Tissues samples collected during medical procedures, such as biopsies, are used to diagnose a wide variety of diseases. Before diagnosis, patient samples are typically processed by fixation and paraffin embedding. This fixation/embedding process is used to preserve tissue morphology and histology for subsequent evaluation. Unfortunately, most fixative agents can damage or destroy nucleic acids (RNA and DNA) and damage proteins during the fixation process, thereby potentially impairing diagnostic assessment of tissue.

The thymus is an integral part of the adaptive immune system as it generates T cells. Its function diminishes rapidly as the body ages, leading to a compromise of the immune system in the elderly. Reconstitution of adaptive immunity through mass production of different T cell types is therefore a therapeutic need in immunocompromised populations. Furthermore, production of T cells with specific receptors targeting cancer cells is an important cancer immunotherapy approach.

In collaboration with surgery specialists from Johns Hopkins University, researchers at the National Cancer Institute (NCI) developed novel hydrogel compositions and methods of using them in the microsurgical suturing of blood vessels, which is particularly beneficial for surgeons in whole tissue transplant procedures. The lead candidate electropositive hydrogels, called APC1, was demonstrated in anastomosis mice models to be well tolerated, biocompatible, and non-toxic.

Tuberculosis (TB) is an infectious disease that typically affects the lungs. Current therapies include a panel of antibiotics given over a range of 6-9 months. As a result of the expense of treatment, the extended timeframe needed for effective treatment, and the scarcity of medicines in some developing countries, patient compliance with TB treatment is very low and results in multi-drug resistant TB (MDR-TB). There remains a need for a faster, more effective treatment for TB.

The occurrence of thyroid cancer has been increasing in the United States. For some patients, with particularly advanced and metastatic cancer, current treatments such as thyroidectomy and adjuvant radioactive iodine therapy can lead to poor outcomes. Hence, there is a need for new thyroid cancer treatments.

BRAF is an oncogene that encodinges a serine-threonine kinase (B-Raf kinase) important in regulating cell growth and differentiation. Spontaneous mutations in the BRAF gene allow cells to continuously divide, leading to the development of cancer. A substitution of glutamic acid for valine at amino acid number 600 (designated V600E) accounts for 90% of BRAF mutations and is a driver of many cancers. The V600E mutation is present in ~3% of all cancer cases, representing a patient population of 540,000 patients per year.

Scientists at the NCI developed a research tool, a murine cell line model (JygMC(A)) with a reporter construct, of spontaneous metastatic mammary carcinoma that resembles the human breast cancer metastatic process in a triple negative mammary tumor. The assay is useful for screening compounds that specifically inhibit pathways involved in mammary carcinoma and can improve clinical management of of triple negative breast cancer that are greatly refractory to conventional chemo and radiotherapy.

This technology from the NCI Molecular Imaging Program relates to a Zirconium-89 (89Zr)-oxine complex for cell labeling, tracking of labeled cells by whole-body positron emission tomography/computed tomography (PET/CT) imaging, and associated methods. A long half-life of 89Zr (78.4 hours), high sensitivity of PET, and absence of background signal in the recipient enable tracking cells over a week using low levels of labeling radioactivity without causing cellular toxicity.

Englerin A, a natural product, has shown growth-inhibiting activity against renal cancer cell lines. The compound is an agonist of protein kinase C (PCK) theta, which results in cell cytotoxicity, insulin inhibition, and selective activation of viral replication in T cells.  Englerin A derivatives are promising treatment strategies for any diseases associated with PKC theta and/or ion channel proteins.

The Office of the Director, National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research (using the Cooperative Research and Development Agreement (CRADA) or Material Transfer Agreement (MTA) to further develop, evaluate, or commercialize the software for accurate segmentation of cell nuclei and FISH signals in tissue sections.  Collaborators working in the field of quantitative and automated pathology may be interested.