Platelet Membrane-Coated and VAR2CSA Malaria Protein-Functionalized Nanoparticles for Targeted Treatment of Primary and Metastatic Cancer

2021 ◽  
Author(s):  
Min Zhou ◽  
Wenjing Lai ◽  
Guobing Li ◽  
Fengling Wang ◽  
Wuyi Liu ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Platelet Membrane ◽  
Targeted Treatment ◽  
Functionalized Nanoparticles

Analysis of the MOSAIC correlative cancer database integrating molecular cancer classification and tumor profiling to identify targeted treatment options for metastatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3121-3121
Author(s):  
Li Ma ◽  
Kai Treuner ◽  
Jenna Wong ◽  
David R. Spigel ◽  
Catherine A. Schnabel ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Genetic Alterations ◽  
Targeted Treatment ◽  
Unknown Primary ◽  
Molecular Testing ◽  
Tumor Type ◽  
Gene Assay ◽  
Biomarker Analysis ◽  
Biomarker Testing ◽  
Tumor Types

3121 Background: Unless tumor type and genetic alterations can be identified, metastatic cancer patients with unknown or uncertain diagnoses may be limited to empiric chemotherapy. The 92-gene assay (CancerTYPE ID) is a validated gene expression classifier of 50 tumor types and subtypes for patients with cancer of unknown primary (CUP) or ambiguous diagnoses. Multimodal molecular biomarker testing by next-generation sequencing (NGS), tumor mutational burden (TMB), fluorescent in situ hybridization (FISH), microsatellite instability (MSI), and immunohistochemistry (IHC) can identify genetic targets. A database integrating tumor typing with biomarker analysis in metastatic cases was utilized to identify the most prevalent genetic alterations by tumor type. Methods: MOSAIC (Molecular Synergy to Advance Individualized Cancer Care) is an IRB-approved database of cases with CancerTYPE ID testing plus multimodal biomarker testing. The current study determined molecular tumor type followed by molecular profiling by NGS for up to 323 genes, (NeoTYPE profiles, Neogenomics). Results: Tumor type was determined in 1992 of 2151 cases (92.7%), comprised of 27 different tumor types. 72% of cases were comprised of the 7 tumor types shown in the table,which also shows the frequency of the 10 most commonly mutated genes by tumor type. Bolded are genes with actionable genetic mutations for which FDA-approved therapies are not currently indicated in the identified tumor type. Conclusions: Precise targeted treatment for many patients with CUP or ambiguous diagnoses requires accurate diagnosis of the cancer origin combined with multimodal molecular testing to identify actionable genetic alterations in the appropriate cellular context. Future studies will evaluate additional biomarker profiles, including TMB, FISH, MSI, and IHC for cases in the MOSAIC database.[Table: see text]

scholarly journals Cancer Therapy: CD44v6-Peptide Functionalized Nanoparticles Selectively Bind to Metastatic Cancer Cells (Adv. Sci. 1/2017)

2017 ◽  
Vol 4 (1) ◽  
Author(s):  
Linxian Li ◽  
Mark Schmitt ◽  
Alexandra Matzke-Ogi ◽  
Parvesh Wadhwani ◽  
Veronique Orian-Rousseau ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Metastatic Cancer ◽  
Functionalized Nanoparticles ◽  
Metastatic Cancer Cells

scholarly journals CD44v6-Peptide Functionalized Nanoparticles Selectively Bind to Metastatic Cancer Cells

2016 ◽  
Vol 4 (1) ◽  
pp. 1600202 ◽  
Author(s):  
Linxian Li ◽  
Mark Schmitt ◽  
Alexandra Matzke-Ogi ◽  
Parvesh Wadhwani ◽  
Veronique Orian-Rousseau ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Metastatic Cancer ◽  
Functionalized Nanoparticles ◽  
Metastatic Cancer Cells

Visualization of the Platelet-Plasma Interface

1977 ◽  
Vol 35 ◽  
pp. 494-495
Author(s):  
D. C. Brindley ◽  
M. McGill
Keyword(s):  
Platelet Rich Plasma ◽  
Coagulation Factors ◽  
Platelet Membrane ◽  
Rabbit Platelet ◽  
Surface Coat ◽  
Special Relationship ◽  
Routine Method ◽  
Embedding Technique ◽  
Biochemical Analyses ◽  
Adsorptive Properties

Morphological and cytochemical studies of platelets have reported a surface coat, or glycocalyx, external to the plasma membrane (1). Biochemical analyses have likewise confirmed the highly adsorptive properties of platelets as transporters of coagulation factors (2). However, visualization of the platelet membrane by conventional EM procedures does not reflect this special relationship between the platelet and its plasma environment. By the routine method of alcohol-propylene oxide dehydration for Epon embedding, the lipid bilayer nature of the platelet membrane appears similar to other blood cells (Fig. 1). A new rapid embedding technique using dimethoxypropane (DMP) as dehydrating agent (13) has permitted ultrastructural analyses of the surface features of the platelet-plasma interface.Aliquots of human or rabbit platelet-rich plasma (PRP) were added to equal volumes of 6% glutaraldehyde in Millonig's buffer at 37° for 45 minutes, rinsed in buffer and postfixed in 1% osmium in Millonig's buffer for 45 minutes.

Rap1b Association with the Platelet Cytoskeleton Occurs in the Absence of Glycoproteins IIb/IIIa

1998 ◽  
Vol 79 (04) ◽  
pp. 832-836 ◽  
Author(s):  
Thomas Fischer ◽  
Christina Duffy ◽  
Gilbert White
Keyword(s):  
Molecular Weight ◽  
Divalent Cation ◽  
Binding Proteins ◽  
Binding Protein ◽  
Platelet Membrane ◽  
Low Molecular Weight ◽  
Membrane Glycoproteins ◽  
Gtp Binding Protein ◽  
Gtp Binding Proteins ◽  
Gtp Binding

SummaryPlatelet membrane glycoproteins (GP) IIb/IIIa and rap1b, a 21 kDa GTP binding protein, associate with the triton-insoluble, activation-dependent platelet cytoskeleton with similar rates and divalent cation requirement. To examine the possibility that GPIIb/IIIa was required for rap1b association with the cytoskeleton, experiments were performed to determine if the two proteins were linked under various conditions. Chromatography of lysates from resting platelets on Sephacryl S-300 showed that GPIIb/IIIa and rap1b were well separated and distinct proteins. Immunoprecipitation of GPIIb/IIIa from lysates of resting platelets did not produce rap1b or other low molecular weight GTP binding proteins and immunoprecipitation of rap1b from lysates of resting platelets did not produce GPIIb/IIIa. Finally, rap1b was associated with the activation-dependent cytoskeleton of platelets from a patient with Glanzmann’s thrombasthenia who lacks surface expressed glycoproteins IIb and IIIa. Based on these findings, we conclude that no association between GPIIb/IIIa and rap1b is found in resting platelets and that rap1b association with the activation-dependent cytoskeleton is at least partly independent of GPIIb/IIIa.

Glycoprotein Ib Has a Partial Role in Platelet-von Willebrand Factor Collagen Interaction

1988 ◽  
Vol 60 (02) ◽  
pp. 182-187 ◽  
Author(s):  
Morio Aihara ◽  
Ken Tamura ◽  
Ryuko Kawarada ◽  
Keizou Okawa ◽  
Yutaka Yoshida
Keyword(s):  
Platelet Aggregation ◽  
Von Willebrand Factor ◽  
Ricinus Communis ◽  
Protein S ◽  
Platelet Membrane ◽  
Membrane Glycoprotein ◽  
Normal Plasma ◽  
Ricinus Communis Agglutinin ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe adhesion of human fixed washed platelets (FWP) to collagen was decreased after treatment with Serratia marcescens protease (SP), which removed 95% of the glycocalicin from platelet membrane glycoprotein (GP) lb. However, the diminished adhesion of SP treated FWP to collagen could still be increased in the presence of purified von Willebrand factor (vWF). This ability of vWF to increase FWP adhesion to collagen is defined as collagen cofactor (CCo). The adhesion of FWP to collagen was not affected by a monoclonal antibody (MAb) to GP Ilb/IIIa (10E5), that inhibits ADP and collagen induced platelet aggregation. On the other hand, it was decreased by 50% by a MAb to GP lb (6D1), that inhibits ristocetin induced platelet aggregation. Adhesion of FWP in buffer to collagen was completely inhibited by Ricinus communis agglutinin I or concanavalin A, while Lens culinalis agglutinin and wheat germ agglutinin showed 50% inhibition. The FWP adhesion to collagen in the presence of vWF (normal plasma) was unaffected by MAbs to GP Ilb/IIIa (10E5, P2, HPL1) but was decreased to 32-38% by MAbs to GP lb (6D1, AN51, HPL11). A MAb to vWF (CLB-RAg 35), that inhibits ristocetin induced binding of vWF to platelets, decreased the CCo of normal plasma by 70%. The MAb, CLB-RAg 201, that inhibits the binding of vWF to collagen, completely inhibited the CCo of normal plasma. In conclusion, our data suggest that (1) GP lb has a partial role in FWP adhesion to collagen; (2) the binding of vWF to collagen is required for the expression of CCo; (3) CCo is partly mediated through GP lb; but (4) other platelet membrane protein(s) besides GP lb or GP Ilb/IIIa must also be involved in FWP-vWF-collagen interactions.

Platelet Adhesion to Native Collagens Involves Proteoglycans and May Be a Two-Step Process

1987 ◽  
Vol 58 (02) ◽  
pp. 786-789 ◽  
Author(s):  
O Behnke
Keyword(s):  
Electron Microscope ◽  
Platelet Adhesion ◽  
Close Contact ◽  
Blood Platelets ◽  
Collagen Fibrils ◽  
Platelet Membrane ◽  
Step Process ◽  
Rat Blood ◽  
Wide Gap ◽  
Rat Tail

SummaryAdhesion of rat blood platelets to native rat tail collagen fibrils was studied in the electron microscope under conditions that preserved collagen-associated proteoglycans (CAPG). The CAPG molecules were aligned in chain-like configurations that encircled the fibrils with a 65 nm period; they appeared to coat the fibrils completely and extended 60-100 nm away from the fibril. The initial platelet-fibril contact occurred between the platelet glycocalyx and the CAPG of the fibrils i.e. between two surfaces with net-negative charges. When close contact was established between the fibril surface proper and the platelet membrane, CAPG were not identified in the area of contact, and the collagen-platelet distance was reduced to a ~10-12 nm wide gap traversed by delicate links in register with fibril periodicities.

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