SOME BIOLOGICAL PROBLEMS IN CANCER BIOCHEMISTRY

1960 ◽  
Vol 38 (4) ◽  
pp. 425-433 ◽  
Author(s):  
Louis Siminovitch ◽  
Arthur Axelrad
Keyword(s):  
Normal Tissue ◽  
Normal Growth ◽  
Cell Types ◽  
Biological Properties ◽  
Cellular Level ◽  
Animal Cells ◽  
Biochemical Basis ◽  
Normal Tissues ◽  
Ascites Tumors

Understanding of the cancer process in chemical terms has been seriously hampered by the difficulty of interpreting results of biochemical comparisons between masses of tumor and of normal tissue. Normal tissue consists of a variety of cell types and tumors may originate from one or more of these. As whole masses, therefore, normal tissues cannot serve as adequate controls for experiments on any single tumor. Tumor cell populations, even those arising from a single cell type, are themselves cytogenetically and continually undergoing changes during growth (progression). It is thus difficult, if not impossible, to separate the relevant from the irrelevant biochemical features of malignancy.Progress in this field requires means of dealing with the problem of biological heterogeneity. Several biochemical approaches that are free from the hazards of heterogeneity and which have already yielded valuable results, or appear promising, are indicated. These include: (1) The use of ascites tumors for studying the biochemical machinery of cells. No normal tissue exists, however, that could serve as satisfactory control. (2) Biochemical comparisons between pairs of tumor lines which differ by only one inherited characteristic of malignancy. These might reveal a biochemical basis for the biological properties of tumor cells with different degrees of malignancy. (3) Elucidation of normal growth-controlling mechanisms between cells, e.g. action of hormones at the cellular level, and within cells, e.g. mechanism of feed-back control of enzymes and metabolic pathways. (4) Further research into the biochemistry of plant tumor induction in vitro. Here biochemical changes associated with inherited changes leading to nutritional autonomy and uncontrolled growth have already been demonstrated. (5) Studies on the biochemical events during induction of malignancy by viruses in clonal cultures of animal cells in vitro. These could serve as useful models of the whole process of carcinogenesis.

SOME BIOLOGICAL PROBLEMS IN CANCER BIOCHEMISTRY

1960 ◽  
Vol 38 (1) ◽  
pp. 425-433
Author(s):  
Louis Siminovitch ◽  
Arthur Axelrad
Keyword(s):  
Normal Tissue ◽  
Normal Growth ◽  
Cell Types ◽  
Biological Properties ◽  
Cellular Level ◽  
Animal Cells ◽  
Biochemical Basis ◽  
Normal Tissues ◽  
Ascites Tumors

Understanding of the cancer process in chemical terms has been seriously hampered by the difficulty of interpreting results of biochemical comparisons between masses of tumor and of normal tissue. Normal tissue consists of a variety of cell types and tumors may originate from one or more of these. As whole masses, therefore, normal tissues cannot serve as adequate controls for experiments on any single tumor. Tumor cell populations, even those arising from a single cell type, are themselves cytogenetically and continually undergoing changes during growth (progression). It is thus difficult, if not impossible, to separate the relevant from the irrelevant biochemical features of malignancy.Progress in this field requires means of dealing with the problem of biological heterogeneity. Several biochemical approaches that are free from the hazards of heterogeneity and which have already yielded valuable results, or appear promising, are indicated. These include: (1) The use of ascites tumors for studying the biochemical machinery of cells. No normal tissue exists, however, that could serve as satisfactory control. (2) Biochemical comparisons between pairs of tumor lines which differ by only one inherited characteristic of malignancy. These might reveal a biochemical basis for the biological properties of tumor cells with different degrees of malignancy. (3) Elucidation of normal growth-controlling mechanisms between cells, e.g. action of hormones at the cellular level, and within cells, e.g. mechanism of feed-back control of enzymes and metabolic pathways. (4) Further research into the biochemistry of plant tumor induction in vitro. Here biochemical changes associated with inherited changes leading to nutritional autonomy and uncontrolled growth have already been demonstrated. (5) Studies on the biochemical events during induction of malignancy by viruses in clonal cultures of animal cells in vitro. These could serve as useful models of the whole process of carcinogenesis.

Phenotypic plasticity in the intercalated cell: the hensin pathway

1998 ◽  
Vol 275 (2) ◽  
pp. F183-F190 ◽  
Author(s):  
Qais Al-Awqati ◽  
S. Vijayakumar ◽  
C. Hikita ◽  
J. Chen ◽  
J. Takito
Keyword(s):  
Collecting Duct ◽  
Basolateral Membrane ◽  
Cell Types ◽  
Band 3 ◽  
Cytoskeletal Proteins ◽  
Β Cell ◽  
Biochemical Basis ◽  
Intercalated Cell ◽  
Immortalized Cell

The collecting duct of the renal tubule contains two cell types, one of which, the intercalated cell, is responsible for acidification and alkalinization of urine. These cells exist in a multiplicity of morphological forms, with two extreme types, α and β. The former acidifies the urine by an apical proton-translocating ATPase and a basolateral Cl/HCO3 exchanger, which is an alternately spliced form of band 3. This kidney form of band 3, kAE1, is present in the apical membrane of the β-cell, which has the H+-ATPase on the basolateral membrane. We had suggested previously that metabolic acidosis leads to conversion of β-types to α-types. To study the biochemical basis of this plasticity, we used an immortalized cell line of the β-cell and showed that these cells convert to the α-phenotype when plated at superconfluent density. At high density these cells localize a new protein, which we term “hensin,” to the extracellular matrix, and hensin acts as a molecular switch capable of changing the phenotype of these cells in vitro. Hensin induces new cytoskeletal proteins, makes the cells assume a more columnar shape and retargets kAE1 and the H+-ATPase. These recent studies suggest that the conversion of β- to α-cells, at least in vitro, bears many of the hallmarks of terminal differentiation.

scholarly journals The Golgi apparatus remains associated with microtubule organizing centers during myogenesis.

1985 ◽  
Vol 101 (2) ◽  
pp. 630-638 ◽  
Author(s):  
A M Tassin ◽  
M Paintrand ◽  
E G Berger ◽  
M Bornens
Keyword(s):  
Golgi Apparatus ◽  
Nuclear Periphery ◽  
Spatial Relationship ◽  
Cell Types ◽  
Microtubule Depolymerization ◽  
Animal Cells ◽  
Microtubule Organizing Center ◽  
Microtubule Disruption ◽  
Tight Association

In vitro myogenesis involves a dramatic reorganization of the microtubular network, characterized principally by the relocalization of microtubule nucleating sites at the surface of the nuclei in myotubes, in marked contrast with the classical pericentriolar localization observed in myoblasts (Tassin, A. M., B. Maro, and M. Bornens, 1985, J. Cell Biol., 100:35-46). Since a spatial relationship between the Golgi apparatus and the centrosome is observed in most animal cells, we have decided to follow the fate of the Golgi apparatus during myogenesis by an immunocytochemical approach, using wheat germ agglutinin and an affinity-purified anti-galactosyltransferase. We show that Golgi apparatus in myotubes displays a perinuclear distribution which is strikingly different from the polarized juxtanuclear organization observed in myoblasts. As a result, the Golgi apparatus in myotubes is situated close to the microtubule organizing center (MTOC), the cis-side being situated at a fixed distance from the nuclear envelope, a situation which suggests the existence of a structural association between the Golgi apparatus and the nuclear periphery. This is supported by experiments of microtubule depolymerization by nocodazole, in which a minimal effect was observed on Golgi apparatus localization in myotubes in contrast with the dramatic scattering observed in myoblasts. In both cell types, electron microscopy reveals that microtubule disruption generates individual dictyosomes; this suggests that the connecting structures between dictyosomes are principally affected. This structural dependency of the Golgi apparatus upon microtubules is not apparently accompanied by a reverse dependency of MTOC structure or function upon Golgi apparatus activity. Golgi apparatus modification by monensin, as effective in myotubes as in myoblasts, is without apparent effect on MTOC localization or activity and on microtubule stability. The main result of our study is to show that in a cell type where the MTOC is dissociated from centrioles and where antero-posterior polarity has disappeared, the association between the Golgi apparatus and the MTOC is maintained. The significance of such a tight association is discussed.

scholarly journals Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yonatan R. Lewis-Israeli ◽  
Aaron H. Wasserman ◽  
Mitchell A. Gabalski ◽  
Brett D. Volmert ◽  
Yixuan Ming ◽  
...  
Keyword(s):  
Congenital Heart Defects ◽  
Self Assembly ◽  
Human Heart ◽  
Congenital Heart ◽  
Cardiac Development ◽  
Heart Defects ◽  
Cell Types ◽  
Cellular Level ◽  
Cardiac Tissues

AbstractCongenital heart defects constitute the most common human birth defect, however understanding of how these disorders originate is limited by our ability to model the human heart accurately in vitro. Here we report a method to generate developmentally relevant human heart organoids by self-assembly using human pluripotent stem cells. Our procedure is fully defined, efficient, reproducible, and compatible with high-content approaches. Organoids are generated through a three-step Wnt signaling modulation strategy using chemical inhibitors and growth factors. Heart organoids are comparable to age-matched human fetal cardiac tissues at the transcriptomic, structural, and cellular level. They develop sophisticated internal chambers with well-organized multi-lineage cardiac cell types, recapitulate heart field formation and atrioventricular specification, develop a complex vasculature, and exhibit robust functional activity. We also show that our organoid platform can recreate complex metabolic disorders associated with congenital heart defects, as demonstrated by an in vitro model of pregestational diabetes-induced congenital heart defects.

scholarly journals A 2020 view of tension-based cortical morphogenesis

2020 ◽  
Vol 117 (52) ◽  
pp. 32868-32879
Author(s):  
David C. Van Essen
Keyword(s):  
Cell Types ◽  
Tissue Level ◽  
Cellular Level ◽  
General Hypothesis ◽  
Cortical Gray Matter ◽  
Level I ◽  
Key Aspects ◽  
Des Model

Mechanical tension along the length of axons, dendrites, and glial processes has been proposed as a major contributor to morphogenesis throughout the nervous system [D. C. Van Essen, Nature 385, 313–318 (1997)]. Tension-based morphogenesis (TBM) is a conceptually simple and general hypothesis based on physical forces that help shape all living things. Moreover, if each axon and dendrite strive to shorten while preserving connectivity, aggregate wiring length would remain low. TBM can explain key aspects of how the cerebral and cerebellar cortices remain thin, expand in surface area, and acquire their distinctive folds. This article reviews progress since 1997 relevant to TBM and other candidate morphogenetic mechanisms. At a cellular level, studies of diverse cell types in vitro and in vivo demonstrate that tension plays a major role in many developmental events. At a tissue level, I propose a differential expansion sandwich plus (DES+) revision to the original TBM model for cerebral cortical expansion and folding. It invokes tangential tension and “sulcal zipping” forces along the outer cortical margin as well as tension in the white matter core, together competing against radially biased tension in the cortical gray matter. Evidence for and against the DES+ model is discussed, and experiments are proposed to address key tenets of the DES+ model. For cerebellar cortex, a cerebellar multilayer sandwich (CMS) model is proposed that can account for many distinctive features, including its unique, accordion-like folding in the adult, and experiments are proposed to address its specific tenets.

scholarly journals Fused Deposition Modeling 3D Printing: Test Platforms for Evaluating Post-Fabrication Chemical Modifications and In-Vitro Biological Properties

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 277 ◽  
Author(s):  
Petra Arany ◽  
Eszter Róka ◽  
Laurent Mollet ◽  
Anthony W. Coleman ◽  
Florent Perret ◽  
...  
Keyword(s):  
3D Printing ◽  
Fused Deposition Modeling ◽  
Biological Properties ◽  
Cellular Level ◽  
Poly Lactic Acid ◽  
Cytotoxicity Test ◽  
Positron Annihilation Lifetime ◽  
Fused Deposition ◽  
Surface Modified

3D printing is attracting considerable interest for its capacity to produce prototypes and small production runs rapidly. Fused deposit modeling (FDM) was used to produce polyvalent test plates for investigation of the physical, chemical, and in-vitro biological properties of printed materials. The polyvalent test plates (PVTPs) are poly-lactic acid cylinders, 14 mm in diameter and 3 mm in height. The polymer ester backbone was surface modified by a series of ramified and linear oligoamines to increase its hydrophilicity and introduce a positive charge. The chemical modification was verified by FT-IR spectroscopy, showing the introduction of amide and amine functions, and contact angle measurements confirmed increased hydrophilicity. Morphology studies (SEM, optical microscopy) indicated that the modification of PVTP possessed a planar morphology with small pits. Positron annihilation lifetime spectroscopy demonstrated that the polymeric free volume decreased on modification. An MTT-based prolonged cytotoxicity test using Caco-2 cells showed that the PVTPs are non-toxic at the cellular level. The presence of surface oligoamines on the PVTPs reduced biofilm formation by Candida albicans SC5314 significantly. The results demonstrate that 3D printed objects may be modified at their surface by a simple amidation reaction, resulting in a reduced propensity for biofilm colonization and cellular toxicity.

scholarly journals Human Mesenchymal Stromal Cell-Derived Exosomes Promote In Vitro Wound Healing by Modulating the Biological Properties of Skin Keratinocytes and Fibroblasts and Stimulating Angiogenesis

2021 ◽  
Vol 22 (12) ◽  
pp. 6239
Author(s):  
Raluca Tutuianu ◽  
Ana-Maria Rosca ◽  
Daniela Madalina Iacomi ◽  
Maya Simionescu ◽  
Irina Titorencu
Keyword(s):  
Wound Healing ◽  
Smooth Muscle Actin ◽  
Cell Types ◽  
Biological Properties ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Accelerate Wound Healing ◽  
Skin Keratinocytes ◽  
And Migration

Bone marrow-derived mesenchymal stromal cells (MSCs) are major players in regenerative therapies for wound healing via their paracrine activity, mediated partially by exosomes. Our purpose was to test if MSC-derived exosomes could accelerate wound healing by enhancing the biological properties of the main cell types involved in the key phases of this process. Thus, the effects of exosomes on (i) macrophage activation, (ii) angiogenesis, (iii) keratinocytes and dermal fibroblasts proliferation and migration, and (iv) the capacity of myofibroblasts to regulate the turnover of the extracellular matrix were evaluated. The results showed that, although exosomes did not exhibit anti-inflammatory properties, they stimulated angiogenesis. Exposure of keratinocytes and dermal (myo)fibroblasts to exosomes enhanced their proliferation and migratory capacity. Additionally, exosomes prevented the upregulation of gene expression for type I and III collagen, α-smooth muscle actin, and MMP2 and 14, and they increased MMP13 expression during the fibroblast–myofibroblast transition. The regenerative properties of exosomes were validated using a wound healing skin organotypic model, which exhibited full re-epithelialization upon exosomes exposure. In summary, these data indicate that exosomes enhance the biological properties of keratinocytes, fibroblasts, and endothelial cells, thus providing a reliable therapeutic tool for skin regeneration.

scholarly journals Infection of immune mast cells by Harvey sarcoma virus: immortalization without loss of requirement for interleukin-3.

1985 ◽  
Vol 5 (9) ◽  
pp. 2257-2264 ◽  
Author(s):  
A Rein ◽  
J Keller ◽  
A M Schultz ◽  
K L Holmes ◽  
R Medicus ◽  
...  
Keyword(s):  
Mast Cells ◽  
Cell Lines ◽  
Normal Growth ◽  
Cell Types ◽  
Growth Potential ◽  
Interleukin 3 ◽  
Sarcoma Virus ◽  
High Level

Cells from adult mouse spleens were cultured in WEHI-3 cell-conditioned medium, which contains the lymphokine interleukin-3 (IL-3). Under these conditions, cells grow well for 4 to 8 weeks; the cultures contain a variety of cell types for the first 1 to 2 weeks but are subsequently composed largely of immune mast cells. We found that infection of these cultures with Harvey sarcoma virus (HaSV) profoundly enhanced the growth potential of the cells, resulting in the reproducible isolation of long-term cell lines. These HaSV-infected cells appeared to be phenotypically identical to the immune mast cells found in uninfected cultures as determined by biochemical, immunological, and cytological tests. Although the cells expressed protein p21Ha-ras at levels similar to those in HaSV-transformed fibroblasts, they continued to require IL-3 for growth in vitro. Similar IL-3-dependent, long-term mast cell lines were also cultured from the enlarged spleens present in HaSV-infected mice. These results suggest that high-level expression of an activated Ha-ras oncogene enhances growth in these cells, perhaps by stimulating the progression of the cells into S, without affecting differentiation or altering the requirements for normal growth factor.

Transdifferentiation of chicken embryo neural retina into pigment epithelium: indications of its biochemical basis

Development ◽  
1981 ◽  
Vol 62 (1) ◽  
pp. 47-62
Author(s):  
D. J. Pritchard
Keyword(s):  
Pigment Cell ◽  
Pigment Epithelium ◽  
Cell Formation ◽  
Tca Cycle ◽  
Cell Types ◽  
Neural Retina ◽  
Pigment Cells ◽  
Biochemical Basis ◽  
Pigment Synthesis

Neural retina from 8- to 9-day embryo chickens was grown in long-term cell culture in an experiment to test the hpothesis that one step during the in vitro transdifferentiation of neural retina into pigment cells occurs in response to stimulation of tricarboxylic acid (TCA) cycle activity. Time-lapse photography showed that pigment-cell formation occurs through the intermediate stages of ‘undistinguished cells’, ‘pavement epithelium’ and ‘potential pigment cells’. Mitosis of undistinguished cells to pavement epithelium was proportional to malonate over most of the tested range of concentrations and was inhibited by succinate, which respectively depress and stimulate the TCA cycle. Conversely mitosis of pavement epithelium to potential pigment cells occurred in proportion to succinate concentration over most of the tested range and was inhibited by malonate, in support of the hypothesis under test. Melanin synthesis begins in a minority of ‘pigment leader cells’ uniquely stimulated by the lowest concentration of malonate, although higher concentrations blocked pigment synthesis in all cell types. The pigment leader cells appear to act as centres of influence upon neighbouring potential pigment cells, which subsequently also beome pigmented. Lactate inhibited most or all of the steps in formation of pigment epithelium. Between three and five mitoses occur in the production of pigment cells, whereas multilayers and lentoid bodies seem to be formed by expansion of undistinguished cells, probably without mitosis. The observations lead to a general theory that metaplastic conversion between cell types in eye tissues may require the physical isolation of overtly differentiated, multipotent cells from ‘leader’ cells which normally hold them in physiological subjugation.

scholarly journals A Multi-layer, Self-aligning Hydrogel Micro-molding Process Offering a Fabrication Route to Perfusable 3D In-Vitro Microvasculature

2018 ◽  
Author(s):  
Hossein Heidari ◽  
Hayden Taylor
Keyword(s):  
Glial Cells ◽  
3D Culture ◽  
Cell Types ◽  
Biological Properties ◽  
Vascular Networks ◽  
Mechanical Stiffness ◽  
Molding Process ◽  
Free Standing ◽  
Biological Performance

AbstractThe in-vitro fabrication of hierarchical biological systems such as human vasculature, which are made up of two or more cell types with intricate co-culture architectures, is by far one of the most complicated challenges that tissue engineers have faced. Here, we introduce a versatile method to create multi-layered, cell-laden hydrogel microstructures with coaxial geometries and heterogeneous mechanical and biological properties. The technique can be used to build in-vitro vascular networks that are fully embedded in hydrogels of physiologically realistic mechanical stiffness. Our technique produces free-standing 3D structures, eliminating rigid polymeric surfaces from the vicinity of cells and allowing layers of multiple cell types to be defined with tailored extracellular matrix (ECM) composition and stiffness, and in direct contact with each other. We demonstrate co-axial geometries with diameters ranging from 200–2000 μm and layer thicknesses as small as 50–200 µm in agarose– collagen (AC) composite hydrogels. Coaxial geometries with such fine feature sizes are beyond the capabilities of most bioprinting techniques. A potential application of such a structure is to simulate vascular networks in the brain with endothelial cells surrounded by multiple layers of pericytes and other glial cells. For this purpose, the composition and mechanical properties of the composite AC hydrogels have been optimized for cell viability and biological performance of endothelial and glial cell types in both 2D and 3D culture modes. Multi-layered vascular constructs with an endothelial layer surrounded by layers of glial cells have been fabricated. This prototype in-vitro model resembles vascular geometries and opens the way for complex multi-luminal blood vessels to be fabricated.

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