Prognostic impact of autoimmune disease in oral cavity squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: Recent literature has highlighted the role of the host in the prognosis of oral squamous cell carcinoma (OSCC). In this study, we retrospectively examined the impact of autoimmune (AI) disorders as an aspect of the host status on survival outcomes in OSCC patients. METHODS: From a departmental database of OSCC patients (n = 1369), 123 patients with an AI disorder were identified. AI and no-AI groups were compared for survival outcomes. RESULTS: There were no significant differences in survival between groups for overall survival, disease-specific survival, local, regional, and distant recurrence-free probabilities. However, survival and recurrence-free probabilities were poorer in the AI group versus the no AI group. CONCLUSION: Patients with AI disease trended towards worse outcomes. This suggests immune dysregulation in these patients may impact oncologic outcomes.

Nodal characteristics associated with adverse prognosis in oral cavity cancer are linked to host immune status.

BACKGROUND AND OBJECTIVE: Nodal metastasis is one of the strongest predictors of outcomes in oral cavity squamous cell carcinomas (OSCC). The aim was to analyze the interplay of nodal characteristics in OSCC prognosis. METHODS: In this retrospective cohort study we included OSCC patients treated with primary surgery including neck dissection between 2005 and 2015 (n = 619). Disease-specific survival (DSS) was the primary endpoint. Optimal cutoffs were identified using recursive-partitioning analysis (RPA). A novel characteristic-metastatic focus-to-lymph node size ratio (MLR)-was introduced. We compared the American Joint Committee on Cancer, Eighth Edition (AJCC8) pN categories to a new categorization. RESULTS: Patients with higher neutrophil-to-lymphocyte ratio had more adverse nodal characteristics. All nodal characteristics were significant predictors of DSS in univariable analysis. In multivariable analysis, only number of positive nodes and MLR remained significant. An RPA including all nodal covariates confirmed the results. Compared with AJCC8, our RPA categorization had better hazard discrimination (0.681 vs. 0.598), but poorer balance value (0.783 vs. 0.708). CONCLUSION: Patients with higher neutrophil-to-lymphocyte ratio had more adverse nodal characteristics. Total number of metastatic lymph nodes is the strongest predictor of outcomes in OSCC. MLR is a more powerful predictor than metastatic lymph node size or metastatic focus size alone.

Autoimmune disease and oral squamous cell carcinoma: A systematic review.

BACKGROUND: Oral cancer is typically related to environmental carcinogen exposure including tobacco and alcohol. Other less investigated risk factors may be related to a suppressed or dysregulated immune state, and in oral cancer, various levels of immune dysregulation have been found to affect survival and recurrence rates. The rationale for this systematic review was to investigate the possible role that a growing chronic host condition like an autoimmune disease may play in this disease. METHODS: A systematic search of the literature was carried out using four electronic databases in order to identify original research of any analytic study design type that investigated the relationship between autoimmune disease and oral cancer. Out of 1,947 identified records, 24 observational studies were included for qualitative synthesis. RESULTS: The studies varied in end points ranging from overall survival (OS), standardized incidence ratio (SIR), and hazard ratio (HR). Due to the heterogenous sampling of studies even within the same study design group, a meta-analysis was not employed. The current state of the literature is varied and heterogenous in both study design and endpoints. CONCLUSION: Major limitations existed introducing significant bias especially in determining cancer risk such as lack of information surrounding known etiologic risk factors such as alcohol and tobacco consumption. Despite these limitations, a signal was seen between autoimmune disease and oral cancer outcomes and risk. Future studies investigating the relationship between autoimmune disease and oral cancer in a more focused and quantitative manner are therefore needed.

An optimized purification protocol for enzymatically synthesized S-adenosyl-L-methionine (SAM) for applications in solution state infrared spectroscopic studies.

S-adenosyl-L-methionine (SAM) is an abundant biomolecule used by methyltransferases to regulate a wide range of essential cellular processes such as gene expression, cell signaling, protein functions, and metabolism. Despite considerable effort, there remain many specificity challenges associated with designing small molecule inhibitors for methyltransferases, most of which exhibit off-target effects. Interestingly, NMR evidence suggests that SAM undergoes conformeric exchange between several states when free in solution. Infrared spectroscopy can detect different conformers of molecules if present in appreciable populations. When SAM is noncovalently bound within enzyme active sites, the nature and the number of different conformations of the molecule are likely to be altered from when it is free in solution. If there are unique structures or different numbers of conformers between different methyltransferase active sites, solution-state information may provide promising structural leads to increase inhibitor specificity for a particular methyltransferase. Toward this goal, frequencies measured in SAM's infrared spectra must be assigned to the motions of specific atoms via isotope incorporation at discrete positions. The incorporation of isotopes into SAM's structure can be accomplished via an established enzymatic synthesis using isotopically labeled precursors. However, published protocols produced an intense and highly variable IR signal which overlapped with many of the signals from SAM rendering comparison between isotopes challenging. We observed this intense absorption to be from co-purifying salts and the SAM counterion, producing a strong, broad signal at 1100 cm-1. Here, we report a revised SAM purification protocol that mitigates the contaminating salts and present the first IR spectra of isotopically labeled CD3-SAM. These results provide a foundation for isotopic labeling experiments of SAM that will define which atoms participate in individual molecular vibrations, as a means to detect specific molecular conformations.

Engineering benefits of replacing natural sand with manufactured sand in landfill construction.

Translational sliding failures in landfills are often triggered by inadequate shear strength of interfaces in liners and covers. Geosynthetic Clay Liners (GCL) are used in different components of landfills to contain the leachate. GCLs are usually placed above a compacted sand subgrade to develop higher shear resistance. In the context of depleting natural sand resources, the present study explores the feasibility of replacing natural sand with manufactured sand (Msand) in landfill construction. Interface shear tests were performed on GCL in contact with river sand and Msand of similar gradation to evaluate the shear strength at different normal stresses and hydration conditions. It is found that Msand provides higher interface shear strength with GCL compared to river sand. Digital image analysis of tested specimens of GCL showed that variation in particle morphology of the two sands has direct influence on the microlevel interaction mechanisms governing the shear strength. Quantification of morphological parameters showed that Msand particles are angular and rough compared to natural sand particles, leading to higher particle interlocking. Hydration of the GCL reduced the interface shear strength, the effect being less in case of Msand. The study highlights that replacement of natural sand with Msand has added benefits.

Peripheral blood values as predictors of autoimmune status in oral cavity squamous cell carcinoma.

BACKGROUND: Recent literature has highlighted the role of the host in prognosis in oral squamous cell carcinoma (OSCC). Autoimmune (AI) disease represents a macroscopic depiction of host status. The goal of this study was to predict an AI "status" and to analyze the utility of this "status" as a prognostic indicator in OSCC. METHODS: From a departmental database of OSCC patients (n = 1377), 125 patients with an AI disorder were identified. PBL values were obtained and standardized for analysis. A LASSO regression model was used to determine the best predictors of AI status and an AI score was developed. The score was then analyzed across various survival endpoints. RESULTS: When AI score was divided into a binary variable, patients in the highest quartile had a significantly worse overall survival (OS), local recurrence-free (LRFP) and distant recurrence-free probability (DRFP). Survival curves showed significant differences for OS, DSS, LRFP, and DRFP. CONCLUSIONS: AI diseases are immune dysregulations that could play a role in prognosis. Therefore, development of an AI score is necessary to depict host status in a ubiquitous manner. AI score as a binary variable may be more utilitarian in a clinical setting, compared to the continuous score. This novel tool needs validation and integration into more tumor and host characteristics. This investigation showed utility of such a score, similar to PBL data in OSCC prognosis. Future studies should incorporate other relevant variables known to affect outcome and implement a more comprehensive predictive model.

Host Factors Independently Associated With Prognosis in Patients With Oral Cavity Cancer.

Importance: The association and interaction of host characteristics with prognosis in patients with oral cavity squamous cell carcinoma (OSCC) are poorly understood. There is increasing evidence that host characteristics are associated with treatment outcomes of many cancers. Objectives: To examine the host factors associated with prognosis in patients with OSCC and their interactions to create a numerical index that quantifies the prognostic capacity of these host characteristics. Design, Setting, and Participants: This retrospective cohort study included patients with OSCC treated surgically at a tertiary care center from January 1, 1998, to December 31, 2015. From a departmental OSCC database of 1377 previously untreated patients, 68 patients with missing data on any host variable of interest within a month before the start of treatment were excluded, leaving 1309 patients. Data analysis was performed from October 21, 2019, to December 10, 2019. Exposure: Primary surgery for OSCC. Main Outcomes and Measures: Overall survival (OS) was the primary end point, and disease-specific survival (DSS) was the secondary end point. Optimal cutoffs for each variable were identified using recursive-partitioning analysis with the classification and regression tree method using OS as the dependent variable. Body mass index (BMI) and pretreatment peripheral blood leukocyte count, platelet count, hemoglobin level, and albumin level were analyzed. A host index (H-index) was developed using independent factors associated with OS. Results: A total of 1309 patients (731 [55.8%] male; mean [SD] age, 62 [14.3] years) participated in the study. When including all the host-related factors in a multivariable analysis, all except BMI (hazard ratio [HR], 1.14; 95% CI, 0.80-1.63) were independently associated with outcomes. For example, compared with a hemoglobin level of 14.1 g/dL or greater, the HR for a level of 12.9 to 14.0 g/dL was 1.42 (95% CI, 1.13-1.77) and for a level of 12.8 g/dL or less was 1.51 (95% CI, 1.18-1.94), and compared with an albumin level of 4.3 g/dL or greater, the HR for a level of 3.7 to 4.2 g/dL was 1.18 (95% CI, 0.95-1.45) and for a level of 3.6 g/dL or less was 3.64 (95% CI, 2.37-5.58). An H-index of 1.4 or less was associated with a 74% 5-year OS, an H-index of 1.5 to 3.5 with a 65% 5-year OS, and an H-index of 3.6 or higher with a 38% 5-year OS; for DSS, the 5-year survival was 84%, 80%, and 64%, respectively. Compared with patients with an H-index score of 1.4 or less, patients with H-index scores of 1.5 to 3.5 (hazard ratio, 1.474; 95% CI, 1.208-1.798) and 3.6 or higher (hazard ratio, 3.221; 95% CI, 2.557-4.058) had a higher risk of death. Conclusions and Relevance: The findings suggest that pretreatment values of neutrophils, monocytes, lymphocytes, hemoglobin, and albumin are independently associated with prognosis in patients with OSCC. The interactions between these host factors were incorporated into a novel H-index that quantified the prognostic capacity of host characteristics associated with OSCC.