4-Nitroquinoline-1-oxide induced experimental oral carcinogenesis

Kanojia, Deepak; Vaidya, Milind M.

doi:10.1016/j.oraloncology.2005.10.013

Cited by 240 publications

(243 citation statements)

References 81 publications

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“…The current study tested the immunological and clinical effects of PD‐1 blocking antibody treatment in a mouse 4NQO carcinogen‐induced premalignant oral lesion model that progresses to oral cancer. This model represents the stages of carcinogenesis‐induced cancer described for tobacco products 41. In addition, similar to what has been shown for human subjects with premalignant lesions, we had previously shown that mice bearing 4NQO‐induced premalignant oral lesions have increased expression of PD‐1 on their CD4 + and CD8 + T‐cells 8.…”

Section: Discussionsupporting

confidence: 67%

Transient immunological and clinical effectiveness of treating mice bearing premalignant oral lesions with PD‐1 antibodies

Levingston

Young

2017

Intl Journal of Cancer

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A carcinogen‐induced premalignant oral lesion model that progresses to oral cancer was used to examine the impact of blocking PD‐1 on cytokine expression and on progression of lesions to cancer. The results of this study show increased production of IL‐2 and the inflammatory cytokines IL‐6, IL‐17 and TNF‐α by spleen cells of lesion‐bearing mice that were treated with PD‐1 antibody for 1 week compared to cytokine production by spleen cells of lesion‐bearing mice treated with control antibody. Production of IFN‐γ increased at 3 weeks of PD‐1 antibody treatment, although production of the other Th1 and inflammatory mediators declined. By 5 weeks, levels of these cytokines declined for both control and PD‐1 antibody‐treated mice. Flow cytometric analysis for IFN‐γ‐expressing cells showed shifts in CD4+ cells expressing IFN‐γ consistent with the changes in cytokine secretion. Whether or not treatment generated reactivity to lesions or HNSCC was determined. Spleen cells from PD‐1 antibody‐treated mice were stimulated by lysates of premalignant lesion and HNSCC tongue tissues to produce increased levels of Th1 and select inflammatory cytokines early in the course of PD‐1 antibody treatment. However, with continued treatment, reactivity to lesion and HNSCC lysates declined. Analysis of clinical response to treatment suggested an early delay in lesion progression but, with continued treatment, lesions in PD‐1 antibody‐treated mice progressed to the same degree as in control antibody‐treated mice. Overall, these results show an early beneficial response to PD‐1 antibody treatment, which then fails with continued treatment and lesion progression.

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Section: Discussionsupporting

confidence: 67%

Transient immunological and clinical effectiveness of treating mice bearing premalignant oral lesions with PD‐1 antibodies

Levingston

Young

2017

Intl Journal of Cancer

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“…47 Among them, the 4-NQO-induced oral cancer mouse model is one of the most widely used, 24,25,47,48 as it recapitulates many features observed in human OSCC development including molecular expression of keratin, p16, and epidermal growth factor receptor (EGFR) which are associated with human oral carcinogenesis. Therefore, this model is suitable for the analysis of the OCC development in various mutant and transgenic strains.…”

Section: Discussionmentioning

confidence: 99%

CD24 blunts oral squamous cancer development and dampens the functional expansion of myeloid-derived suppressor cells

et al. 2016

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CD24 expression has been implicated in the oncogenesis of multiple types of cancer and high tumor expression is considered a poor prognosis factor; however, the role of CD24 in oral cancer progression is unknown. Unlike other cancer types, we found that higher CD24 levels in human oral cancers are correlated to lower clinical stage and better overall survival. We then dissected the role of CD24 and mechanisms in oral cancer pathogenesis in mice using a genetic strategy and demonstrated that CD24 deficiency increased the oral cavity tumor burden in response to the carcinogen 4-nitroquioline 1-oxide (4-NQO). Immune profile analysis showed a significant expansion as well as increased suppressive function of myeloid-derived suppressor cells (MDSCs) in CD24 ¡/¡ mice, but no apparent impairment in T cells, B cells, or dendritic cells. Further, studies with an orthotopically transplanted syngeneic squamous carcinoma model in the tongue of CD24 ¡/¡ and CD24 C/¡ mice confirmed the protective roles of CD24 against cancer. Moreover, the difference in tumor growth between CD24 ¡/¡ and CD24 C/¡ mice was blunted by immunodepletion of MDSCs. We conclude that CD24 expression impedes MDSC expansion and function, and thus slows oral cancer oncogenesis. This study is the first to examine the role of CD24 in a de novo oral cancer model, and it highlights the need to consider the immune regulatory roles of CD24 in the development of CD24-targeted therapy for cancer.

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“…Although 9,10-dimethyl-1,2-benzanthracene remains one of the most widely used chemical carcinogens, it is a potent irritant and may have limited use in studying early HNSCC lesions because it produces an inflammatory response, necrosis, and the appearance of granulation tissue when applied locally in the oral cavity (see ref. 9 and references therein). Addressing this limitation, early work revealed that the synthetic water-soluble chemical carcinogen 4-nitroquinoline-1 oxide (4NQO) is more effective for inducing oral carcinogenesis in rats compared with 9,10-dimethyl-1,2-benzanthracene and does not cause an extensive inflammatory response (see ref.…”

mentioning

confidence: 99%

“…Addressing this limitation, early work revealed that the synthetic water-soluble chemical carcinogen 4-nitroquinoline-1 oxide (4NQO) is more effective for inducing oral carcinogenesis in rats compared with 9,10-dimethyl-1,2-benzanthracene and does not cause an extensive inflammatory response (see ref. 9 and references therein). Therefore, 4NQO was adapted as early as in the mid-1960s for the development of oral squamous cell carcinoma (SCC) in mice, the experimental animal most frequently used for carcinogenesis studies.…”

mentioning

confidence: 99%

“…4NQO forms DNA adducts, causes adenosine for guanosine substitutions, and induces intracellular oxidative stress resulting in mutations and DNA strand breaks, all similar to the genetic alterations provoked by tobacco carcinogens, and so 4NQO serves as a surrogate for tobacco exposure (9,38,39). Oral-specific carcinogenesis can be achieved by the local delivery of this carcinogen, most often by laborintensive procedures including brushing the hard palate, tongue, or gingiva with concentrated water solutions of 4NQO, which leads to the progressive acquisition of oral premalignant lesions and SCC (Table 1).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Chemical Carcinogenesis Models for Evaluating Molecular-Targeted Prevention and Treatment of Oral Cancer

Vitale‐Cross

Czerninski

Amornphimoltham

et al. 2009

Cancer Prevention Research

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4-Nitroquinoline-1-oxide induced experimental oral carcinogenesis

Cited by 240 publications

References 81 publications

Transient immunological and clinical effectiveness of treating mice bearing premalignant oral lesions with PD‐1 antibodies

Transient immunological and clinical effectiveness of treating mice bearing premalignant oral lesions with PD‐1 antibodies

CD24 blunts oral squamous cancer development and dampens the functional expansion of myeloid-derived suppressor cells

Chemical Carcinogenesis Models for Evaluating Molecular-Targeted Prevention and Treatment of Oral Cancer

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