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1

Oral potentially malignant disorders: Is malignant transformation predictable and preventable?  

PubMed Central

Leukoplakia is the most common potentially malignant disorder of the oral mucosa. The prevalence is approximately 1% while the annual malignant transformation ranges from 2% to 3%. At present, there are no reliable clinicopathological or molecular predicting factors of malignant transformation that can be used in an individual patient and such event can not truly be prevented. Furthermore, follow-up programs are of questionable value in this respect. Cessation of smoking habits may result in regression or even disappearance of the leukoplakia and will diminish the risk of cancer development either at the site of the leukoplakia or elsewhere in the mouth or the upper aerodigestive tract. The debate on the allegedly potentially malignant character of oral lichen planus is going on already for several decades. At present, there is a tendency to accept its potentially malignant behaviour, the annual malignant transformation rate amounting less than 0.5%. As in leukoplakia, there are no reliable predicting factors of malignant transformation that can be used in an individual patient and such event can not truly be prevented either. Follow-up visits, e.g twice a year, may be of some value. It is probably beyond the scope of most dentists to manage patients with these lesions in their own office. Timely referral to a specialist seems most appropriate, indeed. Key words:Oral potentially malignant disorders, oral leukoplakia, oral lichen planus. PMID:24905952

van der Waal, Isaäc

2014-01-01

2

Advances in optical adjunctive AIDS for visualisation and detection of oral malignant and potentially malignant lesions.  

PubMed

Traditional methods of screening for oral potentially malignant disorders and oral malignancies involve a conventional oral examination with digital palpation. Evidence indicates that conventional examination is a poor discriminator of oral mucosal lesions. A number of optical aids have been developed to assist the clinician to detect oral mucosal abnormalities and to differentiate benign lesions from sinister pathology. This paper discusses advances in optical technologies designed for the detection of oral mucosal abnormalities. The literature regarding such devices, VELscope and Identafi, is critically analysed, and the novel use of Narrow Band Imaging within the oral cavity is also discussed. Optical aids are effective in assisting with the detection of oral mucosal abnormalities; however, further research is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant and malignant lesions. PMID:24078812

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

2013-01-01

3

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. PMID:24078812

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

2013-01-01

4

Stromal myofibroblasts in potentially malignant and malignant lesions of the oral cavity  

PubMed Central

Previous studies have demonstrated that myofibroblasts in the adjacent stroma are involved in the development and progression of malignant tumors. The aim of this study was to investigate the involvement of myofibroblasts in the progression of oral squamous cell carcinomas (OSCCs) by determining myofibroblast density in potentially malignant and malignant oral lesions. A total of 69 potentially malignant oral lesions (leukoplakias with mild, moderate or severe dysplasia), 90 OSCCs (well-, moderately and poorly differentiated), eight oral verrucous carcinomas and 29 fibrous hyperplasias were examined for the presence of myofibroblasts using immunohistochemical detection of isoform ? of smooth muscle actin. Myofibroblasts were not identified in the adjacent stroma of fibrous hyperplasias and potentially malignant oral lesions, whereas 59.8% of the oral carcinomas exhibited myofibroblasts in various densities. The density was significantly higher in moderately and poorly differentiated OSCCs when compared with well-differentiated tumors (P=0.04 and P=0.007, respectively). In verrucous carcinomas, the specific variant of well-differentiated OSCC, stromal myofibroblasts were not detected. The results of the present study demonstrated that immunodetection of myofibroblasts does not aid with the determination of the malignant transformation potential of oral dysplasias, although moderately and poorly differentiated tumors exhibited a significantly higher density of myofibroblasts. The results reinforce the hypothesis that myofibroblasts may contribute to oral tumorigenesis, indicating that verification and monitoring of such may serve as a putative marker of OSCC behavior. PMID:25621035

RODRIGUES, PRISCILA CAMPIONI; DA COSTA MIGUEL, MÁRCIA CRISTINA; DE AQUINO, SIBELE NASCIMENTO; FONSECA, FELIPE PAIVA; SILVA, ALAN ROGER DOS SANTOS; LEME, ADRIANA FRANCO PAES; COLETTA, RICARDO D.

2015-01-01

5

Malignant transformation in 5071 southern Taiwanese patients with potentially malignant oral mucosal disorders  

PubMed Central

Background Oral cancers can be preceded by clinically evident oral potentially malignant disorders (OPMDs). The current study evaluated the rate and the time of malignant transformation in the various OPMDs in a cohort of patients from southern Taiwan. Parameters possibly indicative for malignant transformation of OPMDs, such as epidemiological and etiological factors, and clinical and histopathological features were also described. Methods We followed-up 5071 patients with OPMDs—epithelial dysplasia with oral submucous fibrosis, epithelial dysplasia with hyperkeratosis/epithelial hyperplasia, hyperkeratosis/epithelial hyperplasia, oral submucous fibrosis, lichen planus, and verrucous hyperplasia—between 2001 and 2010 for malignant transformation. Results Two hundred nineteen of these 5071 OPMD patients (202 men, 17 women; mean age: 51.25 years; range: 30–81 years) developed oral cancers (179 squamous cell carcinomas; 40 verrucous carcinomas) in the same sites as the initial lesions at least 6 months after their initial biopsies. The overall transformation rate was 4.32% (mean duration of transformation: 33.56 months; range: 6–67 months). Additionally, the mean time of malignant transformation was significantly shorter for lesions with than without epithelial dysplasia. The risk of malignant transformation was 1.89 times higher for epithelially dysplastic than non-dysplastic lesions. The anatomical site of OPMD and the presence of epithelial dysplasia were significantly associated with malignant transformation. The hazard rate ratio was 1.87 times larger for tongue lesions than for buccal lesions. Conclusion Patients with OPMDs require long-term follow up. PMID:25096230

2014-01-01

6

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

PubMed

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

Matsumoto, Kanako

2011-06-01

7

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

8

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. PMID:25024833

Mortazavi, Hamed; Baharvand, Maryam; Mehdipour, Masoumeh

2014-01-01

9

Orally active vitamin d for potential chemoprevention of posttransplant malignancy.  

PubMed

Posttransplant malignancy (PTM) is a limiting factor both for patient and allograft survival in kidney transplant recipients (KTRs). We hypothesized that active vitamin D compounds (AVD) could reduce PTM development in KTRs. Ambulatory KTRs in a Japanese prospective cohort were followed from August 2007 to November 2010. The outcome of interest was newly diagnosed PTM. A propensity score (PS) of having received AVDs was estimated using 26 clinically relevant factors. We used the Cox proportional hazards model with stratification by PS tertiles on the assumption that baseline hazard functions differ among tertiles. As sensitivity analyses, we used inverse probability weighting and PS matching. Among 218 participants, the median age was 50 (interquartile range [IQR], 40 to 59) years, 63.3% were male, median time since transplantation was 11.2 (IQR, 5.2 to 17.1) years, and mean estimated GFR was 41.3 (SD, 15.6) mL/min per 1.73 m(2). At baseline, 42.2% had been treated with AVDs mainly for glucocorticoid-induced osteoporosis. AVDs used were calcitriol (58.7%) and alfacalcidol (41.3%). During follow-up, PTM developed in 5.4% of 92 AVD users and 8.7% of 126 nonusers. Poor vitamin D status was common in the participants, but the serum 25-hydroxyvitamin D level was not significantly associated with PTM in Cox regression analysis. After stratifying patients by PS tertiles, we found that AVDs were significantly associated with a lower risk of PTM (HR 0.25 [0.07 to 0.82]). Sensitivity analyses yielded similar results. AVDs are potential chemopreventive agents against PTM in KTRs. PMID:22926340

Obi, Yoshitsugu; Ichimaru, Naotsugu; Hamano, Takayuki; Tomida, Kodo; Matsui, Isao; Fujii, Naohiko; Okumi, Masayoshi; Kaimori, Jun-Ya; Yazawa, Koji; Kokado, Yukito; Tsubakihara, Yoshiharu; Nonomura, Norio; Rakugi, Hiromi; Takahara, Shiro; Isaka, Yoshitaka

2012-10-01

10

Oral potentially malignant disorders: A proposal for terminology and definition with review of literature  

PubMed Central

Several attempts to produce internationally accepted terminologies and definitions of ‘oral precancer’ have appeared in the literature. World Health Organizations (WHO) in 1972 subdivided ‘precancer’ into ‘lesions’ and ‘conditions’ with their definitions. Recent working group of WHO is not in favor of such subdivision and recommended the use of the term ‘oral potentially malignant disorder (OPMD)’. This is mainly attributed to the recent advancement in molecular and genetic aspects of ‘oral precancer’. But efforts to define OPMDs are few in the literature. ‘Oral precancer’ is ultimately colligated to oral squamous cell carcinoma (OSCC). With this semantics in mind, different OPMD and related terminologies in the literature used till date with their lexicographic analysis have been reviewed in the present paper. Attempt has also been made to propose desirable terminology and definition which suits to the current concept of OPMD. The proposed terminology and definition is based on the authors’ opinions with a hope for further suggestions from readers. PMID:25364185

Sarode, Sachin C; Sarode, Gargi S; Tupkari, Jagdish V

2014-01-01

11

Interdependence of Antioxidants and Micronutrients in Oral Cancer and Potentially Malignant Oral Disorders: A Serum and Saliva Study  

PubMed Central

Objective: In our previous studies we have evaluated the role of antioxidants and trace elements in potentially malignant disorders and cancers of the oral cavity, taking into consideration the importance of antioxidants as biomarkers in cancer detection. We felt that other than evaluation, the correlation and interdependence that existed among antioxidants and trace elements require further evaluation in order to develop a better understanding. Materials and Methods: Serum and salivary zinc, glutathione, and superoxide dismutase levels were evaluated in 65 healthy controls, 115 subjects with potentially malignant oral disorders, and 50 subjects with oral squamous cell carcinoma, using the atom absorption photometry, [5, 5-Dithiobis (2 nitrobenzoic acid)], and nitroblue tetrazolium methods, respectively. Results: Serum zinc and serum glutathione showed significant positive correlation (r=0.76, P=0.01). Similarly, salivary glutathione and salivary zinc levels had a positive correlation (r=0.68, P=0.01). Serum superoxide dismutase showed a strong positive correlation with serum zinc (r=0.64, P=0.01). Similarly, there was a moderate positive correlation between salivary superoxide dismutase and salivary zinc (r=0.67, P=0.01). Conclusion: Our findings showed that trace elements and antioxidants exhibited interdependence in serum, as well as in saliva, in both physiologic and pathologic states such as oral cancer. PMID:25628700

Shetty, Shishir Ram; Babu, Subhas G; Rao, Prasanna Kumar; Kishor, Sham Kannepady; Rao, Kumuda Arvind; Castelino, Renita

2014-01-01

12

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

NASA Astrophysics Data System (ADS)

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

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

2012-02-01

13

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

PubMed

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

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

2011-04-01

14

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

NASA Astrophysics Data System (ADS)

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

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

2014-01-01

15

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. PMID:20214513

DeCoro, Michael; Wilder-Smith, Petra

2014-01-01

16

Potentially malignant disorders of the oral cavity: current practice and future directions in the clinic and laboratory.  

PubMed

Despite commendable progress in the prevention, detection, and treatment of a wide variety of solid tumor types, oral squamous cell carcinoma (OSCC) remains a significant health burden across the globe. OSCC carcinogenesis involves accumulation of genetic alterations that coincide with the multistep malignant transformation of normal oral epithelium. OSCC is often first diagnosed at late stages of the disease (advanced regional disease and/or metastasis). Delayed diagnosis precludes successful treatment and favorable outcomes. In clinical practice, opportunities exist to identify patients with oral potentially malignant disorders (OPMDs), which precede the development of cancer. This review addresses the current status of laboratory and clinical research on OPMDs, with emphasis on leukoplakia and erythroplakia. OSF is also presented, though there is a paucity of published studies on this disorder. We focus on findings that could translate into earlier diagnosis and more efficacious treatment of those lesions with significant malignant potential. We explore how markers of OPMD malignant transformation might be implemented into current diagnostic practice to help clinicians objectively stratify patients into treatment/follow-up groups according to relative risk. We provide an overview of recently concluded and ongoing OPMD chemoprevention trials. We describe laboratory OPMD models that can be used to not only to reveal the genetic and molecular intricacies of oral cancer but also to develop novel screening methods and therapeutic approaches. Finally, we call for targeted screening programs of at-risk populations in order to facilitate diagnosis and treatment of OPMD and early OSCC. PMID:24482244

Dionne, Kalen R; Warnakulasuriya, Saman; Zain, Rosnah Binti; Cheong, Sok Ching

2015-02-01

17

Targeting of chemoprevention to high-risk potentially malignant oral lesions: challenges and opportunities.  

PubMed

Worldwide, oral cancer is responsible for 170,000 deaths per year. Intervention to prevent this disease is a long sought after goal. Chemoprevention studies have focused on clinicopathological features of potentially malignant lesions (PML) in an effort to prevent their progression to cancer. However, prediction of future behavior for such lesions is difficult and remains a major challenge to such intervention. Different approaches to this problem have been tested in the past 20years. Early genetic progression models identified critical regions of allelic imbalance at 3p and 9p, and provided the basis for molecular markers to identify progressing PMLs. Subsequently, technological advances, such as genome-wide high-throughput array platforms, computer imaging, visualization technology and next generation sequencing, have broadened the scope for marker development and have the potential of further improving our ability to identify high-risk lesions in the near future either alone or in combination. In this article, we examine the milestones in the development of markers for PML progression. We emphasize the critical importance of networks among scientists, health professionals and community to facilitate the validation and application of putative markers into clinical practice. With a growing number of new agents to validate, it is necessary to coordinate the design and implementation of strategies for patient recruitment, integration of marker assessment, and the final translation of such approaches into clinical use. PMID:25240917

Martinez, Victor D; MacAulay, Calum E; Guillaud, Martial; Lam, Wan L; Zhang, Lewei; Corbett, Kitty K; Rosin, Miriam P

2014-12-01

18

Estimation of serum ?2-microglobulin in potentially malignant disorders and squamous cell carcinoma of the oral cavity: A clinicopathological study  

PubMed Central

Background: Tumor markers are substances, which quantitatively changes in serum, during the tumor development, one such tumor marker is serum ?2-microglobulin (?2-m). The aim of this study was to establish the role of ?2-m as a biochemical parameter for diagnosis and prognosis of oral carcinoma by estimation of serum ?2-m levels in potentially malignant lesions, conditions, and oral squamous cell carcinoma. Materials and Methods: The study was carried out on 48 subjects (16 control, 8 oral submucous fibrosis, 8 oral leukoplakia, and 16 oral squamous cell carcinoma patients of different stages), conducted at department of Oral Medicine, Kothiwal Dental College, Moradabad, India. Under aseptic precautions, 5 ml venous blood was drawn and serum was separated. Estimation of ?2-m level in serum was carried out by enzyme linked immunosorbent assay. The data were analyzed by using the statistical package for social sciences (SPSS 17.0) software. Cases and controls were tested for statistical significance with one-way ANOVA with post-hoc Tukey's HSD. Values of P < 0.05 were considered significant. Results: The mean serum ?2-m level in the control group was 1.173 ± 0.059, in potentially malignant lesions/conditions group was 1.688 ± 0.137 and in oral squamous cell carcinoma group was 2.835 ± 0.0313. This progressive increase in serum ?2-m level was found to be highly significant (P value < 0.001). Results of Receiver operating characteristic analysis showed ?2-m as a 100% sensitive and specific biomarker for oral squamous cell carcinoma. Conclusion: The present study establishes ?2-m as a specific biological tumor marker for diagnostic and prognostic evaluation of oral squamous cell carcinoma. PMID:24688569

Singh, Anand Pratap; Kumar, Nitin; Raju, Manthena Srinivasa; Singh, Narendra Nath; Nagendrareddy, Suma Gundareddy

2014-01-01

19

Gene Expression Profiling for the Purposes of Biomarker Discovery in Oral Potentially Malignant Lesions: A Systematic Review  

PubMed Central

Early and accurate diagnosis of oral potentially malignant lesions (OPML) is of critical importance in preventing malignant transformation. Although histopathological interpretation of the degree of epithelial dysplasia is considered the gold standard for diagnosis, this method is subjective and lacks sensitivity. Therefore, many attempts have been made to identify objective molecular biomarkers to improve diagnosis. Microarray technology has the advantage of screening the expression of the whole genome making it one of the best tools for searching for novel biomarkers. However, microarray studies of OPMLs are limited, and no review has been published to highlight and compare their findings. In this paper, we systematically review all studies that have incorporated microarray analyses in the investigation of gene profile alterations in OPMLs and suggest a set of commonly dysregulated genes across multiple gene expression profile studies. This list of common genes may help focus selection of markers for further analysis regarding their importance in the diagnosis and prognosis of OPMLs. PMID:24250244

AbdulMajeed, Ahmad A.; Farah, Camile S.

2013-01-01

20

Gene expression profiling for the purposes of biomarker discovery in oral potentially malignant lesions: a systematic review.  

PubMed

Early and accurate diagnosis of oral potentially malignant lesions (OPML) is of critical importance in preventing malignant transformation. Although histopathological interpretation of the degree of epithelial dysplasia is considered the gold standard for diagnosis, this method is subjective and lacks sensitivity. Therefore, many attempts have been made to identify objective molecular biomarkers to improve diagnosis. Microarray technology has the advantage of screening the expression of the whole genome making it one of the best tools for searching for novel biomarkers. However, microarray studies of OPMLs are limited, and no review has been published to highlight and compare their findings. In this paper, we systematically review all studies that have incorporated microarray analyses in the investigation of gene profile alterations in OPMLs and suggest a set of commonly dysregulated genes across multiple gene expression profile studies. This list of common genes may help focus selection of markers for further analysis regarding their importance in the diagnosis and prognosis of OPMLs. PMID:24250244

Abdulmajeed, Ahmad A; Farah, Camile S

2013-01-01

21

Leuloplakia - Review of A Potentially Malignant Disorder  

PubMed Central

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

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

2014-01-01

22

Correlated analysis of semi-quantitative immunohistochemical features of E-cadherin, VEGF and CD105 in assessing malignant potentiality of oral submucous fibrosis.  

PubMed

Oral submucous fibrosis, a potentially premalignant condition for oral squamous cell carcinoma, manifests both non-dysplastic and dysplastic grades. Early and specific identification of its malignant potentiality suffers from diagnostic limitations that may be addressed by correlated molecular pathology attributes having histopathological backdrop. Present study correlates expressional alteration in prime epithelial marker E-cadherin, with neo-angiogenic molecules viz. VEGF and CD105 for elucidation of malignant potentiality in different stages of oral submucous fibrosis. Sixty-eight incision biopsies from normal oral mucosa (n = 10), non-dysplastic (n = 18) and different dysplastic grades (n = 40) of oral submucous fibrosis were semi-quantitatively analyzed for immunohistochemical expressions of E-cadherin (membranous and cytoplasmic), VEGF and CD105 which were further statistically correlated. The loss of membranous E-cadherin with increase in cytoplasmic accumulation in differentiative layers of epithelium through the progression of dysplasia was noted along with up-regulation in VEGF expressions. The number of CD105(+) blood vessels and their major axis also showed significant increase from non-dysplasia toward higher grades of dysplasia. The positive correlation between deregulated expression of epithelial cell-cell adhesion molecule and increase in neo-angiogenic attributes of oral submucous fibrosis with increase in dysplastic grades indicated elucidatory potential of molecular expression features in assessment of malignant potentiality in oral submucous fibrosis. PMID:25015036

Anura, Anji; Das, Raunak Kumar; Pal, Mousumi; Paul, Ranjan Rashmi; Ray, Ajoy Kumar; Chatterjee, Jyotirmoy

2014-12-01

23

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

24

Noninvasive imaging of oral premalignancy and malignancy  

NASA Astrophysics Data System (ADS)

Objectives: Early detection of cancer and its curable precursors remains the best way to ensure patient survival and quality of life. Despite significant advances in treatment, oral cancer still results in 10,000 U.S. deaths annually, mainly due to the late detection of most oral lesions. Specific aim was to use a combination of non-invasive optical in vivo technologies to test a multi-modality approach to non-invasive diagnostics of oral premalignancy and malignancy. Methods: In the hamster cheek pouch model (120 hamsters), in vivo optical coherence tomography (OCT) and optical Doppler tomography (ODT) mapped epithelial, subepithelial and vascular change throughout carcinogenesis in specific, marked sites. In vivo multi-wavelength multi-photon (MPM) and second harmonic generated (SHG) fluorescence techniques provided parallel data on surface and subsurface tissue structure, specifically collagen presence and structure, cellular presence, and vasculature. Images were diagnosed by 2 blinded, pre-standardized investigators using a standardized scale from 0-6 for all modalities. After sacrifice, histopathological sections were prepared and pathology evaluated on a scale of 0-6. ANOVA techniques compared imaging diagnostics with histopathology. 95% confidence limits of the sensitivity and specificity were established for the diagnostic capability of OCT/ODT+ MPM/SHG using ROC curves and kappa statistics. Results: Imaging data were reproducibly obtained with good accuracy. Carcinogenesis-related structural and vascular changes were clearly visible to tissue depths of 2mm. Sensitivity (OCT/ODT alone: 71-88%; OCT+MPM/SHG: 79-91%) and specificity (OCT alone: 62-83%;OCT+MPM/SHG: 67-90%) compared well with conventional techniques. Conclusions: OCT/ODT and MPM/SHG are promising non-invasive in vivo diagnostic modalities for oral dysplasia and malignancy. Supported by CRFA 30003, CCRP 00-01391V-20235, NIH (LAMMP) RR01192, DOE DE903-91ER 61227, NIH EB-00293 CA91717, NSF BES-86924, AFOSR FA 9550-04-1-0101.

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

2005-04-01

25

Primary oral malignant melanoma: Clinicopathological series of four cases  

PubMed Central

Melanoma of the oral cavity is a rare malignant disease. On account of the presence at relatively obscure areas in the oral cavity, most of oral malignant melanomas are diagnosed at a late stage. Early diagnosis is essential for successful treatment and perhaps is the key factor in improving the prognosis of oral malignant melanoma. However, no large clinical series exist, and in fact, clinical cases are the sole key source of information. We hereby present a series of four cases of primary oral malignant melanoma of South-East Asian ethnic origin, with long-term, regular follow-up. The age of the patients ranged between 40 and 70 years, with equal sex predilection, and the gingiva was found to be the most common site of its occurrence. Based on clinical and histological parameters, all the cases were diagnosed as primary malignant melanoma, which were further confirmed by using immunohistochemical markers. PMID:23087742

Kumar, Ajay; Bindal, Ruchi; Shetty, Devi C.; Singh, Harkanwal P.

2012-01-01

26

Oral infections and septicemia in immunocompromised patients with hematologic malignancies.  

PubMed

To estimate the role of oral infections during septicemic episodes in immunocompromised patients with hematologic malignancies, 78 febrile episodes in 46 patients were monitored with daily clinical and microbiological investigations. The 19 septicemic episodes did not differ from the 59 other febrile episodes in the qualitative composition of the aerobic and facultatively anaerobic oral microflora or in the presence of teeth or acute oral infections on day 1. The oral prevalence rates of members of the family Enterobacteriaceae were higher on days 10, 11, and 12 in the febrile episodes with septicemia when compared with those of febrile episodes without septicemia. The prevalence of a probable oral focus in septicemia was 10.5%, and the prevalence of a probable or possible oral origin in septicemia was 31.6%. The results suggest that prevention and elimination of oral infections may reduce the morbidity and perhaps even the mortality in these patients. PMID:3182997

Bergmann, O J

1988-10-01

27

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. PMID:24130575

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

2013-01-01

28

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. PMID:23738507

2013-01-01

29

Clinical systemic lupeol administration for canine oral malignant melanoma  

PubMed Central

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

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

2015-01-01

30

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. PMID:24632862

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

2014-01-01

31

Malignant epithelioid schwannoma of the oral cavity in a cat.  

PubMed

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. PMID:24632862

Boonsriroj, Hassadin; Kimitsuki, Kazunori; Akagi, Tetsuya; Park, Chun-Ho

2014-06-01

32

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

PubMed Central

Background Oral cancer survival rates increase significantly when it is detected and treated early. Unfortunately, clinicians now lack tests which easily and reliably distinguish pre-malignant oral lesions from those already transitioned to malignancy. A test for proteins, ones found in non-invasively-collected whole saliva and whose abundances distinguish these lesion types, would meet this critical need. Methodology/Principal Findings To discover such proteins, in a first-of-its-kind study we used advanced mass spectrometry-based quantitative proteomics analysis of the pooled soluble fraction of whole saliva from four subjects with pre-malignant lesions and four with malignant lesions. We prioritized candidate biomarkers via bioinformatics and validated selected proteins by western blotting. Bioinformatic analysis of differentially abundant proteins and initial western blotting revealed increased abundance of myosin and actin in patients with malignant lesions. We validated those results by additional western blotting of individual whole saliva samples from twelve other subjects with pre-malignant oral lesions and twelve with malignant oral lesions. Sensitivity/specificity values for distinguishing between different lesion types were 100%/75% (p?=?0.002) for actin, and 67%/83% (p<0.00001) for myosin in soluble saliva. Exfoliated epithelial cells from subjects' saliva also showed increased myosin and actin abundance in those with malignant lesions, linking our observations in soluble saliva to abundance differences between pre-malignant and malignant cells. Conclusions/Significance Salivary actin and myosin abundances distinguish oral lesion types with sensitivity and specificity rivaling other non-invasive oral cancer tests. Our findings provide a promising starting point for the development of non-invasive and inexpensive salivary tests to reliably detect oral cancer early. PMID:20567502

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

2010-01-01

33

Efficacy of oral brush cytology in the evaluation of the oral premalignant and malignant lesions  

PubMed Central

Objective: In the present study, oral brush cytology of premalignant and malignant lesions was performed using tooth brush. The cytopathological diagnosis of brush cytology was compared with that of punch biopsy. The reliability of oral brush cytology using tooth brush was assessed in terms of sensitivity and specificity. Materials and Methods: A total of 67 patients, 32 premalignant lesions and other 35 frank oral carcinomas, were included in the study. All patients underwent oral brush cytology using a toothbrush followed by punch biopsy. Sensitivity, specificity, positive and negative predictive values were calculated. Cytopathology and histopathology of premalignant and malignant lesions were compared using Mann-Whitney U test. Inter- and intra-examiner reliability was calculated using Rank-correlation coefficient. Results: Two in premalignant group and five in malignant group were marked insufficient. 18% of cases were false negatives. The sensitivity, specificity, positive predictive value and negative predictive value were 77%, 100%, 100% and 38%, respectively. Statistical analysis showed P>0.05, suggesting that there is no significant difference between histopathology and brush cytology in assessing both premalignant and malignant lesions. Inter- and intra-examiner reliability were 99.22% and 99.77%, respectively. Conclusion: Brush cytology using a tooth brush is reliable and can be easily performed with less cost and discomfort to the patient. It is useful in those situations when a patient refuses to have a biopsy performed or when medically compromised patients would be exposed to unnecessary surgical risks. It can be used for screening for suspicious oral lesions, and may have applications in resource-challenged areas. PMID:22090689

Babshet, M; Nandimath, K; Pervatikar, SK; Naikmasur, VG

2011-01-01

34

Treatment Option Overview (Ovarian Low Malignant Potential Tumors)  

MedlinePLUS

... types of treatment for patients with ovarian low malignant potential tumor. Different types of treatment are available for patients with ovarian low malignant potential tumor . Some treatments are standard (the currently ...

35

Clinical study for classification of benign, dysplastic, and malignant oral lesions using autofluorescence  

E-print Network

for classification of benign versus (pre-)malignant mucosa for all methods (0.50 to 0.70). Some statisticallyClinical study for classification of benign, dysplastic, and malignant oral lesions using significant differences between surrounding/contralateral tissues of benign and healthy tissue and of (pre

Duin, Robert P.W.

36

MicroRNA expression profiling and functional annotation analysis of their targets associated with the malignant transformation of oral leukoplakia.  

PubMed

In spite the tremendous achievements that have been acquired in the field of molecular biology, the underlying mechanism associated with malignant transformed oral leukoplakia (OLK) is still unclear and poorly understood. The aim of this study is to investigate the microRNA (miRNA) expression profiles in OLK and its aggressive transformed tissues from the white lesion of human oral mucosa. The original miRNA expression dataset was downloaded from Gene Expression Omnibus (GEO) database and differentially expressed miRNAs were identified using two-sample t test method. Unsupervised hierarchical clustering and principal component analysis of these differentially expressed miRNAs indicated that 38-miRNA candidates could significantly discriminate OLK from malignant transformed oral mucosa samples. Besides, potential transcription factors were predicted using CyTargetLinker plugin and the miRNA-mRNA regulatory network associated with the malignant pathogenesis was visualized in Cytoscape environment. Totally, 3-miRNA signatures (miR-129-5p, miR-339-5p and miR-31*) were found to be hubs that mediated the initiation and progression of OLK from the non-malignant to the aggressive one via targeting various transcription factors. Functional enrichment analysis based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested that the dysregulation of immune response was responsible for oral carcinogenesis. In conclusion, we constructed a miRNA-mRNA regulatory network associated with the malignant transformation of OLK, and screened out some miRNAs and transcription factors that may have prominent roles during OLK malignant progression. PMID:25576219

Maimaiti, Aikebaier; Abudoukeremu, Kaisaier; Tie, Lu; Pan, Yan; Li, Xuejun

2015-03-10

37

Characteristics of oral and paraoral malignant lymphoma: A population-based review of 361 cases  

Microsoft Academic Search

Background: Lymphoma is the second most common neoplasm of the head and neck; almost 50% of all lymphomas occur in this region. Waldeyer's ring is the most common site of lymphomas involving the oral region. The purpose of this study was to review the characteristics of a large series of malignant lymphoma of the oral region. Methods: Three hundred sixty-one

Joel B. Epstein; Joshua D. Epstein; Nhu D. Le; Meir Gorsky

2001-01-01

38

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

PubMed

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

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

2015-01-01

39

Automated classification of optical coherence tomography images for the diagnosis of oral malignancy in the hamster cheek pouch.  

PubMed

Most studies evaluating the potential of optical coherence tomography (OCT) for the diagnosis of oral cancer are based on visual assessment of OCT B-scans by trained experts. Human interpretation of the large pool of data acquired by modern high-speed OCT systems, however, can be cumbersome and extremely time consuming. Development of image analysis methods for automated and quantitative OCT image analysis could therefore facilitate the evaluation of such a large volume of data. We report automated algorithms for quantifying structural features that are associated with the malignant transformation of the oral epithelium based on image processing of OCT data. The features extracted from the OCT images were used to design a statistical classification model to perform the automated tissue diagnosis. The sensitivity and specificity of distinguishing malignant lesions from benign lesions were found to be 90.2% and 76.3%, respectively. The results of the study demonstrate the feasibility of using quantitative image analysis algorithms for extracting morphological features from OCT images to perform the automated diagnosis of oral malignancies in a hamster cheek pouch model. PMID:25162909

Pande, Paritosh; Shrestha, Sebina; Park, Jesung; Serafino, Michael J; Gimenez-Conti, Irma; Brandon, Jimi; Cheng, Yi-Shing; Applegate, Brian E; Jo, Javier A

2014-08-01

40

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

NASA Astrophysics Data System (ADS)

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

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

2014-09-01

41

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

SciTech Connect

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

Yamada, Tamaki [Laboratory of Pathophysiology and Signal Transduction, Department of Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Division of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, N13W7, Kita-ku, Sapporo 060-8586 (Japan); Laboratory of Oral and Maxillofacial Surgery, Hokkaido University Graduate School of Dental Medicine, N13W7, Kita-ku, Sapporo 060-8586 (Japan); Tsuda, Masumi [Laboratory of Pathophysiology and Signal Transduction, Department of Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Ohba, Yusuke [Laboratory of Pathophysiology and Signal Transduction, Department of Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)], E-mail: yohba@med.hokudai.ac.jp; Kawaguchi, Hideaki [Laboratory of Pathophysiology and Signal Transduction, Department of Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Totsuka, Yasunori [Laboratory of Oral and Maxillofacial Surgery, Hokkaido University Graduate School of Dental Medicine, N13W7, Kita-ku, Sapporo 060-8586 (Japan); Shindoh, Masanobu [Division of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, N13W7, Kita-ku, Sapporo 060-8586 (Japan)

2008-04-11

42

Paraganglioma of the pancreas: a potentially functional and malignant tumor  

PubMed Central

Paragangliomas are neoplasms that arise from extra-adrenal chromaffin cells. Pancreatic paragangliomas are rare, and few are malignant. To the best of our knowledge, no cases of functional pancreatic paragangliomas have been reported in the literature to date. We present two cases of pancreatic paragangliomas with pathological confirmation. In the case 1, clinical testing and pathological analysis revealed functional and malignant characteristics of the tumor, which carried a poor prognosis. In case 2, functional paraganglioma was suspected. The clinical presentations and outcomes of these two patients are summarized, and the relevant literature is reviewed. Because of the small number of cases reported previously, few characteristics of these tumors are known. The best methods of predicting the malignant and functional potential of these tumors remain unknown. We propose careful preoperative treatment and close postoperative follow-up of paraganglioma patients because of the functional and malignant potential of these tumors. PMID:25030833

2014-01-01

43

Long-term survival in metastatic malignant struma ovarii treated with oral chemotherapy: A case report.  

PubMed

Malignant struma ovarii is a rare type of ovarian tumor. Metastasis from malignant struma ovarii is rare and has only been documented in 5-6% of cases. The natural history and optimal treatment strategy for malignant struma ovarii remains controversial due to its rarity. The current report presents the case of a 45-year-old female who presented with a tumor of the rib bone. Following resection, the postoperative diagnosis was a metastasizing thyroid carcinoma. No abnormality was detected in the thyroid gland, however, computed tomography revealed a tumor in the left ovary. The patient underwent a left salpingo-oophorectomy and a wedge resection of the right ovary. The postoperative diagnosis was determined as a mature cystic teratoma with malignant struma ovarii (thyroid type, follicular carcinoma) of the left ovary and mature cystic teratoma of the right ovary. Four years subsequent to the initial diagnosis, multiple lung metastases were detected. The following chemotherapies were administered sequentially and intermittently: Tegafur-uracil, paclitaxel/carboplatin and oral etoposide. During this period, the metastatic lesions extended into the bone and progressed slowly. The patient continues to survive with the disease and 24 years have passed since the initial diagnosis, 20 years following the diagnosis of multiple lung metastates. The present report describes a rare case of malignant struma ovarii in which surgical resection and pathological examination of a metastatic rib tumor resulted in the identification of the primary ovarian lesion. The clinical behavior of malignant struma ovarii does not necessarily indicate a histological malignancy, therefore, prediction of future metastasis is difficult and the optimal treatment strategy for malignant struma ovarii is controversial. The present case indicates that the long-term use of oral anticancer agents may facilitate the maintenance of tumor dormancy. PMID:25364407

Ukita, Masayo; Nakai, Hidekatsu; Kotani, Yasushi; Tobiume, Takako; Koike, Eiji; Tsuji, Isao; Suzuki, Ayako; Mandai, Masaki

2014-12-01

44

Value of FDG PET/CT in Staging of Oral Cancer: Four Simultaneous Primary Malignancies.  

PubMed

Patients with squamous cell cancer (SCC) of the head and neck are at increased risk for second primary malignancies (SPMs). We report on a 53-year-old patient with primary diagnosis of SCC in the anterior floor of the mouth. Panendoscopy suspected an SPM of the right vocal cord. FDG PET/CT, as a whole-body imaging method, confirmed this suspicion and raised concern for further SPM of both esophagus and colon. All malignancies were confirmed by biopsy. Subsequently, the patient underwent radiochemotherapy. In summary, FDG PET/CT revealed unexpected multiple SPMs, prevented unnecessary resection of the oral SCC, and enabled individualized therapeutic management. PMID:25742223

Linz, Christian; Müller-Richter, Urs D A; Kircher, Stefan; Lapa, Constantin; Bluemel, Christina

2015-05-01

45

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

PubMed Central

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

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

2015-01-01

46

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

PubMed Central

Objective: To determine the epidemiological profile of malignant melanoma cases treated at the National Institute for Neoplastic Diseases “Dr. Eduardo Caceres Graziani” (INEN) over the period 1952 to 2008. Study Design: All clinical records with complete data of patients presenting a histopathological diagnosis of malignant melanoma of the oral cavity were reviewed. Data such as age, gender, location, tumor size, disease length, presence of metastasis, treatment received and year of admission were recorded. Results: During the study period 97 cases were found. The average age of patients was 52.85±1.6 years old mostly between 50 and 59 years old; the predominant gender was the female. The most common location was the palate and there was 58.8% of cases with a tumor size bigger than or equal to 4 cm. The length of the disease in 38.1% of the cases was longer than a year and in great part of the cases (69.1%) there was no metastasis. The treatment of choice was the surgery plus radiotherapy in 38.1% of the cases. According to the admission date it was also noted that the number of cases is increasing. Conclusion: The results of this study demonstrate a late diagnosis and an increasing frequency of this neoplasia in the oral cavity. Key words: Melanoma, oral cavity, epidemiology. PMID:22143709

Gutiérrez-Morales, Mario M.; Sacsaquispe-Contreras, Sonia J.; Sánchez-Lihón, Juvenal; Morales-Vadillo, Rafael

2012-01-01

47

Utility of toluidine blue test in accessing and detecting intra-oral malignancies.  

PubMed

In vivo staining reveals cytological details that might otherwise not be apparent. The aim of the study was to test the utility of toluidine blue test in detecting various types of malignant and premalignant lesions in early stage. Fifty patients with lesion in oral cavity having suspicion of malignancy clinically were selected. After subjecting the patients to clinical examination, the suspicious lesions were stained with 1 % toluidine blue. The biopsy site was selected on the basis of clinical appearance and dye retention and in the sites where no retention of the stain occurred, clinical judgment directed the biopsy site. The sensitivity of toluidine blue in detecting premalignant or malignant lesions was found to be 97.8 % and the over all specificity was found to be 100 %. The positive predictive value, negative predictive value and diagnostic accuracy was reported to be 100, 80 and 90 % respectively. Toluidine Blue staining is highly a reliable source for the detection of insitu and invasive carcinomas. Staining with this stains is an adjunct to clinical judgment, assist in the choice of biopsy site, follow up of premalignant lesions and marginal demarcation of the malignant lesions enabling an intervention method to be adopted earlier for the disease, which carries a high rate of morbidity and mortality. PMID:25621253

Singh, Deepti; Shukla, R K

2015-03-01

48

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

49

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

PubMed Central

Background Autofluorescence imaging is used widely for diagnostic evaluation of various epithelial malignancies. Cancerous lesions display loss of autofluorescence due to malignant changes in epithelium and subepithelial stroma. Carcinoma of unknown primary site presents with lymph node or distant metastasis, for which the site of primary tumour is not detectable. We describe here the use of autofluorescence imaging for detecting a clinically innocuous appearing occult malignancy of the palate which upon pathological examination was consistent with a metastatic squamous cell carcinoma. Case Description A submucosal nodule was noted on the right posterior hard palate of a 59-year-old white female during clinical examination. Examination of this lesion using a multispectral oral cancer screening device revealed loss of autofluorescence at 405 nm illumination. An excisional biopsy of this nodule, confirmed the presence of a metastatic squamous cell carcinoma. Four years ago, this patient was diagnosed with metastatic squamous cell carcinoma of the right mid-jugular lymph node of unknown primary. She was treated with external beam irradiation and remained disease free until current presentation. Conclusion This case illustrates the important role played by autofluorescence tissue imaging in diagnosing a metastatic palatal tumour that appeared clinically innocuous and otherwise would not have been biopsied. PMID:19863814

2009-01-01

50

IL-1? promotes malignant transformation and tumor aggressiveness in oral cancer.  

PubMed

Chronic inflammation, coupled with alcohol, betel quid, and cigarette consumption, is associated with oral squamous cell carcinoma (OSCC). Interleukin-1 beta (IL-1?) is a critical mediator of chronic inflammation and implicated in many cancers. In this study, we showed that increased pro-IL-1? expression was associated with the severity of oral malignant transformation in a mouse OSCC model induced by 4-Nitroquinolin-1-oxide (4-NQO) and arecoline, two carcinogens related to tobacco and betel quid, respectively. Using microarray and quantitative PCR assay, we showed that pro-IL-1? was upregulated in human OSCC tumors associated with tobacco and betel quid consumption. In a human OSCC cell line TW2.6, we demonstrated nicotine-derived nitrosamine ketone (NNK) and arecoline stimulated IL-1? secretion in an inflammasome-dependent manner. IL-1? treatment significantly increased the proliferation and dysregulated the Akt signaling pathways of dysplastic oral keratinocytes (DOKs). Using cytokine antibodies and inflammation cytometric bead arrays, we found that DOK and OSCC cells secreted high levels of IL-6, IL-8, and growth-regulated oncogene-? following IL-1? stimulation. The conditioned medium of IL-1?-treated OSCC cells exerted significant proangiogenic effects. Crucially, IL-1? increased the invasiveness of OSCC cells through the epithelial-mesenchymal transition (EMT), characterized by downregulation of E-cadherin, upregulation of Snail, Slug, and Vimentin, and alterations in morphology. These findings provide novel insights into the mechanism underlying OSCC tumorigenesis. Our study suggested that IL-1? can be induced by tobacco and betel quid-related carcinogens, and participates in the early and late stages of oral carcinogenesis by increasing the proliferation of dysplasia oral cells, stimulating oncogenic cytokines, and promoting aggressiveness of OSCC. PMID:25204733

Lee, Chia-Huei; Chang, Jeffrey Shu-Ming; Syu, Shih-Han; Wong, Thian-Sze; Chan, Jimmy Yu-Wai; Tang, Ya-Chu; Yang, Zhi-Ping; Yang, Wen-Chan; Chen, Chiung-Tong; Lu, Shao-Chun; Tang, Pei-Hua; Yang, Tzu-Ching; Chu, Pei-Yi; Hsiao, Jenn-Ren; Liu, Ko-Jiunn

2015-04-01

51

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

52

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

PubMed

To estimate clinical, pathogenic and serological aspects of acute oral candidiasis (AOC) during febril episodes in patients with haematologic malignancies, 23 consecutive patients who developed AOC within 7 days from start of fever were compared with 23 consecutive patients who did not develop AOC. The duration of fever and severe granulocytopenia (less than 0.5 x 10(9)/l) was significantly longer in patients with AOC than in patients without AOC, the median differences between the patients with and without AOC being 4 and 3 days, respectively. Development of AOC could not be correlated to a change in the qualitative composition of the oral microflora. The thrombocyte count was lower in patients with AOC on day 4, whereas no differences were found in leukocyte counts. The prevalences of Candida albicans agglutinin titres greater than or equal to 5 were similar in patients with (24%) and without AOC (33%), and in controls (29%). Seroconversion or a significant increase in the agglutinin titre occurred in 4 patients with AOC and long-lasting fever, who became afebrile after systemic antifungal therapy. It is concluded that AOC is associated with long-lasting fever and decreased bone marrow function as judged by low thrombocyte counts, but not related to specific bacteria in the oral cavity or to an increased occurrence of C. albicans antibodies in the serum. PMID:2196672

Bergmann, O J; Andersen, P L

1990-01-01

53

Toxicity of weekly oral topotecan in relation to dosage for gynecologic malignancies: a phase I study.  

PubMed

The aim of this study was to determine the dose of weekly oral topotecan that allows safe administration and to evaluate the pharmacokinetics of this dose in patients with recurrent gynecologic malignancies. The first cohort of patients received oral topotecan 6 mg/week administered orally on days 1, 8, and 15 of a 28-day regimen. A standard 3+3 dose-escalating phase design was used for dose levels II-V (8, 10, 12 and 14 mg/week). Toxicity was scored according to the Common Terminology Criteria for Adverse Events. Cumulative toxicity was summarized in the 6-12 mg/week combined cohort and 14 mg/week cohort separately. Pharmacokinetic samples were obtained for day 1, cycle 1 only in the expansion cohort (dose level V). Twenty-five patients received a total of 88 cycles of therapy. Hematologic toxicities of grade 3 (6-12 mg dose) were neutropenia (25%) and anemia (8.3%). Gastrointestinal toxicities of grade 3 were diarrhea (16.7%) and obstruction (8.3%, disease-related). Grade 3 or 4 (14 mg/week) hematologic toxicities consisted of neutropenia (38.5%), platelets (15.4%), anemia (15.4%), infection with neutropenia (7.7%), and thrombosis (7.7%). Gastrointestinal toxicities of grade 3 were diarrhea (7.7%), obstruction (7.7%), and vomiting (7.7%). One patient died secondary to neutropenic sepsis. One patient (4%; 95% confidence interval: 2.1, 22.3) showed a partial response and five patients (20%; 95% confidence interval: 7.6, 41.3) had stable disease. An oral topotecan dose of 14 mg/week for 3 consecutive weeks out of 4 is mostly associated with acceptable toxicities and may be considered for use in future single-agent phase II trials. PMID:22555194

von Gruenigen, Vivian E; Frasure, Heidi E; Smith, Deborah A; Fusco, Nancy L; Eaton, Susan M; DeBernardo, Robert L; Heugel, Anne M; Waggoner, Steven E

2012-08-01

54

Oral chemotherapy: potential benefits and limitations  

Microsoft Academic Search

Although oral chemotherapeutic agents have been available for the last 50 years, some reservations about their efficacy and\\u000a the limited interest of pharmaceutical companies have hampered their widespread use. This situation will probably change in\\u000a the near future as several new oral anticancer agents have been approved and there are more in development.\\u000a \\u000a Convenience and easiness of administration make of

Jaime Feliu Batlle; Enrique Espinosa Arranz; Javier de Castro Carpeńo; Enrique Casado Sáez; Pilar Zamora Auńón; Andrés Redondo Sánchez; Manuel González Barón

2004-01-01

55

[Classification and malignant potential of pancreatic cystic tumors].  

PubMed

Cystic lesions of the pancreas are increasingly diagnosed with a reported prevalence of 10?% in 70-year-old individuals. Despite their broad spectrum, most resected cystic lesions can be attributed to one of the following entities: intraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasms (MCN), serous cystic neoplasms (SCN), neuroendocrine cystic tumors (NECT), and solid pseudopapillary neoplasms (SPN). Among them, IPMN and MCN represent precursors of ductal adenocarcinoma, NECT and SPN are low-grade, potentially malignant lesions, and SCN are usually benign. Due to the not negligible morbidity and mortality rates in pancreatic surgery, even in highly specialized centers, an interdisciplinary preoperative stratification of pancreatic cystic lesions into high- and low-risk tumors is necessary in order to accurately select those cases that need to undergo immediate resection. The role of the pathologist is fundamental in both the preoperative assessment and in the postoperative classification, which determines prognosis, further treatment, and follow-up. PMID:25663186

Esposito, I; Schlitter, A M; Sipos, B; Klöppel, G

2015-02-01

56

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

57

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. PMID:23722134

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

2013-01-01

58

Evaluation of exfoliative cytology in the diagnosis of oral premalignant and malignant lesions: A cytomorphometric analysis  

PubMed Central

Background: Many oral squamous cell carcinomas (OSCCs) arise within regions that previously had premalignant lesion. Early diagnosis and prompt treatment of premalignant lesions offers the best hope of improving the prognosis in patients with OSCC. Exfoliative cytology is a simple and non-invasive diagnostic technique that could be used for early detection of oral premalignant and malignant lesions. This study was undertaken to evaluate the quantitative changes in nuclear area (NA), cytoplasmic area (CA) and nuclear-to-cytoplasmic ratio (NA/CA) in cytological buccal smears of oral leukoplakia with dysplasia (OLD) and OSCC patients while comparing with normal healthy mucosa. Materials and Methods: A quantitative study was conducted over 90 subjects including 30 cases each of OLD, OSCC and clinically normal oral mucosa. The smears obtained were stained with Papanicolaou (PAP) stain and cytomorphological assessment of the keratinocytes was carried out. The statistical tools included arithmetic mean, standard deviation, Chi-square test, analysis of variance, Tukey multiple comparison. P < 0.001 was considered as significant. Results: The mean NA of keratinocytes in the normal mucosa was 65.47 ± 4.77 ?m2 while for OLD it was 107.97 ± 5.44 ?m2 and 139.02 ± 8.10 ?m2 for that of OSCC. The differences show a statistically significant increment in NA (P < 0.001). There was significant reduction (P < 0.001) in the CA of keratinocytes from OSCC when compared with those from smears of OLD and normal mucosa with the values of 1535.80 ± 79.38 ?m2, 1078.51 ± 56.65 ?m2 and 769.70 ± 38.77 ?m2 respectively. The NA/CA ratio in the smears from normal oral mucosa, OLD and OSCC showed a mean value of 0.043 ± 0.004, 0.100 ± 0.008, 0.181 ± 0.015 respectively with a significant difference among the groups (P < 0.001). Conclusion: Evaluation of nuclear and CA of keratinocytes by cytomorphometry can serve as a useful adjunct in the diagnosis and prognosis of a dysplastic lesion which may lead to OSCC. PMID:25709680

Verma, Renuka; Singh, Anil; Badni, Manjunath; Chandra, Akhilesh; Gupta, Shalini; Verma, Ruchita

2015-01-01

59

Recognizing and overcoming potential barriers to oral medications for MS.  

PubMed

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

Moses, Harold

2014-10-01

60

Oral strip technology: overview and future potential.  

PubMed

Over the recent past, many of the research groups are focusing their research on this technology. Amongst the plethora of avenues explored for rapid drug releasing products, Oral Strip Technology (OST) is gaining much attention. The advantages of OST are the administration to pediatric and geriatric patient population where the difficulty of swallowing larger oral dosage forms is eliminated. This technology has been used for local action, rapid release products and for buccoadhesive systems that are retained for longer period in the oral cavity to release drug in controlled fashion. OST offers an alternate platform for molecules that undergo first pass metabolism and for delivery of peptides. The review article is an overview of OST encompassing materials used in OST, critical manufacturing aspects, applications, commercial technologies and future business prospects of this technology. PMID:19559740

Dixit, R P; Puthli, S P

2009-10-15

61

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

PubMed Central

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

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

2015-01-01

62

The management and site-specific prognostic factors of primary oral mucosal malignant melanoma.  

PubMed

Primary oral mucosal malignant melanoma (POMM) is uncommon. Its biological behavior is more aggressive than that of cutaneous malignant melanoma. Its site-specific prognostic factors and optimal management have not been determined yet. Retrospective POMM case analysis from peer-reviewed publications in the PubMed and Embase electronic database from January 1984 to December 2013, in which therapy and outcome data were available, was performed. A total of 151 primary cases were extracted from 39 peer-reviewed English literatures. The study population includes 63 males and 88 females with a medium age of 61 years. The treatment protocols include surgery alone (18%), radiotherapy alone (14%), surgery plus radiotherapy (14%), surgery plus chemotherapy (31%), as well as surgery plus chemoradiotherapy (15%) and chemoradiotherapy (8%). The male patients have a higher risk for metastasis than the female patients do (odds ratio [OR]; 3.41, P = 0.021). The POMM originating from specialized mucosa was associated with increased risk for tumor recurrence and mortality (OR, 4.03, P = 0.001; OR, 2.03, P = 0.031, respectively). The patients who had surgery-based multiple therapy have a significantly longer survival compared with those who had surgery alone and those who had no surgical treatment (P = 0.000). The age of 60 years or younger (hazard ratio [HR], 4.69; P = 0.000), nonsurgical treatment (HR, 12.838; P = 0.000), and surgery alone (HR, 1.517; P = 0.001) were independent adverse prognostic factors for overall survival. Taken together, the study results suggest that surgery-based multiple therapy is the most effective treatment protocol. The age of 60 years, nonsurgical treatment, and surgery alone were independent adverse prognostic factors for overall survival. PMID:25668115

Wushou, Alimujiang; Zhao, Ya-Jun

2015-03-01

63

Bacteriophage and their potential roles in the human oral cavity  

PubMed Central

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

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

2015-01-01

64

A potential peptide pathway from viruses to oral lichen planus.  

PubMed

Oral lichen planus is an idiopathic inflammatory disease of oral mucous membranes, characterized by an autoimmune epidermis attack by T cells. It remains unknown, however, how such aggressive T cells are activated in vivo to cause epidermal damage. This study analyzes the relationship at the peptide level between viruses and oral lichen planus disease. Four potentially immunogenic peptides (SSSSSSS, QEQLEKA, LLLLLLA, and MLSGNAG) are found to be shared between HCV, EBV, HHV-7, HSV-1, and CMV and three human proteins (namely pinin, desmoglein-3, and plectin). The described peptide sharing might be of help in deciphering the still unexplained immunopathogenic pathway that leads to oral lichen planus. J. Med. Virol. 87:1060-1065, 2015. © 2015 Wiley Periodicals, Inc. PMID:25776836

Lucchese, Alberta

2015-06-01

65

New orally active PDE4 inhibitors with therapeutic potential.  

PubMed

Structural optimization of pyrazolopyridine derivative 2, which is one of the newly discovered chemical leads for PDE4 inhibitors from our in-house library, was carried out successfully. The process of discovery of new orally active PDE4 inhibitors, which are expected to possess therapeutic potential, is presented and their structure-activity relationships are discussed. PMID:14684291

Ochiai, Hiroshi; Ishida, Akiharu; Ohtani, Tazumi; Kusumi, Kensuke; Kishikawa, Katuya; Obata, Takaaki; Nakai, Hisao; Toda, Masaaki

2004-01-01

66

High 18F-FDG Uptake For Uterine Smooth Muscle Tumor of Uncertain Malignant Potential.  

PubMed

Uterine smooth muscle tumor of uncertain malignant potential is rare. It can have recurrence metastasis but is much less aggressive than leiomyosarcoma. We report a case of a 42-year-old woman who underwent PET/CT scan, which showed intense F-FDG uptake in the uterus. Results of pathological examination after hysterectomy combined with bilateral oophorectomy were consistent with uterine smooth muscle tumor of uncertain malignant potential. PMID:25674868

Zhang, Ruiguo; Tian, Xun; Qin, Lan; Lu, Dongyan; Shen, Jie

2015-04-01

67

The Potential Role of Aurora Kinase Inhibitors in Haematological Malignancies  

PubMed Central

Summary Aurora kinases play an important role in the control of the cell cycle and have been implicated in tumourigenesis in a number of cancers. Among the haematological malignancies, overexpression of Aurora kinases has been reported in acute myeloid leukaemia, chronic myeloid leukaemia, acute lymphoblastic leukaemia, multiple myeloma, aggressive non-Hodgkin lymphoma and Hodgkin lymphoma. A large number of Aurora kinase inhibitors are currently in different stages of clinical development. In addition to varying in their selectivity for the different Aurora kinases, some also have activity directed at other cellular kinases involved in important molecular pathways in cancer cells. This review summarizes the biology of Aurora kinases and discusses why they may be good therapeutic targets in different haematological cancers. We describe preclinical data that has served as the rationale for investigating Aurora kinase inhibitors in different haematological malignancies, and summarize published results from early phase clinical trials. While the anti-tumour effects of Aurora kinase inhibitors appear promising, we highlight important issues for future clinical research and suggest that the optimal use of these inhibitors is likely to be in combination with cytotoxic agents already in use for the treatment of various haematological cancers. PMID:21980926

Farag, Sherif S.

2011-01-01

68

Effectiveness of vital staining with iodine solution in reducing local recurrence after resection of dysplastic or malignant oral mucosa.  

PubMed

The purpose of this retrospective study was to assess the effect of vital staining with iodine solution in reducing local recurrence after resection of dysplastic or malignant oral mucosa. The historical control group had dysplastic or malignant mucosal lesions resected solely on the evidence of direct inspection and palpation. In the vital staining group tissue was resected only after vital staining with iodine solution. Seven of 25 patients in the conventional group developed recurrent dysplastic or cancerous oral mucosa around the primary site, while no patient among 23 reported recurrence in the vital staining group (p<0.01). Kaplan-Meier assessment showed that the 5-year primary control rate was 100% in the vital staining group and 75% in the conventional group. Although this retrospective study has some limitations, the results suggest that vital staining with iodine may be useful in reducing the incidence of recurrence of dysplastic or cancerous epithelium at a primary site. Further well-controlled study is essential. PMID:21514705

Kurita, Hiroshi; Kamata, Takahiro; Li, Xiangjun; Nakanishi, Yoshitaka; Shimane, Tetsu; Koike, Takeshi

2012-03-01

69

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

PubMed

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

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

2014-04-01

70

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. PMID:8080738

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

1994-01-01

71

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. PMID:24913673

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

2014-01-01

72

Interleukin-1 receptor antagonist (IL1RN) is associated with suppression of early carcinogenic events in human oral malignancies.  

PubMed

Inflammatory abnormalities have been implicated in the pathogenesis of various human diseases, including cancer. Interleukin-1 receptor antagonist (IL1RN) is a potent anti-inflammatory molecule that modulates the biological activity of the proinflammatory cytokine, interleukin-1. The aim of this study was to examine the expression of IL1RN in oral squamous cell carcinomas (OSCCs), and to determine its clinical significance. Expression levels of IL1RN in matched normal and tumor specimens from 39 OSCCs were evaluated using real-time quantitative polymerase chain reaction methods, and immunohistochemical analysis. Protein expression of IL1RN was also examined in 18 oral premalignant lesions (OPLs). Expression of IL1RN mRNA was significantly downregulated in OSCCs compared with normal tissues. Decreased expression of IL1RN protein was also observed in OPLs and OSCCs. The IL1RN expression level was lower in the OPL cases with severe dysplasia compared to those with mild/moderate dysplasia. Significantly downregulated IL1RN expression was observed in all OSCC lesion sites examined when compared with the matched normal tissues. However, the decreased level of IL1RN expression did not correspond with tumor progression. Noteworthy, IL1RN expression was higher in the advanced OSCC cases (T3/T4) compared to early cases (T1/T2). Among OSCC samples, relatively higher IL1RN expression was associated with active tumor development in the OSCCs occurring in the buccal mucosa, oral floor, fauces and gingiva, but not the tongue. These data suggest that IL1RN may exhibit opposing characteristics in oral malignancies depending on the stage of cancer development, suppressing early carcinogenic events, yet promoting tumor development in some lesion sites. Thus, IL1RN could represent a reliable biomarker for the early diagnosis of OSCCs. Furthermore, IL1RN may possess unknown and complex functions in the developed OSCC. PMID:25738940

Shiiba, Masashi; Saito, Kengo; Yamagami, Hitomi; Nakashima, Dai; Higo, Morihiro; Kasamatsu, Atsushi; Sakamoto, Yosuke; Ogawara, Katsunori; Uzawa, Katsuhiro; Takiguchi, Yuichi; Tanzawa, Hideki

2015-05-01

73

Orally active PDE4 inhibitors with therapeutic potential.  

PubMed

Based on the successful results in the clinical trial of Ariflo, further optimization of the spatial arrangement of the three pharmacophores (carboxylic acid moiety, nitrile moiety and 3-cyclopentyl-4-methoxyphenyl moiety) in the structure of Ariflo 1 was attempted using a bicyclo[3.3.0]octane template instead of a cyclohexane template. As a result, 2a, 7a and 7b were found to be orally active and were predicted to have an improved therapeutic potential based on evaluation by cross-species and same-species comparisons. Structure-activity relationships (SARs) of these compounds are also discussed. PMID:14980691

Ochiai, Hiroshi; Ohtani, Tazumi; Ishida, Akiharu; Kishikawa, Katuya; Obata, Takaaki; Nakai, Hisao; Toda, Masaaki

2004-03-01

74

New orally active PDE4 inhibitors with therapeutic potential.  

PubMed

The design, synthesis, and biological evaluation of a series of pyrazolopyridines was carried out. Structural optimization of the aniline moiety of 4-anilinopyrazolopyridine derivative 3a, which is one of the newly discovered chemical leads for PDE4 inhibitors from our in-house library, was performed successfully. The details of the discovery of new orally active PDE4 inhibitors, which are expected to show therapeutic potential, are presented and their structure-activity relationships are discussed. Pharmacological evaluation and pharmacokinetic data for representative compounds are also presented. PMID:15246087

Ochiai, Hiroshi; Ishida, Akiharu; Ohtani, Tazumi; Kusumi, Kensuke; Kishikawa, Katuya; Yamamoto, Susumu; Takeda, Hiroshi; Obata, Takaaki; Nakai, Hisao; Toda, Masaaki

2004-08-01

75

Primary Retroperitoneal Mucinous Cystadenocarcinoma of Low Malignant Potential: A Case Report and Literature Review  

Microsoft Academic Search

A case of primary retroperitoneal mucinous cystadenocarcinoma of low malignant potential in the presence of normal ovaries is reported. The precise etiology of these neoplasms has not been defined; however, they may arise from heterotopic ovarian tissue, monodermal teratomas, embryonal urogenital remnants, intestinal duplication, or coelomic metaplasia. Although minimal data exist to define the appropriate management, it seems reasonable to

Michael L. Pearl; Fidel Valea; John Chumas; Eva Chalas

1996-01-01

76

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

PubMed

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

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

2013-06-01

77

Atypical fibroxanthoma of oral mucosa: a variant of malignant fibrous histiocytoma.  

PubMed

Atypical fibroxanthoma, a more recently recognised variant of malignant fibrous histiocytoma, is described arising at the site of an earlier squamous cell carcinoma, in a patient treated with radiotherapy 21 years previously. Distinction between atypical fibroxanthoma and a poorly-differentiated squamous cell carcinoma proved to be difficult by ordinary light microscopy and it was only after immunohistochemical staining that the second lesion was confirmed as atypical fibroxanthoma. The natural history, differential diagnosis and histological pitfalls of this poorly characterised mesenchymal lesion are discussed. PMID:2169861

High, A S; Hume, W J; Dyson, D

1990-08-01

78

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.

2006-02-01

79

[Malignant disease in potential renal transplant recipients--diagnostic and therapeutic chalenge].  

PubMed

Renal transplantation is the treatment of choice for many patients with end-stage renal disease. There are a few generally accepted contraindications to transplantation: active infection, malignancy, substance abuse or non-adherence to therapy, chronic illness with life expectancy of less than one year, and poorly controlled psychosis. Potential renal transplant candidates must undergo thorough screening for exclusion of malignant diseases, with an individual approach to each patient. Patients with a history of malignancy might be placed on the waiting list for renal transplantation after a waiting period, which depends on the type of tumor and individual patient characteristics, and there are no signs of tumor. This group of patients require careful surveillance during the waiting time, as well as after transplantation. PMID:22359910

Mihaljevi?, Dubravka; Basi?-Juki?, Nikolina; Jaki?, Marko

2011-01-01

80

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. PMID:22021749

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

2011-01-01

81

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

Microsoft Academic Search

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

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

2005-01-01

82

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

Microsoft Academic Search

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

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

2009-01-01

83

Accuracy of CT in predicting malignant potential of cystic pancreatic neoplasms  

PubMed Central

Background. Cystic lesions of the pancreas are being identified more frequently. Deciding which asymptomatic lesions can be safely followed with serial imaging and which require resection due to malignant potential is an increasingly common question. Current clinical practice is to rely on characteristics of the lesions on CT scan, and additional information from endoscopic ultrasound with fine-needle aspiration (EUS-FNA) and cyst fluid analysis or endoscopic retrograde pancreatography (ERCP) to assess malignant potential. Hypothesis. The malignant potential of pancreatic cystic lesions cannot be accurately predicted by CT scan. Methods. CT scans from 48 patients with cystic lesions of the pancreas were stripped of patient identifiers and retrospectively presented to two expert radiologists. The radiologists recorded specific characteristics of the lesions thought to be important in the differential diagnosis and their opinion of the likely diagnosis. Diagnostic accuracy was assessed by comparing the radiologists’ diagnoses to the final pathologic diagnosis after resection. To determine if clinical history, EUS-FNA or ERCP findings improved diagnostic accuracy, medical records were retrospectively reviewed and scored as either supporting or not supporting malignant potential of the lesion. Results. Specific diagnoses based on CT findings alone were correct in an average of 39% of the cases. Even when diagnoses were dichotomized as benign (43%) or potentially malignant (57%, papillary mucinous neoplasms, mucinous cystic neoplasms, cancer), determinations based on CT alone were accurate in an average of 61% of cases. Accuracy rates were 60.4 and 62.5% for the two radiologists, although there was only fair agreement between them (Kappa=0.28, 95% CI=(0.01–0.55), p=0.05). When all clinical information available was considered together as a single dichotomous indicator of malignant potential, the indicator was accurate in 90% of the cases (Kappa=0.73, 95% CI=(0.51–0.95, p<0.0001)). Conclusion. Specific preoperative diagnosis of pancreatic cystic neoplasms by CT alone is substantially inaccurate. Complementary tests such as EUS-FNA with fluid analysis and ERCP should be recommended to improve diagnosis especially if nonoperative treatment is planned. PMID:19088937

Hodges, Sally E.; Yagnik, Vivek; Morón, Fannie E.; Wu, Meng-Fen; Hilsenbeck, Susan G.; Raijman, Isaac L.; Charles Brunicardi, F.

2008-01-01

84

Orally active PDE4 inhibitor with therapeutic potential.  

PubMed

Based on the promising results obtained by the clinical trial of Ariflo, further optimization of the spatial arrangement of the three pharmacophores (the carboxylic acid moiety, nitrile moiety and 3-cyclopentyloxy-4-methoxyphenyl moiety) in the structure of Ariflo 1 was attempted using a bicyclo[3 ?3 ?0]octane template with more stereochemical diversity than the cyclohexane template of Ariflo 1. Biological evaluation of the decyanated analogs and further optimization of the cyclopentyloxy moiety of 2a-b were also performed. Among the compounds tested, 2a, 7a-b and 12a were found to be orally active and were estimated to have therapeutic potential based on cross-species and same-species comparisons. The structure-activity relationships (SARs) of these compounds were investigated and pharmacokinetic data for 2a and 7b were also obtained by single-dose studies in rats. PMID:15236836

Ochiai, Hiroshi; Ohtani, Tazumi; Ishida, Akiharu; Kishikawa, Katuya; Yamamoto, Susumu; Takeda, Hiroshi; Obata, Takaaki; Nakai, Hisao; Toda, Masaaki

2004-07-01

85

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

PubMed

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. PMID:24817964

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

2014-01-01

86

[HMGB1-a as potential target for therapy of hematological malignancies].  

PubMed

HMGB1 is a widely existing DNA-binding nuclear protein, participating in gene transcription, damage repair, recombination and stabilizing nucleosome construction. Under injury, infection and chemotherapy, HMGB1 can be released by nature immunocyte and necrosis cells as a DAMP, exerting pleiotropic biological effects by binding to RAGE, TLR and CXCL12, which lead to activation of CDC42, mitogen-activated protein kinases (MAPKs), c-IAP and NF-?B, thereby promoting angiogenesis, unlimited replicative potential, tissue invasion and metastasis. And it also involves in immune response by regulating immunocyte function as a immunocyte warning signal. Scholars have detected that HMGB1 is over expressed and released following chemotherapy and radiation therapy in cells of hematological malignancies, promoting malignant cell replication, decreasing therapeutic effect. Recently, endogenous HMGB1 has been implied to be an intrinsic modulator of autophagy and referenced to resistant to apoptosis in malignant hematosis cells. In contrast, through suppression of HMGB1 expression, tumor cell apoptosis and chemotherapeutic drug sensitivity were increased, which will be a new strategy for the treatment of hematological malignancies. In this article, the basic characteristics of HMGB1, including structure and biological features, and HMGB1 and tumors such as lymphoma, myeloproliferative neoplasms and acute myeloid leukemia are reviewed. PMID:24763043

Hu, Ya-Hui; Yang, Lu; Zhang, Chen-Guang

2014-04-01

87

The detection of oral pre- malignant lesions with an autofluorescence based imaging system (VELscopeTM) – a single blinded clinical evaluation  

PubMed Central

Objective The disease specific five-year survival rate especially for patients with advanced oral cancer has not improved significantly over the period of time. The most effective way of combating this dilemma is an early detection, diagnosis and eradication of early-stage lesions and their precursors. The use of VELscope® using an autofluorescence as a diagnostic tool might be useful in early detection of oral malignant lesions. Materials and methods 120 patients with suspicious oral premalignant lesions were examined with two examination methods. They were randomly divided into two groups. Group 1 was examined conventional with white-light and group 2 was examined additionally to the white-light-examination with an autofluorescence visualization device, VELscope®. Biopsies were obtained from all suspicious areas identified in both examination groups (n?=?52). The diagnostic strategies were compared regarding sensitivity and specificity. Results Based upon the result, use of the VELscope® leads to a higher sensitivity (22.0%), but regarding specificity the additional use of the VELscope® is inferior (8.4%). Conclusion The VELscope device is a simple, non-invasive test of the oral mucosa, which can help the experienced clinician to find oral precursor malignant lesions. PMID:23967796

2013-01-01

88

Soft tissue giant cell tumour of low malignant potential: a rare tumour at a rare site.  

PubMed

"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. PMID:24551690

Bhat, Amoolya; V, Geethamani; C, Vijaya

2013-12-01

89

Potential Effects of Dietary Folate Supplementation on Oral Carcinogenesis, Development  

E-print Network

papillomavirus (HPV) infection has been proven to modulate proliferative phenotypes of many cancers to folate supplementation. Recent studies of HPV infection in a signif- icant fraction of oral cancers now confirm HPV that the relationships between HPV infection, folate supplementation and oral cancer growth should be thor- oughly

Ahmad, Sajjad

90

Entrapment into nanoemulsions potentiates the anticancer activity of tocotrienols against the highly malignant (+SA) mouse mammary epithelial cells.  

PubMed

The highly malignant +SA mouse mammary epithelial cells were used as the model cell line over the years to establish the anticancer activity of tocotrienols. Tocotrienols, however, have poor oral bioavailability and were therefore entrapped into parenteral nanoemulsions for parenteral administration. The objective of this work was to test whether the activity of tocotrienols in lipid nanoemulsions against the +SA cells was retained. A secondary objective was to test whether stabilizing the nanoemulsions with poloxamer or sodium oleate would affect their activity. Nanoemulsions were found to be significantly more potent than tocotrienol/albumin conjugate. The IC50 values of the poloxamer and sodium oleate nanoemulsions were 3 and 6 microM, respectively, whereas the IC50 value of the conjugate was 10 microM. The antiproliferative activity of the nanoemulsions was also found to inversely correlate with particle size. No activity was observed with nanoemulsions loaded with alpha-tocopherol or vehicle, which confirmed the cytotoxic activity of tocotrienols and the potential use of nanoemulsions in cancer therapy. PMID:24734680

Alayoubi, Alaadin; Ayoub, Nehad M; Malaviya, Abhita; Sylvester, Paul W; Nazzal, Sami

2014-05-01

91

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

92

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

93

P33. Potential clinical relevance of in vitro migratory activity in malignant pleural mesothelioma  

PubMed Central

Background Malignant pleural mesothelioma (MPM) displays locally invasive behavior and local recurrence. Recently we demonstrated that MPM cells have a high migratory potential in vitro. Accordingly, in the present study the correlation of in vitro migration with histological subtype and clinical outcome has been investigated. Methods Five international cell lines and seventeen cell lines established in our laboratory were analyzed by long-term videomicroscopy. Average migrated distance was calculated for all cell lines and dichotomized to slow and fast migratory cells at the cut-off of 90 micron per day. Correlation of migratory potential and histological subtype was performed by Fisher’s exact test and by Mann-Whitney analysis. Kaplan-Meier analysis was performed for overall survival in the slow and fast migratory group. Results A total of 13 epitheloid, seven biphasic and two sarcomatoid lines were analyzed. There was no significant difference in the ratio of slow migratory potential in epitheloid and non-epitheloid cell lines (54% and 44%, respectively). However, biphasic cell lines showed a modestly increased albeit not significantly elevated migratory potential compared to epitheloid MPM cells. Interestingly, patients with high motility MPM cells had a non-significant decrease in median overall survival when compared to those with tumor cells characterized by slow migratory activity (255 vs. 338 days, respectively). Conclusions Based on the study panel of our MPM cell lines, there is a tendency for higher migratory activity in biphasic cell lines and for decreased overall survival for patients with highly migratory tumor cells. Accordingly, the high migratory potential of MPM cells may indeed be an important component of the malignant phenotype of MPM. Cell migration might be—beside its potential prognostic value—a promising new target for therapeutic intervention.

Garay, Tamás; Molnár, Eszter; László, Viktória; Hoda, Mir Alireza; Tímár, József; Klepetko, Walter; Berger, Walter; Döme, Balázs; Hegedus, Balázs

2014-01-01

94

Uterine smooth muscle tumors of uncertain malignant potential (STUMP): pathology, follow-up and recurrence  

PubMed Central

The term smooth uterine muscle of uncertain malignant potential (STUMPs) indicates a group of uterine smooth muscle tumors (SMTs) that cannot be diagnosed unequivocally as benign or malignant. Diagnosis, surgical management, and follow-up of this neoplasm remain controversial, especially in pre-menopausal women with fertility desire, due to the non aggressive behaviour and prolonged survival rate when compared to leiomyosarcomas. However, recurrence is estimated between 8.7% and 11% and may include delayed-recurrences. We reported five cases of uterine masses treated by surgical procedure diagnosed as STUMP on final pathology. Four patients underwent a total abdominal hysterectomy with or without salpingo-oophorectomy. One patient underwent excision of uterine mass and subsequent total abdominal hysterectomy plus bilateral salpingo-oophorectomy after the diagnosis of STUMP. All patients in our study remained recurrence-free to date (with a follow up period ranging from 6 to 81 months). Based on our experience and in consideration of the lack of consensus regarding the malignant potential, diagnostic criteria, gold-standard treatment and follow-up, we believe that close multidisciplinary management is mandatory in the event of STUMP. We suggest that gynaecologist, dedicated pathologist (with high level of expertize in gynaecological pathology) and oncologist should work as a team in the counselling and management of this neoplasm from detection till completion of follow up. Furthermore, we recommend immunohistochemistry to investigate the overexpression of p16 and p53 in order to identify the cohort of patients at increased risk of recurrence who may benefit from more aggressive surgical-oncological strategies. PMID:25550862

Dall’Asta, Andrea; Gizzo, Salvatore; Musarň, Andrea; Quarantał, Michela; Noventa, Marco; Migliavacca, Costanza; Sozzi, Giulio; Monica, Michela; Mautone, Daniele; Berretta, Roberto

2014-01-01

95

Swietenine: A potential oral hypoglycemic from Swietenia macrophylla seed  

Microsoft Academic Search

Swietenine, a tetranortriterpenoid, was isolated from the Swietenia macrophylla seeds. The in vivo hypoglycemic activity was evaluated against neonatal-streptozotocin induced type 2 diabetic rats. Oral administration of swietenine at 25 and 50 mg\\/kg body weight per day to diabetic rats was found to possess significant dose dependant hypoglycemic and hypolipidemic activity in type 2 diabetic rats.

Saikat Dewanjee; Anup Maiti; Anup K. Das; Subhash C. Mandal; Sankar P. Dey

2009-01-01

96

Swietenine: a potential oral hypoglycemic from Swietenia macrophylla seed.  

PubMed

Swietenine, a tetranortriterpenoid, was isolated from the Swietenia macrophylla seeds. The in vivo hypoglycemic activity was evaluated against neonatal-streptozotocin induced type 2 diabetic rats. Oral administration of swietenine at 25 and 50 mg/kg body weight per day to diabetic rats was found to possess significant dose dependant hypoglycemic and hypolipidemic activity in type 2 diabetic rats. PMID:19239921

Dewanjee, Saikat; Maiti, Anup; Das, Anup K; Mandal, Subhash C; Dey, Sankar P

2009-06-01

97

The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue  

PubMed Central

Introduction The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. Methods Human breast tissue specimens (malignant n?=?75, normal n?=?15, fibroadenoma n?=?10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RAR?, RAR?), oestrogen (ER?), thyroid hormones (THR?, THR?), and also phosphoinositide-3-kinase (PI3K). Breast cancer cells were treated with Retinoic acid (ATRA), Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression. Results The lowest levels of NIS were detected in normal tissue (Mean(SEM) 0.70(0.12) Log10 Relative Quantity (RQ)) with significantly higher levels observed in fibroadenoma (1.69(0.21) Log10RQ, p<0.005) and malignant breast tissue (1.18(0.07) Log10RQ, p<0.05). Significant positive correlations were observed between human NIS and ER? (r?=?0.22, p<0.05) and RAR? (r?=?0.29, p<0.005), with the strongest relationship observed between NIS and RAR? (r?=?0.38, p<0.0001). An inverse relationship between NIS and PI3K expression was also observed (r?=??0.21, p<0.05). In vitro, ATRA, Estradiol and Thyroxine individually stimulated significant increases in NIS expression (range 6–16 fold), while ATRA and Thyroxine combined caused the greatest increase (range 16–26 fold). Conclusion Although NIS expression is significantly higher in malignant compared to normal breast tissue, the highest level was detected in fibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones. PMID:21283523

Ryan, James; Curran, Catherine E.; Hennessy, Emer; Newell, John; Morris, John C.; Kerin, Michael J.; Dwyer, Roisin M.

2011-01-01

98

Potential of 'flat' fibre evanescent wave spectroscopy to discriminate between normal and malignant cells in vitro.  

PubMed

The present study focuses on evaluating the potential of flattened AgClBr fibre-optic evanescent wave spectroscopy (FTIR-FEWS) technique for detection and identification of cancer cells in vitro using cell culture as a model system. The FTIR-FEWS results are compared to those from FTIR-microspectroscopy (FTIR-MSP) method extensively used to identify spectral properties of intact cells. Ten different samples of control and malignant cells were measured in parallel by the above two methods. Our results show a significant similarity between the results obtained by the two methodologies. The absorbance level of Amide I/Amide II, phosphates and carbohydrates were significantly altered in malignant compared to the normal cells using both systems. Thus, common biomarkers such as Amide I/Amide II, phosphate and carbohydrate levels can be derived to discern between normal and cancer cells. However, marked differences are also noted between the two methodologies in the protein bands due to CH3 bending vibration (1480-1350 cm(-1)). The spectral differences may be attributed to the variation in the penetration depth of the two methodologies. The use of flattened fibre rather than the standard cylindrical fibre has several practical advantages and is considered as an important step towards in vivo measurements in real time, such as that of skin nevi and melanoma using special designs of fibre-optic-based sensors. PMID:17970920

Hammody, Z; Huleihel, M; Salman, A; Argov, S; Moreh, R; Katzir, A; Mordechai, S

2007-11-01

99

Cisplatin in combination with Phenethyl Isothiocyanate (PEITC), a potential new therapeutic strategy for malignant pleural mesothelioma  

PubMed Central

Malignant pleural mesothelioma (MPM) is a very aggressive form of cancer with a poor diagnosis and prognosis. The first line treatment for MPM is a combination of cisplatin and Pemetrexed, which displayed limited efficacy and severe side effects. The naturally occurring compound phenethyl isothiocyanate (PEITC) previously showed interesting anti-tumor properties on several cancer cell lines. We thus aim at evaluating PEITC used alone or in combination with cisplatin in order to improve MPM treatment. Nine MPM cell lines and primary mesothelial cells (PMC), co-cultured or not with M2 macrophages present in MPM microenvironment, were used to assess PEITC and cisplatin anti-tumor properties. Compounds were used alone or in combination. Both PEITC and cisplatin were cytotoxic on MPM cells in a dose dependent manner. We herein showed that PEITC-induced cytotoxicity was due to the generation of reactive oxygen species. Moreover, we showed that cisplatin-PEITC combination allowed the potentialization of both compounds' cytotoxic effects and prevented the emergence of resistant MPM cells. Interestingly, PMC were not sensitive to the combination. Finally, we showed that M2 macrophages did not alter the anti-tumor properties of the combination. Cisplatin-PEITC combination thus represents a promising strategy to induce a selective toxicity towards malignant cells. PMID:25361002

Denis, Iza; Cellerin, Laurent; Gregoire, Marc; Blanquart, Christophe

2014-01-01

100

[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

101

Precancerous lesions of oral mucosa  

PubMed Central

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

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

2014-01-01

102

Soft tissue giant cell tumor of low malignant potential of mediastinum: a rare case report.  

PubMed

Giant cell tumor (GCT) is primarily a bone neoplasm. Rare origin of the tumor from soft tissues has been reported. Involvement of mediastinum by GCT is even rarer. We herein describe an interesting case of huge mediastinal tumor in a young man. Radiologically, no primary osseous lesion was present throughout the body. Morphologically, tumor resembles osseous GCT with increased mitotic activity. Hence, the case was diagnosed as soft tissue GCT of low malignant potential at the rare site of mediastinum. To the best of our knowledge, the present case is the fourth reported case. Pathologists and clinicians need to be aware of the rare diagnosis of GCT in mediastinum and should carefully evaluate the clinical and radiological findings. PMID:24965215

Jain, Deepali; Arava, Sudheer; Mishra, Biplab; Sharma, Sanjay; Sharma, Raju; Parshad, Rajinder

2015-02-01

103

Malignant potential of endometrial stromal tumor with limited infiltration: a case report.  

PubMed

Endometrial stromal tumors (ESTs) with limited infiltration were first proposed by Dionigi et al.(1) However, the prognostic significance of these tumors is unclear. We report a case of a 60-year-old woman who presented with a prolapsed uterine corpus and then underwent laparoscopic-assisted vaginal hysterectomy. A very small EST was incidentally found. The tumor manifested focal irregularity and finger-like permeation into the adjacent myometrium not exceeding 3 mm but exceeding 3 in number, features intermediate between a low-grade endometrial stromal sarcoma and an endometrial stromal nodule. By definition, we rendered a descriptive diagnosis of "endometrial stromal tumor with limited infiltration." A subsequent staging operation confirmed metastasis and, hence, a malignant potential. PMID:24155223

Su, Ting-Fu; Chao, Tai-Kuang; Lee, Herng-Sheng; Perng, Cherng-Lih; Nieh, Shin

2014-09-01

104

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. PMID:24862137

Suryanarayan, Deepa; Schulman, Sam

2014-05-01

105

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

Microsoft Academic Search

Non-melanoma skin cancer is the most frequent type of cancer in humans. In this study we demonstrate that elevated IKK? expression in murine epidermis increases the malignancy potential of skin tumors. We describe the generation of transgenic mice overexpressing IKK? in the basal, proliferative layer of the epidermis and in the outer root sheath of hair follicles. The epidermis of

Josefa P. Alameda; Rodolfo Moreno-Maldonado; M. Jesús Fernández-Aceńero; Manuel Navarro; Angustias Page; José L. Jorcano; Ana Bravo; Ángel Ramírez; M. Llanos Casanova

2011-01-01

106

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. PMID:24194752

Luo, Weihuan; Jiao, Hongbo; Jiang, Chunping

2013-01-01

107

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

PubMed Central

We report two cases of esophagobronchial fistulae diagnosed by Multi-detector computed tomography (MDCT) oral contrast swallow examination. It is helpful to supplement the CT study with an oral contrast swallow as it aids in confirmation of a suspected fistula and also demonstrates the fistula tract better. We present the clinical details and the imaging findings on MDCT of two cases of esophagobronchial fistulae – one secondary to chronic chest tuberculosis and the other secondary to a squamous cell carcinoma of the upper esophagus – followed by discussion of the etiology, pathogenesis, and imaging of these fistulae. PMID:24082484

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

2013-01-01

108

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. PMID:22866098

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

2011-01-01

109

Parafibromin and APC as Screening Markers for Malignant Potential in Atypical Parathyroid Adenomas  

Microsoft Academic Search

The identification of parathyroid carcinomas is based upon histopathological criteria in which an invasive growth pattern\\u000a or distant metastasis is demonstrated. A dilemma arises when tumours present with atypical histopathological features but\\u000a lack direct evidence of malignancy. Recently, reduced expression or loss of the tumour suppressor proteins parafibromin and\\u000a adenomatous polyposis coli (APC) has been associated with parathyroid malignancy. We

C. Christofer Juhlin; Inga-Lena Nilsson; Kenth Johansson; Felix Haglund; Andrea Villablanca; Anders Höög; Catharina Larsson

2010-01-01

110

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. PMID:23629724

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

2013-01-01

111

Preclinical evaluation of bortezomib/dipyridamole novel combination as a potential therapeutic modality for hematologic malignancies.  

PubMed

Novel combinations aiming at maximizing the efficacy of bortezomib are highly valued in the clinic. Therefore the current study investigated the outcomes of combining bortezomib with dipyridamole, a well-known antiplatelet. The co-treatment exerted a synergistic lethality in a panel of human leukemia/lymphoma cell lines of different origin. Mechanistically, dipyridamole did not modulate the proteasome inhibitory activity of bortezomib. However, dipyridamole triggered an endoplasmic reticulum (ER) stress, and co-treatment with bortezomib resulted in higher levels of ER stress than either monotherapies. Relieving ER stress with the protein translation inhibitor, cycloheximide suppressed cell death. Moreover, the enhanced ER stress by the co-treatment was associated with an aggravation of reactive oxygen species (ROS) generation and glutathione (GSH) depletion. Replenishing GSH pools significantly scavenged ROS and rescued the cells. Importantly, the cytotoxicity of the co-treatment was executed mainly via the mitochondrial apoptotic pathway with an efficient suppression of the key anti-apoptotic regulators, Mcl-1, Bcl-xl, Bcl-2 and XIAP, driving the independence of the co-treatment-induced apoptosis of a single apoptotic trigger. Furthermore, the intrinsic potential of bortezomib to inhibit important pro-survival pathways was enhanced by dipyridamole in a GSH/ROS-dependent manner. Interestingly, dipyridamole abrogated JAK2 phosphorylation indirectly and selectively in cancer cells, and the co-treatment-induced cytotoxicity was preserved in a model of stromal-mediated chemoresistance. In nude mice, the antitumor activity of the co-treatment surpassed that of bortezomib monotherapy despite that synergy was lacking. In summary, findings of the present study provided a preclinical rationale which warrants further clinical evaluation of bortezomib/dipyridamole novel combination in hematologic malignancies. PMID:25245324

Goda, Ahmed E; Erikson, Raymond L; Sakai, Toshiyuki; Ahn, Jong-Seog; Kim, Bo-Yeon

2015-01-01

112

Carbohydrate antigens as potential biomarkers for the malignancy in patients with idiopathic deep venous thrombosis: a retrospective cohort study.  

PubMed

A variety of biomarkers have been identified in recent prospective and retrospective reports as being potentially predictive of venous thromboembolis (VTE), particularly idiopathic deep venous thrombosis (IDVT). This study identified a serum tumor biomarker for early screening of IDVT. A total of 128 IDVT patients (54 females and 74 males; average age: 50.9±17.4 years) were included. Carcinoembryonic antigen (CEA), ferritin, ?2-microglobulin, cancer antigen (CA) 125, CA 15-3, CA 19-9, squamous cell carcinoma antigen (SCC), alpha-fetoprotein (AFP), prostate specific antigen (PSA), free PSA (f-PSA), and beta-human chorionic gonadotropin (?-HCG) in patients with IDVT were detected. Malignancies were histo- or cytopathologically confirmed. Of the 128 IDVT patients, 16 (12.5%) were found to have malignancies. Serum CEA, CA 125, CA 15-3, and CA 19-9 were found to be helpful for detecting malignancies in IDVT patients. Our study revealed a positive association between these markers and tumors in IDVT patients. On the other hand, SCC and AFP were not sensitive enough to be markers for detecting tumors in patients with IDVT. No significant differences were found in positive rates of ferritin and ?2-microglobulin between tumor and non-tumor groups, and no significant difference exists in serum levels of ferritin and ?2-microglobulin between the two groups. Carbohydrate antigens, CA 15-3 in particular, may be useful for differential diagnosis and prediction of malignancies in patients with IDVT. PMID:25318883

Yu, Miao; Wang, Yun-Hong; Abdalla, Ahmed M E; Liu, Wen-Qi; Mei, Fei; Wang, Jian; Ouyang, Chen-Xi; Li, Yi-Qing

2014-10-01

113

Recent trends in prevention of oral cancer.  

PubMed

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

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

2014-12-01

114

Recent trends in prevention of oral cancer  

PubMed Central

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

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

2014-01-01

115

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

PubMed Central

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

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

2014-01-01

116

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

PubMed

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

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

2014-01-01

117

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

PubMed

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

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

2005-01-01

118

Malignant Transformation Potentials of Human Umbilical Cord Mesenchymal Stem Cells Both Spontaneously and via 3-Methycholanthrene Induction  

PubMed Central

Human umbilical cord mesenchymal stem cells (HUMSCs) are highly proliferative and can be induced to differentiate into advanced derivatives of all three germ layers. Thus, HUMSCs are considered to be a promising source for cell-targeted therapies and tissue engineering. However there are reports on spontaneous transformation of mesenchymal stem cells (MSCs) derived from human bone marrows. The capacity for HUMSCs to undergo malignant transform spontaneously or via induction by chemical carcinogens is presently unknown. Therefore, we isolated HUMSCs from 10 donors and assessed their transformation potential either spontaneously or by treating them with 3-methycholanthrene (3-MCA), a DNA-damaging carcinogen. The malignant transformation of HUMSCs in vitro was evaluated by morphological changes, proliferation rates, ability to enter cell senescence, the telomerase activity, chromosomal abnormality, and the ability to form tumors in vivo. Our studies showed that HUMSCs from all 10 donors ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUMSCs from two of the 10 donors treated with 3-MCA displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. When these cells (tHUMSCs) were injected into immunodeficient mice, they gave rise to sarcoma-like or poorly differentiated tumors. Moreover, in contrast to HUMSCs, tHUMSCs showed a positive expression of human telomerase reverse transcriptase (hTERT) and did not exhibit a shortening of the relative telomere length during the long-term culture in vitro. Our studies demonstrate that HUMSCs are not susceptible to spontaneous malignant transformation. However, the malignant transformation could be induced by chemical carcinogen 3-MCA. PMID:24339974

Lai, Xiulan; Liu, Sizheng; Chen, Yezeng; Zheng, Zexin; Xie, Qingdong; Maldonado, Martin; Cai, Zhiwei; Qin, Shan; Ho, Guyu; Ma, Lian

2013-01-01

119

The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue  

Microsoft Academic Search

IntroductionThe presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro.MethodsHuman breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR

James Ryan; Catherine E. Curran; Emer Hennessy; John Newell; John C. Morris; Michael J. Kerin; Roisin M. Dwyer; Marian Ludgate

2011-01-01

120

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

PubMed

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

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

2014-11-01

121

From regenerative dentistry to regenerative medicine: progress, challenges, and potential applications of oral stem cells  

PubMed Central

Adult mesenchymal stem cells (MSCs) and epithelial stem cells play essential roles in tissue repair and self-healing. Oral MSCs and epithelial stem cells can be isolated from adult human oral tissues, for example, teeth, periodontal ligament, and gingiva. Cocultivated adult oral epithelial stem cells and MSCs could represent some developmental events, such as epithelial invagination and tubular structure formation, signifying their potentials for tissue regeneration. Oral epithelial stem cells have been used in regenerative medicine over 1 decade. They are able to form a stratified cell sheet under three-dimensional culture conditions. Both experimental and clinical data indicate that the cell sheets can not only safely and effectively reconstruct the damaged cornea in humans, but also repair esophageal ulcer in animal models. Oral MSCs include dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), periodontal ligament stem cells (PDLSCs), and mesenchymal stem cells from gingiva (GMSCs). They are widely applied in both regenerative dentistry and medicine. DPSCs, SHED, and SCAP are able to form dentin–pulp complex when being transplanted into immunodeficient animals. They have been experimentally used for the regeneration of dental pulp, neuron, bone muscle and blood vessels in animal models and have shown promising results. PDLSCs and GMSCs are demonstrated to be ideal cell sources for repairing the damaged tissues of periodontal, muscle, and tendon. Despite the abovementioned applications of oral stem cells, only a few human clinical trials are now underway to use them for the treatment of certain diseases. Since clinical use is the end goal, their true regenerative power and safety need to be further examined. PMID:25506228

Xiao, Li; Nasu, Masanori

2014-01-01

122

A Phase 1 Study of Efatutazone, an Oral Peroxisome Proliferator-Activated Receptor Gamma Agonist, Administered to Patients With Advanced Malignancies  

PubMed Central

BACKGROUND Efatutazone (CS-7017), a novel peroxisome proliferator-activated receptor gamma (PPAR?) agonist, exerts anticancer activity in preclinical models. The authors conducted a phase 1 study to determine the recommended phase 2 dose, safety, tolerability, and pharmacokinetics of efatutazone. METHODS Patients with advanced solid malignancies and no curative therapeutic options were enrolled to receive a given dose of efatutazone, administered orally (PO) twice daily for 6 weeks, in a 3 + 3 intercohort dose-escalation trial. After the third patient, patients with diabetes mellitus were excluded. Efatutazone dosing continued until disease progression or unacceptable toxicity, with measurement of efatutazone pharmacokinetics and plasma adiponectin levels. RESULTS Thirty-one patients received efatutazone at doses ranging from 0.10 to 1.15 mg PO twice daily. Dose escalation stopped when maximal impact on PPAR?-related biomarkers had been reached before any protocol-defined maximum-tolerated dose level. On the basis of a population pharmacokinetic/pharmacodynamic analysis, the recommended phase 2 dose was 0.5 mg PO twice daily. A majority of patients experienced peripheral edema (53.3%), often requiring diuretics. Three episodes of dose-limiting toxicities, related to fluid retention, were noted in the 0.10-, 0.25-, and 1.15-mg cohorts. Of 31 treated patients, 27 were evaluable for response. A sustained partial response (PR; 690 days on therapy) was observed in a patient with myxoid liposarcoma. Ten additional patients had stable disease (SD) for ?60 days. Exposures were approximately dose proportional, and adiponectin levels increased after 4 weeks of treatment at all dose levels. Immunohistochemistry of archived specimens demonstrated that PPAR? and retinoid X receptor expression levels were significantly greater in patients with SD for ?60 days or PR (P = .0079), suggesting a predictive biomarker. CONCLUSIONS Efatutazone demonstrates acceptable tolerability with evidence of disease control in patients with advanced malignancies. PMID:22570147

Pishvaian, Michael J.; Marshall, John L.; Wagner, Andrew J.; Hwang, Jimmy J.; Malik, Shakun; Cotarla, Ion; Deeken, John F.; He, A. Ruth; Daniel, Hirut; Halim, Abdel-Baset; Zahir, Hamim; Copigneaux, Catherine; Liu, Kejian; Beckman, Robert A.; Demetri, George D.

2013-01-01

123

The Malignant Potential of Small Cystic Ovarian Tumors in Women over 50 Years of Age  

Microsoft Academic Search

Objective.The aim of this study was to determine the risk of malignancy in cystic ovarian tumors <10 cm in diameter in asymptomatic postmenopausal women or women ?50 years of age.Methods.All cystic ovarian tumors detected by transvaginal sonography screening in asymptomatic postmenopausal women or women ?50 years of age were evaluated with respect to size and morphology. Histology was recorded on

C. L. Bailey; F. R. Ueland; G. L. Land; P. D. DePriest; H. H. Gallion; R. J. Kryscio; J. R. van Nagell

1998-01-01

124

Rare lymphoid malignancies of the breast: a report of two cases illustrating potential diagnostic pitfalls  

Microsoft Academic Search

Breast involvement by lymphoma is uncommon and poses challenges in diagnosis. Lymphomas may clinically, radiologically, and\\u000a morphologically mimic both benign and neoplastic conditions. We describe two cases of lymphoid malignancies predominantly\\u000a involving the breast, both presenting diagnostic dilemmas. The first case, ALK-negative anaplastic large-cell lymphoma involving\\u000a a seroma associated with a breast implant, is an emerging clinicopathologic entity. Anaplastic large-cell

Evan A. Farkash; Judith A. Ferry; Nancy Lee Harris; Ephraim P. Hochberg; Ronald W. Takvorian; Dan S. Zuckerman; Aliyah R. Sohani

2009-01-01

125

The Internet and the oral healthcare professionals: potential and challenges of a new era.  

PubMed

The Internet is increasingly used as a means of continuous education for healthcare practitioners. At the same time, a rapidly growing number of patients rely on the Internet for the search and acquisition of healthcare-related information and services. This fact has introduced new challenges for the oral healthcare personnel, which must not only often face the misperceptions of ill-informed patients but also be able to redirect them to quality sources of healthcare-related information. Consequently, there is a great need for the whole oral healthcare team to further understand the potential and dangers of Internet-based information. The present paper aimed to briefly discuss the major implications of Internet use from two distinct points of view: (a) potential and risks of Internet use for lifelong learning and quality assessment of the oral healthcare team and (b) potential and dangers from the Internet as a means of patients' education. (1) generic Internet search; (2) search within healthcare-related databases; and (3) principles quality assessment of information and resources. PMID:17615024

Mattheos, N

2007-08-01

126

Oral and transdermal dl-methylphenidate – ethanol interactions in C57BL/6J mice: Potentiation of locomotor activity with oral delivery  

PubMed Central

Purpose Many abusers of dl-methylphenidate co-abuse ethanol. The present animal study examined behavioral effects of oral or transdermal dl-methylphenidate in combination with a high, depressive dose of ethanol to model co-abuse. Methods Locomotor activity of C57BL/6J mice was recorded for 3 h following dosing with either oral dl-methylphenidate (7.5 mg/kg) or transdermal dl-methylphenidate (Daytrana®;Ľ of a 12.5 cm2 patch; mean dose 7.5 mg/kg), with or without oral ethanol (3 g/kg). Brains were enantiospecifically analyzed for the isomers of methylphenidate and the transesterification metabolite ethylphenidate. Results An otherwise depressive dose of ethanol significantly potentiated oral dl-methylphenidate induced increases in total distance traveled for the first 100 min (p<0.05). Transdermal dl-methylphenidate increased total distance traveled after a latency of 80 min, though this effect was not potentiated by concomitant ethanol. Mean 3 h brain d-methylphenidate concentrations were significantly elevated by ethanol in both the oral (65% increase) and transdermal (88% increase) groups. The corresponding l-ethylphenidate concentrations were 10 ng/g and 130 ng/g. Conclusions Stimulant induced motor activity in rodents may correlate with abuse liability. Potentiation of dl-methylphenidate motor effects by concomitant ethanol carries implications regarding increased abuse potential of dl-methylphenidate when combined with ethanol. PMID:21925201

Bell, Guinevere H.; Griffin, William C.; Patrick, Kennerly S.

2011-01-01

127

The human immunodeficiency virus protease inhibitor ritonavir is potentially active against urological malignancies  

PubMed Central

The human immunodeficiency virus protease inhibitor ritonavir has recently been shown to have antineoplastic activity, and its use in urological malignancies is under investigation with an eye toward drug repositioning. Ritonavir is thought to exert its antineoplastic activity by inhibiting multiple signaling pathways, including the Akt and nuclear factor-kappaB pathways. It can increase the amount of unfolded proteins in the cell by inhibiting both the proteasome and heat shock protein 90. Combinations of ritonavir with agents that increase the amount of unfolded proteins, such as proteasome inhibitors, histone deacetylase inhibitors, or heat shock protein 90 inhibitors, therefore, induce endoplasmic reticulum stress cooperatively and thereby kill cancer cells effectively. Ritonavir is also a potent cytochrome P450 3A4 and P-glycoprotein inhibitor, increasing the intracellular concentration of combined drugs by inhibiting their degradation and efflux from cancer cells and thereby enhancing their antineoplastic activity. Furthermore, riotnavir’s antineoplastic activity includes modulation of immune system activity. Therapies using ritonavir are thus an attractive new approach to cancer treatment and, due to their novel mechanisms of action, are expected to be effective against malignancies that are refractory to current treatment strategies. Further investigations using ritonavir are expected to find new uses for clinically available drugs in the treatment of urological malignancies as well as many other types of cancer.

Sato, Akinori

2015-01-01

128

Perspective and potential of oral lipid-based delivery to optimize pharmacological therapies against cardiovascular diseases.  

PubMed

Cardiovascular diseases (CVDs) remain the major cause of morbidity and mortality globally. Despite the large number of cardiovascular drugs available for pharmacological therapies, factors limiting the efficient oral use are identified, including low water solubility, pre-systemic metabolism, food intake effects and short half-life. Numerous in vivo proof-of-concepts studies are presented to highlight the viability of lipid-based delivery to optimize the oral delivery of cardiovascular drugs. In particular, the key performance enhancement roles of oral lipid-based drug delivery systems (LBDDSs) are identified, which include i) improving the oral bioavailability, ii) sustaining/controlling drug release, iii) improving drug stability, iv) reducing food intake effect, v) targeting to injured sites, and vi) potential for combination therapy. Mechanisms involved in achieving these features, range of applicability, and limits of available systems are detailed. Future research and development efforts to address these issues are discussed, which is of significant value in directing future research work in fostering translation of lipid-based formulations into clinical applications to reduce the prevalence of CVDs. PMID:24852093

Rao, Shasha; Tan, Angel; Thomas, Nicky; Prestidge, Clive A

2014-11-10

129

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

PubMed

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

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

2013-06-01

130

P36. The prognostic potential of circulating and tissue activin A level in malignant pleural mesothelioma  

PubMed Central

Background Malignant pleural mesothelioma (MPM) is an aggressive malignancy characterized by poor outcome and there is a lack of prognostic biomarkers to estimate prognosis. Previously we have shown that suppression of activin A can interfere with MPM tumor growth. In the current study, we compare the circulating and tissue expression level of activin A as a prognostic biomarker in MPM. Methods In a cohort of 53 MPM patients, plasma samples were collected between 2010 and 2014. Controls consisted of age-matched healthy individuals (n=46) and patients with pleuritis or pleural fibrosis (n=16). Circulating activin A was measured by ELISA and correlated to clinicopathological data. Furthermore, activin A expression in the tumor tissue was semiquantitatively measured by immunohistochemistry in 24 patients. Results Plasma activin A level was significantly elevated in MPM patients (n=53, 843±122 pg/mL) when compared to healthy controls (452±144 pg/mL, P=0.0039). Non-malignant pleuritis or pleural fibrosis patients only showed a modest, non-significant increase (625±95 pg/mL, P=0.093). Circulating activin A levels were slightly increased in cases with non-epitheloid morphology (n=16, 1101±183) when compared to epithelioid (n=37, 732±153 pg/mL, P=0.13). MPM patients with below median activin A concentrations had a modestly and non-significantly longer overall survival when compared to the high activin A level patients (469 vs. 271 days, P=0.4751). Interestingly, there was no correlation between circulating and tissue expression level of activin A in 17 patients where both parameters could have been analyzed. Conclusions Our findings suggest that the measurement of circulating activin A may support the diagnosis and prognosis of MPM but additional patient cohorts need to be analyzed to establish the diagnostic and prognostic value of this non-invasive biomarker.

Dong, Yawen; Hoda, Mir Alireza; Schelch, Karin; Rozsas, Anita; Laszlo, Viktoria; Dome, Balazs; Grusch, Michael; Berger, Walter; Klepetko, Walter; Hegedus, Balazs

2014-01-01

131

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. PMID:23857227

Iriti, Marcello; Varoni, Elena Maria

2013-01-01

132

Tumor-targeting bacterial therapy: A potential treatment for oral cancer (Review)  

PubMed Central

Certain obligate or facultative anaerobic bacteria, which exhibit an inherent ability to colonize solid tumors in vivo, may be used in tumor targeting. As genetically manipulated bacteria may actively and specifically penetrate into the tumor tissue, bacterial therapy is becoming a promising approach in the treatment of tumors. However, to the best of our knowledge, no reports have been published thus far regarding the bacterial treatment of oral cancer, one of the most common types of cancer worldwide. In this review, the progress in the understanding of bacterial strategies used in tumor-targeted therapy is discussed and particular bacterial strains that may have great therapeutic potential in oral squamous cell carcinoma (OSCC) tumor-targeted therapy are predicted as determined by previous studies. PMID:25364397

LIU, SAI; XU, XIAOPING; ZENG, XIN; LI, LONGJIANG; CHEN, QIANMING; LI, JING

2014-01-01

133

Tumor-targeting bacterial therapy: A potential treatment for oral cancer (Review).  

PubMed

Certain obligate or facultative anaerobic bacteria, which exhibit an inherent ability to colonize solid tumors in vivo, may be used in tumor targeting. As genetically manipulated bacteria may actively and specifically penetrate into the tumor tissue, bacterial therapy is becoming a promising approach in the treatment of tumors. However, to the best of our knowledge, no reports have been published thus far regarding the bacterial treatment of oral cancer, one of the most common types of cancer worldwide. In this review, the progress in the understanding of bacterial strategies used in tumor-targeted therapy is discussed and particular bacterial strains that may have great therapeutic potential in oral squamous cell carcinoma (OSCC) tumor-targeted therapy are predicted as determined by previous studies. PMID:25364397

Liu, Sai; Xu, Xiaoping; Zeng, Xin; Li, Longjiang; Chen, Qianming; Li, Jing

2014-12-01

134

Critical analysis of the potential for targeting STAT3 in human malignancy  

PubMed Central

The signal transducer and activator of transcription (STAT) family of proteins was originally discovered in the context of normal cell biology where they function to transduce intracellular and extracellular signals to the nucleus, ultimately leading to transcription of specific target genes and downstream phenotypic effects. It was quickly appreciated that the STATs, especially STAT3, play a fundamental role in human malignancy. In contrast to normal biology in which transient STAT3 signaling is strictly regulated by a tightly coordinated network of activators and deactivators, STAT3 is constitutively activated in human malignancies. Constitutive STAT3 signaling has been associated with many cancerous phenotypes across nearly all human cancers, including the upregulation of cell growth, proliferation, survival, and motility, among others. Studies involving candidate preclinical STAT3 inhibitors have further demonstrated that the reversal of these phenotypes results from pharmacologic or genetic inhibition of STAT3, suggesting that STAT3 may be a promising target for clinical interventions. Indeed, a Phase 0 clinical trial involving a STAT3 decoy oligonucleotide demonstrated that STAT3 is a drug-gable target in human tumors. Because of the ubiquity of overactive STAT3 in cancer, its role in promoting a wide variety of cancerous phenotypes, and the strong clinical and preclinical studies performed to date, STAT3 represents a promising target for the development of inhibitors for the treatment of human cancers. PMID:23935373

Peyser, Noah D; Grandis, Jennifer R

2013-01-01

135

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. PMID:24204145

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

2013-01-01

136

Oral calcitonin  

PubMed Central

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

Hamdy, Ronald C; Daley, Dane N

2012-01-01

137

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. PMID:23922786

Mravak-Stipeti?, Marinka; Sabol, Ivan; Kranj?i?, Josip; Kneževi?, Marjana; Grce, Magdalena

2013-01-01

138

Oral Lichen Planus as a Preneoplastic Inflammatory Model  

PubMed Central

Oral lichen planus (OLP) is a chronic oral inflammatory disease of unknown etiology. According to reports, 1-2% of OLP patients develop oral squamous cell carcinoma (OSCC) in the long run. While World Health Organization (WHO) classifies OLP as “a potentially malignant disorder,” it is still a matter of debate which mechanisms drive OLP to such a condition. The current hypothesis connecting OLP and OSCC is that chronic inflammation results in crucial DNA damage which over time results in cancer development. Initial studies investigating the OLP and OSCC link were mainly retrospective clinical studies. Over the past years, several amount of information has accumulated, mainly from molecular studies on the OLP malignant potential. This article is a critical review of whether OLP has a malignant potential and, therefore, represents a model of preneoplastic inflammation. PMID:22675259

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

2012-01-01

139

Oral lichen planus as a preneoplastic inflammatory model.  

PubMed

Oral lichen planus (OLP) is a chronic oral inflammatory disease of unknown etiology. According to reports, 1-2% of OLP patients develop oral squamous cell carcinoma (OSCC) in the long run. While World Health Organization (WHO) classifies OLP as "a potentially malignant disorder," it is still a matter of debate which mechanisms drive OLP to such a condition. The current hypothesis connecting OLP and OSCC is that chronic inflammation results in crucial DNA damage which over time results in cancer development. Initial studies investigating the OLP and OSCC link were mainly retrospective clinical studies. Over the past years, several amount of information has accumulated, mainly from molecular studies on the OLP malignant potential. This article is a critical review of whether OLP has a malignant potential and, therefore, represents a model of preneoplastic inflammation. PMID:22675259

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

2012-01-01

140

Oral medicine and the ageing population.  

PubMed

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

Yap, T; McCullough, M

2015-03-01

141

Enantioselective oral bioavailability of 0-isovaleryl propranolol as a potential prodrug of propranolol.  

PubMed

The enantioselective oral bioavailability of propranolol (PL) from 0-isovaleryl-PL was determined and compared with parent PL in beagle dogs. The bioavailability of the individual enantiomer from the prodrug increased about 2 fold. The AUC ratio between the S(-)- and R(+)-isomer posed at 0.89 which was statistically not different from that obtained after administration of PL alone. These features indicate that 0-isovaleryl-PL promises to be a potential prodrug of PL from the pharmacokinetic and pharmacodynamic point of view. PMID:1287187

Shameem, M; Imai, T; Otagiri, M

1992-09-01

142

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

143

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. PMID:24648944

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

144

Preclinical evidence of potential craniofacial adverse effect of zoledronic acid in pediatric patients with bone malignancies.  

PubMed

High doses of zoledronic acid (ZOL), one of the most potent inhibitors of bone resorption, are currently evaluated in phase III clinical trials in Europe for the treatment of malignant pediatric primary bone tumors. The impact of such an intensive treatment on the craniofacial skeleton growth is a critical question in the context of patients with actively growing skeleton; in particular, in light of our previous studies evidencing that endochondral bone formation was transiently disturbed by high doses of ZOL. Two protocols adapted from pediatric treatments were developed for newborn mice (a total of 5 or 10 injections of ZOL 50?g/kg every two days). Their impact on skull bones and teeth growth was analyzed by X-rays, microCT and histology up to 3months after the last injection. ZOL administrations induced a transient delay of skull bone growth and an irreversible delay in incisor, first molar eruption and root elongation. Other teeth were affected, but most were erupted by 3months. Root histogenesis was severely impacted for all molars and massive odontogenic tumor-like structures were observed in all mandibular incisors. High doses of ZOL irreversibly disturbed teeth eruption and elongation, and delayed skull bone formation. These preclinical observations are essential for the follow-up of onco-pediatric patients treated with ZOL. PMID:25193159

Lézot, Frédéric; Chesneau, Julie; Battaglia, Séverine; Brion, Régis; Castaneda, Beatriz; Farges, Jean-Christophe; Heymann, Dominique; Rédini, Françoise

2014-11-01

145

Improved oral therapeutic potential of nanoencapsulated cryptdin formulation against Salmonella infection.  

PubMed

An encapsulated system for cryptdin-2 (a Paneth cell antimicrobial peptide) was developed, with a view to help it sustain adverse gut conditions and to ensure its bioavailability on oral administration. The formulation was characterized on the basis of particle size, zeta potential and polydispersity index. Cryptdin-2 loaded nanoparticles of size 105±7nm, formulated by ionotropic gelation method using chitosan: tripolyphosphate (5:2), revealed 60% drug entrapment efficiency with 65% in vitro release in 4.5h. Developed system was evaluated for its therapeutic application against Salmonella Typhimurium infection in mice, on the basis of survivability of animals, bacterial load in tissues, histo-architecture and oxidative damage markers. Infected mice when treated with the encapsulated peptide showed 83% survivability and approximately 2 log unit reductions in the bacterial load in the tissues versus 100% mortality observed with the free peptide. The encapsulated cryptdin-2 also achieved a decrease in the level of oxidants, particularly nitrite by 3.25 folds and increased the level of antioxidant catalase by 2 folds when compared to the levels exhibited by the free peptide. The bacteriological and biochemical alterations illustrated by encapsulated peptide co-related well with the histo-architectural studies. The study is a first pre-clinical report on the oral effectiveness of cryptdin-2 by its suitable encapsulation and has potential for future clinical applications. PMID:25724130

Rishi, Praveen; Bhogal, Akanksha; Arora, Sumeha; Pandey, Satish K; Verma, Indu; Kaur, Indu Pal

2015-05-25

146

Analysis of potential oral cleft risk factors in the Kosovo population.  

PubMed

The aim of this study was to analyze the association of potential risk factors such as positive family cleft history, smoking, use of drugs during pregnancy, and parental age with oral clefts in offspring within the Kosovo population. We conducted a population-based case-control study of live births in Kosovo from 1996 to 2005. Using a logistic regression model, 244 oral cleft cases were compared with 488 controls. We have excluded all syndromic clefts. Heredity increases the risk of clefts in newborns [odds ratio (OR) = 8.25, 95% confidence interval (CI) 3.12-23.52]. Clefts were also associated with smoking (OR = 1.87, 95% CI 0.75-4.08), use of drugs during pregnancy (OR = 2.25, 95% CI 0.82-5.12), increasing maternal age (OR = 1.83, 95% CI 1.42-2.49), and increasing paternal age (OR = 1.3, 95% CI 1.2- 1.4). We found heredity to be the most important factor for cleft occurrence in Kosovar newborns. Another significant potential risk factor for occurrence of clefts is the parental age. We found the use of drugs and smoking during pregnancy to be less significant. PMID:24670027

Salihu, Sami; Krasniqi, Blerim; Sejfija, Osman; Heta, Nijazi; Salihaj, Nderim; Geci, Agreta; Sejdini, Milaim; Arifi, Hysni; Isufi, Ramazan; Ueeck, Brett A

2014-01-01

147

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

PubMed

This paper reports the content in macronutrients, free sugars, polyphenols, and inorganic ions, known to exert any positive or negative action on microbial oral disease such as caries and gingivitis, of seven food/beverages (red chicory, mushroom, raspberry, green and black tea, cranberry juice, dark beer). Tea leaves resulted the richest material in all the detected ions, anyway tea beverages resulted the richest just in fluoride. The highest content in zinc was in chicory, raspberry and mushroom. Raspberry is the richest food in strontium and boron, beer in selenium, raspberry and mushroom in copper. Beer, cranberry juice and, especially green and black tea are very rich in polyphenols, confirming these beverages as important sources of such healthy substances. The fractionation, carried out on the basis of the molecular mass (MM), of the water soluble components occurring in raspberry, chicory, and mushroom extracts (which in microbiological assays revealed the highest potential action against oral pathogens), showed that both the high and low MM fractions are active, with the low MM fractions displaying the highest potential action for all the fractionated extracts. Our findings show that more compounds that can play a different active role occur in these foods. PMID:22013381

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

2011-01-01

148

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. PMID:22013381

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

2011-01-01

149

Mucinous cystic neoplasms of the pancreas: are we overestimating malignant potential?  

PubMed

Surgical resection is recommended for all mucinous cystic neoplasms (MCNs) of the pancreas as a result of: 1) lack of an accurate tumor marker for invasive cancer; 2) young age at diagnosis; and 3) historical studies revealing 36 per cent incidence of malignancy in resected lesions. This study compares the clinicopathologic and prognostic features of our series of resected MCNs to recent studies using the current International Association of Pancreatology (IAP) system. Thirty-eight resected MCNs were identified. Almost all patients were female (97.4%); median age at diagnosis was 53.5 years (interquartile range [IQR], 41.3 to 61.0). The majority occurred in the body/tail of the pancreas (86.8%); median size on computed tomography/magnetic resonance imaging was 5.0 cm (IQR, 3 to 8.8). Comparison of the five high-grade (HG, 13.2%) and 33 low-grade (86.8%) MCNs revealed that 1) patients were similar in age (55.0 vs 52.0 years, respectively) and 2) HG lesions were significantly larger on preoperative imaging (9.9 vs 3.5 cm) and final pathology (10.9 vs 3.5 cm). These data, taken together with five recent studies that adhere to the 2012 IAP criteria (385 total MCNs), reveal that a cutoff of less than 3 cm without mural nodules would have only missed one (0.26%) HG lesion. Surveillance of these lesions may be appropriate for some patients. PMID:25264629

Nguyen, David; Dawson, David W; Hines, O Joe; Reber, Howard A; Donahue, Timothy R

2014-10-01

150

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

PubMed

Omega-3 fatty acids (also called ?-3 fatty acis or n-3 fatty acid) are polyunsaturated fatty acids (PUFAs) with a double bond (C=C) at the third carbon atom from the end of the carbon chain. Numerous test tube and animal studies have shown that omega-3 fatty acids may prevent or inhibit the growth of cancers, suggesting that omega-3 fatty acids are important in cancer physiology. Alpha-linolenic acid (ALA) is one of an essential omega-3 fatty acid and organic compound found in seeds (chia and flaxseed), nuts (notably walnuts), and many common vegetable oils. ALA has also been shown to down-regulate cell proliferation of prostate, breast, and bladder cancer cells. However, direct evidence that ALA suppresses to the development of colon cancer has not been studied. Also, no previous studies have evaluated whether ALA may regulate malignant potential (adhesion, invasion and colony formation) in colon cancer cells. In order to address the questions above, we conducted in vitro studies and evaluated whether ALA may down-regulate malignant potential in human (HT29 and HCT116) and mouse (MCA38) colon cancer cell lines. We observed that treatment with 1-5 mM of ALA inhibits cell proliferation, adhesion and invasion in both human and mouse colon cancer cell lines. Interestingly, we observed that ALA did not decrease total colony numbers when compared to control. By contrast, we found that size of colony was significantly changed by ALA treatment when compared to control in all colon cancer cell lines. We suggest that our data enhance our current knowledge of ALA's mechanism and provide crucial information to further the development of new therapies for the management or chemoprevention of colon cancer. PMID:25336096

Chamberland, John P; Moon, Hyun-Seuk

2015-03-01

151

Chemokines and Cytokines as Salivary Biomarkers for the Early Diagnosis of Oral Cancer  

PubMed Central

Chemokines have been shown to be important in both inflammation and carcinogenesis and are able to be measured in saliva with relatively robust methods including enzyme-linked immunosorbent assays (ELISA). Thus it has been hypothesized that patients with oral cancer and oral potentially malignant lesions will have elevated levels of specific chemokines in oral fluids and that this may be used as a marker of both the early detection of malignant disease and progression to malignancy. The concept that salivary biomarkers can be easily measured and indicate disease states has profound consequences for clinical practice and may open up new strategies for the diagnosis, prognosis, and potential therapy of oral squamous cell carcinoma (OSCC). This review focuses on our understanding of cytokines and chemokines and the potential role that they may have in clinical practice. PMID:24376459

Prasad, Gareema; McCullough, Michael

2013-01-01

152

Anti-Heparanase Aptamers as Potential Diagnostic and Therapeutic Agents for Oral Cancer  

PubMed Central

Heparanase is an endoglycosidase enzyme present in activated leucocytes, mast cells, placental tissue, neutrophils and macrophages, and is involved in tumour metastasis and tissue invasion. It presents a potential target for cancer therapies and various molecules have been developed in an attempt to inhibit the enzymatic action of heparanase. In an attempt to develop a novel therapeutic with an associated diagnostic assay, we have previously described high affinity aptamers selected against heparanase. In this work, we demonstrated that these anti-heparanase aptamers are capable of inhibiting tissue invasion of tumour cells associated with oral cancer and verified that such inhibition is due to inhibition of the enzyme and not due to other potentially cytotoxic effects of the aptamers. Furthermore, we have identified a short 30 bases aptamer as a potential candidate for further studies, as this showed a higher ability to inhibit tissue invasion than its longer counterpart, as well as a reduced potential for complex formation with other non-specific serum proteins. Finally, the aptamer was found to be stable and therefore suitable for use in human models, as it showed no degradation in the presence of human serum, making it a potential candidate for both diagnostic and therapeutic use. PMID:25295847

Silva, Dilson; Cortez, Celia M.; McKenzie, Edward A.; Bitu, Carolina C.; Salo, Sirpa; Nurmenniemi, Sini; Nyberg, Pia; Risteli, Juha; deAlmeida, Carlos E. B.; Brenchley, Paul E. C.; Salo, Tuula; Missailidis, Sotiris

2014-01-01

153

Primary malignant melanoma of maxillary gingiva.  

PubMed

Malignant melanoma of maxillary gingiva is a rare clinical entity. Mucosal melanoma is more aggressive than cutaneous form and carries comparatively poorer prognosis. High index of suspicion is required for diagnosing malignant melanoma of oral cavity. Any pigmented lesion in the oral cavity should be taken seriously by the clinician. PMID:25177127

Thakur, Sudhir Kumar; Jha, Somen; Singh, Sarabjeet; Yadav, Anubha

2014-06-01

154

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. PMID:22719872

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

2012-01-01

155

Asteropsins B–D, sponge-derived knottins with potential utility as a novel scaffold for oral peptide drugs  

PubMed Central

Background Known linear knottins are unsuitable as scaffolds for oral peptide drug due to their gastrointestinal instability. Herein, a new subclass of knottin peptides from Porifera is structurally described and characterized regarding their potential for oral peptide drug development. Methods Asteropsins B–D (ASPB, ASPC, and ASPD) were isolated from the marine sponge Asteropus sp. The tertiary structures of ASPB and ASPC were determined by solution NMR spectroscopy and that of ASPD by homology modeling. Results The isolated asteropsins B–D, together with the previously reported asteropsin A (ASPA), compose a new subclass of knottins that share a highly conserved structural framework and remarkable stability against the enzymes in gastrointestinal tract (chymotrypsin, elastase, pepsin, and trypsin) and human plasma. Conclusion Asteropsins can be considered as promising peptide scaffolds for oral bioavailability. General significance The structural details of asteropsins provide essential information for the engineering of orally bioavailable peptides. PMID:24225326

Li, Huayue; Bowling, John J.; Su, Mingzhi; Hong, Jongki; Lee, Bong-Jin; Hamann, Mark T.; Jung, Jee H.

2014-01-01

156

Potential Bias due to Excluding Oral Contraceptive Users When Estimating Menstrual Cycle Characteristics  

Microsoft Academic Search

Women take oral contraceptives for contraception but also for menstrual dysfunction treatment. This raises the question of whether or not women with menstrual dysfunction are underrepresented in analyses of menstrual function because oral contraceptive users are excluded. To explore this, the authors examined the history of oral contraceptive use among 1,322 Black women and White women, aged 35-49 years, who

Ganesa Wegienka; Donna Day Baird

157

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

Microsoft Academic Search

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

Hendree E. Jones; Roland R. Griffiths

2003-01-01

158

Danazol-beta-cyclodextrin binary system: a potential application in emergency contraception by the oral route.  

PubMed

This study explored the potential of beta-cyclodextrin to improve the aqueous solubility and dissolution of danazol, investigated a simple and less expensive method for preparation of a danazol-beta-cyclodextrin binary system, and explored the potential application of a danazol-beta-cyclodextrin binary system as a single-dose emergency contraceptive. Phase solubility analysis indicated formation of a first-order soluble complex with stability constant 972.03 M(-1), while Job's plot affirmed 1:1 stoichiometry. The hyperchromic shift in the UV-Vis spectrum of danazol in the presence of beta-cyclodextrin indicated solubilization capability of beta-cyclodextrin for danazol. The extrinsic Cotton effect with a negative peak at 280.7 nm confirmed the inclusion of danazol in the asymmetric locus of beta-cyclodextrin. (1)H-nuclear magnetic resonance analysis suggested that the protons of the steroidal skeleton of danazol display favorable interactions with the beta-cyclodextrin cavity. The danazol-beta-cyclodextrin binary system was prepared by kneading, solution, freeze-drying, and milling methods. The extent of the enhancement of dissolution rate was found to be dependent on the preparation method. Dissolution studies showed a similar relative dissolution rate (2.85) of the danazol-beta-cyclodextrin binary system prepared by the freeze-drying and milling (in the presence of 13% moisture) methods. In a mouse model, the danazol-beta-cyclodextrin binary system at 51.2 mg/kg (equivalent to a 400-mg human dose) showed 100% inhibition of implantation when given postcoitally. Moreover, the danazol-beta-cyclodextrin binary system is safe up to 2000 mg/kg in the mouse (15.52 g/70 kg human) as a single oral dose. Thus, the danazol-beta-cyclodextrin binary system could serve as a new therapeutic application: an oral emergency contraceptive at a physiologically acceptable single dose. PMID:17622113

Jadhav, Ganesh S; Vavia, Pradeep R; Nandedkar, Tarala D

2007-01-01

159

Areca nut and its role in oral submucous fibrosis.  

PubMed

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

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

2014-12-01

160

Areca nut and its role in oral submucous fibrosis  

PubMed Central

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

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

2014-01-01

161

Complex mucinous cystadenoma of undetermined malignant potential of the urachus: a rare case with review of the literature.  

PubMed

Urachal carcinoma is an uncommon neoplasm. Benign urachal tumours are extremely rare. All urachal mucinous tumours, regardless of tumour type, have the potential to behave in an aggressive clinical manner that includes the development of pseudomyxoma peritonei. We report a 58-year-old man who presented with lower abdominal pain. Ultrasound and CT imaging defined a large lobulated cystic mass superior to the urinary bladder. At laparotomy, the multiloculated cystic mass, 10 x 8 x 6 cm, could be completely separated from the bladder and was excised. It was smooth-walled and filled with thick mucinous fluid. Histology revealed a complex mucinous cystadenoma of undetermined malignant potential of the urachus. The cystic spaces were lined by mucin-secreting columnar epithelium that showed focal areas of mild atypia. The epithelium lacked architectural features of villous adenoma. There was no stromal invasion to support an invasive neoplastic process. No pseudomyxoma peritonei was present. The patient was well, with no tumour recurrence, at 6 months follow-up. PMID:25194538

Prakash, Malur R; Vijayalaxmi, Suranagi V; Maitreyee, Roy; Ranjit, Kangle P

2014-08-01

162

Oral Direct Renin Inhibition: Premise, Promise, and Potential Limitations of a New Class of Antihypertensive Drug  

PubMed Central

The first oral direct renin inhibitor, aliskiren, recently received approval for the treatment of hypertension. This article addresses the premise, promise, and potential limitations of this new class of renin-angiotensin system inhibitor. While aliskiren adds to a list of > 100 drugs approved for the treatment of hypertension, its introduction into clinical medicine is of particular interest because of the novel mechanism of action— inhibition of renin’s catalytic activity, the most proximal and rate-limiting step in renin-angiotensin system activation. By producing more complete renin-angiotensin system inhibition than with existing agents, direct renin inhibitors may afford greater protection from hypertensive complications. Other potential advantages include additional blood pressure reduction when used in combination therapy, a placebo-like side-effect profile, avid renal concentration, and long duration of action. Potential limitations include modest levels of blood pressure reduction that are equivalent to but not greater than angiotensin receptor blockers, reduced gastrointestinal absorption with a high fat meal, and large reactive increases in renin secretion—the functional importance of which is under intense investigation. The results of outcomes trials are eagerly awaited. PMID:18374681

Shafiq, Moiz M.; Menon, Dileep V.; Victor, Ronald G.

2008-01-01

163

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

PubMed Central

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

Bennett, Michael; Mashimo, Hiroshi

2014-01-01

164

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

SciTech Connect

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

Capala, J.; Barth, R.F.; Adams, D.M.; Bailey, M.Q.; Soloway, A.H. [Ohio State Univ., Columbus, OH (United States); Carlsson, J. [Uppsala Univ. (Sweden). Dept. of Radiation Sciences

1994-12-31

165

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

Microsoft Academic Search

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

Enzo A. Palombo

2009-01-01

166

Bevacizumab for the Treatment of Non-Resectable Pseudomyxoma peritonei Associated with Mucinous Ovarian Tumor of Low Malignant Potential – A Comparison of Two Cases  

Microsoft Academic Search

Pseudomyxoma peritonei (PMP) is a rare tumor syndrome that can be diagnosed in association with mucinous ovarian tumors of low malignant potential. Surgical debulking is the primary treatment modality as chemotherapy has generally proven ineffective in this slowly progressive tumor. When patients with PMP are not surgical candidates, there is no effective treatment, and patients will die of progressive disease.We

Ira Winer; Ronald J. Buckanovich

2010-01-01

167

[Frontiers in Bioscience 11, 1508-1521, May 1, 2006] Posttranslational modifications of Bcl2 family members-a potential therapeutic target for human malignancy  

E-print Network

immunotherapy utilizes the body's immune system either directly or indirectly to boost body's cancer fighting family members-a potential therapeutic target for human malignancy Aruna Basu 1 Garrett DuBois 2 feature of all known human cancers-the ability to influence their onset, progression and outcome. Bcl2

168

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

PubMed Central

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

Aalipour, Amin

2014-01-01

169

MK-4815, a Potential New Oral Agent for Treatment of Malaria  

PubMed Central

Malaria continues to have a significant impact on the health of the developing world. Efforts to combat this disease now focus on combination therapy in order to stem the emergence of resistant parasites. Continued efforts are needed to discover and develop new agents for use in combination antimalarial regimens. MK-4815 is a small molecule with antimalarial activity that was identified from a large pharmaceutical compound collection using a semiautomated version of a well-established in vitro assay for the erythrocytic stages of Plasmodium falciparum. In vitro studies indicate that the compound selectively accumulates in infected red blood cells and is most effective against the metabolically active late trophozoite/early schizont stages. A variety of drug-resistant field isolates of P. falciparum were found to be as sensitive to MK-4815 as the wild-type lines. MK-4815 is orally active in a P. berghei mouse model of acute malaria. In this model, where untreated animals succumb to infection 10 to 12 days postinfection, MK-4815 was completely curative when given as a single dose of 50 mg/kg, 2 doses of 25 mg/kg, or 4.5 doses of 12.5 mg/kg. In pharmacokinetic studies with mice and rhesus monkeys, MK-4815 demonstrated oral bioavailability and low clearance. In addition, MK-4815 is inexpensive to synthesize, an important characteristic for providing affordable antimalaria therapy to the developing world. The attractive biological and pharmaceutical profile of MK-4815 demonstrates its potential for use in combination with other agents in the fight against malaria. PMID:22314528

Allocco, John; Yeung, Lai; Nare, Bakela; Liberator, Paul; Schmatz, Dennis

2012-01-01

170

Benefit cost scenarios of potential oral rabies vaccination for skunks in California.  

PubMed

Scenario-based analyses were computed for benefits and costs linked with hypothetical oral rabies vaccination (ORV) campaigns to contain or eliminate skunk-variant rabies in skunks (Mephitis mephitis) in California, USA. Scenario 1 assumed baiting eight zones (43,388 km(2) total) that comprised 73% of known skunk rabies locations in the state. Scenario 2 also assumed baiting these eight zones, but further assumed that added benefits would result from preventing the spread of skunk-variant rabies into Los Angeles County, USA. Scenarios assumed a fixed bait cost ($1.24 each) but varied campaigns (one, two and three annual ORV applications), densities of baits (37.5/km(2), 75/km(2) and 150/km(2)), levels of prevention (50%, 75%, and 100%), and contingency expenditures if rabies recurred (20%, 40%, and 60% of campaign costs). Prorating potential annual benefits during a 12-yr time horizon yielded benefit-cost ratios (BCRs) between 0.16 and 2.91 and between 0.34 and 6.35 for Scenarios 1 and 2, respectively. Economic issues relevant to potentially managing skunk-variant rabies with ORV are discussed. PMID:19204355

Shwiff, Stephanie A; Sterner, Ray T; Hale, Robert; Jay, Michele T; Sun, Ben; Slate, Dennis

2009-01-01

171

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

Microsoft Academic Search

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

Shu Abe; Kazuyuki Ishihara; Katsuji Okuda

2001-01-01

172

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 ...

173

Luteolin reduces the invasive potential of malignant melanoma cells by targeting ?3 integrin and the epithelial-mesenchymal transition  

PubMed Central

Aim: To investigate whether luteolin, a highly prevalent flavonoid, reverses the effects of epithelial-mesenchymal transition (EMT) in vitro and in vivo and to determine the mechanisms underlying this reversal. Methods: Murine malignant melanoma B16F10 cells were exposed to 1% O2 for 24 h. Cellular mobility and adhesion were assessed using Boyden chamber transwell assay and cell adhesion assay, respectively. EMT-related proteins, such as E-cadherin and N-cadherin, were examined using Western blotting. Female C57BL/6 mice (6 to 8 weeks old) were injected with B16F10 cells (1×106 cells in 0.2 mL per mouse) via the lateral tail vein. The mice were treated with luteolin (10 or 20 mg/kg, ip) daily for 23 d. On the 23rd day after tumor injection, the mice were sacrificed, and the lungs were collected, and metastatic foci in the lung surfaces were photographed. Tissue sections were analyzed with immunohistochemistry and HE staining. Results: Hypoxia changed the morphology of B16F10 cells in vitro from the cobblestone-like to mesenchymal-like strips, which was accompanied by increased cellular adhesion and invasion. Luteolin (5?50 ?mol/L) suppressed the hypoxia-induced changes in the cells in a dose-dependent manner. Hypoxia significantly decreased the expression of E-cadherin while increased the expression of N-cadherin in the cells (indicating the occurrence of EMT-like transformation), which was reversed by luteolin (5 ?mol/L). In B16F10 cells, luteolin up-regulated E-cadherin at least partly via inhibiting the ?3 integrin/FAK signal pathway. In experimental metastasis model mice, treatment with luteolin (10 or 20 mg/kg) reduced metastatic colonization in the lungs by 50%. Furthermore, the treatment increased the expression of E-cadherin while reduced the expression of vimentin and ?3 integrin in the tumor tissues. Conclusion: Luteolin inhibits the hypoxia-induced EMT in malignant melanoma cells both in vitro and in vivo via the regulation of ?3 integrin, suggesting that luteolin may be applied as a potential anticancer chemopreventative and chemotherapeutic agent. PMID:22983392

Ruan, Jun-shan; Liu, Yu-ping; Zhang, Lei; Yan, Ling-geng; Fan, Fang-tian; Shen, Cun-si; Wang, Ai-yun; Zheng, Shi-zhong; Wang, Shao-ming; Lu, Yin

2012-01-01

174

Oral Cavity as a Potential Source of Gastric Reinfection by Helicobacter pylori  

Microsoft Academic Search

Helicobacter pylori (Hp) is a common pathogen colonizing the a gastric mucosa, but some reports indicated that it may also be found in the oral cavity, which could serve as a reservoir of the bacteria and a source of gastric reinfection. Accordingly, we aimed to study whether the oral cavity, particularly gingival pockets, are colonized by Hp and whether it

El?bieta Karczewska; Joanna E. Konturek; Peter C. Konturek; Marta Cze?nikiewicz; Edward Sito; W?adys?aw Biela?ski; Nina Kwiecie?; Wojciech Obtu?owicz; Witold Ziemniak; Jolanta Majka; Eckhart G. Hahn; Stanislaw J. Konturek

2002-01-01

175

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

PubMed Central

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

Sharma, Akhilesh

2012-01-01

176

Polymeric microspheres for drug delivery to the oral cavity: an in vitro evaluation of mucoadhesive potential.  

PubMed

Polymeric microparticles were fabricated from Carbopol, polycarbophil, chitosan, or Gantrez using a "water-in-oil emulsification" solvent evaporation method. Mean particle sizes, as determined by laser diffraction, were in the range 23-38 microm. Electron microscopy revealed that all microparticles were spherical and of smooth surface morphology. In pH 7.0 phosphate buffered saline, the microspheres exhibited significantly increased swelling ratios and longer half-times of swelling than the corresponding powdered polymers. The relative merits of the potential usefulness of these microspheres as formulation tools for the enhanced retention of a therapeutic entity within the oral mucosa were evaluated by in vitro mucoadhesion tests. Tensile tests showed that all microspheres under consideration were capable of adhering to porcine esophageal mucosa, with particles prepared from the poly(acrylic acid)s exhibiting greater mucoadhesive strength than those constructed from chitosan or Gantrez. However, in elution experiments involving a challenge with artificial saliva, particles of chitosan or Gantrez were retained onto mucosal tissue for longer time periods than those assembled from the poly(acrylic acid)s. PMID:12884248

Kockisch, Sandra; Rees, Gareth D; Young, Simon A; Tsibouklis, John; Smart, John D

2003-08-01

177

Experimental oral inoculations in birds to evaluate potential definitive hosts of Neospora caninum.  

PubMed

Experimental oral inoculations to evaluate potential definitive hosts of Neospora caninum were conducted by feeding infected rodent tissues to 9 carnivorous birds of 4 species. Birds included 2 red-tailed hawks (Buteo jamaicensis), 2 turkey vultures (Cathartes aura), 2 barn owls (Tyto alba), and 3 American crows (Corvus brachyrhynchus). The rodents (mice or rats) had been inoculated with 100,000 culture-derived tachyzoites of N. caninum 1-6 mo before feeding to the birds. Fecal samples were collected from each bird daily for 1 mo after feeding rodents and examined for oocysts by fecal flotation. In addition, processed aliquots from all avian fecal samples were fed to BALB/c mice. Five weeks after feeding, mice were bled and sera were tested for antibodies against N. caninum. One to two months later, mice were killed and brain tissue was examined microscopically for protozoal cysts. While occasional oocysts were found in avian fecal samples, these were likely not N. caninum because they were not infective to BALB/c mice. It was concluded that the bird species tested are not likely to be definitive hosts of N. caninum. PMID:7472875

Baker, D G; Morishita, T Y; Brooks, D L; Shen, S K; Lindsay, D S; Dubey, J P

1995-10-01

178

1’-Acetoxychavicol acetate inhibits growth of human oral carcinoma xenograft in mice and potentiates cisplatin effect via proinflammatory microenvironment alterations  

PubMed Central

Background Oral cancers although preventable, possess a low five-year survival rate which has remained unchanged over the past three decades. In an attempt to find a more safe, affordable and effective treatment option, we describe here the use of 1’S-1’-acetoxychavicol acetate (ACA), a component of Malaysian ginger traditionally used for various medicinal purposes. Methods Whether ACA can inhibit the growth of oral squamous cell carcinoma (SCC) cells alone or in combination with cisplatin (CDDP), was explored both in vitro using MTT assays and in vivo using Nu/Nu mice. Occurrence of apoptosis was assessed using PARP and DNA fragmentation assays, while the mode of action were elucidated through global expression profiling followed by Western blotting and IHC assays. Results We found that ACA alone inhibited the growth of oral SCC cells, induced apoptosis and suppressed its migration rate, while minimally affecting HMEC normal cells. ACA further enhanced the cytotoxic effects of CDDP in a synergistic manner as suggested by combination index studies. We also found that ACA inhibited the constitutive activation of NF-?B through suppression of IKK?/? activation. Human oral tumor xenografts studies in mice revealed that ACA alone was as effective as CDDP in reducing tumor volume, and further potentiated CDDP effects when used in combination with minimal body weight loss. The effects of ACA also correlated with a down-regulation of NF-?B regulated gene (FasL and Bim), including proinflammatory (NF-?B and COX-2) and proliferative (cyclin D1) biomarkers in tumor tissue. Conclusion Overall, our results suggest that ACA inhibits the growth of oral SCC and further potentiates the effect of standard CDDP treatment by modulation of proinflammatory microenvironment. The current preclinical data could form the basis for further clinical trials to improve the current standards for oral cancer care using this active component from the Malaysian ginger. PMID:23043547

2012-01-01

179

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

PubMed Central

In 2007, International Agency for Cancer Research presented compelling evidence that linked smokeless tobacco use to the development of human oral cancer. While these findings imply vigorous local carcinogen metabolism, little is known regarding levels and distribution of Phase I, II and drug egress enzymes in human oral mucosa. In the study presented here, we integrated clinical data, 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 employed 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 ~2 fold inter-donor differences in protein levels. Previous studies have confirmed ~3.5 fold inter-donor variations in intraepithelial Phase II enzymes. Unlike the superficially located enzymes in non-replicating esophageal surface epithelium, IHC studies confirmed 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 links 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

180

High ubiquitous mitochondrial creatine kinase expression in hepatocellular carcinoma denotes a poor prognosis with highly malignant potential.  

PubMed

We previously reported the increased serum mitochondrial creatine kinase (MtCK) activity in patients with hepatocellular carcinoma (HCC), mostly due to the increase in ubiquitous MtCK (uMtCK), and high uMtCK mRNA expression in HCC cell lines. We explored the mechanism(s) and the relevance of high uMtCK expression in HCC. In hepatitis C virus core gene transgenic mice, known to lose mitochondrial integrity in liver and subsequently develop HCC, uMtCK mRNA and protein levels were increased in HCC tissues but not in non-tumorous liver tissues. Transient overexpression of ankyrin repeat and suppressor of cytokine signaling box protein 9 (ASB9) reduced uMtCK protein levels in HCC cells, suggesting that increased uMtCK levels in HCC cells may be caused by increased gene expression and decreased protein degradation due to reduced ASB9 expression. The reduction of uMtCK expression by siRNA led to increased cell death, and reduced proliferation, migration and invasion in HCC cell lines. Then, consecutive 105 HCC patients, who underwent radiofrequency ablation with curative intent, were enrolled to analyze their prognosis. The patients with serum MtCK activity >19.4 U/L prior to the treatment had significantly shorter survival time than those with serum MtCK activity ? 19.4 U/L, where higher serum MtCK activity was retained as an independent risk for HCC-related death on multivariate analysis. In conclusion, high uMtCK expression in HCC may be caused by hepatocarcinogenesis per se but not by loss of mitochondrial integrity, of which ASB9 could be a negative regulator, and associated with highly malignant potential to suggest a poor prognosis. PMID:24174293

Uranbileg, Baasanjav; Enooku, Kenichiro; Soroida, Yoko; Ohkawa, Ryunosuke; Kudo, Yotaro; Nakagawa, Hayato; Tateishi, Ryosuke; Yoshida, Haruhiko; Shinzawa, Seiko; Moriya, Kyoji; Ohtomo, Natsuko; Nishikawa, Takako; Inoue, Yukiko; Tomiya, Tomoaki; Kojima, Soichi; Matsuura, Tomokazu; Koike, Kazuhiko; Yatomi, Yutaka; Ikeda, Hitoshi

2014-05-01

181

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. PMID:23594406

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

2013-01-01

182

["Malignant" ARDS].  

PubMed

Acute respiratory failure and the "acute respiratory distress syndrome" (ARDS) are frequent medical conditions in critically ill patients. Various causes can potentially result in the development of ARDS. Two cases are presented, in which malignant diseases were identified as causes of the respiratory failure. The first patient was diagnosed with an acute myeloic leukemia M5 (FAB). In the second patient, lung histology revealed an adenocarcinoma of the lung. These case reports show that in addition to the classical causes of ARDS, specific disease entities can mimic this form of respiratory failure. Beside solid cancers and lymphomas, acute and progressive forms of inflammatory, parenchymal lung diseases (such as acute interstitial pneumonitis, acute eosinophilic pneumonia, diffuse alveolar hemorrhagia, and acute hypersensitivity pneumonitis) can manifest with this picture. As a consequence, the diagnostic workup of respiratory failure of unknown cause should include these entities. PMID:19562262

Metzelder, S K; Reinke, C; Walthers, E M; Barth, P; Vogelmeier, C; Neubauer, A; Bals, R

2009-10-01

183

Probiotics in oral health--a review.  

PubMed

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

Rao, Yadav; Lingamneni, Benhur; Reddy, Deepika

2012-01-01

184

Lymphoid Proliferations of Indeterminate Malignant Potential arising in Adults with Common Variable Immunodeficiency Disorders: Unusual Case Studies and Immunohistological Review in the Light of Possible Causative Events  

Microsoft Academic Search

Patients with common variable immunodeficiency disorders (CVIDs) who developed B cell lymphoproliferation of indeterminate\\u000a malignant potential are described in order to raise a discussion of the relationship between infection and lymphoproliferation\\u000a in infection prone patients. Those with CVID are at risk of developing either polyclonal or monoclonal lymphoproliferation\\u000a in part due to the dysregulation of their adaptive immune systems. The

Sara Pereira da Silva; Elena Resnick; Mary Lucas; Jennifer Lortan; Smita Patel; Charlotte Cunningham-Rundles; Kevin Gatter; Qingyan Liu; Elaine S. Jaffe; Helen Chapel

185

Depth sensitive oblique polarized reflectance spectroscopy of oral epithelial tissue  

NASA Astrophysics Data System (ADS)

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

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

2014-05-01

186

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

187

Eudraginated polymer blends: a potential oral controlled drug delivery system for theophylline.  

PubMed

Sustained release (SR) dosage forms enable prolonged and continuous deposition of the drug in the gastrointestinal (GI) tract and improve the bioavailability of medications characterized by a narrow absorption window. In this study, a new strategy is proposed for the development of SR dosage forms for theophylline (TPH). Design of the delivery system was based on a sustained release formulation, with a modified coating technique and swelling features aimed to extend the release time of the drug. Different polymers, such as Carbopol 71G (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m) dispersion of Eudragit (EUD) in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for micromeritic properties, drug concentration and in vitro drug release. It was found that the in vitro drug release rate decreased with increasing the amount of polymer. Coating with EUD resulted in a significant lag phase in the first two hours of dissolution in the acidic pH of simulated gastric fluid (SGF) due to decreased water uptake, and hence decreased driving force for drug release. Release became faster in the alkaline pH of simulated intestinal fluid (SIF) owing to increased solubility of both the coating and matrixing agents. The optimized formulation was subjected to in vivo studies in rabbits and the pharmacokinetic parameters of developed formulations were compared with the commercial (Asmanyl(®)) formulation. Asmanyl(®) tablets showed faster absorption (t(max) 4.0 h) compared to the TPH formulation showing a t(max) value of 8.0 h. The C(max) and AUC values of TPH formulation were significantly (p < 0.05) higher than those for Asmanyl(®), revealing relative bioavailability of about 136.93 %. Our study demonstrated the potential usefulness of eudraginated polymers for the oral delivery of the sparingly soluble drug theophylline. PMID:22472450

Emeje, Martins; John-Africa, Lucy; Isimi, Yetunde; Kunle, Olobayo; Ofoefule, Sabinus

2012-03-01

188

Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential  

Microsoft Academic Search

Well-differentiated encapsulated tumors of the thyroid gland with a follicular architecture may cause diagnostic difficulties. Questionable vascular or capsular penetration may raise the possibility of a follicular carcinoma, while focal nuclear clearing and grooves may suggest a diagnosis of papillary carcinoma. A proposal has recently been made to designate cases showing suggestive but not conclusive morphological evidence of malignancy along

Mauro Papotti; Jaime Rodriguez; Roberta De Pompa; Armando Bartolazzi; Juan Rosai

2005-01-01

189

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

190

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

PubMed Central

Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains unknown. Histological and genetic evidence has led to the proposal that low grade ovarian serous carcinomas (LGOSC) have a different etiology than high grade carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP). Common regions of chromosome (chr) 3 loss have been observed in all types of serous ovarian tumours, including benign, suggesting that these regions contain genes important in the development of all ovarian serous carcinomas. A high-density genome-wide genotyping bead array technology, which assayed >600,000 markers, was applied to a panel of serous benign and LMP tumours and a small set of LGOSC, to characterize somatic events associated with the most indolent forms of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and BRAF mutations. An increasing frequency of genomic anomalies was observed with pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and 10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all tumour types. Runs of homozygosity were most commonly observed on chr3, with the 3p12-p11 candidate tumour suppressor region the most frequently homozygous region in the genome. An LMP harboured a homozygous deletion on chr6 which created a GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types. Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS-mutation positive LMP cases displayed significantly more chromosomal aberrations than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of 12p, which harbours the KRAS gene, was particularly evident. A pathology review reclassified all TP53-mutation positive LGOSC cases, some of which acquired a HGOSC status. Taken together, our results support the view that LGOSC could arise from serous benign and LMP tumours, but does not exclude the possibility that HGOSC may derive from LMP tumours. PMID:22163003

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

2011-01-01

191

Prevalence of glutathione S-transferase M1 null polymorphism in tobacco users, oral leukoplakia and oral squamous cell carcinoma patients in South Indian population: A polymerase chain reaction study  

PubMed Central

Context: Tobacco abuse is a well-known risk factor for potentially malignant disorders as well as oral squamous cell carcinoma (SCC). Factors that influence tobacco-exposed individuals developing a malignancy may include a combination of total tobacco exposure and genetic susceptibility. Aim: This study was undertaken to determine the prevalence of the glutathione S-transferase M1 (GSTM1) null polymorphism in oral leukoplakia and oral SCC patients in South Indian population. Settings and Design: This case-control study was conducted in hospital setting on South Indian population. Materials and Methods: Totally, 280 subjects with a history of tobacco use, oral leukoplakia, oral SCC were included in this study. Three milliliter of blood was collected and transported under cold cycle and taken for evaluation of GSTM1 null polymorphism using Multiplex Polymerase Chain Reaction. Results and Discussion: On comparing the prevalence of GSTM1 null polymorphism among the group with subjects with habits and no oral lesions, oral leukoplakia and oral SCC, it was observed that there was a statistically significant association between GSTM1 null polymorphism and the different groups (P < 0.01). Conclusion: The lack of GSTM1 activity would make the oral tissues more susceptible to action of tobacco carcinogens and to the development of a high-grade level of dysplasia in oral leukoplakia and thereby increases the susceptibility of lesion to undergo malignant changes.

Tanwar, Renu; Iyengar, Asha R.; Nagesh, K. S.; Patil, Seema; Subhash, B. V.

2015-01-01

192

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

PubMed Central

Background and Objectives: Oral mucositis is a common and debilitating complication of radiotherapy, which is associated with significant morbidity. It is therefore extremely important that mucositis be prevented, or at least treated to reduce its severity and sequelae. The objective of the study was to manage oral mucositis induced by radiotherapy and to reduce pain by using Benzydamine hydrochloride (0.15%), Chlorhexidine (0.2%), and Povidone iodine (5%). Results: Benzydamine hydrochloride was observed to be effective and delayed the development of severe form of mucositis and appears more efficient in the management of radiation-induced mucositis. Conclusion: Benzydamine hydrochloride (0.15%) is safe, well tolerated, helps not just in delaying the progression of mucositis but also reduces the intensity of pain. PMID:22114446

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

2011-01-01

193

Telomerase reverse transcriptase potentially promotes the progression of oral squamous cell carcinoma through induction of epithelial-mesenchymal transition.  

PubMed

In recent years, researchers have found the critical role of telomerase in cellular transformation, proliferation, stemness and cell survival. High levels of telomerase reverse transcriptase (TERT) expression and telomerase activation have been reported in most cancer cells. Moreover, overexpression of human TERT (hTERT) is reported to be correlated with advanced invasive stage of the tumor progression and poor prognosis. Epithelial-mesenchymal transition (EMT), characterized by the loss of the cell-cell contact of epithelial cells and the acquisition of migratory and motile properties, is known to be a central mechanism responsible for invasiveness and metastasis of various cancers. Thus, we investigated whether hTERT plays a potential role in the development of EMT. As we expected, our clinical results showed that hTERT is overexpressed in oral epithelial dysplasia (OED) and OSCC tissues and correlates with clinical aggressiveness of oral squamous cell carcinoma (OSCC) patients. We then overexpressed hTERT in primary human oral epithelial cells (HOECS) and found that hTERT has the potential to prolong the lifespan, a process confering the characteristics of EMT by activating the Wnt/?-catenin pathway. Our findings provided an explanation for the aggressive nature of human tumors overexpressing hTERT and the possibly mechanism that links hTERT to EMT property, which represents a possible therapeutic target in highly metastatic cancers. PMID:25775973

Zhao, Tengda; Hu, Fengchun; Qiao, Bin; Chen, Zhifeng; Tao, Qian

2015-05-01

194

Epigenetics in the hematologic malignancies  

PubMed Central

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

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

2014-01-01

195

IL6 and IL8: Potential biomarkers for oral cavity and oropharyngeal SCCA  

Microsoft Academic Search

Problem: Since morbidity and mortality rates due to oral cavity and oropharyngeal squamous cell carcinoma (OSCC) have improved little in the past 30 years, early detection or prevention of this disease is likely to be most effective. Using laser-capture microdissection, we identified the expression of 2 cellular genes that are uniquely associated with OSCC: IL-6 and IL-8. We then set

Maie St John; Yang Li; Xiaofeng Zhou; Honghu Liu; Elliot Abemayor; David T. W. Wong

2004-01-01

196

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. PMID:24976694

Carrozzo, Marco; Scally, Kara

2014-01-01

197

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

PubMed

Helicobacter pylori (Hp) is a common pathogen colonizing the a gastric mucosa, but some reports indicated that it may also be found in the oral cavity, which could serve as a reservoir of the bacteria and a source of gastric reinfection. Accordingly, we aimed to study whether the oral cavity, particularly gingival pockets, are colonized by Hp and whether it could be the source of gastric reinfection. We studied 329 patients with dyspeptic symptoms (257 with chronic gastritis, 15 with gastric ulcer, and 57 with duodenal ulcer). The [13C]urea breath test (UBT), gastroscopy, and Hp culture from gastric biopsies were carried out, and material was collected from the oral cavity (gingival pocket) for bacteriological culture and genomic DNA studies. The serum was obtained for anti-Hp IgG and anti-CagA assays and saliva for anti-Hp IgA determination using the ELISA technique. Bacteria in material from gingival pockets and biopsies from the corpus and antrum of stomach of 30 DU patients before and after Hp eradication were also examined by PCR technique, using primers specific for 16S rRNA. All Hp-positive patients (276) were subjected to one week of triple therapy (omeprazole 2 x 20 mg twice a day, clarithromycin 2 x 500 mg twice a day, and metronidazole 2 x 500 mg twice a day). The measurements described above were then repeated at four weeks and six months. Bacteriological culture showed the presence of Hp in the material from oral cavity in about 50% of patients, whereas UBT, used as a gold standard, revealed gastric Hp infection in about 84% of these patients. The eradication was successful in the majority of patients (87%), but about 13% of them were still Hp positive after four weeks and about 21% after six months. Four weeks after Hp therapy, Hp was found in culture from oral samples in 23% (P < 0.05 vs initial) and after six months in 35.1%. The IgA levels recorded in saliva were in a close agreement with UBT results. Hp DNA assessed by PCR in 30 DUs before eradication of Hp was detected in 95% of antral mucosa, 90% in corpus mucosa, and in 35% of gingival pocket material, and after eradication therapy Hp DNA values fell to 25%, 20%, and 10%, respectively. In conclusion, Hp is commonly detected in the oral cavity of patients with dyspeptic symptoms, but the gastric reinfection does not appear to occur in the patients despite oral Hp colonization. PMID:12018924

Karczewska, Elzbieta; Konturek, Joanna E; Konturek, Peter C; Cze?nikiewicz, Marta; Sito, Edward; Biela?ski, W?adys?aw; Kwiecie?, Nina; Obtu?owicz, Wojciech; Ziemniak, Witold; Majka, Jolanta; Hahn, Eckhart G; Konturek, Stanislaw J

2002-05-01

198

Downregulating FPR restrains xenograft tumors by impairing the angiogenic potential and invasive capability of malignant glioma cells  

Microsoft Academic Search

G-protein-coupled formylpeptide receptor (FPR) has recently been found to be functionally expressed in gliomas and are probably involved in their malignant biological behavior. In an attempt to explore the therapeutic significance of FPRs, we used wild-type human glioblastoma cells (U87), the corresponding FPR short-interfering RNA transfected (siRNA U87) cells, and mock-transfected U87 cells (mock U87) to establish xenografts in mice

Dai-lun Chen; Yi-fang Ping; Shi-cang Yu; Jian-hong Chen; Xiao-hong Yao; Xue-feng Jiang; Hua-rong Zhang; Qing-liang Wang; Xiu-wu Bian

2009-01-01

199

AVX-470: A Novel Oral Anti-TNF Antibody with Therapeutic Potential in Inflammatory Bowel Disease  

PubMed Central

Background Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the GI tract that is currently treated with injected monoclonal antibodies specific for tumor necrosis factor (TNF). We developed and characterized AVX-470, a novel polyclonal antibody specific for human TNF. We evaluated the oral activity of AVX-470m, a surrogate antibody specific murine TNF, in several well-accepted mouse models of IBD. Methods AVX-470 and AVX-470m were isolated from the colostrum of dairy cows that had been immunized with TNF. The potency, specificity and affinity of both AVX-470 and AVX-470m were evaluated in vitro and compared with infliximab. AVX-470m was orally administered to mice either before or after induction of colitis and activity was measured by endoscopy, histopathology, immunohistochemistry and quantitative measurement of mRNA levels. Colitis was induced using either 2,4,6-trinitrobenzene sulfonate (TNBS) or dextran sodium sulfate (DSS). Results AVX-470 and AVX-470m were shown to be functionally comparable in vitro. Moreover, the specificity, neutralizing potency and affinity of AVX-470 were comparable to infliximab. Orally administered AVX-470m effectively reduced disease severity in several mouse models of IBD. Activity was comparable to that of oral prednisolone or parenteral etanercept. The antibody penetrated the colonic mucosa and inhibited TNF-driven mucosal inflammation with minimal systemic exposure. Conclusions AVX-470 is a novel polyclonal anti-TNF antibody with an in vitro activity profile comparable to that of infliximab. Oral administration of a surrogate antibody specific for mouse TNF is effective in treating mouse models of IBD, delivering the anti-TNF to the site of inflammation with minimal systemic exposure. PMID:23949620

Bhol, Kailash C.; Tracey, Daniel E.; Lemos, Brenda R.; Lyng, Gregory D.; Erlich, Emma C.; Keane, David M.; Quesenberry, Michael S.; Holdorf, Amy D.; Schlehuber, Lisa D.; Clark, Shawn A.; Fox, Barbara S.

2013-01-01

200

Aerobic bacterial oral flora of garter snakes: development of normal flora and pathogenic potential for snakes and humans.  

PubMed Central

Garter snakes that are used for scientific laboratory studies or kept as exotic pets often become ill and die early in captivity. They may also act as reservoirs of potential human pathogens or transmit infection to man. A total of 126 strains of aerobic and facultative bacteria, most potential human and snake pathogens, were isolated from 82 garter snake oropharyngeal cultures. Coagulase-negative Staphylococcus species were the most common species isolated. Acinetobacter calcoaceticus var. anitratus, Hafnia alvei, Arizona hinshawii, Salmonella species, Shigella species, Klebsiella oxytoca, and Pseudomonas aeruginosa were among the potential pathogens isolated. The spectrum of bacteria with potential for causing oral and pulmonary infections in garter snakes is greater than has been previously appreciated. Garter snakes should also be considered reservoirs of human pathogens, and appropriate precautions should be taken by laboratory personnel and pet owners. PMID:7240404

Goldstein, E J; Agyare, E O; Vagvolgyi, A E; Halpern, M

1981-01-01

201

Non-hematopoietic PAR-2 is essential for matriptase-driven pre-malignant progression and potentiation of ras-mediated squamous cell carcinogenesis.  

PubMed

The membrane-anchored serine protease, matriptase, is consistently dysregulated in a range of human carcinomas, and high matriptase activity correlates with poor prognosis. Furthermore, matriptase is unique among tumor-associated proteases in that epithelial stem cell expression of the protease suffices to induce malignant transformation. Here, we use genetic epistasis analysis to identify proteinase-activated receptor (PAR)-2-dependent inflammatory signaling as an essential component of matriptase-mediated oncogenesis. In cell-based assays, matriptase was a potent activator of PAR-2, and PAR-2 activation by matriptase caused robust induction of nuclear factor (NF)?B through G?i. Importantly, genetic elimination of PAR-2 from mice completely prevented matriptase-induced pre-malignant progression, including inflammatory cytokine production, inflammatory cell recruitment, epidermal hyperplasia and dermal fibrosis. Selective ablation of PAR-2 from bone marrow-derived cells did not prevent matriptase-driven pre-malignant progression, indicating that matriptase activates keratinocyte stem cell PAR-2 to elicit its pro-inflammatory and pro-tumorigenic effects. When combined with previous studies, our data suggest that dual induction of PAR-2-NF?B inflammatory signaling and PI3K-Akt-mTor survival/proliferative signaling underlies the transforming potential of matriptase and may contribute to pro-tumorigenic signaling in human epithelial carcinogenesis. PMID:24469043

Sales, K U; Friis, S; Konkel, J E; Godiksen, S; Hatakeyama, M; Hansen, K K; Rogatto, S R; Szabo, R; Vogel, L K; Chen, W; Gutkind, J S; Bugge, T H

2015-01-15

202

Prevalence and potential influencing factors of non-nutritive oral behaviors of veal calves on commercial farms.  

PubMed

Veal calves raised under intensive conditions may express non-nutritive oral behaviors. When expressed in an abnormal way, these behaviors can be a sign of mental suffering and reduced welfare due to a mismatch between environmental or management features and the animal's needs. The aims of this study were to estimate the prevalence of non-nutritive oral behaviors in a large sample of veal farms in Europe and to determine the potential influencing factors present at farm level. Data were collected on 157 commercial veal farms in the 3 main veal-producing countries in Europe (the Netherlands, France, and Italy). Observations of 3 non-nutritive oral behaviors (manipulating substrates, tongue rolling, and manipulating a penmate) were performed when calves were aged 14 wk, and the prevalence of these behaviors was calculated. Information on management practices and characteristics of the building and equipment were collected on all farms to assess potential influencing factors for each of the 3 behaviors. Odds ratios and 95% confidence intervals were calculated to evaluate the effect of each individual factor within a generalized linear model. The mean percentage of calves per farm performing manipulating substrates was 11.0 ± 0.46%, performing tongue rolling 2.8 ± 0 .18%, and manipulating a penmate 2.7 ± 0.09%, with a high range between farms. Allowing more space for calves than the legal minimum requirement of 1.8 m(2)/ calf and housing them in groups of >10 calves/pen reduced the incidences of manipulating substrates and tongue rolling. Incidence of manipulating substrates was lower for calves fed maize silage compared with calves fed cereal grain, pellets, or muesli. A higher risk of tongue rolling was found when baby-boxes (i.e., single housing during the first 5 to 8 wk) were not used. Risk of calves manipulating a penmate was higher for calves of milk- or meat-type breeds compared with dual-purpose breeds and for calves fed with 280 to 380 kg compared with those fed >380 kg of milk powder in total for the fattening period. The study allowed assessment of multiple factors across farms that showed variety in terms of conditions and level of non-nutritive oral behaviors. Identification of the factors influencing non-nutritive oral behavior is helpful to define potential actions that could be taken on farms to improve the welfare of calves and reduce the prevalence of these behaviors. PMID:25218744

Leruste, H; Brscic, M; Cozzi, G; Kemp, B; Wolthuis-Fillerup, M; Lensink, B J; Bokkers, E A M; van Reenen, C G

2014-11-01

203

Oral Viscous Budesonide: A Potential New Therapy for Eosinophilic Esophagitis in Children  

Microsoft Academic Search

BACKGROUND:Eosinophilic esophagitis (EE) is a disorder characterized typically by pan-esophageal eosinophilia. We evaluate a palatable, long-acting topical corticosteroid preparation for the treatment of EE.STUDY DESIGN:This is a retrospective analysis of symptoms, endoscopic and histologic findings, efficacy, and safety of treatment in children with EE receiving oral viscous budesonide. Response to therapy was determined histologically by the number of eos\\/hpf. Patients

Seema S. Aceves; John F. Bastian; Robert O. Newbury; Ranjan Dohil

2007-01-01

204

Benefit Cost Scenarios of Potential Oral Rabies Vaccination for Skunks in California  

Microsoft Academic Search

Scenario-based analyses were computed for benefits and costs linked with hypothetical oral rabies vaccination (ORV) campaigns to contain or eliminate skunk-variant rabies in skunks (Mephitis mephitis) in California, USA. Scenario 1 assumed baiting eight zones (43,388 km2 total) that comprised 73% of known skunk rabies locations in the state. Scenario 2 also assumed baiting these eight zones, but further assumed

Stephanie A. Shwiff; Ray T. Sterner; Michele T. Jay; Ben Sun; Dennis Slate

2009-01-01

205

[Malignant hyperthermia].  

PubMed

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

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

2014-12-01

206

Diagnostic aids in the screening of oral cancer  

PubMed Central

The World Health Organization has clearly indentified prevention and early detection as major objectives in the control of the oral cancer burden worldwide. At the present time, screening of oral cancer and its pre-invasive intra-epithelial stages, as well as its early detection, is still largely based on visual examination of the mouth. There is strong available evidence to suggest that visual inspection of the oral mucosa is effective in reducing mortality from oral cancer in individuals exposed to risk factors. Simple visual examination, however, is well known to be limited by subjective interpretation and by the potential, albeit rare, occurrence of dysplasia and early OSCC within areas of normal-looking oral mucosa. As a consequence, adjunctive techniques have been suggested to increase our ability to differentiate between benign abnormalities and dysplastic/malignant changes as well as to identify areas of dysplasia/early OSCC that are not visible to naked eye. These include the use of toluidine blue, brush biopsy, chemiluminescence and tissue autofluorescence. The present paper reviews the evidence supporting the efficacy of the aforementioned techniques in improving the identification of dysplastic/malignant changes of the oral mucosa. We conclude that available studies have shown promising results, but strong evidence to support the use of oral cancer diagnostic aids is still lacking. Further research with clear objectives, well-defined population cohorts, and sound methodology is strongly required. PMID:19284694

Fedele, Stefano

2009-01-01

207

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. PMID:19596745

Palombo, Enzo A.

2011-01-01

208

Oral candidiasis  

PubMed Central

Oral candidiasis is a common opportunistic infection of the oral cavity caused by an overgrowth of Candida species, the commonest being Candida albicans. The incidence varies depending on age and certain predisposing factors. There are three broad groupings consisting of acute candidiasis, chronic candidiasis, and angular cheilitis. Risk factors include impaired salivary gland function, drugs, dentures, high carbohydrate diet, and extremes of life, smoking, diabetes mellitus, Cushing's syndrome, malignancies, and immunosuppressive conditions. Management involves taking a history, an examination, and appropriate antifungal treatment with a few requiring samples to be taken for laboratory analysis. In certain high risk groups antifungal prophylaxis reduces the incidence and severity of infections. The prognosis is good in the great majority of cases. PMID:12185216

Akpan, A; Morgan, R

2002-01-01

209

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

210

Malignant hypertension  

MedlinePLUS

... for malignant hypertension if you have had: Kidney failure Renal hypertension caused by renal artery stenosis ... An eye examination will reveal changes that indicate high blood ... failure, as well as other complications, may develop. Tests ...

211

Aggressive malignant phyllodes tumor  

PubMed Central

Introduction Originally described in 1838 by Muller, phyllodes tumor is a rare fibroepithelial neoplasm which represents roughly 0.3–0.9% of all breast cancers. Phyllodes tumor are divided into benign, borderline and malignant histologic categories. Malignant phyllodes tumor represent anywhere from 10–30% of all phyllodes tumors. This group has both the potential to recur locally and metastasize, however not all malignant phyllodes behave this way. The challenge lays in predicting which tumor will recur locally or metastasize. Distinguishing this subset of malignant phyllodes tumor is paramount. Presentation of case We present a case of malignant phyllodes which presented with metastatic disease. What is fascinating about this case is not only the initial presentation but also the aggressiveness of this variation of phyllodes tumor. The patient initially presented with a large mass which encompassed her whole right breast. On surgical pathology the mass measured roughly 31 cm in diameter and weighed over 10 kg. Within 5 weeks from surgery the patient had suffered brain metastases and also 6 local recurrent tumors. The patient passed roughly 11 weeks after her first visit to our office. Conclusion Despite biopsy proven malignant phyllodes tumor, it was near impossible to predict such a rapid course of disease progression in our patient. Our case illustrates the unpredictable nature of this disease in general and it possibly sheds light on a variant of the disease which had undergone an aggressive transformation. PMID:25697402

Roberts, Nathan; Runk, Dianne M.

2015-01-01

212

Oral Leukoplakia – Is Biopsy at the Initial Appointment a Must?  

PubMed Central

Background: Oral leukoplakia is a potentially malignant disorder of the oral cavity. Leukoplakias with chances of undergoing malignant transformation owing to the presence of dysplastic changes may not be clinically distinguishable from leukoplakias without dysplasia. The study was carried out to evaluate the usefulness of biopsy in assessing the clinico-pathologic correlations of oral leukoplakia at the patient’s initial visit. Materials and Methods: Hospital records with clinical diagnosis of oral leukoplakia were retrospectively analysed. All these patients had undergone biopsy in their initial visit. Histopathological slides were reviewed and reported by a single pathologist. Diagnosis agreement was considered to be present if the clinical diagnosis matched the histopathological diagnosis. Misdiagnosis was considered if the clinical diagnosis did not match the histopathological diagnosis and underdiagnosis when malignancy was detected on histopathological examination. Results: A total of 115 patients were clinically diagnosed with oral leukoplakia. According to clinical appearance of the leukoplakia patch was categorized in to three types viz homogeneous leukoplakia (n= 24 i.e. 20.87%), speckled leukoplakia (n=76 i.e. 66.08%) and verrucous leukoplakia (n=15 i.e. 13.04%). Histopathological examination confirmed clinical diagnosis in 88 cases (a diagnosis agreement of 76.52%). Histopathological examination of 19 cases revealed a different diagnosis, thus categorized as misdiagnosis (16.52%) and 8 cases had unexpected malignancy which accounted for underdiagnosis in 6.96% cases. There was dysplasia in 45 (51.13%) of the histopathologically confirmed cases of leukoplakia. Conclusion: The clinical appearance of suspicious white lesions does not provide a true nature of its disease status and malignant changes may be missed. PMID:25302256

Mutalik, Vimi S.; Pai, Keerthilatha M; Naikmasur, Venkatesh G.; Phaik, Khoo Suan

2014-01-01

213

Malignant Hyperthermia Association of the United States  

MedlinePLUS

... Shop Official MHAUS Home Page What Is MH? Malignant hyperthermia (MH) is a potentially fatal, inherited disorder ... Donations Save Lives! January 7, 2015 Anesthesia Provider Malignant Hyperthermia Experiences Survey December 31, 2014 Fiscal Year ...

214

Kinesin Family member 4A: A Potential Predictor for Progression of Human Oral Cancer  

PubMed Central

Background Kinesin family member 4A (KIF4A), a microtubule-based motor protein, was implicated in regulation of chromosomal structure and kinetochore microtubule dynamics. Considering the functions of KIF4A, we assumed that KIF4A is involved in progression of oral squamous cell carcinomas (OSCCs) via activation of the spindle assembly checkpoint (SAC). However, little is known about the relevance of KIF4A in the behavior of OSCC. We investigated the KIF4A expression status and its functional mechanisms in OSCC. Methods The KIF4A expression levels in seven OSCC-derived cells were analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunoblotting analyses. Using a KIF4A knockdown model, we assessed the expression of (SAC)-related molecules (BUB1, MAD2, CDC20, and cyclin B1), cell-cycle, and cellular proliferation. In addition to in vitro data, the clinical correlation between the KIF4A expression levels in primary OSCCs (n = 106 patients) and the clinicopathologic status by immunohistochemistry (IHC) also were evaluated. Results KIF4A mRNA and protein were up-regulated significantly (P < 0.05) in seven OSCC-derived cells compared with human normal oral keratinocytes. In the KIF4A knockdown cells, SAC activation was observed via increased BUB1 expression on the kinetochores, appropriate kinetochore localization of MAD2, down-regulation of CDC20, up-regulation of cyclin B1, and cell-cycle arrested at G2/M phase. The results showed that cellular proliferation of KIF4A knockdown cells decreased significantly (P < 0.05) compared with control cells. IHC showed that KIF4A expression in primary OSCCs was significantly (P < 0.05) greater than in the normal oral counterparts and that KIF4A-positive OSCCs were correlated closely (P < 0.05) with tumoral size. Conclusions Our results proposed for the first time that KIF4A controls cellular proliferation via SAC activation. Therefore, KIF4A might be a key regulator for tumoral progression in OSCCs. PMID:24386490

Minakawa, Yasuyuki; Kasamatsu, Atsushi; Koike, Hirofumi; Higo, Morihiro; Nakashima, Dai; Kouzu, Yukinao; Sakamoto, Yosuke; Ogawara, Katsunori; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

2013-01-01

215

Exciting new advances in oral cancer diagnosis: avenues to early detection  

PubMed Central

The prognosis for patients with oral squamous cell carcinoma remains poor in spite of advances in therapy of many other malignancies. Early diagnosis and treatment remains the key to improved patient survival. Because the scalpel biopsy for diagnosis is invasive and has potential morbidity, it is reserved for evaluating highly suspicious lesions and not for the majority of oral lesions which are clinically not suspicious. Furthermore, scalpel biopsy has significant interobserver and intraobserver variability in the histologic diagnosis of dysplasia. There is an urgent need to devise critical diagnostic tools for early detection of oral dysplasia and malignancy that are practical, noninvasive and can be easily performed in an out-patient set-up. Diagnostic tests for early detection include brush biopsy, toluidine blue staining, autofluorescence, salivary proteomics, DNA analysis, biomarkers and spectroscopy. This state of the art review critically examines these tests and assesses their value in identifying oral squamous cell carcinoma and its precursor lesions. PMID:21798030

2011-01-01

216

Ascending parabrachio-thalamo-striatal pathways: Potential circuits for integration of gustatory and oral motor functions.  

PubMed

The medial parabrachial nucleus (MPB) and external part of the medial parabrachial nucleus (MPBE) relay gustatory, oral mechanosensory and other visceral information in the rat brain and reportedly project not only to the parvicellular part of the posteromedial ventral thalamic nucleus (VPMpc) but also to the ventrocaudal part of the intralaminar thalamic nuclei. Generally, the intralaminar thalamic nuclei project topographically to the caudate putamen (CPu); however, it is unclear where the ventrocaudal part of the intralaminar thalamic nuclei projects within the CPu. Thus, we visualized neural pathways from the MPB and MPBE to the CPu via the ventrocaudal part of the intralaminar thalamic nuclei using an anterograde tracer, biotinylated dextran amine, and a retrograde tracer, cholera toxin B subunit. We found that the MPB and MPBE sent a relatively stronger input to the ventrocaudal part of the intralaminar thalamic nuclei such as the oval paracentral thalamic nucleus (OPC), central medial thalamic nucleus (CM) and parafascicular thalamic nucleus (PF) and retroreuniens area (RRe) as compared to the VPMpc. In turn, these thalamic nuclei projected to the ventral part of the CPu with the topographical arrangement as follows: the OPC to the ventrocentral part of the CPu; ventrolateral part of the PF to the ventrolateral part of the CPu; and the caudal part of the CM, ventromedial part of the PF and RRe to the ventromedial part of the CPu. Further, we found that the VPMpc rather projected to the interstitial nucleus of the posterior limb of the anterior commissure than the CPu. The ventral part of the CPu is reported to be involved in jaw movement as well as food and water intake functions. Therefore, these parabrachio-thalamo-striatal pathways that we demonstrated here suggest that gustatory and oral mechanosensory information affects feeding behavior within the ventral part of the CPu. PMID:25743252

Iwai, H; Kuramoto, E; Yamanaka, A; Sonomura, T; Uemura, M; Goto, T

2015-05-21

217

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. PMID:24817792

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

218

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

PubMed

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

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

2007-03-01

219

Optimizing therapeutic efficacy of chemopreventive agents: A critical review of delivery strategies in oral cancer chemoprevention clinical trials  

PubMed Central

Due to its characterized progression from recognized premalignant oral epithelial changes (i.e., oral epithelial dysplasia) to invasive cancer, oral squamous cell carcinoma represents an optimal disease for chemopreventive intervention prior to malignant transformation. The primary goal of oral cancer chemoprevention is to reverse, suppress, or inhibit the progression of premalignant lesions to cancer. Over the last several decades, numerous oral cancer chemoprevention clinical trials have assessed the therapeutic efficacy of diverse chemopreventive agents. The standard of care for more advanced oral dysplastic lesions entails surgical excision and close clinical follow-up due to the potential (~33%) for local recurrence at a similar or more advanced histological stage. The purpose of this review was to identify prominent oral cancer chemoprevention clinical trials, assess their overall therapeutic efficacy, and delineate effects of local versus systemic drug administration. In addition, these compiled clinical trial data present concepts for consideration in the design and conduction of future clinical trials. PMID:22013393

Holpuch, Andrew S.; Desai, Kashappa-Goud H.; Schwendeman, Steven P.; Mallery, Susan R.

2011-01-01

220

E-Cadherin truncation and sialyl Lewis-X overexpression in oral squamous cell carcinoma and oral precancerous conditions.  

PubMed

The present study aimed to determine significance of E-cadherin, a cell adhesion molecule, and sialyl Lewis-X (sLeX), a cell surface antigen, in oral carcinogenesis. Expressions of E-cadherin and sLeX were detected using western blot analysis from oral malignant (n=25), and oral precancerous tissues (OPC, n=20) and their adjacent normal tissues. An altered expression of E-cadherin (E-cad) and sLeX was observed in malignant and precancerous tissues. E-cad western blot revealed presence of two bands, a 120 kDa (native, E-cad120) and a 97 kDa (known as truncated E-cad97). The accumulation of truncated E-cad97 and sLeX in malignant and OPC tissues compared to their adjacent normal tissues was observed. Receiver's Operating Characteristics (ROC) curve analysis showed good discriminatory efficacy of E-cad97, E-cad97:120 ratio and sLeX between the malignant and adjacent. normal tissues. Further, a positive correlation of E-cad97 and sLeX overexpression with advanced stage of the disease and lymphnode metastasis was observed. The data suggest that E-cadherin truncation and sLeX overexpression are early events which may facilitate the tumor cells to metastasize. Also, overexpression E-cad97 and sLeX in OPC tissues may be useful to predict metastatic potentials of tumors at an early stage of oral carcinogenesis. Key words: Oral cancer, oral precancerous conditions, E-cadherin, sialyl Lewis-X, metastasis. PMID:19152244

Shah, M H; Sainger, R N; Telang, S D; Pancholi, G H; Shukla, S N; Patel, P S

2009-01-01

221

Malignant mesothelioma  

PubMed Central

Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10–20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis. PMID:19099560

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

2008-01-01

222

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. PMID:23526965

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

2013-01-01

223

Familial malignant retroperitoneal paraganglioma.  

PubMed Central

Paragangliomas are neuroendocrine tumours and those occurring in the head and neck have well recognized familial association. Retroperitoneal paragangliomas are uncommon and we present two cases of familial malignant retroperitoneal paraganglioma. Review of the literature revealed marked differences in the incidence and malignant potential of familial and non-familial paraganglioma. In contrast to the cases reported here, familial tumours are generally benign, though they may occur at multiple sites. Familial and non-familial paragangliomas may indeed be different disease entities. Images Figure 1 Figure 2 Figure 3 PMID:2559401

Sebastian, J. P.; Williams, S. E.; Wells, M.; Peake, M. D.

1989-01-01

224

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. PMID:24885002

2014-01-01

225

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

226

MET and PI3K/mTOR as a Potential Combinatorial Therapeutic Target in Malignant Pleural Mesothelioma  

PubMed Central

Malignant pleural mesothelioma (MPM) is an aggressive disease with a poor prognosis. Studies have shown that both MET and its key downstream intracellular signaling partners, PI3K and mTOR, are overexpressed in MPM. Here we determined the combinatorial therapeutic efficacy of a new generation small molecule inhibitor of MET, ARQ 197, and dual PI3K/mTOR inhibitors NVP-BEZ235 and GDC-0980 in mesothelioma cell and mouse xenograft models. Cell viability results show that mesothelioma cell lines were sensitive to ARQ 197, NVP-BEZ235 and GDC-0980 inhibitors. The combined use of ARQ 197 with either NVP-BEZ235 or GDC-0980, was synergistic (CI<1). Significant delay in wound healing was observed with ARQ 197 (p<0.001) with no added advantage of combining it with either NVP-BEZ235 or GDC-0980. ARQ 197 alone mainly induced apoptosis (20±2.36%) that was preceded by suppression of MAPK activity, while all the three suppressed cell cycle progression. Both GDC-0980 and NVP-BEZ235 strongly inhibited activities of PI3K and mTOR as evidenced from the phosphorylation status of AKT and S6 kinase. The above observation was further substantiated by the finding that a majority of the MPM archival samples tested revealed highly active AKT. While the single use of ARQ 197 and GDC-0980 inhibited significantly the growth of MPM xenografts (p<0.05, p<0.001 respectively) in mice, the combination of the above two drugs was highly synergistic (p<0.001). Our results suggest that the combined use of ARQ 197/NVP-BEZ235 and ARQ 197/GDC-0980 is far more effective than the use of the drugs singly in suppressing MPM tumor growth and motility and therefore merit further translational studies. PMID:25221930

Kanteti, Rajani; Dhanasingh, Immanuel; Kawada, Ichiro; Lennon, Frances E.; Arif, Qudsia; Bueno, Raphael; Hasina, Rifat; Husain, Aliya N.; Vigneswaran, Wickii; Seiwert, Tanguy; Kindler, Hedy L.; Salgia, Ravi

2014-01-01

227

Definitions of Single and Subsequent Primaries for Hematologic Malignancies  

Cancer.gov

While it is recognized that some malignancies occur predominantly (or even exclusively) in liquid or solid form, because so many malignancies can potentially arise as either leukemias or lymphomas (or both), all hematopoietic malignancies are assumed to have this potential. 2. Malignancies of the lymphoid series are considered to be different from those of the myeloid series.

228

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

PubMed Central

OBJECTIVE: To assess the suitability of using oral-fluid samples for determining the prevalence of immunity to vaccine-preventable infections. METHODS: Paired blood and oral-fluid samples were obtained from 853 individuals of all ages from a rural Ethiopian community. Oral fluid around the gums was screened for measles- and rubella-specific antibodies using enhanced IgG antibody capture (GAC) enzyme-linked immunosorbent assays (ELISAs), and for anti-HBc antibodies using a prototype GACELISA. IgG antibodies in serum to measles, rubella and HBc were determined using commercial ELISAs. FINDINGS: Relative to serum, oral fluid assay sensitivity and specificity were as follows: 98% and 87% for measles, 79% and 90% for rubella, and 43% and 87% for anti-HBc. These assay characteristics yielded population prevalence estimates from oral fluid with a precision equal to that of serum for measles (all ages) and rubella (ages < 20 years). CONCLUSION: Our results suggest that oral fluid could have the potential to replace serum in IgG antibody prevalence surveys. Further progress requires assessment of variation in assay performance between populations as well as the availability of standardized, easy to use assays. PMID:11477961

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

2001-01-01

229

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

230

Can the microRNA signature distinguish between thyroid tumors of uncertain malignant potential and other well-differentiated tumors of the thyroid gland?  

PubMed

The term 'thyroid tumors of uncertain malignant potential' (TT-UMP) was coined by surgical pathologists to define well-differentiated tumors (WDT) showing inconclusive morphological evidence of malignancy or benignity. We have analyzed the expression of microRNA (miRNA) in a training set of 42 WDT of different histological subtypes: seven follicular tumors of UMP (FT-UMP), six WDT-UMP, seven follicular thyroid adenomas (FTA), 11 conventional papillary thyroid carcinomas (C-PTC), five follicular variants of PTC (FV-PTC), and six follicular thyroid carcinomas (FTC), which led to the identification of about 40 deregulated miRNAs. A subset of these altered miRNAs was independently validated by qRT-PCR, which included 18 supplementary TT-UMP (eight WDT-UMP and ten FT-UMP). Supervised clustering techniques were used to predict the first 42 samples. Based on the four possible outcomes (FTA, C-PTC, FV-PTC, and FTC), about 80% of FTA and C-PTC and 50% of FV-PTC and FTC samples were correctly assigned. Analysis of the independent set of 18 WDT-UMP by quantitative RT-PCR for the selection of the six most discriminating miRNAs was unable to separate FT-UMP from WDT-UMP, suggesting that the miRNA signature is insufficient in characterizing these two clinical entities. We conclude that considering FT-UMP and WDT-UMP as distinct and specific clinical entities may improve the diagnosis of WDT of the thyroid gland. In this context, a small set of miRNAs (i.e. miR-7, miR-146a, miR-146b, miR-200b, miR-221, and miR-222) appears to be useful, though not sufficient per se, in distinguishing TT-UMP from other WDT of the thyroid gland. PMID:21778212

Lassalle, Sandra; Hofman, Véronique; Ilie, Marius; Bonnetaud, Christelle; Puisségur, Marie-Pierre; Brest, Patrick; Loubatier, Céline; Guevara, Nicolas; Bordone, Olivier; Cardinaud, Bruno; Lebrigand, Kévin; Rios, Géraldine; Santini, Joseph; Franc, Brigitte; Mari, Bernard; Al Ghuzlan, Abir; Vielh, Philippe; Barbry, Pascal; Hofman, Paul

2011-10-01

231

Patients’ perspectives regarding long-term warfarin therapy and the potential transition to new oral anticoagulant therapy  

PubMed Central

Objectives: To examine patients’ perspectives regarding long-term vitamin K antagonist (VKA) therapy and the potential transition to new oral anticoagulants (NOACs) such as dabigatran and rivaroxaban, and to determine if factors such as residential location affect these opinions. Design, setting and participants: Patients on VKA therapy for at least 12 weeks completed a questionnaire specifically designed for the study. They were recruited while attending point-of-care international normalized ratio (INR) testing at six South Australian general practice clinics during the period July–September 2013. Main outcome measures: Opinions of current VKA therapy, level of awareness of NOACs, and ratings of potential benefits and deterrents of transition to NOACs were sought. Results: Data from 290 participants were available for analysis (response rate 95.4%). The majority of the sample (79.5%, 229/288) were either satisfied or very satisfied with current VKA therapy. The mean score for the potential benefits of transition to NOACs was 7.6 (±4.2) out of a possible 20, which was significantly lower than the mean score 10.9 (±4.5) for the perceived deterrents to transition (p < 0.001). Rural patients (82.0%, 82/100) were significantly more likely (p = 0.001) to have not heard of NOACs than metropolitan patients (50.3%, 95/189) and also perceived significant less benefits in a transition to NOACs (p = 0.001). Conclusion: When considering potential transition from VKAs to NOACs it is important for prescribers to consider that some patients, in particular those from a rural location, may not perceive a significant benefit in transitioning or may have particular concerns in this area. PMID:25436104

Gebler-Hughes, Elizabeth S.; Kemp, Linda

2014-01-01

232

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. PMID:20430063

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

2010-01-01

233

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  

Microsoft Academic Search

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

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

2011-01-01

234

Comparison of the clinical behavior of newly diagnosed stages II–IV low-grade serous carcinoma of the ovary with that of serous ovarian tumors of low malignant potential that recur as low-grade serous carcinoma  

Microsoft Academic Search

Background.Serous ovarian tumors of low malignant potential (STLMP) frequently coexist with low-grade serous carcinoma of the ovary (LGSC) and, when they recur, frequently do so as LGSC. The purpose of this study was to compare the outcomes of patients with these two tumor types.

Hyun S. Shvartsman; Charlotte C. Sun; Diane C. Bodurka; Vrinda Mahajan; Marta Crispens; Karen H. Lu; Michael T. Deavers; Anais Malpica; Elvio G. Silva; David M. Gershenson

2007-01-01

235

Limited Potentiation of Blood Pressure in Response to Oral Tyramine by the Anti-Parkinson Brain Selective Multifunctional Monoamine Oxidase-AB Inhibitor, M30  

Microsoft Academic Search

One of the limitations of non-selective monoamine oxidase (MAO) inhibitors as anti-depressant or anti-Parkinson drugs is their\\u000a ability to potentiate the cardiovascular effect of oral tyramine, resulting from inhibition of systemic MAO-A and release\\u000a of noradrenaline. We have investigated the cardiovascular effect of oral tyramine in response to the novel multifunctional,\\u000a brain selective MAO-AB inhibitor, M30 [5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline], and compared it

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

2010-01-01

236

[Malignant pheochromocytoma].  

PubMed

A case of metastatic malignant pheochromocytoma which was operated on is discussed. The benefits derived from the most recent localizing techniques such as CT scan and MIBG scintigraphic scanning are stressed. In the case presented these enabled the adrenal tumor to be detected but also demonstrated the presence of a costal metastasis and two metastases in the axial skeleton. A therapeutic trial with MIBG at doses of 100 mCi per treatment only enabled a survival of a little more than one year to be achieved. PMID:2794545

Pailler, J L; Vicq, P; Jancovici, R; Essoussi, J; Seigneuric, A

1989-01-01

237

Evaluation of amitrole (aminotriazole) for potential carcinogenicity in orally dosed rats, mice, and golden hamsters  

SciTech Connect

Amitrole was evaluated for carcinogenic potential in lifespan studies on Wistar rats, NMRI mice, and golden hamsters. At the start of the studies the animals were 6 weeks old. Amitrole was administered, mixed with pulverized chow, at dietary concentrations of 0, 1, 10, and 100 micrograms/g (ppm). Each treated group and control group consisted of 75 male and 75 female rats and mice and of 76 male and 76 female golden hamsters. Additional animals were used to evaluate the functional state of the thyroid. Somewhat lower body weights, slightly reduced survival times, and transient effects on thyroid function were observed in golden hamsters at 100 ppm. In mice, a slight increase in pituitary gland hyperemias was seen at 100 ppm; also an effect on thyroid function usually occurred at the same concentration. In rats, a very large number of cystic dilatations of follicles in the thyroid at 100 ppm and a dose-unrelated increase in hemorrhages and hyperemias in the pituitary gland were indicative of an effect of amitrole on these organs. The strongest effect of amitrole on thyroid function, as compared to golden hamsters and mice, was seen in rats at 100 ppm. At this concentration a highly increased number of thyroid and pituitary gland tumors was observed in rats. In golden hamsters and mice, no tumor induction was seen.

Steinhoff, D.; Weber, H.; Mohr, U.; Boehme, K.

1983-06-30

238

Immunotherapy for malignant glioma  

PubMed Central

Malignant gliomas (MG) are the most common type of primary malignant brain tumor. Most patients diagnosed with glioblastoma (GBM), the most common and malignant glial tumor, die within 12–15 months. Moreover, conventional treatment, which includes surgery followed by radiation and chemotherapy, can be highly toxic by causing nonspecific damage to healthy brain and other tissues. The shortcomings of standard-of-care have thus created a stimulus for the development of novel therapies that can target central nervous system (CNS)-based tumors specifically and efficiently, while minimizing off-target collateral damage to normal brain. Immunotherapy represents an investigational avenue with the promise of meeting this need, already having demonstrated its potential against B-cell malignancy and solid tumors in clinical trials. T-cell engineering with tumor-specific chimeric antigen receptors (CARs) is one proven approach that aims to redirect autologous patient T-cells to sites of tumor. This platform has evolved dramatically over the past two decades to include an improved construct design, and these modern CARs have only recently been translated into the clinic for brain tumors. We review here emerging immunotherapeutic platforms for the treatment of MG, focusing on the development and application of a CAR-based strategy against GBM. PMID:25722935

Suryadevara, Carter M.; Verla, Terence; Sanchez-Perez, Luis; Reap, Elizabeth A.; Choi, Bryan D.; Fecci, Peter E.; Sampson, John H.

2015-01-01

239

Immunotherapy for malignant glioma.  

PubMed

Malignant gliomas (MG) are the most common type of primary malignant brain tumor. Most patients diagnosed with glioblastoma (GBM), the most common and malignant glial tumor, die within 12-15 months. Moreover, conventional treatment, which includes surgery followed by radiation and chemotherapy, can be highly toxic by causing nonspecific damage to healthy brain and other tissues. The shortcomings of standard-of-care have thus created a stimulus for the development of novel therapies that can target central nervous system (CNS)-based tumors specifically and efficiently, while minimizing off-target collateral damage to normal brain. Immunotherapy represents an investigational avenue with the promise of meeting this need, already having demonstrated its potential against B-cell malignancy and solid tumors in clinical trials. T-cell engineering with tumor-specific chimeric antigen receptors (CARs) is one proven approach that aims to redirect autologous patient T-cells to sites of tumor. This platform has evolved dramatically over the past two decades to include an improved construct design, and these modern CARs have only recently been translated into the clinic for brain tumors. We review here emerging immunotherapeutic platforms for the treatment of MG, focusing on the development and application of a CAR-based strategy against GBM. PMID:25722935

Suryadevara, Carter M; Verla, Terence; Sanchez-Perez, Luis; Reap, Elizabeth A; Choi, Bryan D; Fecci, Peter E; Sampson, John H

2015-01-01

240

Functional analysis of Zyxin in cell migration and invasive potential of oral squamous cell carcinoma cells.  

PubMed

Zyxin is an evolutionarily conserved protein that has been implicated in the regulation of actin assembly and is mainly located at focal adhesions. However, the biological roles of Zyxin in cancer cells are incompletely understood. We analyzed the functions of Zyxin in cell migration and the invasive potential of OSCC. Zyxin expression was examined using eight OSCC cell lines with two different cell morphologies (6 epithelial type and 2 fibroblastic type). To knockdown Zyxin expression, OSCC cells were transfected with Zyxin siRNA and control siRNA. The cell lines were studied by western blot analysis, immunocytochemical analysis and cell migration and invasion assay. Epithelial type OSCC cells showed a high level of E-cadherin expression and a low level of Zyxin expression. N-cadherin as well as Zyxin were strongly expressed in fibroblastic type OSCC cells. Expression levels of LPP and TRIP6, members of the human Zyxin family, did not differ between epithelial type and fibroblastic type. Knockdown of Zyxin expression by siRNA in fibroblastic type OSCC cells was associated with cell morphological changes from spindle (fibroblastic) to polygonal (epithelial) shape and significantly inhibited cell growth as well as cell migration and invasion. Expression levels of Rac1 and Cdc42 were weaker in Zyxin siRNA-treated fibroblastic type OSCC cells than in control siRNA-treated cells, but the expression of RhoA did not differ significantly. Treatment of fibroblastic type OSCC cells with Rac1 inhibitor decreased the expression of Zyxin mRNA and protein. Zyxin is suggested to promote growth, migration and invasiveness of fibroblastic type OSCC cells by upregulating Rac1 and Cdc42. PMID:23292068

Yamamura, Michiyo; Noguchi, Kazuma; Nakano, Yoshiro; Segawa, Emi; Zushi, Yusuke; Takaoka, Kazuki; Kishimoto, Hiromitsu; Hashimoto-Tamaoki, Tomoko; Urade, Masahiro

2013-03-01

241

Telomere homolog oligonucleotides induce apoptosis in malignant but not in normal lymphoid cells: Mechanism and therapeutic potential  

PubMed Central

Human B- or T-cell lymphoma lines and primary murine lymphomas were treated with DNA oligonucleotides homologous to the telomere (TTAGGG repeat; “T-oligo”), either alone or in combination with standard, widely-used anticancer chemotherapeutic agents. T-oligo induces cell cycle arrest and apoptosis in cultured human or murine B or T-lymphoma cell lines and primary tumor cells, but exerts no detectable toxicity on normal human or murine primary lymphocytes. Exposure to T-oligo is hypothesized to mimic exposure of the 3? telomere repeat sequence, activating the ataxia telangiectasia mutated kinase, which phosphorylates downstream effectors such as p53, but effects are not dependent solely on functional p53. T-oligo causes early S-phase arrest and cooperates well with G2- or M-phase-specific anticancer agents; when combined at 1/10th of the conventional dose, vincristine and T-oligo produce greater-than-additive killing of human or murine lymphoma cells (78% of cells undergoing apoptosis after 6 hr vs. 5% of control cells). In mice, 1/10th of the conventional dose of a standard combination of cyclophosphamide, adriamycin, vincristine and prednisone is twice as effective when used in combination with low dose T-oligo. Thus, T-oligo sensitizes tumors to traditional anticancer agents and represents a potentially important new addition to the therapeutic arsenal for aggressive lymphomas. PMID:19003960

Longe, Harold O.; Romesser, Paul B.; Rankin, Andrew M.; Faller, Douglas V.; Eller, Mark S.; Gilchrest, Barbara A.; Denis, Gerald V.

2010-01-01

242

Malignant hyperthermia  

PubMed Central

Malignant hyperthermia (MH) is an uncommon, life-threatening pharmacogenetic disorder of the skeletal muscle. It presents as a hypermetabolic response in susceptible individuals to potent volatile anesthetics with/without depolarizing muscle relaxants; in rare cases, to stress from exertion or heat stress. Susceptibility to malignant hyperthermia (MHS) is inherited as an autosomally dominant trait with variable expression and incomplete penetrance. It is known that the pathophysiology of MH is related to an uncontrolled rise of myoplasmic calcium, which activates biochemical processes resulting in hypermetabolism of the skeletal muscle. In most cases, defects in the ryanodine receptor are responsible for the functional changes of calcium regulation in MH, and more than 300 mutations have been identified in the RYR1 gene, located on chromosome 19q13.1. The classic signs of MH include increase of end-tidal carbon dioxide, tachycardia, skeletal muscle rigidity, tachycardia, hyperthermia and acidosis. Up to now, muscle contracture test is regarded as the gold standard for the diagnosis of MHS though molecular genetic test is used, on a limited basis so far to diagnose MHS. The mortality of MH is dramatically decreased from 70-80% to less than 5%, due to an introduction of dantrolene sodium for treatment of MH, early detection of MH episode using capnography, and the introduction of diagnostic testing for MHS. This review summarizes the clinically essential and important knowledge of MH, and presents new developments in the field. PMID:23198031

2012-01-01

243

Update of the cancer-associated molecular mechanisms in oral lichen planus, a disease with possible premalignant nature.  

PubMed

Oral lichen planus (OLP) is a relatively common inflammatory disease. Several reports of oral squamous cell carcinomas (OSCC) developing in the ground of previous OLP lesions exist in the current medical literature. Hence, there is a debate concerning the possible premalignant nature of OLP. The studies that examined the malignant potential of OLP for many years were mainly observational and were seeking to detect the percentage of OLP patients that developed OSCC. The results of these studies varied significantly with reported percents of malignant transformation of OLP ranging from 0 to 12.5%. In recent years the number of OLP studies that investigate molecular biomarkers identified in cancer is on the rise. This article is an update of the molecular pathways identified in OLP that could be suggestive of a malignant potential of this condition. PMID:22331711

Georgakopoulou, E A; Troupis, T G; Troupis, G; Gorgoulis, V G

2011-01-01

244

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. PMID:22163166

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

2011-01-01

245

Graft-versus-host disease affecting oral cavity. A review.  

PubMed

Graft versus host disease (GVHD) is one of the most frequent and serious complications of hematopoietic stem cell transplantation, and is regarded as the leading cause of late mortality unrelated to the underlying malignant disease. GVHD is an autoimmune and alloimmune disorder that usually affects multiple organs and tissues, and exhibits a variable clinical course. It can manifest in either acute or chronic form. The acute presentation of GVHD is potentially fatal and typically affects the skin, gastrointestinal tract and liver. The chronic form is characterized by the involvement of a number of organs, including the oral cavity. Indeed, the oral cavity may be the only affected location in chronic GVHD. The clinical manifestations of chronic oral GVHD comprise lichenoid lesions, hyperkeratotic plaques and limited oral aperture secondary to sclerosis. The oral condition is usually mild, though moderate to severe erosive and ulcerated lesions may also be seen. The diagnosis is established from the clinical characteristics, though confirmation through biopsy study is sometimes needed. Local corticosteroids are the treatment of choice, offering overall response rates of close to 50%. Extracorporeal photopheresis and systemic corticosteroids in turn constitute second line treatment. Oral chronic GVHD is not considered a determinant factor for patient survival, which is close to 52% five years after diagnosis of the condition. Key words:Chronic graft-versus-host disease, oral chronic graft-versus-host disease, pathogenics, management, survival. PMID:25810826

Margaix-Muńoz, Maria; Bagán, José V; Jiménez, Yolanda; Sarrión, María-Gracia; Poveda-Roda, Rafael

2015-02-01

246

Graft-versus-host disease affecting oral cavity. A review  

PubMed Central

Graft versus host disease (GVHD) is one of the most frequent and serious complications of hematopoietic stem cell transplantation, and is regarded as the leading cause of late mortality unrelated to the underlying malignant disease. GVHD is an autoimmune and alloimmune disorder that usually affects multiple organs and tissues, and exhibits a variable clinical course. It can manifest in either acute or chronic form. The acute presentation of GVHD is potentially fatal and typically affects the skin, gastrointestinal tract and liver. The chronic form is characterized by the involvement of a number of organs, including the oral cavity. Indeed, the oral cavity may be the only affected location in chronic GVHD. The clinical manifestations of chronic oral GVHD comprise lichenoid lesions, hyperkeratotic plaques and limited oral aperture secondary to sclerosis. The oral condition is usually mild, though moderate to severe erosive and ulcerated lesions may also be seen. The diagnosis is established from the clinical characteristics, though confirmation through biopsy study is sometimes needed. Local corticosteroids are the treatment of choice, offering overall response rates of close to 50%. Extracorporeal photopheresis and systemic corticosteroids in turn constitute second line treatment. Oral chronic GVHD is not considered a determinant factor for patient survival, which is close to 52% five years after diagnosis of the condition. Key words:Chronic graft-versus-host disease, oral chronic graft-versus-host disease, pathogenics, management, survival.

Margaix-Muńoz, Maria; Bagán, José V.; Jiménez, Yolanda; Sarrión, María-Gracia; Poveda-Roda, Rafael

2015-01-01

247

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

248

Microwave Ablation of Hepatic Malignancy  

PubMed Central

Microwave ablation is an extremely promising heat-based thermal ablation modality that has particular applicability in treating hepatic malignancies. Microwaves can generate very high temperatures in very short time periods, potentially leading to improved treatment efficiency and larger ablation zones. As the available technology continues to improve, microwave ablation is emerging as a valuable alternative to radiofrequency ablation in the treatment of hepatic malignancies. This article reviews the current state of microwave ablation including technical and clinical considerations. PMID:24436518

Lubner, Meghan G.; Brace, Christopher L.; Ziemlewicz, Tim J.; Hinshaw, J. Louis; Lee, Fred T.

2013-01-01

249

Malignant hemangiopericytoma of the bone  

Microsoft Academic Search

Hemangiopericytoma is a rare vascular tumor of pericyte origin with variable malignant potential. Very rarely, this tumor\\u000a occurs as a primary bone lesion. We present a case of a highly malignant hemangiopericytoma of the proximal tibia. Current\\u000a therapy consists of radical resection of the tumor with postoperative radiation therapy being recommended. Chemotherapy seems\\u000a to be useful in disseminated disease. The

H. R. Dürr; Andreas Nerlich; Andreas Lienemann; Peter Ernst Müller; H. J. Refior

2000-01-01

250

Display of Eimeria tenella EtMic2 protein on the surface of Saccharomyces cerevisiae as a potential oral vaccine against chicken coccidiosis.  

PubMed

S. cerevisiae is generally regarded as safe and benign organism and its surface display system may be used as a unique eukaryotic expression system that is suitable for expressing eukaryotic antigen. In addition to the convenience of vaccine delivery, the yeast cell wall has been shown to enhance the innate immunity when immunized with the yeast live oral vaccine. In the present study, we expressed the chicken coccidian E. tenella EtMic2, a microneme protein, on the surface of the S. cerevisiae and evaluated it as a potential oral vaccine for chicken against E. tenella challenge. The protective efficacy against a homologous challenge was evaluated by body weight gains, lesion scores and fecal oocyst shedding. The results showed that the live oral vaccine can improve weight gains, reduced cecal pathology and lower oocyst fecal shedding compared with non immunized controls. In addition, the yeast oral vaccine could stimulate humoral as well as cell mediate immune responses. These results suggested that EtMic2 displayed on the cell surface of S. cerevisiae could be used as potential live vaccine against chicken coccidiosis. PMID:24530147

Sun, Hui; Wang, Longjiang; Wang, Tiantian; Zhang, Jie; Liu, Qing; Chen, Peipei; Chen, Zhengtao; Wang, Fangkun; Li, Hongmei; Xiao, Yihong; Zhao, Xiaomin

2014-04-01

251

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

252

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

PubMed

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

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

2012-10-01

253

Treatment Options for Malignant Mesothelioma  

MedlinePLUS

... Dictionary Search for Clinical Trials NCI Publications Espańol Malignant Mesothelioma Treatment (PDQ®) Treatment Options for Malignant Mesothelioma Localized Malignant Mesothelioma (Stage I) If malignant ...

254

Radiosensitization by fullerene-C60 dissolved in squalene on human malignant melanoma through lipid peroxidation and enhanced mitochondrial membrane potential  

NASA Astrophysics Data System (ADS)

We examined fullerene-C60 dissolved in squalene (C60/Sqe) for the ability to potentiate the radiosensitization under X-ray irradiation on human malignant melanoma HMV-II cells, which were treated with C60/Sqe and thereafter irradiated with X-ray. The cell proliferation for C60/Sqe was inhibited more markedly than for Sqe alone. Meanwhile, cell proliferation was almost unaltered for C60/squalane (Sqa) or Sqa, a hydrogenated form of Sqe, as compared to no-additive control. Thus radiosensitization of C60/Sqe is attributed to peroxidation of unsaturated bonds of squalene by X-ray-excited C60 in contrast to squalane. The fluorescence images of HMV-II cells stained with Rhodamine123, an indicator for mitochondrial membrane potential, were monitored for 6 h after X-ray irradiation. C60/Sqe obviously exhibited more augmented fluorescence intensity on perinuclear region of HMV-II cells than Sqe alone. TBARS assay showed that the lipid peroxidation level as malondialdehyde-equivalent increased by combination of C60/Sqe and X-ray dose-dependently on X-ray doses. C60/Sqe exhibited lipid peroxidation more markedly by 1.2-fold than Sqe alone. Thus the level of lipid peroxidation of squalene was sufficiently higher in C60/Sqe than in Sqe in the absence of C60 under X-ray irradiation, suggesting the combination of C60/Sqe and X-ray irradiation induced radiosensitization on HMV-II cells by peroxidation of absorbed Sqe in mitochondrial membrane via oxidative stress mediated by fullerene-C60.

Kato, Shinya; Kimura, Masatsugu; Miwa, Nobuhiko

2014-04-01

255

Allelic loss at 19q12 and Xq11-12 predict an adverse clinical outcome in patients with mucinous ovarian tumours of low malignant potential.  

PubMed

Ovarian tumours of low malignant potential (LMP) are intermediate between adenomas and ovarian carcinomas. These tumours are often associated with a significantly better prognosis than ovarian carcinomas. However, a subset of these tumours can progress and become lethal. In order to seek sensitive diagnostic tools for monitoring patients after surgical operation, we performed a genome-wide scan for loss of heterozygosity (LOH) in 41 mucinous LMPs using 91 polymorphic microsatellite markers at an average interval of 50 cM across all of the human chromosomes and 25 LOH markers reportedly associated with ovarian carcinoma. In addition, we assessed whether clinicopathological parameters, microvessel density, Ki-67 labeling index, apoptotic index or p53 overexpression would be useful for predicting the postoperative outcome of LMP patients. Of the 116 markers examined, 19q12 and Xq11-12 showed significant correlation between postoperative progression-free survival time and LOH status (P<0.05). Patients with a high Ki-67 labeling index had a significantly poorer progression-free survival time than those with lower levels (P=0.042). Other clinicopathological factors and immunohistochemical analysis had no correlation with progression-free survival time in this series of patients. When the combination of LOH at 19q12 and/or Xq11-12 was assessed using Cox's regression analysis, patients with tumours that showed LOH at these positions were at greatest risk of progression (P=0.0073). These findings suggest that the identification of LOH at 19q12 and/or Xq11-12 in former mucinous LMP sites should alert the clinician to the presence of a potentially aggressive lesion in the coelomic epithelium, even if a distinction between second primary tumours or recurrence could not be determined. PMID:15026802

Nakayama, K; Takebayashi, Y; Hata, K; Fujiwaki, R; Iida, K; Fukumoto, M; Miyazaki, K

2004-03-22

256

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. PMID:23450083

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

2013-01-01

257

The application of vizilite in oral cancer.  

PubMed

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

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

2013-01-01

258

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

259

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. PMID:23856774

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

2013-01-01

260

A case report of neuroleptic malignant syndrome.  

PubMed

A 32-year-old male patient with a history of treatment resistant paranoid schizophrenia developed neuroleptic malignant syndrome (NMS) during changeover of his antipsychotic medication from zuclopenthixol depot to clozapine. This case highlights the difficulties of cross-tapering two antipsychotics-that is, converting from a typical depot medication to an oral atypical antipsychotic. PMID:21686818

Kuchibatla, Shankar Srinivas; Cheema, Sofia Akram; Chakravarthy, Kripa S; Sayeh, Hany George El

2009-01-01

261

Generation of specific effector and memory T cells with gut- and secondary lymphoid tissue- homing potential by oral attenuated CVD 909 typhoid vaccine in humans  

Microsoft Academic Search

Induction of effective memory T cells is likely to be critical to the level and duration of protection elicited by novel live oral typhoid vaccines. Using cells from volunteers who ingested Salmonella Typhi vaccine strain CVD 909, we characterized the induction of interferon (IFN)-?-secreting central (TCM, CD45RO+CD62L+) and effector (TEM, CD45RO+CD62L?) memory T populations, and their gut-homing potential based on

R Wahid; R Salerno-Gonçalves; C O Tacket; M M Levine; M B Sztein

2008-01-01

262

Adjuvant potential of low dose all-trans retinoic acid during oral typhoid vaccination in Zambian men.  

PubMed

There is an urgent need to identify ways of enhancing the mucosal immune response to oral vaccines. Rotavirus vaccine protection is much lower in Africa and Asia than in industrialized countries, and no oral vaccine has efficacy approaching the best systemic vaccines. All-trans retinoic acid (ATRA) up-regulates expression of ?4?7 integrin and CCR9 on lymphocytes in laboratory animals, increasing their gut tropism. The aim of this study was to establish the feasibility of using ATRA as an oral adjuvant for oral typhoid vaccination. In order to establish that standard doses of oral ATRA can achieve serum concentrations greater than 10?nmol/l, we measured ATRA, 9-cis and 13-cis retinoic acid in serum of 14 male volunteers before and 3?h after 10?mg ATRA. We then evaluated the effect of 10?mg ATRA given 1?h before, and for 7 days following, oral typhoid vaccine in eight men, and in 24 men given various control interventions. We measured immunoglobulin (Ig)A directed against lipopolysaccharide (LPS)and protein preparations of vaccine antigens in whole gut lavage fluid (WGLF) and both IgA and IgG in serum, 1 day prior to vaccination and on day 14. Median [interquartile range (IQR)] C(max) was 26·2 (11·7-39·5) nmol/l, with no evidence of cumulation over 8 days. No adverse events were observed. Specific IgA responses to LPS (P?=?0·02) and protein (P?=?0·04) were enhanced in WGLF, but no effect was seen on IgA or IgG in serum. ATRA was well absorbed, well tolerated and may be a promising candidate oral adjuvant. PMID:24237035

Lisulo, M M; Kapulu, M C; Banda, R; Sinkala, E; Kayamba, V; Sianongo, S; Kelly, P

2014-03-01

263

Adjuvant potential of low dose all-trans retinoic acid during oral typhoid vaccination in Zambian men  

PubMed Central

There is an urgent need to identify ways of enhancing the mucosal immune response to oral vaccines. Rotavirus vaccine protection is much lower in Africa and Asia than in industrialized countries, and no oral vaccine has efficacy approaching the best systemic vaccines. All-trans retinoic acid (ATRA) up-regulates expression of ?4?7 integrin and CCR9 on lymphocytes in laboratory animals, increasing their gut tropism. The aim of this study was to establish the feasibility of using ATRA as an oral adjuvant for oral typhoid vaccination. In order to establish that standard doses of oral ATRA can achieve serum concentrations greater than 10?nmol/l, we measured ATRA, 9-cis and 13-cis retinoic acid in serum of 14 male volunteers before and 3?h after 10?mg ATRA. We then evaluated the effect of 10?mg ATRA given 1?h before, and for 7 days following, oral typhoid vaccine in eight men, and in 24 men given various control interventions. We measured immunoglobulin (Ig)A directed against lipopolysaccharide (LPS)and protein preparations of vaccine antigens in whole gut lavage fluid (WGLF) and both IgA and IgG in serum, 1 day prior to vaccination and on day 14. Median [interquartile range (IQR)] Cmax was 26·2 (11·7–39·5) nmol/l, with no evidence of cumulation over 8 days. No adverse events were observed. Specific IgA responses to LPS (P?=?0·02) and protein (P?=?0·04) were enhanced in WGLF, but no effect was seen on IgA or IgG in serum. ATRA was well absorbed, well tolerated and may be a promising candidate oral adjuvant. PMID:24237035

Lisulo, M M; Kapulu, M C; Banda, R; Sinkala, E; Kayamba, V; Sianongo, S; Kelly, P

2014-01-01

264

Intrathecal combination of ziconotide and morphine for refractory malignant pain: A rapidly acting and effective choice  

Microsoft Academic Search

Ziconotide is a nonopioid intrathecal analgesic drug used to manage moderate to severe chronic pain. The aim of this work is to assess the safety and efficacy of intrathecal (IT) combination of ziconotide and morphine in malignant pain refractory to high doses of oral opioids. Patients with malignant pain refractory to high oral opioids doses with a mean visual analogue

Ilaria Alicino; Mariateresa Giglio; Fabio Manca; Francesco Bruno; Filomena Puntillo

265

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 44.2 nm 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

266

Evaluation of the Antimicrobial, Antioxidant, and Anti-Inflammatory Activities of Hydroxychavicol for Its Potential Use as an Oral Care Agent?  

PubMed Central

Hydroxychavicol isolated from the chloroform extraction of aqueous extract of Piper betle leaves showed inhibitory activity against oral cavity pathogens. It exhibited an inhibitory effect on all of the oral cavity pathogens tested (MICs of 62.5 to 500 ?g/ml) with a minimal bactericidal concentration that was twofold greater than the inhibitory concentration. Hydroxychavicol exhibited concentration-dependent killing of Streptococcus mutans ATCC 25175 up to 4× MIC and also prevented the formation of water-insoluble glucan. Interestingly, hydroxychavicol exhibited an extended postantibiotic effect of 6 to 7 h and prevented the emergence of mutants of S. mutans ATCC 25175 and Actinomyces viscosus ATCC 15987 at 2× MIC. Furthermore, it also inhibited the growth of biofilms generated by S. mutans and A. viscosus and reduced the preformed biofilms by these bacteria. Increased uptake of propidium iodide by hydroxychavicol-treated cells of S. mutans and A. viscosus indicated that hydroxychavicol probably works through the disruption of the permeability barrier of microbial membrane structures. Hydroxychavicol also exhibited potent antioxidant and anti-inflammatory activities. This was evident from its concentration-dependent inhibition of lipid peroxidation and significant suppression of tumor necrosis factor alpha expression in human neutrophils. Its efficacy against adherent cells of S. mutans in water-insoluble glucan in the presence of sucrose suggests that hydroxychavicol would be a useful compound for the development of antibacterial agents against oral pathogens and that it has great potential for use in mouthwash for preventing and treating oral infections. PMID:18573934

Sharma, Sandeep; Khan, Inshad Ali; Ali, Intzar; Ali, Furqan; Kumar, Manoj; Kumar, Ashwani; Johri, Rakesh Kamal; Abdullah, Sheikh Tasduq; Bani, Sarang; Pandey, Anjali; Suri, Krishan Avtar; Gupta, Bishan Datt; Satti, Naresh Kumar; Dutt, Prabhu; Qazi, Ghulam Nabi

2009-01-01

267

Induction of parathyroid hormone-related peptide by the Ras oncogene: role of Ras farnesylation inhibitors as potential therapeutic agents for hypercalcemia of malignancy.  

PubMed

Parathyroid hormone related peptide (PTHRP) is the major causal agent in the syndrome of malignancy-associated hypercalcemia (MAH). Several studies have shown that PTHRP production is increased in response to growth factors and oncogenes, such as Tpr-Met, that are associated with the tyrosine kinase signaling pathway. Using site-directed mutagenesis of Tpr-Met and chemical inhibitors of phosphotidylinositol-3 kinase and Ras isoprenylation, we demonstrated previously that induction of PTHRP is mediated via the Ras signaling pathway. In the present study, we have directly investigated the role of the Ras oncogene in MAH. As a model system, we used Fisher rat 3T3 fibroblasts stably transfected with a Ras oncogene (Ras-3T3). Ras transfection enhanced PTHRP production 5-10-fold in these cells, and inoculation of this cell line into nude mice led to the development of hypercalcemia within 2 weeks. We used this system to evaluate the effect of a potent inhibitor of Ras processing, B-1086, on cell growth, PTHRP production, plasma calcium, and tumor growth. Treatment of Ras-3T3 cells in vitro with B-1086 at 0.1-10 microg/ml produced a significant reduction in PTHRP mRNA expression and PTHRP secretion and a significant decrease in cell proliferation. Treatment in vivo of BALB/c/nu/nu mice bearing Ras-3T3 tumors with B-1086 resulted in a significant inhibition in tumor growth. In addition, this treatment produced near normalization of serum Ca2+, a significant decrease in plasma PTHRP, and a reduction in tumoral PTHRP mRNA levels. These results show that the Ras pathway is involved in PTHRP production by tumors, identifies Ras as a potential target for treatment of MAH, and demonstrates Ras processing inhibitors as candidate therapeutic agents against this syndrome. PMID:9377563

Aklilu, F; Park, M; Goltzman, D; Rabbani, S A

1997-10-15

268

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

PubMed Central

Despite recent advances in treatment, malignant pleural mesothelioma (MPM) remains a deadly disease. Targeted therapy generated broad interests and is highly expected for the treatment of MPM, yet promising preclinical results have not been translated into substantial clinical benefits for the patients. In this study, we tried to identify the genes which play functional roles in cell migration as well as to test whether they can be used as novel targets for molecular targeted therapy for MPM in preclinical model. In our study, pregnancy-associated plasma protein A (PAPPA) was identified as a gene whose expression level is correlated with MPM cell migration by correlation analysis combining MPM cell migration ability and their gene expression profiles. Highly migratory cells were selected from MPM cell lines, MSTO-211H, NCI-H290 and EHMES-1 in vitro and up-regulation of PAPPA in these cells were confirmed. In vitro, PAPPA was demonstrated to stimulate the MPM cell migration via cleavage of insulin-like growth factor-binding protein-4 and subsequent release of IGF-1. Gene silencing of PAPPA in MPM cells led to reduced migration, invasion and proliferation. Furthermore, PAPPA shRNA transfected NCI-H290 when orthotopically inoculated into pleural cavity of severe combined immunodeficiency recipient mice, failed to develop tumors and produce bloody pleural effusion as control shRNA transfected cells did. Our study suggests that PAPPA plays a functional role in promoting MPM cell migration and it might serve as a potential therapeutic target for the treatment of MPM. PMID:23896451

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

2013-01-01

269

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

270

Chapter 10: Sinonasal malignancies.  

PubMed

Malignant tumors of the sinonasal tract are uncommon tumors of the head and neck. Patients often present in the later years of life with unilateral symptoms and potential involvement of nearby structures such as the orbit, brain, or cranial nerves. Presenting symptoms are similar to patients suffering from inflammatory sinonasal disease and thus early diagnosis relies heavily on a high clinical suspicion. There are established risk factors based on exposure to the by-products of woodworking, metal, textile, and leather industries. Sinonasal malignancies are generally divided into those of epithelial origin (squamous cell carcinoma, adenocarcinoma, and adenoid cystic carcinoma) and nonepithelial origin (olfactory neuroblastoma, chondrosarcoma, and mucosal melanoma). Accurate histopathology confirmation and staging of the tumor is critical prior to making treatment decisions. Both computed tomography and magnetic resonance imaging are required to accurately determine the extent of local disease. Treatment is based on multimodality therapy, primarily surgical excision, and postoperative radiotherapy. This article reviews the classification of malignant tumors of the paranasal sinuses, their clinical presentation, relevant diagnostic investigations, and the principals of therapy and management. PMID:23711038

Harvey, Richard J; Dalgorf, Dustin M

2013-01-01

271

[Soft tissue pathologies of the oral cavity].  

PubMed

The most frequent form of neoplasia in the oral cavity is the squamous cell carcinoma (about 90% of cases) representing the 3-5% of all malignant tumors with about 56% of mortality rate, at 5 years from the diagnosis. In general, the neoplastic disease is now unanimly considered as a multifactorial and multiphasic pathology. Multiphasic since the carcinogenic process consists in the cellular capacity to acquire oncological potentialities through several stages such as: moltiplication (a), transmission (b) of malignity caracteristics to progenic cells, invasivity (c), capacity to give metastasis (d) and also resistance to chemiotherapy. Multifactorial since in the onset of the disease intrinsic and extrinsic factors are certainly involved. In the carcinogenic process of CCS a high percentage has been noticed of loss of heterozygosity (LOH) in the short arm (P) of cromosoms 3 and 9, which contains the tumor-suppressor genes p53 and DDC (Deleted in colon rectal cancer). In the onset of VADS carcinoma and in particular of oral CCS, it has also been formulated the hypothesis of an intrinsic genetic factor (Llewellyn et al., 2001) between patients, also young, who present the neoplasia even trough they have never been exposed to extrinsic risk factors such as smoke and alcohol. Since part of patients with oral CCS do not always refer a common risk factors history as possible extrinsic neoplasia causes, it has been formulated the hypothesis that some viral infections, for their oncogenic capacity, could be the main ethiological factors predisposing to this neoplasia. The HPV are responsible, either in the oral cavity or on the epidermis, for benign proliferations such as: Verruca Vulgaris, Condyloma Acuminatum, Focal Epithelial Hyperplasia, Squamous Cell Papillomas, but also lesions that are potentially or certainly malignant such as CCS and Verrucous Carcinoma. The molecular analysis performed show that proteins produced from E6 and E7 portions of viral genoma (HPV 16-18) interfer and degrade proteins p53 and pRb produced by tumor suppressor genes (TSg). Recently, thanks to new molecular biology techniques, several authors are studying potentially neoplastic lesions, in order to better understand the association with HPV. PMID:12686915

Margotta, V; Capogreco, M

2003-01-01

272

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

PubMed Central

Polycyclic aromatic hydrocarbons (PAHs) are believed to be among the causative agents for lung cancer in smokers. PAHs require metabolic activation for carcinogenicity. One pathway produces diol epoxides that react with DNA, causing mutations. Because diol epoxides are converted to tetraols, quantitation of tetraols can potentially be used to identify smokers who may be at higher risk for lung cancer. Our approach uses [D10]phenanthrene, a labeled version of phenanthrene, a noncarcinogenic PAH structurally analogous to carcinogenic PAH. Although smokers are exposed to PAH by inhalation, oral dosing would be more practical for phenotyping studies. Therefore, we investigated [D10]phenanthrene metabolism in smokers after administration by inhalation in cigarette smoke or orally. Sixteen smokers received 10 ?g of [D10]phenanthrene in a cigarette or orally. Plasma and urine samples were analyzed for [D10]r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene ([D10]PheT), the major end product of the diol epoxide pathway, by gas chromatography-negative ion chemical ionization-tandem mass spectrometry. The ratios of [D10]PheT (oral dosing/inhalation) in 15 smokers were 1.03 ± 0.32 and 1.02 ± 0.35, based on plasma area under the concentration-time curve (0-?) and total 48-h urinary excretion, respectively. Overall, there was no significant difference in the extent of [D10]PheT formation after the two different routes of exposure in smokers. A large interindividual variation in [D10]PheT formation was observed. These results demonstrate that the level of [D10]PheT in urine after oral dosing of [D10]phenanthrene can be used to assess individual capacity of PAH metabolism by the diol epoxide pathway. PMID:21515812

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

2011-01-01

273

Expression of the EPHB4 receptor tyrosine kinase in head and neck and renal malignancies—implications for solid tumors and potential for therapeutic inhibition  

PubMed Central

Solid malignancies are often characterized by overexpression of various receptor tyrosine kinases (RTKs) against which many targeted therapies are currently in use and in active development. EPHB4 has recently emerged as a frequently overexpressed RTK in many types of cancer. Here, we demonstrate expression patterns of EPHB4 in two solid malignancies, squamous cell carcinoma of the head and neck (HNSCC) and renal cell carcinoma (RCC), by immunohistochemical analysis. We demonstrate the first association between EPHB4 expression and progression of HNSCC from normal tissue to dysplasia and to cancer. Interestingly, most RCC subtypes exhibited expression patterns that were opposite from that found in HNSCC, possibly owing to their unique biology and high degree of organ and tumor vasculature. Taken together, these results suggest a possible role for EPHB4 as a therapeutic target in these malignancies. PMID:25391996

Ferguson, Benjamin D.; Tretiakova, Maria S.; Lingen, Mark W.; Gill, Parkash S.; Salgia, Ravi

2014-01-01

274

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

275

Malignant hyperthermia  

PubMed Central

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered. Thanks to the dramatic progress in understanding the clinical manifestation and pathophysiology of the syndrome, the mortality from MH has dropped from over 80% thirty years ago to less than 5%. PMID:17456235

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

2007-01-01

276

Neuraminidase-producing oral mitis group streptococci potentially contribute to influenza viral infection and reduction in antiviral efficacy of zanamivir.  

PubMed

Influenza is a serious respiratory disease among immunocompromised individuals, such as the elderly, and its prevention is an urgent social issue. Influenza viruses rely on neuraminidase (NA) activity to release progeny viruses from infected cells and spreading the infection. NA is, therefore, an important target of anti-influenza drugs. A causal relationship between bacteria and influenza virus infection has not yet been established, however, a positive correlation between them has been reported. Thus, in this study, we examined the biological effects of oral mitis group streptococci, which are predominant constituents of human oral florae, on the release of influenza viruses. Among them, Streptococcus oralis ATCC 10557 and Streptococcus mitis ATCC 6249 were found to exhibit NA activity and their culture supernatants promoted the release of influenza virus and cell-to-cell spread of the infection. In addition, culture supernatants of these NA-producing oral bacteria increased viral M1 protein expression levels and cellular ERK activation. These effects were not observed with culture supernatants of Streptococcus sanguinis ATCC 10556 which lacks the ability to produce NA. Although the NA inhibitor zanamivir suppressed the release of progeny viruses from the infected cells, the viral release was restored upon the addition of culture supernatants of NA-producing S. oralis ATCC 10557 or S. mitis ATCC 6249. These findings suggest that an increase in the number of NA-producing oral bacteria could elevate the risk of and exacerbate the influenza infection, hampering the efficacy of viral NA inhibitor drugs. PMID:25001578

Kamio, Noriaki; Imai, Kenichi; Shimizu, Kazufumi; Cueno, Marni E; Tamura, Muneaki; Saito, Yuko; Ochiai, Kuniyasu

2015-01-01

277

Primary Malignant Melanoma of Maxilla: Report of a Case with Discussion  

PubMed Central

Primary oral malignant melanoma, very rare neoplasm of melanocytic origin, usually presents as a bluish black to tan-brown colored lesion Which is accounting for 0.2 to 8% of all melanomas, 1.6% of all head and neck malignancies, and 0.5% of all oral neoplasia. In general, the prognosis of oral melanoma is poor and worse than that of cutaneous melanoma. Here a case of oral malignant melanoma is presented, which was undetected during the first visit to a dental clinic. When a simple oral surgical treatment was carried out in that region, it resulted in the appearance of a massive pigmented lesion which was histopathologically diagnosed as malignant melanoma. This paper is presented to reemphasize the fact that any pigmented lesion in the oral cavity should be viewed with suspicion and proper investigation (biopsy) should be carried out to rule out any untoward experiences later. PMID:25642350

Rani, G. Shirisha; Kumar, T. Vinay; Begum, Md Rezwana; Priya Srinivasan, Anu

2014-01-01

278

Oral myiasis.  

PubMed

Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy. PMID:25709196

Saravanan, Thalaimalai; Mohan, Mathan A; Thinakaran, Meera; Ahammed, Saneem

2015-01-01

279

Oral Myiasis  

PubMed Central

Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy. PMID:25709196

Saravanan, Thalaimalai; Mohan, Mathan A; Thinakaran, Meera; Ahammed, Saneem

2015-01-01

280

Significance of Peritoneal Washing Cytopathology in Ovarian Carcinomas and Tumors of Low Malignant Potential: A Quality Control Study with Literature Review  

Microsoft Academic Search

Objective: The author evaluated a consecutive group of peritoneal washings (PWs) performed in the evaluation of adnexal masses to determine whether the conventional histopathologic prognostic parameters significantly affect the tumor detection rate using this procedure. Study Design: Cytopathologic reports from all PWs performed over a 13-year (1996–2008) period in the evaluation of malignant and borderline ovarian tumors were reviewed and

Sevgiye Kaçar Özkara

2011-01-01

281

Activated networking of platelet activating factor receptor and FAK\\/STAT1 induces malignant potential in BRCA1-mutant at-risk ovarian epithelium  

Microsoft Academic Search

OBJECTIVES: It is essential to understand the molecular basis of ovarian cancer etiology and tumor development to provide more effective preventive and therapeutic approaches to reduce mortality. Particularly, the molecular targets and pathways involved in early malignant transformation are still not clear. Pro-inflammatory lipids and pathways have been reported to play significant roles in ovarian cancer progression and metastasis. The

Lifang Zhang; Dan Wang; Wei Jiang; Dale Edwards; Weiliang Qiu; Lisa M Barroilhet; Jung-hyun Rho; Lianjin Jin; Vanitha Seethappan; Allison Vitonis; Jianliu Wang; Samuel C Mok; Christopher Crum; Daniel W Cramer; Bin Ye

2010-01-01

282

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. PMID:20041058

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

2009-01-01

283

Effects of amitriptyline and intra-oral device appliance on clinical and laser-evoked potentials features in chronic tension-type headache.  

PubMed

In the present study, we examined clinical and laser-evoked potentials (LEP) features in two groups of chronic tension-type headache (CTTH) patients treated with two different approaches: intra-oral appliance of prosthesis, aiming to reduce muscular tenderness, and 10 mg daily amitriptyline. Eighteen patients suffering from CTTH (IHS, 2004) participated in the study. We performed a basal evaluation of clinical features and LEPs in all patients (T0) vs. 12 age- and sex-matched controls; successively, patients were randomly assigned to a two-month treatment by amitriptyline or intra-oral device appliance. The later LEPs, especially the P2 component, were significantly increased in amplitude in the CTTH group. Both the intra-oral prosthesis and amitriptyline significantly reduced headache frequency. Total Tenderness Score was significantly reduced in the group treated by the prosthesis. The amplitude of P2 response elicited by stimulation of pericranial zones showed a reduction after amitriptyline treatment. The results of this study may confirm that pericranial tenderness is primarily a phenomenon initiating a self-perpetuating circuit, favoured by central sensitisation at the level of the cortical nociceptive areas devoted to the attentive and emotive compounds of pain. Both the interventions at the peripheral and central levels may interrupt this reverberating circuit, improving the outcome of headache. PMID:15926017

de Tommaso, M; Shevel, E; Libro, G; Guido, M; Di Venere, D; Genco, S; Monetti, C; Serpino, C; Barile, G; Lamberti, P; Livrea, P

2005-05-01

284

The New Orality: Oral Characteristics of Computer-Mediated Communication.  

ERIC Educational Resources Information Center

Considers the characteristics of orality and literacy developed in the work of scholars such as Walter Ong to consider computer-mediated communication (CMC) as the potential site of a "new orality" which is neither purely oral or literate. Notes that the medium of CMC is writing, which has traditionally represented the "literate," while the…

Ferris, Sharmila Pixy; Montgomery, Maureen

1996-01-01

285

Anatomy-Based Algorithms for Detecting Oral Cancer Using Reflectance and Fluorescence Spectroscopy  

E-print Network

OBJECTIVES: We used reflectance and fluorescence spectroscopy to noninvasively and quantitatively distinguish benign from dysplastic/malignant oral lesions. We designed diagnostic algorithms to account for differences in ...

McGee, Sasha

286

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. PMID:24353702

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

2013-01-01

287

Identification of miRNA103 in the Cellular Fraction of Human Peripheral Blood as a Potential Biomarker for Malignant Mesothelioma – A Pilot Study  

Microsoft Academic Search

BackgroundTo 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

Daniel G. Weber; Georg Johnen; Oleksandr Bryk; Karl-Heinz Jöckel; Thomas Brüning

2012-01-01

288

Oral nicotinamide and actinic keratosis: a supplement success story.  

PubMed

Nicotinamide has shown potential as a safe and effective intervention for the prevention of malignant and premalignant skin lesions. Recent studies have shown that nicotinamide, in both oral and topical forms, is able to prevent ultraviolet-induced immunosuppression in humans [1,2,3] and mice [4,5]. Immunosuppression is a known factor for the progression of premalignant lesions, such as actinic keratosis [6]. Murine studies have shown that nicotinamide is also able to protect against photocarcinogenesis [4,5]. Preliminary human studies suggest that nicotinamide may help prevent skin cancers and enhance the regression of actinic keratoses. PMID:25561219

Kim, Burcu; Halliday, Gary M; Damian, Diona L

2015-01-01

289

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

PubMed Central

Background Oral malignancy is a major global health problem. Besides the main risk factors of tobacco, smoking and alcohol, infection by human papillomavirus (HPV) and genetic alterations are likely to play an important role in these lesions. The purpose of this study was to compare the efficacy of HC-II assay and PCR for the detection of specific HPV type (HPV 16 E6) in OSMF and OSCC cases as well as find out the prevalence of the high risk HPV (HR-HPV) in these lesions. Methods and materials Four hundred and thirty patients of the potentially malignant and malignant oral lesions were taken from the Department of Otorhinolaryngology, Moti Lal Nehru Medical College, Allahabad, India from Sept 2007-March 2010. Of which 208 cases were oral submucous fibrosis (OSMF) and 222 cases were oral squamous cell carcinoma (OSCC). The HC-II assay and PCR were used for the detection of HR-HPV DNA. Result The overall prevalence of HR-HPV 16 E6 DNA positivity was nearly 26% by PCR and 27.4% by the HC-II assay in case of potentially malignant disorder of the oral lesions such as OSMF. However, in case of malignant oral lesions such as OSCC, 32.4% HPV 16 E6 positive by PCR and 31.4% by the HC-II assay. In case of OSMF, the two test gave concordant result for 42 positive samples and 154 negative samples, with an overall level of agreement of 85.4% (Cohen's kappa = 66.83%, 95% CI 0.553-0.783). The sensitivity and specificity of the test were 73.7% and 92.05% (p < 0.00). In case of OSCC, the two test gave concordant result for 61 positive samples and 152 negative samples, with an overall level of agreement of 88.3% (Cohen's kappa = 79.29, 95% CI 0.769-0.939) and the sensitivity and specificity of the test were 87.14% and 92.76% (p < 0.00). Conclusion This study concluded that slight difference was found between the positivity rate of HR-HPV infection detected by the HC-II and PCR assay in OSMF and OSCC cases and the HC II assay seemed to have better sensitivity in case of OSCC. PMID:20863370

2010-01-01

290

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 ...

291

The Cultivable Human Oral Gluten-Degrading Microbiome and its Potential Implications in Celiac Disease and Gluten Sensitivity  

PubMed Central

Celiac disease is characterized by intestinal inflammation caused by gluten, proteins which are widely contained in the Western diet. Mammalian digestive enzymes are only partly capable of cleaving gluten, and fragments remain that induce toxic responses in celiac patients. We found that the oral microbiome is a novel and rich source of gluten degrading enzymes. Here we report on the isolation and characterization of the cultivable resident oral microbes that are capable of cleaving gluten, with special emphasis on its immunogenic domains. Bacteria were obtained by a selective culturing approach and enzyme activities were characterised by: 1) Hydrolysis of paranitroanilide-derivatised gliadin-derived tripeptide substrates; 2) Gliadin degradation in-gel (gliadin zymography); 3) Gliadin degradation in solution; 4) Proteolysis of the highly immunogenic ?-gliadin-derived 33-mer. For select strains pH activity profiles were determined. The culturing strategy yielded 87 aerobic and 63 anaerobic strains. Species with activity in at least two of the four assays were typed as: Rothia mucilaginosa HOT-681, Rothia aeria HOT-188, Actinomyces odontolyticus HOT-701, Streptococcus mitis HOT-677, Streptococcus sp. HOT-071, Neisseria mucosa HOT-682 and Capnocytophaga sputigena HOT-775, with Rothia species being active in all four assays. Cleavage specificities and substrate preferences differed among the strains identified. The approximate molecular weights of the enzymes were ~75 kD (Rothia spp.), ~60 kD (A. odontolyticus) and ~150 kD (Streptococcus spp.). In conclusion, this study identified new gluten-degrading microorganisms in the upper gastro-intestinal tract. A cocktail of the most active oral bacteria, or their isolated enzymes, may offer promising new treatment modalities for celiac disease. PMID:23714165

Fernandez-Feo, Martin; Wei, Guoxian; Blumenkranz, Gabriel; Dewhirst, Floyd E.; Schuppan, Detlef; Oppenheim, Frank G.; Helmerhorst, Eva J.

2013-01-01

292

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

293

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. PMID:24088270

2013-01-01

294

Advances in oral therapy for multiple myeloma.  

PubMed

Conventional intravenous chemotherapy regimens are toxic, cumbersome, and negatively affect patients' quality of life, with oral treatment preferable to most patients with cancer. Multiple myeloma is the second most common haematological malignant disease, but cannot be cured with conventional and high-dose chemotherapy. New oral treatments that target myeloma cells or bone marrow are being developed that are highly effective yet have low toxic effects, such as the immunomodulatory drugs thalidomide and lenalidomide. Several treatments in early development have shown antimyeloma activity, including: CHIR-258, which inhibits fibroblast growth factor receptor 3; NVP-ADW742, which inhibits insulin-like growth factor receptor 1; and PTK787, which inhibits vascular endothelial growth factor. Additional drugs aimed at switching off silenced genes include histone deacetylase inhibitors. The availability of these various oral treatments is hoped to improve regimens that, if used sequentially or in combination, offer the potential of making multiple myeloma a chronic disease, thereby extending patients' lifespans and improving quality of life. PMID:16574547

Morgan, Gareth J; Krishnan, Biju; Jenner, Matthew; Davies, Faith E

2006-04-01

295

Molecular alterations in the tumor suppressor gene WWOX in oral leukoplakias  

PubMed Central

Summary Oral leukoplakia is the most prevalent and potentially malignant disorder of the oral mucosa. Previous studies have demonstrated that molecular changes of the WWOX gene (WW-domain containing oxidoreductase), a candidate tumor suppressor gene located at 16q23.3–24.1 that spans FRA16D, the second most common fragile site, are present in several malignant neoplasias, including oral squamous cell carcinoma. In this report, the role of the WWOX gene was investigated in 23 cases of oral leukoplakias. Using nested RT-PCR and immunohistochemistry, altered mRNA transcription and/or reduced Wwox protein expression was observed in 35% of the lesions when compared with normal mucosa. The majority of lesions (4/6) with altered transcripts had a reduction in the expression of Wwox protein. Although normal WWOX expression was found in some lesions with dysplasia, all lesions with WWOX mRNA and/or protein expression showed histological evidence of dysplasia and none of the cases without dysplasia presented this alteration. These results show that the WWOX gene alteration is an early genetic alteration and may contribute to oral carcinogenesis. PMID:18061530

Pimenta, Flávio Juliano; Cordeiro, Gabriela Tavares; Pimenta, Luiz Gustavo Garcia Santos; Viana, Michelle Beatriz; Lopes, Joyce; Gomez, Marcus Vinícius; Aldaz, C. Marcelo; De Marco, Luiz; Gomez, Ricardo Santiago

2014-01-01

296

Oral Medication  

MedlinePLUS

... doctor before starting anything new — even over-the-counter items. Explore: Oral Medication How Much Do Oral Medications Cost? Save money by finding the right type and dosage of medicine for your needs. In this section Treatment and ...

297

LASSBio-881: an N-acylhydrazone transient receptor potential vanilloid subfamily type 1 antagonist orally effective against the hypernociception induced by capsaicin or partial sciatic ligation  

PubMed Central

Background and purpose: Compound LASSBio-881 is an orally effective antinociceptive that binds to cannabinoid receptors and is active mainly on the neurogenic component of pain models. We investigated whether transient receptor potential vanilloid subfamily type 1 (TRPV1) channels are involved in the effects of LASSBio-881. Experimental approach: Modulation of capsaicin (CAP)- and low pH-induced currents was evaluated in TRPV1-expressing Xenopus oocytes. In vivo effects were evaluated in CAP-induced acute and inflammatory changes in nociception, as well as in partial sciatic ligation-induced thermal hypernociception. Key results: LASSBio-881 inhibited TRPV1 currents elicited by CAP with an IC50 of 14 µM, and inhibited proton-gated currents by 70% at 20 µM. Functional interaction with CAP was surmountable. Locally applied LASSBio-881 decreased time spent in CAP-elicited nocifensive behaviour by 30%, and given orally it reduced measures of CAP- or carrageenan-evoked thermal hypernociception by 60 and 40% respectively. In addition, LASSBio-881 decreased the paw withdrawal responses to thermal stimuli of animals with sciatic neuropathy 7–11 days after nerve ligation, at a dose of 300 µmol·kg?1·day?1 p.o. At this dose, hyperthermia was not observed within 4 h following oral administration. Conclusions and implications: LASSBio-881 is a TRPV1 antagonist that apparently competes with CAP. Accordingly, LASSBio-881 inhibited nociception in models of acute, inflammatory and neuropathic pain presumed to involve TRPV1 signalling. These in vivo actions were not hindered by hyperthermia, a common side effect of other TRPV1 antagonists. We propose that the antinociceptive properties of LASSBio-881 are due to TRPV1 antagonism, although other molecular interactions may contribute to the effects of this multi-target drug candidate. PMID:20401963

Tributino, JLM; Santos, MLH; Mesquita, CM; Lima, CKF; Silva, LL; Maia, RC; Duarte, CD; Barreiro, EJ; Fraga, CAM; Castro, NG; Miranda, ALP; Guimaraes, MZP

2010-01-01

298

Chemoprevention of oral cancer: Green tea experience  

PubMed Central

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

299

Salivary RNA Signatures in Oral Cancer Detection  

PubMed Central

Oral squamous cell carcinomas (OSCC) are common malignancies that affect almost a million people every year. The key issue in reducing mortality and morbidity associated with OSCC is to develop novel strategies to identify OSCC at an early stage. One such strategy is the identification of biomarkers. So far, more than 100 biomarkers are recognized in the detection of oral cancer and they range from proteins to nucleic acids (DNAs, RNAs). Detection of ribose nucleic acids in saliva is a recent trend in diagnosing oral cancer. Studies have shown statistically significant changes in the levels of salivary transcriptomes in patients with oral squamous cell carcinomas. These biomarkers have displayed high sensitivity and specificity. Also, new point-of-care platforms such as oral fluid nanosensor test are now available that will soon emerge as chair-side tools for early detection of oral cancer. The aim of this review is to highlight the importance of salivary transcriptomes in oral cancer detection.

Panta, Prashanth; Venna, Venkat Raghavender

2014-01-01

300

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. PMID:24321243

2013-01-01

301

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

2014-08-21

302

Oral and oropharyngeal cancer.  

PubMed

Oral and oropharyngeal cancer (OPC) is a complex and often relentless malignancy prone to local invasion and dissemination. Despite advances in understanding of the disease and improved therapeutic interventions, it continues to be diagnosed at an advanced stage and the survival rate remains poor. The financial cost of treating OPC may be the highest of all cancers in the United States and survivors often experience major detriments to quality of life. Major risk factors for OPC are tobacco, alcohol, areca nut, and human papillomavirus infection. This article updates medical practitioners on the causes, presentation, diagnosis, and management of OPC. PMID:25443678

Huber, Michaell A; Tantiwongkosi, Bundhit

2014-11-01

303

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. PMID:24868161

Schneiderbanger, Daniel; Johannsen, Stephan; Roewer, Norbert; Schuster, Frank

2014-01-01

304

Management of malignant hyperthermia: diagnosis and treatment.  

PubMed

Malignant hyperthermia is a potentially lethal inherited disorder characterized by disturbance of calcium homeostasis in skeletal muscle. Volatile anesthetics and/or the depolarizing muscle relaxant succinylcholine may induce this hypermetabolic muscular syndrome due to uncontrolled sarcoplasmic calcium release via functionally altered calcium release receptors, resulting in hypoxemia, hypercapnia, tachycardia, muscular rigidity, acidosis, hyperkalemia, and hyperthermia in susceptible individuals. Since the clinical presentation of malignant hyperthermia is highly variable, survival of affected patients depends largely on early recognition of the symptoms characteristic of malignant hyperthermia, and immediate action on the part of the attending anesthesiologist. Clinical symptoms of malignant hyperthermia, diagnostic criteria, and current therapeutic guidelines, as well as adequate management of anesthesia in patients susceptible to malignant hyperthermia, are discussed in this review. PMID:24868161

Schneiderbanger, Daniel; Johannsen, Stephan; Roewer, Norbert; Schuster, Frank

2014-01-01

305

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  

Microsoft Academic Search

end of the neutropenic period (>0.5 3 10 9 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

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

2000-01-01

306

Oral Cancer  

MedlinePLUS

Oral Cancer Are You at Risk? What Are the Signs & Symptoms? Should You Have an Oral Cancer Exam? U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES ... Health Early Detection It is important to find oral cancer as early as possible when it can be ...

307

Oral supplementation of Ocimum basilicum has the potential to improves the locomotory, exploratory, anxiolytic behavior and learning in adult male albino mice.  

PubMed

The aim of this project was to determine the effect of 100 mg/ml solvent/kg body weight of Ocimum basilicum leaf extract on neuromuscular co-ordination, exploratory, locomotory and short-term memory formation in male albino mice. Five weeks old, male albino mice were used as the experimental animals in order to demonstrate the effect of O. basilicum's extract on learning and memory. Each male albino mouse was weighted and orally treated either with 100 mg/ml solvent/kg body weight of O. basilicum leaf extract or with commercially available saline solution (Otsuka, Pakistan) for 7 days. Behavioral observations were made by applying a series of neurological tests (Elevated plus maze, Light and dark box, Open field and Rota rod). Dose supplementation continued during neurological testing. It was observed that 100 mg/ml solvent/kg body weight of leaf extract improves neuromuscular co-ordination and male albino mouse performance in open field, light dark box and during novel object test when compared with control group. We concluded that 100 mg/ml solvent/kg body weight of leaf extract has the potential to improve neuromuscular co-ordination, exploratory behavior, object recognition ability and transfer latency in male albino mice and can be safely administrated orally. PMID:25082078

Zahra, K; Khan, M A; Iqbal, F

2015-01-01

308

H(2)S generation and E(h) reduction in cysteine challenge testing as a means of determining the potential of test products and treatments for inhibiting oral malodor.  

PubMed

Bacterial degradation of the sulfur-containing amino acid, cysteine, involves two biochemical processes that contribute significantly to oral malodor generation. The first is production of hydrogen sulfide, a major component and common indicator of oral malodor formation. The second is generation of the sulfhydryl anion, HS(-), an anion that is central to the lowering of the oxidation-reduction potential (E(h)). A reduced E(h) is fundamental to the growth and metabolism of the oral Gram negative anaerobic bacteria. These microorganisms are responsible for oral putrefaction, a process primary to both oral malodor generation and gingivitis-periodontitis development. One purpose of this paper is to report on the testing of a number of anti-malodor treatments and products for their effects on H(2)S formation and E(h) reduction, two processes that occur rapidly and do so simultaneously after the oral bacteria are challenged with cysteine. A second is to report on aspects of cysteine challenge testing in the development of an anti-malodor product composed of ZnCl(2) and sodium chlorite that simultaneously inhibits both H(2)S formation and E(h) reduction and effectively inhibits oral malodor. PMID:21386162

Kleinberg, I; Codipilly, D

2008-03-01

309

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

310

Epigenetic deregulation in myeloid malignancies.  

PubMed

Abnormal epigenetic patterning commonly is observed in cancer, including the myeloid malignancies acute myeloid leukemia and myelodysplastic syndromes. However, despite the universal nature of epigenetic deregulation, specific subtypes of myeloid disorders are associated with distinct epigenetic profiles, which accurately reflect the biologic heterogeneity of these disorders. In addition, mutations and genetic alterations of epigenetic-modifying enzymes frequently have been reported in these myeloid malignancies, emphasizing the importance of epigenetic deregulation in the initiation, progression, and outcome of these disorders. These aberrant epigenetic modifiers have become new targets for drug design, because their inhibition can potentially reverse the altered epigenetic landscapes that contribute to the development of the leukemia. In this review, we provide an overview of the role of epigenetic deregulation in leukemic transformation and their potential for therapeutic targeting. PMID:24813528

Meldi, Kristen M; Figueroa, Maria E

2015-01-01

311

Probiotics and Oral Health  

PubMed Central

The number of products containing probiotics, viable bacteria with proven health benefits, entering the market is increasing. Traditionally, probiotics have been associated with gut health, and most clinical interest has been focused on their use for prevention or treatment of gastrointestinal infections and diseases; however, during the last decade several investigators have also suggested the use of probiotics for oral health purposes. The aim of this review is to examine potential mechanisms of probiotic bacteria in the oral cavity and summarize observed effects of probiotics with respect to oral health. The review focuses on probiotic lactobacilli and bifidobacteria, genera that are most used in various probiotic products. PMID:20613927

Haukioja, Anna

2010-01-01

312

ADHA Oral Health Resources  

NSDL National Science Digital Library

Provided by the American Dental Hygienists' Association, this site's resources are valuable for both dental patients and hygienists to help understand "the importance of oral health to total health." Patients will find informative fact sheets describing potential oral health problems as well as tips for preventing them. Hygienists will find the free posters useful as well as the instructions included for proper brushing and flossing techniques in order to educate and support their patients. The site underscores dental hygienists' roles in tobacco cessation efforts, a major topic of concern in the allied health professions. Providing free "life-saving advice", the ADHA hopes to promote overall heath beginning with oral care.

313

Solitary fibrous tumor of the oral cavity with a predominant leiomyomatous-like pattern: A potential diagnostic pitfall.  

PubMed

The diagnosis of solitary fibrous tumor (SFT) is usually straightforward if the typical morphologic features, including a wide variety of growth patterns, are identified. We report the clinical, radiologic, and pathologic findings of a rare case of intraoral SFT which exhibited a predominant leiomyomatous-like appearance, closely reminiscent of a leiomyoma, at both incisional and excisional biopsy. Histologically, the tumor was composed predominantly of intersecting fascicles of eosinophilic spindle-shaped cells, variably set in a fibrous stroma. A focal hemangiopericytoma-like growth pattern with alternating hypercellular and hypocellular areas, as well as the deposition of dense keloid-type collagen, raising the suspicion of SFT, could be identified only after a careful examination of the whole tumor. Immunohistochemistry was helpful in confirming the diagnosis of SFT, revealing a diffuse staining of neoplastic cells for vimentin, CD34, bcl-2 protein, and, focally, CD99. Myogenic markers (alpha-smooth muscle actin, desmin, h-caldesmon) were not expressed. The pathologist should be aware of this variant of intraoral leiomyomatous-like SFT to avoid a misdiagnosis of leiomyoma. The distinction of SFT from leiomyoma in the oral cavity is important to assure both correct treatment and prognostic information. PMID:20188491

Amico, Paolo; Colella, Giuseppe; Rossiello, Raffaele; Maria Vecchio, Giada; Leocata, Pietro; Magro, Gaetano

2010-07-15

314

Eliglustat tartrate, an orally active glucocerebroside synthase inhibitor for the potential treatment of Gaucher disease and other lysosomal storage diseases.  

PubMed

Eliglustat tartrate (Genz-112638), currently under development by Genzyme Corp, is a glucocerebroside (glucosylceramide) synthase inhibitor for the treatment of Gaucher disease and other lysosomal storage disorders. Gaucher disease is an inherited defect of lysosomal functions caused by mutations in the GBA1 gene leading to accumulation of glucocerebroside, primarily in macrophages. Gaucher disease is characterized by visceromegaly and skeletal complications, including osteoporosis and painful episodes of osteonecrosis. In vitro studies demonstrated that, following exposure to eliglustat tartrate, the abundance of GM1 and GM3 gangliosides in cultured human erythroleukemia cells and murine melanoma cells was decreased. In vivo, eliglustat tartrate administered to Asp409Val/null mice lowered the concentrations of glucocerebroside in the liver, lung and spleen and reduced the number of Gaucher cells in the liver. In a phase Ib clinical trial in healthy volunteers, plasma glucocerebroside concentrations were decreased after dosing with eliglustat tartrate, and in phase II clinical trials in patients with type 1 (non-neuronopathic) Gaucher disease, spleen and liver volumes were diminished. Patients also demonstrated improved bone mineral density, correction of abnormal bone marrow signal with MRI and normalization of glucocerebroside and ganglioside GM3 levels. Eliglustat tartrate is orally active and, with potent effects on the primary identified molecular target for type 1 Gaucher disease and other glycosphingolipidoses, appears likely to fulfill high expectations for clinical efficacy. PMID:20872320

Cox, Timothy M

2010-10-01

315

Phospholipase C gamma 1 is a potential prognostic biomarker for patients with locally advanced and resectable oral squamous cell carcinoma.  

PubMed

The aim of this study was to investigate the prognostic and predictive values of phospholipase C gamma 1 (PLCG1) expression in patients with locally advanced and resectable oral squamous cell carcinoma (OSCC), who were treated in a prospective, randomized, phase 3 trial evaluating standard treatment with surgery and postoperative radiation preceded or not by induction docetaxel, cisplatin, and 5-fluorouracil (TPF). Immunohistochemical staining for PLCG1 was performed on the biopsies of 232 out of 256 OSCC patients at clinical stage III/IVA; the PLCG1 positive score was determined by immunoreactive scoring system. The survival analysis was performed by Kaplan-Meier method; hazard ratios were calculated using the Cox proportional hazards model. Patients with a low PLCG1 expression had a significantly better overall survival (P=0.022), and a trend towards better disease-free survival (P=0.087), loco-regional recurrence-free survival (P=0.058), distant metastasis-free survival (P=0.053), and a high response rate to TPF induction chemotherapy with regard to clinical response (P=0.052) and pathological response (P=0.061), compared to those with high PLCG1 expression. Our results suggest that PLCG1 expression could be used as a prognostic biomarker for patients with advanced OSCC; however, it was not an adequate predictive biomarker for TPF induction chemotherapy. PMID:25085076

Zhu, D; Tan, Y; Yang, X; Qiao, J; Yu, C; Wang, L; Li, J; Zhang, Z; Zhong, L

2014-12-01

316

Spatiotemporal Trends in Oral Cancer Mortality and Potential Risks Associated with Heavy Metal Content in Taiwan Soil  

PubMed Central

Central and Eastern Taiwan have alarmingly high oral cancer (OC) mortality rates, however, the effect of lifestyle factors such as betel chewing cannot fully explain the observed high-risk. Elevated concentrations of heavy metals in the soil reflect somewhat the levels of exposure to the human body, which may promote cancer development in local residents. This study assesses the space-time distribution of OC mortality in Taiwan, and its association with prime factors leading to soil heavy metal content. The current research obtained OC mortality data from the Atlas of Cancer Mortality in Taiwan, 1972–2001, and derived soil heavy metals content data from a nationwide survey carried out by ROCEPA in 1985. The exploratory data analyses showed that OC mortality rates in both genders had high spatial autocorrelation (Moran’s I = 0.6716 and 0.6318 for males and females). Factor analyses revealed three common factors (CFs) representing the major pattern of soil pollution in Taiwan. The results for Spatial Lag Models (SLM) showed that CF1 (Cr, Cu, Ni, and Zn) was most spatially related to male OC mortality which implicates that some metals in CF1 might play as promoters in OC etiology. PMID:21139868

Chiang, Chi-Ting; Lian, Ie-Bin; Su, Che-Chun; Tsai, Kuo-Yang; Lin, Yu-Pin; Chang, Tsun-Kuo

2010-01-01

317

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. PMID:23482881

BOJINCA, Violeta; JANTA, Iustina

2012-01-01

318

Cytoplasmic mediation of malignancy.  

PubMed

The relative roles of nucleus and cytoplasm in the induction and maintenance of the malignant state were studied. Cytoplasmic hybrid (cybrid) clones, derived from the fusion of cytoplasts from malignantly transformed cells to normal whole cells, produced tumors in 17% of the animals injected with them. Nuclear/cytoplasmic hybrid (reconstituted cell) clones, derived by fusion of cytoplasts from malignant cells with karyoplasts of normal cells, produced tumors in 97% of the animals injected. A unique aspect of this study is the fact that all of the cells utilized, both normal and malignantly transformed, were derived from an original cloned cell. PMID:3372452

Israel, B A; Schaeffer, W I

1988-05-01

319

Recurrent malignant glioma in adults.  

PubMed

Meaningful palliation is possible for selected patients with recurrent malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic mixed oligoastrocytoma) using aggressive treatment. Although long-term disease-free survival occurs in fewer than 10% of patients, most who achieve such survival have been treated for multiple recurrences. Surgical resection with the placement of lomustine-releasing wafers is the only therapy proven in randomized trials to be beneficial for recurrent malignant gliomas. Reoperation is indicated when local mass effect limits the quality of life. Reoperation may make other treatments more effective by removing treatment-resistant hypoxic cells and thereby prolonging high-quality survival. Combination chemotherapy (including procarbazine and a nitrosourea) provides dramatic benefit for many recurrent anaplastic or aggressively behaving oligodendrogliomas and anaplastic mixed oligoastrocytomas. For other recurrent malignant gliomas, single-agent cytotoxic chemotherapy (eg, intravenous lomustine or platinums, oral carmustine, temozolomide, or procarbazine) appears to provide equivalent results and better quality of life at a lower cost than do the combinations of cytotoxic drugs. A randomized phase II trial demonstrates that temozolomide provides longer progression-free survival and better quality of life than standard-dose procarbazine in patients with recurrent glioblastoma multiforme. Because benefits of available cytotoxic chemotherapy for anaplastic astrocytoma and glioblastoma are small, participation in clinical trials is appropriate for most patients. Reirradiation (using stereotactic or three-dimensional conformal techniques with or without concomitant cytotoxic chemotherapy) as radiation sensitization can prolong high-quality survival in selected patients. Specific examples include radiosurgery with the gamma knife or with linear accelerators, intracavitary radiation with the newly US Food and Drug Administration-approved GliaSite (Proxima Therapeutics, Alpharetta, GA) radiation therapy system, low dose rate permanent-seed brachytherapy, and high dose rate stereotactic brachytherapy. Dexamethasone (used for the shortest time in the lowest effective doses) can provide symptomatic benefits. Osmotic diuretics such as mannitol reduce cytotoxic edema more rapidly. PMID:12392640

Tatter, Stephen B

2002-12-01

320

Aligning HIV/AIDS Communication With the Oral Tradition of Africans: A Theory-Based Content Analysis of Songs' Potential in Prevention Efforts.  

PubMed

Despite a growing recognition of songs as a useful HIV/AIDS campaign strategy, little research has investigated their potential and/or actual impact. In this study, through a theory-based content analysis, we have assessed the prevention domains covered and the health-relevant constructs promoted by 23 AIDS songs widely used to aid prevention efforts in Ethiopia. To identify the health-relevant constructs and reveal their potential to facilitate or inhibit positive changes, the Extended Parallel Process Model (EPPM) has been used. The findings revealed that the songs cover most of the prevention domains that constitute the current agenda of behavior change communication in Sub-Saharan Africa. However, although all the EPPM variables have been found in almost every song, there were significantly more efficacy messages than threat messages. This suggests that although the songs may lead to positive changes in HIV/AIDS-related outcomes among audiences who have already perceived the threat posed by HIV/AIDS, they are less likely to motivate and thereby generate responses from audiences who have less or no threat perceptions. It is argued that given their potential as a culturally appropriate strategy in Sub-Saharan Africa where oral channels of communication play significant roles, songs could be harnessed for better outcomes through a theory-based design. PMID:24945716

Bekalu, Mesfin Awoke; Eggermont, Steven

2015-05-01

321

Oral premalignant lesions: epidemiological and clinical analysis in the northern Polish population  

PubMed Central

Introduction Leukoplakia is the most common potentially malignant condition of the oral cavity. Aim Epidemiological and clinical analysis of patients with oral leukoplakia (OL) diagnosed and treated in the Department of Maxillofacial and Oral Surgery, Medical University of Gdansk. Material and methods The study was retrospective and prospective. Among 55 911 patients diagnosed and treated in the Department in 1999–2009, 204 people with OL were selected. The material includes 104 women and 100 men with an average age of 58.1. Most of the patients were in the age group of 50–70 years, average age was 58.1. Results The most common concomitant disease was diabetes. More than 88% of the patients declared occurrence of OL predisposing development factors (50.49% – cigarette smoking). Three hundred and twenty foci of OL were found among patients. Homogeneous OL dominated (72.05%). Multifocal OL was diagnosed in 58.3% of patients. The most common location of lesions was buccal mucosa (52.2%). Cancers developed on the basis of OL in 7 patients (3.43%). The percentage of malignant transformation was 12.19% for untreated patients and 1.41% for treated patients. The floor of the oral cavity was proven to be the location of the highest risk of oral squamous cell carcinoma. Patients with diabetes may be more likely to develop OL. The risk of malignant transformation is relatively high. In our material it was equal to 3.43%. Conclusions Cigarette smoking is the most important factor, which can influence the effectiveness of treatment. PMID:25610347

Paw?owska, Anita; Renkielska, Dorota; Michaj?owski, Igor; Sobjanek, Micha?; B?a?ewicz, Izabela

2014-01-01

322

Interleukin-6 in oral diseases: a review.  

PubMed

Interleukin-6 (IL-6) is a pleomorphic cytokine involved in a number of physiologic and pathologic processes including response to trauma and infection and development and progression of inflammation and malignancy. IL-6 is emerging as an important mediator and novel therapeutic target for chronic inflammatory diseases and cancer. The present study reviews the available evidence regarding the association between IL-6 and a range of oral diseases including infections (periodontal disease and endodontic infections), immunologically mediated disorders (oral lichen planus and Sjögren's syndrome) and malignancy (oral cancer and precancer). The role of common genetic variants of IL-6 in determining individual susceptibility to certain oral diseases, as well as novel therapeutic strategies based on IL-6 inhibition are also discussed. PMID:22050374

Nibali, L; Fedele, S; D'Aiuto, F; Donos, N

2012-04-01

323

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. PMID:22719913

Zhang, Chen-Yang; Zhang, Xiao-Yun; Shi, Lin-Jun; Zhou, Zeng-Tong; Jiang, Wei-Wen

2012-01-01

324

‘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

325

The modulatory effect of cell–cell contact on the tumourigenic potential of pre-malignant epithelial cells: a computational exploration  

PubMed Central

Malignant development cannot be attributed alone to genetic changes in a single cell, but occurs as a result of the complex interplay between the failure of cellular regulation mechanisms and the presence of a permissive microenvironment. Although E-cadherin is classified as a ‘metastasis suppressor’ owing to its role in intercellular adhesion, the observation that it may be downregulated at a premalignant stage is indicative of additional roles in neoplastic development. We have used an agent-based computational model to explore the emergent behaviour resulting from the interaction of single and subpopulations of E-cadherin-compromised cells with unaffected normal epithelial cells within a monolayer environment. We have extended this to investigate the importance of local tissue perturbations in the form of scratch-wounding, or ablation of randomly-dispersed normal cells, on the growth of a single cell exhibiting E-cadherin loss. Our results suggest that the microenvironment with respect to localized cell density and normal/E-cadherin-compromised neighbours is crucial in determining whether an abnormal individual cell proliferates or remains dormant within the monolayer. These predictions raise important questions relating to the propensity for individual mutations to give rise to disease, and future experimental exploration of these will enhance our understanding of a complex, multifactorial pathological process. PMID:23097504

Walker, D. C.; Southgate, J.

2013-01-01

326

A new mutation in the skeletal ryanodine receptor gene (RYR1) is potentially causative of malignant hyperthermia, central core disease, and severe skeletal malformation.  

PubMed

Malignant hyperthermia susceptibility (MHS) and central core disease (CCD) have been shown to result from missense mutations in the ryanodine receptor gene of the skeletal muscle (RYR1). A 15-year-old patient who had spondylocostal dysostosis (SCD) developed an MH crisis during general anesthesia. The patient was characterized phenotypically by block vertebrae, vertebral fusion, short neck and thorax, fused ribs, craniofacial abnormalities, spina bifida occulta, and a diaphragmatic defect closed surgically in early infancy. The diagnosis MH susceptible (MHS) was confirmed by the in vitro contracture test (IVCT) on a muscle biopsy. Surprisingly, the histopathological investigation revealed the presence of CCD too. Molecular genetic investigation of the RYR1 gene was performed to search for known MH-related mutations. Cluster regions of the RYR1 gene, in which mutations have already been found, were examined by direct automated sequencing. In addition to the diagnosis MHS and CCD we were able to identify a novel RYR1 mutation in exon 46: 7358ATC > ACC, resulting in an Ile2453Thr substitution. This mutation was also present in the mother, in whom MH disposition and CCD were determined by muscle investigations. We suggest that the newly identified RYR1 mutation is closely associated with MH and CCD. A probable causative role of the RYR1 gene in SCD patients should be assessed by further genetic investigations. PMID:14708096

Rueffert, Henrik; Olthoff, Derk; Deutrich, Christine; Schober, Ralf; Froster, Ursula G

2004-01-30

327

The Evaluation of Hydroxyethyl Starch (6% HES 130/0.4) Solution's Potential Preventive Effects on Coagulation Status in Women with Gynecologic Malignancies Using Rotation Thromboelastography.  

PubMed

Objective: The aim of this study was to determine the effects of in vitro hemodilution with 6% hydroxyethyl starch (HES) 130/0.4 solution on the coagulation status of women with gynecologic malignancies by using rotation thromboelastogram (ROTEM®). Materials and Methods: Twenty-two patients with gynecological tumors scheduled for anesthesia were enrolled. Blood samples were diluted by 20% with 6% HES (130/0.4) solution. Results: In the INTEM assay, clotting time (CT) (p<0.01) and clot formation time (CFT) (p<0.001) were significantly increased and maximum maximum clot formation (MCF) (p<0.001) was significantly decreased in HES hemodilution compared with the undiluted control samples. In the EXTEM assay, there was a similar significant increase in increase in CFT (p<0.01) and a decrease in maximum a decrease in MCF (p<0.01) in HES hemodilution when compared with control samples. Conclusion: HES 130/0.4 solution causes significant hypocoagulable changes in the thromboelastographic profile of gynecologic cancer patients in vitro. PMID:25330518

Akay, Meltem Olga; Bilir, Ayten; Oge, Tufan; Ku?, Gökhan; Mutlu, Fezan Sahin

2014-09-01

328

The Evaluation of Hydroxyethyl Starch (6% HES 130/0.4) Solution’s Potential Preventive Effects on Coagulation Status in Women with Gynecologic Malignancies Using Rotation Thromboelastography  

PubMed Central

Objective: The aim of this study was to determine the effects of in vitro hemodilution with 6% hydroxyethyl starch (HES) 130/0.4 solution on the coagulation status of women with gynecologic malignancies by using rotation thromboelastogram (ROTEM®). Materials and Methods: Twenty-two patients with gynecological tumors scheduled for anesthesia were enrolled. Blood samples were diluted by 20% with 6% HES (130/0.4) solution. Results: In the INTEM assay, clotting time (CT) (p<0.01) and clot formation time (CFT) (p<0.001) were significantly increased and maximum maximum clot formation (MCF) (p< 0.001) was significantly decreased in HES hemodilution compared with the undiluted control samples. In the EXTEM assay, there was a similar significant increase in increase in CFT (p<0.01) and a decrease in maximum a decrease in MCF (p<0.01) in HES hemodilution when compared with control samples. Conclusion: HES 130/0.4 solution causes significant hypocoagulable changes in the thromboelastographic profile of gynecologic cancer patients in vitro. PMID:25330518

Akay, Meltem Olga; Bilir, Ayten; Öge, Tufan; Ku?, Gökhan; Mutlu, Fezan ?ahin

2014-01-01

329

Oxygenated hemoglobin diffuse reflectance ratio for in vivo detection of oral pre-cancer.  

PubMed

Diffuse reflectance (DR) spectroscopy is a simple, low-cost, and noninvasive modality with potential for distinguishing oral precancer. Recently, in an ex vivo study, the DR spectral ratio (R545/R575) of oxygenated hemoglobin bands at 545 and 575 nm was used for grading malignancy. This work presents the results of clinical trials conducted in 29 patients to detect oral precancer using this ratio. We use site-specific normal spectra from a group of 36 healthy volunteers for comparison with those of patients. Toward this, in vivo DR spectra from 14 anatomical sites of the oral cavity of healthy volunteers are recorded on a miniature fiber optic spectrometer with white light excitation. The R545/R575 ratio is lowest for healthy tissues and appears to increase with the grade of malignancy. As compared to scatter plots that use the mean DR ratio from all anatomical sites, those using site-specific data show improved sensitivity and specificity for early diagnosis and grading of oral cancer. In the case of buccal mucosa, using scatter plots of R545/R575 ratio, we obtain a sensitivity of 100% and specificity of 86% for discriminating precancer (dysplasia) from hyperplasia, and a sensitivity of 97% and specificity of 86% for discriminating hyperplasia from normal. PMID:19021314

Mallia, Rupananda; Thomas, Shiny Sara; Mathews, Anitha; Kumar, Rejnish; Sebastian, Paul; Madhavan, Jayaprakash; Subhash, Narayanan

2008-01-01

330

Better grade of tumor differentiation of oral squamous cell carcinoma arising in background of oral submucous fibrosis.  

PubMed

Oral submucous fibrosis (OSMF) is a potentially malignant disorder of the oral cavity. Most of the people affected by OSMF are betel quid chewers. It is characterized by epithelial atrophy and progressive accumulation of collagen fibers in lamina propria and submucosa of the oral mucosa. 7.6% of OSMF cases undergo oral squamous cell carcinoma (OSCC) transformation of which majority display low grade of tumor differentiation. In the present paper, a hypothesis has been proposed to correlate atrophy, turnover rate and surface keratization in OSMF with degree of tumor differentiation in OSCC. A novel hypothesis for epithelial atrophy in OSMF has also been emphasized. High proliferative activity and basal cell hyperplasia in conjunction with rapid exfoliation of superficial cells and epithelial atrophy suggest that epithelial turnover rate is very high in OSMF. Presence of surface keratinized layer in this situation suggests faster maturation or differentiation of epithelium in OSMF. Thus, the epithelial cells are genetically programmed for high turnover rate and faster differentiation or maturation to form keratin. During malignant transformation of OSMF, the transformed epithelial cells may retain the genetic memory of faster differentiation and maturation resulting in better grade of tumor differentiation. The well differentiated OSCC has good prognosis, better survival rate and less chances of recurrence of regional and distant metastasis. Studies are needed to explore the biomarkers or molecular markers associated with carcinogenesis like genetic instability, oncogenes, tumor suppressor genes and angiogenesis in OSCC associated with OSMF. If investigated in the suggested direction, it might provide some important clues about the pathogenesis of OSCC arising in background of OSMF and for the future development of treatment strategies. PMID:23891040

Sarode, Sachin C; Sarode, Gargi S

2013-10-01

331

American Oral Literature: Our Forgotten Heritage  

ERIC Educational Resources Information Center

Focuses on American Indian and Afro-American oral tradition to explore the substance and potential pedagogic value of American oral literature. Stresses the literary value of modern folk literature, including popular songs and rhetoric. (Author/JB)

Haslam, Gerald

1971-01-01

332

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

333

General Information about Malignant Mesothelioma  

MedlinePLUS

... form in the lining of the chest or abdomen. Malignant mesothelioma is a disease in which malignant ( ... that examine the inside of the chest and abdomen are used to detect (find) and diagnose malignant ...

334

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. PMID:22529584

Beena, VT; Panda, Swagatika; Heera, R; Rajeev, R

2011-01-01

335

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. PMID:25024837

Shirzad, Atena; Pouramir, Mahdi; Seyedmajidi, Maryam; Jenabian, Niloofar; Bijani, Ali; Motallebnejad, Mina

2014-01-01

336

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

PubMed

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

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

2011-01-01

337

Distinct clinicopathological features of NAB2-STAT6 fusion gene variants in solitary fibrous tumor with emphasis on the acquisition of highly malignant potential.  

PubMed

The impact of NGFI-A binding protein 2 (NAB2)-signal transducer and activator of transcription 6 (STAT6) fusion on the biological behavior and the mechanism of acquisition of malignant phenotype in solitary fibrous tumor (SFT) is not well understood. We examined variations of the NAB2-STAT6 fusion gene in 40 cases of SFT using formalin-fixed, paraffin-embedded tissues and secondary genetic alterations of tumor protein p53 (TP53),, platelet-derived growth factor receptor, ? polypeptide (PDGFRB), and telomerase reverse transcriptase (TERT) promoters. These gene variations were compared with the clinicopathological features. The 2-year and 5-year disease-free survival rates (DFSRs) were 91% and 83%, respectively. All 40 samples demonstrated nuclear staining for STAT6, including CD34-negative cases. Moreover, p53-positive staining was associated with a lower DFSR and was significantly associated with higher Ki-67 label index, higher mitotic rate (mitosis, >4/high-power field), and the presence of nuclear atypia/pleomorphism. NAB2-STAT6 fusions were detected in all of the cases; the NAB2 exon 4-STAT6 exon 2, the most common genotype, appeared in 18 cases, which was associated with thoracic tumor location and the less aggressive phenotype. In contrast, tumors with NAB2 exon 6-STAT6 exon 16/18 demonstrated an aggressive phenotype. Mutations in TP53 and PDGFRB were detected in 2 and 3 cases respectively, and these occurred in a mutually exclusive fashion. TERT promoter hot spot mutations were observed in 5 cases, which were associated with shorter DFSR. Two dedifferentiated SFT cases harbored both TP53 and TERT promoter mutations. TP53 mutations, which result in its overexpression, in combination with TERT promoter mutations seem to play an important role in the dedifferentiation process. PMID:25582503

Akaike, Keisuke; Kurisaki-Arakawa, Aiko; Hara, Kieko; Suehara, Yoshiyuki; Takagi, Tatsuya; Mitani, Keiko; Kaneko, Kazuo; Yao, Takashi; Saito, Tsuyoshi

2015-03-01

338

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. 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

2014-01-01

339

Development of 2-aminooxazoline 3-azaxanthenes as orally efficacious ?-secretase inhibitors for the potential treatment of Alzheimer's disease.  

PubMed

The ?-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is one of the most hotly pursued targets for the treatment of Alzheimer's disease. We used a structure- and property-based drug design approach to identify 2-aminooxazoline 3-azaxanthenes as potent BACE1 inhibitors which significantly reduced CSF and brain A? levels in a rat pharmacodynamic model. Compared to the initial lead 2, compound 28 exhibited reduced potential for QTc prolongation in a non-human primate cardiovascular safety model. PMID:25613679

Chen, Jian Jeffrey; Liu, Qingyian; Yuan, Chester; Gore, Vijay; Lopez, Patricia; Ma, Vu; Amegadzie, Albert; Qian, Wenyuan; Judd, Ted C; Minatti, Ana E; Brown, James; Cheng, Yuan; Xue, May; Zhong, Wenge; Dineen, Thomas A; Epstein, Oleg; Human, Jason; Kreiman, Charles; Marx, Isaac; Weiss, Matthew M; Hitchcock, Stephen A; Powers, Timothy S; Chen, Kui; Wen, Paul H; Whittington, Douglas A; Cheng, Alan C; Bartberger, Michael D; Hickman, Dean; Werner, Jonathan A; Vargas, Hugo M; Everds, Nancy E; Vonderfecht, Steven L; Dunn, Robert T; Wood, Stephen; Fremeau, Robert T; White, Ryan D; Patel, Vinod F

2015-02-15

340

Oral implants.  

PubMed

Today, more and more evidence suggests that even small changes in hardware for oral implants may jeopardize its biocompatibility. Even the manner in which the hardware is sterilized can influence cellular adhesion. This review discusses the surface characteristics, configuration, and success rates of various oral implants, as well as the complications that can result following implantation. PMID:1777657

van Steenberghe, D

1991-04-01

341

Bacillus subtilis spores expressing the VP28 antigen: a potential oral treatment to protect Litopenaeus vannamei against white spot syndrome.  

PubMed

The envelope protein VP28 of white spot syndrome virus (WSSV) is considered a candidate antigen for use in a potential vaccine to this important shrimp pathogen (the cause of white spot syndrome, WSS). Here, we used spores of Bacillus subtilis to display VP28 on the spore surface. Trials were conducted to evaluate their ability to protect shrimps against WSSV infection. The gene cotB-vp28 was integrated into the chromosome of the laboratory strain B. subtilis PY79, and expression of CotB-VP28 was detected by Western blotting and immunofluorescence. Expression of CotB-VP28 was equivalent to 1000 molecules per spore. PY79 and CotB-VP28 spores were mixed with pellets for feeding of whiteleg shrimps (Litopenaeus vannamei), followed by WSSV challenge. Superoxidase dismutase (SOD), phenoloxidase activities and mortality rates of the two shrimp groups were evaluated. Groups fed with PY79 and CotB-VP28 spores at day 7 had increased SOD activities of 29% and increased phenoloxidase activities of 15% and 33%, respectively, compared to those of the control group. Fourteen days postchallenge, 35% of vaccinated shrimps had died compared to 49% of those fed naked spores (PY79) and 66% untreated, unchallenged animals. These data suggest that spores expressing VP28 have potential as a prophylactic treatment of WSS. PMID:25066511

Nguyen, Anh T V; Pham, Cuong K; Pham, Huong T T; Pham, Hang L; Nguyen, Anh H; Dang, Lua T; Huynh, Hong A; Cutting, Simon M; Phan, Tuan-Nghia

2014-09-01

342

Treatment Option Overview (Malignant Mesothelioma)  

MedlinePLUS

... are different types of treatment for patients with malignant mesothelioma. Different types of treatments are available for patients with malignant mesothelioma . Some treatments are standard (the currently used ...

343

[Prognostic and predictive markers of malignant melanoma].  

PubMed

Malignant melanoma biologically can be divided into non-metastatic and metastatic forms which cannot be predicted precisely using classical clinicopathological parameters, therefore studies on novel genetic or protein markers are abundant in the literature. These studies did not result in clinically useful markers because mostly ignored the results of studies on the genetic basis of metastatic potential of malignant melanoma. Accordingly, the list of promising novel markers is short (BCL2, CDK2, MART-1, OPN). Similar to other solid malignancies, introduction of targeted therapy into clinical practice of melanoma turned the attention toward the genetic basis of resistance to chemo- and targeted therapies. These novel data could lead to the development of molecular diagnostics which can help in designing more effective therapeutic strategies of malignant melanoma. PMID:23795352

Rásó, Erzsébet; Barbai, Tamás; Győrffy, Balázs; Tímár, József

2013-06-01

344

[Extended cycle oral contraceptives].  

PubMed

Oral contraceptive pills are conventionally prescribed in a manner that causes monthly withdrawal uterine bleeding (lunar month). The reasons for this are historical without an inherent medical need. According to our literature search, there are patients' demands for less frequent menstrual cycles. We have learned from patients who were given the pill continuously for long periods due to medical or social indications that continuous administration of the contraceptive pill is feasible and safe. In the current review, the authors have searched the literature regarding extended cycle oral contraception for periods of time up to one year. This way of administration of the pill is not compromising the efficacy of pregnancy prevention, nor is it detrimental in terms of cardiovascular and hemostatic complications or endometrial malignancy. It is known that there is a slightly increased risk of breast cancer in users of oral contraceptives up to 10 years, regardless of the mode of administration. From a few studies of hormone replacement therapy in postmenopausal women, there is concern that continuous treatment may be deleterious, while sequential is not. Extended cycle contraceptive treatment has a few side effects, mainly increased breakthrough bleeding but decreased withdrawal bleeding. Other side effects were less prevalent than in conventional administration. PMID:17990394

Geist, Ruth; Beyth, Yoram

2007-10-01

345

[Chemotherapy for malignant gliomas: an update].  

PubMed

Gliomas account for approximately 30% of all brain tumors and are thus the most common primary tumors of the central nervous system (CNS). Despite treatment with aggressive surgical resection, chemotherapy, and radiotherapy, high-grade (WHO grades III and IV) malignant gliomas, especially glioblastoma (GBM), the most common glioma in adults, kill patients within a median time span of a year after diagnosis. In Japan, alkylating agents such as 1-(4-amino-2-methyl-5-pyridiminyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) and methyl-6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) have been used to treat malignant gliomas for a long time; however, this treatment provides few clinical benefits. Temozolomide (TMZ), an oral alkylating agent, has been demonstrated to possess antitumor activity against malignant gliomas with minimal additional toxicity; furthermore, a previous study found that treatment with TMZ significantly prolonged median survival time. In 2006, TMZ was certified as the treatment agent for malignant gliomas by the National Ministry of Health and Welfare of Japan. It is now used as first-line therapy. However, its clinical outcomes depend on the O6-methylguanine-DNA methyltransferase (MGMT) status, and MGMT modification is one of the key factors to deriving greater clinical benefits in the future. Combination therapy with TMZ and other antitumor drugs, especially anti-vascular endothelial growth factor (VEGF) antibody (Avascin), has been aggressively investigated for treating gliomas. Some of these drugs have been studied in experimental animal models and advanced to clinical trials. These studies suggest that combination therapy with TMZ and other antitumor drugs might further improve the clinical outcome of malignant gliomas as compared to TMZ plus radiotherapy. Based on these data, the next step will be to carry out phase II to III clinical studies to improve treatment of malignant brain tumors further. PMID:24105052

Wakabayashi, Toshihiko; Natsume, Atsushi; Fujii, Masazumi

2013-10-01

346

Pro-Arrhythmic Potential of Oral Antihistamines (H1): Combining Adverse Event Reports with Drug Utilization Data across Europe  

PubMed Central

Background There is appreciable utilisation of antihistamines (H1) in European countries, either prescribed by physician and purchased by patients for self-medication. Terfenadine and astemizole underwent regulatory restrictions in ’90 because of their cardiac toxicity, but only scarce clinical data are available on other antihistamines. Aim To investigate the pro-arrhythmic potential of antihistamines by combining safety reports of the FDA Adverse Event Reporting System (FAERS) with drug utilization data from 13 European Countries. Methods We identified signals of antihistamine arrhythmogenic potential by analyzing FAERS database for all cases of Torsades de Pointes (TdP), QT abnormalities (QTabn), ventricular arrhythmia (VA) and sudden cardiac death/cardiac arrest (SCD/CA). Number of cases ?3 and disproportionality were used to define alert signals: TdP and QTabn identified stronger signals, whereas SCD/CA identified weaker signals. Drug utilization data from 2005 to 2010 were collected from administrative databases through health authorities and insurance. Results Antihistamines were reported in 109 cases of TdP/QT prolongation, 278 VA and 610 SCD/CA. Five agents resulted in stronger signals (cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine) and 6 in weaker signals (alimemazine, carbinoxamine, cyclizine, cyproeptadine, dexchlorpheniramine and doxylamine). Exposure to antihistamines with stronger signal was markedly different across European countries and was at least 40% in each Country. Cetirizine was >29 Defined Daily Doses per 1000 inhabitants per day (DID) in Norway, desloratadine >11 DID in France and loratadine >9 DID in Sweden and Croatia. Drugs with weaker signals accounted for no more than 10% (in Sweden) and in most European countries their use was negligible. Conclusions Some second-generation antihistamines are associated with signal of torsadogenicity and largely used in most European countries. Although confirmation by analytical studies is required, regulators and clinicians should consider risk-minimisation activities. Also antihistamines without signal but with peculiar use in a few Countries (e.g., levocetirizine) or with increasing consumption (e.g., rupatadine) deserve careful surveillance. PMID:25785934

Poluzzi, Elisabetta; Raschi, Emanuel; Godman, Brian; Koci, Ariola; Moretti, Ugo; Kalaba, Marija; Wettermark, Bjorn; Sturkenboom, Miriam; De Ponti, Fabrizio

2015-01-01

347

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. PMID:20155361

Genden, Eric M.; Silver, Carl E.; Takes, Robert P.; Suárez, Carlos; Owen, Randall P.; Haigentz, Missak; Stoeckli, Sandro J.; Shaha, Ashok R.; Rapidis, Alexander D.; Rodrigo, Juan Pablo; Rinaldo, Alessandra

2010-01-01

348

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. PMID:24959038

Pinisetti, Soujanya; Manyam, Ravikanth; Suresh, Babburi; Aparna, V

2014-01-01

349

Malignant degeneration in burn scars.  

PubMed

The malignant potential of burn scars has been recognized since Marjolin's classical description of cancer arising in several types of post-traumatic scars. With improved burn therapy since the last war, there has been a higher survival rate of severe burns with proportionate increase in cancer associated with burn scars. This will create increasing problems of permanent disability and compensation. The younger the patient at the time of the burn, the longer the time required for the cancer to develop. Acute cancer development in burn scars has been reported after a four-week interval. Cancer may develop from six weeks to fifty years or more. The etiology of cancer in burn scars is not known. The most important clinical finding is the fact that most of the burn cancers occur in areas which were not grafted. The most common type of cancer encountered in burn scars is squamous cell carcinoma, which forms in Marjolin ulcers. Basal cell carcinoma may develop in the most superficial of burn scars.Treatment should be directed primarily to prompt and adequate skin grafting in all deep burns in order to prevent malignant degeneration of the burn scars. Once it has developed the treatment is the same as for other malignancies which are not associated with burns. Wide surgical excision with block dissection of the regional lymph nodes when they are involved is the treatment of choice. The prognosis of burn scar cancer is poor, once the process has extended because of early and distant metastasis. PMID:13691372

CASTANARES, S

1961-03-01

350

Melatonin and Oral Cavity  

PubMed Central

While initially the oral cavity was considered to be mainly a source of various bacteria, their toxins and antigens, recent studies showed that it may also be a location of oxidative stress and periodontal inflammation. Accordingly, this paper focuses on the involvement of melatonin in oxidative stress diseases of oral cavity as well as on potential therapeutic implications of melatonin in dental disorders. Melatonin has immunomodulatory and antioxidant activities, stimulates the proliferation of collagen and osseous tissue, and acts as a protector against cellular degeneration associated with aging and toxin exposure. Arising out of its antioxidant actions, melatonin protects against inflammatory processes and cellular damage caused by the toxic derivates of oxygen. As a result of these actions, melatonin may be useful as a coadjuvant in the treatment of certain conditions of the oral cavity. However, the most important effect of melatonin seems to result from its potent antioxidant, immunomodulatory, protective, and anticancer properties. Thus, melatonin could be used therapeutically for instance, locally, in the oral cavity damage of mechanical, bacterial, fungal, or viral origin, in postsurgical wounds caused by tooth extractions and other oral surgeries. Additionally, it can help bone formation in various autoimmunological disorders such as Sjorgen syndrome, in periodontal diseases, in toxic effects of dental materials, in dental implants, and in oral cancers. PMID:22792106

Cengiz, Murat ?nanç; Cengiz, Seda; Wang, Hom-Lay

2012-01-01

351

Thoracic Malignancy Steering Committee  

Cancer.gov

The Thoracic Malignancy Steering Committee evaluates and prioritizes concepts for phase 3 and large phase 2 therapeutic clinical trials to be conducted in the NCI National Clinical Trials Network (NCTN).

352

Brain Malignancies Steering Committee  

Cancer.gov

The Brain Malignancy Steering Committee evaluates and prioritizes concepts for phase 3 and large phase 2 therapeutic clinical trials to be conducted in the NCI National Clinical Trials Network (NCTN).

353

[Malignant pheochromocytoma. A case].  

PubMed

A case of malignant phaeochromocytoma is reported. The primary tumour was removed in 1970. Metastases were diagnosed in 1979 and management of the condition included antihypertensive treatment with alphamethylparatyrosine, antitumoral chemotherapy and surgical reduction of secreting tissue. In these rare tumours malignancy can only be confirmed by metastases, i.e. presence of chromaffin cells in loci where they are not usually found. Histology is of little value. High levels of catecholamine precursors or their metabolites in the urine may be a sign of malignancy, but some asymptomatic tumours are only revealed by metastases. Computerized tomography and radioisotope scanning with I131 metaiodobenzylguanidine are the best available methods to locate the lesions. In view of the small number of cases and of the unpredictable course (sometimes spread over many years) of malignant phaeochromocytomas, the effectiveness of treatments with alphamethylparatyrosine, chemotherapy and radiotherapy is difficult to evaluate. PMID:3156338

Ducornet, B; Bacourt, F; Gensous, D; Jacquillat, C; Duprey, J; Tcherdakoff, P

1985-01-26

354

Gynecologic malignancy in pregnancy  

PubMed Central

Gynecologic malignancy during pregnancy is a stressful problem. For the diagnosis and treatment of malignancy during pregnancy, a multidisciplinary approach is needed. Patients should be advised about the benefits and risk of treatment. When selecting a treatment for malignancy during pregnancy, the physiologic changes that occur with the pregnancy should be considered. Various diagnostic procedures that do not harm the fetus can be used. Laparoscopic surgery or laparotomy may be safely performed. The staging approach and treatment should be standard. Systemic chemotherapy during the first trimester should be delayed if possible. Radiation therapy should preferably start postpartum. Although delivery should be delayed preferably until after 35 weeks of gestation, termination of pregnancy may be considered when immediate treatment is required. Subsequent pregnancies do not increase the risk of malignancy recurrence. PMID:24328018

Ji, Yong Il

2013-01-01

355

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

356

Thoracic Malignancy Steering Committee  

Cancer.gov

The TMSC functions to harmonize an efficient, cost-effective, science-driven, and transparent process that will identify and promote the "Best Science" in clinical research of lung and other thoracic malignancies by addressing the design and prioritization of phase III trials and large phase II studies in chest malignancies. In addition to focusing on lung cancer, the TMSC addresses oncology trials in other thoracic sites, such as mesothelioma. Esophageal cancer trials are reviewed by the Gastrointestinal Cancer Steering Committee.

357

[Malignant nail tumors].  

PubMed

Because of the large number of different tissues making up the distal phalanx of fingers and toes, a large variety of malignant tumors can be found in and around the nail apparatus. Bowen disease is probably the most frequent nail malignancy. It is usually seen as a verrucous plaque of the nail fold and nail bed in persons above the age of 40 years. It slowly grows over a period of years or even decades before degenerating to an invasive squamous cell carcinoma. The latter may also occur primarily often as a weeping onycholysis. The next most frequent nail malignancy is ungual melanoma. Those arising from the matrix are usually pigmented and often start with a longitudinal melanonychia whereas those originating from the nail bed remain amelanotic, are often nodular and mistaken for an ingrown nail in an elderly person. The treatment of choice for in situ and early invasive subungual melanomas is generous extirpation of the nail apparatus whereas distal amputation is only indicated for advanced melanomas. In addition to these frequent nail malignancies, nail-specific carcinomas, malignant vascular and osseous tumors, other sarcomas, nail involvement in malignant systemic disorders and metastases may occur. In most cases, they cannot be diagnosed accurately on clinical grounds. Therefore, a high degree of suspicion is necessary in all isolated or single-digit proliferations that do not respond to conservative treatment. PMID:24718507

Haneke, E

2014-04-01

358

Potential clinical application of masseter and temporal muscle massage treatment using an oral rehabilitation robot in temporomandibular disorder patients with myofascial pain.  

PubMed

Objectives: To investigate the safety, suitable treatment regimen, and efficacy of masseter and temporal muscle massage treatment using an oral rehabilitation robot. Methods: Forty-one temporomandibular disorder (TMD) patients with myofascial pain (8 men, 33 women, median age: 46 years) were enrolled. The safety, suitable massage regimen, and efficacy of this treatment were investigated. Changes in masseter muscle thickness were evaluated on sonograms. Results: No adverse events occurred with any of the treatment sessions. Suitable massage was at pressure of 10 N for 16 minutes. Five sessions were performed every 2 weeks. Total duration of treatment was 9·5 weeks in median. Massage treatment was effective in 70·3% of patients. Masseter muscle thickness decreased with treatment in the therapy-effective group. Conclusion: This study confirmed the safety of massage treatment, and established a suitable regimen. Massage was effective in 70·3% of patients and appeared to have a potential as one of the effective treatments for myofascial pain. PMID:25384890

Ariji, Yoshiko; Nakayama, Miwa; Nishiyama, Wataru; Ogi, Nobumi; Sakuma, Shigemitsu; Katsumata, Akitoshi; Kurita, Kenichi; Ariji, Eiichiro

2014-11-11

359

Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential  

SciTech Connect

Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na3 [ae-B20H17NH3], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 {+-} 16.1 ppm at 48 h and to 43.9 {+-} 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.

David W. Nigg

2012-05-01

360

Oral Appliances  

MedlinePLUS

... two categories. The diverse variety is simply a variation of a few major themes. Oral appliances can be classified by mode of action or design variation. Tongue Retaining Appliances Tongue retaining appliances hold the ...

361

Oral graft-versus-host disease.  

PubMed

Hematopoietic cell transplantation is used to treat malignancies, hematologic and immune deficiency states, marrow failure syndromes, and autoimmune diseases. Graft-versus-host disease (GVHD) is a clinical syndrome seen following allogeneic transplantation where donorderived immunocompetent T cells and inflammatory responses attack host tissues. GVHD can cause significant morbidity and even result in mortality. The oral cavity is a frequently involved site with clinical changes resembling autoimmune collagen vascular diseases. Recognition, diagnosis, and monitoring of oral GVHD can help with diagnosis and grading of GVHD and judging responses to therapy. Topical and local management of symptomatic oral GVHD can reduce oral symptoms that can interfere with oral function and quality of life, and can reduce the need for more intensive immunosuppressive systemic therapies. PMID:18154866

Schubert, Mark M; Correa, Maria Elvira Pizzigatti

2008-01-01

362

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 probes and highlight the role of optical imaging such as autofluorescence, fluorescence diagnosis (FD), laser confocal endomicroscopy (LCE), surface enhanced Raman spectroscopy (SERS), optical coherence tomography (OCT) and confocal reflectance microscopy (CRM) in early oral cancer detection. FD is a promising method to differentiate cancerous lesions from benign, thus helping in the determination of adequate resolution of surgical resection margin. LCE offers in vivo cellular imaging of tissue structures from surface to subsurface layers and has demonstrated the potential to be used as a minimally invasive optical biopsy technique for early diagnosis of oral cancer lesions. SERS was able to differentiate between normal and oral cancer patients based on the spectra acquired from saliva of patients. OCT has been used to visualize the detailed histological features of the oral lesions with an imaging depth down to 2–3 mm. CRM is an optical tool to noninvasively image tissue with near histological resolution. These comprehensive diagnostic modalities can also be used to define surgical margin and to provide a direct assessment of the therapeutic effectiveness. PMID:24310585

Olivo, Malini; Bhuvaneswari, Ramaswamy; Keogh, Ivan

2011-01-01

363

Primary Malignant Rhabdoid Melanoma  

PubMed Central

Melanoma with rhabdoid features is an uncommon variant of malignant melanoma. Here, we describe a rare case of primary rhabdoid malignant melanoma. A 54-year-old man presented with a black tumor measuring 3×4 cm on the right forearm. Histologic sections showed a tumor mass with rhabdoid features composed entirely of polygonal neoplastic cells with eccentric nuclei, prominent nucleoli, and large hyaline cytoplasmic inclusions. The tumor cells were immunoreactive with HMB-45, S100, Fontana-Masson silver and vimentin, and negative for smooth muscle actin, CD68, CD34, CD99, synaptophysin, desmin, and PAS. The differential diagnosis for this tumor included malignant peripheral nerve sheath tumor, malignant peripheral neuroectodermal tumor and rhabdomyosarcoma. The patient was treated with a wide excision and a local skin graft. The excised tumor was entirely composed of rhabdoid tumor cells. No recurrence or metastasis was evident 4 months after removal. This article is relevant to rare cases of primary malignant melanomas showing rhabdoid tumor cells over the entire excised lesion. PMID:22148039

Chung, Bo Young; Ahn, In Su; Cho, Soo Ick; Kim, Hye One; Kim, Kwang Ho; Park, Chun Wook

2011-01-01

364

Primary malignant rhabdoid melanoma.  

PubMed

Melanoma with rhabdoid features is an uncommon variant of malignant melanoma. Here, we describe a rare case of primary rhabdoid malignant melanoma. A 54-year-old man presented with a black tumor measuring 3×4 cm on the right forearm. Histologic sections showed a tumor mass with rhabdoid features composed entirely of polygonal neoplastic cells with eccentric nuclei, prominent nucleoli, and large hyaline cytoplasmic inclusions. The tumor cells were immunoreactive with HMB-45, S100, Fontana-Masson silver and vimentin, and negative for smooth muscle actin, CD68, CD34, CD99, synaptophysin, desmin, and PAS. The differential diagnosis for this tumor included malignant peripheral nerve sheath tumor, malignant peripheral neuroectodermal tumor and rhabdomyosarcoma. The patient was treated with a wide excision and a local skin graft. The excised tumor was entirely composed of rhabdoid tumor cells. No recurrence or metastasis was evident 4 months after removal. This article is relevant to rare cases of primary malignant melanomas showing rhabdoid tumor cells over the entire excised lesion. PMID:22148039

Chung, Bo Young; Ahn, In Su; Cho, Soo Ick; Kim, Hye One; Kim, Kwang Ho; Park, Chun Wook; Lee, Cheol Heon

2011-10-01

365

Accumulation of Recombinant SARS-CoV Spike Protein in Plant Cytosol and Chloroplasts Indicate Potential for Development of Plant-Derived Oral Vaccines  

Microsoft Academic Search

Plants are promising candidates as bioreactors for the produc- tion 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

HONG-YE LI; S ATHISHKUMAR RAMALINGAM; MEE-LEN CHYE

366

New potential therapeutic approach for the treatment of B-Cell malignancies using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles.  

PubMed

Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders. PMID:24098639

Mezzaroba, Nelly; Zorzet, Sonia; Secco, Erika; Biffi, Stefania; Tripodo, Claudio; Calvaruso, Marco; Mendoza-Maldonado, Ramiro; Capolla, Sara; Granzotto, Marilena; Spretz, Ruben; Larsen, Gustavo; Noriega, Sandra; Lucafň, Marianna; Mansilla, Eduardo; Garrovo, Chiara; Marín, Gustavo H; Baj, Gabriele; Gattei, Valter; Pozzato, Gabriele; Núńez, Luis; Macor, Paolo

2013-01-01

367

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. PMID:24098639

Mezzaroba, Nelly; Zorzet, Sonia; Secco, Erika; Biffi, Stefania; Tripodo, Claudio; Calvaruso, Marco; Mendoza-Maldonado, Ramiro; Capolla, Sara; Granzotto, Marilena; Spretz, Ruben; Larsen, Gustavo; Noriega, Sandra; Lucafň, Marianna; Mansilla, Eduardo; Garrovo, Chiara; Marín, Gustavo H.; Baj, Gabriele; Gattei, Valter; Pozzato, Gabriele; Núńez, Luis; Macor, Paolo

2013-01-01

368

Malignancy-Associated Dyslipidemia  

PubMed Central

Cholesterol and triglycerides, important lipid constituents of cell, are essential to carry out several vital physiological functions. Lipids might be associated with cancers because they play a key role in the maintenance of cell integrity. The pathway for cholesterol synthesis may also produce various tumorigenic compounds and cholesterol serves as a precursor for the synthesis of many sex hormones linked to increased risk of various cancers. In some malignant diseases, blood cholesterol undergoes early and significant changes. The mechanism for the link between cancer and cholesterol remains controversial. The dates from studies are confusing because both hypolipidemia and hypercholesterolemia might be connected with malignancy. Not only cancers but also antineoplastic therapies have an influence on lipid profile. There are also dates suggesting that antihyperlipemic drugs might nfluenced malignancy. PMID:21660223

Bielecka-D?browa, Agata; Hannam, Simon; Rysz, Jacek; Banach, Maciej

2011-01-01

369

Human papillomavirus and disease mechanisms: relevance to oral and cervical cancers.  

PubMed

Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy and is a major cause of cancer morbidity and mortality worldwide. Carcinoma of the uterine cervix is the most common female malignancy in the world. While cervical cancer is a worldwide disease, oral cancer has the highest incidence in developing countries, especially among tobacco and alcohol users and betel quid chewers. A strong association of cervical and oral cancer with high-risk human papillomavirus (HPV) 16 and 18 infections underlines the importance of the virus in the pathogenesis of these squamous cell carcinomas. Functionally high-risk HPV infection contributes to carcinogenesis and tumor progression predominantly through the actions of two viral oncogenes, E6 and E7. The E6 and E7 genes have been studied in different patient populations and a number of variants have been described. More than 40 variants have been classified and may be related to differences in progression of squamous intraepithelial lesions. The transcription factor, NFkappaB and its activation pathways are frequently targeted by viruses and aberrant constitutive activation of NFkappaB is frequently found in human tumors of diverse tissue origin. Diet-gene interactions are also likely to contribute considerably to the observed inter-individual variations in HPV associated cancer risk, in response to exposures to the nutritional factors that have the potential to promote or protect against cancer. PMID:16269025

Nair, S; Pillai, M R

2005-11-01

370

Impact of Hormone-Associated Resistance to Activated Protein C on the Thrombotic Potential of Oral Contraceptives: A Prospective Observational Study  

PubMed Central

Introduction The increased thrombotic risk of oral contraceptives (OC) has been attributed to various alterations of the hemostatic system, including acquired resistance to activated protein C (APC). To evaluate to what extent OC-associated APC resistance induces a prothrombotic state we monitored plasma levels of thrombin and molecular markers specific for thrombin formation in women starting OC use. Elevated plasma levels of thrombin have been reported to characterize situations of high thrombotic risk such as trauma-induced hypercoagulability, but have not yet been studied during OC use. Patients and Methods Blood samples were collected prospectively from healthy women (n?=?21) before and during three menstruation cycles after start of OC. APC resistance was evaluated using a thrombin generation-based assay. Plasma levels of thrombin and APC were directly measured using highly sensitive oligonucleotide-based enzyme capture assay (OECA) technology. Thrombin generation markers and other hemostasis parameters were measured additionally. Results All women developed APC resistance as indicated by an increased APC sensitivity ratio compared with baseline after start of OC (p?=?0.0003). Simultaneously, plasma levels of thrombin, prothrombin fragment 1+2, and of thrombin-antithrombin complexes did not change, ruling out increased thrombin formation. APC plasma levels were also not influenced by OC use, giving further evidence that increased thrombin formation did not occur. Conclusions In the majority of OC users no enhanced thrombin formation occurs despite the development of APC resistance. It cannot be ruled out, however, that thrombin formation might occur to a greater extent in the presence of additional risk factors. If this were the case, endogenous thrombin levels might be a potential biomarker candidate to identify women at high thrombotic risk during OC treatment. Large-scale studies are required to assess the value of plasma levels of thrombin as predictors of OC-associated thrombotic risk. PMID:25121606

Müller, Jens; Sukhitashvili, Shorena; Welz, Julia; Kuhn, Walther C.; Oldenburg, Johannes; Rudlowski, Christian; Pötzsch, Bernd

2014-01-01

371

Surveillance for gastrointestinal malignancies  

PubMed Central

Gastrointestinal (GI) malignancies are notorious for frequently progressing to advanced stages even in the absence of serious symptoms, thus leading to delayed diagnoses and dismal prognoses. Secondary prevention of GI malignancies through early detection and treatment of cancer-precursor/premalignant lesions, therefore, is recognized as an effective cancer prevention strategy. In order to efficiently detect these lesions, systemic application of screening tests (surveillance) is needed. However, most of the currently used non-invasive screening tests for GI malignancies (for example, serum markers such as alpha-fetoprotein for hepatocellular carcinoma, and fecal occult blood test, for colon cancer) are only modestly effective necessitating the use of highly invasive endoscopy-based procedures, such as esophagogastroduodenoscopy and colonoscopy for screening purposes. Even for hepatocellular carcinoma where non-invasive imaging (ultrasonography) has become a standard screening tool, the need for repeated liver biopsies of suspicious liver nodules for histopathological confirmation can’t be avoided. The invasive nature and high-cost associated with these screening tools hinders implementation of GI cancer screening programs. Moreover, only a small fraction of general population is truly predisposed to developing GI malignancies, and indeed needs surveillance. To spare the average-risk individuals from superfluous invasive procedures and achieve an economically viable model of cancer prevention, it’s important to identify cohorts in general population that are at substantially high risk of developing GI malignancies (risk-stratification), and select suitable screening tests for surveillance in these cohorts. We herein provide a brief overview of such high-risk cohorts for different GI malignancies, and the screening strategies that have commonly been employed for surveillance purpose in them. PMID:22969223

Tiwari, Ashish K; Laird-Fick, Heather S; Wali, Ramesh K; Roy, Hemant K

2012-01-01

372

[Malignant primary intrathoracic histiocytofibroma].  

PubMed

Malignant primary intrathoracic fibrous histiocytoma (MFH) is a rare tumour: since it was first described in 1979, hardly more than 80 cases have been published. We present a large MFH which had started in the pleura and was intrathoracic. The tumour was typical, being comprised of malignant fibroblastic and histiocytoid cells in storiform arrangement. It was revealed by spinal bone metastases which multiplied over the whole skeleton in spite of chemotherapy. The patient died of cerebral metastasis developed 8 months after the onset of the disease. The cases found in the literature are gathered together and commented. PMID:1338999

Natali, F; Fesselet, J; Jancovici, R; Pons, F; Schill, H; Genero-Gygax, M L; Vaylet, F; Allard, P

1992-01-01

373

Desmoplastic malignant mesothelioma.  

PubMed

Desmoplastic mesothelioma is a rare subtype of diffuse malignant mesothelioma. A 72-year-old woman from East Anatolia presented with chest pain. The images of body positron emission tomography revealed irregular, left pleural thickening involving mediastinal and diaphragmatic surfaces with hypermetabolic characterization. The diagnosis of desmoplastic malignant mesothelioma was confirmed by minithoracotomy and immunohistochemical staining with pan-cytokeratin, cytokeratin 5/6, calretinin, carcinoembryonic antigen, thyroid transcription factor-1, CD15, and HMB-45 on the biopsy specimen. This case is unique in terms of the reporting patient being from a nonendemic area for asbestos-related diseases and in terms of its rare histopathology. PMID:23609252

Baççio?lu, Ay?e; Kaba, Erkan; Ozmen, Sevilay A; Demirci, Munir

2013-04-01

374

MALIGNANT DEGENERATION IN BURN SCARS  

PubMed Central

The malignant potential of burn scars has been recognized since Marjolin's classical description of cancer arising in several types of post-traumatic scars. With improved burn therapy since the last war, there has been a higher survival rate of severe burns with proportionate increase in cancer associated with burn scars. This will create increasing problems of permanent disability and compensation. The younger the patient at the time of the burn, the longer the time required for the cancer to develop. Acute cancer development in burn scars has been reported after a four-week interval. Cancer may develop from six weeks to fifty years or more. The etiology of cancer in burn scars is not known. The most important clinical finding is the fact that most of the burn cancers occur in areas which were not grafted. The most common type of cancer encountered in burn scars is squamous cell carcinoma, which forms in Marjolin ulcers. Basal cell carcinoma may develop in the most superficial of burn scars. Treatment should be directed primarily to prompt and adequate skin grafting in all deep burns in order to prevent malignant degeneration of the burn scars. Once it has developed the treatment is the same as for other malignancies which are not associated with burns. Wide surgical excision with block dissection of the regional lymph nodes when they are involved is the treatment of choice. The prognosis of burn scar cancer is poor, once the process has extended because of early and distant metastasis. ImagesFigure 1.Figure 2.Figure 2.Figure 3.Figure 3.Figure 4. PMID:13691372

Castańares, Salvador

1961-01-01

375

Malignant Catarrhal Fever  

Technology Transfer Automated Retrieval System (TEKTRAN)

Malignant catarrhal fever (MCF) is a frequently fatal viral disease of ruminant species, particularly cattle, bison, and deer. Clinical signs vary between species. Two major epidemiologic types of MCF exist, and are defined by the ruminant species that serve as natural reservoir hosts for infection...

376

Cytoplasmic suppression of malignancy.  

PubMed

Using both normal and transformed rat liver epithelial cells to prepare cytoplasmic hybrids (cybrids) we have found evidence to support the theory that the cytoplasm from a normal cell can suppress tumorigenicity. A unique aspect of this study is that all of the cells utilized, both normal and malignantly transformed, were derived from an original cloned cell. We found that fusing cytoplasts from normal cells to malignantly transformed whole cells resulted in cybrid clones which, when injected into newborn rat pups, isogenic with those from which the cell culture was initiated, yielded tumors in 51% of the animals injected compared to 92% of the animals injected with the tumorigenic parent. Those animals that did develop tumors from the cybrid cells survived longer than those injected with cells from the tumorigenic parent. Thus, the cybrid, formed of cytoplasm from both parents, was less tumorigenic than the malignantly transformed parent cell. When reconstituted cells were prepared by fusing cytoplasts from normal cells with karyoplasts from malignantly transformed cells, a situation in which essentially all of the cytoplasm of the reconstituted cell is derived from normal cells, the tumorigenic phenotype was extinguished. PMID:3654482

Israel, B A; Schaeffer, W I

1987-09-01

377

Malignant adnexal neoplasms  

Microsoft Academic Search

Malignant cutaneous adnexal neoplasms are one of the most challenging areas of dermatopathology. Tumors of the pilosebaceous apparatus can occur as single-lineage neoplasms or may manifest as complex proliferations with multilineal differentiation patterns including not only the germinative component of the hair bulb, the inner or outer root sheath epithelium and the sebaceous gland and duct, but also the sweat

A Neil Crowson; Cynthia M Magro; Martin C Mihm

2006-01-01

378

Malignant tumors of childhood  

SciTech Connect

This book contains 34 papers about malignant tumors. some of the titles are: Invasive Cogenital Mesoblastic Nephroma, Leukemia Update, Unusual Perinatal Neoplasms, Lymphoma Update, Gonadal Germ Cell Tumors in Children, Nutritional Status and Cancer of Childhood, and Chemotherapy of Brain tumors in Children.

Brooks, B.J.

1986-01-01

379

Cytochrome P450 Metabolism of Betel Quid-Derived Compounds: Implications for the Development of Prevention Strategies for Oral and Pharyngeal Cancers  

PubMed Central

Betel quid (BQ) products, with or without tobacco, have been classified by the International Agency for Research on Cancer (IARC) as group I human carcinogens that are associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. There are estimated 600 million BQ users worldwide. In Taiwan alone there are 2 million habitual users (approximately 10% of the population). Oral and pharyngeal cancers result from interactions between genes and environmental factors (BQ exposure). Cytochrome p450 (CYP) families are implicated in the metabolic activation of BQ- and areca nut-specific nitrosamines. In this review, we summarize the current knowledge base regarding CYP genetic variants and related oral disorders. In clinical applications, we focus on cancers of the oral cavity and pharynx and OPMDs associated with CYP gene polymorphisms, including CYP1A1, CYP2A6, CYP2E1, and CYP26B1. Our discussion of CYP polymorphisms provides insight into the importance of screening tests in OPMDs patients for the prevention of oral and pharyngeal cancers. Future studies will establish a strong foundation for the development of chemoprevention strategies, polymorphism-based clinical diagnostic tools (e.g., specific single-nucleotide polymorphism (SNP) “barcodes”), and effective treatments for BQ-related oral disorders. PMID:23983642

Lin, Che-Yi; Ting, Chun-Chan; Liang, Shih-Shin; Huang, Shu-Hung; Liu, Hsiu-Yueh; Ko, Edward Cheng-Chuan

2013-01-01

380

Oral biofilms, periodontitis, and pulmonary infections  

PubMed Central

Bacteria from the oral biofilms may be aspirated into the respiratory tract to influence the initiation and progression of systemic infectious conditions such as pneumonia. Oral bacteria, poor oral hygiene, and periodontitis seem to influence the incidence of pulmonary infections, especially nosocomial pneumonia episodes in high-risk subjects. Improved oral hygiene has been shown to reduce the occurrence of nosocomial pneumonia, both in mechanically-ventilated hospital patients and non-ventilated nursing home residents. It appears that oral colonization by potential respiratory pathogens, possibly fostered by periodontitis, and possibly by bacteria specific to the oral cavity or to periodontal diseases contribute to pulmonary infections. Thus, oral hygiene will assume an even more important role in the care of high-risk subjects – patients in the hospital intensive care and the elderly. The present paper critically reviews the recent literature on the effect of oral biofilms and periodontitis on pneumonia. PMID:17944664

Paju, S; Scannapieco, FA

2008-01-01

381

Diagnostic Concordance Characteristics of Oral Cavity Lesions  

PubMed Central

Purpose. The objective of this study was to evaluate the diagnostic concordance characteristics of oral cavity lesions by comparing the clinical diagnosis of the lesions with the histopathologic diagnosis. Material and Method. A retrospective analysis was conducted on the patients, who were admitted with oral cavity pathology and underwent biopsy procedure between 2007 and 2011. The oral cavity lesions were classified into 6 different groups as odontogenic cysts, nonodontogenic cysts, odontogenic tumors, nonodontogenic tumors, malignant tumors, and precancerous lesions in accordance with the 2005 WHO classification. The diagnoses were also recategorized into 3 groups expressing prognostic implications as benign, precancerous, and malignant. The initial clinical diagnoses were compared with the histopathologic diagnoses. Data were analyzed statistically. Results. A total of 2718 cases were included. Histopathologic diagnosis did not match the clinical diagnosis in 6.7% of the cases. Nonodontogenic tumors and malignant tumors had the highest misdiagnosis rates (11.5% and 9%, resp.), followed by odontogenic tumors (7.7%), precancerous lesions (6.9%), and odontogenic cysts (4.4%). Clinicians were excelled in diagnosis of benign and precancerous lesions in clinical setting. Conclusion. The detailed discordance characteristics for each specific lesion should be considered during oral pathology practice to provide early detection without delay. PMID:24453906

Tatli, Ufuk; Erdo?an, Özgür; U?uz, Aysun; Üstün, Yakup; Sertdem?r, Ya?ar

2013-01-01

382

Oral Cancer  

MedlinePLUS

... treatment by an SLP are important to restore speech intelligibility and swallowing skills. Treatment often includes helping people get used to the differences in the size, shape, and feel of their mouth. The SLP will ... how to produce speech sounds more clearly. Oral exercises help the client ...

383

Oral tolerance  

Microsoft Academic Search

The ability of the mucosal immune system to distinguish between harmful and harmless antigens is essential for mounting protective immune responses and preventing the induction of mucosal pathology yet the basis for this remains unclear. As fed antigen can also exert systemic effects understanding oral tolerance and priming will also have important consequences for therapy and vaccination. Here we will

P Garside; A. McI Mowat

2001-01-01

384

Oral Care  

Microsoft Academic Search

Adequate dental and oral hygiene may become a challenge for all users and especially for elderly people and young children because of their limited motor skills. The same holds true for patients undergoing\\/recovering from chemo-\\/radiotherapy with accompanying sensitive mucosal conditions. Poor dental hygiene can result in tooth decay, gingivitis, periodontitis, tooth loss, bad breath (halitosis), fungal infection and gum diseases.

Irčne Hitz Lindenmüller; J. Thomas Lambrecht

2011-01-01

385

The clinical effectiveness of reflectance optical spectroscopy for the in vivo diagnosis of oral lesions  

PubMed Central

Optical spectroscopy devices are being developed and tested for the screening and diagnosis of oral precancer and cancer lesions. This study reports a device that uses white light for detection of suspicious lesions and green–amber light at 545?nm that detect tissue vascularity on patients with several suspicious oral lesions. The clinical grading of vascularity was compared to the histological grading of the biopsied lesions using specific biomarkers. Such a device, in the hands of dentists and other health professionals, could greatly increase the number of oral cancerous lesions detected in early phase. The purpose of this study is to correlate the clinical grading of tissue vascularity in several oral suspicious lesions using the Identafi® system with the histological grading of the biopsied lesions using specific vascular markers. Twenty-one patients with various oral lesions were enrolled in the study. The lesions were visualized using Identafi® device with white light illumination, followed by visualization of tissue autofluorescence and tissue reflectance. Tissue biopsied was obtained from the all lesions and both histopathological and immunohistochemical studies using a vascular endothelial biomarker (CD34) were performed on these tissue samples. The clinical vascular grading using the green–amber light at 545?nm and the expression pattern and intensity of staining for CD34 in the different biopsies varied depending on lesions, grading ranged from 1 to 3. The increase in vascularity was observed in abnormal tissues when compared to normal mucosa, but this increase was not limited to carcinoma only as hyperkeratosis and other oral diseases, such as lichen planus, also showed increase in vascularity. Optical spectroscopy is a promising technology for the detection of oral mucosal abnormalities; however, further investigations with a larger population group is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant lesions. PMID:25059250

Messadi, Diana V; Younai, Fariba S; Liu, Hong-Hu; Guo, Gao; Wang, Cun-Yu

2014-01-01

386

Nano-bio-chip sensor platform for examination of oral exfoliative cytology.  

PubMed

Oral cancer is a deadly and disfiguring disease that could greatly benefit from new diagnostic approaches enabling early detection. In this pilot study, we describe a nano-bio-chip (NBC) sensor technique for analysis of oral cancer biomarkers in exfoliative cytology specimens, targeting both biochemical and morphologic changes associated with early oral tumorigenesis. Here, oral lesions from 41 dental patients, along with normal epithelium from 11 healthy volunteers, were sampled using a noninvasive brush biopsy technique. Specimens were enriched, immunolabeled, and imaged in the NBC sensor according to previously established assays for the epidermal growth factor receptor (EGFR) biomarker and cytomorphometry. A total of 51 measurement parameters were extracted using custom image analysis macros, including EGFR labeling intensity, cell and nuclear size, and the nuclear-to-cytoplasmic ratio. Four key parameters were significantly elevated in both dysplastic and malignant lesions relative to healthy oral epithelium, including the nuclear area and diameter (P < 0.0001), the nuclear-to-cytoplasmic ratio (P < 0.0001), and EGFR biomarker expression (P < 0.03). Further examination using logistic regression and receiver operating characteristic curve analyses identified morphologic features as the best predictors of disease (area under the curve < or =0.93) individually, whereas a combination of all features further enhanced discrimination of oral cancer and precancerous conditions (area under the curve, 0.94) with high sensitivity and specificity. Further clinical trials are necessary to validate the regression model and evaluate other potential biomarkers, but this pilot study supports the NBC sensor technique as a promising new diagnostic tool for early detection of oral cancer, which could enhance patient care and survival. PMID:20332305

Weigum, Shannon E; Floriano, Pierre N; Redding, Spencer W; Yeh, Chih-Ko; Westbrook, Stephen D; McGuff, H Stan; Lin, Alan; Miller, Frank R; Villarreal, Fred; Rowan, Stephanie D; Vigneswaran, Nadarajah; Williams, Michelle D; McDevitt, John T

2010-04-01

387

Sinonasal malignancies of neuroendocrine origin.  

PubMed

The sinonasal malignancies of putative neuroendocrine origin-esthesioneuroblastoma, sinonasal neuroendocrine carcinoma, sinonasal undifferentiated carcinoma, and sinonasal small cell carcinoma-are uncommon malignancies that frequently present with locally advanced disease. Pathologic distinction between these entities can be difficult, but is important to guide management. These malignancies require complex multimodality treatment and are best managed by multidisciplinary teams in major centers that have expertise in sinonasal malignancies. PMID:19010275

Rischin, Danny; Coleman, Andrew

2008-12-01

388

Imaging of uncommon esophageal malignancies.  

PubMed

Malignant esophageal neoplasms other than squamous cell carcinoma and adenocarcinoma are uncommon and include endocrine tumors, lymphoid malignancies, melanoma, malignant stromal tumors, and secondary tumors (metastases). Imaging, though not diagnostic in many cases, helps in selecting the appropriate treatment strategy by determining the anatomic extent of the tumor and locoregional and distant spread. In this article, we provide a comprehensive review of the imaging features of these uncommon esophageal malignancies. PMID:24635682

Tirumani, H; Rosenthal, M H; Tirumani, S H; Shinagare, A B; Krajewski, K M; Ramaiya, N H

2014-03-17

389

Oral care.  

PubMed

Adequate dental and oral hygiene may become a challenge for all users and especially for elderly people and young children because of their limited motor skills. The same holds true for patients undergoing/recovering from chemo-/radiotherapy with accompanying sensitive mucosal conditions. Poor dental hygiene can result in tooth decay, gingivitis, periodontitis, tooth loss, bad breath (halitosis), fungal infection and gum diseases. The use of a toothbrush is the most important measure for oral hygiene. Toothbrushes with soft bristles operated carefully by hand or via an electric device help to remove plaque and to avoid mucosal trauma. A handlebar with a grip cover can be helpful for manually disabled patients or for those with reduced motor skills. In case of oral hygiene at the bedside or of patients during/after chemo-/radiotherapy a gauze pad can be helpful for gently cleaning the teeth, gums and tongue. The use of fluoride toothpaste is imperative for the daily oral hygiene. Detergents such as sodium lauryl sulphate improve the cleaning action but may also dehydrate and irritate the mucous membrane. The use of products containing detergents and flavouring agents (peppermint, menthol, cinnamon) should therefore be avoided by bedridden patients or those with dry mouth and sensitive mucosa. Aids for suitable interdental cleaning, such as dental floss, interdental brushes or dental sticks, are often complicated to operate. Their correct use should be instructed by healthcare professionals. To support dental care, additional fluoridation with a fluoride gel or rinse can be useful. Products further containing antiseptics such as chlorhexidine or triclosan reduce the quantity of bacteria in the mouth. For patients undergoing or having undergone radio-/chemotherapy, a mouthwash that concomitantly moisturizes the oral mucosa is advisable. PMID:21325845

Hitz Lindenmüller, Irčne; Lambrecht, J Thomas

2011-01-01

390

Chemotherapy of advanced malignant teratomas.  

PubMed Central

Between 1977 and November 1979 we have treated 53 patients with malignant teratomas (43 males, 10 females). Thirty (70%) out of the 43 male patients had advanced and bulky disease at the time of presentation. Using different drug combinations in a sequential manner as described below, results are as follows: of the initial 33 male patients, 22 (67%) have discontinued treatment (mean 9.5 months). Nineteen have responded completely and 3 have static computed tomography (CT) nodules. Life-table analysis projects a survival of 66% (analysis at 1 December 1979). Nine out of 10 ovarian teratoma patients are alive. Adverse prognostic factors at the start of treatment were recognized in 9/10 male patients and the 1 female patient who have died. Although the survival of patients with malignant teratomas has improved dramatically, there are still problems with drug resistance in patients with very advanced disease. Patients with these tumours should continue to be treated in centres specializing in managing what has now become a potentially curable disease in most cases. PMID:7426343

Newlands, E. S.; Begent, R. H.; Kaye, S. B.; Rustin, G. J.; Bagshawe, K. D.

1980-01-01

391

A Rare Malignant Triton Tumor  

Microsoft Academic Search

Malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation, malignant triton tumor, has a rare incidence. We report such a case in a 40-year-old male who presented with a mass over the buttock. He was a previously diagnosed case of neurofibroma in the same area. Histomorphology supported by immunostaining with S-100 protein confirmed the diagnosis. Malignant triton tumor has a poor

Kalpalata Tripathy; Rabinarayan Mallik; Aparajita Mishra; Debiprasad Misra; Niranjan Rout; Padmalaya Nayak; Sagarika Samantray; Jayshree Rath

2010-01-01

392

Plexiform neurofibromatosis involving face and oral cavity.  

PubMed

Plexiform neurofibromas (PNFs) are one of the most common and debilitating complications of neurofibromatosis type I (NF-I). They account for substantial morbidity, disfigurement, functional impairment and are life threatening. PNFs can also be subjected to transformation into malignant peripheral nerve sheath tumor (MPNST). This complication is refractory to treat due to paucity of effective therapies for malignant soft tissue sarcomas in general and also the delay in diagnosis from a preexisting tumor. We report a case of PNF of face involving oral cavity with literature review. PMID:24959050

Jayachandran, Dorairaj; Sunantha, Selvaraj; Gopalaiah, Hema; Veeraraghavan, Gajendra

2014-01-01