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

The present experiments were designed to investigate whether it might be possible to combine their therapeutic benefits of autologous BMT and allogeneic BMT following administration of T-lymphocyte depleted marrow allografts with additional immunotherapy following BMT. The tumor model used for investigating graft vs leukemia (GVL) effects was the murine B-cell leukemia (BCL1), a spontaneous, nonimmunogenic, highly lethal leukemia of BALB/c origin. Immunotherapy with high dose recombinant human interleukin-2 (IL2) (10(5) Cetus units x 3/day intraperitoneally (IP) for 5 days) produced significant anti-tumor effects in BCL1-bearing mice. BALB/c mice inoculated with 10(3) BCL1 leukemia cells received were treated on day -1 with cyclophosphamide 100 mg/kg and transplanted with normal syngenic BM cells on day 0. High-dose IL2 (100,000 Cetus Units x 3/day IP x 5 consecutive days) was initiated on day +1, +7, or +21 following BMT. Optimal time for administration of IL2 was noted at 3 weeks post-BMT with 90% of the mice surviving with no evidence of disease greater than 1 year. An experimental model designed to study GVL effects in a state of minimal residual disease following T-cell depleted allogeneic BMT indicated that mice receiving low dose of BCL1 challenge (10(4] were successfully treated by either IL2 (2 x 10(4) Cetus units x 2/day IP x 3 days), allogeneic spleen cells (10(6) on day +1, 10(7) on day +5 and 5 x 10(7) on day +9) alone and certainly following a combination of both.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:IL-2 activated cell-mediated immunotherapy: control of minimal residual disease in malignant disorders by allogeneic lymphocytes and IL-2. 239 Jun 44

The lymphocyte function-associated (LFA)-1 molecule is expressed on certain populations of macrophages that have an augmented capacity to capture tumor cells. Accordingly, we analyzed the role of LFA-1 in the establishment of such cell-cell interactions. F(ab')2 fragments of the M17/4, anti-LFA-1 monoclonal antibody (MAb) inhibited the interaction between activated macrophages and tumor cells by up to 80% in a dose-dependent manner. The anti-LFA-1 MAb reduced (between 55 to 79%) the number of P815, LSTRA, or EL-4 tumor cells bound to trypsin-sensitive structures on bacillus Calmette Guerin activated macrophages. The inhibition appeared selective, because a F(ab')2 fragment of anti-Mac-1 did not inhibit such binding. Inhibition of tumor cell capture could be observed as soon as 15 min after the onset of the cell-cell interaction between activated macrophages and tumor cells. Optimal inhibition occurred when both tumor targets and macrophages were precoated with the MAb. Although P815, LSTRA, EL-4, and BW5147 tumor cells all expressed LFA-1, only the first three but not BW5147 cells were bound by activated macrophages. Furthermore, endotoxin-pulsed macrophages elicited by thioglycollate broth expressed the LFA-1 antigen but did not exhibit selective tumor cell capture. Finally, anti-LFA-1 inhibited the development of weak into strong binding. Taken together, the results suggest that LFA-1 molecules can participate in the interaction between activated macrophages and neoplastic cells.
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PMID:Mechanisms of tumor cell capture by activated macrophages: evidence for involvement of lymphocyte function-associated (LFA)-1 antigen. 242 81

Mobilization of the capillary endothelium is one of the first events observed during angiogenesis, and the study of conditions that control or influence the mobilization of the endothelium in vitro has been assumed to offer information relevant to the understanding of angiogenesis in vivo. In vitro mobilization of the bovine capillary endothelium was substantially enhanced by addition of gangliosides to the culture medium. Optimal mobilization was obtained when the endothelium incorporated the gangliosides first and was then seeded on fibronectin anchored to collagen type I. Preincubation of the capillary endothelium with gangliosides, trisialoganglioside in particular, doubled the amount of fibronectin bound to the cells and enhanced the migration about 5-fold. 'Blockage' of ganglioside binding with cholera toxin or gamma-interferon substantially reduced migration. Rabbit corneas, treated in vivo with a variety of angiogenesis effectors to induce neovascularization, consistently showed an increase in sialic acid content just prior to the time the tissue would be penetrated by the capillaries. This finding was interpreted to indicate that an increment of the ganglioside content of the capillary endothelial cell membranes may play a determinant role in the mobilization of the capillary endothelium in vivo as shown here to take place in vitro. Since the formation of a tumor from a micrometastasis requires formation of new capillaries and highly metastasizing tumors very frequently have high levels of sialic acid on the cell surface, it is hypothesized that production and shedding of gangliosides from the surface of neoplastic cells may be a factor in promoting angiogenesis and metastatic growth.
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PMID:Interaction of gangliosides with fibronectin in the mobilization of capillary endothelium. Possible influence on the growth of metastasis. 242 14

Scrape loading and sonication loading are two recently described methods of introducing macromolecules into living cells. We have tested the efficacy of these methods for transfection of mammalian cells with exogenous DNA, using selection systems based either on resistance to the drug G418 (Geneticin) or on acquisition of the ability to utilize the salvage pathway of pyrimidine biosynthesis. These loading methods can be employed to generate cell lines that express the gene product of the transfected DNA molecules both transiently and stably. Optimal transfection is observed when the DNA is added to cells in physiological saline lacking divalent cations and containing K+ in place of Na+. DNA molecules 7.1 to 30 kilobases long have been introduced by the scrape loading procedure. In addition, the scrape loading procedure has been employed for cotransfection and subsequent expression of nonselectable genes encoded on DNA molecules added in a mixture with DNA molecules whose expression is selected. Cell lines expressing oncogenes or proteins that are important for regulation of cell growth and division have been obtained by this procedure. The scrape loading procedure is also useful for studies of the cellular changes that occur upon expression of an exogenous gene. As many as 80% of cells scrape loaded with the plasmid pC6, which encodes the simian virus 40 large tumor antigen, contained this protein in the nucleus between 1 and 5 days after transfection. Thus, scrape loading and sonication loading are simple, economical, and reproducible methods for introduction of DNA molecules into adherent and nonadherent cells, and these methods may be useful in the future for experimentation at both fundamental and applied levels.
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PMID:Transfection of mammalian cells with plasmid DNA by scrape loading and sonication loading. 244 24

Optimal conditions for the quantitation of free prolactin binding components of human prostatic tissue obtained by TURP were studied by applying gamma receptor assay. The radioligand used was 125I-prolactin. Significantly greater heat stability of the prostate membrane prolactin binding sites, when compared to that of androgen cytoplasmic receptors, was confirmed. The saturability and specificity of the prolactin binding components was demonstrated by the results of both Scatchard plot analysis and displacement studies. Free prolactin receptors were found in none of the poorly differentiated (G3) prostatic tumors examined, and only in 62.5% of medium differentiated (G2) prostatic malignancies. The majority of tissue specimens coming from patients with either BPH or well differentiated prostatic tumor (G1) contain measureable amounts of free prolactin membrane binding components. In the present study we report also the case in which the change in tumor differentiation toward a higher grade (G2 to G1, provoked by the successful chemohormonal treatment) is accompanied with the appearance of previously absent free prolactin binding components. In histologically proven BPH tissue specimens free prolactin receptor negative status has been found in most patients with a slight increase in serum PAP values, while receptor rich status was detected in the majority of those with elevated PSA concentrations. We believe therefore that the prolactin receptor values, when used as part of the multivariable analysis, may participate in further delineation of the role of prolactin in the development of prostate cancer, but may also play a role in a subclinical prediction related to the conversion of either an adenoma or a latent adenocarcinoma to the clinically manifest prostatic malignancy.
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PMID:Unoccupied prolactin binding components of the benign and malignant human prostate in a subclinical and clinical procedure. 247

Evidence indicates that activation of a beta 1----3N-acetylglucosaminyltransferase is responsible for accumulation of large quantities of lacto-series tumor-associated antigens in human colonic adenocarcinomas. Expression of type 1 and 2 core chain derivatives characterize human colonic adenocarcinomas, whereas normal adult colonic epithelial cells express detectable quantities of only type 1 chain derivatives. The basis for preferential synthesis of type 1 chain lacto-series carbohydrate structures characteristic of normal colonic mucosa and human colonic adenocarcinoma Colo 205 cells has been studied. The beta 1----3- and beta 1----4galactosyltransferase enzymes associated with synthesis of type 1 and 2 core chain structures, respectively, have been separated from a Triton X-100 solubilized membrane fraction of Colo 205 cells by chromatography on an alpha-lactalbumin-Sepharose column and their properties studied. Optimal transfer of beta 1----3-linked galactose to acceptor Lc3 occurred in the presence of 0.1% Triton CF-54 with Triton X-100 providing 75% of maximal activity. The enzyme was active over a broad pH range from 6.5 to 7.5 and had a near absolute requirement for Mn2+. The Km values for donor UDPgalactose and acceptor Lc3 were determined to be 48 and 13 microM, respectively. In contrast, the beta 1----4galactosyltransferase required taurodeoxycholate for maximal activity and the Km for Lc3 was found to be 20-fold higher than that for the beta 1----3-specific enzyme under the same assay conditions. Studies with membrane-bound beta 1----3- and beta 1----4galactosyltransferases as found in Golgi-rich membrane fractions of SW403 and Colo 205 adenocarcinoma cells showed that preferential synthesis of type 1 chain structures occurs under conditions similar to those in vivo for biosynthesis of lacto-series core chains. The results suggest that both the higher affinity of the beta 1----3galactosyltransferase for acceptor Lc3 and the membrane organizational features result in preferential synthesis of type 1 chain structures.
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PMID:Characterization and membrane organization of beta 1----3- and beta 1----4-galactosyltransferases from human colonic adenocarcinoma cell lines Colo 205 and SW403: basis for preferential synthesis of type 1 chain lacto-series carbohydrate structures. 249 70

Supernatants of IL-2-activated mononuclear cells (MNC) that displayed an optimal lymphokine-activated killer (LAK) cell activity at 48-72 hr in culture were found to contain increased levels of tumour necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha) and interferon-gamma (IFN-gamma) when compared with supernatants from mononuclear cells cultured in the absence of IL-2. The concentration of TNF alpha and IL-1 alpha produced by MNC at 24 hr was either increased or maintained by extending the cultures to 96 hr. In contrast, TNF beta was only detected at very low levels after 72-96 hr culture, irrespective of whether IL-2 was present or absent. Optimal concentrations of IL-2 needed to induce maximum release of TNF alpha, IL-1 alpha and IFN-gamma by MNC varied among different individuals. Enriched populations of lymphocytes secreted higher levels of all measured cytokines upon activation with IL-2 in contrast to untreated cells. Supernatants from purified monocyte preparations contained high concentrations of TNF alpha and IL-1 alpha regardless of the presence of IL-2 in the cell cultures. This work suggests that in addition to the generation of LAK cell activity, by promoting the release of other cytokines with potential anti-tumoricidal activity, IL-2 may be amplifying cell-mediated cytotoxicity, which is associated with protection against neoplastic disease.
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PMID:Release of cytokines during generation of lymphokine-activated killer (LAK) cells by IL-2. 251 40

The biological behavior of 111In-labeled HPD has been investigated in tumor-bearing animals. Mice mammary adenocarcinomas and 7,12-dimethylbenz(a)anthracine induced breast tumors in Sprague-Dawley female rats were clearly visualized by 111In-HPD nuclear scintigraphy. Optimal scans were obtained after a 48 h delay. In normal and tumor-bearing animals, the highest uptake of 111In-HPD 72 h post-injection was found in the liver, the spleen and the kidneys. Depending on the size and the extent of necrosis, the uptake of 111In-HPD by malignant breast tumors varied from 2.5% injected dose (ID) (range 0.14-5.3% ID) in mice to 1% (range 0.22-8.1% ID) in rats. Benign breast tumor uptake of 111In-HPD was less than 1% ID. No significant amount of the radiopharmaceutical was found in pulmonary abscesses and abdominal cysts (less than 0.1% ID). Scintigrams of these infectious or inflammatory lesions were normal. Malignant tumor to blood, heart and lung ratios averaged 50:1, 10:1 and 3:1 respectively. Tumor to brain ratio ranged from 72 to 444:1.
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PMID:In vivo assessment of 111In-labeled hematoporphyrin derivative in breast tumor-bearing animals. 252 78

Macrophage colony-stimulating factor (M-CSF) is known to stimulate proliferation of monocyte/macrophage progenitors and enhance in vitro antitumor cytotoxicity by murine macrophages. In this paper we have shown that recombinant human M-CSF causes human peripheral blood monocytes to differentiate in culture into metabolically active macrophage-like cells. These cells mediate very efficient antibody-dependent cellular cytotoxicity (ADCC) against human melanoma and neuroblastoma cell lines in the presence of two murine IgG3 mAbs (3F8 and R24). They also mediate antibody-independent cytotoxicity (or cytostasis) to a lesser extent. Human serum had an inconsistent effect on ADCC, but often induced similar high levels of ADCC. Cytotoxicity was measured using a novel ELISA to detect surviving tumor cells after ADCC. Two conventional isotope-release assays (51Cr and [3H]TdR) underestimated or entirely failed to detect ADCC by M-CSF-activated monocytes. Optimal activation occurred with 100-300 U/ml of M-CSF, and required 9-11 d for completion. Most of the M-CSF cultured monocytes expressed the low-affinity Fc receptor (CD16). ADCC by cells of the monocyte/macrophage lineage using murine IgG3 mAbs may have significance for the immunotherapy of human malignancies.
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PMID:Antibody-dependent antitumor cytotoxicity by human monocytes cultured with recombinant macrophage colony-stimulating factor. Induction of efficient antibody-mediated antitumor cytotoxicity not detected by isotope release assays. 252 48

Optimal conditions for the screening of cervical scrapes for human papillomavirus (HPV) were investigated by using filter in situ hybridization. Since integrated and episomal HPV can be found, cell lines containing viral DNA in an integrated form (HPV in CaSki) or in an episomal state (BK virus-induced hamster tumor cells) were used for optimization experiments. An increase in sensitivity was achieved by alkaline denaturation and neutralization before the specimens were spotted onto the membrane. This increase was 5-fold for the episomal virus and 16-fold for the integrated virus in the model system, as compared with other methods. To evaluate this method on clinical material, 1,963 cervical scrapes were screened for the presence of HPV 6/11 and HPV 16. Nineteen scrapes were positive for HPV 6/11 or HPV 16; and in 1,810 scrapes, no HPV 6/11 or HPV 16 could be detected by the modified filter in situ hybridization technique. Scrapes from which the interpretation of the modified filter in situ hybridization results were equivocal (n = 71, 3.6%) or in which positivity was detected for both HPV 6/11 and HPV 16 (n = 63, 3.2%) were further analyzed by the DNA dot spot technique. Eight scrapes with an equivocal result and only one scrape showing a double positivity by the modified filter in situ hybridization technique could be confirmed in the dot spot assay. In the total group 12 scrapes were positive for HPV 6/11 DNA, 15 were positive for HPV 16 DNA, and 1 was positive for both HPV 6/11 and HPV 16 DNA. Southern blot analysis on modified filter in situ hybridization-positive and -negative scrapes revealed a 100% correlation.
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PMID:Optimization of human papillomavirus genotype detection in cervical scrapes by a modified filter in situ hybridization test. 253 84


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