Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bioluminescent imaging (BLI) permits sensitive in vivo detection and quantification of cells specifically engineered to emit visible light. Three stable human tumor cell lines engineered to express luciferase were assessed for their tumorigenicity in subcutaneous, intravenous and spontaneous metastasis models. Bioluminescent PC-3M-luc-C6 human prostate cancer cells were implanted subcutaneously into SCID-beige mice and were monitored for tumor growth and response to 5-FU and mitomycin C treatments. Progressive tumor development and inhibition/regression following drug treatment were observed and quantified in vivo using BLI. Imaging data correlated to standard external caliper measurements of tumor volume, but bioluminescent data permitted earlier detection of tumor growth. In a lung colonization model, bioluminescent A549-luc-C8 human lung cancer cells were injected intravenously and lung metastases were monitored in vivo by whole animal imaging. Anesthetized mice were imaged weekly allowing a temporal assessment of in vivo lung tumor growth. This longitudinal study design permitted an accurate, real-time evaluation of tumor burden in the same animals over time. End-point bioluminescence measured in vivo correlated to total lung weight at necropsy. For a spontaneous metastatic tumor model, bioluminescent HT-29-luc-D6 human colon cancer cells implanted subcutaneously produced metastases to lung and lymph nodes in SCID-beige mice. Both primary tumors and micrometastases were detected by BLI in vivo. Ex vivo imaging of excised lung lobes and lymph nodes confirmed the in vivo signals and indicated a slightly higher frequency of metastasis in some mice. Levels of bioluminescence from in vivo and ex vivo images corresponded to the frequency and size of metastatic lesions in lungs and lymph nodes as subsequently confirmed by histology. In summary, BLI provided rapid, non-invasive monitoring of tumor growth and regression in animals. Its application to traditional oncology animal models offers quantitative and sensitive analysis of tumor growth and metastasis. The ability to temporally assess tumor development and responses to drug therapies in vivo also improves upon current standard animal models that are based on single end point data.
 ...
PMID:Bioluminescent imaging (BLI) to improve and refine traditional murine models of tumor growth and metastasis. 1471 7

Inhibitory natural killer cell receptor (NKR)-expressing cells may induce a graft-versus-leukemia/tumor (GVL/T) effect against leukemic cells and tumor cells that have mismatched or decreased expression of HLA class I molecules and may not cause graft-versus-host disease (GVHD) against host cells that have normal expression of HLA class I molecules. In our study, we were able to expand inhibitory NKR (CD94/NKG2A)-expressing CD8+ T cells from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (G-PBMCs) by more than 500-fold using stimulation by an anti-CD3 monoclonal antibody with interleukin 15 (IL-15). These expanded and purified CD94-expressing cells attacked various malignant cell lines, including solid cancer cell lines, as well as the patients' leukemic cells but not autologous and allogeneic phytohemagglutinin (PHA) blasts in vitro. Also, these CD94-expressing cells prevented the growth of K562 leukemic cells and CW2 colon cancer cells in NOD/SCID mice in vivo. On the other hand, the CD94-expressing cells have low responsiveness to alloantigen in mixed lymphocyte culture (MLC) and have high transforming growth factor (TGF)-beta1- but low IL-2- producing capacity. Therefore, CD94-expressing cells with cytolytic activity against the recipient's leukemic and tumor cells without enhancement of alloresponse might be able to be expanded from donor G-PBMCs.
 ...
PMID:Cytolytic activity and regulatory functions of inhibitory NK cell receptor-expressing T cells expanded from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells. 1507 36

A novel intraluminal colon tumor model was established in mice by intrarectal instillation of colon cancer cells followed by short-term induction of colitis by an irritant agent. Male BALB/c mice were fed a diet containing 3% (w/w) dextran sulfate sodium (DSS) for 7 days to induce colitis, and colon 26 cells (1-2 x 10(6) cells/mouse) were infused intrarectally after the mice had been deprived of food for the last 18 h of DSS treatment. The tumor incidence (%) and size (mean volume +/- SD, mm(3)) at the rectal mucosa were 35% (2 +/- 3), 95% (96 +/- 79), 95% (141 +/- 137) and 94% (325 +/- 270) at 1, 2, 3 and 4 weeks after instillation of tumor cells, respectively. Histopathological analyses revealed that a solid tumor was formed initially at the rectal mucosa at 1 week after instillation, then became invasive into the submucosal and muscular tissues at 3 weeks after implantation. Intrarectal instillation of human colon cancer cells, LS174T (1 x 10(7) cells/mouse), mixed with "Matrigel" (0.5 mg/mouse), an extracellular matrix solution, in SCID mice led to formation of rectal tumors at 4 weeks after instillation, and immunohistochemical analysis revealed that the tumor cells expressed human carcinoembryonic antigen, suggesting that the tumor nodule was derived from the instilled LS174T cells. Oral or intravenous administration of a camptothecin (CPT) derivative, CPT-11, resulted in a significant reduction in tumor incidence and tumor volume in the colon 26-intraluminal implantation system. In conclusion, it was suggested that the present intraluminal colon tumor model is useful for examination of chemotherapeutic agents and also intraluminal factors (dietary compounds, intestinal microflora, etc.) that might function to suppress or enhance the growth of colorectal cancer in situ.
 ...
PMID:A novel mouse model of rectal cancer established by orthotopic implantation of colon cancer cells. 1518 33

Three human Escherichia coli heat-stable peptide (STh) analogues, each containing a DOTA chelating group, were synthesized by SPPS and oxidative refolding and compared in in vitro and in vivo systems. One analogue, DOTA-F19-STh(1-19), contains an N-terminal DOTA group attached via an amide bond linkage to an STh moiety which is essentially wild-type except for a Tyr to Phe alteration at position 19 of the molecule. A second analogue, DOTA-R1,4,F19-STh(1-19), differs from the first in that asparagine residues in positions 1 and 4 have been altered to arginine residues in order to examine the effect of positively charged groups in the linker domain. A third analogue, DOTA-11AUN-F19-STh(1-19), differs from the first in that it incorporates an 11-aminoundecanoic acid spacer group between the DOTA group and the first asparagine residue. In vitro competitive binding assays utilizing T-84 human colon cancer cells demonstrated that significant alterations to the N-terminal region of the STh molecule were well tolerated and did not significantly affect binding affinity of STh for the guanylyl cyclase C (GC-C) receptor. Internalization and efflux studies of the indium-labeled species demonstrated that inclusion of positive charge in the linker moiety inhibits internalization of the compound within tumor cells. The characteristics of the three analogues were compared in an in vivo model utilizing T-84 human colon cancer cell xenografts in SCID mice. Clearance of all analogues was rapid, primarily via renal excretion into the urine, with >89% ID excreted into the urine at 1 h pi for all analogues. The 111In-DOTA-R1,4,F19-STh(1-19) and 111In-DOTA-11AUN-F19-STh(1-19) analogues both had longer residence times in the blood than did the 111In-DOTA-F19-STh(1-19) analogue, probably accounting for increased %ID/g values for tumors and nontarget tissues at 1 h pi. At 4 h pi, significant differences between analogues were only seen with respect to metabolic routes of excretion, indicating that increased blood residence time did not result in increased tumor residualization. Reduction of hepatic uptake of these compounds, however, could have significance in the development of agents for the imaging of hepatic metastases. The ability to manipulate in vivo pharmacodynamics and tumor uptake of radiolabeled STh peptides through modification of linker moieties is under continuing investigation in order to produce optimal imaging and therapeutic radiopharmaceuticals.
 ...
PMID:In vitro and in vivo comparison of human Escherichia coli heat-stable peptide analogues incorporating the 111In-DOTA group and distinct linker moieties. 1526 76

An anthelminthic, pyrvinium pamoate (PP), 6-(dimethylamino)-2-[2-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)ethenyl]-1-methyl-quinolinium pamoate salt, has been found to be extremely toxic to PANC-1 cells in glucose-free medium, but not to be toxic to the same cells cultured in ordinary medium, Dulbecco's modified Eagle's medium (DMEM). It showed the same preferential toxicity for various cancer cell lines during glucose starvation. When 0.1 microg/ml PP was added to the medium, spheroid growth of human colon cancer cell line WiDr was strongly inhibited to a diameter of 750 microm, and this finding is consistent with the concept of anti-austerity. PP was also found to exert antitumor activity against human pancreatic cancer cell line PANC-1 in nude mice and SCID mice when it was administered subcutaneously or orally. Regarding the mechanism of PP action, inhibition of Akt phosphorylation, which has been found to be essential for the austerity mechanism, was observed in vitro and in vivo. These findings indicate that PP may be useful for anticancer therapy and that anti-austerity therapy could be a novel strategy for anticancer therapy.
 ...
PMID:Antitumor activity of pyrvinium pamoate, 6-(dimethylamino)-2-[2-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)ethenyl]-1-methyl-quinolinium pamoate salt, showing preferential cytotoxicity during glucose starvation. 1529 33

A number of receptor tyrosine kinases (RTKs) are involved in angiogenesis. TSU-68 (SU-6668) was developed as an inhibitor of RTKs involved in VEGF, bFGF and PDGF signaling, which then inhibits endothelial cell proliferation. We investigated the antitumor effects of TSU-68 against human colon cancer xenografts in male SCID mice and its anti-angiogenic activity using a dorsal air-sac (DAS) assay. TSU-68 was administered orally at a dose of 200 mg/kg twice daily. Mice bearing human colon carcinoma, HT-29, or WiDr xenografts were treated for 16 days. To determine the effect on hepatic metastasis, cell suspensions of HT-29 or WAV-I were injected into the spleen of mice on day 0, and mice treated for 28 days starting from day 1. For the DAS assay, HT-29, WiDr or WAV-I cells suspended in PBS at 2 x 10(7) cells/Millipore chamber were implanted subcutaneously into SCID mice, which were then treated from day 0 to 5, On day 6, the anti-angiogenic effects were assessed. Results indicated that TSU-68 significantly inhibited the growth of subcutaneous tumors. In the hepatic metastasis model, liver weights of the TSU-68-treated group were significantly reduced, compared to those of control mice. In the DAS assay, the angiogenic indices of the treated groups were significantly decreased for HT-29, WiDr and WAV-I tumors, with T/C ratios of 13.4, 50 and 35.3%, respectively. As TSU-68 significantly inhibited tumor growth and liver metastasis formation of human colon cancer xenografts, probably through anti-angiogenic activity, this agent may be useful for the treatment of colon cancer.
 ...
PMID:TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis. 1607 74

We have developed a novel single-chain Ep-CAM-/CD3-bispecific single-chain antibody construct designated MT110. MT110 redirected unstimulated human peripheral T cells to induce the specific lysis of every Ep-CAM-expressing tumor cell line tested. MT110 induced a costimulation independent polyclonal activation of CD4- and CD8-positive T cells as seen by de novo expression of CD69 and CD25, and secretion of interferon gamma, tumor necrosis factor alpha, and interleukins 2, 4 and 10. CD8-positive T cells made the major contribution to redirected tumor cell lysis by MT110. With a delay, CD4-positive cells could also contribute presumably as consequence of a dramatic upregulation of granzyme B expression. MT110 was highly efficacious in a NOD/SCID mouse model with subcutaneously growing SW480 human colon cancer cells. Five daily doses of 1 microg MT110 on days 0-4 completely prevented tumor outgrowth in all mice treated. The bispecific antibody construct also led to a durable eradication of established tumors in all mice treated with 1 microg doses of MT110 on days 8-12 after tumor inoculation. Finally, MT110 could eradicate patient-derived metastatic ovarian cancer tissue growing under the skin of NOD/SCID mice. MT110 appears as an attractive bispecific antibody candidate for treatment of human Ep-CAM-overexpressing carcinomas.
 ...
PMID:MT110: a novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors. 1613 92

The aim of this study was to design and prepare liposome-incorporated sclareol--a highly lipophilic natural product-to overcome its water insolubility and develop suitable formulations for in vivo administration. The bioactive labdane-type diterpene sclareol was incorporated into liposomes composed of egg phosphatidylcholine and dipalmitoylphosphatidylglycerol prepared by the thin-film hydration method followed by sonication. A formulation of egg phosphatidylcholine/dipalmitoylphosphatidylglycerol/sclareol (9:0.1:5 molar ratio) was developed and characterized. The lipid recovery and the sclareol to lipid molar ratio were measured using high-performance thin-layer chromatography/flame ionization detection. In vitro drug release was measured in supplemented RPMI-1640 at 37 degrees C. The liposomal and the free sclareol were initially tested in vitro for their activity against human cancer cell lines using the sulphorhodamine B assay. Liposomes incorporating sclareol at a drug to lipid molar ratio of 0:43, suggesting an incorporation efficiency of almost 80%, showed reduced growth rate of human colon cancer tumors (HCT116) developed in SCID mice, without any significant side effects.
 ...
PMID:Cytotoxic and antitumor activity of liposome-incorporated sclareol against cancer cell lines and human colon cancer xenografts. 1625 14

Research into the interaction between the E. coli heat-stable enterotoxin (STh) and the guanylin receptor guanylate cyclase C (GC-C) has generated >100 synthetic analogs of the peptide, several of which have been investigated as imaging or therapeutic agents for colorectal cancers. The evidence presented here suggests that in addition to STh binding to GC-C expressing cell lines derived from human colon, STh also specifically binds to an as yet unidentified receptor expressed in high densities on the surface of cell lines derived from human breast cancers. In vitro whole-cell crosslinking studies using 125I-labeled F19-STh(1-19) demonstrate that the putative STh binding protein migrates as an approximately 120-125 kDa species by SDS-PAGE, significantly smaller than the glycosylated GC-C molecule found in the T84 human colon cancer cell line. RT-PCR using total RNA isolated from breast and colon cancer cell lines indicates that GC-C transcripts are undetectable in human breast cancer cell lines and abundant in human colon cancer cell lines. In vitro competitive binding studies using STh analogs and the estrogen receptor positive (ER+) T-47D cell line demonstrated IC50 values between 2.6 and 8.5 nM. Similar studies on the estrogen receptor negative (ER-) cell line MDA-MB-231 showed IC50's between 5.6 and 9.9 nM. Saturation binding analysis revealed receptor expression to fall between 40,000 and 120,000 sites per cell in these cell lines, receptor abundances equal to or greater than the abundance of GC-C in colorectal cancer cell lines. STh binding to these cells, although of similar affinity to STh binding to GC-C, is distinguishable from it on the basis of its ligand specificity. The characteristics of STh analogs as radiopharmaceutical agents were tested in an in vivo model utilizing T-47D human breast cancer cell xenografts in SCID mice. Clearance of STh analogs was rapid, primarily via renal excretion into the urine, with >85% ID excreted into the urine at 1 h p.i. Tumor uptake at 1 h p.i. in T-47D tumor cell xenografts was 0.67+/-0.23% ID/g, and was significantly decreased (p<0.05) upon co-administration of 4 mg/kg unlabeled STh. These results suggest that STh may find application for the imaging and treatment of breast cancer.
 ...
PMID:In vitro and in vivo evaluation of 111In-labeled E. coli heat-stable enterotoxin analogs for specific targeting of human breast cancers. 1672 66

Recent advances in the design and preclinical evaluations of promising new generation taxane anticancer agents are reviewed in this article. Paclitaxel and docetaxel are two of the most important anticancer drugs today. However, recent reports have shown that treatment with these drugs often encounters undesirable side effects as well as drug resistance. Therefore, it is important to develop new taxane anticancer agents with fewer side effects, superior pharmacological properties, and improved activity against drug-resistant human cancers. Structure-activity relationship (SAR) studies led to the discovery of a series of highly active second-generation taxanes. One of them, "Ortataxel" (SB-T-101131, IDN5109, BAY59-8862), exhibits excellent activity against a variety of drug-sensitive and drug-resistant cancer cell lines, as well as human tumor xenografts in mice. It is orally active and is currently in phase II clinical trials. Photoaffinity labeling of microtubules and P-glycoprotein using photoreactive radiolabeled taxoids has disclosed the drug-binding domain of tubulin as well as Pgp. Together with information on microtubule-bound fluorine-labeled taxoids obtained by solid-state NMR studies, the bioactive conformation of paclitaxel and taxoids appears to emerge. Novel taxane-monoclonal antibody (mAb) immunoconjugates, have shown highly promising results for the tumor-specific delivery and release of an extremely cytotoxic, second-generation taxane. Also, another novel series of second generation taxanes conjugated with n-3 polyunsaturated fatty acids, e.g. decosahexaenoic acid (DHA), has exhibited impressive antitumor activity with minimum general toxicity against the highly drug-resistant DLD-1 human colon cancer xenografts in SCID mice.
 ...
PMID:Recent advances in the new generation taxane anticancer agents. 1678 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>