LIVIVO - Search results -

Search results

Result 1 - 10 of total 17

Search options

Article ; Online: Association between Controlling Nutritional Status (CONUT) Score and Body Composition, Inflammation and Frailty in Hospitalized Elderly Patients.

Lo Buglio, Aurelio / Bellanti, Francesco / Carmignano, Daniela Francesca Pia / Serviddio, Gaetano / Vendemiale, Gianluigi

Nutrients

2024 Volume 16, Issue 5

Abstract: The Controlling Nutritional Status (CONUT) score has demonstrated its ability to identify patients with poor nutritional status and predict various clinical outcomes. Our objective was to assess the association between the CONUT score, inflammatory ... ...

Abstract	The Controlling Nutritional Status (CONUT) score has demonstrated its ability to identify patients with poor nutritional status and predict various clinical outcomes. Our objective was to assess the association between the CONUT score, inflammatory status, and body composition, as well as its ability to identify patients at risk of frailty in hospitalized elderly patients. Methods: a total of 361 patients were retrospectively recruited and divided into three groups based on the CONUT score. Results: patients with a score ≥5 exhibited significantly higher levels of inflammatory markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Neutrophil/Lymphocytes ratio (NLR), main platelet volume (MPV), and ferritin, compared to those with a lower score. Furthermore, these patients showed unfavorable changes in body composition, including a lower percentage of skeletal muscle mass (MM) and fat-free mass (FFM) and a higher percentage of fatty mass (FM). A positive correlation was found between the CONUT score and inflammatory markers, Geriatric Depression Scale Short Form (GDS-SF), and FM. Conversely, the Mini Nutritional Assessment (MNA), Mini-Mental Status Examination, activity daily living (ADL), instrumental activity daily living (IADL), Barthel index, FFM, and MM showed a negative correlation. Frailty was highly prevalent among patients with a higher CONUT score. The receiver operating characteristic (ROC) curve demonstrated high accuracy in identifying frail patients (sensitivity). Conclusions: a high CONUT score is associated with a pro-inflammatory status as well as with unfavorable body composition. Additionally, it is a good tool to identify frailty among hospitalized elderly patients.
MeSH term(s)	Humans ; Aged ; Nutritional Status ; Frailty/complications ; Retrospective Studies ; Nutrition Assessment ; Malnutrition/diagnosis ; Inflammation/complications ; Prognosis
Language	English
Publishing date	2024-02-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu16050576
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Histone deacetylase inhibitors in Hodgkin lymphoma.

Buglio, Daniela / Younes, Anas

Investigational new drugs

2010 Volume 28 Suppl 1, Page(s) S21–7

Abstract: Although Hodgkin lymphoma (HL) is considered one of the most curable human cancers, the treatment of patients with relapsed and refractory disease, especially those who relapse after autologous stem cell transplantation, remains challenging. Furthermore, ...

Abstract	Although Hodgkin lymphoma (HL) is considered one of the most curable human cancers, the treatment of patients with relapsed and refractory disease, especially those who relapse after autologous stem cell transplantation, remains challenging. Furthermore, because of the young age of these patients, the impact of early mortality on the number of years lost from productive life is remarkable. Patients with relapsed HL post stem cell transplantation currently have no curative therapy, and are in need for new drugs and novel treatment strategies. While no new drugs have been approved for the treatment of patients with HL in more than three decades, several new agents are demonstrating promising results in early clinical trials. This review will focus on the emerging role of histone deacetylase inhibitors in patients with relapsed HL.
MeSH term(s)	Clinical Trials as Topic ; Epigenesis, Genetic/drug effects ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylase Inhibitors/therapeutic use ; Histone Deacetylases/metabolism ; Hodgkin Disease/drug therapy ; Hodgkin Disease/enzymology ; Humans ; Recurrence
Chemical Substances	Histone Deacetylase Inhibitors ; Histone Deacetylases (EC 3.5.1.98)
Language	English
Publishing date	2010-12-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	604895-x
ISSN	1573-0646 ; 0167-6997
ISSN (online)	1573-0646
ISSN	0167-6997
DOI	10.1007/s10637-010-9588-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1823: 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)

Order via subito

Details ▾

Article ; Online: Histone deacetylase inhibitors in lymphoma.

Copeland, Amanda / Buglio, Daniela / Younes, Anas

Current opinion in oncology

2010 Volume 22, Issue 5, Page(s) 431–436

Abstract: Purpose of review: Although many advances have been made in the treatment of lymphoma in the past decade, the treatment of patients with relapsed and refractory disease remains challenging. Only a fraction of patients will be cured with salvage therapy ... ...

Abstract	Purpose of review: Although many advances have been made in the treatment of lymphoma in the past decade, the treatment of patients with relapsed and refractory disease remains challenging. Only a fraction of patients will be cured with salvage therapy and transplantation. For those patients that are either ineligible or relapse after transplant, the treatment options are limited. This illustrates the need for new drugs and novel treatment strategies. This review will focus on the emerging role of histone deacetylase inhibitors (HDACis) in patients with relapsed lymphoma. Recent findings: Several HDACis have been evaluated in relapsed and refractory Hodgkin and non-Hodgkin lymphoma showing promising activity in both. Specifically, vorinostat and romidepsin have been approved by the US Food and Drug Administration for patients with relapsed or refractory cutaneous T-cell lymphoma. Several other HDACis have shown very promising activity in Hodgkin lymphoma including panobinostat, entinostat and mocetinostat. Summary: With the limited options available for lymphoma patients in the relapsed and refractory setting, the efficacy demonstrated by HDACis in this patient population is exciting and much needed and will hopefully prompt further investigation into additional agents and into the combination with HDACis.
MeSH term(s)	Clinical Trials as Topic ; Histone Deacetylase Inhibitors/therapeutic use ; Humans ; Lymphoma/drug therapy ; Prognosis
Chemical Substances	Histone Deacetylase Inhibitors
Language	English
Publishing date	2010-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1049384-0
ISSN	1531-703X ; 1040-8746
ISSN (online)	1531-703X
ISSN	1040-8746
DOI	10.1097/CCO.0b013e32833d5954
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3046: 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)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Novel small-molecule therapy of Hodgkin lymphoma.

Buglio, Daniela / Georgakis, Georgios / Younes, Anas

Expert review of anticancer therapy

2007 Volume 7, Issue 5, Page(s) 735–740

Abstract: The treatment of Hodgkin lymphoma continues to be based on combination chemotherapy and radiation therapy. Although this treatment strategy produces a high cure rate, short- and long-term toxic effects continue to be problematic for young cured patients. ...

Abstract	The treatment of Hodgkin lymphoma continues to be based on combination chemotherapy and radiation therapy. Although this treatment strategy produces a high cure rate, short- and long-term toxic effects continue to be problematic for young cured patients. In this review we focus on emerging novel therapies using small molecules that target specific survival pathways in the cancer cells. This approach is aimed at improving the cure rate while reducing treatment-related toxicity.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; HSP90 Heat-Shock Proteins/antagonists & inhibitors ; Histone Deacetylase Inhibitors ; Hodgkin Disease/drug therapy ; Humans ; Mitogen-Activated Protein Kinases/antagonists & inhibitors ; Phosphatidylinositol 3-Kinases/antagonists & inhibitors ; Proteasome Inhibitors ; Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors ; Signal Transduction/drug effects
Chemical Substances	Antineoplastic Agents ; HSP90 Heat-Shock Proteins ; Histone Deacetylase Inhibitors ; Proteasome Inhibitors ; Proto-Oncogene Proteins c-bcl-2 ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2007-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2112544-2
ISSN	1744-8328 ; 1473-7140
ISSN (online)	1744-8328
ISSN	1473-7140
DOI	10.1586/14737140.7.5.735
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5907: 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)

Order via subito

Details ▾

Article ; Online: ENGAGE- 501: phase II study of entinostat (SNDX-275) in relapsed and refractory Hodgkin lymphoma.

Batlevi, Connie Lee / Kasamon, Yvette / Bociek, R Gregory / Lee, Peter / Gore, Lia / Copeland, Amanda / Sorensen, Rachel / Ordentlich, Peter / Cruickshank, Scott / Kunkel, Lori / Buglio, Daniela / Hernandez-Ilizaliturri, Francisco / Younes, Anas

Haematologica

2016 Volume 101, Issue 8, Page(s) 968–975

Abstract: Classical Hodgkin lymphoma treatment is evolving rapidly with high response rates from antibody-drug conjugates targeting CD30 and immune checkpoint antibodies. However, most patients do not achieve a complete response, therefore development of novel ... ...

Abstract	Classical Hodgkin lymphoma treatment is evolving rapidly with high response rates from antibody-drug conjugates targeting CD30 and immune checkpoint antibodies. However, most patients do not achieve a complete response, therefore development of novel therapies is warranted to improve patient outcomes. In this phase II study, patients with relapsed or refractory Hodgkin lymphoma were treated with entinostat, an isoform selective histone deacetylase inhibitor. Forty-nine patients were enrolled: 33 patients on Schedule A (10 or 15 mg oral entinostat once every other week); 16 patients on Schedule B (15 mg oral entinostat once weekly in 3 of 4 weeks). Patients received a median of 3 prior treatments (range 1-10), with 80% of the patients receiving a prior stem cell transplant and 8% of patients receiving prior brentuximab vedotin. In the intention-to-treat analysis, the overall response rate was 12% while the disease control rate (complete response, partial response, and stable disease beyond 6 months) was 24%. Seven patients did not complete the first cycle due to progression of disease. Tumor reduction was observed in 24 of 38 (58%) evaluable patients. Median progression-free survival and overall survival was 5.5 and 25.1 months, respectively. The most frequent grade 3 or 4 adverse events were thrombocytopenia (63%), anemia (47%), neutropenia (41%), leukopenia (10%), hypokalemia (8%), and hypophosphatemia (6%). Twenty-five (51%) patients required dose reductions or delays. Pericarditis/pericardial effusion occurred in one patient after 12 cycles of therapy. Future studies are warranted to identify predictive biomarkers for treatment response and to develop mechanism-based combination strategies. (clinicaltrials.gov identifier: 00866333).
MeSH term(s)	Adult ; Aged ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/therapeutic use ; Benzamides/administration & dosage ; Benzamides/adverse effects ; Benzamides/pharmacokinetics ; Benzamides/therapeutic use ; Combined Modality Therapy ; Cytokines/blood ; Drug Resistance, Neoplasm ; Female ; Follow-Up Studies ; Histone Deacetylase Inhibitors/administration & dosage ; Histone Deacetylase Inhibitors/adverse effects ; Histone Deacetylase Inhibitors/pharmacokinetics ; Histone Deacetylase Inhibitors/therapeutic use ; Hodgkin Disease/diagnosis ; Hodgkin Disease/drug therapy ; Hodgkin Disease/mortality ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multimodal Imaging ; Pyridines/administration & dosage ; Pyridines/adverse effects ; Pyridines/pharmacokinetics ; Pyridines/therapeutic use ; Recurrence ; Retreatment ; Treatment Outcome ; Young Adult
Chemical Substances	Antineoplastic Agents ; Benzamides ; Cytokines ; Histone Deacetylase Inhibitors ; Pyridines ; entinostat (1ZNY4FKK9H)
Language	English
Publishing date	2016-08
Publishing country	Italy
Document type	Clinical Trial, Phase II ; Journal Article ; Multicenter Study
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2016.142406
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

In stock of ZB MED Cologne/Königswinter

Uh III Zs.76: 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)

Order via subito

Details ▾

Article ; Online: Essential role of TAK1 in regulating mantle cell lymphoma survival.

Buglio, Daniela / Palakurthi, Sangeetha / Byth, Kate / Vega, Francisco / Toader, Dorin / Saeh, Jamal / Neelapu, Sattva S / Younes, Anas

Blood

2012 Volume 120, Issue 2, Page(s) 347–355

Abstract: TGF-β-activated kinase 1 (TAK1), a member of the MAPK kinase family, plays a key role in B-cell growth and development. In the present study, we examined the potential role of TAK1 as a therapeutic target for lymphoma. Here, we show that the active ... ...

Abstract	TGF-β-activated kinase 1 (TAK1), a member of the MAPK kinase family, plays a key role in B-cell growth and development. In the present study, we examined the potential role of TAK1 as a therapeutic target for lymphoma. Here, we show that the active phosphorylated form of TAK1 is abundantly expressed in a panel of lymphoma cell lines, including mantle cell, anaplastic large cell, and Hodgkin lymphoma cell lines. Silencing TAK1 expression via the use of siRNA inhibited the activation of NF-κB and p38 and induced apoptosis in lymphoma cell lines. Moreover, submicromolar concentrations of AZ-TAK1, a novel ATP-competitive small molecule inhibitor of TAK1, dephosphorylated TAK1, p38, and IκB-α in lymphoma cell lines. These molecular events were associated with the release of cytochrome c into the cytosol, down-regulation of X-linked inhibitor of apoptosis, activation of caspase 9, and induction of apoptosis. We also demonstrate that primary lymphoma cells express TAK1 and pTAK1 and were sensitive to AZ-TAK1-mediated cell death. Collectively, our data demonstrate an essential role for TAK1 in regulating critical survival mechanisms in lymphoma and suggest that it may serve as a therapeutic target.
MeSH term(s)	Apoptosis ; Cell Line, Tumor ; Cell Survival/genetics ; Cell Survival/physiology ; Hodgkin Disease/enzymology ; Hodgkin Disease/genetics ; Hodgkin Disease/pathology ; Humans ; I-kappa B Proteins/metabolism ; Lymphoma, Large-Cell, Anaplastic/enzymology ; Lymphoma, Large-Cell, Anaplastic/genetics ; Lymphoma, Large-Cell, Anaplastic/pathology ; Lymphoma, Mantle-Cell/drug therapy ; Lymphoma, Mantle-Cell/enzymology ; Lymphoma, Mantle-Cell/genetics ; Lymphoma, Mantle-Cell/pathology ; MAP Kinase Kinase Kinases/antagonists & inhibitors ; MAP Kinase Kinase Kinases/chemistry ; MAP Kinase Kinase Kinases/genetics ; MAP Kinase Kinase Kinases/physiology ; Models, Molecular ; NF-KappaB Inhibitor alpha ; NF-kappa B/metabolism ; Phosphorylation ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacology ; RNA, Small Interfering/genetics ; p38 Mitogen-Activated Protein Kinases/metabolism
Chemical Substances	I-kappa B Proteins ; NF-kappa B ; NFKBIA protein, human ; Protein Kinase Inhibitors ; RNA, Small Interfering ; NF-KappaB Inhibitor alpha (139874-52-5) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; MAP Kinase Kinase Kinases (EC 2.7.11.25) ; MAP kinase kinase kinase 7 (EC 2.7.11.25)
Language	English
Publishing date	2012-05-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2011-07-369397
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

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

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The pan-deacetylase inhibitor panobinostat induces cell death and synergizes with everolimus in Hodgkin lymphoma cell lines.

Lemoine, Manuela / Derenzini, Enrico / Buglio, Daniela / Medeiros, L Jeffrey / Davis, R Eric / Zhang, Jiexin / Ji, Yuan / Younes, Anas

Blood

2012 Volume 119, Issue 17, Page(s) 4017–4025

Abstract: The pan-deacetylase inhibitor panobinostat (LBH589) recently has been shown to have significant clinical activity in patients with relapsed Hodgkin lymphoma, but its mechanism of action in Hodgkin lymphoma remains unknown. In this study, we demonstrate ... ...

Abstract	The pan-deacetylase inhibitor panobinostat (LBH589) recently has been shown to have significant clinical activity in patients with relapsed Hodgkin lymphoma, but its mechanism of action in Hodgkin lymphoma remains unknown. In this study, we demonstrate that panobinostat has potent antiproliferative activity against Hodgkin lymphoma-derived cell lines. At the molecular level, panobinostat activated the caspase pathway, inhibited STAT5 and STAT6 phosphorylation, and down-regulated hypoxia-inducible factor 1 α and its downstream targets, glucose transporter 1 (GLUT1) and vascular endothelial growth factor. Paradoxically, panobinostat inhibited LKB1 and AMP-activated protein kinase, leading to activation of mammalian target of rapamycin (mTOR) that promotes survival. Combining panobinostat with the mTOR inhibitor everolimus (RAD001) inhibited panobinostat-induced mTOR activation and enhanced panobinostat antiproliferative effects. Collectively, our data demonstrate that panobinostat is a potent deacetylase inhibitor against Hodgkin lymphoma-derived cell lines, and provide a mechanistic rationale for combining panobinostat with mTOR inhibitors for treating Hodgkin lymphoma patients. Furthermore, the effect of panobinostat on GLUT1 expression suggests that panobinostat may modulate the results of clinical diagnostic imaging tests that depend of functional GLUT1, such as fluorodeoxyglucose positron emission tomography.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Apoptosis/drug effects ; Blotting, Western ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Chemokines/metabolism ; Cytokines/metabolism ; Drug Synergism ; Everolimus ; Flow Cytometry ; Glucose Transporter Type 1/metabolism ; Histone Deacetylase Inhibitors/pharmacology ; Hodgkin Disease/drug therapy ; Hodgkin Disease/metabolism ; Hodgkin Disease/pathology ; Humans ; Hydroxamic Acids/pharmacology ; Hypoxia-Inducible Factor 1/metabolism ; Immunosuppressive Agents/pharmacology ; Indoles ; Panobinostat ; Phosphorylation/drug effects ; Protein-Serine-Threonine Kinases/metabolism ; STAT5 Transcription Factor/metabolism ; STAT6 Transcription Factor/metabolism ; Sirolimus/analogs & derivatives ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases/metabolism ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Chemokines ; Cytokines ; Glucose Transporter Type 1 ; Histone Deacetylase Inhibitors ; Hydroxamic Acids ; Hypoxia-Inducible Factor 1 ; Immunosuppressive Agents ; Indoles ; SLC2A1 protein, human ; STAT5 Transcription Factor ; STAT6 Transcription Factor ; STAT6 protein, human ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Panobinostat (9647FM7Y3Z) ; Everolimus (9HW64Q8G6G) ; STK11 protein, human (EC 2.7.1.-) ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2012-03-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2011-01-331421
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

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

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: HDAC11 plays an essential role in regulating OX40 ligand expression in Hodgkin lymphoma.

Buglio, Daniela / Khaskhely, Noor M / Voo, Kui Shin / Martinez-Valdez, Hector / Liu, Yong-Jun / Younes, Anas

Blood

2011 Volume 117, Issue 10, Page(s) 2910–2917

Abstract: In Hodgkin lymphoma (HL), the malignant cells are surrounded by a large number of reactive infiltrating inflammatory cells, including OX40-expressing T cells and interleukin 10 (IL-10)-producing regulatory T (T-reg) cells. These T-reg cells can suppress ... ...

Abstract	In Hodgkin lymphoma (HL), the malignant cells are surrounded by a large number of reactive infiltrating inflammatory cells, including OX40-expressing T cells and interleukin 10 (IL-10)-producing regulatory T (T-reg) cells. These T-reg cells can suppress the immune response and thus contribute to the maintenance of immune tolerance and to insufficient antitumor response. The engagement of OX40L with the OX40 receptor is essential for the generation of antigen-specific memory T cells and for the induction of host antitumor immunity. In the present study, we investigated whether histone deacetylase inhibitors (HDACis) may induce a favorable antitumor immune response by regulating the expression of OX40L in HL. We found that HDACis up-regulated OX40L surface expression in HL cell lines in a dose-dependent manner. Small interfering RNAs (siRNAs) that selectively inhibited HDAC11 expression, significantly up-regulated OX40L and induced apoptosis in HL cell lines, and silencing HDAC11 transcripts increased the production of tumor necrosis-α (TNF-α) and IL-17 in the supernatants of HL cells. Furthermore, HDACI-induced OX40L inhibited the generation of IL-10-producing type 1 T-reg cells. These results demonstrate for the first time that HDAC11 plays an essential role in regulating OX40L expression. Pharmacologic inhibition of HDAC11 may produce a favorable antitumor immune response in patients with HL.
MeSH term(s)	Blotting, Western ; Cell Line, Tumor ; Cell Separation ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Gene Expression/drug effects ; Gene Expression/genetics ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Expression Regulation, Neoplastic/genetics ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylases/drug effects ; Histone Deacetylases/genetics ; Histone Deacetylases/metabolism ; Hodgkin Disease/genetics ; Hodgkin Disease/metabolism ; Humans ; OX40 Ligand/biosynthesis ; OX40 Ligand/drug effects ; OX40 Ligand/genetics ; RNA, Small Interfering ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection
Chemical Substances	Histone Deacetylase Inhibitors ; OX40 Ligand ; RNA, Small Interfering ; HDAC11 protein, human (EC 3.5.1.98) ; Histone Deacetylases (EC 3.5.1.98)
Language	English
Publishing date	2011-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2010-08-303701
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

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

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The class-I HDAC inhibitor MGCD0103 induces apoptosis in Hodgkin lymphoma cell lines and synergizes with proteasome inhibitors by an HDAC6-independent mechanism.

Buglio, Daniela / Mamidipudi, Vidya / Khaskhely, Noor M / Brady, Helen / Heise, Carla / Besterman, Jeffrey / Martell, Robert E / MacBeth, Kyle / Younes, Anas

British journal of haematology

2010 Volume 151, Issue 4, Page(s) 387–396

Abstract: Inhibition of histone deacetylase 6 (HDAC6)-dependent aggresome function by pan HDAC inhibitors was recently reported to be a key mechanism underlying the synergistic activity between proteasome inhibitors and HDAC inhibitors in a variety of tumour types. ...

Abstract	Inhibition of histone deacetylase 6 (HDAC6)-dependent aggresome function by pan HDAC inhibitors was recently reported to be a key mechanism underlying the synergistic activity between proteasome inhibitors and HDAC inhibitors in a variety of tumour types. Because these combinations induce significant thrombocytopenia in vivo, we examined whether less toxic, isotype-selective HDAC inhibitors may still synergize with proteasome inhibitors, and if so, by what mechanisms. Here, we showed that the class I HDAC inhibitor, MGCD0103, has a potent antiproliferative activity in Hodgkin lymphoma (HL) cell lines. Furthermore, MGCD0103 induced tumour necrosis factor α (TNF-α) expression and secretion, which was associated with nuclear factor (NF)-κB activation. Selective inhibition of TNF-α expression by short interfering mRNA, or inhibition of MGCD0103-induced NF-kB activation by proteasome inhibitors enhanced MGCD0103-induced cell death. Thus, our results demonstrate that MGCD0103 may synergize with proteasome inhibitors by HDAC6-independent mechanisms, providing mechanistic rationale for exploring this potentially less toxic combination for the treatment of lymphoma.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Benzamides/pharmacology ; Boronic Acids/pharmacology ; Bortezomib ; Cytokines/biosynthesis ; Cytokines/genetics ; Drug Screening Assays, Antitumor/methods ; Drug Synergism ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic/drug effects ; Histone Deacetylase 6 ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylases/physiology ; Hodgkin Disease/pathology ; Humans ; NF-kappa B/metabolism ; Protease Inhibitors/pharmacology ; Pyrazines/pharmacology ; Pyrimidines/pharmacology ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/biosynthesis ; Tumor Necrosis Factor-alpha/genetics ; Up-Regulation/drug effects
Chemical Substances	Antineoplastic Agents ; Benzamides ; Boronic Acids ; Cytokines ; Histone Deacetylase Inhibitors ; NF-kappa B ; Protease Inhibitors ; Pyrazines ; Pyrimidines ; Tumor Necrosis Factor-alpha ; Bortezomib (69G8BD63PP) ; mocetinostat (A6GWB8T96J) ; HDAC6 protein, human (EC 3.5.1.98) ; Histone Deacetylase 6 (EC 3.5.1.98) ; Histone Deacetylases (EC 3.5.1.98)
Language	English
Publishing date	2010-09-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/j.1365-2141.2010.08342.x
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Uh III Zs.182: 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)

Order via subito

Details ▾

Article ; Online: Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study.

Younes, Anas / Brody, Joshua / Carpio, Cecilia / Lopez-Guillermo, Armando / Ben-Yehuda, Dina / Ferhanoglu, Burhan / Nagler, Arnon / Ozcan, Muhit / Avivi, Irit / Bosch, Francesc / Caballero Barrigón, Maria Dolores / Hellmann, Andrzej / Kuss, Bryone / Ma, David D F / Demirkan, Fatih / Yağci, Münci / Horowitz, Netanel A / Marlton, Paula / Cordoba, Raul /

Wrobel, Tomasz / Buglio, Daniela / Streit, Michael / Hodkinson, Brendan P / Schaffer, Michael / Alvarez, John / Ceulemans, Rob / Balasubramanian, Sriram / de Jong, Jan / Wang, Shean-Sheng / Fourneau, Nele / Jurczak, Wojciech

The Lancet. Haematology

2019 Volume 6, Issue 2, Page(s) e67–e78

Abstract: Background: Preclinical studies have shown synergistic antitumour effects between ibrutinib and immune-checkpoint blockade. The aim of this study was to assess the safety and activity of ibrutinib in combination with nivolumab in patients with relapsed ... ...

Abstract	Background: Preclinical studies have shown synergistic antitumour effects between ibrutinib and immune-checkpoint blockade. The aim of this study was to assess the safety and activity of ibrutinib in combination with nivolumab in patients with relapsed or refractory B-cell malignant diseases. Methods: We did a two-part, open-label, phase 1/2a study at 21 hospitals in Australia, Israel, Poland, Spain, Turkey, and the USA. The primary objective of part A (dose escalation) was to assess the safety of daily oral ibrutinib (420 mg or 560 mg) in combination with intravenous nivolumab (3 mg/kg every 2 weeks) to ascertain a recommended phase 2 dose in patients with relapsed or refractory high-risk chronic lymphocytic leukaemia or small lymphocytic lymphoma (del17p or del11q), follicular lymphoma, or diffuse large B-cell lymphoma. Dose optimisation was investigated using a modified toxicity probability interval design. The primary objective of the part B expansion phase was to establish the preliminary activity (the proportion of patients who achieved an overall response) of the combination of ibrutinib and nivolumab in four cohorts: relapsed or refractory high-risk chronic lymphocytic leukaemia or small lymphocytic lymphoma (del17p or del11q), follicular lymphoma, diffuse large B-cell lymphoma, and Richter's transformation. All participants who received at least one dose of treatment were included in the primary analysis and analyses were done by disease cohort. This trial is registered with ClinicalTrials.gov, number NCT02329847. The trial is ongoing. Findings: Between March 12, 2015, and April 11, 2017, 144 patients were enrolled in the study. Three patients died before receiving study treatment; thus, 141 patients were included in the analysis, 14 in part A and 127 in part B. One dose-limiting toxicity (grade 3 hyperbilirubinaemia) was reported at the 420 mg dose in the diffuse large B-cell lymphoma cohort, which resolved after 5 days. The combination of ibrutinib and nivolumab led to overall responses in 22 (61%) of 36 patients with high-risk chronic lymphocytic leukaemia or small lymphocytic lymphoma, 13 (33%) of 40 patients with follicular lymphoma, 16 (36%) of 45 patients with diffuse large B-cell lymphoma, and 13 (65%) of 20 patients with Richter's transformation. The most common all-grade adverse events were diarrhoea (47 [33%] of 141 patients), neutropenia (44 [31%]), and fatigue (37 [26%]). 11 (8%) of 141 patients had adverse events leading to death; none were reported as drug-related. The most common grade 3-4 adverse events were neutropenia (40 [28%] of 141 patients) and anaemia (32 [23%]). The incidence of grade 3-4 neutropenia ranged from eight (18%) of 45 patients with diffuse large B-cell lymphoma to 19 (53%) of 36 patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma; incidence of grade 3-4 anaemia ranged from five (13%) of 40 patients with follicular lymphoma to seven (35%) of 20 patients with Richter's transformation. The most common serious adverse events included anaemia (six [4%] of 141 patients) and pneumonia (five [4%]). The most common grade 3-4 immune-related adverse events were rash (11 [8%] of 141 patients) and increased alanine aminotransferase (three [2%]). Interpretation: The combination of ibrutinib and nivolumab had an acceptable safety profile and preliminary activity was similar to that reported with single-agent ibrutinib in chronic lymphocytic leukaemia or small lymphocytic lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma. The clinical response in patients with Richter's transformation was promising and supports further clinical assessment. Funding: Janssen R&D.
MeSH term(s)	Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Lymphoma, Non-Hodgkin/drug therapy ; Male ; Middle Aged ; Nivolumab/adverse effects ; Nivolumab/therapeutic use ; Pyrazoles/adverse effects ; Pyrazoles/therapeutic use ; Pyrimidines/adverse effects ; Pyrimidines/therapeutic use ; Recurrence ; Safety
Chemical Substances	Pyrazoles ; Pyrimidines ; ibrutinib (1X70OSD4VX) ; Nivolumab (31YO63LBSN)
Language	English
Publishing date	2019-01-11
Publishing country	England
Document type	Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article
ISSN	2352-3026
ISSN (online)	2352-3026
DOI	10.1016/S2352-3026(18)30217-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED