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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue infiltrating lymphocytes isolated from the preneoplastic mouse mammary hyperneoplastic alveolar nodule (HAN) tissue line C4 express high levels of natural killer (NK) activity, which gradually wanes as spontaneous tumors develop (W. Z. Wei and G. Heppner. Br. J. Cancer, 55: 589-594, 1987). Experiments were performed to test whether modulation of NK cell activity would be associated with altered progression of HAN to tumor. Administration of polyinosinic-polycytidylic acid, which activates NK activity but does not directly affect mammary epithelial cell growth, to HAN-bearing mice enhanced tumor progression, as measured by a decrease in the latency period and increase in the incidence of mammary adenocarcinomas developing in the HAN implants. Antiasialo GM1, which reduces NK activity, reduced tumor progression. The net effect of indomethacin, which may inhibit mammary epithelial cell growth but enhances NK cell function, was to prolong the latency period of tumor development. However, this effect was reversed by interleukin 2, which activates NK cells. These findings suggest that NK activity may provide positive signals for progression of preneoplastic mammary lesions to frank neoplasia.
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PMID:Correlation of natural killer activity with tumorigenesis of a preneoplastic mouse mammary lesion. 278 36

Three independent variants with a profound reduction of cell surface H-2 have been selected from the C57BL/6 mouse-derived RBL-5 and EL-4 T lymphomas. After subcutaneous inoculation of low cell doses in syngeneic mice, the H-2- variants failed to grow out, whereas the H-2+ control lines showed progressive growth. No difference in growth rate or cloning efficiency was detectable in tissue culture. The in vivo difference in tumor outgrowth was analyzed in detail for one of the H-2-low lines. The outgrowth difference remained after the H-2-low variant and the control line had been injected subcutaneously in opposite flanks of the same mouse, and it was not dependent upon activity of mature T cells, since the same result was seen in athymic nude mice. The difference was partially sensitive to irradiation of the hosts. When mice were pretreated with anti-asialo GM1 antiserum, known to depress natural killer (NK) cell activity, the difference in outgrowth was abolished, and both the control line and the H-2- variant showed progressive growth in vivo. Experiments comparing the distribution and survival of isotope-prelabeled variant and wild type cells indicated that a rapid elimination of the former took place within 24 h after intravenous injection. These differences in tumor elimination were not seen in mice treated with anti-asialo GM1 antiserum. We conclude that the reduced tumorigenicity of sublines with impaired H-2 expression is largely, if not exclusively due to rapid elimination by NK cells. These findings may reflect an inverse, indirect relation between factors controlling H-2 expression and NK sensitivity. Another possible explanation is that major histocompatibility complex (MHC)-encoded gene products are directly involved in a regulatory signal in the NK cell system. According to this interpretation, immunological selectivity in the NK cell system would be achieved by the failure to recognize self-MHC, irrespective of the presence of foreign antigens, i.e. by detection of no-self rather than of nonself. This may also explain previous observations on H-2-linked hybrid resistance against lymphoid grafts and changes in H-2 phenotypes associated with tumor progression.
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PMID:Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism. 387 76

The effect of thymosin against tumor progression was examined in mice immunosuppressed by cytostatics or X-ray irradiation. When pretreated with cytostatic agents, such as 5-fluorouracil (5-FU) or BCNU, or by X-ray, and then inoculated with P388 or L1210 leukemias, mice died rapidly within a few days. In these systems, thymosin alpha 1 given concomitantly with the cytostatic agents or after X-irradiation prevented rapid death and extended survival, although the mice eventually died with leukemia like normal mice inoculated with cells of the same tumor. Rapid death in the 5-FU-treated mice was also prevented by adoptive transfer of spleen cells from the donor mice if these had been treated with 5-FU plus thymosin alpha 1, but not if they had received 5-FU alone. However, the restorative activity of the donor spleen cells was abrogated by treatment with anti-asialo GM1, but not by treatment with anti-Thy 1 or anti-mouse Ig serum, suggesting that the effector cells in the spleen are NK cells. In fact, thymosin alpha 1, when given concomitantly with 5-FU or after X-irradiation, maintained the NK activity of spleen, which was damaged by treatment with 5-FU or X-irradiation alone. The present study indicates that thymosin alpha 1 exerts a preventive activity against progression of leukemias at least in part through an effect on NK cells or their progenitor cells.
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PMID:Thymosin alpha 1 restores NK-cell activity and prevents tumor progression in mice immunosuppressed by cytostatics or X-rays. 655 15

The antitumor effects of interferon (IFN)-gamma were examined in two types of malignant metastatic mouse tumor cell lines following their transfection with the IFN-gamma gene by retroviral gene transfer. In both ovarian and lung tumor lines, but more markedly in the latter, subcutaneous (s.c.) tumor progression of the IFN-gamma-producing cells was profoundly suppressed in the normal syngeneic as well as in athymic nude mice. In addition, experimental metastasis via the tail vein of the IFN-gamma producers was also suppressed. Lung tumor suppression was abolished by X-irradiation of the syngeneic mice or by the administration of antiasialoganglioside GM1 antibodies into the nude mice. These results suggest that tumor suppression is due to the effect of the tumor-derived IFN-gamma on the host antitumor mechanisms including natural killer cells. Moreover, tumorigenicity of several unrelated tumor cells was significantly reduced when s.c. injected as a mixture with the apparently benign IFN-gamma-producing lung tumor cells, so that such 'non-malignant' IFN-gamma-producing cells may have therapeutic benefit against certain other malignant tumors.
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PMID:Antitumor potential of interferon-gamma: retroviral expression of mouse interferon-gamma cDNA in two kinds of highly metastatic mouse tumor lines reduces their tumorigenicity. 817 32

Aberrant and elevated ganglioside expression has been observed in neoplasms, and has been shown to be an important marker of tumor progression. We therefore studied the gangliosides of renal cell carcinoma (RCC) by analyzing gangliosides from 18 RCC biopsies, 10 RCC lines and 5 normal kidney biopsies. A comparison of tumor with normal tissue revealed a significant difference in individual ganglioside expression in which the former consistently expressed eight major gangliosides, GM3, GM2, GM1, GD3, GD1A, GD2, GD1B and GT1B, according to the nomenclature of Svennerholm. There was a notable significant mean increase in the expression of GM2, GM1 and GD1A and a significant decrease in the expression of GD3 in tumor tissue compared with normal kidney tissue. Compared with tumor biopsy tissue, RCC cell lines showed a significant decrease in the expression of GM3, but a significant increase in GM2, GM1 and GD2. There was a marked increase in a pathway gangliosides (GM2, GM1, and GD1a) in RCC biopsies and cell lines compared with normal kidney. These studies indicating that RCC have markedly aberrant ganglioside expression similar to neural origin tumors may relate to the activation of a ganglioside pathway enzymes. Gangliosides expressed on RCC tumors may be important markers of tumor progression and target antigens for immunotherapy.
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PMID:Aberrant expression of gangliosides in human renal cell carcinomas. 823 May 55

Several studies have demonstrated that transfer of oncogenes in cultured cells reproducibly induces transmissible alterations in their ganglioside profile; the transfection of the same oncogene into different cell lines and the different localization of the oncogene product result in a different ganglioside expression. In the present study the modifications of the ganglioside pattern in mammary carcinomas induced in transgenic mice by the activated form of the rat neu oncogene have been investigated. Whereas control mammary tissues contain quite exclusively GM3, all neoplastic samples show a substantial decrease of this ganglioside, an accumulation in variable amount of GM3-derived species (GM1, GD3, GD1a, GD1b, GT and GQ) and the appearance of new, not yet identified, sialic acid containing molecules. Interestingly, three out of 10 tumors analyzed, even if histologically comparable to the others but with a larger dimension, show a significative difference as regard to the GM1, GD3 and GD1a content. Our data suggest that an activated oncogene may induce also in vivo a specific and transmissible alteration in the ganglioside pattern, but this distribution could be susceptible to further modifications during the tumor progression.
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PMID:Oncogene transgenic mice: an useful model to study in vivo the relationships between gangliosides and oncogenes. 1007 7

Total body irradiation (TBI), given in low to moderate doses as a single modality, can enhance leukocyte populations and immune modifiers, resulting in slowed tumor progression. The aim of this study was to evaluate natural killer (NK) cell involvement in mediating the antitumor effect of TBI by depleting NK populations and monitoring tumor progression and immune status following exposure. C57BL/6 mice (n=54) were injected with anti-NK1.1, anti-asialo GM1, or rabbit serum prior to irradiation/tumor implantation. Selected animal groups were irradiated with a 3 Gy dose of gamma-rays and Lewis lung carcinoma (LLC) cells were subcutaneously implanted 2 h later. Tumor volumes, leukocyte populations, and cytokine levels in blood and spleen were measured up to 10 days post-irradiation/tumor implantation. Depletion of asialo GM1+ cells, but not NK1.1+ cells, led to significant acceleration of tumor growth (P<0.05). Challenge with exogenous antigens (rabbit antibodies or serum) when accompanied by administration of TBI resulted in: a) radioresistance of splenic lymphocytes, b) increased granulocyte and monocyte numbers, and c) enhanced production of IgG, IL-10, and IL-18 within plasma and tumor supernatants. Delivery of TBI to NK1.1+ depleted mice, did not show similar enhancement of leukocytes and/or their modulators. These data indicate that TBI, in conjunction with immune challenge, activates leukocyte parameters and redirects the immune system toward a T helper 2 (Th2) cell response. Additionally, NK cells are involved in mediating the antitumor effect of TBI, while challenge with exogenous protein attenuates the slowing of malignant growth that accompanies delivery of radiation. These findings also support the premise that radiation exposure can activate NK and some T cytotoxic lymphocytes, thereby leading to tumor suppression.
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PMID:NK cell depletion results in accelerated tumor growth and attenuates the antitumor effect of total body irradiation. 1461 30

Biochemistry textbooks commonly make it appear that it is a foregone conclusion that the hardware of biological information storage and transfer is confined to nucleotides and amino acids, the letters of the genetic code. However, the remarkable talents of a third class of biomolecules are often overlooked. For example, one of them far surpasses the building blocks of nucleic acids and proteins in terms of theoretical coding capacity by oligomer formation. Although often exclusively assigned to duties in energy metabolism, carbohydrates as part of cellular glycoconjugates (glycoproteins, proteoglycans, glycolipids) have, in fact, other important tasks. Currently, they are increasingly gaining recognition as an operative high-density information coding system. An elaborate enzymatic machinery enables cells to be versatile enough to produce a glycan profile (glycome) that is as characteristic as a fingerprint. Moreover, swift modifications during dynamic processes, such as differentiation or malignant transformation, are readily possible. The translation of the information presented in oligosaccharide determinants to biological responses is carried out by lectins. Recognition of foreign glycosignatures in innate immunity, regulation of cell-cell/matrix interactions, cell migration or growth, and intra- and intercellular glycan routing etc represent physiologically far-reaching lectin-carbohydrate functionality. The classification of endogenous lectins is guided by sequence alignments and conservation of distinct structural traits. For example, a jelly-roll-like folding pattern and maintenance of key residue positioning involved in stacking and C-H/pi-interactions as well as directional hydrogen bonds to the 1-galactoside ligands are common denominators among galectins. Biochemical and biophysical studies are beginning to unravel the intricacies of the selection of a limited set of endogenous ligands, such as certain integrins or ganglioside GM1, and combined with biological cell experiments, its relevance for cell sociology, e.g. in growth regulation and tumor cell invasion or activated T cell apoptosis. Histopathological monitoring accompanies the biological cell investigations, linking expression of certain family members to tumor progression or suppression. Further insights into the functional consequences of the sugar code's translation are thus expected to have notable repercussions for diagnostic and therapeutic procedures.
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PMID:The emerging functionality of endogenous lectins: A primer to the concept and a case study on galectins including medical implications. 1664 27

Gangliosides (GGs), involved in malignant alteration and tumor progression/invasiveness, are considered as tumor biomarkers or therapeutic targets. Here, we describe the first systematic GG composition characterization in human gliosarcoma versus normal brain tissue using our recently developed mass spectrometry (MS) methods, based on nano-electrospray (nano-ESI), Fourier-transform ion cyclotron resonance (FT-ICR), and chip nano-ESI quadrupole time-of-flight (QTOF), complemented by thin-layer chromatographic (TLC) analysis and quantification. Combined MS enabled detection and structural assignment of 73 distinct GG species: many more than reported so far for investigated gliomas. Apart from the 7.4-times lower total GG content, gliosarcoma contained all major brain-associated species, however, in very altered proportions, exhibiting a highly distinctive pattern: GD3 (48.9%)>GD1a/nLD1>GD2/GT3>GM3>GT1b>GM2>GM1a/GM1b/nLM1>LM1>GD1b>GQ1b. MS also revealed abundant O-Ac-GD3; its sequencing provided structural evidence to postulate a novel O-Ac-GD3 isomer O-acetylated at the inner Neu5Ac-residue, previously not structurally confirmed. The high sensitivity and mass accuracy permitted the assignment of unusual minor species: GM4, Hex-HexNAc-nLM1, Gal-GD1, Fuc-GT1, GalNAc-GT1, O-Ac-GM3, di- O-Ac-GD3O-Ac-GD3, and O-Ac-GT3, not previously reported as glioma-associated. The gliosarcoma-expressed GA2 might represent a marker distinguishing astrocytic from oligodendroglial tumors. This is, to our knowledge, so far the most complete GG composition characterization of certain glioma, which demonstrates that our MS-based approach could provide essential structural information relevant to glycosphingolipid role(s) in brain tumor biology, differential diagnosis/prognosis and novel treatment concepts.
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PMID:Human gliosarcoma-associated ganglioside composition is complex and distinctive as evidenced by high-performance mass spectrometric determination and structural characterization. 1729 53

To characterize biomarkers in neural tumors, we analyzed the acidic lipid fractions of 13 neural tumor cell lines using enzyme-linked immunoabsorbent assay (ELISA) and high-performance thin-layer chromatography (HPTLC) immunostaining. Sulfated glucuronosyl glycosphingolipids (SGGLs) are cell surface molecules that are endowed with the Human Natural Killer-1 (HNK-1) carbohydrate epitope. These glycosphingolipids (GSLs) were expressed in all cell lines with concentrations ranging from 210 to 330 ng per 2 x 10(6) cells. Sulfoglucuronosyl paragloboside (SGPG) was the prominent species with lesser amounts of sulfoglucuronosyl lactosaminyl paragloboside (SGLPG) in these tumor cell lines as assessed by quantitative HPTLC immunostaining. Among the gangliosides surveyed, GD3 and 9-O-acetylated GD3 (OAc-GD3) were expressed in all tumor cell lines. In contrast, fucosyl-GM1 was not found to restrict to small cell lung carcinoma cells. In addition, we have analyzed serum antibody titers against SGPG, GD3, and OAc-GD3 in patients with neural tumors by ELISA and HPTLC immunostaining. All sera had high titers of antibodies of the IgM isotype against SGPG (titers over 1:3,200), especially in tumors such as meningiomas, germinomas, orbital tumors, glioblastomas, medulloblastomas, and subependymomas. Serum in a patient with subependymomas also had a high anti-SGGL antibody titer of the IgG and IgA types (titers over 12,800). The titer of anti-GD3 antibody was also elevated in patients with subependymomas and medulloblastomas; the latter cases also had a high titer of antibody against OAc-GD3. Our data indicate that certain GSL antigens, especially SGGLs, GD3, and OAc-GD3, are expressed in neural tumor cells and may be considered as tumor-associated antigens that represent important biomarkers for neural tumors. Furthermore, antibody titers in sera of patients with these tumors may be of diagnostic value for monitoring the presence of tumor cells and tumor progression.
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PMID:Glycosphingolipid antigens in neural tumor cell lines and anti-glycosphingolipid antibodies in sera of patients with neural tumors. 1825 60


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