Elliot Abemayor

Salivary microRNA: Discovery, Characterization, and Clinical Utility for Oral Cancer Detection

Purpose: We have previously shown that a transcriptome is found in saliva and subpanels of these mRNAs can be used as oral cancer biomarkers. In this study, we measured the presence of microRNAs (miRNA) in saliva and determined their potential as an additional set of oral cancer biomarkers. Experimental Design: A total of 314 miRNAs were measured using reverse transcriptase-preamplification-quantitative PCR in 12 healthy controls. Degradation pattern of endogenous and exogenous saliva miRNAs were measured at room temperature over time. Selected miRNAs were validated in saliva of 50 oral squamous cell carcinoma patients and 50 healthy matched control subjects. Results: We detected ∼50 miRNAs in both the whole and supernatant saliva. Endogenous saliva miRNA degraded much slower compared with exogenous miRNA. Two miRNAs, miR-125a and miR-200a, were present in significantly lower levels (P < 0.05) in the saliva of oral squamous cell carcinoma patients than in control subjects. Conclusions: Both whole and supernatant saliva of healthy controls contained dozens of miRNAs, and similar to saliva mRNAs, these miRNAs are stable. Saliva miRNAs can be used for oral cancer detection. (Clin Cancer Res 2009;15(17):5473–7)

Salivary Transcriptome Diagnostics for Oral Cancer Detection

Purpose: Oral fluid (saliva) meets the demand for noninvasive, accessible, and highly efficient diagnostic medium. Recent discovery that a large panel of human RNA can be reliably detected in saliva gives rise to a novel clinical approach, salivary transcriptome diagnostics. The purpose of this study is to evaluate the diagnostic value of this new approach by using oral squamous cell carcinoma (OSCC) as the proof-of-principle disease. Experimental Design: Unstimulated saliva was collected from patients (n = 32) with primary T1/T2 OSCC and normal subjects (n = 32) with matched age, gender, and smoking history. RNA isolation was done from the saliva supernatant, followed by two-round linear amplification with T7 RNA polymerase. Human Genome U133A microarrays were applied for profiling human salivary transcriptome. The different gene expression patterns were analyzed by combining a t test comparison and a fold-change analysis on 10 matched cancer patients and controls. Quantitative polymerase chain reaction (qPCR) was used to validate the selected genes that showed significant difference (P < 0.01) by microarray. The predictive power of these salivary mRNA biomarkers was analyzed by receiver operating characteristic curve and classification models. Results: Microarray analysis showed there are 1,679 genes exhibited significantly different expression level in saliva between cancer patients and controls (P < 0.05). Seven cancer-related mRNA biomarkers that exhibited at least a 3.5-fold elevation in OSCC saliva (P < 0.01) were consistently validated by qPCR on saliva samples from OSCC patients (n = 32) and controls (n = 32). These potential salivary RNA biomarkers are transcripts of IL8, IL1B, DUSP1, HA3, OAZ1, S100P, and SAT. The combinations of these biomarkers yielded sensitivity (91%) and specificity (91%) in distinguishing OSCC from the controls. Conclusions: The utility of salivary transcriptome diagnostics is successfully demonstrated in this study for oral cancer detection. This novel clinical approach could be exploited to a robust, high-throughput, and reproducible tool for early cancer detection. Salivary transcriptome profiling can be applied to evaluate its usefulness for other major disease applications as well as for normal health surveillance.

Positron emission tomography: A new, precise imaging modality for detection of primary head and neck tumors and assessment of cervical adenopathy

Positron emission tomography (PET) has been shown to be effective in detecting intracranial malignancies based on cerebral glucose metabolism. To evaluate the ability of PET to detect extracranial head and neck neoplasms and cervical metastases, 16 patients with primary squamous cell carcinomas were examined. All patients received preoperative computerized tomography (CT) and magnetic resonance imaging (MRI) scans and underwent PET evaluation using intravenous 18F‐2‐fluoro‐2‐deoxy‐D‐glucose (FDG). Histopathologic analysis compared tumor invasion and positive lymph nodes with findings on MRI, CT, and PET images. All primary tumors were delineated by PET, while MRI and CT failed to detect one superficial tumor involving the anterior tongue. Ten nodes were detected by CT and MRI versus 12 nodes demonstrated by PET. PET is highly effective in detecting head and neck carcinomas as well as metastatic cervical lymph nodes. In addition, PET may be useful in evaluating postsurgery and postradiotherapy patients for recurrent and new primary tumors.

Rhinocerebral Mucormycosis: Evolution of the Disease and Treatment Options†

Rhinocerebral mucormycosis is recognized as a potentially aggressive and commonly fatal fungal infection. The classic presentation is involvement of nasal mucosa with invasion of the paranasal sinuses and orbit. Mucormycosis is most commonly seen in association with diabetic ketoacidosis, but disease demographics have changed with the onset of AIDS and the advent of powerful immunosuppressive drugs. Treatment includes aggressive debridement, systemic antifungal therapy, and control of underlying comorbid factors. Although surgical intervention remains essential, advances in medical therapy have permitted a more limited surgical approach to minimize functional loss without compromising survival. We present the UCLA experience with rhinocerebral mucormycosis from 1955 to 1995, with emphasis on the evolution of disease presentation and alternative treatment options.

Serum Circulating Human mRNA Profiling and Its Utility for Oral Cancer Detection

PURPOSE The purpose of this study is to explore the presence of informative RNA biomarkers from human serum transcriptome, and evaluate the serum transcriptome diagnostics for disease detection. Oral squamous cell carcinoma (OSCC) was selected as the proof-of-concept disease. PATIENTS AND METHODS Blood samples were collected from patients (n = 32) with primary T1/T2 OSCC and matched healthy patients (n = 35). Circulating RNA was isolated from serum and linearly amplified using T7 polymerase. Microarrays were applied for profiling transcriptome in serum from 10 cancer patients and controls. The differential gene expression was analyzed by combining the present calls, t tests, and fold-change statistics. Quantitative polymerase chain reaction (PCR) was used to validate the selected candidate RNA markers identified by microarray. Receiver operating characteristic curve and classification models were exploited to evaluate the diagnostic power of these markers for OSCC. RESULTS Human serum circulating mRNAs were presented by reverse transcriptase PCR. Microarray identified 2,623 +/- 868 probes assigned present calls in OSCC (n = 10) versus 1,792 +/- 165 in healthy patients (n = 10), indicating a higher complexity of serum transciptome in OSCC patients (P = .002, Wilcoxon test). Three hundred thirty-five serum RNAs exhibited significantly differential expression level between the two groups (P < .05, t test; fold > or = 2). Five cancer-related gene transcripts were consistently validated by quantitative PCR on serum from OSCC patients (n = 32) and controls (n = 35). The best combination of biomarkers yielded a receiver operating characteristic curve value of 88%, sensitivity (91%), and specificity (71%) in distinguishing OSCC. CONCLUSION The utility of serum transcriptome diagnostics is successfully demonstrated for OSCC detection. This novel concept could be developed as an adjunctive tool for disease diagnosis.

Surgery for Papillary Thyroid Carcinoma: Is Lobectomy Enough?

OBJECTIVE To further understanding of treatment of papillary thyroid carcinoma (PTC). DESIGN The Surveillance, Epidemiology, and End Results Program database was searched for patients who had undergone surgery for PTC. SETTING Areas covered by Surveillance, Epidemiology, and End Results population-based registries. PATIENTS Patients who had undergone PTC surgery between January 1, 1988, and December 31, 2001, were included in the study. MAIN OUTCOME MEASURES Disease-specific survival (DSS) and overall survival (OS). RESULTS Of the total 22,724 patients with PTC, 5964 patients underwent lobectomy. There were 2138 total and 471 disease-specific deaths. Controlling for tumor size, multivariate analysis revealed no survival difference between patients who had undergone total thyroidectomy and those who had undergone lobectomy. Increased tumor size, extrathyroidal extent, positive nodal status, and increased age displayed significantly worse DSS and OS (P < .001). Histologically, follicular PTC subtype did not affect DSS or OS. Patients who had received radioactive iodine had poorer DSS but improved OS. Patients undergoing external beam radiation therapy had poor DSS (hazard ratio, 4.48; 95% confidence interval, 3.30-6.06; P < .001) and OS (1.71; 1.42-2.07; P < .001). CONCLUSIONS The results of this study compel us to reinvestigate the current PTC surgical recommendations of total thyroidectomy based on tumor size because this may not affect survival across all populations. In addition, the current use of external beam radiation therapy for the treatment of PTC should be reexamined.

Prevalidation of Salivary Biomarkers for Oral Cancer Detection

Background: Oral cancer is the sixth most common cancer with a 5-year survival rate of approximately 60%. Presently, there are no scientifically credible early detection techniques beyond conventional clinical oral examination. The goal of this study is to validate whether the seven mRNAs and three proteins previously reported as biomarkers are capable of discriminating patients with oral squamous cell carcinomas (OSCC) from healthy subjects in independent cohorts and by a National Cancer Institute (NCI)-Early Detection Research Network (EDRN)-Biomarker Reference Laboratory (BRL). Methods: Three hundred and ninety-five subjects from five independent cohorts based on case controlled design were investigated by two independent laboratories, University of California, Los Angeles (Los Angeles, CA) discovery laboratory and NCI-EDRN-BRL. Results: Expression of all seven mRNA and three protein markers was increased in OSCC versus controls in all five cohorts. With respect to individual marker performance across the five cohorts, the increase in interleukin (IL)-8 and subcutaneous adipose tissue (SAT) was statistically significant and they remained top performers across different cohorts in terms of sensitivity and specificity. A previously identified multiple marker model showed an area under the receiver operating characteristic (ROC) curve for prediction of OSCC status ranging from 0.74 to 0.86 across the cohorts. Conclusions: The validation of these biomarkers showed their feasibility in the discrimination of OSCCs from healthy controls. Established assay technologies are robust enough to perform independently. Individual cutoff values for each of these markers and for the combined predictive model need to be further defined in large clinical studies. Impact: Salivary proteomic and transcriptomic biomarkers can discriminate oral cancer from control subjects. Cancer Epidemiol Biomarkers Prev; 21(4); 664–72. ©2012 AACR.

Radial forearm free flap pharyngoesophageal reconstruction.

Objectives This study evaluates the outcome of pharyngoesophageal reconstruction using radial forearm free flaps with regard to primary wound healing, speech, and swallowing in patients requiring laryngopharyngectomy.

Nasopharyngeal carcinoma: Treatment results with primary radiation therapy

One hundred three patients with nasopharyngeal carcinoma were treated with radiotherapy at UCLA Medical Center from January 1955 to December 1990. Overall survival, disease‐free survival, and local control rates were analyzed. In addition, survival from 1955 to 1978 and from 1979 to 1990 were evaluated. Overall 5‐ and 10‐year actuarial survival rates for all patients were 58% and 47%, respectively. Disease‐free survival rates at 3 and 5 years were 45% and 30%, respectively. Local, persistent, or recurrent disease in the nasopharynx was the primary cause of failure, occurring in 32% of patients and correlating with the initial tumor size (T stage). Twenty‐four percent of patients developed distant metastases, which correlated with nodal status but not with T stage. Seventy‐nine percent of patients failed either locally or distally by 4 years. Sex, race, age, and T and N stage categories were evaluated as prognostic variables in terms of survival. Control of primary disease is important in determining long‐term outcome. Modern imaging techniques have greatly assisted in the evaluation of disease extent and treatment options.

Postirradiation sarcoma of the head and neck

Background. With improvement in survival after cancer treatment, it is becoming increasingly important to study treatment‐related morbidity and mortality. Sarcoma can develop in the irradiated field after radiation therapy. The authors performed a study to estimate the risk, and compared the risk of sarcoma after radiation therapy with that of other treatment modalities used against cancer.