HPV16 induces a wasting syndrome in transgenic mice: Amelioration by dietary polyphenols via NF-κB inhibition

Costa, Rui M. Gil da; Aragão, S.; Moutinho, Magda S S; Alvarado, Antonieta; Carmo, Diogo Oliveira; Casaca, Fátima; Silva, Sandra; Ribeiro, Joana; Sousa, Hugo; Ferreira, Rita; Nogueira-Ferreira, Rita; Pires, Maria dos Anjos; Colaço, Bruno; Medeiros, Rui; Venâncio, Carlos; Oliveira, Maria Manuel; Bastos, Margarida; Lopes, Carlos; Oliveira, Paula A.

doi:10.1016/j.lfs.2016.10.031

Cited by 45 publications

(58 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the grip strength test, transgenic animals showed significantly lower values for maximum strength than their wild‐type counterparts, along with reduced bodyweight. This agrees with recent results from our group, showing that K14‐HPV16 mice develop severe systemic inflammation and muscle wasting, in connection with upregulation of NF‐κB subunits in skeletal muscle tissue, and that these effects are ameliorated by dietary polyphenols with NF‐κB inhibitory activity (Gil da Costa et al, ). In line with these findings, DMAPT was able to partially preserve bodyweight and maximum muscle strength on the treated group.…”

Section: Discussionsupporting

confidence: 93%

“…In this study, DMAPT also partially prevented a wasting syndrome typically observed in this mouse strain (Gil da Costa et al, 2017), in line with previous observations from a different group, using a mouse mammary cancer model (Wang et al, 2017).…”

Section: Dmapt Partly Prevents Wasting Syndrome In Hpv16 +/− Micesupporting

confidence: 92%

“…In fact, HPV oncoproteins are known to upregulate NF‐κB signaling during tumor progression as previously reviewed (Gil da Costa et al, ; Xu et al, ). Multiple anti‐inflammatory compounds have shown chemopreventive activity against HPV‐induced lesions in this model (Gil da Costa et al, ; Santos et al, ).…”

Section: Discussionmentioning

confidence: 98%

“…Our group and others recently characterized K14-HPV16 transgenic mice as a model to study HPV-driven carcinogenesis (Arbeit et al, 1994;Gil da Costa et al, 2017;Paiva et al, 2015a;Paiva et al, 2015b). Santos et al, 2016).…”

Section: Dmapt Partly Prevents Wasting Syndrome In Hpv16 +/− Micementioning

confidence: 99%

See 3 more Smart Citations

Dimethylaminoparthenolide reduces the incidence of dysplasia and ameliorates a wasting syndrome in HPV16‐transgenic mice

Santos

Moreira‐Pais

Neto

et al. 2019

Drug Development Research

Self Cite

View full text Add to dashboard Cite

The nuclear factor kappa light chain enhancer of activated B cells (NF‐κB) has been implicated in the progression of cancers induced by high‐risk human papillomaviruses (HPV). In cancer patients, NF‐κB is also thought to drive a chronic systemic inflammatory status, leading to cachexia. This study addressed the ability of dimethylaminoparthenolide (DMAPT), a water‐soluble NF‐κB inhibitor, to block the development of HPV‐induced lesions and wasting syndrome in HPV16‐transgenic mice. Mice received DMAPT orally (100 mg/kg/day), once a day, for 6 consecutive weeks. Body weight was monitored weekly along with food and water intake. After 6 weeks the animals were submitted to a grip strength test and sacrificed for specimen collection. Skin samples were analyzed histologically and for expression of NF‐κB‐regulated genes Bcl2 and Bcl2l1. Gastrocnemius muscles were weighted and analyzed for expression of NF‐κB subunits p50, p52, p65, and Rel‐B. DMAPT reduced the incidence of epidermal dysplasia (18.2% versus 33.3% in HPV16+/− untreated mice). This was associated with reduced expression of Bcl2 and Bcl2l1 (p = .0003 and p = .0014, respectively) and reduced neutrophilic infiltration (p = .0339). Treated mice also showed partially preserved bodyweight and strength, which were independent of the expression levels of NF‐κB subunits in skeletal muscle.These results suggest that NF‐κB inhibition may be a valid strategy against HPV‐induced lesions in vivo and warrant further preclinical tests particularly in the set of combination therapies. In addition, the data may support the use of DMAPT to prevent wasting syndrome.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Dmapt Partly Prevents Wasting Syndrome In Hpv16 +/− Micesupporting

confidence: 92%

Section: Discussionmentioning

confidence: 98%

Section: Dmapt Partly Prevents Wasting Syndrome In Hpv16 +/− Micementioning

confidence: 99%

See 2 more Smart Citations

Dimethylaminoparthenolide reduces the incidence of dysplasia and ameliorates a wasting syndrome in HPV16‐transgenic mice

Santos

Moreira‐Pais

Neto

et al. 2019

Drug Development Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…In cervical and also penile cancer, NF‐κB expression was elevated and is thought to contribute in the development of chronic inflammation towards cancer . In a recent study, it was shown that NF‐κB inhibitors are beneficial in the treatment of HPV16‐induced wasting syndrome in mice . These data all show that HPV effectively blocks viral recognition.…”

Section: Protein Function/traffickingmentioning

confidence: 99%

Immune evasion mechanisms of human papillomavirus: An update

Steinbach

Riemer

2017

Intl Journal of Cancer

108

107

View full text Add to dashboard Cite

Human papillomavirus (HPV) is the most frequently sexually transmitted agent in the world. It can cause cervical and other anogenital malignancies, and oropharyngeal cancer. HPV has the unique ability to persist in the host's epithelium for a long time-longer than most viruses do-which is necessary to complete its replication cycle. To this end, HPV has developed a variety of immune evasion mechanisms, which unfortunately also favor the progression of the disease from infection to chronic dysplasia and eventually to cancer. This article summarizes the current knowledge about HPV immune evasion strategies. A special emphasis lies in HPV-mediated changes of the antigen processing machinery, which is generating epitopes for T cells and contributes to the detectability of infected cells.

show abstract

HPV16 is sufficient to induce squamous cell carcinoma specifically in the tongue base in transgenic mice

Mestre

Medeiros‐Fonseca

Estêvão

et al. 2020

The Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Head and neck squamous cell carcinomas (HNSCCs) associated with human papillomavirus (HPV) occur specifically in the tonsils and the tongue base, but the reasons for this specificity remain unknown. We studied the distribution of oral and pharyngeal lesions in HPV16-transgenic mice where the expression of all the HPV16 early genes is targeted to keratinising squamous epithelia by the cytokeratin 14 (Krt14) gene promoter. At 30 weeks of age, 100% of mice developed low-and high-grade intraepithelial dysplasia at multiple sites. Twenty per cent of animals developed invasive cancers that remarkably were restricted to the tongue base, in association with the circumvallate papilla. The lesions maintained expression of CK14 (KRT14) and the HPV16 E6 and E7 oncogenes, and displayed deregulated cell proliferation and up-regulation of p16 INK4A . Malignant lesions were poorly differentiated and destroyed the tongue musculature. We hypothesised that the tongue base area might contain a transformation zone similar to those observed in the cervix and anus, explaining why HPV-positive cancers target that area specifically. Immunohistochemistry for two transformation zone markers, CK7 (KRT7) and p63 (TP63), revealed a squamocolumnar junction in the terminal duct of von Ebner's gland, composed of CK7 + luminal cells and p63 + basal cells. Dysplastic and invasive lesions retained diffuse p63 expression but only scattered positivity for CK7. Site-specific HPV-induced carcinogenesis in the tongue base may be explained by the presence of a transformation zone in the circumvallate papilla. This mouse model reproduces key morphological and molecular features of HPV-positive HNSCC, providing a unique in vivo tool for basic and translational research.No conflicts of interest were declared. or HPV18, are associated with HNSCC cases occurring at specific oropharyngeal sitesthe tonsils and the tongue base. This site specificity of HPV-positive lesions suggests the presence of HPV-sensitive transformation zones, such as those described in the uterine cervix and the anus [2,3]. However, those areas, if they indeed exist, Journal of Pathology

show abstract

HPV16 induces a wasting syndrome in transgenic mice: Amelioration by dietary polyphenols via NF-κB inhibition

Cited by 45 publications

References 31 publications

Dimethylaminoparthenolide reduces the incidence of dysplasia and ameliorates a wasting syndrome in HPV16‐transgenic mice

Dimethylaminoparthenolide reduces the incidence of dysplasia and ameliorates a wasting syndrome in HPV16‐transgenic mice

Immune evasion mechanisms of human papillomavirus: An update

HPV16 is sufficient to induce squamous cell carcinoma specifically in the tongue base in transgenic mice

Contact Info

Product

Resources

About