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1

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

PubMed Central

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

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

2013-01-01

2

Photodynamic therapy in the management of potentially malignant and malignant oral disorders  

PubMed Central

Photodynamic therapy (PDT) is a minimally-invasive surgical tool successfully targeting premalignant and malignant disorders in the head and neck, gastrointestinal tract, lungs and skin with greatly reduced morbidity and disfigurement. The technique is simple, can commonly be carried out in outpatient clinics, and is highly acceptable to patients. The role of photodynamic therapy in the management of oral potentially malignant disorders and early oral cancer is being discussed.

2012-01-01

3

HBO: A possible supplementary therapy for oral potentially malignant disorders.  

PubMed

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-?, TGF-?, and IFN-?, 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

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

2014-08-01

4

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

PubMed Central

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.

Mortazavi, Hamed; Baharvand, Maryam; Mehdipour, Masoumeh

2014-01-01

5

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

PubMed Central

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

2012-01-01

6

Involvement of potential pathways in malignant transformation from Oral Leukoplakia to Oral Squamous Cell Carcinoma revealed by proteomic analysis  

PubMed Central

Background Oral squamous cell carcinoma (OSCC) is one of the most common forms of cancer associated with the presence of precancerous oral leukoplakia. Given the poor prognosis associated with oral leukoplakia, and the difficulties in distinguishing it from cancer lesions, there is an urgent need to elucidate the molecular determinants and critical signal pathways underlying the malignant transformation of precancerous to cancerous tissue, and thus to identify novel diagnostic and therapeutic target. Results We have utilized two dimensional electrophoresis (2-DE) followed by ESI-Q-TOF-LC-MS/MS to identify proteins differentially expressed in six pairs of oral leukoplakia tissues with dysplasia and oral squamous cancer tissues, each pair was collected from a single patient. Approximately 85 differentially and constantly expressed proteins (> two-fold change, P < 0.05) were identified, including 52 up-regulated and 33 down-regulated. Gene ontological methods were employed to identify the biological processes that were over-represented in this carcinogenic stage. Biological networks were also constructed to reveal the potential links between those protein candidates. Among them, three homologs of proteosome activator PA28 a, b and g were shown to have up-regulated mRNA levels in OSCC cells relative to oral keratinocytes. Conclusion Varying levels of differentially expressed proteins were possibly involved in the malignant transformation of oral leukoplakia. Their expression levels, bioprocess, and interaction networks were analyzed using a bioinformatics approach. This study shows that the three homologs of PA28 may play an important role in malignant transformation and is an example of a systematic biology study, in which functional proteomics were constructed to help to elucidate mechanistic aspects and potential involvement of proteins. Our results provide new insights into the pathogenesis of oral cancer. These differentially expressed proteins may have utility as useful candidate markers of OSCC.

Wang, Zhi; Feng, Xiaodong; Liu, Xinyu; Jiang, Lu; Zeng, Xin; Ji, Ning; Li, Jing; Li, Longjiang; Chen, Qianming

2009-01-01

7

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

Microsoft Academic Search

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

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

2010-01-01

8

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

PubMed

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. PMID:24568491

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

2014-01-01

9

Oral submucous fibrosis--a potentially malignant condition of growing concern.  

PubMed

Oral submucous fibrosis (OSF) is a premalignant condition that primarily affects the oral cavity. The clinical hallmark of this disease is the development of progressive trismus. The latter is a direct consequence of loss of the normal fibro-elasticity of the oral mucosa and replacement of the fibromuscular connective tissue by the deposition of dense collagen. This change in the oral mucosa is aetiologically linked to the areca nut chewing habit where the development of OSF results from the interaction of the mucosa with the chemical constituents of areca. Areca nuts are used as a masticatory substance either alone, in a self-prepared quid or in various commercial preparations known as paan masala and gutka. The habitual usage of these products is rapidly increasing and oral health professionals globally are likely to encounter patients with this disease. The potentially malignant nature of OSF is well documented and habitual areca nut chewing even in the absence of tobacco is an independent risk factor for oral cancer. Public health education against the areca nut chewing habit is essential to eradicate the deleterious effects of this habit on oral health. PMID:23957096

Mahomed, F

2012-11-01

10

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

PubMed Central

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

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

2013-01-01

11

Ex vivo Confocal Imaging with Contrast Agents for the Detection of Oral Potentially Malignant Lesions  

PubMed Central

Objectives We investigated the potential use of real-time confocal microscpy in the non-invasive detection of occult oral potentially malignant lesions. Our objectives were to select the best fluorescence contrast agent for cellular morphology enhancement, to build an atlas of confocal microscopic images of normal human oral mucosa, and to determine the accuracy of confocal microscopy to recognise oral high-grade dysplasia lesions on live human tissue. Materials and Methods Five clinically used fluorescent contrast agents were tested in vitro on cultured human cells and validated ex vivo on human oral mucosa. Images acquired ex vivo from normal and diseased human oral biopsies with bench-top fluorescent confocal microscope were compared to conventional histology. Image analyzer software was used as an adjunct tool to objectively compare high-grade dysplasia versus low-grade dysplasia and normal epithelium. Results Acriflavine Hydrochloride provided the best cellular contrast by preferentially staining the nuclei of the epithelium. Using topical application of Acriflavine Hydrochloride followed by confocal microscopy, we could define morphological characteristics of each cellular layer of the normal human oral mucosa, building an atlas of histology-like images. Applying this technique to diseased oral tissue specimen, we were also able to accurately diagnose the presence of high-grade dysplasia through the increased cellularity and changes in nuclear morphological features. Objective measurement of cellular density by quantitative image analysis was a strong discriminant to differentiate between high-grade dysplasia and low-grade dysplasia lesions. Conclusions Pending clinical investigation, real-time confocal microscopy may become a useful adjunct to detect precancerous lesions that are at high risk of cancer progression, direct biopsy and delineate excision margins.

Hallani, S. El; Poh, C. F.; Macaulay, C. E.; Follen, M.; Guillaud, M.; Lane, P.

2013-01-01

12

Fluorescence spectroscopy for the detection of potentially malignant disorders and squamous cell carcinoma of the oral cavity.  

PubMed

Oral cancer is a public health problem with relevant incidence in the world population. The affected patient usually presents advanced stage disease and the consequence of this delay is a reduction in survival rates. Given this, it is essential to detect oral cancer at early stages. Fluorescence spectroscopy is a non-invasive diagnostic tool that can improve cancer detection in real time. It is a fast and accurate technique, relatively simple, which evaluates the biochemical composition and structure using the tissue fluorescence spectrum as interrogation data. Several studies have positive data regarding the tools for differentiating between normal mucosa and cancer, but the difference between cancer and potentially malignant disorders is not clear. The aim of this study was to evaluate the efficacy of fluorescence spectroscopy in the discrimination of normal oral mucosa, oral cancer, and potentially malignant disorders. The fluorescence spectroscopy was evaluated in 115 individuals, of whom 55 patients presented oral squamous cell carcinoma, 30 volunteers showing normal oral mucosa, and 30 patients having potentially malignant disorders. The spectra were classified and compared to histopathology to evaluate the efficiency in diagnostic discrimination employing fluorescence. In order to classify the spectra, a decision tree algorithm (C4.5) was applied. Despite of the high variance observed in spectral data, the specificity and sensitivity obtained were 93.8% and 88.5%, respectively at 406 nm excitation. These results point to the potential use of fluorescence spectroscopy as an important tool for oral cancer diagnosis and potentially malignant disorders. PMID:24704941

Francisco, Ana Lucia Noronha; Correr, Wagner Rafael; Azevedo, Luciane Hiramatsu; Kern, Vivian Galletta; Pinto, Clóvis Antônio Lopes; Kowalski, Luiz Paulo; Kurachi, Cristina

2014-06-01

13

Malignant transformation of oral lichen planus  

Microsoft Academic Search

Aims: To investigate the malignant potential of oral lichen planus (OLP), a common mucocutaneous disease of unknown aetiology. The malignant potential of OLP is still controversial, with studies reporting malignant transformation rates of between 0 and 5.6%. We also aimed to identify factors that might be associated with malignant transformation. Methods: We retrospectively reviewed the records of 832 patients with

R. Rajentheran; N. R. McLean; C. G. Kelly; M. F. Reed; A. Nolan

1999-01-01

14

Potential of optical coherence tomography for early diagnosis of oral malignancies  

PubMed Central

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.

DeCoro, Michael; Wilder-Smith, Petra

2014-01-01

15

[Squamous cell carcinoma and potentially malignant disorders of the oral mucosa].  

PubMed

Squamous cell carcinoma is the most frequent malignant tumor of the oral mucosa. Various endogenous and exogenous factors promote its development. Therapy and prognosis depend mainly on tumor stage. Early detection is therefore of utmost importance. In most cases cancer develops from "leukoplakia". Both homogeneous leukoplakias as well as "erythroleukoplakias" should be biopsied. The"brush-biopsy", imaging techniques, molecular biologic or DNA tests are not reliable enough at present, often technically demanding and not applicable in daily practice. In extensive lesions "field cancerization" has to be considered. Further important precursor lesions are proliferative verrucous leukoplakia and erosive lichen planus. The management of oral precancerous lesions should be individually tailored: Low-grade dysplasia can be observed. If indicated, patients at risk should be biopsied in intervals. High-grade dysplasia ("carcinoma in situ") should be surgically removed. PMID:19882110

Beck-Mannagetta, J; Hutarew, G

2009-11-01

16

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

PubMed Central

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

2011-01-01

17

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

PubMed

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

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

2012-06-01

18

Histo-blood group ABO antigen in oral potentially malignant lesions and squamous cell carcinoma--genotypic and phenotypic characterization.  

PubMed

Loss of histo-blood group A/B antigens is frequent in oral cancer. It is unclear whether this alteration is due to loss of the chromosomal region encoding the genes. The aim was to investigate genotypic alterations in the ABO locus in oral potentially malignant lesions and carcinomas. Seventy-three cases which expressed A/B antigen in normal epithelium by immunohistochemical (IHC) staining were investigated. Both tumour and normal cells were collected from paraffin-embedded tissue by laser microdissection. DNA was extracted and analysed by PCR coupled with restricted digestion analysis in order to establish the ABO genotype. Total and patchy loss of A/B antigen expression was found in 24/32 carcinomas, 6/7 leukoplakias with severe dysplasia, 12/17 leukoplakias with mild and moderate dysplasia, and 6/17 leukoplakias without dysplasia. Specific A/B allele loss was found in 8/24 cases with carcinoma and 3/24 cases with mild and moderate dysplasia by genotyping analysis. O allele loss was found in 10 cases involving all four groups. In patients with heterozygous genotypes, A/B allelic loss by genotyping analysis was always followed by loss of A/B antigen expression by IHC staining. Loss of A/B antigen expression in tissues which had intact ABO alleles was, however, found and may be explained by other genetic and epigenetic changes. PMID:14961969

Gao, Shan; Bennett, Erik Paul; Reibel, Jesper; Chen, Xinchun; Christensen, Maria Elisabeth; Krogdahl, Annelise; Dabelsteen, Erik

2004-01-01

19

Primary oral malignant melanoma: case report.  

PubMed

Primary oral malignant melanoma usually presents as a dark brown or black lesion. It is a rare malignancy, accounting for less than 1% of all melanomas and 1.6% of all head and neck malignancies, thus forming up to 0.5% of all oral malignancies in the world literature. In general, the prognosis of oral melanoma is poor and worse than that of cutaneous melanoma. The preferred treatment is radical surgery alone or in combination with radiotherapy, chemotherapy, immunotherapy and immunomodulatory agents. A case is presented of a large malignant melanoma of oral cavity, noticed six months before initial biopsy and by history described as a rapidly growing mass. PMID:20635585

Bujas, Tatjana; Pavi?, Ivana; Prus, Andrej; Marusi?, Zlatko; Balicevi?, Drinko

2010-03-01

20

Malignancy Risk Models for Oral Lesions  

PubMed Central

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

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

2013-01-01

21

Effect of topical 5-ALA mediated photodynamic therapy on proliferation index of keratinocytes in 4-NQO-induced potentially malignant oral lesions.  

PubMed

Fractionation can improve photodynamic therapy (PDT) efficacy for potentially malignant oral lesion treatment. The aim of this study was to demonstrate the apoptosis/proliferation index of oral keratinocytes after two sessions of topical 5-ALA-mediated PDT in 4-Nitroquinoline-1-oxide-induced potentially malignant oral lesion, and to suggest the ideal interval between PDT sessions. Immuno-histochemical tests for proliferating cell nuclear antigen and caspase-3, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed at 6h, 24h, 48h, and 72h time intervals after PDT. The number of positive cells showing caspase-3 expression was significantly higher, mainly at 6h after PDT. In the first cycle of PDT, the highest frequency of positive cells for TUNEL was found at 24h. At 72h after PDT, proliferating cell nuclear antigen positive cells increased significantly, indicating that there was an epithelial response in direction towards DNA repair and cell proliferation at this time. Because cell proliferation increases and cell death index decreases at 72h after PDT, it is recommended that the interval between the PDT sessions must not be longer than 2days up to total lesion remission. PMID:23892188

Barcessat, Ana Rita; Huang, Isaac; Rosin, Flávia Perillo; dos Santos Pinto, Décio; Maria Zezell, Denise; Corręa, Luciana

2013-09-01

22

Salivary copper and zinc levels in oral pre-malignant and malignant lesions  

PubMed Central

Recent technological advances have made saliva as a tool for diagnosis of many things; among them are hormone imbalances, liver function, immunodeficiency and even cancer. Aim: The present study was done to evaluate the levels of copper and zinc and copper/zinc ratio in saliva of premalignant and malignant lesions of oral cavity, because of the anatomical proximity of the saliva to both premalignant and malignant oral neoplasms. Materials and Methods: The levels of copper and zinc were estimated in the saliva of 5 patients with oral submucous fibrosis, 5 patients with oral leukoplakia, 5 patients with oral lichen planus and 10 patients with oral squamous cell carcinoma of oral cavity using inductively coupled mass spectrometry (ICP- MS). The values were compared with 6 normal age and sex matched control subjects. Results: There was significant difference of the mean salivary copper and zinc levels of premalignant and malignant lesions when compared to the normal controls. In oral cancer patients there was significant difference in the copper levels according the histodifferentiaton in squamous cell carcinoma. Within the premalignant group the copper levels were more in the oral sub mucous fibrosis when compared to the leukoplakia and lichen planus. Copper zinc ratio decreased in premalignant and malignant group when compared to the normal group. Conclusions: Saliva may be used as a potential diagnostic tool, which can be efficiently employed to evaluate the copper and zinc levels in pre malignant and malignant lesions of oral cavity. Key words: Copper, inductively couples mass spectrometry, leukoplakia, lichen planus, oral squamous cell carcinoma, oral submucous fibrosis, saliva, zinc

Ayinampudi, Bhargavi Krishna; Narsimhan, Malathi

2012-01-01

23

Oral non-squamous malignant tumors; diagnosis and treatment  

Microsoft Academic Search

Some 90% of oral cancers consist of squamous cell carcinomas that arise from the oral mucosa. The remaining 10% of malignancies consist of malignant melanomas, carcinomas of the intraoral salivary glands, sarcomas of the soft tis- sues and the bones, malignant odontogenic tumors, non-Hodgkin's lymphomas and metastases from primary tumors located elsewhere in the body. These malignancies will be briefly

Rutger van der Waal; Isaäc van der Waal

24

Malignant melanoma of the oral cavity: Report of two cases  

PubMed Central

Primary malignant melanoma is a rare and aggressive neoplasm that originates from the proliferation of melanocytes. Although, it comprises 1.3% of all cancers, malignant melanoma of the oral cavity accounts for only 0.2-8% of all reported melanomas and occurs approximately 4 times more frequently in the oral mucosa of the upper jaw, usually on the palate or alveolar gingivae. Most of the mucosal melanomas are usually asymptomatic in early stages, and presents as pigmented patch or a mass delaying the diagnosis until symptoms of swelling, ulceration, bleeding, or loosening of teeth are noted. The prognosis is extremely poor, especially in advanced stages. Therefore, any pigmented lesion of undetermined origin should always be biopsied. We herewith report of two cases of oral malignant melanoma in a 60 and 75-year-old female.

Munde, Anita; Juvekar, Monica Vivek; Karle, Ravindra R.; Wankhede, Pranali

2014-01-01

25

Malignant melanoma of the oral cavity: Report of two cases.  

PubMed

Primary malignant melanoma is a rare and aggressive neoplasm that originates from the proliferation of melanocytes. Although, it comprises 1.3% of all cancers, malignant melanoma of the oral cavity accounts for only 0.2-8% of all reported melanomas and occurs approximately 4 times more frequently in the oral mucosa of the upper jaw, usually on the palate or alveolar gingivae. Most of the mucosal melanomas are usually asymptomatic in early stages, and presents as pigmented patch or a mass delaying the diagnosis until symptoms of swelling, ulceration, bleeding, or loosening of teeth are noted. The prognosis is extremely poor, especially in advanced stages. Therefore, any pigmented lesion of undetermined origin should always be biopsied. We herewith report of two cases of oral malignant melanoma in a 60 and 75-year-old female. PMID:24963252

Munde, Anita; Juvekar, Monica Vivek; Karle, Ravindra R; Wankhede, Pranali

2014-04-01

26

Detection of galectins during malignant transformation of oral cells  

PubMed Central

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

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

2013-01-01

27

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

PubMed

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

Angadi, Punnya V; Krishnapillai, Rekha

2012-09-01

28

Malignant Epithelioid Schwannoma of the Oral Cavity in a Cat  

PubMed Central

ABSTRACT A malignant epithelioid schwannoma of the oral cavity was diagnosed in an 8-year-old domestic short-hair cat. The mass was located in the gingiva of the upper left premolar to molar region and showed multinodular growth patterns. The mass comprised epithelioid cells arranged in densely packed sheets. Tumor cells had large, round to oval nuclei with prominent nucleoli and an abundant eosinophilic cytoplasm. Immunohistochemically, most of the tumor cells were positive for S-100 protein, glial fibrillary acidic protein and vimentin, but all lacked melanoma-associated antigen and muscle and neuroendocrine markers. Stains for type IV collagen showed linear immunoreactivity around single cells and groups of cells. Ultrastructurally, tumor cells were separated by a well-defined basement membrane, and interdigitating cell processes were observed. To our knowledge, this is the first report of feline malignant epithelioid schwannoma.

BOONSRIROJ, Hassadin; KIMITSUKI, Kazunori; AKAGI, Tetsuya; PARK, Chun-Ho

2014-01-01

29

Optical detection of (pre-)malignant lesions of the oral mucosa: autofluorescence characteristics of healthy mucosa  

NASA Astrophysics Data System (ADS)

Previous clinical results demonstrate the potential of in vivo autofluorescence spectroscopy for early detection of (pre-)malignant lesions of the oral mucosa. For reliable diagnosis, it is necessary to study autofluorescence spectra of healthy mucosa first. We measured excitation-emission maps in healthy subjects and subjects with a history of cancer in the head -neck region. Our results show that different anatomical locations produce distinct autofluorescence spectra. Influences of, among others, smoking and drinking habits require further investigation.

de Veld, Diana C. G.; Witjes, Max; Roodenburg, Jan L.; Star, Willem M.; Sterenborg, Hericus J. C. M.

2001-10-01

30

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

PubMed Central

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

2013-01-01

31

Survivin, a Potential Early Predictor of Tumor Progression in the Oral Mucosa  

Microsoft Academic Search

Survivin is a recently described apoptosis inhibitor selectively over-expressed in most tumors. Immunohistochemistry was used to investigate a potential role of survivin as an early predictor of malignant transformation in precancerous and cancerous lesions of the oral cavity. Survivin was present in 10\\/30 cases (33%) of oral precancerous lesions without malignant progression, and in 15\\/16 cases (94%) of oral precancerous

L. Lo Muzio; G. Pannone; R. Leonardi; S. Staibano; M. D. Mignogna; G. De Rosa; Y. Kudo; T. Takata; D. C. Altieri

2003-01-01

32

Assessment of p53 protein expression in normal, benign, and malignant oral mucosa.  

PubMed

Recent studies have shown the accumulation of high levels of p53 protein to be associated with malignant disease, within a range of tissues. This paper assesses p53 expression in oral mucosal disease. Biopsies were obtained from a range of oral disorders which included normal, benign, premalignant, and malignant oral tissue. In addition, oral smears were obtained from a limited number of patients with biopsy-proven oral cancer. Expression of the p53 protein was assessed using the polyclonal antibody CM1, together with a standard immunoperoxidase technique. A total of 37 oral cancers were assessed, of which 20 were found to express the p53 protein (54 per cent of cases). The p53 protein was not identified in normal, benign, or premalignant oral mucosa (54 cases). The identification of p53 within biopsies of oral mucosal lesions would appear to correlate with oral malignancy. PMID:1381431

Ogden, G R; Kiddie, R A; Lunny, D P; Lane, D P

1992-04-01

33

A retrospective clinicopathological study on oral lichen planus and malignant transformation: Analysis of 518 cases  

PubMed Central

Objective: To investigate the epidemiological and clinical characteristics of a relatively large cohort of patients with oral lichen planus (OLP) from eastern China. Study design: A total of 518 patients with histologically confirmed OLP in a long-term follow-up period (6 months-21.5 years) were retrospectively reviewed in our clinic. Results: Of the 518 patients, 353 females and 165 males were identified. The average age at diagnosis was 46.3 years (range 9-81 years) with the buccal mucosa being the most common site (87.8%). At initial presentation, white lichen and red lichen was seen in 52.3% and 47.7% patients, respectively. Of these, 5 (0.96%) patients previously diagnosed clinically and histopathologically as OLP developed oral cancer. All of them were the females with no a history of smoking or alcohol use. Conclusions: Clinical features of eastern Chinese OLP patients were elucidated. Notably, approximately 1% of OLP developed into cancer, which provides further evidence of potentially malignant nature of OLP. Key words:Oral lichen planus, clinical features, malignant transformation, oral cancer.

Shen, Zheng Y.; Zhu, Lai K.; Feng, Jin Q.; Tang, Guo Y.; Zhou, Zeng T.

2012-01-01

34

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

PubMed Central

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.

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

2014-01-01

35

Risk factors for leukoplakia and malignant transformation to oral carcinoma: a leukoplakia cohort in Taiwan  

Microsoft Academic Search

The effects of betel nut chewing, smoking and alcohol on the occurrence of leukoplakia and its malignant transformation to oral carcinoma were quantified in a leukoplakia cohort (n = 435) from one medical centre between 1988 and 1998 in Taiwan. Sixty oral carcinomas were ascertained in this cohort. A case–control study within the leukoplakia cohort was used to study, risk

M N Shiu; T H H Chen; S H Chang; L J Hahn

2000-01-01

36

Potential Oral Health Benefits of Cranberry  

Microsoft Academic Search

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

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

2008-01-01

37

Mast Cells and Angiogenesis in Oral Malignant and Premalignant Lesions  

PubMed Central

Mast cell contribution to neoangiogenesis during tumorigenesis in oral squamous cell carcinoma is not determined yet. Objectives: To associate numerical mast cell density (MCD) to numerical microvessel density (MVD) during the progression of oral leukoplakia without dysplasia and leukoplakia with dysplasia to squamous cell carcinoma (OSCC). Materials and methods: MVD was analysed immunohistochemically (mouse monoclonal anti-human CD34) in 49 paraffin-embedded specimens, 35 OSCCs, 9 leukoplakias and 5 normal oral tissues. Toluidine blue counterstaining revealed mast cells. MCD and MVD were assessed at the same optical field. Results: MVD increased between: normal oral mucosa, dysplasia (p=0.004), OSCC (p=0.001), leukoplakia and OSCC (p=0.041). MCD increased between: normal oral mucosa, dysplasia (p=0.003), OSCC (p=0.000), leukoplakia and OSCC (p=0.007). MVD was found to depend on MCD (p=0.000) in a percent 28.3% (power curve fit model). Conclusions: Mast cells are attracted at the lesion site and may turn on an angiogenic switch during tumorigenesis in OSCC.

Michailidou, E.Z; Markopoulos, A.K; Antoniades, D.Z

2008-01-01

38

Malignant lymphoma associated with rheumatoid arthritis, developing shortly after initiation of oral methotrexate.  

PubMed

We report a patient with rheumatoid arthritis (RA) who developed malignant lymphoma of the diffuse large B-cell type in the right submandibular region shortly after initiation of oral methotrexate (MTX). Despite cessation of MTX, the lymphadenopathy did not regress, and only reached complete remission after 3 courses of CHOP therapy followed by irradiation. In this patient highly active RA itself was considered to be the main cause of malignant lymphoma, and MTX might have contributed to the development by modifying the immune system. When RA is highly active, MTX should be used carefully because of the possible development of malignant lymphoma as well as other serious complications. PMID:15005257

Gono, Takahisa; Shimojima, Yasuhiro; Hoshi, Kenichi; Yamamoto, Kanji; Tokuda, Takahiko; Shikama, Naoto; Matsuda, Masayuki; Ikeda, Shu-ichi

2004-02-01

39

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

PubMed Central

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.

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

2006-01-01

40

Proliferating cell nuclear antigen in malignant and pre-malignant lesions of epithelial origin in the oral cavity and the skin: an immunohistochemical study  

Microsoft Academic Search

Summary Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the late G1 and S phase of the cell cycle and immunohistochemical detection of the protein represents a useful marker for the proliferating fraction of cells in tissue specimens. A series of malignant and pre-malignant lesions of the oral cavity and skin were evaluated by the streptavidin biotin

T. Tsuji; P. Shrestha; K. Yamada; H. Takagi; F. Shinozaki; K. Sasaki; K. Maeda; M. Mori

1992-01-01

41

The thrombotic potential of oral pathogens  

PubMed Central

In recent times the concept of infectious agents playing a role in cardiovascular disease has attracted much attention. Chronic oral disease such as periodontitis, provides a plausible route for entry of bacteria to the circulation. Upon entry to the circulation, the oral bacteria interact with platelets. It has been proposed that their ability to induce platelet aggregation and support platelet adhesion is a critical step in the pathogenesis of the infection process. Many published studies have demonstrated multiple mechanisms through which oral bacteria are able to bind to and activate platelets. This paper will review the various mechanisms oral bacteria use to interact with platelets.

Kerrigan, Steven W.; Cox, Dermot

2009-01-01

42

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

NASA Astrophysics Data System (ADS)

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

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

2008-11-01

43

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

SciTech Connect

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

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

2005-12-15

44

Expression of melanocytic differentiation markers in malignant melanomas of the oral and sinonasal mucosa.  

PubMed

Malignant melanomas of the oral and sinonasal mucosa are rare tumors. Amelanotic variants can, on occasion, be difficult to recognize by routine light microscopy. Immunohistochemical studies may be needed for a final diagnosis. A number of new monoclonal antibodies to melanocytic differentiation antigens have been studied recently on primary cutaneous and metastatic melanoma. However, little is known about these antibodies for the diagnosis of mucosal melanomas. In this study the authors analyzed 79 oral and sinonasal mucosal melanomas of 65 patients. A total of 35 tumors originated from the oral mucosa (21 primary tumors, eight local recurrences, and six metastases) and 44 melanomas were from the sinonasal tract (27 primary tumors, nine local recurrences, and eight metastases). Immunohistochemical studies were performed on paraffin-embedded tissues, using the following antibodies: anti-S-100 protein, T311 (anti-tyrosinase), A103 (anti-Mart-1/Melan-A), D5 (antimicrophthalmia-associated transcription factor), and HMB-45 (anti-gp100). Of 35 oral mucosal tumors, 34 (97%) were positive with anti-S-100 protein, 33 (94%) with T311, 30 (85%) with A103, 26 (74%) with D5, and 25 (71%) with HMB-45. All five desmoplastic melanomas of the oral mucosa were positive for S-100 protein, four for tyrosinase, and one each for HMB-45 and A103. No desmoplastic melanoma was positive with D5. All 44 sinonasal melanomas were positive for tyrosinase and Mart-1/Melan-A (100%). Forty-three (98%) were positive with HMB-45, 42 (95%) with anti-S-100 protein, and 40 (91%) with D5. These results reveal that T311 is the most sensitive marker for sinonasal melanomas and closely approaches the sensitivity of anti-S-100 protein for oral mucosal melanomas. For desmoplastic mucosal tumors, anti-S-100 protein remains the most sensitive marker. PMID:11395556

Prasad, M L; Jungbluth, A A; Iversen, K; Huvos, A G; Busam, K J

2001-06-01

45

Pharmacokinetics of different formulations of oral azacitidine (CC-486) and the effect of food and modified gastric pH on pharmacokinetics in subjects with hematologic malignancies.  

PubMed

Parenteral azacitidine improves overall survival in higher-risk myelodysplastic syndromes. An oral azacitidine formulation would allow extended dosing schedules, potentially improving safety and/or efficacy. Two Phase 1 studies evaluated the pharmacokinetics (PK) of oral azacitidine in subjects with hematologic malignancies. Study 1 evaluated different oral formulations (immediate release tablet [IRT], enteric-coated tablet, and capsule; N?=?16). Study 2 assessed the effect of food (Part 1; N?=?17) and gastric pH modulation with omeprazole (Part 2; N?=?14) on oral azacitidine PK. Azacitidine plasma concentration-time profiles for IRT and capsule formulations were similar, with more rapid time to maximum plasma concentration (Tmax ) than the enteric-coated tablet. Study 2 evaluated only IRT formulations of oral azacitidine. Under fed condition, Tmax was delayed ?1.5?hours but area under the concentration-time curve (AUC? ) and maximum plasma concentrations (Cmax ) were comparable under fed and fasted conditions. Mean azacitidine AUC? and Cmax increased upon omeprazole co-administration (18.3% and 13.2%, respectively, vs. oral azacitidine alone), but not to a clinically meaningful extent. High inter-subject variability in AUC? and Cmax (%CV range 46.4-68.9%) was observed. Oral azacitidine is rapidly absorbed with little or no effect of food on PK parameters, and does not require dose adjustments when taking a proton-pump inhibitor. PMID:24374798

Laille, Eric; Savona, Michael R; Scott, Bart L; Boyd, Thomas E; Dong, Qian; Skikne, Barry

2014-06-01

46

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

PubMed Central

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.

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

2009-01-01

47

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

PubMed Central

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

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

48

Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: A dose escalation and pharmacologic study1  

PubMed Central

We determined the maximum tolerated dose (MTD), toxicity profile, pharmacokinetic parameters, and preliminary efficacy data of oral sodium phenylbutyrate (PB) in patients with recurrent malignant gliomas. Twenty-three patients with supratentorial recurrent malignant gliomas were enrolled on this dose escalation trial. Four dose levels of PB were studied: 9, 18, 27, and 36 g/day. Data were collected to assess toxicity, response, survival, and pharmacokinetics. All PB doses of 9, 18, and 27 g/day were well tolerated. At 36 g/day, two of four patients developed dose-limiting grade 3 fatigue and somnolence. At the MTD of 27 g/day, one of seven patients developed reversible grade 3 somnolence. Median survival from time of study entry was 5.4 months. One patient had a complete response for five years, and no partial responses were noted, which yielded an overall response rate of 5%. Plasma concentrations of 706, 818, 1225, and 1605 ?M were achieved with doses of 9, 18, 27, and 36 g/day, respectively. The mean value for PB clearance in this patient population was 22 liters/h, which is significantly higher than the 16 liters/h reported in patients with other malignancies who were not receiving P450 enzyme–inducing anticonvulsant drugs (P = 0.038). This study defines the MTD and recommended phase 2 dose of PB at 27 g/day for heavily pretreated patients with recurrent gliomas. The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants.

Phuphanich, Surasak; Baker, Sharyn D.; Grossman, Stuart A.; Carson, Kathryn A.; Gilbert, Mark R.; Fisher, Joy D.; Carducci, Michael A.

2005-01-01

49

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

PubMed Central

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

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

2013-01-01

50

Salivary protein markers: a noninvasive protein profile-based method for the early diagnosis of oral premalignancy and malignancy.  

PubMed

An ultra-sensitive hyphenated technique, high-performance liquid chromatography-laser-induced fluorescence detection protein profiling of saliva, is evaluated for early detection and diagnosis of oral premalignancy and malignancy. Calibration sets of protein profiles of unstimulated whole saliva are collected from clinically/pathologically normal, premalignant, and malignant subjects and used as standards. Three parameters-scores of factors, sum of squared residuals, and Mahalanobis distance-derived from principal component analysis of protein profiles of the standard calibration sets, and blind samples are used for "match/no-match" diagnosis of the blind samples. Analyses of the results show that the method is capable of differentiating normal, premalignant, and malignant conditions with the sensitivity and specificity of 79% and 78%, respectively. The technique provides a fast, highly objective (free from personal judgment and statistically defined), and noninvasive diagnostic method for screening and early detection of oral cancer. PMID:23958948

Patil, Ajeetkumar; Choudhari, Khoobram S; Unnikrishnan, Vayakkara Kolaprath; Shenoy, Nandita; Ongole, Ravikiran; Pai, Keerthilatha M; Kartha, Vasudevan Bhaskaran; Chidangil, Santhosh

2013-10-01

51

SLURP-1 and -2 in normal, immortalized and malignant oral keratinocytes  

PubMed Central

The secreted mammalian Ly-6/urokinase plasminogen activator receptor-related proteins (SLURP)-1 and -2 are produced by keratinocytes comprising the mucocutaneous epithelium. They regulate in autocrine and paracrine ways cell growth and differentiation through the nicotinic acetylcholine receptors (nAChRs) expressed on the plasma membrane. Keratinocyte nAChRs are targeted by tobacco-derived carcinogenic nitrosamines 4-(methylnitrosamino)-1-(3–pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) that can induce tumorigenic transformation of Het-1A keratinocytes. In this study we asked if SLURPs could abolish tumorigenic effects of nitrosamines. Preincubation with either recombinant SLURP-1 or -2 in both cases considerably reduced the number of colonies in soft agar, and the number of tumor nodules >0.5 cm in diameter in Nu/Nu mice produced by Het-1A cells treated with nitrosamines. The levels of SLURP-1 and -2 mRNA transcripts in nitrosamine-transformed Het-1A cells as well as in the tumor cell lines SCC-25 and FaDu were significantly (p<0.05) less compared to normal gingival keratinocytes, which are probably the major source of the secreted SLURPs found in a sample of human saliva. The expression of SLURPs was decreased due to gene silencing of different nAChR ? subunits with small hairpin RNA, suggesting that a positive feedback regulation is altered in malignant cells. Thus, SLURP-1 and -2 are efficient autocrine and paracrine ligands of keratinocyte nAChRs capable of preventing tobacco nitrosamine-induced malignant transformation of oral cells. These “proof-of-concept” preliminary results have salient clinical implications.

Arredondo, Juan; Chernyavsky, Alexander I.; Grando, Sergei A.

2007-01-01

52

Current Aspects on Oral Squamous Cell Carcinoma  

PubMed Central

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.

Markopoulos, Anastasios K

2012-01-01

53

Voriconazole and its clinical potential in the prophylaxis of systemic fungal infection in patients with hematologic malignancies: a perspective review  

PubMed Central

Invasive fungal infections (IFIs) have become high prevalence in patients with hematologic malignancies. Drug-based strategies for IFIs include various approaches such as prophylactic, empiric, preemptive, and directed treatment. Prophylaxis is an attractive strategy in high-risk patients, given the lack of reliable diagnostics and the high mortality rate associated with IFIs. Prophylaxis includes the use of antifungal drugs in all patients at risk. An ideal antifungal compound for prophylaxis should have a potent and broad activity, be available both orally and intravenously, and have a low toxicity profile. Voriconazole fulfills all these criteria. The clinical efficacy of voriconazole against the majority of fungal pathogens makes it potentially very useful for the prevention of IFIs in patients with hematologic malignancies. Voriconazole appears to be very effective for the primary and secondary prevention of IFIs in these patients and recipients of allogeneic hematopoietic stem-cell transplantation. Randomized controlled trials evaluating voriconazole as primary antifungal prophylaxis in patients with neutropenia treated for a variety of hematologic malignancies have been performed, confirming its value as a prophylactic agent. Voriconazole is generally safe and well tolerated; however, its use is also associated with a number of concerns. In most patients with hematologic malignancies there is the potential for pharmacokinetic drug–drug interactions given that voriconazole is metabolized through the P450 cytochrome system.

Zabalza, Amaya; Gorosquieta, Ana; Equiza, Encarnacion Perez

2013-01-01

54

Borderline breast core needle histology: predictive values for malignancy in lesions of uncertain malignant potential (B3)  

PubMed Central

Breast core needle biopsy (CNB) is an accurate test but may result in borderline histology (lesions of uncertain malignant potential or B3). This is an evaluation of the largest series (to date) of B3 histology, which focusses on estimating positive predictive values (PPV) for malignancy. We identified all B3 CNBs over a 10-year period in a single institution (N=372) from a series of 4035 consecutive needle biopsies. We describe the imaging findings, and report excision histology outcomes (N=279) and category-specific PPV for B3 lesions using two approaches including estimates based on subjects who had either excision or follow-up (N=328). B3 represented 9.2% of all CNB results. Excision histology was benign in 181 (64.9%) and malignant in 98 (35.1%) subjects (61 ductal carcinoma in situ, 37 invasive carcinoma). Positive predictive value for malignancy (based on excision histology) was 35.1% (95% CI: 29.5–40.7) and PPV (based on excision or review) was 29.9% (95% CI: 24.9–34.8). Lesion-specific PPV (estimates in parentheses for excision or follow-up) was atypical ductal hyperplasia 44.7% (40.6%); lobular intraepithelial neoplasia 60.9% (58.3%); papillary lesion 22.7% (15.9%); radial scar 16.7% (12.3%); phyllodes tumour 12.5% (12.5%); and B3 not specified 20.0%. Approximately one-third of CNB results classified as B3 are malignant on excision, and the likelihood of malignancy varies substantially between specific lesion groups. Whereas cases may be selectively managed without surgery, the majority warrant excision biopsy based on our estimates. Research is needed to improve differentiation between malignant and benign diseases in B3 lesions using diagnostic or predictive methods.

Houssami, N; Ciatto, S; Bilous, M; Vezzosi, V; Bianchi, S

2007-01-01

55

Borderline breast core needle histology: predictive values for malignancy in lesions of uncertain malignant potential (B3).  

PubMed

Breast core needle biopsy (CNB) is an accurate test but may result in borderline histology (lesions of uncertain malignant potential or B3). This is an evaluation of the largest series (to date) of B3 histology, which focuses on estimating positive predictive values (PPV) for malignancy. We identified all B3 CNBs over a 10-year period in a single institution (N=372) from a series of 4035 consecutive needle biopsies. We describe the imaging findings, and report excision histology outcomes (N=279) and category-specific PPV for B3 lesions using two approaches including estimates based on subjects who had either excision or follow-up (N=328). B3 represented 9.2% of all CNB results. Excision histology was benign in 181 (64.9%) and malignant in 98 (35.1%) subjects (61 ductal carcinoma in situ, 37 invasive carcinoma). Positive predictive value for malignancy (based on excision histology) was 35.1% (95% CI: 29.5-40.7) and PPV (based on excision or review) was 29.9% (95% CI: 24.9-34.8). Lesion-specific PPV (estimates in parentheses for excision or follow-up) was atypical ductal hyperplasia 44.7% (40.6%); lobular intraepithelial neoplasia 60.9% (58.3%); papillary lesion 22.7% (15.9%); radial scar 16.7% (12.3%); phyllodes tumour 12.5% (12.5%); and B3 not specified 20.0%. Approximately one-third of CNB results classified as B3 are malignant on excision, and the likelihood of malignancy varies substantially between specific lesion groups. Whereas cases may be selectively managed without surgery, the majority warrant excision biopsy based on our estimates. Research is needed to improve differentiation between malignant and benign diseases in B3 lesions using diagnostic or predictive methods. PMID:17438578

Houssami, N; Ciatto, S; Bilous, M; Vezzosi, V; Bianchi, S

2007-04-23

56

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

PubMed Central

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.

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

1981-01-01

57

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

PubMed Central

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.

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

2013-01-01

58

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 Central

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.

NAGAO, YUMIKO; SATA, MICHIO

2013-01-01

59

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

PubMed Central

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

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

2012-01-01

60

A Case of Laparoscopic Radical Prostatectomy for a Prostatic Stromal Tumor of Uncertain Malignant Potential  

PubMed Central

Prostatic stromal tumor of uncertain malignant potential (STUMP) is a rare neoplasm with distinctive clinical and pathological characteristics. Here we report a case of laparoscopic radical prostatectomy performed in a patient with prostatic STUMP.

Kwak, Kyung Won; Jo, Dae Jin; Lee, Eun Hee; Ryu, Dong Soo

2011-01-01

61

Lactobacillus casei potentiates induction of oral tolerance in experimental arthritis.  

PubMed

Probiotics have been shown to exert beneficial effects on modulation of diverse diseases. However, no information is available for the effect of probiotics in the induction of oral tolerance in autoimmune diseases. The main purpose of this study was to elucidate whether Lactobacillus casei (L. casei) affect the induction of oral tolerance in experimental rheumatoid arthritis (RA). Type II collagen (CII) alone or together with L. casei was orally administered into collagen-induced arthritis (CIA) rats, and its effects on the clinical and histopathological aspects of RA were investigated. Co-administration of L. casei with CII more effectively suppressed clinical symptoms, paw swelling, lymphocyte infiltration and destruction of cartilage tissues of experimental arthritis than the rats treated with CII alone. The enhanced therapeutic efficacy was associated with an increase in anti-inflammatory cytokines (IL-10 and TGF-beta) while decreasing pro-inflammatory cytokines (IL-1beta, IL-2, IL-6, IL-12, IL-17, IFN-gamma and TNF-alpha). Co-administration of L. casei with CII more effectively suppressed CII-reactive T cell proliferation and the levels of Th1-type IgG isotypes (IgG2a and IgG2b), while up-regulating Foxp3 expression levels and the population of Foxp3(+) CD4(+) T cells. Our study provides evidence that L. casei could potentiate antigen-specific oral tolerance and suppress Th1-type immune responses of arthritic inflammation. PMID:18804867

So, Jae-Seon; Lee, Choong-Gu; Kwon, Ho-Keun; Yi, Hwa-Jung; Chae, Chang-Suk; Park, Jin-A; Hwang, Ki-Chul; Im, Sin-Hyeog

2008-11-01

62

A potential individual cell malignancy indicator: focal length  

NASA Astrophysics Data System (ADS)

The label-free technique of optofluidic intracavity spectroscopy (OFIS) utilizes the optical transmission spectrum of a cell in a microfluidic Fabry-Pérot (F-P) cavity to distinguish cells from cancerous cell lines and baseline normal blood cells. The classification between canine hemangiosarcoma (HSA) cancer cells and monocytes in canine normal peripheral blood mononuclear cells (PBMCs) had been demonstrated with 95% sensitivity and 98% specificity. Now with a new optical model that treats the cell settled at the bottom of the cavity as a thin lens, the focal length of cells was extracted and used as an individual cell malignancy indicator.

Wang, Weina; Lear, Kevin L.

2011-02-01

63

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

PubMed Central

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

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

2013-01-01

64

Organotypic culture of normal, dysplastic and squamous cell carcinoma-derived oral cell lines reveals loss of spatial regulation of CD44 and p75 NTR in malignancy.  

PubMed

Oral squamous cell carcinomas (OSCC) often arise from dysplastic lesions. The role of cancer stem cells in tumour initiation is widely accepted, yet the potential existence of pre-cancerous stem cells in dysplastic tissue has received little attention. Cell lines from oral diseases ranging in severity from dysplasia to malignancy provide opportunity to investigate the involvement of stem cells in malignant progression from dysplasia. Stem cells are functionally defined by their ability to generate hierarchical tissue structures in consortium with spatial regulation. Organotypic cultures readily display tissue hierarchy in vitro; hence, in this study, we compared hierarchical expression of stem cell-associated markers in dermis-based organotypic cultures of oral epithelial cells from normal tissue (OKF6-TERT2), mild dysplasia (DOK), severe dysplasia (POE-9n) and OSCC (PE/CA P J15). Expression of CD44, p75(NTR), CD24 and ALDH was studied in monolayers by flow cytometry and in organotypic cultures by immunohistochemistry. Spatial regulation of CD44 and p75(NTR) was evident for organotypic cultures of normal (OKF6-TERT2) and dysplasia (DOK and POE-9n) but was lacking for OSCC (PE/CA PJ15)-derived cells. Spatial regulation of CD24 was not evident. All monolayer cultures exhibited CD44, p75(NTR), CD24 antigens and ALDH activity (ALDEFLUOR(®) assay), with a trend towards loss of population heterogeneity that mirrored disease severity. In monolayer, increased FOXA1 and decreased FOXA2 expression correlated with disease severity, but OCT3/4, Sox2 and NANOG did not. We conclude that dermis-based organotypic cultures give opportunity to investigate the mechanisms that underlie loss of spatial regulation of stem cell markers seen with OSCC-derived cells. PMID:22643025

Dalley, Andrew J; AbdulMajeed, Ahmad A; Upton, Zee; Farah, Camile S

2013-01-01

65

[Prostatic stromal tumors of uncertain malignant potential (STUMP): A case report].  

PubMed

We report the case of a patient affected by a voluminous prostatic tumor for which the histological analysis conclude in a stromal tumor of uncertain malignant potential. This type of tumor is rare, but requires to be individualized to differentiate it from a benign prostatic hyperplasia or a sarcoma of the prostate. The therapeutic care must be made keeping in mind the risk of degeneration towards a malignant shape. PMID:24950874

Michaud, Sébastien; Moreau, Anne; Braud, Guillaume; Renaudin, Karine; Branchereau, Julien; Bouchot, Olivier; Rigaud, Jérôme

2014-06-01

66

MRI findings of prostate stromal tumour of uncertain malignant potential: a case report  

PubMed Central

Prostatic stromal tumours are rare neoplasias that include benign, malignant and borderline lesions. Stromal tumour of uncertain malignant potential (STUMP) has been recently described and only a few reports exist in the literature. As a rare and distinct neoplasia, to date, there is no description of MRI findings of prostate STUMP. In this article, we describe the clinical and MRI features with histopathological correlation of a patient with prostate STUMP.

Muglia, V F; Saber, G; Maggioni, G; Monteiro, A J C

2011-01-01

67

Evaluating oral noncombustible potential-reduced exposure products for smokers  

PubMed Central

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.

Eissenberg, Thomas

2010-01-01

68

Invasive fungal infections in pediatric patients with hematologic malignancies receiving oral amphotericin B solution and early intravenous administration of fluconazole.  

PubMed

This study aimed to determine the frequency of invasive fungal infection (IFI) in pediatric patients with hematologic malignancy who received amphotericin B oral suspension and early intravenous fluconazole during the neutropenic phase as prophylaxis for IFI. Records of 743 neutropenic episodes induced by cytotoxic chemotherapy between 1997 and 2008 were retrospectively reviewed to determine risk factors for and frequency of IFI. The overall frequency of IFI was 0.8% (n=6) and frequencies of proven, probable, and possible infections were 0.3% (n=2), 0.4% (n=3), and 0.1% (n=1), respectively. During 351 episodes of profound neutropenia (neutrophil count <500/?L for ? 14 d), overall incidence of IFI was 1.71% (n=6). Pulmonary aspergillosis was the most common causative agent, and no patients showed candidemia, or hepatosplenic candidiasis. Cytotoxic chemotherapy regimens for acute myelogenous leukemia and profound neutropenia were significantly associated with IFI (P=0.004 and P=0.009, respectively). No IFI-attributable deaths or breakthrough fungal infections occurred. Our results indicate that amphotericin B oral solution and early intravenous fluconazole may be effective in reducing the incidence and mortality of IFI in pediatric patients with hematologic malignancies. PMID:21464763

Watanabe, Nobuhiro; Matsumoto, Kimikazu; Kojima, Seiji; Kato, Koji

2011-05-01

69

Serum metalloproteinases and their inhibitors: markers for malignant potential.  

PubMed Central

Death from cancer results from the development of metastases or local progression of tumour. Metastasis and local progression may result from the inappropriate activity of metalloproteinases released by tumour cells or of their regulatory peptides. We have developed quantitative assays for interstitial collagenase, stromelysin 1 and tissue inhibitors of metalloproteinase (TIMP) 1 and 2, which have allowed the study of serum levels of these proteins. Sera from 40 patients with prostatic cancer, stored prior to and after 6 and 12 months' treatment with a gonadotrophin-releasing hormone agonist and an anti-androgen were analysed. Levels were compared with two control groups, comprising 21 patients with active rheumatoid arthritis and 56 age-matched hospital attenders without arthritis or cancer. Contrasting levels have been found in patients with prostatic cancer as compared with hospital controls without cancer and patients with rheumatoid arthritis. Patients with prostatic cancer had higher levels of TIMP-1 and collagenase (P = 0.0001) and lower levels of TIMP-2 (P = 0.003) than controls. Patients with metastatic cancer had significantly higher levels of collagenase than those without metastases (P = 0.02). Patients with rheumatoid arthritis had significantly higher levels of stromelysin than either controls (P = 0.002) or patients with cancer (P = 0.008). Serum tissue inhibitor of metalloproteinase 1 in combination with collagenase levels was as sensitive as prostate-specific antigen as a marker of metastatic disease. These findings provide a basis for the investigation of the role of metalloproteinases and their inhibitors in other malignancies.

Baker, T.; Tickle, S.; Wasan, H.; Docherty, A.; Isenberg, D.; Waxman, J.

1994-01-01

70

Primary care clinicians and the detection and referral of potentially malignant disorders in the mouth: a summary of the current evidence.  

PubMed

The importance of detecting oral malignant disease is paramount. Recent government strategies have placed an emphasis on the early detection of cancer. This paper presents a brief account of the current debate around the role of oral cancer screening and provides a summary of the results of three practice-based studies that were supported by the British Society for General Dental Surgery and the Faculty of General Dental Practice (UK). Overall, there appears to be a lack of rigour among some general dental practitioners when screening for potentially malignant disorders and their incidence in dental practice is perceived to be low. Barriers remain to the implementation of smoking-cessation schemes and many general dental practitioners feel out of their depth in tackling the abuse of alcohol, despite recognising its importance as a risk factor. Patients continue to present to their general medical practitioner (GMP) when they are concerned about something in their mouth that is not related to their teeth. GMPs' ability to manage early oral cancer is discussed. A prospective randomised controlled trial (RCT), or a demonstration study, is recommended to investigate the numbers of cases of oral cancer diagnosed in primary dental care and primary medical care and to develop standardised referral criteria for early cases of this disease to reduce under- and over-referral. The RCT could also examine the potential of using auxiliary healthcare workers and examine the impact of such a programme upon secondary care services. PMID:20353654

Brocklehurst, Paul R; Baker, Sarah R; Speight, Paul M

2010-04-01

71

Chemoprevention of premalignant and malignant lesions of oral cavity: Recent trends  

PubMed Central

The word chemoprevention includes prevention of initiation, promotion, and progression of carcinogenesis to cancer. This article is an attempt to review the dietary chemopreventive agents and their mode of action in chemoprevention of oral premalignant lesions and oral cancer using a systematic approach. Selected chemoprevention trials are discussed with a focus on strategies of trial design and clinical outcome. Future in the field of chemoprevention will be more promising than the recently available therapeutic alternatives.

Bodhade, Ashish S.; Dive, Alka M.

2013-01-01

72

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

PubMed Central

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.

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

2014-01-01

73

A review of the recent literature regarding malignant transformation of oral lichen planus  

Microsoft Academic Search

On the basis of a literature review of the period 1950-1976, Krutchkoff et al questioned the possible premalignant nature of oral lichen planus. Their criticism was largely based on insufficiencies of data in support of the initial diagnoses of the condition. In this article, a review of the literature from the period 1977-1999 has been described; the criteria used were

Margot Van Dis; E. H. van der Meij; K. P. Schepman; L. E. Smeele; J. E. van der Wal; P. D. Bezemer; I. van der Waal

1999-01-01

74

Gene expression profiling of epithelial ovarian tumours correlated with malignant potential  

Microsoft Academic Search

BACKGROUND: Epithelial ovarian tumours exhibit a range of malignant potential, presenting distinct clinical phenotypes. Improved knowledge of gene expression changes and functional pathways associated with these clinical phenotypes may lead to new treatment targets, markers for early detection and a better understanding of disease progression. RESULTS: Gene expression profiling (Affymetrix, U95Av2) was carried out on 18 ovarian tumours including benign

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

2004-01-01

75

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

NASA Astrophysics Data System (ADS)

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

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

2006-03-01

76

Lactobacillus casei potentiates induction of oral tolerance in experimental arthritis  

Microsoft Academic Search

Probiotics have been shown to exert beneficial effects on modulation of diverse diseases. However, no information is available for the effect of probiotics in the induction of oral tolerance in autoimmune diseases. The main purpose of this study was to elucidate whether Lactobacillus casei (L. casei) affect the induction of oral tolerance in experimental rheumatoid arthritis (RA). Type II collagen

Jae-Seon So; Choong-Gu Lee; Ho-Keun Kwon; Hwa-Jung Yi; Chang-Suk Chae; Jin-A Park; Ki-Chul Hwang; Sin-Hyeog Im

2008-01-01

77

NOD1, RIP2 and Caspase12 are potentially novel biomarkers for oral squamous cell carcinoma development and progression  

PubMed Central

Although increasing studies have indicated that Nucleotide-oligomerization domain-containing protein 1 (NOD1) signaling could play an important role in gastrointestinal tumorigenesis, the protein expression and function of NOD1 signaling have not been understood well in oral squamous cell carcinoma (OSCC) progression. The objective of this study is, thus, to examine protein expression of NOD1 signaling immunohistochemically in normal, premalignant and malignant specimens of oral cavity, and to take insights into the association between the protein expression of NOD1 signaling pathway and OSCC precession. In this study immunohistochemical expression of NOD1, Receptor-interacting protein 2 (RIP2), Caspase12, human ? Defensin1, 2 and 3 (hBD1, 2, 3) was examined in 15 normal controls, 30 cases of oral leukoplakia (OLK) and 60 cases of OSCC. The immunostaining score was assessed by 2 pathologists, respectively. We found that the expression of NOD1, RIP2, Caspase12, hBD1, 2, and 3 decreased along with the progression of OSCC. NOD1 expression was correlated significantly to tumor differentiation, lymph node metastasis, and tumor size. Our results also showed the correlation of hBD2, 3 to lymph node metastasis of OSCC. These results suggest that the dysfunction of NOD1 signaling pathways could be associated with OSCC development and progression. NOD1, RIP2 and Caspase12 could be used as potentially novel biomarkers for oral carcinogenesis.

Wang, Xiang; Jiang, Wenhui; Duan, Ning; Qian, Yajie; Zhou, Qian; Ye, Pei; Jiang, Hongliu; Bai, Yang; Zhang, Weiyun; Wang, Wenmei

2014-01-01

78

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

PubMed Central

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

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

2011-01-01

79

Pharmacokinetics and effects on bowel and throat microflora of oral levofloxacin as antibacterial prophylaxis in neutropenic patients with haematological malignancies  

Microsoft Academic Search

Gram-positive breakthrough infections pose a major drawback to the use of quinolones for antibacterial prophylaxis in neutropenic patients. Levofloxacin offers the advantage of an augmented Gram-positive spectrum and may potentially overcome this problem. In an open-label, clinical pilot study, we investigated the effects on throat and bowel microflora and pharmacokinetics of a once-daily oral dose of 500 mg levofloxacin, during

G. J. Timmers; Y. Dijstelbloem; A. M. Simoons-Smit; A J van Winkelhoff; D J Touw; C. M. J. E. Vandenbroucke-Grauls; P C Huijgens

2004-01-01

80

Precancerous Stem Cells Have the Potential for both Benign and Malignant Differentiation  

Microsoft Academic Search

Cancer stem cells (CSCs) have been identified in hematopoietic and solid tumors. However, their precursors—namely, precancerous stem cells (pCSCs) —have not been characterized. Here we experimentally define the pCSCs that have the potential for both benign and malignant differentiation, depending on environmental cues. While clonal pCSCs can develop into various types of tissue cells in immunocompetent mice without developing into

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

2007-01-01

81

Chondroitin sulfate proteoglycan-4: a biomarker and a potential immunotherapeutic target for canine malignant melanoma.  

PubMed

Chondroitin sulfate proteoglycan-4 (CSPG4), also known as high molecular weight-melanoma associated antigen (HMW-MAA), is a membrane-bound chondroitin sulfate proteoglycan highly expressed by human melanoma cells. This phylogenetically conserved tumour antigen plays an important biological role in human melanoma, where it is used as a marker to diagnose forms with unusual characteristics, such as desmoplastic melanoma, and to detect melanoma cells in lymph nodes and peripheral blood, and as a target for immunotherapy because of its restricted distribution in normal tissues. To identify suitable targets to develop novel approaches of treating canine melanoma, CSPG4 was studies to see whether it is expressed in canine malignant melanomas. Immunohistochemical staining of 65 canine malignant melanomas with an anti-human CSPG4-specific antibody detected CSPG4 in 37 cases (56.9%). Positive staining was more frequent, albeit not significantly, in amelanotic compared to melanotic tumours and was statistically associated with tumours having both melanin and the epithelioid histotype. The frequency of CSPG4 expression was similar to that of other melanoma antigens used as diagnostic markers for canine malignant melanoma, such as Melan A and the protein recognized by the PNL2 monoclonal antibody. The results suggest that CSPG4 constitutes a new potential immunohistochemical marker of canine malignant melanoma and may represent an immunotherapeutic target as in humans. PMID:21482159

Mayayo, Saray Lorda; Prestigio, Simone; Maniscalco, Lorella; La Rosa, Giuseppe; Aricň, Arianna; De Maria, Raffaella; Cavallo, Federica; Ferrone, Soldano; Buracco, Paolo; Iussich, Selina

2011-11-01

82

Potential applications of oral brush cytology with liquid-based technology: results from a cohort of normal oral mucosa.  

PubMed

Fifty healthy volunteers were studied to assess the potential applications of oral brush sampling using liquid-based cytology. Three specimens from the buccal mucosa and lateral border of tongue were collected from each subject by using cervical brushes and brooms. The brush was immersed in a preservative fluid. The sample in the preservative fluid was processed according to the manufacturer's directions (SurePath, UK). Slides were stained by the Papanicolaou method and assessed for squamous cell adequacy by the same criteria used for cervical cytology screening. Immunocytochemical staining for FHIT (Fragile Histidine Triad) was applied in liquid-based preparations following the streptavidin-biotin-peroxidase method. Human papillomavirus (HPV) detection was performed using the Hybrid Capture 2 assay (Digene) and the PCR-based Roche AMPLICOR HPV Test. LBC preparation slides showed good sample preservation, specimen adequacy and visualization of cell morphology. Interestingly, nine cases showed borderline cytological abnormalities from apparently normal oral mucosa. All cases showed good quality positive FHIT immunoreactivity staining. All studied cases were high-risk HPV negative using HC2 assay method. However, the AMPLICOR Roche Test detected four samples with positive results for high-risk HPVs. Liquid-based cytology has potential as a screening tool for oral cancer and precancer. The method may also have applications for research and practice in the field of oral cancer and precancer. However a special custom-designed oral cytobrush is required. PMID:16458571

Kujan, Omar; Desai, Mina; Sargent, Alexandra; Bailey, Andrew; Turner, Andrew; Sloan, Philip

2006-09-01

83

Clinical guidelines in early detection of oral squamous cell carcinoma arising in oral lichen planus: a 5-year experience  

Microsoft Academic Search

In recent years, studies on the malignant potential of oral lichen planus (OLP) provided clinical evidence that patients affected by OLP have an increased risk to develop oral squamous cell carcinoma (OSCC); nevertheless, controversies still exist as to whether OLP has inherent predisposition to become malignant, or not. We believe extremely careful management of OLP patient is mandatory, and the

M. D. Mignogna; L. Lo Muzio; L. Lo Russo; S. Fedele; E. Ruoppo; E. Bucci

2001-01-01

84

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

Microsoft Academic Search

BACKGROUND: Despite the recently reported drop in the overall death rate from cancer, the estimated survival rate and number of deaths from oral cancer remain virtually unchanged. Early detection efforts, in combination with strategies for prevention and risk-reduction, have the potential to dramatically improve clinical outcomes. The identification of non-toxic, effective treatments, including complementary and alternative therapies, is critical if

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

2007-01-01

85

Soft Tissue Giant Cell Tumour of Low Malignant Potential: A Rare Tumour at a Rare Site  

PubMed Central

“Soft tissue giant cell tumour of low malignant potential” is considered as the soft tissue counterpart of osteoclastoma of the bone. It is a primary soft tissue tumour which is classified under the category of fibrohistiocytic tumours of intermediate malignancy.Seventy percent of the tumours involve the extremities and only about seven percent of them arise in head and neck region. They are composed of nodules of histiocytes in a vascular stroma, with multinucleated osteoclast-like giant cells positive for vimentin, smooth muscle actin (SMA), CD68 and Tarterate Resistant Acid Phosphatase (TRAP). We are presenting a case of a 75-year-old man who had a nodule on the ala of the nose. Histopathology showed a histiocytic lesion. Benign fibrous histiocytoma, plexiform fibrohistiocytic tumour, solitary reticulohistiocytoma and histioid leprosy were ruled out by using special stains and immunostains. Expression of smooth muscle actin and CD68 confirmed the diagnosis of a soft tissue giant cell tumour with a low malignant potential.

Bhat, Amoolya; V., Geethamani; C., Vijaya

2013-01-01

86

Altered Immunohistochemical Expression of Mast Cell Tryptase and Chymase in the Pathogenesis of Oral Submucous Fibrosis and Malignant Transformation of the Overlying Epithelium  

PubMed Central

Mast cells (MCs) expressing serine proteases; tryptase and chymase, are associated with fibrosis in various diseases. However, little is known about their involvement in oral submucous fibrosis (OSF). Our goal was to evaluate the role of MC tryptase and chymase in the pathogenesis of OSF and its malignant transformation. Immunohistochemical expression of MC tryptase and chymase was evaluated in 20 cases of OSF, 10 cases of oral squamous cell carcinoma (OSCC) and 10 cases of healthy controls. Subepithelial zone of Stage 1 and 2 while deep zone of Stage 3 and 4 OSF demonstrated increased tryptase positive MCs. OSCC revealed a proportionate increase in tryptase and chymase positive MCs irrespective of areas of distribution. An altered balance in the subepithelial and deep distribution of tryptase and chymase positive MCs play an important role in the pathogenesis of OSF and its malignant transformation.

Yadav, Archana; Desai, Rajiv S.; Bhuta, Bansari A.; Singh, Jatinder S.; Mehta, Reema; Nehete, Akash P.

2014-01-01

87

Oral cancer chemotherapy in paediatric patients: obstacles and potential for development and utilisation.  

PubMed

Although most cancer chemotherapy in children is administered parenterally, oral formulations are becoming increasingly available for use in patients as young as infants. Incentives for this approach include safety, flexibility, reduced financial cost, improved quality of life, and the potential for improved efficacy. The ability to deliver chemotherapy at home and apply schedules of administration that increase the agent's efficacy because patients do not require hospitalisation or visits to the clinic renders oral chemotherapy particularly attractive. Obstacles to oral chemotherapy in paediatric patients include restrictions in dose size and schedule, uncertain or low bioavailability, adverse effects of malabsorption, and adherence (noncompliance and refusal to take oral chemotherapy). Techniques to overcome most of these limitations are available or can be developed, and lack of an oral formulation can be solved in many instances by the pharmaceutical industry. Future developments in oral chemotherapy should not be limited to adult patient applications. PMID:10711852

Bleyer, W A; Danielson, M G

1999-01-01

88

Mutant p53 facilitates somatic cell reprogramming and augments the malignant potential of reprogrammed cells.  

PubMed

p53 deficiency enhances the efficiency of somatic cell reprogramming to a pluripotent state. As p53 is usually mutated in human tumors and many mutated forms of p53 gain novel activities, we studied the influence of mutant p53 (mut-p53) on somatic cell reprogramming. Our data indicate a novel gain of function (GOF) property for mut-p53, which markedly enhanced the efficiency of the reprogramming process compared with p53 deficiency. Importantly, this novel activity of mut-p53 induced alterations in the characteristics of the reprogrammed cells. Although p53 knockout (KO) cells reprogrammed with only Oct4 and Sox2 maintained their pluripotent capacity in vivo, reprogrammed cells expressing mutant p53 lost this capability and gave rise to malignant tumors. This novel GOF of mut-p53 is not attributed to its effect on proliferation, as both p53 KO and mut-p53 cells displayed similar proliferation rates. In addition, we demonstrate an oncogenic activity of Klf4, as its overexpression in either p53 KO or mut-p53 cells induced aggressive tumors. Overall, our data show that reprogrammed cells with the capacity to differentiate into the three germ layers in vitro can form malignant tumors, suggesting that in genetically unstable cells, such as those in which p53 is mutated, reprogramming may result in the generation of cells with malignant tumor-forming potential. PMID:20696700

Sarig, Rachel; Rivlin, Noa; Brosh, Ran; Bornstein, Chamutal; Kamer, Iris; Ezra, Osnat; Molchadsky, Alina; Goldfinger, Naomi; Brenner, Ori; Rotter, Varda

2010-09-27

89

COX-2 overexpression increases malignant potential of human glioma cells through Id1.  

PubMed

Increased COX-2 expression directly correlates with glioma grade and is associated with shorter survival in glioblastoma (GBM) patients. COX-2 is also regulated by epidermal growth factor receptor signaling which is important in the pathogenesis of GBMs. However, COX-2 expression has not been previously shown to directly alter malignancy of GBMs. Id1 is a member of the helix-loop-helix (HLH) family of transcriptional repressors that act as dominant-negative inhibitors of basic-HLH factors. This factor has been shown to be regulated by COX-2 in breast carcinoma cells and recent studies suggest that Id1 may also be involved in the genesis/progression of gliomas. We now show that COX-2 increases the aggressiveness of GBM cells. GBM cells with COX-2 overexpression show increased growth of colonies in soft agar. Tumorigenesis in vivo is also increased in both subcutaneous flank and orthotopic intracranial tumor models. COX-2 overexpression induces Id1 expression in two GBM cell lines suggesting a role for Id1 in glioma transformation/tumorigenesis. Furthermore, we find direct evidence of a role for Id1 with significant suppression of in vitro transformation and in vivo tumorigenesis in COX-2-overexpressing GBM cells where Id1 has been knocked down. In fact, Id1 is even more efficient at enhancing transformation/tumorigenesis of GBM cells than COX-2. Finally, GBM cells with COX-2 or Id1 overexpression show greater migration/invasive potential and tumors that arise from these cells also display increased microvessel density, results in line with the increased malignant potential seen in these cells. Thus, COX-2 enhances the malignancy of GBM cells through induction of Id1. PMID:24659686

Xu, Kaiming; Wang, Lanfang; Shu, Hui-Kuo G

2014-03-15

90

COX-2 overexpression increases malignant potential of human glioma cells through Id1  

PubMed Central

Increased COX-2 expression directly correlates with glioma grade and is associated with shorter survival in glioblastoma (GBM) patients. COX-2 is also regulated by epidermal growth factor receptor signaling which is important in the pathogenesis of GBMs. However, COX-2 expression has not been previously shown to directly alter malignancy of GBMs. Id1 is a member of the helix-loop-helix (HLH) family of transcriptional repressors that act as dominant-negative inhibitors of basic-HLH factors. This factor has been shown to be regulated by COX-2 in breast carcinoma cells and recent studies suggest that Id1 may also be involved in the genesis/progression of gliomas. We now show that COX-2 increases the aggressiveness of GBM cells. GBM cells with COX-2 overexpression show increased growth of colonies in soft agar. Tumorigenesis in vivo is also increased in both subcutaneous flank and orthotopic intracranial tumor models. COX-2 overexpression induces Id1 expression in two GBM cell lines suggesting a role for Id1 in glioma transformation/tumorigenesis. Furthermore, we find direct evidence of a role for Id1 with significant suppression of in vitro transformation and in vivo tumorigenesis in COX-2-overexpressing GBM cells where Id1 has been knocked down. In fact, Id1 is even more efficient at enhancing transformation/tumorigenesis of GBM cells than COX-2. Finally, GBM cells with COX-2 or Id1 overexpression show greater migration/invasive potential and tumors that arise from these cells also display increased microvessel density, results in line with the increased malignant potential seen in these cells. Thus, COX-2 enhances the malignancy of GBM cells through induction of Id1.

Xu, Kaiming; Wang, Lanfang; Shu, Hui-Kuo G.

2014-01-01

91

Satellite DNA hypomethylation vs. overall genomic hypomethylation in ovarian epithelial tumors of different malignant potential.  

PubMed

Rearrangements in heterochromatin in the vicinity of the centromeres of chromosomes 1 and 16 are frequent in many types of cancer, including ovarian epithelial carcinomas. Satellite 2 DNA is the main sequence in the unusually long heterochromatin region adjacent to the centromere of each of these chromosomes. Rearrangements in these regions and hypomethylation of satellite 2 DNA are a characteristic feature of patients with a rare recessive genetic disease, ICF (immunodeficiency, centromeric region instability, and facial anomalies). In all normal tissues of postnatal somatic origin, satellite 2 DNA is highly methylated. We examined satellite 2 DNA methylation in ovarian tumors of different malignant potential, namely, ovarian cystadenomas, low malignant potential (LMP) tumors, and epithelial carcinomas. Most of the carcinomas and LMP tumors exhibited hypomethylation in satellite 2 DNA of both chromosomes 1 and 16. A comparison of methylation of these sequences in the three types of ovarian neoplasms demonstrated that there was a statistically significant correlation between the extent of this satellite DNA hypomethylation and the degree of malignancy (P<0.01). Also, there was a statistically significant association (P<0.005) between genome-wide hypomethylation and undermethylation of satellite 2 DNA among these 17 tumors. In addition, we found abnormal hypomethylation of satellite alpha DNA in the centromere of chromosome 1 in many of these tumors. Our findings are consistent with the hypothesis that one of the ways that genome-wide hypomethylation facilitates tumor development is that it often includes satellite hypomethylation which might predispose cells to structural and numerical chromosomal aberrations. Several of the proteins that bind to pericentromeric heterochromatin are known to be sensitive to the methylation status of their target sequences and so could be among the sensors for detecting abnormal demethylation and mediating effects on chromosome structure and stability. PMID:10029684

Qu, G; Dubeau, L; Narayan, A; Yu, M C; Ehrlich, M

1999-01-25

92

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

PubMed

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

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

2007-01-01

93

Precancerous Stem Cells Have the Potential for both Benign and Malignant Differentiation  

PubMed Central

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

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

2007-01-01

94

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

PubMed Central

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

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

2013-01-01

95

Potential antidotes for reversal of old and new oral anticoagulants.  

PubMed

The prescription of new oral anticoagulants is on the rise. As opposed to vitamin K antagonists and heparins the new agents have single targets in the coagulation cascade, more predictable pharmacokinetics and they lack validated and available antidotes. In general, the new agents have similar or lower bleeding risk than vitamin K antagonists, especially risk of intracranial bleeding. Risk factors for bleeding are typically the same for old and new anticoagulants. Old age, renal dysfunction and concomitant antiplatelet agents seem to be recurring risk factors. Adequate supportive care and temporary removal of all antithrombotic agents constitute the basis for management of serious bleeding complications. With the exception of vitamin K (for vitamin K antagonists) and protamine (for heparin) the same array of prohemostatic agents - unactivated or activated prothrombin complex concentrate, and activated factor VIIa - have been tried for almost all anticocoagulants in different models, and for some agents also in patients, with varying success. Hemodialysis can reduce the level of dabigatran efficiently and activated charcoal may be used for very recent oral ingestion of lipophilic agents. In view of the shorter half life of the new agents compared to warfarin the need for reversal agents may be less critical. Nevertheless, highly specific reversal agents for the thrombin- and factor Xa-inhibitors are under development and might be available within two years. © 2014 Elsevier Ltd. All rights reserved. PMID:24862137

Suryanarayan, Deepa; Schulman, Sam

2014-05-01

96

Immunohistochemical profiling of benign, low malignant potential and low grade serous epithelial ovarian tumors  

PubMed Central

Background Serous epithelial ovarian tumors can be subdivided into benign (BOV), low malignant potential (LMP) or borderline and invasive (TOV) tumors. Although the molecular characteristics of serous BOV, LMP and low grade (LG) TOV tumors has been initiated, definitive immunohistochemical markers to distinguish between these tumor types have not been defined. Methods In the present study, we used a tissue array composed of 27 BOVs, 78 LMPs and 23 LG TOVs to evaluate the protein expression of a subset of selected candidates identified in our previous studies (Ape1, Set, Ran, Ccne1 and Trail) or known to be implicated in epithelial ovarian cancer disease (p21, Ccnb1, Ckd1). Results Statistically significant difference in protein expression was observed for Ccnb1 when BOV tumors were compared to LMP tumors (p = 0.003). When BOV were compared to LG TOV tumors, Trail was significantly expressed at a higher level in malignant tumors (p = 0.01). Expression of p21 was significantly lower in LG tumors when compared with either BOVs (p = 0.03) or LMPs (p = 0.001). We also observed that expression of p21 was higher in LMP tumors with no (p = 0.02) or non-invasive (p = 0.01) implants compared to the LMP associated with invasive implants. Conclusion This study represents an extensive analyse of the benign and highly differentiated ovarian disease from an immunohistochemical perspective.

Ouellet, Veronique; Ling, Tak Hay; Normandin, Karine; Madore, Jason; Lussier, Christian; Barres, Veronique; Bachvarov, Dimcho; Rancourt, Claudine; Tonin, Patricia N; Provencher, Diane M; Mes-Masson, Anne-Marie

2008-01-01

97

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

PubMed Central

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.

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

2009-01-01

98

Oral tongue cancer gene expression profiling: Identification of novel potential prognosticators by oligonucleotide microarray analysis  

Microsoft Academic Search

BACKGROUND: The present study is aimed at identifying potential candidate genes as prognostic markers in human oral tongue squamous cell carcinoma (SCC) by large scale gene expression profiling. METHODS: The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Patients (n=20) from which there were available tumor and matched normal mucosa

Cherry L Estilo; Pornchai O-charoenrat; Simon Talbot; Nicholas D Socci; Diane L Carlson; Ronald Ghossein; Tijaana Williams; Yoshihiro Yonekawa; Yegnanarayana Ramanathan; Jay O Boyle; Dennis H Kraus; Snehal Patel; Ashok R Shaha; Richard J Wong; Joseph M Huryn; Jatin P Shah; Bhuvanesh Singh

2009-01-01

99

Transforming growth factor-alpha, epidermal growth factor receptor, and proliferating potential in benign and malignant gliomas.  

PubMed

Surgical specimens from six benign and 16 malignant human gliomas were investigated immunohistochemically to correlate the degree of malignancy, the distribution of transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) receptor, and the potential for cell proliferation using monoclonal antibodies to TGF-alpha, EGF receptor, and Ki-67. Fourteen (88%) of the malignant gliomas and one (17%) of the benign gliomas were found to be positive for TGF-alpha, and 14 (88%) of the malignant gliomas and two (33%) of the benign gliomas expressed EGF receptor. The proliferation index with Ki-67 was 18.8% +/- 8.1% (mean +/- standard deviation) in malignant gliomas and 1.9% +/- 1.8% in benign gliomas. In general, cells positive for EGF receptor and Ki-67 were randomly distributed throughout the tumor tissue, and cells positive for TGF-alpha tended to be clustered without obvious relationship to areas of necrosis or blood vessels. In some tumors, cells positive for TGF-alpha, EGF receptor, and Ki-67 were associated in a focal distribution. The more frequent expression of TGF-alpha and EGF receptor in the highly proliferative malignant gliomas is compatible with a role for TGF-alpha and EGF receptor in the induction or stimulation of malignant gliomas. PMID:2045927

Maruno, M; Kovach, J S; Kelly, P J; Yanagihara, T

1991-07-01

100

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

PubMed Central

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

TODA, MITSUNORI; KAWAMOTO, TERUYA; UEHA, TAKESHI; KISHIMOTO, KENTA; HARA, HITOMI; FUKASE, NAOMASA; ONISHI, YASUO; HARADA, RISA; MINODA, MASAYA; KUROSAKA, MASAHIRO; AKISUE, TOSHIHIRO

2013-01-01

101

p16INK4A Immunohistochemical Overexpression in Premalignant and Malignant Oral Lesions Infected with Human Papillomavirus  

Microsoft Academic Search

Human papillomavirus (HPV) is believed to promote the oncogenic process, and the correlation between viral oncoproteins and dysfunction of p16INK4A tumor suppressor protein in oral lesions is controversial. To test the hypothesis that anogenital HPV types participate in disruption of the regulation of p16INK4A suppressor protein in oral lesions, we analyzed 46 oral biopsy specimens for the presence of HPV

Paula Andrea Gabrielli Fregonesi; Debora Barreto Teresa; Roberta Aparecida Duarte; Carlos Benatti Neto; Maria Rita Brancini de Oliveira; Christiane Pienna Soares

2003-01-01

102

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

PubMed Central

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

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

2009-01-01

103

[Involvement of zinc in taste disturbance occurring during treatment for malignant tumor in the chest and the effects of polaprezinc oral disintegrating tablets (a retrospective study)].  

PubMed

We analyzed the correlation between serum zinc levels and taste disturbance, and between patient backgrounds and serum zinc levels or taste disturbance, and evaluated the effects of polaprezinc oral disintegrating tablets on taste disturbance in 29 patients with lung cancer and one patient with malignant pleural mesothelioma who were receiving chemotherapy. Taste disturbance developed in 11 (36.7%) out of 30 patients. Serum zinc levels significantly correlated with taste disturbance (p=0.0227). Serum zinc levels were significantly lower (p=0.0235) and taste disturbance tended to be more frequent (p=0.0625) in males. Polaprezinc improved taste disturbance in 5 of 8 patients. PMID:18633224

Nakata, Yoko; Hirashima, Tomonori; Kondou, Yoko; Tokuoka, Yoshie; Imazato, Hitomi; Iwata, Kaori; Oomori, Yukari; Yamato, Akihiro; Shimizu, Saburou; Nagao, Sadako; Matsui, Kaoru; Abe, Noriko

2008-06-01

104

The growth potential of ependymomas with varying grades of malignancy measured by the Ki-67 labelling index and mitotic index.  

PubMed

The prognostic significance of histopathological grade for postoperative outcome is not yet known for ependymomas. Data on proliferation kinetics of these tumors are few. In our study, the growth fraction was immunohistochemically determined by labelling cell nuclei with the monoclonal antibody Ki-67 in 24 tumors of the ependymoma group (2 malignant ependymomas grade III, 11 ependymomas grade II, 8 spinal ependymomas, and 3 subependymomas). The results were compared with the mitotic index in the same tumor areas. Both growth parameters are related to the grade of malignancy. The differences between the results of spinal ependymomas (grade I) and of intracranial tumors (grade II) were statistically significant. Malignant ependymomas had the highest values. Variable growth potentials could be demonstrated in a few tumors. A non-linear relationship between growth fraction and mitotic index was found, indicating a variable generation time in ependymomas (as in astrocytomas). Thus, with rising grade of malignancy the growth fraction increases and the generation time decreases. PMID:8345908

Schröder, R; Ploner, C; Ernestus, R I

1993-01-01

105

A standard picture of healthy oral mucosae by direct oral microscopy  

PubMed Central

Introduction Direct oral microscopy constitutes a novel technique of in vivo oral mucosae examination. The basic principles of this method derive from colposcopy and dermoscopy. The main goal of direct oral microscopy is the earliest possible detection of oral precancerous lesions in order to implement their treatment as quickly as possible and prevent malignant transformation. Aim To establish a standard picture of healthy oral mucosae with direct oral microscopy applying standard colposcopic criteria in order to create a reference point for further diagnosis of precancerous lesions. Material and methods Thirty patients of both genders with clinically unaltered oral mucosae were examined. For every individual, clinical examination with the naked eye was performed, followed by direct oral microscopy with colposcopic assessment criteria. Oral mucosae at various sites (lip, cheek, floor of mouth, ventral and lateral sides of the tongue, alveolar ridge and soft palate) were examined. Results Subepithelial blood vessel patterns, mucosal surface, colour tone and transparency were described for healthy oral mucosae. Moreover, cases with clinically unaltered oral mucosae where direct oral microscopy revealed subclinical alterations were described. Conclusions Direct oral microscopy with colposcopic assessment criteria enables establishment of a repeated picture of unaltered oral mucosae. The standard picture of healthy oral mucosae is an essential reference point for application of this technique to early diagnose potentially malignant oral mucosal lesions as well as apply their early treatment.

Drogoszewska, Barbara; Michcik, Adam; Polcyn, Adam

2013-01-01

106

First-in-Human Phase 0 Trial of Oral 5-iodo-2-pyrimidinone-2?-deoxyribose (IPdR) in Patients with Advanced Malignancies  

PubMed Central

Purpose Iododeoxyuridine (IdUrd), a halogenated nucleoside analog, produced clinical responses when administered as a radiosensitizer via continuous intravenous (c.i.v.) infusion over the course of radiation therapy. We conducted a Phase 0 trial of 5-iodo-2-pyrimidinone-2?-deoxyribose (IPdR), an oral prodrug of IdUrd, in patients with advanced malignances to assess whether the oral route was a feasible alternative to c.i.v. infusion prior to embarking on large-scale clinical trials. Plasma concentrations of IPdR, IdUrd, and other metabolites were measured after a single oral dose of IPdR. Patients and Methods Eligible patients had advanced refractory malignancies. A single oral dose of IPdR was administered per patient and patients were followed for 14 days for safety assessments; dose escalations were planned (150, 300, 600, 1200, and 2400 mg) with one patient per dose level (DL) and 6 patients at the highest DL. Blood sampling was performed over a 24-hour period for pharmacokinetic analysis. Results There were no drug-related adverse events. Plasma concentrations of IdUrd generally increased as the dose of IPdR escalated from 150 to 2400 mg. All patients at the 2400 mg dose achieved peak IdUrd levels of (mean ± SD) 4.0 ?M ± 1.02 ?M (25% CV) at 1.67 ± 1.21 hours after IPdR administration. Conclusions Adequate plasma levels of IdUrd were obtained to justify proceeding with a Phase I trial of IPdR in combination with radiation. This trial demonstrates the ability of a small, Phase 0 study to provide critical information for decision-making regarding future development of a drug.

Kummar, Shivaani; Anderson, Larry; Hill, Kimberly; Majerova, Eva; Allen, Deborah; Horneffer, Yvonne; Ivy, S. Percy; Rubinstein, Larry; Harris, Pamela; Doroshow, James H.; Collins, Jerry M.

2013-01-01

107

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

PubMed Central

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.

Taichman, L. Susan; Havens, Aaron M.

2012-01-01

108

Expression of ?-taxilin in hepatocellular carcinoma correlates with growth activity and malignant potential of the tumor.  

PubMed

The membrane traffic system has been recognized to be involved in carcinogenesis and tumor progression in several types of tumors. ?-taxilin is a newly identified membrane traffic-related molecule, and its up-regulation has been reported in embryonic and malignant tissues of neural origin. In the present study, we analyzed the expression of ?-taxilin in relation to clinicopathological features of hepatocellular carcinomas (HCC) and proliferative activity of the tumor determined by proliferating cell nuclear antigen labeling index (PCNA-LI). Twenty-nine surgically resected nodules of HCC (8 well-, 11 moderately-, and 10 poorly-differentiated) were studied. Fifteen cases showed 'strong staining', while 14 cases showed 'weak staining' for ?-taxilin. A significantly higher expression of ?-taxilin was observed in less-differentiated (p=0.005), and more invasive (p=0.016) HCCs. The 'strong staining' group showed significantly higher PCNA-LI than the 'weak staining' group (the medians of PCNA-LI were 59.4% vs. 14.4%, p<0.0001). We also evaluated the expression of ?-taxilin in hepatoma cell lines (PLC/PRF/5, Hep G2 and HuH-6) in association with cell proliferation. The expression levels of ?-taxilin protein were correlated with their growth rates. In conclusion, the expression of the ?-taxilin protein was related with an increased proliferative activity and a less-differentiated histological grade of HCC. ?-taxilin may be involved in cell proliferation of HCC, and its expression can be a marker of malignant potential of HCC. PMID:21042709

Ohtomo, Natsuko; Tomiya, Tomoaki; Tanoue, Yasushi; Inoue, Yukiko; Nishikawa, Takako; Ikeda, Hitoshi; Seyama, Yasuji; Kokudo, Norihiro; Shibahara, Junji; Fukayama, Masashi; Koike, Kazuhiko; Shirataki, Hiromichi; Fujiwara, Kenji

2010-12-01

109

Genes and oral cancer  

PubMed Central

Oral cancers have been one of the leading causes of deaths particularly in the developing countries. Prime reason for this high mortality and morbidity is attributed to the delay in diagnosis and prompt treatment. Relentless research in the field of oncology has led to the advent of novel procedures for the early detection of oral cancers. Molecular biology is highly promising in this regard. It is a procedure that detects alterations at a molecular level much before they are seen under a microscope and much before clinical changes occur. Molecular studies serve as the basis by which we will eventually be able not only to augment clinical assessment and classification of oral lesions but also predict malignant potential of oral lesions, thus reducing the incidence and increasing the scope for early diagnosis and treatment of oral cancers. However, making such sophisticated tools available for the common man in developing countries is one of the most important challenges faced today.

Jurel, Sunit Kumar; Gupta, Durga Shanker; Singh, Raghuwar D.; Singh, Mrinalini; Srivastava, Shilpi

2014-01-01

110

Novel 2-Aminobenzamides as Potential Orally Active Antithrombotic Agents  

PubMed Central

In an effort to develop potent antithrombotic agents, a series of novel 2-aminobenzamide derivatives were synthesized and screened for their in vivo antithrombotic activity. Among the 23 compounds tested, compound (8g) showed the most promising antithrombotic activity, which was comparable with clinically used aspirin or warfarin, but at variance with these standard drugs, 8g did not exhibit the increased bleeding time, suggesting its potential as a novel antithrombotic agent.

2012-01-01

111

Proliferative potential of malignant glioma cells before and after interstitial brachytherapy.  

PubMed

The viability of tumor cells in radionecrotic tissue after interstitial brachytherapy (BRTX) was evaluated using immunohistochemical markers of proliferative potential in primary and recurrent tumors. Tumor specimens from 30 patients with malignant gliomas (14 anaplastic astrocytomas, 16 glioblastomas) taken before and after BRTX were examined using MIB-1 monoclonal antibody. Histological examination of specimens obtained by craniotomy or stereotactic biopsy after BRTX revealed tumor recurrence in 18 patients and radionecrosis in 12 patients including two with pure radionecrosis and 10 with a mixture of both tumor and radionecrosis. The MIB-1 index of the tumors with radionecrosis was 7.6 +/- 5.5%, and that of the primary tumors was 17.0 +/- 11.2%, showing a significant difference (p < 0.05). There was no significant difference between the MIB-1 index of the primary tumors with local recurrence after BRTX and the primary tumors which underwent radionecrosis. Although morphologically viable tumor cells were found in the radionecrotic tissue, BRTX causes a reduction in the proliferative potential of these tumor cells. PMID:10481436

Kunishio, K; Matsumoto, K; Higashi, H; Adachi, H; Tamiya, T; Furuta, T; Ohmoto, T

1999-05-01

112

Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs  

PubMed Central

Background: Potential drug–drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment. Methods: A search was conducted in a computer-based medication prescription system for dispensing oral anticancer drugs to outpatients in three Dutch centres. Potential drug–drug interactions were identified using electronic (Drug Interaction Fact software) and manual screening methods (peer-reviewed reports). Results: In the 898 patients included in the study, 1359 PDDIs were identified in 426 patients (46%, 95% confidence interval (CI)=42–50%). In 143 patients (16%), a major PDDI was identified. The drug classes most frequently involved in a major PDDI were coumarins and opioids. The majority of cases concerned central nervous system interactions, PDDIs that can cause gastrointestinal toxicity and prolongation of QT intervals. In multivariate analysis, concomitant use of more drugs (odds ratio (OR)=1.66, 95% CI=1.54–1.78, P<0001) and genito-urinary cancer (OR=0.25, 95% CI=0.12–0.52, P<0001) were risk factors. Conclusion: Potential drug–drug interactions are very common among cancer patients on oral cancer therapy. Physicians and pharmacists should be more aware of these potential interactions.

van Leeuwen, R W F; Brundel, D H S; Neef, C; van Gelder, T; Mathijssen, R H J; Burger, D M; Jansman, F G A

2013-01-01

113

POTENTIAL LONG-TERM TOXICITY OF REPEATED ORALLY ADMINISTERED DOSES OF ARTEMETHER IN RATS  

Microsoft Academic Search

Artemether, an efficacious antimalarial drug, effectively prevents patent schistosome infections and morbidity, as established in laboratory models and in clinical trials. In view of concern about the potential long-term toxicity, rats were treated orally with 80 mg\\/kg artemether once every 2 weeks for 5 months. After the final treatment, routine blood test results were normal except for reversible reductions of

XIAO SHUHUA; YANG YUANQING; JURG UTZINGER; GUO HUIFANG; JIAO PEIYING; MEI JINYING; GUO JIAN; ROBERT BERGQUIST; MARCEL TANNER

114

The discovery of potent, selective, and orally bioavailable PDE9 inhibitors as potential hypoglycemic agents.  

PubMed

Starting from a non-selective pyrazolo-pyrimidone lead, the sequential use of parallel medicinal chemistry and directed synthesis led to the discovery of potent, highly selective, and orally bioavailable PDE9 inhibitors. The availability of these tools allowed for a thorough evaluation of the therapeutic potential of PDE9 inhibition. PMID:19339180

Deninno, Michael P; Andrews, Melissa; Bell, Andrew S; Chen, Yue; Eller-Zarbo, Cynthia; Eshelby, Nan; Etienne, John B; Moore, Dianna E; Palmer, Michael J; Visser, Michael S; Yu, Li J; Zavadoski, William J; Michael Gibbs, E

2009-05-01

115

The discovery of potent, selective, and orally bioavailable PDE9 inhibitors as potential hypoglycemic agents  

Microsoft Academic Search

Starting from a non-selective pyrazolo-pyrimidone lead, the sequential use of parallel medicinal chemistry and directed synthesis led to the discovery of potent, highly selective, and orally bioavailable PDE9 inhibitors. The availability of these tools allowed for a thorough evaluation of the therapeutic potential of PDE9 inhibition.

Michael P. DeNinno; Melissa Andrews; Andrew S. Bell; Yue Chen; Cynthia Eller-Zarbo; Nan Eshelby; John B. Etienne; Dianna E. Moore; Michael J. Palmer; Michael S. Visser; Li J. Yu; William J. Zavadoski; E. Michael Gibbs

2009-01-01

116

A Phase I study of the oral antimetabolite, CS-682, administered once daily 5 days per week in patients with refractory solid tumor malignancies.  

PubMed

The development of nucleoside analogues has had a major impact on cancer therapy. CS-682 is a novel, orally administered nucleoside analogue with a unique mechanism of action. CS-682 undergoes conversion to the active metabolite, CNDAC, which then leads to the inhibition of DNA polymerase and a novel "DNA self-strand breaking mechanism." We conducted a Phase I study of CS-682, administered orally five days per week in patients with refractory solid tumor malignancies. Forty-eight patients were enrolled on study. The recommended phase II dose of 30 mg/m(2) given orally once daily for 5 days a week for 4 weeks followed by 2 weeks off drug, was well tolerated. The most common dose limiting toxicity was neutropenia, which occurred at the highest dose levels of CS-682. This was correlated with higher CNDAC Cmax and AUC values. No tumor responses were noted in this heavily pretreated population. However, given the ease of administration and tolerability, further investigation of this agent is warranted. PMID:16788861

Gilbert, Jill; Carducci, Michael A; Baker, Sharyn D; Dees, Elizabeth C; Donehower, Ross

2006-11-01

117

Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma  

PubMed Central

Ribonucleases are a superfamily of enzymes which operate at the crossroads of transcription and translation, catalyzing the degradation of RNA; they can be cytotoxic because the cleavage of RNA renders indecipherable its information. Ranpirnase is a novel ribonuclease which preferentially degrades tRNA, thus leading to inhibition of protein synthesis and, ultimately, to cytostasis and cytotoxicity. Ranpirnase has demonstrated antitumor activity both in vitro and in vivo in several tumor models. The maximum tolerated dose emerging from phase I studies was 960 g/m2, with renal toxicity as the main dose-limiting toxicity. A large phase II trial showed that ranpirnase has disease-modifying activity against malignant mesothelioma. Ranpirnase proved to be superior to doxorubicin in a phase III trial, while preliminary results of another large, phase III trial, suggest that the combination of ranpirnase and doxorubicin could be more effective than doxorubicin alone. In all the above studies, ranpirnase seems to act mainly as a cytostatic rather than a cytotoxic drug, stabilizing progressive disease and potentially prolonging patients’ survival. Ranpirnase may thus find its niche in combination with doxorubicin for mesothelioma as a second-line therapy, where no standard of care presently exists.

Porta, Camillo; Paglino, Chiara; Mutti, Luciano

2008-01-01

118

Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma.  

PubMed

Ribonucleases are a superfamily of enzymes which operate at the crossroads of transcription and translation, catalyzing the degradation of RNA; they can be cytotoxic because the cleavage of RNA renders indecipherable its information. Ranpirnase is a novel ribonuclease which preferentially degrades tRNA, thus leading to inhibition of protein synthesis and, ultimately, to cytostasis and cytotoxicity. Ranpirnase has demonstrated antitumor activity both in vitro and in vivo in several tumor models. The maximum tolerated dose emerging from phase I studies was 960 g/m(2), with renal toxicity as the main dose-limiting toxicity. A large phase II trial showed that ranpirnase has disease-modifying activity against malignant mesothelioma. Ranpirnase proved to be superior to doxorubicin in a phase III trial, while preliminary results of another large, phase III trial, suggest that the combination of ranpirnase and doxorubicin could be more effective than doxorubicin alone. In all the above studies, ranpirnase seems to act mainly as a cytostatic rather than a cytotoxic drug, stabilizing progressive disease and potentially prolonging patients' survival. Ranpirnase may thus find its niche in combination with doxorubicin for mesothelioma as a second-line therapy, where no standard of care presently exists. PMID:19707441

Porta, Camillo; Paglino, Chiara; Mutti, Luciano

2008-12-01

119

Transient receptor potential canonical channels are essential for chemotactic migration of human malignant gliomas.  

PubMed

The majority of malignant primary brain tumors are gliomas, derived from glial cells. Grade IV gliomas, Glioblastoma multiforme, are extremely invasive and the clinical prognosis for patients is dismal. Gliomas utilize a number of proteins and pathways to infiltrate the brain parenchyma including ion channels and calcium signaling pathways. In this study, we investigated the localization and functional relevance of transient receptor potential canonical (TRPC) channels in glioma migration. We show that gliomas are attracted in a chemotactic manner to epidermal growth factor (EGF). Stimulation with EGF results in TRPC1 channel localization to the leading edge of migrating D54MG glioma cells. Additionally, TRPC1 channels co-localize with the lipid raft proteins, caveolin-1 and ?-cholera toxin, and biochemical assays show TRPC1 in the caveolar raft fraction of the membrane. Chemotaxis toward EGF was lost when TRPC channels were pharmacologically inhibited or by shRNA knockdown of TRPC1 channels, yet without affecting unstimulated cell motility. Moreover, lipid raft integrity was required for gliomas chemotaxis. Disruption of lipid rafts not only impaired chemotaxis but also impaired TRPC currents in whole cell recordings and decreased store-operated calcium entry as revealed by ratiomeric calcium imaging. These data indicated that TRPC1 channel association with lipid rafts is essential for glioma chemotaxis in response to stimuli, such as EGF. PMID:21506118

Bomben, Valerie C; Turner, Kathryn L; Barclay, Tia-Tabitha C; Sontheimer, Harald

2011-07-01

120

Transient Receptor Potential Canonical Channels Are Essential for Chemotactic Migration of Human Malignant Gliomas  

PubMed Central

The majority of malignant primary brain tumors are gliomas, derived from glial cells. Grade IV gliomas, Glioblastoma multiforme, are extremely invasive and the clinical prognosis for patients is dismal. Gliomas utilize a number of proteins and pathways to infiltrate the brain parenchyma including ion channels and calcium signaling pathways. In this study, we investigated the localization and functional relevance of transient receptor potential canonical (TRPC) channels in glioma migration. We show that gliomas are attracted in a chemotactic manner to epidermal growth factor (EGF). Stimulation with EGF results in TRPC1 channel localization to the leading edge of migrating D54MG glioma cells. Additionally, TRPC1 channels co-localize with the lipid raft proteins, caveolin-1 and ?-cholera toxin, and biochemical assays show TRPC1 in the caveolar raft fraction of the membrane. Chemotaxis toward EGF was lost when TRPC channels were pharmacologically inhibited or by shRNA knockdown of TRPC1 channels, yet without affecting unstimulated cell motility. Moreover, lipid raft integrity was required for gliomas chemotaxis. Disruption of lipid rafts not only impaired chemotaxis but also impaired TRPC currents in whole cell recordings and decreased store-operated calcium entry as revealed by ratiomeric calcium imaging. These data indicated that TRPC1 channel association with lipid rafts is essential for glioma chemotaxis in response to stimuli, such as EGF.

Bomben, Valerie C.; Turner, Kathryn L.; Barclay, Tia-tabitha C.; Sontheimer, Harald

2013-01-01

121

Expression of Potential Cancer Stem Cell Marker ABCG2 is Associated with Malignant Behaviors of Hepatocellular Carcinoma  

PubMed Central

Background. Despite improvement in treatment, the prognosis of hepatocellular carcinoma (HCC) remains disastrous. Cancer stem cells (CSCs) may be responsible for cancer malignant behaviors. ATP-binding cassette, subfamily G, member 2 (ABCG2) is widely expressed in both normal and cancer stem cells and may play an important role in cancer malignant behaviors. Methods. The expression of ABCG2 in HCC tissues and SMMC-7721 cells was examined, and the relevance of ABCG2 expression with clinical characteristics was analyzed. ABCG2+ and ABCG2? cells were sorted, and the potential of tumorigenicity was determined. Expression level of ABCG2 was manipulated by RNA interference and overexpression. Malignant behaviors including proliferation, drug resistance, migration, and invasion were studied in vitro. Results. Expression of ABCG2 was found in a minor group of cells in HCC tissues and cell lines. ABCG2 expression showed tendencies of association with unfavorable prognosis factors. ABCG2 positive cells showed a superior tumorigenicity. Upregulation of ABCG2 enhanced the capacity of proliferation, doxorubicin resistance, migration, and invasion potential, while downregulation of ABCG2 significantly decreased these malignant behaviors. Conclusion. Our results indicate that ABCG2 is a potential CSC marker for HCC. Its expression level has a close relationship with tumorigenicity, proliferation, drug resistance, and metastasis ability.

Luo, Weihuan; Jiao, Hongbo; Jiang, Chunping

2013-01-01

122

The value of minimal access surgery in the staging of patients with potentially resectable peripancreatic malignancy.  

PubMed Central

OBJECTIVE: The purpose of this study was to determine if an endosurgical approach that mimics open exploration would improve the accuracy of simple diagnostic laparoscopy. SUMMARY BACKGROUND DATA; Most patients with peripancreatic malignancy are found at exploration to be unable to undergo resection. Laparoscopy has been suggested as a sensitive method for detecting metastatic disease in this group of patients. However, the ability to assess resectability with simple diagnostic laparoscopy remains relatively low (<40%). METHODS: Between December 1992 and August 1994, 115 patients with radiologically resectable peripancreatic tumors underwent extended laparoscopy before undergoing a planned curative resection. This technique required assessment of the peritoneal cavity, liver, lesser sac, porta hepatis, duodenum, transverse mesocolon, and celiac and portal vessels. RESULTS: Sixty male and 55 female patients were included in the current study. The pancreatic head was involved in 74 patients (64%), followed by the body in 21 (18%), tail in 8 (7%), ampulla in 8 (7%), duodenum in 3 (3%), and distal bile duct in 1 (1%). An abdominal computed tomography (CT) scan was performed for all patients before laparoscopy, ultrasonography for 74 patients (64%), endoscopic retrograde choleangiopancreatography for 59 patients (51%), and mesenteric angiography for 9 patients (8%). Pneumoperitoneum was established successfully in all but 2 cases (98%). A complete examination of 108 patients was performed. Sixty-seven patients were considered to have resectable disease, and 61 resections were performed. Laparoscopy failed to identify hepatic metastases in 5 patients and portal venous encasement in 1 patient. Unresectable disease was identified in 41 patients. Hepatic metastases were observed in 20 patients, mesenteric vascular encasement in 14, extrapancreatic/peritoneal involvement in 16, and celiac or portal lymphatic metastases in 8. There were no intraoperative or postoperative complications related to the laparoscopic procedure. The positive predictive index, negative predictive index, and accuracy of laparoscopy were 100%, 91%, and 94%, respectively. CONCLUSIONS: This study demonstrates that extended laparoscopy is accurate and safe and makes exploration unnecessary in many patients with potentially resectable peripancreatic malignancy. In this series, 76% of patients explored were resected, compared with the authors' experience between 1983 and 1993 of 35%. The authors believe that laparoscopy is an important component in the staging of this group of patients and should be performed before exploration.

Conlon, K C; Dougherty, E; Klimstra, D S; Coit, D G; Turnbull, A D; Brennan, M F

1996-01-01

123

Cancer of the oral cavity and pharynx in Karachi--identification of potential risk factors.  

PubMed

The objective of the study was to provide an overview of the demographics of cancer of the oral cavity and pharynx in Karachi South (1995-2001), and identify potential risk factors. Cases recorded for Karachi South, at Karachi Cancer Registry during 1(st) January 1995 to 31(st) December 2002 were analysed. For maximum completion of data cancer cases, recorded from 1(st) January 1995 to 31(st) December 2001 were included for final analysis. The age standardized incidence rates per 100000 population (ASIRs) for cancer of the oral cavity (excluding salivary gland) in Karachi South were 17.1 and 16.5 in males and females whereas the ASIRs for cancer of the pharynx (excluding nasopharynx) were 7.1 and 2.4 in males and females, respectively. The oral pharyngeal ratios were 2.4 and 6.9 for males and females and gender ratios (M F) were 1.04 for the oral cavity and 3.0 for the pharynx. The mean ages were 51 years (95% CI 49.6; 52.2) and 56.1 years (95% CI 54.4; 57.8) respectively. Cancer of the oral cavity ranked 2(nd) in Karachi in both genders. Cancer of the pharynx ranked 7(th) in males and 14(th) in females. Approximately 97% of the oral cavity and pharyngeal cancers were histologically confirmed. The majority of the oral (47.1%) and pharyngeal (51.9%) cancer cases presented as grade II lesions, and were discovered at advanced stages. Of the cancers reported during 1995-2001, 60.4% of the oral and 78.1% of the pharyngeal lesions had spread to a distant site at the time of diagnosis. Squamous cell carcinoma comprised 96.5% and 91.8% of the totals. The incidences of these cancers are comparable to the highest risk regions of the world. As distinct from other geographical areas oral cancer is as common in females as in males, which may reflect the pattern of exposure to known risk factors such as betal quid, arecanut and tobacco and the absence of alcohol as a risk factor in both genders. Apergillus contamination of arecanut could also be a risk factor but no confirmation studies or quantification is available. Despite the common risk factors, incidence of pharyngeal cancer is three times higher in men as compared with women. The keys to reducing the incidence and mortality due to oral and pharyngeal cancers are prevention and control, emphasizing cessation of tobacco use and cancer screening. However a targeted cancer and tobacco control program does not presently exist in Pakistan. PMID:12875625

Bhurgri, Yasmin; Bhurgri, Asif; Hussainy, Akbar Shah; Usman, Ahmed; Faridi, Naveen; Malik, Jawaid; Zaidi, Zubair Ahmed; Muzaffar, Suhail; Kayani, Naila; Pervez, Shahid; Hasan, Sheema H

2003-01-01

124

Potential application of temozolomide in mesenchymal stem cell-based TRAIL gene therapy against malignant glioma.  

PubMed

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

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

2014-02-01

125

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

The present study aimed to demonstrate the features of fluorine-18-labeled boronophenylalanine positron emission tomography ((18)F-BPA-PET) to reveal oral cancer, as well as normal structures in the oral and maxillofacial regions. We analyzed (18)F-BPA-PET findings from 8 patients with histologically confirmed recurrent and/or advanced oral cancer scheduled for boron neutron capture therapy. The capacity of (18)F-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. (18)F-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

Ariyoshi, Yasunori; Shimahara, Masashi; Kimura, Yoshihiro; Ito, Yuichi; Shimahara, Takeshi; Miyatake, Shin-Ichi; Kawabata, Shinji

2011-05-01

126

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

PubMed Central

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

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

2011-01-01

127

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

SciTech Connect

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.

Elting, Linda S. [Section of Health Services Research, Department of Biostatistics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)]. E-mail: lelting@mdanderson.org; Cooksley, Catherine D. [Section of Health Services Research, Department of Biostatistics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Chambers, Mark S. [Department of Dental Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Garden, Adam S. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)

2007-07-15

128

Neoplasms associated with paraneoplastic pemphigus: a review with emphasis on non-hematologic malignancy and oral mucosal manifestations  

Microsoft Academic Search

The review included 163 cases of paraneoplastic pemphigus (PNP) reported between 1990 and 2003, including a new unique case of PNP associated with occult breast cancer and an ovarian cyst of borderline malignancy.Hematologic-related neoplasms or disorders were associated with 84% of the cases, with non-Hodgkin lymphoma (38.6%) as the most frequent, followed by chronic lymphocytic leukemia (18.4%) and Castleman's disease

Ilana Kaplan; Emmilia Hodak; Lehavit Ackerman; Daniel Mimouni; Grant J Anhalt; Shlomo Calderon

2004-01-01

129

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

Microsoft Academic Search

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

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

2001-01-01

130

Traumatic chemical oral ulceration: a case report and review of the literature  

Microsoft Academic Search

A 34-year-old man experienced extensive oral ulceration as a consequence of attempted ingestion of sulphuric acid as part of an act of deliberate self harm. All oral lesions healed within 28 days after local and systemic therapy. Oral ulceration has many potential causes ranging from physical trauma to malignancy. Chemicals are a less common cause of traumatic ulceration. Most chemical

S. R. Porter; S. Fedele; C. Gilvetti

2010-01-01

131

Lymphatic Invasion Predicts Aggressive Behavior in Melanocytic Tumors of Uncertain Malignant Potential (MELTUMP)  

PubMed Central

BACKGROUND Lymphatic invasion (LI) identified by immunohistochemical staining is common in primary cutaneous melanoma, and LI has been shown to be an independent prognostic factor in melanoma. Its prognostic significance in melanocytic tumors of uncertain malignant potential (MELTUMP) has not been well characterized. METHODS This study included 32 patients with provisional diagnoses of MELTUMP. Lesions were evaluated for tumor thickness, the presence of ulceration, mitotic figures, mitotic figures at the base, tumor infiltrating lymphocytes (TILs), as well as peritumoral and intratumoral lymphatic density. Dual immunohistochemical staining was used to microscopically detect lymphatic endothelium (podoplanin) containing melanoma cells (S-100), with the aid of multispectral imaging in select cases. Univariate analysis was performed to identify associations between clinical and pathologic variables and melanoma related events. RESULTS The 32 patients had a median of 111 months follow-up. Two patients subsequently died of melanoma-related disease, one died of unknown causes, five developed nodal metastases, and the remainder showed no evidence of progressive disease. LI was identified in 8/32 cases (25%) by dual immunohistochemical stains, including both cases in which patients died of melanoma-related disease, one patient with bulky nodal metastasis, one of four patients with microscopic nodal metastases, and in four patients who showed no evidence of progressive disease. The presence of lymphatic invasion was associated with melanoma metastases or melanoma related death (p= 0.05). CONCLUSION The presence of lymphatic invasion by dual immunohistochemistry in MELTUMPs is associated with a poorer prognosis, specifically with melanoma metastasis and may therefore serve as a useful prognostic factor for risk stratifying patients with these diagnostically challenging lesions.

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

2013-01-01

132

Potential Factors for Inadequate Voriconazole Plasma Concentrations in Intensive Care Unit Patients and Patients with Hematological Malignancies  

PubMed Central

Voriconazole plasma concentrations (VPCs) vary widely, and concentrations outside the therapeutic range are associated with either worse outcome in invasive aspergillosis (IA) or increased toxicity. The primary goal of this cohort study conducted in a real-life setting was to identify potential factors associated with inadequate VPCs in ICU patients and patients with hematological malignancies. Within a period of 12 months, trough VPCs were obtained and analyzed with high-performance liquid chromatography, and the adequate range was defined as 1.5 to 5.5 mg/liter. VPCs of <1.5 mg/liter were defined as low, whereas VPCs of >5.5 mg/liter were defined as potentially toxic. A total of 221 trough VPCs were obtained in 61 patients receiving voriconazole, and 124/221 VPCs (56%) were found to be low. Multivariate analysis revealed that low VPCs were significantly associated with clinical failure of voriconazole, prophylactic use, younger age, underlying hematological malignancy, concomitant proton pump inhibitor (PPI) (pantoprazole was used in 88% of the patients), and absence of side effects. Low VPCs remained an independent predictor of clinical failure of voriconazole. The defined adequate range was reached in 79/221 (36%) VPCs. In 18 samples (8%), potentially toxic levels were measured. Multivariate analysis revealed higher body mass index (BMI), absence of hematological malignancy, therapeutic application, and diarrhea as factors associated with potentially toxic VPCs. Neurotoxic adverse events occurred in six patients and were mostly associated with VPCs in the upper quartile of our defined adequate range. In conclusion, potential factors like younger age, prophylaxis, underlying hematological malignancy, BMI, and concomitant PPI should be considered within the algorithm of voriconazole treatment.

Duettmann, Wiebke; Raggam, Reinhard B.; Seeber, Katharina; Troppan, Katharina; Fruhwald, Sonja; Prueller, Florian; Wagner, Jasmin; Valentin, Thomas; Zollner-Schwetz, Ines; Wolfler, Albert

2013-01-01

133

Potential factors for inadequate voriconazole plasma concentrations in intensive care unit patients and patients with hematological malignancies.  

PubMed

Voriconazole plasma concentrations (VPCs) vary widely, and concentrations outside the therapeutic range are associated with either worse outcome in invasive aspergillosis (IA) or increased toxicity. The primary goal of this cohort study conducted in a real-life setting was to identify potential factors associated with inadequate VPCs in ICU patients and patients with hematological malignancies. Within a period of 12 months, trough VPCs were obtained and analyzed with high-performance liquid chromatography, and the adequate range was defined as 1.5 to 5.5 mg/liter. VPCs of <1.5 mg/liter were defined as low, whereas VPCs of >5.5 mg/liter were defined as potentially toxic. A total of 221 trough VPCs were obtained in 61 patients receiving voriconazole, and 124/221 VPCs (56%) were found to be low. Multivariate analysis revealed that low VPCs were significantly associated with clinical failure of voriconazole, prophylactic use, younger age, underlying hematological malignancy, concomitant proton pump inhibitor (PPI) (pantoprazole was used in 88% of the patients), and absence of side effects. Low VPCs remained an independent predictor of clinical failure of voriconazole. The defined adequate range was reached in 79/221 (36%) VPCs. In 18 samples (8%), potentially toxic levels were measured. Multivariate analysis revealed higher body mass index (BMI), absence of hematological malignancy, therapeutic application, and diarrhea as factors associated with potentially toxic VPCs. Neurotoxic adverse events occurred in six patients and were mostly associated with VPCs in the upper quartile of our defined adequate range. In conclusion, potential factors like younger age, prophylaxis, underlying hematological malignancy, BMI, and concomitant PPI should be considered within the algorithm of voriconazole treatment. PMID:23629724

Hoenigl, Martin; Duettmann, Wiebke; Raggam, Reinhard B; Seeber, Katharina; Troppan, Katharina; Fruhwald, Sonja; Prueller, Florian; Wagner, Jasmin; Valentin, Thomas; Zollner-Schwetz, Ines; Wölfler, Albert; Krause, Robert

2013-07-01

134

Phase Ia/II, two-arm, open-label, dose-escalation study of oral panobinostat administered via two dosing schedules in patients with advanced hematologic malignancies.  

PubMed

Panobinostat is a potent oral pandeacetylase inhibitor that leads to acetylation of intracellular proteins, inhibits cellular proliferation and induces apoptosis in leukemic cell lines. A phase Ia/II study was designed to determine the maximum-tolerated dose (MTD) of daily panobinostat, administered on two schedules: three times a week every week or every other week on a 28-day treatment cycle in patients with advanced hematologic malignancies. The criteria for hematologic dose-limiting toxicities differed between patients with indications associated with severe cytopenias at baseline (leukemia and myeloid disorders) and those less commonly associated with baseline cytopenias (lymphoma and myeloma). In patients with leukemia and myeloid disorders, 60?mg was the MTD for weekly as well as biweekly panobinostat. In patients with lymphoma and myeloma, 40?mg was the recommended dose for phase II evaluation (formal MTD not determined) of weekly panobinostat, and 60 mg was the MTD for biweekly panobinostat. Overall, panobinostat-related grade 3-4 adverse events included thrombocytopenia (41.5%), fatigue (21%) and neutropenia (21%). Single-agent activity was observed in several indications, including Hodgkin lymphoma and myelofibrosis. This phase Ia/II study provided a broad analysis of the safety profile and efficacy of single-agent panobinostat in patients with hematologic malignancies. PMID:23385375

DeAngelo, D J; Spencer, A; Bhalla, K N; Prince, H M; Fischer, T; Kindler, T; Giles, F J; Scott, J W; Parker, K; Liu, A; Woo, M; Atadja, P; Mishra, K K; Ottmann, O G

2013-08-01

135

Pyruvate Dehydrogenase Kinase as a Potential Therapeutic Target for Malignant Gliomas  

PubMed Central

Metabolic aberrations in the form of altered flux through key metabolic pathways are the major hallmarks of several life-threatening malignancies including malignant gliomas. These adaptations play an important role in the enhancement of the survival and proliferation of gliomas at the expense of the surrounding normal/healthy tissues. Recent studies in the field of neurooncology have directly targeted the altered metabolic pathways of malignant tumor cells for the development of anti-cancer drugs. Aerobic glycolysis due to elevated production of lactate from pyruvate regardless of oxygen availability is a common metabolic alteration in most malignancies. Aerobic glycolysis offers survival advantages in addition to generating substrates such as fatty acids, amino acids and nucleotides required for the rapid proliferation of cells. This review outlines the role of pyruvate dehydrogenase kinase (PDK) in gliomas as an inhibitor of pyruvate dehydrogenase that catalyzes the oxidative decarboxylation of pyruvate. An in-depth investigation on the key metabolic enzyme PDK may provide a novel therapeutic approach for the treatment of malignant gliomas.

Jha, Mithilesh Kumar

2013-01-01

136

Pyruvate dehydrogenase kinase as a potential therapeutic target for malignant gliomas.  

PubMed

Metabolic aberrations in the form of altered flux through key metabolic pathways are the major hallmarks of several life-threatening malignancies including malignant gliomas. These adaptations play an important role in the enhancement of the survival and proliferation of gliomas at the expense of the surrounding normal/healthy tissues. Recent studies in the field of neurooncology have directly targeted the altered metabolic pathways of malignant tumor cells for the development of anti-cancer drugs. Aerobic glycolysis due to elevated production of lactate from pyruvate regardless of oxygen availability is a common metabolic alteration in most malignancies. Aerobic glycolysis offers survival advantages in addition to generating substrates such as fatty acids, amino acids and nucleotides required for the rapid proliferation of cells. This review outlines the role of pyruvate dehydrogenase kinase (PDK) in gliomas as an inhibitor of pyruvate dehydrogenase that catalyzes the oxidative decarboxylation of pyruvate. An in-depth investigation on the key metabolic enzyme PDK may provide a novel therapeutic approach for the treatment of malignant gliomas. PMID:24904893

Jha, Mithilesh Kumar; Suk, Kyoungho

2013-10-01

137

Ten-Eleven Translocation-2 gene mutations: A potential new molecular marker in malignant gliomas (Review)  

PubMed Central

Alterations of the Ten-Eleven Translocation-2 (TET2) gene in myeloid malignancies and isocitrate dehydrogenase (IDH) gene mutations in gliomas and myeloid malignancies have recently been identified using molecular, comparative genomic hybridization and single nucleotide polymorphism array techniques. The mutations of the TET2 gene have been shown to be mutually exclusive with IDH1/2 mutations in acute myeloid leukemia (AML) and evidence has been found to provide a biochemical basis for the mutual exclusivity of IDH1/2 and TET2 gene mutations. Based on mounting evidence, we aimed to investigate whether TET2 mutations may be identified as novel mutations in malignant gliomas without IDH1/2 mutations, and indicate their possible significance in gliomas.

YU, LEI; QI, SONGTAO

2012-01-01

138

Chitosan microparticles containing plasmid DNA as potential oral gene delivery system  

Microsoft Academic Search

The potential of chitosan as a polycationic gene carrier for oral administration has been explored since 1990s. Chitosan has been shown to effectively bind DNA in saline or acetic acid solution and protect DNA from nuclease degradation. In this study, pDNA (plasmid DNA) was encapsulated in chitosan microparticles. Chitosan–DNA microparticles were prepared using a complex coacervation process and stability of

Ülker Guliyeva; Filiz Öner; ?ule Özsoy; R?fk? Haziro?lu

2006-01-01

139

Vacuum-assisted excision of breast lesions of uncertain malignant potential (B3) – an alternative to surgery in selected cases  

Microsoft Academic Search

To assess whether vacuum-assisted excision (VAE) is a safe alternative to surgery in the treatment of breast lesions of uncertain malignant potential (B3) in which no atypia is present on needle core biopsy (NCB). Forty two VAE procedures were performed for B3 lesions. Twenty four (57%) were papillary lesions. Eighteen (43%) were radial scars. Two patients (4.7%) were upgraded to

S. L. Tennant; A. Evans; L. J. Hamilton; J. James; A. H. S. Lee; Z. Hodi; I. O. Ellis; E. A. Rakha; A. R. M. Wilson

2008-01-01

140

Contribution of Plasminogen Activation towards the Pathogenic Potential of Oral Streptococci  

PubMed Central

Oral streptococci are a heterogeneous group of human commensals, with a potential to cause serious infections. Activation of plasminogen has been shown to increase the virulence of typical human pathogenic streptococci such as S. pneumoniae. One important factor for plasminogen activation is the streptococcal ?-enolase. Here we report that plasminogen activation is also common in oral streptococci species involved in clinical infection and that it depends on the action of human plasminogen activators. The ability to activate plasminogen did not require full conservation of the internal plasminogen binding sequence motif FYDKERKVY of ?-enolase that was previously described as crucial for increased plasminogen binding, activation and virulence. Instead, experiments with recombinant ?-enolase variants indicate that the naturally occurring variations do not impair plasminogen binding. In spite of these variations in the internal plasminogen binding motif oral streptococci showed similar activation of plasminogen. We conclude that the pathomechanism of plasminogen activation is conserved in oral streptococci that cause infections in human. This may contribute to their opportunistic pathogenic character that is unfurled in certain niches.

Itzek, Andreas; Gillen, Christine M.; Fulde, Marcus; Friedrichs, Claudia; Rodloff, Arne C.; Chhatwal, Gursharan S.; Nitsche-Schmitz, Daniel Patric

2010-01-01

141

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

PubMed Central

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 are needed to elucidate the complex interplay between chromatin structure, its modifications and recurrence of PUNLMP.

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

2014-01-01

142

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

PubMed

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. PMID:24486347

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

2014-03-10

143

HMBA induces cell death and potentiates doxorubicin toxicity in malignant mesothelioma cells  

Microsoft Academic Search

Purpose Malignant pleural mesothelioma (MM), a rare tumor characterized by high local invasiveness and low metastatic efficiency, is poorly responsive to current therapeutic approaches. The aim of the present study was to evaluate the cytotoxic efficacy of the hybrid polar compound hexamethylene bisacetamide (HMBA), either as a single agent or in combination with the anthracycline doxorubicin (DOX), against MM cells.

Camilla Palumbo; Loredana Albonici; Roberto Bei; Chiara Bocci; Susanna Scarpa; Paolo Di Nardo; Andrea Modesti

2004-01-01

144

TUMOR SIZE IS ASSOCIATED WITH MALIGNANT POTENTIAL IN RENAL CELL CARCINOMA  

PubMed Central

Objective We evaluated our experience with renal cortical tumors to determine if tumor size is associated with malignant histology and/or nuclear grade. Materials and Methods We identified 2,675 patients treated surgically at Memorial Sloan-Kettering for renal cell carcinoma (RCC) or a benign tumor between 1989 and 2007. Histologic subtype and tumor size were obtained from our kidney cancer database and logistic regression analyses were performed. Results Among the 2,675 tumors, 311 (12%) were benign while 2,364 (88%) were RCC. The odds ratio for association of malignancy with tumor size was 1.16 (95% CI 1.11–1.22; p<0.001), indicating that each 1cm increase in tumor size was associated with a 16% increase in the odds of malignancy. The percentage of benign tumors decreased from 38% for those less than 1 cm to 7% for tumors 7 cm or greater. For patients with clear cell RCC, each 1 cm increase in tumor size increased the odds of a high grade (Fuhrman grade 3–4) compared with a low grade (Fuhrman grade 1–2) tumor by 25% (odds ratio 1.25, 95% CI 1.21–1.30; p<0.001). For this subset, the percentage of high grade tumors increased from 0% for tumors <1cm to 59% for tumors >7cm. Conclusions Our results confirm previous observations suggesting that the risk of malignancy and risk of high grade tumors increases with tumor size. Patients with small renal masses have a low risk for harboring a high-grade clear cell malignancy which may be useful during initial consultation.

Thompson, R. Houston; Kurta, Jordan M; Kaag, Matthew; Tickoo, Satish K.; Kundu, Shilajit; Katz, Darren; Nogueira, Lucas; Reuter, Victor E.; Russo, Paul

2009-01-01

145

Conversion of highly malignant colon cancer from an aggressive to a controlled disease by oral administration of a metalloproteinase inhibitor.  

PubMed

In this study, we describe the activity of CT1746, an orally-active synthetic MMP inhibitor that has a greater specificity for gelatinase A, gelatinase B and stromelysin than for interstitial collagenase and matrilysin, in a nude mouse model that better mimics the clinical development of human colon cancer. The model is constructed by surgical orthotopic implantation (SOI) of histologically-intact tissue of the metastatic human colon tumor cell line Co-3. Animals were gavaged with CT1746 twice a day at 100 mg/kg for 5 days after the SOI of Co-3 for 43 days. In this model CT1746 significantly prolonged the median survival time of the tumor-bearing animals from 51 to 78 days. Significant efficacy of CT1746 was observed on primary tumor growth (32% reduction in mean tumor area at day 36), total spread and metastasis (6/20 treated animals had no detectable spread and metastasis at autopsy compared to 100% incidence of secondaries in control groups). Efficacy of CT1746 could also be seen on reducing tumor spread and metastasis to individual organ sites such as the abdominal wall, cecum and lymph nodes compared to vehicle and untreated controls. We conclude that chronic administration of a peptidomimetic MMP inhibitor via the oral route is feasible and results in inhibition of solid tumor growth, spread and metastasis with increase in survival in this model of human cancer, thus converting aggressive cancer to a more controlled indolent disease. PMID:9062395

An, Z; Wang, X; Willmott, N; Chander, S K; Tickle, S; Docherty, A J; Mountain, A; Millican, A T; Morphy, R; Porter, J R; Epemolu, R O; Kubota, T; Moossa, A R; Hoffman, R M

1997-03-01

146

Oral Cancer Facts  

MedlinePLUS

... in a localized intra oral area. Besides the metastasis, at these later stages, the primary tumor has ... oral cancers. Added to decrease the possibility of metastasis, to sensitize the malignant cells to radiation, to ...

147

Chemopreventive potential of flavonoids in oral squamous cell carcinoma in human studies.  

PubMed

Evidence available from nutritional epidemiology has indicated an inverse association between regular consumption of fruits and vegetables and the risk of developing certain types of cancer. In turn, preclinical studies have attributed the health-promoting effects of plant foods to some groups of phytochemicals, by virtue of their many biological activities. In this survey, we briefly examine the chemopreventive potential of flavonoids and flavonoid-rich foods in human oral carcinogenesis. Despite the paucity of data from clinical trials and epidemiological studies, in comparison to in vitro/in vivo investigations, a high level of evidence has been reported for epigallocatechin gallate (EGCG) and anthocyanins. These flavonoids, abundant in green tea and black raspberries, respectively, represent promising chemopreventive agents in human oral cancer. PMID:23857227

Iriti, Marcello; Varoni, Elena Maria

2013-07-01

148

Chemopreventive Potential of Flavonoids in Oral Squamous Cell Carcinoma in Human Studies  

PubMed Central

Evidence available from nutritional epidemiology has indicated an inverse association between regular consumption of fruits and vegetables and the risk of developing certain types of cancer. In turn, preclinical studies have attributed the health-promoting effects of plant foods to some groups of phytochemicals, by virtue of their many biological activities. In this survey, we briefly examine the chemopreventive potential of flavonoids and flavonoid-rich foods in human oral carcinogenesis. Despite the paucity of data from clinical trials and epidemiological studies, in comparison to in vitro/in vivo investigations, a high level of evidence has been reported for epigallocatechin gallate (EGCG) and anthocyanins. These flavonoids, abundant in green tea and black raspberries, respectively, represent promising chemopreventive agents in human oral cancer.

Iriti, Marcello; Varoni, Elena Maria

2013-01-01

149

CD9 Negatively Regulates CD26 Expression and Inhibits CD26-Mediated Enhancement of Invasive Potential of Malignant Mesothelioma Cells  

PubMed Central

CD26/dipeptidyl peptidase IV is a cell surface glycoprotein which consists of multiple functional domains beside its ectopeptidase site. A growing body of evidence indicates that elevated expression of CD26 correlates with disease aggressiveness and invasive potential of selected malignancies. To further explore the molecular mechanisms involved in this clinical behavior, our current work focused on the interaction between CD26 and CD9, which were recently identified as novel markers for cancer stem cells in malignant mesothelioma. We found that CD26 and CD9 co-modulated and co-precipitated with each other in the malignant mesothelioma cell lines ACC-MESO1 and MSTO-211H. SiRNA study revealed that depletion of CD26 led to increased CD9 expression, while depletion of CD9 resulted in increased CD26 expression. Consistent with these findings was the fact that gene transfer of CD26 into CD26-negative MSTO-211H cells reduced CD9 expression. Cell invasion assay showed that overexpression of CD26 or gene depletion of CD9 led to enhanced invasiveness, while CD26 gene depletion resulted in reduced invasive potential. Furthermore, our work suggested that this enhanced invasiveness may be partly mediated by ?5?1 integrin, since co-precipitation studies demonstrated an association between CD26 and ?5?1 integrin. Finally, gene depletion of CD9 resulted in elevated protein levels and tyrosine phosphorylation of FAK and Cas-L, which are downstream of ?1 integrin, while depletion of CD26 led to a reduction in the levels of these molecules. Collectively, our findings suggest that CD26 potentiates tumor cell invasion through its interaction with ?5?1 integrin, and CD9 negatively regulates tumor cell invasion by reducing the level of CD26-?5?1 integrin complex through an inverse correlation between CD9 and CD26 expression. Our results also suggest that CD26 and CD9 serve as potential biomarkers as well as promising molecular targets for novel therapeutic approaches in malignant mesothelioma and other malignancies.

Okamoto, Toshihiro; Iwata, Satoshi; Yamazaki, Hiroto; Hatano, Ryo; Komiya, Eriko; Dang, Nam H.; Ohnuma, Kei; Morimoto, Chikao

2014-01-01

150

Epigenetic Disregulation in Oral Cancer  

PubMed Central

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

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

2012-01-01

151

A phase I clinical and pharmacokinetic study of CS-682 administered orally in advanced malignant solid tumors.  

PubMed

CS-682 (1-(2-C-cyano-2-deoxy-beta-D-arabino-pentofuranosyl)-N4-palmitoylcytosine) is a novel orally administered 2'-deoxycytidine-type antimetabolite, which has a wide spectrum of antitumor activity in human tumor xenograft models. We conducted a phase I study to define the toxicity, pharmacokinetics and antitumor activity of CS-682 in patients with advanced solid tumors. Forty patients were enrolled to receive escalating doses of CS-682. CS-682 was given orally, once daily three times a week (Monday, Wednesday and Friday), for four weeks consecutively, followed by a two-week rest period. Twenty-two men and 18 women, median age 63.5 (range 31 to 82) were treated. The most common tumor type was colorectal cancer with 15 patients. Others tumors occurring in 3 or more patients included prostate, breast and lung carcinomas. Sixty percent of the patients had received greater than 2 prior chemotherapy programs. Patients have been treated at each of the following dose levels (mg/m2/day): 1.5, 12, 20, 25, 30, 50, 67, 90, 120, 160 and 220. Non hematologic toxicities grade 3 [NCI Common Toxicity Criteria (version 2.0)] related to treatment included nausea in 2, vomiting in 1, anorexia and asthenia in 2, and dehydration in 1. Severe hematologic toxicities (grade 3-4) were seen more frequently with 10 patients experiencing grade 3-4 neutropenia, 2 with grade 4 thrombocytopenia and 2 with grade 3 anemia. Neutropenia requiring hospitalization occurred in 3 patients. Dose-limiting neutropenia was observed at 220 mg/m2/day. The maximum tolerated dose was determined to be 160 mg/m2/day. No tumor responses were observed in this study. Six patients experienced stable disease, including one who has stable disease after having received 34 courses of CS-682. After oral administration, CS-682 is rapidly absorbed and metabolized to CNDAC, which is further metabolized by cytidine deaminase to the inactive product CNDAU. Peak plasma concentrations of CNDAC were achieved 2.2 +/- 0.9 h after drug administration and the terminal elimination half-life was 1.7 +/- 1.5 h. Measurable concentrations of CNDAU were first seen 0.60 +/- 0.31 h, peak plasma concentrations were achieved 3.1 +/- 0.9 h after the CS-682 dose, and the terminal elimination half-life was 2.3 +/- 1.7 h. The recommended phase 2 starting dose for the 3 days/week regimen of CS-682 is 160 mg/m2/day for 4 weeks repeated after a 2-week rest period. PMID:16502355

Delaunoit, Thierry; Burch, Patrick A; Reid, Joel M; Camoriano, John K; Kobayash, Tomowo; Braich, Theodore A; Kaur, Judith S; Rubin, Joseph; Erlichman, Charles

2006-07-01

152

Pulmonary Metastases of a Uterine Smooth Muscle Tumour with Undefined Malignancy Potential  

PubMed Central

Smooth muscle neoplasms with atypical proliferative behaviour, but without clear histopathological malignancy represent a diagnostic and therapeutic challenge, as distinction from a sarcoma can be difficult and no guaranteed treatment recommendations are available due to the rarity of these changes. In the event of uncertain primary histology, even metastases cannot be assessed as malignancy criteria, but may contribute to the clarification of the histology. Similarities with other smooth muscle proliferations, such as lymphangioleiomyomatosis, are striking. The diagnostic difficulties and treatment options are explained based on the example of a 59-year-old patient, in whom a retroperitoneal mass and pulmonary lesion of such a tumour occurred 4 years after a hysterectomy. Even though the genesis and histological diagnostics have not been conclusively clarified, slow growth and a low recurrence rate for post-menopausal patients allow for a wait-and-see approach, whereby the option for anti-hormonal treatment exists in the event of positive evidence of hormone receptors.

Esch, M.; Teschner, M.; Braesen, J.-H.

2014-01-01

153

Potential diagnostic, prognostic and therapeutic implications of some new regulatory proteins in hematologic malignancies.  

PubMed

Multiple cell surface receptors play an important role in the biology of hematological malignant cells. Like already clustered monoclonal antibodies, the use of new markers of differentiation provide some new information about their structure and function. Here we consider the role of few selected regulatory proteins that are most frequently involved in the processes of activation, cell differentiation and proliferation of human hematological malignant cells. These molecules, being either lineage-restricted or multi-lineage cell activation ones, are involved in cell-cell and cell-matrix communications. They are involved in various leukocyte functions such as mobility, interaction with endothelium, and homing. Since physiologic cell growth involves not only cell division, but also programmed-cell death, we considered some apoptosis-regulatory molecules implicated in the clinical heterogeneity of hematological malignancies. The presence or absence of staining for these molecules is not only an important discriminatory immunophenotypic feature, but it appears useful also for prognosis and particularly in an experimental therapeutical setting. The prognostic significance of cell-expression of these molecules has not yet been clearly established, but it might be helpful in the evaluation of stability and progression of the disease. PMID:10965815

Milosevi?, D

2000-06-01

154

Ranpirnase as a potential antitumor ribonuclease treatment for mesothelioma and other malignancies.  

PubMed

Ranpirnase, originally isolated from oocytes of the northern leopard frog (Rana pipiens), is a member of the pancreatic RNase A superfamily of ribonucleases. Ranpirnase exerts antiproliferative and cytotoxic effects in vitro and in vivo and has been shown to act synergistically with different cancer therapeutic agents. The cytotoxic and cytostatic effects of ranpirnase are the consequence of tRNA degradation that results in the disruption of protein translation and the induction of programmed cell death (apoptosis). Ranpirnase has been shown to target malignant cells both in human cancer cell lines and in animal models, and has demonstrated efficacy in the treatment of several human cancers in clinical studies. Most clinical studies have been conducted in patients with malignant mesothelioma, and a confirmatory Phase IIIb trial is currently underway for the treatment of this disease. Owing to its selective destruction of malignant cells and favorable toxicology profile, ranpirnase is a promising antitumor agent with ideal attributes that are generally lacking in conventional cytotoxic drugs. PMID:18518759

Beck, Amanda K; Pass, Harvey I; Carbone, Michele; Yang, Haining

2008-06-01

155

Identification of genes potentially involved in the increased risk of malignancy in NF1-microdeleted patients.  

PubMed

Patients with NF1 microdeletion develop more neurofibromas at a younger age, and have an increased risk of malignant peripheral nerve sheath tumors (MPNSTs). We postulated that the increased risk of malignancy could be due to inactivation, in addition to NF1, of a second tumor suppressor gene located in the typical 1.4-Mb microdeletion found in most of the microdeleted patients. We investigated the expression of NF1, the other 16 protein-coding genes and the 2 microRNAs located in the 1.4-Mb microdeletion by means of real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) in a large series of human dermal and plexiform neurofibromas and MPNSTs. Five genes were significantly upregulated: OMG and SUZ12 in plexiform neurofibromas and ATAD5, EVI2A and C17orf79 in MPNSTs. More interestingly, two genes were significantly downregulated (RNF135 and CENTA2) in tumor Schwann cells from MPNST biopsies and in MPNST cell lines. This study points to the involvement of several genes (particularly RNF135 and CENTA2) in the increased risk of malignancy observed in NF1-microdeleted patients. PMID:20844836

Pasmant, Eric; Masliah-Planchon, Julien; Lévy, Pascale; Laurendeau, Ingrid; Ortonne, Nicolas; Parfait, Béatrice; Valeyrie-Allanore, Laurence; Leroy, Karen; Wolkenstein, Pierre; Vidaud, Michel; Vidaud, Dominique; Bičche, Ivan

2011-01-01

156

Identification of Genes Potentially Involved in the Increased Risk of Malignancy in NF1-Microdeleted Patients  

PubMed Central

Patients with NF1 microdeletion develop more neurofibromas at a younger age, and have an increased risk of malignant peripheral nerve sheath tumors (MPNSTs). We postulated that the increased risk of malignancy could be due to inactivation, in addition to NF1, of a second tumor suppressor gene located in the typical 1.4-Mb microdeletion found in most of the microdeleted patients. We investigated the expression of NF1, the other 16 protein-coding genes and the 2 microRNAs located in the 1.4-Mb microdeletion by means of real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) in a large series of human dermal and plexiform neurofibromas and MPNSTs. Five genes were significantly upregulated: OMG and SUZ12 in plexiform neurofibromas and ATAD5, EVI2A and C17orf79 in MPNSTs. More interestingly, two genes were significantly downregulated (RNF135 and CENTA2) in tumor Schwann cells from MPNST biopsies and in MPNST cell lines. This study points to the involvement of several genes (particularly RNF135 and CENTA2) in the increased risk of malignancy observed in NF1-microdeleted patients.

Pasmant, Eric; Masliah-Planchon, Julien; Levy, Pascale; Laurendeau, Ingrid; Ortonne, Nicolas; Parfait, Beatrice; Valeyrie-Allanore, Laurence; Leroy, Karen; Wolkenstein, Pierre; Vidaud, Michel; Vidaud, Dominique; Bieche, Ivan

2011-01-01

157

Preparation and characterization of tetrandrine-phospholipid complex loaded lipid nanocapsules as potential oral carriers  

PubMed Central

Background Tetrandrine is an active constituent that is extracted from the root tuber of the Chinese herb Stephania tetrandra S. Moore. It has shown various pharmacological effects, such as antitumor activity, multidrug resistance reversal, and hepatic fibrosis resistance. In clinical applications, it has been used to treat hypertension, pneumosilicosis, and lung cancer. However, the poor water solubility of tetrandrine has limited its application. In this study, a newly emerging oral drug carrier of phospholipid complex loaded lipid nanocapsules was developed to improve the oral bioavailability of tetrandrine. Methods The phospholipid complex was prepared with the solvent-evaporation method to enhance the liposolubility of tetrandrine. The formation of the phospholipid complex was confirmed with a solubility study, infrared spectroscopy, and a differential scanning calorimetry (DSC) analysis. The tetrandrine-phospholipid complex loaded lipid nanocapsules (TPC-LNCs) were prepared using the phase inversion method. Lyophilization was performed with mannitol (10%) as a cryoprotectant. TPC-LNCs were characterized according to their particle size, zeta potential, encapsulation efficiency, morphology by transmission electron microscopy, and crystallinity by DSC. In addition, the in vitro release of tetrandrine from TPC-LNCs was examined to potentially illustrate the in vivo release behavior. The in vivo bioavailability of TPC-LNCs was studied and compared to tetrandrine tablets in rats. Results The liposolubility of tetrandrine in n-octanol improved from 8.34 ?g/mL to 35.64 ?g/mL in the tetrandrine-phospholipid complex. The prepared TPC-LNCs were spherical-shaped particles with a small size of 40 nm and a high encapsulation efficiency of 93.9%. DSC measurements revealed that the crystalline state was less ordered in lipid nanocapsules. The in vitro release study demonstrated a fast release of approximately 25% in the first 1 hour, which was followed by a sustained release of 70% over 12 hours. The relative bioavailability of TPC-LNCs compared to that of tablets was 208%, indicating a significant improvement in the oral absorption of tetrandrine. Conclusion The TPC-LNCs system developed in this study is a promising carrier that improves the oral bioavailability of tetrandrine in rats. The phospholipid complex loaded lipid nanocapsules have great potential for use as an oral drug delivery system for moderately lipophilic drugs that are encapsulated in the lipid nanocapsules.

Zhao, Yi-qing; Wang, Li-ping; Ma, Chao; Zhao, Kun; Liu, Ying; Feng, Nian-ping

2013-01-01

158

Carcinogenic Potential of Rotenone: Subchronic Oral and Peritoneal Administration to Rats and Chronic Dietary Administration to Syrian Golden Hamsters.  

National Technical Information Service (NTIS)

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

R. I. Freudenthal A. P. Leber D. C. Thake R. L. Baron

1981-01-01

159

Oral cancer in the UAE: a multicenter, retrospective study  

PubMed Central

Aim To determine the prevalence of various malignant oral lesions in the UAE and correlate cases of squamous cell carcinomas with age, gender, site, grade, clinical presentations at the time of diagnosis, and the prevalence of neck metastasis. Materials and methods A multicenter, retrospective study was conducted at four major hospitals in the UAE. The study was based on histopathology reports of biopsies of oral tissues. Results Of the 992 oral biopsy reports retrieved, 147 cases of malignant tumors were found which accounted for 14.9% of the total biopsies. Fifteen different types of malignant lesions were diagnosed, of which oral squamous cell carcinoma (OSCC) was the most prevalent and made up 11.4% of the overall oral biopsies retrieved. The commonest presentation of cancer was ulceration (31.17%), followed by lumps and white lesions. The most common site where the lesions were diagnosed was the tongue (51.9%), followed by the cheeks and lips. OSCC accounted for 77% of all malignancies reported. Neck dissections were conducted in only 20.8% of all OSCC cases diagnosed at Mafraq and Tawam hospitals, of which 43.75% showed evidence of neck metastasis. Conclusion Oral cancer is not an uncommon disease in the UAE. This may mandate more awareness campaigning, including screening procedures for early detection of cancerous lesions and other potentially malignant oral diseases. Elective neck dissections to detect lymph node metastasis should be more routinely performed, in particular for tongue carcinomas because of the early neck involvement potential.

Anis, Raeefa; Gaballah, Kamis

2013-01-01

160

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

PubMed Central

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 delivery applications.

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

2011-01-01

161

Clinical applications of palifermin: amelioration of oral mucositis and other potential indications.  

PubMed

Mucositis is one of the most significant toxicities in cancer patients undergoing cytotoxic treatment. It can have a negative impact on both quality of life and health economics. Severe oral mucositis can contribute to hospitalization, need for narcotic analgesics, total parentral nutrition, suboptimal delivery of anti-neoplastic treatment, and morbidity and mortality. Palifermin, a recombinant derivative of human keratinocyte growth factor, is the first active agent approved by the FDA for the prevention of severe oral mucositis in patients undergoing haematopoietic stem cell transplantation (HSCT). Several studies have also shown significant reduction in the incidence, severity and/or duration of oral mucositis in other high-risk settings such as concurrent chemoradiotherapy (CT/RT) for patients with head and neck cancer, and use of mucotoxic chemotherapeutic agents such as doxorubicin in sarcoma and fluorouracil for the treatment of colorectal cancer. The reduction in mucositis has translated into amelioration of symptoms and improvement in daily functioning as measured by patient-reported outcome in multiple studies. The clinical response to palifermin appears to be related in part to epithelial proliferation and mucosal thickening. Palifermin also has other potential clinical applications including the acceleration of immune reconstitution and inhibition of graft-versus-host disease in patients undergoing HSCT, and mitigation of dysphagia in lung cancer patients treated with concurrent CT/RT. Palifermin is generally well tolerated with mild-to-moderate skin and oral adverse events. Future studies may expand the use of palifermin into other areas that would benefit from its cytoprotective and regenerative effects. PMID:24251854

Vadhan-Raj, Saroj; Goldberg, Jenna D; Perales, Miguel-Angel; Berger, Dietmar P; van den Brink, Marcel R M

2013-11-01

162

Screen-detected breast lesions with malignant needle core biopsy diagnoses and no malignancy identified in subsequent surgical excision specimens (potential false-positive diagnosis)  

Microsoft Academic Search

Although breast needle core biopsy (NCB) is now a standard diagnostic procedure in the triple assessment of screen-detected breast lesions, data on the false-positive diagnoses of malignancy (malignant NCB ‘B5’ with normal\\/benign surgery) are lacking. In this study, we have studied a large series of NCBs (101,440) to assess the causes and pitfalls resulting in false-positive NCB diagnoses and to

Emad A. Rakha; Maysa E. El-Sayed; Jacquie Reed; Andrew H. S. Lee; Andrew J. Evans; Ian O. Ellis

2009-01-01

163

Oncolytic viral therapy and immunotherapy of malignant brain tumors: two potential new approaches of translational research.  

PubMed

Brain tumors arise at a rate of nearly 5/100,000 in the general population, with over 17,000 U.S. residents being diagnosed each year. Approximately 60% of all brain tumors are gliomas, which are derived from interstitial tissue of the brain, such as astrocytic or ependymal tissue, or oligodendrocytes. The traditional protocols for treatment of malignant gliomas include diagnostic surgery, followed by regimens of radio- and chemotherapies. In the case of chemotherapy, the treatment protocols have remained nearly unchanged for over 30 years despite high mortality rates, and with little to no improvement in outcome. New advances in the fields of molecular biology and immunology have resulted in new possibilities for treating malignant gliomas by targeting cellular and molecular mechanisms of tumor cells, and stand in contrast to traditional forms of treatment. In the field of gene therapy, the possibility of using oncolytic viruses, such as HSV-1, for glioma therapy--specifically, of high grade astrocytomas--is being explored, and trials have begun using a replication-selective mutant strain known as G207. An increased understanding of the role of the cytokine TGF-beta2 has led to developments of anti-sense immunotherapy targeting this factor. The two examples mentioned here are discussed in this review and cited as possible improvements in the treatment of high grade astrocytomas. PMID:15000342

Lou, Emil

2004-01-01

164

Expression of neutrophil gelatinase-associated lipocalin in colorectal neoplastic progression: a marker of malignant potential?  

PubMed Central

Background: Neutrophil gelatinase-associated lipocalin (NGAL) has a diverse functional repertoire, involved in the innate immune response as well as cell growth and differentiation. Expression has been linked to malignant disease development and progression. Methods: Neutrophil gelatinase-associated lipocalin expression was assessed immunohistochemically in 98 colorectal neoplastic lesions (52 cancer polyps (CaPs) and 46 sporadic adenoma/adjacent normal mucosa paired specimens) to investigate association with adenoma progression and early colorectal carcinogenesis. Results: Within CaPs, all adenomatous and carcinomatous epithelium expressed NGAL, with 92% (43 out of 47) and 58% (19 out of 33) epithelial positivity, respectively, as well as positive stromal cell expression. This was significantly increased compared with normal mucosal epithelium (P=0.0001). Neutrophil gelatinase-associated lipocalin positivity was also identified in sporadic low-grade adenomas, in both the epithelial and stromal compartments as compared with adjacent normal mucosa (P=0.0001 and 0.0002), and this increased along with adenoma size >1?cm (P=0.03). Conclusion: Neutrophil gelatinase-associated lipocalin is expressed by the majority of human neoplastic colorectal lesions. This phenotypic switch occurs at an early stage in neoplastic progression with clear differential expression between normal mucosa and adenomatous polyps, rather than further downstream in disease progression at the adenoma–carcinoma transformation. Thus, NGAL expression is not a useful biomarker for determining disease progression from adenomatous to malignant colorectal neoplasia.

McLean, M H; Thomson, A J; Murray, G I; Fyfe, N; Hold, G L; El-Omar, E M

2013-01-01

165

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

PubMed Central

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

ZHANG, HAOFENG; ZHANG, JUN; WANG, ZHAOQING; LU, DI; FENG, JING; YANG, DONGLING; CHEN, XIUQIN; YAN, XIYUN

2013-01-01

166

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

PubMed Central

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

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

2011-01-01

167

Potential Oral Delivery of 7-Ethyl-10-Hydroxy-Camptothecin (SN-38) using Poly (amidoamine) Dendrimers  

PubMed Central

Purpose To investigate potential application of poly(amidoamine) (PAMAM) dendrimers for improving the delivery of SN-38. Methods Complexes of SN-38 with generation 4 amine terminated PAMAM dendrimers were synthesized with varying amounts of drug. Stability of the complexes as well as influence of complexation on permeability across and cellular uptake by Caco-2 cells was evaluated. Results The complexes were stable at pH 7.4 and drug was released at pH 5. A tenfold increase in permeability and more than hundredfold increase in cellular uptake of the complexes with respect to free SN-38 was observed. Conclusions Studies suggest that complexation with PAMAM dendrimers has the potential to improve the oral bioavailability of SN-38.

Kolhatkar, Rohit B.; Swaan, Peter; Ghandehari, Hamidreza

2009-01-01

168

Prostaglandin D2 formation by malignant melanoma cells correlates inversely with cellular metastatic potential.  

PubMed Central

B16 malignant melanoma cell lines transform arachidonic acid and its transient metabolite, prostaglandin endoperoxide H2, into prostaglandin D2. The highly metastatic line, B16 F10, forms less prostaglandin D2 compared to the moderately metastatic parent line, B16 F1. Since platelet aggregation may be one factor involved in B16 metastasis and since prostaglandin D2 inhibits platelet aggregation, this prostaglandin could affect the outcome of platelet-tumour interactions, which may contribute ultimately to metastasis. Arachidonic acid metabolism may be another one of the intrinsic biochemical properties of tumor cells that affects their metastasis. Our results suggest that quantitative release of unusual prostaglandins must be considered in this context.

Fitzpatrick, F A; Stringfellow, D A

1979-01-01

169

Papillary urothelial neoplasm of low malignant potential of the urinary bladder: clinicopathologic and outcome analysis from a single academic center.  

PubMed

Few long-term single-center studies have addressed the outcome of patients with papillary urothelial neoplasms of low malignant potential. Our study evaluates the behavior of these tumors occurring as primary urinary bladder lesions. For this purpose, 34 primary in-house cases diagnosed and treated between 1998 and 2008 were identified from our medical records. Upon review, 3 cases were upgraded to noninvasive low-grade urothelial carcinomas and excluded from further evaluation. During follow-up (range, 3-108 months; mean, 42 months), 13 patients developed recurrences; and 9 patients progressed to a noninvasive higher grade lesion (8 to low-grade and 1 to high-grade urothelial carcinomas). None of our patients developed stage progression (>pTa) or died of bladder cancer. Size of the primary tumor was associated with the risk of recurrence (P = .043), whereas the number of episodes of recurrence was associated with the likelihood of grade progression (P = .034). In conclusion, recurrences were observed in 42% of all our patients, with a grade progression rate of 29%. None of our patients developed invasive carcinoma or died as a consequence of their disease. Considering the low but definitive risk of recurrence and grade progression, appropriate clinical follow-up of patients with primary papillary urothelial neoplasm of low malignant potential is warranted. PMID:21777949

Lee, Thomas K; Chaux, Alcides; Karram, Sarah; Miyamoto, Hiroshi; Miller, Jeremy S; Fajardo, Daniel A; Epstein, Jonathan I; Netto, George J

2011-11-01

170

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

PubMed Central

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

Hannah, Jeffrey; Zhou, Peng-Bo

2013-01-01

171

Screening of a heptamer-type sgRNA library for potential therapeutic agents against hematological malignancies.  

PubMed

tRNase-Z(L)-utilizing efficacious (TRUE) gene silencing is an RNA-mediated gene expression control technology that has therapeutic potential. This technology is based on the property of tRNase Z(L) that it can cleave any target RNA at any desired site under the direction of an appropriate artificial small guide RNA (sgRNA). To search for novel potential therapeutic sgRNAs for hematological malignancies, we screened a library composed of 156 sgRNAs, and found that 20 sgRNAs can efficiently induce apoptosis in leukemia and/or myeloma cells. Furthermore, we demonstrated that 4 of the 20 sgRNAs can reduce growth rates of HL60 cells in mouse xenograft models. PMID:24768135

Takahashi, Masayuki; Elbarbary, Reyad A; Watanabe, Norihiro; Goto, Atsushi; Kamiya, Daichi; Watabe, Yoshihiro; Uchiyama, Takayoshi; Narita, Miwako; Takahashi, Masuhiro; Takahashi, Yoshiaki; Ishihara, Noriko; Miyazawa, Tatsuya; Yoshida, Tetsuo; Kawano, Mitsuoki; Tamura, Masato; Nashimoto, Masayuki

2014-07-01

172

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

PubMed

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

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

2009-03-01

173

Teriflunomide, an inhibitor of dihydroorotate dehydrogenase for the potential oral treatment of multiple sclerosis.  

PubMed

Teriflunomide, being developed as a potential oral treatment for multiple sclerosis (MS) by sanofi-aventis, is the active metabolite of the rheumatoid arthritis drug leflunomide. Both teriflunomide and leflunomide are inhibitors of the mitochondrial enzyme dihydroorotate dehydrogenase, which is critically involved in pyrimidine synthesis. The production of activated T-cells largely depends on de novo pyrimidine synthesis, and thus pyrimidine depletion is thought to result in the inhibition of immune cell proliferation. Therapeutic efficacy of teriflunomide has been demonstrated in vivo in an experimental autoimmune encephalomyelitis model of MS using Dark Agouti rats. In a phase II, randomized, double-blind, placebo-controlled clinical trial of patients with relapsing-remitting MS, treatment with teriflunomide reduced the number of active lesions in the brain and preliminary evidence indicated a slowing in the development of disability. Recently reported data from the phase III TEMSO clinical trial support these initial findings. Compared with current therapies, teriflunomide has the advantage of oral administration. Thus, if good efficacy is demonstrated, teriflunomide may have a role to play in the future treatment of MS. PMID:21157651

Palmer, Alan M

2010-11-01

174

Differences in Allergenic Potential of Food Extracts following Oral Exposure in Mice Reflect Differences in Digestibility: Potential Approaches to Safety Assessment  

Microsoft Academic Search

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

Christal C. Bowman; MaryJane K. Selgrade

2008-01-01

175

Aurora kinase inhibitors: Potential molecular-targeted drugs for gynecologic malignant tumors  

PubMed Central

Chemotherapy and surgery are important treatment strategies for gynecologic malignant tumors such as ovarian, cervical and endometrial cancer. However, many anticancer drugs currently available are cytotoxic and cause strong adverse reactions in patients. Aurora kinases have attracted increasing attention in recent years as serine/threonine kinases with various roles in cell division, including chromosomal agglutination and segregation, functions of centromeres, centrosomal maturation, spindle formation and cytokinesis. Aurora kinases are overexpressed in a number of cancers and recent studies have shown that they are involved in onco genesis and cause an aberrant increase in centrosome number, emergence of polykaryocytes and failure of cancer inhibition mechanisms. Thus, drugs that inhibit Aurora kinases are likely to exert anticancer effects in various fields, including the gynecologic field. Aurora kinase inhibitors exert antitumor effects in monotherapy and synergistic effects in combination therapy with taxane-based anticancer agents for gynecologic tumors and are likely to increase the efficacy of existing anticancer drugs. Current Aurora kinase inhibitors include ZM447439, Hesperadin, VX-680/MK-0457, AT9283 and Barasertib, and clinical trials are ongoing to verify the effects of these inhibitors.

UMENE, KIYOKO; BANNO, KOUJI; KISU, IORI; YANOKURA, MEGUMI; NOGAMI, YUYA; TSUJI, KOSUKE; MASUDA, KENTA; UEKI, ARISA; KOBAYASHI, YUSUKE; YAMAGAMI, WATARU; NOMURA, HIROYUKI; TOMINAGA, EIICHIRO; SUSUMU, NOBUYUKI; AOKI, DAISUKE

2013-01-01

176

Role of proteomics to differentiate between benign and potentially malignant pancreatic cysts.  

PubMed

Pancreatic cystic neoplasms represent 10-15% of primary cystic masses of the pancreas. While pancreatic cysts are detected with an increasing frequency due to the use of advanced imaging modalities in clinical practice, the diagnosis of pancreatic cystic neoplasms remains unsatisfactory because available diagnostic techniques proved not sensitive enough so far. This study was designed to characterize the proteomic pattern of pancreatic cyst fluids obtained from various cystic lesions. Cyst fluids were collected by direct puncture during open surgery to avoid any possible contamination from other tissues. CEA, CA-19-9, and amylase concentrations were measured using specific immunoassays. After immunodepletion and fractionation by SDS-PAGE, proteins were digested and analyzed by LC-MS/MS. Specific histological lesions were found to be associated with distinct protein patterns. Interestingly, some of these proteins have been proposed as biomarkers of pancreatic cancer. Immunoblots allowed for verifying the differential expression in specific cyst fluids of two selected proteins, olfactomedin-4 and mucin-18. Finally, immunohistochemistry was performed to correlate these data with the expression pattern of olfactomedin-4 and mucin-18 in pancreatic cyst tissues. Results from this study indicate that proteomic analysis of cyst fluid could provide reliable candidates for developing new biomarkers for the preoperative management of malignant and premalignant pancreatic cysts. PMID:21425880

Cuoghi, Aurora; Farina, Annarita; Z'graggen, Kaspar; Dumonceau, Jean-Marc; Tomasi, Aldo; Hochstrasser, Denis F; Genevay, Muriel; Lescuyer, Pierre; Frossard, Jean-Louis

2011-05-01

177

Depleted Uranium. Is it potentially involved in the recent upsurge of malignancies in populations exposed to war dust?  

PubMed

Due to its extreme density, depleted Uranium (DU) has recently entered the warfare industry and became a major pollutant to the biosphere. Although DU is less radioactive than natural Uranium, it still retains all its chemical toxicity. Limited data exists regarding the long-term hazards of DU on humans, however, it is suspected to be a major toxic and mutagenic agent. Literature review reveals the scarcity of the World Health Organization's knowledge regarding related DU-malignancies. Battlefield reports documented a steady rise of malignancies and newborn malformations after war, that is, leukemia in the Balkans, and congenital anomalies and Kaposi sarcoma (KS) in Iraq. Kaposi sarcoma in Iraq has a quite aggressive behavior compared with the classic KS before, suggesting a potential relation with DU, and possibly a different DU related KS-type. Children are more susceptible to radiation than adults. This enlarges the responsibility of the medical communities for an evidence-based attitude towards DU, and to ban its use until proven otherwise. We, as medical bodies have a human approach - stand with man not to be mistreated, and with green norms, which veto all suspected pollutants of the planet. Until further notice, DU should be thoroughly checked for safety, before it kills. PMID:22588807

Shelleh, Hamdi H

2012-05-01

178

Human Papillomavirus in the Lesions of the Oral Mucosa According to Topography  

PubMed Central

Background The association between human papillomavirus (HPV) types and oral lesions has been shown in many studies. Considering the significance that HPV has in the development of malignant and potentially malignant disorders of the oral mucosa, the purpose of this study was to investigate the prevalence of HPV DNA in different oral lesions. In addition, we wanted to elucidate whether the HPV infection is associated predominantly with either the lesion or a particular anatomic site of the oral cavity. Methodology/Principal Findings The study included 246 subjects with different oral lesions, and 73 subjects with apparently healthy oral mucosa (controls). The oral lesions were classified according to their surface morphology and clinical diagnosis. The epithelial cells were collected with a cytobrush from different topographic sites in the oral cavity of the oral lesions and controls. The presence of HPV DNA was evaluated by consensus and type-specific primer-directed polymerase chain reaction. The HPV positivity was detected in 17.7% of oral lesions, significantly more than in apparently healthy mucosa (6.8%), with a higher presence in benign proliferative mucosal lesions (18.6%). High-risk HPV types were predominantly found in potentially malignant oral disorders (HPV16 in 4.3% and HPV31 in 3.4%), while benign proliferative lesions as well as healthy oral mucosa contained mainly undetermined HPV type (13.6 and 6.8%, respectively). Conclusions/Significance The distribution of positive HPV findings on the oral mucosa seems to be more associated with a particular anatomical site than the diagnosis itself. Samples taken from the vermilion border, labial commissures, and hard palate were most often HPV positive. Thus, topography plays a role in HPV prevalence findings in oral lesions. Because of the higher prevalence of the high-risk HPV types in potentially malignant oral disorders, these lesions need to be continuously controlled and treated.

Mravak-Stipetic, Marinka; Sabol, Ivan; Kranjcic, Josip; Knezevic, Marjana; Grce, Magdalena

2013-01-01

179

Oral Tumours  

PubMed Central

The authors of this article review briefly the anatomy of the oral soft tissues and describe the more common benign and malignant tumours of the mouth, giving emphasis to their clinical features. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8

Lecavalier, D.R.; Main, J.H.P.

1988-01-01

180

Itraconazole Oral Solution for Primary Prophylaxis of Fungal Infections in Patients with Hematological Malignancy and Profound Neutropenia: a Randomized, Double-Blind, Double-Placebo, Multicenter Trial Comparing Itraconazole and Amphotericin B  

PubMed Central

Systemic and superficial fungal infections are a major problem among immunocompromised patients with hematological malignancy. A double-blind, double-placebo, randomized, multicenter trial was performed to compare the efficacy and safety of itraconazole oral solution (2.5 mg/kg of body weight twice a day) with amphotericin B capsules (500 mg orally four times a day) for prophylaxis of systemic and superficial fungal infection. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (>0.5 × 109 neutrophils/liter) or up to a maximum of 3 days following the end of neutropenia, unless a systemic fungal infection was documented or suspected. The maximum treatment duration was 56 days. In the intent-to-treat population, invasive aspergillosis was noted in 5 (1.8%) of the 281 patients assigned to itraconazole oral solution and in 9 (3.3%) of the 276 patients assigned to oral amphotericin B; of these, 1 and 4 patients died, respectively. Proven systemic fungal infection (including invasive aspergillosis) occurred in 8 patients (2.8%) who received itraconazole, compared with 13 (4.7%) who received oral amphotericin B. Itraconazole significantly reduced the incidence of superficial fungal infections as compared to oral amphotericin B (2 [1%] versus 13 [5%]; P = 0.004). Although the incidences of suspected fungal infection (including fever of unknown origin) were not different between the groups, fewer patients were administered intravenous systemic antifungals (mainly intravenous amphotericin B) in the group receiving itraconazole than in the group receiving oral amphotericin B (114 [41%] versus 132 [48%]; P = 0.066). Adequate plasma itraconazole levels were achieved in about 80% of the patients from 1 week after the start of treatment. In both groups, the trial medication was safe and well tolerated. Prophylactic administration of itraconazole oral solution significantly reduces superficial fungal infection in patients with hematological malignancies and neutropenia. The incidence of proven systemic fungal infections, the number of deaths due to deep fungal infections, and the use of systemic antifungals tended to be lower in the itraconazole-treated group than in the amphotericin B-treated group, without statistical significance. Itraconazole oral solution is a broad-spectrum systemic antifungal agent with prophylactic activity in neutropenic patients, especially for those at high risk of prolonged neutropenia.

Harousseau, J. L.; Dekker, A. W.; Stamatoullas-Bastard, A.; Fassas, A.; Linkesch, W.; Gouveia, J.; De Bock, R.; Rovira, M.; Seifert, W. F.; Joosen, H.; Peeters, M.; De Beule, K.

2000-01-01

181

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

PubMed

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. PMID:18033772

Bowman, Christal C; Selgrade, Maryjane K

2008-03-01

182

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

PubMed

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

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

2013-06-18

183

Expression of ?-catenin in rat oral epithelial dysplasia induced by 4-nitroquinoline 1-oxide  

Microsoft Academic Search

The aim of this study was to evaluate whether ?-catenin accumulation is useful for diagnosing the malignant potential of oral precancerous lesions. We investigated oral epithelial dysplasia adjacent to early cancer induced by 4-nitroquinoline 1-oxide in rats. Localization of ?-catenin and cell proliferation were detected immunohistochemically, and exon 3 of the ?-catenin gene was analyzed. Accumulation of ?-catenin in the

Kazumichi Sato; Yuichiro Okazaki; Morio Tonogi; Yoichi Tanaka; Gen-yuki Yamane

2002-01-01

184

High Expression of Wee1 Is Associated with Poor Disease-Free Survival in Malignant Melanoma: Potential for Targeted Therapy  

PubMed Central

Notoriously resistant malignant melanoma is one of the most increasing forms of cancer worldwide; there is thus a precarious need for new treatment options. The Wee1 kinase is a major regulator of the G2/M checkpoint, and halts the cell cycle by adding a negative phosphorylation on CDK1 (Tyr15). Additionally, Wee1 has a function in safeguarding the genome integrity during DNA synthesis. To assess the role of Wee1 in development and progression of malignant melanoma we examined its expression in a panel of paraffin-embedded patient derived tissue of benign nevi and primary- and metastatic melanomas, as well as in agarose-embedded cultured melanocytes. We found that Wee1 expression increased in the direction of malignancy, and showed a strong, positive correlation with known biomarkers involved in cell cycle regulation: Cyclin A (p<0.0001), Ki67 (p<0.0001), Cyclin D3 (p?=?0.001), p21Cip1/WAF1 (p?=?0.003), p53 (p?=?0.025). Furthermore, high Wee1 expression was associated with thicker primary tumors (p?=?0.001), ulceration (p?=?0.005) and poor disease-free survival (p?=?0.008). Transfections using siWee1 in metastatic melanoma cell lines; WM239WTp53, WM45.1MUTp53 and LOXWTp53, further support our hypothesis of a tumor promoting role of Wee1 in melanomas. Whereas no effect was observed in LOX cells, transfection with siWee1 led to accumulation of cells in G1/S and S phase of the cell cycle in WM239 and WM45.1 cells, respectively. Both latter cell lines displayed DNA damage and induction of apoptosis, in the absence of Wee1, indicating that the effect of silencing Wee1 may not be solely dependent of the p53 status of the cells. Together these results reveal the importance of Wee1 as a prognostic biomarker in melanomas, and indicate a potential role for targeted therapy, alone or in combination with other agents.

Magnussen, Gry Irene; Holm, Ruth; Emilsen, Elisabeth; Rosnes, Anne Katrine Ree; Slipicevic, Ana; Fl?renes, Vivi Ann

2012-01-01

185

Potential Therapeutic Targets for Oral Cancer: ADM, TP53, EGFR, LYN, CTLA4, SKIL, CTGF, CD70  

PubMed Central

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.

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

2014-01-01

186

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

PubMed Central

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

Harris, K; Mant, J

2013-01-01

187

CARCINOGENIC POTENTIAL OF ROTENONE: SUBCHRONIC ORAL AND PERITONEAL ADMINISTRATION TO RATS AND CHRONIC DIETARY ADMINISTRATION TO SYRIAN GOLDEN HAMSTERS  

EPA Science Inventory

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

188

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

ERIC Educational Resources Information Center

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…

Blake, Christopher

2009-01-01

189

The change of electric potentials in the oral cavity after application of extremely low frequency pulsed magnetic field.  

PubMed

Electric potentials occurring in the oral cavity deserve attention as they may cause various diseases and subjective feelings, which are very difficult to treat. The aim of this study was to evaluate the electric potentials within the oral cavity in patients with metal fillings and metal prosthetic restorations, after using a pulsed electromagnetic field. The study was carried out on 84 patients. The Viofor JPS Classic device was used in the treatment. It generates a pulsed electromagnetic field with low induction of the extremely low frequency (ELF) range. Average values of electric potentials in the preliminary test were about the same in both groups; they were 148.8 mV and 145.5 mV. After another appliance of ELF fields there was found a steady decline in the average value of electric potentials in the study group. This decrease was statistically highly significant, while mean values of electric potentials in the control group were characterized by a slightly upward tendency. The obtained statistically significant reduction of electric potentials in the oral cavity of patients having metal fillings and metal prosthetic restorations, after application of the Viofor JPS Classic device, implies a huge impact of ELF pulsed electromagnetic field on inhibition of electrochemical processes, as well as on inhibition of dental alloy corrosion.  PMID:23687218

Skomro, Piotr; Lietz-Kijak, Danuta; Kijak, Edward; Bogdziewicz-Wa??sa, Olga; Opalko, Krystyna

2012-01-01

190

Identification of Tetranectin as a Potential Biomarker for Metastatic Oral Cancer  

PubMed Central

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

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

2010-01-01

191

Identification of tetranectin as a potential biomarker for metastatic oral cancer.  

PubMed

Lymph node involvement is the most important predictor of survival rates in patients with oral squamous cell carcinoma (OSCC). A biomarker that can indicate lymph node metastasis would be valuable to classify patients with OSCC for optimal treatment. In this study, we have performed a serum proteomic analysis of OSCC using 2-D gel electrophoresis and liquid chromatography/tandem mass spectrometry. One of the down-regulated proteins in OSCC was identified as tetranectin, which is a protein encoded by the CLEC3B gene (C-type lectin domain family 3, member B). We further tested the protein level in serum and saliva from patients with lymph-node metastatic and primary OSCC. Tetranectin was found significantly under-expressed in both serum and saliva of metastatic OSCC compared to primary OSCC. Our results suggest that serum or saliva tetranectin may serve as a potential biomarker for metastatic OSCC. Other candidate serum biomarkers for OSCC included superoxide dismutase, ficolin 2, CD-5 antigen-like protein, RalA binding protein 1, plasma retinol-binding protein and transthyretin. Their clinical utility for OSCC detection remains to be further tested in cancer patients. PMID:20957082

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

2010-01-01

192

The potential oral health impact of cost barriers to dental care: findings from a Canadian population-based study  

PubMed Central

Background Prior to the 2007/09 Canadian Health Measures Survey, there was no nationally representative clinical data on the oral health of Canadians experiencing cost barriers to dental care. The aim of this study was to determine the oral health status and dental treatment needs of Canadians reporting cost barriers to dental care. Methods A secondary data analysis of the 2007/09 Canadian Health Measures Survey was undertaken using a sample of 5,586 Canadians aged 6 to 79. Chi square tests were conducted to test the association between reporting cost barriers to care and oral health outcomes. Logistic regressions were conducted to identify predictors of reporting cost barriers. Results Individuals who reported cost barriers to dental care had poorer oral health and more treatment needs compared to their counterparts. Conclusions Avoiding dental care and/or foregoing recommended treatment because of cost may contribute to poor oral health. This study substantiates the potential likelihood of progressive dental problems caused by an inability to treat existing conditions due to financial barriers.

2014-01-01

193

Clinical and biochemical studies support smokeless tobacco's carcinogenic potential in the human oral cavity.  

PubMed

In 2007, the International Agency for Research on Cancer presented compelling evidence that linked smokeless tobacco use to the development of human oral cancer. Although these findings imply vigorous local carcinogen metabolism, little is known about levels and distribution of phase I, II, and III (drug egress) enzymes in human oral mucosa. In this study here, we integrated clinical data, and imaging and histopathologic analyses of an oral squamous cell carcinoma that arose at the site of smokeless tobacco quid placement in a patient. Immunoblot and immunohistochemical (IHC) analyses were used to identify tumor and normal human oral mucosal smokeless tobacco-associated metabolic activation and detoxification enzymes. Human oral epithelium contains every known phase I enzyme associated with nitrosamine oxidative bioactivation with approximately 2-fold interdonor differences in protein levels. Previous studies have confirmed approximately 3.5-fold interdonor variations in intraepithelial phase II enzymes. Unlike the superficially located enzymes in nonreplicating esophageal surface epithelium, IHC studies confirmed that oral mucosal nitrosamine metabolizing enzymes reside in the basilar and suprabasilar region, which notably is the site of ongoing keratinocyte DNA replication. Clearly, variations in product composition, nitrosamine metabolism, and exposure duration will modulate clinical outcomes. The data presented here form a coherent picture consistent with the abundant experimental data that link tobacco-specific nitrosamines to human oral cancer. PMID:24265177

Mallery, Susan R; Tong, Meng; Michaels, Gregory C; Kiyani, Amber R; Hecht, Stephen S

2014-01-01

194

Comparative Study of Expression of Smad3 in Oral Lichen Planus and Normal Oral Mucosa  

PubMed Central

Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa which is considered by the World Health Organization (WHO) as a premalignant condition. One step in malignant development is so called epithelial mesenchymal transition (EMT), a process whereby epithelial cells acquire mesenchymal characteristics. A factor known to induce EMT is the transforming growth factor-? (TGF-?), which uses the Smad proteins as mediators for its signaling. The aim of this study was to compare the expression of Smad 3 in Oral Lichen Planus and normal oral mucosa. This descriptive analytic study was performed on 30 patients with OLP (21 women and 9 men with mean age of 45.23± 2.44 years) and 20 normal oral mucosa (14 women and 6 men with mean age of 46.95± 2.21 years). The samples were studied by immunohistochemical staining. Data were analyzed with paired T-test and Wilcoxon test by SPSS software. Expression of Smad3 in OLP samples and normal oral mucosa was different. This difference was statistically significant (P<0.001). The apparently higher expression of Smad 3 in oral lichen planus compared to normal oral mucosa might help to discuss its higher potential for malignant transition.

Nafarzadeh, Shima; Ejtehadi, Samad; Amini Shakib, Pouyan; Fereidooni, Majid; Bijani, Ali

2013-01-01

195

Uterine smooth muscle tumors of uncertain malignant potential: diagnostic challenges and therapeutic dilemmas. Report of 2 cases and review of the literature.  

PubMed

Morphologically, there exist variants of uterine smooth muscle tumors that cannot be clearly interpreted and classified as benign or malignant. Because their behavior and clinical prognosis is also uncertain, the World Health Organization has termed these "smooth muscle tumors of uncertain malignant potential" (STUMP). Herein we describe 2 cases, present a review of the literature, and highlight the diagnostic challenges and therapeutic dilemmas associated with uterine STUMP in myomectomy specimens from women who wish to maintain or enhance their fertility. The clinical course of residual STUMP remains speculative. PMID:22546421

Vilos, George A; Marks, Jennifer; Ettler, Helen C; Vilos, Angelos G; Prefontaine, Michel; Abu-Rafea, Basim

2012-01-01

196

Disruption of transient receptor potential canonical channel 1 causes incomplete cytokinesis and slows the growth of human malignant gliomas.  

PubMed

Despite decades of research, primary brain tumors, gliomas, lack effective treatment options and present a huge clinical challenge. Particularly, the most malignant subtype, Glioblastoma multiforme, proliferates extensively and cells often undergo incomplete cell divisions, resulting in multinucleated cells. We now present evidence that multinucleated glioma cells result from the functional loss of transient receptor potential canonical 1 (TRPC1) channels, plasma membrane proteins involved in agonist-induced calcium entry and reloading of intracellular Ca(2+) stores. Pharmacological inhibition or shRNA mediated suppression of TRPC1 causes loss of functional channels and store-operated calcium entry in D54MG glioma cells. This is associated with reduced cell proliferation and, frequently, with incomplete cell division. The resulting multinucleated cells are reminiscent of those found in patient biopsies. In a flank tumor model, tumor size was significantly decreased when TRPC1 expression was disrupted using a doxycycline inducible shRNA knockdown approach. These results suggest that TRPC1 channels play an important role in glioma cell division most likely by regulating calcium signaling during cytokinesis. PMID:20544850

Bomben, Valerie C; Sontheimer, Harald

2010-08-01

197

Internalization with high targeting potential of mouse monoclonal antibody ONS-M21 recognizing human malignant glioma antigen.  

PubMed

In order to evaluate the targeting potential of mouse monoclonal antibody ONS-M21 recognizing a human astrocytoma- and medulloblastoma-associated antigen, the internalization ability of this antibody and the selective cytotoxicity in the toxin-conjugated form were examined. Internalization assay with 125I-labeled ONS-M21 showed that about 20% of the total radioactivities was detected in the cellular fraction of human medulloblastoma cell line ONS-76 cells and that the reaction reached a plateau level in 30 min. To examine the selective delivery capacity of a high molecular substance in place of 125I, an immunotoxin was prepared with ricin A chain and ONS-M21 via disulfide bonds. A cytotoxic effect against ONS-76 cells was found with [3H]thymidine incorporation assay using the immunotoxin, but not against antigen-negative HuH-7 and SW480 cells. These results suggest that ONS-M21 could effectively deliver toxins, chemotherapeutic agents or radionuclei to malignant glioma specifically. PMID:9619874

Shimizu, K; Park, K C; Tamura, K; Kishima, H; Kawata, H; Yoshimura, Y; Sekimori, Y; Miyao, Y; Hayakawa, T

1998-05-15

198

Malignant Potential of Cells Isolated from Lymph Node or Brain MĂ©tastases of Melanoma Patients and Implications for Prognosis1  

Microsoft Academic Search

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 métastases (A375-SM, TXM-1, DM-4) or from brain métastases (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

Ruo Dan Zhang; Janet E. Price; Gabriele Schackert; Kyogo Itoh; Isaiah J. Fidler

199

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

PubMed

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. PMID:23900869

Kiszka, K; Rudnicka-Sosin, L; Tomaszewska, R; Urba?czyk-Zawadzka, M; Krupi?ski, M; Pikul, P; Podsiad?o, K; Pasowicz, M; Vliegenthart, R; Oudkerk, M; Miszalski-Jamka, T

2013-06-01

200

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

PubMed Central

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

MATAYOSHI, SEN; CHIBA, SHUNMEI; LIN, YANFUI; ARAKAKI, KAZUNARI; MATSUMOTO, HIROFUMI; NAKANISHI, TAKAYA; SUZUKI, MIKIO; KATO, SEIYA

2013-01-01

201

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

PubMed Central

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 ?-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.

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

202

Biochemical markers in oral submucous fibrosis: A review and update  

PubMed Central

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.

Kamath, V V; Satelur, K; Komali, Y

2013-01-01

203

Induction of cyclooxygenase-2 signaling by Stomatococcus mucilaginosus highlights the pathogenic potential of an oral commensal.  

PubMed

Stomatococcus mucilaginosus is an oral commensal that has been occasionally reported to cause severe infections in immunocompromised patients. There is no information about the pathogenic role of S. mucilaginosus in airway infections. In a cohort of 182 subjects with bronchiectasis, we found that 9% were colonized with S. mucilaginosus in their lower airways by culture growth from bronchoalveolar lavage. To address the pathogenic potential of S.mucilaginosus, we developed a murine model of S. mucilaginosus lung infection. Intratracheal injection of S. mucilaginosus in C57BL/6 mice resulted in a neutrophilic influx with production of proinflammatory cytokines, chemokines, and lipid mediators, mainly PGE? with induction of cyclooxygenase-2 (COX-2) in the lungs. Presence of TLR2 was necessary for induction of COX-2 and production of PGE? by S. mucilaginosus. TLR2-deficient mice showed an enhanced clearance of S. mucilaginosus compared with wild-type mice. Administration of PGE? to TLR2(-/-) mice resulted in impaired clearance of S. mucilaginosus, suggesting a key role for COX-2-induced PGE? production in immune response to S. mucilaginosus. Mechanistically, induction of COX-2 in macrophages was dependent on the p38-ERK/MAPK signaling pathway. Furthermore, mice treated with S. mucilaginosus and Pseudomonas aeruginosa showed an increased mortality compared with mice treated with PA103 or S. mucilaginosus alone. Inhibition of COX-2 significantly improved survival in mice infected with PA103 and S. mucilaginosus. These data provide novel insights into the bacteriology and personalized microbiome in patients with bronchiectasis and suggest a pathogenic role for S. mucilaginosus in patients with bronchiectasis. PMID:24018272

Yuan, Zhihong; Panchal, Dipti; Syed, Mansoor Ali; Mehta, Hiren; Joo, Myungsoo; Hadid, Walid; Sadikot, Ruxana T

2013-10-01

204

Pharmacokinetics and potential advantages of a new oral solution of levothyroxine vs. other available dosage forms.  

PubMed

To better understand the pharmacokinetics and potential advantages of a levothyroxine oral solution vs. tablets and soft gel capsules.4 randomized, 2-treatment, single-dose (600 mcg levothyroxine), 2-way crossover bioequivalence studies in 84 healthy subjects were analyzed. Samples were collected before dosing and until 48-72?h post-dose to calculate noncompartmental baseline-adjusted pharmacokinetic parameters: maximum concentration, time to maximum concentration, and area-under-the-concentration-time-curve from 0 to 48?h and from 0 to 2?h.Mean pharmacokinetic parameters (±standard deviation) for tablets, capsules and solution, respectively, were: area-under-the-concentration-time-curve from 0 to 2?h (ng*h/mL)=68.4±32.8, 64.4±24.4, 99.1±22.7; area-under-the-concentration-time-curve from 0 to 48?h (ng*h/mL)=1?632±424, 1?752±445, 1?862±439; maximum concentration (ng/mL)=67.6±20.9, 68.0±15.9, 71.4±16.0; time of maximum concentration (hours)=2.25±0.99, 2.38±1.58, 1.96±1.07. Overall rate and extent of exposure were not statistically different between formulations, but a faster onset of absorption for the solution was suggested (greater area-under-the-concentration-time-curve from 0 to 2?h and faster time to maximum concentration by an average of 30?min).Levothyroxine rate and extent of exposure are similar between tested formulations. The solution appears however to reach systemic circulation quicker as dissolution is not needed before absorption starts. The solution's greater early exposure and a faster time to maximal concentration of around 30?min may be of benefit to minimize drug-food interactions and deserves further investigations. PMID:23154888

Yue, C S; Scarsi, C; Ducharme, M P

2012-12-01

205

Identification of miRNA-103 in the Cellular Fraction of Human Peripheral Blood as a Potential Biomarker for Malignant Mesothelioma - A Pilot Study  

PubMed Central

Background To date, no biomarkers with reasonable sensitivity and specificity for the early detection of malignant mesothelioma have been described. The use of microRNAs (miRNAs) as minimally-invasive biomarkers has opened new opportunities for the diagnosis of cancer, primarily because they exhibit tumor-specific expression profiles and have been commonly observed in blood of both cancer patients and healthy controls. The aim of this pilot study was to identify miRNAs in the cellular fraction of human peripheral blood as potential novel biomarkers for the detection of malignant mesothelioma. Methodology/Principal Findings Using oligonucleotide microarrays for biomarker identification the miRNA levels in the cellular fraction of human peripheral blood of mesothelioma patients and asbestos-exposed controls were analyzed. Using a threefold expression change in combination with a significance level of p<0.05, miR-103 was identified as a potential biomarker for malignant mesothelioma. Quantitative real-time PCR (qRT-PCR) was used for validation of miR-103 in 23 malignant mesothelioma patients, 17 asbestos-exposed controls, and 25 controls from the general population. For discrimination of mesothelioma patients from asbestos-exposed controls a sensitivity of 83% and a specificity of 71% were calculated, and for discrimination of mesothelioma patients from the general population a sensitivity of 78% and a specificity of 76%. Conclusions/Significance The results of this pilot study show that miR-103 is characterized by a promising sensitivity and specificity and might be a potential minimally-invasive biomarker for the diagnosis of mesothelioma. In addition, our results support the concept of using the cellular fraction of human blood for biomarker discovery. However, for early detection of malignant mesothelioma the feasibility of miR-103 alone or in combination with other biomarkers needs to be analyzed in a prospective study.

Weber, Daniel G.; Johnen, Georg; Bryk, Oleksandr; Jockel, Karl-Heinz; Bruning, Thomas

2012-01-01

206

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

PubMed Central

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

Knippels, Leon M J; Penninks, Andre H

2003-01-01

207

Human Calmodulin-Like Protein CALML3: A Novel Marker for Normal Oral Squamous Mucosa That Is Downregulated in Malignant Transformation.  

PubMed

Oral cancer is often diagnosed only at advanced stages due to a lack of reliable disease markers. The purpose of this study was to determine if the epithelial-specific human calmodulin-like protein (CALML3) could be used as marker for the various phases of oral tumor progression. Immunohistochemical analysis using an affinity-purified CALML3 antibody was performed on biopsy-confirmed oral tissue samples representing these phases. A total of 90 tissue specimens were derived from 52 patients. Each specimen was analyzed in the superficial and basal mucosal cell layers for overall staining and staining of cellular subcompartments. CALML3 was strongly expressed in benign oral mucosal cells with downregulation of expression as squamous cells progress to invasive carcinoma. Based on the Cochran-Armitage test for trend, expression in the nucleus and at the cytoplasmic membrane significantly decreased with increasing disease severity. Chi-square test showed that benign tissue specimens had significantly more expression compared to dysplasia/CIS and invasive specimens. Dysplasia/CIS tissue had significantly more expression than invasive tissue. We conclude that CALML3 is expressed in benign oral mucosal cells with a statistically significant trend in downregulation as tumorigenesis occurs. CALML3 may thus be a sensitive new marker for oral cancer screening. PMID:23935623

Brooks, Michael D; Bennett, Richard D; Weaver, Amy L; Sebo, Thomas J; Eckert, Steven E; Strehler, Emanuel E; Carr, Alan B

2013-01-01

208

Impact of palifermin on incidence of oral mucositis and healthcare utilization in children undergoing autologous hematopoietic stem cell transplantation for malignant diseases.  

PubMed

Palifermin has been demonstrated to decrease the incidence of severe oral mucositis in adults following TBI containing conditioning regimens prior to AHSCT. The impact of palifermin on the incidence of oral mucositis in children undergoing AHSCT has never been studied. We compared the effect of palifermin on the incidence of oral mucositis and supportive care in 58 children undergoing myeloablative AHSCT; 25 children received palifermin and 33 children did not receive palifermin (control arm). Oral mucositis was graded as per WHO criteria. The demographic characteristics were comparable between the two arms. Results comparing the palifermin vs. control arm showed that the incidence of grade III-IV oral mucositis was 20% vs. 42.4% (p = 0.072). The number of days patients received patient-controlled analgesia and total parenteral nutrition in the palifermin vs. control arm were 8.80 ± 8.39 vs. 8.30 ± 8.54 (p = 0.826) and 13.52 ± 11.32 vs. 11.55 ± 9.63 (p = 0.484), respectively. The average length of hospitalization in the palifermin vs. control arm was 31.44 ± 7.42 vs. 28.61 ± 10.38 (p = 0.252), respectively. In this study, we were unable to demonstrate a statistical difference in the incidence of oral mucositis and other supportive care needs or a decrease in hospital stay between the two arms. PMID:24823628

Vitale, Kelly M; Violago, Leah; Cofnas, Paige; Bishop, Jacquelyn; Jin, Zhezhen; Bhatia, Monica; Kung, Andrew L; George, Diane; Garvin, James; Satwani, Prakash

2014-03-01

209

Drug-Loaded Nanoparticle Systems And Adult Stem Cells: A Potential Marriage For The Treatment Of Malignant Glioma?  

PubMed Central

Despite all recent advances in malignant glioma research, only modest progress has been achieved in improving patient prognosis and quality of life. Such a clinical scenario underscores the importance of investing in new therapeutic approaches that, when combined with conventional therapies, are able to effectively eradicate glioma infiltration and target distant tumor foci. Nanoparticle-loaded delivery systems have recently arisen as an exciting alternative to improve targeted anti-glioma drug delivery. As drug carriers, they are able to efficiently protect the therapeutic agent and allow for sustained drug release. In addition, their surface can be easily manipulated with the addition of special ligands, which are responsible for enhancing tumor-specific nanoparticle permeability. However, their inefficient intratumoral distribution and failure to target disseminated tumor burden still pose a big challenge for their implementation as a therapeutic option in the clinical setting. Stem cell-based delivery of drug-loaded nanoparticles offers an interesting option to overcome such issues. Their ability to incorporate nanoparticles and migrate throughout interstitial barriers, together with their inherent tumor-tropic properties and synergistic anti-tumor effects make these stem cell carriers a good fit for such combined therapy. In this review, we will describe the main nanoparticle delivery systems that are presently available in preclinical and clinical studies. We will discuss their mechanisms of targeting, current delivery methods, attractive features and pitfalls. We will also debate the potential applications of stem cell carriers loaded with therapeutic nanoparticles in anticancer therapy and why such an attractive combined approach has not yet reached clinical trials.

Auffinger, Brenda; Morshed, Ramin; Tobias, Alex; Cheng, Yu; Ahmed, Atique U; Lesniak, Maciej S

2013-01-01

210

Proliferation and apoptosis markers in oral submucous fibrosis  

PubMed Central

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

Ranganathan, K; Kavitha, R

2011-01-01

211

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

Microsoft Academic Search

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

Thomas Mavrakanas; Henri Bounameaux

2011-01-01

212

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

PubMed

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 ?-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 ?-particles could enhance the potential of malignant transformation incidence in human bronchial epithelial cells through MAPK/Akt pathway. PMID:24746471

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

2014-05-01

213

Malignant hyperthermia.  

PubMed

Malignant hyperthermia refers to covert myopathies, which do not affect the individual during daily life activities, but may lead to life-threatening tachycardia, rigor, labile blood pressure and most importantly high-grade temperature when exposed to general anaesthesia. This conditions is mimicked by thyroid storm, neuroleptic malignant syndrome, phaeochromocytoma and sepsis. We present a presumptive case of malignant hyperthermia. PMID:14764260

Nasir, Khawaja Kamal; Zafar, Ayaz-bin; Mansoor, Faraz; Mushtaq, Sadia; Ahmad, Jawad; Khan, Imran Muhammad

2004-01-01

214

An insight into salivary markers in oral cancer  

PubMed Central

Salivary diagnostics has fascinated many researcheres and has been tested as a valuable tool in the diagnosis of many systemic conditions and for drug monitoring. Advances in the field of molecular biology, salivary genomics and proteomics have led to the discovery of new molecular markers for oral cancer diagnosis, therapeutics and prognosis. Oral cancer is a potentially fatal disease and the outcome of the treatment and prognosis largely depends on early diagnosis. Abnormal cellular products elucidated from malignant cells can be detected and measured in various body fluids including saliva and constitute tumor markers. This article discusses the various salivary tumor markers and their role in oral pre-cancer and cancer.

Krishna Prasad, Ramnarayan Belur; Sharma, Akhilesh; Babu, Harsha Mysore

2013-01-01

215

Intra-oral orthosis vs amitriptyline in chronic tension-type headache: a clinical and laser evoked potentials study  

PubMed Central

Background 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. Methods Eighteen patients with diagnosed CTTH participated in this open label, controlled study. A baseline evaluation was performed for clinical features, Total Tenderness Score (TTS) and a topographic analysis of LEPs obtained manually and the pericranial points stimulation in all patients vs. healthy subjects. Thereafter, patients were randomly assigned to a two-month treatment by either amitriptyline or intra-oral appliance. Results and discussion Both the intra-oral appliance and amitriptyline significantly reduced headache frequency. The TTS was significantly reduced in the group treated with the appliance. The amplitude of P2 response elicited by stimulation of pericranial zones showed a reduction after amitriptyline treatment. Both therapies were effective in reducing headache severity, the appliance with a prevalent action on the pericranial muscular tenderness, amitriptyline reducing the activity of the central cortical structures subtending pain elaboration Conclusion The results of this study may suggest that in CTTH both the interventions at the peripheral and central levels improve the outcome of headache.

de Tommaso, Marina; Shevel, Elliott; Pecoraro, Carla; Sardaro, Michele; Divenere, Daniela; Di fruscolo, Olimpia; Lamberti, Paolo; Livrea, Paolo

2006-01-01

216

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

PubMed Central

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

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

2011-01-01

217

Transcription Profiling Reveals Potential Mechanisms of Dysbiosis in the Oral Microbiome of Rhesus Macaques with Chronic Untreated SIV Infection  

PubMed Central

A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and “macaque versions” of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides.

Ocon, Susan; Murphy, Christina; Dang, Angeline T.; Sankaran-Walters, Sumathi; Li, Chin-Shang; Tarara, Ross; Borujerdpur, Niku; Dandekar, Satya; Paster, Bruce J.; George, Michael D.

2013-01-01

218

Oral exposure to drugs with immune-adjuvant potential induces hypersensitivity responses to the reporter antigen TNP-OVA.  

PubMed

Immune-mediated drug hypersensitivity reactions are important causes of black box warnings and drug withdrawals. Despite the high demand for preclinical screening tools, no validated in vitro or in vivo models are available. In the current study, we used a previously described oral administration model using trinitrophenyl-ovalbumin (TNP-OVA) as an antigen to report immuno-adjuvating effects of the analgesic drug acetaminophen (APAP) and its nonhepatotoxic regioisomer 3'-hydroxyacetanilide (AMAP), the antibiotic ofloxacin (OFLX), the antiepileptic drug carbamazepine (CMZ), and the antidiabetic drug metformin (MET). Furthermore, APAP and AMAP were tested in a popliteal lymph node assay (PLNA) combined with TNP-OVA as reporter antigen (RA). C3H/HeOuJ mice were dosed by oral gavage with diclofenac (DF), APAP, AMAP, OFLX, MET, or CMZ. On the first exposure day, the mice received an ip injection with TNP-OVA. Fifteen days later, they were ear challenged with TNP-OVA and delayed-type hypersensitivity (DTH) responses were assessed 24 h later. One week after challenge, the ear-draining lymph node was removed and TNP-specific antibody-secreting cells were determined. DF, APAP, CMZ, and OFLX showed a significant increase in DTH responses to ear injection with TNP-OVA, whereas AMAP and MET did not. C57BL/6 mice were slightly less responsive to APAP and DF after oral gavage, and importantly both AMAP and APAP were negative in the RA-PLNA. The present work shows that the oral exposure model using RA and the RA-PLNA may serve to screen the immune-adjuvant potential of new chemical entities during preclinical drug development. PMID:21402728

Kwast, Lydia M; Fiechter, Daniëlle; Hassing, Ine; Bleumink, Rob; Boon, Louis; Ludwig, Irene S; Pieters, Raymond H H

2011-06-01

219

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

PubMed Central

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

Palombo, Enzo A.

2011-01-01

220

Brain-penetrant, orally bioavailable microtubule-stabilizing small molecules are potential candidate therapeutics for Alzheimer's disease and related tauopathies.  

PubMed

Microtubule (MT) stabilizing drugs hold promise as potential treatments for Alzheimer's disease (AD) and related tauopathies. However, thus far epothilone D has been the only brain-penetrant MT-stabilizer to be evaluated in tau transgenic mice and in AD patients. Furthermore, this natural product exhibits potential deficiencies as a drug candidate, including an intravenous route of administration and the inhibition of the P-glycoprotein (Pgp) transporter. Thus, the identification of alternative CNS-active MT-stabilizing agents that lack these potential limitations is of interest. Toward this objective, we have evaluated representative compounds from known classes of non-naturally occurring MT-stabilizing small molecules. This led to the identification of selected triazolopyrimidines and phenylpyrimidines that are orally bioavailable and brain-penetrant without disruption of Pgp function. Pharmacodynamic studies confirmed that representative compounds from these series enhance MT-stabilization in the brains of wild-type mice. Thus, these classes of MT-stabilizers hold promise for the development of orally active, CNS-directed MT-stabilizing therapies. PMID:24992153

Lou, Kevin; Yao, Yuemang; Hoye, Adam T; James, Michael J; Cornec, Anne-Sophie; Hyde, Edward; Gay, Bryant; Lee, Virginia M-Y; Trojanowski, John Q; Smith, Amos B; Brunden, Kurt R; Ballatore, Carlo

2014-07-24

221

Potentiation of cisplatin and carboplatin cytotoxicity by amphotericin B in different human ovarian carcinoma and malignant peritoneal mesothelioma cells  

Microsoft Academic Search

An in vitro study of the combined cytotoxicity of either cisplatin (CDDP) or carboplatin and amphotericin B (AmB) was undertaken\\u000a on a set of different ovarian carcinoma (IGROVI, IGROVI-C10, OAW42) and peritoneal malignant mesothelioma (CFB-CARP1) cell\\u000a lines and ascitic cells freshly obtained from ovarian cancer patients so as to investigate the possibility of overcoming their\\u000a resistance to platinum compounds. Growth-inhibition

Laurent Poulain; François Sichel; Hubert Crouet; François Bureau; Pascal Gauduchon; Marc Gignoux; Jean-Yves Le Talaër

1997-01-01

222

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

Microsoft Academic Search

BackgroundPI3K\\/AKT signalling pathway is aberrantly active and plays a critical role for cell cycle progression of human malignant pleural mesothelioma (MMe) cells.AKT is one of the important cellular targets of perifosine, a novel bio-available alkylphospholipid that has displayed significant anti-proliferative activity in vitro and in vivo in several human tumour model systems and is currently being tested in clinical trials.MethodsWe

Giulia Pinton; Arcangela Gabriella Manente; Giovanni Angeli; Luciano Mutti; Laura Moro

2012-01-01

223

Salivary Markers for Oral Cancer Detection  

PubMed Central

Oral cancer refers to all malignancies that arise in the oral cavity, lips and pharynx, with 90% of all oral cancers being oral squamous cell carcinoma. Despite the recent treatment advances, oral cancer is reported as having one of the highest mortality ratios amongst other malignancies and this can much be attributed to the late diagnosis of the disease. Saliva has long been tested as a valuable tool for drug monitoring and the diagnosis systemic diseases among which oral cancer. The new emerging technologies in molecular biology have enabled the discovery of new molecular markers (DNA, RNA and protein markers) for oral cancer diagnosis and surveillance which are discussed in the current review.

Markopoulos, Anastasios K.; Michailidou, Evangelia Z.; Tzimagiorgis, Georgios

2010-01-01

224

Oral manifestations of hepatitis C virus infection  

PubMed Central

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.

Carrozzo, Marco; Scally, Kara

2014-01-01

225

Quantic molecular resonance scalpel and its potential applications in oral surgery.  

PubMed

Quantic molecular resonance is a new technique that applies high frequency waves suitable for many surgical fields. It is a remarkable advance from conventional electrosurgery, and consists of non-traumatic cutting of tissue and gentle coagulation. The cut is achieved by the explosion of infracellular and intracellular liquids, that resonate with a special frequency. The temperature of the cut area and surrounding tissues is less than 45 degrees C, so no thermal injury results. Coagulation is by denaturation of fibrinogen at 63 degrees C, and not at (conventional) higher temperatures. The result is the elimination of scar tissue or keloid, with considerable aesthetic benefits and reduction in postoperative swelling and pain. The quantic molecular resonance scalpel is a device that is suitable for oromaxillofacial surgery and related specialist areas (such as periodontology, implantology, and paediatric oral surgery). Other specialties (such as ear, nose, and throat, dermatology, aesthetic surgery, and veterinary surgery) could also benefit from this new technique. PMID:18495305

Vescovi, Paolo; Manfredi, Maddalena; Merigo, Elisabetta; Fornaini, Carlo; Rocca, Jean-Paul; Nammour, Samir; Bonanini, Mauro

2008-07-01

226

Synthesis and characterization of low surface energy fluoropolymers as potential barrier coatings in oral care.  

PubMed

A series of low surface energy fluorinated homopolymers and copolymers has been synthesized and characterized using thermal, optical, spectroscopic, and chromatographic techniques. Their utility as barrier technologies in oral care has been considered, and aqueous nanosuspensions of the materials have been deposited as films on model dental hard surfaces in the presence and absence of a salivary pellicle. Calcium hydroxyapatite has been used as a model for enamel, as has PMMA due to its widespread use in denture fabrication. Surface energy determinations, combined with XPS studies, have provided insights into the molecular-level organization at the surface of the film structures. Studies of solubility in supercritical carbon dioxide have identified the polymers that are suitable for processing in this medium. PMID:17647242

Churchley, David P; Barbu, Eugen; Ewen, Richard J; Shen, Zhihao; Kim, Yongchul; McHugh, Mark A; Zhang, Zhong Yi; Nevell, Thomas G; Rees, Gareth D; Tsibouklis, John

2008-03-15

227

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

PubMed

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

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

2013-11-01

228

CaN19 Expression in Benign and Malignant Hyperplasias of the Skin and Oral Mucosa: Evidence for a Role in Regenerative Differentiation  

Microsoft Academic Search

CaN19, a member of the S100 family of calcium-binding proteins, Is known to be “underexpressed” in cultured breast carcinoma-derived cell lines relative to their normal counterparts By Northern blotting, we confirm these results and find that CaN19 is also markedly “underexpressed” in several carcinoma-derivedcell lines of the skin, oral mucosa,and urogenital tract. However,exceptionsto the Inversecorrelation betweenCaN19expres slon and malignancyhave been

Longqing Xia; Stefan W. Stoll; Monica Liebert; Stephen P. Ethier; Thomas Carey; Ramon Esciamado

229

Epidemiology and Potential Preventative Measures for Viral Infections in Children With Malignancy and Those Undergoing Hematopoietic Cell Transplantation  

PubMed Central

In pediatric patients with malignancy and those receiving hematopoietic stem cell transplants, bacterial and fungal infections have been the focus of fever and neutropenia episodes for decades. However, improved diagnostic capabilities have revealed viral pathogens as a significant cause of morbidity and mortality. Because of limited effective antiviral therapies, prevention of viral infections is paramount. Pre-exposure and post-exposure prophylaxis and antiviral suppressive therapeutic approaches are reviewed. Additionally, infection control practices specific to this patient population are discussed. A comprehensive approach utilizing each of these can be effective at reducing the negative impact of viral infections.

Fisher, Brian T.; Alexander, Sarah; Dvorak, Christopher C.; Zaoutis, Theoklis E.; Zerr, Danielle M.; Sung, Lillian

2012-01-01

230

Expression of CXCR1 and CXCR2 receptors in malignant melanoma with different metastatic potential and their role in interleukin-8 (CXCL-8)-mediated modulation of metastatic phenotype  

Microsoft Academic Search

In the present study, we examined the autocrine\\/paracrine role of IL-8 in melanoma growth and metastasis by analyzing the\\u000a expression and functional significance of IL-8 receptors, CXCR1 and CXCR2 in human malignant melanoma cells with different\\u000a metastatic potential. CXCR1 and CXCR2 mRNA and protein levels were analyzed by reverse trannscriptase-based polymerase chain\\u000a reaction, immunohistochemistry, immunoprecipitation, flow cytometry and ligand binding

Michelle L. Varney; Aihua Li; Bhavana J. Dave; Corazan D. Bucana; Sonny L. Johansson; Rakesh K. Singh

2003-01-01

231

Expression of CXCR1 and CXCR2 receptors in malignant melanoma with different metastatic potential and their role in interleukin-8 (CXCL-8)-mediated modulation of metastatic phenotype.  

PubMed

In the present study, we examined the autocrine/paracrine role of IL-8 in melanoma growth and metastasis by analyzing the expression and functional significance of IL-8 receptors, CXCR1 and CXCR2 in human malignant melanoma cells with different metastatic potential. CXCR1 and CXCR2 mRNA and protein levels were analyzed by reverse trannscriptase-based polymerase chain reaction, immunohistochemistry, immunoprecipitation, flow cytometry and ligand binding assay in melanoma cells in vitro and xenografted in nude mice. Melanoma cells constitutively expressed CXCR1 and CXCR2 mRNA and protein. Highly metastatic A375SM cells expressed higher levels of CXCR1 and CXCR2 mRNA and protein in vitro and in vivo as compared to low metastatic A375P and non-metastatic SBC-2 melanoma cells. Treatment of SBC-2 and A375P cells with exogenously added recombinant IL-8 significantly enhanced their proliferation and invasive potential. Further neutralizing antibodies to CXCR1 and CXCR2 inhibited proliferation and invasive potential of unstimulated and IL-8-stimulated A375P cells. In summary, the data suggest that constitutive expression of CXCR1 and CXCR2 play an important role regulating the IL-8-mediated metastatic phenotype in human malignant melanoma cells. PMID:14713106

Varney, Michelle L; Li, Aihua; Dave, Bhavana J; Bucana, Corazan D; Johansson, Sonny L; Singh, Rakesh K

2003-01-01

232

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

PubMed

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

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

2011-08-01

233

Pathogenesis and therapeutic intervention of oral submucous fibrosis  

PubMed Central

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

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

2013-01-01

234

Pathogenesis and therapeutic intervention of oral submucous fibrosis.  

PubMed

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

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

2013-06-01

235

Positive predictive value for malignancy on surgical excision of breast lesions of uncertain malignant potential (B3) diagnosed by stereotactic vacuum-assisted needle core biopsy (VANCB): a large multi-institutional study in Italy.  

PubMed

Percutaneous core biopsy (CB) has been introduced to increase the ability of accurately diagnosing breast malignancies without the need of resorting to surgery. Compared to conventional automated 14 gauge needle core biopsy (NCB), vacuum-assisted needle core biopsy (VANCB) allows obtaining larger specimens and has recognized advantages particularly when the radiological pattern is represented by microcalcifications. Regardless of technical improvements, a small percentage of percutaneous CBs performed to detect breast lesions are still classified, according to European and UK guidelines, in the borderline B3 category, including a group of heterogeneous lesions with uncertain malignant potential. We aimed to assess the prevalence and positive predictive values (PPV) on surgical excision (SE) of B3 category (overall and by sub-categories) in a large series of non-palpable breast lesions assessed through VANCB, also comparison with published data on CB. Overall, 26,165 consecutive stereotactic VANCB were identified in 22 Italian centres: 3107 (11.9%) were classified as B3, of which 1644 (54.2%) proceeded to SE to establish a definitive histological diagnosis of breast pathology. Due to a high proportion of microcalcifications as main radiological pattern, the overall PPV was 21.2% (range 10.6%-27.3% for different B3 subtypes), somewhat lower than the average value (24.5%) from published studies (range 9.9%-35.1%). Our study, to date the largest series of B3 with definitive histological assessment on SE, suggests that B3 lesions should be referred for SE even if VANCB is more accurate than NCB in the diagnostic process of non-palpable, sonographically invisible breast lesions. PMID:21208804

Bianchi, S; Caini, S; Renne, G; Cassano, E; Ambrogetti, D; Cattani, M G; Saguatti, G; Chiaramondia, M; Bellotti, E; Bottiglieri, R; Ancona, A; Piubello, Q; Montemezzi, S; Ficarra, G; Mauri, C; Zito, F A; Ventrella, V; Baccini, P; Calabrese, M; Palli, D

2011-06-01

236

Malignant prolactinomas.  

PubMed

Six cases of malignant prolactinoma have been reported; an additional two cases are presented here and the literature is reviewed. Diagnosis rests upon evidence of metastasis rather than histological criteria per se. Cases have arisen from known adenomas, particularly the invasive type. Bromocriptine is a useful palliative. The features and treatment of malignant prolactinoma are discussed. PMID:1870674

Popovic, E A; Vattuone, J R; Siu, K H; Busmanis, I; Pullar, M J; Dowling, J

1991-07-01

237

The potential anticancer activity of extracts derived from the roots of Scutellaria baicalensis on human oral squamous cell carcinoma cells  

PubMed Central

Various herb products derived from plants have potent biological effects including anticancer activity. In the present study, the antitumor activity of a herbal product derived from the Scutellaria baicalensis (S. baicalensis) was examined, using in vitro assays in a human oral squamous cell carcinoma (OSCC) cell line. Results showed that S. baicalensis root extract at the concentration of 100 ?g/ml inhibited monolayer- and anchorage-independent growth in human OSCC cell lines, while not affecting the adhering abilities of cells. This suggested that it did not alter the expression of any of the adhesion receptors that mediate cell-extracellular matrix (ECM) interactions. The S. baicalensis root extract demonstrated potent cytostatic and apoptotic effects due to the downregulation of the cyclin-dependent kinase 4 expression and its partner cyclin D1, resulting in G1 arrest and poly (ADP-ribose) polymerase (PARP) cleavage. Additionally, the S. baicalensis root extract was found to have blocked vascular endothelial growth factor (VEGF)-induced migration and tube formation in human endothelial cells. Taken together, these results demonstrate that as a herbal product, the S. baicalensis root extract is a potential inhibitor of tumori- and angiogenesis and may be valuable in the development of pharmaceutical medications for the treatment of oral squamous cell carcinoma.

SATO, DAISUKE; KONDO, SEIJI; YAZAWA, KAZUNAGA; MUKUDAI, YOSHIKI; LI, CHUNNAN; KAMATANI, TAKAAKI; KATSUTA, HIDEYUKI; YOSHIHAMA, YASUTO; SHIROTA, TATSUO; SHINTANI, SATORU

2013-01-01

238

Construction and physiochemical characterisation of a multi-composite, potential oral vaccine delivery system (VDS).  

PubMed

An increasing human population requires a secure food supply and a cost effective, oral vaccine delivery system for livestock would help facilitate this end. Recombinant antigen adsorbed onto silica beads and coated with myristic acid, was released (?15% (w/v)) over 24 h at pH 8.8. At pH 2, the myristic acid acted as an enteric coating, protecting the antigen from a variety of proteases. The antigen adsorbed onto silica particles, coated in myristic acid had a conserved secondary structure (measured by circular dichroism (CD) spectroscopy) following its pH-triggered release. Small angle neutron scattering (SANS) was used to measure the thickness of the adsorbed antigen, finding that its adsorbed conformation was slightly greater than its solution radius of gyration, i.e. 120-160 Ĺ. The addition of myristic acid led to a further increase in particle size, with scattering data consistent with an acid thickness slightly greater than a monolayer of fully extended alkyl chains and a degree of hydration of around 50%. Whilst adsorbed onto the silica and coated in myristic acid, the protein was stable over 14 days at 42 °C, indicating a reduced need for cold chain storage. These data indicate that further investigation is warranted into the development of this technology. PMID:24680960

Pettit, Marie W; Dyer, Paul D R; Mitchell, John C; Griffiths, Peter C; Alexander, Bruce; Cattoz, Beatrice; Heenan, Richard K; King, Stephen M; Schweins, Ralf; Pullen, Frank; Wicks, Stephen R; Richardson, Simon C W

2014-07-01

239

Formulating SLMs as oral pulsatile system for potential delivery of melatonin to pediatric population.  

PubMed

The formulation development of melatonin (MLT) for infants and children with neurodevelopmental difficulties was fully investigated. This population have a higher prevalence of sleep disorders and present special challenges for drug administration and swallowing. To solve these issues, solid lipid microparticles (SLMs) were designed to obtain an oral flexible dosage form constituted by GRAS excipients and a free flow pulsatile delivery system for MLT, able to maintain its release through 8h. Three groups of SLMs were produced by spray congealing and characterized as regards particle size, morphology, flowability, solid state, drug content and release behavior. The SLMs manipulation with milk and yogurt and the MLT stability in these foods were also investigated. Microparticles with different excipient composition were selected to obtain a pulsatile release pattern over 8h. The final delivery platform displayed a prompt release from group I SLMs together with a lag phase of groups II and III SLMs, followed by a repeated MLT release from group II and a prolonged MLT release related to the last group. Finally, MLT was compatible and stable in milk and yogurt suggesting that microparticles sprinkled into food is acceptable for MLT administration to children unable to swallow capsules or tablets. PMID:24768728

Albertini, Beatrice; Di Sabatino, Marcello; Melegari, Cecilia; Passerini, Nadia

2014-07-20

240

Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma  

PubMed Central

Background Squamous cell carcinoma of the oral cavity (OSCC) is a common cancer form with relatively low 5-year survival rates, due partially to late detection and lack of complementary molecular markers as targets for treatment. Molecular profiling of head and neck cancer has revealed biological similarities with basal-like breast and lung carcinoma. Recently, we showed that 16 genes were consistently altered in invasive breast tumors displaying varying degrees of aggressiveness. Methods To extend our findings from breast cancer to another cancer type with similar characteristics, we performed an integrative analysis of transcriptomic and proteomic data to evaluate the prognostic significance of the 16 putative breast cancer-related biomarkers in OSCC using independent microarray datasets and immunohistochemistry. Predictive models for disease-specific (DSS) and/or overall survival (OS) were calculated for each marker using Cox proportional hazards models. Results We found that CBX2, SCUBE2, and STK32B protein expression were associated with important clinicopathological features for OSCC (peritumoral inflammatory infiltration, metastatic spread to the cervical lymph nodes, and tumor size). Consequently, SCUBE2 and STK32B are involved in the hedgehog signaling pathway which plays a pivotal role in metastasis and angiogenesis in cancer. In addition, CNTNAP2 and S100A8 protein expression were correlated with DSS and OS, respectively. Conclusions Taken together, these candidates and the hedgehog signaling pathway may be putative targets for drug development and clinical management of OSCC patients.

2014-01-01

241

Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation  

PubMed Central

Background Metastatic melanoma is a severe disease. Few experimental animal models of metastatic melanoma exist. MeLiM minipigs exhibit spontaneous melanoma. Cutaneous and metastatic lesions are histologically similar to human's. However, most of them eventually spontaneously regress. Our purpose was to investigate whether the MeLiM model could reveal markers of malignancy in human melanocytic proliferations. Results We compared the serial analysis of gene expression (SAGE) between normal pig skin melanocytes and melanoma cells from an early pulmonary metastasis of MeLiM minipigs. Tag identification revealed 55 regulated genes, including GNB2L1 which was found upregulated in the melanoma library. In situ hybridisation confirmed GNB2L1 overexpression in MeLiM melanocytic lesions. GNB2L1 encodes the adaptor protein RACK1, recently shown to influence melanoma cell lines tumorigenicity. We studied the expression of RACK1 by immunofluorescence and confocal microscopy in tissues specimens of normal skin, in cutaneous and metastatic melanoma developped in MeLiM minipigs and in human patients. In pig and human samples, the results were similar. RACK1 protein was not detected in normal epidermal melanocytes. By contrast, RACK1 signal was highly increased in the cytoplasm of all melanocytic cells of superficial spreading melanoma, recurrent dermal lesions and metastatic melanoma. RACK1 partially colocalised with activated PKC??. In pig metastases, additional nuclear RACK1 did not associate to BDNF expression. In human nevi, the RACK1 signal was low. Conclusion RACK1 overexpression detected in situ in human melanoma specimens characterized cutaneous and metastatic melanoma raising the possibility that RACK1 can be a potential marker of malignancy in human melanoma. The MeLiM strain provides a relevant model for exploring mechanisms of melanocytic malignant transformation in humans. This study may contribute to a better understanding of melanoma pathophysiology and to progress in diagnosis.

Egidy, Giorgia; Jule, Sophia; Bosse, Philippe; Bernex, Florence; Geffrotin, Claudine; Vincent-Naulleau, Silvia; Horak, Vratislav; Sastre-Garau, Xavier; Panthier, Jean-Jacques

2008-01-01

242

Diagnostic value of HBME-1, CD56, Galectin-3 and Cytokeratin-19 in papillary thyroid carcinomas and thyroid tumors of uncertain malignant potential.  

PubMed

Aim: We aimed to evaluate four immunohistochemical markers (HBME-1, Galectin-3, Cytokeratin-19 and CD56) used alone or in panels in a series of papillary thyroid carcinoma (PTC) and thyroid tumors of uncertain malignant potential (TT-UMP) cases. Materials and Methods: We performed an immunohistochemical analysis on a tissue micro-array of 11 PTCs [six classic (CPTC), five follicular variant (FVPTC)] and 31 TTs-UMP. A control group of 11 benign thyroid lesions÷tumors was also included. Results: CD56, whose expression is reduced or absent in thyroid carcinomas, was the most sensitive marker (81.8%), showing a "malignant" profile in 5÷6 CPTCs and 4÷5 FVPTCs. It was followed by HBME-1 (63.6% sensitivity). Cytokeratin-19 and Galectin-3 were the least sensitive antibodies (45.6%), but the most specific ones (100%). Three panels consisting of CD56 and÷or Cytokeratin-19÷Galectin-3 and HBME-1 and÷or CD56 reached the highest sensitivity (90.9%) and the highest negative predicting value (87.5 and 83.3, respectively). In TTs-UMP, Cytokeratin-19, Galectin-3, HBME-1 and CD56 stained negatively in most of the cases (90.3%, 83.9%, 87.1% and 61%, respectively) and no statistically significant differences compared to the benign thyroid lesions' immunoprofile could be observed. Conclusions: New panels of antibodies, consisting of CD56 and÷or Cytokeratin-19÷Galectin-3 and CD56 and÷or HBME-1 that were found to be highly sensitive for PTC in our study, are reported. Applying these panels to TTs-UMP seems also useful. Our results showed that these tumors have an immunoprofile similar to the benign thyroid lesions, suggesting that they are most likely to have a benign rather than a malignant biological behavior. PMID:24715165

Nechifor-Boil?, Adela; C?tan?, Ramona; Loghin, Andrada; Radu, Tatiana Georgiana; Borda, Angela

2014-01-01

243

Increased pleural fluid adenosine deaminase levels in patients with malignant pleural effusions: a potential predictor of talc pleurodesis outcome.  

PubMed

Chemical pleurodesis using various sclerosing agents is accepted palliative therapy for patients with recurrent, symptomatic, malignant pleural effusions (MPE). However, the utility of various clinical and biochemical parameters in predicting pleurodesis outcome is still controversial. The objective of this study was to investigate the relationship between pleural fluid adenosine deaminase (Pf-ADA) levels and talc pleurodesis outcomes, and to compare Pf-ADA levels to various other biochemical variables with respect to predicting talc pleurodesis outcome in patients with MPE. In this prospective trial, 60 consecutive patients with MPE were enrolled; 35 had malignant mesothelioma (MM) and 25 had metastatic pleural carcinoma (MPC). A complete response was achieved in 49 of 60 MPE patients (81.7%). The Pf-ADA, pH, and albumin levels in patients with successful pleurodesis were significantly higher than in those with unsuccessful pleurodesis (p values < 0.001, 0.036, 0.027, respectively). ROC curve analysis revealed that optimal differentiation between successful and unsuccessful pleurodesis could be achieved with cutoff points of 17.5 U/L for Pf-ADA (area under the curve = 0.873; sensitivity = 77.6%; specificity = 90.9%); >2.5 g/dl for albumin (area under the curve = 0.715; sensitivity = 85.4%; specificity = 54.5%); and >7.26 for pleural fluid pH (area under the curve = 0.703; sensitivity = 83.7%; specificity = 54.5%). In analysis of the subgroup, Pf-ADA were found to be a good marker for discrimination between successful and unsuccessful pleurodesis in patients with MM (p < 0.001) but not in the MPC group (p = 0.068). These results indicate that Pf-ADA levels could be considered predictors of the outcome of pleurodesis, especially in patient with MM. Furthermore, the present study also demonstrated that Pf-ADA level is a superior test to predict the outcome of pleurodesis compared to pleural fluid pH and albumin level. PMID:17952507

Yildirim, Huseyin; Metintas, Muzaffer; Ak, Güntülü; Erginel, Sinan; Alatas, Fusun; Kurt, Emel; Metintas, Selma; Ucgun, Irfan

2007-12-01

244

Oral Grape Seed Extract Inhibits Prostate Tumor Growth and Progression in TRAMP Mice  

Microsoft Academic Search

Prostate cancer chemoprevention is an alternative and potential strategy to control this malignancy. Herein, we evaluated the chemopreventive efficacy of grape seed extract (GSE) against prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice where animals were fed with GSE by oral gavage at 200 mg\\/kg body weight dose during 4 to 28 weeks of age. Our results

Komal Raina; Rana P. Singh; Rajesh Agarwal; Chapla Agarwal

245

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

PubMed Central

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

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

2013-01-01

246

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

PubMed Central

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

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

2012-01-01

247

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

NASA Astrophysics Data System (ADS)

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

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

2010-02-01

248

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

SciTech Connect

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

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

2009-10-01

249

Ras-Driven Transcriptome Analysis Identifies Aurora Kinase A as a Potential Malignant Peripheral Nerve Sheath Tumor Therapeutic Target  

PubMed Central

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.

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

250

Oral Complications in Hematopoietic Stem Cell Recipients: The Role of Inflammation  

PubMed Central

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.

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

251

Herpes - oral  

MedlinePLUS

... HSV-2 is spread to the mouth during oral sex, causing oral herpes. Herpes viruses spread easily. You ... if someone has oral herpes. Do not have oral sex if you have oral herpes, especially if you ...

252

Assessment of Oral Toxicity and Safety of Pentamethylchromanol (PMCol), A Potential Chemopreventative Agent, in Rats and Dogs  

PubMed Central

2,2,5,7,8-pentamethyl-6-chromanol (PMCol) was administered by gavage in rats for 28 days at dose levels of 0, 100, 500, and 2000 mg/kg/day. PMCol administration induced decreases in body weight gains and food consumption, hepatotoxicity (increased TBILI, ALB, ALT, TP; increased relative liver weights; increased T4 and TSH), nephrotoxicity (increased BUN and BUN/CREAT, histopathology lesions), effect on lipid metabolism (increased CHOL), anemia, increase in WBC counts (total and differential), coagulation (FBGN?and PT?) and hyperkeratosis of the nonglandular stomach in the 2000 mg/kg/day dose group (in one or both sexes). In the 500 mg/kg/day dose group, toxicity was seen to a lesser extent. In the 100 mg/kg/day dose group, only increased CHOL (females) was observed. To assess the toxicity of PMCol in male dogs it was administered orally by capsule administration for 28 days at dose levels of 0, 50, 200 and 800 mg/kg/day (4 male dogs/dose group). PMCol treatment at 800 mg/kg/day resulted in pronounced toxicity to the male dogs. Target organs of toxicity were liver and thymus. Treatment at 200 mg/kg/day resulted in toxicity consistent with slight adverse effect on the liver only. The results of the safety pharmacology study indicate that doses of 0, 50, 200 and 800 mg/kg administered orally did not have an effect on the QT interval, blood pressures and body temperatures following dosing over a 24-hour recording period. Under the conditions of this study, the no-observed-adverse effect level (NOAEL) for daily oral administration of PMCol by gavage for 28 days to male rats was 100 mg/kg/day and 50 mg/kg in male dogs. In female rats, the NOAEL was not established due to statistically significant and biologically meaningful increases in CHOL level seen in the 100 mg/kg/day dose group. The results of these studies indicated that administration of PMCol at higher dose levels resulted in severe toxicity in dogs and moderate toxicity in rats, however, administration at lower levels is considered to be less likely to result in toxicity following 28 days of exposure. Sex-related differences were seen in rats. Male rats appeared to have greater sensitivity to nephrotoxicity, while female animals had a greater incidence of hepatoxicity and changes in hematological parameters evaluated, especially at a dose of 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.

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

2010-01-01

253

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

Microsoft Academic Search

In recent years, attention has been focused on the possibility of utilizing DNA vaccines in fish aquaculture. A successful regime for intramuscular injection of naked DNA into fish has been developed and novel methods to deliver this DNA to fish are under investigation. The potential of chitosan as a polycationic gene carrier for oral administration has been explored since 1990s.

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

2008-01-01

254

Metastatic malignant melanoma of palate: A review of literature and report of an unusual case  

PubMed Central

Oral malignant melanoma is a rare tumor, accounting 0.8to 1.8 % of all oral malignancies. It occurs most commonly in Japanese and Negros. Radical surgery is mainstay of the treatment. Prognosis is very poor with 5 years survival rate. We present a case of malignant melanoma in a 55 years female, metastatizing to liver spleen and vertebrae.

Ram, Hari; Mohammad, Shadab; Husain, Nuzhat; Devi, Seema; Gupta, Prem Narayan

2010-01-01

255

Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review  

PubMed Central

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

Tanaka, Takuji; Tanaka, Mayu; Tanaka, Takahiro

2011-01-01

256

Multiple drug resistant, tumorigenic stem-like cells in oral cancer.  

PubMed

An in vitro cell line model was established to exemplify tumor stem cell concept in oral cancer. We were able to identify CD147 expressing fractions in SCC172 OSCC cell line with differing Hoechst dye efflux activity and DNA content. In vivo tumorigenic assay revealed three fractions enriched with stem-like cells capable of undergoing mesenchymal transition and a non-tumorigenic fraction. The regeneration potential and transition of one fraction to other imitated the phenotypic switch and functional disparities evidenced during oral tumor progression. Knowledge of these additional stem-like subsets will improve understanding of stem cell based oral epithelial tumor progression from normal to malignant lesions. PMID:23791883

Richard, Vinitha; Sebastian, Paul; Nair, Madhumathy G; Nair, Sree Narayanan; Malieckal, Tessy Thomas; Santhosh Kumar, T R; Pillai, M Radhakrishna

2013-09-28

257

Correlation of Trace Elemental Profiles in Blood Samples of Indian Patients with Leukoplakia and Oral Submucous Fibrosis  

Microsoft Academic Search

In order to ascertain possible correlation between alterations in trace elemental profile and the progression or regression\\u000a of two most common potentially malignant disorders affecting oral cavity, namely oral submucous fibrosis and leukoplakia,\\u000a blood from 60 patients from each group of patients as well from 30 healthy individuals was analyzed for elemental profiling\\u000a employing EDXRF technique. Out of the 16

J. G. Ray; Ranjan Ghosh; Debarati Mallick; Niharika Swain; Premdeep Gandhi; S. S. Ram; S. Selvaraj; A. Rathore; Sudarshan Mathummal; Anindita Chakraborty

258

Novel mucus-penetrating liposomes as a potential oral drug delivery system: preparation, in vitro characterization, and enhanced cellular uptake  

PubMed Central

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.

Li, Xiuying; Chen, Dan; Le, Chaoyi; Zhu, Chunliu; Gan, Yong; Hovgaard, Lars; Yang, Mingshi

2011-01-01

259

Oral mucosal health in liver transplant recipients and controls.  

PubMed

Immunosuppressive drugs and other medications may predispose patients to oral diseases. Data on oral mucosal health in recipients of liver transplantation (LT) are limited. We, therefore, recruited 84 LT recipients (64 with chronic liver disease and 20 with acute liver failure) for clinical oral examinations in a cross-sectional, case-control study. Their oral health had been clinically examined before transplantation. The prevalence of oral mucosal lesions (OMLs) was assessed in groups with different etiologies of liver disease and in groups with different immunosuppressive medications, and these groups were compared to controls selected from a nationwide survey in Finland (n = 252). Risk factors for OMLs were evaluated with logistic regression. OMLs were more frequent in LT recipients versus controls (43% versus 15%, P < 0.001), and the use of steroids raised the prevalence to 53%. Drug-induced gingival overgrowth was the single most common type of lesion, and its prevalence was significantly higher for patients using cyclosporine A (CSA; 29%) versus patients using tacrolimus (TAC; 5%, P = 0.007); the prevalence was even higher with the simultaneous use of calcium channel blockers and CSA (47%) or TAC (8%, P = 0.002). Lesions with malignant potential such as drug-induced lichenoid reactions, oral lichen planus-like lesions, leukoplakias, and ulcers occurred in 13% of the patients with chronic liver disease and in 6% of the controls. Every third patient with chronic liver disease had reduced salivary flow, and more than half of all patients were positive for Candida; this risk was higher with steroids. In conclusion, the high frequency of OMLs among LT recipients can be explained not only by immunosuppressive drugs but also by other medications. Because dry mouth affects oral health and OMLs may have the potential for malignant transformation, annual oral examinations are indicated. PMID:24142471

Helenius-Hietala, Jaana; Ruokonen, Hellevi; Grönroos, Lisa; Rissanen, Harri; Vehkalahti, Miira M; Suominen, Liisa; Isoniemi, Helena; Meurman, Jukka H

2014-01-01

260

Oral White Lesions Associated with Chewing Khat  

Microsoft Academic Search

INTRODUCTION: Khat is a cultivated plant whose leaves when chewed elevate mood. Unlike the chewing of betel nut, no association between the white oral mucosal lesions in khat users and oral malignancies has been reported. Chewing of khat has been documented in many countries and has increased with worldwide migration. The impact of chewing khat upon the oral mucosa is

Meir Gorsky; Joel B. Epstein; Harel Levi; Noam Yarom

2004-01-01

261

Development and characterization of a novel nanoemulsion drug-delivery system for potential application in oral delivery of protein drugs  

PubMed Central

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.

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

262

Selective inhibitors of phosphoinositide 3-kinase delta: modulators of B-cell function with potential for treating autoimmune inflammatory diseases and B-cell malignancies  

PubMed Central

The delta isoform of the p110 catalytic subunit (p110?) of phosphoinositide 3-kinase is expressed primarily in hematopoietic cells and plays an essential role in B-cell development and function. Studies employing mice lacking a functional p110? protein, as well as the use of highly-selective chemical inhibitors of p110?, have revealed that signaling via p110?-containing PI3K complexes (PI3K?) is critical for B-cell survival, migration, and activation, functioning downstream of key receptors on B cells including the B-cell antigen receptor, chemokine receptors, pro-survival receptors such as BAFF-R and the IL-4 receptor, and co-stimulatory receptors such as CD40 and Toll-like receptors (TLRs). Similarly, this PI3K isoform plays a key role in the survival, proliferation, and dissemination of B-cell lymphomas. Herein we summarize studies showing that these processes can be inhibited in vitro and in vivo by small molecule inhibitors of p110? enzymatic activity, and that these p110? inhibitors have shown efficacy in clinical trials for the treatment of several types of B-cell malignancies including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). PI3K? also plays a critical role in the activation, proliferation, and tissue homing of self-reactive B cells that contribute to autoimmune diseases, in particular innate-like B-cell populations such as marginal zone (MZ) B cells and B-1 cells that have been strongly linked to autoimmunity. We discuss the potential utility of p110? inhibitors, either alone or in combination with B-cell depletion, for treating autoimmune diseases such as lupus, rheumatoid arthritis, and type 1 diabetes. Because PI3K? plays a major role in both B-cell-mediated autoimmune inflammation and B-cell malignancies, PI3K? inhibitors may represent a promising therapeutic approach for treating these diseases.

Puri, Kamal D.; Gold, Michael R.

2012-01-01

263

Hematologic malignancies  

SciTech Connect

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

Hoogstraten, B.

1986-01-01

264

Loss of ELF3 immunoexpression is useful for detecting oral squamous cell carcinoma but not for distinguishing between grades of epithelial dysplasia.  

PubMed

Early diagnosis and targeted therapy are crucial to mitigating the morbidity and mortality of oral squamous cell carcinoma. Among the potentially malignant oral disorders, epithelial dysplasia has known association with malignant transformation, but defensible gradation of dysplasia severity presents unmet challenges. Published microarray data has denoted dysregulation of CLSP, ELF3, IFI44, USP18, and CXCL13 genes in potentially malignant oral disorders. The present study investigated the diagnostic potential of these gene products to grade oral epithelial dysplasia severity. Archived biopsies from independent patient cohorts comprised "training" (n=107) and "test" (n=278) sample sets. Immunoreactivity for candidate markers was determined in the "training" set of normal oral mucosa (NOM), mild dysplasia (MD), moderate to severe dysplasia, and oral squamous cell carcinoma (OSCC). The diagnostic potential of ELF3 immunoscoring to improve detection and severity gradation of epithelial dysplasia was assessed with the "test" set. A reciprocal relationship between disease severity and immunoreactivity score for CLSP and ELF3 was observed (MD/NOM to OSCC: P<.08, Mann-Whitney U test), whereas elevated IFI44 immunostaining was present for OSCC compared to MD/NOM (P<.08, Mann-Whitney U test). Loss of ELF3 immunostaining effectively distinguished OSCC from non-malignant tissues (sensitivity=0.81; specificity=0.56; area under the curve [AUC]=0.68) but did not distinguish dysplasia from NOM (sensitivity=0.55; specificity=0.40; AUC=0.47) or moderate to severe dysplasia from MD (sensitivity=0.63; specificity=0.51; AUC=0.57). The results confirm via immunohistochemistry the relevance of published CLSP, ELF3, and IFI44 (but not USP18 or CXCL13) gene expression data to potentially malignant oral lesion severity. Loss of ELF3 immunostaining discriminated OSCC from dysplasia but was unreliable for grading dysplasia severity. PMID:23643910

AbdulMajeed, Ahmad A; Dalley, Andrew J; Farah, Camile S

2013-08-01

265

Assessment of the carcinogenic potential of mitemcinal (GM-611): Increased incidence of malignant lymphoma in a rat carcinogenicity study  

SciTech Connect

Mitemcinal is an erythromycin derivative, which acts as an agonist of the motilin receptor. For assessment of the carcinogenicity of mitemcinal, we conducted a short-term carcinogenicity study in p53 (+/-) C57BL/6 mice and a 104-week carcinogenicity study in CD(SD)IGS rats. There was no evidence of a carcinogenic potential in mouse when administered for 26 consecutive weeks at levels up to 250 mg/kg/day. In the rat study, an increased incidence of lymphoma was noted in 5/60 males and 8/60 females of the high dose group (60 mg/kg/day) compared to 1/60 and 0/60 in control males and females, respectively, with statistical significance in females. Rat lymphomas include different immunomorphologic types (T- or B-cell lineage). Immunohistochemical analysis revealed that lymphomas from mitemcinal-treated rats and spontaneous cases were of T-cell lineage. The overall weight of evidence suggests that the incidence of spontaneous lymphoma was enhanced in the rat study. They also indicate that the increased incidence of lymphomas was based on a non-genotoxic effect with a threshold dose-response and that the tumorigenesis was based on the strain or species specificity of background factors. The high dose in the rat study is approximately 1600-fold higher (AUC) than that of the clinical dose, a sufficient margin of safety for the clinical dose. We conclude that the risk of carcinogenesis due to mitemcinal in humans can be considered to be minimal and is to represent an acceptable risk for the continued administration of mitemcinal to humans.

Fujii, Etsuko [Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka 412-8513 (Japan)], E-mail: fujiietk@chugai-pharm.co.jp; Kimura, Kazuya; Mizoguchi, Keiji; Kato, Atsuhiko; Takanashi, Hisanori [Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka 412-8513 (Japan); Itoh, Zen [Gunma University, Maebashi, Gunma 371-8512 (Japan); Omura, Satoshi [Kitasato Institute, Minato-ku, Tokyo 108-8642 (Japan); Suzuki, Masami [Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka 412-8513 (Japan)

2008-04-01

266

The R Enantiomer of the Antitubercular Drug PA-824 as a Potential Oral Treatment for Visceral Leishmaniasis  

PubMed Central

The novel nitroimidazopyran agent (S)-PA-824 has potent antibacterial activity against Mycobacterium tuberculosis in vitro and in vivo and is currently in phase II clinical trials for tuberculosis (TB). In contrast to M. tuberculosis, where (R)-PA-824 is inactive, we report here that both enantiomers of PA-824 show potent parasiticidal activity against Leishmania donovani, the causative agent of visceral leishmaniasis (VL). In leishmania-infected macrophages, (R)-PA-824 is 6-fold more active than (S)-PA-824. Both des-nitro analogues are inactive, underlining the importance of the nitro group in the mechanism of action. Although the in vitro and in vivo pharmacological profiles of the two enantiomers are similar, (R)-PA-824 is more efficacious in the murine model of VL, with >99% suppression of parasite burden when administered orally at 100 mg kg of body weight?1, twice daily for 5 days. In M. tuberculosis, (S)-PA-824 is a prodrug that is activated by a deazaflavin-dependent nitroreductase (Ddn), an enzyme which is absent in Leishmania spp. Unlike the case with nifurtimox and fexinidazole, transgenic parasites overexpressing the leishmania nitroreductase are not hypersensitive to either (R)-PA-824 or (S)-PA-824, indicating that this enzyme is not the primary target of these compounds. Drug combination studies in vitro indicate that fexinidazole and (R)-PA-824 are additive whereas (S)-PA-824 and (R)-PA-824 show mild antagonistic behavior. Thus, (R)-PA-824 is a promising candidate for late lead optimization for VL and may have potential for future use in combination therapy with fexinidazole, currently in phase II clinical trials against VL.

Patterson, Stephen; Wyllie, Susan; Stojanovski, Laste; Perry, Meghan R.; Simeons, Frederick R. C.; Norval, Suzanne; Osuna-Cabello, Maria; De Rycker, Manu

2013-01-01

267

Identification of an integrated mathematical model of standard oral glucose tolerance test for characterization of insulin potentiation in health.  

PubMed

Two new formulations, respectively denominated INT_M1 and INT_M2, of an integrated mathematical model to describe the glycemic and insulinemic responses to a 75 g oral glucose tolerance test (OGTT) are proposed and compared. The INT_M1 assumes a single compartment for the intestine and the derivative of a power exponential function for the gastric emptying rate, while, in the INT_M2, a nonlinear three-compartment system model is adopted to produce a more realistic, multiphase gastric emptying rate. Both models were implemented in a Matlab-based, two-step procedure for estimation of seven adjustable coefficients characterizing the gastric emptying rate and the incretin, insulin and glucose kinetics. Model behaviour was tested vs. mean plasma glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucose and insulin measurements from two different laboratories, where glycemic profiles observed during a 75 g OGTT were matched in healthy subjects (HC1- and HC2-group, respectively) by means of an isoglycemic intravenous glucose (I-IVG) infusion. Under the hypothesis of an additive effect of GLP-1 and GIP on insulin potentiation, our results demonstrated a substantial equivalence of the two models in matching the data. Model parameter estimates showed to be suitable markers of differences observed in the OGTT and matched I-IVG responses from the HC1-group compared to the HC2-group. Model implementation in our two-step parameter estimation procedure enhances the possibility of a prospective application for individualization of the incretin effect in a single subject, when his/her data are plugged in. PMID:21803437

Burattini, Roberto; Morettini, Micaela

2012-08-01

268

Preservation of high phenylalanine ammonia lyase activities in roots of Japanese Striped corn: a potential oral therapeutic to treat phenylketonuria.  

PubMed

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. PMID:24657198

López-Villalobos, Arturo; Lücker, Joost; López-Quiróz, Ana Angela; Yeung, Edward C; Palma, Kristoffer; Kermode, Allison R

2014-06-01

269

Enhanced oral bioavailability of a sterol-loaded microemulsion formulation of Flammulina velutipes, a potential antitumor drug  

PubMed Central

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 ?g · mL?1) and the standard anticancer drug, 5-fluorouracil (IC50 = 0.88 ?g · mL?1) exhibited strong in vitro antiproliferative activity against SGC cells, with IC50 > 30.0 ?g · mL?1; but the FVS performed poorly against LoVo cells (IC50 > 40.0 ?g · 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 ?g · 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.

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

270

Glucose tolerance factor extracted from yeast: oral insulin-mimetic and insulin-potentiating agent: in vivo and in vitro studies.  

PubMed

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. PMID:22172158

Weksler-Zangen, Sarah; Mizrahi, Tal; Raz, Itamar; Mirsky, Nitsa

2012-09-01

271

Clinical Significance of Altered Expression of ?-Catenin and E-Cadherin in Oral Dysplasia and Cancer: Potential Link with ALCAM Expression  

PubMed Central

Background Perturbations in cell adhesion molecules are linked to alterations in cadherin-catenin complexes and likely play major roles in invasion and metastasis; their impact on early precancerous stages remains yet unknown. We showed ALCAM overexpression in early oral lesions and its cytoplasmic accumulation in oral squamous cell carcinoma (OSCC) to be a predictor of disease progression and poor prognosis. This study tested the hypothesis that alterations in E-cadherin and ? -catenin expressions are early events in oral tumorigenesis, associated with disease prognosis, and correlate with perturbations in ALCAM expression. Methods Expressions of E-cadherin and ?-catenin were analyzed in the same cohort of 105 OSCCs, 76 oral lesions and 30 normal oral tissues by immunohistochemistry and correlated with clinicopathological parameters and prognosis. The effect of siRNA mediated ALCAM knockdown on E-cadherin and ? -catenin was determined using western blot, confocal microscopy and RT-PCR analysis in oral cancer cells. Results Significant loss of membranous E-cadherin and ?-catenin expression was observed from normal, hyperplasia, dysplasia to OSCCs (ptrend <0.001); and correlated with cytoplasmic ALCAM accumulation in OSCCs (p ?=?0.006). Multivariate analysis revealed ?-catenin membrane loss and ALCAM/?-cateninnuclear/cytoplasmic accumulation to be significant predictors for late clinical stage (p<0.001, OR?=?8.7; p?=?0.006, OR?=?9.9, respectively) and nodal metastasis (p?=?0.003, OR?=?3.8; p?=?0.025, OR?=?3.4 respectively). Cox’s regression showed E-cadherin membrane loss/ALCAM cytoplasmic expression [p<0.001; HR?=?4.8] to be independent adverse prognosticators in OSCCs. siRNA mediated silencing of ALCAM resulted in concurrent increase in E-cadherin and ?-catenin both at the transcript and protein levels. Conclusions Losses of E-cadherin and ?-catenin expressions are early events in oral tumorigenesis; their associations with aggressive tumor behavior and disease recurrence underscore their potential as prognostic markers. Correlation of loss of E-cadherin and ?-catenin with cytoplasmic ALCAM accumulation both in vitro and in in vivo suggests that these dynamic changes in cell adhesion system may play pivotal role in oral cancer.

DattaGupta, Siddhartha; Shukla, Nootan Kumar; Srivastava, Anurag; Walfish, Paul G.; Ralhan, Ranju

2013-01-01

272

Potential prevention: Aloe vera mouthwash may reduce radiation-induced oral mucositis in head and neck cancer patients.  

PubMed

In recent years, more head and neck cancer patients have been treated with radiotherapy. Radiation-induced mucositis is a common and dose limiting toxicity of radiotherapy among patients with head and neck cancers. Patients undergoing radiation therapy for head and neck cancer are also at increased risk of developing oral candidiasis. A number of new agents applied locally or systemically to prevent or treat radiation-induced mucositis have been investigated, but there is no widely accepted prophylactic or effective treatment for mucositis. Topical Aloe vera is widely used for mild sunburn, frostbites, and scalding burns. Studies have reported the beneficial effects of Aloe gel for wound healing, mucous membrane protection, and treatment of oral ulcers, in addition to antiinflammatory, immunomudulation, antifungal, scavenging free radicals, increasing collagen formation and inhibiting collagenase. Herein the author postulates that oral Aloe vera mouthwash may not only prevent radiation-induced mucositis by its wound healing and antiinflammatory mechanism, but also may reduce oral candidiasis of patients undergoing head and neck radiotherapy due to its antifungal and immunomodulatory properties. Hence, Aloe vera mouthwash may provide an alternative agent for treating radiation-induced oral mucositis and candidiasis in patients with head and neck cancers. PMID:22855041

Ahmadi, Amirhossein

2012-08-01

273

Exploring the potential of self-assembled mixed micelles in enhancing the stability and oral bioavailability of an acid-labile drug.  

PubMed

Oral delivery of many drugs is plagued with limited solubility and/or poor stability. This paper aimed to explore the performance of polymeric mixed micelles on solubilization, stabilization and bioavailability enhancement with stiripentol as model drug. Stiripentol-loaded mixed micelles were prepared by solvent-diffusion method: rapid dispersion of an ethanol solution containing stiripentol, monomethoxy poly(ethylene glycol)-b-poly(?-caprolactone) and sodium oleate into water. Stiripentol micelles were characterized by the particle size, entrapment efficiency, in vitro drug release, TEM, DSC and FTIR. The pharmacokinetic profile of stiripentol was determined in rats after oral administration of stiripentol micelles. The obtained stiripentol micelles were 44.2nm in size with an entrapment efficiency over 90%. It was shown that micelles substantially improved the solubility and gastric stability of stiripentol. The oral absorption of stiripentol was also enhanced to a great extent with a relative bioavailability of 157% and 444% to the commercial formulation (Diacomit®) and in-house suspensions. Mixed micelles assembled by di-block copolymer/sodium oleate exhibited a good potential in the improvement of drug stability and bioavailability. It should be a promising carrier for oral delivery of therapeuticals with solubility and stability issues. PMID:24956461

Zhang, Xingwang; Wang, Huan; Zhang, Tianpeng; Zhou, Xiaotong; Wu, Baojian

2014-10-01

274

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 Central

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. Most importantly, we are able to assess the RNA-binding activities of these putative translation-regulatory proteins in primary human breast surgical specimens, and begin to discern positive correlations between individual ITAFs and the malignant phenotype. Together with our previous findings, these new data provide further evidence that pathological dysregulation of IGF1R translational control may contribute to development and progression of human breast cancer, and breast metastasis in particular.

Blume, Scott W.; Jackson, Nateka L.; Frost, Andra R.; Grizzle, William E.; Shcherbakov, Oleg D.; Choi, Hyoungsoo; Meng, Zheng

2010-01-01

275

Immunohistochemical expression of p16 protein in oral squamous cell carcinoma and lichen planus.  

PubMed

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

Salehinejad, Jahanshah; Sharifi, Nourieh; Amirchaghmaghi, Maryam; Ghazi, Narges; Shakeri, Mohammad Taghi; Ghazi, Ala

2014-08-01

276

Oral Rinse as a Simpler Approach to Exfoliative Cytology: A Comparative Study  

PubMed Central

Background: Oral rinse is a novel method that can be used to detect dysplasia in potentially malignant disorders and malignant oral lesions in resource challenged areas. A study was undertaken to compare the quality of the normal smears prepared with the oral rinse and that of the wooden tongue spatula. Material and Methods: One hundred five normal subjects were selected for the study. Two smears were prepared from clinically normal mucosa using an oral rinse and further two smears were scraped from clinically normal buccal mucosa using a wooden spatula. Statistical Analysis: The smears were graded for cell yield, dispersion and cellular clarity on a three-point scale by two observers. The results were analyzed using Mann Whitney non parametric test. Results: The Oral rinse was found to be significantly more efficient than the wooden spatula, in terms of cell yield (p<0.0001), cell dispersion (p =.0052) and cellular detail (p<0.0001). Conclusion: The study showed that the Oral rinse is an effective method for use in exfoliative cytology of normal oral mucosa.

Mulki, Shaila; Shetty, Pushparaj; Pai, Prakash

2013-01-01

277

Malignant Peritoneal Mesothelioma  

Microsoft Academic Search

Malignant peritoneal mesothelioma (MPM) is an incurable disease. It represents approximately 15% of all mesotheliomas and\\u000a has a male predominance. It has a known relationship to asbestos, but most patients present with no known history of exposure.\\u000a Simian virus 40 (SV40) exposure is potentially another risk factor, although the relationship is not entirely supported. Patients\\u000a usually present with vague symptoms.

David P. Mangiameli; Steven K. Libutti; James F. Pingpank; H. Richard Alexander

278

Malignant hyperthermia.  

PubMed

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

Kim, Dong-Chan

2012-11-01

279

The Application of Vizilite in Oral Cancer  

PubMed Central

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

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

2013-01-01

280

PHYTOCHEMICAL DETERMINATION AND EXTRACTION OF MOMORDICA CHARANTIA FRUIT AND ITS HYPOGLYCEMIC POTENTIATION OF ORAL HYPOGLYCEMIC DRUGS IN DIABETES MELLITUS (NIDDM)  

Microsoft Academic Search

Abstract : Abstract : Abstract : Abstract : Momordica charantia (MC) fruit was subjected to phytochemical and pharmacological interaction studies with oral hypoglycemis in NIDDM patients. Phytochemical, chromatographical analysis and extraction of methanolic MC fruit soft (semi-solid form) in CCl 4 + C 6 H 6 solvent system yielded 15 diverse chemical constituents - alkaloids, glycosides, aglycone, tannin, sterol, phenol

ABHISHEK TONGIA; SUDHIR KUMAR TONGIA; MANGALA DAVE

2004-01-01

281

Interaction of brain fatty acid-binding protein with the polyunsaturated fatty acid environment as a potential determinant of poor prognosis in malignant glioma.  

PubMed

Malignant gliomas are the most common adult brain cancers. In spite of aggressive treatment, recurrence occurs in the great majority of patients and is invariably fatal. Polyunsaturated fatty acids are abundant in brain, particularly ?-6 arachidonic acid (AA) and ?-3 docosahexaenoic acid (DHA). Although the levels of ?-6 and ?-3 polyunsaturated fatty acids are tightly regulated in brain, the ?-6:?-3 ratio is dramatically increased in malignant glioma, suggesting deregulation of fundamental lipid homeostasis in brain tumor tissue. The migratory properties of malignant glioma cells can be modified by altering the ratio of AA:DHA in growth medium, with increased migration observed in AA-rich medium. This fatty acid-dependent effect on cell migration is dependent on expression of the brain fatty acid binding protein (FABP7) previously shown to bind DHA and AA. Increased levels of enzymes involved in eicosanoid production in FABP7-positive malignant glioma cells suggest that FABP7 is an important modulator of AA metabolism. We provide evidence that increased production of eicosanoids in FABP7-positive malignant glioma growing in an AA-rich environment contributes to tumor infiltration in the brain. We discuss pathways and molecules that may underlie FABP7/AA-mediated promotion of cell migration and FABP7/DHA-mediated inhibition of cell migration in malignant glioma. PMID:23981365

Elsherbiny, Marwa E; Emara, Marwan; Godbout, Roseline

2013-10-01

282

Lipomatous tumors of the oral mucosa: histomorphological, histochemical and immunohistochemical features.  

PubMed

We conducted a comprehensive study of all lipomatous tumors of the oral mucosa (1996-2008) accessioned at the Department of Oral Pathology, Tel Aviv University, collected demographic data and analyzed multiple histomorphological features. Furthermore, we examined the immunostaining of aP2 (adipocyte lipid binding protein) and the polarization colors of picrosirius red (PSR)-stained collagen fibers in order to test their potential in differentiating between benign and malignant tumors. All cases were immunohistochemically stained with aP2 antibody; only tumors with considerable collagenous stroma were selected for the PSR staining. A total of 77 tumors were included in the study, 91% benign and 9% malignant. Fibrolipoma (37.7%) and lipoma (36.4%) were the most frequent tumors. Atypical lipomatous tumor (ALT) was the only type of malignancy. The most common location for the benign tumors was the buccal mucosa and for ALT, the tongue. Histomorphological features characteristic of malignant tumors were occasionally present also in the benign entities. Expression of aP2 was similar in all tumors, while the polarization colors of the PSR-stained collagen fibers differed significantly between ALT and benign tumors (p<0.05). Benign and malignant tumors occasionally show overlapping histomorphological features that require a meticulous examination. PSR staining with polarization microscopy could aid in differentiating malignant from benign tumors in equivocal cases. PMID:21376375

Allon, Irit; Aballo, Sara; Dayan, Dan; Vered, Marilena

2011-12-01

283

[Malignant lymphomas].  

PubMed

Treatment outcome of malignant lymphomas has been improved since molecular targeted drugs including rituximab became clinically available. However, treatment for relapsed or refractory lymphoma has not been fully established. As second-line therapy for patients with relapsed/refractory follicular lymphoma or diffuse large B cell lymphoma, chemotherapy including alkylating agents or purine analogues, high-dose chemotherapy followed by autologous stem cell transplantation (SCT), and allogeneic SCT are usually selected. Recently, we can also select new therapies including new anti-CD20 monoclonal antibody (MoAb)(IMMU-106(hA20)), anti-CD22 MoAb (epratuzumab), and radioimmunotherapy including Y-90 ibritumomab and I-131 tositumomab. PMID:19461173

Yamaguchi, Yuko; Usui, Noriko

2009-05-01

284

Malignant mesothelioma  

PubMed Central

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.

Ahmed, Ishtiaq; Ahmed Tipu, Salman; Ishtiaq, Sundas

2013-01-01

285

Malignant mesothelioma.  

PubMed

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

Ahmed, Ishtiaq; Ahmed Tipu, Salman; Ishtiaq, Sundas

2013-11-01

286

The Problem of Atypical Neuroleptic Malignant Syndrome  

PubMed Central

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

Surber, Susan A.

2009-01-01

287

Oral Lesions and Lymphoproliferative Disorders  

PubMed Central

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.

Castellarin, P.; Pozzato, G.; Tirelli, G.; Di Lenarda, R.; Biasotto, M.

2010-01-01

288

Identification of an integrated mathematical model of standard oral glucose tolerance test for characterization of insulin potentiation in health  

Microsoft Academic Search

Two new formulations, respectively denominated INT_M1 and INT_M2, of an integrated mathematical model to describe the glycemic and insulinemic responses to a 75g oral glucose tolerance test (OGTT) are proposed and compared. The INT_M1 assumes a single compartment for the intestine and the derivative of a power exponential function for the gastric emptying rate, while, in the INT_M2, a nonlinear

Roberto Burattini; Micaela Morettini

289

Malignant hyperpyrexia  

PubMed Central

The history, clinical presentation, and management of malignant hyperpyrexia are presented. The aetiology seems to be associated with some inherited abnormality which affects the movement and binding of calcium ions in the sarcoplasmic reticulum, sarcoplasm, and mitochondria. Whether this is a primary muscular defect or secondary to some trophic neural influence is yet to be established. The subjects carrying the abnormal trait show evidence of a myopathy which is subclinical in most instances and revealed only by estimation of serum CPK or biopsy. In some families where the myopathy is clinically obvious there may be, in addition, a variety of musculoskeletal abnormalities. A plea is made for routine monitoring of temperature during anaesthesia and for procainamide or procaine to be readily available in all operating theatres. A history of anaesthetic deaths in a family calls for special care, and, if the serum CPK is elevated, suxamethonium and halothane are to be avoided. Families with orthopaedic and muscular abnormalities are at increased risk and should have estimation of serum CPK before surgery. As a bonus of this study it is suggested that serum CPK estimations be used to screen pigs for selective breeding and so eliminate the disease, which causes soft exudative pork. Images

Isaacs, Hyam; Barlow, M. B.

1973-01-01

290

The cultivable human oral gluten-degrading microbiome and its potential implications in coeliac disease and gluten sensitivity.  

PubMed

Coeliac 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 patients with coeliac disease. We found that the oral microbiome is a novel and rich source of gluten-degrading organisms. Here we report on the isolation and characterization of the cultivable resident oral microbes that are capable of cleaving gluten, with special emphasis on the immunogenic domains. Bacteria were obtained by a selective culturing approach and enzyme activities were characterized by: (i) hydrolysis of paranitroanilide-derivatized gliadin-derived tripeptide substrates; (ii) gliadin degradation in-gel (gliadin zymography); (iii) gliadin degradation in solution; (iv) proteolysis of the highly immunogenic ?-gliadin-derived 33-mer peptide. For selected 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 gastrointestinal tract. A cocktail of the most active oral bacteria, or their isolated enzymes, may offer promising new treatment modalities for coeliac disease. PMID:23714165

Fernandez-Feo, M; Wei, G; Blumenkranz, G; Dewhirst, F E; Schuppan, D; Oppenheim, F G; Helmerhorst, E J

2013-09-01

291

A fusion protein derived from plants holds promising potential as a new oral therapy for type 2 diabetes.  

PubMed

The incretin hormone glucagon-like peptide-1 (GLP-1) is recognized as a promising candidate for the treatment of type 2 diabetes (T2D), with one of its mimetics, exenatide (synthetic exendin-4) having already been licensed for clinical use. We seek to further improve the therapeutic efficacy of exendin-4 (Ex-4) using innovative fusion protein technology. Here, we report the production in plants a fusion protein containing Ex-4 coupled with human transferrin (Ex-4-Tf) and its characterization. We demonstrated that plant-made Ex-4-Tf retained the activity of both proteins. In particular, the fusion protein stimulated insulin release from pancreatic ?-cells, promoted ?-cell proliferation, stimulated differentiation of pancreatic precursor cells into insulin-producing cells, retained the ability to internalize into human intestinal cells and resisted stomach acid and proteolytic enzymes. Importantly, oral administration of partially purified Ex-4-Tf significantly improved glucose tolerance, whereas commercial Ex-4 administered by the same oral route failed to show any significant improvement in glucose tolerance in mice. Furthermore, intraperitoneal (IP) injection of Ex-4-Tf showed a beneficial effect in mice similar to IP-injected Ex-4. We also showed that plants provide a robust system for the expression of Ex-4-Tf, producing up to 37 ?g prEx-4-Tf/g fresh leaf weight in transgenic tobacco and 137 ?g prEx-4-Tf/g freshweight in transiently transformed leaves of N. benthamiana. These results indicate that Ex-4-Tf holds substantial promise as a new oral therapy for type 2 diabetes. The production of prEx-4-Tf in plants may offer a convenient and cost-effective method to deliver the antidiabetic medicine in partially processed plant food products. PMID:24373324

Choi, Jeehye; Diao, Hong; Feng, Zhi-Chao; Lau, Arthur; Wang, Rennian; Jevnikar, Anthony M; Ma, Shengwu

2014-05-01

292

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

NASA Astrophysics Data System (ADS)

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

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

2012-10-01

293

Oral and Cutaneous Melanoma: Similarities and Differences  

PubMed Central

Melanomas are malignant lesions stemming from the disorganized proliferation of melanocytes. This condition is more common on skin, but may also be detected in mucosa, such as in the oral cavity. The aim of the present study was to report similarities and differences between oral and cutaneous melanoma. Keywords Melanoma; Skin; Mouth; Diagnosis

Moreira, Rafaela Nogueira; Santos, Cassio Roberto Rocha; Lima, Nadia Lages; Verli, Flaviana Dornela; Marinho, Sandra Aparecida

2010-01-01

294

The Effect of Hyaluronic Acid on the Invasiveness of Malignant Glioma Cells : Comparison of Invasion Potential at Hyaluronic Acid Hydrogel and Matrigel  

PubMed Central

Objective Hyaluronidase (HAse), a degrading enzyme of hyaluronic acid (HA), is highly expressed in patients with malignant glioma. The purpose of this study was to verify whether HAse is related to the invasion of glioma cells. We also investigated if glioma cells with higher mobility in 2-dimensioal (2-D) method have also higher mobility at 3-dimensional (3-D) environment. Methods Malignant glioma cell lines (U87MG, U251MG, U343MG-A, and U373MG) were used, and their HAse expressions were evaluated by HA zymography. The migration ability was evaluated by simple scratch technique. The invasiveness of each cell lines was evaluated by Matrigel invasion assay and HA hydrogel invasion assay. In HA hydrogel invasion assay, colonies larger than 150 µm were regarded as positive ones and counted. Statistical analysis of migration ability and invasion properties of each cell lines was performed using t-test. Results In scratch test to examine migration ability of each cell lines, U87MG cells were most motile than others, and U343MG-A least motile. The HAse was expressed in U251MG and U343MG-A cell lines. However, U87MG and U373MG cell lines did not express HAse activity. In Matrigel invasion assay, the cell lines expressing HAse (U251MG and U343MG-A) were more invasive in the presence of HA than HAse deficient cell lines (U87MG and U373MG). In HA hydrogel invasion assay, the HAse-expressing cell lines formed colonies more invasively than HAse-deficient ones. Conclusion Malignant Glioma cells expressing HAse were more invasive than HAse-deficient ones in 3-dimensional environment. Therefore, it might be suggested that invasion of malignant gliomas is suppressed by inhibition of HAse expression or HA secretion. Additionally, the ability of 2-D migration and 3-D invasion might not be always coincident to each other in malignant glioma cells.

Jin, Shu-Guang; Jeong, Young-Il; Ryu, Hyang-Hwa; Jin, Yong-Hao; Kim, In-Young

2009-01-01

295

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

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 occurrence of IORN is an important long-term side effect of radiotherapy for oral cancers. From this data we only can conclude that a poor dental status, conventional fractionation and local tumour progression may enhance the risk of IORN which is in concordance with the literature.

2013-01-01

296

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

PubMed Central

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

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

2013-01-01

297

Telomerase activity in oral and maxillofacial tumors  

Microsoft Academic Search

Telomerase activity was measured in biopsy specimens as well as surgically resected tissues of 39 oral squamous cell carcinomas (SCCs), 22 oral leukoplakias, 13 normal oral mucosas, 12 malignant salivary gland tumors, 10 benign salivary tumors and five normal salivary gland tissues adjacent to tumors using a polymerase chain reaction (PCR)-based telomerase assay. Telomerase activity was detectable in 38.5% (5\\/13)

J. Liao; T. Mitsuyasu; K. Yamane; M. Ohishi

2000-01-01

298

Healthcare burden associated with the post-thrombotic syndrome and potential impact of the new oral anticoagulants.  

PubMed

Deep-vein thrombosis (DVT) can have a significant impact on a patient's life. In particular, the development of post-thrombotic syndrome as a long-term complication of DVT can have devastating consequences for the individual and impose a substantial economic burden on healthcare systems. Anticoagulants are the mainstay of DVT treatment; however, the current standard of care, a parenteral anticoagulant followed by a vitamin K antagonist, is associated with complex patient management, often resulting in suboptimal therapy. New, oral anticoagulants have been developed, and a direct thrombin inhibitor--dabigatran etexilate--and two direct Factor Xa inhibitors--rivaroxaban and apixaban--have completed and/or have ongoing phase III trials in the treatment of venous thromboembolism. These agents do not have the drawbacks of the vitamin K antagonists and hold promise for more effective treatment of DVT, possibly resulting in a reduction in the incidence of post-thrombotic syndrome. PMID:22077374

Prandoni, Paolo

2012-03-01

299

Aliskiren - an orally active renin inhibitor. Review of pharmacology, pharmacodynamics, kinetics, and clinical potential in the treatment of hypertension  

PubMed Central

The importance of renin-angiotensin-aldosterone system (RAAS) in diseases such as hypertension, congestive heart failure and chronic renal failure has long ago been recognized. It has also been established that inhibition of RAAS, using inhibitors of the angiotensin-converting enzyme (ACE) or angiotensin II receptor blockers (ARB), is an effective way to intervene with the pathogenesis of these disorders. Renin inhibitors block the RAAS at the highest level, at its origin, and might thus offer a new exciting approach for pharmacotherapy of arterial hypertension. Aliskiren is the first in a new class of orally active, non-peptide, low molecular weight renin inhibitors, and so far the only renin inhibitor that has progressed to phase III clinical trials. This review summarizes the available data on the pharmacokinetic and pharmacodynamic properties of aliskiren and its clinical development for treatment of arterial hypertension.

Allikmets, Kristina

2007-01-01

300

Viral and molecular aspects of oral cancer.  

PubMed

Squamous cell carcinoma (SCC) is the most common epithelial malignancy in the oral cavity. SCCs and their variants constitute over 90% of oral malignancies, and the disease is associated with poor prognosis. OSCC is a complex malignancy where environmental factors, virus infections, and genetic alterations most likely interact, and thus give rise to the malignant condition. Herein, we review the available literature regarding high-risk factors such as alcohol and tobacco usage; discuss the roles of human papillomaviruses (HPV), the Epstein-Barr virus, and the human herpes simplex virus (HSV); and evaluate several candidate genes associated with the condition: p53, p16(INK4) and p21(WAF1/CIPI), survivin, B-cell lymphoma-2 (BCL-2), keratins, Fibroblast growth factor 3 (FGF3), FGF4, FGF19, Oral cancer overexpressed gene 1 (ORAOV1), and Cyclin D1 (CCND1). PMID:23060540

Hillbertz, Nicolette Salmon; Hirsch, Jan-Michaél; Jalouli, Jamshid; Jalouli, Miranda M; Sand, Lars

2012-10-01

301

Gene Expression Patterns as Potential Molecular Biomarkers for Malignant Transformation in Human Keratinocytes Treated with MNNG, Arsenic, or a Metal Mixture  

Microsoft Academic Search

In previous studies, treatment with 1-methyl-3-nitro-1-ni- trosoguanidine (MNNG) enhanced malignant transformation of immortal human epidermal (RHEK-1) keratinocytes. In contrast, arsenic (As) alone or in a mixture of As, cadmium (Cd), chromium (Cr), and lead (Pb) inhibited this process. Microarray analysis showed unique gene expression patterns in RHEK-1 exposed to MNNG, As, or the metal mixture. From this analysis, we have

Dong-Soon Bae; Robert J. Handa; Raymond S. H. Yang; Julie A. Campain

2003-01-01

302

Understanding Carcinogenesis for Fighting Oral Cancer  

PubMed Central

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.

Tanaka, Takuji; Ishigamori, Rikako

2011-01-01

303

Accumulation of recombinant SARS-CoV spike protein in plant cytosol and chloroplasts indicate potential for development of plant-derived oral vaccines.  

PubMed

Plants are promising candidates as bioreactors for the production of oral recombinant proteins in the biopharmaceutical industry. As an initial step toward provision of an oral vaccine against the severe acute respiratory syndrome coronavirus (SARS-CoV), we have expressed a partial spike (S) protein of SARS-CoV in the cytosol of nuclear-transformed plants and in the chloroplasts of plastid-transformed plants. In the construction of both nuclear and plastid transformation vectors, a 2-kilobase nucleotide sequence encoding amino acids 1-658 of the SARS-CoV spike protein (S1) was modified with nucleotide changes, but not amino acid changes, to optimize codon usage for expression in plants. To investigate the subcellular localization of S1 during transient expression in tobacco leaves, a translational fusion consisting of S1 and the green fluorescent protein (GFP) was generated. Following agroinfiltration of tobacco leaves, analysis by laser confocal scanning microscopy revealed that the S1:GFP fusion protein was localized to the cytosol. In stable transgenic tobacco plants and lettuce plants generated by Agrobacterium-mediated transformation, tobacco and lettuce leaves were observed to express the S1 at high levels from the Cauliflower Mosaic Virus 35S promoter with Northern blot analysis. When the S1 was expressed in transplastomic tobacco, S1 messenger RNA and its corresponding protein were detected on Northern and Western blot analyses, respectively. Our results demonstrate the feasibility of producing S1 in nuclear- and chloroplast-transformed plants, indicating its potential in subsequent development of a plant-derived and safe oral recombinant subunit vaccine against the SARS-CoV in edible plants. PMID:16946403

Li, Hong-Ye; Ramalingam, Sathishkumar; Chye, Mee-Len

2006-09-01

304

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

PubMed

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

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

2013-06-01

305

Discovery of orally active carboxylic acid derivatives of 2-phenyl-5-trifluoromethyloxazole-4-carboxamide as potent diacylglycerol acyltransferase-1 inhibitors for the potential treatment of obesity and diabetes.  

PubMed

Diacylglycerol acyltransferase-1 (DGAT-1) is the enzyme that catalyzes the final and committed step of triglyceride formation, namely, the acylation of diacylglycerol with acyl coenzyme A. DGAT-1 deficient mice demonstrate resistance to weight gain on high fat diet, improved insulin sensitivity, and reduced liver triglyceride content. Inhibition of DGAT-1 thus represents a potential novel approach for the treatment of obesity, dyslipidemia, and metabolic syndrome. In this communication, we report the identification of the lead structure 6 and our lead optimization efforts culminating in the discovery of potent, selective, and orally efficacious carboxylic acid derivatives of 2-phenyl-5-trifluoromethyloxazole-4-carboxamides. In particular, compound 29 (DGAT-1 enzyme assay, IC(50) = 57 nM; CHO-K1 cell triglyceride formation assay, EC(50) = 0.5 ?M) demonstrated dose dependent inhibition of weight gain in diet induced obese (DIO) rats (0.3, 1, and 3 mg/kg, p.o., qd) during a 21-day efficacy study. Furthermore, compound 29 demonstrated improved glucose tolerance determined by an oral glucose tolerance test (OGTT). PMID:21413799

Qian, Yimin; Wertheimer, Stanley J; Ahmad, Mushtaq; Cheung, Adrian Wai-Hing; Firooznia, Fariborz; Hamilton, Matthew M; Hayden, Stuart; Li, Shiming; Marcopulos, Nicholas; McDermott, Lee; Tan, Jenny; Yun, Weiya; Guo, Liang; Pamidimukkala, Anjula; Chen, Yingsi; Huang, Kuo-Sen; Ramsey, Gwendolyn B; Whittard, Toni; Conde-Knape, Karin; Taub, Rebecca; Rondinone, Cristina M; Tilley, Jefferson; Bolin, David

2011-04-14

306

Reflectance confocal microscope for imaging oral tissues in vivo, potentially with line scanning as a low-cost approach for clinical use  

NASA Astrophysics Data System (ADS)

Reflectance confocal microscopy with a line scanning approach potentially offers a smaller, simpler and less expensive approach than traditional methods of point scanning for imaging in living tissues. With one moving mechanical element (galvanometric scanner), a linear array detector and off-the-shelf optics, we designed a compact (102x102x76mm) line scanning confocal reflectance microscope (LSCRM) for imaging human tissues in vivo in a clinical setting. Custom-designed electronics, based on field programmable gate array (FPGA) logic has been developed. With 405 nm illumination and a custom objective lens of numerical aperture 0.5, lateral resolution was measured to be 0.8 um (calculated 0.64 um). The calculated optical sectioning is 3.2 um. Preliminary imaging shows nuclear and cellular detail in human skin and oral epithelium in vivo. Blood flow is also visualized in the deeper connective tissue (lamina propria) in oral mucosa. Since a line is confocal only in one dimension (parallel) but not in the other, the detection is more sensitive to multiply scattered out of focus background noise than in the traditional point scanning configuration. Based on the results of our translational studies thus far, a simpler, smaller and lower-cost approach based on a LSCRM appears to be promising for clinical imaging.

Peterson, Gary; Abeytunge, Sanjeewa; Eastman, Zachary; Rajadhyaksha, Milind

2012-02-01

307

A malignant itch.  

PubMed Central

We report an unusual presentation of a previously healthy three-year-old Chinese girl with a four-week history of apparently unexplained generalized intense itch. She had no past history of atopy or xerosis. Despite the severe itch, she had only minimal scratch marks on her right gluteal region but no flexural involvement. The girl was treated as having scabies and eczema and with oral antihistamines by various dermatologists without much improvement. She subsequently presented to a regional hospital with right hip pain and fever. Radiological and histopathological investigations confirmed that she had a peripheral T-cell lymphoma. The itch pattern prior to and following chemotherapy, as documented by the DigiTrac wrist-held movement monitor, showed a dramatic reduction of her nocturnal itch. The pattern was also very different from that of atopic dermatitis in that the scratching was of much higher intensity but lower frequency. Intractable pruritus associated with a peripheral T-cell lymphoma has not been previously reported in the pediatric literature. This report serves to alert clinicians of the gold paradigm that in a patient with an unexplained generalized itch, lymphoma and other malignancies must be considered. Images Figure 1 Figure 2 Figure 3

Hon, Kam-lun Ellis; Lam, Man-chin Adrian; Leung, Ting-fan; Chik, Ki-wai; Leung, Alexander K. C.

2006-01-01

308

Potential Risk Factors for Cutaneous Squamous Cell Carcinoma include Oral Contraceptives: Results of a Nested Case-Control Study  

PubMed Central

Recently, a population-based case-control study observed a 60% increased odds ratio (OR) for cutaneous squamous cell carcinoma (SCC) among women who had ever used oral contraceptives (OCs) compared with non users (95% confidence interval (CI) = 1.0–2.5). To further characterize the putative association between OC use and SCC risk, we conducted a nested case-control study using a large retrospective cohort of 111,521 Kaiser Permanente Northern California members. Multivariable conditional logistic regression was used to estimate ORs and CIs adjusting for known and hypothesized SCC risk factors. Pre-diagnostic OC use was associated with a statistically significant increased OR for SCC in univariate analysis (OR = 2.4, CI = 1.2–4.8), with borderline statistical significance in multivariable analysis (CI = 2.0, CI = 0.91–4.5). Given the high incidence of SCC in the general population and the prevalent use of OCs among women in the United States, there is a need for more large, carefully designed epidemiologic studies to determine whether the observed association between OC use and SCC can be replicated and to better understand the etiologic basis of an association if one exists.

Asgari, Maryam M.; Efird, Jimmy T.; Warton, E. Margaret; Friedman, Gary D.

2010-01-01

309

The BRCA2 gene is a potential molecular target during 5-fluorouracil therapy in human oral cancer cells.  

PubMed

5-Fluorouracil (5-FU) is widely used in clinical cancer therapy. It is commonly used either alone or in combination with other drugs and/or radiation for head and neck, and other types of cancers. 5-FU induces DNA double-strand breaks (DSBs). Inhibition of the repair of 5-FU-induced DSBs may improve the therapeutic response in many tumors to this anticancer agent. The aim of the present study was to further our understanding of the pathways which are involved in the repair of 5-FU-induced DSBs. Cell survival after drug treatment was examined with colony forming assays using Chinese hamster lung fibroblast cells or Chinese hamster ovary cell lines which are deficient in DSB repair pathways involving the homologous recombination repair-related genes BRCA2 and XRCC2, and the non-homologous end joining repair-related genes DNA-PKcs and Ku80. It was found that BRCA2 was involved in such repair, and may be effectively targeted to inhibit the repair of 5-FU-induced damage. Observations showed that knockdown of BRCA2 using small interference RNA suppression increased the sensitivity to 5-FU of human oral cancer cell lines (SAS and HSC3). These findings suggest that downregulation of BRCA2 may be useful for sensitizing tumor cells during 5-FU chemotherapy. PMID:24627042

Nakagawa, Yosuke; Kajihara, Atsuhisa; Takahashi, Akihisa; Kondo, Natsuko; Mori, Eiichiro; Kirita, Tadaaki; Ohnishi, Takeo

2014-05-01

310

Improved stability and antidiabetic potential of insulin containing folic acid functionalized polymer stabilized multilayered liposomes following oral administration.  

PubMed

The present study reports the folic acid (FA) functionalized insulin loaded stable liposomes with improved bioavailability following oral administration. Liposomes were stabilized by alternating coating of negatively charged poly(acrylic acid) (PAA) and positively charged poly(allyl amine) hydrochloride (PAH) over liposomes. Furthermore, folic acid was appended as targeting ligand by synthesizing folic acid-poly(allyl amine) hydrochloride conjugate. The insulin entrapped within the freeze-dried formulation was found stable both chemically as well as conformationally and developed formulation exhibited excellent stability in simulated biological fluids. Caco-2 cell and ex vivo intestinal uptake studies revealed higher uptake of folic acid functionalized layersomes in comparison with their plain counterparts. In vivo pharmacodynamic and pharmacokinetic studies further revealed almost double hypoglycemia and approximately 20% relative bioavailability in comparison with subcutaneously administered standard insulin solution. Overall the proposed strategy is expected to contribute significantly in the field of designing ligand-anchored, polyelectrolyte-based stable systems in drug delivery. PMID:24283460

Agrawal, Ashish Kumar; Harde, Harshad; Thanki, Kaushik; Jain, Sanyog

2014-01-13

311

[Malignant gliomas].  

PubMed

Glial tumors represent 2000 to 3000 new cases per year in France and 75% of them are of high grade. Recent understanding of the molecular biology of these tumors revealed the importance of 1p19q codeletion and mgMT promotor methylation. Radiotherapy also recently evolved with the progress in medical imaging which allows a better definition of the target volumes. Even modest, therapeutic progress is based on chemoradiotherapy with temozolomide and on the development of non-coplanar conformational radiotherapy. Knowledge and precise evaluation of potential late effects of our treatments is necessary due to actual improvement of survival with chemoradiotherapy in glioblastoma. PMID:21129657

Haberer, S; Assouline, A; Mazeron, J-J

2010-11-01

312

Investigation of the oral infections and manifestations seen in patients with advanced cancer  

PubMed Central

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.

Xu, Lihua; Zhang, Hualin; Liu, Jinsong; Chen, Xiaowei

2013-01-01

313

Malignant or Accelarated Hypertension  

PubMed Central

Malignant or accelarated hypertension is a life-threatening medical emergency that is a possible complication of practically any hypertensive disorder. If not promptly treated it can cause severe, rapidly progressive target-organ damage and death. While the histo-pathologic features of malignant hypertension are well recognized, the pathogenesis of the associated vascular lesions and the transition from a benign to a malignant phase are unclear. With adequate control of hypertension, progression to the accelarated or malignant phase can be prevented. Moreover, promptly and effectively reducing the blood pressure during the malignant phase can prevent, minimize or even reverse serious target organ injury. Malignant hypertension, therefore, is both preventable and treatable.

Vaziri, N. D.

1984-01-01

314

Histological and molecular aspects of oral squamous cell carcinoma (Review)  

PubMed Central

Oral squamous cell carcinoma (OSCC) represents 95% of all forms of head and neck cancer, and over the last decade its incidence has increased by 50%. Oral carcinogenesis is a multistage process, which simultaneously involves precancerous lesions, invasion and metastasis. Degradation of the cell cycle and the proliferation of malignant cells results in the loss of control mechanisms that ensure the normal function of tissues. The aim of the current review is to present the histopathological features of OSCC, including potentially malignant changes, the international classification of tumors, the tumor invasion front and tumor biomarkers (Ki-67, p53, homeobox genes and collagen type IV), as well as the tumor microenvironment and function of cancer-associated fibroblasts in the most common type of oral cancer that is encountered by dental surgeons. In OSCC, associations have been identified between the proliferation, basal lamina degradation and connective tissue modulation. Therefore, the comparison of these factors with the survival time of OSCC patients from the histopathological diagnosis is of interest.

RIVERA, CESAR; VENEGAS, BERNARDO

2014-01-01

315

Is 1,25-dihydroxyvitamin D3 receptor expression a potential Achilles' heel of CD44+ oral squamous cell carcinoma cells?  

PubMed

The aim of this study was to analyse the expression of 1,25-dihydroxyvitamin D3 receptor (VDR) in oral cancers are squamous cell carcinomas (OSCC) to evaluate whether oral tissue may be a new potential target for biologically active 1,25-(OH)2D3 or its analogues. Expression of VDR was analysed in OSCC specimen (n=191) and cancer cell lines (BICR3, BICR56) by immunohistochemistry, real-time polymerase chain reaction (RT-PCR) analysis, and Western blotting. Scanned images were digitally analysed using ImageJ and the immunomembrane plug-in. VDR expression on protein level was correlated with proliferation marker Ki-67, clinical characteristics and impact on survival. VDR was co-labelled with CD44 and Ki-67 in double labeling experiments. Expression subgroups were identified by receiver operating characteristics (ROC) analysis. Low VDR expression was significantly associated with recurrence of the tumour. Multivariate analysis demonstrated low VDR expression as an independent prognostic factor (p=0.0005). Immunohistochemical double staining revealed VDR expression by CD44+ cancer cells. An inverse correlation of VDR+ expressing cancer cells with Ki-67 has been found, which was indicated by immunofluorescence double labeling. VDR specificity was confirmed by Western blot and RT-PCR analysis. For the first time, our study provides evidence that decreased VDR expression in OSCC might be associated with tumour relapse. Tumour cells of a putative CD44+ cancer stem cell compartment express VDR indicating a potential Achilles' heel for the treatment of OSCC although, our results do not allow any conclusion on the function of VDR. Adjuvant chemoprevention by using 1,25-(OH)2D3 or its analogues can be a successful tool targeting adjuvant residual tumour cells and will likely help therapeutic optimization for cancer patients in the clinic. However, this hypothesis requires further in vitro and in vivo studies. PMID:23314953

Grimm, Martin; Alexander, Dorothea; Munz, Adelheid; Hoffmann, Juergen; Reinert, Siegmar

2013-09-01

316

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

Microsoft Academic Search

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

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

2000-01-01

317

Oral sex and oral cancer in the context of human papillomavirus infection: lay public understanding  

Microsoft Academic Search

Human papillomavirus (HPV) is a risk factor for ano-genital and cervical cancers and has been associated with head and neck\\u000a malignancies in the context of oral sex for the transmission of the virus. However, the level of knowledge that lay people\\u000a have in terms of HPV transmission through oral sex and oral cancer development remains unknown. A pilot sample of

Mario A. BrondaniMario; Mario A. Cruz-Cabrera; Cheryle Colombe

2010-01-01

318

Endoscopic palliation of esophageal malignancy.  

PubMed

Historically, the development and marketing of the neodymium-yttrium-aluminum-garnet (Nd:YAG) laser was associated with the insertion of markedly fewer conventional prostheses for the palliation of malignant dysphagia. Subsequently, the introduction of self-expandable metal stents (SEMS) has, in turn, led to a diminished role not only for laser therapy but also for other ablative modalities, including bipolar cautery, argon plasma coagulation (APC), and the injection of caustics. Two ablative modalities deserve ongoing consideration, but not because they have been proven to be better or more cost-effective than SEMS. These include photodynamic therapy (PDT), because of its potential to ablate large areas of low-grade malignancy, and injection of chemotherapeutic agents or T-lymphocytes sensitized to an individual malignancy. The latter, while theoretically promising, will require considerably more study before widespread clinical application. PMID:12929047

Kozarek, R A

2003-08-01

319

Malignant teratoma (image)  

MedlinePLUS

A malignant teratoma is a type of cancer consisting of cysts that contain one or more of the three ... embryonic germ layers: ectoderm, mesoderm, and endoderm. Because malignant teratomas have usually spread by the time of ...

320

Chemoprevention of oral cancer: Green tea experience.  

PubMed

Oral cancer has a well characterized progression from premalignant oral epithelial changes to invasive cancer, making oral squamous cell carcinoma an optimal disease for chemoprevention interventions prior to malignant transformation. The primary goal of chemoprevention here is to reverse, suppress, or inhibit the progression of premalignant lesions to cancer. Due to the extended duration of oral pathogenesis, its chemoprevention using natural products has been found promising due to their decreased dose and limited toxicity profiles. This review discusses with an emphasis on the clinical trials using green tea extract (GTE) in chemoprevention of oral premalignant lesions along with use of GTE as a chemopreventive agent in various other cancers as well. It is worthwhile to include green tea extract in an oral screening program for evaluating the premalignant lesions comparing the results between the treated and untreated group. Given the wide acceptance of green tea, its benefits may help in effective chemoprevention oral cancer. PMID:24678188

Ramshankar, Vijayalakshmi; Krishnamurthy, Arvind

2014-01-01

321

Why only areca nut chewing cannot cause oral submucous fibrosis?  

PubMed

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

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

2013-07-01

322

Proposed clinical classification for oral submucous fibrosis.  

PubMed

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

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

2012-03-01

323

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

Microsoft Academic Search

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

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

2000-01-01

324

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

PubMed Central

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

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

2012-01-01

325

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

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.

Warner, Margaret [Center for BioSciences, Department of BioSciences and Nutrition, Karolinska Institutet, Stockholm (Sweden) [Center for BioSciences, Department of BioSciences and Nutrition, Karolinska Institutet, Stockholm (Sweden); Center for Nuclear Receptors and Cell Signaling, Department of Biochemistry and Cell Biology, University of Houston, Houston, TX (United States); Gustafsson, Jan-Ake, E-mail: jan-ake.gustafsson@mednut.ki.se [Center for BioSciences, Department of BioSciences and Nutrition, Karolinska Institutet, Stockholm (Sweden) [Center for BioSciences, Department of BioSciences and Nutrition, Karolinska Institutet, Stockholm (Sweden); Center for Nuclear Receptors and Cell Signaling, Department of Biochemistry and Cell Biology, University of Houston, Houston, TX (United States)

2010-05-21

326

Chronic periodontitis and its possible association with oral squamous cell carcinoma - a retrospective case control study  

PubMed Central

Introduction Different inflammatory processes may trigger the development of malignancies. Therefore, the aim of the present study was to evaluate a potential association between radiological determined chronic periodontitis (CPA) and oral squamous cell carcinoma (OSCC). Methods In a retrospective study, OSCC-patients and a control group without malignant tumors were radiographically examined for bone loss. Via telephone survey and questionnaire, general clinical data on the individual oral hygiene and concomitant diseases together with tobacco and alcohol use were assessed and data were compared between the groups. Results 178 OSCC-patients and 123 controls were included. In univariate analysis, a statistically relevant higher mean bone loss was seen in the OSCC group (4.3 mm (SD: 1.8; 95% confidence interval (CI): 4-4.6) vs. 2.9 mm (SD: 0.7; 95% CI: 2.8-3); p?oral inflammation may be beneficial in reducing one potential cause of OSCC. Therefore, further clinical studies on oral neoplasms should consider clinical periodontal parameters as well.

2013-01-01

327

Measurement of 5-fluorouracil in scalp hair: a possible index of patient compliance with oral adjuvant chemotherapy  

Microsoft Academic Search

.  ?Objective:?Little is known about patient compliance with oral adjuvant chemotherapy. It is estimated to be poor especially in Japan,\\u000a where it is still unusual for patients to be directly informed of their diagnosis of malignancy. 5-Fluorouracil (5-FU) was\\u000a measured in hair samples to assess patient exposure to 5-FU, and its potential usefulness is discussed as an index of compliance\\u000a with

T. Uematsu; M. Nakashima; M. Fujii; K. Hamano; M. Yasutomi; S. Kodaira; T. Kato; K. Kotake; H. Oka; T. Masuike

1996-01-01

328

Argyrophilic nucleolar organizer regions in the evaluation of tumour progression in the oral mucosa: correlation with tissue pathology  

Microsoft Academic Search

The present study has analysed the numbers of argyrophilic nucleolar organizer regions (AgNOR) in normal tissues and in premalignant and malignant lesions of the oral mucosa in order to assess their potential as a biological marker for tumour progression. On comparison of AgNOR numbers in different lesions, carcinomas showed the highest number (4.65±0.98) compared to leukoplakias (2.38±0.47) and normal tissues

K. Raveendran Pillai; K. Sujathan; S. Kannan; Elizabeth K. Abraham; Babu Mathew; N. Sreedevi Amma; M. Krishnan Nair; Venugopal P. Menon

1994-01-01

329

Transepithelial Brush Biopsy - Oral CDx(R) - A Noninvasive Method for the Early Detection of Precancerous and Cancerous Lesions  

PubMed Central

Introduction: The Oral CDx® brush biopsy (BB) method is a computer-assisted sample analysis that detects abnormal cells in all cell layers of the epithelium of the oral mucosa. Method: We took 263 oral BBs from 200 patients with potentially malignant disorders. Results: We received 204 negative results and 39 atypical, 7 positive and 13 inadequate results. SBs were taken in 56 cases. Therefore, the sensitivity for the detection of abnormal cells was 90% and the specificity was 44.1%. The positive predictive value accounted for 47.2% and the NPV accounted for 88.2%. Discussion and Conclusion: For the results of sensitivity and specificity of the Oral CDx® BB, there is still space for improvement but they are already high. Additional methods like DNA-image cytometry may enhance the results. But it is a simple and noninvasive method which does not need a special effort either from the patient or from the clinicians.

S., Casparis; J.M., Borm; M.A., Tomic; A., Burkhardt; M.C., Locher

2014-01-01

330

Transepithelial Brush Biopsy - Oral CDx® - A Noninvasive Method for the Early Detection of Precancerous and Cancerous Lesions.  

PubMed

Introduction: The Oral CDx® brush biopsy (BB) method is a computer-assisted sample analysis that detects abnormal cells in all cell layers of the epithelium of the oral mucosa. Method: We took 263 oral BBs from 200 patients with potentially malignant disorders. Results: We received 204 negative results and 39 atypical, 7 positive and 13 inadequate results. SBs were taken in 56 cases. Therefore, the sensitivity for the detection of abnormal cells was 90% and the specificity was 44.1%. The positive predictive value accounted for 47.2% and the NPV accounted for 88.2%. Discussion and Conclusion: For the results of sensitivity and specificity of the Oral CDx® BB, there is still space for improvement but they are already high. Additional methods like DNA-image cytometry may enhance the results. But it is a simple and noninvasive method which does not need a special effort either from the patient or from the clinicians. PMID:24701540

S, Casparis; J M, Borm; M A, Tomic; A, Burkhardt; M C, Locher

2014-02-01

331

The therapeutic potential of a series of orally bioavailable anti-angiogenic microtubule disruptors as therapy for hormone-independent prostate and breast cancers  

PubMed Central

Therapies for hormone-independent prostate and breast cancer are limited, with the effectiveness of the taxanes compromised by toxicity, lack of oral bioavailability and drug resistance. This study aims to identify and characterise new microtubule disruptors, which may have improved efficacy relative to the taxanes in hormone-independent cancer. 2-Methoxy-3-O-sulphamoyl-17?-cyanomethyl-oestra-1,3,5(10)-triene (STX641), 2-methoxy-3-hydroxy-17?-cyanomethyl-oestra-1,3,5(10)-triene (STX640) and 2-methoxyoestradiol-3,17-O,O-bis-sulphamate (STX140) were all potent inhibitors of cell proliferation in a panel of prostate and breast cancer cell lines. STX641 and STX640 significantly inhibited tumour growth in the MDA-MB-231 xenograft model. STX641 inhibited both in vitro and in vivo angiogenesis. Despite good in vivo activity, STX641 was not as potent in vivo as STX140. Therefore, STX140 was evaluated in the prostate hormone-independent PC-3 xenograft model. STX140 had superior efficacy to docetaxel, 2-MeOE2 and bevacizumab. In contrast to vinorelbine, no significant toxicity was observed. Furthermore, STX140 could be dosed daily over a 60-day period leading to tumour regression and complete responses, which were maintained after the cessation of dosing. This study demonstrates that STX641 and STX140 have considerable potential for the treatment of hormone-independent breast and prostate cancer. In contrast to the taxanes, STX140 can be dosed orally, with no toxicity being observed even after prolonged daily dosing.

Newman, S P; Foster, P A; Ho, Y T; Day, J M; Raobaikady, B; Kasprzyk, P G; Leese, M P; Potter, B V L; Reed, M J; Purohit, A

2007-01-01

332

Precursors to Lymphoproliferative Malignancies  

PubMed Central

We review monoclonal B-cell lymphocytosis (MBL) as a precursor to chronic lymphocytic leukemia and monoclonal gammopathy of undetermined significance (MGUS) as a precursor to plasma cell disorders. These conditions are present in the general population and increase with age. These precursors aggregate with lymphoproliferative malignancies in families suggesting shared inheritance. MBL and MGUS may share some of the same risk factors as their related malignancies but data are limited. While these conditions are characterized by enhanced risk for the associated malignancy, the majority of individuals with these conditions do not progress to malignancy. A key focus for current work is to identify markers that predict progression to malignancy.

Goldin, Lynn R.; McMaster, Mary L.; Caporaso, Neil E.

2013-01-01

333

Galectin-7 as a potential predictive marker of chemo-and/or radio-therapy resistance in oral squamous cell carcinoma  

PubMed Central

Treatment of advanced oral squamous cell carcinoma (OSCC) requires the integration of multimodal approaches. The aim of this study was to identify predictors of tumor sensitivity to preoperative radiotherapy/chemotherapy for OSCC in order to allow oncologists to determine optimum therapeutic strategies without the associated adverse effects. Here, the protein expression profiles of formalin-fixed paraffin-embedded (FFPE) tissue samples from 18 OSCC patients, termed learning cases, who received preoperative chemotherapy and/or radiotherapy followed by surgery were analyzed by quantitative proteomics and validated by immunohistochemistry in 68 test cases as well as in the 18 learning cases. We identified galectin-7 as a potential predictive marker of chemotherapy and/or radiotherapy resistance, and the sensitivity and specificity of the galectin-7 prediction score (G7PS) in predicting this resistance was of 96.0% and 39.5%, respectively, in the 68 test cases. The cumulative 5-year disease-specific survival rate was 75.2% in patients with resistant prediction using G7PS and 100% in patients with sensitive prediction. In vitro overexpression of galectin-7 significantly decreased cell viability in OSCC cell line. Therefore, our findings suggest that galectin-7 is a potential predictive marker of chemotherapy and/or radiotherapy resistance in patients with OSCC. Identification of proteins differentially expressed in OSSC samples from patients sensitive or resistant. The samples were processed by LC-MS and analyzed with 2DICAL.

Matsukawa, Sho; Morita, Kei-ichi; Negishi, Ayako; Harada, Hiroyuki; Nakajima, Yusuke; Shimamoto, Hiroaki; Tomioka, Hirofumi; Tanaka, Kae; Ono, Masaya; Yamada, Tesshi; Omura, Ken

2014-01-01

334

Galectin-7 as a potential predictive marker of chemo- and/or radio-therapy resistance in oral squamous cell carcinoma.  

PubMed

Treatment of advanced oral squamous cell carcinoma (OSCC) requires the integration of multimodal approaches. The aim of this study was to identify predictors of tumor sensitivity to preoperative radiotherapy/chemotherapy for OSCC in order to allow oncologists to determine optimum therapeutic strategies without the associated adverse effects. Here, the protein expression profiles of formalin-fixed paraffin-embedded (FFPE) tissue samples from 18 OSCC patients, termed learning cases, who received preoperative chemotherapy and/or radiotherapy followed by surgery were analyzed by quantitative proteomics and validated by immunohistochemistry in 68 test cases as well as in the 18 learning cases. We identified galectin-7 as a potential predictive marker of chemotherapy and/or radiotherapy resistance, and the sensitivity and specificity of the galectin-7 prediction score (G7PS) in predicting this resistance was of 96.0% and 39.5%, respectively, in the 68 test cases. The cumulative 5-year disease-specific survival rate was 75.2% in patients with resistant prediction using G7PS and 100% in patients with sensitive prediction. In vitro overexpression of galectin-7 significantly decreased cell viability in OSCC cell line. Therefore, our findings suggest that galectin-7 is a potential predictive marker of chemotherapy and/or radiotherapy resistance in patients with OSCC. PMID:24515895

Matsukawa, Sho; Morita, Kei-ichi; Negishi, Ayako; Harada, Hiroyuki; Nakajima, Yusuke; Shimamoto, Hiroaki; Tomioka, Hirofumi; Tanaka, Kae; Ono, Masaya; Yamada, Tesshi; Omura, Ken

2014-04-01

335

Intranodal cystic changes: A potential radiological signature/biomarker to assess the HPV (human papillomavirus) status of cases with oropharyngeal malignancies  

PubMed Central

Objective To determine, if lymph node imaging findings can predict human papillomavirus (HPV) positivity in oropharyngeal squamous cell cancers. Methods and Materials Pre-treatment post-contrast Neck CT of 49 patients (male = 35, female = 14; age range = 45–76) diagnosed with oropharyngeal malignancies, and with available HPV data, were retrospectively reviewed. Metastatic lymph nodes were identified based on standardly accepted size and morphologic criteria. Various lymph node parameters were studied, including presence of cystic foci in the metastatic lymph nodes, abnormal lymph nodes showing low attenuation foci, matted lymph nodes and morphologically normal smaller (<1.5cm) lymph nodes. These parameters were then independently correlated with the available HPV status of these patients. Finally, an extended criteria i.e. intranodal cystic changes in cases with morphologically normal small (<1.5cm) lymph nodes, was correlated with HPV status. Sensitivity, specificity, positive and negative predictive values were calculated. Results Of these 49 cases with oropharyngeal cancers, 27 were HPV positive (+ve) and 22 cases were HPV negative (?ve). 8 cases (3 HPV +ve and 5 HPV ?ve) did not have metastatic lymph nodes. Of remaining 41 cases with metastatic abnormal lymph nodes, 26 were HPV +ve and 15 were HPV ?ve. Of these 41 cases with metastatic lymph nodes, 14 had one or more lymph nodes with cystic foci. Ten of these 14 cases i.e. 71.4% were HPV +ve. Resultant sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cystic foci for the presence of HPV status were 38.4%, 73.3%, 71.4% and 40.7% respectively. Intranodal cystic changes in cases with morphologically normal small (<1.5cm) lymph nodes were found in 5 cases; all 5 were HPV positive. Resultant accuracy was specificity and PPV of 100%, sensitivity of 19.2 % and NPV of 41.6 %. Conclusion Intranodal cystic changes seen on the pretreatment post-contrast CT Neck of patients with oropharyngeal malignancies are radiological signatures strongly associated with the HPV status of the patient. The results in this initial study warrant larger prospective studies to determine if this finding may be used in addition to other molecular biomarkers to help identify those patients that may be amenable to the most appropriate treatment options.

Morani, Ajaykumar C; Eisbruch, Avraham; Carey, Thomas E.; Hauff, Samantha J.; Walline, Heather M.; Mukherji, Suresh K

2013-01-01

336

Collecting and Storing Malignant, Borderline Malignant Neoplasms, and Related Samples From Young Patients With Cancer  

ClinicalTrials.gov

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

2014-02-13

337

Oral tolerance.  

PubMed

Multiple mechanisms of tolerance are induced by oral antigen. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral antigen induces T-helper 2 [interleukin (IL)-4/IL-10] and Th3 [transforming growth factor (TGF)-beta] T cells plus CD4+CD25+ regulatory cells and latency-associated peptide+ T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-beta, cholera toxin B subunit, Flt-3 ligand, and anti-CD40 ligand. Oral (and nasal) antigen administration suppresses animal models of autoimmune diseases including experimental autoimmune encephalitis, uveitis, thyroiditis, myasthenia, arthritis, and diabetes in the non-obese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, graft rejection, allergy, colitis, stroke, and models of Alzheimer's disease. Oral tolerance has been tested in human autoimmune diseases including multiple sclerosis (MS), arthritis, uveitis, and diabetes and in allergy, contact sensitivity to dinitrochlorobenzene (DNCB), and nickel allergy. Although positive results have been observed in phase II trials, no effect was observed in phase III trials of CII in rheumatoid arthritis or oral myelin and glatiramer acetate (GA) in MS. Large placebo effects were observed, and new trials of oral GA are underway. Oral insulin has recently been shown to delay onset of diabetes in at-risk populations, and confirmatory trials of oral insulin are being planned. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time, and antigen-specific mechanisms of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy, and early therapy. PMID:16048553

Faria, Ana M C; Weiner, Howard L

2005-08-01

338

Management of malignant hyperthermia: diagnosis and treatment  

PubMed Central

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.

Schneiderbanger, Daniel; Johannsen, Stephan; Roewer, Norbert; Schuster, Frank

2014-01-01

339

Dual role of podoplanin in oral cancer development.  

PubMed

Podoplanin plays a crucial role for normal and pathological tissue development. Known as a lymphatic endothelial marker, podoplanin has been found to be overexpressed in tumor cells of various cancers with a certified involvement in tumor progression, invasion and metastasis. Oral cancer includes a heterogeneous group of malignancies with unpredictable behaviour and sometimes poor prognosis. Based on these facts, development of new molecular markers with a more reliable impact on therapy and prognosis is required. The present study was designed to characterize podoplanin expression in tumor cells of lip, oral cavity, tongue and pharynx squamous cell carcinomas, together with lymphatic vessels distribution, morphology, density and their impact on tumor progression. Evaluation of podoplanin by D2-40 immunohistochemistry assessement on 56 cases of oral cancers, revealed two different expression patterns in tumor cells depending on their location. Peri-tumor and intra-tumor lymphatic vessels density, morphology and distribution were correlated with lymph node status but not with tumor stage. The highest number of lymphatic vessels was observed in grade 3 squamous cell carcinomas. Dual expression of podoplanin in tumor cells and lymphatics with particular patterns correlated with histopathology and lymph node status in oral cancer, representing the molecular basis for testing podoplanin as a potential target for anti D2-40 antibody based therapy. PMID:24815836

Cîrligeriu, Laura; Cimpean, Anca Maria; Raica, Marius; Doro?, Caius Ioan

2014-01-01

340

Diagnostic Potential of miR-126, miR-143, miR-145, and miR-652 in Malignant Pleural Mesothelioma.  

PubMed

Malignant pleural mesothelioma (MPM) is difficult to distinguish from reactive mesothelial proliferations (RMPs). It is uncertain whether miRNAs are useful biomarkers for differentiating MPM from RMPs. Thus, we screened with a quantitative RT-PCR (RT-qPCR)-based platform the expression of 742 miRNAs in formalin-fixed, paraffin-embedded, preoperative diagnostic biopsy samples, surgically resected MPM specimens previously treated with chemotherapy, and corresponding non-neoplastic pleura (NNP), from five patients. miR-126, miR-143, miR-145, and miR-652 were significantly down-regulated (?twofold) in resected MPM and/or chemotherapy-naďve diagnostic tumor biopsy samples. The miRNA expression pattern was validated by RT-qPCR in a cohort of 40 independent MPMs. By performing binary logistic regression on the RT-qPCR data for the four miRNAs, the established four-miRNA classifier differentiated MPM from NNP with high sensitivity and specificity (area under the curve, 0.96; 95% CI, 0.92-1.00). The classifier's optimal logit(P) value of 0.62 separated NNP and MPM samples with a sensitivity of 0.95 (95% CI, 0.89-1.00), a specificity of 0.93 (95% CI, 0.87-0.99), and an overall accuracy of 0.94 (95% CI, 0.88-1.00). The level of miR-126 in MPM was inversely correlated with that of the known target, the large neutral amino acid transporter, small subunit 1 (r = -0.38; 95% CI, -0.63 to -0.06). Overall, these results indicate that these four miRNAs may be suitable biomarkers for distinguishing MPM from RMPs. PMID:24912849

Andersen, Morten; Grauslund, Morten; Ravn, Jesper; Sřrensen, Jens B; Andersen, Claus B; Santoni-Rugiu, Eric

2014-07-01

341

Oral complications in cancer patients  

SciTech Connect

Ionizing radiation used in treating the head and neck area produces oral side effects such as mucositis, salivary changes, trismus and radiation caries. Sequelae of cancer chemotherapy often include oral stomatitis, myelosuppression and immunosuppression. Infections of dental origin in compromised patients are potentially lethal. Specific programs to eliminate dental pathology before radiation and chemotherapy, and to maintain oral hygiene during and after therapy, will minimize these complications.

Carl, W.

1983-02-01

342

Urokinase Plasminogen Activator Receptor (uPAR) and Plasminogen Activator Inhibitor-1 (PAI-1) Are Potential Predictive Biomarkers in Early Stage Oral Squamous Cell Carcinomas (OSCC)  

PubMed Central

Oral squamous cell carcinoma (OSCC) is often associated with metastatic disease and a poor 5 year survival rate. Patients diagnosed with small tumours generally have a more favourable outcome, but some of these small tumours are aggressive and lead to early death. To avoid harmful overtreatment of patients with favourable prognosis, there is a need for predictive biomarkers that can be used for treatment stratification. In this study we assessed the possibility to use components of the plasminogen activator (PA) system as prognostic markers for OSCC outcome and compared this to the commonly used biomarker Ki-67. A tissue-micro-array (TMA) based immunohistochemical analysis of primary tumour tissue obtained from a North Norwegian cohort of 115 patients diagnosed with OSCC was conducted. The expression of the biomarkers was compared with clinicopathological variables and disease specific death. The statistical analyses revealed that low expression of uPAR (p?=?0.031) and PAI-1 (p?=?0.021) in the tumour cells was significantly associated with low disease specific death in patients with small tumours and no lymph node metastasis (T1N0). The commonly used biomarker, Ki-67, was not associated with disease specific death in any of the groups of patients analysed. The conclusion is that uPAR and PAI-1 are potential predictive biomarkers in early stage tumours and that this warrants further studies on a larger cohort of patients.

Hadler-Olsen, Elin; Uhlin-Hansen, Lars; Svineng, Gunbj?rg

2014-01-01

343

Oral leukoplakia.  

PubMed

Leukoplakia has evolved as a clinico-pathologic concept over many years, with the current clinical designation being accepted worldwide. Reflective of the biology of leukoplakia is the concept of cellular atypia and epithelial dysplasia. Adding to a better understanding of leukoplakia in general has been the definition of relevant clinical subsets which, in some cases, includes etiology (snuff), while in other cases a verrucous clinical appearance will suggest a more aggressive anticipated behavior pattern. Tobacco usage, in many of its forms, remains the prime etiologic factor; however, other considerations also apply. More recently, the potential etiologic role of Candida albicans has been stressed, as well as its possible role in carcinogenesis. So-called oral hairy leukoplakia has been defined in relation to a possible Epstein-Barr viral infection, usually in the immunosuppressed patient. Other viruses, human papilloma virus in particular, have been implicated in leukoplakia, while genetic alterations involving tumor suppressor elements (p53) have also been investigated. Finally, the management of this common condition remains a variable and includes local, topical, and systemic therapies such as anti-oxidants, carotenoids, and retinoids. PMID:7548621

Sciubba, J J

1995-01-01

344

Upregulation of miR-31* Is Negatively Associated with Recurrent/Newly Formed Oral Leukoplakia  

PubMed Central

Background Oral leukoplakia (OLK) is a potentially malignant disorder of the oral cavity. However, the underlying mechanism of OLK is still unclear. In this study, we explore possible miRNAs involved in OLK. Methodology/Principal Findings Using miRNA microarrays, we profiled miRNA expression in OLK and malignantly transformed OLK (mtOLK) tissue samples. The upregulation of miR-31*, miR-142-5p, miR-33a, miR-1259, miR-146b-5p, miR-886-3p, miR-886-5p, miR-519d, and miR-301a along with the downregulation of miR-572, miR-611, miR-602, miR-675, miR-585, miR-623, miR-637, and miR-1184 in mtOLK were new observations. Fluorescence in situ hybridization (FISH) analyses confirmed that miR-31* is highly expressed in mtOLK. There was a significant difference between the FISH score (p<0.05) in patients with or without recurrent/newly formed OLK. Functional analyses demonstrated that a miR-31* inhibitor decreased apoptosis in the Leuk-1, which is an immortalized oral epithelial cell line spontaneously derived from an oral leukoplakia lesion. miR-31* regulated apoptosis, cell proliferation, migration, and invasion in the HOIEC, which is a HPV E6/E7-immortalized oral epithelial cell line. Furthermore, miR-31* modulated the biological functions of apoptosis, cell proliferation, cell cycle, migration, and invasion in the oral squamous cell carcinoma cell line, Cal-27. Using bioinformatic analyses and dual luciferase reporter assays, we determined that the 3? untranslated region of fibroblast growth factor 3 (FGF3) is the target of miR-31*. Expression of FGF3 was downregulated or upregulated in the presence of a miR-31* mimic or inhibitor, respectively. Conclusions/Significance Upregulation of miR-31* is negatively associated with recurrent/newly formed OLK. MiR-31* may exert similar but distinguishable effects on biological function in oral cells with different malignant potential. FGF3 is the target of miR-31*. miR-31* may play an important role during OLK progression through regulating FGF3. MiRNA* strands may also have prominent roles in oral carcinogenesis.

Zhang, Chen-Yang; Zhang, Xiao-Yun; Shi, Lin-Jun; Zhou, Zeng-Tong; Jiang, Wei-Wen

2012-01-01

345

Rheumatic Diseases and Malignancies  

PubMed Central

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

BOJINCA, Violeta; JANTA, Iustina

2012-01-01

346

Multiple metastatic tumors in the oral cavity  

PubMed Central

Metastatic lesions to the oral region are uncommon and account for approximately 1% of all malignant oral tumors. In 25% of the cases, oral metastases are found to be the first sign of the metastatic spread; and in 23% of the cases, it is the first indication of an undiscovered malignancy at a distant site. Metastases to oral soft tissues are even less frequent than jaw bones. Because of its rarity, the clinical presentation of a metastatic lesion in the oral cavity can be deceiving, leading to a misdiagnosis of a benign process; therefore, in any case where the clinical presentation is unusual, especially in patients with a known malignant disease, a biopsy is mandatory. Here, we are presenting a rare case of multiple secondary tumors in the attached gingiva in an otherwise apparently healthy patient with no other symptoms of the primary tumor. It subsequently led to the diagnosis of Pancoast tumor (bronchoalveolar carcinoma) metastasizing simultaneously to multiple sites in the oral cavity and bilateral adrenal glands.

Beena, VT; Panda, Swagatika; Heera, R; Rajeev, R

2011-01-01

347

Infections as complications of neuroleptic malignant syndrome.  

PubMed

Neuroleptic malignant syndrome is an uncommon but potentially fatal side effect of antipsychotic drug treatment. Several serious complications have been associated with neuroleptic malignant syndrome, such as acute renal failure, deep venous thrombosis, pulmonary embolism and aspiration pneumonia. Reports on infections other than aspiration pneumonia appear, from the literature, to be uncommon. Four cases of infection (three cases of upper respiratory tract infection and one case of urinary tract infection) which developed during the course of neuroleptic malignant syndrome are reported and pathophysiological mechanisms underlying their presentation are suggested. PMID:18609425

Bilanakis, Nikolaos; Peritogiannis, Vaios; Kalampokis, Georgios

2009-01-01

348

Paraneoplastic dermatological manifestation of gastrointestinal malignancies  

PubMed Central

Numerous dermatological disorders have been associated with underlining malignancies of the gastrointestinal (GI) tract. Such cutaneous manifestations might have an important diagnostic value if they are the sole expressions of otherwise asymptomatic carcinomas. The recognition of some typical paraneoplastic dermatologic disorders can lead to the prompt diagnosis of the underlying malignancy, timely administration of therapy, and ultimately, better prognosis. In this review we discuss the most common paraneoplastic dermatological syndromes from the perspective of the practicing gastroenterologist. We also outline a comprehensive practical approach for the evaluation for occult malignancy in patients presenting with cutaneous findings potentially associated with GI cancers.

Dourmishev, Lyubomir A; Draganov, Peter V

2009-01-01

349

Oral proliferative verrucous leukoplakia treated with the photodynamic therapy: a case report  

PubMed Central

Summary Aims About 60% of the oral cancer arise on a pre-existent potentially malignant disorder of oral mucosa like the oral proliferative verrucous leukoplakia. The treatment with the photodynamic therapy of these lesions represents, in the last years, an innovative, non-invasive and effective therapeutic possibility to achieve the secondary prevention of oral cancer. In the last decade, case reports have described patients with similar treated through a photochemical reaction induced by laser light. The aim of this study is to evaluate the effectiveness of the topical 5-ALA photodynamic therapy in the treatment of a case of Oral proliferative verrucous leukoplakia. Case report A female patient of 80 years old affected by white verrucous plaques on the right buccal mucosa was recruited for our case report. The right side lesion was treated with the photodynamic therapy with topical administered 5-aminolevulinic acid using the 635 nm laser light to activate the photosensitizer. Results The lesion showed complete response after 4 sessions of photodynamic therapy and no recurrence was noticed after 12 months. Conclusions The photodynamic therapy can be considered an effective treatment in the management of oral verrucous proliferative leukoplakia, but more clinical trials, with prolonged follow-up controls, are necessary to evaluate its effectiveness in the mid and long time period.

Romeo, Umberto; Russo, Nicola; Palaia, Gaspare; Tenore, Gianluca; Del Vecchio, Alessandro

2014-01-01

350

[Cancers of the oral and genital mucosa].  

PubMed

Squamous cell carcinomas account for over 90 % of cancers of the oral cavity in France. Alcohol and tobacco are the main risk factors. Delay in diagnosis is unfortunately frequent. The management of the cancer is based on surgery, possibly associated to radiation therapy and chemotherapy. The survival rate at 5 years does not exceed 30-40%. We hope to see a decrease in the number of oral cancer thanks to the development of preventive medicine (alcohol and tobacco cessation and early detection of potentially malignant lesions). Vulvar squamous cell carcinoma is a rare disease which traditionally affect elderly woman but continues to rise in incidence especially in younger women. There are at least 2 forms of genital squamous cell carcinoma. The most common form is found on older women arising in a background of lichen sclerosus and the second is associated with "high risk" human papillomavirus infection affecting younger women. A biopsy is usually required for diagnosis. Attempts to reduce genital cancer must focus on treating precursor lesions, namely lichen sclerosus and HPV-related intraepithelial neoplasia (VIN and PIN). Most genital cancer occur on undiagnosed or untreated lichens sclerosus, vulvar inspection when women attend for their cervical smears or seeking about significance of any chronic genital symptom by a clinical examination. PMID:24167879

Dehen, Laure; Schwob, Emilie; Pascal, Francis

2013-09-01

351

Salivary Total Antioxidant Capacity and Lipid Peroxidation in Patients with Erosive Oral Lichen Planus  

PubMed Central

Background and aims. Oral lichen planus is a common chronic inflammatory disease of the oral mucosa with malignant potential, pathogenesis of which is not still well known. Free radicals and reactive oxygen species can play an important role in the pathogenesis of oral lichen planus. The aim of this study was to investigate salivary oxidative stress and antioxidant systems in patients with oral lichen planus. Materials and methods.In this case-control study, 30 patients with oral lichen planus (case group) and 30 age-and gender-matched healthy subjects (control group), referring to Dental School of Babol University of Medical Sciences, were selected using simple sampling method. Unstimulated saliva of the two groups was collected. Salivary total antioxidant capacity (TAC) and lipid peroxidation products were investigated and compared, using ferric reducing antioxidant power (FRAP) and thiobarbituric acid reactive substance (TBARS) methods, respectively. Data were analyzed using Student' t-test. Results. The mean and standard deviation of salivary TAC in patients with oral lichen planus (297.23 ± 149.72 ?M) was significantly lower than that in the controls (791.43 ± 183.95 ?M; P & 0.0001), and mean and standard deviation of salivary malondialdehyde (MDA) (0.49 ± 0.30 ?M) was remarkably higher in oral lichen planus patients compared to the control group (0.15 ± 0.11 ?M) (P & 0.0001). TAC was also reduced in both groups in line with an increase in the level of MDA (P & 0.0001, r = -0.48). Conclusion. The results of this study suggested that an increase in oxidative stress and an imbalance in antioxidant defense system in the saliva of oral lichen planus patients may be involved in the pathogenesis of oral lichen planus.

Shirzad, Atena; Pouramir, Mahdi; Seyedmajidi, Maryam; Jenabian, Niloofar; Bijani, Ali; Motallebnejad, Mina

2014-01-01

352

Oral and systemic photoprotection.  

PubMed

Photoprotection can be provided not only by ultraviolet (UV) blockers but also by oral substances. Epidemiologically identified associations between foods and skin cancer and interventional experiments have discovered mechanisms of UV skin damage. These approaches have identified oral substances that are photoprotective in humans. UV inhibits adenosine triphosphate (ATP) production causing an energy crisis, which prevents optimal skin immunity and DNA repair. Enhancing ATP production with oral nicotinamide protects from UV immunosuppression, enhances DNA repair and reduces skin cancer in humans. Reactive oxygen species also contribute to photodamage. Nontoxic substances consumed in the diet, or available as oral supplements, can protect the skin by multiple potential mechanisms. These substances include polyphenols in fruit, vegetables, wine, tea and caffeine-containing foods. UV-induced prostaglandin E2 (PGE2 ) contributes to photodamage. Nonsteroidal anti-inflammatory drugs and food substances reduce production of this lipid mediator. Fish oils are photoprotective, at least partially by reducing PGE2 . Orally consumed substances, either in the diet or as supplements, can influence cutaneous responses to UV. A current research goal is to develop an oral supplement that could be used in conjunction with other sun protective strategies in order to provide improved protection from sunlight. PMID:24313740

Chen, Andrew C; Damian, Diona L; Halliday, Gary M

2014-01-01

353

Therapeutic potential of oral tolerance  

Microsoft Academic Search

The immune system has the daunting task of distinguishing between self and non-self. The mucosal immune system, present along the respiratory, gastrointestinal and genitourinary tracts, has the additional burden of coexisting with an abundance of dietary antigens and lumenal bacterial flora. A key feature of the mucosal immune system is its ability to remain tolerant to these antigens while retaining

Ling Shao; Lloyd Mayer

2004-01-01

354

Chitosan microparticles for oral vaccination  

Microsoft Academic Search

Although oral vaccination has numerous advantages over parenteral injection, degradation of the vaccine in the gut and low uptake in the lymphoid tissue of the gastrointestinal tract still complicate the development of oral vaccines. In this study chitosan microparticles were prepared and characterized with respect to size, zeta potential, morphology and ovalbumin-loading and -release. Furthermore, the in vivo uptake of

I. M van der Lubben; J. C Verhoef; A. C van Aelst; G Borchard; H. E Junginger

2001-01-01

355

Epigenetic lesions in malignant melanoma.  

PubMed

Malignant melanoma arises through a series of genetic and epigenetic events. A more profound understanding of the biology of metastatic melanoma should greatly aid in the development of new and effective treatments. Currently, avenues being pursued to improve treatment of metastatic melanoma include dendritic cell vaccines and other vaccination strategies, tyrosine kinase inhibitors, adoptive transfer of ex vivo stimulated T cells, and, as reviewed here, epigenetic approaches. The "methylator phenotype", with inactivation by promoter hypermethylation of numerous genes in malignant melanoma cell lines and primary tumors (p16, PTEN, RASSF1, estrogen receptor, retinoic acid receptor beta, SOCS1 and -2, MGMT etc.) offers a strong rationale for treatment approaches based on the use of DNA demethylating agents. The clinical literature on treatment of metastasized malignant melanoma with either 5-azacytidine or 5-aza-2'-deoxycytidine (decitabine) is reviewed. Future trials in malignant melanoma with these compounds might profit from prolonged low-dose exposure, since they unfold their full effects not immediately but with a certain delay, which may be associated with their DNA demethylating activity. Combinations of DNA demethylation agents with either histone deacetylase inhibitors, interleukin-2, chemotherapy or tamoxifen have been embarked on both in in vitro models of melanoma and recent clinical trials. The in vitro synergism between inhibitors of DNA methylation and histone deacetylation strongly invites a systematic study of combinations of both groups of agents. Up-regulation of cancer testis antigens by epigenetic therapy in melanoma also offers a very strong rationale to place these drugs and schedules within a larger treatment concept of immunotherapy which may include also T cell activation e.g. by interleukin-2, and vaccination strategies. In conclusion, the epigenome of malignant melanoma, with a well-established in vitro reversal potential, holds promise as a novel molecular target. PMID:18289047

Schwabe, M; Lübbert, M

2007-12-01

356

Malignant mesothelioma: attributable risk of asbestos exposure  

Microsoft Academic Search

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

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

1994-01-01

357

AIDS-Related Malignancies  

Microsoft Academic Search

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

G. MICHAEL WOOL

358

Acquisition of lymph node, but not distant metastatic potentials, by the overexpression of CXCR4 in human oral squamous cell carcinoma  

Microsoft Academic Search

Recently, it has been suggested that chemokine\\/receptor interactions determine the destination of the invasive tumor cells in several types of cancer. It has also been proposed that the stromal cell-derived factor-1 (SDF-1; CXCL12)\\/CXCR4 system might be involved lymph node metastasis in oral squamous cell carcinoma (SCC). In order to further clarify the role of the SDF-1\\/CXCR4 system in oral SCC,

Daisuke Uchida; Nasima-Mila Begum; Yoshifumi Tomizuka; Takashi Bando; Ammar Almofti; Hideo Yoshida; Mitsunobu Sato

2004-01-01

359

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

PubMed

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

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

2009-10-01

360

Oral feeding.  

PubMed

Early nutrition can help to improve energy and protein intake and decrease the negative impact of the metabolic response to surgery. A key goal is to identify patients who exhibit increased respiration risk before beginning oral alimentation. Once a simple bedside 3-oz (90 ml) challenge, or early intervention in the oral care, administered by a trained provider is passed, specific diet recommendations can be made safely and confidently without the need for further objective dysphagia testing. Gastrointestinal motility disorders occur as part of the pathophysiology of diseases and critical illness, or are a result of medication therapies or enteral feeding complications. Inadequate energy intake in the first 7 days following extubation have recently been described. It would be highly beneficial to determine when it is best to initiate timely oral alimentation for recovering extubated intensive care unit (ICU) and more specifically surgical ICU patients to support the maintenance and rebuilding of lean body mass, maintain hydration, and permit the ingestion of oral medications. In a cross-sectional multicenter study conducted in 18 Spanish ICUs, within the scope of the 2007 European Nutrition Day, only 95 of 348 investigated patients (27.3%) received oral nutritional support. Constipation and diarrhea were common adverse effects. Unexpectedly, however, constipation episodes were more frequent than diarrhea in the patients not receiving oral nutritional support. PMID:23075585

Alvárez-Falcón, Ana; Ruiz-Santana, Sergio

2013-01-01

361

Myofibroblasts in oral lesions: A review.  

PubMed

Myofibroblasts (MFs) are modified fibroblasts that express features of smooth muscle differentiation and were first observed in granulation tissue during wound healing. These cells play a key role in physiologic and pathologic processes like wound healing and tumorigenesis. The presence of MFs has been reported in normal oral tissues and pathologic conditions like reactive lesions, benign tumors, locally aggressive tumors and malignancies affecting the oral cavity. This article briefly reviews the important hallmarks related to the discovery, characterization and tissue distribution of MFs in oral health and disease. PMID:24959038

Pinisetti, Soujanya; Manyam, Ravikanth; Suresh, Babburi; Aparna, V

2014-01-01

362

Myofibroblasts in oral lesions: A review  

PubMed Central

Myofibroblasts (MFs) are modified fibroblasts that express features of smooth muscle differentiation and were first observed in granulation tissue during wound healing. These cells play a key role in physiologic and pathologic processes like wound healing and tumorigenesis. The presence of MFs has been reported in normal oral tissues and pathologic conditions like reactive lesions, benign tumors, locally aggressive tumors and malignancies affecting the oral cavity. This article briefly reviews the important hallmarks related to the discovery, characterization and tissue distribution of MFs in oral health and disease.

Pinisetti, Soujanya; Manyam, Ravikanth; Suresh, Babburi; Aparna, V

2014-01-01

363

Venous thromboembolism in malignant gliomas  

PubMed Central

Summary Malignant gliomas are associated with a very high risk of venous thromboembolism (VTE). While many clinical risk factors have previously been described in brain tumor patients, the risk of VTE associated with newer anti-angiogenic therapies such as bevacizumab in these patients remains unclear. When VTE occurs in this patient population, concern regarding the potential for intracranial hemorrhage complicates management decisions regarding anticoagulation, and these patients have a worse prognosis than their VTE-free counterparts. Risk stratification models identifying patients at high risk of developing VTE along with predictive plasma biomarkers may guide the selection of eligible patients for primary prevention with pharmacologic thromboprophylaxis. Recent studies exploring disordered coagulation, such as increased expression of tissue factor (TF), and tumorigenic molecular signaling may help to explain the increased risk of VTE in patients with malignant gliomas.

JENKINS, E. O.; SCHIFF, D.; MACKMAN, N.; KEY, N. S.

2010-01-01

364

Contemporary management of cancer of the oral cavity  

PubMed Central

Oral cancer represents a common entity comprising a third of all head and neck malignant tumors. The options for curative treatment of oral cavity cancer have not changed significantly in the last three decades; however, the work up, the approach to surveillance, and the options for reconstruction have evolved significantly. Because of the profound functional and cosmetic importance of the oral cavity, management of oral cavity cancers requires a thorough understanding of disease progression, approaches to management and options for reconstruction. The purpose of this review is to discuss the most current management options for oral cavity cancers.

Genden, Eric M.; Silver, Carl E.; Takes, Robert P.; Suarez, Carlos; Owen, Randall P.; Haigentz, Missak; Stoeckli, Sandro J.; Shaha, Ashok R.; Rapidis, Alexander D.; Rodrigo, Juan Pablo; Rinaldo, Alessandra

2010-01-01

365

Oral verrucous hyperplasia: a case report.  

PubMed

Oral verrucous hyperplasia is a whitish or pinkinsh elevated pre malignant lesion which occurs rarely. Its is also considered to be an early form of verrucous carcinoma. We have reported a case of verrucous hyperplasia which was diagnosed and treated with buccal fat pad as graft. PMID:25018612

Navaneetham, Anuradha; Dayanand Saraswathi, M C; Santosh, B S

2014-09-01

366

Proteomic analysis of malignant B-cell derived microparticles reveals CD148 as a potentially useful antigenic biomarker for mantle cell lymphoma diagnosis.  

PubMed

The diagnosis of mature B-cell neoplasms (MBCN) remains difficult in a number of cases, especially leukemic phases of non-Hodgkin lymphoma, for which discriminating criteria or biomarker are often lacking. To identify new surface biomarkers, we developed an original proteomic approach based on mass spectrometry analysis of plasma membrane microparticles derived from chronic B-cell lymphoproliferations of single patients: chronic lymphocytic leukemia (CLL), small cell lymphoma (SLL) and mantle cell lymphoma (MCL). A straightforward selection process for proteomic-based candidate biomarker identification was further constructed in order to propose potentially useful and relevant biomarkers. Comparison of the lists of the proteins identified in each pathology combined to highly stringent MS validation criteria for protein identification allowed to propose CD148, a membrane receptor with phosphatase activity, as a discriminating biomarker candidate. Flow cytometry analyses, performed on 158 patients and 30 controls, showed that an anti-CD148 antibody stained significantly higher MCL than CLL and SLL circulating cells (p<0.0001), which validates CD148 overexpression in MCL. Our results indicate that a medium or high CD148 expression level may exclude the diagnosis of CLL and high CD148 expression levels (CD148 MFI equal or superior to 2 times the value obtained with CLL/SLL) allows MCL diagnosis to be suspected with 91% specificity (versus CLL and SLL) and 78% sensitivity. This study is one of the first where proteomic strategies allowed to identify a potentially useful biomarker. PMID:19413345

Miguet, Laurent; Béchade, Guillaume; Fornecker, Luc; Zink, Estelle; Felden, Claire; Gervais, Carine; Herbrecht, Raoul; Van Dorsselaer, Alain; van Dorsselaer, Alain; Mauvieux, Laurent; Sanglier-Cianferani, Sarah

2009-07-01

367

Galectins in hematological malignancies  

PubMed Central

Carbohydrates are traditionally considered to be an important source of energy for living organisms. In the field of biology, they are defined as organic compounds composed of carbon, hydrogen, and oxygen that are organized into ring structures. The analysis of these structures and their functions has led to a new field of biology called “glycobiology.” In the biomedical sciences, glycobiology is rapidly emerging to be an integral part of complex biological processes. Changes in glycan structures and the interactions of these structures with endogenous carbohydrate-binding proteins, known as lectins, are now considered to be potential biomarkers on cancer cells for monitoring tumor progression. Evidence suggesting that the interactions between lectins and their ligands have a major role in the different steps of cancer progression has accumulated at a rapid pace and has gained the attention of several oncologists. This is particularly true for galectin family members because changes in their expression levels correlate with alterations in cancer cell growth, apoptosis, and cell-cell and cell-matrix interactions. Here we provide an integrated view of the role of galectins in hematological malignancies.

St-Pierre, Yves

2011-01-01

368

Tubulin ?-6 chain is a stably expressed reference gene in archival samples of normal oral tissue and oral squamous cell carcinoma.  

PubMed

One of the most critical factors in gene expression studies using quantitative real-time PCR is the choice of reference gene. Many of the commonly used reference genes have been shown to vary during a number of biological processes as well as between tissues. It is therefore important to always verify the stability of the gene of choice for all new tissues and experimental conditions. Here, we used two publicly available computer software packages (GeNorm and NormFinder) to investigate the stability of eight potential reference genes in formalin-fixed paraffin-embedded (FFPE) samples from normal oral tissue of different origin as well as from oral squamous cell carcinomas. Both programs found the tubulin ?-6 chain (TUBA6) and ribosomal protein S13 (RPS13) to have the most stable expression between malignant and non-malignant tissue. NormFinder also found TUBA6 to be the most stable gene when samples were grouped according to tissue origin. FFPE samples constitute a large research resource, which considerably increases the number of samples available for analysis, leading to more reliable conclusions. Verification of a proper reference gene in oral FFPE tissue is therefore of great importance for future studies. PMID:22993556

Rentoft, Matilda; Hultin, Sara; Coates, Philip John; Laurell, Göran; Nylander, Karin

2010-05-01

369

Tubulin ?-6 chain is a stably expressed reference gene in archival samples of normal oral tissue and oral squamous cell carcinoma  

PubMed Central

One of the most critical factors in gene expression studies using quantitative real-time PCR is the choice of reference gene. Many of the commonly used reference genes have been shown to vary during a number of biological processes as well as between tissues. It is therefore important to always verify the stability of the gene of choice for all new tissues and experimental conditions. Here, we used two publicly available computer software packages (GeNorm and NormFinder) to investigate the stability of eight potential reference genes in formalin-fixed paraffin-embedded (FFPE) samples from normal oral tissue of different origin as well as from oral squamous cell carcinomas. Both programs found the tubulin ?-6 chain (TUBA6) and ribosomal protein S13 (RPS13) to have the most stable expression between malignant and non-malignant tissue. NormFinder also found TUBA6 to be the most stable gene when samples were grouped according to tissue origin. FFPE samples constitute a large research resource, which considerably increases the number of samples available for analysis, leading to more reliable conclusions. Verification of a proper reference gene in oral FFPE tissue is therefore of great importance for future studies.

RENTOFT, MATILDA; HULTIN, SARA; COATES, PHILIP JOHN; LAURELL, GORAN; NYLANDER, KARIN

2010-01-01

370

Cyclooxygenase-2 Gene Polymorphisms Reduce Risk of Oral Premalignant Lesions  

PubMed Central

Oral premalignant lesions (OPLs) have the potential to transform into malignant oral cancers. The overexpression of cyclooxygenase-2 (COX-2) gene is frequently found in OPLs and oral cancers, suggesting that this gene may play an important role in the progression of oral cancer. Single nucleotide polymorphisms (SNPs) of COX-2 gene have been associated with the risk of multiple cancers, but their effects on OPL susceptibility have not been sufficiently evaluated. Here we conducted a case-control study including 147 patients with OPL and 147 healthy matched controls. We evaluated the effects of three potentially functional COX-2 polymorphisms, including ?765G>C (rs20417), exon10+837T>C (rs5275), and exon10?90C>T (rs689470), on OPL risk. We found that the variant-containing genotypes of COX-2 exon10+837T>C variant were associated with a significantly reduced OPL risk with an odds ratio (OR) of 0.48 (95% CI, 0.28?0.80). This protective effect was also significant in males, younger subjects, ever smokers, and ever drinkers. Consistently, a common haplotype (WMW, in the order of ?765G>C, exon10+837T>C, and exon10?90C>T; W, wild-type allele, M, variant allele) and a common diplotype (WWW/WMW) that contained the variant allele of exon10+837T>C were both associated with a reduced OPL risk, having ORs of 0.55 (95% CI, 0.33?0.93) and 0.44 (95% CI, 0.22?0.89), respectively. In addition, using never smokers with the variant-containing genotypes as the reference group, we observed an interaction effects between specific COX-2 variants and tobacco smoking in the modulation of OPL risk. Overall, our results provided the first epidemiological evidence indicating that potentially functional polymorphisms of the COX-2 gene may impact OPL susceptibility.

Pu, Xia; Lippman, Scott M.; Yang, Hushan; Lee, J. Jack; Wu, Xifeng

2009-01-01

371

Malignant eroticized countertransference.  

PubMed

Gabbard (1994) divided the pathology of therapists, both male and female, who commit sexual boundary violations into those who are psychotic, those who are predatory psychopaths, those engaging in masochistic surrender, and those called "the lovesick therapist." Lovesick therapists are the most common type and manifest crucial narcissistic themes of "a desperate need for validation by their patients, a hunger to be loved and idealized, and a tendency to use patients to regulate their own self-esteem" (p. 127). Among the psychodynamic aspects of this curiously circumscribed area of loss of reality testing that makes it difficult for the therapist to see how self-destructive and harmful such enactment is, are an unconscious reenactment of incestuous longings, a misperception of the patient's wish for maternal nurturance as a sexual overture, enactments of rescue fantasies, a projected idealization of the self of the therapist, a confusion of the therapist's needs with the patient's needs, a fantasy that love is curative, acting out disavowed rage at the patient, or rage at an organization, an institute, or one's training analyst, a manic defense against mourning, a narcissistic fantasy that their sexual affair is an exception, insecurity regarding masculine identity, and assorted primitive preoedipal themes. Gabbard's (1991) erotized countertransference is one variety of what I have termed malignant eroticized countertransference. His variety is a development that occurs under the pressure of the patient's preemptive and compelling expressions of lust and love, the patient's erotic transference. But malignant eroticized countertransference can also occur without the patient having offered any such expressions; it can even occur on first meeting the patient when he or she walks into the office! This is akin to the romantic "love-at-first-sight" theme so favored in the movies and by novelists, but it is always pathological when it occurs in the therapeutic situation. Countertransference enactments are a creation between the patient and the therapist on a continuum from one pole, where the patient has just walked into the office and contributes almost nothing directly, to the other pole, where the therapist loses control of himself or herself as a response to the unbearable pressure of the patient's lust. In the treatment of malignant eroticized countertransference it seems clear from this discussion that every case should be evaluated psychodynamically and the treatment should be made to fit the patient, not the patient to the treatment. Each situation should be studied in psychodynamic depth without preconceptions based on generalizations or formulas. Therapists who are psychotic should of course be treated with antipsychotic drugs and usually should not be allowed to practice any further. Therapists who are psychopathic or sociopathic predators should certainly never be allowed to practice. Some of the individuals who are "lovesick," or, as I put it "love/lust obsessed," or those who have made a masochistic surrender to a sadistic destructive patient, are in need of reanalysis and have the potential to continue as effective therapists under careful supervision. Therapists like this do not deserve to be summarily dismissed from the profession but, like therapists who develop other serious neurotic problems, should receive appropriate help from us. PMID:9395991

Chessick, R D

1997-01-01

372

Dynamic infrared imaging for the detection of malignancy  

NASA Astrophysics Data System (ADS)

The potential for malignancy detection using dynamic infrared imaging (DIRI) has been investigated in an animal model of human malignancy. Malignancy was apparent in images formed at the vasomotor and cardiogenic frequencies of tumour bearing mice. The observation of malignancy was removed by the administration of an agent that blocks vasodilation caused by nitric oxide (NO). Image patterns similar to those that characterize malignancy could be mimicked in normal mice using an NO producing agent. Apparently DIRI allows for cancer detection in this model through vasodilation caused by malignancy generated NO. Dynamic infrared detection of vasomotor and cardiogenic surface perfusion was validated in human subjects by a comparison with laser Doppler flowmetry (LDF). Dynamic infrared imaging technology was then applied to breast cancer detection. It is shown that dynamic infrared images formed at the vasomotor and cardiogenic frequencies of the normal and malignant breast have image pattern differences, which may allow for breast cancer detection.

Button, Terry M.; Li, Haifang; Fisher, Paul; Rosenblatt, Ruth; Dulaimy, Khaldoon; Li, Song; O'Hea, Brian; Salvitti, Mathew; Geronimo, Veronica; Geronimo, Christine; Jambawalikar, Sachin; Carvelli, Paola; Weiss, Richard

2004-07-01

373

HPV DNA and survivin expression in epithelial oral carcinogenesis: a relationship?  

Microsoft Academic Search

HPV has been thought to be involved in the development of several oral diseases, such as premalignant mucosal lesions and oral carcinoma. Survivin is a recently characterized IAP protein, which is abundantly expressed in most solid and haematological malignancies, but undetectable in normal adult tissues. Aim of this study was to investigate survivin expression and HPV presence in oral premalignant

Lorenzo Lo Muzio; Giuseppina Campisi; Lucia Giovannelli; Pietro Ammatuna; Immacolata Greco; Stefania Staibano; Giuseppe Pannone; Gaetano De Rosa; Chiara Di Liberto; Matteo D'Angelo

2004-01-01

374

Oral cysticercosis: a clinical dilemma.  

PubMed

Cysticercosis is a potentially fatal parasitic disease caused by cysticercus cellulosae, the larval stage of Taenia solium. Oral cysticercosis is a rare entity and represents difficulty in clinical diagnosis. This article reports two cases of oral cysticercosis involving buccal and labial mucosa. Both the cases presented with solitary, nodular swelling that had been clinically diagnosed as a mucocele. Histopathology of excisional biopsy revealed it to be cysticercosis. Single, cystic nodular swelling of oral cavity may be the only evidence of cysticercosis and may present first to dentist. These cases emphasise the role of dentist and thorough histopathological examination in the early diagnosis of disease that can prevent potential systemic complication. PMID:23580668

Wanjari, Sangeeta Panjab; Patidar, Kalpana A; Parwani, Rajkumar N; Tekade, Satyajitraje A

2013-01-01

375

c-fos and c-jun overexpression in malignant cells reduces their tumorigenic and metastatic potential, and affects their MHC class I gene expression.  

PubMed

Reduced co-expression of the c-fos and c-jun protooncogenes has been correlated with the down regulation of H-2K class I major histocompatibility antigens in high-metastatic cell lines from the Lewis lung carcinoma, B16 melanoma and the K1735 melanoma. Transfection of c-jun and c-fos genes into the high metastatic clones D122 (3LL) and F10.9 (B16 melanoma) resulted in activation of H-2 class I gene expression. D122 transfectants expressing high levels of c-jun and c-fos and F10.9 transfectants expressing high levels of c-fos exhibited markedly reduced tumorigenicity and were of low metastatic potential. In contrast, transfection of junB into the low metastatic, high H-2Kb, Db expressor clone A9 (3LL), reduced MHC class I gene expression, and converted the parental low, into high-metastatic cells. The data demonstrate the involvement of genes from the fos and jun family in regulation of MHC class I expression and consequently in regulation of immunogenicity and metastatic competence of tumor cells. PMID:8134110

Yamit-Hezi, A; Plaksin, D; Eisenbach, L

1994-04-01

376

New Potential Therapeutic Approach for the Treatment of B-Cell Malignancies Using Chlorambucil/Hydroxychloroquine-Loaded Anti-CD20 Nanoparticles  

PubMed Central

Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders.

Mezzaroba, Nelly; Zorzet, Sonia; Secco, Erika; Biffi, Stefania; Tripodo, Claudio; Calvaruso, Marco; Mendoza-Maldonado, Ramiro; Capolla, Sara; Granzotto, Marilena; Spretz, Ruben; Larsen, Gustavo; Noriega, Sandra; Lucafo, Marianna; Mansilla, Eduardo; Garrovo, Chiara; Marin, Gustavo H.; Baj, Gabriele; Gattei, Valter; Pozzato, Gabriele; Nunez, Luis; Macor, Paolo

2013-01-01

377

A comprehensive review of oral cancer.  

PubMed

Oral squamous cell carcinomas comprise 2-3% of all new malignancies diagnosed in the United States, making it the 10th most common malignancy. However, for the last few decades, the average five-year survival rate of 50% has not changed significantly. This article reviews the risk factors associated with the development of oral cancer and how premalignant (leukoplakia and erythroplakia) and actual cancerous lesions may appear. Diagnostic tools and aids to diagnosis are discussed, as are treatment modalities. It is imperative that all dental professionals perform a simple head and neck examination in addition to an oral examination during each new patient visit and each six-month recall appointment. Early detection saves lives. PMID:12004680

Casiglia, J; Woo, S B

2001-01-01

378

Advances in Bio-Optical Imaging for the Diagnosis of Early Oral Cancer  

PubMed Central

Oral cancer is among the most common malignancies worldwide, therefore early detection and treatment is imperative. The 5-year survival rate has remained at a dismal 50% for the past several decades. The main reason for the poor survival rate is the fact that most of the oral cancers, despite the general accessibility of the oral cavity, are not diagnosed until the advanced stage. Early detection of the oral tumors and its precursor lesions may be the most effective means to improve clinical outcome and cure most patients. One of the emerging technologies is the use of non-invasive in vivo tissue imaging to capture the molecular changes at high-resolution to improve the detection capability of early stage disease. This review will discuss the use of optical