Sherrie Clark - Profile on Academia.edu (original) (raw)

Papers by Sherrie Clark

Abstract 1456: First successful engraftment of human liver cancer cell line in highly robust immunocompromised porcine model to test the tumor ablation efficacy by histotripsy

Cancer research, Mar 22, 2024

Pharmaceutics, May 24, 2023

Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, d... more Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, dense stroma, and disarrayed vasculature. Ultrasound-induced cavitation is an emerging technology that may overcome many of these limitations. Low-intensity ultrasound, coupled with co-administered cavitation nuclei consisting of gas-stabilizing sub-micron scale SonoTran Particles, is effective at increasing therapeutic antibody delivery to xenograft flank tumors in mouse models. Here, we sought to evaluate the effectiveness of this approach in situ using a large animal model that mimics human pancreatic cancer patients. Immunocompromised pigs were surgically engrafted with human Panc-1 pancreatic ductal adenocarcinoma (PDAC) tumors in targeted regions of the pancreas. These tumors were found to recapitulate many features of human PDAC tumors. Animals were intravenously injected with the common cancer therapeutics Cetuximab, gemcitabine, and paclitaxel, followed by infusion with SonoTran Particles. Select tumors in each animal were targeted with focused ultrasound to induce cavitation. Cavitation increased the intra-tumor concentrations of Cetuximab, gemcitabine, and paclitaxel by 477%, 148%, and 193%, respectively, compared to tumors that were not targeted with ultrasound in the same animals. Together, these data show that ultrasound-mediated cavitation, when delivered in combination with gas-entrapping particles, improves therapeutic delivery in pancreatic tumors under clinically relevant conditions.

Breeding management of small ruminants and camelids

Scientific Reports, Apr 7, 2021

New therapies to treat pancreatic cancer are direly needed. However, efficacious interventions la... more New therapies to treat pancreatic cancer are direly needed. However, efficacious interventions lack a strong preclinical model that can recapitulate patients' anatomy and physiology. Likewise, the availability of human primary malignant tissue for ex vivo studies is limited. These are significant limitations in the biomedical device field. We have developed RAG2/IL2RG deficient pigs using CRISPR/Cas9 as a large animal model with the novel application of cancer xenograft studies of human pancreatic adenocarcinoma. In this proof-of-concept study, these pigs were successfully generated using on-demand genetic modifications in embryos, circumventing the need for breeding and husbandry. Human Panc01 cells injected subcutaneously into the ears of RAG2/IL2RG deficient pigs demonstrated 100% engraftment with growth rates similar to those typically observed in mouse models. Histopathology revealed no immune cell infiltration and tumor morphology was highly consistent with the mouse models. The electrical properties and response to irreversible electroporation of the tumor tissue were found to be similar to excised human pancreatic cancer tumors. The ample tumor tissue produced enabled improved accuracy and modeling of the electrical properties of tumor tissue. Together, this suggests that this model will be useful and capable of bridging the gap of translating therapies from the bench to clinical application.

Quantification of zearalenone and α-zearalenol in swine liver and reproductive tissues using GC-MS

Toxicon: X, Dec 1, 2020

The mycotoxin zearalenone (ZEN) is a common contaminant of swine feed which has been related to a... more The mycotoxin zearalenone (ZEN) is a common contaminant of swine feed which has been related to a wide range of reproductive anomalies in swine, such as pelvic organ prolapse, anestrous, and pseudopregnancy. New information is needed to understand how ZEN and related metabolites accumulate in swine reproductive tissues. We conducted a feeding study to track ZEN and the metabolite α-zearalenol (α-ZEL) in swine liver and reproductive tissues. Thirty pubertal gilts were randomly assigned one of three treatments, with ten pigs in each treatment group: (1) base feed with solvent for 21 days, (2) ZEN-spiked feed for seven days followed by base feed with solvent for 14 days, and (3) ZEN-spiked feed for 21 days. At the end of the trial, liver, anterior vagina, posterior vagina, cervix, uterus, ovaries, and broad ligament were collected from pigs. ZEN was found in the anterior vagina, posterior vagina, cervix, and ovaries, with significantly higher concentrations in the cervix relative to other reproductive tissues. ZEN and α-ZEL were found in liver tissue from pigs in each treatment group. Our results show that ZEN accumulates more in the cervix than other reproductive tissues. The presence of ZEN in reproductive tissues may be indicative of ZEN-related reproductive symptoms. Future work could examine how ZEN concentrations vary in reproductive tissues as a factor of the pigs age, weight, sex, or parity, to establish parameters that make pig more sensitive to ZEN.

In-plane and out-of-plane deformations of gilt utero-sacral ligaments

Journal of The Mechanical Behavior of Biomedical Materials, Jul 1, 2022

Reproductive Biology and Endocrinology, Nov 3, 2016

Background: Pigs with SCID can be a useful model in regenerative medicine, xenotransplantation, a... more Background: Pigs with SCID can be a useful model in regenerative medicine, xenotransplantation, and cancer cell transplantation studies. Utilizing genome editing technologies such as CRISPR/Cas9 system allows us to generate genetically engineered pigs at a higher efficiency. In this study, we report generation and phenotypic characterization of IL2RG knockout female pigs produced through combination of CRISPR/Cas9 system and SCNT. As expected, pigs lacking IL2RG presented SCID phenotype. Methods: First, specific CRISPR/Cas9 systems targeting IL2RG were introduced into developing pig embryos then the embryos were transferred into surrogates. A total of six fetuses were obtained from the embryo transfer and fetal fibroblast cell lines were established. Then IL2RG knockout female cells carrying biallelic genetic modification were used as donor cells for SCNT, followed by embryo transfer. Results: Three live cloned female piglets carrying biallelic mutations in IL2RG were produced. All cloned piglets completely lacked thymus and they had a significantly reduced level of mature T, B and NK cells in their blood and spleen. Conclusions: Here, we generated IL2RG knockout female pigs showing phenotypic characterization of SCID. This IL2RG knockout female pigs will be a promising model for biomedical and translational research.

Pharmaceutics

Animal, 2016

The objective was to determine the effects of immunization against gonadotropin-releasing hormone... more The objective was to determine the effects of immunization against gonadotropin-releasing hormone on reproductive characteristics in boars. A total of 72 boars were used in a randomized design with three treatments: single immunization (SI) (10 weeks of age) or double immunization (DI) (10 and 15 weeks of age) with Improvest® and intact controls (no Improvest®; CNT) (n=24/group). At 10, 15, 20, 25 and 40 weeks of age, blood was collected and serum harvested to evaluate testosterone concentrations. Testosterone concentrations were less for DI boars compared with CNT boars and SI boars at 20 and 25 weeks (P<0.001), but not at 40 weeks of age. At week 25, 18 pigs (n=6/group) were sacrificed and testes were removed, weighed and measured, and seminiferous tubules were examined and scored using histological slides of testes parenchyma. A sample of neck fat was assessed for boar taint aroma. All testicular measurements and weights and seminiferous tubule scores were less for DI boars co...

Clinical signs and rotavirus fecal shedding in AttHRV-vaccinated HGM pigs after VirHRV challenge

aPigs with daily fecal scores of ≥2 were considered diarrheic. Fecal consistency was sco... more aPigs with daily fecal scores of ≥2 were considered diarrheic. Fecal consistency was scored as follows: 0, normal; 1, pasty; 2, semiliquid; and 3, liquid.bFor durations of diarrhea and virus shedding, if no diarrhea or virus shedding until the euthanasia day (PCD7), the duration (days) were recorded as 0 and the onset (days) were as 8 for statistical analysis.cMean cumulative score calculation included all the pigs in each group.dStandard error of the mean.eFFU, fluorescent focus forming units. Geometric mean peak titers were calculated among pigs that shed virus.*Fisher's exact test or ** Kruskal-Wallis rank sum test was used for comparisons. Different letters indicate significant differences among treatment groups (p<0.05), while shared letters indicate no significant difference.</p

Proceedings of the National Academy of Sciences

Hepatitis E virus (HEV) is an important but understudied zoonotic virus causing both acute and ch... more Hepatitis E virus (HEV) is an important but understudied zoonotic virus causing both acute and chronic viral hepatitis. A proportion of HEV-infected individuals also developed neurological diseases such as Guillain–Barré syndrome, neuralgic amyotrophy, encephalitis, and myelitis, although the mechanism remains unknown. In this study, by using an in vitro blood–brain barrier (BBB) model, we first investigated whether HEV can cross the BBB and whether the quasi-enveloped HEV virions are more permissible to the BBB than the nonenveloped virions. We found that both quasi-enveloped and nonenveloped HEVs can similarly cross the BBB and that addition of proinflammatory cytokine tumor necrosis factor alpha (TNF-α) has no significant effect on the ability of HEV to cross the BBB in vitro. To explore the possible mechanism of HEV entry across the BBB, we tested the susceptibility of human brain microvascular endothelial cells lining the BBB to HEV infection and showed that brain microvascular...

In-plane and out-of-plane deformations of gilt utero-sacral ligaments

Journal of the Mechanical Behavior of Biomedical Materials

Breeding management of small ruminants and camelids

Advanced breeding techniques of small ruminants and camelids

Cattle temperament: Effects on health and reproduction

Rotavirus-specific IFN-γ producing T cell responses in HGM transplanted Gn pigs fed with different doses of LGG

Data are presented as mean frequency ± standard error of the mean (n = 4–6). See <a h... more Data are presented as mean frequency ± standard error of the mean (n = 4–6). See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094504#pone-0094504-g002" target="_blank">Fig. 2</a> legend for detection of rotavirus-specific IFN-γ producing T cell and statistical analysis.</p

Treg responses in AttHRV vaccinated pigs with or without HGM transplantation

MNCs were stained freshly without in vitro stimulation. The frequenci... more MNCs were stained freshly without in vitro stimulation. The frequencies of Tregs were expressed as the percentages among gated MNCs (A, top panel). The absolute numbers of Tregs per tissue were calculated based on the frequencies of Tregs and the total number of MNCs isolated from each tissue (A, bottom panel). The frequencies of IL−10+ or TGF−β+ Tregs were expressed as the percentages of IL−10+ or TGF−β+ cells among the Tregs (B). Data are presented as mean number or frequency ± standard error of the mean (n = 4–9). See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094504#pone-0094504-g002" target="_blank">Fig. 2</a> legend for statistical analysis.</p

Number of pigs in non-HGM group and HGM groups at beginning of study and at euthanasia on PID 28 and PCD 7

Number of pigs in non-HGM group and HGM groups at beginning of study and at euthanasia o... more Number of pigs in non-HGM group and HGM groups at beginning of study and at euthanasia on PID 28 and PCD 7.</p

Clinical sign and virus shedding in AttHRV vaccinated pigs with or without HGM transplantation (A) and LGG shedding in fecal samples and large intestinal contents of HGM transplanted Gn pigs fed with or without LGG (B)

After VirHRV challenge, pigs were monitored for 7 days for incidence of diarrhea, fecal ... more After VirHRV challenge, pigs were monitored for 7 days for incidence of diarrhea, fecal score and virus shedding. Data are presented as mean ± standard error of the mean (n = 12 for AttHRV group; n = 4 for HGM+AttHRV group). The sign “*” in (A) indicates significant difference between groups (Kruskal–Wallis test, p<0.05). LGG amounts at different time points were determined by strain-specific real-time PCR and are presented as mean counts/ml ± standard error of the mean (n = 7–10 for fecal samples and n = 3–6 for large intestinal content samples). The sign “*” in (B) indicates significant differences between groups at the same time points and the symbol “Δ” indicates significant increases in LGG numbers compared to PID 5 for the same group (Kruskal–Wallis test, p<0.05).</p

T cell responses in AttHRV vaccinated pigs with or without HGM transplantation

MNCs were stimulated with semi-purified AttHRV antigen in vitro for 1... more MNCs were stimulated with semi-purified AttHRV antigen in vitro for 17 hrs. Brefeldin A was added for the last 5 hrs to block secretion of cytokines produced by the T cells. HRV-specific IFN-γ producing CD4+ and CD8+ T cells was detected by intracellular staining and flow cytometry as we previously described <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094504#pone.0094504-Yuan5" target="_blank">[16]</a>. The frequencies of IFN−γ+CD4+/CD8+ T cells were expressed as percentages among total CD3+ T cells (A and B, middle panel). All mean frequencies are reported after subtraction of the background frequencies. The absolute numbers of CD3+CD4+/CD8+ cells and IFN−γ+CD3+CD4+/CD8+ cells per tissue (A and B, top and bottom panels) were calculated based on the frequencies of CD3+CD4+/CD8+ cells and IFN−γ+CD3+CD4+/CD8+ cells, respectively, and the total number of MNCs isolated from each tissue. Data are presented as mean number or frequency ± standard error of the mean (n = 4–12). The sign “*” indicates the significant difference between groups (Kruskal–Wallis test, p<0.05).</p

Abstract 1456: First successful engraftment of human liver cancer cell line in highly robust immunocompromised porcine model to test the tumor ablation efficacy by histotripsy

Cancer research, Mar 22, 2024

Pharmaceutics, May 24, 2023

Breeding management of small ruminants and camelids

Scientific Reports, Apr 7, 2021

Quantification of zearalenone and α-zearalenol in swine liver and reproductive tissues using GC-MS

Toxicon: X, Dec 1, 2020

In-plane and out-of-plane deformations of gilt utero-sacral ligaments

Journal of The Mechanical Behavior of Biomedical Materials, Jul 1, 2022

Reproductive Biology and Endocrinology, Nov 3, 2016

Pharmaceutics

Animal, 2016

Clinical signs and rotavirus fecal shedding in AttHRV-vaccinated HGM pigs after VirHRV challenge

Proceedings of the National Academy of Sciences

In-plane and out-of-plane deformations of gilt utero-sacral ligaments

Journal of the Mechanical Behavior of Biomedical Materials

Breeding management of small ruminants and camelids

Advanced breeding techniques of small ruminants and camelids

Cattle temperament: Effects on health and reproduction

Rotavirus-specific IFN-γ producing T cell responses in HGM transplanted Gn pigs fed with different doses of LGG

Treg responses in AttHRV vaccinated pigs with or without HGM transplantation

Number of pigs in non-HGM group and HGM groups at beginning of study and at euthanasia on PID 28 and PCD 7

T cell responses in AttHRV vaccinated pigs with or without HGM transplantation