A5076508788- Head and Neck Cancer Studies
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Cervical Cancer and HPV Research
- Cancer-related Molecular Pathways
- Head and Neck Surgical Oncology
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- Molecular Biology Techniques and Applications
- Lung Cancer Treatments and Mutations
- Immunotherapy and Immune Responses
- Cell Adhesion Molecules Research
- Peptidase Inhibition and Analysis
- Cancer Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- Cancer Cells and Metastasis
- Genetic factors in colorectal cancer
- Cancer Research and Treatments
- Genomic variations and chromosomal abnormalities
- Salivary Gland Tumors Diagnosis and Treatment
- Virus-based gene therapy research
- Neuropeptides and Animal Physiology
- RNA Interference and Gene Delivery
- Cancer Immunotherapy and Biomarkers
University of Michigan
2014-2023
Michigan Center for Translational Pathology
2007-2023
The University of Texas MD Anderson Cancer Center
2011-2023
York University
2023
UPMC Health System
2023
Tokyo Medical and Dental University
2023
University of Pittsburgh Medical Center
2023
University of Colorado Health
2023
Cornell University
2023
Michigan United
2013-2022
X-ray based computed tomography (CT) is among the most convenient imaging/diagnostic tools in hospitals today terms of availability, efficiency, and cost. However, contrast to magnetic resonance imaging (MRI) various nuclear medicine modalities, CT not considered a molecular modality since targeted molecularly specific agents have yet been developed. Here we describe platform that enables, for first time, cancer detection at cellular level with standard clinical CT. The method on gold...
Wnt signaling is one of the key oncogenic pathways in multiple cancers, and targeting this pathway an attractive therapeutic approach. However, success has been limited because lack agents for targets a defined patient population that would be sensitive to inhibitor. We developed screen small molecules block secretion. This effort led discovery LGK974, potent specific small-molecule Porcupine (PORCN) PORCN membrane-bound O-acyltransferase required dedicated palmitoylation ligands, necessary...
Purpose To prospectively identify markers of response to therapy and outcome in an organ-sparing trial for advanced oropharyngeal cancer. Patients Methods Pretreatment biopsies were examined expression epidermal growth factor receptor (EGFR), p16, Bcl-xL, p53 as well mutation. These assessed association with high-risk human papillomavirus (HPV), therapy, survival. Patient variables included smoking history, sex, age, primary site, tumor stage, nodal status. Results EGFR was inversely...
We studied how frequently patients with malignant melanoma have specific antibody to cell surface antigens of cultured autologous cells as demonstrated by mixed hemadsorption assays. Of 35 over periods ranging from 1 36 months Stage II, III, and IV disease, two showed consistent high titered reactivity against cells, less intermediate reactivity, seven sporatic, low the remainder were consistently negative. A detailed analysis was carried out sera one patient sufficiently titer cells. By...
Abstract Background In accord with the cancer stem cell (CSC) theory, only a small subset of cells are capable forming tumors. We previously reported that CD44 isolates tumorigenic from head and neck squamous (HNSCC). Recent studies indicate aldehyde dehydrogenase (ALDH) activity may represent more specific marker CSCs. Methods Six primary HNSCCs were collected. Cells high low ALDH (ALDH /ALDH ) isolated. populations implanted into NOD/SCID mice monitored for tumor development. Results...
Purpose To test induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CRT) or surgery/radiotherapy (RT) for advanced oropharyngeal cancer and to assess the effect of human papilloma virus (HPV) on response outcome. Patients Methods Sixty-six patients (51 male; 15 female) with stage III IV squamous cell carcinoma oropharynx (SCCOP) were treated one cycle cisplatin (100 mg/m 2 ) carboplatin (AUC 6) fluorouracil (1,000 /d 5 days) select candidates CRT. Those achieving a greater...
Purpose To assess clinical and functional results of chemoradiotherapy for oropharyngeal cancer (OPC), utilizing intensity-modulated radiotherapy (IMRT) to spare the important swallowing structures reduce post-therapy dysphagia. Patients Methods This was a prospective study weekly chemotherapy (carboplatin dosed at one times area under curve [AUC, AUC 1] paclitaxel 30 mg/m 2 ) concurrent with IMRT aiming noninvolved parts structures: pharyngeal constrictors, glottic supraglottic larynx,...
Because immune responses within the tumor microenvironment are important predictors of biology, correlations types infiltrating lymphocytes (TILs) with clinical outcomes were determined in 278 patients head and neck squamous cell carcinoma (HNSCC).Infiltrating levels CD4 (helper T cells), CD8 (cytotoxic/suppressor FoxP3 (regulatory CD68 (myeloid-derived suppressor cells,) CD1a (Langerhans) cells measured tissue microarrays (TMAs). Cox models tested associations patient after adjusting for...
The goal of this study was to examine the effect tobacco use on disease recurrence (local/regional recurrence, distant metastasis, or second primary) among patients with human papillomavirus (HPV)-positive squamous cell carcinoma oropharynx (SCCOP) following a complete response chemoradiation therapy.Between 1999 and 2007, 124 advanced SCCOP (86% stage IV) adequate tumor tissue for HPV analysis who were enrolled in one two consecutive University Michigan treatment protocols prospectively...
Abstract Background. We established multiple University of Michigan Squamous Cell Carcinoma (UM‐SCC) cell lines. With time, these have been distributed to other labs all over the world. Recent scientific discussions noted need confirm origin and identity lines in grant proposals journal articles. genotyped UM‐SCC our collection their unique identity. Method. Early‐passage were photographed. Results . Thus far, 73 head neck (from 65 donors, including 21 from 17 females) genotyped. In 7 cases,...
Abstract Purpose: Human cell lines are useful for studying cancer biology and preclinically modeling therapy, but can be misidentified cross-contamination is unfortunately common. The purpose of this study was to develop a panel validated head neck representing the spectrum tissue sites histologies that could used molecular, genetic, phenotypic diversity cancer. Methods: A 122 clinically phenotypically diverse from squamous carcinoma, thyroid cancer, cutaneous adenoid cystic oral...
Abstract The incidence of human papillomavirus (HPV)–related oropharynx cancer has steadily increased over the past two decades and now represents a majority oropharyngeal cases. Integration HPV genome into host is common event during carcinogenesis that clinically relevant effects if viral early genes are transcribed. Understanding impact integration on clinical outcomes head neck squamous cell carcinoma (HNSCC) critical for implementing deescalated treatment approaches HPV+ HNSCC patients....
E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent, homotypic cell-cell adhesion and plays an important role in maintaining the normal phenotype of epithelial cells. Disruption activity cells correlates with formation metastatic tumors. Decreased adhesive function may be implemented number ways including: (a) decreased expression E-cadherin; (b) mutations gene encoding or (c) genes encode catenins, proteins link cadherins to cytoskeleton are essential for cadherin...
We characterized the breakpoints, gains, and losses of chromosome material in squamous cell carcinomas head neck region from 29 patients. Cell lines were karyotyped 1/3 cases, direct preparations or early vitro harvests 1/3, both cases. GTG-banding was employed all as C-banding RBG- AgNOR-staining most. Some tumors near-diploid others near-tetraploid, but many had mixed populations, with diploid, tetraploid, octoploid subclones representing essentially same karyotypic pattern. The most...
• Squamous cell carcinoma is the most common of human cancers, and yet because it poorly represented by cultured lines, little known about characteristic biology cellsurface antigenic phenotypes such tumors. To develop a continuously available source squamous for repeated reproducible serologic analysis better understanding its biologic characteristics, tissue culture methods nude mice were used to establish new lines carcinoma. Special media, serum supplements from several sources, handling...
Oncogenic human papillomaviruses (HPV) are associated with nearly all cervical cancers and increasingly important in the etiology of oropharyngeal tumors. HPV-associated head neck squamous cell carcinomas (HNSCC) have distinct risk profiles appreciate a prognostic advantage compared to HPV-negative HNSCC. Promoter hypermethylation is widely recognized as mechanism progression HNSCC, but extent which this consistent between HPV(+) HPV(-) tumors unknown. To investigate epigenetic regulation...
The incidence of human papillomavirus–positive (HPV+) head and neck squamous cell carcinoma (HNSCC) has surpassed that cervical cancer is projected to increase rapidly until 2060. coevolution HPV with transforming epithelial cells leads the shutdown host immune detection. Targeting proximal viral nucleic acid–sensing machinery an evolutionarily conserved strategy among viruses enable evasion. However, E7 from dominant subtype 16 in HNSCC shares low homology HPV18 E7, which was shown inhibit...
Purpose: The response rates of Head and Neck Squamous Cell Carcinoma (HNSCC) to checkpoint blockade are below 20%. We aim develop a mechanism-based vaccine prevent HNSCC immune escape.Experimental Design: performed RNA-Seq sensitive resistant cells discover central pathways promoting resistance killing. Using biochemistry, animal models, microarray, cell deconvolution, we assessed the role SOX2 in inhibiting STING-type I interferon (IFN-I) signaling-mediated antitumor immunity. To bypass...
There is substantial heterogeneity within human papillomavirus (HPV)-associated head and neck cancer (HNC) tumors that predispose them to different outcomes; however, the molecular in this subgroup poorly characterized due various historical reasons.We performed unsupervised gene expression clustering on deeply annotated (transcriptome genome) HPV(+) HNC samples from two cohorts (84 total primary tumors), including 18 HPV(-) samples, discover subtypes characterize differences between...
Inverted sinonasal papilloma (ISP) is a locally aggressive neoplasm associated with squamous cell carcinoma (SNSCC) in 10% to 25% of cases. To date, no recurrent mutations have been identified ISP or SNSCC. Using targeted next-generation sequencing and Sanger sequencing, we activating EGFR 88% 77% ISP-associated Identical genotypes were found matched pairs SNSCC, providing the first genetic evidence biologic link between these tumors. not exophytic oncocytic papillomas non-ISP-associated...
Abstract Background Human papillomavirus (HPV) has been detected in keratinizing nasopharyngeal carcinomas (NPCs); however, the relationship between HPV and Epstein–Barr virus (EBV) among whites with nonkeratinizing NPCs remains unclear. The HPV, p16, EBV status was examined current University of Michigan patients NPC. Methods From 2003 to 2007, 89 patients, 84 oropharyngeal cancer (OPC) 5 NPC, were enrolled an organ‐sparing trial. Biopsy tissues from all evaluated for p16 expression. A...