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Article: A Metagenomic Meta-analysis Reveals Functional Signatures of Health and Disease in the Human Gut Microbiome.

Armour, Courtney R / Nayfach, Stephen / Pollard, Katherine S / Sharpton, Thomas J

mSystems

2019 Volume 4, Issue 4

Abstract: While recent research indicates that human health is affected by the gut microbiome, the functional mechanisms that underlie host-microbiome interactions remain poorly resolved. Metagenomic clinical studies can address this problem by revealing specific ... ...

Abstract	While recent research indicates that human health is affected by the gut microbiome, the functional mechanisms that underlie host-microbiome interactions remain poorly resolved. Metagenomic clinical studies can address this problem by revealing specific microbial functions that stratify healthy and diseased individuals. To improve our understanding of the relationship between the gut microbiome and health, we conducted the first integrative functional analysis of nearly 2,000 publicly available fecal metagenomic samples obtained from eight clinical studies. We identified characteristics of the gut microbiome that associate generally with disease, including functional alpha-diversity, beta-diversity, and beta-dispersion. Using regression modeling, we identified specific microbial functions that robustly stratify diseased individuals from healthy controls. Many of these functions overlapped multiple diseases, suggesting a general role in host health, while others were specific to a single disease and may indicate disease-specific etiologies. Our results clarify potential microbiome-mediated mechanisms of disease and reveal features of the microbiome that may be useful for the development of microbiome-based diagnostics.
Language	English
Publishing date	2019-05-14
Publishing country	United States
Document type	Journal Article
ISSN	2379-5077
ISSN	2379-5077
DOI	10.1128/mSystems.00332-18
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Article: A Rare Case of Unresectable Adenoid Cystic Carcinoma of the Nasopharynx Treated with Intensity Modulated Proton Therapy.

Phan, Jae / Ng, Sweet Ping / Pollard, Courtney / Phan, Jack

Cureus

2017 Volume 9, Issue 9, Page(s) e1688

Abstract: Adenoid cystic carcinoma (ACC) is generally treated with surgical resection followed by postoperative radiotherapy. In cases where surgical management is precluded due to the location of the tumor and/or patient factors, radiation therapy can be offered ... ...

Abstract	Adenoid cystic carcinoma (ACC) is generally treated with surgical resection followed by postoperative radiotherapy. In cases where surgical management is precluded due to the location of the tumor and/or patient factors, radiation therapy can be offered to achieve local control. Here, we present a case of unresectable Stage T4N0 ACC of the nasopharynx with skull base and intracranial extension treated with intensity modulated proton therapy (IMPT), which achieved good local control with no significant late toxicity.
Language	English
Publishing date	2017-09-15
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.1688
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Article: Spontaneous seromuscular laceration of the sigmoid colon: a case report.

Pollard, Courtney / Fransman, Ryan B / Jessie, Timothy A / Gurfinchel, Gregory

Clinical case reports

2015 Volume 3, Issue 12, Page(s) 1007–1011

Abstract: Injury to bowel can result in high morbidity and death. Bowel injuries typically occur after external trauma to the abdomen. Bowel injury in the absence of external trauma is rare. Here, we report a 36-year-old male presenting with a sigmoid colon ... ...

Abstract	Injury to bowel can result in high morbidity and death. Bowel injuries typically occur after external trauma to the abdomen. Bowel injury in the absence of external trauma is rare. Here, we report a 36-year-old male presenting with a sigmoid colon laceration likely due to long-standing constipation.
Language	English
Publishing date	2015-11-02
Publishing country	England
Document type	Case Reports
ZDB-ID	2740234-4
ISSN	2050-0904
ISSN	2050-0904
DOI	10.1002/ccr3.396
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Article ; Online: Disruption of a ∼23-24 nucleotide small RNA pathway elevates DNA damage responses in

Lee, Suzanne R / Pollard, Daniel A / Galati, Domenico F / Kelly, Megan L / Miller, Brian / Mong, Christina / Morris, Megan N / Roberts-Nygren, Kerry / Kapler, Geoffrey M / Zinkgraf, Matthew / Dang, Hung Q / Branham, Erica / Sasser, Jason / Tessier, Erin / Yoshiyama, Courtney / Matsumoto, Maya / Turman, Gaea

Molecular biology of the cell

2021 Volume 32, Issue 15, Page(s) 1335–1346

Abstract: Endogenous RNA interference (RNAi) pathways regulate a wide range of cellular processes in diverse eukaryotes, yet in the ciliated eukaryote, ...

Abstract	Endogenous RNA interference (RNAi) pathways regulate a wide range of cellular processes in diverse eukaryotes, yet in the ciliated eukaryote,
MeSH term(s)	DNA/metabolism ; DNA Breaks, Double-Stranded ; DNA Repair ; Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation ; Protozoan Proteins ; RNA, Small Interfering/metabolism ; Rad51 Recombinase/genetics ; Recombinational DNA Repair ; Sequence Analysis, RNA ; Tetrahymena thermophila/genetics ; Tetrahymena thermophila/metabolism
Chemical Substances	Protozoan Proteins ; RNA, Small Interfering ; DNA (9007-49-2) ; Rad51 Recombinase (EC 2.7.7.-)
Language	English
Publishing date	2021-05-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1098979-1
ISSN	1939-4586 ; 1059-1524
ISSN (online)	1939-4586
ISSN	1059-1524
DOI	10.1091/mbc.E20-10-0631
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Zs.A 2853: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression.

Kohlmeyer, Jordan L / Lingo, Joshua J / Kaemmer, Courtney A / Scherer, Amanda / Warrier, Akshaya / Voigt, Ellen / Raygoza Garay, Juan A / McGivney, Gavin R / Brockman, Qierra R / Tang, Amy / Calizo, Ana / Pollard, Kai / Zhang, Xiaochun / Hirbe, Angela C / Pratilas, Christine A / Leidinger, Mariah / Breheny, Patrick / Chimenti, Michael S / Sieren, Jessica C /

Monga, Varun / Tanas, Munir R / Meyerholz, David K / Darbro, Benjamin W / Dodd, Rebecca D / Quelle, Dawn E

Clinical cancer research : an official journal of the American Association for Cancer Research

2023 Volume 29, Issue 17, Page(s) 3484–3497

Abstract: Purpose: Malignant peripheral nerve sheath tumors (MPNST) are lethal, Ras-driven sarcomas that lack effective therapies. We investigated effects of targeting cyclin-dependent kinases 4 and 6 (CDK4/6), MEK, and/or programmed death-ligand 1 (PD-L1) in ... ...

Abstract	Purpose: Malignant peripheral nerve sheath tumors (MPNST) are lethal, Ras-driven sarcomas that lack effective therapies. We investigated effects of targeting cyclin-dependent kinases 4 and 6 (CDK4/6), MEK, and/or programmed death-ligand 1 (PD-L1) in preclinical MPNST models. Experimental design: Patient-matched MPNSTs and precursor lesions were examined by FISH, RNA sequencing, IHC, and Connectivity-Map analyses. Antitumor activity of CDK4/6 and MEK inhibitors was measured in MPNST cell lines, patient-derived xenografts (PDX), and de novo mouse MPNSTs, with the latter used to determine anti-PD-L1 response. Results: Patient tumor analyses identified CDK4/6 and MEK as actionable targets for MPNST therapy. Low-dose combinations of CDK4/6 and MEK inhibitors synergistically reactivated the retinoblastoma (RB1) tumor suppressor, induced cell death, and decreased clonogenic survival of MPNST cells. In immune-deficient mice, dual CDK4/6-MEK inhibition slowed tumor growth in 4 of 5 MPNST PDXs. In immunocompetent mice, combination therapy of de novo MPNSTs caused tumor regression, delayed resistant tumor outgrowth, and improved survival relative to monotherapies. Drug-sensitive tumors that regressed contained plasma cells and increased cytotoxic T cells, whereas drug-resistant tumors adopted an immunosuppressive microenvironment with elevated MHC II-low macrophages and increased tumor cell PD-L1 expression. Excitingly, CDK4/6-MEK inhibition sensitized MPNSTs to anti-PD-L1 immune checkpoint blockade (ICB) with some mice showing complete tumor regression. Conclusions: CDK4/6-MEK inhibition induces a novel plasma cell-associated immune response and extended antitumor activity in MPNSTs, which dramatically enhances anti-PD-L1 therapy. These preclinical findings provide strong rationale for clinical translation of CDK4/6-MEK-ICB targeted therapies in MPNST as they may yield sustained antitumor responses and improved patient outcomes.
MeSH term(s)	Mice ; Humans ; Animals ; Neurofibrosarcoma/drug therapy ; Plasma Cells/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Mitogen-Activated Protein Kinase Kinases ; Cell Line, Tumor ; Tumor Microenvironment ; Cyclin-Dependent Kinase 4
Chemical Substances	CD274 protein, human ; Protein Kinase Inhibitors ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; CDK4 protein, human (EC 2.7.11.22) ; Cyclin-Dependent Kinase 4 (EC 2.7.11.22)
Language	English
Publishing date	2023-08-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-23-0749
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Article: Nasopharyngeal carcinoma presenting as an inconspicuous primary lesion with extensive cavernous sinus involvement and temporal lobe extension: a case report and review of literature.

Pollard, Courtney / Mesko, Shane M / Ginsberg, Lawrence E / Kies, Merrill S / Raza, Shaan M / Su, Shirley Y / Tung, Sam / Phan, Jack

Clinical case reports

2017 Volume 5, Issue 10, Page(s) 1682–1688

Abstract: Detection of nodal metastasis in the neck or adjacent structures is common in nasopharyngeal carcinoma (NPC) when there is frank primary disease. Intracranial extension without obvious nasopharyngeal disease is not common. Here, we discuss a patient with ...

Abstract	Detection of nodal metastasis in the neck or adjacent structures is common in nasopharyngeal carcinoma (NPC) when there is frank primary disease. Intracranial extension without obvious nasopharyngeal disease is not common. Here, we discuss a patient with NPC that presented with extensive intracranial disease with subtle findings in the nasopharynx.
Language	English
Publishing date	2017-09-05
Publishing country	England
Document type	Case Reports
ZDB-ID	2740234-4
ISSN	2050-0904
ISSN	2050-0904
DOI	10.1002/ccr3.1166
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Article: Development of Inflammatory Bowel Disease Is Linked to a Longitudinal Restructuring of the Gut Metagenome in Mice.

Sharpton, Thomas / Lyalina, Svetlana / Luong, Julie / Pham, Joey / Deal, Emily M / Armour, Courtney / Gaulke, Christopher / Sanjabi, Shomyseh / Pollard, Katherine S

mSystems

2017 Volume 2, Issue 5

Abstract: The gut microbiome is linked to inflammatory bowel disease (IBD) severity and altered in late-stage disease. However, it is unclear how gut microbial communities change over the course of IBD development, especially in regard to function. To investigate ... ...

Abstract	The gut microbiome is linked to inflammatory bowel disease (IBD) severity and altered in late-stage disease. However, it is unclear how gut microbial communities change over the course of IBD development, especially in regard to function. To investigate microbiome-mediated disease mechanisms and discover early biomarkers of IBD, we conducted a longitudinal metagenomic investigation in an established mouse model of IBD, where damped transforming growth factor β (TGF-β) signaling in T cells leads to peripheral immune activation, weight loss, and severe colitis. IBD development is associated with abnormal gut microbiome temporal dynamics, including damped acquisition of functional diversity and significant differences in abundance trajectories for KEGG modules such as glycosaminoglycan degradation, cellular chemotaxis, and type III and IV secretion systems. Most differences between sick and control mice emerge when mice begin to lose weight and heightened T cell activation is detected in peripheral blood. However, levels of lipooligosaccharide transporter abundance diverge prior to immune activation, indicating that it could be a predisease indicator or microbiome-mediated disease mechanism. Taxonomic structure of the gut microbiome also significantly changes in association with IBD development, and the abundances of particular taxa, including several species of
Language	English
Publishing date	2017-09-05
Publishing country	United States
Document type	Journal Article
ISSN	2379-5077
ISSN	2379-5077
DOI	10.1128/mSystems.00036-17
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Article: Dosimetric advantages of stereotactic radiosurgery as a boost to adjuvant conventional radiotherapy in the setting of adenoid cystic carcinoma of the parotid with skull base invasion.

Phan, Jae L / Pollard, Courtney / Wang, He / Ng, Sweet Ping / Sheu, Tommy / Ginsberg, Lawrence E / Hessel, Amy C / Gidley, Paul W / Rosenthal, David I / Phan, Jack

Clinical case reports

2018 Volume 6, Issue 11, Page(s) 2126–2130

Abstract: This study highlights gamma knife stereotactic radiosurgery (GK-SRS) as boost therapy in a patient with adenoid cystic carcinoma of the parotid involving the skull base and invasion of the facial nerve. Using GK-SRS, dose to the brainstem and temporal ... ...

Abstract	This study highlights gamma knife stereotactic radiosurgery (GK-SRS) as boost therapy in a patient with adenoid cystic carcinoma of the parotid involving the skull base and invasion of the facial nerve. Using GK-SRS, dose to the brainstem and temporal lobe were reduced when compared to less conformal radiotherapy techniques.
Language	English
Publishing date	2018-09-23
Publishing country	England
Document type	Case Reports
ZDB-ID	2740234-4
ISSN	2050-0904
ISSN	2050-0904
DOI	10.1002/ccr3.1788
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Article ; Online: Molecular genesis of non-muscle-invasive urothelial carcinoma (NMIUC).

Pollard, Courtney / Smith, Steven C / Theodorescu, Dan

Expert reviews in molecular medicine

2010 Volume 12, Page(s) e10

Abstract: Urothelial carcinoma (UC) is the most common type of bladder cancer in Western nations. Most patients present with the non-muscle-invasive (NMIUC) form of the disease, while up to a third harbour the invasive form (MIUC). Specifically, the aetiology of ... ...

Abstract	Urothelial carcinoma (UC) is the most common type of bladder cancer in Western nations. Most patients present with the non-muscle-invasive (NMIUC) form of the disease, while up to a third harbour the invasive form (MIUC). Specifically, the aetiology of NMIUC appears to be multifactorial and very different from that of MIUC. Loss of specific tumour suppressor genes as well as gain-of-function mutations in proteins within defined cellular signalling pathways have been implicated in NMIUC aetiology. The regions of chromosome 9 that harbour CDKN2A, CDKN2B, TSC1, PTCH1 and DBC1 are frequently mutated in NMIUC, resulting in functional loss; in addition, HRAS and FGFR3, which are both proto-oncogenes encoding components of the Ras-MAPK signalling pathway, have been found to harbour activating mutations in a large number of NMIUCs. Interestingly, some of these molecular events are mutually exclusive, suggesting functional equivalence. Since several of these driving changes are amenable to therapeutic targeting, understanding the signalling events in NMIUC may offer novel approaches to manage the recurrence and progression of this disease.
MeSH term(s)	Carcinoma, Transitional Cell/genetics ; Carcinoma, Transitional Cell/pathology ; Chromosomes, Human, Pair 9/genetics ; Humans ; Muscles ; Neoplasm Invasiveness ; Proto-Oncogene Proteins p21(ras)/metabolism ; Receptor, Fibroblast Growth Factor, Type 3/metabolism ; Urothelium/pathology
Chemical Substances	Receptor, Fibroblast Growth Factor, Type 3 (EC 2.7.10.1) ; HRAS protein, human (EC 3.6.5.2) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
Language	English
Publishing date	2010-03-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ISSN	1462-3994
ISSN (online)	1462-3994
DOI	10.1017/S1462399410001407
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Article ; Online: Lymphopenia during radiotherapy in patients with oropharyngeal cancer.

Ng, Sweet Ping / Bahig, Houda / Jethanandani, Amit / Pollard, Courtney / Berends, Joel / Sturgis, Erich M / Johnson, Faye M / Elgohari, Baher / Elhalawani, Hesham / Rosenthal, David I / Skinner, Heath D / Gunn, G Brandon / Phan, Jack / Frank, Steven J / Mohamed, Abdallah S R / Fuller, Clifton D / Garden, Adam S

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

2020 Volume 145, Page(s) 95–100

Abstract: Purpose/objective: Radiation-induced lymphopenia has been associated with poor survival outcomes in certain solid tumors such as esophageal, lung, cervical and pancreatic cancers. We aim to determine the effect of treatment-related lymphopenia during ... ...

Abstract	Purpose/objective: Radiation-induced lymphopenia has been associated with poor survival outcomes in certain solid tumors such as esophageal, lung, cervical and pancreatic cancers. We aim to determine the effect of treatment-related lymphopenia during radiotherapy on outcomes of patients with oropharyngeal cancer. Materials/methods: A retrospective analysis of all patients who completed definitive radiotherapy for oropharyngeal cancer at The University of Texas MD Anderson Cancer Center and had blood counts taken during radiotherapy from 2002 to 2013 were included. Patient, tumor and treatment characteristics, clinical outcomes and lymphocyte counts during radiotherapy were recorded. Lymphopenia was graded according to the CTCAE v4.0. Survival rates were estimated using the Kaplan-Meier method and compared with log-rank tests. Results: 850 patients were evaluated. The median age was 57 years. The majority of the cohort had p16/HPV-positive disease (71%), 8% had HPV-negative disease and 21% were unknown. The median radiation total dose was 70 Gy. 45% of patients had induction chemotherapy, and 87% had concurrent chemotherapy. 703 (83%) patients developed ≥grade 3 (G3) lymphopenia and 209 (25%) had grade 4 (G4) lymphopenia during radiotherapy. The median follow-up was 59 months; the 5-year overall survival rate was 81%. There were no significant differences in overall survival rates nor in disease control rates, in those who developed G3/G4 lymphopenia compared with those who did not. No significant effect of lymphopenia on survival was observed when analyzed according to p16/HPV status. Conclusion: In this large cohort of patients with oropharyngeal cancer, the development of lymphopenia during radiotherapy did not impact outcomes.
MeSH term(s)	Humans ; Lymphocytes ; Lymphopenia/etiology ; Middle Aged ; Oropharyngeal Neoplasms/radiotherapy ; Retrospective Studies ; Survival Rate
Language	English
Publishing date	2020-01-10
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	605646-5
ISSN	1879-0887 ; 0167-8140
ISSN (online)	1879-0887
ISSN	0167-8140
DOI	10.1016/j.radonc.2019.12.023
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Zs.A 1926: Show issues

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