Breast Cancer A Leading Cause Of Death
Abstract Metastasis is the leading cause of cancer death. Of all the processes involved in tumorigenesis, local invasion and the formation of metastases are the most clinically relevant, but the least understood.
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Intratumoral hypoxia, found in the majority of solid tumors, is associated with an increased risk of metastasis and treatment failure. Cancer cells adapt to the hypoxic microenvironment by increasing the activity of the hypoxia-inducible factors HIF-1 and HIF The mechanisms that drive HIF- regulated metastasis must be determined in order to identify effective treatment strategies with the potential to block metastasis. We also showed that collagen hydroxylase enzymes were essential for the spontaneous metastasis of breast cancer cells to the lung and lymph nodes of mice. On the other hand, we found that hypoxia induced the expression of integrin receptors in an ECM-independent manner. These observations led us to propose a model in which HIFs simultaneously induce the production of ECM components ligands and their integrin receptors to potentiate downstream signaling events which synergistically enhance metastasis.
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The proposed research will test this model by generating physiological ECM substrates which recapitulate the composition of ECM in vivo. In aim 1, we will test the hypothesis that HIF-1 or HIF-2 transcriptionally regulates the expression of several integrin subunits in cancer cells. During the mentored K99 phase, we will identify the HIF-dependent pattern of integrin gene expression under hypoxia. During the independent R00 phase, the mechanism of HIF-regulation of integrins will be determined.
In aim 2, we will test the hypothesis that hypoxia-induced and HIF-dependent integrin expression causes an increase in ECM adhesion, motility, invasion and matrix contraction in a 3D culture model system using novel biophysical assays. During the mentored K99 phase, cell lines will be generated to counteract the effect of hypoxia on integrin expression and tested in the assays described. In aim 3, we will test the hypothesis that culturing breast cancer cells on ECM produced under hypoxic conditions will potentiate downstream integrin signaling.
In the K99 phase, we will determine whether integrin expression is potentiated by interactions with a hypoxic ECM. In the R00 phase, we will test the hypothesis that some of the integrins induced under hypoxic conditions are required for HIF-induced metastasis. With this information in hand, during the R00 phase, we will systematically evaluate each step in the metastatic cascade using animal models to determine which steps require integrin s expression by breast cancer cells aim 4. Taken together, we hope this data will lead link novel strategies for the treatment of metastatic breast cancer.
The unique environment at Johns Hopkins has many advantages that will serve to support my training and research plans as well as my future scientific career. My primary mentor, Dr. Semenza and co-mentor, Dr. Denis Wirtz, are leaders in their respective fields.
Their leadership together with an intensive career development training plan and the K99 award will facilitate my transition to a successful independent scientist. Public Health Relevance Metastasis is the leading cause of cancer death.
The mechanisms that drive hypoxia-related metastasis must be determined in order to identify effective treatment strategies for cancer patients. To this end, we will investigate the role of th hypoxic extracellular matrix on integrin induction and breast cancer metastasis.]
Breast Cancer A Leading Cause Of Death - sorry, that
Breast cancer is the most common cancer in American women, except for skin cancers. This means there is a 1 in 8 chance she will develop breast cancer. This also means there is a 7 in 8 chance she will never have the disease. Current year estimates for breast cancer The American Cancer Society's estimates for breast cancer in the United States for are: About , new cases of invasive breast cancer will be diagnosed in women. About 49, new cases of ductal carcinoma in situ DCIS will be diagnosed. About 43, women will die from breast cancer. Trends in breast cancer incidence In recent years, incidence rates have increased by 0. Trends in breast cancer deaths Breast cancer is the second leading cause of cancer death in women.Like your: Breast Cancer A Leading Cause Of Death
| THE METAMORPHOSIS ESSAY QUESTIONS | 2 days ago · Breast Cancer- Leading Cause of Death Words | 6 Pages ovulatory cycles, all of which lower estrogen levels. Breast cancers occurs when genetic mutations, or somatic mutations, that metastasized in critical genes allow buildups of cells to grow undisciplined and embody a tumor. 18 hours ago · Breast cancer is the most common kind of cancer among American women, except for skin cancer, and the second leading cause of cancer death in women, exceeded only by lung cancer. But emerging knowledge offers reason for optimism. Here are five things women should know about breast cancer, according to Esserman. 1. Breast cancer isn’t one disease. 2 days ago · Cardiovascular disease is a leading cause of death in breast cancer survivors, but the underlying cause is not fully characterised. Aims To determine whether insulin sensitivity, cardiovascular risk markers and body composition were perturbed in women treated with chemotherapy for early stage breast cancer and whether perturbations occurred. |
| Breast Cancer A Leading Cause Of Death | 2 days ago · Breast Cancer- Leading Cause of Death Words | 6 Pages ovulatory cycles, all of which lower estrogen levels. Breast cancers occurs when genetic mutations, or somatic mutations, that metastasized in critical genes allow buildups of cells to grow undisciplined and embody a tumor. 15 hours ago · Breast cancer is the most common cause of cancer among women, and it is a worldwide health problem not only because of its severe clinical manifestations and high mortality but also because of the great variety of genetics and environmental risk factors related. 1 day ago · Though, the clinical management of breast cancer has improved significantly over the past 30 years, it still remains the leading cause of cancer-related female death worldwide. Prevention is the fundamental issue in breast cancer control, for which identification markers in terms of initiation and promotion are necessary. To understand this, an animal model which can. |
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