Biomedical Valley Discoveries

Valley Park, MO, United States

Biomedical Valley Discoveries

Valley Park, MO, United States

Time filter

Source Type

"The MAPK signaling pathway is canonical and controls cell growth, proliferation, and survival. It has aberrant signaling activity in many cancer types due to a very large number of mutations of diverse types. Because of its importance, the MAPK pathway has been at the focus of drug discovery and development for many years" said Michael Vidne, PhD, Chief Commercial Officer at NovellusDx. "We are happy that we are able to accelerate the drug development and potentially help it reach more patients with our novel, live-cell based assay to monitor the activity of mutations and their response to drugs." About BioMed Valley Discoveries BioMed Valley Discoveries is a clinical stage biotechnology company focused on addressing unmet medical needs in a variety of therapeutic and diagnostic areas. In addition to the ERK inhibitor, BVD's portfolio includes an oncolytic bacteria that has completed enrollment for Phase I, a selective phosphoinositide 3-kinase gamma inhibitor in late preclinical testing, and two early-stage antibodies targeting the tumor microenvironment. Operating since 2007, BioMed Valley Discoveries was established by Jim Stowers Jr., founder of the asset management firm American Century Investments, and his wife Virginia, to advance new medical innovations to improve the lives of patients with difficult-to-treat diseases. BVD is owned by a supporting organization of the Stowers Institute for Medical Research, a non-profit, basic biomedical research organization. Profits from BioMed Valley Discoveries accrue to the benefit of the Stowers Institute. About NovellusDx NovellusDx' mission is to provide functional information about mutations and their responses to drugs, so that oncologists can treat patients with precision therapies, and bio-pharmaceutical companies can develop drugs more effectively. NovellusDx approach is to monitor the functional effects of mutations and observe the effects of drugs, drug combinations and drug candidates on the activity level caused by the mutations. NovellusDx headquarters and R&D are based in in Jerusalem, Israel. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/novellusdx-announced-today-the-completion-of-the-first-phase-of-an-in-vitro-study-of-biomed-valley-discoveries-bvd523-300477098.html


Zheng L.,Shanghai JiaoTong University | Zheng L.,Northwestern University | Zhang Z.,Northwestern University | Zhang Z.,Robert rie Comprehensive Cancer Center | And 6 more authors.
PLoS ONE | Year: 2014

Objectives: To validate the feasibility of labeling Clostridium novyi-NT (C.novyi-NT) anaerobes with iron-oxide nanoparticles for magnetic resonance imaging (MRI) and demonstrate the potential to use MRI to visualize intra-tumoral delivery of these iron-oxide labeled C.novyi-NT during percutaneous injection procedures. Materials and Methods: All studies were approved by IACUC. C.novyi-NT were labeled with hybrid iron-oxide Texas red nanoparticles. Growth of labeled and control samples were evaluated with optical density. Labeling was confirmed with confocal fluorescence and transmission electron microscopy (TEM). MRI were performed using a 7 Tesla scanner with T2∗-weighted (T2∗W) sequence. Contrast-to-noise ratio (CNR) measurements were performed for phantoms and signal-to-noise ratio (SNR) measurements performed in C57BL/6 mice (n=12) with Panc02 xenografts before and after percutaneous injection of iron-oxide labeled C.novyi-NT. MRI was repeated 3 and 7 days post-injection. Hematoxylin-eosin (HE), Prussian blue and Gram staining of tumor specimens were performed for confirmation of intra-tumoral delivery. Results: Iron-oxide labeling had no influence upon C.novyi-NT growth. The signal intensity (SI) within T2∗W images was significantly decreased for iron-oxide labeled C.novyi-NT phantoms compared to unlabeled controls. Under confocal fluorescence microscopy, the iron-oxide labeled C.novyi-NT exhibited a uniform red fluorescence consistent with observed regions of DAPI staining and overall labeling efficiency was 100% (all DAPI stained C.novyi-NT exhibited red fluorescence). Within TEM images, a large number iron granules were observed within the iron-oxide labeled C.novyi-NT; these were not observed within unlabeled controls. Intraprocedural MRI measurements permitted in vivo visualization of the intra-tumoral distribution of iron-oxide labeled C.novyi-NT following percutaneous injection (depicted as punctate regions of SI reductions within T2∗-weighted images); tumor SNR decreased significantly following intra-tumoral injection of C.novyi-NT (p<0.05); these SNR reductions were maintained at 3 and 7 day follow-up intervals. Prussian blue and Gram staining confirmed presence of the iron-oxide labeled anaerobes. Conclusions: C.novyi-NT can be labeled with iron-oxide nanoparticles for MRI visualization of intra-tumoral deposition following percutaneous injection during bacteriolytic therapy. © 2014 Zheng et al.


PubMed | Shanghai JiaoTong University, Biomedical Valley Discoveries, Northwestern University and Rochester College
Type: Journal Article | Journal: PloS one | Year: 2014

To validate the feasibility of labeling Clostridium novyi-NT (C.novyi-NT) anaerobes with iron-oxide nanoparticles for magnetic resonance imaging (MRI) and demonstrate the potential to use MRI to visualize intra-tumoral delivery of these iron-oxide labeled C.novyi-NT during percutaneous injection procedures.All studies were approved by IACUC. C.novyi-NT were labeled with hybrid iron-oxide Texas red nanoparticles. Growth of labeled and control samples were evaluated with optical density. Labeling was confirmed with confocal fluorescence and transmission electron microscopy (TEM). MRI were performed using a 7 Tesla scanner with T2*-weighted (T2*W) sequence. Contrast-to-noise ratio (CNR) measurements were performed for phantoms and signal-to-noise ratio (SNR) measurements performed in C57BL/6 mice (n=12) with Panc02 xenografts before and after percutaneous injection of iron-oxide labeled C.novyi-NT. MRI was repeated 3 and 7 days post-injection. Hematoxylin-eosin (HE), Prussian blue and Gram staining of tumor specimens were performed for confirmation of intra-tumoral delivery.Iron-oxide labeling had no influence upon C.novyi-NT growth. The signal intensity (SI) within T2*W images was significantly decreased for iron-oxide labeled C.novyi-NT phantoms compared to unlabeled controls. Under confocal fluorescence microscopy, the iron-oxide labeled C.novyi-NT exhibited a uniform red fluorescence consistent with observed regions of DAPI staining and overall labeling efficiency was 100% (all DAPI stained C.novyi-NT exhibited red fluorescence). Within TEM images, a large number iron granules were observed within the iron-oxide labeled C.novyi-NT; these were not observed within unlabeled controls. Intra-procedural MRI measurements permitted in vivo visualization of the intra-tumoral distribution of iron-oxide labeled C.novyi-NT following percutaneous injection (depicted as punctate regions of SI reductions within T2*-weighted images); tumor SNR decreased significantly following intra-tumoral injection of C.novyi-NT (p<0.05); these SNR reductions were maintained at 3 and 7 day follow-up intervals. Prussian blue and Gram staining confirmed presence of the iron-oxide labeled anaerobes.C.novyi-NT can be labeled with iron-oxide nanoparticles for MRI visualization of intra-tumoral deposition following percutaneous injection during bacteriolytic therapy.


Tung D.,Biomedical Valley Discoveries | Ciallella J.,Melior Discovery, Inc. | Hain H.,Melior Discovery, Inc. | Cheung P.H.,Biomedical Valley Discoveries | Saha S.,Biomedical Valley Discoveries
Current Therapeutic Research - Clinical and Experimental | Year: 2013

Background: Trilostane was identified in an in vivo screen of compounds in a lipopolysaccharide model of inflammation to support a repurposing effort. There is no previous documentation of any anti-inflammatory effects of trilostane. Objective: The aim of this study was to elucidate the novel pharmacologic activity of trilostane in a series of inflammation and nociception signal-finding models. Methods: Anti-inflammatory effects of trilostane were evaluated in lipopolysaccharide-induced systemic and lung inflammation models and in a 2,4-dinitrofluorobenzene-induced delayed-type hypersensitivity (DTH) model in the mouse ear. The analgesic activities of trilostane were evaluated in a hot plate nociception model as a function of paw-withdrawal latency and in the formalin-induced nociception model with a behavioral end point. In all studies, trilostane was administered 15 minutes before challenge. In the DTH model, the animals were given a second dose 24 hours after the first dose. Results: Trilostane inhibited tumor necrosis factor-α and monocyte chemoattractant protein-1 production in the lipopolysaccharide-induced systemic and pulmonary inflammation models. It also significantly reduced ear swelling in the 2,4-dinitrofluorobenzene-induced DTH model. In the hot plate nociception model, trilostane increased the latency of paw-licking behavior. Trilostane also significantly reduced the duration of pain behaviors in the late phase of the formalin-induced inflammatory pain model. Conclusions: These signal-finding studies suggest that trilostane has novel anti-inflammatory and analgesic properties. © 2013 The Authors.


Tung D.,Biomedical Valley Discoveries | DeCrescenzo G.,Biomedical Valley Discoveries | Welsch D.,Biomedical Valley Discoveries | Cheung P.H.,Biomedical Valley Discoveries | And 2 more authors.
World Journal of Microbiology and Biotechnology | Year: 2014

The nucleoside analogue, 1-(2-deoxy-2-fluoro-1-d-arabinofuranosyl)-5-iodouracil (FIAU) is a substrate for thymidine kinase (TK), which is commonly expressed in bacteria. It is currently being investigated in clinical studies as an in vivo bacterial infection detection agent. In developing countries where imaging facilities are not readily available, deploying such technology can be a big hurdle. However, a portable ex vivo system might provide a good alternative. In an in vitro system, [125I]-FIAU incubated with bacteria is phosphorylated by TK, and is trapped within the bacteria, which can be detected by radioscintography. The suitability of this agent to be utilized as part of an ex vivo bacterial detection system was evaluated. In the first part of this report, the optimization of the incubation and detection condition using E. coli as a test case is described. Samples were incubated in a growth promoting medium containing the label, then after filtering and washing, the amount of radioactivity trapped on the filter was quantitated by a scintillation counter. As a proof of concept demonstration, blinded urine samples from urinary tract infection (UTI) patients and normal donors were tested in the FIAU system. Of the 13 UTI positive and 15 normal urine samples tested, there were 2 false negatives and 1 false positive, respectively. Potential explanations for the false positive and negatives as well as the commercialization possibility of this system will be discussed. © 2014, Springer Science+Business Media Dordrecht.


Morgen M.,Bend Research Inc. | Tung D.,Biomedical Valley Discoveries | Boras B.,University of California at San Diego | Miller W.,Bend Research Inc. | And 2 more authors.
Pharmaceutical Research | Year: 2013

Purpose: To evaluate using cationic polymeric nanoparticles that interact with hyaluronate to form ionically cross-linked hydrogels to increase the intra-articular retention time of osteoarthritis drugs in the synovial cavity. Methods: In vitro tests included nanoparticle release from cross-linked hydrogels using syringe and membrane dissolution tests, viscosity measurement of synovial fluid containing hydrogels, and release-rate measurement for a model active conjugated to a cationically substituted dextran using a hydrolyzable ester linkage in a sink dissolution test. Nanoparticle retention after intra-articular injection into rat knees was measured in vivo using fluorescence molecular tomography. Results: Diffusional and convective transport of cationic nanoparticles from ionically cross-linked hydrogels formed in synovial fluid was slower in vitro than for uncharged nanoparticles. Hydrogels formed after the nanoparticles were mixed with synovial fluid did not appreciably alter the viscosity of the synovial fluid in vitro. In vitro release of a conjugated peptide from the cationic nanoparticles was approximately 20% per week. After intra-articular injection in rat knees, 70% of the nanoparticles were retained in the joint for 1 week. Conclusions: This study demonstrates the feasibility of using cationic polymeric nanoparticles to increase the retention of therapeutic agents in articular joints for indications such as osteoarthritis. © The Author(s) 2012.


Tung D.,Biomedical Valley Discoveries | Cheung P.H.,Biomedical Valley Discoveries | Tudor G.,Epistem Ltd | Booth C.,Epistem Ltd | Saha S.,Biomedical Valley Discoveries
Current Therapeutic Research - Clinical and Experimental | Year: 2011

Background: Fluorouracil (5-FU) is a pyrimidine analogue used as a cancer treatment. Its toxic side effects, including mucositis, are reported to occur in 40% of the treated patients. Because of the inflammatory component of mucositis, we explored the possibility of modulating this condition with an immunomodulatory agent and a tumor necrosis factor-α inhibitor. Objective: The aim of this study was to evaluate the effect of 2 immunosuppressive agents, etanercept and cyclosporine, in a murine model of 5-FU-induced mucositis. Methods: To study the short-term effects of 5-FU on mucositis, cyclosporine and etanercept were administered to mice after an injection of 5-FU. The animals (n = 8) were euthanized at 6 hours post-challenge. Hematoxylin and eosin-stained histologic sections of the small intestine were examined for signs of apoptosis. To further examine the potential of cyclosporine in the treatment of 5-FU-induced mucositis in a longer duration, the animals (N = 15) were given 2 challenges of 5-FU within 6 hours. All mice were dosed daily until day 9 with either cyclosporine (100 mg/kg) or phosphate-buffered saline (PBS). Results: Six hours after 5-FU challenge, 25 mg/kg etanercept and 50 mg/kg cyclosporine had no effect on 5-FU-induced apoptosis (P > 0.05). However, 100 mg/kg cyclosporine significantly reduced the cumulative level of apoptosis >41.6% of the intestinal crypt surface (P < 0.05). During long-term observation, all mice began to lose weight at a rate of approximately 0.8 g/day after 5-FU exposure. The rates of weight loss and survival were not affected by cyclosporine treatment. The diarrhea onset began on day 4 with 46.7% of the PBS-treated mice showing signs of diarrhea compared with 53.3% in the cyclosporine group. The diarrhea score for both groups plateaued on day 7, with a cumulative score of 41 for the PBS group and 50 for the cyclosporine group. Cyclosporine treatment did not affect the diarrhea onset day or severity compared with the PBS-treated group (P > 0.05). Conclusions: Our data indicated that etanercept is not a suitable treatment for 5-FU-induced mucositis. Despite decreased apoptosis in the gut, cyclosporine did not affect the severity of the diarrhea or survival. Therefore, we concluded that cyclosporine treatment was only effective in mediating the short-term apoptotic events in the intestines but has no long-term effect on the animals' survival and diarrhea. © 2011 Elsevier HS Journals, Inc.


PubMed | Biomedical Valley Discoveries
Type: Journal Article | Journal: Pharmacology | Year: 2011

Repaglinide is an FDA-approved treatment for type 2 diabetes mellitus. The anti-inflammatory effect of repaglinide in the absence of diabetes has not been reported previously. It is the objective of this set of studies to investigate the potential anti-inflammatory effects of repaglinide.The in vivo anti-inflammatory effects of repaglinide were studied in two different models of delay type hyperreactivity (DTH) response induced by sheep red blood cells (sRBC) and 2,5-dinitrofluorobenzene (DNFB), and in two different rodent models of lipopolysaccharide (LPS) challenge.In mice systemically sensitized with sRBC, which subsequently received a local injection of sRBC in the footpad, local swelling occurred within 24 h after challenge. Repaglinide was efficacious in attenuating this response. In an orthogonal DTH model using DNFB as the antigen, the animals received topical sensitization with DNFB on their shaved backs, followed by topical challenge on the left ears. Repaglinide efficaciously downregulated the resulting ear swelling response. In mice challenged systemically or intratracheally with LPS, repaglinide significantly decreased serum tumor necrosis factor level and bronchial alveolar lavage fluid MCP-1 levels, respectively.This set of data suggests novel anti-inflammatory effects of repaglinide in nondiabetic animals. However, the high dose required for an efficacious effect would make this application impractical in the clinic.


PubMed | Biomedical Valley Discoveries
Type: Journal Article | Journal: Pharmacology | Year: 2013

Doxazosin is an (1)-adrenergic receptor antagonist for the treatment of high blood pressure and benign prostatic hyperplasia. Peripheral -adrenergic receptors have been implicated in inflammation.To examine the anti-inflammatory effects of doxazosin in rodent models of inflammation.The anti-inflammatory properties of doxazosin were investigated in 4 models. In all studies, drug treatment was administered 15 min prior to challenge. In the lipopolysaccharide (LPS)-induced systemic inflammation model, LPS was injected systemically at 0.25 mg/kg. At 90 min after challenge, blood samples were collected for analysis. In the LPS-induced pulmonary inflammation model, LPS was instilled intranasally. Four hours after challenge, the lungs were harvested for monocyte chemoattractant protein-1 (MCP-1) analysis. In a delayed-type hypersensitivity model, the mice were injected intravenously with sheep red blood cells, and rechallenged in the left footpad 7 days later. Drug treatment was given on day 6 and 7 just prior to the rechallenge. The thickness of hind footpads was measured at 15 min after rechallenge. In the thioglycollate-induced peritoneal monocyte infiltration model, mice were challenged with 3% thioglycollate, and 2 h later peritoneal lavage fluid was collected for MCP-1 analysis.In animals challenged systemically and intranasally with LPS, doxazosin inhibited TNF- and MCP-1 production, respectively. In the delayed-type hypersensitivity model, footpad swelling was inhibited by doxazosin. Doxazosin decreased the level of MCP-1 release in the peritoneal cavity of thioglycollate-stimulated animals, though this effect was not statistically significant.This is the first set of studies that reports the novel anti-inflammatory effects of doxazosin.


PubMed | Biomedical Valley Discoveries
Type: Journal Article | Journal: Pharmacology | Year: 2011

Bortezomib (Velcade) is a proteasome inhibitor that has been approved for the treatment of multiple myeloma and mantle cell lymphoma. It has been shown to inhibit the expression of cell adhesion molecules, co-stimulatory molecules, and NFB activation, to deplete alloreactive T lymphocytes, and to decrease Th1 cytokine production. The anti-inflammatory effects of bortezomib were further investigated in this current set of studies. Systemic treatment with bortezomib was efficacious in the thioglycolate-induced MCP-1 production model, and the dinitrofluorobenzene-induced delayed-type hypersensitivity model. Psoriasis is an autoimmune disease that affects about 2% of the world population. Many treatments have been reported with varying degrees of efficacy. A topical bortezomib formulation was developed to minimize systemic exposure. Its tolerability was investigated in a topical imiquimod (IMQ)-induced psoriasis model. Daily application of IMQ on mouse skin induced inflamed scaly skin lesions resembling plaque-type psoriasis. Fatality was observed in the 1-mg/ml dose group. At 0.1 and 0.01 mg/ml, bortezomib potentiated IMQ-induced erythema, scaling, skin thickening, and caused necrotic lesions. Lower doses had no effect on the clinical observations. Histologically, bortezomib dose-dependently increased parakeratosis, hyperkeratosis, acanthosis, and inflammatory cell infiltration. This study demonstrated that topical bortezomib is not suitable for the treatment of psoriasis.

Loading Biomedical Valley Discoveries collaborators
Loading Biomedical Valley Discoveries collaborators