Browsing by Subject "Dysplasia"

Now showing 1 - 6 of 6
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    Clinical Management Update of Oral Leukoplakia: A Review From the American Head and Neck Society Cancer Prevention Service
    (Wiley, 2025) Gates, James C.; Abouyared, Marianne; Shnayder, Yelizaveta; Farwell, D. Gregory; Day, Andrew; Alawi, Faizan; Moore, Michael; Holcomb, Andrew J.; Birkeland, Andrew; Epstein, Joel; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Background: Oral potentially malignant disorders (OPMDs) occur in up to 4%-5% of the population, of which oral leukoplakia (OL) is the most common subtype. Predicting high-risk OL remains a challenge. Early diagnosis and effective treatment are thought to be of paramount importance to improve outcomes. Methods: We searched PubMed and Clinicaltrials.gov data for updates in the clinical management of OL from 2015 to current. Results: Recent publication of large cohorts of patients with OL aids in counseling patients regarding risk of malignant transformation. Management for OL includes surveillance, excision, and laser surgery, as well as local and systemic approaches to chemoprevention. Several new entities show promise regarding candidate biomarkers, chemoprevention agents, and diagnostic adjuncts, though all require further validation. Conclusion: This update serves to further inform clinical management of OL and provide impetus for future investigations.
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    Diagnostic efficacy of novel cephalometric parameters for the assessment of vertical skeletal dysplasia
    (Tabriz University of Medical Sciences, 2022) Gandhi, Kaveri Kranti; Rai, Anshu; Periodontology, School of Dentistry
    Background. An accurate diagnosis of vertical skeletal abnormalities presents several challenges. Specific cephalometric parameters can be effectively used for this purpose; however, the diagnostic accuracy of these parameters has not been entirely ascertained. This study examines the effectiveness of two novel cephalometric parameters for diagnosing vertical dysplasia. Methods. In this retrospective study, orthodontic patients were distributed into three study groups: average growth (AGG), horizontal growth (HGG), and vertical growth (VGG). The efficacies of the sum of angles (maxillary, mandibular, and ramal) and the height ratio (lower anterior facial height [LAFH]/upper anterior facial height [UAFH]) in identifying different growth patterns were examined. Receiver operating characteristic (ROC) curves were employed to assess the diagnostic precision quantitatively. Results. A total of 150 patients were included and divided equally among the three study groups. The ramal and mandibular angles varied across AGG, HGG, and VGG; however, the maxillary angle and the sum of these three angles did not vary significantly. There was a substantial variance in LAHF, UAHF, and their ratio in the three groups. The height ratio had 88% and 92% sensitivity to diagnose VGG and HGG, with cut-off values of 46 and 34, respectively (P<0.001). Conclusion. Height ratio values varied considerably depending on the facial growth patterns, suggesting its efficacy as a diagnostic tool for skeletal dysplasia, with greater reliability for positive treatment outcomes.
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    A Randomized Phase II Trial of Pioglitazone for Lung Cancer Chemoprevention in High Risk Current and Former Smokers
    (American Association for Cancer Research, 2019-10) Keith, Robert L.; Blatchford, Patrick J.; Merrick, Daniel T.; Bunn, Paul A., Jr.; Bagwell, Brandi; Dwyer-Nield, Lori D.; Jackson, Mary K.; Geraci, Mark W.; Miller, York E.; Medicine, School of Medicine
    Lung cancer chemoprevention, especially in high-risk former smokers, has great potential to reduce lung cancer incidence and mortality. Thiazolidinediones prevent lung cancer in preclinical studies, and diabetics receiving thiazolidinediones have lower lung cancer rates which led to our double-blind, randomized, phase II placebo-controlled trial of oral pioglitazone in high risk current or former smokers with sputum cytologic atypia or known endobronchial dysplasia. Bronchoscopy was performed at study entry and after completing of six months of treatment. Biopsies were histologically scored, and primary endpoint analysis tested worst biopsy scores (Max) between groups; Dysplasia index (DI) and average score (Avg) changes were secondary endpoints. Biopsies also received an inflammation score. The trial accrued 92 subjects (47 pioglitazone, 45 placebo), and 76 completed both bronchoscopies (39 pioglitazone, 37 placebo). Baseline dysplasia was significantly worse for current smokers, and 64% of subjects had mild or greater dysplasia at study entry. Subjects receiving pioglitazone did not exhibit improvement in bronchial dysplasia. Former smokers treated with pioglitazone exhibited a slight improvement in Max, while current smokers exhibited slight worsening. While statistically significant changes in Avg and DI were not observed in the treatment group, former smokers exhibited a slight decrease in both Avg and DI. Negligible Avg and DI changes occurred in current smokers. A trend towards decreased Ki-67 labeling index occurred in former smokers with baseline dysplasia receiving pioglitazone. While pioglitazone did not improve endobronchial histology in this high-risk cohort, specific lesions showed histologic improvement and further study is needed to better characterize responsive dysplasia.
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    Retrospective, observational, cross-sectional study of detection of recurrent Barrett's esophagus and dysplasia in post-ablation patients with adjunctive use of wide-area transepithelial sample (WATS-3D)
    (Hellenic Society of Gastroenterology, 2022) Fatima, Hala; Wajid, Maryiam; Hamade, Nour; Han, Yan; Kessler, William; Dewitt, John; Rex, Douglas; Imperiale, Thomas; Medicine, School of Medicine
    Background: Barrett's esophagus (BE) and dysplasia are often missed by Seattle protocol biopsies (SPB). Wide-area transepithelial sampling with 3-dimensional computer-assisted analysis (WATS-3D) with SPB improves detection in treatment-naïve patients. We aimed to determine to what extent WATS-3D adds to SPB in the detection of non-dysplastic BE (NDBE) and dysplasia in patients undergoing post-endoscopic eradication therapy (EET). Methods: This retrospective, observational, cross-sectional study included patients who presented for post-EET surveillance with SPB and WATS-3D sampling from April 2019 to February 2020. BE patients with no previous EET were excluded. For the outcomes of NDBE and any dysplastic/neoplastic finding, we calculated both relative and absolute increases in yield by WATS-3D over SBP. Results: In 78 patients [mean age 68±10.4 years, 66 (84.6%) male], the prevalence of NDBE, any dysplastic/neoplastic finding, and any abnormality (NDBE or dysplasia/neoplasia) were 53.85%, 10.26%, and 55.13%. The absolute increase in yield of NDBE with WATS-3D over SPB was 26.9% (95% confidence interval [CI] 17.95-37.18%), with the number needed to treat (NNT) 3.71 (95%CI 2.69-5.57) and a relative increase in yield of 100% (95%CI 53.33-188.25%). For dysplasia/neoplasia, the absolute increase in yield was 6.4% (95%CI 1.28-12.82%), NNT 15.6 (95%CI 7.8-78.0), and relative increase of 167% (95%CI 33.33%-infinity). For any abnormal finding, the absolute increase in yield was 26.9% (95%CI 16.67-37.18%), NNT 3.71 (95%CI 2.69-6.00), and relative increase in yield 95% (95%CI 50-176.92%). Conclusions: WATS-3D with SPB improves the detection of residual/recurrent BE and dysplasia in post-ablation BE. However, randomized controlled trials are needed to validate these findings.
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    The tumor suppressing roles of tissue structure in cervical cancer development
    (2012-12) Nguyen, Hoa Bich; Quilliam, Lawrence; Brutkiewicz, Randy R.; Harrington, Maureen A.; Kapur, Reuben; Wells, Clark D.
    Cervical cancer is caused by the persistent infection of human papilloma virus (HPV) in the cervix epithelium. Although effective preventative care is available, the widespread nature of infection and the variety of HPV strains unprotected by HPV vaccines necessitate a better understanding of the disease for development of new therapies. A major tumor suppressing mechanism is the inhibition of cell division by tissue structure; however, the underlining molecular circuitry for this regulation remains unclear. Recently, the Yap transcriptional co-activator has emerged as a key growth promoter that mediates contact growth arrest and limits organ size. Thus, we aimed to uncover upstream signals that connect tissue organization to Yap regulation in the inhibition of cervical cancer. Two events that disrupt tissue structure were examined including the loss of the tumor suppressor LKB1 and the expression of the viral oncogene HPV16-E6. We identified that Yap mediates cell growth regulation downstream of both LKB1 and E6. Restoration of LKB1 expression in HeLa cervical cancer cells, which lack this tumor suppressor, or shRNA knockdown of LKB1 in NTERT immortalized normal human dermal keratinocytes, demonstrated that LKB1 promotes Yap phosphorylation, nuclear exclusion, and proteasomal degradation. The ability of phosphorylation-defective Yap mutants to rescue LKB1 phenotypes, such as reduced cell proliferation and cell size, suggest that Yap inhibition contributes to LKB1 tumor suppressor function(s). Interestingly, LKB1’s suppression of Yap activity required neither the canonical Yap kinases, Lats1/2, nor metabolic downstream targets of LKB1, AMPK and mTORC1. Instead, the scaffolding protein NF2 was required for LKB1 to induce a specific actin cytoskeleton structure that associates with Yap suppression. Meanwhile, HPV16-E6 promoted Yap activation in all stages of keratinocyte differentiation. E6 activated the Rap1 small GTPase, which in turn promoted Yap activity. Since Rap1 does not mediate differentiation inhibition caused by E6, E6 may play a role in promoting cell growth through Rap1-Yap activation rather than preventing growth arrest through the disruption of differentiation. Altogether, the LKB1-NF2-Yap and E6-Rap1-Yap pathways represent two examples of a novel phenomenon, whereby the structure of a cell directly influences its gene expression and proliferation.
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    XPC Protects against Carcinogen-Induced Histologic Progression to Lung Squamous Cell Carcinoma by Reduced Basal Epithelial Cell Proliferation
    (MDPI, 2024-04-13) Sears, Catherine R.; Zhou, Huaxin; Hulsey, Emily; Aidoo, Bea A.; Sandusky, George E.; Al Nasrallah, Nawar; Medicine, School of Medicine
    Lung squamous cell carcinoma (LUSC) is the second leading cause of lung cancer. Although characterized by high DNA mutational burdens and genomic complexity, the role of DNA repair in LUSC development is poorly understood. We sought to better understand the role of the DNA repair protein Xeroderma Pigmentosum Group C (XPC) in LUSC development. XPC knock-out (KO), heterozygous, and wild-type (WT) mice were exposed topically to N-nitroso-tris-chloroethylurea (NTCU), and lungs were evaluated for histology and pre-malignant progression in a blinded fashion at various time-points from 8-24 weeks. High-grade dysplasia and LUSC were increased in XPC KO compared with XPC WT NTCU mice (56% vs. 34%), associated with a higher mean LUSC lung involvement (p < 0.05). N-acetylcysteine pre-treatment decreased bronchoalveolar inflammation but did not prevent LUSC development. Proliferation, measured as %Ki67+ cells, increased with NTCU treatment, in high-grade dysplasia and LUSC, and in XPC deficiency (p < 0.01, ANOVA). Finally, pre-LUSC dysplasia developed earlier and progressed to higher histologic classification sooner in XPC KO compared with WT mice. Overall, this supports the protective role of XPC in squamous dysplasia progression to LUSC. Mouse models of early LUSC development are limited; this may provide a valuable model to study mechanisms of LUSC development and progression.