Is DNA ploidy related to smoking?

BACKGROUND: In the oral cavity, genomic instability is caused by long-term exposure to carcinogens. The aim of this study was to evaluate the relationship between smoking and DNA ploidy. METHODS: Cytological material was obtained from patients participating in the Outpatient Smoking Treatment Program of the Heart Institute (INCOR-HCFMUSP), and of the Discipline of Oral Medicine (ICT-UNESP). The inclusion criteria for all groups were the absence of a history of malignant tumors, absence of clinical signs of changes in the selected area, and alcohol consumption of less than 3 units per week. Group 1:30 smokers before smoking cessation treatment; Group 2:30 non-smokers; Group 3:30 ex-smokers abstinent for at least 1 year. Cytological smears were collected from the floor of the mouth and border of the tongue and stained by Feulgen. Aneuploidy was evaluated using the ACIS® III system. RESULTS: The Kruskal-Wallis test showed no statistically significant difference (P = .4383) between the groups studied. No association between tobacco consumption and aneuploidy was observed in group 1 (P = 1) or group 2 (P = .68; Fisher's exact test). CONCLUSION: Smoking was not associated with changes in DNA content or the incidence of aneuploidy in normal oral mucosa.

Cortical microarchitecture and remodeling-associated gene expression related to oral cancer prognosis.

The objective of this study was to assess the remodeling-associated gene expression in the mandible of patients diagnosed with oral squamous cell carcinoma (OSCC), investigating the cortical microarchitecture, and their influence on disease-free survival (DFS) and overall survival (OS) rates. A total of twenty-four patients who underwent mandibulectomy for OSCC treatment had two bone fragments harvested from the mandible for gene expression (RANK, RANKL, OPG, and SOST), and microarchitecture analysis, including bone volume, surface, mineral density, degree of anisotropy, and fractal dimension. The prognosis of the patients was assessed. The results revealed that RANK, RANKL, and SOST were predominantly downregulated, while OPG was completely downregulated. Tumors located adjacent to the posterior region of the mandible (p = 0.02), with a bone mineral density below 1.03 g/cm3 HA (p = 0.001), and a bone volume less than 86.47% (p = 0.03) were associated with poor outcomes. In conclusion, bone-remodeling-associated genes exhibited downregulation in the cortex of the mandible in OSCC patients. Additionally, the tumor's location within the mandible, bone volume, and cortical bone mineral density were identified as factors impacting DFS.

Relevant proteins for the monitoring of engraftment phases after allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Hematopoietic Stem Cell Transplant (HSCT) has been successfully used as standard therapy for hematological disorders. After conditioning therapy, patients undergoing allogeneic HSCT, present three different phases of engraftment: early pre-engraftment, early post-engraftment, and late engraftment. Severe complications are associated with morbidity, mortality, and malignancies in these phases, which include effects on the oral cavity. OBJECTIVES: The changes in the salivary composition after HSCT may contribute to identifying relevant proteins that could map differences among the phases of diseases, driven for personalized diagnostics and therapy. METHODS: Unstimulated whole saliva was collected from patients submitted to HSCT. The samples were submitted to trypsin digestion for a Mass spectrometry analysis. MaxQuant processed the Data analysis, and the relevant expressed proteins were subjected to pathway and network analyses. RESULTS: Differences were observed in the most identified proteins, specifically in proteins involved with the regulation of body fluid levels and the mucosal immune response. The heatmap showed a list of proteins exclusively expressed during the different phases of HSCT: HBB, KNG1, HSPA, FGB, APOA1, PFN1, PRTN3, TMSB4X, YWHAZ, CAP1, ACTN1, CLU and ALDOA. Bioinformatics analysis implicated pathways involved in protein processing in the endoplasmic reticulum, complement and coagulation cascades, apoptosis signaling, and cholesterol metabolism. CONCLUSION: The compositional changes in saliva reflected the three phases of HSCT and demonstrated the usefulness of proteomics and computational approaches as a revolutionary field in diagnostic methods.

Expression of Bcl-2 family proteins and association with clinicopathological characteristics of oral squamous cell carcinoma.

AIMS: To characterize the expression of proteins that inhibit (Bcl-2, Bcl-x, Bcl-xL, Bcl-2-related protein A1, BAG-1) or promote (Bak, Bax, Bim/Bod, Bim-Long, Bad, Bid, PUMA) apoptosis and determine possible correlations between the expression of these proteins and clinicopathological features of oral squamous cell carcinoma (OSCC). METHODS AND RESULTS: Two-hundred and twenty-nine cases of OSCC, arranged in a tissue microarray, were immunohistochemically analysed. The results demonstrated that the absence of vascular invasion was associated with increased expression of Bak, Bax, Bcl-xL, Bcl-2-related protein and PUMA. Increased expression of Bim/Bod and BAG-1 was associated with the presence of perineural infiltration. An increase in Bid and Bim-Long expression was associated with moderately to well-differentiated tumours. Increased expression of the Bcl-2-related protein and PUMA was associated with tumours occurring in the floor of mouth and increased expression of PUMA was also associated with recurrence of the tumour. Multivariate Cox analysis demonstrated that PUMA and Bim-Long were independent factors in prognosis of OSCC. CONCLUSIONS: Our results showed the involvement of the Bcl-2 family of proteins in OSCC tumorigenesis and suggest that the expression of apoptotic molecules might be used as a prognostic indicator for OSCC.

Cortical microarchitecture and remodeling-associated gene expression related to oral cancer prognosis

Abstract The objective of this study was to assess the remodeling-associated gene expression in the mandible of patients diagnosed with oral squamous cell carcinoma (OSCC), investigating the cortical microarchitecture, and their influence on disease-free survival (DFS) and overall survival (OS) rates. A total of twenty-four patients who underwent mandibulectomy for OSCC treatment had two bone fragments harvested from the mandible for gene expression (RANK, RANKL, OPG, and SOST), and microarchitecture analysis, including bone volume, surface, mineral density, degree of anisotropy, and fractal dimension. The prognosis of the patients was assessed. The results revealed that RANK, RANKL, and SOST were predominantly downregulated, while OPG was completely downregulated. Tumors located adjacent to the posterior region of the mandible (p = 0.02), with a bone mineral density below 1.03 g/cm3 HA (p = 0.001), and a bone volume less than 86.47% (p = 0.03) were associated with poor outcomes. In conclusion, bone-remodeling-associated genes exhibited downregulation in the cortex of the mandible in OSCC patients. Additionally, the tumor's location within the mandible, bone volume, and cortical bone mineral density were identified as factors impacting DFS.

Does elective neck dissection in T1/T2 carcinoma of the oral tongue and floor of the mouth influence recurrence and survival rates?

The aim of this study was to evaluate the results of elective neck dissection compared with observation (control group) in selected cases of early carcinoma of the oral tongue and floor of the mouth. It was a retrospective analysis of 222 patients who had the tumour resected (161 also had elective neck dissection). Occult lymph node metastases were detected in 33/161 (21%), and neck recurrences were diagnosed in 10 of the 61 patients in the control group (16%). Occult lymph node metastases reduced the 5-year disease-specific survival from 90% to 65% (p=0.001) and it was 96% among the controls. The 5-year disease-specific survival was 85% in the group treated by neck dissection and 96% in the observation group (p=0.09). Rigorous follow-up of selected low risk patients is associated with high rates of salvage, and overall survival was similar to the observed survival in patients treated by elective neck dissection. Observation is a reasonable option in the treatment of selected patients.

Nucleophosmin, p53, and Ki-67 expression patterns on an oral squamous cell carcinoma tissue microarray.

Oral cancer is the eighth most prevalent cancer worldwide. It causes significant mortality and morbidity rates, which have motivated the search for prognostic factors to better tailor the individual management of oral squamous cell carcinoma patients. Nucleophosmin is a multifunctional protein that is involved in many cellular activities, such as, regulation of the tumor suppressor genes TP53 and p14(ARF) and is associated with proliferative and growth suppressive roles in the cell. Nucleophosmin is overexpressed in many solid tumors in human, including tumors of the colon, liver, stomach, ovary, and prostate. In this study, we analyzed the expression of nucleophosmin, Ki-67, and p53 by immunohistochemistry in oral squamous cell carcinomas. Less than 10% of nuclear staining was observed in 90.3%, 50.6%, and 65.3% of the cases for nucleophosmin, p53, and Ki-67, respectively. Expression of p53 was not significantly associated with any of the clinicopathologic parameters analyzed. Increased expression of Ki-67 was associated with the presence of lymph node metastasis (P < .0001), advanced stages of disease (P = .0030), tumors occurring in the floor of mouth (P = .0018), and moderately/well-differentiated tumors (P = .0287). Local recurrence was associated with higher expression of nucleophosmin (P = .0233), and disease-free survival rate was significantly better in patients with low expression of nucleophosmin. Multivariate analysis suggested that expression of nucleophosmin could be an independent prognostic factor for oral squamous cell carcinoma patients.