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Article ; Online: Nanometer-scale distribution of PD-1 in the melanoma tumor microenvironment.

Comerci, Colin J / McCarthy, Dannielle G / Nosrati, Mehdi / Kim, Kevin B / Kashani-Sabet, Mohammed / Moerner, W E / Leong, Stanley P

Journal of radiology and oncology

2023 Volume 7, Issue 1, Page(s) 20–25

Abstract: The nanometer-scale spatial organization of immune receptors plays a role in cell activation and suppression. While the connection between this spatial organization and cell signaling events is emerging from cell culture experiments, how these results ... ...

Abstract	The nanometer-scale spatial organization of immune receptors plays a role in cell activation and suppression. While the connection between this spatial organization and cell signaling events is emerging from cell culture experiments, how these results translate to more physiologically relevant settings like the tumor microenvironment remains poorly understood due to the challenges of high-resolution imaging
Language	English
Publishing date	2023-05-10
Publishing country	United States
Document type	Journal Article
ISSN	2573-7724
ISSN (online)	2573-7724
DOI	10.29328/journal.jro.1001048
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Article: Recent Development of Nanomaterials for Transdermal Drug Delivery.

Leong, Moong Yan / Kong, Yeo Lee / Burgess, Kevin / Wong, Won Fen / Sethi, Gautam / Looi, Chung Yeng

Biomedicines

2023 Volume 11, Issue 4

Abstract: Nano-engineered medical products first appeared in the last decade. The current research in this area focuses on developing safe drugs with minimal adverse effects associated with the pharmacologically active cargo. Transdermal drug delivery, an ... ...

Abstract	Nano-engineered medical products first appeared in the last decade. The current research in this area focuses on developing safe drugs with minimal adverse effects associated with the pharmacologically active cargo. Transdermal drug delivery, an alternative to oral administration, offers patient convenience, avoids first-pass hepatic metabolism, provides local targeting, and reduces effective drug toxicities. Nanomaterials provide alternatives to conventional transdermal drug delivery including patches, gels, sprays, and lotions, but it is crucial to understand the transport mechanisms involved. This article reviews the recent research trends in transdermal drug delivery and emphasizes the mechanisms and nano-formulations currently in vogue.
Language	English
Publishing date	2023-04-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11041124
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Article ; Online: Oncogene-driven non-small cell lung cancers in patients with a history of smoking lack smoking-induced mutations.

Cancer research

2024

Abstract: Non-small cell lung cancers (NSCLCs) in non-smokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in non-smokers, alterations in these "non-smoking-related oncogenes" ( ... ...

Abstract	Non-small cell lung cancers (NSCLCs) in non-smokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in non-smokers, alterations in these "non-smoking-related oncogenes" (NSROs) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared to typical-smoking NSCLCs, we investigated genomic and transcriptomic alterations in 173 tumor sectors from 48 NSCLC patients. NSRO-driven NSCLCs in smokers and non-smokers had similar genomic landscapes. Surprisingly, even in patients with prominent smoking histories, the mutational signature caused by tobacco smoking was essentially absent in NSRO-driven NSCLCs, which was confirmed in two large NSCLC datasets from other geographic regions. However, NSRO-driven NSCLCs in smokers had higher transcriptomic activities related to regulation of the cell cycle. These findings suggest that, while the genomic landscape is similar between NSRO-driven NSCLC in smokers and non-smokers, smoking still affects the tumor phenotype independently of genomic alterations.
Language	English
Publishing date	2024-04-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-23-2551
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Article ; Online: Modeling Colorectal Cancer Progression Through Orthotopic Implantation of Organoids.

de Sousa E Melo, Felipe / Harnoss, Jonathan M / Kljavin, Noelyn / Scott, Ryan / Sohn, Catherine / Leong, Kevin G / de Sauvage, Frederic J

Methods in molecular biology (Clifton, N.J.)

2020 Volume 2171, Page(s) 331–346

Abstract: Colorectal cancer (CRC) related death has often been attributed to the presence of metastatic disseminated disease. A concise understanding of the molecular mechanism(s) that drive metastatic progression is therefore needed but has thus far been hampered ...

Abstract	Colorectal cancer (CRC) related death has often been attributed to the presence of metastatic disseminated disease. A concise understanding of the molecular mechanism(s) that drive metastatic progression is therefore needed but has thus far been hampered by the limited number of CRC mouse models that progress toward this disease stage. In addition, preclinical evaluation of therapeutic modalities aimed at managing metastatic disease also rests on the availability of relevant in vivo models that faithfully recapitulate the key molecular features of metastatic human CRC. To overcome these limitations, we have recently developed methodologies that enable the study of CRC progression at relevant orthotopic sites. Here, we provide a detailed methodology that describes the injection of CRC derived cell lines and organoids directly into the colorectal mucosa. This results in the growth of a single tumor mass within the colon, that can spontaneously metastasize to the liver. Furthermore, we also present a surgical procedure to directly inject cells into the portal venous circulation to induce CRC tumor growth in the liver without the requirement of a primary tumor.
MeSH term(s)	Animals ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Disease Models, Animal ; Humans ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Organoids/cytology ; Organoids/metabolism ; Xenograft Model Antitumor Assays
Language	English
Publishing date	2020-07-23
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-0747-3_23
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Article ; Online: Preclinical Characterization of XL092, a Novel Receptor Tyrosine Kinase Inhibitor of MET, VEGFR2, AXL, and MER.

Hsu, Jeff / Chong, Colin / Serrill, Jeffrey / Goon, Levina / Balayan, Joan / Johnson, Eric N / Lorenzana, Grachelle / Wu, Sharon / Leong, Kevin G / Yun, Theodore J / Wang, Yong / Jiang, Faming / Bannen, Lynne / Lamb, Peter / Xu, Wei / Yu, Peiwen

Molecular cancer therapeutics

2022 Volume 22, Issue 2, Page(s) 179–191

Abstract: The multi-receptor tyrosine kinase inhibitor XL092 has been developed to inhibit the activity of oncogenic targets, including MET, VEGFR2, and the TAM family of kinases TYRO3, AXL and MER. Presented here is a preclinical evaluation of XL092. XL092 causes ...

Abstract	The multi-receptor tyrosine kinase inhibitor XL092 has been developed to inhibit the activity of oncogenic targets, including MET, VEGFR2, and the TAM family of kinases TYRO3, AXL and MER. Presented here is a preclinical evaluation of XL092. XL092 causes a significant decrease in tumor MET and AXL phosphorylation (P < 0.01) in murine Hs 746T xenograft models relative to vehicle, and a 96% inhibition of VEGFR2 phosphorylation in murine lungs. Dose-dependent tumor growth inhibition with XL092 was observed in various murine xenograft models, with dose-dependent tumor regression seen in the NCI-H441 model. Tumor growth inhibition was enhanced with the combination of XL092 with anti-PD-1, anti-programmed death ligand-1 (PD-L1), or anti-CTLA-4 compared with any of these agents alone in the MC38 murine syngeneic model and with anti-PD-1 in the CT26 colorectal cancer survival model. In vivo, XL092 promoted a decrease in the tumor microvasculature and significant increases of peripheral CD4+ T cells and B cells and decreases in myeloid cells versus vehicle. Significant increases in CD8+ T cells were also observed with XL092 plus anti-PD-1 or anti-PD-L1 versus vehicle. In addition, XL092 promoted M2 to M1 repolarization of macrophages in vitro and inhibited primary human macrophage efferocytosis in a dose-dependent manner. In summary, XL092 was shown to have significant antitumor and immunomodulatory activity in animal models both alone and in combination with immune checkpoint inhibitors, supporting its evaluation in clinical trials.
MeSH term(s)	Humans ; Animals ; Mice ; Tyrosine Kinase Inhibitors ; Carrier Proteins ; Neoplasms ; CD8-Positive T-Lymphocytes ; Receptor Protein-Tyrosine Kinases ; Disease Models, Animal ; Cell Line, Tumor
Chemical Substances	Tyrosine Kinase Inhibitors ; Carrier Proteins ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2022-11-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-22-0262
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Zs.A 5750: Show issues

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Article ; Online: Complete Genome Sequences of

Markov, Sergei A / Church, James C / Lee, Leong / Bell, Cole M / Binkley, Sarah D / Bouma, Kevin M / Hutson, Kaitlin M / Markov, Gregory S / Mason, Elizabeth C / Rueff, Gabrielle B / Sennuga, Taiwo O / Simpson, Montana H / Zimmer, Robin J / Villalpando, Diana G

Microbiology resource announcements

2021 Volume 10, Issue 13

Abstract: This paper reports the genome sequences of bacteriophages isolated from soil samples ... ...

Abstract	This paper reports the genome sequences of bacteriophages isolated from soil samples using
Language	English
Publishing date	2021-04-01
Publishing country	United States
Document type	Journal Article
ISSN	2576-098X
ISSN (online)	2576-098X
DOI	10.1128/MRA.00209-21
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Article ; Online: Lamotrigine adjunctive therapy for refractory generalized tonic-clonic seizures.

Tjia-Leong, Eugene / Leong, Kevin / Marson, Anthony G

The Cochrane database of systematic reviews

2010 , Issue 12, Page(s) CD007783

Abstract: Background: Primary generalized tonic-clonic seizures are one of a number of generalized seizure types which also includes absence, myoclonic and atonic seizures. Effective control of tonic-clonic seizures is required to reduce the risk of injury and ... ...

Abstract	Background: Primary generalized tonic-clonic seizures are one of a number of generalized seizure types which also includes absence, myoclonic and atonic seizures. Effective control of tonic-clonic seizures is required to reduce the risk of injury and death and to improve quality of life. While most people achieve seizure control with one antiepileptic drug, around 30% do not and usually take a combination of antiepileptic drugs. Objectives: To assess the effectiveness of adjunctive lamotrigine for refractory primary generalized tonic-clonic seizures. Search strategy: We searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE (Ovid) 1950 to June 2010. No language restrictions were imposed. We also contacted GlaxoSmithKline, manufacturers of lamotrigine. Selection criteria: Randomised parallel or cross-over add-on trials of add-on lamotrigine for refractory primary generalized tonic-clonic seizures. Data collection and analysis: Outcome measures were: proportion of people (1) with 50% or greater reduction in frequency; (2) with cessation of seizures; (3) who had treatment withdrawn; (4) with adverse effects; and (5) cognitive effects; (6) quality of life outcome measures. Data were independently extracted by review authors. Main results: Two small trials were found that met the inclusion criteria. Due to differences in study design we decided not to undertake a meta-analysis. One placebo controlled cross-over trial (26 participants) showed a significant 50% reduction in tonic-clonic seizure frequency with lamotrigine. Rash was the only adverse effect causing discontinuation (N = 7). A placebo controlled parallel trial comparing 117 participants found a significant median percent reduction in tonic-clonic seizure frequency of 66.5% with lamotrigine compared with 34.2% with placebo (P = 0.006). The most common adverse events were dizziness, somnolence and nausea. Authors' conclusions: Two short term trials indicate that lamotrigine has efficacy against primary generalized tonic-clonic seizures; however, this evidence is insufficient to inform clinical practice and longer term active controlled trials are required.
MeSH term(s)	Anticonvulsants/adverse effects ; Anticonvulsants/therapeutic use ; Chemotherapy, Adjuvant/methods ; Drug Eruptions/etiology ; Epilepsy, Tonic-Clonic/drug therapy ; Exanthema/chemically induced ; Humans ; Lamotrigine ; Randomized Controlled Trials as Topic ; Triazines/adverse effects ; Triazines/therapeutic use
Chemical Substances	Anticonvulsants ; Triazines ; Lamotrigine (U3H27498KS)
Language	English
Publishing date	2010-12-08
Publishing country	England
Document type	Journal Article ; Review ; Systematic Review
ISSN	1469-493X
ISSN (online)	1469-493X
DOI	10.1002/14651858.CD007783.pub2
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Article ; Online: The Notch pathway in prostate development and cancer.

Leong, Kevin G / Gao, Wei-Qiang

Differentiation; research in biological diversity

2008 Volume 76, Issue 6, Page(s) 699–716

Abstract: The Notch family of transmembrane receptors are important mediators of cell fate determination. Accordingly, Notch signaling is intimately involved in the development of numerous tissues. Recent findings have highlighted a critical role for Notch ... ...

Abstract	The Notch family of transmembrane receptors are important mediators of cell fate determination. Accordingly, Notch signaling is intimately involved in the development of numerous tissues. Recent findings have highlighted a critical role for Notch signaling in normal prostate development. Notch signaling is required for embryonic and postnatal prostatic growth and development, for proper cell lineage specification within the prostate, as well as for adult prostate maintenance and regeneration following castration and hormone replacement. Evidence for Notch as a regulator of prostate cancer development, progression, and metastasis has also emerged. This review summarizes our current understanding of the role of Notch pathway elements, including members of the Jagged, Delta-like, hairy/enhancer-of-split, and hairy/enhancer-of-split related with YRPW motif families, in prostate development and tumorigenesis. Data supporting Notch pathway elements as oncogenes and tumor suppressors in prostate tumors, as well as data implicating Notch receptors and ligands as potential markers of normal prostate stem/progenitor cells and prostate cancer stem/initiating cells, are also presented.
MeSH term(s)	Animals ; Humans ; Male ; Neoplasms/physiopathology ; Prostate/growth & development ; Prostate/pathology ; Receptors, Notch/metabolism ; Signal Transduction ; Stem Cells/metabolism ; Stem Cells/pathology
Chemical Substances	Receptors, Notch
Language	English
Publishing date	2008-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	184540-8
ISSN	1432-0436 ; 0301-4681
ISSN (online)	1432-0436
ISSN	0301-4681
DOI	10.1111/j.1432-0436.2008.00288.x
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Zs.A 1170: Show issues

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Article ; Online: Pharmacist-led interventions for the management of medication misuse and abuse: A systematic review.

Baum, Lindsay / Badejo, Grace / Chaboyer, Kevin / Leong, Christine

Journal of the American Pharmacists Association : JAPhA

2017 Volume 57, Issue 3, Page(s) 297–298

MeSH term(s)	Community Pharmacy Services/organization & administration ; Drug Misuse/prevention & control ; Humans ; Pharmacists/organization & administration ; Prescription Drug Misuse/prevention & control ; Professional Role
Language	English
Publishing date	2017-03-06
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	2118585-2
ISSN	1544-3450 ; 1544-3191 ; 1086-5802
ISSN (online)	1544-3450
ISSN	1544-3191 ; 1086-5802
DOI	10.1016/j.japh.2017.01.012
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Zs.A 1042: Show issues

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Article ; Online: Arrhythmic Risk in Biventricular Pacing Compared With Left Bundle Branch Area Pacing: Results From the I-CLAS Study.

Herweg, Bengt / Sharma, Parikshit S / Cano, Óscar / Ponnusamy, Shunmuga Sundaram / Zanon, Francesco / Jastrzebski, Marek / Zou, Jiangang / Chelu, Mihail G / Vernooy, Kevin / Whinnett, Zachary I / Nair, Girish M / Molina-Lerma, Manuel / Curila, Karol / Zalavadia, Dipen / Dye, Cicely / Vipparthy, Sharath C / Brunetti, Ryan / Mumtaz, Mishal / Moskal, Pawel /

Leong, Andrew M / van Stipdonk, Antonius / George, Jerin / Qadeer, Yusuf K / Kolominsky, Jeffrey / Golian, Mehrdad / Morcos, Ramez / Marcantoni, Lina / Subzposh, Faiz A / Ellenbogen, Kenneth A / Vijayaraman, Pugazhendhi

Circulation

2023 Volume 149, Issue 5, Page(s) 379–390

Abstract: Background: Left bundle branch area pacing (LBBAP) may be associated with greater improvement in left ventricular ejection fraction and reduction in death or heart failure hospitalization compared with biventricular pacing (BVP) in patients requiring ... ...

Abstract	Background: Left bundle branch area pacing (LBBAP) may be associated with greater improvement in left ventricular ejection fraction and reduction in death or heart failure hospitalization compared with biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy. We sought to compare the occurrence of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and new-onset atrial fibrillation (AF) in patients undergoing BVP and LBBAP. Methods: The I-CLAS study (International Collaborative LBBAP Study) included patients with left ventricular ejection fraction ≤35% who underwent BVP or LBBAP for cardiac resynchronization therapy between January 2018 and June 2022 at 15 centers. We performed propensity score-matched analysis of LBBAP and BVP in a 1:1 ratio. We assessed the incidence of VT/VF and new-onset AF among patients with no history of AF. Time to sustained VT/VF and time to new-onset AF was analyzed using the Cox proportional hazards survival model. Results: Among 1778 patients undergoing cardiac resynchronization therapy (BVP, 981; LBBAP, 797), there were 1414 propensity score-matched patients (propensity score-matched BVP, 707; propensity score-matched LBBAP, 707). The occurrence of VT/VF was significantly lower with LBBAP compared with BVP (4.2% versus 9.3%; hazard ratio, 0.46 [95% CI, 0.29-0.74]; Conclusions: LBBAP was associated with a lower incidence of sustained VT/VF and new-onset AF compared with BVP. This difference remained significant after adjustment for differences in baseline characteristics between patients with BVP and LBBAP. Physiological resynchronization by LBBAP may be associated with lower risk of arrhythmias compared with BVP.
MeSH term(s)	Humans ; Cardiac Resynchronization Therapy/adverse effects ; Stroke Volume ; Ventricular Function, Left ; Treatment Outcome ; Tachycardia, Ventricular/epidemiology ; Tachycardia, Ventricular/etiology ; Tachycardia, Ventricular/therapy ; Ventricular Fibrillation/epidemiology ; Ventricular Fibrillation/etiology ; Ventricular Fibrillation/therapy ; Heart Failure/epidemiology ; Heart Failure/therapy ; Electrocardiography
Language	English
Publishing date	2023-11-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.123.067465
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