The relationship between obesity and cancer

Obesity is an urgent and growing global health problem. Among other co-morbidities, obesity is associated with a significantly increased risk of developing many cancers. The epidemiological evidence linking obesity and cancer has ignited multiple studies trying to understand how obesity contributes to cancer risk. Although mechanisms underlying the obesity-cancer link are becoming increasingly clearer, they are very complex and still under intense investigation. Strategies that prevent and/or reverse obesity may also be useful for reducing the progression of cancer. Recent interests are focused towards brown fat as a primary target to combat obesity. In this review, we integrate the classic understandings of the mechanistic role of obesity in cancer to the studies which suggest a beneficial role of brown fat to humans

Comparison of Radioimmuno and Carbon Nanotube Field-Effect Transistor Assays for Measuring Insulin-Like Growth Factor-1 in a Preclinical Model of Human Breast Cancer

<p>Abstract</p> <p>Background</p> <p>To realize the promise of personalized medicine, diagnostic instruments used for detecting and measuring biomarkers must become smaller, faster and less expensive. Although most techniques used currently to detect biomarkers are sensitive and specific, many suffer from several disadvantages including their complexity, high cost and long turnaround time. One strategy to overcome these problems is to exploit carbon nanotube (CNT) based biosensors, which are sensitive, use inexpensive disposable components and can be easily adapted to current assay protocols. In this study we investigated the applicability of using a CNT field-effect transistor (CNT-FET) as a diagnostic instrument for measuring cancer biomarkers in serum using a mouse model of <it>Breast Cancer Susceptibility 1</it>-related breast cancer. Insulin like growth factor-1 (IGF-1) was chosen because it is highly relevant in breast cancer and because measuring serum IGF-1 levels by conventional methods is complicated due to specific IGF-1 serum binding proteins.</p> <p>Findings</p> <p>Our results show that there is good correlation between the two platforms with respect to detecting serum IGF-1. In fact, the CNT-FETs required only one antibody, gave real-time results and required approximately 100-fold less mouse serum than the radioimmunoassay.</p> <p>Conclusions</p> <p>Both IGF-1 radioimmuno and CNT-FET assays gave comparable results. Indeed, the CNT-FET assay was simpler and faster than the radioimmunoassay. Additionally, the low serum sample required by CNT-FETs can be especially advantageous for studies constricted by limited amount of human clinical samples and for mouse studies, since animals often need to be sacrificed to obtain enough serum for biomarker evaluation.</p

Department of Pathology, Thomas Jefferson University, Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors.

BACKGROUND: Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors. RESULTS: Unsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int3, TgWAP-Tag, and TgC3(1)-Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models (TgWAP-T121, TgMMTV-Wnt1, Brca1Co/Co;TgMMTV-Cre;p53+/- and DMBA-induced), tumors with a variety of histologies and expression profiles developed. In many models, similarities to human breast tumors were recognized, including proliferation and human breast tumor subtype signatures. Significantly, tumors of several models displayed characteristics of human basal-like breast tumors, including two models with induced Brca1 deficiencies. Tumors of other murine models shared features and trended towards significance of gene enrichment with human luminal tumors; however, these murine tumors lacked expression of estrogen receptor (ER) and ER-regulated genes. TgMMTV-Neu tumors did not have a significant gene overlap with the human HER2+/ER- subtype and were more similar to human luminal tumors. CONCLUSION: Many of the defining characteristics of human subtypes were conserved among the mouse models. Although no single mouse model recapitulated all the expression features of a given human subtype, these shared expression features provide a common framework for an improved integration of murine mammary tumor models with human breast tumors

Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors

Comparison of mammary tumor gene-expression profiles from thirteen murine models using microarrays and with that of human breast tumors showed that many of the defining characteristics of human subtypes were conserved among mouse models

Comparison of mouse mammary gland imaging techniques and applications: Reflectance confocal microscopy, GFP Imaging, and ultrasound

<p>Abstract</p> <p>Background</p> <p>Genetically engineered mouse models of mammary gland cancer enable the <it>in vivo </it>study of molecular mechanisms and signaling during development and cancer pathophysiology. However, traditional whole mount and histological imaging modalities are only applicable to non-viable tissue.</p> <p>Methods</p> <p>We evaluated three techniques that can be quickly applied to living tissue for imaging normal and cancerous mammary gland: reflectance confocal microscopy, green fluorescent protein imaging, and ultrasound imaging.</p> <p>Results</p> <p>In the current study, reflectance confocal imaging offered the highest resolution and was used to optically section mammary ductal structures in the whole mammary gland. Glands remained viable in mammary gland whole organ culture when 1% acetic acid was used as a contrast agent. Our application of using green fluorescent protein expressing transgenic mice in our study allowed for whole mammary gland ductal structures imaging and enabled straightforward serial imaging of mammary gland ducts in whole organ culture to visualize the growth and differentiation process. Ultrasound imaging showed the lowest resolution. However, ultrasound was able to detect mammary preneoplastic lesions 0.2 mm in size and was used to follow cancer growth with serial imaging in living mice.</p> <p>Conclusion</p> <p>In conclusion, each technique enabled serial imaging of living mammary tissue and visualization of growth and development, quickly and with minimal tissue preparation. The use of the higher resolution reflectance confocal and green fluorescent protein imaging techniques and lower resolution ultrasound were complementary.</p

Mechanisms of immune evasion in breast cancer

Abstract Tumors develop multiple mechanisms of immune evasion as they progress, with some cancer types being inherently better at ‘hiding’ than others. With an increased understanding of tumor immune surveillance, immunotherapy has emerged as a promising treatment strategy for breast cancer, despite historically being thought of as an immunologically silent neoplasm. Some types of cancer, such as melanoma, bladder, and renal cell carcinoma, have demonstrated a durable response to immunotherapeutic intervention, however, breast neoplasms have not shown the same efficacy. The causes of breast cancer’s immune silence derive from mechanisms that diminish immune recognition and others that promote strong immunosuppression. It is the mechanisms of immune evasion in breast cancers that are poorly defined. Thus, further characterization is critical for the development of better therapies. This brief review will seek to provide insight into the possible causes of weak immunogenicity and immune suppression mediated by breast cancers and highlight current immunotherapies being used to restore immune responses to breast cancer

Comparison of mouse mammary gland imaging techniques and applications: Reflectance confocal microscopy, GFP Imaging, and ultrasound-2

E same gland . Mammary tumors appear less bright compared to the mammary ducts and more bright compared to tumor associated blood vessels . Lymph nodes can be highlighted close to brighter mammary ducts . H&E section of a lymph node. Arrows: mammary ducts, ^: mammary tumor, open arrowheads: blood vessels, *: lymph node. Magnifications are as indicated.<p><b>Copyright information:</b></p><p>Taken from "Comparison of mouse mammary gland imaging techniques and applications: Reflectance confocal microscopy, GFP Imaging, and ultrasound"</p><p>http://www.biomedcentral.com/1471-2407/8/21</p><p>BMC Cancer 2008;8():21-21.</p><p>Published online 23 Jan 2008</p><p>PMCID:PMC2266934.</p><p></p

Comparison of mouse mammary gland imaging techniques and applications: Reflectance confocal microscopy, GFP Imaging, and ultrasound-8

Supplemented media immediately . Other glands were put into IPAH culture after RCM imaging which was accomplished by injection with either PBS , 1% acetic acid , 3% acetic acid , or 5% acetic acid . Pre-WOC RCM images display examples of terminal end buds which can be compared to the whole mount (WM) image . Alveolar development in the glands can be compared in post-WOC WM and H&E images. Arrowhead: terminal end bud, arrows: alveolar development, *: lymph node. Magnifications are as indicated.<p><b>Copyright information:</b></p><p>Taken from "Comparison of mouse mammary gland imaging techniques and applications: Reflectance confocal microscopy, GFP Imaging, and ultrasound"</p><p>http://www.biomedcentral.com/1471-2407/8/21</p><p>BMC Cancer 2008;8():21-21.</p><p>Published online 23 Jan 2008</p><p>PMCID:PMC2266934.</p><p></p