastic cell response to cytotoxic

Kim D. Johnson; Olga V. Glinskii; Valeri V. Mossineb; James R. Turk; Thomas P. Mawhinneyb; Douglas C. Anthony; Carolyn J. Henry; Virginia H. Huxley; Gennadi V. Glinsky; Kenneth J. Pienta; Avraham Raz; Vladislav V. Glinsky



Efficacy and safety of oral tapentadol extended release in Japanese and Korean patients with moderate to severe, chronic malignant tumor-related pain.  


Abstract Objective: This phase 3 study evaluated the efficacy and safety of tapentadol extended release (ER) compared with oxycodone controlled release (CR) for the management of moderate to severe, chronic malignant tumor-related cancer pain. Research design and methods: This randomized, double-blind, active-controlled study included Japanese and Korean patients with moderate to severe, chronic malignant tumor-related pain. Patients were randomized (1:1) to receive oral tapentadol ER (25-200?mg bid) or oral oxycodone HCl CR (5-40?mg bid) for 4 weeks of double-blind treatment. identifier: NCT01165281. Main outcome measures: This study was designed to evaluate the non-inferiority of the efficacy provided by tapentadol ER versus oxycodone CR, based on the mean change in average pain intensity (11 point numerical rating scale) from baseline to the last 3 days of study drug administration. Treatment-emergent adverse events (TEAEs) were recorded throughout the study. Results: Of the 374 patients who were screened, 343 were randomized and 236 completed treatment. The least-squares mean difference in the change in pain intensity from baseline to the last 3 days of study treatment between tapentadol ER and oxycodone CR was -0.06 (95% confidence interval [CI], -0.506 to 0.383). The upper limit of the 95% CI was <1 (the predefined threshold value for non-inferiority), indicating that tapentadol ER provided analgesic efficacy that was non-inferior to that of oxycodone CR. The percentage of patients reporting at least one TEAE was similar in the tapentadol ER (87.5% [147/168]) and oxycodone CR (90.1% [155/172]) treatment groups, but the incidence of gastrointestinal TEAEs was lower in the tapentadol ER group (55.4% [93/168]) than in the oxycodone CR group (67.4% [116/172]). Conclusions: Tapentadol ER (25-200?mg bid) provides analgesic efficacy that is non-inferior to that provided by oxycodone HCl CR (5-40?mg bid) for the management of moderate to severe, chronic malignant tumor-related pain, and is well tolerated overall, with a better gastrointestinal tolerability profile than oxycodone CR. PMID:23937387

Imanaka, Keiichiro; Tominaga, Yushin; Etropolski, Mila; van Hove, Ilse; Ohsaka, Masaki; Wanibe, Mikio; Hirose, Keiichiro; Matsumura, Taka



Determination of cytokine protein levels in oral secretions in patients undergoing radiotherapy for head and neck malignancies  

PubMed Central

Background Cytokines may be elevated in tumor and normal tissues following irradiation. Cytokine expression in these tissues may predict for toxicity or tumor control. The purpose of this pilot study was to determine the feasibility of measuring local salivary cytokine levels using buccal sponges in patients receiving chemo-radiation for head and neck malignancies. Patients and methods 11 patients with epithelial malignancies of the head and neck were recruiting to this study. All patients received radiotherapy to the head and neck region with doses ranging between 60 – 67.5?Gy. Chemotherapy was delivered concurrently with radiation in all patients. Salivary samples were obtained from high dose and low dose regions prior to treatment and at three intervals during treatment for assessment of cytokine levels (IL-4, IL-6, IL-8, IL-10, EGF, MCP-1, TNF-?, and VEGF). Results Cytokine levels were detectable in the salivary samples. Salivary cytokine levels of IL-4, IL-6, IL-8, EGF, MCP-1, TNF- ? , and VEGF were higher in the high dose region compared to the low dose region at all time points (p?



Goats are a potential reservoir for the herpesvirus (MCFV-WTD), causing malignant catarrhal fever in deer.  


In the recent investigation of malignant catarrhal fever in a red brocket deer (Mazama americana) from a Texas zoo, the viral DNA from the herpesvirus termed MCFV-WTD, which causes disease in white-tailed deer (Odocoileus virginianus), was detected. The epidemiology information revealed that the red brocket deer had been associated with a herd of pygmy goats (Capra hircus) at the zoo. MCFV-WTD DNA was also detected in one of these 12 goats that were malignant catarrhal fever viral antibody positive. The amplified herpesviral sequences from the affected deer and the MCFV-WTD-positive goat were identical, and matched the sequence in GenBank. Three of 123 DNA samples from various breeds of goats from different geographic locations in the United States were positive for MCFV-WTD DNA. The study shows that MCFV-WTD is capable of causing malignant catarrhal fever in other species of deer besides white-tailed deer and suggests that goats are a potential reservoir for the virus. PMID:23805572

Li, Hong; Cunha, Cristina W; Abbitt, Bruce; deMaar, Thomas W; Lenz, Stephen D; Hayes, Jeffrey R; Taus, Naomi S



Cystic mucinous tumors of the urachus: carcinoma in situ or adenoma of unknown malignant potential?  


Mucinous cystadenocarcinomas of the urachus are rare. Mucinous benign or premalignant tumors are even rarer, yet pose a challenge in diagnosis and management. We report a case of a 66-year-old man with lower abdominal pain who had a large cystic tumor at the dome of the bladder. En-bloc resection of the tumor with partial cystectomy revealed mucinous cystadenocarcinoma in situ. We reviewed the characteristics of all seven previously reported cases. These tumors are pre-malignant and can cause significant morbidity and mortality. They need to be treated similar to conventional mucinous cystadenocarcinoma by wide surgical resection and partial cystectomy. PMID:22704322

Fahed, Akl C; Nonaka, Daisuke; Kanofsky, Jamie A; Huang, William C



CD146 is a potential marker for the diagnosis of malignancy in cervical and endometrial cancer  

PubMed Central

Cluster of differentiation 146 (CD146) is an endothelial cell adhesion molecule which is overexpressed in various types of malignant cancer, including ovarian cancer. However, whether CD146 is overexpressed in another two types of gynecological cancer, cervical cancer and endometrial cancer, remains unclear. In the present study, we showed that CD146 expression levels were higher in cells from cervical cancer and endometrial cancer compared with their corresponding normal tissues, using anti-CD146 mouse antibody AA4 (mAb AA4) and that mAb AA4 exhibited a high performance for specificity, sensitivity and positive predictive value in the detection of these two types of cancer. CD146 expression was positively and significantly correlated with the pathological subtype of cervical cancer and with the histological grade and depth of myometrial invasion in endometrial cancer. In addition, we confirmed that CD146 is present in the majority of blood vessels in cervical and endometrial cancer, suggesting that CD146 may be actively implicated in the metastasis of cervical and endometrial cancer via the vascular system. Thus, this study provides insights for further development of CD146 mAb in the detection of gynecological malignant cancer types and implies that a combined treatment strategy of anti-CD146 immunotherapy with other traditional chemo- or radiotherapy treatments may be a promising approach against cervical and endometrial cancer.




Critical analysis of the potential for targeting STAT3 in human malignancy  

PubMed Central

The signal transducer and activator of transcription (STAT) family of proteins was originally discovered in the context of normal cell biology where they function to transduce intracellular and extracellular signals to the nucleus, ultimately leading to transcription of specific target genes and downstream phenotypic effects. It was quickly appreciated that the STATs, especially STAT3, play a fundamental role in human malignancy. In contrast to normal biology in which transient STAT3 signaling is strictly regulated by a tightly coordinated network of activators and deactivators, STAT3 is constitutively activated in human malignancies. Constitutive STAT3 signaling has been associated with many cancerous phenotypes across nearly all human cancers, including the upregulation of cell growth, proliferation, survival, and motility, among others. Studies involving candidate preclinical STAT3 inhibitors have further demonstrated that the reversal of these phenotypes results from pharmacologic or genetic inhibition of STAT3, suggesting that STAT3 may be a promising target for clinical interventions. Indeed, a Phase 0 clinical trial involving a STAT3 decoy oligonucleotide demonstrated that STAT3 is a drug-gable target in human tumors. Because of the ubiquity of overactive STAT3 in cancer, its role in promoting a wide variety of cancerous phenotypes, and the strong clinical and preclinical studies performed to date, STAT3 represents a promising target for the development of inhibitors for the treatment of human cancers.

Peyser, Noah D; Grandis, Jennifer R



Epigenetic Disregulation in Oral Cancer  

PubMed Central

Squamous cell carcinoma of the oral region (OSCC) is one of the most common and highly aggressive malignancies worldwide, despite the fact that significant results have been achieved during the last decades in its detection, prevention and treatment. Although many efforts have been made to define the molecular signatures that identify the clinical outcome of oral cancers, OSCC still lacks reliable prognostic molecular markers. Scientific evidence indicates that transition from normal epithelium to pre-malignancy, and finally to oral carcinoma, depends on the accumulation of genetic and epigenetic alterations in a multistep process. Unlike genetic alterations, epigenetic changes are heritable and potentially reversible. The most common examples of such changes are DNA methylation, histone modification, and small non-coding RNAs. Although several epigenetic changes have been currently linked to OSCC initiation and progression, they have been only partially characterized. Over the last decade, it has been demonstrated that especially aberrant DNA methylation plays a critical role in oral cancer. The major goal of the present paper is to review the recent literature about the epigenetic modifications contribution in early and later phases of OSCC malignant transformation; in particular we point out the current evidence of epigenetic marks as novel markers for early diagnosis and prognosis as well as potential therapeutic targets in oral cancer.

Mascolo, Massimo; Siano, Maria; Ilardi, Gennaro; Russo, Daniela; Merolla, Francesco; De Rosa, Gaetano; Staibano, Stefania



Increased IKK? Expression in the Basal Layer of the Epidermis of Transgenic Mice Enhances the Malignant Potential of Skin Tumors  

PubMed Central

Non-melanoma skin cancer is the most frequent type of cancer in humans. In this study we demonstrate that elevated IKK? expression in murine epidermis increases the malignancy potential of skin tumors. We describe the generation of transgenic mice overexpressing IKK? in the basal, proliferative layer of the epidermis and in the outer root sheath of hair follicles. The epidermis of K5-IKK? transgenic animals shows several alterations such as hyperproliferation, mislocalized expression of integrin-?6 and downregulation of the tumor suppressor maspin. Treatment of the back skin of mice with the mitogenic agent 12-O-tetradecanoylphorbol-13-acetate causes in transgenic mice the appearance of different preneoplastic changes such as epidermal atypia with loss of cell polarity and altered epidermal tissue architecture, while in wild type littermates this treatment only leads to the development of benign epidermal hyperplasia. Moreover, in skin carcinogenesis assays, transgenic mice carrying active Ha-ras (K5-IKK?-Tg.AC mice) develop invasive tumors, instead of the benign papillomas arising in wild type-Tg-AC mice also bearing an active Ha-ras. Therefore we provide evidence for a tumor promoter role of IKK? in skin cancer, similarly to what occurs in other neoplasias, including hepatocarcinomas and breast, prostate and colorectal cancer. The altered expression of cyclin D1, maspin and integrin-?6 in skin of transgenic mice provides, at least in part, the molecular bases for the increased malignant potential found in the K5-IKK? skin tumors.

Fernandez-Acenero, M. Jesus; Navarro, Manuel; Page, Angustias; Jorcano, Jose L.; Bravo, Ana; Ramirez, Angel; Casanova, M. Llanos



The CUL4A ubiquitin ligase is a potential therapeutic target in skin cancer and other malignancies.  


Cullin 4A (CUL4A) is an E3 ubiquitin ligase that directly affects DNA repair and cell cycle progression by targeting substrates including damage-specific DNA-binding protein 2 (DDB2), xeroderma pigmentosum complementation group C (XPC), chromatin licensing and DNA replication factor 1 (Cdt1), and p21. Recent work from our laboratory has shown that Cul4a-deficient mice have greatly reduced rates of ultraviolet-induced skin carcinomas. On a cellular level, Cul4a-deficient cells have great capacity for DNA repair and demonstrate a slow rate of proliferation due primarily to increased expression of DDB2 and p21, respectively. This suggests that CUL4A promotes tumorigenesis (as well as accumulation of skin damage and subsequent premature aging) by limiting DNA repair activity and expediting S phase entry. In addition, CUL4A has been found to be up-regulated via gene amplification or overexpression in breast cancers, hepatocellular carcinomas, squamous cell carcinomas, adrenocortical carcinomas, childhood medulloblastomas, and malignant pleural mesotheliomas. Because of its oncogenic activity in skin cancer and up-regulation in other malignancies, CUL4A has arisen as a potential candidate for targeted therapeutic approaches. In this review, we outline the established functions of CUL4A and discuss the E3 ligase's emergence as a potential driver of tumorigenesis. PMID:23845142

Hannah, Jeffrey; Zhou, Peng-Bo



Potential for cripto-1 in defining stem cell-like characteristics in human malignant melanoma.  


The diagnosis of melanoma is becoming ever more frequent. Although surgical excision of early lesions is associated with relatively significant high cure rates, treatment modalities are largely unsuccessful for advanced disease. Characteristics such as cellular heterogeneity and plasticity, expression of certain molecules such as the multidrug resistance protein-1 (MDR1) or the aberrant expression of embryonic signaling molecules and morphogens like Nodal, important for self renewal and pluripotency, suggest that a stem cell-like population may reside in aggressive melanomas. This perspective focuses on preliminary findings obtained in our laboratory which indicate that the expression of the Nodal coreceptor, Cripto-1, in a subset of malignant melanoma cells may be exploited to identify possible melanoma stem cells (MSC). In fact, the use of anti-Cripto-1 antibodies to cell sort Cripto-1-positive cells in the metastatic melanoma cell line C8161 has identified a slow growing, sphere forming subpopulation that expresses increased levels of Oct4, Nanog and MDR1. If current in vivo studies confirm the self renewal and tumorigenic characteristics of these cells, the expression of Cripto-1 may represent a useful marker to identify cancer stem cells in melanoma, and possibly other aggressive tumors as well. PMID:18604175

Strizzi, Luigi; Abbott, Daniel E; Salomon, David S; Hendrix, Mary J C



Plant and Fungal Food Components with Potential Activity on the Development of Microbial Oral Diseases  

PubMed Central

This paper reports the content in macronutrients, free sugars, polyphenols, and inorganic ions, known to exert any positive or negative action on microbial oral disease such as caries and gingivitis, of seven food/beverages (red chicory, mushroom, raspberry, green and black tea, cranberry juice, dark beer). Tea leaves resulted the richest material in all the detected ions, anyway tea beverages resulted the richest just in fluoride. The highest content in zinc was in chicory, raspberry and mushroom. Raspberry is the richest food in strontium and boron, beer in selenium, raspberry and mushroom in copper. Beer, cranberry juice and, especially green and black tea are very rich in polyphenols, confirming these beverages as important sources of such healthy substances. The fractionation, carried out on the basis of the molecular mass (MM), of the water soluble components occurring in raspberry, chicory, and mushroom extracts (which in microbiological assays revealed the highest potential action against oral pathogens), showed that both the high and low MM fractions are active, with the low MM fractions displaying the highest potential action for all the fractionated extracts. Our findings show that more compounds that can play a different active role occur in these foods.

Daglia, Maria; Papetti, Adele; Mascherpa, Dora; Grisoli, Pietro; Giusto, Giovanni; Lingstrom, Peter; Pratten, Jonathan; Signoretto, Caterina; Spratt, David A.; Wilson, Michael; Zaura, Egija; Gazzani, Gabriella



Oral gabapentin suppresses pentylenetetrazole-induced seizure-like behavior and cephalic field potential in adult zebrafish.  


We report the effect of orally administered gabapentin (GBP) on pentylenetetrazole (PTZ)-induced seizure-like activity in adult zebrafish. Zebrafish were pretreated with vehicle or GBP using a novel method of precise oral administration, followed by an intraperitoneal administration of PTZ. Behavioral assessment was carried out using locomotion-based video-tracking analysis and seizure score assignment using visual observation. Cephalic field potential recordings of the zebrafish brain were conducted using an electrical data acquisition system. Orally administered GBP significantly suppressed the seizure-like locomotor activity and strong slow-wave (~3Hz) activity in the cephalic field potential caused by PTZ. This work is the first report of the activity of an orally delivered anticonvulsant in adult zebrafish. Our study provides behavioral and physiological evidence in support of an adult zebrafish model for studying seizures including excitotoxic brain injury and a novel in vivo framework for the evaluation of pharmacological modulators of epilepsy. PMID:23466252

Banote, Rakesh Kumar; Koutarapu, Srinivas; Chennubhotla, Keerthana Sarma; Chatti, Kiranam; Kulkarni, Pushkar



The Oral History Rating Scale–Revised: Preliminary Evaluation of a Clinician-Rated Measure of Divorce Potential  

Microsoft Academic Search

This study was a preliminary psychometric investigation of the Oral History Rating Scale–Revised (OHRS–R), a therapist-rated measure of married couples' divorce potential based a 90-min oral history interview. Findings suggest the OHRS–R shows promise as a clinical tool. Therapist and observing raters' total OHRS–R scores demonstrated high interrater reliability and discriminated from client reports of psychological functioning (Outcome Questionnaire-45.2) and

Amber L. Brewer; D. Eugene Mead



Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats.  


Carbon tetrachloride (CCl4) is a model for studying free radical-induced liver injury and screening hepato-protective drugs. Numerous studies have reported the involvement of oxidative stress in CCl4-induced liver damage and the hepato-protective effects mediated by different antioxidants. The present study examined the effects of diphenyl diselenide, (PhSe)2, on hepatotoxicity induced by CCl4 in rats. To this end, male Wistar rats received (PhSe)2 by oral route at the dosage of 31.2 mg/kg for one or two days. After the second day of treatment, rats received CCl4 orally in a single dose. The liver and kidney were utilized for determination of histopathology, biochemical [aspartate (ALT) and alanine (AST) aminotransferases, alkaline phosphatase (ALP), total bilirrubin (TB) and gamaglutamyl transferase (GGT)] and toxicological parameters [thiobarbituric reactive species (TBARS) levels, catalase activity, ascorbic acid, nonprotein thiols (NPSH) and aminolevulinate dehydratase (-ALA-D) activity]. Repeated administration of (PhSe)2 caused a marked potentiation of hepatotoxicity induced by CCl4 exposure, as manifested by an increase in biochemical parameters (AST, ALT, ALP, GGT and BT) and severe alteration in histopathology. This study also demonstrated a potentiation of TBARS levels and a consequent depletion of important antioxidant defenses including catalase and ascorbic acid. Pre-treatment with a single dose of (PhSe)2 prevented the effect of strychnine, a substrate for CYPs, abolishing lethality in mice. This result indicates that (PhSe)2 prevented animal death, suggesting an activator action of (PhSe)2 in CYPs. This study clearly indicates that (PhSe)2 potentiated acute hepatic damage induced by CCl4. PMID:18989868

Nogueira, Cristina W; Borges, Lysandro Pinto; Souza, Ana Cristina Guerra



Chromoblastomycosis with malignant transformation and cutaneous-synovial secondary localization. The potential therapeutic role of itraconazole.  


A case of neoplastic transformation of lesions of chromoblastomycosis is reported in a 67-year-old farmer from French Guyana. An interesting aspect of this case was the appearance of new cutaneous lesions of chromoblastomycosis, in a different site from the original lesion, and the presence of an infected synovial cyst. The potential therapeutic role of itraconazole is discussed. PMID:1659631

Paul, C; Dupont, B; Pialoux, G; Avril, M F; Pradinaud, R



Insulin allergy in a diabetic patient: Potential factor to increase malignancy incidence  

Microsoft Academic Search

Diabetes mellitus is a universal disease, and insulin is essential to control patients' blood glucose level. In some clinical cases, the diabetic patients suffer from insulin allergy, and even some of them fall into allergic shock and death. In order to analyze the potential influence of insulin allergy on systematic organs, here we report a 64-year-old patient with type 2

Hui Zhao; Sheng Yu; Zhongshan Wang; Kaizhong Wang; Xiaoli Zhang; Yingli Lu



AYA Monograph Malignant Melanoma

Chapter 5 Malignant Melanoma ??????? ??????? ????????????? ?? ??????????????? ?? ??????????????? ??? ??????????? ???????? ?? ? ??????? ??? ?????? ??????? ??? ??????? ????????? ??? ??????????? ???????? ?? ?????????? ?? ??????????? ?????????????? ?? ????? ?? ????????????


Potential benefits and pitfalls of respiratory-gated radiotherapy in the treatment of thoracic malignancy.  


AIM: Despite advances in radiotherapy delivery, the prognosis of lung cancer remains poor. Higher doses of radiation have been associated with improved outcomes but may result in higher toxicities. Respiratory gated radiotherapy (RGRT) has the potential to reduce pulmonary toxicity but there are significant limitations and pitfalls to its use. The aim of this article is to (i) describe the RGRT technique currently employed at Nepean and Westmead Hospitals; (ii) discuss the practical issues of implementing such a program; (iii) present the results of our RGRT program and (iv) review the potential uncertainties in using this technique and the methods we have used to overcome these. METHODS: A retrospective review of all patients who had a 4D-computed tomography (4D-CT) scan was undertaken. Records from treatment planning systems were used to assess the prospective gating program. RESULTS: Between September 2007 and June 2011, 53 patients at Nepean and 26 patients at Westmead Hospital underwent a 4D-CT. Between April and August 2011, 26 patients at Westmead Hospital underwent a prospective 4D-CT scan as treatment verification. Two of the 26 patients (7.7%) were found to have incomplete coverage of the planning target volume. Both patients underwent respiratory re-coaching, alleviating the need for replanning. CONCLUSION: RGRT may reduce doses to organs at risk with the potential for dose escalation. However its implementation requires significant staff training, treatment time and resources. Treatment verification with image guided radiation therapy are essential for safe delivery. PMID:23298326

Hau, Eric; Rains, Melissa; Pham, Trang; Muirhead, Rebecca; Yeghiaian Alvandi, Roland



Oral calcitonin.  


Calcitonin is a hormone secreted by the C-cells of the thyroid gland in response to elevations of the plasma calcium level. It reduces bone resorption by inhibiting mature active osteoclasts and increases renal calcium excretion. It is used in the management of postmenopausal osteoporosis, Paget's disease of bone, and malignancy-associated hypercalcemia. Synthetic and recombinant calcitonin preparations are available; both have similar pharmacokinetic and pharmacodynamic profiles. As calcitonin is a peptide, the traditional method of administration has been parenteral or intranasal. This hinders its clinical use: adherence with therapy is notoriously low, and withdrawal from clinical trials has been problematic. An oral formulation would be more attractive, practical, and convenient to patients. In addition to its effect on active osteoclasts and renal tubules, calcitonin has an analgesic action, possibly mediated through ?-endorphins and the central modulation of pain perception. It also exerts a protective action on cartilage and may be useful in the management of osteoarthritis and possibly rheumatoid arthritis. Oral formulations of calcitonin have been developed using different techniques. The most studied involves drug-delivery carriers such as Eligen(®) 8-(N-2hydroxy-5-chloro-benzoyl)-amino-caprylic acid (5-CNAC) (Emisphere Technologies, Cedar Knolls, NJ). Several factors affect the bioavailability and efficacy of orally administered calcitonin, including amount of water used to take the tablet, time of day the tablet is taken, and proximity to intake of a meal. Preliminary results looked promising. Unfortunately, in two Phase III studies, oral calcitonin (0.8 mg with 200 mg 5-CNAC, once a day for postmenopausal osteoporosis and twice a day for osteoarthritis) failed to meet key end points, and in December 2011, Novartis Pharma AG announced that it would not pursue further clinical development of oral calcitonin for postmenopausal osteoporosis or osteoarthritis. A unique feature of calcitonin is that it is able to uncouple bone turnover, reducing bone resorption without affecting bone formation and therefore increasing bone mass and improving bone quality. This effect, however, may be dose-dependent, with higher doses inhibiting both resorption and formation. Because so many factors affect the pharmacokinetics and pharmacodynamics of calcitonin, especially orally administered calcitonin, much work remains to be done to explore the full pharmacologic spectrum and potential of calcitonin and determine the optimum dose and timing of administration, as well as water and food intake. PMID:23071417

Hamdy, Ronald C; Daley, Dane N



Malignant hyperthermia.  

PubMed Central

Malignant hyperthermia is a rare autosomal dominant trait that predisposes affected individuals to great danger when exposed to certain anaesthetic triggering agents (such as potent volatile anaesthetics and succinylcholine). A sudden hypermetabolic reaction in skeletal muscle leading to hyperthermia and massive rhabdomyolysis can occur. The ultimate treatment is dantrolene sodium a nonspecific muscle relaxant. Certain precautions should be taken before anaesthesia of patients known to be susceptible to malignant hyperthermia. These include the prohibition of the use of triggering agents, monitoring of central body temperature and expired CO2, and immediate availability of dantrolene. In addition, careful cleansing of the anaesthesia machine of vapours of halogenated agents is recommended. If these measures are taken, the chances of an MH episode are greatly reduced. When malignant hyperthermia-does occur in the operating room, prompt recognition and treatment usually prevent a potentially fatal outcome. The most reliable test to establish susceptibility to malignant hyperthermia is currently the in vitro caffeine-halothane contracture test. It is hoped that in the future a genetic test will be available.

Ben Abraham, R.; Adnet, P.; Glauber, V.; Perel, A.



Emergence of new oral antithrombotics: a critical appraisal of their clinical potential  

PubMed Central

In Western countries, venous thromboembolism (VTE) is a widespread and serious disorder, with hospital admission rates that appear to be increasing. Current anticoagulant therapies available for the prevention and treatment of VTE have several drawbacks that make them either difficult to manage effectively, due to a need for careful monitoring to control coagulation, or, in the case of parenterally administered agents, inconvenient for long-term use. To address some of these issues, new anticoagulants are in clinical development that can be orally administered and directly target specific factors in the coagulation cascade. This article reviews the rationale behind development of these novel agents and provides a critical appraisal of their clinical potential. In addition, the impact that the introduction of such agents into clinical practice would have is discussed from the patient perspective.

Lassen, Michael Rud; Laux, Volker



Genetic regulation and potentially therapeutic application of cancer-associated fibroblasts in oral cancer.  


Carcinoma-associated fibroblast (CAF) is the most important host cell type in tumor microenvironment, which greatly contributes to tumor initiation, progression, and metastasis. Therefore, a large amount of data has emerged, showing the cancer-promoting function of these cells via paracrine effects that escort tumor cells through all the steps of cancer development. CAF is a heterogeneous cell population that can arise from the differentiation of resting fibroblasts, epithelial cells, endothelial cells, and mesenchymal stem cells. This review summarizes the current knowledge of the role of CAFs in tumor progression, with a particular focus on the cellular and molecular features and recent advances in researches on the genetic status and microRNA regulation, and addresses the potential prognostic and therapeutic values for patients with oral cancer by targeting CAFs. PMID:23782231

Wang, Jingyi; Min, Anjie; Gao, Shan; Tang, Zhangui



Oral caffeine maintenance potentiates the reinforcing and stimulant subjective effects of intravenous nicotine in cigarette smokers  

Microsoft Academic Search

  Abstract\\u000a \\u000a \\u000a Rationale. Epidemiological, clinical and pre-clinical observations suggest that caffeine can potentiate the reinforcing and discriminative\\u000a effects of nicotine.\\u000a \\u000a \\u000a \\u000a \\u000a Objective. The present study examined whether chronic exposure to moderate doses of caffeine affects the reinforcing and subjective\\u000a effects of intravenously administered nicotine.\\u000a \\u000a \\u000a \\u000a \\u000a Methods. The effects of oral caffeine maintenance on the subjective and physiological effects of intravenously administered nicotine\\u000a and

Hendree E. Jones; Roland R. Griffiths



Oral Lichen Planus as a Preneoplastic Inflammatory Model  

PubMed Central

Oral lichen planus (OLP) is a chronic oral inflammatory disease of unknown etiology. According to reports, 1-2% of OLP patients develop oral squamous cell carcinoma (OSCC) in the long run. While World Health Organization (WHO) classifies OLP as “a potentially malignant disorder,” it is still a matter of debate which mechanisms drive OLP to such a condition. The current hypothesis connecting OLP and OSCC is that chronic inflammation results in crucial DNA damage which over time results in cancer development. Initial studies investigating the OLP and OSCC link were mainly retrospective clinical studies. Over the past years, several amount of information has accumulated, mainly from molecular studies on the OLP malignant potential. This article is a critical review of whether OLP has a malignant potential and, therefore, represents a model of preneoplastic inflammation.

Georgakopoulou, Eleni A.; Achtari, Marina D.; Achtaris, Michael; Foukas, Periklis G.; Kotsinas, Athanassios



The serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential antitumor target for psychotropics  

Microsoft Academic Search

Following our previous description of the serotonin transporter (SERT) acting as a conduit to 5- hydroxytryptamine (5-HT)-mediated apoptosis, specifically in Burkitt's lymphoma, we now detail its expression among a broad spectrum of B cell malignancy, while exploring additional SERT substrates for potential therapeutic activity. SERT was readily detected in derived B cell lines with origins as diverse as B cell

Elizabeth J. Meredith; Michelle J. Holder; Anita Chamba; Anita Challa; Adrian Drake Lee; Christopher M. Bunce; Mark T. Drayson; Geoffrey Pilkington; Randy D. Blakely; Martin J. S. Dyer; Nicholas M. Barnes; John Gordon



Immunohistochemical detection of p53 and p63 in oral squamous cell carcinoma, oral leukoplakia, and oral submucous fibrosis.  


AIM: Oral squamous cell carcinoma (OSCC) may be preceded by potentially malignant disorders such as leukoplakia and oral submucous fibrosis (OSF). p63 in concert with p53 regulates cell proliferation and differentiation and may have a role in potentially malignant and malignant lesions of the oral cavity. The aim of the study was to evaluate and compare the expression of p53 and p63 proteins in OSCC, leukoplakia, and OSF by immunohistochemistry (IHC). METHODS: Tissue sections of OSCC (n = 20), leukoplakia (n = 20), OSF (n = 20) and normal oral mucosa (n = 10) were stained with p53 and p63 antibodies by IHC. Mean labeling index (LI) among the study groups were compared using the Kruskal-Wallis test. RESULTS: The mean LI of p53 for OSCC, leukoplakia, OSF, and normal mucosa were 56.9 ± 21.3, 37.6 ± 12.6, 34.6 ± 8.7 and 15.1 ± 9, while mean LI of p63 were 56.8 ± 19.6, 42.3 ± 10.5, 32.8 ± 12.1, and 26.4 ± 9.4. The mean LI of p53 and p63 were significantly higher in OSCC, leukoplakia and OSF compared to normal mucosa (P < 0.01; P < 0.01). CONCLUSION: The significant increase in expression of p53 and p63 proteins in OSCC, leukoplakia, and OSF suggests their role as surrogate markers of malignant transformation. PMID:23776093

Varun, B R; Ranganathan, K; Rao, Umadevi K; Joshua, Elizabeth



Traditional Medicinal Plant Extracts and Natural Products with Activity Against Oral Bacteria: Potential Application in the Prevention and Treatment of Oral Diseases  

Microsoft Academic Search

Oral diseases are major health problems with dental caries and periodontal diseases among the most important preventable global infectious diseases. Oral health influences the general quality of life and poor oral health is linked to chronic conditions and systemic diseases. The associ- ation between oral diseases and the oral microbiota is well established. Of the more than 750 species of

Enzo A. Palombo



Potential impact of new oral anticoagulants on the management of atrial fibrillation-related stroke in primary care  

PubMed Central

Aim Anticoagulant prophylaxis with vitamin K antagonists (such as warfarin) is effective in reducing the risk of stroke in patients with atrial fibrillation (AF). New oral anticoagulants have emerged as potential alternatives to traditional oral agents. The purpose of this review was to summarise the effectiveness and safety of rivaroxaban, dabigatran and apixaban in stroke prevention in patients with AF in phase III trials, evaluate their cost-effectiveness and consider the implications for primary care. Methodology A literature search was performed between 2007 and 2012, selecting all phase III trials (ROCKET AF, RE-LY and ARISTOTLE) of new oral anticoagulants and relevant cost–benefit studies. Results Evidence shows that all three agents are at least as effective as warfarin in the prevention of stroke and systemic emboli, with similar safety profiles. Cost–benefit studies of rivaroxaban and dabigatran further confirm their potential use as alternatives to warfarin in clinical practice. These observations may allow stratification of the general practice AF population, to help prioritise which patients may benefit from receiving a new oral anticoagulant. Conclusion The clinical and economic benefits of the new oral anticoagulants, along with appropriate risk stratification, may enable a higher number of patients with AF to receive effective and convenient prophylaxis for stroke prevention.

Harris, K; Mant, J



Prevalence of potential respiratory pathogens in the mouths of elderly patients and effects of professional oral care  

Microsoft Academic Search

To evaluate the effectiveness of professional oral health care in reducing the risk of aspiration pneumonia, we examined the prevalence of potential respiratory pathogens in gargled samples from elderly persons. Samples were obtained from 54 elderly subjects over 65 years of age who required daily nursing care, from 21 healthy elderly subjects over 65 years old, and from 22 healthy

Shu Abe; Kazuyuki Ishihara; Katsuji Okuda




EPA Science Inventory

Three long-term studies were performed to evaluate the carcinogenic potential of the pesticide rotenone in hamsters and rats. Rotenone was administered orally to Wistar rats and by intraperitoneal injection to Sprague-Dawley rats, which were maintained and observed for 14 and 18 ...


Lysophosphatidic acid receptor 4 signaling potentially modulates malignant behavior in human head and neck squamous cell carcinoma cells  

PubMed Central

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common non-skin cancer worldwide. Despite improvement in therapeutic strategies, the prognosis of advanced HNSCC remains poor. The extacellular lipid mediators known as lysophosphatidic acids (LPAs) have been implicated in tumorigenesis of HNSCC. LPAs activate G-protein-coupled receptors not only in the endothelial differentiation gene (Edg) family (LPA1, LPA2, LPA3) but also in the phylogenetically distant non-Edg family (LPA4, LPA5, LPA6). The distinct roles of these receptor isoforms in HNSCC tumorigenesis have not been clarified. In the present study, we investigated the effect of ectopic expression of LPA4 in SQ-20B, an HNSCC cell line, expressing a trivial level of endogenous LPA4. LPA (18:1) stimulated proliferation of SQ-20B cells, but did not affect proliferation of HEp-2, an SCC cell line expressing higher levels of LPA4, comparable to those of with LPA1. LPA-stimulated proliferation of SQ-20B cells was attenuated by Ki16425 and Rac1 inhibitor, but not by Y-27632. Infection with doxycycline-regulatable adenovirus vector expressing green fluorescent protein-tagged LPA4 (AdvLPA4G) abolished LPA-stimulated proliferation in SQ-20B cells with the accumulation of G2/M-phasic cells. Ectopic LPA4 induction further downregulated proliferation of Ki16425-treated SQ-20B cells, of which downregulation was partially recovered by LPA. Ectopic LPA4 induction also downregulated proliferation of Rac1 inhibitor-treated SQ-20B cells, however, LPA no longer recovered it. Finally, LPA-induced cell motility was suppressed by ectopic LPA4 expression as well as by Ki16425, Rac1 inhibitor or Y-27632. Our data suggest that LPA4 signaling potentially modulates malignant behavior of SQ-20B cells. LPA signaling, which is mediated by both Edg and non-Edg receptors, may be a determinant of malignant behavior of HNSCC and could therefore be a promising therapeutic target.




A review of transcriptome studies combined with data mining reveals novel potential markers of malignant pleural mesothelioma.  


Malignant pleural mesothelioma (MPM), a cancer of the serosal pleural cavities, is one of the most aggressive human tumors. In order to identify genes crucial for the onset and progression of MPM, we performed an extensive literature review focused on transcriptome studies (RTS). In this kind of studies a great number of transcripts are analyzed without formulating any a priori hypothesis, thus preventing any bias coming from previously established knowledge that could lead to an over-representation of specific genes. Each study was thoroughly analyzed paying particular attention to: (i) the employed microarray platform, (ii) the number and type of samples, (iii) the fold-change, and (iv) the statistical significance of deregulated genes. We also performed data mining (DM) on MPM using three different tools (Coremine, SNPs3D, and GeneProspector). Results from RTS and DM were compared in order to restrict the number of genes potentially deregulated in MPM. Our main requirement for a gene to be a "mesothelioma gene" (MG) is to be reproducibly deregulated among independent studies and confirmed by DM. A list of MGs was thus produced, including PTGS2, BIRC5, ASS1, JUNB, MCM2, AURKA, FGF2, MKI67, CAV1, SFRP1, CCNB1, CDK4, and MSLN that might represent potential novel biomarkers or therapeutic targets for MPM. Moreover, it was found a sub-group of MGs including ASS1, JUNB, PTGS2, EEF2, SULF1, TOP2A, AURKA, BIRC5, CAV1, IFITM1, PCNA, and PKM2 that could explain, at least in part, the mechanisms of resistance to cisplatin, one first-line chemotherapeutic drug used for the disease. Finally, the pathway analysis showed that co-regulation networks related to the cross-talk between MPM and its micro-environment, in particular involving the adhesion molecules, integrins, and cytokines, might have an important role in MPM. Future studies are warranted to better characterize the role played by these genes in MPM. PMID:22198210

Melaiu, Ombretta; Cristaudo, Alfonso; Melissari, Erika; Di Russo, Manuela; Bonotti, Alessandra; Bruno, Rossella; Foddis, Rudy; Gemignani, Federica; Pellegrini, Silvia; Landi, Stefano



Nanoparticles as potential oral delivery systems of proteins and vaccines: A mechanistic approach  

Microsoft Academic Search

Peptides and proteins remain poorly bioavailable upon oral administration. One of the most promising strategies to improve their oral delivery relies on their association with colloidal carriers, e.g. polymeric nanoparticles, stable in gastrointestinal tract, protective for encapsulated substances and able to modulate physicochemical characteristics, drug release and biological behavior. The mechanisms of transport of these nanoparticles across intestinal mucosa are

Anne des Rieux; Virginie Fievez; Marie Garinot; Yves-Jacques Schneider; Véronique Préat



Peroxiredoxin I expression in oral cancer: a potential new tumor marker  

Microsoft Academic Search

This study investigates the applicability of the novel antioxidant protein, peroxiredoxin (Prx) I as a marker for tumor status in oral squamous cell carcinoma (SCC). Samples from 53 patients with SCC in the oral cavity were examined by immunohistochemistry. Correlations between the expression level of Prx I and proliferating cell nuclear antigen (PCNA), the clinical features of tumors, and their

Toru Yanagawa; Satoshi Iwasa; Tetsuro Ishii; Katsuhiko Tabuchi; Hiroshi Yusa; Kojiro Onizawa; Ken Omura; Hiroyuki Harada; Haruhiko Suzuki; Hiroshi Yoshida



Varespladib methyl, an oral phospholipase A2 inhibitor for the potential treatment of coronary artery disease.  


Varespladib methyl is an oral secretory phospholipase A2 inhibitor that is being developed by Anthera Pharmaceuticals Inc for the potential treatment of coronary artery disease, acute coronary syndrome and inflammation. Varespladib methyl is a prodrug that is rapidly metabolized to varespladib, and both compounds are able to potently inhibit the enzymes of the human secretory phospholipase groups IIa, V and X, which play a pivotal role in atherosclerotic disease and inflammation. Phase II clinical trials of varespladib methyl in patients with coronary artery disease, rheumatoid arthritis, asthma and ulcerative colitis revealed that the drug was well tolerated. Varespladib methyl did not demonstrate a good efficacy profile in patients with rheumatoid arthritis, asthma and ulcerative colitis, whereas in patients with coronary artery disease, varespladib methyl consistently reduced LDL-cholesterol levels (elevated LDL-cholesterol levels are a marker of increased cardiovascular risk). At the time of publication, phase II trials were ongoing in patients with acute coronary syndrome and in patients undergoing elective percutaneous coronary intervention, and a phase III trial in patients with acute coronary syndrome was planned. Varespladib methyl could represent a novel therapy for the treatment of cardiovascular disease, although the efficacy, safety profile and advantages of this drug compared with existing therapeutic options would need to be established in upcoming phase III trials. PMID:19697278

Karakas, Mahir; Koenig, Wolfgang



Identification of Tetranectin as a Potential Biomarker for Metastatic Oral Cancer  

PubMed Central

Lymph node involvement is the most important predictor of survival rates in patients with oral squamous cell carcinoma (OSCC). A biomarker that can indicate lymph node metastasis would be valuable to classify patients with OSCC for optimal treatment. In this study, we have performed a serum proteomic analysis of OSCC using 2-D gel electrophoresis and liquid chromatography/tandem mass spectrometry. One of the down-regulated proteins in OSCC was identified as tetranectin, which is a protein encoded by the CLEC3B gene (C-type lectin domain family 3, member B). We further tested the protein level in serum and saliva from patients with lymph-node metastatic and primary OSCC. Tetranectin was found significantly under-expressed in both serum and saliva of metastatic OSCC compared to primary OSCC. Our results suggest that serum or saliva tetranectin may serve as a potential biomarker for metastatic OSCC. Other candidate serum biomarkers for OSCC included superoxide dismutase, ficolin 2, CD-5 antigen-like protein, RalA binding protein 1, plasma retinol-binding protein and transthyretin. Their clinical utility for OSCC detection remains to be further tested in cancer patients.

Arellano-Garcia, Martha E.; Li, Roger; Liu, Xiaojun; Xie, Yongming; Yan, Xiaofei; Loo, Joseph A.; Hu, Shen



Comparative evaluation of two structurally related flavonoids, isoliquiritigenin and liquiritigenin, for their oral infection therapeutic potential.  


Isoliquiritigenin (1) and liquiritigenin (2) are structurally related flavonoids found in a variety of plants. The purpose of this study was to perform a comparative analysis of biological properties of these compounds in regard to their therapeutic potential for oral infections. Compound 1 demonstrated significant antibacterial activity against three major periodontopathogens, Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia. In contrast, 2 exerted less pronounced effects on the above bacterial species. Neither compound was effective against cariogenic bacteria (Streptococcus mutans and Streptococcus sobrinus). Furthermore, 1 exhibited a stronger inhibitory activity than 2 toward P. gingivalis collagenase and human matrix metalloproteinase 9. Finally, the capacity of 1 to attenuate the inflammatory response of macrophages induced by Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS) was much higher when compared to 2. The activation of transcriptional factors nuclear factor-?B (NF-?B) p65 and activator protein-1 (AP-1) associated with the LPS-induced inflammatory response in macrophages was inhibited strongly by 1, but less affected by 2. PMID:21866899

Feldman, Mark; Santos, Juliana; Grenier, Daniel



The oral microbiome in health and disease and the potential impact on personalized dental medicine.  


Every human body contains a personalized microbiome that is essential to maintaining health but capable of eliciting disease. The oral microbiome is particularly imperative to health because it can cause both oral and systemic disease. The oral microbiome rests within biofilms throughout the oral cavity, forming an ecosystem that maintains health when in equilibrium. However, certain ecological shifts in the microbiome allow pathogens to manifest and cause disease. Severe forms of oral disease may result in systemic disease at different body sites. Microbiomics and metagenomics are two fields of research that have emerged to identify the presence of specific microbes in the body and understand the nature of the microbiome activity during both health and disease. The analysis of the microbiome and its genomes will pave the way for more effective therapeutic and diagnostic techniques and, ultimately, contribute to the development of personalized medicine and personalized dental medicine. PMID:21902769

Zarco, M F; Vess, T J; Ginsburg, G S



Oral Myiasis is a Potential Risk in Patients with Special Health Care Needs.  


Myiasis is a rare disease caused by invasion of tissue by larvae of certain dipteran flies. It is more common in countries with tropical climate. Oral myiasis is not a very common condition and many clinicians are unaware of its diagnosis. Common predisposing factors are poor oral hygiene, halitosis, trauma, senility, learning disabilities, physically and mentally challenged conditions. Oral myiasis can lead to rapid tissue destruction and disfigurement and requires immediate treatment. Treatment consists of manual removal of maggots from oral cavity after application of chemical agents. Use of antibiotics reduces the duration of infection and hastens the recovery period. Good sanitation, personal and environmental hygiene and cleanliness and special care for debilitated persons are the best methods to prevent oral myiasis. PMID:22529629

Sharma, Akhilesh



Oral Myiasis is a Potential Risk in Patients with Special Health Care Needs  

PubMed Central

Myiasis is a rare disease caused by invasion of tissue by larvae of certain dipteran flies. It is more common in countries with tropical climate. Oral myiasis is not a very common condition and many clinicians are unaware of its diagnosis. Common predisposing factors are poor oral hygiene, halitosis, trauma, senility, learning disabilities, physically and mentally challenged conditions. Oral myiasis can lead to rapid tissue destruction and disfigurement and requires immediate treatment. Treatment consists of manual removal of maggots from oral cavity after application of chemical agents. Use of antibiotics reduces the duration of infection and hastens the recovery period. Good sanitation, personal and environmental hygiene and cleanliness and special care for debilitated persons are the best methods to prevent oral myiasis.

Sharma, Akhilesh



Early loss of mitochondrial inner transmembrane potential in khat-induced cell death of primary normal human oral cells.  


Previous studies suggest the use of khat, a psychostimulant plant used by millions of people in Middle East and Africa, as risk factor for oral cancer. We previously reported that khat is able to induce adverse affects, as cell cycle arrest and apoptosis, in normal human oral cells cultured in vitro. This study further investigates the more specific role played by mitochondria in khat-induced cell death and the kinetics of the events involved in this process. Exposure of primary normal human oral keratinocytes and fibroblasts to khat extract resulted in a swift and sustained decrease of the mitochondrial inner transmembrane potential occurring within 0.5-1h. Loss of mitochondrial membrane potential preceded all other biochemical and morphologic changes, and was associated with a significant decrease in cell survival. Subsequently, apoptosis-inducing factor was released from mitochondria into cytosol and relocated to nucleus. Cyclosporine A and bongkrekic acid delayed both the loss of mitochondrial inner transmembrane potential and the onset of cell death. This study describes a novel mechanism of khat-induced cell death in primary normal oral keratinocytes and fibroblasts involving an early pivotal effect on mitochondrial function and integrity. PMID:19591894

Lukandu, Ochiba M; Bredholt, Therese; Neppelberg, Evelyn; Gjertsen, Bjørn T; Johannessen, Anne C; Vintermyr, Olav K; Costea, Daniela Elena



Pseudoprogression in patients with malignant gliomas treated with concurrent temozolomide and radiotherapy: potential role of p53.  


We investigated pseudoprogression (psPD) in patients with malignant gliomas treated with radiotherapy (RT) and maintenance temozolomide (TMZ) in terms of incidence, outcomes, and predictive and prognostic factors. We evaluated p53 overexpression by immunohistochemical analysis of thirty-five tumor samples as a predictor for psPD. The time to progression and overall survival were compared between subgroups, psPD versus early progression (ePD) versus nonprogression (nonPD). Eight patients developed psPD among eighteen patients with lesion enlargement at the first MRI scan, and the others were classified as ePD. The remaining stable or improved patients were classified as nonPD. All patients with psPD were alive at last follow-up (median follow-up period was 12 months; range 5.8-58.5 months). Overall survival of psPD patients was significantly higher than ePD patients (P < 0.01). There was no significant survival difference between the psPD group and nonPD group (P = 0.25). Seven (87.5%) of eight tumors with psPD showed p53 overexpression, as compared to 3 (30%) of the ten tumors with ePD (P = 0.03). Our study indicates that psPD following chemoradiotherapy with TMZ is associated with significantly better overall survival compared to that of ePD, and is comparable to nonPD group. Overexpression of p53 was identified as a potential biomarker for predicting the development of psPD. PMID:20632071

Kang, Hyun-Cheol; Kim, Chae-Yong; Han, Jung Ho; Choe, Ghee Young; Kim, Jae Hyoung; Kim, Jee Hyun; Kim, In Ah



Dual targeting of AKT and mammalian target of rapamycin: a potential therapeutic approach for malignant peripheral nerve sheath tumor.  


The mammalian target of rapamycin (mTOR) pathway may constitute a potential target for the treatment of malignant peripheral nerve sheath tumors (MPNST). However, investigations of other cancers suggest that mTOR blockade can paradoxically induce activation of prosurvival, protumorigenic signaling molecules, especially upstream AKT. Consequently, we hypothesized that dual phosphatidylinositol 3-kinase (PI3K)/AKT-mTOR blockade might be applicable for MPNST treatment. Expression of activated mTOR downstream targets (p4EBP1 and pS6RP) and pAKT was evaluated immunohistochemically in a tissue microarray of human MPNSTs (n = 96) and benign neurofibromas (n = 31). Results were analyzed by Wilcoxon rank-sum tests. mTOR and AKT pathways in human MPNST cell lines, and the effects of rapamycin (mTOR inhibitor), LY294002 (dual PI3K/mTOR inhibitor), and PI-103 (potent dual PI3K/AKT-mTOR inhibitor) on pathway activation were evaluated by Western blot. Effects on cell growth were evaluated via MTS and colony formation assays. Cell cycle progression and apoptosis were assessed by propidium iodide/fluorescence-activated cell sorting staining and Annexin V assays. Acridine orange staining/fluorescence-activated cell sorting analysis, electron microscopy, and Western blot evaluated autophagy induction. p4EBP1, pS6Rp, and pAKT levels were found to be significantly higher in MPNST versus neurofibroma (P < 0.05 for all markers). mTOR and AKT pathways were found to be highly activated in MPNST cell lines. MPNST cells were sensitive to rapamycin; however, rapamycin enhanced pAKT and peIF4E expression. PI-103 abrogated MPNST cell growth and induced G(1) cell cycle arrest potentially through repression of cyclin D1. PI-103 did not elicit apoptosis but significantly induced autophagy in MPNST cells. These results suggest further study of combined PI3K/AKT and mTOR inhibition as a novel therapy for patients harboring MPNST. PMID:19417153

Zou, Changye Y; Smith, Kerrington D; Zhu, Quan-Sheng; Liu, Jun; McCutcheon, Ian E; Slopis, John M; Meric-Bernstam, Funda; Peng, Zhenghong; Bornmann, William G; Mills, Gordon B; Lazar, Alexander J; Pollock, Raphael E; Lev, Dina



762. Cisplatin-Induced DNA Damage Repair Mechanism Potentiates the Synergistic Efficacy of Oncolytic Herpes Simplex Viral Therapy in the Treatment of Malignant Mesothelioma  

Microsoft Academic Search

Background: NV1066, a replication-competent oncolytic herpes simplex virus attenuated by deletion of the viral replicative gene ?134.5, preferentially replicates in and kills malignant cells. ?134.5 codes for the protein ICP 34.5, which is homologous to the cisplatin-induced stress response protein GADD34 (Growth Arrest and DNA Damage 34). We hypothesize that cisplatin-induced GADD34 upregulation enhances viral replication and potentiates NV1066 efficacy.Methods:

Prasad S. Adusumilli; Mei-Ki Chan; David P. Eisenberg; Zhenkun Yu; Karen Hendershott; Ting-Chao Chou; Valerie W. Rusch; Yuman Fong



Salivary changes and dental caries as potential oral markers of autoimmune salivary gland dysfunction in primary Sj?gren's syndrome  

PubMed Central

Background the classification criteria for primary Sjögren's syndrome (pSS) include a number of oral components. In this study we evaluated if salivary flow and composition as well as dental caries are oral markers of disease severity in pSS. Methods in 20 patients fulfilling the American-European Consensus criteria for pSS and 20 age-matched healthy controls whole and parotid saliva flow rates and composition, measures of oral dryness, scores of decayed, missing and filled tooth surfaces (DMFS), periodontal indices, oral hygiene, and dietary habits were examined. Results in pSS, salivary flow rates, pH, and buffer capacities were lower, and DMFS, salivary sodium and chloride concentrations higher than in the healthy controls. DMFS also correlated inversely to salivary flow rates and positively to oral dryness. Apart from slightly increased gingival index, and more frequent dental visits in pSS, the periodontal condition, oral hygiene or sugar intake did not differ between these two groups. In pSS, findings were correlated to labial salivary gland focus score (FS) and presence of serum-autoantibodies to SSA/SSB (AB). The patients having both presence of AB and the highest FS (>2) also had the highest salivary sodium and chloride concentrations, the lowest salivary phosphate concentrations, lowest salivary flow rates, and highest DMFS compared to those with normal salivary concentrations of sodium and chloride at a given flow rate. Conclusion the salivary changes observed in some pSS patients reflect impaired ductal salt reabsorption, but unaffected acinar transport mechanisms, despite low salivary secretion. Our results suggest that changes in salivary flow and composition as well as dental caries may serve as potential markers of the extent of autoimmune-mediated salivary gland dysfunction in pSS. The study also indicates that the ductal epithelium is functionally affected in some pSS patients, which calls for future pathophysiological studies on the mechanisms underlying this impaired salt reabsorption.

Pedersen, Anne Marie Lynge; Bardow, Allan; Nauntofte, Birgitte



Evaluation of oncofetal protein-related mRNA transport activity as a potential early cancer marker in dogs with malignant neoplasms.  


A 55-kd protein with mRNA transport activity found in fetal rat liver cells and plasma from mice, rats, and human beings with malignant neoplasms has been designated oncofetal protein 55 (OFP55). Monoclonal antibody produced to rat OFP55 cross-reacts with human OFP55. Using this monoclonal antibody in a bioassay measuring mRNA transport stimulated by OFP55, we tested the plasma from 19 dogs with a variety of malignant neoplasms, including carcinomas, sarcomas, lymphomas, and melanomas, and compared the results with plasma from 20 clinically normal dogs without evidence of neoplasia. The mean mRNA transport activity from the group of dogs with malignant neoplasms was 0.43 +/- 0.28%/mg of protein. Mean transport activity from the group of control dogs was 0.04 +/- 0.02%/mg of protein. These means were significantly different (P < 0.0001). The degree of overlap between these 2 groups in their OFP55-related mRNA transport activity was minimal, and measurement of this protein appears to have potential for the early detection of malignant neoplasms in dogs. PMID:8599514

Stromberg, P C; Schumm, D E; Webb, T E; Ward, H; Couto, C G



Potential Role for a Carbohydrate Moiety in Anti-Candida Activity of Human Oral Epithelial Cells  

PubMed Central

Candida albicans is both a commensal and a pathogen at the oral mucosa. Although an intricate network of host defense mechanisms are expected for protection against oropharyngeal candidiasis, anti-Candida host defense mechanisms at the oral mucosa are poorly understood. Our laboratory recently showed that primary epithelial cells from human oral mucosa, as well as an oral epithelial cell line, inhibit the growth of blastoconidia and/or hyphal phases of several Candida species in vitro with a requirement for cell contact and with no demonstrable role for soluble factors. In the present study, we show that oral epithelial cell-mediated anti-Candida activity is resistant to gamma-irradiation and is not mediated by phagocytosis, nitric oxide, hydrogen peroxide, and superoxide oxidative inhibitory pathways or by nonoxidative components such as soluble defensin and calprotectin peptides. In contrast, epithelial cell-mediated anti-Candida activity was sensitive to heat, paraformaldehyde fixation, and detergents, but these treatments were accompanied by a significant loss in epithelial cell viability. Treatments that removed existing membrane protein or lipid moieties in the presence or absence of protein synthesis inhibitors had no effect on epithelial cell inhibitory activity. In contrast, the epithelial cell-mediated anti-Candida activity was abrogated after treatment of the epithelial cells with periodic acid, suggesting a role for carbohydrates. Adherence of C. albicans to oral epithelial cells was unaffected, indicating that the carbohydrate moiety is exclusively associated with the growth inhibition activity. Subsequent studies that evaluated specific membrane carbohydrate moieties, however, showed no role for sulfated polysaccharides, sialic acid residues, or glucose- and mannose-containing carbohydrates. These results suggest that oral epithelial cell-mediated anti-Candida activity occurs exclusively with viable epithelial cells through contact with C. albicans by an as-yet-undefined carbohydrate moiety.

Steele, Chad; Leigh, Janet; Swoboda, Rolf; Ozenci, Hatice; Fidel, Paul L.



Stromal myofibroblasts in oral leukoplakia and oral squamous cell carcinoma  

PubMed Central

Objectives: Oral leukoplakia (OL) is the main potentially malignant disorder and oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral mucosa. Stromal myofibroblasts play an important role in tumor invasion and metastasis, due to its ability to modify the extracellular matrix. This study aimed to evaluate the presence of stromal myofibroblasts in OL and OSCC. Differences in the presence of myofibroblasts among OL with distinct grades of epithelial dysplasia as well as between histologically high- and low-invasive OSCC were also assessed. Study Design: A total of 30 OL and 41 OSCC from archival formalin-fixed, paraffin-embedded specimens were evaluated. 10 samples of normal oral mucosa were used as a control. Myofibroblasts were identified by immunohistochemical detection of alpha smooth muscle actin and its presence was classified as negative, scanty or abundant. Differences in the presence of myofibroblasts among OL with distinct grades of epithelial dysplasia as well as between high- and low-invasive OSCC were analyzed using the Mann-Whitney test. Results: Myofibroblasts were not detected in normal oral mucosa and OL, whatever its histological grade. In OSCC, the presence of stromal myofibroblasts was classified as negative in 11 (26.8%), scanty in 15 (36.6%), and abundant in 15 samples (36.6%). The presence of stromal myofibroblasts was statistically higher in high-invasive OSCC than in low-invasive OSCC (p<0.05). Conclusions: Stromal myofibroblasts were not detected in OL, indicating that these cells are not important during oral carcinogenesis. Nevertheless, stromal myofibroblasts were heterogeneously detected in OSCC and its presence was higher in tumors with a more diffuse histological pattern of invasion. These findings suggest that myofibroblasts are associated with the creation of a permissive environment for tumor invasion in OSCC. Key words:Leukoplakia, oral squamous cell carcinoma, myofibroblast.

de-Assis, Eliene M.; Pimenta, Luiz G.G.S.; Costa-e-Silva, Edson; Souza, Paulo E.A.



Oral tolerance in neonates: from basics to potential prevention of allergic disease.  


Oral tolerance refers to the observation that prior feeding of an antigen induces local and systemic immune tolerance to that antigen. Physiologically, this process is probably of central importance for preventing inflammatory responses to the numerous dietary and microbial antigens present in the gut. Defective oral tolerance can lead to gut inflammatory disease, food allergies, and celiac disease. In the last two cases, the diseases develop early in life, stressing the necessity of understanding how oral tolerance is set up in neonates. This article reviews the parameters that have been outlined in adult animal models as necessary for tolerance induction and assesses whether these factors operate in neonates. In addition, we highlight the factors that are specific for this period of life and discuss how they could have an impact on oral tolerance. We pay particular attention to maternal influence on early oral tolerance induction through breast-feeding and outline the major parameters that could be modified to optimize tolerance induction in early life and possibly prevent allergic diseases. PMID:20485330

Verhasselt, V



Chromosome 3 Anomalies Investigated by Genome Wide SNP Analysis of Benign, Low Malignant Potential and Low Grade Ovarian Serous Tumours  

PubMed Central

Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains unknown. Histological and genetic evidence has led to the proposal that low grade ovarian serous carcinomas (LGOSC) have a different etiology than high grade carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP). Common regions of chromosome (chr) 3 loss have been observed in all types of serous ovarian tumours, including benign, suggesting that these regions contain genes important in the development of all ovarian serous carcinomas. A high-density genome-wide genotyping bead array technology, which assayed >600,000 markers, was applied to a panel of serous benign and LMP tumours and a small set of LGOSC, to characterize somatic events associated with the most indolent forms of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and BRAF mutations. An increasing frequency of genomic anomalies was observed with pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and 10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all tumour types. Runs of homozygosity were most commonly observed on chr3, with the 3p12-p11 candidate tumour suppressor region the most frequently homozygous region in the genome. An LMP harboured a homozygous deletion on chr6 which created a GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types. Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS-mutation positive LMP cases displayed significantly more chromosomal aberrations than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of 12p, which harbours the KRAS gene, was particularly evident. A pathology review reclassified all TP53-mutation positive LGOSC cases, some of which acquired a HGOSC status. Taken together, our results support the view that LGOSC could arise from serous benign and LMP tumours, but does not exclude the possibility that HGOSC may derive from LMP tumours.

Birch, Ashley H.; Arcand, Suzanna L.; Oros, Kathleen K.; Rahimi, Kurosh; Watters, A. Kevin; Provencher, Diane; Greenwood, Celia M.; Mes-Masson, Anne-Marie; Tonin, Patricia N.



TdT expression in Merkel cell carcinoma: potential diagnostic pitfall with blastic hematological malignancies and expanded immunohistochemical analysis  

Microsoft Academic Search

Merkel cell carcinoma is an uncommon aggressive primary cutaneous neuroendocrine carcinoma. Histologically, the differential diagnosis includes the ‘small round cell’ tumor group, particularly metastatic small cell carcinoma and blastic hematological malignancies involving skin\\/soft tissues. Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase, which is a sensitive and specific antibody for acute lymphoblastic lymphoma with a small proportion of acute myeloid

Monalisa Sur; Hosam AlArdati; Cathy Ross; Salem Alowami



Phytochemical determination and extraction of Momordica charantia fruit and its hypoglycemic potentiation of oral hypoglycemic drugs in diabetes mellitus (NIDDM).  


Momordica charantia (MC) fruit was subjected to phytochemical and pharmacological interaction studies with oral hypoglycemis in NIDDM patients. Phytochemical, chromatographical analysis and extraction of methanolic MC fruit soft (semi-solid form) in CCl4 + C6H6 solvent system yielded 15 diverse chemical constituents--alkaloids, glycosides, aglycone, tannin, sterol, phenol and protein. The CCl4 + C6H6 MC soft extract was used orally in a dose of 200 mg twice daily (BD) for pharmacological interactions with two diversely acting oral hypoglycemic agents--1) metformin BD and 2) glibenclamide BD in 15 patients of either sex (52-65 years of age) of NIDDM. It was observed that with CCl4 + C6H6 MC soft extract plus half doses of metformin or glibenclamide or both in combination caused hypoglycemia greater than that caused by full doses used in the study with 7 days treatment. Conclusively the extract acts in synergism with oral hypoglycemics and potentiates their hypoglycemia in NIDDM. PMID:15521566

Tongia, Abhishek; Tongia, Sudhir Kumar; Dave, Mangala



Assessment of the allergic potential of food protein extracts and proteins on oral application using the brown Norway rat model.  

PubMed Central

The need for widely accepted and validated animal models to test the potential allergenicity and potency of novel (biotechnology-derived) proteins has become an important issue for their safety evaluation. In this article, we summarize the results of the development of an oral sensitization protocol for food proteins in the rat. Young Brown Norway rats were exposed to either various purified allergenic proteins (e.g., ovalbumin, partly purified), a whole food (cow's milk), or total protein extracts (hen's egg white, peanut) by daily gavage dosing during 42 days without the use of an adjuvant. The results showed that Brown Norway rats can be sensitized orally to the various allergenic food proteins tested, resulting in antigen-specific immunoglobulin (Ig) G and IgE responses, without the use of adjuvants. Animals orally exposed to cow's milk or total protein extracts of egg white also developed specific IgE and IgG antibodies that recognized the same proteins compared with antibodies from patients allergic to egg white or cow's milk. We also studied local and systemic immune-mediated effects. In ovalbumin-sensitized rats, some clinical symptoms of food allergy were studied upon an oral challenge with ovalbumin. The results demonstrated that gut permeability was increased and that in some animals breathing frequency and systolic blood pressure were temporarily decreased. The results obtained show that the Brown Norway rat provides a suitable animal model for food allergy research and for the study of relative allergenicity of existing and novel food proteins.

Knippels, Leon M J; Penninks, Andre H



Crystalline nanosuspensions as potential toxicology and clinical oral formulations for BCS II/IV compounds.  


Nanosuspensions, formulations based on the reduction of the active pharmaceutical ingredient (API) particle size in the sub-micron range and most typically around 100-200 nm, represent a valuable option for formulators to facilitate oral absorption of Biopharmaceutics Classification System class II and IV compounds. Their ability to increase the API dissolution rate and subsequent absorption and thus oral bioavailability has been demonstrated in preclinical and clinical settings. This review summarizes the current experience in the biopharmaceutic field with the use of nanosuspensions as oral delivery formulations. The principles behind nanosuspensions as well as the in vitro and in silico evaluation are discussed, while examples are presented highlighting both successes as well as limitations in their application as either toxicology or clinical formulations. PMID:22736294

Kesisoglou, Filippos; Mitra, Amitava



Second malignancies after prostate brachytherapy: Incidence of bladder and colorectal cancers in patients with 15 years of potential follow-up  

SciTech Connect

Purpose: To report the incidence of second bladder and colorectal cancers after prostate brachytherapy. Methods and Materials: This review included 125 patients treated with I-125 brachytherapy alone, and 223 patients who received supplemental external beam radiation therapy. Median follow-up was 10.5 years. Patients were followed for the development of lower genitourinary and colorectal cancers. Second malignancies arising five years after radiation therapy were defined as being potentially associated with treatment; observed rates were then compared with age-matched expected rates according to Surveillance, Epidemiology, and End Results data. Results: Five years out of treatment, there were 15 patients with a second solid tumor, including bladder cancer (n = 11), colorectal cancer (n = 3), and prostatic urethra cancer (n = 1). The incidence of second malignancy was no different in patients treated with brachytherapy alone (1.6%) vs. those receiving external beam radiotherapy (5.8%, p = 0.0623). There were more observed bladder cancers compared with those expected (relative risk, 2.34, 95% confidence interval 0.96-3.72; absolute excess risk 35 cancers per 10,000 patients). Relative risk did not significantly change over increasing follow-up intervals up to 20 years after treatment. Conclusions: There may be an increased but small risk of developing a second malignancy after radiation therapy for prostate cancer. This outcome could be related to radiation carcinogenesis, but more vigilant screening and thorough workup as a result of radiation side effects and predisposing conditions (e.g., genetic and environmental factors) in many of the patients found to have second malignancies likely contributed to the higher number of observed malignancies than expected.

Liauw, Stanley L. [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, IL (United States); Sylvester, John E. [Seattle Prostate Institute at Swedish Hospital, Seattle, WA (United States) and Swedish Cancer Center at Stevens Hospital, Edmonds, WA (United States)]. E-mail:; Morris, Christopher G. [Department of Radiation Oncology, University of Florida, College of Medicine, Gainesville, FL (United States); Blasko, John C. [Seattle Prostate Institute at Swedish Hospital, Seattle, WA (United States); Grimm, Peter D. [Seattle Prostate Institute at Swedish Hospital, Seattle, WA (United States)



Cytologic diagnosis of low-grade papillary urothelial neoplasms (low malignant potential and low-grade carcinoma) in the context of the 1998 WHO/ISUP classification.  


The 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification of urothelial neoplasms introduced a category called papillary neoplasm of low malignant potential (LMP) and separated it from low-grade papillary urothelial carcinoma (LGPUC), which was thought to yield abnormal cells in cytology specimens. The objective of our study was to evaluate the effectiveness of urine cytology in diagnosing these lesions. Eighty-six paired transurethral surgical biopsy and corresponding urine cytology specimens representing the spectrum of urothelial papillary lesions were examined. Consensus diagnosis on each biopsy was made, and the distribution was as follows: 16 benign urothelium, 27 LMP, 28 LGPUC, and 15 high-grade papillary urothelial carcinoma (HGPUC). This was followed by a blinded independent review of the urine cytology specimens by three observers. Each cytology case was marked as negative, atypical, suspicious, or positive for malignant cells by using previously published cytologic criteria. When the negative and atypical diagnoses were grouped together as "benign" and the suspicious and malignant diagnoses as "malignant," the detection rate of "malignancy" of the lesions was as follows: LMP, 37%; LGPUC, 25%; and HGPUC, 53%. The false positive rate was 6%, and the positive predictive value (PPV) was 94%. Detection rates of cells that were at least "atypical" were as follows: LMP, 74%; LGPUC, 79%; and HGPUC, 100%. While most of the LMP and LGPUC cases yielded cells that were at least "atypical," there was no significant difference in the distribution of cytologic diagnoses for LMP and LGPUC cases (P > 0.05). Urine cytology in the context of the 1998 WHO/ISUP classification appears to be useful as a screening tool but does not appear to discriminate LMP effectively from LGPUC. PMID:12672093

Whisnant, Richard E; Bastacky, Sheldon I; Ohori, N Paul



Potential role of septins in oral carcinogenesis: An update and avenues for future research  

PubMed Central

Septins belong to the GTPase superclass of conserved proteins and have been identified to play a role in diverse aspects of cell biology, from cytokinesis to the maintenance of cellular morphology. At least 14 septins have been identified in humans. With their complex patterns in gene expressions and interaction, it has been reported that alterations in septin expression are observed in human diseases. Although much is not known about the role of human septins in oral carcinogenesis, circumstantial evidence does indicate that it may play a major role. This review intends to summarize the basis of septin biology, with the focus being on the evidence for septin involvement in human oral cancer.

Thavarajah, Rooban; Vidya, KM; Joshua, Elizabeth; Rao, Umadevi K; Ranganathan, K



H2S generation and Eh reduction in cysteine challenge testing as a means of determining the potential of test products and treatments for inhibiting oral malodor  

Microsoft Academic Search

Bacterial degradation of the sulfur-containing amino acid, cysteine, involves two biochemical processes that contribute significantly to oral malodor generation. The first is production of hydrogen sulfide, a major component and common indicator of oral malodor formation. The second is generation of the sulfhydryl anion, HS?, an anion that is central to the lowering of the oxidation–reduction potential (Eh). A reduced

I Kleinberg; D Codipilly



The potential role of new oral anticoagulants in the prevention and treatment of thromboembolism  

Microsoft Academic Search

Thromboembolic disorders are among the major causes of morbidity and mortality, and anticoagulation remains the cornerstone of prevention and treatment of these disorders. Although effective, the well-established agents have significant drawbacks. Heparin, low molecular weight heparin, and fondaparinux must be given parenterally, which is inconvenient for long-term or home use. The orally administered vitamin K antagonists (such as warfarin) have

Thomas Mavrakanas; Henri Bounameaux



Modulation of growth and angiogenic potential of oral squamous carcinoma cells in vitro using salvianolic acid B  

PubMed Central

Background Our previous studies showed that Salvianolic acid B (Sal B) inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters and such anti-cancer effects might be related to the inhibition of angiogenesis. This study was aimed to further investigate the anti-proliferative effect of Sal B on the most common type of oral cancer, oral squamous cell carcinoma (OSCC) and the possible mechanisms of action with respect to angiogenesis inhibition. Methods Two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC4, and premalignant leukoplakia cells were treated with different concentrations of Sal B. Cytotoxicity was assessed by MTT assay. cDNA microarray was utilized to evaluate the expression of 96 genes known to be involved in modulating the biological processes of angiogenesis. Real-time reverse transcription-polymerase chain reaction analysis was conducted to confirm the cDNA microarray data. Results Sal B induced growth inhibition in OSCC cell lines but had limited effects on premalignant cells. A total of 17 genes showed a greater than 3-fold change when comparing Sal B treated OSCC cells to the control. Among these genes, HIF-1?, TNF? and MMP9 are specifically inhibited, expression of THBS2 was up-regulated. Conclusions Sal B has inhibitory effect on OSCC cell growth. The antitumor effect can be attributed to anti-angiogenic potential induced by a decreased expression of some key regulator genes of angiogenesis. Sal B may be a promising modality for treating oral squamous cell carcinoma.



Proliferation and apoptosis markers in oral submucous fibrosis  

PubMed Central

Background: Premalignant/potentially malignant-oral lesions and conditions such as oral submucous fibrosis are known to transform into oral cancer. The malignant transformation is often associated with changes at the genetic level that in turn is reflected by the altered expression of proteins related to cell cycle, proliferation, and apoptosis. Aim: To evaluate the expression of p53, Ki67 (MIB), bcl2, and bax in oral submucous fibrosis and oral squamous cell carcinoma. Materials and Methods: To assess the immunohistochemical expression of p53, Ki67 (MIB), bcl2, and bax in 50 cases of oral submucous fibrosis (OSF) and ten each of normal and oral squamous cell carcinoma (OSCC). Results: The labeling indices (LI) of OSF and OSCC were comparable for p53 and Ki67.The p53 LI ranged from 7.9 to 71.9 in OSF and 65.2 to 85.9 in OSCC, and for Ki67 it ranged from 4.39 to 43.23, 18.35 to 42.33, respectively. Conclusion: The p53, Ki67, and bax profiles of OSF and OSCC were altered compared to the normal and these markers could be used as surrogate markers of malignant transformation in OSF.

Ranganathan, K; Kavitha, R



Fused piperidines as a novel class of potent and orally available transient receptor potential melastatin type 8 (TRPM8) antagonists.  


The transient receptor potential melastatin type 8 (TRPM8) is a nonselective cation channel primarily expressed in a subpopulation of sensory neurons that can be activated by a wide range of stimuli, including menthol, icilin, and cold temperatures (<25 °C). Antagonism of TRPM8 is currently under investigation as a new approach for the treatment of pain. As a result of our screening efforts, we identified tetrahydrothienopyridine 4 as an inhibitor of icilin-induced calcium influx in CHO cells expressing recombinant rat TRPM8. Exploration of the structure-activity relationships of 4 led to the identification of a potent and orally bioavailable TRPM8 antagonist, tetrahydroisoquinoline 87. Compound 87 demonstrated target coverage in vivo after oral administration in a rat pharmacodynamic model measuring the prevention of icilin-induced wet-dog shakes (WDS). PMID:22329507

Tamayo, Nuria A; Bo, Yunxin; Gore, Vijay; Ma, Vu; Nishimura, Nobuko; Tang, Phi; Deng, Hong; Klionsky, Lana; Lehto, Sonya G; Wang, Weiya; Youngblood, Brad; Chen, Jiyun; Correll, Tiffany L; Bartberger, Michael D; Gavva, Narender R; Norman, Mark H



Pseudoprogression in patients with malignant gliomas treated with concurrent temozolomide and radiotherapy: potential role of p53  

Microsoft Academic Search

We investigated pseudoprogression (psPD) in patients with malignant gliomas treated with radiotherapy (RT) and maintenance\\u000a temozolomide (TMZ) in terms of incidence, outcomes, and predictive and prognostic factors. We evaluated p53 overexpression\\u000a by immunohistochemical analysis of thirty-five tumor samples as a predictor for psPD. The time to progression and overall\\u000a survival were compared between subgroups, psPD versus early progression (ePD) versus

Hyun-Cheol Kang; Chae-Yong Kim; Jung Ho Han; Ghee Young Choe; Jae Hyoung Kim; Jee Hyun Kim; In Ah Kim



The oxidation states and chemical environments of iron and zinc as potential indicators of brain tumour malignancy grade - preliminary results.  


Despite the enormous advances in medicine, brain tumours are still among the lesser-known types of tumours and carry the worst prognoses. Transition metals are believed to play an essential role in carcinogenesis. The aim of this study was to determine differences in the average oxidation state and trends in the changes in the chemical environment of iron and zinc contained in healthy and neoplastic tissues of the human brain. For this purpose, X-ray Absorption Spectroscopy was used, which enables the study of disordered matter. The samples were taken intraoperatively and then immediately frozen to slow down chemical processes. Sixteen tumour samples with various malignancy grades were studied as well as one control sample. For each sample four to eight spectra were recorded, with a shift between them not greater than 0.2 eV. In all of the samples, iron occurred in compounds with both Fe(2+) and Fe(3+). However, the ratio of Fe(ii) to Fe(iii) content in the tissue visibly increased with the tumour malignancy grade. The change in the oxidation state of iron did not correlate with the hypoxia level of the tissues. Analysis of EXAFS spectra of zinc atoms showed that the chemical environment of zinc atoms differed with the tumour malignancy grade. Additionally, cryogenic conditions were found to produce positive results in studies of biological samples, whose form under such conditions is close to their native state, without preparation-caused artefacts. PMID:23945910

Wandzilak, Aleksandra; Czyzycki, Mateusz; Wrobel, Pawel; Szczerbowska-Boruchowska, Magdalena; Radwanska, Edyta; Adamek, Dariusz; Lankosz, Marek



Caf? Discussions on Oral Sex, Oral Cancer, and HPV Infection: Summative Report  

PubMed Central

Recent emphasis has been placed on the potential links between oral sex, HPV infection, and oral cancer development. Such links were addressed by researchers, clinicians, and the community during two Café Scientifique discussions in October and November 2008, in Vancouver, Canada. The Cafes gathered panels of experts on oral pathology, dentistry, oncology, social work, and community-based research who interacted with an audience of policy makers, health care administrators, sociologists, sexologists, pharmacists, clinical and social researchers, social workers, technicians, and graduate, undergraduate, and high school students. This commentary summarizes the main points discussed during these two events to encourage a worldwide open dialogue about potential risks for oral cancer beyond tobacco smoking and excessive alcohol consumption as such malignancies have high mortality and morbidity, but are yet preventable diseases.



Café discussions on oral sex, oral cancer, and HPV infection: summative report.  


Recent emphasis has been placed on the potential links between oral sex, HPV infection, and oral cancer development. Such links were addressed by researchers, clinicians, and the community during two Café Scientifique discussions in October and November 2008, in Vancouver, Canada. The Cafes gathered panels of experts on oral pathology, dentistry, oncology, social work, and community-based research who interacted with an audience of policy makers, health care administrators, sociologists, sexologists, pharmacists, clinical and social researchers, social workers, technicians, and graduate, undergraduate, and high school students. This commentary summarizes the main points discussed during these two events to encourage a worldwide open dialogue about potential risks for oral cancer beyond tobacco smoking and excessive alcohol consumption as such malignancies have high mortality and morbidity, but are yet preventable diseases. PMID:20054632

Brondani, Mario Augusto



Potential to improve oral health care through evidence, protocols, and payment models.  


Evidence-based health care aims to utilize the best available evidence from scientific methods and apply this evidence to clinical and public health practice. Evidence of the benefits and risks of treatment is derived from randomized controlled clinical trials, systematic reviews, and expert panels. Evidence-based clinical parameters and guidelines should foster the best health outcomes for individuals or populations at reduced costs. By incorporating evidence-based guidelines into payment models, the payers - private or public - have the capacity to improve oral health care and ultimately oral health outcomes. This paper uses examples from pediatric dentistry to show how adoption of caries risk factors, clinical management protocols, and a reimbursement system based on evidence-based guidelines may allow for better quality of care to more individuals and at a lower cost. PMID:22433101

Tinanoff, Norman



Probiotics in oral health--a review.  


Probiotics are dietary supplements containing potentially beneficial bacteria or yeasts. Probiotics are live microorganisms thought to be beneficial to the host organism and, when administered in adequate amounts, confer a health benefit on the host. Lactic acid bacteria and bifidobacteria are the most common types of microbes used as probiotics. Probiotics strengthen the immune system to combat allergies, stress, exposure to toxic substances and other diseases. There are reports of beneficial use in HIV infections and cancers.These products help in stimulating oral health promoting flora, and suppress the pathologic colonization and disease spread. Probiotics can be bacteria, molds and yeast, but most probiotics are bacteria. In recent years, there has been a lot of interest in the use of probiotics in maintaining good oral health and treating oral infections. Their use in premalignant and malignant oral disorders is yet to be probed. PMID:22866427

Rao, Yadav; Lingamneni, Benhur; Reddy, Deepika



Liposomes containing glycocholate as potential oral insulin delivery systems: preparation, in vitro characterization, and improved protection against enzymatic degradation  

PubMed Central

Background: Oral delivery of insulin is challenging and must overcome the barriers of gastric and enzymatic degradation as well as low permeation across the intestinal epithelium. The present study aimed to develop a liposomal delivery system containing glycocholate as an enzyme inhibitor and permeation enhancer for oral insulin delivery. Methods: Liposomes containing sodium glycocholate were prepared by a reversed-phase evaporation method followed by homogenization. The particle size and entrapment efficiency of recombinant human insulin (rhINS)-loaded sodium glycocholate liposomes can be easily adjusted by tuning the homogenization parameters, phospholipid:sodium glycocholate ratio, insulin:phospholipid ratio, water:ether volume ratio, interior water phase pH, and the hydration buffer pH. Results: The optimal formulation showed an insulin entrapment efficiency of 30% ± 2% and a particle size of 154 ± 18 nm. A conformational study by circular dichroism spectroscopy and a bioactivity study confirmed the preserved integrity of rhINS against preparative stress. Transmission electron micrographs revealed a nearly spherical and deformed structure with discernable lamella for sodium glycocholate liposomes. Sodium glycocholate liposomes showed better protection of insulin against enzymatic degradation by pepsin, trypsin, and ?-chymotrypsin than liposomes containing the bile salt counterparts of sodium taurocholate and sodium deoxycholate. Conclusion: Sodium glycocholate liposomes showed promising in vitro characteristics and have the potential to be able to deliver insulin orally.

Niu, Mengmeng; Lu, Yi; Hovgaard, Lars; Wu, Wei



Malignant Melanoma  

PubMed Central

The diagnosis of malignant melanoma does not necessarily imply a grave prognosis. If the tumor is superficial, the chances of surgical cure may be good. Virtually all malignant melanoma arise from junctional nevi. Most nevi of the palms, soles, and genitalia are junctional nevi, therefore prophylactic excision of these nevi is recommended. The surgical treatment of malignant melanoma involves a wide excision and usually skin graft reconstruction. Chemotherapy and immunotherapy are used as adjuncts in the treatment of disseminated disease.

Birdsell, D. S.



The therapeutic potential of inhibitors of the signal transducer and activator of transcription 3 for central nervous system malignancies  

PubMed Central

Background: High-grade primary and metastatic central nervous system (CNS) tumors are common, deadly, and refractory to conventional therapy and continue to be therapeutically challenging. A key nodal transcriptional factor, the signal transducer and activator of transcription 3 (STAT3), drives the fundamental components of tumor malignancy and metastases in the CNS by enhancing proliferation, angiogenesis, invasion, metastasis, and immunosuppression. The introduction of STAT3 inhibitors in clinical trials for this patient population is imminent. Methods: STAT3 inhibitors have been extensively tested in a variety of preclinical murine models. Results: The STAT3 inhibitor, WP1066, has displayed marked efficacy with minimal toxicity against malignancy in murine models, including established intracerebral tumors. The mechanism of this in vivo efficacy of the STAT3 blockade agents is a combination of direct tumor cytotoxicity and immune cytotoxic clearance. Conclusions: Given their direct antitumor cytotoxic effects, STAT3 inhibitors may exert therapeutic activity in the monotherapy setting but may also have compelling use as immunotherapeutic modulators or as a salvage therapy.

Heimberger, Amy B.



Is the NBN gene mutation I171V a potential risk factor for malignant solid tumors in children?  


NBN gene is considered as one of the low-to-moderate cancer susceptibility gene. At least 4 germline NBN mutations have been found in several malignancies in adults. In our studies, we observed the high incidence of germline mutation I171V of NBN gene in breast, colorectal, larynx cancer, and in multiple primary tumors. In this study, we would like to answer the question whether I171V germline mutation of NBN gene may constitute risk factor for solid tumors in children. The frequency of this mutation has been analyzed in patients with neuroblastoma (n=66), Wilms tumor (n=54), medulloblastoma (n=57), and rhabdomyosarcoma (n=82) hospitalized in Pediatric Oncology, Hematology and Bone Marrow Transplantation Department in the years between 1987 and 2010. About 2947 anonymous blood samples collected on Guthrie cards drawn from the newborn screening program of the Wielkopolska region have been used as controls. All the patients and controls came from the same geographical region. I171V mutation of the NBN gene has been observed in 5 controls. Among children with solid tumors only in 1 child with medulloblastoma I171V variant has been found. In conclusion, I171V germline mutation in contrary to adults cannot be considered as a risk factor for children malignancies. However, owing to low number of patients with solid tumors the possibility of a Type II error may exist. PMID:21436738

Nowak, Jerzy; Mosor, Maria; Nowicka, Karina; Rembowska, Jolanta; Januszkiewicz, Danuta



Traditional Medicinal Plant Extracts and Natural Products with Activity against Oral Bacteria: Potential Application in the Prevention and Treatment of Oral Diseases  

PubMed Central

Oral diseases are major health problems with dental caries and periodontal diseases among the most important preventable global infectious diseases. Oral health influences the general quality of life and poor oral health is linked to chronic conditions and systemic diseases. The association between oral diseases and the oral microbiota is well established. Of the more than 750 species of bacteria that inhabit the oral cavity, a number are implicated in oral diseases. The development of dental caries involves acidogenic and aciduric Gram-positive bacteria (mutans streptococci, lactobacilli and actinomycetes). Periodontal diseases have been linked to anaerobic Gram-negative bacteria (Porphyromonas gingivalis, Actinobacillus, Prevotella and Fusobacterium). Given the incidence of oral disease, increased resistance by bacteria to antibiotics, adverse affects of some antibacterial agents currently used in dentistry and financial considerations in developing countries, there is a need for alternative prevention and treatment options that are safe, effective and economical. While several agents are commercially available, these chemicals can alter oral microbiota and have undesirable side-effects such as vomiting, diarrhea and tooth staining. Hence, the search for alternative products continues and natural phytochemicals isolated from plants used as traditional medicines are considered as good alternatives. In this review, plant extracts or phytochemicals that inhibit the growth of oral pathogens, reduce the development of biofilms and dental plaque, influence the adhesion of bacteria to surfaces and reduce the symptoms of oral diseases will be discussed further. Clinical studies that have investigated the safety and efficacy of such plant-derived medicines will also be described.

Palombo, Enzo A.



Human papillomavirus infections and oral tumors.  


In the past 20 years, there has been an increasing interest in human papillomaviruses (HPV) because of their potential role in the pathogenesis of malignant tumors. In 1983, we published the first evidence that HPV might be involved in oral squamous cell carcinomas. The identification of morphological similarities between oral and cervical mucosa lead us to this original proposal. In a recent meta-analysis, HPV was indeed confirmed as an independent risk factor for oral carcinoma. To date, totally more than 100 types of HPV have been identified. As in anogenital cancers, HPV type 16 is the most prevalent type in oral carcinomas. The benign oral lesions, associated with HPV infection, include squamous cell papilloma, condyloma acuminatum, verrucca vulgaris and focal epithelial hyperplasia (FEH). Papillomas and condylomas are mostly caused by HPV type 6 or 11, while oral verrucas are associated with the skin types 2 or 4. A family history of FEH has been suggested. The FEH lesions are caused by HPV types 13 and 32, only detected in oral epithelium. In immunocompromised patients, benign HPV-induced lesions are characterized by atypical morphology and the simultaneous detection of multiple HPV types. Oral benign HPV lesions are mostly asymptomatic, and may persist or regress spontaneously. PMID:12920585

Syrjänen, Stina



Efficacy of benzydamine hydrochloride, chlorhexidine, and povidone iodine in the treatment of oral mucositis among patients undergoing radiotherapy in head and neck malignancies: A drug trail  

PubMed Central

Background and Objectives: Oral mucositis is a common and debilitating complication of radiotherapy, which is associated with significant morbidity. It is therefore extremely important that mucositis be prevented, or at least treated to reduce its severity and sequelae. The objective of the study was to manage oral mucositis induced by radiotherapy and to reduce pain by using Benzydamine hydrochloride (0.15%), Chlorhexidine (0.2%), and Povidone iodine (5%). Results: Benzydamine hydrochloride was observed to be effective and delayed the development of severe form of mucositis and appears more efficient in the management of radiation-induced mucositis. Conclusion: Benzydamine hydrochloride (0.15%) is safe, well tolerated, helps not just in delaying the progression of mucositis but also reduces the intensity of pain.

Roopashri, G.; Jayanthi, K.; Guruprasad, R.



A potential link between oral status and hearing impairment: preliminary observations.  


Some previous studies suggest an association between tooth loss and hearing loss. The aim of this study is to assess the relation between oral status and hearing acuity. Forty-eight patients (mean age: 64.7 years) were allocated to four groups: one was wearing complete dentures in both jaws, another had shortened dental arches, a third had full dental arches in both jaws and the last lacked any occlusal stops (i.e. no occlusal vertical dimension, because of the absence of teeth or occlusal pairs). Audiological testing was performed in a noise-free chamber. Air and bone conduction were checked at different frequencies and the air-bone gap was determined. After correction for age and gender, a difference in air and bone conduction because of the oral status was found for low and for high frequencies while no significant differences were (P < 0.05) found for the air-bone gap. The number of teeth, number of occluding tooth pairs and presence or lack of occlusal vertical dimension, was significantly related to the gradient of hearing loss (P < 0.05). The discrepancy in hearing loss between complete denture wearers and patients without any occlusal vertical dimension, strengthens the hypothesis that it is the lack of the latter that is associated with hearing loss. At what level hearing loss occurs, needs further investigation. PMID:15089934

Peeters, J; Naert, I; Carette, E; Manders, E; Jacobs, R



Protein O-fucosyltransferase 1: A potential diagnostic marker and therapeutic target for human oral cancer.  


Protein O-fucosyltransferase 1 (POFUT1) is the enzyme that adds O-fucose through O-glycosidic linkage to conserved serine or threonine residues in the epidermal growth factor-like repeats of a number of cellular surface and secreted proteins. Our previous study using microarray technology showed that significant upregulation of POFUT1 occurs in oral squamous cell carcinoma (OSCC)-derived cell lines compared to human normal oral keratinocytes. The aim of the present study was to examine the status of POFUT1 mRNA and protein expression in OSCC-derived cell lines and human primary OSCCs. POFUT1 mRNA was upregulated significantly (P<0.05 for both comparisons) in five OSCC-derived cell lines and primary OSCCs using quantitative reverse transcriptase-polymerase chain reaction. Immunohistochemistry data indicated that POFUT1 protein expression levels were consistent with mRNA expression status in OSCC-derived cell lines and primary OSCCs. Furthermore, POFUT1 expression status was correlated significantly (P=0.048) with the primary tumor size. The proliferation of POFUT1 knockdown cells was inhibited significantly compared with that of control cells. These results indicated that POFUT1 expression can contribute to cancer progression and that POFUT1 may serve as a diagnostic marker and a therapeutic target for OSCCs. PMID:24064921

Yokota, Satoshi; Ogawara, Katsunori; Kimura, Ryota; Shimizu, Fumie; Baba, Takao; Minakawa, Yasuyuki; Higo, Morihiro; Kasamatsu, Atsushi; Endo-Sakamoto, Yosuke; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro



Antiherpetic potential of 6-bromoindirubin-3'-acetoxime (BIO-acetoxime) in human oral epithelial cells.  


Glycogen synthase kinase 3 (GSK-3) functions in the regulation of glycogen metabolism, in the cell cycle, and in immune responses and is targeted by some viruses to favor the viral life cycle. Inhibition of GSK-3 by 6-bromoindirubin-3'-acetoxime (BIO-acetoxime), a synthetic derivative of a compound from the Mediterranean mollusk Hexaplex trunculus, protects cells from varicella infection. In this study, we examined the effects of BIO-acetoxime against herpes simplex virus-1 (HSV-1) infection in human oral epithelial cells, which represent a natural target cell type. The results revealed that BIO-acetoxime relieves HSV-1-induced cytopathic effects and apoptosis. We also found that BIO-acetoxime reduced viral yields and the expression of different classes of viral proteins. Furthermore, addition of BIO-acetoxime before, simultaneously with or after HSV-1 infection significantly reduced viral yields. Collectively, BIO-acetoxime may suppress viral gene expression and protect oral epithelial cells from HSV-1 infection. These results suggest the possible involvement of GSK-3 in HSV-1 infection. PMID:23392633

Hsu, Mei-Ju; Hung, Shan-Ling



Potential side effects of dental amalgam restorations. (I). An oral and medical investigation.  


The aim of this study was to explore a possible association between health status and self-reported adverse effects related to dental amalgam restorations. A group of 50 consecutive patients (index group), referred for complaints self-related to dental amalgam restorations, was compared with a control group of individuals matched by age, sex and postal zip code. The patients underwent an oral, stomatognathic, medical and clinical chemistry examination. Mercury levels were examined in blood, urine and hair. The results revealed that somatic diseases were more common in the index group (38% versus 6%). Symptoms related to cranio-mandibular dysfunction were reported by 74% of the patients in the index group versus 24% in the control group, and were diagnosed in 62% and 36%, respectively. The oral health status and the number of amalgam surfaces were similar in the 2 groups. No positive skin patch test to mercury was found in any of the groups. The estimated mercury intake from fish consumption, occupational exposure, and mercury levels in blood and urine were also similar and far below levels, where negative health effects would be expected. The correlation between the number of amalgam surfaces and mercury levels in plasma and urine (r=0.43) indicated a release of mercury from dental amalgam restorations in both groups. Since the mercury levels were similar among index patients and controls, mercury was not a likely cause of the impaired health reported by the patients. PMID:9249190

Bratel, J; Haraldson, T; Meding, B; Yontchev, E; Ohman, S C; Ottosson, J O



Immunohistochemical determination of HER-2/neu overexpression in malignant melanoma reveals no prognostic value, while c-Kit (CD117) overexpression exhibits potential therapeutic implications  

PubMed Central

Background HER-2/neu and c-kit (CD117) onco-protein are increasingly being recognized as targets for therapy in solid tumors, but data on their role in malignant melanoma is currently limited. We studied the prevalence of overexpression of HER-2/neu and c-Kit in 202 patients with malignant melanoma to evaluate a possible prognostic value of these molecular targets in malignant melanoma. Methods Overexpression of HER-2/neu and c-Kit was evaluated using immunohistochemical assays in 202 archival tissue specimens. Results Between 1991 and 2001, 202 subjects (109 males; 54% and 93 females; 46%) with malignant melanoma were studied with a mean age of 57 years (age range: 15–101 years). The most common histologic type was amelanotic melanoma (n = 62; 30.7%) followed by superficial spreading melanoma (n = 54; 26.7%). The depth of penetration of melanoma (Breslow thickness, pT Stage) ranged from 0.4 mm (stage pT1) to 8.0 mm (stage pT4A). Mean thickness was 2.6 mm (stage pT3A). The ECOG performance scores ranged from 0 to 3. Only 2 patients (0.9%) revealed HER-2/neu overexpression, whereas 46 (22.8%) revealed c-Kit overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit positive and negative groups (p = 0.36). Interestingly, not only was c-Kit more likely to be overexpressed in the superficial spreading type, a preliminary association between the presence or absence of c-Kit overexpression and the existence of another second primary tumor was also observed. Conclusions The results of our large study indicate that the HER-2/neu onco-protein neither has a role in melanogenesis nor is a potential target for clinical trials with monoclonal antibody therapy. This indicates there is no role for its testing in patients with malignant melanoma. Although c-Kit, expressed preferentially in the superficial spreading type, may not have prognostic value, it does have significant therapeutic implications as a molecular target warranting further investigation.

Potti, Anil; Hille, Rachel C; Koch, Michael



Applications of OralCDx (R) methodology in the diagnosis of oral leukoplakia  

PubMed Central

Objective: We aim to evaluate the effectiveness of the brush biopsy technique using OralCDx ® (OralScan Laboratories Inc., Suffern, NY) as a new method for early diagnosis and control of a “potentially malignant disorder” such as oral leukoplakia. Design of the study: We performed a study in which samples were taken using OralCDx ® on 24 patients who visited the Master of Oral Medicine, Oral Surgery and Implantology of the University of Santiago de Compostela between February 2009 and May 2010. These patients presented clinical and histological lesions that were consistent with oral leukoplakia. We evaluated the relationship between the keratinization degree of the lesions and cell representation; the diagnosis obtained through OralCDx ® and biopsies; and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results: 50% of patients were men and 50% women with an average age of 62.38 years. The Kappa coefficient relating keratinization of lesions and cell representation was 0.33, the OralCDx ® - biopsy diagnostic rate reached a Kappa value of 0.66, recording 72.7%,sensitivity and 92.3% specificity, PPV was 88.8%, while NPV reached 80%. Conclusions: cytology sampling with OralCDx ® showed high sensitivity and specificity values, which make it a good tool for monitoring oral leukoplakia, but nowadays the most reliable method that allows us to confirm the exact diagnosis of the lesions and their anatomical and pathological characteristics still is conventional biopsy using a surgical scalpel. Key words: OralCDx®, brush biopsy, oral leukoplakia.

Garcia-Carnicero, Tamara; Gandara-Vila, Pilar; Couso-Folgueiras, Elena; Perez-Sayans, Mario; Gandara-Vila, Rafael; Garcia-Garcia, Abel; Gandara-Rey, Jose-Manuel



Interleukin-1 beta in unstimulated whole saliva is a potential biomarker for oral squamous cell carcinoma.  


The objective of this study was to evaluate cytokines in unstimulated whole saliva (UWS) of oral squamous cell carcinoma (OSCC) patients as compared to those with pre- and post-operation for evaluation as markers of OSCC. Sixteen OSCC patients were included in this study. Cytokine concentrations in resting saliva were measured using a Bio-Plex suspension array system. Only interleukin-1 (IL-1) beta showed significantly different cytokine concentration in saliva between pre- and post-operation. IL-1 beta was released from cultured OSCC cells confirmed by ELISA and immunohistochemistry. From this study, IL-1 beta in UWS may be useful for detection of early stage OSCC. More studies are needed to accept the utility of IL-1 beta in UWS for predicting, diagnosis and evaluation of OSCC. PMID:24063998

Kamatani, T; Shiogama, S; Yoshihama, Y; Kondo, S; Shirota, T; Shintani, S



Mutagenesis and carcinogenesis induced by dibenzo[a,l]pyrene in the mouse oral cavity: a potential new model for oral cancer  

PubMed Central

Cancer of the oral cavity is a serious disease, affecting about 30,000 individuals in US annually. There are several animal models of oral cancer, but each has certain disadvantages. As a new model, we investigated whether topical application of the tobacco smoke carcinogen, dibenzo[a,l]pyrene (DB[a,l]P) is mutagenic and carcinogenic in the oral cavity of the B6C3F1 lacI and B6C3F1 mouse, respectively. B6C3F1 lacI mice received DB[a,l]P (0, 3, 6, 12 nmol) 3× per week. B6C3F1 mice received the same doses and also 24 nmol. At 38 weeks mutagenesis was measured in oral tissues in lacI mice. For the high dose group, the mutant fraction (MF) in upper mucosa and tongue increased about twofold relative to that in vehicle-alone. The increases were statistically significant. The mutational profile in the DB[a,l]P-induced mutants was compared with that induced by benzo[a]pyrene (BaP) in oral tissue. BaP is mutagenic in many tissues when administered by gavage. The mutational profile for DB[a,l]P was more similar to that reported for p53 mutations in head and neck cancers than was that of BaP. At 47 weeks, oral squamous cell carcinomas (OSCC) were found in 31% of the high-dose B6C3F1 group. Elevations of p53 and COX-2 protein were observed in tumor and dysplastic tissue. As DB[a,l]P induces mutations and tumors in the oral cavity, and has a mutational profile in oral tissue similar to that found in p53 in human OSCC, the treatment protocol described here may represent a new and relevant model for cancer of the oral cavity.

Guttenplan, Joseph B.; Kosinska, Wieslawa; Zhao, Zhong-Lin; Chen, Kun-Ming; Aliaga, Cesar; DelTondo, Joseph; Cooper, Timothy; Sun, Yuan-Wan; Zhang, Shang-Min; Jiang, Kun; Bruggeman, Richard; Sharma, Arun K.; Amin, Shantu; Ahn, Kwangmi; El-Bayoumy, Karam



Recurrent Chromosomal Imbalances Detected in Biopsy Material from Oral Premalignant and Malignant Lesions by Combined Tissue Microdissection, Universal DNA Amplification, and Comparative Genomic Hybridization  

PubMed Central

Biopsies routinely performed for the histopathological diagnosis of oral epithelial lesions before treatment were screened for chromosomal imbalances by comparative genomic hybridization. Comparative genomic hybridization was performed on 12 oral premalignant lesions (OPLs; dysplasias and carcinomas in situ) and 14 oral squamous cell carcinomas (OSCCs). Eight biopsies displayed areas of different histopathological appearance, so that OPLs and OSCCs from the same patient were analyzed. To avoid contamination with nonneoplastic cells, defined cell populations were isolated by micromanipulation with a glass needle. Before comparative genomic hybridization analysis, universal DNA amplification was performed using the DOP-polymerase chain reaction protocol. In the 14 OSCCs examined, the average number of chromosomal imbalances was significantly higher than in the 12 OPLs (mean ± SEM: 11.9 ± 1.9 versus 3.2 ± 1.2; P = 0.003). The DNA copy number changes identified in more than one OPL were gains on 8q (3 of 12) and 16p (2 of 12), as well as losses on 3p (5 of 12); 5q (4 of 12); 13q (3 of 12); and 4q, 8p, and 9p (2 of 12 each). In more than 30% of OSCCs, gains of chromosomal material were identified on 20q (8 of 14); 8q, 11q, 22q (7 of 14 each); 3q, 15q, and 17p (6 of 14 each); and 14q, 17q, and 20p (5 of 14 each), and losses were identified on 3p and 4q (9 of 14 each), 5q (7 of 14), 13q (6 of 14), and 2q and 9p (5 of 14 each). These results were validated by positive and negative control comparative genomic hybridization experiments and microsatellite analysis for the detection of allelic loss. The vast majority of genomic alterations found in OPLs were again identified in OSCCs from the same biopsy, supporting the hypothesis that multiple lesions in the same patient are clonally related. In summary, we show that comprehensive information on the genomic alterations in oral epithelial lesions can be obtained from small biopsies. Such data may identify prognostic indicators that could eventually assist in designing therapeutic strategies.

Weber, Ruthild G.; Scheer, Martin; Born, I. Antonio; Joos, Stefan; Cobbers, J. M. J. Ludwig; Hofele, Christof; Reifenberger, Guido; Zoller, Joachim E.; Lichter, Peter



Procaine in Malignant Hyperpyrexia  

Microsoft Academic Search

The caffeine contracture of normal human muscle, which has been used as a model for malignant hyperpyrexia, is greatly potentiated by halothane. Prior administration of procaine markedly reduces the halothane-potentiated caffeine contracture, and procaine given at the height of the contracture induces relaxation. Lignocaine, on the other hand, produces a variable response and sometimes increases the contracture.The muscle from a

R. F. W. Moulds; M. A. Denborough



Appraisal of the sensitising potential of orally and dermally administered Mercaptobenzothiazol by a biphasic protocol of the local lymph node assay  

Microsoft Academic Search

Mercaptobenzothiazole (MBT) is used while manufacturing natural rubber products. Our study deals with assessing its allergenic\\u000a potential following dermal and oral routes of exposure, using a biphasic local lymph node assay (LLNA). Female Balb\\/c mice\\u000a were treated with MBT (dermally 3, 10, 30% concentrations in DMSO; orally 1, 10, 100 mg\\/kg doses in corn oil) on the back\\u000a (dermal study) or

Varun Ahuja; Reinhard Wanner; Thomas Platzek; Ralf Stahlmann



Perifosine as a Potential Novel Anti-Cancer Agent Inhibits EGFR/MET-AKT Axis in Malignant Pleural Mesothelioma  

PubMed Central

Background PI3K/AKT signalling pathway is aberrantly active and plays a critical role for cell cycle progression of human malignant pleural mesothelioma (MMe) cells. AKT is one of the important cellular targets of perifosine, a novel bio-available alkylphospholipid that has displayed significant anti-proliferative activity in vitro and in vivo in several human tumour model systems and is currently being tested in clinical trials. Methods We tested Perifosine activity on human mesothelial cells and different mesothelioma cell lines, in order to provide evidence of its efficacy as single agent and combined therapy. Results We demonstrate here that perifosine, currently being evaluated as an anti-cancer agent in phase 1 and 2 clinical trials, caused a dose-dependent reduction of AKT activation, at concentrations causing MMe cell growth arrest. In this study we firstly describe that MMe cells express aside from AKT1 also AKT3 and that either the myristoylated, constitutively active, forms of the two proteins, abrogated perifosine-mediated cell growth inhibition. Moreover, we describe here a novel mechanism of perifosine that interferes, upstream of AKT, affecting EGFR and MET phosphorylation. Finally, we demonstrate a significant increase in cell toxicity when MMe cells were treated with perifosine in combination with cisplatin. Conclusions This study provides a novel mechanism of action of perifosine, directly inhibiting EGFR/MET-AKT1/3 axis, providing a rationale for a novel translational approach to the treatment of MMe.

Pinton, Giulia; Manente, Arcangela Gabriella; Angeli, Giovanni



Preclinical Demonstration of Synergistic Active Nutrients/Drug (AND) Combination as a Potential Treatment for Malignant Pleural Mesothelioma  

PubMed Central

Malignant pleural mesothelioma (MPM) is a poor prognosis disease lacking adequate therapy. We have previously shown that ascorbic acid administration is toxic to MPM cells. Here we evaluated a new combined therapy consisting of ascorbate/epigallocatechin-3-gallate/gemcitabine mixture (called AND, for Active Nutrients/Drug). In vitro effects of AND therapy on various MPM cell lines revealed a synergistic cytotoxic mechanism. In vivo experiments on a xenograft mouse model for MPM, obtained by REN cells injection in immunocompromised mice, showed that AND strongly reduced the size of primary tumor as well as the number and size of metastases, and prevented abdominal hemorrhage. Kaplan Meier curves and the log-rank test indicated a marked increase in the survival of AND-treated animals. Histochemical analysis of dissected tumors showed that AND induced a shift from cell proliferation to apoptosis in cancer cells. Lysates of tumors from AND-treated mice, analyzed with an antibody array, revealed decreased TIMP-1 and -2 expressions and no effects on angiogenesis regulating factors. Multiplex analysis for signaling protein phosphorylation exhibited inactivation of cell proliferation pathways. The complex of data showed that the AND treatment is synergistic in vitro on MPM cells, and blocks in vivo tumor progression and metastasization in REN-based xenografts. Hence, the AND combination is proposed as a new treatment for MPM.

Martinotti, Simona; Gallo, Simone; Russo, Maria Veronica; Mutti, Luciano; Biffo, Stefano; Burlando, Bruno



In-vitro suppression of metabolic activity in malignant human glioblastomas due to pulsed - low frequency electric potential exposures  

NASA Astrophysics Data System (ADS)

The role of pulsed - low repetition frequency electric potential was investigated in suppressing the metabolic activities of aggressive human brain cancer cells. Twenty four hours post exposure the glioblastomas were found to be significantly inhibited in their metabolic activity. The findings herein reveal a near complete inhibition of glioblastoma's metabolic activity through selective applications of low frequency pulsed electric potentials.

Schlichting, Abby; Waynant, Ronald W.; Tata, Darrell B.



Claudin-3 Overexpression Increases the Malignant Potential of Colorectal Cancer Cells: Roles of ERK1/2 and PI3K-Akt as Modulators of EGFR signaling  

PubMed Central

The altered expressions of claudin proteins have been reported during the tumorigenesis of colorectal cancer. However, the molecular mechanisms that regulate these events in this cancer type are poorly understood. Here, we report that epidermal growth factor (EGF) increases the expression of claudin-3 in human colorectal adenocarcinoma HT-29 cells. This increase was related to increased cell migration and the formation of anchorage-dependent and anchorage-independent colonies. We further showed that the ERK1/2 and PI3K-Akt pathways were involved in the regulation of these effects because specific pharmacological inhibition blocked these events. Genetic manipulation of claudin-1 and claudin-3 in HT-29 cells showed that the overexpression of claudin-1 resulted in decreased cell migration; however, migration was not altered in cells that overexpressed claudin-3. Furthermore, the overexpression of claudin-3, but not that of claudin-1, increased the tight junction-related paracellular flux of macromolecules. Additionally, an increased formation of anchorage-dependent and anchorage-independent colonies were observed in cells that overexpressed claudin-3, while no such changes were observed when claudin-1 was overexpressed. Finally, claudin-3 silencing alone despite induce increase proliferation, and the formation of anchoragedependent and -independent colonies, it was able to prevent the EGF-induced increased malignant potential. In conclusion, our results show a novel role for claudin-3 overexpression in promoting the malignant potential of colorectal cancer cells, which is potentially regulated by the EGF-activated ERK1/2 and PI3K-Akt pathways.

de Souza, Waldemir F.; Fortunato-Miranda, Natalia; Robbs, Bruno K.; de Araujo, Wallace M.; de-Freitas-Junior, Julio C.; Bastos, Lilian G.; Viola, Joao P. B.; Morgado-Diaz, Jose A.



Claudin-3 Overexpression Increases the Malignant Potential of Colorectal Cancer Cells: Roles of ERK1/2 and PI3K-Akt as Modulators of EGFR signaling.  


The altered expressions of claudin proteins have been reported during the tumorigenesis of colorectal cancer. However, the molecular mechanisms that regulate these events in this cancer type are poorly understood. Here, we report that epidermal growth factor (EGF) increases the expression of claudin-3 in human colorectal adenocarcinoma HT-29 cells. This increase was related to increased cell migration and the formation of anchorage-dependent and anchorage-independent colonies. We further showed that the ERK1/2 and PI3K-Akt pathways were involved in the regulation of these effects because specific pharmacological inhibition blocked these events. Genetic manipulation of claudin-1 and claudin-3 in HT-29 cells showed that the overexpression of claudin-1 resulted in decreased cell migration; however, migration was not altered in cells that overexpressed claudin-3. Furthermore, the overexpression of claudin-3, but not that of claudin-1, increased the tight junction-related paracellular flux of macromolecules. Additionally, an increased formation of anchorage-dependent and anchorage-independent colonies were observed in cells that overexpressed claudin-3, while no such changes were observed when claudin-1 was overexpressed. Finally, claudin-3 silencing alone despite induce increase proliferation, and the formation of anchoragedependent and -independent colonies, it was able to prevent the EGF-induced increased malignant potential. In conclusion, our results show a novel role for claudin-3 overexpression in promoting the malignant potential of colorectal cancer cells, which is potentially regulated by the EGF-activated ERK1/2 and PI3K-Akt pathways. PMID:24069372

de Souza, Waldemir F; Fortunato-Miranda, Natalia; Robbs, Bruno K; de Araujo, Wallace M; de-Freitas-Junior, Julio C; Bastos, Lilian G; Viola, João P B; Morgado-Díaz, José A



Pathogenesis and therapeutic intervention of oral submucous fibrosis.  


Oral submucous fibrosis (OSF) is a chronic, progressive, potentially malignant condition affecting the oral cavity and frequently involving the upper part of the aerodigestive tract including the oropharynx and the upper part of the esophagus. It is characterized by juxtaepithelial inflammatory reaction and progressive fibrosis of lamina propria, leading to stiffening of the oral mucosa eventually causing trismus. This condition is associated with significant morbidity and high risk of malignancy. Over the years, several drugs and combinations have been tried for the treatment of submucous fibrosis, but with limited success, because of its unclear molecular pathogenesis. Till date, there are no known effective treatments for OSF. The aim of this article is to emphasize on the molecular changes taking place in OSF and possible therapeutic interventions. PMID:23946584

Yoithapprabhunath, Thukanaykanpalayam Ragunathan; Maheswaran, Thangadurai; Dineshshankar, Janardhanam; Anusushanth, Abraham; Sindhuja, Pandian; Sitra, Govindasamy



Pathogenesis and therapeutic intervention of oral submucous fibrosis  

PubMed Central

Oral submucous fibrosis (OSF) is a chronic, progressive, potentially malignant condition affecting the oral cavity and frequently involving the upper part of the aerodigestive tract including the oropharynx and the upper part of the esophagus. It is characterized by juxtaepithelial inflammatory reaction and progressive fibrosis of lamina propria, leading to stiffening of the oral mucosa eventually causing trismus. This condition is associated with significant morbidity and high risk of malignancy. Over the years, several drugs and combinations have been tried for the treatment of submucous fibrosis, but with limited success, because of its unclear molecular pathogenesis. Till date, there are no known effective treatments for OSF. The aim of this article is to emphasize on the molecular changes taking place in OSF and possible therapeutic interventions.

Yoithapprabhunath, Thukanaykanpalayam Ragunathan; Maheswaran, Thangadurai; Dineshshankar, Janardhanam; Anusushanth, Abraham; Sindhuja, Pandian; Sitra, Govindasamy



Oral candidiasis  

PubMed Central

Oral candidiasis is a common opportunistic infection of the oral cavity caused by an overgrowth of Candida species, the commonest being Candida albicans. The incidence varies depending on age and certain predisposing factors. There are three broad groupings consisting of acute candidiasis, chronic candidiasis, and angular cheilitis. Risk factors include impaired salivary gland function, drugs, dentures, high carbohydrate diet, and extremes of life, smoking, diabetes mellitus, Cushing's syndrome, malignancies, and immunosuppressive conditions. Management involves taking a history, an examination, and appropriate antifungal treatment with a few requiring samples to be taken for laboratory analysis. In certain high risk groups antifungal prophylaxis reduces the incidence and severity of infections. The prognosis is good in the great majority of cases.

Akpan, A; Morgan, R



Diagnostic aids in the screening of oral cancer  

PubMed Central

The World Health Organization has clearly indentified prevention and early detection as major objectives in the control of the oral cancer burden worldwide. At the present time, screening of oral cancer and its pre-invasive intra-epithelial stages, as well as its early detection, is still largely based on visual examination of the mouth. There is strong available evidence to suggest that visual inspection of the oral mucosa is effective in reducing mortality from oral cancer in individuals exposed to risk factors. Simple visual examination, however, is well known to be limited by subjective interpretation and by the potential, albeit rare, occurrence of dysplasia and early OSCC within areas of normal-looking oral mucosa. As a consequence, adjunctive techniques have been suggested to increase our ability to differentiate between benign abnormalities and dysplastic/malignant changes as well as to identify areas of dysplasia/early OSCC that are not visible to naked eye. These include the use of toluidine blue, brush biopsy, chemiluminescence and tissue autofluorescence. The present paper reviews the evidence supporting the efficacy of the aforementioned techniques in improving the identification of dysplastic/malignant changes of the oral mucosa. We conclude that available studies have shown promising results, but strong evidence to support the use of oral cancer diagnostic aids is still lacking. Further research with clear objectives, well-defined population cohorts, and sound methodology is strongly required.

Fedele, Stefano



Revisiting the association between candidal infection and carcinoma, particularly oral squamous cell carcinoma  

PubMed Central

Background Tobacco and alcohol are risk factors associated with cancer of the upper aerodigestive tract, but increasingly the role of infection and chronic inflammation is recognized as being significant in cancer development. Bacteria, particularly Helicobacter pylori, and viruses such as members of the human papilloma virus family and hepatitis B and C are strongly implicated as etiological factors in certain cancers. There is less evidence for an association between fungi and cancer, although it has been recognized for many years that white patches on the oral mucosa, which are infected with Candida, have a greater likelihood of undergoing malignant transformation than those that are not infected. Objective This article reviews the association between the development of oral squamous cell carcinoma in potentially malignant oral lesions with chronic candidal infection and describes mechanisms that may be involved in Candida-associated malignant transformation.

Mohd Bakri, Marina; Mohd Hussaini, Haizal; Rachel Holmes, Ann; David Cannon, Richard; Mary Rich, Alison



Evaluating the acute effects of oral, non-combustible potential reduced exposure products marketed to smokers  

Microsoft Academic Search

BackgroundNon-combustible potential reduced exposure products (PREPs; eg, Star Scientific's Ariva; a variety of other smokeless tobacco products) are marketed to reduce the harm associated with smoking. This marketing occurs despite an absence of objective data concerning the toxicant exposure and effects of these PREPs. Methods used to examine combustible PREPs were adapted to assess the acute effects of non-combustible PREPs

C. O. Cobb; M. F. Weaver; T. Eissenberg



Oral epithelial dysplasia and squamous cell carcinoma following allogeneic hematopoietic stem cell transplantation: clinical presentation and treatment outcomes.  


Late complications of allogeneic hematopoietic stem cell transplantation (HSCT) include a risk of secondary malignancies. Optimization for early diagnosis and treatment of oral premalignant or malignant lesions requires an assessment of potential predisposing risk factors. The medical records of patients who developed oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) following allogeneic-HSCT were reviewed. Data on HSCT course, chronic graft-versus-host disease (cGVHD), and clinical outcome were recorded; landmark survival was calculated. Twenty-six patients with OED (n=8) and OSCC (n=18) were identified with a median follow-up of 26.5 and 21.5 months, respectively. Premalignant and malignant oral lesions were diagnosed at a median time of 2.5 and 8 years after HSCT, respectively. Chronic GVHD was present in 96% of patients and of these, 96% had oral involvement. Multifocal oral cancer was found in 28% of cases, and localized recurrence was observed in 44% of cases. These results suggest that oral cGVHD may be considered a potential risk factor for the development of OSCC following allogeneic-HSCT. The observation that oral cancers were frequently multifocal and recurred locally suggests that these cancers may be more aggressive. Vigilant follow-up and coordination of care are critical. PMID:21460866

Mawardi, H; Elad, S; Correa, M E; Stevenson, K; Woo, S-B; Almazrooa, S; Haddad, R; Antin, J H; Soiffer, R; Treister, N



Metastases to the oral cavity.  


Metastatic spread to the oral cavity of a malignant neoplasm is a rare yet important sign of advanced systemic malignant disease. This manuscript briefly describes the metastatic process and highlights the most common neoplasms that metastasise to the oral cavity as well as their clinical and radiological presentations. The role of the patients' history in suspecting metastatic disease and the importance of a microscopic diagnosis is emphasised. PMID:23957102

Raubenheimer, E J; Noffke, C E E; Hendrik, H D



Reducing the Risk of Xerostomia and Mandibular Osteoradionecrosis: The Potential Benefits of Intensity Modulated Radiotherapy in Advanced Oral Cavity Carcinoma  

SciTech Connect

Radiation therapy for squamous cell carcinoma of the oral cavity may be curative, but carries a risk of permanent damage to bone, salivary glands, and other soft tissues. We studied the potential of intensity modulated radiotherapy (IMRT) to improve target volume coverage, and normal tissue sparing for advanced oral cavity carcinoma (OCC). Six patients with advanced OCC requiring bilateral irradiation to the oral cavity and neck were studied. Standard 3D conformal radiotherapy (3DCRT) and inverse-planned IMRT dose distributions were compared by using dose-volume histograms. Doses to organs at risk, including spinal cord, parotid glands, and mandible, were assessed as surrogates of radiation toxicity. PTV1 mean dose was 60.8 {+-} 0.8 Gy for 3DCRT and 59.8 {+-} 0.1 Gy for IMRT (p = 0.04). PTV1 dose range was 24.7 {+-} 6 Gy for 3DCRT and 15.3 {+-} 4 Gy for IMRT (p = 0.001). PTV2 mean dose was 54.5 {+-} 0.8 Gy for 3DCRT and for IMRT was 54.2 {+-} 0.2 Gy (p = 0.34). PTV2 dose range was improved by IMRT (7.8 {+-} 3.2 Gy vs. 30.7 {+-} 12.8 Gy, p = 0.006). Homogeneity index (HI) values for PTV2 were closer to unity using IMRT (p = 0.0003). Mean parotid doses were 25.6 {+-} 2.7 Gy for IMRT and 42.0 {+-} 8.8 Gy with 3DCRT (p = 0.002). The parotid V30 in all IMRT plans was <45%. The mandible V50, V55, and V60 were significantly lower for the IMRT plans. Maximum spinal cord and brain stem doses were similar for the 2 techniques. IMRT provided superior target volume dose homogeneity and sparing of organs at risk. The magnitude of reductions in dose to the salivary glands and mandible are likely to translate into reduced incidence of xerostomia and osteoradionecrosis for patients with OCC.

Ahmed, Merina [Department of Radiotherapy, Royal Marsden Hospital, Sutton (United Kingdom); Hansen, Vibeke N. [Department of Physics, Royal Marsden Hospital, Sutton (United Kingdom); Harrington, Kevin J. [Department of Radiotherapy, Royal Marsden Hospital, Sutton (United Kingdom); Institute of Cancer Research, London (United Kingdom); Nutting, Christopher M. [Department of Radiotherapy, Royal Marsden Hospital, Sutton (United Kingdom)], E-mail:



Thiolated polycarbophil/glutathione: defining its potential as a permeation enhancer for oral drug administration in comparison to sodium caprate.  


Thiolated polyacrylates were shown to be permeation enhancers with notable potential. The aim of this study was to evaluate the permeation enhancing properties of a thiolated polycarbophil/glutathione (PCP-Cys/GSH) system for oral drug application in comparison to a well-established permeation enhancer, namely sodium caprate. In vitro permeation studies were conducted in Ussing-type chambers with sodium fluoresceine (NaFlu) and fluoresceine isothiocyanate labeled dextran (molecular mass 4?kDa; FD4) as model compounds. Bioavailability studies were carried out in Sprague Dawley rats with various formulations. Moreover, cytotoxic effects of both permeation enhancers were compared. Permeation enhancement ratios of 1% sodium caprate were found to be 3.0 (FD4) and 2.3 (NaFlu), whereas 1% PCP-Cys/0.5% GSH displayed enhancement ratios of 2.4 and 2.2. Both excipients performed at a similar level in vivo. Sodium caprate solutions increased oral bioavailability 2.2-fold (FD4) and 2.3-fold (NaFlu), while PCP-Cys hydrogels led to a 3.2-fold and 2.2-fold enhancement. Cell viability experiments revealed a significantly higher tolerance of Caco-2 cells towards 0.5% PCP-Cys (81% survival) compared to 0.5% sodium caprate (5%). As PCP-Cys is not absorbed from mucosal membranes due to its comparatively high molecular mass, systemic side-effects can be excluded. In conclusion, both systems displayed a similar potency for permeation enhancement of hydrophilic compounds. However, PCP-Cys seems to be less harmful to cultured cells. PMID:21554106

Perera, Glen; Barthelmes, Jan; Vetter, Anja; Krieg, Christof; Uhlschmied, Cindy; Bonn, Günther K; Bernkop-Schnürch, Andreas



Malignant mesothelioma  

PubMed Central

Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10–20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis.

Moore, Alastair J; Parker, Robert J; Wiggins, John



Has oral fluid the potential to replace serum for the evaluation of population immunity levels? A study of measles, rubella and hepatitis B in rural Ethiopia.  

PubMed Central

OBJECTIVE: To assess the suitability of using oral-fluid samples for determining the prevalence of immunity to vaccine-preventable infections. METHODS: Paired blood and oral-fluid samples were obtained from 853 individuals of all ages from a rural Ethiopian community. Oral fluid around the gums was screened for measles- and rubella-specific antibodies using enhanced IgG antibody capture (GAC) enzyme-linked immunosorbent assays (ELISAs), and for anti-HBc antibodies using a prototype GACELISA. IgG antibodies in serum to measles, rubella and HBc were determined using commercial ELISAs. FINDINGS: Relative to serum, oral fluid assay sensitivity and specificity were as follows: 98% and 87% for measles, 79% and 90% for rubella, and 43% and 87% for anti-HBc. These assay characteristics yielded population prevalence estimates from oral fluid with a precision equal to that of serum for measles (all ages) and rubella (ages < 20 years). CONCLUSION: Our results suggest that oral fluid could have the potential to replace serum in IgG antibody prevalence surveys. Further progress requires assessment of variation in assay performance between populations as well as the availability of standardized, easy to use assays.

Nokes, D. J.; Enquselassie, F.; Nigatu, W.; Vyse, A. J.; Cohen, B. J.; Brown, D. W.; Cutts, F. T.



Assessment of oral toxicity and safety of pentamethylchromanol (PMCol), a potential chemopreventative agent, in rats and dogs.  


2,2,5,7,8-Pentamethyl-6-chromanol (PMCol) was administered by gavage in rats for 28 days at dose levels of 0, 100, 500, and 2000mg/kg/day. PMCol administration induced decreases in body weight gains and food consumption, hepatotoxicity (increased TBILI, ALB, ALT, TP; increased relative liver weights; increased T4 and TSH), nephrotoxicity (increased BUN and BUN/CREAT, histopathology lesions), effect on lipid metabolism (increased CHOL), anemia, increase in WBC counts (total and differential), coagulation (FBGN upward arrow and PT downward arrow) and hyperkeratosis of the nonglandular stomach in the 2000mg/kg/day dose group (in one or both sexes). In the 500mg/kg/day dose group, toxicity was seen to a lesser extent. In the 100mg/kg/day dose group, only increased CHOL (females) was observed. To assess the toxicity of PMCol in male dogs it was administered orally by capsule administration for 28 days at dose levels of 0, 50, 200 and 800mg/kg/day (four male dogs/dose group). PMCol treatment at 800mg/kg/day resulted in pronounced toxicity to the male dogs. Target organs of toxicity were liver and thymus. Treatment at 200mg/kg/day resulted in toxicity consistent with slight adverse effect on the liver only. The results of the safety pharmacology study indicate that doses of 0, 50, 200 and 800mg/kg administered orally did not have an effect on the QT interval, blood pressures and body temperatures following dosing over a 24-h recording period. Under the conditions of this study, the no-observed-adverse effect level (NOAEL) for daily oral administration of PMCol by gavage for 28 days to male rats was 100mg/kg/day and 50mg/kg in male dogs. In female rats, the NOAEL was not established due to statistically significant and biologically meaningful increases in CHOL level seen in the 100mg/kg/day dose group. The results of these studies indicated that administration of PMCol at higher dose levels resulted in severe toxicity in dogs and moderate toxicity in rats, however, administration at lower levels is considered to be less likely to result in toxicity following 28 days of exposure. Sex-related differences were seen in rats. Male rats appeared to have greater sensitivity to nephrotoxicity, while female animals had a greater incidence of hepatoxicity and changes in hematological parameters evaluated, especially at a dose of 500mg/kg/day, which correlated to the higher plasma drug levels in female rats. It appeared that dogs were generally more sensitive than rats to oral administration of PMCol. Further examination of the potential toxic effects of PMCol in longer term studies is required prior to understanding the full risks of PMCol administration as a chemopreventative agent. PMID:20430063

Lindeblad, Matthew; Kapetanovic, Izet M; Kabirov, Kasim K; Detrisac, Carol J; Dinger, Nancy; Mankovskaya, Irina; Zakharov, Alexander; Lyubimov, Alexander V



Hematologic malignancies  

SciTech Connect

The principle aim of this book is to give practical guidelines to the modern treatment of the six important hematologic malignancies. Topics considered include the treatment of the chronic leukemias; acute leukemia in adults; the myeloproliferative disorders: polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis/agnogenic myeloid metaplasia; Hodgkin's Disease; non-Hodgkin's lymphoma; and Multiple Myeloma.

Hoogstraten, B.



The potential impact of the tension of the pelvic muscles on set-up errors in radiotherapy for pelvic malignancies.  


The purpose of the study reported here was to evaluate the potential impact of the tension of pelvic muscles on set-up errors. Twenty-nine consecutive patients with rectal cancer were included. The treatment simulation of the lateral beam in prone position was performed twice-with relaxed and next with maximally tense pelvic muscles. During the second simulation, the couch was moved so as to align the centre of the beam with the actual position of the skin mark tattooed during the first simulation. The bony landmarks on both images of corresponding lateral fields were matched. The beam's centre displacement and the rotation were measured using the beam image taken in relaxed position as a reference. The absolute values were used in calculation of the mean. For the anterior-posterior direction, the mean value of displacements was 15.3 mm, standard deviation (SD) 6.9 mm and the maximal value 37 mm. For the cranial-caudal direction, the mean value was 4.4 mm, SD 4 mm and the maximal value 17 mm. The mean rotation of the pelvis was 5.3 degrees, SD 2.4 degrees and maximal rotation 11 degrees. The majority of displacements were in the posterior (86%) and caudal (55%) directions. The majority of rotations were clockwise (76%). It was shown that pelvic muscle tension was the reason for anal verge displacements and mispositionings of the shielding block. This results in set-up inaccuracy, especially in the anterior-posterior direction, shielding block mispositioning and anal verge displacement. PMID:15764219

Bujko, Krzysztof; Czuchraniuk, Piotr; Zólciak, Agnieszka; Kukolowicz, Pawel; Kepka, Lucyna; Bielik, Agnieszka



Scedosporium apiospermum Soft Tissue Infection Successfully Treated with Voriconazole: Potential Pitfalls in the Transition from Intravenous to Oral Therapy  

Microsoft Academic Search

An immunocompromised patient with an invasive soft tissue infection due to Scedosporium apiospermum was successfully treated with voriconazole and surgical debridement. After transition from intravenous to oral therapy, successive adjustments of the oral dose were required to achieve complete resolution. For soft tissue infections due to molds characterized by thin, septate hyphae branching at acute angles, voriconazole should be considered

Joanna M. Schaenman; Daniel B. DiGiulio; Laurence F. Mirels; Nancy M. McClenny; Gerald J. Berry; Annette W. Fothergill; Michael G. Rinaldi; Jose G. Montoya



The potential of topoisomerase I inhibitors in the treatment of CNS malignancies: report of a synergistic effect between topotecan and radiation  

Microsoft Academic Search

Despite innovations in imaging, surgery, and radiation therapy, local failure remains the principle clinical problem in most CNS malignancies. To date, chemotherapy has not made a major impact in the treatment of most adult CNS tumors. The inroads made by chemotherapy in pediatric CNS malignancies suggest that novel drugs, or drug combinations, may improve therapy. Topoisomerase I (Topo I) inhibitors

John P. Lamond; Minesh P. Mehta; David A. Boothman



Myofibroblastic malignancies.  


Malignant tumors composed of myofibroblasts are increasingly being recognized, but their existence remains controversial. Currently accepted examples within this category represent spindle cell or pleomorphic neoplasms of the soft tissues with a spectrum of histological grades. Low- and intermediate-grade myofibrosarcomas are fascicular spindle cell neoplasms resembling fibrosarcoma or leiomyosarcoma. They infiltrate deep soft tissue with disproportionate involvement of head and neck sites and can recur locally but infrequently metastasize. They variably express myoid immunohistochemical markers, and their differential diagnosis includes benign myofibroblastic proliferations such as fasciitis and fibromatosis as well as other types of spindle cell sarcoma. High-grade (pleomorphic) myofibrosarcomas are an ultrastructurally defined subset of malignant fibrous histiocytoma, which they resemble in morphology and behavior. Inflammatory myofibroblastic tumor and infantile fibrosarcoma are neoplasms that have myofibroblastic features and have been included in this category, but they have distinctive genetic findings. This article reviews the concept of myofibrosarcoma and describes its variants. PMID:15220822

Fisher, Cyril



Use of a microprocessor in the control of malignant hypertension with sodium nitroprusside.  


In a malignant hypertensive, steady control of blood pressure at a pre-determined level has been achieved with the continuous intravenous infusion of sodium nitroprusside. A microprocessor was programmed to assess the patient's blood pressure and adjust the rate of nitroprusside infusion so that a mean pressure of 106 mmHg was achieved. Brief interruption of the nitroprusside infusion allowed the effectiveness of changes in oral therapy to be evaluated. Thiocyanate concentrations were measured throughout as an index of potential nitroprusside toxicity. After six days, blood pressure control was maintained with oral therapy alone and papilloedema had almost resolved. PMID:270994

Jackson, R V; Love, J B; Parkin, W G; Wahlqvist, M L; Williams, N S



Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review  

PubMed Central

Oral cancer is one of the major global threats to public health. The development of oral cancer is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are possible to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will yield important advances for detecting high-risk patients, monitoring preventive interventions, and assessing cancer risk and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from studies using appropriate animal carcinogenesis models. New approaches, such as molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy.

Tanaka, Takuji; Tanaka, Mayu; Tanaka, Takahiro



Oral epithelial dysplasia and squamous cell carcinoma following allogeneic hematopoietic stem cell transplantation: clinical presentation and treatment outcomes  

PubMed Central

Background Late complications of allogeneic hematopoietic stem cell transplantation (HSCT) include a risk of secondary malignancies, including oral cancers. Optimization of best clinical practices for early diagnosis and treatment of oral premalignant or malignant lesions requires an assessment of potential predisposing risk factors as well as treatment outcomes. Methods The medical records of patients who developed oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) following allogeneic HSCT were reviewed. Data on demographics, HSCT course, chronic graft-versus-host disease (cGVHD), smoking and alcohol consumption, oral lesion characteristics, mode of therapy and clinical outcome were recorded; landmark survival was calculated. Results Twenty-six patients with OED (n = 8) and OSCC (n = 18) were identified with a median follow-up of 26.5 and 21.5 months, respectively. Premalignant and malignant oral lesions were diagnosed at a median time of 2.5 and 8 years after HSCT, respectively. Chronic GVHD was present in 96% of patients and of these, 96% had oral involvement. Multifocal oral cancer was found in 28% of cases, and localized recurrence was observed in 44% of cases. Five-year overall survival was 75% and 70% for OED and OSCC, respectively. Conclusions These results suggest that oral cGVHD may be considered a potential risk factor for the development of OSCC following allogeneic HSCT. The observation that oral cancers were frequently multifocal and recurred locally supports the concept of field cancerization and suggests that these cancers may be more aggressive compared with the non-HSCT population. Vigilant follow-up and coordination of care between hematologists and oral health specialists are critical to minimize morbidity and mortality.

Mawardi, Hani; Elad, Sharon; Correa, M. Elvira; Stevenson, Kristen; Woo, Sook-Bin; Almazrooa, Soulafa; Haddad, Robert; Antin, Joseph H.; Soiffer, Robert; Treister, Nathaniel



Elevated microsatellite alterations at selected tetra-nucleotide (EMAST) in non-small cell lung cancers--a potential determinant of susceptibility to multiple malignancies.  


The present study evaluated the potential clinicopathologic significance of elevated microsatellite alteration at selected tetra-nucleotide (EMAST) in non-small cell lung cancer (NSCLC). Sixty-five NSCLCs (19 squamous cell carcinomas, 39 adenocarcinomas, one adenosquamous cell carcinoma, and 6 large cell carcinomas) were examined for EMAST in the ten selected tetra-nucleotide markers. Traditional microsatellite instability (MSI) in the five mono- or di-nucleotide markers of the Bethesda panel was also examined, and compared with EMAST. The incidence of EMAST was higher than that of traditional MSI, as 64.6% (42/65) and 12.3% (8/65) tumors respectively exhibited EMAST and traditional MSI in at least one marker. EMAST and traditional MSI appear to occur independently, as no significant association in their incidence was found (Fisher's exact test, P = 0.146). Subjects who exhibited EMAST in two or more markers had a significantly higher incidence of history of other malignant neoplasms (42.9% [9/21]), compared to those with less than two markers (16.3% [7/43] (Chi-square test, P = 0.021)). Taken together, impairment of molecular machinery for maintaining stable replication of the tetra-nucleotide-repeating regions, which would differ from machinery for mono- or di-nucleotide-repeating regions, may elevate susceptibility to NSCLCs and certain neoplastic diseases. Elucidation of the potential molecular mechanism of EMAST is expected to lead to a discovery of a novel genetic background determining susceptibility to NSCLC and other multiple neoplasms. This is the first report describing a clinicopathologic significance of EMAST in NSCLC. PMID:23412080

Arai, Hiromasa; Okudela, Koji; Oshiro, Hisashi; Komitsu, Noriko; Mitsui, Hideaki; Nishii, Teppei; Tsuboi, Masahiro; Nozawa, Akinori; Noishiki, Yasuharu; Ohashi, Kenichi; Inui, Kenji; Masuda, Munetaka



Salivary changes and dental caries as potential oral markers of autoimmune salivary gland dysfunction in primary Sjögren's syndrome  

Microsoft Academic Search

BACKGROUND: the classification criteria for primary Sjögren's syndrome (pSS) include a number of oral components. In this study we evaluated if salivary flow and composition as well as dental caries are oral markers of disease severity in pSS. METHODS: in 20 patients fulfilling the American-European Consensus criteria for pSS and 20 age-matched healthy controls whole and parotid saliva flow rates

Anne Marie Lynge Pedersen; Allan Bardow; Birgitte Nauntofte



Effects of feeding Spodoptera littoralis on lima bean leaves. I. Membrane potentials, intracellular calcium variations, oral secretions, and regurgitate components.  


Membrane potentials (V(m)) and intracellular calcium variations were studied in Lima bean (Phaseolus lunatus) leaves when the Mediterranean climbing cutworm (Spodoptera littoralis) was attacking the plants. In addition to the effect of the feeding insect the impact of several N-acyl Glns (volicitin, N-palmitoyl-Gln, N-linolenoyl-Gln) from the larval oral secretion was studied. The results showed that the early events upon herbivore attack were: a) a strong V(m) depolarization at the bite zone and an isotropic wave of V(m) depolarization spreading throughout the entire attacked leaf; b) a V(m) depolarization observed for the regurgitant but not with volicitin [N-(17-hydroxy-linolenoyl)-Gln] alone; c) an enhanced influx of Ca(2+) at the very edge of the bite, which is halved, if the Ca(2+) channel blocker Verapamil is used. Furthermore, the dose-dependence effects of N-acyl Gln conjugates-triggered influx of Ca(2+) studied in transgenic aequorin-expressing soybean (Glycine max) cells, showed: a) a concentration-dependent influx of Ca(2+); b) a configuration-independent effect concerning the stereochemistry of the amino acid moiety; c) a slightly reduced influx of Ca(2+) after modification of the fatty acid backbone by functionalization with oxygen and; d) a comparable effect with the detergent SDS. Finally, the herbivore wounding causes a response in the plant cells that cannot be mimicked by mechanical wounding. The involvement of Ca(2+) in signaling after herbivore wounding is discussed. PMID:15051862

Maffei, Massimo; Bossi, Simone; Spiteller, Dieter; Mithöfer, Axel; Boland, Wilhelm



Malignant melanoma.  


"Melanoma has become a major public health problem worldwide and its incidence in individuals of European origin continues to rise. Melanoma is the third most common cancer in Australia (in men and women); the fifth in the United States (in men and women); and the 12th in men and the sixth in women in the United Kingdom" (J. G. Thompson, R. A. Scolyer, & R. F. Kefford, 2009, p. 362). The American Cancer Society estimated that about 68,720 new melanomas were diagnosed in the United States during 2009, resulting in about 8,650 deaths. The purpose of this article is to explain the pathophysiologic components of malignant melanoma. PMID:21876415

Wilkerson, Brenda L


Epidemiology of Smoking-Related Malignancies  

PubMed Central

It is well known that tobacco use is the major single cause of cancer mortality. Cigarette smokers have increased risk for cancer of the lung, bladder, oral cavity and pharynx, pancreas, kidney, larynx, and esophagus. Although smoking is the primary risk factor for several of the malignancies, each tumour site has other known or suspected risk factors. The author describes the smoking association for each tumour site and reviews other risk factors for these smoking-related malignancies.

Spinelli, John J.



[Malignant melanoma].  


Malignant melanomas have one of the highest increases in incidence among malignancies. There are four histological types: superficial spreading melanoma, nodular melanoma, acrolentiginous melanoma and lentigo maligna melanoma. The TNM classification considers depth of infiltration (Clark's level), vertical tumor thickness (Breslow's thickness), ulceration of the primary tumor, satellites and in-transit metastases as well as regional lymph node and distant metastases. An adequate margin of clearance is important in primary resection. Sentinel lymph node biopsy is relevant in all melanomas with a Breslow tumor thickness >1 mm without clinically suspicious lymph nodes. In the case of lymph node metastases therapeutic dissection is recommended, in patients with in-transit metastases of the extremities hyperthermic isolated limb perfusion with cytostatic agents may be indicated. Resection of distant metastases can be useful if only one site is affected or a R0 resection is expected to be achieved. Adjuvant, neoadjuvant and palliative procedures, such as radiotherapy, chemotherapy and immunotherapy are additional treatment options. PMID:19444395

Göhl, J; Hohenberger, W; Merkel, S



Malignant hyperthermia  

PubMed Central

Malignant hyperthermia (MH) is an uncommon, life-threatening pharmacogenetic disorder of the skeletal muscle. It presents as a hypermetabolic response in susceptible individuals to potent volatile anesthetics with/without depolarizing muscle relaxants; in rare cases, to stress from exertion or heat stress. Susceptibility to malignant hyperthermia (MHS) is inherited as an autosomally dominant trait with variable expression and incomplete penetrance. It is known that the pathophysiology of MH is related to an uncontrolled rise of myoplasmic calcium, which activates biochemical processes resulting in hypermetabolism of the skeletal muscle. In most cases, defects in the ryanodine receptor are responsible for the functional changes of calcium regulation in MH, and more than 300 mutations have been identified in the RYR1 gene, located on chromosome 19q13.1. The classic signs of MH include increase of end-tidal carbon dioxide, tachycardia, skeletal muscle rigidity, tachycardia, hyperthermia and acidosis. Up to now, muscle contracture test is regarded as the gold standard for the diagnosis of MHS though molecular genetic test is used, on a limited basis so far to diagnose MHS. The mortality of MH is dramatically decreased from 70-80% to less than 5%, due to an introduction of dantrolene sodium for treatment of MH, early detection of MH episode using capnography, and the introduction of diagnostic testing for MHS. This review summarizes the clinically essential and important knowledge of MH, and presents new developments in the field.



Identification of pregnancy-associated plasma protein A as a migration-promoting gene in malignant pleural mesothelioma cells: a potential therapeutic target  

PubMed Central

Despite recent advances in treatment, malignant pleural mesothelioma (MPM) remains a deadly disease. Targeted therapy generated broad interests and is highly expected for the treatment of MPM, yet promising preclinical results have not been translated into substantial clinical benefits for the patients. In this study, we tried to identify the genes which play functional roles in cell migration as well as to test whether they can be used as novel targets for molecular targeted therapy for MPM in preclinical model. In our study, pregnancy-associated plasma protein A (PAPPA) was identified as a gene whose expression level is correlated with MPM cell migration by correlation analysis combining MPM cell migration ability and their gene expression profiles. Highly migratory cells were selected from MPM cell lines, MSTO-211H, NCI-H290 and EHMES-1 in vitro and up-regulation of PAPPA in these cells were confirmed. In vitro, PAPPA was demonstrated to stimulate the MPM cell migration via cleavage of insulin-like growth factor-binding protein-4 and subsequent release of IGF-1. Gene silencing of PAPPA in MPM cells led to reduced migration, invasion and proliferation. Furthermore, PAPPA shRNA transfected NCI-H290 when orthotopically inoculated into pleural cavity of severe combined immunodeficiency recipient mice, failed to develop tumors and produce bloody pleural effusion as control shRNA transfected cells did. Our study suggests that PAPPA plays a functional role in promoting MPM cell migration and it might serve as a potential therapeutic target for the treatment of MPM.

Huang, Jun; Tabata, Sho; Kakiuchi, Soji; The Van, Trung; Goto, Hisatsugu; Hanibuchi, Masaki; Nishioka, Yasuhiko



Green tea: a promising natural product in oral health.  


Green tea is a leading beverage in the Far East for thousands of years; it is regarded for a long time as a health product. Green tea is important source of polyphenol antioxidants. Polyphenols including epigallocatechin 3 gallate (EGCG) constitute the most interesting components in green tea leaves. Green tea has the potential to protect against various malignant, cardiovascular and metabolic diseases. There is a growing body of evidence pointing a beneficial role of green tea and its polyphenols in oral health. Green tea protects against bacterial induced dental caries. Tea polyphenols possess antiviral properties, believed to help in protection from influenza virus. Additionally, green tea polyphenols can abolish halitosis through modification of odorant sulphur components. Oral cavity oxidative stress and inflammation, consequent to cigarette smoking and cigarettes' deleterious compounds nicotine and acrolein, may be reduced in the presence of green tea polyphenols. Generally, green tea defends healthy cells from malignant transformation and locally has the ability to induce apoptosis in oral cancer cells. All together, there is an increasing interest in the health benefits of green tea in the field of oral health. Nonetheless, there is still a need for more clinical and biological studies to support guidelines for green tea intake as part of prevention and treatment of specific oral pathologies. PMID:22226360

Narotzki, Baruch; Reznick, Abraham Z; Aizenbud, Dror; Levy, Yishai



Transgenic Mice Expressing Constitutively Active Akt in Oral Epithelium Validate Klf4 as a Potential Biomarker of Head and Neck Squamous Cell Carcinoma  

PubMed Central

Background Head and neck squamous cell carcinoma (HNSCC) is a common human neoplasia, of poor prognosis and survival, which frequently displays Akt overactivation. Previously, we reported that mice expressing high levels of constitutively Akt activity (myrAkt) in oral epithelia develop lesions and tumors in the oral cavity. Materials and Methods Functional genomics of primary keratinocytes from different transgenic mouse lines and immunostaining of mouse and human samples were performed in order to identify and validate putative biomarkers of oral cancer progression. Results The expression of KLF4 was found to be increased only in tumor prone samples from mice bearing overactivation of Akt. Such increased expression was confirmed in oral dysplasias and tumors arising in those mice. Tissue microarray analysis of human samples confirmed the association between active Akt and increased KLF4 expression. Conclusion These data support the notion that KLF4 is potentially a reliable marker of HNSCC, and that myrAkt transgenic mice are valuable tools for preclinical research of HNSCC.

Moral, Marta; Segrelles, Carmen; Martinez-Cruz, Ana Belen; Lorz, Corina; Santos, Mirentxu; Garcia-Escudero, Ramon; Lu, Jerry; Buitrago, Agueda; Costa, Clotilde; Saiz, Cristina; Ariza, Jose M.; Duenas, Marta; Rodriguez-Peralto, Jose L; Martinez-Tello, Francisco J; Rodriguez-Pinilla, Maria; Sanchez-Cespedes, Montserrat; DiGiovanni, John; Paramio, Jesus M.



The Problem of Atypical Neuroleptic Malignant Syndrome  

PubMed Central

Neuroleptic malignant syndrome is a serious and potentially fatal adverse effect of antipsychotic medications. Although diagnostic criteria for neuroleptic malignant syndrome have been established and are widely accepted and used, it should be recognized that atypical presentations occur, particularly during treatment with atypical antipsychotics. However, it remains unclear whether these atypical presentations represent early or impending neuroleptic malignant syndrome. Furthermore, since neuroleptic malignant syndrome is a diagnosis of exclusion, careful consideration of other neuropsychiatric conditions should occur. Relying on creatine phosphokinase elevation may result in an incorrect diagnosis of atypical neuroleptic malignant syndrome. We wish to present a case of this diagnostic dilemma in a patient with catatonia.

Surber, Susan A.



Peptides in oral diseases.  


The oral cavity is home to numerous viruses and micro-organisms recognized as having a role in various oral diseases as well as in infections in other parts of the body. Indeed, in general a microbial infection underlies or is believed to underlie the ample spectrum of oral diseases, from tooth enamel decay to periodontal lesions, from candidiasis to virus-induced oral squamous cell carcinomas, and bullous autoimmune oral disorders. This clinico-pathological context stresses the need of targeted therapies to specifically kill infectious agents in a complex environment such as the oral cavity, and explains the current interest in exploring peptide-based therapeutic approaches in oral and dental research. Here, we review the therapeutic potential of antimicrobial peptides such as LL-37, beta defensins, adrenomedullin, histatins, and of various peptides modulating gene expression and immuno-biological interaction(s) in oral diseases. PMID:22236124

Lucchese, Alberta; Guida, Agostino; Petruzzi, Massimo; Capone, Giovanni; Laino, Luigi; Serpico, Rosario



Strategies of targeting oral drug delivery systems to the colon and their potential use for the treatment of colorectal cancer.  


Colorectal cancer (CRC) is the third most common cause of cancer-related death in both men and women. Often, surgical intervention remains the choice in treating CRC. Traditional dosage forms used for treating CRC deliver drug to wanted as well as unwanted sites of drug action resulting in several adverse side effects. Targeted oral drug delivery systems are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific delivery of a drug to colon increases its concentration at the target site, and thus requires a lower dose with reduced incidence of side effects. The major obstacle to be overcome for successful targeting of drug to colon through oral route is that drug absorption/degradation must be avoided in stomach and small intestine before the dosage form reaches colon. The review includes discussion of physiological factors that must be considered when targeting drugs directly to colorectal region, an outline on drugs used for treatment and prevention of CRC, and a brief description of various types of colon-targeted oral drug delivery systems. The focus is on the assessment of various formulation approaches being investigated for oral colon-specific delivery of drugs used in the treatment and prevention of CRC. PMID:22681390

Krishnaiah, Yellela S R; Khan, Mansoor A



Metabolism of [D10]Phenanthrene to Tetraols in Smokers for Potential Lung Cancer Susceptibility Assessment: Comparison of Oral and Inhalation Routes of Administration  

PubMed Central

Polycyclic aromatic hydrocarbons (PAHs) are believed to be among the causative agents for lung cancer in smokers. PAHs require metabolic activation for carcinogenicity. One pathway produces diol epoxides that react with DNA, causing mutations. Because diol epoxides are converted to tetraols, quantitation of tetraols can potentially be used to identify smokers who may be at higher risk for lung cancer. Our approach uses [D10]phenanthrene, a labeled version of phenanthrene, a noncarcinogenic PAH structurally analogous to carcinogenic PAH. Although smokers are exposed to PAH by inhalation, oral dosing would be more practical for phenotyping studies. Therefore, we investigated [D10]phenanthrene metabolism in smokers after administration by inhalation in cigarette smoke or orally. Sixteen smokers received 10 ?g of [D10]phenanthrene in a cigarette or orally. Plasma and urine samples were analyzed for [D10]r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene ([D10]PheT), the major end product of the diol epoxide pathway, by gas chromatography-negative ion chemical ionization-tandem mass spectrometry. The ratios of [D10]PheT (oral dosing/inhalation) in 15 smokers were 1.03 ± 0.32 and 1.02 ± 0.35, based on plasma area under the concentration-time curve (0-?) and total 48-h urinary excretion, respectively. Overall, there was no significant difference in the extent of [D10]PheT formation after the two different routes of exposure in smokers. A large interindividual variation in [D10]PheT formation was observed. These results demonstrate that the level of [D10]PheT in urine after oral dosing of [D10]phenanthrene can be used to assess individual capacity of PAH metabolism by the diol epoxide pathway.

Zhong, Yan; Wang, Jing; Carmella, Steven G.; Hochalter, J. Bradley; Rauch, Diane; Oliver, Andrew; Jensen, Joni; Hatsukami, Dorothy K.; Upadhyaya, Pramod; Zimmerman, Cheryl



Potential use of chitosan nanoparticles for oral delivery of DNA vaccine in Asian sea bass (Lates calcarifer) to protect from Vibrio (Listonella) anguillarum.  


In recent years, attention has been focused on the possibility of utilizing DNA vaccines in fish aquaculture. A successful regime for intramuscular injection of naked DNA into fish has been developed and novel methods to deliver this DNA to fish are under investigation. The potential of chitosan as a polycationic gene carrier for oral administration has been explored since 1990s. The present study examines the potential efficacy of DNA vaccine against Vibrio anguillarum through oral route using chitosan nanoparticles encapsulation. The porin gene of V. anguillarum was used to construct DNA vaccine using pcDNA 3.1, a eukaryotic expression vector and the construct was named as pVAOMP38. The chitosan nanoparticles were used to deliver the constructed plasmid. In vitro and in vivo expression of porin gene was observed in sea bass kidney cell line (SISK) and in fish, respectively by fluorescent microscopy. The cytotoxicity of chitosan encapsulated DNA vaccine construct was analyzed by MTT assay and it was found that the cytotoxicity of pVAOMP38/chitosan was quite low. Distribution of gene in different tissues was studied in fish fed with the DNA (pVAOMP38) encapsulated in chitosan by using immunohistochemistry. The results indicate that DNA vaccine can be easily delivered into fish by feeding with chitosan nanoparticles. After oral vaccination Asian sea bass were challenged with Vibrio anguillarum by intramuscular injection. A relative percent survival (RPS) rate of 46% was recorded. The results indicate that Sea bass (Lates calcarifer) orally vaccinated with chitosan-DNA (pVAOMP38) complex showed moderate protection against experimental V. anguillarum infection. PMID:18479939

Rajesh Kumar, S; Ishaq Ahmed, V P; Parameswaran, V; Sudhakaran, R; Sarath Babu, V; Sahul Hameed, A S



Induction of liver preneoplastic foci in F344 rats subjected to 28-day oral administration of diheptyl phthalate and its in vivo genotoxic potential.  


To investigate possible potential inducing preneoplastic lesions in liver and in vivo genotoxic potential of diheptyl phthalate (DHP), male F344 rats were subjected to repeated oral administration of DHP at 0, 2.5 or 5 g/kg/day for 28 days. In addition, F344 rats were subjected to once or 14 repeated oral administrations of 5 g/kg/day of DHP, and their livers were subjected to analysis in an alkaline single-cell gel electrophoresis (comet) assay. Furthermore, based on the results of these studies, partial hepatectomized male F344 rats given once, three times, and 14 repeated oral administration of 0, 2.5 or 5 g/kg body weight of DHP were examined by an in vivo liver initiation assay. In a 28-day repeated dose toxicity study, the number and area of glutathione-S-transferase placental form (GST-P) positive foci, a marker of hepatocellular preneoplastic lesions in rats, were significantly increased in DHP-treated groups compared with controls. At 24h after the 14 repeated administrations of DHP, DNA migration, a marker of DNA damage in the comet assay, was significantly induced in DHP-treated rat livers, whereas single treatment did not show such an alteration. In an in vivo liver initiation assay, a significant increase in the number and area of GST-P positive foci was observed in DHP-treated groups subjected to 14 repeated oral administrations of DHP as compared with the control group. These results indicate that DHP may induce altered hepatocellular foci in liver of rats which suggests that DHP is a genotoxic carcinogen in the liver of rats. PMID:19643158

Jin, Meilan; Dewa, Yasuaki; Kawai, Masaomi; Nishimura, Jihei; Saegusa, Yukie; Kemmochi, Sayaka; Harada, Tomoaki; Shibutani, Makoto; Mitsumori, Kunitoshi



Chromosomal instability, aneuploidy and routine high-resolution DNA content analysis in oral cancer risk evaluation.  


Carcinogen exposure of the oral cavity is thought to create an extensive 'field cancerization'. According to this model, a very early precursor of oral cancer is a patch of normal-appearing mucosa in which stem cells share genetic/genomic aberrations. These precancerous fields then become clinically visible as white and red lesions (leuko- and erythro-plakias), which represent the vast majority of the oral potentially malignant disorders. This review focuses on aneuploidy (where it is from) and on biomarkers associated with DNA aneuploidy in oral mucosa and oral potentially malignant disorders, as detected by DNA image and flow cytometry. Data from the literature strongly support the association of DNA ploidy with dysplasia. However, work is still needed to prove the clinical value of DNA ploidy in large-scale prospective studies. Using high-resolution DNA flow cytometry with fresh/frozen material and the degree of DNA aneuploidy (DNA Index) might improve the prediction of risk of oral cancer development. PMID:23130927

Giaretti, Walter; Pentenero, Monica; Gandolfo, Sergio; Castagnola, Patrizio



limited potentiation of blood pressure in response to oral tyramine by the anti-Parkinson brain selective multifunctional monoamine oxidase-AB inhibitor, M30.  


One of the limitations of non-selective monoamine oxidase (MAO) inhibitors as anti-depressant or anti-Parkinson drugs is their ability to potentiate the cardiovascular effect of oral tyramine, resulting from inhibition of systemic MAO-A and release of noradrenaline. We have investigated the cardiovascular effect of oral tyramine in response to the novel multifunctional, brain selective MAO-AB inhibitor, M30 [5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline], and compared it to the classical non-selective inhibitor tranylcypromine (TCP) in rats. We also measured MAO-A and B in the striatum, hippocampus, liver, and small intestine and determined brain levels of dopamine, noradrenaline, and serotonin. At the doses employed, intraperitoneal (i.p.) M30 (5 and 10 mg/kg) selectively inhibited brain MAO-A and B by more than 85%, with little inhibition of liver and small intestine enzymes while raising striatal levels of dopamine, noradrenaline, and serotonin. In contrast to TCP (10 mg/kg, i.p.), which fully inhibits both enzymes in the brain and systemic organs and significantly potentiates the tyramine pressor effect, M30 had a limited pressor effect as compared to it and controls. The limited potentiation of tyramine pressor effect by M30, its ability to raise brain levels of aminergic neurotransmitters together with its neuroprotective and neurorestorative activities make this drug potentially important as an anti-depressant and anti-Parkinsonian agent, for which it is being developed. PMID:19894083

Gal, Shunit; Abassi, Zaid A; Youdim, Moussa B H



The application of vizilite in oral cancer.  


This article depicts the various applications of Vizilite plus in oral cancer. The oral cavity demonstrates a variety of red and white, pigmented and vesiculo- bullous lesions. Oral cancer still happens to carry the highest mortality worldwide, especially in India. In India, the prime focus is on the downstreaming of oral cancer from an advanced stage to an early diseased state. The techniques that are promoted to facilitate an earlier detection and diagnosis of an oral malignancy include Toluidine blue, ViziLite Plus with TBlue, ViziLite, Microlux DL, Orascoptic DK, VEL scope, Oral CDx and brush biopsy. PMID:23450083

Sambandham, Thirugnana; Masthan, K M K; Kumar, M Sathish; Jha, Abhinav



Potential role of oral anticoagulants in the treatment of patients with coronary artery disease: focus on dabigatran.  


The pharmacologic management of patients with high-risk coronary artery disease consists of aspirin and a P2Y12 receptor inhibitor. Chronic oral anticoagulation with warfarin is the major treatment strategy to attenuate thromboembolism or stroke in patients with deep vein thrombosis, pulmonary embolism, heart failure and atrial fibrillation. A substantial percentage of the latter group of patients have coronary artery disease and may require stenting with long-term dual antiplatelet therapy in addition to therapy with warfarin to reduce arterial ischemic events in addition to stroke. These new oral anticoagulants have been developed for long-term therapy to overcome the limitations of warfarin. Dabigatran is a direct thrombin inhibitor and its role in patients with acute coronary syndrome is being explored. PMID:23968500

Doraiswamy, Vijay A; Slepian, Marvin J; Gesheff, Martin G; Tantry, Udaya S; Gurbel, Paul A



EEG and blood level of the potential antidepressant paroxetine after a single oral dose to normal volunteers  

Microsoft Academic Search

The quantitative electroencephalogram (EEG) and plasma concentration of the antidepressant paroxetine were monitored in five normal volunteers after a single oral dose of 70 mg paroxetine and placebo. Peak plasma concentration occurred 4–6 h post-dose. Placebo had little effect on the EEG but the effects of paroxetine were statistically significant at 6 h post-dose. The EEG changes after treatment consisted

G. R. McClelland; P. Raptopoulos



Oral cancer screening approach based on labeling exfoliated oral cells with molecularly-targeted optical contrast agents  

NASA Astrophysics Data System (ADS)

Early detection is a potential key to improving the survival rates of oral cancer patients and reducing the morbidity associated with treatment. We seek to improve upon methods of detecting of early malignancies with oral brush biopsies by using immunofluorescence-based assessment of the expression of multiple well-described markers commonly overexpressed in oral cancers, such as Epidermal Growth Factor Receptor (EGFR) and Cytokeratin 8 (CK8). Furthermore, since abnormal cells are often scarce in brush biopsy samples, we seek to use magnetic microparticles targeted to these markers as a means of enriching the concentration of abnormal cells. Finally, we plan to conduct a small pilot study using these methods with brush biopsies from patients of the M. D. Anderson Cancer Center Head and Neck Clinic.

Leautaud, Veronica; Horres, Charles R.; Bhattar, Vijayashree S.; Williams, Michelle D.; Gillenwater, Ann M.; Richards-Kortum, Rebecca R.



Squamous cell carcinoma of the oral tissues: a comprehensive review for oral healthcare providers.  


North Americans in 2004 were projected to die from oral and pharyngeal cancer at a rate of 1.2 per hour. Oral healthcare providers can be instrumental in reducing the incidence of oral and pharyngeal premalignant and malignant lesions by identifying patients with high-risk behavior, educating their patients about the consequences of their high-risk behavior, and by early detection of premalignant and malignant conditions. The fact only 34% of the cancers of the oral cavity and larynx are localized at the time of diagnosis and evidence that at least one third of the patients diagnosed with an oral or pharyngeal malignancy have undergone oral cancer screening within the past three years suggests the current protocol for the early detection of pre-malignant or malignant changes appears to be deficient. To facilitate early diagnosis, oral healthcare providers must take into consideration the capriciousness of oral cancer and must be familiar with the availability and application of diagnostic modalities beyond conventional visual inspection and palpation of oral soft tissues. This article provides a comprehensive review of the disease for healthcare professionals. PMID:16299602

Bsoul, Samer A; Huber, Michaell A; Terezhalmy, Geza T



Induction of Parathyroid Hormone-related Peptide by the Ras Oncogene: Role of Ras Farnesylation Inhibitors as Potential Therapeutic Agents for Hypercalcemia of Malignancy1  

Microsoft Academic Search

Parathyroid hormone related peptide (PTHRP) is the major causal agent in the syndrome of malignancy-associated hypercalcemia (MAH). Several studies have shown that PTHRP production is increased in re sponse to growth factors and oncogenes, such as Tpr-Met, that are asso ciated with the tyrosine kinase signaling pathway. Using site-directed mutagenesis of Tpr-Met and chemical inhibitors of phosphotidylinositol-3 kinase and Ras

Fasika Aklilu; Morag Park; David Goltzman; Shafaat Ahmed Rabbani


Malignant hyperthermia  

PubMed Central

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered. Thanks to the dramatic progress in understanding the clinical manifestation and pathophysiology of the syndrome, the mortality from MH has dropped from over 80% thirty years ago to less than 5%.

Rosenberg, Henry; Davis, Mark; James, Danielle; Pollock, Neil; Stowell, Kathryn



Probiotics and oral health  

PubMed Central

Probiotics utilize the naturally occurring bacteria to confer health benefits. Traditionally, probiotics have been associated with gut health, and are being mainly utilized for prevention or treatment of gastrointestinal infections and disease; however, recently, several studies have suggested the use of probiotics for oral health purposes. The aim of this review is to understand the potential mechanism of action of probiotic bacteria in the oral cavity and summarize their observed effects with respect to oral health.

Rastogi, Pavitra; Saini, Himani; Dixit, Jaya; Singhal, Rameshwari



Oral mucositis.  


Mucositis and xerostomia are the most common oral complications of the non-surgical therapy of cancer. Mucositis, a common sequel of radio- (DXR), chemo-(CXR) and radiochemo-therapy in patients with cancer, or patients requiring haemopoietic stem cell transplants (HSCT), has a direct and significant impact on the quality of life and cost of care, and also affects survival--because of the risk of infection. Apart from dose reduction, preventive and treatment options for mucositis are scarce, although multiple agents have been tested. Evidence suggests that cryotherapy, topical benzydamine and amifostine might provide some benefit in specific situations. The recombinant human keratinocyte growth factor Palifermin (Kepivance) was recently approved as a mucositis intervention in patients receiving conditioning regimens before HSCT for the treatment of haematological malignancies. A number of mechanistically based interventions are in various stages of development. Unfortunately, many other approaches have not been rigorously tested. This paper reviews the clinical features, prevalence, diagnosis, complications, pathogenesis, prophylaxis and management of mucositis. PMID:16700732

Scully, C; Sonis, S; Diz, P D



Oral Candidiasis  


... . Oral Candidiasis Oropharyngeal / Esophageal Candidiasis ("Thrush") Candidiasis that develops in the mouth or ... other Fungal topics, visit the Fungal Homepage. Oral Candidiasis Topics Definition What is oral candidiasis? Symptoms Redness ...


Oral Leukoplakia as It Relates to HPV Infection: A Review  

PubMed Central

Leukoplakia is the most common potentially malignant lesion of the oral cavity and can be categorised according to its clinical appearance as homogeneous or nonhomogenous. Tobacco and areca nut use, either alone or in combination are the most common risk factors for oral leukoplakia, but some oral leukoplakias are idiopathic. Some leukoplakias arise within fields of precancerized oral epithelium in which the keratinocytes may be at different stages of cytogenetic transformation. Leukoplakias may unpredictably regress, may remain stable, or may progress to carcinoma. There is a greater risk of carcinomatous transformation of idiopathic leukoplakia, of non-homogenous leukoplakia, of leukoplakia affecting the floor of the mouth; the ventrolateral surface of the tongue and the maxillary retromolar and adjoining soft palate (collectively called high-risk sites), of leukoplakia with high-grade epithelial dysplasia, and of leukoplakia in which the keratinocytes carry cytogenetic alterations associated with carcinomatous transformation. Although there appears to be some link between human papillomavirus (HPV) and oral leukoplakia, there is little evidence to support a causal relationship either between HPV infection and oral leukoplakia or between HPV-infected leukoplakic keratinocytes and their carcinomatous transformation.

Feller, L.; Lemmer, J.



The protease inhibitor, Bowman-Birk Inhibitor, suppresses experimental autoimmune encephalomyelitis: a potential oral therapy for multiple sclerosis.  


Available treatments for multiple sclerosis (MS) require frequent injections and have significant side effects. Proteases generated during inflammation are involved in the induction of tissue damage during inflammatory demyelination in the central nervous system (CNS). The Bowman-Birk Inhibitor (BBI), a soy-derived protease inhibitor with anti-carcinogenic and anti-inflammatory properties, has been shown to be well tolerated in clinical trials for pre-cancerous conditions, such as oral leukoplakia and the inflammatory disease, ulcerative colitis. We hypothesized that BBI may modulate experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The BBI concentrate (BBIC), a soybean extract enriched in BBI, was administered to myelin basic protein (MBP)-immunized Lewis rats by gastric gavage in different treatment regimens, during the induction or the effector phase of disease. BBIC significantly delayed disease onset and suppressed disease severity, clinically and pathologically, in all treatment protocols. Both in vitro and ex vivo, BBIC inhibited MBP-specific proliferation of lymph node cells. BBIC reduced the activity of matrix metalloproteinase (MMP)-2 and -9 in spleen cell supernatants and was detected in the CNS of treated rats. BBIC suppresses EAE, it can be administered orally, and it is safe and relatively inexpensive. It may have a therapeutic role in patients with MS. PMID:17262995

Gran, B; Tabibzadeh, N; Martin, A; Ventura, E S; Ware, J H; Zhang, G X; Parr, J L; Kennedy, A R; Rostami, A M



BI-10773, a sodium-glucose cotransporter 2 inhibitor for the potential oral treatment of type 2 diabetes mellitus.  


BI-10773, being developed by Boehringer Ingelheim Corp, is a sodium-glucose cotransporter (SGLT)2 inhibitor for the oral treatment of type 2 diabetes mellitus (T2DM). Preclinical and clinical research has demonstrated that inhibition of SGLT2, the major pathway of renal glucose reabsorption, leads to increased urinary glucose excretion with concomitant reductions in fasting and postprandial plasma glucose levels, HbA1c levels and body mass. In phase I clinical trials in patients with T2DM, once-daily BI-10773 increased urinary glucose excretion resulting in dose-proportional reductions in fasting plasma glucose and mean daily glucose levels. BI-10773 was not associated with significant hypoglycemic episodes or other clinically important adverse events. Because of its mechanism of action, BI-10773 may be combined with other oral antidiabetic agents; indeed, the results of small trials suggested that coadministration of BI-10773 and metformin was safe and well tolerated. In animal studies, BI-10773 correlated with an increase in urinary volume and a reduction in body fat but not water content. This may represent an additional benefit of BI-10773 for the control of T2DM. At the time of publication, phase III clinical trials of BI-10773 were underway. PMID:20872321

Aires, Inês; Calado, Joaquim



In vivo Raman spectroscopic identification of premalignant lesions in oral buccal mucosa  

NASA Astrophysics Data System (ADS)

Cancers of oral cavities are one of the most common malignancies in India and other south-Asian countries. Tobacco habits are the main etiological factors for oral cancer. Identification of premalignant lesions is required for improving survival rates related to oral cancer. Optical spectroscopy methods are projected as alternative/adjunct for cancer diagnosis. Earlier studies have demonstrated the feasibility of classifying normal, premalignant, and malignant oral ex-vivo tissues. We intend to evaluate potentials of Raman spectroscopy in detecting premalignant conditions. Spectra were recorded from premalignant patches, contralateral normal (opposite to tumor site), and cancerous sites of subjects with oral cancers and also from age-matched healthy subjects with and without tobacco habits. A total of 861 spectra from 104 subjects were recorded using a fiber-optic probe-coupled HE-785 Raman spectrometer. Spectral differences in the 1200- to 1800-cm-1 region were subjected to unsupervised principal component analysis and supervised linear discriminant analysis followed by validation with leave-one-out and an independent test data set. Results suggest that premalignant conditions can be objectively discriminated with both normal and cancerous sites as well as from healthy controls with and without tobacco habits. Findings of the study further support efficacy of Raman spectroscopic approaches in oral-cancer applications.

Singh, S. P.; Deshmukh, Atul; Chaturvedi, Pankaj; Murali Krishna, C.



The relevance of uniform reporting in oral leukoplakia: Definition, certainty factor and staging based on experience with 275 patients  

PubMed Central

The aim of the present study was to evaluate the definition of oral leukoplakia, proposed by the WHO in 2005 and taking into account a previously reported classification and staging system, including the use of a Certainty factor of four levels with which the diagnosis of leukoplakia can be established. In the period 1997-2012 a hospital-based population of 275 consecutive patients with a provisional diagnosis of oral leukoplakia has been examined. In only 176 patients of these 275 patients a firm diagnosis of leukoplakia has been established based on strict clinicopathological criteria. The 176 patients have subsequently been staged using a classification and staging system based on size and histopathologic features. For use in epidemiological studies it seems acceptable to accept a diagnosis of leukoplakia based on a single oral examination (Certainty level 1). For studies on management and malignant transformation rate the recommendation is made to include the requirement of histopathologic examination of an incisional or excisional biopsy, representing Certainty level 3 and 4, respectively. This recommendation results in the following definition of oral leukoplakia: “A predominantly white lesion or plaque of questionable behaviour having excluded, clinically and histopathologically, any other definable white disease or disorder”. Furthermore, we recommend the use of strict diagnostic criteria for predominantly white lesions for which a causative factor has been identified, e.g. smokers’ lesion, frictional lesion and dental restoration associated lesion. Key words:Oral epithelial dysplasia, oral leukoplakia, potentially malignant oral disorders.

Brouns, Elisabeth R E A.; Baart, Jacques A.; Bloemena, Elisabeth; Karagozoglu, Hakki



Immunohistochemical analysis of syndecan-1 in leukoplakia and oral submucous fibrosis  

PubMed Central

Background: Syndecan-1 is abundant in normal tissues and reduced in squamous cell carcinomas. Leukoplakia and oral submucous fibrosis (OSF) are oral pre-cancerous disorders that have potential for malignant transformation. The aim of this study was to evaluate the expression of syndecan-1 in leukoplakia and OSF and to identify its role as a reliable marker for predicting malignant changes. Materials and Methods: Expression of syndecan-1 was examined immunohistochemically in 42 cases of oral leukoplakia with or without epithelial dysplasia, 28 cases of OSF and 10 cases of normal oral epithelia as control. Mann-Whiteny ‘U’ test was used for statistical analysis and the level of significance was fixed at P < 0.05. Results: Intense syndecan-1 expression was observed in nine cases with normal epithelium. Immunopositivity was lost gradually as the extent of epithelial dysplasia increased. The significant reduction in syndecan-1 expression was observed in leukoplakia as epithelial dysplasia progressed from moderate or severe. Similarly, significant reduction was observed in staining intensities in OSF with dysplasia. Conclusion: The results reveal that down-regulation of syndecan-1 expression is associated with dysplastic changes in leukoplakia and OSF. Thus syndecan-1 can be considered as marker for predicting malignant changes.

Kamat, Sushant S.; Kumar, G. S.; Koshy, Ajit V.



Transplantation-associated long-term immunosuppression promotes oral colonization by potentially opportunistic pathogens without impacting other members of the salivary bacteriome.  


Solid-organ transplant recipients rely on pharmacological immunosuppression to prevent allograft rejection. The effect of such chronic immunosuppression on the microflora at mucosal surfaces is not known. We evaluated the salivary bacterial microbiome of 20 transplant recipients and 19 nonimmunosuppressed controls via 454 pyrosequencing of 16S rRNA gene amplicons. Alpha-diversity and global community structure did not differ between transplant and control subjects. However, principal coordinate analysis showed differences in community membership. Taxa more prevalent in transplant subjects included operational taxonomic units (OTUs) of potentially opportunistic Gammaproteobacteria such as Klebsiella pneumoniae, Pseudomonas fluorescens, Acinetobacter species, Vibrio species, Enterobacteriaceae species, and the genera Acinetobacter and Klebsiella. Transplant subjects also had increased proportions of Pseudomonas aeruginosa, Acinetobacter species, Enterobacteriaceae species, and Enterococcus faecalis, among other OTUs, while genera with increased proportions included Klebsiella, Acinetobacter, Staphylococcus, and Enterococcus. Furthermore, in transplant subjects, the dose of the immunosuppressant prednisone positively correlated with bacterial richness, while prednisone and mycophenolate mofetil doses positively correlated with the prevalence and proportions of transplant-associated taxa. Correlation network analysis of OTU relative abundance revealed a cluster containing potentially opportunistic pathogens as transplant associated. This cluster positively correlated with serum levels of C-reactive protein, suggesting a link between the resident flora at mucosal compartments and systemic inflammation. Network connectivity analysis revealed opportunistic pathogens as highly connected to each other and to common oral commensals, pointing to bacterial interactions that may influence colonization. This work demonstrates that immunosuppression aimed at limiting T-cell-mediated responses creates a more permissive oral environment for potentially opportunistic pathogens without affecting other members of the salivary bacteriome. PMID:23616410

Diaz, Patricia I; Hong, Bo-Young; Frias-Lopez, Jorge; Dupuy, Amanda K; Angeloni, Mark; Abusleme, Loreto; Terzi, Evimaria; Ioannidou, Effie; Strausbaugh, Linda D; Dongari-Bagtzoglou, Anna



Preoperative predictors of malignant gastric submucosal tumor  

PubMed Central

Purpose The preoperative prediction of malignant potential in patients with gastric submucosal tumors (SMTs) plays an important role in decisions regarding their surgical management. Methods We evaluated the predictors of malignant gastric SMTs in 314 patients with gastric SMTs who underwent surgery in Chonnam National University Hospital. Results The malignant SMTs were significantly associated with age (odds ratio [OR], 1.067; 95% confidence interval [CI], 1.042 to 1.091; P < 0.0001), presence of central ulceration (OR, 2.690; 95% CI, 1.224 to 5.909; P = 0.014), and tumor size (OR, 1.791; 95% CI, 1.483 to 2.164; P < 0.0001). Receiver operating characteristic curve analysis showed that tumor size was a good predictor of malignant potential. The most relevant predictor of malignant gastric SMT was tumor size with cut-offs of 4.05 and 6.40 cm. Conclusion Our findings indicated that age, central ulceration, and tumor size were significant preoperative predictors of malignant SMTs. We suggest that 4 cm be selected as a threshold value for malignant gastric SMTs. In patients with a gastric SMT larger than 4 cm with ulceration, wide resection of the full thickness of the gastric wall or gastrectomy with adequate margins should be performed because of its malignant potential.

Kim, Ho Goon; Ryu, Seong Yeob; Yun, Sang Kwon; Joo, Jae Kyoon; Lee, Jae Hyuk



The root bark of Paeonia moutan is a potential anticancer agent in human oral squamous cell carcinoma cells.  


Currently there is growing use of complementary and alternative anticancer medicines worldwide, and considerable interest in finding anticancer drugs among Chinese medicinal herbs. The aim of this study was to determine the antitumor activity of the root bark of Paeonia moutan (RBPM) in human squamous cell carcinoma (OSCC) cells. Cell lines derived from human oral squamous cell carcinoma (HSC2, 3, 4, SAS) were tested with different concentrations of RBPM (1-100 ?g/ml) using a series of in vitro assay systems. RBPM at a concentration of 100 ?g/ml inhibited monolayer and anchorage-independent growth, and interrupted coordinated migration. RBPM activated the phosphorylation of extracellular signal-regulated kinase (ERK) and serine/threonine kinase AKT in 30 min; then, at a later stage (after 6 hours) exhibited potent cytostatic, pro-apoptotic effects through the down-regulation of the expression of cyclin-dependent kinase 4 and its partner cyclin D1, and poly(ADP-ribose) polymerase cleavage. We found direct evidence that RBPM induces apoptotic cell death via DNA fragmentation. Taken together, the antitumor activity of RBPM was demonstrated through antiproliferative and apoptotic effects. PMID:22753719

Li, Chunnan; Yazawa, Kazunaga; Kondo, Seiji; Mukudai, Yoshiki; Sato, Daisuke; Kurihara, Yuji; Kamatani, Takaaki; Shintani, Satoru



Attitudes and Acceptance of Oral and Parenteral HIV Preexposure Prophylaxis among Potential User Groups: A Multinational Study  

Microsoft Academic Search

BackgroundThe use of antiviral medications by HIV negative people to prevent acquisition of HIV or pre-exposure prophylaxis (PrEP) has shown promising results in recent trials. To understand the potential impact of PrEP for HIV prevention, in addition to efficacy data, we need to understand both the acceptability of PrEP among members of potential user groups and the factors likely to

Andreas B. Eisingerich; Ana Wheelock; Gabriela B. Gomez; Geoffrey P. Garnett; Mark R. Dybul; Peter K. Piot



Oral Cancer Development in Patients with Leukoplakia - Clinicopathological Factors Affecting Outcome  

PubMed Central

Background Oral leukoplakia (OL) is the best-known potentially malignant disorder. The objective of the current study was to evaluate the clinicopathological factors predictive of outcome in a large cohort of patients with OL, and report our experience in the early detection of malignant events. Methods A total of 320 patients with biopsy-proven OL were retrospectively reviewed from the study institution who had a mean follow-up of 5.1 years. Data on patient and lesion at initial diagnosis and patient underwent sequential biopsies were reviewed. Multiple biopsies indicates >?=?3 times sequential biopsies. Oral cancer-free survival rate (OCFS) was determined by the Kaplan-Meier method and significant factors were identified by Cox regression analysis. Results The 3-year and 5-year OCFS was 86.6% and 82.0%, respectively. A new binary system of grading oral dysplasia was performed and Kaplan-Meier analysis indicated that high-grade dysplasia had significantly higher malignant incidence than low-grade dysplasia (5-year OCFS, 90.5% vs 59.0%; P<0.001), especially during the first 2–3 years of follow-up. Multivariate analysis revealed that the 4 factors including patient aged >60 years, lesion located at lateral/ventral tongue, non-homogenous lesion, high-grade dysplasia were independent significant indicators for OL malignant transformation. In addition, significant positive correlation between the multiple biopsies and these 4 factors and malignant outcome was established. Conclusions Elderly patients with OL located at lateral/ventral tongue and who had non-homogenous lesion with high-grade dysplasia correlated much higher risk of transformation. This high-risk subpopulation was suggested to undergo sequential biopsies and histologic examination contributing to early detection of malignant event.

Wu, Lan; Feng, Jin-Qiu; Yang, Xi; Li, Jiang; Zhou, Zeng-Tong; Zhang, Chen-Ping



Comparative study between the Hybrid Capture II test and PCR based assay for the detection of human papillomavirus DNA in oral submucous fibrosis and oral squamous cell carcinoma  

PubMed Central

Background Oral malignancy is a major global health problem. Besides the main risk factors of tobacco, smoking and alcohol, infection by human papillomavirus (HPV) and genetic alterations are likely to play an important role in these lesions. The purpose of this study was to compare the efficacy of HC-II assay and PCR for the detection of specific HPV type (HPV 16 E6) in OSMF and OSCC cases as well as find out the prevalence of the high risk HPV (HR-HPV) in these lesions. Methods and materials Four hundred and thirty patients of the potentially malignant and malignant oral lesions were taken from the Department of Otorhinolaryngology, Moti Lal Nehru Medical College, Allahabad, India from Sept 2007-March 2010. Of which 208 cases were oral submucous fibrosis (OSMF) and 222 cases were oral squamous cell carcinoma (OSCC). The HC-II assay and PCR were used for the detection of HR-HPV DNA. Result The overall prevalence of HR-HPV 16 E6 DNA positivity was nearly 26% by PCR and 27.4% by the HC-II assay in case of potentially malignant disorder of the oral lesions such as OSMF. However, in case of malignant oral lesions such as OSCC, 32.4% HPV 16 E6 positive by PCR and 31.4% by the HC-II assay. In case of OSMF, the two test gave concordant result for 42 positive samples and 154 negative samples, with an overall level of agreement of 85.4% (Cohen's kappa = 66.83%, 95% CI 0.553-0.783). The sensitivity and specificity of the test were 73.7% and 92.05% (p < 0.00). In case of OSCC, the two test gave concordant result for 61 positive samples and 152 negative samples, with an overall level of agreement of 88.3% (Cohen's kappa = 79.29, 95% CI 0.769-0.939) and the sensitivity and specificity of the test were 87.14% and 92.76% (p < 0.00). Conclusion This study concluded that slight difference was found between the positivity rate of HR-HPV infection detected by the HC-II and PCR assay in OSMF and OSCC cases and the HC II assay seemed to have better sensitivity in case of OSCC.



‘The Italian Protocol’: a simplified head-up tilt testing potentiated with oral nitroglycerin to assess patients with unexplained syncope  

Microsoft Academic Search

Head-up tilt testing potentiated by sublingual nitroglycerin (NTG), advocated by an Italian group, is a simple and safe but still not a standardized, diagnostic tool for the investigation of syncope. In fact, owing to its rapid spread, the original protocol received, often arbitrarily, many subsequent modifications. We now define the best methodology of the test on strictly evidence-based criteria as:

A. Bartoletti; P. Alboni; F. Ammirati; M. Brignole; A. Del Rosso; G. Foglia Manzillo; C. Menozzi; A. Raviele; R. Sutton



Studies on translocation, acute oral toxicity and intestinal colonization of potentially probiotic lactic acid bacteria administered during calf rearing  

Microsoft Academic Search

In order to test the harmlessness of potentially beneficial bacterial strains when raising young calves, their safety level should be verified before they are included into a probiotic formulation. In the present study, an inoculum composed of three lactic acid bacteria of bovine origin, Lactobacillus casei DSPV 318T, Lactobacillus salivarius DSPV 315T and Pediococcus acidilactici DSPV 006T, was evaluated to

L. S. Frizzo; E. Bertozzi; L. P. Soto; G. J. Sequeira; R. Rodriguez Armesto; M. R. Rosmini



Attitudes and Acceptance of Oral and Parenteral HIV Preexposure Prophylaxis among Potential User Groups: A Multinational Study  

PubMed Central

Background The use of antiviral medications by HIV negative people to prevent acquisition of HIV or pre-exposure prophylaxis (PrEP) has shown promising results in recent trials. To understand the potential impact of PrEP for HIV prevention, in addition to efficacy data, we need to understand both the acceptability of PrEP among members of potential user groups and the factors likely to determine uptake. Methods and findings Surveys of willingness to use PrEP products were conducted with 1,790 members of potential user groups (FSWs, MSM, IDUs, SDCs and young women) in seven countries: Peru, Ukraine, India, Kenya, Botswana, Uganda and South Africa. Analyses of variance were used to assess levels of acceptance across different user groups and countries. Conjoint analysis was used to examine the attitudes and preferences towards hypothetical and known attributes of PrEP programs and medications. Overall, members of potential user groups were willing to consider taking PrEP (61% reported that they would definitely use PrEP). Current results demonstrate that key user groups in different countries perceived PrEP as giving them new possibilities in their lives and would consider using it as soon as it becomes available. These results were maintained when subjects were reminded of potential side effects, the need to combine condom use with PrEP, and for regular HIV testing. Across populations, route of administration was considered the most important attribute of the presented alternatives. Conclusions Despite multiple conceivable barriers, there was a general willingness to adopt PrEP in key populations, which suggests that if efficacious and affordable, it could be a useful tool in HIV prevention. There would be a willingness to experience inconvenience and expense at the levels included in the survey. The results suggest that delivery in a long lasting injection would be a good target in drug development.

Gomez, Gabriela B.; Garnett, Geoffrey P.; Dybul, Mark R.; Piot, Peter K.



Activation of the canonical Wnt/?-catenin signalling pathway is rare in canine malignant melanoma tissue and cell lines.  


Canine malignant melanoma is a highly aggressive tumour associated with a poor overall survival rate due to both local disease recurrence and its highly metastatic nature. Similar to advanced melanoma in man, canine oral melanoma is poorly responsive to conventional anti-cancer therapies. The lack of sustainable disease control warrants investigation of novel therapies, preferably targeting features specific to the tumour and different from normal cells. The Wnt signalling pathway is known to contribute to melanocytic lineage development in vertebrates and perturbation of the Wnt/?-catenin pathway has been implicated in numerous cancer types. Alterations of the Wnt/?-catenin pathway are suggested to occur in a subset of human melanomas, although the precise role of the Wnt/?-catenin pathway in melanoma is yet to be defined. This study investigates the activation status of the canonical Wnt/?-catenin pathway in canine malignant melanoma and its potential as a therapeutic target for treating this disease. The data indicate that canonical Wnt/?-catenin pathway activation is a rare event in canine oral malignant melanoma tissue and canine malignant melanoma cell lines. PMID:22901430

Chon, E; Thompson, V; Schmid, S; Stein, T J



The potential of organic-based amylose-ethylcellulose film coatings as oral colon-specific drug delivery systems  

Microsoft Academic Search

Amylose-ethylcellulose film coatings obtained from organic-based solvents were investigated as potential vehicles for colonic\\u000a drug delivery. Amylose, in the form of an amylose-butan-1-ol dispersion, and ethylcellulose, dissolved in either ethyl lactate,\\u000a ethanol, or propanol and plasticized with dibutyl sebacate, were mixed in various proportions and applied using a fluidized\\u000a bed coater to achieve a range of film thicknesses on 5-aminosalicylic

Lee F. Siew; Abdul W. Basit; J. Michael Newton



Anogenital malignancies and pre-malignancies.  


Anogenital pre-malignancies and malignancies are frequently encountered. Aetiopathogenetically, human papillomavirus (HPV) infection plays a critical role. However, there is a variable degree of association of HPV infection with the development of anogenital malignancies. In this context, the high level of clinically unapparent HPV infection should be considered. Therefore, the question arises if the association with HPV is always causative. Besides HPV, pre-existent lichen sclerosus is also an important aetiopathologic factor in the development of anogenital malignancies. Common anogenital pre-malignancies comprise Bowen's disease (BD), Bowenoid papulosis (BP) and erythroplasia of Queyrat (EQ). From a clinical point of view, these are clearly different entities, but from a histopathological point of view, BD, BP and EQ are indistinguishable. They all represent forms of squamous intraepithelial neoplasia (IN). Intraepithelial neoplasia (IN) is not only restricted to squamous variants, but also includes non-squamous IN, Paget's disease (PD) and melanoma in situ. The risk of developing anogenital (pre)malignancies or other tumours is higher in immunocompromised and immunodeficient patients, in particular those suffering from human immunodeficiency virus (HIV) infection. Such risk factors will affect treatment and follow-up modalities. Regarding prophylactic measures, a relatively recent but very important development is the availability of HPV vaccination on a large scale. Momentarily, the effects of such vaccination, on a population-based scale, are not yet clear but will become apparent in the near future. Management of anogenital pre-malignancies and malignancies should be tailor-made and may be organized in a multidisciplinary fashion. PMID:21272092

Henquet, C J M



Oral microbiome and oral and gastrointestinal cancer risk  

PubMed Central

A growing body of evidence implicates human oral bacteria in the etiology of oral and gastrointestinal cancers. Epidemiological studies consistently report increased risks of these cancers in men and women with periodontal disease or tooth loss, conditions caused by oral bacteria. More than 700 bacterial species inhabit the oral cavity, including at least 11 bacterial phyla and 70 genera. Oral bacteria may activate alcohol and smoking-related carcinogens locally or act systemically, through chronic inflammation. High-throughput genetic-based assays now make it possible to comprehensively survey the human oral microbiome, the totality of bacteria in the oral cavity. Establishing the association of the oral microbiome with cancer risk may lead to significant advances in understanding of cancer etiology, potentially opening a new research paradigm for cancer prevention.

Chen, Calvin Y.; Hayes, Richard B.



Cutaneous manifestations of systemic malignancies: part 2.  


The skin can be key to early diagnosis of systemic malignancies. In the second part of this review, we present various skin conditions that can, in certain contexts, reveal the presence of malignancy. The skin conditions are presented in groups based on a diverse range of morphological characteristics. Specifically, the following groups are analyzed: erosive and blistering lesions; inflammatory papules and nodules; xerosis, ichthyosis, and generalized exfoliative dermatitis; symptoms such as pruritus; abnormal hair distribution patterns; sweating disorders; benign tumors that can form part of hereditary syndromes associated with a risk of visceral cancer; and finally, oral and nail abnormalities. This review highlights the importance of the skin in the study of systemic malignancies. PMID:23891448

Yuste Chaves, M; Unamuno Pérez, P



Oral mucosal immunity.  


Oral keratinocytes and dendritic cells of the oral mucosa, through molecular pattern recognition receptors, distinguish between commensal and pathogenic microorganisms and mediate the generation of protective immunoinflammatory responses to potentially invading pathogens or mediate immune tolerance toward commensal microorganisms. Oral immune tolerance is the result either of lack of activation of T cells in response to immunogenic presentation of antigens or of suppression of activity of effector T cells by regulatory T cells. Secretory immunoglobulin A (sIgA) antibodies at oral mucosal sites contribute to oral immunity by limiting colonization of microorganisms and their invasion of the epithelium. Ig isotype class switching to IgA is either dependent on or independent of T helper cells and is facilitated by cytokines secreted by dendritic cells and monocytes. PMID:24119522

Feller, L; Altini, M; Khammissa, R A G; Chandran, R; Bouckaert, M; Lemmer, J



Oral Insulin  

Microsoft Academic Search

Oral insulin is an exciting area of research and development in the field of diabetology. This brief review covers the various approaches used in the development of oral insulin, and highlights some of the recent data related to novel oral insulin preparation.

Sanjay Kalra; Bharti Kalra; Navneet Agrawal



Why only areca nut chewing cannot cause oral submucous fibrosis?  


Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral cavity. Most of the affected people are betel quid chewers. Although, betel quid is consumed in various forms, only areca nut chewing habit has become very rare. We came across 34 such cases with 32 showing no evidence of OSF. Therefore, we hypothesize that only areca nut chewing cannot cause OSF and presence of other factors like slaked lime and inflammation is necessary. Keeping in mind the composition of areca nut, hypothesis is comprehensively discussed at molecular level in the present paper with special emphasis on the role of TGF-beta and lysyl oxidase enzyme in OSF. If investigated in the suggested direction, it might provide an important clue about the pathogenesis of OSF and thus can help in the future development of treatment strategies. PMID:23602208

Sarode, Sachin C; Mahuli, Amit; Sarode, Gargi S; Mahuli, Simpy



Proposed clinical classification for oral submucous fibrosis.  


Oral Submucous Fibrosis (OSMF) is a chronic, progressive, scarring disease, that predominantly affects people of South Asia and South-East Asia, where chewing of arecanut and its commercial preparation is high. Presence of fibrous bands is the main characteristic feature of OSMF. Based on clinical and/or histopathological features of OSMF, various classifications have been put forth till date. But the advantages and drawbacks of these classification supersedes each other, leading to perplexity. Our various studies and clinical experience in the field of OSMF have initiated us to propose/introduce the new clinical classification which could assist the clinician in the categorization of this potentially malignant disorder according to its biological behaviour and hence its subsequent medical and surgical management. PMID:22070918

More, Chandramani B; Das, Sunanda; Patel, Hetul; Adalja, Chhaya; Kamatchi, Vaishnavee; Venkatesh, Rashmi



The transmembrane adaptor Cbp/PAG1 controls the malignant potential of human non-small cell lung cancers that have c-src upregulation.  


The tyrosine kinase c-Src is upregulated in various human cancers, although the precise regulatory mechanism underlying this upregulation is unclear. We previously reported that a transmembrane adaptor Csk-binding protein (Cbp; PAG1) plays an important role in controlling the cell transformation that is induced by the activation of c-Src. To elucidate the in vivo role of Cbp, we examined the function of Cbp in lung cancer cell lines and tissues. In this study, we found that Cbp was markedly downregulated in human non-small cell lung cancer (NSCLC) cells. The ectopic expression of Cbp suppressed the anchorage-independent growth of the NSCLC cell lines (A549 and Lu99) that had upregulated c-Src, whereas the Cbp expression had little effect on other NSCLC cell lines (PC9 and Lu65) that express normal levels of c-Src. The expression of Cbp suppressed the kinase activity of c-Src in A549 cells by recruiting c-Src and its negative regulator, C-terminal Src kinase (Csk), to lipid rafts. The treatment with Src inhibitors, such as PP2, dasatinib, and saracatinib, also suppressed the growth of A549 cells. Furthermore, Cbp expression attenuated the ability of A549 cells to form tumors in nude mice, invade in vitro, and metastasize in vivo. In addition, we found a significant inverse correlation between the level of Cbp expression and the extent of lymph node metastasis in human lung cancers. These results indicate that Cbp is required for the Csk-mediated inactivation of c-Src and may control the promotion of malignancy in NSCLC tumors that are characterized by c-Src upregulation. PMID:21156787

Kanou, Takashi; Oneyama, Chitose; Kawahara, Kunimitsu; Okimura, Akira; Ohta, Mitsunori; Ikeda, Naoki; Shintani, Yasushi; Okumura, Meinoshin; Okada, Masato



Myb overexpression overrides androgen depletion-induced cell cycle arrest and apoptosis in prostate cancer cells, and confers aggressive malignant traits: potential role in castration resistance  

PubMed Central

Myb, a cellular progenitor of v-Myb oncogenes, is amplified in prostate cancer and exhibits greater amplification frequency in hormone-refractory disease. Here, we have investigated the functional significance of Myb in prostate cancer. Our studies demonstrate Myb expression in all prostate cancer cell lines (LNCaP, C4-2, PC3 and DU145) examined, whereas it is negligibly expressed in normal/benign prostate epithelial cells (RWPE1 and RWPE2). Notably, Myb is significantly upregulated, both at transcript (>60-fold) and protein (>15-fold) levels, in castration-resistant (C4-2) cells as compared with androgen-dependent (LNCaP) prostate cancer cells of the same genotypic lineage. Using loss and gain of function approaches, we demonstrate that Myb promotes and sustains cell cycle progression and survival under androgen-supplemented and -deprived conditions, respectively, through induction of cyclins (A1, D1 and E1), Bcl-xL and Bcl2 and downregulation of p27 and Bax. Interestingly, Myb overexpression is also associated with enhanced prostate-specific antigen expression. Furthermore, our data show a role of Myb in enhanced motility and invasion and decreased homotypic interactions of prostate cancer cells. Myb overexpression is also associated with actin reorganization leading to the formation of filopodia-like cellular protrusions. Immunoblot analyses demonstrate gain of mesenchymal and loss of epithelial markers and vice versa, in Myb-overexpressing LNCaP and -silenced C4-2 cells, respectively, indicating a role of Myb in epithelial to mesenchymal transition. Altogether, our studies provide first experimental evidence for a functional role of Myb in growth and malignant behavior of prostate cancer cells and suggest a novel mechanism for castration resistance.

Srivastava, Sanjeev K.; Bhardwaj, Arun; Arora, Sumit; McClellan, Steven; Grizzle, William E.; Reed, Eddie; Singh, Ajay P.



Malondialdehyde Levels in Oral Sub Mucous Fibrosis: A Clinicopathological and Biochemical Study  

PubMed Central

Background: Oral submucous fibrosis is one of the most commonly occurring potentially malignant disorders in the South-East Asia. Levels of lipid peroxidation product malondialdehyde have been recently correlated with clinical grades of oral Submucous fibrosis. Aims: The aims of this study were to estimate the levels of malondialdehyde in serum, saliva and tissue in patients with oral submucous fibrosis, to correlate change in levels of malodialdehyde with the histopathological grading. Materials and Methods: The study group comprised of 65 clinically diagnosed and histopathologically confirmed cases of oral submucous fibrosis, 21 age and sex matched controls were also enrolled into the study. The serum saliva and tissue samples in the study groups were evaluated by the thiobarbutric acid reactive substances. Results: There was a significant difference between the serum and salivary malondialdehyde among the histopathological grades of oral submucous fibrosis. Tissue malonaldehyde levels were significantly higher as the grading progressed but tissue levels in grade 3 oral submucous fibrosis were lower than the controls. Conclusion: This decrease in tissue malonaldehyde could possibly be associated to collagen cross linking occurring during the advanced stages of oral submucous fibrosis.

Shetty, Shishir Ram; Babu, Subhas G; Kumari, Suchetha; Rao, Vaman; Vijay, R; Karikal, Arvind



Olanzapine induced neuroleptic malignant syndrome  

PubMed Central

An 18 year old male diagnosed as a case of bipolar affective disorder (BPAD), developed neuroleptic malignant syndrome (NMS) following treatment with olanzapine (20 mg per day), an atypical antipsychotic drug. NMS is usually seen with typical antipsychotic drugs. The patient was diagnosed as a case of NMS, offending agent was immediately withdrawn and prompt treatment with bromocriptine and levodopa produced a good recovery. The various features of the case are discussed in view of the potential mortality of the syndrome.

Patra, Bichitra Nanda; Khandelwal, Sudhir K.; Sood, Mamta



Sialidase and malignancy: A minireview  

Microsoft Academic Search

Aberrant sialylation in cancer cells is thought to be a characteristic feature associated with malignant properties including\\u000a invasiveness and metastatic potential. Sialidase which catalyzes the removal of sialic acid residues from glycoproteins and\\u000a glycolipids, has been suggested to play important roles in many biological processes through regulation of cellular sialic\\u000a acid contents. The altered expression of sialidase observed in cancer

Taeko Miyagi; Tadashi Wada; Kazunori Yamaguchi; Keiko Hata



Rheumatic Diseases and Malignancies  

PubMed Central

ABSTRACT There are many studies which demonstrate a higher risk for malignancy in patients with rheumatic diseases. There have been a number of possible explanations for the differences in the risk of certain malignancies in patients with rheumatic disease, compared with general population, but a clear mechanism is difficult to identify. Rheumatoid syndromes may be associated with malignancy as paraneoplastic conditions, which can antedate the neoplasm diagnosis. On the other hand, autoimmune rheumatic diseases have a higher risk of malignancy by themselves or because of the immunosuppressant treatments.

BOJINCA, Violeta; JANTA, Iustina



The potential of organic-based amylose-ethylcellulose film coatings as oral colon-specific drug delivery systems.  


Amylose-ethylcellulose film coatings obtained from organic-based solvents were investigated as potential vehicles for colonic drug delivery. Amylose, in the form of an amylose-butan-1-ol dispersion, and ethylcellulose, dissolved in either ethyl lactate, ethanol, or propanol and plasticized with dibutyl sebacate, were mixed in various proportions and applied using a fluidized bed coater to achieve a range of film thicknesses on 5-aminosalicylic acid pellets. Drug release from the coated pellets was assessed under gastric and small intestinal conditions in the presence and absence of pepsin and pancreatin using dissolution methodology, and also within a simulated colonic environment involving fermentation testing with human feces in the form of a slurry. Under upper gastrointestinal tract conditions, the rate and extent of drug release were found to be related to the thickness of the coating and the ratio of amylose to ethylcellulose within the film. Modeling of the drug release data revealed that the ratio was more important than coat thickness in controlling drug release, irrespective of the solvent used for coating. Coatings with a thick film and/or low amylose content were relatively impermeable and able to delay drug release under conditions mimicking the upper gastrointestinal tract. Furthermore, drug release was unaffected by the presence of pepsin and pancreatin and by long-term storage. Under simulated colonic conditions, drug release was more pronounced from coating formulations containing higher proportions of amylose. Colon-specificity can therefore be achieved using such systems by judicious choice of the appropriate ratio of amylose to ethylcellulose and coat thickness. PMID:14727908

Siew, L F; Basit, A W; Newton, J M



Malignant mesothelioma: attributable risk of asbestos exposure  

Microsoft Academic Search

OBJECTIVES--To evaluate a case-control study of malignant mesothelioma through patterns of exposure to asbestos based upon information from telephone interviews with next of kin. METHODS--Potential cases, identified from medical files and death certificates, included all people diagnosed with malignant mesothelioma and registered during 1975-1980 by the Los Angeles County Cancer Surveillance Program, the New York State Cancer Registry (excluding New

R Spirtas; E F Heineman; L Bernstein; G W Beebe; R J Keehn; A Stark; B L Harlow; J Benichou



The potential of Lactobacillus as a carrier for oral immunization: Development and preliminary characterization of vector systems for targeted delivery of antigens  

Microsoft Academic Search

Oral administration of lactobacilli evokes mucosal and systemic immune responses against epitopes associated with these organisms (Gerritse et al., 1990, 1991). The adjuvant function of different Lactobacillus species was investigated under the conditions of intraperitoneal (i.p.) injection or oral administration. After i.p. injection of trinitrophenylated chicken ?-globulin, high DTK responses were observed with Lactobacillus casei and Lactobacillus plantarum, but low

Peter H. Pouwels; Rob J. Leer; Wim J. A. Boersma



Introduction of low dose transdermal buprenorphine -- did it influence use of potentially addictive drugs in chronic non-malignant pain patients?  


The aim was to study the introduction of the new low dose transdermal buprenorphine (LD-TD-BUP) in Norway, particularly with regard to former use and co-medication with other potentially addictive drugs. The nationwide Norwegian Prescription Database contains information on all prescription drugs dispensed to individual non-institutionalised patients, and we may follow all individuals who received LD-TD-BUP (Norspan) after marketing on the Norwegian market on 15/11/05. We studied all prescriptions of opioids and other potentially addictive drugs to patients receiving at least two LD-TD-BUP prescriptions during 2004-2006. Poisson regressions were run with concomitant use of addictive drugs (yes, no) as the endpoint. Overall, 1884, non cancer individuals received at least two prescription of LD-TD-BUP. Of these 91.7% received prescriptions of other opioids and 58.6% of them had also been prescribed benzodiazepines/carisoprodol before the prescription of LD-TD-BUP. Of the LD-TD-BUP users who received more than one prescription, 60% co-medicated with at least one other potentially addictive drug, and 24% with at least two. In the multivariate analysis, the variables associated with a higher likelihood of using co-medicated drugs were: previous use of benzodiazepines/carisoprodol relative risk RR=16.7 (95% CI 10.4-26.9), previous use of opioids RR=4.0 (1.9-8.7) and younger age 20-40 years RR=1.9 (1.6-2.3). So far, it is questionable whether the introduction of LD-TD-BUP actually has stabilised opioids consumption or whether it has complicated and increased the consumption of potentially addictive drugs. PMID:19095476

Skurtveit, Svetlana; Furu, Kari; Kaasa, Stein; Borchgrevink, Petter C



A novel multiplex assay combining autoantibodies plus PSA has potential implications for classification of prostate cancer from non-malignant cases  

Microsoft Academic Search

Background  The lack of sufficient specificity and sensitivity among conventional cancer biomarkers, such as prostate specific antigen\\u000a (PSA) for prostate cancer has been widely recognized after several decades of clinical implications. Autoantibodies (autoAb)\\u000a among others are being extensively investigated as potential substitute markers, but remain elusive. One major obstacle is\\u000a the lack of a sensitive and multiplex approach for quantifying autoAb

Chong Xie; Hyun J Kim; Jonathan G Haw; Anusha Kalbasi; Brian K Gardner; Gang Li; Jianyu Rao; David Chia; Monty Liong; Rubio R Punzalan; Leonard S Marks; Allan J Pantuck; Alexandre de la Taille; Guomin Wang; Hideki Mukouyama; Gang Zeng



Aberrant Expression of a Disintegrin and Metalloproteinase 17\\/Tumor Necrosis Factor-A Converting Enzyme Increases the Malignant Potential in Human Pancreatic Ductal Adenocarcinoma  

Microsoft Academic Search

A disintegrin and metalloproteinase (ADAM) molecules are known for their unique potential to combine adhesion, proteolysis, and signaling. To understand the role of AD- AM17\\/tumor necrosis factor-A (TNF-A) converting enzyme (TACE) in pancreatic ductal adenocarcinoma (PDAC), we investigated its expression, function, and in vitro regulation. ADAM17\\/TACE mRNA was expressed in 3 of 10 normal pancreatic tissues, 6 of 8 samples

Jorg Ringel; Ralf Jesnowski; Nicolas Moniaux; Jutta Luttges; Jens Ringel; Amit Choudhury; Surinder K. Batra; Gunter Kloppel; Matthias Lohr


Recovery and screening for antibiotic susceptibility of potential bacterial pathogens from the oral cavity of shark species involved in attacks on humans in Recife, Brazil.  


The number of incidents involving sharks and humans at beaches in Recife, on the north-eastern Brazilian coast, is among the highest worldwide. In addition, wound infections in survivors are common; but the nature and risk of the aetiological agents is unknown. In the present study, 81 potential bacterial pathogens were identified in the oral cavity of sharks involved in attacks in Recife, and were subjected to antibiotic susceptibility tests using the standardized disc-diffusion method. The majority were enterobacteria such as Enterobacter spp., Citrobacter spp., Proteus spp., Providencia alcalifaciens, Escherichia coli, Moellerella wisconcensis and Leclercia adecarboxylata. Other Gram-negative bacteria included Vibrio spp., Burkholderia cepacia, Acinetobacter spp. and Pseudomonas spp. In addition, coagulase-positive and coagulase-negative Staphylococcus spp., Enterococcus spp. and Micrococcus spp. were identified, besides Streptococcus spp. from the viridans group. Resistance was especially found in the Proteus mirabilis and Citrobacter freundii, and ranged from 4 to 6 antibiotics out of the 13 tested. Gentamicin and vancomycin were the most effective against Gram-positive cocci strains, whereas levofloxacin was fully inhibitory against Gram-positive and Gram-negative bacteria. These data are discussed in light of a retrospective evaluation of the medical records of three shark victims treated at Restauração Hospital in Recife. PMID:20413619

Interaminense, J A; Nascimento, D C O; Ventura, R F; Batista, J E C; Souza, M M C; Hazin, F H V; Pontes-Filho, N T; Lima-Filho, J V



Malignancy in pregnancy  

Microsoft Academic Search

Malignant disease in pregnancy represents a complex situation with medical and ethical issues. Delayed diagnosis occurs when symptoms are attributed to pregnancy. Once malignancy is diagnosed, gestational age becomes important in further management. Magnetic resonance imaging is safe in pregnancy and can be used for staging purposes. Maternal counselling is of paramount importance in decision-making.

Saadiya Aziz Karim; Mahmood I. Shafi



AIDS-Related Malignancies  

Microsoft Academic Search

OVERVIEW OF MALIGNANCY IN PATIENTS WITH AIDS Despite the advent of highly active antiretroviral therapy, the incidence of human immunodeficiency virus (HIV)-asso- ciated malignancies has not decreased. The United States Centers for Disease Control (CDC) has determined that Kaposi's sarcoma, non-Hodgkin's lymphoma (including pri- mary central nervous system lymphoma), and cervical carci- noma define the acquired immune deficiency syndrome (AIDS).



AIDS and associated malignancies  

Microsoft Academic Search

AIDS associated malignancies (ARL) is a major complication associated with AIDS patients upon immunosuppression. Chronically immunocompromised patients have a markedly increased risk of developing lymphoproliferative disease. In the era of potent antiretrovirals therapy (ARV), the malignant complications due to HIV-1 infection have decreased in developed nations where ARV is administered, but still poses a major problem in developing countries where

Charles WOOD; William HARRINGTON



[Primary malignant bone tumors].  


Among human neoplasms, primary malignant bone tumors are fairly rare. They present an incidence rate of roughly 10 cases per 1 million inhabitants per year. During childhood (<15 years), the percentage of malignant bone tumors amounts to 6% of all infantile malignancies. Only leukemia and lymphoma show a higher incidence in adolescence. Of all primary malignant bone tumors, 60% affect patients younger than 45 years and the peak incidence of all bone tumors occurs between 15 and 19 years. The most common primary malignant bone tumors are osteosarcoma (35%), chondrosarcoma (25%), and Ewing's sarcoma (16%). Less frequently (??5%) occurring tumors are chordoma, malignant fibrous histiocytoma of bone, and fibrosarcoma of bone. Vascular primary malignant tumors of bone and adamantinoma are very rare. Staging of the lesion is essential for systemic therapeutic decision-making and includes complete imaging and histo-pathological confirmation of the suspected entity. In most cases, this is established by open- or image-guided biopsy. Based on this information, an interdisciplinary tumor board will determine the individual therapeutic approach. Endoprosthetic or biological reconstruction following wide tumor resection is the most common surgical therapy for primary malignant bone tumors. There is vital importance in a thorough postoperative follow-up and continous after-care by a competent tumor center which is permanentely in charge of therapy. PMID:22130624

von Eisenhart-Rothe, R; Toepfer, A; Salzmann, M; Schauwecker, J; Gollwitzer, H; Rechl, H



Screening for Malignant Hyperpyrexia  

Microsoft Academic Search

The methods used to screen patients for malignant hyperpyrexia at present are not sufficiently accurate. This paper reports more specific methods of detecting patients liable to develop malignant hyperpyrexia. A motor-point muscle biopsy is performed for histopathological examination and to detect muscle contracture in vitro after exposure to halothane and suxamethonium.

F. Richard Ellis; Niall P. Keaney; D. G. F. Harriman; D. W. Sumner; K. Kyei-Mensah; J. H. Tyrrell; J. B. Hargreaves; R. K. Parikh; P. L. Mulrooney



Malignant pleural disease  

Microsoft Academic Search

The vast majority of pleural neoplasms invade the pleura secondarily and can be seen in patients with bronchogenic carcinoma, breast cancer, lymphoma, and ovarian or gastric carcinoma. Primary pleural neoplasms are less common, although they have developed notoriety since the up-surge of malignant mesothelioma and the knowledge of its connection to asbestos exposure. Other malignant primary tumors include localized fibrous

Lorenzo Bonomo; Beatrice Feragalli; Rocco Sacco; Biagio Merlino; Maria Luigia Storto



Malignant sinonasal epithelioid schwannoma  

Microsoft Academic Search

Malignant schwannomas are rare neoplasms that are seldom found in the head and neck. Few cases have been reported involving paranasal sinuses and none of them was of the “epithelioid” type, In this report, an unusual case of epithelioid malignant schwannoma involving the maxillary sinus, nasal cavity and orbit is presented. The patient was a 27-year-old male with a history

Pedro L. Fernández; Antonio Cardesa; Josep A. Bombí; Antonio Palacín; Josep Traserra



Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential.  


Boron neutron capture therapy (BNCT) combines selective accumulation of (10)B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na(3) [ae-B(20)H(17)NH(3)], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 ± 16.1 ppm at 48 h and to 43.9 ± 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3. PMID:22271404

Heber, Elisa M; Kueffer, Peter J; Lee, Mark W; Hawthorne, M Frederick; Garabalino, Marcela A; Molinari, Ana J; Nigg, David W; Bauer, William; Hughes, Andrea Monti; Pozzi, Emiliano C C; Trivillin, Verónica A; Schwint, Amanda E



Venous thromboembolism in malignant gliomas  

PubMed Central

Summary Malignant gliomas are associated with a very high risk of venous thromboembolism (VTE). While many clinical risk factors have previously been described in brain tumor patients, the risk of VTE associated with newer anti-angiogenic therapies such as bevacizumab in these patients remains unclear. When VTE occurs in this patient population, concern regarding the potential for intracranial hemorrhage complicates management decisions regarding anticoagulation, and these patients have a worse prognosis than their VTE-free counterparts. Risk stratification models identifying patients at high risk of developing VTE along with predictive plasma biomarkers may guide the selection of eligible patients for primary prevention with pharmacologic thromboprophylaxis. Recent studies exploring disordered coagulation, such as increased expression of tissue factor (TF), and tumorigenic molecular signaling may help to explain the increased risk of VTE in patients with malignant gliomas.




Radiation Therapy for Malignant Mesothelioma  


... malignant mesothelioma Next Topic Chemotherapy for malignant mesothelioma Radiation therapy for malignant mesothelioma Radiation therapy uses high- ... this form of treatment more useful. Uses of radiation therapy Radiation therapy may be used in different ...


Identification of endoplasmic reticulum stress-inducing agents by antagonizing autophagy: a new potential strategy for identification of anti-cancer therapeutics in B-cell malignancies.  


The endoplasmic reticulum (ER) plays a vital function in multiple cellular processes. There is a growing interest in developing therapeutic agents that can target the ER in cancer cells, inducing a stress response that leads to cell death. However, ER stress-inducing agents can also induce autophagy, a survival strategy of cancer cells. Therefore, by inhibiting autophagy we can increase the efficacy of the ER stress-inducing agents. Nelfinavir, a human immunodeficiency virus (HIV) protease inhibitor with anti-cancer properties, can induce ER stress. Nelfinavir's effects on chronic lymphocytic leukemia (CLL) are yet to be elucidated. Herein we demonstrate that nelfinavir induces ER morphological changes and stress response, along with an autophagic protective strategy. Our data reveal that chloroquine, an autophagy inhibitor, significantly increases nelfinavir cytotoxicity. These results identify a novel strategy potentially effective in CLL treatment, by repositioning two well-known drugs as a combinatorial therapy with anti-cancer properties. PMID:23469959

Mahoney, Emilia; Maddocks, Kami; Flynn, Joseph; Jones, Jeffrey; Cole, Sara L; Zhang, Xiaoli; Byrd, John C; Johnson, Amy J



Better grade of tumor differentiation of oral squamous cell carcinoma arising in background of oral submucous fibrosis.  


Oral submucous fibrosis (OSMF) is a potentially malignant disorder of the oral cavity. Most of the people affected by OSMF are betel quid chewers. It is characterized by epithelial atrophy and progressive accumulation of collagen fibers in lamina propria and submucosa of the oral mucosa. 7.6% of OSMF cases undergo oral squamous cell carcinoma (OSCC) transformation of which majority display low grade of tumor differentiation. In the present paper, a hypothesis has been proposed to correlate atrophy, turnover rate and surface keratization in OSMF with degree of tumor differentiation in OSCC. A novel hypothesis for epithelial atrophy in OSMF has also been emphasized. High proliferative activity and basal cell hyperplasia in conjunction with rapid exfoliation of superficial cells and epithelial atrophy suggest that epithelial turnover rate is very high in OSMF. Presence of surface keratinized layer in this situation suggests faster maturation or differentiation of epithelium in OSMF. Thus, the epithelial cells are genetically programmed for high turnover rate and faster differentiation or maturation to form keratin. During malignant transformation of OSMF, the transformed epithelial cells may retain the genetic memory of faster differentiation and maturation resulting in better grade of tumor differentiation. The well differentiated OSCC has good prognosis, better survival rate and less chances of recurrence of regional and distant metastasis. Studies are needed to explore the biomarkers or molecular markers associated with carcinogenesis like genetic instability, oncogenes, tumor suppressor genes and angiogenesis in OSCC associated with OSMF. If investigated in the suggested direction, it might provide some important clues about the pathogenesis of OSCC arising in background of OSMF and for the future development of treatment strategies. PMID:23891040

Sarode, Sachin C; Sarode, Gargi S



Oral Cancer  


... the mouth. Anyone can get oral cancer, but the risk is higher if you are male, over age 40, use tobacco or alcohol or have a history of head or neck cancer. Frequent sun exposure is also a risk for lip cancer. Symptoms of oral ...


Oral complications in cancer patients  

SciTech Connect

Ionizing radiation used in treating the head and neck area produces oral side effects such as mucositis, salivary changes, trismus and radiation caries. Sequelae of cancer chemotherapy often include oral stomatitis, myelosuppression and immunosuppression. Infections of dental origin in compromised patients are potentially lethal. Specific programs to eliminate dental pathology before radiation and chemotherapy, and to maintain oral hygiene during and after therapy, will minimize these complications.

Carl, W.



The sensitivity and specificity of computerized brush biopsy and scalpel biopsy in diagnosing oral premalignant lesions: A comparative study  

PubMed Central

Background: The diagnosis of oral malignancy and epithelial dysplasia has traditionally been based upon histopathological evaluation of full thickness biopsy from lesional tissue. As many studies had shown that incisional biopsy could cause progression of the tumors, many alternative methods of collection of samples had been tested. Oral brush biopsy is a transepithelial biopsy where it collects cells from basal cell layer noninvasively. Aim: To assess the diagnostic accuracy of brush biopsy when compared to histopathology in a group of patients with features of potentially malignancy. Materials and Methods: In the present study, 60 cases of clinically diagnosed leukoplakia are selected and subjected to histopathology and brush biopsy. Results and Conclusion: Results showed that of 16 dysplasia cases confirmed by histopathology, only 12 were positively reported in oral brush biopsy. In 44 cases, the reports are same for histopathology and brush biopsy. The sensitivity of oral brush biopsy is 43.5% and specificity is 81.25% with a positive predictive value of 58.3%. Oral brush biopsy with molecular markers like tenascin and keratins can be an accurate diagnostic test.

Reddy, Sridhar G; Kanala, Surekha; Chigurupati, Anuradha; Kumar, Shamala Ravi; Poosarla, Chandhra Sekhar; Reddy, B Venkata Ramana



New Potential Therapeutic Approach for the Treatment of B-Cell Malignancies Using Chlorambucil/Hydroxychloroquine-Loaded Anti-CD20 Nanoparticles  

PubMed Central

Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders.

Mezzaroba, Nelly; Zorzet, Sonia; Secco, Erika; Biffi, Stefania; Tripodo, Claudio; Calvaruso, Marco; Mendoza-Maldonado, Ramiro; Capolla, Sara; Granzotto, Marilena; Spretz, Ruben; Larsen, Gustavo; Noriega, Sandra; Lucafo, Marianna; Mansilla, Eduardo; Garrovo, Chiara; Marin, Gustavo H.; Baj, Gabriele; Gattei, Valter; Pozzato, Gabriele; Nunez, Luis; Macor, Paolo



New Potential Therapeutic Approach for the Treatment of B-Cell Malignancies Using Chlorambucil/Hydroxychloroquine-Loaded Anti-CD20 Nanoparticles.  


Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders. PMID:24098639

Mezzaroba, Nelly; Zorzet, Sonia; Secco, Erika; Biffi, Stefania; Tripodo, Claudio; Calvaruso, Marco; Mendoza-Maldonado, Ramiro; Capolla, Sara; Granzotto, Marilena; Spretz, Ruben; Larsen, Gustavo; Noriega, Sandra; Lucafò, Marianna; Mansilla, Eduardo; Garrovo, Chiara; Marín, Gustavo H; Baj, Gabriele; Gattei, Valter; Pozzato, Gabriele; Núñez, Luis; Macor, Paolo



Evaluation of an Attenuated Vesicular Stomatitis Virus Vector Expressing Interferon-? for Use in Malignant Pleural Mesothelioma: Heterogeneity in Interferon Responsiveness Defines Potential Efficacy  

PubMed Central

Abstract Vesicular stomatitis virus (VSV) has shown promise as an oncolytic agent, although unmodified VSV can be neurotoxic. To avoid toxicity, a vector was created by introducing the interferon-? (IFN-?) gene (VSV.IFN-?). We conducted this study to determine the ability of VSV.IFN-? to lyse human cancer (mesothelioma) cells and to evaluate the potential of this recombinant virus for clinical translation. Four normal human mesothelial and 12 mesothelioma cell lines were tested for their susceptibility to VSV vectors in vitro. VSV.hIFN-? did not cause cytotoxicity in any normal lines. Only 4 of 12 lines were effectively lysed by VSV.hIFN-?. In the eight resistant lines, pretreatment with IFN-? prevented lysis of cells by VSV.GFP, and VSV infection or addition of IFN-? protein resulted in the upregulation of double-stranded RNA-dependent protein kinase (PKR), myxovirus resistance A (MxA), and 2?,5?-oligo-adenylate-synthetase (2?5?-OAS) mRNA. In the susceptible lines, there was no protection by pretreatment with IFN-? protein and no IFN- or VSV-induced changes in PKR, MxA, and 2?5?-OAS mRNA. This complete lack of IFN responsiveness could be explained by marked downregulation of interferon alpha receptors (IFNARs), p48, and PKR in both the mesothelioma cell lines and primary tumor biopsies screened. Presence of p48 in three tumor samples predicted responsiveness to IFN. Our data indicate that many mesothelioma tumors have partially intact IFN pathways that may affect the efficacy of oncolytic virotherapy. However, it may be feasible to prescreen individual susceptibility to VSV.IFN-? by immunostaining for the presence of p48 protein.

Saloura, Vassiliki; Wang, Liang-Chuan S.; Fridlender, Zvi G.; Sun, Jing; Cheng, Guanjun; Kapoor, Veena; Sterman, Daniel H.; Harty, Ronald N.; Okumura, Atsushi; Barber, Glen N.; Vile, Richard G.; Federspiel, Mark J.; Russell, Stephen J.; Litzky, Leslie



Aberrant expression of a disintegrin and metalloproteinase 17/tumor necrosis factor-alpha converting enzyme increases the malignant potential in human pancreatic ductal adenocarcinoma.  


A disintegrin and metalloproteinase (ADAM) molecules are known for their unique potential to combine adhesion, proteolysis, and signaling. To understand the role of ADAM17/tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) in pancreatic ductal adenocarcinoma (PDAC), we investigated its expression, function, and in vitro regulation. ADAM17/TACE mRNA was expressed in 3 of 10 normal pancreatic tissues, 6 of 8 samples from patients with chronic pancreatitis, 10 of 10 PDAC tissues, and 9 of 9 pancreatic cancer cell lines, but it was absent in primary duct epithelial cells. Immunohistochemical staining revealed positive cancer cells in 8 of 10 PDACs but no staining of ducts in normal pancreas. ADAM17/TACE was found in 0 of 16 pancreatic intraepithelial neoplasia (PanIN)-1A lesions, 1 of 30 PanIN-1B lesions, 2 of 13 PanIN-2 lesions but, in 13 of 15 PanIN-3 lesions, associated with PDAC. Western blot, flow cytometry, and confocal microscopy analyses showed the aberrant expression of ADAM17/TACE protein in pancreatic cancer cell lines. The proteolytic activity of ADAM17/TACE, assessed by the release of TNF-alpha, was inhibited by TNF-alpha protease inhibitor. ADAM17/TACE gene silencing using small interfering RNA technique in vitro reduced invasion behavior dramatically, whereas proliferation was unaffected. Furthermore, ADAM17/TACE mRNA expression was down-regulated in pancreatic cancer cells arrested in G2-M phase as well as in a time-dependent manner after TNF-alpha and interleukin-6 incubation. In conclusion, our findings provide evidence of aberrant expression of the proteolytically active ADAM17/TACE in advanced precursor lesions (PanIN-3) and PDAC while identifying its critical involvement in the invasion process. PMID:16982746

Ringel, Jörg; Jesnowski, Ralf; Moniaux, Nicolas; Lüttges, Jutta; Ringel, Jens; Choudhury, Amit; Batra, Surinder K; Klöppel, Günter; Löhr, Matthias



The glucose-lowering potential of exendin-4 orally delivered via a pH-sensitive nanoparticle vehicle and effects on subsequent insulin secretion in vivo  

Microsoft Academic Search

Exendin-4 is a potent insulinotropic agent in diabetes patients; however, its therapeutic utility is limited due to the frequent injections required. In this study, an orally available exendin-4 formulation, using an enteric-coated capsule containing pH-responsive NPs, was developed. Following oral administration of 123I-labeled-exendin-4 loaded NPs in rats, the biodistribution of the administered drug was investigated using a dual isotope dynamic

Ho-Ngoc Nguyen; Shiaw-Pyng Wey; Jyuhn-Huarng Juang; Kiran Sonaje; Yi-Cheng Ho; Er-Yuan Chuang; Chia-Wei Hsu; Tzu-Chen Yen; Kun-Ju Lin; Hsing-Wen Sung



Oral Progestogen Combined with Testosterone as a Potential Male Contraceptive: Additive Effects between Desogestrel and Testosterone Enanthate in Suppression of Spermatogenesis, Pituitary-Testicular Axis, and Lipid Metabolism  

Microsoft Academic Search

The effects of a synthetic oral progestogen, desogestrel (DSG), administered with low dose testosterone (T) were investigated to determine the optimal combination for suppression of gonadotropins and spermatogenesis to targets compatible with effective male con- traception. Twenty-four healthy male volunteers (33.2 6 0.9 yr) were randomly assigned to 3 groups (n 5 8) to receive: 1) 300 mg DSG orally



Impact of VEGF-C Gene Polymorphisms and Environmental Factors on Oral Cancer Susceptibility in Taiwan  

PubMed Central

Background Oral cancer, which is the fourth most common male cancer, is associated with environmental carcinogens in Taiwan. Vascular endothelial growth factor (VEGF)-C, an angiogenic/lymphangiogenic factor with high expression levels in tumor tissues, plays important roles in the development of several malignancies. This study was designed to examine associations of five VEGF-C gene polymorphisms with the susceptibility to and clinicopathological characteristics of oral squamous cell carcinoma. Methodology/Principal Findings Five single-nucleotide polymorphisms (SNPs) of VEGF-C were analyzed by a real-time polymerase chain reaction (PCR) in 470 male patients with oral cancer and 426 cancer-free controls. In this study, we found that the VEGF-C rs7664413 and rs2046463 polymorphisms were associated with oral-cancer susceptibility but not with any clinicopathological parameters. The GGACA or GACTG haplotype of five VEGF-C SNPs (rs3775194, rs11947611, rs1485766, rs7664413, and rs2046463) combined was also related to the risk of oral cancer. Among 611 male smokers, VEGF-C polymorphism carriers who also chewed betel quid were found to have a 14.5–24.2-fold risk of having oral cancer compared to the VEGF-C wild-type carrier who did not chew betel quid. Among 461 male betel-quid chewers, VEGF-C polymorphism carriers who also smoked had a 2.7–18.1-fold risk of having oral cancer compared to those who carried the wild type but did not smoke. Conclusions Our results suggest that the two SNPs of VEGF-C (rs7664413 and rs2046463) and either of two haplotypes of five SNPs combined have potential predictive significance in oral carcinogenesis. Gene-environmental interactions among VEGF-C polymorphisms, smoking, and betel-quid chewing might alter one's susceptibility to oral cancer.

Chien, Ming-Hsien; Liu, Yu-Fan; Hsin, Chung-Han; Lin, Chien-Huang; Shih, Chun-Han; Yang, Shun-Fa; Cheng, Chao-Wen; Lin, Chiao-Wen



[Chemotherapy for malignant gliomas: an update].  


Gliomas account for approximately 30% of all brain tumors and are thus the most common primary tumors of the central nervous system(CNS). Despite treatment with aggressive surgical resection, chemotherapy, and radiotherapy, high-grade (WHO grades III and IV)malignant gliomas, especially glioblastoma(GBM), the most common glioma in adults, kill patients within a median time span of a year after diagnosis. In Japan, alkylating agents such as 1-(4-amino-2-methyl-5-pyridiminyl)methyl-3-(2-chloroethyl)-3-nitrosourea(ACNU) and methyl-6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside(MCNU)have been used to treat malignant gliomas for a long time; however, this treatment provides few clinical benefits. Temozolomide(TMZ), an oral alkylating agent, has been demonstrated to possess antitumor activity against malignant gliomas with minimal additional toxicity; furthermore, a previous study found that treatment with TMZ significantly prolonged median survival time. In 2006, TMZ was certified as the treatment agent for malignant gliomas by the National Ministry of Health and Welfare of Japan. It is now used as first-line therapy. However, its clinical outcomes depend on the O6 -methylguanine- DNA methyltransferase(MGMT)status, and MGMT modification is one of the key factors to deriving greater clinical benefits in the future. Combination therapy with TMZ and other antitumor drugs, especially anti-vascular endothelial growth factor(VEGF) antibody(Avascin), has been aggressively investigated for treating gliomas. Some of these drugs have been studied in experimental animal models and advanced to clinical trials. These studies suggest that combination therapy with TMZ and other antitumor drugs might further improve the clinical outcome of malignant gliomas as compared to TMZ plus radiotherapy. Based on these data, the next step will be to carry out phase II to III clinical studies to improve treatment of malignant brain tumors further. PMID:24105052

Wakabayashi, Toshihiko; Natsume, Atsushi; Fujii, Masazumi



Targeting hedgehog in hematologic malignancy.  


The Hedgehog pathway is a critical mediator of embryonic patterning and organ development, including hematopoiesis. It influences stem cell fate, differentiation, proliferation, and apoptosis in responsive tissues. In adult organisms, hedgehog pathway activity is required for aspects of tissue maintenance and regeneration; however, there is increasing awareness that abnormal hedgehog signaling is associated with malignancy. Hedgehog signaling is critical for early hematopoietic development, but there is controversy over its role in normal hematopoiesis in adult organisms where it may be dispensable. Conversely, hedgehog signaling appears to be an important survival and proliferation signal for a spectrum of hematologic malignancies. Furthermore, hedgehog signaling may be critical for the maintenance and expansion of leukemic stem cells and therefore provides a possible mechanism to selectively target these primitive cell subpopulations, which are resistant to conventional chemotherapy. Indeed, phase 1 clinical trials of hedgehog pathway inhibitors are currently underway to test this hypothesis in myeloid leukemias. This review covers: (1) the hedgehog pathway and its role in normal and malignant hematopoiesis, (2) the recent development of clinical grade small molecule inhibitors of the pathway, and (3) the potential utility of hedgehog pathway inhibition as a therapeutic strategy in hemato-oncology. PMID:22223823

Irvine, David A; Copland, Mhairi



Gabapentin in the Treatment of Persistent Hiccups in Advanced Malignancy  

PubMed Central

Hiccups are a distressing symptom in advanced malignancies in the setting of palliative care. A case of persistent hiccups treated with oral Gabapentin is presented to highlight the clinical and ethical dilemmas in patients with advanced malignancy. A 70-year-old male with non-small cell cancer of the lung with widespread metastases presented with persistent hiccups. The patient and family sought only symptom relief from home, without hospitalization or further investigations. The hiccups were dramatically relieved by oral Gabapentin, highlighting the recent reports that mention this molecule as being useful for hiccups. Gabapentin is a simple tool that may be utilized by palliative care physicians to relieve hiccups in advanced malignancies.

Menon, Mahesh



Malignancies in Down Syndrome  

Microsoft Academic Search

Down Syndrome (DS) is associated with an increased incidence of malignancies, especially leukaemias. We came across 8 DS children\\u000a presenting with malignancies and having trisomy 21 as the sole cytogenetic abnormality. Of these 8 DS cases, 4 presented with\\u000a acute lymphocytic leukaemia, 2 with acute myeloid leukaemia and one case each with Hodgkin’s disease and Wilms’ tumour. There\\u000a are contradictory

P. Kusumakumary; T. S. Vats; Ravindran Ankathil; H. Rao Gattamaneni; M. Krishnan Nair



Malignant hypertonic hyperpyrexia syndrome  

Microsoft Academic Search

Summary  Two cases of a malignant hypertonic cyanotic hyperpyrexic syndrome which terminated in death are presented. Succinylcholine\\u000a is suggested as the trigger mechanism in each case. Common diagnostic features were: (1) hypertonia, including (a) jaw stiffness\\u000a and (b) subsequent intensive generalized muscle spasm; (2) cyanosis with an accompanying myoglobinuria; (3) malignant hyper-pyrexia;\\u000a and (4) hyperkalaemia. Abnormal jaw stiffness was evident following

James A. Gibson; Douglas M. Gardiner



Malignant Glioma: Chemotherapy Perspective  

Microsoft Academic Search

\\u000a Despite optimal surgery and adjuvant radiotherapy, malignant gliomas almost always recur. One cause of failure is explained\\u000a by the diffusely infiltrating pattern of growth displayed by most gliomas, with malignant cells disseminated far beyond the\\u000a initial bulky tumor. Although most relapses occur at or near the initial site of tumor, either along the resection margin\\u000a or at the edge of

Roger Stupp; J. Gregory Cairncross


Sorafenib Tosylate in Treating Patients With Malignant Mesothelioma.

Epithelial Mesothelioma; Recurrent Malignant Mesothelioma; Sarcomatous Mesothelioma; Stage IA Malignant Mesothelioma; Stage IB Malignant Mesothelioma; Stage II Malignant Mesothelioma; Stage III Malignant Mesothelioma; Stage IV Malignant Mesothelioma



Oral bisphosphonate associated osteonecrosis of the jaws: three case reports  

Microsoft Academic Search

Bisphosphonate associated osteonecrosis of the jaws (BONJ) has been well documented recently in relation to intravenous preparations of the drug. These are most commonly used as part of the management of hypercalcaemia of malignancy and metastatic bone disease but BONJ can also occur in association with oral bisphosphonate use. The oral preparations can also be prescribed in the management of

A. Y. Pai; N. J. Malden



Zolmitriptan Oral  


... with other symptoms such as upset stomach and sensitivity to sound and light). Zolmitriptan is in a ... To take the orally disintegrating tablet, use dry hands to peel back the foil packaging. Immediately take ...


Oral Thrush  


... sugar, which encourages the growth of candida. Vaginal yeast infections. Vaginal yeast infections are caused by the same fungus that causes oral thrush. Although a yeast infection isn't dangerous, if you're pregnant ...


Oral pemphigoid  

Microsoft Academic Search

Objective. Cicatricial pemphigoid (CP) is an autoimmune blistering disease characterized by anti-basement membrane zone (BMZ) antibodies with a varied heterogeneous clinical spectrum. We sought to characterize a subset of patients with disease limited to the oral cavity.Study Design. Twenty-nine random patients with vesiculobullous disease limited to the oral cavity were studied. We identified patients by clinical criteria, the presence of

Narciss Mobini; Neville Nagarwalla; A. Razzaque Ahmed



Primary Malignant Rhabdoid Melanoma  

PubMed Central

Melanoma with rhabdoid features is an uncommon variant of malignant melanoma. Here, we describe a rare case of primary rhabdoid malignant melanoma. A 54-year-old man presented with a black tumor measuring 3×4 cm on the right forearm. Histologic sections showed a tumor mass with rhabdoid features composed entirely of polygonal neoplastic cells with eccentric nuclei, prominent nucleoli, and large hyaline cytoplasmic inclusions. The tumor cells were immunoreactive with HMB-45, S100, Fontana-Masson silver and vimentin, and negative for smooth muscle actin, CD68, CD34, CD99, synaptophysin, desmin, and PAS. The differential diagnosis for this tumor included malignant peripheral nerve sheath tumor, malignant peripheral neuroectodermal tumor and rhabdomyosarcoma. The patient was treated with a wide excision and a local skin graft. The excised tumor was entirely composed of rhabdoid tumor cells. No recurrence or metastasis was evident 4 months after removal. This article is relevant to rare cases of primary malignant melanomas showing rhabdoid tumor cells over the entire excised lesion.

Chung, Bo Young; Ahn, In Su; Cho, Soo Ick; Kim, Hye One; Kim, Kwang Ho; Park, Chun Wook



Endothelin receptor type B gene promoter hypermethylation in salivary rinses independently associates with risk of oral cavity cancer and premalignancy  

PubMed Central

Endothelin receptor type B (EDNRB) and kinesin family member 1A(KIF1A) are candidate tumor suppressor genes that are inactivated in cancers. In this study we evaluated promoter hypermethylation of EDNRB and KIF1A and their potential use for risk classification in prospectively collected salivary rinses from patients with premalignant/malignant oral cavity lesions. Quantitative methylation-specific PCR(Q-MSP) was performed analyzing methylation status of EDNRB and KIF1A in salivary rinses of 191 patients. We proceeded to determine the association of methylation status with histologic diagnosis and estimate classification accuracy. On univariate analysis, diagnosis of dysplasia/cancer was associated with age and KIF1A or EDNRB methylation. Methylation of EDNRB highly correlated with that of KIF1A(p<0.0001). On multivariable modeling, histologic diagnosis independently associated with EDNRB(p=0.0003) or KIF1A(p=0.027) methylation). A subset of patients analyzed (n=161) without prior biopsy proven malignancy received clinical risk classification based on examination. On univariate analysis, EDNRB and risk classification were associated with diagnosis of dysplasia/cancer, and remained significant on multivariate analysis (EDNRB:p=0.047, risk classification:p=0.008). Clinical risk classification identified dysplasia/cancer with a sensitivity of 71% and specificity of 58%. The sensitivity of clinical risk classification combined with EDNRB methylation improved to 75%. EDNRB methylation in salivary rinses was independently associated with histologic diagnosis of premalignancy and malignancy and may have potential in classifying patients at risk for oral premalignant and malignant lesions in settings without access to a skilled dental practitioner. This may also potentially identify patients with premalignant and malignant lesions that do not meet criteria for high clinical risk based on skilled dental examination.

Pattani, Kavita Malhotra; Zhang, Zhe; Demokan, Semra; Glazer, Chad; Loyo, Myriam; Goodman, Steven; Sidransky, David; Bermudez, Francisco; Jean-Charles, Germain; McCaffrey, Thomas; Padhya, Tapan; Phelan, Joan; Spivakovsky, Silvia; Bowne, Helen Yoo; Goldberg, Judith D.; Rolnitzky, Linda; Robbins, Miriam; Kerr, A. Ross; Sirois, David; Califano, Joseph A.



Support vector machines for oral lesion classification  

Microsoft Academic Search

We investigate support vector machines (SVM) in the context of oral lesion classification using digital color images as input. Two common lesions of similar visual appearance to the human observer were evaluated: oral leukoplakia, which is a potentially pre-cancerous lesion, and oral lichenoid reactions (with subclasses of atrophic, plaqueformed and reticular reactions), which are usually harmless lesions. In total, 89%

Artur Chodorowski; Tomas Gustavsson; Ulf Mattsson



Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise  

PubMed Central

There is much interest in the potential use of Cox-2 selective inhibitors in combination with other cancer therapeutics. Malignancies of hematopoietic and non-hematopoietic origin often have increased expression of cyclooxygenase-2 (Cox-2), a key modulator of inflammation. For example, hematological malignancies such as chronic lymphocytic leukemia, chronic myeloid leukemia, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma and multiple myeloma often highly express Cox-2, which correlates with poor patient prognosis. Expression of Cox-2 enhances survival and proliferation of malignant cells, while negatively influencing anti-tumor immunity. Hematological malignancies expressing elevated levels of Cox-2 potentially avoid immune responses by producing factors that enhance angiogenesis and metastases. Cellular immune responses regulated by natural killer cells, cytotoxic T lymphocytes, and T regulatory cells are also influenced by Cox-2 expression. Therefore, Cox-2 selective inhibitors have promising therapeutic potential in patients suffering from certain hematological malignancies.

Bernard, M. P.; Bancos, S.; Sime, P. J.; Phipps, R. P.



Feasibility of using gold nanorods for optical contrast in two photon microscopy of oral carcinogenesis  

NASA Astrophysics Data System (ADS)

Gold nanorods (GNRs) combined with two-photon microscopy were explored for potential application in imaging of oral carcinogenesis. GNRs have been shown to be effective contrast agents for two photon luminescence in that excitation laser powers required for imaging are low compared to traditional fluorophores. Imaging of cells, ex vivo tissues, and in vivo oral mucosa labeled with GNRs was performed to evaluate potential advantages of these agents in molecular imaging of epithelial carcinogenesis. Powers required to elicit a two-photon luminescence signal from GNRs were determined for cells as well as normal and malignant transformed lesions, 24 hours following injection of GNRs in a hamster model for oral cancer. The strength of the detected emission as the function of the average incident laser power was measured in tissues with and without GNRs to compare the sensitivity of GNRs against tissue autofluorescence. Finally, in vivo imaging was performed immediately following GNR injection to establish the ability to image microvasculature at low incident powers. The pilot study demonstrated uptake of GNRs by cells and in tissues yielding bright fluorescence signals using significantly lower incident powers than those needed to excite tissue autofluorescence. The in vivo imaging aspect of the study demonstrated the localization of GNRs within the microvasculature of the oral cancer model. These preliminary studies demonstrated the ability of GNRs to function as photostable, high contrast imaging agents and suggest that GNRs and multi-photon imaging have great potential for applications in the field of molecular imaging and early detection of cancer.

Motamedi, Saam; Shilagard, Tuya; Koong, Luke; Vargas, Gracie



Cancer stem cells and human malignant melanoma  

PubMed Central

Summary Cancer stem cells (CSC) have been identified in hematological malignancies and several solid cancers. Similar to physiological stem cells, CSC are capable of self-renewal and differentiation and have the potential for indefinite proliferation, a function through which they may cause tumor growth. Although conventional anti-cancer treatments might eradicate most malignant cells in a tumor, they are potentially ineffective against chemoresistant CSC, which may ultimately be responsible for recurrence and progression. Human malignant melanoma is a highly aggressive and drug-resistant cancer. Detection of tumor heterogeneity, undifferentiated molecular signatures, and increased tumorigenicity of melanoma subsets with embryonic-like differentiation plasticity strongly suggest the presence and involvement of malignant melanoma stem cells (MMSC) in the initiation and propagation of this malignancy. Here, we review these findings in the context of functional properties ascribed to melanocyte stem cells and CSC in other cancers. We discuss the association of deregulated signaling pathways, genomic instability, and vasculogenic mimicry phenomena observed in melanoma subpopulations in light of the CSC concept. We propose that a subset of MMSC may be responsible for melanoma therapy-resistance, tumor invasiveness, and neoplastic progression and that targeted abrogation of a MMSC compartment could therefore ultimately lead to stable remissions and perhaps cures of metastatic melanoma.

Schatton, Tobias; Frank, Markus H



Cancer stem cells and human malignant melanoma.  


Cancer stem cells (CSC) have been identified in hematological malignancies and several solid cancers. Similar to physiological stem cells, CSC are capable of self-renewal and differentiation and have the potential for indefinite proliferation, a function through which they may cause tumor growth. Although conventional anti-cancer treatments might eradicate most malignant cells in a tumor, they are potentially ineffective against chemoresistant CSC, which may ultimately be responsible for recurrence and progression. Human malignant melanoma is a highly aggressive and drug-resistant cancer. Detection of tumor heterogeneity, undifferentiated molecular signatures, and increased tumorigenicity of melanoma subsets with embryonic-like differentiation plasticity strongly suggest the presence and involvement of malignant melanoma stem cells (MMSC) in the initiation and propagation of this malignancy. Here, we review these findings in the context of functional properties ascribed to melanocyte stem cells and CSC in other cancers. We discuss the association of deregulated signaling pathways, genomic instability, and vasculogenic mimicry phenomena observed in melanoma subpopulations in light of the CSC concept. We propose that a subset of MMSC may be responsible for melanoma therapy-resistance, tumor invasiveness, and neoplastic progression and that targeted abrogation of a MMSC compartment could therefore ultimately lead to stable remissions and perhaps cures of metastatic melanoma. PMID:18353142

Schatton, Tobias; Frank, Markus H



Malignant pleural disease.  


The vast majority of pleural neoplasms invade the pleura secondarily and can be seen in patients with bronchogenic carcinoma, breast cancer, lymphoma, and ovarian or gastric carcinoma. Primary pleural neoplasms are less common, although they have developed notoriety since the up-surge of malignant mesothelioma and the knowledge of its connection to asbestos exposure. Other malignant primary tumors include localized fibrous tumor and pleural liposarcoma. In most patients with diffuse malignant pleural disease the chest radiograph shows pleural effusion with or without pleural thickening. Computed tomography (CT) usually provides precise localization and extent of the disease and may be of value in assessing chest wall and mediastinal involvement. In specific situations, magnetic resonance (MR) may be useful as a problem-solving tool when CT findings of chest wall or diaphragmatic invasion are equivocal or in patients with contraindication to intravenous administration of ionic contrast material. PMID:10874176

Bonomo, L; Feragalli, B; Sacco, R; Merlino, B; Storto, M L



Inhibition of osteosarcoma-induced thermal hyperalgesia in mice by the orally active dual enkephalinase inhibitor PL37. Potentiation by gabapentin  

Microsoft Academic Search

We have previously shown that stimulation of peripheral opioid receptors by exogenous opiates counteracts the thermal hyperalgesia elicited by a tibial osteosarcoma due to intraosteal inoculation of NCTC 2472 cells to mice. Aiming to study whether pheripheral endogenous enkephalins could also counteract this painful symptom, we assayed in this model the effects of PL37, an orally active dual inhibitor of

Luis Menéndez; Agustín Hidalgo; Álvaro Meana; Hervé Poras; Marie-Claude Fournié-Zaluski; Bernard P. Roques; Ana Baamonde



Topical Review: Neuroleptic Malignant Syndrome in Children and Adolescents  

Microsoft Academic Search

Neuroleptic malignant syndrome is a rare but potentially fatal complication of treatment with antipsychotic medications. Prior to 1994, there was no accepted set of diagnostic criteria. This article presents four adolescents admitted at Cleveland Clinic Foundation from 1985 to 1998, illustrating the broad spectrum of neuroleptic malignant syndrome. A review of the pediatric literature is discussed as to the current

Edna B. Ty; A. David Rothner



Malignant Hyperpyrexia during Anaesthesia: Possible Association with Subclinical Myopathy  

Microsoft Academic Search

The members of a family in whom three malignant hyperpyrexial deaths occurred during anaesthesia were studied by means of serum creatine phosphokinase estimations. Abnormally high levels were found in many asymptomatic relatives. It is suggested that the abnormal levels reflect a subclinical myopathy of autosomal dominant inheritance which possesses a potentially lethal propensity resulting in a malignant hyperpyrexia when challenged

H. Isaacs; M. B. Barlow



Surveillance for gastrointestinal malignancies  

PubMed Central

Gastrointestinal (GI) malignancies are notorious for frequently progressing to advanced stages even in the absence of serious symptoms, thus leading to delayed diagnoses and dismal prognoses. Secondary prevention of GI malignancies through early detection and treatment of cancer-precursor/premalignant lesions, therefore, is recognized as an effective cancer prevention strategy. In order to efficiently detect these lesions, systemic application of screening tests (surveillance) is needed. However, most of the currently used non-invasive screening tests for GI malignancies (for example, serum markers such as alpha-fetoprotein for hepatocellular carcinoma, and fecal occult blood test, for colon cancer) are only modestly effective necessitating the use of highly invasive endoscopy-based procedures, such as esophagogastroduodenoscopy and colonoscopy for screening purposes. Even for hepatocellular carcinoma where non-invasive imaging (ultrasonography) has become a standard screening tool, the need for repeated liver biopsies of suspicious liver nodules for histopathological confirmation can’t be avoided. The invasive nature and high-cost associated with these screening tools hinders implementation of GI cancer screening programs. Moreover, only a small fraction of general population is truly predisposed to developing GI malignancies, and indeed needs surveillance. To spare the average-risk individuals from superfluous invasive procedures and achieve an economically viable model of cancer prevention, it’s important to identify cohorts in general population that are at substantially high risk of developing GI malignancies (risk-stratification), and select suitable screening tests for surveillance in these cohorts. We herein provide a brief overview of such high-risk cohorts for different GI malignancies, and the screening strategies that have commonly been employed for surveillance purpose in them.

Tiwari, Ashish K; Laird-Fick, Heather S; Wali, Ramesh K; Roy, Hemant K



Oral cysticercosis: a clinical dilemma.  


Cysticercosis is a potentially fatal parasitic disease caused by cysticercus cellulosae, the larval stage of Taenia solium. Oral cysticercosis is a rare entity and represents difficulty in clinical diagnosis. This article reports two cases of oral cysticercosis involving buccal and labial mucosa. Both the cases presented with solitary, nodular swelling that had been clinically diagnosed as a mucocele. Histopathology of excisional biopsy revealed it to be cysticercosis. Single, cystic nodular swelling of oral cavity may be the only evidence of cysticercosis and may present first to dentist. These cases emphasise the role of dentist and thorough histopathological examination in the early diagnosis of disease that can prevent potential systemic complication. PMID:23580668

Wanjari, Sangeeta Panjab; Patidar, Kalpana A; Parwani, Rajkumar N; Tekade, Satyajitraje A



Immunotherapy of Genitourinary Malignancies  

PubMed Central

Most cancer patients are treated with some combination of surgery, radiation, and chemotherapy. Despite recent advances in local therapy with curative intent, chemotherapeutic treatments for metastatic disease often remain unsatisfying due to severe side effects and incomplete long-term remission. Therefore, the evaluation of novel therapeutic options is of great interest. Conventional, along with newer treatment strategies target the immune system that suppresses genitourinary (GU) malignancies. Metastatic renal cell carcinoma and non-muscle-invasive bladder caner represent the most immune-responsive types of all human cancer. This review examines the rationale and emerging evidence supporting the anticancer activity of immunotherapy, against GU malignancies.

Inamoto, Teruo; Azuma, Haruhito



Desmoplastic malignant mesothelioma.  


Desmoplastic mesothelioma is a rare subtype of diffuse malignant mesothelioma. A 72-year-old woman from East Anatolia presented with chest pain. The images of body positron emission tomography revealed irregular, left pleural thickening involving mediastinal and diaphragmatic surfaces with hypermetabolic characterization. The diagnosis of desmoplastic malignant mesothelioma was confirmed by minithoracotomy and immunohistochemical staining with pan-cytokeratin, cytokeratin 5/6, calretinin, carcinoembryonic antigen, thyroid transcription factor-1, CD15, and HMB-45 on the biopsy specimen. This case is unique in terms of the reporting patient being from a nonendemic area for asbestos-related diseases and in terms of its rare histopathology. PMID:23609252

Baççio?lu, Ay?e; Kaba, Erkan; Ozmen, Sevilay A; Demirci, Munir



Umbilical Complications of Malignancy  

Microsoft Academic Search

Introduction  Cancer patients may manifest a variety of intraabdominal complications occurring during various phases of their illness; however,\\u000a little in the literature exists regarding umbilical abnormalities in this population.\\u000a \\u000a \\u000a \\u000a Discussion  Umbilical metastases (Sister Mary Joseph’s sign) are the most common malignant complication involving the umbilicus and may\\u000a be the presenting manifestation of visceral malignancy. Cancer patients may occasionally experience periumbilical ecchymosis\\u000a (Cullen’s

Mark A. Marinella



Malignant thymoma: current status and future directions  

Microsoft Academic Search

Malignant thymomas are rare indolent tumours of the anterior superior mediastinum. Despite a benign histologic appearance, some thymomas invade nearby structures or metastasize. Patients are commonly asymptomatic, but some may present with unusual paraneoplastic syndromes such as myasthenia gravis, pure red cell aplasia, or hypogammaglobulinemia. Since tumour biopsy may potentially disrupt the thymic capsule, it is often not performed. Patients



Kaposi sarcoma-associated herpesvirus (KSHV) induces a functional tumor-associated phenotype for oral fibroblasts  

PubMed Central

The Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), the most common HIV/AIDS-associated tumor worldwide. Involvement of the oral cavity portends a poor prognosis for patients with KS, but mechanisms for KSHV regulation of the oral tumor microenvironment are largely unknown. Infiltrating fibroblasts are found with KS lesions, and KSHV establishes latent infection within human primary fibroblasts in vitro, but contributions for KSHV-infected fibroblasts to the KS microenvironment have not been previously characterized. Secretion of pro-migratory factors and intratumoral invasion are characteristics of tumor-associated fibroblasts (TAF) found in the microenvironment of non-viral malignancies. In the present study, we show that latent KSHV infection of primary human fibroblasts isolated from the oral cavity enhances their secretion of KS-promoting cytokines and intrinsic invasiveness through VEGF-dependent mechanisms. Moreover, we find that KSHV induces these effects through Sp1- and Egr2-dependent transcriptional activation of the extracellular matrix metalloproteinase inducer (emmprin). These data implicate KSHV activation of emmprin in the induction of a “TAF-like” phenotype for oral fibroblasts in the KS microenvironment and support the potential utility of targeting TAFs and/or emmprin in the treatment of oral KS.

Dai, Lu; Qin, Zhiqiang; Defee, Michael; Toole, Bryan; Kirkwood, Keith L.; Parsons, Chris



Oral myiasis  

PubMed Central

Myiasis is a relatively rare condition arising from the invasion of body tissues or cavities of living animals or humans by maggots or larvae of certain species of flies. It is an uncommon clinical condition, being more frequent in underdeveloped countries and hot climate regions, and is associated with poor hygiene, suppurative oral lesions; alcoholism and senility. Its diagnosis is made basically by the presence of larvae. The present article reports a case of oral myiasis involving 20 larvae in a patient with neurological deficiency.

Pereira, Treville; Tamgadge, Avinash P.; Chande, Mayura S.; Bhalerao, Sudhir; Tamgadge, Sandhya



Chemotherapy and targeted agents for thymic malignancies.  


Thymic malignancies are rare epithelial tumors that may be aggressive and difficult to treat. Thymomas are usually localized to the anterior mediastinum and are frequently eligible for upfront surgical resection. However, nearly 30% of patients present with locally advanced tumors at time of diagnosis, and chemotherapy is then used to reduce the tumor burden, possibly allowing subsequent surgery and/or radiotherapy. Metastatic and recurrent thymic malignancies may similarly be treated with chemotherapy. More recently, the molecular characterization of thymoma and thymic carcinoma led to the identification of potentially druggable targets, laying the foundations to implement personalized medicine for patients. PMID:22594902

Girard, Nicolas



Cytokeratin positive T cell malignant lymphoma.  

PubMed Central

A high grade T cell malignant lymphoma is described in which weak staining of tumour cells for leucocyte common antigen and T cell markers coexisted with strong positive cytoplasmic staining with the anticytokeratin marker CAM 5.2. This is the first report of non-CD30 positive T cell lymphoma showing cytokeratin positivity. On ultrastructural examination there was no evidence of epithelial differentiation or of accumulation of cytokeratin-type intermediate filaments. The case adds to the range of malignant lymphomas which can, on rare occasions, show cytokeratin positivity. Pathologists should be aware of this potential diagnostic pitfall if inappropriate investigations and therapeutic regimens are to be avoided. Images

McCluggage, W G; el-Agnaff, M; O'Hara, M D



Malignant adnexal neoplasms  

Microsoft Academic Search

Malignant cutaneous adnexal neoplasms are one of the most challenging areas of dermatopathology. Tumors of the pilosebaceous apparatus can occur as single-lineage neoplasms or may manifest as complex proliferations with multilineal differentiation patterns including not only the germinative component of the hair bulb, the inner or outer root sheath epithelium and the sebaceous gland and duct, but also the sweat

A Neil Crowson; Cynthia M Magro; Martin C Mihm



Postirradiation malignant fibrous histiocytoma  

SciTech Connect

Three patients who were treated successfully with postoperative external radiation therapy for ovarian carcinoma, endometrial adenocarcinoma, and bilateral retinoblastoma respectively developed years later malignant fibrous histiocytoma (MFH) within the irradiated field. MFH is a recently described soft tissue sarcoma known for its dual fibroblastic and histiocytic differentiation resulting in a pleomorphic histologic appearance.

Tewfik, H.H.; Tewfik, F.A.; Latourette, H.B.



Liver Transplantation for Malignancy  

Microsoft Academic Search

Liver transplantation for hepatic malignancies has emerged from an exotic and desperate approach to a well- documented and proven treatment modality for these unfortunate patients. However, early unsatisfactory results emphasized that only a highly selected patient population would benefit from transplantation. Currently, <10% of all liver transplants performed are for hepatocellular cancer (HCC). There is no controversy that hepatoblastoma is



Malignant tumors of childhood  

SciTech Connect

This book contains 34 papers about malignant tumors. some of the titles are: Invasive Cogenital Mesoblastic Nephroma, Leukemia Update, Unusual Perinatal Neoplasms, Lymphoma Update, Gonadal Germ Cell Tumors in Children, Nutritional Status and Cancer of Childhood, and Chemotherapy of Brain tumors in Children.

Brooks, B.J.



Neuroleptic malignant syndrome  

Microsoft Academic Search

Sirs: We report a patient who developed neuroleptic malignant syndrome (NMS) and elevated serum amylase and lipase levels. A 50-year-old man was admitted because of a 2-week history of unsteady gait, generalized tremor and altered consciousness. Two years earlier, the patient had begun treatment with twice daily doses of trihexyphenidyl Hcl 4 mg and haloperidol decanoate 50 mg once monthly

Tsong-Hai Lee; Lok-Ming Tang



Efficacy of palifermin (keratinocyte growth factor-1) in the amelioration of oral mucositis  

PubMed Central

Purpose: Oral mucositis is a significant toxicity of cytotoxic chemo- and radiation-therapy used to treat cancer. Palifermin is the first pharmaceutical/biological agent approved for the intervention of oral mucositis. The major objective of this review is to evaluate the evidence supporting the use of palifermin. Methods: A literature search was performed using an appropriate keyword search in MEDLINE and PubMed databases. Results: Of 100 full papers and 4 abstracts identified, 12 papers and 3 abstracts were appropriate for analysis. Level 2 evidence supporting palifermin use in patients with hematologic malignancies being treated with autologous hematopoietic stem cell transplantation (HSCT) is clear. Level 2 evidence also exists for the use of palifermin in the prevention of oral mucositis in patients with solid tumors (colorectal cancer, head and neck cancer), but is incomplete. Level ? 3 data support the use of palifermin in allogeneic HSCT recipients and cycled chemotherapy. A single health economic study concluded that palifermin is essentially cost neutral in the autologous HSCT population. Conclusion: Data supporting the use of palifermin in autologous HSCT recipients with hematologic malignancies is clear. Some data exist demonstrating its efficacy in other oncologic indications. Additional studies are needed to broaden the potential applications of palifermin and to ascertain its economic, but not symptomatic, effectiveness.

Sonis, Stephen T



Malignant Hyperthermia During Laparoscopic Adjustable Gastric Banding  

PubMed Central

Background: We report a rare case of malignant hyperthermia during laparoscopic adjustable gastric banding. Case Description: A 32-y-old female with no previous history of adverse reaction to general anesthesia underwent laparoscopic adjustable gastric banding. Intraoperative monitoring revealed a sharp increase in end-tidal carbon dioxide, autonomic instability, and metabolic and respiratory acidosis, along with other metabolic and biochemical derangements. She was diagnosed with malignant hyperthermia. Desflurane, the anesthetic agent was discontinued, and the patient was started on intravenous dantrolene. Results: The surgery was completed, and the patient was brought to the surgical intensive care unit for continued postoperative care. She developed muscle weakness and phlebitis that resolved prior to discharge. Conclusion: Prompt diagnosis and treatment of malignant hyperthermia leads to favorable clinical outcome. This clinical entity can occur in the bariatric population with the widely used desflurane. Bariatric surgeons and anesthesiologists alike must be aware of the early clinical signs of this rare, yet potentially fatal, complication.

Chery, Josue; Shintaro, Chiba; Pratt, Ambibola; Kirkley, Ronell; Hearne, Barbara; Beyzman, Andrew



An uncommon malignant cutaneous squamomelanocytic tumor  

PubMed Central

The intermingling of two malignant neoplasms within the same cutaneous tumor is rare. No consensus has been reached for a clear definition and categorization. In the current study, we describe a cutaneous neoplasm; a squamomelanocytic tumor (SMT) with histological features combining those of a squamous cell carcinoma (SCC) and a malignant melanoma (MM). This is the second report of an oculocutaneous SMT, and concerns a subject with a 20-year history of solar lentigo coexisting with solar keratosis in the primary lesion. This type of tumor is quite rare, with a distinct cytological architecture and immunohistochemical features, and the differential diagnosis of SMT may be considered. However, the histogenesis, biological behavior and malignant potential of SMTs remain a matter of speculation. With regard to the treatment, complete surgical resection and close follow-up are recommended.




Hydrocortisone Oral  


... will decrease your dose gradually to allow your body to adjust before stopping the drug completely. Watch for these side effects if you are gradually decreasing your dose and after you stop taking the tablets or oral liquid, even if you switch to an inhalation. If ...


Triamcinolone Oral  


... will decrease your dose gradually to allow your body to adjust before stopping the drug completely. Watch for these side effects if you are gradually decreasing your dose and after you stop taking the tablets or oral liquid, even if you switch to an inhalation. If ...


Dexamethasone Oral  


... will decrease your dose gradually to allow your body to adjust before stopping the drug completely. Watch for these side effects if you are gradually decreasing your dose and after you stop taking the tablets or oral liquid, even if you switch to an inhalation corticosteroid ...


Oral Care  

Microsoft Academic Search

Adequate dental and oral hygiene may become a challenge for all users and especially for elderly people and young children because of their limited motor skills. The same holds true for patients undergoing\\/recovering from chemo-\\/radiotherapy with accompanying sensitive mucosal conditions. Poor dental hygiene can result in tooth decay, gingivitis, periodontitis, tooth loss, bad breath (halitosis), fungal infection and gum diseases.

Irène Hitz Lindenmüller; J. Thomas Lambrecht



Oral history  

Microsoft Academic Search

Recording memories of World War II is an intervention that can humanize geriatric care in addition to the historical significance provided. Participants in this oral history project described memories of World War II and expressed themes of patriotism, loss, tense moments, makeshift living, self-sufficiency, and uncertain journey. Their ethnic roots were primarily Scandinavian, Dutch, German, and English. The nursing home

Lois B. Taft; Mary Ellen Stolder; Alice Briolat Knutson; Karolyn Tamke; Jennifer Platt; Tara Bowlds



Oral care.  


Adequate dental and oral hygiene may become a challenge for all users and especially for elderly people and young children because of their limited motor skills. The same holds true for patients undergoing/recovering from chemo-/radiotherapy with accompanying sensitive mucosal conditions. Poor dental hygiene can result in tooth decay, gingivitis, periodontitis, tooth loss, bad breath (halitosis), fungal infection and gum diseases. The use of a toothbrush is the most important measure for oral hygiene. Toothbrushes with soft bristles operated carefully by hand or via an electric device help to remove plaque and to avoid mucosal trauma. A handlebar with a grip cover can be helpful for manually disabled patients or for those with reduced motor skills. In case of oral hygiene at the bedside or of patients during/after chemo-/radiotherapy a gauze pad can be helpful for gently cleaning the teeth, gums and tongue. The use of fluoride toothpaste is imperative for the daily oral hygiene. Detergents such as sodium lauryl sulphate improve the cleaning action but may also dehydrate and irritate the mucous membrane. The use of products containing detergents and flavouring agents (peppermint, menthol, cinnamon) should therefore be avoided by bedridden patients or those with dry mouth and sensitive mucosa. Aids for suitable interdental cleaning, such as dental floss, interdental brushes or dental sticks, are often complicated to operate. Their correct use should be instructed by healthcare professionals. To support dental care, additional fluoridation with a fluoride gel or rinse can be useful. Products further containing antiseptics such as chlorhexidine or triclosan reduce the quantity of bacteria in the mouth. For patients undergoing or having undergone radio-/chemotherapy, a mouthwash that concomitantly moisturizes the oral mucosa is advisable. PMID:21325845

Hitz Lindenmüller, Irène; Lambrecht, J Thomas



Oral tolerance  

PubMed Central

Summary The gut-associated lymphoid tissue is the largest immune organ in the body and is the primary route by which we are exposed to antigens. Tolerance induction is the default immune pathway in the gut, and the type of tolerance induced relates to the dose of antigen fed: anergy/deletion (high dose) or regulatory T-cell (Treg) induction (low dose). Conditioning of gut dendritic cells (DCs) by gut epithelial cells and the gut flora, which itself has a major influence on gut immunity, induces CD103+ retinoic acid-dependent DC that induces Tregs. A number of Tregs are induced at mucosal surfaces. Th3 type Tregs are transforming growth factor-? dependent and express latency-associated peptide (LAP) on their surface and were discovered in the context of oral tolerance. Tr1 type Tregs (interleukin-10 dependent) are induced by nasal antigen and forkhead box protein 3+ iTregs are induced by oral antigen and by oral administration of aryl hydrocarbon receptor ligands. Oral or nasal antigen ameliorates autoimmune and inflammatory diseases in animal models by inducing Tregs. Furthermore, anti-CD3 monoclonal antibody is active at mucosal surfaces and oral or nasal anti-CD3 monoclonal antibody induces LAP+ Tregs that suppresses animal models (experimental autoimmune encephalitis, type 1 and type 2 diabetes, lupus, arthritis, atherosclerosis) and is being tested in humans. Although there is a large literature on treatment of animal models by mucosal tolerance and some positive results in humans, this approach has yet to be translated to the clinic. The successful translation will require defining responsive patient populations, validating biomarkers to measure immunologic effects, and using combination therapy and immune adjuvants to enhance Treg induction. A major avenue being investigated for the treatment of autoimmunity is the induction of Tregs and mucosal tolerance represents a non-toxic, physiologic approach to reach this goal.

Weiner, Howard L.; da Cunha, Andre Pires; Quintana, Francisco; Wu, Henry



Oral Tolerance  

PubMed Central

Summary The gut-associated lymphoid tissue (GALT) is the largest immune organ in the body and is the primary route by which we are exposed to antigens. Tolerance induction is the default immune pathway in the gut, and the type of tolerance induced relates to the dose of antigen fed: anergy/deletion (high dose) or regulatory T-cell (Treg) induction (low dose). Conditioning of gut dendritic cells by gut epithelial cells and the gut flora, which itself has a major influence on gut immunity, induces a CD103+ retinoic acid-dependent dendritic cell that induces Tregs. A number of Tregs are induced at mucosal surfaces. Th3 type Tregs are transforming growth factor-? (TGF-?) dependent and express latency-associated peptide (LAP) on their surface and were discovered in the context of oral tolerance. Tr1 type Tregs (interleukin-10 dependent) are induced by nasal antigen and Foxp3 iTregs are induced by oral antigen and by oral administration of aryl hydrocarbon receptor ligands. Oral or nasal antigen ameliorates autoimmune and inflammatory diseases in animal models by inducing Tregs. Furthermore, anti-CD3 monoclonal antibody is active at mucosal surfaces and oral or nasal anti-CD3 monoclonal antibody induces a LAP+ Tregs that suppresses animal models (experimental autoimmune encephalitis, type 1 and type 2 diabetes, lupus, arthritis, atherosclerosis) and is being tested in humans. Although there is a large literature on treatment of animal models by mucosal tolerance and some positive results in humans, this approach has yet to be translated to the clinic. The successful translation will require defining responsive patient populations, validating biomarkers to measure immunologic effects, and using combination therapy and immune adjuvants to enhance Treg induction. A major avenue being investigated for the treatment of autoimmunity is the induction of Tregs and mucosal tolerance represents a non-toxic, physiologic approach to reach this goal.

Weiner, Howard L.; Cunha, Andre Pires da; Quintana, Francisco; Wu, Henry



Chemotherapy of advanced malignant teratomas.  

PubMed Central

Between 1977 and November 1979 we have treated 53 patients with malignant teratomas (43 males, 10 females). Thirty (70%) out of the 43 male patients had advanced and bulky disease at the time of presentation. Using different drug combinations in a sequential manner as described below, results are as follows: of the initial 33 male patients, 22 (67%) have discontinued treatment (mean 9.5 months). Nineteen have responded completely and 3 have static computed tomography (CT) nodules. Life-table analysis projects a survival of 66% (analysis at 1 December 1979). Nine out of 10 ovarian teratoma patients are alive. Adverse prognostic factors at the start of treatment were recognized in 9/10 male patients and the 1 female patient who have died. Although the survival of patients with malignant teratomas has improved dramatically, there are still problems with drug resistance in patients with very advanced disease. Patients with these tumours should continue to be treated in centres specializing in managing what has now become a potentially curable disease in most cases.

Newlands, E. S.; Begent, R. H.; Kaye, S. B.; Rustin, G. J.; Bagshawe, K. D.



Impacts of CA9 Gene Polymorphisms and Environmental Factors on Oral-Cancer Susceptibility and Clinicopathologic Characteristics in Taiwan  

PubMed Central

Background In Taiwan, oral cancer has causally been associated with environmental carcinogens. Carbonic anhydrase 9 (CA9) is reportedly overexpressed in several types of carcinomas and is generally considered a marker of malignancy. The current study explored the combined effect of CA9 gene polymorphisms and exposure to environmental carcinogens on the susceptibility of developing oral squamous cell carcinoma (OSCC) and the clinicopathological characteristics of the tumors. Methodology and Principal Findings Four single-nucleotide polymorphisms (SNPs) of the CA9 gene from 462 patients with oral cancer and 519 non-cancer controls were analyzed by a real-time polymerase chain reaction (PCR). While the studied SNPs (CA9 rs2071676, rs3829078, rs1048638 and +376 Del) were not associated with susceptibility to oral cancer, the GAA haplotype of 3 CA9 SNPs (rs2071676, rs3829078, and rs1048638) was related to a higher risk of oral cancer. Moreover, the four CA9 SNPs combined with betel quid chewing and/or tobacco consumption could robustly elevate susceptibility to oral cancer. Finally, patients with oral cancer who had at least one G allele of CA9 rs2071676 were at higher risk for developing lymph-node metastasis (p?=?0.022), compared to those patients homozygous for AA. Conclusions Our results suggest that the haplotype of rs2071676, rs3829078, and rs1048638 combined has potential predictive significance in oral carcinogenesis. Gene-environment interactions of CA9 polymorphisms, smoking, and betel-quid chewing might alter oral cancer susceptibility and metastasis.

Chien, Ming-Hsien; Yang, Jia-Sin; Chu, Yin-Hung; Lin, Chien-Huang; Wei, Lin-Hung; Yang, Shun-Fa; Lin, Chiao-Wen



Fascin-1 expression in canine cutaneous and oral melanocytic tumours.  


Fascin-1 expression was examined in 9 cutaneous melanocytomas and 47 oral melanomas. The cases were scored on the basis of extent and intensity of staining, and combined scores were calculated. Fascin-1 expression was observed in 5/9 (56%) melanocytomas and 46/47 (98%) melanomas. The combined score for fascin-1 was significantly greater in stage III/IV melanomas than in stage I/II melanomas (P < 0.05). In addition, strong fascin-1 staining was associated with a significantly shortened survival time (P < 0.05). The results of this study suggest that fascin-1 overexpression correlates with the malignancy of canine melanoma and has the potential to be a new immunohistochemical marker to predict the clinical course of canine melanoma. In addition, targeted therapy for fascin-1 may represent a new strategy for the treatment of canine melanoma. PMID:22236355

Yamada, N; Mori, T; Murakami, M; Noguchi, S; Sakai, H; Akao, Y; Maruo, K



Fate of polymeric nanocarriers for oral drug delivery  

Microsoft Academic Search

This review will focus on two polymeric nanocarriers: nanoparticles and micelles that have been studied for oral drug delivery at preclinical level. Their potential for oral drug delivery will first be illustrated. Then their mechanisms of uptake and their fate after oral delivery will be discussed. Future directions for oral delivery with nanocarriers will be analyzed with a special emphasis

Laurence Plapied; Nicolas Duhem; Anne des Rieux; Véronique Préat



Characteristics of a cancerous cell line, HIOEC-B(a)P-96, induced by benzo(a)pyrene from human immortalized oral epithelial cell line  

Microsoft Academic Search

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the oral and maxillofacial region. The mechanism of carcinogenesis of OSCC is still unclear. In vitro study on OSCC cell lines, especially derived from immortalized oral epithelial cells, is a very useful strategy to understand the mechanism of carcinogenesis. Based on our previous human immortalized oral epithelial cell

Lai-Ping Zhong; Hong-Ya Pan; Xiao-Jian Zhou; Dong-Xia Ye; Lei Zhang; Xiao Yang; Wan-Tao Chen; Zhi-Yuan Zhang



Cytochrome p450 metabolism of betel quid-derived compounds: implications for the development of prevention strategies for oral and pharyngeal cancers.  


Betel quid (BQ) products, with or without tobacco, have been classified by the International Agency for Research on Cancer (IARC) as group I human carcinogens that are associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. There are estimated 600 million BQ users worldwide. In Taiwan alone there are 2 million habitual users (approximately 10% of the population). Oral and pharyngeal cancers result from interactions between genes and environmental factors (BQ exposure). Cytochrome p450 (CYP) families are implicated in the metabolic activation of BQ- and areca nut-specific nitrosamines. In this review, we summarize the current knowledge base regarding CYP genetic variants and related oral disorders. In clinical applications, we focus on cancers of the oral cavity and pharynx and OPMDs associated with CYP gene polymorphisms, including CYP1A1, CYP2A6, CYP2E1, and CYP26B1. Our discussion of CYP polymorphisms provides insight into the importance of screening tests in OPMDs patients for the prevention of oral and pharyngeal cancers. Future studies will establish a strong foundation for the development of chemoprevention strategies, polymorphism-based clinical diagnostic tools (e.g., specific single-nucleotide polymorphism (SNP) "barcodes"), and effective treatments for BQ-related oral disorders. PMID:23983642

Lin, Che-Yi; Pan, Tien-Szu; Ting, Chun-Chan; Liang, Shih-Shin; Huang, Shu-Hung; Liu, Hsiu-Yueh; Ko, Edward Cheng-Chuan; Wu, Chung-Wei; Tang, Jen-Yang; Chen, Ping-Ho



Lymphoscintigraphy in malignant melanoma  

SciTech Connect

The development and rationale for the use of lymphoscintigraphy in the preoperative evaluation of patients with malignant melanoma being considered for elective lymph node dissection is reviewed. This overview is updated by an analysis of 135 patients with early stage malignant melanoma involving the head, neck, shoulders, and trunk at Moffitt Cancer Center and Research Institute at the University of South Florida (Tampa, FL). High discordancy rates (overall, 41%) were seen between drainage patterns predicted from historical anatomical guidelines and those revealed by the lymphoscintigraphic examination. The high discordancy rate was most pronounced in the head (64%) and the neck (73%). Surgical management was changed in 33% of the patients, overall. A preoperative lymphoscintigram is recommended for all patients with melanoma with head, neck, and truncal lesions evaluated for elective lymph node dissection as the lymphatic drainage patterns are often unpredictable and variable.

Berman, C.G.; Norman, J.; Cruse, C.W.; Reintgen, D.S.; Clark, R.A. (Department of Radiology, H. Lee Moffitt Cancer Center, Tampa, FL (United States))



Microbiome and Malignancy  

PubMed Central

Current knowledge is insufficient to explain why only a proportion of individuals exposed to environmental carcinogens or carrying a genetic predisposition to cancer develop disease. Clearly, other factors must be important and one such element that has recently received attention is the human microbiome, the residential microbes including Bacteria, Archaea, Eukaryotes, and viruses that colonize humans. Here, we review principles and paradigms of microbiome-related malignancy, as illustrated by three specific microbial-host interactions. We review the effects of the microbiota on local and adjacent-neoplasia, present the estrobolome model of distant effects, and discuss the complex interactions with a latent virus leading to malignancy. These are separate facets of a complex biology interfacing all the microbial species we harbor from birth onward toward early reproductive success and eventual senescence.

Plottel, Claudia S.; Blaser, Martin J.



Oral antiresorptive therapy  

Microsoft Academic Search

Oral antiresorptive agents play a pivotal role in the management of osteoporosis. This paper discusses the effects and potential\\u000a future role of newer agents such as ibandronate. Alternative dosing schedules and routes of administration have become available\\u000a and may improve fracture protection, compliance, and tolerability for the long term treatment of a chronic condition such\\u000a as osteoporosis. Increasingly these agents

Ira Pande; David J. Hosking