Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of aprotinin, EACA and heparin on the growth of the transplanted rodent Murphy-Sturm lymphosarcoma and on several components of the tumor kinin-forming enzyme system was studied. Therapy was administered for 15 days, 3 times daily, one day after tumor transplant. Tumor weights and biochemical parameters (prekallikrein, kininogen and kininase) were measured on the 8th, 10th, 12th and 15th day of therapy. Both aprotinin and heparin significantly inhibited (p less than 0.01) tumor growth by the 15th day, compared to control, saline-administered animals. EACA did not affect the tumor growth rate at any time period. Tumor prekallikrein and kininogen levels were significantly higher (p less than 0.01) in the aprotinin-treated animals. Kininogen levels were higher in the EACA-treated tumors during the latter phase of growth. None of the agents affected the increase in tumor kininase activity that occured during the growth of the tumors. The tumor inhibition and biochemical data suggest the involvement of proteases in the neoplastic process.
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PMID:Effect of aprotinin, EACA and heparin on growth and vasopeptide system of Murphy-Sturm lymphosarcoma. 108 54

Experimental and clinical data suggest that tissue factor (TF), the major initiator of blood coagulation cascade, as well as proteases and components of the fibrinolytic system are involved in tumor growth at least in some solid tumors via effects on angiogenesis. Whereas the pro- and anti-angiogenic effects of the plasminogen/plasmin system and plasminogen kringle domains, respectively, are well characterized, the pathways responsible for the pro-angiogenic properties of TF remain poorly understood. To learn more about the biological significance of the recently described binding of plasminogen to the extracellular domain of TF, we examined the effects of soluble TF (sTF) on angiostatin-inhibited proliferation of endothelial cells. In solid phase binding assays, we found that sTF binds specifically to plasminogen, to the plasminogen kringle domains K1-3, K1-5, K4, as well as to mini-plasminogen. Inhibition of binding of plasminogen and its kringle domains to sTF by the lysine analog 6-aminohexanoic acid (AHA) suggests that lysine-binding sites are involved in plasminogen interaction with TF. Moreover, in the presence of sTF, the inhibitory effect of K1-5 on bFGF-mediated HUVEC proliferation was dose-dependently and saturably abolished. This suggests that TF can interfere with the antagonistic effect of K1-5 on endothelial cell proliferation. In contrast, sTF by itself had no effect on the endothelial cell proliferation. Whereas the interference of TF with K1-5-mediated effect was prevented by AHA, this lysine analog did not abolish the proliferation inhibition of K1-5. In conclusion, the binding of sTF to the plasminogen fragment K1-5 seems to antagonize the anti-angiogenic effects of this plasminogen fragment.
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PMID:Soluble tissue actor interferes with angiostatin-mediated inhibition of endothelial cell proliferation by lysine-specific interaction with plasminogen kringle domains. 1252 59

Angiostatin, the N-terminal four kringles (K1-4) of parent molecule plasminogen, is reported to block Lewis Lung Carcinoma (LLC) tumor growth and metastasis. However, angiostatin's mechanism of action is unclear. We earlier reported that angiostatin binds to cell surface annexin II through the lysine-binding domain (kringles 1-4) [Tuszynski, G.P., Sharma, M., Rothman, V.L., Sharma, M.C., 2002. Angiostatin binds to tyrosine kinase substrate annexin II through the lysine-binding domain in endothelial cells. Microvasc. Res. 64:448-462.]). We now show that annexin II on the cell surface of LLC cells regulates conversion of plasminogen to plasmin. Activation of plasminogen to plasmin is time-dependent, with the linear activation lasting up to 120 min. Monoclonal antibodies to annexin II reduced plasminogen activation by 92.6%, suggesting a specific role of annexin II in plasmin generation. Angiostatin also reduced plasmin generation by 81.6%, suggesting that angiostatin may be competing with plasminogen through lysine-binding domain. epsilon-Aminocaproic acid, a lysine analogue, effectively blocked plasminogen activation indicating that, indeed, the lysine-binding site of the kringles domain is required for activation. These data suggest that annexin II may be a receptor target for angiostatin's action. Therefore, we tested the effect of high affinity monoclonal antibody to annexin II in mouse model of LLC. A single dose of antibody treatment inhibited LLC tumor growth almost 70% with concomitant inhibition of circulating plasmin generation and its proteolytic activity. Taken together, it is possible that inhibition of LLC tumor growth and metastasis reported by angiostatin therapy may be due to blocking of annexin-II-dependent plasmin generation. Plasmin is known to influence angiogenic, invasive and metastatic capability of tumors.
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PMID:Antibody-directed targeting of angiostatin's receptor annexin II inhibits Lewis Lung Carcinoma tumor growth via blocking of plasminogen activation: possible biochemical mechanism of angiostatin's action. 1664 91

Cisplatin (CDDP) was incorporated inside single-wall carbon nanohorns with holes opened (SWNHox) by a nanoprecipitation method that involved dispersion of CDDP and SWNHox in a solvent followed by the solvent evaporation. The incorporated CDDP quantity increased from the previously reported value of 15 to 46%, and the total released quantity of CDDP also increased from 60 to 100% by changing the solvent from dimethylformamide to water. Concurrently, in vitro anticancer efficiency of CDDP@SWNHox increased to 4-6 times greater than that of the intact CDDP. In vivo, CDDP@SWNHox intratumorally injected to transplanted tumors of mice suppressed the tumor growth more than the intact CDDP. We observed that CDDP@SWNHox adhered to the cell surfaces in vitro and stayed within the tumor tissues in vivo. Therefore, we think that the CDDP released from SWNHox realized high concentrations locally at the cells in vitro and in the tissues in vivo and could efficiently attack the tumor cells. We also found that SWNHox itself had an in vivo anticancer effect, which might increase the anticancer activities of CDDP@SWNHox.
ACS Nano 2008 Oct 28
PMID:Enhancement of in vivo anticancer effects of cisplatin by incorporation inside single-wall carbon nanohorns. 1920 52

Carbon nanotube-based drug delivery holds great promise for cancer therapy. Herein we report the first targeted, in vivo killing of cancer cells using a drug-single wall carbon nanotube (SWNT) bioconjugate, and demonstrate efficacy superior to nontargeted bioconjugates. First line anticancer agent cisplatin and epidermal growth factor (EGF) were attached to SWNTs to specifically target squamous cancer, and the nontargeted control was SWNT-cisplatin without EGF. Initial in vitro imaging studies with head and neck squamous carcinoma cells (HNSCC) overexpressing EGF receptors (EGFR) using Qdot luminescence and confocal microscopy showed that SWNT-Qdot-EGF bioconjugates internalized rapidly into the cancer cells. Limited uptake occurred for control cells without EGF, and uptake was blocked by siRNA knockdown of EGFR in cancer cells, revealing the importance of EGF-EGFR binding. Three color, two-photon intravital video imaging in vivo showed that SWNT-Qdot-EGF injected into live mice was selectively taken up by HNSCC tumors, but SWNT-Qdot controls with no EGF were cleared from the tumor region in <20 min. HNSCC cells treated with SWNT-cisplatin-EGF were also killed selectively, while control systems that did not feature EGF-EGFR binding did not influence cell proliferation. Most significantly, regression of tumor growth was rapid in mice treated with targeted SWNT-cisplatin-EGF relative to nontargeted SWNT-cisplatin.
ACS Nano 2009 Feb 24
PMID:Targeted killing of cancer cells in vivo and in vitro with EGF-directed carbon nanotube-based drug delivery. 1923 65

Antiangiogenesis is an effective strategy for cancer treatment because uncontrolled tumor growth depends on tumor angiogenesis and sufficient blood supply. Great progress has been made in developing a "molecular" form of angiogenesis inhibitors; however, the narrow inhibition spectrum limits anticancer efficacy as those inhibitors that usually target a few or even a single angiogenic factor among many angiogenic factors might initially be effective but ultimately lead to the failure of the treatment due to the induction of expression of other angiogenic factors. In this work, we report that with a multiple hydroxyl groups functionalized surface, the Gd@C(82)(OH)(22) fullerenic nanoparticles (f-NPs) are capable of simultaneously downregulating more than 10 angiogenic factors in the mRNA level that is further confirmed at the protein level. After studying this antiangiogenesis activity of the f-NPs by cellular experiment, we further investigated its anticancer efficacy in vivo. A two-week treatment with the f-NPs decreased >40% tumor microvessels density and efficiently lowered the speed of blood supply to tumor tissues by approximately 40%. Efficacy of the treatment using f-NPs in nude mice was comparable to the clinic anticancer drug paclitaxel, while no pronounced side effects were found. These findings indicate that the f-NPs with multiple hydroxyl groups serve as a potent antiangiogenesis inhibitor that can simultaneously target multiple angiogenic factors. We propose that using nanoscale "particulate" itself as a new form of medicine (particulate medicine) may be superior to the traditional "molecular" form of medicine (molecular medicine) in cancer treatment.
ACS Nano 2010 May 25
PMID:Potent angiogenesis inhibition by the particulate form of fullerene derivatives. 2042 77

A series of doxorubicin-loaded polymer-caged nanobins (PCN(DXR)) were evaluated in vivo in a murine MDA-MB-231 xenograft model of triple-negative breast cancer. The cross-linked polymer cage in PCN(DXR) offers protection for the drug payload while serving as a pH-responsive trigger that enhances drug release in the acidic environments commonly seen in solid tumors and endosomes. Varying the degree of cross-linking in the polymer cage allows the surface potential of PCN(DXR), and thus the in vivo circulation lifetime of the nanocarriers, to be tuned in a facile fashion. Given these design advantages, the present study provides the first in vivo evidence that PCN(DXR) can effectively inhibit tumor growth in a murine model of breast cancer. Importantly, PCN(DXR) was well-tolerated by mice, and drug encapsulation attenuated the toxicity of free doxorubicin. Taken together, this study demonstrates the potential utility of the PCN platform in cancer therapy.
ACS Nano 2010 Sep 28
PMID:Biological evaluation of pH-responsive polymer-caged nanobins for breast cancer therapy. 2087 86

Stearate-g-dextran (Dex-SA) was synthesized via an esterification reaction between the carboxyl group of stearic acid (SA) and hydroxyl group of dextran (Dex). Dex-SA could self-assemble to form nanoscaled micelles in aqueous medium. The critical micelle concentration (CMC) depended on the molecular weight of Dex and the graft ratio of SA, which ranged from 0.01 to 0.08 mg mL(-1). Using doxorubicin (DOX) as a model drug, the drug encapsulation efficiency (EE%) using Dex-SA with 10 kDa molecular weight of Dex and 6.33% graft ratio of SA could reach up to 84%. In vitro DOX release from DOX-loaded Dex-SA micelles (Dex-SA/DOX) could be prolonged to 48 h, and adjusted by a different molecular weight of Dex, the graft ratio of SA, or the drug-loading content. Tumor cellular uptake test indicated that Dex-SA micelles had excellent internalization ability, which could deliver DOX into tumor cells. In vitro cytotoxicity tests demonstrated the Dex-SA/DOX micelles could maintain the cytotoxicity of commercial doxorubicin injection against drug-sensitive tumor cells. Moreover, Dex-SA/DOX micelles presented reversal activity against DOX-resistant cells. In vivo antitumor activity results showed that Dex-SA/DOX micelles treatments effectively suppressed the tumor growth and reduced the toxicity against animal body compared with commercial doxorubicin injection.
ACS Nano 2010 Nov 23
PMID:Synthesis and antitumor activity of stearate-g-dextran micelles for intracellular doxorubicin delivery. 2093 8

Stat3 is a latent transcription factor that promotes cell survival and proliferation and is often constitutively active in multiple cancers. Inhibition of Stat3 signaling pathways suppresses cell survival signals and leads to apoptosis in cancer cells, suggesting direct inhibition of Stat3 function is a viable therapeutic approach. Herein, we identify a small molecule, C48, as a selective Stat3-family member inhibitor. To determine its mechanism of action, we used site-directed mutagenesis and multiple biochemical techniques to show that C48 alkylates Cys468 in Stat3, a residue at the DNA-binding interface. We further demonstrate that C48 blocks accumulation of activated Stat3 in the nucleus in tumor cell lines that overexpress active Stat3, leading to impressive inhibition of tumor growth in mouse models. Collectively, these findings suggest Cys468 in Stat3 represents a novel site for therapeutic intervention and demonstrates the promise of alkylation as a potentially effective chemical approach for Stat3-dependent cancers.
ACS Chem Biol 2011 May 20
PMID:Alkylation of cysteine 468 in Stat3 defines a novel site for therapeutic development. 2122 22

A gold nanorod (GNR)-photosensitizer complex was developed for noninvasive near-infrared fluorescence imaging and cancer therapy. We showed that (a) fluorescence emission and singlet oxygen generation by AlPcS(4) were quenched after complex formation with GNRs; (b) 4-fold greater intracellular uptake and better in vitro phototoxicity were observed in GNR-AlPcS(4)-treated cells than in free AlPcS(4)-treated cells; and (c) after intravenous injection of the GNR-AlPcS(4) complex, tumor sites were clearly identified on near-infrared fluorescence images as early as 1 h after injection. The tumor-to-background ratio increased over time and was 3.7 at 24 h; tumor growth reduced by 79% with photodynamic therapy (PDT) alone and by 95% with dual photothermal therapy (PTT) and PDT. This novel multifunctional nanomedicine may be useful for near-infrared fluorescence imaging and PTT/PDT in various cancers.
ACS Nano 2011 Feb 22
PMID:Gold nanorod-photosensitizer complex for near-infrared fluorescence imaging and photodynamic/photothermal therapy in vivo. 2124 12


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