Molecular Classification of HPV-Associated Head Neck Cancer

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P91-P91
Author(s):  
Paul M. Weinberger ◽  
Ziwei Yu ◽  
Panteleimon Kountourakis ◽  
Clarence T Sasaki ◽  
Diane Kowalski ◽  
...  
Keyword(s):  
Hierarchical Clustering ◽  
Clustering Analysis ◽  
Class Ii ◽  
Class I ◽  
Hierarchical Clustering Analysis ◽  
Class Iii ◽  
Class Model ◽  
Hpv Dna ◽  
Clustering Patterns ◽  
P16 Expression

Problem We previously proposed that head and neck squamous cell carcinoma (HNSCC) presents in three histopathologically similar but molecularly distinct types where p16 expression combined with high-risk Human Papillomavirus (HPV) presence defines three distinct subgroups: Class I (HPV-), Class II (HPV16+/p16-), Class III (HPV16+/p16+). In this study we sought to further explore and validate this classification schema. Methods Paraffin-embedded specimens from 77 patients with OSCC classified into the 3-class model based on p16 expression and HPV DNA presence were previously queried for expression of 14 target proteins with known involvement in tumor progression using AQUA(tm). We calculated pairwise associations by Spearman correlation and performed hierarchical clustering analysis to assess global expression patterns of class I, II and III tumors. Results Hierarchical clustering analysis demonstrated class I and class II tumors displayed similar clustering patterns. Class III tumors (HPV+/p16+) displayed unique clustering patterns distinct from both class I and class II tumors. In class I/II tumors ERK2, p27, p14, ki67 and PCNA were tightly associated. This contrasted with class III tumors which displayed two separate clusters (EGFR, RB, pAKT and CND1), and (ERK2, p16 and p14). Conclusion We demonstrated that HNSCC classified by a combination of HPV DNA presence and p16 expression status have distinct molecular phenotypes. Class III tumors, distinct from HPV+ but p16-negative class II tumors, have a unique molecular clustering profile, lending support to the proposed 3-class model. Significance These findings may have significant implications in patient selection for HPV-specific therapies. Support AAO/HNSF Resident Research Grant 26357 (PMW).

Oropharyngeal squamous cell cancers (OSCC) bearing transcriptionally active human papillomavirus (HPV) display distinct protein expression profile

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10028-10028 ◽  
Author(s):  
P. Weinberger ◽  
P. Kountourakis ◽  
C. Sasaki ◽  
B. Haffty ◽  
R. Camp ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Expression ◽  
Expression Profiles ◽  
Growth Factor Receptor ◽  
Class Ii ◽  
Class I ◽  
Class Iii ◽  
Ki 67 ◽  
Hpv Dna ◽  
P16 Expression

10028 Background: It is known that among HPV DNA+ OSCCs only the transcriptionally active ones are biologically and clinically relevant. pRb downregulation by HPVE7 results in p16 upregulation. We previously showed (JCO, Feb 2006) that p16 expression defines transcriptionally active HPV+ tumors. Thus, OSCC tumors can be Class I: HPV−/p16−, Class II: HPV+/p16−, or Class III: HPV+/p16+. We hypothesized that tumors classified by these criteria would show different protein expression profiles. Methods: Following institutional review board approval, paraffin-embedded specimens from 77 patients were collected from Yale-New Haven Hospital archives. Patients with OSCC treated with radiotherapy (RT) or surgery and RT were eligible. We used real-time polymerase chain reaction for HPV 16 and immunohistochemistry for p16 protein expression to classify 77 patients with OSCC. Tumors were classified into a 3-class model based on p16 expression and HPV DNA presence: Class I (HPV−, p16−) Class II (HPV+, p16−) and Class III (HPV+, p16+). A tissue microarray including these cases was constructed and examined for 13 target proteins with known involvement in tumor suppression or progression. We used a method of in-situ automated quantitative protein expression analysis (AQUA). Protein signal (AQUA score) was scored on a scale of 0–255.Protein expression between groups was analyzed by analysis of variance (ANOVA). Results: Thirty tumors were class I (39%), 29 were class II (38%), and 18 were class III (23%). There were significant differences for protein expression of Met (p=0.005), β-catenin (p=0.009), pRb (p=0.001), p53(p=0.026), epidermal growth factor receptor (EGFR) (p=0.009) and Vascular Endothelial Growth Factor (VEGF) (p=0.028). There was no difference for ki-67, COX2, p27, p21 or Cyclin D1 expression, while ERK2 and p14 trended towards significance (p=0.09 and 0.054, respectively). Conclusions: We demonstrated that tumors classified by HPV DNA presence and p16 expression status have different molecular phenotypes. Of particular note, class III tumors demonstrated increased expression of Met, β-catenin, EGFR and VEGF. These findings may prove useful for patient selection for molecular-targeted therapies. [Table: see text]

scholarly journals Environmental Cadmium Exposure and Dental Indices in Orthodontic Patients

Healthcare ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 413
Author(s):  
Hui-Ling Chen ◽  
Jason Chen-Chieh Fang ◽  
Chia-Jung Chang ◽  
Ti-Feng Wu ◽  
I-Kuan Wang ◽  
...  
Keyword(s):  
Cadmium Concentration ◽  
Class Ii ◽  
Cadmium Exposure ◽  
Class I ◽  
P Value ◽  
Tooth Decay ◽  
Class Iii ◽  
Orthodontic Patients ◽  
Urine Cadmium ◽  
The Mean

Background. Previous studies have shown that environmental cadmium exposure could disrupt salivary gland function and is associated with dental caries and reduced bone density. Therefore, this cross-sectional study attempted to determine whether tooth decay with tooth loss following cadmium exposure is associated with some dental or skeletal traits such as malocclusions, sagittal skeletal pattern, and tooth decay. Methods. Between August 2019 and June 2020, 60 orthodontic patients with no history of previous orthodontics, functional appliances, or surgical treatment were examined. The patients were stratified into two groups according to their urine cadmium concentrations: high (>1.06 µg/g creatinine, n = 28) or low (<1.06 µg/g creatinine, n = 32). Results. The patients were 25.07 ± 4.33 years old, and most were female (female/male: 51/9 or 85%). The skeletal relationship was mainly Class I (48.3%), followed by Class II (35.0%) and Class III (16.7%). Class I molar relationships were found in 46.7% of these patients, Class II molar relationships were found in 15%, and Class III molar relationships were found in 38.3%. The mean decayed, missing, and filled surface (DMFS) score was 8.05 ± 5.54, including 2.03 ± 3.11 for the decayed index, 0.58 ± 1.17 for the missing index, and 5.52 ± 3.92 for the filled index. The mean index of complexity outcome and need (ICON) score was 53.35 ± 9.01. The facial patterns of these patients were within the average low margin (26.65 ± 5.53 for Frankfort–mandibular plane angle (FMA)). There were no significant differences in the above-mentioned dental indices between patients with high urine cadmium concentrations and those with low urine cadmium concentrations. Patients were further stratified into low (<27, n = 34), average (27–34, n = 23), and high (>34, n = 3) FMA groups. There were no statistically significant differences in the urine cadmium concentration among the three groups. Nevertheless, a marginally significant p-value of 0.05 for urine cadmium concentration was noted between patients with low FMA and patients with high FMA. Conclusion. This analysis found no association between environmental cadmium exposure and dental indices in our orthodontic patients.

scholarly journals The visual categorization of production automotive seats on descriptors of comfort

Work ◽  
2021 ◽  
Vol 68 (s1) ◽  
pp. S69-S85
Author(s):  
Tugra Erol ◽  
Cyriel Diels ◽  
James Shippen ◽  
Dale Richards
Keyword(s):  
Hierarchical Clustering ◽  
Clustering Analysis ◽  
The Other ◽  
Visual Design ◽  
Hierarchical Clustering Analysis ◽  
Card Sorting ◽  
Design Attributes ◽  
Comfort Perception ◽  
Automotive Production

BACKGROUND: The role of appearance of automotive seats on perceived comfort and comfort expectancy has been acknowledged in previous research but it has not been investigated in depth. OBJECTIVE: To identify the effects of the appearance of production automotive seats, based on the hypothesis that visual design differentiations are affective in creating comfort expectations. The significance of the descriptors Sporty, Luxurious and Comfortable and the associated visual design attributes was of interest. METHOD: Images from 38 automotive production seats were used in an image-based card sorting app (qCard) with a total of 24 participants. Participants were asked to categorize the different seat designs varying from 1: least, to 9: most for all three descriptors.The resulting data was analyzed using hierarchical clustering analysis. RESULTS: The results indicated that the perceived Sporty, Luxurious and Comfortable were descriptor items that significantly differentiated seats with certain design attributes. It was found that for the Sporty perception the integrated headrest design and angular shapes were key. On the other hand, the Comfort perception was characterised by seating with a separate headrest and rounded seat back/cushion shapes. CONCLUSIONS: For seat design processes, the method enables a practical way to identify elements conveying Sporty, Comfortable and Luxurious perception.

scholarly journals A convenient method of preparation of high-activity urease from Canavalia ensiformis by covalent chromatography and an investigation of its thiol groups with 2,2'-dipyridyl disulphide as a thiol titrant and reactivity probe

1976 ◽  
Vol 159 (2) ◽  
pp. 245-257 ◽  
Author(s):  
R Norris ◽  
K Brocklehurst
Keyword(s):  
Convenient Method ◽  
Specific Activity ◽  
Class Ii ◽  
High Reactivity ◽  
Class I ◽  
Thiol Groups ◽  
Class Iii ◽  
Active Centre ◽  
Class Ib ◽  
Covalent Chromatography

1. A convenient method of preparation of jack-bean urease (EC3.5.1.5) involving covalent chromatography by thiol-disulphide interchange is described. 2. Urease thus prepared has specific activity comparable with the highest value yet reported (44.5 ± 1.47 kat/kg, Km = 3.32 ± 0.05 mM; kcat. = 2.15 × 104 ± 0.05 × 104s-1 at pH7.0 and 38°C). 3. Titration of the urease thiol groups with 2,2'-dipyridyl disulphide (2-Py-S-S-2-Py) and application of the method of Tsou Chen-Lu [(1962) Sci. Sin.11, 1535-1558] suggests that the urease molecule (assumed to have mol.wt. 483000 and ε280 = 2.84 × 105 litre·mol-1-cm-1) contains 24 inessential thiol groups of relatively high reactivity (class-I), six ‘essential’ thiol groups of low reactivity (class-II) and 54 buried thiol groups (class-III) which are exposed in 6M-guanidinium chloride. 4. The reaction of the class-I thiol groups with 2-Py-S-S-2-Py was studied in the pH range 6-11 at 25°C(I = 0.1 mol/l) by stopped-flow spectrophotometry, and the analogous reaction of the class-II thiol groups by conventional spectrophotometry. 5. The class-I thiol groups consist of at least two sub-classes whose reactions with 2-Py-S-S-2-Py are characterized by (a) pKa = 9.1, k = 1.56 × 104M-1·s-1 and (b) pKa = 8.1, k = 8.05 × 102M-1·s-1 respectively. The reaction of the class-II thiol groups is characterized by pKa = 9.15 and k = 1.60 × 102M-1·s-1. 6. At pH values 7-8 the class-I thiol groups consist of approx. 50% class-Ia groups and 50% class-Ib groups. The ratio class Ia/class Ib decreases as the pH is raised according to a pKa value ≥ approx. 9.5, and at high pH the class-I thiol groups consist of at most 25% class-Ia groups and at least 75% class-Ib groups. 7. The reactivity of the class-II thiol groups towards 2-Py-S-S-2-Py is insensitive to the nature of the group used to block the class-I thiols. 8. All the ‘essential’ thiol groups in urease appear to be eeactive only as uncomplicated thiolate ions. The implications of this for the active-centre chemistry of urease relative to that of the thiol proteinases are discussed.

Regulation of mouse CYP1A1 gene expression by dioxin: requirement of two cis-acting elements during induction

1989 ◽  
Vol 9 (6) ◽  
pp. 2378-2386
Author(s):  
L A Neuhold ◽  
Y Shirayoshi ◽  
K Ozato ◽  
J E Jones ◽  
D W Nebert
Keyword(s):  
Gene Expression ◽  
Simian Virus 40 ◽  
Class Ii ◽  
Simian Virus ◽  
Class I ◽  
Ah Receptor ◽  
Class Iii ◽  
Cis Acting ◽  
Cyp1a1 Gene ◽  
Sv40 Dna

The mouse cytochrome P1450 (CYP1A1) gene is responsible for the metabolism of numerous carcinogens and toxic chemicals. Induction by the environmental contaminant tetrachlorodibenzo-p-dioxin (TCDD) requires a functional aromatic hydrocarbon (Ah) receptor. We examined the 5'-flanking region of the CYP1A1 gene in mouse hepatoma Hepa-1 wild-type cells and a mutant line having a defect in chromatin binding of the TCDD-receptor complex. We identified two cis-acting elements (distal, -1071 to -901 region; proximal, -245 to -50 region) required for constitutive and TCDD-inducible CYP1A1 gene expression. Three classes of DNA-protein complexes binding to the distal element were identified: class I, found only in the presence of TCDD and a functional Ah receptor, that was heat labile and not competed against by simian virus 40 (SV40) early promoter DNA; class II, consisting of at least three constitutive complexes that were heat stable and bound to SV40 DNA; and class III, composed of at least three constitutive complexes that were thermolabile and were not competed against by SV40 DNA. Essential contacts for these proteins were centered at -993 to -990 for the class I complex, -987, -986, or both for the class II complexes, and -938 to -927 for the class III complexes. The proximal element was absolutely essential for both constitutive and TCDD-inducible CYP1A1 gene expression, and at least two constitutive complexes bound to this region. These data are consistent with the proximal element that binds proteins being necessary but not sufficient for inducible gene expression; interaction of these proteins with those at the distal element was found to be required for full CYP1A1 induction by TCDD.

Prevalence of Malocclusions in Autistic Patients in Isfahan

2021 ◽  
Author(s):  
Zahra Ali Mehtari ◽  
Mehdi Rafiei ◽  
Saeed Azarbayjani ◽  
Neda Ahmadi Rouzbehani ◽  
Amir Hossain Moeini
Keyword(s):  
Class Ii ◽  
Autism Spectrum ◽  
Open Bite ◽  
Class I ◽  
Dental Student ◽  
Class Iii ◽  
Cross Sectional ◽  
Deep Bite ◽  
Normal Occlusion ◽  
Age Range

Introduction: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders diagnosed by impairments in social interaction and communication with repetitive and restrictive stereotyped behavioral patterns. The Prevalence of autism has been reported to be increased in recent years. This study aimed to assess the prevalence of different types of malocclusion among ASD patients in Isfahan in 2018. Materials & Methods: In a descriptive and cross-sectional trial, 92 ASD patients were studied in the age range of 7-18 years at the center for autism patients in Isfahan. Clinical oral examinations of patients are taken to assess the involved malocclusions (Cl I, Cl II and Cl III malocclusions) and malocclusion traits (deep bite, open bite and cross bite) by an educated dental student under the supervision of an orthodontist under natural light. The data are reported using frequency and percentage indices. Results: Class I malocclusion had the highest prevalence 54.3% (50) among ASD patients and the prevalence of class II and class III were found to be 19.6% (18) and 7.6% (7) respectively. The frequency of malocclusions traits of deep bite, cross bite and the open bite were 27.2% (25), 18.5% (17) and 7.6% (7) respectively. Among of the total patients, 65.2% (60) showed normal bite and 18/5% (17) showed Normal occlusion. Conclusion: ASD patients showed class I, class II and class III malocclusions from the most to least frequency and the most frequent malocclusion traits were also deep bite, cross bite and open bite respectively.

Prevalence of Malocclusion among School Children of Biratnagar, Nepal

2021 ◽  
Vol 11 (1) ◽  
pp. 46-48
Author(s):  
Nidhi Giri ◽  
Anand Acharya ◽  
Kanika Yadav
Keyword(s):  
School Children ◽  
Class Ii ◽  
Cross Sectional Study ◽  
Class I ◽  
Class Iii ◽  
Cross Sectional ◽  
Total Study Population ◽  
Medical College ◽  
Normal Occlusion ◽  
Study Population

Introduction: Various forms of malocclusion are a matter of serious concern in Nepalese population. This study was carried out to understand the prevalence of malocclusion among the school children of Biratnagar. The objective of this research is to find out the prevalence of malocclusion of children from different schools of Biratnagar visiting the Pedodontics and Orthodontics department of Nobel Medical College and Teaching Hospital, Biratnagar. Materials and Method: A descriptive cross sectional study method was used in this research. Data was collected by using direct observation of the subjects and occlusal assessment was done according to Angle’s classification and Dewey’s modification types of class I, class II and class III malocclusion. Result: Subjects with normal occlusion was found to be 39 % and with malocclusion was found to be 61%. Among them, class I malocclusion (60%) and angles class II div I subjects (88.33%) were in majority of the total study population. Conclusion: The present study helps to determine the prevalence of malocclusion and need of orthodontic treatment for the school children of Biratnagar

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