OBJECTIVES: To design and perform a simple surveillance on OLP patients based on colour-coded topography mouth maps (TMM).
MATERIALS AND METHODS: Three colour-coded TMM were employed: red for OLP in high risk oral mucosal sites, yellow for cases showing improvement and green for asymptomatic lesions at each recall visit. In this preliminary study, these were applied on 30 histologically confirmed OLP individuals attending the Oral Medicine Clinic at the Department of Oral Pathology, Oral Medicine and Periodontology, Faculty of Dentistry, University of Malaya. The sites and extent of OLP lesions were charted on either red, yellow or green TMM based on defined criteria. This surveillance evaluated OLP in relation to patientandapos;s age, race, gender, underlying systemic conditions, oral habits, initial onset of OLP, oral manifestations and presence/absence of clinically suspicious areas.
RESULTS: Study sample comprised 4 (13.3%) Malays, 9 (30.0%) Chinese and 17 (56.7%) Indians. Most OLP patients belong to the green TMM (n= 14, 46.6%) group followed by red (n= 11, 36.7%) and yellow (n= 5, 16.7%) groups. Of the 11 cases with red TMM, rebiopsy was performed on 4 cases but no dysplasia was detected. Any local confounding factors namely periodontal disease or faulty dental restorations were managed accordingly.
CONCLUSIONS: TMM is simple to use and aided the clinicians in terms of time saving and patient management. Hence, follow-up of OLP patients can be carried out more efficiently and appropriately. TMM can be used for surveillance of other oral precancerous lesions and conditions.
METHODS: We conducted transcriptome profiling on 32 colonic biopsies [11 long-duration UC, ≥20 years; and 21 short-duration UC, ≤5 years] using Affymetrix Human Transcriptome Array 2.0. Differentially expressed genes [fold change > 1.5, p < 0.05] and alternative splicing events [splicing index > 1.5, p < 0.05] were determined using the Transcriptome Analysis Console. KOBAS 3.0 and DAVID 6.8 were used for KEGG and GO analysis. Selected genes from microarray analysis were validated using qPCR.
RESULTS: There were 640 differentially expressed genes between both groups. The top ten upregulated genes were HMGCS2, UGT2A3 isoforms, B4GALNT2, MEP1B, GUCA2B, ADH1C, OTOP2, SLC9A3, and LYPD8; the top ten downregulated genes were PI3, DUOX2, VNN1, SLC6A14, GREM1, MMP1, CXCL1, TNIP3, TFF1, and LCN2. Among the 123 altered KEGG pathways, the most significant were metabolic pathways; fatty acid degradation; valine, leucine, and isoleucine degradation; the peroxisome proliferator-activated receptor signalling pathway; and bile secretion, which were previously linked with CAC. Analysis showed that 3560 genes exhibited differential alternative splicing between long- and short-duration UC. Among them, 374 were differentially expressed, underscoring the intrinsic relationship between altered gene expression and alternative splicing.
CONCLUSIONS: Long-duration UC patients have altered gene expressions, pathways, and alternative splicing events as compared with short-duration UC patients, and these could be further validated to improve our understanding of the pathogenesis of CAC.
RECENT FINDINGS: Several F-box containing proteins have been characterized either as tumor suppressors (FBXW8, FBXL3, FBXW8, FBXL3, FBXO1, FBXO4, and FBXO18) or as oncogenes (FBXO5, FBXO9, and SKP2). Besides, F-box members like βTrcP1 and βTrcP2, the ones with context-dependent functionality, have also been studied and reported. FBXW7 is a well-studied F-box protein and is a tumor suppressor. FBXW7 regulates the activity of a range of substrates, such as c-Myc, cyclin E, mTOR, c-Jun, NOTCH, myeloid cell leukemia sequence-1 (MCL1), AURKA, NOTCH through the well-known ubiquitin-proteasome system (UPS)-mediated degradation pathway. NOTCH signaling is a primitive pathway that plays a crucial role in maintaining normal tissue homeostasis. FBXW7 regulates NOTCH protein activity by controlling its half-life, thereby maintaining optimum protein levels in tissue. However, aberrations in the FBXW7 or NOTCH expression levels can lead to poor prognosis and detrimental outcomes in patients. Therefore, the FBXW7-NOTCH axis has been a subject of intense study and research over the years, especially around the interactome's role in driving cancer development and progression. Several studies have reported the effect of FBXW7 and NOTCH mutations on normal tissue behavior. The current review attempts to critically analyze these mutations prognostic value in a wide range of tumors. Furthermore, the review summarizes the recent findings pertaining to the FBXW7 and NOTCH interactome and its involvement in phosphorylation-related events, cell cycle, proliferation, apoptosis, and metastasis.
CONCLUSION: The review concludes by positioning FBXW7 as an effective diagnostic marker in tumors and by listing out recent advancements made in cancer therapeutics in identifying protocols targeting the FBXW7-NOTCH aberrations in tumors.
OBJECTIVE: To evaluate the inhibitory effects of PEITC against benzo[a]pyrene-induced rise in rat liver CYP1A1 mRNA and apoprotein levels.
MATERIALS AND METHODS: Precision cut rat liver slices were treated with benzo[a]pyrene at 1 and 5 μM in the presence of PEITC (1-25 μM) for 24 hours, followed by determination of CYP1A1 mRNA and apoprotein levels using quantitative polymerase chain reaction and immunoblotting.
RESULTS: Findings revealed that PEITC inhibited benzo[a]pyrene-induced rise in rat liver CYP1A1 mRNA in a dose-dependent manner as well as the apoprotein levels of CYP1A.
CONCLUSIONS: It was demonstrated that PEITC can directly inhibit the bioactivation of benzo[a]pyrene, indicating chemopreventive potential.