INEL BNCT Research Program, May/June 1992

This report presents summaries for two months of current research of the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Program. Information is presented on development and murine screening experiments of low-density lipoprotein, carboranyl alanine, and liposome boron containing compounds. Pituitary tumor cell culture studies are described. Drug stability, pharmacology and toxicity evaluation of borocaptate sodium (BSH) and boronophenylaianine (IBPA) are described. Treatment protocol development via the large animal (canine) model studies and physiological response evaluation in rats are discussed. Supporting technology development and technical support activities for boron drug biochemistry and purity, analytical and measurement dosimetry, and noninvasive boron quantification activities are included for the current time period. Current publications for the two months are listed

Experimental Transport Benchmarks for Physical Dosimetry to Support Development of Fast-Neutron Therapy with Neutron Capture Augmentation

The Idaho National Laboratory (INL), the University of Washington (UW) Neutron Therapy Center, the University of Essen (Germany) Neutron Therapy Clinic, and the Northern Illinois University(NIU) Institute for Neutron Therapy at Fermilab have been collaborating in the development of fast-neutron therapy (FNT) with concurrent neutron capture (NCT) augmentation [1,2]. As part of this effort, we have conducted measurements to produce suitable benchmark data as an aid in validation of advanced three-dimensional treatment planning methodologies required for successful administration of FNT/NCT. Free-beam spectral measurements as well as phantom measurements with Lucite{trademark} cylinders using thermal, resonance, and threshold activation foil techniques have now been completed at all three clinical accelerator facilities. The same protocol was used for all measurements to facilitate intercomparison of data. The results will be useful for further detailed characterization of the neutron beams of interest as well as for validation of various charged particle and neutron transport codes and methodologies for FNT/NCT computational dosimetry, such as MCNP [3], LAHET [4], and MINERVA [5]

INEL BNCT research program, July--August 1992

This report presents summaries for two months of current research of the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Program. Information is presented on development and murine screening experiments of low-density lipoprotein, carboranyl alanine, and liposome boron containing compounds. Pituitary tumor cell culture studies are described. Drug stability, pharmacology and toxicity evaluation of borocaptate sodium (BSH) and boronophenylalanine (BPA) are described. Treatment protocol development via the large animal (canine) model studies and physiological response evaluation in rats are discussed. Supporting technology development and technical support activities for boron drug biochemistry and purity, analytical and measurement dosimetry, and noninvasive boron quantification activities are included for the current time period. Current publications for the two months are listed

Validation of computational methods for treatment planning of fast-neutron therapy using activation foil techniques

A closed-form direct method for unfolding neutron spectra from foil activation data is presented. The method is applied to measurements of the free-field neutron spectrum produced by the proton-cyclotron-based fast-neutron radiotherapy facility at the University of Washington (UW) School of Medicine. The results compare favorably with theoretical expectations based on an a-priori calculational model of the target and neutron beamline configuration of the UW facility

Flooded by jargon: How the interpretation of water-related terms differs between hydrology experts and the general audience

Communication about water-induced hazards (such as floods, droughts or levee breaches) is important, in order to keep their impact as low as possible. However, sometimes the boundary between specialized and non-specialized language can be vague. Therefore, a close scrutiny of the use of hydrological vocabulary by both experts and laypeople is necessary. In this study, we compare the expert and layperson definitions of 22 common terms and pictures related to water and water hazards, to see where misunderstandings might arise both in text and pictures. Our primary objective is to analyze the degree of agreement between experts and laypeople in their definition of the used terms. In this way, we hope to contribute to improving the communication between these groups in the future. Our study was based on a survey completed by 34 experts and 119 laypeople. Especially concerning the definition of words related to water there are some profound differences between experts and laypeople: words like "river" and "river basin" turn out to have a thoroughly different interpretation between the two groups. Concerning the pictures, there is much more agreement between the groups.Water Resource

Targeting glucose and glutamine metabolism combined with radiation therapy in non-small cell lung cancer

Item does not contain fulltextPURPOSE: Metabolic inhibition might sensitize tumors to irradiation. Here, we examined the effect of lonidamine (several metabolic effects, inhibiting hexokinase amongst others) and/or 968 (glutaminase inhibitor) on tumor cell metabolism, cell growth, cytotoxicity and radiosensitivity in NSCLC cell lines in vitro in relation to histology. MATERIALS AND METHODS: Adeno- (H23, HCC827, H1975) and squamous cell carcinoma (H520, H292, SW900) NSCLC cells were treated with lonidamine and/or 968 for 72 h under physiological levels of glucose (1.5 mM). Cells were irradiated with 0, 4 or 8 Gy. Cell growth of H2B-mCherry transduced cells and cytotoxicity (CellTox Green Cytotoxicity Assay) were measured using live cell imaging (IncuCyte). Inhibitory effects on metabolic profiles was determined using the Seahorse XF96 extracellular Flux analyzer. RESULTS: NSCLC cell lines responded differently to glycolysis (lonidamine) and/or glutaminase (968) inhibition, largely corresponding with changes in glycolytic and mitochondrial metabolism upon treatment. Response patterns were not related to histology. 968 was cytotoxic in cell lines with high glutaminase C expression (H1975 and H520), whereas combination treatment was cytotoxic in KRAS mutated cell lines SW900 and H23. H292 and HCC827 were resistant to combination treatment. Treatment with 968 and especially lonidamine resulted in radiosensitization of H292 and HCC827 in terms of decreased relative cell growth and increased cytotoxicity. CONCLUSION: NSCLC is a heterogeneous disease, which is reflected in the response of different cell lines to the treatment (combinations) reported here. Only a part of NSCLC patients may benefit from the combination of radiation therapy and metabolic inhibition, making stratification necessary

Epigenetic reader complexes of the human malaria parasite, Plasmodium falciparum

Contains fulltext : 214598.pdf (publisher's version ) (Open Access

Single-cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype.

Basal breast cancer is associated with younger age, early relapse, and a high mortality rate. Here, we use unbiased droplet-based single-cell RNA sequencing (RNA-seq) to elucidate the cellular basis of tumor progression during the specification of the basal breast cancer subtype from the luminal progenitor population in the MMTV-PyMT (mouse mammary tumor virus-polyoma middle tumor-antigen) mammary tumor model. We find that basal-like cancer cells resemble the alveolar lineage that is specified upon pregnancy and encompass the acquisition of an aberrant post-lactation developmental program of involution that triggers remodeling of the tumor microenvironment and metastatic dissemination. This involution mimicry is characterized by a highly interactive multicellular network, with involution cancer-associated fibroblasts playing a pivotal role in extracellular matrix remodeling and immunosuppression. Our results may partially explain the increased risk and poor prognosis of breast cancer associated with childbirth