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Sample records for potential oral markers

  1. 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

  2. Salivary markers of oxidative stress in oral diseases

    PubMed Central

    Tóthová, L'ubomíra; Kamodyová, Natália; Červenka, Tomáš; Celec, Peter

    2015-01-01

    Saliva is an interesting alternative diagnostic body fluid with several specific advantages over blood. These include non-invasive and easy collection and related possibility to do repeated sampling. One of the obstacles that hinders the wider use of saliva for diagnosis and monitoring of systemic diseases is its composition, which is affected by local oral status. However, this issue makes saliva very interesting for clinical biochemistry of oral diseases. Periodontitis, caries, oral precancerosis, and other local oral pathologies are associated with oxidative stress. Several markers of lipid peroxidation, protein oxidation and DNA damage induced by reactive oxygen species can be measured in saliva. Clinical studies have shown an association with oral pathologies at least for some of the established salivary markers of oxidative stress. This association is currently limited to the population level and none of the widely used markers can be applied for individual diagnostics. Oxidative stress seems to be of local oral origin, but it is currently unclear whether it is caused by an overproduction of reactive oxygen species due to inflammation or by the lack of antioxidants. Interventional studies, both, in experimental animals as well as humans indicate that antioxidant treatment could prevent or slow-down the progress of periodontitis. This makes the potential clinical use of salivary markers of oxidative stress even more attractive. This review summarizes basic information on the most commonly used salivary markers of oxidative damage, antioxidant status, and carbonyl stress and the studies analyzing these markers in patients with caries or periodontitis. PMID:26539412

  3. Galectin-7 as a potential predictive marker of chemo- and/or radio-therapy resistance in oral squamous cell carcinoma.

    PubMed

    Matsukawa, Sho; Morita, Kei-ichi; Negishi, Ayako; Harada, Hiroyuki; Nakajima, Yusuke; Shimamoto, Hiroaki; Tomioka, Hirofumi; Tanaka, Kae; Ono, Masaya; Yamada, Tesshi; Omura, Ken

    2014-04-01

    Treatment of advanced oral squamous cell carcinoma (OSCC) requires the integration of multimodal approaches. The aim of this study was to identify predictors of tumor sensitivity to preoperative radiotherapy/chemotherapy for OSCC in order to allow oncologists to determine optimum therapeutic strategies without the associated adverse effects. Here, the protein expression profiles of formalin-fixed paraffin-embedded (FFPE) tissue samples from 18 OSCC patients, termed learning cases, who received preoperative chemotherapy and/or radiotherapy followed by surgery were analyzed by quantitative proteomics and validated by immunohistochemistry in 68 test cases as well as in the 18 learning cases. We identified galectin-7 as a potential predictive marker of chemotherapy and/or radiotherapy resistance, and the sensitivity and specificity of the galectin-7 prediction score (G7PS) in predicting this resistance was of 96.0% and 39.5%, respectively, in the 68 test cases. The cumulative 5-year disease-specific survival rate was 75.2% in patients with resistant prediction using G7PS and 100% in patients with sensitive prediction. In vitro overexpression of galectin-7 significantly decreased cell viability in OSCC cell line. Therefore, our findings suggest that galectin-7 is a potential predictive marker of chemotherapy and/or radiotherapy resistance in patients with OSCC. PMID:24515895

  4. Galectin-7 as a potential predictive marker of chemo-and/or radio-therapy resistance in oral squamous cell carcinoma

    PubMed Central

    Matsukawa, Sho; Morita, Kei-ichi; Negishi, Ayako; Harada, Hiroyuki; Nakajima, Yusuke; Shimamoto, Hiroaki; Tomioka, Hirofumi; Tanaka, Kae; Ono, Masaya; Yamada, Tesshi; Omura, Ken

    2014-01-01

    Treatment of advanced oral squamous cell carcinoma (OSCC) requires the integration of multimodal approaches. The aim of this study was to identify predictors of tumor sensitivity to preoperative radiotherapy/chemotherapy for OSCC in order to allow oncologists to determine optimum therapeutic strategies without the associated adverse effects. Here, the protein expression profiles of formalin-fixed paraffin-embedded (FFPE) tissue samples from 18 OSCC patients, termed learning cases, who received preoperative chemotherapy and/or radiotherapy followed by surgery were analyzed by quantitative proteomics and validated by immunohistochemistry in 68 test cases as well as in the 18 learning cases. We identified galectin-7 as a potential predictive marker of chemotherapy and/or radiotherapy resistance, and the sensitivity and specificity of the galectin-7 prediction score (G7PS) in predicting this resistance was of 96.0% and 39.5%, respectively, in the 68 test cases. The cumulative 5-year disease-specific survival rate was 75.2% in patients with resistant prediction using G7PS and 100% in patients with sensitive prediction. In vitro overexpression of galectin-7 significantly decreased cell viability in OSCC cell line. Therefore, our findings suggest that galectin-7 is a potential predictive marker of chemotherapy and/or radiotherapy resistance in patients with OSCC. Identification of proteins differentially expressed in OSSC samples from patients sensitive or resistant. The samples were processed by LC-MS and analyzed with 2DICAL. PMID:24515895

  5. Molecular markers in oral lichen planus: A systematic review.

    PubMed

    Sagari, Shitalkumar; Sanadhya, Sudhanshu; Doddamani, Mallikarjun; Rajput, Rajan

    2016-01-01

    Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that is usually detected in 0.5-2.2% of the human population. Among these, only 0.5-2.9% of the lesions progress to carcinoma. However, there are no prognostic markers available presently to recognize the increased risk in malignant transformation of the lesions. Selected markers for cell proliferation, adhesion, apoptosis and lymphocytic infiltration were analyzed by immunohistochemistry in addition to static cytometry for DNA content. The concept linking OLP and oral squamous cell carcinoma states that chronic inflammation results in crucial DNA damage, which further progresses to development of carcinoma. Even though in the past decade, enormous information has been accumulated on malignant potential of OLP, its transformation still remains unclear. Hence, the purpose of this article was to review cellular and molecular markers to understand the pathogenesis of OLP and its progression toward malignancy. PMID:27194873

  6. Molecular markers in oral lichen planus: A systematic review

    PubMed Central

    Sagari, Shitalkumar; Sanadhya, Sudhanshu; Doddamani, Mallikarjun; Rajput, Rajan

    2016-01-01

    Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that is usually detected in 0.5–2.2% of the human population. Among these, only 0.5–2.9% of the lesions progress to carcinoma. However, there are no prognostic markers available presently to recognize the increased risk in malignant transformation of the lesions. Selected markers for cell proliferation, adhesion, apoptosis and lymphocytic infiltration were analyzed by immunohistochemistry in addition to static cytometry for DNA content. The concept linking OLP and oral squamous cell carcinoma states that chronic inflammation results in crucial DNA damage, which further progresses to development of carcinoma. Even though in the past decade, enormous information has been accumulated on malignant potential of OLP, its transformation still remains unclear. Hence, the purpose of this article was to review cellular and molecular markers to understand the pathogenesis of OLP and its progression toward malignancy. PMID:27194873

  7. 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-μm-thick sections of tissue were taken from paraffin-embedded wax blocks for immunohistochemical staining for EGFR. Results. All the control cases showed positive expression for EGFR, while 20% of oral leukoplakia and 40% of OSMF cases showed strong expression (3+), 40% of OL and 30% of OSMF cases showed weak expression (2+), and 40% of OLand 30% of OSMF cases showed poor expression (1+) compared to controls (P=0.012). Conclusion. EGFR expression levels in the premalignant lesion appear to be a sensitive factor in predicting the neoplastic potential. This suggests that EGFR may serve as a biological marker to identify high-risk subgroups and guide prophylactic therapy with chemopreventive drugs or surgical intervention to prevent progression to carcinoma. Hence, further investigations in the direction of chemopreventive trials with a larger sample size are suggested to determine its role in the head and neck tumorigenesis. PMID:26697149

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

    PubMed

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

    2015-01-01

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

  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

  10. Potential markers of preeclampsia – a review

    PubMed Central

    Grill, Simon; Rusterholz, Corinne; Zanetti-Dällenbach, Rosanna; Tercanli, Sevgi; Holzgreve, Wolfgang; Hahn, Sinuhe; Lapaire, Olav

    2009-01-01

    Preeclampsia is a leading cause of maternal and fetal/neonatal mortality and morbidity worldwide. The early identification of patients with an increased risk for preeclampsia is therefore one of the most important goals in obstetrics. The availability of highly sensitive and specific physiologic and biochemical markers would allow not only the detection of patients at risk but also permit a close surveillance, an exact diagnosis, timely intervention (e.g. lung maturation), as well as simplified recruitment for future studies looking at therapeutic medications and additional prospective markers. Today, several markers may offer the potential to be used, most likely in a combinatory analysis, as predictors or diagnostic tools. We present here the current knowledge on the biology of preeclampsia and review several biochemical markers which may be used to monitor preeclampsia in a future, that, we hope, is not to distant from today. PMID:19602262

  11. Potentially malignant oral lesions: clinicopathological correlations.

    PubMed

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

    2016-03-01

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

  12. Origin of Ameloblastoma From Basal Cells of the Oral Epithelium- Establishing the Relation Using Neuroectodermal Markers

    PubMed Central

    Suneela, S; Narayan, T V; Shreedhar, Balasundari; Mohanty, Leeky; Shenoy, Sadhana; Swaminathan, Uma

    2014-01-01

    Background and Objectives: Basal cell layer of the oral epithelium has been rightfully regarded as a potential source of odontogenic tumours and cysts, but, without substantial evidence. Also, whether the basal cell layer retains within it, some properties of ectomesenchyme, which was imbibed during the early embryogenesis and hence its neuroectodermal relation, is not known. Here, an attempt is made to establish the hidden neuroectodermal potential of the oral epithelium, especially the basal layer, by observing the expression of known neuroectodermal markers, NSE (Neuron Specific Enolase), Synaptophysin and CD99. The expression of the same markers has also been studied in Ameloblastoma, connecting it with oral epithelium, in turn establishing basal cell layer as a potential source of Ameloblastoma. Materials and Methods: Sections of formalin fixed, paraffin embedded tissue samples of 20 cases of Ameloblastoma and 10 cases of Normal Retromolar mucosa, were stained immunohistochemically with NSE, Synaptophysin, CD99 and also with CK-19 and evaluated for positive expression. Results: Positive reaction was obtained in all the cases of Ameloblastoma and NRM (Normal Retromolar mucosa) with NSE, all the cases of Ameloblastoma and eight cases of NRM with Synaptophysin and in six cases of Ameloblastoma and NRM with CD99. The staining was diffuse and more marked in case of NSE than Synaptophysin and CD99. CK19 staining done to assure that the tissue antigenicity was maintained was positive in all the samples. Interpretation and Conclusion: A strong relationship between the neuroectoderm, Ameloblastoma and the basal layer of the oral epithelium is established by the study. It favours the hypothesis that the basal cell layer of oral mucosa may be the sought out culprit in most cases of the Ameloblastomas, especially those occurring in the non-tooth bearing area. This would call for the need to incorporate additional therapy in the form of mucosal striping along with the

  13. Biochemical markers in oral submucous fibrosis: A review and update

    PubMed Central

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

    2013-01-01

    Oral submucous fibrosis (OSMF) is a potentially malignant oral condition effectively linked to the causative habit of chewing areca nut. Since its first description in the 1950s, numerous epidemiological, biochemical, histological, and genetic studies have been reported. While most studies point out to the cause and effect of areca nut, co-additive factors are also implicated in the progression and malignant transformation of this condition. Biochemical investigations have concentrated on outlining such changes in the blood, serum or tissues of these patients and have given insights on the possible pathogenesis of OSMF. This article attempts to compile details of biochemical investigations in OSMF and summarize and infer on the findings. PMID:24348612

  14. Leptin receptor expression and Gln223Arg polymorphism as prognostic markers in oral and oropharyngeal cancer.

    PubMed

    Rodrigues, P R S; Maia, L L; Santos, M; Peterle, G T; Alves, L U; Takamori, J T; Souza, R P; Barbosa, W M; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

    2015-01-01

    The leptin gene product is released into the blood stream, passes through the blood-brain barrier, and finds the leptin receptor (LEPR) in the central nervous system. This hormone regulates food intake, hematopoiesis, inflammation, immunity, differentiation, and cell proliferation. The LEPR Gln223Arg polymorphism has been reported to alter receptor function and expression, both of which have been related with prognostics in several tumor types. Furthermore, several studies have shown a relationship between the Gln223Arg polymorphism and tumor development, and its role in oral and oropharyngeal squamous cell carcinoma is now well understood. In this study, 315 DNA samples were used for LEPR Gln223Arg genotyping and 87 primary oral and oropharyngeal squamous cell carcinomas were used for immunohistochemical expression analysis, such that a relationship between these and tumor development and prognosis could be established. Homozygous LEPR Arg223 was found to be associated with a 2-fold reduction in oral and oropharyngeal cancer risk. In contrast, the presence of the Arg223 allele in tumors was associated with worse disease-free and disease-specific survival. Low LEPR expression was found to be an independent risk factor, increasing the risk for lymph node metastasis 4-fold. In conclusion, the Gln223Arg polymorphism and LEPR expression might be valuable markers for oral and oropharyngeal cancer, suggesting that LEPR might serve as a potential target for future therapies. PMID:26634459

  15. Keratins 17 and 19 expression as prognostic markers in oral squamous cell carcinoma.

    PubMed

    Coelho, B A; Peterle, G T; Santos, M; Agostini, L P; Maia, L L; Stur, E; Silva, C V M; Mendes, S O; Almança, C C J; Freitas, F V; Borçoi, A R; Archanjo, A B; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

    2015-01-01

    Five-year survival rates for oral squamous cell carcinoma (OSCC) are 30% and the mortality rate is 50%. Immunohistochemistry panels are used to evaluate proliferation, vascularization, apoptosis, HPV infection, and keratin expression, which are important markers of malignant progression. Keratins are a family of intermediate filaments predominantly expressed in epithelial cells and have an essential role in mechanical support and cytoskeleton formation, which is essential for the structural integrity and stability of the cell. In this study, we analyzed the expressions of keratins 17 and 19 (K17 and K19) by immunohistochemistry in tumoral and non-tumoral tissues from patients with OSCC. The results show that expression of these keratins is higher in tumor tissues compared to non-tumor tissues. Positive K17 expression correlates with lymph node metastasis and multivariate analysis confirmed this relationship, revealing a 6-fold increase in lymph node metastasis when K17 is expressed. We observed a correlation between K17 expression with disease-free survival and disease-specific death in patients who received surgery and radiotherapy. Multivariate analysis revealed that low expression of K17 was an independent marker for early disease relapse and disease-specific death in patients treated with surgery and radiotherapy, with an approximately 4-fold increased risk when compared to high K17 expression. Our results suggest a potential role for K17 and K19 expression profiles as tumor prognostic markers in OSCC patients. PMID:26634475

  16. Genetic markers: Potential candidates for cardiovascular disease.

    PubMed

    Rather, Riyaz Ahmad; Dhawan, Veena

    2016-10-01

    The effective prevention of cardiovascular disease depends upon the ability to recognize the high-risk individuals at an early stage of the disease or long before the development of adverse events. Evolving technologies in the fields of proteomics, metabolomics, and genomics have played a significant role in the discovery of cardiovascular biomarkers, but so far these methods have achieved the modest success. Hence, there is a crucial need for more reliable, suitable, and lasting diagnostic and therapeutic markers to screen the disease well in time to start the clinical aid to the patients. Gene polymorphisms associated with the cardiovascular disease play a decisive role in the disease onset. Therefore, the genetic marker evaluation to classify high-risk patients from low-risk patients trends an effective approach to patient management and care. Currently, there are no genetic markers available for extensive adoption as risk factors for coronary vascular disease, yet, there are numerous promising, biologically acceptable candidates. Many of these gene biomarkers, alone or in combination, can play an essential role in the prediction of cardiovascular risk. The present review highlights some putative emerging genetic biomarkers that could facilitate more authentic and fast diagnosis of CVD. This review also briefly describes few technological approaches employed in the biomarker search. PMID:27416153

  17. Expression of ABCG2 and Bmi-1 in oral potentially malignant lesions and oral squamous cell carcinoma.

    PubMed

    Dalley, Andrew J; Pitty, Luke P; Major, Aidan G; Abdulmajeed, Ahmad A; Farah, Camile S

    2014-04-01

    Early diagnosis is vital for effective treatment of oral squamous cell carcinoma (OSCC). The optimal time for clinical intervention is prior to malignancy when patients present with oral potentially malignant lesions such as leukoplakia or erythroplakia. Transformation rates for oral dysplasia vary greatly and more rigorous methods are needed to predict the malignant potential of oral lesions. We hypothesized that the expression of two putative stem cell markers, ABCG2 and Bmi-1, would correlate with disease severity for non diseased, potentially malignant and OSCC specimens and cell lines derived from an equivalent range of tissues. We compared immunoreactive protein and relative gene expression of ABCG2 and Bmi-1 in eight cell lines derived from source tissues ranging in disease severity from normal (OKF6-TERT2) through mild and moderate/severe dysplasia (DOK, POE-9n) to OSCC (PE/CA-PJ15, SCC04, SCC25, SCC09, SCC15). We also analyzed immunoreactive protein expression of ABCG2 and Bmi-1 in 189 tissue samples with the same range of disease severity. A trend between oral lesion severity to ABCG2 and Bmi-1 immunostain intensity was observed. Flow cytometry of oral cell lines confirmed this trend and gave good correlation with RT-PCR results for ABCG2 (r = 0.919, P = 0.001; Pearson) but not Bmi-1 (r = -0.311). The results provide evidence of increased density of ABCG2 and Bmi-1-positive populations in malignant and oral potentially malignant lesions and derived cell lines, but that intragroup variability within IHC, flow cytometry, and RT-PCR results compromise the diagnostic potential of these techniques for discriminating oral dysplasia from normal tissue or OSCC. PMID:24415717

  18. Poor oral health, a potential new geriatric syndrome.

    PubMed

    van der Putten, Gert-Jan; de Baat, Cees; De Visschere, Luc; Schols, Jos

    2014-02-01

    This article presents a brief introduction to the medical aspects of ageing and age-related diseases, and to some geriatric syndromes, followed by a discussion on their impact on general and oral healthcare provision to community-dwelling older people. Recent investigations suggest that inflammation constitutes a biological foundation of ageing and the onset of age-related diseases. Multimorbidity and polypharmacy, together with alterations in pharmacokinetics and pharmacodynamics, make older people at risk of adverse medication reactions. A side effect of several medications is causing xerostomia and hyposalivation, and both the type and number of medications used are relevant. New options of general healthcare provision to community-dwelling older people are the use of mobility aids and assistive technology devices, domiciliary health care, respite care and telecare. Their oral health status may be jeopardised by frailty, disability, care dependency and limited access to professional oral health care. Recommendations for improvement are the following: better integrating oral health care into general health care, developing and implementing an oral healthcare guideline, providing customised oral hygiene care aids, domiciliary oral healthcare provision, visiting dental hygienists and/or nurses, oral hygiene telecare, easily and safely accessible dental offices, transforming dentistry into medical oral health care and upgrading dentists to oral physicians. In case oral healthcare providers do not take the responsibility of persuading society of the importance of adequate oral health, weakened oral health of community-dwelling older people will become a potential new geriatric syndrome. PMID:24446975

  19. Potential prognostic, diagnostic and therapeutic markers for human gastric cancer

    PubMed Central

    Tsai, Ming-Ming; Wang, Chia-Siu; Tsai, Chung-Ying; Chi, Hsiang-Cheng; Tseng, Yi-Hsin; Lin, Kwang-Huei

    2014-01-01

    The high incidence of gastric cancer (GC) and its consequent mortality rate severely threaten human health. GC is frequently not diagnosed until a relatively advanced stage. Surgery is the only potentially curative treatment. Thus, early screening and diagnosis are critical for improving prognoses in patients with GC. Gastroscopy with biopsy is an appropriate method capable of aiding the diagnosis of specific early GC tumor types; however, the stress caused by this method together with it being excessively expensive makes it difficult to use it as a routine method for screening for GC on a population basis. The currently used tumor marker assays for detecting GC are simple and rapid, but their use is limited by their low sensitivity and specificity. In recent years, several markers have been identified and tested for their clinical relevance in the management of GC. Here, we review the serum-based tumor markers for GC and their clinical significance, focusing on discoveries from microarray/proteomics research. We also review tissue-based GC tumor markers and their clinical application, focusing on discoveries from immunohistochemical research. This review provides a brief description of various tumor markers for the purposes of diagnosis, prognosis and therapeutics, and we include markers already in clinical practice and various forthcoming biomarkers. PMID:25320517

  20. CD73 as a novel marker for poor prognosis of oral squamous cell carcinoma

    PubMed Central

    REN, ZHEN-HU; YUAN, YONG-XIANG; JI, TONG; ZHANG, CHEN-PING

    2016-01-01

    Ecto-5′-nucleotidase [cluster of differentiation (CD)73] has important functions in several types of cancer, however, its expression in squamous cell carcinoma (SCC) remains unknown. The present study was designed to investigate CD73 expression in SCC. CD73 expression was assessed by immunohistochemistry in 113 patients with oral SCC (OSCC). The association between CD73 expression and clinicopathological features, overall survival (OS) and disease-free survival (DFS) times of patients were statistically analyzed. CD73 expression was detected in 58.4% (66/113) of OSCC patients, with the immunostaining predominantly localized in the cytomembrane and a little in the cytoplasm. Statistical analysis revealed that CD73 expression was more frequently detected in patients with larger tumors (P=0.021). The overexpression of CD73 was significantly associated with clinical stage (P=0.047). Furthermore, immunohistochemical staining showed that overexpression of CD73 was inversely correlated with DFS (P=0.002) and OS (P=0.002) times. Multivariate Cox regression analysis revealed that CD73 expression was an independent prognostic factor for poor DFS (P=0.018) and OS (P=0.021). The current study is the first to evaluate the clinical significance and prognostic value of CD73 in patients with OSCC. The findings suggest that CD73 is a potential prognostic marker for OSCC. PMID:27347180

  1. Oral potentially malignant disorders in a large dental population

    PubMed Central

    Alessandro, VILLA; Anita, GOHEL

    2014-01-01

    Objectives Oral cancer (OC) may be preceded by clinically evident oral potentially malignant disorders (OPMDs). Oral carcinogenesis is a multistep process that begins as epithelial hyperplasia and progresses to oral epithelial dysplasia and finally to fully malignant phenotypes. The aim of our study was to estimate the prevalence of OPMDs in a large population of dental patients. Methods Patients were seen in the Oral Diagnosis and Oral Medicine clinics at Boston University Henry M. Goldman School of Dental Medicine between July 2013 and February 2014 and received a comprehensive oral examination to identify any possible mucosal lesions. Patients with a suspected OPMD (submucous fibrosis, oral lichen planus, leukoplakia and erythroplakia) that did not resolve in 2–3 weeks received a biopsy for definitive diagnosis. Logistic regression models were used to explore the relationship between OPMDs and associated risk factors. Results A total of 3,142 patients received a comprehensive oral examination [median age: 43 (range: 18–97); 54.3% females]. Among these, 4.5% had an oral mucosal lesion with 0.9% being an OPMD (one submucous fibrosis, three epithelial dysplasias, fourteen with hyperkeratosis/epithelial hyperplasia and nine with oral lichen planus). Males and current smokers were associated with higher odds of having OPMD (OR 1.7, 95% CI 0.8–3.8; OR 1.9, 95%CI 0.8–4.1). Increasing age was associated with having OPMDs (p<0.01). Conclusion Optimal oral visual screening for OC remains a simple and essential tool to identify any suspicious lesions and potentially increase survival. Although OPMDs were rare, our results confirm the importance of a thorough chairside screening by dentists and dental students to detect any mucosal changes. PMID:25591015

  2. Salivary markers of kidney function - Potentials and limitations.

    PubMed

    Celec, Peter; Tóthová, Ľubomíra; Šebeková, Katarína; Podracká, Ľudmila; Boor, Peter

    2016-01-30

    Saliva can be collected non-invasively, repeatedly and without trained personnel. It is a promising diagnostic body fluid with clinical use in endocrinology and dentistry. For decades, it is known that saliva contains also urea, creatinine and other markers of renal function. Clinical studies have shown that the salivary concentrations of these markers could be useful for the assessment of kidney function without the need of blood collection. This article summarizes the clinical and experimental data on the use of saliva as a diagnostic fluid in nephrology and points out the advantages, pitfalls, technical requirements and future perspective for the use of saliva as a novel potential diagnostic biofluid. PMID:26633856

  3. 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

  4. 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

  5. Single consumption of Bryndza cheese temporarily affects oral microbiota and salivary markers of oxidative stress.

    PubMed

    Kamodyová, Natália; Minárik, Gabriel; Hodosy, Július; Celec, Peter

    2014-11-01

    Several oral diseases are associated with changes in oral microbiota and higher oxidative stress. Enterococcus faecalis has been hypothesized to directly contribute to the oxidative stress in oral cavity. The aim of this study was to examine the effect of single consumption of unpasteurized Bryndza cheese containing enterococci on changes of microbiota and oxidative status in saliva. Fourteen healthy volunteers aged 23-30 years were asked to eat 100 g of Bryndza cheese. Saliva samples were collected before and 1, 10, 100 min, and 24 h after Bryndza cheese consumption. Species-specific PCR and terminal restriction fragment length polymorphism (T-RFLP) analysis were used to characterize oral microbiota. Markers of oxidative stress and antioxidant status were measured in saliva. PCR identified E. faecium in 36 % of probands saliva up to 1 day after consumption of enterococci containing Bryndza cheese. E. faecalis was detected in 57 % of probands saliva up to 10 min and in one proband up to 100 min after Bryndza cheese consumption. T-RFLP analysis confirmed short-term changes in composition of oral microbiota after Bryndza cheese ingestion. Nevertheless, the microbiota was completely restored after 24 h. One minute after ingestion of Bryndza cheese, salivary advanced oxidation protein products were significantly increased (by 74.6 %, P < 0.001), and total antioxidant capacity was decreased (by 22.0 %, P < 0.05). This study shows that single consumption of enterococci containing Bryndza cheese can temporally affect the composition of oral microbiota and oxidative stress in saliva. Further studies should identify the impact of these changes to the pathogenesis of oral diseases. PMID:24997802

  6. The prognostic value of immunohistochemical markers for oral tongue squamous cell carcinoma.

    PubMed

    Hwa, Jeong Seok; Kwon, Oh Jin; Park, Jung Je; Woo, Seung Hoon; Kim, Jin Pyeong; Ko, Gyung Hyuck; Seo, Ji Hyun; Kim, Rock Bum

    2015-10-01

    The objective of the study was to examine the prognostic value of hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase-IX (CA-IX), cyclooxygenase-2 (COX-2), Ki-67, and erythropoietin receptor in patients with oral tongue squamous cell carcinoma. Immunohistochemical analysis of marker expression was performed on tissue samples from 25 patients with tongue squamous cell carcinoma. The Kaplan-Meier method, univariate and multivariate analyses, and the Cox proportional hazards model were used to examine associations between patient and tumor characteristics, and the immunohistochemical results and disease-specific survival. There was no association between the expression of the five markers and disease-specific survival, and there was no statistically significant difference in the hazards ratio according to postoperative radiotherapy. There was no correlation between marker expression and prognosis. There was no association between marker expression and radioresistance or disease-specific survival. Therefore, HIF-1α, CA-IX, COX-2, Ki-67, and erythropoietin receptor are not suitable prognostic markers for tongue squamous cell carcinoma. PMID:25169079

  7. PDGFRβ Is a Novel Marker of Stromal Activation in Oral Squamous Cell Carcinomas

    PubMed Central

    Han, Rong; Haines, Paul; Gallagher, George; Noonan, Vikki; Kukuruzinska, Maria; Monti, Stefano; Trojanowska, Maria

    2016-01-01

    Carcinoma associated fibroblasts (CAFs) form the main constituents of tumor stroma and play an important role in tumor growth and invasion. The presence of CAFs is a strong predictor of poor prognosis of head and neck squamous cell carcinoma. Despite significant progress in determining the role of CAFs in tumor progression, the mechanisms contributing to their activation remain poorly characterized, in part due to fibroblast heterogeneity and the scarcity of reliable fibroblast surface markers. To search for such markers in oral squamous cell carcinoma (OSCC), we applied a novel approach that uses RNA-sequencing data derived from the cancer genome atlas (TCGA). Specifically, our strategy allowed for an unbiased identification of genes whose expression was closely associated with a set of bona fide stroma-specific transcripts, namely the interstitial collagens COL1A1, COL1A2, and COL3A1. Among the top hits were genes involved in cellular matrix remodeling and tumor invasion and migration, including platelet-derived growth factor receptor beta (PDGFRβ), which was found to be the highest-ranking receptor protein genome-wide. Similar analyses performed on ten additional TCGA cancer datasets revealed that other tumor types shared CAF markers with OSCC, including PDGFRβ, which was found to significantly correlate with the reference collagen expression in ten of the 11 cancer types tested. Subsequent immunostaining of OSCC specimens demonstrated that PDGFRβ was abundantly expressed in stromal fibroblasts of all tested cases (12/12), while it was absent in tumor cells, with greater specificity than other known markers such as alpha smooth muscle actin or podoplanin (3/11). Overall, this study identified PDGFRβ as a novel marker of stromal activation in OSCC, and further characterized a list of promising candidate CAF markers that may be relevant to other carcinomas. Our novel approach provides for a fast and accurate method to identify CAF markers without the need for

  8. PDGFRβ Is a Novel Marker of Stromal Activation in Oral Squamous Cell Carcinomas.

    PubMed

    Kartha, Vinay K; Stawski, Lukasz; Han, Rong; Haines, Paul; Gallagher, George; Noonan, Vikki; Kukuruzinska, Maria; Monti, Stefano; Trojanowska, Maria

    2016-01-01

    Carcinoma associated fibroblasts (CAFs) form the main constituents of tumor stroma and play an important role in tumor growth and invasion. The presence of CAFs is a strong predictor of poor prognosis of head and neck squamous cell carcinoma. Despite significant progress in determining the role of CAFs in tumor progression, the mechanisms contributing to their activation remain poorly characterized, in part due to fibroblast heterogeneity and the scarcity of reliable fibroblast surface markers. To search for such markers in oral squamous cell carcinoma (OSCC), we applied a novel approach that uses RNA-sequencing data derived from the cancer genome atlas (TCGA). Specifically, our strategy allowed for an unbiased identification of genes whose expression was closely associated with a set of bona fide stroma-specific transcripts, namely the interstitial collagens COL1A1, COL1A2, and COL3A1. Among the top hits were genes involved in cellular matrix remodeling and tumor invasion and migration, including platelet-derived growth factor receptor beta (PDGFRβ), which was found to be the highest-ranking receptor protein genome-wide. Similar analyses performed on ten additional TCGA cancer datasets revealed that other tumor types shared CAF markers with OSCC, including PDGFRβ, which was found to significantly correlate with the reference collagen expression in ten of the 11 cancer types tested. Subsequent immunostaining of OSCC specimens demonstrated that PDGFRβ was abundantly expressed in stromal fibroblasts of all tested cases (12/12), while it was absent in tumor cells, with greater specificity than other known markers such as alpha smooth muscle actin or podoplanin (3/11). Overall, this study identified PDGFRβ as a novel marker of stromal activation in OSCC, and further characterized a list of promising candidate CAF markers that may be relevant to other carcinomas. Our novel approach provides for a fast and accurate method to identify CAF markers without the need for

  9. Frequent detection of high human papillomavirus DNA loads in oral potentially malignant disorders.

    PubMed

    Pierangeli, A; Cannella, F; Scagnolari, C; Gentile, M; Sciandra, I; Antonelli, G; Ciolfi, C; Russo, C; Palaia, G; Romeo, U; Polimeni, A

    2016-01-01

    Human papillomavirus (HPV) is estimated to be the cause of 40--80% of the squamous cell carcinoma of the oropharynx but only of a small fraction of the oral cavity cancers. The prevalence of oral HPV infection has significantly increased in the last decade, raising concerns about the role of HPV in progression of oral potentially malignant disorders (OPMD) toward squamous cell carcinomas. We sought to study HPV infection in patients with oral lesions, and in control individuals, using non-invasive and site-specific oral brushing and sensitive molecular methods. HPV DNA positivity and viral loads were evaluated in relation to patient data and clinical diagnosis. We enrolled 116 individuals attending Dental Clinics: 62 patients with benign oral lesions (e.g. fibromas, papillomatosis, ulcers) or OPMD (e.g. lichen, leukoplakia) and 54 controls. Oral cells were collected with Cytobrush and HPV-DNA was detected with quantitative real-time PCR for the more common high-risk (HR) and low-risk (LR) genotypes. HPV detection rate, percentage of HR HPVs and HPV-DNA loads (namely HPV16 and in particular, HPV18) were significantly higher in patients than in controls. Lichen planus cases had the highest HPV-positive rate (75.0%), hairy leukoplakia the lowest (33.3%). This study detected unexpectedly high rates of HPV infection in cells of the oral mucosa. The elevated HR HPV loads found in OPMD suggest the effectiveness of quantitative PCR in testing oral lesions. Prospective studies are needed to establish whether elevated viral loads represent a clinically useful marker of the risk of malignant progression. PMID:26408278

  10. Evaluation of white blood cell count as a possible prognostic marker for oral cancer

    PubMed Central

    2011-01-01

    Introduction There seems to be increasing evidence that inflammation leads to cancer. For several cancers, an association with white blood cell (WBC) count has been reported. So far, no studies have been performed for cancer of the oral cavity and WBC. Therefore, the aim of the present study was to look at whether WBC count can be used as a prognostic marker for recurrence or metastases for oral cancer. Material and methods For 278 patients with oral cancer, the preoperative WBC count was compared with the clinicopathological information: age, gender, T-status, N-status, recurrence, metastases, follow-up time, and time till recurrence or metastases appeared. Results Out of 278 patients, 48 developed recurrence, 24 second tumors, 46 cervical metastases, and 14 distant metastases. The mean follow-up time was 35.97 months (range: 12-107 months). Significant Pearson correlation at the 0.05 level could be found for the T-status (0.046), but not for the N status (0.121). No significant correlation could be found between WBC count and the development of recurrence or metastases. Conclusion In conclusion, our findings demonstrate that elevated WBC count does not seem to be a predictor for recurrence or for further metastases. Further research is recommended to investigate the WBC count in precancerous lesions and in HPV positive patients with oral SCC. PMID:21352591

  11. New DNA methylation markers and global DNA hypomethylation are associated with oral cancer development.

    PubMed

    Foy, Jean-Philippe; Pickering, Curtis R; Papadimitrakopoulou, Vassiliki A; Jelinek, Jaroslav; Lin, Steven H; William, William N; Frederick, Mitchell J; Wang, Jing; Lang, Wenhua; Feng, Lei; Zhang, Li; Kim, Edward S; Fan, You H; Hong, Waun K; El-Naggar, Adel K; Lee, J Jack; Myers, Jeffrey N; Issa, Jean-Pierre; Lippman, Scott M; Mao, Li; Saintigny, Pierre

    2015-11-01

    DNA promoter methylation of tumor suppressor genes and global DNA hypomethylation are common features of head and neck cancers. Our goal was to identify early DNA methylation changes in oral premalignant lesions (OPL) that may serve as predictive markers of developing oral squamous cell carcinoma (OSCC). Using high-throughput DNA methylation profiles of 24 OPLs, we found that the top 86 genes differentially methylated between patients who did or did not develop OSCC were simultaneously hypermethylated, suggesting that a CpG island methylation phenotype may occur early during OSCC development. The vast majority of the 86 genes were nonmethylated in normal tissues and hypermethylated in OSCC versus normal mucosa. We used pyrosequencing in a validation cohort of 44 patients to evaluate the degree of methylation of AGTR1, FOXI2, and PENK promoters CpG sites that were included in the top 86 genes and of LINE1 repetitive element methylation, a surrogate of global DNA methylation. A methylation index was developed by averaging the percent methylation of AGTR1, FOXI2, and PENK promoters; patients with a high methylation index had a worse oral cancer-free survival (P = 0.0030). On the other hand, patients with low levels of LINE1 methylation had a significantly worse oral cancer-free survival (P = 0.0153). In conclusion, AGTR1, FOXI2, and PENK promoter methylation and LINE1 hypomethylation may be associated with an increased risk of OSCC development in patients with OPLs. PMID:26342026

  12. Potential markers of tongue tumor progression selected by cDNA microarray.

    PubMed

    Carinci, F; Lo Muzio, L; Piattelli, A; Rubini, C; Chiesa, F; Ionna, F; Palmieri, A; Maiorano, E; Pastore, A; Laino, G; Dolci, M; Pezzetti, F

    2005-01-01

    Squamous cell carcinoma (SCC), the most frequent malignant tumor of the oral cavity, generally exhibits a poor prognosis and metastases are the main cause of death. This tumor often arises from pre-malignant lesions. To date, it is difficult to predict if and which pre-malignant lesions may progress into oral SCC using traditional methods. For these reasons, several studies are trying to identify markers useful in the progression of pre-malignant lesions and tumors. To define the genetic expression profile of tongue tumor progression we compared 9 dysplasias (DS), 8 tumors without metastasis (TWM), 11 metastasizing SCCs (MT) of the tongue, and a baseline of 11 normal tissues by using cDNA microarray containing 19.2 K clones. We initially applied hierarchical agglomerative clustering based on information from all 6026 clones. Results were obtained by performing a two steps analysis: a Significance Analysis of Microarray (SAM) and a Gene Ontology search. One hundred and five clones have statistically significant different expression levels (FDR < 0.01) between DS and TWM, whereas 570 genes have statistically significant difference expression levels between TWM and MT (FDR < 0.01) as detected by SAM. By filtering with FatiGo only 33 genes were differentially expressed in TWN, respect to DS, whereas 155 genes were differentially expressed in MT respect to TWM. We detected some genes which encode for oncogenes, transcription factors and cell cycle regulators as potential markers of DS progression. Examples are BAG4, PAX3 and CCNI, respectively. Among potential markers of metastases are some genes related to cell mobility (TSPAN-2 and SNTA1), intercellular adhesion (integrin alpha 7) or extracellular matrix components (ADAMTS2 and cathepsin O). Additionally, under-expressed genes encoded apoptosis-related proteins (PDCD4 and CASP4). In conclusion, we identified several genes differentially expressed in tumor progression which can potentially help in better classifying

  13. 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

  14. 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

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

    PubMed Central

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

    2016-01-01

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

  16. 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

  17. Genomic Profiling of Advanced-Stage Oral Cancers Reveals Chromosome 11q Alterations as Markers of Poor Clinical Outcome

    PubMed Central

    Ambatipudi, Srikant; Gerstung, Moritz; Gowda, Ravindra; Pai, Prathamesh; Borges, Anita M.; Schäffer, Alejandro A.; Beerenwinkel, Niko; Mahimkar, Manoj B.

    2011-01-01

    Identifying oral cancer lesions associated with high risk of relapse and predicting clinical outcome remain challenging questions in clinical practice. Genomic alterations may add prognostic information and indicate biological aggressiveness thereby emphasizing the need for genome-wide profiling of oral cancers. High-resolution array comparative genomic hybridization was performed to delineate the genomic alterations in clinically annotated primary gingivo-buccal complex and tongue cancers (n = 60). The specific genomic alterations so identified were evaluated for their potential clinical relevance. Copy-number changes were observed on chromosomal arms with most frequent gains on 3q (60%), 5p (50%), 7p (50%), 8q (73%), 11q13 (47%), 14q11.2 (47%), and 19p13.3 (58%) and losses on 3p14.2 (55%) and 8p (83%). Univariate statistical analysis with correction for multiple testing revealed chromosomal gain of region 11q22.1–q22.2 and losses of 17p13.3 and 11q23–q25 to be associated with loco-regional recurrence (P = 0.004, P = 0.003, and P = 0.0003) and shorter survival (P = 0.009, P = 0.003, and P 0.0001) respectively. The gain of 11q22 and loss of 11q23-q25 were validated by interphase fluorescent in situ hybridization (I-FISH). This study identifies a tractable number of genomic alterations with few underlying genes that may potentially be utilized as biological markers for prognosis and treatment decisions in oral cancers. PMID:21386901

  18. Galectin-1 is a useful marker for detecting neoplastic squamous cells in oral cytology smears.

    PubMed

    Noda, Yuri; Kondo, Yuko; Sakai, Manabu; Sato, Sunao; Kishino, Mitsunobu

    2016-06-01

    Cytologic diagnoses in the oral region are very difficult due to the small amount of cells in smears, which are also exposed to many stimulating factors and often show atypical changes. Galectin-1 (Gal1) is a β-galactoside binding protein that modulates tumor progression. Gal1 is very weakly expressed in normal cells, but is often overexpressed in neoplastic lesions. The aim of the present study was to determine whether it is possible to differentiate reactive changes from neoplastic changes in oral cytology smears based on the expression of Gal1. A total of 155 tissue biopsy specimens and 61 liquid-based cytology specimens were immunostained by an anti-Gal1 antibody, and Gal1 expression levels were subsequently evaluated. These samples consisted of oral squamous cell carcinomas, epithelial dysplasia, and oral mucosal diseases. The positive and negative expressions of Gal1 were examined in 37 specimens collected by scalpel and cytobrush biopsy. The sensitivity, specificity, and positive predictive value of Gal1 were also evaluated in smears. In tissue sections, the positive ratio of Gal1 in neoplastic lesions was high (72.3%). In cytology specimens, the positive ratio of Gal1 was higher in neoplastic lesions (79.0%) than in those negative for intraepithelial lesion or malignancy (22.2%). A correlation was found between immunocytochemical Gal1 expression and immunohistochemical Gal1 expression (P < .001). The sensitivity (75.0%), specificity (75.0%), and positive predictive value (91.3%) of Gal1 were also high in smears. In conclusion, Gal1 may be a useful marker for determining whether morphologic changes in cells are reactive or neoplastic. PMID:26980012

  19. 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. PMID:26980956

  20. Predicting tumor metastasis in patients with oral cancer by means of the proliferation marker Ki67.

    PubMed

    Matsumoto, M; Komiyama, K; Okaue, M; Shimoyama, Y; Iwakami, K; Namaki, S; Tanaka, H; Moro, I; Sato, H

    1999-06-01

    Recent developments of a Ki67 antibody to recombinant parts of the Ki67 nuclear antigen have provided a marker for tumor proliferation. In the present study, biopsy specimens were obtained from 20 patents with squamous cell carcinoma of the oral cavity at various sites, who also received a regional neck dissection. The patients' mean age was 61 years. Normal mucosa obtained from the surgical materials of 10 patients with a non-tumor condition was also examined as a control. The expression of Ki67 was examined immunohistochemically and the labeling index (LI) assessed in the biopsy specimens. The patients were divided into two groups; patient who already had a regional lymph node metastasis at the time of tumor resection and patient without any metastasis. All of the oral carcinoma and normal mucosa specimens were positive for Ki67, while the magnitude of staining showed a wide variation. The median LI of the patients with metastasis and without metastasis was 37.63 +/- 8.30 and 20.40 +/- 4.22 respectively, while the normal mucosa control was 7.62 +/- 1.70. The results of this study suggest that an immunohistochemical examination of the biopsy materials for the Ki67 antigen and assessed LI index should prove useful for the prediction of lymph node metastasis. PMID:10453126

  1. Adiponectin and bone metabolism markers in female rowers: eumenorrheic and oral contraceptive users.

    PubMed

    Jürimäe, J; Vaiksaar, S; Mäestu, J; Purge, P; Jürimäe, T

    2011-12-01

    This study investigated whether adiponectin, bone formation (osteocalcin) and bone resorption [type I carboxyterminal telopeptide (ICTP)] values are influenced by menstrual cycle phase and oral contraceptive use in female rowers. Twenty-four rowers divided into normally cycling athletes (NOC; no.=15) and athletes taking oral contraceptive pills (OC; no.=9) participated in this study. Fasting blood samples, body composition and aerobic capacity measurements were taken during the follicular (FP) and the luteal (LP) phases of the menstrual cycle. Adiponectin, insulin, glucose, insulin resistance, body composition and aerobic capacity did not fluctuate significantly during menstrual cycle in both groups. Osteocalcin and ICTP were lower (p<0.05) in OC compared with NOC, but did not change significantly across menstrual cycle phases in both groups. Estradiol and progesterone were not related to adiponectin, osteocalcin or ICTP (r<0.147; p>0.05). Adiponectin was correlated (p<0.05) with osteocalcin (r=0.452) and fat free mass (r=0.428), and osteocalcin was related (p<0.05) to insulin (r=-0.413), glucose (r=-0.486) and insulin resistance (r=-0.528). In conclusion, adiponectin was not affected by menstrual cycle phase and OC use in female rowers, while bone metabolism markers were lower in OC compared to NOC groups. Adiponectin and osteocalcin were interrelated and may characterise energy homeostasis in female athletes. PMID:21169728

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

    PubMed

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

    2014-08-01

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

  3. 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

  4. Raman spectroscopy of oral tissues: correlation of spectral and biochemical markers

    NASA Astrophysics Data System (ADS)

    Singh, S. P.; Krishna, C. Murali

    2014-03-01

    Introduction Optical spectroscopic methods are being explored as novel tools for early and non-invasive cancer diagnosis. Both ex vivo and in vivo Raman spectroscopic studies carried out in oral cancer over the past decade have demonstrated that spectra of normal tissues are rich in lipids while tumor spectra show predominance of proteins. An accurate understanding of spectral features with respect to the biochemical composition is a pre-requisite before transferring these technologies for routine clinical usage. Therefore, in the present study, we have carried out Raman and biochemical studies on same tissues to correlate spectral markers and biochemical composition of normal and tumor oral tissues. Materials and Methods Spectra of 20 pairs of normal and tumor oral tissues were acquired using fiber-optic probe coupled HE-785 Raman spectrometer. Intensity associated with lipid (1440 cm-1) and protein (1450 and 1660 cm-1) bands were computed using curve-deconvolution method. Same tissues were then subjected to biochemical estimations of major biomolecules i.e., protein, lipid and phospholipids. Results and Discussion The intensity of the lipid band was found to be higher in normal tissues with respect to tumors, and the protein band was higher in tumors compared to normal tissues. Biochemical estimation yielded similar results i.e. high protein to lipid or phospholipid ratio in tumors with-respect to normal tissues. These differences were found to be statistically significant. Conclusion Findings of curve-deconvolution and biochemical estimation correlate very well and corroborate the spectral profile noted in earlier studies.

  5. Protein-bound acrolein: Potential markers for oxidative stress

    PubMed Central

    Uchida, Koji; Kanematsu, Masamichi; Sakai, Kensuke; Matsuda, Tsukasa; Hattori, Nobutaka; Mizuno, Yoshikuni; Suzuki, Daisuke; Miyata, Toshio; Noguchi, Noriko; Niki, Etsuo; Osawa, Toshihiko

    1998-01-01

    Acrolein (CH2=CH—CHO) is known as a ubiquitous pollutant in the environment. Here we show that this notorious aldehyde is not just a pollutant, but also a lipid peroxidation product that could be ubiquitously generated in biological systems. Upon incubation with BSA, acrolein was rapidly incorporated into the protein and generated the protein-linked carbonyl derivative, a putative marker of oxidatively modified proteins under oxidative stress. To verify the presence of protein-bound acrolein in vivo, the mAb (mAb5F6) against the acrolein-modified keyhole limpet hemocyanin was raised. It was found that the acrolein-lysine adduct, Nɛ-(3-formyl-3,4-dehydropiperidino)lysine, constitutes an epitope of the antibody. Immunohistochemical analysis of atherosclerotic lesions from a human aorta demonstrated that antigenic materials recognized by mAb5F6 indeed constituted the lesions, in which intense positivity was associated primarily with macrophage-derived foam cells and the thickening neointima of arterial walls. The observations that (i) oxidative modification of low-density lipoprotein with Cu2+ generated the acrolein-low-density lipoprotein adducts and (ii) the iron-catalyzed oxidation of arachidonate in the presence of protein resulted in the formation of antigenic materials suggested that polyunsaturated fatty acids are sources of acrolein that cause the production of protein-bound acrolein. These data suggest that the protein-bound acrolein represents potential markers of oxidative stress and long-term damage to protein in aging, atherosclerosis, and diabetes. PMID:9560197

  6. A Comparative Study of the Oral Proficiency of Chinese Learners of English across Task Functions: A Discourse Marker Perspective

    ERIC Educational Resources Information Center

    Wei, Ming

    2011-01-01

    This study investigated the use of discourse markers (DMs) by college learners of English in China. It compared the use of DMs for four discourse functions by students at different proficiency levels. An audio-video instrument called Video Oral Communication Instrument was conducted to elicit ratable speech samples. Fraser's (1999) taxonomy was…

  7. Network analysis reveals potential markers for pediatric adrenocortical carcinoma

    PubMed Central

    Kulshrestha, Anurag; Suman, Shikha; Ranjan, Rakesh

    2016-01-01

    Pediatric adrenocortical carcinoma (ACC) is a rare malignancy with a poor outcome. Molecular mechanisms of pediatric ACC oncogenesis and advancement are not well understood. Accurate and timely diagnosis of the disease requires identification of new markers for pediatric ACC. Differentially expressed genes (DEGs) were identified from the gene expression profile of pediatric ACC and obtained from Gene Expression Omnibus. Gene Ontology functional and pathway enrichment analysis was implemented to recognize the functions of DEGs. A protein–protein interaction (PPI) and gene–gene functional interaction (GGI) network of DEGs was constructed. Hub gene detection and enrichment analysis of functional modules were performed. Furthermore, a gene regulatory network incorporating DEGs–microRNAs–transcription factors was constructed and analyzed. A total of 431 DEGs including 228 upregulated and 203 downregulated DEGs were screened. These genes were largely involved in cell cycle, steroid biosynthesis, and p53 signaling pathways. Upregulated genes, CDK1, CCNB1, CDC20, and BUB1B, were identified as the common hubs of PPI and GGI networks. All the four common hub genes were also part of modules of the PPI network. Moreover, all the four genes were also present in the largest module of GGI network. A gene regulatory network consisting of 82 microRNAs and 100 transcription factors was also constructed. CDK1, CCNB1, CDC20, and BUB1B may serve as potential biomarker of pediatric ACC and as potential targets for therapeutic approach, although experimental studies are required to authenticate our findings. PMID:27555782

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

    PubMed

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

    2016-08-01

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

  9. Oral Bacteria as Potential Probiotics for the Pharyngeal Mucosa▿

    PubMed Central

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

    2010-01-01

    The research described here was aimed at the selection of oral bacteria that displayed properties compatible with their potential use as probiotics for the pharyngeal mucosa. We included in the study 56 bacteria newly isolated from the pharynges of healthy donors, which were identified at the intraspecies level and characterized in vitro for their probiotic potential. The experiments led us to select two potential probiotic bacterial strains (Streptococcus salivarius RS1 and ST3) and to compare them with the prototype oral probiotic S. salivarius strain K12. All three strains efficiently bound to FaDu human epithelial pharyngeal cells and thereby antagonized Streptococcus pyogenes adhesion and growth. All were sensitive to a variety of antibiotics routinely used for the control of upper respiratory tract infections. Immunological in vitro testing on a FaDu layer revealed different responses to RS1, ST3, and K12. RS1 and ST3 modulated NF-κB activation and biased proinflammatory cytokines at baseline and after interleukin-1β (IL-1β) induction. In conclusion, we suggest that the selected commensal streptococci represent potential pharyngeal probiotic candidates. They could display a good degree of adaptation to the host and possess potential immunomodulatory and anti-inflammatory properties. PMID:20418429

  10. Gastric cancer stem cells: evidence, potential markers, and clinical implications.

    PubMed

    Brungs, Daniel; Aghmesheh, Morteza; Vine, Kara L; Becker, Therese M; Carolan, Martin G; Ranson, Marie

    2016-04-01

    Gastric cancer is a significant global health problem. It is the fifth most common cancer and third leading cause of cancer-related death worldwide (Torre et al. in CA Cancer J Clin 65(2):87-108, 2015). Despite advances in treatment, overall prognosis remains poor, due to tumour relapse and metastasis. There is an urgent need for novel therapeutic approaches to improve clinical outcomes in gastric cancer. The cancer stem cell (CSC) model has been proposed to explain the high rate of relapse and subsequent resistance of cancer to current systemic treatments (Vermeulen et al. in Lancet Oncol 13(2):e83-e89, 2012). CSCs have been identified in many solid malignancies, including gastric cancer, and have significant clinical implications, as targeting the CSC population may be essential in preventing the recurrence and spread of a tumour (Dewi et al. in J Gastroenterol 46(10):1145-1157, 2011). This review seeks to summarise the current evidence for CSC in gastric cancer, with an emphasis on candidate CSC markers, clinical implications, and potential therapeutic approaches. PMID:26428661

  11. Markers

    ERIC Educational Resources Information Center

    Healthy Schools Network, Inc., 2011

    2011-01-01

    Dry erase whiteboards come with toxic dry erase markers and toxic cleaning products. Dry erase markers labeled "nontoxic" are not free of toxic chemicals and can cause health problems. Children are especially vulnerable to environmental health hazards; moreover, schools commonly have problems with indoor air pollution, as they are more densely…

  12. Prognostic potential of AgNORs in oral submucous fibrosis

    PubMed Central

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

    2016-01-01

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

  13. 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.

  14. DNA methylation markers for oral pre-cancer progression: A critical review

    PubMed Central

    Shridhar, Krithiga; Walia, Gagandeep Kaur; Aggarwal, Aastha; Gulati, Smriti; Geetha, A.V.; Prabhakaran, Dorairaj; Dhillon, Preet K.; Rajaraman, Preetha

    2016-01-01

    Summary Although oral cancers are generally preceded by a well-established pre-cancerous stage, there is a lack of well-defined clinical and morphological criteria to detect and signal progression from pre-cancer to malignant tumours. We conducted a critical review to summarize the evidence regarding aberrant DNA methylation patterns as a potential diagnostic biomarker predicting progression. We identified all relevant human studies published in English prior to 30th April 2015 that examined DNA methylation (%) in oral pre-cancer by searching PubMed, Web-of-Science and Embase databases using combined key-searches. Twenty-one studies (18-cross-sectional; 3-longitudinal) were eligible for inclusion in the review, with sample sizes ranging from 4 to 156 affected cases. Eligible studies examined promoter region hyper-methylation of tumour suppressor genes in pathways including cell-cycle-control (n = 15), DNA-repair (n = 7), cell-cycle-signalling (n = 4) and apoptosis (n = 3). Hyper-methylated loci reported in three or more studies included p16, p14, MGMT and DAPK. Two longitudinal studies reported greater p16 hyper-methylation in pre-cancerous lesions transformed to malignancy compared to lesions that regressed (57–63.6% versus 8–32.1%; p < 0.01). The one study that explored epigenome-wide methylation patterns reported three novel hyper-methylated loci (TRHDE; ZNF454; KCNAB3). The majority of reviewed studies were small, cross-sectional studies with poorly defined control groups and lacking validation. Whilst limitations in sample size and study design preclude definitive conclusions, current evidence suggests a potential utility of DNA methylation patterns as a diagnostic biomarker for oral pre-cancer progression. Robust studies such as large epigenome-wide methylation explorations of oral pre-cancer with longitudinal tracking are needed to validate the currently reported signals and identify new risk-loci and the biological pathways of disease

  15. Data defining markers of human neural stem cell lineage potential

    PubMed Central

    Oikari, Lotta E.; Okolicsanyi, Rachel K.; Griffiths, Lyn R.; Haupt, Larisa M.

    2016-01-01

    Neural stem cells (NSCs) and neural progenitor cells (NPCs) are self-renewing and multipotent cells, however, NPCs are considered to be more lineage-restricted with a reduced self-renewing capacity. We present data comparing the expression of 21 markers encompassing pluripotency, self-renewal (NSC) as well as neuronal and glial (astrocyte and oligodendrocyte) lineage specification and 28 extracellular proteoglycan (PG) genes and their regulatory enzymes between embryonic stem cell (ESC)-derived human NSCs (hNSC H9 cells, Thermo Fisher) and human cortex-derived normal human NPCs (nhNPCs, Lonza). The data demonstrates expression differences of multiple lineage and proteoglycan-associated genes between hNSC H9 cells and nhNPCs. Data interpretation of markers and proteoglycans defining NSC and neural cell lineage characterisation can be found in “Cell surface heparan sulfate proteoglycans as novel markers of human neural stem cell fate determination” (Oikari et al. 2015) [1]. PMID:26958640

  16. Data defining markers of human neural stem cell lineage potential.

    PubMed

    Oikari, Lotta E; Okolicsanyi, Rachel K; Griffiths, Lyn R; Haupt, Larisa M

    2016-06-01

    Neural stem cells (NSCs) and neural progenitor cells (NPCs) are self-renewing and multipotent cells, however, NPCs are considered to be more lineage-restricted with a reduced self-renewing capacity. We present data comparing the expression of 21 markers encompassing pluripotency, self-renewal (NSC) as well as neuronal and glial (astrocyte and oligodendrocyte) lineage specification and 28 extracellular proteoglycan (PG) genes and their regulatory enzymes between embryonic stem cell (ESC)-derived human NSCs (hNSC H9 cells, Thermo Fisher) and human cortex-derived normal human NPCs (nhNPCs, Lonza). The data demonstrates expression differences of multiple lineage and proteoglycan-associated genes between hNSC H9 cells and nhNPCs. Data interpretation of markers and proteoglycans defining NSC and neural cell lineage characterisation can be found in "Cell surface heparan sulfate proteoglycans as novel markers of human neural stem cell fate determination" (Oikari et al. 2015) [1]. PMID:26958640

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

    PubMed

    Luo, Yangchao; Pan, Kang; Zhong, Qixin

    2015-01-01

    Delivery systems prepared with natural biopolymers are of particular interests for applications in food, pharmaceutics and biomedicine. In this study, nanocomplex particles of sodium caseinate (NaCas) and pectin were fabricated and investigated as potential oral delivery vehicles. Nanocomplexes were prepared with three mass ratios of NaCas/pectin by acidification using glucono-δ-lactone and thermal treatment. NaCas/pectin at 1:1 mass ratio resulted in dispersions with the lowest turbidity and the smallest and most uniform nanocomplexes. Thermal treatment at 85 °C for 30 min facilitated the formation of stable, compact, and spherical nanocomplexes. Heating not only greatly increased the yield of nanocomplexes but also significantly improved the encapsulation capability of rutin studied as a model compound. Pectin in nanocomplexes delayed the hydrolysis of NaCas by pepsin at gastric conditions and enabled the controlled release of most rutin in simulated intestinal conditions. The nanocomplexes based on food-sourced biopolymers have promising features for oral delivery of nutrients and medicines. PMID:25800678

  18. Gene expression profiling of craniofacial fibrous dysplasia reveals ADAMTS2 overexpression as a potential marker.

    PubMed

    Zhou, Shang-Hui; Yang, Wen-Jun; Liu, Sheng-Wen; Li, Jiang; Zhang, Chun-Ye; Zhu, Yun; Zhang, Chen-Ping

    2014-01-01

    Fibrous dysplasia (FD) as an abnormal bone growth is one of the common fibro-osseous leasions (FOL) in oral and maxillofacial region, however, its etiology still remains unclear. Here, we performed gene expression profiling of FD using microarray analysis to explore the key molecule events in FD development, and develop potential diagnostic markers or therapeutic targets for FD. We found that 1,881 genes exhibited differential expression with more than two-fold changes in FD compared to normal bone tissues, including 1,200 upregulated genes and 681 downregulated genes. Pathway analysis indicated that obviously activated pathways are Ribosome and ECM-receptor interaction pathways; downregulated pathways are "Hepatitis C" and "cancer" signaling pathways. We further validated the expression of ADAMTS2, one of most differentiated expressed genes, by Immunohistochemistry (IHC) in 40 of FD cases. Results showed that ADAMTS2 was significantly overexpressed in FD tissues, but rarely expressed in normal bone tissues, suggesting that ADAMTS2 could be a potential biomarker for FD. Thus, this study uncovered differentially expressed candidate genes in FD, which provides pilot data for understanding FD pathogenesis, and developing novel biomarkers for diagnosis and targeting of FD. PMID:25674217

  19. Gene expression profiling of craniofacial fibrous dysplasia reveals ADAMTS2 overexpression as a potential marker

    PubMed Central

    Zhou, Shang-Hui; Yang, Wen-Jun; Liu, Sheng-Wen; Li, Jiang; Zhang, Chun-Ye; Zhu, Yun; Zhang, Chen-Ping

    2014-01-01

    Fibrous dysplasia (FD) as an abnormal bone growth is one of the common fibro-osseous leasions (FOL) in oral and maxillofacial region, however, its etiology still remains unclear. Here, we performed gene expression profiling of FD using microarray analysis to explore the key molecule events in FD development, and develop potential diagnostic markers or therapeutic targets for FD. We found that 1,881 genes exhibited differential expression with more than two-fold changes in FD compared to normal bone tissues, including 1,200 upregulated genes and 681 downregulated genes. Pathway analysis indicated that obviously activated pathways are Ribosome and ECM-receptor interaction pathways; downregulated pathways are “Hepatitis C” and “cancer” signaling pathways. We further validated the expression of ADAMTS2, one of most differentiated expressed genes, by Immunohistochemistry (IHC) in 40 of FD cases. Results showed that ADAMTS2 was significantly overexpressed in FD tissues, but rarely expressed in normal bone tissues, suggesting that ADAMTS2 could be a potential biomarker for FD. Thus, this study uncovered differentially expressed candidate genes in FD, which provides pilot data for understanding FD pathogenesis, and developing novel biomarkers for diagnosis and targeting of FD. PMID:25674217

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

    PubMed Central

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

    2011-01-01

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

  1. 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

  2. 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

  3. Analysis of the invasive edge in primary and secondary oral squamous cell carcinoma: An independent prognostic marker: A retrospective study

    PubMed Central

    Nadaf, Afreen; Bavle, Radhika M; Soumya, M; D'mello, Sarah; Kuriakose, Moni Abraham; Govindan, Sindhu

    2016-01-01

    Background and Objectives: Oral squamous cell carcinoma (OSCC) is one of the most common head and neck carcinomas and corresponds to 95% of all oral cancers with an increasing morbidity and mortality. Its prognosis is affected by several clinicopathologic factors, one of which is pattern of invasion (POI). The histological features of OSCC may differ widely, but there is general agreement that the most useful prognostic information can be deduced from the invasive front of the tumor. In this retrospective study, our aim was to compare the POI, the status of connective tissue and the status of inflammation at the tumor–host interface in primary and recurrent (secondary) OSCC and test the validity of POI, to serve as a potential marker to assess the prognosis of the patient. Materials and Methods: Differentiation of tumors, POI, status of connective tissue and inflammation was assessed in 168 cases of primary and recurrent cases of OSCC. Statistical Analysis: Fisher's exact test was used to determine the statistical significance and P < 0.05 was considered to be statistically significant. Results: Our study showed that majority of the primary and secondary tumors were well differentiated, 117 [95.9%] and 34 [73.9%], respectively. Predominant POI in the primary and secondary tumor group was Pattern II and least was Pattern V. Worst pattern in primary tumor and highest distribution was seen for Pattern III (53.3%), and least for Pattern V (0.00%). In secondary tumors, the predominant worst pattern was Pattern IV (50.0%) and least distribution was seen for Pattern I (0.00%). Connective tissue status for both primary and secondary tumors showed the predominance of loose type (85.2% and 79.2%) and least was variable type (0.8% and 0.6%), respectively. Status of inflammation in the primary tumor group showed a predominance of moderate grade of inflammation (50.0%) and very mild grade of inflammation (6.6%) was the least type. In the secondary tumor group, moderate grade

  4. 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

  5. Folate-homocysteine interrelations: potential new markers of folate status.

    PubMed

    Lucock, M D; Daskalakis, I; Schorah, C J; Lumb, C H; Oliver, M; Devitt, H; Wild, J; Dowell, A C; Levene, M I

    1999-05-01

    We report a transient drop in plasma Hcy and Cys following a single oral dose of PteGlu. The thiol change was concomitant with both the peak plasma 5CH3H4PteGlu1 level (by HPLC) and the maximum plasma Lactobacillus casei activity which reflects absorption of unmodified PteGlu. The significant reciprocal association of Hcy with radioassay RBC folate (r = -0.28, 99% CI -0.48, -0.05, P = 0.0016), serum folate (r = -0.37, 99% CI -0.56, -16, P = 0.0001), and vitamin B12 (r = -0.42, 99% CI -0.59, -21, P = 0.0001) is shown and reflects the long-term nutritional effect of B vitamins on this important, potentially atherogenic thiol. These are now well-established associations. We extend the potential for investigation of folate metabolism in health and disease by evaluating a range of new folate indices which are based on erythrocyte coenzymes. These have been looked at independently and in association with established parameters. Erythrocyte methylfolates (mono- to hexaglutamate-5CH3H4PteGlu1-6), formylfolates (tri- to pentaglutamate-5CHOH4PteGlu3-5),formiminotetrahydrofolate (formiminoH4PteGlu1), unsubstituted tetrahydrofolate (H4PteGlu1), andpara-aminobenzoylglutamate (P-ABG) have been measured by HPLC with fluorescence detection. A positive linear association exists between (i) H4PteGlu1 and radioassay RBC folate (r = 0.50, 99% CI 0. 07, 0.77, P = 0.0036), and (ii) H4PteGlu1 and tetraglutamates of both formyl- and methylfolate (r = 0.52, 99% CI 0.10, 0.78, P = 0. 0022, and r = 0.56, 99% CI 0.15, 0.80, P = 0.0009, respectively). Since, in addition, a reciprocal linear association exists between Hcy and tetraglutamyl formylfolate (r = -0.41, 99% CI -0.73, 0.05, P = 0.0206), erythrocyte tetraglutamates may be a good reflection of the bodies' active coenzyme pools. Pentaglutamyl formylfolate, the longest oligo-gamma-glutamyl chain form of this coenzyme may be a good indicator of folate depletion. The abundance of this coenzyme both increases with increasing Hcy (r = 0

  6. 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

  7. Advances in Carcinogenic Metal Toxicity and Potential Molecular Markers

    PubMed Central

    Koedrith, Preeyaporn; Seo, Young Rok

    2011-01-01

    Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classified as carcinogens affecting human health through occupational and environmental exposure. However, the underlying mechanisms involved in tumor formation are not well clarified. Interference of metal homeostasis may result in oxidative stress which represents an imbalance between production of free radicals and the system’s ability to readily detoxify reactive intermediates. This event consequently causes DNA damage, lipid peroxidation, protein modification, and possibly symptomatic effects for various diseases including cancer. This review discusses predominant modes of action and numerous molecular markers. Attention is paid to metal-induced generation of free radicals, the phenomenon of oxidative stress, damage to DNA, lipid, and proteins, responsive signal transduction pathways with major roles in cell growth and development, and roles of antioxidant enzymatic and DNA repair systems. Interaction of non-enzymatic antioxidants (carotenoids, flavonoids, glutathione, selenium, vitamin C, vitamin E, and others) with cellular oxidative stress markers (catalase, glutathione peroxidase, and superoxide dismutase) as well as certain regulatory factors, including AP-1, NF-κB, Ref-1, and p53 is also reviewed. Dysregulation of protective pathways, including cellular antioxidant network against free radicals as well as DNA repair deficiency is related to oncogenic stimulation. These observations provide evidence that emerging oxidative stress-responsive regulatory factors and DNA repair proteins are putative predictive factors for tumor initiation and progression. PMID:22272150

  8. A comparison of oral and intravenous pimonidazole in canine tumors using intravenous CCI-103F as a control hypoxia marker

    SciTech Connect

    Kleiter, Miriam M.; Thrall, Donald E.; Malarkey, David E.; Ji Xiaoshen; Lee, David Y.W.; Chou, S.-C.; Raleigh, James A. . E-mail: james_raleigh@med.unc.edu

    2006-02-01

    Purpose: Pimonidazole HCl is widely used in immunohistochemical analyses of hypoxia in normal and malignant tissues. The present study investigates oral administration as a means of minimizing invasiveness. Methods and Materials: Twelve dogs with confirmed malignancy received 0.5 g/m{sup 2} of pimonidazole HCl: 6 by mouth and 6 by i.v. infusion. All dogs received i.v. CCI-103F as a control. Plasma levels of pimonidazole, pimonidazole N-oxide, and CCI-103F were measured. Tumor biopsies were formalin fixed, paraffin embedded, sectioned, immunostained, and analyzed for pimonidazole and CCI-103F binding. pH dependence for pimonidazole and CCI-103F binding was studied in vitro. Results: Pimonidazole and CCI-103F binding in carcinomas and sarcomas was strongly correlated for both oral and i.v. pimonidazole HCl (r {sup 2} = 0.97). On average, the extent of pimonidazole binding exceeded that for CCI-103F by a factor of approximately 1.2, with the factor ranging from 1.0 to 1.65. Binding of both markers was pH dependent, but pimonidazole binding was greater at all values of pH. Conclusions: Oral pimonidazole HCl is effective as a hypoxia marker in spontaneously arising canine tumors. Selective cellular uptake and concomitant higher levels of binding in regions of hypoxia at the high end of pH gradients might account for the greater extent of pimonidazole binding.

  9. Orality, Literacy and Music's Creative Potential: A Comparative Approach.

    ERIC Educational Resources Information Center

    Campbell, Patricia Shehan

    1989-01-01

    Describes the rise of musical notation in the West, showing the relationship between that development and the origin of music literacy in China. Suggests that the balance of oral and literate means of music learning may foster creative expression in performance. Encourages the study and practice of orality in the training of young musicians. (LS)

  10. 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

  11. Identification of Mesenchymal Stem Cell Marker STRO-1 in Oral Reactive Lesions by Immunofluorescence Method

    PubMed Central

    Dehghani Nazhvani, Ali; Hosseini, Seyed-Mojtaba; Tahoori, Bita; Tavangar, Maryam-Sadat; Attar, Armin

    2015-01-01

    Statement of the Problem Stem cells are considered as new implement for tissue regeneration. Several niches in adult human body are colonized by multipotent stem cells but access to these potential reservoirs is often limited. Although human dental pulp stem cells isolated from healthy teeth have been extensively characterized, it is still unknown whether stem cells also exist in reactive lesions of oral cavity such as pyogenic granuloma and peripheral ossifying fibroma which are deliberated as inflammatory proliferation of different cell families. Purpose The aim of this study was to explore for clues to see whether pyogenic granuloma or peripheral ossifying fibroma contain dental mesenchymal stem cell (DMSC). Materials and Method Four pyogenic granuloma and four peripheral ossifying fibroma specimens were collected by excisional biopsy and preserved in PBS-EDTA at -86 °C. Then we cut them in 5µm diameter using Cryostat. Having been rinsed with PBS, the samples were stained with a primary mouse anti-human STRO-1 monoclonal IgM antibody. Afterward, a secondary goat anti-mouse IgM-FITC antibody was applied to detect STRO-1+ cells as probable stem cells by immunofluorescence technique. Results Immunofluorescence microscopy revealed presence of STRO-1+ cells in these lesions, particularly localized on perivascular zone. The negative control group was not glowing. Conclusion Based on these results, it was found that reactive lesions of pyogenic granuloma and peripheral ossifying fibroma have STRO-1 positive cells, which raises the possibility that these cells may be DMSCs. PMID:26535404

  12. Cellular Distribution and Gene Expression Pattern of Metastasin (S100A4), Calgranulin A (S100A8), and Calgranulin B (S100A9) in Oral Lesions as Markers for Molecular Pathology.

    PubMed

    Reckenbeil, Jan; Kraus, Dominik; Probstmeier, Rainer; Allam, Jean-Pierre; Novak, Natalija; Frentzen, Matthias; Martini, Markus; Wenghoefer, Matthias; Winter, Jochen

    2016-07-01

    The objective of this study was to analyze cellular localization and expression levels of oncologic relevant members of the S100 family in common oral lesions.Biopsies of various oral lesions were analyzed. S100A4 showed a higher expression rate in leukoplakias and oral squamous cell carcinomas. Transcript levels of S100A8 and S100A9 were significantly decreased in malignant OSCCs. A correlation could be drawn between the expression levels of these genes and the pathological characteristics of the investigated lesions. S100A4, A8, and A9 proteins represent promising marker genes to evaluate the risk potential of suspicious oral lesions in molecular pathology. PMID:27294692

  13. 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

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

    PubMed

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

    2015-02-01

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

  15. 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

  16. Oral potentially malignant disorders: an overview of more than 20 entities.

    PubMed

    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

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

    PubMed

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

    2016-01-01

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

  18. Rad6 is a Potential Early Marker of Melanoma Development

    PubMed Central

    Rosner, Karli; Adsule, Shreelekha; Haynes, Brittany; Kirou, Evangelia; Kato, Ikuko; Mehregan, Darius R.; Shekhar, Malathy P.V.

    2014-01-01

    Melanoma is the leading cause of death from skin cancer in industrialized countries. Several melanoma-related biomarkers and signaling pathways have been identified; however, their relevance to melanoma development/progression or to clinical outcome remains to be established. Aberrant activation of Wnt/β-catenin pathway is implicated in various cancers including melanoma. We have previously demonstrated Rad6, an ubiquitin-conjugating enzyme, as an important mediator of β-catenin stability in breast cancer cells. Similar to breast cancer, β-catenin-activating mutations are rare in melanomas, and since β-catenin signaling is implicated in melanoma, we examined the relationship between β-catenin levels/activity and expression of β-catenin transcriptional targets Rad6 and microphthalmia-associated transcription factor-M (Mitf-M) in melanoma cell models, and expression of Rad6, β-catenin, and Melan-A in nevi and cutaneous melanoma tissue specimens. Our data show that Rad6 is only weakly expressed in normal human melanocytes but is overexpressed in melanoma lines. Unlike Mitf-M, Rad6 overexpression in melanoma lines is positively associated with high molecular weight β-catenin protein levels and β-catenin transcriptional activity. Double-immunofluorescence staining of Rad6 and Melan-A in melanoma tissue microarray showed that histological diagnosis of melanoma is significantly associated with Rad6/Melan-A dual positivity in the melanoma group compared to the nevi group (P = .0029). In contrast to strong β-catenin expression in normal and tumor areas of superficial spreading malignant melanoma (SSMM), Rad6 expression is undetectable in normal areas and Rad6 expression increases coincide with increased Melan-A in the transformed regions of SSMM. These data suggest a role for Rad6 in melanoma pathogenesis and that Rad6 expression status may serve as an early marker for melanoma development. PMID:24831578

  19. Rad6 is a Potential Early Marker of Melanoma Development.

    PubMed

    Rosner, Karli; Adsule, Shreelekha; Haynes, Brittany; Kirou, Evangelia; Kato, Ikuko; Mehregan, Darius R; Shekhar, Malathy P V

    2014-05-12

    Melanoma is the leading cause of death from skin cancer in industrialized countries. Several melanoma-related biomarkers and signaling pathways have been identified; however, their relevance to melanoma development/progression or to clinical outcome remains to be established. Aberrant activation of Wnt/β-catenin pathway is implicated in various cancers including melanoma. We have previously demonstrated Rad6, an ubiquitin-conjugating enzyme, as an important mediator of β-catenin stability in breast cancer cells. Similar to breast cancer, β-catenin-activating mutations are rare in melanomas, and since β-catenin signaling is implicated in melanoma, we examined the relationship between β-catenin levels/activity and expression of β-catenin transcriptional targets Rad6 and microphthalmia-associated transcription factor-M (Mitf-M) in melanoma cell models, and expression of Rad6, β-catenin, and Melan-A in nevi and cutaneous melanoma tissue specimens. Our data show that Rad6 is only weakly expressed in normal human melanocytes but is overexpressed in melanoma lines. Unlike Mitf-M, Rad6 overexpression in melanoma lines is positively associated with high molecular weight β-catenin protein levels and β-catenin transcriptional activity. Double-immunofluorescence staining of Rad6 and Melan-A in melanoma tissue microarray showed that histological diagnosis of melanoma is significantly associated with Rad6/Melan-A dual positivity in the melanoma group compared to the nevi group (P=.0029). In contrast to strong β-catenin expression in normal and tumor areas of superficial spreading malignant melanoma (SSMM), Rad6 expression is undetectable in normal areas and Rad6 expression increases coincide with increased Melan-A in the transformed regions of SSMM. These data suggest a role for Rad6 in melanoma pathogenesis and that Rad6 expression status may serve as an early marker for melanoma development. PMID:24831578

  20. Lipid Profile and Oxidative Stress Markers in Wistar Rats following Oral and Repeated Exposure to Fijk Herbal Mixture

    PubMed Central

    Adeyemi, Oluyomi Stephen; Orekoya, Bukola Temitope

    2014-01-01

    This study determined the effect of the oral and repeated administration of Fijk herbal mixture on rat biochemical and morphological parameters. Twenty-four Wistar rats were distributed into four groups of 6. Group A served as control and received oral administration of distilled water daily. The experimental groups B, C, and D were daily and orally exposed to Fijk herbal mixture at 15, 30, and 45 mg/kg, respectively. Treatments lasted for 21 days. The rats were sacrificed under mild diethyl ether anesthesia 24 hr after cessation of treatment. The blood and liver samples were collected and used for the biochemical and morphological analyses. Oral exposure to Fijk caused elevated levels of rat plasma ALT, AST, triglycerides, LDL, and MDA. In contrast, rat plasma HDL, GSH, and ALP levels were lowered by Fijk oral exposure. Also, the herbal remedy caused a dose-dependent elevation in the plasma atherogenic index. The histopathology examinations of rat liver sections revealed inimical cellular alterations caused by repeated exposure to Fijk. Study provides evidence that oral and repeated exposure to Fijk in rats raised the atherogenic index and potentiated oxidative stress as well as hepatic injury. PMID:25386188

  1. Lipid Profile and Oxidative Stress Markers in Wistar Rats following Oral and Repeated Exposure to Fijk Herbal Mixture.

    PubMed

    Adeyemi, Oluyomi Stephen; Orekoya, Bukola Temitope

    2014-01-01

    This study determined the effect of the oral and repeated administration of Fijk herbal mixture on rat biochemical and morphological parameters. Twenty-four Wistar rats were distributed into four groups of 6. Group A served as control and received oral administration of distilled water daily. The experimental groups B, C, and D were daily and orally exposed to Fijk herbal mixture at 15, 30, and 45 mg/kg, respectively. Treatments lasted for 21 days. The rats were sacrificed under mild diethyl ether anesthesia 24 hr after cessation of treatment. The blood and liver samples were collected and used for the biochemical and morphological analyses. Oral exposure to Fijk caused elevated levels of rat plasma ALT, AST, triglycerides, LDL, and MDA. In contrast, rat plasma HDL, GSH, and ALP levels were lowered by Fijk oral exposure. Also, the herbal remedy caused a dose-dependent elevation in the plasma atherogenic index. The histopathology examinations of rat liver sections revealed inimical cellular alterations caused by repeated exposure to Fijk. Study provides evidence that oral and repeated exposure to Fijk in rats raised the atherogenic index and potentiated oxidative stress as well as hepatic injury. PMID:25386188

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  4. Chemokines as Potential Markers in Pediatric Renal Diseases

    PubMed Central

    Simões e Silva, Ana Cristina; Pereira, André Barreto; Teixeira, Mauro Martins; Teixeira, Antônio Lúcio

    2014-01-01

    Glomerular diseases and obstructive uropathies are the two most frequent causes of chronic kidney disease (CKD) in children. Recently, biomarkers have become a focus of clinical research as potentially useful diagnostic tools in pediatric renal diseases. Among several putative biomarkers, chemokines emerge as promising molecules since they play relevant roles in the pathophysiology of pediatric renal diseases. The evaluation of these inflammatory mediators might help in the management of diverse renal diseases in children and the detection of patients at high risk to develop CKD. The aim of this paper is to revise general aspects of chemokines and the potential link between chemokines and the most common pediatric renal diseases by including experimental and clinical evidence. PMID:24692841

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

    NASA Astrophysics Data System (ADS)

    Yoshida, K.

    2016-03-01

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

  6. 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

    2015-01-01

    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

  7. Levels of biological markers of nitric oxide in serum of patients with squamous cell carcinoma of the oral cavity

    PubMed Central

    Ratajczak-Wrona, Wioletta; Jablonska, Ewa; Antonowicz, Bozena; Dziemianczyk, Dorota; Grabowska, Stanislawa Zyta

    2013-01-01

    The aim of the study was a determination of the levels of nitric oxide (NO) and its biological markers such as malonyldialdehyde (MDA) and nitrotyrosine in the serum of patients with squamous cell carcinoma (SCC) of the oral cavity and identification of the relationships between NO and those markers. These studies were performed on patients with SCC of the oral cavity before and after treatment. Griess reaction was used for the estimation of the total concentration of NO in serum. The nitrotyrosine level in serum was assessed with an enzyme-linked immunosorbent assay (ELISA) kit, and MDA level using a spectrophotometric assay. Higher concentrations of NO in blood serum were determined in patients with stage IV of the disease before treatment in comparison to the control group and patients with stages II and III of the disease. Moreover, higher concentrations of MDA and nitrotyrosine were determined in the serum of patients in all stages of the disease in comparison to healthy people. After treatment, lower concentrations of NO in the serum of patients with stage IV of the disease were observed in comparison to the amounts obtained prior to treatment. In addition, lower levels of nitrotyrosine in the serum of patients with all stages of the disease were recorded, whereas higher concentrations of MDA were determined in these patients in comparison to results obtained before treatment. The compounds formed with the contribution of NO, such as MDA and nitrotyrosine, may lead to cancer progression in patients with SCC of the oral cavity, and contribute to formation of resistance to therapy in these patients as well. Moreover, the lack of a relationship between concentrations of NO and MDA, and between NO and nitrotyrosine in serum suggests that the process of lipid peroxidation and nitration in patients with SCC does not just depend on NO. PMID:23970140

  8. Changes in bone turnover markers and menstrual function after short-term oral DHEA in young women with anorexia nervosa.

    PubMed

    Gordon, C M; Grace, E; Emans, S J; Goodman, E; Crawford, M H; Leboff, M S

    1999-01-01

    Bone loss is a serious consequence of anorexia nervosa (AN). Subnormal levels of serum dehydroepiandrosterone (DHEA) are seen in patients with AN and may be causally linked to their low bone density. We hypothesized that oral DHEA would decrease markers of bone resorption (urinary N-telopeptides [NTx]), and increase markers of bone formation (serum bone-specific alkaline phosphatase and osteocalcin [OC]). Fifteen young women (age 15-22 years) with AN were enrolled in a 3-month, randomized, double-blinded trial of 50, 100, or 200 mg of daily micronized DHEA. Blood and urinary levels of adrenal and gonadal steroids and bone turnover markers were measured. No adverse clinical side effects of DHEA were noted, and a 50 mg daily dose restored physiologic hormonal levels. At 3 months, NTx levels had decreased significantly in both the 50 mg (p = 0.018) and the 200 mg (p = 0.016) subgroups. OC levels simultaneously increased within treatment groups over time (p = 0.002). Eight out of 15 (53%) subjects had at least one menstrual cycle while on therapy. Short-term DHEA was well-tolerated and appears to normalize bone turnover in young women with AN. Resumption of menses in over half of subjects suggests that DHEA therapy may also lead to estradiol levels sufficient to stimulate the endometrium in this group of patients. PMID:9893076

  9. Circulating miRNAs as Potential Marker for Pulmonary Hypertension

    PubMed Central

    Wei, Chuanyu; Henderson, Heather; Spradley, Christopher; Li, Li; Kim, Il-Kwon; Kumar, Sandeep; Hong, Nayeon; Arroliga, Alejandro C.; Gupta, Sudhiranjan

    2013-01-01

    MircoRNAs (miRNAs) are small non-coding RNAs that govern the gene expression and, play significant role in the pathogenesis of heart failure. The detection of miRNAs in circulation of pulmonary hypertensive (PH) human subjects remains elusive. In the current study, we determined the pattern of miRNAs of mild-to-severe human PH subjects and, compared them with the control subjects by miRNA array. Blood was obtained using fluoroscopic and waveform guided catheterization from the distal (pulmonary artery) port of the catheter. A total 40 human subjects were included in the study and, the degree of PH was determined by mean pulmonary arterial pressure. Among several miRNAs in the array, we validated 14 miRNAs and, the data were consistent with the array profile. We identified several novel downregulated miRNAs (miR-451, miR-1246) and upregulated miRNAs (miR-23b, miR-130a and miR-191) in the circulation of PH subjects. Our study showed novel set of miRNAs which are dysregulated in PH and, are directly proportional to the degree of PH. These miRNAs may be considered as potential biomarker for early detection of PH. PMID:23717609

  10. Acne - a potential skin marker of internal disease.

    PubMed

    Pace, Joseph L

    2015-01-01

    Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in adult women. Hyperandrogenism is the crux of the pathogenesis of both acne and hirsutism, the most frequent clinical presentations of the syndrome. The chronic anovulation that may occur, often but not always associated with enlarged cystic ovaries, has long been recognized as an important feature of PCOS. In recent years major changes have occurred with regard to PCOS: Although management of the common cutaneous manifestations, mainly acne, hirsutism, alopecia, and acanthosis nigricans, remains strictly within the realm of daily dermatologic practice, the pendulum is shifting toward greater awareness of the longer-term systemic implications of PCOS, with emphasis on the unique opportunity and privileged position of the dermatologist to diagnose this potentially serious problem at an early stage, when effective long-term treatment can be instituted. Patients need to be advised that PCOS cannot be cured but can be controlled. Management should involve a multidisciplinary team with emphasis on lifestyle change, insulin sensitizing agents, androgen blockers, and attention to specific cutaneous manifestations. PMID:26321405

  11. 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

  12. Identifying Potential Markers of the Sun's Giant Convective Scale

    NASA Astrophysics Data System (ADS)

    McIntosh, Scott W.; Wang, Xin; Leamon, Robert J.; Scherrer, Philip H.

    2014-04-01

    Line-of-sight magnetograms from the Helioseismic and Magnetic Imager (HMI) of the Solar Dynamics Observatory (SDO) are analyzed using a diagnostic known as the magnetic range of influence (MRoI). The MRoI is a measure of the length over which a photospheric magnetogram is balanced and so its application gives the user a sense of the connective length scales in the outer solar atmosphere. The MRoI maps and histograms inferred from the SDO/HMI magnetograms primarily exhibit four scales: a scale of a few megameters that can be associated with granulation, a scale of a few tens of megameters that can be associated with super-granulation, a scale of many hundreds to thousands of megameters that can be associated with coronal holes and active regions, and a hitherto unnoticed scale that ranges from 100 to 250 Mm. We infer that this final scale is an imprint of the (rotationally driven) giant convective scale on photospheric magnetism. This scale appears in MRoI maps as well-defined, spatially distributed concentrations that we have dubbed "g-nodes." Furthermore, using coronal observations from the Atmospheric Imaging Assembly on SDO, we see that the vicinity of these g-nodes appears to be a preferred location for the formation of extreme-ultraviolet (and likely X-Ray) brightpoints. These observations and straightforward diagnostics offer the potential of a near real-time mapping of the Sun's largest convective scale, a scale that possibly reaches to the very bottom of the convective zone.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  16. Identification of methylation markers for the prediction of nodal metastasis in oral and oropharyngeal squamous cell carcinoma

    PubMed Central

    Melchers, LJ; Clausen, MJAM; Mastik, MF; Slagter-Menkema, L; van der Wal, JE; Wisman, GBA; Roodenburg, JLN; Schuuring, E

    2015-01-01

    Hypermethylation is an important mechanism for the dynamic regulation of gene expression, necessary for metastasizing tumour cells. Our aim is to identify methylation tumour markers that have a predictive value for the presence of regional lymph node metastases in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). Significantly differentially expressed genes were retrieved from four reported microarray expression profiles comparing pN0 and pN+ head-neck tumours, and one expression array identifying functionally hypermethylated genes. Additional metastasis-associated genes were included from the literature. Thus genes were selected that influence the development of nodal metastases and might be regulated by methylation. Methylation-specific PCR (MSP) primers were designed and tested on 8 head-neck squamous cell carcinoma cell lines and technically validated on 10 formalin-fixed paraffin-embedded (FFPE) OOSCC cases. Predictive value was assessed in a clinical series of 70 FFPE OOSCC with pathologically determined nodal status. Five out of 28 methylation markers (OCLN, CDKN2A, MGMT, MLH1 and DAPK1) were frequently differentially methylated in OOSCC. Of these, MGMT methylation was associated with pN0 status (P = 0.02) and with lower immunoexpression (P = 0.02). DAPK1 methylation was associated with pN+ status (P = 0.008) but did not associate with protein expression. In conclusion, out of 28 candidate genes, two (7%) showed a predictive value for the pN status. Both genes, DAPK1 and MGMT, have predictive value for nodal metastasis in a clinical group of OOSCC. Therefore DNA methylation markers are capable of contributing to diagnosis and treatment selection in OOSCC. To efficiently identify additional new methylation markers, genome-wide methods are needed. PMID:26213212

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

    PubMed

    Pazianas, Michael; Russell, R Graham G

    2011-12-01

    Bisphosphonates are the principal drugs prescribed for the prevention of osteoporotic fractures. They are bone specific but poorly absorbed. In oral formulations, almost 99% of the administered dose remains within the intestinal tract and reaches the small and large bowel. Although the nitrogen-containing bisphosphonates can irritate the distal esophageal/gastric mucosa, they improve drug-induced colitis in animal models and exhibit antitumor properties on intestinal cells in vitro. Several recent epidemiological studies provide evidence of a reduced risk of colorectal cancer in osteoporotic patients treated with oral bisphosphonates, notably alendronate. In this review, we will explore the possible mechanisms of action underlying these effects and raise the question of whether these agents might be used in the chemoprophylaxis against colorectal cancer. PMID:22360293

  18. Homeobox gene expression profile indicates HOXA5 as a candidate prognostic marker in oral squamous cell carcinoma

    PubMed Central

    RODINI, CAMILA OLIVEIRA; XAVIER, FLÁVIA CALÓ AQUINO; PAIVA, KATIÚCIA BATISTA SILVA; DE SOUZA SETÚBAL DESTRO, MARIA FERNANDA; MOYSES, RAQUEL AJUB; MICHALUARTE, PEDRO; CARVALHO, MARCOS BRASILINO; FUKUYAMA, ERICA ERINA; TAJARA, ELOIZA HELENA; OKAMOTO, OSWALDO KEITH; NUNES, FABIO DAUMAS

    2012-01-01

    The search for molecular markers to improve diagnosis, individualize treatment and predict behavior of tumors has been the focus of several studies. This study aimed to analyze homeobox gene expression profile in oral squamous cell carcinoma (OSCC) as well as to investigate whether some of these genes are relevant molecular markers of prognosis and/or tumor aggressiveness. Homeobox gene expression levels were assessed by microarrays and qRT-PCR in OSCC tissues and adjacent non-cancerous matched tissues (margin), as well as in OSCC cell lines. Analysis of microarray data revealed the expression of 147 homeobox genes, including one set of six at least 2-fold up-regulated, and another set of 34 at least 2-fold down-regulated homeobox genes in OSCC. After qRT-PCR assays, the three most up-regulated homeobox genes (HOXA5, HOXD10 and HOXD11) revealed higher and statistically significant expression levels in OSCC samples when compared to margins. Patients presenting lower expression of HOXA5 had poorer prognosis compared to those with higher expression (P=0.03). Additionally, the status of HOXA5, HOXD10 and HOXD11 expression levels in OSCC cell lines also showed a significant up-regulation when compared to normal oral keratinocytes. Results confirm the presence of three significantly upregulated (>4-fold) homeobox genes (HOXA5, HOXD10 and HOXD11) in OSCC that may play a significant role in the pathogenesis of these tumors. Moreover, since lower levels of HOXA5 predict poor prognosis, this gene may be a novel candidate for development of therapeutic strategies in OSCC. PMID:22227861

  19. Homeobox gene expression profile indicates HOXA5 as a candidate prognostic marker in oral squamous cell carcinoma.

    PubMed

    Rodini, Camila Oliveira; Xavier, Flávia Caló Aquino; Paiva, Katiúcia Batista Silva; De Souza Setúbal Destro, Maria Fernanda; Moyses, Raquel Ajub; Michaluarte, Pedro; Carvalho, Marcos Brasilino; Fukuyama, Erica Erina; Tajara, Eloiza Helena; Okamoto, Oswaldo Keith; Nunes, Fabio Daumas

    2012-04-01

    The search for molecular markers to improve diagnosis, individualize treatment and predict behavior of tumors has been the focus of several studies. This study aimed to analyze homeobox gene expression profile in oral squamous cell carcinoma (OSCC) as well as to investigate whether some of these genes are relevant molecular markers of prognosis and/or tumor aggressiveness. Homeobox gene expression levels were assessed by microarrays and qRT-PCR in OSCC tissues and adjacent non-cancerous matched tissues (margin), as well as in OSCC cell lines. Analysis of microarray data revealed the expression of 147 homeobox genes, including one set of six at least 2-fold up-regulated, and another set of 34 at least 2-fold down-regulated homeobox genes in OSCC. After qRT-PCR assays, the three most up-regulated homeobox genes (HOXA5, HOXD10 and HOXD11) revealed higher and statistically significant expression levels in OSCC samples when compared to margins. Patients presenting lower expression of HOXA5 had poorer prognosis compared to those with higher expression (P=0.03). Additionally, the status of HOXA5, HOXD10 and HOXD11 expression levels in OSCC cell lines also showed a significant up-regulation when compared to normal oral keratinocytes. Results confirm the presence of three significantly upregulated (>4-fold) homeobox genes (HOXA5, HOXD10 and HOXD11) in OSCC that may play a significant role in the pathogenesis of these tumors. Moreover, since lower levels of HOXA5 predict poor prognosis, this gene may be a novel candidate for development of therapeutic strategies in OSCC. PMID:22227861

  20. Identification of NbME MITE families: potential molecular markers in the microsporidia Nosema bombycis.

    PubMed

    Xu, Jinshan; Wang, Min; Zhang, Xiaoyan; Tang, Fahui; Pan, Guoqing; Zhou, Zeyang

    2010-01-01

    Six novel families of miniature inverted-repeat transposable elements (MITEs) were characterized in the microsporidia Nosema bombycis and were named NbMEs. The structural characteristics and the distribution of NbME copies in the N. bombycis genome were investigated, and it was found that portions of NbMEs are associated with gene sections. Potential molecular markers for various N. bombycis strains were identified in this study through utilization of the MITE-AFLP technique. Three distinct pathogenic isolates collected from different areas were distinguished, and polymorphisms were detected using the NbME5 marker, thereby establishing this NbME as a potential marker for studying isolate variation in N. bombycis. PMID:19861130

  1. Evaluation of natural killer cell (CD57) as a prognostic marker in oral squamous cell carcinoma: An immunohistochemistry study

    PubMed Central

    Agarwal, Rashmi; Chaudhary, Minal; Bohra, Shruti; Bajaj, Shree

    2016-01-01

    Objectives: Natural killer (NK) cells are important effector lymphocytes. NK cells are considered to represent innate immune system. NK cells target and kill aberrant cells such as virally infected and tumorigenic cells. The purpose of this study was to assess the expression of CD57 in oral squamous cell carcinoma (OSCC) and to correlate the expression of CD57 with 3 years survival in patients with OSCC. Materials and Methods: About 100 histopathologically diagnosed cases of OSCC of various grades were divided into two groups, i.e., Group I (dead patients) and Group II (live patients) from the archives of Department of Oral Pathology and Microbiology. CD57 was detected in these tissues by immunohistochemistry. Result: The results were analyzed using Spearman's correlation coefficient and students unpaired t-test. The mean CD57 labeling index in Group II was significantly higher than that found in Group I (P = 0.000). There was a significant correlation (P = 0.00) in the mean CD57 levels between Groups I and II and prognosis of patient. Conclusion: CD57 could be a good prognostic marker for OSCC patients. PMID:27601804

  2. Annexin A8 is a novel molecular marker for detecting lymph node metastasis in oral squamous cell carcinoma

    PubMed Central

    Goda, Hiroyuki; Iwamoto, Kazuki; Tokuzen, Norihiko; Hamakawa, Hiroyuki

    2016-01-01

    Cervical lymph node metastasis is an important prognostic factor in oral squamous cell carcinoma (OSCC), but its accurate assessment after sentinel node biopsy or neck dissection is often limited to the histopathological examination of only one or two sections. Previous our study showed the usefulness of the reverse transcription loop-mediated isothermal amplification (RT-LAMP) targeting keratin 19 (KRT19) mRNA for the genetic detection of lymph node metastasis, but the sensitivity was insufficient. Here, we have attempted to identify novel molecular markers for OSCC cells in lymph nodes. We performed microarray analysis to identify genes overexpressed in 7 metastatic lymph nodes from OSCC patients, compared to 1 normal lymph node and 5 salivary glands from non-cancer patients. We then used real-time quantitative RT-PCR (qRT-PCR) and RT-LAMP to compare the expression of these genes in newly resected metastatic and normal lymph nodes. Of 4 genes identified by microarray analysis, annexin A8 (ANXA8) and desmoglein 3 mRNA were detected by qRT-PCR in metastatic lymph nodes but not in normal lymph nodes. Furthermore, ANXA8 mRNA expression was detected in all KRT19-negative metastatic lymph nodes. Both KRT19 and ANXA8 mRNA may be useful markers for detecting lymph node metastases in OSCC patients. PMID:26700817

  3. X-linked markers in the Duchenne muscular dystrophy gene associated with oral clefts.

    PubMed

    Patel, Poorav J; Beaty, Terri H; Ruczinski, Ingo; Murray, Jeffrey C; Marazita, Mary L; Munger, Ronald G; Hetmanski, Jacqueline B; Wu, Tao; Murray, Tanda; Rose, Margaret; Redett, Richard J; Jin, Sheng C; Lie, Rolv T; Wu-Chou, Yah-Huei; Wang, Hong; Ye, Xiaoqian; Yeow, Vincent; Chong, Samuel; Jee, Sun H; Shi, Bing; Scott, Alan F

    2013-04-01

    As part of an international consortium, case-parent trios were collected for a genome-wide association study of isolated, non-syndromic oral clefts, including cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP). Non-syndromic oral clefts have a complex and heterogeneous etiology. Risk is influenced by genes and environmental factors, and differs markedly by gender. Family-based association tests (FBAT) were used on 14,486 single nucleotide polymorphisms (SNPs) spanning the X chromosome, stratified by type of cleft and racial group. Significant results, even after multiple-comparisons correction, were obtained for the Duchenne muscular dystrophy (DMD) gene, the largest single gene in the human genome, among CL/P (i.e., both CL and CLP combined) trios. When stratified into groups of European and Asian ancestry, stronger signals were obtained for Asian subjects. Although conventional sliding-window haplotype analysis showed no increase in significance, selected combinations of the 25 most significant SNPs in the DMD gene identified four SNPs together that attained genome-wide significance among Asian CL/P trios, raising the possibility of interaction between distant SNPs within the DMD gene. PMID:23489894

  4. ICAM1 Is a Potential Cancer Stem Cell Marker of Esophageal Squamous Cell Carcinoma

    PubMed Central

    Tsai, Sheng-Ta; Wang, Po-Jen; Liou, Nia-Jhen; Lin, Pei-Shan; Chen, Chung-Hsuan; Chang, Wei-Chao

    2015-01-01

    Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of esophageal cancer diagnosed in Asian countries, with its incidence on the rise. Cancer stem cell (CSC; also known as tumor-initiating cells, TIC) is inherently resistant to cytotoxic chemotherapy and radiation and associates with poor prognosis and therapy failure. Targeting therapy against cancer stem cell has emerged as a potential therapeutic approach to develop effective regimens. However, the suitable CSC marker of ESCC for identification and targeting is still limited. In this study, we screened the novel CSC membrane protein markers using two distinct stemness characteristics of cancer cell lines by a comparative approach. After the validation of RT-PCR, qPCR and western blot analyses, intercellular adhesion molecule 1 (ICAM1) was identified as a potential CSC marker of ESCC. ICAM1 promotes cancer cell migration, invasion as well as increasing mesenchymal marker expression and attenuating epithelial marker expression. In addition, ICAM1 contributes to CSC properties, including sphere formation, drug resistance, and tumorigenesis in mouse xenotransplantation model. Based on the analysis of ICAM1-regulated proteins, we speculated that ICAM1 regulates CSC properties partly through an ICAM1-PTTG1IP-p53-DNMT1 pathway. Moreover, we observed that ICAM1 and CD44 could have a compensation effect on maintaining the stemness characteristics of ESCC, suggesting that the combination of multi-targeting therapies should be under serious consideration to acquire a more potent therapeutic effect on CSC of ESCC. PMID:26571024

  5. Leptin receptor polymorphism Gln223Arg (rs1137101) in oral squamous cell carcinoma and potentially malignant oral lesions.

    PubMed

    Domingos, Patrícia Luciana Batista; Farias, Lucyana Conceição; Pereira, Camila Santos; das Graças Pena, Geórgia; Reis, Tatiana Carvalho; Silva, Rosângela Ramos Veloso; Fraga, Carlos Alberto de Carvalho; de Souza, Marcela Gonçalves; Soares, Mariana Batista; Jones, Kimberly Marie; Menezes, Elytania Veiga; Nobre, Sérgio Avelino Mota; Rodrigues Neto, João Felício; de Paula, Alfredo Maurício Batista; Velásquez-Meléndez, Jorge Gustavo; Sena Guimarães, André Luiz

    2014-01-01

    The purpose of this study was to assess the LEPR gene Gln223Arg polymorphism (rs1137101) in oral squamous cell carcinoma (OSCC) and in potentially malignant oral lesions (PMOL) in comparison to normal oral mucosa in a Brazilian population. Smokers (n = 89) were selected from a representative sample of 471 individuals from the general population of Montes Claros, Brazil. Participants were age and gender matched to patients with OSCC (n = 25) and oral epithelial dysplasia (n = 25). We investigated the LEPR Gln223Arg polymorphism (A>G; rs1137101) in these groups. Genotype variants were assessed by RFLP-PCR, using MspI (HPAII) restriction endonuclease. The institutional review board of the Universidade Estadual de Montes Claros approved the study (process number 2667/2011). Written informed consent for this study was obtained from all participants. The GG genotype (Arg223Arg) appears to be the more relevant polymorphic variant in OSCC. It occurred, approximately, twice as frequently in OSCC patients than in the general population. In contrast, the A allele in its homozygosis form (Gln223Gln) is significantly associated with the development of PMOL; 80% of the samples from the PMOL group exhibit AA genotype. Our findings suggest new insights regarding LEPR gene variations in the development of OSCC and PMOL. PMID:26034683

  6. GhSEM-1 marker potentially associated with regeneration ability in cotton.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A marker protein for embryogenic potential could be useful in determining if target tissue for Agrobacterium tumefaciens or microprojectile bombardment has the ability to regenerate plants. Certain varieties of cotton, especially Coker 312, are known to form somatic embryos readily, while others are...

  7. 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.

  8. An efficient method to find potentially universal population genetic markers, applied to metazoans

    PubMed Central

    2010-01-01

    Background Despite the impressive growth of sequence databases, the limited availability of nuclear markers that are sufficiently polymorphic for population genetics and phylogeography and applicable across various phyla restricts many potential studies, particularly in non-model organisms. Numerous introns have invariant positions among kingdoms, providing a potential source for such markers. Unfortunately, most of the few known EPIC (Exon Primed Intron Crossing) loci are restricted to vertebrates or belong to multigenic families. Results In order to develop markers with broad applicability, we designed a bioinformatic approach aimed at avoiding multigenic families while identifying intron positions conserved across metazoan phyla. We developed a program facilitating the identification of EPIC loci which allowed slight variation in intron position. From the Homolens databases we selected 29 gene families which contained 52 promising introns for which we designed 93 primer pairs. PCR tests were performed on several ascidians, echinoderms, bivalves and cnidarians. On average, 24 different introns per genus were amplified in bilaterians. Remarkably, five of the introns successfully amplified in all of the metazoan genera tested (a dozen genera, including cnidarians). The influence of several factors on amplification success was investigated. Success rate was not related to the phylogenetic relatedness of a taxon to the groups that most influenced primer design, showing that these EPIC markers are extremely conserved in animals. Conclusions Our new method now makes it possible to (i) rapidly isolate a set of EPIC markers for any phylum, even outside the animal kingdom, and thus, (ii) compare genetic diversity at potentially homologous polymorphic loci between divergent taxa. PMID:20836842

  9. 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 μg/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 μg/mL. Porphyromonas gingivalis, an anaerobic, gram-negative pathogen and the bacterium most associated with chronic periodontitis, demonstrated the lowest sensitivity to allicin (2,400 μg/mL). Gel zymography and the synthetic chromogenic substrate N(α)-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 μg/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

  10. Plasma protoporphyrin IX following administration of 5-aminolevulinic acid as a potential tumor marker

    PubMed Central

    OTA, URARA; FUKUHARA, HIDEO; ISHIZUKA, MASAHIRO; ABE, FUMINORI; KAWADA, CHIAKI; TAMURA, KENJI; TANAKA, TOHRU; INOUE, KEIJI; OGURA, SHUN-ICHIRO; SHUIN, TARO

    2015-01-01

    Exogenously administered 5-aminolevulinic acid (ALA) is metabolized to protoporphyrin IX (PpIX), which specifically accumulates in cancer cells and emits red fluorescence by blue light irradiation. These phenomena are applied for the intraoperative diagnosis of cancer. Based on the fact that accumulated PpIX in cancer cells is exported extracellularly via the ATP-binding cassette transporter G2, we hypothesized that the measurement of plasma PpIX concentrations could be applied as a tumor marker for cancer screening. In the present study, the use of plasma samples from bladder cancer patients were evaluated as a tumor marker. ALA, 1.0 g, was orally administered to bladder cancer patients and healthy adults. The plasma concentration of PpIX was measured using a high-performance liquid chromatography system. The plasma PpIX concentration following ALA administration was significantly higher in bladder cancer patients than that in the healthy adults, suggesting the effectiveness of plasma PpIX analysis following ALA administration for cancer screening. Additionally, 4 h after ALA administration, plasma PpIX showed high sensitivity (94.4%) and high specificity (80.0%). PMID:26171183

  11. A strategy to reveal potential glycan markers from serum glycoproteins associated with breast cancer progression.

    PubMed

    Abd Hamid, Umi M; Royle, Louise; Saldova, Radka; Radcliffe, Catherine M; Harvey, David J; Storr, Sarah J; Pardo, Maria; Antrobus, Robin; Chapman, Caroline J; Zitzmann, Nicole; Robertson, John F; Dwek, Raymond A; Rudd, Pauline M

    2008-12-01

    Aberrant glycosylation on glycoproteins that are either presented on the surface or secreted by cancer cells is a potential source of disease biomarkers and provides insights into disease pathogenesis. N-Glycans of the total serum glycoproteins from advanced breast cancer patients and healthy individuals were sequenced by HPLC with fluorescence detection coupled with exoglycosidase digestions and mass spectrometry. We observed a significant increase in a trisialylated triantennary glycan containing alpha1,3-linked fucose which forms part of the sialyl Lewis x epitope. Following digestion of the total glycan pool with a combination of sialidase and beta-galactosidase, we segregated and quantified a digestion product, a monogalactosylated triantennary structure containing alpha1,3-linked fucose. We compared breast cancer patients and controls and detected a 2-fold increase in this glycan marker in patients. In 10 patients monitored longitudinally, we showed a positive correlation between this glycan marker and disease progression and also demonstrated its potential as a better indicator of metastasis compared to the currently used biomarkers, CA 15-3 and carcinoembryonic antigen (CEA). A pilot glycoproteomic study of advanced breast cancer serum highlighted acute-phase proteins alpha1-acid glycoprotein, alpha1-antichymotrypsin, and haptoglobin beta-chain as contributors to the increase in the glycan marker which, when quantified from each of these proteins, marked the onset of metastasis in advance of the CA 15-3 marker. These preliminary findings suggest that specific glycans and glycoforms of proteins may be candidates for improved markers in the monitoring of breast cancer progression. PMID:18818422

  12. Sperm midpiece apoptotic markers: impact on fertilizing potential in in vitro fertilization and intracytoplasmic sperm injection.

    PubMed

    Talarczyk-Desole, Joanna; Kotwicka, Małgorzata; Jendraszak, Magdalena; Pawelczyk, Leszek; Murawski, Marek; Jędrzejczak, Piotr

    2016-04-01

    The aim of this study was to investigate the relationship between apoptotic markers present in human spermatozoa, namely phosphatidylserine translocation (PST) from the inner to the outer layer of the cytomembrane and the active form of caspase-3 (c3) versus the fertilizing potential of male gametes in conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) models. A total of 116 male patients treated with their partners for infertility underwent basic semen analysis and an assessment of the presence of PST and the active c3 in sperm using flow cytometry. Forty patients underwent IVF, group A, while 76 patients underwent ICSI, group B. The fertilizing potential of the gametes was measured as the percentage of oocytes with pronuclei present after either procedure. PST and active c3 were identified in vital gametes, mainly in the midpiece area. Concentration, motility, morphology, and viability of spermatozoa strongly negatively correlated with both markers. In group A, a negative correlation between both markers and the success rate of conventional IVF was observed (r = -0.4, p = 0.04 for PST; r = -0.4, p = 0.02 for active c3, respectively). In group B, the success rate of ICSI did not correlate with either marker (r = -0.2, p = 0.85 for PST and r = 0.1, p = 0.51 for active c3). The two apoptotic markers localized in the sperm midpiece area may affect their function not only by decreasing basic andrologic parameters but also by reducing the probability of conception. Therefore, analysis of PST and active c3 in the sperm of patients undergoing infertility treatment should be recommended. PMID:26791536

  13. 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

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

    PubMed

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

    2009-07-01

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

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

    PubMed Central

    Taichman, L. Susan; Havens, Aaron M.

    2012-01-01

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

  16. Comprehensive urinary metabolomic profiling and identification of potential noninvasive marker for idiopathic Parkinson’s disease

    PubMed Central

    Luan, Hemi; Liu, Liang-Feng; Tang, Zhi; Zhang, Manwen; Chua, Ka-Kit; Song, Ju-Xian; Mok, Vincent C.T.; Li, Min; Cai, Zongwei

    2015-01-01

    Urine metabolic phenotyping has been associated with the development of Parkinson’s disease (PD). However, few studies using a comprehensive metabolomics approach have investigated the correlation between changes in the urinary markers and the progression of clinical symptoms in PD. A comprehensive metabolomic study with robust quality control procedures was performed using gas chromatography - mass spectrometry (GC - MS) and liquid chromatography - mass spectrometry (LC - MS) to characterize the urinary metabolic phenotypes of idiopathic PD patients at three stages (early, middle and advanced) and normal control subjects, with the aim of discovering potential urinary metabolite markers for the diagnosis of idiopathic PD. Both GC-MS and LC-MS metabolic profiles of idiopathic PD patients differed significantly from those of normal control subjects. 18 differentially expressed metabolites were identified as constituting a unique metabolic marker associated with the progression of idiopathic PD. Related metabolic pathway variations were observed in branched chain amino acid metabolism, glycine derivation, steroid hormone biosynthesis, tryptophan metabolism, and phenylalanine metabolism. Comprehensive, successive metabolomic profiling revealed changes in the urinary markers associated with progression of idiopathic PD. This profiling relies on noninvasive sampling, and is complementary to existing clinical modalities. PMID:26365159

  17. Cystatin C: a new renal marker and its potential use in small animal medicine.

    PubMed

    Ghys, L; Paepe, D; Smets, P; Lefebvre, H; Delanghe, J; Daminet, S

    2014-01-01

    The occurrence of chronic kidney disease is underestimated in both human and veterinary medicine. Glomerular filtration rate (GFR) is considered the gold standard for evaluating kidney function. However, GFR assessment is time-consuming and labor-intensive and therefore not routinely used in practice. The commonly used indirect GFR markers, serum creatinine (sCr) and urea, are not sufficiently sensitive or specific to detect early renal dysfunction. Serum cystatin C (sCysC), a proteinase inhibitor, has most of the properties required for an endogenous GFR marker. In human medicine, numerous studies have evaluated its potential use as a GFR marker in several populations. In veterinary medicine, this marker is gaining interest. The measurement is easy, which makes it an interesting parameter for clinical use. This review summarizes current knowledge about cystatin C (CysC) in humans, dogs, and cats, including its history, assays, relationship with GFR, and biological and clinical variations in both human and veterinary medicine. PMID:24814357

  18. A comparison of the management of potentially malignant oral mucosal lesions by oral medicine practitioners and oral & maxillofacial surgeons in the UK.

    PubMed

    Marley, J J; Linden, G J; Cowan, C G; Lamey, P J; Johnson, N W; Warnakulasuriya, K A; Scully, C

    1998-11-01

    This study describes the results of a survey undertaken to assess the management of potentially malignant oral mucosal lesions by oral medicine practitioners and compares their approach with that of oral & maxillofacial surgeons that we have previously described. Significant differences were noted between the two groups in the use of photography to document the lesions and in the use of certain special investigations, which included measurement of serum iron, serum ferritin, serum Vit B12, red cell folate and candidal isolation. The groups also varied in the perceived importance of the age of the patient and anatomical site of the lesion when deciding on the need for further biopsy. There was also significant variation in the use of certain treatment modalities, including excising non-dysplastic and severely dysplastic/carcinoma in-situ lesions and eliminating trauma when treating mild/moderately dysplastic and severely dysplastic/carcinoma in-situ lesions. Significant differences in the frequency and duration of follow-up were noted for non-dysplastic lesions. Finally, the two groups differed significantly when asked to rank the perceived importance of certain factors (the histopathology of the most recent biopsy and the anatomical site of the lesion) when deciding the need to follow-up. Possible reasons for the variation are discussed. PMID:9831962

  19. Potentiation of oral anticoagulation and hemarthrosis associated with nabumetone.

    PubMed

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

    2000-02-01

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

  20. Effect of orally administered L. fermentum NCIMB 5221 on markers of metabolic syndrome: an in vivo analysis using ZDF rats.

    PubMed

    Tomaro-Duchesneau, Catherine; Saha, Shyamali; Malhotra, Meenakshi; Jones, Mitchell L; Labbé, Alain; Rodes, Laetitia; Kahouli, Imen; Prakash, Satya

    2014-01-01

    Metabolic syndrome, encompassing type 2 diabetes mellitus and cardiovascular disease, is a growing health concern of industrialized countries. Ferulic acid (FA) is a phenolic acid found in foods normally consumed by humans that has demonstrated antioxidant activity, cholesterol-lowering capabilities, and anti-tumorigenic properties. Select probiotic bacteria, including Lactobacillus fermentum NCIMB 5221, produce FA due to intrinsic ferulic acid esterase activity. The aim of the present research was to investigate a FA-producing probiotic, L. fermentum NCIMB 5221, as a biotherapeutic for metabolic syndrome. The probiotic formulation was administered daily for 8 weeks to Zucker diabetic fatty (ZDF) rats, a model of hyperlipidemia and hyperglycemia. Results show that the probiotic formulation reduced fasting insulin levels and insulin resistance, significantly reduced serum triglycerides (p = 0.016), lowered serum low-density lipoprotein cholesterol levels (p = 0.008), and significantly reduced the atherogenic (p = 0.016) and atherosclerosis (p = 0.012) index as compared to the control animals. In addition, the probiotic formulation significantly increased high-density lipoprotein cholesterol levels (p = 0.041) as compared to the control animals. This research indicates that administration of the FA-producing L. fermentum NCIMB 5221 has the potential to reduce insulin resistance, hyperinsulinemia, hypercholesterolemia, and other markers involved in the pathogenesis of metabolic syndrome. Further studies are required to investigate the human clinical potential of the probiotic formulation in affecting the markers and pathogenesis of metabolic syndrome. PMID:24121931

  1. Molecular Markers of Diabetic Retinopathy: Potential Screening Tool of the Future?

    PubMed Central

    Pusparajah, Priyia; Lee, Learn-Han; Abdul Kadir, Khalid

    2016-01-01

    Diabetic retinopathy (DR) is among the leading causes of new onset blindness in adults. Effective treatment may delay the onset and progression of this disease provided it is diagnosed early. At present retinopathy can only be diagnosed via formal examination of the eye by a trained specialist, which limits the population that can be effectively screened. An easily accessible, reliable screening biomarker of diabetic retinopathy would be of tremendous benefit in detecting the population in need of further assessment and treatment. This review highlights specific biomarkers that show promise as screening markers to detect early diabetic retinopathy or even to detect patients at increased risk of DR at the time of diagnosis of diabetes. The pathobiology of DR is complex and multifactorial giving rise to a wide array of potential biomarkers. This review provides an overview of these pathways and looks at older markers such as advanced glycation end products (AGEs), inflammatory markers, vascular endothelial growth factor (VEGF) as well as other newer proteins with a role in the pathogenesis of DR including neuroprotective factors such as brain derived neurotrophic factor (BDNF) and Pigment Epithelium Derived Factor (PEDF); SA100A12, pentraxin 3, brain natriuretic peptide, apelin 3, and chemerin as well as various metabolites such as lipoprotein A, folate, and homocysteine. We also consider the possible role of proteins identified through proteomics work whose levels are altered in the sera of patients with DR as screening markers though their role in pathophysiology remains to be characterized. The role of microRNA as a promising new screening marker is also discussed. PMID:27313539

  2. Chromogranin A - unspecific neuroendocrine marker. Clinical utility and potential diagnostic pitfalls.

    PubMed

    Gut, Paweł; Czarnywojtek, Agata; Fischbach, Jakub; Bączyk, Maciej; Ziemnicka, Katarzyna; Wrotkowska, Elżbieta; Gryczyńska, Maria; Ruchała, Marek

    2016-02-01

    Chromogranin A, despite a number of limitations, is still the most valuable marker of neuroendocrine tumors (NETs). Granins belong to the family of acidic proteins that constitute a major component of secretory granules of various endocrine and neuroendocrine cells, which are components of both the classical endocrine glands and the diffuse neuroendocrine system. These cells are a potential source of transformation into neuroendocrine tumors. The awareness of potential causes influencing the false results of its concentrations simplifies diagnosis and treatment. One of the disadvantages of this marker is its non-specificity and the existence of a number of pathological processes leading to an increase in its concentration, which often results in confusion and diagnostic difficulties. The molecular structure is characterized by a number of sites susceptible to the proteolytic activity of enzymes, resulting in the formation of a number of biologically active peptides. Presumably they act as precursors of active proteins. Chromogranin expression correlates with the amount of secretory vesicles in neuroendocrine cells. The peptide chain during biochemical changes becomes a precursor of biologically active proteins with a wide range of activities. There are a number of commercially available kits for the determination of chromogranin A, which differ in methodology. We present the evaluation of chromogranin A as a marker of neuroendocrine tumors in clinical practice and the possible factors that may affect the outcome of its concentration. PMID:26925113

  3. Musashi1 as a potential therapeutic target and diagnostic marker for lung cancer.

    PubMed

    Wang, Xiao-Yang; Yu, Huina; Linnoila, R Ilona; Li, Laodong; Li, Dangyu; Mo, Biwen; Okano, Hideyuki; Penalva, Luiz O F; Glazer, Robert I

    2013-05-01

    Lung cancer remains one of the leading causes of cancer-related deaths worldwide with a 5-year survival rate of less than 20%. One approach to improving survival is the identification of biomarkers to detect early stage disease. In this study, we investigated the potential of the stem cell and progenitor cell marker, Musashi1 (Msi1), as a diagnostic marker and potential therapeutic target for lung cancer. Functional studies in A549 bronchioalveolar carcinoma and NCI-H520 squamous cell carcinoma cells revealed that Msi1 was enriched in spheroid cultures of tumor cells and in the CD133+ cell population. Downregulation of Msi1 by lentivirus-mediated expression of an Msi1 shRNA reduced spheroid colony proliferation. Growth inhibition was associated with reduced nuclear localization of β-catenin and inhibition of the processing of intracellular Notch. In primary lung cancer, Msi1 protein expression was elevated in 86% of 202 tissue microarray specimens, and Msi1 mRNA was increased in 80% of 118 bronchoscopic biopsies, including metastatic disease, but was rarely detected in adjacent normal lung tissue and in non-malignant diseased tissue. Msi1 was expressed in a diffuse pattern in most tumor subtypes, except in squamous cell carcinomas, where it appeared in a focal pattern in 50% of specimens. Thus, Msi1 is a sensitive and specific diagnostic marker for all lung cancer subtypes. PMID:23715514

  4. Musashi1 as a potential therapeutic target and diagnostic marker for lung cancer

    PubMed Central

    Linnoila, R. Ilona; Li, Laodong; Li, Dangyu; Mo, Biwen; Okano, Hideyuki; Penalva, Luiz O. F.; Glazer, Robert I.

    2013-01-01

    Lung cancer remains one of the leading causes of cancer-related deaths worldwide with a 5-year survival rate of less than 20%. One approach to improving survival is the identification of biomarkers to detect early stage disease. In this study, we investigated the potential of the stem cell and progenitor cell marker, Musashi1 (Msi1), as a diagnostic marker and potential therapeutic target for lung cancer. Functional studies in A549 bronchioalveolar carcinoma and NCI-H520 squamous cell carcinoma cells revealed that Msi1 was enriched in spheroid cultures of tumor cells and in the CD133+ cell population. Downregulation of Msi1 by lentivirus-mediated expression of an Msi1 shRNA reduced spheroid colony proliferation. Growth inhibition was associated with reduced nuclear localization of β-catenin and inhibition of the processing of intracellular Notch. In primary lung cancer, Msi1 protein expression was elevated in 86% of 202 tissue microarray specimens, and Msi1 mRNA was increased in 80% of 118 bronchoscopic biopsies, including metastatic disease, but was rarely detected in adjacent normal lung tissue and in non-malignant diseased tissue. Msi1 was expressed in a diffuse pattern in most tumor subtypes, except in squamous cell carcinomas, where it appeared in a focal pattern in 50% of specimens. Thus, Msi1 is a sensitive and specific diagnostic marker for all lung cancer subtypes. PMID:23715514

  5. Chromogranin A – unspecific neuroendocrine marker. Clinical utility and potential diagnostic pitfalls

    PubMed Central

    Czarnywojtek, Agata; Fischbach, Jakub; Bączyk, Maciej; Ziemnicka, Katarzyna; Wrotkowska, Elżbieta; Gryczyńska, Maria; Ruchała, Marek

    2016-01-01

    Chromogranin A, despite a number of limitations, is still the most valuable marker of neuroendocrine tumors (NETs). Granins belong to the family of acidic proteins that constitute a major component of secretory granules of various endocrine and neuroendocrine cells, which are components of both the classical endocrine glands and the diffuse neuroendocrine system. These cells are a potential source of transformation into neuroendocrine tumors. The awareness of potential causes influencing the false results of its concentrations simplifies diagnosis and treatment. One of the disadvantages of this marker is its non-specificity and the existence of a number of pathological processes leading to an increase in its concentration, which often results in confusion and diagnostic difficulties. The molecular structure is characterized by a number of sites susceptible to the proteolytic activity of enzymes, resulting in the formation of a number of biologically active peptides. Presumably they act as precursors of active proteins. Chromogranin expression correlates with the amount of secretory vesicles in neuroendocrine cells. The peptide chain during biochemical changes becomes a precursor of biologically active proteins with a wide range of activities. There are a number of commercially available kits for the determination of chromogranin A, which differ in methodology. We present the evaluation of chromogranin A as a marker of neuroendocrine tumors in clinical practice and the possible factors that may affect the outcome of its concentration. PMID:26925113

  6. Prevalence of potential drug–drug interactions in cancer patients treated with oral anticancer drugs

    PubMed Central

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

    2013-01-01

    Background: Potential drug–drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment. Methods: A search was conducted in a computer-based medication prescription system for dispensing oral anticancer drugs to outpatients in three Dutch centres. Potential drug–drug interactions were identified using electronic (Drug Interaction Fact software) and manual screening methods (peer-reviewed reports). Results: In the 898 patients included in the study, 1359 PDDIs were identified in 426 patients (46%, 95% confidence interval (CI)=42–50%). In 143 patients (16%), a major PDDI was identified. The drug classes most frequently involved in a major PDDI were coumarins and opioids. The majority of cases concerned central nervous system interactions, PDDIs that can cause gastrointestinal toxicity and prolongation of QT intervals. In multivariate analysis, concomitant use of more drugs (odds ratio (OR)=1.66, 95% CI=1.54–1.78, P<0001) and genito-urinary cancer (OR=0.25, 95% CI=0.12–0.52, P<0001) were risk factors. Conclusion: Potential drug–drug interactions are very common among cancer patients on oral cancer therapy. Physicians and pharmacists should be more aware of these potential interactions. PMID:23412102

  7. 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. PMID:26942144

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

    PubMed Central

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

    Lwin, Soe Marlar

    2016-01-01

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

  10. Folate Receptor Alpha, Mesothelin and Megakaryocyte Potentiating Factor as Potential Serum Markers of Chronic Kidney Disease

    PubMed Central

    Somers, Elizabeth B; O’Shannessy, Daniel J

    2014-01-01

    Renal disease is the eighth leading cause of death in the United States. Early diagnosis is usually based on the detection of proteinuria or elevated serum creatinine, a relatively poor biomarker that does not accurately predict renal disease progression. As a result, more predictive biomarkers of renal function are sought. We present preliminary data on three protein biomarkers, folate receptor alpha (FRA), mesothelin (MSLN), and megakaryocyte potentiating factor (MPF), currently being pursued for applications in oncology diagnostics, and evaluate serum and urine levels in subjects with renal disease. Compared to healthy subjects, a significant (P < 0.0001) increase in all three biomarkers in both serum and urine of subjects with renal disease was demonstrated. Further, serum levels of these three protein biomarkers increased with increasing stage of disease suggesting their potential value in predicting progression in subjects with renal disease and raising caution in interpretation of data in oncology applications. PMID:24932099

  11. E-cadherin in non-tumor epithelium adjacent to oral cancer as risk marker for the development of multiple tumors.

    PubMed

    González-Moles, M A; Bravo, M; Ruiz-Avila, I; Gil-Montoya, J A; Acebal, F; Esteban, F

    2013-03-01

    Our aim was to find out whether the loss of E-cadherin is a risk factor for the development of multiple tumours in the oral cavity and whether it could serve as a diagnostic marker for oral premalignant fields. We studied 77 oral squamous cell carcinomas (SCC) with associated non-tumour epithelia from 61 patients. Immunohistochemical studies (antibody NHC-38) were used to investigate E-cadherin expression, which was completely lost in basal (48% of cases) and parabasal (43%) layers of non-tumour epithelia close to the tumour and in basal (47%) and parabasal (38%) layers of non-tumour epithelia distant from the tumour. In multiple tumours E-cadherin expression was significantly lower than in single tumours in the basal, parabasal layers, and the middle third of close (p=0.002, <0.001, <0.001) and distant (p=0.041, p<0.001, p=0.005) non-tumour epithelia, respectively. Downregulation of E-cadherin may be valuable as a risk marker for the development of multiple tumours in the oral cavity and for the diagnosis of premalignant fields. PMID:22658605

  12. The potential utility of telomere-related markers for cancer diagnosis

    PubMed Central

    Heaphy, Christopher M; Meeker, Alan K

    2011-01-01

    Abstract The role telomeres and telomerase play in the initiation and progression of human cancers has been extensively evaluated. Telomeres are nucleoprotein complexes comprising the hexanucleotide DNA repeat sequence, TTAGGG and numerous telomere-associated proteins, including the six member Shelterin complex. The main function of the telomere is to stabilize the ends of the chromosomes. However, through multiple mechanisms, telomeres can become dysfunctional, which may drive genomic instability leading to the development of cancer. The majority of human cancers maintain, or actively lengthen, telomeres through up-regulation of the reverse transcriptase telomerase. Because there are significant differences in telomere length and telomerase activity between malignant and non-malignant tissues, many investigations have assessed the potential to utilize these molecular markers for cancer diagnosis. Here, we critically evaluate whether measurements of telomere lengths and telomerase levels may be clinically utilized as diagnostic markers in solid tumours, with emphasis on breast and prostate cancer as representative examples. Future directions focusing on the direct detection of dysfunctional telomeres are explored. New markers for telomere dysfunction may eventually prove clinically useful. PMID:21352473

  13. ABCG2 is a potential marker of tumor-initiating cells in breast cancer.

    PubMed

    Sicchieri, Renata Danielle; da Silveira, Willian Abraham; Mandarano, Larissa Raquel Mouro; de Oliveira, Tatiane Mendes Gonçalves; Carrara, Hélio Humberto Angotti; Muglia, Valdair Francisco; de Andrade, Jurandyr Moreira; Tiezzi, Daniel Guimarães

    2015-12-01

    The existence of tumor-initiating cells (TICs) within solid tumors has been hypothesized to explain tumor heterogeneity and resistance to cancer therapy. In breast cancer, the expression of CD44 and CD24 and the activity of aldehyde dehydrogenase 1 (ALDH1) can be used to selectively isolate a cell population enriched in TICs. However, the ideal marker to identify TICs has not been established. The aim of this study was to evaluate the expression of novel potential markers for TIC in breast carcinoma. We prospectively analyzed the expression of CD44, CD24, ABCG2, and CXCR4, and the activity of ALDH1 by using flow cytometry in 48 invasive ductal carcinomas from locally advanced and metastatic breast cancer patients who were administered primary chemotherapy. A mammosphere assay was employed in 30 samples. The relationship among flow cytometric analyses, ABCG2 gene expression, and clinical and pathological responses to therapy was analyzed. The GSE32646 database was analyzed in silico to identify genes associated with tumors with low and high ABCG2 expression. We observed that the presence of ABCG2(+) cells within the primary tumor was the only marker to predict the formation of mammospheres in vitro (R (2) = 0.15, p = 0.029). Quantitative polymerase chain reaction (qPCR) revealed a positive correlation between ABCG2 expression and the presence of ABCG2(+) cells within the primary tumor. The expression of ABCG2 was predictive of the response to neoadjuvant chemotherapy in our experiments and in the GSE32646 dataset (p = 0.04 and p = 0.002, respectively). The in silico analysis demonstrated that ABCG2(Up) breast cancer samples have a slower cell cycle and a higher expression of membrane proteins but a greater potential for chromosomal instability, metastasis, immune evasion, and resistance to hypoxia. Such genetic characteristics are compatible with highly aggressive and resistant tumors. Our results support the hypothesis that the presence of ABCG2

  14. Sirtuin-3 (SIRT3), a Novel Potential Therapeutic Target for Oral Cancer

    PubMed Central

    Alhazzazi, Turki Y; Kamarajan, Pachiyappan; Joo, Nam; Huang, Jing-Yi; Verdin, Eric; D'Silva, Nisha J; Kapila, Yvonne L

    2011-01-01

    BACKGROUND Several sirtuin family members (SIRT1-7), which are evolutionarily conserved NAD-dependent deacetylases, play an important role in carcinogenesis. However, their role in oral cancer has not yet been investigated. Therefore, the objective of this study was to investigate whether sirtuins play a role in oral cancer carcinogenesis. METHODS The expression levels of all sirtuins in several oral squamous cell carcinoma (OSCC) cell lines were compared with normal human oral keratinocytes and observed that SIRT3 was highly expressed. Therefore, tissue microarrays were used to evaluate the clinical relevance of this overexpression. SIRT3 down-regulation in OSCC cell proliferation and survival was investigated and analyzed by using cell-proliferation and cell-viability assays. Ionizing radiation and cisplatin were used to investigate whether SIRT3 down-regulation could increase the sensitivity of OSCC to both treatments. To further assess the in vivo role of SIRT3 in OSCC carcinogenesis, a floor-of-mouth oral cancer murine model was used to study the effect of SIRT3 down-regulation on OSCC tumor growth in immunodeficient mice. RESULTS The current results demonstrated for the first time that SIRT3 is overexpressed in OSCC in vitro and in vivo compared with other sirtuins. Down-regulation of SIRT3 inhibited OSCC cell growth and proliferation and increased OSCC cell sensitivity to radiation and cisplatin treatments in vitro. SIRT3 down-regulation also reduced tumor burden in vivo. CONCLUSIONS The current investigation revealed a novel role for SIRT3 in oral cancer carcinogenesis as a promoter of cell proliferation and survival, thus implicating SIRT3 as a new potential therapeutic target to treat oral cancer. Cancer 2011. © 2010 American Cancer Society. PMID:21472714

  15. Ameliorative potential of gingerol: Promising modulation of inflammatory factors and lipid marker enzymes expressions in HFD induced obesity in rats.

    PubMed

    Brahma Naidu, Parim; Uddandrao, V V Sathibabu; Ravindar Naik, Ramavat; Suresh, Pothani; Meriga, Balaji; Begum, Mustapha Shabana; Pandiyan, Rajesh; Saravanan, Ganapathy

    2016-01-01

    Obesity, generally linked to hyperlipidemia, has been occurring of late with distressing alarm and has now become a global phenomenon casting a huge economic burden on the health care system of countries around the world. The present study investigated the effects of gingerol over 30 days on the changes in HFD-induced obese rats in marker enzymes of lipid metabolism such as fatty-acid synthase (FAS), Acetyl CoA Carboxylase (ACC), Carnitine Palmitoyl Transferase-1(CPT-1), HMG co-A Reductase (HMGR), Lecithin Choline Acyl Transferase (LCAT) and Lipoprotein Lipase (LPL) and inflammatory markers (TNF-α and IL-6). The rats were treated orally with gingerol (75 mg kg(-1)) once daily for 30 days with a lorcaserin-treated group (10 mg kg(-1)) included for comparison. Changes in body weight, glucose, insulin resistance and expressions of lipid marker enzymes and inflammatory markers in tissues were observed in experimental rats. The administration of gingerol resulted in a significant reduction in body weight gain, glucose and insulin levels, and insulin resistance, which altered the activity, expressions of lipid marker enzymes and inflammatory markers. It showed that gingerol had significantly altered these parameters when compared with HFD control rats. This study confirms that gingerol prevents HFD-induced hyperlipidemia by modulating the expression of enzymes important to cholesterol metabolism. PMID:26493465

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2005-01-01

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

  18. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-03-15

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

  1. Enhanced gastric retention of solid resin beads as a marker for emetic potential of agents in rats.

    PubMed

    Ando, Kentaro; Takagi, Kan; Tsubone, Hirokazu

    2012-01-01

    Whereas nausea and emesis are burdensome side effects that lead to poor treatment compliance especially in chemotherapy, it is difficult to predict the emetic potential of agents in rats and mice because rodents do not vomit. We examined the effect of emetics on gastric retention and role of serotonin (5-hydroxytryptamine, 5-HT)3 receptor in chemotherapeutic-induced enhancement of gastric retention in rats. The gastric retention of solid material was determined using resin beads, which were suitable to beads made with metals or glasses in size, hardness and weight. Each rat was orally given distilled water (0.5 ml/rat) containing 40 resin beads via a plastic feeding tube. The stomach was removed at 1 hr post-dose and cut along the greater curvature under carbon dioxide anesthesia. Beads were given immediately after administration of the drugs except with cisplatin, when there was a 1 hr delay. Cancer chemotherapeutics including cisplatin(0.1-3 mg/kg i.v.) and doxorubicin(0.3-10 mg/kg i.v.) and a nauseant, copper sulfate(1-30 mg/kg p.o.) enhanced gastric retention of beads. Ondansetron, a 5-HT3 receptor antagonist, dose-dependently antagonized the enhanced gastric retention by cisplatin and doxorubicin. The copper sulfate-induced enhancement was also reversed by ondansetron. Our results suggest that 5-HT3 receptors mediate the cancer chemotherapeutic-enhanced gastric retention of solid material in rats. This implicates that the gastric retention of solid material is a useful marker to predict the potential of compounds to induce nausea and/or emesis in non-vomiting rodents. PMID:22687994

  2. ABCG2 Is a Selectable Marker for Enhanced Multilineage Differentiation Potential in Periodontal Ligament Stem Cells

    PubMed Central

    Szepesi, Áron; Matula, Zsolt; Szigeti, Anna; Várady, György; Szabó, Gyula; Uher, Ferenc; Sarkadi, Balázs

    2015-01-01

    Periodontal ligament stem cells (PDLSCs) provide an important source for tissue regeneration and may become especially useful in the formation of osteogenic seeds. PDLSCs can be cultured, expanded, and differentiated in vitro; thus, they may be applied in the long-term treatment of the defects in the dental regions. Here we studied numerous potential markers allowing the selection of human PDLSCs with a maximum differentiation potential. We followed the expression of the ATP-binding cassette subfamily G member 2 (ABCG2) membrane transporter protein and isolated ABCG2-expressing cells by using a monoclonal antibody, recognizing the transporter at the cell surface in intact cells. The expression of the ABCG2 protein, corresponding to the so-called side-population phenotype in various tissue-derived stem cells, was found to be a useful marker for the selection of PDLSCs with enhanced osteogenic, chondrogenic, and adipogenic differentiation. These findings may have important applications in achieving efficient dental tissue regeneration by using stem cells from extracted teeth. PMID:25101689

  3. Predictive potential of microsatellite markers on heterosis of fecundity in crossbred sheep.

    PubMed

    Di, R; Chu, M X; Li, Y L; Zhang, L; Fang, L; Feng, T; Cao, G L; Chen, H Q; Li, X W

    2012-03-01

    Small Tail Han (STH) sheep is a famous Chinese local breed and has perfect prolificacy performance, but it is inferior to imported mutton sheep breeds on meat production. In this study, six imported male sheep populations (White Suffolk, Black Suffolk, Texel, Dorper, South African Mutton Merino and East Friesian) were crossbred with STH female sheep respectively. The heterosis values of litter size, average daily gain (ADG) and feed conversion ratio (FCR) of crossbred sheep were analyzed for seeking the optimal cross. Meanwhile 28 microsatellite markers were used to measure the genetic distance between imported populations and STH population. Regression between the genetic distance and heterosis was analyzed for evaluating potential of microsatellite on predicting heterosis. Results showed a significant positive linear correlation (r = 0.892, P < 0.05) between heterosis of litter size and genetic distance D (A) of six crosses. This implied that these microsatellite markers had moderate potential to forecast heterosis of litter size in sheep. Results of this study also indicated that South African Mutton Merino and East Friesian sheep would be the optimal sire breeds for the litter size and might bring the greatest economic benefit in six imported populations; Suffolk sheep could be prior consideration as sire breeds when breeding objective focused on ADG. Finally these results provided valuable information for Chinese sheep industry. PMID:21674186

  4. Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines.

    PubMed

    Okamoto, Yoshihiko; Ohkubo, Tsuyako; Ikebe, Tetsuro; Yamazaki, Jun

    2012-05-01

    Several members of the transient receptor potential (TRP)-channel family are expressed in cancer cells. One, cold/menthol-sensitive TRPM8, is reportedly an important player in carcinogenesis in human prostate cancer, although its involvement in oral squamous cell carcinoma (SCC) remains unclear. The present immunohistochemistry and RT-PCR results revealed intense TRPM8 expression in two SCC cell lines, HSC3 and HSC4, derived from the human tongue. Menthol, icilin, and a more specific TRPM8 agonist (WS-12) induced non-specific cation currents, with Ca2+ permeability being greater than that of Na+ or K+. The novel TRPM8 antagonist RQ-00203078 (RQ) profoundly reduced such agonist-induced cation currents. Intracellular Ca2+ imaging revealed that menthol induced both intracellular Ca2+ release and store-operated Ca2+ entry, with RQ inhibiting each effect. To assess the possible pathophysiological role of TRPM8 in oral SCC, we performed motility and invasion assays, and gelatin zymography. Menthol augmented the migration and invasion abilities of both HSC3 and HSC4 cells by potentiating MMP-9 activity. RQ suppressed all of these effects. These results may aid understanding of the pathophysiological implications of TRPM8 channels in the oral SCC cells, support TRP proteins as valuable targets for pharmaceutical intervention, and inform the targeting of oral SCC in which the prognosis is poor. PMID:22267123

  5. Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology1

    PubMed Central

    Robarts, Daniel W. H.; Wolfe, Andrea D.

    2014-01-01

    In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance. PMID:25202637

  6. 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

  7. [THE SOMATIC MUTATIONS AND ABERRANT METHYLATION AS POTENTIAL GENETIC MARKERS OF URINARY BLADDER CANCER].

    PubMed

    Mikhailenko, D S; Kushlinskii, N E

    2016-02-01

    All around the world, more than 330 thousands cases of bladder cancer are registered annually hence representing actual problem of modern oncology. Still in demand are search and characteristic of new molecular markers of bladder cancer detecting in tumor cells from urinary sediment and having high diagnostic accuracy. The studies of last decade, especially using methods of genome-wide sequencing, permitted to receive a large amount of experimental data concerning development and progression of bladder cancer The review presents systematic analysis of publications available in PubMed data base mainly of last five years. The original studies of molecular genetic disorders under bladder cancer and meta-analyzes were considered This approach permitted to detected the most common local alterations of DNA under bladder cancer which can be detected using routine genetic methods indifferent clinical material and present prospective interest for development of test-systems. The molecular genetic markers of disease can be activating missense mutations in 7 and 10 exons of gene of receptor of growth factor of fibroblasts 3 (FGFR3), 9 and 20 exons of gene of Phosphatidylinositol-4,5-bi-phosphate-3-kinase (PIK3CA) and mutation in -124 and -146 nucleotides in promoter of gene of catalytic subunit telomerase (TERT). The development of test-systems on the basis of aberrant methylation of CpG-islets of genes-suppressors still is seemed as a difficult task because of differences in pattern of methylation of different primary tumors at various stages of clonal evolution of bladder cancer though they can be considered as potential markers. PMID:27455559

  8. Trehalose as an indicator of desiccation stress in Drosophila melanogaster larvae: A potential marker of anhydrobiosis

    SciTech Connect

    Thorat, Leena J.; Gaikwad, Sushama M.; Nath, Bimalendu B.

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer First report confirming anhydrobiosis in Drosophila melanogaster larvae. Black-Right-Pointing-Pointer Trehalose synthesis and accumulation in larvae that hydrolyzed on rehydration. Black-Right-Pointing-Pointer Trehalose synthesis in concert with the enzymes involved in trehalose metabolism. Black-Right-Pointing-Pointer Inhibition of trehalose hydrolysis in presence of a specific trehalase inhibitor. Black-Right-Pointing-Pointer Trehalose proposed as a reliable marker for biomonitoring of climate change studies. -- Abstract: In the current scenario of global climate change, desiccation is considered as one of the major environmental stressors for the biota exposed to altered levels of ambient temperature and humidity. Drosophila melanogaster, a cosmopolitan terrestrial insect has been chosen as a humidity-sensitive bioindicator model for the present study since its habitat undergoes frequent stochastic and/or seasonally aggravated dehydration regimes. We report here for the first time the occurrence of anhydrobiosis in D. melanogaster larvae by subjecting them to desiccation stress under laboratory conditions. Larvae desiccated for ten hours at <5% relative humidity could enter anhydrobiosis and could revive upon rehydration followed by resumption of active metabolism. As revealed by FTIR and HPLC analyzes, our findings strongly indicated the synthesis and accumulation of trehalose in the desiccating larvae. Biochemical measurements pointed out the desiccation-responsive trehalose metabolic pathway that was found to be coordinated in concert with the enzymes trehalose 6-phosphate synthase and trehalase. Further, an inhibitor-based experimental approach using deoxynojirimycin, a specific trehalase inhibitor, demonstrated the pivotal role of trehalose in larval anhydrobiosis of D. melanogaster. We therefore propose trehalose as a potential marker for the assessment of anhydrobiosis in Drosophila. The present findings thus add

  9. Characterization, Localization and Patterning of Lymphatics and Blood Vessels in Oral Squamous Cell Carcinoma: A Comparative Study Using D2-40 and CD-34 IHC Marker

    PubMed Central

    Agarwal, Deshant; Bajpai, Manas; Gupta, Shailendra; Mathur, Nikunj; Vanaki, S S; Puranik, R S; Mittal, Manoj

    2014-01-01

    Objectives: Lymphatic metastasis has always been regarded as a major prognostic indicator for disease progression and as a guide for therapeutic strategies to oral squamous cell carcinoma (OSCC). Differentiating lymphatic vessels from blood vessels is difficult, partly due to lack of specific method for identifying lymphatics. A new lymphatic vessel reactive antibody D2-40 has been introduced recently. Here we examined immunohistochemical localization of lymphatic vessels and blood vessels using D2-40 and CD-34 respectively in different histological grades of OSCC. Their expression in intra-tumoural and peri-tumoural region was also compared. Materials and Methods: Forty two formalin-fixed paraffin-embedded tissue blocks of excised specimens of OSCC were immunohistochemically evaluated using D2-40 and CD-34 antibodies. Lymphatic vessel density (LVD) (D2-40 positivity) and micro vessel density (MVD) (CD34 positivity) in both intratumoural and peritumoural areas were assessed by hot spot method. Results: Regardless of histopathological differentiation, LVD–– and MVD in peritumoural areas were found greater than intratumoural areas (p>0.05). Interestingly, other than lymphatic vessels, D2-40 positivity was also detected in tumour cells as well as in basal layer of epithelium adjacent to OSCC. Two patterns of distribution of CD34 positive vessel - circumscribing type and penetrating type were also observed in the cancer nest area. Conclusion: D2-40 can be used as a marker to differentiate lymphatic vessels from blood vessels. Lymphatic and blood vessel proliferation might be much more extensive in the peritumoural area. D2-40 expression in epithelium adjacent to tumour indicates its role in the process of differentiation. Further, its expression in potential malignant disorder may provide better insight in predicting prognosis and pathogenesis of these lesions. PMID:25478456

  10. Glycated serum albumin: a potential disease marker and an intermediate index of diabetes control.

    PubMed

    Raghav, Alok; Ahmad, Jamal

    2014-01-01

    Glycation is a non-enzymatic spontaneous process in proteins which has remarkable impact on its physical and functional aspect. This alteration with addition of carbohydrate residue to human serum albumin leads to several pathological events such as diabetic nephropathy, neuropathy, retinopathy and cardiovascular complications. Human serum albumin is the major protein and is most susceptible to non-enzymatic glycation. Structural and biological properties of functional albumin alter due to the addition of reducing carbohydrate to free amino terminal residues vivo. These irreversible changes in functional albumin are stable which makes this modified albumin as new gold standard future diagnostic marker in diabetes associated complications. Glycated albumin can be used to determine the glycemic control due to short half life than erythrocytes which makes it an alternate reliable disease marker in diabetes. In this review, Human serum albumin glycation has been overviewed, stating concept of glycation and sites that are prone to this modifications. Impact of non-enzymatic addition of carbohydrate to albumin's structural and biological properties has also been elaborated. Accurate measurements of glycated albumin with implications of new highly sensitive techniques have also been described briefly. Interestingly human serum albumin imposed glycation can serve as future tool not for diagnosing diabetes but also its potential in assessment of diabetes associated complications. PMID:25311816

  11. Identification of Meflin as a Potential Marker for Mesenchymal Stromal Cells

    PubMed Central

    Maeda, Keiko; Enomoto, Atsushi; Hara, Akitoshi; Asai, Naoya; Kobayashi, Takeshi; Horinouchi, Asuka; Maruyama, Shoichi; Ishikawa, Yuichi; Nishiyama, Takahiro; Kiyoi, Hitoshi; Kato, Takuya; Ando, Kenju; Weng, Liang; Mii, Shinji; Asai, Masato; Mizutani, Yasuyuki; Watanabe, Osamu; Hirooka, Yoshiki; Goto, Hidemi; Takahashi, Masahide

    2016-01-01

    Bone marrow-derived mesenchymal stromal cells (BM-MSCs) in culture are derived from BM stromal cells or skeletal stem cells. Whereas MSCs have been exploited in clinical medicine, the identification of MSC-specific markers has been limited. Here, we report that a cell surface and secreted protein, Meflin, is expressed in cultured MSCs, fibroblasts and pericytes, but not other types of cells including epithelial, endothelial and smooth muscle cells. In vivo, Meflin is expressed by immature osteoblasts and chondroblasts. In addition, Meflin is found on stromal cells distributed throughout the BM, and on pericytes and perivascular cells in multiple organs. Meflin maintains the undifferentiated state of cultured MSCs and is downregulated upon their differentiation, consistent with the observation that Meflin-deficient mice exhibit increased number of osteoblasts and accelerated bone development. In the bone and BM, Meflin is more highly expressed in primitive stromal cells that express platelet-derived growth factor receptor α and Sca-1 than the Sca-1-negative adipo-osteogenic progenitors, which create a niche for hematopoiesis. Those results are consistent with a decrease in the number of clonogenic colony-forming unit-fibroblasts within the BM of Meflin-deficient mice. These preliminary data suggest that Meflin is a potential marker for cultured MSCs and their source cells in vivo. PMID:26924503

  12. Identification of Meflin as a Potential Marker for Mesenchymal Stromal Cells.

    PubMed

    Maeda, Keiko; Enomoto, Atsushi; Hara, Akitoshi; Asai, Naoya; Kobayashi, Takeshi; Horinouchi, Asuka; Maruyama, Shoichi; Ishikawa, Yuichi; Nishiyama, Takahiro; Kiyoi, Hitoshi; Kato, Takuya; Ando, Kenju; Weng, Liang; Mii, Shinji; Asai, Masato; Mizutani, Yasuyuki; Watanabe, Osamu; Hirooka, Yoshiki; Goto, Hidemi; Takahashi, Masahide

    2016-01-01

    Bone marrow-derived mesenchymal stromal cells (BM-MSCs) in culture are derived from BM stromal cells or skeletal stem cells. Whereas MSCs have been exploited in clinical medicine, the identification of MSC-specific markers has been limited. Here, we report that a cell surface and secreted protein, Meflin, is expressed in cultured MSCs, fibroblasts and pericytes, but not other types of cells including epithelial, endothelial and smooth muscle cells. In vivo, Meflin is expressed by immature osteoblasts and chondroblasts. In addition, Meflin is found on stromal cells distributed throughout the BM, and on pericytes and perivascular cells in multiple organs. Meflin maintains the undifferentiated state of cultured MSCs and is downregulated upon their differentiation, consistent with the observation that Meflin-deficient mice exhibit increased number of osteoblasts and accelerated bone development. In the bone and BM, Meflin is more highly expressed in primitive stromal cells that express platelet-derived growth factor receptor α and Sca-1 than the Sca-1-negative adipo-osteogenic progenitors, which create a niche for hematopoiesis. Those results are consistent with a decrease in the number of clonogenic colony-forming unit-fibroblasts within the BM of Meflin-deficient mice. These preliminary data suggest that Meflin is a potential marker for cultured MSCs and their source cells in vivo. PMID:26924503

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

    PubMed

    Mattheos, N

    2007-08-01

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

  14. 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

  15. 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

  16. A Case-Control Study of Oral Epithelial Proliferative Markers among Sudanese Toombak Dippers Using Micronuclei Assay, Argyrophilic Nucleolar Organizer Region, Papanicolaou and Crystal Violet Methods

    PubMed Central

    Anass, M. Abbas; G. Ahmed, Hussain

    2013-01-01

    The use of Toombak has been reported to play a major role in the etiology of oral cancer in Sudan. The cellular proliferative activity on the oral epithelium of 210 Toombak dippers was assessed by applying the micronuclei frequency, mean argyrophilic nucleolar organizer region (AgNOR) counts, Papanicolaou method, and 1% crystal violet stain. Participants were divided into 3 groups: 200 were apparently healthy individuals, 100 were Toombak users (cases), 100 were non-tobacco users (control) and 10 were patients with oral squamous cell carcinomas. Cytological atypia was identified among 4 (4%). Toombak users and was not found among the control group (P<0.04). The micronuclei frequencies were higher in Toombak users (1.026) than in the control group (0.356) (P<0.0001). The mean AgNOR counts in Toombak users (2.423) were higher than control group (1.303) (P<0.0001). Neither Toombak users nor control group showed mitotic figures in 1% crystal violet method. The results of this research showed that Toombak dipping is a high risk factor for increase in the cellular proliferation in the oral mucosa. The cytological proliferative marker methods used are useful for screening Toombak users. PMID:24179643

  17. Neck circumference as a potential marker of metabolic syndrome among college students1

    PubMed Central

    Pereira, Dayse Christina Rodrigues; de Araújo, Márcio Flávio Moura; de Freitas, Roberto Wagner Júnior Freire; Teixeira, Carla Regina de Souza; Zanetti, Maria Lúcia; Damasceno, Marta Maria Coelho

    2014-01-01

    OBJECTIVE: to relate neck circumference with metabolic syndrome and its criteria among college students. METHOD: cross-sectional study conducted with 702 college students in Fortaleza, CE, Brazil from September 2010 to June 2011. Socio-demographic data, waist circumference and neck circumference were collected together with blood pressure, fasting blood sugar, triglyceride levels, and HDL-C. RESULTS: 1.7% of the studied sample presented metabolic syndrome. Of these, 58.3% presented altered neck circumference (p<0.006). As neck circumference decreases, pressure levels improve (p<0.001). Additionally, college students with high fasting blood sugar (p=0.003) and high triglyceride levels (p<0.001) presented higher values of neck circumference. CONCLUSION: neck circumference is a potential predictive marker in the detection of metabolic syndrome and its components among college students. PMID:25591092

  18. Corpus Callosum Pathology as a Potential Surrogate Marker of Cognitive Impairment in Diffuse Axonal Injury.

    PubMed

    Ubukata, Shiho; Ueda, Keita; Sugihara, Genichi; Yassin, Walid; Aso, Toshihiko; Fukuyama, Hidenao; Murai, Toshiya

    2016-01-01

    Diffuse axonal injury is a major form of traumatic brain injury. Neuropsychological assessments and high-resolution structural MRI were conducted using T1-weighted and diffusion tensor imaging. This study included 10 patients with diffuse axonal injury (all men, mean age 30.8±10.5 years) and 12 age- and sex-matched normal control participants. Patients with diffuse axonal injury had widespread volume reductions and lower fractional anisotropy in the corpus callosum (CC) compared with controls. Furthermore, cognitive processing speed was associated with reductions in white matter volume and fractional anisotropy in the CC. These findings suggest that CC pathology may be a potential surrogate marker of the cognitive deficits in these patients. PMID:26569151

  19. Genotyping in the MHC locus: potential for defining predictive markers in sarcoidosis

    PubMed Central

    Seitzer, Ulrike; Gerdes, Johannes; Müller-Quernheim, Joachim

    2002-01-01

    In sarcoidosis, host genetic factors are discussed as contributing to disease susceptibility and course. Since tumor necrosis factor (TNF)-α is a central mediator of granuloma formation and since elevated TNF-α levels are found during active phases of sarcoidosis, genetic polymorphisms correlating with influences on TNF-α levels are of special interest. The complete sequencing of the MHC region and the increase in the number of identified gene polymorphisms in this locus associated with TNF-α production offer the opportunity of detecting new genes associated with sarcoidosis and perhaps of defining disease-associated haplotypes that bear the potential of serving as predictive markers for this disease. PMID:11806841

  20. The Effects of Long-Term Oral Benfotiamine Supplementation on Peripheral Nerve Function and Inflammatory Markers in Patients With Type 1 Diabetes

    PubMed Central

    Fraser, David A.; Diep, Lien M.; Hovden, Inger Anette; Nilsen, Kristian B.; Sveen, Kari Anne; Seljeflot, Ingebjørg; Hanssen, Kristian F.

    2012-01-01

    OBJECTIVE To study the effects of long-term oral benfotiamine supplementation on peripheral nerve function and soluble inflammatory markers in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS The study randomly assigned 67 patients with type 1 diabetes to receive 24-month benfotiamine (300 mg/day) or placebo supplementation. Peripheral nerve function and levels of soluble inflammatory variables were assessed at baseline and at 24 months. RESULTS Fifty-nine patients completed the study. Marked increases in whole-blood concentrations of thiamine and thiamine diphosphate were found in the benfotiamine group (both P < 0.001 vs. placebo). However, no significant differences in changes in peripheral nerve function or soluble inflammatory biomarkers were observed between the groups. CONCLUSIONS Our findings suggest that high-dose benfotiamine (300 mg/day) supplementation over 24 months has no significant effects upon peripheral nerve function or soluble markers of inflammation in patients with type 1 diabetes. PMID:22446172

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

    PubMed Central

    2014-01-01

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

  2. Immune dysregulation mediated by the oral microbiome: potential link to chronic inflammation and atherosclerosis.

    PubMed

    Slocum, C; Kramer, C; Genco, C A

    2016-07-01

    Cardiovascular disease is an inflammatory disorder characterized by the progressive formation of plaque in coronary arteries, termed atherosclerosis. It is a multifactorial disease that is one of the leading causes of death worldwide. Although a number of risk factors have been associated with disease progression, the underlying inflammatory mechanisms contributing to atherosclerosis remain to be fully delineated. Within the last decade, the potential role for infection in inflammatory plaque progression has received considerable interest. Microbial pathogens associated with periodontal disease have been of particular interest due to the high levels of bacteremia that are observed after routine dental procedures and every day oral activities, such as tooth brushing. Here, we explore the potential mechanisms that may explain how periodontal pathogens either directly or indirectly elicit immune dysregulation and consequently progressive inflammation manifested as atherosclerosis. Periodontal pathogens have been shown to contribute directly to atherosclerosis by disrupting endothelial cell function, one of the earliest indicators of cardiovascular disease. Oral infection is thought to indirectly induce elevated production of inflammatory mediators in the systemic circulation. Recently, a number of studies have been conducted focusing on how disruption of the gut microbiome influences the systemic production of proinflammatory cytokines and consequently exacerbation of inflammatory diseases such as atherosclerosis. It is clear that the immune mechanisms leading to atherosclerotic plaque progression, by oral infection, are complex. Understanding the immune pathways leading to disease progression is essential for the future development of anti-inflammatory therapies for this chronic disease. PMID:26791914

  3. SPR imaging biosensor for determination of laminin-5 as a potential cancer marker in biological material.

    PubMed

    Sankiewicz, A; Romanowicz, L; Laudanski, P; Zelazowska-Rutkowska, B; Puzan, B; Cylwik, B; Gorodkiewicz, E

    2016-07-01

    A new method for the selective determination of laminin-5 concentration using a biosensor and surface plasmon resonance imaging (SPRI) technique is presented. A biosensor based on the specific interaction of laminin-5 with rabbit polyclonal antibody was constructed. The analytically useful dynamic response range of the biosensor is between 0.014 and 0.1 ng mL(-1). The detection limit is 4 pg mL(-1). The potential influence of interferences on the SPRI signal was investigated, and the high selectivity of the biosensor was confirmed. In order to demonstrate the potential application of the biosensor, laminin-5 concentration in blood plasma was determined. The results were compared with the laminin-5 concentration obtained by the commercial enzyme-linked immunosorbent assay (ELISA) kit. A comparison of results from healthy donors obtained by SPRI measurement and ELISA indicates that they are close and shows good agreement with the data reported in the literature. The plasma samples of bladder cancer patients gave higher concentration measured with specific biosensor than by ELISA assay. The study shows the clear difference in concentration of laminin-5 in healthy humans and patients with bladder cancer. Extensive clinical studies using the newly developed method can result in an increase in the use of laminin-5 as a potential cancer marker. PMID:27209594

  4. Evaluation of Potential Clinical Surrogate Markers of a Trauma Induced Alteration of Clotting Factor Activities

    PubMed Central

    Payas, Arzu; Schoeneberg, Carsten; Wegner, Alexander; Kauther, Max Daniel; Lendemans, Sven

    2016-01-01

    Objective. The aim of this study was to identify routinely available clinical surrogate markers for potential clotting factor alterations following multiple trauma. Methods. In 68 patients admitted directly from the scene of the accident, all soluble clotting factors were analyzed and clinical data was collected prospectively. Ten healthy subjects served as control group. Results. Patients showed reduced activities of clotting factors II, V, VII, and X and calcium levels (all P < 0.0001 to 0.01). Levels of hemoglobin and base deficit correlated moderately to highly with the activities of a number of clotting factors. Nonsurvivors and patients who needed preclinical intubation or hemostatic therapy showed significantly reduced factor activities at admission. In contrast, factor VIII activity was markedly elevated after injury in general (P < 0.0001), but reduced in nonsurvivors (P < 0.05). Conclusions. Multiple trauma causes an early reduction of the activities of nearly all soluble clotting factors in general. Initial hemoglobin and, with certain qualifications, base deficit levels demonstrated a potential value in detecting those underlying clotting factor deficiencies. Nevertheless, their role as triggers of a hemostatic therapy as well as the observed response of factor VIII to multiple trauma and also its potential prognostic value needs further evaluation. PMID:27433474

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

    Smoking is recognized as a health problem worldwide and there is an established tobacco epidemic in Saudi Arabia as in many other countries, with tobacco users at increased risk of developing many diseases. This cross sectional study was conducted to assess the prevalence of oral mucosal, potentially malignant or malignant, lesions associated with tobacco use among a stratified cluster sample of adults in Jeddah, Saudi Arabia. A sample size of 599 was collected and each participant underwent clinical conventional oral examination and filled a questionnaire providing information on demographics, tobacco use and other relevant habits. The most common form of tobacco used was cigarette smoking (65.6 %) followed by Shisha or Moasel (38.1%), while chewing tobacco, betel nuts and gat accounted for 21-2%, 7.7%, and 5% respectively. A high prevalence (88.8%) of soft tissue lesions was found among the tobacco users examined, and a wide range of lesions were detected, about 50% having hairy tongue, 36% smoker's melanosis, 28.9% stomatitis nicotina, 27% frictional keratosis, 26.7% fissured tongue, 26% gingival or periodontal inflammation and finally 20% leukodema. Suspicious potentially malignant lesions affected 10.5% of the subjects, most prevalent being keratosis (6.3%), leukoplakia (2.3%), erythroplakia (0.7%), oral submucous fibrosis (0.5%) and lichenoid lesions (0.4%), these being associated with male gender, lower level of education, presence of diabetes and a chewing tobacco habit. It is concluded that smoking was associated with a wide range of oral mucosal lesions , those suspicious for malignancy being linked with chewable forms, indicating serious effects. PMID:24568491

  7. Soluble receptor for advanced glycation end products: from disease marker to potential therapeutic target.

    PubMed

    Geroldi, Diego; Falcone, Colomba; Emanuele, Enzo

    2006-01-01

    The receptor for advanced glycation end products (RAGE) is a cell-bound receptor of the immunoglobulin superfamily which may be activated by a variety of proinflammatory ligands including advanced glycoxidation end products, S100/calgranulins, high mobility group box 1, and amyloid beta-peptide. RAGE has a secretory splice isoform, soluble RAGE (sRAGE), that lacks the transmembrane domain and therefore circulates in plasma. By competing with cell-surface RAGE for ligand binding, sRAGE may contribute to the removal/neutralization of circulating ligands thus functioning as a decoy. Clinical studies have recently shown that higher plasma levels of sRAGE are associated with a reduced risk of coronary artery disease, hypertension, the metabolic syndrome, arthritis and Alzheimer's disease. Increasing the production of plasma sRAGE is therefore considered to be a promising therapeutic target that has the potential to prevent vascular damage and neurodegeneration. This review presents the state of the art in the use of sRAGE as a disease marker and discusses the therapeutic potential of targeting sRAGE for the treatment of inflammation-related diseases such as atherosclerosis, arthritis and Alzheimer's disease. PMID:16842191

  8. 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

  9. Lipoprotein-associated phospholipase A2: a novel marker of cardiovascular risk and potential therapeutic target.

    PubMed

    Macphee, Colin; Benson, G Martin; Shi, Yi; Zalewski, Andrew

    2005-06-01

    Although the clinical benefit of statins is well established, these agents reduce the risk of cardiovascular events by only 20 - 40%, and the residual risk for high-risk patients is considerable. The recognition of atherosclerosis as an inflammatory disease has opened the door to numerous complementary therapeutic approaches to further reduce risk and the overall burden of cardiovascular disease. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a novel inflammatory marker of cardiovascular risk that is being evaluated as a potential therapeutic target. The biological function of this enzyme in atherosclerosis has been controversial but recent evidence supports its pro-atherogenic role. The enzyme is predominantly bound to low-density lipoprotein cholesterol particles in humans, and its activity produces bioactive lipid mediators that promote inflammatory processes present at every stage of atherogenesis, from atheroma initiation to plaque destabilisation and rupture. Initial clinical studies suggest that the inhibitors of Lp-PLA(2) can block enzyme activity in plasma and within atherosclerotic plaques. However, more studies are needed to determine the potential clinical benefits of inhibiting Lp-PLA(2). PMID:16004595

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. 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

  13. 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. PMID:26206324

  14. Metabolomics Profiling for Identification of Novel Potential Markers in Early Prediction of Preeclampsia

    PubMed Central

    Kuc, Sylwia; Koster, Maria P. H.; Pennings, Jeroen L. A.; Hankemeier, Thomas; Berger, Ruud; Harms, Amy C.; Dane, Adrie D.; Schielen, Peter C. J. I.; Visser, Gerard H. A.; Vreeken, Rob J.

    2014-01-01

    Objective The first aim was to investigate specific signature patterns of metabolites that are significantly altered in first-trimester serum of women who subsequently developed preeclampsia (PE) compared to healthy pregnancies. The second aim of this study was to examine the predictive performance of the selected metabolites for both early onset [EO-PE] and late onset PE [LO-PE]. Methods This was a case-control study of maternal serum samples collected between 8+0 and 13+6 weeks of gestation from 167 women who subsequently developed EO-PE n = 68; LO-PE n = 99 and 500 controls with uncomplicated pregnancies. Metabolomics profiling analysis was performed using two methods. One has been optimized to target eicosanoids/oxylipins, which are known inflammation markers and the other targets compounds containing a primary or secondary biogenic amine group. Logistic regression analyses were performed to predict the development of PE using metabolites alone and in combination with first trimester mean arterial pressure (MAP) measurements. Results Two metabolites were significantly different between EO-PE and controls (taurine and asparagine) and one in case of LO-PE (glycylglycine). Taurine appeared the most discriminative biomarker and in combination with MAP predicted EO-PE with a detection rate (DR) of 55%, at a false-positive rate (FPR) of 10%. Conclusion Our findings suggest a potential role of taurine in both PE pathophysiology and first trimester screening for EO-PE. PMID:24873829

  15. A hierarchy of event-related potential markers of auditory processing in disorders of consciousness.

    PubMed

    Beukema, Steve; Gonzalez-Lara, Laura E; Finoia, Paola; Kamau, Evelyn; Allanson, Judith; Chennu, Srivas; Gibson, Raechelle M; Pickard, John D; Owen, Adrian M; Cruse, Damian

    2016-01-01

    Functional neuroimaging of covert perceptual and cognitive processes can inform the diagnoses and prognoses of patients with disorders of consciousness, such as the vegetative and minimally conscious states (VS;MCS). Here we report an event-related potential (ERP) paradigm for detecting a hierarchy of auditory processes in a group of healthy individuals and patients with disorders of consciousness. Simple cortical responses to sounds were observed in all 16 patients; 7/16 (44%) patients exhibited markers of the differential processing of speech and noise; and 1 patient produced evidence of the semantic processing of speech (i.e. the N400 effect). In several patients, the level of auditory processing that was evident from ERPs was higher than the abilities that were evident from behavioural assessment, indicating a greater sensitivity of ERPs in some cases. However, there were no differences in auditory processing between VS and MCS patient groups, indicating a lack of diagnostic specificity for this paradigm. Reliably detecting semantic processing by means of the N400 effect in passively listening single-subjects is a challenge. Multiple assessment methods are needed in order to fully characterise the abilities of patients with disorders of consciousness. PMID:27595064

  16. Gpnmb Is a Potential Marker for the Visceral Pathology in Niemann-Pick Type C Disease

    PubMed Central

    Aten, Jan; van Roomen, Cindy P. A. A.; Ottenhoff, Roelof; Claessen, Nike; Alfonso, Pilar; Irún, Pilar; Giraldo, Pilar; Aerts, Johannes M. F. G.; van Eijk, Marco

    2016-01-01

    Impaired function of NPC1 or NPC2 lysosomal proteins leads to the intracellular accumulation of unesterified cholesterol, the primary defect underlying Niemann-Pick type C (NPC) disease. In addition, glycosphingolipids (GSLs) accumulate in lysosomes as well. Intralysosomal lipid accumulation triggers the activation of a set of genes, including potential biomarkers. Transcript levels of Gpnmb have been shown to be elevated in various tissues of an NPC mouse model. We speculated that Gpnmb could serve as a marker for visceral lipid accumulation in NPC disease. We report that Gpnmb expression is increased at protein level in macrophages in the viscera of Npc1nih/nih mice. Interestingly, soluble Gpnmb was also found to be increased in murine and NPC patient plasma. Exposure of RAW264.7 macrophages to the NPC-phenotype-inducing drug U18666A also upregulated Gpnmb expression. Inhibition of GSL synthesis with the glucosylceramide synthase (GCS) inhibitor N-butyl-1-deoxynojirimycin prevented U18666A-induced Gpnmb induction and secretion. In summary, we show that Gpnmb is upregulated in NPC mice and patients, most likely due to GSL accumulation. PMID:26771826

  17. Automated Video Analysis of Handwashing Behavior as a Potential Marker of Cognitive Health in Older Adults.

    PubMed

    Ashraf, Ahmed; Taati, Babak

    2016-03-01

    The identification of different stages of cognitive impairment can allow older adults to receive timely care and plan for the level of caregiving. People with existing diagnosis of cognitive impairment go through episodic phases of dementia requiring different levels of care at different times. Monitoring the cognitive status of existing patients is, thus, critical to deciding the level of care required by older adults. In this paper, we present a system to assess the cognitive status of older adults by monitoring a common activity of daily living, namely handwashing. Specifically, we extract features from handwashing trials of participants diagnosed with different levels of dementia ranging from cognitively intact to severe cognitive impairment, as assessed by the mini-mental state exam (MMSE). Based on videos of handwashing trials, we extract two classes of features: one characterizing the occupancy of different sink regions by the participant, and the other capturing the path tortuosity of the motion trajectory of participant's hands. We perform correlation analysis to assess univariate capacity of individual features to predict MMSE scores. To assess multivariate performance, we use machine learning methods to train models that predict the cognitive status (aware, mild, moderate, severe), as well as the MMSE scores. We present results demonstrating that features derived from hand washing behavior can be potential surrogate markers of a person's dementia, which can be instrumental in developing automated tools for continuously monitoring the cognitive status of older adults. PMID:25794404

  18. Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer.

    PubMed

    Kamel, Azza M; Teama, Salwa; Fawzy, Amal; El Deftar, Mervat

    2016-06-01

    Plasma DNA integrity index is increased in various malignancies including breast cancer, the most common cancer in women worldwide; early detection is crucial for successful treatment. Current screening methods fail to detect many cases of breast cancer at an early stage. In this study, we evaluated the level of plasma DNA integrity index in 260 females (95 with breast cancer, 95 with benign breast lesions, and 70 healthy controls) to verify its potential value in discriminating malignant from benign breast lesions. The criteria of the American Joint Committee on Cancer were used for staging of breast cancer patients. DNA integrity index was measured by real-time PCR. DNA integrity index was significantly higher in breast cancer than in benign breast patients and healthy subjects (P = <0.001). DNA integrity index is correlated with TNM stage. Given 100 % specificity, the highest sensitivity achieved in detecting cancer group was 85.3 % at 0.55 DNA integrity index cutoff. In conclusion, the plasma DNA integrity index may be a promising molecular diagnostic marker of malignancy in breast lesions. PMID:26684805

  19. Assessment of volatile profile as potential marker of chilling injury of basil leaves during postharvest storage.

    PubMed

    Cozzolino, Rosaria; Pace, Bernardo; Cefola, Maria; Martignetti, Antonella; Stocchero, Matteo; Fratianni, Florinda; Nazzaro, Filomena; De Giulio, Beatrice

    2016-12-15

    The volatile profile of three sweet basil cultivars, "Italico a foglia larga", "Cammeo" and "Italiano classico", packaged in air at 4 or 12°C until 9days, was monitored by solid phase microextraction with GC-MS. Chilling injury (CI) score and electrolyte leakage were also assessed. In total, 71 volatile organic compounds (VOCs) were identified in the headspace of basil samples. A preliminary principal component analysis highlighted the dominant effect of the cultivar on VOCs profiles. Data analysis by post-transformation of projection to latent structures regression (ptPLS2) clarified the role played by time and temperature of storage. Temperature influenced the emission of volatiles during storage, with much lower total volatile emissions at 4°C compared to 12°C. Finally, a ptPLS2 regression model performed on VOCs and the two CI parameters allowed selection of 10 metabolites inversely correlated to both CI parameters, which can be considered potential markers of CI in basil leaves. PMID:27451192

  20. Elevated amniotic fluid F₂-isoprostane: a potential predictive marker for preeclampsia.

    PubMed

    Wang, Chao-Nin; Chen, Jannie Ying-Syuan; Sabu, Sahadevan; Chang, Yao-Lung; Chang, Shuenn-Dyh; Kao, Chuan-Chi; Peng, Hsiu-Huei; Chueh, Ho-Yen; Chao, An-Shine; Cheng, Po-Jen; Lee, Yun-Shien; Chi, Lang-Ming; Wang, Tzu-Hao

    2011-05-01

    In the complex mechanism of preeclampsia, oxidative stress is an important pathogenic factor, and F₂-isoprostane is a marker of oxidative stress and lipid peroxidation. The objective of this study was to identify if the amniotic fluid (AF) levels of F₂-isoprostanes were elevated in women who later developed preeclampsia. In this study, we analyzed AF F₂-isoprostane concentrations with enzyme immunoassay (EIA), and the EIA results could be validated by quantitative mass spectrometry. The mean AF concentration of F₂-isoprostanes was significantly higher in pregnancies with subsequent development of preeclampsia (123.1 ± 57.6 pg/ml, n = 85) than in controls (73.8 ± 36.6 pg/ml, n = 85). The AF elevation of F₂-isoprostanes was even higher in the preeclampsia with intrauterine growth restriction group (138.3 ± 65.2 pg/ml, n = 39). The area under the curve of the receiver operating characteristics analysis for AF F₂-isoprostanes assay was 0.81, supporting its potential as a biomarker for preeclampsia. These results indicate that oxidative stress existed before the onset of clinical preeclampsia, further suggesting that the elevation of AF F₂-isoprostanes may be used as a guide for antioxidant supplementation to reduce the risk and/or severity of preeclampsia. PMID:21277370

  1. The Impact of AD Drug Treatments on Event-Related Potentials as Markers of Disease Conversion

    PubMed Central

    Chapman, Robert M.; Porsteinsson, Anton P.; Gardner, Margaret N.; Mapstone, Mark; McCrary, John W.; Sandoval, Tiffany C.; Guillily, Maria D.; Reilly, Lindsey A.; DeGrush, Elizabeth

    2013-01-01

    This paper investigates how commonly prescribed pharmacologic treatments for Alzheimer’s disease (AD) affect Event-Related Potential (ERP) biomarkers as tools for predicting AD conversion in individuals with Mild Cognitive Impairment (MCI). We gathered baseline ERP data from two MCI groups (those taking AD medications and those not) and later determined which subjects developed AD (Convert->AD) and which subjects remained cognitively stable (Stable). We utilized a previously developed and validated multivariate system of ERP components to measure medication effects among these four subgroups. Discriminant analysis produced classification scores for each individual as a measure of similarity to each clinical group (Convert->AD, Stable), and we found a large significant main Group effect but no main AD Medications effect and no Group by Medications interaction. This suggested AD medications have negligible influence on this set of ERP components as weighted markers of disease progression. These results provide practical information to those using ERP measures as a biomarker to identify and track AD in individuals in a clinical or research setting. PMID:23905997

  2. Gpnmb Is a Potential Marker for the Visceral Pathology in Niemann-Pick Type C Disease.

    PubMed

    Marques, André R A; Gabriel, Tanit L; Aten, Jan; van Roomen, Cindy P A A; Ottenhoff, Roelof; Claessen, Nike; Alfonso, Pilar; Irún, Pilar; Giraldo, Pilar; Aerts, Johannes M F G; van Eijk, Marco

    2016-01-01

    Impaired function of NPC1 or NPC2 lysosomal proteins leads to the intracellular accumulation of unesterified cholesterol, the primary defect underlying Niemann-Pick type C (NPC) disease. In addition, glycosphingolipids (GSLs) accumulate in lysosomes as well. Intralysosomal lipid accumulation triggers the activation of a set of genes, including potential biomarkers. Transcript levels of Gpnmb have been shown to be elevated in various tissues of an NPC mouse model. We speculated that Gpnmb could serve as a marker for visceral lipid accumulation in NPC disease. We report that Gpnmb expression is increased at protein level in macrophages in the viscera of Npc1nih/nih mice. Interestingly, soluble Gpnmb was also found to be increased in murine and NPC patient plasma. Exposure of RAW264.7 macrophages to the NPC-phenotype-inducing drug U18666A also upregulated Gpnmb expression. Inhibition of GSL synthesis with the glucosylceramide synthase (GCS) inhibitor N-butyl-1-deoxynojirimycin prevented U18666A-induced Gpnmb induction and secretion. In summary, we show that Gpnmb is upregulated in NPC mice and patients, most likely due to GSL accumulation. PMID:26771826

  3. Vitamin D receptor expression is linked to potential markers of human thyroid papillary carcinoma.

    PubMed

    Izkhakov, Elena; Somjen, Dalia; Sharon, Orli; Knoll, Esther; Aizic, Asaf; Fliss, Dan M; Limor, Rona; Stern, Naftali

    2016-05-01

    Genes regulated cell-cell and cell-matrix adhesion and degradation of the extracellular matrix (ECM) have been screened as potential markers of malignant thyroid nodules. The mRNA expression levels of two of them, the ECM protein-1 (ECM1) and the type II transmembrane serine protease-4 (TMPRSS4), were shown to be an independent predictor of an existing thyroid carcinoma. The vitamin D receptor (VDR) is expressed in epithelial cells of the normal thyroid gland, as well as in malignant dividing cells, which respond to the active metabolite of vitamin D by decreased proliferative activity in vitro. We evaluated the relationship between mRNA gene expressions of TMPRSS4, ECM1 and VDR in 21 papillary thyroid carcinoma samples and compared it to 21 normal thyroid tissues from the same patients. Gene expression was considered as up- or down-regulated if it varied by more or less than 2-fold in the cancer tissue relative to the normal thyroid tissue (Ca/N) from the same patient. We found an overall significant adjusted correlation between the mRNA expression ratio (ExR) of VDR and that of ECM1 in Ca/N thyroid tissue (R=0.648, P<0.001). There was a high ExR of VDR between Ca/N thyroid tissue from the same patient (3.06±2.9), which also exhibited a high Ca/N ExR of ECM1 and/or of TMPRSS4 (>2, P=0.05).The finding that increased VDR expression in human thyroid cancer cells is often linked to increased ECM1 and/or TPMRSS4 expression warrants further investigation into the potential role of vitamin D analogs in thyroid carcinoma. PMID:26907966

  4. Analysis of Potential Oral Cleft Risk Factors in the Kosovo Population

    PubMed Central

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

    2014-01-01

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

  5. Masculinizing effects on otoacoustic emissions and auditory evoked potentials in women using oral contraceptives.

    PubMed

    McFadden, D

    2000-04-01

    The otoacoustic emissions (OAEs) and auditory evoked potentials (AEPs) measured in two separate large scale studies were examined retrospectively for potential differences between those women using, and those not using, oral contraception (OC). Fourteen dependent variables were examined, all of which exhibited substantial sex differences. For 13 of those 14 dependent variables, the means for the users of OC were shifted away from the means of the non-users in the direction of the males. Specifically, for four different measures of OAE strength, for seven of eight measures of AEP latency or amplitude, and for two cognitive tests (mental rotation and water level), the means for the users of OC were located intermediate to those of the non-users of OC and the males. Few of these differences between users and non-users of OC achieved statistical significance, but the near universality of the direction of the difference suggests that oral contraceptives do produce a weak masculinizing effect on some auditory structures. These weak masculinizing effects appear to run contrary to the facts that the levels of both free testosterone and estradiol are lower in women using OC than in normal-cycling women. Past findings on auditory sex differences may have underestimated those sex differences. PMID:10748325

  6. 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

  7. 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

  8. Pharmacodynamic effects of oral contraceptive steroids on biochemical markers for arterial thrombosis. Studies in non-diabetic women and in women with insulin-dependent diabetes mellitus.

    PubMed

    Petersen, Kresten Rubeck

    2002-02-01

    Even small increases in the frequency of thrombotic disease in users of OCs have general health impact because of their widespread use, which is currently expanding to potential risk groups. The present investigations were launched to study the effects of OCs containing 20-40 micrograms of EE combined with the latest developed gonane progestogens on biochemical risk markers within metabolic systems involved in the development of arterial thrombotic disease. The studies included evaluation of carbohydrate and lipid metabolism as well as the haemostatic system and were performed in non-diabetic women and in women with IDDM, who are prone to the development of arterial thrombosis. In the evaluation of the carbohydrate metabolism in non-diabetic women, we found no effect on fasting glucose or insulin and no effect on the insulin response to oral glucose in women using monophasic OCs containing EE combined with DSG or GST. This contrasts the evaluation of triphasic OCs containing EE combined with GST or NGT, which increased fasting insulin and reduced insulin sensitivity without affecting the glucose-effectiveness or the beta-cell function. Impaired glucose tolerance developed in 10% of the women after 6 months. These finding suggest that OCs are able to induce a state of insulin resistance, which should be considered in the prescription for women with potential disturbed insulin sensitivity or reduced beta-cell secretory capacity e.g. women with ovarian hyperandrogenism, obesity, previous GDM or perimenopausal women. We found no change in glycaemic control in 22 women with well-regulated IDDM treated with a monophasic combination of EE and GST for one year and none of the women developed microalbuminuria during treatment. In the women with diabetes we observed an increase in fasting levels of triglycerides, a decrease in LDL-cholesterol, and unchanged concentrations of total cholesterol and HDL-cholesterol during treatment. In non-diabetic women treated with the same

  9. AMINOACYL FUCOSIDES AS POSSIBLE BIOCHEMICAL MARKERS OF TUMORIGENIC AND METASTATIC POTENTIAL IN HERPES SIMPLEX VIRUS TYPE 2-TRANSFORMED RAT CELLS

    EPA Science Inventory

    Two classes of aminoacyl fucosides termed F13 and F14 were studied as possible markers of tumorigenic and metastatic potential in herpes simplex virus type 2 transformed rat cells. In the present study, clonal cell lines of transformed highly tumorigenic and metastatic (t-REF-G-2...

  10. 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

  11. Congruence and indifference between two molecular markers for understanding oral evolution in the Marynidae sensu lato (Ciliophora, Colpodea)

    PubMed Central

    Dunthorn, Micah; Katz, Laura A.; Stoeck, Thorsten; Foissner, Wilhelm

    2012-01-01

    Our understanding of the evolution of oral structures within the Colpodida is confounded by the low number of morphological characters that can be used in constructing hypotheses, and by the low taxon and character sampling in molecular phylogenetic analyses designed to assess these hypotheses. Here we increase character sampling by sequencing the mitochondrial SSU-rDNA locus for three isolates of the Marynidae sensu lato. We show that the inferred mitochondrial and nuclear SSU-rDNA trees, as well as concatenated and constrained analyses, are congruent in not recovering a monophyletic Marynidae. However, due to low node support, the trees are indifferent to whether the morphological characters used to unite the Marynidae are the result of retention of ancestral states or convergence. In light of this indifference and an increased amount of nuclear and mitochondrial SSU-rDNA data, alternative hypotheses of oral evolution in the Colpodida are presented. PMID:22356924

  12. The potential role of antiplatelet agents in modulating inflammatory markers in atherothrombosis.

    PubMed

    Yeh, E T H; Khan, B V

    2006-11-01

    Atherothrombosis is the process that links atherosclerotic lesion development with unpredictable and life-threatening ischemic vascular events such as angina, myocardial infarction, transient ischemic attack, and stroke. Atherothrombosis is triggered when an unstable atherosclerotic lesion is ruptured, leading to platelet activation and thrombus formation. Inflammatory mediators are responsible for lesion instability leading to rupture, and in recent years atherothrombosis and its underlying condition of atherosclerosis have come to be recognized as manifestations of inflammatory disease. Inflammatory mediators may therefore serve as early markers of atherothrombosis. Measurement of early markers may be used to predict future ischemic events and improve risk stratification in patients following diagnosis of atherothrombotic disease. In addition, detection of such markers may help to optimize the use of current therapies to manage atherothrombosis. Molecules that may serve as early markers of atherothrombotic disease include C-reactive protein, CD40 ligand, myeloperoxidase, pregnancy-associated plasma protein and plasminogen activator inhibitor-1. Early indications are that levels of these markers are influenced by therapies currently in use in the treatment of atherothrombotic conditions, including antiplatelet agents. Ongoing studies will provide further insight into routine assessment of inflammatory markers as a guide to the management of patients with atherothrombosis. PMID:16961584

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

    PubMed Central

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

    2014-01-01

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

  14. 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

  15. 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

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

    PubMed

    Palmer, Alan M

    2010-11-01

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

  17. Intoxication by intraperitoneal injection or oral gavage equally potentiates postburn organ damage and inflammation.

    PubMed

    Chen, Michael M; Palmer, Jessica L; Ippolito, Jill A; Curtis, Brenda J; Choudhry, Mashkoor A; Kovacs, Elizabeth J

    2013-01-01

    The increasing prevalence of binge drinking and its association with trauma necessitate accurate animal models to examine the impact of intoxication on the response and outcome to injuries such as burn. While much research has focused on the effect of alcohol dose and duration on the subsequent inflammatory parameters following burn, little evidence exists on the effect of the route of alcohol administration. We examined the degree to which intoxication before burn injury causes systemic inflammation when ethanol is given by intraperitoneal (i.p.) injection or oral gavage. We found that intoxication potentiates postburn damage in the ileum, liver, and lungs of mice to an equivalent extent when either ethanol administration route is used. We also found a similar hematologic response and levels of circulating interleukin-6 (IL-6) when either ethanol paradigm achieved intoxication before burn. Furthermore, both i.p. and gavage resulted in similar blood alcohol concentrations at all time points tested. Overall, our data show an equal inflammatory response to burn injury when intoxication is achieved by either i.p. injection or oral gavage, suggesting that findings from studies using either ethanol paradigm are directly comparable. PMID:24379525

  18. Identification of serum monocyte chemoattractant protein-1 and prolactin as potential tumor markers in hepatocellular carcinoma.

    PubMed

    Wang, Who-Whong; Ang, Soo Fan; Kumar, Rajneesh; Heah, Charmain; Utama, Andi; Tania, Navessa Padma; Li, Huihua; Tan, Sze Huey; Poo, Desmond; Choo, Su Pin; Chow, Wan Cheng; Tan, Chee Kiat; Toh, Han Chong

    2013-01-01

    Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV) carrier samples from the Singapore General Hospital (SGH) using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA) array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group)), confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers) by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC) analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC) indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974) had significantly superior discriminative ability than AFP alone (AUC, 0.942; p<0.001). In conclusion, prolactin and MCP-1 are overexpressed in HCC and are conveniently quantifiable in patients' sera by ELISA. MCP-1 appears to be a promising complementary biomarker for HCC diagnosis and this MCP-1+AFP model should be further evaluated as potential

  19. Quantification and Application of Potential Epigenetic Markers in Maternal Plasma of Pregnancies with Hypertensive Disorders

    PubMed Central

    Kim, Hyun Jin; Kim, Shin Young; Lim, Ji Hyae; Kwak, Dong Wook; Park, So Yeon; Ryu, Hyun Mee

    2015-01-01

    The aim of this study was to evaluate quantitative aberrations of novel fetal-specific epigenetic markers in maternal plasma of pregnancies with hypertensive disorders. We compared the concentrations of DSCR3, RASSF1A, and SRY as cell-free fetal DNA markers in 188 normal pregnancies, 16 pregnancies with early-onset preeclampsia (EO-PE), 47 pregnancies with late-onset preeclampsia (LO-PE), and 29 pregnancies with gestational hypertension (GH). The concentrations of all markers were significantly correlated with gestational age (p < 0.001 for all). Strong positive correlations were also observed between DSCR3 and SRY (r = 0.471, p < 0.001), as well as between RASSF1A and SRY (r = 0.326, p = 0.015) and between DSCR3 and RASSF1A (r = 0.673, p < 0.001). The concentrations of DSCR3 and RASSF1A in the EO-PE were significantly higher at 24–32 weeks and onwards (p < 0.05 for both). In the LO-PE, DSCR3 and RASSF1A concentrations were significantly higher only at 33–41 weeks compared with the controls. The concentrations of all markers in the GH group were not significantly different from those in the control group. This study is the first demonstration that DSCR3 is a novel epigenetic marker that can be an alternative to the RASSF1A for the prediction of EO-PE. PMID:26694356

  20. Testing the potential of a ribosomal 16S marker for DNA metabarcoding of insects.

    PubMed

    Elbrecht, Vasco; Taberlet, Pierre; Dejean, Tony; Valentini, Alice; Usseglio-Polatera, Philippe; Beisel, Jean-Nicolas; Coissac, Eric; Boyer, Frederic; Leese, Florian

    2016-01-01

    Cytochrome c oxidase I (COI) is a powerful marker for DNA barcoding of animals, with good taxonomic resolution and a large reference database. However, when used for DNA metabarcoding, estimation of taxa abundances and species detection are limited due to primer bias caused by highly variable primer binding sites across the COI gene. Therefore, we explored the ability of the 16S ribosomal DNA gene as an alternative metabarcoding marker for species level assessments. Ten bulk samples, each containing equal amounts of tissue from 52 freshwater invertebrate taxa, were sequenced with the Illumina NextSeq 500 system. The 16S primers amplified three more insect species than the Folmer COI primers and amplified more equally, probably due to decreased primer bias. Estimation of biomass might be less biased with 16S than with COI, although variation in read abundances of two orders of magnitudes is still observed. According to these results, the marker choice depends on the scientific question. If the goal is to obtain a taxonomic identification at the species level, then COI is more appropriate due to established reference databases and known taxonomic resolution of this marker, knowing that a greater proportion of insects will be missed using COI Folmer primers. If the goal is to obtain a more comprehensive survey the 16S marker, which requires building a local reference database, or optimised degenerated COI primers could be more appropriate. PMID:27114891

  1. Testing the potential of a ribosomal 16S marker for DNA metabarcoding of insects

    PubMed Central

    Elbrecht, Vasco; Taberlet, Pierre; Dejean, Tony; Valentini, Alice; Usseglio-Polatera, Philippe; Beisel, Jean-Nicolas; Coissac, Eric; Boyer, Frederic

    2016-01-01

    Cytochrome c oxidase I (COI) is a powerful marker for DNA barcoding of animals, with good taxonomic resolution and a large reference database. However, when used for DNA metabarcoding, estimation of taxa abundances and species detection are limited due to primer bias caused by highly variable primer binding sites across the COI gene. Therefore, we explored the ability of the 16S ribosomal DNA gene as an alternative metabarcoding marker for species level assessments. Ten bulk samples, each containing equal amounts of tissue from 52 freshwater invertebrate taxa, were sequenced with the Illumina NextSeq 500 system. The 16S primers amplified three more insect species than the Folmer COI primers and amplified more equally, probably due to decreased primer bias. Estimation of biomass might be less biased with 16S than with COI, although variation in read abundances of two orders of magnitudes is still observed. According to these results, the marker choice depends on the scientific question. If the goal is to obtain a taxonomic identification at the species level, then COI is more appropriate due to established reference databases and known taxonomic resolution of this marker, knowing that a greater proportion of insects will be missed using COI Folmer primers. If the goal is to obtain a more comprehensive survey the 16S marker, which requires building a local reference database, or optimised degenerated COI primers could be more appropriate. PMID:27114891

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

    PubMed Central

    Faden, Asmaa A.

    2016-01-01

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

  3. 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

  4. 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

  5. Phylogenetic analysis of multiple FISH markers in oral tongue squamous cell carcinoma suggests that a diverse distribution of copy number changes is associated with poor prognosis.

    PubMed

    Wangsa, Darawalee; Chowdhury, Salim Akhter; Ryott, Michael; Gertz, E Michael; Elmberger, Göran; Auer, Gert; Åvall Lundqvist, Elisabeth; Küffer, Stefan; Ströbel, Philipp; Schäffer, Alejandro A; Schwartz, Russell; Munck-Wikland, Eva; Ried, Thomas; Heselmeyer-Haddad, Kerstin

    2016-01-01

    Oral tongue squamous cell carcinoma (OTSCC) is associated with poor prognosis. To improve prognostication, we analyzed four gene probes (TERC, CCND1, EGFR and TP53) and the centromere probe CEP4 as a marker of chromosomal instability, using fluorescence in situ hybridization (FISH) in single cells from the tumors of sixty-five OTSCC patients (Stage I, n = 15; Stage II, n = 30; Stage III, n = 7; Stage IV, n = 13). Unsupervised hierarchical clustering of the FISH data distinguished three clusters related to smoking status. Copy number increases of all five markers were found to be correlated to non-smoking habits, while smokers in this cohort had low-level copy number gains. Using the phylogenetic modeling software FISHtrees, we constructed models of tumor progression for each patient based on the four gene probes. Then, we derived test statistics on the models that are significant predictors of disease-free and overall survival, independent of tumor stage and smoking status in multivariate analysis. The patients whose tumors were modeled as progressing by a more diverse distribution of copy number changes across the four genes have poorer prognosis. This is consistent with the view that multiple genetic pathways need to become deregulated in order for cancer to progress. PMID:26175310

  6. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in comparison to one containing levonorgestrel and ethinylestradiol on markers of endocrine function

    PubMed Central

    Ågren, Ulla M; Anttilat, Marjatta; Mäenpää-Liukko, Kristiina; Rantala, Maija-Liisa; Rautiainen, Hilkka; Sommer, Werner F; Mommers, Ellen

    2011-01-01

    Objectives To compare the effects of two monophasic combined oral contraceptives, containing either nomegestrol acetate/17β-oestradiol (NOMAC/E2) or levonorgestrel/ ethinylestradiol (LNG/EE) on endocrine function, androgens, and sex hormone-binding globulin (SHBG). Methods Randomised, open-label, multi-centre trial involving 121 healthy women, aged 18-50 years old. Participants received NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen (n = 60) or LNG/EE (150 μg/30 μg) in a 21/7-day regimen (n = 61) for six cycles. The primary outcome was the change from baseline to cycle 6 in markers of adrenal and thyroid function, androgens, and SHBG. Results Total cortisol, corticosteroid-binding globulin (CBG), and thyroxine-binding globulin (TBG) increased from baseline in both groups, with significantly greater increases in the LNG/EE group. No relevant changes from baseline or differences between the groups were observed for thyroid-stimulating hormone (TSH) and free thyroxine (T4). Androgens and androgen precursors decreased from baseline in both groups, with significantly greater decreases in the LNG/EE group (except for free testosterone). A greater increase in SHBG was observed with NOMAC/E2 than with LNG/EE. Conclusions NOMAC/E2 has significantly less influence on markers of adrenal and thyroid function and androgens than LNG/EE. The clinical relevance of these findings requires further study. PMID:21942708

  7. Phylogenetic Analysis of Multiple FISH Markers in Oral Tongue Squamous Cell Carcinoma Suggests that a Diverse Distribution of Copy Number Changes Is Associated with Poor Prognosis

    PubMed Central

    Wangsa, Darawalee; Chowdhury, Salim Akhter; Ryott, Michael; Gertz, E. Michael; Elmberger, Göran; Auer, Gert; Lundqvist, Elisabeth Åvall; Küffer, Stefan; Ströbel, Philipp; Schäffer, Alejandro A.; Schwartz, Russell; Munck-Wikland, Eva; Ried, Thomas; Heselmeyer-Haddad, Kerstin

    2016-01-01

    Oral tongue squamous cell carcinoma (OTSCC) is associated with poor prognosis. To improve prognostication, we analyzed four gene probes (TERC, CCND1, EGFR, and TP53) and the centromere probe CEP4 as a marker of chromosomal instability, using fluorescence in situ hybridization (FISH) in single cells from the tumors of sixty-five OTSCC patients (Stage I, n=15; Stage II, n=30; Stage III, n=7; Stage IV, n=13). Unsupervised hierarchical clustering of the FISH data distinguished three clusters related to smoking status. Copy number increases of all five markers were found to be correlated to non-smoking habits, while smokers in this cohort had low-level copy number gains. Using the phylogenetic modeling software FISHtrees, we constructed models of tumor progression for each patient based on the four gene probes. Then, we derived test statistics on the models that are significant predictors of disease-free and overall survival, independent of tumor stage and smoking status in multivariate analysis. The patients whose tumors were modeled as progressing by a more diverse distribution of copy number changes across the four genes have poorer prognosis. This is consistent with the view that multiple genetic pathways need to become deregulated in order for cancer to progress. PMID:26175310

  8. Identification and evaluation of potential forensic marker proteins in vaginal fluid by liquid chromatography/mass spectrometry.

    PubMed

    Igoh, Akihisa; Doi, Yusuke; Sakurada, Koichi

    2015-09-01

    Vaginal fluid is one of the most common body fluids found at crime scenes. Discriminating vaginal fluid from other body fluids is important in forensic science; however, few potential protein markers have been reported to date. Proteomic methods for identifying protein markers have gained attention, although few reports have applied this technology to forensic protein markers. Therefore, to identify characteristic vaginal proteins, we examined various body fluids (nasal secretions, saliva, urine, semen, vaginal fluids, and sweat) using liquid chromatography/electrospray ionization time-of-flight mass spectrometry and peptide mass fingerprinting. We identified three components (average molecular mass values 17,237 ± 2, 18,063 ± 2, and 15,075 ± 1) detectable only in vaginal samples: two human small proline-rich protein 3 (SPRR3) isoforms and a human fatty acid-binding protein 5 (FABP5) with an acetylated (+42) N-terminal region lacking the initiator methionine residue (-131). Using ELISA, these yielded markedly high average values in vaginal fluids. The mass spectra of these proteins were not detected in infant saliva but were detected in the vaginal fluid throughout the menstrual cycle. The results of forensic analysis (detection limit, mixed body fluid samples, casework samples, and blind samples) suggest that these proteins are potential forensic markers. In conclusion, high SPRR3 and FABP5 expression levels, which may be used as potential markers for vaginal fluid identification in forensic science, were detected in vaginal fluids from healthy adults. PMID:26164306

  9. Elevated S100A9 expression in tumor stroma functions as an early recurrence marker for early-stage oral cancer patients through increased tumor cell invasion, angiogenesis, macrophage recruitment and interleukin-6 production

    PubMed Central

    Fang, Wei-Yu; Chen, Yi-Wen; Hsiao, Jenn-Ren; Liu, Chiang-Shin; Kuo, Yi-Zih; Wang, Yi-Ching; Chang, Kung-Chao; Tsai, Sen-Tien; Chang, Mei-Zhu; Lin, Siao-Han; Wu, Li-Wha

    2015-01-01

    S100A9 is a calcium-binding protein with two EF-hands and frequently deregulated in several cancer types, however, with no clear role in oral cancer. In this report, the expression of S100A9 in cancer and adjacent tissues from 79 early-stage oral cancer patients was detected by immunohistochemical staining. Although S100A9 protein was present in both tumor and stromal cells, only the early-stage oral cancer patients with high stromal expression had reduced recurrence-free survival. High stromal S100A9 expression was also significantly associated with non-well differentiation and recurrence. In addition to increasing cell migration and invasion, ectopic S100A9 expression in tumor cells promoted xenograft tumorigenesis as well as the dominant expression of myeloid cell markers and pro-inflammatory IL-6. The expression of S100A9 in one stromal component, monocytes, stimulated the aggressiveness of co-cultured oral cancer cells. We also detected the elevation of serum S100A9 levels in early-stage oral cancer patients of a separate cohort of 73 oral cancer patients. The release of S100A9 protein into extracellular milieu enhanced tumor cell invasion, transendothelial monocyte migration and angiogenic activity. S100A9-mediated release of IL-6 requires the crosstalk of tumor cells with monocytes through the activation of NF-κB and STAT-3. Early-stage oral cancer patients with both high S100A9 expression and high CD68+ immune infiltrates in stroma had shortest recurrence-free survival, suggesting the use of both S100A9 and CD68 as poor prognostic markers for oral cancer. Together, both intracellular and extracellular S100A9 exerts a tumor-promoting action through the activation of oral cancer cells and their associated stroma in oral carcinogenesis. PMID:26315114

  10. Identification of Apolipoprotein C-I as a Potential Wilms’ Tumor Marker after Excluding Inflammatory Factors

    PubMed Central

    Zhang, Junjie; Guo, Fei; Wang, Lei; Zhao, Wei; Zhang, Da; Yang, Heying; Yu, Jiekai; Niu, Lili; Yang, Fuquan; Zheng, Shu; Wang, Jiaxiang

    2014-01-01

    Wilms’ tumor is one of the most common malignant tumors observed in children, and its early diagnosis is important for late-stage treatment and prognosis. We previously screened and identified protein markers for Wilms’ tumor; however, these markers lacked specificity, and some were associated with inflammation. In the current study, serum samples from children with Wilms’ tumors were compared with those of healthy controls and patients with systemic inflammatory response syndrome (SIRS). After exclusion of factors associated with inflammation, specific protein markers for Wilms’ tumors were identified. After comparing the protein peak values obtained from all three groups, a protein with a m/z of 6438 Da was specified. Purification and identification of the target protein using high-pressure liquid chromatography (HPLC) and two-dimensional liquid chromatography-linearion trap mass spectrometry(2D-LC-LTQ-MS) mass spectrometry, respectively, revealed that it was apolipoprotein C-I (APO C-I). Thus, APO C-I is a specific protein marker for Wilms’ tumor. PMID:25222555

  11. Discovery and Characterization of Proteins Associated with Aflatoxin-Resistance: Evaluating Their Potential as Breeding Markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Host resistance has become a viable approach to eliminating aflatoxin contamination of maize since the discovery of several maize lines with natural resistance. However, to derive commercial benefit from this resistance and develop lines that can aid growers, markers need to be identified to facilit...

  12. Geriatric forensics - Part 2 “Prevalence of elder abuse and their potential forensic markers among medical and dental patients”

    PubMed Central

    Mattoo, Khurshid A.; Garg, Rishabh; Kumar, Shalabh

    2015-01-01

    Context: This study is a continuation of the earlier studies and has been extended to investigate the potential forensic markers of elder abuse. Aims: To determine the prevalence of elder abuse in various outpatient departments (OPDs). To study the associated parameters related to the abuser and the abused. To determine the existence of potential forensic markers of elder abuse. Settings and Design: The subjects were randomly selected from the medical and the dental OPDs of the university. Materials and Methods: Eight hundred and thirty two elderly subjects in the age range 40-60 years were interviewed using a questionnaire to determine the existence of elder abuse. The subjects were investigated and examined for weight, nutrition and hydration, vital signs, habits, existing visual and auditory capabilities, medications, disclosure of wills/deeds, signs of depression, and documented cleanliness. The mini-mental state examination, the Geriatric Depression Scale, the Clock drawing test, and the Brief Psychiatric Rating Scale were used to determine the potential forensic markers. Statistical Analysis Used: Mean values in percentage were determined by dividing the number of determined subjects by the total number of subjects for that parameter. Results: About 37% in medical and 41% in dental OPDs were found to have suffered from abuse, mostly in the age group 60-70 years. Females received more abuse and a combination of son and daughter-in-law constituted most abusers. Various potential markers of elder abuse and neglect investigated among the elder abuse victims included depression (89%), signs of improper feeding (83%), changes in personal hygiene (69%), need for medical/dental treatment (78%), medication misuse (67%), changes in wills/deeds (26%), decubiti (10%), bruises (17%), skin tears (27%), and confusion (23%). Conclusions: Elder abuse exists in one or more forms in both medical and dental OPDs among both males and females in all age groups. PMID:26816460

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  15. Comparison of Breast Cancer to Healthy Control Tissue Discovers Novel Markers with Potential for Prognosis and Early Detection

    PubMed Central

    Schummer, Michèl; Green, Ann; Beatty, J. David; Karlan, Beth Y.; Karlan, Scott; Gross, Jenny; Thornton, Sean; McIntosh, Martin; Urban, Nicole

    2010-01-01

    This study was initiated to identify biomarkers with potential value for the early detection of poor-outcome breast cancer. Two sets of well-characterized tissues were utilized: one from breast cancer patients with favorable vs. poor outcome and the other from healthy women undergoing reduction mammaplasty. Over 46 differentially expressed genes were identified from a large list of potential targets by a) mining publicly available expression data (identifying 134 genes for quantitative PCR) and b) utilizing a commercial PCR array. Three genes show elevated expression in cancers with poor outcome and low expression in all other tissues, warranting further investigation as potential blood markers for early detection of cancers with poor outcome. Twelve genes showed lower expression in cancers with poor outcome than in cancers with favorable outcome but no differential expression between aggressive cancers and most healthy controls. These genes are more likely to be useful as prognostic tissue markers than as serum markers for early detection of aggressive disease. As a secondary finding was that, when histologically normal breast tissue was removed from a distant site in a breast with cancer, 7 of 38 specimens displayed a cancer-like expression profile, while the remaining 31 were genetically similar to the reduction mammaplasty control group. This finding suggests that some regions of ipsilateral histologically ‘normal’ breast tissue are predisposed to becoming malignant and that normal-appearing tissue with malignant signature might warrant treatment to prevent new primary tumors. PMID:20161755

  16. DNA methylome profiling of maternal peripheral blood and placentas reveal potential fetal DNA markers for non-invasive prenatal testing.

    PubMed

    Xiang, Yuqian; Zhang, Junyu; Li, Qiaoli; Zhou, Xinyao; Wang, Teng; Xu, Mingqing; Xia, Shihui; Xing, Qinghe; Wang, Lei; He, Lin; Zhao, Xinzhi

    2014-09-01

    Utilizing epigenetic (DNA methylation) differences to differentiate between maternal peripheral blood (PBL) and fetal (placental) DNA has been a promising strategy for non-invasive prenatal testing (NIPT). However, the differentially methylated regions (DMRs) have yet to be fully ascertained. In the present study, we performed genome-wide comparative methylome analysis between maternal PBL and placental DNA from pregnancies of first trimester by methylated DNA immunoprecipitation-sequencing (MeDIP-Seq) and Infinium HumanMethylation450 BeadChip assays. A total of 36 931 DMRs and 45 804 differentially methylated sites (DMSs) covering the whole genome, exclusive of the Y chromosome, were identified via MeDIP-Seq and Infinium 450k array, respectively, of which 3759 sites in 2188 regions were confirmed by both methods. Not only did we find the previously reported potential fetal DNA markers in our identified DMRs/DMSs but also we verified fully the identified DMRs/DMSs in the validation round by MassARRAY EpiTYPER. The screened potential fetal DNA markers may be used for NIPT on aneuploidies and other chromosomal diseases, such as cri du chat syndrome and velo-cardio-facial syndrome. In addition, these potential markers may have application in the early diagnosis of placental dysfunction, such as pre-eclampsia. PMID:24996894

  17. Analysis of the excreted JC virus strains and their potential oral transmission.

    PubMed

    Bofill-Mas, Sílvia; Clemente-Casares, Pilar; Major, Eugene O; Curfman, Blanche; Girones, Rosina

    2003-08-01

    JC virus (JCV) particles have been detected in urban sewage of divergent geographical areas. In this study, the authors evaluate the genetic characteristics and the infective capabilities of JCV strains in relation to the potential oral transmission of JCV in the population. JCV strains excreted in urine and detected in sewage have been described as presenting archetypal structure of the regulatory region of the viral genome. The regulatory region of JCV viral particles detected in two urban sewage samples have been cloned and characterized. From a total of 40 clones tested, 39 presented archetypal-like regulatory regions, whereas 1 of the clones analyzed presented a tandem repeated structure. Archetypal strains present in the urine of a pregnant woman were able to infect SVG cells, producing infectious virions, as demonstrated by confirmative cell culture, electron microscopy, and in situ DNA hybridization. This is the first description of archetypal JCV productive infection of SVG cells. SVG cells were also successfully infected with Mad-4 JCV viral particles subjected to pH 3 for 1 h at 37 degrees C and to 10 microg/ml of trypsin in the same conditions. A decrease in the viral progeny production was observed when Mad-4 was subjected to acidic pH. Mad-4 did not produce any detectable infection in the enteric cell line CaCo-2. The oral route could represent a significant route of transmission of JCV infections because JCV virions have demonstrated relative resistance in the environment and to some of the conditions present in the gastrointestinal tract. The archetypal strains commonly detected in the environment may be implicated in the transmission of JCV among the population. Sporadic infection with strains presenting tandem repeated structures may have implications in pathogenicity. PMID:12907394

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

    PubMed

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

    2007-01-01

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

  19. The effect of past use of oral contraceptive on bone mineral density, bone biochemical markers and muscle strength in healthy pre and post menopausal women

    PubMed Central

    Allali, Fadoua; El Mansouri, Laila; Abourazzak, Fatima zohra; Ichchou, Linda; Khazzani, Hamza; Bennani, Loubna; Abouqal, Redouane; Hajjaj-Hassouni, Najia

    2009-01-01

    Background during adulthood, most studies have reported that oral contraceptive (OC) pills had neutral, or possibly beneficial effect on bone health. We proposed this study of pre and post menopausal women assessing BMD, bone biochemical markers and physical performance among OC past users and comparable women who have never use Ocs. Methods A cross-sectional study comparing the bone density, bone biochemical markers (osteocalcin, CTX) and three measures to assess physical performance: timed get-up-and-go test "TGUG", five-times-sit-to-stand test "5 TSTS" and 8-feet speed walk "8 FSW" of users and never users OC. We were recruited 210 women who used OC for at least 2 years with that of 200 nonusers was carried out in pre and postmenopausal women (24-86 years). Results when analysing the whole population, BMD and biochemical markers values were similar for Ocs past users and control subjects. However when analysing the subgroup of premenopausal women, there was a statistically significant difference between users and never-users in osteocalcin (15,5 ± 7 ng/ml vs 21,6 ± 9 ng/ml; p = 0,003) and CTX (0,30 ± 0,1 ng/ml vs 0,41 ± 0,2 ng/ml; p = 0,025). This difference persisted after adjustment for age, BMI, age at menarche and number of pregnancies. In contrast, in post menopausal women, there was no difference in bone biochemical markers between OC users and the control. On the other hand OC past users had a significant greater performance than did the never users group. And when analysing the physical performance tests by quartile OC duration we found a significant negative association between the three tests and the use of OC more than 10 years. Conclusion the funding show no evidence of a significant difference in BMD between Ocs users and never user control groups, a decrease in bone turn over in OC pre menopausal users and a greater physical performances in patients who used OC up than 10 years. PMID:19887010

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

    PubMed

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

    2014-01-01

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

  1. 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

  2. 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

  3. 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

  4. Hypoxia in human colorectal adenocarcinoma: Comparison between extrinsic and potential intrinsic hypoxia markers

    SciTech Connect

    Goethals, Laurence; Debucquoy, Annelies; Perneel, Christiaan; Geboes, Karel; Ectors, Nadine; De Schutter, Harlinde; Penninckx, Freddy; McBride, William H.; Begg, Adrian C.; Haustermans, Karin M. . E-mail: karin.haustermans@uzleuven.be

    2006-05-01

    Purpose: To detect and quantify hypoxia in colorectal adenocarcinomas by use of pimonidazole and iododeoxyuridine (IdUrd) as extrinsic markers and carbonic anhydrase IX (CA IX), microvessel density (MVD), epidermal growth-factor receptor (EGFR), and vascular endothelial growth factor (VEGF) as intrinsic markers of hypoxia. Methods and Material: Twenty patients with an adenocarcinoma of the left colon and rectum treated by primary surgery were injected with pimonidazole and IdUrd. Serial sections of tumor biopsies were single stained for VEGF, EGFR, Ki67, and double stained for blood vessels in combination with either pimonidazole, IdUrd, or CA IX. Percentage of expression was scored as well as colocalization of pimonidazole with CA IX. Results: The median percentage of hypoxia, as judged by pimonidazole staining, was 16.7% (range, 0-52.4%). The expression of pimonidazole correlated inversely with the total MVD and endothelial cord MVD (R = -0.55, p = 0.01; R = -0.47, p = 0.04). Good colocalization was found between pimonidazole and CA IX in only 30% of tumors, with no correlation overall between pimonidazole and CA IX, VEGF, or EGFR or between the different intrinsic markers. Cells around some vessels (0.08-11%) were negative for IdUrd but positive for Ki 67, which indicated their lack of perfusion at the time of injection. Conclusion: Chronic and acute hypoxic regions are present in colorectal tumors, as shown by pimonidazole and IdUrd staining. Only in a minority of tumors did an association exist between the areas stained by pimonidazole and those positive for CA IX. Pimonidazole also did not correlate with expression of other putative intrinsic hypoxia markers (VEGF, EGFR)

  5. Identification of innovative potential quality markers in rocket and melon fresh-cut produce.

    PubMed

    Cavaiuolo, Marina; Cocetta, Giacomo; Bulgari, Roberta; Spinardi, Anna; Ferrante, Antonio

    2015-12-01

    Ready-to-eat fresh cut produce are exposed to pre- and postharvest abiotic stresses during the production chain. Our work aimed to identify stress responsive genes as new molecular markers of quality that can be widely applied to leaves and fruits and easily determined at any stage of the production chain. Stress responsive genes associated with quality losses were isolated in rocket and melon fresh-cut produce and their expression levels analyzed by quantitative real time PCR (qRT-PCR) at different time points after harvest at 20 °C and 4 °C. qRT-PCR results were supported by correlation analysis with physiological and biochemical determinations evaluated at the same conditions such as chlorophyll a fluorescence indices, total, reducing sugars, sucrose, ethylene, ascorbic acid, lipid peroxidation and reactive oxygen species. In both species the putative molecular markers increased their expression soon after harvest suggesting a possible use as novel and objective quality markers of fresh-cut produces. PMID:26041186

  6. Anthocyanin production as a potential visual selection marker during plant transformation.

    PubMed

    Kortstee, A J; Khan, S A; Helderman, C; Trindade, L M; Wu, Y; Visser, R G F; Brendolise, C; Allan, A; Schouten, H J; Jacobsen, E

    2011-12-01

    A mutant allele of the transcription factor gene MYB10 from apple induces anthocyanin production throughout the plant. This gene, including its upstream promoter, gene coding region and terminator sequence, was introduced into apple, strawberry and potato plants to determine whether it could be used as a visible selectable marker for plant transformation as an alternative to chemically selectable markers, such as kanamycin resistance. After transformation, red coloured calli, red shoots and red well-growing plants were scored. Red and green shoots were harvested from apple explants and examined for the presence of the MYB10 gene by PCR analysis. Red shoots of apple explants always contained the MYB10 gene but not all MYB10 containing shoots were red. Strawberry plants transformed with the MYB10 gene showed anthocyanin accumulation in leaves and roots. No visible accumulation of anthocyanin could be observed in potato plants grown in vitro, even the ones carrying the MYB10 gene. However, acid methanol extracts of potato shoots or roots carrying the MYB10 gene contained up to four times higher anthocyanin content than control plants. Therefore anthocyanin production as result of the apple MYB10 gene can be used as a selectable marker for apple, strawberry and potato transformation, replacing kanamycin resistance. PMID:21340526

  7. Effects of a single, high oral dose of 25-hydroxycholecalciferol on the mineral metabolism markers in hemodialysis patients.

    PubMed

    Merino, Jose Luis; Teruel, Jose Luis; Fernández-Lucas, Milagros; Villafruela, Juan José; Bueno, Blanca; Gomis, Antonio; Paraíso, Vicente; Quereda, Carlos

    2015-06-01

    Vitamin D deficiency is common in dialysis patients with chronic kidney disease. Low levels have been associated with increased cardiovascular risk and mortality. We evaluated the administration of a high, single oral dose of 25-OH cholecalciferol (3 mg of Hidroferol, 180 000 IU) in patients on chronic hemodialysis. The 94 chronic hemodialysis patients with vitamin D deficiency 25 (OH)D <30 ng/mL included in the study were randomized into two groups. Follow-up time was 16 weeks. Neither the usual treatment for controlling Ca/P levels nor the dialysis bath (calcium of 2.5 mEq/L) were modified. Of the 86 patients who finished the study, 42 were in the treated group and 44 in the control group. An increase in 25(OH)D levels was observed in the treated group that persisted after 16 weeks and was associated with a significant decrease in parathyroid hormone (PTH) levels during the 8 weeks post-treatment. Baseline 1,25(OH)2 D levels of the treated group increased two weeks after treatment (5.9 vs. 21.9 pg/mL, P<0.001) but gradually reduced to 8.4 at week 16. The administration of a single 3 mg dose of 25-OH cholecalciferol seems safe in patients on hemodialysis and maintains sufficient levels of 25(OH)D with a decrease in PTH for 3 months. PMID:25656524

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Harris, K; Mant, J

    2013-01-01

    Aim Anticoagulant prophylaxis with vitamin K antagonists (such as warfarin) is effective in reducing the risk of stroke in patients with atrial fibrillation (AF). New oral anticoagulants have emerged as potential alternatives to traditional oral agents. The purpose of this review was to summarise the effectiveness and safety of rivaroxaban, dabigatran and apixaban in stroke prevention in patients with AF in phase III trials, evaluate their cost-effectiveness and consider the implications for primary care. Methodology A literature search was performed between 2007 and 2012, selecting all phase III trials (ROCKET AF, RE-LY and ARISTOTLE) of new oral anticoagulants and relevant cost–benefit studies. Results Evidence shows that all three agents are at least as effective as warfarin in the prevention of stroke and systemic emboli, with similar safety profiles. Cost–benefit studies of rivaroxaban and dabigatran further confirm their potential use as alternatives to warfarin in clinical practice. These observations may allow stratification of the general practice AF population, to help prioritise which patients may benefit from receiving a new oral anticoagulant. Conclusion The clinical and economic benefits of the new oral anticoagulants, along with appropriate risk stratification, may enable a higher number of patients with AF to receive effective and convenient prophylaxis for stroke prevention. PMID:23621153

  10. High neutrophil-to-lymphocyte ratio is an independent marker of poor disease-specific survival in patients with oral cancer.

    PubMed

    Perisanidis, Christos; Kornek, Gabriela; Pöschl, Paul W; Holzinger, Daniel; Pirklbauer, Katharina; Schopper, Christian; Ewers, Rolf

    2013-03-01

    With growing evidence on the role of inflammation in carcinogenesis, the presence of a systemic inflammatory response has been proposed as having prognostic significance in a wide range of cancers. The aim of the study was to assess the value of pretreatment neutrophil-to-lymphocyte ratio (NLR) in predicting disease-specific survival (DSS) in patients with oral cancer undergoing preoperative chemoradiotherapy. A cohort of 97 patients with locally advanced oral squamous cell carcinoma receiving preoperative chemoradiotherapy was retrospectively examined. The impact of NLR and other potential prognostic factors on DSS was assessed with the Kaplan-Meier method and multivariate Cox regression analysis. Sixty-nine patients had a high pretreatment NLR, with NLR > 1.9 considered as high according to receiver operating characteristic curve analysis. In univariate analysis, high pretreatment NLR (p = 0.018), positive perineural invasion (p < 0.001) and advanced pathologic TNM stage after neoadjuvant therapy (p < 0.001) were predictive of shorter DSS. In multivariate analysis, advanced pathologic TNM stage after neoadjuvant therapy (HR 1.71, 95 % CI 1.17-2.48, p = 0.005), positive perineural invasion (HR 3.67, 95 % CI 1.11-12.13, p = 0.033) and high pretreatment NLR (HR 10.37, 95 % CI 1.28-84.08, p = 0.029) remained independently associated with poor DSS. A high pretreatment NLR is a significant independent predictor of shorter DSS in patients with oral cancer receiving preoperative chemoradiotherapy. PMID:23292862

  11. 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 ...

  12. 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.

  13. Diagnostic values of serum tumor markers Cyfra21-1, SCCAg, ferritin, CEA, CA19-9, and AFP in oral/oropharyngeal squamous cell carcinoma

    PubMed Central

    Yuan, Chuanshu; Yang, Kai; Tang, Hong; Chen, Dan

    2016-01-01

    Background At present, the research on serum tumor markers in the early diagnosis of malignant tumors has aroused widespread concern. The aim of this study was to investigate the diagnostic values of serum tumor markers cytokeratin 19 fragment (Cyfra21-1), squamous cell carcinoma antigen (SCCAg), ferritin, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and α-fetoprotein (AFP) for patients with oral/oropharyngeal squamous carcinoma (OSCC/OPSCC). Methods One hundred and sixty-nine cases of patients with OSCC/OPSCC as the experimental group, 86 cases of oral benign tumor patients as the control group, and 30 cases of healthy people as the normal control group were studied. The levels of serum Cyfra21-1, SCCAg, ferritin, CEA, CA19-9, and AFP were measured using electrochemiluminescence immunoassay. Results The levels of serum Cyfra21-1, SCCAg, ferritin, and CEA in patients with OSCC/OPSCC were significantly higher than those of benign tumor and healthy control group (P<0.05). The levels of CA19-9 and AFP showed no significant difference between patients with OSCC/OPSCC, benign tumor, and healthy group (P>0.05). The level of serum Cyfra21-1 in patients with early OSCC/OPSCC (stage I + II) was significantly higher than that of benign tumor and healthy control group (P<0.05). However, the levels of serum SCCAg, ferritin, CEA, CA19-9, and AFP showed no significant difference between patients with early OSCC/OPSCC, benign tumor, and healthy control group (P>0.05). The levels of serum Cyfra21-1, SCCAg, ferritin, and CEA in the middle-late stage of patients with OSCC/OPSCC (stage III + IV) were significantly higher than those of patients with the early OSCC/OPSCC, benign tumor, and healthy control group (P<0.05). The diagnostic cutoff levels of Cyfra21-1, SCCAg, ferritin, and CEA were 2.17, 0.72, 109.95, and 1.99 ng/mL, respectively. The sensitivities were 60.36%, 73.37%, 81.66%, and 66.27%, respectively. The specificities were 81.03%, 68.10%, 40

  14. Nucleolin identified by comparative mass‑spectra analysis is a potential marker for invasive progression of hepatocellular carcinoma.

    PubMed

    Qian, Bin; Yao, Yusheng; Liu, Yihong; Yan, Maolin; Huang, Ying; Chen, Yanqing

    2014-09-01

    At present, the diagnosis and prognosis of hepatocellular carcinoma (HCC) metastasis remains poor. Recently, a number of proteins associated with the metastasis and invasion of HCC were identified; however, the effective markers require further elucidation. In the current study, a nucleolin expression was observed in MHCC97L and HCCLM9 HCC cell lines, with low and high metastatic potentials respectively, using comparative proteomics. The data indicated that nucleolin expression in the nucleus was significantly higher in HCCLM9 cells, and it primarily influenced the migration of HCC cells in vitro. Thus, to the best of our knowledge this is the first study to hypothesize that nucleolin may be a novel marker for HCC invasive progression. PMID:24927373

  15. 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…

  16. 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

  17. Serum levels of hepatocyte growth factor as a potential tumor marker in patients with malignant melanoma.

    PubMed

    Hügel, Rainer; Muendlein, Axel; Volbeding, Lennart; Drexel, Heinz; Richtig, Erika; Wehkamp, Ulrike; Painsi, Clemes; Lange-Asschenfeldt, Bernhard; Hauschild, Axel; Egberts, Friederike

    2016-08-01

    Serum markers can be important tools for prognostic classification and treatment monitoring in cancer patients. The MAP-kinase pathway, which is upregulated in the majority of melanoma patients, can be activated by hepatocyte-growth factor (HGF) through the proto-oncogene c-MET. The aim of this study was to evaluate the predictive and prognostic value of circulating HGF in terms of treatment outcome and survival compared with a widely established serum marker, protein S-100B, in patients with advanced metastatic melanoma. HGF and S-100B were measured in serum samples of 101 patients with metastatic melanoma (American Joint Committee on Cancer stage IV) before and after treatment and 50 patients with stage I/II melanoma. HGF and S-100B correlated significantly with the stage of disease (P=0.032 and P<0.001, respectively). In stage IV melanoma patients, baseline serum levels of HGF and S-100B were significantly associated with treatment response (P=0.012 and 0.006, respectively). Furthermore, the Cox regression analysis confirmed that serum levels of HGF and S-100B proved to have a significant prognostic impact on progression-free survival (hazard ratio=1.39 and 1.29, respectively) and overall survival (hazard ratio=1.27 and 1.29, respectively) in advanced metastatic melanoma patients. In melanoma patients, serum levels of HGF and S-100B correlate significantly with the stage of disease. In stage IV melanoma, both markers are prognostic factors and correlate significantly with progression-free survival and overall survival. Measurement of serum HGF levels might be a useful additional tool in the management of melanoma patients. PMID:27206057

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

    PubMed

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

    1995-10-01

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

  19. 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

  20. p53 as a prognostic marker associated with the risk of mortality for oral squamous cell carcinoma

    PubMed Central

    Cutilli, Tommaso; Leocata, Pietro; Dolo, Vincenza; Altobelli, Emma

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is often associated with a poor prognosis. The purpose of the present study was to investigate survival and the risk of mortality in OSCC with regard to stage, tumor site and p53 expression. A retrospective study was performed on 150 non-consecutive cases of OSCC that were observed between January 1992 and January 2012, and were selected from a total of 580 patients according to the criteria of the homogeneity of histopathological grading (G2). The medical records were reviewed for 48 cases with disease at stage I [37 males, age 64.7±5.7 years (mean age±standard deviation); 11 females, age 70.0±3.37 years]; 27 cases with stage II (15 males, age 64.5±5.6 years; 12 females, age 69.2±3.9 years); 58 cases with stage IVa (42 males, age 66.9±5.3 years; 16 females, age 64.2±6.5 years); and 17 cases with stage IVb (16 males, age 65.7±5.4 years; 1 female, age 69 years). Monoclonal p53 antibody (clone DO-7) was used to perform the p53 immunohistochemical study. A significant association was found between the site of the tumor and p53 overexpression (P<0.0001). Stage I–II cases showed a higher cumulative probability of a 24-month survival time than stage IVa-IVb cases (P<0.0001). Cheek, floor and soft palate tumors showed a worse prognosis (P<0.0001) and tumors with p53 overexpression >50% showed a poor survival rate (P<0.0001) compared with tumors of the attached gingiva, tongue and retromolar trigone. The findings allowed the quantification of the risk mortality from OSSC with regard to stage, tumor site and the p53 expression pattern of the tumor. Data supported the absolute indications for wide surgical margins (radical surgery) in cases of T1-T2 N0 tumors of the tongue, floor, retromolar trigone and attached gingiva when p53 overexpression is >50% in association with a higher risk of mortality compared with when p53 overexpression is <50%.

  1. Statistical strategies to reveal potential vibrational markers for in vivo analysis by confocal Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Oliveira Mendes, Thiago de; Pinto, Liliane Pereira; Santos, Laurita dos; Tippavajhala, Vamshi Krishna; Téllez Soto, Claudio Alberto; Martin, Airton Abrahão

    2016-07-01

    The analysis of biological systems by spectroscopic techniques involves the evaluation of hundreds to thousands of variables. Hence, different statistical approaches are used to elucidate regions that discriminate classes of samples and to propose new vibrational markers for explaining various phenomena like disease monitoring, mechanisms of action of drugs, food, and so on. However, the technical statistics are not always widely discussed in applied sciences. In this context, this work presents a detailed discussion including the various steps necessary for proper statistical analysis. It includes univariate parametric and nonparametric tests, as well as multivariate unsupervised and supervised approaches. The main objective of this study is to promote proper understanding of the application of various statistical tools in these spectroscopic methods used for the analysis of biological samples. The discussion of these methods is performed on a set of in vivo confocal Raman spectra of human skin analysis that aims to identify skin aging markers. In the Appendix, a complete routine of data analysis is executed in a free software that can be used by the scientific community involved in these studies.

  2. Cytokeratin-17 as a potential marker for squamous cell carcinoma of the larynx.

    PubMed

    Cohen-Kerem, Raanan; Madah, Wahid; Sabo, Edmond; Rahat, Michal A; Greenberg, Elhanan; Elmalah, Irit

    2004-10-01

    To assess cytokeratin-17 (CK17) as an immunohistochemical marker for squamous cell carcinoma of the larynx, we stained 63 tissue samples from 63 consecutive patients who were believed or suspected to have squamous cell carcinoma of the larynx for CK17 and analyzed them by computerized histomorphometry. The mean staining intensity for CK17 was significantly stronger (p < .01) in cancerous cells, dysplasia, and normal epithelium proximal to the tumor than in distal normal epithelium and polyps. The percentage of stained area, within samples taken from a single patient, was significantly higher in malignancy and dysplasia as compared to distal normal epithelium and in malignancy as compared to dysplasia and proximal normal epithelium (p < .001). The integrated optical density was significantly higher in the malignant epithelium, dysplasia, polyps, and proximal normal epithelium than in distal normal epithelium (p < .0001). We conclude that CK17 is a highly sensitive and specific immunohistochemical marker for premalignant and malignant transformation in the larynx. Further investigation is warranted in order to assess the role of CK17 in determining safe resection borders. PMID:15535145

  3. New potential markers of in vitro tomato morphogenesis identified by mRNA differential display.

    PubMed

    Torelli, A; Soragni, E; Bolchi, A; Petrucco, S; Ottonello, S; Branca, C

    1996-12-01

    The identification of plant genes involved in early phases of in vitro morphogenesis can not only contribute to our understanding of the processes underlying growth regulator-controlled determination, but also provide novel markers for evaluating the outcome of in vitro regeneration experiments. To search for such genes and to monitor changes in gene expression accompanying in vitro regeneration, we have adapted the mRNA differential display technique to the comparative analysis of a model system of tomato cotyledons that can be driven selectively toward either shoot or callus formation by means of previously determined growth regulator supplementations. Hormone-independent transcriptional modulation (mainly down-regulation) has been found to be the most common event, indicating that a non-specific reprogramming of gene expression quantitatively predominates during the early phases of in vitro culture. However, cDNA fragments representative of genes that are either down-regulated or induced in a programme-specific manner could also be identified, and two of them (G35, G36) were further characterized. One of these cDNA fragments, G35, corresponds to an mRNA that is down-regulated much earlier in callus- (day 2) than in shoot-determined explants (day 6). The other, G36, identifies an mRNA that is transiently expressed in shoot-determined explants only, well before any macroscopic signs of differentiation become apparent, and thus exhibits typical features of a morphogenetic marker. PMID:8980540

  4. Molecular and immunologic markers of kidney cancer-potential applications in predictive, preventive and personalized medicine.

    PubMed

    Mickley, Amanda; Kovaleva, Olga; Kzhyshkowska, Julia; Gratchev, Alexei

    2015-01-01

    Kidney cancer is one of the deadliest malignancies due to frequent late diagnosis (33 % or renal cell carcinoma are metastatic at diagnosis) and poor treatment options. There are two major subtypes of kidney cancer: renal cell carcinoma (RCC) and renal pelvis carcinoma. The risk factors for RCC, accounting for more than 90 % of all kidney cancers, are smoking, obesity, hypertension, misuse of pain medication, and some genetic diseases. The most common molecular markers of kidney cancer include mutations and epigenetic inactivation of von Hippel-Lindau (VHL) gene, genes of vascular endothelial growth factor (VEGF) pathway, and carbonic anhydrase IX (CIAX). The role of epigenetic pathways, including DNA methylation and chromatin structure remodeling, was also demonstrated. Immunologic properties of RCC enable this type of tumor to escape immune response effectively. An important role in this process is played by tumor-associated macrophages that demonstrate mixed M1/M2 phenotype. In this review, we discuss molecular and cellular aspects for RCC development and current state of knowledge allowing personalized approaches for diagnostics and prognostic prediction of this disease. A set of macrophage markers is suggested for the analysis of the association of macrophage phenotype and disease prognosis. PMID:26500709

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

    PubMed

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

    2014-01-01

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

  6. Single oral acute fluoride exposure causes changes in cardiac expression of oxidant and antioxidant enzymes, apoptotic and necrotic markers in male rats.

    PubMed

    Panneerselvam, Lakshmikanthan; Govindarajan, Vimal; Ameeramja, Jaishabanu; Nair, Harikumaran Raveendran; Perumal, Ekambaram

    2015-12-01

    Several studies have shown that acute fluoride (F(-)) exposure impairs cardiac function, but the molecular mechanism is not clear. In order to study this, male Wistar rats were treated with single oral doses of 45 and 90 mg/kg F(-) for 24 h. A significant accumulation of F(-) was found in the serum and myocardium of experimental rats. F(-) treatment causes myocardial necrosis as evident from increased levels of myocardial troponin I, creatine kinase, lactate dehydrogenase and aspartate transaminase. In addition, F(-) induces myocardial oxidative stress via increased reactive oxygen species, lipid peroxidation, protein carbonyl content and nitrate levels along with decreased in the levels of enzymatic (superoxide dismutase 2, catalase, glutathione peroxidase and glutathione s transferase pi class) and non-enzymatic (reduced glutathione) antioxidants. Notably, F(-) triggers myocardial apoptosis through altered Bax/Bcl2 ratio and increased cytochrome c, caspase 3p20 and terminal deoxynucleotidyl transferase dUTP nick end labeled positive cells. An increased cardiac expression of Nox4 and p38α MAPK in F(-) treated rats indicates the oxidative and apoptotic damage. Moreover, ultra-structural changes, histopathological and luxol fast blue staining demonstrates the degree of myocardial damage at subcellular level. Taken together, these findings reveal that acute F(-) exposure causes cardiac impairment by altering the expression of oxidative stress, apoptosis and necrotic markers. PMID:26455266

  7. HIF-1alpha Expression Profile in Intratumoral and Peritumoral Inflammatory Cells as a Prognostic Marker for Squamous Cell Carcinoma of the Oral Cavity

    PubMed Central

    Mendes, Suzanny Oliveira; dos Santos, Marcelo; Peterle, Gabriela Tonini; Maia, Lucas de Lima; Stur, Elaine; Agostini, Lidiane Pignaton; de Carvalho, Marcos Brasilino; Tajara, Eloiza Helena; Louro, Iúri Drumond; Trivilin, Leonardo Oliveira; da Silva-Conforti, Adriana Madeira Álvares

    2014-01-01

    The HIF-1 transcriptional complex is responsible for controlling transcription of over 100 genes involved in cell hypoxia response. HIF-1alpha subunit is stabilized in hypoxia conditions, creating the HIF-1 nuclear transcription factor. In inflammatory cells, high HIF-1alpha expression induces lymphocytic immunosuppression, decreasing tumoral antigen recognition, which promotes tumor growth. The present work investigated the relationship between HIF-1alpha expression in lymphocytes populating the intratumoral and peritumoral region of 56 patients with oral cancer. Our data indicates a prognostic value for this expression. High HIF-1alpha expression in peritumoral inflammatory cells is significantly related to worse patient outcome, whereas high expression in the intratumoral lymphoid cells correlates with a better prognosis. A risk profile indicating the chance of disease relapse and death was designed based on HIF-1alpha expression in tumoral inflammatory cells, defining low, intermediate and high risks. This risk profile was able to determine that high HIF-1alpha expression in peritumoral cells correlates with worse prognosis, independently of intratumoral expression. Low HIF-1alpha in tumor margins and high expression in the tumor was considered a low risk profile, showing no cases of disease relapse and disease related death. Intermediate risk was associated with low expression in tumor and tumor margins. Our results suggest that HIF-1alpha expression in tumor and peritumoral inflammatory cells may play an important role as prognostic tumor marker. PMID:24416312

  8. Orally active carbapenem antibiotics I. Antibacterial and pharmacokinetic potential of 2-phenyl and 2-thienylcarbapenems.

    PubMed

    Sunagawa, Makoto; Ueda, Yutaka; Okada, Shin-Ichiro; Watanabe, Shoji; Hashizuka, Takahiko; Hori, Seiji; Sasaki, Akira; Eriguchi, Yoshiro; Kanazawa, Katsunori

    2005-12-01

    In order to design orally active carbapenem antibiotics effective against beta-lactam-resistant pathogens, such as penicillin-resistant Streptococcus pneumoniae (PRSP) and beta-lactamase non-producing ampicillin-resistant Haemophilus influenzae (BLNAR), a series of novel 2-phenylcarbapenems and some 2-thienyl derivatives were synthesized and tested for antibacterial activities. These compounds were highly active against PRSP, BLNAR, and major Gram-positive and Gram-negative bacteria that cause community-acquired infections. Their pivaloyloxymethylester-type prodrug exhibited good oral absorption in mice, suggesting that this series of carbapenems were promising as a prototype of novel orally active beta-lactams. PMID:16506696

  9. 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

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

    PubMed Central

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

    2016-01-01

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

  11. Assessment of four molecular markers as potential DNA barcodes for red algae Kappaphycus Doty and Eucheuma J. Agardh (Solieriaceae, Rhodophyta).

    PubMed

    Tan, Ji; Lim, Phaik-Eem; Phang, Siew-Moi; Hong, Dang Diem; Sunarpi, H; Hurtado, Anicia Q

    2012-01-01

    DNA barcoding has been a major advancement in the field of taxonomy, seeing much effort put into the barcoding of wide taxa of organisms, macro and microalgae included. The mitochondrial-encoded cox1 and plastid-encoded rbcL has been proposed as potential DNA barcodes for rhodophytes, but are yet to be tested on the commercially important carrageenophytes Kappaphycus and Eucheuma. This study gauges the effectiveness of four markers, namely the mitochondrial cox1, cox2, cox2-3 spacer and the plastid rbcL in DNA barcoding on selected Kappaphycus and Eucheuma from Southeast Asia. Marker assessments were performed using established distance and tree-based identification criteria from earlier studies. Barcoding patterns on a larger scale were simulated by empirically testing on the commonly used cox2-3 spacer. The phylogeny of these rhodophytes was also briefly described. In this study, the cox2 marker which satisfies the prerequisites of DNA barcodes was found to exhibit moderately high interspecific divergences with no intraspecific variations, thus a promising marker for the DNA barcoding of Kappaphycus and Eucheuma. However, the already extensively used cox2-3 spacer was deemed to be in overall more appropriate as a DNA barcode for these two genera. On a wider scale, cox1 and rbcL were still better DNA barcodes across the rhodophyte taxa when practicality and cost-efficiency were taken into account. The phylogeny of Kappaphycus and Eucheuma were generally similar to those earlier reported. Still, the application of DNA barcoding has demonstrated our relatively poor taxonomic comprehension of these seaweeds, thus suggesting more in-depth efforts in taxonomic restructuring as well as establishment. PMID:23285223

  12. Assessment of Four Molecular Markers as Potential DNA Barcodes for Red Algae Kappaphycus Doty and Eucheuma J. Agardh (Solieriaceae, Rhodophyta)

    PubMed Central

    Tan, Ji; Lim, Phaik-Eem; Phang, Siew-Moi; Hong, Dang Diem; Sunarpi, H.; Hurtado, Anicia Q.

    2012-01-01

    DNA barcoding has been a major advancement in the field of taxonomy, seeing much effort put into the barcoding of wide taxa of organisms, macro and microalgae included. The mitochondrial-encoded cox1 and plastid-encoded rbcL has been proposed as potential DNA barcodes for rhodophytes, but are yet to be tested on the commercially important carrageenophytes Kappaphycus and Eucheuma. This study gauges the effectiveness of four markers, namely the mitochondrial cox1, cox2, cox2-3 spacer and the plastid rbcL in DNA barcoding on selected Kappaphycus and Eucheuma from Southeast Asia. Marker assessments were performed using established distance and tree-based identification criteria from earlier studies. Barcoding patterns on a larger scale were simulated by empirically testing on the commonly used cox2-3 spacer. The phylogeny of these rhodophytes was also briefly described. In this study, the cox2 marker which satisfies the prerequisites of DNA barcodes was found to exhibit moderately high interspecific divergences with no intraspecific variations, thus a promising marker for the DNA barcoding of Kappaphycus and Eucheuma. However, the already extensively used cox2-3 spacer was deemed to be in overall more appropriate as a DNA barcode for these two genera. On a wider scale, cox1 and rbcL were still better DNA barcodes across the rhodophyte taxa when practicality and cost-efficiency were taken into account. The phylogeny of Kappaphycus and Eucheuma were generally similar to those earlier reported. Still, the application of DNA barcoding has demonstrated our relatively poor taxonomic comprehension of these seaweeds, thus suggesting more in-depth efforts in taxonomic restructuring as well as establishment. PMID:23285223

  13. Is poor oral health a risk marker for incident cardiovascular disease hospitalisation and all-cause mortality? Findings from 172 630 participants from the prospective 45 and Up Study

    PubMed Central

    Joshy, Grace; Arora, Manish; Korda, Rosemary J; Chalmers, John; Banks, Emily

    2016-01-01

    Objective To investigate the relationship between oral health and incident hospitalisation for ischaemic heart disease (IHD), heart failure (HF), ischaemic stroke and peripheral vascular disease (PVD) and all-cause mortality. Design Prospective population-based study of Australian men and women aged 45 years or older, who were recruited to the 45 and Up Study between January 2006 and April 2009; baseline questionnaire data were linked to hospitalisations and deaths up to December 2011. Study exposures include tooth loss and self-rated health of teeth and gums at baseline. Setting New South Wales, Australia. Participants Individuals aged 45–75 years, excluding those with a history of cancer/cardiovascular disease (CVD) at baseline; n=172 630. Primary outcomes Incident hospitalisation for IHD, HF, ischaemic stroke and PVD and all-cause mortality. Results During a median follow-up of 3.9 years, 3239 incident hospitalisations for IHD, 212 for HF, 283 for ischaemic stroke and 359 for PVD, and 1908 deaths, were observed. Cox proportional hazards models examined the relationship between oral health indicators and incident hospitalisation for CVD and all-cause mortality, adjusting for potential confounding factors. All-cause mortality and incident CVD hospitalisation risk increased significantly with increasing tooth loss for all outcomes except ischaemic stroke (ptrend<0.05). In those reporting no teeth versus ≥20 teeth left, risks were increased for HF (HR, 95% CI 1.97, 1.27 to 3.07), PVD (2.53, 1.81 to 3.52) and all-cause mortality (1.60, 1.37 to 1.87). The risk of IHD, PVD and all-cause mortality (but not HF or ischaemic stroke) increased significantly with worsening self-rated health of teeth and gums (ptrend<0.05). In those reporting poor versus very good health of teeth and gums, risks were increased for IHD (1.19, 1.03 to 1.38), PVD (1.66, 1.13 to 2.43) and all-cause mortality (1.76, 1.50 to 2.08). Conclusions Tooth loss and, to a lesser extent, self

  14. Label-free visualization of collagen in submucosa as a potential diagnostic marker for early detection of colorectal cancer

    NASA Astrophysics Data System (ADS)

    Qiu, Jingting; Yang, Yinghong; Jiang, Weizhong; Feng, Changyin; Chen, Zhifen; Guan, Guoxian; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

    2014-09-01

    The collagen signature in colorectal submucosa is changed due to remodeling of the extracellular matrix during the malignant process and plays an important role in noninvasive early detection of human colorectal cancer. In this work, multiphoton microscopy (MPM) was used to monitor the changes of collagen in normal colorectal submucosa (NCS) and cancerous colorectal submucosa (CCS). What's more, the collagen content was quantitatively measured. It was found that in CCS the morphology of collagen becomes much looser and the collagen content is significantly reduced compared to NCS. These results suggest that MPM has the ability to provide collagen signature as a potential diagnostic marker for early detection of colorectal cancer.

  15. MTHFR Gene Mutations: A Potential Marker of Late-Onset Alzheimer's Disease?

    PubMed

    Román, Gustavo C

    2015-01-01

    Recent epigenome-wide association studies have confirmed the importance of epigenetic effects mediated by DNA methylation in late-onset Alzheimer's disease (LOAD). Metabolic folate pathways and methyl donor reactions facilitated by B-group vitamins may be critical in the pathogenesis of LOAD. Methylenetetrahydrofolate reductase (MTHFR) gene mutations were studied in consecutive Alzheimer's Disease & Memory Clinic patients up to December 2014. DNA analyses of MTHFR-C667T and - A1298C homozygous and heterozygous polymorphisms in 93 consecutive elderly patients revealed high prevalence of MTHFR mutations (92.5%). Findings require confirmation in a larger series, but MTHFR mutations may become a LOAD marker, opening novel possibilities for prevention and treatment. PMID:26401555

  16. Proteomics-based identification of α-enolase as a potential prognostic marker in cholangiocarcinoma

    PubMed Central

    Yonglitthipagon, Ponlapat; Pairojkul, Chawalit; Bhudhisawasdi, Vajarabhongsa; Mulvenna, Jason; Loukas, Alex; Sripa, Banchob

    2012-01-01

    Objectives To investigate the association of expression status of α-enolase (ENO1) and clinicopathological outcomes of CCA patients. Design and methods Two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) were used to compare differential expressed protein profiles of four human CCA cell lines and H69, a non-malignant biliary cell line, as a control. Immunohistochemical analysis was carried out in tissue-microarray of human CCA tissues (n = 301). Results We identified ENO1 in all CCA cell lines but not H69 by proteomics based. About 75% of patients with CCA showed over-expression of ENO1 in hyperplastic bile duct and the tumors compared with that in tumor-adjacent normal tissue counterparts. Moreover, over-expression of ENO1 is significantly associated with poor prognosis and tumor invasion of CCA patients. Conclusions ENO1 may serve as a prognostic marker to monitor the disease progression of these patients. PMID:22552009

  17. Corrosion in the oral cavity--potential local and systemic effects.

    PubMed

    Bergman, M

    1986-03-01

    The main current-generating corrosion cells in the oral cavity are the bimetallic cell and the concentration cell, the latter mainly occurring due to differences in access to oxygen in the various parts of the metallic material. Corrosion resistance is not an intrinsic property of a metal or an alloy for it depends on an interaction with the environment. Thus, the contents of the oral cavity, have a decisive influence. This implies that corrosion tests in vitro are of limited value in predicting the clinical corrosion behaviour of a metallic material. Results from a series of clinical studies concerning a possible relationship between galvanic currents and certain oral and other symptoms in a group of patients who had been referred to the Faculty of Odontology, University of Umeå, are briefly presented. The possibility of local and systemic effects of intra-oral galvanic cells is discussed. PMID:3457767

  18. Kinesin family member 14: an independent prognostic marker and potential therapeutic target for ovarian cancer.

    PubMed

    Thériault, Brigitte L; Pajovic, Sanja; Bernardini, Marcus Q; Shaw, Patricia A; Gallie, Brenda L

    2012-04-15

    The novel oncogene KIF14 (kinesin family member 14) shows genomic gain and overexpression in many cancers including OvCa (ovarian cancer). We discovered that expression of the mitotic kinesin KIF14 is predictive of poor outcome in breast and lung cancers. We now determine the prognostic significance of KIF14 expression in primary OvCa tumors, and evaluate KIF14 action on OvCa cell tumorigenicity in vitro. Gene-specific multiplex PCR and real-time QPCR were used to measure KIF14 genomic (109 samples) and mRNA levels (122 samples) in OvCa tumors. Association of KIF14 with clinical variables was studied using Kaplan-Meier survival and Cox regression analyses. Cellular effects of KIF14 overexpression (stable transfection) and inhibition (stable shRNA knockdown) were studied by proliferation (cell counts), survival (Annexin V immunocytochemistry) and colony formation (soft-agar growth). KIF14 genomic gain (>2.6 copies) was present in 30% of serous OvCas, and KIF14 mRNA was elevated in 91% of tumors versus normal epithelium. High KIF14 in tumors independently predicted for worse outcome (p = 0.03) with loss of correlation with proliferation marker expression and increased rates of recurrence. Overexpression of KIF14 in OvCa cell lines increased proliferation and colony formation (p < 0.01), whereas KIF14 knockdown induced apoptosis and dramatically reduced colony formation (p < 0.05). Our findings indicate that KIF14 mRNA is an independent prognostic marker in serous OvCa. Dependence of OvCa cells on KIF14 for maintenance of in vitro colony formation suggests a role of KIF14 in promoting a tumorigenic phenotype, beyond its known role in proliferation. PMID:21618518

  19. Cavin-2 in oral cancer: A potential predictor for tumor progression.

    PubMed

    Unozawa, Motoharu; Kasamatsu, Atsushi; Higo, Morihiro; Fukumoto, Chonji; Koyama, Tomoyoshi; Sakazume, Tomomi; Nakashima, Dai; Ogawara, Katsunori; Yokoe, Hidetaka; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

    2016-06-01

    Cavin-2 (CVN2) affects formation of large caveolae, which are membrane-rich cholesterol domains associated with several functions in signal transduction. Accumulating evidence suggests that CVN2 is present in many cellular types; however, the molecular mechanisms of CVN2 in cancers and its clinical relevance are unknown. We proposed a mechanism by which CVN2 regulates caveolin-1 expression leading to slow cellular proliferation by inactivation of the extracellular regulated kinase (ERK) pathway. Quantitative reverse transcriptase-polymerase chain reaction and immunoblot analyses were used to assess the CVN2 regulation mechanism in oral squamous cell carcinoma (OSCC). Immunohistochemistry (IHC) was performed to analyze the correlation between CVN2 expression and clinical behavior in 115 patients with OSCC. A CVN2 overexpressed model of OSCC cells (oeCVN2 cells) was used for functional experiments. CVN2 expression was down-regulated significantly (P < 0.05) in OSCCs compared with normal counterparts in vitro and in vivo. In addition to the findings that a serum deprivation culture induced up-regulation of CVN2 and slowed cellular proliferation, oeCVN2 cell growth decreased because of cell-cycle arrest at the G1 phase resulting from up-regulated cyclin-dependent kinase inhibitors (p21(Cip1) and p27(Kip1) ) and down-regulated cyclins (cyclin D1, cyclin E) and cyclin-dependent kinases (CDK2, CDK4, and CDK6). Interestingly, CVN2 overexpression facilitated caveolin-1 recruitment and colocalization with each other. We also found decreased ERK phosphorylation levels, an upstream event in cell-cycle arrest. Clinically, IHC data from primary OSCCs showed high tumoral progression in CVN2-negative patients with OSCC. CVN2 may be a possible key regulator of OSCC progression via the CVN2/caveolin-1/ERK pathway and a potential therapeutic target for developing new treatments for OSCCs. © 2015 Wiley Periodicals, Inc. PMID:26086332

  20. 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

  1. 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

  2. The chloroplast DNA locus psbZ-trnfM as a potential barcode marker in Phoenix L. (Arecaceae)

    PubMed Central

    Ballardini, Marco; Mercuri, Antonio; Littardi, Claudio; Abbas, Summar; Couderc, Marie; Ludeña, Bertha; Pintaud, Jean-Christophe

    2013-01-01

    Abstract The genus Phoenix (Arecaceae) comprises 14 species distributed from Cape Verde Islands to SE Asia. It includes the economically important species Phoenix dactylifera. The paucity of differential morphological and anatomical useful characters, and interspecific hybridization, make identification of Phoenix species difficult. In this context, the development of reliable DNA markers for species and hybrid identification would be of great utility. Previous studies identified a 12 bp polymorphic chloroplast minisatellite in the trnG (GCC)-trnfM (CAU) spacer, and showed its potential for species identification in Phoenix. In this work, in order to develop an efficient DNA barcode marker for Phoenix, a longer cpDNA region (700 bp) comprising the mentioned minisatellite, and located between the psbZ and trnfM (CAU) genes, was sequenced. One hundred and thirty-six individuals, representing all Phoenix species except P. andamanensis,were analysed. The minisatellite showed 2-7 repetitions of the 12 bp motif, with 1-3 out of seven haplotypes per species. Phoenix reclinata and P. canariensis had species-specific haplotypes. Additional polymorphisms were found in the flanking regions of the minisatellite, including substitutions, indels and homopolymers. All this information allowed us to identify unambiguously eight out of the 13 species, and overall 80% of the individuals sampled. Phoenix rupicola and P. theophrasti had the same haplotype, and so had P. atlantica, P. dactylifera, and P. sylvestris (the “date palm complex” sensu Pintaud et al. 2013). For these species, additional molecular markers will be required for their unambiguous identification. The psbZ-trnfM (CAU) region therefore could be considered as a good basis for the establishment of a DNA barcoding system in Phoenix, and is potentially useful for the identification of the female parent in Phoenix hybrids. PMID:24453552

  3. In situ marker-based assessment of leaf trait evolutionary potential in a marginal European beech population.

    PubMed

    Bontemps, A; Lefèvre, F; Davi, H; Oddou-Muratorio, S

    2016-03-01

    Evolutionary processes are expected to be crucial for the adaptation of natural populations to environmental changes. In particular, the capacity of rear edge populations to evolve in response to the species limiting conditions remains a major issue that requires to address their evolutionary potential. In situ quantitative genetic studies based on molecular markers offer the possibility to estimate evolutionary potentials manipulating neither the environment nor the individuals on which phenotypes are measured. The goal of this study was to estimate heritability and genetic correlations of a suite of leaf functional traits involved in climate adaptation for a natural population of the tree Fagus sylvatica, growing at the rear edge of the species range. Using two marker-based quantitative genetics approaches, we obtained consistent and significant estimates of heritability for leaf phenological (phenology of leaf flush), morphological (mass, area, ratio mass/area) and physiological (δ(13)C, nitrogen content) traits. Moreover, we found only one significant positive genetic correlation between leaf area and leaf mass, which likely reflected mechanical constraints. We conclude first that the studied population has considerable genetic diversity for important ecophysiological traits regarding drought adaptation and, second, that genetic correlations are not likely to impose strong genetic constraints to future population evolution. Our results bring important insights into the question of the capacity of rear edge populations to evolve. PMID:26679342

  4. Volatile fingerprint of Brazilian defective coffee seeds: corroboration of potential marker compounds and identification of new low quality indicators.

    PubMed

    Toci, Aline T; Farah, Adriana

    2014-06-15

    In the present work, the volatile profiles of green and roasted Brazilian defective coffee seeds and their controls were characterised, totalling 159 compounds. Overall, defective seeds showed higher number and concentration of volatile compounds compared to those of control seeds, especially pyrazines, pyrroles and phenols. Corroborating our previous results, butyrolactone and hexanoic acid, previously considered as potential defective seeds' markers, were observed only in raw and roasted defective seeds, respectively, and not in control seeds. New compounds were suggested as potential defective seeds' markers: hexanoic acid (for raw and roasted defective seeds in general), butyrolactone (for raw defective seeds in general), and 3-ethyl-2-methyl-1,3-hexadiene (for raw black seeds); β-linalool and 2-butyl-3,5-dimethylpyrazine (for roasted defective seeds in general), and 2-pentylfuran (for roasted black seeds). Additional compounds suggested as low quality indicators were 2,3,5,6-tetramethylpyrazine,2,3-butanediol and 4-ethylguaiacol, β-linalool, 2-,3-dimethylbutyl butanoate, 2-phenylethyl acetate, 2,3-butanedione, hexanedioic acid, guaiacol, 2,3-dihydro-2-methyl-1H-benzopyrrol, 3-methylpiperidine, 2-pentylpiperidine, 3-octen-2-one, 2-octenal, 2-pentylfuran and 2-butyl-3-methylpyrazine. PMID:24491734

  5. Resistin as a potential marker of renal disease in lupus nephritis.

    PubMed

    Hutcheson, J; Ye, Y; Han, J; Arriens, C; Saxena, R; Li, Q-Z; Mohan, C; Wu, T

    2015-03-01

    Systemic lupus erythematosus (SLE) and lupus nephritis (LN) have strong concomitance with cardiovascular disease that cannot be explained fully by typical risk factors. We examined the possibility that serum or urine expression of adipokines may act as biomarkers for LN, as these proteins have been associated previously with cardiovascular disease as well as SLE. Antibody arrays were performed on serum and urine from lupus patients and matched controls using a cross-sectional study design. From the initial array-based screening data of 15 adipokines, adiponectin, leptin and resistin were selected for validation by enzyme-linked immunosorbent assay (ELISA). Correlations were determined between adipokine expression levels and measures of disease activity or lupus nephritis. The expression of adiponectin and resistin was increased in both sera and urine from LN patients, while leptin was increased in LN patient sera, compared to matched controls. Serum resistin, but not urine resistin, was correlated with measures of renal dysfunction in LN. Serum resistin expression may be useful as a marker of renal dysfunction in patients with LN, although longitudinal studies are warranted. Further studies are necessary to determine if resistin has functional consequences in LN. PMID:25345756

  6. Human AP Endonuclease 1: A Potential Marker for the Prediction of Environmental Carcinogenesis Risk

    PubMed Central

    Park, Jae Sung; Kim, Hye Lim; Kim, Yeo Jin; Weon, Jong-Il; Sung, Mi-Kyung; Chung, Hai Won; Seo, Young Rok

    2014-01-01

    Human apurinic/apyrimidinic endonuclease 1 (APE1) functions mainly in DNA repair as an enzyme removing AP sites and in redox signaling as a coactivator of various transcription factors. Based on these multifunctions of APE1 within cells, numerous studies have reported that the alteration of APE1 could be a crucial factor in development of human diseases such as cancer and neurodegeneration. In fact, the study on the combination of an individual's genetic make-up with environmental factors (gene-environment interaction) is of great importance to understand the development of diseases, especially lethal diseases including cancer. Recent reports have suggested that the human carcinogenic risk following exposure to environmental toxicants is affected by APE1 alterations in terms of gene-environment interactions. In this review, we initially outline the critical APE1 functions in the various intracellular mechanisms including DNA repair and redox regulation and its roles in human diseases. Several findings demonstrate that the change in expression and activity as well as genetic variability of APE1 caused by environmental chemical (e.g., heavy metals and cigarette smoke) and physical carcinogens (ultraviolet and ionizing radiation) is likely associated with various cancers. These enable us to ultimately suggest APE1 as a vital marker for the prediction of environmental carcinogenesis risk. PMID:25243052

  7. Cytochrome c as a Potentially Clinical Useful Marker of Mitochondrial and Cellular Damage

    PubMed Central

    Eleftheriadis, Theodoros; Pissas, Georgios; Liakopoulos, Vassilios; Stefanidis, Ioannis

    2016-01-01

    Mitochondria are evolutionary endosymbionts derived from bacteria. Thus, they bear molecules, such as mitochondrial DNA (mtDNA) that contains CpG DNA repeats and N-formyl peptides (FPs), found in bacteria. Upon cell necrosis or apoptosis, these molecules are released into the interstitial space and the circulation and recognized by the immune cells through the same receptors that recognize pathogen-associated molecular patterns, leading to inflammation. Other mitochondrial molecules are not of bacterial origin, but they may serve as danger-associated molecular patterns (DAMPs) when due to cell injury are translocated into inappropriate compartments. There they are recognized by pattern recognition receptors of the immune cells. Cytochrome c is such a molecule. In this review, experimental and clinical data are presented that confirms cytochrome c release into the extracellular space in pathological conditions characterized by cell death. This indicates that serum cytochrome c, which can be easily measured, may be a clinically useful marker for diagnosing and assessing the severity of such pathological entities. Reasonably, detection of high cytochrome c level into the circulation means release of various other molecules that serves as DAMPs when found extracellularly, the mtDNA and FPs included. Finally, because the release of this universally found compound into the extracellular space makes cytochrome c an ideal molecule to play the role of a DAMP per se, the available experimental and clinical data that support such a role are provided. PMID:27489552

  8. Basal cytokeratin as a potential marker of low risk of invasion in ductal carcinoma in situ

    PubMed Central

    Aguiar, Fernando N.; Mendes, Henrique N.; Cirqueira, Cinthya S.; Bacchi, Carlos E.; Carvalho, Filomena M.

    2013-01-01

    OBJECTIVES: Biological markers that predict the development of invasive breast cancer are needed to improve personalized therapy for patients diagnosed with ductal carcinoma in situ. We investigated the role of basal cytokeratin 5/6 in the risk of invasion in breast ductal carcinoma in situ. METHODS: We constructed tissue microarrays using 236 ductal carcinoma in situ samples: 90 pure samples (group 1) and 146 samples associated with invasive carcinoma (group 2). Both groups had similar nuclear grades and were obtained from patients of similar ages. The groups were compared in terms of estrogen (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) expression, cytokeratin 5/6 immunostaining, human epidermal growth factor receptor 1 (EGFR) membrane staining and molecular subtype, as indicated by their immunohistochemistry profiles. RESULTS: ER/PR-negative status was predictive of invasion, whereas HER2 superexpression and cytokeratin 5/6-positive status were negatively associated with invasion. Among the high-grade ductal carcinoma in situ cases, a triple-positive profile (positive for estrogen receptor, progesterone receptor, and HER2) and cytokeratin 5/6 expression by neoplastic cells were negatively associated with invasion. In the low-grade ductal carcinoma in situ subgroup, only cytokeratin 5/6 expression exhibited a negative association with the probability of invasion. CONCLUSION: The immunohistochemical expression of cytokeratin 5/6 by ductal carcinoma in situ epithelial cells may provide clinically useful information regarding the risk of progression to invasive disease. PMID:23778411

  9. Resistin as a potential marker of renal disease in lupus nephritis

    PubMed Central

    Hutcheson, J; Ye, Y; Han, J; Arriens, C; Saxena, R; Li, Q-Z; Mohan, C; Wu, T

    2015-01-01

    Systemic lupus erythematosus (SLE) and lupus nephritis (LN) have strong concomitance with cardiovascular disease that cannot be explained fully by typical risk factors. We examined the possibility that serum or urine expression of adipokines may act as biomarkers for LN, as these proteins have been associated previously with cardiovascular disease as well as SLE. Antibody arrays were performed on serum and urine from lupus patients and matched controls using a cross-sectional study design. From the initial array-based screening data of 15 adipokines, adiponectin, leptin and resistin were selected for validation by enzyme-linked immunosorbent assay (ELISA). Correlations were determined between adipokine expression levels and measures of disease activity or lupus nephritis. The expression of adiponectin and resistin was increased in both sera and urine from LN patients, while leptin was increased in LN patient sera, compared to matched controls. Serum resistin, but not urine resistin, was correlated with measures of renal dysfunction in LN. Serum resistin expression may be useful as a marker of renal dysfunction in patients with LN, although longitudinal studies are warranted. Further studies are necessary to determine if resistin has functional consequences in LN. PMID:25345756

  10. Structural chromosomal aberrations as potential risk markers in incident cancer patients.

    PubMed

    Vodenkova, Sona; Polivkova, Zdenka; Musak, Ludovit; Smerhovsky, Zdenek; Zoubkova, Hana; Sytarova, Sylvie; Kavcova, Elena; Halasova, Erika; Vodickova, Ludmila; Jiraskova, Katerina; Svoboda, Miroslav; Ambrus, Miloslav; Hemminki, Kari; Vodicka, Pavel

    2015-07-01

    Epidemiological prospective studies have shown that increased chromosomal aberrations (CAs) in peripheral blood lymphocytes may predict cancer risk. Here, we report CAs in newly diagnosed 101 colorectal, 87 lung and 158 breast cancer patients and corresponding healthy controls. Strong differences in distributions of aberrant cells (ACs), CAs, chromatid-type aberrations (CTAs) and chromosome-type aberrations (CSAs) were observed in lung and breast cancer patients as compared to healthy controls. In colorectal cancer (CRC) patients, only CTAs were significantly elevated. Binary logistic regression, adjusted for main confounders, indicates that all the analysed cytogenetic parameters along with smoking were significantly associated with breast and lung cancer risks. Significant differences in terminal deletions between breast cancer patients and corresponding female controls were recorded (0.39 vs. 0.18; P ≤ 0.05). We did not find any association of CAs with TNM (tumor nodus metastasis) stages or histopathological grade in either cancer type. CAs were neither associated with additional tumor characteristics-invasivity, ductal and lobular character, estrogene/progesterone receptors in breast tumors nor with non-small/small cell and bronchogenic/pulmonary types of lung tumors. Our study demonstrates that CAs serve as a predictive marker for breast and lung cancer, whereas only CTAs were elevated in incident CRC patients. PMID:25800034

  11. Intraindividual variability across cognitive tasks as a potential marker for prodromal Alzheimer's disease.

    PubMed

    Kälin, Andrea M; Pflüger, Marlon; Gietl, Anton F; Riese, Florian; Jäncke, Lutz; Nitsch, Roger M; Hock, Christoph

    2014-01-01

    Recent studies have shown that increased cognitive intraindividual variability (IIV) across accuracy scores from tests representing different cognitive domains (across-domain IIV) might indicate prodromal Alzheimer's disease (AD). Although IIV has been proposed to index cognitive control processes, IIV across accuracy scores from cognitive control tasks (within-domain IIV) has not been examined in healthy controls subjects (HCS), mild cognitive impairment (MCI), and AD patients in a single comparative study. This study examines the discriminative properties of within-domain IIV, and across-domain IIV in 149 HCS, 31 MCI, and 26 AD. Three tasks representing different cognitive domains were identified to calculate across-domain IIV. Three other tasks representing cognitive control were identified to calculate within-domain IIV. The intraindividual standard deviation was calculated across accuracy scores. To compare IIV between groups, ANCOVAs with the covariates age, gender, education, and mean performance were computed. IIV scores in general were higher in AD vs. HCS (p < 0.01). Only across-domain IIV was higher in AD vs. MCI (p = 0.001), and only within-domain IIV was higher in MCI vs. HCS (p = 0.05). Within-domain IIV may constitute a cognitive marker for the detection of prodromal AD at the MCI stage, whereas across-domain IIV may detect beginning AD at the MCI stage. PMID:25071556

  12. Intraindividual variability across cognitive tasks as a potential marker for prodromal Alzheimer’s disease

    PubMed Central

    Kälin, Andrea M.; Pflüger, Marlon; Gietl, Anton F.; Riese, Florian; Jäncke, Lutz; Nitsch, Roger M.; Hock, Christoph

    2014-01-01

    Recent studies have shown that increased cognitive intraindividual variability (IIV) across accuracy scores from tests representing different cognitive domains (across-domain IIV) might indicate prodromal Alzheimer’s disease (AD). Although IIV has been proposed to index cognitive control processes, IIV across accuracy scores from cognitive control tasks (within-domain IIV) has not been examined in healthy controls subjects (HCS), mild cognitive impairment (MCI), and AD patients in a single comparative study. This study examines the discriminative properties of within-domain IIV, and across-domain IIV in 149 HCS, 31 MCI, and 26 AD. Three tasks representing different cognitive domains were identified to calculate across-domain IIV. Three other tasks representing cognitive control were identified to calculate within-domain IIV. The intraindividual standard deviation was calculated across accuracy scores. To compare IIV between groups, ANCOVAs with the covariates age, gender, education, and mean performance were computed. IIV scores in general were higher in AD vs. HCS (p < 0.01). Only across-domain IIV was higher in AD vs. MCI (p = 0.001), and only within-domain IIV was higher in MCI vs. HCS (p = 0.05). Within-domain IIV may constitute a cognitive marker for the detection of prodromal AD at the MCI stage, whereas across-domain IIV may detect beginning AD at the MCI stage. PMID:25071556

  13. Gene Expression Changes in Developing Zebrafish as Potential Markers for Rapid Developmental Neurotoxicity Screening

    EPA Science Inventory

    Sparse information exists on many chemicals to guide developmental neurotoxicity (DNT) risk assessments. As DNT testing using rodents is laborious and expensive, alternative species such as zebrafish are being adapted for toxicity screening. Assessing the DNT potential of chem...

  14. Marker-Trait Association for Biomass Yield of Potential Bio-fuel Feedstock Miscanthus sinensis from Southwest China

    PubMed Central

    Nie, Gang; Huang, Linkai; Zhang, Xinquan; Taylor, Megan; Jiang, Yiwei; Yu, Xiaoqing; Liu, Xinchun; Wang, Xinyu; Zhang, Yajie

    2016-01-01

    As a great potential bio-fuel feedstock, the genus Miscanthus has been widely studied around the world, especially Miscanthus × giganteus owing to its high biomass yield in Europe and North America. However, the narrow genetic basis and sterile characteristics of M. × giganteus have become a limitation for utilization and adaptation to extreme climate conditions. In this study, we focused on one of the progenitors of M. × giganteus, Miscanthus sinensis, which was originally distributed in East Asia with abundant genetic resources and comparable biomass yield potential to M. × giganteus in some areas. A collection of 138 individuals was selected for conducting a 3-year trial of biomass production and analyzed by using 104 pairs of SRAP, ISAP, and SSR primers for genetic diversity as well as marker-trait association. Significant differences in biomass yield and related traits were observed among individuals. Tiller number, fresh biomass yield per plant and dry biomass yield per plant had a high level of phenotypic variation among individuals and the coefficient of variation were all above 40% in 2011, 2012, and 2013. The majority of the traits had a significant correlation with the biomass yield except for the length and width of flag leaves. Plant height was a highly stable trait correlated with biomass yield. A total of 1059 discernible loci were detected by markers across individuals. The population structure (Q) and cluster analyses identified three subpopulations in the collection and family relative kinship (K) represented high gene flow among M. sinensis populations from Southwest China. Model testing identified that Q+K was the best model for describing the associations between the markers and traits, compared to the simple linear, Q or K model. Using the Q+K model, 12 significant associations (P < 0.001) were identified including four markers with plant height and one with biomass yield. Such associations would serve an efficient tool for an early

  15. Marker-Trait Association for Biomass Yield of Potential Bio-fuel Feedstock Miscanthus sinensis from Southwest China.

    PubMed

    Nie, Gang; Huang, Linkai; Zhang, Xinquan; Taylor, Megan; Jiang, Yiwei; Yu, Xiaoqing; Liu, Xinchun; Wang, Xinyu; Zhang, Yajie

    2016-01-01

    As a great potential bio-fuel feedstock, the genus Miscanthus has been widely studied around the world, especially Miscanthus × giganteus owing to its high biomass yield in Europe and North America. However, the narrow genetic basis and sterile characteristics of M. × giganteus have become a limitation for utilization and adaptation to extreme climate conditions. In this study, we focused on one of the progenitors of M. × giganteus, Miscanthus sinensis, which was originally distributed in East Asia with abundant genetic resources and comparable biomass yield potential to M. × giganteus in some areas. A collection of 138 individuals was selected for conducting a 3-year trial of biomass production and analyzed by using 104 pairs of SRAP, ISAP, and SSR primers for genetic diversity as well as marker-trait association. Significant differences in biomass yield and related traits were observed among individuals. Tiller number, fresh biomass yield per plant and dry biomass yield per plant had a high level of phenotypic variation among individuals and the coefficient of variation were all above 40% in 2011, 2012, and 2013. The majority of the traits had a significant correlation with the biomass yield except for the length and width of flag leaves. Plant height was a highly stable trait correlated with biomass yield. A total of 1059 discernible loci were detected by markers across individuals. The population structure (Q) and cluster analyses identified three subpopulations in the collection and family relative kinship (K) represented high gene flow among M. sinensis populations from Southwest China. Model testing identified that Q+K was the best model for describing the associations between the markers and traits, compared to the simple linear, Q or K model. Using the Q+K model, 12 significant associations (P < 0.001) were identified including four markers with plant height and one with biomass yield. Such associations would serve an efficient tool for an early

  16. DNA microarray analysis identifies CKS2 and LEPR as potential markers of meningioma recurrence.

    PubMed

    Menghi, Francesca; Orzan, Francesca N; Eoli, Marica; Farinotti, Mariangela; Maderna, Emanuela; Pisati, Federica; Bianchessi, Donatella; Valletta, Lorella; Lodrini, Sandro; Galli, Giuseppe; Anghileri, Elena; Pellegatta, Serena; Pollo, Bianca; Finocchiaro, Gaetano

    2011-01-01

    Meningiomas are the most frequent intracranial tumors. Surgery can be curative, but recurrences are possible. We performed gene expression analyses and loss of heterozygosity (LOH) studies looking for new markers predicting the recurrence risk. We analyzed expression profiles of 23 meningiomas (10 grade I, 10 grade II, and 3 grade III) and validated the data using quantitative polymerase chain reaction (qPCR). We performed LOH analysis on 40 meningiomas, investigating chromosomal regions on 1p, 9p, 10q, 14q, and 22q. We found 233 and 268 probe sets to be significantly down- and upregulated, respectively, in grade II or III meningiomas. Genes downregulated in high-grade meningiomas were overrepresented on chromosomes 1, 6, 9, 10, and 14. Based on functional enrichment analysis, we selected LIM domain and actin binding 1 (LIMA1), tissue inhibitor of metalloproteinases 3 (TIMP3), cyclin-dependent kinases regulatory subunit 2 (CKS2), leptin receptor (LEPR), and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) for validation using qPCR and confirmed their differential expression in the two groups of tumors. We calculated ΔCt values of CKS2 and LEPR and found that their differential expression (C-L index) was significantly higher in grade I than in grade II or III meningiomas (p < .0001). Interestingly, the C-L index of nine grade I meningiomas from patients who relapsed in <5 years was significantly lower than in grade I meningiomas from patients who did not relapse. These findings indicate that the C-L index may be relevant to define the progression risk in meningioma patients, helping guide their clinical management. A prospective analysis on a larger number of cases is warranted. PMID:21948653

  17. Assessment of Environmental and Hereditary Influence on Development of Pituitary Tumors Using Dermatoglyphic Traits and Their Potential as Screening Markers

    PubMed Central

    Gradiser, Marina; Matovinovic Osvatic, Martina; Dilber, Dario; Bilic-Curcic, Ines

    2016-01-01

    The aim of this study was to assess environmental and hereditary influence on development of pituitary tumors using dermatoglyphic traits. The study was performed on 126 patients of both genders with pituitary tumors (60 non-functional and 66 functional pituitary tumor patients) in comparison to the control group of 400 phenotypically healthy individuals. Statistical analysis of quantitative and qualitative traits of digito-palmar dermatoglyphics was performed, and hormonal status was determined according to the standard protocols. Although we did not find markers that could specifically distinguish functional from non-functional tumors, we have found markers predisposing to the development of tumors in general (a small number of ridges between triradius of both hands, a smaller number of ridges between the triradius of c–d rc R), those for endocrine dysfunction (increased number of arches and reduced number of whorls, difference of pattern distribution in the I3 and I4 interdigital space), and some that could potentially be attributed to patients suffering from pituitary tumors (small number of ridges for variables FRR 5, smaller number of ridges in the FRL 4 of both hands and difference of pattern distribution at thenar of I1 and I2 interdigital space). The usage of dermatoglyphic traits as markers of predisposition of pituitary tumor development could facilitate the earlier detection of patients in addition to standard methods, and possibly earlier treatment and higher survival rate. Finally, our results are consistent with the hypothesis about multifactorial nature of pituitary tumor etiology comprised of both gene instability and environmental factors. PMID:26999178

  18. TRANSGELIN: A POTENTIALLY USEFUL DIAGNOSTIC MARKER DIFFERENTIALLY EXPRESSED IN TRIPLE-NEGATIVE AND NON-TRIPLE NEGATIVE BREAST CANCERS

    PubMed Central

    Rao, Deepthi; Kimler, Bruce F; Nothnick, Warren B; Davis, Marilyn K; Fan, Fang; Tawfik, Ossama

    2015-01-01

    Triple negative (TN) (estrogen receptor [ER], progesterone receptor [PR] and Her2 negative) are highly aggressive, rapidly growing, hormone unresponsive tumors diagnosed at later stage that affect younger women with shorter overall survival. The majority of TN tumors are of the basal type. For the remainder identification of target markers for effective treatment strategies remains a challenge. Transgelin (TGLN) is a 22 kDa actin-binding protein of the calponin family. It is one of the earliest markers of smooth muscle differentiation. TGLN has been shown to have important biologic activities including regulating muscle fiber contractility, cell migration and tumor suppression. We examined TGLN expression in the different molecular subtypes of breast cancer. TGLN expression was examined as a function of tumor size, grade, histologic type, lymph node (LN) status, patients’ age and overall survival, ER, PR, Her-2, Ki-67 in 101 tumors that included 35 luminal A, 28 luminal B, 4 Her2, and 34 TN types. TGLN positivity (defined as 2+ or 3+) was associated with more aggressive tumors (10% of grade I/II tumors were TGLN+ vs. 53% of grade III tumors, P<0.001), high Ki-67 count and low ER and PR expression (p<0.001), but not with tumor size, age or LN metastasis. TN (n=34) tumors were 7.7 times more likely to be TGLN-positive than non-TN (n=67) tumors (77% vs. 10%, respectively, P<0.001). TGLN may be an excellent diagnostic marker of TN tumors and could be useful in stratification of patients. TGLN may also prove a potential target for future treatment strategies. PMID:25841305

  19. Assessment of Environmental and Hereditary Influence on Development of Pituitary Tumors Using Dermatoglyphic Traits and Their Potential as Screening Markers.

    PubMed

    Gradiser, Marina; Matovinovic Osvatic, Martina; Dilber, Dario; Bilic-Curcic, Ines

    2016-01-01

    The aim of this study was to assess environmental and hereditary influence on development of pituitary tumors using dermatoglyphic traits. The study was performed on 126 patients of both genders with pituitary tumors (60 non-functional and 66 functional pituitary tumor patients) in comparison to the control group of 400 phenotypically healthy individuals. Statistical analysis of quantitative and qualitative traits of digito-palmar dermatoglyphics was performed, and hormonal status was determined according to the standard protocols. Although we did not find markers that could specifically distinguish functional from non-functional tumors, we have found markers predisposing to the development of tumors in general (a small number of ridges between triradius of both hands, a smaller number of ridges between the triradius of c-d rc R), those for endocrine dysfunction (increased number of arches and reduced number of whorls, difference of pattern distribution in the I3 and I4 interdigital space), and some that could potentially be attributed to patients suffering from pituitary tumors (small number of ridges for variables FRR 5, smaller number of ridges in the FRL 4 of both hands and difference of pattern distribution at thenar of I1 and I2 interdigital space). The usage of dermatoglyphic traits as markers of predisposition of pituitary tumor development could facilitate the earlier detection of patients in addition to standard methods, and possibly earlier treatment and higher survival rate. Finally, our results are consistent with the hypothesis about multifactorial nature of pituitary tumor etiology comprised of both gene instability and environmental factors. PMID:26999178

  20. Genome-wide survey and analysis of microsatellites in the Pacific oyster genome: abundance, distribution, and potential for marker development

    NASA Astrophysics Data System (ADS)

    Wang, Jiafeng; Qi, Haigang; Li, Li; Zhang, Guofan

    2014-01-01

    Microsatellites are a ubiquitous component of the eukaryote genome and constitute one of the most popular sources of molecular markers for genetic studies. However, no data are currently available regarding microsatellites across the entire genome in oysters, despite their importance to the aquaculture industry. We present the first genome-wide investigation of microsatellites in the Pacific oyster Crassostrea gigas by analysis of the complete genome, resequencing, and expression data. The Pacific oyster genome is rich in microsatellites. A total of 604 653 repeats were identified, in average of one locus per 815 base pairs (bp). A total of 12 836 genes had coding repeats, and 7 332 were expressed normally, including genes with a wide range of molecular functions. Compared with 20 different species of animals, microsatellites in the oyster genome typically exhibited 1) an intermediate overall frequency; 2) relatively uniform contents of (A)n and (C)n repeats and abundant long (C)n repeats (≥24 bp); 3) large average length of (AG)n repeats; and 4) scarcity of trinucleotide repeats. The microsatellite-flanking regions exhibited a high degree of polymorphism with a heterozygosity rate of around 2.0%, but there was no correlation between heterozygosity and microsatellite abundance. A total of 19 462 polymorphic microsatellites were discovered, and dinucleotide repeats were the most active, with over 26% of loci found to harbor allelic variations. In all, 7 451 loci with high potential for marker development were identified. Better knowledge of the microsatellites in the oyster genome will provide information for the future design of a wide range of molecular markers and contribute to further advancements in the field of oyster genetics, particularly for molecular-based selection and breeding.

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

    PubMed

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

    2012-12-01

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

  2. Neospora caninum surface antigen (p40) is a potential diagnostic marker for cattle neosporosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neospora caninum is an intracellular protozoan that infects domestic and wild canids as well as many warm-blooded animals as shown by the isolation of viable parasites. The effectiveness of diagnostic tests for detecting specific antibodies against N. caninum is hampered by potential cross-reaction ...

  3. Potential for Metabolomics-Based Markers of Exposure:Encouraging Evidence from Studies using Model Organisms

    EPA Science Inventory

    Genomic techniques (transcriptomics, proteomics, and metabolomics) have the potential to significantly improve the way chemical risk is managed in the 21st century. Indeed, a significant amount of research has been devoted to the use of these techniques to screen chemicals for h...

  4. In vitro cell motility as a potential mesenchymal stem cell marker for multipotency.

    PubMed

    Bertolo, Alessandro; Gemperli, Armin; Gruber, Marco; Gantenbein, Benjamin; Baur, Martin; Pötzel, Tobias; Stoyanov, Jivko

    2015-01-01

    Mesenchymal stem cells (MSCs) are expected to have a fundamental role in future cell-based therapies because of their high proliferative ability, multilineage potential, and immunomodulatory properties. Autologous transplantations have the "elephant in the room" problem of wide donor variability, reflected by variability in MSC quality and characteristics, leading to uncertain outcomes in the use of these cells. We propose life imaging as a tool to characterize populations of human MSCs. Bone marrow MSCs from various donors and in vitro passages were evaluated for their in vitro motility, and the distances were correlated to the adipogenic, chondrogenic, and osteogenic differentiation potentials and the levels of senescence and cell size. Using life-image measuring of track lengths of 70 cells per population for a period of 24 hours, we observed that slow-moving cells had the higher proportion of senescent cells compared with fast ones. Larger cells moved less than smaller ones, and spindle-shaped cells had an average speed. Both fast cells and slow cells were characterized by a low differentiation potential, and average-moving cells were more effective in undergoing all three lineage differentiations. Furthermore, heterogeneity in single cell motility within a population correlated with the average-moving cells, and fast- and slow-moving cells tended toward homogeneity (i.e., a monotonous moving pattern). In conclusion, in vitro cell motility might be a useful tool to quickly characterize and distinguish the MSC population's differentiation potential before additional use. PMID:25473086

  5. [The potential financial impact of oral health problems in the families of preschool children].

    PubMed

    Ribeiro, Gustavo Leite; Gomes, Monalisa Cesarino; Lima, Kenio Costa de; Martins, Carolina Castro; Paiva, Saul Martins; Granville-Garcia, Ana Flávia

    2016-04-01

    The aim of the study was to evaluate the perception of parents/caregivers regarding the financial impact of oral health problems on the families of preschool children. A preschool-based, cross-sectional study was conducted with 834 preschool children in Campina Grande, Brazil. Parents/caregivers answered the Early Childhood Oral Health Impact Scale. "Financial impact" was the dependent variable. Questionnaires addressing socio-demographic variables, history of toothache and health perceptions were administered. Clinical exams were performed by three dentists previously calibrated (Kappa: 0.85-0.90). Descriptive statistics were performed, followed by logistic regression for complex samples (α = 5%). The frequency of financial impact due to oral health problems in preschool children was 7.7%. The following variables were significantly associated with financial impact: parental perception of child's oral health as poor, the interaction between history of toothache and absence of dental caries and the interaction between history of toothache and presence of dental caries. It is concluded that often parents/caregivers reported experiencing a financial impact due to seeking treatment late, mainly by the presence of toothache and complications of the clinical condition. PMID:27076020

  6. Identification of species-specific nuclear insertions of mitochondrial DNA (numts) in gorillas and their potential as population genetic markers

    PubMed Central

    Clark Nicholas, Jonathan; Wildschutte Julia, Vera Halo; DiMattio, Kelly; Jensen-Seaman, Michael Ignatius; Anthony, Nicola Mary

    2014-01-01

    The first hyper-variable region (HV1) of the mitochondrial control region (MCR) has been widely used as a molecular tool in population genetics, but inadvertent amplification of nuclear translocated copies of mitochondrial DNA (numts) in gorillas has compromised the use of mitochondrial DNA in population genetic studies. At least three putative classes (I, II, III) of gorilla-specific HV1 MCR numts have been uncovered over the past decade. However, the number, size and location of numt loci in gorillas and other apes are completely unknown. Furthermore, little work to date has assessed the utility of numts as candidate population genetic markers. In the present study, we screened Bacterial Artificial Chromosome (BAC) genomic libraries in the chimpanzee and gorilla to compare patterns of mitochondrial-wide insertion in both taxa. We conducted an intensive BLAST search for numts in the gorilla genome and compared the prevalence of numt loci originating from the MCR with other great ape taxa. Additional gorilla-specific MCR numts were retrieved either through BAC library screens or using an anchored-PCR (A-PCR) amplification using genomic DNA from five unrelated gorillas. Locus-specific primers were designed to identify numt insertional polymorphisms and evaluate their potential as population genetic markers. Mitochondrial-wide surveys of chimpanzee and gorilla BACs showed that the number of numts does not differ between these two taxa. However, MCR numts are more abundant in chimpanzees than in other great apes. We identified and mapped 67 putative gorilla-specific numts, including two that contain the entire HV1 domain, cluster with sequences from two numt classes (I, IIb) and will likely co-amplify with mitochondrial sequences using most published HV1 primers. However, phylogenetic analysis coupled with post-hoc analysis of mitochondrial variation can successfully differentiate nuclear sequences. Insertional polymorphisms were evident in three out of five numts

  7. Mitosis Is a Source of Potential Markers for Screening and Survival and Therapeutic Targets in Cervical Cancer

    PubMed Central

    Espinosa, Ana María; Alfaro, Ana; Roman-Basaure, Edgar; Guardado-Estrada, Mariano; Palma, Ícela; Serralde, Cyntia; Medina, Ingrid; Juárez, Eligia; Bermúdez, Miriam; Márquez, Edna; Borges-Ibáñez, Manuel; Muñoz-Cortez, Sergio; Alcántara-Vázquez, Avissai; Alonso, Patricia; Curiel-Valdez, José; Kofman, Susana; Villegas, Nicolas; Berumen, Jaime

    2013-01-01

    The effect of preventive human papillomavirus (HPV) vaccination on the reduction of the cervical cancer (CC) burden will not be known for 30 years. Therefore, it’s still necessary to improve the procedures for CC screening and treatment. The objective of this study was to identify and characterize cellular targets that could be considered potential markers for screening or therapeutic targets. A pyramidal strategy was used. Initially the expression of 8,638 genes was compared between 43 HPV16-positive CCs and 12 healthy cervical epitheliums using microarrays. A total of 997 genes were deregulated, and 21 genes that showed the greatest deregulation were validated using qRT-PCR. The 6 most upregulated genes (CCNB2, CDC20, PRC1, SYCP2, NUSAP1, CDKN3) belong to the mitosis pathway. They were further explored in 29 low-grade cervical intraepithelial neoplasias (CIN1) and 21 high-grade CIN (CIN2/3) to investigate whether they could differentiate CC and CIN2/3 (CIN2+) from CIN1 and controls. CCNB2, PRC1, and SYCP2 were mostly associated with CC and CDC20, NUSAP1, and CDKN3 were also associated with CIN2/3. The sensitivity and specificity of CDKN3 and NUSAP1 to detect CIN2+ was approximately 90%. The proteins encoded by all 6 genes were shown upregulated in CC by immunohistochemistry. The association of these markers with survival was investigated in 42 CC patients followed up for at least 42 months. Only CDKN3 was associated with poor survival and it was independent from clinical stage (HR = 5.9, 95%CI = 1.4–23.8, p = 0.01). CDKN3 and NUSAP1 may be potential targets for the development of screening methods. Nevertheless, further studies with larger samples are needed to define the optimal sensitivity and specificity. Inhibition of mitosis is a well-known strategy to combat cancers. Therefore, CDKN3 may be not only a screening and survival marker but a potential therapeutic target in CC. However, whether it’s indispensable for tumor growth remains to be

  8. Identification of species-specific nuclear insertions of mitochondrial DNA (numts) in gorillas and their potential as population genetic markers.

    PubMed

    Soto-Calderón, Iván Darío; Clark, Nicholas Jonathan; Wildschutte, Julia Vera Halo; DiMattio, Kelly; Jensen-Seaman, Michael Ignatius; Anthony, Nicola Mary

    2014-12-01

    The first hyper-variable region (HV1) of the mitochondrial control region (MCR) has been widely used as a molecular tool in population genetics, but inadvertent amplification of nuclear translocated copies of mitochondrial DNA (numts) in gorillas has compromised the use of mitochondrial DNA in population genetic studies. At least three putative classes (I, II, III) of gorilla-specific HV1 MCR numts have been uncovered over the past decade. However, the number, size and location of numt loci in gorillas and other apes are completely unknown. Furthermore, little work to date has assessed the utility of numts as candidate population genetic markers. In the present study, we screened Bacterial Artificial Chromosome (BAC) genomic libraries in the chimpanzee and gorilla to compare patterns of mitochondrial-wide insertion in both taxa. We conducted an intensive BLAST search for numts in the gorilla genome and compared the prevalence of numt loci originating from the MCR with other great ape taxa. Additional gorilla-specific MCR numts were retrieved either through BAC library screens or using an anchored-PCR (A-PCR) amplification using genomic DNA from five unrelated gorillas. Locus-specific primers were designed to identify numt insertional polymorphisms and evaluate their potential as population genetic markers. Mitochondrial-wide surveys of chimpanzee and gorilla BACs showed that the number of numts does not differ between these two taxa. However, MCR numts are more abundant in chimpanzees than in other great apes. We identified and mapped 67 putative gorilla-specific numts, including two that contain the entire HV1 domain, cluster with sequences from two numt classes (I, IIb) and will likely co-amplify with mitochondrial sequences using most published HV1 primers. However, phylogenetic analysis coupled with post-hoc analysis of mitochondrial variation can successfully differentiate nuclear sequences. Insertional polymorphisms were evident in three out of five numts

  9. Potential Use of Salivary Markers for Longitudinal Monitoring of Inflammatory Immune Responses to Vaccination

    PubMed Central

    Garssen, Johan; Sandalova, Elena

    2016-01-01

    Vaccination, designed to trigger a protective immune response against infection, is a trigger for mild inflammatory responses. Vaccination studies can address the question of inflammation initiation, levels, and resolution as well as its regulation for respective studied pathogens. Such studies largely based on analyzing the blood components including specific antibodies and cytokines were usually constrained by number of participants and volume of collected blood sample. Hence, blood-based studies may not be able to cover the full dynamic range of inflammation responses induced by vaccination. In this review, the potential of using saliva in addition to blood for studying the kinetics of inflammatory response studies was assessed. Saliva sampling is noninvasive and has a great potential to be used for studies aimed at analysing the magnitude, time course, and variance in immune responses, including inflammation after vaccination. Based on a literature survey of inflammatory biomarkers that can be determined in saliva and an analysis of how these biomarkers could help to understand the mechanisms and dynamics of immune reactivity and inflammation, we propose that the saliva-based approach might have potential to add substantial value to clinical studies, particularly in vulnerable populations such as infants, toddlers, and ill individuals. PMID:27022211

  10. 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/β-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

  11. A diagnostic molecular marker for zebra mussels (Dreissena polymorpha) and potentially co-occurring bivalves: mitochondrial COI.

    PubMed

    Baldwin, B S; Black, M; Sanjur, O; Gustafson, R; Lutz, R A; Vrijenhoek, R C

    1996-03-01

    We report diagnostic differences in the nucleotide sequences of a 710-bp fragment of the mitochondrial cytochrome c oxidase subunit I gene (COI) from the zebra mussel (Dreissena polymorpha) and potentially co-occurring bivalves: the quagga mussel (Dreissena bugensis); the Asiatic clam (Corbicula fluminea), the dark false mussel (Mytilopsis leucophaeata), and the wedge clam (Rangia cuneata). The COI sequence of the deep-water "profunda" phenotype of the quagga mussel was nearly identical to that of shallow-water quagga mussels. Restriction fragment length polymorphisms (RFLPs) in this portion of COI produced species-specific differences in fragment numbers and sizes that could be used as diagnostic markers to distinguish the free-living larvae produced by these bivalves. PMID:8869514

  12. SOCS3 tyrosine phosphorylation as a potential bio-marker for myeloproliferative neoplasms associated with mutant JAK2 kinases

    PubMed Central

    Elliott, Joanne; Suessmuth, Yvonne; Scott, Linda M.; Nahlik, Krystyna; McMullin, Mary Frances; Constantinescu, Stefan N.; Green, Anthony R.; Johnston, James A.

    2009-01-01

    JAK2 V617F, identified in the majority of patients with myeloproliferative neoplasms, tyrosine phosphorylates SOCS3 and escapes its inhibition. Here, we demonstrate that the JAK2 exon 12 mutants described in a subset of V617F-negative MPN cases, also stabilize tyrosine phosphorylated SOCS3. SOCS3 tyrosine phosphorylation was also observed in peripheral blood mononuclear cells and granulocytes isolated from patients with JAK2 H538QK539L or JAK2 F537-K539delinsL mutations. JAK kinase inhibitors, which effectively inhibited the proliferation of cells expressing V617F or K539L, also caused a dose-dependent reduction in both mutant JAK2 and SOCS3 tyrosine phosphorylation. We propose, therefore, that SOCS3 tyrosine phosphorylation may be a novel bio-marker of myeloproliferative neoplasms resulting from a JAK2 mutation and a potential reporter of effective JAK2 inhibitor therapy currently in clinical development. PMID:19229050

  13. A new glucosyl feruloyl quinic acid as a potential marker for roots and rhizomes of goldenseal, Hydrastis canadensis.

    PubMed

    McNamara, Catherine E; Perry, Nigel B; Follett, John M; Parmenter, Graeme A; Douglas, James A

    2004-11-01

    A new compound, 5-O-(4'-[beta-d-glucopyranosyl]-trans-feruloyl)quinic acid (GPFQ, 10), is reported from the medicinal plant goldenseal (Hydrastis canadensis). A new HPLC method is described and used to show that GPFQ is a potential marker for goldenseal roots (1.0% w/w) and rhizomes (2.3%). GPFQ was found at much lower levels in stems (<0.1%) and could not be detected in leaves. Neochlorogenic acid (9), which has not previously been reported from goldenseal, and chlorogenic acid (6) reached their highest levels in leaves (0.9% 9 and 0.5% 6). The main alkaloids, hydrastine (1) and berberine (2), were highest in rhizomes (2.8% 1 and 4.6% 2), but palmatine (5) was not found in genuine goldenseal. PMID:15568768

  14. Potential novel markers to discriminate between active and latent tuberculosis infection in Chinese individuals.

    PubMed

    Bai, Xue-juan; Liang, Yan; Yang, You-rong; Feng, Jin-dong; Luo, Zhan-peng; Zhang, Jun-Xian; Wu, Xue-qiong

    2016-02-01

    Latent tuberculosis infection (LTBI) constitutes the main reservoir for reactivation tuberculosis. The finding of potential biomarkers for differentiating between TB and LTBI is very necessary. In this study, the immunological characteristics and potential diagnostic utility of Rv2029c, Rv2628 and Rv1813c proteins were assessed. These three proteins stimulated PBMCs from ELISPOT-positive LTBI subjects produced higher levels of IFN-γ in comparison with TB patients and ELISPOT-negative healthy subjects (p<0.05). BCG vaccination and non-TB respiratory disease had little influence on the immunological responses of Rv2029c and Rv2628 proteins (p>0.05). The LTBI diagnostic performance of Rv2029c was higher than Rv2628 and Rv1813c by ROC evaluation. But Rv2628 had much higher specificity than Rv2029c in active TB patients and uninfected healthy subjects. The IgG level against Rv1813c was higher in the TB group than in LTBI and uninfected healthy subjects (p<0.05). These results suggest that T cell response to Rv2628 and antibody against Rv1813c might be applicable as biomarkers to distinguish TB from LTBI and uninfected individuals. PMID:26851588

  15. Identification of potential general markers of disease resistance in American oysters, Crassostrea virginica through gene expression studies.

    PubMed

    Nikapitiya, Chamilani; McDowell, Ian C; Villamil, Luisa; Muñoz, Pilar; Sohn, SaeBom; Gomez-Chiarri, Marta

    2014-11-01

    Several diseases have a significant impact on American oyster populations in the Atlantic coasts of North America. Knowledge about the responses of oysters to pathogenic challenge could help in identifying potential markers of disease resistance and biomarkers of the health status of an oyster population. A previous analysis of the transcriptome of resistant and susceptible American oysters in response to challenge with the bacterial pathogen Roseovarius crassostreae, as well as sequencing of suppression subtractive hybridization libraries from oysters challenged with the protozoan parasite Perkinsus marinus, provided a list of genes potentially involved in disease resistance or susceptibility. We investigated the patterns of inducible gene expression of several of these genes in response to experimental challenge with the oyster pathogens R. crassostreae, Vibrio tubiashii, and P. marinus. Oysters showing differential susceptibility to R. crassostreae demonstrated differential patterns of expression of genes coding for immune (serine protease inhibitor-1, SPI1) and stress-related (heat shock protein 70, HSP70; arginine kinase) proteins 30 days after challenge with this bacterial pathogen. Differential patterns of expression of immune (spi1, galectin and a matrix metalloproteinase) and stress-related (hsp70, histone H4, and arginine kinase) genes was observed in hemocytes from adult oysters challenged with P. marinus, but not with V. tubiashii. While levels of spi1 expression in hemocytes collected 8 and 21 days after P. marinus challenge were negatively correlated with parasite load in oysters tissues at the end of the challenge (62 days), levels of expression of hsp70 in hemocytes collected 1-day after challenge were positively correlated with oyster parasite load at 62 days. Our results confirm previous research on the role of serine protease inhibitor-1 in immunity and disease resistance in oysters. They also suggest that HSP70 and histone H4 could be used

  16. Potent and Orally Bioavailable Antiplatelet Agent, PLD-301, with the Potential of Overcoming Clopidogrel Resistance

    PubMed Central

    Chen, Jingyu; Wang, Michael Zhiyan

    2016-01-01

    PLD-301, a phosphate prodrug of clopidogrel thiolactone discovered by Prelude Pharmaceuticals with the aim to overcome clopidogrel resistance, was evaluated for its in vivo inhibitory effect on ADP-induced platelet aggregation in rats. The potency of PLD-301 was similar to that of prasugrel, but much higher than that of clopidogrel. The results of pharmacokinetic analysis showed that the oral bioavailability of clopidogrel thiolactone converted from PLD-301 was 4- to 5-fold higher than that of the one converted from clopidogrel, suggesting that in comparison with clopidogrel, lower doses of PLD-301 could be used clinically. In summary, PLD-301 presents a potent and orally bioavailable antiplatelet agent that might have some advantages over clopidogrel, such as overcoming clopidogrel resistance for CYP2C19-allele loss-of-function carriers, and lowering dose-related toxicity due to a much lower effective dose.

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

    PubMed Central

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

    1981-01-01

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

  18. Theta Burst Stimulation of the Cerebellum Modifies the TMS-Evoked N100 Potential, a Marker of GABA Inhibition

    PubMed Central

    2015-01-01

    Theta burst stimulation (TBS) of the cerebellum, a potential therapy for neurological disease, can modulate corticospinal excitability via the dentato-thalamo-cortical pathway, but it is uncertain whether its effects are mediated via inhibitory or facilitatory networks. The aim of this study was to investigate the effects of 30Hz cerebellar TBS on the N100 waveform of the TMS-evoked potential (TEP), a marker of intracortical GABAB-mediated inhibition. 16 healthy participants (aged 18–30 years; 13 right handed and 3 left handed) received 30Hz intermittent TBS (iTBS), continuous TBS (cTBS) or sham stimulation over the right cerebellum, in three separate sessions. The first 8 participants received TBS at a stimulus intensity of 80% of active motor threshold (AMT), while the remainder received 90% of AMT. Motor evoked potentials (MEP) and TEP were recorded before and after each treatment, by stimulating the first dorsal interosseus area of the left motor cortex. Analysis of the 13 right handed participants showed that iTBS at 90% of AMT increased the N100 amplitude compared to sham and cTBS, without significantly altering MEP amplitude. cTBS at 80% of active motor threshold decreased the N100 amplitude and cTBS overall reduced resting MEP amplitude. The study demonstrates effects of 30Hz cerebellar TBS on inhibitory cortical networks that may be useful for treatment of neurological conditions associated with dysfunctional intracortical inhibition. PMID:26529225

  19. Potential for use of retinoic acid as an oral vaccine adjuvant

    PubMed Central

    Mwanza-Lisulo, Mpala; Kelly, Paul

    2015-01-01

    Despite the heavy burden of diarrhoeal disease across much of the tropical world, only two diarrhoea-causing pathogens, cholera and rotavirus, are the target of commercially available vaccines. Oral vaccines are generally less immunogenic than the best parenteral vaccines, but the reasons for this are still debated. Over the past decade, several lines of evidence from work in experimental animals have suggested that all-trans retinoic acid (ATRA), a form of vitamin A which is highly transcriptionally active, can alter the homing receptor expression of T lymphocytes. Increased expression of α4β7 integrin and the chemokine receptor CCR9 following exposure to ATRA can be used to redirect T cells to the gut. Early work in human volunteers suggests that oral ATRA administration 1 h prior to dosing with oral typhoid vaccine can augment secretion of specific IgA against vaccine-derived lipopolysaccharide into gut secretions. In this review, we set out the rationale for using ATRA in this way and assess its likely applicability to vaccination programmes for protection of children in low-income countries from the considerable mortality caused by diarrhoeal disease. Comparison of recent work in experimental animals, non-human primates and men suggests that a more detailed understanding of ATRA dosage and kinetics will be important to taking forward translational work into human vaccinology. PMID:25964457

  20. 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

  1. Comparative protein profiles: potential molecular markers from spermatozoa of Acipenseriformes (Chondrostei, Pisces).

    PubMed

    Li, Ping; Hulak, Martin; Rodina, Marek; Sulc, Miroslav; Li, Zhi-Hua; Linhart, Otomar

    2010-12-01

    Sturgeon and paddlefish (Acipenseriformes), the source of roe consumed as caviar, are a unique and commercially valuable group of ancient fishes. In this study, comparative proteomics was used to analyze protein profiles of spermatozoa from five sturgeon species and one paddlefish: Siberian sturgeon (Acipenser baerii), sterlet (A. ruthenus), Russian sturgeon (A. gueldenstaedtii), starry sturgeon (A. stellatus), beluga (Huso huso), and Mississippi paddlefish (Polyodon spathula). Protein profiles of spermatozoa were determined by isoelectric focusing and two-dimensional electrophoresis (2-DE) high-resolution gels. The peptides, previously selected by 2-DE analysis as potentially species-specific, were obtained by "in-gel" tryptic digestion, followed by matrix-associated laser desorption/ionization time-of-flight/mass spectrometry (MALDI-TOF/MS). Among the 23 protein spots selected, 14 were identified as isoforms of enolase B present in all species, but with different isoelectric points or molecular mass. Exceptions were A. ruthenus and H. huso, species with a close phylogenetic relationship. Glycerol-3-phosphate dehydrogenase was detected exclusively in P. spathula. Phosphoglycerate kinase was detected only in A. ruthenus and H. huso, and 3 additional proteins (fructose bisphosphate aldolase A-2, glycogen phosphorylase type IV and glyceraldehyde-3-phosphate dehydrogenase) were found exclusively in A. gueldenstaedtii and H. huso. This study points to the application of proteomics for differential characterization and comparative studies of acipenseriform species at the molecular level. PMID:20869341

  2. Blood DNA methylation markers in potentially identified Chinese patients with hepatocellular carcinoma.

    PubMed

    Liu, Zongying; Yan, Haixiu; Zhang, Jinshu

    2016-07-01

    To determine whether blood DNA methylation is associated with hepatocellular carcinoma (HCC) for Chinese patients, we used genome-wide DNA methylation detection to access the blood samples of Chinese patients by Illumina Human methylation 450K arrays. Sixty potentially gene locis which had different methylated levels significantly among tumor and adjacent normal tissues would be tested in this study. A previous study was conducted in China communities and followed with 7 years. The DNA from white blood cells (WBC) from 192 patients with HCC and 215 matched controls were assayed in this study. The χ2 test was used to measure data to categorize variables and t -test was used to evaluate the different characteristics among groups. Besides, odds ratios (OR) and 95%CI was calculated for matching factors by conditional logistic regression models. We found that high methylation in WNK2 was related to increased risk of HCC, and high methylation in TPO were related to decreased risk of HCC. In our multivariable conditional logistic regression models, these results all exist. Those findings support the methylated changes of WNK2 and TPO may become a new detection index for HCC patients in clinical laboratory. However, the results should be replicated in additional prospective studies with lager samples. PMID:27592479

  3. A GENE SIGNATURE OF NON-HEALING VENOUS ULCERS: POTENTIAL DIAGNOSTIC MARKERS

    PubMed Central

    Charles, Carlos A.; Tomic-Canic, Marjana; Vincek, Vladimir; Nassiri, Mehdi; Stojadinovic, Olivera; Eaglstein, William H.; Kirsner, Robert S.

    2016-01-01

    Background Venous leg ulcers are responsible for more than half of all lower extremity ulcerations. Significant interest has been focused on understanding the physiologic basis upon which patients fail to heal with standard therapy. Objective This study uses complementary DNA microarray analysis of tissue samples from healing and non-healing venous leg ulcers to identify the genetic expression profiles from these dichotomous populations. Methods Ulcer size and chronicity, factors that have been identified as prognostic indicators for healing, were used to distribute venous leg ulcers as healing versus non-healing. Punch biopsy samples were obtained from the wound edge and wound bed of all venous leg ulcers. The top fifteen genes with differential expression greater than twofold between the two populations of wounds (p < 0.05) were reported. Results Significant differences were demonstrated in the expression of a diverse collection of genes, with particular differences demonstrated by genes coding for structural epidermal proteins, genes associated with hyperproliferation and tissue injury, as well as transcription factors. Limitations Small sample size may mitigate potential clinical implications of findings. Conclusions The genetic expression profiles displayed here may have implications for the development of novel therapies for chronic venous leg ulcers, and may also serve as prognostic indicators for wound healing. PMID:18718692

  4. Orphan nuclear receptor nurr1 as a potential novel marker for progression in human prostate cancer.

    PubMed

    Wang, Jian; Yang, Jing; Zou, Ying; Huang, Guo-Liang; He, Zhi-Wei

    2013-01-01

    A number of studies have indicated that Nurr1, which belongs to a novel class of orphan nuclear receptors (the NR4A family), is important for carcinogenesis. Here we investigated expression of Nurr1 protein in benign and malignant human prostate tissues and association with clinicopathologic features using immunohistochemical techniques. Moreover, we also investigated the ability of Nurr1 to influence proliferation, migration, invasion and apoptosis of human prostate cancer cells using small interfering RNA silencing. Immunohistochemical analysis revealed that the expression of Nurr1 protein was higher in prostate cancer tissues than in benign prostate tissue (P < 0.001), levels being positively correlated with tumor T classification (P = 0.003), N classification (P = 0.017), M classification (P = 0.011) and the Gleason score (P = 0.020) of prostate cancer patients. In vitro, silencing of endogenous Nurr1 attenuated cell proliferation, migration and invasion, and induced apoptosis of prostate cancer cells. These results suggest that Nurr1 may be used as an indicator for prostate cancer progression and be useful for novel potential therapeutic strategies. PMID:23679312

  5. Salivary Acetylcholinesterase Activity Is Increased in Parkinson's Disease: A Potential Marker of Parasympathetic Dysfunction

    PubMed Central

    Fedorova, Tatyana; Knudsen, Cindy Soendersoe; Mouridsen, Kim; Nexo, Ebba; Borghammer, Per

    2015-01-01

    Introduction. Decreased salivary flow and xerostomia are frequent findings in Parkinson's disease (PD), possibly caused by alterations in the parasympathetic tonus. Here we explore salivary acetylcholinesterase (AChE) activity as a potential biomarker in PD. Methods. We measured salivary flow, AChE activity, and total protein concentration in 30 PD patients and 49 healthy controls. We also performed exploratory correlation analyses with disease duration, motor symptom severity, autonomic complaints, and other nonmotor symptoms. Results. PD patients displayed significantly decreased salivary flow rate, significantly increased salivary AChE activity, and total protein concentration. Importantly, the AChE activity/total protein ratio was significantly increased in PD patients, suggesting that increased AChE activity cannot be explained solely by upconcentration of saliva. The Unified PD Rating Scale (UPDRS) score displayed significant correlation with total salivary protein (P = 0.002) and near-significant correlation with salivary flow (P = 0.07). Color vision test scores were also significantly correlated with AChE activity (P = 0.04) and total protein levels (P = 0.002). Conclusion. Salivary AChE activity is increased in PD patients compared to healthy controls. Future studies are needed to elucidate whether this parameter reflects the extent of neuronal damage and parasympathetic denervation in the salivary glands of PD patients. PMID:25767737

  6. Potential of carotenoids in aquatic yeasts as a phylogenetically reliable marker and natural colorant for aquaculture.

    PubMed

    Ueno, Ryohei; Hamada-Sato, Naoko; Ishida, Masami; Urano, Naoto

    2011-01-01

    Apart from Xanthophyllomyces dendrorhous, pink colony-forming yeasts have not been examined as a pigmentation source in captive animals. In this study, aquatic yeasts were screened with a view to abundances of carotenoids. Phylogenetic analyses of these caroetnoid-rich yeasts based on large subunit ribosomal RNA gene (LSU rDNA) partial sequences showed that all belonged to the order Sporidiobolales. Both the qualitative and the quantitative differences in carotenoids between the yeasts appeared to be consistent with their phylogenetic affiliations. This information might be useful in the selection of pigment-rich yeasts containing specific carotenoids from a large number of strains. We also found, for the first time, the potential of a pigment-rich Rhodotorula strain as a colorant for aquaculture. The integuments of tilapia and carp fed the alkali-treated cells of strain Rhodotorula dairenensis Sag 17 were pigmented after 3 months of cultivation. The fish integuments retained the yeast carotenes shortly after the start of feeding, and were converted to the fish-specific xanthophylls in vivo. PMID:21897034

  7. Endosialin expression in soft tissue sarcoma as a potential marker of undifferentiated mesenchymal cells

    PubMed Central

    Thway, Khin; Robertson, David; Jones, Robin L; Selfe, Joanna; Shipley, Janet; Fisher, Cyril; Isacke, Clare M

    2016-01-01

    Background: Soft tissue sarcomas are a group of neoplasms with differentiation towards mesenchymal tissue, many of which are aggressive and chemotherapy resistant. Histology and immunoprofiles often overlap with neoplasms of other lineages, and establishing an accurate histopathological diagnosis is crucial for correct management, and therapeutic stratification. The endosialin cell surface glycoprotein is predominantly expressed by stromal fibroblasts and pericytes in epithelial neoplasms; however, tumour cell expression has been reported in small series of sarcomas. Methods: We assessed endosialin expression by immunohistochemistry in a large set of 514 human soft tissue sarcomas. Results: Tumour cell endosialin expression was seen in 89% of undifferentiated pleomorphic sarcomas (104/117), 77% adult fibrosarcomas/spindle cell sarcomas (20/26), 62% synovial sarcomas (37/60), 51% leiomyosarcomas (94/185) and 31% rhabdomyosarcomas (39/126). Conclusions: Endosialin immunohistochemistry has potential to distinguish undifferentiated and poorly differentiated sarcomas from other poorly differentiated, non-mesenchymal neoplasms. A Phase II trial randomising patients with advanced sarcomas to receive chemotherapy with/without an endosialin therapeutic antibody has recently completed enrolment. Endosialin expression could be used to select patients for such clinical trials. Based on our results, patients with undifferentiated pleomorphic sarcoma may be particularly suitable for such a therapeutic approach. PMID:27434038

  8. Effects of a triphasic combination oral contraceptive containing norgestimate/ethinyl estradiol on biochemical markers of bone metabolism in young women with osteopenia secondary to hypothalamic amenorrhea.

    PubMed

    Grinspoon, S K; Friedman, A J; Miller, K K; Lippman, J; Olson, W H; Warren, M P

    2003-08-01

    This multicenter, double-blind, placebo-controlled, randomized study of 45 patients evaluated the short-term effects of an oral contraceptive [Ortho Tri-Cyclen, 180-250 micro g of norgestimate (NGM) and 35 microg of ethinyl estradiol (EE)] on biochemical markers of bone resorption, formation, and osteoprotegerin in young women (mean age +/- SD, 26.5 +/- 6.3 yr) with hypothalamic amenorrhea and osteopenia. Body fat, endocrine, and cognitive function were evaluated as secondary endpoints. Biomarkers of bone metabolism were measured at baseline and after three cycles of NGM/EE or placebo. There were significant decreases in mean values of N-telopeptide [mean (SD), -13.4 (13.4) vs. 1.2 (23.8) nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); P = 0.001] and deoxypyridinoline [-1.2 (2.9) vs. -0.5 (1.5) nmol deoxypyridinoline/mmol Cr; P = 0.021] as well as significant decreases in bone specific alkaline phosphatase [-5.1 (3.5) vs. 0.4 (3.1) ng/ml; P < 0.001], osteocalcin [-5.9 (3.6) vs. -2.9 (3.7); P = 0.016], and procollagen of type I propeptide [-35.2 (44.6) vs. -0.2 (30.0) ng/ml; P = 0.025], but not osteoprotegerin [0.39 (1.46) vs. -0.2 (0.49) pmol/liter; P = 0.397] in the NGM/EE vs. placebo group. There were no significant differences between groups with respect to changes in cognitive function, mood, body weight, body mass index, body fat, percentage of body fat, and all endocrine levels except FSH, [-3.7 (3.8) vs. -0.6 (2.1) IU/liter; P < 0.001, NGM/EE vs. placebo]. No serious adverse events were reported in either group. These results suggest that NGM/EE decreases bone turnover in osteopenic premenopausal women with hypothalamic amenorrhea. Further studies are needed to determine whether estrogen will increase bone density in this population. PMID:12915650

  9. Hydrogen emission in meteors as a potential marker for the exogenous delivery of organics and water

    NASA Technical Reports Server (NTRS)

    Jenniskens, Peter; Mandell, Avram M.

    2004-01-01

    We detected hydrogen Balmer-alpha (H(alpha)) emission in the spectra of bright meteors and investigated its potential use as a tracer for exogenous delivery of organic matter. We found that it is critical to observe the meteors with high enough spatial resolution to distinguish the 656.46 nm H(alpha) emission from the 657.46 nm intercombination line of neutral calcium, which was bright in the meteor afterglow. The H(alpha) line peak stayed in constant ratio to the atmospheric emissions of nitrogen during descent of the meteoroid. If all of the hydrogen originates in the Earth's atmosphere, the hydrogen atoms are expected to have been excited at T = 4400 K. In that case, we measured an H(2)O abundance in excess of 150 +/- 20 ppm at 80-90 km altitude (assuming local thermodynamic equilibrium in the air plasma). This compares with an expected <20 ppm from H(2)O in the gas phase. Alternatively, meteoric refractory organic matter (and water bound in meteoroid minerals) could have caused the observed H(alpha) emission, but only if the line is excited in a hot T approximately 10000 K plasma component that is unique to meteoric ablation vapor emissions such as Si(+). Assuming that the Si(+) lines of the Leonid spectrum would need the same hot excitation conditions, and a typical [H]/[C] = 1 in cometary refractory organics, we calculated an abundance ratio [C]/[Si] = 3.9 +/- 1.4 for the dust of comet 55P/Tempel-Tuttle. This range agreed with the value of [C]/[Si] = 4.4 measured for comet 1P/Halley dust. Unless there is 10 times more water vapor in the upper atmosphere than expected, we conclude that a significant fraction of the hydrogen atoms in the observed meteor plasma originated in the meteoroid.

  10. Suprabasin, a novel epidermal differentiation marker and potential cornified envelope precursor.

    PubMed

    Park, Geon Tae; Lim, Susan E; Jang, Shyh-Ing; Morasso, Maria I

    2002-11-22

    The suprabasin gene is a novel gene expressed in mouse and human differentiating keratinocytes. We identified a partial cDNA encoding suprabasin using a suppression subtractive hybridization method between the proliferative basal and differentiating suprabasal populations of the mouse epidermis. A 3' gene-specific probe hybridized to transcripts of 0.7- and 2.2-kb pairs on Northern blots with specific detection in differentiated keratinocytes of stratified epithelia. The mouse gene was mapped to chromosome 7 by fluorescence in situ hybridization. This region is syntenic to human chromosome band 19q13.1, which contained the only region in the data bases with homology to the mouse suprabasin sequence. During embryonic mouse development, suprabasin mRNA was detected at day 15.5, coinciding with epidermal stratification. Suprabasin was detected in the suprabasal layers of the epithelia in the tongue, stomach, and epidermis. Differentiation of cultured primary epidermal keratinocytes with 0.12 mm Ca(2+) or 12-O-tetradecanoylphorbol-13-acetate treatment resulted in the induction of suprabasin. The 2.2-kb cDNA transcript encodes a protein of 72 kDa with a predicted isoelectric point of 6.85. The translated sequence has an amino-terminal domain, a central domain composed of repeats rich in glycine and alanine, and a carboxyl-terminal domain. The alternatively spliced 0.7-kb transcript encodes a smaller protein that shares the NH(2)- and COOH-terminal regions but lacks the repeat domain region. Cross-linking experiments indicate that suprabasin is a substrate for transglutaminase 2 and 3 activity. Altogether, these results indicate that the suprabasin protein potentially plays a role in the process of epidermal differentiation. PMID:12228223

  11. Predictive value of bovine follicular components as markers of oocyte developmental potential.

    PubMed

    Matoba, Satoko; Bender, Katrin; Fahey, Alan G; Mamo, Solomon; Brennan, Lorraine; Lonergan, Patrick; Fair, Trudee

    2014-01-01

    The follicle is a unique micro-environment within which the oocyte can develop and mature to a fertilisable gamete. The aim of this study was to investigate the ability of a panel of follicular parameters, including intrafollicular steroid and metabolomic profiles and theca, granulosa and cumulus cell candidate gene mRNA abundance, to predict the potential of bovine oocytes to develop to the blastocyst stage in vitro. Individual follicles were dissected from abattoir ovaries, carefully ruptured under a stereomicroscope and the oocyte was recovered and individually processed through in vitro maturation, fertilisation and culture. The mean (±s.e.m.) follicular concentrations of testosterone (62.8±4.8 ngmL(-1)), progesterone (616.8±31.9 ngmL(-1)) and oestradiol (14.4±2.4 ngmL(-1)) were not different (P>0.05) between oocytes that formed (competent) or failed to form (incompetent) blastocysts. Principal-component analysis of the quantified aqueous metabolites in follicular fluid showed differences between oocytes that formed blastocysts and oocytes that degenerated; l-alanine, glycine and l-glutamate were positively correlated and urea was negatively correlated with blastocyst formation. Follicular fluid associated with competent oocytes was significantly lower in palmitic acid (P=0.023) and total fatty acids (P=0.031) and significantly higher in linolenic acid (P=0.036) than follicular fluid from incompetent oocytes. Significantly higher (P<0.05) transcript abundance of LHCGR in granulosa cells, ESR1 and VCAN in thecal cells and TNFAIP6 in cumulus cells was associated with competent compared with incompetent oocytes. PMID:23514964

  12. Tissue microarray-based study of hepatocellular carcinoma validating SPIB as potential clinical prognostic marker.

    PubMed

    Ho, Yi-Jung; Lin, Yueh-Min; Huang, Yen-Chi; Yeh, Kun-Tu; Lin, Liang-In; Lu, Jeng-Wei

    2016-01-01

    Currently, the prognostic significance of SPIB protein overexpression in human hepatocellular carcinoma (HCC) is unclear. The aim of the present study was to investigate the level of SPIB expression in human HCC in order to determine possible correlations between SPIB expression and clinicopathological findings. The expression of SPIB proteins was detected using immunohistochemical staining in commercial multiple-tissue microarrays as a means of examining expression profiles in patients. Using online biomarker validation tool SurvExpress, we focused on the correlation between SPIB overexpression and survival as well as relapse-free survival (RFS). Results show that SPIB protein expression levels were significantly higher in colon, liver, and stomach tumors than in non-tumor tissues (p<0.05). SPIB overexpression in patients with HCC was also significantly higher than that of the normal samples (p<0.001). Among patients with liver disease, SPIB protein expression levels differ significantly according to the stage of liver disease, specifically between stages I, II, and III of HCC (p<0.05). SPIB expression was also shown to be significantly correlated with age (p=0.046) and histological grade (p=0.027). Furthermore, the SurvExpress analysis suggested that high SPIB and KI-67 mRNA expression were significantly associated with the poor survival of patients with HCC (p<0.05). Our results indicate that cross-talk in the expression of SPIB and KI-67 may be associated with poor prognosis and may potentially serve as a clinical prognostic indicator of HCC. This is the first time that such an association has been reported. PMID:26610895

  13. Telomerase Activity as a Potential Diagnostic Marker for Triage of Abnormal Pap Smears

    PubMed Central

    Ault, Kevin A.; Allen, Heather K.; Phillips, Stacia L.; Bridget Zimmerman, M.; Klingelhutz, Aloysius J.

    2008-01-01

    Objectives To determine whether there is an association between high levels of telomerase and premalignant cervical disease and to provide a preliminary analysis of telomerase activity as a potential triage strategy. Materials and Methods Premenopausal women were invited to participate in the study during routine gynecologic visits as well as visits where colposcopy was performed. Samples were taken from the cervix using a broom device and placed in cold phosphate-buffered saline. A total of 92 samples were evaluated. Cells were counted and lysed, and a semi-quantitative measure of telomerase activity was determined using a commercially available telomerase enzyme-linked immunosorbent assay kit. The presence of human papillomavirus (HPV) types 16 and 18 was assessed by polymerase chain reaction analysis. One-way analysis of variance was used to test for the association of telomerase activity with cytology, HPV type 16 or 18 status, and colposcopy and/or biopsy findings. Results When telomerase levels were analyzed according to Pap smear results, there were no differences among four groups of cytology findings (normal, atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion). When colposcopy and/or biopsy results were considered, significantly higher levels of telomerase were detected in cervical intraepithelial neoplasia (CIN) 2,3 samples than in normal Pap smear samples and CIN 1 samples (p = .035). There was no significant difference in telomerase levels between samples that tested positive for HPV type 16 or 18 and those that did not (p = .111). Conclusions Telomerase levels were significantly higher in cytologic samples from women with biopsy-proven CIN 2,3 than in samples from women with normal cytology results or CIN 1. These results warrant larger studies to determine whether telomerase activity may be a useful triage tool for abnormal cytologic findings. PMID:15870530

  14. Hydrogen emission in meteors as a potential marker for the exogenous delivery of organics and water.

    PubMed

    Jenniskens, Peter; Mandell, Avram M

    2004-01-01

    We detected hydrogen Balmer-alpha (H(alpha)) emission in the spectra of bright meteors and investigated its potential use as a tracer for exogenous delivery of organic matter. We found that it is critical to observe the meteors with high enough spatial resolution to distinguish the 656.46 nm H(alpha) emission from the 657.46 nm intercombination line of neutral calcium, which was bright in the meteor afterglow. The H(alpha) line peak stayed in constant ratio to the atmospheric emissions of nitrogen during descent of the meteoroid. If all of the hydrogen originates in the Earth's atmosphere, the hydrogen atoms are expected to have been excited at T = 4400 K. In that case, we measured an H(2)O abundance in excess of 150 +/- 20 ppm at 80-90 km altitude (assuming local thermodynamic equilibrium in the air plasma). This compares with an expected <20 ppm from H(2)O in the gas phase. Alternatively, meteoric refractory organic matter (and water bound in meteoroid minerals) could have caused the observed H(alpha) emission, but only if the line is excited in a hot T approximately 10000 K plasma component that is unique to meteoric ablation vapor emissions such as Si(+). Assuming that the Si(+) lines of the Leonid spectrum would need the same hot excitation conditions, and a typical [H]/[C] = 1 in cometary refractory organics, we calculated an abundance ratio [C]/[Si] = 3.9 +/- 1.4 for the dust of comet 55P/Tempel-Tuttle. This range agreed with the value of [C]/[Si] = 4.4 measured for comet 1P/Halley dust. Unless there is 10 times more water vapor in the upper atmosphere than expected, we conclude that a significant fraction of the hydrogen atoms in the observed meteor plasma originated in the meteoroid. PMID:15104908

  15. Molecular signature of salivary gland tumors: potential use as diagnostic and prognostic marker.

    PubMed

    Fonseca, Felipe Paiva; Sena Filho, Marcondes; Altemani, Albina; Speight, Paul M; Vargas, Pablo Agustin

    2016-02-01

    Salivary gland tumors are a highly heterogeneous group of lesions with diverse microscopic appearances and variable clinical behavior. The use of clinical and histological parameters to predict patient prognosis and survival rates has been of limited utility, and the search for new biomarkers that could not only aid in a better understanding of their pathogenesis but also be reliable auxiliaries for prognostic determination and useful diagnostic tools has been performed in the last decades with very exciting results. Hence, gene rearrangements such as CRTC1-MAML2 in mucoepidermoid carcinomas have shown excellent specificity, and more than that, it has been strongly correlated with low-grade tumors and consequently with an increased survival rate and better prognosis of patients affected by neoplasms carrying this translocation. Moreover, MYB-NFIB and EWSR1-ATF1 gene fusions were shown to be specifically found in cases of adenoid cystic carcinomas and hyalinizing clear cell carcinomas, respectively, in the context of salivary gland tumors, becoming reliable diagnostic tools for these entities and potential therapeutic targets for future therapeutic protocols. Finally, the identification of ETV6-NTRK3 in cases previously diagnosed as uncommon acinic cell carcinomas, cystadenocarcinomas, and adenocarcinomas not otherwise specified led to the characterization of a completely new and now widely accepted entity, including, therefore, mammary analogue secretory carcinoma in the list of well-recognized salivary gland carcinomas. Thus, further molecular investigations of salivary gland tumors are warranted, and the recognition of other genetic abnormalities can lead to the acknowledgment of new entities and the acquirement of reliable biomarkers. PMID:25990369

  16. Disordered porphyrin metabolism: a potential biological marker for autism risk assessment.

    PubMed

    Heyer, Nicholas J; Echeverria, Diana; Woods, James S

    2012-04-01

    Autism (AUT) is a complex neurodevelopmental disorder that, together with Asperger's syndrome and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), comprises the expanded classification of autistic spectrum disorder (ASD). The heterogeneity of ASD underlies the need to identify biomarkers or clinical features that can be employed to identify meaningful subtypes of ASD, define specific etiologies, and inform intervention and treatment options. Previous studies have shown that disordered porphyrin metabolism, manifested principally as significantly elevated urinary concentrations of pentacarboxyl (penta) and coproporphyrins, is commonly observed among some children with ASD. Here, we extend these observations by specifically evaluating penta and coproporphyrins as biological indicators of ASD among 76 male children comprising 30 with validated AUT, 14 with PDD-NOS, and 32 neurotypical (NT) controls. ASD children (AUT and PDD-NOS) had higher mean urinary penta (P < 0.006) and copro (P < 0.006) concentrations compared with same-aged NT children, each characterized by a number of extreme values. Using Receiver Operating Characteristic curve analysis, we evaluated the sensitivity and specificity of penta, copro, and their combined Z-scores in ASD detection. The penta sensitivity was 30% for AUT and 36% for PDD-NOS, with 94% specificity. The copro sensitivity was 33% and 14%, respectively, with 94% specificity. The combined Z-score measure had 33% and 21% sensitivity for AUT and PDD-NOS, respectively, with 100% specificity. These findings demonstrate that porphyrin measures are strong predictors of both AUT and PDD-NOS, and support the potential clinical utility of urinary porphyrin measures for identifying a subgroup of ASD subjects in whom disordered porphyrin metabolism may be a salient characteristic. PMID:22298513

  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 50μm to 110μm. In general, thermal injury is more pronounced using fiber tips in contact mode compared to the focused laser beam. In conclusion the results reveal that even the low power diode pumped Er:YAG laser is an appropriate tool for oral surgery.

  18. 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

  19. Impairment of mesenchymal stem cells derived from oral leukoplakia

    PubMed Central

    Zhang, Zhihui; Song, Jiangyuan; Han, Ying; Mu, Dongdong; Su, Sha; Ji, Xiaoli; Liu, Hongwei

    2015-01-01

    Oral leukoplakia is one of the common precancerous lesions in oral mucosa. To compare the biological characteristics and regenerative capacities of mesenchymal stem cells (MSCs) from oral leukoplakia (epithelial hyperplasia and dysplasia) and normal oral mucosa, MSCs were isolated by enzyme digestion. Then these cells were identified by the expression of MSC related markers, STRO-1, CD105 and CD90, with the absent for the hematopoietic stem cell marker CD34 by flow cytometric detection. The self-renewal ability of MSCs from oral leukoplakia was enhanced, while the multipotent differentiation was descended, compared with MSCs from normal oral mucosa. Fibrin gel was used as a carrier for MSCs transplanted into immunocompromised mice to detect their regenerative capacity. The regenerative capacities of MSCs from oral leukoplakia became impaired partly. Collagen IV (Col IV) and matrix metalloproteinases-9 (MMP-9) were selected to analyze the potential mechanism for the functional changes of MSCs from oral leukoplakia by immunochemical and western blot analysis. The expression of Col IV was decreased and that of MMP-9 was increased by MSCs with the progression of oral leukoplakia, especially in MSCs from epithelial dysplasia. The imbalance between regenerative and metabolic self-regulatory functions of MSCs from oral leukoplakia may be related to the progression of this premalignant disorder. PMID:26617710

  20. Growth Differentiation Factor-15 (GDF-15) is a potential marker of radiation response and radiation sensitivity.

    PubMed

    Sándor, Nikolett; Schilling-Tóth, Boglárka; Kis, Enikő; Benedek, Anett; Lumniczky, Katalin; Sáfrány, Géza; Hegyesi, Hargita

    2015-11-01

    We have investigated the importance of GDF-15 (secreted cytokine belonging to the TGF-β superfamily) in low and high dose radiation-induced cellular responses. A telomerase immortalized human fibroblast cell line (F11hT) was used in the experiments. A lentiviral system encoding small hairpin RNAs (shRNA) was used to establish GDF-15 silenced cells. Secreted GDF-15 levels were measured in culture medium by ELISA. Cell cycle analysis was performed by flow cytometry. The experiments demonstrated that in irradiated human fibroblasts GDF-15 expression increased with dose starting from 100mGy. Elevated GDF-15 expression was not detected in bystander cells. The potential role of GDF-15 in radiation response was investigated by silencing GDF-15 in immortalized human fibroblasts with five different shRNA encoded in lentiviral vectors. Cell lines with considerably reduced GDF-15 levels presented increased radiation sensitivity, while a cell line with elevated GDF-15 was more radiation resistant than wild type cells. We have investigated how the reduced GDF-15 levels alter the response of several known radiation inducible genes. In F11hT-shGDF-15 cells the basal expression level of CDKN1A was unaltered relative to F11hT cells, while GADD45A and TGF-β1 mRNA levels were slightly higher, and TP53INP1 was considerably reduced. The radiation-induced expression of TP53INP1 was lower in the silenced than in wild type fibroblast cells. Cell cycle analysis indicated that radiation-induced early G2/M arrest was abrogated in GDF-15 silenced cells. Moreover, radiation-induced bystander effect was less pronounced in GDF-15 silenced fibroblasts. In conclusion, the results suggest that GDF-15 works as a radiation inducible radiation resistance increasing factor in normal human fibroblast cells, acts by regulating the radiation-induced transcription of several genes and might serve as a radiation-induced early biomarker in exposed cells. PMID:26520384

  1. Novel Peptide Marker Corresponding to Salivary Protein gSG6 Potentially Identifies Exposure to Anopheles Bites

    PubMed Central

    Poinsignon, Anne; Cornelie, Sylvie; Mestres-Simon, Montserrat; Lanfrancotti, Alessandra; Rossignol, Marie; Boulanger, Denis; Cisse, Badara; Sokhna, Cheikh; Arcà, Bruno; Simondon, François; Remoue, Franck

    2008-01-01

    Background In order to improve malaria control, and under the aegis of WHO recommendations, many efforts are being devoted to developing new tools for identifying geographic areas with high risk of parasite transmission. Evaluation of the human antibody response to arthropod salivary proteins could be an epidemiological indicator of exposure to vector bites, and therefore to risk of pathogen transmission. In the case of malaria, which is transmitted only by anopheline mosquitoes, maximal specificity could be achieved through identification of immunogenic proteins specific to the Anopheles genus. The objective of the present study was to determine whether the IgG response to the Anopheles gambiae gSG6 protein, from its recombinant form to derived synthetic peptides, could be an immunological marker of exposure specific to Anopheles gambiae bites. Methodology/Principal Findings Specific IgG antibodies to recombinant gSG6 protein were observed in children living in a Senegalese area exposed to malaria. With the objective of optimizing Anopheles specificity and reproducibility, we designed five gSG6-based peptide sequences using a bioinformatic approach, taking into consideration i) their potential antigenic properties and ii) the absence of cross-reactivity with protein sequences of other arthropods/organisms. The specific anti-peptide IgG antibody response was evaluated in exposed children. The five gSG6 peptides showed differing antigenic properties, with gSG6-P1 and gSG6-P2 exhibiting the highest antigenicity. However, a significant increase in the specific IgG response during the rainy season and a positive association between the IgG level and the level of exposure to Anopheles gambiae bites was significant only for gSG6-P1. Conclusions/Significance This step-by-step approach suggests that gSG6-P1 could be an optimal candidate marker for evaluating exposure to Anopheles gambiae bites. This marker could be employed as a geographic indicator, like remote sensing

  2. Genetic Structure and Inferences on Potential Source Areas for Bactrocera dorsalis (Hendel) Based on Mitochondrial and Microsatellite Markers

    PubMed Central

    Shi, Wei; Kerdelhué, Carole; Ye, Hui

    2012-01-01

    Bactrocera dorsalis (Diptera: Tephritidae) is mainly distributed in tropical and subtropical Asia and in the Pacific region. Despite its economic importance, very few studies have addressed the question of the wide genetic structure and potential source area of this species. This pilot study attempts to infer the native region of this pest and its colonization pathways in Asia. Combining mitochondrial and microsatellite markers, we evaluated the level of genetic diversity, genetic structure, and the gene flow among fly populations collected across Southeast Asia and China. A complex and significant genetic structure corresponding to the geographic pattern was found with both types of molecular markers. However, the genetic structure found was rather weak in both cases, and no pattern of isolation by distance was identified. Multiple long-distance dispersal events and miscellaneous host selection by this species may explain the results. These complex patterns may have been influenced by human-mediated transportation of the pest from one area to another and the complex topography of the study region. For both mitochondrial and microsatellite data, no signs of bottleneck or founder events could be identified. Nonetheless, maximal genetic diversity was observed in Myanmar, Vietnam and Guangdong (China) and asymmetric migration patterns were found. These results provide indirect evidence that the tropical regions of Southeast Asia and southern coast of China may be considered as the native range of the species and the population expansion is northward. Yunnan (China) is a contact zone that has been colonized from different sources. Regions along the southern coast of Vietnam and China probably served to colonize mainly the southern region of China. Southern coastal regions of China may also have colonized central parts of China and of central Yunnan. PMID:22615898

  3. Epigenetic regulation of CD271, a potential cancer stem cell marker associated with chemoresistance and metastatic capacity

    PubMed Central

    LI, SULAN; YUE, DONGLI; CHEN, XINFENG; WANG, LIPING; LI, JIEYAO; PING, YU; GAO, QUN; WANG, DAN; ZHANG, TENGFEI; LI, FENG; YANG, LI; HUANG, LAN; ZHANG, YI

    2015-01-01

    Cancer stem cells (CSCs) are considered to be the cause of tumor initiation, metastasis and recurrence. Additionally, CSCs are responsible for the failure of chemotherapy and radiotherapy. The isolation and identification of CSCs is crucial for facilitating the monitoring, therapy or prevention of cancer. We aimed to identify esophageal squamous cell carcinoma (ESCC) stem-like cells, the epigenetic mechanism and identify novel biomarkers for targeting ESCC CSCs. Sixty-three paired ESCC tissues and adjacent non-cancerous tissues were included in this study. CD271, which was identified as the CSC marker for melanoma, was assessed using quantitative PCR (qPCR). Using flow cytometry, we isolated CD271+ cells comprising 7.5% of cancer cells from the KYSE70 cell line. Sphere formation and anchorage-independent growth were analyzed in CD271+ and CD271− cancer cells, respectively. qPCR was used to detect stem-related genes and CCK-8 was performed to analyze the sensitivity to chemotherapy in the two groups. Bisulfite genomic sequencing was used to analyze the methylation status. CD271 expression was significantly higher in ESCC tissues than in adjacent non-cancerous tissues. Compared with CD271− cancer cells, CD271+ cancer cells showed a higher ability of sphere and colony formation, a high level expression of stem-related gene, and resistance to chemotherapy. The expression of CD271 was induced by a demethylation agent. In conclusion, CD271+ ESCC cells possess stem-like properties. CD271 can potentially act as a prognostic marker for ESCC, whose expression is regulated epigenetically. PMID:25351876

  4. The stem cell marker prominin-1/CD133 interacts with vascular endothelial growth factor and potentiates its action.

    PubMed

    Adini, Avner; Adini, Irit; Ghosh, Kaustabh; Benny, Ofra; Pravda, Elke; Hu, Ron; Luyindula, Dema; D'Amato, Robert J

    2013-04-01

    Prominin-1, a pentaspan transmembrane protein, is a unique cell surface marker commonly used to identify stem cells, including endothelial progenitor cells and cancer stem cells. However, recent studies have shown that prominin-1 expression is not restricted to stem cells but also occurs in modified forms in many mature adult human cells. Although prominin-1 has been studied extensively as a stem cell marker, its physiological function of the protein has not been elucidated. We investigated prominin-1 function in two cell lines, primary human endothelial cells and B16-F10 melanoma cells, both of which express high levels of prominin-1. We found that prominin-1 directly interacts with the angiogenic and tumor survival factor vascular endothelial growth factor (VEGF) in both the primary endothelial cells and the melanoma cells. Knocking down prominin-1 in the endothelial cells disrupted capillary formation in vitro and decreased angiogenesis in vivo. Similarly, tumors derived from prominin-1 knockdown melanoma cells had a reduced growth rate in vivo. Further, melanoma cells with knocked down prominin-1 had diminished ability to interact with VEGF, which was associated with decreased bcl-2 protein levels and increased apoptosis. In vitro studies with soluble prominin-1 showed that it stabilized dimer formation of VEGF164, but not VEGF121. Taken together, our findings support the notion that prominin-1 plays an active role in cell growth through its ability to interact and potentiate the anti-apoptotic and pro-angiogenic activities of VEGF. Additionally, prominin-1 promotes tumor growth by supporting angiogenesis and inhibiting tumor cell apoptosis. PMID:23150059

  5. Genetic diversity analysis of cyanogenic potential (CNp) of root among improved genotypes of cassava using simple sequence repeat markers.

    PubMed

    Moyib, O K; Mkumbira, J; Odunola, O A; Dixon, A G

    2012-12-01

    Cyanogenic potential (CNp) of cassava constitutes a serious problem for over 500 million people who rely on the crop as their main source of calories. Genetic diversity is a key to successful crop improvement for breeding new improved variability for target traits. Forty-three improved genotypes of cassava developed by International Institute of Tropical Agriculture (ITA), Ibadan, were characterized for CNp trait using 35 Simple Sequence.Repeat (SSR) markers. Essential colorimetry picric test was used for evaluation of CNp on a color scale of 1 to 14. The CNp scores obtained ranged from 3 to 9, with a mean score of 5.48 (+/- 0.09) based on Statistical Analysis System (SAS) package. TMS M98/ 0068 (4.0 +/- 0.25) was identified as the best genotype with low CNp while TMS M98/0028 (7.75 +/- 0.25) was the worst. The 43 genotypes were assigned into 7 phenotypic groups based on rank-sum analysis in SAS. Dissimilarity analysis representatives for windows generated a phylogenetic tree with 5 clusters which represented hybridizing groups. Each of the clusters (except 4) contained low CNp genotypes that could be used for improving the high CNp genotypes in the same or near cluster. The scatter plot of the genotypes showed that there was little or no demarcation for phenotypic CNp groupings in the molecular groupings. The result of this study demonstrated that SSR markers are powerful tools for the assessment of genetic variability, and proper identification and selection of parents for genetic improvement of low CNp trait among the IITA cassava collection. PMID:23678653

  6. 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

  7. 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

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

    PubMed

    Palombo, Enzo A

    2011-01-01

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

  9. Lipid-based oral delivery systems for skin deposition of a potential chemopreventive DIM derivative: characterization and evaluation.

    PubMed

    Boakye, Cedar H A; Patel, Ketan; Patel, Apurva R; Faria, Henrique A M; Zucolotto, Valtencir; Safe, Stephen; Singh, Mandip

    2016-10-01

    The objective of this study was to explore the oral route as a viable potential for the skin deposition of a novel diindolylmethane derivative (DIM-D) for chemoprevention activity. Various lipid-based oral delivery systems were optimized and compared for enhancing DIM-D's oral bioavailability and skin deposition. Preformulation studies were performed to evaluate the log P and solubility of DIM-D. Microsomal metabolism, P-glycoprotein efflux, and caco-2 monolayer permeability of DIM-D were determined. Comparative evaluation of the oral absorption and skin deposition of DIM-D-loaded various lipid-based formulations was performed in rats. DIM-D showed pH-dependent solubility and a high log P value. It was not a strong substrate of microsomal degradation and P-glycoprotein. SMEDDs comprised of medium chain triglycerides, monoglycerides, and kolliphor-HS15 (36.70 ± 0.42 nm). SNEDDs comprised of long chain triglycerides, cremophor RH40, labrasol, and TPGS (84.00 ± 14.14 nm). Nanostructured lipid carriers (NLC) consisted of compritol, miglyol, and surfactants (116.50 ± 2.12 nm). The blank formulations all showed >70 % cell viability in caco-2 cells. Differential Scanning Calorimetry confirmed the amorphization of DIM-D within the lipid matrices while Atomic Force Microscopy showed particle size distribution similar to the dynamic light scattering data. DIM-D also showed reduced permeation across caco-2 monolayer that was enhanced (p < 0.05) by SNEDDs in comparison to SMEDDs and NLC. Fabsolute for DIM-D SNEDDs, SMEDDs, and NLC was 0.14, 0.04, and 0.007, respectively. SNEDDs caused 53.90, 11.32, and 15.08-fold more skin deposition of DIM-D than the free drug, SMEDDs, and NLC, respectively, at 2 h following oral administration and shows a viable potential for use in skin cancer chemoprevention. Graphical Abstract ᅟ. PMID:27405772

  10. Readily restoring freeze-dried probilosomes as potential nanocarriers for enhancing oral delivery of cyclosporine A.

    PubMed

    Guan, Peipei; Lu, Yi; Qi, Jianping; Wu, Wei

    2016-08-01

    Formulating vesicular nanocarriers into dried precursors so as to overcome the drawbacks associated with liquid formulations is challengeable due to low efficiency of restoration. In this study, bilosomes interiorly thickened with gelatin (G-BLs) was evaluated for the ability to withstand freeze-drying stress and enhanced oral bioavailability of a model drug, cyclosporine A (CyA). The restoration efficiency of freeze-dried pro-G-BLs is investigated by comparing the particle size distribution, entrapment efficiency and morphology of the bilosomes before and after freeze-drying. Particle size and polydispersity index (PI) of pro-G-BLs after restoration was similar to that before freeze-drying, whereas freeze-dried bilosomes without gelatin thickening (pro-BLs) show irreversible damage and aggregation along with significantly increased particle size and PI after restoration. Entrapment efficiency of pro-G-BLs remains as high as 83.7%, in sharp contrast with 66.7% for pro-BLs. Pharmacokinetics in beagle dogs show improved absorption of CyA in pro-G-BLs as compared to pro-BLs, G-BLs and microemulsion-based Sandimmun Neoral(®). The relative oral bioavailability of CyA-loaded pro-G-BLs, pro-BLs and G-BLs was 165.2%, 123.5% and 130.1%, respectively, with Neoral(®) as the reference. It is concluded that interior thickening with gelatin significantly enhanced the stability against freeze-drying stress, which as a result improves the restoring efficiency and oral bioavailability. PMID:27085046

  11. Proteomics of stress responses in wheat and barley—search for potential protein markers of stress tolerance

    PubMed Central

    Kosová, Klára; Vítámvás, Pavel; Prášil, Ilja T.

    2014-01-01

    Wheat (Triticum aestivum; T. durum) and barley (Hordeum vulgare) agricultural production is severely limited by various abiotic and biotic stress factors. Proteins are directly involved in plant stress response so it is important to study proteome changes under various stress conditions. Generally, both abiotic and biotic stress factors induce profound alterations in protein network covering signaling, energy metabolism (glycolysis, Krebs cycle, ATP biosynthesis, photosynthesis), storage proteins, protein metabolism, several other biosynthetic pathways (e.g., S-adenosylmethionine metabolism, lignin metabolism), transport proteins, proteins involved in protein folding and chaperone activities, other protective proteins (LEA, PR proteins), ROS scavenging enzymes as well as proteins affecting regulation of plant growth and development. Proteins which have been reported to reveal significant differences in their relative abundance or posttranslational modifications between wheat, barley or related species genotypes under stress conditions are listed and their potential role in underlying the differential stress response is discussed. In conclusion, potential future roles of the results of proteomic studies in practical applications such as breeding for an enhanced stress tolerance and the possibilities to test and use protein markers in the breeding are suggested. PMID:25566285

  12. Identification of potential markers and sensitive tissues for low or high salinity stress in an intertidal mud crab (Macrophthalmus japonicus).

    PubMed

    Nikapitiya, Chamilani; Kim, Won-Seok; Park, Kiyun; Kwak, Ihn-Sil

    2014-12-01

    Macrophthalmus japonicus is an intertidal mud crab is an ecologically important species in Korea, can tolerate a wide range of natural and anthropogenic stressors. Environmental changes especially salinity cause physiological stress to the marine habitats. Differential gene transcription of M. japonicus tissues provided information about tissue specific responses against salinity. Five potential genes were identified and their transcription levels were determined quantitatively comparison to seawater (SW: 31 ± 1 psu) in M. japonicus gills and hepatopancreas after exposed them to different salinities. Ecdysteroid receptor (Mj-EcR), trypsin (Mj-Tryp), arginine kinase (Mj-AK), lipopolysaccharide and β-1,3-glucan binding protein (Mj-LGBP) and peroxinectin (Mj-Prx) in hepatopancreas up-regulated against different salinities. In contrast, the gills, Mj-EcR, Mj-Tryp and Mj-AK showed late up-regulated responses to 40 psu compared to SW. All genes except Mj-LGBP showed up regulation in the gills as time dependent manner. These genes can be considered as potential markers to assess responses in salinity changes. This study suggests hepatopancreas is a suitable tissue for transcriptional, biochemical and physiological responses analysis on M. japonicus in low and high salinity stress. PMID:25240977

  13. Stroma derived COL6A3 is a potential prognosis marker of colorectal carcinoma revealed by quantitative proteomics

    PubMed Central

    Chen, Sun-Xia; Wang, Xiao-Qing; Cui, Shu-Jian; Liu, Xiao-Hui; Jiang, Ying-Hua; Wang, Jie; Zhang, Yang; Yang, Peng-Yuan; Liu, Feng

    2015-01-01

    Colorectal cancer (CRC) represents the third most common cancer in males and second in females worldwide. Here, we performed a quantitative 8-plex iTRAQ proteomics analysis of the secreted proteins from five colonic fibroblast cultures and three colon cancer epithelial cell lines. We identified 1114 proteins at 0% FDR, including 587 potential secreted proteins. We further recognized 116 fibroblast-enriched proteins which were significantly associated with cell movement, angiogenesis, proliferation and wound healing, and 44 epithelial cell-enriched proteins. By interrogation of Oncomine database, we found that 20 and 8 fibroblast-enriched proteins were up- and downregulated in CRC, respectively. Western blots confirmed the fibroblast-specific secretion of filamin C, COL6A3, COL4A1 and spondin-2. Upregulated mRNA and stroma expression of COL6A3 in CRC, which were revealed by Oncomine analyses and tissue-microarray-immunohistochemistry, indicated poor prognosis. COL6A3 expression was significantly associated with Dukes stage, T stage, stage, recurrence and smoking status. Circulating plasma COL6A3 in CRC patients was upregulated significantly comparing with healthy peoples. Receiver operating characteristic curve analysis revealed that COL6A3 has better predictive performance for CRC with an area under the curve of 0.885 and the best sensitivity/specificity of 92.9%/81.3%. Thus we demonstrated that COL6A3 was a potential diagnosis and prognosis marker of CRC. PMID:26338966

  14. Moisture sorption as a potential condition marker for historic silks: noninvasive determination by near-infrared spectroscopy.

    PubMed

    Zhang, Xiaomei; Wyeth, Paul

    2007-02-01

    Given their ephemeral nature, the preservation of historic silks can be problematic. Rapid, on-site condition monitoring would offer significant benefits to conservators and museum curators concerned with continued access to collections. In this paper, near-infrared spectroscopy (NIR) is investigated as a noninvasive approach to the characterization of silk fabrics and particularly for determining the moisture content of silks as a potential age-related marker. Bands within the NIR spectrum of silk are assigned to contributions from water and the silk fibroin polymer. The water bands may be deconvolved to show separate contributions from bound and structural water. When silk is exposed to deuterium oxide, the water OH NIR bands are rapidly lost. The accompanying changes in the amide-related NIR absorptions reflect differential accessibility of regions within the semi-crystalline fibroin aggregate. NIR spectra were recorded while silk was maintained at a range of relative humidity; complementary gravimetry provided absolute reference data for moisture sorption. A single spectral parameter, the intensity of the water combination band, is sufficient to indicate the relative moisture content of silk and allows distinction of unaged and heat, light, and humidity aged silks. The results confirm that NIR has significant potential for on-site studies at collections in support of the preservation and access of our silk heritage. PMID:17331315

  15. Stroma derived COL6A3 is a potential prognosis marker of colorectal carcinoma revealed by quantitative proteomics.

    PubMed

    Qiao, Jie; Fang, Cai-Yun; Chen, Sun-Xia; Wang, Xiao-Qing; Cui, Shu-Jian; Liu, Xiao-Hui; Jiang, Ying-Hua; Wang, Jie; Zhang, Yang; Yang, Peng-Yuan; Liu, Feng

    2015-10-01

    Colorectal cancer (CRC) represents the third most common cancer in males and second in females worldwide. Here, we performed a quantitative 8-plex iTRAQ proteomics analysis of the secreted proteins from five colonic fibroblast cultures and three colon cancer epithelial cell lines. We identified 1114 proteins at 0% FDR, including 587 potential secreted proteins. We further recognized 116 fibroblast-enriched proteins which were significantly associated with cell movement, angiogenesis, proliferation and wound healing, and 44 epithelial cell-enriched proteins. By interrogation of Oncomine database, we found that 20 and 8 fibroblast-enriched proteins were up- and downregulated in CRC, respectively. Western blots confirmed the fibroblast-specific secretion of filamin C, COL6A3, COL4A1 and spondin-2. Upregulated mRNA and stroma expression of COL6A3 in CRC, which were revealed by Oncomine analyses and tissue-microarray-immunohistochemistry, indicated poor prognosis. COL6A3 expression was significantly associated with Dukes stage, T stage, stage, recurrence and smoking status. Circulating plasma COL6A3 in CRC patients was upregulated significantly comparing with healthy peoples. Receiver operating characteristic curve analysis revealed that COL6A3 has better predictive performance for CRC with an area under the curve of 0.885 and the best sensitivity/specificity of 92.9%/81.3%. Thus we demonstrated that COL6A3 was a potential diagnosis and prognosis marker of CRC. PMID:26338966

  16. 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

  17. Microsatellite markers for the endangered Roanoke logperch, Percina rex (Percidae) and their potential utility for other darter species

    USGS Publications Warehouse

    Dutton, D.J.; Roberts, J.H.; Angermeier, P.L.; Hallerman, E.M.

    2008-01-01

    The Roanoke logperch (Percina rex Jordan and Evermann), an endangered fish, occurs in only six watersheds in the Roanoke and Chowan river drainages of Virginia, USA. The species' population genetic structure is poorly known. We developed 16 microsatellite markers that were reliably scorable and polymorphic P. rex. Markers were also screened in seven other darter species of the genus Percina. Most markers exhibited successful amplification and polymorphism in several species. These markers may therefore prove useful for population genetic studies in other darters, a diverse but highly imperiled group. ?? 2008 The Authors.

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

    PubMed

    Hsu, Mei-Ju; Hung, Shan-Ling

    2013-06-01

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

  19. 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

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

    PubMed

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

    2015-09-01

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

  1. 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

  2. Microsatellite Markers of Willow Species and Characterization of 11 Polymorphic Microsatellites for Salix eriocephala (Salicaceae), a Potential Native Species for Biomass Production in Canada

    PubMed Central

    Lauron-Moreau, Aurélien; Pitre, Frédéric E.; Brouillet, Luc; Labrecque, Michel

    2013-01-01

    Biomass produced from dedicated plantations constitutes a source of renewable energy and is expected to play an important role in several countries in the coming decades. The cultivation of woody crops such as willows therefore raises several environmental issues. In North America, several native willows are potentially interesting for biomass producers. Willow trees are diverse but few species used for environmental applications have been the object of molecular genetic studies. Based on the sequenced poplar genome, 24 microsatellite markers were assayed on five native North American willow species: Salix amygdaloides, S. discolor, S. eriocephala, S. interior and S. nigra. Polymorphic microsatellite markers were used to characterize the allele data on the shrub Salix eriocephala, a North American species with economic potential. Eleven markers amplified and confirmed the potential of this species. Analysis of samples from six populations in eastern Canada showed that all markers were variable as well as polymorphic in at least one population. The number of alleles per locus ranged from 1 to 9 (mean 2.95) and showed that these microsatellite markers can be used to assess genetic diversity of North American willow species. PMID:27137372

  3. 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

  4. 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

  5. The chloroplast psbK-psbI intergenic region, a potential genetic marker for broad sectional relationships in Anthurium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nuclear and chloroplast genetic markers have been extensively used for plant identification and molecular taxonomy studies. The efficacy of genetic markers to be used as DNA barcodes is under constant evaluation and improvement, with identification of new barcodes that provide greater resolution an...

  6. Potential of ordered mesoporous silica for oral delivery of poorly soluble drugs.

    PubMed

    Vialpando, Monica; Martens, Johan A; Van den Mooter, Guy

    2011-08-01

    The use of ordered mesoporous silica is one of the more recent and rapidly developing formulation techniques for enhancing the solubility of poorly water-soluble drugs. Their large surface area and pore volume make ordered mesoporous silica materials excellent candidates for efficient drug loading and rapid release. While this new approach offers many promising advantages, further research is still necessary to elucidate the molecular mechanisms and to improve our scientific insight into the behavior of this system. In this review, the significant developments to date are presented and research challenges highlighted. Aspects of downstream processability are discussed in view of their special bulk powder properties and unique pore architecture. Lastly, perspectives for successful oral dosage form development are presented. PMID:22833866

  7. Source localization of an event-related potential marker of executive attention following mild traumatic brain injury.

    PubMed

    Rogers, Jeffrey M; Donnelly, James; Wilson, Peter H

    2015-10-21

    Recent research suggests that intact performance on an executive attention task after mild traumatic brain injury (mTBI) reflects functional adaptation within neural networks, rather than recovery of premorbid modes of information processing. However, it is unclear whether this compensation includes the recruitment of alternative neural processing resources. The current study used source localization analysis to determine the location and timing of activated brain areas involved in the generation of an event-related potential (ERP) component marker of executive attention in 10 adults with mTBI and in 10 matched healthy controls. In both groups the cerebral sources of the late processing negativity component of the ERP waveform elicited during the Paced Auditory Serial Addition Task were localized to the left ventrolateral prefrontal cortex and right dorsal anterior cingulate cortex. Timing of the dipole moments was consistent with previous reports of the relative contributions of subregions of the frontal cortex critically involved in aspects of executive attention control. Finally, whereas abnormal intensity of ERP activation has recently been related to the achievement of normal levels of performance after mTBI, abnormal sources of cerebral activation do not appear to be a feature of the compensatory response. PMID:26302255

  8. Xanthurenic Acid Activates mGlu2/3 Metabotropic Glutamate Receptors and is a Potential Trait Marker for Schizophrenia

    PubMed Central

    Fazio, Francesco; Lionetto, Luana; Curto, Martina; Iacovelli, Luisa; Cavallari, Michele; Zappulla, Cristina; Ulivieri, Martina; Napoletano, Flavia; Capi, Matilde; Corigliano, Valentina; Scaccianoce, Sergio; Caruso, Alessandra; Miele, Jessica; De Fusco, Antonio; Di Menna, Luisa; Comparelli, Anna; De Carolis, Antonella; Gradini, Roberto; Nisticò, Robert; De Blasi, Antonio; Girardi, Paolo; Bruno, Valeria; Battaglia, Giuseppe; Nicoletti, Ferdinando; Simmaco, Maurizio

    2015-01-01

    The kynurenine pathway of tryptophan metabolism has been implicated in the pathophysiology of psychiatric disorders, including schizophrenia. We report here that the kynurenine metabolite, xanturenic acid (XA), interacts with, and activates mGlu2 and mGlu3 metabotropic glutamate receptors in heterologous expression systems. However, the molecular nature of this interaction is unknown, and our data cannot exclude that XA acts primarily on other targets, such as the vesicular glutamate transporter, in the CNS. Systemic administration of XA in mice produced antipsychotic-like effects in the MK-801-induced model of hyperactivity. This effect required the presence of mGlu2 receptors and was abrogated by the preferential mGlu2/3 receptor antagonist, LY341495. Because the mGlu2 receptor is a potential drug target in the treatment of schizophrenia, we decided to measure serum levels of XA and other kynurenine metabolites in patients affected by schizophrenia. Serum XA levels were largely reduced in a large cohort of patients affected by schizophrenia, and, in patients with first-episode schizophrenia, levels remained low after 12 months of antipsychotic medication. As opposed to other kynurenine metabolites, XA levels were also significantly reduced in first-degree relatives of patients affected by schizophrenia. We suggest that lowered serum XA levels might represent a novel trait marker for schizophrenia. PMID:26643205

  9. A Potential Epigenetic Marker Mediating Serum Folate and Vitamin B12 Levels Contributes to the Risk of Ischemic Stroke

    PubMed Central

    Keat Wei, Loo; Sutherland, Heidi; Au, Anthony; Camilleri, Emily; Haupt, Larisa M.; Gan, Siew Hua; Griffiths, Lyn R.

    2015-01-01

    Stroke is a multifactorial disease that may be associated with aberrant DNA methylation profiles. We investigated epigenetic dysregulation for the methylenetetrahydrofolate reductase (MTHFR) gene among ischemic stroke patients. Cases and controls were recruited after obtaining signed written informed consents following a screening process against the inclusion/exclusion criteria. Serum vitamin profiles (folate, vitamin B12, and homocysteine) were determined using immunoassays. Methylation profiles for CpGs A and B in the MTHFR gene were determined using a bisulfite-pyrosequencing method. Methylation of MTHFR significantly increased the susceptibility risk for ischemic stroke. In particular, CpG A outperformed CpG B in mediating serum folate and vitamin B12 levels to increase ischemic stroke susceptibility risks by 4.73-fold. However, both CpGs A and B were not associated with serum homocysteine levels or ischemic stroke severity. CpG A is a potential epigenetic marker in mediating serum folate and vitamin B12 to contribute to ischemic stroke. PMID:25705649

  10. Investigation and Sensory Characterization of 1,4-Cineole: A Potential Aromatic Marker of Australian Cabernet Sauvignon Wine.

    PubMed

    Antalick, Guillaume; Tempère, Sophie; Šuklje, Katja; Blackman, John W; Deloire, Alain; de Revel, Gilles; Schmidtke, Leigh M

    2015-10-21

    This work reports the quantitation and sensory characterization of 1,4-cineole in red wine for the first time. A headspace-solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) method was developed to quantitate 1,4-cineole and 1,8-cineole in 104 commercial Australian red wines. 1,4-Cineole was detected in all of the wines analyzed, with concentrations ranging from 0.023 to 1.6 μg/L. An important varietal effect was observed, with concentrations of 1,4-cineole in Cabernet Sauvignon wines (mean of 0.6 ± 0.3 μg/L) significantly higher than in Shiraz (0.07 ± 0.04 μg/L) and Pinot Noir (0.2 ± 0.2 μg/L) wines. Regional variations of both cineole isomer concentrations have been measured between wines originating from different Australian regions. Sensory studies demonstrated that the addition of 0.54 μg/L 1,4-cineole in a Cabernet Sauvignon wine, to produce a final concentration of 0.63 μg/L, was perceived significantly by a sensory panel (p < 0.05). Descriptive analyses revealed that 1,4-cineole and 1,8-cineole may contribute to the hay, dried herbs, and blackcurrant aromas reported in Australian Cabernet Sauvignon wines and may be potential markers of regional typicality of these wines. PMID:26434979

  11. Rhoptry protein 47 gene sequence: A potential novel genetic marker for population genetic studies of Toxoplasma gondii.

    PubMed

    Wang, Jin-Lei; Li, Ting-Ting; Li, Zhong-Yuan; Huang, Si-Yang; Ning, Hong-Rui; Zhu, Xing-Quan

    2015-07-01

    Toxoplasma gondii, an obligate intracellular parasite, is able to infect many animal species and humans, and can cause toxoplasmosis of the host. In this study, we examined sequence variation in rhoptry protein 47 (ROP47) gene among T. gondii isolates originating from different hosts and geographical regions. The entire genome region of the ROP47 gene was amplified and sequenced, and phylogenetic relationship was reconstructed using maximum parsimony (MP), maximum likelihood (ML) and neighbor-joining (NJ), based on the ROP47 gene sequences. The results of sequence alignments showed that all ROP47 gene sequences were 396 bp in length. There were 19 variable nucleotide positions in the coding region, resulted in 16 amino acid substitutions (12.21%) among all examined T. gondii strains and the existence of polymorphic restriction sites for endonucleases SacI and AflIII, allowing the differentiation of the three major clonal lineage types I, II and III by PCR-RFLP. Phylogenetic analysis of ROP47 gene sequences showed that three major clonal lineage types I, II and III were clustered differently, consistent with PCR-RFLP results. These results suggest that ROP47 gene sequence may represent a potential novel genetic marker for population genetic studies of T. gondii isolates. PMID:25862398

  12. Trisomy 8 Acute Myeloid Leukemia Analysis Reveals New Insights of DNA Methylome with Identification of HHEX as Potential Diagnostic Marker.

    PubMed

    Saied, Marwa H; Marzec, Jacek; Khalid, Sabah; Smith, Paul; Molloy, Gael; Young, Bryan D

    2015-01-01

    Trisomy 8 acute myeloid leukemia (AML) is the commonest numerical aberration in AML. Here we present a global analysis of trisomy 8 AML using methylated DNA immunoprecipitation-sequencing (MeDIP-seq). The study is based on three diagnostic trisomy 8 AML and their parallel relapse status in addition to nine non-trisomic AML and four normal bone marrows (NBMs). In contrast to non-trisomic DNA samples, trisomy 8 AML showed a characteristic DNA methylation distribution pattern because an increase in the frequency of the hypermethylation signals in chromosome 8 was associated with an increase in the hypomethylation signals in the rest of the chromosomes. Chromosome 8 hypermethylation signals were found mainly in the CpG island (CGI) shores and interspersed repeats. Validating the most significant differentially methylated CGI (P = 7.88 × 10(-11)) identified in trisomy 8 AML demonstrated a specific core region within the gene body of HHEX, which was significantly correlated with HHEX expression in both diagnostic and relapse trisomy 8 AMLs. Overall, the existence of extra chromosome 8 was associated with a global impact on the DNA methylation distribution with identification of HHEX gene methylation as a potential diagnostic marker for trisomy 8 AML. PMID:25674022

  13. Recombinant VirB5 protein as a potential serological marker for the diagnosis of bovine brucellosis.

    PubMed

    Tan, Wei; Wang, Xiu-ran; Nie, Ying; Wang, Chong; Cheng, Li-qing; Wang, Xiao-cen; Zhang, Rui; Yan, Guang-mou

    2012-06-01

    The molecular tag vaccine against Brucella abortus and serological testing are the main methods of prevention of brucellosis used currently. They can discriminate vaccinated animals and humans from those naturally infected. In this study, we constructed a gene deletion mutant strain, B. abortus S19 virB5 with a molecular tag. Recombinant VirB5 was expressed and purified for evaluation as a diagnostic reagent for bovine brucellosis. In total, 400 sera samples were tested using a VirB5 antigen-based enzyme-linked immunosorbent assay (ELISA) and the results were compared with those of the standard tube agglutination test (SAT). This showed that the sensitivity was 88.2%, specificity was 97.8% and accuracy was 94.8%. Recombinant VirB5 could also be used to discriminate B. abortus-infected mice from mice infected with the B. abortus S19 virB5 mutant strain. It was concluded that recombinant VirB5 could be used as a potential antigen and serological marker for the diagnosis of bovine brucellosis. PMID:22662340

  14. The mitochondrial genome of Euphausia superba (Prydz Bay) (Crustacea: Malacostraca: Euphausiacea) reveals a novel gene arrangement and potential molecular markers.

    PubMed

    Shen, Xin; Wang, Haiqing; Ren, Jianfeng; Tian, Mei; Wang, Minxiao

    2010-02-01

    Euphausiid krill are dominant organisms in the zooplankton population and play a central role in marine ecosystems. In this paper, we described the gene organization, gene rearrangement and codon usage in the mitochondrial genome of Euphausia superba Dana 1852 (sampling from Prydz Bay, PB). The mitochondrial genome of E. superba is more than 15,498 bp in length (partial non-coding region was not determined). Translocation of four tRNAs (trnL ( 1 ), trnL ( 2 ), trnW and trnI) and duplication of one tRNA (trnN) were founded in the mitochondrial genome of E. superba when comparing its genome with the pancrustacean ground pattern. To investigate the phylogenetic relationship within Malacostraca, phylogenetic trees based on currently available malacostracan mitochondrial genomes were built with the maximum likelihood and the Bayesian models. All analyses based on nucleotide and amino acid data strongly support the monophyly of Stomatopoda, Penaeidae, Caridea, and Brachyura, which is consistent with previous research. However, the taxonomic position of Euphausiacea within Malacostraca is unstable. From comparing the mitochondrial genome between E. superba (PB) and E. superba (sampling from Weddell Sea, WS), we found that nad2 gene contains maximal variation with 61 segregating sites, following by nad5 gene which has 12 segregating sites. Thus, nad2 and nad5 genes may be used as potential molecular markers to study the inherit diversity among different E. superba groups, which would be helpful to the exploitation and management of E. superba resources. PMID:19578978

  15. 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 β-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 ± 31 nm size with narrow size distribution (0.21 ± 0.07 PDI) and high zeta potential (-32.07 ± 4.58 mV). 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 μg/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

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

    PubMed

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

    2014-07-20

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

  17. 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 μg/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

  18. 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

  19. Quantum dots based potential-resolution dual-targets electrochemiluminescent immunosensor for subtype of tumor marker and its serological evaluation.

    PubMed

    Liu, Xuan; Jiang, Hui; Fang, Yuan; Zhao, Wei; Wang, Nianyue; Zang, Guizhen

    2015-09-15

    The identification of subtypes of known tumor markers is of great importance for clinical diagnosis but still a great challenge in novel detection methodologies with simple operation and acceptable sensitivity. This work for the first time reported a quantum dots (QDs) based potential-resolved electrochemiluminescent (ECL) immunosensor to realize simultaneous detection of dual targets. Because of different surface microstructures, dimercaptosuccinic acid stabilized CdTe (DMSA-CdTe) QDs and TiO2 nanoparticles-glutathione stabilized CdTe (TiO2-GSH-CdTe) QDs composites showed a large difference of ECL peak potential (∼360 mV), which provided an access for potential-resolution detection. The ECL emission on indium tin oxide electrodes showed consistent strength during the cyclic scan, and intensity data were collected at -0.89 V and -1.25 V (vs Ag/AgCl) for DMSA-CdTe QDs and TiO2-GSH-CdTe QDs composites, respectively. The interface modification procedures of immunosensor construction were characterized by atomic force microscopy. The portion of Lens culinaris lectin affiliated isoform of alpha fetoprotein (AFP), AFP-L3%, in total AFP, is recently a novel criteria showing even higher sensitivity and specificity than AFP at the early stage of cancer. Combined with the enzyme cyclic amplification strategy, linear ranges for AFP-L3 and AFP dual-targets detection were 3.24 pg mL(-1)-32.4 ng mL(-1) and 1.0 pg mL(-1)-20 ng mL(-1), with limits of detection of 3.24 pg mL(-1) and 1.0 pg mL(-1), respectively. Compared with clinical detection data, the calculated portion of AFP-L3% by as-prepared immunosensor showed acceptable accuracy. These results open a new avenue for facile and rapid multiple-components detection based on the nano-ECL technique and provide a new clinical diagnosis platform for HCC. PMID:26291342

  20. Potential role of differentially expressed lncRNAs in the pathogenesis of oral squamous cell carcinoma.

    PubMed

    Zhang, Shanchuan; Tian, Lili; Ma, Penghua; Sun, Qiang; Zhang, Kai; GuanchaoWang; Liu, Hongchen; Xu, Baohua

    2015-10-01

    Long non-coding RNAs (lncRNAs) have recently attracted more attention about the role in a broad range of biological processes and complex cancers. We aimed to identify differentially expressed lncRNAs that play an important role in the pathogenesis of oral squamous cell carcinoma (OSCC). Microarray data GSE25099 consisting of 57 samples from patients with OSCC and 22 normal samples were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) and lncRNAs were identified between OSCC samples and control using samr package in R and noncoder software. Co-expression network was constructed for lncRNAs and candidate target DEGs, followed by functional and pathway enrichment analysis using the Database for Annotation, Visualization and Integrated Discovery online tool. OSCC-related genes were screened by Genetic-Association-DB-Database analysis, and then protein-protein interaction (PPI) network construction of OSCC-related and co-expressed genes. Bioinformatic analysis revealed that there were 998 DEGs and 160 differentially expressed lncRNAs between OSCC and normal control. We found LOC100130547, FTH1P3, PDIA3F and GTF2IRD2P1 targeted most of DEGs. Predicted targets-related functional annotation showed significant changes in inflammation-related functions and Toll-like receptor signaling pathway. By further conducting PPI network with lncRNA co-expressed DEGs, we found that OSCC-associated genes including MMP1 (matrix metallopeptidase), MMP3, MMP9, PLAU (plasminogen activator, urokinase) and IL8 (interleukin 8) were targeted by FTH1P3, PDIA3F and GTF2IRD2P1. Our results indicate that lncRNAs FTH1P3, PDIA3F and GTF2IRD2P1 may responsible for progression and metastasis of OSCC via targeting MMP1, MMP3, MMP9, PLAU and IL8 which are key regulators of tumorigenesis. PMID:26276270

  1. PAR6, A Potential Marker for the Germ Cells Selected to Form Primordial Follicles in Mouse Ovary

    PubMed Central

    Wen, Jing; Zhang, Hua; Li, Ge; Mao, Guanping; Chen, Xiufen; Wang, Jianwei; Guo, Meng; Mu, Xinyi; Ouyang, Hong; Zhang, Meijia; Xia, Guoliang

    2009-01-01

    Partitioning-defective proteins (PAR) are detected to express mainly in the cytoplast, and play an important role in cell polarity. However, we showed here that PAR6, one kind of PAR protein, was localized in the nuclei of mouse oocytes that formed primordial follicles during the perinatal period, suggesting a new role of PAR protein. It is the first time we found that, in mouse fetal ovaries, PAR6 appeared in somatic cell cytoplasm and fell weak when somatic cells invaded germ cell cysts at 17.5 days post coitus (dpc). Meanwhile, the expression of PAR6 was observed in cysts, and became strong in the nuclei of some germ cells at 19.5 dpc and all primordial follicular oocytes at 3 day post parturition (dpp), and then obviously declined when the primordial follicles entered the folliculogenic growth phase. During the primordial follicle pool foundation, the number of PAR6 positive germ cells remained steady and was consistent with that of formed follicles at 3 dpp. There were no TUNEL (apoptosis examination) positive germ cells stained with PAR6 at any time studied. The number of follicles significantly declined when 15.5 dpc ovaries were treated with the anti-PAR6 antibody and PAR6 RNA interference. Carbenoxolone (CBX, a known blocker of gap junctions) inhibited the expression of PAR6 in germ cells and the formation of follicles. Our results suggest that PAR6 could be used as a potential marker of germ cells for the primordial follicle formation, and the expression of PAR6 by a gap junction-dependent process may contribute to the formation of primordial follicles and the maintenance of oocytes at the diplotene stage. PMID:19809506

  2. Gross cystic disease fluid protein 15 in stratum corneum is a potential marker of decreased eccrine sweating for atopic dermatitis.

    PubMed

    Kamiya, Koji; Sakabe, Jun-Ichi; Yamaguchi, Hayato; Suzuki, Takahiro; Yatagai, Tsuyoshi; Aoshima, Masahiro; Ito, Taisuke; Tokura, Yoshiki

    2015-01-01

    It is well known that eccrine sweating is attenuated in patients with atopic dermatitis (AD). We have reported by using proteome analysis that gross cystic disease fluid protein 15 (GCDFP15), a substance secreted from eccrine sweat glands, is decreased in tape-stripped stratum corneum (SC) samples from AD patients. The aim of this study was to evaluate GCDFP15 production by eccrine glands with SC samples and to assess sweating in AD. SC samples were obtained from 51 healthy control (HC) and 51 AD individuals. Sweat samples were from 18 HC and 12 AD subjects. GCDFP15 was quantified by ELISA. By immunohistochemistry, the expression of GCDFP15 in eccrine glands was examined in normal and AD skin specimens. To identify GCDFP15-producing cells, double immunofluorescence staining for GCDFP15 and S100 protein was performed in frozen sections. To address the mechanism underlying the decreased eccrine sweating in AD patients, we examined the expression of cholinergic receptor M3 (CHRM3), a receptor for acetylcholine-induced sweating, in eccrine sweat glands. The amounts of GCDFP15 in the SC extracts were significantly lower in AD than HC (P < 0.0001). The sweat samples from AD patients also had lower levels of GCDFP15 concentration (P < 0.05). Immunohistochemistry showed positive GCDFP15 staining in the eccrine gland secretory cells and the ductal and acrosyringial lumen in normal skin, but AD lacked clear staining. Immunofluorescence staining revealed that GCDFP15 was co-expressed with S100 protein, suggesting that the clear cell of eccrine glands produces GCDFP15. Finally, we found that the expression of CHRM3 was depressed in AD, suggesting contribution to the low sweating. The SC of AD patients contains a low amount of GCDFP15 due to both low sweating and low GCDFP15 concentration in the sweat. GCDFP15 in SC is a potential marker for dysregulated sweating in AD. PMID:25919462

  3. Plasmodium falciparum Gametocyte-Specific Antibody Profiling Reveals Boosting through Natural Infection and Identifies Potential Markers of Gametocyte Exposure.

    PubMed

    Skinner, Jeff; Huang, Chiung-Yu; Waisberg, Michael; Felgner, Philip L; Doumbo, Ogobara K; Ongoiba, Aissata; Kayentao, Kassoum; Traore, Boubacar; Crompton, Peter D; Williamson, Kim C

    2015-11-01

    Malaria elimination efforts would benefit from vaccines that block transmission of Plasmodium falciparum gametocytes from humans to mosquitoes. A clear understanding of gametocyte-specific antibody responses in exposed populations could help determine whether transmission-blocking vaccines (TBV) would be boosted by natural gametocyte exposure, and also inform the development of serologic tools to monitor gametocyte exposure in populations targeted for malaria elimination. To this end, plasma was collected from Malian children and adults before and after the 6-month malaria season and probed against a microarray containing 1,204 P. falciparum proteins. Using publicly available proteomic data, we classified 91 proteins as gametocyte specific and 69 as proteins not expressed by gametocytes. The overall breadth and magnitude of gametocyte-specific IgG responses increased during the malaria season, although they were consistently lower than IgG responses to nongametocyte antigens. Notably, IgG specific for the TBV candidates Pfs48/45 and Pfs230 increased during the malaria season. In addition, IgGs specific for the gametocyte proteins Pfmdv1, Pfs16, PF3D7_1346400, and PF3D7_1024800 were detected in nearly all subjects, suggesting that seroconversion to these proteins may be a sensitive indicator of gametocyte exposure, although further studies are needed to determine the specificity and kinetics of these potential serologic markers. These findings suggest that TBV-induced immunity would be boosted through natural gametocyte exposure, and that antibody responses to particular antigens may reliably indicate gametocyte exposure. PMID:26283330

  4. Expression level of chromodomain Y (CDY): potential marker for prediction of sperm recovery in non-obstructive azoospermia

    PubMed Central

    Heydarian, Neda; Favaedi, Raha; Sadighi Gilani, Mohammad Ali; Shahhoseini, Maryam

    2016-01-01

    Background: The availability of testis specific genes will be of help in choosing the most promising biomarkers for the detection of testicular sperm retrieval in patients with non-obstructive azoospermia (NOA). Testis specific chromodomain protein Y 1 (CDY1) is a histone acetyltransferase which concentrates in the round spermatid nucleus, where histone hyperacetylation occurs and causes the replacement of histones by the sperm-specific DNA packaging proteins, TNPs and PRMs. Objective: The aim was to evaluate CDY1 gene as a marker for predicting of successful sperm retrieval in NOA patients. Materials and Methods: This research was conducted on 29 patients with NOA who had undergone testicular sperm extraction (TESE) procedure. NOA patients were subdivided into patients with successful sperm retrieval (NOA+, n=12) and patients with unsuccessful sperm retrieval (NOA-, n=17). Relative expression of CDY1 gene and chromatin incorporation of CDY1 protein were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and ELISA assay, respectively. Results: Quantification of mRNA relative expression and incorporation of CDY1 protein in chromatin showed significant lower expressions and protein levels of CDY1 in testis tissues of NOA- in comparison to NOA+ group. Conclusion: The findings in this study demonstrated a correlation between the low levels of CDY1 function and unsuccessful sperm recovery in the testicular tissues of NOA- compared to NOA+ patients. Therefore, it can be reasonable to consider CDY1 as a potential biomarker for predicting the presence of spermatozoa, although the claim needs more samples to be confirmed. PMID:27525321

  5. Discovery of Potent and Orally Active p53-MDM2 Inhibitors RO5353 and RO2468 for Potential Clinical Development

    PubMed Central

    2013-01-01

    The development of small-molecule MDM2 inhibitors to restore dysfunctional p53 activities represents a novel approach for cancer treatment. In a previous communication, the efforts leading to the identification of a non-imidazoline MDM2 inhibitor, RG7388, was disclosed and revealed the desirable in vitro and in vivo pharmacological properties that this class of pyrrolidine-based inhibitors possesses. Given this richness and the critical need for a wide variety of chemical structures to ensure success in the clinic, research was expanded to evaluate additional derivatives. Here we report two new potent, selective, and orally active p53-MDM2 antagonists, RO5353 and RO2468, as follow-ups with promising potential for clinical development. PMID:24900784

  6. Discovery of Potent and Orally Active p53-MDM2 Inhibitors RO5353 and RO2468 for Potential Clinical Development.

    PubMed

    Zhang, Zhuming; Chu, Xin-Jie; Liu, Jin-Jun; Ding, Qingjie; Zhang, Jing; Bartkovitz, David; Jiang, Nan; Karnachi, Prabha; So, Sung-Sau; Tovar, Christian; Filipovic, Zoran M; Higgins, Brian; Glenn, Kelli; Packman, Kathryn; Vassilev, Lyubomir; Graves, Bradford

    2014-02-13

    The development of small-molecule MDM2 inhibitors to restore dysfunctional p53 activities represents a novel approach for cancer treatment. In a previous communication, the efforts leading to the identification of a non-imidazoline MDM2 inhibitor, RG7388, was disclosed and revealed the desirable in vitro and in vivo pharmacological properties that this class of pyrrolidine-based inhibitors possesses. Given this richness and the critical need for a wide variety of chemical structures to ensure success in the clinic, research was expanded to evaluate additional derivatives. Here we report two new potent, selective, and orally active p53-MDM2 antagonists, RO5353 and RO2468, as follow-ups with promising potential for clinical development. PMID:24900784

  7. A potentially artifact-free oral contrast agent for gastrointestinal MRI.

    PubMed

    Liebig, T; Stoupis, C; Ros, P R; Ballinger, J R; Briggs, R W

    1993-11-01

    The combination of diamagnetic barium sulfate and superparamagnetic iron oxide (SPIO) in one suspension produces a macroscopic cancellation of positive and negative magnetic susceptibility components that can potentially eliminate susceptibility artifacts even with gradient echo pulse sequences. The relaxation properties that make the SPIO suspension a useful negative contrast agent are retained. PMID:8259066

  8. Development of simple sequence repeat markers in persimmon (Diospyros L.) and their potential use in related species.

    PubMed

    Yang, Y; Jing, Z B; Ruan, X F; Cheng, J M

    2015-01-01

    Persimmon (Diospyros L.) is an economically important fruit in the world, and it has been recognized as a healthy nutrient supply for human consumption. In this study, 14 microsatellite markers were developed from an AG/TC and AC/TG-enriched genomic library of Chinese persimmon Mopanshi. Twelve polymorphic markers were selected in 4 related species; these markers showed transferability to the 4 related persimmon species. In addition, 10 simple sequence repeat (SSR) markers were used to detect the genetic diversity among 51 persimmon accessions from China, Japan, and Korea. A total of 57 polymorphic bands with an average of 5.7 bands per primer pair were observed. According to cluster analysis and principal coordinate analysis, all persimmon accessions could be divided into 4 groups. A close relationship existed between D. kaki and D. oleifera, and D. glaucifolia and D. lotus. Jinzaoshi could be considered a separate species of persimmon. These new SSR markers provide tools for evaluating genetic relatedness among different persimmon species. PMID:25729996

  9. β-lactoglobulin-pectin Nanoparticle-based Oral Drug Delivery System for Potential Treatment of Colon Cancer.

    PubMed

    Izadi, Zhila; Divsalar, Adeleh; Saboury, Ali Akbar; Sawyer, Lindsay

    2016-08-01

    Colon cancer is one of the most common internal malignancies, and conventional chemotherapy is not effective in its treatment. Nanoparticles hold tremendous potential as an effective drug delivery system. The physicochemical properties of β-lactoglobulin, the main whey protein of cow's milk, such as its stability at low pH, its resistance to gastric protease, and its ability to bind hydrophobic ligands, give it potential for transporting drugs specifically for colon cancer. In the present research, β-lactoglobulin-pectin nanoparticles were designed to transfer a newly synthesized, anticancer platinum complex (bipyridine ethyl dithiocarbamate Pt(II) nitrate), to the colon. The effects of multiple factors on the size and the colloidal stability of the nanoparticles were studied using dynamic light scattering and scanning electron microscopy techniques. Results showed that the best particle size and highest colloidal stability were obtained in phosphate buffer, pH 4.5, with 0.5 mg/mL β-lactoglobulin and 0.025-0.05wt% pectin. The drug release profile in simulated gastrointestinal conditions demonstrated that β-lactoglobulin with a secondary coating is stable in acidic conditions but is able to release its cargo at pH 7. Hence, these nanoparticles have potential to serve as novel and effective vehicles for oral drug delivery preparations. PMID:26896377

  10. MicroRNAs-208b-3p, 204-5p, 129-2-3p and 3065-5p as predictive markers of oral leukoplakia that progress to cancer.

    PubMed

    Philipone, Elizabeth; Yoon, Angela J; Wang, Shuang; Shen, Jing; Ko, Yen Chen Kevin; Sink, Jill M; Rockafellow, Andrew; Shammay, Nathanel A; Santella, Regina M

    2016-01-01

    Leukoplakia is the most common precursor lesion of oral squamous cell carcinoma (OSCC). Currently, the risk of progression to OSCC is assessed based on histopathologic examination alone. However, this method fails to identify the subset of microscopically innocuous leukoplakia that ultimately transforms to OSCC. The aim of this study was to determine if microRNAs (miRNAs) can be utilized to identify non- and low-grade dysplastic oral lesions at risk for cancer progression. A retrospective study of genome-wide miRNA expression level analyses was performed in the training cohort (n=20) using deep sequencing formalin-fixed paraffin embedded incisional biopsy tissues from patients with oral leukoplakic lesions diagnosed with non- or low-grade dysplasia and known clinical outcome. The promising miRNA candidates were then evaluated in the validation cohort (n=80) using quantitative real-time PCR (qRT-PCR). Four promising miRNAs-208b-3p, 204-5p, 129-2-3p and 3065-5p were identified. Combining these four miRNAs as a panel with age and histologic diagnosis (p<0.004), our final model had a predictive value for the area under the receiver operating characteristic (ROC) curve (AUC) of 0.792, sensitivity of 76.9% and specificity of 73.7% to accurately identify non- and low-grade dysplastic lesions at risk of cancer progression, which is a significant improvement over histopathologic examination alone (AUC of 0.645). While further investigation is needed, discovery of predictive markers that can accurately identify histologically innocuous oral lesions at high risk for progression to OSSC will significantly improve clinical outcome by means of early intervention. PMID:27508095

  11. MicroRNAs-208b-3p, 204-5p, 129-2-3p and 3065-5p as predictive markers of oral leukoplakia that progress to cancer

    PubMed Central

    Philipone, Elizabeth; Yoon, Angela J; Wang, Shuang; Shen, Jing; Ko, Yen Chen Kevin; Sink, Jill M; Rockafellow, Andrew; Shammay, Nathanel A; Santella, Regina M

    2016-01-01

    Leukoplakia is the most common precursor lesion of oral squamous cell carcinoma (OSCC). Currently, the risk of progression to OSCC is assessed based on histopathologic examination alone. However, this method fails to identify the subset of microscopically innocuous leukoplakia that ultimately transforms to OSCC. The aim of this study was to determine if microRNAs (miRNAs) can be utilized to identify non- and low-grade dysplastic oral lesions at risk for cancer progression. A retrospective study of genome-wide miRNA expression level analyses was performed in the training cohort (n=20) using deep sequencing formalin-fixed paraffin embedded incisional biopsy tissues from patients with oral leukoplakic lesions diagnosed with non- or low-grade dysplasia and known clinical outcome. The promising miRNA candidates were then evaluated in the validation cohort (n=80) using quantitative real-time PCR (qRT-PCR). Four promising miRNAs-208b-3p, 204-5p, 129-2-3p and 3065-5p were identified. Combining these four miRNAs as a panel with age and histologic diagnosis (p<0.004), our final model had a predictive value for the area under the receiver operating characteristic (ROC) curve (AUC) of 0.792, sensitivity of 76.9% and specificity of 73.7% to accurately identify non- and low-grade dysplastic lesions at risk of cancer progression, which is a significant improvement over histopathologic examination alone (AUC of 0.645). While further investigation is needed, discovery of predictive markers that can accurately identify histologically innocuous oral lesions at high risk for progression to OSSC will significantly improve clinical outcome by means of early intervention. PMID:27508095

  12. Potentiation of reactive oxygen species is a marker for synergistic cytotoxicity of MS-275 and 5-azacytidine in leukemic cells

    PubMed Central

    Gao, Shan; Mobley, Aaron; Miller, Claudia; Boklan, Jessica; Chandra, Joya

    2008-01-01

    Epigenetic modifiers are currently in clinical use for various tumor types. Recently, numerous studies supporting the combination of histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors have emerged, encouraging early clinical trials of these agents together. Here we show that MS-275, an HDACi, and 5-azacytidine, a methyltransferase inhibitor, display synergistic cytotoxicity and apoptosis in AML and ALL cells. Intracellular production of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, is a novel marker for this synergism in ALL cells. These data suggest that assessment of oxidative stress can serve as a marker of the concerted action of MS-275 and 5-azacytidine. PMID:18031811

  13. 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.

  14. Reducing the risk of xerostomia and mandibular osteoradionecrosis: the potential benefits of intensity modulated radiotherapy in advanced oral cavity carcinoma.

    PubMed

    Ahmed, Merina; Hansen, Vibeke N; Harrington, Kevin J; Nutting, Christopher M

    2009-01-01

    Radiation therapy for squamous cell carcinoma of the oral cavity may be curative, but carries a risk of permanent damage to bone, salivary glands, and other soft tissues. We studied the potential of intensity modulated radiotherapy (IMRT) to improve target volume coverage, and normal tissue sparing for advanced oral cavity carcinoma (OCC). Six patients with advanced OCC requiring bilateral irradiation to the oral cavity and neck were studied. Standard 3D conformal radiotherapy (3DCRT) and inverse-planned IMRT dose distributions were compared by using dose-volume histograms. Doses to organs at risk, including spinal cord, parotid glands, and mandible, were assessed as surrogates of radiation toxicity. PTV1 mean dose was 60.8 +/- 0.8 Gy for 3DCRT and 59.8 +/- 0.1 Gy for IMRT (p = 0.04). PTV1 dose range was 24.7 +/- 6 Gy for 3DCRT and 15.3 +/- 4 Gy for IMRT (p = 0.001). PTV2 mean dose was 54.5 +/- 0.8 Gy for 3DCRT and for IMRT was 54.2 +/- 0.2 Gy (p = 0.34). PTV2 dose range was improved by IMRT (7.8 +/- 3.2 Gy vs. 30.7 +/- 12.8 Gy, p = 0.006). Homogeneity index (HI) values for PTV2 were closer to unity using IMRT (p = 0.0003). Mean parotid doses were 25.6 +/- 2.7 Gy for IMRT and 42.0 +/- 8.8 Gy with 3DCRT (p = 0.002). The parotid V30 in all IMRT plans was <45%. The mandible V50, V55, and V60 were significantly lower for the IMRT plans. Maximum spinal cord and brain stem doses were similar for the 2 techniques. IMRT provided superior target volume dose homogeneity and sparing of organs at risk. The magnitude of reductions in dose to the salivary glands and mandible are likely to translate into reduced incidence of xerostomia and osteoradionecrosis for patients with OCC. PMID:19647632

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

    PubMed Central

    Cobb, CO; Weaver, MF; Eissenberg, T

    2011-01-01

    Background Non-combustible potential reduced exposure products (PREPs; eg, Star Scientific’s Ariva; a variety of other smokeless tobacco products) are marketed to reduce the harm associated with smoking. This marketing occurs despite an absence of objective data concerning the toxicant exposure and effects of these PREPs. Methods used to examine combustible PREPs were adapted to assess the acute effects of non-combustible PREPs for smokers. Methods 28 overnight abstinent cigarette smokers (17 men, 14 non-white) each completed seven, Latin-squared ordered, approximately 2.5 h laboratory sessions that differed by product administered: Ariva, Marlboro Snus (Philip Morris, USA), Camel Snus (RJ Reynolds, Winston-Salem, North Carolina, USA), Commit nicotine lozenge (GlaxoSmithKline; 2 mg), own brand cigarettes, Quest cigarettes (Vector Tobacco; delivers very low levels of nicotine) and sham smoking (ie, puffing on an unlit cigarette). In each session, the product was administered twice (separated by 60 min), and plasma nicotine levels, expired air CO and subjective effects were assessed regularly. Results Non-combustible products delivered less nicotine than own brand cigarettes, did not expose smokers to CO and failed to suppress tobacco abstinence symptoms as effectively as combustible products. Conclusions While decreased toxicant exposure is a potential indicator of harm reduction potential, a failure to suppress abstinence symptoms suggests that currently marketed non-combustible PREPs may not be a viable harm reduction strategy for US smokers. This study demonstrates how clinical laboratory methods can be used to evaluate the short-term effects of non-combustible PREPs for smokers. PMID:19346218

  16. Proteomic analysis allows for early detection of potential markers of metabolic impairment in very young obese children

    PubMed Central

    2014-01-01

    Apo A1 (IR vs. non-IR). Assays routinely used in the clinical setting (ELISA/kinetic nephelometry), only partially confirmed the changes observed by proteomic analysis (ApoA1 and haptoglobin). Conclusion Proteomic analysis can allow for the identification of potential new candidate biomarkers as a complement to routinely used assays to detect initial changes in serum markers of inflammation and lipid metabolism impairment in young obese children. PMID:24949022

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

    PubMed

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

    2011-08-01

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

  18. Short-term Effects of Air Temperature on Blood Markers of Coagulation and Inflammation in Potentially Susceptible Individuals

    EPA Science Inventory

    Objectives: Changes in air temperature are associated with an increase in cardiovascular events, but the role of pro-coagulant and pro-inflammatory blood markers is still poorly understood. We investigated the association between air temperature and fibrinogen, plasminogen act...

  19. Seven low-mass ions in pretreatment serum as potential predictive markers of the chemoradiotherapy response of rectal cancer.

    PubMed

    Roh, Kangsan; Yeo, Seung-Gu; Yoo, Byong Chul; Kim, Kyung-Hee; Kim, Sun Young; Kim, Min-Jeong

    2016-09-01

    Preoperative chemoradiotherapy (CRT) is generally performed for locally advanced rectal cancer (LARC, cStage 2 or 3) to improve local disease control and patient survival. The pathological tumor response to CRT is a surrogate marker that is associated with oncological outcome. Thus, markers that predict the response to CRT would be valuable for individualizing treatment for LARC patients. The current study used metabolomics-based approaches to identify molecular markers that predict the response to CRT. Seventy-six patients with LARC who received pelvic radiotherapy and concurrent chemotherapy using tegafur-uracil and leucovorin were enrolled. Radical surgery was performed 6-8 weeks after the completion of CRT. The postsurgical pathological CRT response was evaluated using the ypStage or tumor regression grade. Profiling patterns of low-mass ions (LMIs) in the pretreatment sera were obtained from all patients using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Our previously developed two-step algorithms, which showed a powerful diagnostic capability during colorectal cancer screening, were then used to screen for meaningful LMIs with discriminatory power. One combination consisting of seven LMIs was identified, whose discriminatory score separated a good CRT response (ypStage 0-1) from a poor CRT response (ypStage 3-4) successfully. However, each individual LMI alone showed insignificant discriminatory power. This finding suggests that analysis of the LMIs in pretreatment serum could serve as a predictive marker of the CRT response in patients with LARC. PMID:27272410

  20. 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

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

    PubMed Central

    Gebler-Hughes, Elizabeth S.; Kemp, Linda

    2014-01-01

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

  2. Deletion of macrophage migration inhibitory factor inhibits murine oral carcinogenesis: Potential role for chronic pro-inflammatory immune mediators.

    PubMed

    Oghumu, Steve; Knobloch, Thomas J; Terrazas, Cesar; Varikuti, Sanjay; Ahn-Jarvis, Jennifer; Bollinger, Claire E; Iwenofu, Hans; Weghorst, Christopher M; Satoskar, Abhay R

    2016-09-15

    Oral cancer kills about 1 person every hour each day in the United States and is the sixth most prevalent cancer worldwide. The pro-inflammatory cytokine 'macrophage migration inhibitory factor' (MIF) has been shown to be expressed in oral cancer patients, yet its precise role in oral carcinogenesis is not clear. In this study, we examined the impact of global Mif deletion on the cellular and molecular process occurring during oral carcinogenesis using a well-established mouse model of oral cancer with the carcinogen 4-nitroquinoline-1-oxide (4NQO). C57BL/6 Wild-type (WT) and Mif knock-out mice were administered with 4NQO in drinking water for 16 weeks, then regular drinking water for 8 weeks. Mif knock-out mice displayed fewer oral tumor incidence and multiplicity, accompanied by a significant reduction in the expression of pro-inflammatory cytokines Il-1β, Tnf-α, chemokines Cxcl1, Cxcl6 and Ccl3 and other molecular biomarkers of oral carcinogenesis Mmp1 and Ptgs2. Further, systemic accumulation of myeloid-derived tumor promoting immune cells was inhibited in Mif knock-out mice. Our results demonstrate that genetic Mif deletion reduces the incidence and severity of oral carcinogenesis, by inhibiting the expression of chronic pro-inflammatory immune mediators. Thus, targeting MIF is a promising strategy for the prevention or therapy of oral cancer. PMID:27164411

  3. Marker vaccine potential of a foot-and-mouth disease virus with a partial VP1 G-H loop deletion.

    PubMed

    Fowler, V L; Knowles, N J; Paton, D J; Barnett, P V

    2010-04-26

    Previous work in cattle and pigs demonstrated that protection against foot-and-mouth disease (FMD) could be achieved following vaccination with chimeric foot-and-mouth disease virus (FMDV) vaccines, in which the VP1 G-H loop had been substituted with that from another serotype. This indicated that the VP1 G-H loop may not be essential for the protection of natural hosts against FMDV. If this could be substantiated there would be potential to develop FMD marker vaccines, characterised by the absence of this region. Here, we investigate the serological responses to vaccination with a virus with a partial VP1 G-H loop deletion in order to determine the likelihood of achieving protection and the potential of this virus as a marker vaccine. Inactivated, oil adjuvanted, vaccines, consisting of chemically inactivated virus with or without a partially deleted VP1 G-H loop, were used to immunise cattle. Serum was collected on days 0, 7, 14 and 21 and antibody titres calculated using the virus neutralisation test (VNT) to estimate the likelihood of protection. We predict a good likelihood that cattle vaccinated with a vaccine characterised by a partial VP1 G-H loop would be protected against challenge with the same virus containing the VP1 G-H loop. We also present evidence on the potential of such a construct to act as a marker vaccine, when used in conjunction with a novel serological test. PMID:20199761

  4. The Potential for Glycemic Control Monitoring and Screening for Diabetes at Dental Visits Using Oral Blood

    PubMed Central

    Rosedale, Mary T.; Pesce, Michael A.; Rindskopf, David M.; Kaur, Navjot; Juterbock, Caroline M.; Wolff, Mark S.; Malaspina, Dolores; Danoff, Ann

    2015-01-01

    Objectives. We examined the potential for glycemic control monitoring and screening for diabetes in a dental setting among adults (n = 408) with or at risk for diabetes. Methods. In 2013 and 2014, we performed hemoglobin A1c (HbA1c) tests on dried blood samples of gingival crevicular blood and compared these with paired “gold-standard” HbA1c tests with dried finger-stick blood samples in New York City dental clinic patients. We examined differences in sociodemographics and diabetes-related risk and health care characteristics for 3 groups of at-risk patients. Results. About half of the study sample had elevated HbA1c values in the combined prediabetes and diabetes ranges, with approximately one fourth of those in the diabetes range. With a correlation of 0.991 between gingival crevicular and finger-stick blood HbA1c, measures of concurrence between the tests were extremely high for both elevated HbA1c and diabetes-range HbA1c levels. Persons already diagnosed with diabetes and undiagnosed persons aged 45 years or older could especially benefit from HbA1c testing at dental visits. Conclusions. Gingival crevicular blood collected at the dental visit can be used to screen for diabetes and monitor glycemic control for many at-risk patients. PMID:25713975

  5. 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.

  6. Subthalamic and Cortical Local Field Potentials Associated with Pilocarpine-Induced Oral Tremor in the Rat

    PubMed Central

    Long, Lauren L.; Podurgiel, Samantha J.; Haque, Aileen F.; Errante, Emily L.; Chrobak, James J.; Salamone, John D.

    2016-01-01

    Tremulous jaw movements (TJMs) are rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus. In rodents, TJMs are induced by neurochemical conditions that parallel those seen in human Parkinsonism, including neurotoxic or pharmacological depletion of striatal dopamine (DA), DA antagonism, and cholinomimetic administration. Moreover, TJMs in rodents can be attenuated by antiparkinsonian agents, including levodopa (L-DOPA), DA agonists, muscarinic antagonists, and adenosine A2A antagonists. In human Parkinsonian patients, exaggerated physiological synchrony is seen in the beta frequency band in various parts of the cortical/basal ganglia/thalamic circuitry, and activity in the tremor frequency range (3–7 Hz) also has been recorded. The present studies were undertaken to determine if tremor-related local field potential (LFP) activity could be recorded from motor cortex (M1) or subthalamic nucleus (STN) during the TJMs induced by the muscarinic agonist pilocarpine, which is a well-known tremorogenic agent. Pilocarpine induced a robust TJM response that was marked by rhythmic electromyographic (EMG) activity in the temporalis muscle. Compared to periods with no tremor activity, TJM epochs were characterized by increased LFP activity in the tremor frequency range in both neocortex and STN. Tremor activity was not associated with increased synchrony in the beta frequency band. These studies identified tremor-related LFP activity in parts of the cortical/basal ganglia circuitry that are involved in the pathophysiology of Parkinsonism. This research may ultimately lead to identification of the oscillatory neural mechanisms involved in the generation of tremulous activity, and promote development of novel treatments for tremor disorders. PMID:27378874

  7. Plasma levels of 25-hydroxyvitamin D3 and in vivo markers of cytochrome P450 3A activity in Swedes and Koreans: effects of a genetic polymorphism and oral contraceptives.

    PubMed

    Nylén, Hanna; Björkhem-Bergman, Linda; Ekström, Lena; Roh, Hyung-Keun; Bertilsson, Leif; Eliasson, Erik; Lindh, Jonatan D; Diczfalusy, Ulf

    2014-10-01

    In vitro studies have shown that vitamin D may induce several cytochrome P450 (CYP) enzymes in general and CYP3A4 in particular. The primary aim of this study was to investigate the relationship between plasma levels of 25-hydroxyvitamin D3 and suggested in vivo markers of CYP3A activity in healthy volunteers from Sweden and Korea. Plasma concentrations of 25-hydroxyvitamin D3 were analysed in samples from three previously performed studies, and the correlation between these levels and suggested in vivo markers of CYP3A activity was investigated by means of nonparametric correlation. In addition, we studied the modulating effects of three vitamin D receptor promoter polymorphisms on the association between 25-hydroxyvitamin D3 and CYP3A enzyme activity in Swedish subjects. The plasma levels of 25-hydroxyvitamin D3 were not significantly associated with CYP3A phenotypes in any of the three studies, but after accounting for the vitamin D receptor polymorphism rs4516035, there was a significant positive association between 25-hydroxyvitamin D3 and CYP3A activity (p = 0.004). Swedes (n = 65) had significantly higher 25-hydroxyvitamin D3 levels than Koreans (n = 67), 75 nM compared with 31 nM (p < 0.001). Swedish women taking oral contraceptives (OC) (n = 19) had somewhat higher plasma levels of 25-hydroxyvitamin D3 compared with Swedish women not taking oral contraceptives (n = 21), 89 and 72 nM, respectively (p = 0.02). In conclusion, our results suggest that the overall influence on the CYP3A activity by 25-hydroxyvitamin D3 is of marginal importance. PMID:24655660

  8. Dental neglect as a marker of broader neglect: a qualitative investigation of public health nurses’ assessments of oral health in preschool children

    PubMed Central

    2013-01-01

    Background Child neglect is a pernicious child protection issue with adverse consequences that extend to adulthood. Simultaneously, though it remains prevalent, childhood dental caries is a preventable disease. Public health nurses play a pivotal role in assessing oral health in children as part of general health surveillance. However, little is known about how they assess dental neglect or what their thresholds are for initiating targeted support or instigating child protection measures. Understanding these factors is important to allow improvements to be made in care pathways. Methods We investigated public health nurses’ assessment of oral health in preschool children in relation to dental neglect and any associations they make with child neglect more broadly. A qualitative study was conducted in Scotland during 2011/12. Sixteen public health nurses were recruited purposively from one health region. Individual, semi-structured interviews were undertaken and data were analyzed inductively using a framework approach. Categories were subsequently mapped to the research questions. Results Public health nurses assess oral health through proxy measures, opportunistic observation and through discussion with parents. Dental neglect is rarely an isolated issue that leads on its own to child protection referral. It tends to be other presenting issues that initiate a response. Threshold levels for targeted support were based on two broad indicators: social issues and concerns about child (and parental) dental health. Thresholds for child protection intervention were untreated dental caries or significant dental pain. Barriers to intervention are that dental neglect may be ‘unseen’ and ‘unspoken’. The study revealed a communication gap in the care pathway for children where a significant dental problem is identified. Conclusions Public health nurses take their child protection role seriously, but rarely make a link between dental caries and child neglect. Clear

  9. Comparative Correlation Structure of Colon Cancer Locus Specific Methylation: Characterisation of Patient Profiles and Potential Markers across 3 Array-Based Datasets

    PubMed Central

    Barat, Ana; Ruskin, Heather J.

    2015-01-01

    Abnormal DNA-methylation is well known to play an important role in cancer onset and development, and colon cancer is no exception to this rule. Recent years have seen the increased use of large-scale technologies, (such as methylation microarray assays or specific sequencing of methylated DNA), to determine whole genome profiles of CpG island methylation in tissue samples. Comprehensive study of methylation array data from transcriptome high-throughput platforms permits determination of gene methylation markers, important for cancer profiling. Here, three large-scale methylation datasets for colon cancer have been compared to determine locus-specific methylation agreement. These data are from the GEO database, where colon cancer and apparently healthy adjacent tissues are represented by sample sizes 125 and 29 respectively in the first dataset, 24 of each in the second and 118 of each in the third. Several data analysis techniques have been employed, including Clustering, Discriminant Principal Component Analysis, Discriminant Analysis and ROC curves, in order (i) to obtain a better insight on the locus-specific concomitant methylation structures for these diverse data and (ii) to determine a robust potential marker set for indicative screening, drawn from all data taken together. The extent of the agreement between the analysed datasets is reported. Further, potential screening methylation markers, for which methylation profiles are consistent across tissue samples and several datasets, are highlighted and discussed. PMID:26185542

  10. C-deletion in exon 4 codon 63 of p53 gene as a molecular marker for oral squamous cell carcinoma: A preliminary study

    PubMed Central

    Sukhija, Hemani; Krishnan, Rajkumar; Balachander, N.; Raghavendhar, Karthik; Ramadoss, Ramya; Sen, Sukanta

    2015-01-01

    Background: Exfoliated oral cancer cells in saliva samples from patients with oral squamous cell carcinoma (OSCC) can be used to determine the incidence and type of mutations of the p53 tumor suppressor gene. The purpose of this study was to identify C-deletion mutation in exon 4 codon 63 of p53 gene in the saliva of OSCC patients by polymerase chain reaction (PCR). Materials and Methods: Saliva samples of 20 newly histopathologically diagnosed OSCC patients and 5 healthy volunteers were subjected to isolation of the total genomic DNA and PCR amplification for C-deletion on exon 4 of p53 gene. The resulting products were resolved by agarose gel electrophoresis, viewed and photographed on ultraviolet-transilluminator. Results: The relationship between the frequencies of genetic alterations was assessed by Chi-square test. Differences with values of P < 0.05 were statistically significant. Conclusion: The study concluded a 100% presence of C-deletion mutation in exon 4 codon 63 of p53 in the saliva of OSCC patients. This study suggests that detection of mutation in exon 4 codon 63 of p53 by PCR is a fast, reliable, accurate, and sensitive molecular method for OSCC diagnosis. PMID:26604578

  11. Marker development

    SciTech Connect

    Adams, M.R.

    1987-05-01

    This report is to discuss the marker development for radioactive waste disposal sites. The markers must be designed to last 10,000 years, and place no undue burdens on the future generations. Barriers cannot be constructed that preclude human intrusion. Design specifications for surface markers will be discussed, also marker pictograms will also be covered.

  12. Evaluating the potential impact of a mobile telemedicine system on coordination of specialty care for patients with complicated oral lesions in Botswana.

    PubMed

    Tesfalul, Martha; Littman-Quinn, Ryan; Antwi, Cynthia; Ndlovu, Siphiwo; Motsepe, Didintle; Phuthego, Motsholathebe; Tau, Boitumelo; Mohutsiwa-Dibe, Neo; Kovarik, Carrie

    2016-04-01

    Mobile telemedicine involves the use of mobile device (e.g., cell phones, tablets) technology to exchange information to assist in the provision of patient care. Throughout the world, mobile telemedicine initiatives are increasing in number and in scale, but literature on their impact on patient outcomes in low-resource areas is limited. This study explores the potential impact of a mobile oral telemedicine system on the oral health specialty referral system in Botswana. Analysis of 26 eligible cases from June 2012 to July 2013 reveals high diagnosis concordance between dental officers and oral health specialists at 91.3% (21/23) but significant management plan discordance at 64.0% (16/25), over two-thirds of which involved the specialists disagreeing with the referring clinicians about the need for a visit to a specialist. These findings suggest mobile telemedicine can optimize the use of insights and skills of specialists remotely in regions where they are scarce. PMID:26510877

  13. 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

  14. [Oral viral infections].

    PubMed

    Parent, Dominique

    2016-02-01

    Exclude herpes infection in the presence of acute oral ulcers of unknown origin, particularly in patients in poor general condition. Remember that asymptomatic HSV-1 shedding in saliva may result in an oral-genital transmission. Perform an anogenital examination and a screening for other sexually transmitted diseases when oral warts are diagnosed. Search for immunosuppression and monitor the patient (screening for a potential associated carcinoma) when there is rapid growth of oral warts. Consider all the clinical signs (systemic, skin, other mucosa, immunity...) when a patient has an enanthem or oral ulcerations. Ask for a HIV test when an oral Kaposi's sarcoma, a hairy leukoplakia or major aphthae are diagnosed. PMID:26854091

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

    PubMed

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

    2010-04-01

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

  16. 1’-Acetoxychavicol acetate inhibits growth of human oral carcinoma xenograft in mice and potentiates cisplatin effect via proinflammatory microenvironment alterations

    PubMed Central

    2012-01-01

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

  17. The Potential Utility of Blood-Derived Biochemical Markers as Indicators of Early Clinical Trends Following Severe Traumatic Brain Injury

    PubMed Central

    DeFazio, Michael; Rammo, Richard; Robles, Jaime R.; Bramlett, Helen M.; Dietrich, W. Dalton; Bullock, M. Ross

    2016-01-01

    OBJECTIVE Severe traumatic brain injury (TBI) is a dynamic neuropathologic process in which a substantial proportion of patients die within the first 48-hours. The assessment of injury severity and prognosis are of primary concern in the initial management of severe TBI. Supplemental testing that aids in the stratification of patients at high risk for deterioration may significantly improve posttraumatic management in the acute setting. METHODS This retrospective study assessed the utility of both single-marker and multimarker models as predictive indicators of acute clinical status after severe TBI. Forty-four patients who sustained severe TBI (admission Glasgow Coma Scale [GCS] score ≤8) were divided into two cohorts according to a dichotomized clinical outcome at 72 hours after admission: Poor status (death or GCS score ≤8) and improved status (GCS score improved to >8). Threshold values for clinical status prediction were calculated for serum S-100B, matrix metalloproteinase-9, and plasma D-dimer, upon admission and at 24 hours after TBI by the use of receiver operating characteristic analysis. Performance characteristics of these single-marker predictors were compared with those derived from a multimarker logistic regression analysis. RESULTS Biomarkers with the greatest predictive value for poor status at 72 hours included serum S-100B on admission, as well as plasma D-dimer and serum S-100B at 24 hours, for which, associations were strongly significant. Multimarker analysis indicated no substantial improvement in prediction accuracy over the best single predictors during this time frame. CONCLUSION In conjunction with other clinical, physical, and radiologic evidence, blood-derived biochemical markers may serve to enhance prediction of early clinical trends after severe TBI. PMID:23313262

  18. Claudin-3 expression in radiation-exposed rat models: A potential marker for radiation-induced intestinal barrier failure

    SciTech Connect

    Shim, Sehwan; Lee, Jong-geol; Bae, Chang-hwan; Lee, Seung Bum; Jang, Won-Suk; Lee, Sun-Joo; Lee, Seung-Sook; Park, Sunhoo

    2015-01-02

    Highlights: • Irradiation increased intestinal bacterial translocation, accompanied by claudin protein expression in rats. • Neurotensin decreased the bacterial translocation and restored claudin-3 expression. • Claudin-3 can be used as a marker in evaluating radiation induced intestinal injury. - Abstract: The molecular events leading to radiation-induced intestinal barrier failure are not well known. The influence of the expression of claudin proteins in the presence and absence of neurotensin was investigated in radiation-exposed rat intestinal epithelium. Wistar rats were randomly divided into control, irradiation, and irradiation + neurotensin groups, and bacterial translocation to the mesenteric lymph node and expression of claudins were determined. Irradiation led to intestinal barrier failure as demonstrated by significant bacterial translocation. In irradiated terminal ilea, expression of claudin-3 and claudin-4 was significantly decreased, and claudin-2 expression was increased. Administration of neurotensin significantly reduced bacterial translocation and restored the structure of the villi as seen by histologic examination. Among the three subtype of claudins, only claudin-3 expression was restored. These results suggest that the therapeutic effect of neurotensin on the disruption of the intestinal barrier is associated with claudin-3 alteration and that claudin-3 could be used as a marker in evaluating radiation-induced intestinal injury.

  19. Potential of Start Codon Targeted (SCoT) markers to estimate genetic diversity and relationships among Chinese Elymus sibiricus accessions.

    PubMed

    Zhang, Junchao; Xie, Wengang; Wang, Yanrong; Zhao, Xuhong

    2015-01-01

    Elymus sibiricus as an important forage grass and gene pool for improving cereal crops, that is widely distributed in West and North China. Information on its genetic diversity and relationships is limited but necessary for germplasm collection, conservation and future breeding. Start Codon Targeted (SCoT) markers were used for studying the genetic diversity and relationships among 53 E. sibiricus accessions from its primary distribution area in China. A total of 173 bands were generated from 16 SCoT primers, 159 bands of which were polymorphic with the percentage of polymorphic bands (PPB) of 91.91%. Based upon population structure analysis five groups were formed. The cluster analysis separated the accessions into two major clusters and three sub-clusters, similar to results of principal coordinate analysis (PCoA). The molecular variance analysis (AMOVA) showed that genetic variation was greater within geographical regions (50.99%) than between them (49.01%). Furthermore, the study also suggested that collecting and evaluating E. sibiricus germplasm for major geographic regions and special environments broadens the available genetic base and illustrates the range of variation. The results of the present study showed that SCoT markers were efficient in assessing the genetic diversity among E. sibiricus accessions. PMID:25853316

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

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

  1. 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

  2. Genetic expression of adipose derived stem cell and smooth muscle cell markers to monitor differentiation potential following low intensity laser irradiation

    NASA Astrophysics Data System (ADS)

    Abrahamse, Heidi

    2014-02-01

    Mesenchymal stem cells (MSCs) have the capacity to differentiate into a variety of cell types that could potentially be used in tissue engineering and regenerative medicine. Low intensity laser irradiation (LILI) has been shown to induce a significant increase in cell viability and proliferation. Growth factors such as retinoic acid (RA) and transforming growth factor β1 (TGF-β1) play important roles in the differentiation of cells. The aim of this study was to investigate whether LILI in combination with growth factors could induce the differentiation of adipose derived stem cells (ADSCs) cocultured with smooth muscle cells (SMCs). The study used primary and continuous ADSC cell lines and a SMC line (SKUT-1) as control. Cells were co-cultured directly at a ratio of 1:1 using established methods, with and without growth factors and then exposed to LILI at 5 J/cm2 using a 636 nm diode laser. The cellular morphology, viability and proliferation of the co-cultures were assessed over a period of one week. The study also monitored the expression of cell specific markers over the same period of time. Genetic expression of the markers for both adipose derived stem cells (β1 Integrin and Thymidine 1) and smooth muscle cells (Heavy Myosin Chain) was monitored using flow cytometry. Cell viability and proliferation increased significantly in the co-cultured groups that were exposed to laser alone, as well as in combination with growth factors. Furthermore, there was a significant decrease in the expression of stem cell markers in the ADSCs over time. The results indicate that LILI in combination with growth factors not only increases the viability and proliferation of co-cultured cells but also decreases the expression of ADSC stem cell markers. This could indicate the possible differentiation of ADSCs into SMCs.

  3. Hypocortisolism as a potential marker of allostatic load in children: Associations with family risk and internalizing disorders

    PubMed Central

    Watamura, Sarah Enos; Hankin, Benjamin L.

    2014-01-01

    Although the majority of research attention to the HPA-axis in stress-related disorders and as a marker of allostatic load has focused on over-activation of this stress system, theory and data clearly indicate that under-activation is also an important type of dysregulation. In the current study, we focused on low cortisol, exploring a constellation of risk factors comprised of stress exposure, maternal depression, and attenuated basal and stress reactive cortisol in two samples of children. The first sample is 110 preschoolers living in high stress environments. Cortisol was assessed across the day at home and at child care as well as across two stress paradigms. These data were used to classify whether children’s HPA-axis activity was attenuated. Serious family financial strain, maternal depression, and attenuated cortisol all made unique contributions in models predicting current clinical levels of internalizing symptoms as rated by mothers and teachers. The second sample was 166 3rd, 6th, and 9th graders studied 5 times across a 1-year period. Maternal and child depression were determined through structured clinical interviews, and stress exposure was assessed via checklist and interview techniques with the child and the parent. Cortisol was assessed multiple times across a lab visit at time 1, and these data were combined into a single continuous measure. Cortisol concentrations across the lab visit interacted with stress exposure across the year such that children with lower average cortisol at time 1, maternal depressive symptoms, and increased stress across the 12 months showed increasing levels of internalizing symptoms. Based on these and related data we propose that prior to puberty, low cortisol may be an important marker of allostatic load, particularly for risk of depression and anxiety. PMID:21756439

  4. Bone Markers

    MedlinePlus

    ... Alkaline Phosphatase; Osteocalcin; P1NP; Procollagen Type 1 N-Terminal Propeptide Formal name: Biochemical Markers of Bone Remodeling ... tests for evaluating bone turnover: C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a marker ...

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

    PubMed

    Ahmadi, Amirhossein

    2012-08-01

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

  6. Mutation at embB codon 306, a potential marker for the identification of multidrug resistance associated with ethambutol in Mycobacterium tuberculosis.

    PubMed

    Cuevas-Córdoba, Betzaida; Juárez-Eusebio, Dulce María; Almaraz-Velasco, Raquel; Muñiz-Salazar, Raquel; Laniado-Laborin, Rafael; Zenteno-Cuevas, Roberto

    2015-09-01

    Ethambutol inhibits arabinogalactan and lipoarabinomannan biosynthesis in mycobacteria. The occurrence of mutations in embB codon 306 in ethambutol-susceptible isolates and their absence in resistant isolates has raised questions regarding the utility of this codon as a potential marker for resistance against ethambutol. The characterization of mutations on embB 306 will contribute to a better understanding of the mechanisms of resistance to this drug; therefore, the purpose of this study was to investigate the association between embB 306 mutations and first-line drug resistance profiles in tuberculosis isolates. We sequenced the region surrounding the embB 306 codon in 175 tuberculosis clinical isolates, divided according to drug sensitivity, in three groups: 110 were resistant to at least one first-line drug, of which 61 were resistant to ethambutol (EMB(r)), 49 were sensitive to ethambutol (EMB(s)) but were resistant to another drug, and 65 were pansensitive isolates (P(s)). The associations between embB 306 mutations and phenotypic resistance to all first-line drugs were determined, and their validity and safety as a diagnostic marker were assessed. One of the P(s) isolates (1/65), one of the EMB(s) isolates (1/49), and 20 of the EMB(r) isolates (20/61) presented with an embB 306 mutation. Four different single-nucleotide polymorphisms (SNPs) at embB 306 were associated with simultaneous resistance to ethambutol, isoniazid, and rifampin (odds ratio [OR], 17.7; confidence interval [CI], 5.6 to 56.1) and showed a positive predictive value of 82%, with a specificity of 97% for diagnosing multidrug resistance associated with ethambutol, indicating its potential as a molecular marker for several drugs. PMID:26124153

  7. Mutation at embB Codon 306, a Potential Marker for the Identification of Multidrug Resistance Associated with Ethambutol in Mycobacterium tuberculosis

    PubMed Central

    Cuevas-Córdoba, Betzaida; Juárez-Eusebio, Dulce María; Almaraz-Velasco, Raquel; Muñiz-Salazar, Raquel; Laniado-Laborin, Rafael

    2015-01-01

    Ethambutol inhibits arabinogalactan and lipoarabinomannan biosynthesis in mycobacteria. The occurrence of mutations in embB codon 306 in ethambutol-susceptible isolates and their absence in resistant isolates has raised questions regarding the utility of this codon as a potential marker for resistance against ethambutol. The characterization of mutations on embB 306 will contribute to a better understanding of the mechanisms of resistance to this drug; therefore, the purpose of this study was to investigate the association between embB 306 mutations and first-line drug resistance profiles in tuberculosis isolates. We sequenced the region surrounding the embB 306 codon in 175 tuberculosis clinical isolates, divided according to drug sensitivity, in three groups: 110 were resistant to at least one first-line drug, of which 61 were resistant to ethambutol (EMBr), 49 were sensitive to ethambutol (EMBs) but were resistant to another drug, and 65 were pansensitive isolates (Ps). The associations between embB 306 mutations and phenotypic resistance to all first-line drugs were determined, and their validity and safety as a diagnostic marker were assessed. One of the Ps isolates (1/65), one of the EMBs isolates (1/49), and 20 of the EMBr isolates (20/61) presented with an embB 306 mutation. Four different single-nucleotide polymorphisms (SNPs) at embB 306 were associated with simultaneous resistance to ethambutol, isoniazid, and rifampin (odds ratio [OR], 17.7; confidence interval [CI], 5.6 to 56.1) and showed a positive predictive value of 82%, with a specificity of 97% for diagnosing multidrug resistance associated with ethambutol, indicating its potential as a molecular marker for several drugs. PMID:26124153

  8. Oral hygiene status in a general population of Iran, 2011: a key lifestyle marker in relation to common risk factors of non-communicable diseases

    PubMed Central

    Asgari, Fereshteh; Majidi, Azam; Koohpayehzadeh, Jalil; Etemad, Koorosh; Rafei, Ali

    2015-01-01

    Background: To estimate Oral Hygiene (OH) status in the Iranian population in 2011, and to determine the influence of socio-economic characteristics on OH, and its interrelation with common risk factors of Non-Communicable Diseases (NCDs). Methods: Data including a total of 12,105 individuals aged 6-70 years were obtained from the sixth round of the surveys of NCDs risk factors in Iran. OH was recorded through a structured questionnaire measuring daily frequencies of tooth brushing and dental flossing. Descriptive analyses were performed on demographic characteristics in the complex sample survey setting. We also employed weighted binary logistic regression to compute Odds Ratio (OR) as a measure of association between the response and explanatory factors. Furthermore, to construct an asset index, we utilized Principal Component Analysis (PCA). Results: The percentage with minimum recommended daily OH practices was 3.7% among men and 7.7% among women (OR= 2.3; P< 0.001). Urban citizens were more likely to have their teeth cleaned compared to rural people (OR= 2.8; P< 0.001). For both genders, a relatively better condition was observed in the 25–34 age group (male: 5.6%; female: 10.3%). In addition, OH status improved significantly by increase in both level of education (P< 0.001) and economic status (P< 0.001). There were also apparent associations between self-care practices and specific behavioral risk factors, though the correlation with dietary habits and tobacco use could be largely explained by socio-economic factors. Conclusion: OH situation in Iran calls for urgent need to assign proper interventions and strategies toward raising public awareness and reducing disparities in access to health facilities. PMID:26029893

  9. Early Stage Diagnosis of Oral Cancer Using 1H NMR-Based Metabolomics12

    PubMed Central

    Tiziani, Stefano; Lopes, Victor; Günther, Ulrich L

    2009-01-01

    Oral cancer is the eighth most common cancer worldwide and represents a significant disease burden. If detected at an early stage, survival from oral cancer is better than 90% at 5 years, whereas late stage disease survival is only 30%. Therefore, there is an obvious clinical utility for novel metabolic markers that help to diagnose oral cancer at an early stage and to monitor treatment response. In the current study, blood samples of oral cancer patients were analyzed using nuclear magnetic resonance spectroscopy to derive a metabolic signature for oral cancer. Using multivariate chemometric analysis, we obtained an excellent discrimination between serum samples from cancer patients and from a control group and could also discriminate between different stages of disease. The metabolic profile obtained for oral cancer is significant, even for early stage disease and relatively small tumors. This suggests a systemic metabolic response to cancer, which bears great potential for early diagnosis. PMID:19242608

  10. Prolactin-induced protein as a potential therapy response marker of adjuvant chemotherapy in breast cancer patients

    PubMed Central

    Jablonska, Karolina; Grzegrzolka, Jedrzej; Podhorska-Okolow, Marzenna; Stasiolek, Mariusz; Pula, Bartosz; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Piotrowska, Aleksandra; Rys, Janusz; Ambicka, Aleksandra; Ong, Siew Hwa; Zabel, Maciej; Dziegiel, Piotr

    2016-01-01

    Many studies are dedicated to exploring the molecular mechanisms of chemotherapy-resistance in breast cancer (BC). Some of them are focused on searching for candidate genes responsible for this process. The aim of this study was typing the candidate genes associated with the response to standard chemotherapy in the case of invasive ductal carcinoma. Frozen material from 28 biopsies obtained from IDC patients with different responses to chemotherapy were examined using gene expression microarray, Real-Time PCR (RT-PCR) and Western blot (WB). Based on the microarray results, further analysis of candidate gene expression was evaluated in 120 IDC cases by RT-PCR and in 224 IDC cases by immunohistochemistry (IHC). The results were correlated with clinical outcome and molecular subtype of the BC. Gene expression microarray revealed Prolactin-Induced Peptide (PIP) as a single gene differentially expressed in BC therapy responder or non-responder patients (p <0.05). The level of PIP expression was significantly higher in the BC therapy responder group than in the non-responder group at mRNA (p=0.0092) and protein level (p=0.0256). Expression of PIP mRNA was the highest in estrogen receptor positive (ER+) BC cases (p=0.0254) and it was the lowest in triple negative breast cancer (TNBC) (p=0.0336). Higher PIP mRNA expression was characterized by significantly longer disease free survival (DFS, p=0.0093), as well as metastasis free survival (MFS, p=0.0144). Additionally, PIP mRNA and PIP protein expression levels were significantly higher in luminal A than in other molecular subtypes and TNBC. Moreover significantly higher PIP expression was observed in G1, G2 vs. G3 cases (p=0.0027 and p=0.0013, respectively). Microarray analysis characterized PIP gene as a candidate for BC standard chemotherapy response marker. Analysis of clinical data suggests that PIP may be a good prognostic and predictive marker in IDC patients. Higher levels of PIP were related to longer DFS and MFS

  11. 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(ε-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

  12. DNA marker-assisted evaluation of potato genotypes for potential resistance to potato cyst nematode pathotypes not yet invading into Japan.

    PubMed

    Asano, Kenji; Kobayashi, Akira; Tsuda, Shogo; Nishinaka, Mio; Tamiya, Seiji

    2012-06-01

    One of major objectives of crop breeding is conferring resistance to diseases and pests. However, large-scale phenotypic evaluation for many diseases and pests is difficult because strict controls are required to prevent their spread. Detection of disease resistance genes by using DNA markers may be an alternative approach to select potentially resistant accessions. Potato (Solanum tuberosum L.) breeders in Japan extensively use resistance gene H1, which confers nearly absolute resistance to potato cyst nematode (Globodera rostochiensis) pathotype Ro1, the only pathotype found in Japan. However, considering the possibility of accidental introduction of the other pathotypes, breeding of resistant varieties is an important strategy to prevent infestation by non-invading pathotypes in Japan. In this study, to evaluate the prevalence of resistance genes in Japanese genetic resources, we developed a multiplex PCR method that simultaneously detects 3 resistance genes, H1, Gpa2 and Gro1-4. We revealed that many Japanese varieties possess not only H1 but Gpa2, which are potentially resistant to other pathotypes of potato cyst nematode. On the other hand, no genotype was found to have the Gro1-4, indicating importance of introduction of varieties having Gro1-4. Our results demonstrate the applicability of DNA-marker assisted evaluation of resistant potato genotypes without phenotypic evaluation. PMID:23136525

  13. The first mitochondrial genome of Coelomactra antiquata (Mollusca: Veneroida: Mactridae) from Guangxi (China) and potential molecular markers.

    PubMed

    Shen, Xin; Meng, Xueping; Tian, Mei; Yan, Binlun; Cheng, Hanliang; Lu, Wei; Chai, Yuling

    2016-09-01

    The complete mitochondrial genome of Coelomactra antiquata (Guangxi, in China, GX) was determined. It is 16 801 bp in length and is the first representative from this province. The mitochondrial genome encodes 35 genes, including 12 PCGs, two ribosomal RNA, and 21 transfer RNA genes. Atp8 and trnSer(UCN) genes are missing, compared with the typical gene content of animal mitochondrial genomes. Three (cob, nad1, nad4, and nad6) of the 12 PCGs in the mitochondrial genome initiate with the ATA, while other PCGs start with ATG. Two PCGs (atp6 and nad4L) end with incomplete stop codons (T-), and the remaining ones have complete stop codons (TAA or TAG). The largest non-coding region of the C. antiquata (GX) contains one section of tandem repeats (5 × 99 bp). Among all PCGs and rRNAs, the nad5 gene contains the maximum polymorphic sites (430), followed by nad4 (261) and cox2 (240). Two ribosomal RNA genes (srRNA and lrRNA) and cox1 are most conservative. The proportions of polymorphic sites in six genes (nad4, nad2, nad6, nad5, cox2, and nad3) are more than 20% (ranging from 20.25% to 25.21%). These high variable genes can be used as molecular markers in the population genetic analysis of the species. PMID:26329456

  14. 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

  15. Early G1 cyclin-dependent kinases as prognostic markers and potential therapeutic targets in esophageal adenocarcinoma

    PubMed Central

    Ismail, Amin; Bandla, Santhoshi; Reveiller, Marie; Toia, Liana; Zhou, Zhongren; Gooding, William E.; Kalatskaya, Irina; Stein, Lincoln; D’Souza, Mary; Litle, Virginia R.; Peters, Jeffrey H.; Pennathur, Arjun; Luketich, James D.; Godfrey, Tony E.

    2011-01-01

    Purpose Chromosomal gain at 7q21 is a frequent event in esophageal adenocarcinoma (EAC). However, this event has not been mapped with fine resolution in a large EAC cohort and its association with clinical endpoints and functional relevance are unclear. Experimental design We used a cohort of 116 patients to fine map the 7q21 amplification using SNP microarrays. Prognostic significance and functional role of 7q21 amplification and its gene expression were explored. Results Amplification of the 7q21 region was observed in 35% of tumors with a focal, minimal amplicon containing 6 genes. 7q21 amplification was associated with poor survival and analysis of gene expression identified CDK6 as the only gene in the minimal amplicon whose expression was also associated with poor survival. A low level amplification (10%) was observed at the 12q13 region containing the CDK6 homolog, CDK4. Both amplification and expression of CDK4 correlated with poor survival. A combined model of both CDK6 and CDK4 expression is a superior predictor of survival than either alone. Specific knockdown of CDK4 and/or CDK6 by siRNAs shows that they are required for proliferation of EAC cells and that their function is additive. PD-0332991 targets the kinase activity of both molecules and suppresses proliferation and anchorage-independence of EAC cells through activation of the pRB pathway. Conclusions We suggest that CDK6 is the driver of 7q21 amplification and that both CDK4 and CDK6 are prognostic markers and bona fide oncogenes in EAC. Targeting these molecules may constitute a viable new therapy for this disease. PMID:21593195

  16. Survey and analysis of microsatellites from transcript sequences in Phytophthora species: frequency, distribution, and potential as markers for the genus

    PubMed Central

    Garnica, Diana P; Pinzón, Andrés M; Quesada-Ocampo, Lina M; Bernal, Adriana J; Barreto, Emiliano; Grünwald, Niklaus J; Restrepo, Silvia

    2006-01-01

    Background Members of the genus Phytophthora are notorious pathogens with world-wide distribution. The most devastating species include P. infestans, P. ramorum and P. sojae. In order to develop molecular methods for routinely characterizing their populations and to gain a better insight into the organization and evolution of their genomes, we used an in silico approach to survey and compare simple sequence repeats (SSRs) in transcript sequences from these three species. We compared the occurrence, relative abundance, relative density and cross-species transferability of the SSRs in these oomycetes. Results The number of SSRs in oomycetes transcribed sequences is low and long SSRs are rare. The in silico transferability of SSRs among the Phytophthora species was analyzed for all sets generated, and primers were selected on the basis of similarity as possible candidates for transferability to other Phytophthora species. Sequences encoding putative pathogenicity factors from all three Phytophthora species were also surveyed for presence of SSRs. However, no correlation between gene function and SSR abundance was observed. The SSR survey results, and the primer pairs designed for all SSRs from the three species, were deposited in a public database. Conclusion In all cases the most common SSRs were trinucleotide repeat units with low repeat numbers. A proportion (7.5%) of primers could be transferred with 90% similarity between at least two species of Phytophthora. This information represents a valuable source of molecular markers for use in population genetics, genetic mapping and strain fingerprinting studies of oomycetes, and illustrates how genomic databases can be exploited to generate data-mining filters for SSRs before experimental validation. PMID:17007642

  17. BC200 LncRNA a potential predictive marker of poor prognosis in esophageal squamous cell carcinoma patients

    PubMed Central

    Zhao, Rui-Hua; Zhu, Cai-hua; Li, Xiang-Ke; Cao, Wei; Zong, Hong; Cao, Xin-Guang; Hu, Hai-Yan

    2016-01-01

    Objective To explore the expression and prognosis significance of BC200 in esophageal squamous cell carcinoma (ESCC) patients who received radical resection. Methods We used quantitative real-time polymerase chain reaction to detect the expression level of BC200 in cancer tissue and paired adjacent normal tissue samples from 70 ESCC patients who received radical surgical resection and analyzed the correlation of the relative expression level of BC200 with clinical-pathological features and prognosis. Results We found that the relative expression of BC200 was significantly higher in ESCC tissues compared with adjacent normal tissue samples (P=0.023). But the expression of BC200 were not related to clinical-pathological features, such as age, TNM stages, and histological grade (P>0.05). Kaplan–Meier analysis showed that high expression levels of BC200 were correlated with poor prognosis in ESCC patients. Patients with a high level of BC200 had a shorter disease-free survival and overall survival than those with low BC200 expression (P=0.034 and P=0.031, respectively). On multivariate analysis, the hazard ratio (HR) of BC200 expression was 2.17 (95% confidence interval [CI]=1.12–4.19, P=0.022) for disease-free survival and 2.24 (95% CI=1.12–4.49, P=0.023) for overall survival. Conclusion Our results indicate that high expression of BC200 reflects poor prognosis and could serve as a novel predictive marker for ESCC patients who received radical resection. PMID:27143917

  18. Collection of exhaled breath condensate and analysis of hydrogen peroxide as a potential marker of lower airway inflammation in cats.

    PubMed

    Kirschvink, Nathalie; Marlin, David; Delvaux, François; Leemans, Jérôme; Clercx, Cécile; Sparkes, Andrew; Gustin, Pascal

    2005-05-01

    The objective of this study was to describe a standardised and non-invasive method for exhaled breath condensate (EBC) collection in cats and to test whether determination of hydrogen peroxide (H(2)O(2)) in EBC might be used as marker of lower airway inflammation. The technique of barometric whole body plethysmography for cats was combined with a system to condense the effluent air from the plethysmograph, allowing simultaneous EBC collection and respiratory pattern measurement. H(2)O(2) was determined spectrophotometrically. Eighteen experimental cats were used to investigate the impact on EBC volume and EBC H(2)O(2) of plethysmograph ventilation rate, collection duration, sample stability, within-day and day-to-day variability. After determination of a standardised EBC collection procedure, correlation analyses between EBC H(2)O(2) and bronchoalveolar lavage (BAL) cytology of healthy and allergen-challenged Ascaris suum (AS)-sensitised cats were performed. A significant and positive correlation between EBC H(2)O(2) and bronchoalveolar lavage (BAL) neutrophil% was found in healthy cats (P < 0.001, r = 0.55), whereas in AS-sensitised cats, correlation with BAL eosinophil% was significant (P < 0.005, r = 0.61). H(2)O(2) was increased after an allergen challenge in AS-sensitised cats (n = 6, 0.56+/-0.12 versus 1.08+/-0.35 micromol/L, P < 0.05). This study proposes a non-invasive, well tolerated and repeatable method of EBC collection for cats and suggests that EBC H(2)O(2) might be used as non-invasive biomarker for monitoring lower airway inflammation. PMID:15848781

  19. Salivary biochemical markers as potential acute toxicity parameters for acute radiation injury: A study on small experimental animals.

    PubMed

    Soni, S; Agrawal, P; Kumar, N; Mittal, G; Nishad, D K; Chaudhury, N K; Bhatnagar, A; Basu, M; Chhillar, N

    2016-03-01

    Researchers have been evaluating several biodosimetric/screening approaches to assess acute radiation injury, related to mass causality. Keeping in mind this background, we hypothesized that effect of whole-body irradiation in single fraction in graded doses can affect the secretion of various salivary components that could be used as acute radiation injury/toxicity marker, which can be used in screening of large population at the time of nuclear accidents/disaster. Thirty Sprague Dawley rats treated with whole-body cobalt-60 gamma irradiation of dose 1-5 Gy (dose rate: 0.95 Gy/min) were included in this study. Whole mixed saliva was collected from all animals before and after radiation up to 72 h postradiation. Saliva was analyzed for electrolytes, total protein, urea, and amylase. Intragroup comparison of salivary parameters at different radiation doses showed significant differences. Potassium was significantly increased as the dose increased from 1 Gy to 5 Gy (p < 0.01) with effect size of difference (r > 0.5). Sodium was significantly altered after 3-5 Gy (p < 0.01, r > 0.5), except 1 and 2 Gy, whereas changes in sodium level were nonsignificant (p > 0.5). Urea, total protein, and amylase levels were also significantly increased as the radiation dose increased (p < 0.01) with large effect size of difference (r > 0.5). This study suggests that salivary parameters were sensitive toward radiation even at low radiation dose which can be used as a predictor of radiation injury. PMID:25813962

  20. Generalized and Specific Cognitive Performance in Clinical High-Risk Cohorts: A Review Highlighting Potential Vulnerability Markers for Psychosis

    PubMed Central

    Brewer, Warrick J.; Wood, Stephen J.; Phillips, Lisa J.; Francey, Shona M.; Pantelis, Christos; Yung, Alison R.; Cornblatt, Barbara; McGorry, Patrick D.

    2006-01-01

    Cognitive deficits are a core feature of established psychotic illnesses. However, the association between cognition and emerging psychosis is less understood. While there is some evidence that cognitive deficits are present prior to the onset of psychosis, findings are not consistent. In this article we provide an overview of the more general cognitive findings available from genetic high-risk studies, retrospective studies, and birth cohort studies. We then focus the review on neuropsychological performance in clinically “at-risk” groups. Overall, general cognitive ability as assessed by established batteries appears to remain relatively intact in these ultra-high risk cohorts and is a poor predictor close to illness onset relative to other vulnerability factors. Further decline may occur with illness progression, more consistent with state relative to trait factors. In addition, most established cognitive tasks involve several relatively discrete cognitive subprocesses, where findings from general batteries of subtests may mask specific deficits. In this context, our review suggests that relatively specific olfactory identification and spatial working memory deficits exist prior to illness onset and may be more potent trait markers for psychosis than cognitively dense tasks such as verbal memory. Suggestions for further research address the importance of standardization of inclusion criteria and the maintenance of basic neuropsychological assessment to allow better comparison of findings across centers. Further, in order to better understand the aetiopathology of cognitive dysfunction in psychosis, more experimental, hypothesis-driven measures of discrete cognitive processes are required. Delineation of the relationship between specific cognitive ability and symptoms from data-driven approaches may improve our understanding of the role of cognition during psychosis onset. PMID:16782759

  1. The effects of oral Cardax (disodium disuccinate astaxanthin) on multiple independent oxidative stress markers in a mouse peritoneal inflammation model: influence on 5-lipoxygenase in vitro and in vivo.

    PubMed

    Lockwood, Samuel F; Penn, Marc S; Hazen, Stanley L; Bikádi, Zsolt; Zsila, Ferenc

    2006-06-01

    Disodium disuccinate astaxanthin ('rac'-dAST; Cardax) is a water-dispersible C40 carotenoid derivative under development for oral and parenteral administration for cardioprotection of the at-risk ischemic cardiovascular patient. In experimental infarction models in animals (rats, rabbits, and dogs), significant myocardial salvage has been obtained, up to 100% at the appropriate dose in dogs. The documented mechanism of action in vitro includes direct scavenging of biologically produced superoxide anion; in vivo in rabbits, modulation of the complement activity of serum has also been shown. A direct correlation between administration of the test compound in animals and reductions of multiple, independent markers of oxidative stress in serum was recently obtained in a rat experimental infarction model. For the current study, it was hypothesized that oral Cardax administration would inhibit oxidative damage of multiple relevant biological targets in a representative, well-characterized murine peritoneal inflammation model. A previously developed mass spectrometry-based (LC/ESI/MS/MS) approach was used to interrogate multiple distinct pathways of oxidation in a black mouse (C57/BL6) model system. In vivo markers of oxidant stress from peritoneal lavage samples (supernatants) were evaluated in mice on day eight (8) after treatment with either Cardax or vehicle (lipophilic emulsion without drug) orally by gavage at 500 mg/kg once per day for seven (7) days at five (5) time points: (1) baseline prior to treatment (t=0); (2) 16 h following intraperitoneal (i.p.) injection with thioglycollate to elicit a neutrophilic infiltrate; (3) 4 h following i.p. injection of yeast cell wall (zymosan; t=16 h/4 h thioglycollate+zymosan); (4) 72 h following i.p. injection with thioglycollate to elicit monocyte/macrophage infiltration; and (5) 72 h/4 h thioglycollate+zymosan. A statistically significant sparing effect on the arachidonic acid (AA) and linoleic acid (LA) substrates was

  2. Selectable markers with potential activity against insects, plus other insect-oriented strategies for mycotoxin reduction in Midwest corn

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reduction of insect damage has the potential to greatly reduce the levels of mycotoxins in corn, as studies with Bt corn have shown. However, the large number of insect species involved necessitates the development of comprehensive insect control to most effectively utilize this strategy. One stra...

  3. Assessment in Higher Education: The Potential for a Community of Practice to Improve Inter-Marker Reliability

    ERIC Educational Resources Information Center

    Herbert, Ian P.; Joyce, John; Hassall, Trevor

    2014-01-01

    The design, delivery and assessment of a complete educational scheme, such as a degree programme or a professional qualification course, is a complex matter. Maintaining alignment between the stated aims of the curriculum and the scoring of student achievement is an overarching concern. The potential for drift across individual aspects of an…

  4. Identification of alpha-1 acid glycoprotein (AGP) as a potential marker of impaired growth in the newborn piglet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two studies were conducted to investigate the relationship between the circulating levels of the acute phase proteins haptoglobin (HP) and alpha 1 acid glycoprotein (AGP) and growth potential in neonatal pigs. In runts, the circulating level of AGP, but not HP in serum of newborn piglets was higher...

  5. [Organization of public oral health services for early diagnosis of potentially malignant disorders in the state of Rio de Janeiro, Brazil].

    PubMed

    Casotti, Elisete; Monteiro, Ana Beatriz Fonseca; Castro Filho, Evelyn Lima de; Santos, Manuella Pires Dos

    2016-05-01

    This is a study of the organization of public health services in the state of Rio de Janeiro concerning the diagnosis of potentially malignant disorders. Secondary data from the database of the first phase of the Program for Enhancement for Access to and Quality of Primary Care were used. The implementation of actions at different levels for cancer prevention, the availability of diagnostic support services and the organization of the care network were assessed. The results show that only 58.8% of oral health teams record and monitor suspect cases; that only 47.1% reported having preferential channels for referring patients and there is great variation in waiting times to confirm the diagnosis. Local managerial and regional support actions can improve the organization of the care network for oral cancer prevention in the state. PMID:27166905

  6. 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

  7. Spatial variation in fatty acid trophic markers in albacore tuna from the southwestern Pacific Ocean-A potential 'tropicalization' signal

    NASA Astrophysics Data System (ADS)

    Parrish, Christopher C.; Pethybridge, Heidi; Young, Jock W.; Nichols, Peter D.

    2015-03-01

    Signature fatty acids were used to explore trophic variations in albacore and skipjack tuna sampled from the southwestern Pacific Ocean. There were clear spatial differences in fatty acid profiles between albacore sampled in the Coral (tropical zone centered at ~20°S) and Tasman (temperate zone centered at ~42°S) Seas; however, few differences were observed in fatty acid profiles of albacore sampled off Tasmania and New Zealand. Fatty acid signatures of the Tasman Sea samples reflected a food web based more on diatoms and included: 20:5ω3 (EPA), 18:1ω7, 22:1ω11, 18:2ω6, 18:4ω3, 18:3ω3, and 20:4ω3. In contrast, albacore from the Coral Sea had a distinct fatty acid signature which included 20:4ω6, 22:5ω6, 17:0, 22:4ω6, 24:0, and 17:1. Multivariate analyses revealed the importance of 22:6ω3 (DHA) in Coral Sea-caught albacore which also had a DHA/EPA ratio more than twice that in all other groups suggesting a greater dinoflagellate contribution and/or a higher trophic position. Fatty acid markers indicative of krill consumption were significantly higher in temperate-caught albacore although skipjack were closest in fatty acid composition to krill. These results were likely due to differences at the base of the food web in these two seas suggesting that signature fatty acids can be used as indicators of ecosystem change: in this case the gradual 'tropicalization' of the eastern seaboard of Australia through the southward extension of the East Australian Current. Our findings also indicate comparatively lower concentrations of healthful ω3 long-chain polyunsaturated fatty acids, in particular the content of DHA and EPA, in the tropical samples. This suggests that tropicalization could adversely affect the dietary intake of albacore and other marine predators in the region. Such changes are readily detectable by fatty acid analysis.

  8. Quantitative analyses of T2-weighted MRI as a potential marker for response to somatostatin analogs in newly diagnosed acromegaly.

    PubMed

    Heck, Ansgar; Emblem, Kyrre E; Casar-Borota, Olivera; Bollerslev, Jens; Ringstad, Geir

    2016-05-01

    In growth hormone (GH)-producing adenomas, T2-weighted MRI signal intensity is a marker for granulation pattern and response to somatostatin analogs (SSA). Prediction of treatment response is necessary for individualized treatment, and T2 intensity assessment might improve preoperative classification of somatotropinomas. The objectives of this study are (I) to explore the feasibility of quantitative T2-weighted MRI histogram analyses in newly diagnosed somatotroph adenomas and their relation to clinical and histological parameters and (II) to compare the quantitative method to conventional, visual assessment of T2 intensity. The study was a retrospective cohort study of 58 newly diagnosed patients. In 34 of these, response to primary SSA treatment after median 6 months was evaluated. Parameters from the T2 histogram analyses (T2 intensity ratio and T2 homogeneity ratio) were correlated to visually assessed T2 intensity (hypo-, iso-, hyperintense), baseline characteristics, response to SSA treatment, and histological granulation pattern (anti-Cam5.2). T2 intensity ratio was lowest in the hypointense tumors and highest in the hyperintense tumors (0.66 ± 0.10 vs. 1.07 ± 0.11; p < 0.001). T2 intensity at baseline correlated with reduction in GH (r = -0.67; p < 0.001) and IGF-1 (r = -0.36; p = 0.037) after primary SSA treatment (n = 34). The T2 homogeneity ratio correlated with adenoma size reduction (r = -0.45; p = 0.008). Sparsely granulated adenomas had a higher T2 intensity than densely or intermediately granulated adenomas. T2 histogram analyses are an applicable tool to assess T2 intensity in somatotroph adenomas. Quantitatively assessed T2 intensity ratio in GH-producing adenomas correlates with conventional assessment of T2 intensity, baseline characteristics, response to SSA treatment, and histological granulation pattern. PMID:26475495

  9. Potential role of chemo-radiation with oral capecitabine in a breast cancer patient with central nervous system relapse.

    PubMed

    Hikino, Hajime; Yamada, Takako; Johbara, Kanta; Obayashi, Nobuhiko; Ozaki, Nobuhiro

    2006-02-01

    A 54-year-old woman underwent mastectomy and axillary lymph node dissection for infiltrating ductal carcinoma with multiple lymph node involvement. The patient received adriamycin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) (AC) followed by weekly paclitaxel 80 mg/m(2) and external irradiation to the local lymph node regions as adjuvant treatment. After 1 year and 5 months, the patient suffered her first recurrence, developing multiple brain and meningeal metastases. CNS involvement was well controlled by oral capecitabine (2400 mg twice daily, on days 1-21 of a 28-day cycle) and external whole brain irradiation of 50 Gy with minimal toxicity. We suggest that capecitabine contributed to the favorable clinical course in this patient and believe that, as an oral agent, this drug may benefit patients with CNS metastases of breast cancer by allowing home-based therapy. PMID:16005228

  10. RAPD and SCAR markers as potential tools for detection of milk origin in dairy products: Adulterant sheep breeds in Serra da Estrela cheese production.

    PubMed

    Cunha, Joana T; Ribeiro, Tânia I B; Rocha, João B; Nunes, João; Teixeira, José A; Domingues, Lucília

    2016-11-15

    Serra da Estrela Protected Designation of Origin (PDO) cheese is the most famous Portuguese cheese and has a high commercial value. However, the adulteration of production with cheaper/lower-quality milks from non-autochthones ovine breeds compromises the quality of the final product and undervalues the original PDO cheese. A Randomly Amplified Polymorphic DNA (RAPD) method was developed for efficient detection of adulterant breeds in milk mixtures used for fraudulent production of this cheese. Furthermore, Sequence Characterized Amplified Region (SCAR) markers were designed envisioning the detection of milk adulteration in processed dairy foods. The RAPD-SCAR technique is here described, for the first time, to be potentially useful for detection of milk origin in dairy products. In this sense, our findings will play an important role on the valorization of Serra da Estrela cheese, as well as on other high-quality dairy products prone to adulteration, contributing to the further development of the dairy industry. PMID:27283677

  11. Fructose-bisphosphate aldolase a is a potential metastasis-associated marker of lung squamous cell carcinoma and promotes lung cell tumorigenesis and migration.

    PubMed

    Du, Sha; Guan, Zhuzhu; Hao, Lihong; Song, Yang; Wang, Lan; Gong, Linlin; Liu, Lu; Qi, Xiaoyu; Hou, Zhaoyuan; Shao, Shujuan

    2014-01-01

    Fructose-bisphosphate aldolase A (ALDOA) is a key enzyme in glycolysis and is responsible for catalyzing the reversible conversion of fructose-1,6-bisphosphate to glyceraldehydes-3-phosphate and dihydroxyacetone phosphate. ALDOA contributes to various cellular functions such as muscle maintenance, regulation of cell shape and mobility, striated muscle contraction, actin filament organization and ATP biosynthetic process. Here, we reported that ALDOA is a highly expressed in lung squamous cell carcinoma (LSCC) and its expression level is correlated with LSCC metastasis, grades, differentiation status and poor prognosis. Depletion of ALDOA expression in the lung squamous carcinoma NCI-H520 cells reduces the capabilities of cell motility and tumorigenesis. These data suggest that ALDOA could be a potential marker for LSCC metastasis and a therapeutic target for drug development. PMID:24465716

  12. Fructose-Bisphosphate Aldolase A Is a Potential Metastasis-Associated Marker of Lung Squamous Cell Carcinoma and Promotes Lung Cell Tumorigenesis and Migration

    PubMed Central

    Hao, Lihong; Song, Yang; Wang, Lan; Gong, Linlin; Liu, Lu; Qi, Xiaoyu; Hou, Zhaoyuan; Shao, Shujuan

    2014-01-01

    Fructose-bisphosphate aldolase A (ALDOA) is a key enzyme in glycolysis and is responsible for catalyzing the reversible conversion of fructose-1,6-bisphosphate to glyceraldehydes-3-phosphate and dihydroxyacetone phosphate. ALDOA contributes to various cellular functions such as muscle maintenance, regulation of cell shape and mobility, striated muscle contraction, actin filament organization and ATP biosynthetic process. Here, we reported that ALDOA is a highly expressed in lung squamous cell carcinoma (LSCC) and its expression level is correlated with LSCC metastasis, grades, differentiation status and poor prognosis. Depletion of ALDOA expression in the lung squamous carcinoma NCI-H520 cells reduces the capabilities of cell motility and tumorigenesis. These data suggest that ALDOA could be a potential marker for LSCC metastasis and a therapeutic target for drug development. PMID:24465716

  13. 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

  14. Mechanisms of the harmful effects of bacterial semen infection on ejaculated human spermatozoa: potential inflammatory markers in semen.

    PubMed

    Fraczek, Monika; Kurpisz, Maciej

    2015-01-01

    The invasion of the male reproductive tract by microorganisms, and its subsequent consequences for sperm fertilizing potential, has been intensely discussed. The role of the bacteria that are responsible for the colonization and contamination of the male urogenital tract, rather than its infection, in diminished sperm parameters raises the most controversy. There are numerous premises suggesting that bacterial semen infection is associated with male infertility. However, the molecular mechanism by which the fertility is affected is complex and multifactorial, and still presents a puzzle. Some authors have suggested that direct interactions between bacteria and human spermatozoa facilitate sperm immobilization, affect sperm morphology, and thus weaken the ability of sperm to fertilize. On the other hand, the massive infiltration of activated leukocytes into the inflammatory site may be associated with impairment of sperm fertilizing potential, due to oxidative, apoptotic, and immune processes. This review presents current research trends and aims to summarize the present knowledge of semen inflammation and causative bacterial agents in the male urogenital tract, with its consequence on seminological parameters, and male fertility status. PMID:26306512

  15. Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease.

    PubMed

    Olcese, James M; Cao, Chuanhai; Mori, Takashi; Mamcarz, Malgorzata B; Maxwell, Anne; Runfeldt, Melissa J; Wang, Li; Zhang, Chi; Lin, Xiaoyang; Zhang, Guixin; Arendash, Gary W

    2009-08-01

    The neurohormone melatonin has been reported to exert anti-beta-amyloid aggregation, antioxidant, and anti-inflammatory actions in various in vitro and animal models. To comprehensively determine the potential for long-term melatonin treatment to protect Alzheimer's transgenic mice against cognitive impairment and development of beta-amyloid (Abeta) neuropathology, we administered melatonin (100 mg/L drinking water) to APP + PS1 double transgenic (Tg) mice from 2-2.5 months of age to their killing at age 7.5 months. A comprehensive behavioral battery administered during the final 6 weeks of treatment revealed that Tg mice given melatonin were protected from cognitive impairment in a variety of tasks of working memory, spatial reference learning/memory, and basic mnemonic function; Tg control mice remained impaired in all of these cognitive tasks/domains. Immunoreactive Abeta deposition was significantly reduced in hippocampus (43%) and entorhinal cortex (37%) of melatonin-treated Tg mice. Although soluble and oligomeric forms of Abeta1-40 and 1-42 were unchanged in the hippocampus and cortex of the same melatonin-treated Tg mice, their plasma Abeta levels were elevated. These Abeta results, together with our concurrent demonstration that melatonin suppresses Abeta aggregation in brain homogenates, are consistent with a melatonin-facilitated removal of Abeta from the brain. Inflammatory cytokines such as tumor necrosis factor (TNF)-alpha were decreased in hippocampus (but not plasma) of Tg+ melatonin mice. Finally, the cortical mRNA expression of three antioxidant enzymes (SOD-1, glutathione peroxidase, and catalase) was significantly reduced to non-Tg levels by long-term melatonin treatment in Tg mice. Thus, melatonin's cognitive benefits could involve its anti-Abeta aggregation, anti-inflammatory, and/or antioxidant properties. Our findings provide support for long-term melatonin therapy as a primary or complementary strategy for abating the progression of

  16. 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

  17. Gene Expression Changes in Phosphorus Deficient Potato (Solanum tuberosum L.) Leaves and the Potential for Diagnostic Gene Expression Markers

    PubMed Central

    Hammond, John P.; Broadley, Martin R.; Bowen, Helen C.; Spracklen, William P.; Hayden, Rory M.; White, Philip J.

    2011-01-01

    Background There are compelling economic and environmental reasons to reduce our reliance on inorganic phosphate (Pi) fertilisers. Better management of Pi fertiliser applications is one option to improve the efficiency of Pi fertiliser use, whilst maintaining crop yields. Application rates of Pi fertilisers are traditionally determined from analyses of soil or plant tissues. Alternatively, diagnostic genes with altered expression under Pi limiting conditions that suggest a physiological requirement for Pi fertilisation, could be used to manage Pifertiliser applications, and might be more precise than indirect measurements of soil or tissue samples. Results We grew potato (Solanum tuberosum L.) plants hydroponically, under glasshouse conditions, to control their nutrient status accurately. Samples of total leaf RNA taken periodically after Pi was removed from the nutrient solution were labelled and hybridised to potato oligonucleotide arrays. A total of 1,659 genes were significantly differentially expressed following Pi withdrawal. These included genes that encode proteins involved in lipid, protein, and carbohydrate metabolism, characteristic of Pi deficient leaves and included potential novel roles for genes encoding patatin like proteins in potatoes. The array data were analysed using a support vector machine algorithm to identify groups of genes that could predict the Pi status of the crop. These groups of diagnostic genes were tested using field grown potatoes that had either been fertilised or unfertilised. A group of 200 genes could correctly predict the Pi status of field grown potatoes. Conclusions This paper provides a proof-of-concept demonstration for using microarrays and class prediction tools to predict the Pi status of a field grown potato crop. There is potential to develop this technology for other biotic and abiotic stresses in field grown crops. Ultimately, a better understanding of crop stresses may improve our management of the crop, improving

  18. Oral Cancer

    MedlinePlus

    ... HUMAN SERVICES National Institutes of Health About Oral Cancer Oral cancer includes cancers of the mouth and pharynx (the back of the throat). Oral cancer accounts for roughly two percent of all cancers ...

  19. 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

  20. Lateral ventricular cerebrospinal fluid diffusivity as a potential neuroimaging marker of brain temperature in multiple sclerosis: a hypothesis and implications.

    PubMed

    Hasan, Khader M; Lincoln, John A; Nelson, Flavia M; Wolinsky, Jerry S; Narayana, Ponnada A

    2015-04-01

    In this retrospective study we tested the hypothesis that the net effect of impaired electrical conduction and therefore increased heat dissipation in multiple sclerosis (MS) results in elevated lateral ventricular (LV) cerebrospinal fluid (CSF) diffusivity as a measure of brain temperature estimated in vivo using diffusion tensor imaging (DTI). We used validated DTI-based segmentation methods to obtain normalized LV-CSF volume and its corresponding CSF diffusivity in 108 MS patients and 103 healthy controls in the age range of 21-63 years. The LV CSF diffusivity was ~2% higher in MS compared to controls that correspond to a temperature rise of ~1°C that could not be explained by changes in the CSF viscosity due to altered CSF protein content in MS. The LV diffusivity decreased with age in healthy controls (r=-0.29; p=0.003), but not in MS (r=0.15; p=0.11), possibly related to MS pathology. Age-adjusted LV diffusivity increased with lesion load (r=0.518; p=1×10(-8)). Our data suggest that the total brain lesion load is the primary contributor to the increase in LV CSF diffusivity in MS. These findings suggest that LV diffusivity is a potential in vivo biomarker of the mismatch between heat generation and dissipation in MS. We also discuss limitations and possible confounders. PMID:25485790

  1. Comparative study of Saccharomyces cerevisiae wine strains to identify potential marker genes correlated to desiccation stress tolerance.

    PubMed

    Capece, Angela; Votta, Sonia; Guaragnella, Nicoletta; Zambuto, Marianna; Romaniello, Rossana; Romano, Patrizia

    2016-05-01

    The most diffused formulation of starter for winemaking is active dry yeast (ADY). ADYs production process is essentially characterized by air-drying stress, a combination of several stresses, including thermal, hyperosmotic and oxidative and cell capacity to counteract such multiple stresses will determine its survival. The molecular mechanisms underlying cell stress response to desiccation have been mostly studied in laboratory and commercial yeast strains, but a growing interest is currently developing for indigenous yeast strains which represent a valuable and alternative source of genetic and molecular biodiversity to be exploited. In this work, a comparative study of different Saccharomyces cerevisiae indigenous wine strains, previously selected for their technological traits, has been carried out to identify potentially relevant genes involved in desiccation stress tolerance. Cell viability was evaluated along desiccation treatment and gene expression was analyzed by real-time PCR before and during the stress. Our data show that the observed differences in individual strain sensitivity to desiccation stress could be associated to specific gene expression over time. In particular, either the basal or the stress-induced mRNA levels of certain genes, such as HSP12, SSA3, TPS1, TPS2, CTT1 and SOD1, result tightly correlated to the strain survival advantage. This study provides a reliable and sensitive method to predict desiccation stress tolerance of indigenous wine yeast strains which could be preliminary to biotechnological applications. PMID:26882930

  2. Potential Markers of Aggressive Behavior: The Fear of Other Persons' Laughter and Its Overlaps with Mental Disorders

    PubMed Central

    Weiss, Elisabeth M.; Schulter, Günter; Freudenthaler, H. Harald; Hofer, Ellen; Pichler, Natascha; Papousek, Ilona

    2012-01-01

    Background Anecdotal evidence suggested that some outbreaks of aggression and violence may be related to a fear of being laughed at and ridiculed. The present study examined the potential association of the fear of other persons' laughter (gelotophobia) with emotion-related deficits predisposing for aggression, anger and aggression proneness, and its overlaps with relevant mental disorders. Methodology/Principal Findings Gelotophobic individuals were compared to a non-phobic control group with respect to emotion regulation skills and strategies, alexithymia, anger proneness, and aggressive behavior. Social phobia was diagnosed using the Structural Clinical Interview (SCID-I) for DSM IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). Additionally, the SCID-II modules for Cluster A Personality Disorders, which includes schizoid, paranoid, and schizotypal personality disorder were administered to all participants. The findings show that gelotophobia is associated with deficits in the typical handling of an individual's own affective states, greater anger proneness and more aggressive behavior according to self-report as compared to non-phobic individuals. 80% of the subjects in the gelotophobia group had an additional diagnosis of social phobia and/or Cluster A personality disorder. The additional diagnoses did not predict additional variance of anger or aggressive behavior as compared to gelotophobia alone. Conclusions/Significance Features related to aggression and violence that are inherent in mental disorders such as social phobia and Cluster A personality disorders may be particularly evident in the symptom of fear of other persons' laughter. PMID:22675438

  3. Intervarietal variations in various oxidative stress markers and antioxidant potential of finger millet (Eleusine coracana) subjected to drought stress.

    PubMed

    Bartwal, Arti; Pande, Anjali; Sharma, Priyadarshini; Arora, Sandeep

    2016-07-01

    Drought is a major form of abiotic stress leading to lower crop productivity. Experiment was carried out for selecting the most tolerant genotype among six different genotypes of finger millet under drought stress. Seeds of six finger millet genotypes were sown in pots and grown for 35 days. After this period, drought was induced by withholding watering for stressed plants while control plants were watered regularly for comparison. Among all six different varieties of finger millet screened (PR202, PES400, PRM6107, VL283, VL328 and VL149) under varying intensities of drought stress,PRM6107 and PR202 showed highest stress tolerance by limiting excessive accumulation of reactive oxygen species (ROS) through activation of ROS scavenging antioxidative enzymes. A 200% increase in ascorbate content was recorded in PRM6107 and PR202, while in other varieties limited increase in ascorbate content was observed. Maximum decrease in chlorophyll content was observed in VL328 (83%) while least drop was observed in VL149 (65%). Relative water content indicated that PR202 was able to retain maximum water content under stress, as it recorded least drop in relative water content (55%), contributing to its better survival under stress. In conclusion finger millet genotypes PRM6107 and PR202 possessed maximum drought tolerance potential and thus may be used for allele mining of drought tolerant genes, which can further be employed for the development of more drought stress tolerant staple crops using biotechnological approach. PMID:27498495

  4. Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells

    PubMed Central

    Armitage, Emily G.; Kotze, Helen L.; Allwood, J. William; Dunn, Warwick B.; Goodacre, Royston; Williams, Kaye J.

    2015-01-01

    Hypoxia inducible factors (HIFs) plays an important role in oxygen compromised environments and therefore in tumour survival. In this research, metabolomics has been applied to study HIFs metabolic function in two cell models: mouse hepatocellular carcinoma and human colon carcinoma, whereby the metabolism has been profiled for a range of oxygen potentials. Wild type cells have been compared to cells deficient in HIF signalling to reveal its effect on cellular metabolism under normal oxygen conditions as well as low oxygen, hypoxic and anoxic environments. Characteristic responses to hypoxia that were conserved across both cell models involved the anti-correlation between 2-hydroxyglutarate, 2-oxoglutarate, fructose, hexadecanoic acid, hypotaurine, pyruvate and octadecenoic acid with 4-hydroxyproline, aspartate, cysteine, glutamine, lysine, malate and pyroglutamate. Further to this, network-based correlation analysis revealed HIF specific pathway responses to each oxygen condition that were also conserved between cell models. From this, 4-hydroxyproline was revealed as a regulating hub in low oxygen survival of WT cells while fructose appeared to be in HIF deficient cells. Pathways surrounding these hubs were built from the direct connections of correlated metabolites that look beyond traditional pathways in order to understand the mechanism of HIF response to low oxygen environments. PMID:26508589

  5. P16(INK4a) expression as a potential prognostic marker in cervical pre-neoplastic and neoplastic lesions.

    PubMed

    Queiroz, Conceição; Silva, Tânia Correia; Alves, Venâncio A F; Villa, Luisa L; Costa, Maria Cecília; Travassos, Ana Gabriela; Filho, José Bouzas Araújo; Studart, Eduardo; Cheto, Tatiana; de Freitas, Luiz Antonio R

    2006-01-01

    An immunohistochemical analysis with monoclonal antibody p16(INK4a) was performed in formalin-fixed, paraffin-embedded samples of 60 cases. The aim was to investigate in biopsies the expression of p16(INK4a) of normal uterine cervical tissue, pre-cancerous and cancerous lesions, and their relation with human papilloma virus (HPV) and HIV status. Three parameters were evaluated: percentage of p16(INK4a) positive cells, reaction intensity, and cell staining pattern. All of these parameters were statistically different when compared among different histological groups. However, logistic regression model showed that the reaction intensity was the best indicator of the expression of p16(INK4a). This expression increases from normal to invasive squamous carcinoma. Sixty-six percent of the patients with CIN grade 1 (CIN1) expressed p16(INK4a) (all these cases were infected with high risk HPV). Our study supports the hypothesis that p16(INK4a) expression in pre-cancerous lesions and cancers can be used to identify HPV-transformed cells. Of great interest for routine diagnostic use is the fact that immunohistochemical testing for p16(INK4a) seems to be capable of identifying HPV-positive cells and potentially recognizing those lesions with an increased risk of progression to high-grade lesions. PMID:16376485

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

    PubMed Central

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

    2013-01-01

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

  7. 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

  8. 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

  9. Proteomic analysis of human papillomavirus-related oral squamous cell carcinoma: identification of thioredoxin and epidermal-fatty acid binding protein as upregulated protein markers in microdissected tumor tissue.

    PubMed

    Melle, Christian; Ernst, Günther; Winkler, Robert; Schimmel, Bettina; Klussmann, Jens Peter; Wittekindt, Claus; Guntinas-Lichius, Orlando; von Eggeling, Ferdinand

    2009-04-01

    Human papillomavirus (HPV) infection has been identified as an etiologic agent for a subset of oral squamous cell carcinoma (OSCC) with increasing incidence. HPV DNA-positivity may confer better prognosis but the related oncogenic mechanisms are unknown. For the identification of HPV relevant proteins, we analyzed microdissected cells from HPV DNA-positive (n = 17) and HPV DNA-negative (n = 7) OSCC tissue samples. We identified 18 proteins from tumor tissues by peptide fingerprint mapping and SELDI MS that were separated using 2-DE. Among a number of signals that were detected as significantly different in the protein profiling analysis, we identified thioredoxin (TRX) and epidermal-fatty acid binding protein as upregulated in HPV related tumor tissue. This study, investigating for the first time proteomic changes in microdissected HPV infected tumor tissue, provides an indication on the oncogenic potential of viruses. PMID:19337991

  10. Identification of 14-3-3zeta associated protein networks in oral cancer.

    PubMed

    Matta, Ajay; Masui, Olena; Siu, K W Michael; Ralhan, Ranju

    2016-04-01

    Advancements in genomics, proteomics, and bioinformatics have improved our understanding of gene/protein networks involved in intra- and intercellular communication and tumor-host interactions. Using proteomics integrated with bioinformatics, previously we reported overexpression of 14-3-3ζ in premalignant oral lesions and oral squamous cell carcinoma tissues in comparison with normal oral epithelium. 14-3-3ζ emerged as a novel molecular target for therapeutics and a potential prognostic marker in oral squamous cell carcinoma patients. However, the role of 14-3-3ζ in development and progression of oral cancer is not known yet. This study aimed to identify the 14-3-3ζ associated protein networks in oral cancer cell lines using IP-MS/MS and bioinformatics. A total of 287 binding partners of 14-3-3ζ were identified in metastatic (MDA1986) and nonmetastatic (SCC4) oral cancer cell lines including other 14-3-3 isoforms (2%), proteins involved in apoptosis (2%), cytoskeleton (9%), metabolism (16%), and maintenance of redox potential (2%). Our bioinformatics analysis revealed involvement of 14-3-3ζ in protein networks regulating cell cycle, proliferation, apoptosis, cellular trafficking, and endocytosis in oral cancer. In conclusion, our data revealed several novel protein interaction networks involving 14-3-3ζ in oral cancer progression and metastasis. PMID:26857332

  11. Markers of vulnerability in schizophrenia

    PubMed Central

    Prelipceanu, D

    2009-01-01

    Vulnerability in schizophrenia is an integrative concept, which tries to explain the development of schizophrenia as an interaction between different individual susceptibility factors and environmental risk factors. Vulnerability markers used in genetic studies include biochemical indicators, neuroanatomical, neurophysiologic, and cognitive abnormalities. Among those, the most extensive studied markers were: evoked potentials, smooth pursuit eye movements, and attentional deficits. Some of the potential indicators presented in this paper satisfy most of the criteria necessary for a vulnerability marker, but none meets all of them. Nevertheless, they represent important markers of risk to schizophrenia. Key words: vulnerability, evoked potentials, eye movements, attentional deficits PMID:20108534

  12. Surrogate markers for cerebral blood flow correlate with [¹⁸F]-fallypride binding potential at dopamine D(2/3) receptors in human striatum.

    PubMed

    Cumming, Paul; Xiong, Guoming; la Fougère, Christian; Rominger, Axel; Bartenstein, Peter; Buchholz, Hans-Georg; Piel, Markus; Rösch, Frank; Gründer, Gerhard; Vernaleken, Ingo

    2013-04-01

    Positron emission tomography (PET) with the high affinity dopamine D(2/3) receptor ligand [¹⁸F]-fallypride affords estimates of the binding potential (BP(ND) ) in extra-striatal regions of low receptor abundance, but the sufficient recording time for accurate measurements in striatum has been called into question. We have earlier argued that transient equilibrium measurements are obtained in striatum with [¹⁸F]-fallypride PET recordings of 3 h duration, which may be the practical limit for clinical investigations without interrupted scanning. However, the high extraction fraction of [¹⁸F]-fallypride predicts flow-dependence of tracer delivery to brain, which may be a source of variance of the apparent BP(ND) in regions of high binding. To test this prediction, we conducted a retrospective analysis of [¹⁸F]-fallypride PET data from a group of 50 healthy volunteers (age 18-58 years [mean ± SD: 32.6 ± 10.6), who had participated in clinical studies without arterial input measurements. We used the initial 120-s integral (AUC) of the venous confluence (VC) as a surrogate marker for cerebral blood flow (CBF) and tested for correlations between regional estimates of BP(ND) calculated by the simplified reference tissue model (SRTM) and the individual VC-AUC. The magnitude of BP(ND) in a high binding region (putamen), but not in a low binding region (thalamus) correlated positively with VC-AUC, suggesting that approximately 9% of the variance in the [¹⁸F]-fallypride BP(ND) in putamen can be attributed to individual differences in this surrogate marker for CBF, a contribution equal in magnitude to the effects of age on BP(ND) in putamen of the present healthy control group. PMID:23239525

  13. 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 PKCαβ. 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

  14. 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

  15. Proinflammatory cytokine levels in oral lichen planus, oral leukoplakia, and oral submucous fibrosis

    PubMed Central

    Jacobs, Reinhilde

    2015-01-01

    Objectives The objective of this study was to identify salivary and serum concentrations of interleukin (IL)-8, IL-6, and tumor necrosis factor alpha (TNF-α) in patients with oral lichen planus, oral leukoplakia, oral submucous fibrosis, and healthy controls. Materials and Methods Patients selected included 54 oral lichen planus (41 to 65 years), 50 oral leukoplakia (42 to 65 years), 51 oral submucous fibrosis (41 to 65 years), and 50 healthy controls (42 to 65 years). Oral lichen