Stacy Higgins

Mersana Therapeutics (United States)

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Darrin D. Stuart

Scorpion Therapeutics (United States)

Vesselina G. Cooke

Novartis (United States)

Lesley A. Mathews Griner

National Center for Advancing Translational Sciences

Jeffrey A. Engelman

Novartis Institutes for BioMedical Research

Paul Fordjour

Boston Biomedical Research Institute

Yuji Mishina

University of Michigan–Ann Arbor

John Green

Boston Biomedical Research Institute

Scott Delach

Boston Biomedical Research Institute

Gwynn Pardee

Novartis (United States)

Ribo Guo

Maternal and Child Health Care Hospital of Bao'an

Cooperative Institutions

University of Arkansas at Fayetteville

Mersana Therapeutics (United States)

Novartis (United States)

Boston Biomedical Research Institute

University of Arkansas System

United States Department of Agriculture

Agricultural Research Service

Texas A&M University

Novartis (Switzerland)

U.S. National Poultry Research Center

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Effect of Aspergillus Meal Prebiotic (Fermacto) on Performance of Broiler Chickens in the Starter Phase and Fed Low Protein Diets

The Journal of Applied Poultry Research (2005)

A. Torres-Rodríguez Claudio Sartor Stacy Higgins A.D. Wolfenden L.R. Bielke

Aspergillus meal is a feed additive used to improve broiler gut health and performance. Trials reported here indicate that Aspergillus meal may offer a protein sparing effect when used with low protein diets. Aspergillus meal might offer better results when the level of protein and amino acids is lower than those recommended by NRC or applied in commercial flocks. Lower levels of protein and amino acids as compared with those recommended by NRC or applied in commercial flocks are also a potential environmental benefit. Thus, low protein diets are of interest and important for feed additive evaluation and animal performance.

Starter

Flock

Prebiotic

10.1093/japr/14.4.665

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Citations (52)

Selection and Application of Bacteriophages for Treating Salmonella enteritidis Infections in Poultry

International Journal of Poultry Science (2007)

Stacy Higgins J.P. s Higgin L.R. Bielke Billy M. Hargis

The objective of this study was to select appropriate bacteriophages that survive in the gastrointestinal tract of neonatal poultry and utilize those bacteriophages to reduce intestinal colonization of Salmonella enteritidis phage type 13A (SE) in challenged birds. Broiler chicks served as an in vivo biological filter to preferentially select bacteriophages from our bacteriophage library capable of surviving the gastrointestinal environment. A mixture of bacteriophage isolates designated PHL 1-71 was administered orally to three SE challenged chicks on three consecutive days. Each day, bacteriophages were recovered from the ileum, ileocecal junction and ceca for sequential administration the following day. The recovered bacteriophages were then administered to SE-infected turkey poults. In the first experiment, two-day old poults were challenged with 10 cfu SE and treated 48 h later with 5mM Mg (OH) followed by 2.5×10 plaque 4 9 2 forming units (pfu) of bacteriophages in 1mM Mg (OH) solution. This treatment numerically reduced SE 2 recovered from cecal contents at 12 and 24 h after treatment as compared to untreated controls. In a second experiment, two-day old poults were challenged with 1.6×10 cfu SE and treated with 5mM Mg (OH) followed 4 2 by 7.5×10 pfu phage in 1mM Mg (OH) solution 48 h post-challenge. We recovered 79,728 cfu of SE per g 9 2 of cecal contents in the control group and 11,224 cfu/g in the phage treated group 24 h post treatment. These data were not significantly different, but they suggest that bacteriophages can be preferentially selected in vivo to increase survival in the avian gastrointestinal tract. However, improved efficacy is required prior to useful application of the approach for reducing Salmonella infection.

Salmonella enteritidis

10.3923/ijps.2007.163.168

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Citations (28)

Figure S1 from LXH254, a Potent and Selective ARAF-Sparing Inhibitor of BRAF and CRAF for the Treatment of MAPK-Driven Tumors

Kelli‐Ann Monaco Scott Delach Jing Yuan Yuji Mishina Paul Fordjour

<p>Supplementary Figure 1. Shown in (A) are the IC50 values for the inhibition of proliferation for BRAF ( ), KRAS ( ), and NRAS ( ) mutant as well as "WT" ( ) cell lines. Below the graph Fischer's exact test using 1, 2, and 2.5ï�M sensitivity cutoffs are provided. (B) Comparison of cell line sensitivities for LXH254 and RAF709. LXH254 values are provided in this manuscript (Sup. Table 3) and RAF709 values obtained from (25). (C) mRNA expression (RNASeq, https://portals.broadinstitute.org/ccle/data) for cell lines presented in (A) with the 2.0ï�M LXH254 sensitivity threshold delineated. (D) ARAF mRNA expression in KRAS mutant and wild type cells from TCGA Pan-cancer Atlas Project (47), using the cBIO cancer genomics portal (https://www.cbioportal.org/, (1,2))</p>

10.1158/1078-0432.22480689

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Table S2 from LXH254, a Potent and Selective ARAF-Sparing Inhibitor of BRAF and CRAF for the Treatment of MAPK-Driven Tumors

Kelli‐Ann Monaco Scott Delach Jing Yuan Yuji Mishina Paul Fordjour

<p>Results of Kinativ studies using LXH254 in HCT 116 cells</p>

Table (database)

10.1158/1078-0432.22480668

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Table S7 from LXH254, a Potent and Selective ARAF-Sparing Inhibitor of BRAF and CRAF for the Treatment of MAPK-Driven Tumors

Kelli‐Ann Monaco Scott Delach Jing Yuan Yuji Mishina Paul Fordjour

<p>In vivo anti-tumor effects of LXH254 and Trametinib</p>

Trametinib

10.1158/1078-0432.22480653.v1

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Data from Discovery and Preclinical Characterization of XMT-1660, an Optimized B7-H4-Targeted Antibody–Drug Conjugate for the Treatment of Cancer

Dorin Toader Shawn P. Fessler Scott D. Collins Patrick R. Conlon Reddy Bollu

<div>Abstract<p>Antibody-drug conjugates (ADCs) achieve targeted drug delivery to a tumor and have demonstrated clinical success in many tumor types. The activity and safety profile of an ADC depends on its construction: antibody, payload, linker, and conjugation method, as well as the number of payload drugs per antibody (drug-to-antibody ratio, DAR). To allow for ADC optimization for a given target antigen, we developed Dolasynthen, a novel ADC platform based on the payload auristatin hydroxypropylamide (AF-HPA), that enables precise DAR-ranging and site-specific conjugation. We used the new platform to optimize an ADC that targets B7-H4 (VTCN1), an immune-suppressive protein that is overexpressed in breast, ovarian, and endometrial cancers. XMT-1660 is a site-specific Dolasynthen DAR 6 ADC that induced complete tumor regressions in xenograft models of breast and ovarian cancer as well as in a syngeneic breast cancer model that is refractory to PD-1 immune checkpoint inhibition. In a panel of 28 breast cancer patient-derived xenografts (PDX), XMT-1660 demonstrated activity that correlated with B7-H4 expression. XMT-1660 has recently entered clinical development in a Phase 1 study (NCT05377996) in cancer patients.</p></div>

Antibody-drug conjugate

Conjugate

10.1158/1535-7163.c.6821443

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Citations (0)

Data from Discovery and Preclinical Characterization of XMT-1660, an Optimized B7-H4-Targeted Antibody–Drug Conjugate for the Treatment of Cancer

Dorin Toader Shawn P. Fessler Scott D. Collins Patrick R. Conlon Reddy Bollu

<div>Abstract<p>Antibody–drug conjugates (ADC) achieve targeted drug delivery to a tumor and have demonstrated clinical success in many tumor types. The activity and safety profile of an ADC depends on its construction: antibody, payload, linker, and conjugation method, as well as the number of payload drugs per antibody [drug-to-antibody ratio (DAR)]. To allow for ADC optimization for a given target antigen, we developed Dolasynthen (DS), a novel ADC platform based on the payload auristatin hydroxypropylamide, that enables precise DAR-ranging and site-specific conjugation. We used the new platform to optimize an ADC that targets B7-H4 (<i>VTCN1</i>), an immune-suppressive protein that is overexpressed in breast, ovarian, and endometrial cancers. XMT-1660 is a site-specific DS DAR 6 ADC that induced complete tumor regressions in xenograft models of breast and ovarian cancer as well as in a syngeneic breast cancer model that is refractory to PD-1 immune checkpoint inhibition. In a panel of 28 breast cancer PDXs, XMT-1660 demonstrated activity that correlated with B7-H4 expression. XMT-1660 has recently entered clinical development in a phase I study (NCT05377996) in patients with cancer.</p></div>

Antibody-drug conjugate

Conjugate

10.1158/1535-7163.c.6821443.v1

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Citations (0)

Temporal Effects of Lactic Acid Bacteria Probiotic Culture on Salmonella in Neonatal Broilers

Poultry Science (2007)

Jack P. Higgins Stacy Higgins J.L. Vicente A.D. Wolfenden Guillermo Téllez–Isaías

We evaluated the ability of a commercially available lactic acid bacteria-based probiotic culture (LAB) to reduce Salmonella Enteritidis or Salmonella Typhimurium in day-of-hatch broiler chicks. In these experiments, chicks were challenged with Salmonella Enteritidis or Salmonella Typhimurium and treated with LAB 1-h postchallenge. Following treatment, cecal tonsils and ceca were aseptically collected for Salmonella Enteritidis or Salmonella Typhimurium enrichment or Salmonella Enteritidis enumeration, respectively. In experiments 1 to 3, LAB significantly reduced the incidence of Salmonella Enteritidis (60 to 70% reduction) or Salmonella Typhimurium (89 to 95% reduction) recovered from the cecal tonsils of day-old broiler chicks 24 h following treatment as compared with controls (P < 0.05). Additionally, administration of LAB caused a >2.9 log10 reduction of total cecal Salmonella Enteritidis recovered 24 h following treatment as compared with controls (P < 0.05). In experiments 4 to 7, upon sample enrichment LAB significantly reduced the recovery of Salmonella Enteritidis from the cecal tonsils at 24 h, but not 6 or 12 h posttreatment (P < 0.05). However, in experiments 6 and 7, when total cecal Salmonella Enteritidis recovery was enumerated, a significant treatment-associated reduction was observed 12 h posttreatment, although in cecal tonsil samples there was no difference in Salmonella Enteritidis incidence at 12 h (P < 0.05). In these studies, LAB treatment significantly reduced recovery of Salmonella in day-of-hatch broilers.

Salmonella enteritidis

Cecum

10.1093/ps/86.8.1662

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Citations (155)

Effects of Lime on Salmonella enteritidis Survival In Vitro

The Journal of Applied Poultry Research (2003)

Dwayne Bennett Stacy Higgins R.W. Moore R. Beltran Daniel J. Caldwell

The presence of Salmonella or Campylobacter in poultry litter may contribute to contaminated processed carcasses by increasing the bacterial load of skin and feathers or by providing a source for upper gastrointestinal contamination during preharvest feed withdrawal. Presently, we evaluated the effect of added lime on survival of Salmonella enteritidis in used poultry litter during room temperature incubations for 24, 48, or 96 h. Addition of any concentration of lime evaluated markedly increased pH (control: 8.36; 5%: 12.13; 10%: 12.53; 20%: 12.57). Addition of lime resulted in significantly reduced Salmonella recovery incidence at 24 h. Interestingly, no further lime-associated reduction in Salmonella recovery was observed at 48 h. These data suggest that the addition of hydrated lime can markedly reduce Salmonella recovery in a relatively short time (<24 h). The effect and persistence of lime-associated pH elevations under commercial conditions remains to be evaluated.

Preharvest

Salmonella enteritidis

Litter

10.1093/japr/12.1.65

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Citations (47)

Effect of Lactose as a Prebiotic on Turkey Body Weight Under Commercial Conditions

The Journal of Applied Poultry Research (2007)

A. Torres-Rodríguez Stacy Higgins J.L. Vicente A.D. Wolfenden G. Gaona-Ramírez

The effect of a commercially available lactic acid bacteria probiotic (FM-B11) alone and supplemented with lactose as prebiotic was evaluated for effects on turkey BW during the brooding and growout phases under commercial conditions in 2 experiments. Tag-numbered turkey poults were given the probiotic in either drinking water or feed, and lactose was given in feed. Turkeys were reared in wire pens (4 per treatment) within the brooding house. Experiments were designed for a duration of 26 and 28 d. Only animals from experiment 1 were weighed again before slaughter. Results from both experiments indicate that groups treated with the combination of probiotic and lactose and lactose alone were heavier (P < 0.05) by 15.5 and 17.5% in experiments 1 and 2, respectively, as compared with the control groups. Market BW of turkeys from experiment 1 was higher (P < 0.05) with the combination of probiotic and lactose than the control group by 436 g. Turkeys on the probiotic alone tended to be heavier than the controls (P = 0.0693). The administration of this lactic acid bacteria-based probiotic, supplemented with lactose as prebiotic to turkey poults during the brooding phase, increased BW, and this advantage was further maintained or augmented during the growout phase.

Prebiotic

10.3382/japr.2006-00127

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Citations (41)