PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 2092934

Fuzzy adaptive least squares and its use in quantitative structure-activity relationships.

I Moriguchi·S Hirono·Q A Liu·Y Matsushita·T Nakagawa
View original source ↗Export metadata ↓

Abstract

Fuzzy adaptive least squares (FALS), a pattern recognition method designed to correlate molecular structure with activity rating, has been developed. A novel feature of FALS is that the degree to which each sample belongs to an activity class is given using a membership function. The algorithm involves an iterative modification of forcing factors to maximize the sum of the membership function values over all samples. This paper first describes the method and calculation procedure of FALS89 (1989 version of FALS), and then shows its application to the correlation of structure with a potency rating of anticarcinogenic mitomycin derivatives and arginine-vasopressin antagonists. FALS89 applied to these samples showed considerably high reliability in both recognition and leave-one-out prediction.

Explore related subjects

Antibiotics, AntineoplasticArginine VasopressinMitomycinsStatistics as TopicStructure-Activity RelationshipJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

I Moriguchi, S Hirono, Q A Liu, Y Matsushita, T Nakagawa. 1990. Fuzzy adaptive least squares and its use in quantitative structure-activity relationships.. https://doi.org/10.1248/cpb.38.3373

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

The application of Fe3O4 nanoparticles in cancer research: a new strategy to inhibit drug resistance.

Although much effort has been extended to the efficient cancer therapies, the drug resistance is still a major obstacle in cancer chemotherapeutic treatments. Almost 90% of the cancer therapy failure is caused by the relative problems. Recently, the application of drug coated polymer nanospheres and nanoparticles to inhibit the related drug resistance has attracted much attention. In this report, we have explored a novel strategy to inhibit the multidrug resistance of the targeted tumor cells by combining the unique properties of tetraheptylammonium capped Fe(3)O(4) magnetic nanoparticles with the drug accumulation of anticancer drug daunorubicin. Our results of confocal fluorescence and atomic force microscopy (AFM) as well as electrochemical studies demonstrate the remarkable synergistic effect of Fe(3)O(4) nanoparticles on drug uptake of daunorubicin in leukemia K562 cells. These observations indicate that the interaction between the magnetic nanoparticles Fe(3)O(4) and biologically active molecules on the membrane of leukemia cell lines may contribute to their beneficial effect on cellular uptake so that the synergistic enhanced effect of magnetic nanoparticles Fe(3)O(4) on drug uptake of drug resistance leukemia K562 cells could be observed upon application of the Fe(3)O(4) nanoparticles.

Antibiotics, Antineoplastic↗
PubMed2007

Balance of NF-kappaB and p38 MAPK is a determinant of radiosensitivity of the AML-2 and its doxorubicin-resistant cell lines.

This study investigated radioresistance mechanisms in the doxorubicin-resistant acute myelogenous leukemia (AML)-2/DX100. AML-2/DX100 also showed resistance to radiation. AML-2/DX100 characterized by down-regulated catalase expression was supersensitive to exogenous hydrogen peroxide whereas they increased defense mechanisms against endogenous reactive oxygen species (ROS) as compared with AML-2/WT. In AML-2/WT, radiation increased Bax expression and its translocation to mitochondria but had little effect on translocation of Bcl-2 and consequently induced the release of cytochrome c from the mitochondria with the subsequent caspase-3 activation. On the contrary, in AML-2/DX100, radiation neither increased Bax expression nor its translocation to mitochondria while it increased Bcl-2 translocation to mitochondria. A specific p38 MAPK inhibitor SB203580 increased radioresistance in AML-2/WT but little in AML-2/DX100. It inhibited radiation-induced Bax translocation in AML-2/WT but not in AML-2/DX100, indicating that p38 MAPK is working after irradiation in AML-2/WT but not in AML-2/DX100. Electrophoretic mobility shift assay and Western blot analysis revealed that NF-kappaB in AML-2/DX100 was more activated with degradation of cytosolic IkappaBalpha than was that of AML-2/WT. cDNA microarray showed that Bfl-1/A1 and granzyme H in AML-2/DX100 were highly up-regulated (6.21-fold) and down-regulated (6.49-fold), respectively, as compared with each of AML-2/WT, which were confirmed by RT-PCR assay. Taken together, these results indicate that radioresistance mechanisms of AML-2/DX100 could be related to alterations in ROS-scavenging activity, in mitochondrial translocation of Bax and Bcl-2, and in expression of pro-apoptotic (granzyme H) and anti-apoptotic (Bfl-1/A1) genes. It has been shown that balance of p38 MAPK and NF-kappaB signals is a determinant in radiosensitivity of AML-2/WT and AML-2/DX100.

Antibiotics, Antineoplastic↗
PubMed2007

pPSX: a novel vector for the cloning and heterologous expression of antitumor antibiotic gene clusters.

A cosmid cloning vector has been constructed that demonstrates high levels of segregational stability in Escherichia coli K12. pPSX is a 14-kilobase vector derived from the IncW plasmid pR388. pPSX is highly stable in E. coli in the absence of antibiotic selection, even while expressing the toxic indolocarbazole antitumor antibiotic violacein. The incorporation of the lambdacos sequence enables construction of cosmid libraries with inserts ranging from 24 to 36kb. The inclusion of a lacZalpha multiple cloning site (MCS) allows blue/white screening. pPSX cosmids can be extracted from the host cell with commercial plasmid extraction kits facilitating downstream analysis, sequencing and sub-cloning. pPSX can be transferred to a variety of heterologous hosts by either electroporation or mobilization from E. coli S17-1. While it is unstable in non-E. coli hosts without antibiotic selection, heterologous host strains such as Rhodobacter sphaeroides and Pseudomonas stutzeri will maintain the plasmid under antibiotic selection to allow screening of expressed inserts. pPSX provides the benefits of large insert sizes with high stability to allow cloning of chemotherapeutic gene clusters in E. coli and a range of other heterologous hosts.

Antibiotics, Antineoplastic↗