2002 |
Ghanbari, Hossein A |
R43Activity Code Description: To support projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). |
Development of Immunodiagnostics For Pancreatic Cancer @ Panacea Pharmaceuticals, Inc.
DESCRIPTION (provided by applicant): Current methods for the diagnosis and management of neoplastic disease rely heavily on imaging techniques, such as X-ray, CT scanning and MRI, tissue biopsy and histopathological findings. Much effort has been put forth to identify other less costly and less invasive means for the diagnosis and monitoring of cancers. In certain cases specific molecular tumor markers have been identified that show promise as potential diagnostic and prognostic indicators, but unfortunately, most of these markers lack the requisite specificity and sensitivity. The long-term objective of this research program is to develop immunodiagnostic assays for the detection of the tumor marker, human aspartyl (asparaginyl) beta-hydroxylase (HAAH). Recent work has demonstrated the over-expression of HAAH in a wide variety of malignant tumors, including pancreatic carcinoma, glioblastoma multiforme, hepatocellular carcinoma, and cholangiocarcinoma. Additionally, unlike other potential tumor markers, over-expression of HAAH displays high specificity for malignant cells. The dismal prognosis associated with cancer of the pancreas is because very few of these cancers are found prior to their spread to other organs. To date, no molecular markers for pancreatic cancer have been identified, validated and accepted for clinical use for early diagnosis. The Specific Aims of this proposal are to establish HAAH as a soluble marker for pancreatic cancer, to develop highly sensitive and specific immunoassays for the detection of HAAH in bodily fluids, and to correlate the levels of HAAH in the serum and/or pancreatic juice of individuals diagnosed with pancreatic carcinoma to disease diagnosis and patient outcome.
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1 |
2002 |
Ghanbari, Hossein A |
R43Activity Code Description: To support projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). |
Development of Novel Cancer Immunotherapeutics @ Panacea Pharmaceuticals, Inc.
Increased expression of human aspartyl (asparaginyl) beta-hydroxylase (HAAH) has been observed in multiple tumor types. HAAH in tumor cells is localized to the cell surface. Its over-expression is sufficient to induce cellular transformation, increase motility and invasiveness, and establish tumor formation. As such, HAAH represents an important novel target for cancer therapy. Ideal drugs retain high affinity and strong specificity for their target, characteristics that are often associated with antibodies. Unfortunately, in most cases effective antibody therapeutics have yet to be developed due to inherent problems in antibody selection and relatively low overall affinities. Recent advances in antibody engineering have lead to the "directed evolution" of extremely high affinity single-chain antibody fragments (scFv). The primary goal of this work is the development of high affinity scFv that can inhibit or attenuate the tumor cell phenotype. In this Phase I proposal we will investigate the use of anti-HAAH mAbs for the inhibition of the tumor phenotype, evolve high affinity anti-HAAH scFv and test their ability to inhibit tumor cell function. A future Phase II application will explore the use of these high affinity anti-HAAH scFv for the treatment of malignancies in preclinical animal models and ultimately in human clinical trials.
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1 |
2004 |
Ghanbari, Hossein A |
R43Activity Code Description: To support projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). |
Novel Agents For Alzheimer's Disease Therapy @ Panacea Pharmaceuticals, Inc.
DESCRIPTION (provided by applicant): Alzheimer disease (AD) is the most common form of dementia and primarily affects older individuals. Currently approximately 4 million people in the United States (US) are affected with AD, and that number is expected to grow as the US population ages. Almost half of the population over age 85 have Alzheimer's disease. Recent evidence has implicated oxidative stress as playing a primary role in the etiology of AD and has suggested that AD neurons are more prone to the resultant damage. Severe oxidative damage may result in cellular loss of function and ultimately cell death. Anti-oxidative stress therapy may prevent or slow the progression of AD. The clinical studies using vitamin E in AD therapy only show limited and moderate effects due to its poor penetration into the brain and that it can be metabolized to "pro-oxidants" in the body. New and more effective anti-oxidative stress compounds are in great need for AD therapy. We have identified a class of compounds, including a lead candidate PAN-811 (MW195Da), which is neuroavailable and has exhibited potent anti-oxidative stress activity at low micro molar levels. In our in vitro models, comparison studies with vitamin E and lipoic acid, PAN-811 provided much better neuroprotection and a more favorable therapeutic index. In addition, we have established a novel cellular model for evaluating oxidative stress in AD employing olfactory neuroblasts (ONs) from AD patients and age-matched normal controls. Here, we propose to elucidate the mechanism of neuroprotection of PAN-811 and utilize the ON model to further evaluate, characterize and optimize the lead compound for future clinical drug development for AD.
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