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

In vitro cell-mediated cytotoxicity (CMC) for [3H]proline-labeled target cells was demonstrated with the use of unfractionated populations of regional lymph node, spleen, and peritoneal cells (RLNC's, SPC's, PC's, respectively) from C57BL/6 and strain A mice. Syngeneic and allogeneic hosts were immunized sc or ip with C1300 tumor or syngeneic SPC's. The syngeneic and allogeneic host effector lymphoid cells showed various degrees of cytotoxicity for C1300 target cells 3-9 days after one immunization with C1300, whereas the effector lymphoid cells of hosts immunized with syngeneic SPC's generally showed less CMC for C1300 and frequently increased the growth of C1300 target cells when compared to C1300 targets plus media controls. Effector cells obtained from lymphoid organs in the region nearest the immunization (i.e., RLNC from sc-inoculated hosts) demonstrated significantly more CMC than did effector cells from more remote lymphoid organs. The PC's and SPC's of C1300 ip hyperimmunized allogeneic hosts produced greater CMC than did those of mice immunized once. This was not observed if syngeneic C1300 or SPC's were used as hyperimmunizing antigens. The CMC of nonimmunized host effector lymphoid cells for syngeneic labeled target cells was demonstrated.
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PMID:Immune responses to mouse neuroblastoma C1300. I. Preliminary observations on cell-mediated immune responses. 90 96

The effect of cis-DDP (cis-diamminedichloroplatinum(II)), trans-DDP (trans-diamminedichloroplatinum(II)), SPC (spermine-platinum(II) complex), and K2PtCl4 on the ribomononucleotide and RNA metabolism was studied. When Ehrlich ascites tumor cells were preincubated with the aforementioned compounds and then labeled with [C14]uridine a clear-cut suppression of the radioactive labeling of RNA was observed. As radioactivity incorporated into the pool of the free uridine nucleotides in the cells treated with platinum compounds was even higher in comparison with that of the non-treated cells a conclusion may be drawn with certainty that the platinum compounds studied inhibit RNA biosynthesis. It was also found that under the effect of these compounds in the in vivo-assessed rate of the conversion of uridine nucleotides into cytidine nucleotides was considerably diminished. Using NaH14CO3 as a radioactive precursor it was shown that platinum compounds also inhibited purine biosynthesis de novo, in particular the conversion of IMP into GMP and AMP. The pronounced inhibitory effect of the platinum compounds on essential steps of the pyrimidine and purine biosynthesis de novo may be at least partly responsible for the firmly established inhibition in the present study of RNA biosynthesis by platinum compounds. The inhibition of the synthesis of the mononucleotides and RNA by the platinum compounds may be closely related to their cytostatic and cytotoxic activities.
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PMID:The effect of some platinum compounds on the biosynthesis of RNA and its precursors. 170 15

The present work investigates the effect of cis-DDP (DDP, diamminedichloroplatinum(II)), trans-DDP, SPC (spermine platinum(II) complex), and K2PtCl4 on the activity of the CTP synthetase in the cytosol of Ehrlich ascites tumor cells. To study their in vitro effect, the platinum compounds were supplemented to the incubation mixture for the enzyme assay. A concentration dependent inhibition of the CTP synthetase was found which was strongest in the case of trans-DDP. When ascites cells collected from mice, pretreated in vivo with platinum compounds, were used, the enzyme assay showed that the inhibition is strongest in the case of cis-DDP and K2PtCl4 (about 90% inhibition). This distinct inhibitory effect of the platinum compounds in the present experiments may be explained with the metabolic conversions of the compounds in the organism to their more active forms and/or with the inhibition of the protein biosynthesis under their influence because the lifetime of the CTP synthetase is short. This last assertion is proved in this work by control experiments with the antibiotic cycloheximide, which is an inhibitor of the protein biosynthesis.
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PMID:The effect of some platinum compounds on the activity of the CTP synthetase of Ehrlich ascites tumor cells: in vitro and in vivo studies. 177 27

Recently Ge et al reported LAC-122, LAC-210 and LAC-163 McAbs against Human non-small cell lung cancer and LSC McAbs against human lung small cell carcinoma. The immunotoxin, composed of McAb LAC-122 conjugated with Ricin A chain has been reported to have the significant cytotoxic effect in vitro on lung adenocarcinoma cell line SPC-A-1 by Tan et al. The LAC-122 alone has no effect on this target cell in the presence of complement from human, rabbit or guinea pig. The tumor associated antigens of human lung cancer have been recognized for many years, but only few reports deal with the common antigens or common epitopes of the lung cancer. From one fusion, 20 hybrids had been observed, all of these culture supernatants could react with target cell by IF. One of them after 4 th cloning, immunoglobulin isotype of the monoclonal antibody thus far obtained belonged to IgM and named to LC-1. Table 1 showed the results of ABC staining of LC-1 with a variety of tumors, normal adult and fetal tissues. From 12 non-small cell lung cancers, including 7 lung adenocarcinoma, 2 lung squamous carcinoma, 3 lung giant cell carcinoma, only one adenocarcinoma gave negative staining. As for 6 small cell lung cancers, all of them showed the positive reaction. It could be also reacted with 11 other tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[McAb LC-1 against human lung cancer]. 255 85

Tumor growth is dependent upon angiogenesis. There is an intense search for pharmacological inhibitors of angiogenesis as a novel approach to treat angiogenic diseases, e.g., arthritis, diabetic retinopathy or cancer. A series of compounds, originally studied as potential protein kinase C inhibitors, included the diaminoanthraquinone NSC 639366 (1-[[3-(diethylamino)-2-hydroxypropyl]amino]-4-[(2,3- epoxypropyl)amino]-9,10-anthracenedione fumaric acid salt) (SPC-100097), was found to reversibly inhibit bovine endothelial cell growth with an IC50 that ranged between 1 and 4 nM. NSC 639366 reversibly inhibited endothelial cell migration, particularly endothelial cells stimulated by the potent angiogenic molecule, basic fibroblast growth factor. The activity of secreted urokinase-type plasminogen activator and active interstitial collagenase, but not gelatinase, was inhibited by NSC 639366. In vivo, angiogenesis was significantly inhibited by NSC 639366 by using the chick chorioallantoic membrane or the rat corneal bioassay. Two analogs of NSC 639366 did not inhibit endothelial cell growth. These experiments introduce a novel compound that could be clinically useful against angiogenic diseases and encourage further development of compounds that inhibit the plasminogen-plasmin system known to be a key regulator of angiogenesis.
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PMID:A diaminoantraquinone inhibitor of angiogenesis. 752 34

Using flow cytometry the authors analysed the effect of 24 Chinese medicinal herbs (CMH) in compound recipe on proliferation index (PI), DNA index, protein index and ratio of various phases in cell cycle of human lung adenocarcinoma cell (SPC-A-1), The PI were more than 20%, in 4 CMH, while 3 CMH such as Gynostemma pentaphyllum, Glehnia littoralis, Panax Ginseng, could strengthen the body resistance. That suggested using CMH of strengthening body resistance not only served as conventional tonice but also as tumor cell inhibitor. Meanwhile the action point of 24 CMH on cell cycle were different. Therefore according to these results a new recombined Chinese recipe would be more effectively used for clinical practice.
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PMID:[Effects of 24 Chinese medicinal herbs on nucleic acid, protein and cell cycle of human lung adenocarcinoma cell]. 764 28

We examined the effects of the synthetic matrix metalloproteinase inhibitor batimastat (BB-94) on lung colonization and spontaneous metastasis of a rat mammary carcinoma, HOSP.1P. This tumor expresses both latent and active forms of the matrix metalloproteinases MMP-2 and MMP-9, although the former, as in human breast cancer, is the most prominent. Administration of batimastat (6 x 30 mg/kg i.p.) inhibited by up to 80% both the number and median weights of HOSP.1P lung colonies following i.v. inoculation of cells. This implies an effect both on seeding efficiency and subsequent tumor development. In spontaneous metastasis assays, limited treatment with batimastat (commencing when s.c. tumors were established and continuing until 5 or 14 days after their surgical removal) significantly inhibited lung metastasis but had little effect on lymphatic metastasis. However, when treatment was initiated 2 days prior to surgery and continued until day 70, 100% of animals survived to day 120 when there was no evidence of metastatic disease. All control animals (n = 25) in two separate experiments died before day 100 with lymphatic, lung, and extrapulmonary metastases. Taken together, these data suggest that lymphatic dissemination by HOSP.1P tumor cells is less susceptible to inhibition by batimastat than vascular invasion, but that long-term treatment can effectively prevent the outgrowth of putative micrometastases in both lymph nodes and lungs, allowing sustained tumor-free survival.
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PMID:Control of lymphatic and hematogenous metastasis of a rat mammary carcinoma by the matrix metalloproteinase inhibitor batimastat (BB-94). 866 19

The schizont stage of the protozoan parasite Theileria parva induces features characteristic of tumor cells in infected bovine T-cell lines. Most strikingly T. parva-infected cell lines acquire unlimited growth potential in vitro. Their proliferative state is entirely dependent on the presence of a viable parasite within the host cell cytoplasm. It has been postulated that parasite proteins either secreted into the host cell or expressed on the parasite surface membrane are involved in the parasite-host cell interaction. We used an in vitro transcription-translation-membrane translocation system to identify T. parva-derived cDNA clones encoding secretory or membrane proteins. Within 600 clones we found one encoding a 17-kDa protein which is processed by microsomal membranes to a 14-kDa protein (11E), presumably by signal peptidase. The processed form is expressed in the T-cell line TpM803 harboring viable parasites. By immunolocalization we show that the 11E protein mostly resides within the parasite, often in close vicinity to membranous structures, but in addition it appears at the surface membrane. Amino acid sequence comparison suggests that 11E belongs to the glutaredoxin family, but is unique so far in containing a signal sequence for endoplasmic reticulum membrane translocation.
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PMID:Characterization of a secretory type Theileria parva glutaredoxin homologue identified by novel screening procedure. 900 54

Antigenic modulation of tumor cells is a kind of immunophenomenon that the antigenicity of tumor cell surface antigen could be lessened, weakened or completely lost. It is a potential route for tumor cells to escape the immunosurveillance and immunoattack of the host. One of the means to cause the antigenic modulation is by means of the antibody. In present research, gold labeled monoclonal antibody LC-1, which is raised against human lung cancer in our lab, as a molecular tracer to study the internalization and the subsequent fate of the membrane tumor associated antigen-LC-1 complex on the SPC-A-1 cell surface has been used. We found that this complex was internalized via the receptor-mediated endocytic pathway and concentrated in the multivesicular bodies and transported to lysosomes for proteolysis in the end. Strikingly, we noted that LC-1 had induced the autophagocytosis of ribosomes in SPC-A-1 cells in the median time it induced the internalization of the cell surface antigen cause by internalization and the restoration after antigenic modulation were also analyzed by the fluorescence activated cell sorter (FACS).
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PMID:[Internalization of tumor associated antigen on human lung adenocarcinoma cell line SPC-A-1 by McAb LC-1]. 963 8

The purpose of this study is to investigate how the insulin-like growth factor I receptor (IGF-IR) affects cellular radiosensitivity when cells are cultured under different growth conditions. For this, A7(R) and A7(puro) cells were established from human glioblastoma GB A7 cells. The former were derived from the parent cells by stable cotransfection with plasmids carrying human IGF-IR cDNA and a puromycin resistance gene and the latter had the marker gene alone. The cells were either grown exponentially in monolayer cultures or grown in multicellular spheroids as an in vitro model for solid tumors. Spheroids were formed in the two different methods, liquid-overlay (LOC) and spinner (SPC) cultures. Although the growth rate of both cell lines in monolayer was exactly the same, the growth rate of A7(R) spheroids formed in LOC was higher than that of A7(puro) spheroids. A central necrosis region was histologically observed in A7(puro) spheroids, but the corresponding region in A7(R) spheroids was almost completely filled with intact cells in both LOC and SPC spheroids. Both cell lines showed the same radiosensitivity in monolayer cultures in terms of cell viability and clonogenic cell survival. When the spheroids formed in LOC were X-irradiated, the radiosensitivity of A7(R) and A7(puro) cells assayed for cellular clonogenicity was also the same. However, in the spheroids formed in SPC, A7(R) cells were significantly more radiosensitive than A7(puro) cells. The results indicate that overexpression of the IGF-IR could induce radiosensitization of human tumor cells in spheroids while inhibiting spontaneous necrosis formation. This may open a possibility to explore the novel function of the IGF-IR.
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PMID:Differential effects of the insulin-like growth factor I receptor on radiosensitivity and spontaneous necrosis formation of human glioblastoma cells grown in multicellular spheroids. 1038 24


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