Publications by authors named "Mandi Wang"

Fused in sarcoma (FUS), a multifunctional deoxyribonucleic acid (DNA)/ribonucleic acid (RNA)-binding protein, has been implicated in various cancer types, including sarcoma and leukemia. Despite its association with these diseases, there has been limited exploration of FUS as a cancer therapy target, primarily because its dynamic nature makes it difficult to target specifically. In this study, we explored a kind of β-sheet peptide foldamer, named β-TAT, to influence FUS aggregation by targeting its RNA recognition motifs (RRM).

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Immune checkpoint blockade therapy represented by programmed cell death ligand 1 (PD-L1) inhibitor for advanced renal carcinoma with an objective response rate (ORR) in patients is less than 20%. It is attributed to abundant tumoral vasculature with abnormal structure limiting effector T cell infiltration and drug penetration. We propose a bispecific fibrous glue (BFG) to regulate tumor immune and vascular microenvironments simultaneously.

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(1) Background: , a valuable medicinal fungus, has limited studies on its gene function due to the lack of a genetic transformation system. (2) Methods: This study aimed to establish an efficient -mediated transformation (ATMT) system for This study involved cloning the promoter (glyceraldehyde-3-phosphate dehydrogenase, ) of , reconstructing the transformation vector, optimizing the treatment of receptor tissues, and inventing a new method for screening positive transformants. (3) Results: The established ATMT system involved replacing the CaMV35S promoter of pCAMBIA-1301 with the promoter of to construct the pCAMBIA-SH- transformation vector.

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Protein complexes are highly dynamic entities that display substantial diversity in their assembly, post-translational modifications, and non-covalent interactions, allowing them to play critical roles in various biological processes. The heterogeneity, dynamic nature, and low abundance of protein complexes in their native states present challenges to study using conventional structural biology techniques. Here we develop a native nanoproteomics strategy for the enrichment and subsequent native top-down mass spectrometry (nTDMS) analysis of endogenous cardiac troponin (cTn) complex directly from human heart tissue.

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Background: Radiomics analysis could provide complementary tissue characterization in ovarian cancer (OC). However, OC segmentation required in radiomics analysis is time-consuming and labour-intensive. In this study, we aim to evaluate the performance of deep learning-based segmentation of OC on contrast-enhanced CT images and the stability of radiomics features extracted from the automated segmentation.

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Article Synopsis
  • PROTACs are a new drug development approach that targets and degrades specific proteins, but face challenges like off-target effects and the "hook effect."
  • Researchers have introduced Nano-PROTACs, which can self-assemble inside tumor cells and effectively degrade proteins in a controlled manner, avoiding the hook effect.
  • These Nano-PROTACs have shown a high degradation rate (95%) for proteins like EGFR and AR in lab tests, and have successfully inhibited tumor growth in mice models, suggesting potential for clinical applications.
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  • Anti-PD-L1 monoclonal antibodies have shown success in empowering T-cells for tumor immunotherapy, but challenges remain due to low T-cell infiltration and high levels of extracellular matrix hindering effectiveness.
  • A new peptide-based bispecific nanoblocker (BNB) strategy is designed to target CXCR4 and PD-L1, helping increase T-cell infiltration and activation by forming nanoclusters directly on tumor cells.
  • The BNB demonstrates a significantly longer half-life in tumors compared to plasma, leading to better tumor accumulation and fewer side effects, ultimately improving immunotherapy outcomes by reducing tumor stress from matrix components.
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Protein complexes are highly dynamic entities that display substantial diversity in their assembly, post-translational modifications, and non-covalent interactions, allowing them to play critical roles in various biological processes. The heterogeneity, dynamic nature, and low abundance of protein complexes in their native states present tremendous challenges to study using conventional structural biology techniques. Here we develop a "native nanoproteomics" strategy for the native enrichment and subsequent native top-down mass spectrometry (nTDMS) of low-abundance protein complexes.

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Protein complexes are highly dynamic entities that display substantial diversity in their assembly, post-translational modifications, and non-covalent interactions, allowing them to play critical roles in various biological processes. The heterogeneity, dynamic nature, and low abundance of protein complexes in their native states present tremendous challenges to study using conventional structural biology techniques. Here we develop a "native nanoproteomics" strategy for the native enrichment and subsequent native top-down mass spectrometry (nTDMS) of low-abundance protein complexes.

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Article Synopsis
  • * A new treatment called bispecific glycopeptide (bsGP) targets both tumor-associated macrophages (TAMs) and tumor cells, helping to convert harmful TAMs into beneficial immune cells.
  • * In bladder tumor models, bsGP significantly decreased the recurrence rate to 22%, compared to much higher rates with traditional treatments, suggesting it may effectively combat cancer spread and improve immune response.
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Importance: Epithelial ovarian carcinoma is heterogeneous and classified according to the World Health Organization Tumour Classification, which is based on histologic features and molecular alterations. Preoperative prediction of the histologic subtypes could aid in clinical management and disease prognostication.

Objective: To assess the value of radiomics based on contrast-enhanced computed tomography (CT) in differentiating histologic subtypes of epithelial ovarian carcinoma in multicenter data sets.

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Lysosome-targeting self-assembling prodrugs had emerged as an attractive approach to overcome the acquisition of resistance to chemotherapeutics by inhibiting lysosomal sequestration. Taking advantage of lysosomal acidification induced intracellular hydrolytic condensation, we developed a lysosomal-targeting self-condensation prodrug-nanoplatform () system for overcoming lysosome-mediated drug resistance. Briefly, the designed hydroxycamptothecine (HCPT)-silane conjugates self-assembled into silane-based nanoparticles, which were taken up into lysosomes by tumor cells.

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Article Synopsis
  • Tumor cells modify their metabolism to increase glycolytic metabolites, which aids in their growth and proliferation.
  • The study focuses on a new PKM2 nano-activator that promotes the conversion of the PKM2 enzyme from dimers to tetramers, effectively slowing down glycolysis and inhibiting tumor growth and spread.
  • This glycopeptide-based nano-activator targets tumors directly and enhances the effectiveness of chemotherapy in treating prostate and breast cancers by disrupting tumor metabolism.
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Article Synopsis
  • * A new imaging strategy was developed that utilizes MMP-2 to enhance how these agents stick to tumors, improving their retention time and increasing the signal-to-noise ratio (SNR) during imaging.
  • * Tests showed this advanced strategy successfully accumulated at tumor sites in models of renal cell carcinoma and hepatocellular carcinoma, making it a promising tool for better tumor imaging in complex surgeries.
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Intravesical administration of first-line drugs has shown failure in the treatment of bladder cancer owing to the poor tumor retention time of chemotherapeutics. Herein, we report an intracellular hydrolytic condensation (IHC) system to construct long-term retentive nano-drug depots in situ, wherein sustained drug release results in highly efficient suppression of bladder cancer. Briefly, the designed doxorubicin (Dox)-silane conjugates self-assemble into silane-based prodrug nanoparticles, which condense into silicon particle-based nano-drug depots inside tumor cells.

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Chemoimmunotherapy using nanotechnology has shown great potential for cancer therapy in the clinic. However, uncontrolled transportation and synergistic responses remain challenges. Here, a self-assembled selenopeptide nanoparticle that strengthens tumor chemoimmunotherapy through the activation of natural killer (NK) cells by the oxidative metabolite of the selenopeptide is developed.

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Article Synopsis
  • Researchers developed a programmable peptide molecule that enhances protein function by promoting specific self-assembly through receptor targeting in cells.
  • The study focused on a peptide named G7-RGD that specifically binds to the integrin αβ receptor, resulting in a significant decrease in the concentration needed for the peptide to self-assemble effectively.
  • A novel bispecific peptide, antiCD3-G7-RGD, was created to improve cancer immunotherapy by activating T cells through CD3 oligomerization, which aids in attacking cancer cells.
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Modulated molecular design-based intracellular self-assembly strategy has showed great potentiality in drug delivery, due to its assembling nature-resulted optimized drug biodistribution and metabolism. The modular designing concept endows the delivery system multiple functions, such as, selectivity and universality to improve the pharmacokinetics of loaded drugs. However, the accurate controlling of the self-assembling process in desired site to achieve optimal drug delivery is posed great challenges toward rational molecular design.

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Article Synopsis
  • Peptide drug conjugates (PDCs) are a new type of cancer treatment that offer better targeting and fewer side effects compared to traditional chemotherapy, but they struggle with penetrating tumor cells.
  • The research presents a new PDC design that includes a targeting motif, an assembly motif, and a cytotoxic payload, which creates nanoclusters that enhance the drug's effectiveness in entering cells.
  • Testing in breast and bladder cancer models showed that this PDC not only improves treatment efficacy but also allows for higher doses of the drug to be tolerated, highlighting its potential for advancing PDC development.
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Rationale And Objectives: Clinicopathological characteristics including histological subtypes, tumour grades and International Federation of Gynecology and Obstetrics (FIGO) stages are crucial factors in the clinical decision for cervical carcinoma (CC). The purpose of this study was to evaluate the ability of T2-weighted imaging (T2WI) and diffusion kurtosis imaging (DKI) radiomics in differentiating clinicopathological characteristics of CC.

Materials And Methods: One hundred and seventeen histologically confirmed CC patients (mean age 56.

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Background: Magnetic resonance fingerprinting (MRF) is a fast-imaging acquisition technique that generates quantitative and co-registered parametric maps. The aim of this feasibility study was to evaluate the agreement between MRF and phantom reference values, scan-rescan repeatability of MRF in normal cervix, and its ability to distinguish cervical carcinoma (CC) from normal cervical tissues.

Methods: An International Society of Magnetic Resonance in Medicine/National Institute of Standards and Technology (ISMRM/NIST) phantom was scanned using MRF 15 times over 65 days.

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Objective: To examine the associations of intravoxel incoherent motion (IVIM) parameters with treatment response in cervical cancer following concurrent chemoradiotherapy (CCRT).

Materials And Methods: Forty-five patients, median age of 58 years (range: 28-82), with pre-CCRT and post-CCRT MRI, were retrospectively analysed. The IVIM parameters pure diffusion coefficient (D) and perfusion fraction (f) were estimated using the full b-value distribution (BVD) as well as an optimised subsample BVD.

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Objective: To examine the associations of histogram features of T2-weighted (T2W) images and apparent diffusion coefficient (ADC) with treatment response in locally advanced cervical cancer (LACC) following concurrent chemoradiotherapy (CCRT).

Materials And Methods: Fifty-eight patients who underwent a 4-week CCRT regimen with MRI prior to treatment (pre-CCRT) and after treatment (post-CCRT) were retrospectively analysed. Histogram features were calculated from volumes of interest (VOIs) from one radiologist on T2W images and ADC maps.

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One of the major challenges of immune checkpoint blockade (ICB) is the poor penetration of antibody for solid tumor treatment. Herein, peptides with deeper penetration capability are used to develop a click reaction-assisted peptide immune checkpoint blockade (CRICB) strategy that could construct assemblies, enabling enhanced accumulation and prolonged PD-L1 occupancy, ultimately realizing high-performance tumor inhibition. First, the free DBCO-modified targeting peptide (TP) efficiently recognizes and binds PD-L1 in a deep solid tumor.

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Objectives: To evaluate MRI texture analysis in differentiating clinicopathological characteristics of cervical carcinoma (CC).

Methods: Patients with newly diagnosed CC who underwent pre-treatment MRI were retrospectively reviewed. Texture analysis was performed using commercial software (TexRAD).

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