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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The way in which melanoma cells invade the initial lymphatics of the skin was investigated in this study. Samples of sixty melanomas were examined by transmission electron microscopy. Tumor cells invading lymph vessels were demonstrated in 20 specimens. In most cases the melanomas penetrated the subendothelial space as single cells. These fused with the endothelial cytoplasmic membrane and subsequently destroyed the endothelial wall.
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PMID:Ultrastructural studies on the invasion of melanomas in initial lymphatics of human skin. 172 41

Similar to growth factors aldosterone stimulates Na+/H+ exchange in renal target cells leading to cytoplasmic alkalinization. An alkaline intracellular pH reduces the H+ bonds between repressor proteins and DNA leading to the destabilization of the nuclear chromatin. We observed that sustained alkaline stress "per se" can lead to malignant transformation of Madin-Darby canine kidney (MDCK) cells. Cells grown for two weeks in alkaline culture medium (pH 7.8) developed multiple "foci" composed of spindle-shaped pleomorphic cells lacking contact inhibition and exhibiting poor adhesion to the culture support, typical characteristics of dedifferentiated tumor cells. "Focus" cells were cloned and grown in standard medium (pH 7.4). Cells maintained their abnormal growth pattern, indicating stable pH-induced genetic transformation. Cells were fused with polyethylene glycol to giant cells and impaled with microelectrodes. In contrast to non-transformed giant MDCK cells the plasma membrane potential showed spontaneous oscillations that could be virtually abolished by the omission of extracellular Ca2+ or by the addition of the K+ channel blocker Ba2+. We conclude that sustained alkaline stress can induce malignant transformation in MDCK cells indicated by an abnormal growth pattern and by membrane potential oscillations most likely due to Ca2+ activated K+ channels in the plasma membrane.
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PMID:Alkaline stress transforms Madin-Darby canine kidney cells. 174 13

Surgical treatment of neuropathic spinal arthropathy is traditionally associated with a high rate of complication. Ten patients were treated surgically using contemporary techniques of spinal instrumentation and fusion which included combined anterior and posterior procedures when appropriate. The etiology of the spinal arthropathy was fracture (8 patients) and tumor (2 patients). Mean postsurgical follow-up was 4 years. Solid arthrodesis was obtained in eight patients. Our recommendations for surgical treatment include (a) posterior segmental instrumentation and fusion for single level Charcot involvement, with bone grafting of the anterior single level defect accomplished through the posterolateral approach; (b) restoration of normal sagittal plane contour, with anterior first stage surgery recommended for rigid kyphosis or multiple level Charcot involvement; and (c) leaving no intercurrent unfused segments between new and old fusions in the area of neurologic deficit. Fusion to the pelvis is not always necessary but late arthropathy may develop between the fused segment and the pelvis.
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PMID:Surgical treatment of neuropathic spinal arthropathy. 180 63

Variable screw placement (VSP) plates and pedicle screw fixation were used to stabilize eleven lumbar neoplasms. Blood loss and complications were comparable to other methods of posterior segmental fixation, although operative times were longer. Fewer levels were fused than for systems using sublaminar hooks or wires, with 8/11 patients treated with two level fixation. Four preoperatively irradiated patients experienced 43% of all complications and had 70% of the major complications. Wound infections occurred in 18%, vascular injuries in 18%, and transient neurologic deficits in 36% of our patients. Clinical pseudoarthroses developed in two patients, and tumor progression produced late instability in two patients with renal carcinoma. Thecal compression and late collapse led to therapeutic failure in four patients in 12-18 months. Fixation failure occurred in four patients, resulting from loosening of the plate on the screws in three patients, and breakage of a screw in one. Failure to adequately address anterior column disease was the primary cause of treatment failure in these patients. Proper seating of the plate on the pedicle screws is, likewise, crucial to construct stability and longevity. VSP instrumentation provides rigid fixation and allows more extensive tumor resection than traditional systems, while sparing vertebral motion segments. However, failure to address key technical and biomechanical principles may lead to serious complications.
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PMID:VSP stabilization of lumbar neoplasms: technical considerations and complications. 180 66

The SV40 T antigen (T)/adenovirus E1A-binding domain of the retinoblastoma gene product (pRB) has been fused to S. japonicum glutathione S-transferase, and the chimera, bound to insoluble glutathione, was used to search for cellular proteins that can interact specifically with pRB. At least seven such proteins were detected in extracts of multiple human tumor cell lines. These proteins failed to bind to a family of pRB fusion proteins that harbor inactivating mutations in the T/E1A-binding domain and to the wild-type fusion protein in the presence of a peptide replica of the pRB-binding domain of T. Therefore, the binding of one or more of these proteins may contribute to the growth-suppressing function of pRB.
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PMID:Identification of cellular proteins that can interact specifically with the T/E1A-binding region of the retinoblastoma gene product. 182 28

Melanosis was found to various extents in a wide array of tissues of all 23 autopsied mice whose transgene consisted of the tyrosinase promoter fused to the simian virus 40 early-region oncogenic sequences. Pigmentation in a given animal was attributable to any or all of the following; an increase in numbers of some normally pigmented cells of neural crest origin (a result compatible with early stages of transformation); elicitation of melanin synthesis in some cells that normally have little melanin, or none at all (the latter possibly signaling metaplasia); unusual intercellular transfer of pigment granules from melanocytes into certain normally unpigmented epithelia and endothelia; and profusion of melanin-phagocytizing cells. Neoplasms, occasionally also containing melanin, arose in association with some of these melanotic tissues and included three choroid plexus tumors, three endocardial tumors, two peripheral nerve sheath tumors (schwannomas), two cochlear tumors, two pineal gland tumors, one salivary gland tumor, and one nasal mucosa tumor. These apparently originated independently of the ocular and cutaneous melanomas found in the same animals. The events involved in melanosis may thus contribute to neoplastic conversion.
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PMID:Melanosis and associated tumors in transgenic mice. 184 37

IL6-PE40 and IL6-PE664Glu are chimeric molecules composed of interleukin 6 (IL6) fused to a truncated form (PE40) or a full-length mutated form (PE664Glu) of Pseudomonas exotoxin. Both forms of IL6-Pseudomonas exotoxin are cytotoxic to IL6 receptor-bearing tumor cell types in culture. In this report, we show that both IL6-PE40 and IL6-PE664Glu have antitumor activity against the hepatocellular carcinoma PLC/PRF/5 implanted s.c. in nude mice. The PLC/PRF/5 tumor contains about 2300 IL6 receptors per cell. IL6-PE664Glu showed improved therapeutic efficacy when released continuously for 7 days by an osmotic pump planted i.p. than when administered by multiple daily i.p. injections. Both forms of IL6 toxin exhibited a schedule-dependent antitumor effect. These results demonstrate that IL6-Pseudomonas exotoxin can suppress the growth of cancer which overexpresses cell surface IL6 receptors.
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PMID:Antitumor effects of interleukin 6-Pseudomonas exotoxin chimeric molecules against the human hepatocellular carcinoma, PLC/PRF/5 in mice. 185 60

Monoclonal antibodies which bind selectively to cancer cells are currently used for tumor localization and for targeting cytotoxic reagents. The success of these approaches depends on the specificity of the antibody and its reactivity to a majority of the tumor samples. Frequently, monoclonal antibodies are generated by immunizing mice with antigenic preparations from a single tumor cell line. Antibodies generated under these conditions often react to a narrow range of tumors. In the present study, mice were immunized with multiple ovarian cancer cell lines in a sequential manner to amplify the immune response against common antigenic determinants expressed in these cell lines. Spleen cells from the immunized mice were then fused with NS-1 myeloma cells to establish hybridomas. Two cell lines were selected on the basis of their selective reactivity to ovarian cancer cells after extensive screening. Monoclonal antibodies OVX1 and OVX2 bound to all 5 ovarian carcinoma cell lines tested and did not bind to normal fibroblast cells. These antibodies recognized a unique antigenic determinant present in ovarian and breast cancer cells. Cross-blocking studies showed that the binding of OVX1 and OVX2 is not displaceable by 10 other previously described anti-ovarian antibodies including OC125. In immunocytochemical studies, OVX1 reacted to a majority of ovarian cancer tissues (17 of 20) and did not bind to normal ovarian tissues. Preliminary results indicate that OVX1 and OVX2 antibodies are directed to a high molecular weight antigen. These antibodies could be used in the preparation of cytotoxic conjugates.
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PMID:Development of two new monoclonal antibodies reactive to a surface antigen present on human ovarian epithelial cancer cells. 185 17

With the objective of developing human T-T cell hybrids producing B-cell growth factor, we fused concanavalin A-activated T lymphocytes with cells of the Jurkat T cell line. The hybrids were selected on the basis of their ability to form colonies in soft agar, whereas the parent Jurkat T cell line did not. T-T cell hybrids were HLA-typed, screened by functional tests, and recloned by limiting dilution. In addition to obtaining B-cell growth factor-producing hybrids, we also obtained certain other T-T cell hybrids (as determined by HLA-typing) producing suppressor factors inhibiting proliferative responses and antibody production by human lymphocytes. Subsequently, a suppressor factor with similar inhibitory properties was identified in supernatants of the Jurkat T cell line. However, the Jurkat factor exhibited different biochemical and functional properties than the hybridoma-derived suppressor factors. Using two-parameter cell cycle analysis and the metachromatic fluorochrome acridine orange, we found that the hybridoma-derived 160 and 169 suppressor factors arrested phytohemagglutinin-induced proliferative of peripheral blood mononuclear cells in the G0/G1 phase of the cell cycle, whereas the Jurkat suppressor factor arrested proliferation in the S phase. Incubation of peripheral blood mononuclear cells with the 160, 169, or Jurkat suppressor factors for 24 hr at 37 degrees C, followed by washing, did not alter their cell cycle progression (or RNA content) in response to stimulation with phytohemagglutinin. The hybridoma-derived 160 and 169 suppressor factors and the Jurkat factor inhibited the growth but not the viability of cells from the following human tumor cell lines: A673 sarcoma cell line, SK-LC-6 and SK-LC-14 lung cell lines, SB, Raji, and Daudi lymphoblastoid cell lines, and FARR malignant melanoma cell line. In contrast, it did not affect the growth of murine L1210 cells and FS-4 normal human diploid fibroblasts. The hybridoma-derived 160 suppressor factor was selected to investigate its effect on cell-mediated cytotoxicity. The 160 suppressor factor did not inhibit natural killer cytotoxicity or its augmentation by interferon alpha or interleukin 2 or the generation of lymphokine-activated killer cells. However, this factor partially inhibited the generation of specific T cell-mediated cytotoxicity.
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PMID:Hybridoma-derived human suppressor factors: inhibition of growth of tumor cell lines and effect on cytotoxic cells. 187 5

DAB486IL-2 is a genetically engineered fusion protein consisting of a portion of diphtheria toxin fused to human IL-2. It is specifically cytotoxic for tumor cells which bear high-affinity IL-2 receptors (IL-2R). DAB389IL-2 is a similarly constructed hybrid protein which is smaller than DAB486IL-2 and is slightly more potent in vitro. We have developed a murine model of IL-2R-expressing malignancy to study the in vivo efficacy of these genetically engineered cytotoxins. Following intravenous administration of CP3 cells, C57BL/6 mice develop tumors which are lymphatic in distribution. When mice are injected i.v. with 10(6) CP3 cells, 90% of the animals show signs of observable tumor by day 10 to 20; death occurs in 50% of untreated animals by day 30. Intravenous treatment of mice with DAB486IL-2 (10 micrograms daily for 10 days), beginning 24 hr after administration of CP3 cells, increases mean survival time by approximately 50%. In comparative studies, DAB389IL-2 is more potent in vivo than DAB486IL-2, with approximately 90% of treated animals with no evidence of tumor at 60 days. The mechanism of action of tumor inhibition by DAB486IL-2 is specific, since treatment of animals which have IL-2R-negative EL4 tumors has not resulted in increased survival time. In addition, treatment of such tumors with DAglu53B486IL-2, a fusion protein which can bind to the IL-2R but is incapable of inhibiting protein synthesis, is ineffective.
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PMID:Impact of interleukin-2-receptor-targeted cytotoxins on a unique model of murine interleukin-2-receptor-expressing malignancy. 187 77


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