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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.

Researchers at the NCI Center for Molecular Microscopy invented a device to hold transmission electron microscopy grids that allows adherent mammalian cells to be grown on it, as well as the 3D printing software to create the holder.  The TEM cell grid holder solves the difficulty of lifting the TEM grid out of a plate without bending or damaging the grid.  The holder can be reproduced in various sizes with 3D printing. 

Researchers at the National Cancer Institute’s Biopharmaceutical Development Program recently developed massively parallel sequencing methods for virus-derived therapeutics such as viral vaccines and oncolytic immunotherapies.

This technology provides improved processes for production and purification of nucleic acid-containing compositions, such as non-naturally occurring viruses, for example, recombinant polioviruses that can be employed as oncolytic agents. Some of the improved processes relate to improved processes for producing viral DNA template.

The AKT pathway plays a key role in the regulation of cellular survival, apoptosis, and protein translation and has been shown to have prognostic significance in a number of cancers.  Recently, the inventors have identified several functions of the AKT pathway in certain cancers, such as extrahepatic cholangiocarcinoma (EHCC).

B-cell chronic lymphocytic leukemia (B-CLL) is a cancer characterized by a progressive accumulation of functionally incompetent lymphocytes.  Despite high morbidity and mortality, the only available potential cure is allogeneic hematopoietic stem cell transplantation (alloHSCST).  However, there is less than a 50% chance of finding a matching bone marrow or blood donor for B-CLL patients.  Other clinically tested targeted therapies such as rituximab and alemtuzumab target both malignant and normal B cells, resulting in immunosuppression.

Molecular profiling with high throughput assays has gained utility in the management of select cancer patients and several gene expression-based assays are now marketed for improved prognostic accuracy for patients with cancer.

The development of an effective HIV vaccine has been an ongoing area of research. The high variability in HIV-1 virus strains has represented a major challenge in successful development.  Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV.  Two major hurdles to overcome are immunodominance and sequence diversity.  This vaccine utilizes a strategy for overcoming these two issues by identifying the conserved regions of the virus and exploiting them for use in a targeted therapy. 

Neuroblastoma is a rare pediatric cancer that affects one in every hundred thousand children under the age of fifteen in the United States. Current standards of care  are chemotherapy and surgery, followed by stem-cell treatments, radiation and anti-ganglioside antibody therapy, which yield an average three-year survival rate of 10-45%. This demonstrates a need for more effective therapies.

Alterations in microRNAs (miRNAs), a type of small non-coding RNAs, have been reported in cells/tumors subjected to radiation exposure, implying that miRNAs play an important role in cellular stress response to radiation. NCI researchers evaluated small non-coding RNAs, long non-coding RNAs (lncRNA), and mRNA, as potential non-invasive biomarkers for radiation biodosimetry. While the use of miRNAs as radiation biomarkers has been reported, the integrated use of miRNAs, mRNAs and lncRNAs to accurately determine radiation doses is novel and has not been published.