Immunological prevention of spontaneous tumors: a new prospect?

Quaglino, Elena; Rovero, Stefania; Musiani, Piero; Amici, Augusto; Nicoletti, Giordano; Nanni, Patrizia; Forni, Guido

doi:10.1016/s0165-2478(01)00323-6

Cited by 16 publications

(15 citation statements)

References 24 publications

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“…Compared to other transgenic mouse models (e.g., SV40 T-antigen, that recapitulates the same progression in a shorter time-frame) mammary glands of the BALB-neuT mice progress along the different histological stages with a slow rate, showing the first palpable mass at 20 weeks of age. 22 Since this slow transformation closely reflects breast cancer development in patients, the angiogenic vasculature proceeds along with tumour progression in a more natural evolution path. Our results showed microvasculature changes in terms of permeability and vascularization when mammary glands progressed from simple hyperplasia to atypical hyperplasia.…”

Section: Discussionmentioning

confidence: 99%

“…Xenograft models are only representative of advanced stages of cancer, whereas transgenic mice recapitulate the stepwise progression and typical features of several human cancers, preserving the interaction between tumours and the surrounding microenvironment . In the current study, we used the BALB‐neuT transgenic murine model that shows a human‐like breast cancer development, including mammary hyperplasia, atypical hyperplasia, CIS and invasive breast cancer . The BALB‐neuT mice overexpress the activated form of the rat ErbB2 (Her/2‐neu) oncogene, whose amplification is observed in 20–30% of human breast cancer.…”

mentioning

confidence: 99%

“…21 In the current study, we used the BALB-neuT transgenic murine model that shows a human-like breast cancer development, including mammary hyperplasia, atypical hyperplasia, CIS and invasive breast cancer. 22 The BALB-neuT mice overexpress the activated form of the rat ErbB2 (Her/2-neu) oncogene, whose amplification is observed in 20-30% of human breast cancer. The aim of the present study was to evaluate whether DCEand DW-MRI modalities could detect functional tumour microenvironment changes along the multistep carcinogenesis process observed in the BALB-neuT model, before palpable mass formation, compared to normal mammary glands of BALB/c mice.…”

mentioning

confidence: 99%

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Functional imaging of the angiogenic switch in a transgenic mouse model of human breast cancer by dynamic contrast enhanced magnetic resonance imaging

Consolino

Longo

Dastrù

et al. 2016

Intl Journal of Cancer

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Tumour progression depends on several sequential events that include the microenvironment remodelling processes and the switch to the angiogenic phenotype, leading to new blood vessels recruitment. Non-invasive imaging techniques allow the monitoring of functional alterations in tumour vascularity and cellularity. The aim of this work was to detect functional changes in vascularisation and cellularity through Dynamic Contrast Enhanced (DCE) and Diffusion Weighted (DW) Magnetic Resonance Imaging (MRI) modalities during breast cancer initiation and progression of a transgenic mouse model (BALB-neuT mice). Histological examination showed that BALB-neuT mammary glands undergo a slow neoplastic progression from simple hyperplasia to invasive carcinoma, still preserving normal parts of mammary glands. DCE-MRI results highlighted marked functional changes in terms of vessel permeability (K trans , volume transfer constant) and vascularisation (v p , vascular volume fraction) in BALB-neuT hyperplastic mammary glands if compared to BALB/c ones. When breast tissue progressed from simple to atypical hyperplasia, a strong increase in DCE-MRI biomarkers was observed in BALB-neuT in comparison to BALB/c mice (K trans 5 5.3 6 0.7E-4 and 3.1 6 0.5E-4; v p 5 7.4 6 0.8E-2 and 4.7 6 0.6E-2 for BALB-neuT and BALB/c, respectively) that remained constant during the successive steps of the neoplastic transformation. Consistent with DCE-MRI observations, microvessel counting revealed a significant increase in tumour vessels. Our study showed that DCE-MRI estimates can accurately detect the angiogenic switch at early step of breast cancer carcinogenesis. These results support the view that this imaging approach is an excellent tool to characterize microvasculature changes, despite only small portions of the mammary glands developed neoplastic lesions in a transgenic mouse model.Breast cancer typically evolves through a multistep progression process, starting from epithelial hyperplasia and progressing to carcinoma in situ (CIS) and finally to metastatic carcinomas.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Functional imaging of the angiogenic switch in a transgenic mouse model of human breast cancer by dynamic contrast enhanced magnetic resonance imaging

Consolino

Longo

Dastrù

et al. 2016

Intl Journal of Cancer

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“…The inappropriateness of this transposition is illustrated by the fact that when mice are first challenged with a tumor and then immunized, the elicitation of an effective therapeutic response is difficult, and only a minority of mice is cured. Even this limited efficacy is achieved only when the vaccine is administered in the first few days after the tumor challenge [34]. The difficulty in curing transplantable tumors may partially be due to the kinetics of tumor growth that may be so fast to overtake the time necessary for the vaccine to induce an immune response.…”

Section: The Responsibility Of Experimental Modelsmentioning

confidence: 99%

“…The protection induced in young mice may be boosted and last for the life span of the mice [34]. Vaccines against oncoantigens are especially effective in inhibiting the progression of early stages of cancer, while their efficacy decreases as the tumor progresses.…”

Section: Into the Wind Of Experimental Evidence: Vaccines For Tumor Pmentioning

confidence: 99%

Vaccines for tumor prevention: a pipe dream?

Forni

2015

J Infect Dev Ctries

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Whether or not a tumor expresses peculiar antigens that differentiate it from normal cells was intensively investigated in the 1950s. A conclusive answer was provided in 1960 when George Klein showed that a tumor can be rejected by the immune response elicited by a vaccine administered to the same mouse in which the tumor was induced. Whether immunogenicity was a feature restricted only to tumors artificially induced by viruses or by high doses of chemical carcinogens was then hotly debated until Terry Boon showed, in the 1980s, that almost any tumor can be recognized by a syngeneic immune system triggered by an appropriate cancer vaccine. However, the therapeutic efficacy of vaccine-induced immunity against an advanced tumor is marginal. The combination of an anti-tumor vaccine with new sophisticated maneuvers to contrast tumor-induced suppression may yield new and effective therapeutic strategies. Also, the exploitation of tumor vaccines to prevent tumors in cohorts of people with a specific risk of cancer may become a fresh strategy with great potential to control tumor onset.

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The relationship between blood IL‐12p40 level and melanoma progression

Fang

Wang

Chun³

et al. 2014

Intl Journal of Cancer

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Cytokines such as IL-12p70 (“IL-12”) and IL-23 can influence tumor progression. We tested the hypothesis that blood levels of IL-12p40, the common subunit of both cytokines, are associated with melanoma progression. Blood from 2,048 white melanoma patients were collected at a single institution between March 1998 and March 2011. Plasma levels of IL-12p40 were determined for 573 patients (discovery), 249 patients (validation 1), and 244 patients (validation 2). Per 10-unit change of IL-12p40 level was used to investigate associations with melanoma patient outcome among all patients or among patients with early or advanced stage. Among stage I/II melanoma patients in the pooled data set, after adjustment for sex, age, stage and blood draw time from diagnosis, elevated IL-12p40 was associated with melanoma recurrence (hazard ratio[HR]=1.04 per 10-unit increase in IL-12p40, 95% CI 1.02–1.06, P=8.48×10−5); Elevated IL-12p40 was also associated with a poorer melanoma specific survival (HR=1.06, 95% CI 1.03–1.09, P=3.35×10−5) and overall survival (HR=1.05, 95% CI 1.03–1.08, P=8.78×10−7) in multivariate analysis. Among stage III/IV melanoma patients in the pooled data set, no significant association was detected between elevated IL-12p40 and overall survival, or with melanoma specific survival, with or without adjustment for the above covariates. Early-stage melanoma patients with elevated IL-12p40 levels are more likely to develop disease recurrence and have a poorer survival. Further investigation with a larger sample size will be needed to determine the role of IL-12p40 in advanced stage melanoma patients.

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Immunological prevention of spontaneous tumors: a new prospect?

Cited by 16 publications

References 24 publications

Functional imaging of the angiogenic switch in a transgenic mouse model of human breast cancer by dynamic contrast enhanced magnetic resonance imaging

Functional imaging of the angiogenic switch in a transgenic mouse model of human breast cancer by dynamic contrast enhanced magnetic resonance imaging

Vaccines for tumor prevention: a pipe dream?

The relationship between blood IL‐12p40 level and melanoma progression

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