Neutrophil and Eosinophil Chemotactic Factors Released from Human Keratinocytic (Hair Follicular) Tumor Cells

3074 Background: We describe a novel immunotherapy exploiting the natural anti-Gal antibody to destroy tumors and convert them into endogenous vaccines. Anti-Gal constitutes 1% of immunoglobulins in humans and interacts specifically with a-gal epitopes (Gala1- 3Galβ1–4GlcNAc-R) on glycolipids and glycoproteins. a-Gal epitopes are abundant in nonprimate mammals. Binding of anti-Gal to a-gal epitopes on pig cells mediates xenograft rejection. We inject glycolipids carrying a-gal epitopes (a-gal glycolipids) into solid tumors. Methods: a-Gal glycolipids extracted from rabbit RBC have carbohydrate chains capped with a-gal epitopes. Efficacy of treatment was studied in a1,3galactosyltransferase knockout mice bearing B16 melanoma. These mice are unique since they lack a-gal epitopes and can produce anti- Gal, like humans. Also B16 cells lack a-gal epitopes. B16 lesions (∼5 mm) were injected with 1mg a-gal glycolipids. Results: Intratumoral injection of a-gal glycolipids results in local inflammation mediated by anti-Gal binding to the ∼2x1016 a-gal epitopes on these glycolipids, activation of complement and generation of chemotactic factors. a-Gal glycolipids insert spontaneously into tumor cell membranes. Binding of anti-Gal to a-gal epitopes on such tumor cells induces lesion destruction, similar to xenograft rejection. Anti-Gal further opsonizes tumor cells for effective uptake by inflammation recruited dendritic cells (DC), via Fcγ receptors of these APC. The DC transport internalized tumor Ags to draining lymph nodes and present tumor Ag peptides, thus activating tumor specific T cells and eliciting an immune response against micrometastases. Conclusions: Injected a-gal glycolipids effectively destroy lesions and convert them into vaccines. This treatment may be even more effective in humans, since complement activity is much higher than in mice. This treatment may also be considered as neo-adjuvant immunotherapy for converting primary tumor into autologous tumor vaccine that elicits a protective immune response against micrometastases, during the period preceding resection of the tumor. No significant financial relationships to disclose.

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The isolation of novel mesenchymal stromal cell chemotactic factors from the conditioned medium of tumor cells

Experimental Cell Research ◽

10.1016/j.yexcr.2008.07.028 ◽

2008 ◽

Vol 314 (17) ◽

pp. 3107-3117 ◽

Cited By ~ 32

Author(s):

S LIN ◽

J YANG ◽

A EVERETT ◽

C CLEVENGER ◽

M KONERU ◽

...

Keyword(s):

Conditioned Medium ◽

Tumor Cells ◽

Mesenchymal Stromal Cell ◽

Stromal Cell ◽

Chemotactic Factors

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Membranous alterations in the cytoplasm and nucleus in a primitive neuroectodermal tumor of the brain

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100084016 ◽

1978 ◽

Vol 36 (2) ◽

pp. 628-629

Author(s):

C. N. Sun ◽

C. Araoz ◽

H. J. White

Keyword(s):

Nuclear Envelope ◽

Tumor Cells ◽

Osmium Tetroxide ◽

Primitive Neuroectodermal Tumor ◽

Uranyl Acetate ◽

Neuroectodermal Tumor ◽

Annulate Lamellae ◽

Lead Citrate ◽

Thin Sections ◽

The Brain

The ultrastructure of a cerebral primitive neuroectodermal tumor has been reported previously. In the present case, we will present some unusual previously unreported membranous structures and alterations in the cytoplasm and nucleus of the tumor cells.Specimens were cut into small pieces about 1 mm3 and immediately fixed in 4% glutaraldehyde in phosphate buffer for two hours, then post-fixed in 1% buffered osmium tetroxide for one hour. After dehydration, tissues were embedded in Epon 812. Thin sections were stained with uranyl acetate and lead citrate.In the cytoplasm of the tumor cells, we found paired cisternae (Fig. 1) and annulate lamellae (Fig. 2) noting that the annulate lamellae were sometimes associated with the outer nuclear envelope (Fig. 3). These membranous structures have been reported in other tumor cells. In our case, mitochondrial to nuclear envelope fusions were often noted (Fig. 4). Although this phenomenon was reported in an oncocytoma, their frequency in the present study is quite striking.

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Ulcerogenic Tumors of the Pancreas

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100676 ◽

1968 ◽

Vol 26 ◽

pp. 186-187

Author(s):

J. C. Garancis ◽

J. F. Kuzma ◽

S. D. Wilson ◽

E. H. Ellison

Keyword(s):

Endoplasmic Reticulum ◽

Tumor Cells ◽

Islet Cell ◽

Disease Process ◽

Central Core ◽

Islet Cell Tumors ◽

Opaque Zone ◽

Granular Form ◽

Zollinger Ellison Syndrome

It has been proposed that a gastrin-like hormone elaborated by non-beta islet tumors of the pancreas may be responsible for a fulminating ulcer diathesis. Subsequently, a potent gastric secretagogue was isolated from ulcerogenic tumors of the pancreas. This disease process is known now as “Zollinger-Ellison syndrome”.In our studies of two cases of Zollinger-Ellison syndrome, pancreatic lesions were identified as alpha islet cell tumors (Fig. 1). Tumor cells were fairly uniform. The sizes of the alpha granules were not significantly different, but their number and distribution varied greatly from one cell to another. Each granule consisted of a round, highly dense central core, separated from the limiting membrane by an opaque zone. The granular form of the endoplasmic reticulum was particularly prominent. Numerous mitochondria, round or elongated, were dispersed throughout the cytoplasm. Individual or clusters of lysosomes were observed in the majority of cells.

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Glucose metabolism in cancer cells: immunogold localization of hexokinase to the outer mitochondrial membrane

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141597 ◽

1995 ◽

Vol 53 ◽

pp. 1044-1045

Author(s):

Krishan K. Arora ◽

Glenn L. Decker ◽

Peter L. Pedersen

Keyword(s):

Tumor Cells ◽

Mitochondrial Membrane ◽

Present Report ◽

Large Fraction ◽

Mitochondrial Fraction ◽

Immunogold Labeling ◽

Outer Mitochondrial Membrane ◽

Immunogold Localization ◽

Hexokinase Activity ◽

Normal Tissues

Hexokinase (ATP: D-hexose 6-phophotransferase EC 2.7.1.1) is the first enzyme of the glycolytic pathway which commits glucose to catabolism by catalyzing the phosphorylation of glucose with ATP. Previous studies have shown diat hexokinase activity is markedly elevated in rapidly growing tumor cells exhibiting high glucose catabolic rates. A large fraction (50-80%) of this enzyme activity is bound to the mitochondrial fraction (1,2) where it has preferred access to ATP (3). In contrast,the hexokinase activity of normal tissues is quite low, with one exception being brain which is a glucose-utilizing tissue (4). Biochemical evidence involving rigorous subfractionation studies have revealed striking differences between the subcellular distribution of hexokinase in normal and tumor cells [See review by Arora et al (4)].In the present report, we have utilized immunogold labeling techniques to evaluate die subcellular localization of hexokinase in highly glycolytic AS-30D hepatoma cells and in the tissue of its origin, i.e., rat liver.

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Sequential detection of mRNA for the chemokine IL-8 and macrophages (F4/80) in human melanoma

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010014141x ◽

1995 ◽

Vol 53 ◽

pp. 1008-1009

Author(s):

C.D. Bucana ◽

R. Sanchez ◽

R. Singh ◽

I.J. Fidler

Keyword(s):

Tumor Cells ◽

Nude Mice ◽

Constitutive Expression ◽

Metastatic Potential ◽

Melanoma Cells ◽

Human Melanoma ◽

Angiogenic Factor ◽

Infiltrating Cells ◽

Immunoperoxidase Assay ◽

Multifunctional Cytokine

The purpose of this study was to demonstrate by ISH the presence of IL-8 mRNA, and by immunohistochemistry (IHC) the presence of the chemokine IL-8 and the distribution of infiltrating macrophages in subcutaneous melanomas in the same tumor. IL-8 is a multifunctional cytokine produced by melanoma cells, activated macrophages and monocytes and it has been shown to be a growth and angiogenic factor for tumor cells. More recently it was shown that constitutive expression of IL-8 correlated directly with metastatic potential of human melanoma cells in nude mice. IL-8 content of a solid tumor as determined by Western blot analysis does not take into account the contribution of macrophages. Previous studies showed that murine tumors contain many infiltrating cells interspersed among tumor cells whereas human tumors growing in nude mice exhibit macrophages at the periphery or between tumor islands. In this study we demonstrate the expression of IL-8 and the distribution of macrophages by immunoperoxidase assay and IL-8 mRNA by ISH.

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Temporal and spatial interrelationships of confronting cisternae to nuclear envelope

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100125051 ◽

1992 ◽

Vol 50 (1) ◽

pp. 930-931

Author(s):

John R. Palisano

Keyword(s):

Endoplasmic Reticulum ◽

Nuclear Envelope ◽

Tumor Cells ◽

Hela Cells ◽

Microscopic Investigation ◽

Electron Microscopic Investigation ◽

Serial Sections ◽

Electron Microscopic ◽

Fetal Rat ◽

Temporal And Spatial

Although confronting cistemae (CC) have been observed in a variety of tumor cells and normal fetal rat, mouse, and human epithelial tissues, little is known about their origin or role in mitotic cells. While several investigators have suggested that CC arise from nuclear envelope (NE) folding back on itself during prophase, others have suggested that CC arise when fragments of NE pair with endoplasmic reticulum. An electron microscopic investigation of 0.25 um thick serial sections was undertaken to examine the origin of CC in HeLa cells.

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