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1.
Article in English | MEDLINE | ID: mdl-31244444

ABSTRACT

Leukemia is a group of progressive hematologic malignancies derived from stem cells in bone marrow which causes a large number of cancer deaths. Even with treatment such as traditional chemotherapy, targeted therapy, and allogeneic stem cell transplantation (allo-HSCT), many patients suffer from relapse/refractory disease, and the overall survival is dismal. Leukemic stem cells (LSCs) are induced by gene mutations and undergo an aberrant and poorly regulated proliferation process which is involved in the evolution, relapse, and drug-resistance of leukemia. Emerging studies demonstrate that CD123, the interleukin 3 receptor alpha (IL-3Rα), is highly expressed in LSCs, while not normal hematopoietic stem cells (HSCs), and associates with treatment response, minimal residual disease (MRD) detection and prognosis. Furthermore, CD123 is an important marker for the identification and targeting of LSCs for refractory or relapsed leukemia. Anti-CD123 target-therapies in pre-clinical studies and clinical trials confirm the utility of anti-CD123 neutralizing antibody-drugs, CD3×CD123 bispecific antibodies, dual-affinity retargeting (DART), and anti-CD123 chimeric antigen receptor-modified T-cell (CAR-T) therapies in progress. This review summarizes the most recent progress on the study of CD123 biology and the development of novel CD123-targeted therapies.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Interleukin-3 Receptor alpha Subunit/analysis , Leukemia/diagnosis , Leukemia/therapy , Animals , Biomarkers, Tumor/analysis , Biomarkers, Tumor/antagonists & inhibitors , Humans , Immunotherapy, Adoptive , Interleukin-3 Receptor alpha Subunit/antagonists & inhibitors
2.
Cytometry B Clin Cytom ; 96(5): 368-374, 2019 09.
Article in English | MEDLINE | ID: mdl-30734478

ABSTRACT

BACKGROUND: High-grade B-cell lymphomas (HGBCL) with MYC and BCL2 or/and BCL6 rearrangements (R), so-called double/triple-hit lymphomas (DH/THL), are uncommon, clinically aggressive lymphomas that require a prompt diagnosis. We aim to identify flow cytometric immunophenotypic (IP) features of DH/THL that may aid in triaging these cases followed by a timely confirmatory cytogenetic study. METHODS: We compared the IP features of 43 cases of DH/THL to those of 55 cases of single-hit lymphoma (SHL) and 59 cases of diffuse large B-cell lymphoma (DLBCL) without MYC-R (MYCneg DLBCL). We analyzed the expression patterns of CD10, CD19, CD20, CD38, and surface immunoglobulin light chain in lymphoma cells. RESULTS: Bright CD38 expression (CD38bright ) analyzed either qualitatively or semi-quantitatively was more common in DH/THL (56%) than in MYCneg DLBCL (17%) but less common compared to SHL (82%), indicating that CD38bright can serve as a biomarker for DH/THL. Additionally, CD38bright may be a better indicator for predicting DH/THL-BCL2 than DHL-BCL6, and very bright CD38 expression was exclusive to MYC rearranged lymphomas. The expression patterns of other markers were similar among these lymphoma groups. CONCLUSIONS: CD38bright is a biomarker associated with DH/THL with a moderate sensitivity (~50%) and high specificity (~90%). While this marker cannot be used as a screening tool, awareness of this correlation may aid in expediting the diagnosis and prioritizing FISH testing in resource limited settings or situations when samples are limited. Future studies to combine immunohistochemical markers are needed to further enhance the predictive power of CD38bright in diagnosing DH/THL. © 2019 International Clinical Cytometry Society.


Subject(s)
ADP-ribosyl Cyclase 1/analysis , Biomarkers, Tumor/analysis , Flow Cytometry , Immunophenotyping , Lymphoma, B-Cell/diagnosis , Membrane Glycoproteins/analysis , ADP-ribosyl Cyclase 1/genetics , Biomarkers, Tumor/genetics , Cohort Studies , Female , Humans , Male , Membrane Glycoproteins/genetics , Sensitivity and Specificity
3.
Int J Surg Case Rep ; 30: 46-49, 2017.
Article in English | MEDLINE | ID: mdl-27902955

ABSTRACT

INTRODUCTION: Primary neuroendocrine tumors (NET) of the extrahepatic biliary tree are a rare entity with less than 100 reported cases in the literature. PRESENTATION OF CASE: Here, we report a case of NET of the extrahepatic bile duct in a 64-year-old male patient presenting with painless jaundice, direct hyperbilirubinemia, and mildly elevated transaminases. Diagnostic workup with an ultrasound revealed dilation of the intrahepatic biliary ducts, without cholelithiasis or choledocholithiasis. Additional cross sectional imaging identified a stricture at the confluence of the common hepatic and cystic duct junction. Given lack of additional findings presumptive diagnosis of localized klatskin's tumor was made. The patient subsequently underwent resection of the common bile duct and roux-en-y hepaticojejunostomy reconstruction. Final pathologic diagnosis showed G2 well-differentiated NET of the extrahepatic bile duct, measuring 1.3×1.1×1cm. DISCUSSION: When a patient is evaluated for a primary bile duct neoplasm, differentiation between cholangiocarcinoma and an unusual bile duct tumor, such as a NET is very difficult before surgical resection and histologic review. CONCLUSION: NET of the extrahepatic biliary tree are a rare entity. Typical presentation is with painless jaundice and other symptoms related to obstruction of the biliary tree and the diagnosis is usually made post-operatively.

4.
Facial Plast Surg Clin North Am ; 21(2): 265-70, 2013 May.
Article in English | MEDLINE | ID: mdl-23731587

ABSTRACT

The aging neck is accompanied by an increase in submental fat, platysmal banding, and redundant dyspigmented skin. Creating a more acute cervicomental angle, distinct mandibular border, homogeneous skin tone, and smoother texture helps to achieve a more youthful appearance. The aesthetic provider's armamentarium has long had surgical techniques in the highest regard, but a new wave of minimally invasive procedures looks to offer a nonsurgical approach to cervicomental rejuvenation. Selecting the appropriate procedure for appropriate patients that will effectively meet their aesthetic goals and expectations is the core of successful neck rejuvenation.


Subject(s)
Cosmetic Techniques , Neck , Algorithms , Botulinum Toxins, Type A/administration & dosage , Decision Support Techniques , Electric Stimulation Therapy , High-Energy Shock Waves , Humans , Intense Pulsed Light Therapy , Lasers, Solid-State , Neurotoxins/administration & dosage , Patient Selection
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