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Sample records for oral potentially malignant

  1. Patient delay for potentially malignant oral symptoms.

    PubMed

    Scott, Suzanne; McGurk, Mark; Grunfeld, Elizabeth

    2008-04-01

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

  2. Candida in potentially malignant oral disorders

    PubMed Central

    Sankari, S. Leena; Gayathri, K.; Balachander, N.; Malathi, L.

    2015-01-01

    Oro-pharyngeal cancer is a significant component in the global burden of cancer. A considerable proportion of oral squamous carcinomas develop from preexsiting potentially malignant disorder of the oral cavity. The term potentially malignant oral disorders (PMD) were proposed for the precancerous lesions and conditions by World Health Organization in 2007. PMD are considered an in-between clinical state, which showed increased risk for cancer development. Etiology of PMD is multifactorial. Tobacco and alcohol are the major risk factors. In recent years, role of candidal infection is recognized as a significant factor in the development of PMD. There is an enduring discussion whether Candida infection can be a cause of PMD or a superimposed infection in a preexisting lesion. This article highlights the association between Candida and PMD. PMID:26015698

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  6. Qat Chewing and Risk of Potentially Malignant and Malignant Oral Disorders: A Systematic Review.

    TOXLINE Toxicology Bibliographic Information

    El-Zaemey S; Schüz J; Leon ME

    2015-07-01

    BACKGROUND: Qat (also known as Khat, Kat and Miraa) is a green-leaved plant (Catha edulis). It is a shrub indigenous to Yemen and certain parts of eastern Africa. Chewing the leaves, which have sympathomimetic and euphoric effects, has been documented in many countries and increased with worldwide migration. The effect of long-term chewing Qat on the oral cavity is unknown.OBJECTIVE: A systematic review was performed to identify any associations between Qat chewing and the occurrence of potentially malignant and malignant oral disorders.METHODS: Medline and the Web of Science were searched for articles published before May 2014 without limits with regard to publication date and language.RESULTS: From a total of 890 papers identified, 17 English papers reported potentially malignant or malignant oral disorders and Qat chewing. One additional paper in Arabic language was identified from reviewing the list of references of eligible papers. It was found that exposure to Qat may be associated with potentially malignant and malignant oral disorders, but methodological issues, such as inadequate study design, sample size, selection of study subjects, clinical evaluations of outcome and limited adjustment for confounders, limit the strength of the evidence base in this area.CONCLUSION: The association between Qat chewing and potentially malignant and malignant oral disorders remains debatable and requires further investigations.

  7. Frequent gene deletions in potentially malignant oral lesions.

    PubMed Central

    Emilion, G.; Langdon, J. D.; Speight, P.; Partridge, M.

    1996-01-01

    Some oral cancers are preceded by premalignant lesions which include leucoplakia and erythroplakia. At present there are no reliable markers to identify lesions that may progress to malignancy. We have analysed 30 potentially malignant oral lesions for deletions at chromosomal regions that harbour tumour-suppressor genes for oral cancer. A total of 16 of 30 cases (53%) showed loss of heterozygosity (LOH) or allele imbalance at TP53, DCC, 3p21.3-22.1 or 3p12.1-13. These genetic alterations were detected in dysplastic lesions but not in histologically normal mucosa and may be early events in the carcinogenic process. A total of 64% of dysplastic lesions that recurred during the study showed LOH or allele imbalance in the initial biopsy and the number of genetic abnormalities increased in the tumours that developed. This type of molecular profiling may help to identify patients with lesions that may recur or acquire additional genetic events and progress to malignancy. Images Figure 2 PMID:8611386

  8. Malignant transformation of oral potentially malignant disorders in males: a retrospective cohort study

    PubMed Central

    2009-01-01

    Background Oral squamous cell carcinoma could be preceded by clinically evident oral potentially malignant disorders (OPMDs). Transformation of OPMDs to cancer has been studied in several population groups. It is difficult to undertake comparisons across populations due to variations in the methods of computation of malignancy rates among different studies. The aim of our study was to estimate the rate of malignant transformation of OPMDs taking into account the duration of follow-up and to identify the significant factors indicative of malignant potential. Methods A total of 148 male patients with OPMDs were included. They were selected among all consecutive subjects registered at the maxillofacial clinic at a medical hospital in Kaohsiung, Taiwan. The mean follow up period was 37.8 months. Results The malignant transformation rate was highest in subjects diagnosed with oral epithelial dysplasia. In this group the transformation rate was 7.62 per 100 persons-year. The rate in the group with verrucous hyperplasia (VH) was 5.21 per 100 persons-year, and in those with hyperkeratosis or epithelial hyperplasia was 3.26 per 100 persons-year. The anatomical site of OPMDs was the only statistically significant variable associated with malignancy. The hazard rate ratio (HRR) was 2.41 times for tongue lesions when compared with buccal lesions. Conclusion The reported discrepancies of malignant transformation of OPMDs involve the follow-up time to cancer development and hence it is preferable to use a time-to-event estimation for comparisons. We found that malignant transformation of OPMDs involving the tongue was significantly higher than in other anatomical subsites after adjusting for the clinicopathological type or lifestyle factors at diagnosis. PMID:19640311

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. Expression of p63 in potentially malignant and malignant oral lesions

    PubMed Central

    Sinha, Anju; Chandra, Shaleen; Raj, Vineet; Zaidi, Iram; Saxena, Shikha; Dwivedi, Ruby

    2015-01-01

    Background p63, a member of p53 family, known to be expressed in embryonic tissues and basal regenerative layers of many epithelial tissues in the adult, is also expressed in various benign and malignant lesions of body including lesions of oral cavity. To evaluate the expression of p63 and compare the expression qualitatively and quantitatively in normal buccal mucosa, epithelial dysplasia, oral submucous fibrosis (OSMF), and oral squamous cell carcinoma (OSCC). Methods The study material consisted of 45 archival cases which were divided into Group I with 5 cases of normal buccal mucosa, Group II with 15 cases of epithelial dysplasia, and Group III with 10 cases of OSMF and 15 cases of OSCC. Immunohistochemical expression of p63 was assessed by using mean, standard deviation, and analysis of variance. Results Overexpression of p63 was seen in epithelial dysplasia, OSMF, and squamous cell carcinoma with an increased suprabasal expression in cases of epithelial dysplasia. The mean labeling index (LI) of p63 was found to be in increasing order from normal oral mucosa (33.75%), OSMF (57.37%), epithelial dysplasia (63.87%) to squamous cell carcinoma (69.76%). Conclusion The results suggest a possible role of p63 in oral carcinogenesis, and an increased LI as well as increased suprabasal expression of this gene in dysplastic lesions may have a potential to be utilized as a marker for premalignancy. PMID:26605141

  12. Gain of hTERC: a genetic marker of malignancy in oral potentially malignant lesions.

    PubMed

    Dorji, Tshering; Monti, Valentina; Fellegara, Giovanni; Gabba, Silvia; Grazioli, Vittorio; Repetti, Elena; Marcialis, Chiara; Peluso, Sergio; Di Ruzza, Davide; Neri, Fabrizio; Foschini, Maria P

    2015-09-01

    Oral squamous cell carcinoma (OSCC) is the most common oral cancer, and major efforts is being made to identify molecular markers capable to differentiate oral potentially malignant lesions (OPMLs) with indolent course from lesions with aggressive behavior. We undertook a study to evaluate if gain of the human telomerase RNA component (hTERC) gene in OPMLs could indicate lesions at high risk of developing OSCC. The study was performed on 30 OPMLs with long-term follow-up using a dual-color interphase fluorescence in situ hybridization (FISH) for hTERC status. Progression to malignancy was observed in 9 of 10 cases harboring hTERC gain and in 1 of 20 cases retaining a normal copy number of hTERC (P < .0001). Combining morphological grading and FISH analysis, all the cases with high-grade squamous intraepithelial lesion or carcinoma in situ harboring hTERC amplification progressed to OSCC, whereas none of the low-grade squamous intraepithelial lesions without hTERC gain progressed. Intermediate situations occurred. The data suggest that precise morphological evaluation together with FISH assessment for hTERC gain might pave the way to stratify OPMLs into high-risk and low-risk categories and could be helpful in selecting the most appropriate treatment. PMID:26170010

  13. Evaluation of cell proliferation in malignant and potentially malignant oral lesions

    PubMed Central

    Madan, Mani; Chandra, Shaleen; Raj, Vineet; Madan, Rohit

    2015-01-01

    Aims: To evaluate the cell proliferation rate by the expression of proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizing region (AgNOR) counts and to assess its usefulness as a marker for malignant potential in oral epithelial lesions. Materials and Methods: The study group included 30 cases of leukoplakia, 15 nondysplastic (NDL), 15 dysplastic (DL), 15 cases of oral squamous cell carcinoma (OSCC) and 5 cases of normal oral mucosa. Formalin fixed paraffin embedded tissues were subjected to immunohistochemical staining for PCNA and AgNOR technique. The PCNA labeling index (LI) and the AgNOR dots were evaluated for the entire sample. Statistical Analysis Used: ANOVA, Tukey honestly significant difference, Pearson's correlation. Results: In this study, the AgNOR count of OSCC was lower than the DL lesions moreover the AgNOR counts were found to be higher in normal mucosa as compared to the DL and the NDL epithelium. The study results also showed that the mean AgNOR count failed to distinguish between DL and NDL lesions. Overall we observed increased PCNA expression from normal epithelium to NDL to DL lesion. Conclusions: Based on the findings of the present study on oral epithelial precancerous and cancerous lesions we conclude that mean AgNOR count alone cannot be a valuable parameter to distinguish between the normal, NDL, DL epithelium and OSCC but, on the other hand, we found out that PCNA can be a useful biomarker for delineating normal epithelium from DL epithelium and OSCC.

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

    PubMed Central

    Mortazavi, Hamed; Baharvand, Maryam; Mehdipour, Masoumeh

    2014-01-01

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

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

    PubMed

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

    2015-08-01

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

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

    PubMed Central

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

    2016-01-01

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

  17. Increased nuclear ?-catenin expression in oral potentially malignant lesions: A marker of epithelial dysplasia

    PubMed Central

    Rojas-Alcayaga, Gonzalo; Maturana, Andrea; Aitken, Juan-Pablo; Rojas, Carolina; Ortega, Ana-Verónica

    2015-01-01

    Background Deregulation of ?-catenin is associated with malignant transformation; however, its relationship with potentially malignant and malignant oral processes is not fully understood. The aim of this study was to determine and compare the nuclear ?-catenin expression in oral dysplasia and oral squamous cell carcinoma (OSCC). Material and Methods Cross sectional study. Immunodetection of ?-catenin was performed on 72 samples, with the following distribution: 21 mild dysplasia, 12 moderate dysplasia, severe dysplasia 3, 36 OSCC including 19 well differentiated, 15 moderately differentiated and 2 poorly differentiated. Through microscopic observation the number of positive cells per 1000 epithelial cells was counted. For the statistical analysis, the Kruskal Wallis test was used. Results Nuclear expression of ?-catenin was observed in all samples with severe and moderate dysplasia, with a median of 267.5, in comparison to mild dysplasia whose median was 103.75. Only 10 samples (27.7%) with OSCC showed nuclear expression, with statistically significant differences between groups (p < 0.05). Conclusions Our results are consistent with most of the reports which show increased presence of ?-catenin in severe and moderate dysplasia compared to mild dysplasia; however the expression of nuclear ?-catenin decreased after starting the invasive neoplastic process. This suggests a role for this protein in the progression of dysplasia and early malignant transformation to OSCC. Immunodetection of ?-catenin could be a possible immune marker in the detection of oral dysplasia. Key words:Oral squamous cell carcinoma (OSCC), ?-catenin, oral dysplasia. PMID:26241451

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

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

    2009-01-01

    Background Oral squamous cell carcinoma (OSCC) is one of the most common forms of cancer associated with the presence of precancerous oral leukoplakia. Given the poor prognosis associated with oral leukoplakia, and the difficulties in distinguishing it from cancer lesions, there is an urgent need to elucidate the molecular determinants and critical signal pathways underlying the malignant transformation of precancerous to cancerous tissue, and thus to identify novel diagnostic and therapeutic target. Results We have utilized two dimensional electrophoresis (2-DE) followed by ESI-Q-TOF-LC-MS/MS to identify proteins differentially expressed in six pairs of oral leukoplakia tissues with dysplasia and oral squamous cancer tissues, each pair was collected from a single patient. Approximately 85 differentially and constantly expressed proteins (> two-fold change, P < 0.05) were identified, including 52 up-regulated and 33 down-regulated. Gene ontological methods were employed to identify the biological processes that were over-represented in this carcinogenic stage. Biological networks were also constructed to reveal the potential links between those protein candidates. Among them, three homologs of proteosome activator PA28 a, b and g were shown to have up-regulated mRNA levels in OSCC cells relative to oral keratinocytes. Conclusion Varying levels of differentially expressed proteins were possibly involved in the malignant transformation of oral leukoplakia. Their expression levels, bioprocess, and interaction networks were analyzed using a bioinformatics approach. This study shows that the three homologs of PA28 may play an important role in malignant transformation and is an example of a systematic biology study, in which functional proteomics were constructed to help to elucidate mechanistic aspects and potential involvement of proteins. Our results provide new insights into the pathogenesis of oral cancer. These differentially expressed proteins may have utility as useful candidate markers of OSCC. PMID:19691830

  20. Prevalence of oral potentially malignant disorders in workers of Udupi taluk

    PubMed Central

    Kumar, Yeturu Sravan; Acharya, Shashidhar; Pentapati, Kalyana Chakravarthy

    2015-01-01

    Objective: The objective was to assess the prevalence and risk factors of oral potentially malignant disorders (PMD) among industrial workers of Udupi taluk, Karnataka. Materials and Methods: The sample consisted of industrial workers aged >18 years from randomly selected industries in Udupi Taluk. A self-administered questionnaire was given to the participants to assess sociodemographic factors and abusive habits (Tobacco, Alcohol, and Betel quid) followed by clinical oral examination by single trained and calibrated examiner. Results: A total of 396 completed all steps of the survey and were included for analysis. A total of 14, 11.4, and 14.4% were tobacco, alcohol, and betel quid users, respectively. A total of 8.6% (n = 34) have at least one PMD. A significantly higher number of participants with single (11.4%) or combined habits (60.4%) had oral lesions while none of the participants without habits reported any oral lesions (P = 0.001). Conclusion: Prevalence of abusive habits and oral premalignant lesions or conditions was substantial among the workers. The cause and effect relationship and dose-response were also shown to be significantly associated. Prevention and early diagnosis through workplace screening are the major cornerstones for the control of oral cancer.

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

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

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

    PubMed

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

    2014-06-01

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

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

    PubMed Central

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

    2016-01-01

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

  4. Fibrotic Effects of Arecoline N-Oxide in Oral Potentially Malignant Disorders.

    PubMed

    Kuo, Tzer-Min; Luo, Shun-Yuan; Chiang, Shang-Lun; Yeh, Kun-Tu; Hsu, Hui-Ting; Wu, Cheng-Tien; Lu, Chi-Yu; Tsai, Ming-Hsui; Chang, Jan-Gowth; Ko, Ying-Chin

    2015-06-24

    The metabolites of environmental chemicals play key roles in carcinogenesis. Areca nut is strongly associated with the development of oral potentially malignant disorders (OPMD) or cancer. The main alkaloid in the areca nut is arecoline, which is highly cytotoxic and genotoxic. Arecoline N-oxide, a metabolite of areca nut alkaloids, which has been identified in animal urine, has been shown to induce mutagenicity in bacteria. In this study, it was found that its protein adduct could be detected in oral keratinocytes treated with areca nut extract. Increased collagen expression and severity of squamous hyperplasia were observed in arecoline N-oxide treated mice. In cultured oral fibroblasts, arecoline N-oxide showed stronger effects on the increase of fibrotic related genes including TGF-beta1, S100A4, MMP-9, IL-6, and fibronectin and a decrease of E-cadherin as compared with arecoline. Finally, arecoline N-oxide stimulation effectively increased the DNA damage marker, gamma-H2A.X, both in vitro and in vivo. Taken together, these results indicate that arecoline N-oxide shows a high potential for the induction of OPMD. PMID:26061808

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

    PubMed Central

    DeCoro, Michael; Wilder-Smith, Petra

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

    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 20 years. 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

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

    PubMed

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

    2014-12-01

    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

  9. Immunoexpression of tenascin as a predictor of the malignancy potential of oral leukoplakia associated with a tobacco habit.

    PubMed

    Mane, D R; Bhat, K; Kale, A D; Hallikerimath, S

    2015-10-01

    Oral leukoplakia is a morphological alteration of tissue that is an early indicator for malignancy. Tenascin (TN) is a large hexameric extracellular matrix (ECM) protein with anti-adhesive properties that fosters cell migration during development, wound healing and tissue remodeling; it is present in small amounts in adult tissues. Overexpression of TN in a pathological condition may be either a cause or a consequence of the disease. We evaluated the efficacy of TN for early prediction of tobacco-associated oral cancers. We studied retrospectively 95 cases of oral leukoplakia, including mild, moderate and severe cases, using immunohistochemistry for TN. We evaluated the intensity, area and pattern of TN expression. Greater intensity and area of TN expression was observed in mild and severe dysplasia than in moderate dysplasia. Most cases showed a reticular pattern of expression, especially in mild and moderate dysplasia; a fibrillar pattern was more evident in severe dysplasia. We also observed homogeneous expression pattern in some cases. TN is a marker for dysplastic changes in epithelium and its expression may be helpful for predicting the malignancy potential of tobacco-associated oral leukoplakia. PMID:25839195

  10. Leuloplakia - Review of A Potentially Malignant Disorder

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  13. Leukoplakia: A short review on malignant potential

    PubMed Central

    Masthan, K. M. K.; Babu, N. Aravindha; Sankari, S. Leena; Priyadharsini, C.

    2015-01-01

    Oral leukoplakia is one of the most common potentially malignant disorders. Right diagnosis of potentially malignant disorders may help to prevent these lesions from malignant transformation. Proper understanding, recognizing, identification and differentiating these lesions from normal mucosa are necessary for proper treatment. PMID:26015699

  14. Assessment of ABO blood grouping and secretor status in the saliva of the patients with oral potentially malignant disorders

    PubMed Central

    Rai, Pragati; Acharya, Swetha; Hallikeri, Kaveri

    2015-01-01

    Background: Secretor status may possibly be one of the factors in the etiopathogenesis of oral precancerous lesions and subsequently cancer. Studies have shown the relationship between the pathogenesis of disease and secretor status. They have made known that secretor status is a possible factor influencing disease status. Studies have revealed the association between blood groups and specific diseases. Aims: To assess any association of ABO blood grouping with oral potentially malignant disorders (OPMDs) and to examine whether there is any difference in the saliva secretor status in the patients with OPMDs and healthy controls. Materials and Methods: The study consisted of 90 subjects, with 45 patients assigned to two groups (a) Patients with potentially malignant disorders and (b) healthy controls. ABO blood grouping was done and 1 ml of unstimulated saliva was collected in a sterile test tube. The Wiener agglutination test was performed to analyze the secretor status in both the groups. Chi-square test and odd ratio were used to assess the relationship between ABO blood group and OPMDs. Chi-square test was performed to assess the relationship between secretor status and OPMDs. Probability level was fixed at <0.05. Results: The results demonstrated a statistically significant relation between OPMDs and secretor status (P = 0.00). Eighty-seven percent of patients with OPMDs were nonsecretors, while in the control group sixteen percent of them were nonsecretors. There was no statistically significant relationship between ABO blood groups and OPMDs (P > 0.05). Conclusions: The study confirms the inability to secrete blood group antigens in the saliva of patients with OPMDs which could be regarded as a host risk factor. Results could not propose a relationship between ABO blood group and OPMDs. PMID:26604491

  15. Between-Lesion Discrepancies in Terms of Dysplasia, Cell Turnover and Diagnosis in Patients with Multiple Potentially Malignant Oral Lesions

    PubMed Central

    Lucio, Montebugnoli; Andrea, Gabusi; Bartolomeo, Gissi Davide; Fabio, Cervellati; Dora, Servidio

    2013-01-01

    Objective: The present study assessed patients with multiple oral lesions to evaluate the mis-estimation rate in terms of diagnosis and risk of malignant transformation when only one biopsy is performed. Study Design: Thirty-five patients presenting at least two white and/or red lesions in different oral mucosa sites with a final diagnosis of leuko/erythroplakias or lichenoid lesions were included, for a total of 70 biopsies. Results: Nineteen patients (54%) had at least one between-lesion discrepancy considering the presence/absence of dysplasia (10 patients), normal/high cell turnover (13 patients) or diagnosis (5 patients). Discrepancies were not related to clinical aspect or within-patient similarity of lesions. Conclusions: Multiple oral lesions in the same patient can significantly differ in terms of dysplasia, high cell turnover and, even diagnosis. Multiple biopsies are imperative and diagnosis as well as risk of malignant transformation should be formulated for each single lesion rather than for each individual patient. PMID:24363787

  16. Noninvasive imaging of oral premalignancy and malignancy

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  17. Oral malignant melanoma: a rare case with unusual clinical presentation

    PubMed Central

    Ali, Elneel Ahmed Mohamed; Karrar, Musadak Ali; El-Siddig, Abeer Abdalla; Zulfu, Azza

    2015-01-01

    Primary Oral malignant melanoma is a rare tumor with an indigent prognosis. This is a case report of 47-year-old Sudanese female diagnosed as Oral malignant melanoma of the mandible with an unusual pattern of growth and clinical presentation. Furthermore, a possibility of intraosseous origin is suggested. PMID:26848360

  18. Morphometry As a Diagnostic Tool for Potentially Malignant Lesions

    PubMed Central

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

    2015-01-01

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

  19. Malignant Conversion of Oral Submucous Fibrosis in Surgically Treated Case

    PubMed Central

    Arora, Rajendra; Adwani, Dwarkadas; Naphade, Milind; Qureshi, Abdul Qahar

    2014-01-01

    Oral submucous fibrosis (OSMF) is an insidious chronic disease affecting any part of the oral cavity and sometimes the pharynx with epithelial atrophy leading to stiffness of the oral mucosa, causing trismus and inability to eat. However a more serious complication of this disease is the risk of the development of oral carcinoma. We reported the histopathologically proven case of OSMF with initial interincisal mouth opening 2mm which was treated surgically with nasolabial flap technique but failed to follow up and could not do active mouth opening exercises. Malignant conversion of OSMF was seen in this case. This is required to assess the progress and evaluate any malignant transformation at the earliest. So, the importance of active co-operation and frequent follow up cannot be overemphasized. The purpose of this study is to emphasize the importance of regular follow up and frequent biopsies to facilitate oral examination and to check any malignant conversion after the surgery. PMID:25478469

  20. Myeloid cell leukemia-1 is a molecular indicator for malignant transformation of oral lichen planus

    PubMed Central

    SHIN, JI-AE; SEO, JAE-MIN; OH, SEJUN; CHO, SUNG-DAE; LEE, KYUNG-EUN

    2016-01-01

    Oral lichen planus (OLP), characterized by a chronic mucocutaneous inflammatory condition, is a common disease of the oral cavity. Retrospective and prospective epidemiological data suggest that OLP is considered to have malignant potential. However, it is unclear as to which types of molecules may cause malignant transformation of OLP. In the present study, the presence of myeloid cell leukemia-1 (Mcl-1) and B-cell lymphoma-2 (Bcl-2) was studied by western blot analysis in 11 OLP and three normal oral mucosa (NOM) samples and in two human oral cancer cell lines. The functional role of Mcl-1 in oral cancer cells was analyzed using a trypan blue exclusion assay and soft agar assay. Mcl-1 was strongly expressed in the OLP and the two oral cancer cell lines compared with NOM, whereas Bcl-2 was not. Sorafenib and mithramycin A decreased cell viability in MC-3 and HSC-3 oral cancer cells and at same concentration they reduced the expression level of Mcl-1 in the two cell lines. The two chemicals affected Mcl-1 protein and significantly inhibited neoplastic cell transformation in the two cell lines. We suggest that the malignant potential of OLP may be associated with the expression of Mcl-1, and that downregulation of Mcl-1 may prevent malignant transformation of OLP to oral cancer. PMID:26893789

  1. Oral malignant melanoma: Report of three cases with literature review

    PubMed Central

    Gupta, Shalini; Tandon, Ankita; Ram, Hari; Gupta, O. P.

    2015-01-01

    Primary oral melanoma is known to be an extremely rare and aggressive neoplasm arising from the mucosal epithelium of the oral cavity especially upper jaw (palate or alveolar gingivae). Malignant melanoma that does not originate in the skin is a very rare disease and is considered one of the most deadly of all human neoplasms. Oral malignant melanoma (OMM) represents about 1% of all melanomas and approximately 0.5% of all oral malignancies. OMM has been reported in patients aged 20 to 80 years and has a male predilection. Because most mucosal melanotic lesions are painless in their early stages, so delayed recognition and subsequent treatment result in worst prognosis. Here, we report three cases with significant heterogeneity in morphological features and biologic behavior.

  2. Elucidating drivers of oral epithelial dysplasia formation and malignant transformation to cancer using RNAseq

    PubMed Central

    Conway, Caroline; Graham, Jennifer L.; Chengot, Preetha; Daly, Catherine; Chalkley, Rebecca; Ross, Lisa; Droop, Alastair; Rabbitts, Pamela; Stead, Lucy F.

    2015-01-01

    Oral squamous cell carcinoma (OSCC) is a prevalent cancer with poor prognosis. Most OSCC progresses via a non-malignant stage called dysplasia. Effective treatment of dysplasia prior to potential malignant transformation is an unmet clinical need. To identify markers of early disease, we performed RNA sequencing of 19 matched HPV negative patient trios: normal oral mucosa, dysplasia and associated OSCC. We performed differential gene expression, principal component and correlated gene network analysis using these data. We found differences in the immune cell signatures present at different disease stages and were able to distinguish early events in pathogenesis, such as upregulation of many HOX genes, from later events, such as down-regulation of adherens junctions. We herein highlight novel coding and non-coding candidates for involvement in oral dysplasia development and malignant transformation, and speculate on how our findings may guide further translational research into the treatment of oral dysplasia. PMID:26515596

  3. Marked variation in malignant transformation rates of oral leukoplakia.

    PubMed

    Anderson, Aisling; Ishak, Nurul

    2015-12-01

    Data sourcesSearches were carried out in the Medline, Embase and PubMed databases in July 2014 with a date range, 1960-2013.Study selectionObservational cohort studies (either prospective or retrospective) were included. Studies following identical cohorts, case control studies, clinical trials, interventional studies, laboratory studies, experimental studies, studies with no follow-up data, studies of pre-leukoplakia or snuff-induced lesions were excluded.Data extraction and synthesisThe databases were searched by one reviewer who also screened the studies and evaluated them against the inclusion criteria. Final decision on both inclusion and exclusion of the papers was agreed upon by both authors.ResultsA total of 24 studies were included in this review, involving 12,103 patients. Of the 24 studies included 14 were retrospective. Studies were analysed by subgroup, allowing the authors to identify the rate of malignant transformation as 14.9% with a range of 0.13% to 34%. Only 11 studies gave information on the site of malignant transformation; the most common site was the buccal mucosa. For buccal mucosa the malignant transformation was 3.53%, compared to 24.22% for the tongue. Homogenous oral leukoplakia (OL) was most common, however non-homogenous types showed a higher rate of transformation of 13.1%. There was an increased risk of malignant transformation with age. Most studies demonstrated that there is a higher risk of transformation in the female population.ConclusionsMalignant transformation rate of OL varies from 0.13 to 34% across the 24 studies reviewed here. The authors identified clear risk factors for malignant transformation of oral leukoplakia, including location (tongue), appearance (non-homogenous), increased age and female gender. There was little evidence that surgical intervention had any benefit in reducing the risk of transformation. PMID:26680515

  4. Clinical systemic lupeol administration for canine oral malignant melanoma.

    PubMed

    Yokoe, Inoru; Azuma, Kazuo; Hata, Keishi; Mukaiyama, Toshiyuki; Goto, Takahiro; Tsuka, Takeshi; Imagawa, Tomohiro; Itoh, Norihiko; Murahata, Yusuke; Osaki, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu

    2015-01-01

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

  5. Clinical systemic lupeol administration for canine oral malignant melanoma

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Sento, Shinya; Sasabe, Eri; Yamamoto, Tetsuya

    2016-01-01

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

  7. Reconstruction in oral malignancy: Factors affecting morbidity of various procedures

    PubMed Central

    Chakrabarti, Suvadip; Chakrabarti, Preeti Rihal; Desai, Sanjay M.; Agrawal, Deepak; Mehta, Dharmendra Y.; Pancholi, Mayank

    2015-01-01

    Aims and Objective: (1) To study the age and sex distribution of patient with oral malignancies. (2) To analyze various types of surgery performed. (3) Evaluation of reconstruction and factors affecting complications and its relation to the type of reconstruction. Materials and Methods: Cases of oral malignancies, undergoing surgery for the same in Sri Aurobindo Medical College and PG Institute, Indore from the period from October 1, 2012, to March 31, 2015. Results: Out of analysis of 111 cases of oral malignancy, 31 (27.9%) cases were in the fifth decade of life with male to female ratio 1.9:1. The commonest site of cancer was buccal mucosa. Forty-seven cases (43.2%) were in stage IVa. Diabetes was the most common co-morbidity reported, accounting for 53.9% of cases with reported morbidity. Tobacco chewing was the common entity in personal habits. All the cases underwent neck dissection along with resection of the primary. Hemimandibulectomy was the most preferred form of primary resection accounting for 53.15% (59 cases), followed by wide resection of primary 27% (30 cases). Pectoralis major myocutaneous (PMMC) flap only was the most common reconstruction across the study population. PMMC alone accounted for 38.7% (43 cases). The infection rate was 16.21%. PMMC alone accounted for 5 out of 18 (27.8%) of total infection rate, and 4.5% of the total study population. PMMC + deltopectoral accounted for 5 out of 18 (27.8%) of total infection rate, and 4.5% of the total study population. Conclusion: PMMC is a major workhorse for reconstruction with better functional outcome and acceptance among operated patients. PMID:26981469

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

    NASA Astrophysics Data System (ADS)

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

    2001-10-01

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

  9. Systemic mirnas as potential biomarkers for malignancy.

    PubMed

    Healy, N A; Heneghan, H M; Miller, N; Osborne, C K; Schiff, R; Kerin, M J

    2012-11-15

    MiRNAs are a class of short, endogenous, single-stranded RNA molecules that play a role in the regulation of gene expression. They have been shown to modulate a number of cellular processes including cell differentiation, growth and apoptosis and as a result have been implicated in carcinogenesis. They are detectable in tumour tissue, and altered expression levels have been identified in various cancer types. Of interest, miRNAs have recently been detected and identified to be dysregulated in the circulation of patients with breast cancer. The fact that a minimally invasive test can distinguish the presence or absence of disease illustrates the immense potential these molecules hold as predictive markers. This review serves to identify those systemic miRNAs that are upregulated or downregulated in malignancy and how treatment impacts on their circulating levels. In addition, this review questions the source of these small molecules in the bloodstream and how they may possibly play a role in the future detection of cancer as either prognostic or predictive markers. PMID:22618667

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

    PubMed

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

    2015-03-10

    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

  11. The wonderous chaperones: A highlight on therapeutics of cancer and potentially malignant disorders

    PubMed Central

    Tyagi, Nutan; Tyagi, Rishi

    2015-01-01

    Diverse environmental and physiological factors are known to induce the transcription of a set of genes encoding special protective molecules known as “molecular chaperones” within our cells. Literature abounds in evidence regarding the varied roles; these “guides” can effectively perform in our system. Highly conserved through evolution, from the prokaryotes to the eukaryotes, these make perfect study tools for verifying their role in both the pathogenesis as well as the therapeutics of varied neurodegenerative, autoimmune and potentially malignant disorders and varied cancer states. We present a concise review of this ever dynamic molecule, highlighting the probable role in a potentially malignant disorder, oral lichen planus. PMID:26604499

  12. Magnetic resonance imaging of less common pancreatic malignancies and pancreatic tumors with malignant potential

    PubMed Central

    Franz, D.; Esposito, I.; Kapp, A.-C.; Gaa, J.; Rummeny, E.J.

    2014-01-01

    Pancreatic tumors are an increasingly common finding in abdominal imaging. Various kinds of pathologies of the pancreas are well known, but it often remains difficult to classify the lesions radiologically in respect of type and grade of malignancy. Magnetic resonance imaging (MRI) is the method of choice for the evaluation of pancreatic pathologies due to its superior soft tissue contrast. In this article we present a selection of less common malignant and potentially malignant pancreatic neoplasms with their characteristic appearance on established MRI sequences with and without contrast enhancement. PMID:26937427

  13. Mast Cells and Angiogenesis in Oral Malignant and Premalignant Lesions

    PubMed Central

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

    2008-01-01

    Mast cell contribution to neoangiogenesis during tumorigenesis in oral squamous cell carcinoma is not determined yet. Objectives: To associate numerical mast cell density (MCD) to numerical microvessel density (MVD) during the progression of oral leukoplakia without dysplasia and leukoplakia with dysplasia to squamous cell carcinoma (OSCC). Materials and methods: MVD was analysed immunohistochemically (mouse monoclonal anti-human CD34) in 49 paraffin-embedded specimens, 35 OSCCs, 9 leukoplakias and 5 normal oral tissues. Toluidine blue counterstaining revealed mast cells. MCD and MVD were assessed at the same optical field. Results: MVD increased between: normal oral mucosa, dysplasia (p=0.004), OSCC (p=0.001), leukoplakia and OSCC (p=0.041). MCD increased between: normal oral mucosa, dysplasia (p=0.003), OSCC (p=0.000), leukoplakia and OSCC (p=0.007). MVD was found to depend on MCD (p=0.000) in a percent 28.3% (power curve fit model). Conclusions: Mast cells are attracted at the lesion site and may turn on an angiogenic switch during tumorigenesis in OSCC. PMID:19444318

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2014-09-01

    Fluorescence-guided diagnosis of tumor tissue is in many cases insufficient, because false positive results interfere with the outcome. Improvement through observation of cell metabolism might offer the solution, but needs a detailed understanding of the origin of autofluorescence. With respect to this, spectrally resolved multiphoton fluorescence lifetime imaging was investigated to analyze cell metabolism in metabolic phenotypes of malignant and nonmalignant oral mucosa cells. The time-resolved fluorescence characteristics of NADH were measured in cells of different origins. The fluorescence lifetime of bound and free NADH was calculated from biexponential fitting of the fluorescence intensity decay within different spectral regions. The mean lifetime was increased from nonmalignant oral mucosa cells to different squamous carcinoma cells, where the most aggressive cells showed the longest lifetime. In correlation with reports in the literature, the total amount of NADH seemed to be less for the carcinoma cells and the ratio of free/bound NADH was decreased from nonmalignant to squamous carcinoma cells. Moreover for squamous carcinoma cells a high concentration of bound NADH was found in cytoplasmic organelles (mainly mitochondria). This all together indicates that oxidative phosphorylation and a high redox potential play an important role in the energy metabolism of these cells. PMID:25202900

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

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

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

    SciTech Connect

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

    2008-04-11

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

  18. Molecular and ultrastructural analysis of a multiphasic oral malignant melanoma.

    PubMed

    Zanna, Paola; Lucchese, Alberta; Sevilla, Maria Carmen Turpin; Maida, Immacolata; Fiore, Maria Grazia; Rossi, Roberta; Piscitelli, Domenico; Favia, Gianfranco; Guida, Gabriella

    2011-02-01

    Melanomas of the oral cavity are extremely rare. Their rarity and their independence on exposure to UV radiation make them particularly interesting. The authors analyzed an oral multiphasic melanoma composed by a nodular nonpigmented ulcerated central region, a nodular ulcerated pigmented area, a pigmented nonulcerated region, and an area similar to a dysplastic nevus. They determined the expression of some genes involved in the differentiation and cellular transformation in morphologically different regions of melanoma. All these areas were also analyzed by electron microscopy. The various regions composing the melanoma expressed genes involved in melanogenesis and melanoma progression in a different manner. Electron microscopy observation of ultrathin sections of each region evidenced ultrastructural differences, being the cellular architecture more compromised in the most aggressive parts of the neoplasm. This pilot study identified morphological, molecular, and ultrastructural differences that characterize each region of the multiphasic melanoma. PMID:21265633

  19. Malignant transformation of germinoma 14 years after onset: Favorable efficacy of oral etoposide.

    PubMed

    Fukuoka, Kohei; Yanagisawa, Takaaki; Suzuki, Tomonari; Shirahata, Mitsuaki; Adachi, Jun-ichi; Mishima, Kazuhiko; Fujimaki, Takamitsu; Matsutani, Masao; Nishikawa, Ryo

    2015-06-01

    We report the case of a 19-year-old woman with a highly malignant intracranial germ cell tumor (GCT) that developed 14 years after treatment for neurohypophyseal germinoma. Magnetic resonance imaging (MRI) showed a large neurohypophyseal mass and a synchronous lesion in the pineal region. Plasma ?-fetoprotein was elevated to 3038 ng/mL. Although the tumor shrank and tumor marker levels normalized after chemotherapy and craniospinal irradiation, treatment was switched to oral etoposide for the residual tumor because of adverse events. MRI after oral etoposide introduction showed additional tumor shrinkage for 27 months after the onset of the second tumor. To the best of our knowledge, this is the longest interval between germinoma onset and the development of highly malignant recurrent GCT to be reported in the English-language literature. Oral etoposide prevented regrowth of the GCT, which has a poor prognosis, and decreased the size of the residual tumor. PMID:25712128

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

    PubMed

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

    2014-12-01

    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

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

    PubMed Central

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

    2014-01-01

    Background: Since petrol is combustible and smoking is banned at the petrol pumps, it may be predicted that use of smokeless tobacco is more prevalent among the petrol fillers. Also, smokeless tobacco is a major risk factor for developing oral potentially malignant disorders. The present study was conducted to determine the tobacco use, body mass index (BMI), and potentially malignant disorders among a cohort of petrol fillers and also to evaluate the interaction of tobacco use and BMI with the presence of potentially malignant disorders. Settings and Design: The study was conducted at 45 petrol stations located at Pimpri-Pune, India. A descriptive study design was used. Materials and Method: Four hundred and ten petrol fillers aged 17-64 years participated in the study. General information and tobacco history was obtained by interview. Height and weight were recorded to obtain BMI. Oral examination was conducted to identify the potentially malignant disorders. Statistical analysis: Chi-square test, Z test, and logistic regression were used. The level of significance was fixed at 5%. Results and Conclusions: It was found that 242 (59.02%) used tobacco in different forms. 77.68% were tobacco chewers, and 8.26% were smokers. Leukoplakia was prevalent among 68.47%, oral submucous fibrosis among 27.45%, and 5.08% had erythroplakia. Age (?2 = 11.46, P < 0.05), duration (?2 = 17.46, P < 0.05), and frequency of tobacco chewing (?2 = 14.16, P < 0.05) were significantly associated with potentially malignant disorders. Tobacco chewing was more prevalent as compared to smoking. It can be concluded that the petrol fillers are at a high risk for developing oral potentially malignant disorders. PMID:25422802

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

    PubMed

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

    1987-01-01

    Lectins from the seeds of Jackfruit (Artocarpus integrifolia) and winged bean (Psophocarpus tetragonolobus) were isolated using an immobilized N-acetyl D-galactosamine column and conjugated to type VI horse radish peroxidase. The purified conjugate was used for the study of tissue specificities using diaminobenzidine as the substrate on dewaxed tissue sections of normal, oral leukoplakia, oral submucous fibrosis, verucous carcinoma and squamous cell carcinoma of the oral cavity. In spite of having a common inhibitory sugar, winged bean lectin did not bind to any lectins whereas Jackfruit lectin showed varying degrees of binding towards the above tissues. The difference in the nature and intensity of binding of the Jackfruit lectin suggest the utilizing this lectin in the differential diagnosis of the premalignant and malignant lesions of the oral cavity. PMID:3449613

  3. Integrative metabonomics as potential method for diagnosis of thyroid malignancy.

    PubMed

    Tian, Yuan; Nie, Xiu; Xu, Shan; Li, Yan; Huang, Tao; Tang, Huiru; Wang, Yulan

    2015-01-01

    Thyroid nodules can be classified into benign and malignant tumors. However, distinguishing between these two types of tumors can be challenging in clinics. Since malignant nodules require surgical intervention whereas asymptomatic benign tumors do not, there is an urgent need for new techniques that enable accurate diagnosis of malignant thyroid nodules. Here, we used (1)H NMR spectroscopy coupled with pattern recognition techniques to analyze the metabonomes of thyroid tissues and their extracts from thyroid lesion patients (n?=?53) and their adjacent healthy thyroid tissues (n?=?46). We also measured fatty acid compositions using GC-FID/MS techniques as complementary information. We demonstrate that thyroid lesion tissues can be clearly distinguishable from healthy tissues, and malignant tumors can also be distinguished from the benign tumors based on the metabolic profiles, both with high sensitivity and specificity. In addition, we show that thyroid lesions are accompanied with disturbances of multiple metabolic pathways, including alterations in energy metabolism (glycolysis, lipid and TCA cycle), promotions in protein turnover, nucleotide biosynthesis as well as phosphatidylcholine biosynthesis. These findings provide essential information on the metabolic features of thyroid lesions and demonstrate that metabonomics technology can be potentially useful in the rapid and accurate preoperative diagnosis of malignant thyroid nodules. PMID:26486570

  4. Integrative metabonomics as potential method for diagnosis of thyroid malignancy

    PubMed Central

    Tian, Yuan; Nie, Xiu; Xu, Shan; Li, Yan; Huang, Tao; Tang, Huiru; Wang, Yulan

    2015-01-01

    Thyroid nodules can be classified into benign and malignant tumors. However, distinguishing between these two types of tumors can be challenging in clinics. Since malignant nodules require surgical intervention whereas asymptomatic benign tumors do not, there is an urgent need for new techniques that enable accurate diagnosis of malignant thyroid nodules. Here, we used 1H NMR spectroscopy coupled with pattern recognition techniques to analyze the metabonomes of thyroid tissues and their extracts from thyroid lesion patients (n = 53) and their adjacent healthy thyroid tissues (n = 46). We also measured fatty acid compositions using GC−FID/MS techniques as complementary information. We demonstrate that thyroid lesion tissues can be clearly distinguishable from healthy tissues, and malignant tumors can also be distinguished from the benign tumors based on the metabolic profiles, both with high sensitivity and specificity. In addition, we show that thyroid lesions are accompanied with disturbances of multiple metabolic pathways, including alterations in energy metabolism (glycolysis, lipid and TCA cycle), promotions in protein turnover, nucleotide biosynthesis as well as phosphatidylcholine biosynthesis. These findings provide essential information on the metabolic features of thyroid lesions and demonstrate that metabonomics technology can be potentially useful in the rapid and accurate preoperative diagnosis of malignant thyroid nodules. PMID:26486570

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  7. A rare case of amelanotic malignant melanoma in the oral region: Clinical investigation and immunohistochemical study

    PubMed Central

    OHNISHI, YUICHI; WATANABE, MASAHIRO; FUJII, TOMOKO; SUNADA, NORIKO; YOSHIMOTO, HITOSHI; KUBO, HIROHITO; WATO, MASAHIRO; KAKUDO, KENJI

    2015-01-01

    Amelanotic malignant melanoma (AMM) is rare in the oral region. The present study examined the clinical features of this tumor in an attempt to establish diagnostic criteria. The expression of three melanocytic differentiation markers, HMB-45, S-100 and Melan-A, was also measured in primary oral AMMs in order to determine whether the markers could be used to diagnose primary oral AMMs and to find out which marker was the most sensitive. It may be particularly difficult to correctly diagnose AMM that lacks a radial growth phase without immunohistochemical assistance. In the present study, mixtures of polygonal and spindle cells at different ratios were observed in the tumors with and without a radial growth phase. Immunohistochemistry was used to examine the HMB-45, S-100 and Melan-A expression in the formalin-fixed paraffin-embedded specimens of primary oral AMMs. Comparison of staining intensities (SIs) and labeling indices (LIs) of the markers was also performed. The immunostaining results revealed that the SI of Melan-A was significantly higher than that of S-100 (P=0.0011). HMB-45, S-100 and Melan-A also exhibited high positive rates and LIs in AMMs and, therefore, may be good markers for the immunohistochemical diagnosis of primary oral AMMs. Furthermore, Melan-A may be a more sensitive marker than S-100 and HMB-45, as it has a higher SI. PMID:26788204

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

    SciTech Connect

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

    2005-12-15

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

  9. EZH2 promotes malignant phenotypes and is a predictor of oral cancer development in patients with oral leukoplakia.

    PubMed

    Cao, Wei; Younis, Rania H; Li, Jiang; Chen, Haiyan; Xia, Ronghui; Mao, Li; Chen, Wantao; Ren, Hening

    2011-11-01

    Oral leukoplakia (OL) is the most common premalignancy in the oral cavity. A small proportion of OLs progresses to oral squamous cell carcinoma (OSCC). To assess OSCC risk of OLs, we investigated the role of the transcriptional repressor enhancer of zeste homolog 2 (EZH2) in oral tumorigenesis and its clinical implication as an OSCC risk predictor. Immunohistochemistry was used to measure EZH2 expression in OLs from 76 patients, including 37 who later developed OSCC and 39 who did not. EZH2 expression was associated with clinicopathologic parameters and clinical outcomes. To determine the biological role of EZH2 in OL, EZH2 level was reduced using EZH2 siRNAs in Leuk-1 cells, its impact on cell cycle, anchorage-dependent/independent growth, and invasion was assessed. We observed strong EZH2 expression in 34 (45%), moderate expression in 26 (34%), and weak/no expression in 16 (21%) of the OLs. The higher EZH2 levels were strongly associated with dysplasia (P < 0.001) and OSCC development (P < 0.0001). Multivariate analysis indicated that EZH2 expression was the only independent factor for OSCC development (P < 0.0001). At 5 years after diagnosis, 80% of patients whose OLs expressed strong EZH2 developed OSCC whereas only 24% patients with moderate and none with weak/no EZH2 expression did so (P < 0.0001). In Leuk-1 cells, EZH2 downregulation resulted in G(1) arrest; decreased invasion capability, decreased anchorage-independent growth; downregulation of cyclin D1 and upregulation of p15(INK4B). Our data suggest that EZH2 plays an important role in OL malignant transformation and may be a biomarker in predicting OSCC development in patients with OLs. PMID:21697275

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

    PubMed

    Patil, Pavan Manohar

    2011-09-01

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

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

    PubMed Central

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

    2015-01-01

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

  12. A Potential Therapeutic Strategy for Malignant Mesothelioma with Gene Medicine

    PubMed Central

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

    2013-01-01

    Malignant mesothelioma, closely linked with occupational asbestos exposure, is relatively rare in the frequency, but the patient numbers are going to increase in the next few decades all over the world. The current treatment modalities are not effective in terms of the overall survival and the quality of life. Mesothelioma mainly develops in the thoracic cavity and infrequently metastasizes to extrapleural organs. A local treatment can thereby be beneficial to the patients, and gene therapy with an intrapleural administration of vectors is one of the potential therapeutics. Preclinical studies demonstrated the efficacy of gene medicine for mesothelioma, and clinical trials with adenovirus vectors showed the safety of an intrapleural injection and a possible involvement of antitumor immune responses. Nevertheless, low transduction efficiency remains the main hurdle that hinders further clinical applications. Moreover, rapid generation of antivector antibody also inhibits transgene expressions. In this paper, we review the current status of preclinical and clinical gene therapy for malignant mesothelioma and discuss potential clinical directions of gene medicine in terms of a combinatory use with anticancer agents and with immunotherapy. PMID:23484132

  13. Comparing disciplines: outcomes of non melanoma cutaneous malignant lesions in oral and maxillofacial surgery and dermatology.

    PubMed

    Thavarajah, M; Szamocki, S; Komath, D; Cascarini, L; Heliotis, M

    2015-01-01

    300 cases of non-melanoma cutaneous lesion procedures carried out by the Oral and Maxillofacial Surgery and Dermatology departments in a North West London hospital over a 6 month period between September 2011 and February 2012 were included in a retrospective case control study. The results from each speciality were compared. The mean age of the OMFS group was 75.8 years compared to 69.9 years in the dermatology group. There was no statistically significant difference in gender between the 2 groups. The OMFS group treated a higher proportion of atypical (17%) and malignant (64.9%) cases compared to the dermatology group (11.3% and 50.5% respectively). This could also account for the fact that the OMFS group carried out a higher number of full excisions compared to dermatology. Both groups had a similar number of false positives (a benign lesion initially diagnosed as malignant) and a similar proportion of false negatives (a malignant lesion initially diagnosed as benign). Overall, the results show that both specialities had similar outcomes when managing non-melanoma cutaneous lesions. Both groups adhere to the guidelines set out by the British Association of Dermatologists and the National Institute of Clinical Excellence when managing such lesions. PMID:25468744

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

    PubMed

    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

    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

  15. Origins of heterogeneous ovarian carcinomas. A molecular cytogenetic analysis of histologically benign, low malignant potential, and fully malignant components.

    PubMed Central

    Wolf, N. G.; Abdul-Karim, F. W.; Schork, N. J.; Schwartz, S.

    1996-01-01

    It is unclear whether ovarian carcinomas develop from malignant transformation of benign precursors or whether they arise de novo. Thus, histologically benign or low malignant potential components found in heterogeneous ovarian carcinomas may be remnants of pre-existing lesions that progressed to malignancy or, alternatively, elements that arose independently (de novo). In a third possible interpretation, they represent areas of malignant epithelium that matured. We evaluated clonal relationships of histological components in 10 heterogeneous ovarian carcinomas using fluorescence in situ hybridization and confocal microscopy. Detailed analysis of aneuploidy for chromosomes 8, 12, and 17 on intact paraffin sections revealed that two tumors were aneuploid in all components, two lacked abnormalities in benign-appearing components, and one lacked aneuploidy in both histologically benign and low malignant potential components. Histological appearance was significantly related to aneuploidy (P < 0.05). The distribution of aneuploidy among tumor components strongly supports the tumor progression theory and demonstrates that the de novo hypothesis is highly unlikely (P < 0.001). Results also indicate that benign-appearing components in heterogeneous ovarian carcinomas do not represent maturation of malignant tissue and suggest that some benign tumors that become cancerous may have genetic aberrations that predispose them to malignant transformation. Images Figure 1 Figure 2 PMID:8701990

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

    PubMed

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

    2009-01-01

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

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

    PubMed Central

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

    2015-01-01

    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

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

    PubMed Central

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

    1995-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2008-11-01

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

  20. Tetraspanins CD9 and CD151, epidermal growth factor receptor and cyclooxygenase-2 expression predict malignant progression in oral epithelial dysplasia

    PubMed Central

    Nankivell, P; Williams, H; McConkey, C; Webster, K; High, A; MacLennan, K; Senguven, B; Rabbitts, P; Mehanna, H

    2013-01-01

    Background: Prognostic biomarkers aim to improve on the current inadequate method of histological assessment to identify patients with oral epithelial dysplasia at greatest risk of malignant transformation. We aimed to assess the prognostic ability of six protein biomarkers linked to the epidermal growth factor receptor (EGFR) pathway, including three tetraspanins, in a large multicentre oral dysplasia cohort. Methods: One hundred and forty-eight cases with varying degrees of epithelial dysplasia underwent immunohistochemical assessment for CD9, CD151, CD82, EGFR, Her-2, and COX-2. Scoring was performed independently by two observers. Univariate analyses using both logistic and Cox regression models and a multivariate regression were performed. Results: Malignant progression was significantly greater in those cases with decreased expression of CD9 (P=0.02), and increased expression of CD151 (P=0.02), EGFR (P=0.04), and COX-2 (P=0.003). Histological grade (P=0.0002) and morphology (P=0.03) were also prognostic, whereas smoking and alcohol were not. The optimal combination by backward-variable selection was of histological grade (hazard ratio (HR) 1.64; 95% CI 1.12, 2.40), COX-2 overexpression (HR 1.12; 1.02, 1.24) and CD9 underexpression (HR 0.88; 0.80, 0.97). CD82 and Her-2 demonstrated no prognostic ability. Conclusion: This is the first study of the expression and prognostic potential of the tetraspanins in oral dysplasia. A combination of certain biomarkers with clinical factors appeared to improve the accuracy of determining the risk of malignancy in individuals with oral dysplasia. These findings may also offer potential new therapeutic approaches for this condition. PMID:24201754

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

    PubMed

    Moses, Harold

    2014-10-01

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

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

    PubMed

    Peters, Godefridus J

    2015-11-01

    Fluoropyrimidines form the mainstay in treatment of gastrointestinal malignancies. For decades 5-fluorouracil (5FU), was the major fluoropyrimidine. Currently it is usually given in a combination with leucovorin and oxaliplatin, i.e. FOLFOX, or irinotecan, i.e. FOLFIRI, or all three, i.e. FOLFIRINOX, but gradually it has been replaced by oral fluoropyrimidine prodrug formulations, such as tegafur-uracil and S-1 (both contain ftorafur), and capecitabine (Xeloda®). Novel drugs such as the antivascular endothelial growth factor antibody, bevacizumab, and the anti-epidermal growth factor receptor antibody, cetuximab, are often combined with one of these treatment options. However, when resistance emerged, no alternatives were available. TAS-102, a combination of trifluorothymidine and the thymidine phosphorylase inhibitor TPI in a 1:0.5 ratio, is a novel oral formulation, which is active in 5FU-resistant models, both in vitro and in xenograft models. In addition to inhibition of thymidylate synthase, the major mechanism of action of classical fluoropyrimidines, TAS-102's major mechanism of action is incorporation into DNA, thereby causing DNA damage. TAS-102 also follows an alternative activation pathway via thymidine kinase, and is not a substrate for dihydropyrimidine dehydrogenase. All together this explains the efficacy in 5FU-resistant models. In early clinical studies, the twice-daily schedule (5 days on, 2 days rest) for 2 weeks every 4 weeks, led to a significant disease control rate in various malignancies. This schedule showed consistent activity in two randomized trials on fluoropyrimidine refractory colorectal cancer patients, reflected by an increase of 2-3 months in overall survival in the TAS-102 group compared with placebo. Considering the impressive preclinical potential of various combinations TAS-102 has the promise to become an alternative for 5FU-resistant cancer. PMID:26557901

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

    PubMed Central

    Peters, Godefridus J.

    2015-01-01

    Fluoropyrimidines form the mainstay in treatment of gastrointestinal malignancies. For decades 5-fluorouracil (5FU), was the major fluoropyrimidine. Currently it is usually given in a combination with leucovorin and oxaliplatin, i.e. FOLFOX, or irinotecan, i.e. FOLFIRI, or all three, i.e. FOLFIRINOX, but gradually it has been replaced by oral fluoropyrimidine prodrug formulations, such as tegafur-uracil and S-1 (both contain ftorafur), and capecitabine (Xeloda®). Novel drugs such as the antivascular endothelial growth factor antibody, bevacizumab, and the anti-epidermal growth factor receptor antibody, cetuximab, are often combined with one of these treatment options. However, when resistance emerged, no alternatives were available. TAS-102, a combination of trifluorothymidine and the thymidine phosphorylase inhibitor TPI in a 1:0.5 ratio, is a novel oral formulation, which is active in 5FU-resistant models, both in vitro and in xenograft models. In addition to inhibition of thymidylate synthase, the major mechanism of action of classical fluoropyrimidines, TAS-102’s major mechanism of action is incorporation into DNA, thereby causing DNA damage. TAS-102 also follows an alternative activation pathway via thymidine kinase, and is not a substrate for dihydropyrimidine dehydrogenase. All together this explains the efficacy in 5FU-resistant models. In early clinical studies, the twice-daily schedule (5 days on, 2 days rest) for 2 weeks every 4 weeks, led to a significant disease control rate in various malignancies. This schedule showed consistent activity in two randomized trials on fluoropyrimidine refractory colorectal cancer patients, reflected by an increase of 2–3 months in overall survival in the TAS-102 group compared with placebo. Considering the impressive preclinical potential of various combinations TAS-102 has the promise to become an alternative for 5FU-resistant cancer. PMID:26557901

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  7. Efficacy of Oral Cryotherapy on Oral Mucositis Prevention in Patients with Hematological Malignancies Undergoing Hematopoietic Stem Cell Transplantation: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Zhai, Ruiren; Zhao, Shasha; Luo, Lan; Li, Dandan; Zhao, Xiaoli; Wei, Huaping; Pang, Zhaoxia; Wang, Lili; Liu, Daihong; Wang, Quanshun; Gao, Chunji

    2015-01-01

    Objectives Controversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM) in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT). The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT. Methods PubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs) comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were included. The primary outcomes were the incidence, severity, and duration of OM. The secondary outcomes included length of analgesic use, total parenteral nutrition (TPN) use, and length of hospital stay. Results Seven RCTs involving eight articles analyzing 458 patients were included. Oral cryotherapy significantly decreased the incidence of severe OM (RR = 0.52, 95% CI = 0.27 to 0.99) and OM severity (SMD = -2.07, 95% CI = -3.90 to -0.25). In addition, the duration of TPN use and the length of hospitalization were markedly reduced (SMD = -0.56, 95% CI = -0.92 to -0.19; SMD = -0.44, 95% CI = -0.76 to -0.13; respectively). However, the pooled results were uncertain for the duration of OM and analgesic use (SMD = -0.13, 95% CI = -0.41 to 0.15; SMD = -1.15, 95% CI = -2.57 to 0.27; respectively). Conclusions Oral cryotherapy is a readily applicable and cost-effective prophylaxis for OM in patients undergoing HSCT. PMID:26024220

  8. Current Aspects on Oral Squamous Cell Carcinoma

    PubMed Central

    Markopoulos, Anastasios K

    2012-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  10. Benign and Malignant Proliferative Fibro-osseous and Osseous Lesions of the Oral Cavity of Dogs.

    PubMed

    Soltero-Rivera, M; Engiles, J B; Reiter, A M; Reetz, J; Lewis, J R; Sánchez, M D

    2015-09-01

    Ossifying fibroma (OF) and fibrous dysplasia (FD) are benign, intraosseous, proliferative fibro-osseous lesions (PFOLs) characterized by replacement of normal bone by a fibrous matrix with various degrees of mineralization and ossification. Osteomas are benign tumors composed of mature, well-differentiated bone. Clinical, imaging, and histologic features of 15 initially diagnosed benign PFOLs and osteomas of the canine oral cavity were evaluated. Final diagnoses after reevaluation were as follows: OF (3 cases), FD (4 cases), low-grade osteosarcoma (LG-OSA) (3 cases), and osteoma (5 cases). Histology alone often did not result in a definitive diagnosis for PFOL. OF appeared as a well-circumscribed, radiopaque mass with some degree of bone lysis on imaging. Most lesions of FD showed soft tissue opacity with bone lysis and ill-defined margins. Low-grade OSA appeared as a lytic lesion with a mixed opacity and ill-defined margins. Osteomas were characterized by a mineralized, expansile, well-circumscribed lesion. Although histologic features of PFOLs were typically bland, the lesions diagnosed as LG-OSA had some features of malignancy (eg, bone invasion or a higher mitotic index). Treatment varied widely. Of the 10 dogs with benign PFOL or osteoma with known outcome (10/12), 9 showed either complete response (6/10) or stable disease (3/10) after treatment. Of the 2 dogs with LG-OSA with known outcome, 1 showed complete response after curative intent surgery, but 1 patient had recurrence after partial maxillectomy. Definitive diagnosis of mandibular/maxillary PFOL is challenging via histopathologic examination alone, and accurate diagnosis is best achieved through assimilation of clinical, imaging, and histopathologic features. PMID:25957357

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

    PubMed

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

    2015-12-01

    There have been no recurrences or metastases of clear cell papillary renal cell carcinoma (CCPRCC) in 268 reported cases with follow-up in the English-language literature. We identified all our cases of CCPRCC (1990 to 2013), reviewing all cases that preceded the formal designation of the entity. Immunohistochemical stains were performed on 32 cases during their initial workup. In addition, stains for carbonic anhydrase IX and cytokeratin 7 were performed on 2 cases, one with atypical follow-up and the other with a more compact morphology, although not performed initially. An extended panel with AMACR, CD10, and renal cell carcinoma (RCC) was added to the case with atypical follow-up. Fluorescence in situ hybridization for chromosomes 3p, 7, and 17 was performed on the latter case and on another clinically presumed metastatic tumor. In classic cases, immunohistochemical staining was not performed. Fifty-eight patients (31 women; 27 men) with follow-up data were included in our study; 39 cases were from our consult service. The patients' ages ranged from 36 to 83 years. Thirty-five patients had cystic or partially cystic lesions; 6 tumors were multifocal, 3 of which were bilateral. The majority (53 patients; 91.4%) presented with stage pT1 disease (size range, 0.2 to 8 cm), 2 patients presented with pT2 disease (8.5 and 10.3 cm), 1 patient presented with pT3 disease (6.5 cm sarcomatoid RCC focally extending out of the kidney), and pathologic stage was unavailable in 2 cases. Treatment consisted of 29 partial nephrectomies, 26 radical nephrectomies, 2 cryoablations, and 1 cyst ablation. The resection margins were negative in all but one case, with this case disease free after a 26-month period. Two patients had intraoperative tumor disruption and were disease free at 9 and 34 months. Five patients had synchronous ipsilateral renal cell carcinomas (non-CCPRCC). Mean follow-up time was 21 months (range, 1 to 175 mo), with all but 3 patients having no evidence of disease. One patient was presumed to have contralateral disease on the basis of imaging findings and is alive and well 37 months after multiple partial nephrectomies. Metastatic disease to the lung was clinically presumed in 1 patient in whom a higher-grade lesion may have been missed during sampling of the predominantly cystic pT1b tumor and tissue confirmation of the metastases was not obtained. Another case presented with multiple skeletal and pulmonary metastases 8 months after resection of pT3 sarcomatoid CCPRCC. The patient with the sarcomatoid RCC died of multifocal skeletal and pulmonary metastatic disease 13 months after resection of the renal tumor. Our study, the largest to date with follow-up, along with others, suggests that pure CCPRCC is an indolent tumor and should be renamed "clear cell papillary neoplasm of low malignant potential" to reflect their biology. PMID:26426379

  12. A potential individual cell malignancy indicator: focal length

    NASA Astrophysics Data System (ADS)

    Wang, Weina; Lear, Kevin L.

    2011-03-01

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

  13. Human RGM249-Derived Small RNAs Potentially Regulate Tumor Malignancy

    PubMed Central

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

    2013-01-01

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

  14. Expression of ?B-crystallin and its potential anti-apoptotic role in oral verrucous carcinoma.

    PubMed

    Quan, Hongzhi; Tang, Zhangui; Zhao, Lily; Wang, Yuehong; Liu, Ousheng; Yao, Zhigang; Zuo, Jun

    2012-02-01

    ?B-crystallin, a member of the small heat shock protein family, acts as a molecular chaperone. ?B-crystallin has been found to be overexpressed in a number of cancer tissues, including head and neck cancers. Overexpression of ?B-crystallin in cancer tissue may be related to its anti-apoptotic properties; however, its mechanism of action remains unclear. The aim of this study was to investigate the anti-apoptotic role of ?B-crystallin in oral verrucous carcinoma (OVC). Since oral squamous cell carcinoma (OSCC) is the most common tumor of the oral cavity, we selected OSCC as a control group. Immunohistochemical staining was used to evaluate the expression levels. The results showed that the expression of ?B-crystallin was detected in OVC, OSCC and normal oral mucosa (NM). The expression in OVC was higher compared to that of NM, but lower compared to OSCC, indicating that OVC was less aggressive than OSCC with respect to malignancy potential. Furthermore, we found that in OVC, the increased expression of ?B-crystallin coincided with the decreased expression of activated caspase-3. The results indicated that ?B-crystallin may play an anti-apoptotic role via inhibition of the activation of caspase-3 in OVC. PMID:22740906

  15. A phase II study of cediranib, an oral VEGF inhibitor, in previously untreated patients with metastatic or recurrent malignant melanoma.

    PubMed

    McWhirter, Elaine; Quirt, Ian; Gajewski, Thomas; Pond, Gregory; Wang, Lisa; Hui, June; Oza, Amit

    2016-04-01

    Purpose A two stage multi-institution Phase II study was undertaken by the Princess Margaret Hospital Consortium to evaluate the efficacy and toxicity of oral cediranib, an inhibitor of vascular endothelial growth factor receptors 1 and 2, in patients with previously untreated advanced malignant melanoma. Patients and Methods Between May 2006 and April 2008, 24 patients (median age 65 years) with advanced malignant melanoma were treated with oral cediranib. Cediranib was given on a continuous, oral once daily schedule of 45 mg, on a 28 day cycle. Results Of the 17 patients evaluable for response, there was stable disease in 8 patients, and progressive disease in 9 patients, with no objective responses seen. Only 2 patients had stable disease >/= 6 months, thus the study was terminated at the end of stage 1 accrual. The overall median survival was 9.9 months, and the median time to progression was 3.5 months. The most frequent non-hematologic adverse events were hypertension (78 %), fatigue (69 %), diarrhea (69 %) and anorexia and nausea (each 57 %). Conclusions Although 2 patients had stable disease at 6 months, the short median time to progression and lack of any objective responses indicate that single agent cediranib at this dose and schedule is not sufficiently active to warrant study continuation. PMID:26841902

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

    PubMed

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

    2015-01-01

    Although the great majority of incidentalomas are adrenocortical adenomas, a number of them, depending on the size and radiological characteristics of the lesions, will turn out to be carcinomas. These tumors may present as suspicious on initial evaluation and potentially malignant or malignant on histology. Adrenocortical carcinoma is a rare and aggressive malignancy with evolving diagnostic and therapeutic approaches. Laparoscopic surgery has become the gold standard for surgery of benign adrenal tumors. Despite the extensive experience gained in laparoscopic adrenalectomy, controversy still remains in the management of adrenal tumors with high suspicion or evidence of malignancy. The aim of this review is to update the existing information regarding the diagnostic approach and surgical management of suspicious and potentially malignant primary adrenal tumors.The interpretation of radiologic characteristics is a cornerstone in pre-operative assessment of large adrenal masses, since open surgery remains the preferred procedure when malignancy is suspected in large tumors with possible local invasion. Despite the improvement of imaging techniques, they lack sufficient accuracy to exclude primary malignancy in tumors from 4 cm to 10 cm in size. An initial laparoscopic approach can be used in this group of patients, but early conversion to open technique is mandatory if curative resection cannot be performed. Adrenal tumors >10 cm of malignant potential should be treated by the open approach from the start. Solitary adrenal metastasis from another primary malignancy is usually amenable to laparoscopic surgery. Patients with suspected adrenal cancer should be referred to tertiary centers that perform laparoscopic and open adrenal surgery with minimal morbidity and mortality. PMID:25885103

  17. Oral squamous cell carcinoma of the maxilla, a second malignancy after a right ethmoido-maxillary chondrosarcoma.

    PubMed

    Suciu, Mircea; Morariu, Silviu Horia; Ormeni?an, Alina; Grigora?, Radu Ionu?; Bostan, Radu Horia; Mocanu, Simona; Vartolomei, Mihai Dorin; Cotoi, Ovidiu Simion

    2014-01-01

    Squamous cell carcinoma is defined as an invasive epithelial neoplasm, with variable degrees of squamous differentiation, with or without keratinization. It is origins stand at the level of the keratinized stratified squamous epithelium (skin) or non-keratinized (oral mucosa, esophageal mucosa, uterine exocervical mucosa), but it can also be found in squamous metaplasia areas (uterine endocervix or trachea-bronchial tree). This report presents the case of an oral squamous cell carcinoma as a second malignancy in the same anatomical territory, in a patient with prior treatment for chondrosarcoma, both surgical and radiotherapy. The tumor had appeared 5-6 months prior and had undergone a relatively rapid growth, this being the patient's main motive for addressing the doctors. The tumor was greyish, with imprecisely demarcated margins, of firm consistency, bleeding and with local necrotic deposits. The tumor extended from the incisive region to the maxillary tuberosity, towards the cheek mucosa and the soft palate. After a large excision, the histopathological diagnosis was infiltrative keratinizing squamous cell carcinoma, with moderate differentiation, with origins in the oral mucosa, infiltrating the whole of the maxilla and the maxillary sinus mucosa. Approximately three months after the surgery, a new tumor appeared in the oral cavity, on superior and inferior mucosa of the right cheek, extending towards the right buccal commissure, implying a relapse of the primary tumor. Postoperative oncological therapy included standard chemotherapy, which resulted in favorable postoperative evolution. This case is interesting by the association, of two metachronous malignant tumors, of different histological origin: a chondrosarcoma and a squamous cell carcinoma, at an interval of 25 years. PMID:25607415

  18. DOK, a cell line established from human dysplastic oral mucosa, shows a partially transformed non-malignant phenotype.

    PubMed

    Chang, S E; Foster, S; Betts, D; Marnock, W E

    1992-12-01

    There are many reports of cell lines being established from human oral squamous-cell carcinomas but apparently none of cell lines from dysplastic or "pre-malignant" oral mucosa. We describe here the isolation and characterization of a cell line, DOK (dysplastic oral keratinocyte), from a piece of dorsal tongue showing epithelial dysplasia. The tissue was obtained from a 57-year-old man who was a heavy smoker prior to the appearance of a white patch on his tongue. Eleven years later a squamous-cell carcinoma developed at the site and was excised. Subsequently the remaining dysplasia was removed, and it was from a piece of this that the primary cell cultures which eventually gave rise to DOK were initiated. The DOK line has been single-cell cloned and is apparently immortal. It grows in the absence of 3T3 feeder cells, is anchorage-dependent for growth and is non-tumorigenic in nude mice. The keratin profile of the cells shows a striking similarity to that of the original tongue dysplasia. The karyotype of DOK is aneuploid and complex. By PCR and oligonucleotide hybridization on dot blots, codons 12, 13 and 61 of Ha-ras, Ki-ras and N-ras in DNA extracted from DOK cells were shown to be normal. Immunohistochemistry showed no abnormal, i.e., elevated expression of the onco-suppressor protein p53. Because of its origin and partially transformed phenotype, DOK presents an opportunity to study whether specific carcinogens associated with tobacco and areca nut can cause malignant transformation of oral keratinocytes in vitro. PMID:1459732

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

    PubMed Central

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

    2013-01-01

    Objective: To evaluate the degree of expression of cyclin-D1, p27 and p63 in mild, moderate and severe dysplasia using immunohistochemical evaluation in order to illustrate their prognostic value and attempt to propose a molecular grading system for oral epithelial dysplasia. Materials and Methods: The analysis included thirty cases of mild, moderate and severe dysplasia from Department of Oral and Maxillofacial Pathology, Saveetha Dental College, Chennai after a critical review of the Hematoxylin and Eosin (H and E) stained sections. They were subjected to immunohistochemical evaluation using the markers cyclin-D1, p27 and p63. The assessment of the expression based on staining intensity and distribution of immunohistochemical staining of the various markers was analyzed followed by statistical analysis. Results: A highly significant increase in the expression of cyclin-D1 (P < 0.000) and p63 (P < 0.001) and a moderately significant decrease in the expression of p27 (P < 0.012) with the increasing severity of dysplasia was observed in our study. Conclusions: The result of our research affirms the fact that the increase in the expression of markers of cell cycle regulators such as cyclin D1, decrease in the expression of cell cycle inhibitors like p27 and increased expression of p63 in parallel with the increasing severity of dysplasia, emphasizes the use of immunohistochemical markers cyclin D1, p27 and p63 as prognostic markers for better understanding the behaviour of these potentially malignant disorders aiming towards proposing a molecular grading system for oral epithelial dysplasia to enable timely management prior to their possible malignant transformation. PMID:24082731

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

    PubMed Central

    2013-01-01

    Background Proper expression and functioning of transcription factors (TFs) are essential for regulation of different traits and thus could be crucial for the development of complex diseases. Subjects with Down syndrome (DS) have a higher incidence of acute lymphoblastic leukemia (ALL) while solid tumors, like breast cancer (BC) and oral cancer (OC), show rare incidences. Triplication of the human chromosome 21 in DS is associated with altered genetic dosage of different TFs. V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) and Single Minded 2 (SIM2) are two such TFs that regulate several downstream genes involved in developmental and neurological pathways. Here we studied functional genetic polymorphisms (fSNP) in ETS2 and SIM2 encoding genes in a group of patients and control subjects to better understand association of these variants with DS phenotypes. Methods We employed an in silico approach to identify potential target pathways of ETS2 and SIM2. fSNPs in genes encoding for these two TFs were identified using available databases. Selected sites were genotyped in individuals with DS, their parents, ALL, BC, OC as well as ethnically matched control individuals. We further analyzed these data by population-based statistical methods. Results Allelic/genotypic association analysis showed significant (P?malignant groups, which affects different downstream biological pathways. Thus, altered expression of SIM2 and ETS2 could be one of the reasons for variable occurrence of different malignant conditions in DS. PMID:23343470

  1. Prophylaxis of mucosal toxicity by oral propantheline and cryotherapy in children with malignancies undergoing myeloablative chemo-radiotherapy.

    PubMed

    Sato, Atsushi; Saisho-Hattori, Takako; Koizumi, Yoshitsugu; Minegishi, Masayoshi; Iinuma, Kazuie; Imaizumi, Masue

    2006-12-01

    Mucosal toxicity is an incapacitating complication of intensive chemo-radiotherapy for children with malignant disorders, and is physically and psychologically distressful. It is therefore important to minimize mucosal toxicity in those patients. In this report, the effects of the combined prophylaxis of oral cooling (cryotherapy) and administration of propantheline, an anticholinergic drug, were studied in patients (aged 2-16 year) with acute leukemias or solid tumors, who underwent myeloablative chemo-radiotherapy and autologous peripheral blood stem cell rescue from 1993 to 1997. Patients were pretreated with the combined prophylaxis (n = 12) or single prophylaxis (n = 5), or left untreated (n = 7). The combined prophylaxis significantly reduced the severe mucositis (combined, 8.3%; single, 20.0%; and untreated, 42.9%) and severe diarrhea (combined, 16.7%; single, 60.0%; and untreated, 57.1%). Moreover, the combined prophylaxis tended to shorten the periods of febrile episodes defined as temperature > 38 degrees C (combined, 3.8 days; single, 4.6 days; and untreated, 5.6 days). Therefore, the combination of propantheline and oral cryotherapy may be feasible and effective for reduction of mucosal toxicity in patients with malignancy who undergo high-dose chemotherapy. PMID:17146197

  2. Mucoadhesive oral films: The potential for unmet needs.

    PubMed

    Silva, Branca M A; Borges, Ana Filipa; Silva, Cláudia; Coelho, Jorge F J; Simões, Sérgio

    2015-10-15

    Oral drug delivery is the most common route of drug administration. Nevertheless, there are some important limitations that reinforce the need for developing new drug delivery systems. Mucoadhesive oral films (MOF) are promising dosage forms that adhere to the oral mucosa and deliver the drug through it, which present several advantages. These include: bypassing the hepatic first pass effect, fast onset of action, ease of transportation and handling. The use of such dosage form is beneficial for drugs that have poor oral bioavailability and also for drugs that need to be rapidly absorbed. In spite of the known benefits, the number of marketed MOF is still quite small. This review explores the products under development and corresponding clinical trials in respect to their status, therapeutic indication, companies involved and technologies. In this way, it was possible to identify the preferred therapeutic indications, new research and market trends as well as future prospects of MOF. Moreover, it is reasonable to expect an increase in the number of products on the market due to their great potential to satisfy unmet medical needs. PMID:26315122

  3. Phase I Study of Oral Rigosertib (ON 01910.Na), a Dual Inhibitor of the PI3K and Plk1 Pathways, in Adult Patients with Advanced Solid Malignancies

    PubMed Central

    Bowles, Daniel W.; Diamond, Jennifer R.; Lam, Elaine T.; Weekes, Colin D.; Astling, David P.; Anderson, Ryan T.; Leong, Stephen; Gore, Lia; Varella-Garcia, Marileila; Vogler, Brian W.; Keysar, Stephen B.; Freas, Elizabeth; Aisner, Dara L.; Ren, Chen; Tan, Aik-Chook; Wilhelm, Francois; Maniar, Manoj; Eckhardt, S. Gail; Messersmith, Wells A.; Jimeno, Antonio

    2014-01-01

    Purpose To determine the pharmacokinetics (PK), maximum tolerated dose (MTD), safety, and antitumor activity of an oral formulation of rigosertib, a dual phosphoinositide 3-kinase (PI3K) and polo-like kinase 1 (Plk1) pathway inhibitor, in patients with advanced solid malignancies. Experimental Design Patients with advanced solid malignancies received rigosertib twice daily continuously in 21-day cycles. Doses were escalated until intolerable grade ≥ 2 toxicities, at which point the previous dose level was expanded to define the MTD. All patients were assessed for safety, PK, and response. Urinary PK were performed at the MTD. Archival tumors were assessed for potential molecular biomarkers with multiplex mutation testing. A subset of squamous cell carcinomas (SCC) underwent exome sequencing. Results Forty-eight patients received a median of 2 cycles of therapy at 5 dose levels. Rigosertib exposure increased with escalating doses. Dose-limiting toxicities were hematuria and dysuria. The most common grade ≥2 drug-related toxicities involved urothelial irritation. The MTD is 560 mg twice daily. Activity was seen in head and neck SCCs (1 complete response, 1 partial response) and stable disease for ≥ 12 weeks was observed in 8 additional patients. Tumors experiencing ≥partial response had PI3K pathway activation, inactivated p53, and unique variants in ROBO3 and FAT1, two genes interacting with the Wnt/β-catenin pathway. Conclusions The recommended phase II dose of oral rigosertib is 560 mg twice daily given continuously. Urinary toxicity is the dose-limiting and most common toxicity. Alterations in PI3K, p53, and Wnt/β-catenin pathway signaling should be investigated as potential biomarkers of response in future trials. PMID:24493827

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

    PubMed

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

    2014-04-01

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

  5. Malignant epignathus.

    PubMed

    Rayudu, Harijan Hanumantha; Reddy, Kilashnath; Lakshmi, Kasa; Varma, Santhosh

    2011-07-01

    Report of a neonate with a huge mass protruding from the oral cavity. The mass has originated from the base of the tongue. Successful excision and histopathological examination revealed it to be a malignant epignathus. PMID:21897571

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

    PubMed Central

    Bodhade, Ashish S.; Dive, Alka M.

    2013-01-01

    The word chemoprevention includes prevention of initiation, promotion, and progression of carcinogenesis to cancer. This article is an attempt to review the dietary chemopreventive agents and their mode of action in chemoprevention of oral premalignant lesions and oral cancer using a systematic approach. Selected chemoprevention trials are discussed with a focus on strategies of trial design and clinical outcome. Future in the field of chemoprevention will be more promising than the recently available therapeutic alternatives. PMID:24883036

  7. γ-Synuclein Expression Is a Malignant Index in Oral Squamous Cell Carcinoma.

    PubMed

    Cheng, J C; Chiang, M T; Lee, C H; Liu, S Y; Chiu, K C; Chou, Y T; Huang, R Y; Huang, S M; Shieh, Y S

    2016-04-01

    Dysregulation of γ-synuclein (SNCG) has been reported in many cancers; however, its role in cancer development is still controversial. Here, we examined the potential involvement of DNA methylation in regulating SNCG and its role in oral squamous cell carcinoma (OSCC). We used 8 OSCC cell lines to investigate SNCG methylation and expression. SNCG methylation was examination by methylation-specific polymerase chain reaction and bisulfate sequencing. Cells showing a high degree of SNCG methylation were treated with 5-aza (methylation inhibitor), and changes in their methylation and expression profiles were analyzed. Functional effects of SNCG in OSCC were examined by its overexpression and knockdown. Additionally, methylation and expression of SNCG in OSCC tissues were investigated and correlated with clinicopathologic features. All OSCC cells showed detectable SNCG expression at the mRNA and protein levels. Methylation-specific polymerase chain reaction and bisulfate sequencing revealed high SNCG expression in SCC25 cells with the unmethylated allele, and their 15 CpG islands were unmethylated. The methylated allele was detected only in OEC-M1 cells exhibiting low SNCG expression, and their CpG islands were partially methylated. 5-aza treatment in OEC-M1 cells attenuated methylation and restored SNCG expression. SNCG overexpression increased colony forming, migration, and invasion abilities in OEC-M1 cells. Silencing SNCG in SCC25 cells suppressed these behaviors. All 25 tumor-adjacent normal tissues were negative for SNCG immunostaining. SNCG upregulation was frequently observed in dysplastic and OSCC tissues. Positive SNCG expression was found in 45% (37 of 82) OSCC tissues. Positive SNCG expression in OSCC significantly correlated with cancer staging and lymph node metastasis. However, SNCG methylation did not correlate with its expression and clinicopathologic variables in OSCC tissues. DNA methylation may participate in regulating SNCG expression in some OSCC cells. SNCG upregulation could be involved in OSCC progression. PMID:26661712

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

    PubMed Central

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

    2014-01-01

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

  9. Characteristics of ovarian tumors of low malignant potential in BRCA mutation carriers: A case series.

    PubMed

    Matsuo, Koji; Tierney, Katherine E; Schneider, Diane M; Mhawech-Fauceglia, Paulette; Roman, Lynda D; Gershenson, David M

    2015-08-01

    •Tumor characteristics of 5 cases of ovarian tumor of low malignant potential (LMP) with BRCA mutation were examined.•Young age, BRCA1 mutation, and presence of invasive implants may be characteristics of BRCA carriers with ovarian LMP. PMID:26425718

  10. Saliva proteome profiling reveals potential salivary biomarkers for detection of oral cavity squamous cell carcinoma.

    PubMed

    Wu, Chih-Ching; Chu, Hao-Wei; Hsu, Chia-Wei; Chang, Kai-Ping; Liu, Hao-Ping

    2015-10-01

    Oral cavity squamous cell carcinoma (OSCC), which is frequently associated with poor prognosis and mortality, is a leading cause of cancer-related death worldwide. Discovery of body fluid accessible biomarkers is needed to improve OSCC screening. To this end, we profiled proteomes of saliva from the healthy volunteers, the individuals with oral potentially malignant disorders (OPMD), and the OSCC patients by means of SDS-PAGE coupled with LC-MS/MS. In the control, the OPMD, and the OSCC groups, 958, 845, and 1030 salivary proteins were detected, respectively. With spectral counting-based label-free quantification, 22 overexpressed salivary proteins were identified in the OSCC group compared with the healthy controls and the OPMD individuals. Among them, resistin (RETN) was subjected to further validation with an independent cohort using ELISA. The data confirmed that the salivary RETN levels in the OSCC patients were significantly higher than that in the healthy or in the OPMD group. Moreover, the elevated levels of salivary RETN were highly correlated with late-stage primary tumors, advanced overall stage, and lymph-node metastasis. Our results not only reveal that profiling of saliva proteome is feasible for discovery of OSCC biomarkers, but also identify RETN as a potential salivary biomarker for OSCC detection. PMID:26205615

  11. Lesions of uncertain malignant potential in the breast (B3): what do we know?

    PubMed

    Purushothaman, H N; Lekanidi, K; Shousha, S; Wilson, R

    2016-02-01

    Breast lesions classified as of uncertain malignant potential (B3) on biopsy form a diverse group of abnormalities, which pose a diagnostic and management challenge. In this paper, we discuss the imaging and pathology features as well as the management of the most controversial B3 lesions, consisting of papillary lesions, complex sclerosing lesions/radial scars, lobular intraepithelial neoplasia, and atypical epithelial proliferation of ductal type. As there is an association with malignancy at the time of diagnosis, as well as an increase in the risk of subsequent development of cancer, a multidisciplinary discussion is almost always required to tailor treatment. PMID:26607917

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

    PubMed

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

    2016-01-12

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

  13. Malignant transformation of proliferative verrucous leukoplakia to oral squamous cell carcinoma: a series of 55 cases.

    PubMed

    Bagan, Jose V; Jiménez-Soriano, Yolanda; Diaz-Fernandez, Jose M; Murillo-Cortés, Judith; Sanchis-Bielsa, José M; Poveda-Roda, Rafael; Bagan, Leticia

    2011-08-01

    In this study, we compared clinical differences between patients with proliferative verrucous leukoplakia (PVL) who did and did not develop oral cancer. This was a retrospective study of 55 PVL cases. All patients were followed for at least 1year, with a mean follow-up of 7.53 (SD=4.18) years. The mean age of the patients was 61.69 (SD=11.76) years. There were 36 (65.5%) females and 19 (34.5%) males. Group 1 included the 28 PVL patients who did not develop oral squamous cell carcinoma (OSCC) during the period. Group 2 included the 27 PVL patients who developed at least one OSCC during the period. The latter group was subdivided into patients with PVL who developed one (Subgroup 2a; n=16) or more than one (Subgroup 2b; n=11) OSCC during follow-up. There was no statistical difference in age or oral location of the PVL between Groups 1 and 2. Females had a greater tendency to develop cancer than males (58.3% vs. 31.6%). In Group 2, only six (22.2%) were smokers. There was no difference between Subgroups 2a and b in terms of age, gender, and oral location of the PVL. Subgroup 2b included fewer smokers, had higher gingival involvement rate, and lower frequency of PVL on the tongue. The PVL patients who develop oral cancers were more commonly female and non-smokers. Those patients who developed more than one OSCC were most likely to develop lesions of the gingiva. PMID:21683646

  14. The novel herbal cocktail MA128 suppresses tumor growth and the metastatic potential of highly malignant tumor cells.

    PubMed

    Kim, Aeyung; Im, Minju; Yim, Nam-Hiu; Hwang, Youn-Hwan; Yang, Hye Jin; Ma, Jin Yeul

    2015-08-01

    MA128, a novel herbal medicine, was previously identified and its effectiveness in the treatment of asthma and atopic dermatitis (AD) was demonstrated. In particular, post-inflammatory hyperpigmentation (PIH) in AD mice was improved by treatment with MA128. In addition, MA128 exhibited anti-melanogenic activity by inhibiting tyrosinase activity via the p38 MAPK and protein kinase A signaling pathways in B16F10 cells. In the present study, we examined whether oral administration of MA128 suppressed the in vivo tumor growth of HT1080 cells in athymic nude mice. The results showed that the daily oral administration of 75 and 150 mg/kg MA128 suppressed the tumorigenic growth of HT1080 cells efficiently. Since metastasis is a major cause of cancer-associated mortality and the greatest challenge during cancer treatment, we investigated the effect of non-toxic concentrations of MA128 on the metastatic potential of HT1080 cells. MA128 inhibited anchorage-independent colony formation, migration and invasion. Matrix metalloproteinase-9 (MMP-9) activity under resting and PMA-stimulated conditions was decreased in a dose-dependent manner by MA128 in HT1080 cells. In addition, the daily oral administration of MA128 at doses of 75 and 150 mg/kg efficiently blocked the lung metastasis of B16F10 cells that had been injected into the tail veins of C57BL/6 mice. In particular, none of the mice treated with MA128 exhibited systemic toxicity, such as body weight loss or liver and kidney dysfunction. MA128 also inhibited tumor?induced angiogenesis. Taken together, the results suggest that MA128 is a potential therapeutic agent and a safe herbal medicine for controlling malignant and metastatic cancer. PMID:26035620

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

    NASA Astrophysics Data System (ADS)

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

    2006-02-01

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

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

    PubMed Central

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

    2014-01-01

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

  17. Human salivary proteome--a resource of potential biomarkers for oral cancer.

    PubMed

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

    2015-09-01

    Proteins present in human saliva offer an immense potential for clinical applications. However, exploring salivary proteome is technically challenged due to the presence of amylase and albumin in high abundance. In this study, we used four workflows to analyze human saliva from healthy individuals which involved depletion of abundant proteins using affinity-based separation methods followed by protein or peptide fractionation and high resolution mass spectrometry analysis. We identified a total of 1256 human salivary proteins, 292 of them being reported for the first time. All identifications were verified for any shared proteins/peptides from the salivary microbiome that may conflict with the human protein identifications. On integration of our results with the analyses reported earlier, we arrived at an updated human salivary proteome containing 3449 proteins, 808 of them have been reported as differentially expressed proteins in oral cancer tissues. The secretory nature of 598 of the 808 proteins has also been supported on the basis of the presence of signal sequence, transmembrane domain or association with exosomes. From this subset, we provide a priority list of 139 proteins along with their proteotypic peptides, which may serve as a reference for targeted investigations as secretory markers for clinical applications in oral malignancies. This article is part of a Special Issue entitled: Proteomics in India. PMID:26073025

  18. Essentials of oral cancer

    PubMed Central

    Rivera, César

    2015-01-01

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

  19. The Potential Malignancy of a Solitary Fibrous Tumour of the Lung

    PubMed Central

    Shukla, Rajeev; Patrini, Davide; Borg, Elaine; Lawrence, David; Hayward, Martin; Panagiotopoulos, Nikolaos

    2015-01-01

    Solitary fibrous tumours (SFTs) are rare neoplasms that in the majority of cases are benign. We present the case of a 52-year-old male, with a 23-year history of a slow growing pleural mass, presenting to our department with worsening dyspnoea and localised chest discomfort. The purpose of this case report is to highlight the potential malignancy of a solitary fibrous tumour of the lung along with the key features in diagnosis and management.

  20. Stromal Tumor of Uncertain Malignant Potential (STUMP) With PSA >500 ng/ml: A Case Report

    PubMed Central

    Johnson, Michael H.; Carter, H. Ballentine

    2015-01-01

    Stromal tumors of uncertain malignant potential (STUMP) are rare diagnoses in the evaluation of elevated PSA. The management of STUMP in the setting of an elevated PSA is challenging, as STUMP may have a benign clinical course. In this report, we describe a patient who was found to have a PSA >500 ng/ml and a large STUMP. We review the critical findings and review the relevant literature on diagnosis and management strategies for patients with STUMP. PMID:26793543

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-02-01

    Targeted kinase inhibitors and camptothecins have shown preclinical and clinical activity in several cancers. This trial evaluated the maximum tolerated dose (MTD) and dose-limiting toxicities of sorafenib and topotecan administered orally in pediatric patients with relapsed solid tumors. Sorafenib was administered twice daily and topotecan once daily on days 1-5 and 8-12 of each 28-day course. The study utilized a standard 3 + 3 dose escalation design. Three dose levels (DL) were evaluated: (1) sorafenib 150 mg/m(2) and topotecan 1 mg/m(2) ; (2) sorafenib 150 mg/m(2) and topotecan 1.4 mg/m(2) ; and (3) sorafenib 200 mg/m(2) and topotecan 1.4 mg/m(2) . Pharmacokinetics were ascertained and treatment response assessed. Thirteen patients were enrolled. DL2 was the determined MTD. Grade 4 thrombocytopenia delaying therapy for >7 days was observed in one of six patients on DL2, and grade 4 neutropenia that delayed therapy in two of three patients on DL3. A patient with preexisting cardiac failure controlled with medication developed a transient drop in the left ventricular ejection fraction that improved when sorafenib was withheld. Sorafenib exposure with or without topotecan was comparable, and the concentration-time profiles for topotecan alone and in combination with sorafenib were similar. One objective response was noted in a patient with fibromatosis. We determined MTD to be sorafenib 150 mg/m(2) twice daily orally on days 1-28 combined with topotecan 1.4 mg/m(2) once daily on days 1-5 and 8-12. While these doses are 1 DL below the MTD of the agents individually, pharmacokinetic studies suggested adequate drug exposure without drug interactions. The combination had limited activity in the population studied. PMID:26714427

  3. The Potential Role of Oral Fluid in Antidoping Testing

    PubMed Central

    Anizan, Sebastien; Huestis, Marilyn A.

    2015-01-01

    BACKGROUND Currently, urine and blood are the only matrices authorized for antidoping testing by the World Anti-Doping Agency (WADA). Although the usefulness of urine and blood is proven, issues remain for monitoring some drug classes and for drugs prohibited only in competition. The alternative matrix oral fluid (OF) may offer solutions to some of these issues. OF collection is easy, noninvasive, and sex neutral and is directly observed, limiting potential adulteration, a major problem for urine testing. OF is used to monitor drug intake in workplace, clinical toxicology, criminal justice, and driving under the influence of drugs programs and potentially could complement urine and blood for antidoping testing in sports. CONTENT This review outlines the present state of knowledge and the advantages and limitations of OF testing for each of the WADA drug classes and the research needed to advance OF testing as a viable alternative for antidoping testing. SUMMARY Doping agents are either prohibited at all times or prohibited in competition only. Few OF data from controlled drug administration studies are available for substances banned at all times, whereas for some agents prohibited only in competition, sufficient data may be available to suggest appropriate analytes and cutoffs (analytical threshold concentrations) to identify recent drug use. Additional research is needed to characterize the disposition of many banned substances into OF; OF collection methods and doping agent stability in OF also require investigation to allow the accurate interpretation of OF tests for antidoping monitoring. PMID:24153253

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

    PubMed Central

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

    2014-01-01

    Mast cells (MCs) expressing serine proteases; tryptase and chymase, are associated with fibrosis in various diseases. However, little is known about their involvement in oral submucous fibrosis (OSF). Our goal was to evaluate the role of MC tryptase and chymase in the pathogenesis of OSF and its malignant transformation. Immunohistochemical expression of MC tryptase and chymase was evaluated in 20 cases of OSF, 10 cases of oral squamous cell carcinoma (OSCC) and 10 cases of healthy controls. Subepithelial zone of Stage 1 and 2 while deep zone of Stage 3 and 4 OSF demonstrated increased tryptase positive MCs. OSCC revealed a proportionate increase in tryptase and chymase positive MCs irrespective of areas of distribution. An altered balance in the subepithelial and deep distribution of tryptase and chymase positive MCs play an important role in the pathogenesis of OSF and its malignant transformation. PMID:24874976

  5. Oral microbiota and cancer

    PubMed Central

    Meurman, Jukka H.

    2010-01-01

    Inflammation caused by infections may be the most important preventable cause of cancer in general. However, in the oral cavity the role of microbiota in carcinogenesis is not known. Microbial populations on mouth mucosa differ between healthy and malignant sites and certain oral bacterial species have been linked with malignancies but the evidence is still weak in this respect. Nevertheless, oral microorganisms inevitably up-regulate cytokines and other inflammatory mediators that affect the complex metabolic pathways and may thus be involved in carcinogenesis. Poor oral health associates statistically with prevalence of many types of cancer, such as pancreatic and gastrointestinal cancer. Furthermore, several oral micro-organisms are capable of converting alcohol to carcinogenic acetaldehyde which also may partly explain the known association between heavy drinking, smoking, poor oral health and the prevalence of oral and upper gastrointestinal cancer. A different problem is the cancer treatment-caused alterations in oral microbiota which may lead to the emergence of potential pathogens and subsequent other systemic health problems to the patients. Hence clinical guidelines and recommendations have been presented to control oral microbiota in patients with malignant disease, but also in this area the scientific evidence is weak. More controlled studies are needed for further conclusion. PMID:21523227

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

    PubMed Central

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

    2015-01-01

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

  7. The human oral metaproteome reveals potential biomarkers for caries disease.

    PubMed

    Belda-Ferre, Pedro; Williamson, James; Simón-Soro, Áurea; Artacho, Alejandro; Jensen, Ole N; Mira, Alex

    2015-10-01

    Tooth decay is considered the most prevalent human disease worldwide. We present the first metaproteomic study of the oral biofilm, using different mass spectrometry approaches that have allowed us to quantify individual peptides in healthy and caries-bearing individuals. A total of 7771 bacterial and 853 human proteins were identified in 17 individuals, which provide the first available protein repertoire of human dental plaque. Actinomyces and Coryneybacterium represent a large proportion of the protein activity followed by Rothia and Streptococcus. Those four genera account for 60-90% of total diversity. Healthy individuals appeared to have significantly higher amounts of L-lactate dehydrogenase and the arginine deiminase system, both implicated in pH buffering. Other proteins found to be at significantly higher levels in healthy individuals were involved in exopolysaccharide synthesis, iron metabolism and immune response. We applied multivariate analysis in order to find the minimum set of proteins that better allows discrimination of healthy and caries-affected dental plaque samples, detecting seven bacterial and five human protein functions that allow determining the health status of the studied individuals with an estimated specificity and sensitivity over 96%. We propose that future validation of these potential biomarkers in larger sample size studies may serve to develop diagnostic tests of caries risk that could be used in tooth decay prevention. PMID:26272225

  8. Malignant potential of juvenile polyposis coli. Report of a case and review of the literature.

    PubMed

    Longo, W E; Touloukian, R J; West, A B; Ballantyne, G H

    1990-11-01

    Juvenile polyps of the colon and rectum traditionally have been viewed as being benign inflammatory or harmartomatous lesions without potential for malignant change. The authors report a case of adenocarcinoma developing in a patient with sporadic juvenile polyposis. Juvenile polyposis was diagnosed in the patient at age 4 years. He underwent subtotal colectomy at age 6 years. At age 12, he underwent a proctectomy and a Swenson pull-through because of adenomatous changes in the rectal stump. At age 19 surveillance endoscopy revealed invasive cancer in a juvenile polyp. PMID:2226089

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

    PubMed Central

    Dall’Asta, Andrea; Gizzo, Salvatore; Musarò, Andrea; Quaranta³, Michela; Noventa, Marco; Migliavacca, Costanza; Sozzi, Giulio; Monica, Michela; Mautone, Daniele; Berretta, Roberto

    2014-01-01

    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

  10. Novel oral drug formulations. Their potential in modulating adverse effects.

    PubMed

    Florence, A T; Jani, P U

    1994-03-01

    The rationale for specialised oral formulations of drugs include prolongation of effect for increased patient convenience and reduction of adverse effects through lowered peak plasma concentrations. Local and systemic adverse effects due to high concentrations of drug can be minimised by the use of controlled release delivery systems. Local effects in the gastrointestinal (GI) tract from the release of irritant drug molecules can also be reduced, but the gastric damage caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is only partially relieved by formulation approaches because of the involvement of systemic factors in the aetiology of GI adverse events. The advantages for each drug class must be examined. Newer dosage forms include: (i) osmotic pumps and zero order kinetics systems to control the release rate of the drug; (ii) bioadhesive systems and gastric retention devices to control GI transit; (iii) bioerodible hydrogels; (iv) molecular carrier systems (e.g. cyclodextrin-encapsulated drugs) to modulate local toxicity in the GI tract; (v) externally activated systems; and (vi) colloidal systems such as liposomes and microspheres. There is evidence for improved tolerability for a variety of drugs administered in novel delivery systems. However, the evidence for improved tolerability is complicated by the potential bias in adverse reaction reporting systems, and a lack of studies directly comparing conventional and modified release preparations. The technology now available to produce delivery systems which not only release drugs in a controlled and predetermined fashion, but which can also target to regions of the GI tract such as the colon, should allow greater control of therapy and potentially might minimise patient variables. However, the problem of variable GI transit times still eludes solution. Systems which rely on time to release drug might be more vulnerable to patient-to-patient variability than those which respond to local environments. The effect of food intake is more apparent on single-unit, nondisintegrating dosage forms, although of course none so far are immune from influence. The risk of new adverse effects resulting from such positional therapy with novel delivery devices must be considered. Understanding the mechanisms of induction of individual adverse effects can lead to advances in modes of delivery to decrease the potential for adverse reactions and events while maintaining therapeutic efficacy. Increased compliance can led to increased therapeutic control and hence safety. Each system has to be considered on its merits. No generalisations can be made, although invariably the modulation of high peak plasma concentrations diminishes adverse effects due to rapid absorption. PMID:8043223

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

    PubMed Central

    Kawana, Kei; Osuga, Yutaka; Fujii, Tomoyuki

    2013-01-01

    Cervical cancer is caused by high-risk human papillomaviruses (HPVs), and a unique characteristic of these is a PDZ (P¯SD-95/D¯lg/Z¯O-1-)binding motif in their E6 proteins. Through this motif HPV E6 interacts with a variety of PDZ domain-containing proteins and targets them mainly for degradation. These E6-PDZ interactions exhibit extraordinarily different functions in relation to HPV-induced malignancy, depending upon various cellular contexts; for example, Dlg and Scrib show different distribution patterns from what is seen in normal epithelium, both in localization and in amount, and their loss may be a late-stage marker in malignant progression. Recent studies show that interactions with specific forms of the proteins may have oncogenic potential. In addition, it is interesting that PDZ proteins make a contribution to the stabilization of E6 and viral episomal maintenance during the course of HPV life cycle. Various posttranslational modifications also greatly affect their functions. Phosphorylation of hDlg and hScrib by certain kinases regulates several important signaling cascades, and E6-PDZ interactions themselves are regulated through PKA-dependent phosphorylation. Thus these interactions naturally have great potential for both predictive and therapeutic applications, and, with development of screening tools for identifying novel targets of their interactions, comprehensive spatiotemporal analysis is currently underway. PMID:24093094

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

    PubMed Central

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

    2007-01-01

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

  13. GHRH Receptor Expression in Malignant Mixed Müllerian Tumors: A Potentially Targetable Biopredictor.

    PubMed

    Mackrides, Nicholas; Ganjei-Azar, Parvin; Perez, Roberto; Cui, Tengijiao; Block, Norman; Schally, Andrew V; Nadji, Mehrdad

    2016-03-01

    Malignant mixed Müllerian tumors (MMMTs) are aggressive malignant neoplasms with a high recurrence rate and poor prognosis. Despite advances in adjuvant therapies in recent years, the prognosis of these tumors has not improved. Growth hormone-releasing hormone (GHRH) is produced by a variety of malignant tumors and acts as a growth factor in an autocrine/paracrine manner. Its function requires the presence of its receptors to exert its effects on neoplastic cells. In this study, we evaluated the expression of GHRH receptors (GHRH-R) in a group of MMMTs. Thirty-one examples of MMMTs from endometrium, ovary, uterine tube, and pelvic peritoneum were retrieved from the files of Department of Pathology at the University of Miami, Jackson Memorial Hospital. Immunohistochemistry for GHRH-R was performed on paraffin sections and the staining results were evaluated separately in both epithelial and mesenchymal components of each tumor. The presence of pituitary type growth hormone-releasing hormone receptor mRNA and that of its biologically active splice variant were also evaluated by RT-PCR in 6 of the tumors. Positive immunohistochemical reaction for GHRH-R was detected in 30 tumors (96%). The epithelial and sarcomatous components were positive in 30 (96%), whereas one endometrial tumor was negative in both components. The mRNA for GHRH-R and its splice variant was found in all 6 tested tumors. This study shows that GHRH-R is expressed by the majority of MMMTs in both epithelial and mesenchymal components. This finding could potentially serve as a basis for therapeutic approaches using synthetic peptide antagonists of GHRH-R that have shown significant efficacy with minimal side effects in experimental models. PMID:26535981

  14. Oral Leukoplakia – an Update

    PubMed Central

    PARLATESCU, Ioanina; GHEORGHE, Carmen; COCULESCU, Elena; TOVARU, Serban

    2014-01-01

    The main purpose of this paper was to assess the current state of science on oral leukoplakia. Although it is considered a potentially malignant disorder the overall malignant progression of oral leukoplakia is of the order of 5% and even more. Nowadays there are no currently accepted markers to distinguish those that may progress to cancer from those that may not. The current golden standard is considered the presence of epithelial dysplasia on the tissue biopsy of the lesion. Proliferative verrucous leukoplakia is a rare form of OL which has multiple recurrences, is refractory to treatment and has malignant transformation in a short period. It is considered a true premalignant lesion. The management of oral leukoplakia varies from a "wait and see" attitude and topical chemopreventive agents to complete surgical removal. PMID:25553134

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

    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

  17. ZNF423 and ZNF521: EBF1 Antagonists of Potential Relevance in B-Lymphoid Malignancies

    PubMed Central

    Mesuraca, Maria; Chiarella, Emanuela; Scicchitano, Stefania; Codispoti, Bruna; Giordano, Marco; Nappo, Giovanna; Bond, Heather M.; Morrone, Giovanni

    2015-01-01

    The development of the B-lymphoid cell lineage is tightly controlled by the concerted action of a network of transcriptional and epigenetic regulators. EBF1, a central component of this network, is essential for B-lymphoid specification and commitment as well as for the maintenance of the B-cell identity. Genetic alterations causing loss of function of these B-lymphopoiesis regulators have been implicated in the pathogenesis of B-lymphoid malignancies, with particular regard to B-cell acute lymphoblastic leukaemias (B-ALLs), where their presence is frequently detected. The activity of the B-cell regulatory network may also be disrupted by the aberrant expression of inhibitory molecules. In particular, two multi-zinc finger transcription cofactors named ZNF423 and ZNF521 have been characterised as potent inhibitors of EBF1 and are emerging as potentially relevant contributors to the development of B-cell leukaemias. Here we will briefly review the current knowledge of these factors and discuss the importance of their functional cross talk with EBF1 in the development of B-cell malignancies. PMID:26788497

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

    PubMed

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

    2007-11-01

    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

  19. Swietenine: a potential oral hypoglycemic from Swietenia macrophylla seed.

    PubMed

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

    2009-06-01

    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

  20. CRISPR/Cas9-mediated gene knockout of NANOG and NANOGP8 decreases the malignant potential of prostate cancer cells

    PubMed Central

    Kawamura, Norihiko; Nimura, Keisuke; Nagano, Hiromichi; Yamaguchi, Sohei; Nonomura, Norio; Kaneda, Yasufumi

    2015-01-01

    NANOG expression in prostate cancer is highly correlated with cancer stem cell characteristics and resistance to androgen deprivation. However, it is not clear whether NANOG or its pseudogenes contribute to the malignant potential of cancer. We established NANOG- and NANOGP8-knockout DU145 prostate cancer cell lines using the CRISPR/Cas9 system. Knockouts of NANOG and NANOGP8 significantly attenuated malignant potential, including sphere formation, anchorage-independent growth, migration capability, and drug resistance, compared to parental DU145 cells. NANOG and NANOGP8 knockout did not inhibit in vitro cell proliferation, but in vivo tumorigenic potential decreased significantly. These phenotypes were recovered in NANOG- and NANOGP8-rescued cell lines. These results indicate that NANOG and NANOGP8 proteins are expressed in prostate cancer cell lines, and NANOG and NANOGP8 equally contribute to the high malignant potential of prostate cancer. PMID:26087476

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

    PubMed Central

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

    2016-01-01

    For various types of tumor therapy, it is suggested that co-targeting of tumor microenvironment, mainly tumor vasculature, mediates tumor response mechanisms. Immunohistochemistry for glucose transporter-1 (GLUT-1), carbonic anhydrase-IX (CAIX), Ki-67, and von Willebrand factor VIII for microvessel density (MVD) were performed on formalin-fixed paraffin-embedded samples of canine oral malignant neoplasms. Polarographic oxygen measurements (median pO2) and perfusion data via contrast-enhanced power Doppler ultrasound (median vascularity, median blood volume) provided additional information. Ninety-two samples were analyzed: sarcomas (n = 32), carcinomas (n = 30), and malignant melanomas (n = 30). Polarographic oxygen and perfusion data was available in 22.8% (sarcomas n = 9, carcinomas n = 7, melanomas n = 5), and 27.1% (sarcomas n = 10, carcinomas n = 8, melanomas n = 7) of cases, respectively. GLUT-1 expression was detected in 46.7% of all samples, and was generally weak. CAIX expression was found in 34.8% of all samples. Median Ki-67 score and MVD count was 19% and 17, respectively. The evaluation of the GLUT-1 score and continuous data showed significantly lower GLUT-1 levels in sarcomas (mean 5.1%, SD 6.2) versus carcinomas and melanomas (mean 16.5%/ 19.0%, SD 17.3/ 20.9, p = 0.001). The expression of CAIX correlated mildly positively with GLUT-1 (p = 0.018, rho = 0.250) as well as with Ki-67 (p = 0.014, rho = 0.295). MVD showed a significantly lower level in melanomas (mean 12.6, SD 7.7) versus sarcomas and carcinomas (mean 21.8/ 26.9, SD 13.0/20.4, p = 0.001). Median vascularity and blood volume were significantly lower in sarcomas (mean 10.4%, SD 11.0, and mean 6.3%, SD 6.5, respectively) versus carcinomas (mean 39.2%, SD 16.4 and mean 33.0%, SD 25.6, respectively) and melanomas (mean 36.0%, SD 18.3, and 31.5%, SD 24.5). Between the 3 histological groups, there was neither a significant difference in the GLUT-1 and CAIX score and continuous data, nor the Ki67 score, or polarographic oxygen measurements. GLUT-1 continuous data and Ki-67 (p<0.001, rho = 0.403), as well as Ki-67 and MVD (p = 0.029, rho = 0.228) correlated positively and a mild correlation was found between vascularity and GLUT-1 (p = 0.043, rho = 0.408). GLUT-1, CAIX, proliferative index and MVD levels were established as microenvironmental descriptors with the purpose of creating a baseline in order to follow changes seen in the tumor microenvironment after hypofractionated radiation with high doses. PMID:26906567

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

    PubMed

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

    2016-01-01

    For various types of tumor therapy, it is suggested that co-targeting of tumor microenvironment, mainly tumor vasculature, mediates tumor response mechanisms. Immunohistochemistry for glucose transporter-1 (GLUT-1), carbonic anhydrase-IX (CAIX), Ki-67, and von Willebrand factor VIII for microvessel density (MVD) were performed on formalin-fixed paraffin-embedded samples of canine oral malignant neoplasms. Polarographic oxygen measurements (median pO2) and perfusion data via contrast-enhanced power Doppler ultrasound (median vascularity, median blood volume) provided additional information. Ninety-two samples were analyzed: sarcomas (n = 32), carcinomas (n = 30), and malignant melanomas (n = 30). Polarographic oxygen and perfusion data was available in 22.8% (sarcomas n = 9, carcinomas n = 7, melanomas n = 5), and 27.1% (sarcomas n = 10, carcinomas n = 8, melanomas n = 7) of cases, respectively. GLUT-1 expression was detected in 46.7% of all samples, and was generally weak. CAIX expression was found in 34.8% of all samples. Median Ki-67 score and MVD count was 19% and 17, respectively. The evaluation of the GLUT-1 score and continuous data showed significantly lower GLUT-1 levels in sarcomas (mean 5.1%, SD 6.2) versus carcinomas and melanomas (mean 16.5%/ 19.0%, SD 17.3/ 20.9, p = 0.001). The expression of CAIX correlated mildly positively with GLUT-1 (p = 0.018, rho = 0.250) as well as with Ki-67 (p = 0.014, rho = 0.295). MVD showed a significantly lower level in melanomas (mean 12.6, SD 7.7) versus sarcomas and carcinomas (mean 21.8/ 26.9, SD 13.0/20.4, p = 0.001). Median vascularity and blood volume were significantly lower in sarcomas (mean 10.4%, SD 11.0, and mean 6.3%, SD 6.5, respectively) versus carcinomas (mean 39.2%, SD 16.4 and mean 33.0%, SD 25.6, respectively) and melanomas (mean 36.0%, SD 18.3, and 31.5%, SD 24.5). Between the 3 histological groups, there was neither a significant difference in the GLUT-1 and CAIX score and continuous data, nor the Ki67 score, or polarographic oxygen measurements. GLUT-1 continuous data and Ki-67 (p<0.001, rho = 0.403), as well as Ki-67 and MVD (p = 0.029, rho = 0.228) correlated positively and a mild correlation was found between vascularity and GLUT-1 (p = 0.043, rho = 0.408). GLUT-1, CAIX, proliferative index and MVD levels were established as microenvironmental descriptors with the purpose of creating a baseline in order to follow changes seen in the tumor microenvironment after hypofractionated radiation with high doses. PMID:26906567

  3. Glomus tumor of uncertain malignant potential of the lung: a case report and review of literature

    PubMed Central

    Wan, Peng-Zhi; Han, Qiang; Wang, En-Hua; Lin, Xu-Yong

    2015-01-01

    Glomus tumor is an uncommon tumor usually presenting in the dermis. Rarely, it occurred in visceral organs including stomach, liver and long. The majority of glomus tumors were benign. Herein, we present a case of glomus tumor located in the left lobe of the lung in a 49 year-old Chinese male. An irregular mass measuring 3 cm was detected by imaging examination because of his suffering from cough, dyspnea and chest pain. Histologically, the tumor is composed predominantly of sheets of ovoid to round cells with clear border, pale cytoplasm and fine granular chromatin. The mitotic count was less than 5 per 50 HPF. The tumor focally invaded the surrounding normal bronchial and alveolar tissue. Immunohistochemical staining showed that the cells were diffusely positive for SMA, caldesmon, and vimentin. The Ki-67 proliferation index was approximately 20%. Based on morphologic features and the immunohistochemical profile, the tumor was consistent with glomus tumor of uncertain malignant potential. PMID:26823902

  4. Disulfiram, an old drug with new potential therapeutic uses for human hematological malignancies.

    PubMed

    Conticello, Concetta; Martinetti, Daniela; Adamo, Luana; Buccheri, Simona; Giuffrida, Raffaella; Parrinello, Nunziatina; Lombardo, Laura; Anastasi, Gabriele; Amato, Gabriella; Cavalli, Maide; Chiarenza, Annalisa; De Maria, Ruggero; Giustolisi, Rosario; Gulisano, Massimo; Di Raimondo, Francesco

    2012-11-01

    Disulfiram (DSF) is an aldehyde dehydrogenase inhibitor currently used for the treatment of alcoholism. Here, we show that multiple myeloma (MM) cell lines and primary cells from newly diagnosed and relapsed/resistant patients affected by MM, acute myeloid and lymphoblastic leukemia are significantly sensitive to DSF alone and in combination with copper. These effects are present at doses lower than those achievable in vivo after DSF standard administration. The cytotoxic effect achieved by this treatment is comparable to that obtained by conventional chemotherapy and is absent in normal hematopoietic cells. In addition, we found that DSF plus copper induces loss of mitochondrial membrane potential, triggers reactive oxygen species (ROS) production and activates executioner caspases. DSF-copper-induced apoptosis and caspases activation are strongly reversed by antioxidant N-acetylcysteine, thus indicating a critical role of ROS. These results might suggest the use of the old drug DSF, alone or in combination with copper, in the treatment of hematological malignancies. PMID:22322883

  5. [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

    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

    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

  6. Epstein-Barr virus LMP1 modulates the malignant potential of gastric carcinoma cells involving apoptosis.

    PubMed Central

    Sheu, L. F.; Chen, A.; Wei, Y. H.; Ho, K. C.; Cheng, J. Y.; Meng, C. L.; Lee, W. H.

    1998-01-01

    About 10% of gastric carcinomas including lymphoepithelioma-like carcinoma and adenocarcinoma are associated with Epstein-Barr virus (EBV) infection. In EBV-associated gastric carcinomas, the tumor cells express Epstein-Barr nuclear antigen 1 (EBNA-1) but not EBNA-2, -3A, -3B, or -3C, leader protein, or latent membrane proteins (LMPs) because of gene methylation. Only a few exceptional cases have LMP1 expression in tumor cells as demonstrated by immunohistochemical studies. To elucidate the biological effects of LMP1 and the significance of its restricted expression in EBV-associated gastric carcinomas, the LMP1 gene was transferred into EBV-negative gastric carcinoma cell lines (SCM1 and TMC1) and into EBV-negative nasopharyngeal carcinoma (NPC) cells (HONE-1) as a control. The biological effects of LMP1 in gastric carcinoma cells were monitored in vitro and in vivo. These results showed that the consequence of LMP1 expression is a growth enhancement in NPC cells, but it is a growth suppression in gastric carcinoma cells. The LMP1-expressing gastric carcinoma cells had a reduced growth rate, colony-forming efficiency, mean colony size, and tumorigenicity and a lower malignant cytological grade. The reduced growth rate, colony-forming efficiency, and mean colony size were partially reversible in vitro with treatment with LMP1 antisense oligonucleotide. In addition, enhanced apoptosis was found in the LMP1-expressing gastric carcinoma cells. This suggests that LMP1 may negatively modulate the malignant potential of gastric carcinoma cells via an enhancement of apoptosis. We concluded that the restriction of LMP1 expression in EBV-associated gastric carcinomas may lead to a growth advantage for tumor cells by avoiding LMP1 apoptotic effects and immunologically mediated elimination. Images Figure 1 Figure 2 Figure 3 Figure 6 Figure 7 PMID:9422524

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

    PubMed

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

    2016-01-01

    The aetiology and pathogenesis of salivary gland malignancies remain unknown. To reveal novel molecular factors behind the development of salivary gland cancer, we performed gene expression analyses from Smgb-Tag mouse salivary gland samples. The overall purpose was to apply these results for clinical use to find new approaches for both possible therapeutic targets and more accurate diagnostic tools. Smgb-Tag mouse strain, in which salivary neoplasms arise through a dysplastic phase in submandibular glands, was investigated using genome-wide microarray expression analysis, ingenuity pathway analysis, RT-PCR, and immunohistochemistry. Thirty-eight human salivary gland adenoid cystic carcinoma samples were investigated using immunohistochemistry for validation purposes. Our genome-wide study showed that Ppp2r1b, a PP2A subunit encoding tumor suppressor gene, is underexpressed in submandibular gland tumors of Smgb-Tag mice. mTOR signaling pathway was significantly enriched and mTOR linked PP2A subunit gene B55 gamma was significantly underexpressed in the analyses. Furthermore, parallel immunohistochemical analysis of three PP2A inhibitors demonstrated that two PP2A inhibitors, CIP2A and SET, are highly expressed in both dysplastic and adenocarcinomatous tumors of the Smgb-Tag mice. In addition, all 38 investigated human salivary adenoid cystic carcinoma samples stained positively for CIP2A and most for SET. Finally, p-S6 staining showed activation of mTOR pathway in human adenoid cystic carcinoma samples. Our results suggest that PP2A inhibition either via PP2A subunit underexpression or PP2A inhibitor overexpression play an important role in the formation of salivary gland malignancy, potentially due to mTOR signaling activation. © 2015 Wiley Periodicals, Inc. PMID:26395031

  8. Cooperatively transcriptional and epigenetic regulation of sonic hedgehog overexpression drives malignant potential of breast cancer.

    PubMed

    Duan, Zhao-Heng; Wang, Hao-Chuan; Zhao, Dong-Mei; Ji, Xiao-Xin; Song, Min; Yang, Xiao-Jun; Cui, Wei

    2015-08-01

    Sonic hedgehog (Shh), a ligand of Hedgehog signaling pathway, is considered an important oncogene and an exciting potential therapeutic target in several cancers. Comprehensive understanding of the regulation mechanism of Shh in cancer cells is necessary to find an effective approach to selectively block its tumorigenic function. We and others previously demonstrated that nuclear factor-kappa B (NF-?B) activation and promoter hypomethylation contributed to the overexpression of Shh. However, the relationship between transcriptional and epigenetic regulation of Shh, and their roles in the malignant phenotype of cancer cells are still not clearly elucidated. In the present study, our data showed that the level of Shh was higher in breast cancer tissues with positive NF-?B nuclear staining and promoter hypomethylation. In addition, survival analysis revealed that Shh overexpression, but not hypomethylation and NF-?B nuclear staining, was a poor prognosis indicator for breast cancers. Moreover, in vitro data demonstrated that both NF-?B activation and hypomethylation in promoter region were positively associated with the overexpression of Shh. Mechanistically, the hypomethylation in Shh promoter could facilitate NF-?B binding to its site, and subsequently cooperate to induce transcription of Shh. Furthermore, the biological function data indicated that overexpressed Shh enhanced the self-renewal capacity and migration ability of breast cancer cells, which could be augmented by promoter demethylation and NF-?B activation. Overall, our findings reveal multiple and cooperative mechanisms of Shh upregulation in cancer cells, and the roles of Shh in tumor malignant behavior, thus suggesting a new strategy for therapeutic interventions to reduce Shh in tumors and improve patients' prognosis. PMID:25990213

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

    PubMed

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

    2014-07-01

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

  10. Oral 1.01: Phase II trial of amrubicin in patients with previously treated advanced thymic malignancies

    PubMed Central

    Wakelee, Heather A.; Padda, Sukhmani K.; Burns, Matthew; Spittler, A. J.; Riess, Jonathan W.; San Pedro-Salcedo, Melanie; Ramchandran, Kavitha J.; Gubens, Matthew A.; Neal, Joel W.; Loehrer, Patrick J.

    2015-01-01

    Background Limited treatment options exist for patients with thymic malignancies (TM), and chemotherapy efficacy is often restricted by cumulative toxicity such as neuropathy (taxanes) and cardiomyopathy (anthracyclines). Single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor with minimal cardiac toxicity, was investigated in TM patients in this trial. Methods This was an open-label single drug trial at two institutions in the United States (Stanford University and Indiana University). Eligible patients had TM [thymoma (T) or thymic carcinoma (TC)] with progression or relapse after at least one prior chemotherapy regimen, and adequate organ function including left ventricular ejection fraction (LVEF) of >50%. The initial treatment plan consisted of amrubicin at 40 mg/m2 IV days 1–3 repeated in 3-week cycles. Results From July 2011 to April 2014, a total of 33 patients (14T/19TC) were enrolled. There were 14 women and 19 men; age range of 30–81 years; 9 Asian, 1 African-American, 1 Hispanic and 22 non-Hispanic White patients. A high rate of febrile neutropenia (FN) led to an amended starting dose of 35 mg/m2 days 1–3 repeated in 3-week cycles. In total, 7 patients experienced FN with 1 related death. Other grade 3/4 related events included: thrombocytopenia (n=2), neutropenia without fever (n=3), hyponatremia (n=2), hypokalemia (n=2), anemia (n=7), lethargy/fatigue (n=7), perirectal abscess (n=2), palmar-plantar erythrodysesthesia (n=3), syncope (n=2), venous embolism (n=2), and 1 patient each with sepsis, oral abscess, mucositis, chest pain, and epigastric pain. Other toxicities were generally mild and well tolerated. No significant changes in LVEF were noted on serial echocardiograms. There were 6 partial responses (4T/2TC), 21 with stable disease, and 4 with progressive disease (PD) or death at or before first assessment for a response rate (RR) of 18% and a disease control rate (DCR) of 88% (29%/11% RR in T vs. TC and 100%/78% DCR in T vs. TC). All but 5 patients received at least 4 cycles, and 15 tolerated >10 cycles, with 38 cycles as the highest number to date. Three patients remain on therapy. Conclusions Amrubicin, at 35 mg/m2 IV days 1–3 on a 3-week cycle, shows promise as a single agent in pre-treated patients with T and TC with an 18% RR (29% T/11% TC) and no unexpected toxicity. DCRs of 100% in the T patients and 78% in the TC patients were observed. RR and DCR were higher in the T patients compared to the TC patients. Further exploration of amrubicin as a single drug or in combination is warranted in TM.

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

    PubMed Central

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

    2007-01-01

    Background: A preceding exploratory study (J. Clin. Pathol. 57(2004), 1201–1207) had shown that a karyometric assessment of nuclei from papillary urothelial neoplasms of low malignant potential (PUNLMP) revealed subtle differences in phenotype which correlated with recurrence of disease. Aim of the Study: To validate the results from the exploratory study on a larger sample size. Materials: 93 karyometric features were analyzed on haematoxylin and eosin-stained sections from 85 cases of PUNLMP. 45 cases were from patients who had a solitary PUNLMP lesion and were disease-free during a follow-up period of at least 8 years. The other 40 were from patients with a unifocal PUNLMP, with one or more recurrences in the follow-up. A combination of the previously defined classification functions together with a new P-index derived classification method was used in an attempt to classify cases and identify a biomarker of recurrence in PUNLMP lesions. Results: Validation was pursued by a number of separate approaches. First, the exact procedure from the exploratory study was applied to the large validation set. Second, since the discriminant function 2 of the exploratory study had been based on a small sample size, a new discriminant function was derived. The case classification showed a correct classification of 61% for non-recurrent and 74% for recurrent cases, respectively. Greater success was obtained by applying unsupervised learning technologies to take advantage of phenotypical composition (correct classification of 92%). This approach was validated by dividing the data into training and test sets with 2/3 of the cases assigned to the training sets, and 1/3 to the test sets, on a rotating basis, and validation of the classification rate was thus tested on three separate data sets by a leave-k-out process. The average correct classification was 92.8% (training set) and 84.6% (test set). Conclusions: Our validation study detected subvisual differences in chromatin organization state between non-recurrent and recurrent PUNLMP, thus allowing a very stable method of predicting recurrence of papillary urothelial neoplasms of low malignant potential by karyometry. PMID:17429141

  12. Antidotes for novel oral anticoagulants: current status and future potential.

    PubMed

    Crowther, Mark; Crowther, Mark A

    2015-08-01

    The direct thrombin inhibitor dabigatran and the anti-Xa agents rivaroxaban, edoxaban, and apixaban are a new generation of oral anticoagulants. Their advantage over the vitamin K antagonists is the lack of the need for monitoring and dose adjustment. Their main disadvantage is currently the absence of a specific reversal agent. Dabigatran's, unlike the anti-Xa agents, absorption can be reduced by activated charcoal if administered shortly after ingestion and it can be removed from the blood with hemodialysis. Prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa all show some activity in reversing the anticoagulant effect of these drugs but this is based on ex vivo, animal, and volunteer studies. It is unclear, which, if any, of these drugs is the most suitable for emergency reversal. Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal. These agents are currently in premarketing studies. PMID:26088576

  13. HDAC8, A Potential Therapeutic Target for the Treatment of Malignant Peripheral Nerve Sheath Tumors (MPNST)

    PubMed Central

    Lopez, Gonzalo; Bill, Kate Lynn J.; Bid, Hemant Kumar; Braggio, Danielle; Constantino, Dylan; Prudner, Bethany; Zewdu, Abeba; Batte, Kara; Lev, Dina; Pollock, Raphael E.

    2015-01-01

    Introduction HDAC isoform-specific inhibitors may improve the therapeutic window while limiting toxicities. Developing inhibitors against class I isoforms poses difficulties as they share high homology among their catalytic sites; however, HDAC8 is structurally unique compared to other class I isoforms. HDAC8 inhibitors are novel compounds and have affinity for class I HDAC isoforms demonstrating anti-cancer effects; little is known about their activity in malignant peripheral nerve sheath tumors (MPNST). Recently, we demonstrated anti-MPNST efficacy of HDAC8i in human and murine-derived MPNST pre-clinical models; we now seek to consider the potential therapeutic inhibition of HDAC8 in MPNST. Methods Four Human MPNST cell lines, a murine-derived MPNST cell line, and two HDAC8 inhibitors (PCI-34051, PCI-48012; Pharmacyclics, Inc. Sunnyvale, CA) were studied. Proliferation was determined using MTS and clonogenic assays. Effects on cell cycle were determined via PI FACS analysis; effects on apoptosis were determined using Annexin V-PI FACS analysis and cleaved caspase 3 expression. In vivo growth effects of HDAC8i were evaluated using MPNST xenograft models. 2D gel electrophoresis and mass spectrometry were used to identify potential HDAC8 deacetylation substrates. Results HDAC8i induced cell growth inhibition and marked S-phase cell cycle arrest in human and murine-derived MPNST cells. Relative to control, HDAC8i induced apoptosis in both human and murine-derived MPNST cells. HDAC8i exhibited significant effects on MPNST xenograft growth (p=0.001) and tumor weight (p=0.02). Four potential HDAC8 substrate targets were identified using a proteomic approach: PARK7, HMGB1, PGAM1, PRDX6. Conclusions MPNST is an aggressive sarcoma that is notoriously therapy-resistant, hence the urgent need for improved anti-MPNST therapies. HDAC8 inhibition may be useful for MPNST by improving efficacy while limiting toxicities as compared to pan-HDACis. PMID:26200462

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

    NASA Astrophysics Data System (ADS)

    Yeh, Chia-Hsien; Hsu, Yih-Chih

    2015-03-01

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

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

    PubMed

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

    2013-05-01

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

  16. Low molecular weight protein tyrosine phosphatase (LMWPTP) upregulation mediates malignant potential in colorectal cancer

    PubMed Central

    Hoekstra, Elmer; Kodach, Liudmila L.; Das, Asha M.; Ruela-de-Sousa, Roberta R.; Ferreira, Carmen V.; Hardwick, James C.; van der Woude, C. Janneke; Peppelenbosch, Maikel P.; ten Hagen, Timo L.M.; Fuhler, Gwenny M.

    2015-01-01

    Phosphatases have long been regarded as tumor suppressors, however there is emerging evidence for a tumor initiating role for some phosphatases in several forms of cancer. Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP; acid phosphatase 1 [ACP1]) is an 18 kDa enzyme that influences the phosphorylation of signaling pathway mediators involved in cancer and is thus postulated to be a tumor-promoting enzyme, but neither unequivocal clinical evidence nor convincing mechanistic actions for a role of LMWPTP have been identified. In the present study, we show that LMWPTP expression is not only significantly increased in colorectal cancer (CRC), but also follows a step-wise increase in different levels of dysplasia. Chemical inhibition of LMWPTP significantly reduces CRC growth. Furthermore, downregulation of LMWPTP in CRC leads to a reduced migration ability in both 2D- and 3D-migration assays, and sensitizes tumor cells to the chemotherapeutic agent 5-FU. In conclusion, this study shows that LMWPTP is not only overexpressed in colorectal cancer, but it is correlated with the malignant potential of this cancer, suggesting that this phosphatase may act as a predictive biomaker of CRC stage and represents a rational novel target in the treatment of this disease. PMID:25811796

  17. Low molecular weight protein tyrosine phosphatase (LMWPTP) upregulation mediates malignant potential in colorectal cancer.

    PubMed

    Hoekstra, Elmer; Kodach, Liudmila L; Das, Asha M; Ruela-de-Sousa, Roberta R; Ferreira, Carmen V; Hardwick, James C; van der Woude, C Janneke; Peppelenbosch, Maikel P; Ten Hagen, Timo L M; Fuhler, Gwenny M

    2015-04-10

    Phosphatases have long been regarded as tumor suppressors, however there is emerging evidence for a tumor initiating role for some phosphatases in several forms of cancer. Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP; acid phosphatase 1 [ACP1]) is an 18 kDa enzyme that influences the phosphorylation of signaling pathway mediators involved in cancer and is thus postulated to be a tumor-promoting enzyme, but neither unequivocal clinical evidence nor convincing mechanistic actions for a role of LMWPTP have been identified. In the present study, we show that LMWPTP expression is not only significantly increased in colorectal cancer (CRC), but also follows a step-wise increase in different levels of dysplasia. Chemical inhibition of LMWPTP significantly reduces CRC growth. Furthermore, downregulation of LMWPTP in CRC leads to a reduced migration ability in both 2D- and 3D-migration assays, and sensitizes tumor cells to the chemotherapeutic agent 5-FU. In conclusion, this study shows that LMWPTP is not only overexpressed in colorectal cancer, but it is correlated with the malignant potential of this cancer, suggesting that this phosphatase may act as a predictive biomaker of CRC stage and represents a rational novel target in the treatment of this disease. PMID:25811796

  18. Can Prostate-Specific Antigen Kinetics before Prostate Biopsy Predict the Malignant Potential of Prostate Cancer?

    PubMed Central

    Kim, Sang Jin; Jeong, Tae Yoong; Yoo, Dae Seon; Park, Jinsung; Cho, Seok; Kang, Seok Ho; Lee, Sang Hyub; Jeon, Seung Hyun; Lee, Tchun Yong

    2015-01-01

    Purpose To predict the malignant potential of prostate cancer (PCa) according to prostate-specific antigen velocity (PSAV), PSA density (PSAD), free/total PSA ratio (%fPSA), and digital rectal examination (DRE). Materials and Methods From January 2009 to December 2012, 548 adult male patients were diagnosed with PCa by prostate biopsy at four hospitals in Korea. We retrospectively analyzed 155 adult male patients with an initial PSA level ?10 ng/mL and whose PSA levels had been checked more than two times at least 6 months before they had been diagnosed with PCa, with test intervals of more than 3 months. Patients with a urinary tract infection, and patients who had previously undergone cystoscopy or surgery of the prostate were excluded. We separated patients into two groups according to Gleason sum [Gleason sum ?7 (n=134) or Gleason sum ?8 (n=21)] and the presence of extracapsular invasion [organ confined (n=129) or extracapsular invasion (n=26)]. Differences between the groups were compared. Results The group with a Gleason sum ?8 or extracapsular invasion of PCa showed high PSAV and significantly lower %fPSA. There were no significant differences in PSAD and the presence of an abnormality on DRE between two groups. Conclusion In PCa patients treated with other therapies besides prostatectomy, a high PSA velocity and a low %fPSA may predict high grade PCa with a Gleason sum ?8 or the presence of extracapsular invasion. PMID:26446628

  19. Functional and Biological Role of Endothelial Precursor Cells in Tumour Progression: A New Potential Therapeutic Target in Haematological Malignancies

    PubMed Central

    Reale, Antonia; Melaccio, Assunta; Lamanuzzi, Aurelia; Saltarella, Ilaria; Dammacco, Franco; Vacca, Angelo; Ria, Roberto

    2016-01-01

    It was believed that vasculogenesis occurred only during embryo life and that postnatal formation of vessels arose from angiogenesis. Recent findings demonstrate the existence of Endothelial Precursor Cells (EPCs), which take partin postnatal vasculogenesis. EPCs are recruited from the bone marrow under the stimulation of growth factors and cytokines and reach the sites of neovascularization in both physiological and pathological conditions such as malignancies where they contribute to the “angiogenic switch” and tumor progression. An implementation of circulating EPCs in the bloodstream of patients with haematological malignancies has been demonstrated. This increase is strictly related to the bone marrow microvessel density and correlated with a poor prognosis. The EPCs characterization is a very complex process and still under investigation. This literature review aims to provide an overview of the functional and biological role of EPCs in haematological malignancies and to investigate their potential as a new cancer therapeutic target. PMID:26788072

  20. Functional and Biological Role of Endothelial Precursor Cells in Tumour Progression: A New Potential Therapeutic Target in Haematological Malignancies.

    PubMed

    Reale, Antonia; Melaccio, Assunta; Lamanuzzi, Aurelia; Saltarella, Ilaria; Dammacco, Franco; Vacca, Angelo; Ria, Roberto

    2016-01-01

    It was believed that vasculogenesis occurred only during embryo life and that postnatal formation of vessels arose from angiogenesis. Recent findings demonstrate the existence of Endothelial Precursor Cells (EPCs), which take partin postnatal vasculogenesis. EPCs are recruited from the bone marrow under the stimulation of growth factors and cytokines and reach the sites of neovascularization in both physiological and pathological conditions such as malignancies where they contribute to the "angiogenic switch" and tumor progression. An implementation of circulating EPCs in the bloodstream of patients with haematological malignancies has been demonstrated. This increase is strictly related to the bone marrow microvessel density and correlated with a poor prognosis. The EPCs characterization is a very complex process and still under investigation. This literature review aims to provide an overview of the functional and biological role of EPCs in haematological malignancies and to investigate their potential as a new cancer therapeutic target. PMID:26788072

  1. Precancerous lesions of oral mucosa.

    PubMed

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

    2014-12-16

    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

  2. Precancerous lesions of oral mucosa

    PubMed Central

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

    2014-01-01

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

  3. Garlic allicin as a potential agent for controlling oral pathogens.

    PubMed

    Bachrach, Gilad; Jamil, Areen; Naor, Ronit; Tal, Golan; Ludmer, Zvi; Steinberg, Doron

    2011-11-01

    Garlic has been used medicinally throughout human history. Allicin is considered the most therapeutic constituent of garlic. This study tested the antimicrobial activity of garlic allicin on oral pathogens associated with dental caries and periodontitis. Allicin was found effective against all the tested bacteria. The broth dilution method revealed that planktonic growth of the cariogenic, gram-positive species Streptococcus mutans, S. sobrinus, and Actinomyces oris was inhibited by an allicin concentration of 600 ?g/mL or higher. Planktonic growth of the tested gram-negative periopathogenic species Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum was inhibited by a minimum allicin concentration of 300 ?g/mL. Porphyromonas gingivalis, an anaerobic, gram-negative pathogen and the bacterium most associated with chronic periodontitis, demonstrated the lowest sensitivity to allicin (2,400 ?g/mL). Gel zymography and the synthetic chromogenic substrate N(?)-benzoyl-L-arginine 4-nitroanilide hydrochloride demonstrated that allicin inhibits the proteases of P. gingivalis, including the arginine and lysine gingipains known as major virulence factors of this organism. A gingipain-inactivated mutant demonstrated high sensitivity to allicin (<300 ?g/mL), revealing that gingipains confer resistance to allicin. Live/dead staining followed by analysis with confocal laser scanning microscopy revealed that allicin was bactericidal to S. mutans grown in mature biofilms. However, this bactericidal effect was reduced as biofilm depth increased. In conclusion, these results support the traditional medicinal use of garlic and suggest the use of allicin for alleviating dental diseases. PMID:21548800

  4. Mucinous cystic tumour of low malignant potential presenting in a patient with prior non-seminatous germ cell tumour

    PubMed Central

    Chahal, Daljeet; Martens, Mildred; Kinahan, John

    2015-01-01

    Urachal neoplasms are rare entities which may be classified as cystic or non-cystic. Literature surrounding patient outcomes remains limited to non-cystic, urachal adenocarcinomas. Literature focusing on mucinous cystic neoplasms of the urachus is sparse. These mucinous cystic lesions may be subclassified as benign mucinous cystadenomas, mucinous cystic tumours of low malignant potential, and mucinous cystadenocarcinomas. Mucinous subtypes have the potential to behave aggressively and may result in pseudomyxoma peritonei. We describe here the case of a 37-year-old male with a mucinous cystic tumour of low malignant potential after prior right orchiectomy and left hydrocelectomy. This case raises the interesting possibility of multiple genitourinary neoplasms arising in a similar time frame. PMID:26664515

  5. [Changes in the redox potential of serum samples following in vitro irradiation--an indicator of malignant tumor growth].

    PubMed

    Hamann, D; Heinrich, H

    1989-01-01

    In serum samples of healthy persons and patients with malignant neoplasia the reduction-oxidation-potentials were determined. Measurements were made in untreated sera and after irradiation with different doses. Sera of healthy persons showed a decrease that of tumor patients an increase of redox-potential values. With this method malignant tumor growth can be demonstrated. It does not yet permit any statements on tumor localisation. On the other hand conclusions seem to be possible on growth speed of neoplasia. To our hitherto existing experiences estimations of redox-potential are applicable to the diagnosis of fast growing recurrences and metastases in tumor after-care, but can also support the therapeutic procedure decisively in defined differential diagnostic problems and in tumors of dignity in question. PMID:2608893

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

    SciTech Connect

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

    2007-07-15

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

  9. MicroRNA-214 and MicroRNA-126 Are Potential Biomarkers for Malignant Endothelial Proliferative Diseases.

    PubMed

    Heishima, Kazuki; Mori, Takashi; Ichikawa, Yukie; Sakai, Hiroki; Kuranaga, Yuki; Nakagawa, Takayuki; Tanaka, Yuiko; Okamura, Yasuhiko; Masuzawa, Mikio; Sugito, Nobuhiko; Murakami, Mami; Yamada, Nami; Akao, Yukihiro; Maruo, Kohji

    2015-01-01

    Malignant endothelial proliferative diseases including human angiosarcoma (AS) and canine hemangiosarcoma (HSA) are serious diseases with a grave prognosis. Establishing liquid biopsy-based biomarkers for screening has definite clinical utility; however, plasma miRNAs up- or down-regulated in these sarcomas have been unclear. For identifying possible diagnostic plasma miRNAs for these sarcomas, we investigated whether plasma miR-214 and miR-126, which miRNAs play important roles in angiogenesis and tumorigenesis, were elevated in malignant endothelial proliferative diseases. For this investigation, human angiosarcoma and canine hemangiosarcoma cell lines and clinical plasma samples of canine hemangiosarcoma were examined by performing miRNA qRT-PCR. We report here that human angiosarcoma and canine hemangiosarcoma cell lines over-secreted miR-214 and miR-126 via microvesicles; in addition, their levels in the plasma samples from canines with hemangiosarcoma were increased. Moreover, the surgical resection of primary tumors decreased the levels of plasma miR-214 and miR-126. Our findings suggest that these malignant endothelial proliferative diseases over-secreted miR-214 and miR-126, thus suggesting that these miRNAs have potential as diagnostic biomarkers for malignant endothelial proliferative diseases in canine and possible in human angiosarcoma. PMID:26512652

  10. MicroRNA-214 and MicroRNA-126 Are Potential Biomarkers for Malignant Endothelial Proliferative Diseases

    PubMed Central

    Heishima, Kazuki; Mori, Takashi; Ichikawa, Yukie; Sakai, Hiroki; Kuranaga, Yuki; Nakagawa, Takayuki; Tanaka, Yuiko; Okamura, Yasuhiko; Masuzawa, Mikio; Sugito, Nobuhiko; Murakami, Mami; Yamada, Nami; Akao, Yukihiro; Maruo, Kohji

    2015-01-01

    Malignant endothelial proliferative diseases including human angiosarcoma (AS) and canine hemangiosarcoma (HSA) are serious diseases with a grave prognosis. Establishing liquid biopsy-based biomarkers for screening has definite clinical utility; however, plasma miRNAs up- or down-regulated in these sarcomas have been unclear. For identifying possible diagnostic plasma miRNAs for these sarcomas, we investigated whether plasma miR-214 and miR-126, which miRNAs play important roles in angiogenesis and tumorigenesis, were elevated in malignant endothelial proliferative diseases. For this investigation, human angiosarcoma and canine hemangiosarcoma cell lines and clinical plasma samples of canine hemangiosarcoma were examined by performing miRNA qRT-PCR. We report here that human angiosarcoma and canine hemangiosarcoma cell lines over-secreted miR-214 and miR-126 via microvesicles; in addition, their levels in the plasma samples from canines with hemangiosarcoma were increased. Moreover, the surgical resection of primary tumors decreased the levels of plasma miR-214 and miR-126. Our findings suggest that these malignant endothelial proliferative diseases over-secreted miR-214 and miR-126, thus suggesting that these miRNAs have potential as diagnostic biomarkers for malignant endothelial proliferative diseases in canine and possible in human angiosarcoma. PMID:26512652

  11. Expression profiling of serous low malignant potential, low-grade, and high-grade tumors of the ovary.

    PubMed

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

    2005-11-15

    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 contributing to their phenotypes. Affymetrix U133 Plus 2.0 microarrays (Santa Clara, CA) were used to interrogate 80 microdissected serous LMP tumors and invasive ovarian malignancies along with 10 ovarian surface epithelium (OSE) brushings. Gene expression profiles for each tumor class were used to complete unsupervised hierarchical clustering analyses and identify differentially expressed genes contributing to these associations. Unsupervised hierarchical clustering analysis revealed a distinct separation between clusters containing borderline and high-grade lesions. The majority of low-grade tumors clustered with LMP tumors. Comparing OSE with high-grade and LMP expression profiles revealed enhanced expression of genes linked to cell proliferation, chromosomal instability, and epigenetic silencing in high-grade cancers, whereas LMP tumors displayed activated p53 signaling. The expression profiles of LMP, low-grade, and high-grade papillary serous ovarian carcinomas suggest that LMP tumors are distinct from high-grade cancers; however, they are remarkably similar to low-grade cancers. Prominent expression of p53 pathway members may play an important role in the LMP tumor phenotype. PMID:16288054

  12. Potential use of computer navigation in the treatment of primary benign and malignant tumors in children.

    PubMed

    Saidi, Kevan

    2012-06-01

    The treatment of benign and malignant primary bone tumors has progressed over time from relatively simple practice to complex resection and reconstruction techniques. Recently, computer-assisted orthopaedic surgery (CAOS) has been used to assist surgeons to enhance surgical precision in order to achieve these goals. Initially, software developed for CT-based spinal applications was used to perform simple intraoperative point localization. With advances in technique and software design, oncology surgeons have now performed joint sparing complex multiplanar osteotomies using combined CT and MRI image data with precision and accuracy. The purpose of this paper is to provide a review of the clinical progress to date, the different types of navigation available, methods for error management, and limitations of CAOS in the treatment of pediatric benign and malignant primary bone tumors. PMID:22488037

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

    PubMed Central

    Sato, Akinori

    2015-01-01

    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. PMID:25914545

  14. The metastatic potential of head and neck cutaneous malignant melanoma: is sentinel node biopsy useful?

    PubMed

    Main, B G; Coyle, M J; Godden, A; Godden, D R

    2014-04-01

    Results from a large multicentre trial suggest that sentinel lymph node biopsy examination may benefit disease-free survival in patients with cutaneous malignant melanoma of intermediate thickness, but this is controversial. We recorded the outcomes of patients with these lesions in the head and neck with specific reference to regional lymph node metastases, to find out whether routine sentinel lymph node biopsy examination would have been beneficial. We reviewed pathology databases, multidisciplinary outcomes, and notes for all patients managed by a regional melanoma service between 2004 and 2009, and recorded key characteristics of the tumours. Details on patients with malignant melanoma of intermediate thickness (1.2-3.5mm) were further analysed for the development of nodal metastases in the neck over a 3-year postoperative period. We compared our data with the rate of predicted nodal metastases generated from the trial. Of 132 patients with malignant melanoma of the head and neck, 33 (25%) had lesions of intermediate thickness, and nodal metastases developed in only one. The remaining 32 remained free of neck disease during the study period. Although trial data predicted that 16% (n=5 in this sample) would show signs of metastasis and require neck dissection, on the basis of our data, practice in our unit will not change. Sentinel node biopsy examination for melanoma remains controversial because the natural history of metastatic spread of disease is not fully understood. PMID:24518069

  15. Salivary Heparanase Level Is a Potential Biomarker to Diagnose and Prognose the Malignant Salivary Gland Tumor

    PubMed Central

    Wang, Xin; Liu, Yang; Zhu, Shengrong; Gong, Zhongjian

    2015-01-01

    Background Upregulation of heparanase has been reported in an increasing number of human cancer tissues. However, the level of salivary heparanase and its clinical significance in patients with salivary gland tumors remain unclear. Methods Salivary heparanase levels in patients with salivary gland tumors were detected using enzyme-linked immunosorbent assays (ELISAs) and the clinical significance was evaluated by analyzing the correlations among salivary heparanase levels, clinicopathological parameters, and clinical outcomes. Results The levels of salivary heparanase were significantly higher in patients with malignant salivary gland tumors than in benign tumors and normal controls (P<0.0001). High salivary heparanase levels were positively correlated with increased lymph node metastasis (P = 0.0235) and poorer tumor node metastasis stage (TNM) (P = 0.0183). Survival analyses revealed that high salivary heparanase levels were associated with worse overall survival (P = 0.0023) and disease-free survival (DFS) (P = 0.0025). Conclusions The study shows that salivary heparanase levels, as detected by the ELISAs, can be used to diagnose and provide an accurate prognosis for malignant salivary gland tumors. Salivary heparanase level was an independent predictor in patients with malignant salivary gland tumors. PMID:26569485

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

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

    2014-01-01

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

  18. Ovarian serous tumors of low malignant potential with nodal low-grade serous carcinoma.

    PubMed

    Djordjevic, Bojana; Malpica, Anais

    2012-07-01

    Serous tumor of low malignant potential (SLMP) and low-grade serous carcinoma (LGSC) are part of one biological continuum, whereby SLMP can transform into LGSC. It has been suggested that some nodal SLMPs arise from nodal endosalpingiosis and evolve independently in lymph nodes (rather than being related to the ovarian primary). In this article, we present the clinicopathologic features of 5 cases of nodal LGSC presenting in association with ovarian SLMP. Clinical information was obtained from the patients' charts. Pathologic features of the nodal LGSC, including lymph node location, size of and extent of involvement of tumor, architectural pattern, degree of cytologic atypia, mitotic index, and presence of psammoma bodies, were recorded. Ovarian SLMPs were noted for laterality, size, presence of surface excrescences, microinvasion, and micropapillary/cribriform pattern and for presence of autoimplants, invasive, and noninvasive implants. The distribution of any lymph nodes with nodal endosalpingiosis or SLMPs was also recorded. Patients ranged in age from 28 to 68 years (median, 32 y). In 4 cases, the diagnosis of nodal LGSC occurred at a different time from that of the ovarian SLMPs, ranging from 7 months before to 5 months after the ovarian tumor diagnosis. Nodal LGSC was detected in supraclavicular (2 cases), cervical, intramammary, and periaortic lymph nodes (1 case each). The gross lymph node size ranged from 0.9 to 2.5 cm (median, 1.3 cm). The tumors either replaced the entire lymph node or were found diffusely involving subcapsular and medullary sinuses or lymph node cortices. Tumor cells showed typical cytologic features of LGSC and no mitotic activity. In 2 cases, however, focal pleomorphic cells and 1 mitosis per 10 HPF were noted. Psammoma bodies were identified in all cases. When immunohistochemical analysis was performed, all tumors exhibited a profile in keeping with Müllerian origin. All ovarian tumors were well sampled and ranged in size from 0.1 to 13 cm (median, 2.5 cm). No ovarian SLMP tumors showed the micropapillary/cribriform pattern, whereas only focal microinvasion was detected in 3 cases. Four tumors had surface excrescences. All cases had noninvasive implants, and a single case also had invasive implants. Lymph node dissection was performed in 2 cases, revealing extensive endosalpingiosis in pelvic and periaortic lymph nodes and SLMP in pelvic lymph nodes. In 1 additional case, a single lymph node was sampled, revealing a nodal SLMP. Clinical follow-up ranged from 2 to 14 years (median, 9 y). All patients received postoperative chemotherapy. None of the patients experienced recurrence in pelvic or abdominal soft tissue. Two patients are free of disease. However, 2 patients, one with cervical and another with supraclavicular nodal LGSC, had recurrences at these sites and subsequently succumbed to metastatic disease. Both of these patients had pelvic and periaortic nodal SLMP and extensive nodal endosalpingiosis. Another patient, originally with supraclavicular LGSC, developed pelvic and abdominal lymphadenopathy, and is currently alive with disease. For the first time, we present a case series of patients with ovarian SLMP who, despite any evidence of LGSC in the pelvis or any pelvic recurrences, developed extrapelvic/extra-abdominal nodal LGSC. These patients also had endosalpingiosis and SLMP in pelvic and periaortic lymph nodes, suggesting that SLMP/LGSC tumors in lymph nodes may arise independently of the ovarian primary, progress along their own timeline, and undergo metastatic spread. Therefore, in patients with ovarian SLMP and extensive pelvic/periaortic nodal endosalpingiosis and/or SLMP, examination and follow-up of extrapelvic lymph nodes are warranted, even if the ovarian tumor lacks high-risk features of recurrence. PMID:22613998

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

    PubMed Central

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

    2015-01-01

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

  20. Data from human salivary proteome - A resource of potential biomarkers for oral cancer.

    PubMed

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

    2015-09-01

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

  1. Phase I study of OPB-51602, an oral inhibitor of signal transducer and activator of transcription 3, in patients with relapsed/refractory hematological malignancies

    PubMed Central

    Ogura, Michinori; Uchida, Toshiki; Terui, Yasuhito; Hayakawa, Fumihiko; Kobayashi, Yukio; Taniwaki, Masafumi; Takamatsu, Yasushi; Naoe, Tomoki; Tobinai, Kensei; Munakata, Wataru; Yamauchi, Takeshi; Kageyama, Akiko; Yuasa, Miyuki; Motoyama, Masaaki; Tsunoda, Takeshi; Hatake, Kiyohiko

    2015-01-01

    We carried out a multicenter dose-escalation phase I study of oral OPB-51602, a signal transducer and activator of transcription 3 phosphorylation inhibitor, in patients with relapsed or refractory hematological malignancies to evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics, and preliminary antitumor activity. Twenty patients were treated with OPB-51602 at doses of 1, 2, 3, 4, and 6 mg in the “3 + 3” dose escalation design. The most common treatment-related adverse events included nausea (55%), peripheral sensory neuropathy (45%), and diarrhea (40%). The most frequently observed grade 3 or 4 drug-related adverse events were neutropenia (20%), leukopenia (15%), lymphopenia (10%), and thrombocytopenia (10%). The MTD was 6 mg, with dose-limiting toxicities of grade 3 lactic acidosis and increased blood lactic acid levels observed in one of three patients and grade 1–2 peripheral neuropathy in three of three patients. The recommended dose was determined to be 4 mg. OPB-51602 was rapidly absorbed, and exposure tended to increase in a dose-dependent manner. Accumulation of OPB-51602 was seen with 4 weeks of multiple treatments. No clear therapeutic response was observed. Durable stable disease was observed in two patients with acute myeloid leukemia and one with myeloma. In conclusion, the MTD of OPB-51602 was 6 mg. OPB-51602 was safe and well tolerated in a dose range of 1–4 mg. However, long-term administration at higher doses was difficult with the daily dosing schedule, and no response was seen. Therefore, further clinical development of OPB-51602 for hematological malignancies with a daily dosing schedule was terminated. PMID:25912076

  2. Phase I study of OPB-51602, an oral inhibitor of signal transducer and activator of transcription 3, in patients with relapsed/refractory hematological malignancies.

    PubMed

    Ogura, Michinori; Uchida, Toshiki; Terui, Yasuhito; Hayakawa, Fumihiko; Kobayashi, Yukio; Taniwaki, Masafumi; Takamatsu, Yasushi; Naoe, Tomoki; Tobinai, Kensei; Munakata, Wataru; Yamauchi, Takeshi; Kageyama, Akiko; Yuasa, Miyuki; Motoyama, Masaaki; Tsunoda, Takeshi; Hatake, Kiyohiko

    2015-07-01

    We carried out a multicenter dose-escalation phase I study of oral OPB-51602, a signal transducer and activator of transcription 3 phosphorylation inhibitor, in patients with relapsed or refractory hematological malignancies to evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics, and preliminary antitumor activity. Twenty patients were treated with OPB-51602 at doses of 1, 2, 3, 4, and 6 mg in the "3 + 3" dose escalation design. The most common treatment-related adverse events included nausea (55%), peripheral sensory neuropathy (45%), and diarrhea (40%). The most frequently observed grade 3 or 4 drug-related adverse events were neutropenia (20%), leukopenia (15%), lymphopenia (10%), and thrombocytopenia (10%). The MTD was 6 mg, with dose-limiting toxicities of grade 3 lactic acidosis and increased blood lactic acid levels observed in one of three patients and grade 1-2 peripheral neuropathy in three of three patients. The recommended dose was determined to be 4 mg. OPB-51602 was rapidly absorbed, and exposure tended to increase in a dose-dependent manner. Accumulation of OPB-51602 was seen with 4 weeks of multiple treatments. No clear therapeutic response was observed. Durable stable disease was observed in two patients with acute myeloid leukemia and one with myeloma. In conclusion, the MTD of OPB-51602 was 6 mg. OPB-51602 was safe and well tolerated in a dose range of 1-4 mg. However, long-term administration at higher doses was difficult with the daily dosing schedule, and no response was seen. Therefore, further clinical development of OPB-51602 for hematological malignancies with a daily dosing schedule was terminated. PMID:25912076

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

    PubMed

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

    2015-12-01

    Malignant peripheral nerve sheath tumors (MPNST) are relatively rare neoplasms with poor prognosis. At present there is no effective treatment for MPNST other than surgical resection. Nonetheless, the anti-tumor effect of boron neutron capture therapy (BNCT) was recently demonstrated in two patients with MPNST. Subsequently, tumor-bearing nude mice subcutaneously transplanted with a human MPNST cell line were injected with p-borono-L-phenylalanine (L-BPA) and subjected to BNCT. Pathological studies then revealed that the MPNST cells were selectively destroyed by BNCT. PMID:26278348

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

    PubMed Central

    Xiao, Li; Nasu, Masanori

    2014-01-01

    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

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

    PubMed Central

    2014-01-01

    Background It is largely accepted that specific immunological parameters in solid malignancies are associated with patient’s prognosis. Recently a correlation of macrophage polarization with histomorphological parameters could also be shown in oral squamous cell carcinoma (oscc). The observed tumor derived peripheral immune tolerance could be associated with the macrophage polarization in regional tumor draining lymph nodes. So far there are no studies analyzing the macrophage polarization in cervical lymph nodes of oscc patients. In the present study we aimed to correlate macrophage polarization in different anatomical lymph node compartments of patients diagnosed with oscc with histopathologic parameters of the primary tumor (T-, N-, L-, V-, Pn-status, grading). Methods Tumor free (n = 37) and metastatic (n = 17) lymph nodes of T1 and T2 oscc patients were processed for immunohistochemistry to detect CD68, CD11c, CD163 and MRC1 positive cells. Samples were digitized using whole slide imaging and the number of cells expressing the aforementioned markers in the region of interest quantitatively analyzed. Results The malignancy of the primary tumor (defined by T-, L-, Pn-status, grading) correlated with the lymph node macrophage polarization. L1 and Pn1 tumor cases displayed a significantly (p < 0.05) decreased M1 and increased M2 polarization in the sinus of the lymph nodes. G3 cases presented a significantly (p < 0.05) increased M2 polarization in the sinus compared to G2 cases. T2 tumors had significantly (p < 0.05) increased M2 polarization in the interfollicular zone of regional lymph nodes compared to T1 tumors. Metastatic and non-metastatic lymph nodes did not differ regarding their macrophage polarization. Conclusions The current study revealed for the first time an influence of oscc on the macrophage polarization in regional lymph nodes. Markers of malignant behavior in the primary tumor were associated with a shift of macrophage polarization in lymph nodes from the anti-tumoral M1 type to the tumor-promoting M2 type. As tumor free and metastatic lymph nodes did not differ in terms of their macrophage polarization pattern, there must be other factors influencing the location for lymph node metastasis formation. PMID:25042135

  6. Sclerosing paraganglioma of the carotid body: a potential pitfall of malignancy.

    PubMed

    Santi, Raffaella; Franchi, Alessandro; Saladino, Valeria; Trovati, Massimo; Cenacchi, Giovanna; Squadrelli-Saraceno, Massimo; Nesi, Gabriella

    2015-06-01

    Paragangliomas (PGs) of the head and neck region are typically benign, slow-growing neuroendocrine tumours. At times, they may exhibit unusual histological features, such as prominent stromal sclerosis (sclerosing PG), which may raise concerns of malignancy. We describe a case of sclerosing PG of the carotid body, emphasizing the value of immunohistochemical stains for differential diagnosis. A 43-year-old woman presented with a painless lump on the neck. A magnetic resonance imaging scan demonstrated a hypervascular lesion of the carotid body, which was surgically excised. Grossly, the lesion measured 1.8 cm at maximum diameter. On microscopic examination, irregular nests and tiny bundles of neoplastic cells were found between thick bands of fibrous tissue. Focal nuclear cytomegaly and marked pleomorphism were noted. Neoplastic cells proved to be immunoreactive for chromogranin, synaptophysin and neuron specific enolase, but negative for cytokeratins, smooth muscle actin and CD34. Ultrastructurally, numerous mitochondria, rough endoplasmic reticulum structures and endocrine granules were seen in the cytoplasm of the tumour cells. On consideration of the above-mentioned clinico-pathological and ultrastructural findings a diagnosis of sclerosing PG was established. Sclerosing PG is a rare entity which may mimic a malignant neoplasm. The recognition of this unusual morphological variant of PG, together with appropriate immunostains, leads to the correct diagnosis. PMID:25194351

  7. KAT5 (Tip60) is a potential therapeutic target in malignant pleural mesothelioma.

    PubMed

    Cregan, Sian; McDonagh, Lauran; Gao, Yun; Barr, Martin P; O'Byrne, Kenneth J; Finn, Stephen P; Cuffe, Sinead; Gray, Steven G

    2016-03-01

    Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura. Asbestos exposure (through inhalation) is the most well established risk factor for mesothelioma. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Lysine acetyltransferases (KATs) including KAT5 have been linked with the development of cisplatin resistance. This gene may therefore be altered in MPM and could represent a novel candidate target for intervention. Using RT-PCR screening the expression of all known KAT5 variants was found to be markedly increased in malignant tumors compared to benign pleura. When separated according to histological subtype, KAT5 was significantly overexpressed in both the sarcomatoid and biphasic subgroups for all transcript variants. A panel of MPM cell lines including the normal pleural cells LP9 and Met5A was screened for expression of KAT5 variants. Treatment of cells with a small molecule inhibitor of KAT5 (MG-149) caused significant inhibition of cellular proliferation (p<0.0001), induction of apoptosis and was accompanied by significant induction of pro-inflammatory cytokines/chemokines. PMID:26780987

  8. Recent trends in prevention of oral cancer

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-01-01

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

  10. In Vitro Assessment of the Anticancer Potential of Evodiamine in Human Oral Cancer Cell Lines.

    PubMed

    Sachita, Khadka; Kim, Yongsoo; Yu, Hyun-Ju; Cho, Sung-Dae; Lee, Jeong-Sang

    2015-08-01

    Evodiamine, a bioactive alkaloid, has been regarded as having antioxidant, antiinflammatory, and anticancer properties. In the present study, we explored the effects of evodiamine on cell growth and apoptosis in human oral cancer cell lines. Our data revealed that evodiamine significantly inhibited the proliferation of human oral cancer cells and resulted in the cleavages of PARP (poly (ADP-ribose) polymerase) and caspase-3, in addition to causing the typical characteristics of apoptosis. Evodiamine also increased Bax protein levels and caused translocation of Bax into mitochondria and Bax oligomerization. In addition, evodiamine decreased expression of myeloid cell leukemia (Mcl-1) at the transcriptional modification, and knockdown of Mcl-1 clearly resulted in an increase in expression of Bax and active Bax, resulting in induction of apoptosis. Evodiamine reduced expression of phosphorylated AKT, and LY294002 potentiated evodiamine-induced apoptosis by regulating Mcl-1 protein. Our results suggest that evodiamine induces apoptosis in human oral cancer cells through the AKT pathway. These findings provide a rationale for its clinical application in the treatment of oral cancer. PMID:25903972

  11. Potential protective effects of oral administration of allicin on acrylamide-induced toxicity in male mice.

    PubMed

    Zhang, Lulu; Wang, Enting; Chen, Feng; Yan, Haiyang; Yuan, Yuan

    2013-08-01

    Acrylamide (AA) forms during the heating of starchy foods at high temperature, and is regarded as a potential genotoxic carcinogen. However, with the worldwide concern about the carcinogenicity of AA, how to reduce the toxicity of AA has become a hot research topic. In this study, we further discussed the effects of oral administration of allicin on AA-induced toxicity by determining the hematological, biochemical and immunological parameters in the serum, kidney, liver, and brain of male mice. Our data showed that the orally administered allicin of 5, 10, and 20 mg kg?¹ bw d?¹ could significantly decrease thiobarbituric reactive substances (TBARS) and myeloperoxidase (MPO) levels, and simultaneously remarkably increased the superoxide dismutase (SOD) activity, glutathione S-transferase (GST) and glutathione (GSH) levels in the kidney, liver, and brain of the AA-treated mice. Furthermore, oral administration of allicin not only significantly decreased aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), tumor necrosis factor ? (TNF-?), interleukin (IL)-1?, interleukin (IL)-6, reactive oxygen species (ROS), and 8-hydroxy-desoxyguanosine (8-OHdG), but also increased interleukin (IL)-10 in the serum of AA-treated mice. Therefore, it was concluded that oral administration of allicin had a significant in vivo protective effect against the AA induced toxicity. PMID:23760623

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

    PubMed Central

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

    2016-01-01

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

  13. Distribution of transient receptor potential melastatin-8-containing nerve fibers in rat oral and craniofacial structures.

    PubMed

    Yajima, Takehiro; Sato, Tadasu; Hosokawa, Hiroshi; Kondo, Teruyoshi; Saito, Masahiro; Shimauchi, Hidetoshi; Ichikawa, Hiroyuki

    2015-09-01

    The transient receptor potential melastatin-8 (TRPM8) is a cold and menthol receptor located in the sensory ganglia. Immunohistochemistry for TRPM8 was performed on oral and craniofacial structures of the rat. TRPM8-immunoreactive (-IR) nerve fibers were detected in the oral mucous membrane. In the gingiva, TRPM8-IR nerve fibers were abundant beneath and within crestal and outer epithelia. Such nerve fibers were also common beneath and within taste buds in the incisive papilla. In addition, TRPM8-immunoreactivity was expressed by some taste bud cells in the papilla. Lips, periodontal ligaments and salivary glands as well as masticatory muscles and temporomandibular joints were mostly devoid of TRPM8-IR nerve fibers. A double immunofluorescence study indicated different distribution patterns of nerve fibers containing TRPM8 and calcitonin gene-related peptide in oral and craniofacial tissues. Retrograde tracing method also indicated that TRPM8-IR nerve fibers in the gingiva and incisive papilla originate from small sensory neurons in the trigeminal ganglion. TRPM8 may be associated with cool, cold nociceptive (oral mucosa. PMID:25978347

  14. Diagnostic potential of ancillary molecular testing in differentiation of benign and malignant thyroid nodules.

    PubMed

    Bhatia, Parisha; Deniwar, Ahmed; Friedlander, Paul; Aslam, Rizwan; Kandil, Emad

    2015-03-01

    Fine needle aspiration (FNA) cytology, being the mainstay to diagnose thyroid nodules, does not provide definitive results in a subset of patients. The use of molecular markers testing has been described as a useful aid in differentiation of thyroid nodules that present with an indeterminate cytodiagnosis. Molecular tests, such as the Afirma gene classifier, mutational assay and immunohistochemical markers have been increasingly used to further increase the accuracy and defer unnecessary surgeries for benign thyroid nodules. However, in light of the current literature, their emerging roles in clinical practice are limited due to financial and technical limitations. Nevertheless, their synergistic implementation can predict the risk of malignancy and yield an accurate diagnosis. This review discusses the clinical utility of various molecular tests done on FNA indeterminate nodules to avoid diagnostic thyroidectomies and warrant the need of future multi-Institutional studies. PMID:25750270

  15. Oral cancer in the UAE: a multicenter, retrospective study

    PubMed Central

    Anis, Raeefa; Gaballah, Kamis

    2013-01-01

    Aim To determine the prevalence of various malignant oral lesions in the UAE and correlate cases of squamous cell carcinomas with age, gender, site, grade, clinical presentations at the time of diagnosis, and the prevalence of neck metastasis. Materials and methods A multicenter, retrospective study was conducted at four major hospitals in the UAE. The study was based on histopathology reports of biopsies of oral tissues. Results Of the 992 oral biopsy reports retrieved, 147 cases of malignant tumors were found which accounted for 14.9% of the total biopsies. Fifteen different types of malignant lesions were diagnosed, of which oral squamous cell carcinoma (OSCC) was the most prevalent and made up 11.4% of the overall oral biopsies retrieved. The commonest presentation of cancer was ulceration (31.17%), followed by lumps and white lesions. The most common site where the lesions were diagnosed was the tongue (51.9%), followed by the cheeks and lips. OSCC accounted for 77% of all malignancies reported. Neck dissections were conducted in only 20.8% of all OSCC cases diagnosed at Mafraq and Tawam hospitals, of which 43.75% showed evidence of neck metastasis. Conclusion Oral cancer is not an uncommon disease in the UAE. This may mandate more awareness campaigning, including screening procedures for early detection of cancerous lesions and other potentially malignant oral diseases. Elective neck dissections to detect lymph node metastasis should be more routinely performed, in particular for tongue carcinomas because of the early neck involvement potential. PMID:23985381

  16. Atonal homolog 1 protein stabilized by tumor necrosis factor ? induces high malignant potential in colon cancer cell line.

    PubMed

    Fukushima, Keita; Tsuchiya, Kiichiro; Kano, Yoshihito; Horita, Nobukatsu; Hibiya, Shuji; Hayashi, Ryohei; Kitagaki, Keisuke; Negi, Mariko; Itoh, Eisaku; Akashi, Takumi; Eishi, Yoshinobu; Oshima, Shigeru; Nagaishi, Takashi; Okamoto, Ryuichi; Nakamura, Tetsuya; Watanabe, Mamoru

    2015-08-01

    Patients with inflammatory bowel disease (IBD) have an increased risk of developing colitis-associated colorectal cancer (CAC). CAC cells often develop chemoresistance, resulting in a poorer prognosis than that of sporadic colorectal cancer (CRC). The mechanism by which CAC enhances malignant potential remains unknown. We have previously reported that the proteasomal degradation of the transcription factor Atonal homolog 1 (Atoh1) protein results in the non-mucinous form of CRC. It also remains unknown whether Atoh1 protein is expressed in CAC. Therefore, in the present study, we investigated whether Atoh1 protein stabilizes in CAC. Consequently, the treatment with TNF-? stabilized Atoh1 protein through the inactivation of GSK-3? via Akt, resulting in the mucinous form of CRC cell lines. Atoh1 protein also enriched cancer stem cells with upregulated Lgr5 expression and cells in G0/G1 cell cycle phase, resulting in both the chemoresistance to 5-fluorouracil and oxaliplatin and the promotion of cell migration. Immunofluorescence of the human mucinous CAC specimens showed the accumulation of NF-?B p65 at nuclei with the expression of Atoh1 in mucinous cancer. In conclusion, the inflammation associated with carcinogenesis may preserve the differentiation system of intestinal epithelial cell (IEC), resulting in the acquisition of both the mucinous phenotype and high malignant potential associated with the enrichment of cancer stem cell. PMID:26017781

  17. Atonal homolog 1 protein stabilized by tumor necrosis factor ? induces high malignant potential in colon cancer cell line

    PubMed Central

    Fukushima, Keita; Tsuchiya, Kiichiro; Kano, Yoshihito; Horita, Nobukatsu; Hibiya, Shuji; Hayashi, Ryohei; Kitagaki, Keisuke; Negi, Mariko; Itoh, Eisaku; Akashi, Takumi; Eishi, Yoshinobu; Oshima, Shigeru; Nagaishi, Takashi; Okamoto, Ryuichi; Nakamura, Tetsuya; Watanabe, Mamoru

    2015-01-01

    Patients with inflammatory bowel disease (IBD) have an increased risk of developing colitis-associated colorectal cancer (CAC). CAC cells often develop chemoresistance, resulting in a poorer prognosis than that of sporadic colorectal cancer (CRC). The mechanism by which CAC enhances malignant potential remains unknown. We have previously reported that the proteasomal degradation of the transcription factor Atonal homolog 1 (Atoh1) protein results in the non-mucinous form of CRC. It also remains unknown whether Atoh1 protein is expressed in CAC. Therefore, in the present study, we investigated whether Atoh1 protein stabilizes in CAC. Consequently, the treatment with TNF-? stabilized Atoh1 protein through the inactivation of GSK-3? via Akt, resulting in the mucinous form of CRC cell lines. Atoh1 protein also enriched cancer stem cells with upregulated Lgr5 expression and cells in G0/G1 cell cycle phase, resulting in both the chemoresistance to 5-fluorouracil and oxaliplatin and the promotion of cell migration. Immunofluorescence of the human mucinous CAC specimens showed the accumulation of NF-?B p65 at nuclei with the expression of Atoh1 in mucinous cancer. In conclusion, the inflammation associated with carcinogenesis may preserve the differentiation system of intestinal epithelial cell (IEC), resulting in the acquisition of both the mucinous phenotype and high malignant potential associated with the enrichment of cancer stem cell. PMID:26017781

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Iriti, Marcello; Varoni, Elena Maria

    2013-01-01

    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

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

    PubMed

    Iriti, Marcello; Varoni, Elena Maria

    2013-07-01

    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

  1. PBEF1/NAmPRTase/Visfatin: a potential malignant astrocytoma/glioblastoma serum marker with prognostic value.

    PubMed

    Reddy, P Sreekanth; Umesh, Srikantha; Thota, Balaram; Tandon, Ashwani; Pandey, Paritosh; Hegde, A S; Balasubramaniam, Anandh; Chandramouli, B A; Santosh, Vani; Rao, M R S; Kondaiah, Paturu; Somasundaram, Kumaravel

    2008-05-01

    Malignant astrocytomas comprise anaplastic astrocytoma (AA; grade III) and Glioblastoma (GBM; grade IV). GBM is the most malignant with a median survival of 10-12 months in patients. Using cDNA microarray based expression profiling of different grades of astrocytomas, we identified several fold increased levels of PBEF1 transcripts in GBM samples. Pre-B-cell colony enhancing factor 1 gene (PBEF1) encodes Nicotinamide phosphoribosyltransferase (NAmPRTase), which catalyses the rate limiting step in the salvage pathway of NAD metabolism in mammalian cells. Further validation using real time RT-qPCR on an independent set of tumor samples (n=91) and normal brain samples (n=9), GBM specific higher expression of PBEF1 was confirmed. Immunohistochemical staining for PBEF1 on a subset of the above samples largely reinforced our finding. We carried out ELISA analysis on serum samples of astrocytoma patients to determine whether this protein levels would correlate with the presence of tumor and tumor grade. PBEF1 serum levels were substantially elevated in many of the AA and GBM patients. Statistical analysis of these data indicates that in patients with astrocytoma, serum PBEF1 levels correlate with tumor grade and is highest in GBM. Immunohistochemical analysis of an independent set of 51 retrospective GBM cases with known survival data revealed that PBEF1 expression in the tumor tissue along with its co-expression with p53 was associated with poor survival. Thus, we have identified PBEF1 as a potential malignant astrocytoma serum marker and prognostic indicator among GBMs. PMID:18728403

  2. miR-193a-3p is a potential tumor suppressor in malignant pleural mesothelioma

    PubMed Central

    Cheng, Yuen Yee; Hanh, Jacky; Weiss, Jocelyn; Mugridge, Nancy; Wright, Casey M.; Linton, Anthony; Kao, Steven C.; Edelman, J. James B.; Vallely, Michael P.; McCaughan, Brian C.; Cooper, Wendy; Klebe, Sonja; Lin, Ruby C.Y.; Brahmbhatt, Himanshu; MacDiarmid, Jennifer; van Zandwijk, Nico; Reid, Glen

    2015-01-01

    Malignant pleural mesothelioma (MPM) is an asbestos-induced cancer with poor prognosis that displays characteristic alterations in microRNA expression. Recently it was reported that the expression of a subset of microRNAs can distinguish between MPM and adenocarcinoma of the lung. However, the functional importance of these changes has yet to be investigated. We compared expression of miR-192, miR-193a-3p and the miR-200 family in normal pleura and MPM tumor specimens and found a statistically significant reduction in the levels of miR-193a-3p (3.1-fold) and miR-192 (2.8-fold) in MPM. Transfection of MPM cells with a miR-193a-3p mimic resulted in inhibition of growth and an induction of apoptosis and necrosis in vitro. The growth inhibitory effects of miR-193a-3p were associated with a decrease in MCL1 expression and were recapitulated by RNAi-mediated MCL1 silencing. Targeted delivery of miR-193a-3p mimic using EDV minicells inhibited MPM xenograft tumour growth, and was associated with increased apoptosis. In conclusion, miR-193a-3p appears to have importance in the biology of MPM and may represent a target for therapeutic intervention. PMID:26125439

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

    PubMed

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

    2014-11-01

    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

  4. miR-193a-3p is a potential tumor suppressor in malignant pleural mesothelioma.

    PubMed

    Williams, Marissa; Kirschner, Michaela B; Cheng, Yuen Yee; Hanh, Jacky; Weiss, Jocelyn; Mugridge, Nancy; Wright, Casey M; Linton, Anthony; Kao, Steven C; Edelman, J James B; Vallely, Michael P; McCaughan, Brian C; Cooper, Wendy; Klebe, Sonja; Lin, Ruby C Y; Brahmbhatt, Himanshu; MacDiarmid, Jennifer; van Zandwijk, Nico; Reid, Glen

    2015-09-15

    Malignant pleural mesothelioma (MPM) is an asbestos-induced cancer with poor prognosis that displays characteristic alterations in microRNA expression. Recently it was reported that the expression of a subset of microRNAs can distinguish between MPM and adenocarcinoma of the lung. However, the functional importance of these changes has yet to be investigated. We compared expression of miR-192, miR-193a-3p and the miR-200 family in normal pleura and MPM tumor specimens and found a statistically significant reduction in the levels of miR-193a-3p (3.1-fold) and miR-192 (2.8-fold) in MPM. Transfection of MPM cells with a miR-193a-3p mimic resulted in inhibition of growth and an induction of apoptosis and necrosis in vitro. The growth inhibitory effects of miR-193a-3p were associated with a decrease in MCL1 expression and were recapitulated by RNAi-mediated MCL1 silencing. Targeted delivery of miR-193a-3p mimic using EDV minicells inhibited MPM xenograft tumour growth, and was associated with increased apoptosis. In conclusion, miR-193a-3p appears to have importance in the biology of MPM and may represent a target for therapeutic intervention. PMID:26125439

  5. Antiepileptic drugs: are women aware of interactions with oral contraceptives and potential teratogenicity?

    PubMed

    Pack, Alison M; Davis, Anne R; Kritzer, Jordana; Yoon, Ava; Camus, Adela

    2009-04-01

    Women with epilepsy (WWE)'s knowledge of the interaction between antiepileptic drugs (AEDs) and oral contraceptives (OCs) and the potential teratogenicity of AEDs has received limited study. We conducted a cross-sectional questionnaire study (English or Spanish) among young WWE (18-44 years) to assess demographic characteristics, current AED use, and knowledge of AED interactions with OCs and teratogenicity. We used the Food and Drug Administration's classification system to categorize each AED's teratogenic potential. Participants (n=148) had a mean age of 32 years (SD 8); 32% spoke Spanish and described themselves as Hispanic. Among women prescribed a cytochrome p450-inducing AED, 65% were unaware of decreased OC efficacy. Forty percent of those prescribed Category D AEDs were unaware of potential teratogenic effects. WWE have limited knowledge of the potential interaction between AEDs and OCs and the teratogenic effects of AEDs. Educational efforts should highlight the reproductive health effects of AEDs in WWE. PMID:19435578

  6. Vertex potentials evoked by nociceptive laser stimulation of oral mucosa: a comparison of four stimulation paradigms.

    PubMed

    Svensson, P; Arendt-Nielsen, L; Kaaber, S; Bjerring, P

    1992-01-01

    A new method for quantitative assessment of oral mucosal nociception and analgesia has been introduced using vertex potentials elicited by nociceptive argon laser stimuli. Four different stimulation paradigms (long, random, warning, and self-triggered) were compared to determine which technique elicited the most reproducible vertex potentials. A warning stimulation paradigm applied on the tongue and hand elicited vertical potentials with smaller amplitudes, lowest intraindividual coefficient of variation (16.5% and 7.9%, respectively), and highest reproducibility. The latency of the major negative peak was not affected significantly by different stimulation paradigms. The high reproducibility of vertical potentials elicited by the warning stimulation may be ascribed to a standardized psychological state of the subjects. PMID:1298490

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

    PubMed Central

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

    2013-01-01

    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 μg/mL to 35.64 μg/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

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

    PubMed

    Shelleh, Hamdi H

    2012-05-01

    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

  9. Malignant hyperthermia.

    PubMed Central

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

    1998-01-01

    Malignant hyperthermia is a rare autosomal dominant trait that predisposes affected individuals to great danger when exposed to certain anaesthetic triggering agents (such as potent volatile anaesthetics and succinylcholine). A sudden hypermetabolic reaction in skeletal muscle leading to hyperthermia and massive rhabdomyolysis can occur. The ultimate treatment is dantrolene sodium a nonspecific muscle relaxant. Certain precautions should be taken before anaesthesia of patients known to be susceptible to malignant hyperthermia. These include the prohibition of the use of triggering agents, monitoring of central body temperature and expired CO2, and immediate availability of dantrolene. In addition, careful cleansing of the anaesthesia machine of vapours of halogenated agents is recommended. If these measures are taken, the chances of an MH episode are greatly reduced. When malignant hyperthermia-does occur in the operating room, prompt recognition and treatment usually prevent a potentially fatal outcome. The most reliable test to establish susceptibility to malignant hyperthermia is currently the in vitro caffeine-halothane contracture test. It is hoped that in the future a genetic test will be available. PMID:9538480

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

    PubMed Central

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

    2015-01-01

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

  11. Osteogenic Potential of Human Oral-Periosteal Cells (PCs) Isolated From Different Oral Origin: An In Vitro Study.

    PubMed

    Ceccarelli, Gabriele; Graziano, Antonio; Benedetti, Laura; Imbriani, Marcello; Romano, Federica; Ferrarotti, Francesco; Aimetti, Mario; Cusella De Angelis, Gabriella M

    2016-03-01

    The periosteum is a specialized connective tissue containing multipotent stem cells capable of bone formation. In this study, we aimed at demonstrating that human oral periosteal cells derived from three different oral sites (upper vestibule, lower vestibule, and hard palate) represent an innovative cell source for maxillo-facial tissue engineering applications in terms of accessibility and self-commitment towards osteogenic lineage. Periosteal cells (PCs) were isolated from patients with different ages (20-30 yy, 40-50 yy, 50-60 yy); we then analyzed the in vitro proliferation capacity and the bone self-commitment of cell clones culturing them without any osteogenic supplement to support their differentiation. We found that oral PCs, independently of their origin and age of patients, are mesenchymal stem cells with stem cell characteristics (clonogenical and proliferative activity) and that, even in absence of any osteogenic induction, they undertake the osteoblast lineage after 45 days of culture. These results suggest that oral periosteal cells could replace mesenchymal cells from bone marrow in oral tissue-engineering applications. J. Cell. Physiol. 231: 607-612, 2016. © 2015 Wiley Periodicals, Inc. PMID:26206324

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

    PubMed Central

    Vadhan-Raj, Saroj; Goldberg, Jenna D; Perales, Miguel-Angel; Berger, Dietmar P; Brink, Marcel RM

    2013-01-01

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

  13. Clinical Evaluation of Specific Oral Manifestations in Pediatric Patients with Ascertained versus Potential Coeliac Disease: A Cross-Sectional Study

    PubMed Central

    Matacena, Giada; Costa, Stefano; Magazzù, Giuseppe

    2014-01-01

    Patients involved on coeliac disease (CD) have atypical symptoms and often remain undiagnosed. Specific oral manifestations are effective risk indicators of CD and for this reason an early diagnosis with a consequent better prognosis can be performed by the dentist. There are not researches analysing the frequency of these oral manifestations in potential coeliac patients. The aim of this study is to investigate the oral hard and soft tissue lesions in potential and ascertained coeliac children in comparison with healthy controls. 50 ascertained children, 21 potential coeliac patients, and 54 controls were recruited and the oral examination was performed. The overall oral lesions were more frequently present in CD patients than in controls. The prevalence of oral soft tissue lesions was 62% in ascertained coeliac, 76.2% in potential coeliac patients, and 12.96% in controls (P < 0.05). Clinical dental delayed eruption was observed in 38% of the ascertained coeliac and 42.5% of the potential coeliac versus 11.11% of the controls (P < 0.05). The prevalence of specific enamel defects (SED) was 48% in ascertained coeliac and 19% in potential coeliac versus 0% in controls (P < 0.05; OR = 3.923). The SED seem to be genetically related to the histological damage and villous atrophy. PMID:25197270

  14. Role of micronucleus in oral exfoliative cytology

    PubMed Central

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

    2015-01-01

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

  15. Malignancies After Heart Transplant.

    PubMed

    Lateef, Noman; Abdul Basit, Kalid; Abbasi, Nadeem; Kazmi, Syed Murtaza Hasan; Ansari, Abdul Basit; Shah, Mudassir

    2016-02-01

    Along with graft vasculopathy, malignancies comprise a major complication after heart transplant, with a rate of occurrence of 39.1% in 10 years. Skin cancers and posttransplant lymphoproliferative disorder are more common in adults, whereas lymphoma is more often shown in children. A major cause of malignancies after heart transplant is the use of increased doses of prophylactics needed during immunosuppressive therapy. Data, however, are scarce regarding the association between a particular immunosuppressive drug and a posttransplant malignancy. Compared with the general population, recipients have a higher incidence of malignancies after heart transplant, with an early onset and more aggressive disease. Solid tumors known to occur in heart transplant recipients include lung cancer, bladder and prostate carcinoma, adenocarcinoma of the oral cavity, stomach cancer, and bowel cancer, although the incidence is rare. The risk factors for development of a malignancy after heart transplant are the same as for the nontransplant population. PMID:26643469

  16. Nodal endosalpingiosis in ovarian serous tumors of low malignant potential with lymph node involvement: a case for a precursor lesion.

    PubMed

    Djordjevic, Bojana; Clement-Kruzel, Stacia; Atkinson, Neely E; Malpica, Anais

    2010-10-01

    Lymph node involvement (LNI) in ovarian serous tumors of low malignant potential (OSLMP) upstages 22% of patients. The origin of LNI has been a subject of debate in the literature. The purpose of this study was to investigate the role of nodal endosalpingiosis in the pathogenesis of this entity. We first examined the frequency of nodal endosalpingiosis in 30 OSLMP cases, 30 cervical adenocarcinoma cases, and 30 endometrial endometrioid adenocarcinoma cases. The rate of nodal endosalpingiosis was significantly higher in OSLMP cases (33%) compared with both cervical (0%, P<0.0001) and endometrial tumor cases (3%, P=0.0015). We then compared the frequency of nodal endosalpingiosis in 36 cases of OSLMP with LNI and 36 cases of OSLMP without LNI. The rate of nodal endosalpingiosis was significantly higher in OSLMP with LNI (66%) than in OSLMP without LNI (14%, P<0.0001). We further investigated the cohort cases of OSLMP with LNI by recording the presence of nodal endosalpingiosis and LNI in each individual lymph node in every case. This analysis revealed that nodal endosalpingiosis and LNI appear together in the same lymph nodes at a much higher rate than would be expected by random chance alone (OR=71.2, P<0.0001). Lastly, in OSLMP cases with LNI, we recorded the types of LNI patterns. We found that the intraglandular pattern was present in a higher percentage of cases with nodal endosalpingiosis (50%) than in cases without nodal endosalpingiosis (8%, P=0.0253). Overall, the intraglandular pattern of LNI appeared in 36% of OSLMP cases with LNI. In this study, we show that nodal endosalpingiosis not only occurs more commonly in OSLMP compared with other Müllerian malignancies, but also in OSLMP with LNI compared with OSLMP without LNI. For the first time, we demonstrate a statistically significant association between endosalpingiosis and the intraglandular pattern of LNI, and we propose that in up to a third of patients with OSLMP and LNI, nodal foci of serous tumor of low malignant potential may derive independently, from nodal endosalpingiosis. This result contributes to the understanding of the pathogenesis of extraovarian disease in cases of OSLMP and has important implications for patient management and follow-up. PMID:20871218

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

    PubMed

    Chamberland, John P; Moon, Hyun-Seuk

    2015-03-01

    Omega-3 fatty acids (also called ?-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

  18. DNA hypermethylation as an epigenetic mark for oral cancer diagnosis.

    PubMed

    Radhakrishnan, Raghu; Kabekkodu, Shamaprasad; Satyamoorthy, Kapaettu

    2011-10-01

    Oral cancer is the largest group of cancers which fall into the head and neck category. While genetic alterations in oral cancer have long been documented, the effect of epigenetic changes is more recent. The recent explosion in science of how chromatin organization modulates the gene expression has highlighted the epigenetic mechanism of oral cancer pathogenesis. DNA methylation, which is an important epigenetic marker, is perhaps the best characterized chemical modification of mammalian DNA and provides a stable, heritable, and critical component of epigenetic regulation. This review attempts to decipher the epigenetic aspects of oral cancer by evaluating the DNA methylation status through its various stages from normal to potentially malignant to malignant states. In doing so, we emphasize DNA methylation as a novel biomarker in oral cancer research, thus opening newer avenues in oral cancer research. PMID:21649736

  19. Transmission of diverse oral bacteria to murine placenta: evidence for the oral microbiome as a potential source of intrauterine infection.

    PubMed

    Fardini, Yann; Chung, Peter; Dumm, Rochelle; Joshi, Nishiant; Han, Yiping W

    2010-04-01

    Microbial infection of the intrauterine environment is a major cause of preterm birth. The current paradigm indicates that intrauterine infections predominantly originate from the vaginal tract, with the organisms ascending into the sterile uterus. With the improvements in technology, an increasing number of bacterial species have been identified in intrauterine infections that do not belong to the vaginal microflora. We have demonstrated previously that intrauterine infections can originate from the oral cavity following hematogenous transmission. In this study, we begin to systemically examine what proportion of the oral microbiome can translocate to the placenta. Pooled saliva and pooled subgingival plaque samples were injected into pregnant mice through tail veins to mimic bacteremia, which occurs frequently during periodontal infections. The microbial species colonizing the murine placenta were detected using 16S rRNA gene-based PCR and clone analysis. A diverse group of bacterial species were identified, many of which have been associated with adverse pregnancy outcomes in humans although their sources of infection were not determined. Interestingly, the majority of these species were oral commensal organisms. This may be due to a dose effect but may also indicate a unique role of commensal species in intrauterine infection. In addition, a number of species were selectively "enriched" during the translocation, with a higher prevalence in the placenta than in the pooled saliva or subgingival plaque samples. These observations indicate that the placental translocation was species specific. This study provides the first insight into the diversity of oral bacteria associated with intrauterine infection. PMID:20123706

  20. Incidental Finding of a Rare Urachal Pathology: Urachal Mucinous Cystic Tumour of Low Malignant Potential

    PubMed Central

    Wang, Luke L.; Liddell, Heath; Tanny, Sharman Tan; Norris, Briony; Appu, Sree; Pan, David

    2016-01-01

    Urachal mucinous cystic tumours are rare pathological findings with only 23 previously reported cases in the literature. We present the case of a 54-year-old man with an incidentally found urachal mucinous cystic tumour laparoscopically excised. With its known potential to cause pseudomyxoma peritonei, complete surgical excision is important. Long-term cystoscopic and radiological surveillance is also required.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2011-01-01

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

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

    PubMed Central

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

    2000-01-01

    Systemic and superficial fungal infections are a major problem among immunocompromised patients with hematological malignancy. A double-blind, double-placebo, randomized, multicenter trial was performed to compare the efficacy and safety of itraconazole oral solution (2.5 mg/kg of body weight twice a day) with amphotericin B capsules (500 mg orally four times a day) for prophylaxis of systemic and superficial fungal infection. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (>0.5 × 109 neutrophils/liter) or up to a maximum of 3 days following the end of neutropenia, unless a systemic fungal infection was documented or suspected. The maximum treatment duration was 56 days. In the intent-to-treat population, invasive aspergillosis was noted in 5 (1.8%) of the 281 patients assigned to itraconazole oral solution and in 9 (3.3%) of the 276 patients assigned to oral amphotericin B; of these, 1 and 4 patients died, respectively. Proven systemic fungal infection (including invasive aspergillosis) occurred in 8 patients (2.8%) who received itraconazole, compared with 13 (4.7%) who received oral amphotericin B. Itraconazole significantly reduced the incidence of superficial fungal infections as compared to oral amphotericin B (2 [1%] versus 13 [5%]; P = 0.004). Although the incidences of suspected fungal infection (including fever of unknown origin) were not different between the groups, fewer patients were administered intravenous systemic antifungals (mainly intravenous amphotericin B) in the group receiving itraconazole than in the group receiving oral amphotericin B (114 [41%] versus 132 [48%]; P = 0.066). Adequate plasma itraconazole levels were achieved in about 80% of the patients from 1 week after the start of treatment. In both groups, the trial medication was safe and well tolerated. Prophylactic administration of itraconazole oral solution significantly reduces superficial fungal infection in patients with hematological malignancies and neutropenia. The incidence of proven systemic fungal infections, the number of deaths due to deep fungal infections, and the use of systemic antifungals tended to be lower in the itraconazole-treated group than in the amphotericin B-treated group, without statistical significance. Itraconazole oral solution is a broad-spectrum systemic antifungal agent with prophylactic activity in neutropenic patients, especially for those at high risk of prolonged neutropenia. PMID:10858349

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  7. Vertex potentials evoked by nociceptive laser stimulation of oral mucosa: relationship to stimulus intensity.

    PubMed

    Svensson, P; Arendt-Nielsen, L; Kaaber, S; Bjerring, P

    1993-01-01

    The present study investigated the relationship between stimulus intensity and size of vertex potentials (VPs) and methods for quantification of VPs elicited by nociceptive argon laser stimulation of the oral mucosa. VPs were evoked by warning and self-triggered stimulation of the tongue and hand. A significant increase was found in amplitude, power, and root-mean-square (RMS) values of the averaged VPs as the intensity of the laser stimuli increased. The latency of the major negative peak decreased significantly with increased stimulus intensity. The use of a warning light stimulus prior to the laser stimulus elicited a visually evoked vertex potential, which served as a control. The power and RMS values of the VPs elicited by warning stimulation of the tongue showed the largest increase and only a small variation when calculated in the 0.2 to 0.7 seconds time interval. PMID:8329904

  8. Persephin: A potential key component in human oral cancer progression through the RET receptor tyrosine kinase-mitogen-activated protein kinase signaling pathway.

    PubMed

    Baba, Takao; Sakamoto, Yosuke; Kasamatsu, Atsushi; Minakawa, Yasuyuki; Yokota, Satoshi; Higo, Morihiro; Yokoe, Hidetaka; Ogawara, Katsunori; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

    2015-08-01

    Persephin (PSPN) is a neurotrophic factor of the glial cell line-derived neurotrophic factor (GDNF) family that promotes survival of multiple populations of neurons. Little is known about the relevance of PSPN in human malignancy including oral squamous cell carcinoma (OSCC). This study was undertaken to evaluate PSPN mRNA and protein expression by analyzing cellular proliferation and the cell cycle in PSPN knockdown cells in vitro. PSPN mRNA and protein were significantly (P?oral keratinocytes (n?=?7). Cellular proliferation decreased significantly (P?potential for OSCC. PMID:24375483

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

    SciTech Connect

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

    2014-10-15

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

  10. Oral medicine and the ageing population.

    PubMed

    Yap, T; McCullough, M

    2015-03-01

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

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

    PubMed Central

    Bennett, Michael; Mashimo, Hiroshi

    2014-01-01

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

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

    SciTech Connect

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

    1994-12-31

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

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

    PubMed

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

    2016-03-01

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

  14. Investigation of the Enteric Pathogenic Potential of Oral Campylobacter concisus Strains Isolated from Patients with Inflammatory Bowel Disease

    PubMed Central

    Octavia, Sophie; Day, Andrew S.; Riordan, Stephen M.; Grimm, Michael C.; Lan, Ruiting; Lemberg, Daniel; Tran, Thi Anh Tuyet; Zhang, Li

    2012-01-01

    Background Campylobacter concisus, a bacterium colonizing the human oral cavity, has been shown to be associated with inflammatory bowel disease (IBD). This study investigated if patients with IBD are colonized with specific oral C. concisus strains that have potential to cause enteric diseases. Methodology Seventy oral and enteric C. concisus isolates obtained from eight patients with IBD and six controls were examined for housekeeping genes by multilocus sequence typing (MLST), Caco2 cell invasion by gentamicin-protection-assay, protein analysis by mass spectrometry and SDS-PAGE, and morphology by scanning electron microscopy. The whole genome sequenced C. concisus strain 13826 which was isolated from an individual with bloody diarrhea was included in MLST analysis. Principal Findings MLST analysis showed that 87.5% of individuals whose C. concisus belonged to Cluster I had inflammatory enteric diseases (six IBD and one with bloody diarrhea), which was significantly higher than that in the remaining individuals (28.6%) (P<0.05). Enteric invasive C. concisus (EICC) oral strain was detected in 50% of patients with IBD and none of the controls. All EICC strains were in Cluster 1. The C. concisus strain colonizing intestinal tissues of patient No. 1 was closely related to the oral C. concisus strain from patient No. 6 and had gene recombination with the patient’s own oral C. concisus. The oral and intestinal C. concisus strains of patient No. 3 were the same strain. Some individuals were colonized with multiple oral C. concisus strains that have undergone natural recombination. Conclusions This study provides the first evidence that patients with IBD are colonized with specific oral C. concisus strains, with some being EICC strains. C. concisus colonizing intestinal tissues of patients with IBD at least in some instances results from an endogenous colonization of the patient’s oral C. concisus and that C. concisus strains undergo natural recombination. PMID:22666490

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

    PubMed

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

    2014-10-15

    Most previous studies have linked cancer-macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression. PMID:25016285

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

    PubMed Central

    Burger-Calderon, Raquel; Webster-Cyriaque, Jennifer

    2015-01-01

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

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

    PubMed

    Burger-Calderon, Raquel; Webster-Cyriaque, Jennifer

    2015-01-01

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

  18. Estrogen receptor β promoter methylation: a potential indicator of malignant changes in breast cancer

    PubMed Central

    Gao, Lei; Qi, Xiaolong; Hu, Kaiwen; Zhu, Ruili; Xu, Wei; Sun, Shipeng; Zhang, Lixin; Yang, Ximing; Hua, Baojin

    2016-01-01

    Introduction Estrogen receptor β (ERβ) always lacks expression in estrogen-dependent tumors, which may result from gene inactivation by methylation. In this study, we aimed to determine whether aberrant methylation of the ERβ promoter is associated with decreased ERβ gene expression in breast cancer. Material and methods ERβ methylation status was determined for 132 pairs of breast cancer and adjacent normal tissues via the MethyLight method. Additionally, mRNA relative expression was quantified by real-time polymerase chain reaction (RT-PCR) to determine whether aberrant methylation had a negative correlation with expression. The correlation of ERβ promoter methylation and clinical parameters is also discussed. Results Methylation was observed in 96 (72.7%) breast cancer samples, and the median percentage of fully methylated reference (PMR) among methylated tissues was 0.83. Meanwhile, 94 (71.2%) adjacent normal tissues were methylated and the median PMR was 0.48. Compared to adjacent normal tissues, the methylation level of breast cancer was significantly higher (p < 0.001) and mRNA expression was much lower (p < 0.001). There was a significant correlation between ERβ methylation and mRNA expression in adjacent normal breast tissues (p = 0.004). In addition, the methylation rate of cancer tissues whose maximum diameter < 3 cm was significantly higher than those > 3 cm (p = 0.025). Conclusions ERβ promoter methylation level varies between cancerous and adjacent normal breast tissues. There was significant downregulation of ERβ methylation expression in pre-cancerous stages of breast cancer. Therefore, demethylation drugs may offer a potential strategy for preventing the development of pre-cancerous cells. PMID:26925128

  19. Work in progress: potential oral and intravenous paramagnetic NMR contrast agents

    SciTech Connect

    Runge, V.M.; Stewart, R.G.; Clanton, J.A.; Jones, M.M.; Lukehart, C.M.; Partain, C.L.; James, A.E. Jr.

    1983-06-01

    The potential use of paramagnetic compounds as nuclear magnetic resonance (NMR) contrast agents was examined in vitro. The T1 relaxation times for serial dilutions of Cu/sup 2 +/, Cr/sup 3 +/, Fe/sup 3 +/, and Mn/sup 2 +/ ions in saline, gadolinium oxalate (a potential oral contrast agent) in suspension, and chromium EDTA (a potential intravenous contrast agent) in solution were determined. The effect on T1 of increasing the concentration of oxygen in solution was also examined. The relative magnitude of the decrease in T1 was, as expected, proportional to both the concentration of the paramagnetic substance and its effective magnetic moment. Thus NMR has the potential to detect differences in tissue oxygenation. By incorporating paramagnetic metal ions into insoluble compounds or stable complexes, toxicity can be dramatically reduced while maintaining a significant paramagnetic effect. Highly insoluble paramagnetic compounds or stable paramagnetic ion complexes can thus be utilized as effective NMR contrast agents with significantly diminished toxicity.

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

    PubMed

    Lassen, Michael Rud; Laux, Volker

    2008-01-01

    In Western countries, venous thromboembolism (VTE) is a widespread and serious disorder, with hospital admission rates that appear to be increasing. Current anticoagulant therapies available for the prevention and treatment of VTE have several drawbacks that make them either difficult to manage effectively, due to a need for careful monitoring to control coagulation, or, in the case of parenterally administered agents, inconvenient for long-term use. To address some of these issues, new anticoagulants are in clinical development that can be orally administered and directly target specific factors in the coagulation cascade. This article reviews the rationale behind development of these novel agents and provides a critical appraisal of their clinical potential. In addition, the impact that the introduction of such agents into clinical practice would have is discussed from the patient perspective. PMID:19337550

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

    PubMed Central

    Lassen, Michael Rud; Laux, Volker

    2008-01-01

    In Western countries, venous thromboembolism (VTE) is a widespread and serious disorder, with hospital admission rates that appear to be increasing. Current anticoagulant therapies available for the prevention and treatment of VTE have several drawbacks that make them either difficult to manage effectively, due to a need for careful monitoring to control coagulation, or, in the case of parenterally administered agents, inconvenient for long-term use. To address some of these issues, new anticoagulants are in clinical development that can be orally administered and directly target specific factors in the coagulation cascade. This article reviews the rationale behind development of these novel agents and provides a critical appraisal of their clinical potential. In addition, the impact that the introduction of such agents into clinical practice would have is discussed from the patient perspective. PMID:19337550

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

    PubMed

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

    2012-04-01

    We evaluated in vitro the cariogenic and erosive potential of antitussive liquid oral medications for paediatric use. Fifteen paediatric liquid antitussives were sampled. The endogenous pH was evaluated by potentiometry, titratable acidity was measured according to the method adopted by the Association of Official Analytical Chemists, total soluble solids content (TSSC) readings were performed by Brix refractometry using the Abbé refractometer, and the total sugar content was determined according to the Fehling methodology. The experiments were performed in triplicate and the obtained data were entered in the Excel software, analyzed and presented by descriptive statistics (means and standard deviations). Endogenous pH values ranged from 2.49 ± 0.09 (Iodetox®) to 6.75 ± 0.005 (Carbocysteine®) and twelve medications showed pHs below the critical value of 5.5 for enamel demineralization. Iodetox® (0.021 ± 0.01) presented the lowest titratable acidity and Aerofrin® (1.171 ± 0.01) presented the highest titratable acidity. Celergin® presented the highest TSSC (62.26 ± 0.40) and Acetyleysteine® (100 mg granules bags) presented the lowest TSSC (3.25 ± 0.43). Only 5 medications contained sugar, with total sugar content ranging from 35.93% ± 6.65 (Iodetox®) to 59.60% DP ± 6.66 (Celergin®). The paediatric antitussive medications showed low endogenous pH, some of them even below the critical value for enamel dissolution (pH<5.5). These antitussives are potentially cariogenic and erosive to dental structures if used frequently because of the high titratable acidity and high sugar concentration, especially when adequate oral clearance is not performed after administration of each dose. PMID:26591735

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

    PubMed

    Matayoshi, Sen; Chiba, Shunmei; Lin, Yanfui; Arakaki, Kazunari; Matsumoto, Hirofumi; Nakanishi, Takaya; Suzuki, Mikio; Kato, Seiya

    2013-05-01

    Head and neck squamous cell carcinoma (HNSCC) is the sixth most common non-skin cancer worldwide. Despite improvement in therapeutic strategies, the prognosis of advanced HNSCC remains poor. The extacellular lipid mediators known as lysophosphatidic acids (LPAs) have been implicated in tumorigenesis of HNSCC. LPAs activate G-protein-coupled receptors not only in the endothelial differentiation gene (Edg) family (LPA1, LPA2, LPA3) but also in the phylogenetically distant non-Edg family (LPA4, LPA5, LPA6). The distinct roles of these receptor isoforms in HNSCC tumorigenesis have not been clarified. In the present study, we investigated the effect of ectopic expression of LPA4 in SQ-20B, an HNSCC cell line, expressing a trivial level of endogenous LPA4. LPA (18:1) stimulated proliferation of SQ-20B cells, but did not affect proliferation of HEp-2, an SCC cell line expressing higher levels of LPA4, comparable to those of with LPA1. LPA-stimulated proliferation of SQ-20B cells was attenuated by Ki16425 and Rac1 inhibitor, but not by Y-27632. Infection with doxycycline-regulatable adenovirus vector expressing green fluorescent protein-tagged LPA4 (AdvLPA4G) abolished LPA-stimulated proliferation in SQ-20B cells with the accumulation of G2/M-phasic cells. Ectopic LPA4 induction further downregulated proliferation of Ki16425-treated SQ-20B cells, of which downregulation was partially recovered by LPA. Ectopic LPA4 induction also downregulated proliferation of Rac1 inhibitor-treated SQ-20B cells, however, LPA no longer recovered it. Finally, LPA-induced cell motility was suppressed by ectopic LPA4 expression as well as by Ki16425, Rac1 inhibitor or Y-27632. Our data suggest that LPA4 signaling potentially modulates malignant behavior of SQ-20B cells. LPA signaling, which is mediated by both Edg and non-Edg receptors, may be a determinant of malignant behavior of HNSCC and could therefore be a promising therapeutic target. PMID:23467751

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

    PubMed Central

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

    2013-01-01

    Head and neck squamous cell carcinoma (HNSCC) is the sixth most common non-skin cancer worldwide. Despite improvement in therapeutic strategies, the prognosis of advanced HNSCC remains poor. The extacellular lipid mediators known as lysophosphatidic acids (LPAs) have been implicated in tumorigenesis of HNSCC. LPAs activate G-protein-coupled receptors not only in the endothelial differentiation gene (Edg) family (LPA1, LPA2, LPA3) but also in the phylogenetically distant non-Edg family (LPA4, LPA5, LPA6). The distinct roles of these receptor isoforms in HNSCC tumorigenesis have not been clarified. In the present study, we investigated the effect of ectopic expression of LPA4 in SQ-20B, an HNSCC cell line, expressing a trivial level of endogenous LPA4. LPA (18:1) stimulated proliferation of SQ-20B cells, but did not affect proliferation of HEp-2, an SCC cell line expressing higher levels of LPA4, comparable to those of with LPA1. LPA-stimulated proliferation of SQ-20B cells was attenuated by Ki16425 and Rac1 inhibitor, but not by Y-27632. Infection with doxycycline-regulatable adenovirus vector expressing green fluorescent protein-tagged LPA4 (AdvLPA4G) abolished LPA-stimulated proliferation in SQ-20B cells with the accumulation of G2/M-phasic cells. Ectopic LPA4 induction further downregulated proliferation of Ki16425-treated SQ-20B cells, of which downregulation was partially recovered by LPA. Ectopic LPA4 induction also downregulated proliferation of Rac1 inhibitor-treated SQ-20B cells, however, LPA no longer recovered it. Finally, LPA-induced cell motility was suppressed by ectopic LPA4 expression as well as by Ki16425, Rac1 inhibitor or Y-27632. Our data suggest that LPA4 signaling potentially modulates malignant behavior of SQ-20B cells. LPA signaling, which is mediated by both Edg and non-Edg receptors, may be a determinant of malignant behavior of HNSCC and could therefore be a promising therapeutic target. PMID:23467751

  5. Assessment of Malignant Potential in Intraductal Papillary Mucinous Neoplasms of the Pancreas: Comparison between Multidetector CT and MR Imaging with MR Cholangiopancreatography.

    PubMed

    Kang, Hyo-Jin; Lee, Jeong Min; Joo, Ijin; Hur, Bo Yun; Jeon, Ju Hyeon; Jang, Jin-Young; Lee, Kyoungbun; Ryu, Ji Kon; Han, Joon Koo; Choi, Byung Ihn

    2016-04-01

    Purpose To compare the diagnostic performance of multidetector computed tomography (CT) and magnetic resonance (MR) imaging with MR cholangiopancreatography (MRCP) in identifying the malignant potential of pancreatic intraductal papillary neoplasms (IPMNs) and evaluate their intermodality agreement. Materials and Methods Institutional review board approval was obtained, and the requirement for informed consent was waived for this retrospective study. In 129 patients with pathologically proved pancreatic IPMNs, three reviewers independently evaluated their preoperative CT and MR imaging with MRCP findings. Intermodality agreement between multidetector CT and MR imaging with MRCP, as well as interobserver agreement of each imaging modality, for depicting high-risk stigmata and worrisome features were assessed. Diagnostic values of other signs of overt malignancy, including the presence of a parenchymal mass and local-regional extension, were analyzed. Diagnostic performance and intermodality agreement were assessed by using receiver operating characteristics (ROC) curve analysis and weighted κ statistics. Results Overall, multidetector CT and MR imaging with MRCP were similar in their ability to depict signs suspicious or indicative of malignancy in patients with IPMN (area under the ROC curve [AUC] = 0.82 for both), with good intermodality agreement (κ = 0.75) and moderate interobserver agreement (κ = 0.47-0.59) when high-grade dysplasia was used as the cutoff for malignancy. When parenchymal masses and local-regional extensions were also considered as overt signs of malignancy, the ability to identify invasive IPMNs significantly increased (AUC = 0.87 for CT and AUC = 0.88 for MR imaging), with high sensitivity (94.3%), while maintaining specificity (69.1%). Conclusion The diagnostic performance of multidetector CT and MR imaging with MRCP for identifying the malignant potential of pancreatic IPMNs was similar and showed good intermodality agreement, suggesting that follow-up with either modality may be used. (©) RSNA, 2015 Online supplemental material is available for this article. PMID:26517448

  6. Zinc as a potential enteroprotector in oral rehydration solutions: its role in nitric oxide metabolism.

    PubMed

    Wingertzahn, Mark A; Rehman, Khalil U; Altaf, Waseem; Wapnir, Raul A

    2003-03-01

    Zinc has been recognized as an antioxidant with potential for chronic and acute effects. Oxidative damage produced by free radicals, including nitric oxide (NO), is responsible for certain types of intestinal malabsorption syndromes and diarrhea. Under physiologic or mildly stimulatory conditions for NO synthesis, the small intestine characteristically is in a proabsorptive state; however, an excessive production of NO triggers formation of cyclic nucleotides, which cause secretion and malabsorption. In this study, we hypothesized that low-molecular-weight, soluble zinc chelates could modulate the effects of induced NO excess on the small intestine. In vitro experiments demonstrated that zinc-citrate or zinc-histidine at > or =0.66 mM, as well as a known NO scavenger, 2-[carboxyphenyl]-4,4,4,4-tetramethylimidazoline-1-oxyl-3-oxide, at 2 microM, were effective at removing chemically generated NO. In vivo jejunal perfusions, conducted in healthy rats under anesthesia, showed that c-PTIO reduced the proabsorptive effects produced by 1 mM L-arginine, the precursor of NO. In a standard oral rehydration solution, 1 mM zinc-citrate partially reversed the antiabsorptive effects on potassium caused by an excess of NO generated from 20 mM L-arginine but did not alter sodium or water absorption. The data are consistent with the view that soluble zinc compounds incorporated into an oral rehydration solution may deserve further attention as a means to scavenge NO with fluids used for the treatment of chronic or acute diarrhea, especially in malnourished children who are often zinc deficient. PMID:12595591

  7. Pseudoepitheliomatous Hyperplasia: Relevance in Oral Pathology

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2009-01-01

    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

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

    PubMed

    Tong, Zhongchun; Ni, Longxing; Ling, Junqi

    2014-10-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  12. Malignant hypertension

    MedlinePLUS

    ... hypertension; Arteriolar nephrosclerosis; Nephrosclerosis - arteriolar; Hypertension - malignant; High blood pressure - malignant ... affects a small number of people with high blood pressure, including children and adults. It is more common ...

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

    PubMed Central

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

    2014-01-01

    In India, oral cancer has consistently ranked among top three causes of cancer-related deaths, and it has emerged as a top cause for the cancer-related deaths among men. Lack of effective therapeutic options is one of the main challenges in clinical management of oral cancer patients. We interrogated large pool of samples from oral cancer gene expression studies to identify potential therapeutic targets that are involved in multiple cancer hallmark events. Therapeutic strategies directed towards such targets can be expected to effectively control cancer cells. Datasets from different gene expression studies were integrated by removing batch-effects and was used for downstream analyses, including differential expression analysis. Dependency network analysis was done to identify genes that undergo marked topological changes in oral cancer samples when compared with control samples. Causal reasoning analysis was carried out to identify significant hypotheses, which can explain gene expression profiles observed in oral cancer samples. Text-mining based approach was used to detect cancer hallmarks associated with genes significantly expressed in oral cancer. In all, 2365 genes were detected to be differentially expressed genes, which includes some of the highly differentially expressed genes like matrix metalloproteinases (MMP-1/3/10/13), chemokine (C-X-C motif) ligands (IL8, CXCL-10/-11), PTHLH, SERPINE1, NELL2, S100A7A, MAL, CRNN, TGM3, CLCA4, keratins (KRT-3/4/13/76/78), SERPINB11 and serine peptidase inhibitors (SPINK-5/7). XIST, TCEAL2, NRAS and FGFR2 are some of the important genes detected by dependency and causal network analysis. Literature mining analysis annotated 1014 genes, out of which 841 genes were statistically significantly annotated. The integration of output of various analyses, resulted in the list of potential therapeutic targets for oral cancer, which included targets such as ADM, TP53, EGFR, LYN, CTLA4, SKIL, CTGF and CD70. PMID:25029526

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

    PubMed Central

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

    2013-01-01

    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

  15. Peritoneal washing cytologic analysis of ovarian serous tumors of low malignant potential to detect peritoneal implants and predict clinical outcome

    PubMed Central

    Sneige, Nour; Thomison, John B.; Malpica, Anais; Gong, Yun; Ensor, Joe; Silva, Elvio G.

    2013-01-01

    Background Patients with ovarian serous tumors of low malignant potential (OSLMP) who have peritoneal implants, especially invasive implants, are at increased risk of developing tumor recurrence. The ability of peritoneal washing (PW) cytology, to detect the presence and type of peritoneal implants has not been adequately investigated, and its prognostic significance is unknown. Methods We retrospectively reviewed records and PW specimens of 101 patients diagnosed with and treated for OSLMP between 1996 and 2010 at The University of Texas MD Anderson Cancer Center. We compared patients’ staging biopsy findings with those of our review of the PWs. Follow-up data were also analyzed. Results Of the 96 patients with staging biopsy results available, 26 (27%) had peritoneal implants (17 noninvasive, 9 invasive), 19 (20%) had endosalpingiosis, and 51 (53%) had negative findings. The PW specimens of 18 of the 26 patients (69%) with peritoneal implants were positive for serous neoplasm, and a correlation was found between cytologic and histologic findings (p < 0.0001). The sensitivity, specificity, positive predictive, and negative predictive values were 69%, 84%, 62% and 88%, respectively. Four of 101 patients had disease recurrence, 3 of these patients had invasive implants and 1 patient had noninvasive implants. None of the patients who had negative staging biopsy findings or endosalpingiosis but PW specimens positive for serous neoplasm developed disease recurrence. Conclusions PW cytology detects the presence of peritoneal implants with moderate accuracy. Long-term studies are needed to determine whether positive PW cytologic findings are an independent predictor of tumor recurrence. PMID:22826172

  16. Molecular genetic evidence of an independent origin of serous low malignant potential implants and lymph node inclusions.

    PubMed

    Emerson, Robert E; Wang, Mingsheng; Liu, Fang; Lawrence, W Dwayne; Abdul-Karim, Fadi W; Cheng, Liang

    2007-10-01

    Patients with ovarian serous tumors of low malignant potential (LMP) are commonly found to have peritoneal implants. Less commonly, similar lesions are seen in lymph nodes, sometimes in association with endosalpingiosis. We compared these lesions to the coexisting ovarian LMP tumors to determine whether they are clonally related to the ovarian neoplasm. Seventeen patients with serous LMP tumors present at 2 or more sites were identified. Tissue samples were microdissected from formalin-fixed paraffin-embedded tissue blocks. Samples of normal tissue, the ovarian LMP tumors, peritoneal LMP implants, and LMP inclusions within lymph nodes were obtained. Genomic DNA was extracted from the samples, and polymerase chain reaction and X-chromosome inactivation (human androgen receptor assay) analysis were performed. The pattern of X-chromosome inactivation could be determined in 15 of the 17 cases, and nonrandom X-chromosome inactivation was observed in 13 of these cases. Twelve of these cases included both ovarian and extraovarian LMP tumors. In 9 of these 12 cases, the extraovarian LMP tumor shared a similar pattern of nonrandom X-chromosome inactivation with the ovarian tumor. In these cases, the shared inactivation pattern was seen at 1 extraovarian site (3 cases), 2 extraovarian sites (4 cases), 5 extraovarian sites (1 case), and 7 of 8 extraovarian sites (1 case). In the remaining 3 cases, opposite patterns of nonrandom X-chromosome inactivation were seen. These data suggest that, in most cases, serous LMP tumor implants and lymph node inclusions share a common clonal origin with the associated ovarian tumors. However, in at least some cases, the implants and inclusions seem to arise independently from the associated ovarian serous LMP tumors. PMID:17885488

  17. 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 ...

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

    PubMed

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

    2014-12-01

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

  19. Areca nut and its role in oral submucous fibrosis

    PubMed Central

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

    Blake, Christopher

    2009-01-01

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

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

    ERIC Educational Resources Information Center

    Blake, Christopher

    2009-01-01

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

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

    PubMed

    Sharma, Akhilesh

    2012-01-01

    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

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

    PubMed

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

    2012-03-01

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

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

    PubMed

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

    2016-02-15

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

  5. Malignancy-associated pruritus.

    PubMed

    Rowe, B; Yosipovitch, G

    2016-01-01

    Malignancy-associated pruritus can be the result of a neoplasm's local effect on tissue or due to the systemic reaction to malignancy. A systemic reaction to malignancy has been termed 'paraneoplastic itch' and can be the first sign of an underlying malignancy. Paraneoplastic itch is most commonly caused by lymphoproliferative malignancies, and severity of itch correlates with stage of disease in Hodgkin's lymphoma and polycythemia vera. Non-melanoma skin cancer is the most common type of malignancy-associated pruritus, and recent data indicate that pruritus is associated with more than one-third of non-melanoma skin cancers. Cutaneous T-cell lymphomas (CTCL), particularly more advanced stages, cause intractable pruritus and recent investigations into the pathophysiology of CTCL-associated itch have implicated cyotokine interleukin-31 as a putative mediator. Treatments that reduce itch in CTCL patients, such as histone deacetylase inhibitors (HDACi), Mogamulizumab, a novel monoclonal antibody against chemokine receptor type-4, and oral corticosteroids, have demonstrated a correlation between their anti-pruritic effect and reduced serum levels of interleukin-31. PMID:26416212

  6. Immunohistochemical Profile of Uterine Leiomyoma With Bizarre Nuclei; Comparison With Conventional Leiomyoma, Smooth Muscle Tumors of Uncertain Malignant Potential and Leiomyosarcoma

    PubMed Central

    Dastranj Tabrizi, Ali; Ghojazadeh, Morteza; Thagizadeh Anvar, Hanieh; Vahedi, Amir; Naji, Siamak; Mostafidi, Elmira; Berenjian, Siamak

    2015-01-01

    Purpose: To assess the immunohistochemical profile of the atypical nuclei in leiomyoma with bizarre nuclei and compare with benign and malignant counterparts. Methods: 26 cases of uterine smooth muscle tumors including 12 leiomyosarcoma(LMS), 10 leiomyoma with bizarre nuclei (LBN) and 4 smooth muscle tumor with uncertain malignant potential (STUMP) were selected using whole tissue sections for this study and analysis. Six cases of ordinary leiomyoma were included as benign control group. All representative section were stained for P53, Ki67, estrogen receptor and progestrone receptor. Analysis was carried out using SPSS 16.0 for windows software. Results: Six out of 12 cases of LMS showed strong and diffuse nuclear staining with p53 antibody (50%). In contrast none of STUMPs and only one case of LBN cases showed focal positive reaction with P53. Percentage of positive cells for ki67 in LMS was 14.92 while only 0.85% of cells in LBNs was labeled with Ki67 proliferative marker. (P<0.001). Regarding steroid hormone receptors a significant loosing trend was found in these receptors from benign toward malignant tumors through LBN and STUMP cases. Conclusion: Loss of inhibitory function of wild type P53 gene in leiomyosarcoma is an essential event that discriminate frankly malignant tumors from STUMP and atypical leiomyoma. PMID:26793616

  7. Podoplanin--a novel marker in oral carcinogenesis.

    PubMed

    Swain, Niharika; Kumar, Shwetha V; Routray, Samapika; Pathak, Jigna; Patel, Shilpa

    2014-09-01

    Podoplanin, a transmembrane sialoglycoprotein, is a specific marker for lymphatic endothelial cells which in recent years has gained prominent notoriety for its role in tumor progression and metastasis. It is an extensively studied biomarker for predictive assessment of malignant transformation as well as biologic behavior in both human precancer and cancer, respectively. This review summarizes the association of podoplanin overexpression in oral potentially malignant disorders and oral cancer with special emphasis on its putative role in carcinogenesis as well as its prospective use in targeted therapy. PMID:24964963

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

    PubMed Central

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

    2014-01-01

    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

  9. Evaluation of potential salivary acetaldehyde production from ethanol in oral cancer patients and healthy subjects

    PubMed Central

    Kocaelli, H; Apaydin, A; Aydil, B; Ayhan, M; Karadeniz, A; Ozel, S; Y?lmaz, E; Akgün, B; Eren, B

    2014-01-01

    Background: Acetaldehyde has been implicated as a major factor in oral carcinogenesis associated with alcohol consumption. In this study, saliva samples from oral cancer patients and healthy individuals were incubated in vitro with ethanol in order to investigate factors which can influence salivary acetaldehyde production. Materials and Methods: A total of 66 individuals (40 males and 26 females, mean age 52 years) participated in the study. Participants were classified into three groups: Group 1 (oral cancer patients [n = 20]); Group 2 (poor dental health status [n = 25]) and Group 3 (good dental health status [n=21]). Every patient chewed a 1g piece of paraffin chewing gum for 1 minute then saliva samples were collected from all individuals. After in vitro incubation of the samples with ethanol, the levels of salivary acetaldehyde production was measured by head space gas chromatography. Kruskal-Wallis and Mann-Whitney tests and Spearman's Correlations analysis were performed for statistical analyses. Results: The salivary acetaldehyde production was significantly higher (p <0.0001) in both group 1 and group 2 when compared to group 3. However, there was no significant difference between group 1 and group 2. Poor dental health status, infrequent oral hygiene habits and dental visits, smoking and presence of a dental prosthesis were significant parameters for increased levels of salivary acetaldehyde production from alcohol. The evaluation of salivary acetaldehyde production after in vitro incubation with ethanol may be useful for early detection of oral cancer. Conclusion: According to the results of this study, the significantly higher levels of salivary acetaldehyde production in oral cancer patients and individuals with poor dental health status may suggest a possible link between increased salivary acetaldehyde production and oral cancer. Improved oral hygiene can effectively decrease the level of salivary acetaldehyde production in oral cavity. Hippokratia 2014; 18 (3): 269-274. PMID:25694764

  10. 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...

  11. The oral route as a potential way of transmission of Schistosoma bovis in goats.

    PubMed

    Boulanger, D; Schneider, D; Sidikou, F; Capron, A; Chippaux, J P; Sellin, B

    1999-06-01

    The infectivity of Schistosoma bovis cercariae administered orally was evaluated in Sahelian goats. Compared to the percutaneous route, a single massive oral dose resulted in a worm burden and in fecal egg excretion reduced by one-half. Surprisingly, tissue egg counts were increased by more than 4-fold. Fecundity of individual female schistosomes was, therefore, markedly increased. When infective doses were administered weekly for 20 wk, both worm and egg burdens were doubled without modification of the individual worm pair fecundity. Repeated oral infections seem to have induced an acquired tolerance toward parasite antigens. These results confirm the epidemiologic relevance of the oral route in a host species inclined to become infected through drinking water rather than percutaneous exposures. PMID:10386438

  12. Review of a potential role for zinc supplementation in oral rehydration solutions.

    PubMed

    Matarese, Laura E; Steiger, Ezra; Seidner, Douglas L

    2003-06-01

    Patients with short bowel syndrome often present with diarrhea and significant fluid and electrolyte abnormalities. Management consists of the use of medication, dietary modification, and oral rehydration solutions. Zinc deficiency has been shown to result in diarrhea. Oral zinc has been used for the management of acute diarrhea primarily in underprivileged children in developing countries. The effectiveness and feasibility of adding zinc to oral rehydration solutions (ORS) to abate and control diarrhea for adult patients with intestinal failure caused by short bowel syndrome has not been studied. Based on studies evaluating the use of oral zinc supplementation in the treatment of acute diarrhea, recommendations are made for the composition of ORS in adults. PMID:16215043

  13. Lymph node involvement in ovarian serous tumors of low malignant potential (borderline tumors): pathology, prognosis, and proposed classification.

    PubMed

    McKenney, Jesse K; Balzer, Bonnie L; Longacre, Teri A

    2006-05-01

    The occurrence of regional lymph node involvement (LNI) in patients with primary ovarian serous tumors of low malignant potential (S-LMP), although well described in the literature, continues to be problematic. Most studies indicate that LNI is not associated with an adverse prognosis, but there has not been a comprehensive study addressing the histologic patterns of LNI, the importance, if any, of classifying the type of LNI (ie, as either noninvasive or invasive in analogy to peritoneal implant classification), or the presence and significance of associated endosalpingiosis. To further evaluate LNI in S-LMP, 74 patients with ovarian S-LMP and a lymph node biopsy or sampling were studied. Thirty-one of 74 patients had LNI in pelvic (18; 58%), mesenteric/omental (9; 29%), paraaortic (8; 26%), or supradiaphragmatic (2; 6%) lymph nodes. The number of involved nodes ranged from 1 to 20 (mean, 11.1). Four patterns of LNI were identified: individual cells, clusters of cells, and simple, nonbranching papillae (28 of 31; 90%); intraglandular (21 of 31; 68%); cells with prominent cytoplasmic eosinophilia ("eosinophilic cell" pattern) (16 of 31; 52%); and micropapillary pattern (5 of 31; 16%). LNI was diffuse in at least one lymph node in 13 patients (42%) and formed nodular aggregates greater than 1 mm in 6 patients (19%). Nodal endosalpingiosis was present in 58% of cases with LNI compared with 35% without LNI (P=0.06). There was no significant difference in survival for patients with LNI compared with patients without LNI. However, the presence of discrete nodular aggregates of epithelium greater than 1 mm in linear dimension without intervening lymphoid tissue was associated with a statistically significant decreased disease-free survival when compared with other patterns of LNI (P=0.02). Nodular aggregates were strongly associated with desmoplastic fibrous stromal reaction (P=0.001) and micropapillary architecture (0.02). There was also a trend for decreased survival among patients with LNI without associated endosalpingiosis (56%) compared with patients with LNI associated with endosalpingiosis (85%) and those with endosalpingiosis only (93%). This study suggests that patients with ovarian S-LMP may be further substratified into risk categories by the presence of nodular aggregates of S-LMP in lymph nodes, a feature that is more common in cases with micropapillary architecture and associated stromal reaction in the intranodal tumor. This high risk pattern of LNI may have a predictive value similar to invasive peritoneal implants and deserves independent evaluation in future studies of S-LMP. PMID:16699316

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

    SciTech Connect

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

    2014-05-09

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

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

    PubMed Central

    Decorte, Inge; Steensels, Mieke; Lambrecht, Bénédicte

    2015-01-01

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

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

    PubMed

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

    2016-01-01

    The potential of immobilized artificial membrane (IAM) chromatography to estimate human oral absorption (%HOA) was investigated. For this purpose, retention indices on IAM stationary phases reported previously by our group or measured by other authors under similar conditions were used to model %HOA data, compiled from literature sources. Considering the pH gradient in gastrointestinal tract, the highest logkw(IAM) values were considered, obtained either at pH7.4 or 5.5, defined as logkw(IAM)(best). Non linear models were established upon introduction of additional parameters and after exclusion of drugs which are substrates either to efflux or uptake transporters. The best model included Abraham's hydrogen-bond acidity parameter, molecular weight as well as the positively and negatively charged molecular fractions. For reasons of comparison between IAM chromatography and traditional lipophilicity, corresponding models were derived by replacing IAM retention factors with octanol-water distribution coefficients (logD). An overexpression of electrostatic interactions with phosphate anions was observed in the case of IAM retention as expressed by the negative contribution of the positively charged fraction F(+). The same parameter is statistically significant also in the logD model, but with a positive sign, indicating the attraction of basic drugs in the negatively charged inner membrane. To validate the obtained models a blind test set of 22 structurally diverse drugs was used, whose logkw(IAM)(best) values were determined and analyzed in the present study under similar conditions. IAM retention factors were further compared with MDCK cell lines permeability data taken from literature for a set of validation drugs. The overexpression of electrostatic interactions with phosphate anions on IAM surface was also evident in respect to MDCK permeability. In contrast to the clear classification between drugs with high and poor (or intermediate) absorption provided by MDCK permeability, %HOA plotted versus both IAM and logD data result in a saturation curve with a smoother ascending line. PMID:26485055

  17. Potential for bias in case-control studies of oral contraceptives and breast cancer.

    PubMed

    Skegg, D C

    1988-02-01

    The discrepancies between the findings of the 6 large case-control studies to study the association between oral contraceptive (OC) use and breast cancer diagnosed in the 1980s may be due to chance or bias. The likelihood that chance played a role is suggested by the large numbers of subgroups examined in each study, the inconsistencies in the findings of different studies, and the wide confidence intervals around most of the relative risks. The most serious potential problem in case-control studies is that the procedures used to select cases and controls may produce groups that are not truly comparable. Recall bias is likely to contaminate information about the duration and type of part OC use. In addition, the more frequent examination of the breasts of women using OCs can produce surveillance bias. 6 procedures are recommended to minimize bias in future case-control studies of OC use and breast cancer: 1) whenever possible, cases and controls should be selected from an entire community; 2) if hospital controls need to be used, there should be explicit criteria for selecting them and the proportions of OC users in each diagnostic group should be presented; 3) women interviewed should not be aware of the study's hypotheses; 4) interviewers should be kept blind as to whether a subject is a case or control; 5) the possibility of recall bias should be investigated by comparing contraceptive histories from a sample of cases and controls with an independent source of information (preferably recorded before cancers were diagnosed); and 7) the interview should include questions about the frequency of breast examinations, so that any effects of more frequent surveillance of OC users can be controlled for. PMID:3276164

  18. Investigation of the potential of Raman spectroscopy for oral cancer detection in surgical margins.

    PubMed

    Cals, Froukje L J; Bakker Schut, Tom C; Hardillo, José A; Baatenburg de Jong, Robert J; Koljenovi?, Senada; Puppels, Gerwin J

    2015-10-01

    The poor prognosis of oral cavity squamous cell carcinoma (OCSCC) patients is associated with residual tumor after surgery. Raman spectroscopy has the potential to provide an objective intra-operative evaluation of the surgical margins. Our aim was to understand the discriminatory basis of Raman spectroscopy at a histological level. In total, 127 pseudo-color Raman images were generated from unstained thin tissue sections of 25 samples (11 OCSCC and 14 healthy) of 10 patients. These images were clearly linked to the histopathological evaluation of the same sections after hematoxylin and eosin-staining. In this way, Raman spectra were annotated as OCSCC or as a surrounding healthy tissue structure (i.e., squamous epithelium, connective tissue (CT), adipose tissue, muscle, gland, or nerve). These annotated spectra were used as input for linear discriminant analysis (LDA) models to discriminate between OCSCC spectra and healthy tissue spectra. A database was acquired with 88 spectra of OCSCC and 632 spectra of healthy tissue. The LDA models could distinguish OCSCC spectra from the spectra of adipose tissue, nerve, muscle, gland, CT, and squamous epithelium in 100%, 100%, 97%, 94%, 93%, and 75% of the cases, respectively. More specifically, the structures that were most often confused with OCSCC were dysplastic epithelium, basal layers of epithelium, inflammation- and capillary-rich CT, and connective and glandular tissue close to OCSCC. Our study shows how well Raman spectroscopy enables discrimination between OCSCC and surrounding healthy tissue structures. This knowledge supports the development of robust and reliable classification algorithms for future implementation of Raman spectroscopy in clinical practice. PMID:26237270

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2000-01-01

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

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

    PubMed

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

    2004-04-01

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

  2. Sensations and trigeminal somatosensory-evoked potentials elicited by electrical stimulation of endosseous oral implants in humans.

    PubMed

    Van Loven, K; Jacobs, R; Swinnen, A; Van Huffel, S; Van Hees, J; van Steenberghe, D

    2000-12-01

    The perception of bipolar electrical stimuli through implants was studied. The stimuli were delivered to permucosal oral endosseous implants in 15 individuals, who then reported tapping to beating sensations. In 10 out of the 15, these stimuli evoked clearly distinguishable potentials in the averaged electroencephalograms. The most prominent scalp potential was a positive wave with a latency between 18 and 25 ms, often preceded by a negative wave with a latency around 12-17 ms. In contrast, when a motor response was elicited by stimulation of the lip, a shorter latency wave around 8-11 ms was found additionally, indicating that the former-mentioned waves represent a true sensory response and not an artefact of myogenous origin. Furthermore, topical anaesthesia of the gingiva surrounding the implants in six individuals had little effect on the sensory responses. This evidence excluded peri-implant mucosal innervation as the origin of the perception and of the somatosensory-evoked waves elicited by the electrical stimulation of the oral implants. To the best of our knowledge, for the first time a sensation (osseoperception) has been elicited by electrical stimulation of endosseous oral implants and correlated with simultaneously recorded trigeminal somatosensory-evoked potentials (TSEPs). PMID:11084148

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

    PubMed

    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

    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

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

    PubMed Central

    Sales, Katiuchia Uzzun; Friis, Stine; Konkel, Joanne E.; Godiksen, Sine; Hatakeyama, Marcia; Hansen, Karina K.; Rogatto, Silvia Regina; Szabo, Roman; Vogel, Lotte K.; Chen, Wanjun; Gutkind, J. Silvio; Bugge, Thomas H.

    2014-01-01

    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 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

  5. Epigenetics in the hematologic malignancies

    PubMed Central

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

    2014-01-01

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

  6. Epigenetic down-regulation of integrin ?7 increases migratory potential and confers poor prognosis in malignant pleural mesothelioma.

    PubMed

    Laszlo, Viktoria; Hoda, Mir Alireza; Garay, Tamas; Pirker, Christine; Ghanim, Bahil; Klikovits, Thomas; Dong, Yawen W; Rozsas, Anita; Kenessey, Istvan; Szirtes, Ildiko; Grusch, Michael; Jakopovic, Marko; Samarzija, Miroslav; Brcic, Luka; Kern, Izidor; Rozman, Ales; Popper, Helmut; Zöchbauer-Müller, Sabine; Heller, Gerwin; Altenberger, Corinna; Ziegler, Barbara; Klepetko, Walter; Berger, Walter; Dome, Balazs; Hegedus, Balazs

    2015-10-01

    Malignant pleural mesothelioma (MPM) is a devastating malignancy characterized by invasive growth and rapid recurrence. The identification and inhibition of molecular components leading to this migratory and invasive phenotype are thus essential. Accordingly, a genome-wide expression array analysis was performed on MPM cell lines and a set of 139 genes was identified as differentially expressed in cells with high versus low migratory activity. Reduced expression of the novel tumour suppressor integrin ?7 (ITGA7) was found in highly motile cells. A significant negative correlation was observed between ITGA7 transcript levels and average displacement of cells. Forced overexpression of ITGA7 in MPM cells with low endogenous ITGA7 expression inhibited cell motility, providing direct evidence for the regulatory role of ITGA7 in MPM cell migration. MPM cells showed decreased ITGA7 expressions at both transcription and protein levels when compared to non-malignant mesothelial cells. The majority of MPM cell cultures displayed hypermethylation of the ITGA7 promoter when compared to mesothelial cultures. A statistically significant negative correlation between ITGA7 methylation and ITGA7 expression was also observed in MPM cells. While normal human pleura samples unambiguously expressed ITGA7, a varying level of expression was found in a panel of 200 human MPM samples. In multivariate analysis, ITGA7 expression was found to be an independent prognostic factor. Although there was no correlation between histological subtypes and ITGA7 expression, importantly, patients with high tumour cell ITGA7 expression had an increased median overall survival compared to the low- or no-expression groups (463 versus 278 days). In conclusion, our data suggest that ITGA7 is an epigenetically regulated tumour suppressor gene and a prognostic factor in human MPM. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26011651

  7. Role of tissue eosinophils in oral Leukoplakia: A pilot study

    PubMed Central

    Madhura, MG; Gajalakshmi, S; Kumar, B Veerendra; Suma, S; Sarita, Y; Shweta, RD

    2015-01-01

    Context: Tissue eosinophilia in oral squamous cell carcinoma has been well - recognized. Studies have reported both favorable and unfavorable prognoses associated with tissue eosinophils in oral squamous cell carcinoma. However, the role of eosinophils in the development of tumor is still unclear. Aims: The present study was an attempt to elucidate the potential role of tissue eosinophils in oral leukoplakia, a potentially malignant lesion. Settings and Design: To count eosinophils in tissues of normal subjects and oral leukoplakia cases. To compare tissue eosinophil count (TEC) between normal and oral leukoplakia cases. To compare TEC between dysplastic and non-dysplastic cases of oral leukoplakia and to correlate with degree of epithelial dysplasia. Materials and Methods: A total of 85 cases (59 cases of oral leukoplakia and 26 normal oral tissues) constituted the study material. Tissue eosinophils were counted in 10 different high- power fields. Statistical Analysis Used: Non-parametric tests (Mann-Whitney U-test, Kruskal-Wallis test, Mann-Whitney post hoc analysis and Spearman's correlation statistics). Results: Mean eosinophil count (MEC) in oral leukoplakia cases was significantly more when compared to normal subjects. MEC in dysplastic cases of oral leukoplakia was significantly more when compared to those without epithelial dysplasia (Mann-Whitney U-test). Furthermore, MEC was directly proportional to the degree of epithelial dysplasia (Spearman's correlation statistics). Conclusions: TEC may be used as an adjunct to predict the malignant transformation of dysplastic cases of oral leukoplakia. Eosinophilic infiltration in oral dysplastic cases should prompt a thorough evaluation for invasiveness, especially when features of invasion are absent or suspected in smaller biopsy specimens. Use of TEC as a prognostic indicator demands larger sample size and mandates long-term follow-up. PMID:26980954

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

    PubMed Central

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

    2012-01-01

    In pediatric patients with malignancy and those receiving hematopoietic stem cell transplants, bacterial and fungal infections have been the focus of fever and neutropenia episodes for decades. However, improved diagnostic capabilities have revealed viral pathogens as a significant cause of morbidity and mortality. Because of limited effective antiviral therapies, prevention of viral infections is paramount. Pre-exposure and post-exposure prophylaxis and antiviral suppressive therapeutic approaches are reviewed. Additionally, infection control practices specific to this patient population are discussed. A comprehensive approach utilizing each of these can be effective at reducing the negative impact of viral infections. PMID:22102619

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

    PubMed

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

    2015-05-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  11. The role of human papillomavirus in oral disease.

    PubMed

    Pringle, Gordon A

    2014-04-01

    A wide range of human papillomavirus (HPV) genotypes have been detected in oral mucosa. Clinical infections with low-risk genotypes manifest as squamous papilloma, condyloma acuminatum, verruca vulgaris, or multifocal epithelial hyperplasia. Clinical infections with high-risk genotypes have been associated with malignant lesions. The most common genotype isolated from subclinical infection is HPV-16. A causal role for HPV in carcinogenesis of oral squamous carcinoma is minimal. Ongoing vaccination against HPV types 6, 11, 16, and 18 is expected to decrease the spread of infection and decrease the carcinogenic potential of HPV-16 in the oropharynx and oral cavity. PMID:24655529

  12. [Malignant hyperthermia].

    PubMed

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

    2014-12-01

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

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

    PubMed Central

    Heimberger, Amy B.

    2011-01-01

    Background: High-grade primary and metastatic central nervous system (CNS) tumors are common, deadly, and refractory to conventional therapy and continue to be therapeutically challenging. A key nodal transcriptional factor, the signal transducer and activator of transcription 3 (STAT3), drives the fundamental components of tumor malignancy and metastases in the CNS by enhancing proliferation, angiogenesis, invasion, metastasis, and immunosuppression. The introduction of STAT3 inhibitors in clinical trials for this patient population is imminent. Methods: STAT3 inhibitors have been extensively tested in a variety of preclinical murine models. Results: The STAT3 inhibitor, WP1066, has displayed marked efficacy with minimal toxicity against malignancy in murine models, including established intracerebral tumors. The mechanism of this in vivo efficacy of the STAT3 blockade agents is a combination of direct tumor cytotoxicity and immune cytotoxic clearance. Conclusions: Given their direct antitumor cytotoxic effects, STAT3 inhibitors may exert therapeutic activity in the monotherapy setting but may also have compelling use as immunotherapeutic modulators or as a salvage therapy. PMID:22140648

  14. Malignant teratoma

    MedlinePLUS

    ... is often located in the front chest area (mediastinum). Most malignant teratomas can spread throughout the body, ... Diseases of the diaphragm, chest wall, pleura, and mediastinum. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

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

    PubMed

    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

    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

  16. The deregulated promoter methylation of the Polo-like kinases as a potential biomarker in hematological malignancies.

    PubMed

    Ward, Alejandra; Sivakumar, Gayathri; Kanjeekal, Sindu; Hamm, Caroline; Labute, Brayden C; Shum, David; Hudson, John W

    2015-07-01

    Deregulation of Polo-like kinase (PLK) transcription via promoter methylation results in perturbations at the protein level, which has been associated with oncogenesis. Our objective was to further characterize the methylation profile for PLK1-4 in bone marrow aspirates displaying blood neoplasms as well as in cells grown in vitro. Clinically, we have determined that more than 70% of lymphoma and myelodysplastic syndrome (MDS)/leukemia bone marrow extracts display a hypermethylated PLK4 promoter region in comparison to the normal. Decreased PLK4 protein expression due to promoter hypermethylation was negatively correlated with JAK2 overexpression, a common occurrence in hematological malignancies. In vitro examination of the PLKs under biologically relevant condition of 5% O2 revealed that the highly conserved PLKs respond to lower oxygen tension at both the DNA and the protein level. These findings suggest that PLK promoter methylation status correlates with disease and tumorigenesis in blood neoplasms and could serve as a biomarker. PMID:25347426

  17. Investigations on the potential of a low power diode pumped Er:YAG laser system for oral surgery

    NASA Astrophysics Data System (ADS)

    Stock, Karl; Wurm, Holger; Hausladen, Florian; Wagner, Sophia; Hibst, Raimund

    2015-02-01

    Flash lamp pumped Er:YAG-lasers are used in clinical practice for dental applications successfully. As an alternative, several diode pumped Er:YAG laser systems (Pantec Engineering AG) become available, with mean laser power of 2W, 15W, and 30W. The aim of the presented study is to investigate the potential of the 2W Er:YAG laser system for oral surgery. At first an appropriate experimental set-up was realized with a beam delivery and both, a focusing unit for non-contact tissue cutting and a fiber tip for tissue cutting in contact mode. In order to produce reproducible cuts, the samples (porcine gingiva) were moved by a computer controlled translation stage. On the fresh samples cutting depth and quality were determined by light microscopy. Afterwards histological sections were prepared and microscopically analyzed regarding cutting depth and thermal damage zone. The experiments show that low laser power ? 2W is sufficient to perform efficient oral soft tissue cutting with cut depth up to 2mm (sample movement 2mm/s). The width of the thermal damage zone can be controlled by the irradiation parameters within a range of about 50?m to 110?m. In general, thermal injury is more pronounced using fiber tips in contact mode compared to the focused laser beam. In conclusion the results reveal that even the low power diode pumped Er:YAG laser is an appropriate tool for oral surgery.

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

    PubMed Central

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

    2013-01-01

    A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and “macaque versions” of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides. PMID:24312248

  19. Poly-α,β-Polyasparthydrazide-Based Nanogels for Potential Oral Delivery of Paclitaxel: In Vitro and In Vivo Properties.

    PubMed

    Guo, Jingwen; Ma, Mingxin; Chang, Di; Zhang, Qiang; Zhang, Chen; Yue, Yang; Liu, Jia; Wang, Siling; Jiang, Tongying

    2015-12-01

    A family of nanogel drug carriers has been designed to enhance the oral absorption of paclitaxel (PTX). The PAHy-based nanogels were prepared by the interpenetration of poly-α,β-polyasparthydrazide (PAHy) chains and dicarboxyl-poly (ethylene glycol) (CPEG), forming a smart chain network. The PAHy-based nanogels were characterized by Fourier Transform Infrared Spectroscopy (FT-IR), dynamic light scattering (DLS), X-ray diffraction (XRD) and high performance liquid chromatography (HPLC). The adhesion and retention properties of fluorescein isothiocyanate (FITC)-nanogels in vivo were investigated using an in vivo imaging system and confocal laser scanning microscopy (CLSM). The smart nanogels had a particle size of -200 nm, increased the degree and rate of release, and spent over 12 h in the gastrointestinal tract. They also produced excellent adhesion, permeability and retention (APR) effects and increased oral absorption, confirming their use as potential sustained-release carriers for the oral delivery of the hydrophobic anticancer agent PTX. PMID:26510316

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

    PubMed Central

    Palombo, Enzo A.

    2011-01-01

    Oral diseases are major health problems with dental caries and periodontal diseases among the most important preventable global infectious diseases. Oral health influences the general quality of life and poor oral health is linked to chronic conditions and systemic diseases. The association between oral diseases and the oral microbiota is well established. Of the more than 750 species of bacteria that inhabit the oral cavity, a number are implicated in oral diseases. The development of dental caries involves acidogenic and aciduric Gram-positive bacteria (mutans streptococci, lactobacilli and actinomycetes). Periodontal diseases have been linked to anaerobic Gram-negative bacteria (Porphyromonas gingivalis, Actinobacillus, Prevotella and Fusobacterium). Given the incidence of oral disease, increased resistance by bacteria to antibiotics, adverse affects of some antibacterial agents currently used in dentistry and financial considerations in developing countries, there is a need for alternative prevention and treatment options that are safe, effective and economical. While several agents are commercially available, these chemicals can alter oral microbiota and have undesirable side-effects such as vomiting, diarrhea and tooth staining. Hence, the search for alternative products continues and natural phytochemicals isolated from plants used as traditional medicines are considered as good alternatives. In this review, plant extracts or phytochemicals that inhibit the growth of oral pathogens, reduce the development of biofilms and dental plaque, influence the adhesion of bacteria to surfaces and reduce the symptoms of oral diseases will be discussed further. Clinical studies that have investigated the safety and efficacy of such plant-derived medicines will also be described. PMID:19596745

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

    PubMed Central

    Knippels, Léon M J; Penninks, André H

    2003-01-01

    The need for widely accepted and validated animal models to test the potential allergenicity and potency of novel (biotechnology-derived) proteins has become an important issue for their safety evaluation. In this article, we summarize the results of the development of an oral sensitization protocol for food proteins in the rat. Young Brown Norway rats were exposed to either various purified allergenic proteins (e.g., ovalbumin, partly purified), a whole food (cow's milk), or total protein extracts (hen's egg white, peanut) by daily gavage dosing during 42 days without the use of an adjuvant. The results showed that Brown Norway rats can be sensitized orally to the various allergenic food proteins tested, resulting in antigen-specific immunoglobulin (Ig) G and IgE responses, without the use of adjuvants. Animals orally exposed to cow's milk or total protein extracts of egg white also developed specific IgE and IgG antibodies that recognized the same proteins compared with antibodies from patients allergic to egg white or cow's milk. We also studied local and systemic immune-mediated effects. In ovalbumin-sensitized rats, some clinical symptoms of food allergy were studied upon an oral challenge with ovalbumin. The results demonstrated that gut permeability was increased and that in some animals breathing frequency and systolic blood pressure were temporarily decreased. The results obtained show that the Brown Norway rat provides a suitable animal model for food allergy research and for the study of relative allergenicity of existing and novel food proteins. PMID:12573912

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

    TOXLINE Toxicology Bibliographic Information

    Lou K; Yao Y; Hoye AT; James MJ; Cornec AS; Hyde E; Gay B; Lee VM; Trojanowski JQ; Smith AB 3rd; Brunden KR; Ballatore C

    2014-07-24

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

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

    PubMed

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

    2014-07-24

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

  4. The potential of CD44 as a diagnostic and prognostic tool in oral cancer.

    PubMed

    Emich, Helena; Chapireau, David; Hutchison, Iain; Mackenzie, Ian

    2015-07-01

    The CD44 family of molecules exists as a wide range of isoforms ubiquitously expressed on the surface of mammalian cells. The variation in patterns of CD44 expression on cancer cells has been widely studied in relation to their behaviour, and further interest has recently arisen in CD44 as a marker of the subfraction tumour cells acting as cancer stem cells in several types of tumours. This review focuses on the patterns of CD44 expression on the stem cell fraction of oral squamous cell carcinoma and on the relationship of detectably different patterns of CD44 expression to the behaviour of tumours. PMID:25640063

  5. Oral manifestations of hepatitis C virus infection

    PubMed Central

    Carrozzo, Marco; Scally, Kara

    2014-01-01

    Extrahepatic manifestations (EHMs) of hepatitis C virus (HCV) infection can affect a variety of organ systems with significant morbidity and mortality. Some of the most frequently reported EHM of HCV infection, involve the oral region predominantly or exclusively. Oral lichen planus (OLP) is a chronic inflammatory condition that is potentially malignant and represents cell-mediated reaction to a variety of extrinsic antigens, altered self-antigens, or super antigens. Robust epidemiological evidence support the link between OLP and HCV. As the virus may replicate in the oral mucosa and attract HCV-specific T lymphocytes, HCV may be implicated in OLP pathogenesis. Sjögren syndrome (SjS) is an autoimmune exocrinopathy, characterized by dryness of the mouth and eyes and a multitude of other systemic signs and symptoms. SjS patients have also an increased risk of non-Hodgkin lymphoma. Patients with chronic hepatitis C do frequently have histological signs of Sjögren-like sialadenitis with mild or even absent clinical symptoms. However, it is still unclear if HCV may cause a disease mimicking SjS or it is directly responsible for the development of SjS in a specific subset of patients. Oral squamous cell carcinoma is the most common oral malignant tumour and at least in some part of the world could be linked to HCV. PMID:24976694

  6. No significant association between malignancy and topical use of pimecrolimus

    PubMed Central

    Margolis, David J; Abuabara, Katrina; Hoffstad, Ole; Wan, Joy; Raimondo, Denise; Bilker, Warren

    2015-01-01

    Importance A black box warning describes a potential risk of malignancy associated with the topical use of pimecrolimus to treat atopic dermatitis (AD) due to its similarity to oral calcineurin inhibitors used in solid organ transplantation and spontaneous reporting of malignancies including lymphomas and cutaneous malignancies. Objective The goal of this study was to evaluate the risk of malignancy in a post marketing study of children exposed to pimecrolimus. Design A longitudinal cohort study. Setting A nation-wide ongoing long-term cohort of children with AD. Participants Children enrolled in the Pediatric Eczema Elective Registry (PEER) who had a history of AD and pimecrolimus use. Main outcome Reports of malignancy in those in PEER as compared to expected rates from the Surveillance Research (SEER) Program. Results 7,457 subjects were enrolled in the PEER study for a total of 26,792 person-years. Children used a mean of 793 (SD 1356) grams of pimecrolimus while enrolled in the study. As of May 2014, 5 malignancies had been reported. These include 2 leukemias, 1 osteosarcoma, and 2 lymphomas. No skin cancers were reported. The Standardized Incidence Ratio (SIR) for all malignancies (primary outcome) based on the age standardized SEER population was 1.2 (0.5, 2.8). As secondary analyses, the SIR (based on 2 cases for each) for lymphoma was 2.9 (0.7, 11.7) and for leukemia was 2.0 (0.5, 8.2). None of these findings were statistically significant. Conclusions and Relevance Based on more than 25,000 person-years of follow-up it seems unlikely that topical pimecrolimus as it was used in the PEER cohort to treat AD is associated with an increased risk of malignancy. PMID:25692459

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

    PubMed Central

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

    2008-01-01

    Background Metastatic melanoma is a severe disease. Few experimental animal models of metastatic melanoma exist. MeLiM minipigs exhibit spontaneous melanoma. Cutaneous and metastatic lesions are histologically similar to human's. However, most of them eventually spontaneously regress. Our purpose was to investigate whether the MeLiM model could reveal markers of malignancy in human melanocytic proliferations. Results We compared the serial analysis of gene expression (SAGE) between normal pig skin melanocytes and melanoma cells from an early pulmonary metastasis of MeLiM minipigs. Tag identification revealed 55 regulated genes, including GNB2L1 which was found upregulated in the melanoma library. In situ hybridisation confirmed GNB2L1 overexpression in MeLiM melanocytic lesions. GNB2L1 encodes the adaptor protein RACK1, recently shown to influence melanoma cell lines tumorigenicity. We studied the expression of RACK1 by immunofluorescence and confocal microscopy in tissues specimens of normal skin, in cutaneous and metastatic melanoma developped in MeLiM minipigs and in human patients. In pig and human samples, the results were similar. RACK1 protein was not detected in normal epidermal melanocytes. By contrast, RACK1 signal was highly increased in the cytoplasm of all melanocytic cells of superficial spreading melanoma, recurrent dermal lesions and metastatic melanoma. RACK1 partially colocalised with activated PKC??. In pig metastases, additional nuclear RACK1 did not associate to BDNF expression. In human nevi, the RACK1 signal was low. Conclusion RACK1 overexpression detected in situ in human melanoma specimens characterized cutaneous and metastatic melanoma raising the possibility that RACK1 can be a potential marker of malignancy in human melanoma. The MeLiM strain provides a relevant model for exploring mechanisms of melanocytic malignant transformation in humans. This study may contribute to a better understanding of melanoma pathophysiology and to progress in diagnosis. PMID:18442364

  8. Malignant Tourette syndrome.

    PubMed

    Cheung, Min-Yuen Cynthia; Shahed, Joohi; Jankovic, Joseph

    2007-09-15

    The aim of this work was to draw attention to potentially life-threatening symptoms associated with Tourette syndrome (TS) and to explore their relationship to TS comorbidities. Medical records of all patients with TS evaluated at our Movement Disorders Clinic between July 2003 and July 2006 were reviewed. Data on patients with malignant TS, defined as >or=2 emergency room (ER) visits or >or=1 hospitalizations for TS symptoms or its associated behavioral comorbidities, were entered into a dataset and analyzed. Five illustrative cases are described. Of 333 TS patients evaluated during the 3-year period, 17 (5.1%) met the criteria for malignant TS. Hospital admission or ER visits were for tic-related injuries, self-injurious behavior (SIB), uncontrollable violence and temper, and suicidal ideation/attempts. Compared with patients with nonmalignant TS, those with malignant TS were significantly more likely to have a personal history of obsessive compulsive behavior/disorder (OCB/OCD), complex phonic tics, coprolalia, copropraxia, SIB, mood disorder, suicidal ideation, and poor response to medications. Although TS is rarely a disabling disorder, about 5% of patients referred to a specialty clinic have life-threatening symptoms. Malignant TS is associated with greater severity of motor symptoms and the presence of >or=2 behavioral comorbidities. OCD/OCB in particular may play a central role in malignant TS; obsessive compulsive qualities were associated with life-threatening tics, SIB, and suicidal ideation. Malignant TS is more refractory to medical treatment than nonmalignant TS. PMID:17566119

  9. Can MMP-9 be a Prognosticator Marker for Oral Squamous Cell Carcinoma?

    PubMed Central

    Basu, Shiva Kumar; Kumar, Manish

    2016-01-01

    Introduction Invasion and metastasis of malignant tumours severely endanger the life of cancer patients. Squamous cell carcinoma is one of the commonly found malignancies in the oral cavity and its survival rate has not improved from past few decades. Since an important risk factor for oral squamous cell carcinoma is the presence of epithelial dysplasia, it is necessary to check the presence of a prognosticator marker in both of them. As matrix metalloproteinase’s (MMP’s) are involved in degradation of type IV collagen, which are one of the important components of extracellular matrix components which play a relevant role in several steps of tumour progression such as invasion and metastasis. We have studied MMP-9 expression to evaluate its prognostic potential in oral cancers as well as oral epithelial dysplasia along with tissues of normal oral epithelium. Materials and Methods The expression was examined using immunohistochemistry procedure with MMP-9 in 100 samples including cases of epithelium from normal oral mucosa, oral dysplastic lesions and oral squamous cell carcinoma. One set of formalin fixed, paraffin embedded sections of the three categories were stained by haematoxylin and eosin. The sections were then evaluated under microscope. Data was examined for statistical significance using SPSS 13.0 by Mann-Whitney Test and Kruskal-Wallis Test. Results With MMP-9 gain of expression was noted from Control group to oral squamous cell carcinoma. Cytoplasmic staining was seen with MMP-9. Statistically highly significant differences were seen between oral epithelial dysplasia and oral squamous cell carcinoma and statistically significant differences were found between the control group and the oral squamous cell carcinoma group. Conclusion This study suggested that oral squamous cell carcinoma shows higher MMP-9 expression as compared to oral epithelial dysplasia followed by epithelium from normal oral mucosa. However, no correlation was found among the histological grades of oral squamous cell carcinoma. PMID:26894167

  10. Contaminated tooth brushes–potential threat to oral and general health

    PubMed Central

    Naik, Rashmi; Ahmed Mujib, B. R.; Telagi, Neethu; Anil, B. S.; Spoorthi, B. R.

    2015-01-01

    Background: Tooth brushing is most common method of maintaining oral hygiene. In removing plaque and other soft debris from the teeth, tooth brushes become contaminated with bacteria, blood, saliva and oral debris. These contaminated tooth brushes can be a source of infection. Aims and objectives: The aim of the present study was to evaluate the presence of microorganisms in the tooth brushes and to investigate the effect of disinfectants such as chlorhexidine gluconate, sodium hypochlorite and water to decontaminate them. Materials and Methods: Twenty-one children were asked to brush their teeth for 5 days with a tooth brush. The tooth brushes were put in Robertson's Cooked Meat broth and were observed for growth of Streptococcal microorganisms. These tooth brushes were then placed in disinfectants such as 0.2% chlorhexidine gluconate (Group I), 1% sodium hypochlorite (Group II) and water (Group III) for 24 hrs and then cultured again. Reduction of growth of microorganisms was seen in Group I, Group II and remnants of growth seen in Group III. Conclusion: We conclude that the use of disinfectant for a tooth brush is a must for every individual at least at regular intervals. PMID:26288790

  11. Do oral bacteria alter the regenerative potential of stem cells? A concise review

    PubMed Central

    Chatzivasileiou, Kyriaki; Kriebel, Katja; Steinhoff, Gustav; Kreikemeyer, Bernd; Lang, Hermann

    2015-01-01

    Mesenchymal stem cells (MSCs) are widely recognized as critical players in tissue regeneration. New insights into stem cell biology provide evidence that MSCs may also contribute to host defence and inflammation. In case of tissue injury or inflammatory diseases, e.g. periodontitis, stem cells are mobilized towards the site of damage, thus coming in close proximity to bacteria and bacterial components. Specifically, in the oral cavity, complex ecosystems of commensal bacteria live in a mutually beneficial state with the host. However, the formation of polymicrobial biofilm communities with pathogenic properties may trigger an inadequate host inflammatory-immune response, leading to the disruption of tissue homoeostasis and development of disease. Because of their unique characteristics, MSCs are suggested as crucial regulators of tissue regeneration even under such harsh environmental conditions. The heterogeneous effects of bacteria on MSCs across studies imply the complexity underlying the interactions between stem cells and bacteria. Hence, a better understanding of stem cell behaviour at sites of inflammation appears to be a key strategy in developing new approaches for in situ tissue regeneration. Here, we review the literature on the effects of oral bacteria on cell proliferation, differentiation capacity and immunomodulation of dental-derived MSCs. PMID:26058313

  12. Attenuated Salmonella typhimurium SV4089 as a Potential Carrier of Oral DNA Vaccine in Chickens

    PubMed Central

    Jazayeri, Seyed Davoud; Ideris, Aini; Zakaria, Zunita; Omar, Abdul Rahman

    2012-01-01

    Attenuated Salmonella has been used as a carrier for DNA vaccine. However, in vitro and in vivo studies on the bacteria following transfection of plasmid DNA were poorly studied. In this paper, eukaryotic expression plasmids encoding avian influenza virus (AIV) subtype H5N1 genes, pcDNA3.1/HA, NA, and NP, were transfected into an attenuated Salmonella enteric typhimurium SV4089. In vitro stability of the transfected plasmids into Salmonella were over 90% after 100 generations. The attenuated Salmonella were able to invade MCF-7 (1.2%) and MCF-10A (0.5%) human breast cancer cells. Newly hatched specific-pathogen-free (SPF) chicks were inoculated once by oral gavage with 109 colony-forming unit (CFU) of the attenuated Salmonella. No abnormal clinical signs or deaths were recorded after inoculation. Viable bacteria were detected 3 days after inoculation by plating from spleen, liver, and cecum. Fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR) were carried out for confirmation. Salmonella was not detected in blood cultures although serum antibody immune responses to Salmonella O antiserum group D1 factor 1, 9, and 12 antigens were observed in all the inoculated chickens after 7 days up to 35 days. Our results showed that live attenuated S. typhimurium SV4089 harboring pcDNA3.1/HA, NA, and NP may provide a unique alternative as a carrier for DNA oral vaccine in chickens. PMID:22701301

  13. An overview of epidemiology and common risk factors for oral squamous cell carcinoma.

    PubMed

    McDowell, John D

    2006-04-01

    Understanding the epidemiologic picture and the risk factors for oral cancer can help identify and treat patients at risk for oral cancers. Early diagnosis of an oral cancer continues to be important to achieving a favorable prognosis. Absent a diagnosis of oral/pharyngeal cancer, there clearly can-lot be an effective treatment plan. Discovering a potentially malignant or malignant lesion and through biopsy reaching a diagnosis for the lesion begins by performing an examination with the purpose of detecting oral/pharyngeal lesions. An oral cancer screening can be performed in less than five minutes without any expensive diagnostic aids. Despite the ease with which this exam can be performed and the noninvasive nature of the examination,most patients report that they have never had an oral cancer examination. Late stage diagnosis continues to be a common situation resulting in high rates of morbidity and mortality. Without early recognition it seems that the trend of late stage diagnosis will continue. Physicians, dentists, and other health care providers should be performing the oral cancer screening examination on a routine basis for all of their patients.Note: For the interested clinician, the author highly recommends an excellent comprehensive text on the subject of oral cancer. Sol Silverman's(with multiple contributors) The American Cancer Society's Atlas of Clinical Oncology Oral Cancer: Fifth Edition by BC Decker Publishers is an excellent overview of oral cancer covering in greater detail many of the subjects that could not be covered in this brief article. Additionally, there are excellent color photographs of the common presentations of oral malignancies that can be helpful in assessing oral/pharyngeal lesions. PMID:16580911

  14. Epithelial Dysplasia in Oral Cavity

    PubMed Central

    Shirani, Samaneh; Kargahi, Neda; Razavi, Sayed Mohammad; Homayoni, Solmaz

    2014-01-01

    Among oral lesions, we encounter a series of malignant epithelial lesions that go through clinical and histopathologic processes in order to be diagnosed. Identifying these processes along with the etiology knowledge of these lesions is very important in prevention and early treatments. Dysplasia is the step preceding the formation of squamous cell carcinoma in lesions which have the potential to undergo dysplasia. Identification of etiological factors, clinical and histopathologic methods has been the topic of many articles. This article, reviews various articles presenting oral cavity dysplasia, new clinical methods of identifying lesions, and the immunohistochemical research which proposes various markers for providing more precise identification of such lesions. This article also briefly analyzes new treatment methods such as tissue engineering. PMID:25242838

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

    PubMed Central

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

    2013-01-01

    Cancer of the oral cavity is a serious disease, affecting about 30,000 individuals in US annually. There are several animal models of oral cancer, but each has certain disadvantages. As a new model, we investigated whether topical application of the tobacco smoke carcinogen, dibenzo[a,l]pyrene (DB[a,l]P) is mutagenic and carcinogenic in the oral cavity of the B6C3F1 lacI and B6C3F1 mouse, respectively. B6C3F1 lacI mice received DB[a,l]P (0, 3, 6, 12 nmol) 3× per week. B6C3F1 mice received the same doses and also 24 nmol. At 38 weeks mutagenesis was measured in oral tissues in lacI mice. For the high dose group, the mutant fraction (MF) in upper mucosa and tongue increased about twofold relative to that in vehicle-alone. The increases were statistically significant. The mutational profile in the DB[a,l]P-induced mutants was compared with that induced by benzo[a]pyrene (BaP) in oral tissue. BaP is mutagenic in many tissues when administered by gavage. The mutational profile for DB[a,l]P was more similar to that reported for p53 mutations in head and neck cancers than was that of BaP. At 47 weeks, oral squamous cell carcinomas (OSCC) were found in 31% of the high-dose B6C3F1 group. Elevations of p53 and COX-2 protein were observed in tumor and dysplastic tissue. As DB[a,l]P induces mutations and tumors in the oral cavity, and has a mutational profile in oral tissue similar to that found in p53 in human OSCC, the treatment protocol described here may represent a new and relevant model for cancer of the oral cavity. PMID:21815141

  16. Malignant mesothelioma.

    PubMed

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

    2008-01-01

    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

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

    PubMed Central

    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

    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

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

    PubMed Central

    Liu, Qun; Zheng, Chanjiao; Shen, Huanyu; Zhou, Zhiheng; Lei, Yixiong

    2015-01-01

    Background. Our study was designed to elucidate whether there were miRNA and mRNA aberrantly expression profiles and potential role in malignant transformation of 16HBE induced by Cd. Methods. mRNA and miRNA expression profiles were determined in 35th Cd-induced 16HBE and untreated 16HBE by microarray. A series of bioinformatics analyses such as predicting targets, GO, KEGG were performed to find DEGs, coexpressing networks between miRNAs and mRNAs and its functions. Results. 498 DEGs were found. 8 Cd-responsive novel miRNAs predicted previously were identified, and 5 of them were downregulated. 214 target genes were predicted for the Cd-responsive miRNAs, many of which appeared to regulate gene networks. Target gene CCM2 was showed reciprocal effect by miRNAs. According to the combination analysis, hsa-miR-27b-3p regulated most of the mRNAs, especially upregulated expression genes. The differentially expressed miRNAs are involved in the biological processes and channels, and these GO and KEGG enrichment analyses result were significantly enriched in the Cd-responsive. Discussion. These results provided a tight link for the miRNA-mRNA integrated network and implied the role of novel miRNAs in malignant transformation of 16HBE induced by Cadmium. It is better to understand the novel molecular mechanism of cadmium-induced tumorigenesis. PMID:26504844

  19. Pathogenesis and therapeutic intervention of oral submucous fibrosis

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2008-07-01

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

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

    PubMed

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

    2008-03-15

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

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

    PubMed Central

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

    2013-01-01

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

  3. Simulants of Malignant Melanoma

    PubMed Central

    Piérard-Franchimont, Claudine; Delvenne, Philippe

    2015-01-01

    During the recent period, dermoscopy has yielded improvement in the early disclosure of various atypical melanocytic neoplasms (AMN) of the skin. Beyond this clinical procedure, AMN histopathology remains mandatory for establishing their precise diagnosis. Of note, panels of experts in AMN merely report moderate agreement in various puzzling cases. Divergences in opinion and misdiagnosis are likely increased when histopathological criteria are not fine-tuned and when facing a diversity of AMN types. Furthermore, some AMN have been differently named in the literature including atypical Spitz tumor, metastasizing Spitz tumor, borderline and intermediate melanocytic tumor, malignant Spitz nevus, pigmented epithelioid melanocytoma or animal-type melanoma. Some acronyms have been further suggested such as MELTUMP (after melanocytic tumor of uncertain malignant potential) and STUMP (after Spitzoid melanocytic tumor of uncertain malignant potential). In this review, such AMN at the exclusion of cutaneous malignant melanoma (MM) variants, are grouped under the tentative broad heading skin melanocytoma. Such set of AMN frequently follows an indolent course, although they exhibit atypical and sometimes worrisome patterns or cytological atypia. Rare cases of skin melanocytomas progress to loco regional clusters of lesions (agminate melanocytomas), and even to regional lymph nodes. At times, the distinction between a skin melanocytoma and MM remains puzzling. However, multipronged immunohistochemistry and emerging molecular biology help profiling any malignancy risk if present. PMID:26779311

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

    PubMed Central

    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

    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

  5. Hematologic malignancies

    SciTech Connect

    Hoogstraten, B.

    1986-01-01

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

  6. Potential of erlotinib cyclodextrin nanosponge complex to enhance solubility, dissolution rate, in vitro cytotoxicity and oral bioavailability.

    PubMed

    Dora, Chander Parkash; Trotta, Francesco; Kushwah, Varun; Devasari, Naresh; Singh, Charan; Suresh, Sarasija; Jain, Sanyog

    2016-02-10

    The present study was envisaged to evaluate the effect of erlotinib ?-cyclodextrin nanosponge (ERL-NS) on the solubility, dissolution, in vitro cytotoxicity and oral bioavailability of erlotinib (ERL). Preliminary studies were conducted to select the optimized stoichiometry concentration of ERL and NS. The drug nanosponge complex comprising of 1:4 proportions of ERL and NS was prepared by freeze drying. ERL-NS formed nanoparticles of 372±31nm size with narrow size distribution (0.21±0.07 PDI) and high zeta potential (-32.07±4.58mV). The complexation phenomenon was confirmed by DSC, SEM, PXRD, FTIR, and TEM studies. In vitro dissolution studies revealed an increased dissolution rate (2-folds) with an enhanced dissolution efficiency of the nanosponge complex in comparison to pure drug. In vitro cytotoxicity study and apoptosis assay in pancreatic cell lines (MIA PaCa-2 and PANC-1) indicates the increased toxicity of ERL-NS. Both, quantitative and qualitative cell uptake studies unveiled the higher uptake efficiency of ERL-NS than free drug. ERL-NS showed enhanced oral bioavailability with 1.8-fold higher Cmax (78.98±6.2 vs. 42.36±1.75?g/ml), and ?2-fold AUC0-? (1079.95±41.38 vs. 580.43±71.91), in comparison to pure ERL. Therefore, we conclude that the formation of a complex of nanosponge with ERL is a successful approach to increase its solubility, dissolution and oral bioavailability which may ultimately result in reduction in dose and dose related side-effects. PMID:26686138

  7. Oral soft tissue biopsies in Oporto, Portugal: An eight year retrospective analysis

    PubMed Central

    Guedes, Manuel-Moreira; Albuquerque, Rui; Monteiro, Marta; Lopes, Carlos-Alberto; do Amaral, José-Barbas; Pacheco, José-Júlio

    2015-01-01

    Background The diseases that affect the oral cavity are wide and diverse, comprising a broad spectrum of either benign or malignant lesions. However, few histological-based studies were performed for the evaluation of oral cavity lesions, and very few directed to oral soft tissue pathology. The aim of this study was to carry out pioneering research, within a Portuguese population, to determine the frequency and characteristics of oral malignancies, potential malignant disorders, and soft benign tissues pathologies submitted for biopsy in a north Portugal (Oporto) hospital population. Material and Methods We performed a retrospective study of soft tissue, oral cavity biopsies, in a hospital north of Portugal (Oporto) between 1999 and 2006. We analysed information on gender, age, location of the lesion, and the histopathological diagnosis. Results A total of 1042 oral biopsies were observed, 557(53.5%) in females and 485 (46.5%) in males, with a mean age of 51.7 years (S.D. ±17.6). The topographic location most frequently affected was labial mucosa (n=306). Considering the nature of the lesions, 700 (67.2%) corresponded to non-neoplasic lesions, 45 (4.3%) to potentially malignant disorders, and 297 (28.5%) to neoplasms (93 benign and 204 malignant). Non-neoplasic lesions were more prevalent in female gender (59.9%) when compared with potentially malignant disorders (46.7%) and neoplasms (39.4%) (P< 0.001). Non-neoplasic lesions presented the lower mean age (49.2±17.6) and potentially malignant disorders the highest mean age (60.5±14.5) (P< 0.001). The most common lesion of entire sample was fibro-epithelial hyperplasia (n=186; 17.9%), followed by squamous cell carcinoma (n=158; 15.1%). Conclusions Fibro-epithelial hyperplasia, followed by squamous cell carcinoma, was the most common pathologies. This pioneering study provided, for the first time, data about the proportion of squamous cell carcinoma when compared with benign conditions in a Portuguese hospital population. Key words:Oral biopsies, oral cavity, oral pathology, Portugal, soft tissue lesions. PMID:26644842

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

    PubMed

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

    2014-07-01

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

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

    PubMed

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

    2011-06-01

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

  10. Live oral Salmonella vaccines: potential use of attenuated strains as carriers of heterologous antigens to the immune system.

    PubMed

    Dougan, G; Hormaeche, C E; Maskell, D J

    1987-03-01

    Live attenuated strains of salmonellae are showing promise as live oral vaccines against human typhoid fever and other Salmonella infections of man and animals. Attenuation can be achieved by introducing genetically defined, non-reverting mutations into specific genes on the Salmonella chromosome. Mutations in the gal E or aroA genes of Salmonella inhibit the ability of the bacteria to grow in vivo, and strains carrying such lesions are effective vaccines against salmonellosis. Genetic determinants encoding for the expression of potentially protective antigens from heterologous, non-Salmonella pathogens can be readily introduced into these attenuated Salmonella strains. Expression of the heterologous antigen does not affect the ability of the Salmonella host to be used as a Salmonella vaccine. Mice infected orally with a Salmonella typhimurium aroA vaccine expressing the Escherichia coli heat-labile toxin B subunit developed both a secretory and serum antibody response to this antigen. These serum antibodies were able to neutralise the activity of E. coli heat-labile toxin in tissue culture assays. A humoral and cell-mediated (DTH) immune response was detected against beta galactosidase, an intracellular antigen, in mice infected with an aroA vaccine expressing this cloned antigen. The prospects for the development of live Salmonella vaccines as a method for delivering heterologous antigens derived from bacteria, viruses and parasites is discussed. PMID:3106921

  11. Mathematical Models to Explore Potential Effects of Supersaturation and Precipitation on Oral Bioavailability of Poorly Soluble Drugs.

    PubMed

    Kleppe, Mary S; Forney-Stevens, Kelly M; Haskell, Roy J; Bogner, Robin H

    2015-07-01

    Poorly soluble drugs are increasingly formulated into supersaturating drug delivery systems which may precipitate during oral delivery. The link between in vitro drug concentration profiles and oral bioavailability is under intense investigation. The objective of the present work was to develop closed-form analytical solutions that relate in vitro concentration profiles to the amount of drug absorbed using several alternate assumptions and only six parameters. Three parameters define the key features of the in vitro drug concentration-time profile. An additional three parameters focus on physiological parameters. Absorption models were developed based on alternate assumptions; the drug concentration in the intestinal fluid: (1) peaks at the same time and concentration as in vitro, (2) peaks at the same time as in vitro, or (3) reaches the same peak concentration as in vitro. The three assumptions provide very different calculated values of bioavailability. Using Case 2 assumptions, bioavailability enhancement was found to be less than proportional to in silico examples of dissolution enhancement. Case 3 assumptions lead to bioavailability enhancements that are more than proportional to dissolution enhancements. Using Case 1 predicts drug absorption amounts that fall in between Case 2 and 3. The equations developed based on the alternate assumptions can be used to quickly evaluate the potential improvement in bioavailability due to intentional alteration of the in vitro drug concentration vs. time curve by reformulation. These equations may be useful in making decisions as to whether reformulation is expected to provide sufficient bioavailability enhancement to justify the effort. PMID:25851513

  12. Localization and osteoblastic differentiation potential of neural crest-derived cells in oral tissues of adult mice.

    PubMed

    Ono, Miki; Suzawa, Tetsuo; Takami, Masamichi; Yamamoto, Gou; Hosono, Tomohiko; Yamada, Atsushi; Suzuki, Dai; Yoshimura, Kentaro; Watahiki, Junichi; Hayashi, Ryuhei; Arata, Satoru; Mishima, Kenji; Nishida, Kohji; Osumi, Noriko; Maki, Koutaro; Kamijo, Ryutaro

    2015-09-01

    In embryos, neural crest cells emerge from the dorsal region of the fusing neural tube and migrate throughout tissues to differentiate into various types of cells including osteoblasts. In adults, subsets of neural crest-derived cells (NCDCs) reside as stem cells and are considered to be useful cell sources for regenerative medicine strategies. Numerous studies have suggested that stem cells with a neural crest origin persist into adulthood, especially those within the mammalian craniofacial compartment. However, their distribution as well as capacity to differentiate into osteoblasts in adults is not fully understood. To analyze the precise distribution and characteristics of NCDCs in adult oral tissues, we utilized an established line of double transgenic (P0-Cre/CAG-CAT-EGFP) mice in which NCDCs express green fluorescent protein (GFP) throughout their life. GFP-positive cells were scattered like islands throughout tissues of the palate, gingiva, tongue, and buccal mucosa in adult mice, with those isolated from the latter shown to form spheres, typical cell clusters composed of stem cells, under low-adherent conditions. Furthermore, GFP-positive cells had markedly increased alkaline phosphatase (a marker enzyme of osteoblast differentiation) activity and mineralization as shown by alizarin red staining, in the presence of bone morphogenetic protein (BMP)-2. These results suggest that NCDCs reside in various adult oral tissues and possess potential to differentiate into osteoblastic cells. NCDCs in adults may be a useful cell source for bone regeneration strategies. PMID:26225748

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

    PubMed Central

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

    2013-01-01

    Various herb products derived from plants have potent biological effects including anticancer activity. In the present study, the antitumor activity of a herbal product derived from the Scutellaria baicalensis (S. baicalensis) was examined, using in vitro assays in a human oral squamous cell carcinoma (OSCC) cell line. Results showed that S. baicalensis root extract at the concentration of 100 ?g/ml inhibited monolayer- and anchorage-independent growth in human OSCC cell lines, while not affecting the adhering abilities of cells. This suggested that it did not alter the expression of any of the adhesion receptors that mediate cell-extracellular matrix (ECM) interactions. The S. baicalensis root extract demonstrated potent cytostatic and apoptotic effects due to the downregulation of the cyclin-dependent kinase 4 expression and its partner cyclin D1, resulting in G1 arrest and poly (ADP-ribose) polymerase (PARP) cleavage. Additionally, the S. baicalensis root extract was found to have blocked vascular endothelial growth factor (VEGF)-induced migration and tube formation in human endothelial cells. Taken together, these results demonstrate that as a herbal product, the S. baicalensis root extract is a potential inhibitor of tumori- and angiogenesis and may be valuable in the development of pharmaceutical medications for the treatment of oral squamous cell carcinoma. PMID:24649131

  14. A potential oral anticancer drug candidate, Moringa oleifera leaf extract, induces the apoptosis of human hepatocellular carcinoma cells

    PubMed Central

    JUNG, IL LAE; LEE, JU HYE; KANG, SE CHAN

    2015-01-01

    It has previously been reported that cold water-extracts of Moringa oleifera leaf have anticancer activity against various human cancer cell lines, including non-small cell lung cancer. In the present study, the anticancer activity of M. oleifera leaf extracts was investigated in human hepatocellular carcinoma HepG2 cells. By the analysis of apoptotic signals, including the induction of caspase or poly(ADP-ribose) polymerase cleavage, and the Annexin V and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays, it was demonstrated that M. oleifera leaf extracts induce the apoptosis of HepG2 cells. In the hollow fiber assay, oral administration of the leaf extracts significantly reduced (44–52%) the proliferation of the HepG2 cells and A549 non-small cell lung cancer cells. These results support the potential of soluble extracts of M. oleifera leaf as orally administered therapeutics for the treatment of human liver and lung cancers. PMID:26622717

  15. Salivaomics for oral diseases biomarkers detection.

    PubMed

    Tasoulas, Jason; Patsouris, Efstratios; Giaginis, Constantinos; Theocharis, Stamatios

    2016-03-01

    The variation of saliva composition in different physiological and pathological states is well demonstrated. Several saliva constituents (enzymes, hormones, antibodies, cytokines etc.) are up- or down-regulated in respect to benign, premalignant and malignant conditions in the oral cavity, and several patterns of deregulation are associated with specific disorders. Omics technologies have contributed significantly in the identification of alterations in gene expression, transcription, protein coding and small molecules concentration, in biologic systems. In this aspect, salivaomics integrate these technologies in saliva analysis and represent a novel and holistic approach in oral disease management including diagnosis, prognosis and monitoring. This review summarizes the current research in the discovery of biomarkers and molecular signatures with diagnostic or prognostic utility for oral diseases in saliva. The review also focuses on the emerging issues of the salivaomics technology and saliva diagnostics and the translational potential. PMID:26680995

  16. Oral pigmentation: A review

    PubMed Central

    Sreeja, C.; Ramakrishnan, K.; Vijayalakshmi, D.; Devi, M.; Aesha, I.; Vijayabanu, B.

    2015-01-01

    Pigmentations are commonly found in the mouth. They represent in various clinical patterns that can range from just physiologic changes to oral manifestations of systemic diseases and malignancies. Color changes in the oral mucosa can be attributed to the deposition of either endogenous or exogenous pigments as a result of various mucosal diseases. The various pigmentations can be in the form of blue/purple vascular lesions, brown melanotic lesions, brown heme-associated lesions, gray/black pigmentations. PMID:26538887

  17. Re-exploring promising ?-glucosidase inhibitors for potential development into oral anti-diabetic drugs: Finding needle in the haystack.

    PubMed

    Ghani, Usman

    2015-10-20

    Treatment of diabetes mellitus by oral ?-glucosidase inhibitors is currently confined to acarbose, miglitol and voglibose marred by efficacy problems and unwanted side effects. Since the discovery of the drugs more than three decades ago, no significant progress has been made in the drug development area of anti-diabetic ?-glucosidase inhibitors. Despite existence of a wide chemical diversity of ?-glucosidase inhibitors identified to date, majority of them are simply piled up in publications and reports thus creating a haystack destined to be forgotten in the scientific literature without given consideration for further development into drugs. This review finds those "needles" in that haystack and lays groundwork for highlighting promising ?-glucosidase inhibitors from the literature that may potentially become suitable candidates for pre-clinical or clinical trials while drawing attention of the drug development community to consider and take already-identified promising ?-glucosidase inhibitors into the next stage of drug development. PMID:26344912

  18. Two-year survival of patients screened for transcatheter aortic valve replacement with potentially malignant incidental findings in initial body computed tomography

    PubMed Central

    Stachon, Peter; Kaier, Klaus; Milde, Simone; Pache, Gregor; Sorg, Stefan; Siepe, Matthias; von zur Mühlen, Constantin; Zirlik, Andreas; Beyersdorf, Friedhelm; Langer, Mathias; Zehender, Manfred; Bode, Christoph; Reinöhl, Jochen

    2015-01-01

    Aims Recently, transcatheter aortic valve replacement (TAVR) has evolved as the standard treatment in patients with inoperable aortic valve stenosis. According to TAVR guidelines, body computed tomography (CT) is recommended for pre-procedural planning. Due to the advanced age of these patients, multiple radiological potentially malignant incidental findings (pmIFs) appear in this cohort. It is unknown how pmIFs influence the decision by the heart team to intervene and the mortality. Methods and results We evaluated in a retrospective single-centre observational study 414 participants screened for TAVR with dual-source CT between October 2010 and December 2012. pmIFs are common and appeared in 18.7% of all patients screened for TAVR. The decision to intervene by TAVR or surgical aortic valve replacement (SAVR) was made by an interdisciplinary heart team and the role of pmIF in decision-making and time to treatment with TAVR or SAVR was analysed, retrospectively. The appearance of a pmIF vs. no pmIF did not significantly influence therapeutic decisions [odds ratio (OR) 1.14; P = 0.835] or time to treatment (91 ± 152 vs. 61 ± 109 days, respectively). Several findings, which are highly suspicious for malignancy, were less likely associated with invasive treatment (OR 0.207; P = 0.046). Patient survival was evaluated for at least 2 years until January 2014. Two-year survival of patients after TAVR or SAVR, treated according to the heart team decision, was ?75% and independent from the presence of a non-severe (P = 0.923) or severe (P = 0.823) pmIF. Conclusion The study indicates that frequently occurring radiologic pmIF did not influence 2-year survival after a decision to intervene was made by an interdisciplinary heart team. PMID:25759083

  19. Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence

    PubMed Central

    Chaidos, Aristeidis; Caputo, Valentina

    2015-01-01

    Post-translational modifications of the nucleosomal histone proteins orchestrate chromatin organization and gene expression in normal and cancer cells. Among them, the acetylation of N-terminal histone tails represents the fundamental epigenetic mark of open structure chromatin and active gene transcription. The bromodomain and extra-terminal (BET) proteins are epigenetic readers which utilize tandem bromodomains (BRD) modules to recognize and dock themselves on the acetylated lysine tails. The BET proteins act as scaffolds for the recruitment of transcription factors and chromatin organizers required in transcription initiation and elongation. The recent discovery of small molecules capable of blocking their lysine-binding pocket is the first paradigm of successful pharmacological inhibition of epigenetic readers. JQ1 is a prototype benzodiazepine molecule and a specific BET inhibitor with antineoplastic activity both in solid tumours and haematological malignancies. The quinolone I-BET151 and the suitable for clinical development I-BET762 benzodiazepine were introduced in parallel with JQ1 and have also shown potent antitumour activity in preclinical studies. I-BET762 is currently being tested in early phase clinical trials, along with a rapidly growing list of other BET inhibitors. Unlike older epigenetic therapies, the study of BET inhibitors has offered substantial, context-specific, mechanistic insights of their antitumour activity, which will facilitate optimal therapeutic targeting in future. Here, we review the development of this novel class of epigenetic drugs, the biology of BET protein inhibition, the emerging evidence from preclinical work and early phase clinical studies and we discuss their potential role in the treatment of haematological malignancies. PMID:26137204

  20. Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence.

    PubMed

    Chaidos, Aristeidis; Caputo, Valentina; Karadimitris, Anastasios

    2015-06-01

    Post-translational modifications of the nucleosomal histone proteins orchestrate chromatin organization and gene expression in normal and cancer cells. Among them, the acetylation of N-terminal histone tails represents the fundamental epigenetic mark of open structure chromatin and active gene transcription. The bromodomain and extra-terminal (BET) proteins are epigenetic readers which utilize tandem bromodomains (BRD) modules to recognize and dock themselves on the acetylated lysine tails. The BET proteins act as scaffolds for the recruitment of transcription factors and chromatin organizers required in transcription initiation and elongation. The recent discovery of small molecules capable of blocking their lysine-binding pocket is the first paradigm of successful pharmacological inhibition of epigenetic readers. JQ1 is a prototype benzodiazepine molecule and a specific BET inhibitor with antineoplastic activity both in solid tumours and haematological malignancies. The quinolone I-BET151 and the suitable for clinical development I-BET762 benzodiazepine were introduced in parallel with JQ1 and have also shown potent antitumour activity in preclinical studies. I-BET762 is currently being tested in early phase clinical trials, along with a rapidly growing list of other BET inhibitors. Unlike older epigenetic therapies, the study of BET inhibitors has offered substantial, context-specific, mechanistic insights of their antitumour activity, which will facilitate optimal therapeutic targeting in future. Here, we review the development of this novel class of epigenetic drugs, the biology of BET protein inhibition, the emerging evidence from preclinical work and early phase clinical studies and we discuss their potential role in the treatment of haematological malignancies. PMID:26137204

  1. Oral amelanotic melanoma.

    PubMed

    Adisa, A O; Olawole, W O; Sigbeku, O F

    2012-06-01

    Malignant melanomas of the mucosal regions of the head and neck are extremely rare neoplasms accounting for less than 1% of all melanomas. Approximately half of all head and neck melanomas occur in the oral cavity. Less than 2% of all melanomas lack pigmentation, in the oral mucosa however, up to 75% of cases are amelanotic. No etiologic factors or risk factors have been recognized for oral melanomas. Some authors have suggested that oral habits and selfmedication may be of etiological significance. Oral melanoma is rare but it is relatively frequent in countries like Japan, Uganda, and India. It is rarely identified under the age of 20 years. In Australia where cutaneous melanomas are relatively common primary melanoma of the oral mucosa is rare. The surface architecture of oral melanomas ranges from macular to ulcerated and nodular. The lesion is said to be asymptomatic in the early stages but may become ulcerated and painful in advanced lesions. The diagnosis of amelanotic melanoma is more difficult than that of pigmented lesions. The neoplasm consists of spindle-shaped cells with many mitotic figures and no cytoplasmic melanin pigmentation. Immunohistochemistry using S-100, HMB-45, Melan-A and MART-1 will help in establishing the correct diagnosis. Radical surgery with ample margins and adjuvant chemotherapy are appropriate management protocol for malignant melanoma. Oral melanoma is associated with poor prognosis but its amelanotic variant has even worse prognosis because it exhibits a more aggressive biology and because of difficulty in diagnosis which leads to delayed treatment. PMID:25161399

  2. Oral vaccines

    PubMed Central

    Zhu, Qing; Berzofsky, Jay A.

    2013-01-01

    Oral vaccines are safe and easy to administer and convenient for all ages. They have been successfully developed to protect from many infectious diseases acquired through oral transmission. We recently found in animal models that formulation of oral vaccines in a nanoparticle-releasing microparticle delivery system is a viable approach for selectively inducing large intestinal protective immunity against infections at rectal and genital mucosae. These large-intestine targeted oral vaccines are a potential substitute for the intracolorectal immunization, which has been found to be effective against rectogenital infections but is not feasible for mass vaccination. Moreover, the newly developed delivery system can be modified to selectively target either the small or large intestine for immunization and accordingly revealed a regionalized immune system in the gut. Future applications and research endeavors suggested by the findings are discussed. PMID:23493163

  3. Zinc finger X-chromosomal protein (ZFX) is a significant prognostic indicator and promotes cellular malignant potential in gallbladder cancer.

    PubMed

    Weng, Hao; Wang, Xu'an; Li, Maolan; Wu, Xiangsong; Wang, Zheng; Wu, Wenguang; Zhang, Zhou; Zhang, Yijian; Zhao, Shuai; Liu, Shibo; Mu, Jiasheng; Cao, Yang; Shu, Yijun; Bao, Runfa; Zhou, Jian; Lu, Jianhua; Dong, Ping; Gu, Jun; Liu, Yingbin

    2015-01-01

    The Zinc finger X-chromosomal protein (ZFX), a novel member of the Krueppel C2H2-type zinc finger protein family, has been implicated in multiple human cancers. However, the clinical significance of ZFX expression in gallbladder cancer (GBC) remains largely unknown. In this study, we focused on the clinical significance, biological function and mechanism of ZFX in GBC, and found that ZFX protein overexpression was frequently detected in GBC tissues. The expression of ZFX was significantly correlated with histological grade, perineural invasion, and margin status and lead to a significantly poorer prognosis in GBC patients(P <0.001). Furthermore, knockdown of ZFX result in significant inhibition of proliferation, migration, invasion and cause cell cycle arrest in GBC-SD cells, while over-expression of ZFX in NOZ shows the opposite results. Activation of PI3K/AKT pathway maybe the potential mechanism behind these effects. In conclusion, ZFX may serve as a oncogene and could be used as a potential prognostic marker and genetic treatment target for GBC patients. PMID:26230915

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

    PubMed Central

    Haverman, T. M.; Raber-Durlacher, J. E.; Rademacher, W. M. H.; Vokurka, S.; Epstein, J. B.; Huisman, C.; Hazenberg, M. D.; de Soet, J. J.; de Lange, J.; Rozema, F. R.

    2014-01-01

    Hematopoietic stem cell transplantation (HSCT) is widely used as a potentially curative treatment for patients with various hematological malignancies, bone marrow failure syndromes, and congenital immune deficiencies. The prevalence of oral complications in both autologous and allogeneic HSCT recipients remains high, despite advances in transplant medicine and in supportive care. Frequently encountered oral complications include mucositis, infections, oral dryness, taste changes, and graft versus host disease in allogeneic HSCT. Oral complications are associated with substantial morbidity and in some cases with increased mortality and may significantly affect quality of life, even many years after HSCT. Inflammatory processes are key in the pathobiology of most oral complications in HSCT recipients. This review article will discuss frequently encountered oral complications associated with HSCT focusing on the inflammatory pathways and inflammatory mediators involved in their pathogenesis. PMID:24817792

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

    SciTech Connect

    Ahmed, Merina; Hansen, Vibeke N.; Harrington, Kevin J.; Nutting, Christopher M.

    2009-10-01

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

  6. Potential effects of dietary folate supplementation on oral carcinogenesis, development and progression.

    PubMed

    Kingsley, Karl

    2010-03-01

    Folates are associated with a variety of human health benefits, while folate deficiency has been identified as a potential risk factor for many health problems and cancers, due to its role in dysregulation of DNA synthesis, repair and methylation. The US Food and Drug Administration adopted requirements for folate fortification in some food products, which has resulted in an increase in mean dietary folate intake and a concomitant reduction in the incidence of adverse health effects associated with folate deficiency. This includes a significant reduction in the incidence of folate deficiency-associated birth defects, such as spina bifida. PMID:22435573

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

    SciTech Connect

    Fujii, Etsuko Kimura, Kazuya; Mizoguchi, Keiji; Kato, Atsuhiko; Takanashi, Hisanori; Itoh, Zen; Omura, Satoshi; Suzuki, Masami

    2008-04-01

    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.

  8. Vemurafenib: targeted inhibition of mutated BRAF for treatment of advanced melanoma and its potential in other malignancies.

    PubMed

    Sharma, Anant; Shah, Sachin R; Illum, Henrik; Dowell, Jonathan

    2012-12-01

    Vemurafenib is the first molecularly targeted therapy to be licensed in the US and Europe for treatment of advanced melanoma. Its mechanism of action involves selective inhibition of the mutated BRAF V600E kinase that leads to reduced signalling through the aberrant mitogen-activated protein kinase (MAPK) pathway. Its efficacy is restricted to melanomas carrying the BRAF V600E mutation, which is seen in approximately 50% of all melanomas. In a randomized phase III trial, it was superior to dacarbazine in first-line treatment of advanced melanoma, with an overall response rate (ORR) of 48% (95% CI 42, 45), an estimated 6-month progression-free survival (PFS) of 5.3 versus 1.6 months (hazard ratio [HR] 0.26; 95% CI 0.20, 0.33; p?potential to enhance cell growth, proliferation and survival. Clinical trials to test the efficacy of vemurafenib in combination with immunomodulatory agents, such as ipilimumab, and MAPK kinase (MEK) inhibitors, such as GDC-0973, in the treatment of advanced melanoma are currently underway. Also under investigation is the use of vemurafenib in other solid tumours with BRAF mutations, such as papillary thyroid cancer. PMID:23116250

  9. 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

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

    2001-01-01

    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

  10. Radiopharmacological characterization of (64)Cu-labeled ?-MSH analogs for potential use in imaging of malignant melanoma.

    PubMed

    Gao, Feng; Sihver, Wiebke; Jurischka, Christoph; Bergmann, Ralf; Haase-Kohn, Cathleen; Mosch, Birgit; Steinbach, Jörg; Carta, Davide; Bolzati, Cristina; Calderan, Andrea; Pietzsch, Jens; Pietzsch, Hans-Jürgen

    2016-03-01

    The melanocortin-1 receptor (MC1R) plays an important role in melanoma growth, angiogenesis and metastasis, and is overexpressed in melanoma cells. ?-Melanocyte stimulating hormone (?-MSH) and derivatives are known to bind with high affinity at this receptor that provides the potential for selective targeting of melanoma. In this study, one linear ?-MSH-derived peptide Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH2 (NAP-NS1) without linker and with ?Ahx-?-Ala linker, and a cyclic ?-MSH derivative, [Lys-Glu-His-D-Phe-Arg-Trp-Glu]-Arg-Pro-Val-NH2 (NAP-NS2) with ?Ahx-?-Ala linker were conjugated with p-SCN-Bn-NOTA and labeled with (64)Cu. Radiochemical and radiopharmacological investigations were performed with regard to transchelation, stability, lipophilicity and in vitro binding assays as well as biodistribution in healthy rats. No transchelation reactions, but high metabolic stability and water solubility were demonstrated. The linear derivatives showed higher affinity than the cyclic one. [(64)Cu]Cu-NOTA-?Ahx-?-Ala-NAP-NS1 ([(64)Cu]Cu-2) displayed rapid cellular association and dissociation in murine B16F10 cell homogenate. All [(64)Cu]Cu-labeled conjugates exhibited affinities in the low nanomolar range in B16F10. [(64)Cu]Cu-2 showed also high affinity in human MeWo and TXM13 cell homogenate. In vivo studies suggested that [(64)Cu]Cu-2 was stable, with about 85 % of intact peptide in rat plasma at 2 h p.i. Biodistribution confirmed the renal pathway as the major elimination route. The uptake of [(64)Cu]Cu-2 in the kidney was 5.9 % ID/g at 5 min p.i. and decreased to 2.0 % ID/g at 60 min p.i. Due to the prospective radiochemical and radiopharmacological properties of the linear ?-MSH derivative [(64)Cu]Cu-2, this conjugate is a promising candidate for tracer development in human melanoma imaging. PMID:26643502

  11. Malignant hyperthermia.

    PubMed

    Kim, Dong-Chan

    2012-11-01

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

  12. Autofluorescence imaging in recurrent oral squamous cell carcinoma.

    PubMed

    Scheer, Martin; Fuss, Juliana; Derman, Mehmet Ali; Kreppel, Matthias; Neugebauer, Jörg; Rothamel, Daniel; Drebber, Uta; Zoeller, Joachim E

    2016-03-01

    The survival of patients with oral cancer is decreased by locoregional recurrence after an initial multimodal treatment. In order to identify lesions in the oral cavity for a possible recurrence, clinical evaluation as well as MRI or CT scanning is advised. The evaluation of mucosa lesions is hampered by changes related to radio- and chemotherapy as well as reconstruction with tissue flaps. Several techniques for easier identification of tissue abnormalities in the oral cavity have been advocated as adjuncts in order to facilitate identification. Especially methods using altered tissue fluorescence have gained much interest during the last decade. The aim of our prospective study was to evaluate fluorescence properties of undiagnosed mucosa lesions with the VELscope device in patients with multimodal treated oral cancer prior to histological confirmation. In total, 41 patients with a history of oral squamous cell carcinomas (OSCC) (19 females and 22 males) with undiagnosed mucosa lesions where included in the study. After clinical evaluation, examination and documentation using the VELscope® device were performed. Then, an incisional biopsy was performed. An autofluorescence loss indicating a malignant or dysplastic mucosa condition could be detected in six patients (14.6 %); however, only one OSCC and one SIN revealed a complete autofluorescence loss. In four patients, OSCC was present in lesions with retained autofluorescence. Sensitivity and specificity for the VELscope® examination to identify malignant oral lesions by autofluorescence were 33.3 and 88.6 %, respectively. The positive and negative predictive values were 33.3 and 88.6 %, respectively. No statistical correlation between gender and lesion appearance versus autofluorescence loss could be detected. In contrast to mucosa lesions in patients with no prior treatment, the autofluorescence evaluation with the VELscope reveals no additional information in our analysis. Accordingly, invasive biopsies as gold standard are still needed to get sufficient evidence regarding potential malignancy in patients after multimodal treatment for oral cancer. PMID:26267490

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

    SciTech Connect

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

    1983-06-30

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

  14. Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

    PubMed Central

    Tanaka, Takuji; Tanaka, Mayu; Tanaka, Takahiro

    2011-01-01

    Oral cancer is one of the major global threats to public health. The development of oral cancer is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are possible to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will yield important advances for detecting high-risk patients, monitoring preventive interventions, and assessing cancer risk and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from studies using appropriate animal carcinogenesis models. New approaches, such as molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy. PMID:21660266

  15. Verrucous Carcinoma with Oral Submucous Fibrosis: A Rare Case with Brief Review

    PubMed Central

    Komal, Khot; Deshmukh, Anjum

    2015-01-01

    Oral verrucous carcinoma (VC) is a variant of well differentiated oral squamous cell carcinoma (OSCC) characterized by exophytic over growth. Oral submucous fibrosis (OSMF) is a potentially malignant disorder associated with chronic betel nut chewing habit. The development of OSCC is seen in one-third of the OSMF patients, but the development of VC is rare in such patients. There are very few cases of OSMF with VC reported in literature. Here, present a rare case of an elderly patient with VC in conjunction with OSMF. PMID:26468468

  16. Techniques for early diagnosis of oral squamous cell carcinoma: Systematic review

    PubMed Central

    Carreras-Torras, Clàudia

    2015-01-01

    Background and objectives The diagnosis of early oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC) is of paramount clinical importance given the mortality rate of late stage disease. The aim of this study is to review the literature to assess the current situation and progress in this area. Material and Methods A search in Cochrane and PubMed (January 2006 to December 2013) has been used with the key words “squamous cell carcinoma”, “early diagnosis” “oral cavity”, “Potentially Malignant Disorders” y “premalignant lesions”. The inclusion criteria were the use of techniques for early diagnosis of OSCC and OPMD, 7 years aged articles and publications written in English, French or Spanish. The exclusion criteria were case reports and studies in other languages. Results Out of the 89 studies obtained initially from the search 60 articles were selected to be included in the systematic review: 1 metaanalysis, 17 systematic reviews, 35 prospective studies, 5 retrospective studies, 1 consensus and 1 semi-structured interviews. Conclusions The best diagnostic technique is that which we have sufficient experience and training. Definitely tissue biopsy and histopathological examination should remain the gold standard for oral cancer diagnose. In this systematic review it has not been found sufficient scientific evidence on the majority of proposed techniques for early diagnosis of OSCC, therefore more extensive and exhaustive studies are needed. Key words: Squamous cell carcinoma, early diagnosis, oral cavity, potentially malignant disorders, premalignant lesions. PMID:25662554

  17. Acquired hemophilia in malignancy.

    PubMed

    Reeves, Brandi N; Key, Nigel S

    2012-04-01

    Acquired hemophilia is a rare but potentially morbid complication in patients with cancer. It may be seen in patients with hematologic neoplasms (usually lymphoproliferative disorders) or with solid tumors. Although the presence of an underlying malignancy portends a worse outcome, the literature suggests that the usual principles of treatment, including immunosuppression, apply to these patients. However, appropriate consideration should be given to the choice of agents, depending on individual risk factors for complications such as thrombosis and infection. PMID:22682137

  18. Mutation of ERBB2 provides a novel alternative mechanism for the ubiquitous activation of RAS-MAPK in ovarian serous low malignant potential tumors.

    PubMed

    Anglesio, Michael S; Arnold, Jeremy M; George, Joshy; Tinker, Anna V; Tothill, Richard; Waddell, Nic; Simms, Lisa; Locandro, Bianca; Fereday, Sian; Traficante, Nadia; Russell, Peter; Sharma, Raghwa; Birrer, Michael J; deFazio, Anna; Chenevix-Trench, Georgia; Bowtell, David D L

    2008-11-01

    Approximately, 10% to 15% of serous ovarian tumors fall into the category designated as tumors of low malignant potential (LMP). Like their invasive counterparts, LMP tumors may be associated with extraovarian disease, for example, in the peritoneal cavity and regional lymph nodes. However, unlike typical invasive carcinomas, patients generally have a favorable prognosis. The mutational profile also differs markedly from that seen in most serous carcinomas. Typically, LMP tumors are associated with KRAS and BRAF mutations. Interrogation of expression profiles in serous LMP tumors suggested overall redundancy of RAS-MAPK pathway mutations and a distinct mechanism of oncogenesis compared with high-grade ovarian carcinomas. Our findings indicate that activating mutation of the RAS-MAPK pathway in serous LMP may be present in >70% of cases compared with approximately 12.5% in serous ovarian carcinomas. In addition to mutations of KRAS (18%) and BRAF (48%) mutations, ERBB2 mutations (6%), but not EGFR, are prevalent among serous LMP tumors. Based on the expression profile signature observed throughout our serous LMP cohort, we propose that RAS-MAPK pathway activation is a requirement of serous LMP tumor development and that other activators of this pathway are yet to be defined. Importantly, as few nonsurgical options exist for treatment of recurrent LMP tumors, therapeutic targeting of this pathway may prove beneficial, especially in younger patients where maintaining fertility is important. PMID:19010816

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

    PubMed Central

    Puri, Kamal D.; Gold, Michael R.

    2012-01-01

    The delta isoform of the p110 catalytic subunit (p110δ) of phosphoinositide 3-kinase is expressed primarily in hematopoietic cells and plays an essential role in B-cell development and function. Studies employing mice lacking a functional p110δ protein, as well as the use of highly-selective chemical inhibitors of p110δ, have revealed that signaling via p110δ-containing PI3K complexes (PI3Kδ) is critical for B-cell survival, migration, and activation, functioning downstream of key receptors on B cells including the B-cell antigen receptor, chemokine receptors, pro-survival receptors such as BAFF-R and the IL-4 receptor, and co-stimulatory receptors such as CD40 and Toll-like receptors (TLRs). Similarly, this PI3K isoform plays a key role in the survival, proliferation, and dissemination of B-cell lymphomas. Herein we summarize studies showing that these processes can be inhibited in vitro and in vivo by small molecule inhibitors of p110δ enzymatic activity, and that these p110δ inhibitors have shown efficacy in clinical trials for the treatment of several types of B-cell malignancies including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). PI3Kδ also plays a critical role in the activation, proliferation, and tissue homing of self-reactive B cells that contribute to autoimmune diseases, in particular innate-like B-cell populations such as marginal zone (MZ) B cells and B-1 cells that have been strongly linked to autoimmunity. We discuss the potential utility of p110δ inhibitors, either alone or in combination with B-cell depletion, for treating autoimmune diseases such as lupus, rheumatoid arthritis, and type 1 diabetes. Because PI3Kδ plays a major role in both B-cell-mediated autoimmune inflammation and B-cell malignancies, PI3Kδ inhibitors may represent a promising therapeutic approach for treating these diseases. PMID:22936933

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

    PubMed Central

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

    2011-01-01

    Background Late complications of allogeneic hematopoietic stem cell transplantation (HSCT) include a risk of secondary malignancies, including oral cancers. Optimization of best clinical practices for early diagnosis and treatment of oral premalignant or malignant lesions requires an assessment of potential predisposing risk factors as well as treatment outcomes. Methods The medical records of patients who developed oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) following allogeneic HSCT were reviewed. Data on demographics, HSCT course, chronic graft-versus-host disease (cGVHD), smoking and alcohol consumption, oral lesion characteristics, mode of therapy and clinical outcome were recorded; landmark survival was calculated. Results Twenty-six patients with OED (n = 8) and OSCC (n = 18) were identified with a median follow-up of 26.5 and 21.5 months, respectively. Premalignant and malignant oral lesions were diagnosed at a median time of 2.5 and 8 years after HSCT, respectively. Chronic GVHD was present in 96% of patients and of these, 96% had oral involvement. Multifocal oral cancer was found in 28% of cases, and localized recurrence was observed in 44% of cases. Five-year overall survival was 75% and 70% for OED and OSCC, respectively. Conclusions These results suggest that oral cGVHD may be considered a potential risk factor for the development of OSCC following allogeneic HSCT. The observation that oral cancers were frequently multifocal and recurred locally supports the concept of field cancerization and suggests that these cancers may be more aggressive compared with the non-HSCT population. Vigilant follow-up and coordination of care between hematologists and oral health specialists are critical to minimize morbidity and mortality. PMID:21460866

  1. The oral health consequences of chewing areca nut.

    PubMed

    Trivedy, C R; Craig, G; Warnakulasuriya, S

    2002-01-01

    Deleterious effects of areca nut on oral soft tissues are published extensively in the dental literature. Its effects on dental caries and periodontal tissues, two major oral diseases, are less well researched. Areca-induced lichenoid lesions mainly on buccal mucosa or tongue are reported at quid retained sites. In chronic chewers a condition known as betel chewer's mucosa, a discoloured areca nut-encrusted change, is often found where the quid particles are retained. Areca nut chewing is implicated in oral leukoplakia and submucous fibrosis, both of which are potentially malignant in the oral cavity. Oral cancer often arises from such precancerous changes in Asian populations. In 1985 the International Agency for Research on Cancer concluded that there is limited evidence to conclude that areca chewing may directly lead to oral cancer. There is, however, new information linking oral cancer to pan chewing without tobacco, suggesting a strong cancer risk associated with this habit. Public health measures to quit areca use are recommended to control disabling conditions such as submucous fibrosis and oral cancer among Asian populations. PMID:11900631

  2. Malignant hyperthermia.

    PubMed

    Bandschapp, Oliver; Girard, Thierry

    2012-01-01

    Malignant hyperthermia (MH) is a subclinical myopathy, usually triggered by volatile anaesthetics and depolarising muscle relaxants. Clinical symptoms are variable, and the condition is sometimes difficult to identify. Nevertheless, rapid recognition and specific as well as symptomatic treatment are crucial to avoid a lethal outcome. Molecular genetic investigations have confirmed the skeletal muscle type ryanodine receptor to be the major MH locus with more than 70% of MH families carrying a mutation in this gene. There is no screening method to test for MH, as current tests are invasive (open muscle biopsy) or restricted to MH families with known MH-associated mutations (molecular genetic testing). The prevalence of the MH trait is unknown, because the clinical penetrance after contact with triggering agents is very variable. More recently, MH mutations have been associated with rhabdomyolysis following statin therapy or with non-pharmacological triggering, such as exertional heat stroke. PMID:22851008

  3. Malignant mesothelioma

    PubMed Central

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

    2013-01-01

    Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor of the pleura and peritoneum with limited knowledge of its natural history. The incidence has increased in the past two decades but still it is a rare tumor. Etiology of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen. Mesothelioma is an insidious neoplasm arising from mesothelial surfaces i.e., pleura (65%-70%), peritoneum (30%), tunica vaginalis testis, and pericardium (1%-2%). The diagnosis of peritoneal and Pleural mesothelioma is often delayed, due to a long latent period between onset and symptoms and the common and nonspecific clinical presentation. The definite diagnosis can only be established by diagnostic laparoscopy or open surgery along with biopsy to obtain histological examination and immunocytochemical analysis. Different treatment options are available but Surgery can achieve a complete or incomplete resection and Radical resection is the preferred treatment. Chemotherapy has an important role in palliative treatment. Photodynamic therapy is also an option under trial. Patients who successfully underwent surgical resection had a considerably longer median survival as well as a significantly higher 5-year survival. Source of Data/Study Selection: The data were collected from case reports, cross-sectional studies, Open-label studies and phase –II trials between 1973-2012. Data Extraction: Web sites and other online resources of American college of surgeons, Medline, NCBI and Medscape resource centers were used to extract data. Conclusion: Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor with limited knowledge of its natural history. The diagnosis of peritoneal and Pleural mesothelioma is often delayed, so level of index of suspicion must be kept high. PMID:24550969

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

    NASA Astrophysics Data System (ADS)

    Kato, Shinya; Kimura, Masatsugu; Miwa, Nobuhiko

    2014-04-01

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

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

    PubMed Central

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

    2011-01-01

    Background The aim of this study was to investigate the intestinal mucus-penetrating properties and intestinal cellular uptake of two types of liposomes modified by Pluronic F127 (PF127). Methods The two types of liposomes, ie, PF127-inlaid liposomes and PF127-adsorbed liposomes, were prepared by a thin-film hydration method followed by extrusion, in which coumarin 6 was loaded as a fluorescence marker. A modified Franz diffusion cell mounted with the intestinal mucus of rats was used to study the diffusion characteristics of the two types of PF127 liposomes. Cell uptake studies were conducted in Caco-2 cells and analyzed using confocal laser scanning microcopy as well as flow cytometry. Results The diffusion efficiency of the two types of PF127-modified liposomes through intestinal rat mucus was 5–7-fold higher than that of unmodified liposomes. Compared with unmodified liposomes, PF127-inlaid liposomes showed significantly higher cellular uptake of courmarin 6. PF127-adsorbed liposomes showed a lower cellular uptake. Moreover, and interestingly, the two types of PF127-modified liposomes showed different cellular uptake mechanisms in Caco-2 cells. Conclusion PF127-inlaid liposomes with improved intestinal mucus-penetrating ability and enhanced cellular uptake might be a potential carrier candidate for oral drug delivery. PMID:22163166

  6. Positive/negative surface charge of chitosan based nanogels and its potential influence on oral insulin delivery.

    PubMed

    Wang, Juan; Xu, Mengxue; Cheng, Xiaojie; Kong, Ming; Liu, Ya; Feng, Chao; Chen, Xiguang

    2016-01-20

    To develop insulin delivery system for the treatment of diabetes, two insulin-loaded nanogels with opposite zeta potential (-15.94 ± 0.449 mV for insulin:CMCS/CS-NGs(-) and +17.15 ± 0.492 mV for insulin:CMCS/CS-NGs(+)) were obtained. Ex vivo results showed that the nanogels with opposite surface charge exhibited different adhesion and permeation in specific intestinal segments. There was no significant differences in adhesion and permeation in rat duodenum, but in rat jejunum, insulin:CMCS/CS-NGs(-) exhibited enhanced adhesion and permeation, which were about 3 folds (adhesion) and 1.7 folds (permeation) higher than insulin:CMCS/CS-NGs(+). These results demonstrated that the surface charge property of nanogels determined the absorption sites of CMCS/CS-NGs in small intestine. In vivo study, the blood glucose level in insulin:CMCS/CS-NGs(-) group had 3 mmol/L lower than insulin:CMCS/CS-NGs(+) group during 1h to 11h after the oral administration, which demonstrated that negative insulin:CMCS/CS-NGs had a better management of blood glucose than positive ones. PMID:26572423

  7. Oral curcumin mitigates the clinical and neuropathologic phenotype of the Trembler-J mouse: a potential therapy for inherited neuropathy.

    PubMed

    Khajavi, Mehrdad; Shiga, Kensuke; Wiszniewski, Wojciech; He, Feng; Shaw, Chad A; Yan, Jiong; Wensel, Theodore G; Snipes, G Jackson; Lupski, James R

    2007-09-01

    Mutations in myelin genes cause inherited peripheral neuropathies that range in severity from adult-onset Charcot-Marie-Tooth disease type 1 to childhood-onset Dejerine-Sottas neuropathy and congenital hypomyelinating neuropathy. Many myelin gene mutants that cause severe disease, such as those in the myelin protein zero gene (MPZ) and the peripheral myelin protein 22 gene (PMP22), appear to make aberrant proteins that accumulate primarily within the endoplasmic reticulum (ER), resulting in Schwann cell death by apoptosis and, subsequently, peripheral neuropathy. We previously showed that curcumin supplementation could abrogate ER retention and aggregation-induced apoptosis associated with neuropathy-causing MPZ mutants. We now show reduced apoptosis after curcumin treatment of cells in tissue culture that express PMP22 mutants. Furthermore, we demonstrate that oral administration of curcumin partially mitigates the severe neuropathy phenotype of the Trembler-J mouse model in a dose-dependent manner. Administration of curcumin significantly decreases the percentage of apoptotic Schwann cells and results in increased number and size of myelinated axons in sciatic nerves, leading to improved motor performance. Our findings indicate that curcumin treatment is sufficient to relieve the toxic effect of mutant aggregation-induced apoptosis and improves the neuropathologic phenotype in an animal model of human neuropathy, suggesting a potential therapeutic role in selected forms of inherited peripheral neuropathies. PMID:17701891

  8. Oral Curcumin Mitigates the Clinical and Neuropathologic Phenotype of the Trembler-J Mouse: A Potential Therapy for Inherited Neuropathy

    PubMed Central

    Khajavi, Mehrdad ; Shiga, Kensuke ; Wiszniewski, Wojciech ; He, Feng ; Shaw, Chad A. ; Yan, Jiong ; Wensel, Theodore G. ; Snipes, G. Jackson ; Lupski, James R. 

    2007-01-01

    Mutations in myelin genes cause inherited peripheral neuropathies that range in severity from adult-onset Charcot-Marie-Tooth disease type 1 to childhood-onset Dejerine-Sottas neuropathy and congenital hypomyelinating neuropathy. Many myelin gene mutants that cause severe disease, such as those in the myelin protein zero gene (MPZ) and the peripheral myelin protein 22 gene (PMP22), appear to make aberrant proteins that accumulate primarily within the endoplasmic reticulum (ER), resulting in Schwann cell death by apoptosis and, subsequently, peripheral neuropathy. We previously showed that curcumin supplementation could abrogate ER retention and aggregation-induced apoptosis associated with neuropathy-causing MPZ mutants. We now show reduced apoptosis after curcumin treatment of cells in tissue culture that express PMP22 mutants. Furthermore, we demonstrate that oral administration of curcumin partially mitigates the severe neuropathy phenotype of the Trembler-J mouse model in a dose-dependent manner. Administration of curcumin significantly decreases the percentage of apoptotic Schwann cells and results in increased number and size of myelinated axons in sciatic nerves, leading to improved motor performance. Our findings indicate that curcumin treatment is sufficient to relieve the toxic effect of mutant aggregation-induced apoptosis and improves the neuropathologic phenotype in an animal model of human neuropathy, suggesting a potential therapeutic role in selected forms of inherited peripheral neuropathies. PMID:17701891

  9. Giant Malignant Pheochromocytoma with Palpable Rib Metastases

    PubMed Central

    Gokce, Gokhan; Kilicli, Fatih; Elagoz, Sahande; Ayan, Semih; Gultekin, Emin Yener

    2014-01-01

    Pheochromocytoma is a rare and usually benign neuroendocrine neoplasm. Only 10% of all these tumors are malignant and there are no definitive histological or cytological criteria of malignancy. Single malignancy criteria are the presence of advanced locoregional disease or metastases. We report a case, with a giant retroperitoneal tumor having multiple metastases including palpable rib metastases, who was diagnosed as a malignant pheochromocytoma. The patient was treated with surgery. The literature was reviewed to evaluate tumor features and current diagnostic and therapeutic approaches for patients with metastatic or potentially malignant pheochromocytoma. PMID:25152826

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

    PubMed Central

    Sun, Hongwu; Liu, Kaiyun; Liu, Wei; Wang, Wenxiu; Guo, Chunliang; Tang, Bin; Gu, Jiang; Zhang, Jinyong; Li, Haibo; Mao, Xuhu; Zou, Quanming; Zeng, Hao

    2012-01-01

    Background: The stability of protein drugs remains one of the key hurdles to their success in the market. The aim of the present study was to design a novel nanoemulsion drug-delivery system (NEDDS) that would encapsulate a standard-model protein drug – bovine serum albumin (BSA) – to improve drug stability. Methods: The BSA NEDDS was prepared using a phase-inversion method and pseudoternary phase diagrams. The following characteristics were studied: morphology, size, zeta potential, drug loading, and encapsulation efficiency. We also investigated the stability of the BSA NEDDS, bioactivity of BSA encapsulated within the NEDDS, the integrity of the primary, secondary, and tertiary structures, and specificity. Results: The BSA NEDDS consisted of Cremophor EL-35, propylene glycol, isopropyl myristate, and normal saline. The average particle diameter of the BSA NEDDS was about 21.8 nm, and the system showed a high encapsulation efficiency (>90%) and an adequate drug-loading capacity (45 mg/mL). The thermodynamic stability of the system was investigated at different temperatures and pH levels and in room-temperature conditions for 180 days. BSA NEDDS showed good structural integrity and specificity for the primary, secondary, and tertiary structures, and good bioactivity of the loaded BSA. Conclusions: BSA NEDDS showed the properties of a good nanoemulsion-delivery system. NEDDS can greatly enhance the stability of the protein drug BSA while maintaining high levels of drug bioactivity, good specificity, and integrity of the primary, secondary, and tertiary protein structures. These findings indicate that the nanoemulsion is a potential formulation for oral administration of protein drugs. PMID:23118537

  11. Oral primary localized amyloidosis in HIV-infected patients: the oral face of a described skin lesion.

    PubMed

    Anaya-Saavedra, Gabriela; Ramírez-Amador, Velia; Valencia-Mayoral, Pedro

    2015-12-01

    Oral primary localized amyloidosis should be considered in the diagnosis of oral white lesions such as hyperplastic candidosis, lichen planus and lichenoid reactions; it is not associated with antiretroviral therapy use, systemic involvement or malignant transformation. PMID:25586447

  12. Oral insulin for diabetes prevention in NOD mice: potentiation by enhancing Th2 cytokine expression in the gut through bacterial adjuvant.

    PubMed

    Hartmann, B; Bellmann, K; Ghiea, I; Kleemann, R; Kolb, H

    1997-08-01

    Oral administration of insulin suppresses the development of diabetes in nonobese diabetic (NOD) mice and deviates the cytokine balance in the islets of Langerhans from a Th1 to a Th2 type cytokine pattern. However, the effect of oral insulin is limited and disease suppression is limited to a narrow dose range. Therefore we tried to improve the outcome of suboptimal insulin dosing by bacterial adjuvant. Mice treated with a suboptimal dose of oral insulin showed no change in diabetes incidence although a shift from Th1 towards Th2 cytokine expression occurred in inflamed islets. Significant suppression of diabetes development was only seen in NOD mice receiving both, insulin and the bacterial preparation OM-89 as adjuvant. OM-89 is a protein extract of Escherichia coli, with nonspecific immunostimulatory properties. Potentiation of the effect of oral insulin by the adjuvant was associated with upregulation of interleukin (IL)-4 Th2 cells in infiltrated islets and sustained local IL-2 gene expression. RT PCR analyses of cytokine expression in the gut showed a clear deviation to Th2 type reactivity and downregulation of inducible nitric oxide (NO) synthase (iNOS) expression by the bacterial adjuvant but not by oral insulin alone. Since macrophages are the primary target cells of adjuvant action we tested its effect on mouse macrophages in vitro. Treatment with OM-89 induced transient release of tumour necrosis factor alpha and nitrite but rendered macrophages refractory to restimulation by the potent macrophage activator lipopolysaccharide. In conclusion, the protective effect of oral insulin can be potentiated by pretreatment with the bacterial adjuvant OM-89. This effect correlates with enhanced Th2 cytokine and decreased iNOS gene expression in the gut, probably due to the downregulation of proinflammatory mediators by exposure to the adjuvant. PMID:9267984

  13. Epstein-Barr virus in oral diseases.

    PubMed

    Slots, J; Saygun, I; Sabeti, M; Kubar, A

    2006-08-01

    Epstein-Barr virus (EBV), a B-lymphotropic gamma-herpesvirus, causes infectious mononucleosis and oral hairy leukoplakia, and is associated with various types of lymphoid and epithelial malignancies. Saliva is the main vehicle for EBV transmission from individual to individual. Recent studies have also implicated EBV in the pathogenesis of advanced types of periodontal disease. EBV DNA is detected in 60-80% of aggressive periodontitis lesions and in 15-20% of gingivitis lesions or normal periodontal sites. The periodontal presence of EBV is associated with an elevated occurrence of periodontopathic anaerobic bacteria. Moreover, EBV active infection occurs in approximately 70% of symptomatic and large-size periapical lesions. EBV and cytomegalovirus often co-exist in marginal and apical periodontitis. Periodontal therapy can markedly suppress the EBV load in periodontal pockets as well as in saliva, which has the potential to reduce the risk of viral transmission between close individuals. EBV proteins up-regulate cytokines and growth factors, which seem to play a central role in the proliferative response of tongue epithelial cells in oral hairy leukoplakia and in the cell-transformation process of EBV-associated malignancies. Further research is needed to identify the full range of EBV-related diseases in the human oral cavity. PMID:16827715

  14. [Malignant melanoma].

    PubMed

    Champeau, F; Verola, O

    1998-08-01

    Malignant melanoma is the most serious skin tumor and its incidence is doubling every ten years. Ultraviolet rays represent the main environmental cause of melanoma. Among the constitutional factors identified, two clinicopathological forms of naevus are considered to be important epidemiological precursors: acquired dysplastic naevi and congenital giant naevi. Four clinical and histological types are distinguished: SSM (Superficial Spreading Melanoma), NM (Nodular Melanoma), LMM (Lentigo Maligna Melanoma), arising from Dubreuilh melanosis, ALM (Acral Lentiginous Melanoma). Thickness constitutes the essential prognostic factor. Clinical examination is the only recommended standard assessment. Chest x-ray is useful, and acts as a reference for subsequent follow-up. Other complementary investigations are requested as a function of clinical signs. Treatment is exclusively surgical. The lateral resection margins are 0.5 cm for melanoma in situ, 1 cm for melanomas less than 1 mm thick, 2 cm for melanomas between 1 and 4 mm thick, and 3 cm for melanomas thicker than 4 mm. Chemotherapy is mainly used in the treatment of metastatic melanoma. There is no indication for radiotherapy apart from palliative treatment of nonsurgical metastases. New therapies such as immunotherapy and gene therapy are under investigation. PMID:9926473

  15. EGFR/HER2 inhibitors effectively reduce the malignant potential of MDR breast cancer evoked by P-gp substrates in vitro and in vivo.

    PubMed

    Jin, Yiting; Zhang, Wei; Wang, Hongying; Zhang, Zijing; Chu, Chengyu; Liu, Xiuping; Zou, Qiang

    2016-02-01

    Multidrug resistance (MDR) induced by chemotherapy in breast cancer frequently leads to tumor invasion, metastasis and poor clinical outcome. We preliminarily found that the epidermal growth factor receptor (EGFR) is involved in enhancing the malignant potential of MDR breast cancer cells, but the mechanism remains unclear. In the present study, we demonstrated in vitro and in vivo that EGFR/HER2 promote the invasive and metastatic abilities of MDR breast cancer. More importantly, a new function of EGFR/HER2 inhibitors was revealed for the first time, which could improve the treatment efficacy of breast cancer by reversing the MDR process rather than by inhibiting tumor growth. Firstly, using quantitative real?time PCR and western blot analysis, we found that overexpression of EGFR/HER2 in MCF7/Adr cells upregulated CD147 and MMP2/9 at both the transcription and protein expression levels, which promoted tumor cell migration, as determined using an in vitro invasion assay. Secondly, the upregulated levels of CD147 and MMP2/9 were decreased when EGFR/HER2 activity was inhibited, and therefore tumor invasion was also significantly inhibited. These phenomena were also demonstrated in nude mouse assays. Additionally, in MDR breast cancer patients, we found that overexpression of EGFR and P?gp levels led to shorter overall survival (OS) and disease?free survival (DFS) by IHC assays and Kaplan?Meier survival analysis. In conclusion, EGFR/HER2 play a crucial role in enhancing CD147 and MMP expression to establish favorable conditions for invasion/metastasis in MDR breast cancer. The scope of application of EGFR/HER2 inhibitors may be expanded in EGFR/HER2?positive patients. We suggest that MDR breast cancer patients may benefit from novel therapies targeting EGFR/HER2. PMID:26718028

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

    PubMed Central

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

    2013-01-01

    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

  17. Recent developments on the significance and pathogenesis of lymph node involvement in ovarian serous tumors of low malignant potential (borderline tumors).

    PubMed

    Fadare, Oluwole

    2009-01-01

    In approximately 27% of patients that were surgically staged for ovarian serous borderline tumors (ovarian serous tumors of low malignant potential), regional lymph nodes, most commonly the pelvic and paraaortic groups, display morphologically similar epithelial clusters. Lymph nodes above the diaphragm may also be involved. Lymph node involvement does not adversely impact the overall survival of patients with ovarian serous borderline tumors, but there is controversy as to whether this finding is associated with a decrease in recurrence-free survival. Nodular aggregates of epithelium greater than 1 mm in maximum dimension, as compared with all other patterns of nodal involvement, have been associated with reduced recurrence-free survival. The lymph nodes may also be the site of recurrence and/or progression to carcinoma of an ovarian serous borderline tumor. Recent molecular and morphologic data suggest that although most nodal implants are indeed metastatic from their synchronous ovarian neoplasms, a small subset arise de novo from nodal endosalpingiosis. The precise mechanistic basis for how these noninvasive neoplasms achieve nodal metastases is unclear. However, because most patients with nodal metastases also have peritoneal implants, tumors that are ovary-confined and without ovarian surface involvement are rarely associated with nodal involvement, microinvasive borderline tumors frequently display lymphatic vessel involvement yet show a remarkably low frequency of nodal involvement, in conjunction with the recent finding that node-positive and node-negative tumors display no significant differences in lymphatic vessel density, suggest that the route of spread to lymph nodes in most cases is via the peritoneal and not tumoral lymphatics. PMID:19258950

  18. The serrated neoplasia pathway of colorectal tumors: Identification of MUC5AC hypomethylation as an early marker of polyps with malignant potential.

    PubMed

    Renaud, Florence; Mariette, Christophe; Vincent, Audrey; Wacrenier, Agnès; Maunoury, Vincent; Leclerc, Julie; Coppin, Lucie; Crépin, Michel; Van Seuningen, Isabelle; Leteurtre, Emmanuelle; Buisine, Marie-Pierre

    2016-03-15

    The serrated neoplasia pathway accounts for 20-30% of colorectal cancers (CRC), which are characterized by extensive methylation (CpG island methylation phenotype, CIMP), frequent BRAF mutation and high microsatellite instability (MSI). We recently identified MUC5AC mucin gene hypomethylation as a specific marker of MSI CRC. The early identification of preneoplastic lesions among serrated polyps is currently challenging. Here, we performed a detailed pathological and molecular analysis of a large series of colorectal serrated polyps and evaluated the usefulness of mucin genes MUC2 and MUC5AC to differentiate serrated polyps and to identify lesions with malignant potential. A series of 330 colorectal polyps including 218 serrated polyps [42 goblet cell-rich hyperplastic polyps (GCHP), 68 microvesicular hyperplastic polyps (MVHP), 100 sessile serrated adenoma (SSA) and eight traditional serrated adenoma (TSA)] and 112 conventional adenomas was analyzed for BRAF/KRAS mutations, MSI, CIMP, MLH1 and MGMT methylation, and MUC2 and MUC5AC expression and methylation. We show that MUC5AC hypomethylation is an early event in the serrated neoplasia pathway, and specifically detects MVHP and SSA, arguing for a filiation between MVHP, SSA and CIMP-H/MSI CRC, whereas GCHP and TSA arise from a distinct pathway. Moreover, MUC5AC hypomethylation specifically identified serrated lesions with BRAF mutation, CIMP-H or MSI, suggesting that it may be useful to identify serrated neoplasia pathway-related precursor lesions. Our data suggest that MVHP should be recognized among HP and require particular attention. PMID:26476272

  19. Recurrent papillary urothelial neoplasm of low malignant potential. Subtle architectural disorder detected by quantitative analysis in DAXX-immunostained tissue sections.

    PubMed

    Castellini, Paolo; Montironi, Maria A; Zizzi, Antonio; Scarpelli, Marina; Mazzucchelli, Roberta; Lopez-Beltran, Antonio; Cheng, Liang; Paone, Nicola; Montironi, Rodolfo

    2014-04-01

    The aim of the study was to identify subtle changes in the so-called architectural predominant order in nonrecurrent and recurrent papillary urothelial neoplasm of low malignant potential (PUNLMP). Quantitative analysis was performed with a software package written in LabVIEW (National Instruments, Austin, TX) in DAXX-immunostained tissue sections. Twelve cases of PUNLMP with papillary fronds sectioned lengthwise through the core were investigated and subdivided as follows: 7 nonrecurrent and 5 recurrent PUNLMP cases. Six cases of normal urothelium (NU) were included. When an epithelial thickness threshold is set at 108 ?m (ie, 400 pixels), there is a complete separation between NU and PUNLMP; however, nonrecurrent and recurrent cases fall in the same range of thickness. In setting a nuclear elongation factor threshold at 2.1, there are differences between the 2 PUNLMP groups, recurrent PUNLMP and NU cases, showing a somewhat similar proportion of elongated nuclei. The nuclear orientation separates nonrecurrent from recurrent PUNLMP groups; however, NU cases do not appear as a separate group from the 2 PUNLMP groups. In combining epithelial thickness, nuclear elongation, and orientation in a multivariate analysis, the 2 PUNLMP groups appear separate between them and from NU. NU is less thickened than the 2 PUNLMP groups and shows a combination of elongated and less elongated nuclei. Elongated nuclei are more numerous in nonrecurrent PUNLMP, whereas the nuclei in recurrent PUNLMP are less elongated and less polarized than in the other group. Such finding can be used routinely to identify those PUNLMP patients who will have recurrence. PMID:24565208

  20. Oral Lichenoid Lesions - A Review and Update

    PubMed Central

    Kamath, Venkatesh Vishwanath; Setlur, Krishnanand; Yerlagudda, Komali

    2015-01-01

    Background: Oral lichenoid lesions or reactions (OLLs/OLRs) are clinical and histological contemporaries of the classical oral lichen planus (OLP) that have generated a lot of debate in literature. In contrast to the idiopathic nature of OLP, OLLs are often associated with a known identifiable inciting factor. A superficial examination of these lesions clinically and histologically often reveals many similarities with OLP, but recent data indicate that distinguishable features do exist and form the basis of most classifications. Aims and Objectives: This paper attempts to collate available data in English literature on OLLs, highlight distinguishing features clinically and histologically and reflect on the malignant transformation potential and treatment modalities of the condition. Materials and Methods: A comprehensive search of medical and dental databases including PubMed, Ovid, Cochrane, Pubget, Researchgate, and non-medical search engines were utilized for the review. The search words included “oral lichen planus”, “oral lichenoid lesions”, “oral drug reactions”, “lichenoid dysplasia”, and “adverse effects of dental materials”. Review Results: OLLs seem to grossly underrated and most cases were clubbed as OLP. Definite clinical and histological features were uncovered to establish the identity of this lesion. Associations with dental restorative materials, drugs, and medications have been conclusively proven in the etiology of this condition. Specific markers are being utilized to diagnose the condition and monitor its progress. Conclusion: Substantial differentiating features were uncovered to delineate OLLs as a separate entity with definite etiology, pathogenesis, and a high malignant transformation rate compared with OLP. PMID:25657414

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

    PubMed

    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

    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

  2. In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria

    PubMed Central

    Suzuki, Shigeo; Hikosaka, Kenji; Balogun, Emmanuel O.; Komatsuya, Keisuke; Niikura, Mamoru; Kobayashi, Fumie; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo

    2015-01-01

    5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe2+) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug. PMID:26324278

  3. The R enantiomer of the antitubercular drug PA-824 as a potential oral treatment for visceral Leishmaniasis.

    PubMed

    Patterson, Stephen; Wyllie, Susan; Stojanovski, Laste; Perry, Meghan R; Simeons, Frederick R C; Norval, Suzanne; Osuna-Cabello, Maria; De Rycker, Manu; Read, Kevin D; Fairlamb, Alan H

    2013-10-01

    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

  4. In vivo curative and protective potential of orally administered 5-aminolevulinic acid plus ferrous ion against malaria.

    PubMed

    Suzuki, Shigeo; Hikosaka, Kenji; Balogun, Emmanuel O; Komatsuya, Keisuke; Niikura, Mamoru; Kobayashi, Fumie; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo; Kita, Kiyoshi

    2015-11-01

    5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe(2+)) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug. PMID:26324278

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

    PubMed Central

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

    2014-01-01

    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 α4β7 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

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

    PubMed Central

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

    2015-01-01

    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

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

    PubMed

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

    2015-02-01

    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

  8. Malignant hyperthermia

    PubMed Central

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

    2007-01-01

    Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane 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

  9. A phase contrast cytomorphometric study of squames of normal oral mucosa and oral leukoplakia: Original study

    PubMed Central

    Nadaf, Afreen; Bavle, Radhika M; Thambiah, Lalita J; Paremala, K; Sudhakara, M; Soumya, M

    2014-01-01

    Oral leukoplakia represents the most common potentially malignant oral disorder, representing 85% of such lesions. The worldwide prevalence of leukoplakia is 1.5- 4.3%. Leukoplakia is often associated with carcinogenic exposures, such as from use of tobacco, alcohol or betel nut. The level of risk for malignant transformation of leukoplakia is associated with lesion histology. The overall malignant transformation rates for dysplastic lesions range from 11% to 36%, depending on the length of follow-up. Exfoliative cytology is a simple and minimally invasive method. Phase contrast microscope, an essential tool in the field of biology and medical research provides improved discrimination of cellular details. Aims: To study and compare the cytomorphological and cytomorphometric features of squames obtained from the mucosa of normal individuals, tobacco habituates with and without clinically evident leukoplakia. To assess the role of phase contrast microscopy as an alternative and easy method of cytological evaluation of wet and unstained smears. Materials and Methods: Fifty cases from each group were taken. Fixed, unstained smears were viewed under phase contrast microscope and were evaluated morphologically and morphometrically for nuclear and cellular diameters. Results: The study showed a significant increase in the mean nuclear diameter and decrease in the mean cellular diameter. Conclusion: Cytomorphometric changes could be the earliest indicators of cellular alterations. This indicates that there could be a cause-effect relationship between tobacco and quantitative alterations. PMID:25364176

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

    PubMed

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

    2014-10-01

    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

  11. AGS67E, an Anti-CD37 Monomethyl Auristatin E Antibody–Drug Conjugate as a Potential Therapeutic for B/T-Cell Malignancies and AML: A New Role for CD37 in AML

    PubMed Central

    Pereira, Daniel S.; Guevara, Claudia I.; Jin, Liqing; Mbong, Nathan; Verlinsky, Alla; Hsu, Ssucheng J.; Aviña, Hector; Karki, Sher; Abad, Joseph D.; Yang, Peng; Moon, Sung-Ju; Malik, Faisal; Choi, Michael Y.; An, Zili; Morrison, Kendall; Challita-Eid, Pia M.; Doñate, Fernando; Joseph, Ingrid B.J.; Kipps, Thomas J.; Dick, John E.; Stover, David R.

    2015-01-01

    CD37 is a tetraspanin expressed on malignant B cells. Recently, CD37 has gained interest as a therapeutic target. We developed AGS67E, an antibody–drug conjugate that targets CD37 for the potential treatment of B/T-cell malignancies. It is a fully human monoclonal IgG2 antibody (AGS67C) conjugated, via a protease-cleavable linker, to the microtubule-disrupting agent mono-methyl auristatin E (MMAE). AGS67E induces potent cytotoxicity, apoptosis, and cell-cycle alterations in many non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) cell lines and patient-derived samples in vitro. It also shows potent antitumor activity in NHL and CLL xenografts, including Rituxan-refractory models. During profiling studies to confirm the reported expression of CD37 in normal tissues and B-cell malignancies, we made the novel discovery that the CD37 protein was expressed in T-cell lymphomas and in AML. AGS67E bound to >80% of NHL and T-cell lymphomas, 100% of CLL and 100% of AML patient-derived samples, including CD34+CD38? leukemic stem cells. It also induced cytotoxicity, apoptosis, and cell-cycle alterations in AML cell lines and antitumor efficacy in orthotopic AML xenografts. Taken together, this study shows not only that AGS67E may serve as a potential therapeutic for B/T-cell malignancies, but it also demonstrates, for the first time, that CD37 is well expressed and a potential drug target in AML. PMID:25934707

  12. Salivary Markers for Oral Cancer Detection

    PubMed Central

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

    2010-01-01

    Oral cancer refers to all malignancies that arise in the oral cavity, lips and pharynx, with 90% of all oral cancers being oral squamous cell carcinoma. Despite the recent treatment advances, oral cancer is reported as having one of the highest mortality ratios amongst other malignancies and this can much be attributed to the late diagnosis of the disease. Saliva has long been tested as a valuable tool for drug monitoring and the diagnosis systemic diseases among which oral cancer. The new emerging technologies in molecular biology have enabled the discovery of new molecular markers (DNA, RNA and protein markers) for oral cancer diagnosis and surveillance which are discussed in the current review. PMID:21673842

  13. Potential role of autophagy in smokeless tobacco extract-induced cytotoxicity and in morin-induced protection in oral epithelial cells.

    PubMed

    Ganguli, Arnab; Das, Amlan; Nag, Debasish; Bhattacharya, Surela; Chakrabarti, Gopal

    2016-04-01

    Toxic components of STE induced serious, adverse human oral health outcomes. In the present study, we observed that STE was involved in oral toxicity by reducing the viability of human squamous epithelial cells, SCC-25, along with the simultaneous induction of both apoptosis and autophagic signaling. STE was also found to induce significant amount ROS generation in SCC-25 cells. The dietary flavonoid morin, found abundantly in a variety of herbs, fruits and wine, has been reported to attenuate ROS-induced pathogenesis including autophagy. In this study we designed three different treatment regimes of morin treatment, such as pre, co, and post - treatment of STE challenged SCC-25 cells. In all cases morin provided cytoprotection to STE challenged SCC-25 cells by augmenting STE induced ROS-dependent cytotoxic autophagy. Hence, morin is a potential option for antioxidant therapy in treatment of STE induced toxicity. PMID:26891815

  14. A malignant itch.

    PubMed Central

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

    2006-01-01

    We report an unusual presentation of a previously healthy three-year-old Chinese girl with a four-week history of apparently unexplained generalized intense itch. She had no past history of atopy or xerosis. Despite the severe itch, she had only minimal scratch marks on her right gluteal region but no flexural involvement. The girl was treated as having scabies and eczema and with oral antihistamines by various dermatologists without much improvement. She subsequently presented to a regional hospital with right hip pain and fever. Radiological and histopathological investigations confirmed that she had a peripheral T-cell lymphoma. The itch pattern prior to and following chemotherapy, as documented by the DigiTrac wrist-held movement monitor, showed a dramatic reduction of her nocturnal itch. The pattern was also very different from that of atopic dermatitis in that the scratching was of much higher intensity but lower frequency. Intractable pruritus associated with a peripheral T-cell lymphoma has not been previously reported in the pediatric literature. This report serves to alert clinicians of the gold paradigm that in a patient with an unexplained generalized itch, lymphoma and other malignancies must be considered. Images Figure 1 Figure 2 Figure 3 PMID:17225848

  15. Mycological and histological associations of Candida in oral mucosal lesions.

    PubMed

    Hebbar, Pragati B; Pai, Anuradha; D, Sujatha

    2013-01-01

    The present study aimed to assess the presence and level of colonization of Candida in patients with oral mucosal lesions, to determine the presence or absence of candidal hyphae in biopsy specimens and to correlate the degree of epithelial dysplasia with the number of colony-forming units of Candida. We performed a prospective study including 50 patients diagnosed as having oral potentially malignant and malignant disorders. These patients had lesions such as leukoplakia, lichen planus, lichenoid reaction, verrucous carcinoma and oral squamous cell carcinoma. An oral swish with 10 mL of normal saline was performed, and this was collected in a sterile plastic container. Candidal colony-forming units were assessed in the specimen. This was followed by a biopsy of the lesion, which was sent for histopathologic examination for dysplasia and severity, and to assess the presence or absence of candidal hyphae. The results of the present study revealed a correlation between higher Candida colonization and increasing severity of dysplasia. An effort was made to correlate Candida by histologic and mycologic means with epithelial dysplasia. If such a correlation is strongly established, then the importance of antimycotic therapy can be emphasized to avoid deterioration. PMID:23748455

  16. Oral mucositis.

    PubMed

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

    2006-05-01

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

  17. [Soft tissue pathologies of the oral cavity].

    PubMed

    Margotta, V; Capogreco, M

    2003-01-01

    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

  18. Oral Herpes

    MedlinePLUS

    ... Search Text size: Website Contents NIDCR Home Oral Health Diseases and Conditions Gum Disease TMJ Disorders Oral Cancer Dry Mouth Burning Mouth Tooth Decay See All Oral Complications of Systemic Diseases Cancer Treatment Developmental Disabilities Diabetes Heart Disease ...

  19. Oral Cancer

    MedlinePLUS

    ... Search Text size: Website Contents NIDCR Home Oral Health Diseases and Conditions Gum Disease TMJ Disorders Oral Cancer Dry Mouth Burning Mouth Tooth Decay See All Oral Complications of Systemic Diseases Cancer Treatment Developmental Disabilities Diabetes Heart Disease ...

  20. Oral Warts

    MedlinePLUS

    ... Search Text size: Website Contents NIDCR Home Oral Health Diseases and Conditions Gum Disease TMJ Disorders Oral Cancer Dry Mouth Burning Mouth Tooth Decay See All Oral Complications of Systemic Diseases Cancer Treatment Developmental Disabilities Diabetes Heart Disease ...

  1. Oral myiasis.

    PubMed

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

    2015-01-01

    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

  2. Oral Myiasis

    PubMed Central

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

    2015-01-01

    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

  3. Lung Malignancies in HIV Infection.

    PubMed

    Sigel, Keith; Pitts, Robert; Crothers, Kristina

    2016-04-01

    Pulmonary malignancies are a major source of morbidity and mortality in HIV-infected persons. Non-AIDS-defining lung cancers (mostly non-small cell lung cancers) are now a leading cause of cancer death among HIV-infected persons. HIV-associated factors appear to affect the risk of lung cancer and may adversely impact cancer treatment and outcomes. HIV infection also may modify the potential harms and benefits of lung cancer screening with computed tomography. AIDS-defining lung malignancies include pulmonary Kaposi sarcoma and pulmonary lymphoma, both of which are less prevalent with widespread adoption of antiretroviral therapy. PMID:26974303

  4. Temozolomide for Treating Malignant Melanoma.

    PubMed

    Li, Rong-Hua; Hou, Xiao-Yang; Yang, Chun-Sheng; Liu, Wen-Lou; Tang, Jian-Qin; Liu, Yan-Qun; Jiang, Guan

    2015-09-01

    Melanoma is one of the most malignant forms of skin cancer; with a rapidly increasing prevalence. Early-stage melanoma is curable, but advanced metastatic melanoma is almost always fatal, and patients with such advanced disease have short median survival. Surgery and radiotherapy play a limited role in the treatment of metastatic melanoma. Rather, chemotherapy remains the mainstay of treatment, although other approaches, including biotherapy and gene therapy, have been attempted. The authors hereby, evaluated the use of temozolomide (TMZ) for treating metastatic melanoma compared to dacarbazine (DTIC), the effectiveness of TMZ for treating brain metastases, as well as TMZ resistance and how the efficacy of TMZ in malignant melanoma can be increased. Two chemotherapeutic regimens are commonly used for palliative treatment of malignant melanoma: intravenous administration of DTIC and oral administration of the alkylating agent temozolomide (TMZ). Compared to DTIC, TMZ is very well tolerated and has an advantage in terms of improving the quality of life of patients with metastatic melanoma. While the prognosis is currently unpromising, chemotherapy plays a palliative role for patients with metastatic melanoma. The toxicity of treatment regimens based on DTIC and TMZ do not differ significantly, although TMZ is costlier. These findings provide a reference for future researchers via a comprehensive analysis of the relevant literature. PMID:26374366

  5. Quantitative proteomic analysis of microdissected oral epithelium for cancer biomarker discovery.

    PubMed

    Xiao, Hua; Langerman, Alexander; Zhang, Yan; Khalid, Omar; Hu, Shen; Cao, Cheng-Xi; Lingen, Mark W; Wong, David T W

    2015-11-01

    Specific biomarkers are urgently needed for the detection and progression of oral cancer. The objective of this study was to discover cancer biomarkers from oral epithelium through utilizing high throughput quantitative proteomics approaches. Morphologically malignant, epithelial dysplasia, and adjacent normal epithelial tissues were laser capture microdissected (LCM) from 19 patients and used for proteomics analysis. Total proteins from each group were extracted, digested and then labelled with corresponding isobaric tags for relative and absolute quantitation (iTRAQ). Labelled peptides from each sample were combined and analyzed by liquid chromatography-mass spectrometry (LC-MS/MS) for protein identification and quantification. In total, 500 proteins were identified and 425 of them were quantified. When compared with adjacent normal oral epithelium, 17 and 15 proteins were consistently up-regulated or down-regulated in malignant and epithelial dysplasia, respectively. Half of these candidate biomarkers were discovered for oral cancer for the first time. Cornulin was initially confirmed in tissue protein extracts and was further validated in tissue microarray. Its presence in the saliva of oral cancer patients was also explored. Myoglobin and S100A8 were pre-validated by tissue microarray. These data demonstrated that the proteomic biomarkers discovered through this strategy are potential targets for oral cancer detection and salivary diagnostics. PMID:26321370

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

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

  7. Potential involvement of miR-375 in the premalignant progression of oral squamous cell carcinoma mediated via transcription factor KLF5

    PubMed Central

    Li, Siyuan; Shan, Xiaofeng; Liu, Xiaosong; Hua, Hong; Zhao, Chuanke; Feng, Zhendong; Cai, Zhigang; Zhang, Lihe; Zhou, Demin

    2015-01-01

    To elucidate the genetic effect involved in the premalignant progression of chronic inflammation to cancer, we performed microRNA and mRNA profiling in oral lichen planus (OLP), oral squamous cell carcinoma (OSCC), and normal tissue from the same patients. We demonstrate the involvement of a suppressive microRNA, miR-375, in the regulation of this premalignant progression via KLF5, a transcription factor that modulates the expression of genes contributing to proliferation and apoptosis. We found that miR-375 abundance decreased in tissues with progression from the normal state to OLP and subsequently to OSCC. Restoration of miR-375 by transduction of a synthetic mimic into OSCC cells repressed cellular proliferation and promoted apoptosis, with concomitant down-regulation of KLF5, and vice versa. The direct binding of miR-375 to the 3′-untranslated region of KLF5 was further confirmed. Additionally, Survivin (BIRC5), a target of KLF5, was also regulated by miR-375, explaining the susceptibility of miR-375-mimic transfected cells to apoptosis. Further analysis of clinical specimens suggested that expression of KLF5 and BIRC5 is up-regulated during the progression from inflammation to cancer. Our findings provide novel insights into the involvement of microRNAs in progression of inflammation to carcinoma and suggest a potential early-stage biomarker or therapy target for oral carcinoma. PMID:26474386

  8. Pediatric Salivary Gland Malignancies.

    PubMed

    Ord, Robert A; Carlson, Eric R

    2016-02-01

    Pediatric malignant salivary gland tumors are extremely rare. The percentage of malignant tumors is higher than that seen in adults, although the outcomes in terms of survival are better in pediatric patients. The mainstay of treatment is surgical excision with negative margins. This article reviews current concepts in demographics, etiology, management, and outcomes of malignant salivary tumors in children. PMID:26614703

  9. EphA2 Is a Potential Player of Malignant Cellular Behavior in Non-Metastatic Renal Cell Carcinoma Cells but Not in Metastatic Renal Cell Carcinoma Cells

    PubMed Central

    Cho, Min Chul; Cho, Sung Yong; Yoon, Cheol Yong; Lee, Seung Bae; Kwak, Cheol; Kim, Hyeon Hoe; Jeong, Hyeon

    2015-01-01

    Objectives To investigate the role of EphA2 in malignant cellular behavior in renal cell carcinoma (RCC) cells and whether FAK/RhoA signaling can act as downstream effectors of EphA2 on RCC cells. Methods Expression of EphA2 protein in non-metastatic RCC (Caki-2 and A498), metastatic RCC cells (Caki-1 and ACHN), HEK-293 cells and prostate cancer cells (PC-3 and DU-145; positive controls of EphA2 expression) was evaluated by Western blot. Changes in mRNA or protein expression of EphA2, FAK or membrane-bound RhoA following EphA2, FAK or RhoA small interfering RNA (siRNA) transfection were determined by reverse transcription polymerase chain reaction or Western blot. The effect of siRNA treatment on cellular viability, apoptosis and invasion was analyzed by cell counting kit-8, Annexin-V and modified Matrigel-Boyden assays, respectively. Results In all RCC cell lines, the expression of EphA2 protein was detectable at variable levels; however, in HEK-293 cells, EphA2 expression was very low. Treatment with EphA2 siRNA significantly reduced the expression of EphA2 mRNA and protein in all RCC cell lines. For non-metastatic RCC cells (Caki-2 and A498) but not metastatic RCC cells (Caki-1 and ACHN), cellular viability, invasiveness, resistance to apoptosis, expression of membrane-bound RhoA protein and FAK phosphorylation were significantly decreased in EphA2 siRNA-treated cells compared to the control. In non-metastatic RCC cells, FAK siRNA significantly attenuated the invasiveness, resistance to apoptosis, as well as expression of membrane-bound RhoA protein without changing protein expression of EphA2. RhoA siRNA significantly decreased the malignant cellular behavior and expression of membrane-bound RhoA protein without changing EphA2 protein expression or FAK phosphorylation. Conclusions Our data provide the first functional evidence that the EphA2/FAK/RhoA signaling pathway plays a critical role in the malignant cellular behavior of RCC and appears to be functional particularly in the early stage of malignant progression of non-metastatic RCC. PMID:26177500

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

    PubMed Central

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

    2013-01-01

    Celiac disease is characterized by intestinal inflammation caused by gluten, proteins which are widely contained in the Western diet. Mammalian digestive enzymes are only partly capable of cleaving gluten, and fragments remain that induce toxic responses in celiac patients. We found that the oral microbiome is a novel and rich source of gluten degrading enzymes. Here we report on the isolation and characterization of the cultivable resident oral microbes that are capable of cleaving gluten, with special emphasis on its immunogenic domains. Bacteria were obtained by a selective culturing approach and enzyme activities were characterised by: 1) Hydrolysis of paranitroanilide-derivatised gliadin-derived tripeptide substrates; 2) Gliadin degradation in-gel (gliadin zymography); 3) Gliadin degradation in solution; 4) Proteolysis of the highly immunogenic ?-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

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

    PubMed

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

    2013-09-01

    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

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

    PubMed

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

    2014-05-01

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

  13. Effects of near-infrared laser radiation on the survival and inflammatory potential of Candida spp. involved in the pathogenesis of chemotherapy-induced oral mucositis.

    PubMed

    Clemente, A M; Rizzetto, L; Castronovo, G; Perissi, E; Tanturli, M; Cozzolino, F; Cavalieri, D; Fusi, F; Cialdai, F; Vignali, L; Torcia, M G; Monici, M

    2015-10-01

    Candida spp. usually colonize ulcerative lesions of atrophic mucosa in patients with chemotherapy-induced oral mucositis inducing severe inflammation. The spread of antifungal-resistant strains strongly encouraged the search of complementary or alternative therapeutic strategies to cure inflamed mucosa. In this paper, we studied the effects of a near-infrared (NIR) laser system with dual-wavelength emission (808 nm + 904 nm) on the survival and inflammatory potential of C. albicans, C. glabrata, and C. parapsilosis. Laser treatment was performed with a Multiwave Locked System laser. Survival and apoptosis of fungal strains were evaluated by colony-forming units (CFU) counting and annexin V staining. Cytokine production was evaluated by ImmunoPlex array. Laser treatment significantly affected the survival of Candida spp. by inducing apoptosis and induced a lower production of inflammatory cytokines by dendritic cells compared to untreated fungi. No differences in the survival and inflammatory potential were recorded in treated or untreated Saccharomyces cerevisiae cells, used as the control non-pathogenic microorganism. Laser treatment altered the survival and inflammatory potential of pathogenic Candida spp. These data provide experimental support to the use of NIR laser radiation as a co-adjuvant of antifungal therapy in patients with oral mucositis (OM) complicated by Candida infections. PMID:26173694

  14. Brain-Penetrant, Orally Bioavailable Microtubule-Stabilizing Small Molecules Are Potential Candidate Therapeutics for Alzheimer’s Disease and Related Tauopathies

    PubMed Central

    2015-01-01

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

  15. Bioimpedance Detection of Oral Lichen Planus Used as Preneoplastic Model

    PubMed Central

    Tatullo, Marco; Marrelli, Massimo; Amantea, Massimiliano; Paduano, Francesco; Santacroce, Luigi; Gentile, Stefano; Scacco, Salvatore

    2015-01-01

    Introduction: Bioimpedance is a measure of the electrical properties of biological tissues. In the last two decades bioimpedance has been successfully introduced in clinical diagnosis of cancer. It has been demonstrated that tumoral tissues often show lower bioimpedance values than healthy tissues. The aim of this work is to assess the bioimpedentiometric differences between healthy and Oral Lichen Planus (OLP) affected oral mucosa, taking attention to the erosive form which may represent a potential pre-cancerous condition. Methods: 52 patients affected by OLP were recruited for bioimpedance examination of oral mucosa. Four electrical properties, resistance (R), reactance (Xc), phase angle (θ) and impedance (Z) of the tongue and of the intraoral mucosa, were measured. Results: We observed a significant increase of Z and a significant decrease of θ values in correspondence of OLP lesions compared to healthy oral mucosa, and a marked decrease of Z values in correspondence of erosive OLP lesions. Conclusions: These results provide evidence of the usefulness of bioimpedance assay for the characterization of healthy and clinically OLP affected mucosa. Bioimpedance is a valid aid in the early detection and clinical monitoring of the suspicious lesions which could lead to a potentially malignant evolution. The present research article is a valuable addition to the scientific literature of cancer prevention, and our findings can be considered extremely encouraging as they represent the initial step for a more wide clinical study for better define the different cut-off values in the different precancerous conditions occurring in the oral mucosa. PMID:26366210

  16. Dental status, dental rehabilitation procedures, demographic and oncological data as potential risk factors for infected osteoradionecrosis of the lower jaw after radiotherapy for oral neoplasms: a retrospective evaluation

    PubMed Central

    2013-01-01

    Purpose Retrospective evaluation of the dental status of patients with oral cancer before radiotherapy, the extent of dental rehabilitation procedures, demographic and radiotherapy data as potential risk factors for development of infected osteoradionecrosis of the lower jaw. Methods A total of 90 patients who had undergone radiotherapy for oral cancer were included into this retrospective evaluation. None of them had distant metastases. After tumour surgery the patients were referred to an oral and maxillofacial surgeon for dental examination and the necessary dental rehabilitation procedures inclusive potential tooth extraction combined with primary soft tissue closure. Adjuvant radiotherapy was started after complete healing of the gingiva (> 7 days after potential extraction). The majority of patients (n?=?74) was treated with conventionally fractionated radiotherapy with total doses ranging from 50-70Gy whereas further 16 patients received hyperfractionated radiotherapy up to 72Gy. The records of the clinical data were reviewed. Furthermore, questionnaires were mailed to the patients’ general practitioners and dentists in order to get more data concerning tumour status and osteoradionecrosis during follow-up. Results The patients’ dental status before radiotherapy was generally poor. On average 10 teeth were present, six of them were regarded to remain conservable. Extensive dental rehabilitation procedures included a mean of 3.7 tooth extractions. Chronic periodontitis with severe attachment loss was found in 40%, dental biofilm in 56%. An infected osteoradionecrosis (IORN) grade II according to (Schwartz et al., Am J Clin Oncol 25:168-171, 2002) was diagnosed in 11 of the 90 patients (12%), mostly within the first 4 years after radiotherapy. We could not find significant prognostic factors for the occurrence of IORN, but a trendwise correlation with impaired dental status, rehabilitation procedures, fraction size and tumour outcome. Conclusion The 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

  17. Anogenital malignancies and pre-malignancies.

    PubMed

    Henquet, C J M

    2011-08-01

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

  18. Oral lichen planus: An overview

    PubMed Central

    Krupaa, R. Jayasri; Sankari, S. Leena; Masthan, K. M. K.; Rajesh, E.

    2015-01-01

    Lichen planus is an immunologically mediated mucocutaneous disease that is triggered by varied etiological agents. The oral lichenoid reaction is considered a variant of the disease that needs to be clearly diagnosed as a separate entity from oral lichen planus and treated. They follow a strict cause-effector relationship, protocols that suggest the differentiation. Lichen planus has varied clinical forms in the oral mucosa and cutaneously that has different prognosis. This condition also arises in association with various other systemic conditions such as hypertension, diabetes mellitus. There have been cases reported in the esophagus, larynx, scalp, nail, cutaneous areas, especially arms and wrists, trunk. There is reported malignant transformation that essentiates careful examination, treatment protocol and regular follow-up sessions. This article throws light on the disease condition of oral lichen planus and oral lichenoid reaction that is essential for the differentiation and treatment. PMID:26015696

  19. Molecular and behavioral pharmacology of two novel orally-active 5HT2 modulators: potential utility as antipsychotic medications

    PubMed Central

    Morgan, Drake; Kondabolu, Krishnakanth; Kuipers, Allison; Sakhuja, Rajeev; Robertson, Kimberly L.; Rowland, Neil E.; Booth, Raymond G.

    2013-01-01

    Background Desired serotonin 5HT2 receptor pharmacology for treatment of psychoses is 5HT2A antagonism and/or 5HT2C agonism. No selective 5HT2A antagonist has been approved for psychosis and the only approved 5HT2C agonist (for obesity) also activates 5HT2A and 5HT2B receptors, which can lead to clinical complications. Studies herein tested the hypothesis that a dual-function 5HT2A antagonist/5HT2C agonist that does not activate 5HT2B receptors would be suitable for development as an antipsychotic drug, without liability for weight gain. Methods The novel compounds (+)- and (?)-trans-4-(4?-chlorophenyl)-N,N-dimethyl-2-aminotetralin (p-Cl-PAT) were synthesized, characterized in vitro for affinity and functional activity at human 5HT2 receptors, and administered by intraperitoneal (i.p.) and oral (gavage) routes to mice in behavioral paradigms that assessed antipsychotic efficacy and effects on feeding behavior. Results (+)- and (?)-p-Cl-PAT activated 5HT2C receptors, with (+)-p-Cl-PAT being 12-times more potent, consistent with its higher affinity across 5HT2 receptors. Neither p-Cl-PAT enantiomer activated 5HT2A or 5HT2B receptors at concentrations up to 300-times greater than their respective affinity (Ki), and (+)-p-Cl-PAT was shown to be a 5HT2A competitive antagonist. When administered i.p. or orally, (+)- and (?)-p-Cl-PAT attenuated the head-twitch response (HTR) in mice elicited by the 5HT2 agonist (?)-2,5-dimethoxy-4-iodoamphetamine (DOI) and reduced intake of a highly palatable food in non-food-deprived mice, with (+)-p-Cl-PAT being more potent across behavioral assays. Conclusions The novel in vitro pharmacology of (+)-p-Cl-PAT (5HT2A antagonism/5HT2C agonism without activation of 5HT2B) translated in vivo to an orally-active drug candidate with preclinical efficacy to treat psychoses without liability for weight gain. PMID:23665356

  20. Understanding Carcinogenesis for Fighting Oral Cancer

    PubMed Central

    Tanaka, Takuji; Ishigamori, Rikako

    2011-01-01

    Oral cancer is one of the major global threats to public health. Oral cancer development is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are able to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will give us important advances for detecting high-risk patients, monitoring preventive interventions, assessing cancer risk, and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from research using appropriate animal carcinogenesis models. New approaches, such as interventions with molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy. PMID:21772845

  1. The role of estrogen receptor {beta} (ER{beta}) in malignant diseases-A new potential target for antiproliferative drugs in prevention and treatment of cancer

    SciTech Connect

    Warner, Margaret; Center for Nuclear Receptors and Cell Signaling, Department of Biochemistry and Cell Biology, University of Houston, Houston, TX ; Gustafsson, Jan-Ake; Center for Nuclear Receptors and Cell Signaling, Department of Biochemistry and Cell Biology, University of Houston, Houston, TX

    2010-05-21

    The discovery of ER{beta} in the middle of the 1990s represents a paradigm shift in our understanding of estrogen signaling. It has turned out that estrogen action is not mediated by one receptor, ER{alpha}, but by two balancing factors, ER{alpha} and ER{beta}, which are often antagonistic to one another. Excitingly, ER{beta} has been shown to be widespread in the body and to be involved in a multitude of physiological and pathophysiological events. This has led to a strong interest of the pharmaceutical industry to target ER{beta} by drugs against various diseases. In this review, focus is on the role of ER{beta} in malignant diseases where the anti proliferative activity of ER{beta} gives hope of new therapeutic approaches.

  2. Melanoma differentiation-associated gene-7/interleukin-24 as a potential prognostic biomarker and second primary malignancy indicator in head and neck squamous cell carcinoma patients.

    PubMed

    Wang, Lin; Feng, Zhien; Wu, Huanhuan; Zhang, Shuai; Pu, Yinfei; Bian, Huan; Wang, Yixiang; Guo, Chuanbin

    2014-11-01

    The significance of melanoma differentiation-associated gene-7/interleukin-24 (MDA-7/IL-24) expression in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study was designed to investigate and evaluate the clinical significance of MDA-7/IL-24 expression in HNSCC by detecting expression by immunostaining in 131 HNSCC specimens. The function of MDA-7/IL-24 was investigated by real-time polymerase chain reaction (PCR) and Western blot in Ad5.mda-7-infected HNSCC cell lines. Our results showed that MDA-7/IL-24 was mainly expressed in the cytoplasm of HNSCC cells. MDA-7/IL-24 high patients presented with a favorable postoperative prognosis compared with MDA-7/IL-24 low patients, and high expression of MDA-7/IL-24 was significantly correlated with a lower incidence of second primary malignancies (SPMs) in the head and neck regions. In vitro assays showed that high expression of MDA-7/IL-24 could upregulate the expression of the epithelial terminal differentiation markers cytokeratin (KRT) 1, KRT4, KRT13, phosphorylated endoplasmic reticulum stress protein (p)-EIF2a, and the apoptosis-related protein cleaved caspase-3. It also downregulated the epithelial proliferative markers KRT5, KRT14, Integrin ?4, and anti-apoptosis protein Bcl-2, which might be partially involved in the underlying mechanisms of Ad.mda-7-mediated HNSCC differentiation and apoptosis. Our results indicate that MDA-7/IL-24 can be a prognostic biomarker and an indicator of second primary malignancies (SPM) in HNSCC. PMID:25091574

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

    PubMed

    Allikmets, Kristina

    2007-01-01

    The importance of renin-angiotensin-aldosterone system (RAAS) in diseases such as hypertension, congestive heart failure and chronic renal failure has long ago been recognized. It has also been established that inhibition of RAAS, using inhibitors of the angiotensin-converting enzyme (ACE) or angiotensin II receptor blockers (ARB), is an effective way to intervene with the pathogenesis of these disorders. Renin inhibitors block the RAAS at the highest level, at its origin, and might thus offer a new exciting approach for pharmacotherapy of arterial hypertension. Aliskiren is the first in a new class of orally active, non-peptide, low molecular weight renin inhibitors, and so far the only renin inhibitor that has progressed to phase III clinical trials. This review summarizes the available data on the pharmacokinetic and pharmacodynamic properties of aliskiren and its clinical development for treatment of arterial hypertension. PMID:18200801

  4. Estimation of Pyruvic acid in serum and saliva among healthy and potentially malignant disorder subjects – a stepping stone for cancer screening?

    PubMed Central

    Bhat, Anithraj; Prasad, Kakarla; Trivedi, Dhiraj; Acharya, Swathi

    2015-01-01

    Background According to Warburg’s effect, the rate of glycolysis increases in cancerous cells. This will increase overall levels of pyruvic acid. The present on-going study was conducted to estimate the levels of pyruvic acid in saliva and serum in normal, oral PMD subjects. Material and Methods A total of 50 subjects in healthy, PMD of the oral cavity individuals were selected based on clinical and histological criteria. Collected saliva and serum samples were subjected to pyruvic acid level estimation using biochemical analysis. Results Of the 50 participants 25 (13: Males; 12: Females) & 25 (16: Males; 9: Females) were PMD group. Independent samples t test showed statistically significant difference in serum & salivary pyruvic acid level in between 2 groups (p < 0.001 respectively). Conclusions Estimation of pyruvic acid showed sequential increase in the level in PMD group compared to healthy. Hence the study results open new direction in cancer screening. Key words:Pyruvic acid, glycolysis, warburg’s effect. PMID:26535090

  5. Oral nicotinamide and actinic keratosis: a supplement success story.

    PubMed

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

    2015-01-01

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

  6. Collecting and Storing Malignant, Borderline Malignant Neoplasms, and Related Samples From Young Patients With Cancer

    ClinicalTrials.gov

    2015-11-12

    Acute Undifferentiated Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Acute Lymphoblastic Leukemia; Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies; Childhood Chronic Myelogenous Leukemia; Chronic Lymphocytic Leukemia; Hairy Cell Leukemia; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Neoplasm of Uncertain Malignant Potential; Prolymphocytic Leukemia; Secondary Acute Myeloid Leukemia; T-cell Large Granular Lymphocyte Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  7. 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

    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

    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

  8. [Oral ulcers].

    PubMed

    Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

    2005-10-29

    Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology. PMID:16277953

  9. Oral leukoplakia, the ongoing discussion on definition and terminology

    PubMed Central

    2015-01-01

    In the past decades several definitions of oral leukoplakia have been proposed, the last one, being authorized by the World Health Organization (WHO), dating from 2005. In the present treatise an adjustment of that definition and the 1978 WHO definition is suggested, being : “A predominantly white patch or plaque that cannot be characterized clinically or pathologically as any other disorder; oral leukoplakia carries an increased risk of cancer development either in or close to the area of the leukoplakia or elsewhere in the oral cavity or the head-and-neck region”. Furthermore, the use of strict diagnostic criteria is recommended for predominantly white lesions for which a causative factor has been identified, e.g. smokers’ lesion, frictional lesion and dental restoration associated lesion. A final diagnosis of such leukoplakic lesions can only be made in retrospect after successful elimination of the causative factor within a somewhat arbitrarily chosen period of 4-8 weeks. It seems questionable to exclude “frictional keratosis” and “alveolar ridge keratosis” from the category of leukoplakia as has been suggested in the literature. Finally, brief attention has been paid to some histopathological issues that may cause confusion in establishing a final diagnosis of leukoplakia. Key words:Oral leukoplakia, potentially malignant oral disorders, definition. PMID:26449439

  10. Rheumatic Diseases and Malignancies

    PubMed Central

    BOJINCA, Violeta; JANTA, Iustina

    2012-01-01

    ABSTRACT There are many studies which demonstrate a higher risk for malignancy in patients with rheumatic diseases. There have been a number of possible explanations for the differences in the risk of certain malignancies in patients with rheumatic disease, compared with general population, but a clear mechanism is difficult to identify. Rheumatoid syndromes may be associated with malignancy as paraneoplastic conditions, which can antedate the neoplasm diagnosis. On the other hand, autoimmune rheumatic diseases have a higher risk of malignancy by themselves or because of the immunosuppressant treatments. PMID:23482881

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

    PubMed

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

    2014-05-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

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

    PubMed

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

    2015-01-01

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

  14. Oral Cancer

    MedlinePLUS

    ... consistency to exercises for weak oral muscles to learning totally new ways to swallow. In many cases, improvement is evident within several months. What other organizations have information about oral cancer? This list is ...

  15. Oral and oropharyngeal cancer.

    PubMed

    Huber, Michaell A; Tantiwongkosi, Bundhit

    2014-11-01

    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

  16. Evaluation of the genotoxic potential and acute oral toxicity of standardized extract of Andrographis paniculata (KalmCold).

    PubMed

    Chandrasekaran, C V; Thiyagarajan, P; Sundarajan, K; Goudar, Krishna S; Deepak, M; Murali, B; Allan, J Joshua; Agarwal, Amit

    2009-08-01

    Andrographis paniculata is used in the traditional medicine for cold and influenza remedy. The main endeavor in this study was to assess the genotoxicity of the standardized extract of A. paniculata (KalmCold) through three different in vitro tests: Ames, chromosome aberration (CA), and micronucleus (MN). Ames test was performed at 5000 microg/ml, 1581 microg/ml, 500 microg/ml, 158 microg/ml, 50 microg/ml, 16 microg/ml, while the clastogenicity tests were performed at 80 microg/ml, 26.6 microg/ml, 8.8 microg/ml for short-term treatment without S9; 345 microg/ml, 115 microg/ml, 38.3 microg/ml for short-term treatment with S9; and 46 microg/ml, 15.3 microg/ml, 5.1 microg/ml for long-term without S9 using DMSO as a vehicle control. Results of Ames test confirmed that KalmCold did not induce mutations both in the presence and absence of S9 in Salmonella typhimurium mutant strains TA98 and TAMix. In CA and MN, KalmCold did not induce clastogenicity in CHO-K1 cells in vitro. Based on our results, it is evident that KalmCold is genotoxically safe. Additionally in acute oral toxicity study, female rats were treated at 5000 mg/kg of KalmCold and observed for signs of toxicity for 14 days. KalmCold did not produce any treatment-related toxic effects in rats. PMID:19447157

  17. Hydroxypropyl-?-cyclodextrin functionalized calcium carbonate microparticles as a potential carrier for enhancing oral delivery of water-insoluble drugs.

    PubMed

    Zhang, Lihua; Zhu, Wufu; Lin, Qisi; Han, Jin; Jiang, Liqun; Zhang, Yanzhuo

    2015-01-01

    The objective of the present study was to demonstrate that a novel hydroxypropyl-?-cyclodextrin functionalized calcium carbonate (HP-?-CD/CC) based amorphous solid dispersion (ASD) can be used to increase the solubility and oral bioavailability of water-insoluble drugs. Irbesartan (IRB) was selected as a model compound and loaded into the nanoporous HP-?-CD/CC matrix using an immersion method. The IRB-loaded HP-?-CD/CC formulation was characterized by various analytical techniques, such as specific surface area analysis, scanning electron microscopy (SEM), dynamic light scattering (DLS), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Analyses with PXRD and DSC confirmed that IRB was fully converted into the amorphous form in the nanopores of HP-?-CD/CC. From the solubility and dissolution tests, it was observed that the aqueous solubility and dissolution rate of IRB-loaded HP-?-CD/CC were increased significantly compared with those of pure IRB and IRB-loaded mesoporous silica. Likewise, the IRB-loaded HP-?-CD/CC formulation exhibited better absorption compared with that of the commercially available IRB capsules in beagle dogs. The mean peak plasma concentration (C max) and the area under the mean plasma concentration-time curve (AUC[0?48]) of IRB-loaded HP-?-CD/CC were 1.56- and 1.52-fold higher than that of the commercial product, respectively. Furthermore, the IRB-loaded HP-?-CD/CC formulation exhibited excellent stability against re-crystallization. These results clearly demonstrate that HP-?-CD/CC based porous ASD is a promising formulation approach to improve the aqueous solubility and the in vivo absorption performance of a water-insoluble compound like IRB. PMID:25995635

  18. Genome-wide DNA methylation profiles in both precancerous conditions and clear cell renal cell carcinomas are correlated with malignant potential and patient outcome

    PubMed Central

    Arai, Eri; Ushijima, Saori; Fujimoto, Hiroyuki; Hosoda, Fumie; Shibata, Tatsuhiro; Kondo, Tadashi; Yokoi, Sana; Imoto, Issei; Inazawa, Johji; Hirohashi, Setsuo; Kanai, Yae

    2009-01-01

    To clarify genome-wide DNA methylation profiles during multistage renal carcinogenesis, bacterial artificial chromosome array-based methylated CpG island amplification (BAMCA) was performed. Non-cancerous renal cortex tissue obtained from patients with clear cell renal cell carcinomas (RCCs) (N) was at the precancerous stage where DNA hypomethylation and DNA hypermethylation on multiple bacterial artificial chromosome (BAC) clones were observed. By unsupervised hierarchical clustering analysis based on BAMCA data for their N, 51 patients with clear cell RCCs were clustered into two subclasses, Clusters AN (n = 46) and BN (n?=?5). Clinicopathologically aggressive clear cell RCCs were accumulated in Cluster BN, and the overall survival rate of patients in Cluster BN was significantly lower than that of patients in Cluster AN. By unsupervised hierarchical clustering analysis based on BAMCA data for their RCCs, 51 patients were clustered into two subclasses, Clusters AT (n?=?43) and BT (n?=?8). Clinicopathologically aggressive clear cell RCCs were accumulated in Cluster BT, and the overall survival rate of patients in Cluster BT was significantly lower than that of patients in Cluster AT. Multivariate analysis revealed that belonging to Cluster BT was an independent predictor of recurrence. Cluster BN was completely included in Cluster BT, and the majority of the BAC clones that significantly discriminated Cluster BN from Cluster AN also discriminated Cluster BT from Cluster AT. In individual patients, DNA methylation status in N was basically inherited by the corresponding clear cell RCC. DNA methylation alterations in the precancerous stage may generate more malignant clear cell RCCs and determine patient outcome. PMID:19037089

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

    PubMed

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

    2015-03-01

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

  20. Chemoprevention of oral cancer: Green tea experience

    PubMed Central

    Ramshankar, Vijayalakshmi; Krishnamurthy, Arvind

    2014-01-01

    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

  1. In vivo imaging polarimeter for oral precancer detection

    NASA Astrophysics Data System (ADS)

    Chung, Jungrae; Jung, Woonggyu; Wilder-Smith, Petra; Chen, Zhongping

    2005-04-01

    The Mueller matrix describes all the polarizing properties of a sample, and therefore the optical differences between non-cancerous and pre-cancerous tissue should be present within the matrix elements. We present in this paper that a high speedpolarimetry system generates 16 full Mueller matrices to characterize tissues. Feature extraction is done on the Mueller matrix elements resulting in the depolarizance and retardance images by polar decomposition to detect and classify of early oral cancers and pre-cancerous changes in epithelium, such as dysplasia. These images are compared with orthogonal polarization image and analyzed in an attempt to determine the important factors for the identification of cancerous lesions from their benign counterparts. Our results indicate that polarimetry has potential as a method for the in vivo early detection and diagnosis of oral premalignancy and malignancy.

  2. Epigenome and DNA methylation in oral squamous cell carcinoma.

    PubMed

    García, Mario Pérez-Sayáns; García-García, Abel

    2012-01-01

    Epigenetics studies and defines inherited changes in gene expression that are not encoded in the DNA sequence. The most studied epigenetic change in mammalian DNA is cytosine methylation in CpG dinucleotide areas. The other main group in epigenetic changes includes the posttranslational modifications of histones, mainly phosphorylation, deacetylation changes, and in the ubiquitinylation status. Oral squamous cell carcinoma is the most common malignancy of the oral cavity, and epigenetic changes are very common, as described in this chapter. Alterations in the DNA methylation status resulting from exposure to environmental stress agents have been documented even before birth. Although many epigenetic markers are potentially reversible, the mechanism still remains unclear and many epigenetic changes persist across cell lines and the life of the organism. PMID:22359295

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

    PubMed

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

    2013-09-01

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

  4. Lethal effect of blue light-activated hydrogen peroxide, curcumin and erythrosine as potential oral photosensitizers on the viability of Porphyromonas gingivalis and Fusobacterium nucleatum

    PubMed Central

    Habiboallh, Ghanbari; Mahbobeh, Naderi Nasab; Mina, Zareian Jahromi; Majid, Zakeri; Nooshin, Arjmand

    2015-01-01

    Objectives: Recently, photodynamic therapy (PDT) has been introduced as a new modality in oral bacterial decontamination. Current research aims to evaluate the effect of photodynamic killing of visible blue light in the presence of hydrogen peroxide, curcumin and erythrosine as potential oral photosensitizers on Porphyromonas gingivalis associated with periodontal bone loss and Fusobacterium nucleatum associated with soft tissue inflammation. Materials and methods: Standard suspension of P. gingivalis and F. nucleatum were exposed to Light Emitting Diode (LED) (440–480 nm) in combination with erythrosine (22 µm), curcumin (60 µM) and hydrogen peroxide (0.3 mM) for 5 min. Bacterial samples from each treatment groups (radiation-only group, photosensitizer-only group and blue light-activated photosensitizer group) were subcultured onto the surface of agar plates. Survival of these bacteria was determined by counting the number of colony forming units (CFU) after incubation. Results: Results for antibacterial assays on P. gingivalis confirmed that curcumin, Hydrogen peroxide and erythrosine alone exerted a moderate bactericidal effect which enhanced noticeably in conjugation with visible light. The survival rate of P. gingivalis reached zero present when the suspension exposed to blue light-activated curcumin and hydrogen peroxide for 2 min. Besides, curcumin exerted a remarkable antibacterial activity against F. nucleatum in comparison with erythrosine and hydrogen peroxide (P=0.00). Furthermore, the bactericidal effect of visible light alone on P. gingivalis as black-pigmented bacteria was significant. Conclusion: Our result suggested that visible blue light in the presence of erythrosine, curcumin and hydrogen peroxide would be consider as a potential approach of PDT to kill the main gramnegative periodontal pathogens. From a clinical standpoint, this regimen could be established as an additional minimally invasive antibacterial treatment of plaque induced periodontal pathologies. PMID:26246690

  5. The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery.

    PubMed

    Ma, Yiming; Fuchs, Adrian V; Boase, Nathan R B; Rolfe, Barbara E; Coombes, Allan G A; Thurecht, Kristofer J

    2015-08-01

    Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan-hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8h to 24h post-administration compared to the free NPs, due to a NP 'guarding' effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems. PMID:26117186

  6. Cancer associated fibroblasts in hematological malignancies

    PubMed Central

    Raffaghello, Lizzia; Vacca, Angelo; Pistoia, Vito; Ribatti, Domenico

    2015-01-01

    Tumor microenvironment plays an important role in cancer initiation and progression. In hematological malignancies, the bone marrow represents the paradigmatic anatomical site in which tumor microenvironment expresses its morphofunctional features. Among the cells participating in the composition of this microenvironment, cancer associated fibrobasts (CAFs) have received less attention in hematopoietic tumors compared to solid cancers. In this review article, we discuss the involvement of CAFs in progression of hematological malignancies and the potential targeting of CAFs in a therapeutic perspective. PMID:25474039

  7. Exostoses as a long-term sequela after pediatric hematopoietic progenitor cell transplantation: potential causes and increase risk of secondary malignancies from Ann & Robert H. Lurie Children's Hospital of Chicago.

    PubMed

    Danner-Koptik, Karina; Kletzel, Morris; Dilley, Kimberley J

    2013-08-01

    Allogeneic hematopoietic progenitor cell transplantation (HPCT) is a curative therapy for pediatric patients with both malignant and nonmalignant diseases. Single or multiple benign exostoses or osteochondromas have been reported after total body irradiation (TBI), as well as after focal irradiation. Patients exposed to TBI at a young age are at highest risk of developing exostoses. The objective of this institutional review board-approved study was to look at potential factors, besides radiation, that may play a role in development of exostoses. All patients who underwent allogeneic and autologous HPCT at a single institution between March 1992 and December 2003 and who developed an exostosis identified by clinical findings or as an incidental finding on a radiologic study were included. A case-control design matched patients with controls who had the same stem cell source. PMID:23721826

  8. Oral administration of aqueous extract of Carthami Flos induces macrophage activation and preferentially potentiates type 1 helper T-cell response in vivo.

    PubMed

    Choi, Youn-Hwa; Do, Jeong-Su; Seo, Hyo-Jung; Hwang, Jin-Ki; Kim, Jun-Hee; Song, Eun-Jung; Nam, Sang-Yun

    2007-01-01

    In vivo immunomodulatory activity of aqueous extract of Carthami Flos (AECF) was investigated using a mouse model immunized with keyhole limpet hemocyanin. Serum level of Ag-specific IgG2a was significantly elevated by oral administration of AECF but not IgG1. However, no selective B-cell proliferation by AECF was observed in vivo. Ag-specific proliferation and IFN-gamma and IL-5 production of draining lymph node T cells also was higher in AECF-treated mice when compared with water-treated control mice. However, AECF failed to enhance nonspecific T-cell response under CD3 stimulation. These results led us to hypothesize that AECF potentiates Ag-specific T-cell response, possibly through activation of antigen presenting cells (APC) other than B cells. Functional assessment of splenic macrophages showed that AECF administration significantly enhances IL-12 production as well as APC activity for IFN-gamma production and STAT-4 activation by T cells. Collectively, these data strongly support that AECF preferentially potentiates immune response polarized toward TH1 and for which increased activation of macrophages is most likely to be responsible. The present data implicate a possible application of AECF to potentiate cellular immunity and, we hope, prevent intracellular infections. PMID:17849267

  9. Discrimination of premalignant conditions of oral cancer using Raman spectroscopy of urinary metabolites

    NASA Astrophysics Data System (ADS)

    Elumalai, Brindha; Rajasekaran, Ramu; Aruna, Prakasarao; Koteeswaran, Dornadula; Ganesan, Singaravelu

    2015-03-01

    Oral cancers are considered to be one of the most commonly occurring malignancy worldwide. Over 70% of the cases report to the doctor only in advanced stages of the disease, resulting in poor survival rates. Hence it is necessary to detect the disease at the earliest which may increase the five year survival rate up to 90%. Among various optical spectroscopic techniques, Raman spectroscopy has been emerged as a tool in identifying several diseased conditions, including oral cancers. Around 30 - 80% of the malignancies of the oral cavity arise from premalignant lesions. Hence, understanding the molecular/spectral differences at the premalignant stage may help in identifying the cancer at the earliest and increase patient's survival rate. Among various bio-fluids such as blood, urine and saliva, urine is considered as one of the diagnostically potential bio-fluids, as it has many metabolites. The distribution and the physiochemical properties of the urinary metabolites may vary due to the changes associated with the pathologic conditions. The present study is aimed to characterize the urine of 70 healthy subjects and 51 pre-malignant patients using Raman spectroscopy under 785nm excitation, to know the molecular/spectral differences between healthy subjects and premalignant conditions of oral malignancy. Principal component analysis based Linear discriminant analysis were also made to find the statistical significance and the present technique yields the sensitivity and specificity of 86.3% and 92.9% with an overall accuracy of 90.9% in the discrimination of premalignant conditions from healthy subjects urine.

  10. Childhood ovarian malignancy.

    PubMed

    Mahadik, Kalpana; Ghorpade, Kanchanmala

    2014-04-01

    Objective of this article is to appraise diagnostic aspects and treatment modalities in childhood ovarian tumor in background of available evidence. Literature search on Pubmed revealed various aspects of epidemiology, histopathological diagnosis, and treatment of pediatric ovarian tumor. 85 % of childhood tumors are germ cell tumors. The varied histopathological picture in germ cell tumors poses a diagnostic and therapeutic challenge. Immunohistochemistry and newer genetic markers like SALL4 and karyopherin-2 (KPNA2) have been helpful in differentiating ovarian yolk sac tumor from dysgerminoma, teratomas, and other pictures of hepatoid, endometrioid, clear cell carcinomatous, and adenocarcinomatous tissues with varied malignant potential. Before platinum therapy, these tumors were almost fatal in children. Fertility-conserving surgery with bleomycin, etoposide, and cisplatin has dramatically changed the survival rates in these patients. This modality gives cancer cure with healthy offspring to female patients with childhood ovarian tumor. Evidence also supports this protocol resulting in successful pregnancy rates and safety of cytotoxic drugs in children born to these patients. PMID:24757335

  11. Malignant liver tumors.

    PubMed

    Honeyman, Joshua N; La Quaglia, Michael P

    2012-08-01

    Malignant tumors of the liver comprise a relatively small fraction of the total number of pediatric malignancies. However, these tumors can be a significant cause of morbidity and mortality, and there have been significant therapeutic gains during the past few decades through advances in systemic therapy and surgical treatment. Even in patients with advanced local disease, complete resection is now a possibility because of improvements in liver transplantation techniques. In this review, we will discuss the staging and treatment of common malignant tumors of the liver. PMID:22800977

  12. Malignant melanoma maxilla

    PubMed Central

    Devi, Seema; Sinha, Richi; Singh, Rakesh Kumar

    2015-01-01

    A malignant melanoma is a highly lethal melanocytic neoplasm. A neoplasm usually affects the skin. Malignant melanomas in the head and neck region are rare, accounting for less than 1% of all melanomas. Malignant melanoma of the nose and paranasal sinuses is an aggressive disease typically presenting at an advanced stage, with a 5-year survival rate ranging 20-30%. Melanomas are tumors arising from melanocytes, which are neuroectodermally derived cells located in the basal layers of the skin. This is a case report of a 35-year-old male, who presented with very aggressive disease and developed liver metastasis.

  13. Oral treatments of Echinococcus multilocularis-infected mice with the antimalarial drug mefloquine that potentially interacts with parasite ferritin and cystatin.

    PubMed

    Küster, Tatiana; Stadelmann, Britta; Rufener, Reto; Risch, Corina; Müller, Joachim; Hemphill, Andrew

    2015-11-01

    This study investigated the effects of oral treatments of Echinococcus multilocularis-infected mice with the antimalarial drug mefloquine (MEF) and identified proteins that bind to MEF in parasite extracts and human cells by affinity chromatography. In a pilot experiment, MEF treatment was applied 5 days per week and was intensified by increasing the dosage stepwise from 12.5 mg/kg to 200 mg/kg during 4 weeks followed by treatments of 100 mg/kg during the last 7 weeks. This resulted in a highly significant reduction of parasite weight in MEF-treated mice compared with mock-treated mice, but the reduction was significantly less efficacious compared with the standard treatment regimen of albendazole (ABZ). In a second experiment, MEF was applied orally in three different treatment groups at dosages of 25, 50 or 100 mg/kg, but only twice a week, for a period of 12 weeks. Treatment at 100 mg/kg had a profound impact on the parasite, similar to ABZ treatment at 200 mg/kg/day (5 days/week for 12 weeks). No adverse side effects were noted. To identify proteins in E. multilocularis metacestodes that physically interact with MEF, affinity chromatography of metacestode extracts was performed on MEF coupled to epoxy-activated Sepharose(®), followed by SDS-PAGE and in-gel digestion LC-MS/MS. This resulted in the identification of E. multilocularis ferritin and cystatin as MEF-binding proteins. In contrast, when human cells were exposed to MEF affinity chromatography, nicotinamide phosphoribosyltransferase was identified as a MEF-binding protein. This indicates that MEF could potentially interact with different proteins in parasites and human cells. PMID:26395219

  14. Metastatic Tumours to the Oral Cavity: Report of Three Cases

    PubMed Central

    Astreidis, Ioannis T.; Kontos, Konstantinos I.; Lazaridou, Maria N.; Bourlidou, Eleni T.; Gerasimidou, Domniki K.; Vladika, Natalia P.; Mangoudi, Doxa L.

    2015-01-01

    ABSTRACT Background Metastatic tumours to the oral cavity from distant organs are uncommon and represent approximately 1 - 3% of all oral malignancies. Such metastases can occur to the bone or to the oral soft tissues. Almost any malignancy from any site is capable of metastasis to the oral cavity and a wide variety of tumours have been reported to spread to the mouth. Methods Careful examination of the oral cavity and a high degree of clinical suspicion as well as a multidisciplinary approach are suggested. Results In this article we present three patients, a female and two males with metastatic tumours to the oral cavity, who were referred to our Department. The primary tumours were invasive lobular breast carcinoma, gastric adenocarcinoma and small cell lung carcinoma respectively. Conclusions Metastases to the oral cavity are quite uncommon among population. They usually present with symptoms similar to odontogenic infections and benign tumours, causing a delayed diagnosis and treatment. PMID:26904182

  15. Malignant eroticized countertransference.

    PubMed

    Chessick, R D

    1997-01-01

    Gabbard (1994) divided the pathology of therapists, both male and female, who commit sexual boundary violations into those who are psychotic, those who are predatory psychopaths, those engaging in masochistic surrender, and those called "the lovesick therapist." Lovesick therapists are the most common type and manifest crucial narcissistic themes of "a desperate need for validation by their patients, a hunger to be loved and idealized, and a tendency to use patients to regulate their own self-esteem" (p. 127). Among the psychodynamic aspects of this curiously circumscribed area of loss of reality testing that makes it difficult for the therapist to see how self-destructive and harmful such enactment is, are an unconscious reenactment of incestuous longings, a misperception of the patient's wish for maternal nurturance as a sexual overture, enactments of rescue fantasies, a projected idealization of the self of the therapist, a confusion of the therapist's needs with the patient's needs, a fantasy that love is curative, acting out disavowed rage at the patient, or rage at an organization, an institute, or one's training analyst, a manic defense against mourning, a narcissistic fantasy that their sexual affair is an exception, insecurity regarding masculine identity, and assorted primitive preoedipal themes. Gabbard's (1991) erotized countertransference is one variety of what I have termed malignant eroticized countertransference. His variety is a development that occurs under the pressure of the patient's preemptive and compelling expressions of lust and love, the patient's erotic transference. But malignant eroticized countertransference can also occur without the patient having offered any such expressions; it can even occur on first meeting the patient when he or she walks into the office! This is akin to the romantic "love-at-first-sight" theme so favored in the movies and by novelists, but it is always pathological when it occurs in the therapeutic situation. Countertransference enactments are a creation between the patient and the therapist on a continuum from one pole, where the patient has just walked into the office and contributes almost nothing directly, to the other pole, where the therapist loses control of himself or herself as a response to the unbearable pressure of the patient's lust. In the treatment of malignant eroticized countertransference it seems clear from this discussion that every case should be evaluated psychodynamically and the treatment should be made to fit the patient, not the patient to the treatment. Each situation should be studied in psychodynamic depth without preconceptions based on generalizations or formulas. Therapists who are psychotic should of course be treated with antipsychotic drugs and usually should not be allowed to practice any further. Therapists who are psychopathic or sociopathic predators should certainly never be allowed to practice. Some of the individuals who are "lovesick," or, as I put it "love/lust obsessed," or those who have made a masochistic surrender to a sadistic destructive patient, are in need of reanalysis and have the potential to continue as effective therapists under careful supervision. Therapists like this do not deserve to be summarily dismissed from the profession but, like therapists who develop other serious neurotic problems, should receive appropriate help from us. PMID:9395991

  16. Nucleus Accumbens-Associated Protein 1 Expression Has Potential as a Marker for Distinguishing Oral Epithelial Dysplasia and Squamous Cell Carcinoma

    PubMed Central

    Sekine, Joji; Kanno, Takahiro; Nariai, Yoshiki; Urano, Takeshi

    2015-01-01

    Background Oral epithelial dysplasia (OED) and carcinoma in situ (CIS) are defined by dysplastic cells in the epithelium. Over a third of oral squamous cell carcinoma (OSCC) patients present with associated OED. However, accurate histopathological diagnosis of such lesions is difficult. Nucleus accumbens-associated protein 1 (NAC1) is a member of the Pox virus and Zinc finger/Bric-a-brac Tramtrack Broad complex family of proteins, and is overexpressed in OSCC. This study aimed to determine whether NAC1 has the potential to be used as a marker to distinguish OED and OSCC. Methods and Findings The study included 114 patients (64 men, 50 women). There were 67, 10, and 37 patients with OED, CIS, and OSCC, respectively. NAC1 labeling indices (LIs) and immunoreactivity intensities (IRI) were evaluated. The patients’ pathological classification was significantly associated with age, sex, NAC1 LIs, and NAC1 IRI (p = 0.025, p = 0.022, p < 0.001, and p < 0.001, respectively). As a result of multivariate analysis, a predictive model was made; this identified the NAC1 LIs (OR [95% CI] 1.18 [1.11–1.28], p < 0.001) and NAC1 IRI (0.78 [0.68–0.86], p < 0.001) as predictive factors for CIS/OSCC. The NAC1 LIs/IRI cut-off values which discriminated between OED and CIS/OSCC were 50%/124 pixels. For NAC1 LIs with > 50% positivity the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.766, 0.910, 0.857, and 0.847, respectively. For NAC1 IRI with ? 124 positive pixels, the sensitivity, specificity, PPV, and NPV were 0.787, 0.866, 0.804, and 0.853, respectively. Though there are several potential limitations to this study and the results were obtained from a retrospective analysis of a single site cohort, the data suggest that the NAC1 LIs/IRI is a strong predictor of CIS/OSCC. Conclusions NAC1 has potential as a marker for distinguishing OED from CIS/OSCC. PMID:26172271

  17. Salivary biomarkers for detection of oral squamous cell carcinoma – current state and recent advances

    PubMed Central

    Yakob, Maha; Fuentes, Laurel; Wang, Marilene B.; Abemayor, Elliot; Wong, David T.W.

    2014-01-01

    Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity. Detection of OSCC is currently based on thorough clinical oral examination combined with biopsy for histological analysis. Most cases of OSCC are not detected until the cancer has developed into advanced stages; thus, a reliable early stage diagnostic marker is needed. This literature review presents an overview of the status of current advances in salivary diagnostics for OSCC. Though many protein and mRNA salivary biomarkers have been identified that can detect OSCC with high sensitivity and specificity, the most discernable findings occur with the use of multiple markers. Studies that incorporate proteomic, transcriptomic, and potentially additional “omics”, including methylomics, need to be initiated to bring technology to clinical applications and allow the best use of saliva in diagnosing OSCC. PMID:24883261

  18. Prospective Study of Dental Intervention for Hematopoietic Malignancy

    PubMed Central

    Tsuji, K.; Akashi, M.; Furudoi, S.; Yakushijin, K.; Kawamoto, S.; Okamura, A.; Matsuoka, H.; Komori, T.

    2015-01-01

    Various chemotherapeutic agents used in patients with hematopoietic malignancy cause serious side effects, including myelosuppression and immunosuppression. Immunosuppression makes patients more susceptible to infection, resulting in an increased risk of infectious complications, including the development of severe septicemia that may be life-threatening. It is necessary for dental staff to be familiar with an appropriate protocol in such cases and to share information about the chemotherapy with a hematologist. To verify the effectiveness of our dental intervention protocol, we conducted a prospective study on the incidence of complications for each myelosuppressive grade of chemotherapy in patients with hematopoietic malignancy. We compared the incidence of complications between treatment P (patients who finished all the dental treatments according to the protocol) and treatment Q (patients who did not) per grade (A, B, C, D) and incidence of systemic or oral findings. We also compared the incidence of oral complication related to the residual teeth between first chemo (patients who were undergoing chemotherapy for the first time) and prior chemo (not the first time). There were significant differences in inflammatory complications between treatment P and treatment Q. We found that both systemic and oral inflammatory complications increased with higher-grade myelosuppressive chemotherapy. Additionally, there was a significant difference between the incidence of oral complications related to the residual teeth between first chemo and prior chemo. Complete implementation of the dental intervention protocol was associated with fewer oral and systemic infectious and inflammatory complications in patients with hematopoietic malignancies undergoing chemotherapy. The incidence of oral and systemic complications also increased with grade of chemotherapy. These results support the validity of our dental intervention protocol. We should pay close attention to the oral state of de novo hematopoietic malignancy patients. PMID:25503612

  19. Screening and analysis of the potential bioactive components in rabbit plasma after oral administration of hot-water extracts from leaves of Bambusa textilis McClure.

    PubMed

    Wang, Jin; Yue, Yong-De; Tang, Feng; Sun, Jia

    2012-01-01

    Bambusa textilis McClure is a traditional Chinese medicinal plant belonging to the Bambusoideae subfamily and used to treat chronic fever and infectious diseases. To investigate the bioactive compounds absorbed in the rabbit blood after oral administration of hot-water extracts from the leaves of B. textilis McClure, a validated chromatographic fingerprint method was established using LC-Q-TOF-MS. Twenty compounds in bamboo leaves and three potential bioactive compounds in rabbit plasma were detected. Of the twenty detected compounds in vitro, fifteen of which were tentatively identified either by comparing the retention time and mass spectrometry data with that of reference compounds or by reviewing the literature. Three potential bioactive compounds, including (E)-pcoumaric acid, (Z)-p-coumaric acid, and apigenin-8-C-?-D-(2"-O-?-L-rhamnosyl)-glucopyranoside, were detected in both the leaves of B. textilis McClure and rabbit plasma. Of the three compounds, apigenin-8-C-?-D-(2"-O-?-L-rhamnosyl)glu