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

Murine breast cancer cell lines were developed to selectively invade the peritoneum while they proliferated in ascites form in the abdominal cavity. In a dominant form of invasion, tumor cells showed special affinity for elastin fibers and squeezed through narrow gaps in the elastic fiber meshwork of the stroma. Even in fixed tissue, such cells could be recognized as being in the process of invasive migration because of their dumbbell shape. This appearance was similar to that of diapedetic blood cells traversing bone marrow sinus endothelium. Three-dimensional STERECON graphics reconstruction from serial thick sections of 44 such cells was carried out. The reconstructions showed that, in mid-penetration, the cells spread extensively over the exterior surface of the elastic fiber meshwork. The cell surface contact of these forward projections was mainly with the elastic fiber outer coat of microfibrils, but small areas of the cell surface also fused directly to inner-core elastin. The morphological rearrangement of the cytoskeleton was minimal in both types of attachment areas. The location of these forward facing attachments is consistent with mechanisms for pulling the invasive cell through the gap. Lamellopodia formation and clustering of cytoplasmic organelles occurred more commonly at the forward-facing part of the cell. Morphometry of the reconstructions showed that a contraction of the whole cell occurred during the squeezing/migration process suggestive of an additional pushing process. However, our invasive cell lines showed marked differences in the degree of cell shrinkage. The process of adhesion and squeezing of tumor cells through elastin meshworks in vivo is clearly a complex phenomenon. Changes in cell surface activity appear to play a significant role in establishing the necessary 'foothold' component of invasion and, possibly, in the generation of tractive force as well.
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PMID:Organelle rearrangement and cell volume changes during squeezing invasion of peritoneal elastic lamina by targeted murine breast carcinoma cells. 188 32

To study the development of tissue and cell damage, the early morphologic changes induced by photodynamic therapy (PDT) with the new photosensitizer bacteriochlorin a (BCA) were investigated in Greene hamster melanoma implanted in the anterior eye chamber of white rabbits up to 24 hr after BCA-PDT, using light and electron microscopy. Immediately after BCA-PDT, intracellular spaces were enlarged, and blood vessels were clotted with swollen erythrocytes. By electron microscopy, it was found that some mitochondria had fused inner and outer membranes, and the cristae mitochondriales were affected. With time, the severity of the tissue and cell damage increased, leading to almost complete tumor necrosis after 24 hr. The direct mitochondrial damage and the vascular damage induced by BCA-PDT probably both contribute to tumor necrosis.
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PMID:Morphologic effects of bacteriochlorin a and light in vivo on intraocular melanoma. 189 68

We have investigated the in vivo function of a chimeric protein constructed by recombinant DNA techniques. The behavior and antitumor activity of a protein A-lymphotoxin chimera (ALT) was examined on a murine tumor in mice in comparison with amino-terminal 19 amino acid-deleted lymphotoxin (dLT). Seven-week-old male BALB/c mice were implanted intradermally with Meth-A fibrosarcoma on day 0. ALT and dLT caused tumor regression, hemorrhagic necrosis and complete regression in a dose-related way when each agent was given intratumorally 5 times (days 5-9). The ratio of the median effective doses for complete tumor regression was 1.6 between ALT and dLT on a molar basis. ALT caused tumor regression and body weight loss when given intravenously on the same schedule. Biodistribution studies with 125I-labeled ATL and dLT demonstrated that, after intratumoral administration, ALT was retained longer in the administered site and was cleared more slowly from the mouse body than dLT. These findings suggest that a protein A-lymphotoxin chimeric protein expresses both antitumor activity similar to that of lymphotoxin and characteristic in vivo behavior of the fused protein A portion.
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PMID:Preparation of recombinant protein A-lymphotoxin chimeric protein and its antitumor effects in mice. 190 Aug 26

The first consistent karyotypic abnormality found to be associated with neoplastic disease was the Philadelphia (Ph) chromosome (Nowell & Hungerford, 1960). Furthermore, the best-studied example of translocation-mediated gene activation occurs in leukaemia patients bearing this abnormality (reviewed by Kurzrock et al, 1988). In these individuals, the Ph translocation (t(9;22)(q34;q11)) results in transposition of the ABL proto-oncogene from chromosome 9q34 to 22q11, where it is fused with part of the BCR gene. It is now known that as a result of the Ph translocation, p160BCR and p145ABL (the normal BCR and ABL gene products) are replaced by p210BCR-ABL. This aberrant protein constitutes the molecular fingerprint of CML. The enhanced tyrosine phosphokinase enzymatic activity (a property possessed by some growth factor receptors and transformation-inducing oncogenes) of p210BCR-ABL implicates a direct role for this molecule in the pathogenesis of CML. Because the Ph translocation is present in the early chronic phase, the union of the BCR and ABL genes is probably involved in the initiation of the leukaemic process. The secondary molecular forces driving progression of CML to blast crisis are however unknown, and may differ from patient to patient. Approximately 10% of CML patients lack a Ph chromosome. One-half of these individuals have bcr rearrangement and express p210BCR-ABL. Ph+ and Ph- bcr+ (p210+) CML are identical and should be treated the same. Molecular follow-up of diploid bcr+ CML patients is essential for detection of persistent malignancy after therapy. The presence of a specific marker--the BCR-ABL message--permits the development of new diagnostic approaches for CML. For instance, detection of a BCR-ABL message with the use of the highly sensitive polymerase chain reaction, a technique capable of detecting up to one leukaemia cell amongst one million normal cells, yields important information about minimal residual disease. Finally, the use of therapy directed against the BCR-ABL product may be a worthwhile strategy which deserves investigation, and may prompt a new era of tumour-specific treatment.
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PMID:The molecular pathology of chronic myelogenous leukaemia. 193 6

Tumor-infiltrating lymphocytes were isolated from a primitive neuroectodermal tumor and fused with GM4672 cells, resulting in hybrids secreting human IgM-kappa antibody, which is reactive to olfactory neuroblastoma tumor cells. Hybridoma clones 4F and 9G produce human monoclonal antibodies reactive to autologous and allogeneic neuroblastoma tumor cells and subsets of pancreatic islet cells in formalin-fixed tissues. They react specifically with dense core granules of glucagon and insulin-producing islet cells, but not with those in cells producing somatostatin. Calcitonin granules are not recognized by these antibodies. The area of localization of the granules is distinct from the component labeled by murine monoclonal antibodies to chromogranin A. The clones have remained stable in culture for over two years and continue to secrete up to 60 micrograms/mL of human IgM. This study demonstrates the possibility of directly analyzing the antibody repertoire of tumor-infiltrating B cells, and this technique may allow the development of human monoclonal antibodies to other novel cellular antigens.
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PMID:Human monoclonal antibodies to neuroendocrine granules derived from tumor-infiltrating lymphocytes isolated from a primitive neuroectodermal tumor. 196 74

Five novel complementary DNA (cDNA) clones which are differentially expressed between two closely related T lymphoma cell clones were isolated using subtraction-enriched differential screening. SL12.4 cells, from which the cDNAs were isolated, have characteristics of thymocytes at an intermediate stage in development and cause prominent extranodal ovarian tumors in syngeneic animals. A sister cell clone, SL12.3, derived from the same tumor, has a distinct phenotype and causes more aggressive, diffuse lymphomas. Four of the five novel genes are expressed in normal thymus, activated spleen cells, or gut-associated lymphoid tissue. The DNA sequence and predicted protein sequence are presented for one of the novel cDNA clones. This novel cDNA clone detects mRNA in normal thymus, gut-associated lymphoid tissue, and ovarian tissue. The predicted protein has four putative transmembrane-spanning regions. The expression of the transcript is repressed in somatic cell hybrids formed from SL12.4 cells fused with three different T lymphoma cell lines which lack detectable mRNA complementary to the novel cDNA clone. This trans-negative regulation suggests that the expression of the gene is regulated by repressional mechanisms.
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PMID:Isolation of novel complementary DNA clones from T lymphoma cells: one encodes a putative multiple membrane-spanning protein. 198 Jun

Several ring-contracted analogues of the antitumor agent etoposide have been prepared. The synthesis of the simple indanyl system 3 is described along with two bicyclic systems of general structure 4 prepared through a stereoselective allylation of the keto-ester 6. A cis-fused lactone analogue 5, which is isomeric with the etoposide aglycone, has been synthesized via a dialkylation of the indene-2-carboxylate anion. Regiochemical and stereochemical results of these alkylations are described. The cytotoxicity of these derivatives toward several tumor cell lines is described and generally follows the structure-activity relationships known for the agent podophyllotoxin (2).
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PMID:Synthesis and antitumor activity of structural analogues of the epipodophyllotoxins. 200 77

A case of Klippel-Feil syndrome with crossed renal ectopia with fusion and unilateral vertebral artery occlusion is reported. A 61-year-old female was admitted because of having developed myelopathy, gait and sensory disturbance. The physical examination on admission revealed spastic gait and hypesthesia of the lower extremities. A hand size, elastic hard tumor mass was palpable at the right lower abdomen. The cervical radiogram showed fused 5th, 6th and 7th cervical vertebrae and severe spondylotic changes. Laminectomy was performed because of severe compressions of the cervical cord, evaluated by Metrizamide CT scans and MRI. The left subclavian angiogram showed occlusion of the left vertebral artery, and excretory pyelogram and abdominal CT scans showed crossed renal ectopia with fusion. 99mTc-DTPA renoscintigram revealed poor RI uptake and low glomerular filtering rate of ectopic kidney. The patients with Klippel-Feil syndrome are at greater risk of having a renal anomaly and a vascular accident of the vertebral artery. Examinations of urogenitary organs and vertebral arteries are necessary for the treatment of this syndrome.
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PMID:[A case of Klippel-Feil syndrome with crossed renal ectopia with fusion and unilateral vertebral artery occlusion]. 202 78

The Ph chromosome was the first specific karyotype abnormality associated with a particular neoplastic disease in humans. For many years it was suspected that chromosome abnormalities might cause cancer by alteration of specific genes or their expression. Significant recent developments in our understanding of the molecular consequences of the Ph translocation strengthen that assumption. The Ph translocation generates a hybrid gene consisting of 5' regulatory, promotor, and exon sequences of the bcr gene on chromosome 22 fused to 3' exons and polyadenylation/termination sequences of the ABL proto-oncogene from chromosome 9. It is well established that fusion of bcr and abl genes plays a crucial role in the pathogenesis of CML and ALL. Molecular methods can therefore be used as diagnostic tools to detect the Ph chromosome. Presently, the model of oncogenesis provided by our knowledge of how the abl proto-oncogene becomes activated as a result of the Ph translocation is one of the clearest models of oncogene activation. Despite the progress made, many areas remain to be explored. One important question is, how the hybrid protein is involved in leukemia. Research aimed at investigating the normal function of abl and bcr may be important in efforts to understand their abnormal functioning in leukemia and to increase our understanding of the disease.
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PMID:Molecular insights into the Philadelphia translocation. 205 Jun

Secreted phosphoprotein 1 (Spp-1) is a 41.5-kDa bone sialoprotein presumed to be important in the development and functioning of a number of mammalian organs and possibly also in the progression of malignancies. We report here the isolation of a phage lambda genomic clone of the murine Spp-1 gene containing the promoter and first six exons (4.6 kb of the 5.7-kb gene). We have found another exon located 5' to the 'exon 1' reported by Miyazaki et al. [J. Biol. Chem. 265 (1990) 14432-14438]. The DNA upstream from this 5' exon functions as a promoter in epidermal fibroblast and osteoblast-like cells, as demonstrated by transient transfection assays, S1 mapping of the transcription start point, and sequence analysis revealing TATA-like (TTTAAA) and CAAT (its inverse complement) boxes. A small region of the promoter (nt -253 to +79) was able to direct high-level expression of a fused cat reporter gene in JB6 mouse epidermal cells. The transient transfection assays indicated the presence of a positive transcription element between nt -543 and -253 and a negative transcription element between nt -777 and -543. Addition of the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), resulted in a 1.5-3-fold induction of transcription, depending on the promoter construct and the TPA concentration. The Spp-1 mRNA was localized in several tissues, consistent with previous reports, and to novel sites in ovary, and in the skin and ventral fatty tissue of pregnant and lactating mice. The induction of Spp-1 mRNA was partially mimicked by painting beta-estradiol or progesterone on the skin of nonpregnant females.
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PMID:The murine gene encoding secreted phosphoprotein 1 (osteopontin): promoter structure, activity, and induction in vivo by estrogen and progesterone. 205 67


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