4NQO Carcinogenesis: A Model of Oral Squamous Cell Carcinoma

Rivera, César

doi:10.4067/s0717-95022012000100055

Cited by 15 publications

(3 citation statements)

References 33 publications

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“…All carcinogenesis evolves from initial cell injury to the formation of a malignant neoplasm (Hanahan, Weinberg, 2011). Histologically, the lesion passes from reactive epithelial changes (such as hyperkeratosis, hyperplasia and acanthosis) or pre-neoplastic changes (including mild, moderate and severe dysplasia) prior to the establishment of an invasive carcinoma (Neville et al, 2009;Rivera, 2012). In a case-control study, Minhas et al (2021) have reported that cytological changes were observed not only in neoplastic epithelial cells but the nonneoplastic epithelial cells are also affected, resulting in cytopathological atypical changes in patients receiving concomitant chemoradiotherapy (CCRT) as a treatment for oral squamous cell carcinoma (OSCC), Nuclear atypia features were higher on the 17th day and end of treatment; whereas, epithelial atypia was mainly observed on the 17th day of CCRT (40 %).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Cytopathology of Human Buccal Mucosa Neoplasm

2023

European Journal of Medicine

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The objective of the present study is to investigate the frequency of pleomorphic cytological atypias in the exfoliated cytosmears of human buccal mucosa neoplasms (HBMN), pattern of cervical lymph node (CLN) metastasis and to establish its role as a diagnostic criterion for early detection of oral cancer.In a hospital-based case-control study, a total of 126 subjects (63 HBMN cases and 63 healthy individuals) were included. Two scalpel-scraped exfoliated cytosmears were collected from the affected site of the buccal mucosa and were fixed in aceto-alcohol (1:3) immediately. Cytosmears were stained with Papanicolaou's stain and Giemsa's stain. Cat Cam 1.30 (1.3 Mega Pixel) microscope camera was used for phptomicrography. Software package Palaeontological Statistics (PAST) ®, Version 2.17 was used for statistical analysis.Cytological pleomorphism was well observed exhibiting a number atypias in the exfoliated cytosmears of HBMN. The frequencies of typically atypical cells like KSC, KTC, KSC-A, KFC, KRC, PKSC, MNC and NMSCs are observed to be directly correlated with the degree of pathogenicity at different stages of oral carcinogenesis. Diagnostically, the Sensitivity was calculated to be 93.1 % and Specificity was 100 %, Positive Predictive Value (PPV) was 100 %, Negative Predictive Value (NPV) was 55.6 % and the accuracy was 93.7 %.Presence of any such cytological atypias in the exfoliated cytosmears of HBMN indicates the state of malignancy and thus, the finding is practically helpful in determining the stage of the HBMN. However, the role of tobacco and alcohol in connection to unusual CLN metastasis with particular reference to the HBMN needs further research.

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Section: Discussionmentioning

confidence: 99%

Diagnostic Cytopathology of Human Buccal Mucosa Neoplasm

2023

European Journal of Medicine

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“…The selection of a mouse model was due to its ability to form all phases of OSCC (dysplasia, carcinoma in situ, and OSSC with its different grades) and its sensitivity to demonstrating the effects of anti-cancer treatments 39 , 40 . Carcinogenesis is a long multistage process in which invasion was induced after several months but it is proven by some studies that it was hard to induce OSCC with other chemicals 41 – 43 . Punch biopsies confirmed the formation of different stages of OSCC 44 .…”

Section: Discussionmentioning

confidence: 99%

A novel intra-tumoral drug delivery carrier for treatment of oral squamous cell carcinoma

Elsaady,

Aboushelib,

Al-Wakeel

et al. 2023

Sci Rep

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The treatment of oral squamous cell carcinoma (OSCC) includes systemic chemotherapy and is associated with aggressive side effects on patients. This study evaluated a new intra-tumor-targeted drug delivery method for the treatment of OSCC induced on the dorsum of the tongue in white mice. The induced tumors were examined by needle biopsy. A targeted anticancer drug (Cetuximab) and [Cisplatin and 5 Fluorouracil (5-FU)] chemotherapeutic agents were loaded on polyethylene glycol-polylactide-polyethylene glycol (PEG-PLA-PEG) nanoparticles (NPs) designed for intralesional injection while systemic administration was used as control. Fourier transform infrared spectroscopy (FTIR) was performed to study NP chemical structure, a drug release profile was conducted to study release kinetics, and histopathological evaluation was performed before and after treatment to evaluate tissue reactions (n-28, ά = 0.05). The drug release profile was characteristic of the chemotherapeutic agent showing early quick ascend followed by sustained slow release. FTIR peaks identified the polymeric structure of the drug nano-carrier. Histopathologic examination of chemically induced OSCC revealed different grades ranging from non-invasive to invasive stages of OSCC. Intra-tumoral test group revealed significant remission of observed cancer grade compared to the systemically administered group (X2 = 12.63, P < 0.001). Finally, using synthesized PEG–PLA–PEG NPs for intralesional injection is a promising route for the treatment of OSCC.

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“…The most widely used model of induced experimental oral (tongue) carcinogenesis that may fulfill our requirement is the usage of 4-nitroquinoline-1-oxide or 4NQO (14,15). 4NQO is a synthetic water soluble carcinogen, causes several systemic and molecular damages by promoting DNA adduct formation and intracellular oxidative stress (16).…”

Section: Introductionmentioning

confidence: 99%

The immunomodulatory impact of naturally derived neem leaf glycoprotein on the initiation progression model of 4NQO induced murine oral carcinogenesis: a preclinical study

Das,

Bera,

Ganguly

et al. 2024

Front. Immunol.

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IntroductionMurine tumor growth restriction by neem leaf glycoprotein (NLGP) was established in various transplanted models of murine sarcoma, melanoma and carcinoma. However, the role of NLGP in the sequential carcinogenic steps has not been explored. Thus, tongue carcinogenesis in Swiss mice was induced by 4-nitroquinoline-1-oxide (4NQO), which has close resemblance to human carcinogenesis process. Interventional role of NLGP in initiation-promotion protocol established during 4NQO mediated tongue carcinogenesis in relation to systemic immune alteration and epithelial-mesenchymal transition (EMT) is investigated.Methods4NQO was painted on tongue of Swiss mice every third day at a dose of 25µl of 5mg/ml stock solution. After five consecutive treatment with 4NQO (starting Day7), one group of mice was treated with NLGP (s.c., 25µg/mice/week), keeping a group as PBS control. Mice were sacrificed in different time-intervals to harvest tongues and studied using histology, immunohistochemistry, flow-cytometry and RT-PCR on different immune cells and EMT markers (e-cadherin, vimentin) to elucidate their phenotypic and secretory status.ResultsLocal administration of 4NQO for consecutive 300 days promotes significant alteration in tongue mucosa including erosion in papillae and migration of malignant epithelial cells to the underlying connective tissue stroma with the formation of cell nests (exophytic-hyperkeratosis with mild dysplasia). Therapeutic NLGP treatment delayed pre-neoplastic changes promoting normalization of mucosa by maintaining normal structure. Flow-cytometric evidences suggest that NLGP treatment upregulated CD8+, IFNγ+, granzyme B+, CD11c+ cells in comparison to 4NQO treated mice with a decrease in Ki67+ and CD4+FoxP3+ cells in NLGP treated cohort. RT-PCR demonstrated a marked reduction of MMP9, IL-6, IL-2, CD31 and an upregulation in CCR5 in tongues from 4NQO+NLGP treated mice in comparison to 4NQO treated group. Moreover, 4NQO mediated changes were associated with reduction of e-cadherin and simultaneous up-regulation of vimentin expression in epithelium that was partially reversed by NLGP.DiscussionEfficacy of NLGP was tested first time in sequential carcinogenesis model and proved effective in delaying the initial progression. NLGP normalizes type 1 immunity including activation of the CD8+T effector functions, reduction of regulatory T cell functions, along with changes in EMT to make the host systemically alert to combat the carcinogenic threat.

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4NQO Carcinogenesis: A Model of Oral Squamous Cell Carcinoma

Cited by 15 publications

References 33 publications

Diagnostic Cytopathology of Human Buccal Mucosa Neoplasm

Diagnostic Cytopathology of Human Buccal Mucosa Neoplasm

A novel intra-tumoral drug delivery carrier for treatment of oral squamous cell carcinoma

The immunomodulatory impact of naturally derived neem leaf glycoprotein on the initiation progression model of 4NQO induced murine oral carcinogenesis: a preclinical study

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