Research
Researchers in the lab are focused on identifying lesions associated with the tumorigenesis and metastasis. The Surgical Oncology Tumor Bank has been invaluable in advancing this research possible. For example, the lab was able to help validate the role of microRNAs in a mouse model of pancreatic neuroendocrine tumors using human neuroendocrine tumor specimens. The lab is also investigating the role of Sall2 in conferring resistance to cancer therapies, how TNFR1 signaling contributes to the inflammatory response and cell apoptosis, and the role of colon cancer stem cells in perpetuating tumor growth.
Tumor suppressor proteins are the brakes that impede the deregulated and inappropriate cell growth found in cancer. Under the leadership of Dr. Warren, members of the Surgical Oncology Research Laboratory have been scanning the genome of human metastatic colon cancer samples, and other malignancies as well, in order to identify lesions arising from mutated or inappropriately expressed tumor suppressors. A particularly interesting tumor suppressor is Mig-6, which inhibits signaling events induced by activated receptor protein tyrosine kinases. In a study
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The Surgical Oncology tissue bank is a repository for patient tumor specimens and matched normal tissue accumulated by UCSF surgeon-scientists Robert Warren and Eric Nakakura These specimens can be matched to clinical outcomes and the genes encoding important tumor suppressors and oncogens proteins been sequenced in each specimen, making them an invaluable research tool. We have been able to grow these well-characterized tumor specimens in mice. The tumors retain the properties of the human malignancy, thus permitting us to test
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Drs. Pincheira, Donner, and Warren have identified a novel factor called Sall2 that binds cell surface receptors for nerve growth factor. Sall2 appears to act at the cell surface to coordinate the activities of the nerve growth factor receptors and within the nucleus of the cell to regulate gene expression. The genes affected by Sall2 play an important role in regulating the development of neurons, most particularly in the development and extension of neurites from developing neurons. Thus, collaborative efforts
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By implanting human tumors into mice, UCSF researchers have also isolated what we believe are colon cancer stem cells. These are cells which have properties similar to adult human stem cells, such as the capacity for self-renewal and the ability to differentiate into various types of specialized cells. One hypothesis is that cancer stem cells are resistant to traditional chemotherapy treatment; over time, a recurrent tumor may derive from these cancer stem cells. By working to understand the molecular biology
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Signaling through receptors that contain cytoplasmic death domains can induce cancers to regress or in some instances may paradoxically promote the growth and spread of malignancies. The decision-making that underlies whether cancer cells can be induced to self-destruct in response to cytokines such as tumor necrosis factor has been studied, and yet not well understood, for decades. The Surgical Oncology Research Team has shown that the type 1 TNF receptor (TNFR1), a prototype for understanding how cytokines act in cells
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Neuroendocrine (NE), or carcinoid, tumors of the GI tract frequently metastasize. Surgery is often not possible for patients with advanced disease, and current therapies are ineffective for shrinking tumors and durable palliation of debilitating symptoms. Our lab and others have made significant advances in the understanding of the biology of NE tumors: We have identified the Notch signaling pathway as an important regulator of NE tumor growth and hormone production. As a result, clinical trials of Notch activators are being
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The Surgical Oncology Tumor Bank contains tissue samples from more than 500 individual tumors that the lab has examined and catalogued, as well as a database of related information. By analyzing the growing body of data, we hope to identify a manageable number of subgroups - perhaps 10 or fewer - that will teach us how to predict cancer progression, and which treatments are most effective for each subgroup. We may find that some of these genetic subgroups of tumors
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