preneoplasia

BACKGROUNDS: Microbiome dysbiosis is an important contributing factor in tumor development and thus may be a risk predictor for human malignancies. In the United States, women with Hispanic/Latina (HIS) and African American (AA) background have a higher incidence of cervical cancer and poorer outcomes than Caucasian American (CA) women. METHODS: Here, we assessed the distribution pattern of microbiota in cervical intraepithelial neoplasia (CIN) lesions obtained from HIS (n = 12), AA (n = 12), and CA (n = 12) women, who were screened for CC risk assessment...

The gallbladder undergoes different types of pathologies, ranging from inflammatory to preneoplasia and finally to malignant lesions. Gallbladder carcinoma can be highly invasive, and it is known that chronic inflammation of the gallbladder can lead to preneoplastic abnormalities and subsequently malignant phenotypes. Gallbladder neoplasia has a low incidence but is associated with a very poor prognosis. An early diagnosis is therefore extremely important in order to improve the prognosis of patients. Immunohistochemical markers of the mucin family can distinguish between different types of gallbladder lesions...

SOX2 expression in high-grade cervical intraepithelial neoplasia (CIN3) and cervical squamous cell carcinoma is increased compared to that in the normal cervical epithelium. However, data on the expression and histological distribution of SOX2 in squamous epithelium during progression of CIN are largely lacking. We studied SOX2 expression throughout the epithelium in 53 cases of CIN1, 2, and 3. In general, SOX2 expression increased and expanded from basal/parabasal to the intermediate/superficial compartment during early stages of progression of CIN...

In the therapeutic domain, targeted therapies have been shown to be generally more effective when given to patients with tumors that harbor the targeted aberration. This principle has not been tested in cancer prevention despite evidence that molecular heterogeneity accompanies the multi-step progression to invasive disease. We hypothesized that efficacy of agents targeting the precancerous state varies based on timing of the treatment relative to the underlying molecular changes. MCF10A cell line-based model of the multi-step progression to TNBC was used...

Recent advances in bulk sequencing approaches as well as genomic decoding at the single-cell level have revealed surprisingly high somatic mutational burdens in normal tissues, as well as increased our understanding of the landscape of "field cancerization", that is, molecular and immune alterations in mutagen-exposed normal-appearing tissues that recapitulated those present in tumors. Charting the somatic mutational landscapes in normal tissues can have strong implications on our understanding of how tumors arise from mutagenized epithelium...

OBJECTIVE: To use large-scale electronic health record (EHR) data to develop machine learning models predicting malignant transformation of oral lesions. METHODS: A multi-institutional health system database was used to identify a retrospective cohort of patients with biopsied oral lesions. The primary outcome was malignant transformation. Chart review and automated system database queries were used to identify a range of demographic, clinical, and pathologic variables...

BACKGROUND AND AIMS: Mesenchymal-epithelial crosstalk (MEC) in the stomach is executed by pathways such as bone morphogenetic protein (BMP) and extracellular signal-regulated kinase (ERK). Mis-regulation of MEC disrupts gastric homeostasis and causes tumorigenesis. Protein Kinase A (PKA) crosstalks with BMP and ERK signaling; however, PKA function(s) in stomach development and homeostasis remains undefined. METHODS: We generated a novel Six2-Cre+/- PKAcαRfl/wt (CA-PKA) mouse in which expression of constitutive-active PKAcαR was induced in gastric mesenchyme progenitors...

Spontaneous mouse models of medulloblastoma (MB) offer a tractable system to study malignant progression in the brain. Mouse Sonic Hedgehog (Shh)-MB tumours first appear at postnatal stages as preneoplastic changes on the surface of the cerebellum, the external granule layer (EGL). Here we compared traditional histology and 3DISCO tissue clearing in combination with light sheet fluorescence microscopy (LSFM) to identify and quantify preneoplastic changes induced by disrupting stromal Norrin/Frizzled 4 (Fzd4) signalling, a potent tumour inhibitory signal in two mouse models of spontaneous Shh-MB...

Oral potentially malignant disorders (OPMD) may precede oral squamous cell carcinoma (OSCC). Reported rates of malignant transformation of OPMD range from 3 to 50%. While some clinical, histological, and molecular factors have been associated with a high-risk OPMD, they are, to date, insufficiently accurate for treatment decision-making. Moreover, this range highlights differences in the clinical definition of OPMD, variation in follow-up periods, and molecular and biological heterogeneity of OPMD. Finally, while treatment of OPMD may improve outcome, standard therapy has been shown to be ineffective to prevent OSCC development in patients with OPMD...

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is recognized as a main mediator bridging innate and adaptive immunity, recent advances have expanded its roles to anti-tumor immunity and carcinogenesis. Loss of cGAS-STING signaling in non-small cell lung cancer (NSCLC) leads to enhanced tumorigenicity and decreased cytotoxic T lymphocyte infiltration. Apart from its anticancer response, persistent overreaction of cGAS-STING signaling promotes progression of certain inflammation-aggravated cancers...

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) requires new treatments and targeted approaches to improve survival. The peroxisome proliferator-activated receptor γ (PPARγ) and retinoic X receptor alpha (RXRα) nuclear receptor pathways may be targetable with repurposed Food and Drug Administration (FDA)-approved agents for prevention and treatment. METHODS: Oral cancer and leukoplakia cell lines were treated with the PPARγ agonist (pioglitazone) and RXRα activator (bexarotene)...

Background: Hypergastrinaemia occasionally indicates the presence of a gastrinoma. However it is much more commonly associated with various benign causes including proton pump inhibitor (PPI) use, Helicobacter pylori infection and/or atrophic gastritis. The extent to which these factors interact to influence fasting serum gastrin concentrations remains incompletely understood. Materials and Methods: Fasting serum gastrin concentrations were measured by radioimmunoassay in 1,400 patients attending for diagnostic oesophagogastro-duodenoscopy...

Metabolic reprogramming evolves during cancer initiation and progression. However, thorough understanding of metabolic evolution from preneoplasia to lung adenocarcinoma (LUAD) is still limited. Here, we perform large-scale targeted metabolomics on resected lesions and plasma obtained from invasive LUAD and its precursors, and decipher the metabolic trajectories from atypical adenomatous hyperplasia (AAH) to adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC), revealing that perturbed metabolic pathways emerge early in premalignant lesions...

PURPOSE: Oral cancers lack standardized monitoring systems. Our institution has developed an active surveillance system which provides detailed monitoring and follow up of patients with oral preneoplastic lesions (OPL). We examined a historic cohort of patients with OPL seen by regional dental professionals and a current cohort of clinic patients. The major aim was to examine follow up practices for biopsy proven dysplasia to gauge appropriateness of an active monitoring system for oral carcinoma...

The early diagnosis and management of oral potentially malignant disorders (OPMD) represent a unique opportunity to develop strategies that will prevent malignant transformation. Despite a high prevalence, awareness remains low, patient outcomes poor, and quality of life highly affected. How can patient advocacy groups (PAGs) bring more awareness to preneoplasia preceding oral cancers and help patients after the identification of a suspicious oral leukoplakia presented as white patches in the mouth? PAGs are today involved with awareness campaigns, lobbying, and education of both health care systems as well as the survivor and the newly diagnosed...

OBJECTIVE: We desired to establish an active surveillance clinic for head and neck cancer. In this review we examined. METHODS: We examined the natural history of human oral carcinogenesis, the types of preneoplastic lesions, and efforts at oral chemoprevention over the past decades for presentation here. RESULTS: We established a clinic and program for patients with oral premalignant lesions approximately over 15 years ago based on an unmetneed for this service...

Background: Human papillomavirus (HPV) infection is considered as the most common viral sexually transmitted infection worldwide. This poses an increasingly interdisciplinary medical challenge. Since there is vast scattered information in databases about HPV and the correlated diseases, we decided to collect useful data so that the experts can get a more comprehensive view of HPV. Methods: In this article, HPV-associated diseases, prevalence, prevention, and new treatments are discussed. The retrieved articles reporting the latest data about the required information for our review were selected through searching in Web of Science, Scopus, Medline (PubMed), EMBASE, Cochrane Library, Ovid, and CINHAL with language limitations of English and German...

Pterygium is a multifaceted pathology that displays apparent conflicting characteristics: benign (e.g., self-limiting and superficial), bad (e.g., proliferative and potentially recurrent) and ugly (e.g., signs of preneoplastic transformation). The natural successive question is: why are we lacking reports showing that pterygium lesions become life-threatening through metastasis, especially since pterygium has considerable similarities with UV-related malignancies on the molecular level? In this review, we consider how our pathophysiological understanding of the benign pterygium pathology overlaps with ocular surface squamous neoplasia and skin cancer...

Approximately 165,000 and 311,000 individuals die annually from urothelial (UC) and cervical (CC) cancer. The therapeutic success of these cancers depends strongly on their early detection and could be improved by use of additional diagnostic tools. We evaluated the current knowledge of the use of micronucleus (MN) assays (which detect structural and numerical chromosomal aberrations) with urine- (UDC) and cervix-derived (CDC) cells for the identification of humans with increased risks and for the diagnosis of UC and CC...

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