Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evaluation of double-stranded RNA by flow cytometric analysis is an important parameter for discriminating quantitatively between human tumoral and normal cells. We studied double-stranded RNA (ds-RNA) measurements using propidium-iodide after DNase treatment in bone marrow and in peripheral blood cells from patients with acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia and multiple myeloma. The highest incidence of ds-RNA excess (greater than 30%) was observed in patients with acute leukemia (75%), while those displaying it in complete remission phase were 20-25% and in relapse about 80%. A high incidence was also noted in patients with chronic myeloid leukemia in blastic crisis (100%) and in patients with multiple myeloma with heavy tumor stage myeloma (78%). We never observed an elevated ds-RNA excess in the control group, formed by normal peripheral blood lymphocytes. Indeed the specificity of this tumor marker is attested to not only by its high levels in various hematologic malignancies, but also by its absence in normal cells. Hence the importance of its clinical implications in malignant hematologic diseases is confirmed.
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PMID:Double-stranded RNA excess in hematologic diseases: clinical implications. 263 84

A new cytotoxic acridine alkaloid that exhibited antitumor activity in vivo was isolated from a marine Dercitus species sponge collected at a depth of 160 m in the Bahamas. This violet alkaloid, designated dercitin, inhibited the proliferation of cultured murine and human leukemia, lung, and colon tumor cells at nM concentrations (IC50 values of 63-150 nM) and prolonged the life of mice bearing ascitic P388 tumors (%T/C = 170, 5 mg/kg, i.p., QD1-9). Dercitin was also active against i.p. B16 melanoma and modestly inhibited the growth of s.c. Lewis lung carcinoma on the same schedule. DNA blocked the antiproliferative effects of the agent in culture, and incorporation studies indicated that dercitin disrupted DNA and RNA synthesis with less effects on protein synthesis, similar to the effects of known DNA intercalators. After 1-h exposure to 400 nM dercitin, the rates of incorporation of [3H]uridine, [3H]thymidine, and [3H]leucine by cultured P388 cells were inhibited 83, 61, and 23%, respectively. Equilibrium dialysis indicated that dercitin bound calf thymus DNA with an affinity of 3.1 microM and maximal binding of 0.20 mol dercitin/mol base pair. Binding involved intercalation as evidenced by ability to relax supercoiled phi X174 DNA (half maximal concentration for dercitin relaxation was 36 nM). The effects of dercitin on DNA mobility were reversible, and complete relaxation of DNA with topoisomerase I in the presence of dercitin followed by phenol extraction resulted in the appearance of supercoiled DNA. Dercitin, at microM concentrations, had a small effect in the K+-sodium dodecyl sulfate assay using cultured P388 cells, suggesting minimal inhibition of topoisomerase activity. But, dercitin completely inhibited DNA polymerase I/DNase nick translation of DNA at 1 microM. Relaxation of DNA at a given concentration was greater than inhibition of nick translation suggesting that the effects of dercitin on enzyme activity were secondary to changes in DNA conformation. Results indicate that dercitin is a new marine natural product that probably exerts its biological effects through intercalation into nucleic acids.
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PMID:Antitumor activity and nucleic acid binding properties of dercitin, a new acridine alkaloid isolated from a marine Dercitus species sponge. 254 17

We describe a method for establishing the culture of bovine tracheal submucosal gland (BTG) cells, in which we have also examined the influence of a reconstituted basement membrane matrix derived from the Engelbreth-Holm-Swarm tumor (EHS) on the growth and morphological differentiation of these cells. BTG cells have been isolated by tissue enzymatic digestion using trypsin, deoxyribonuclease I, elastase, hyaluronidase and EGTA for 1 hr at 37 degrees C. Afterwards, cells and tissue were collected by centrifugation and were incubated for 15 min with 15% newborn calf serum to inactivate the proteolytic enzymes. Enzymatic digestion using only trypsin, centrifugation and inactivation steps were repeated three times. Using this protocol, we obtained 15 +/- 4 (X 10(6] cells per g of tracheal submucosa with 72 +/- 2% (n = 5) cell viability. On microscopic observation, isolated cells were mainly composed of serous type glandular cells. Cells were cultured in a 1:1 medium of Dulbecco's Modified Eagle's/Ham's F12 supplemented with 10% fetal calf serum and subcultured in either plastic flasks or flasks coated with EHS matrix. On the plastic, the BTG cells exhibited at confluency an epithelioid appearance. They stained positively with the immunofluorescent anticytokeratin antibody and contained PAS-staining granules. By electron microscopy, lactoferrin, a protein marker specific to the serous cells, was demonstrated immunocytochemically in small secretory vesicles. BTG cells cultured on EHS matrix revealed a significantly increased growth in comparison to those cultured on plastic. In post-confluent culture of BTG cells on EHS matrix, we observed numerous dome-like structures formed by differentiated cells which were joined together around luminal spaces.
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PMID:Growth and characterization of isolated bovine tracheal gland cells in culture. Influence of a reconstituted basement membrane matrix. 260 69

Monoclonal antibodies (mAB) against progesterone receptor (PR) and the peroxidase-antiperoxidase (PAP) method to visualize PR in paraffin sections from 68 human breast cancers were used. Ten mAB, which recognize human PR on frozen sections, were tested. Six could detect PR in paraffin sections, with Li 417, LET 456, and LET 126 giving the best results. LET 126 antibody was used for most further studies. The effects of fixation with picric acid-formaldehyde (PAF), buffered-formalin, or with Bouin solution were investigated; all fixation methods allowed PR immunolabeling, although PAF or buffered formalin usually gave the best results. Positive staining was seen in the nucleus of carcinoma cells. Variations in intensity and extent of immunoreactivity were observed in all sections and among different regions of the same specimen. These were probably related to the heterogeneity of the tumor cell population. Results were compared with the PR content in the respective tumor tissues, determined by steroid-binding assay, and with immunocytochemistry on frozen sections. It was shown that there were correlations between the immunocytochemical staining (positive or negative) and the steroid binding assay (80%) and between the immunocytochemical staining on paraffin sections and on frozen sections (78%). Weaker intensity and fewer number of PR-positive cells were found for paraffin-embedded tumors. Estrogen receptors were also detected on adjacent sections from the same paraffin-embedded tissues by use of monoclonal anti-ER antibodies (ERICA-kit[Abbott Laboratories, Chicago, IL]) and DNase pretreatment. In conclusion, this immunocytochemical method for detection of PR and ER on paraffin sections offers an alternative to frozen tissue. It allows histologic and immunocytochemical studies on the same sample and retrospective studies on stored tissue blocks.
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PMID:Immunocytochemical staining of progesterone receptor in paraffin sections of human breast cancers. 267 23

Serum alkaline DNase activity (SADA) was investigated in rats receiving s.c. transplants of tumor cells sensitive or resistant to chemotherapy. Serum samples from each animal were collected before transplantation, during the development of tumors and after therapy. Within a few days after transplantation of both tumor lines (sensitive or resistant), SADA levels decreased progressively to 52% of the normal pre-transplantation level (p less than 0.01). This decrease in SADA preceded by 4 to 5 days the appearance of any palpable tumor mass. In all untreated animals as well as in treated rats bearing resistant tumors, SADA remained at a low level until death. In rats bearing tumors sensitive to therapy a progressive increase in SADA was observed after treatment, paralleling tumor regression. When tumor regression was complete, SADA resumed the levels of activity measured prior to transplantation.
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PMID:Variations in serum alkaline DNase activity in rats during growth and treatment of tumors sensitive or resistant to therapy. 271

The preferential colonization of a distant organ by a circulating tumor cell (organ specific metastasis) may be regulated by chemotactic factors present within the extracellular matrix of the host organ. Organ-specific extracellular matrix was prepared from murine kidney and lung by high salt extraction and DNAase/RNAase digestion. A soluble protein fraction (S2) from each of the matricies was obtained by 4 M guanidine extraction and was tested for organ-specific chemotactic activity in a modified Boyden chamber. The lung colonizing B16-F10 and B16-BL6 tumor cell lines demonstrated organ-specific motility only toward the lung extract. The low metastasizing B16 parental line and liver colonizing B16-L4b line showed no preference for either lung or kidney. The lung activity resolves into five fractions by gel filtration chromatography, with the highest activity eluting at Mr approximately 71,000. Chemotactic factors present in lung extracellular matrix may regulate the preferential colonization of an organ by stimulating the migration of tumor cells in a specific manner. These factors may be released during the degradation of the extracellular matrix.
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PMID:Organ-specific chemotactic factors present in lung extracellular matrix. 271 2

Mouse leukemia (P388) cells were incubated in cell culture medium containing nitrogen mustard [2-chloro-N-(2-chloroethyl)-N-methylethanamine] for 4 h. The nucleophosmin immunoband with a molecular weight of 37,000 (p37; other molecular weights are similarly designated) was observed in both control and nitrogen mustard-treated cells. Three additional immunobands with molecular weights of 80,000 (p80), 120,000 (p120), and 230,000 (p230) were identified in the drug-treated cells. The same results were observed with melphalan, but were not detected when mitomycin C, cis-platinum, Adriamycin, or actinomycin D were used. Treatments with DNase and RNase did not alter the molecular weights of these immunobands. These results indicate that the cross-linked products of nucleophosmin were not linked to DNA or RNA. The pI of p80, p120, and p230 is 5.1, which is the same as that of nucleophosmin (p37). The iodinated tryptic peptide map of p80 is identical to that of nucleophosmin. This result indicates that p80 is a dimer cross-linked by nitrogen mustard. The p80 and p120 immunobands were observed in Novikoff hepatoma and in hypertrophic rat liver, but were not detected in normal liver under the same conditions. These results indicate that tumor or proliferating cells have hexameric nucleophosmins which can be cross-linked by nitrogen mustards.
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PMID:Cross-linkage of nucleophosmin in tumor cells by nitrogen mustard. 272 Jun 80

Human hereditary diseases such as xeroderma pigmentosum, Fanconi's anemia, ataxia telangiectasia, and Bloom's syndrome are characterized by a proneness for developing cancer associated with abnormalities in the processing of DNA damage. The molecular defects responsible for predisposing human tissues to cancer are still not well understood, despite the fact that a considerable amount of work has already been done on this problem. In this paper, we show that in human tumor cell lines, in cells transformed by DNA tumor viruses, and in cells derived from certain cancer-prone disorders, the level of activity of a 42-kDa deoxyribonuclease is many times higher than in diploid untransformed control cells. This suggests that this activity is linked to, or may play a role in, malignant transformation.
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PMID:Enhanced deoxyribonuclease activity in human transformed cells and in Bloom's syndrome cells. 280 19

Estrogen receptor (ER) status of breast carcinomas determines prognosis and treatment. Biochemical ER assays are expensive and time-consuming and require fresh tumor. Immunohistochemical ER was assessed in 68 breast carcinomas, by an automated method using routinely processed formalin-fixed paraffin-embedded tissues, and manually with the use of snap-frozen tissues with a monoclonal anti-ER and peroxidase-antiperoxidase technique. The paraffin sections were digested with DNase to enhance development of signal. Positive nuclear ER was obtained in 9 (13%) fixed tissues and 36 (53%) frozen tissues. The sensitivity, specificity, and predictive value of a positive test result, as compared with the biochemical assay, were 25%, 100%, and 100% for the paraffin section technique, and 89%, 88%, and 89% for the frozen sections. Although it is specific, lack of sensitivity, resulting from loss of ER with fixation and room temperature handling, renders this immunohistochemical technique unacceptable on fixed tissues. However, ER immunostain on frozen tissue is an acceptable alternative to biochemical assay.
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PMID:Automated immunohistochemical estrogen receptor in fixed embedded breast carcinomas. Comparison with manual immunohistochemistry on frozen tissues. 281 20

BK virus (BKV) is a human papovavirus which latently infects a majority of the world population. Reactivation of this virus is associated with acute hemorrhagic cystitis, and BKV DNA has been found in human tumor tissue. BKV is one of many highly homologous papovaviruses, including simian virus 40 and JC virus, which display distinct host and cell-type specificities, transformation potentials, and pathologies. These differences are thought to be determined, in part, by the noncoding regulatory region of each virus, which contains the origin of replication and regulatory elements for both early and late gene expression. We have used linker scan mutants to map functional elements of a truncated BKV early promoter and enhancer and have studied the stereospecific requirements of these elements. We have also identified protein-binding regions through DNase protection studies. Our results show that a minimum of four elements are necessary for efficient early transcription, at least three of which correspond to DNase-protected domains. These protein-binding elements map to the TATA box and two nuclear factor 1 consensus sequences, one located within the enhancer repeat unit and the other located to the late side of the enhancer. The sequence of the fourth element is similar to the transcription factor Sp1 consensus sequence. Additional DNase-protected sites are centered over AP-1 and Sp1 consensus sequences. Finally, we find that the functional elements of the BKV early promoter and enhancer lack strict stereospecific requirements for efficient transcription.
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PMID:Linker scan analysis of the early regulatory region of human papovavirus BK. 284 91


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