Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Melanoma: HELP
Articles by Jason B. Muhitch
Based on 3 articles published since 2008
||||

Between 2008 and 2019, J. B. Muhitch wrote the following 3 articles about Melanoma.
 
+ Citations + Abstracts
1 Article Intraoperative intravital microscopy permits the study of human tumour vessels. 2016

Fisher, Daniel T / Muhitch, Jason B / Kim, Minhyung / Doyen, Kurt C / Bogner, Paul N / Evans, Sharon S / Skitzki, Joseph J. ·Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. · Department of Urology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. · Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. · Spectra Services, Incorporated, Ontario, New York 14519, USA. · Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. ·Nat Commun · Pubmed #26883450.

ABSTRACT: Tumour vessels have been studied extensively as they are critical sites for drug delivery, anti-angiogenic therapies and immunotherapy. As a preclinical tool, intravital microscopy (IVM) allows for in vivo real-time direct observation of vessels at the cellular level. However, to date there are no reports of intravital high-resolution imaging of human tumours in the clinical setting. Here we report the feasibility of IVM examinations of human malignant disease with an emphasis on tumour vasculature as the major site of tumour-host interactions. Consistent with preclinical observations, we show that patient tumour vessels are disorganized, tortuous and ∼50% do not support blood flow. Human tumour vessel diameters are larger than predicted from immunohistochemistry or preclinical IVM, and thereby have lower wall shear stress, which influences delivery of drugs and cellular immunotherapies. Thus, real-time clinical imaging of living human tumours is feasible and allows for detection of characteristics within the tumour microenvironment.

2 Article Non-redundant requirement for CXCR3 signalling during tumoricidal T-cell trafficking across tumour vascular checkpoints. 2015

Mikucki, M E / Fisher, D T / Matsuzaki, J / Skitzki, J J / Gaulin, N B / Muhitch, J B / Ku, A W / Frelinger, J G / Odunsi, K / Gajewski, T F / Luster, A D / Evans, S S. ·Department of Immunology, Roswell Park Cancer Institute, Elm &Carlton Streets, Buffalo, New York 14263, USA. · Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. · Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. · Department of Microbiology and Immunology, University of Rochester Medical Center and the Wilmot Cancer Center, Rochester, New York 14642, USA. · Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. · Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA. · Department of Pathology, University of Chicago, Chicago, Illinois 60637, USA. · Comprehensive Cancer Center and Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA. · Division of Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. ·Nat Commun · Pubmed #26109379.

ABSTRACT: T-cell trafficking at vascular sites has emerged as a key step in antitumour immunity. Chemokines are credited with guiding the multistep recruitment of CD8(+) T cells across tumour vessels. However, the multiplicity of chemokines within tumours has obscured the contributions of individual chemokine receptor/chemokine pairs to this process. Moreover, recent studies have challenged whether T cells require chemokine receptor signalling at effector sites. Here we investigate the hierarchy of chemokine receptor requirements during T-cell trafficking to murine and human melanoma. These studies reveal a non-redundant role for Gαi-coupled CXCR3 in stabilizing intravascular adhesion and extravasation of adoptively transferred CD8(+) effectors that is indispensable for therapeutic efficacy. In contrast, functional CCR2 and CCR5 on CD8(+) effectors fail to support trafficking despite the presence of intratumoral cognate chemokines. Taken together, these studies identify CXCR3-mediated trafficking at the tumour vascular interface as a critical checkpoint to effective T-cell-based cancer immunotherapy.

3 Article A novel mouse model of isolated limb perfusion for extremity melanoma. 2012

Kim, Minhyung / Camoriano, Marta / Muhitch, Jason B / Kane, John M / Skitzki, Joseph J. ·Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. ·J Surg Res · Pubmed #22494912.

ABSTRACT: BACKGROUND: Isolated limb perfusion (ILP) for extremity melanoma has been used clinically for over half a century. Mouse modeling of ILP may offer significant experimental advantages compared with existing models. We propose a novel mouse model and report our initial experience. METHODS: We injected female C57BL/6 mice (22-25 g) with 1 × 10(6) B16 melanoma cells subcutaneously in the distal right thigh. After 7 d of tumor establishment, we cannulated the superficial femoral artery (inflow) and vein (outflow) of anesthetized mice and placed a proximal tourniquet. Non-oxygenated perfusate included low-dose or high-dose melphalan and saline (control). We analyzed endpoints of cannulation time, procedural complications, morbidity, toxicity, and tumor response. RESULTS: We performed 11 superficial femoral vessel cannulations. Median cannulation time was 19 min (range, 15-32 min). Intact perfusion models were obtained in 10 of 11 cases (91%); one case failed owing to superficial femoral vein dissection. Morbidity rate was 20% (one wound dehiscence and one hematoma). Both high- and low-dose melphalan perfusion groups (4 mice/group) trended to growth delay and regression compared with saline-perfused groups. Toxicity was greater in the high-dose melphalan-treated mice. CONCLUSIONS: We have established the first reproducible mouse model of ILP for melanoma. Future experiments will take advantage of the large number of established mouse knockout models and reagents to dissect the precise mechanisms of tumor control after ILP, and examine to novel agents.