Sharif Uddin Ahmed

Bio: Sharif Uddin Ahmed is an academic researcher from University of Toronto. The author has contributed to research in topics: Cytokine & Circulating tumor cell. The author has an hindex of 21, co-authored 55 publications receiving 1431 citations. Previous affiliations of Sharif Uddin Ahmed include University Hospitals of Leicester NHS Trust & University Health Network.

Tracking the dynamics of circulating tumour cell phenotypes using nanoparticle-mediated magnetic ranking

Abstract: Profiling the heterogeneous phenotypes of rare circulating tumour cells (CTCs) in whole blood is critical to unravelling the complex and dynamic properties of these potential clinical markers. This task is challenging because these cells are present at parts per billion levels among normal blood cells. Here we report a new nanoparticle-enabled method for CTC characterization, called magnetic ranking cytometry, which profiles CTCs on the basis of their surface expression phenotype. We achieve this using a microfluidic chip that successfully processes whole blood samples. The approach classifies CTCs with single-cell resolution in accordance with their expression of phenotypic surface markers, which is read out using magnetic nanoparticles. We deploy this new technique to reveal the dynamic phenotypes of CTCs in unprocessed blood from mice as a function of tumour growth and aggressiveness. We also test magnetic ranking cytometry using blood samples collected from cancer patients.

Interrogating Circulating Microsomes and Exosomes Using Metal Nanoparticles.

Abstract: A chip-based approach for electrochemical characterization and detection of microsomes and exosomes based on direct electro-oxidation of metal nanoparticles (MNPs) that specifically recognize surface markers of these vesicles is reported. It is found that exosomes and microsomes derived from prostate cancer cells can be identified by their surface proteins EpCAM and PSMA, suggesting the potential of exosomes and microsomes for use as diagnostic biomarkers.

Aptamer and Antisense-Mediated Two-Dimensional Isolation of Specific Cancer Cell Subpopulations.

Abstract: Cancer cells, and in particular those found circulating in blood, can have widely varying phenotypes and molecular profiles despite a common origin. New methods are needed that can deconvolute the heterogeneity of cancer cells and sort small numbers of cells to aid in the characterization of cancer cell subpopulations. Here, we describe a new molecular approach to capturing cancer cells that isolates subpopulations using two-dimensional sorting. Using aptamer-mediated capture and antisense-triggered release, the new strategy sorts cells according to levels of two different markers and thereby separates them into their corresponding subpopulations. Using a phenotypic assay, we demonstrate that the subpopulations isolated have markedly different properties. This system provides an important new tool for identifying circulating tumor cell subtypes.

Multifunctional quantum dot DNA hydrogels.

Abstract: Biotemplated nanomaterials offer versatile functionality for multimodal imaging, biosensing, and drug delivery. There remains an unmet need for traceable and biocompatible nanomaterials that can be synthesized in a precisely controllable manner. Here, we report self-assembled quantum dot DNA hydrogels that exhibit both size and spectral tunability. We successfully incorporate DNA-templated quantum dots with high quantum yield, long-term photostability, and low cytotoxicity into a hydrogel network in a single step. By leveraging DNA-guided interactions, we introduce multifunctionality for a variety of applications, including enzyme-responsive drug delivery and cell-specific targeting. We report that quantum dot DNA hydrogels can be used for delivery of doxorubicin, an anticancer drug, to increase potency 9-fold against cancer cells. This approach also demonstrated high biocompatibility, trackability, and in vivo therapeutic efficacy in mice bearing xenografted breast cancer tumors. This work paves the way for the development of new tunable biotemplated nanomaterials with multiple synergistic functionalities for biomedical applications.The development of nanomaterials for imaging and drug delivery has been of great interest to the field. Here, the authors synthesized multifunctional enzyme-responsive hydrogels with self-assembling quantum dots for nucleic acid and drug delivery as well as having imaging capability.

Expression of Toll-Like Receptor 4 on Dendritic Cells Is Significant for Anticancer Effect of Dendritic Cell-Based Immunotherapy in Combination with an Active Component of OK-432, a Streptococcal Preparation

Abstract: A lipoteichoic acid-related molecule OK-PSA is an active component of OK-432, a Streptococcus -derived anticancer immunotherapeutic agent. In the present study, we first examined the effect of OK-PSA on the maturation of dendritic cells (DCs) in vitro by using the DCs derived from 5 healthy donors and 10 patients with head and neck cancer with or without expression of toll-like receptor 4 ( TLR4 ) or MD-2 mRNA. OK-PSA treatment effectively increased the surface expression of MHC class II, CD80, CD83, and CD86. OK-PSA-stimulated DCs secreted the cytokines that can induce helper T-cell 1 (Th1)-type T-cell response, and stimulated allogeneic T cells to produce IFN-γ and to elicit an allogeneic antigen-specific cytotoxicity. These activities almost depended on expression of TLR4 and MD-2 genes. We next investigated the in vivo anticancer effect of intratumoral administration of syngeneic DCs followed by OK-PSA against established tumors in mice. C57BL/6 mice, which express wild-type TLR4, and C57BL/6-derived TLR4-knockout (TLR4−/−) mice were used. Although OK-PSA accelerated the antitumor effect of intratumoral DC administration in wild-type mice bearing syngeneic tumors, the antitumor effect of OK-PSA as well as of the combination therapy with DCs and OK-PSA was not significant in TLR4−/− mice. Interestingly, an administration of wild-type-mouse-derived DCs followed by OK-PSA exhibited a marked antitumor effect even in the TLR4−/− mice. These findings suggest that OK-PSA may be a potent adjuvant for local DC therapy, and that DC therapy followed by OK-PSA is able to elicit anticancer activity even in a TLR4-deficient host when TLR4 is expressed only in DCs injected intratumorally.

Toll-like receptors and cancer.

Abstract: Toll-like receptors (TLRs) are a family of pattern recognition receptors that are best-known for their role in host defence from infection. Emerging evidence also suggests that TLRs have an important role in maintaining tissue homeostasis by regulating the inflammatory and tissue repair responses to injury. The development of cancer has been associated with microbial infection, injury, inflammation and tissue repair. Here we discuss how the function of TLRs may relate to these processes in the context of carcinogenesis.

Cancer Immunosurveillance and Immunoediting: The Roles of Immunity in Suppressing Tumor Development and Shaping Tumor Immunogenicity

Abstract: Cellular transformation and tumor development result from an accumulation of mutational and epigenetic changes that alter normal cell growth and survival pathways. For the last 100 years, there has been a vigorous debate as to whether the unmanipulated immune system can detect and eliminate such altered host derived cells despite the fact that cancer cells frequently express either abnormal proteins or abnormal levels of normal cellular proteins that function as tumor antigens. In this review, we discuss the current state of this argument and point out some of the recent key experiments demonstrating that immunity not only protects the host from cancer development (i.e., provides a cancer immunosurveillance function) but also can promote tumor growth, sometimes by generating more aggressive tumors. The terminology "cancer immunoediting" has been used to describe this dual host protective and tumor promoting action of immunity, and herein we summarize the ever-increasing experimental and clinical data that support the validity of this concept.

Electrochemical Methods for the Analysis of Clinically Relevant Biomolecules

Abstract: Rapid progress in identifying biomarkers that are hallmarks of disease has increased demand for high-performance detection technologies. Implementation of electrochemical methods in clinical analysis may provide an effective answer to the growing need for rapid, specific, inexpensive, and fully automated means of biomarker analysis. This Review summarizes advances from the past 5 years in the development of electrochemical sensors for clinically relevant biomolecules, including small molecules, nucleic acids, and proteins. Various sensing strategies are assessed according to their potential for reaching relevant limits of sensitivity, specificity, and degrees of multiplexing. Furthermore, we address the remaining challenges and opportunities to integrate electrochemical sensing platforms into point-of-care solutions.

Assigning Stereochemistry to Single Diastereoisomers by GIAO NMR Calculation: The DP4 Probability

Abstract: GIAO NMR shift calculation has been applied to the challenging task of reliably assigning stereochemistry with quantifiable confidence when only one set of experimental data are available. We have compared several approaches for assigning a probability to each candidate structure and have tested the ability of these methods to distinguish up to 64 possible diastereoisomers of 117 different molecules, using NMR shifts obtained in rapid and computationally inexpensive single-point calculations on molecular mechanics geometries without time-consuming ab initio geometry optimization. We show that a probability analysis based on the errors in each 13C or 1H shift is significantly more successful at making correct assignments with high confidence than are probabilities based on the correlation coefficient and mean absolute error parameters. Our new probability measure, which we have termed DP4, complements the probabilities obtained from our previously developed CP3 parameter, which applies to the case of assig...