Immunotherapy and Prevention of Cancer by Nanovaccines Loaded with Whole‐Cell Components of Tumor Tissues or Cells

Abstract Background: Cancer is one of the leading causes of pathological death in humans. Although CTHRC1 is a prooncogene highly expressed in a variety of tumor tissues, the specific biological mechanisms of CTHRC1 involvement in cancer development need to be elucidated. Methods: In the present study, nine online bioinformatics databases were employed to explore the potential prognostic and grading value of CTHRC1 in generalized cancer as well as its potential role in regulating tumor immunity. Results: Data from GEPIA2.0, Oncomine, TNMplot, Kaplan-Meier Plotter and TISIDB database had consistently demonstrated that CTHRC1 was associated with the expression, prognosis and typing in most cancer tissues. Cbioportal and SMART analysis revealed that genomic changes and methylation of CTHRC1 in most tumor tissues. Finally, Sangerbox and TIMER database analysis suggested that CTHRC1 was involved in the changes of immune cell components in tumor immune microenvironment, with certain heterogeneity. Meanwhile, CTHRC1 was correlated with TMB, MSI, neoantigen and tumor immune checkpoint, especially CD276. Conclusion: CTHRC1 had the potential as a prognostic and grading molecular marker for pan-cancer. And CTHRC1-related targeting agents may be a novel breakthrough in tumor immunotherapy.

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The Biology of Integration of Cells into Microscale and Nanoscale Systems

Cellular Computing ◽

10.1093/oso/9780195155396.003.0013 ◽

2004 ◽

Author(s):

Michael L. Simpson ◽

Timothy E. McKnight

Keyword(s):

Cell Growth ◽

Industrial Applications ◽

Electronic Systems ◽

Nanoscale Systems ◽

Whole Cell ◽

Single Interface ◽

Structural Interface ◽

Cell Components ◽

Cellular Matrices ◽

Information Transport

In chapter 5 we focused on the informational interface between cells and synthetic components of systems. This interface is concerned with facilitating and manipulating information transport and processing between and within the synthetic and whole-cell components of these hybrid systems. However, there is also a structural interface between these components that is concerned with the physical placement, entrapment, and maintenance of the cells in a manner that enables the informational interface to operate. In this chapter we focus on this structural interface. Successful integration of whole-cell matrices into microscale and nanoscale elements requires a unique environment that fosters continued cell viability while promoting, or at least not blocking, the information transport and communication pathways described in earlier chapters. A century of cell culture has provided a wealth of insight and specific protocols to maintain the viability and (typically) proliferation of virtually every type of organism that can be propagated. More recently, the demands for more efficient bioreactors, more compatible biomedical implants, and the promise of engineered tissues has driven advances in surface-modification sciences, cellular immobilization, and scaffolding that provide structure and control over cell growth, in addition to their basic metabolic requirements. In turn, hybrid biological and electronic systems have emerged, capable of transducing the often highly sensitive and specific responses of cellular matrices for biosensing in environmental, medical, and industrial applications. The demands of these systems have driven advances in cellular immobilization and encapsulation techniques, enabling improved interaction of the biological matrix with its environment while providing nutrient and respiratory requirements for prolonged viability of the living matrices. Predominantly, such devices feature a single interface between the bulk biomatrix and transducer. However, advances in lithography, micromachining, and micro-/nanoscale synthesis provide broader opportunities for interfacing whole-cell matrices with synthetic elements. Advances in engineered, patterned, or directed cell growth are now providing spatial and temporal control over cellular integration within microscale and nanoscale systems. Perhaps the best defined integration of cellular matrices with electronically active substrates has been accomplished with neuronal patterning. Topographical and physicochemical patterning of surfaces promotes the attachment and directed growth of neurites over electrically active substrates that are used to both stimulate and observe excitable cellular activity.

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Individual and Combined Effects of Extracellular Polymeric Substances and Whole Cell Components of Chlamydomonas reinhardtii on Silver Nanoparticle Synthesis and Stability

Molecules ◽

10.3390/molecules24050956 ◽

2019 ◽

Vol 24 (5) ◽

pp. 956 ◽

Cited By ~ 10

Author(s):

Ashiqur Rahman ◽

Shishir Kumar ◽

Adarsh Bafana ◽

Si Dahoumane ◽

Clayton Jeffryes

Keyword(s):

Chlamydomonas Reinhardtii ◽

Extracellular Polymeric Substances ◽

Nanoparticle Synthesis ◽

Cell Culture Supernatant ◽

Bimodal Size Distribution ◽

Whole Cell ◽

Selected Area Electron Diffraction ◽

Cell Components ◽

Amine Groups ◽

Silver Nanoparticle Synthesis

The fresh water microalga Chlamydomonas reinhardtii bioreduced Ag+ to silver nanoparticles (AgNPs) via three biosynthetic routes in a process that could be a more sustainable alternative to conventionally produced AgNPs. The AgNPs were synthesized in either the presence of whole cell cultures, an exopolysaccharide (EPS)-containing cell culture supernatant, or living cells that had been separated from the EPS-containing supernatant and then washed before being suspended again in fresh media. While AgNPs were produced by all three methods, the washed cultures had no supernatant-derived EPS and produced only unstable AgNPs, thus the supernatant-EPS was shown to be necessary to cap and stabilize the biogenic AgNPs. TEM images showed stable AgNPs were mostly spherical and showed a bimodal size distribution about the size ranges of 3.0 ± 1.3 nm and 19.2 ± 5.0 nm for whole cultures and 3.5 ± 0.6 nm and 17.4 ± 2.6 nm for EPS only. Moreover, selected area electron diffraction pattern of these AgNPs confirmed their polycrystalline nature. FTIR of the as-produced AgNPs identified polysaccharides, polyphenols and proteins were responsible for the observed differences in the AgNP stability, size and shape. Additionally, Raman spectroscopy indicated carboxylate and amine groups were bound to the AgNP surface.

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Ultrastructure of Giant Mitochondria and Their Inclusions in Schwann Cells of Bovine Splenic Nerve

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100050986 ◽

1974 ◽

Vol 32 ◽

pp. 194-195

Author(s):

Å. Thureson-Klein

Keyword(s):

Schwann Cells ◽

Cell Organelles ◽

Giant Mitochondria ◽

Matrix Density ◽

Physiological Conditions ◽

Unmyelinated Axons ◽

Internal Structures ◽

Structural Abnormalities ◽

Cytotoxic Compounds ◽

Cell Components

Giant mitochondria of various shapes and with different internal structures and matrix density have been observed in a great number of tissues including nerves. In most instances, the presence of giant mitochondria has been associated with a known disease or with abnormal physiological conditions such as anoxia or exposure to cytotoxic compounds. In these cases degenerative changes occurred in other cell organelles and, therefore the giant mitochondria also were believed to be induced structural abnormalities.Schwann cells ensheating unmyelinated axons of bovine splenic nerve regularly contain giant mitochondria in addition to the conventional smaller type (Fig. 1). These nerves come from healthy inspected animals presumed not to have been exposed to noxious agents. As there are no drastic changes in the small mitochondria and because other cell components also appear reasonably well preserved, it is believed that the giant mitochondria are normally present jin vivo and have not formed as a post-mortem artifact.

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Further Studies on the Ultrastructure of Harderian Gland in Adult Rats

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100051451 ◽

1974 ◽

Vol 32 ◽

pp. 288-289

Author(s):

Alfredo Feria-Velasco ◽

Guadalupe Tapia-Arizmendi

Keyword(s):

Fine Structure ◽

Domestic Fowl ◽

Animal Species ◽

Acinar Cells ◽

Harderian Gland ◽

Myoepithelial Cells ◽

The Other ◽

Albino Rats ◽

Adult Rats ◽

Cell Components

The fine structure of the Harderian gland has been described in some animal species (hamster, rabbit, mouse, domestic fowl and albino rats). There are only two reports in the literature dealing on the ultrastructure of rat Harderian gland in adult animals. In one of them the author describes the myoepithelial cells in methacrylate-embbeded tissue, and the other deals with the maturation of the acinar cells and the formation of the secretory droplets. The aim of the present work is to analize the relationships among the acinar cell components and to describe the two types of cells located at the perifery of the acini.

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High-pressure freezing and freeze substitution of plant tissue

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100124148 ◽

1992 ◽

Vol 50 (1) ◽

pp. 748-749

Author(s):

William P. Sharp ◽

Robert W. Roberson

Keyword(s):

High Pressure ◽

Cell Structure ◽

Leaf Tissue ◽

Freeze Substitution ◽

Crystal Formation ◽

Ice Crystal ◽

High Pressure Freezing ◽

Cell Components ◽

Cold Metal ◽

Brome Grass

The aim of ultrastructural investigation is to analyze cell architecture and relate a functional role(s) to cell components. It is known that aqueous chemical fixation requires seconds to minutes to penetrate and stabilize cell structure which may result in structural artifacts. The use of ultralow temperatures to fix and prepare specimens, however, leads to a much improved preservation of the cell’s living state. A critical limitation of conventional cryofixation methods (i.e., propane-jet freezing, cold-metal slamming, plunge-freezing) is that only a 10 to 40 μm thick surface layer of cells can be frozen without distorting ice crystal formation. This problem can be allayed by freezing samples under about 2100 bar of hydrostatic pressure which suppresses the formation of ice nuclei and their rate of growth. Thus, 0.6 mm thick samples with a total volume of 1 mm3 can be frozen without ice crystal damage. The purpose of this study is to describe the cellular details and identify potential artifacts in root tissue of barley (Hordeum vulgari L.) and leaf tissue of brome grass (Bromus mollis L.) fixed and prepared by high-pressure freezing (HPF) and freeze substitution (FS) techniques.

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The Advantages of Cryotechniques: Application To Bioluminescent Cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010018118x ◽

1990 ◽

Vol 48 (1) ◽

pp. 486-487

Author(s):

Gisèle Nicolas ◽

Jean-Marie Bassot ◽

Marie-Thérèse Nicolas

Keyword(s):

Endoplasmic Reticulum ◽

Striated Muscle ◽

Light Emission ◽

Stable State ◽

Freeze Substitution ◽

Initial Step ◽

Point Of Interest ◽

Cell Components ◽

Excellent Preservation ◽

External Water

The use of fast-freeze fixation (FFF) followed by freeze-substitution (FS) brings substantial advantages which are due to the extreme rapidity of this fixation compared to the conventional one. The initial step, FFF, physically immobilizes most molecules and therefore arrests the biological reactions in a matter of milliseconds. The second step, FS, slowly removes the water content still in solid state and, at the same time, chemically fixes the other cell components in absence of external water. This procedure results in an excellent preservation of the ultrastructure, avoids osmotic artifacts,maintains in situ most soluble substances and keeps up a number of cell activities including antigenicities. Another point of interest is that the rapidity of the initial immobilization enables the capture of unstable structures which, otherwise, would slip towards a more stable state. When combined with electrophysiology, this technique arrests the ultrastructural modifications at a well defined state, allowing a precise timing of the events.We studied the epithelium of the elytra of the scale-worm, Harmothoe lunulata which has excitable, conductible and bioluminescent properties. The intracellular sites of the light emission are paracrystals of endoplasmic reticulum (PER), named photosomes (Fig.1). They are able to flash only when they are coupled with plasma membrane infoldings by dyadic or triadic junctions (Fig.2) basically similar to those of the striated muscle fibers. We have studied them before, during and after stimulation. FFF-FS showed that these complexes are labile structures able to diffentiate and dedifferentiate within milliseconds. Moreover, a transient network of endoplasmic reticulum was captured which we have named intermediate endoplasmic reticulum (IER) surrounding the PER (Fig.1). Numerous gap junctions are found in the membranous infoldings of the junctional complexes (Fig.3). When cryofractured, they cleave unusually (Fig.4-5). It is tempting to suggest that they play an important role in the conduction of the excitation.

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HVEM Analysis of Microfilament Patterns in The Margins of Tissue Cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600003512 ◽

1980 ◽

Vol 38 ◽

pp. 808-811

Author(s):

Carol Allen

Keyword(s):

Cell Movement ◽

Cell Spreading ◽

Living Cells ◽

Tissue Cell ◽

Large Sample Size ◽

Cell Periphery ◽

Whole Cell ◽

Critical Point Drying ◽

Lamellar Region ◽

Tissue Cells

When provided with a suitable solid substrate, tissue cells undergo a rapid conversion from the spherical form expressed in suspension culture to a characteristic flattened morphology. As a result of this conversion, called cell spreading, the cell nucleus and organelles come to occupy a central region of “deep cytoplasm” which slopes steeply into a peripheral “lamellar” region less than 1 pm thick at its outer edge and generally free of cell organelles. Cell spreading is accomplished by a continuous outward repositioning of the lamellar margins. Cell translocation on the substrate results when the activity of the lamellae on one side of the cell become dominant. When this occurs, the cell is “polarized” and moves in the direction of the “leading lamellae”. Careful analysis of tissue cell locomotion by time-lapse microphotography (1) has shown that the deformational movements of the leading lamellae occur in a repeating cycle of advance and retreat in the direction of cell movement and that the rate of such deformations are positively correlated with the speed of cell movement. In the present study, the physical basis for these movements of the cell margin has been examined by comparative light microscopy of living cells with whole-mount electron microscopy of fixed cells. Ultrastructural observations were made on tissue cells grown on Formvar-coated grids, fixed with glutaraldehyde, further processed by critical-point drying, and then photographed in the High Voltage Electron Microscope. This processing and imaging system maintains the 3-dimensional organization of the whole cell, the relationship of the cell to the substrate, and affords a large sample size which facilitates quantitative analysis. Comparative analysis of film records of living cells with the whole-cell micrographs revealed that specific patterns of microfilament organization consistently accompany recognizable stages of lamellar formation and movement. The margins of spreading cells and the leading lamellae of locomoting cells showed a similar pattern of MF repositionings (Figs. 1-4). These results will be discussed in terms of a working model for the mechanics of lamellar motility which includes the following major features: (a) lamellar protrusion results when an intracellular force is exerted at a locally weak area of the cell periphery; (b) the association of cortical MFs with one another determines the local resistance to this force; (c) where MF-to-MF association is weak, the cell periphery expands and some cortical MFs are dragged passively forward; (d) contact of the expanded area with the substrate then triggers the lateral association and reorientation of these cortical MFs into MF bundles parallel to the direction of the expansion; and (e) an active interaction between these MF bundles associated with the cortex of the expanded lamellae and the cortical MFs which remained in the sub-lamellar region then pulls the latter MFs forward toward the expanded area. Thus, the advance of the cell periphery on the substrate occurs in two stages: a passive phase in which some cortical MFs are dragged outward by the force acting to expand the cell periphery, and an active phase in which additional cortical MFs are pulled forward by interaction with the first set. Subsequent interactions between peripheral microfilament bundles and filaments in the deeper cytoplasm could then transmit the advance gained by lamellar expansion to the bulk of the cytoplasm.

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