The anti-PD1 monoclonal antibody pembrolizumab improves survival in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Patients with locoregional, pathologically high-risk HNSCC recur frequently despite adjuvant... more
The anti-PD1 monoclonal antibody pembrolizumab improves survival in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Patients with locoregional, pathologically high-risk HNSCC recur frequently despite adjuvant cisplatin–radiation therapy (CRT). Targeting PD1 may reverse immunosuppression induced by HNSCC and CRT. We conducted a phase I trial with an expansion cohort (n = 20) to determine the recommended phase II schedule (RP2S) for adding fixed-dose pembrolizumab to standard adjuvant CRT. Eligible patients had resected HPV-negative, stage III–IV oral cavity, pharynx, or larynx HNSCC with extracapsular nodal extension or positive margin. RP2S was declared if three or fewer dose-limiting toxicities (DLT) occurred in a cohort of 12. DLT was defined as grade 3 or higher non-hematologic adverse event (AE) related to pembrolizumab, immune-related AE requiring over 2 weeks of systemic steroids, or unacceptable RT delay. A total of 34 patients enrolled at 23 NRG instituti...
Research Interests:
Secretory carcinomas of the breast are rare tumors with distinct histologic features, recurrent t(12;15)(p13;q25) translocation resulting in ETV6-NTRK3 gene fusion and indolent clinical behavior. Mammary analog secretory carcinomas... more
Secretory carcinomas of the breast are rare tumors with distinct histologic features, recurrent t(12;15)(p13;q25) translocation resulting in ETV6-NTRK3 gene fusion and indolent clinical behavior. Mammary analog secretory carcinomas arising in other sites are histopathologically similar to the breast tumors and also harbor ETV6-NTRK3 fusions. Breast secretory carcinomas are often triple (estrogen and progesterone receptor, HER2) negative with a basal-like immunophenotype. However, genomic studies are lacking, and whether these tumors share genetic features with other basal and/or triple negative breast cancers is unknown. Aside from shared ETV6-NTRK3 fusions, the genetic relatedness of secretory carcinomas arising in different sites is also uncertain. We immunoprofiled and sequenced 510 cancer-related genes in nine breast secretory carcinomas and six salivary gland mammary analog secretory carcinomas. Immunoprofiles of breast and salivary gland secretory carcinomas were similar. All ...
Research Interests: Pathology, Breast Cancer, Biology, Adolescent, Medicine, and 15 moreHumans, Female, Male, Aged, Middle Aged, Adult, Mammary gland, Breast carcinoma, Salivary Gland, Gene expression profiling, Breast Neoplasms, Salivary gland neoplasms, Medical and Health Sciences, Modern Pathology, and Mammary analogue secretory carcinoma
Purpose: We previously demonstrated an association between decreased SMAD4 expression and cetuximab resistance in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to further elucidate the clinical relevance of... more
Purpose: We previously demonstrated an association between decreased SMAD4 expression and cetuximab resistance in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to further elucidate the clinical relevance of SMAD4 loss in HNSCC. Experimental Design: SMAD4 expression was assessed by immunohistochemistry in 130 newly diagnosed and 43 recurrent HNSCC patients. Correlative statistical analysis with clinicopathological data was also performed. OncoFinder, a bioinformatics tool, was used to analyze molecular signaling in TCGA tumors with low or high SMAD4 mRNA levels. The role of SMAD4 was investigated by shRNA knockdown and gene reconstitution of HPV-negative HNSCC cell lines in vitro and in vivoResults: Our analysis revealed that SMAD4 loss was associated with an aggressive, HPV-negative, cetuximab-resistant phenotype. We found a signature of pro-survival and anti-apoptotic pathways that were commonly dysregulated in SMAD4-low cases derived from TCGA-HNSCC ...
Research Interests:
Human papillomavirus (HPV) 16 plays an etiologic role in a growing subset of HNSCCs, where viral expression of the E6 and E7 oncoproteins are necessary for tumor growth and maintenance. Although patients with HPV(+) tumors have a more... more
Human papillomavirus (HPV) 16 plays an etiologic role in a growing subset of HNSCCs, where viral expression of the E6 and E7 oncoproteins are necessary for tumor growth and maintenance. Although patients with HPV(+) tumors have a more favorable prognosis, there are currently no HPV-selective therapies. Recent studies identified differential receptor tyrosine kinase (RTK) profiles in HPV(+) vs. HPV(-) tumors. One such RTK, HER3, is overexpressed and interacts with phosphoinositide 3-kinase (PI3K) in HPV(+) tumors. Therefore, we investigated the role of HPV oncoproteins in regulating HER3-mediated signaling, and determined whether HER3 could be a molecular target in HPV(+) HNSCCs. HER3 was investigated as a molecular target in HPV(+) HNSCC using established cell lines, patient-derived xenografts (PDX), and human tumor specimens. A mechanistic link between HPV and HER3 was examined by augmenting E6 and E7 expression levels in HNSCC cell lines. The dependency of HPV(+) and HPV(-) HNSCC ...
Research Interests:
Mitochondrial DNA (mtDNA) mutations scattered through coding and noncoding regions have been reported in cancer. The mechanisms that generate such mutations and the importance of mtDNA mutations in tumor development are still not clear.... more
Mitochondrial DNA (mtDNA) mutations scattered through coding and noncoding regions have been reported in cancer. The mechanisms that generate such mutations and the importance of mtDNA mutations in tumor development are still not clear. Here we present the identification of a specific and highly polymorphic homopolymeric C stretch (D310), located within the displacement (D) loop, as a mutational hotspot in primary tumors. Twenty-two % of the 247 primary tumors analyzed harbored somatic deletions/insertions at this mononucleotide repeat. Moreover, these alterations were also present in head and neck preneoplastic lesions. We further characterized the D310 variants that appeared in the lung and head and neck tumors. Most of the somatic alterations found in tumors showed deletion/insertions of 1- or 2-bp generating D310 variants identical to constitutive polymorphisms described previously. Sequencing analysis of individual clones from lymphocytes revealed that patients with D310 mutati...
Research Interests:
Although p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infection, is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC), its prevalence and significance have not been... more
Although p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infection, is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC), its prevalence and significance have not been well established in cancer of the oral cavity, hypopharynx, or larynx, collectively referred as non-OPSCC, where HPV infection is less common than in the oropharynx. p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129, 0234, and 0522 studies were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). Hazard ratios from Cox models were expressed as positive or negative, stratified by trial, and adjusted for clinical characteristics. p16 expression was positive in 14.1% (12 of 85), 24.2% (23 of 95), and 19.0% (27 of 142) and HPV ISH was positive in 6.5% (six of 93), 14.6% (15 of 103), and 6.9% (seven of 101) of non-OPSCCs from RTOG 0129, 0234, and 0522 studies, respectively. Hazard ratios for p16 expression were 0.63 ...
Research Interests: Oncology, Immunohistochemistry, Treatment Outcome, Medicine, HUMAN PAPILLOMAVIRUS, and 13 moreHumans, Smoking, Head and Neck Cancer, Clinical oncology, Head and neck squamous cell carcinoma, Cisplatin, Oral Squamous Cell Carcinoma (OSCC), Prognosis, Larynx, Disease Free Survival, Papillomaviridae, Papillomavirus Infections, and Head and neck neoplasms
Oral squamous cell carcinoma has a low five-year survival rate, which may be due to late detection and a lack of effective tumor-specific therapies. Using a high throughput drug discovery strategy termed one-bead one-compound... more
Oral squamous cell carcinoma has a low five-year survival rate, which may be due to late detection and a lack of effective tumor-specific therapies. Using a high throughput drug discovery strategy termed one-bead one-compound combinatorial library, the authors identified six compounds with high binding affinity to different human oral squamous cell carcinoma cell lines but not to normal cells. Current work is under way to develop these ligands to oral squamous cell carcinoma specific imaging probes or therapeutic agents.
Research Interests:
We tested the efficacy and toxicity of cisplatin plus accelerated fractionation with a concomitant boost (AFX-C) versus standard fractionation (SFX) in locally advanced head and neck carcinoma (LA-HNC). Patients had stage III to IV... more
We tested the efficacy and toxicity of cisplatin plus accelerated fractionation with a concomitant boost (AFX-C) versus standard fractionation (SFX) in locally advanced head and neck carcinoma (LA-HNC). Patients had stage III to IV carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Radiation therapy schedules were 70 Gy in 35 fractions over 7 weeks (SFX) or 72 Gy in 42 fractions over 6 weeks (AFX-C). Cisplatin doses were 100 mg/m(2) once every 3 weeks for two (AFX-C) or three (SFX) cycles. Toxicities were scored by using National Cancer Institute Common Toxicity Criteria 2.0 and the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. Overall survival (OS) and progression-free survival (PFS) rates were estimated by using the Kaplan-Meier method and were compared by using the one-sided log-rank test. Locoregional failure (LRF) and distant metastasis (DM) rates were estimated by using the cumulative incidence method and G...
Research Interests: Radiation Therapy, Medicine, Humans, Internal Medicine, Head and Neck Cancer, and 15 moreFemale, Male, Clinical oncology, Cisplatin, Aged, Middle Aged, Carcinoma, Adult, Disease Progression, Risk Factors, Chemoradiotherapy, Antineoplastic Agents, Disease Free Survival, Neoplasm staging, and Head and neck neoplasms
Purpose To report results of a randomized phase II trial (Radiation Therapy Oncology Group RTOG-0234) examining concurrent chemoradiotherapy and cetuximab in the postoperative treatment of patients with squamous cell carcinoma of the head... more
Purpose To report results of a randomized phase II trial (Radiation Therapy Oncology Group RTOG-0234) examining concurrent chemoradiotherapy and cetuximab in the postoperative treatment of patients with squamous cell carcinoma of the head and neck (SCCHN) with high-risk pathologic features. Patients and Methods Eligibility required pathologic stage III to IV SCCHN with gross total resection showing positive margins and/or extracapsular nodal extension and/or two or more nodal metastases. Patients were randomly assigned to 60 Gy radiation with cetuximab once per week plus either cisplatin 30 mg/m2 or docetaxel 15 mg/m2 once per week. Results Between April 2004 and December 2006, 238 patients were enrolled. With a median follow-up of 4.4 years, 2-year overall survival (OS) was 69% for the cisplatin arm and 79% for the docetaxel arm; 2-year disease-free survival (DFS) was 57% and 66%, respectively. Patients with p16-positive oropharynx tumors showed markedly improved survival outcome r...
Research Interests: Oncology, Radiation Therapy, Medicine, Humans, Internal Medicine, and 15 moreHead and Neck Cancer, Female, Male, Clinical oncology, Head and neck squamous cell carcinoma, Cisplatin, Aged, Middle Aged, Adult, Chemoradiotherapy, Cetuximab, Postoperative care, Disease Free Survival, Neoplasm staging, and Head and neck neoplasms
Skp2 is a member of the F-box family of substrate-recognition subunits of SCF ubiquitin–protein ligase complexes that has been implicated in the ubiquitin-mediated degradation of several key regulators of mammalian G 1 progression,... more
Skp2 is a member of the F-box family of substrate-recognition subunits of SCF ubiquitin–protein ligase complexes that has been implicated in the ubiquitin-mediated degradation of several key regulators of mammalian G 1 progression, including the cyclin-dependent kinase inhibitor p27, a dosage-dependent tumor suppressor protein. In this study, we examined Skp2 and p27 protein expression by immunohistochemistry in normal oral epithelium and in different stages of malignant oral cancer progression, including dysplasia and oral squamous cell carcinoma. We found that increased levels of Skp2 protein are associated with reduced p27 in a subset of oral epithelial dysplasias and carcinomas compared with normal epithelial controls. Tumors with high Skp2 (>20% positive cells) expression invariably showed reduced or absent p27 and tumors with high p27 (>20% positive cells) expression rarely showed Skp2 positivity. Increased Skp2 protein levels were not always correlated with increased ce...
Research Interests:
We report 52 cases of a unique and pathologically distinctive form of inflammatory gingival hyperplasia in young patients. Clinically, the average age of patients in this study was 11.8 years, with a 2.3:1 female predominance. Caucasians... more
We report 52 cases of a unique and pathologically distinctive form of inflammatory gingival hyperplasia in young patients. Clinically, the average age of patients in this study was 11.8 years, with a 2.3:1 female predominance. Caucasians comprised 77% of the cases, and nearly all of the lesions were located on the anterior gingiva, with 81% affecting maxillary gingiva. The most classic clinical presentation was a papillary, often pedunculated, red and easily bleeding gingival overgrowth in young patients. Histopathologically, the lesions exhibited a subtle papillary epithelial hyperplasia with prominent intercellular edema and neutrophilic exocytosis of the hyperplastic surface squamous epithelium. Based on the characteristic clinical and histologic features, we conclude that this lesion is a distinct subtype of gingival hyperplasia. Although previously described as juvenile spongiotic gingivitis, we propose the term localized juvenile spongiotic gingival hyperplasia as a more accurate designation.
Research Interests: Pathology, Dentistry, Adolescent, Medicine, Humans, and 8 moreChild, Female, Male, Hyperplasia, Adult, Lesion, Gingivitis, and gingival hyperplasia
Research Interests: Genetics, Pathology, Biology, Immunohistochemistry, Medicine, and 15 moreGene expression, Quantitative PCR, Humans, Polymerase Chain Reaction, Real Time, Epidermal Growth Factor Receptor, Mouth Neoplasms, Protein Expression, Oral Squamous Cell Carcinoma, Large Scale, Formaldehyde, Matrix Metalloproteinase, real time polymerase chain reaction, Medical and Health Sciences, and Modern Pathology
Research Interests: Biology, Cell Biology, Transcription Factors, Medicine, Gene expression, and 15 moreCell Culture, Humans, Clock, Keratinocytes, Low Dose, Ultraviolet, Circadian Rhythm, Clinical Sciences, mRna expression levels, PER, INVESTIGATIVE, Cell Cycle Proteins, Circadian Clock, Signaling pathway, and Ultraviolet Rays
Purpose Glioma-associated oncogene family zinc finger 1 (GLI1) expression was assessed to determine a potential role of hedgehog (Hh) signaling in head and neck squamous cell carcinoma (HNSCC). Additional proteins known to be modulated by... more
Purpose Glioma-associated oncogene family zinc finger 1 (GLI1) expression was assessed to determine a potential role of hedgehog (Hh) signaling in head and neck squamous cell carcinoma (HNSCC). Additional proteins known to be modulated by Hh signaling, including beta-catenin (CTNNB1) and epidermal growth factor receptor (EGFR), were also assessed to determine the correlation among these distinct signaling pathways. Patients and Methods Nuclear GLI1 and CTNNB1 expression levels were determined in tumors from patients enrolled on Radiation Therapy Oncology Group (RTOG) 9003, a radiation fractionation trial. The results were also correlated with previously determined EGFR expression. The expression levels were evaluated in relation to three end points: time to metastasis (TTM), time to disease progression (TDP), and overall survival (OS). Results Among 1,068 eligible patients, data on GLI1, CTNNB1, and EGFR were available in 339, 164, and 300 patients, respectively. Although CTNNB1 exp...
Research Interests: Oncology, Radiation Therapy, Immunohistochemistry, Cancer Research, Medicine, and 15 moreCanada, Humans, Female, Oncogene, Male, Clinical oncology, Head and neck squamous cell carcinoma, Aged, Middle Aged, Epidermal Growth Factor Receptor, Disease Progression, Risk Assessment, Proportional Hazards Models, Neoplasm staging, and Head and neck neoplasms
Purpose Tobacco smoking is associated with oropharynx cancer survival, but to what extent cancer progression or death increases with increasing tobacco exposure is unknown. Patients and Methods Patients with oropharynx cancer enrolled... more
Purpose Tobacco smoking is associated with oropharynx cancer survival, but to what extent cancer progression or death increases with increasing tobacco exposure is unknown. Patients and Methods Patients with oropharynx cancer enrolled onto a phase III trial of radiotherapy from 1991 to 1997 (Radiation Therapy Oncology Group [RTOG] 9003) or of chemoradiotherapy from 2002 to 2005 (RTOG 0129) were evaluated for tumor human papillomavirus status by a surrogate, p16 immunohistochemistry, and for tobacco exposure by a standardized questionnaire. Associations between tobacco exposure and overall survival (OS) and progression-free survival (PFS) were estimated by Cox proportional hazards models. Results Prevalence of p16-positive cancer was 39.5% among patients in RTOG 9003 and 68.0% in RTOG 0129. Median pack-years of tobacco smoking were lower among p16-positive than p16-negative patients in both trials (RTOG 9003: 29 v 45.9 pack-years; P = .02; RTOG 0129: 10 v 40 pack-years; P < .001)....
Research Interests:
Research Interests: Oncology, Clinical Trial, Radiation Therapy, Immunohistochemistry, Medicine, and 15 moreHumans, Internal Medicine, Female, Male, Head and neck squamous cell carcinoma, Clinical Sciences, Aged, Middle Aged, Epidermal Growth Factor Receptor, Molecular Marker, Overall Survival, Proportional Hazards Models, Microvessels, Disease Free Survival, and Head and neck neoplasms
Research Interests: Education, Dermatology, Medicine, HUMAN PAPILLOMAVIRUS, Humans, and 15 moreInfectious Disease, Female, Male, Aged, Middle Aged, Carcinoma, Adult, New England, Prognosis, Proportional Hazards Models, Psychology and Cognitive Sciences, Medical Cell Biology, Papillomavirus Infections, Alphapapillomavirus, and Medical and Health Sciences
Research Interests:
Research Interests: Biology, Medicine, Western blotting, In Situ Hybridization, Phylogeny, and 15 moreCell line, Brain, Humans, Mice, Animals, Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis, Fibroblast Growth Factor, Amino Acid Sequence, Recombinant Proteins, Biochemistry and cell biology, Quantitative polymerase chain reaction, Molecular Sequence Data, Tissue distribution, Medical biochemistry and metabolomics, and Fibroblast growth factors
Research Interests:
Research Interests:
Research Interests: Pathology, Treatment Outcome, Medicine, Biopsy, Acute Myeloid Leukemia, and 15 moreHumans, Fluorescence in situ hybridization, Male, American, Bone marrow, Neutrophils, Gingiva, Adult, Immunophenotyping, Antineoplastic Agents, Bone Marrow Cells, Sweet Syndrome, Chromosome deletion, Myelodysplastic syndromes, and Medical and Health Sciences
The CDKN2A gene locus encodes two different proteins derived from alternative splicing. p16 (exons 1alpha, 2, and 3) acts as a G1 cell cycle regulator, and p14ARF (exons 1beta, 2, and 3) acts to modulate MDM2-mediated degradation of p53.... more
The CDKN2A gene locus encodes two different proteins derived from alternative splicing. p16 (exons 1alpha, 2, and 3) acts as a G1 cell cycle regulator, and p14ARF (exons 1beta, 2, and 3) acts to modulate MDM2-mediated degradation of p53. Inactivation of p16 is a common finding in many cancers; however, there is little data on CDKN2A gene abnormalities in oral precancer. In this longitudinal study, we examined changes in the CDKN2A gene locus in sequential epithelial dysplasias and oral carcinomas from 11 patients. Genomic DNA was extracted from laser-microdissected lesional tissue, and exons 1alpha, 1beta, and 2 were analyzed by duplex PCR. Immunohistochemistry was done to identify p16 and p14ARF protein expression. Two adjacent polymorphic microsatellite markers were used for allelotyping. Homozygous deletion of exon 1alpha was identified in 2 of 17 (12%) precancerous lesions. Loss of either exon 1alpha, exon 2, or both was seen in seven of nine (78%) carcinomas. In five of these c...
Research Interests: Genetics, Cancer, Biology, Cell Cycle, Immunohistochemistry, and 15 moreCancer Research, Linear Model, Humans, Female, Alternative splicing, Longitudinal Studies, Genomic DNA, Epithelial cells, Longitudinal Study, Cell Cycle regulation, Disease Progression, Alternative Splicing, Exon, gene amplification, and Carcinoma in situ
The CDKN2A gene locus encodes two different proteins derived from alternative splicing. p16 (exons 1alpha, 2, and 3) acts as a G1 cell cycle regulator, and p14ARF (exons 1beta, 2, and 3) acts to modulate MDM2-mediated degradation of p53.... more
The CDKN2A gene locus encodes two different proteins derived from alternative splicing. p16 (exons 1alpha, 2, and 3) acts as a G1 cell cycle regulator, and p14ARF (exons 1beta, 2, and 3) acts to modulate MDM2-mediated degradation of p53. Inactivation of p16 is a common finding in many cancers; however, there is little data on CDKN2A gene abnormalities in oral precancer. In this longitudinal study, we examined changes in the CDKN2A gene locus in sequential epithelial dysplasias and oral carcinomas from 11 patients. Genomic DNA was extracted from laser-microdissected lesional tissue, and exons 1alpha, 1beta, and 2 were analyzed by duplex PCR. Immunohistochemistry was done to identify p16 and p14ARF protein expression. Two adjacent polymorphic microsatellite markers were used for allelotyping. Homozygous deletion of exon 1alpha was identified in 2 of 17 (12%) precancerous lesions. Loss of either exon 1alpha, exon 2, or both was seen in seven of nine (78%) carcinomas. In five of these c...
Research Interests: Genetics, Cancer, Biology, Cell Cycle, Immunohistochemistry, and 15 moreCancer Research, Linear Model, Humans, Female, Alternative splicing, Longitudinal Studies, Genomic DNA, Epithelial cells, Longitudinal Study, Cell Cycle regulation, Disease Progression, Alternative Splicing, Exon, gene amplification, and Carcinoma in situ
Research Interests:
Oral health care professionals could drastically improve the quality of life for patients with potentially malignant oral lesions by using a noninvasive test that could be used to detect cancer using saliva. Promoter DNA hypermethylation... more
Oral health care professionals could drastically improve the quality of life for patients with potentially malignant oral lesions by using a noninvasive test that could be used to detect cancer using saliva. Promoter DNA hypermethylation is a critical step in oral carcinogenesis and has a number of significant advantages over genetic and protein diagnostic markers. Methylight is a recently developed assay that rapidly quantifies promoter hypermethylation and could potentially be applied into a clinical setting.
Research Interests:
Although an important risk factor for oral cancer is the presence of epithelial dysplasia, most of these lesions will not progress to malignancy. Presently, for the individual patient with dysplasia, there are few reliable markers that... more
Although an important risk factor for oral cancer is the presence of epithelial dysplasia, most of these lesions will not progress to malignancy. Presently, for the individual patient with dysplasia, there are few reliable markers that may indicate the likelihood of progression to oral cancer. Cathepsin L is a lysosomal protease that degrades extracellular matrix material. Because cathepsin L is frequently overexpressed in oral squamous cell carcinoma (SCC) we hypothesized that it is also overexpressed in oral premalignancy and that premalignant lesions that progressed to oral cancer expressed higher levels of cathepsin L than those premalignant lesions that did not. In this retrospective pilot study we examined changes in cathepsin L expression at the mRNA level using quantitative TaqMan RT-PCR and at the protein level by immunohistochemistry in 33 routinely processed oral dysplastic lesions and 14 SCCs obtained from 33 patients. Sixteen of the dysplastic lesions progressed to oral SCC and 17 did not after several years of follow-up. Cathepsin L mRNA was overexpressed in 16/33 (48%) dysplastic lesions and in 9/14 (64%) oral SCC. Cathepsin L protein was also overexpressed in a large proportion of dysplasias and cancers. Overexpression was independent of dysplasia grade and identified in both those patients who progressed to oral SCC and in those who did not. Levels of cathepsin L mRNA and protein did not differ significantly in the progressing versus non-progressing dysplasias (P=0.27). However, cathepsin L mRNA and protein were significantly lower in the non-progressing dysplasias when compared to the oral cancers (P=0.03) but not in the progressing dysplasias suggesting a trend for dysplasias with overexpressed cathepsin L to be more likely to progress to oral cancer.
Research Interests:
Research Interests:
Research Interests:
Research Interests: Animal Behavior, Pain, Immunohistochemistry, Medicine, Humans, and 15 moreMice, Animals, Morphine, Clinical Sciences, European, Fluorescent Antibody Technique, Neoplasms, Soft Tissue, Culture Media, Neurosciences, Pain Measurement, Enzyme Linked Immunosorbent Assay, Pain Threshold, reverse transcriptase polymerase chain reaction, and Pharmacology and pharmaceutical sciences
Research Interests:
Research Interests: Biology, Risk, Medicine, Humans, Female, and 12 moreMale, Oral Cancer, Cervical Cancer, Middle Aged, Oral Squamous Cell Carcinoma (OSCC), Mouth Neoplasms, Precancerous Conditions, Genomic instability, Disease Progression, Comparative Genomic Hybridization, Cohort Studies, and Head and neck neoplasms
Research Interests:
Research Interests:
Research Interests:
Ectomesenchymal chondromyxoid tumor is a rare and benign neoplasm with a predilection for the anterior dorsal tongue. Despite morphologic heterogeneity, most cases are characterized by a proliferation of bland spindle cells with a... more
Ectomesenchymal chondromyxoid tumor is a rare and benign neoplasm with a predilection for the anterior dorsal tongue. Despite morphologic heterogeneity, most cases are characterized by a proliferation of bland spindle cells with a distinctive reticular growth pattern and myxoid stroma. The immunophenotype of these neoplasms is likewise variable; most cases express glial fibrillary acid protein and S100 protein, with inconsistent reports of keratin and myoid marker expression. The molecular pathogenesis is poorly understood; however, a subset of cases has been reported to harbor EWSR1 gene rearrangement. Following identification of an RREB1-MKL2 fusion gene by RNA Sequencing in an index patient, a retrospective review of additional cases of ectomesenchymal chondromyxoid tumors was performed to better characterize the clinical, immunohistochemical, and molecular attributes of this neoplasm. A total of 21 cases were included in this series. A marked predisposition for the dorsal tongue...
Research Interests:
Research Interests:
White lesions in the oral cavity are common and have multiple etiologies, some of which are also associated with dermatological disease. While most intraoral white lesions are benign, some are premalignant and/or malignant at the time of... more
White lesions in the oral cavity are common and have multiple etiologies, some of which are also associated with dermatological disease. While most intraoral white lesions are benign, some are premalignant and/or malignant at the time of clinical presentation, making it extremely important to accurately identify and appropriately manage these lesions. Due to their similar clinical appearances, it may be difficult sometimes to differentiate benign white lesions from their premalignant/malignant counterparts. This review will discuss many of the most common intraoral white lesions including their clinical presentation, how to make an accurate diagnosis, and effective treatment and management strategies.
Research Interests:
Research Interests:
At Windber Research Institute we have started research programs that use artificial neural networks (ANNs) in the study of breast cancer in order to identify heterogeneous data predictors of patient disease stages. As an initial effort,... more
At Windber Research Institute we have started research programs that use artificial neural networks (ANNs) in the study of breast cancer in order to identify heterogeneous data predictors of patient disease stages. As an initial effort, we have chosen matrix metalloproteinases (MMPs) as potential biomarker predictors. MMPs have been implicated in the early and late stage development of breast cancer.
Research Interests:
It has been shown that inhibition of cyclooxygenase 2 (COX-2) may cause growth arrest and reduced tumour formation in some human cancers; however, the mechanism is not fully known. In this study, we used an oral squamous cell carcinoma... more
It has been shown that inhibition of cyclooxygenase 2 (COX-2) may cause growth arrest and reduced tumour formation in some human cancers; however, the mechanism is not fully known. In this study, we used an oral squamous cell carcinoma cell line to study growth inhibition and changes in critical cell cycle-regulating proteins induced by the selective COX-2 inhibitor celecoxib. Using cell viability assay, we established the optimal in vitro inhibitory dose of celecoxib and showed that inhibition of COX-2 markedly induces the expression of p27kip1, p21, waf1, and the F-box protein skp2. These results add new experimental data to our knowledge of the mechanism of cyclooxygenases on neoplastic cells.
Research Interests:
Research Interests:
Research Interests:
... of juvenile hyaline fibromatosis have been reported, making this non-neoplastic disorder very rare ... Gingival fibromatosis grows slowly, mainly causing difficulty in speaking and in eating. ... first described in 1995 as a... more
... of juvenile hyaline fibromatosis have been reported, making this non-neoplastic disorder very rare ... Gingival fibromatosis grows slowly, mainly causing difficulty in speaking and in eating. ... first described in 1995 as a distinctive orbital tumor occurring exclusively in male adults (37 ...
Research Interests:
Research Interests:
Sjögren&amp;amp;amp;amp;amp;amp;#39;s syndrome is an autoimmune disorder in which patients have a well-recognized risk of developing malignant lymphoma. Although some clinical parameters may herald the onset of lymphoma, few reliable... more
Sjögren&amp;amp;amp;amp;amp;amp;#39;s syndrome is an autoimmune disorder in which patients have a well-recognized risk of developing malignant lymphoma. Although some clinical parameters may herald the onset of lymphoma, few reliable histologic or molecular markers are available that predict progression to a malignant lymphoproliferative disorder. The purpose of this study was to identify the prevalence of immunoglobulin heavy chain monoclonality in labial gland biopsies of patients with Sjögren&amp;amp;amp;amp;amp;amp;#39;s syndrome and to compare this to clinical outcome. The polymerase chain reaction was applied to 76 sequential labial salivary gland biopsies from patients under investigation for Sjögren&amp;amp;amp;amp;amp;amp;#39;s syndrome. A seminested polymerase chain reaction technique was used on DNA extracted from formalin-fixed, paraffin-embedded tissue to amplify the V-D-J region of the immunoglobulin heavy chain gene. Thirty-four randomly selected labial salivary glands that showed nonspecific sialadenitis from patients without Sjögren&amp;amp;amp;amp;amp;amp;#39;s syndrome were used as controls. Monoclonality, as defined by a single band on polyacrylamide gel electrophoresis was detected in 11 cases (14.5%). Of cases that showed monoclonality, four patients were subsequently diagnosed with extrasalivary lymphoma. In each case the rearranged bands in the lip biopsy and the lymphoma were the same size. In one patient who later developed lymphoma, a monoclonal rearranged immunoglobulin band was not identified. In addition, no cases of the translocation t(14;18) were identified by polymerase chain reaction in any of the lip biopsies showing heavy chain monoclonality or in any of the extrasalivary gland lymphomas. These results suggest that monoclonal immunoglobulin heavy chain gene rearrangements are a relatively common finding in patients with Sjögren&amp;amp;amp;amp;amp;amp;#39;s syndrome and may prove to be a useful marker for predicting the progression to, and early detection of malignant lymphoma.
Research Interests:
Angiokeratoma is a rare, cutaneous disorder that typically occurs at multiple sites and is often associated with a number of metabolic disorders. Although solitary cutaneous forms have been reported, to date localized lesions within the... more
Angiokeratoma is a rare, cutaneous disorder that typically occurs at multiple sites and is often associated with a number of metabolic disorders. Although solitary cutaneous forms have been reported, to date localized lesions within the oral cavity have not been described. We report on an 82-year-old man with a history of squamous cell carcinoma of the ear and scalp who also had a solitary pigmented lesion of the oral cavity. Excisional biopsy of the buccal mucosal lesion showed features consistent with angiokeratoma. We report the first intra-oral solitary angiokeratoma and review the clinical and pathologic features of this unusual condition.