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Search: authors:"Susan G Hilsenbeck"

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Unique Breast Cancer Features Within the Vietnamese Population

Medicine Susan G. Hilsenbeck Baylor College of Medicine Background: Breast cancer is known to be a heterogeneous disease across women, and even within individual tumors. However, relatively little is known

Krt6a-Positive Mammary Epithelial Progenitors Are Not at Increased Vulnerability to Tumorigenesis Initiated by ErbB2

While most breast cancers are thought to arise from the luminal layer of the breast tissue, it remains unclear which specific cells in the luminal layer are the cells of origin of breast cancer. We have previously reported that WAP-positive luminal epithelial cells are at increased susceptibility to tumor initiation by ErbB2 compared to the bulk population, while the mammary...

Analysis of phosphatases in ER-negative breast cancers identifies DUSP4 as a critical regulator of growth and invasion

Estrogen receptor (ER)-negative cancers have a poor prognosis, and few targeted therapies are available for their treatment. Our previous analyses have identified potential kinase targets critical for the growth of ER-negative, progesterone receptor (PR)-negative and HER2-negative, or “triple-negative” breast cancer (TNBC). Because phosphatases regulate the function of kinase...

Meta-analysis of multiple microarray datasets reveals a common gene signature of metastasis in solid tumors

Background Metastasis is the number one cause of cancer deaths. Expression microarrays have been widely used to study metastasis in various types of cancer. We hypothesize that a meta-analysis of publicly available gene expression datasets in various tumor types can identify a signature of metastasis that is common to multiple tumor types. This common signature of metastasis may...

Obtaining informed consent for clinical tumor and germline exome sequencing of newly diagnosed childhood cancer patients

Background Effectively educating families about the risks and benefits of genomic tests such as whole exome sequencing (WES) offers numerous challenges, including the complexity of test results and potential loss of privacy. Research on best practices for obtaining informed consent (IC) in a variety of clinical settings is needed. The BASIC3 study of clinical tumor and germline...

Methylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancer is associated with clinical characteristics, but only RASSF1A methylation is associated with outcome

Background Aberrant promoter CpG island hypermethylation is associated with transcriptional silencing. Tumor suppressor genes are the key targets of hypermethylation in breast cancer and therefore may lead to malignancy by deregulation of cell growth and division. Our previous pilot study with pairs of malignant and normal breast tissues identified correlated methylation of two...

The role of single nucleotide polymorphisms in breast cancer metastasis

Our understanding of many aspects of cancer biology has been advanced through the use of modern genetics. These studies have already shown that germ line polymorphisms play a significant role in disease initiation and response to therapy. However, what is less well studied is the role of germ line polymorphisms in cancer progression. Studies in rodents indicate that differential...

A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

Background Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have...

An epigenomic approach to therapy for tamoxifen-resistant breast cancer

journals • PubMed • Google ScholarSearch for Susan G Hilsenbeck in:Nature Research journals • PubMed • Google ScholarSearch for Rainer Lanz in:Nature Research journals • PubMed • Google ScholarSearch for Bin ... , Lei Wang, Xiaoyong Fu, Agostina Nardone, C Kent Osborne, Rachel Schiff & Bert W O'MalleyLester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USAMartin J Shea, Susan G

Selective Small Molecule Stat3 Inhibitor Reduces Breast Cancer Tumor-Initiating Cells and Improves Recurrence Free Survival in a Human-Xenograft Model

Metastasis and disease relapse are hypothesized to result from tumor initiating cells (TICs). Previously, we have defined a CD44+/CD24−/low mammosphere-forming tumorigenic 493-gene signature in breast cancer. Stat3 was identified as a critical node in self-renewal based on an ongoing lentiviral shRNA screen being conducted in two breast cancer cell lines SUM159 and BT549. In...

Circulating and disseminated tumor cells from breast cancer patient-derived xenograft-bearing mice as a novel model to study metastasis

, Fengju Chen, Bianca M. Veneziani, Xiang H. Zhang, Rinath M. Jeselsohn, Susan G. Hilsenbeck, Alejandro Contreras, Carolina Gutierrez, Mothaffar F. Rimawi, C. Kent Osborne, Rachel Schiff, and Meghana V

β1 integrin mediates an alternative survival pathway in breast cancer cells resistant to lapatinib

Introduction The overexpression of human epidermal growth factor receptor (HER)-2 in 20% of human breast cancers and its association with aggressive growth has led to widespread use of HER2-targeted therapies, such as trastuzumab (T) and lapatinib (L). Despite the success of these drugs, their efficacy is limited in patients whose tumors demonstrate de novo or acquired resistance...

Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy

While a first pregnancy before age 22 lowers breast cancer risk, a pregnancy after age 35 significantly increases life-long breast cancer risk. Pregnancy causes several changes to the normal breast that raise barriers to transformation, but how pregnancy can also increase cancer risk remains unclear. We show in mice that pregnancy has different effects on the few early lesions...

The promise of microarrays in the management and treatment of breast cancer

Breast cancer is the most common malignancy afflicting women from Western cultures. Developments in breast cancer molecular and cellular biology research have brought us closer to understanding the genetic basis of this disease. Recent advances in microarray technology hold the promise of further increasing our understanding of the complexity and heterogeneity of this disease...

Loss of Rho GDIα and Resistance to Tamoxifen via Effects on Estrogen Receptor α

Background Estrogen receptor (ER) α is a successful therapeutic target in breast cancer, but patients eventually develop resistance to antiestrogens such as tamoxifen.

Haploinsufficiency for p190B RhoGAP inhibits MMTV-Neu tumor progression

Introduction Rho signaling regulates key cellular processes including proliferation, survival, and migration, and it has been implicated in the development of many types of cancer including breast cancer. P190B Rho GTPase activating protein (RhoGAP) functions as a major inhibitor of the Rho GTPases. P190B is required for mammary gland morphogenesis, and overexpression of p190B in...

Different mechanisms for resistance to trastuzumab versus lapatinib in HER2- positive breast cancers -- role of estrogen receptor and HER2 reactivation

Introduction The human epidermal growth factor receptor 2 (HER2)-targeted therapies trastuzumab (T) and lapatinib (L) show high efficacy in patients with HER2-positive breast cancer, but resistance is prevalent. Here we investigate resistance mechanisms to each drug alone, or to their combination using a large panel of HER2-positive cell lines made resistant to these drugs...

Prevention of Hypovolemic Circulatory Collapse by IL-6 Activated Stat3

Half of trauma deaths are attributable to hypovolemic circulatory collapse (HCC). We established a model of HCC in rats involving minor trauma plus severe hemorrhagic shock (HS). HCC in this model was accompanied by a 50% reduction in peak acceleration of aortic blood flow and cardiomyocyte apoptosis. HCC and apoptosis increased with increasing duration of hypotension. Apoptosis...

Hormones, receptors, and growth in hyperplastic enlarged lobular units: early potential precursors of breast cancer

Introduction The hyperplastic enlarged lobular unit (HELU) is a common alteration in adult female human breast and is the earliest histologically identifiable lesion with premalignant potential. Growth and differentiation in normal epithelium are regulated by estrogen and progesterone, whose effects are mediated through estrogen receptor (ER)-α and progesterone receptor (PR). We...

P190B RhoGAP has pro-tumorigenic functions during MMTV-Neu mammary tumorigenesis and metastasis

Introduction Rho GTPases are overexpressed and hyperactivated in human breast cancers. Deficiency of p190B RhoGAP, a major inhibitor of the Rho GTPases, inhibits mouse mammary tumor virus long terminal repeat (MMTV)-Neu/ErbB2 mammary tumor formation and progression in part through effects within the stromal environment, suggesting that p190B function is pro-tumorigenic. To...