66 research outputs found

    Are There Betel Quid Mixtures Less Harmful than Others? A Scoping Review of the Association between Different Betel Quid Ingredients and the Risk of Oral Submucous Fibrosis

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    Oral submucous fibrosis (OSF) is a potentially malignant condition of the oral cavity characterized by progressive fibrosis of the submucosal tissues. OSF is typically associated with the use of betel quid (BQ), a chewing package made of natural products (e.g., areca nut, betel leaves), with or without smokeless tobacco. BQ ingredients contain pro-carcinogenic bioactive compounds, but also potentially protective biomolecules, and we have shown recently that the chemical properties of different BQ recipes vary, which may explain the unequal prevalence of OSF and oral cancer in BQ users in different geographical regions. Hence, this scoping review was aimed at evaluating the existing literature regarding different BQ compounds and their association with OSF. The repository of the National Library of Medicine (MEDLINE/PubMed), medRxiv databases, Google scholar, Baidu scholar, CNKI, and EBSCO were used to search for publications that investigated the association between BQ chewing and OSF up to November 2021. The search terminology was constructed using the keywords “betel quid” and “oral submucous fibrosis”, and their associated terms, with the use of Boolean operators. The search was conducted under Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, together with clear inclusion and exclusion criteria. The review showed that the risk of developing OSF varied between different BQ recipes, and that chewing BQ mixtures containing betel inflorescence (BI) significantly increased the risk of OSF, as did the addition of tobacco. Conversely, the use of betel leaf in the mixture was likely to be protective, which may be due to the presence of polyphenols. Although further research is needed to determine the effect of individual BQ ingredients in the development of OSF, our pilot results provide the scope and rationale for informing future chemopreventive strategies for OSF and oral cancer in BQ chewers

    Transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasia

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    Oral potentially malignant disorders (OPMD) are precursors of oral squamous cell carcinoma (OSCC), and the presence of oral epithelial dysplasia (OED) in OPMD confers an increased risk of malignant transformation. Emerging evidence has indicated a role for the immune system in OPMD disease progression; however, the underlying immune mechanisms remain elusive. In this study, we used immune signatures established from cancer to delineate the immune profiles of moderate and severe OED, which are considered high-risk OPMD. We demonstrated that moderate and severe OEDs exhibit high lymphocyte infiltration and upregulation of genes involved in both immune surveillance (major histocompatibility complex-I, T cells, B cells and cytolytic activity) and immune suppression (immune checkpoints, T regulatory cells, and tumor-associated macrophages). Notably, we identified three distinct subtypes of moderate and severe OED: immune cytotoxic, non-cytotoxic and non-immune reactive. Active immune surveillance is present in the immune cytotoxic subtype, whereas the non-cytotoxic subtype lacks CD8 immune cytotoxic response. The non-immune reactive subtype showed upregulation of genes involved in the stromal microenvironment and cell cycle. The lack of T cell infiltration and activation in the non-immune reactive subtype is due to the dysregulation of CTNNB1, PTEN and JAK2. This work suggests that moderate and severe OED that harbor the non-cytotoxic or non-immune reactive subtype are likely to progress to cancer. Overall, we showed that distinct immune responses are present in high-risk OPMD, and revealed targetable pathways that could lead to potential new approaches for non-surgical management of OED

    Time-to-Treatment of Oral Cancer and Potentially Malignant Oral Disorders: Findings in Malaysian Public Healthcare

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    This study aims to evaluate the time-to-treatment of oral cancer and potentially malignant oral disorders (PMOD) in a Malaysian public healthcare setting while exploring its contributing factors. It consists of (1) a cross-sectional patient survey to quantify time to seek care and barriers faced, and (2) a retrospective medical record abstraction to determine treatment and management intervals. Time intervals were aggregated and analyzed by their primary contributor—patient, professional, or healthcare system. The average total time-to-treatment of the 104 patients investigated was 167 days (SD = 158). This was predominantly contributed by the patient interval of 120 days (SD = 152). In total, 67.0% of patients delayed their visit to primary healthcare centers because they assumed the lesions were not dangerous or of concern. Additionally, there was a significant difference between patients ‘facing’ and ‘not facing’ difficulties to seek care, at 157 vs. 103 days (p = 0.028). System and professional delays were comparably shorter, at 33 days (SD = 20) and 10 days (SD = 15) respectively. Both demonstrated a significant difference between oral cancer and PMOD, at 43 vs. 29 days (p p < 0.001). The findings reiterate the need to reform current initiatives to better promote early lesion recognition by patients and implement strategies for the elimination of their access barriers

    The association of maternal gestational hyperglycemia with breastfeeding duration and markers of milk production

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    Background: previous studies focusing on the association between gestational diabetes and breastfeeding duration have been inconclusive.Objectives: we aimed to determine whether maternal gestational hyperglycemia is associated with the duration of breastfeeding and the concentrations of markers linked to breastmilk production.Methods: data from the prospective, multi-ethnic Growing Up in Singapore Towards healthy Outcomes (GUSTO) study was used to assess the association of fasting plasma glucose (FPG) and 2-hour post challenge glucose (2hPG) measured at 26-28 weeks’ gestation with duration of breastfeeding and concentrations of protein, lactose, citrate, sodium, potassium and zinc in breastmilk 3 weeks postpartum. Results: of the 1035 participants, 5.2% and 9.5% had elevated FPG and 2hPG, respectively, consistent with a diagnosis of gestational diabetes mellitus (GDM) based on International Association of Diabetes and Pregnancy Study Groups criteria. FPG ≥ 5.1 mmol/L was associated with a crude reduction in median breastfeeding duration of 2.3 months. In a model adjusted for maternal pre-pregnancy BMI and intention to breastfeed, FPG ≥ 5.1 mmol/L predicted earlier termination of any breastfeeding (Adjusted hazard ratio [95% CI]: 1.47 [1.04, 2.08]) but not full breastfeeding (1.08 [0.76, 1.55]). 2hPG ≥ 8.5 mmol/L was not significantly associated with the durations of any or of full breastfeeding (0.86 [0.62, 1.19] and 0.85 [0.62, 1.18], respectively). Maternal FPG was significantly and positively associated with breastmilk sodium and sodium-to-potassium (Na:K) ratio (Adjusted coefficient [95% CI]: 1.28 [1.08, 1.51] and 1.29 [1.08, 1.54], respectively), but not with other measured breastmilk components. Conclusions: women with FPG ≥ 5.1 mmol/L during pregnancy breastfeed for a shorter duration. Future work involving measurement of milk production is needed to determine whether low milk production predicts breastfeeding duration among women with elevated FPG.<br/

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

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    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

    DNA Vaccines Targeting Novel Cancer-Associated Antigens Frequently Expressed in Head and Neck Cancer Enhance the Efficacy of Checkpoint Inhibitor

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    HPV-independent head and neck squamous cell carcinoma (HNSCC) is a common cancer globally. The overall response rate to anti-PD1 checkpoint inhibitors (CPIs) in HNSCC is ~16%. One major factor influencing the effectiveness of CPI is the level of tumor infiltrating T cells (TILs). Converting TILlow tumors to TILhigh tumors is thus critical to improve clinical outcome. Here we describe a novel DNA vaccines to facilitate the T-cell infiltration and control tumor growth. We evaluated the expression of target antigens and their respective immunogenicity in HNSCC patients. The efficacy of DNA vaccines targeting two novel antigens were evaluated with or without CPI using a syngeneic model. Most HNSCC patients (43/44) co-expressed MAGED4B and FJX1 and their respective tetramer-specific T cells were in the range of 0.06-0.12%. In a preclinical model, antigen-specific T cells were induced by DNA vaccines and increased T cell infiltration into the tumor, but not MDSC or regulatory T cells. The vaccines inhibited tumor growth and improved the outcome alone and upon combination with anti-PD1 and resulted in tumor clearance in approximately 75% of mice. Pre-existence of MAGED4B and FJX1-reactive T cells in HNSCC patients suggests that these widely expressed antigens are highly immunogenic and could be further expanded by vaccination. The DNA vaccines targeting these antigens induced robust T cell responses and with the anti-PD1 antibody conferring excellent tumor control. This opens up an opportunity for combination immunotherapy that might benefit a wider population of HNSCC patients in an antigen-specific manner
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