Prevention of breast tumour development in vivo by downregulation of the p185neureceptor

1995 ◽  
Vol 1 (7) ◽  
pp. 644-648 ◽  
Author(s):  
Makoto Katsumata ◽  
Tadao Okudaira ◽  
Arabinda Samanta ◽  
Douglas P. Clark ◽  
Jeffrey A. Drebin ◽  
...  
Keyword(s):  
Breast Tumour ◽  
Tumour Development

scholarly journals ISGylation drives basal breast tumour progression by promoting EGFR recycling and Akt signalling

2019 ◽  
Author(s):  
Alfonso Bolado-Carrancio ◽  
Morwenna Muir ◽  
Ailith Ewing ◽  
Kenneth Macleod ◽  
William Gallagher ◽  
...  
Keyword(s):  
Egf Receptor ◽  
Tumour Progression ◽  
Survival Rates ◽  
Breast Tumour ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Akt Activation ◽  
Gdp Dissociation Inhibitor

ABSTRACTISG15 is an ubiquitin-like modifier that is associated with reduced survival rates in breast cancer patients. However, the mechanism by which ISG15 achieves this remains elusive. We demonstrate that modification of Rab GDP-Dissociation Inhibitor Beta (GDI2) by ISG15 (ISGylation) alters endocytic recycling of the EGF receptor (EGFR). By regulating EGFR trafficking, ISGylation sustains Akt-signalling in vitro and in vivo. Persistent and enhanced Akt activation explains the more aggressive tumour behaviour observed in animal models and human breast cancers. We show that ISGylation can act as driver of tumour progression rather than merely being a marker of it.

scholarly journals Optimization of microbubble enhancement of hyperthermia for cancer therapy in an in vivo breast tumour model

PLoS ONE ◽  
2020 ◽  
Vol 15 (8) ◽  
pp. e0237372
Author(s):  
Deepa Sharma ◽  
Holliday Cartar ◽  
Niki Law ◽  
Anoja Giles ◽  
Golnaz Farhat ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Breast Tumour ◽  
Tumour Model

scholarly journals The spectraplakin Dystonin antagonizes YAP activity and suppresses tumourigenesis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Praachi B. Jain ◽  
Patrícia S. Guerreiro ◽  
Sara Canato ◽  
Florence Janody
Keyword(s):  
Breast Cancer ◽  
Breast Tumour ◽  
Tissue Growth ◽  
Tumour Suppressor ◽  
Aberrant Expression ◽  
Breast Epithelial Cells ◽  
Mcf10a Cells ◽  
Resistance To Doxorubicin ◽  
Candidate Tumour Suppressor

AbstractAberrant expression of the Spectraplakin Dystonin (DST) has been observed in various cancers, including those of the breast. However, little is known about its role in carcinogenesis. In this report, we demonstrate that Dystonin is a candidate tumour suppressor in breast cancer and provide an underlying molecular mechanism. We show that in MCF10A cells, Dystonin is necessary to restrain cell growth, anchorage-independent growth, self-renewal properties and resistance to doxorubicin. Strikingly, while Dystonin maintains focal adhesion integrity, promotes cell spreading and cell-substratum adhesion, it prevents Zyxin accumulation, stabilizes LATS and restricts YAP activation. Moreover, treating DST-depleted MCF10A cells with the YAP inhibitor Verteporfin prevents their growth. In vivo, the Drosophila Dystonin Short stop also restricts tissue growth by limiting Yorkie activity. As the two Dystonin isoforms BPAG1eA and BPAG1e are necessary to inhibit the acquisition of transformed features and are both downregulated in breast tumour samples and in MCF10A cells with conditional induction of the Src proto-oncogene, they could function as the predominant Dystonin tumour suppressor variants in breast epithelial cells. Thus, their loss could deem as promising prognostic biomarkers for breast cancer.

scholarly journals The constitutively active PKG II mutant effectively inhibits gastric cancer development via a blockade of EGF/EGFR-associated signalling cascades

2018 ◽  
Vol 10 ◽  
pp. 175883401775163 ◽  
Author(s):  
Yan Wu ◽  
Miaomiao Yuan ◽  
Wenbin Su ◽  
Miaolin Zhu ◽  
Xiaoyuan Yao ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Cyclic Guanosine Monophosphate ◽  
Inhibitory Effect ◽  
Guanosine Monophosphate ◽  
Tumour Development ◽  
Gastric Tumour ◽  
Signalling Cascades ◽  
Constitutively Active

Type II cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG II) is a membrane-anchored enzyme expressed mainly in the intestinal mucosa and the brain, and is associated with various physiological or pathological processes. Upregulation of PKG II is known to induce apoptosis and inhibit proliferation and metastasis of cancer cells. The inhibitory effect of PKG II has been shown to be dependent on the inhibition of the activation of epidermal growth factor receptor (EGFR) and blockade of EGFR downstream signal transduction in vitro. However, it remains unclear whether similar phenomena/mechanisms exist in vivo and whether these effects are independent of cGMP or cGMP analogues. In the present work, nude mice with transplanted orthotopic tumours were infected with adenovirus encoding cDNA of constitutively active PKG II mutant (Ad-a-PKG II) and the effect of constitutively active PKG II (a-PKG II) on tumour development was detected. The results showed that a-PKG II effectively ameliorated gastric tumour development through delaying the growth, inducing the apoptosis, and inhibiting the metastasis and angiogenesis. The effect was related to blockade of EGFR activation and abrogation of the downstream signalling cascades. These findings provide novel insight which will benefit the development of new cancer therapies.

[11C]Choline-PET imaging of breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1110-1110
Author(s):  
L. M. Kenny ◽  
R. C. Coombes ◽  
K. Contractor ◽  
J. Stebbing ◽  
A. Al-Nahhas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Imaging Modality ◽  
Imaging Techniques ◽  
Treatment Strategies ◽  
Breast Tumour ◽  
Response To Treatment ◽  
Choline Uptake ◽  
Choline Pet ◽  
Arterial Plasma

1110 Background: Molecular imaging techniques are increasingly being used in cancer diagnosis, staging, and assessment of response to treatment. This study sought to evaluate, for the first time, [11C]choline-PET in patients with breast cancer. The potential of [11C]choline-PET for differentiating tumours from normal tissue, correlation with molecular markers, determine its normal variability range, and finally the effect of trastuzumab on [11C]choline uptake in patients with breast cancer was investigated. Methods: 21 patients with newly diagnosed and recurrent breast cancer AJCC stage II-IV were enrolled in the study, all of whom had a baseline dynamic [11C]choline-PET scan with arterial sampling. 14 patients had 2 [11C]choline-PET scans to examine reproducibility, and 7 had a scan after trastuzumab. Analysis of [11C]choline uptake was measured using SUV, Ki (irreversible retention), and IRF@60min (retention using spectral analysis). Results: Breast tumour lesions were visualised by [11C]choline PET in all patients. The difference in tumour and non-tumour uptake were significant for SUV, Ki, and IRF@60 min (Wilcoxon p < 0.0001 for all parameters). [11C]choline uptake was reproducible in breast tumour lesions (r2 = 0.945 for SUV, 0.894 for Ki, and 0.799 for IRF60). The metabolism analysis of arterial plasma samples in 19 patients showed that [11C]choline decreased rapidly post-injection such that at 60 mins the mean radioactivity in arterial plasma due to choline was 15.15 ± 2.16%.Early responses to trastuzumab were determined to be significant in 5 lesions which corresponded with 3 clinical responses. Conclusions: [11C]choline-PET is a promising imaging modality in breast cancer, and could play an important role for determining response to novel treatment strategies in vivo. No significant financial relationships to disclose.

scholarly journals HRAS is a therapeutic target in malignant chemo-resistant adenomyoepithelioma of the breast

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ivan Bièche ◽  
Florence Coussy ◽  
Rania El-Botty ◽  
Sophie Vacher ◽  
Sophie Château-Joubert ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Braf Inhibitor ◽  
Metastatic Potential ◽  
Mek Inhibitor ◽  
Breast Tumour ◽  
Axillary Metastasis ◽  
Small Series ◽  
Recurrent Mutations ◽  
Genetic Features

AbstractMalignant adenomyoepithelioma (AME) of the breast is an exceptionally rare form of breast cancer, with a significant metastatic potential. Chemotherapy has been used in the management of advanced AME patients, however the majority of treatments are not effective. Recent studies report recurrent mutations in the HRAS Q61 hotspot in small series of AMEs, but there are no preclinical or clinical data showing H-Ras protein as a potential therapeutic target in malignant AMEs. We performed targeted sequencing of tumours’ samples from new series of 13 AMEs, including 9 benign and 4 malignant forms. Samples from the breast tumour and the matched axillary metastasis of one malignant HRAS mutated AME were engrafted and two patient-derived xenografts (PDX) were established that reproduced the typical AME morphology. The metastasis-derived PDX was treated in vivo by different chemotherapies and a combination of MEK and BRAF inhibitors (trametinib and dabrafenib). All malignant AMEs presented a recurrent mutation in the HRAS G13R or G12S hotspot. Mutation of PIK3CA were found in both benign and malignant AMEs, while AKT1 mutations were restricted to benign AMEs. Treatment of the PDX by the MEK inhibitor trametinib, resulted in a marked anti-tumor activity, in contrast to the BRAF inhibitor and the different chemotherapies that were ineffective. Overall, these findings further expand on the genetic features of AMEs and suggest that patients carrying advanced HRAS-mutated AMEs could potentially be treated with MEK inhibitors.

scholarly journals Targeting lactate transport suppresses in vivo breast tumour growth

Oncotarget ◽  
2015 ◽  
Vol 6 (22) ◽  
pp. 19177-19189 ◽  
Author(s):  
Filipa Morais-Santos ◽  
Sara Granja ◽  
Vera Miranda-Gonçalves ◽  
António H.J. Moreira ◽  
Sandro Queirós ◽  
...  
Keyword(s):  
Tumour Growth ◽  
Breast Tumour ◽  
Lactate Transport

scholarly journals Phased-array combination of 2D MRS for lipid composition quantification in patients with breast cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vasiliki Mallikourti ◽  
Sai Man Cheung ◽  
Tanja Gagliardi ◽  
Nicholas Senn ◽  
Yazan Masannat ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lipid Composition ◽  
Optimal Algorithm ◽  
Signal To Noise Ratio ◽  
Breast Tumour ◽  
Correlation Spectroscopy ◽  
Acquisition Time ◽  
Double Quantum ◽  
Internal Reference

AbstractLipid composition in breast cancer, a central marker of disease progression, can be non-invasively quantified using 2D MRS method of double quantum filtered correlation spectroscopy (DQF-COSY). The low signal to noise ratio (SNR), arising from signal retention of only 25% and depleted lipids within tumour, demands improvement approaches beyond signal averaging for clinically viable applications. We therefore adapted and examined combination algorithms, designed for 1D MRS, for 2D MRS with both internal and external references. Lipid composition spectra were acquired from 17 breast tumour specimens, 15 healthy female volunteers and 25 patients with breast cancer on a clinical 3 T MRI scanner. Whitened singular value decomposition (WSVD) with internal reference yielded maximal SNR with an improvement of 53.3% (40.3–106.9%) in specimens, 84.4 ± 40.6% in volunteers, 96.9 ± 54.2% in peritumoural adipose tissue and 52.4% (25.1–108.0%) in tumours in vivo. Non-uniformity, as variance of improvement across peaks, was low at 21.1% (13.7–28.1%) in specimens, 5.5% (4.2–7.2%) in volunteers, 6.1% (5.0–9.0%) in peritumoural tissue, and 20.7% (17.4–31.7%) in tumours in vivo. The bias (slope) in improvement ranged from − 1.08 to 0.21%/ppm along the diagonal directions. WSVD is therefore the optimal algorithm for lipid composition spectra with highest SNR uniformly across peaks, reducing acquisition time by up to 70% in patients, enabling clinical applications.

scholarly journals Effects of glucose feeding on tumour development in vivo

1968 ◽  
Vol 22 (1) ◽  
pp. 110-115 ◽  
Author(s):  
Leena Mallick ◽  
S K Banerjee ◽  
G C Shrivastava
Keyword(s):  
Tumour Development ◽  
Glucose Feeding
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