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Article ; Online: Immunomodulatory effects of vitamin D: implications for GVHD.

Rosenblatt, J / Bissonnette, A / Ahmad, R / Wu, Z / Vasir, B / Stevenson, K / Zarwan, C / Keefe, W / Glotzbecker, B / Mills, H / Joyce, R / Levine, J D / Tzachanis, D / Boussiotis, V / Kufe, D / Avigan, D

Bone marrow transplantation

2010 Volume 45, Issue 9, Page(s) 1463–1468

Abstract: ... allogeneic transplantation may decrease the risk of developing GVHD. Vitamin D is a hormone essential for calcium metabolism ... that shows immunomodulatory properties. We showed that correction of vitamin D deficiency appeared ... to mitigate manifestations of GVHD. In pre-clinical studies, we have shown that vitamin D inhibits DC ...

Abstract	GVHD remains a major source of morbidity and mortality after allogeneic BMT. GVHD is mediated by alloreactive T cells derived from the hematopoietic graft that target host tissues. Pre-clinical models have shown that presentation of alloantigens by host DCs results in the activation of donor-derived T cells that mediate GVHD. Strategies that interfere with the Ag-presenting capacity of DCs after allogeneic transplantation may decrease the risk of developing GVHD. Vitamin D is a hormone essential for calcium metabolism that shows immunomodulatory properties. We showed that correction of vitamin D deficiency appeared to mitigate manifestations of GVHD. In pre-clinical studies, we have shown that vitamin D inhibits DC maturation, polarizes T-cell populations toward the expression of Th2 as compared with Th1 cytokines, and blunts allogeneic T-cell proliferation in response to DC stimulation. Exposure to vitamin D resulted in increased expression of IDO, an enzyme responsible for tryptophan metabolism that is upregulated in tolerizing DCs. These data suggest that exposure to vitamin D results in immature DC populations that bias toward tolerizing rather than stimulatory T-cell populations. Vitamin D may therefore have a role in the prevention of GVHD.
MeSH term(s)	Cell Polarity/drug effects ; Cell Polarity/immunology ; Cells, Cultured ; Dendritic Cells/cytology ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Graft vs Host Disease/drug therapy ; Graft vs Host Disease/immunology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Immunologic Factors/pharmacology ; Immunophenotyping ; Mitogens/pharmacology ; Signal Transduction/drug effects ; Signal Transduction/immunology ; T-Lymphocytes/cytology ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; Vitamin D/pharmacology
Chemical Substances	Immunologic Factors ; Mitogens ; Vitamin D (1406-16-2)
Language	English
Publishing date	2010-01-18
Publishing country	England
Document type	Journal Article
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/bmt.2009.366
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Zs.A 2168: Show issues

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Article ; Online: Low levels of 25-hydroxyvitamin D before allogeneic hematopoietic SCT correlate with the development of chronic GVHD.

Glotzbecker, B / Ho, V T / Aldridge, J / Kim, H T / Horowitz, G / Ritz, J / Soiffer, R / Avigan, D / Rosenblatt, J

Bone marrow transplantation

2013 Volume 48, Issue 4, Page(s) 593–597

Abstract: Vitamin D, a hormone involved in bone and calcium homeostasis, has been shown to have potent ... immunomodulatory effects. We performed a retrospective cohort analysis to evaluate whether monohydroxyvitamin D ... who underwent myeloablative HSCT were studied. Vitamin D levels were measured in serum samples obtained ...

Abstract	Vitamin D, a hormone involved in bone and calcium homeostasis, has been shown to have potent immunomodulatory effects. We performed a retrospective cohort analysis to evaluate whether monohydroxyvitamin D levels before allogeneic hematopoietic SCT (HSCT) correlate with the risk of GVHD. Fifty-three patients who underwent myeloablative HSCT were studied. Vitamin D levels were measured in serum samples obtained before HSCT. The median 25-hydroxyvitamin vitamin D level was 21.9 ng/mL (7.8-45.7). The cumulative incidence (CI) of grades II-IV acute GVHD at 100 days was 53.1% in patients with vitamin D<25, versus 33.3% in patients with vitamin D ≥ 25 ng/mL (P=0.13). The CI of chronic GVHD (cGVHD) at 2 years in patients with vitamin D<25 was 63.8%, compared with 23.8% in patients with vitamin D ≥ 25 ng/mL (P=0.009). Similarly, the 2 year CI of extensive cGVHD was significantly greater in patients with vitamin D<25 compared with those with vitamin D ≥ 25 ng/mL (54.5% versus 14.3%, P=0.005). In a multivariable competing risk model, low pre-transplant vitamin D levels remained a significant factor associated with cGVHD (hazard ratio=5.26, P=0.02). Our results demonstrate that vitamin D deficiency before HSCT is associated with an increased risk of cGVHD.
MeSH term(s)	Acute Disease ; Adolescent ; Adult ; Chronic Disease ; Female ; Graft vs Host Disease/blood ; Graft vs Host Disease/epidemiology ; Graft vs Host Disease/etiology ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Stem Cell Transplantation ; Time Factors ; Transplantation, Homologous ; Vitamin D/analogs & derivatives ; Vitamin D/blood
Chemical Substances	Vitamin D (1406-16-2) ; 25-hydroxyvitamin D (A288AR3C9H)
Language	English
Publishing date	2013-04
Publishing country	England
Document type	Clinical Trial ; Comparative Study ; Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/bmt.2012.177
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Zs.A 2168: Show issues

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Article ; Online: Vaccination as Immunotherapy in Hematologic Malignancies.

Liegel, Jessica / Weinstock, Matthew / Rosenblatt, Jacalyn / Avigan, David

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2021 Volume 39, Issue 5, Page(s) 433–443

MeSH term(s)	Cancer Vaccines/therapeutic use ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic ; Hematologic Neoplasms/immunology ; Hematologic Neoplasms/therapy ; Humans ; Randomized Controlled Trials as Topic ; Vaccination/methods
Chemical Substances	Cancer Vaccines
Language	English
Publishing date	2021-01-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.20.01706
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 650: Show issues

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Article ; Online: Cellular Immunotherapy for Multiple Myeloma.

Rosenblatt, Jacalyn / Avigan, David

Cancer journal (Sudbury, Mass.)

2019 Volume 25, Issue 1, Page(s) 38–44

Abstract: Cellular immunotherapy for myeloma has the unique potential both to potently kill the malignant clone and to evoke a memory response to protect from relapse. Understanding the complex interactions between the malignant clone and the microenvironment that ...

Abstract	Cellular immunotherapy for myeloma has the unique potential both to potently kill the malignant clone and to evoke a memory response to protect from relapse. Understanding the complex interactions between the malignant clone and the microenvironment that promote immune escape is critical to evoke effective antimyeloma immunity. Tremendous progress has been made in the area of cancer vaccines and adoptive T-cell therapy in recent years. Careful study of the mechanisms of response and of immune escape will be critical to developing novel combination therapies and ultimately to improve outcomes for patients with myeloma.
MeSH term(s)	Humans ; Immunotherapy/methods ; Multiple Myeloma/drug therapy
Language	English
Publishing date	2019-01-14
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2018400-1
ISSN	1540-336X ; 1528-9117 ; 1081-4442
ISSN (online)	1540-336X
ISSN	1528-9117 ; 1081-4442
DOI	10.1097/PPO.0000000000000356
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Zs.A 4470: 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)
Zs.MO 163: Show issues

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Article ; Online: Flexible spatial learning requires both the dorsal and ventral hippocampus and their functional interactions with the prefrontal cortex.

Avigan, Philip D / Cammack, Katharine / Shapiro, Matthew L

Hippocampus

2020 Volume 30, Issue 7, Page(s) 733–744

Abstract: When faced with changing contingencies, animals can use memory to flexibly guide actions, engaging both frontal and temporal lobe brain structures. Damage to the hippocampus (HPC) impairs episodic memory, and damage to the prefrontal cortex (PFC) impairs ...

Abstract	When faced with changing contingencies, animals can use memory to flexibly guide actions, engaging both frontal and temporal lobe brain structures. Damage to the hippocampus (HPC) impairs episodic memory, and damage to the prefrontal cortex (PFC) impairs cognitive flexibility, but the circuit mechanisms by which these areas support flexible memory processing remain unclear. The present study investigated these mechanisms by temporarily inactivating the medial PFC (mPFC), the dorsal HPC (dHPC), and the ventral HPC (vHPC), individually and in combination, as rats learned spatial discriminations and reversals in a plus maze. Bilateral inactivation of either the dHPC or vHPC profoundly impaired spatial learning and memory, whereas bilateral mPFC inactivation primarily impaired reversal versus discrimination learning. Inactivation of unilateral mPFC together with the contralateral dHPC or vHPC impaired spatial discrimination and reversal learning, whereas ipsilateral inactivation did not. Flexible spatial learning thus depends on both the dHPC and vHPC and their functional interactions with the mPFC.
MeSH term(s)	Animals ; Hippocampus/physiology ; Male ; Nerve Net/physiology ; Prefrontal Cortex/physiology ; Rats ; Rats, Long-Evans ; Reversal Learning/physiology ; Spatial Learning/physiology
Language	English
Publishing date	2020-02-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1074352-2
ISSN	1098-1063 ; 1050-9631
ISSN (online)	1098-1063
ISSN	1050-9631
DOI	10.1002/hipo.23198
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Zs.A 3227: Show issues

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Article ; Online: Vaccine therapy in hematologic malignancies.

Avigan, David / Rosenblatt, Jacalyn

Blood

2018 Volume 131, Issue 24, Page(s) 2640–2650

Abstract: Immune-based therapy has emerged as a paradigm shift in cancer therapy with dramatic responses observed in previously incurable disease. Cancer vaccines are being developed to disrupt tumor-associated tolerance and activate and selectively expand tumor- ... ...

Abstract	Immune-based therapy has emerged as a paradigm shift in cancer therapy with dramatic responses observed in previously incurable disease. Cancer vaccines are being developed to disrupt tumor-associated tolerance and activate and selectively expand tumor-specific lymphocytes within the native effector cell repertoire while maintaining immune-regulatory protection against autoimmunity. Although individual antigen approaches result in immune response with a suggestion of clinical effect in some settings, broader efficacy may be dependent on presentation of multiple antigens that capture clonal diversity presented in the context of functionally potent antigen-presenting cells. The use of whole cell-based strategies such as dendritic cell/tumor fusions have yielded provocative results in single-arm studies and are currently being explored in multicenter randomized trials. The posttransplant setting is a potentially promising platform for vaccination due to cytoreduction and relative depletion of inhibitory accessory cells fostering greater immune responsiveness. Integration of these efforts with other immunotherapeutic strategies and agents that target the tumor microenvironment is being studied in an effort to generate durable immunologic responses with clinically meaningful impact on disease.
MeSH term(s)	Animals ; Antigen-Presenting Cells/immunology ; Cancer Vaccines/immunology ; Cancer Vaccines/therapeutic use ; Hematologic Neoplasms/immunology ; Hematologic Neoplasms/therapy ; Humans ; Immunomodulation ; Immunotherapy, Active/methods ; Lymphocyte Activation ; T-Lymphocytes/immunology ; Tumor Microenvironment
Chemical Substances	Cancer Vaccines
Language	English
Publishing date	2018-05-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2017-11-785873
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Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 364: Show issues

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Article ; Online: Updated COVID-19 clearance time among patients with cancer in the Delta and Omicron waves.

Avigan, Zachary M / Paredes, Rodrigo / Boussi, Leora S / Lam, Barbara D / Shea, Meghan E / Weinstock, Matthew J / Peters, Mary Linton B

Cancer medicine

2023 Volume 12, Issue 16, Page(s) 16869–16875

Abstract: Background: COVID-19 infection delays therapy and in-person evaluation for oncology patients, but clinic clearance criteria are not clearly defined.: Methods: We conducted a retrospective review of oncology patients with COVID-19 at a tertiary care ... ...

Abstract	Background: COVID-19 infection delays therapy and in-person evaluation for oncology patients, but clinic clearance criteria are not clearly defined. Methods: We conducted a retrospective review of oncology patients with COVID-19 at a tertiary care center during the Delta and Omicron waves and compared clearance strategies. Results: Median clearance by two consecutive negative tests was 32.0 days (Interquartile Range [IQR] 22.0-42.5, n = 153) and was prolonged in hematologic malignancy versus solid tumors (35.0 days for hematologic malignancy, 27.5 days for solid tumors, p = 0.01) and in patients receiving B-cell depletion versus other therapies. Median clearance by single negative test was reduced to 23.0 days (IQR 16.0-33.0), with recurrent positive rate 25.4% in hematologic malignancy versus 10.6% in solid tumors (p = 0.02). Clearance by a predefined waiting period required 41 days until an 80% negative rate. Conclusions: COVID-19 clearance remains prolonged in oncology patients. Single-negative test clearance can balance delays in care with risk of infection in patients with solid tumors.
MeSH term(s)	Humans ; COVID-19 ; Neoplasms/complications ; Hematologic Neoplasms ; Medical Oncology ; B-Lymphocytes
Language	English
Publishing date	2023-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.6311
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Article ; Online: Acute Cholecystitis Associated With the Use of Glucagon-Like Peptide-1 Receptor Agonists Reported to the US Food and Drug Administration.

Woronow, Daniel / Chamberlain, Christine / Niak, Ali / Avigan, Mark / Houstoun, Monika / Kortepeter, Cindy

JAMA internal medicine

2022 Volume 182, Issue 10, Page(s) 1104–1106

MeSH term(s)	Cholecystitis, Acute ; Diabetes Mellitus, Type 2 ; Glucagon-Like Peptide 1/agonists ; Glucagon-Like Peptide-1 Receptor/agonists ; Humans ; Hypoglycemic Agents/adverse effects ; United States ; United States Food and Drug Administration
Chemical Substances	Glucagon-Like Peptide-1 Receptor ; Hypoglycemic Agents ; Glucagon-Like Peptide 1 (89750-14-1)
Language	English
Publishing date	2022-08-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2699338-7
ISSN	2168-6114 ; 2168-6106
ISSN (online)	2168-6114
ISSN	2168-6106
DOI	10.1001/jamainternmed.2022.3810
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Article ; Online: Effect of an obesogenic high-fat and high-sucrose diet on hepatic gene expression signatures in male Collaborative Cross mice.

Tryndyak, Volodymyr P / Willett, Rose A / Nagumalli, Suresh K / Li, Dan / Avigan, Mark I / Beland, Frederick A / Rusyn, Ivan / Pogribny, Igor P

American journal of physiology. Gastrointestinal and liver physiology

2023 Volume 324, Issue 3, Page(s) G232–G243

Abstract: Nonalcoholic fatty liver disease (NAFLD), the most prevalent chronic liver disease, is characterized by substantial variations in case-level severity. In this study, we used a genetically diverse Collaborative Cross (CC) mouse population model to analyze ...

Abstract	Nonalcoholic fatty liver disease (NAFLD), the most prevalent chronic liver disease, is characterized by substantial variations in case-level severity. In this study, we used a genetically diverse Collaborative Cross (CC) mouse population model to analyze the global transcriptome and clarify the molecular mechanisms involved in hepatic fat accumulation that determine the level and severity of NAFLD. Twenty-four strains of male CC mice were maintained on a high-fat/high-sucrose (HF/HS) diet for 12 wk, and their hepatic gene expression profiles were determined by next-generation RNA sequencing. We found that the development of the nonalcoholic fatty liver (NAFL) phenotype in CC mice coincided with significant changes in the expression of hepatic genes at the population level, evidenced by the presence of 724 differentially expressed genes involved in lipid and carbohydrate metabolism, cell morphology, vitamin and mineral metabolism, energy production, and DNA replication, recombination, and repair. Importantly, expression of 68 of these genes strongly correlated with the extent of hepatic lipid accumulation in the overall population of HF/HS diet-fed male CC mice. Results of partial least squares (PLS) modeling showed that these derived hepatic gene expression signatures help to identify the individual mouse strains that are highly susceptible to the development of NAFLD induced by an HF/HS diet. These findings imply that gene expression profiling, combined with a PLS modeling approach, may be a useful tool to predict NAFLD severity in genetically diverse patient populations.
MeSH term(s)	Male ; Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism ; Transcriptome ; Collaborative Cross Mice/genetics ; Sucrose/metabolism ; Liver/metabolism ; Diet, High-Fat ; Lipids ; Mice, Inbred C57BL ; Lipid Metabolism
Chemical Substances	Sucrose (57-50-1) ; Lipids
Language	English
Publishing date	2023-01-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	603840-2
ISSN	1522-1547 ; 0193-1857
ISSN (online)	1522-1547
ISSN	0193-1857
DOI	10.1152/ajpgi.00225.2022
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Article ; Online: Amiodarone and Dronedarone Causes Liver Injury with Distinctly Different Clinical Presentations.

Pop, Alexander / Halegoua-DeMarzio, Dina / Barnhart, Huiman / Kleiner, David / Avigan, Mark / Gu, Jiezhun / Chalasani, Naga / Ahmad, Jawad / Fontana, Robert J / Lee, William / Barritt, A Sidney / Durazo, Francisco / Hayashi, Paul H / Navarro, Victor J

Digestive diseases and sciences

2024 Volume 69, Issue 4, Page(s) 1479–1487

Abstract: Objective: To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database.: Methods: Hepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) ... ...

Abstract	Objective: To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database. Methods: Hepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) from 2004 to 2020 are described. Dronedarone hepatotoxicity cases associated with liver biopsy results were obtained from the FDA Adverse Event Reporting System (FAERS) from 2009 to 2020. Results: Among DILIN's 10 amiodarone and 3 dronedarone DILIN cases, the latency for amiodarone was longer than with dronedarone (388 vs 119 days, p = 0.50) and the median ALT at DILI onset was significantly lower with amiodarone (118 vs 1191 U/L, p = 0.05). Liver biopsies in five amiodarone cases showed fibrosis, steatosis, and numerous Mallory-Denk bodies. Five patients died although only one from liver failure. One patient with dronedarone induced liver injury died of a non-liver related cause. Nine additional cases of DILI due to dronedarone requiring hospitalization were identified in the FAERS database. Three patients developed liver injury within a month of starting the medication. Two developed acute liver failure and underwent urgent liver transplant, one was evaluated for liver transplant but then recovered spontaneously, while one patient with cirrhosis died of liver related causes. Conclusion: Amiodarone hepatotoxicity resembles that seen in alcohol related liver injury, with fatty infiltration and inflammation. Dronedarone is less predictable, typically without fat and with a shorter latency of use before presentation. These differences may be explained, in part, by the differing pharmacokinetics of the two drugs leading to different mechanisms of hepatotoxicity.
MeSH term(s)	Humans ; Dronedarone ; Amiodarone/adverse effects ; Amiodarone/pharmacokinetics ; Anti-Arrhythmia Agents/adverse effects ; Anti-Arrhythmia Agents/pharmacokinetics ; Dyphylline ; Chemical and Drug Induced Liver Injury
Chemical Substances	Dronedarone (JQZ1L091Y2) ; Amiodarone (N3RQ532IUT) ; Anti-Arrhythmia Agents ; Dyphylline (263T0E9RR9)
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	304250-9
ISSN	1573-2568 ; 0163-2116
ISSN (online)	1573-2568
ISSN	0163-2116
DOI	10.1007/s10620-023-08251-2
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