Cancer Research Institute

About: Cancer Research Institute is a nonprofit organization based out in New York, New York, United States. It is known for research contribution in the topics: Cancer & Population. The organization has 1061 authors who have published 754 publications receiving 26712 citations.

Non-destructive characterization of adult zebrafish models using Jones matrix optical coherence tomography

Abstract: The zebrafish is a valuable vertebrate animal model in pre-clinical cancer research. A Jones matrix optical coherence tomography (JM-OCT) prototype operating at 1310 nm and an intensity-based spectral-domain OCT setup at 840 nm were utilized to investigate adult wildtype and a tumor-developing zebrafish model. Various anatomical features were characterized based on their inherent scattering and polarization signature. A motorized translation stage in combination with the JM-OCT prototype enabled large field-of-view imaging to investigate adult zebrafish in a non-destructive way. The diseased animals exhibited tumor-related abnormalities in the brain and near the eye region. The scatter intensity, the attenuation coefficients and local polarization parameters such as the birefringence and the degree of polarization uniformity were analyzed to quantify differences in tumor versus control regions. The proof-of-concept study in a limited number of animals revealed a significant decrease in birefringence in tumors found in the brain and near the eye compared to control regions. The presented work showed the potential of OCT and JM-OCT as non-destructive, high-resolution, and real-time imaging modalities for pre-clinical research based on zebrafish.

γ-Glutamylcysteine Synthetase and L-Buthionine-(S,R)-Sulfoximine: A New Selection Strategy for Gene-Transduced Neural and Hematopoietic Stem/Progenitor Cells

Abstract: In most experimental gene therapy protocols involving stem/progenitor cells, only a small fraction of cells, often therapeutically inadequate, can be transduced and made to express the therapeutic gene. A promising strategy for overcoming this problem is the use of a dominant selection marker, such as a drug resistance gene. In this paper, we explore the potential of the heavy subunit of gamma-glutamylcysteine synthetase (gamma-GCSh) to act as a selection marker. We found that 3T3 fibroblasts transduced with the bicistronic retroviral vector SF91/GCSh-eGFP, encoding gamma-GCSh and the enhanced green fluorescent protein (eGFP), were highly resistant to L-buthionine-(S,R)-sulfoximine (BSO), a gamma-GCS inhibitor with a low clinical toxicity profile. The level of resistance was not proportional to the increase in intracellular glutathione. In fact, cells overexpressing both heavy and light gamma-GCS subunits had higher intracellular GSH levels, and a lower level of resistance to the cytotoxic activity of BSO, compared with cells overexpressing gamma-GCSh alone. 3T3 fibroblasts overexpressing gamma-GCSh could be selected from cultures containing both naive and gene-modified cells by application of exogenous BSO selection pressure for 4 days. Also, primary neural stem/progenitor cells derived from the lateral ventricles of mouse neonatal brains and primary hematopoietic stem/progenitor cells (HSCs/HPCs) from mouse bone marrow, transduced with the gamma-GCSh-eGFP vector, could be selected by BSO treatment in vitro. On ex vivo BSO selection and reimplantation into a syngeneic myeloablated host, donor HSCs/HPCs repopulated the marrow and continued to express the transgene(s). These results provide proof of principle that somatic stem/progenitor cells, transduced simultaneously with a potentially curative gene and gamma-GCSh, can be selected by treatment with BSO before in vivo transplantation.

Functional assessment of intrinsic disorder central domains of BRCA1

Abstract: The most studied function of BRCA1 is that of tumor suppression through its role in DNA repair and transcription regulation. Germline mutations discovered in a larger cohort of patients, abrogate BRCA1 interactions with reported cellular partners, and are responsible for breast and ovarian cancer. The different functional regions of BRCA1 interact with nearly 30 different cellular partners. Thus, it becomes clinically significant to understand the detailed protein-protein interactions associated with functional regions of BRCA1. Different overlapping central domains of BRCA1 have been characterized using in silico, in vitro and biophysical approaches. To our conclusions, it has been observed that central domains of BRCA1 are intrinsically disordered and has large hydrodynamic radius with random coil like structures.