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Sample records for oral potentially malignant

  1. Potentially malignant oral lesions: clinicopathological correlations

    PubMed Central

    Maia, Haline Cunha de Medeiros; Pinto, Najara Alcântara Sampaio; Pereira, Joabe dos Santos; de Medeiros, Ana Miryam Costa; da Silveira, Éricka Janine Dantas; Miguel, Márcia Cristina da Costa

    2016-01-01

    ABSTRACT Objective To determine the incidence of potentially malignant oral lesions, and evaluate and correlate their clinical and pathological aspects. Methods The sample consisted of cases clinically diagnosed as oral leukoplakia, oral erythroplakia, erythroleukoplakia, actinic cheilitis, and oral lichen planus treated at a diagnostic center, between May 2012 and July 2013. Statistical tests were conducted adopting a significance level of 5% (p≤0.05). Results Out of 340 patients, 106 (31.2%) had potentially malignant oral lesions; and 61 of these (17.9%) were submitted to biopsy. Actinic cheilitis was the most frequent lesion (37.5%) and the lower lip was the most affected site (49.6%). Among 106 patients in the sample, 48 (45.3%) reported nicotine consumption, 35 (33%) reported alcohol intake and 34 (32.1%) sun exposure while working. When clinical and histopathological diagnoses were compared, oral erythroplakia and atypical ulcer were the lesions that exhibited greater compatibility (100% each). Conclusion In most cases, clinical and histopathological diagnoses were compatible. An association between the occurrence of erythroplakia, leukoplakia and erythroleukoplakia with smoking was observed. Similarly, an association between actinic cheilitis and sun exposure was noted. Erythroleukoplakia presented the highest malignancy grade in this study. Finally, dental surgeons should draw special attention to diagnosis of potentially malignant oral lesions, choose the best management, and control the lesions to avoid their malignant transformation. PMID:27074232

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

    PubMed Central

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

    2013-01-01

    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. PMID:24078812

  3. Quantitative Immunoexpression of EGFR in Oral Potentially Malignant Disorders: Oral Leukoplakia and Oral Submucous Fibrosis.

    PubMed

    Jyothi Meka, Naga; Ugrappa, Sridevi; Velpula, Nagalaxmi; Kumar, Sravan; Naik Maloth, Kotya; Kodangal, Srikanth; Ch, Lalitha; Goyal, Stuti

    2015-01-01

    Background and aims. Many oral squamous cell carcinomas develop from potentially malignant disorders (PMDs)which include a variety of lesions and conditions characterized by an increased risk for malignant transformation. Thisstudy evaluated the quantitative expression of EGFR in normal oral mucosa, oral leukoplakia and oral submucous fibrosis to predict the malignant risk in compliance with the intensity of staining with EGFR. Materials and methods. Thirty subjects were included in the study, consisting of 10 oral leukoplakia (OL), 10 oral submucous fibrosis (OSMF) and 10 normal oral mucosa (NOM) as the control group. Owing to the histopathological confirmation of precancerous state of tissue, 4-μm-thick sections of tissue were taken from paraffin-embedded wax blocks for immunohistochemical staining for EGFR. Results. All the control cases showed positive expression for EGFR, while 20% of oral leukoplakia and 40% of OSMF cases showed strong expression (3+), 40% of OL and 30% of OSMF cases showed weak expression (2+), and 40% of OLand 30% of OSMF cases showed poor expression (1+) compared to controls (P=0.012). Conclusion. EGFR expression levels in the premalignant lesion appear to be a sensitive factor in predicting the neoplastic potential. This suggests that EGFR may serve as a biological marker to identify high-risk subgroups and guide prophylactic therapy with chemopreventive drugs or surgical intervention to prevent progression to carcinoma. Hence, further investigations in the direction of chemopreventive trials with a larger sample size are suggested to determine its role in the head and neck tumorigenesis. PMID:26697149

  4. HBO: a possible supplementary therapy for oral potentially malignant disorders.

    PubMed

    Ye, Xiaojing; Zhang, Jing; Lu, Rui; Zhou, Gang

    2014-08-01

    Oral potentially malignant disorders (OPMDs) are chronic inflammatory diseases in which cells suffer hypoxia referring to deprivation of adequate oxygen supply. Hyperbaric oxygen treatment (HBO), which can increase oxygen tension and delivery to oxygen-deficient tissue, is a supplementary therapy to improve or cure disorders involving hypoxia. Although the applications of HBO in wound healings, acute ischemic stroke, radiation-induced soft tissue injury and cancers are extensively reported, there are only few studies on their effect in OPMDs. Not only does HBO furnish oxygen-it also possesses potent anti-inflammatory properties. At the cellular level, HBO can decrease lymphocyte proliferation and promote apoptosis of fibroblasts. At the molecular level, it can decrease expression of HIF, ICAM-1, TNF-α, TGF-β, and IFN-γ, as well as increase vascular VEGF expression and angiogenesis. Thus, we hypothesize that HBO may contribute to treat OPMDs, including oral lichen planus, oral leukoplakia, and oral submucous fibrosis both at the cellular level and the molecular level, and that it would be a safe and inexpensive therapeutic strategy. PMID:24908359

  5. Use of electrical impedance spectroscopy to detect malignant and potentially malignant oral lesions

    PubMed Central

    Murdoch, Craig; Brown, Brian H; Hearnden, Vanessa; Speight, Paul M; D’Apice, Katy; Hegarty, Anne M; Tidy, John A; Healey, T Jamie; Highfield, Peter E; Thornhill, Martin H

    2014-01-01

    The electrical properties of tissues depend on their architecture and cellular composition. We have previously shown that changes in electrical impedance can be used to differentiate between different degrees of cervical dysplasia and cancer of the cervix. In this proof-of-concept study, we aimed to determine whether electrical impedance spectroscopy (EIS) could distinguish between normal oral mucosa; benign, potentially malignant lesions (PML); and oral cancer. EIS data were collected from oral cancer (n=10), PML (n=27), and benign (n=10) lesions. EIS from lesions was compared with the EIS reading from the normal mucosa on the contralateral side of the mouth or with reference spectra from mucosal sites of control subjects (n=51). Healthy controls displayed significant differences in the EIS obtained from different oral sites. In addition, there were significant differences in the EIS of cancer and high-risk PML versus low-risk PML and controls. There was no significant difference between benign lesions and normal controls. Study subjects also deemed the EIS procedure considerably less painful and more convenient than the scalpel biopsy procedure. EIS shows promise at distinguishing among malignant, PML, and normal oral mucosa and has the potential to be developed into a clinical diagnostic tool. PMID:25285005

  6. Prevalence and Risk Factors for Oral Potentially Malignant Disorders in Indian Population

    PubMed Central

    Kumar, Sandeep; Debnath, Nitai; Ismail, Mohammed B.; Kumar, Arunoday; Kumar, Amit; Badiyani, Bhumika K.; Dubey, Pavan K.; Sukhtankar, Laxmi V.

    2015-01-01

    Objective. To assess the prevalence of oral potentially malignant disorders and to determine the potential risk factors for its development in Indian population. Materials and Methods. This cross-sectional study was carried out on 1241 individuals in Indore, Madhya Pradesh. A questionnaire was designed to record information about sociodemographic characteristics, oral hygiene practices, dietary habits, and risk factors for oral potentially malignant disorders. Oral mucosal lesions were examined by a skilled person. Results. The overall prevalence of oral potentially malignant disorders was found to be 13.7% with oral submucous fibrosis (8.06%) found to be more common and erythroplakia (0.24%) found to be least prevalent. Results of Logistic Regression analysis showed that males (OR = 2.09, P value < 0.0001) who were ever consumers of tobacco (OR = 2.06, P value = 0.030) and areca nut chewing (OR = 2.64, P value = 0.004) were more likely to develop oral potentially malignant disorders compared to never consumers. Diabetic (OR = 2.21, P value = 0.014) and underweight individuals (OR = 2.23, P value = 0.007) were more likely to suffer from oral potentially malignant disorders. Conclusion. The study reinforces the association of tobacco and areca nut consumption with oral potentially malignant disorders. An association of oral potentially malignant disorders with diabetes and BMI was confirmed by this study. PMID:26347822

  7. Oral Potentially Malignant Disorders: An Overview of More than 20 Entities

    PubMed Central

    Mortazavi, Hamed; Baharvand, Maryam; Mehdipour, Masoumeh

    2014-01-01

    Cancer of the oral cavity accounts for approximately 3% of all malignancies diagnosed annually in 270,000 patients world-wide. Oral cancer is the 12th most common cancer in women and the 6th in men. Many oral squamous cell carcinomas develop from potentially malignant disorders (PMDs). Lack of awareness about the signs and symptoms of oralPMDs in the general population and even healthcare providers is believed to be responsible for the diagnostic delay of these entities. The aim of this article is to update and improve the knowledge of healthcare providers about oral PMDs. PMID:25024833

  8. Ability of Dental Students in Spain to Identify Potentially Malignant Disorders and Oral Cancer.

    PubMed

    Cerero-Lapiedra, Rocío; Esparza-Gómez, Germán C; Casado-de la Cruz, Laura; Domínguez-Gordillo, Adelaida A; Corral-Linaza, César; Seoane-Romero, Juan M

    2015-08-01

    The aim of this study was to assess the ability of students at the School of Dentistry, Complutense University of Madrid, Spain, to diagnose oral cancer and other potentially malignant disorders, as well as to compare their ability at different stages of the learning process and evaluate their knowledge retention. Students were surveyed after they had studied oral medicine and oral pathology at two time points: midway through and near the end of their studies. The survey consisted of questions about 40 photographs of benign oral lesions, malignant oral lesions, and potentially malignant disorders. The response rate for all groups was greater than 70%. The results showed that these students' overall success rate in differentiating benign from malignant lesions averaged 73.9%. When the distinction for potentially malignant disorders was included, their average overall success rate decreased to 42.8% (p<0.001). Furthermore, the students' average success rate was at its lowest at the end of the dental program (p<0.001). Results from this study suggest that, given these students' difficulties in identifying potentially malignant disorders, an increased emphasis on cancer education in the dental curriculum may be needed for future practitioners to master this ability. PMID:26246535

  9. Non-Invasive Techniques for Detection and Diagnosis of Oral Potentially Malignant Disorders.

    PubMed

    Liu, Dongjuan; Zhao, Xin; Zeng, Xin; Dan, Hongxia; Chen, Qianming

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is the most common oral and maxillofacial malignancy, and its morbidity and mortality rates are still high in most countries. Oral potentially malignant disorders (PMDs) are used to refer to a heterogeneous group of conditions that are characterized by increased risk for malignant transformation to OSCC. Currently identified oral PMDs include leukoplakia, erythroplakia, palatal lesions associated with reverse smoking, oral lichen planus, oral submucous fibrosis, actinic keratosis, and discoid lupus erythematosus. The early detection and diagnosis of these lesions are important for cancer prevention and disease management. In recent years, there has been a growing and persistent demand for new non-invasive, practical diagnostic techniques that might facilitate the early detection of oral PMDs. The non-invasive detection techniques evaluated in this review are divided into four categories: vital staining with a solution that can be used as a mouth rinse or applied onto a suspected area of the mouth, light-based detection systems, optical diagnostic technologies that employ returned optical signals to reflect structural and morphological changes within tissues, and salivary biomarkers. Most of these techniques have shown great potential for screening and monitoring oral PMDs. In this review article, the authors critically assess these non-invasive detection techniques for oral PMDs. We also provide a summary of the sensitivity and specificity of each technique in detecting oral PMDs and oral cancer, as well as their advantages, disadvantages, clinical applications, and indications. PMID:26888696

  10. Optical imaging for the diagnosis of oral cancer and oral potentially malignant disorders

    NASA Astrophysics Data System (ADS)

    Yoshida, K.

    2016-03-01

    Optical Imaging is being conducted as a therapeutic non-invasive. Many kinds of the light source are selected for this purpose. Recently the oral cancer screening is conducted by using light-induced tissue autofluorescence examination such as several kinds of handheld devices. However, the mechanism of its action is still not clear. Therefore basic experimental research was conducted. One of auto fluorescence Imaging (AFI) device, VELscopeTM and near-infrared (NIR) fluorescence imaging using ICG-labeled antibody as a probe were compared using oral squamous cell carcinoma (OSCC) mouse models. The experiments revealed that intracutaneous tumor was successfully visualized as low density image by VELscopeTM and high density image by NIR image. In addition, VELscopeTM showed higher sensitivity and lower specificity than that of NIR fluorescence imaging and the sensitivity of identification of carcinoma areas with the VELscopeTM was good results. However, further more studies were needed to enhance the screening and diagnostic uses, sensitivity and specificity for detecting malignant lesions and differentiation from premalignant or benign lesions. Therefore, additional studies were conducted using a new developed near infrared (NIR) fluorescence imaging method targeting podoplanine (PDPN) which consists of indocyanine green (ICG)-labeled anti-human podoplanin antibody as a probe and IVIS imaging system or a handy realtime ICG imaging device that is overexpressed in oral malignant neoplasm to improve imaging for detection of early oral malignant neoplasm. Then evaluated for its sensitivity and specificity for detection of oral malignant neoplasm in xenografted mice model and compared with VELscopeTM. The results revealed that ICG fluorescence imaging method and VELscopeTM had the almost the same sensitivity for detection of oral malignant neoplasm. The current topics of optical imaging about oral malignant neoplasm were reviewed.

  11. Prevalence of salivary epstein-barr virus in potentially malignant oral disorders and oral squamous cell carcinoma

    PubMed Central

    Ocete-Monchon, María-Dolores; Leopoldo-Rodado, Manuel; Murillo-Cortes, Judith; Díaz-Fernández, Jose-M.; Medina-Gonzalez, Rafael; Gimeno-Cardona, Concepción; Bagan, Jose-V.

    2016-01-01

    Background To analyze the presence of salivary Epstein-Barr virus (EBV) DNA in oral squamous cell carcinoma and potentially malignant oral disorders. Material and Methods Three groups were studied: Group 1 (12 oral squamous cell carcinomas (OSCC)), Group 2 (12 potentially malignant oral disorders (PMD)) and Group 3 (47 healthy controls). EBV DNA salivary analysis was performed by PCR. Results The highest percentage of positive salivary EBV DNA corresponded to the OSCC group (58.3%), followed by the PMD group (41.7%) and the controls (40.4%). The differences between groups were not statistically significant, however (p>0.05). Conclusions Salivary EBV DNA was more prevalent in OSCC than in PMD or the controls. Key words:EBV DNA, saliva, oral squamous cell carcinoma, oral leukoplakia. PMID:26827058

  12. Betel Quid and Oral Potentially Malignant Disorders in a Periurban Township in Myanmar.

    PubMed

    Zaw, Ko-Ko; Ohnmar, Mya; Hlaing, Moh-Moh; Oo, Yin-Thet-Nu; Win, Swe-Swe; Htike, Maung-Maung-Than; Aye, Phyu-Phyu; Shwe, Sein; Htwe, Moe-Thida; Thein, Zaw-Moe

    2016-01-01

    This study aims to describe betel quid chewing practice and compare oral potentially malignant disorders between chewers and non-chewers of betel quid among residents in Dagon Myothit (East) Township, Myanmar. The study used a cross-sectional design conducted with a representative sample of 542 adults aged 18 years and above in the township. The trained interviewers collected data using a pretested structured questionnaire. On-site oral examination was done for suspected oral lesions. The mean age of the respondents was 45 years and 59% were women. Fifty-two percent of the respondents were currently in the habit of chewing betel quids (72% of men and 39% of women). Among 284 current betel quid chewers, 240 (85%) chewed betel quids together with tobacco. Out of 284 current betel quid chewers, 24 (8.5%) were found to have oral potentially malignant disorders; out of 258 betel quid non-chewers, only 1 (0.4%) was found to have oral potentially malignant disorders. This highlights the growing importance of smokeless tobacco use as public health problem.

  13. Betel Quid and Oral Potentially Malignant Disorders in a Periurban Township in Myanmar.

    PubMed

    Zaw, Ko-Ko; Ohnmar, Mya; Hlaing, Moh-Moh; Oo, Yin-Thet-Nu; Win, Swe-Swe; Htike, Maung-Maung-Than; Aye, Phyu-Phyu; Shwe, Sein; Htwe, Moe-Thida; Thein, Zaw-Moe

    2016-01-01

    This study aims to describe betel quid chewing practice and compare oral potentially malignant disorders between chewers and non-chewers of betel quid among residents in Dagon Myothit (East) Township, Myanmar. The study used a cross-sectional design conducted with a representative sample of 542 adults aged 18 years and above in the township. The trained interviewers collected data using a pretested structured questionnaire. On-site oral examination was done for suspected oral lesions. The mean age of the respondents was 45 years and 59% were women. Fifty-two percent of the respondents were currently in the habit of chewing betel quids (72% of men and 39% of women). Among 284 current betel quid chewers, 240 (85%) chewed betel quids together with tobacco. Out of 284 current betel quid chewers, 24 (8.5%) were found to have oral potentially malignant disorders; out of 258 betel quid non-chewers, only 1 (0.4%) was found to have oral potentially malignant disorders. This highlights the growing importance of smokeless tobacco use as public health problem. PMID:27611195

  14. Betel Quid and Oral Potentially Malignant Disorders in a Periurban Township in Myanmar

    PubMed Central

    Zaw, Ko-Ko; Ohnmar, Mya; Hlaing, Moh-Moh; Oo, Yin-Thet-Nu; Win, Swe-Swe; Htike, Maung-Maung-Than; Aye, Phyu-Phyu; Shwe, Sein; Htwe, Moe-Thida; Thein, Zaw-Moe

    2016-01-01

    This study aims to describe betel quid chewing practice and compare oral potentially malignant disorders between chewers and non-chewers of betel quid among residents in Dagon Myothit (East) Township, Myanmar. The study used a cross-sectional design conducted with a representative sample of 542 adults aged 18 years and above in the township. The trained interviewers collected data using a pretested structured questionnaire. On-site oral examination was done for suspected oral lesions. The mean age of the respondents was 45 years and 59% were women. Fifty-two percent of the respondents were currently in the habit of chewing betel quids (72% of men and 39% of women). Among 284 current betel quid chewers, 240 (85%) chewed betel quids together with tobacco. Out of 284 current betel quid chewers, 24 (8.5%) were found to have oral potentially malignant disorders; out of 258 betel quid non-chewers, only 1 (0.4%) was found to have oral potentially malignant disorders. This highlights the growing importance of smokeless tobacco use as public health problem. PMID:27611195

  15. Efficacy of light based detection systems for early detection of oral cancer and oral potentially malignant disorders: Systematic review

    PubMed Central

    Reddy-Kantharaj, Yashoda-Bhoomi; Rakesh, Nagaraju; Janardhan-Reddy, Sujatha; Sahu, Shashikant

    2016-01-01

    Background Earlier detection of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) is essential for dental professionals to improve patient survival rates. The aim of this systematic review is to to evaluate the effectiveness of devices that utilise the principles of chemiluminescence and tissue autofluorescence as adjuncts in the detection of OSCC and OPMD. Material and Methods The electronic retrieval systems and databases searched for relevant articles were PubMed [MEDLINE] and Science direct. The search was for limited articles published in English or with an English abstract and articles published during the period from January 2005 to April 2014. Clinical trials utilized ViziLite, Microlux TM/DL and Visual Enhanced Light scope (VELscope) for early detection of OPMD and OSCC. Results Twenty primary studies published satisfied our criteria for selection - 10 utilised chemiluminescence and 10 tissue autofluorescence. Senstivity of Vizilite for detecting OSCC nad OPMD ranged from 77.1 % to 100% and specificity was low that ranged from 0% to 27.8%.Most have shown that chemiluminescence increases the brightness and margins of oral mucosal white lesions and thus assist in identification of mucosal lesions not considered under Conventional visual examination. However, it preferentially detects leukoplakia and may fail to spot red patches. Clinical trials demonstrated that sensitivity of VELscope in detecting malignancy and OPMD ranged from 22 % to 100 % and specificity ranged from 16 % to 100%. Most studies concluded that VELscope can help the experienced clinician to find oral precursor malignant lesions. But it couldnot differentiate between dysplasia and benign inflammatory conditions. Conclusions Both devices are simple, non-invasive test of the oral mucosa but are suited for clinicians with sufficient experience and training. More clinical trials in future should be conducted to establish optical imaging as an efficacious adjunct

  16. Screening of Oral Potentially Malignant Disorders Using Exfoliative Cytology: A Diagnostic Modality

    PubMed Central

    Bhowmick, Debarati; Ginjupally, Uday; Bir, Aritri; Chatterjee, Kushal

    2016-01-01

    Objective. Oral exfoliative cytology (OEC) has been implemented in the diagnosis of pathologic lesions for ages. The present study was undertaken to evaluate the cytomorphological features of some of the commonest potentially malignant disorders (leukoplakia, lichen planus, and oral submucous fibrosis) through a simple procedure and illustrate its importance in mass screening. Materials and Method. A total of 160 subjects with 25–50 years of age were included in the study. Among them, 40 were clinically diagnosed with oral leukoplakia, 40 were diagnosed with oral lichen planus, 40 were diagnosed with oral submucous fibrosis, and 40 were in the control group. The prepared smears were subjected to Papanicolaou stain and analyzed microscopically for the evaluation of the cytomorphological features. Results and Discussion. When analyzed microscopically, 36 (90%) out of the 40 oral leukoplakic lesions showed Class II cytological features whereas 4 (10%) revealed Class I features. Among 40 patients with oral lichen planus, 26 (65%) showed Class II features while the remaining 14 (35%) revealed Class I features. In 40 subjects with oral submucous fibrosis, 32 (80%) showed Class II features while the other 8 (20%) showed Class I features. All the 40 control subjects showed Class I features. Thus, OEC can be widely advocated as an addition to clinical conclusion and an adjunct to biopsy. PMID:27721828

  17. Prevalence of potentially malignant oral mucosal lesions among tobacco users in Jeddah, Saudi Arabia.

    PubMed

    Al-Attas, Safia Ali; Ibrahim, Suzan Seif; Amer, Hala Abbas; Darwish, Zeinab El-Said; Hassan, Mona Hassan

    2014-01-01

    Smoking is recognized as a health problem worldwide and there is an established tobacco epidemic in Saudi Arabia as in many other countries, with tobacco users at increased risk of developing many diseases. This cross sectional study was conducted to assess the prevalence of oral mucosal, potentially malignant or malignant, lesions associated with tobacco use among a stratified cluster sample of adults in Jeddah, Saudi Arabia. A sample size of 599 was collected and each participant underwent clinical conventional oral examination and filled a questionnaire providing information on demographics, tobacco use and other relevant habits. The most common form of tobacco used was cigarette smoking (65.6 %) followed by Shisha or Moasel (38.1%), while chewing tobacco, betel nuts and gat accounted for 21-2%, 7.7%, and 5% respectively. A high prevalence (88.8%) of soft tissue lesions was found among the tobacco users examined, and a wide range of lesions were detected, about 50% having hairy tongue, 36% smoker's melanosis, 28.9% stomatitis nicotina, 27% frictional keratosis, 26.7% fissured tongue, 26% gingival or periodontal inflammation and finally 20% leukodema. Suspicious potentially malignant lesions affected 10.5% of the subjects, most prevalent being keratosis (6.3%), leukoplakia (2.3%), erythroplakia (0.7%), oral submucous fibrosis (0.5%) and lichenoid lesions (0.4%), these being associated with male gender, lower level of education, presence of diabetes and a chewing tobacco habit. It is concluded that smoking was associated with a wide range of oral mucosal lesions , those suspicious for malignancy being linked with chewable forms, indicating serious effects.

  18. Expression of matrix metalloproteinase-9 in oral potentially malignant disorders: A systematic review

    PubMed Central

    Venugopal, Archana; Uma Maheswari, TN

    2016-01-01

    Matrix metalloproteinase-9 (MMP-9) is an inducible enzyme. Oral potentially malignant disorders (OPMDs) are considered as the early tissue changes that happen due to various habits such as smoking tobacco, chewing tobacco or stress. This alteration in the tissues alters the expression of MMP-9. The rationale of the review is to know the expression of MMP-9 in OPMDs. Hand searching and electronic databases such as PubMed and ScienceDirect were done for mesh terms such as OPMDs and MMP-9. Eight articles were obtained, after applying inclusion and exclusion criteria. These articles were assessed with QUADAS and data were extracted and evaluated. The included eight studies were done in 182 oral squamous cell carcinoma cases, 430 OPMDs (146 oral lichen planus, 264 leukoplakia and 20 oral submucous fibrosis) and 352 healthy controls evaluated for MMP-9. MMP-9 expression was found to be elevated in tissue, serum and saliva samples of OPMDs than in healthy controls. There is only one study in each serum and saliva samples to evaluate MMP-9. Saliva being noninvasive and serum being minimally invasive, more studies need to be done in both serum and saliva to establish MMP-9 as an early diagnostic marker in OPMDs to know its potential in malignant transformation. PMID:27721614

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

    NASA Astrophysics Data System (ADS)

    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

    2012-02-01

    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.

  20. Programmable Bio-Nano-Chip based Cytologic Testing of Oral Potentially Malignant Disorders in Fanconi Anemia

    PubMed Central

    Floriano, Pierre; Abram, Tim; Taylor, Leander; Le, Cathy; Talavera, Humberto; Nguyen, Michael; Raja, Rameez; Gillenwater, Ann; McDevitt, John; Vigneswaran, Nadarajah

    2015-01-01

    Fanconi anemia (FA) is caused by mutations of DNA repair genes. The risk of oral squamous cell carcinoma (OSCC) among FA patients is 800-folds higher than in the general population. Early detection of OSCC, preferably at it precursor stage is critical in FA patients to improve their survival. In an ongoing clinical trial, we are evaluating the effectiveness of the programmable bio-nano-chip (p-BNC)-based oral cytology test in diagnosing oral potentially malignant disorders (OPMD) in non-FA patients. We used this test to compare the cytomorphometric and molecular biomarkers in OSCC cell lines derived from FA patients and non-FA patients and brush biopsy samples of a FA patient’s OPMD and normal mucosa of healthy volunteers. Our data showed that expression patterns of molecular biomarkers were not notably different between sporadic and FA OSCC cell lines. The p-BNC assay revealed significant differences in cytometric parameters and biomarker MCM2 expression between cytobrush samples of the FA patient and cytobrush samples of normal oral mucosa obtained from healthy volunteers. Microscopic examination of the FA patient’s OPMD confirmed the presence of dysplasia. Our pilot data suggests that p-BNC brush biopsy test recognizes dysplastic oral epithelial cells in a brush biopsy sample of a FA patient. PMID:25662766

  1. Comparative study of frequency of micronuclei in normal, potentially malignant diseases and oral squamous cell carcinoma

    PubMed Central

    Sangle, Varsha Ajit; Bijjaragi, Shobha; Shah, Nishat; Kangane, Suresh; Ghule, Hrishikesh M.; Rani, SR Ashwini

    2016-01-01

    Context: The assessment of micronuclei (MN) in exfoliated oral epithelial cells is a promising tool for the study of epithelial carcinogens and can be used to detect chromosome breakage or mitotic interference, thought to be relevant to carcinogenesis. Aims: To detect MN in exfoliated oral mucosal cells in individuals using various tobacco forms and also to detect frequency of MN in premalignant lesions and conditions (potentially malignant diseases [PMD's]) and oral squamous cell carcinoma (OSCC). To correlate frequency of MN in oral exfoliated cells in clinically diagnosed cases of OSCC followed by a histopathological grading. Materials and Methods: A total of 90 subjects (30 smokeless tobacco users, 30 smokers and 30 nontobacco users) consisted of clinically diagnosed cases of PMD's and OSCC were selected for the study. Cytosmears from the groups were stained with rapid Papanicolaou stain. MN was identified according to the Tolbert et al. criteria. Results: MN cells were found to be significantly higher in smokeless tobacco users than in smokers. The frequency of MN was three to four times higher in patients with OSCC as compared to patients in PMD's (P < 0.0001). The frequency of MN correlated with the histopathological grade was statistically significant. Conclusion: MN index can be used as a biomarker/screening test among the high-risk groups particularly the smokeless tobacco users and PMD's. MN can be a candidate to serve as a biomarker for prediction of the grade of OSCC. PMID:27003966

  2. Expression of MUC1 mucin in potentially malignant disorders, oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study

    PubMed Central

    Kumar, M Harish; Sanjai, Karpagaselvi; Kumarswamy, Jayalakshmi; Keshavaiah, Roopavathi; Papaiah, Lokesh; Divya, S

    2016-01-01

    Background: Mucins alteration in glycosylation is associated with the development and progression of malignant diseases. Therefore, mucins are used as valuable markers to distinguish normal and disease conditions. Many studies on MUC1 expression have been conducted on variety of neoplastic lesions other than head and neck region. None of the study has made an attempt to show its significance in potentially malignant disorders (PMDs) and oral squamous cell carcinoma (OSCC). Hence, ours is one of the pioneer studies done to assess and evaluate the same. Aims: This study aims to compare and correlate the expression of MUC1 mucin protein in normal oral mucosa (NOM), PMD's and OSCC by immunohistochemical method. Materials and Methods: Institutional study, archived tissue sections of OSCC (n = 20), PMD's (n = 20) and NOM (n = 20) were immunostained for MUC1 mucin and percentage of positive cells evaluated. Results obtained were statistically analyzed using Kruskal–Wallis test, Mann–Whitney test and Student's t-test. Results: The mean MUC1 mucin positive cells in the study groups were as follows, 40% in OSCC, 28% in PMD's and 0.75% in NOM. Higher mean immunohistochemical score was observed in OSCC group followed by PMD's group and NOM group. The difference in immunohistochemical score among the groups was found to be statistically significant (P < 0.001). Conclusion: The result of the current study suggests that determination of MUC1 mucin expression may be a parameter in the diagnosis of malignant behavior of PMD's to OSCC. MUC1 mucin expression may be a useful diagnostic marker for prediction of the invasive/metastatic potential of OSCC. PMID:27601811

  3. Potential of optical coherence tomography for early diagnosis of oral malignancies

    PubMed Central

    DeCoro, Michael; Wilder-Smith, Petra

    2014-01-01

    With nearly 1,500,000 new patients diagnosed every year in the USA, cancer poses a considerable challenge to healthcare today. Oral cancer is responsible for a sizeable portion of deaths due to cancer, primarily because it is diagnosed at a late stage when the prognosis is poor. Current methods for diagnosing oral cancer need to be augmented by better early detection, monitoring and screening modalities. A new approach is needed that provides real-time, accurate, noninvasive diagnosis. The results of early clinical trials using in vivo optical coherence tomography for the diagnosis of oral dysplasia and malignancy are encouraging. PMID:20214513

  4. Fluorescence spectroscopy for the detection of potentially malignant disorders of the oral cavity: analysis of 30 cases

    NASA Astrophysics Data System (ADS)

    Francisco, A. L. N.; Correr, W. R.; Azevedo, L. H.; Galletta, V. K.; Pinto, C. A. L.; Kowalski, L. P.; Kurachi, C.

    2014-01-01

    Oral cancer is a major health problem worldwide and although early diagnosis of potentially malignant and malignant diseases is associated with better treatment results, a large number of cancers are initially misdiagnosed, with unfortunate consequences for long-term survival. Fluorescence spectroscopy is a noninvasive modality of diagnostic approach using induced fluorescence emission in tumors that can improve diagnostic accuracy. The objective of this study was to determine the ability to discriminate between normal oral mucosa and potentially malignant disorders by fluorescence spectroscopy. Fluorescence investigation under 408 and 532 nm excitation wavelengths was performed on 60 subjects, 30 with potentially malignant disorders and 30 volunteers with normal mucosa. Data was analyzed to correlate fluorescence patterns with clinical and histopathological diagnostics. Fluorescence spectroscopy used as a point measurement technique resulted in a great variety of spectral information. In a qualitative analysis of the fluorescence spectral characteristics of each type of injury evaluated, it was possible to discriminate between normal and abnormal oral mucosa. The results show the potential use of fluorescence spectroscopy for an improved discrimination of oral disorders.

  5. Leuloplakia - Review of A Potentially Malignant Disorder

    PubMed Central

    Abidullah, Mohammed; Gaddikeri, Kavitha; Raghoji, Swetha; Ravishankar T, Shilpa

    2014-01-01

    Leukoplakias are oral white lesions that have not been diagnosed as any other specific disease. They are grouped under premalignant lesions, now redesignated as potentially malignant disorders. Their significance lies in the fact that they have propensity for malignant transformation at a higher rate when compared to other oral lesions. This article reviews aetiology, epidemiology, clinical characteristics, histopathologic features, malignant potential and treatment of oral leukoplakia. PMID:25302287

  6. Accuracy of autofluorescence in diagnosing oral squamous cell carcinoma and oral potentially malignant disorders: a comparative study with aero-digestive lesions

    PubMed Central

    Luo, Xiaobo; Xu, Hao; He, Mingjing; Han, Qi; Wang, Hui; Sun, Chongkui; Li, Jing; Jiang, Lu; Zhou, Yu; Dan, Hongxia; Feng, Xiaodong; Zeng, Xin; Chen, Qianming

    2016-01-01

    Presently, various studies had investigated the accuracy of autofluorescence in diagnosing oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) with diverse conclusions. This study aimed to assess its accuracy for OSCC and OPMD and to investigate its applicability in general dental practice. After a comprehensive literature search, a meta-analysis was conducted to calculate the pooled diagnostic indexes of autofluorescence for premalignant lesions (PML) and malignant lesions (ML) of the oral cavity, lung, esophagus, stomach and colorectum and to compute indexes regarding the detection of OSCC aided by algorithms. Besides, a u test was performed. Twenty-four studies detecting OSCC and OPMD in 2761 lesions were included. This demonstrated that the overall accuracy of autofluorescence for OSCC and OPMD was superior to PML and ML of the lung, esophagus and stomach, slightly inferior to the colorectum. Additionally, the sensitivity and specificity for OSCC and OPMD were 0.89 and 0.8, respectively. Furthermore, the specificity could be remarkably improved by additional algorithms. With relatively high accuracy, autofluorescence could be potentially applied as an adjunct for early diagnosis of OSCC and OPMD. Moreover, approaches such as algorithms could enhance its specificity to ensure its efficacy in primary care. PMID:27416981

  7. Fibroblast Growth Factor (FGF-2) and Its Receptors FGFR-2 and FGFR-3 May Be Putative Biomarkers of Malignant Transformation of Potentially Malignant Oral Lesions into Oral Squamous Cell Carcinoma

    PubMed Central

    Nayak, Seema; Goel, Madhu Mati; Makker, Annu; Bhatia, Vikram; Chandra, Saumya; Kumar, Sandeep; Agarwal, S. P.

    2015-01-01

    There are several factors like angiogenesis, lymphangiogenesis, genetic alterations, mutational factors that are involved in malignant transformation of potentially malignant oral lesions (PMOLs) to oral squamous cell carcinoma (OSCC). Fibroblast growth factor-2 (FGF-2) is one of the prototypes of the large family of growth factors that bind heparin. FGF-2 induces angiogenesis and its receptors may play a role in synthesis of collagen. FGFs are involved in transmission of signals between the epithelium and connective tissue, and influence growth and differentiation of a wide variety of tissue including epithelia. The present study was undertaken to analyze expression of FGF-2 and its receptors FGFR-2 and FGFR-3 in 72 PMOLs, 108 OSCC and 52 healthy controls, and their role in risk assessment for malignant transformation of Leukoplakia (LKP) and Oral submucous fibrosis (OSMF) to OSCC. Immunohistochemistry was performed using antibodies against FGF-2, FGFR-2 and FGFR-3. IHC results were validated by Real Time PCR. Expression of FGF-2, FGFR-2 and FGFR-3 was upregulated from PMOLs to OSCC. While 90% (9/10) of PMOLs which showed malignant transformation (transformed) expressed FGF-2, only 24.19% cases (15/62) of PMOLs which were not transformed (untransformed) to OSCC expressed FGF-2. Similarly, FGFR-2 expression was seen in 16/62 (25.81%) of untransformed PMOLs and 8/10 (80%) cases of transformed PMOLs. FGFR-3 expression was observed in 23/62 (37.10%) cases of untransformed PMOLs and 6/10 (60%) cases of transformed PMOLs. A significant association of FGF-2 and FGFR-2 expression with malignant transformation from PMOLs to OSCC was observed both at phenotypic and molecular level. The results suggest that FGF-2 and FGFR-2 may be useful as biomarkers of malignant transformation in patients with OSMF and LKP. PMID:26465941

  8. Fibroblast Growth Factor (FGF-2) and Its Receptors FGFR-2 and FGFR-3 May Be Putative Biomarkers of Malignant Transformation of Potentially Malignant Oral Lesions into Oral Squamous Cell Carcinoma.

    PubMed

    Nayak, Seema; Goel, Madhu Mati; Makker, Annu; Bhatia, Vikram; Chandra, Saumya; Kumar, Sandeep; Agarwal, S P

    2015-01-01

    There are several factors like angiogenesis, lymphangiogenesis, genetic alterations, mutational factors that are involved in malignant transformation of potentially malignant oral lesions (PMOLs) to oral squamous cell carcinoma (OSCC). Fibroblast growth factor-2 (FGF-2) is one of the prototypes of the large family of growth factors that bind heparin. FGF-2 induces angiogenesis and its receptors may play a role in synthesis of collagen. FGFs are involved in transmission of signals between the epithelium and connective tissue, and influence growth and differentiation of a wide variety of tissue including epithelia. The present study was undertaken to analyze expression of FGF-2 and its receptors FGFR-2 and FGFR-3 in 72 PMOLs, 108 OSCC and 52 healthy controls, and their role in risk assessment for malignant transformation of Leukoplakia (LKP) and Oral submucous fibrosis (OSMF) to OSCC. Immunohistochemistry was performed using antibodies against FGF-2, FGFR-2 and FGFR-3. IHC results were validated by Real Time PCR. Expression of FGF-2, FGFR-2 and FGFR-3 was upregulated from PMOLs to OSCC. While 90% (9/10) of PMOLs which showed malignant transformation (transformed) expressed FGF-2, only 24.19% cases (15/62) of PMOLs which were not transformed (untransformed) to OSCC expressed FGF-2. Similarly, FGFR-2 expression was seen in 16/62 (25.81%) of untransformed PMOLs and 8/10 (80%) cases of transformed PMOLs. FGFR-3 expression was observed in 23/62 (37.10%) cases of untransformed PMOLs and 6/10 (60%) cases of transformed PMOLs. A significant association of FGF-2 and FGFR-2 expression with malignant transformation from PMOLs to OSCC was observed both at phenotypic and molecular level. The results suggest that FGF-2 and FGFR-2 may be useful as biomarkers of malignant transformation in patients with OSMF and LKP. PMID:26465941

  9. Potential Use of Quantitative Tissue Phenotype to Predict Malignant Risk for Oral Premalignant Lesions

    PubMed Central

    Guillaud, Martial; Zhang, Lewei; Poh, Catherine; Rosin, Miriam P.; MacAulay, Calum

    2009-01-01

    The importance of early diagnosis in improving mortality and morbidity rates of oral squamous cell carcinoma (SCC) has long been recognized. However, a major challenge for early diagnosis is our limited ability to differentiate oral premalignant lesions (OPLs) at high risk of progressing into invasive SCC from those at low risk. We investigated the potential of Quantitative Tissue Phenotype (QTP), measured by high-resolution image analysis, to recognize severe dysplasia/carcinoma in situ (CIS) (known to have an increased risk of progression) and to predict progression within hyperplasia or mild/moderate dysplasia (termed HMD). We generated a Nuclear Phenotypic Score (NPS), a combination of 5 nuclear morphometric features that best discriminate 4,027 “normal” nuclei (selected from 29 normal oral biopsies) from 4,298 “abnormal” nuclei (selected from 30 SCC biopsies). This NPS was then determined for a set of 69 OPLs. Severe dysplasia/CIS, showed a significant increase in NPS compared to HMD. However, within the latter group, elevated NPS was strongly associated with the presence of high-risk LOH patterns. There was a statistical difference between NPS of HMD that progressed to cancer and those that did not. Individuals with a high NPS had a 10-fold increase in relative risk of progression. In the multivariate Cox model, LOH and NPS together were the strongest predictors for cancer development. These data suggest that QTP could be used to identify lesions that require molecular evaluation and should be integrated with such approaches to facilitate the identification of HMD OPLs at high risk of progression. PMID:18451134

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

    PubMed

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

    2012-06-01

    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.

  11. Malignancy Risk Models for Oral Lesions

    PubMed Central

    Zarate, Ana M.; Brezzo, María M.; Secchi, Dante G.; Barra, José L.

    2013-01-01

    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. PMID:23722122

  12. Characterization of different tissue changes in normal, betel chewers, potentially malignant lesions, conditions and oral squamous cell carcinoma using reflectance confocal microscopy: correlation with routine histopathology.

    PubMed

    Anuthama, Krishnamurthy; Sherlin, Herald J; Anuja, N; Ramani, Pratibha; Premkumar, Priya; Chandrasekar, T

    2010-04-01

    The goal of this study was to characterize the features of normal mucosa, mucosa in betel chewers and smokers, potentially malignant lesions and squamous cell carcinoma of oral mucosa using reflectance confocal microscopy. Oral cavity biopsies were acquired from 25 patients from College of Dental Surgery, Saveetha University who underwent screening for suspected lesions of Oral precancer and Oral cancer along with normal patients who underwent impaction. Biopsies were acquired from the clinically suspicious area and immediately placed in Dulbecco modified eagles growth medium (DMEM). Reflectance confocal images were obtained at multiple image plane depths from biopsies within 6h of excision. After imaging, biopsies were fixed in 10% formalin and submitted for routine histopathological examination by an experienced oral and maxillofacial pathologist. Reflectance confocal images were compared with histological images from the same sample to determine the tissue features which contribute to early cellular changes, image contrast and early diagnosis. The confocal images were obtained to a depth of up to 150 microns on intact biopsy specimens and subsequent 3-dimensional images, keratin thickness measurements, cell measurements, cell density analysis and graphical representations were performed using Leica image analysis software. In normal mucosa keratin deposition were seen as alternating dark and bright stacks and in different cell layers the nuclei were seen as disks of varying intensities. In pre-cancerous lesions the keratin thickness and cell nuclear density were found to be increased when compared to normal controls. In OSMF cases confocal images of fibrosis show scattering from individual fibres as hyperdense areas. Oral squamous cell carcinoma cases demonstrated extensive variations in cell size, nuclear size and nuclear morphology. At cellular level, dysplastic features like increased nuclear density, increased nuclear cytoplasmic ratio, nuclear and cellular

  13. Tuberculosis masquerading as oral malignancy

    PubMed Central

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

    2011-01-01

    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. PMID:22557791

  14. Noninvasive imaging of oral premalignancy and malignancy

    NASA Astrophysics Data System (ADS)

    Wilder-Smith, Petra; Krasieva, T.; Jung, W.; You, J. S.; Chen, Z.; Osann, K.; Tromberg, B.

    2005-04-01

    Objectives: Early detection of cancer and its curable precursors remains the best way to ensure patient survival and quality of life. Despite significant advances in treatment, oral cancer still results in 10,000 U.S. deaths annually, mainly due to the late detection of most oral lesions. Specific aim was to use a combination of non-invasive optical in vivo technologies to test a multi-modality approach to non-invasive diagnostics of oral premalignancy and malignancy. Methods: In the hamster cheek pouch model (120 hamsters), in vivo optical coherence tomography (OCT) and optical Doppler tomography (ODT) mapped epithelial, subepithelial and vascular change throughout carcinogenesis in specific, marked sites. In vivo multi-wavelength multi-photon (MPM) and second harmonic generated (SHG) fluorescence techniques provided parallel data on surface and subsurface tissue structure, specifically collagen presence and structure, cellular presence, and vasculature. Images were diagnosed by 2 blinded, pre-standardized investigators using a standardized scale from 0-6 for all modalities. After sacrifice, histopathological sections were prepared and pathology evaluated on a scale of 0-6. ANOVA techniques compared imaging diagnostics with histopathology. 95% confidence limits of the sensitivity and specificity were established for the diagnostic capability of OCT/ODT+ MPM/SHG using ROC curves and kappa statistics. Results: Imaging data were reproducibly obtained with good accuracy. Carcinogenesis-related structural and vascular changes were clearly visible to tissue depths of 2mm. Sensitivity (OCT/ODT alone: 71-88%; OCT+MPM/SHG: 79-91%) and specificity (OCT alone: 62-83%;OCT+MPM/SHG: 67-90%) compared well with conventional techniques. Conclusions: OCT/ODT and MPM/SHG are promising non-invasive in vivo diagnostic modalities for oral dysplasia and malignancy. Supported by CRFA 30003, CCRP 00-01391V-20235, NIH (LAMMP) RR01192, DOE DE903-91ER 61227, NIH EB-00293 CA91717, NSF BES

  15. Morphometry As a Diagnostic Tool for Potentially Malignant Lesions

    PubMed Central

    Murthy, Sarvani; SR, Ashwinirani; Singh, Sakshi; CP, Athira; Shivaram, Shilpa Kuppareddy; Neethupriya

    2015-01-01

    Introduction Though we are in 21st century with nano technology & tissue printing, there still exist many lacunae in the field of diagnosis. Not much is known about prognostic markers till now from literature to assess potentially malignant lesions. Lesions so called potentially malignant can be termed only after clinical & malignant changes have been developed and there are no means of predicting with certainty the risk of cancerous transformation. Aim Our present study was undertaken to establish the morphometric parameters of the parabasal and spinous cells of normal oral epithelium with the changes occurring in cells of Oral Leukoplakia (OL), Oral Verrucous Carcinoma (OVC) and Oral Squamous Cell Carcinoma (OSCC). Materials and Methods Total 40 patients were divided into Group I which includes patients with normal oral mucosa, group II oral leukoplakia patients, group III oral verrucous carcinoma patients and group IV includes oral squamous cell carcinoma patients. Tissue sections were taken and morphometric analysis of cell area, cell diameter, nuclear area, nuclear diameter, nuclear cytoplasmic ratio was done for parabasal and spinous layer cells. Statistical analysis was done using one-way ANOVA and T-test. Results Nuclear diameter, nuclear area, cell area, nuclear cytoplasmic ratio were significantly increased in OL, OVC, OSCC patients than normal oral mucosa, which was statistically significant. Cell diameter was decreased in OL, OVC, OSCC patients than with normal oral mucosa which was statistically significant. Conclusion Cellular & nuclear parameters showed statistically significant changes in oral leukoplakia, oral verrucous carcinoma & oral squamous cell carcinoma in comparison with normal oral mucosa. PMID:26816987

  16. Survivin expression in oral lichen planus: Role in malignant transformation

    PubMed Central

    Suganya, G; Bavle, Radhika M; Paremala, K; Makarla, Soumya; Sudhakar, M; Reshma, V

    2016-01-01

    Context: Oral lichen planus (OLP) is a potentially malignant disease with a prevalence rate of 0.5–2.2%. It is a T-cell-mediated autoimmune disease, in which cytotoxic CD8+ T-cells trigger apoptosis of the basal cells of oral epithelium. The reported progression of OLP to oral squamous cell carcinoma (OSCC) ranges from 0.4% to 6.5%. Apoptosis plays a major role in the maintenance of tissue homeostasis. The evasion of apoptosis in the form of dysregulation of inhibitors of apoptosis proteins (IAPs) may lead to malignant transformation. Survivin belongs to the second gene family of IAPs, which is overexpressed in many tumors such as OSCC and gastric carcinomas, and its expression is widely involved in apoptosis as well as in tumor metastasis. Materials and Methods: Sections were obtained from the paraffin-embedded archival blocks of patients diagnosed histologically as OLP, and cases with normal epithelium were used for comparison whereas cases with OSCC were used as positive control. Results: We analyzed the expression of survivin in OLP and normal epithelium. Survivin expression with moderate intensity was seen in the cells of basal layer with nuclear positivity in cases of OLP, whereas mild to nil expression was seen in normal epithelium with nuclear and cytoplasmic positivity in different layers. Conclusions: Survivin positivity was seen predominantly in the basal cells of OLP suggesting increased longevity of these cells which in turn might acquire dysplastic changes leading to increased risk of malignant transformation of this premalignant condition. Although the conversion rate may be low, the potential exists in the indolent course of the disease. PMID:27601815

  17. A multicenter study of oral malignant tumors from Thailand

    PubMed Central

    Dhanuthai, Kittipong; Rojanawatsirivej, Somsri; Subarnbhesaj, Ajiravudh; Thosaporn, Watcharaporn; Kintarak, Sompid

    2016-01-01

    Background: Oral malignant tumors in Thailand have not been extensively studied. Hence the following study was conducted. Aims: To determine the prevalence and clinicopathologic data of the oral malignant tumors from Thailand. Subjects and Methods: Biopsy records of the Oral Pathology Department, Chulalongkorn University; Department of Oral Biology and Diagnostic Sciences, Chiang Mai University; Department of Oral Diagnosis, Khon Kaen University and Department of Stomatology, Prince of Songkla University, were reviewed for lesions diagnosed in the category of oral malignant tumors from 2005–2014. Demographic data and site of the lesions were collected. Statistical Analysis Used: Data were analyzed by descriptive statistics using SPSS software version 17.0. Results: Of the 22,639 accessioned cases, 1411 cases (6.23%) were diagnosed as oral malignant tumors. The mean age of the patients was 59.13 ± 17.32 years. A total of 651 cases (46.14%) were diagnosed in males, whereas 759 cases (53.79%) were diagnosed in females. The male-to-female ratio was 0.86:1. The sites of predilection for oral malignant tumors were the gingiva, followed by tongue and alveolar mucosa. The three most common oral malignant tumors in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. Conclusions: This study provides extensive data on the oral malignant tumors from several university biopsy services located in virtually all parts of Thailand. The data from the present study show some similarities with previous studies; however, differences such as gender and site of predilection still exist. PMID:27721612

  18. Malignant hyperpyrexia: successful management following oral surgery.

    PubMed

    Forman, G

    1980-09-01

    Malignant hyperpyrexia (M.H.) is a rare, important and frequently fatal disease provoked by inhalational anaesthetic agents and other drugs. It is manifested most frequently by tachycardia, a rise in core body temperature, muscle stiffness and is associated with profound metabolic effects. It may be transmitted in a predictable familial dominant fashion, but sporadic cases in whom this transference cannot be demonstrated do occur. Susceptibility may be revealed on questioning regarding previous anaesthetic exposure. One such unexpected but successfsully treated case of M.H. is described in detail and the current management and investigation is discussed. PMID:6934802

  19. Application of a Persistent Heparin Treatment Inhibits the Malignant Potential of Oral Squamous Carcinoma Cells Induced by Tumor Cell-Derived Exosomes.

    PubMed

    Sento, Shinya; Sasabe, Eri; Yamamoto, Tetsuya

    2016-01-01

    Exosomes are 30-100 nm-sized membranous vesicles, secreted from a variety of cell types into their surrounding extracellular space. Various exosome components including lipids, proteins, and nucleic acids are transferred to recipient cells and affect their function and activity. Numerous studies have showed that tumor cell-derived exosomes play important roles in tumor growth and progression. However, the effect of exosomes released from oral squamous cell carcinoma (OSCC) into the tumor microenvironment remains unclear. In the present study, we isolated exosomes from OSCC cells and investigated the influence of OSCC cell-derived exosomes on the tumor cell behavior associated with tumor development. We demonstrated that OSCC cell-derived exosomes were taken up by OSCC cells themselves and significantly promoted proliferation, migration, and invasion through the activation of the PI3K/Akt, MAPK/ERK, and JNK-1/2 pathways in vitro. These effects of OSCC cell-derived exosomes were obviously attenuated by treatment with PI3K, ERK-1/2, and JNK-1/2 pharmacological inhibitors. Furthermore, the growth rate of tumor xenografts implanted into nude mice was promoted by treatment with OSCC cell-derived exosomes. The uptake of exosomes by OSCC cells and subsequent tumor progression was abrogated in the presence of heparin. Taken together, these data suggest that OSCC cell-derived exosomes might be a novel therapeutic target and the use of heparin to inhibit the uptake of OSCC-derived exosomes by OSCC cells may be useful for treatment.

  20. Application of a Persistent Heparin Treatment Inhibits the Malignant Potential of Oral Squamous Carcinoma Cells Induced by Tumor Cell-Derived Exosomes

    PubMed Central

    Sento, Shinya; Sasabe, Eri; Yamamoto, Tetsuya

    2016-01-01

    Exosomes are 30–100 nm-sized membranous vesicles, secreted from a variety of cell types into their surrounding extracellular space. Various exosome components including lipids, proteins, and nucleic acids are transferred to recipient cells and affect their function and activity. Numerous studies have showed that tumor cell-derived exosomes play important roles in tumor growth and progression. However, the effect of exosomes released from oral squamous cell carcinoma (OSCC) into the tumor microenvironment remains unclear. In the present study, we isolated exosomes from OSCC cells and investigated the influence of OSCC cell-derived exosomes on the tumor cell behavior associated with tumor development. We demonstrated that OSCC cell-derived exosomes were taken up by OSCC cells themselves and significantly promoted proliferation, migration, and invasion through the activation of the PI3K/Akt, MAPK/ERK, and JNK-1/2 pathways in vitro. These effects of OSCC cell-derived exosomes were obviously attenuated by treatment with PI3K, ERK-1/2, and JNK-1/2 pharmacological inhibitors. Furthermore, the growth rate of tumor xenografts implanted into nude mice was promoted by treatment with OSCC cell-derived exosomes. The uptake of exosomes by OSCC cells and subsequent tumor progression was abrogated in the presence of heparin. Taken together, these data suggest that OSCC cell-derived exosomes might be a novel therapeutic target and the use of heparin to inhibit the uptake of OSCC-derived exosomes by OSCC cells may be useful for treatment. PMID:26849680

  1. Clinical systemic lupeol administration for canine oral malignant melanoma

    PubMed Central

    YOKOE, INORU; AZUMA, KAZUO; HATA, KEISHI; MUKAIYAMA, TOSHIYUKI; GOTO, TAKAHIRO; TSUKA, TAKESHI; IMAGAWA, TOMOHIRO; ITOH, NORIHIKO; MURAHATA, YUSUKE; OSAKI, TOMOHIRO; MINAMI, SABURO; OKAMOTO, YOSHIHARU

    2015-01-01

    Canine oral malignant melanoma (COMM) is the most aggressive malignant tumor in dogs. Lupeol is a triterpene extracted from various fruits and vegetables that reportedly inhibits melanoma cell proliferation in vitro and in vivo. In this study, the efficacy of subcutaneous lupeol for spontaneous COMM was evaluated. A total of 11 dogs (3, 5 and 3 dogs diagnosed with clinical stage I, II and III melanoma, respectively) were evaluated. Subcutaneous lupeol (10 mg/kg) was administered postoperatively at various time points to treat these 11 COMM cases. Of the 11 subjects, 7 exhibited no local recurrence 180 days postoperatively and no severe adverse effects were observed in any of the cases. Furthermore, no distant metastasis was observed during the experimental period. Therefore, systemic lupeol may prevent local tumor progression and distant metastasis and may be a novel adjuvant treatment for the treatment of COMM. PMID:25469276

  2. General Information about Ovarian Low Malignant Potential Tumors

    MedlinePlus

    ... Malignant Potential Tumors Treatment (PDQ®)–Patient Version General Information About Ovarian Low Malignant Potential Tumors Go to ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  3. Non-surgical treatment of canine oral malignant melanoma: A case study of the application of complementary alternative medicine

    PubMed Central

    ITOH, HIROYASU; MUKAIYAMA, TOSHIYUKI; GOTO, TAKAHIRO; HATA, KEISHI; AZUMA, KAZUO; TSUKA, TAKASHI; OSAKI, TOMOHIRO; IMAGAWA, TOMOHIRO; OKAMOTO, YOSHIHARU

    2014-01-01

    This report describes a dog with a clinical stage III oral malignant melanoma that was treated with complementary alternative medicine (CAM). The CAM included high temperature hyperthermia, dendritic cell therapy and lupeol injections. Surgery, radiation and chemotherapy were not performed. Two months after the start of treatment, the tumor disappeared and after six months, the follow-up examinations revealed no recurrence or metastasis of the tumor. Quality of life (QOL) of the dog was maintained; therefore, the application of CAM may be an effective treatment for canine oral malignant melanoma. The effective application of CAM has the potential to prolong life and maintain an excellent QOL for pets. PMID:24932241

  4. Therapeutic Potential of Resveratrol in Lymphoid Malignancies.

    PubMed

    Khan, Omar S; Bhat, Ajaz A; Krishnankutty, Roopesh; Mohammad, Ramzi M; Uddin, Shahab

    2016-01-01

    Natural products have always been sought as a dependable source for the cure of many fatal diseases including cancer. Resveratrol (RSV), a naturally occurring plant polyphenol, has been of recent research interest and is being investigated for its beneficial biological properties that include antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory activities. These effects are mainly mediated by cell cycle arrest, upregulation of proapoptotic proteins, loss of mitochondrial potential, and generation of reactive oxygen species. Among the beneficial properties of RSV, the anticancer property has been of the prime focus and extensively explored during the last few years. Although reports exist on the chemopreventive role of RSV in many solid tumors, limited information is available on the antiproliferative activity of RSV in human lymphoma cells and experimental models. Potential mechanisms for its antiproliferative effect include induction of cell differentiation, apoptosis, and inhibition of DNA synthesis. In this review, the different kinds of lymphoid malignancies and the main mechanisms of cell death induced by resveratrol are discussed. The challenges are limiting in vivo experimental studies involving resveratrol. An attempt for the translation of this compound into a clinical drug also forms a part of this review. PMID:27028800

  5. The effects of "BAR" therapy on oral malignant tumors.

    PubMed

    Nagai, T; Sakaizumi, K; Asanami, S; Lian, S L; Tomita, O; Hirayama, T

    1978-05-01

    "BAR" therapy is a combined therapy with BUdR (Radiosensitizer), Antimetabolites (5-FU, FT-207 etc.) and Radiation for malignant tumours. How radiation can be reduced as far as possible and how the effects of treatment can be increased as much as possible are the objectives of this study of combining radiation and BUdR therapy. The authors attempted to irradiate 3-5 days after the BUdR and antimetabolite had been infused via the superficial temporal artery, in 12 malignant oral tumours (11 squamous cell carcinomas and 1 reticulum-cell sarcoma). BUdR 50-250 mg/day, antimetabolites (5-FU) 10-250 mg/day and a total irradiation dose of 6000 rads by 6 MeV Linac X-ray or Co-60 gamma ray, 200 rads/day were given. 9 marked responses, 2 moderate responses and 1 no response (2 cases were operated on by local resection) were obtained by the authors. Side effects of treatment were observed during the course of "BAR" therapy. Stomatitis was found in all patients and it occurred on the mucosa of the tumour-affected site especially. Dermatitis of the skin of the face was noted in 6 cases, resembling irradiation dermatitis. Fever was observed in 4 cases and it always occurred after irradiation. Diarrhoea was noted in 3 cases and occurred before irradiation, 2 out of 3 were given BUdR 0.1 g and the remaining one was given BUdR 1 g, and 5-FU lg. In addition, there were: 1 loss of appetite, 1 nausea and 1 exfoliation of nails. PMID:353211

  6. Oral bacterial community dynamics in paediatric patients with malignancies in relation to chemotherapy-related oral mucositis: a prospective study

    PubMed Central

    Ye, Y; Carlsson, G; Agholme, M Barr; Wilson, J A L; Roos, A; Henriques-Normark, B; Engstrand, L; Modéer, T; Pütsep, K; Raoult, D

    2013-01-01

    The role of oral bacteria in the development of chemotherapy-related oral mucositis has not been fully elucidated. This study aimed to investigate oral bacterial community diversity and dynamics in paediatric patients with malignancies in relation to the occurrence of oral mucositis. Patients with malignancies (n = 37) and reference individuals without known systemic disorders (n = 38) were recruited. For patients, oral bacterial samples were taken from mucosal surfaces both at the time of malignancy diagnosis and during chemotherapy. If oral mucositis occurred, samples were taken from the surface of the mucositis lesions. Oral mucosal bacterial samples were also taken from reference individuals. All samples were assessed using a 16S ribosomal RNA gene 454 pyrosequencing method. A lower microbial diversity (p < 0.01) and a higher intersubject variability (p < 0.001) were found in patients as compared with reference individuals. At the time of malignancy diagnosis (i.e. before chemotherapy) patients that later developed mucositis showed a higher microbial diversity (p < 0.05) and a higher intersubject variability (p < 0.001) compared with those without mucositis. The change of bacterial composition during chemotherapy was more pronounced in patients who later developed mucositis than those without mucositis (p < 0.01). In conclusion, we found a higher microbial diversity at the time of malignancy diagnosis in patients who later develop oral mucositis and that these patients had a more significant modification of the bacterial community by chemotherapy before the occurrence of mucositis. These findings may possibly be of clinical importance in developing better strategies for personalized preventive management. PMID:23829394

  7. Malignant transformation of oral lichen planus: case report and review of the literature.

    PubMed

    Massa, M C; Greaney, V; Kron, T; Armin, A

    1990-01-01

    Lichen planus is a mucocutaneous disorder well known to both dermatologists and dentists. Traditional belief holds that oral lichen planus predisposes to the development of squamous cell carcinoma of the oral cavity. We present a case that illustrates such a malignant transformation in a patient who smoked and had actinically damaged skin.

  8. Ultrastructural study of benign, low-malignant potential (LMP), and malignant ovarian tumors.

    PubMed

    Ishioka, Shin-ichi; Sagae, Satoru; Ito, Eiki; Kudo, Ryuichi

    2004-03-01

    Ultrastructural characteristics of benign, low-malignant potential (LMP), and malignant ovarian tumors were investigated, considering the aspects of histologic subtypes and histologic grading. In addition, the histogenesis of ovarian cancer was histologically investigated in an attempt to elucidate whether malignant tumor was generated from benign or LMP tumor, or whether it was generated de novo from normal tissues. Although all the benign, LMP, and malignant tumors appeared to be derived from Mullerian duct in serous tumors, the origin of endometrioid or mucinous tumor could not be ultrastructurally clarified. However, there was ultrastructural similarity between benign and malignant tumors among serous, endometrioid, and mucinous tumors, and it was suggested that benign adenoma may be the developmental origin of malignant tumors regardless of the histologic subtype. In addition, the investigation of endometrioid tumors revealed that the differences of histologic grading in malignant tumors reflected the ultrastructural differences, and that G1 tumor had an ultrastructure that was more similar to that of benign and LMP tumors than to that of G2 tumor.

  9. Alcohol metabolism by oral streptococci and interaction with human papillomavirus leads to malignant transformation of oral keratinocytes.

    PubMed

    Tao, Lin; Pavlova, Sylvia I; Gasparovich, Stephen R; Jin, Ling; Schwartz, Joel

    2015-01-01

    Poor oral hygiene, ethanol consumption, and human papillomavirus (HPV) are associated with oral and esophageal cancers. However, the mechanism is not fully known. This study examines alcohol metabolism in Streptococcus and its interaction with HPV-16 in the malignant transformation of oral keratinocytes. The acetaldehyde-producing strain Streptococcus gordonii V2016 was analyzed for adh genes and activities of alcohol and aldehyde dehydrogenases. Streptococcus attachment to immortalized HPV-16 infected human oral keratinocytes, HOK (HPV/HOK-16B), human oral buccal keratinocytes, and foreskin keratinocytes was studied. Acetaldehyde, malondialdehyde, DNA damage, and abnormal proliferation among keratinocytes were also quantified. We found that S. gordonii V2016 expressed three primary alcohol dehydrogenases, AdhA, AdhB, and AdhE, which all oxidize ethanol to acetaldehyde, but their preferred substrates were 1-propanol, 1-butanol, and ethanol, respectively. S. gordonii V2016 did not show a detectable aldehyde dehydrogenase. AdhE is the major alcohol dehydrogenase in S. gordonii. Acetaldehyde and malondialdehyde production from permissible Streptococcus species significantly increased the bacterial attachment to keratinocytes, which was associated with an enhanced expression of furin to facilitate HPV infection and several malignant phenotypes including acetaldehyde adduct formation, abnormal proliferation, and enhanced migration through integrin-coated basement membrane by HPV-infected oral keratinocytes. Therefore, expression of multiple alcohol dehydrogenases with no functional aldehyde dehydrogenase contributes to excessive production of acetaldehyde from ethanol by oral streptococci. Oral Streptococcus species and HPV may cooperate to transform oral keratinocytes after ethanol exposure. These results suggest a significant clinical interaction, but further validation is warranted. PMID:25427911

  10. Alcohol metabolism by oral streptococci and interaction with human papillomavirus leads to malignant transformation of oral keratinocytes.

    PubMed

    Tao, Lin; Pavlova, Sylvia I; Gasparovich, Stephen R; Jin, Ling; Schwartz, Joel

    2015-01-01

    Poor oral hygiene, ethanol consumption, and human papillomavirus (HPV) are associated with oral and esophageal cancers. However, the mechanism is not fully known. This study examines alcohol metabolism in Streptococcus and its interaction with HPV-16 in the malignant transformation of oral keratinocytes. The acetaldehyde-producing strain Streptococcus gordonii V2016 was analyzed for adh genes and activities of alcohol and aldehyde dehydrogenases. Streptococcus attachment to immortalized HPV-16 infected human oral keratinocytes, HOK (HPV/HOK-16B), human oral buccal keratinocytes, and foreskin keratinocytes was studied. Acetaldehyde, malondialdehyde, DNA damage, and abnormal proliferation among keratinocytes were also quantified. We found that S. gordonii V2016 expressed three primary alcohol dehydrogenases, AdhA, AdhB, and AdhE, which all oxidize ethanol to acetaldehyde, but their preferred substrates were 1-propanol, 1-butanol, and ethanol, respectively. S. gordonii V2016 did not show a detectable aldehyde dehydrogenase. AdhE is the major alcohol dehydrogenase in S. gordonii. Acetaldehyde and malondialdehyde production from permissible Streptococcus species significantly increased the bacterial attachment to keratinocytes, which was associated with an enhanced expression of furin to facilitate HPV infection and several malignant phenotypes including acetaldehyde adduct formation, abnormal proliferation, and enhanced migration through integrin-coated basement membrane by HPV-infected oral keratinocytes. Therefore, expression of multiple alcohol dehydrogenases with no functional aldehyde dehydrogenase contributes to excessive production of acetaldehyde from ethanol by oral streptococci. Oral Streptococcus species and HPV may cooperate to transform oral keratinocytes after ethanol exposure. These results suggest a significant clinical interaction, but further validation is warranted.

  11. Spectrally resolved fluorescence lifetime imaging to investigate cell metabolism in malignant and nonmalignant oral mucosa cells

    NASA Astrophysics Data System (ADS)

    Rück, Angelika; Hauser, Carmen; Mosch, Simone; Kalinina, Sviatlana

    2014-09-01

    Fluorescence-guided diagnosis of tumor tissue is in many cases insufficient, because false positive results interfere with the outcome. Improvement through observation of cell metabolism might offer the solution, but needs a detailed understanding of the origin of autofluorescence. With respect to this, spectrally resolved multiphoton fluorescence lifetime imaging was investigated to analyze cell metabolism in metabolic phenotypes of malignant and nonmalignant oral mucosa cells. The time-resolved fluorescence characteristics of NADH were measured in cells of different origins. The fluorescence lifetime of bound and free NADH was calculated from biexponential fitting of the fluorescence intensity decay within different spectral regions. The mean lifetime was increased from nonmalignant oral mucosa cells to different squamous carcinoma cells, where the most aggressive cells showed the longest lifetime. In correlation with reports in the literature, the total amount of NADH seemed to be less for the carcinoma cells and the ratio of free/bound NADH was decreased from nonmalignant to squamous carcinoma cells. Moreover for squamous carcinoma cells a high concentration of bound NADH was found in cytoplasmic organelles (mainly mitochondria). This all together indicates that oxidative phosphorylation and a high redox potential play an important role in the energy metabolism of these cells.

  12. PTHrP promotes malignancy of human oral cancer cell downstream of the EGFR signaling

    SciTech Connect

    Yamada, Tamaki; Tsuda, Masumi; Ohba, Yusuke Kawaguchi, Hideaki; Totsuka, Yasunori; Shindoh, Masanobu

    2008-04-11

    Parathyroid hormone-related protein (PTHrP) is detected in many aggressive tumors and involved in malignant conversion; however, the underlying mechanism remains obscure. Here, we identified PTHrP as a mediator of epidermal growth factor receptor (EGFR) signaling to promote the malignancies of oral cancers. PTHrP mRNA was abundantly expressed in most of the quiescent oral cancer cells, and was significantly upregulated by EGF stimulation via ERK and p38 MAPK. PTHrP silencing by RNA interference, as well as EGFR inhibitor AG1478 treatment, significantly suppressed cell proliferation, migration, and invasiveness. Furthermore, combined treatment of AG1478 and PTHrP knockdown achieved synergistic inhibition of malignant phenotypes. Recombinant PTHrP substantially promoted cell motility, and rescued the inhibition by PTHrP knockdown, suggesting the paracrine/autocrine function of PTHrP. These data indicate that PTHrP contributes to the malignancy of oral cancers downstream of EGFR signaling, and may thus provide a therapeutic target for oral cancer.

  13. Tobacco use, Body Mass Index, and Potentially Malignant Disorders Among petrol fillers in Pimpri-Pune (India): A descriptive study

    PubMed Central

    Reddy, Mamatha G. S.; Kakodkar, Pradnya V.; Singh, Akanksha

    2014-01-01

    Background: Since petrol is combustible and smoking is banned at the petrol pumps, it may be predicted that use of smokeless tobacco is more prevalent among the petrol fillers. Also, smokeless tobacco is a major risk factor for developing oral potentially malignant disorders. The present study was conducted to determine the tobacco use, body mass index (BMI), and potentially malignant disorders among a cohort of petrol fillers and also to evaluate the interaction of tobacco use and BMI with the presence of potentially malignant disorders. Settings and Design: The study was conducted at 45 petrol stations located at Pimpri-Pune, India. A descriptive study design was used. Materials and Method: Four hundred and ten petrol fillers aged 17-64 years participated in the study. General information and tobacco history was obtained by interview. Height and weight were recorded to obtain BMI. Oral examination was conducted to identify the potentially malignant disorders. Statistical analysis: Chi-square test, Z test, and logistic regression were used. The level of significance was fixed at 5%. Results and Conclusions: It was found that 242 (59.02%) used tobacco in different forms. 77.68% were tobacco chewers, and 8.26% were smokers. Leukoplakia was prevalent among 68.47%, oral submucous fibrosis among 27.45%, and 5.08% had erythroplakia. Age (χ2 = 11.46, P < 0.05), duration (χ2 = 17.46, P < 0.05), and frequency of tobacco chewing (χ2 = 14.16, P < 0.05) were significantly associated with potentially malignant disorders. Tobacco chewing was more prevalent as compared to smoking. It can be concluded that the petrol fillers are at a high risk for developing oral potentially malignant disorders. PMID:25422802

  14. Application of cytology and molecular biology in diagnosing premalignant or malignant oral lesions

    PubMed Central

    Mehrotra, Ravi; Gupta, Anurag; Singh, Mamta; Ibrahim, Rahela

    2006-01-01

    Early detection of a premalignant or cancerous oral lesion promises to improve the survival and the morbidity of patients suffering from these conditions. Cytological study of oral cells is a non-aggressive technique that is well accepted by the patient, and is therefore an attractive option for the early diagnosis of oral cancer, including epithelial atypia and squamous cell carcinoma. However its usage has been limited so far due to poor sensitivity and specificity in diagnosing oral malignancies. Lately it has re-emerged due to improved methods and it's application in oral precancer and cancer as a diagnostic and predictive method as well as for monitoring patients. Newer diagnostic techniques such as "brush biopsy" and molecular studies have been developed. Recent advances in cytological techniques and novel aspects of applications of scraped or exfoliative cytology for detecting these lesions and predicting their progression or recurrence are reviewed here. PMID:16556320

  15. Primary malignant melanoma of oral cavity: A tertiary care center experience

    PubMed Central

    Kumar, Vijay; Vishnoi, Jeewan Ram; Kori, Channabasappa G.; Gupta, Sameer; Misra, Sanjeev; Akhtar, Naseem

    2015-01-01

    Background: Primary mucosal malignant melanoma is an extremely rare, aggressive neoplasm accounting for 0.5% of all oral malignancies. Any pigmented lesion in oral cavity should have an index of suspicion, which should be investigated to detect the disease at an early stage and managed appropriately. Melanomas tend to invade locally into the tissue or metastasize more commonly than other malignant tumors of the oral cavity. Materials and Methods: We report a retrospective case series of eight patients suffering from primary oral malignant melanoma treated in our department between 2012 and 2014. The details were recorded from the departmental computerized database and patients on follow-up. Results: There were six male and two female patients with a mean age of 46.8 years. Hard palate was the most common affected site in oral cavity. Pigmented lesion\\ulcer was the most common presenting symptom. Majority of patients (5 patients) were diagnosed with Stage III (distant metastasis), two patients in Stage II, and one patient in Stage I. Three patients were treated with definitive surgery and five patients with palliative chemotherapy in view of distant disease. Following surgery, two of them required adjuvant chemoradiotherapy in view of nodal spread. Patients had a mean follow-up of 10.5 months (range: 8–26 months). Patients treated with definitive surgery had a mean survival rate of 16 months (range: 10–26 months), with local recurrence in one patient. Metastatic melanoma patients treated with palliative chemotherapy had a mean disease control rate of 5 months (range 5–9 months). Conclusion: Oral melanoma carries dismal prognosis with a 5-year survival rate of 5–20%. Early detection of the lesion, proper evaluation, and appropriate treatment are very important to cure the disease. PMID:27390490

  16. Tissue binding patterns of lectins in premalignant and malignant lesions of the oral cavity.

    PubMed

    Vijayan, K K; Remani, P; Beevi, V M; Ankathil, R; Vijayakumar, T; Rajendran, R; Augustine, J; Vasudevan, D M

    1987-01-01

    Lectins from the seeds of Jackfruit (Artocarpus integrifolia) and winged bean (Psophocarpus tetragonolobus) were isolated using an immobilized N-acetyl D-galactosamine column and conjugated to type VI horse radish peroxidase. The purified conjugate was used for the study of tissue specificities using diaminobenzidine as the substrate on dewaxed tissue sections of normal, oral leukoplakia, oral submucous fibrosis, verucous carcinoma and squamous cell carcinoma of the oral cavity. In spite of having a common inhibitory sugar, winged bean lectin did not bind to any lectins whereas Jackfruit lectin showed varying degrees of binding towards the above tissues. The difference in the nature and intensity of binding of the Jackfruit lectin suggest the utilizing this lectin in the differential diagnosis of the premalignant and malignant lesions of the oral cavity.

  17. Malignant Potential of Gastrointestinal Cancers Assessed by Structural Equation Modeling

    PubMed Central

    Onodera, Kei; Takahashi, Hiroaki; Okahara, Satoshi; Kodaira, Junichi; Oohashi, Hirokazu; Isshiki, Hiroyuki; Kawakami, Kentaro; Yamashita, Kentaro; Shinomura, Yasuhisa; Hosokawa, Masao

    2016-01-01

    Background Parameters reported in pathologic reviews have been failing to assess exactly the malignant potential of gastrointestinal cancers. We hypothesized that malignant potential could be defined by common latent variables (hypothesis I), but there are substantial differences in the associations between malignant potential and pathologic parameters according to the origin of gastrointestinal cancers (hypothesis II). We shed light on these issues by structural equation modeling. Materials and Methods We conducted a cross-sectional survey of 217 esophageal, 192 gastric, and 175 colorectal cancer patients who consecutively underwent curative surgery for their pathologic stage I cancers at Keiyukai Sapporo Hospital. Latent variables identified by factor analysis and seven conventional pathologic parameters were introduced in the structural equation modeling analysis. Results Because latent variables were disparate except for their number, 'three' in the examined gastrointestinal cancers, the first hypothesis was rejected. Because configural invariance across gastrointestinal cancers was not approved, the second hypothesis was verified. We could trace the three significant paths on the causal graph from latent variables to lymph node metastasis, which were mediated through depth, lymphatic invasion, and matrilysin expression in esophageal cancer, whereas only one significant path could be traced in both gastric and colorectal cancer. Two of the three latent variables were exogenous in esophageal cancer, whereas one factor was exogenous in the other gastrointestinal cancers. Cancer stemness promoted viability in esophageal cancer, but it was suppressed in others. Conclusion These results reflect the malignant potential of esophageal cancer is higher than that of the other gastrointestinal cancers. Such information might contribute to refining clinical treatments for gastrointestinal cancers. PMID:26889682

  18. Flow cytometric analysis of benign and malignant tumors of the oral and maxillofacial region.

    PubMed

    Chen, R B

    1989-06-01

    One hundred eight fresh tissue samples obtained from normal tissues, benign tumors, and malignant tumors of the oral and maxillofacial region were analyzed for nuclear DNA content and cell kinetics by flow cytometric analysis (FCM). Mean DNA indices for 22 normal tissues and 18 benign tumors were 1.00 and 1.02, respectively, and all samples but one showed diploid pattern. On the other hand, the value for 68 malignant tumors was 1.38, and 66% of them showed an aneuploid pattern. The S phase and G2 + M phase cell populations for malignant tumors were 17.2% and 7.0%, respectively. With the exception of G2 + M phase cell population, all values for malignant tumors were significantly higher than those of normal tissue and benign tumors. Although statistical differences were not observed in most of the values, they were higher in squamous cell carcinomas than in malignant salivary gland tumors. The incidence of aneuploidy and DNA index showed a tendency to increase with the increase of T classification, in N2 and N3 tumors, and in the group of patients with recurrence or who died. The DNA index and the type of DNA ploidy were well correlated to malignancy grade determined by six histologic parameters, whereas the S phase cell population was correlated to mitosis. The analysis by the two-dimensional diagnostic supporting system showed that more than 80% of malignant tumors can be correctly diagnosed by combined values of DNA index and S phase cell population. The results indicate that nuclear DNA analysis by FCM is quite useful as a supplement to histologic diagnosis and evaluation of malignancy grade.

  19. Malignant hyperpyrexia in oral surgery--case report and literature review.

    PubMed

    Monaghan, A; Hindle, I

    1994-06-01

    A case of malignant hyperpyrexia (MH) occurring in a patient undergoing orthognathic surgery is reported which resulted in the procedure being abandoned prior to completion. The oral surgeon's role in recognising the early clinical signs of masseteric spasm and central cyanosis is highlighted. The case shows that with proper investigation and management the MH susceptible patient was able to have a second anaesthetic with safety to complete the surgery. PMID:8068595

  20. Apoptotic Index and Proliferative Index in Premalignant and Malignant Squamous Cell Lesions of the Oral Cavity

    PubMed Central

    Viswanathan, Vidya; Juluri, Ravichandra; Goel, Seema; Madan, Jyotsna; Mitra, Subir K; Gopalakrishnan, Dharmarajan

    2015-01-01

    Background: Oral squamous cell lesions are most commonly diagnosed lesions in India. Both premalignant and malignant lesions are frequently encountered. In this study, we evaluated the role and significance of apoptotic indices (AI) and proliferative indices (PI) in premalignant and malignant squamous cell lesions of the oral cavity. Materials and Methods: A total of 62 histologically proven cases of premalignant and malignant oral squamous cell lesions were analyzed. The biopsies were stained with hematoxylin and eosin and also with monoclonal antibody Ki-67. AI and PI were assessed using a light microscope. Results: AI was found to increase gradually from normal to dysplasia to carcinoma. The highest AI was seen in well-differentiated squamous cell carcinomas (SCCs). PI also was found to increase significantly from normal to dysplasia to carcinoma. The highest PI was seen in poorly differentiated SCC. Conclusion: AI in conjunction with the PI offers an accurate idea as to the nature and course of the lesion and may help to plan timely surgical intervention that results in better clinical prognosis and outcome. PMID:25709366

  1. Therapeutic radiation and the potential risk of second malignancies.

    PubMed

    Kamran, Sophia C; Berrington de Gonzalez, Amy; Ng, Andrea; Haas-Kogan, Daphne; Viswanathan, Akila N

    2016-06-15

    Radiation has long been associated with carcinogenesis. Nevertheless, it is an important part of multimodality therapy for many malignancies. It is critical to assess the risk of secondary malignant neoplasms (SMNs) after radiation treatment. The authors reviewed the literature with a focus on radiation and associated SMNs for primary hematologic, breast, gynecologic, and pediatric tumors. Radiation appeared to increase the risk of SMN in all of these; however, this risk was found to be associated with age, hormonal influences, chemotherapy use, environmental influences, genetic predisposition, infection, and immunosuppression. The risk also appears to be altered with modern radiotherapy techniques. Practitioners of all specialties who treat cancer survivors in follow-up should be aware of this potential risk. Cancer 2016;122:1809-21. © 2016 American Cancer Society.

  2. Therapeutic radiation and the potential risk of second malignancies.

    PubMed

    Kamran, Sophia C; Berrington de Gonzalez, Amy; Ng, Andrea; Haas-Kogan, Daphne; Viswanathan, Akila N

    2016-06-15

    Radiation has long been associated with carcinogenesis. Nevertheless, it is an important part of multimodality therapy for many malignancies. It is critical to assess the risk of secondary malignant neoplasms (SMNs) after radiation treatment. The authors reviewed the literature with a focus on radiation and associated SMNs for primary hematologic, breast, gynecologic, and pediatric tumors. Radiation appeared to increase the risk of SMN in all of these; however, this risk was found to be associated with age, hormonal influences, chemotherapy use, environmental influences, genetic predisposition, infection, and immunosuppression. The risk also appears to be altered with modern radiotherapy techniques. Practitioners of all specialties who treat cancer survivors in follow-up should be aware of this potential risk. Cancer 2016;122:1809-21. © 2016 American Cancer Society. PMID:26950597

  3. Prognostic potential of AgNORs in oral submucous fibrosis

    PubMed Central

    Murgod, Sanjay; Channabasaviah, Girish Hemadal; Shivamurthy, Dyamenahalli Malleshappa; Ashok, Lingappa; Krishnappa, Savita Jangal

    2016-01-01

    Aim and Objective: The role of prognosis cannot be stressed enough, especially when it comes to potentially malignant lesions. The argyrophilic nucleolar organizer regions (AgNORs), which is simple and cost-effective has been used in diagnostic and prognostic pathologies. This study seeks to identify the nucleolar organizer regions (NORs) in oral submucous fibrosis (OSMF), to correlate the AgNOR count with the histologic grade of OSMF, and to evaluate the prognostic potential of AgNOR. Materials and Methods: The sample size consisted of archival paraffin blocks of 35 cases of varying grades of OSMF and 10 cases of squamous cell carcinoma. Normal mucosa samples served as controls for the study. AgNOR staining in accordance with the method of Smith and Crocker was performed and Student's t-test was used for statistical analysis. Results: The results showed an increase in AgNOR counts with corresponding grades of OSMF, the count being least in normal mucosa and also an increase in AgNOR count with corresponding decrease in differentiation of oral squamous cell carcinoma. Conclusion: AgNOR staining is a rapid and inexpensive procedure representing cellular proliferation that can be used to assess the nature of the lesion and therefore, the prognosis. PMID:27114958

  4. HPV and oral lesions: preventive possibilities, vaccines and early diagnosis of malignant lesions.

    PubMed

    Testi, D; Nardone, M; Melone, P; Cardelli, P; Ottria, L; Arcuri, C

    2015-01-01

    The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%-90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before "sexual puberty". The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer.

  5. HPV and oral lesions: preventive possibilities, vaccines and early diagnosis of malignant lesions.

    PubMed

    Testi, D; Nardone, M; Melone, P; Cardelli, P; Ottria, L; Arcuri, C

    2015-01-01

    The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%-90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before "sexual puberty". The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer. PMID:27555904

  6. HPV and oral lesions: preventive possibilities, vaccines and early diagnosis of malignant lesions

    PubMed Central

    TESTI, D.; NARDONE, M.; MELONE, P.; CARDELLI, P.; OTTRIA, L.; ARCURI, C.

    2015-01-01

    SUMMARY The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%–90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before “sexual puberty”. The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer. PMID:27555904

  7. Oral Malignant Melanoma Initially Misdiagnosed as a Racial Pigmentation: A Case Report

    PubMed Central

    Martinelli-Kläy, Carla Patrícia; Laporte, Marcel Leandro; Martinelli, Celso Ricardo; Martinelli, Celso; Lombardi, Tommaso

    2016-01-01

    Oral malignant melanoma (OMM) is rare, representing less than 0.5% of all oral malignancies. The most affected sites are the palate and the maxillary gingiva. Histological examination is important to establish the diagnosis of any suspicious pigmented lesion in the oral cavity, mainly if a precise clinical diagnosis is not possible. We present one case of OMM that was initially diagnosed as a racial pigmentation elsewhere 2 years earlier. Clinical examination showed multiple macules and nodules located on the hard and soft palate, gingiva and superior alveolar mucosa. These lesions were painless and presented a color variation going from dark blue to black. Histological analysis showed sheets and nests of atypical melanocytes displaying a range of shapes such as plasmacytoid, epithelioid, and round cells, located in the superficial corium extending to the deep tissues. A few tumor cells contained variable amounts of melanin. There was no invasion of blood vessels or nerve fibers. Immunohistochemical analysis revealed that the neoplastic cells were positive for HMB-45, melan-A, S-100 and negative for AE1/AE3, confirming the diagnosis of melanoma. The Ki-67 labeling index was around 25%. The patient refused any treatment and died 11 months later. PMID:27195264

  8. Solitary fibrous tumor with malignant potential arising in sublingual gland.

    PubMed

    Ogawa, Ikuko; Sato, Sunao; Kudo, Yasusei; Miyauchi, Mutsumi; Sugiyama, Masaru; Suei, Yoshikazu; Takata, Takashi

    2003-01-01

    A rare case is described of a solitary fibrous tumor (SFT) with malignant potential arising in the sublingual gland. A 59-year-old man presented with a 4-month history of a slowly enlarging painless mass in the center of the floor of the mouth. The tumor was a well-demarcated, firm mass with a multicystic lesion. The tumor exhibited highly cellular areas of spindle cells with patternless architecture alternating with hypocellular areas. The tumor cells were positive for CD34 and bcl-2 as well as vimentin, and negative for epithelial, myogenic, neurogenic and histiocytic markers. The tumor cells formed multiple satellite nodules around dilated ducts in the multicystic lesion, indicating infiltrative growth. In addition, areas exhibiting higher cellularity with increased mitoses were noticed in the satellite nodules, although cellular atypia was not obvious. These findings led to a final diagnosis of SFT with malignant potential. There has been no recurrence or metastasis for 27 months after the surgery. Solitary fibrous tumor of the salivary gland must be differentiated from various spindle cell neoplasms including myogenic, peripheral nerve sheath, fibroblastic and fibro-histiocytic spindle cell neoplasms, hemangiopericytoma and myoepithelioma. In addition to characteristic morphological features, an immunohistochemical positivity for CD34 and bcl-2 may aid in the diagnosis of SFT.

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

    SciTech Connect

    Kakizawa, Hideaki Toyota, Naoyuki; Naito, Akira; Ito, Katsuhide

    2005-12-15

    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.

  10. Photodynamic therapy in the treatment of epithelial potentially malignant disorders of the mouth: advantages and disadvantages

    NASA Astrophysics Data System (ADS)

    Gaimari, G.; Russo, C.; Palaia, G.; Tenore, G.; Del Vecchio, A.; Romeo, U.

    2016-03-01

    Introduction: Leukoplakia is a potentially malignant epithelial lesion with carcinomatous percentages transformation comprehended between 1% and 7% for the homogeneous forms and from 4% to 15% for the non-homogeneous ones. Their removal can be performed by scalpel or laser surgery (excision or vaporization). Photodynamic therapy (PDT) is a bloodless treatment option, based on the involvement of three elements: light, photosensitizer and oxygen. When the molecules of the photosensitizer are activated by a low power laser, energy is transferred to molecular oxygen creating highly reactive radicals of oxygen, that have a cytotoxic effect on target cells. Aim of the study: According to several studies in Literature, it has been decided to evaluate through an initial clinical trial, the efficacy of PDT using topical aminolevulinic acid (5-ALA) activated by a laser diode (λ = 635 nm) to treat potentially oral malignant lesions and to illustrate the advantages and disadvantages derived from the use of this technique. Materials and Methods: Five patients, affected by oral leukoplakia (OL) and oral verrucous leukoplakia (OVL) on the mucosal cheeks, labial commissure, fornix and retromolar areas, have been treated using the PDT. Irradiation time with Diode laser: 1000s. Irradiation mode: Scanning. 5 cycles of 3 minute + final cycle of 100 seconds. Each cycle has been interrupted by pauses of 3 minutes. Results and conclusion: PDT results to be effective in the treatment of OL, especially on OVL. In fact, OVL, due to its irregularity, has got an area of increased retention for the gel that is more difficult to be removed by salivary flow. This could explain the better results obtained in this case rather than in those ones of OL. Furthermore, the advantages have been represented by: less invasivity, high sensitivity for altered tissues, minimal scar tissue, less side effects and no pain during and after operation. In contrast to this, the disadvantages were: longer treatment

  11. Malignant hyperthermia in the oral and maxillofacial surgery patient: an update.

    PubMed

    Patil, Pavan Manohar

    2011-09-01

    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, the depolarizing muscle relaxant succinylcholine, and, rarely in humans, to stresses, such as vigorous exercise and heat. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH provides the clinical diagnostic clues. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Dantrolene sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered. The prevention and treatment of acute episodes of this disorder is of paramount importance to the oral and maxillofacial surgeon. The management of such patients in the oral and maxillofacial surgery setting and the recent advances in the field of MH are presented. PMID:21827956

  12. Notch signaling: its roles and therapeutic potential in hematological malignancies

    PubMed Central

    Gu, Yisu

    2016-01-01

    Notch is a highly conserved signaling system that allows neighboring cells to communicate, thereby controlling their differentiation, proliferation and apoptosis, with the outcome of its activation being highly dependent on signal strength and cell type. As such, there is growing evidence that disturbances in physiological Notch signaling contribute to cancer development and growth through various mechanisms. Notch was first reported to contribute to tumorigenesis in the early 90s, through identification of the involvement of the Notch1 gene in the chromosomal translocation t(7;9)(q34;q34.3), found in a small subset of T-cell acute lymphoblastic leukemia. Since then, Notch mutations and aberrant Notch signaling have been reported in numerous other precursor and mature hematological malignancies, of both myeloid and lymphoid origin, as well as many epithelial tumor types. Of note, Notch has been reported to have both oncogenic and tumor suppressor roles, dependent on the cancer cell type. In this review, we will first give a general description of the Notch signaling pathway, and its physiologic role in hematopoiesis. Next, we will review the role of aberrant Notch signaling in several hematological malignancies. Finally, we will discuss current and potential future therapeutic approaches targeting this pathway. PMID:26934331

  13. The domino effect: Role of hypoxia in malignant transformation of oral submucous fibrosis

    PubMed Central

    Chaudhary, Minal; Bajaj, Shree; Bohra, Shruti; Swastika, Nisu; Hande, Alka

    2015-01-01

    Introduction: Oral submucous fibrosis (OSMF) is a precancerous condition predominantly seen in people of Asian descent. About 7–12% OSMF patients develop oral squamous cell carcinoma (OSCC). Morphological features of OSMF especially fibrosis suggests a possibility of the hypoxic environment in diseased tissues. Oral cancer usually develops from hyperplasia through dysplasia to carcinoma. Neovascularization and increased glycolysis, represent adaptations to a hypoxic microenvironment that are correlated with tumor invasion and metastasis. The adaptation of cells to hypoxia appears to be mediated via hypoxia inducible factor-1α (HIF-1α). HIF-1α is said to be associated with malignant transformation of epithelium in other sites. It appears that HIF-1α plays a significant role in both prostate and cervical carcinogenesis at early stages. We hypothesize that progression of OSMF and malignant transformation in the background of fibrosis mediates via HIF-1α either by up- or down-regulation of various such molecules. Therefore, the main objective of this study was to investigate the relationship between the expression of HIF-1α in OSMF, OSCC and OSCC with OSMF. Aim: To investigate the relationship between the expression of HIF-1α in OSMF, OSCC and OSCC with OSMF. Materials and Methods: The study group consists of histopathologically diagnosed 20 cases of OSCC, oral submucous fibrosis and OSCC with OSMF each. The immunohistochemistry was carried out on neutral buffered formalin-fixed paraffin-embedded tissue sections by using the monoclonal antibody of HIF-1α. Results: A rise in the expression of HIF-1α from OSMF to OSCC to OSCC with OSMF is observed. PMID:26604484

  14. Role of inflammation in oral carcinogenesis (Part I): Histological grading of malignancy using a binary system

    PubMed Central

    PIVA, MARTA RABELLO; DE SOUZA, LÉLIA BATISTA; MARTINS-FILHO, PAULO RICARDO SAQUETE; SOARES, ROSILENE CALAZANS; DE SANTANA SANTOS, THIAGO; DE SOUZA ANDRADE, EMANUEL SÁVIO

    2011-01-01

    The aim of the present study was to assess the suppressant role of the inflammatory infiltrate in oral carcinogenesis through the immunohistochemical expression of CD8 and FOXP3 and to discuss how representative this expression proved, as well as other parameters considered to be of prognostic value. A total of 20 cases of oral epithelial dysplasia and 40 cases of oral squamous cell carcinoma were selected. The criteria suggested by the World Health Organization were used for the histological grading of dysplasia. For carcinoma, a binary method was developed for the present study using parameters such as type of invasion, maturity, presence of epithelial masses and dysmorphism of the masses. Immunohistochemical analysis was performed for assessment of the expression of anti-CD8 and anti-FOXP3 in cases of dysplasia and carcinoma. Although the inflammatory infiltrate was more intense in the majority of carcinomas, it exercised a protective role in the dysplasia cases, as CD8 expression was significantly greater. Although a correlation was found between CD8 and the intensity of the inflammatory infiltrate in the carcinoma cases, CD8 demonstrated >5% expression in only 32.5% of the cases, compared to 80% of the dysplasia cases. Thus, we suggest that the inflammatory infiltrate should not be used as a parameter in routine examinations, as it plays different roles in the various stages of carcinogenesis. The histological grading system for malignancy employed in the present study is indicated for the assessment of oral squamous cell carcinoma. PMID:22848292

  15. Oral malignant melanoma: An aggressive clinical entity - Report of a rare case with review of literature.

    PubMed

    Hasan, Shamimul; Jamdar, Sami Faisal; Jangra, Jogender; Al Beaiji, Sadun Mohammad Al Ageel

    2016-01-01

    Melanomais one of the most dreaded and aggressive neoplasms, being derived from epidermal melanocytes. The majority of melanomas are seen to involve the skin, and primary mucosal melanomas account for less than 1% of all melanomas. Oral malignant melanomas (OMM) are asymptomatic at the initial presentation, but later they become painful with growth and expansion. In the late stages, the patient may present with ulceration, bleeding, tooth mobility, paresthesia, ill-fitting prosthesis, and delayed healing of the extraction sockets. Diagnosis is often delayed due to asymptomatic clinical presentation, with silent progression of the lesion. OMM are associated with poor prognosis due to their invasive and metastasizing tendencies. The condition has poor survival rates, and metastatic melanomas show even worse prognosis. The 5-year survival rate for OMM ranges 4.5-29%, with 18.5 months being the mean survival rate. The tumor is best managed by wide surgical resection; however, consideration should also be made for adjunctive therapies such as chemotherapy, immunotherapy, and radiotherapy. Recurrences may be seen even 10-15 years after the primary therapy. This paper aims to present an interesting report of aggressive OMM in a 50-year-old male patient and emphasizes the role of dental professionals in maintaining a high degree of vigilance for the pigmented lesions of the oral cavity. Pigmented lesions of uncertain origin should be routinely biopsied to rule out malignancy. Early diagnosis of this dreadful entity entails thorough history taking, physical examination, and radiographic features coupled with histopathology. PMID:27114959

  16. Oral malignant melanoma: An aggressive clinical entity - Report of a rare case with review of literature

    PubMed Central

    Hasan, Shamimul; Jamdar, Sami Faisal; Jangra, Jogender; Al Beaiji, Sadun Mohammad Al Ageel

    2016-01-01

    Melanomais one of the most dreaded and aggressive neoplasms, being derived from epidermal melanocytes. The majority of melanomas are seen to involve the skin, and primary mucosal melanomas account for less than 1% of all melanomas. Oral malignant melanomas (OMM) are asymptomatic at the initial presentation, but later they become painful with growth and expansion. In the late stages, the patient may present with ulceration, bleeding, tooth mobility, paresthesia, ill-fitting prosthesis, and delayed healing of the extraction sockets. Diagnosis is often delayed due to asymptomatic clinical presentation, with silent progression of the lesion. OMM are associated with poor prognosis due to their invasive and metastasizing tendencies. The condition has poor survival rates, and metastatic melanomas show even worse prognosis. The 5-year survival rate for OMM ranges 4.5–29%, with 18.5 months being the mean survival rate. The tumor is best managed by wide surgical resection; however, consideration should also be made for adjunctive therapies such as chemotherapy, immunotherapy, and radiotherapy. Recurrences may be seen even 10–15 years after the primary therapy. This paper aims to present an interesting report of aggressive OMM in a 50-year-old male patient and emphasizes the role of dental professionals in maintaining a high degree of vigilance for the pigmented lesions of the oral cavity. Pigmented lesions of uncertain origin should be routinely biopsied to rule out malignancy. Early diagnosis of this dreadful entity entails thorough history taking, physical examination, and radiographic features coupled with histopathology. PMID:27114959

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

    PubMed

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

    2009-06-25

    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.

  18. Acute oral candidiasis during febrile episodes in immunocompromised patients with haematologic malignancies.

    PubMed

    Bergmann, O J; Andersen, P L

    1990-01-01

    To estimate clinical, pathogenic and serological aspects of acute oral candidiasis (AOC) during febril episodes in patients with haematologic malignancies, 23 consecutive patients who developed AOC within 7 days from start of fever were compared with 23 consecutive patients who did not develop AOC. The duration of fever and severe granulocytopenia (less than 0.5 x 10(9)/l) was significantly longer in patients with AOC than in patients without AOC, the median differences between the patients with and without AOC being 4 and 3 days, respectively. Development of AOC could not be correlated to a change in the qualitative composition of the oral microflora. The thrombocyte count was lower in patients with AOC on day 4, whereas no differences were found in leukocyte counts. The prevalences of Candida albicans agglutinin titres greater than or equal to 5 were similar in patients with (24%) and without AOC (33%), and in controls (29%). Seroconversion or a significant increase in the agglutinin titre occurred in 4 patients with AOC and long-lasting fever, who became afebrile after systemic antifungal therapy. It is concluded that AOC is associated with long-lasting fever and decreased bone marrow function as judged by low thrombocyte counts, but not related to specific bacteria in the oral cavity or to an increased occurrence of C. albicans antibodies in the serum.

  19. Malignant rhabdoid tumor of the floor of mouth: first reported case in the oral cavity of an adult.

    PubMed

    Wetzel, Stephanie L; Kerpel, Stanley; Reich, Renee F; Freedman, Paul D

    2015-06-01

    Malignant rhabdoid tumors (MRTs) are exceedingly rare lesions. To our knowledge, only 2 cases have been reported in the oral cavity, with both examples occurring in infants. The current case is the third reported case of MRT of the oral cavity and the first reported case to occur in an adult at this location. The following report describes the clinical, histologic and immunohistochemical features of this tumor.

  20. Expression of keratins in normal, immortalized and malignant oral epithelia in organotypic culture.

    PubMed

    Hansson, A; Bloor, B K; Haig, Y; Morgan, P R; Ekstrand, J; Grafström, R C

    2001-07-01

    Keratins have been extensively studied in tissues and cultured keratinocytes but limited information is available on epithelia reconstructed in vitro. The aim of this study was to examine keratin expression in organotypic epithelia with normal (NOK), immortalized (SVpgC2a) and malignant (SqCC/Y1) human buccal cells. Organotypic epithelia were derived from 10 days of culture at the air-liquid interface of collagen gels containing human oral fibroblasts using a standardized serum-free medium. Sections were stained immunohistochemically with selected mono-specific antibodies to a range of keratins. Organotypic epithelia showed sharp differences in keratin expression and distribution. K4/K13, K1/K10, K6/K16 were variably expressed in NOK and SqCC/Y1 but were not detected in SVpgC2a. K5 was expressed in all organotypic epithelia but K14 was absent in SVpgC2a. K7 and K8 showed variable expression while K18 was expressed uniformly in all epithelia. K19 was expressed consistently in NOK and K20 was distributed heterogeneously in SVpgC2a. Overall, organotypic cultures of normal keratinocytes express many of the same keratins as buccal mucosa. Further, the loss of keratins in SVpgC2a and their retention in SqCC/Y1 have several features in common with the respective keratin profile of oral epithelial dysplasia and well-differentiated oral squamous cell carcinoma. Although qualitative and quantitative differences exist compared to keratin expression in vivo, these cell lines in organotypic culture may serve in studies of the multi-step progression of oral cancer.

  1. Altered p53 in microdissected, metachronous, premalignant and malignant oral lesions from the same patients

    PubMed Central

    Li, Y-Q; Pavelic, Z P; Wang, L-J; McDonald, J S; Gleich, L; Munck-Wikland, E; Dacic, S; Danilovic, Z; Pavelic, L J; Wilson, K M; Gluckman, J L; Stambrook, P J

    1995-01-01

    Aims—To determine whether mutant p53 alleles harboured by malignant tumours of the oral cavity were also present in previous premalignant lesions at the same site. Methods—Paraffin embedded tumour specimens along with their premalignant counterparts were analysed for p53 alterations using immunohistochemistry, microdissection, polymerase chain reaction amplification, and DNA sequencing. Results—Malignant lesions from five of eight patients showed overexpression of p53 protein by immunohistochemistry. Upon DNA sequencing, two of these five specimens had p53 mutations. Of the five patients whose cancers showed p53 overexpression by immunohistochemistry, three had previous premalignant lesions that also had immunohistochemically detectable p53 protein. However, DNA sequencing showed that none of these three had mutations in the p53 gene. The remaining five premalignant lesions had no immunohistochemically detectable p53 protein. Conclusions—Some premalignant lesions have increased p53 protein which can be detected by staining with antibody to p53. This staining is not caused by mutations in p53 that are found in subsequent tumours at the same site. Images PMID:16696020

  2. Photodynamic detection in visualisation of cutaneous and oral mucosa premalignant and malignant lesions: two clinical cases

    NASA Astrophysics Data System (ADS)

    Jurczyszyn, Kamil; Ziólkowski, Piotr; Osiecka, Beata; Gerber, Hanna; Dziedzic, Magdalena

    2008-11-01

    Photodynamic diagnosis (PDD) is promising method of visualisation of premalignant and malignant lesions. PDD is consisted of two main agents: special chemical compound which is called photosensitizer and light. Photosensitizer has affinity to fast proliferating cells such as pre- or malignant. During light irradiation (with proper wavelength - corresponding to absorption peak of photosensitizer) photosensitizer gains energy and passes into excited singlet state S1. Returning to basic singlet state Sn, leads to fluorescence. Due to difference between concentration of photosensitizer in lesion and normal tissue it is possible to obtain high contrast image of lesion. Case #1: 53 years old woman with basal cell carcinoma (BCC) in nasal region; 20% delta-aminolevulinic acid as a precursor of photosensitizer on eucerin base was used. Case #2: 57 years old woman with multifocal oral leukoplakia on cheek mucosa and tongue; 2% chlorophyll gel as photosesitizer was used. All photographs were taken in white light without any filter and in blue and UV light with orange filter: in both cases the total area of the lesions appeared to be larger than it has been clinically observed. Thus, the PDD might be helpful in evaluation of margins of surgical excision of such lesions.

  3. Therapeutic potential of TAS-102 in the treatment of gastrointestinal malignancies.

    PubMed

    Peters, Godefridus J

    2015-11-01

    Fluoropyrimidines form the mainstay in treatment of gastrointestinal malignancies. For decades 5-fluorouracil (5FU), was the major fluoropyrimidine. Currently it is usually given in a combination with leucovorin and oxaliplatin, i.e. FOLFOX, or irinotecan, i.e. FOLFIRI, or all three, i.e. FOLFIRINOX, but gradually it has been replaced by oral fluoropyrimidine prodrug formulations, such as tegafur-uracil and S-1 (both contain ftorafur), and capecitabine (Xeloda®). Novel drugs such as the antivascular endothelial growth factor antibody, bevacizumab, and the anti-epidermal growth factor receptor antibody, cetuximab, are often combined with one of these treatment options. However, when resistance emerged, no alternatives were available. TAS-102, a combination of trifluorothymidine and the thymidine phosphorylase inhibitor TPI in a 1:0.5 ratio, is a novel oral formulation, which is active in 5FU-resistant models, both in vitro and in xenograft models. In addition to inhibition of thymidylate synthase, the major mechanism of action of classical fluoropyrimidines, TAS-102's major mechanism of action is incorporation into DNA, thereby causing DNA damage. TAS-102 also follows an alternative activation pathway via thymidine kinase, and is not a substrate for dihydropyrimidine dehydrogenase. All together this explains the efficacy in 5FU-resistant models. In early clinical studies, the twice-daily schedule (5 days on, 2 days rest) for 2 weeks every 4 weeks, led to a significant disease control rate in various malignancies. This schedule showed consistent activity in two randomized trials on fluoropyrimidine refractory colorectal cancer patients, reflected by an increase of 2-3 months in overall survival in the TAS-102 group compared with placebo. Considering the impressive preclinical potential of various combinations TAS-102 has the promise to become an alternative for 5FU-resistant cancer.

  4. Notch Signaling: A Potential Therapeutic Target for Hematologic Malignancies.

    PubMed

    Gao, Lingbao; Yuan, Keyu; Ding, Wei; Lin, Mei

    2016-01-01

    Notch signaling is a well-conserved cell-fate determining factor in embryo development, and the dyregulation of this signaling is frequently observed in many types of cancers, including hematological malignancies. In this review, we briefly describe the Notch signaling pathway, and we primarily focus on the relationship between Notch and hematological malignancies. We also discuss the clinical development of promising agents including γ-secretase inhibitors (GSIs) and monoclonal antibodies (mAbs). Complete response has been observed among patients with T-cell acute lymphoblastic leukemia (T-ALL) when treated with GSIs. Furthermore, a recent study has suggested that targeting Zmiz1, a direct, selective cofactor of Notch1, rather than targeting Notch directly, maybe helpful to reduce the current target-related toxicities. Taken together, we summarize the role of Notch signaling in hematological malignancies and discuss the treatment strategies for these diseases through targeting Notch signaling. PMID:27650987

  5. Aptamers in hematological malignancies and their potential therapeutic implications.

    PubMed

    Ouyang, Wanyan; Yu, Ziqiang; Zhao, Xiaohong; Lu, Shiyun; Wang, Zhi

    2016-10-01

    Aptamers are short DNA/RNA oligonucleotides selected by the process called Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Due to their functional similarity to monoclonal antibodies with some superior characters, such as high specificity and affinity, flexible modification and stability, and lack of toxicity and immunogenicity, they are promising alternative and complementary targeted therapy for hematologic malignancies. The trends in aptamer technology including production, selection, modifications are briefly discussed in this review. The key aspect is to illustrate aptamers against cancer cells in hematologic malignancies especially those that have entered clinical trials. We also discuss some challenges remain in the application of aptamers. PMID:27637356

  6. Interleukin-37 expression and its potential role in oral leukoplakia and oral squamous cell carcinoma

    PubMed Central

    Lin, Lin; Wang, Jiayi; Liu, Dongjuan; Liu, Sai; Xu, Hao; Ji, Ning; Zhou, Min; Zeng, Xin; Zhang, Dunfang; Li, Jing; Chen, Qianming

    2016-01-01

    Interleukin 37 (IL-37) has been reported to play a significant role in innate immune response and to be involved in several kinds of cancers. However, the investigation of association between IL-37 and oral mucosa carcinogenesis hasn't been clearly established. The aim of the study was to assess IL-37 expression and explore its role in oral mucosa carcinogenesis. The expression of IL-37 increased from normal control (NC) to Oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC). Moreover, statistically highly significant difference was present between scores of OLK with and without mild/moderate dysplasia (P < 0.001). In addition, IL-37 expression was lower in OSCC with lymph node metastasis than those without metastasis (P < 0.01). What’s more, overexpression of IL-37 in RAW264.7 cells remarkably reduced the pseudopodia, vacuolization and the expression of IL-6, TNF-α, and IL-1β. Finally, we found IL-37 and its receptor IL-18Rα but not its binding partner IL-18BP have similar tissue location and expression trend in different stages of oral mucosa carcinogenesis. Overall, IL-37 can be used as a biomarker for early oral tumorigenesis and for malignant transformation risk assessment of premalignant lesions. PMID:27225603

  7. Association Study between Novel CYP26 Polymorphisms and the Risk of Betel Quid-Related Malignant Oral Disorders

    PubMed Central

    Chen, Yun-Ju; Shieh, Tien-Yu; Chen, Chun-Ming; Wang, Yen-Yun; Lin, Yueh-Ming; Chien, Pei-Hsuan

    2015-01-01

    BQ chewing may produce significant amounts of reactive oxygen species (ROS), resulting in oral mucosa damage, and ROS may be metabolized by CYP26 families. Because the CYP26 polymorphisms associated with malignant oral disorders are not well known, we conducted an association study on the associations between the single nucleotide polymorphisms (SNP) of CYP26 families and the risks of malignant oral disorders. BQ chewers with the CYP26A1 rs4411227 C/C+C/G genotype and C allele showed an increased risk of oral and pharyngeal cancer (adjusted odds ratio (aOR) = 2.30 and 1.93, respectively). The CYP26B1 rs3768647 G allele may be associated with oral and pharyngeal cancer (aOR = 3.12) and OPMDs (aOR = 2.23). Subjects with the rs9309462 CT genotype and C allele had an increased risk of oral and pharyngeal cancer (aOR = 9.24 and 8.86, respectively) and OPMDs (aOR = 8.17 and 7.87, respectively). The analysis of joint effects between the CYP26A1 rs4411227 and CYP26B1 rs3768647/rs9309462 polymorphisms revealed statistical significance (aOR = 29.91 and 10.03, respectively). Additionally, we observed a significant mRNA expression of CY26A1 and CYP26B1 in cancerous tissues compared with adjacent noncancerous tissues. Our findings suggest that novel CYP26 polymorphisms are associated with an increased risk of malignant oral disorders, particularly among BQ chewers. PMID:25839051

  8. Recognizing and overcoming potential barriers to oral medications for MS.

    PubMed

    Moses, Harold

    2014-10-01

    Three FDA-approved oral medications are available for the treatment of relapsing forms of multiple sclerosis: fingolimod, teriflunomide, and dimethyl fumarate. While injection and IV treatments have proven to be beneficial, these newer oral agents also offer positive outcomes for patients. Numerous barriers exist, though, for these oral agents, including the unknown long-term efficacy and safety and potential side effects. Despite possible side effects, oral agents provide convenience, ease of use, and the elimination of injection/IV administration-site pain. To ensure MS patients receive the most appropriate individualized care, clinicians should present all of the available treatment options to both newly diagnosed and established patients. PMID:25373133

  9. Dose-response relationships of oral habits associated with the risk of oral pre-malignant lesions among men who chew betel quid.

    PubMed

    Yen, Amy Ming-Fang; Chen, Shao-Ching; Chen, Tony Hsiu-Hsi

    2007-08-01

    Betel quid, cigarettes and alcohol are well-recognized risk factors for oral cancer. However, the combined effect of the frequency and duration of these oral habits on the risk for developing oral pre-malignancies among betel quid users has not been fully addressed. In this study, an oral screening programme for men chewing betel quid was carried out by well-trained dentists for early detection of oral pre-malignancy lesions. Using generalized logit model and proportional odds model, we found that, compared with the occasional user, the adjusted odds ratios of developing leukoplakia for men chewing one to 10 pieces of betel quid, 11-20 pieces, and more than 20 pieces per day were estimated as 2.14 (95% confidence interval [CI] 1.62-2.81), 2.99 (95% CI 2.06-4.27), and 5.37 (95% CI 3.76-7.47), respectively. The corresponding figures for erythroleukoplakia were 3.69 (95% CI 1.55-8.79), 13.78 (95% CI 5.76-32.98), and 36.64 (95% CI 15.94-84.16), respectively. Similar results were found while the duration was considered. The dose-response relationships were not as noteworthy for cigarette and alcohol drinking.

  10. Trends in frequency and duration of tobacco habit in relation to potentially malignant lesion: A 3 years retrospective study

    PubMed Central

    Garg, Kavita Nitish; Raj, Vineet; Chandra, Shaleen

    2013-01-01

    Background: Oral cancer is one of the most debilitating and disfiguring of all malignancies; it is one of the most frequently occurring cancers in the body. The high incidence of oral cancer in India has been attributed to widespread tobacco usage among the population either in chewable or smoked form. Aim: In the current study, we retrospectively analyzed 191 cases (2007-2009) of potentially malignant oral lesions, which had been biopsied in our hospital, in order to assess their relationship with tobacco usage. Materials and Methods: Based on the histopathology, these lesions were classified as high-risk lesions (HRL), low-risk lesions, and questionable risk lesions. The data obtained were then analyzed to find out the correlation between the occurrence of risk level with various demographic parameters such as age and gender as well as with type, frequency, and duration of tobacco habit. Results: Out of 191 cases, 122 patients reported with tobacco habit (chewers, smokers, and both) and frequency (<5 and >5 packets/day) were seen in 109 cases and duration (<5 and >5 years) seen in 99 cases. These parameters were correlated with histopathological diagnosis and results showed that both the groups came under the high-risk category. Further analysis of decategorized group (age and gender) was also done. Conclusion: Analysis showed that overall histopathologically diagnosed HRLs were seen more in males and smokers compared to female and chewers, respectively. PMID:24250079

  11. Melanoma cell galectin-1 ligands functionally correlate with malignant potential*

    PubMed Central

    Yazawa, Erika M.; Geddes-Sweeney, Jenna E.; Cedeno-Laurent, Filiberto; Walley, Kempland C.; Barthel, Steven R.; Opperman, Matthew J.; Liang, Jennifer; Lin, Jennifer Y.; Schatton, Tobias; Laga, Alvaro C.; Mihm, Martin C.; Qureshi, Abrar A.; Widlund, Hans R.; Murphy, George F.; Dimitroff, Charles J.

    2015-01-01

    Galectin-1 (Gal-1)-binding to Gal-1 ligands on immune and endothelial cells can influence melanoma development through dampening anti-tumor immune responses and promoting angiogenesis. However, whether Gal-1 ligands are functionally expressed on melanoma cells to help control intrinsic malignant features remains poorly understood. Here, we analyzed expression, identity and function of Gal-1 ligands in melanoma progression. Immunofluorescent analysis of benign and malignant human melanocytic neoplasms revealed that Gal-1 ligands were abundant in severely-dysplastic nevi as well as in primary and metastatic melanomas. Biochemical assessments indicated that melanoma cell adhesion molecule (MCAM) was a major Gal-1 ligand on melanoma cells that was largely dependent on its N-glycans. Other melanoma cell Gal-1 ligand activity conferred by O-glycans was negatively regulated by α2,6 sialyltransferase ST6GalNAc2. In Gal-1-deficient mice, MCAM-silenced (MCAMKD) or ST6GalNAc2-overexpressing (ST6O/E) melanoma cells exhibited slower growth rates, underscoring a key role for melanoma cell Gal-1 ligands and host Gal-1 in melanoma growth. Further analysis of MCAMKD or ST6O/E melanoma cells in cell migration assays indicated that Gal-1 ligand-dependent melanoma cell migration was severely inhibited. These findings provide a refined perspective on Gal-1 – melanoma cell Gal-1 ligand interactions as contributors to melanoma malignancy. PMID:25756799

  12. Clinical Outcomes of Patients with Resected Oral Cavity Cancer and Simultaneous Second Primary Malignancies

    PubMed Central

    Kang, Chung-Jan; Lin, Chien-Yu; Chang, Joseph Tung-Chieh; Tsang, Ngan-Ming; Huang, Bing-Shen; Chao, Yin-Kai; Lee, Li-Yu; Hsueh, Chuen; Wang, Hung-Ming; Liau, Chi-Ting; Hsu, Cheng-Lung; Hsieh, Chia-Hsun; Ng, Shu-Hang; Lin, Chih-Hung; Tsao, Chung-Kan; Fang, Tuan-Jen; Huang, Shiang-Fu; Chang, Kai-Ping; Yen, Tzu-Chen

    2015-01-01

    Objectives Simultaneous second primary tumors (SSPT) are not uncommon in patients with oral cavity squamous cell carcinoma (OSCC) living in areas where the habit of betel quid chewing is widespread. We sought to identify the main prognostic factors in OSCC patients with SSPT and incorporate them into a risk stratification scheme. Methods A total of 1822 consecutive patients with primary OSCC treated between January 1996 and February 2014 were analyzed for the presence of SSPT. The 18-month and 5-year overall survival (OS) rates served as the main outcome measures. Results Of the 1822 patients, 77 (4%) were found to have SSPT (i.e, two malignancies identified within one month of each other). The 18-month and 5-year OS rates in patients without SSPT and with SSPT were 82% and 69%, and 72% and 53%, respectively (p = 0.0063). Patients with SSPT were further divided into patients with either esophageal cancer or hepatocellular carcinoma (eso-HCC subgroup, n = 8) and other tumors (NO eso-HCC subgroup, n = 69). After multivariate analysis, neck nodal extracapsular spread (ECS, n = 18) and the presence of eso-HCC were identified as independent adverse prognostic factors. The 18-month OS rates of SSPT patients with both eso-HCC and ECS (n = 5) vs. the remaining patients (n = 72) were 0% and 78%, respectively (p < 0.0001). Conclusion OSCC patients with neck nodal ECS and esophageal cancer or hepatocellular carcinoma as SSPT have a dismal short-term prognosis. PMID:26335067

  13. A case-control study of the possible association between oral contraceptives and malignant melanoma.

    PubMed Central

    Adam, S. A.; Sheaves, J. K.; Wright, N. H.; Mosser, G.; Harris, R. W.; Vessey, M. P.

    1981-01-01

    In a case-control study, we investigated 169 women aged 15-49 years with malignant melanoma notified to the Oxford and South Western cancer registries during the years 1971-1976, together with 507 matched controls. Data about medical, reproductive, drug and smoking histories were obtained both by reviewing general practitioner (GP) records and from the women themselves by postal questionnaires. There was no significant evidence of any overall increase in the risk of melanoma in oral contraceptive (OC) users (data from GP records-ever use vs never use, relative risk (RR) 1.34, 95% confidence limits 0.92-1.96; corresponding data from postal questionnaires-RR 1.13, limits 0.73-1.75). However, although not significant, the risk estimated from data in the postal questionnaires was higher in women who had used OCs for 5 years or more (use greater than or equal to 5 years vs never use, RR 1.57, limits 0.83-3.03). Previously demonstrated risk factors for melanoma, such as fair skin, blond or red hair and Celtic origin were found to be commoner in the cases than in the controls. Data from the Oxford/Family Planning Association contraceptive study were also examined. Unexpectedly there was a strong suggestion of a negative association between OC use and melanoma risk, but the analysis was based on only 12 women with the disease. PMID:7259960

  14. Uniform expression of alcohol dehydrogenase 3 in epithelia regenerated with cultured normal, immortalised and malignant human oral keratinocytes.

    PubMed

    Hedberg, J J; Hansson, A; Nilsson, J A; Höög, J O; Grafström, R C

    2001-01-01

    The human oral epithelium is a target for damage from the inhalation of formaldehyde. However, most experimental studies on this chemical have relied on laboratory animals that are obligatory nose breathers, including rats and mice. Therefore, in vitro model systems that mimic the structure of the human oral epithelium and which retain normal tissue-specific metabolic competence are desirable. Based on the established role of alcohol dehydrogenase 3 (ADH3), also known as glutathione-dependent formaldehyde dehydrogenase, as the primary enzyme catalysing the detoxification of formaldehyde, the aim of this study was to investigate the expression of ADH3 in organotypic epithelia regenerated with normal (NOK), immortalised (SVpgC2a) and malignant (SqCC/Y1) human oral keratinocytes. Organotypic epithelia, usually consisting of 5-10 cell layers, were produced at the air-liquid interface of collagen gels containing human oral fibroblasts, after culture for 10 days in a standardised serum-free medium. Immunochemical staining demonstrated uniform expression of ADH3 in these organotypic epithelia, as well as in the epithelial cells of oral tissue. The specificity of the ADH3 antiserum was ascertained from the complete neutralisation of the immunochemical reaction with purified ADH3 protein. Assessment of the staining intensities indicated that the expression levels were similar among the regenerated epithelia. Furthermore, the regenerated epithelia showed similar ADH3 expression to the epithelium in oral tissue. Therefore, a tissue-like expression pattern for ADH3 can be generated from the culture of various oral keratinocyte lines in an organotypic state. Similar expression levels among the various cell lines indicate the preservation of ADH3 during malignant transformation, and therefore that NOK, SVpgC2a and SqCC/Y1 represent functional models for in vitro studies of formaldehyde metabolism in human oral mucosa.

  15. Clinical trial analyzing the impact of continuous defocused CO2 laser vaporisation on the malignant transformation of erosive oral lichen planus.

    PubMed

    Mücke, Thomas; Gentz, Irina; Kanatas, Anastasios; Ritschl, Lucas M; Mitchell, David A; Wolff, Klaus-Dietrich; Deppe, Herbert

    2015-10-01

    The erosive oral lichen planus (OLP) represents a management challenge to the clinician and can have debilitating consequences to patients' quality of life. The aims of this work were to determine the incidence of malignant transformation to squamous cell carcinoma (SCC) in patients undergoing traditional symptomatic treatments (oral salve containing lidocaine hydrochloride or systemic diclofenac) compared to patients that were managed with a defocused continuous CO2 laser beam. A total of 171 patients with histologically confirmed erosive OLP were included into this study. After treatment, patients were assessed until completion of wound healing, at least every 3-6 months for the first 2 years, and every 6-12 months thereafter. The study included 87 women (50.9%) and 84 men (49.1%). A total of 103 patients (60.2%) underwent symptomatic conservative treatment, and 68 patients (39.8%) underwent continuous defocused CO2 laser treatments. SCC developed in 16 patients (9.4%), 2 patients (2.9%) after continuous defocused CO2 laser treatment and 14 patients (13.6%) with symptomatic treatment only. This study provides insight into the potential impact of the CO2 laser in the management of patients with erosive OLP and the influence on the recurrence rate of erosive OLP, as well as malignant transformation to oral SCC.

  16. Do Clear Cell Papillary Renal Cell Carcinomas Have Malignant Potential?

    PubMed

    Diolombi, Mairo L; Cheng, Liang; Argani, Pedram; Epstein, Jonathan I

    2015-12-01

    disease. One patient was presumed to have contralateral disease on the basis of imaging findings and is alive and well 37 months after multiple partial nephrectomies. Metastatic disease to the lung was clinically presumed in 1 patient in whom a higher-grade lesion may have been missed during sampling of the predominantly cystic pT1b tumor and tissue confirmation of the metastases was not obtained. Another case presented with multiple skeletal and pulmonary metastases 8 months after resection of pT3 sarcomatoid CCPRCC. The patient with the sarcomatoid RCC died of multifocal skeletal and pulmonary metastatic disease 13 months after resection of the renal tumor. Our study, the largest to date with follow-up, along with others, suggests that pure CCPRCC is an indolent tumor and should be renamed "clear cell papillary neoplasm of low malignant potential" to reflect their biology. PMID:26426379

  17. CD30 is a potential therapeutic target in malignant mesothelioma.

    PubMed

    Dabir, Snehal; Kresak, Adam; Yang, Michael; Fu, Pingfu; Wildey, Gary; Dowlati, Afshin

    2015-03-01

    CD30 is a cytokine receptor belonging to the TNF superfamily (TNFRSF8) that acts as a regulator of apoptosis. The presence of CD30 antigen is important in the diagnosis of Hodgkin disease and anaplastic large cell lymphoma. There have been sporadic reports of CD30 expression in nonlymphoid tumors, including malignant mesothelioma. Given the remarkable success of brentuximab vedotin, an antibody-drug conjugate directed against CD30 antigen, in lymphoid malignancies, we undertook a study to examine the incidence of CD30 in mesothelioma and to investigate the ability to target CD30 antigen in mesothelioma. Mesothelioma tumor specimens (N = 83) were examined for CD30 expression by IHC. Positive CD30 expression was noted in 13 mesothelioma specimens, primarily those of epithelial histology. There was no significant correlation of CD30 positivity with tumor grade, stage, or survival. Examination of four mesothelioma cell lines (H28, H2052, H2452, and 211H) for CD30 expression by both FACS analysis and confocal microscopy showed that CD30 antigen localized to the cell membrane. Brentuximab vedotin treatment of cultured mesothelioma cells produced a dose-dependent decrease in cell growth and viability at clinically relevant concentrations. Our studies validate the presence of CD30 antigen in a subgroup of epithelial-type mesothelioma tumors and indicate that selected mesothelioma patients may derive benefit from brentuximab vedotin treatment.

  18. CD30 is a potential therapeutic target in malignant mesothelioma

    PubMed Central

    Dabir, Snehal; Kresak, Adam; Yang, Michael; Fu, Pingfu; Wildey, Gary; Dowlati, Afshin

    2015-01-01

    CD30 is a cytokine receptor belonging to the tumor necrosis factor superfamily (TNFRSF8) that acts as a regulator of apoptosis. The presence of CD30 antigen is important in the diagnosis of Hodgkin’s disease and anaplastic large cell lymphoma. There have been sporadic reports of CD30 expression in non-lymphoid tumors, including malignant mesothelioma. Given the remarkable success of brentuximab vedotin, an antibody-drug conjugate directed against CD30 antigen, in lymphoid malignancies, we undertook a study to examine the incidence of CD30 in mesothelioma and to investigate the ability to target CD30 antigen in mesothelioma. Mesothelioma tumor specimens (N = 83) were examined for CD30 expression by immunohistochemistry. Positive CD30 expression was noted in 13 mesothelioma specimens, primarily those of epithelial histology. There was no significant correlation of CD30 positivity with either tumor grade, stage or survival. Examination of four mesothelioma cell lines (H28, H2052, H2452, and 211H) for CD30 expression by both FACS analysis and confocal microscopy showed that CD30 antigen localized to the cell membrane. Brentuximab vedotin treatment of cultured mesothelioma cells produced a dose-dependent decrease in cell growth and viability at clinically relevant concentrations. Our studies validate the presence of CD30 antigen in a subgroup of epithelial-type mesothelioma tumors and indicate that selected mesothelioma patients may derive benefit from brentuximab vedotin treatment. PMID:25589494

  19. Bacteriophage and their potential roles in the human oral cavity.

    PubMed

    Edlund, Anna; Santiago-Rodriguez, Tasha M; Boehm, Tobias K; Pride, David T

    2015-01-01

    The human oral cavity provides the perfect portal of entry for viruses and bacteria in the environment to access new hosts. Hence, the oral cavity is one of the most densely populated habitats of the human body containing some 6 billion bacteria and potentially 35 times that many viruses. The role of these viral communities remains unclear; however, many are bacteriophage that may have active roles in shaping the ecology of oral bacterial communities. Other implications for the presence of such vast oral phage communities include accelerating the molecular diversity of their bacterial hosts as both host and phage mutate to gain evolutionary advantages. Additional roles include the acquisitions of new gene functions through lysogenic conversions that may provide selective advantages to host bacteria in response to antibiotics or other types of disturbances, and protection of the human host from invading pathogens by binding to and preventing pathogens from crossing oral mucosal barriers. Recent evidence suggests that phage may be more involved in periodontal diseases than were previously thought, as their compositions in the subgingival crevice in moderate to severe periodontitis are known to be significantly altered. However, it is unclear to what extent they contribute to dysbiosis or the transition of the microbial community into a state promoting oral disease. Bacteriophage communities are distinct in saliva compared to sub- and supragingival areas, suggesting that different oral biogeographic niches have unique phage ecology shaping their bacterial biota. In this review, we summarize what is known about phage communities in the oral cavity, the possible contributions of phage in shaping oral bacterial ecology, and the risks to public health oral phage may pose through their potential to spread antibiotic resistance gene functions to close contacts. PMID:25861745

  20. Bacteriophage and their potential roles in the human oral cavity

    PubMed Central

    Edlund, Anna; Santiago-Rodriguez, Tasha M.; Boehm, Tobias K.; Pride, David T.

    2015-01-01

    The human oral cavity provides the perfect portal of entry for viruses and bacteria in the environment to access new hosts. Hence, the oral cavity is one of the most densely populated habitats of the human body containing some 6 billion bacteria and potentially 35 times that many viruses. The role of these viral communities remains unclear; however, many are bacteriophage that may have active roles in shaping the ecology of oral bacterial communities. Other implications for the presence of such vast oral phage communities include accelerating the molecular diversity of their bacterial hosts as both host and phage mutate to gain evolutionary advantages. Additional roles include the acquisitions of new gene functions through lysogenic conversions that may provide selective advantages to host bacteria in response to antibiotics or other types of disturbances, and protection of the human host from invading pathogens by binding to and preventing pathogens from crossing oral mucosal barriers. Recent evidence suggests that phage may be more involved in periodontal diseases than were previously thought, as their compositions in the subgingival crevice in moderate to severe periodontitis are known to be significantly altered. However, it is unclear to what extent they contribute to dysbiosis or the transition of the microbial community into a state promoting oral disease. Bacteriophage communities are distinct in saliva compared to sub- and supragingival areas, suggesting that different oral biogeographic niches have unique phage ecology shaping their bacterial biota. In this review, we summarize what is known about phage communities in the oral cavity, the possible contributions of phage in shaping oral bacterial ecology, and the risks to public health oral phage may pose through their potential to spread antibiotic resistance gene functions to close contacts. PMID:25861745

  1. Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma.

    PubMed

    Maekawa, Naoya; Konnai, Satoru; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Takagi, Satoshi; Kagawa, Yumiko; Nakajima, Chie; Suzuki, Yasuhiko; Kato, Yukinari; Murata, Shiro; Ohashi, Kazuhiko

    2016-01-01

    Spontaneous cancers are common diseases in dogs. Among these, some malignant cancers such as oral melanoma, osteosarcoma, hemangiosarcoma, and mast cell tumor are often recognized as clinical problems because, despite their high frequencies, current treatments for these cancers may not always achieve satisfying outcomes. The absence of effective systemic therapies against these cancers leads researchers to investigate novel therapeutic modalities, including immunotherapy. Programmed death 1 (PD-1) is a costimulatory receptor with immunosuppressive function. When it binds its ligands, PD-ligand 1 (PD-L1) or PD-L2, PD-1 on T cells negatively regulates activating signals from the T cell receptor, resulting in the inhibition of the effector function of cytotoxic T lymphocytes. Aberrant PD-L1 expression has been reported in many human cancers and is considered an immune escape mechanism for cancers. In clinical trials, anti-PD-1 or anti-PD-L1 antibodies induced tumor regression for several malignancies, including advanced melanoma, non-small cell lung carcinoma, and renal cell carcinoma. In this study, to assess the potential of the PD-1/PD-L1 axis as a novel therapeutic target for canine cancer immunotherapy, immunohistochemical analysis of PD-L1 expression in various malignant cancers of dogs was performed. Here, we show that dog oral melanoma, osteosarcoma, hemangiosarcoma, mast cell tumor, mammary adenocarcinoma, and prostate adenocarcinoma expressed PD-L1, whereas some other types of cancer did not. In addition, PD-1 was highly expressed on tumor-infiltrating lymphocytes obtained from oral melanoma, showing that lymphocytes in this cancer type might have been functionally exhausted. These results strongly encourage the clinical application of PD-1/PD-L1 inhibitors as novel therapeutic agents against these cancers in dogs. PMID:27276060

  2. Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma

    PubMed Central

    Maekawa, Naoya; Konnai, Satoru; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Takagi, Satoshi; Kagawa, Yumiko; Nakajima, Chie; Suzuki, Yasuhiko; Kato, Yukinari; Murata, Shiro; Ohashi, Kazuhiko

    2016-01-01

    Spontaneous cancers are common diseases in dogs. Among these, some malignant cancers such as oral melanoma, osteosarcoma, hemangiosarcoma, and mast cell tumor are often recognized as clinical problems because, despite their high frequencies, current treatments for these cancers may not always achieve satisfying outcomes. The absence of effective systemic therapies against these cancers leads researchers to investigate novel therapeutic modalities, including immunotherapy. Programmed death 1 (PD-1) is a costimulatory receptor with immunosuppressive function. When it binds its ligands, PD-ligand 1 (PD-L1) or PD-L2, PD-1 on T cells negatively regulates activating signals from the T cell receptor, resulting in the inhibition of the effector function of cytotoxic T lymphocytes. Aberrant PD-L1 expression has been reported in many human cancers and is considered an immune escape mechanism for cancers. In clinical trials, anti-PD-1 or anti-PD-L1 antibodies induced tumor regression for several malignancies, including advanced melanoma, non-small cell lung carcinoma, and renal cell carcinoma. In this study, to assess the potential of the PD-1/PD-L1 axis as a novel therapeutic target for canine cancer immunotherapy, immunohistochemical analysis of PD-L1 expression in various malignant cancers of dogs was performed. Here, we show that dog oral melanoma, osteosarcoma, hemangiosarcoma, mast cell tumor, mammary adenocarcinoma, and prostate adenocarcinoma expressed PD-L1, whereas some other types of cancer did not. In addition, PD-1 was highly expressed on tumor-infiltrating lymphocytes obtained from oral melanoma, showing that lymphocytes in this cancer type might have been functionally exhausted. These results strongly encourage the clinical application of PD-1/PD-L1 inhibitors as novel therapeutic agents against these cancers in dogs. PMID:27276060

  3. Current Aspects on Oral Squamous Cell Carcinoma

    PubMed Central

    Markopoulos, Anastasios K

    2012-01-01

    Oral squamous cell carcinoma is the most common malignant epithelial neoplasm affecting the oral cavity. This article overviews the essential points of oral squamous cell carcinoma, highlighting its risk and genomic factors, the potential malignant disorders and the therapeutic approaches. It also emphasizes the importance of the early diagnosis. PMID:22930665

  4. The impact of oral herpes simplex virus infection and candidiasis on chemotherapy-induced oral mucositis among patients with hematological malignancies.

    PubMed

    Chen, Y-K; Hou, H-A; Chow, J-M; Chen, Y-C; Hsueh, P-R; Tien, H-F

    2011-06-01

    The aim of this study was to evaluate the influences of oral candidiasis and herpes simplex virus 1 (HSV-1) infections in chemotherapy-induced oral mucositis (OM). The medical records of 424 consecutive patients with hematological malignancies who had received chemotherapy at a medical center in Taiwan from January 2006 to November 2007 were retrospectively reviewed. The results of swab cultures of fungus and HSV-1 for OM were correlated with associated clinical features. Younger age, myeloid malignancies, and disease status other than complete remission before chemotherapy were significantly correlated with the development of OM. Risks of fever (p < 0.001) and bacteremia were higher in patients with OM. Among 467 episodes of OM with both swab cultures available, 221 were non-infection (47.3%) and 246 were related to either fungal infections, HSV-1 infections, or both (52.7%); of the 246 episodes, 102 were associated with fungal infections alone (21.8%), 98 with HSV-1 infections alone (21%), and 46 with both infections (9.9%). Patients who had received antifungal agents prior to OM occurrence tended to have HSV-1 infection (p < 0.001). Our results suggest that Candida albicans and HSV-1 play an important role in chemotherapy-induced OM in patients with hematological malignancies.

  5. Surgical treatment of potentially primary malignant adrenal tumors: an unresolved issue.

    PubMed

    Zografos, George N; Perysinakis, Iraklis; Kyrodimou, Eustathia; Kassi, Eva; Kaltsas, Gregory

    2015-01-01

    Although the great majority of incidentalomas are adrenocortical adenomas, a number of them, depending on the size and radiological characteristics of the lesions, will turn out to be carcinomas. These tumors may present as suspicious on initial evaluation and potentially malignant or malignant on histology. Adrenocortical carcinoma is a rare and aggressive malignancy with evolving diagnostic and therapeutic approaches. Laparoscopic surgery has become the gold standard for surgery of benign adrenal tumors. Despite the extensive experience gained in laparoscopic adrenalectomy, controversy still remains in the management of adrenal tumors with high suspicion or evidence of malignancy. The aim of this review is to update the existing information regarding the diagnostic approach and surgical management of suspicious and potentially malignant primary adrenal tumors.The interpretation of radiologic characteristics is a cornerstone in pre-operative assessment of large adrenal masses, since open surgery remains the preferred procedure when malignancy is suspected in large tumors with possible local invasion. Despite the improvement of imaging techniques, they lack sufficient accuracy to exclude primary malignancy in tumors from 4 cm to 10 cm in size. An initial laparoscopic approach can be used in this group of patients, but early conversion to open technique is mandatory if curative resection cannot be performed. Adrenal tumors >10 cm of malignant potential should be treated by the open approach from the start. Solitary adrenal metastasis from another primary malignancy is usually amenable to laparoscopic surgery. Patients with suspected adrenal cancer should be referred to tertiary centers that perform laparoscopic and open adrenal surgery with minimal morbidity and mortality.

  6. Oral verrucous carcinoma arising from lichen planus and esophageal squamous cell carcinoma in a patient with hepatitis C virus-related liver cirrhosis-hyperinsulinemia and malignant transformation: A case report.

    PubMed

    Nagao, Yumiko; Sata, Michio

    2013-01-01

    Oral lichen planus (OLP) is a potentially malignant disorder associated with an increased risk of oral cancer. In Japan, the association of OLP with hepatitis C virus (HCV) infection is well documented. In the present study, a case of oral verrucous carcinoma arising from OLP coexisting vulvo-vaginal-gingival syndrome and esophageal squamous cell carcinoma (SCC) in a patient with HCV-related liver cirrhosis is reported. A 71-year old, non-smoking Japanese woman presented with lesions of OLP affecting the bilateral buccal mucosa, tongue, gingival, palate, oral floor and lower lip. Ten years later, an exophytic mass developed in the mandibular alveolar mucosa, the right buccal mucosa and the right lower lip. Pathological diagnosis confirmed the presence of verrucous carcinoma. However, she developed esophageal rather than oral cancer. The oral cancer was resected surgically three times and the patients underwent radiotherapy. The esophageal cancer was removed by endoscopic submucosal dissection. The risk of carcinogenesis increased as hyperinsulinemia continued. The results suggested that it is necessary to monitor for malignant changes in patients with OLP lesions and HCV infection. In addition, treatment requires the cooperation of various medical specialists, as well as an oral surgeon. PMID:24648893

  7. Potential to involve multiple effector cells with human recombinant interleukin-2 and antiganglioside monoclonal antibodies in a canine malignant melanoma immunotherapy model.

    PubMed

    Helfand, S C; Soergel, S A; Donner, R L; Gan, J; Hank, J A; Lindstrom, M J; Sondel, P M

    1994-10-01

    Human tumors originating from neuroectodermal cells such as malignant melanoma and neuroblastoma express high levels of disialogangliosides GD2 and GD3, making these antigens ideal for targeting by monoclonal antibodies (Mabs). The purpose of this study was to investigate expression and targeting of gangliosides on canine melanoma. Using immunohistochemical methods, we analyzed the expression of disialogangliosides GD2 and GD3 on canine oral malignant melanomas with murine Mabs 14.G2a and R24 that recognize GD2 and GD3 disialogangliosides, respectively, on human tumors. We also assessed the ability of Mab 14.G2a (and its mouse-human chimera, ch 14.18) to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro against a canine malignant melanoma cell line with human recombinant interleukin-2 (IL-2) activated canine peripheral blood lymphocytes (PBL), or canine neutrophil effector cells. Our data show that Mabs 14.G2a and R24 recognized fresh frozen canine oral melanoma. Mabs 14.G2a or ch 14.18, or IL-2, potentiated lysis of the canine malignant melanoma cell line by canine PBL. The killing effect observed using the combination of either Mab with IL-2 was additive. Mab 14.G2a mediated potent ADCC of canine melanoma by canine neutrophils. These studies indicate that disialogangliosides are expressed on fresh canine melanoma cells. Mabs reactive with these antigens can target and trigger tumor killing by multiple canine effector populations and IL-2 can potentiate these effects by canine lymphocytes. Thus, canine oral malignant melanoma, a spontaneously occurring, metastatic cancer in the dog, may be a relevant animal model to investigate combination immunotherapy using antitumor Mab and IL-2.

  8. Potential contribution of SIM2 and ETS2 functional polymorphisms in Down syndrome associated malignancies

    PubMed Central

    2013-01-01

    Background Proper expression and functioning of transcription factors (TFs) are essential for regulation of different traits and thus could be crucial for the development of complex diseases. Subjects with Down syndrome (DS) have a higher incidence of acute lymphoblastic leukemia (ALL) while solid tumors, like breast cancer (BC) and oral cancer (OC), show rare incidences. Triplication of the human chromosome 21 in DS is associated with altered genetic dosage of different TFs. V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) and Single Minded 2 (SIM2) are two such TFs that regulate several downstream genes involved in developmental and neurological pathways. Here we studied functional genetic polymorphisms (fSNP) in ETS2 and SIM2 encoding genes in a group of patients and control subjects to better understand association of these variants with DS phenotypes. Methods We employed an in silico approach to identify potential target pathways of ETS2 and SIM2. fSNPs in genes encoding for these two TFs were identified using available databases. Selected sites were genotyped in individuals with DS, their parents, ALL, BC, OC as well as ethnically matched control individuals. We further analyzed these data by population-based statistical methods. Results Allelic/genotypic association analysis showed significant (P < 0.03) differences of rs2070530, rs1051476, rs11254, rs711 for DS subjects compared to control. rs711 also exhibited significantly different genotypic distribution pattern in parents of DS probands (P < 0.02) and BC patients (P < 0.02). Interaction analysis revealed independent main effect of rs711 in all the groups, while rs11254 exhibited independent main effect in DS subjects only. High entropy values were noticed for rs461155 in the solid tumor groups. Significant interactive effects of rs2070531 with rs1051475, rs1051476, rs11254 were observed in all the groups except DS. Conclusions We infer from the present investigation that the

  9. Reactive hyperplasias,precancerous and malignant lesions of the oral mucosa.

    PubMed

    Krahl, Dieter; Altenburg, Andreas; Zouboulis, Christos C

    2008-03-01

    The oral cavity contains many organs and tissues compressed in a small area. Accordingly oral tumors have a wide variety of appearances. Reactive hyper-plastic lesions include epulis,morsicatio,traumatic ulcer or palatal hyperplasia. These benign lesions must be separated clinically and histologically from precancerous and neoplastic lesions. In leukoplakia,the individual risk can be estimated by clinical signs. Nevertheless histopathology is mandatory because precancerous lesions usually precede or accompany most oral cancers. Amalgam tattoo,oral nevi and melanoacanthoma have to be considered as differential diagnoses of oral melanoma. Accurate clinico-pathological diagnosis is mandatory to insure appropriate therapy. Oral soft tissue tumors such as Kaposi sarcoma and multiple mucosal neuromas in MEN 2b require interdisciplinary management. Diseases affecting the minor salivary glands which may be encountered by dermatologists include mucocele, necrotizing sialometa-plasia,and tumors such as pleomorphic adenoma.

  10. Transition of Immunohistochemical Expression of E-Cadherin and Vimentin from Premalignant to Malignant Lesions of Oral Cavity and Oropharynx

    PubMed Central

    Akhtar, Kafil; Ara, Anjum; Siddiqui, Shahid A; Sherwani, Rana K

    2016-01-01

    Objectives We sought to study the expression of epithelial-to-mesenchymal transition markers E-cadherin and vimentin in precancerous lesions of the oral cavity and oropharynx and to use the specific pattern of expression to predict invasiveness. Methods This cross-sectional study looked at 87 cases of oral and oropharyngeal lesions obtained between December 2012 and November 2014 in the Department of Pathology, Jawaharlal Nehru Medical College, Aligarh Muslim University, India. Fifty-three biopsies from the buccal mucosa, tongue, and pharynx and 34 resected oral specimens were evaluated for premalignant and malignant lesions using hematoxylin and eosin and immunohistochemical stains. Immunohistochemical expression of epithelial marker E-cadherin and mesenchymal marker vimentin was evaluated wherever possible. Slides were examined for staining pattern (cytoplasmic or membrane), proportion, and intensity of staining of tumor cells. Patients follow-up and therapy related changes were also studied. Results There were 64 premalignant and 23 malignant cases in our study with 65 (74.7%) cases seen in males and 22 (25.3%) cases seen in females. The majority of malignant cases, (n = 15; 64.2%) were seen in the fifth and sixth decades of life while most of the premalignant lesions (n = 36; 56.4%) were seen in the fourth and fifth decade. Amongst the 64 premalignant oral lesions, leukoplakia comprised of 14 cases (21.9%), of which three cases had associated mild to moderate dysplasia. The majority of premalignant lesions showed strong E-cadherin expression and decreased expression of vimentin with negative and weak expression in both dysplasias and carcinoma in situ (p = 0.013). E-cadherin expression was significantly reduced in invasive carcinomas compared to dysplasias and carcinoma in situ and the difference in immunoreactivity was statistically significant (p < 0.050). Vimentin expression increased as the tumor progressed from dysplasias to carcinoma in situ to invasive

  11. Adrenal oncoctyoma of uncertain malignant potential: a rare etiology of adrenal incidentaloma.

    PubMed

    Kedia, Rohit R; Muinov, Lucy; Lele, Subodh M; Shivaswamy, Vijay

    2016-03-01

    A rare cause for rapid adrenal enlargement is adrenal oncocytoma of uncertain malignant potential. A full biochemical evaluation is warranted to screen secreting adrenal adenomas as well as to evaluate adrenal cortical carcinoma. Careful pathologic evaluation is required as the diagnosis of AOC cannot be made by imaging. PMID:27014458

  12. Oral ciclopirox olamine displays biological activity in a phase I study in patients with advanced hematologic malignancies.

    PubMed

    Minden, Mark D; Hogge, Donna E; Weir, Scott J; Kasper, Jim; Webster, Debra A; Patton, Lavonne; Jitkova, Yulia; Hurren, Rose; Gronda, Marcela; Goard, Carolyn A; Rajewski, Lian G; Haslam, John L; Heppert, Kathleen E; Schorno, Kevin; Chang, Hong; Brandwein, Joseph M; Gupta, Vikas; Schuh, Andre C; Trudel, Suzanne; Yee, Karen W L; Reed, Gregory A; Schimmer, Aaron D

    2014-04-01

    The antimycotic ciclopirox olamine is an intracellular iron chelator that has anticancer activity in vitro and in vivo. We developed an oral formulation of ciclopirox olamine and conducted the first-in-human phase I study of this drug in patients with relapsed or refractory hematologic malignancies (Trial registration ID: NCT00990587). Patients were treated with 5-80 mg/m² oral ciclopirox olamine once daily for five days in 21-day treatment cycles. Pharmacokinetic and pharmacodynamic companion studies were performed in a subset of patients. Following definition of the half-life of ciclopirox olamine, an additional cohort was enrolled and treated with 80 mg/m² ciclopirox olamine four times daily. Adverse events and clinical response were monitored throughout the trial. Twenty-three patients received study treatment. Ciclopirox was rapidly absorbed and cleared with a short half-life. Plasma concentrations of an inactive ciclopirox glucuronide metabolite were greater than those of ciclopirox. Repression of survivin expression was observed in peripheral blood cells isolated from patients treated once daily with ciclopirox olamine at doses greater than 10 mg/m², demonstrating biological activity of the drug. Dose-limiting gastrointestinal toxicities were observed in patients receiving 80 mg/m² four times daily, and no dose limiting toxicity was observed at 40 mg/m² once daily. Hematologic improvement was observed in two patients. Once-daily dosing of oral ciclopirox olamine was well tolerated in patients with relapsed or refractory hematologic malignancies, and further optimization of dosing regimens is warranted in this patient population. PMID:24273151

  13. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast.

    PubMed

    Gatalica, Zoran; Vranic, Semir; Ghazalpour, Anatole; Xiu, Joanne; Ocal, Idris Tolgay; McGill, John; Bender, Ryan P; Discianno, Erin; Schlum, Aaron; Sanati, Souzan; Palazzo, Juan; Reddy, Sandeep; Pockaj, Barbara

    2016-01-12

    Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including VEGFA, Angiopoietin-2, VCAM1, PDGFRA, and PTTG1. EGFR protein overexpression was observed in 26/27 (96%) of cases with amplification of the EGFR gene in 8/24 (33%) cases. Two EGFR mutations were identified including EGFRvIII and a presumed pathogenic V774M mutation, respectively. The most common pathogenic mutations included TP53 (50%) and PIK3CA (15%). Cases with matched primary and metastatic tumors harbored identical mutations in both sites (PIK3CA/KRAS and RB1 gene mutations, respectively). Tumor expression of PD-L1 immunoregulatory protein was observed in 3/22 (14%) of cases. Overexpression of molecular biomarkers of increased angiogenesis, EGFR and immune checkpoints provides novel targeted therapy options in malignant phyllodes tumors of the breast.

  14. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast

    PubMed Central

    Gatalica, Zoran; Vranic, Semir; Ghazalpour, Anatole; Xiu, Joanne; Ocal, Idris Tolgay; McGill, John; Bender, Ryan P.; Discianno, Erin; Schlum, Aaron; Sanati, Souzan; Palazzo, Juan; Reddy, Sandeep; Pockaj, Barbara

    2016-01-01

    Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including VEGFA, Angiopoietin-2, VCAM1, PDGFRA, and PTTG1. EGFR protein overexpression was observed in 26/27 (96%) of cases with amplification of the EGFR gene in 8/24 (33%) cases. Two EGFR mutations were identified including EGFRvIII and a presumed pathogenic V774M mutation, respectively. The most common pathogenic mutations included TP53 (50%) and PIK3CA (15%). Cases with matched primary and metastatic tumors harbored identical mutations in both sites (PIK3CA/KRAS and RB1 gene mutations, respectively). Tumor expression of PD-L1 immunoregulatory protein was observed in 3/22 (14%) of cases. Overexpression of molecular biomarkers of increased angiogenesis, EGFR and immune checkpoints provides novel targeted therapy options in malignant phyllodes tumors of the breast. PMID:26625196

  15. Molecular Imaging of Oral Premalignant and Malignant Lesions Using Fluorescently Labeled Lectins

    PubMed Central

    Baeten, John; Suresh, Amritha; Johnson, Alexander; Patel, Ketan; Kuriakose, Moni; Flynn, Anita; Kademani, Deepak

    2014-01-01

    Aberrant glycosylation during carcinogenesis results in altered glycan expression on oral cancer cells. The objective of this study was to detect this atypical glycosylation via imaging of fluorophore-conjugated lectins. Paired normal and tumor tissue from seven patients with oral squamous cell carcinoma were investigated for sialic acid expression via the legume protein wheat germ agglutinin (WGA). Fluorophore (Alexa Fluor 350 and Alexa Fluor 647) conjugated WGA was topically applied to the tissue samples and imaged using a custom wide-field fluorescence imaging system. All seven patients had histologically confirmed disease with 6/7 exhibiting squamous cell carcinoma and 1/7 exhibiting dysplasia. Fluorescent data collected from all patients demonstrated that fluorophore conjugated WGA could distinguish between pathologically normal and diseased tissue with the average signal-to-noise ratio (SNR) among all patients being 5.88 (P = .00046). This SNR was statistically significantly higher than the SNR from differences in tissue autofluorescence (P = .0049). A lectin inhibitory experiment confirmed that lectin binding is molecularly specific to overexpressed tumor glycans and that fluorescence is not due to tissue optical properties or tissue diffusion differences. These results illustrate that changes in tumor glycan content of oral neoplasms can be detected with optical imaging using topically applied fluorescently labeled WGA. Lectin targeting of oral lesions using optical imaging may provide a new avenue for the early detection of oral cancers. PMID:24913673

  16. PAX2 Expression in Low Malignant Potential Ovarian Tumors and Low-Grade Ovarian Serous Carcinomas

    PubMed Central

    Tung, Celestine S.; Mok, Samuel C.; Tsang, Yvonne T.M.; Zu, Zhifei; Song, Huijuan; Liu, Jinsong; Deavers, Michael; Malpica, Anais; Wolf, Judith K.; Lu, Karen H.; Gershenson, David M.; Wong, Kwong-Kwok

    2009-01-01

    Ovarian tumors of low-malignant potential and low-grade ovarian serous carcinomas are thought to represent different stages on a tumorigenic continuum and to develop along pathways distinct from high-grade ovarian serous carcinoma. We performed gene expression profiling on 3 normal human ovarian surface epithelia samples, and 10 low-grade and 10 high-grade ovarian serous carcinomas. Analysis of gene expression profiles of these samples has identified 80 genes up-regulated and 232 genes down-regulated in low-grade ovarian serous carcinomas. PAX2 was found to be one of the most up-regulated genes in low-grade ovarian serous carcinoma. The up-regulation of PAX2 was validated by real-time quantitative RT-PCR, Western blot and immunohistochemical analyses. Real-time RT-PCR demonstrated a statistically significant difference in PAX2 mRNA expression (expressed as fold change in comparison to normal human ovarian surface epithelia) among ovarian tumors of low-malignant potential (1837.38, N=8), low-grade (183.12, N=17), and high-grade (3.72, N=23) carcinoma samples (p=0.015). Western blot analysis revealed strong PAX2 expression in ovarian tumors of low-malignant potential (67%, N=3) and low-grade carcinoma samples (50%, N=10) but no PAX2 protein expression in high-grade carcinomas (0%, N=10). Using immunohistochemistry, tumors of low-malignant potential (59%, N=17) and low-grade carcinoma (63%, N=16) samples expressed significantly stronger nuclear staining than high-grade ovarian carcinoma samples (9.1%, N=263). Furthermore, consistent with previous immunohistochemical findings, PAX2 expression was found to be expressed in the epithelial cells of fallopian tubes but not in normal ovarian surface epithelial cells. Our findings further support the two-tiered hypothesis that tumors of low-malignant potential and low-grade ovarian serous carcinoma are on a continuum and are distinct from high-grade ovarian carcinomas. Additionally, the absence of PAX2 expression in normal

  17. Exploring Therapeutic Potentials of Baicalin and Its Aglycone Baicalein for Hematological Malignancies

    PubMed Central

    Chen, Haijun; Gao, Yu; Wu, Jianlei; Chen, Yingyu; Chen, Buyuan; Hu, Jianda; Zhou, Jia

    2014-01-01

    Despite tremendous advances in the targeted therapy for various types of hematological malignancies with successful improvements in the survival rates, emerging resistance issues are startlingly high and novel therapeutic strategies are urgently needed. In addition, chemoprevention is currently becoming an elusive goal. Plant-derived natural products have garnered considerable attention in recent years due to the potential dual functions as chemotherapeutics and dietary chemoprevention. One of the particularly ubiquitous families is the polyphenolic flavonoids. Among them, baicalin and its aglycone baicalein have been widely investigated in hematological malignancies because both of them exhibit remarkable pharmacological properties. This review focuses on the recent achievements in drug discovery research associated with baicalin and baicalein for hematological malignancy therapies. The promising anticancer activities of these two flavonoids targeting diverse signaling pathways and their potential biological mechanisms in different types of hematological malignancies, as well as the combination strategy with baicalin or baicalein as chemotherapeutic adjuvants for recent therapies in these intractable diseases are discussed. Meanwhile, the biotransformation of baicalin and baicalein and the relevant approaches to improve their bioavailability are also summarized. PMID:25128647

  18. Therapeutic potential of melatonin in oral medicine and periodontology.

    PubMed

    Najeeb, Shariq; Khurshid, Zohaib; Zohaib, Sana; Zafar, Muhammad Sohail

    2016-08-01

    Melatonin (N-acetyl-5-methoxy tryptamine) is a substance secreted by multiple organs in vertebrates. In addition to playing a part in the circadian cycle of the body, melatonin is known to have antioxidant, antiinflammatory, and antioncotic effects on human tissues. Oral cavity is affected by a number of conditions such as periodontitis, mucositis, cancers, and cytotoxicity from various drugs or biomaterials. Research has suggested that melatonin is effective in treating the aforementioned pathologies. Furthermore, melatonin has been observed to enhance osseointegration and bone regeneration. The aim of this review is to critically analyze and summarize the research focusing on the potential of melatonin in the field of oral medicine. Topical administration of melatonin has a positive effect on periodontal health and osseointegration. Furthermore, melatonin is particularly effective in improving the periodontal parameters of diabetic patients with periodontitis. Melatonin exerts a regenerative effect on periodontal bone and may be incorporated into of periodontal scaffolds. The cytotoxic effect of various drugs and dental materials may be countered by the antioxidant properties of melatonin. Topical administration of melatonin promotes the healing of tooth extraction sockets and may also impede the progression of oral cancer. Although, there are a number of current and potential applications of melatonin, further long term clinical and animal studies are needed to assess its efficacy. Moreover, the role of melatonin supplements in the management of periodontitis should also be assessed. PMID:27523451

  19. Evaluating oral noncombustible potential-reduced exposure products for smokers

    PubMed Central

    Eissenberg, Thomas

    2010-01-01

    Introduction: Potential-reduced exposure products (PREPs) are marketed as a way for smokers to continue using tobacco while possibly lessening their tobacco toxicant intake. Some tobacco-based PREPs are combustible and intended to be smoked, while others are noncombustible and intended to be administered orally (e.g., Camel Snus [CS] tobacco sachets and Ariva tobacco tablets). The ability of these noncombustible PREPs to reduce smokers’ exposure to cigarette-delivered toxicants and suppress tobacco abstinence symptoms effectively is unclear. Clinical laboratory methods have been used to measure combustible PREP-associated toxicant exposure and abstinence symptom suppression and could be applied to evaluating the effects of orally administered noncombustible PREPs. Methods: In this study, 21 smokers (6 women) participated in four 5-day conditions that differed by product used: CS, Ariva, own brand cigarettes, or no tobacco. Measures included expired-air carbon monoxide (CO), the urinary metabolite of nicotine (cotinine), the urinary metabolite of the carcinogen NNK (NNAL-T), and subjective effect ratings. Results: Relative to own brand, all other conditions were associated with CO and cotinine levels that were lower and abstinence symptom ratings that were greater. Only no-tobacco use was associated with significantly lower NNAL levels. Acceptability ratings were also lower in all conditions relative to own brand. Discussion: Although these oral products reduce exposure to CO, their ineffective abstinence symptom suppression and low acceptability may limit their viability as PREPs. As with combustible PREPs, clinical laboratory study of orally administered noncombustible PREPs will be a valuable part of any comprehensive PREP evaluation strategy. PMID:20159791

  20. Current Understanding of Circulating Tumor Cells – Potential Value in Malignancies of the Central Nervous System

    PubMed Central

    Adamczyk, Lukasz A.; Williams, Hannah; Frankow, Aleksandra; Ellis, Hayley Patricia; Haynes, Harry R.; Perks, Claire; Holly, Jeff M. P.; Kurian, Kathreena M.

    2015-01-01

    Detection of circulating tumor cells (CTCs) in the blood via so-called “liquid biopsies” carries enormous clinical potential in malignancies of the central nervous system (CNS) because of the potential to follow disease evolution with a blood test, without the need for repeat neurosurgical procedures with their inherent risk of patient morbidity. To date, studies in non-CNS malignancies, particularly in breast cancer, show increasing reproducibility of detection methods for these rare tumor cells in the circulation. However, no method has yet received full recommendation to use in clinical practice, in part because of lack of a sufficient evidence base regarding clinical utility. In CNS malignancies, one of the main challenges is finding a suitable biomarker for identification of these cells, because automated systems, such as the widely used Cell Search system, are reliant on markers, such as the epithelial cell adhesion molecule, which are not present in CNS tumors. This review examines methods for CTC enrichment and detection, and reviews the progress in non-CNS tumors and the potential for using this technique in human brain tumors. PMID:26322014

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

    NASA Astrophysics Data System (ADS)

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

    2006-02-01

    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.

  2. LFA-1 expression on exocrine glands as a potential novel marker of malignant disease.

    PubMed

    Futagami-Mizoguchi, E; Yamada, A; Mizoguchi, A; Imai, Y; Yokoyama, M M

    1993-09-01

    The lymphocyte function associated antigen 1 has been found only on leukocytes and lymphoid tissues; however, the expression of lymphocyte function associated antigen 1 on nonhematopoietic cells has not been reported previously. In this study, immunohistochemical expression of lymphocyte function associated antigen 1 was examined on various tissues from 35 patients with malignant diseases and 36 patients with benign diseases including benign tumors. The expression of lymphocyte function associated antigen 1 was found on various exocrine tissues (eg, gastric glands, bronchial epithelium, alveolar epithelium, duodenal glands, bile ducts, pancreatic acini, and salivary glands) uninvolved by tumor in patients with malignant diseases. Localization of lymphocyte function associated antigen 1 was limited to the exocrine glands and differed from tissue-infiltrating leukocytes. The expression of lymphocyte function associated antigen 1 on exocrine tissues was confirmed in all 35 cases of malignant diseases that were examined. These included a wide spectrum of carcinomas and hematopoietic tumors. In contrast, none of the 36 cases with benign diseases examined expressed lymphocyte function associated antigen 1 on their exocrine glands. These results indicate a strong correlation between lymphocyte function associated antigen 1 expression on exocrine glands and malignant disease. The expression of lymphocyte function associated antigen 1 on nonhematopoietic cells was further confirmed in nonhematopoietic cell lines. Two of 19 nonhematopoietic cell lines (MKN45 and PANC-1; exocrine gland cell lines) examined expressed lymphocyte function associated antigen 1 on both cell surface and cytoplasm. These results suggested that immunohistochemically defined lymphocyte function associated antigen 1 molecules on nontumorous exocrine gland cells are a potential marker for the presence of malignant diseases.

  3. Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study

    PubMed Central

    Reardon, D A; Desjardins, A; Vredenburgh, J J; Gururangan, S; Sampson, J H; Sathornsumetee, S; McLendon, R E; Herndon, J E; Marcello, J E; Norfleet, J; Friedman, A H; Bigner, D D; Friedman, H S

    2009-01-01

    Background: We evaluated bevacizumab with metronomic etoposide among recurrent malignant glioma patients in a phase 2, open-label trial. Methods: A total of59 patients, including 27 with glioblastoma (GBM) and 32 with grade 3 malignant glioma, received 10 mg kg−1 bevacizumab biweekly and 50 mg m−2 etoposide daily for 21 consecutive days each month. The primary end point was a 6-month progression-free survival, and secondary end points included safety and overall survival. Vascular endothelial growth factor (VEGF), VEGFR-2, carbonic anhydrase 9 (CA9) and hypoxia-inducible factor-2α (HIF-2α) were assessed semiquantitatively in archival tumours using immunohistochemistry and were correlated with outcome. Results: Among grade 3 and GBM patients, the 6-month progression-free survivals were 40.6% and 44.4%, the radiographic response rates were 22% and 37% and the median survivals were 63.1 and 44.4 weeks, respectively. Hypertension predicted better outcome among both grade 3 and GBM patients, whereas high CA9 and low VEGF were associated with poorer progression-free survival (PFS) among those with GBM. The most common grade ⩾3 adverse events included neutropaenia (24%), thrombosis (12%), infection (8%) and hypertension (3%). Two patients had asymptomatic, grade 1 intracranial haemorrhage and one on-study death occurred because of pulmonary embolism. Conclusion: Bevacizumab with metronomic etoposide has increased toxicity compared with previous reports of bevacizumab monotherapy. Its anti-tumour activity is similar to that of bevacizumab monotherapy or bevacizumab plus irinotecan. (ClinicalTrials.gov: NCT00612430). PMID:19920819

  4. A Case of Oncocytic Adrenocortical Neoplasm of Borderline (Uncertain) Malignant Potential

    PubMed Central

    Brown, Linda G; Denning, Krista L; Pacioles, Toni

    2016-01-01

    Oncocytic neoplasms are tumors composed predominantly or exclusively of oncocytes (large polygonal cells with granular eosinophilic cytoplasm due to abnormal mitochondrial accumulation). These tumors are frequently reported in the thyroid, kidneys, and salivary glands. However, they are distinctly rare in the adrenal cortex. Oncocytic adrenocortical neoplasms (OAN) are classified regarding their biological behavior by their histological features according to the Lin-Weiss-Bisceglia system (LWB). Here, we report a case of OAN of borderline or uncertain malignant potential (BMP) with subsequently identified papillary thyroid carcinoma (PTC). A 34-year-old female with a nine-month history of fatigue presented with chest pain. A right adrenal mass was incidentally found while ruling out pulmonary embolism. A CT-guided adrenal biopsy, although not routinely indicated, was performed and interpreted as malignant with no definitive origin. Hormonal workup was unremarkable. PET-scan showed hypermetabolic adrenal mass with peak standardized uptake value of 15, suspicious of malignancy. A hypermetabolic thyroid nodule was also identified, but there was no evidence of metastatic disease. The patient underwent adrenalectomy, and the initial pathology report was interpreted as atypical pink cell tumor. A second pathology report from another laboratory favored OAN based on the morphology and immunohistochemical staining. While the histologic criteria of malignancy were not met, the large tumor size makes it compatible with BMP according to LWB criteria. A follow-up thyroid ultrasound revealed a complex thyroid nodule. A total thyroidectomy was performed, and pathology was consistent with PTC. Of interest, PTC frequently shows an increase in mitochondrial content, which is characteristic of oncocytic tumors. This case illustrates that OAN, although rare, should be considered in the differential diagnosis of adrenal masses. When OAN is identified, it should be classified

  5. A Case of Oncocytic Adrenocortical Neoplasm of Borderline (Uncertain) Malignant Potential.

    PubMed

    Shenouda, Mina; Brown, Linda G; Denning, Krista L; Pacioles, Toni

    2016-01-01

    Oncocytic neoplasms are tumors composed predominantly or exclusively of oncocytes (large polygonal cells with granular eosinophilic cytoplasm due to abnormal mitochondrial accumulation). These tumors are frequently reported in the thyroid, kidneys, and salivary glands. However, they are distinctly rare in the adrenal cortex. Oncocytic adrenocortical neoplasms (OAN) are classified regarding their biological behavior by their histological features according to the Lin-Weiss-Bisceglia system (LWB). Here, we report a case of OAN of borderline or uncertain malignant potential (BMP) with subsequently identified papillary thyroid carcinoma (PTC). A 34-year-old female with a nine-month history of fatigue presented with chest pain. A right adrenal mass was incidentally found while ruling out pulmonary embolism. A CT-guided adrenal biopsy, although not routinely indicated, was performed and interpreted as malignant with no definitive origin. Hormonal workup was unremarkable. PET-scan showed hypermetabolic adrenal mass with peak standardized uptake value of 15, suspicious of malignancy. A hypermetabolic thyroid nodule was also identified, but there was no evidence of metastatic disease. The patient underwent adrenalectomy, and the initial pathology report was interpreted as atypical pink cell tumor. A second pathology report from another laboratory favored OAN based on the morphology and immunohistochemical staining. While the histologic criteria of malignancy were not met, the large tumor size makes it compatible with BMP according to LWB criteria. A follow-up thyroid ultrasound revealed a complex thyroid nodule. A total thyroidectomy was performed, and pathology was consistent with PTC. Of interest, PTC frequently shows an increase in mitochondrial content, which is characteristic of oncocytic tumors. This case illustrates that OAN, although rare, should be considered in the differential diagnosis of adrenal masses. When OAN is identified, it should be classified

  6. A Case of Oncocytic Adrenocortical Neoplasm of Borderline (Uncertain) Malignant Potential.

    PubMed

    Shenouda, Mina; Brown, Linda G; Denning, Krista L; Pacioles, Toni

    2016-01-01

    Oncocytic neoplasms are tumors composed predominantly or exclusively of oncocytes (large polygonal cells with granular eosinophilic cytoplasm due to abnormal mitochondrial accumulation). These tumors are frequently reported in the thyroid, kidneys, and salivary glands. However, they are distinctly rare in the adrenal cortex. Oncocytic adrenocortical neoplasms (OAN) are classified regarding their biological behavior by their histological features according to the Lin-Weiss-Bisceglia system (LWB). Here, we report a case of OAN of borderline or uncertain malignant potential (BMP) with subsequently identified papillary thyroid carcinoma (PTC). A 34-year-old female with a nine-month history of fatigue presented with chest pain. A right adrenal mass was incidentally found while ruling out pulmonary embolism. A CT-guided adrenal biopsy, although not routinely indicated, was performed and interpreted as malignant with no definitive origin. Hormonal workup was unremarkable. PET-scan showed hypermetabolic adrenal mass with peak standardized uptake value of 15, suspicious of malignancy. A hypermetabolic thyroid nodule was also identified, but there was no evidence of metastatic disease. The patient underwent adrenalectomy, and the initial pathology report was interpreted as atypical pink cell tumor. A second pathology report from another laboratory favored OAN based on the morphology and immunohistochemical staining. While the histologic criteria of malignancy were not met, the large tumor size makes it compatible with BMP according to LWB criteria. A follow-up thyroid ultrasound revealed a complex thyroid nodule. A total thyroidectomy was performed, and pathology was consistent with PTC. Of interest, PTC frequently shows an increase in mitochondrial content, which is characteristic of oncocytic tumors. This case illustrates that OAN, although rare, should be considered in the differential diagnosis of adrenal masses. When OAN is identified, it should be classified

  7. Overexpression of BMP-2/4, -5 and BMPR-IA associated with malignancy of oral epithelium.

    PubMed

    Jin, Y; Tipoe, G L; Liong, E C; Lau, T Y; Fung, P C; Leung, K M

    2001-04-01

    The aim of the present study was to determine the relationships between bone morphogenetic proteins (BMPs), BMP receptor type IA and carcinogenesis of oral epithelium. A retrospective study was performed on material obtained from oral mucosa, including nine cases of normal mucosa (NB), eight cases of nonspecific chronic inflammation (NCI), seven cases of hyperkeratosis (HK), five cases of squamous cell papilloma (SCP), 29 cases of squamous cell carcinoma (SCC) with various grades of differentiation and 10 cases of epithelium adjacent to carcinoma (EAC). Six cases of NB from hard palate (NHP) were chosen as a control group. The benign groups consisted of NCI, HK and SCP. The antibodies against BMP-2/4, -5, receptor BMPR-IA and purified bovine BMP (bBMP-McAb) were utilised using an immunocytochemical method. The results demonstrated that the immunostaining of BMP-2/4, BMP-5, BMPR-IA and bBMP-McAb was weak and not consistent in normal and benign groups. The immunoreactivity level was independent of the clinical and pathological grading of SCC. All cases of SCC showed positive staining for BMP-2/4, BMP-5, BMPR-IA and bBMP-McAb except for three cases and one case of SCC which negatively stained for BMP-2/4 and BMP-5, respectively. The staining intensity and proportion of the positively stained cells were markedly increased in SCC when compared with that of the normal and benign groups except for EAC. The metastatic carcinoma cells in lymph nodes were strongly and positively stained for BMP-2/4 and BMP-5 when compared with the primary lesions. Our results indicate that there was an overexpression of BMP-2/4, BMP-5, bBMP-McAb and BMPR-IA in the high-risk premalignant and malignant lesions of oral epithelium. Our findings suggest that BMP-2/4 and BMP-5 but not BMPR-IA might be involved in the metastasis of oral carcinoma cells.

  8. Pediatric phase I trial of oral sorafenib and topotecan in refractory or recurrent pediatric solid malignancies.

    PubMed

    Reed, Damon R; Mascarenhas, Leo; Manning, Kathleen; Hale, Gregory A; Goldberg, John; Gill, Jonathan; Sandler, Eric; Isakoff, Michael S; Smith, Tiffany; Caracciolo, Jamie; Lush, Richard M; Juan, Tzu-Hua; Lee, Jae K; Neuger, Anthony M; Sullivan, Daniel M

    2016-02-01

    Targeted kinase inhibitors and camptothecins have shown preclinical and clinical activity in several cancers. This trial evaluated the maximum tolerated dose (MTD) and dose-limiting toxicities of sorafenib and topotecan administered orally in pediatric patients with relapsed solid tumors. Sorafenib was administered twice daily and topotecan once daily on days 1-5 and 8-12 of each 28-day course. The study utilized a standard 3 + 3 dose escalation design. Three dose levels (DL) were evaluated: (1) sorafenib 150 mg/m(2) and topotecan 1 mg/m(2) ; (2) sorafenib 150 mg/m(2) and topotecan 1.4 mg/m(2) ; and (3) sorafenib 200 mg/m(2) and topotecan 1.4 mg/m(2) . Pharmacokinetics were ascertained and treatment response assessed. Thirteen patients were enrolled. DL2 was the determined MTD. Grade 4 thrombocytopenia delaying therapy for >7 days was observed in one of six patients on DL2, and grade 4 neutropenia that delayed therapy in two of three patients on DL3. A patient with preexisting cardiac failure controlled with medication developed a transient drop in the left ventricular ejection fraction that improved when sorafenib was withheld. Sorafenib exposure with or without topotecan was comparable, and the concentration-time profiles for topotecan alone and in combination with sorafenib were similar. One objective response was noted in a patient with fibromatosis. We determined MTD to be sorafenib 150 mg/m(2) twice daily orally on days 1-28 combined with topotecan 1.4 mg/m(2) once daily on days 1-5 and 8-12. While these doses are 1 DL below the MTD of the agents individually, pharmacokinetic studies suggested adequate drug exposure without drug interactions. The combination had limited activity in the population studied.

  9. Ovarian tumors of low malignant potential (borderline tumors): immune morphology and current status.

    PubMed

    Neunteufel, W; Gitsch, G; Schieder, K; Kölbl, H; Breitenecker, G

    1989-01-01

    CA 125, CA 19-9 and CEA were demonstrated in tissue samples of 30 ovarian borderline tumors by immunohistochemistry. Of the 21 serous and 9 mucinous borderline tumors, 23 were in stage I and 7 stage III. None of the patients died of disease. All mucinous borderline tumors were CA 125 negative, 89% CA 19-9 positive and 44% CEA positive. 62% of the serous borderline tumors were CA 125 positive, 52% CA 19-9 and 19% CEA positive. Tumors of low malignant potential responded to CA 19-9 like invasive carcinomas. The incidence of positive responses to CA 125 ands CEA fell between that of benign and malignant tumors. The marker pattern did not correlate with tumor stage and cytological grading. The biological behavior of ovarian borderline tumors ranges between that of benign tumors and invasive carcinomas and cannot be classified as definitely belonging to either group. It is plausible that they are primarily of the borderline type, and not benign tumors that undergo malignant degeneration.

  10. Casein/pectin nanocomplexes as potential oral delivery vehicles.

    PubMed

    Luo, Yangchao; Pan, Kang; Zhong, Qixin

    2015-01-01

    Delivery systems prepared with natural biopolymers are of particular interests for applications in food, pharmaceutics and biomedicine. In this study, nanocomplex particles of sodium caseinate (NaCas) and pectin were fabricated and investigated as potential oral delivery vehicles. Nanocomplexes were prepared with three mass ratios of NaCas/pectin by acidification using glucono-δ-lactone and thermal treatment. NaCas/pectin at 1:1 mass ratio resulted in dispersions with the lowest turbidity and the smallest and most uniform nanocomplexes. Thermal treatment at 85 °C for 30 min facilitated the formation of stable, compact, and spherical nanocomplexes. Heating not only greatly increased the yield of nanocomplexes but also significantly improved the encapsulation capability of rutin studied as a model compound. Pectin in nanocomplexes delayed the hydrolysis of NaCas by pepsin at gastric conditions and enabled the controlled release of most rutin in simulated intestinal conditions. The nanocomplexes based on food-sourced biopolymers have promising features for oral delivery of nutrients and medicines.

  11. Essentials of oral cancer

    PubMed Central

    Rivera, César

    2015-01-01

    Oral cancer is one of the 10 most common cancers in the world, with a delayed clinical detection, poor prognosis, without specific biomarkers for the disease and expensive therapeutic alternatives. This review aims to present the fundamental aspects of this cancer, focused on squamous cell carcinoma of the oral cavity (OSCC), moving from its definition and epidemiological aspects, addressing the oral carcinogenesis, oral potentially malignant disorders, epithelial precursor lesions and experimental methods for its study, therapies and future challenges. Oral cancer is a preventable disease, risk factors and natural history is already being known, where biomedical sciences and dentistry in particular are likely to improve their poor clinical indicators. PMID:26617944

  12. Essentials of oral cancer.

    PubMed

    Rivera, César

    2015-01-01

    Oral cancer is one of the 10 most common cancers in the world, with a delayed clinical detection, poor prognosis, without specific biomarkers for the disease and expensive therapeutic alternatives. This review aims to present the fundamental aspects of this cancer, focused on squamous cell carcinoma of the oral cavity (OSCC), moving from its definition and epidemiological aspects, addressing the oral carcinogenesis, oral potentially malignant disorders, epithelial precursor lesions and experimental methods for its study, therapies and future challenges. Oral cancer is a preventable disease, risk factors and natural history is already being known, where biomedical sciences and dentistry in particular are likely to improve their poor clinical indicators. PMID:26617944

  13. The 1985 Walter Hubert lecture. Malignant cell differentiation as a potential therapeutic approach.

    PubMed Central

    Sartorelli, A. C.

    1985-01-01

    Most drugs available for cancer chemotherapy exert their effects through cytodestruction. Although significant advances have been attained with these cytotoxic agents in several malignant diseases, response is often accompanied by significant morbidity and many common malignant tumours respond poorly to existing cytotoxic therapy. Development of chemotherapeutic agents with non-cytodestructive actions appears desirable. Considerable evidence exists which indicates that (a) the malignant state is not irreversible and represents a disease of altered maturation, and (b) some experimental tumour systems can be induced by chemical agents to differentiate to mature end-stage cells with no proliferative potential. Thus, it is conceivable that therapeutic agents can be developed which convert cancer cells to benign forms. To study the phenomenon of blocked maturation, squamous carcinoma SqCC/Y1 cells were employed in culture. Using this system it was possible to demonstrate that physiological levels of retinoic acid and epidermal growth factor were capable of preventing the differentiation of these malignant keratinocytes into a mature tissue-like structure. The terminal differentiation caused by certain antineoplastic agents was investigated in HL-60 promyelocytic leukaemia cells to provide information on the mechanism by which chemotherapeutic agents induce cells to by-pass a maturation block. The anthracyclines aclacinomycin A and marcellomycin were potent inhibitors of N-glycosidically linked glycoprotein biosynthesis and transferrin receptor activity, and active inducers of maturation; temporal studies suggested that the biochemical effects were associated with the differentiation process. 6-Thioguanine produced cytotoxicity in parental cells by forming analog nucleotide. In hypoxanthine-guanine phosphoribosyltransferase negative HL-60 cells the 6-thiopurine initiated maturation; this action was due to the free base (and possibly the deoxyribonucleoside), a finding

  14. Serum and tissue PIVKA-II expression reflect the biological malignant potential of small hepatocellular carcinoma.

    PubMed

    Tamano, Masaya; Sugaya, Hitoshi; Oguma, Motoo; Iijima, Makoto; Yoneda, Masashi; Murohisa, Toshimitsu; Kojima, Kazuo; Kuniyoshi, Toru; Majima, Yuichi; Hashimoto, Takashi; Terano, Akira

    2002-04-01

    A sensitive method for measuring the serum level of protein-induced by vitamin K absence or antagonist II (PIVKA-II) has become so widely available that it is now used for the clinical diagnosis of small hepatocellular carcinoma (HCC). It is known that serum PIVKA-II can be a prognostic indicator for HCC, but there have been no detailed investigations concerning the tissue expression of PIVKA-II. The present study assessed the relationship between serum or tissue PIVKA-II and the biological malignant potential of HCC. The subjects were 25 patients with histologically confirmed HCC, that were solitary and 3 cm or less in diameter. Tissue PIVKA-II was detected by immunostaining using MU-3 as the primary antibody. The biological malignant potential of the tumors was evaluated on the basis of the Ki-67 labeling index of HCC cells and the tumor arterial vascularity assesed by angiography and CO(2) enhanced ultrasonography. The recurrence-free period after treatment was also evaluated. Among the 25 patients, eight were positive for tissue PIVKA-II. Serum PIVKA-II levels were significantly higher in the tissue PIVKA-II-positive patients compared with the negative patients, but serum and tissue PIVKA-II expressions were not consistently parallel. Tumor cell proliferation was closely correlated with the tissue PIVKA-II expression, while the recurrence-free period was correlated with the serum PIVKA-II level. Tumor arterial vascularity showed a strong correlation with the expression of both serum and tissue PIVKA-II. In conclusion, serum and tissue PIVKA-II expression reflect the biological malignant potential of HCC and thus may be useful indicators for the prognosis of small HCC.

  15. Potential of mid IR spectroscopy in the rapid label free identification of skin malignancies

    NASA Astrophysics Data System (ADS)

    Kastl, Lena; Kemper, Björn; Lloyd, Gavin R.; Nallala, Jayakrupakar; Stone, Nick; Naranjo, Valery; Penaranda, Francisco; Schnekenburger, Jürgen

    2016-03-01

    The rapid inspection of suspicious skin lesions for pathological cell types is the objective of optical point of care diagnostics technologies. A marker free fast diagnosis of skin malignancies would overcome the limitations of the current gold standard surgical biopsy. The time consuming and costly biopsy procedure requires the inspection of each sample by a trained pathologist, which limits the analysis of potentially malignant lesions. Optical technologies like RAMAN or infrared spectroscopy, which provide both, localization and chemical information, can be used to differentiate malignant from healthy tissue by the analysis of multi cell structures and cell type specific spectra. We here report the application of midIR spectroscopy towards fast and reliable skin diagnostics. Within the European research project MINERVA we developed standardized in vitro skin systems with increasing complexity, from single skin cell types as fibroblasts, keratinocytes and melanoma cells, to mixtures of these and finally three dimensional human skin equivalents. The standards were characterized in the established midIR range and also with newly developed systems for fast imaging up to 12 μm. The analysis of the spectra by novel data processing algorithms demonstrated the clear separation of all cell types, especially the tumor cells. The signals from single cell layers were sufficient for cell type differentiation. We have compared different midIR systems and found all of them suitable for specific cell type identification. Our data demonstrate the potential of midIR spectroscopy for fast image acquisition and an improved data processing as sensitive and specific optical biopsy technology.

  16. Round cell pattern of prostatic stromal tumor of uncertain malignant potential: a subtle newly recognized variant.

    PubMed

    Sadimin, Evita T; Epstein, Jonathan I

    2016-06-01

    Prostatic stromal tumor of uncertain malignant potential (STUMP) is a distinct entity which includes several different patterns. Four patterns of STUMP have been described including stroma with (1) degenerative atypia, (2) hypercellular spindle cells, (3) myxoid spindle cells, and (4) phyllodes-like pattern. The current study identified a novel round cell pattern. We searched our database from 1999 to 2015 and identified 7 patients with round cell pattern out of a total number of 98 patients with STUMP. All 7 cases showed mildly increased stromal cellularity with rounded nuclei, diagnosed on core biopsies in 5 cases, transurethral resection in 1 case, and radical prostatectomy in 1 case. Some degree of glandular displacement was observed in 4 cases. In 2 of the cases, STUMP was not recognized histologically by the referring pathologists and was initially diagnosed as benign prostatic hyperplasia. As has been described with other patterns of STUMP, several cases showed associated epithelial proliferations that in some instances masked the neoplastic stromal process. The round cell pattern of STUMP is a new deceptively subtle pattern that may not be recognized as a neoplasm and may be misdiagnosed as benign prostatic hyperplasia. Although there was no direct evidence in our study that the round cell pattern of STUMP has the same behavior as other variants of STUMPs, increased recognition of this entity will hopefully lead to additional studies to further understand its malignant potential. PMID:26980017

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

    PubMed

    Smolewski, P; Robak, T

    2011-11-01

    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

  18. In vitro evaluation of the suppressor potential of conditioned medium from benign myoepithelial cells from pleomorphic adenoma in malignant cell invasion.

    PubMed

    da Silva, Alessandra Dutra; Silva, Carolina Amália Barcellos; Montalli, Victor Angelo Martins; Martinez, Elizabeth Ferreira; de Araújo, Vera Cavalcanti; Furuse, Cristiane

    2012-09-01

    Tumoral invasion process is the result of a complex interaction between the tumor cells and microenvironment which plays an important role in modulating the growth and invasion of the cancer. The myoepithelial cells, present in glandular organs such as the breast and salivary glands, seem to exert paracrine effects on the glandular epithelium, acting as natural tumor suppressors. To verify the influence of the benign myoepithelial cells in the invasion of malignant cells, simulating an in situ carcinoma ex pleomorphic adenoma, we have cultured three different high-potential invasive malignant tumors (breast ductal adenocarcinoma, melanoma and oral squamous cell carcinoma) in conditioned medium of myoepithelial cells from salivary gland pleomorphic adenomas using transwell chambers with 8-μm pores membrane coated with matrigel. After 96 h, quantitative analyses of the results were performed by calculating the invasion index (number of cells that invaded in relation to the total number of cells). The results showed that there was a reduction of the invasion index mean for the three different malignant tumors. This study supports a tumoral suppressor function of the myoepithelial cells from pleomorphic adenoma in in vitro invasion process.

  19. Prostatic Stromal Tumor of Uncertain Malignant Potential Which Was Difficult to Diagnose

    PubMed Central

    Matsuyama, Satoko; Nohara, Takahiro; Kawaguchi, Shohei; Seto, Chikashi; Nakanishi, Yuko; Uchiyama, Akio; Ishizawa, Shin

    2015-01-01

    Here, we report a case of stromal tumor of uncertain malignant potential (STUMP) that was difficult to diagnose. A 53-year-old male was found to have a hard nodule on digital rectal examination; magnetic resonance imaging revealed a large nodule on the left side of the prostate, indicating prostate cancer. However, pathological diagnosis of the biopsy specimen was benign prostatic hyperplasia. Although a papillary tumor in the prostatic urethra was also seen on urethrocystoscopy, the tumor specimen obtained from transurethral resection was not malignant. The tumor in the prostatic urethra recurred only 3 months after transurethral resection, and pathological findings revealed benign hyperplasia not only in the stromal tissue but also in the epithelium; therefore, the prostate tumor was suspected to be STUMP. It took many prostate pathologists a long time to reach the final diagnosis of STUMP. STUMP is a rare benign tumor, difficult to diagnose, and sometimes transforms into stromal sarcoma. Thus, we should consider radical resection in such cases. PMID:26839730

  20. The EGF Receptor Promotes the Malignant Potential of Glioma by Regulating Amino Acid Transport System xc(-).

    PubMed

    Tsuchihashi, Kenji; Okazaki, Shogo; Ohmura, Mitsuyo; Ishikawa, Miyuki; Sampetrean, Oltea; Onishi, Nobuyuki; Wakimoto, Hiroaki; Yoshikawa, Momoko; Seishima, Ryo; Iwasaki, Yoshimi; Morikawa, Takayuki; Abe, Shinya; Takao, Ayumi; Shimizu, Misato; Masuko, Takashi; Nagane, Motoo; Furnari, Frank B; Akiyama, Tetsu; Suematsu, Makoto; Baba, Eishi; Akashi, Koichi; Saya, Hideyuki; Nagano, Osamu

    2016-05-15

    Extracellular free amino acids contribute to the interaction between a tumor and its microenvironment through effects on cellular metabolism and malignant behavior. System xc(-) is composed of xCT and CD98hc subunits and functions as a plasma membrane antiporter for the uptake of extracellular cystine in exchange for intracellular glutamate. Here, we show that the EGFR interacts with xCT and thereby promotes its cell surface expression and function in human glioma cells. EGFR-expressing glioma cells manifested both enhanced antioxidant capacity as a result of increased cystine uptake, as well as increased glutamate, which promotes matrix invasion. Imaging mass spectrometry also revealed that brain tumors formed in mice by human glioma cells stably overexpressing EGFR contained higher levels of reduced glutathione compared with those formed by parental cells. Targeted inhibition of xCT suppressed the EGFR-dependent enhancement of antioxidant capacity in glioma cells, as well as tumor growth and invasiveness. Our findings establish a new functional role for EGFR in promoting the malignant potential of glioma cells through interaction with xCT at the cell surface. Cancer Res; 76(10); 2954-63. ©2016 AACR.

  1. mTOR Inhibitors and Their Potential Role in Therapy in Leukemia and Other Haematologic Malignancies

    PubMed Central

    Teachey, David T.; Grupp, Stephan A.; Brown, Valerie I.

    2009-01-01

    Summary The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that functions as a key regulator of cell growth, protein synthesis, and cell-cycle progression through interactions with a number of signaling pathways, including PI3K/AKT, ras, TCL1, and BCR/ABL. Many haematologic malignancies have aberrant activation of the mTOR and related signaling pathways. Accordingly, mTOR inhibitors, a class of signal transduction inhibitors that were originally developed as immunosuppressive agents, are being investigated in preclinical models and clinical trials for a number of haematologic malignancies. Sirolimus and second generation mTOR inhibitors such as temsirolimus and everolimus, are safe and relatively well-tolerated, making them potentially attractive as single agents or in combination with conventional cytotoxics and other targeted therapies. Promising early clinical data suggests activity of mTOR inhibitors in a number of haematologic diseases, including acute lymphoblastic leukemia, chronic myelogenous leukemia, mantle cell lymphoma, anaplastic large cell lymphoma, and lymphoproliferative disorders. This review describes the rationale for using mTOR inhibitors in a variety of haematologic diseases with a focus on their use in leukemia. PMID:19344392

  2. Oral microbiota and cancer

    PubMed Central

    Meurman, Jukka H.

    2010-01-01

    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. PMID:21523227

  3. Microarray analysis of potential genes in the pathogenesis of recurrent oral ulcer

    PubMed Central

    Han, Jingying; He, Zhiwei; Li, Kun; Hou, Lu

    2015-01-01

    Recurrent oral ulcer seriously threatens patients’ daily life and health. This study investigated potential genes and pathways that participate in the pathogenesis of recurrent oral ulcer by high throughput bioinformatic analysis. RT-PCR and Western blot were applied to further verify screened interleukins effect. Recurrent oral ulcer related genes were collected from websites and papers, and further found out from Human Genome 280 6.0 microarray data. Each pathway of recurrent oral ulcer related genes were got through chip hybridization. RT-PCR was applied to test four recurrent oral ulcer related genes to verify the microarray data. Data transformation, scatter plot, clustering analysis, and expression pattern analysis were used to analyze recurrent oral ulcer related gene expression changes. Recurrent oral ulcer gene microarray was successfully established. Microarray showed that 551 genes involved in recurrent oral ulcer activity and 196 genes were recurrent oral ulcer related genes. Of them, 76 genes up-regulated, 62 genes down-regulated, and 58 genes up-/down-regulated. Total expression level up-regulated 752 times (60%) and down-regulated 485 times (40%). IL-2 plays an important role in the occurrence, development and recurrence of recurrent oral ulcer on the mRNA and protein levels. Gene microarray can be used to analyze potential genes and pathways in recurrent oral ulcer. IL-2 may be involved in the pathogenesis of recurrent oral ulcer. PMID:26722428

  4. Microarray analysis of potential genes in the pathogenesis of recurrent oral ulcer.

    PubMed

    Han, Jingying; He, Zhiwei; Li, Kun; Hou, Lu

    2015-01-01

    Recurrent oral ulcer seriously threatens patients' daily life and health. This study investigated potential genes and pathways that participate in the pathogenesis of recurrent oral ulcer by high throughput bioinformatic analysis. RT-PCR and Western blot were applied to further verify screened interleukins effect. Recurrent oral ulcer related genes were collected from websites and papers, and further found out from Human Genome 280 6.0 microarray data. Each pathway of recurrent oral ulcer related genes were got through chip hybridization. RT-PCR was applied to test four recurrent oral ulcer related genes to verify the microarray data. Data transformation, scatter plot, clustering analysis, and expression pattern analysis were used to analyze recurrent oral ulcer related gene expression changes. Recurrent oral ulcer gene microarray was successfully established. Microarray showed that 551 genes involved in recurrent oral ulcer activity and 196 genes were recurrent oral ulcer related genes. Of them, 76 genes up-regulated, 62 genes down-regulated, and 58 genes up-/down-regulated. Total expression level up-regulated 752 times (60%) and down-regulated 485 times (40%). IL-2 plays an important role in the occurrence, development and recurrence of recurrent oral ulcer on the mRNA and protein levels. Gene microarray can be used to analyze potential genes and pathways in recurrent oral ulcer. IL-2 may be involved in the pathogenesis of recurrent oral ulcer.

  5. Oral cancer

    MedlinePlus

    Cancer - mouth; Mouth cancer; Head and neck cancer; Squamous cell cancer - mouth; Malignant neoplasm - oral ... Oral cancer most commonly involves the lips or the tongue. It may also occur on the: Cheek lining Floor ...

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

    PubMed Central

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

    2009-01-01

    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. PMID:18211288

  7. Fenretinide Perturbs Focal Adhesion Kinase in Premalignant and Malignant Human Oral Keratinocytes. Fenretinide’s chemopreventive mechanisms include ECM interactions

    PubMed Central

    Han, Byungdo B.; Li, Suyang; Tong, Meng; Holpuch, Andrew S.; Spinney, Richard; Wang, Daren; Border, Michael B.; Liu, Zhongfa; Sarode, Sachin; Pei, Ping; Schwendeman, Steven; Mallery, Susan R.

    2015-01-01

    The membrane-associated protein, focal adhesion kinase (FAK), modulates cell-extracellular matrix interactions and also conveys pro-survival and proliferative signals. Notably, increased intraepithelial FAK levels accompany transformation of premalignant oral intraepithelial neoplasia (OIN) to oral squamous cell carcinoma (OSCC). OIN chemoprevention is a patient-centric, optimal strategy to prevent OSCC’s co-morbidities and mortality. The cancer chemopreventive and synthetic vitamin A derivative, fenretinide, has demonstrated protein-binding capacities e.g. mTOR and retinol binding protein interactions. These studies employed a continuum of human oral keratinocytes (normal-HPV E6/E7-transduced-OSCC) to assess potential fenretinide-FAK drug protein interactions and functional consequences on cellular growth regulation and motility. Molecular modeling studies demonstrated fenretinide has ~200-fold greater binding affinity relative to the natural ligand (ATP) at FAK’s kinase domain. Fenretinide also shows intermediate binding at FAK’s FERM domain and interacts at the ATP-binding site of the closest FAK analogue, Pyk2. Fenretinide significantly suppressed proliferation via induction of apoptosis and G2/M cell cycle blockade. Fenretinide-treated cells also demonstrated F-actin disruption, significant inhibition of both directed migration and invasion of a synthetic basement membrane, and decreased phosphorylation of growth-promoting kinases. A commercially available FAK inhibitor did not suppress cell invasion. Notably, while FAK’s FERM domain directs cell invasion, FAK inhibitors target the kinase domain. In addition, FAK-specific siRNA treated cells showed an intermediate cell migration capacity; data which suggest co-contribution of the established migrating-enhancing Pyk2. Our data imply that fenretinide is uniquely capable of disrupting FAK’s and Pyk2’s pro-survival and mobility-enhancing effects and further extend fenretinide’s chemopreventive

  8. CD8 T Cell–Independent Antitumor Response and Its Potential for Treatment of Malignant Gliomas

    PubMed Central

    Murphy, Katherine A.; Griffith, Thomas S.

    2016-01-01

    Malignant brain tumors continue to represent a devastating diagnosis with no real chance for cure. Despite an increasing list of potential salvage therapies, standard-of-care for these patients has not changed in over a decade. Immunotherapy has been seen as an exciting option, with the potential to offer specific and long lasting tumor clearance. The “gold standard” in immunotherapy has been the development of a tumor-specific CD8 T cell response to potentiate tumor clearance and immunological memory. While many advances have been made in the field of immunotherapy, few therapies have seen true success. Many of the same principles used to develop immunotherapy in tumors of the peripheral organs have been applied to brain tumor immunotherapy. The immune-specialized nature of the brain should call into question whether this approach is appropriate. Recent results from our own experiments require a rethinking of current dogma. Perhaps a CD8 T cell response is not sufficient for an organ as immunologically unique as the brain. Examination of previously elucidated principles of the brain’s immune-specialized status and known immunological preferences should generate discussion and experimentation to address the failure of current therapies. PMID:27472363

  9. CD8 T Cell-Independent Antitumor Response and Its Potential for Treatment of Malignant Gliomas.

    PubMed

    Murphy, Katherine A; Griffith, Thomas S

    2016-01-01

    Malignant brain tumors continue to represent a devastating diagnosis with no real chance for cure. Despite an increasing list of potential salvage therapies, standard-of-care for these patients has not changed in over a decade. Immunotherapy has been seen as an exciting option, with the potential to offer specific and long lasting tumor clearance. The "gold standard" in immunotherapy has been the development of a tumor-specific CD8 T cell response to potentiate tumor clearance and immunological memory. While many advances have been made in the field of immunotherapy, few therapies have seen true success. Many of the same principles used to develop immunotherapy in tumors of the peripheral organs have been applied to brain tumor immunotherapy. The immune-specialized nature of the brain should call into question whether this approach is appropriate. Recent results from our own experiments require a rethinking of current dogma. Perhaps a CD8 T cell response is not sufficient for an organ as immunologically unique as the brain. Examination of previously elucidated principles of the brain's immune-specialized status and known immunological preferences should generate discussion and experimentation to address the failure of current therapies. PMID:27472363

  10. Liquid biopsies for liquid tumors: emerging potential of circulating free nucleic acid evaluation for the management of hematologic malignancies

    PubMed Central

    Hocking, Jay; Mithraprabhu, Sridurga; Kalff, Anna; Spencer, Andrew

    2016-01-01

    Circulating free nucleic acids; cell free DNA and circulating micro-RNA, are found in the plasma of patients with hematologic and solid malignancies at levels higher than that of healthy individuals. In patients with hematologic malignancy cell free DNA reflects the underlying tumor mutational profile, whilst micro-RNAs reflect genetic interference mechanisms within a tumor and potentially the surrounding microenvironment and immune effector cells. These circulating nucleic acids offer a potentially simple, non-invasive, repeatable analysis that can aid in diagnosis, prognosis and therapeutic decisions in cancer treatment. PMID:27458529

  11. Potential role for inhibition of protein phosphatase 2A tumor suppressor in salivary gland malignancies.

    PubMed

    Routila, Johannes; Mäkelä, Juho-Antti; Luukkaa, Heikki; Leivo, Ilmo; Irjala, Heikki; Westermarck, Jukka; Mäkitie, Antti; Ventelä, Sami

    2016-01-01

    The aetiology and pathogenesis of salivary gland malignancies remain unknown. To reveal novel molecular factors behind the development of salivary gland cancer, we performed gene expression analyses from Smgb-Tag mouse salivary gland samples. The overall purpose was to apply these results for clinical use to find new approaches for both possible therapeutic targets and more accurate diagnostic tools. Smgb-Tag mouse strain, in which salivary neoplasms arise through a dysplastic phase in submandibular glands, was investigated using genome-wide microarray expression analysis, ingenuity pathway analysis, RT-PCR, and immunohistochemistry. Thirty-eight human salivary gland adenoid cystic carcinoma samples were investigated using immunohistochemistry for validation purposes. Our genome-wide study showed that Ppp2r1b, a PP2A subunit encoding tumor suppressor gene, is underexpressed in submandibular gland tumors of Smgb-Tag mice. mTOR signaling pathway was significantly enriched and mTOR linked PP2A subunit gene B55 gamma was significantly underexpressed in the analyses. Furthermore, parallel immunohistochemical analysis of three PP2A inhibitors demonstrated that two PP2A inhibitors, CIP2A and SET, are highly expressed in both dysplastic and adenocarcinomatous tumors of the Smgb-Tag mice. In addition, all 38 investigated human salivary adenoid cystic carcinoma samples stained positively for CIP2A and most for SET. Finally, p-S6 staining showed activation of mTOR pathway in human adenoid cystic carcinoma samples. Our results suggest that PP2A inhibition either via PP2A subunit underexpression or PP2A inhibitor overexpression play an important role in the formation of salivary gland malignancy, potentially due to mTOR signaling activation.

  12. Hypoxia-Related Marker GLUT-1, CAIX, Proliferative Index and Microvessel Density in Canine Oral Malignant Neoplasia

    PubMed Central

    Meier, Valeria; Guscetti, Franco; Roos, Malgorzata; Ohlerth, Stefanie; Pruschy, Martin; Rohrer Bley, Carla

    2016-01-01

    For various types of tumor therapy, it is suggested that co-targeting of tumor microenvironment, mainly tumor vasculature, mediates tumor response mechanisms. Immunohistochemistry for glucose transporter-1 (GLUT-1), carbonic anhydrase-IX (CAIX), Ki-67, and von Willebrand factor VIII for microvessel density (MVD) were performed on formalin-fixed paraffin-embedded samples of canine oral malignant neoplasms. Polarographic oxygen measurements (median pO2) and perfusion data via contrast-enhanced power Doppler ultrasound (median vascularity, median blood volume) provided additional information. Ninety-two samples were analyzed: sarcomas (n = 32), carcinomas (n = 30), and malignant melanomas (n = 30). Polarographic oxygen and perfusion data was available in 22.8% (sarcomas n = 9, carcinomas n = 7, melanomas n = 5), and 27.1% (sarcomas n = 10, carcinomas n = 8, melanomas n = 7) of cases, respectively. GLUT-1 expression was detected in 46.7% of all samples, and was generally weak. CAIX expression was found in 34.8% of all samples. Median Ki-67 score and MVD count was 19% and 17, respectively. The evaluation of the GLUT-1 score and continuous data showed significantly lower GLUT-1 levels in sarcomas (mean 5.1%, SD 6.2) versus carcinomas and melanomas (mean 16.5%/ 19.0%, SD 17.3/ 20.9, p = 0.001). The expression of CAIX correlated mildly positively with GLUT-1 (p = 0.018, rho = 0.250) as well as with Ki-67 (p = 0.014, rho = 0.295). MVD showed a significantly lower level in melanomas (mean 12.6, SD 7.7) versus sarcomas and carcinomas (mean 21.8/ 26.9, SD 13.0/20.4, p = 0.001). Median vascularity and blood volume were significantly lower in sarcomas (mean 10.4%, SD 11.0, and mean 6.3%, SD 6.5, respectively) versus carcinomas (mean 39.2%, SD 16.4 and mean 33.0%, SD 25.6, respectively) and melanomas (mean 36.0%, SD 18.3, and 31.5%, SD 24.5). Between the 3 histological groups, there was neither a significant difference in the GLUT-1 and CAIX score and continuous data, nor the Ki

  13. Malignant oral-maxillary neoplasm in children and adolescents. A retrospective analysis from the biopsy service at a school of dentistry in Argentina.

    PubMed

    Piloni, Maria Julia; Molina, Gladys; Keszler, Alicia

    2009-01-01

    There are few studies on oral-maxillary lesions in children and adolescents, and reports on malignant neoplasms are scarce. Comparison of available data is difficult due to the different criteria and racial-ethnic origin of the populations in each study. The aim of this work was to perform a retrospective study of malignant oral neoplasms in patients aged up to 20 years diagnosed at a center specialized in histopathological diagnosis of oral diseases between 1990 and 2005. The 24 retrieved cases accounted for 0.9% (n: 2434) of total biopsies in this age group during that period, and for 8.4% (n: 236) of the tumors. Mean age of the whole population was 9.2 years with even distribution according to sex. The most frequent tumor types were extranodal non-Hodgkin lymphoma (7 cases), osteosarcoma (4 cases) and Ewing sarcoma (3 cases). These data can be considered representative of our population of children and adolescents and serve as a basis for recognition and presumptive diagnosis in clinical practice. PMID:20302224

  14. Salivary detection of human Papilloma virus 16 & 18 in pre-malignant and malignant lesions of oral cavity: Is it feasible in Pakistani context of Socio-Cultural Taboos?

    PubMed Central

    Khyani, Iqbal A. Muhammad; Qureshi, Masood A.; Mirza, Talat; Farooq, M. Umar

    2015-01-01

    Objective: To evaluate salivary detection of HPV-16 & 18 would be feasible and informative biomarker for oral pre-malignant and malignant lesion in our population. Methods: This non-interventional, case control study was carried out at department of E.N.T, Head and Neck Surgery, Dow University of Health Sciences, Dow Medical College and Civil Hospital Karachi, Pakistan between July 2011 to December 2012. Total of 105 cases were recruited. These were divided in three groups ‘A’, ‘B’ & ‘C’ having 35 subjects each. Group‘A’ constitutes patients having strong clinical evidence of oral pre-malignant lesions (PML). Group ‘B’ includes histologically proven oral squamous cell carcinoma (OSCC) and Group ‘C’ comprised disease free subjects as controls. After taking informed consent, relevant clinical history was recorded on institutional approved performa. Saliva from all subjects was procured by standard ‘drooling method’. Samples were stored at +4°C and later transferred to Laboratory to store at-20°C before further process. Samples were centrifuged at 4500 rpm for 15 minutes at 4°C. Cell pellets sediments were used for identification of HPV-16 & 18 by real-time PCR method. Data was entered and analysed using SPSS version 16. P-value of 0.05 was taken as standard. Results: In group ‘A’, HPV-16 was detected in 3 (8.6%) cases while HPV-18 was not detected in any of the subject. In group ‘B’, HPV-16 was detected in 07 (20%) while HPV-18 was found in 06 (17.1%) cases. Mixed HPV-16 and HPV-18 were found in 02 (5.7%) cases. In group ‘C’, HPV-16 was detected in 03(8.6%) while HPV-18 was not detected in any of the subjects. Significant relationship was observed between the groups for HPV-18 detection (P= 0.002) while for HPV-16, no significant association was found (P= 0.245). Conclusion: HPV infection for the causation of oral cancer cannot be fully established possibly due to small sample size. More over differences in genetic makeup

  15. Chromatin Phenotype Karyometry Can Predict Recurrence in Papillary Urothelial Neoplasms of Low Malignant Potential

    PubMed Central

    Montironi, Rodolfo; Scarpelli, Marina; Lopez-Beltran, Antonio; Mazzucchelli, Roberta; Alberts, David; Ranger-Moore, James; Bartels, Hubert G.; Hamilton, Peter W.; Einspahr, Janine; Bartels, Peter H.

    2007-01-01

    Background: A preceding exploratory study (J. Clin. Pathol. 57(2004), 1201–1207) had shown that a karyometric assessment of nuclei from papillary urothelial neoplasms of low malignant potential (PUNLMP) revealed subtle differences in phenotype which correlated with recurrence of disease. Aim of the Study: To validate the results from the exploratory study on a larger sample size. Materials: 93 karyometric features were analyzed on haematoxylin and eosin-stained sections from 85 cases of PUNLMP. 45 cases were from patients who had a solitary PUNLMP lesion and were disease-free during a follow-up period of at least 8 years. The other 40 were from patients with a unifocal PUNLMP, with one or more recurrences in the follow-up. A combination of the previously defined classification functions together with a new P-index derived classification method was used in an attempt to classify cases and identify a biomarker of recurrence in PUNLMP lesions. Results: Validation was pursued by a number of separate approaches. First, the exact procedure from the exploratory study was applied to the large validation set. Second, since the discriminant function 2 of the exploratory study had been based on a small sample size, a new discriminant function was derived. The case classification showed a correct classification of 61% for non-recurrent and 74% for recurrent cases, respectively. Greater success was obtained by applying unsupervised learning technologies to take advantage of phenotypical composition (correct classification of 92%). This approach was validated by dividing the data into training and test sets with 2/3 of the cases assigned to the training sets, and 1/3 to the test sets, on a rotating basis, and validation of the classification rate was thus tested on three separate data sets by a leave-k-out process. The average correct classification was 92.8% (training set) and 84.6% (test set). Conclusions: Our validation study detected subvisual differences in chromatin

  16. The Continuum of Serous Tumors of Low Malignant Potential and Low-Grade Serous Carcinomas of the Ovary

    PubMed Central

    Wong, Kwong-Kwok; Gershenson, David

    2007-01-01

    The role of serous tumors of low malignant potential (LMP) in the development of invasive epithelial cancer of the ovary is debatable. This review summarizes the current clinical, genetic, and genomic evidence for the existence of a continuum comprising both LMP serous tumors and low-grade serous ovarian carcinomas. PMID:18057521

  17. Fenofibrate Suppresses Oral Tumorigenesis via Reprogramming Metabolic Processes: Potential Drug Repurposing for Oral Cancer.

    PubMed

    Jan, Chia-Ing; Tsai, Ming-Hsui; Chiu, Chang-Fang; Huang, Yi-Ping; Liu, Chia Jen; Chang, Nai Wen

    2016-01-01

    One anticancer strategy suggests targeting mitochondrial metabolism to trigger cell death through slowing down energy production from the Warburg effect. Fenofibrate is a clinical lipid-lowering agent and an effective anticancer drug. In the present study, we demonstrate that fenofibrate provided novel mechanisms for delaying oral tumor development via the reprogramming of metabolic processes. Fenofibrate induced cytotoxicity by decreasing oxygen consumption rate (OCR) that was accompanied with increasing extracellular acidification rate (ECAR) and reducing ATP content. Moreover, fenofibrate caused changes in the protein expressions of hexokinase II (HK II), pyruvate kinase, pyruvate dehydrogenase, and voltage-dependent anion channel (VDAC), which are associated with the Warburg effect. In addition, fenofibrate reprogrammed the metabolic pathway by interrupting the binding of HK II to VDAC. In an oral cancer mouse model, fenofibrate exhibited both preventive and therapeutic efficacy on oral tumorigenesis. Fenofibrate administration suppressed the incidence rate of tongue lesions, reduced the tumor sizes, decreased the tumor multiplicity, and decreased the immunoreactivities of VDAC and mTOR. The molecular mechanisms involved in fenofibrate's ability to delay tumor development included the down-regulation of mTOR activity via TSC1/2-dependent signaling through activation of AMPK and inactivation of Akt, or via a TSC1/2-independent pathway through direct suppression of raptor. Our findings provide a molecular rationale whereby fenofibrate exerts anticancer and additional beneficial effects for the treatment of oral cancer patients. PMID:27313493

  18. Fenofibrate Suppresses Oral Tumorigenesis via Reprogramming Metabolic Processes: Potential Drug Repurposing for Oral Cancer

    PubMed Central

    Jan, Chia-Ing; Tsai, Ming-Hsui; Chiu, Chang-Fang; Huang, Yi-Ping; Liu, Chia Jen; Chang, Nai Wen

    2016-01-01

    One anticancer strategy suggests targeting mitochondrial metabolism to trigger cell death through slowing down energy production from the Warburg effect. Fenofibrate is a clinical lipid-lowering agent and an effective anticancer drug. In the present study, we demonstrate that fenofibrate provided novel mechanisms for delaying oral tumor development via the reprogramming of metabolic processes. Fenofibrate induced cytotoxicity by decreasing oxygen consumption rate (OCR) that was accompanied with increasing extracellular acidification rate (ECAR) and reducing ATP content. Moreover, fenofibrate caused changes in the protein expressions of hexokinase II (HK II), pyruvate kinase, pyruvate dehydrogenase, and voltage-dependent anion channel (VDAC), which are associated with the Warburg effect. In addition, fenofibrate reprogrammed the metabolic pathway by interrupting the binding of HK II to VDAC. In an oral cancer mouse model, fenofibrate exhibited both preventive and therapeutic efficacy on oral tumorigenesis. Fenofibrate administration suppressed the incidence rate of tongue lesions, reduced the tumor sizes, decreased the tumor multiplicity, and decreased the immunoreactivities of VDAC and mTOR. The molecular mechanisms involved in fenofibrate's ability to delay tumor development included the down-regulation of mTOR activity via TSC1/2-dependent signaling through activation of AMPK and inactivation of Akt, or via a TSC1/2-independent pathway through direct suppression of raptor. Our findings provide a molecular rationale whereby fenofibrate exerts anticancer and additional beneficial effects for the treatment of oral cancer patients. PMID:27313493

  19. First International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions).

    PubMed

    Rageth, Christoph J; O'Flynn, Elizabeth Am; Comstock, Christopher; Kurtz, Claudia; Kubik, Rahel; Madjar, Helmut; Lepori, Domenico; Kampmann, Gert; Mundinger, Alexander; Baege, Astrid; Decker, Thomas; Hosch, Stefanie; Tausch, Christoph; Delaloye, Jean-François; Morris, Elisabeth; Varga, Zsuzsanna

    2016-09-01

    The purpose of this study is to obtain a consensus for the therapy of B3 lesions. The first International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions) including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), papillary lesions (PL), benign phyllodes tumors (PT), and radial scars (RS) took place in January 2016 in Zurich, Switzerland organized by the International Breast Ultrasound School and the Swiss Minimally Invasive Breast Biopsy group-a subgroup of the Swiss Society of Senology. Consensus recommendations for the management and follow-up surveillance of these B3 lesions were developed and areas of research priorities were identified. The consensus recommendation for FEA, LN, PL, and RS diagnosed on core needle biopsy or vacuum-assisted biopsy (VAB) is to therapeutically excise the lesion seen on imaging by VAB and no longer by open surgery, with follow-up surveillance imaging for 5 years. The consensus recommendation for ADH and PT is, with some exceptions, therapeutic first-line open surgical excision. Minimally invasive management of selected B3 lesions with therapeutic VAB is acceptable as an alternative to first-line surgical excision. PMID:27522516

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

    PubMed

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

    2013-05-01

    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.

  1. Kinesin family members KIF11 and KIF23 as potential therapeutic targets in malignant pleural mesothelioma.

    PubMed

    Kato, Tatsuya; Lee, Daiyoon; Wu, Licun; Patel, Priya; Young, Ahn Jin; Wada, Hironobu; Hu, Hsin-Pei; Ujiie, Hideki; Kaji, Mitsuhito; Kano, Satoshi; Matsuge, Shinichi; Domen, Hiromitsu; Kaga, Kichizo; Matsui, Yoshiro; Kanno, Hiromi; Hatanaka, Yutaka; Hatanaka, Kanako C; Matsuno, Yoshihiro; de Perrot, Marc; Yasufuku, Kazuhiro

    2016-08-01

    Malignant pleural mesothelioma (MPM) is a rare and aggressive form of cancer commonly associated with asbestos exposure that stems from the thoracic mesothelium with high mortality rate. Currently, treatment options for MPM are limited, and new molecular targets for treatments are urgently needed. Using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and an RNA interference-based screening, we screened two kinesin family members as potential therapeutic targets for MPM. Following in vitro investigation of the target silencing effects on MPM cells, a total of 53 MPMs were analyzed immunohistochemically with tissue microarray. KIF11 and KIF23 transcripts were found to be overexpressed in the majority of clinical MPM samples as well as human MPM cell lines as determined by quantitative RT-PCR. Gene knockdown in MPM cell lines identified growth inhibition following knockdown of KIF11 and KIF23. High expression of KIF11 (KIF11-H) and KIF23 (KIF23-H) were found in 43.4 and 50.9% of all the MPM cases, respectively. Patients who received curative resection with tumors displaying KIF23-H showed shorter overall survival (P=0.0194). These results provide that inhibition of KIF11 and KIF23 may hold promise for treatment of MPMs, raising the possibility that kinesin-based drug targets may be developed in the future. PMID:27279560

  2. Potential therapeutic effects of oral bisphosphonates on the intestine.

    PubMed

    Pazianas, Michael; Russell, R Graham G

    2011-12-01

    Bisphosphonates are the principal drugs prescribed for the prevention of osteoporotic fractures. They are bone specific but poorly absorbed. In oral formulations, almost 99% of the administered dose remains within the intestinal tract and reaches the small and large bowel. Although the nitrogen-containing bisphosphonates can irritate the distal esophageal/gastric mucosa, they improve drug-induced colitis in animal models and exhibit antitumor properties on intestinal cells in vitro. Several recent epidemiological studies provide evidence of a reduced risk of colorectal cancer in osteoporotic patients treated with oral bisphosphonates, notably alendronate. In this review, we will explore the possible mechanisms of action underlying these effects and raise the question of whether these agents might be used in the chemoprophylaxis against colorectal cancer.

  3. Potential Benefits of Oral Cryotherapy for Chemotherapy-Induced Mucositis.

    PubMed

    Wodzinski, Amelia

    2016-10-01

    Mucositis is a common side effect of cancer therapies that causes painful, erythematous lesions to develop in the gastrointestinal tract. These lesions can lead to malnutrition, increased risk for serious infection, prolonged hospital stays, and reduced quality of life. Oral cryotherapy, or the use of ice chips to cool the mucous membranes during bolus chemotherapy infusions (e.g., 5-fluorouracil [Adrucil®] and melphalan [Alkeran®]), is the most readily accessible and cost-effective intervention available. Although many factors may contribute to the development of mucositis during cancer treatment, studies have found a reduction in the incidence and the severity of mucositis with the use of oral cryotherapy.
. PMID:27668364

  4. Morphology as a risk factor for the malignant potential of T2 colorectal cancer

    PubMed Central

    Mori, Yuichi; Kudo, Shin-Ei; Endo, Shungo; Maeda, Chiyo; Mukai, Shumpei; Maeda, Yasuharu; Kataoka, Shinichi; Takeda, Kenichi; Ichimasa, Katsuro; Miyachi, Hideyuki; Sawada, Naruhiko; Hidaka, Eiji; Ishida, Fumio

    2016-01-01

    Currently, depressed type T1 colorectal cancer is often detected and its malignant potential is being revealed. However, few reports have focused on the morphology of T2 colorectal cancer types. The aim of the present retrospective study was to clarify the characteristics of colorectal T2 cancer types derived from depressed type T1 cancer. The present study included 195 patients with colorectal T2 cancer surgically resected at a referral hospital between April 2001 and April 2009. A total of 48 lesions (25%) with lymph node metastasis and 4 (2%) with distant metastasis were found. The lesions were classified by their form during endoscopy into four categories: Group A, depressed type (the periphery consists of normal mucosa); group B, laterally spreading type; group C, protruded type; group D, ulcerative type (the periphery consists of neoplastic mucosa). Tumor size, lymphatic and venous involvement, lymph node metastasis, and distant metastasis were compared between the four categories. The distribution of patients were as follows: Group A, 73 (37%), group B, 26 (13%), group C, 24 (12%) and group D, 72 (37%). The average tumor size for each category was 23, 51, 30 and 36 mm for groups A, B, C and D, respectively. The number of positive findings for lymphatic involvement, venous involvement, lymph node metastasis and distant metastasis for each category were: Group A, 50 (69%), 54 (74%), 19 (26%) and 1 (1%); group B, 14 (54%), 12 (46%), 8 (31%) and 0 (0%); group C, 14 (58%), 8 (33%), 6 (25%) and 0 (0%); group D 35 (49%), 41 (57%), 16 (22%) and 3 (4%). Group A demonstrated a significantly smaller tumor size (P<0.01), and higher rates of lymphatic and venous involvement (P=0.0333 and P=0.0019, respectively). No significant differences were observed between categories with regards to nodal and distant metastases. Of the T2 cancer types, ~40% were the depressed type. Compared with the other forms, depressed type lesions exhibited a smaller tumor size, and higher rates

  5. Extraction of RNA from archival tissues and measurement of thrombospondin-1 mRNA in normal, dysplastic, and malignant oral tissues.

    PubMed

    Macluskey, M; Baillie, R; Morrow, H; Schor, S L; Schor, A M

    2006-04-01

    Thrombospondin-1 (TSP-1) is an extracellular matrix glycoprotein implicated in the regulation of angiogenesis and tumour development. Our objectives were to ascertain the quantity and quality of RNA extracted from archival, formalin-fixed, paraffin embedded, oral tissues and their application in measuring the concentrations of TSP-1 mRNA in these tissues. We compared three techniques of isolation of RNA as well as related experimental variables. TSP-1 mRNA was measured in specimens of normal, dysplastic, and malignant oral tissues by real-time reverse transcriptase polymerase chain reaction (RT-PCR). RNA suitable for analysis by real-time RT-PCR was obtained by the three techniques tested, although the yield varied depending on the protocol used (range 0.2-3.6 microg/mm(3)). The mean (S.D.) concentrations of TSP-1 mRNA relative to 18S were 21.1 (7.2) in normal oral tissues (n=9), 11.0 (8.2) in dysplastic tissue (n=8) and 7.3 (5.3) in carcinomatous tissue (n=17). The difference between normal and carcinomatous specimens was significant (p=0.01). This reduction in expression of TSP-1 mRNA from normal to dysplasia to carcinoma may favour the angiogenic drive that accompanies the development of oral tumours.

  6. Potential Application of Temozolomide in Mesenchymal Stem Cell-Based TRAIL Gene Therapy Against Malignant Glioma

    PubMed Central

    Kim, Seong Muk; Woo, Ji Sun; Jeong, Chang Hyun; Ryu, Chung Heon; Jang, Jae-Deog

    2014-01-01

    Because the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells, it is one of the most promising candidates for cancer treatment. TRAIL-secreting human mesenchymal stem cells (MSC-TRAIL) provide targeted and prolonged delivery of TRAIL in glioma therapy. However, acquired resistance to TRAIL of glioma cells is a major problem to be overcome. We showed a potential therapy that used MSC-TRAIL combined with the chemotherapeutic agent temozolomide (TMZ). The antitumor effects of the combination with MSC-TRAIL and TMZ on human glioma cells were determined by using an in vitro coculture system and an in vivo experimental xenografted mouse model. Intracellular signaling events that are responsible for the TMZ-mediated sensitization to TRAIL-induced apoptosis were also evaluated. Treatment of either TRAIL-sensitive or -resistant human glioma cells with TMZ and MSC-TRAIL resulted in a significant enhancement of apoptosis compared with the administration of each agent alone. We demonstrated that TMZ effectively increased the sensitivity to TRAIL-induced apoptosis via extracellular signal-regulated kinase-mediated upregulation of the death receptor 5 and downregulation of antiapoptotic proteins, such as X-linked inhibitor of apoptosis protein and cellular FLICE-inhibitory protein. Subsequently, this combined treatment resulted in a substantial increase in caspase activation. Furthermore, in vivo survival experiments and bioluminescence imaging analyses showed that treatment using MSC-TRAIL combined with TMZ had greater therapeutic efficacy than did single-agent treatments. These results suggest that the combination of clinically relevant TMZ and MSC-TRAIL is a potential therapeutic strategy for improving the treatment of malignant gliomas. PMID:24436439

  7. Potential strategies to ameliorate risk of radiotherapy-induced second malignant neoplasms.

    PubMed

    Martin, Olga A; Yin, Xiaoyu; Forrester, Helen B; Sprung, Carl N; Martin, Roger F

    2016-06-01

    This review is aimed at the issue of radiation-induced second malignant neoplasms (SMN), which has become an important problem with the increasing success of modern cancer radiotherapy (RT). It is imperative to avoid compromising the therapeutic ratio while addressing the challenge of SMN. The dilemma is illustrated by the role of reactive oxygen species in both the mechanisms of tumor cell kill and of radiation-induced carcinogenesis. We explore the literature focusing on three potential routes of amelioration to address this challenge. An obvious approach to avoiding compromise of the tumor response is the use of radioprotectors or mitigators that are selective for normal tissues. We also explore the opportunities to avoid protection of the tumor by topical/regional radioprotection of normal tissues, although this strategy limits the scope of protection. Finally, we explore the role of the bystander/abscopal phenomenon in radiation carcinogenesis, in association with the inflammatory response. Targeted and non-targeted effects of radiation are both linked to SMN through induction of DNA damage, genome instability and mutagenesis, but differences in the mechanisms and kinetics between targeted and non-targeted effects may provide opportunities to lessen SMN. The agents that could be employed to pursue each of these strategies are briefly reviewed. In many cases, the same agent has potential utility for more than one strategy. Although the parallel problem of chemotherapy-induced SMN shares common features, this review focuses on RT associated SMN. Also, we avoid the burgeoning literature on the endeavor to suppress cancer incidence by use of antioxidants and vitamins either as dietary strategies or supplementation. PMID:26721424

  8. Paclitaxel-loaded ethosomes®: potential treatment of squamous cell carcinoma, a malignant transformation of actinic keratoses.

    PubMed

    Paolino, Donatella; Celia, Christian; Trapasso, Elena; Cilurzo, Felisa; Fresta, Massimo

    2012-05-01

    Topical application of anticancer drugs for the treatment of malignancies represents a new challenge in dermatology, potentially being an alternative therapeutic approach for the efficacious treatment of non-melanoma skin cancer, that is, actinic keratoses, and malignant lesions of the skin caused by ultraviolet radiation. Anti-proliferative and antimitotic drugs, including many of the taxanes, are currently under investigation for the treatment of cutaneous malignant transformation of actinic keratoses, particularly the squamous cell carcinoma. Paclitaxel-loaded ethosomes® are proposed as topical drug delivery systems for the treatment of this pathology due to their suitable physicochemical characteristics and enhanced skin penetration ability for deep dermal delivery. Our in vitro data show that the skin application of paclitaxel-loaded ethosomes® improved the permeation of paclitaxel in a stratum corneum-epidermis membrane model and increased its anti-proliferative activity in a squamous cell carcinoma model as compared to the free drug. The results obtained encouraged the use of the paclitaxel-loaded ethosomes® as the formulation for the potential treatment of squamous cell carcinoma, a malignant transformation of actinic keratoses.

  9. Paclitaxel-loaded ethosomes®: potential treatment of squamous cell carcinoma, a malignant transformation of actinic keratoses.

    PubMed

    Paolino, Donatella; Celia, Christian; Trapasso, Elena; Cilurzo, Felisa; Fresta, Massimo

    2012-05-01

    Topical application of anticancer drugs for the treatment of malignancies represents a new challenge in dermatology, potentially being an alternative therapeutic approach for the efficacious treatment of non-melanoma skin cancer, that is, actinic keratoses, and malignant lesions of the skin caused by ultraviolet radiation. Anti-proliferative and antimitotic drugs, including many of the taxanes, are currently under investigation for the treatment of cutaneous malignant transformation of actinic keratoses, particularly the squamous cell carcinoma. Paclitaxel-loaded ethosomes® are proposed as topical drug delivery systems for the treatment of this pathology due to their suitable physicochemical characteristics and enhanced skin penetration ability for deep dermal delivery. Our in vitro data show that the skin application of paclitaxel-loaded ethosomes® improved the permeation of paclitaxel in a stratum corneum-epidermis membrane model and increased its anti-proliferative activity in a squamous cell carcinoma model as compared to the free drug. The results obtained encouraged the use of the paclitaxel-loaded ethosomes® as the formulation for the potential treatment of squamous cell carcinoma, a malignant transformation of actinic keratoses. PMID:22414731

  10. Bladder papillary urothelial neoplasm of low malignant potential in Chinese: a clinical and pathological analysis

    PubMed Central

    Zhang, Xin-Ke; Wang, Ying-Ying; Chen, Jie-Wei; Qin, Tao

    2015-01-01

    Papillary urothelial neoplasm of low malignant potential (PUNLMP) had the incidence of low and definitive recurrence. Therefore, few studies showed that the relationship between pathological factors and the prognosis of patients with PUNLMP. The aim of this study assessed the linkage of pathological factors and prognosis of patients with PUNLMP including the presence or absence of mitoses and the thickness of urothelium. A retrospective analysis of 71 patients with PUNLMP was enrolled between January 2007 and June 2013. The clinicopathological factors consisting of tumor diameter, multifocality, the presence or absence of mitoses and cell thickness of urothelium were retrieved, Log-rank test and Cox proportional hazards regression models were used for univariate and multivariate analyses to evaluate the associations of these factors with recurrence-free survival (RFS) and progression-free survival (PFS).The incidence of recurrence and progression for PUNLMP was 19.7% and 16.9%, respectively. Patients with grade progression represented 85.7% in the recurrent patients. No patients had stage progression and no cases died from invasive urothelial carcinoma. Univariate analysis showed that the presence of mitoses, tumor diameter greater than or equal to 0.8 cm, multifocality were significantly correlated with worse RFS (P < 0.05) and PFS (P < 0.05). Multivariate analysis demonstrated that the presence of mitoses, tumor multifocality were significantly independent biomarkers for worse RFS (P < 0.05) and PFS (P < 0.05). Although the rare and infrequent mitoses were found for PUNLMP, the presence of mitoses and tumor multifocality were still the independent and poor predictors for the prognosis of PUNLMP. In addition, once the PUNLMP appeared to the recurrence, the inevitable grade progression could be determined, herein, long-term follow-up was necessary to be warranted, especially for patients with multiple lesions and the presence of mitoses. PMID:26191263

  11. Bladder papillary urothelial neoplasm of low malignant potential in Chinese: a clinical and pathological analysis.

    PubMed

    Zhang, Xin-Ke; Wang, Ying-Ying; Chen, Jie-Wei; Qin, Tao

    2015-01-01

    Papillary urothelial neoplasm of low malignant potential (PUNLMP) had the incidence of low and definitive recurrence. Therefore, few studies showed that the relationship between pathological factors and the prognosis of patients with PUNLMP. The aim of this study assessed the linkage of pathological factors and prognosis of patients with PUNLMP including the presence or absence of mitoses and the thickness of urothelium. A retrospective analysis of 71 patients with PUNLMP was enrolled between January 2007 and June 2013. The clinicopathological factors consisting of tumor diameter, multifocality, the presence or absence of mitoses and cell thickness of urothelium were retrieved, Log-rank test and Cox proportional hazards regression models were used for univariate and multivariate analyses to evaluate the associations of these factors with recurrence-free survival (RFS) and progression-free survival (PFS).The incidence of recurrence and progression for PUNLMP was 19.7% and 16.9%, respectively. Patients with grade progression represented 85.7% in the recurrent patients. No patients had stage progression and no cases died from invasive urothelial carcinoma. Univariate analysis showed that the presence of mitoses, tumor diameter greater than or equal to 0.8 cm, multifocality were significantly correlated with worse RFS (P<0.05) and PFS (P<0.05). Multivariate analysis demonstrated that the presence of mitoses, tumor multifocality were significantly independent biomarkers for worse RFS (P<0.05) and PFS (P<0.05). Although the rare and infrequent mitoses were found for PUNLMP, the presence of mitoses and tumor multifocality were still the independent and poor predictors for the prognosis of PUNLMP. In addition, once the PUNLMP appeared to the recurrence, the inevitable grade progression could be determined, herein, long-term follow-up was necessary to be warranted, especially for patients with multiple lesions and the presence of mitoses.

  12. Oral health technicians in Brazilian primary health care: potentials and constraints.

    PubMed

    Aguiar, Dulce Maria Lucena de; Tomita, Nilce Emy; Machado, Maria de Fátima Antero Sousa; Martins, Cleide Lavieri; Frazão, Paulo

    2014-07-01

    Different perspectives on the role of mid-level workers in health care might represent a constraint to health policies. This study aimed to investigate how different agents view the participation of oral health technicians in direct activities of oral healthcare with the goal of understanding the related symbolic dispositions. Theoretical assumptions related to inter-professional collaboration and conflicts in the field of healthcare were used for this analysis. A researcher conducted 24 in-depth interviews with general dental practitioners, oral health technicians and local managers. The concepts of Pierre Bourdieu supported the data interpretation. The results indicated inter-professional relations marked by collaboration and conflict that reflect an action space related to different perspectives of primary care delivery. They also unveiled the symbolic devices related to the participation of oral health technicians that represent a constraint to the implementation of oral health policy, thus reducing the potential of primary health care in Brazil. PMID:25166951

  13. Oral health technicians in Brazilian primary health care: potentials and constraints.

    PubMed

    Aguiar, Dulce Maria Lucena de; Tomita, Nilce Emy; Machado, Maria de Fátima Antero Sousa; Martins, Cleide Lavieri; Frazão, Paulo

    2014-07-01

    Different perspectives on the role of mid-level workers in health care might represent a constraint to health policies. This study aimed to investigate how different agents view the participation of oral health technicians in direct activities of oral healthcare with the goal of understanding the related symbolic dispositions. Theoretical assumptions related to inter-professional collaboration and conflicts in the field of healthcare were used for this analysis. A researcher conducted 24 in-depth interviews with general dental practitioners, oral health technicians and local managers. The concepts of Pierre Bourdieu supported the data interpretation. The results indicated inter-professional relations marked by collaboration and conflict that reflect an action space related to different perspectives of primary care delivery. They also unveiled the symbolic devices related to the participation of oral health technicians that represent a constraint to the implementation of oral health policy, thus reducing the potential of primary health care in Brazil.

  14. Breast lesions of uncertain malignant nature and limited metastatic potential: Proposals to improve their recognition and clinical management

    PubMed Central

    Rakha, Emad A.; Badve, Sunil; Eusebi, Vincenzo; Reis-Filho, Jorge S.; Fox, Stephen B.; Dabbs, David J.; Decker, Thomas; Hodi, Zsolt; Ichihara, Shu; Lee, Andrew HS.; Palacios, José; Richardson, Andrea L.; Vincent-Salomon, Anne; Schmitt, Fernando C.; Tan, Puay-Hoon; Tse, Gary M.; Ellis, Ian O.

    2016-01-01

    Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are traditionally classified into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey-zone between benign and malignant as their behaviour cannot be predicted reliably. Defined pathological categorisation of such lesions is challenging and for some entities is recognised to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over-treatment or under-treatment. The rarity of these lesions makes acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification, behaviour and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential such as low-grade adenosquamous carcinoma, low-grade fibromatosis-like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions remain of uncertain malignant nature such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of 1) breast lesions of uncertain malignant nature and 2) breast lesions of limited metastatic potential, are proposed with details of which histological entities could be included in each category, and their management implications are discussed. PMID:26348644

  15. Breast lesions of uncertain malignant nature and limited metastatic potential: proposals to improve their recognition and clinical management.

    PubMed

    Rakha, Emad A; Badve, Sunil; Eusebi, Vincenzo; Reis-Filho, Jorge S; Fox, Stephen B; Dabbs, David J; Decker, Thomas; Hodi, Zsolt; Ichihara, Shu; Lee, Andrew H S; Palacios, José; Richardson, Andrea L; Vincent-Salomon, Anne; Schmitt, Fernando C; Tan, Puay-Hoon; Tse, Gary M; Ellis, Ian O

    2016-01-01

    Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are classified traditionally into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey zone between benign and malignant, as their behaviour cannot be predicted reliably. Defined pathological categorization of such lesions is challenging, and for some entities is recognized to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over- or undertreatment. The rarity of these lesions makes the acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision-making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification and behaviour, and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential, such as low-grade adenosquamous carcinoma, low-grade fibromatosis-like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions of uncertain malignant nature remain, such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of (1) breast lesions of uncertain malignant nature and (2) breast lesions of limited metastatic potential are proposed with details of which histological entities could be included in each category, and their management implications are discussed.

  16. Malignant Potential of Murine Stromal Cells after Transplantation of Human Tumors into Nude Mice

    NASA Astrophysics Data System (ADS)

    Goldenberg, David M.; Pavia, Rose A.

    1981-04-01

    Human malignant cancer tumors grafted into nude mice produce tumors containing both human cancer cells and the host's stromal cells. After short-term propagation of these tumors in vitro, the murine mesenchymal cells appear transformed and are tumorigenic in nude mice. However, established human cancer cell lines fail to similarly alter adjacent murine stromal cells when used to produce tumors in nude mice. These experiments suggest that cancer cells may recruit normal cells to become malignant, qualifying the view of the clonal (unicellular) origin of cancer.

  17. Combination therapy of potential gene to enhance oral cancer therapeutic effect

    NASA Astrophysics Data System (ADS)

    Yeh, Chia-Hsien; Hsu, Yih-Chih

    2015-03-01

    The epidermal growth factor receptor (EGFR) over-regulation related to uncontrolled cell division and promotes progression in tumor. Over-expression of human epidermal growth factor receptor (EGFR) has been detected in oral cancer cells. EGFR-targeting agents are potential therapeutic modalities for treating oral cancer based on our in vitro study. Liposome nanotechnology is used to encapsulate siRNA and were modified with target ligand to receptors on the surface of tumor cells. We used EGFR siRNA to treat oral cancer in vitro.

  18. Precancerous lesions of oral mucosa

    PubMed Central

    Yardimci, Gurkan; Kutlubay, Zekayi; Engin, Burhan; Tuzun, Yalcin

    2014-01-01

    Precancerous lesions of oral mucosa, known as potentially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibrosis, and oral erythroplakia are the most common oral mucosal diseases that have a very high malignant transformation rate. Oral lichen planus is one of the potentially malignant disorders that may be seen in six different subtypes including papular, reticular, plaque-like, atrophic, erosive, and bullous type, clinically. Atrophic and erosive subtypes have the greater increased malignant transformation risk compared to another subtypes. Although there are various etiological studies, the etiology of almost all these diseases is not fully understood. Geographically, etiologic factors may vary. The most frequently reported possible factors are tobacco use, alcohol drinking, chewing of betel quid containing areca nut, and solar rays. Early diagnosis is very important and can be lifesaving, because in late stages, they may be progressed to severe dysplasia and even carcinoma in situ and/or squamous cell carcinoma. For most diseases, treatment results are not satisfactory in spite of miscellaneous therapies. While at the forefront of surgical intervention, topical and systemic treatment alternatives such as corticosteroids, calcineurin inhibitors, and retinoids are widely used. PMID:25516862

  19. Global acetylation and methylation changes predict papillary urothelial neoplasia of low malignant potential recurrence

    PubMed Central

    Mazzucchelli, R.; Scarpelli, M.; Lopez-Beltran, A.; Cheng, L.; Bartels, H.; Bartels, P. H.; Alberts, D. S.; Montironi, R.

    2014-01-01

    Papillary urothelial neoplasia of low malignant potential (PUNLMP) recurs in approximately 35% of patients. Conventional histopathological assessment does not distinguish non-recurrent from recurrent PUNLMP. The aim of the study was to explore the differences in global histone acetylation and global DNA methylation between non-recurrent and recurrent PUNLMP. Acetylated histone H3 lysine 9 (AcH3K9) and 5-methylcytosine (5MeC) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). The total optical density of the nuclear staining was measured photometrically in at least 40 nuclei separately for the basal, intermediate and luminal positions in each case. Concerning the total optical density values for both acetylation and methylation, a decrease in staining is observed from non-recurrent PUNLMP to recurrent PUNLMP, at all nuclear locations. For acetylation the mean value in non-recurrent. PUNLMP, intermediate between NU and UC, is closer to the former than to latter. The mean value in recurrent PUNLMP is closer to UC than to NU. In NU, non-recurrent and recurrent PUNLMP the acetylation to methylation ratio decreased from the nuclei in basal position to those in the surface, the average for the above groups being 1.491, 1.611 and 1.746, respectively. Setting the observed values for NU at each sampling location to unity, acetylation shows a steady decrease, the percentages of changes in this nuclear location compared to NU being − 5% in non-recurrent PUNLMP, − 15% in recurrent PUNLMP and − 24% in UC. Concerning methylation, there is slight increase in non-recurrent PUNLMP (+ 5%), a decrease in recurrent PUNLMP (− 19%) followed by a sharp rise for the UC (+ 61%). In conclusion there are differences in global histone acetylation and DNA methylation patterns between non-recurrent and recurrent PUNLMP. Further studies

  20. Risk, Outcomes, and Costs of Radiation-Induced Oral Mucositis Among Patients With Head-and-Neck Malignancies

    SciTech Connect

    Elting, Linda S. . E-mail: lelting@mdanderson.org; Cooksley, Catherine D.; Chambers, Mark S.; Garden, Adam S.

    2007-07-15

    Purpose: To study the risk, outcomes, and costs of radiation-induced oral mucositis (OM) among patients receiving radiotherapy (RT) to head and neck primary cancers. Methods and Materials: A retrospective cohort consisting of 204 consecutive head-and-neck cancer patients who received RT with or without chemotherapy during 2002 was formed; their records were reviewed for clinical and resource use information. Patients who had received prior therapy, had second primary cancers, or received palliative radiation therapy were excluded. The risk of OM was analyzed by multiple variable logistic regression. The cost of care was computed from the provider's perspective in 2006 U.S. dollars and compared among patients with and without OM. Results: Oral mucositis occurred in 91% of patients; in 66% it was severe (Grade 3-4). Oral mucositis was more common among patients with oral cavity or oropharynx primaries (odds ratio [OR], 44.5; 95% confidence interval [CI], 5.2 to >100; p < 0.001), those who received chemotherapy (OR = 7.8; 95% CI, 1.5-41.6; p 0.02), and those who were treated with altered fractionation schedules (OR 6.3; 95% CI, 1.1-35.1; p = 0.03). Patients with OM were significantly more likely to have severe pain (54% vs. 6%; p < 0.001) and a weight loss of {>=}5% (60% vs. 17%; p < 0.001). Oral mucositis was associated with an incremental cost of $1700-$6000, depending on the grade. Conclusions: Head-and-neck RT causes OM in virtually all patients. Oral mucositis is associated with severe pain, significant weight loss, increased resource use, and excess cost. Preventive strategies are needed.

  1. Oral leukoplakia: a clinicopathological review.

    PubMed

    van der Waal, I; Schepman, K P; van der Meij, E H; Smeele, L E

    1997-09-01

    Leukoplakia is the most common premalignant or potentially malignant lesion of the oral mucosa. It seems preferable to use the term leukoplakia as a clinical term only. When a biopsy is taken, the term leukoplakia should be replaced by the diagnosis obtained histologically. The annual percentage of malignant transformation varies in different parts of the world, probably as a result of differences in tobacco and dietary habits. Although epithelial dysplasia is an important predictive factor of malignant transformation, it should be realized that not all dysplastic lesions will become malignant. On the other hand non-dysplastic lesions may become malignant as well. In some parts of the world the tongue and the floor of the mouth can be considered to be high-risk sites with regard to malignant transformation of leukoplakia, while this does not have to be the case in other parts of the world. The cessation of tobacco habits, being the most common known aetiological factor of oral leukoplakia, has been shown to be an effective measure with regard to the incidence of leukoplakia and, thereby, the incidence of oral cancer as well. Screening for oral precancer may be indicated in individuals at risk.

  2. A Perceptuomotor and Oral Language Program for Children Identified as Potential Failures.

    ERIC Educational Resources Information Center

    Weimer, Wayne Robert

    This study sought to determine whether the de Hirsch Predictive Index Tests would accurately identify children who were potential failures in school. The study also investigated whether a perceptual-motor and oral language program would aid those children identified as potential failures. The Predictive Index Tests were administered to 645 first…

  3. 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

    ARIYOSHI, YASUNORI; SHIMAHARA, MASASHI; KIMURA, YOSHIHIRO; ITO, YUICHI; SHIMAHARA, TAKESHI; MIYATAKE, SHIN-ICHI; KAWABATA, SHINJI

    2011-01-01

    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. PMID:22866098

  4. Oral infectious diseases: a potential risk factor for HIV virus recrudescence?

    PubMed Central

    González, OA; Ebersole, JL; Huang, CB

    2014-01-01

    As the highly active antiretroviral therapy (HAART) has transitioned human immunodeficiency virus (HIV) infection into a ‘chronic disease’ management strategy, there is growing evidence that infection with non-HIV pathogens in HIV+ patients may have important public health implications in undermining HAART success and acquired immunodeficiency syndrome progression. Several bacterial and host cell products during infections with non-HIV pathogens have shown the capacity to regulate HIV replication in latently infected cells. A high prevalence of oral infections caused by bacteria, viruses and fungi has been described in HIV+ patients, including periodontal disease. The oral cavity appears to be a site of HIV pathogenesis and potential reservoir for the disease as HIV RNA and DNA forms are present in saliva as well as in gingival crevicular fluid, and oral epithelial cells are susceptible to either cell free or cell-associated HIV infection. The clinical and biological bases of potential associations between chronic oral inflammatory disorders, such as periodontal disease, and exacerbation of HIV viraemia have received little attention. This review attempts to evaluate the current understanding of HIV reactivation as a result of co-infection and/or inflammation induced by non-HIV pathogens in HIV-infected patients, and presents a hypothetic model about the potential role of periodontitis as a global oral infection that potentially contributes to HIV recrudescence. PMID:19364391

  5. Oral infectious diseases: a potential risk factor for HIV virus recrudescence?

    PubMed

    González, O A; Ebersole, J L; Huang, C B

    2009-07-01

    As the highly active antiretroviral therapy (HAART) has transitioned human immunodeficiency virus (HIV) infection into a 'chronic disease' management strategy, there is growing evidence that infection with non-HIV pathogens in HIV+ patients may have important public health implications in undermining HAART success and acquired immunodeficiency syndrome progression. Several bacterial and host cell products during infections with non-HIV pathogens have shown the capacity to regulate HIV replication in latently infected cells. A high prevalence of oral infections caused by bacteria, viruses and fungi has been described in HIV+ patients, including periodontal disease. The oral cavity appears to be a site of HIV pathogenesis and potential reservoir for the disease as HIV RNA and DNA forms are present in saliva as well as in gingival crevicular fluid, and oral epithelial cells are susceptible to either cell free or cell-associated HIV infection. The clinical and biological bases of potential associations between chronic oral inflammatory disorders, such as periodontal disease, and exacerbation of HIV viraemia have received little attention. This review attempts to evaluate the current understanding of HIV reactivation as a result of co-infection and/or inflammation induced by non-HIV pathogens in HIV-infected patients, and presents a hypothetic model about the potential role of periodontitis as a global oral infection that potentially contributes to HIV recrudescence. PMID:19364391

  6. Hypoxia inducible factor: a potential prognostic biomarker in oral squamous cell carcinoma.

    PubMed

    Qian, Jiang; Wenguang, Xu; Zhiyong, Wang; Yuntao, Zou; Wei, Han

    2016-08-01

    Oral squamous cell carcinoma (OSCC) is the most common oral cancer. Hypoxia inducible factor (HIF) is involved in many malignant tumors' growth and metastasis and upregulated by hypoxia, including oral cancer. Many studies have studied about the prognostic value of HIF expression in OSCC; however, they do not get the consistent results. Therefore, this study explored the correlation between the HIF expression and the prognosis of OSCC. It conducted a meta-analysis of relevant publications searched in the Web of Science, PubMed, and ISI Web of Knowledge databases. Totally, this study identified 12 relevant articles reporting a total of 1112 patients. This analysis revealed a significant association between increased risk of mortality (RR = 1.20; 95 % CI 0.74-1.95; I (2) 85.4 %) and overexpression of HIFs. Furthermore, different HIF isoforms were associated with overall survival [HIF-1α (RR = 1.18; 95 % CI 0.66-2.11; I (2) 87.2 %) and HIF-2α (RR = 1.40; 95 % CI 0.93-2.09; I(2) 0.0 %)]. These results show that overexpression of HIFs, regardless of whether the HIF-1α or HIF-2α isoforms are overexpressed is significantly associated with increased risk of mortality in OSCC patients. In this study, the funnel is symmetric, suggesting existed no publication bias.

  7. Potential implications of adjuvant endocrine therapy for the oral health of postmenopausal women with breast cancer

    PubMed Central

    Taichman, L. Susan; Havens, Aaron M.

    2012-01-01

    Current adjuvant treatment modalities for breast cancer that express the estrogen receptor or progesterone receptor include adjuvant anti-estrogen therapies, and tamoxifen and aromatase inhibitors. Bone, including the jaw, is an endocrine-sensitive organ, as are other oral structures. This review examines the potential links between adjuvant anti-estrogen treatments in postmenopausal women with hormone receptor positive breast cancer and oral health. A search of PubMed, EMBASE, CENTRAL, and the Web of Knowledge was conducted using combinations of key terms “breast,” “cancer,” “neoplasm,” “Tamoxifen,” “Aromatase Inhibitor,” “chemotherapy,” “hormone therapy,” “alveolar bone loss,” “postmenopausal bone loss,” “estrogen,” “SERM,” “hormone replacement therapy,” and “quality of life.” We selected articles published in peer-reviewed journals in the English. The authors found no studies reporting on periodontal diseases, alveolar bone loss, oral health, or oral health-related quality of life in association with anti-estrogen breast cancer treatments in postmenopausal women. Periodontal diseases, alveolar bone density, tooth loss, and conditions of the soft tissues of the mouth have all been associated with menopausal status supporting the hypothesis that the soft tissues and bone of the oral cavity could be negatively affected by anti-estrogen therapy. As a conclusion, the impact of adjuvant endocrine breast cancer therapy on the oral health of postmenopausal women is undefined. The structures of the oral cavity are influenced by estrogen; therefore, anti-estrogen therapies may carry the risk of oral toxicities. Oral health care for breast cancer patients is an important but understudied aspect of cancer survivorship. PMID:22986813

  8. Anisi stellati fructus extract attenuates the in vitro and in vivo metastatic and angiogenic potential of malignant cancer cells by downregulating proteolytic activity and pro-angiogenic factors.

    PubMed

    Kim, Aeyung; Im, Minju; Ma, Jin Yeul

    2014-11-01

    Anisi stellati fructus (ASF), commonly known as star anise, has long been used as a traditional Chinese medicine to treat inflammation, nervousness, insomnia and pain. In recent studies, it has been demonstrated that ASF possesses anti-bacterial, anti-fungal and anti-oxidant activities, as well as exhibits inhibitory effects on capillary‑like tube formation in human umbilical vein endothelial cells (HUVECs). However, the effects of ASF extract on the metastatic potential of malignant tumor cells have not been examined. In this study, we found that daily oral administration of ASF (50 mg/kg) remarkably reduced the number of pulmonary metastatic colonies of B16F10 cells in C57BL/6J mice with no observed systemic toxicity. In an in vitro system, ASF inhibited metastatic properties, including anchorage‑independent colony formation, migration and invasion. Upon phorbol 12-myristate 13-acetate (PMA) stimulation, the mRNA levels of matrix metalloproteinases (MMPs) -9, -13, -14 and urokinase plasminogen activator (uPA) decreased in a dose-dependent manner with ASF treatment. Gelatinase, type I collagenase, and uPA activities were also suppressed efficiently by ASF treatment. In response to PMA, NF-κB and AP-1 activation as well as p38 phosphorylation, which are crucial for MMP activation, were significantly decreased by ASF. In particular, ASF considerably inhibited tumor-induced HUVEC migration and tube formation and suppressed in vivo tumor-induced angiogenesis via a reduction of pro-angiogenic factors in tumors. These results collectively indicate that ASF might be useful in the management of metastatic malignant tumors. PMID:25176510

  9. [Combined use of irradiation and DNA tumor vaccine to treat canine oral malignant melanoma: a pilot study].

    PubMed

    Herzog, A; Buchholz, J; Ruess-Melzer, K; Lang, J; Kaser-Hotz, B

    2013-02-01

    Melanoma is the most common oral tumor in dogs, characterized by rapid growth, local invasion, and high metastatic rate. The goal of this study was to evaluate the combination of radiation therapy and DNA tumor vaccine. We hypothesized, that the concurrent use would not increase toxicity. Nine dogs with oral melanoma were treated with 4 fractions of 8 Gray at 7-day intervals. The vaccine was given 4 times every 14 days, beginning at the first radiation fraction. Local acute radiation toxicities were assessed according to the VRTOG toxicity scoring scheme over a time period of 7 weeks. In none of the evaluated dogs, mucositis, dermatitis and conjunctivitis exceeded grade 2. In 3 dogs mild fever, lethargy, and local swelling at the injection site were seen after vaccine application. In conclusion, the concurrent administration of radiation therapy and vaccine was well tolerated in all dogs. PMID:23385072

  10. Deep vein thrombosis and changes in coagulation and fibrinolysis after gynaecological operations in Chinese: the effect of oral contraceptives and malignant disease.

    PubMed

    Tso, S C; Wong, V; Chan, V; Chan, T K; Ma, H K; Todd, D

    1980-12-01

    Of 154 Chinese patients who underwent gynaecological operations, four showed a positive 125I fibrinogen leg scan for venous thrombosis, and overall incidence of 2 . 6%. In those who were on oral contraceptives and had major pelvic surgery for benign conditions, the incidence was 10 . 5%; in those who had Wertheim hysterectomy for carcinoma of cervix, it was 6 . 7%. This confirms the rarity of post-operative thromboembolism in the Chinese. Fragment E showed a biphasic rise after major operation due to tissue injury and venous thrombosis. In patients with malignancy, the postoperative 'fibrinolytic shutdown', represented by decreased plasminogen activator together with increased alpha 1 antitrypsin and C1- inhibitor levels, was more marked. In addition, alpha 2 macroglobulin level was lower and fell significantly after operation. In patients on oral contraceptives, fragment E levels were higher after surgery and there was no decrease in plasminogen activator levels. Antithrombin III levels did not fall except in three of the four patients with venous thrombosis. A marked increase in fragment E level and a decrease in antithrombin III level might be useful diagnostic markers for postoperative venous thrombosis.

  11. A retrospective review of outcome and survival following surgery and adjuvant xenogeneic DNA vaccination in 32 dogs with oral malignant melanoma

    PubMed Central

    TREGGIARI, Elisabetta; GRANT, Jessica Pauline; NORTH, Susan Margaret

    2016-01-01

    A xenogeneic DNA vaccination has been licensed for use in dogs with locally controlled stage II and III oral malignant melanoma (OMM). At present, there are limited outcome data for dogs with OMM treated with surgery and immunotherapy. The aim of this study is to retrospectively review the outcome and survival of 32 dogs affected by OMM that were treated with a combination of surgery and the xenogeneic DNA vaccination (with the addition of radiotherapy in some cases) and to determine the influence of surgical margins and delay in receiving vaccination. The overall median survival time (MST) was 335 days (95% CI: 301–540 days), and the overall median progression-free survival (PFS) was 160 days (mean 182 days, 95% CI: 132–232 days). Stage, completeness of surgical margins and delay in administration of the vaccine did not appear to statistically influence survival or PFS, although these results may reflect the low statistical power of the study due to small numbers. Further studies are required to assess whether the addition of any adjuvant treatment to surgery, including immunotherapy, is able to significantly prolong survival in cases of canine oral melanoma. PMID:26781703

  12. Primary malignant melanoma

    PubMed Central

    Mısır, A. Ferhat; Durmuşlar, Mustafa C.; Zerener, Tamer; Gün, Banu D.

    2016-01-01

    Malignant melanomas (MM) of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at the level of the hard palate and gingiva. Early diagnosis and treatment are important for reducing morbidity. Malignant melanoma cells stain positively with antibodies to human melanoma black 45, S-100 protein, and vimentin; therefore, immunohistochemistry can play an important role in evaluating the depth of invasion and the location of metastases. A 76-year-old man developed an oral malignant melanoma, which was originally diagnosed as a bluish reactive denture hyperplasia caused by an ill-fitting lower denture. The tumor was removed surgically, and histopathological examination revealed a nodular-type MM. There was no evidence of recurrence over a 4-year follow-up period. PMID:27052289

  13. Potential of boron neutron capture therapy (BNCT) for malignant peripheral nerve sheath tumors (MPNST).

    PubMed

    Fujimoto, Takuya; Andoh, Tooru; Sudo, Tamotsu; Fujita, Ikuo; Fukase, Naomasa; Takeuchi, Tamotsu; Sonobe, Hiroshi; Inoue, Masayoshi; Hirose, Tkanori; Sakuma, Toshiko; Moritake, Hiroshi; Sugimoto, Tohru; Kawamoto, Teruya; Fukumori, Yoshinobu; Yamamoto, Satomi; Atagi, Shinji; Sakurai, Yoshinori; Kurosaka, Masahiro; Ono, Koji; Ichikawa, Hideki; Suzuki, Minoru

    2015-12-01

    Malignant peripheral nerve sheath tumors (MPNST) are relatively rare neoplasms with poor prognosis. At present there is no effective treatment for MPNST other than surgical resection. Nonetheless, the anti-tumor effect of boron neutron capture therapy (BNCT) was recently demonstrated in two patients with MPNST. Subsequently, tumor-bearing nude mice subcutaneously transplanted with a human MPNST cell line were injected with p-borono-L-phenylalanine (L-BPA) and subjected to BNCT. Pathological studies then revealed that the MPNST cells were selectively destroyed by BNCT.

  14. [Carcinoma with low malignant potential (borderline tumor) of the ovary: immunomorphology and clinical aspects].

    PubMed

    Neunteufel, W; Gitsch, G; Schieder, K; Kölbl, H; Breitenecker, G

    1989-01-01

    Four of 28 patients with borderline tumors of the ovary died of intercurrent disease. Twenty-four are alive without clinical evidence of disease, despite the fact that six of them were stage III; joined with the invasive carcinomas they would distort the survival rates. The development of monoclonal antibodies specific to borderline tumors could improve the value of immunohistochemistry in the diagnosis of borderline tumors. Our results show that the rates of expression of CA 125, CA 19-9, and CEA indicate that borderline tumors are an independent group between benign and malignant ovarian tumors.

  15. Lenvatinib and Capecitabine in Patients With Advanced Malignancies

    ClinicalTrials.gov

    2016-09-23

    Advanced Cancer; Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract

  16. Potential use of oral fluid samples for serological diagnosis of African swine fever.

    PubMed

    Mur, Lina; Gallardo, Carmina; Soler, Alejandro; Zimmermman, Jeffrey; Pelayo, Virginia; Nieto, Raquel; Sánchez-Vizcaíno, José Manuel; Arias, Marisa

    2013-07-26

    African swine fever (ASF) is a complex, highly lethal, notifiable disease of swine. ASF is wide-spread in sub-Saharan Africa and East European countries and there is presently a great risk of spread to neighboring countries. Since there is no vaccine for ASF virus (ASFV), control is based on rapid and early detection of the disease via surveillance. This approach requires collecting blood samples from large number of animals. Laborious and expensive of itself, this process also presents an additional risk because ASFV is present at high concentrations in the blood. The objective of this study was to initiate studies into the potential use of oral fluid as an alternative to serum for ASF diagnosis, for latter studying its possible use in surveillance and control programs. To this end, oral fluid samples collected at different times post infection from eight pigs experimentally inoculated with an attenuated ASFV were assayed using modified protocols of the two validated serological techniques, the enzyme-immune-liked assay (ELISA) and immunoperoxidase technique (IPT). Antibodies against ASFV were detected in oral fluid samples of all animals from early post infection through the end of the experiment by ELISA and IPT. These results confirmed the presence of ASFV antibodies in swine oral fluids samples, the possibility of an oral fluid-based approach in ASF diagnosis and, potentially in ASF surveillance.

  17. Oral epithelioid hemangioendothelioma

    PubMed Central

    Bhattacharya, Preeti Tomar; Guledgud, Mahima V.; Patil, Karthikeya

    2015-01-01

    Epithelioid hemangioendothelioma (HE) is an intermediate malignant potential vascular neoplasm with uncertain clinical behavior, wide variations in microscopic findings, and prognosis. According to the World Health Organization (2002) classification, epithelioid HE has been considered under malignant tumors which rarely metastasize. The epithelioid variant, the most aggressive one, has similar gender predilection and sporadic occurrence in children. The patients usually present with an asymptomatic oral mass whereas few cases may report with the painful bleeding lesion. We attempt to present a case in an adolescent male with previously never described biological behavior, diverse histopathological features, and immunohistochemistry findings. PMID:26681871

  18. It's Story Time!: Exploring the Potential of Multimodality in Oral Storytelling to Support Children's Vocabulary Learning

    ERIC Educational Resources Information Center

    Lwin, Soe Marlar

    2016-01-01

    Although many studies have been done on the benefits of parent/teacher-child interactions during shared storybook reading or read'aloud sessions, very few have examined the potential of professional storytellers' oral discourse to support children's vocabulary learning. In those storytelling sessions conducted by professional storytellers, the…

  19. Clinicopathologic Review of 31 Cases of Solid Pseudopapillary Pancreatic Tumors: Can We Use the Scoring System of Microscopic Features for Suggesting Clinically Malignant Potential?

    PubMed

    Kim, Jang-Hee; Lee, Jae-Myeong

    2016-04-01

    A solid pseudopapillary tumor (SPT) is a pancreatic neoplasm of low malignant potential. The potentially malignant pathologic features of SPTs were regarded as angioinvasion, perineural invasion, deep invasion of the surrounding acinar tissue, and nuclear pleomorphism. We retrospectively reviewed 31 cases of SPTs (25 female and 6 male patients, with an average age of 35 ± 14 years). The mean follow-up period was 132.0 ± 55.9 months. To evaluate the clinical impact of above pathological parameters, we analyzed their correlation with actually observed clinical malignancy. In three cases, the SPTs were clearly clinically malignant: one patient had recurrences three times, one showed lymph node metastases, and one deep soft tissue invasion around the gastroduodenal artery. Tumor infiltration to the peripancreatic soft tissue was observed in 17 cases (54.8%). The pathologic features considered suggestive of malignant potential were angioinvasion (25.8%), perineural invasion (6.5%), presence of mitosis in 10 high-power fields (16.1%), and moderate nuclear pleomorphism (19.4%). The presence of at least three of these features was not correlated with clinically confirmed malignant behavior (P = 0.570). Microscopic pathologic features of SPTs cannot be reliably associated with aggressive clinical behavior. Moreover, the absence of these microscopic features cannot exclude clinical malignancy. PMID:27097622

  20. TNF-related apoptosis-inducing ligand (TRAIL): a potential candidate for combined treatment of hematological malignancies.

    PubMed

    Secchiero, Paola; Vaccarezza, Mauro; Gonelli, Arianna; Zauli, Giorgio

    2004-01-01

    TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF gene superfamily, which induces apoptosis through engagement of death receptors. TRAIL is unusual as compared to the other cytokines of this family, as it interacts with a complex system of receptors consisting of two pro-apoptotic death receptors (TRAIL-R1 and TRAIL-R2) and three decoy receptors (TRAIL-R3, TRAIL-R4 and osteoprotegerin). Moreover, with respect to other members of the TNF superfamily, such as CD95L and TNF-alpha, TRAIL has generated great interest as a potential tumor-specific cancer therapeutic because as a stable soluble trimer it selectively induces apoptosis in many transformed cells but not in normal cells. Of note, TRAIL cytotoxicity is at least partially independent of the major systems involved in resistance to chemotherapy, such as p53 wild-type function and multidrug resistance (MDR) genes. Since one fundamental problem of most cancers is the development of multiple mechanisms of resistance, which progressively reduce or suppress the therapeutic efficacy of conventional chemotherapy, new therapeutic approaches that either restore the pro-apoptotic activity of chemotherapeutic drugs or by-pass the mechanisms of resistance are highly desirable. This review will focus on the potential of TRAIL for its application in the therapy of hematological malignancies, used either alone or in combination with chemotherapy. The scenario emerging from the literature is that the treatment and management of hematological malignancies will require the rational combination of TRAIL plus conventional or new drugs in a regimen that would optimize the anti-neoplastic activity in malignant cells resistant to chemotherapy through restoration of the pro-apoptotic activity of TRAIL. PMID:15579063

  1. Surface display of Clonorchis sinensis enolase on Bacillus subtilis spores potentializes an oral vaccine candidate.

    PubMed

    Wang, Xiaoyun; Chen, Wenjun; Tian, Yanli; Mao, Qiang; Lv, Xiaoli; Shang, Mei; Li, Xuerong; Yu, Xinbing; Huang, Yan

    2014-03-10

    Clonorchis sinensis (C. sinensis) infections remain the common public health problem in freshwater fish consumption areas. New effective prevention strategies are still the urgent challenges to control this kind of foodborne infectious disease. The biochemical importance and biological relevance render C. sinensis enolase (Csenolase) as a potential vaccine candidate. In the present study, we constructed Escherichia coli/Bacillus subtilis shuttle genetic engineering system and investigated the potential of Csenolase as an oral vaccine candidate for C. sinensis prevention in different immunization routes. Our results showed that, compared with control groups, both recombinant Csenolase protein and nucleic acid could induce a mixed IgG1/IgG2a immune response when administrated subcutaneously (P<0.001), intraperitoneally (P<0.01) and intramuscularly (P<0.001) with worm reduction rate of 56.29%, 15.38% and 37.42%, respectively. More importantly, Csenolase could be successfully expressed as a fusion protein (55kDa) on B. subtilis spore indicated by immunoblot and immunofluorescence assays. Killed spores triggered reactive Th1/Th2 immune response and exhibited protective efficacy against C. sinensis infection. Csenolase derived oral vaccine conferred worm reduction rate and egg reduction rate at 60.07% (P<0.001) and 80.67% (P<0.001), respectively. The shuttle genetic engineering system facilitated the development of oral vaccine with B. subtilis stably overexpressing target protein. Comparably vaccinal trails with Csenolase in different immunization routes potentialize Csenolase an oral vaccine candidate in C. sinensis prevention.

  2. Evaluating the potential of cubosomal nanoparticles for oral delivery of amphotericin B in treating fungal infection

    PubMed Central

    Yang, Zhiwen; Chen, Meiwan; Yang, Muhua; Chen, Jian; Fang, Weijun; Xu, Ping

    2014-01-01

    The oral administration of amphotericin B (AmB) has a major drawback of poor bioavailability. The aim of this study was to investigate the potential of glyceryl monoolein (GMO) cubosomes as lipid nanocarriers to improve the oral efficacy of AmB. Antifungal efficacy was determined in vivo in rats after oral administration, to investigate its therapeutic use. The human colon adenocarcinoma cell line (Caco-2) was used in vitro to evaluate transport across a model of the intestinal barrier. In vivo antifungal results showed that AmB, loaded in GMO cubosomes, could significantly enhance oral efficacy, compared against Fungizone®, and that during a 2 day course of dosage 10 mg/kg the drug reached effective therapeutic concentrations in renal tissue for treating fungal infections. In the Caco-2 transport studies, GMO cubosomes resulted in a significantly larger amount of AmB being transported into Caco-2 cells, via both clathrin- and caveolae-mediated endocytosis, but not macropinocytosis. These results suggest that GMO cubosomes, as lipid nanovectors, could facilitate the oral delivery of AmB. PMID:24421641

  3. The rationale and potential for the reduction of oral malodour using Streptococcus salivarius probiotics.

    PubMed

    Burton, J P; Chilcott, C N; Tagg, J R

    2005-01-01

    The primary treatment for oral malodour is the reduction of bacterial populations, especially those present on the tongue, by use of a variety of antimicrobial agents or mechanical devices. However, shortly after treatment the problematic bacteria quickly repopulate the tongue and the malodour returns. In our studies, we have used a broadly-active antimicrobial (chlorhexidine) to effect temporary depletion of the oral microbiota and then have attempted to repopulate the tongue surface with Streptococcus salivarius K12, a benign commensal probiotic. The objective of this is to prevent re-establishment of non-desirable bacterial populations and thus help limit the re-occurrence of oral malodour over a prolonged period. In this paper, we discuss why contemporary probiotics are inadequate for treatment of oral malodour and examine the rationale for selection of particular bacterial species for future use in the treatment of this condition. In our preliminary trials of the use of a chlorhexidine rinse followed by strain K12 lozenges, the majority (8/13) of subjects with confirmed halitosis maintained reduced breath levels of volatile sulphur compounds for at least 2 weeks. We conclude that probiotic bacterial strains originally sourced from the indigenous oral microbiotas of healthy humans may have potential application as adjuncts for the prevention and treatment of halitosis. PMID:15752094

  4. Maltose-binding protein is a potential carrier for oral immunizations.

    PubMed

    Bellot, P; Tiels, P; Melkebeek, V; Devriendt, B; Goddeeris, B M; Cox, E

    2013-03-15

    Maltose binding protein (MBP) is often fused to a relevant protein to improve its yield and facilitate its purification, but MBP can also enhance the immunogenicity of the fused proteins. Recent data suggest that MBP may potentiate antigen-presenting functions in immunized animals by providing intrinsic maturation stimuli to dendritic cells through TLR4. The aim of this study was to examine if an MBP-specific immune response can be elicited by oral administration of MBP. Therefore, in a first experiment the MBP specific immune response was analyzed after oral immunization with MBP or MBP+CT to piglets and both the systemic and mucosal immune responses were examined Although no high systemic response was observed in the MBP-group, a local mucosal IgM MBP-specific response in the jejunal Peyer's patches was observed. In the second experiment MBPFedF was orally administered to piglets. A significant systemic response against MBP and a weak response against FedF were found after oral administration of MBPFedF+CT. Also the presence of MBP-specific IgA ASC in the lamina propria indicates that a local intestinal immune response against MBP was induced. Our data suggests that MBP can cross the epithelial barrier reaching the gut-associated lymphoid tissue after oral administration to pigs, which implicates that MBP could act as a carrier and delivery system for fused proteins to target the vaccine antigens to intestinal immune cells. PMID:23078905

  5. Evaluating the potential of cubosomal nanoparticles for oral delivery of amphotericin B in treating fungal infection.

    PubMed

    Yang, Zhiwen; Chen, Meiwan; Yang, Muhua; Chen, Jian; Fang, Weijun; Xu, Ping

    2014-01-01

    The oral administration of amphotericin B (AmB) has a major drawback of poor bioavailability. The aim of this study was to investigate the potential of glyceryl monoolein (GMO) cubosomes as lipid nanocarriers to improve the oral efficacy of AmB. Antifungal efficacy was determined in vivo in rats after oral administration, to investigate its therapeutic use. The human colon adenocarcinoma cell line (Caco-2) was used in vitro to evaluate transport across a model of the intestinal barrier. In vivo antifungal results showed that AmB, loaded in GMO cubosomes, could significantly enhance oral efficacy, compared against Fungizone, and that during a 2 day course of dosage 10 mg/kg the drug reached effective therapeutic concentrations in renal tissue for treating fungal infections. In the Caco-2 transport studies, GMO cubosomes resulted in a significantly larger amount of AmB being transported into Caco-2 cells, via both clathrin- and caveolae-mediated endocytosis, but not macropinocytosis. These results suggest that GMO cubosomes, as lipid nanovectors, could facilitate the oral delivery of AmB.

  6. Increased malignancy of oral squamous cell carcinomas (oscc) is associated with macrophage polarization in regional lymph nodes – an immunohistochemical study

    PubMed Central

    2014-01-01

    Background It is largely accepted that specific immunological parameters in solid malignancies are associated with patient’s prognosis. Recently a correlation of macrophage polarization with histomorphological parameters could also be shown in oral squamous cell carcinoma (oscc). The observed tumor derived peripheral immune tolerance could be associated with the macrophage polarization in regional tumor draining lymph nodes. So far there are no studies analyzing the macrophage polarization in cervical lymph nodes of oscc patients. In the present study we aimed to correlate macrophage polarization in different anatomical lymph node compartments of patients diagnosed with oscc with histopathologic parameters of the primary tumor (T-, N-, L-, V-, Pn-status, grading). Methods Tumor free (n = 37) and metastatic (n = 17) lymph nodes of T1 and T2 oscc patients were processed for immunohistochemistry to detect CD68, CD11c, CD163 and MRC1 positive cells. Samples were digitized using whole slide imaging and the number of cells expressing the aforementioned markers in the region of interest quantitatively analyzed. Results The malignancy of the primary tumor (defined by T-, L-, Pn-status, grading) correlated with the lymph node macrophage polarization. L1 and Pn1 tumor cases displayed a significantly (p < 0.05) decreased M1 and increased M2 polarization in the sinus of the lymph nodes. G3 cases presented a significantly (p < 0.05) increased M2 polarization in the sinus compared to G2 cases. T2 tumors had significantly (p < 0.05) increased M2 polarization in the interfollicular zone of regional lymph nodes compared to T1 tumors. Metastatic and non-metastatic lymph nodes did not differ regarding their macrophage polarization. Conclusions The current study revealed for the first time an influence of oscc on the macrophage polarization in regional lymph nodes. Markers of malignant behavior in the primary tumor were associated with a shift of macrophage

  7. Data from human salivary proteome – A resource of potential biomarkers for oral cancer

    PubMed Central

    Sivadasan, Priya; Kumar Gupta, Manoj; Sathe, Gajanan J.; Balakrishnan, Lavanya; Palit, Priyanka; Gowda, Harsha; Suresh, Amritha; Abraham Kuriakose, Moni; Sirdeshmukh, Ravi

    2015-01-01

    Salivary proteins are an important source for developing marker-based assays for oral cancers. To get an insight into the proteins present in human saliva, we applied multiple strategies involving affinity-based depletion of abundant proteins, fractionation of the resulting proteins or their tryptic peptides followed by LC–MS/MS analysis, using high resolution mass spectrometry. By integrating the protein identifications observed by us with those from similar workflows employed in earlier investigations, we compiled an updated salivary proteome. We have mapped the salivary proteome to the published data on differentially expressed proteins from oral cancer tissues and also for their secretory features using prediction tools, SignalP 4.1, TMHMM 2c and Exocarta. Proteotypic peptides for the subset of proteins implicated in oral cancer and mapped to any two of the prediction tools for secretory potential have been listed. The data here are related to the research article “Human saliva proteome – a resource of potential biomarkers for oral cancer” in the Journal of Proteomics [1]. PMID:26217819

  8. [Galectins in hematological malignancies--role, functions and potential therapeutic targets].

    PubMed

    Wdowiak, Kamil; Spychałowicz, Wojciech; Fajkis, Marcin; Wojnar, Jerzy

    2016-01-01

    Galectins are a family of lectins characterized by an affinity for β-galactosides through the carbohydrate recognition domain (CRD). The extracellular and intracellular presence of Galectins has been described. Their activity and functions are mainly attributed to cell type. The tumor microenviroment is a complex milieu connected with immunosupression, angiogenesis and hypoxic compartments. The studies of interactions between Glycans-Lectins are highly advanced and promising. We are not able to explain the pathogenesis of many diseases only by protein-protein interactions, that is why in these studies is a chance to find a new therapeutic targets. Galectins play a fundametal functions in tumor growth and progression, angiogenesis, adhesion, tumor immune-escape. They are also active in inflammation, fibrosis, organogenesis and immunological functions. The most known Galectin is Gal-3. Depending on the localization Gal-3 may exhibit either pro-apoptotic or anti-apoptotic activity. This publication presents role of Galectins in hematological malignancies and shows potencial prognostoic value and new therapeutic possibilities.

  9. Malignant hyperthermia.

    PubMed Central

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

    1998-01-01

    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. PMID:9538480

  10. CD146 is a novel marker for highly tumorigenic cells and a potential therapeutic target in malignant rhabdoid tumor

    PubMed Central

    Nodomi, S; Umeda, K; Saida, S; Kinehara, T; Hamabata, T; Daifu, T; Kato, I; Hiramatsu, H; Watanabe, K-i; Kuwahara, Y; Iehara, T; Adachi, S; Konishi, E; Nakahata, T; Hosoi, H; Heike, T

    2016-01-01

    Malignant rhabdoid tumor (MRT) is a rare, highly aggressive pediatric malignancy that primarily develops during infancy and early childhood. Despite the existing standard of intensive multimodal therapy, the prognosis of patients with MRT is dismal; therefore, a greater understanding of the biology of this disease is required to establish novel therapies. In this study, we identified a highly tumorigenic sub-population in MRT, based on the expression of CD146 (also known as melanoma cell adhesion molecule), a cell adhesion molecule expressed by neural crest cells and various derivatives. CD146+ cells isolated from four MRT cell lines by cell sorting exhibited enhanced self-renewal and invasive potential in vitro. In a xenograft model using immunodeficient NOD/Shi-scid IL-2Rγ-null mice, purified CD146+ cells obtained from MRT cell lines or a primary tumor exhibited the exclusive ability to form tumors in vivo. Blocking of CD146-related mechanisms, either by short hairpin RNA knockdown or treatment with a polyclonal antibody against CD146, effectively suppressed tumor growth of MRT cells both in vitro and in vivo via induction of apoptosis by inactivating Akt. Furthermore, CD146 positivity in immunohistological analysis of 11 MRT patient samples was associated with poor patient outcomes. These results suggest that CD146 defines a distinct sub-population in MRT with high tumorigenic capacity and that this marker represents a promising therapeutic target. PMID:27041577

  11. Uterine smooth muscle tumors of uncertain malignant potential: analysis of diagnoses and therapies illustrated by two case reports.

    PubMed

    Peeters, N; Hulsbosch, S; Ballaux, F; Baekelandt, J

    2016-01-01

    Uterine smooth muscle tumors of uncertain malignant potential, or STUMP, form a rare group of tumors that fall neither into the benign nor malignant categories. Two cases are reported, describing diagnosis, known prognostic factors, and therapy. In contrast to leiomyomas and leiomyosarcomas, many uncertainties still exist concerning prognosis and postoperative management of STUMP, because of their rarity. Diagnosis is usually not made preoperatively, but by postoperative anatomo-pathological examination. There are histological and immunohistochemical factors that could be associated with a worse prognosis, but scientific evidence is insufficient. Most cases show a low risk of recurrence, although individual risk is unpredictable. Recurrences mostly occur after a long disease-free interval. A conservative approach with strict long-term clinical follow-up is therefore indicated. Further research must be conducted to identify surgical procedures that have a higher risk for recurrence. After a laparoscopy, where the specimen was morcellated, the possibility of peritoneal spread and the difficulty in examining section margins, need to be taken into account. Further treatment therefore needs to be individualized. PMID:27352566

  12. Inhibition of autophagy potentiates pemetrexed and simvastatin-induced apoptotic cell death in malignant mesothelioma and non-small cell lung cancer cells

    PubMed Central

    Jung, Jae-Wan; Kwon, Su-Jin; Park, Do-Sim; Cha, Byong-Ki; Oh, Seon-Hee; Yoon, Kwon-Ha; Jeong, Eun-Taik; Kim, Hak-Ryul

    2015-01-01

    Pemetrexed, a multitarget antifolate used to treat malignant mesothelioma and non-small cell lung cancer (NSCLC), has been shown to stimulate autophagy. In this study, we determined whether autophagy could be induced by pemetrexed and simvastatin cotreatment in malignant mesothelioma and NSCLC cells. Furthermore, we determined whether inhibition of autophagy drives apoptosis in malignant mesothelioma and NSCLC cells. Malignant mesothelioma MSTO-211H and A549 NSCLC cells were treated with pemetrexed and simvastatin alone and in combination to evaluate their effect on autophagy and apoptosis. Cotreatment with pemetrexed and simvastatin induced greater caspase-dependent apoptosis and autophagy than either drug alone in malignant mesothelioma and NSCLC cells. 3-Methyladenine (3-MA), ATG5 siRNA, bafilomycin A, and E64D/pepstatin A enhanced the apoptotic potential of pemetrexed and simvastatin, whereas rapamycin and LY294002 attenuated their induction of caspase-dependent apoptosis. Our data indicate that pemetrexed and simvastatin cotreatment augmented apoptosis and autophagy in malignant mesothelioma and NSCLC cells. Inhibition of pemetrexed and simvastatin-induced autophagy was shown to enhance apoptosis, suggesting that this could be a novel therapeutic strategy against malignant mesothelioma and NSCLC. PMID:26334320

  13. Inhibition of autophagy potentiates pemetrexed and simvastatin-induced apoptotic cell death in malignant mesothelioma and non-small cell lung cancer cells.

    PubMed

    Hwang, Ki-Eun; Kim, Young-Suk; Jung, Jae-Wan; Kwon, Su-Jin; Park, Do-Sim; Cha, Byong-Ki; Oh, Seon-Hee; Yoon, Kwon-Ha; Jeong, Eun-Taik; Kim, Hak-Ryul

    2015-10-01

    Pemetrexed, a multitarget antifolate used to treat malignant mesothelioma and non-small cell lung cancer (NSCLC), has been shown to stimulate autophagy. In this study, we determined whether autophagy could be induced by pemetrexed and simvastatin cotreatment in malignant mesothelioma and NSCLC cells. Furthermore, we determined whether inhibition of autophagy drives apoptosis in malignant mesothelioma and NSCLC cells. Malignant mesothelioma MSTO-211H and A549 NSCLC cells were treated with pemetrexed and simvastatin alone and in combination to evaluate their effect on autophagy and apoptosis. Cotreatment with pemetrexed and simvastatin induced greater caspase-dependent apoptosis and autophagy than either drug alone in malignant mesothelioma and NSCLC cells. 3-Methyladenine (3-MA), ATG5 siRNA, bafilomycin A, and E64D/pepstatin A enhanced the apoptotic potential of pemetrexed and simvastatin, whereas rapamycin and LY294002 attenuated their induction of caspase-dependent apoptosis. Our data indicate that pemetrexed and simvastatin cotreatment augmented apoptosis and autophagy in malignant mesothelioma and NSCLC cells. Inhibition of pemetrexed and simvastatin-induced autophagy was shown to enhance apoptosis, suggesting that this could be a novel therapeutic strategy against malignant mesothelioma and NSCLC.

  14. Salivary gland-type tumors of the breast: a spectrum of benign and malignant tumors including "triple negative carcinomas" of low malignant potential.

    PubMed

    Foschini, Maria P; Krausz, Thomas

    2010-02-01

    Salivary gland-type neoplasms of the breast are uncommon and comprise numerous entities analogous to that more commonly seen in salivary glands. The clinicopathologic spectrum ranges from benign to malignant but there are important differences as compared with those of their salivary counterpart. In the breast, benign adenomyoepithelioma is recognized in addition to malignant one, whereas in the salivary gland a histologically similar tumor is designated as epithelial-myoepithelial carcinoma without a separate benign subgroup. Mammary adenoid cystic carcinoma is a low-grade neoplasm compared with its salivary equivalent. It is also important to appreciate that in contrast to "triple negative" conventional breast carcinomas with aggressive course, most salivary-type malignant breast neoplasms behave in a low-grade manner. Most of these tumors are capable of differentiating along both epithelial and myoepithelial lines, but the amount of each lineage-component varies from case to case, contributing to diagnostic difficulties. Well established examples of this group include pleomorphic adenoma, adenomyoepithelioma, and adenoid cystic carcinoma. Another family of salivary gland-type mammary epithelial neoplasms is devoid of myoepithelial cells. Key examples include mucoepidermoid carcinoma and acinic cell carcinoma. The number of cases of salivary gland-type mammary neoplasms in the published data is constantly increasing but some of the rarest subtypes like polymorphous low-grade adenocarcinoma and oncocytic carcinoma are "struggling" to become clinically relevant entities in line with those occurring more frequently in salivary glands.

  15. Preliminary analysis of salivary microbiome and their potential roles in oral lichen planus

    PubMed Central

    Wang, Kun; Lu, Wenxin; Tu, Qichao; Ge, Yichen; He, Jinzhi; Zhou, Yu; Gou, Yaping; Van Nostrand, Joy D; Qin, Yujia; Li, Jiyao; Zhou, Jizhong; Li, Yan; Xiao, Liying; Zhou, Xuedong

    2016-01-01

    Several studies have explored the origin and development mechanism of oral lichen planus (OLP) with limited attention to the role of bacteria in the progression of this common oral disease. Here we utilized MiSeq sequencing of 16S rRNA gene amplicons to identify complex oral microbiota associated with OLP from saliva samples of two subtypes (reticular and erosive) of OLP patients and healthy controls. Our analyses indicated that the overall structure of the salivary microbiome was not significantly affected by disease status. However, we did observe evident variations in abundance for several taxonomic groups in OLP. Porphyromonas and Solobacterium showed significantly higher relative abundances, whereas Haemophilus, Corynebacterium, Cellulosimicrobium and Campylobacter showed lower abundances in OLP patients, as compared with healthy controls. In addition, we explored specific microbial co-occurrence patterns in OLP, and revealed significantly fewer linkers of Streptococcus comprising species in erosive OLP. Furthermore, the disease severity and immune dysregulation were also genus-associated, including with Porphyromonas that correlated to disease scores and salivary levels of interleukin (IL)-17 and IL-23. Overall, this study provides a general description of oral microbiome in OLP, and it will be useful for further investigation of their potential roles in the initiation and immune modulation of OLP. PMID:26961389

  16. Recent trends in prevention of oral cancer.

    PubMed

    Mangalath, Ummar; Aslam, Sachin Aslam; Abdul Khadar, Abdul Hafiz Kooliyat; Francis, Pulikkan George; Mikacha, Muhamed Shaloob Karimbil; Kalathingal, Jubin Hassan

    2014-12-01

    Oral cancers often occurs out of long standing potentially malignant lesions and conditions so called premalignant lesions and conditions. Oral precancer is a intermediate state with increased cancer rate which can be recognized and treated obviously with much better prognosis than a full blown malignancy. Oral cancer risk can be lowered or even prevented by simply understanding basic oral hygiene, different bacteria found in the mouth, and how diet influences oral cancers. Currently, research is being done on the relationship between diet and oral cancer. Oral cancer is a very serious disease that can be prevented. Practicing good oral hygiene is key to help keep the oral cavity clean. Limiting the use of tobacco and alcohol products is also important because these are the causes of most oral cancers. Lastly, eating a well balanced diet that has protective affects can reduce the risk of oral cancer. This includes a diet high in fruits, vegetables, and fish and low in high fat and cholesterol meats, rice, and refined grains. PMID:25625069

  17. Recent trends in prevention of oral cancer

    PubMed Central

    Mangalath, Ummar; Aslam, Sachin Aslam; Abdul Khadar, Abdul Hafiz Kooliyat; Francis, Pulikkan George; Mikacha, Muhamed Shaloob Karimbil; Kalathingal, Jubin Hassan

    2014-01-01

    Oral cancers often occurs out of long standing potentially malignant lesions and conditions so called premalignant lesions and conditions. Oral precancer is a intermediate state with increased cancer rate which can be recognized and treated obviously with much better prognosis than a full blown malignancy. Oral cancer risk can be lowered or even prevented by simply understanding basic oral hygiene, different bacteria found in the mouth, and how diet influences oral cancers. Currently, research is being done on the relationship between diet and oral cancer. Oral cancer is a very serious disease that can be prevented. Practicing good oral hygiene is key to help keep the oral cavity clean. Limiting the use of tobacco and alcohol products is also important because these are the causes of most oral cancers. Lastly, eating a well balanced diet that has protective affects can reduce the risk of oral cancer. This includes a diet high in fruits, vegetables, and fish and low in high fat and cholesterol meats, rice, and refined grains. PMID:25625069

  18. Malignant potential of cells isolated from lymph node or brain metastases of melanoma patients and implications for prognosis.

    PubMed

    Zhang, R D; Price, J E; Schackert, G; Itoh, K; Fidler, I J

    1991-04-15

    We studied the correlation between the formation of brain metastasis and the malignant growth potential of seven human melanoma cell lines, isolated from lymph node metastases (A375-SM, TXM-1, DM-4) or from brain metastases (TXM-13, TXM-18, TXM-34, TXM-40), and the potential of three variants of the mouse K-1735 melanoma. Growth rates in different concentrations of fetal bovine serum and colony-forming efficiency in semisolid agarose were measured, and the tumorigenicity and metastatic ability were determined in nude mice (for the human melanoma cell lines) or in C3H/HeN mice (for the K-1735 variants). The ability to form brain metastasis was tested by injection of cells into the carotid artery. A high colony-forming efficiency in agarose, especially at concentrations of agarose greater than 0.6%, corresponded with high tumor take rates, rapid tumor growth rates, and metastatic colonization of the lungs of the recipient mice. For the human melanomas, the lymph node metastasis-derived cells were more tumorigenic and metastatic than the brain metastasis-derived cells. In the K-1735 mouse melanoma, the tumorigenic and metastatic behavior of the cells after i.v. and s.c. injection corresponded with growth in agarose cultures. However, for growth in the brain after intracarotid injection, the different melanoma cell lines showed similar frequencies of tumor take, regardless of tumorigenicity in other sites of the recipient mice, although mice given injections of brain metastasis-derived cells survived longer than mice given injections of lymph node metastasis (human melanoma) or lung metastasis (K-1735 M-2)-derived cell lines. The results from the human and mouse melanoma cell lines show that the brain metastasis-derived cell lines were not more malignant than the lymph node or lung metastasis-derived cells. These data imply that the production of brain metastasis is not always the final stage of a metastatic cascade. PMID:1826230

  19. Down-regulation of malignant potential by alpha linolenic acid in human and mouse colon cancer cells.

    PubMed

    Chamberland, John P; Moon, Hyun-Seuk

    2015-03-01

    Omega-3 fatty acids (also called ω-3 fatty acis or n-3 fatty acid) are polyunsaturated fatty acids (PUFAs) with a double bond (C=C) at the third carbon atom from the end of the carbon chain. Numerous test tube and animal studies have shown that omega-3 fatty acids may prevent or inhibit the growth of cancers, suggesting that omega-3 fatty acids are important in cancer physiology. Alpha-linolenic acid (ALA) is one of an essential omega-3 fatty acid and organic compound found in seeds (chia and flaxseed), nuts (notably walnuts), and many common vegetable oils. ALA has also been shown to down-regulate cell proliferation of prostate, breast, and bladder cancer cells. However, direct evidence that ALA suppresses to the development of colon cancer has not been studied. Also, no previous studies have evaluated whether ALA may regulate malignant potential (adhesion, invasion and colony formation) in colon cancer cells. In order to address the questions above, we conducted in vitro studies and evaluated whether ALA may down-regulate malignant potential in human (HT29 and HCT116) and mouse (MCA38) colon cancer cell lines. We observed that treatment with 1-5 mM of ALA inhibits cell proliferation, adhesion and invasion in both human and mouse colon cancer cell lines. Interestingly, we observed that ALA did not decrease total colony numbers when compared to control. By contrast, we found that size of colony was significantly changed by ALA treatment when compared to control in all colon cancer cell lines. We suggest that our data enhance our current knowledge of ALA's mechanism and provide crucial information to further the development of new therapies for the management or chemoprevention of colon cancer.

  20. Synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential: A clinico-pathologic and molecular study.

    PubMed

    Raspollini, Maria Rosaria; Castiglione, Francesca; Cheng, Liang; Montironi, Rodolfo; Lopez-Beltran, Antonio

    2016-05-01

    We report a rare case of synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential in the same kidney. The tumors were seen incidentally in a 45-year-old man. Pathologic study revealed that the former tumor was nucleolar grade 2, and the multilocular cystic renal cell neoplasia of low malignant potential was nucleolar grade 1. At immunohistochemistry, the clear cells in both tumors were positive for CD10 and CA IX. Interestingly, these uncommon synchronous tumors showed a different KRAS/NRAS mutation analysis that was characterized by KRAS mutation at codon p.G12C in the clear cell renal cell carcinoma, while this mutation was not present in the case of multilocular cystic renal cell neoplasia of low malignant potential. NRAS mutation was not seen in any of the tumors. PMID:26874573

  1. Complete Genome Sequence of Lactobacillus oris J-1, a Potential Probiotic Isolated from the Human Oral Microbiome

    PubMed Central

    2016-01-01

    Lactobacilli can exert health-promoting effects in the human oral microbiome through many mechanisms, including pathogen inhibition, maintenance of microbial balance, immunomodulation, and enhancement of the epithelial barrier function. Here, we present the complete genome sequence of a potential probiotic, Lactobacillus oris J-1, that was isolated from the oral cavity of a health child. PMID:27634996

  2. Complete Genome Sequence of Lactobacillus oris J-1, a Potential Probiotic Isolated from the Human Oral Microbiome.

    PubMed

    Jia, Fang

    2016-01-01

    Lactobacilli can exert health-promoting effects in the human oral microbiome through many mechanisms, including pathogen inhibition, maintenance of microbial balance, immunomodulation, and enhancement of the epithelial barrier function. Here, we present the complete genome sequence of a potential probiotic, Lactobacillus oris J-1, that was isolated from the oral cavity of a health child. PMID:27634996

  3. Complete Genome Sequence of Lactobacillus oris J-1, a Potential Probiotic Isolated from the Human Oral Microbiome.

    PubMed

    Jia, Fang

    2016-01-01

    Lactobacilli can exert health-promoting effects in the human oral microbiome through many mechanisms, including pathogen inhibition, maintenance of microbial balance, immunomodulation, and enhancement of the epithelial barrier function. Here, we present the complete genome sequence of a potential probiotic, Lactobacillus oris J-1, that was isolated from the oral cavity of a health child.

  4. [Oral medicine 7: white lesions of the oral mucosa].

    PubMed

    de Visscher, J G A M; van der Meij, E H; Schepman, K P

    2013-06-01

    White lesions of the oral mucosa may be due to highly diverse disorders. Most of these disorders are benign but some may be a malignant or premalignant condition. The disease is often confined to the oral mucosa. There are also disorders which are accompanied by skin disorders or systemic diseases. Many white oral mucosa disorders have such characteristic clinical aspects that a diagnosis can be made on clinical grounds only. When the clinical diagnosis is not clear, histopathological examination is carried out. Treatment depends on the histological diagnosis. In some cases, treatment is not necessary while in other cases, treatment is not possible since an effective treatment is not available. Potentially malignant disorders are treated.

  5. Inhaled vs. oral alprazolam: subjective, behavioral and cognitive effects, and modestly increased abuse potential

    PubMed Central

    Reissig, Chad J.; Harrison, Joseph A.; Carter, Lawrence P.; Griffiths, Roland R.

    2014-01-01

    Rationale Infrahuman and human studies suggest that a determinant of the abuse potential of a drug is rate of onset of subjective effects. Objectives This study sought to determine if the rate of onset of subjective effects and abuse potential of alprazolam would be increased when administered via inhalation vs. the oral route. Methods Placebo, inhaled alprazolam (0.5, 1, 2 mg), and oral alprazolam (1, 2, 4 mg) were administered under double-blind, double-dummy conditions using a cross-over design in 14 healthy participants with histories of drug abuse. Participant and observer ratings, and behavioral and cognitive performance measures were assessed repeatedly during 9 hour sessions. Results Both routes of administration produced orderly dose and time-related effects, with higher doses producing greater and longer lasting effects. Onset of subjective effects following inhaled alprazolam was very rapid (e.g., 2 vs. 49 minutes after 2 mg inhaled vs. oral). On measures of abuse potential (e.g., liking and good effects), inhaled alprazolam was more potent, as evidenced by a leftward shift in the dose response curve. Despite the potency difference, at the highest doses, peak ratings of subjective effects related to abuse potential (e.g., “drug liking”) were similar across the two routes. On other measures (e.g., sedation and performance) the routes were equipotent. Conclusions The inhaled route of administration modestly increased the abuse potential of alprazolam despite significantly increasing its rate of onset. If marketed, the reduced availability and increased cost of inhaled alprazolam may render the societal risk of increased abuse to be low. PMID:25199955

  6. Exosomes as potent regulators of HCC malignancy and potential bio-tools in clinical application

    PubMed Central

    Qu, Zhen; Jiang, Chunping; Wu, Junhua; Ding, Yitao

    2015-01-01

    Exosomes are small membranous vesicles about 30~100 nm in diameter and formed from inward budding of the limiting membrane of multi-vesicular bodies (MVB). Exosomes are secreted by most cell types (including hepatocellular carcinoma cells) into the extracellular environment and can be isolated from various body fluids. Exosomes have broad biological function through delivering contained molecules to the target cells. Although limited studies on hepatocellular carcinoma (HCC) exosomes, increasing observations suggest that exosomes are important in HCC metastatic and prognosis, and exosomes are potential new molecular biomarkers for diagnosis and prognosis of HCC. In this review, we briefly summarize the latest findings on HCC exosomes, and their potential functions for novel diagnostic and therapeutic approaches of HCC. PMID:26770301

  7. NMS-P937, an orally available, specific small-molecule polo-like kinase 1 inhibitor with antitumor activity in solid and hematologic malignancies.

    PubMed

    Valsasina, Barbara; Beria, Italo; Alli, Cristina; Alzani, Rachele; Avanzi, Nilla; Ballinari, Dario; Cappella, Paolo; Caruso, Michele; Casolaro, Alessia; Ciavolella, Antonella; Cucchi, Ulisse; De Ponti, Anna; Felder, Eduard; Fiorentini, Francesco; Galvani, Arturo; Gianellini, Laura M; Giorgini, Maria L; Isacchi, Antonella; Lansen, Jaqueline; Pesenti, Enrico; Rizzi, Simona; Rocchetti, Maurizio; Sola, Francesco; Moll, Jürgen

    2012-04-01

    Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase considered to be the master player of cell-cycle regulation during mitosis. It is indeed involved in centrosome maturation, bipolar spindle formation, chromosome separation, and cytokinesis. PLK1 is overexpressed in a variety of human tumors and its overexpression often correlates with poor prognosis. Although five different PLKs are described in humans, depletion or inhibition of kinase activity of PLK1 is sufficient to induce cell-cycle arrest and apoptosis in cancer cell lines and in xenograft tumor models. NMS-P937 is a novel, orally available PLK1-specific inhibitor. The compound shows high potency in proliferation assays having low nanomolar activity on a large number of cell lines, both from solid and hematologic tumors. NMS-P937 potently causes a mitotic cell-cycle arrest followed by apoptosis in cancer cell lines and inhibits xenograft tumor growth with clear PLK1-related mechanism of action at well-tolerated doses in mice after oral administration. In addition, NMS-P937 shows potential for combination in clinical settings with approved cytotoxic drugs, causing tumor regression in HT29 human colon adenocarcinoma xenografts upon combination with irinotecan and prolonged survival of animals in a disseminated model of acute myelogenous leukemia in combination with cytarabine. NMS-P937, with its favorable pharmacologic parameters, good oral bioavailability in rodent and nonrodent species, and proven antitumor activity in different preclinical models using a variety of dosing regimens, potentially provides a high degree of flexibility in dosing schedules and warrants investigation in clinical settings.

  8. Epidermal growth factor (EGF) as a potential targeting agent for delivery of boron to malignant gliomas

    SciTech Connect

    Capala, J.; Barth, R.F.; Adams, D.M.; Bailey, M.Q.; Soloway, A.H.; Carlsson, J.

    1994-12-31

    The majority of high grade gliomas express an amplified epidermal growth factor receptor (EGFR) gene, and this often is associated with an increase in cell surface receptor expression. The rapid internalization and degradation of EGF-EGFR complexes, as well as their high affinity make EGF a potential targeting agent for delivery of {sup 10}B to tumor cells with an amplified number of EGFR. Human glioma cells can expresses as many as 10{sup 5} {minus}10{sup 6} EGF receptors per cell, and if these could be saturated with boronated EGF, then > 10{sup 8} boron atoms would be delivered per cell. Since EGF has a comparatively low molecular weight ({approximately} 6 kD), this has allowed us to construct relatively small bioconjugates containing {approximately} 900 boron atoms per EGF molecule{sup 3}, which also had high affinity for EGFR on tumor cells. In the present study, the feasibility of using EGF receptors as a potential target for therapy of gliomas was investigated by in vivo scintigraphic studies using {sup 131}I{minus} or {sup 99m}{Tc}-labeled EGF in a rat brain tumor model. Our results indicate that intratumorally delivered boron- EGF conjugates might be useful for targeting EGFR on glioma cells if the boron containing moiety of the conjugates persisted intracellularly. Further studies are required, however, to determine if this approach can be used for BNCT of the rat glioma.

  9. Molecular markers and imaging tools to identify malignant potential in Barrett's esophagus

    PubMed Central

    Bennett, Michael; Mashimo, Hiroshi

    2014-01-01

    Due to its rapidly rising incidence and high mortality, esophageal adenocarcinoma is a major public health concern, particularly in Western countries. The steps involved in the progression from its predisposing condition, gastroesophageal reflux disease, to its premalignant disorder, Barrett’s esophagus, and to cancer, are incompletely understood. Current screening and surveillance methods are limited by the lack of population-wide utility, incomplete sampling of standard biopsies, and subjectivity of evaluation. Advances in endoscopic ablation have raised the hope of effective therapy for eradication of high-risk Barrett’s lesions, but improvements are needed in determining when to apply this treatment and how to follow patients clinically. Researchers have evaluated numerous potential molecular biomarkers with the goal of detecting dysplasia, with varying degrees of success. The combination of biomarker panels with epidemiologic risk factors to yield clinical risk scoring systems is promising. New approaches to sample tissue may also be combined with these biomarkers for less invasive screening and surveillance. The development of novel endoscopic imaging tools in recent years has the potential to markedly improve detection of small foci of dysplasia in vivo. Current and future efforts will aim to determine the combination of markers and imaging modalities that will most effectively improve the rate of early detection of high-risk lesions in Barrett’s esophagus. PMID:25400987

  10. [Oral medicine 8. Leukoplakia of the oral mucosa].

    PubMed

    Schepman, K P; van der Meij, E H; de Visscher, J G A M

    2013-01-01

    Leukoplakia of the oral mucosa is a potentially malignant disorder, which means that there is an elevated risk oftransformation into a squamous cell carcinoma. The term oral leukoplakia is a clinical diagnosis for a predominantly white lesion which is not immediately recognizable as another well definable lesion which is white in appearance. Oral leukoplakia is generally an asymptomatic disorder of the mucosa with a prevalence of less than 2 per cent in the adult population. Tobacco usage is considered to be the most important etiological factor. Malignant transformation into a squamous cell carcinoma occurs in about I per cent per year. A patient with oral leukoplakia is generally referred to an oral and maxillofacial surgeon, who takes a biopsy for a definitive histopathological diagnosis. The outcome of the histopathological study, which may vary from hyperkeratosis to invasive squamous cell carcinoma, will determine the treatment. It is preferable that every leukoplakia is removed to reduce the risk of malignant transformation. Long term follow-up is indicated. Follow-up may in some cases be performed by the general dental practitioner.

  11. The anti-tubercular drug delamanid as a potential oral treatment for visceral leishmaniasis

    PubMed Central

    Patterson, Stephen; Wyllie, Susan; Norval, Suzanne; Stojanovski, Laste; Simeons, Frederick RC; Auer, Jennifer L; Osuna-Cabello, Maria; Read, Kevin D; Fairlamb, Alan H

    2016-01-01

    There is an urgent requirement for safe, oral and cost-effective drugs for the treatment of visceral leishmaniasis (VL). We report that delamanid (OPC-67683), an approved drug for multi-drug resistant tuberculosis, is a potent inhibitor of Leishmania donovani both in vitro and in vivo. Twice-daily oral dosing of delamanid at 30 mg kg-1 for 5 days resulted in sterile cures in a mouse model of VL. Treatment with lower doses revealed a U-shaped (hormetic) dose-response curve with greater parasite suppression at 1 mg kg-1 than at 3 mg kg-1 (5 or 10 day dosing). Dosing delamanid for 10 days confirmed the hormetic dose-response and improved the efficacy at all doses investigated. Mechanistic studies reveal that delamanid is rapidly metabolised by parasites via an enzyme, distinct from the nitroreductase that activates fexinidazole. Delamanid has the potential to be repurposed as a much-needed oral therapy for VL. DOI: http://dx.doi.org/10.7554/eLife.09744.001 PMID:27215734

  12. Functionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery

    PubMed Central

    Coyuco, Jurja C; Liu, Yuanjie; Tan, Bee-Jen; Chiu, Gigi NC

    2011-01-01

    Although carbon nanomaterials (CNMs) have been increasingly studied for their biomedical applications, there is limited research on these novel materials for oral drug delivery. As such, this study aimed to explore the potential of CNMs in oral drug delivery, and the objectives were to evaluate CNM cytotoxicity and their abilities to modulate paracellular transport and the P-glycoprotein (P-gp) efflux pump. Three types of functionalized CNMs were studied, including polyhydroxy small-gap fullerenes (OH-fullerenes), carboxylic acid functionalized single-walled carbon nanotubes (f SWCNT-COOH) and poly(ethylene glycol) functionalized single-walled carbon nanotubes (f SWCNT-PEG), using the well-established Caco-2 cell monolayer to represent the intestinal epithelium. All three CNMs had minimum cytotoxicity on Caco-2 cells, as demonstrated through lactose dehydrogenase release and 3-(4,5-dimethyliazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Of the three CNMs, f SWCNT-COOH significantly reduced transepithelial electrical resistance and enhanced transport of Lucifer Yellow across the Caco-2 monolayer. Confocal fluorescence microscopy showed that f SWCNT-COOH treated cells had the highest perturbation in the distribution of ZO-1, a protein marker of tight junction, suggesting that f SWCNT-COOH could enhance paracellular permeability via disruption of tight junctions. This modulating effect of f SWCNT-COOH can be reversed over time. Furthermore, cellular accumulation of the P-gp substrate, rhodamine-123, was significantly increased in cells treated with f SWCNT-COOH, suggestive of P-gp inhibition. Of note, f SWCNT-PEG could increase rhodamine-123 accumulation without modifying the tight junction. Collectively, these results suggest that the functionalized CNMs could be useful as modulators for oral drug delivery, and the differential effects on the intestinal epithelium imparted by different types of CNMs would create unique opportunities for drug-specific oral

  13. Human BK Polyomavirus—The Potential for Head and Neck Malignancy and Disease

    PubMed Central

    Burger-Calderon, Raquel; Webster-Cyriaque, Jennifer

    2015-01-01

    Members of the human Polyomaviridae family are ubiquitous and pathogenic among immune-compromised individuals. While only Merkel cell polyomavirus (MCPyV) has conclusively been linked to human cancer, all members of the polyomavirus (PyV) family encode the oncoprotein T antigen and may be potentially carcinogenic. Studies focusing on PyV pathogenesis in humans have become more abundant as the number of PyV family members and the list of associated diseases has expanded. BK polyomavirus (BKPyV) in particular has emerged as a new opportunistic pathogen among HIV positive individuals, carrying harmful implications. Increasing evidence links BKPyV to HIV-associated salivary gland disease (HIVSGD). HIVSGD is associated with elevated risk of lymphoma formation and its prevalence has increased among HIV/AIDS patients. Determining the relationship between BKPyV, disease and tumorigenesis among immunosuppressed individuals is necessary and will allow for expanding effective anti-viral treatment and prevention options in the future. PMID:26184314

  14. Human BK Polyomavirus-The Potential for Head and Neck Malignancy and Disease.

    PubMed

    Burger-Calderon, Raquel; Webster-Cyriaque, Jennifer

    2015-07-08

    Members of the human Polyomaviridae family are ubiquitous and pathogenic among immune-compromised individuals. While only Merkel cell polyomavirus (MCPyV) has conclusively been linked to human cancer, all members of the polyomavirus (PyV) family encode the oncoprotein T antigen and may be potentially carcinogenic. Studies focusing on PyV pathogenesis in humans have become more abundant as the number of PyV family members and the list of associated diseases has expanded. BK polyomavirus (BKPyV) in particular has emerged as a new opportunistic pathogen among HIV positive individuals, carrying harmful implications. Increasing evidence links BKPyV to HIV-associated salivary gland disease (HIVSGD). HIVSGD is associated with elevated risk of lymphoma formation and its prevalence has increased among HIV/AIDS patients. Determining the relationship between BKPyV, disease and tumorigenesis among immunosuppressed individuals is necessary and will allow for expanding effective anti-viral treatment and prevention options in the future.

  15. Dissecting the Origin of Breast Cancer Subtype Stem Cell and the Potential Mechanism of Malignant Transformation

    PubMed Central

    Liu, Dianming; Wang, Shuyuan; Yu, Xuexin; Dai, Enyu; Wang, Jing; Wang, Lihong; Jiang, Wei

    2016-01-01

    Background Breast cancer is the most common incident form of cancer in women including different subtypes. Cancer stem cells (CSCs) have been confirmed to exist in breast cancer. But the research on the origin of breast cancer subtype stem cells (BCSSCs) is still inadequate. Methods We identified the putative origin cells of BCSSCs through comparing gene signatures between BCSSCs and normal mammary cells from multiple perspectives: common signature, expression consistency, functional similarity and shortest path length. First, the potential origin cells were ranked according to these measures separately. Then Q statistic was employed to combine all rank lists into a unique list for each subtype, to prioritize the origin cells for each BCSSC. Next, we identified origin-related gene modules through integrating functional interaction network with differentially expressed genes. Finally, transcription factors of significant gene modules were predicted by MatchTM. Results The results showed that Luminal A CSC was most relevant to luminal progenitor cell or mature luminal cell; luminal B and HER2 CSC were most relevant to bipotent-enriched progenitor cell; basal-like CSC was most relevant to bipotent-enriched progenitor cell or mature luminal cell. Network modules analysis revealed genes related to mitochondrial respiratory chain (MRC) were significantly dysregulated during the origin of luminal B CSC. In addition, SOX10 emerged as a key regulator of MRC. Conclusions Our study supports substantive evidence for the possible origin of four kinds of BCSSCs. Dysfunction of MRC may contribute to the origin of luminal B CSC. These findings may have important implications to treat and prevent breast cancer. PMID:27768723

  16. Malignant hyperthermia.

    PubMed

    Cantin, R Y; Poole, A; Ryan, J F

    1986-10-01

    The increasing use of intravenous and inhalation sedation in the dental office has the potential of increasing the incidence of malignant hyperthermia (MH) in susceptible subjects. The object of this article is to present two cases of MH and to discuss its pathophysiology, its clinical picture, and its management in the light of the current literature. Stringent screening procedures should be adopted and maintained in order to channel suspected cases to appropriate centers for expert consultation and management. It is further advocated that a program of education for patients and their families be instituted, as it is an essential prerequisite of effective prophylaxis. PMID:2946013

  17. Role of micronucleus in oral exfoliative cytology

    PubMed Central

    Shashikala, R.; Indira, A. P.; Manjunath, G. S.; rao, K. Arathi; Akshatha, B. K.

    2015-01-01

    In the last few years, the interest for oral cytology as a diagnostic and prognostic methodology, for monitoring patients in oral potentially malignant disorders and oral cancer has re-emerged substantially. In 1983, buccal mucosal micronuclei assay was first proposed to evaluate genetic instability. There are biomarkers that predict if a potentially malignant disorder is likely to develop into an aggressive tumor. These genotoxic and carcinogenic chemicals have been reported to be potent clastogenic and mutagenic agents which are thought to be responsible for the induction of chromatid/chromosomal aberrations resulting in the production of micronuclei. Various studies have concluded that the gradual increase in micronucleus (MN) counts from normal oral mucosa to potentially malignant disorders to oral carcinoma suggested a link of this biomarker with neoplastic progression. MN scoring can be used as a biomarker to identify different preneoplastic conditions much earlier than the manifestations of clinical features and might specifically be exploited in the screening of high-risk population for a specific cancer. Hence, it can be used as a screening prognostic and educational tool in community centers of oral cancer. PMID:26538888

  18. Bruton’s tyrosine kinase inhibitors and their clinical potential in the treatment of B-cell malignancies: focus on ibrutinib

    PubMed Central

    Aalipour, Amin

    2014-01-01

    Aberrant signaling of the B-cell receptor pathway has been linked to the development and maintenance of B-cell malignancies. Bruton’s tyrosine kinase (BTK), a protein early in this pathway, has emerged as a new therapeutic target in a variety of such malignancies. Ibrutinib, the most clinically advanced small molecule inhibitor of BTK, has demonstrated impressive tolerability and activity in a range of B-cell lymphomas which led to its recent approval for relapsed mantle cell lymphoma and chronic lymphocytic leukemia. This review focuses on the preclinical and clinical development of ibrutinib and discusses its therapeutic potential. PMID:25360238

  19. Evaluation of oral bioavailability and anticancer potential of raloxifene solid lipid nanoparticles.

    PubMed

    Battani, Somashekhar; Pawar, Harish; Suresh, Sarasija

    2014-08-01

    The objective of the present investigation was formulation of raloxifene loaded solid lipid nanoparticles (R-SLN) for oral administration and evaluation of its anticancer potential in 7,12- dimethylbenzanthracene (DMBA)-induced breast cancer in Sprague-Dawley rats. Optimized R-SLN formulation prepared by modified micro-emulsion method resulted in R-SLN of 288.0±28.5 nm size and 95.56% entrapment efficiency. R-SLN exhibited in vitro prolonged release of raloxifene for 72 h in phosphate buffered saline. R-SLN was stable in simulated gastro-intestinal (GIT) fluids consisting of pH 1.2, pH 7.4, simulated gastric fluid and simulated intestinal fluid. A two-fold increase was observed in raloxifene oral bioavailability from R-SLN. R-SLN exhibited enhanced efficacy and chemopreventive activity over pure raloxifene as indicated by evaluation of tumor burden (P < 0.001) and tumor incidence (P < 0.001). The results indicate the potential of raloxifene solid lipid nanoparticles in optimizing chemoprevention of breast cancer by R-SLN. PMID:25935981

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

    PubMed Central

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

    2011-01-01

    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. PMID:22013381

  1. Plant and fungal food components with potential activity on the development of microbial oral diseases.

    PubMed

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

    2011-01-01

    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. PMID:22013381

  2. Morphological characteristics of potentially malignant pulmonary nodules in high-risk male smokers detected in lung cancer screening trial in Cracow, Poland.

    PubMed

    Kiszka, K; Rudnicka-Sosin, L; Tomaszewska, R; Urbańczyk-Zawadzka, M; Krupiński, M; Pikul, P; Podsiadło, K; Pasowicz, M; Vliegenthart, R; Oudkerk, M; Miszalski-Jamka, T

    2013-06-01

    The purpose of this paper was to present morphological characteristics of potentially malignant nodules revealed in a group of male smokers aged 50-74 with a very high risk for developing lung cancer estimated in the study for lung cancer screening in Cracow (Poland). Nine hundred male smokers aged 50 to 74 years were invited to the study and were asked in questionnaires about e.g. smoking exposure history. Exclusion criteria included e.g. positive cancer history and chest computed tomography (CT) examination in the previous year. Based on CT results and characteristics of pulmonary nodules subjects were classified to group A (low risk), group B (indeterminate) and group C (high-risk individuals - required work-up). Final diagnosis was based on pathological results of postoperative material. Thirty-nine males of mean age 63.4 (standard deviation (SD): 6.69 years) revealed 41 potentially malignant pulmonary nodules in baseline screening. In 14 subjects 16 type C pulmonary nodules were histologically proved. Nine nodules were found to be benign lesions, while 7 nodules revealed malignant lung cancer: 5 cases of adenocarcinoma and 2 cases of adenosquamous carcinoma. We determined morphological characteristics of potentially malignant pulmonary nodules in 39 high-risk male smokers and proved lung cancer in 7 subjects.

  3. Potential Compounds for Oral Cancer Treatment: Resveratrol, Nimbolide, Lovastatin, Bortezomib, Vorinostat, Berberine, Pterostilbene, Deguelin, Andrographolide, and Colchicine

    PubMed Central

    Bundela, Saurabh; Sharma, Anjana; Bisen, Prakash S.

    2015-01-01

    Oral cancer is one of the main causes of cancer-related deaths in South-Asian countries. There are very limited treatment options available for oral cancer. Research endeavors focused on discovery and development of novel therapies for oral cancer, is necessary to control the ever rising oral cancer related mortalities. We mined the large pool of compounds from the publicly available compound databases, to identify potential therapeutic compounds for oral cancer. Over 84 million compounds were screened for the possible anti-cancer activity by custom build SVM classifier. The molecular targets of the predicted anti-cancer compounds were mined from reliable sources like experimental bioassays studies associated with the compound, and from protein-compound interaction databases. Therapeutic compounds from DrugBank, and a list of natural anti-cancer compounds derived from literature mining of published studies, were used for building partial least squares regression model. The regression model thus built, was used for the estimation of oral cancer specific weights based on the molecular targets. These weights were used to compute scores for screening the predicted anti-cancer compounds for their potential to treat oral cancer. The list of potential compounds was annotated with corresponding physicochemical properties, cancer specific bioactivity evidences, and literature evidences. In all, 288 compounds with the potential to treat oral cancer were identified in the current study. The majority of the compounds in this list are natural products, which are well-tolerated and have minimal side-effects compared to the synthetic counterparts. Some of the potential therapeutic compounds identified in the current study are resveratrol, nimbolide, lovastatin, bortezomib, vorinostat, berberine, pterostilbene, deguelin, andrographolide, and colchicine. PMID:26536350

  4. NRF2 Mutation Confers Malignant Potential and Resistance to Chemoradiation Therapy in Advanced Esophageal Squamous Cancer1

    PubMed Central

    Shibata, Tatsuhiro; Kokubu, Akiko; Saito, Shigeru; Narisawa-Saito, Mako; Sasaki, Hiroki; Aoyagi, Kazuhiko; Yoshimatsu, Yuki; Tachimori, Yuji; Kushima, Ryoji; Kiyono, Tohru; Yamamoto, Masayuki

    2011-01-01

    Esophageal squamous cancer (ESC) is one of the most aggressive tumors of the gastrointestinal tract. A combination of chemotherapy and radiation therapy (CRT) has improved the clinical outcome, but the molecular background determining the effectiveness of therapy remains unknown. NRF2 is a master transcriptional regulator of stress adaptation, and gain of-function mutation of NRF2 in cancer confers resistance to stressors including anticancer therapy. Direct resequencing analysis revealed that Nrf2 gain-of-function mutation occurred recurrently (18/82, 22%) in advanced ESC tumors and ESC cell lines (3/10). The presence of Nrf2 mutation was associated with tumor recurrence and poor prognosis. Short hairpin RNA-mediated down-regulation of NRF2 in ESC cells that harbor only mutated Nrf2 allele revealed that themutant NRF2 conferred increased cell proliferation, attachment-independent survival, and resistance to 5-fluorouracil and γ-irradiation. Based on the Nrf2 mutation status, gene expression signatures associated with NRF2 mutation were extracted from ESC cell lines, and their potential utility for monitoring and prognosis was examined in a cohort of 33 pre-CRT cases of ESC. The molecular signatures of NRF2 mutation were significantly predictive and prognostic for CRT response. In conclusion, recurrent NRF2 mutation confers malignant potential and resistance to therapy in advanced ESC, resulting in a poorer outcome. Molecular signatures of NRF2 mutation can be applied as predictive markers of response to CRT, and efficient inhibition of aberrant NRF2 activation could be a promising approach in combination with CRT. PMID:21969819

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

    PubMed

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

    2012-01-01

    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.

  6. Investigating potential exogenous tumor initiating and promoting factors for Cutaneous T-Cell Lymphomas (CTCL), a rare skin malignancy.

    PubMed

    Litvinov, Ivan V; Shtreis, Anna; Kobayashi, Kenneth; Glassman, Steven; Tsang, Matthew; Woetmann, Anders; Sasseville, Denis; Ødum, Niels; Duvic, Madeleine

    2016-07-01

    Most skin malignancies are caused by external and often preventable environmental agents. Multiple reports demonstrated that cutaneous T-cell lymphomas (CTCL) can occur in married couples and cluster in families. Furthermore, recent studies document geographic clustering of this malignancy in Texas as well as in other areas of the United States. Multiple infectious, occupational, and medication causes have been proposed as triggers or promoters of this malignancy including hydrochlorothiazide diuretics, Staphylococcus aureus, dermatophytes, Mycobacterium leprae, Chlamydia pneumoniae, human T-Cell lymphotropic virus type 1 (HTLV1), Epstein-Barr virus (EBV), and herpes simplex virus (HSV). In this report, we review recent evidence evaluating the involvement of these agents in cancer initiation/progression. Most importantly, recent molecular experimental evidence documented for the first time that S. aureus can activate oncogenic STAT3 signaling in malignant T cells. Specifically, S. aureus Enterotoxin type A (SEA) was recently shown to trigger non-malignant infiltrating T cells to release IL-2 and other cytokines. These signals upon binging to their cognate receptors on malignant T cells are then able to activate STAT3 and STAT5 oncogenic signaling and promote cancer progression and IL-17 secretion. In light of these findings, it might be important for patients with exacerbation of their CTCL symptoms to maintain high index of suspicion and treat these individuals for S. aureus colonization and/or sepsis with topical and systemic antibiotics. PMID:27622024

  7. Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential

    SciTech Connect

    Song, Kai; Song, Yong; Zhao, Xiao-Ping; Shen, Hui; Wang, Meng; Yan, Ting-lin; Liu, Ke; Shang, Zheng-jun

    2014-10-15

    Most previous studies have linked cancer–macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression. - Highlights: • The fusion events between oral cancer and endothelial cells undergo nuclear fusion. • The resulting hybrid cells acquire a new property of drug resistance. • The resulting hybrid cells express the markers of both parental cells (i.e. vimentin and cytokeratin 18). • The hybrid cells contribute to tumor repopulation in vivo.

  8. In vivo confocal microscopy for the oral cavity: Current state of the field and future potential.

    PubMed

    Maher, N G; Collgros, H; Uribe, P; Ch'ng, S; Rajadhyaksha, M; Guitera, P

    2016-03-01

    Confocal microscopy (CM) has been shown to correlate with oral mucosal histopathology in vivo. The purposes of this review are to summarize what we know so far about in vivo CM applications for oral mucosal pathologies, to highlight some current developments with CM devices relevant for oral applications, and to formulate where in vivo CM could hold further application for oral mucosal diagnosis and management. Ovid Medline® and/or Google® searches were performed using the terms 'microscopy, confocal', 'mouth neoplasms', 'mouth mucosa', 'leukoplakia, oral', 'oral lichen planus', 'gingiva', 'cheilitis', 'taste', 'inflammatory oral confocal', 'mucosal confocal' and 'confocal squamous cell oral'. In summary, inclusion criteria were in vivo use of any type of CM for the human oral mucosa and studies on normal or pathological oral mucosa. Experimental studies attempting to identify proteins of interest and microorganisms were excluded. In total 25 relevant articles were found, covering 8 main topics, including normal oral mucosal features (n=15), oral dysplasia or neoplasia (n=7), inflamed oral mucosa (n=3), taste impairment (n=3), oral autoimmune conditions (n=2), pigmented oral pathology/melanoma (n=1), delayed type hypersensitivity (n=1), and cheilitis glandularis (n=1). The evidence for using in vivo CM in these conditions is poor, as it is limited to mainly small descriptive studies. Current device developments for oral CM include improved probe design. The authors propose that future applications for in vivo oral CM may include burning mouth syndrome, intra-operative mapping for cancer surgery, and monitoring and targeted biopsies within field cancerization. PMID:26786962

  9. Oral medicine and the ageing population.

    PubMed

    Yap, T; McCullough, M

    2015-03-01

    The oral cavity is subject to age related processes such as cellular ageing and immunosenescence. The ageing population bears an increased burden of intraoral pathology. In oral medicine, the majority of presenting patients are in their fifth to seventh decade of life. In this review, we discuss the ageing population's susceptibility to mucosal disorders and the increased prevalence of potentially malignant disorders and oral squamous cell carcinoma, as well as dermatoses including oral lichen planus and immunobullous conditions. We also address the ageing population's susceptibility to oral discomfort and explore salivary secretion, ulceration and the symptoms of oral burning. Finally, we will describe orofacial pain conditions which are more likely encountered in an older population. This update highlights clinical presentations which are more likely to be encountered in the ageing population in a general practice setting and the importance of screening both new and long-term patients.

  10. Oral medicine and the ageing population.

    PubMed

    Yap, T; McCullough, M

    2015-03-01

    The oral cavity is subject to age related processes such as cellular ageing and immunosenescence. The ageing population bears an increased burden of intraoral pathology. In oral medicine, the majority of presenting patients are in their fifth to seventh decade of life. In this review, we discuss the ageing population's susceptibility to mucosal disorders and the increased prevalence of potentially malignant disorders and oral squamous cell carcinoma, as well as dermatoses including oral lichen planus and immunobullous conditions. We also address the ageing population's susceptibility to oral discomfort and explore salivary secretion, ulceration and the symptoms of oral burning. Finally, we will describe orofacial pain conditions which are more likely encountered in an older population. This update highlights clinical presentations which are more likely to be encountered in the ageing population in a general practice setting and the importance of screening both new and long-term patients. PMID:25762041

  11. Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential.

    PubMed

    Song, Kai; Song, Yong; Zhao, Xiao-Ping; Shen, Hui; Wang, Meng; Yan, Ting-Lin; Liu, Ke; Shang, Zheng-Jun

    2014-10-15

    Most previous studies have linked cancer-macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression.

  12. Use of everted intestinal rings for in vitro examination of oral absorption potential.

    PubMed

    Leppert, P S; Fix, J A

    1994-07-01

    The ability to predict in vivo oral absorption potential based on ex vivo screening in an everted intestinal ring model was examined. In vitro drug accumulation in cross sectional rings of everted rat jejunum was determined with 12 compounds whose in vivo absorptions (as distinct from bioavailabilities) are well characterized. The compounds examined ranged from well- to poorly-absorbed and included compounds absorbed by active and passive mechanisms. The effects of drug concentration, pH, cosolvents, and tissue origin site on drug accumulation were determined. Light microscopic observation indicated that the mucosal tissue remained intact up to 3 h after the intestine was excised. Accumulations of two nonabsorbable markers were also determined as measures of tissue integrity. A strong correlation (slope = 23 pmol/mg of tissue weight per percent oral absorption, r2 = 0.9430 by linear regression analysis) of in vitro uptake into everted rings from a 10 mM drug solution versus the known in vivo bioavailability for each compound was observed. These results indicated that under appropriate conditions, in vitro uptake of drug by the everted intestinal ring model closely paralleled known in vivo bioavailability and was relatively independent of pH, cosolvent, and tissue origin.

  13. The potential role of microbes in oncogenesis with particular emphasis on oral cancer

    PubMed Central

    Faden, Asmaa A.

    2016-01-01

    For over a century, non-virus microorganisms, notably bacteria have been implicated as causal agents of cancers, a relatively small number of researchers have provided evidence to support the so-called “cancer germ” hypothesis. With the exception of the link between Helicobacter pylori and stomach cancer, other supposed links have been ignored. A wide range of bacteria and other non-virus microbes, including fungi, have been implicated over the years in oncogenesis, as well as the ability to induce inflammation, which may cause cancer. It seems that there is no single “cancer germ,” as most bacteria can apparently induce cancer. Here, the role of bacteria and other non-virus microorganisms and oral cancers will be discussed. By ignoring bacteria as a causal agent of cancer, we set back our understanding of this crucially important disease and, as a result, have hindered the development of potential cures. PMID:27279505

  14. In vitro analysis of the cariogenic and erosive potential of paediatric antitussive liquid oral medications.

    PubMed

    Cavalcanti, Alessandro L; De Sousa, Rayanne I M; Clementino, Marayza A; Vieira, Fernando F; Cavalcanti, Christiane L; Xavier, Alidianne F C

    2012-04-01

    We evaluated in vitro the cariogenic and erosive potential of antitussive liquid oral medications for paediatric use. Fifteen paediatric liquid antitussives were sampled. The endogenous pH was evaluated by potentiometry, titratable acidity was measured according to the method adopted by the Association of Official Analytical Chemists, total soluble solids content (TSSC) readings were performed by Brix refractometry using the Abbé refractometer, and the total sugar content was determined according to the Fehling methodology. The experiments were performed in triplicate and the obtained data were entered in the Excel software, analyzed and presented by descriptive statistics (means and standard deviations). Endogenous pH values ranged from 2.49 ± 0.09 (Iodetox®) to 6.75 ± 0.005 (Carbocysteine®) and twelve medications showed pHs below the critical value of 5.5 for enamel demineralization. Iodetox® (0.021 ± 0.01) presented the lowest titratable acidity and Aerofrin® (1.171 ± 0.01) presented the highest titratable acidity. Celergin® presented the highest TSSC (62.26 ± 0.40) and Acetyleysteine® (100 mg granules bags) presented the lowest TSSC (3.25 ± 0.43). Only 5 medications contained sugar, with total sugar content ranging from 35.93% ± 6.65 (Iodetox®) to 59.60% DP ± 6.66 (Celergin®). The paediatric antitussive medications showed low endogenous pH, some of them even below the critical value for enamel dissolution (pH<5.5). These antitussives are potentially cariogenic and erosive to dental structures if used frequently because of the high titratable acidity and high sugar concentration, especially when adequate oral clearance is not performed after administration of each dose.

  15. Oral lichen planus.

    PubMed

    Olson, Meredith A; Rogers, Roy S; Bruce, Alison J

    2016-01-01

    Lichen planus is an inflammatory mucocutaneous disease that can affect the skin, hair, nails, and mucosal surfaces. Mucosal sites of involvement include oral, genital, ocular, otic, esophageal, and, less commonly, bladder, nasal, laryngeal, and anal surfaces. Oral lichen planus is a mucosal variant of lichen planus, which tends to affect women more often than men, with a typically more chronic course and potential for significant morbidity. Treatment can be challenging, and there is potentially a low risk of malignant transformation; however, therapeutic benefits can be obtained with various topical and systemic medications. Clinical monitoring is recommended to ensure symptomatic control. Increasing awareness and recognition of this entity have continued to fuel advances in therapy and in our understanding of the disease. PMID:27343965

  16. A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma.

    PubMed

    Lai, Jun; Zhou, Zhan; Tang, Xiao-Jing; Gao, Zhi-Bin; Zhou, Jie; Chen, Shu-Qing

    2016-05-14

    Malignant peritoneal mesothelioma (MPM) is an aggressive rare malignancy associated with asbestos exposure. A better understanding of the molecular pathogenesis of MPM will help develop a targeted therapy strategy. Oncogene targeted depth sequencing was performed on a tumor sample and paired peripheral blood DNA from a patient with malignant mesothelioma of the peritoneum. Four somatic base-substitutions in NOTCH2, NSD1, PDE4DIP, and ATP10B and 1 insert frameshift mutation in BAP1 were validated by the Sanger method at the transcriptional level. A 13-amino acids neo-peptide of the truncated Bap1 protein, which was produced as a result of this novel frameshift mutation, was predicted to be presented by this patient's HLA-B protein. The polyclonal antibody of the synthesized 13-mer neo-peptide was produced in rabbits. Western blotting results showed a good antibody-neoantigen specificity, and Immunohistochemistry (IHC) staining with the antibody of the neo-peptide clearly differentiated neoplastic cells from normal cells. A search of the Catalogue of Somatic Mutations in Cancer (COSMIC) database also revealed that 53.2% of mutations in BAP1 were frameshift indels with neo-peptide formation. An identified tumor-specific neo-antigen could be the potential molecular biomarker for personalized diagnosis to precisely subtype rare malignancies such as MPM.

  17. A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma

    PubMed Central

    Lai, Jun; Zhou, Zhan; Tang, Xiao-Jing; Gao, Zhi-Bin; Zhou, Jie; Chen, Shu-Qing

    2016-01-01

    Malignant peritoneal mesothelioma (MPM) is an aggressive rare malignancy associated with asbestos exposure. A better understanding of the molecular pathogenesis of MPM will help develop a targeted therapy strategy. Oncogene targeted depth sequencing was performed on a tumor sample and paired peripheral blood DNA from a patient with malignant mesothelioma of the peritoneum. Four somatic base-substitutions in NOTCH2, NSD1, PDE4DIP, and ATP10B and 1 insert frameshift mutation in BAP1 were validated by the Sanger method at the transcriptional level. A 13-amino acids neo-peptide of the truncated Bap1 protein, which was produced as a result of this novel frameshift mutation, was predicted to be presented by this patient’s HLA-B protein. The polyclonal antibody of the synthesized 13-mer neo-peptide was produced in rabbits. Western blotting results showed a good antibody-neoantigen specificity, and Immunohistochemistry (IHC) staining with the antibody of the neo-peptide clearly differentiated neoplastic cells from normal cells. A search of the Catalogue of Somatic Mutations in Cancer (COSMIC) database also revealed that 53.2% of mutations in BAP1 were frameshift indels with neo-peptide formation. An identified tumor-specific neo-antigen could be the potential molecular biomarker for personalized diagnosis to precisely subtype rare malignancies such as MPM. PMID:27187383

  18. Intraoral malignant melanoma

    PubMed Central

    Babburi, Suresh; Subramanyam, R. V.; Aparna, V.; Sowjanya, P.

    2013-01-01

    Primary oral mucosal melanoma is a rare aggressive neoplasm and accounts for only 0.2-8% of all reported melanomas. It is a malignant neoplasm of melanocytes that may arise from a benign melanocytic lesion or de novo from melanocytes within normal skin or mucosa. It is considered to be the most deadly and biologically unpredictable of all human neoplasms, having the worst prognosis. In this article, we report a case of oral melanoma in a 52-year-old female patient with a chief complaint of black discolouration of the maxillary gingiva and palate. PMID:24249959

  19. Differences in allergenic potential of food extracts following oral exposure in mice reflect differences in digestibility: potential approaches to safety assessment.

    PubMed

    Bowman, Christal C; Selgrade, Maryjane K

    2008-03-01

    An animal model for food allergy is needed to assess genetically modified food crops for potential allergenicity. The ideal model must produce allergic antibody (IgE) to proteins differentially according to known allergenicity before being used to accurately identify potential allergens among novel proteins. The oral route is the most relevant for exposure to food antigens, and a protein's stability to digestion is a current risk assessment tool based on this natural route. However, normal laboratory animals do not mount allergic responses to proteins administered orally due to oral tolerance, an immunologic mechanism which specifically suppresses IgE. To circumvent oral tolerance and evoke differential IgE responses to a panel of allergenic and nonallergenic food extracts, female C3H/HeJ mice were exposed subcutaneously or orally with cholera toxin as an adjuvant. All foods elicited IgE by the subcutaneous route. Oral exposure, however, resulted in IgE to allergens (peanut, Brazil nut, and egg white) but not to nonallergens (spinach and turkey), provided that the dose and exposures were limited. Additionally, in vitro digestibility assays demonstrated the presence of digestion-stable proteins in the allergenic food extracts but not in the nonallergenic foods. Our results suggest that the subcutaneous route is inadequate to distinguish allergens from nonallergens, but oral exposure under the appropriate experimental conditions will result in differential allergic responses in accordance with known allergenicity. Moreover, those foods containing digestion-resistant proteins provoke allergic responses in this model, supporting the current use of pepsin resistance in the decision tree for potential allergenicity assessment.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the recent investigation of malignant catarrhal fever (MCF) in a red brocket deer (Mazama americana) from a Texas zoo, the MCF viral DNA from the newly recognized herpesvirus causing disease in white-tailed deer (Odocoileus virginianus) (termed MCFV-WTD) was detected. The epidemiology information...

  1. Pseudoepitheliomatous Hyperplasia: Relevance in Oral Pathology.

    PubMed

    Sarangarajan, R; Vedam, V K Vaishnavi; Sivadas, G; Krishnaraj, R; Sarangarajan, Anuradha; Shanmugam, K T

    2015-07-01

    Pseudoepitheliomatous hyperplasia (PEH), a neglected entity by oral pathologist possesses utmost importance in the field of research. Of all the investigative challenges, PEH, a reactive epithelial proliferation is seen secondary to lesions with infectious, inflammatory, reactive, and degenerative origin. Small sized samples, incomplete excision, improper orientation, and dense inflammatory changes render diagnostic confront to the oral pathologist in exclusion of frankly invasive malignant lesions like squamous cell carcinoma from lesions exhibiting PEH. The diagnosis can occasionally be difficult as they mimic other lesions also, on clinic-pathological assessment. Thus, this article gives an insight regarding the various concepts of etiopathogenesis, histopathology, differential diagnosis, and malignant potential of PEH. A combined effort of a clinician and pathologist benefits every patient to rule out malignancy and render appropriate treatment as the only local conservative approach is essential to remove PEH associated lesions.

  2. Pseudoepitheliomatous Hyperplasia: Relevance in Oral Pathology

    PubMed Central

    Sarangarajan, R; Vedam, V K Vaishnavi; Sivadas, G; Krishnaraj, R; Sarangarajan, Anuradha; Shanmugam, K T

    2015-01-01

    Pseudoepitheliomatous hyperplasia (PEH), a neglected entity by oral pathologist possesses utmost importance in the field of research. Of all the investigative challenges, PEH, a reactive epithelial proliferation is seen secondary to lesions with infectious, inflammatory, reactive, and degenerative origin. Small sized samples, incomplete excision, improper orientation, and dense inflammatory changes render diagnostic confront to the oral pathologist in exclusion of frankly invasive malignant lesions like squamous cell carcinoma from lesions exhibiting PEH. The diagnosis can occasionally be difficult as they mimic other lesions also, on clinic-pathological assessment. Thus, this article gives an insight regarding the various concepts of etiopathogenesis, histopathology, differential diagnosis, and malignant potential of PEH. A combined effort of a clinician and pathologist benefits every patient to rule out malignancy and render appropriate treatment as the only local conservative approach is essential to remove PEH associated lesions. PMID:26229388

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

    SciTech Connect

    Liauw, Stanley L.; Sylvester, John E. . E-mail: johnsylvester@seattleprostateinst.com; Morris, Christopher G.; Blasko, John C.; Grimm, Peter D.

    2006-11-01

    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.

  4. Chromosome 3 anomalies investigated by genome wide SNP analysis of benign, low malignant potential and low grade ovarian serous tumours.

    PubMed

    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

    2011-01-01

    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

  5. Global acetylation and methylation changes predict papillary urothelial neoplasia of low malignant potential recurrence: a quantitative analysis.

    PubMed

    Mazzucchelli, R; Scarpelli, M; Lopez-Beltran, A; Cheng, L; Bartels, H; Bartels, P H; Alberts, D S; Montironi, R

    2011-01-01

    Papillary urothelial neoplasia of low malignant potential (PUNLMP) recurs in approximately 35% of patients. Conventional histopathological assessment does not distinguish non-recurrent from recurrent PUNLMP. The aim of this study is to explore the differences in global histone acetylation and global DNA methylation between non-recurrent and recurrent PUNLMP. Acetylated histone H3 lysine 9 (AcH3K9) and 5-methylcytosine (5MeC) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). The total optical density of the nuclear staining was measured photometrically in at least 40 nuclei separately for the basal, intermediate and luminal positions in each case. Concerning the total optical density values for both acetylation and methylation, a decrease in staining is observed from non-recurrent PUNLMP to recurrent PUNLMP, at all nuclear locations. For acetylation the mean value in non-recurrent PUNLMP, intermediate between NU and UC, is closer to the former than to latter. The mean value in recurrent PUNLMP is closer to UC than to NU. In NU, non-recurrent and recurrent PUNLMP, the acetylation to methylation ratio decreased from the nuclei in basal position to those in the surface, the average for the above groups being 1.491, 1.611 and 1.746, respectively. Setting the observed values for NU at each sampling location to unity, acetylation shows a steady decrease, the percentages of changes in this nuclear location compared to NU being -5% in non-recurrent PUNLMP, -15% in recurrent PUNLMP and -24% in UC. Concerning methylation, there is a slight increase in non-recurrent PUNLMP (+5%), a decrease in recurrent PUNLMP (-19%) followed by a sharp rise for the UC (+61%). In conclusion, there are differences in global histone acetylation and DNA methylation patterns between non-recurrent and recurrent PUNLMP. Further studies are needed

  6. Immunohistochemical evaluation of global DNA methylation and histone acetylation in papillary urothelial neoplasm of low malignant potential.

    PubMed

    Barbisan, F; Mazzucchelli, R; Santinelli, A; Stramazzotti, D; Scarpelli, M; Lopez-Beltran, A; Cheng, L; Montironi, R

    2008-01-01

    A preceding study has shown that karyometry detected subvisual differences in chromatin organization status between non-recurrent and recurrent papillary urothelial neoplasm of low malignant potential (PUNLMP). The status of chromatin organization depends on epigenetic events, such as DNA methylation and histone acetylation. The aim of this study is to explore global DNA methylation and global histone acetylation in non-recurrent and recurrent PUNLMP. 5-methylcytosine (5MeC) and acetylated histone H3 lysine 9 (AcH3K9) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). For global DNA methylation, the mean percentage of positive nuclei in the cells adjacent to the stroma increased from NU (79%) through non-recurrent and recurrent PUNLMP (86% and 93%, respectively) to UC (97%). The percentages of positive nuclei in the intermediate cell layers and in the superficial cells in the four groups were similar to those adjacent to the stroma. The proportion of nuclei with weak-to-moderate intensity was far greater than that of those strongly stained and increased steadily from NU to UC. For global histone acetylation, the mean percentage of positive nuclei was highest in non-recurrent PUNLMP (i.e. 90%) and lowest in recurrent PUNLMP (i.e. 81%). In NU and UC the mean percentages of positive nuclei were 84% and 86%, respectively. The percentage of positive nuclei decreased from the cell layer adjacent to the stroma to the superficial cell layer. The proportion of nuclei with weak-to-moderate intensity was slightly greater than that of those strongly stained. In comparison with global DNA methylation, the proportion of strongly stained nuclei was much higher. In conclusion, there are differences in global DNA methylation and histone acetylation patterns between non-recurrent and recurrent PUNLMP. Further studies are needed to

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

    PubMed Central

    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.

    2011-01-01

    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

  8. Classification of Extraovarian Implants in Patients With Ovarian Serous Borderline Tumors (Tumors of Low Malignant Potential) Based on Clinical Outcome.

    PubMed

    McKenney, Jesse K; Gilks, C Blake; Kalloger, Steve; Longacre, Teri A

    2016-09-01

    The classification of extraovarian disease into invasive and noninvasive implants predicts patient outcome in patients with high-stage ovarian serous borderline tumors (tumors of low malignant potential). However, the morphologic criteria used to classify implants vary between studies. To date, there has been no large-scale study with follow-up data comparing the prognostic significance of competing criteria. Peritoneal and/or lymph node implants from 181 patients with high-stage serous borderline tumors were evaluated independently by 3 pathologists for the following 8 morphologic features: micropapillary architecture; glandular architecture; nests of epithelial cells with surrounding retraction artifact set in densely fibrotic stroma; low-power destructive tissue invasion; single eosinophilic epithelial cells within desmoplastic stroma; mitotic activity; nuclear pleomorphism; and nucleoli. Follow-up of 156 (86%) patients ranged from 11 to 264 months (mean, 89 mo; median, 94 mo). Implants with low-power destructive invasion into underlying tissue were the best predictor of adverse patient outcome with 69% overall and 59% disease-free survival (P<0.01). In the evaluation of individual morphologic features, the low-power destructive tissue invasion criterion also had excellent reproducibility between observers (κ=0.84). Extraovarian implants with micropapillary architecture or solid nests with clefts were often associated with tissue invasion but did not add significant prognostic value beyond destructive tissue invasion alone. Implants without attached normal tissue were not associated with adverse outcome and appear to be noninvasive. Because the presence of invasion in an extraovarian implant is associated with an overall survival analogous to that of low-grade serous carcinoma, the designation low-grade serous carcinoma is recommended. Even though the low-power destructive tissue invasion criterion has excellent interobserver reproducibility, it is further

  9. Long-term low-dose α-particle enhanced the potential of malignant transformation in human bronchial epithelial cells through MAPK/Akt pathway

    SciTech Connect

    Liu, Weili; Xiao, Linlin; Dong, Chen; He, Mingyuan; Pan, Yan; Xie, Yuexia; Tu, Wenzhi; Fu, Jiamei; Shao, Chunlin

    2014-05-09

    Highlights: • Multi-exposures of 25 mGy α-ray enhanced cell proliferation, adhesion, and invasion. • MAPK/Akt but not JNK/P66 was positively correlated with cell invasive phenotypes. • LDR of α-irradiation triggers cell malignant transformation through MAPK/Akt. - Abstract: Since the wide usage of ionizing radiation, the cancer risk of low dose radiation (LDR) (<0.1 Gy) has become attractive for a long time. However, most results are derived from epidemiologic studies on atomic-bomb survivors and nuclear accidents surrounding population, and the molecular mechanism of this risk is elusive. To explore the potential of a long-term LDR-induced malignant transformation, human bronchial epithelial cells Beas-2B were fractionally irradiated with 0.025 Gy α-particles for 8 times in total and then further cultured for 1–2 months. It was found that the cell proliferation, the abilities of adhesion and invasion, and the protein expressions of p-ERK, p-Akt, especially p-P38 were not only increased in the multiply-irradiated cells but also in their offspring 1–2 months after the final exposure, indicating high potentiality of cell malignant transformation. On opposite, the expressions of p-JNK and p-P66 were diminished in the subcultures of irradiated cells and thus may play a role of negative regulation in canceration. When the cells were transferred with p38 siRNA, the LDR-induced enhancements of cell adhesion and invasion were significantly reduced. These findings suggest that long-term LDR of α-particles could enhance the potential of malignant transformation incidence in human bronchial epithelial cells through MAPK/Akt pathway.

  10. Antibacterial potential of Manuka honey against three oral bacteria in vitro.

    PubMed

    Schmidlin, PatrickSchmidlin R; English, Helen; Duncan, Warwick; Belibasakis, Georgios N; Thurnheer, Thomas

    2014-01-01

    Honey is an ancient natural remedy for the treatment of infected wounds. It has regained attention in the medical profession, as it has recently been reported to have a broad-spectrum inhibitory effect against bacteria. Data concerning Manuka honey of New Zealand origin, which is claimed to provide additional non-peroxide antimicrobial activity (so-called standard NPA) against oral pathogens, is still scarce. Therefore, this study aimed to screen for the antibacterial efficacy of different Manuka honey products against S. mutans (OMZ 918), P. gingivalis (OMZ 925) and A. actinomycetemcomitans (OMZ 299). Chlorhexidine and saline served as positive and negative controls, respectively, whereas a Swiss multifloral honey served as control honey without intrinsic non-peroxide activity. Chlorhexidine showed the highest inhibiting potential against all specimens tested. Manuka honey below an NPA value of 15 showed the least bacterial growth-inhibiting potential, even less – although not significantly so – than multifloral Swiss honey. Manuka honey above an NPA value of 15 showed a significantly higher antibacterial effect compared to the other honeys tested. All Manuka honey preparations were more effective in inhibiting the growth of P. gingivalis and A. actinomycetemcomitans, rather than S. mutans. In conclusion, the study showed an NPA dose-dependent antibacterial efficacy of Manuka honey. Further investigations of this natural product are now open for scrutiny. PMID:25253413

  11. Caffeic Acid phenethyl ester is a potential therapeutic agent for oral cancer.

    PubMed

    Kuo, Ying-Yu; Jim, Wai-Tim; Su, Liang-Cheng; Chung, Chi-Jung; Lin, Ching-Yu; Huo, Chieh; Tseng, Jen-Chih; Huang, Shih-Han; Lai, Chih-Jen; Chen, Bo-Chih; Wang, Bi-Juan; Chan, Tzu-Min; Lin, Hui-Ping; Chang, Wun-Shaing Wayne; Chang, Chuang-Rung; Chuu, Chih-Pin

    2015-01-01

    Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the most common type of head and neck cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC). The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs. In this review we discuss the possibility of using caffeic acid phenethyl ester (CAPE) as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-κB function, as well as activity of matrix metalloproteinase (MMPs), epidermal growth factor receptor (EGFR), and Cyclooxygenase-2 (COX-2). Therefore, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells. According to the evidence that aberrations in the EGFR/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling, NF-κB function, COX-2 activity, and MMPs activity are frequently found in oral cancers, and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer patient survival and clinical progression, we believe that CAPE treatment will be useful for treatment of advanced oral cancer patients. PMID:25984601

  12. Antibacterial peptide nisin: a potential role in the inhibition of oral pathogenic bacteria.

    PubMed

    Tong, Zhongchun; Ni, Longxing; Ling, Junqi

    2014-10-01

    Although the antimicrobial peptide nisin has been extensively studied in the food industry for decades, its application in the oral cavity remains to develop and evaluate its feasibility in treating oral common diseases. Nisin is an odorless, colorless, tasteless substance with low toxicity and with antibacterial activities against Gram-positive bacteria. These biologic properties may establish its use in promising products for oral diseases. This article summarizes the antibacterial efficiency of nisin against pathogenic bacteria related to dental caries and root canal infection and discusses the combination of nisin and common oral drugs.

  13. Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer

    PubMed Central

    Kuo, Ying-Yu; Jim, Wai-Tim; Su, Liang-Cheng; Chung, Chi-Jung; Lin, Ching-Yu; Huo, Chieh; Tseng, Jen-Chih; Huang, Shih-Han; Lai, Chih-Jen; Chen, Bo-Chih; Wang, Bi-Juan; Chan, Tzu-Min; Lin, Hui-Ping; Chang, Wun-Shaing Wayne; Chang, Chuang-Rung; Chuu, Chih-Pin

    2015-01-01

    Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the most common type of head and neck cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC). The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs. In this review we discuss the possibility of using caffeic acid phenethyl ester (CAPE) as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-κB function, as well as activity of matrix metalloproteinase (MMPs), epidermal growth factor receptor (EGFR), and Cyclooxygenase-2 (COX-2). Therefore, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells. According to the evidence that aberrations in the EGFR/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling, NF-κB function, COX-2 activity, and MMPs activity are frequently found in oral cancers, and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer patient survival and clinical progression, we believe that CAPE treatment will be useful for treatment of advanced oral cancer patients. PMID:25984601

  14. Antibacterial peptide nisin: a potential role in the inhibition of oral pathogenic bacteria.

    PubMed

    Tong, Zhongchun; Ni, Longxing; Ling, Junqi

    2014-10-01

    Although the antimicrobial peptide nisin has been extensively studied in the food industry for decades, its application in the oral cavity remains to develop and evaluate its feasibility in treating oral common diseases. Nisin is an odorless, colorless, tasteless substance with low toxicity and with antibacterial activities against Gram-positive bacteria. These biologic properties may establish its use in promising products for oral diseases. This article summarizes the antibacterial efficiency of nisin against pathogenic bacteria related to dental caries and root canal infection and discusses the combination of nisin and common oral drugs. PMID:25088158

  15. Circulating miR-223 in Oral Cancer: Its Potential as a Novel Diagnostic Biomarker and Therapeutic Target

    PubMed Central

    Tachibana, Hirohiko; Sho, Ri; Takeda, Yuji; Zhang, Xuhong; Yoshida, Yukie; Narimatsu, Hiroto; Otani, Katsumi; Ishikawa, Shigeo; Fukao, Akira; Asao, Hironobu; Iino, Mitsuyoshi

    2016-01-01

    Circulating microRNAs (miRNAs) have been detected in various types of cancer and have been proposed as novel biomarkers for diagnosis and treatment. Until recently, however, no studies had comprehensively examined circulating miRNAs in oral cancer. The current study used an ultra-sensitive genome-wide miRNA array to investigate changes in circulating miRNAs in plasma from five patients with oral cancer and ten healthy individuals. Results indicated that there were only a few circulating miRNAs, including miR-223, miR-26a, miR-126, and miR-21, that were up-regulated in patients with oral cancer. A subsequent validation test indicated that circulating miR-223 levels were significantly higher (~2-fold, P< 0.05) in patients with oral cancer (n = 31) than in those without cancer (n = 31). Moreover, miR-223 was found to be up-regulated in tumor-adjacent normal tissue compared to tumor tissue from patients with oral cancer. A gain-of-function assay was performed to explore the potential roles of circulating miR-223 in the development of oral cancer. Results revealed that miR-223 functions as a tumor suppressor by inhibiting cell proliferation and inducing apoptosis. In conclusion, this study suggested that circulating miR-223 may serve as a potential biomarker for diagnosis and that it may represent a novel therapeutic target for treatment of oral cancer. PMID:27441818

  16. Potential therapeutic targets for oral cancer: ADM, TP53, EGFR, LYN, CTLA4, SKIL, CTGF, CD70.

    PubMed

    Bundela, Saurabh; Sharma, Anjana; Bisen, Prakash S

    2014-01-01

    In India, oral cancer has consistently ranked among top three causes of cancer-related deaths, and it has emerged as a top cause for the cancer-related deaths among men. Lack of effective therapeutic options is one of the main challenges in clinical management of oral cancer patients. We interrogated large pool of samples from oral cancer gene expression studies to identify potential therapeutic targets that are involved in multiple cancer hallmark events. Therapeutic strategies directed towards such targets can be expected to effectively control cancer cells. Datasets from different gene expression studies were integrated by removing batch-effects and was used for downstream analyses, including differential expression analysis. Dependency network analysis was done to identify genes that undergo marked topological changes in oral cancer samples when compared with control samples. Causal reasoning analysis was carried out to identify significant hypotheses, which can explain gene expression profiles observed in oral cancer samples. Text-mining based approach was used to detect cancer hallmarks associated with genes significantly expressed in oral cancer. In all, 2365 genes were detected to be differentially expressed genes, which includes some of the highly differentially expressed genes like matrix metalloproteinases (MMP-1/3/10/13), chemokine (C-X-C motif) ligands (IL8, CXCL-10/-11), PTHLH, SERPINE1, NELL2, S100A7A, MAL, CRNN, TGM3, CLCA4, keratins (KRT-3/4/13/76/78), SERPINB11 and serine peptidase inhibitors (SPINK-5/7). XIST, TCEAL2, NRAS and FGFR2 are some of the important genes detected by dependency and causal network analysis. Literature mining analysis annotated 1014 genes, out of which 841 genes were statistically significantly annotated. The integration of output of various analyses, resulted in the list of potential therapeutic targets for oral cancer, which included targets such as ADM, TP53, EGFR, LYN, CTLA4, SKIL, CTGF and CD70.

  17. Human papillomavirus DNA in oral mucosal lesions.

    PubMed

    Giovannelli, Lucia; Campisi, Giuseppina; Lama, Anna; Giambalvo, Ornella; Osborn, John; Margiotta, Valerio; Ammatuna, Pietro

    2002-03-15

    This study determined the presence of human papillomavirus (HPV) DNA in oral mucosa cells from 121 patients with different types of oral mucosal lesions (13 squamous cell carcinomas, 59 potentially malignant lesions, 49 benign erosive ulcerative lesions) and from 90 control subjects. HPV DNA was detected by nested polymerase chain reaction, and genotype was determined by DNA sequencing. HPV prevalence was 61.5% in carcinomas, 27.1% in potentially malignant lesions, 26.5% in erosive ulcerative lesions, and 5.5% in control subjects. The risk of malignant or potentially malignant lesions was associated with HPV and was statistically significant. HPV-18 was found in 86.5% of HPV-positive lesions but was not associated with a particular type of lesion and was found in 80% of the HPV-positive control subjects. HPV infection was related to older age but not to sex, smoking, or alcohol use; the presence of lesions in the oral cavity increased the risk of HPV infection.

  18. Adenovirus-mediated suppression of HMGI(Y) protein synthesis as potential therapy of human malignant neoplasias

    PubMed Central

    Scala, Stefania; Portella, Giuseppe; Fedele, Monica; Chiappetta, Gennaro; Fusco, Alfredo

    2000-01-01

    High mobility group I (HMGI) proteins are overexpressed in several human malignant tumors. We previously demonstrated that inhibition of HMGI synthesis prevents thyroid cell transformation. Here, we report that an adenovirus carrying the HMGI(Y) gene in an antisense orientation (Ad-Yas) induced programmed cell death of two human thyroid anaplastic carcinoma cell lines (ARO and FB-1), but not normal thyroid cells. The Ad-Yas virus led to death of lung, colon, and breast carcinoma cells. A control adenovirus carrying the lacZ gene did not inhibit the growth of either normal or neoplastic cells. Ad-Yas treatment of tumors induced in athymic mice by ARO cells caused a drastic reduction in tumor size. Therefore, suppression of HMGI(Y) protein synthesis by an HMGI(Y) antisense adenoviral vector may be a useful treatment strategy in a variety of human malignant neoplasias, in which HMGI(Y) gene overexpression is a general event. PMID:10759549

  19. Areca nut and its role in oral submucous fibrosis.

    PubMed

    Prabhu, Rachana V; Prabhu, Vishnudas; Chatra, Laxmikanth; Shenai, Prashant; Suvarna, Nithin; Dandekeri, Savita

    2014-12-01

    Areca nut, commonly called as betel nut or supari, is a fruit of areca catechu palm tree, which is native of South Asia and Pacific Islands. The seed or endosperm is consumed fresh, boiled or after sun drying or curing. Chewing areca nut is thought to have central nervous system stimulating effect and along with this it is known to have salivary stimulating and digestive properties. According to the traditional Ayurvedic medicine, chewing areca nut and betel leaf is a good remedy against halitosis. It is also used for its deworming property. Along with these beneficial effects of areca nut one of its most harmful effects on the human body in general and oral cavity in particular is the development of potentially malignant disorder called Oral Submucous Fibrosis. The present paper discusses in detail the effects of the components of areca nut on pathogenesis of Oral Submucous Fibrosis. Key words:Areca nut, oral submucous fibrosis, potentially malignant disorder, supari. PMID:25674328

  20. Areca nut and its role in oral submucous fibrosis

    PubMed Central

    Prabhu, Vishnudas; Chatra, Laxmikanth; Shenai, Prashant; Suvarna, Nithin; Dandekeri, Savita

    2014-01-01

    Areca nut, commonly called as betel nut or supari, is a fruit of areca catechu palm tree, which is native of South Asia and Pacific Islands. The seed or endosperm is consumed fresh, boiled or after sun drying or curing. Chewing areca nut is thought to have central nervous system stimulating effect and along with this it is known to have salivary stimulating and digestive properties. According to the traditional Ayurvedic medicine, chewing areca nut and betel leaf is a good remedy against halitosis. It is also used for its deworming property. Along with these beneficial effects of areca nut one of its most harmful effects on the human body in general and oral cavity in particular is the development of potentially malignant disorder called Oral Submucous Fibrosis. The present paper discusses in detail the effects of the components of areca nut on pathogenesis of Oral Submucous Fibrosis. Key words:Areca nut, oral submucous fibrosis, potentially malignant disorder, supari. PMID:25674328

  1. Potential of Text-Based Internet Chats for Improving Oral Fluency in a Second Language

    ERIC Educational Resources Information Center

    Blake, Christopher

    2009-01-01

    Although a number of studies have reported on the positive effects of Internet chats in the second language classroom, to the best of my knowledge no studies to date have examined the effect of text-based chats on oral fluency development. This exploratory study addressed the above question by examining the oral fluency development of 34 English…

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

    PubMed

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

    2012-03-01

    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.

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

    PubMed

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

    2012-03-01

    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

  4. Therapeutic potential of an orally effective small molecule inhibitor of plasminogen activator inhibitor for asthma.

    PubMed

    Liu, Rui-Ming; Eldridge, Stephanie; Watanabe, Nobuo; Deshane, Jessy; Kuo, Hui-Chien; Jiang, Chunsun; Wang, Yong; Liu, Gang; Schwiebert, Lisa; Miyata, Toshio; Thannickal, Victor J

    2016-02-15

    Asthma is one of the most common respiratory diseases. Although progress has been made in our understanding of airway pathology and many drugs are available to relieve asthma symptoms, there is no cure for chronic asthma. Plasminogen activator inhibitor 1 (PAI-1), a primary inhibitor of tissue-type and urokinase-type plasminogen activators, has pleiotropic functions besides suppression of fibrinolysis. In this study, we show that administration of TM5275, an orally effective small-molecule PAI-1 inhibitor, 25 days after ovalbumin (OVA) sensitization-challenge, significantly ameliorated airway hyperresponsiveness in an OVA-induced chronic asthma model. Furthermore, we show that TM5275 administration significantly attenuated OVA-induced infiltration of inflammatory cells (neutrophils, eosinophils, and monocytes), the increase in the levels of OVA-specific IgE and Th2 cytokines (IL-4 and IL-5), the production of mucin in the airways, and airway subepithelial fibrosis. Together, the results suggest that the PAI-1 inhibitor TM5275 may have therapeutic potential for asthma through suppressing eosinophilic allergic response and ameliorating airway remodeling. PMID:26702150

  5. Antitumor potential of three herbal extracts against human oral squamous cell lines.

    PubMed

    Chu, Qing; Satoh, Kazue; Kanamoto, Taisei; Terakubo, Shigemi; Nakashima, Hideki; Wang, Qintao; Sakagami, Hiroshi

    2009-08-01

    Three Chinese herbal extracts of Drynaria baronii, Angelica sinensis and Cornus officinalis Sieb. et Zucc (referred to as DB, AS, CO, respectively) were investigated for their antitumor potential. These extracts showed very weak cytotoxicity against all nine cultured human cells (normal and tumor cells), but with some tumor-specific cytotoxicity displayed by DB and CO. These extracts showed little or no growth stimulation effects at lower concentrations (so-called 'hormetic effect'). Human oral squamous cell carcinoma cell lines (HSC-2, NA) were relatively resistant to committing apoptosis, as compared with human promyelocytic leukemia HL-60 cells. Electron-spin resonance spectroscopy shows that DB and CO scavenged superoxide anion (generated by hypoxanthine and xanthine oxidase reaction) and hydroxyl radical (generated by Fenton reaction) more efficiently than AS. DB and CO, but not AS, produced broad radical peak(s) and enhanced the superoxide scavenging activity of vitamin C. However, none of the extracts clearly enhanced the cytotoxicity of mitoxantrone, an anthracycline antitumor antibiotic. DB, but not CO and AS, showed weak anti-HIV activity. These data demonstrate several unique antitumor properties of DB. PMID:19661337

  6. Therapeutic potential of an orally effective small molecule inhibitor of plasminogen activator inhibitor for asthma.

    PubMed

    Liu, Rui-Ming; Eldridge, Stephanie; Watanabe, Nobuo; Deshane, Jessy; Kuo, Hui-Chien; Jiang, Chunsun; Wang, Yong; Liu, Gang; Schwiebert, Lisa; Miyata, Toshio; Thannickal, Victor J

    2016-02-15

    Asthma is one of the most common respiratory diseases. Although progress has been made in our understanding of airway pathology and many drugs are available to relieve asthma symptoms, there is no cure for chronic asthma. Plasminogen activator inhibitor 1 (PAI-1), a primary inhibitor of tissue-type and urokinase-type plasminogen activators, has pleiotropic functions besides suppression of fibrinolysis. In this study, we show that administration of TM5275, an orally effective small-molecule PAI-1 inhibitor, 25 days after ovalbumin (OVA) sensitization-challenge, significantly ameliorated airway hyperresponsiveness in an OVA-induced chronic asthma model. Furthermore, we show that TM5275 administration significantly attenuated OVA-induced infiltration of inflammatory cells (neutrophils, eosinophils, and monocytes), the increase in the levels of OVA-specific IgE and Th2 cytokines (IL-4 and IL-5), the production of mucin in the airways, and airway subepithelial fibrosis. Together, the results suggest that the PAI-1 inhibitor TM5275 may have therapeutic potential for asthma through suppressing eosinophilic allergic response and ameliorating airway remodeling.

  7. Cancer stem cells - new and potentially important targets for the therapy of oral squamous cell carcinoma.

    PubMed

    Costea, D E; Tsinkalovsky, O; Vintermyr, O K; Johannessen, A C; Mackenzie, I C

    2006-09-01

    There is increasing evidence that the growth and spread of cancers is driven by a small subpopulation of cancer stem cells (CSCs) - the only cells that are capable of long-term self-renewal and generation of the phenotypically diverse tumour cell population. Current failure of cancer therapies may be due to their lesser effect on potentially quiescent CSCs which remain vital and retain their full capacity to repopulate the tumour. Treatment strategies for the elimination of cancer therefore need to consider the consequences of the presence of CSCs. However, the development of new CSC-targeted strategies is currently hindered by the lack of reliable markers for the identification of CSCs and the poor understanding of their behaviour and fate determinants. Recent studies of cell lines derived from oral squamous cell carcinoma (OSCC) indicate the presence of subpopulations of cells with phenotypic and behavioural characteristics corresponding to both normal epithelial stem cells and to cells capable of initiating tumours in vivo. The present review discusses the relevance to OSCC of current CSC concepts, the state of various methods for CSC identification, characterization and isolation (clonal functional assay, cell sorting based on surface markers or uptake of Hoechst dye), and possible new approaches to therapy.

  8. Epigenetics in the hematologic malignancies

    PubMed Central

    Fong, Chun Yew; Morison, Jessica; Dawson, Mark A.

    2014-01-01

    A wealth of genomic and epigenomic data has identified abnormal regulation of epigenetic processes as a prominent theme in hematologic malignancies. Recurrent somatic alterations in myeloid malignancies of key proteins involved in DNA methylation, post-translational histone modification and chromatin remodeling have highlighted the importance of epigenetic regulation of gene expression in the initiation and maintenance of various malignancies. The rational use of targeted epigenetic therapies requires a thorough understanding of the underlying mechanisms of malignant transformation driven by aberrant epigenetic regulators. In this review we provide an overview of the major protagonists in epigenetic regulation, their aberrant role in myeloid malignancies, prognostic significance and potential for therapeutic targeting. PMID:25472952

  9. p53 Expression Helps Identify High Risk Oral Tongue Pre- malignant Lesions and Correlates with Patterns of Invasive Tumour Front and Tumour Depth in Oral Tongue Squamous Cell Carcinoma Cases.

    PubMed

    Viveka, Thangaraj Soundara; Shyamsundar, Vidyarani; Krishnamurthy, Arvind; Ramani, Pratibha; Ramshankar, Vijayalakshmi

    2016-01-01

    Oral tongue squamous cell carcinoma (OTSCC) is the most common oral cancer subtype with a maximum propensity for regional spread. Our objective was to study if p53 expression might have any correlation with aggressive patterns of invasion within oral tongue cancers as well as with the histologically identified degree of oral tongue dysplasia. p53 immunoexpression was studied using immunohistochemistry in early staged OTSCCs (n=155), oral tongue dysplasias, (n=29) and oral tongue normal specimens (n=10) and evaluated for correlations with histological and clinicopathological parameters. Our study (n=194) showed a pattern of p53 expression increasing with different grades of tongue dysplasia to different grades of invasive OTSCC (p=0.000). Among the OTSCC tumours, positive p53 expression was seen in 43.2% (67/155) and a higher p53 labelling index was significantly associated with increased Bryne's grade of the tumour invasive front (p=0.039) and increased tumour depth (p=0.018). Among the OTSCC patients with tobacco habits, (n=91), a higher p53 labelling index was significantly associated with increased risk of local recurrence (p=0.025) and with lymphovascular space involvement (p=0.014). Evaluation of p53 through varying degrees of dysplasia to oral tongue cancer indicates that p53 expression is linked to aggressive features of oral tongue cancers and tongue precancers entailing a closer monitoring in positive cases. Among the OTSCCs, p53 expression is associated with tumour aggressiveness correlating with increased grading of invasive tumour front and tumour depth.

  10. Stromal myofibroblasts in oral leukoplakia and oral squamous cell carcinoma

    PubMed Central

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

    2012-01-01

    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. PMID:22322518

  11. Malignant adenolymphoma.

    PubMed

    Moosavi, H; Ryan, C; Schwartz, S; Donnelly, J A

    1980-01-01

    Adenolymphoma (Warthin's tumor) is a well studied benign tumor of the salivary gland. Malignant transformation of such a tumor is rare and not well documented in the literature. The light microscopic and ultrastructural features of an undifferentiated carcinoma arising in an adenolymphoma in the parotid gland of a middle aged male are described, and the relevant literature is reviewed. Similarities between the benign adenolymphoma and the undifferentiated malignant tumor, such as the presence of interstitial lymphoplasmacytic cell infiltrates, dark and light epithelial cells, similar cytoplasmic organelles, and nuclear morphology, suggest a malignant transformation of a previously existing benign adenolymphoma.

  12. [Malignant hyperthermia].

    PubMed

    Metterlein, T; Schuster, F; Graf, B M; Anetseder, M

    2014-12-01

    Malignant hyperthermia (MH) is a rare hereditary, mostly subclinical myopathy. Trigger substances, such as volatile anesthetic agents and the depolarizing muscle relaxant succinylcholine can induce a potentially fatal metabolic increase in predisposed patients caused by a dysregulation of the myoplasmic calcium (Ca) concentration. Mutations in the dihydropyridine ryanodine receptor complex in combination with the trigger substances are responsible for an uncontrolled release of Ca from the sarcoplasmic reticulum. This leads to activation of the contractile apparatus and a massive increase in cellular energy production. Exhaustion of the cellular energy reserves ultimately results in local muscle cell destruction and subsequent cardiovascular failure. The clinical picture of MH episodes is very variable. Early symptoms are hypoxia, hypercapnia and cardiac arrhythmia whereas the body temperature rise, after which MH is named, often occurs later. Decisive for the course of MH episodes is a timely targeted therapy. Following introduction of the hydantoin derivative dantrolene, the previously high mortality of fulminant MH episodes could be reduced to well under 10 %. An MH predisposition can be detected using the invasive in vitro contracture test (IVCT) or mutation analysis. Few elaborate diagnostic procedures are in the developmental stage. PMID:25384957

  13. The potential of immobilized artificial membrane chromatography to predict human oral absorption.

    PubMed

    Tsopelas, Fotios; Vallianatou, Theodosia; Tsantili-Kakoulidou, Anna

    2016-01-01

    The potential of immobilized artificial membrane (IAM) chromatography to estimate human oral absorption (%HOA) was investigated. For this purpose, retention indices on IAM stationary phases reported previously by our group or measured by other authors under similar conditions were used to model %HOA data, compiled from literature sources. Considering the pH gradient in gastrointestinal tract, the highest logkw(IAM) values were considered, obtained either at pH7.4 or 5.5, defined as logkw(IAM)(best). Non linear models were established upon introduction of additional parameters and after exclusion of drugs which are substrates either to efflux or uptake transporters. The best model included Abraham's hydrogen-bond acidity parameter, molecular weight as well as the positively and negatively charged molecular fractions. For reasons of comparison between IAM chromatography and traditional lipophilicity, corresponding models were derived by replacing IAM retention factors with octanol-water distribution coefficients (logD). An overexpression of electrostatic interactions with phosphate anions was observed in the case of IAM retention as expressed by the negative contribution of the positively charged fraction F(+). The same parameter is statistically significant also in the logD model, but with a positive sign, indicating the attraction of basic drugs in the negatively charged inner membrane. To validate the obtained models a blind test set of 22 structurally diverse drugs was used, whose logkw(IAM)(best) values were determined and analyzed in the present study under similar conditions. IAM retention factors were further compared with MDCK cell lines permeability data taken from literature for a set of validation drugs. The overexpression of electrostatic interactions with phosphate anions on IAM surface was also evident in respect to MDCK permeability. In contrast to the clear classification between drugs with high and poor (or intermediate) absorption provided by MDCK

  14. The potential of immobilized artificial membrane chromatography to predict human oral absorption.

    PubMed

    Tsopelas, Fotios; Vallianatou, Theodosia; Tsantili-Kakoulidou, Anna

    2016-01-01

    The potential of immobilized artificial membrane (IAM) chromatography to estimate human oral absorption (%HOA) was investigated. For this purpose, retention indices on IAM stationary phases reported previously by our group or measured by other authors under similar conditions were used to model %HOA data, compiled from literature sources. Considering the pH gradient in gastrointestinal tract, the highest logkw(IAM) values were considered, obtained either at pH7.4 or 5.5, defined as logkw(IAM)(best). Non linear models were established upon introduction of additional parameters and after exclusion of drugs which are substrates either to efflux or uptake transporters. The best model included Abraham's hydrogen-bond acidity parameter, molecular weight as well as the positively and negatively charged molecular fractions. For reasons of comparison between IAM chromatography and traditional lipophilicity, corresponding models were derived by replacing IAM retention factors with octanol-water distribution coefficients (logD). An overexpression of electrostatic interactions with phosphate anions was observed in the case of IAM retention as expressed by the negative contribution of the positively charged fraction F(+). The same parameter is statistically significant also in the logD model, but with a positive sign, indicating the attraction of basic drugs in the negatively charged inner membrane. To validate the obtained models a blind test set of 22 structurally diverse drugs was used, whose logkw(IAM)(best) values were determined and analyzed in the present study under similar conditions. IAM retention factors were further compared with MDCK cell lines permeability data taken from literature for a set of validation drugs. The overexpression of electrostatic interactions with phosphate anions on IAM surface was also evident in respect to MDCK permeability. In contrast to the clear classification between drugs with high and poor (or intermediate) absorption provided by MDCK

  15. Detection and Isolation of Swine Influenza A Virus in Spiked Oral Fluid and Samples from Individually Housed, Experimentally Infected Pigs: Potential Role of Porcine Oral Fluid in Active Influenza A Virus Surveillance in Swine

    PubMed Central

    Decorte, Inge; Steensels, Mieke; Lambrecht, Bénédicte

    2015-01-01

    Background The lack of seasonality of swine influenza A virus (swIAV) in combination with the capacity of swine to harbor a large number of co-circulating IAV lineages, resulting in the risk for the emergence of influenza viruses with pandemic potential, stress the importance of swIAV surveillance. To date, active surveillance of swIAV worldwide is barely done because of the short detection period in nasal swab samples. Therefore, more sensitive diagnostic methods to monitor circulating virus strains are requisite. Methods qRT-PCR and virus isolations were performed on oral fluid and nasal swabs collected from individually housed pigs that were infected sequentially with H1N1 and H3N2 swIAV strains. The same methods were also applied to oral fluid samples spiked with H1N1 to study the influence of conservation time and temperature on swIAV infectivity and detectability in porcine oral fluid. Results All swIAV infected animals were found qRT-PCR positive in both nasal swabs and oral fluid. However, swIAV could be detected for a longer period in oral fluid than in nasal swabs. Despite the high detectability of swIAV in oral fluid, virus isolation from oral fluid collected from infected pigs was rare. These results are supported by laboratory studies showing that the PCR detectability of swIAV remains unaltered during a 24 h incubation period in oral fluid, while swIAV infectivity drops dramatically immediately upon contact with oral fluid (3 log titer reduction) and gets lost after 24 h conservation in oral fluid at ambient temperature. Conclusions Our data indicate that porcine oral fluid has the potential to replace nasal swabs for molecular diagnostic purposes. The difficulty to isolate swIAV from oral fluid could pose a drawback for its use in active surveillance programs. PMID:26431039

  16. Malignant hyperthermia.

    PubMed

    Brockhouse, R T

    1979-04-01

    A case has been presented that illustrates successful managment of a patient with suspected malignant hyperthermia. The causes of this disorder are uncertain. If screening procedures identify a patient as susceptible to this disorder, careful planning in the preoperative stage is indicated. Preparedness during the operative procedure for any emergency is mandatory. Early and effective treatment seems to be the only method of preventing mortality with patients experiencing malignant hyperthermia. PMID:285135

  17. Malignant oncocytoma.

    PubMed

    Laurian, N; Zohar, Y; Kende, L

    1977-09-01

    A case of malignant oncocytoma of the parotid gland in a 32-year-old male is presented. Ten months after parotidectomy an undifferentiated carcinoma, in which oncocytes still could be recognized, developed in the operated area. According to the literature available to us, this is the second reported case in which malignant transformation in a benign oncocytoma of the salivary gland has been observed.

  18. Epidermal growth factor receptor expression in different subtypes of oral lichenoid disease

    PubMed Central

    Cortés-Ramírez, Dionisio A.; Rodríguez-Tojo, María J.; Coca-Meneses, Juan C.; Marichalar-Mendia, Xabier

    2014-01-01

    The oral lichenoid disease (OLD) includes different chronic inflammatory processes such as oral lichen planus (OLP) and oral lichenoid lesions (OLL), both entities with controversial diagnosis and malignant potential. Epidermal growth factor receptor (EFGR) is an important oral carcinogenesis biomarker and overexpressed in several oral potentially malignant disorders. Objectives: To analyze the EGFR expression in the OLD to find differences between OLP and OLL, and to correlate it with the main clinical and pathological features. Material and Methods: Forty-four OLD cases were studied and classified according to their clinical (Group C1: only papular lesions / Group C2: papular and other lesions) and histopathological features (Group HT: OLP-typical / Group HC: OLP-compatible) based in previous published criteria. Standard immunohistochemical identification of EGFR protein was performed. Comparative and descriptive statistical analyses were performed. Results: Thirty-five cases (79.5%) showed EGFR overexpression without significant differences between clinical and histopathological groups (p<0.05). Histological groups showed significant differences in the EGFR expression pattern (p=0.016). Conlusions: All OLD samples showed high EGFR expression. The type of clinical lesion was not related with EGFR expression; however, there are differences in the EGFR expression pattern between histological groups that may be related with a different biological profile and malignant risk. Key words:Oral lichenoid disease, oral lichen planus, oral lichenoid lesion, oral carcinogenesis, EGFR. PMID:24880441

  19. Pharmacokinetics of orally administered terbinafine in African penguins (Spheniscus demersus) for potential treatment of aspergillosis.

    PubMed

    Bechert, Ursula; Christensen, J Mark; Poppenga, Robert; Le, Hang; Wyatt, Jeff; Schmitt, Todd

    2010-06-01

    The objective of this study was to determine the pharmacokinetic parameters of orally administered terbinafine hydrochloride based on 3, 7, and 15 mg/kg single- as well as multiple-dosage trials in order to calculate dosing requirements for potential treatment of aspergillosis in African penguins (Spheniscus demersus). Ten adult African penguins were used in each of these trials, with a 2-wk washout period between trials. Mean plasma concentrations of terbinafine peaked in approximately 4 hrs at 0.11 +/- 0.017 microg/ml (mean +/- SD) following administration of 3 mg/kg terbinafine, while 7 mg/kg and 15 mg/kg dosages resulted in peak plasma concentrations of 0.37 +/- 0.105 and 0.33 +/- 0.054 microg/ml, respectively. The volume of distribution increased with increasing dosages, being 37 +/- 28.5, 40 +/- 28.1, and 52 +/- 18.6 mg/L for 3, 7, and 15 mg/kg doses, respectively. The mean half-life was biphasic with initial terminal half-life (t(1/2)) values of 9.9 +/- 4.5, 17.2 +/- 4.9 and 16.9 +/- 5.4 hrs, for 3, 7, and 15 mg/kg doses, respectively. A rapid first elimination phase was followed by a slower second phase, and final elimination was estimated to be 136 +/- 9.7 and 131 +/- 9.9 hrs, for 7 and 15 mg/kg doses, respectively. Linearity was demonstrated for area under the curve but not for peak plasma concentrations for the three dosages used. Calculations based on pharmacokinetic parameter values indicate that a 15 mg/kg terbinafine q24h dosage regimen would result in steady-state trough plasma concentrations above the minimum inhibitory concentration (0.8-1.6 microg/ ml), and this dosage is recommended as a potential treatment option for aspergillosis in penguins. However, additional research is required to determine both treatment efficacy and safety. PMID:20597218

  20. Pharmacokinetics of orally administered terbinafine in African penguins (Spheniscus demersus) for potential treatment of aspergillosis.

    PubMed

    Bechert, Ursula; Christensen, J Mark; Poppenga, Robert; Le, Hang; Wyatt, Jeff; Schmitt, Todd

    2010-06-01

    The objective of this study was to determine the pharmacokinetic parameters of orally administered terbinafine hydrochloride based on 3, 7, and 15 mg/kg single- as well as multiple-dosage trials in order to calculate dosing requirements for potential treatment of aspergillosis in African penguins (Spheniscus demersus). Ten adult African penguins were used in each of these trials, with a 2-wk washout period between trials. Mean plasma concentrations of terbinafine peaked in approximately 4 hrs at 0.11 +/- 0.017 microg/ml (mean +/- SD) following administration of 3 mg/kg terbinafine, while 7 mg/kg and 15 mg/kg dosages resulted in peak plasma concentrations of 0.37 +/- 0.105 and 0.33 +/- 0.054 microg/ml, respectively. The volume of distribution increased with increasing dosages, being 37 +/- 28.5, 40 +/- 28.1, and 52 +/- 18.6 mg/L for 3, 7, and 15 mg/kg doses, respectively. The mean half-life was biphasic with initial terminal half-life (t(1/2)) values of 9.9 +/- 4.5, 17.2 +/- 4.9 and 16.9 +/- 5.4 hrs, for 3, 7, and 15 mg/kg doses, respectively. A rapid first elimination phase was followed by a slower second phase, and final elimination was estimated to be 136 +/- 9.7 and 131 +/- 9.9 hrs, for 7 and 15 mg/kg doses, respectively. Linearity was demonstrated for area under the curve but not for peak plasma concentrations for the three dosages used. Calculations based on pharmacokinetic parameter values indicate that a 15 mg/kg terbinafine q24h dosage regimen would result in steady-state trough plasma concentrations above the minimum inhibitory concentration (0.8-1.6 microg/ ml), and this dosage is recommended as a potential treatment option for aspergillosis in penguins. However, additional research is required to determine both treatment efficacy and safety.

  1. False Suggestion of Malignant Transformation of Benign Bone Tumor by 18F-FDG PET/CT: A Potential Pitfall.

    PubMed

    Chen, Yu-Ren; Kuo, Yu-Cheng; Hsu, Cheng-Nan; Hsieh, Te-Chun; Kao, Chia-Hung

    2016-10-01

    A 68-year-old man underwent serial F-FDG PET/CT scan follow-up for lung cancer. Then 5.5 years after the initial F-FDG PET/CT scan, the presumed benign bone tumor in the left clavicle showed markedly increased FDG uptake during follow-up; in contrast, the Tc-MDP bone scan paradoxically exhibited no apparent interval change since last bone scan 5.5 years earlier. He underwent a CT-guided biopsy, and the pathological diagnosis was benign fibrous histiocytoma. The result was consistent with the lack of progression in Tc-MDP bone scan, whereas the F-FDG PET/CT scan gave a false-positive impression of malignant transformation. PMID:27556801

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

    PubMed

    Verhasselt, V

    2010-07-01

    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

  3. Assessment of adhesion, invasion and cytotoxicity potential of oral Staphylococcus aureus strains.

    PubMed

    Merghni, Abderrahmen; Ben Nejma, Mouna; Helali, Imen; Hentati, Hajer; Bongiovanni, Antonino; Lafont, Frank; Aouni, Mahjoub; Mastouri, Maha

    2015-09-01

    The oral cavity is regarded as a relevant site for Staphylococcus aureus colonization. However, characterization of virulence mechanisms of oral S. aureus remains to be uncovered. In this study, twenty one S. aureus strains isolated from the oral cavity of Tunisian patients were screened for adherence, invasion and cytotoxicity against HeLa cells. In addition, the presence of adhesins (icaA, icaD, can, fnbA and fnbB) and α-hemolysin (hla) genes in each strain was achieved by polymerase chain reaction (PCR). Our finding revealed that oral S. aureus strains were able to adhere and invade epithelial cells, with variable degrees (P < 0.05). Moreover they exhibited either low (23.8%) or moderate (76.2%) cytotoxic effects. In addition 76.2% of strains were icaA and icaD positive and 90.5% harbor both the fnbA and the fnbB gene. While the cna gene was detected in 12 strains (57.2%). Furthermore, the hla gene encoding the α-toxin was found in 52.4% of the isolates. All these virulence factors give to S. aureus the right qualities to become a redoubtable pathogen associated to oral infections.

  4. A novel series of potent and selective PDE5 inhibitors with potential for high and dose-independent oral bioavailability.

    PubMed

    Allerton, Charlotte M N; Barber, Christopher G; Beaumont, Kevin C; Brown, David G; Cole, Susan M; Ellis, David; Lane, Charlotte A L; Maw, Graham N; Mount, Natalie M; Rawson, David J; Robinson, Colin M; Street, Stephen D A; Summerhill, Nicholas W

    2006-06-15

    Sildenafil (5-[2-ethoxy-5-(4-methyl-1-piperazinylsulfonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one), a potent and selective phosphodiesterase type 5 (PDE5) inhibitor, provided the first oral treatment for male erectile dysfunction. The objective of the work reported in this paper was to combine high levels of PDE5 potency and selectivity with high and dose-independent oral bioavailability, to minimize the impact on the C(max) of any interactions with coadministered drugs in the clinic. This goal was achieved through identification of a lower clearance series with a high absorption profile, by replacing the 5'-piperazine sulfonamide in the sildenafil template with a 5'-methyl ketone. This novel series provided compounds with low metabolism in human hepatocytes, excellent caco-2 flux, and the potential for good aqueous solubility. The in vivo oral and iv pharmacokinetic profiles of example compounds confirmed the high oral bioavailability predicted from these in vitro screens. 5-(5-Acetyl-2-butoxy-3-pyridinyl)-3-ethyl-2-(1-ethyl-3-azetidinyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (2) was selected for progression into the clinic. PMID:16759100

  5. [Criteria for assessing the functional state of the oral mucosa following the combined treatment of malignant tumors of the maxillofacial area].

    PubMed

    Korchak, V V; Volozhin, A I; Zandelov, V L

    1990-01-01

    Polarography and thermometry were employed in examination of the buccal mucosa in 62 patients after combined treatment and primary plasty for malignant tumors of the maxillofacial area. Measurements of pO2 and buccal mucosa temperature were found to yield objective data on the function of the accepting bed in restoration surgery for postoperative defects and to be helpful for the prediction of local complications. Preoperative irradiation according to intensive concentrated scheme induces less marked changes in the mucosa, this being of prophylactic value in cases when local complications develop. The possibility of local complications increases when pO2 reduces twofold and lower vs. the initial level before irradiation. PMID:2371729

  6. New 1-C-(5-thio-D-xylopyranosyl) derivatives as potential orally active venous antithrombotics.

    PubMed

    Mignon, Laurent; Goichot, Christophe; Ratel, Philippe; Cagnin, Gérald; Baudry, Michel; Praly, Jean-Pierre; Boubia, Benaïssa; Barberousse, Véronique

    2003-06-16

    In the search for new orally active antithrombotic drugs that are metabolically stable, we explored the synthesis of 1-C-(5-thio-D-xylosyl) derivatives, examining radical and nucleophilic methods. Thus synthesized were aryl, benzyl, alkylcarboxymethylenyl, arylsulfonylmethylenyl and alkylaminocarboxymethylenyl C-linked analogues of 5-thio-D-xylopyranosides. PMID:12791280

  7. Oral cavity as a potential source of gastric reinfection by Helicobacter pylori.

    PubMed

    Karczewska, Elzbieta; Konturek, Joanna E; Konturek, Peter C; Cześnikiewicz, Marta; Sito, Edward; Bielański, Władysław; Kwiecień, Nina; Obtułowicz, Wojciech; Ziemniak, Witold; Majka, Jolanta; Hahn, Eckhart G; Konturek, Stanislaw J

    2002-05-01

    Helicobacter pylori (Hp) is a common pathogen colonizing the a gastric mucosa, but some reports indicated that it may also be found in the oral cavity, which could serve as a reservoir of the bacteria and a source of gastric reinfection. Accordingly, we aimed to study whether the oral cavity, particularly gingival pockets, are colonized by Hp and whether it could be the source of gastric reinfection. We studied 329 patients with dyspeptic symptoms (257 with chronic gastritis, 15 with gastric ulcer, and 57 with duodenal ulcer). The [13C]urea breath test (UBT), gastroscopy, and Hp culture from gastric biopsies were carried out, and material was collected from the oral cavity (gingival pocket) for bacteriological culture and genomic DNA studies. The serum was obtained for anti-Hp IgG and anti-CagA assays and saliva for anti-Hp IgA determination using the ELISA technique. Bacteria in material from gingival pockets and biopsies from the corpus and antrum of stomach of 30 DU patients before and after Hp eradication were also examined by PCR technique, using primers specific for 16S rRNA. All Hp-positive patients (276) were subjected to one week of triple therapy (omeprazole 2 x 20 mg twice a day, clarithromycin 2 x 500 mg twice a day, and metronidazole 2 x 500 mg twice a day). The measurements described above were then repeated at four weeks and six months. Bacteriological culture showed the presence of Hp in the material from oral cavity in about 50% of patients, whereas UBT, used as a gold standard, revealed gastric Hp infection in about 84% of these patients. The eradication was successful in the majority of patients (87%), but about 13% of them were still Hp positive after four weeks and about 21% after six months. Four weeks after Hp therapy, Hp was found in culture from oral samples in 23% (P < 0.05 vs initial) and after six months in 35.1%. The IgA levels recorded in saliva were in a close agreement with UBT results. Hp DNA assessed by PCR in 30 DUs before

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

    PubMed

    Brondani, Mario Augusto

    2010-12-01

    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

  9. Pleural malignancies.

    PubMed

    Vargas, F S; Teixeira, L R

    1996-07-01

    Carcinoma of the lung, metastatic breast carcinoma, and lymphoma are responsible for approximately 75% of all malignant pleural effusions. The presence of malignant cells in the pleural fluid or in the parietal pleura confirms the diagnosis. Recently, several authors have proposed the combination of morphometric procedures and quantitative analysis of nucleolar organizer regions stained by silver nitrate. Videothoracoscopy is recommended for patients suspected of having a malignant pleural effusion in whom the diagnosis is not established after two cytologic studies of the fluid and one needle biopsy. The standard treatment is the intrapleural instillation of a chemical agent to produce a pleurodesis. The recommended sclerosant is talc, a tetracycline derivative, or Corynebacterium parvum where it is available. When a patient is not an ideal candidate for chemical pleurodesis, the options include symptomatic treatment, serial thoracentesis, implantation of a pleuroperitoneal shunt, and pleurectomy. PMID:9363162

  10. An epidermotropic canine papillomavirus with malignant potential contains an E5 gene and establishes a unique genus.

    PubMed

    Yuan, Hang; Ghim, Shinje; Newsome, Joe; Apolinario, Tania; Olcese, Vanessa; Martin, Mary; Delius, Hajo; Felsburg, Peter; Jenson, Bennett; Schlegel, Richard

    2007-03-01

    A novel canine papillomavirus, CfPV-2, was cloned from a footpad lesion of a golden retriever. Unlike the known canine oral papillomavirus (COPV), which has a double-stranded DNA genome size of 8607 bps, the genome of CfPV-2 is 8101 bps. Some of this size difference is due to an abbreviated early-late region (ELR), which is 1200 bps shorter than that of COPV. However, CfPV-2 has other differences from COPV, including the presence of an E5 ORF between the E2 gene and the ELR and an enlarged E4 ORF (one of the largest PV E4 open reading frames). The genome of CfPV-2 shares low homology with all the other papillomaviruses and, even in the most highly conserved ORF of L1, the nucleotide sequence shares only 57% homology with COPV. Due to this highly divergent DNA sequence, CfPV-2 establishes a new PV genus, with its closest phylogenetic relatives being amongst the Xi and Gamma genuses. CfPV-2 also has unique biological features; it induces papillomas on footpads and interdigital regions which, if infection is persistent, can progress to highly metastatic squamous cell carcinoma. CfPV-2 does not induce oral papillomas in immunocompetent animals and antibodies generated against COPV and CfPV-2 are type-specific. The availability of a new canine papillomavirus with differing genetic and biological properties now makes it possible to study type-specific host immune responses, tissue tropism and the comparative analysis of viral gene functions in the dog. PMID:17034826

  11. Probiotics in oral health--a review.

    PubMed

    Rao, Yadav; Lingamneni, Benhur; Reddy, Deepika

    2012-01-01

    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.

  12. Depth sensitive oblique polarized reflectance spectroscopy of oral epithelial tissue

    NASA Astrophysics Data System (ADS)

    Jimenez, Maria K.; Lam, Sylvia; Poh, Catherine; Sokolov, Konstantin

    2014-05-01

    Identifying depth-dependent alterations associated with epithelial cancerous lesions can be challenging in the oral cavity where variable epithelial thicknesses and troublesome keratin growths are prominent. Spectroscopic methods with enhanced depth resolution would immensely aid in isolating optical properties associated with malignant transformation. Combining multiple beveled fibers, oblique collection geometry, and polarization gating, oblique polarized reflectance spectroscopy (OPRS) achieves depth sensitive detection. We report promising results from a clinical trial of patients with oral lesions suspected of dysplasia or carcinoma demonstrating the potential of OPRS for the analysis of morphological and architectural changes in the context of multilayer, epithelial oral tissue.

  13. Oral lichen planus: a literature review and update.

    PubMed

    Alrashdan, Mohammad S; Cirillo, Nicola; McCullough, Michael

    2016-10-01

    Lichen planus (LP) is a common chronic inflammatory condition that can affect skin and mucous membranes, including the oral mucosa. Because of the anatomic, physiologic and functional peculiarities of the oral cavity, the oral variant of LP (OLP) requires specific evaluations in terms of diagnosis and management. In this comprehensive review, we discuss the current developments in the understanding of the etiopathogenesis, clinical-pathologic presentation, and treatment of OLP, and provide follow-up recommendations informed by recent data on the malignant potential of the disease as well as health economics evaluations. PMID:27349424

  14. MicroRNAs-mRNAs Expression Profile and Their Potential Role in Malignant Transformation of Human Bronchial Epithelial Cells Induced by Cadmium

    PubMed Central

    Liu, Qun; Zheng, Chanjiao; Shen, Huanyu; Zhou, Zhiheng; Lei, Yixiong

    2015-01-01

    Background. Our study was designed to elucidate whether there were miRNA and mRNA aberrantly expression profiles and potential role in malignant transformation of 16HBE induced by Cd. Methods. mRNA and miRNA expression profiles were determined in 35th Cd-induced 16HBE and untreated 16HBE by microarray. A series of bioinformatics analyses such as predicting targets, GO, KEGG were performed to find DEGs, coexpressing networks between miRNAs and mRNAs and its functions. Results. 498 DEGs were found. 8 Cd-responsive novel miRNAs predicted previously were identified, and 5 of them were downregulated. 214 target genes were predicted for the Cd-responsive miRNAs, many of which appeared to regulate gene networks. Target gene CCM2 was showed reciprocal effect by miRNAs. According to the combination analysis, hsa-miR-27b-3p regulated most of the mRNAs, especially upregulated expression genes. The differentially expressed miRNAs are involved in the biological processes and channels, and these GO and KEGG enrichment analyses result were significantly enriched in the Cd-responsive. Discussion. These results provided a tight link for the miRNA-mRNA integrated network and implied the role of novel miRNAs in malignant transformation of 16HBE induced by Cadmium. It is better to understand the novel molecular mechanism of cadmium-induced tumorigenesis. PMID:26504844

  15. 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

    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.

    2013-01-01

    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

  16. Ras-Driven Transcriptome Analysis Identifies Aurora Kinase A as a Potential Malignant Peripheral Nerve Sheath Tumor Therapeutic Target

    PubMed Central

    Patel, Ami V.; Eaves, David; Jessen, Walter J.; Rizvi, Tilat A.; Ecsedy, Jeffrey A.; Qian, Mark G.; Aronow, Bruce J.; Perentesis, John P.; Serra, Eduard; Cripe, Timothy P.; Miller, Shyra J.; Ratner, Nancy

    2013-01-01

    Purpose Patients with Neurofibromatosis Type 1 (NF1) develop malignant peripheral nerve sheath tumors (MPNST) which are often inoperable and do not respond well to current chemotherapies or radiation. The goal of this study was to utilize comprehensive gene expression analysis to identify novel therapeutic targets. Experimental Design Nerve Schwann cells and/or their precursors are the tumorigenic cell types in MPNST due to the loss of the NF1 gene, which encodes the RasGAP protein neurofibromin. Therefore, we created a transgenic mouse model, CNP-HRas12V, expressing constitutively-active HRas in Schwann cells and defined a Ras-induced gene expression signature to drive a Bayesian factor regression model analysis of differentially expressed genes in mouse and human neurofibromas and MPNSTs. We tested functional significance of Aurora kinase over-expression in MPNST in vitro and in vivo using Aurora kinase shRNAs and compounds that inhibit Aurora kinase. Results We identified 2000 genes with probability of linkage to nerve Ras signaling of which 339 were significantly differentially expressed in mouse and human NF1-related tumor samples relative to normal nerves, including Aurora kinase A (AURKA). AURKA was dramatically over-expressed and genomically amplified in MPNSTs but not neurofibromas. Aurora kinase shRNAs and Aurora kinase inhibitors blocked MPNST cell growth in vitro. Furthermore, an AURKA selective inhibitor, MLN8237, stabilized tumor volume and significantly increased survival of mice with MPNST xenografts. Conclusion Integrative cross-species transcriptome analyses combined with preclinical testing has provided an effective method for identifying candidates for molecular-targeted therapeutics. Blocking Aurora kinases may be a viable treatment platform for MPNST. PMID:22811580

  17. Hematologic malignancies

    SciTech Connect

    Hoogstraten, B.

    1986-01-01

    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.

  18. Malignant hyperthermia.

    PubMed

    Taiclet, L

    1985-01-01

    Despite numerous reviews and clinical reports, much remains to be learned about the cause, treatment, and prevention of malignant hyperthermia.Among the most worrisome concerns of the clinician administering anesthesia is the malignant hyperthermia crisis. When it arises, it is always frightening-and sometimes fatal. Usually occurring very suddenly and without warning, malignant hyperthermia is considered to be a hypercatabolic crisis; the condition is known to affect humans and certain breeds of pigs. The exact triggering mechanisms of malignant hyperthermia (MH) in humans are not known, but a crisis can be initiated by volatile general anesthetics, neuromuscular blocking agents, and amide local anesthetics. Although a history of an MH crisis is a diagnostic aid, previous uneventful exposure to anesthesia does not guarantee the safety of the patient in subsequent anesthetic procedures.(1) For these reasons, it is important for the anesthesiologist to be aware of the initial signs of MH and to be prepared to provide immediate treatment to reverse such a crisis. PMID:3865561

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

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

    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.

  20. Potential for use of retinoic acid as an oral vaccine adjuvant

    PubMed Central

    Mwanza-Lisulo, Mpala; Kelly, Paul

    2015-01-01

    Despite the heavy burden of diarrhoeal disease across much of the tropical world, only two diarrhoea-causing pathogens, cholera and rotavirus, are the target of commercially available vaccines. Oral vaccines are generally less immunogenic than the best parenteral vaccines, but the reasons for this are still debated. Over the past decade, several lines of evidence from work in experimental animals have suggested that all-trans retinoic acid (ATRA), a form of vitamin A which is highly transcriptionally active, can alter the homing receptor expression of T lymphocytes. Increased expression of α4β7 integrin and the chemokine receptor CCR9 following exposure to ATRA can be used to redirect T cells to the gut. Early work in human volunteers suggests that oral ATRA administration 1 h prior to dosing with oral typhoid vaccine can augment secretion of specific IgA against vaccine-derived lipopolysaccharide into gut secretions. In this review, we set out the rationale for using ATRA in this way and assess its likely applicability to vaccination programmes for protection of children in low-income countries from the considerable mortality caused by diarrhoeal disease. Comparison of recent work in experimental animals, non-human primates and men suggests that a more detailed understanding of ATRA dosage and kinetics will be important to taking forward translational work into human vaccinology. PMID:25964457

  1. Aerobic bacterial oral flora of garter snakes: development of normal flora and pathogenic potential for snakes and humans.

    PubMed Central

    Goldstein, E J; Agyare, E O; Vagvolgyi, A E; Halpern, M

    1981-01-01

    Garter snakes that are used for scientific laboratory studies or kept as exotic pets often become ill and die early in captivity. They may also act as reservoirs of potential human pathogens or transmit infection to man. A total of 126 strains of aerobic and facultative bacteria, most potential human and snake pathogens, were isolated from 82 garter snake oropharyngeal cultures. Coagulase-negative Staphylococcus species were the most common species isolated. Acinetobacter calcoaceticus var. anitratus, Hafnia alvei, Arizona hinshawii, Salmonella species, Shigella species, Klebsiella oxytoca, and Pseudomonas aeruginosa were among the potential pathogens isolated. The spectrum of bacteria with potential for causing oral and pulmonary infections in garter snakes is greater than has been previously appreciated. Garter snakes should also be considered reservoirs of human pathogens, and appropriate precautions should be taken by laboratory personnel and pet owners. PMID:7240404

  2. Human papillomavirus infections and oral tumors.

    PubMed

    Syrjänen, Stina

    2003-08-01

    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.

  3. Soluble CD14 and toll-like receptor-2 are potential salivary biomarkers for oral lichen planus and burning mouth syndrome.

    PubMed

    Srinivasan, Mythily; Kodumudi, Krithika N; Zunt, Susan L

    2008-01-01

    Oral lichen planus (OLP) and burning mouth syndrome (BMS) are chronic conditions affecting the oral mucosa characterized by pain and burning sensation. Saliva plays a significant role in the maintenance of physical and functional integrity of normal oral mucosa. Identification of potential "salivary biomarkers" for early diagnosis and/or monitoring of human diseases is being explored. We investigated the soluble forms of innate immune associated proteins CD14 and toll-like receptor-2 in unstimulated whole saliva (UWS) as potential biomarkers for OLP and BMS. Our results suggest that the levels of sCD14 and sTLR-2 in UWS were upregulated in OLP and BMS respectively. In addition, oral epithelial cells in the saliva of patients with OLP and BMS exhibited elevated levels of CD14 mRNA and decreased levels of TLR-2 mRNA. Interestingly, presence of co-existent oral candidiasis nullified these changes.

  4. Investigations on the potential of a low power diode pumped Er:YAG laser system for oral surgery

    NASA Astrophysics Data System (ADS)

    Stock, Karl; Wurm, Holger; Hausladen, Florian; Wagner, Sophia; Hibst, Raimund

    2015-02-01

    Flash lamp pumped Er:YAG-lasers are used in clinical practice for dental applications successfully. As an alternative, several diode pumped Er:YAG laser systems (Pantec Engineering AG) become available, with mean laser power of 2W, 15W, and 30W. The aim of the presented study is to investigate the potential of the 2W Er:YAG laser system for oral surgery. At first an appropriate experimental set-up was realized with a beam delivery and both, a focusing unit for non-contact tissue cutting and a fiber tip for tissue cutting in contact mode. In order to produce reproducible cuts, the samples (porcine gingiva) were moved by a computer controlled translation stage. On the fresh samples cutting depth and quality were determined by light microscopy. Afterwards histological sections were prepared and microscopically analyzed regarding cutting depth and thermal damage zone. The experiments show that low laser power ≤ 2W is sufficient to perform efficient oral soft tissue cutting with cut depth up to 2mm (sample movement 2mm/s). The width of the thermal damage zone can be controlled by the irradiation parameters within a range of about 50μm to 110μm. In general, thermal injury is more pronounced using fiber tips in contact mode compared to the focused laser beam. In conclusion the results reveal that even the low power diode pumped Er:YAG laser is an appropriate tool for oral surgery.

  5. Poly-α,β-Polyasparthydrazide-Based Nanogels for Potential Oral Delivery of Paclitaxel: In Vitro and In Vivo Properties.

    PubMed

    Guo, Jingwen; Ma, Mingxin; Chang, Di; Zhang, Qiang; Zhang, Chen; Yue, Yang; Liu, Jia; Wang, Siling; Jiang, Tongying

    2015-12-01

    A family of nanogel drug carriers has been designed to enhance the oral absorption of paclitaxel (PTX). The PAHy-based nanogels were prepared by the interpenetration of poly-α,β-polyasparthydrazide (PAHy) chains and dicarboxyl-poly (ethylene glycol) (CPEG), forming a smart chain network. The PAHy-based nanogels were characterized by Fourier Transform Infrared Spectroscopy (FT-IR), dynamic light scattering (DLS), X-ray diffraction (XRD) and high performance liquid chromatography (HPLC). The adhesion and retention properties of fluorescein isothiocyanate (FITC)-nanogels in vivo were investigated using an in vivo imaging system and confocal laser scanning microscopy (CLSM). The smart nanogels had a particle size of -200 nm, increased the degree and rate of release, and spent over 12 h in the gastrointestinal tract. They also produced excellent adhesion, permeability and retention (APR) effects and increased oral absorption, confirming their use as potential sustained-release carriers for the oral delivery of the hydrophobic anticancer agent PTX. PMID:26510316

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

    PubMed Central

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

    2011-01-01

    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 α-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. PMID:21822379

  7. Molecular markers in oral lichen planus: A systematic review

    PubMed Central

    Sagari, Shitalkumar; Sanadhya, Sudhanshu; Doddamani, Mallikarjun; Rajput, Rajan

    2016-01-01

    Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that is usually detected in 0.5–2.2% of the human population. Among these, only 0.5–2.9% of the lesions progress to carcinoma. However, there are no prognostic markers available presently to recognize the increased risk in malignant transformation of the lesions. Selected markers for cell proliferation, adhesion, apoptosis and lymphocytic infiltration were analyzed by immunohistochemistry in addition to static cytometry for DNA content. The concept linking OLP and oral squamous cell carcinoma states that chronic inflammation results in crucial DNA damage, which further progresses to development of carcinoma. Even though in the past decade, enormous information has been accumulated on malignant potential of OLP, its transformation still remains unclear. Hence, the purpose of this article was to review cellular and molecular markers to understand the pathogenesis of OLP and its progression toward malignancy. PMID:27194873

  8. Applications of OralCDx ® methodology in the diagnosis of oral leukoplakia

    PubMed Central

    García-Carnicero, Tamara; Gándara-Vila, Pilar; Couso-Folgueiras, Elena; Pérez-Sayáns, Mario; Gándara-Vila, Rafael; García-García, Abel; Gándara-Rey, José-Manuel

    2012-01-01

    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. PMID:21743402

  9. Lipid-based oral delivery systems for skin deposition of a potential chemopreventive DIM derivative: characterization and evaluation.

    PubMed

    Boakye, Cedar H A; Patel, Ketan; Patel, Apurva R; Faria, Henrique A M; Zucolotto, Valtencir; Safe, Stephen; Singh, Mandip

    2016-10-01

    The objective of this study was to explore the oral route as a viable potential for the skin deposition of a novel diindolylmethane derivative (DIM-D) for chemoprevention activity. Various lipid-based oral delivery systems were optimized and compared for enhancing DIM-D's oral bioavailability and skin deposition. Preformulation studies were performed to evaluate the log P and solubility of DIM-D. Microsomal metabolism, P-glycoprotein efflux, and caco-2 monolayer permeability of DIM-D were determined. Comparative evaluation of the oral absorption and skin deposition of DIM-D-loaded various lipid-based formulations was performed in rats. DIM-D showed pH-dependent solubility and a high log P value. It was not a strong substrate of microsomal degradation and P-glycoprotein. SMEDDs comprised of medium chain triglycerides, monoglycerides, and kolliphor-HS15 (36.70 ± 0.42 nm). SNEDDs comprised of long chain triglycerides, cremophor RH40, labrasol, and TPGS (84.00 ± 14.14 nm). Nanostructured lipid carriers (NLC) consisted of compritol, miglyol, and surfactants (116.50 ± 2.12 nm). The blank formulations all showed >70 % cell viability in caco-2 cells. Differential Scanning Calorimetry confirmed the amorphization of DIM-D within the lipid matrices while Atomic Force Microscopy showed particle size distribution similar to the dynamic light scattering data. DIM-D also showed reduced permeation across caco-2 monolayer that was enhanced (p < 0.05) by SNEDDs in comparison to SMEDDs and NLC. Fabsolute for DIM-D SNEDDs, SMEDDs, and NLC was 0.14, 0.04, and 0.007, respectively. SNEDDs caused 53.90, 11.32, and 15.08-fold more skin deposition of DIM-D than the free drug, SMEDDs, and NLC, respectively, at 2 h following oral administration and shows a viable potential for use in skin cancer chemoprevention. Graphical Abstract ᅟ. PMID:27405772

  10. Lipid-based oral delivery systems for skin deposition of a potential chemopreventive DIM derivative: characterization and evaluation.

    PubMed

    Boakye, Cedar H A; Patel, Ketan; Patel, Apurva R; Faria, Henrique A M; Zucolotto, Valtencir; Safe, Stephen; Singh, Mandip

    2016-10-01

    The objective of this study was to explore the oral route as a viable potential for the skin deposition of a novel diindolylmethane derivative (DIM-D) for chemoprevention activity. Various lipid-based oral delivery systems were optimized and compared for enhancing DIM-D's oral bioavailability and skin deposition. Preformulation studies were performed to evaluate the log P and solubility of DIM-D. Microsomal metabolism, P-glycoprotein efflux, and caco-2 monolayer permeability of DIM-D were determined. Comparative evaluation of the oral absorption and skin deposition of DIM-D-loaded various lipid-based formulations was performed in rats. DIM-D showed pH-dependent solubility and a high log P value. It was not a strong substrate of microsomal degradation and P-glycoprotein. SMEDDs comprised of medium chain triglycerides, monoglycerides, and kolliphor-HS15 (36.70 ± 0.42 nm). SNEDDs comprised of long chain triglycerides, cremophor RH40, labrasol, and TPGS (84.00 ± 14.14 nm). Nanostructured lipid carriers (NLC) consisted of compritol, miglyol, and surfactants (116.50 ± 2.12 nm). The blank formulations all showed >70 % cell viability in caco-2 cells. Differential Scanning Calorimetry confirmed the amorphization of DIM-D within the lipid matrices while Atomic Force Microscopy showed particle size distribution similar to the dynamic light scattering data. DIM-D also showed reduced permeation across caco-2 monolayer that was enhanced (p < 0.05) by SNEDDs in comparison to SMEDDs and NLC. Fabsolute for DIM-D SNEDDs, SMEDDs, and NLC was 0.14, 0.04, and 0.007, respectively. SNEDDs caused 53.90, 11.32, and 15.08-fold more skin deposition of DIM-D than the free drug, SMEDDs, and NLC, respectively, at 2 h following oral administration and shows a viable potential for use in skin cancer chemoprevention. Graphical Abstract ᅟ.

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

    PubMed Central

    Palombo, Enzo A.

    2011-01-01

    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. PMID:19596745

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

    PubMed

    Palombo, Enzo A

    2011-01-01

    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.

  13. Readily restoring freeze-dried probilosomes as potential nanocarriers for enhancing oral delivery of cyclosporine A.

    PubMed

    Guan, Peipei; Lu, Yi; Qi, Jianping; Wu, Wei

    2016-08-01

    Formulating vesicular nanocarriers into dried precursors so as to overcome the drawbacks associated with liquid formulations is challengeable due to low efficiency of restoration. In this study, bilosomes interiorly thickened with gelatin (G-BLs) was evaluated for the ability to withstand freeze-drying stress and enhanced oral bioavailability of a model drug, cyclosporine A (CyA). The restoration efficiency of freeze-dried pro-G-BLs is investigated by comparing the particle size distribution, entrapment efficiency and morphology of the bilosomes before and after freeze-drying. Particle size and polydispersity index (PI) of pro-G-BLs after restoration was similar to that before freeze-drying, whereas freeze-dried bilosomes without gelatin thickening (pro-BLs) show irreversible damage and aggregation along with significantly increased particle size and PI after restoration. Entrapment efficiency of pro-G-BLs remains as high as 83.7%, in sharp contrast with 66.7% for pro-BLs. Pharmacokinetics in beagle dogs show improved absorption of CyA in pro-G-BLs as compared to pro-BLs, G-BLs and microemulsion-based Sandimmun Neoral(®). The relative oral bioavailability of CyA-loaded pro-G-BLs, pro-BLs and G-BLs was 165.2%, 123.5% and 130.1%, respectively, with Neoral(®) as the reference. It is concluded that interior thickening with gelatin significantly enhanced the stability against freeze-drying stress, which as a result improves the restoring efficiency and oral bioavailability. PMID:27085046

  14. Oral manifestations of hepatitis C virus infection

    PubMed Central

    Carrozzo, Marco; Scally, Kara

    2014-01-01

    Extrahepatic manifestations (EHMs) of hepatitis C virus (HCV) infection can affect a variety of organ systems with significant morbidity and mortality. Some of the most frequently reported EHM of HCV infection, involve the oral region predominantly or exclusively. Oral lichen planus (OLP) is a chronic inflammatory condition that is potentially malignant and represents cell-mediated reaction to a variety of extrinsic antigens, altered self-antigens, or super antigens. Robust epidemiological evidence support the link between OLP and HCV. As the virus may replicate in the oral mucosa and attract HCV-specific T lymphocytes, HCV may be implicated in OLP pathogenesis. Sjögren syndrome (SjS) is an autoimmune exocrinopathy, characterized by dryness of the mouth and eyes and a multitude of other systemic signs and symptoms. SjS patients have also an increased risk of non-Hodgkin lymphoma. Patients with chronic hepatitis C do frequently have histological signs of Sjögren-like sialadenitis with mild or even absent clinical symptoms. However, it is still unclear if HCV may cause a disease mimicking SjS or it is directly responsible for the development of SjS in a specific subset of patients. Oral squamous cell carcinoma is the most common oral malignant tumour and at least in some part of the world could be linked to HCV. PMID:24976694

  15. Oral manifestations of hepatitis C virus infection.

    PubMed

    Carrozzo, Marco; Scally, Kara

    2014-06-28

    Extrahepatic manifestations (EHMs) of hepatitis C virus (HCV) infection can affect a variety of organ systems with significant morbidity and mortality. Some of the most frequently reported EHM of HCV infection, involve the oral region predominantly or exclusively. Oral lichen planus (OLP) is a chronic inflammatory condition that is potentially malignant and represents cell-mediated reaction to a variety of extrinsic antigens, altered self-antigens, or super antigens. Robust epidemiological evidence support the link between OLP and HCV. As the virus may replicate in the oral mucosa and attract HCV-specific T lymphocytes, HCV may be implicated in OLP pathogenesis. Sjögren syndrome (SjS) is an autoimmune exocrinopathy, characterized by dryness of the mouth and eyes and a multitude of other systemic signs and symptoms. SjS patients have also an increased risk of non-Hodgkin lymphoma. Patients with chronic hepatitis C do frequently have histological signs of Sjögren-like sialadenitis with mild or even absent clinical symptoms. However, it is still unclear if HCV may cause a disease mimicking SjS or it is directly responsible for the development of SjS in a specific subset of patients. Oral squamous cell carcinoma is the most common oral malignant tumour and at least in some part of the world could be linked to HCV. PMID:24976694

  16. Computer aided morphometric analysis of oral leukoplakia and oral squamous cell carcinoma.

    PubMed

    Gupta, K; Gupta, J; Miglani, R

    2016-01-01

    We compared the changes in the cells in the basal layer of normal mucosa, oral leukoplakia with dysplasia and different grades of oral squamous cell carcinoma (OSCC) using computer aided image analysis of tissue sections. We investigated three morphometric parameters: nuclear area (NA), cell area (CA) and their ratio (NA:CA). NA and NA:CA ratio showed a statistically significant increase from dysplasia to increasing grades of OSCC. Nuclear size was useful for differentiating normal tissue, potentially malignant leukoplakia and OSCC. PMID:26983454

  17. Do oral bacteria alter the regenerative potential of stem cells? A concise review.

    PubMed

    Chatzivasileiou, Kyriaki; Kriebel, Katja; Steinhoff, Gustav; Kreikemeyer, Bernd; Lang, Hermann

    2015-09-01

    Mesenchymal stem cells (MSCs) are widely recognized as critical players in tissue regeneration. New insights into stem cell biology provide evidence that MSCs may also contribute to host defence and inflammation. In case of tissue injury or inflammatory diseases, e.g. periodontitis, stem cells are mobilized towards the site of damage, thus coming in close proximity to bacteria and bacterial components. Specifically, in the oral cavity, complex ecosystems of commensal bacteria live in a mutually beneficial state with the host. However, the formation of polymicrobial biofilm communities with pathogenic properties may trigger an inadequate host inflammatory-immune response, leading to the disruption of tissue homoeostasis and development of disease. Because of their unique characteristics, MSCs are suggested as crucial regulators of tissue regeneration even under such harsh environmental conditions. The heterogeneous effects of bacteria on MSCs across studies imply the complexity underlying the interactions between stem cells and bacteria. Hence, a better understanding of stem cell behaviour at sites of inflammation appears to be a key strategy in developing new approaches for in situ tissue regeneration. Here, we review the literature on the effects of oral bacteria on cell proliferation, differentiation capacity and immunomodulation of dental-derived MSCs.

  18. Contaminated tooth brushes–potential threat to oral and general health

    PubMed Central

    Naik, Rashmi; Ahmed Mujib, B. R.; Telagi, Neethu; Anil, B. S.; Spoorthi, B. R.

    2015-01-01

    Background: Tooth brushing is most common method of maintaining oral hygiene. In removing plaque and other soft debris from the teeth, tooth brushes become contaminated with bacteria, blood, saliva and oral debris. These contaminated tooth brushes can be a source of infection. Aims and objectives: The aim of the present study was to evaluate the presence of microorganisms in the tooth brushes and to investigate the effect of disinfectants such as chlorhexidine gluconate, sodium hypochlorite and water to decontaminate them. Materials and Methods: Twenty-one children were asked to brush their teeth for 5 days with a tooth brush. The tooth brushes were put in Robertson's Cooked Meat broth and were observed for growth of Streptococcal microorganisms. These tooth brushes were then placed in disinfectants such as 0.2% chlorhexidine gluconate (Group I), 1% sodium hypochlorite (Group II) and water (Group III) for 24 hrs and then cultured again. Reduction of growth of microorganisms was seen in Group I, Group II and remnants of growth seen in Group III. Conclusion: We conclude that the use of disinfectant for a tooth brush is a must for every individual at least at regular intervals. PMID:26288790

  19. Attenuated Salmonella typhimurium SV4089 as a potential carrier of oral DNA vaccine in chickens.

    PubMed

    Jazayeri, Seyed Davoud; Ideris, Aini; Zakaria, Zunita; Omar, Abdul Rahman

    2012-01-01

    Attenuated Salmonella has been used as a carrier for DNA vaccine. However, in vitro and in vivo studies on the bacteria following transfection of plasmid DNA were poorly studied. In this paper, eukaryotic expression plasmids encoding avian influenza virus (AIV) subtype H5N1 genes, pcDNA3.1/HA, NA, and NP, were transfected into an attenuated Salmonella enteric typhimurium SV4089. In vitro stability of the transfected plasmids into Salmonella were over 90% after 100 generations. The attenuated Salmonella were able to invade MCF-7 (1.2%) and MCF-10A (0.5%) human breast cancer cells. Newly hatched specific-pathogen-free (SPF) chicks were inoculated once by oral gavage with 10(9) colony-forming unit (CFU) of the attenuated Salmonella. No abnormal clinical signs or deaths were recorded after inoculation. Viable bacteria were detected 3 days after inoculation by plating from spleen, liver, and cecum. Fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR) were carried out for confirmation. Salmonella was not detected in blood cultures although serum antibody immune responses to Salmonella O antiserum group D1 factor 1, 9, and 12 antigens were observed in all the inoculated chickens after 7 days up to 35 days. Our results showed that live attenuated S. typhimurium SV4089 harboring pcDNA3.1/HA, NA, and NP may provide a unique alternative as a carrier for DNA oral vaccine in chickens.

  20. Potential of Diffusion-Weighted Imaging in the Characterization of Malignant, Benign, and Healthy Breast Tissues and Molecular Subtypes of Breast Cancer

    PubMed Central

    Sharma, Uma; Sah, Rani G.; Agarwal, Khushbu; Parshad, Rajinder; Seenu, Vurthaluru; Mathur, Sandeep R.; Hari, Smriti; Jagannathan, Naranamangalam R.

    2016-01-01

    The role of apparent diffusion coefficient (ADC) in the diagnosis of breast cancer and its association with molecular biomarkers was investigated in 259 patients with breast cancer, 67 with benign pathology, and 54 healthy volunteers using diffusion-weighted imaging (DWI) at 1.5 T. In 59 breast cancer patients, dynamic contrast-enhanced MRI (DCEMRI) was also acquired. Mean ADC of malignant lesions was significantly lower (1.02 ± 0.17 × 10−3 mm2/s) compared to benign (1.57 ± 0.26 × 10−3 mm2/s) and healthy (1.78 ± 0.13 × 10−3 mm2/s) breast tissues. A cutoff ADC value of 1.23 × 10−3 mm2/s (sensitivity 92.5%; specificity 91.1%; area under the curve 0.96) to differentiate malignant from benign diseases was arrived by receiver operating curve analysis. In 10/59 breast cancer patients, indeterminate DCE curve was seen, while their ADC value was indicative of malignancy, implying the potential of the addition of DWI in increasing the specificity of DCEMRI data. Further, the association of ADC with tumor volume, stage, hormonal receptors [estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor (HER2)], and menopausal status was investigated. A significant difference was seen in tumor volume between breast cancer patients of stages IIA and IIIA, IIB and IIIA, and IIB and III (B + C), respectively (P < 0.05). Patients with early breast cancer (n = 52) had significantly lower ADC and tumor volume than those with locally advanced breast cancer (n = 207). No association was found in ADC and tumor volume with the menopausal status. Breast cancers with ER−, PR−, and triple-negative (TN) status showed a significantly larger tumor volume compared to ER+, PR+, and non-triple-negative (nTN) cancers, respectively. Also, TN tumors showed a significantly higher ADC compared to ER+, PR+, and nTN cancers. Patients with ER− and TN cancers were younger than those with ER+ and nTN cancers

  1. Can MMP-9 be a Prognosticator Marker for Oral Squamous Cell Carcinoma?

    PubMed Central

    Basu, Shiva Kumar; Kumar, Manish

    2016-01-01

    Introduction Invasion and metastasis of malignant tumours severely endanger the life of cancer patients. Squamous cell carcinoma is one of the commonly found malignancies in the oral cavity and its survival rate has not improved from past few decades. Since an important risk factor for oral squamous cell carcinoma is the presence of epithelial dysplasia, it is necessary to check the presence of a prognosticator marker in both of them. As matrix metalloproteinase’s (MMP’s) are involved in degradation of type IV collagen, which are one of the important components of extracellular matrix components which play a relevant role in several steps of tumour progression such as invasion and metastasis. We have studied MMP-9 expression to evaluate its prognostic potential in oral cancers as well as oral epithelial dysplasia along with tissues of normal oral epithelium. Materials and Methods The expression was examined using immunohistochemistry procedure with MMP-9 in 100 samples including cases of epithelium from normal oral mucosa, oral dysplastic lesions and oral squamous cell carcinoma. One set of formalin fixed, paraffin embedded sections of the three categories were stained by haematoxylin and eosin. The sections were then evaluated under microscope. Data was examined for statistical significance using SPSS 13.0 by Mann-Whitney Test and Kruskal-Wallis Test. Results With MMP-9 gain of expression was noted from Control group to oral squamous cell carcinoma. Cytoplasmic staining was seen with MMP-9. Statistically highly significant differences were seen between oral epithelial dysplasia and oral squamous cell carcinoma and statistically significant differences were found between the control group and the oral squamous cell carcinoma group. Conclusion This study suggested that oral squamous cell carcinoma shows higher MMP-9 expression as compared to oral epithelial dysplasia followed by epithelium from normal oral mucosa. However, no correlation was found among the

  2. Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence

    PubMed Central

    Chaidos, Aristeidis; Caputo, Valentina

    2015-01-01

    Post-translational modifications of the nucleosomal histone proteins orchestrate chromatin organization and gene expression in normal and cancer cells. Among them, the acetylation of N-terminal histone tails represents the fundamental epigenetic mark of open structure chromatin and active gene transcription. The bromodomain and extra-terminal (BET) proteins are epigenetic readers which utilize tandem bromodomains (BRD) modules to recognize and dock themselves on the acetylated lysine tails. The BET proteins act as scaffolds for the recruitment of transcription factors and chromatin organizers required in transcription initiation and elongation. The recent discovery of small molecules capable of blocking their lysine-binding pocket is the first paradigm of successful pharmacological inhibition of epigenetic readers. JQ1 is a prototype benzodiazepine molecule and a specific BET inhibitor with antineoplastic activity both in solid tumours and haematological malignancies. The quinolone I-BET151 and the suitable for clinical development I-BET762 benzodiazepine were introduced in parallel with JQ1 and have also shown potent antitumour activity in preclinical studies. I-BET762 is currently being tested in early phase clinical trials, along with a rapidly growing list of other BET inhibitors. Unlike older epigenetic therapies, the study of BET inhibitors has offered substantial, context-specific, mechanistic insights of their antitumour activity, which will facilitate optimal therapeutic targeting in future. Here, we review the development of this novel class of epigenetic drugs, the biology of BET protein inhibition, the emerging evidence from preclinical work and early phase clinical studies and we discuss their potential role in the treatment of haematological malignancies. PMID:26137204

  3. Epithelial Dysplasia in Oral Cavity

    PubMed Central

    Shirani, Samaneh; Kargahi, Neda; Razavi, Sayed Mohammad; Homayoni, Solmaz

    2014-01-01

    Among oral lesions, we encounter a series of malignant epithelial lesions that go through clinical and histopathologic processes in order to be diagnosed. Identifying these processes along with the etiology knowledge of these lesions is very important in prevention and early treatments. Dysplasia is the step preceding the formation of squamous cell carcinoma in lesions which have the potential to undergo dysplasia. Identification of etiological factors, clinical and histopathologic methods has been the topic of many articles. This article, reviews various articles presenting oral cavity dysplasia, new clinical methods of identifying lesions, and the immunohistochemical research which proposes various markers for providing more precise identification of such lesions. This article also briefly analyzes new treatment methods such as tissue engineering. PMID:25242838

  4. Potential of ordered mesoporous silica for oral delivery of poorly soluble drugs.

    PubMed

    Vialpando, Monica; Martens, Johan A; Van den Mooter, Guy

    2011-08-01

    The use of ordered mesoporous silica is one of the more recent and rapidly developing formulation techniques for enhancing the solubility of poorly water-soluble drugs. Their large surface area and pore volume make ordered mesoporous silica materials excellent candidates for efficient drug loading and rapid release. While this new approach offers many promising advantages, further research is still necessary to elucidate the molecular mechanisms and to improve our scientific insight into the behavior of this system. In this review, the significant developments to date are presented and research challenges highlighted. Aspects of downstream processability are discussed in view of their special bulk powder properties and unique pore architecture. Lastly, perspectives for successful oral dosage form development are presented. PMID:22833866

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

    PubMed Central

    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

    2013-01-01

    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. PMID:21815141

  6. Ascending parabrachio-thalamo-striatal pathways: potential circuits for integration of gustatory and oral motor functions.

    PubMed

    Iwai, H; Kuramoto, E; Yamanaka, A; Sonomura, T; Uemura, M; Goto, T

    2015-05-21

    The medial parabrachial nucleus (MPB) and external part of the medial parabrachial nucleus (MPBE) relay gustatory, oral mechanosensory and other visceral information in the rat brain and reportedly project not only to the parvicellular part of the posteromedial ventral thalamic nucleus (VPMpc) but also to the ventrocaudal part of the intralaminar thalamic nuclei. Generally, the intralaminar thalamic nuclei project topographically to the caudate putamen (CPu); however, it is unclear where the ventrocaudal part of the intralaminar thalamic nuclei projects within the CPu. Thus, we visualized neural pathways from the MPB and MPBE to the CPu via the ventrocaudal part of the intralaminar thalamic nuclei using an anterograde tracer, biotinylated dextran amine, and a retrograde tracer, cholera toxin B subunit. We found that the MPB and MPBE sent a relatively stronger input to the ventrocaudal part of the intralaminar thalamic nuclei such as the oval paracentral thalamic nucleus (OPC), central medial thalamic nucleus (CM) and parafascicular thalamic nucleus (PF) and retroreuniens area (RRe) as compared to the VPMpc. In turn, these thalamic nuclei projected to the ventral part of the CPu with the topographical arrangement as follows: the OPC to the ventrocentral part of the CPu; ventrolateral part of the PF to the ventrolateral part of the CPu; and the caudal part of the CM, ventromedial part of the PF and RRe to the ventromedial part of the CPu. Further, we found that the VPMpc rather projected to the interstitial nucleus of the posterior limb of the anterior commissure than the CPu. The ventral part of the CPu is reported to be involved in jaw movement as well as food and water intake functions. Therefore, these parabrachio-thalamo-striatal pathways that we demonstrated here suggest that gustatory and oral mechanosensory information affects feeding behavior within the ventral part of the CPu.

  7. Treatments of the oral leukoplakia by laser

    NASA Astrophysics Data System (ADS)

    Capocci, M.; Mohsen, M.; Lo Giudice, R.; Del Vecchio, A.; Gaimari, G.; Tribolati, L.; Palaia, G.; Romeo, U.

    2016-03-01

    Oral leukoplakia is catalogued under the group of "potentially malignant disorders". In daily practice, the World Health Organization definition "white patch or plaque that cannot be characterized clinically or histologically as any other disease" is completed by including the observation that it cannot be removed by simple scraping, thereby distinguishing it from pseudo-membranous candidiasis. The aim of this study is to find a definitive treatment of oral leukoplakia, because of its recurrence and its potentiality to the malignant transformation. There are currently different approaches to oral leukoplakia: scalpel surgery, systemic therapy (carotenoids, vitamins, etc.), electro-cauterization, cryotherapy and the use of the laser. In every lesion, biopsy and histological analysis has been performed to identify the stage and classification of the oral leukoplakia. Laser can be used for the complete excision of the lesion (which is more effective, but also more invasive), for the photodynamic therapy (non-invasive procedure, which requires several applications) or for the vaporization of the lesion (very precise treatment and relatively easy to perform). Laser treatments have shown better healing, less soft tissues retraction and less post-operative pain, comparing with traditional surgery. The use of systemic therapies and smoking habit interruption (where present) has been also useful to reduce the lesions before the clinical treatments. The treatment has always to be supported by histological analysis to identify the risk and consequently planning the clinical approach.

  8. Genetic mutations in accordance with a low malignant potential tumour are not demonstrated in clear cell papillary renal cell carcinoma.

    PubMed

    Raspollini, Maria Rosaria; Castiglione, Francesca; Cheng, Liang; Montironi, Rodolfo; Lopez-Beltran, Antonio

    2016-06-01

    Clear cell papillary renal cell carcinoma (CCPRCC) cases were evaluated for mutations on the following genes: KRAS, NRAS, BRAF, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET and EGFR. Four male and three female patients of age 42-74 years were evaluated. All cases were incidentally detected by ultrasound and ranged 1.8-3.5 cm. Microscopic examination showed variably tubulopapillary, tubular acinar, cystic architecture and the characteristic linear arrangement of nuclei. The cells were reactive with CK7 (strong), CA IX (cup-shape) and 34 β E12. CD10, AMACR/RACEMASE and GATA3 were negative. There were no mutations on any of the investigated genes. This preliminary observation supports the concept that CCPRCC might be indeed an indolent tumour worth it to be named as clear cell papillary neoplasm of low potential. PMID:26941183

  9. Insights into the therapeutic potential of hypoxia-inducible factor-1α small interfering RNA in malignant melanoma delivered via folate-decorated cationic liposomes

    PubMed Central

    Chen, Zhongjian; Zhang, Tianpeng; Wu, Baojian; Zhang, Xingwang

    2016-01-01

    Malignant melanoma (MM) represents the most dangerous form of skin cancer, and its incidence is expected to rise in the coming time. However, therapy for MM is limited by low topical drug concentration and multidrug resistance. This article aimed to develop folate-decorated cationic liposomes (fc-LPs) for hypoxia-inducible factor-1α (HIF-1α) small interfering (siRNA) delivery, and to evaluate the potential of such siRNA/liposome complexes in MM therapy. HIF-1α siRNA-loaded fc-LPs (siRNA-fc-LPs) were prepared by a film hydration method followed by siRNA incubation. Folate decoration of liposomes was achieved by incorporation of folate/oleic acid-diacylated oligochitosans. The resulting siRNA-fc-LPs were 95.3 nm in size with a ζ potential of 2.41 mV. The liposomal vectors exhibited excellent loading capacity and protective effect toward siRNA. The in vitro cell transfection efficiency was almost parallel to the commercially available Lipofectamine™ 2000. Moreover, the anti-melanoma activity of HIF-1α siRNA was significantly enhanced through fc-LPs. Western blot analysis and apoptosis test demonstrated that siRNA-fc-LPs substantially reduced the production of HIF-1α-associated protein and induced the apoptosis of hypoxia-tolerant melanoma cells. Our designed liposomal vectors might be applicable as siRNA delivery vehicle to systemically or topically treat MM. PMID:27042054

  10. Oral soft tissue biopsies in Oporto, Portugal: An eight year retrospective analysis

    PubMed Central

    Guedes, Manuel-Moreira; Albuquerque, Rui; Monteiro, Marta; Lopes, Carlos-Alberto; do Amaral, José-Barbas; Pacheco, José-Júlio

    2015-01-01

    Background The diseases that affect the oral cavity are wide and diverse, comprising a broad spectrum of either benign or malignant lesions. However, few histological-based studies were performed for the evaluation of oral cavity lesions, and very few directed to oral soft tissue pathology. The aim of this study was to carry out pioneering research, within a Portuguese population, to determine the frequency and characteristics of oral malignancies, potential malignant disorders, and soft benign tissues pathologies submitted for biopsy in a north Portugal (Oporto) hospital population. Material and Methods We performed a retrospective study of soft tissue, oral cavity biopsies, in a hospital north of Portugal (Oporto) between 1999 and 2006. We analysed information on gender, age, location of the lesion, and the histopathological diagnosis. Results A total of 1042 oral biopsies were observed, 557(53.5%) in females and 485 (46.5%) in males, with a mean age of 51.7 years (S.D. ±17.6). The topographic location most frequently affected was labial mucosa (n=306). Considering the nature of the lesions, 700 (67.2%) corresponded to non-neoplasic lesions, 45 (4.3%) to potentially malignant disorders, and 297 (28.5%) to neoplasms (93 benign and 204 malignant). Non-neoplasic lesions were more prevalent in female gender (59.9%) when compared with potentially malignant disorders (46.7%) and neoplasms (39.4%) (P< 0.001). Non-neoplasic lesions presented the lower mean age (49.2±17.6) and potentially malignant disorders the highest mean age (60.5±14.5) (P< 0.001). The most common lesion of entire sample was fibro-epithelial hyperplasia (n=186; 17.9%), followed by squamous cell carcinoma (n=158; 15.1%). Conclusions Fibro-epithelial hyperplasia, followed by squamous cell carcinoma, was the most common pathologies. This pioneering study provided, for the first time, data about the proportion of squamous cell carcinoma when compared with benign conditions in a Portuguese hospital

  11. Evaluation of the Antibacterial Potential of Liquid and Vapor Phase Phenolic Essential Oil Compounds against Oral Microorganisms

    PubMed Central

    Wu, Chi-Hao; Ko, Shun-Yao; Chen, Michael Yuanchien; Shih, Yin-Hua; Shieh, Tzong-Ming; Chuang, Li-Chuan; Wu, Ching-Yi

    2016-01-01

    The aim of the present study was to determine the antibacterial activities of the phenolic essential oil (EO) compounds hinokitiol, carvacrol, thymol, and menthol against oral pathogens. Aggregatibacter actinomycetemcomitans, Streptococcus mutans, Methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia. coli were used in this study. The minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), bacterial growth curves, temperature and pH stabilities, and synergistic effects of the liquid and vapor EO compounds were tested. The MIC/MBC of the EO compounds, ranging from the strongest to weakest, were hinokitiol (40–60 μg/mL/40-100 μg/mL), thymol (100–200 μg/mL/200-400 μg/mL), carvacrol (200–400 μg/mL/200-600 μg/mL), and menthol (500-more than 2500 μg/mL/1000-more than 2500 μg/mL). The antibacterial activities of the four EO phenolic compound based on the agar diffusion test and bacterial growth curves showed that the four EO phenolic compounds were stable under different temperatures for 24 h, but the thymol activity decreased when the temperature was higher than 80°C. The combination of liquid carvacrol with thymol did not show any synergistic effects. The activities of the vaporous carvacrol and thymol were inhibited by the presence of water. Continual violent shaking during culture enhanced the activity of menthol. Both liquid and vaporous hinokitiol were stable at different temperatures and pH conditions. The combination of vaporous hinokitiol with zinc oxide did not show synergistic effects. These results showed that the liquid and vapor phases of hinokitiol have strong anti-oral bacteria abilities. Hinokitiol has the potential to be applied in oral health care products, dental materials, and infection controls to exert antimicrobial activity. PMID:27681039

  12. Malignant hyperthermia

    PubMed Central

    2012-01-01

    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. PMID:23198031

  13. Radiopharmacological characterization of ⁶⁴Cu-labeled α-MSH analogs for potential use in imaging of malignant melanoma.

    PubMed

    Gao, Feng; Sihver, Wiebke; Jurischka, Christoph; Bergmann, Ralf; Haase-Kohn, Cathleen; Mosch, Birgit; Steinbach, Jörg; Carta, Davide; Bolzati, Cristina; Calderan, Andrea; Pietzsch, Jens; Pietzsch, Hans-Jürgen

    2016-03-01

    The melanocortin-1 receptor (MC1R) plays an important role in melanoma growth, angiogenesis and metastasis, and is overexpressed in melanoma cells. α-Melanocyte stimulating hormone (α-MSH) and derivatives are known to bind with high affinity at this receptor that provides the potential for selective targeting of melanoma. In this study, one linear α-MSH-derived peptide Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH2 (NAP-NS1) without linker and with εAhx-β-Ala linker, and a cyclic α-MSH derivative, [Lys-Glu-His-D-Phe-Arg-Trp-Glu]-Arg-Pro-Val-NH2 (NAP-NS2) with εAhx-β-Ala linker were conjugated with p-SCN-Bn-NOTA and labeled with (64)Cu. Radiochemical and radiopharmacological investigations were performed with regard to transchelation, stability, lipophilicity and in vitro binding assays as well as biodistribution in healthy rats. No transchelation reactions, but high metabolic stability and water solubility were demonstrated. The linear derivatives showed higher affinity than the cyclic one. [(64)Cu]Cu-NOTA-εAhx-β-Ala-NAP-NS1 ([(64)Cu]Cu-2) displayed rapid cellular association and dissociation in murine B16F10 cell homogenate. All [(64)Cu]Cu-labeled conjugates exhibited affinities in the low nanomolar range in B16F10. [(64)Cu]Cu-2 showed also high affinity in human MeWo and TXM13 cell homogenate. In vivo studies suggested that [(64)Cu]Cu-2 was stable, with about 85 % of intact peptide in rat plasma at 2 h p.i. Biodistribution confirmed the renal pathway as the major elimination route. The uptake of [(64)Cu]Cu-2 in the kidney was 5.9 % ID/g at 5 min p.i. and decreased to 2.0 % ID/g at 60 min p.i. Due to the prospective radiochemical and radiopharmacological properties of the linear α-MSH derivative [(64)Cu]Cu-2, this conjugate is a promising candidate for tracer development in human melanoma imaging.

  14. Evaluation of the mutagenic potential and acute oral toxicity of standardized extract of Ocimum sanctum (OciBest™).

    PubMed

    Chandrasekaran, C V; Srikanth, H S; Anand, M S; Allan, J Joshua; Viji, M M Hipolith; Amit, A

    2013-09-01

    Ocimum sanctum L. (Lamiaceae) is found throughout India and in many parts of world. O. sanctum is used for the treatment of various health indications. In this lieu, it is of prime importance to investigate the safety aspects of the plant. Hence, the present study was conducted to investigate the possible genotoxic potential and acute oral toxicity of the extract of O. sanctum (OciBest™). The standard battery of in vitro genotoxicity tests, namely bacterial reverse mutation, chromosome aberration and micronucleus (MN) tests were employed to assess the possible mutagenic activity. The results showed that OciBest™ (7.9-2500.0 µg/mL) did not increase the number of histidine revertant colonies in Salmonella typhimurium strains (TA98 and TAMix) with and without exogenous metabolic activation (S9). OciBest™ (10.0-100.0 µg/mL) did not show structural chromosomal aberrations or increase in MN induction, with and without S9, at the tested dose range in both 4-h and 18-h exposure cell cultures. Thus, OciBest™ is not genotoxic in bacterial reverse mutation, chromosomal aberration and MN tests. In an acute oral toxicity test, rats were treated with 5 g/kg of OciBest™ and observed for signs of toxicity for 14 days and the results did not show any treatment-related toxic effects to Wistar rats. PMID:23424203

  15. Localization and osteoblastic differentiation potential of neural crest-derived cells in oral tissues of adult mice.

    PubMed

    Ono, Miki; Suzawa, Tetsuo; Takami, Masamichi; Yamamoto, Gou; Hosono, Tomohiko; Yamada, Atsushi; Suzuki, Dai; Yoshimura, Kentaro; Watahiki, Junichi; Hayashi, Ryuhei; Arata, Satoru; Mishima, Kenji; Nishida, Kohji; Osumi, Noriko; Maki, Koutaro; Kamijo, Ryutaro

    2015-09-01

    In embryos, neural crest cells emerge from the dorsal region of the fusing neural tube and migrate throughout tissues to differentiate into various types of cells including osteoblasts. In adults, subsets of neural crest-derived cells (NCDCs) reside as stem cells and are considered to be useful cell sources for regenerative medicine strategies. Numerous studies have suggested that stem cells with a neural crest origin persist into adulthood, especially those within the mammalian craniofacial compartment. However, their distribution as well as capacity to differentiate into osteoblasts in adults is not fully understood. To analyze the precise distribution and characteristics of NCDCs in adult oral tissues, we utilized an established line of double transgenic (P0-Cre/CAG-CAT-EGFP) mice in which NCDCs express green fluorescent protein (GFP) throughout their life. GFP-positive cells were scattered like islands throughout tissues of the palate, gingiva, tongue, and buccal mucosa in adult mice, with those isolated from the latter shown to form spheres, typical cell clusters composed of stem cells, under low-adherent conditions. Furthermore, GFP-positive cells had markedly increased alkaline phosphatase (a marker enzyme of osteoblast differentiation) activity and mineralization as shown by alizarin red staining, in the presence of bone morphogenetic protein (BMP)-2. These results suggest that NCDCs reside in various adult oral tissues and possess potential to differentiate into osteoblastic cells. NCDCs in adults may be a useful cell source for bone regeneration strategies.

  16. Mathematical Models to Explore Potential Effects of Supersaturation and Precipitation on Oral Bioavailability of Poorly Soluble Drugs.

    PubMed

    Kleppe, Mary S; Forney-Stevens, Kelly M; Haskell, Roy J; Bogner, Robin H

    2015-07-01

    Poorly soluble drugs are increasingly formulated into supersaturating drug delivery systems which may precipitate during oral delivery. The link between in vitro drug concentration profiles and oral bioavailability is under intense investigation. The objective of the present work was to develop closed-form analytical solutions that relate in vitro concentration profiles to the amount of drug absorbed using several alternate assumptions and only six parameters. Three parameters define the key features of the in vitro drug concentration-time profile. An additional three parameters focus on physiological parameters. Absorption models were developed based on alternate assumptions; the drug concentration in the intestinal fluid: (1) peaks at the same time and concentration as in vitro, (2) peaks at the same time as in vitro, or (3) reaches the same peak concentration as in vitro. The three assumptions provide very different calculated values of bioavailability. Using Case 2 assumptions, bioavailability enhancement was found to be less than proportional to in silico examples of dissolution enhancement. Case 3 assumptions lead to bioavailability enhancements that are more than proportional to dissolution enhancements. Using Case 1 predicts drug absorption amounts that fall in between Case 2 and 3. The equations developed based on the alternate assumptions can be used to quickly evaluate the potential improvement in bioavailability due to intentional alteration of the in vitro drug concentration vs. time curve by reformulation. These equations may be useful in making decisions as to whether reformulation is expected to provide sufficient bioavailability enhancement to justify the effort.

  17. A potential oral anticancer drug candidate, Moringa oleifera leaf extract, induces the apoptosis of human hepatocellular carcinoma cells

    PubMed Central

    JUNG, IL LAE; LEE, JU HYE; KANG, SE CHAN

    2015-01-01

    It has previously been reported that cold water-extracts of Moringa oleifera leaf have anticancer activity against various human cancer cell lines, including non-small cell lung cancer. In the present study, the anticancer activity of M. oleifera leaf extracts was investigated in human hepatocellular carcinoma HepG2 cells. By the analysis of apoptotic signals, including the induction of caspase or poly(ADP-ribose) polymerase cleavage, and the Annexin V and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays, it was demonstrated that M. oleifera leaf extracts induce the apoptosis of HepG2 cells. In the hollow fiber assay, oral administration of the leaf extracts significantly reduced (44–52%) the proliferation of the HepG2 cells and A549 non-small cell lung cancer cells. These results support the potential of soluble extracts of M. oleifera leaf as orally administered therapeutics for the treatment of human liver and lung cancers. PMID:26622717

  18. Carisoprodol withdrawal syndrome resembling neuroleptic malignant syndrome: Diagnostic dilemma

    PubMed Central

    Paul, Gunchan; Parshotam, Gautam L; Garg, Rajneesh

    2016-01-01

    Soma (Carisoprodol) is N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; a commonly prescribed, centrally acting skeletal muscle relaxant. Neuroleptic malignant syndrome (NMS) is a potentially life-threatening adverse effect of antipsychotic agents. Although diagnostic criteria for NMS have been established, it should be recognized that atypical presentations occur and more flexible diagnostic criteria than currently mandated, may be warranted. We wish to report a postoperative case of bilateral knee replacement who presented with carisoprodol (Soma) withdrawal resembling NMS that was a diagnostic dilemma. Subsequently, it was successfully treated with oral baclofen in absence of sodium dantrolene. PMID:27625493

  19. Carisoprodol withdrawal syndrome resembling neuroleptic malignant syndrome: Diagnostic dilemma.

    PubMed

    Paul, Gunchan; Parshotam, Gautam L; Garg, Rajneesh

    2016-01-01

    Soma (Carisoprodol) is N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; a commonly prescribed, centrally acting skeletal muscle relaxant. Neuroleptic malignant syndrome (NMS) is a potentially life-threatening adverse effect of antipsychotic agents. Although diagnostic criteria for NMS have been established, it should be recognized that atypical presentations occur and more flexible diagnostic criteria than currently mandated, may be warranted. We wish to report a postoperative case of bilateral knee replacement who presented with carisoprodol (Soma) withdrawal resembling NMS that was a diagnostic dilemma. Subsequently, it was successfully treated with oral baclofen in absence of sodium dantrolene. PMID:27625493

  20. Immunotherapy for malignant glioma.

    PubMed

    Suryadevara, Carter M; Verla, Terence; Sanchez-Perez, Luis; Reap, Elizabeth A; Choi, Bryan D; Fecci, Peter E; Sampson, John H

    2015-01-01

    Malignant gliomas (MG) are the most common type of primary malignant brain tumor. Most patients diagnosed with glioblastoma (GBM), the most common and malignant glial tumor, die within 12-15 months. Moreover, conventional treatment, which includes surgery followed by radiation and chemotherapy, can be highly toxic by causing nonspecific damage to healthy brain and other tissues. The shortcomings of standard-of-care have thus created a stimulus for the development of novel therapies that can target central nervous system (CNS)-based tumors specifically and efficiently, while minimizing off-target collateral damage to normal brain. Immunotherapy represents an investigational avenue with the promise of meeting this need, already having demonstrated its potential against B-cell malignancy and solid tumors in clinical trials. T-cell engineering with tumor-specific chimeric antigen receptors (CARs) is one proven approach that aims to redirect autologous patient T-cells to sites of tumor. This platform has evolved dramatically over the past two decades to include an improved construct design, and these modern CARs have only recently been translated into the clinic for brain tumors. We review here emerging immunotherapeutic platforms for the treatment of MG, focusing on the development and application of a CAR-based strategy against GBM.

  1. Potential role of differentially expressed lncRNAs in the pathogenesis of oral squamous cell carcinoma.

    PubMed

    Zhang, Shanchuan; Tian, Lili; Ma, Penghua; Sun, Qiang; Zhang, Kai; GuanchaoWang; Liu, Hongchen; Xu, Baohua

    2015-10-01

    Long non-coding RNAs (lncRNAs) have recently attracted more attention about the role in a broad range of biological processes and complex cancers. We aimed to identify differentially expressed lncRNAs that play an important role in the pathogenesis of oral squamous cell carcinoma (OSCC). Microarray data GSE25099 consisting of 57 samples from patients with OSCC and 22 normal samples were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) and lncRNAs were identified between OSCC samples and control using samr package in R and noncoder software. Co-expression network was constructed for lncRNAs and candidate target DEGs, followed by functional and pathway enrichment analysis using the Database for Annotation, Visualization and Integrated Discovery online tool. OSCC-related genes were screened by Genetic-Association-DB-Database analysis, and then protein-protein interaction (PPI) network construction of OSCC-related and co-expressed genes. Bioinformatic analysis revealed that there were 998 DEGs and 160 differentially expressed lncRNAs between OSCC and normal control. We found LOC100130547, FTH1P3, PDIA3F and GTF2IRD2P1 targeted most of DEGs. Predicted targets-related functional annotation showed significant changes in inflammation-related functions and Toll-like receptor signaling pathway. By further conducting PPI network with lncRNA co-expressed DEGs, we found that OSCC-associated genes including MMP1 (matrix metallopeptidase), MMP3, MMP9, PLAU (plasminogen activator, urokinase) and IL8 (interleukin 8) were targeted by FTH1P3, PDIA3F and GTF2IRD2P1. Our results indicate that lncRNAs FTH1P3, PDIA3F and GTF2IRD2P1 may responsible for progression and metastasis of OSCC via targeting MMP1, MMP3, MMP9, PLAU and IL8 which are key regulators of tumorigenesis. PMID:26276270

  2. Malignant mesothelioma

    PubMed Central

    Ahmed, Ishtiaq; Ahmed Tipu, Salman; Ishtiaq, Sundas

    2013-01-01

    Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor of the pleura and peritoneum with limited knowledge of its natural history. The incidence has increased in the past two decades but still it is a rare tumor. Etiology of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen. Mesothelioma is an insidious neoplasm arising from mesothelial surfaces i.e., pleura (65%-70%), peritoneum (30%), tunica vaginalis testis, and pericardium (1%-2%). The diagnosis of peritoneal and Pleural mesothelioma is often delayed, due to a long latent period between onset and symptoms and the common and nonspecific clinical presentation. The definite diagnosis can only be established by diagnostic laparoscopy or open surgery along with biopsy to obtain histological examination and immunocytochemical analysis. Different treatment options are available but Surgery can achieve a complete or incomplete resection and Radical resection is the preferred treatment. Chemotherapy has an important role in palliative treatment. Photodynamic therapy is also an option under trial. Patients who successfully underwent surgical resection had a considerably longer median survival as well as a significantly higher 5-year survival. Source of Data/Study Selection: The data were collected from case reports, cross-sectional studies, Open-label studies and phase –II trials between 1973-2012. Data Extraction: Web sites and other online resources of American college of surgeons, Medline, NCBI and Medscape resource centers were used to extract data. Conclusion: Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor with limited knowledge of its natural history. The diagnosis of peritoneal and Pleural mesothelioma is often delayed, so level of index of suspicion must be kept high. PMID:24550969

  3. Northwestern profiling of potential translation-regulatory proteins in human breast epithelial cells and malignant breast tissues: evidence for pathological activation of the IGF1R IRES.

    PubMed

    Blume, Scott W; Jackson, Nateka L; Frost, Andra R; Grizzle, William E; Shcherbakov, Oleg D; Choi, Hyoungsoo; Meng, Zheng

    2010-06-01

    Genes involved in the control of cell proliferation and survival (those genes most important to cancer pathogenesis) are often specifically regulated at the translational level, through RNA-protein interactions involving the 5'-untranslated region of the mRNA. IGF1R is a proto-oncogene strongly implicated in human breast cancer, promoting survival and proliferation of tumor cells, as well as metastasis and chemoresistance. Our lab has focused on the molecular mechanisms regulating IGF1R expression at the translational level. We previously discovered an internal ribosome entry site (IRES) within the 5'-untranslated region of the human IGF1R mRNA, and identified and functionally characterized two individual RNA-binding proteins, HuR and hnRNP C, which bind the IGF1R 5'-UTR and differentially regulate IRES activity. Here we have developed and implemented a high-resolution northwestern profiling strategy to characterize, as a group, the full spectrum of sequence-specific RNA-binding proteins potentially regulating IGF1R translational efficiency through interaction with the 5'-untranslated sequence. The putative IGF1R IRES trans-activating factors (ITAFs) are a heterogeneous group of RNA-binding proteins including hnRNPs originating in the nucleus as well as factors tightly associated with ribosomes in the cytoplasm. The IGF1R ITAFs can be categorized into three distinct groups: (a) high molecular weight external ITAFs, which likely modulate the overall conformation of the 5'-untranslated region of the IGF1R mRNA and thereby the accessibility of the core functional IRES; (b) low molecular weight external ITAFs, which may function as general chaperones to unwind the RNA, and (c) internal ITAFs which may directly facilitate or inhibit the fundamental process of ribosome recruitment to the IRES. We observe dramatic changes in the northwestern profile of non-malignant breast cells downregulating IGF1R expression in association with acinar differentiation in 3-D culture

  4. Oral pigmentation: A review

    PubMed Central

    Sreeja, C.; Ramakrishnan, K.; Vijayalakshmi, D.; Devi, M.; Aesha, I.; Vijayabanu, B.

    2015-01-01

    Pigmentations are commonly found in the mouth. They represent in various clinical patterns that can range from just physiologic changes to oral manifestations of systemic diseases and malignancies. Color changes in the oral mucosa can be attributed to the deposition of either endogenous or exogenous pigments as a result of various mucosal diseases. The various pigmentations can be in the form of blue/purple vascular lesions, brown melanotic lesions, brown heme-associated lesions, gray/black pigmentations. PMID:26538887

  5. Oral pigmentation: A review.

    PubMed

    Sreeja, C; Ramakrishnan, K; Vijayalakshmi, D; Devi, M; Aesha, I; Vijayabanu, B

    2015-08-01

    Pigmentations are commonly found in the mouth. They represent in various clinical patterns that can range from just physiologic changes to oral manifestations of systemic diseases and malignancies. Color changes in the oral mucosa can be attributed to the deposition of either endogenous or exogenous pigments as a result of various mucosal diseases. The various pigmentations can be in the form of blue/purple vascular lesions, brown melanotic lesions, brown heme-associated lesions, gray/black pigmentations. PMID:26538887

  6. Radiosensitization by fullerene-C60 dissolved in squalene on human malignant melanoma through lipid peroxidation and enhanced mitochondrial membrane potential

    NASA Astrophysics Data System (ADS)

    Kato, Shinya; Kimura, Masatsugu; Miwa, Nobuhiko

    2014-04-01

    We examined fullerene-C60 dissolved in squalene (C60/Sqe) for the ability to potentiate the radiosensitization under X-ray irradiation on human malignant melanoma HMV-II cells, which were treated with C60/Sqe and thereafter irradiated with X-ray. The cell proliferation for C60/Sqe was inhibited more markedly than for Sqe alone. Meanwhile, cell proliferation was almost unaltered for C60/squalane (Sqa) or Sqa, a hydrogenated form of Sqe, as compared to no-additive control. Thus radiosensitization of C60/Sqe is attributed to peroxidation of unsaturated bonds of squalene by X-ray-excited C60 in contrast to squalane. The fluorescence images of HMV-II cells stained with Rhodamine123, an indicator for mitochondrial membrane potential, were monitored for 6 h after X-ray irradiation. C60/Sqe obviously exhibited more augmented fluorescence intensity on perinuclear region of HMV-II cells than Sqe alone. TBARS assay showed that the lipid peroxidation level as malondialdehyde-equivalent increased by combination of C60/Sqe and X-ray dose-dependently on X-ray doses. C60/Sqe exhibited lipid peroxidation more markedly by 1.2-fold than Sqe alone. Thus the level of lipid peroxidation of squalene was sufficiently higher in C60/Sqe than in Sqe in the absence of C60 under X-ray irradiation, suggesting the combination of C60/Sqe and X-ray irradiation induced radiosensitization on HMV-II cells by peroxidation of absorbed Sqe in mitochondrial membrane via oxidative stress mediated by fullerene-C60.

  7. Reducing the risk of xerostomia and mandibular osteoradionecrosis: the potential benefits of intensity modulated radiotherapy in advanced oral cavity carcinoma.

    PubMed

    Ahmed, Merina; Hansen, Vibeke N; Harrington, Kevin J; Nutting, Christopher M

    2009-01-01

    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.

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

    SciTech Connect

    Ahmed, Merina; Hansen, Vibeke N.; Harrington, Kevin J.; Nutting, Christopher M.

    2009-10-01

    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.

  9. Preclinical comprehensive physicochemical and pharmacokinetic profiling of novel nitroimidazole derivative IIIM-019 - A potential oral treatment for tuberculosis.

    PubMed

    Kour, Gurleen; Kumar, Anil; Singh, Parvinder Pal; Sharma, Sumit; Bhagat, Asha; Vishwakarma, Ram A; Ahmed, Zabeer

    2016-10-01

    New compounds against tuberculosis are urgently needed to combat the crisis of drug resistance in tuberculosis (TB). We have identified a nitrodihydroimidazooxazole analog, IIIM-019 as a new anti-tubercular agent with a MIC of 0.23 μM against H37Rv. Physicochemical properties, in-vitro pharmacokinetics and in-vivo multiple-doses pharmacokinetics were studied for the compound. In silico physicochemical parameters and Lipinski's violations were determined for drug like properties. Lipophilicity was determined experimentally as Octanol-PBS partition coefficient (log P). Passive and active permeability of the compound was determined by PAMPA and Caco-2 cell permeability analysis, respectively. Plasma protein binding was determined by Rapid equilibrium dialysis. Metabolism by liver microsomes revealed the t1/2 and intrinsic clearance of the compound. Hepatotoxicity of IIIM-019 was determined alone and in combination to first line anti-tubercular drugs. The compound was also estimated for nuclear DNA damage. Single doses of IIIM-019 (2.5, 10, 25 and 100 mg/kg) were administered orally to Balb/c mice and the blood samples were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). IIIM-019 exhibited very good lipophilicity (log P) of 2.47 which makes it optimal for oral administration. The compound showed low solubility and permeability and high plasma protein binding. However, it was highly stable in rat liver microsomes with t1/2 > 2 h and very low intrinsic clearance. It was found to be non-hepatotoxic and did not induce any significant DNA damage at high concentrations even up to 100 μM. IIIM-019 showed satisfactory in-vivo pharmacokinetic properties. By increasing the dose from 2.5 mg/kg to 10 mg/kg, AUC0-t increased from 14935 ng h/ml to 81,478 ng h/ml. However the exposure of IIIM-019 in plasma suggested that the levels reached saturation at higher concentrations. The compound showed a good oral bioavailability of 58.7%. The results

  10. [Oral and maxillofacial manifestations of familial adenomatosis polyposis. Gardner's syndrome].

    PubMed

    Wijn, M A; Keller, J J; Brand, H S

    2005-09-01

    Patients suffering from familial adenomatosis polyposis develop multiple pre-malignant gastrointestinal polyps and are at high risk of developing colon cancer. In addition extra-intestinal manifestations are observed frequently. The combination of extra-intestinal manifestations and familial adenomatosis polyposis is named Gardner's syndrome. An early diagnosis of this disease is important because it could mean a better prognosis for the patient. This review describes the oral and maxillofacial symptoms of FAP, and its potential implications for dental treatment. PMID:16184913

  11. Oral Complications in Hematopoietic Stem Cell Recipients: The Role of Inflammation

    PubMed Central

    Haverman, T. M.; Raber-Durlacher, J. E.; Rademacher, W. M. H.; Vokurka, S.; Epstein, J. B.; Huisman, C.; Hazenberg, M. D.; de Soet, J. J.; de Lange, J.; Rozema, F. R.

    2014-01-01

    Hematopoietic stem cell transplantation (HSCT) is widely used as a potentially curative treatment for patients with various hematological malignancies, bone marrow failure syndromes, and congenital immune deficiencies. The prevalence of oral complications in both autologous and allogeneic HSCT recipients remains high, despite advances in transplant medicine and in supportive care. Frequently encountered oral complications include mucositis, infections, oral dryness, taste changes, and graft versus host disease in allogeneic HSCT. Oral complications are associated with substantial morbidity and in some cases with increased mortality and may significantly affect quality of life, even many years after HSCT. Inflammatory processes are key in the pathobiology of most oral complications in HSCT recipients. This review article will discuss frequently encountered oral complications associated with HSCT focusing on the inflammatory pathways and inflammatory mediators involved in their pathogenesis. PMID:24817792

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

    PubMed

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

    2011-08-01

    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.

  13. Recurrent papillary urothelial neoplasm of low malignant potential. Subtle architectural disorder detected by quantitative analysis in DAXX-immunostained tissue sections.

    PubMed

    Castellini, Paolo; Montironi, Maria A; Zizzi, Antonio; Scarpelli, Marina; Mazzucchelli, Roberta; Lopez-Beltran, Antonio; Cheng, Liang; Paone, Nicola; Montironi, Rodolfo

    2014-04-01

    The aim of the study was to identify subtle changes in the so-called architectural predominant order in nonrecurrent and recurrent papillary urothelial neoplasm of low malignant potential (PUNLMP). Quantitative analysis was performed with a software package written in LabVIEW (National Instruments, Austin, TX) in DAXX-immunostained tissue sections. Twelve cases of PUNLMP with papillary fronds sectioned lengthwise through the core were investigated and subdivided as follows: 7 nonrecurrent and 5 recurrent PUNLMP cases. Six cases of normal urothelium (NU) were included. When an epithelial thickness threshold is set at 108 μm (ie, 400 pixels), there is a complete separation between NU and PUNLMP; however, nonrecurrent and recurrent cases fall in the same range of thickness. In setting a nuclear elongation factor threshold at 2.1, there are differences between the 2 PUNLMP groups, recurrent PUNLMP and NU cases, showing a somewhat similar proportion of elongated nuclei. The nuclear orientation separates nonrecurrent from recurrent PUNLMP groups; however, NU cases do not appear as a separate group from the 2 PUNLMP groups. In combining epithelial thickness, nuclear elongation, and orientation in a multivariate analysis, the 2 PUNLMP groups appear separate between them and from NU. NU is less thickened than the 2 PUNLMP groups and shows a combination of elongated and less elongated nuclei. Elongated nuclei are more numerous in nonrecurrent PUNLMP, whereas the nuclei in recurrent PUNLMP are less elongated and less polarized than in the other group. Such finding can be used routinely to identify those PUNLMP patients who will have recurrence.

  14. Autofluorescence imaging in recurrent oral squamous cell carcinoma.

    PubMed

    Scheer, Martin; Fuss, Juliana; Derman, Mehmet Ali; Kreppel, Matthias; Neugebauer, Jörg; Rothamel, Daniel; Drebber, Uta; Zoeller, Joachim E

    2016-03-01

    as gold standard are still needed to get sufficient evidence regarding potential malignancy in patients after multimodal treatment for oral cancer. PMID:26267490

  15. Evaluation of amitrole (aminotriazole) for potential carcinogenicity in orally dosed rats, mice, and golden hamsters

    SciTech Connect

    Steinhoff, D.; Weber, H.; Mohr, U.; Boehme, K.

    1983-06-30

    Amitrole was evaluated for carcinogenic potential in lifespan studies on Wistar rats, NMRI mice, and golden hamsters. At the start of the studies the animals were 6 weeks old. Amitrole was administered, mixed with pulverized chow, at dietary concentrations of 0, 1, 10, and 100 micrograms/g (ppm). Each treated group and control group consisted of 75 male and 75 female rats and mice and of 76 male and 76 female golden hamsters. Additional animals were used to evaluate the functional state of the thyroid. Somewhat lower body weights, slightly reduced survival times, and transient effects on thyroid function were observed in golden hamsters at 100 ppm. In mice, a slight increase in pituitary gland hyperemias was seen at 100 ppm; also an effect on thyroid function usually occurred at the same concentration. In rats, a very large number of cystic dilatations of follicles in the thyroid at 100 ppm and a dose-unrelated increase in hemorrhages and hyperemias in the pituitary gland were indicative of an effect of amitrole on these organs. The strongest effect of amitrole on thyroid function, as compared to golden hamsters and mice, was seen in rats at 100 ppm. At this concentration a highly increased number of thyroid and pituitary gland tumors was observed in rats. In golden hamsters and mice, no tumor induction was seen.

  16. Techniques for early diagnosis of oral squamous cell carcinoma: Systematic review

    PubMed Central

    Carreras-Torras, Clàudia

    2015-01-01

    Background and objectives The diagnosis of early oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC) is of paramount clinical importance given the mortality rate of late stage disease. The aim of this study is to review the literature to assess the current situation and progress in this area. Material and Methods A search in Cochrane and PubMed (January 2006 to December 2013) has been used with the key words “squamous cell carcinoma”, “early diagnosis” “oral cavity”, “Potentially Malignant Disorders” y “premalignant lesions”. The inclusion criteria were the use of techniques for early diagnosis of OSCC and OPMD, 7 years aged articles and publications written in English, French or Spanish. The exclusion criteria were case reports and studies in other languages. Results Out of the 89 studies obtained initially from the search 60 articles were selected to be included in the systematic review: 1 metaanalysis, 17 systematic reviews, 35 prospective studies, 5 retrospective studies, 1 consensus and 1 semi-structured interviews. Conclusions The best diagnostic technique is that which we have sufficient experience and training. Definitely tissue biopsy and histopathological examination should remain the gold standard for oral cancer diagnose. In this systematic review it has not been found sufficient scientific evidence on the majority of proposed techniques for early diagnosis of OSCC, therefore more extensive and exhaustive studies are needed. Key words: Squamous cell carcinoma, early diagnosis, oral cavity, potentially malignant disorders, premalignant lesions. PMID:25662554

  17. Assessment of Oral Toxicity and Safety of Pentamethylchromanol (PMCol), A Potential Chemopreventative Agent, in Rats and Dogs

    PubMed Central

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

    2010-01-01

    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 500 mg/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

  18. Verrucous Carcinoma with Oral Submucous Fibrosis: A Rare Case with Brief Review.

    PubMed

    Komal, Khot; Deshmukh, Siddharth B; Deshmukh, Anjum

    2015-08-01

    Oral verrucous carcinoma (VC) is a variant of well differentiated oral squamous cell carcinoma (OSCC) characterized by exophytic over growth. Oral submucous fibrosis (OSMF) is a potentially malignant disorder associated with chronic betel nut chewing habit. The development of OSCC is seen in one-third of the OSMF patients, but the development of VC is rare in such patients. There are very few cases of OSMF with VC reported in literature. Here, present a rare case of an elderly patient with VC in conjunction with OSMF.

  19. Verrucous Carcinoma with Oral Submucous Fibrosis: A Rare Case with Brief Review

    PubMed Central

    Komal, Khot; Deshmukh, Anjum

    2015-01-01

    Oral verrucous carcinoma (VC) is a variant of well differentiated oral squamous cell carcinoma (OSCC) characterized by exophytic over growth. Oral submucous fibrosis (OSMF) is a potentially malignant disorder associated with chronic betel nut chewing habit. The development of OSCC is seen in one-third of the OSMF patients, but the development of VC is rare in such patients. There are very few cases of OSMF with VC reported in literature. Here, present a rare case of an elderly patient with VC in conjunction with OSMF. PMID:26468468

  20. Minor Salivary Gland Changes in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma - A Histopathological Study

    PubMed Central

    Chitturi, Ravi Teja; Ragunathan, Yoithapprabhunath Thukanayakanpalayam; Lakshmi, Suman Jhansi; Nallusamy, Jaisanghar; Joseph, Isaac

    2016-01-01

    Introduction The most common etiology for Oral Squamous Cell Carcinoma (OSCC) is tobacco and tobacco related products which cause nuclear damage to the keratinocytes. The chemical carcinogens not only affect the lining of oral epithelium but also affect the lining epithelium of the excretory ducts of the salivary glands. Thus, there is a possibility of epithelial dysplasia of the salivary duct epithelium which may lead to potential malignant transformation. Aim The study was performed to see the changes in the minor salivary glands and excretory ducts in cases of oral epithelial dysplasia and OSCC. Materials and Methods A total of 278 archival cases of mild, moderate and severe epithelial dysplasia, carcinoma in situ, OSCC including verrucous carcinoma were histopathologically evaluated to observe changes in the excretory ducts and the minor salivary glands. Results In the study there were 56.5% males and 43.5% females. The age group that was most commonly affected in both the sexes was 50-60 yr old. Buccal mucosa was the most common site of involvement. Ductal changes observed in the excretory duct include simple hyperplasia, metaplastic changes such as mucous, oncocytic & squamous, and infiltration of inflammatory cells and malignant cells. Acinar changes observed were degeneration, squamous metaplasia, myoepithelial cell proliferation and inflammatory cell infiltration. Both the excretory ducts and ducts within the gland showed dysplasia. Conclusion According to observations in our study it is suggested that histopathological interpretation for oral mucosal lesions especially oral epithelial dysplasias and OSCC should also include changes related to salivary gland tissue to provide a better treatment plan and prevent recurrence of the malignant tumours. PMID:27630945

  1. Minor Salivary Gland Changes in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma - A Histopathological Study

    PubMed Central

    Chitturi, Ravi Teja; Ragunathan, Yoithapprabhunath Thukanayakanpalayam; Lakshmi, Suman Jhansi; Nallusamy, Jaisanghar; Joseph, Isaac

    2016-01-01

    Introduction The most common etiology for Oral Squamous Cell Carcinoma (OSCC) is tobacco and tobacco related products which cause nuclear damage to the keratinocytes. The chemical carcinogens not only affect the lining of oral epithelium but also affect the lining epithelium of the excretory ducts of the salivary glands. Thus, there is a possibility of epithelial dysplasia of the salivary duct epithelium which may lead to potential malignant transformation. Aim The study was performed to see the changes in the minor salivary glands and excretory ducts in cases of oral epithelial dysplasia and OSCC. Materials and Methods A total of 278 archival cases of mild, moderate and severe epithelial dysplasia, carcinoma in situ, OSCC including verrucous carcinoma were histopathologically evaluated to observe changes in the excretory ducts and the minor salivary glands. Results In the study there were 56.5% males and 43.5% females. The age group that was most commonly affected in both the sexes was 50-60 yr old. Buccal mucosa was the most common site of involvement. Ductal changes observed in the excretory duct include simple hyperplasia, metaplastic changes such as mucous, oncocytic & squamous, and infiltration of inflammatory cells and malignant cells. Acinar changes observed were degeneration, squamous metaplasia, myoepithelial cell proliferation and inflammatory cell infiltration. Both the excretory ducts and ducts within the gland showed dysplasia. Conclusion According to observations in our study it is suggested that histopathological interpretation for oral mucosal lesions especially oral epithelial dysplasias and OSCC should also include changes related to salivary gland tissue to provide a better treatment plan and prevent recurrence of the malignant tumours.

  2. Subthalamic and Cortical Local Field Potentials Associated with Pilocarpine-Induced Oral Tremor in the Rat

    PubMed Central

    Long, Lauren L.; Podurgiel, Samantha J.; Haque, Aileen F.; Errante, Emily L.; Chrobak, James J.; Salamone, John D.

    2016-01-01

    Tremulous jaw movements (TJMs) are rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus. In rodents, TJMs are induced by neurochemical conditions that parallel those seen in human Parkinsonism, including neurotoxic or pharmacological depletion of striatal dopamine (DA), DA antagonism, and cholinomimetic administration. Moreover, TJMs in rodents can be attenuated by antiparkinsonian agents, including levodopa (L-DOPA), DA agonists, muscarinic antagonists, and adenosine A2A antagonists. In human Parkinsonian patients, exaggerated physiological synchrony is seen in the beta frequency band in various parts of the cortical/basal ganglia/thalamic circuitry, and activity in the tremor frequency range (3–7 Hz) also has been recorded. The present studies were undertaken to determine if tremor-related local field potential (LFP) activity could be recorded from motor cortex (M1) or subthalamic nucleus (STN) during the TJMs induced by the muscarinic agonist pilocarpine, which is a well-known tremorogenic agent. Pilocarpine induced a robust TJM response that was marked by rhythmic electromyographic (EMG) activity in the temporalis muscle. Compared to periods with no tremor activity, TJM epochs were characterized by increased LFP activity in the tremor frequency range in both neocortex and STN. Tremor activity was not associated with increased synchrony in the beta frequency band. These studies identified tremor-related LFP activity in parts of the cortical/basal ganglia circuitry that are involved in the pathophysiology of Parkinsonism. This research may ultimately lead to identification of the oscillatory neural mechanisms involved in the generation of tremulous activity, and promote development of novel treatments for tremor disorders. PMID:27378874

  3. In vivo detection of oral epithelial cancer using endogenous fluorescence lifetime imaging: a pilot human study (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Jo, Javier A.; Hwang, Dae Yon; Palma, Jorge; Cheng, Shuna; Cuenca, Rodrigo; Malik, Bilal; Jabbour, Joey; Cheng, Lisa; Wright, John; Maitland, Kristen

    2016-03-01

    Endogenous fluorescence lifetime imaging (FLIM) provides direct access to the concomitant functional and biochemical changes accompanying tissue transition from benign to precancerous and cancerous. Since FLIM can noninvasively measure different and complementary biomarkers of precancer and cancer, we hypothesize that it will aid in clinically detecting early oral epithelial cancer. Our group has recently demonstrated the detection of benign from premalignant and malignant lesions based on endogenous multispectral FLIM in the hamster cheek-pouch model. Encouraged by these positive preliminary results, we have developed a handheld endoscope capable of acquiring multispectral FLIM images in real time from the oral mucosa. This novel FLIM endoscope is being used for imaging clinically suspicious pre-malignant and malignant lesions from patients before undergoing tissue biopsy for histopathological diagnosis of oral epithelial cancer. Our preliminary results thus far are already suggesting the potential of endogenous FLIM for distinguishing a variety of benign lesions from advanced dysplasia and squamous cell carcinoma (SCC). To the best of out knowledge, this is the first in vivo human study aiming to demonstrate the ability to predict the true malignancy of clinically suspicious lesions using endogenous FLIM. If successful, the resulting clinical tool will allow noninvasive real-time detection of epithelial precancerous and cancerous lesions in the oral mucosa and could potentially be used to assist at every step involved on the clinical management of oral cancer patients, from early screening and diagnosis, to treatment and monitoring of recurrence.

  4. Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

    PubMed Central

    Tanaka, Takuji; Tanaka, Mayu; Tanaka, Takahiro

    2011-01-01

    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. PMID:21660266

  5. Oral curcumin mitigates the clinical and neuropathologic phenotype of the Trembler-J mouse: a potential therapy for inherited neuropathy.

    PubMed

    Khajavi, Mehrdad; Shiga, Kensuke; Wiszniewski, Wojciech; He, Feng; Shaw, Chad A; Yan, Jiong; Wensel, Theodore G; Snipes, G Jackson; Lupski, James R

    2007-09-01

    Mutations in myelin genes cause inherited peripheral neuropathies that range in severity from adult-onset Charcot-Marie-Tooth disease type 1 to childhood-onset Dejerine-Sottas neuropathy and congenital hypomyelinating neuropathy. Many myelin gene mutants that cause severe disease, such as those in the myelin protein zero gene (MPZ) and the peripheral myelin protein 22 gene (PMP22), appear to make aberrant proteins that accumulate primarily within the endoplasmic reticulum (ER), resulting in Schwann cell death by apoptosis and, subsequently, peripheral neuropathy. We previously showed that curcumin supplementation could abrogate ER retention and aggregation-induced apoptosis associated with neuropathy-causing MPZ mutants. We now show reduced apoptosis after curcumin treatment of cells in tissue culture that express PMP22 mutants. Furthermore, we demonstrate that oral administration of curcumin partially mitigates the severe neuropathy phenotype of the Trembler-J mouse model in a dose-dependent manner. Administration of curcumin significantly decreases the percentage of apoptotic Schwann cells and results in increased number and size of myelinated axons in sciatic nerves, leading to improved motor performance. Our findings indicate that curcumin treatment is sufficient to relieve the toxic effect of mutant aggregation-induced apoptosis and improves the neuropathologic phenotype in an animal model of human neuropathy, suggesting a potential therapeutic role in selected forms of inherited peripheral neuropathies. PMID:17701891

  6. Positive/negative surface charge of chitosan based nanogels and its potential influence on oral insulin delivery.

    PubMed

    Wang, Juan; Xu, Mengxue; Cheng, Xiaojie; Kong, Ming; Liu, Ya; Feng, Chao; Chen, Xiguang

    2016-01-20

    To develop insulin delivery system for the treatment of diabetes, two insulin-loaded nanogels with opposite zeta potential (-15.94 ± 0.449 mV for insulin:CMCS/CS-NGs(-) and +17.15 ± 0.492 mV for insulin:CMCS/CS-NGs(+)) were obtained. Ex vivo results showed that the nanogels with opposite surface charge exhibited different adhesion and permeation in specific intestinal segments. There was no significant differences in adhesion and permeation in rat duodenum, but in rat jejunum, insulin:CMCS/CS-NGs(-) exhibited enhanced adhesion and permeation, which were about 3 folds (adhesion) and 1.7 folds (permeation) higher than insulin:CMCS/CS-NGs(+). These results demonstrated that the surface charge property of nanogels determined the absorption sites of CMCS/CS-NGs in small intestine. In vivo study, the blood glucose level in insulin:CMCS/CS-NGs(-) group had 3 mmol/L lower than insulin:CMCS/CS-NGs(+) group during 1h to 11h after the oral administration, which demonstrated that negative insulin:CMCS/CS-NGs had a better management of blood glucose than positive ones. PMID:26572423

  7. MicroRNAs in oral lichen planus and potential miRNA-mRNA pathogenesis with essential cytokines: a review.

    PubMed

    Ma, Hui; Wu, Yuanqin; Yang, Huamei; Liu, Jiajia; Dan, Hongxia; Zeng, Xin; Zhou, Yu; Jiang, Lu; Chen, Qianming

    2016-08-01

    Oral lichen planus (OLP) is a potentially premalignant condition with unknown pathogenesis. Immune and inflammatory factors are thought to play important roles in the development of OLP, and cytokines, such as interferon (IFN)-γ and tumor necrosis factor (TNF)-α, can act as critical players in the immunopathogenesis of OLP. MicroRNAs (miRNAs) are closely correlated with cytokines in various inflammation-related diseases. In patients with OLP, miRNA-146a and miRNA-155 are increased in peripheral blood mononuclear cells, and numerous miRNAs have been shown to exhibit altered expression profiles in lesions. Although the microRNA-messenger RNA (miRNA-mRNA) network is thought to be involved in the development of OLP, in-depth studies are lacking. Here, we summarize current data on the mechanisms of action of miRNAs regulating typical cytokines in OLP, including interleukin (IL)-10, IL-17, IL-22, IFN-γ, and TNF-α, to study the genetic basis of the pathogenesis of OLP and to provide prospects of therapy. PMID:27282956

  8. Novel mucus-penetrating liposomes as a potential oral drug delivery system: preparation, in vitro characterization, and enhanced cellular uptake

    PubMed Central

    Li, Xiuying; Chen, Dan; Le, Chaoyi; Zhu, Chunliu; Gan, Yong; Hovgaard, Lars; Yang, Mingshi

    2011-01-01

    Background The aim of this study was to investigate the intestinal mucus-penetrating properties and intestinal cellular uptake of two types of liposomes modified by Pluronic F127 (PF127). Methods The two types of liposomes, ie, PF127-inlaid liposomes and PF127-adsorbed liposomes, were prepared by a thin-film hydration method followed by extrusion, in which coumarin 6 was loaded as a fluorescence marker. A modified Franz diffusion cell mounted with the intestinal mucus of rats was used to study the diffusion characteristics of the two types of PF127 liposomes. Cell uptake studies were conducted in Caco-2 cells and analyzed using confocal laser scanning microcopy as well as flow cytometry. Results The diffusion efficiency of the two types of PF127-modified liposomes through intestinal rat mucus was 5–7-fold higher than that of unmodified liposomes. Compared with unmodified liposomes, PF127-inlaid liposomes showed significantly higher cellular uptake of courmarin 6. PF127-adsorbed liposomes showed a lower cellular uptake. Moreover, and interestingly, the two types of PF127-modified liposomes showed different cellular uptake mechanisms in Caco-2 cells. Conclusion PF127-inlaid liposomes with improved intestinal mucus-penetrating ability and enhanced cellular uptake might be a potential carrier candidate for oral drug delivery. PMID:22163166

  9. Biochemical markers in oral submucous fibrosis: A review and update

    PubMed Central

    Kamath, V V; Satelur, K; Komali, Y

    2013-01-01

    Oral submucous fibrosis (OSMF) is a potentially malignant oral condition effectively linked to the causative habit of chewing areca nut. Since its first description in the 1950s, numerous epidemiological, biochemical, histological, and genetic studies have been reported. While most studies point out to the cause and effect of areca nut, co-additive factors are also implicated in the progression and malignant transformation of this condition. Biochemical investigations have concentrated on outlining such changes in the blood, serum or tissues of these patients and have given insights on the possible pathogenesis of OSMF. This article attempts to compile details of biochemical investigations in OSMF and summarize and infer on the findings. PMID:24348612

  10. Putting a finger on potential predictors of oral contraceptive side effects: 2D:4D and middle-phalangeal hair.

    PubMed

    Oinonen, Kirsten A

    2009-06-01

    Many women experience emotional or physical side effects when taking oral contraceptives (OCs). Despite the potential impact on women's health and well-being, there are no valid methods to screen women for their risk of OC side effects. The present paper presents the results of two studies where anthropometric indicators of androgen exposure, 2D:4D and middle-phalangeal hair, were examined for their potential as predictors of OC side effects. In study 1, 2D:4D was associated with women's reports of a history of: (a) negative mood side effects; (b) discontinuation due to negative mood side effects; (c) specific mood side effects (i.e., crying, sadness, and altered trust in one's partners) and (d) specific physical side effects (i.e., headaches, fatigue, and decreased sex drive). In study 2, 2D:4D and/or middle-phalangeal hair was/were associated with a reported history of: (a) discontinuation due to negative mood side effects; (b) specific mood-related side effects (i.e., negative mood, disrupted sleep, increased aggression, and altered trust in one's partner) and (c) specific physical side effects (i.e., headaches, decreased menstrual cramps, and increased sex drive/arousal). The general pattern was that adverse OC side effects were experienced by women with lower 2D:4D and fewer middle-phalangeal hairs. Almost all relationships remained significant when response bias was controlled. These results suggest a possible role for prenatal testosterone exposure and both androgen action and sensitivity in women's experience of OC side effects. Furthermore, these two digit measures may be useful predictors of hormonal contraceptive side effects in women. PMID:19131172

  11. Development and characterization of a novel nanoemulsion drug-delivery system for potential application in oral delivery of protein drugs

    PubMed Central

    Sun, Hongwu; Liu, Kaiyun; Liu, Wei; Wang, Wenxiu; Guo, Chunliang; Tang, Bin; Gu, Jiang; Zhang, Jinyong; Li, Haibo; Mao, Xuhu; Zou, Quanming; Zeng, Hao

    2012-01-01

    Background: The stability of protein drugs remains one of the key hurdles to their success in the market. The aim of the present study was to design a novel nanoemulsion drug-delivery system (NEDDS) that would encapsulate a standard-model protein drug – bovine serum albumin (BSA) – to improve drug stability. Methods: The BSA NEDDS was prepared using a phase-inversion method and pseudoternary phase diagrams. The following characteristics were studied: morphology, size, zeta potential, drug loading, and encapsulation efficiency. We also investigated the stability of the BSA NEDDS, bioactivity of BSA encapsulated within the NEDDS, the integrity of the primary, secondary, and tertiary structures, and specificity. Results: The BSA NEDDS consisted of Cremophor EL-35, propylene glycol, isopropyl myristate, and normal saline. The average particle diameter of the BSA NEDDS was about 21.8 nm, and the system showed a high encapsulation efficiency (>90%) and an adequate drug-loading capacity (45 mg/mL). The thermodynamic stability of the system was investigated at different temperatures and pH levels and in room-temperature conditions for 180 days. BSA NEDDS showed good structural integrity and specificity for the primary, secondary, and tertiary structures, and good bioactivity of the loaded BSA. Conclusions: BSA NEDDS showed the properties of a good nanoemulsion-delivery system. NEDDS can greatly enhance the stability of the protein drug BSA while maintaining high levels of drug bioactivity, good specificity, and integrity of the primary, secondary, and tertiary protein structures. These findings indicate that the nanoemulsion is a potential formulation for oral administration of protein drugs. PMID:23118537

  12. AGS67E, an Anti-CD37 Monomethyl Auristatin E Antibody–Drug Conjugate as a Potential Therapeutic for B/T-Cell Malignancies and AML: A New Role for CD37 in AML

    PubMed Central

    Pereira, Daniel S.; Guevara, Claudia I.; Jin, Liqing; Mbong, Nathan; Verlinsky, Alla; Hsu, Ssucheng J.; Aviña, Hector; Karki, Sher; Abad, Joseph D.; Yang, Peng; Moon, Sung-Ju; Malik, Faisal; Choi, Michael Y.; An, Zili; Morrison, Kendall; Challita-Eid, Pia M.; Doñate, Fernando; Joseph, Ingrid B.J.; Kipps, Thomas J.; Dick, John E.; Stover, David R.

    2015-01-01

    CD37 is a tetraspanin expressed on malignant B cells. Recently, CD37 has gained interest as a therapeutic target. We developed AGS67E, an antibody–drug conjugate that targets CD37 for the potential treatment of B/T-cell malignancies. It is a fully human monoclonal IgG2 antibody (AGS67C) conjugated, via a protease-cleavable linker, to the microtubule-disrupting agent mono-methyl auristatin E (MMAE). AGS67E induces potent cytotoxicity, apoptosis, and cell-cycle alterations in many non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) cell lines and patient-derived samples in vitro. It also shows potent antitumor activity in NHL and CLL xenografts, including Rituxan-refractory models. During profiling studies to confirm the reported expression of CD37 in normal tissues and B-cell malignancies, we made the novel discovery that the CD37 protein was expressed in T-cell lymphomas and in AML. AGS67E bound to >80% of NHL and T-cell lymphomas, 100% of CLL and 100% of AML patient-derived samples, including CD34+CD38− leukemic stem cells. It also induced cytotoxicity, apoptosis, and cell-cycle alterations in AML cell lines and antitumor efficacy in orthotopic AML xenografts. Taken together, this study shows not only that AGS67E may serve as a potential therapeutic for B/T-cell malignancies, but it also demonstrates, for the first time, that CD37 is well expressed and a potential drug target in AML. PMID:25934707

  13. 1’-Acetoxychavicol acetate inhibits growth of human oral carcinoma xenograft in mice and potentiates cisplatin effect via proinflammatory microenvironment alterations

    PubMed Central

    2012-01-01

    Background Oral cancers although preventable, possess a low five-year survival rate which has remained unchanged over the past three decades. In an attempt to find a more safe, affordable and effective treatment option, we describe here the use of 1’S-1’-acetoxychavicol acetate (ACA), a component of Malaysian ginger traditionally used for various medicinal purposes. Methods Whether ACA can inhibit the growth of oral squamous cell carcinoma (SCC) cells alone or in combination with cisplatin (CDDP), was explored both in vitro using MTT assays and in vivo using Nu/Nu mice. Occurrence of apoptosis was assessed using PARP and DNA fragmentation assays, while the mode of action were elucidated through global expression profiling followed by Western blotting and IHC assays. Results We found that ACA alone inhibited the growth of oral SCC cells, induced apoptosis and suppressed its migration rate, while minimally affecting HMEC normal cells. ACA further enhanced the cytotoxic effects of CDDP in a synergistic manner as suggested by combination index studies. We also found that ACA inhibited the constitutive activation of NF-κB through suppression of IKKα/β activation. Human oral tumor xenografts studies in mice revealed that ACA alone was as effective as CDDP in reducing tumor volume, and further potentiated CDDP effects when used in combination with minimal body weight loss. The effects of ACA also correlated with a down-regulation of NF-κB regulated gene (FasL and Bim), including proinflammatory (NF-κB and COX-2) and proliferative (cyclin D1) biomarkers in tumor tissue. Conclusion Overall, our results suggest that ACA inhibits the growth of oral SCC and further potentiates the effect of standard CDDP treatment by modulation of proinflammatory microenvironment. The current preclinical data could form the basis for further clinical trials to improve the current standards for oral cancer care using this active component from the Malaysian ginger. PMID:23043547

  14. [Oral viral infections].

    PubMed

    Parent, Dominique

    2016-02-01

    Exclude herpes infection in the presence of acute oral ulcers of unknown origin, particularly in patients in poor general condition. Remember that asymptomatic HSV-1 shedding in saliva may result in an oral-genital transmission. Perform an anogenital examination and a screening for other sexually transmitted diseases when oral warts are diagnosed. Search for immunosuppression and monitor the patient (screening for a potential associated carcinoma) when there is rapid growth of oral warts. Consider all the clinical signs (systemic, skin, other mucosa, immunity...) when a patient has an enanthem or oral ulcerations. Ask for a HIV test when an oral Kaposi's sarcoma, a hairy leukoplakia or major aphthae are diagnosed. PMID:26854091

  15. Immunohistochemical expression of p16 protein in oral squamous cell carcinoma and lichen planus.

    PubMed

    Salehinejad, Jahanshah; Sharifi, Nourieh; Amirchaghmaghi, Maryam; Ghazi, Narges; Shakeri, Mohammad Taghi; Ghazi, Ala

    2014-08-01

    Epithelial carcinogenesis is a multistep process. Specific genetic events lead to malignant transformation of oral epithelium. Oral squamous cell carcinoma (OSCC) may be preceded by potentially malignant lesions such as oral lichen planus (OLP). The p16 protein functions as a negative regulator of the cell cycle progression. Altered pattern of p16 serves as a biomarker for oral mucosal dysplasia and malignant growth. The purpose of this study was to evaluate p16 expression in OSCC and OLP to determine whether it can be a useful marker for early detection of carcinogenesis. We examined p16 expression in 45 OSCCs (15 grade I, 15 grade II, and 15 grade III), 15 OLPs without dysplasia, and 8 normal mucosal specimens with immunohistochemistry. p16 was interpreted as positive if more than 70% of tumor cells showed brown nuclear and cytoplasmic staining. All of the OSCC and control group samples showed negative immunoreactivity, whereas 26.7% of OLP samples were positive for p16. Our findings suggest that p16 expression could not be used as a helpful marker for detection of development toward malignancy in OLP samples. PMID:24850170

  16. Assessing the utility of autofluorescence-based pulmonary optical endomicroscopy to predict the malignant potential of solitary pulmonary nodules in humans

    PubMed Central

    Seth, Sohan; Akram, Ahsan R.; McCool, Paul; Westerfeld, Jody; Wilson, David; McLaughlin, Stephen; Dhaliwal, Kevin; Williams, Christopher K. I.

    2016-01-01

    Solitary pulmonary nodules are common, often incidental findings on chest CT scans. The investigation of pulmonary nodules is time-consuming and often leads to protracted follow-up with ongoing radiological surveillance, however, clinical calculators that assess the risk of the nodule being malignant exist to help in the stratification of patients. Furthermore recent advances in interventional pulmonology include the ability to both navigate to nodules and also to perform autofluorescence endomicroscopy. In this study we assessed the efficacy of incorporating additional information from label-free fibre-based optical endomicrosopy of the nodule on assessing risk of malignancy. Using image analysis and machine learning approaches, we find that this information does not yield any gain in predictive performance in a cohort of patients. Further advances with pulmonary endomicroscopy will require the addition of molecular tracers to improve information from this procedure. PMID:27550539

  17. Assessing the utility of autofluorescence-based pulmonary optical endomicroscopy to predict the malignant potential of solitary pulmonary nodules in humans.

    PubMed

    Seth, Sohan; Akram, Ahsan R; McCool, Paul; Westerfeld, Jody; Wilson, David; McLaughlin, Stephen; Dhaliwal, Kevin; Williams, Christopher K I

    2016-01-01

    Solitary pulmonary nodules are common, often incidental findings on chest CT scans. The investigation of pulmonary nodules is time-consuming and often leads to protracted follow-up with ongoing radiological surveillance, however, clinical calculators that assess the risk of the nodule being malignant exist to help in the stratification of patients. Furthermore recent advances in interventional pulmonology include the ability to both navigate to nodules and also to perform autofluorescence endomicroscopy. In this study we assessed the efficacy of incorporating additional information from label-free fibre-based optical endomicrosopy of the nodule on assessing risk of malignancy. Using image analysis and machine learning approaches, we find that this information does not yield any gain in predictive performance in a cohort of patients. Further advances with pulmonary endomicroscopy will require the addition of molecular tracers to improve information from this procedure. PMID:27550539

  18. In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria

    PubMed Central

    Suzuki, Shigeo; Hikosaka, Kenji; Balogun, Emmanuel O.; Komatsuya, Keisuke; Niikura, Mamoru; Kobayashi, Fumie; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo

    2015-01-01

    5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe2+) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug. PMID:26324278

  19. Preservation of high phenylalanine ammonia lyase activities in roots of Japanese Striped corn: a potential oral therapeutic to treat phenylketonuria.

    PubMed

    López-Villalobos, Arturo; Lücker, Joost; López-Quiróz, Ana Angela; Yeung, Edward C; Palma, Kristoffer; Kermode, Allison R

    2014-06-01

    Phenylketonuria (PKU) is an inherited metabolic disorder caused by deficient phenylalanine hydroxylase (PAH) activity, the enzyme responsible for the disposal of excess amounts of the essential amino acid phenylalanine (Phe). Phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) has potential to serve as an enzyme substitution therapy for this human genetic disease. Using 7-day-old Japanese Striped corn seedlings (Japonica Striped maize, Zea mays L. cv. japonica) that contain high activities of PAL, we investigated a number of methods to preserve the roots as an intact food and for long-term storage. The cryoprotectant effects of maple syrup and other edible sugars (mono- and oligosaccharides) were evaluated. Following thawing, the preserved roots were then examined to determine whether the rigid plant cell walls could protect the PAL enzyme from proteolysis during simulated (in vitro) digestion comprised of gastric and intestinal phases. While several treatments led to retention of PAL activity during freezing, upon thawing and in vitro digestion, root tissues that had been previously frozen in the presence of maple syrup exhibited the highest residual PAL activities (∼50% of the initial enzyme activity), in marked contrast to all of the treatments using other edible sugars. The structural integrity of the root cells, and the stability of the functional PAL tetramer were also preserved with the maple syrup protocol. These results have significance for the formulation of oral enzyme/protein therapeutics. When plant tissues are adequately preserved, the rigid cell walls constitute a protective barrier even under harsh (e.g. gastrointestinal-like) conditions.

  20. Lesions with unclear malignant potential (B3) after minimally invasive breast biopsy: evaluation of vacuum biopsies performed in Switzerland and recommended further management

    PubMed Central

    Haueisen, Harald; Kampmann, Gert; Oehlschlegel, Christian; Seifert, B; Rageth, Luzi; Rageth, Christoph; Stadlmann, S; Kubik-Huch, Rahel A

    2015-01-01

    Background Histopathological B3 lesions after minimal invasive breast biopsy (VABB) are a particular challenge for the clinician, as there are currently no binding recommendations regarding the subsequent procedure. Purpose To analyze all B3 lesions, diagnosed at VABB and captured in the national central Swiss MIBB database and to provide a data basis for further management in this subgroup of patients. Material and Methods All 9,153 stereotactically, sonographically, or magnetic resonance imaging (MRI)-guided vacuum-assisted breast biopsies, performed in Switzerland between 2009 and 2011, captured in a central database, were evaluated. The rate of B3 lesions and the definitive pathological findings in patients who underwent surgical resection were analyzed. Results The B3 rate was 17.0% (1532 of 9000 biopsies with B classification). Among the 521 lesions with a definitive postoperative diagnosis, the malignancy rate (invasive carcinoma or DCIS) was 21.5%. In patients with atypical ductal hyperplasia, papillary lesions, flat epithelial atypia, lobular neoplasia, and radial scar diagnosed by VABB, the malignancy rates were 25.9%, 3.1%, 18.3%, 26.4%, and 11.1%, respectively. Conclusion B3 lesions, comprising 17%, of all analyzed biopsies, were common and the proportion of malignancies in those lesions undergoing subsequent surgical excision was high (21.5%). PMID:26552694

  1. Narrow band imaging: clinical applications in oral and oropharyngeal cancer.

    PubMed

    Vu, A; Farah, C S

    2016-07-01

    Narrow Band Imaging (NBI) is an endoscopic optical imaging enhancement technology that improves the contrast of mucosal surface texture, and enhances visualisation of mucosal and submucosal vasculature. White light is filtered to emit two 30-nm narrow bands of blue (415 nm) and green light (540 nm) light simultaneously, the former corresponding to the main peak absorption spectrum of haemoglobin, and the latter allowing visualisation of blood vessels in the deeper mucosal and submucosal layers. NBI has been used to better assess oral potentially malignant disorders (OPMD), identify oral and oropharyngeal squamous cell carcinoma (SCC), and to define surgical margins of head and neck malignancies. NBI shows great potential in improving detection rates of OPMD, facilitating better assessment of oral and oropharyngeal SCC, and reducing the risk of recurrence for oral SCC. Although further research is required to better understand and define intrapapillary capillary loop (IPCL) patterns and to relate these with clinical, histopathological and molecular parameters especially for early mucosal changes, there is building evidence to recommend its use as the new gold standard for endoscopic assessment in head and neck oncology. PMID:26713751

  2. Oral Cancer-related Inherited Cancer Syndromes: A Comprehensive Review.

    PubMed

    Sarode, Gargi S; Batra, Akshit; Sarode, Sachin C; Yerawadekar, Sujata; Patil, Shankargouda

    2016-01-01

    Oral squamous cell carcinoma is the most common malignancy of the oral cavity, which is usually preceded by a myriad of oral potentially malignant disorders (OPMDs). In the classification of OPMDs, inherited cancer syndromes (ICSs) were proposed as one of the categories. Inherited cancer syndromes are genetic disorders in which inherited genetic mutation in one or more genes predispose the affected individuals to the development of cancer and may also cause its early onset. Many of these syndromes are caused by mutations in tumor suppressor genes, oncogenes, and genes involved in angiogenesis. General dental practitioners frequently come across OPMDs in their day-to-day practice. It becomes of paramount importance to have knowledge about these rare but prognostically important OPMDs. With this view in mind, in this article, efforts have been made to comprehensively discuss about various ICSs that have higher potential of transformation into oral cancer. The ICSs discussed in this article are xeroderma pigmentosum (XP), ataxia telangiectasia (AT), Bloom syndrome (BS), Fanconi's anemia (FA), and Li-Fraumeni syndrome (LFS), with special emphasis on signs, symptoms, and genetic considerations. PMID:27484606

  3. Reconstruction of a full-thickness collagen-based human oral mucosal equivalent.

    PubMed

    Kinikoglu, Beste; Auxenfans, Céline; Pierrillas, Pascal; Justin, Virginie; Breton, Pierre; Burillon, Carole; Hasirci, Vasif; Damour, Odile

    2009-11-01

    Tissue engineered human oral mucosa has the potential to be applied to the closure of surgical wounds after tissue deficits due to facial trauma, malignant lesion surgery or preposthetic procedure. It can also be used to elucidate the biology and pathology of oral mucosa and as a model alternative to animals for safety testing of oral care products. Using the technology previously developed in our laboratory for the production of a skin equivalent, we were able to reconstruct a nonkeratinized full-thickness human oral mucosal equivalent closely mimicking human native oral mucosa. The successive coculture of human lamina propria fibroblasts and human oral epithelial cells isolated from the nonkeratinized region of oral cavity in a porous collagen-glycosaminoglycan (GAG)-chitosan scaffold gave rise to a lamina propria equivalent (LPE) and then to an oral mucosa equivalent (OME). The results of the histology, immunohistology and transmission electron microscopy of this OME demonstrated the presence of a nonkeratinized pluristratified and differentiated epithelium as in native nonkeratinized human oral mucosa expressing both K13 and K3/76. This epithelium was firmly anchored to the LPE by a continuous and ultrastructurally well-organized basement membrane. In the LPE, fibroblasts synthesized new extracellular matrix where the average collagen fibre diameter was 28.4 nm, close to that of native oral mucosa. The proliferative capacity of the basal cells was demonstrated by the expression of Ki67. PMID:19698987

  4. Glucose tolerance factor extracted from yeast: oral insulin-mimetic and insulin-potentiating agent: in vivo and in vitro studies.

    PubMed

    Weksler-Zangen, Sarah; Mizrahi, Tal; Raz, Itamar; Mirsky, Nitsa

    2012-09-01

    In search for an effective oral treatment for diabetes, we examined the capacity of glucose tolerance factor (GTF) extracted from yeast and administered orally to reduce hyperglycaemia in rat models exhibiting insulin deficiency. The cellular effect of GTF on the insulin signalling pathway was investigated in vitro. GTF (oral bolus), insulin (intraperitoneal) or their combination was administered to streptozotocin-diabetic (STZ) or hyperglycaemic Cohen diabetic-sensitive (hyp-CDs) rats. Blood glucose (BG) and insulin levels were measured in the postprandial (PP) state and during an oral glucose tolerance test. Deoxy-glucose transport and insulin signal transduction were assessed in 3T3-L1 adipocytes and myoblasts incubated with the GTF. Low dose of insulin produced a 34 and 12·5 % reduction in the PP-BG levels of hyp-CDs and STZ rats, respectively. GTF induced a 33 and 17 % reduction in the PP-BG levels of hyp-CDs and STZ rats, respectively. When combined with insulin, a respective decrease (58 and 42 %) in BG levels was observed, suggesting a partially additive (hyp-CDs) or synergistic (STZ rats) effect of the GTF and insulin. GTF did not induce insulin secretion in hyp-CDs rats, yet it lowered their BG levels, proposing an effect on glucose clearance by peripheral tissues. GTF induced a dose-dependent increase in deoxy-glucose transport into myoblasts and fat cells similar to insulin, while the combined treatment resulted in augmented transport rate. GTF induced a dose- and time-dependent phosphorylation of insulin receptor substrate 1, Akt and mitogen-activated protein kinase independent of insulin receptor phosphorylation. GTF exerts remarkable insulin-mimetic and insulin-potentiating effects, both in vivo and in vitro. It produces an insulin-like effect by acting on cellular signals downstream of the insulin receptor. These results demonstrate a potential source for a novel oral medication for diabetes.

  5. Stenting in Malignant Biliary Obstruction.

    PubMed

    Almadi, Majid A; Barkun, Jeffrey S; Barkun, Alan N

    2015-10-01

    Decompression of the biliary system in patients with malignant biliary obstruction has been widely accepted and implemented as part of the care. Despite a wealth of literature, there remains a significant amount of uncertainty as to which approach would be most appropriate in different clinical settings. This review covers stenting of the biliary system in cases of resectable or palliative malignant biliary obstruction, potential candidates for biliary drainage, technical aspects of the procedure, as well as management of biliary stent dysfunction. Furthermore, periprocedural considerations including proper mapping of the location of obstruction and the use of antibiotics are addressed.

  6. Pediatric Salivary Gland Malignancies.

    PubMed

    Ord, Robert A; Carlson, Eric R

    2016-02-01

    Pediatric malignant salivary gland tumors are extremely rare. The percentage of malignant tumors is higher than that seen in adults, although the outcomes in terms of survival are better in pediatric patients. The mainstay of treatment is surgical excision with negative margins. This article reviews current concepts in demographics, etiology, management, and outcomes of malignant salivary tumors in children.

  7. The potential role of oral pH in the persistence of Trichomonas gallinae in Cooper's Hawks (Accipiter cooperii).

    PubMed

    Urban, Elizabeth H; Mannan, R William

    2014-01-01

    Trichomoniasis, caused by the protozoan Trichomonas gallinae, affects a variety of species worldwide including avivorious raptors. Existing information suggests that the disease is most prevalent in young birds, and differential susceptibility to trichomoniasis among individuals in different age groups was documented in Cooper's Hawks (Accipiter cooperii) nesting in Tucson, Arizona. In that population, 85% of nestling Cooper's Hawks had T. gallinae in their oral cavity, compared to only 1% of breeding-age hawks. Trichomonads generally are sensitive to environmental pH and we explored the possibility that differences in oral pH may contribute to the differential prevalence of infection between age groups. We measured the pH of the fluid in the oral cavity in 375 Cooper's Hawks from three age groups (nestlings, fledglings, and breeding age) in Tucson, Arizona, in 2010 and 2011 and clinically tested for T. gallinae in a subsample of hawks. Oral pH of nestlings (∼ 6.8) was 7.3 times less acidic than in fledgling or breeding Cooper's Hawks (∼ 6.1). The incidence of T. gallinae was higher in nestlings (16%) than in either fledglings or breeding hawks (0%). Our findings indicate that oral pH becomes more acidic in Cooper's Hawks soon after they leave the nest. Trichomonas gallinae thrives when pH is between 6.5 and 7.5 (optimum 7.2), but is less viable in more acidic conditions. Higher levels of acidity in the oral cavity of fledglings and breeding Cooper's Hawks may reduce their susceptibility to trichomoniasis, and play a role in the differential prevalence of infection among age groups.

  8. Primary Malignant Melanoma of Maxilla: Report of a Case with Discussion

    PubMed Central

    Rani, G. Shirisha; Kumar, T. Vinay; Begum, Md Rezwana; Priya Srinivasan, Anu

    2014-01-01

    Primary oral malignant melanoma, very rare neoplasm of melanocytic origin, usually presents as a bluish black to tan-brown colored lesion Which is accounting for 0.2 to 8% of all melanomas, 1.6% of all head and neck malignancies, and 0.5% of all oral neoplasia. In general, the prognosis of oral melanoma is poor and worse than that of cutaneous melanoma. Here a case of oral malignant melanoma is presented, which was undetected during the first visit to a dental clinic. When a simple oral surgical treatment was carried out in that region, it resulted in the appearance of a massive pigmented lesion which was histopathologically diagnosed as malignant melanoma. This paper is presented to reemphasize the fact that any pigmented lesion in the oral cavity should be viewed with suspicion and proper investigation (biopsy) should be carried out to rule out any untoward experiences later. PMID:25642350

  9. Enhanced oral bioavailability of a sterol-loaded microemulsion formulation of Flammulina velutipes, a potential antitumor drug

    PubMed Central

    Yi, Chengxue; Zhong, Hui; Tong, Shanshan; Cao, Xia; Firempong, Caleb K; Liu, Hongfei; Fu, Min; Yang, Yan; Feng, Yingshu; Zhang, Huiyun; Xu, Ximing; Yu, Jiangnan

    2012-01-01

    Purpose To investigate the growth inhibition activity of Flammulina velutipes sterol (FVS) against certain human cancer cell lines (gastric SGC and colon LoVo) and to evaluate the optimum microemulsion prescription, as well as the pharmacokinetics of encapsulated FVS. Methods Molecules present in the FVS isolate were identified by gas chromatography/mass spectrometry analysis. The cell viability of FVS was assessed with methyl thiazolyl tetrazolium (MTT) bioassay. Based on the solubility study, phase diagram and stability tests, the optimum prescription of F. velutipes sterol microemulsions (FVSMs) were determined, followed by FVSMs characterization, and its in vivo pharmacokinetic study in rats. Results The chemical composition of FVS was mainly ergosterol (54.8%) and 22,23-dihydroergosterol (27.9%). After 72 hours of treatment, both the FVS (half-maximal inhibitory concentration [IC50] = 11.99 μg · mL−1) and the standard anticancer drug, 5-fluorouracil (IC50 = 0.88 μg · mL−1) exhibited strong in vitro antiproliferative activity against SGC cells, with IC50 > 30.0 μg · mL−1; but the FVS performed poorly against LoVo cells (IC50 > 40.0 μg · mL−1). The optimal FVSMs prescription consisted of 3.0% medium chain triglycerides, 5.0% ethanol, 21.0% Cremophor EL and 71.0% water (w/w) with associated solubility of FVS being 0.680 mg · mL−1 as compared to free FVS (0.67 μg · mL−1). The relative oral bioavailability (area-under-the-curve values of ergosterol and 22,23-dihydroergosterol showed a 2.56-fold and 4.50-fold increase, respectively) of FVSMs (mean diameter ~ 22.9 nm) as against free FVS were greatly enhanced. Conclusion These results indicate that the FVS could be a potential candidate for the development of an anticancer drug and it is readily bioavailable via microemulsion formulations. PMID:23049254

  10. Oral Leukoplakia – Is Biopsy at the Initial Appointment a Must?

    PubMed Central

    Mutalik, Vimi S.; Pai, Keerthilatha M; Naikmasur, Venkatesh G.; Phaik, Khoo Suan

    2014-01-01

    Background: Oral leukoplakia is a potentially malignant disorder of the oral cavity. Leukoplakias with chances of undergoing malignant transformation owing to the presence of dysplastic changes may not be clinically distinguishable from leukoplakias without dysplasia. The study was carried out to evaluate the usefulness of biopsy in assessing the clinico-pathologic correlations of oral leukoplakia at the patient’s initial visit. Materials and Methods: Hospital records with clinical diagnosis of oral leukoplakia were retrospectively analysed. All these patients had undergone biopsy in their initial visit. Histopathological slides were reviewed and reported by a single pathologist. Diagnosis agreement was considered to be present if the clinical diagnosis matched the histopathological diagnosis. Misdiagnosis was considered if the clinical diagnosis did not match the histopathological diagnosis and underdiagnosis when malignancy was detected on histopathological examination. Results: A total of 115 patients were clinically diagnosed with oral leukoplakia. According to clinical appearance of the leukoplakia patch was categorized in to three types viz homogeneous leukoplakia (n= 24 i.e. 20.87%), speckled leukoplakia (n=76 i.e. 66.08%) and verrucous leukoplakia (n=15 i.e. 13.04%). Histopathological examination confirmed clinical diagnosis in 88 cases (a diagnosis agreement of 76.52%). Histopathological examination of 19 cases revealed a different diagnosis, thus categorized as misdiagnosis (16.52%) and 8 cases had unexpected malignancy which accounted for underdiagnosis in 6.96% cases. There was dysplasia in 45 (51.13%) of the histopathologically confirmed cases of leukoplakia. Conclusion: The clinical appearance of suspicious white lesions does not provide a true nature of its disease status and malignant changes may be missed. PMID:25302256

  11. Expression of MMP-1/PAR-1 and patterns of invasion in oral squamous cell carcinoma as potential prognostic markers

    PubMed Central

    Fan, Hai-Xia; Chen, Yan; Ni, Bo-Xiong; Wang, Shan; Sun, Miao; Chen, Dong; Zheng, Jin-Hua

    2015-01-01

    Background Matrix metalloproteinase (MMP)-1 degrades type I collagen of the extracellular matrix and also activates protease activated receptor (PAR)-1 to induce angiogenesis. The aims of this study were to evaluate microvessel density (MVD) and the expression of PAR-1 and MMP-1 in oral squamous cell carcinoma (SCC) specimens with different patterns of invasion (POI) and to evaluate their association with clinical outcomes. Methods Seventy-four surgically obtained oral SCC samples were classified by POI according to hematoxylin-eosin staining. MVD and the localization and intensity of PAR-1 and MMP-1 expression were detected by immunohistochemistry. Results Of the 74 oral SCC samples, 18, 5, 34, and 17 showed type I, II, III, and IV POI, respectively. MVD and expression levels of MMP-1 and PAR-1 differed between POI types I–II and POI types III–IV. Patients with low tumor expression of MMP-1 and PAR-1 and low MVD had a longer survival time than those with high tumor expression of MMP-1 and PAR-1. Moreover, the survival time of patients with POI types III–IV was shorter than that of patients with POI types I–II. Conclusion POI combined with expression levels of MMP-1 and PAR-1 may be a valuable tool for assessing the clinical prognosis of patients with oral SCC. PMID:26170698

  12. Partially erupted third molars as a potential source of infection in patients receiving peripheral stem cell transplantation for malignant diseases: a retrospective study.

    PubMed

    Ohman, David; Björk, Yvonne; Bratel, John; Kristiansson, Camilla; Johansson, Peter; Johansson, Jan-Erik; Brune, Mats; Hasséus, Bengt

    2010-02-01

    Forty-four patients with malignant diseases for which they received peripheral stem cell transplant therapy (PSCT) were retrospectively studied regarding local and systemic infection originating from around partially erupted third molars (PEMs). Twenty-two patients had one or more PEMs, while 22 patients had none. Data were retrieved from medical and dental records. Systemic and local signs of infection and treatment were assessed. We recorded the number of transplanted CD34(+) blood stem cells, days with white blood cell counts < 0.5 x 10(9) l(-1), days until engraftment, maximum level of C-reactive protein (CRP), days with fever, positive blood cultures, days taking antibiotics, days drinking < 0.5 l, days of total parenteral nutrition, days receiving intravenously administered analgesics, and number of admission days. No statistically significant difference was detected between patients with PEMs and those without PEMs regarding any of the studied parameters. Of patients with PEMs, 36% (8 of 22) developed local infections around PEMs during the PSCT period. The study indicates that PEMs pose no significant risk of causing systemic infection in patients receiving PSCT for malignant diseases but increase the risk of developing a local infection, justifying close supervision and early treatment in cases of local infection during PSCT treatment. PMID:20156265

  13. Neuroleptic malignant syndrome.

    PubMed

    Ingall, T J; Tennant, C

    1986-11-01

    The neuroleptic malignant syndrome is a relatively rare but potentially fatal complication of the use of major tranquillizers; mortality may be as high as 20%. The syndrome is manifest by the onset of hyperpyrexia, muscular rigidity and tremor, impaired consciousness and autonomic dysfunction. The pathophysiology is thought to be by way of dopamine receptor blockade. The syndrome is managed by cessation of the neuroleptic medication, by supportive measures and by instituting treatment with one or more of a number of specific drugs whose use is based on theoretical considerations rather than empirical evidence of efficacy; these drugs include anticholinergics, L-dopa, bromocriptine amantidine and dantrolene sodium. Although not proven, early recognition and treatment may reduce both the mortality and the longer term morbidity of this syndrome. PMID:3773831

  14. Potential role of autophagy in smokeless tobacco extract-induced cytotoxicity and in morin-induced protection in oral epithelial cells.

    PubMed

    Ganguli, Arnab; Das, Amlan; Nag, Debasish; Bhattacharya, Surela; Chakrabarti, Gopal

    2016-04-01

    Toxic components of STE induced serious, adverse human oral health outcomes. In the present study, we observed that STE was involved in oral toxicity by reducing the viability of human squamous epithelial cells, SCC-25, along with the simultaneous induction of both apoptosis and autophagic signaling. STE was also found to induce significant amount ROS generation in SCC-25 cells. The dietary flavonoid morin, found abundantly in a variety of herbs, fruits and wine, has been reported to attenuate ROS-induced pathogenesis including autophagy. In this study we designed three different treatment regimes of morin treatment, such as pre, co, and post - treatment of STE challenged SCC-25 cells. In all cases morin provided cytoprotection to STE challenged SCC-25 cells by augmenting STE induced ROS-dependent cytotoxic autophagy. Hence, morin is a potential option for antioxidant therapy in treatment of STE induced toxicity. PMID:26891815

  15. Long-term oral administration of memory-enhancing doses of tacrine in mice: a study of potential toxicity and side effects.

    PubMed

    Fitten, L J; Flood, J F; Baxter, C F; Tachiki, K H; Perryman, K

    1987-11-01

    Recently, tacrine (1, 2, 3, 4-tetrahydro-9-aminoacridine; THA; TAC) has received international attention as an oral agent capable of relieving some of the cognitive symptoms accompanying Alzheimer's disease (AD). When given acutely and parenterally (by injection), tacrine has also enhanced memory retention in animals and man. This study evaluates the clinical potential of this agent by assessing toxicity and major side effects of a memory-enhancing dose of tacrine in mice. Groups of mice received either tacrine or vehicle (placebo) orally for 4 to 6 months. A lack of toxicity after this prolonged treatment with TAC was indicated by: (a) no significant impairment on a battery of behavioral toxicity tests; (b) improved memory retention; (c) a significant but only slight elevation of ornithine transcarbamylase activity in blood serum; (d) no abnormality as revealed with light microscopy of liver tissue; and (e) no gross organ pathology in visceral organs.

  16. The role of estrogen receptor {beta} (ER{beta}) in malignant diseases-A new potential target for antiproliferative drugs in prevention and treatment of cancer

    SciTech Connect

    Warner, Margaret; Gustafsson, Jan-Ake

    2010-05-21

    The discovery of ER{beta} in the middle of the 1990s represents a paradigm shift in our understanding of estrogen signaling. It has turned out that estrogen action is not mediated by one receptor, ER{alpha}, but by two balancing factors, ER{alpha} and ER{beta}, which are often antagonistic to one another. Excitingly, ER{beta} has been shown to be widespread in the body and to be involved in a multitude of physiological and pathophysiological events. This has led to a strong interest of the pharmaceutical industry to target ER{beta} by drugs against various diseases. In this review, focus is on the role of ER{beta} in malignant diseases where the anti proliferative activity of ER{beta} gives hope of new therapeutic approaches.

  17. Oral Lesions and Lymphoproliferative Disorders

    PubMed Central

    Castellarin, P.; Pozzato, G.; Tirelli, G.; Di Lenarda, R.; Biasotto, M.

    2010-01-01

    Lymphoproliferative disorders are heterogeneous malignancy characterized by the expansion of a lymphoid clone more or less differentiated. At the level of the oral cavity, the lymphoproliferative disorder can occur in various ways, most commonly as lymphoid lesions with extranodal externalization, but sometimes, oral lesions may represent a localization of a disease spread. With regard to the primary localizations of lymphoproliferative disorders, a careful examination of the head and neck, oral, and oropharyngeal area is necessary in order to identify suspicious lesions, and their early detection results in a better prognosis for the patient. Numerous complications have been described and frequently found at oral level, due to pathology or different therapeutic strategies. These complications require precise diagnosis and measures to oral health care. In all this, oral pathologists, as well as dental practitioners, have a central role in the treatment and long-term monitoring of these patients. PMID:20871659

  18. Potential role of linagliptin as an oral once-daily treatment for patients with type 2 diabetes

    PubMed Central

    Hoimark, Lene; Laursen, Torben; Rungby, Jørgen

    2012-01-01

    Background: Linagliptin is an oral antihyperglycemic agent that selectively inhibits the enzyme dipeptidyl peptidase-4 (DPP-4). Inhibition of DPP-4 increases the levels of the incretin hormones glucagon-like peptide and glucose-dependent insulinotropic polypeptide by preventing their degradation. Objective: We reviewed the role of linagliptin as an oral once-daily treatment for patients with type 2 diabetes. Methods: A comprehensive literature search was performed using the term “linagliptin.” Original research articles and review articles were included in our examination. Results: Linagliptin has a similar mode of action as other gliptins, with comparable efficacy, safety profile, and tolerability. Differences in pharmacokinetic parameters that distinguish linagliptin from other gliptins include that linagliptin is not renally excreted and does not require dose reduction with renal impairment. Conclusion: Linagliptin is an oral, once-daily, antihyperglycemic agent that significantly reduces glycated hemoglobin (HbA1c) when used alone or in combination with other antidiabetic drugs in people with type 2 diabetes. Pharmacokinetics, such as the lack of renal excretion, distinguishes linagliptin from other gliptins. PMID:22952411

  19. Malignant Tumors of Tongue in Iranian Population

    PubMed Central

    Akbari, Mohammad Esmaeil; Atarbashi Moghadam, Saede; Atarbashi Moghadam, Fazele; Bastani, Zahra

    2016-01-01

    Background The incidence of oral cancers varies from one country to another, which can be clarified by the difference in the distribution of the risk factors and the possible etiologies. Tongue is a main segment of oral cavity and malignant lesions of this region accounts for nearly 30% of all oral cancers. Objectives In the present study, we evaluated the pattern of tongue cancer in Iranian population and compared these findings with those previously reported in the other countries. Methods In this multicenter, retrospective cross-sectional study recorded cases of the malignant tongue tumors in the cancer research center (CRC) of Shahid Beheshti University of Medical Sciences were extracted. The patient records and their microscopic reports were retrieved from the archives and age, sex and microscopic types were evaluated. It is to be noted that the CRC has been serving as a cancer registry center for major hospitals all over the country since the year of 2003. Thus, the obtained statistics are highly reliable. Results During the years 2003 to 2008, a total number of 952 new cases of the tongue cancer were recorded in the CRC. Most cases are diagnosed in the sixth and seventh decades of life. 450 cases (47.2%) occurred in men and 489 cases (51.36%) in women. Four different types of malignant lesions (epithelial, salivary gland, hematopoietic and mesenchymal) were diagnosed. Epithelial tumors were the most prevalent malignancies (93%) of which squamous cell carcinoma (SCC) made up 87.39% of all lesions. Salivary gland tumors had the second place with 3.15% of the total lesions. Conclusions In Iranian population, squamous cell carcinoma is the most prevalent malignancy of tongue and it is notable that the ratio of female to male population was equal. These lesions were prevalent in the sixth and seventh decades of life. Thus screening examination of tongue by dentist especially in elderly patients is necessary for early detection of cancerous lesions. PMID:27761209

  20. Management of malignant hyperthermia: diagnosis and treatment

    PubMed Central

    Schneiderbanger, Daniel; Johannsen, Stephan; Roewer, Norbert; Schuster, Frank

    2014-01-01

    Malignant hyperthermia is a potentially lethal inherited disorder characterized by disturbance of calcium homeostasis in skeletal muscle. Volatile anesthetics and/or the depolarizing muscle relaxant succinylcholine may induce this hypermetabolic muscular syndrome due to uncontrolled sarcoplasmic calcium release via functionally altered calcium release receptors, resulting in hypoxemia, hypercapnia, tachycardia, muscular rigidity, acidosis, hyperkalemia, and hyperthermia in susceptible individuals. Since the clinical presentation of malignant hyperthermia is highly variable, survival of affected patients depends largely on early recognition of the symptoms characteristic of malignant hyperthermia, and immediate action on the part of the attending anesthesiologist. Clinical symptoms of malignant hyperthermia, diagnostic criteria, and current therapeutic guidelines, as well as adequate management of anesthesia in patients susceptible to malignant hyperthermia, are discussed in this review. PMID:24868161

  1. Estimation of Pyruvic acid in serum and saliva among healthy and potentially malignant disorder subjects – a stepping stone for cancer screening?

    PubMed Central

    Bhat, Anithraj; Prasad, Kakarla; Trivedi, Dhiraj; Acharya, Swathi

    2015-01-01

    Background According to Warburg’s effect, the rate of glycolysis increases in cancerous cells. This will increase overall levels of pyruvic acid. The present on-going study was conducted to estimate the levels of pyruvic acid in saliva and serum in normal, oral PMD subjects. Material and Methods A total of 50 subjects in healthy, PMD of the oral cavity individuals were selected based on clinical and histological criteria. Collected saliva and serum samples were subjected to pyruvic acid level estimation using biochemical analysis. Results Of the 50 participants 25 (13: Males; 12: Females) & 25 (16: Males; 9: Females) were PMD group. Independent samples t test showed statistically significant difference in serum & salivary pyruvic acid level in between 2 groups (p < 0.001 respectively). Conclusions Estimation of pyruvic acid showed sequential increase in the level in PMD group compared to healthy. Hence the study results open new direction in cancer screening. Key words:Pyruvic acid, glycolysis, warburg’s effect. PMID:26535090

  2. Oral Leukoplakia as It Relates to HPV Infection: A Review

    PubMed Central

    Feller, L.; Lemmer, J.

    2012-01-01

    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. PMID:22505902

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

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

    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.

  4. Optical fiber Raman-based spectroscopy for oral lesions characterization: a pilot study

    NASA Astrophysics Data System (ADS)

    Carvalho, Luis Felipe C. S.; Neto, Lázaro P. M.; Oliveira, Inajara P.; Rangel, João. Lucas; Ferreira, Isabelle; Kitakawa, Dárcio; Martin, Airton A.

    2016-03-01

    In the clinical daily life various lesions of the oral cavity have shown different aspects, generating an inconclusive or doubtful diagnosis. In general, oral injuries are diagnosed by histopathological analysis from biopsy, which is an invasive procedure and does not gives immediate results. In the other hand, Raman spectroscopy technique it is a real time and minimal invasive analytical tool, with notable diagnostic capability. This study aims to characterize, by optical fiber Raman-based spectroscopy (OFRS), normal, inflammatory, potentially malignant, benign and malign oral lesions. Raman data were collected by a Holospec f / 1.8 spectrograph (Kayser Optical Systems) coupled to an optical fiber, with a 785nm laser line source and a CCD Detector. The data were pre-processed and vector normalized. The average analysis and standard deviation was performed associated with cluster analysis and compared to the histopalogical results. Samples of described oral pathological processes were used in the study. The OFRS was efficient to characterized oral lesions and normal mucosa, in which biochemical information related to vibrational modes of proteins, lipids, nucleic acids and carbohydrates were observed. The technique (OFRS) is able to demonstrate biochemical information concern different types of oral lesions showing that Raman spectroscopy could be useful for an early and minimal invasive diagnosis.

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

    PubMed Central

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

    2005-01-01

    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

  6. Collecting and Storing Malignant, Borderline Malignant Neoplasms, and Related Samples From Young Patients With Cancer

    ClinicalTrials.gov

    2016-05-13

    Acute Undifferentiated Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Acute Lymphoblastic Leukemia; Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies; Childhood Chronic Myelogenous Leukemia; Chronic Lymphocytic Leukemia; Hairy Cell Leukemia; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Neoplasm of Uncertain Malignant Potential; Prolymphocytic Leukemia; Secondary Acute Myeloid Leukemia; T-cell Large Granular Lymphocyte Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  7. Potential involvement of miR-375 in the premalignant progression of oral squamous cell carcinoma mediated via transcription factor KLF5.

    PubMed

    Shi, Wen; Yang, Jing; Li, Siyuan; Shan, Xiaofeng; Liu, Xiaosong; Hua, Hong; Zhao, Chuanke; Feng, Zhendong; Cai, Zhigang; Zhang, Lihe; Zhou, Demin

    2015-11-24

    To elucidate the genetic effect involved in the premalignant progression of chronic inflammation to cancer, we performed microRNA and mRNA profiling in oral lichen planus (OLP), oral squamous cell carcinoma (OSCC), and normal tissue from the same patients. We demonstrate the involvement of a suppressive microRNA, miR-375, in the regulation of this premalignant progression via KLF5, a transcription factor that modulates the expression of genes contributing to proliferation and apoptosis. We found that miR-375 abundance decreased in tissues with progression from the normal state to OLP and subsequently to OSCC. Restoration of miR-375 by transduction of a synthetic mimic into OSCC cells repressed cellular proliferation and promoted apoptosis, with concomitant down-regulation of KLF5, and vice versa. The direct binding of miR-375 to the 3'-untranslated region of KLF5 was further confirmed. Additionally, Survivin (BIRC5), a target of KLF5, was also regulated by miR-375, explaining the susceptibility of miR-375-mimic transfected cells to apoptosis. Further analysis of clinical specimens suggested that expression of KLF5 and BIRC5 is up-regulated during the progression from inflammation to cancer. Our findings provide novel insights into the involvement of microRNAs in progression of inflammation to carcinoma and suggest a potential early-stage biomarker or therapy target for oral carcinoma. PMID:26474386

  8. Effects of amitriptyline and intra-oral device appliance on clinical and laser-evoked potentials features in chronic tension-type headache.

    PubMed

    de Tommaso, M; Shevel, E; Libro, G; Guido, M; Di Venere, D; Genco, S; Monetti, C; Serpino, C; Barile, G; Lamberti, P; Livrea, P

    2005-05-01

    In the present study, we examined clinical and laser-evoked potentials (LEP) features in two groups of chronic tension-type headache (CTTH) patients treated with two different approaches: intra-oral appliance of prosthesis, aiming to reduce muscular tenderness, and 10 mg daily amitriptyline. Eighteen patients suffering from CTTH (IHS, 2004) participated in the study. We performed a basal evaluation of clinical features and LEPs in all patients (T0) vs. 12 age- and sex-matched controls; successively, patients were randomly assigned to a two-month treatment by amitriptyline or intra-oral device appliance. The later LEPs, especially the P2 component, were significantly increased in amplitude in the CTTH group. Both the intra-oral prosthesis and amitriptyline significantly reduced headache frequency. Total Tenderness Score was significantly reduced in the group treated by the prosthesis. The amplitude of P2 response elicited by stimulation of pericranial zones showed a reduction after amitriptyline treatment. The results of this study may confirm that pericranial tenderness is primarily a phenomenon initiating a self-perpetuating circuit, favoured by central sensitisation at the level of the cortical nociceptive areas devoted to the attentive and emotive compounds of pain. Both the interventions at the peripheral and central levels may interrupt this reverberating circuit, improving the outcome of headache. PMID:15926017

  9. Effects of amitriptyline and intra-oral device appliance on clinical and laser-evoked potentials features in chronic tension-type headache.

    PubMed

    de Tommaso, M; Shevel, E; Libro, G; Guido, M; Di Venere, D; Genco, S; Monetti, C; Serpino, C; Barile, G; Lamberti, P; Livrea, P

    2005-05-01

    In the present study, we examined clinical and laser-evoked potentials (LEP) features in two groups of chronic tension-type headache (CTTH) patients treated with two different approaches: intra-oral appliance of prosthesis, aiming to reduce muscular tenderness, and 10 mg daily amitriptyline. Eighteen patients suffering from CTTH (IHS, 2004) participated in the study. We performed a basal evaluation of clinical features and LEPs in all patients (T0) vs. 12 age- and sex-matched controls; successively, patients were randomly assigned to a two-month treatment by amitriptyline or intra-oral device appliance. The later LEPs, especially the P2 component, were significantly increased in amplitude in the CTTH group. Both the intra-oral prosthesis and amitriptyline significantly reduced headache frequency. Total Tenderness Score was significantly reduced in the group treated by the prosthesis. The amplitude of P2 response elicited by stimulation of pericranial zones showed a reduction after amitriptyline treatment. The results of this study may confirm that pericranial tenderness is primarily a phenomenon initiating a self-perpetuating circuit, favoured by central sensitisation at the level of the cortical nociceptive areas devoted to the attentive and emotive compounds of pain. Both the interventions at the peripheral and central levels may interrupt this reverberating circuit, improving the outcome of headache.

  10. Potential involvement of miR-375 in the premalignant progression of oral squamous cell carcinoma mediated via transcription factor KLF5

    PubMed Central

    Li, Siyuan; Shan, Xiaofeng; Liu, Xiaosong; Hua, Hong; Zhao, Chuanke; Feng, Zhendong; Cai, Zhigang; Zhang, Lihe; Zhou, Demin

    2015-01-01

    To elucidate the genetic effect involved in the premalignant progression of chronic inflammation to cancer, we performed microRNA and mRNA profiling in oral lichen planus (OLP), oral squamous cell carcinoma (OSCC), and normal tissue from the same patients. We demonstrate the involvement of a suppressive microRNA, miR-375, in the regulation of this premalignant progression via KLF5, a transcription factor that modulates the expression of genes contributing to proliferation and apoptosis. We found that miR-375 abundance decreased in tissues with progression from the normal state to OLP and subsequently to OSCC. Restoration of miR-375 by transduction of a synthetic mimic into OSCC cells repressed cellular proliferation and promoted apoptosis, with concomitant down-regulation of KLF5, and vice versa. The direct binding of miR-375 to the 3′-untranslated region of KLF5 was further confirmed. Additionally, Survivin (BIRC5), a target of KLF5, was also regulated by miR-375, explaining the susceptibility of miR-375-mimic transfected cells to apoptosis. Further analysis of clinical specimens suggested that expression of KLF5 and BIRC5 is up-regulated during the progression from inflammation to cancer. Our findings provide novel insights into the involvement of microRNAs in progression of inflammation to carcinoma and suggest a potential early-stage biomarker or therapy target for oral carcinoma. PMID:26474386

  11. Rheumatic Diseases and Malignancies

    PubMed Central

    BOJINCA, Violeta; JANTA, Iustina

    2012-01-01

    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. PMID:23482881

  12. Urban legends series: oral manifestations of HIV infection.

    PubMed

    Patton, L L; Ramirez-Amador, V; Anaya-Saavedra, G; Nittayananta, W; Carrozzo, M; Ranganathan, K

    2013-09-01

    Human immunodeficiency virus-related oral lesions (HIV-OLs), such as oral candidiasis (OC) and oral hairy leukoplakia (OHL), have been recognized as indicators of immune suppression since the beginning of the global HIV epidemic. The diagnosis and management of HIV disease and spectrum of opportunistic infection has changed over the past 30 years as our understanding of the infection has evolved. We investigated the following controversial topics: (i) Are oral manifestations of HIV still relevant after the introduction of highly active antiretroviral therapy (HAART)? (ii) Can we nowadays still diagnose HIV infection through oral lesions? (iii) Is the actual classification of oral manifestations of HIV adequate or does it need to be reviewed and updated? (iv) Is there any novelty in the treatment of oral manifestations of HIV infection? Results from extensive literature review suggested the following: (i) While HAART has resulted in significant reductions in HIV-OLs, many are still seen in patients with HIV infection, with OC remaining the most common lesion. While the relationship between oral warts and the immune reconstitution inflammatory syndrome is less clear, the malignant potential of oral human papillomavirus infection is gaining increasing attention. (ii) Effective antiretroviral therapy has transformed HIV from a fatal illness to a chronic manageable condition and as a result expanded screening policies for HIV are being advocated both in developed and in developing countries. Affordable, reliable, and easy-to-use diagnostic techniques have been recently introduced likely restricting the importance of HIV-OLs in diagnosis. (iii) The 1993 EC-Clearinghouse classification of HIV-OLs is still globally used despite controversy on the relevance of periodontal diseases today. HIV-OL case definitions were updated in 2009 to facilitate the accuracy of HIV-OL diagnoses by non-dental healthcare workers in large-scale epidemiologic studies and clinical trials. (iv

  13. The Cultivable Human Oral Gluten-Degrading Microbiome and its Potential Implications in Celiac Disease and Gluten Sensitivity

    PubMed Central

    Fernandez-Feo, Martin; Wei, Guoxian; Blumenkranz, Gabriel; Dewhirst, Floyd E.; Schuppan, Detlef; Oppenheim, Frank G.; Helmerhorst, Eva J.

    2013-01-01

    Celiac disease is characterized by intestinal inflammation caused by gluten, proteins which are widely contained in the Western diet. Mammalian digestive enzymes are only partly capable of cleaving gluten, and fragments remain that induce toxic responses in celiac patients. We found that the oral microbiome is a novel and rich source of gluten degrading enzymes. Here we report on the isolation and characterization of the cultivable resident oral microbes that are capable of cleaving gluten, with special emphasis on its immunogenic domains. Bacteria were obtained by a selective culturing approach and enzyme activities were characterised by: 1) Hydrolysis of paranitroanilide-derivatised gliadin-derived tripeptide substrates; 2) Gliadin degradation in-gel (gliadin zymography); 3) Gliadin degradation in solution; 4) Proteolysis of the highly immunogenic α-gliadin-derived 33-mer. For select strains pH activity profiles were determined. The culturing strategy yielded 87 aerobic and 63 anaerobic strains. Species with activity in at least two of the four assays were typed as: Rothia mucilaginosa HOT-681, Rothia aeria HOT-188, Actinomyces odontolyticus HOT-701, Streptococcus mitis HOT-677, Streptococcus sp. HOT-071, Neisseria mucosa HOT-682 and Capnocytophaga sputigena HOT-775, with Rothia species being active in all four assays. Cleavage specificities and substrate preferences differed among the strains identified. The approximate molecular weights of the enzymes were ~75 kD (Rothia spp.), ~60 kD (A. odontolyticus) and ~150 kD (Streptococcus spp.). In conclusion, this study identified new gluten-degrading microorganisms in the upper gastro-intestinal tract. A cocktail of the most active oral bacteria, or their isolated enzymes, may offer promising new treatment modalities for celiac disease. PMID:23714165

  14. ASK1 (MAP3K5) as a potential therapeutic target in malignant fibrous histiocytomas with 12q14-q15 and 6q23 amplifications.

    PubMed

    Chibon, Frédéric; Mariani, Odette; Derré, Josette; Mairal, Aline; Coindre, Jean-Michel; Guillou, Louis; Sastre, Xavier; Pédeutour, Florence; Aurias, Alain

    2004-05-01

    Malignant fibrous histiocytomas (MFHs) are aggressive tumors without any definable line of differentiation. We recently demonstrated that about 20% of them are characterized by high-level amplifications of the 12q14-q15 chromosome region, associated with either 1p32 or 6q23 band amplification. This genetic finding, very similar to that in well-differentiated liposarcomas, strongly suggests that these tumors actually correspond to undifferentiated liposarcomas. It also suggests that the lack of differentiation could be the consequence of amplification of target genes localized in the 1p32 or 6q23 bands. We report here the characterization by array CGH of the 6q23 minimal region of amplification. Our findings demonstrate that amplification and overexpression of ASK1 (MAP3K5), a gene localized in the 6q23 band and encoding a mitogen-activated protein kinase kinase kinase of the JNK-MAPK signaling pathway, could inhibit the adipocytic differentiation process of the tumor cells. Treatment of a cell line with specific inhibitors of ASK1 protein resulted in the bypass of the differentiation block and induction of a strong adipocytic differentiation. These observations indicate that ASK1 is a target for new therapeutic management of these aggressive tumors. PMID:15034865

  15. In vitro Evaluation of Copaifera oblongifolia Oleoresin Against Bacteria Causing Oral Infections and Assessment of Its Cytotoxic Potential.

    PubMed

    da S Moraes, Thaís; Leandro, Luis F; de O Silva, Larissa; Santiago, Mariana B; Souza, Ariana B; Furtado, Ricardo A; Tavares, Denise C; Veneziani, Rodrigo C S; Ambrósio, Sérgio R; Bastos, Jairo K; Martins, Carlos H G

    2016-01-01

    The oral cavity, which harbors more than 750 bacterial species, is one of the most diverse sites of the human body. Some of these bacteria have been associated with oral diseases, such as dental caries and endodontic infections. We report on the antimicrobial and cytotoxic activities of Copaifera oblongifolia oleoresin against bacteria that cause caries and endodontic infections. The aim of this study is to determine the minimum (MIC) and the bactericidal (MBC) inhibitory concentrations as well as the biofilm inhibition ability (through determination of MBIC50) of the C. oblongifolia oleoresin. This study also investigated the bactericidal kinetics (time-kill curves) and the synergistic effect of the C. oblongifolia oleoresin. Additionally, this study evaluated the cytotoxic activity of the oleoresin toward V79 cells by means of the colony-forming assay. The C. oblongifolia oleoresin gave promising MIC and MBC values, which ranged from 25 to 200 μg/mL. Analysis of the MBIC50values of the oleoresin revealed it displayed biofilm inhibitory activity against all the assayed bacteria. Analysis of the bactericidal kinetics showed different behaviors of the oleoresin against the tested bacteria at the different time intervals and concentrations assayed in this study. An additive effect of the oleoresin with chlorhexidine dihydrochloride occurred only for S. mitis and A. actinomycetemcomitans. The C. oblongifolia oleoresin showed cytotoxic activity at concentrations ≥ 625 μg/mL.

  16. Cutaneous malignancies in immunosuppressed organ transplant recipients.

    PubMed

    Seda, Ivette M Sosa; Zubair, Adeel; Brewer, Jerry D

    2014-01-01

    During the past century, organ transplantation has delivered the miracle of life to more than 500,000 patients in need. Secondary malignancies have developed as an unforeseen consequence of intense immunosuppressive regimens. Cutaneous malignancies have been recognized as the most frequent cancer that arises post-transplantation. Among organ transplant recipients (OTRs), skin cancer is a substantial cause of morbidity and potential mortality. The authors discuss epidemiology and clinical presentation of cutaneous malignancies; associated risk factors; recommendation for the care of immunosuppressed OTRs, and emerging therapies on the horizon.

  17. Twice malignant transformation of hypertrophic lichen planus.

    PubMed

    Krasowska, Dorota; Kozłowicz, Katarzyna; Kowal, Małgorzata; Kurylcio, Andrzej; Budzyńska-Włodarczyk, Jolanta; Polkowski, Wojciech; Chodorowska, Grażyna

    2012-01-01

    Lichen planus is a chronic mucocutaneous T-cell-mediated disease, the cause of which remains unknown. The first case of lichen planus that transformed into squamous cell carcinoma was reported in 1903. The presented study concerns the case of a 62-year-old woman in whom twice malignant transformation of hypertrophic lichen planus in the dorsal part of the left foot developed. Several studies have pointed out the malignant transformation potential of lichen planus. Epidemiological studies from the last 20 years have revealed a malignant transformation rate of 0.27% per year, emphasizing the importance of the clinical follow-up of lichen planus patients.

  18. Dental status, dental rehabilitation procedures, demographic and oncological data as potential risk factors for infected osteoradionecrosis of the lower jaw after radiotherapy for oral neoplasms: a retrospective evaluation

    PubMed Central

    2013-01-01

    Purpose Retrospective evaluation of the dental status of patients with oral cancer before radiotherapy, the extent of dental rehabilitation procedures, demographic and radiotherapy data as potential risk factors for development of infected osteoradionecrosis of the lower jaw. Methods A total of 90 patients who had undergone radiotherapy for oral cancer were included into this retrospective evaluation. None of them had distant metastases. After tumour surgery the patients were referred to an oral and maxillofacial surgeon for dental examination and the necessary dental rehabilitation procedures inclusive potential tooth extraction combined with primary soft tissue closure. Adjuvant radiotherapy was started after complete healing of the gingiva (> 7 days after potential extraction). The majority of patients (n = 74) was treated with conventionally fractionated radiotherapy with total doses ranging from 50-70Gy whereas further 16 patients received hyperfractionated radiotherapy up to 72Gy. The records of the clinical data were reviewed. Furthermore, questionnaires were mailed to the patients’ general practitioners and dentists in order to get more data concerning tumour status and osteoradionecrosis during follow-up. Results The patients’ dental status before radiotherapy was generally poor. On average 10 teeth were present, six of them were regarded to remain conservable. Extensive dental rehabilitation procedures included a mean of 3.7 tooth extractions. Chronic periodontitis with severe attachment loss was found in 40%, dental biofilm in 56%. An infected osteoradionecrosis (IORN) grade II according to (Schwartz et al., Am J Clin Oncol 25:168-171, 2002) was diagnosed in 11 of the 90 patients (12%), mostly within the first 4 years after radiotherapy. We could not find significant prognostic factors for the occurrence of IORN, but a trendwise correlation with impaired dental status, rehabilitation procedures, fraction size and tumour outcome. Conclusion The

  19. Dual inhibition of angiotensin-converting enzyme and neutral endopeptidase by the orally active inhibitor mixanpril: a potential therapeutic approach in hypertension.

    PubMed Central

    Fournié-Zaluski, M C; Gonzalez, W; Turcaud, S; Pham, I; Roques, B P; Michel, J B

    1994-01-01

    In the treatment of cardiovascular disease, it could be of therapeutic interest to associate the hypotensive effects due to the inhibition of angiotensin II formation with the diuretic and natriuretic responses induced by the protection of the endogenous atrial natriuretic peptide (ANP). Investigation of this hypothesis requires an orally active compound able to simultaneously inhibit angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), which is involved in renal ANP metabolism. Such compounds have been rationally designed by taking into account the structural characteristics of the active site of both peptidases. Among them, RB 105, N-[(2S,3R)-2-mercaptomethyl-1-oxo-3-phenylbutyl]-(S)-alanine, inhibited NEP and ACE with Ki values of 1.7 +/- 0.3 nM and 4.2 +/- 0.5 nM, respectively. Intravenous infusion of RB 105 in conscious spontaneously hypertensive rats prevented the pressor response to exogenous angiotensin I and potentiated the natriuretic response to ANP. Infusion of RB 105, at 2.5, 5, 10, 25, and 50 mg/kg per hr decreased blood pressure dose-dependently in conscious catheterized spontaneously hypertensive rats and increased diuresis and natriuresis. Infusion of RB 105 as a bolus of 25 mg/kg followed by 25 mg/kg per hr similarly decreased blood pressure and increased natriuresis in three different models of hypertension (renovascular, deoxycorticosterone acetate-salt, and spontaneously hypertensive rats). Mixanpril, a lipophilic prodrug of RB 105 (ED50 values when given orally to mice, 0.7 mg/kg for NEP; 7 mg/kg for ACE), elicited dose-dependent hypotensive effects of long duration in spontaneously hypertensive rats after oral administration [-37 mmHg for 50 mg/kg twice a day (1 mmHg = 133 Pa) and is therefore the first dual NEP/ACE inhibitor potentially useful for clinical investigations. Images PMID:8171037

  20. Distinct clinicopathological features of NAB2-STAT6 fusion gene variants in solitary fibrous tumor with emphasis on the acquisition of highly malignant potential.

    PubMed

    Akaike, Keisuke; Kurisaki-Arakawa, Aiko; Hara, Kieko; Suehara, Yoshiyuki; Takagi, Tatsuya; Mitani, Keiko; Kaneko, Kazuo; Yao, Takashi; Saito, Tsuyoshi

    2015-03-01

    The impact of NGFI-A binding protein 2 (NAB2)-signal transducer and activator of transcription 6 (STAT6) fusion on the biological behavior and the mechanism of acquisition of malignant phenotype in solitary fibrous tumor (SFT) is not well understood. We examined variations of the NAB2-STAT6 fusion gene in 40 cases of SFT using formalin-fixed, paraffin-embedded tissues and secondary genetic alterations of tumor protein p53 (TP53),, platelet-derived growth factor receptor, β polypeptide (PDGFRB), and telomerase reverse transcriptase (TERT) promoters. These gene variations were compared with the clinicopathological features. The 2-year and 5-year disease-free survival rates (DFSRs) were 91% and 83%, respectively. All 40 samples demonstrated nuclear staining for STAT6, including CD34-negative cases. Moreover, p53-positive staining was associated with a lower DFSR and was significantly associated with higher Ki-67 label index, higher mitotic rate (mitosis, >4/high-power field), and the presence of nuclear atypia/pleomorphism. NAB2-STAT6 fusions were detected in all of the cases; the NAB2 exon 4-STAT6 exon 2, the most common genotype, appeared in 18 cases, which was associated with thoracic tumor location and the less aggressive phenotype. In contrast, tumors with NAB2 exon 6-STAT6 exon 16/18 demonstrated an aggressive phenotype. Mutations in TP53 and PDGFRB were detected in 2 and 3 cases respectively, and these occurred in a mutually exclusive fashion. TERT promoter hot spot mutations were observed in 5 cases, which were associated with shorter DFSR. Two dedifferentiated SFT cases harbored both TP53 and TERT promoter mutations. TP53 mutations, which result in its overexpression, in combination with TERT promoter mutations seem to play an important role in the dedifferentiation process.

  1. Healing Potentials of Oral Moringa Oleifera Leaves Extract and Tetracycline on Methicillin Resistant Staphylococcus Aureus Infected Wounds of Wistar rats.

    PubMed

    Eyarefe, Oghenemega D; Idowu, Aderayo; Afolabi, Jeremiah M

    2015-01-01

    The effects of oral dose of aqueous extract of Moringa oleifera and tetracycline antibiotics on cutaneous wounds infected with Staphylococcus aureus were studied in eighteen adult wistar rats (159±31.5g) randomized into three groups: Group A, n = 6, Moringa oleifera-(300 mg/kg). Group B, n = 6, tetracycline (9.4 mg/kg) and Group C, n = 6, Sterile water (control). Six millimetres diameter nape wound, created on each rat under 2% xylazine (5 mg/kg) and 5% ketamine (35 mg/kg), was contaminated with Staphylococcus aureus (108 Colony Forming Unit (CFU). Following infection, treatment was commenced with daily oral dose of test preparations and the wounds were evaluated every other day i.e., day 3, 5, 7, 9, 11, 13 and 15 for wetness (wound exudation), wound edge oedema, hyperaemia, granulation tissues and contraction (diameter). Severe wound exudation existed in all the groups between days 0-3 (p = 1.00). A significantly less wound exudation was observed at days 3-5 (p = 0.000) and 5-9 (p = 0.003) (Control< Tetracycline Moringa> Tetracycline). Differences in wound diameter was not significant except at days 5-9 (p = 0.013) (Control> Moringa >Tetracycline). Oral doses of Moringa oleifera extract (300mg/kg) and tetracycline (9.4mg/kg) are not effective as antimicrobial or immune-boosting agents to enhance healing of wounds infected with Staphylococcus aureus and hence not recommended for rapid clearance of Staphylococcus aureus infected wounds.

  2. Comparison of oral treatment of uncomplicated urogenital and rectal gonorrhoea with cefuroxime axetil ester or clavulanic acid potentiated amoxycillin (Augmentin).

    PubMed Central

    Schift, R; van Ulsen, J; Ansink-Schipper, M C; van Joost, T; Michel, M F; Woudstra, R K; Stolz, E

    1986-01-01

    In a randomised study of two drugs for the oral treatment of uncomplicated urogenital and rectal gonorrhoea the therapeutic effect of cefuroxime axetil ester (CAE) and amoxycillin plus clavulanic acid (A + C) was compared. Cefuroxime axetil ester 1.5 g was given to 129 men and 118 women. Amoxycillin 3.0 g and clavulanic acid 0.25 g was given to 131 men and 122 women. Both treatments were combined with probenecid 1.0 g and administered in a single oral dose. Of the 500 patients thus treated, 376 were assessable. In the group taking CAE, failure rates were 0.9% for the men and 0% for the women; and the overall failure rate was 0.5%. In the group taking A + C the equivalent failure rates were 4.6%, 1.2%, and 3.1%. The differences were not significant. Penicillinase producing Neisseria gonorrhoeae (PPNG) was isolated from 5.6% of the assessable patients. All 10 PPNG infections in the group taking CAE and four of 11 PPNG infections in the group taking A + C were cured. These numbers were too small to draw a definite conclusion about the efficacy of both drugs in this type of infection. Postgonococcal urethritis was observed in 35% of the men in the group taking CAE and in 32% of those in the group taking A + C. Side effects were noted in 38% of the group taking CAE and 28% of the group taking A + C. Nausea and vomiting were more commonly observed in the group taking CAE; and diarrhoea was more commonly observed in the group taking A + C. PMID:3533755

  3. Nutritional Aspects of Essential Trace Elements in Oral Health and Disease: An Extensive Review.

    PubMed

    Bhattacharya, Preeti Tomar; Misra, Satya Ranjan; Hussain, Mohsina

    2016-01-01

    Human body requires certain essential elements in small quantities and their absence or excess may result in severe malfunctioning of the body and even death in extreme cases because these essential trace elements directly influence the metabolic and physiologic processes of the organism. Rapid urbanization and economic development have resulted in drastic changes in diets with developing preference towards refined diet and nutritionally deprived junk food. Poor nutrition can lead to reduced immunity, augmented vulnerability to various oral and systemic diseases, impaired physical and mental growth, and reduced efficiency. Diet and nutrition affect oral health in a variety of ways with influence on craniofacial development and growth and maintenance of dental and oral soft tissues. Oral potentially malignant disorders (OPMD) are treated with antioxidants containing essential trace elements like selenium but even increased dietary intake of trace elements like copper could lead to oral submucous fibrosis. The deficiency or excess of other trace elements like iodine, iron, zinc, and so forth has a profound effect on the body and such conditions are often diagnosed through their early oral manifestations. This review appraises the biological functions of significant trace elements and their role in preservation of oral health and progression of various oral diseases. PMID:27433374

  4. Nutritional Aspects of Essential Trace Elements in Oral Health and Disease: An Extensive Review

    PubMed Central

    Hussain, Mohsina

    2016-01-01

    Human body requires certain essential elements in small quantities and their absence or excess may result in severe malfunctioning of the body and even death in extreme cases because these essential trace elements directly influence the metabolic and physiologic processes of the organism. Rapid urbanization and economic development have resulted in drastic changes in diets with developing preference towards refined diet and nutritionally deprived junk food. Poor nutrition can lead to reduced immunity, augmented vulnerability to various oral and systemic diseases, impaired physical and mental growth, and reduced efficiency. Diet and nutrition affect oral health in a variety of ways with influence on craniofacial development and growth and maintenance of dental and oral soft tissues. Oral potentially malignant disorders (OPMD) are treated with antioxidants containing essential trace elements like selenium but even increased dietary intake of trace elements like copper could lead to oral submucous fibrosis. The deficiency or excess of other trace elements like iodine, iron, zinc, and so forth has a profound effect on the body and such conditions are often diagnosed through their early oral manifestations. This review appraises the biological functions of significant trace elements and their role in preservation of oral health and progression of various oral diseases. PMID:27433374

  5. Drugs Approved for Malignant Mesothelioma

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Malignant Mesothelioma This page lists cancer ... in malignant mesothelioma that are not listed here. Drugs Approved for Malignant Mesothelioma Alimta (Pemetrexed Disodium) Pemetrexed ...

  6. Investigation of the oral infections and manifestations seen in patients with advanced cancer

    PubMed Central

    Xu, Lihua; Zhang, Hualin; Liu, Jinsong; Chen, Xiaowei

    2013-01-01

    Objective: A prospective, observational study was undertaken to investigate the epidemiology of oral infection among the patients with advanced malignancies, and to investigate the effects of therapy strategies and risk factors on the incidence of oral infection. Methods: The patients with advanced malignancies were enrolled into the study. The incidence of oral infection with different malignant tumor groups or different treatment methods and the diagnoses of oral infection were confirmed. Demographic data on age, gender, bed rest time, nutritional status, smoking habit and the presence of oral prosthesis were also recorded. Results: Oral infection was prevalent in 46% (391/850) of all cancer patients, with the highest rate in oral and maxillofacial cancer group (67%), followed by Hematological malignancy group (58.6%) and other groups (ranging from 43.3% to 35.3%). Oral candidiasis, oral herpes simplex, and oral mucositis were the popular infectious diseases in the patients. Chemotherapy and radiotherapy, especially combined radio- and chemotherapy, resulted in more oral infections compared with palliative care and surgery. Poor nutritional status and oral prosthesis were identified as independent risk factors associated with oral infection. Conclusion: Oral infection is prevalent among advanced cancer patients and associated with therapy methods and risk factors. More oral health care should be carried out for the patients with advanced malignant tumor. PMID:24353702

  7. Oral nicotinamide and actinic keratosis: a supplement success story.

    PubMed

    Kim, Burcu; Halliday, Gary M; Damian, Diona L

    2015-01-01

    Nicotinamide has shown potential as a safe and effective intervention for the prevention of malignant and premalignant skin lesions. Recent studies have shown that nicotinamide, in both oral and topical forms, is able to prevent ultraviolet-induced immunosuppression in humans [1,2,3] and mice [4,5]. Immunosuppression is a known factor for the progression of premalignant lesions, such as actinic keratosis [6]. Murine studies have shown that nicotinamide is also able to protect against photocarcinogenesis [4,5]. Preliminary human studies suggest that nicotinamide may help prevent skin cancers and enhance the regression of actinic keratoses.

  8. Oral nicotinamide and actinic keratosis: a supplement success story.

    PubMed

    Kim, Burcu; Halliday, Gary M; Damian, Diona L

    2015-01-01

    Nicotinamide has shown potential as a safe and effective intervention for the prevention of malignant and premalignant skin lesions. Recent studies have shown that nicotinamide, in both oral and topical forms, is able to prevent ultraviolet-induced immunosuppression in humans [1,2,3] and mice [4,5]. Immunosuppression is a known factor for the progression of premalignant lesions, such as actinic keratosis [6]. Murine studies have shown that nicotinamide is also able to protect against photocarcinogenesis [4,5]. Preliminary human studies suggest that nicotinamide may help prevent skin cancers and enhance the regression of actinic keratoses. PMID:25561219

  9. Management of Inoperable Malignant Neoplasms.

    PubMed

    Kiess, Ana P; Quon, Harry

    2016-01-01

    For patients with inoperable salivary gland malignancy, radiation therapy has significant limitations but has been the mainstay of treatment. With standard photon radiation (X-rays), the 10-year loco-regional control (LRC) and overall survival rates are only ∼25%. Neutron radiation has potential biological advantages over photon radiation because it causes increased DNA damage, and studies of patients with inoperable salivary gland malignancy have shown improved 6-year LRC and overall survival of ∼60%. However, neutron radiation may also increase the risk of late toxicities, especially central nervous system toxicities after treatment of tumors involving the base of the skull. Proton radiation has potential physical advantages due to minimal exit dose through normal tissues, and a recent study has demonstrated 90% 5-year LRC after combined proton/photon radiation for adenoid cystic carcinoma involving the base of the skull. Stereotactic radiosurgery has also been used in combination with neutrons or standard photons as a technique to boost the skull base. The use of concurrent chemotherapy as a radiosensitizer has been considered based on extrapolation of data on squamous cell carcinomas, but further data are needed on inoperable salivary gland malignancies. Newer targeted therapies are also under investigation, and clinical trial enrollment is encouraged. PMID:27093559

  10. Understanding Carcinogenesis for Fighting Oral Cancer

    PubMed Central

    Tanaka, Takuji; Ishigamori, Rikako

    2011-01-01

    Oral cancer is one of the major global threats to public health. Oral cancer development 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 able to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will give us important advances for detecting high-risk patients, monitoring preventive interventions, assessing cancer risk, and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from research using appropriate animal carcinogenesis models. New approaches, such as interventions with molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy. PMID:21772845

  11. Solitary fibrous tumor of the oral cavity with a predominant leiomyomatous-like pattern: A potential diagnostic pitfall.

    PubMed

    Amico, Paolo; Colella, Giuseppe; Rossiello, Raffaele; Maria Vecchio, Giada; Leocata, Pietro; Magro, Gaetano

    2010-07-15

    The diagnosis of solitary fibrous tumor (SFT) is usually straightforward if the typical morphologic features, including a wide variety of growth patterns, are identified. We report the clinical, radiologic, and pathologic findings of a rare case of intraoral SFT which exhibited a predominant leiomyomatous-like appearance, closely reminiscent of a leiomyoma, at both incisional and excisional biopsy. Histologically, the tumor was composed predominantly of intersecting fascicles of eosinophilic spindle-shaped cells, variably set in a fibrous stroma. A focal hemangiopericytoma-like growth pattern with alternating hypercellular and hypocellular areas, as well as the deposition of dense keloid-type collagen, raising the suspicion of SFT, could be identified only after a careful examination of the whole tumor. Immunohistochemistry was helpful in confirming the diagnosis of SFT, revealing a diffuse staining of neoplastic cells for vimentin, CD34, bcl-2 protein, and, focally, CD99. Myogenic markers (alpha-smooth muscle actin, desmin, h-caldesmon) were not expressed. The pathologist should be aware of this variant of intraoral leiomyomatous-like SFT to avoid a misdiagnosis of leiomyoma. The distinction of SFT from leiomyoma in the oral cavity is important to assure both correct treatment and prognostic information.

  12. Oral leukoplakia, the ongoing discussion on definition and terminology

    PubMed Central

    2015-01-01

    In the past decades several definitions of oral leukoplakia have been proposed, the last one, being authorized by the World Health Organization (WHO), dating from 2005. In the present treatise an adjustment of that definition and the 1978 WHO definition is suggested, being : “A predominantly white patch or plaque that cannot be characterized clinically or pathologically as any other disorder; oral leukoplakia carries an increased risk of cancer development either in or close to the area of the leukoplakia or elsewhere in the oral cavity or the head-and-neck region”. Furthermore, the use of strict diagnostic criteria is recommended for predominantly white lesions for which a causative factor has been identified, e.g. smokers’ lesion, frictional lesion and dental restoration associated lesion. A final diagnosis of such leukoplakic lesions can only be made in retrospect after successful elimination of the causative factor within a somewhat arbitrarily chosen period of 4-8 weeks. It seems questionable to exclude “frictional keratosis” and “alveolar ridge keratosis” from the category of leukoplakia as has been suggested in the literature. Finally, brief attention has been paid to some histopathological issues that may cause confusion in establishing a final diagnosis of leukoplakia. Key words:Oral leukoplakia, potentially malignant oral disorders, definition. PMID:26449439

  13. Immunohistochemical Evaluation of Mast Cells in Leukoplakia and Oral Squamous Cell Carcinoma

    PubMed Central

    Narasimhan, Malathi

    2016-01-01

    Introduction More than 90% of oral cancers are squamous cell carcinomas with oral leukoplakia being the most common potentially malignant disorder. Among the cell types in the stroma, mast cells play an important role in tumourigenesis through various mechanisms. Aim The present study was aimed at comparing the mast cell count among normal oral mucosa, leukoplakia and Oral squamous cell carcinoma (OSSC) and to evaluate the possible role of mast cells in carcinogenesis. Materials and Methods Mast cell count was assessed immunohistochemically using anti-mast cell tryptase amongst 20 cases of leukoplakia and OSSC each and 10 normal gingival samples. Overall comparison was done using Kruskal Wallis test and intergroup comparison was done using Mann-Whitney U test. Results The results of the present study showed an increase in mast cell count from normal oral mucosa (Mean: 7.73) to leukoplakia (Mean: 15.11) to squamous cell carcinoma (Mean: 22.73). Comparison of mean number of mast cells amongst three groups (p-value: 0.001) and intergroup comparisons showed statistical significance. Conclusion Mast cells favour malignant transformation and can be used as indicators of disease progression. PMID:27656549

  14. Transplantation-Associated Long-Term Immunosuppression Promotes Oral Colonization by Potentially Opportunistic Pathogens without Impacting Other Members of the Salivary Bacteriome

    PubMed Central

    Hong, Bo-Young; Frias-Lopez, Jorge; Dupuy, Amanda K.; Angeloni, Mark; Abusleme, Loreto; Terzi, Evimaria; Ioannidou, Effie; Strausbaugh, Linda D.

    2013-01-01

    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

  15. Oral supplementation of Ocimum basilicum has the potential to improves the locomotory, exploratory, anxiolytic behavior and learning in adult male albino mice.

    PubMed

    Zahra, K; Khan, M A; Iqbal, F

    2015-01-01

    The aim of this project was to determine the effect of 100 mg/ml solvent/kg body weight of Ocimum basilicum leaf extract on neuromuscular co-ordination, exploratory, locomotory and short-term memory formation in male albino mice. Five weeks old, male albino mice were used as the experimental animals in order to demonstrate the effect of O. basilicum's extract on learning and memory. Each male albino mouse was weighted and orally treated either with 100 mg/ml solvent/kg body weight of O. basilicum leaf extract or with commercially available saline solution (Otsuka, Pakistan) for 7 days. Behavioral observations were made by applying a series of neurological tests (Elevated plus maze, Light and dark box, Open field and Rota rod). Dose supplementation continued during neurological testing. It was observed that 100 mg/ml solvent/kg body weight of leaf extract improves neuromuscular co-ordination and male albino mouse performance in open field, light dark box and during novel object test when compared with control group. We concluded that 100 mg/ml solvent/kg body weight of leaf extract has the potential to improve neuromuscular co-ordination, exploratory behavior, object recognition ability and transfer latency in male albino mice and can be safely administrated orally.

  16. Panuveal malignant mesenchymoma.

    PubMed

    Pe'er, J; Neudorfer, M; Ron, N; Anteby, I; Lazar, M; Rosenmann, E

    1995-09-01

    Intraocular malignant mesenchymal tumors are very rare, and only a few case reports of such primary and metastatic tumors have been reported. We report a case of a malignant mesenchymoma involving the entire uveal tract. A 21-year-old woman presented with a tumor on the whole iris of the right eye, which caused intractable glaucoma. Upon enucleation of the eye, a very anaplastic tumor was found to occupy the whole uveal tract; its features were compatible with a tumor of mesenchymal origin, including rhabdomyosarcomatous and liposarcomatous characteristics. Choroidal osteoma was a coincidental finding. The histologic findings of the tumor were of two types of malignant mesenchymal tumors, and therefore the diagnosis of malignant mesenchymoma was made. This is to our knowledge the first tumor of its kind to be reported intraocularly. PMID:7668945

  17. The Malignant Protein Puzzle.

    PubMed

    Walker, Lary C; Jucker, Mathias

    2016-01-01

    When most people hear the words malignant and brain, cancer immediately comes to mind. But our authors argue that proteins can be malignant too, and can spread harmfully through the brain in neurodegenerative diseases that include Alzheimer's, Parkinson's, CTE, and ALS. Studying how proteins such as PrP, amyloid beta, tau, and others aggregate and spread, and kill brain cells, represents a crucial new frontier in neuroscience. PMID:27408676

  18. Human papillomavirus infection of the oral mucosa.

    PubMed

    Garlick, J A; Taichman, L B

    1991-08-01

    This article reviews the lesions of oral mucosa that contain human papillomavirus (HPV). These HPV-associated lesions can be classified into two broad types on the basis of their biologic behavior, benign lesions and premalignant malignant or malignant lesions. Benign oral lesions include squamous cell papilloma (SCP), verruca vulgaris (VV), condyloma acuminatum (CA), and focal epithelial hyperplasia (FEH). Of these entities, VV, CA, and FEH demonstrate characteristic HPV-induced cytopathic effects, whereas SCP infrequently shows such changes. All of these lesions show a clear association with HPV. Premalignant and malignant oral lesions include leukoplakia and squamous cell carcinoma. The etiologic role of HPV in these lesions is still unclear. Koilocytosis is the most common cytopathic effect seen in both groups of lesions. Even though it is sometimes difficult to distinguish between hyperplastic lesions such as SCP, VV, and CA, clinical and certain histologic features can facilitate the diagnosis. Although exceptions do exist, each of the two classes of lesions is most commonly associated with particular HPV types. The benign oral lesions are associated with HPV 2, 4, 6, 11, 13, and 32; the malignant oral lesions are associated with HPV 16 and 18. No preferential association has been demonstrated between specific HPV types and a particular oral lesion.

  19. [Oral ulcers].

    PubMed

    Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

    2005-10-29

    Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology. PMID:16277953

  20. [Oral ulcers].

    PubMed

    Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

    2005-10-29

    Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology.

  1. Targeting the S1 and S3 subsite of trypsin with unnatural cationic amino acids generates antimicrobial peptides with potential for oral administration.

    PubMed

    Karstad, Rasmus; Isaksen, Geir; Wynendaele, Evelien; Guttormsen, Yngve; De Spiegeleer, Bart; Brandsdal, Bjørn-Olav; Svendsen, John Sigurd; Svenson, Johan

    2012-07-26

    This study investigates how the S1 and S3 site of trypsin can be challenged with cationic amino acid analogues to yield active antimicrobial peptides with stability toward tryptic degradation. It is shown that unnatural analogues can be incorporated to generate stable peptides with maintained bioactivity to allow for a potential oral uptake. Selected peptides were studied using isothermal calorimetry and computational methods. Both stable and unstable peptides were found to bind stoichiometrically to trypsin with dissociation constants ranging 2-60 μM, suggesting several different binding modes. The stability of selected peptides was analyzed in whole organ extracts and the incorporation of homoarginine and 2-amino-(3-guanidino)propanoic acid resulted in a 14- and 50-fold increase in duodenal stability. In addition, a 40- and 70-fold increase in stomach stability is also reported. Overall, these results illustrate how the incorporation of cationic side chains can be employed to generate bioactive peptides with significant systemic stability.

  2. Expression of human telomerase reverse transcriptase protein in oral epithelial dysplasia and oral squamous cell carcinoma: An immunohistochemical study

    PubMed Central

    Raghunandan, Bangalore Nagarajachar; Sanjai, Karpagaselvi; Kumaraswamy, Jayalakshmi; Papaiah, Lokesh; Pandey, Bhavna; Jyothi, Bellur MadhavaRao

    2016-01-01

    compared using analysis of variance (ANOVA). A P < 0.05 was considered to be statistically significant. Results: The mean hTERT positive cells in the study groups were as follows, 62.91% in normal oral mucosa samples, 77.06% in oral epithelial dysplasia cases, and 81.48% in OSCC. In 61.9% of oral epithelial dysplasia and 65% of OSCC in our study, staining was visualized within the nucleus predominantly in the dot like pattern. There was a statistically significant difference in the nature of nuclear stain between oral epithelial dysplasia and OSCC (P = 0.023). Conclusions: Our results suggests that the mean percentage of cells showing hTERT expression steadily increased from normal oral mucosa to oral epithelial dysplasia to OSCC. The steady trend of increase in the percentage of cells was evident in different grades of oral epithelial dysplasia group and OSCC. The nature of hTERT staining did show variations among the three groups and promise to be a potential surrogate marker for malignant transformation. Further studies using IHC on larger sample size and clinical follow-up of these patients will be ascertaining the full potential of hTERT as a surrogate marker of epithelial transformation. PMID:27194869

  3. Thalidomide: an emerging drug in oral mucosal lesions.

    PubMed

    Mubeen, K; Siddiq, M Ahmed; Jigna, V R

    2009-06-01

    Thalidomide has reemerged as a potential drug with new found uses despite its history of having caused devastating congenital birth defects. The drug has become the subject of major interest because of its clinical value in certain clearly defined disorders. Interest in thalidomide was initially rekindled in the mid-1960s by its remarkable effect in lessening the complication of leprosy called erythema nodosum leprosum. Several studies thereafter have demonstrated the use of thalidomide as a wonder drug. However, it was only in July 1998 that the US Food and Drug Administration granted approval for the use of thalidomide under strict patient guidelines. Its apparent immunomodulatory and anti-inflammatory properties led to widespread application in clinical practice. Thalidomide has gained respectability as a promising new drug in oral mucosal lesions. Studies have suggested that thalidomide is effective in severe aphthous stomatitis, Behçet's syndrome, certain oral manifestations of human immunodeficiency virus (HIV) infection, erosive lichen planus, and possibly malignancies.

  4. Prospective Study of Dental Intervention for Hematopoietic Malignancy

    PubMed Central

    Tsuji, K.; Akashi, M.; Furudoi, S.; Yakushijin, K.; Kawamoto, S.; Okamura, A.; Matsuoka, H.; Komori, T.

    2015-01-01

    Various chemotherapeutic agents used in patients with hematopoietic malignancy cause serious side effects, including myelosuppression and immunosuppression. Immunosuppression makes patients more susceptible to infection, resulting in an increased risk of infectious complications, including the development of severe septicemia that may be life-threatening. It is necessary for dental staff to be familiar with an appropriate protocol in such cases and to share information about the chemotherapy with a hematologist. To verify the effectiveness of our dental intervention protocol, we conducted a prospective study on the incidence of complications for each myelosuppressive grade of chemotherapy in patients with hematopoietic malignancy. We compared the incidence of complications between treatment P (patients who finished all the dental treatments according to the protocol) and treatment Q (patients who did not) per grade (A, B, C, D) and incidence of systemic or oral findings. We also compared the incidence of oral complication related to the residual teeth between first chemo (patients who were undergoing chemotherapy for the first time) and prior chemo (not the first time). There were significant differences in inflammatory complications between treatment P and treatment Q. We found that both systemic and oral inflammatory complications increased with higher-grade myelosuppressive chemotherapy. Additionally, there was a significant difference between the incidence of oral complications related to the residual teeth between first chemo and prior chemo. Complete implementation of the dental intervention protocol was associated with fewer oral and systemic infectious and inflammatory complications in patients with hematopoietic malignancies undergoing chemotherapy. The incidence of oral and systemic complications also increased with grade of chemotherapy. These results support the validity of our dental intervention protocol. We should pay close attention to the oral

  5. The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery.

    PubMed

    Ma, Yiming; Fuchs, Adrian V; Boase, Nathan R B; Rolfe, Barbara E; Coombes, Allan G A; Thurecht, Kristofer J

    2015-08-01

    Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan-hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8h to 24h post-administration compared to the free NPs, due to a NP 'guarding' effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems.

  6. Significance of level v lymph node dissection in clinically node positive oral cavity squamous cell carcinoma and evaluation of potential risk factors for level v lymph node metastasis.

    PubMed

    Parikh, Devendra G; Chheda, Yogen P; Shah, Shakuntala V; Patel, Ashok M; Sharma, Mohit R

    2013-09-01

    Level V lymph node (LN) dissection has been significantly associated with postoperative shoulder dysfunction as a sequel of spinal accessory nerve (SAN) dysfunction. The aim of study was to determine the role of level V LN dissection in clinically node positive (cN+) oral cavity cancer. We have prospectively evaluated 210 patients of oral cavity squamous cell carcinoma (SCC). During neck dissection, the contents of the level V LN were dissected, labelled, and processed separately from the neck dissection specimen. We studied the prevalence of histopathologic metastasis to level V nodes in clinically node negative (cN0), cN1 and cN2 groups. Potential risk factors for the involvement of level V LN were also analysed. Of 210 cases, 48 were cN0. Out of them 77 % were pN0 and none of cNo (48) patients had level V metastases. Out of 162 cN+ cases, 112 were cN1 and 49 cN2. Amongst cN1 (112) cases, cN1 with palpable level lb LN (99), 60 % had pN0 and none of them had level V LN involvement but cN1 with palpable ll/lll LN (13), 85 % had pN+ and 1 patient had level V LN involvement (8 %). 8 patients from cN2 (49) group had level V LN involvement (16 %). Over all level V LN involvement was 4.3 %. Tongue was the most common site to give rise to level V LN metastases and extra capsular spread (ECS) was present in 100 % patient with level V LN metastases. Thus, we concluded that, apart from cN0, patients with cN1