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Article ; Online: Potent antibacterial activity in surgical wounds with local administration of D-PLEX

Emanuel, Noam / Kozloski, Goldi A / Nedvetzki, Shlomo / Rosenfeld, Sefi

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

2023 Volume 188, Page(s) 106504

Abstract: Despite significant advances in infection control guidelines and practices, surgical site infections remain a substantial cause of morbidity, prolonged hospitalization, and mortality. The most effective component of SSI reduction strategies is the ... ...

Abstract	Despite significant advances in infection control guidelines and practices, surgical site infections remain a substantial cause of morbidity, prolonged hospitalization, and mortality. The most effective component of SSI reduction strategies is the preoperative administration of intravenous antibiotics; however, systemic antibiotics drug exposure diminishes rapidly and may result in insufficient prophylactic activity against susceptible and resistant SSI pathogens at the wound. D-PLEX
Language	English
Publishing date	2023-06-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1154366-8
ISSN	1879-0720 ; 0928-0987
ISSN (online)	1879-0720
ISSN	0928-0987
DOI	10.1016/j.ejps.2023.106504
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Article ; Online: LymphomiRs: microRNAs with regulatory roles in lymphomas.

Kozloski, Goldi A / Lossos, Izidore S

Current opinion in hematology

2015 Volume 22, Issue 4, Page(s) 362–368

Abstract: Purpose of review: This review provides current knowledge on the role of microRNAs (miRNAs) in lymphoma with an emphasis on mature B-cell lymphoma.: Recent findings: Although miRNAs were previously used to stratify lymphoma classification, prognosis, ...

Abstract	Purpose of review: This review provides current knowledge on the role of microRNAs (miRNAs) in lymphoma with an emphasis on mature B-cell lymphoma. Recent findings: Although miRNAs were previously used to stratify lymphoma classification, prognosis, or treatment response, recent publications portray this class of small noncoding RNAs as critical players in the lymphomagenesis process. Although functional studies provide ample evidence for their role as lymphoma drivers or suppressors, genetic studies providing the underlying mechanisms for these phenotypes are still lacking. As more whole-genome sequencing of lymphoma cases become available, this gap may be soon filled. Summary: Current findings highlight the potential role of miRNAs molecules as important factors in lymphomagenesis.
MeSH term(s)	Animals ; B-Lymphocytes/metabolism ; B-Lymphocytes/pathology ; Carcinogenesis/genetics ; Carcinogenesis/metabolism ; Carcinogenesis/pathology ; Cytidine Deaminase/genetics ; Cytidine Deaminase/metabolism ; Disease Models, Animal ; Gene Expression Regulation, Neoplastic ; Germinal Center/metabolism ; Germinal Center/pathology ; Humans ; Lymphoma, B-Cell/genetics ; Lymphoma, B-Cell/metabolism ; Lymphoma, B-Cell/pathology ; Mice ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Signal Transduction
Chemical Substances	MicroRNAs ; AICDA (activation-induced cytidine deaminase) (EC 3.5.4.-) ; Cytidine Deaminase (EC 3.5.4.5)
Language	English
Publishing date	2015-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
DOI	10.1097/MOH.0000000000000157
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Article ; Online: Reduction in surgical site infections by localized administration with D-PLEX

Senagore, Anthony J / Stark, Yafit / Belotserkovsky, Olga / Reichert, Malka / Wasserberg, Nir / Tulchinsky, Hagit / Segev, Lior / Zmora, Oded / Kozloski, Goldi A / Emanuel, Noam

American journal of surgery

2022 Volume 225, Issue 3, Page(s) 485–488

Abstract: Background: D-PLEX: Patients and methods: A post-hoc analysis of a previously reported prospective randomized trial assessing D-PLEX: Results: The overall incidence of SSI was significantly lower for the D-PLEX: Conclusions: D- ... ...

Abstract	Background: D-PLEX Patients and methods: A post-hoc analysis of a previously reported prospective randomized trial assessing D-PLEX Results: The overall incidence of SSI was significantly lower for the D-PLEX Conclusions: D-PLEX
MeSH term(s)	Humans ; Surgical Wound Infection/epidemiology ; Surgical Wound Infection/prevention & control ; Surgical Wound Infection/etiology ; Anti-Bacterial Agents/therapeutic use ; Prospective Studies ; Colorectal Surgery/adverse effects ; Risk Factors ; Antibiotic Prophylaxis
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2022-11-23
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2953-1
ISSN	1879-1883 ; 0002-9610
ISSN (online)	1879-1883
ISSN	0002-9610
DOI	10.1016/j.amjsurg.2022.11.021
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Article: Conformational changes in receptor tyrosine kinase signaling: an ErbB garden of delights.

Carraway, Kermit L / Kozloski, Goldi A

F1000 biology reports

2009 Volume 1, Page(s) 72

Abstract: The ErbB family of receptor tyrosine kinases plays important roles in cell proliferation, differentiation, and apoptosis. Recent structural studies of these receptors have demonstrated dramatic conformational effects that are critical to their ligand ... ...

Abstract	The ErbB family of receptor tyrosine kinases plays important roles in cell proliferation, differentiation, and apoptosis. Recent structural studies of these receptors have demonstrated dramatic conformational effects that are critical to their ligand binding and activation, and have shown that these receptors provide levels of control beyond the classic dimerization/activation mechanism. These results indicate that this class of receptors has evolved subtle regulatory mechanisms via genetic and protein structural changes to influence their effects on cell behaviors.
Language	English
Publishing date	2009-10-22
Publishing country	England
Document type	Journal Article
ISSN	1757-594X
ISSN	1757-594X
DOI	10.3410/B1-72
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Article ; Online: Mechanistic and signaling analysis of Muc4-ErbB2 signaling module: new insights into the mechanism of ligand-independent ErbB2 activity.

Kozloski, Goldi A / Carraway, Coralie A Carothers / Carraway, Kermit L

Journal of cellular physiology

2010 Volume 224, Issue 3, Page(s) 649–657

Abstract: The membrane mucin Muc4 is aberrantly expressed in numerous epithelial carcinomas and is currently used as a cancer diagnostic and prognostic tool. Muc4 can also potentiate signal transduction by modulating differential ErbB2 phosphorylation in the ... ...

Abstract	The membrane mucin Muc4 is aberrantly expressed in numerous epithelial carcinomas and is currently used as a cancer diagnostic and prognostic tool. Muc4 can also potentiate signal transduction by modulating differential ErbB2 phosphorylation in the absence and in the presence of the ErbB3 soluble ligand heregulin (HRG-beta1). These features of Muc4 suggest that Muc4 is not merely a cancer marker, but an oncogenic factor with a unique-binding/activation relationship with the receptor ErbB2. In the present study, we examined the signaling mechanisms that are associated with the Muc4-ErbB2 module by analyzing ErbB2 differential signaling in response to Muc4 expression. Our study was carried out in the A375 human melanoma and BT-474 breast cancer cell lines as our model systems. Quantitative and comparative signaling modulations were evaluated by immunoblot using phospho-specific antibodies, and densitometry analysis. Signaling complex components were identified by chemical cross-linking, fractionation by gel filtration, immunoprecipitation, and immunoblotting. Activated downstream signaling pathways were analyzed by an antibody microarray screen and immunoblot analyses. Our results indicate that Muc4 modulates ErbB2 signaling potential significantly by stabilizing and directly interacting with the ErbB2-ErbB3 heterodimer. Further analyses indicate that Muc4 promotes ErbB2 autocatalysis, but it has no effect on ErbB3 phosphorylation, although the chemical cross-linking data indicated that the signaling module is composed of Muc4, ErbB2, and ErbB3. Our microarray analysis indicates that Muc4 expression promotes cell migration by increasing the phosphorylation of the focal adhesion kinase and also through an increase in the levels of beta-catenin.
MeSH term(s)	Animals ; Biomarkers, Tumor/metabolism ; Cell Line, Tumor ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; Humans ; Ligands ; Microarray Analysis ; Mucin-4/metabolism ; Protein Subunits/metabolism ; Receptor, ErbB-2/chemistry ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Receptor, ErbB-3/chemistry ; Receptor, ErbB-3/genetics ; Receptor, ErbB-3/metabolism ; Signal Transduction/physiology
Chemical Substances	Biomarkers, Tumor ; Ligands ; Mucin-4 ; Protein Subunits ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Receptor, ErbB-3 (EC 2.7.10.1) ; Focal Adhesion Protein-Tyrosine Kinases (EC 2.7.10.2)
Language	English
Publishing date	2010-04-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.22163
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Article ; Online: miR-181a negatively regulates NF-κB signaling and affects activated B-cell-like diffuse large B-cell lymphoma pathogenesis.

Kozloski, Goldi A / Jiang, Xiaoyu / Bhatt, Shruti / Ruiz, Jose / Vega, Francisco / Shaknovich, Rita / Melnick, Ari / Lossos, Izidore S

Blood

2016 Volume 127, Issue 23, Page(s) 2856–2866

Abstract: Distinct subgroups of diffuse large B-cell lymphoma (DLBCL) genetically resemble specific mature B-cell populations that are blocked at different stages of the immune response in germinal centers (GCs). The activated B-cell (ABC)-like subgroup resembles ... ...

Abstract	Distinct subgroups of diffuse large B-cell lymphoma (DLBCL) genetically resemble specific mature B-cell populations that are blocked at different stages of the immune response in germinal centers (GCs). The activated B-cell (ABC)-like subgroup resembles post-GC plasmablasts undergoing constitutive survival signaling, yet knowledge of the mechanisms that negatively regulate this oncogenic signaling remains incomplete. In this study, we report that microRNA (miR)-181a is a negative regulator of nuclear factor κ-light-chain enhancer of activated B-cells (NF-κB) signaling. miR-181a overexpression significantly decreases the expression and activity of key NF-κB signaling components. Moreover, miR-181a decreases DLBCL tumor cell proliferation and survival, and anti-miR-181a abrogates these effects. Remarkably, these effects are augmented in the NF-κB dependent ABC-like subgroup compared with the GC B-cell (GCB)-like DLBCL subgroup. Concordantly, in vivo analyses of miR-181a induction in xenografts results in slower tumor growth rate and prolonged survival in the ABC-like DLBCL xenografts compared with the GCB-like DLBCL. We link these outcomes to relatively lower endogenous miR-181a expression and to NF-κB signaling dependency in the ABC-like DLBCL subgroup. Our findings indicate that miR-181a inhibits NF-κB activity, and that manipulation of miR-181a expression in the ABC-like DLBCL genetic background may result in a significant change in the proliferation and survival phenotype of this malignancy.
MeSH term(s)	Animals ; B-Lymphocytes/metabolism ; B-Lymphocytes/pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Female ; Gene Expression Regulation, Neoplastic ; HEK293 Cells ; HeLa Cells ; Humans ; Lymphocyte Activation/genetics ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/pathology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; MicroRNAs/physiology ; NF-kappa B/metabolism ; Signal Transduction/genetics ; Xenograft Model Antitumor Assays
Chemical Substances	MIrn181 microRNA, human ; MicroRNAs ; NF-kappa B
Language	English
Publishing date	2016-03-03
Publishing country	United States
Document type	Journal Article ; 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-2015-11-680462
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Article ; Online: Muc4/MUC4 functions and regulation in cancer.

Carraway, Kermit L / Theodoropoulos, George / Kozloski, Goldi A / Carothers Carraway, Coralie A

Future oncology (London, England)

2010 Volume 5, Issue 10, Page(s) 1631–1640

Abstract: The membrane mucin MUC4 (human) is abundantly expressed in many epithelia, where it is proposed to play a protective role, and is overexpressed in some epithelial tumors. Studies on the rat homologue, Muc4, indicate that it acts through anti-adhesive or ... ...

Abstract	The membrane mucin MUC4 (human) is abundantly expressed in many epithelia, where it is proposed to play a protective role, and is overexpressed in some epithelial tumors. Studies on the rat homologue, Muc4, indicate that it acts through anti-adhesive or signaling mechanisms. In particular, Muc4/MUC4 can serve as a ligand/modulator of the receptor tyrosine kinase ErbB2, regulating its phosphorylation and the phosphorylation of its partner ErbB3, with or without the involvement of the ErbB3 ligand neuregulin. Muc4/MUC4 can also modulate cell apoptosis via multiple mechanisms, both ErbB2 dependent and independent. Muc4/MUC4 expression is regulated by multiple mechanisms, ranging from transcriptional to post-translational. The roles of MUC4 in tumors suggest that it may be valuable as a tumor marker or target for therapy.
MeSH term(s)	Animals ; Biomarkers, Tumor/metabolism ; Humans ; Mucin-4/metabolism ; Neoplasms/metabolism ; Rats ; Signal Transduction/physiology
Chemical Substances	Biomarkers, Tumor ; MUC4 protein, human ; Mucin-4
Language	English
Publishing date	2010-03-04
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2274956-1
ISSN	1744-8301 ; 1479-6694
ISSN (online)	1744-8301
ISSN	1479-6694
DOI	10.2217/fon.09.125
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Article ; Online: Active IKKβ promotes the stability of GLI1 oncogene in diffuse large B-cell lymphoma.

Agarwal, Nitin K / Kim, Chae H / Kunkalla, Kranthi / Konno, Hiroyasu / Tjendra, Youley / Kwon, Deukwoo / Blonska, Marzenna / Kozloski, Goldi A / Moy, Vincent T / Verdun, Ramiro E / Barber, Glen N / Lossos, Izidore S / Vega, Francisco

Blood

2015 Volume 127, Issue 5, Page(s) 605–615

Abstract: GLI1 oncogene has been implicated in the pathobiology of several neoplasms including diffuse large B-cell lymphoma (DLBCL). However, mechanisms underlying GLI1-increased activity in DLBCL are poorly characterized. Herein, we demonstrate that IKKβ ... ...

Abstract	GLI1 oncogene has been implicated in the pathobiology of several neoplasms including diffuse large B-cell lymphoma (DLBCL). However, mechanisms underlying GLI1-increased activity in DLBCL are poorly characterized. Herein, we demonstrate that IKKβ phosphorylates GLI1 in DLBCL. IKKβ activation increased GLI1 protein levels and transcriptional activity, whereas IKKβ silencing decreased GLI1 levels and transcriptional activity. Tumor necrosis factor-α (TNFα) mediated IKKβ activation-impaired GLI1 binding with the E3 ubiquitin ligase-ITCH, leading to decreased K48-linked ubiquitination/degradation of GLI1. We found 8 IKKβ-dependent phosphorylation sites that mediate GLI1 stability. Mutating or deleting these residues facilitated GLI1-ITCH interaction and decreased the protective effect of TNFα on GLI1 stability. IKKβ-GLI1 crosstalk is significant because combined inhibition of both molecules resulted in synergistic suppression of DLBCL viability in vivo and in vitro. By linking IKKβ-mediated nuclear factor-κB activity with GLI1, we identified a crosstalk between these 2 pathways that can inform the design of novel therapeutic strategies in DLBCL.
MeSH term(s)	Cell Line, Tumor ; Cell Survival ; Humans ; I-kappa B Kinase/metabolism ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/metabolism ; NF-kappa B/metabolism ; Phosphorylation ; Protein Stability ; Repressor Proteins/metabolism ; Transcription Factors/chemistry ; Transcription Factors/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination ; Zinc Finger Protein GLI1
Chemical Substances	GLI1 protein, human ; NF-kappa B ; Repressor Proteins ; Transcription Factors ; Zinc Finger Protein GLI1 ; ITCH protein, human (EC 2.3.2.26) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; I-kappa B Kinase (EC 2.7.11.10)
Language	English
Publishing date	2015-11-24
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-2015-07-658781
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Article ; Online: MicroRNAs are independent predictors of outcome in diffuse large B-cell lymphoma patients treated with R-CHOP.

Alencar, Alvaro J / Malumbres, Raquel / Kozloski, Goldi A / Advani, Ranjana / Talreja, Neha / Chinichian, Shideh / Briones, Javier / Natkunam, Yasodha / Sehn, Laurie H / Gascoyne, Randy D / Tibshirani, Rob / Lossos, Izidore S

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

2011 Volume 17, Issue 12, Page(s) 4125–4135

Abstract: Purpose: Diffuse large B-cell lymphoma (DLBCL) heterogeneity has prompted investigations for new biomarkers that can accurately predict survival. A previously reported 6-gene model combined with the International Prognostic Index (IPI) could predict ... ...

Abstract	Purpose: Diffuse large B-cell lymphoma (DLBCL) heterogeneity has prompted investigations for new biomarkers that can accurately predict survival. A previously reported 6-gene model combined with the International Prognostic Index (IPI) could predict patients' outcome. However, even these predictors are not capable of unambiguously identifying outcome, suggesting that additional biomarkers might improve their predictive power. Experimental design: We studied expression of 11 microRNAs (miRNA) that had previously been reported to have variable expression in DLBCL tumors. We measured the expression of each miRNA by quantitative real-time PCR analyses in 176 samples from uniformly treated DLBCL patients and correlated the results to survival. Results: In a univariate analysis, the expression of miR-18a correlated with overall survival (OS), whereas the expression of miR-181a and miR-222 correlated with progression-free survival (PFS). A multivariate Cox regression analysis including the IPI, the 6-gene model-derived mortality predictor score and expression of the miR-18a, miR-181a, and miR-222, revealed that all variables were independent predictors of survival except the expression of miR-222 for OS and the expression of miR-18a for PFS. Conclusion: The expression of specific miRNAs may be useful for DLBCL survival prediction and their role in the pathogenesis of this disease should be examined further.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cluster Analysis ; Cyclophosphamide/therapeutic use ; DNA Modification Methylases/genetics ; DNA Modification Methylases/metabolism ; DNA Repair Enzymes/genetics ; DNA Repair Enzymes/metabolism ; Doxorubicin/therapeutic use ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; HeLa Cells ; Humans ; Jurkat Cells ; Lymphoma, Large B-Cell, Diffuse/diagnosis ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/mortality ; Lymphoma, Large B-Cell, Diffuse/pathology ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Middle Aged ; Neoplasm Staging ; Prednisone/therapeutic use ; Prognosis ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Survival Analysis ; Treatment Outcome ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism ; Vincristine/therapeutic use ; Young Adult
Chemical Substances	FOXP1 protein, human ; Forkhead Transcription Factors ; MicroRNAs ; Repressor Proteins ; Tumor Suppressor Proteins ; Vincristine (5J49Q6B70F) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; DNA Modification Methylases (EC 2.1.1.-) ; MGMT protein, human (EC 2.1.1.63) ; DNA Repair Enzymes (EC 6.5.1.-) ; Prednisone (VB0R961HZT)
Language	English
Publishing date	2011-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-11-0224
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