A Novel Water-Soluble Heptaplatin Analogue with Improved Antitumor Activity and Reduced Toxicity

2011 ◽  
Vol 50 (12) ◽  
pp. 5324-5326 ◽  
Author(s):  
Weiping Liu ◽  
Xizhu Chen ◽  
Qingsong Ye ◽  
Yongping Xu ◽  
Chengying Xie ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Water Soluble ◽  
Reduced Toxicity

Novel water soluble phosphate prodrugs of taxol® possessing in vivo antitumor activity

1993 ◽  
Vol 3 (8) ◽  
pp. 1761-1766 ◽  
Author(s):  
Yasutsugu Ueda ◽  
Amarendra B. Mikkilineni ◽  
Jay O. Knipe ◽  
William C. Rose ◽  
Anna Maria Casazza ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Water Soluble ◽  
Soluble Phosphate ◽  
In Vivo Antitumor Activity

scholarly journals Epigallocatechin Gallate-Gold Nanoparticles Exhibit Superior Antitumor Activity Compared to Conventional Gold Nanoparticles: Potential Synergistic Interactions

Nanomaterials ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 396 ◽  
Author(s):  
Suhash Chavva ◽  
Sachin Deshmukh ◽  
Rajashekhar Kanchanapally ◽  
Nikhil Tyagi ◽  
Jason Coym ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Nuclear Translocation ◽  
Epigallocatechin Gallate ◽  
Drug Carriers ◽  
Water Soluble ◽  
Tetrazolium Salt ◽  
Uptake Studies

Epigallocatechin gallate (EGCG) possesses significant antitumor activity and binds to laminin receptors, overexpressed on cancer cells, with high affinity. Gold nanoparticles (GNPs) serve as excellent drug carriers and protect the conjugated drug from enzymatic metabolization. Citrate-gold nanoparticles (C-GNPs) and EGCG-gold nanoparticles (E-GNPs) were synthesized by reduction methods and characterized with UV-visible spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Cytotoxicity of citrate, EGCG, C-GNPs, and E-GNPs was evaluated by the water-soluble tetrazolium salt (WST-1) assay. Nanoparticle cellular uptake studies were performed by TEM and atomic absorption spectroscopy (AAS). Dialysis method was employed to assess drug release. Cell viability studies showed greater growth inhibition by E-GNPs compared to EGCG or C-GNPs. Cellular uptake studies revealed that, unlike C-GNPs, E-GNPs were taken up more efficiently by cancerous cells than noncancerous cells. We found that E-GNP nanoformulation releases EGCG in a sustained fashion. Furthermore, data showed that E-GNPs induced more apoptosis in cancer cells compared to EGCG and C-GNPs. From the mechanistic standpoint, we observed that E-GNPs inhibited the nuclear translocation and transcriptional activity of nuclear factor-kappaB (NF-κB) with greater potency than EGCG, whereas C-GNPs were only minimally effective. Altogether, our data suggest that E-GNPs can serve as potent tumor-selective chemotoxic agents.

DX-8951f, a Hexacyclic Camptothecin Analog, on a Daily-Times-Five Schedule: A Phase I and Pharmacokinetic Study in Patients With Advanced Solid Malignancies

2000 ◽  
Vol 18 (17) ◽  
pp. 3151-3163 ◽  
Author(s):  
Eric K. Rowinsky ◽  
Thomas R. Johnson ◽  
Charles E. Geyer ◽  
Lisa A. Hammond ◽  
S. Gail Eckhardt ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Dose Level ◽  
Compartment Model ◽  
Maximum Tolerated Dose ◽  
Preliminary Evidence ◽  
Water Soluble ◽  
Severe Thrombocytopenia ◽  
Phase Ii Studies ◽  
Solid Malignancies ◽  
Wide Range

PURPOSE: To assess the feasibility of administering DX-8951f (exatecan mesylate), a water-soluble, camptothecin analog, as a 30-minute intravenous infusion daily for 5 days every 3 weeks, determine the maximum-tolerated dose (MTD) and pharmacokinetic (PK) behavior of DX-8951f, and seek preliminary evidence of anticancer activity. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of DX-8951f. After three patients were treated at the first dose level, doses were to be escalated in increments of 100%, using a single patient at each dose level unless moderate toxicity was observed. The MTD, defined as the highest dose level at which the incidence of dose-limiting toxicity did not exceed 20%, was calculated separately for minimally pretreated (MP) and heavily pretreated (HP) patients. The PK and excretory profiles of DX-8951, the anhydrous form of DX-8951f, were also characterized. RESULTS: Thirty-six patients were treated with 130 courses of DX-8951f at six dose levels ranging from 0.1 to 0.6 mg/m2/d. Brief, noncumulative neutropenia was the most common toxicity observed. Severe myelosuppression (neutropenia that was protracted and/or associated with fever and/or severe thrombocytopenia) was consistently experienced by HP and MP patients at doses exceeding 0.3 and 0.5 mg/m2/d, respectively. Nonhematologic toxicities (nausea, vomiting, and diarrhea) were also observed, but these effects were rarely severe. Objective antitumor activity included partial responses in one patient each with platinum-resistant extrapulmonary small-cell and fluoropyrimidine- and irinotecan-resistant colorectal carcinoma, and minor responses in patients with prostate, hepatocellular, thymic, primary peritoneal, and irinotecan-resistant colorectal carcinomas. The PKs of total DX-8951 were linear and well fit by a three-compartment model. CONCLUSION: The recommended doses for phase II studies of DX-8951f as a 30-minute infusion daily for 5 days every 3 weeks are 0.5 and 0.3 mg/m2/d for MP and HP patients, respectively. The characteristics of the myelosuppressive effects of DX-8951f, paucity of severe nonhematologic toxicities, and antitumor activity against a wide range of malignancies warrant broad disease-directed evaluations of DX-8951f on this schedule.

Physicochemical Characterization and Antitumor Activity of Water-Soluble Polysaccharides from Bupleurum chinense

2015 ◽  
Vol 51 (5) ◽  
pp. 939-940
Author(s):  
Haibin Tong ◽  
Feng-e Li ◽  
Zhongmei He ◽  
Xiangfu Song ◽  
Shuwen Guan ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Physicochemical Characterization ◽  
Water Soluble

A preclinical survey on the efficacy of NSC-290205 in combination with doxorubicin (ADR) in Lewis lung carcinoma (LLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17131-17131
Author(s):  
A. Papageorgiou ◽  
E. Stergiou ◽  
I. Boukovinas ◽  
G. Geromichalos ◽  
I. Stergiou
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Maximum Effect ◽  
Base Pairs ◽  
Chop Regimen ◽  
C57bl Mice ◽  
Inhibition Of Tumor Growth ◽  
Reduced Toxicity ◽  
The Right ◽  
Derivatives Of

17131 Background: NSC-290205 (A) is a hybrid synthetic antitumor ester, which combines a D-lactam derivative of androsterone and nitrogen mustard. Studies on modified steroidal esters of carboxylic derivatives of N,N-bis(2-chloroethyl)aniline, have shown that they exhibit reduced toxicity and increased antitumor activity and specificity. In this study we investigated the antitumor activity of compound A in combination with ADR (AHOP) in comparison with standard CHOP regimen. Methods: C57Bl mice were used for the antitumor evaluation of AHOP/CHOP. Experiments were initiated by implanting the tumor. LLC cells (purchased by NCI, Bethesda, USA) were implanted intramuscularly into the right hind leg as a suspension of 7 × 106 cells in 0.1 ml. The antitumor activity was assessed from the inhibition of tumor growth by volume in cm3 and the oncostatic parameter T/C % according to the protocol of experimental evaluation of antitumor drugs of the NCI, USA. Treatments were given as a single dose (D) on day 1, intermitted dose (D/2 × 3) on days 1, 5, 9 or consecutive dose (D/4 × 9) on days 1 through 9. Results: Treatment with A or cyclophosphamide produced almost equal borderline activity. Moreover, both CHOP and AHOP regimens showed significant and comparable antitumor effect (p < 0.05 by the Wilkoxon test). AHOP caused the maximum effect inhibiting the tumor growth by 67.7% and T/C values of 270%. CHOP was less effective producing 54.8% tumor inhibition and T/C values of 238%. Conclusions: It is very likely that the D-lactamic steroid (androstan) alkylator for A, containing the -NHCO group, combined with ADR, which intercalates between base-pairs, is the explanation for higher activity of AHOP vs. CHOP. This significant effect of NSC-290205 with the anthracycline adriamycin on LLC adds to NSC-290205 advantage for further clinical development. No significant financial relationships to disclose.

Antitumor Activities of Extracts and Compounds from Water Decoctions of Taxus cuspidata

2010 ◽  
Vol 38 (06) ◽  
pp. 1107-1114 ◽  
Author(s):  
Shougang Jiang ◽  
Yu Zhang ◽  
Yuangang Zu ◽  
Zhuo Wang ◽  
Yujie Fu
Keyword(s):  
Antitumor Activity ◽  
Water Soluble ◽  
Taxus Cuspidata ◽  
Antitumor Activities ◽  
Antitumor Effects ◽  
Anticancer Properties ◽  
Specific Host ◽  
First Time

Water decoctions from the leaves of Taxus cuspidata are used in traditional Chinese medicine to treat cancer, suggesting that water soluble constituents from these leaves may possess anticancer properties. Interestingly, hydrophilic paclitaxel derivatives, as opposed to paclitaxel itself, can be detected by high pressure liquid chromatography in water decoctions from these leaves. The remainder extracts, which are free of paclitaxel and hydrophilic paclitaxel derivatives, from the T. cuspidata leaves were investigated for antitumor activity in vivo and in vitro for the first time in this study. EE80B, 7-xylosyl-10-deacetylpaclitaxel and 7-xylosyl-10-deacetylpaclitaxel C displayed the most antitumor activity in vivo. However, in vitro studies with tumor cell lines showed that EE80B had a significantly smaller antitumor effect than paclitaxel. We hypothesize that water decoctions from T. cuspidata leaves exhibit antitumor effects in vivo, which may be aided by the activation of specific host mechanisms (e.g. stimulation of antitumor immunity) which are not present in vitro.

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