• Proceedings of the Materials Research Society of Korea Conference
• /
• 2011.05a
• /
• pp.52.2-52.2
• /
• 2011

Flat form technology for constructing anticancer loaded multi-walled carbon nanotubes (mwCNTs) was introduced in this study. Conventional anticancer drugs, such as MTX (Methotrexate), cisplatin, DOX (Doxorubicin hydrochloride), DAU (Daunorubicin) and EPI (epirubicin) were bio-conjugated with folic acid (FA) for selective targeting tumor cells. Loading efficiencies of the used anticancer drugs on mwCNTs have shown different order of bindings depending on the molecular bind affinity of NH (amine) formation on mwCNTs. MTT assays have shown increased selective target efficiency of FA conjugated mwCNTs on breast cancer cell growth inhibition. All results collectively indicated promising application of mwCNTs as a smart inorganic nanomaterial for selective targeting drug delivery vehicle at tumor tissues.

• Korean Journal of Clinical Pharmacy
• /
• v.5 no.2
• /
• pp.75-84
• /
• 1995

Drug delivery by red cells was established to maintain the release of drugs in the blood. The entrapment method by amphotericin B was re-examined and evaluated for obtaining the suitable entrapping conditions without hemolysis. The amphotericin B treatment below $10{\mu}g/ml$ induced the non-hemolysis to entrap daunorubicin into red cells within 10min. Under these conditions intracellular ATP level was decreased as $18\%$. Membrane fluidity and the shape factor of red cells were maintained. To maintain intracellular ATP, ATP and sodium pyruvate were added during the entrapment procedure because hemolysis during the release test would reflect the loss of intracellular ATP that would be postulate the decrease of the viability invivo. Consequently, the addition of ATP in the reaction solution can raise the intracellular level of ATP.

• Journal of the Korean Chemical Society
• /
• v.37 no.1
• /
• pp.141-147
• /
• 1993

A brief route for total synthesis of 6-deoxybisanhydrodaunomycinone(20) was described, namely the precursor of the daunomycinone, the aglycone of the anticancer antibiotic daunorubicin (1b). The prepared enone 4 was condensed with phthalide sulfone 7 to afford anthraquinone 10 after oxidation and methylation. The benzylic group of 10 was brominated, and subsequent oxidation with bis(tetrabutylammonium) dichromate followed by cyclization give hydroxyanthraquinone 16, which was displaced with thiophenol. Oxidation of 17 with m-CPBA in phosphate buffer solution afforded anthraquinonyl sulfone 18 which was condensed with methyl vinyl ketone (19) to furnish 20.

• YAKHAK HOEJI
• /
• v.41 no.6
• /
• pp.718-723
• /
• 1997

In the course of developing novel antitumor intercalating agents, we synthesized 3- carbamoyloxymethyl-azaanthraquinones 6-12, incorporating the latent alkylating functionality. These compounds were designed to explore the effect of heteroatom incorporation into anthraquinone chromophore and the effect of the incorporation of the latent alkylating functionality. The derivatives were prepared by hetero Diels-Alder reaction as a key step followed by functionality of allylic methyl to the desired substituents. Growth inhibitory studies of the azaanthraquinones were conducted in vitro against human cancer cell lines (SNU-354: liver and MCF7: breast) and human epidermoid carcinoma cells that are sensitive (KB-3-1) and multidrug-resistant (KB-V-1). The derivatives were 10 to 100-fold less potent than doxorubicin against sensitive cell lines. However, they were marginally cross-resistant with doxorubicin against KB-V-1.

• Journal of Microbiology and Biotechnology
• /
• v.2 no.3
• /
• pp.153-160
• /
• 1992

The doxorubicin resistance locus from Streptomyces peucetius subsp. caesius (the doxorubicin producer, ATCC 27952) has been cloned. The sequence data over 4.4 kb regions reveals the presence of four possible open reading frames (ORFs). ORF2 and ORF3 would encode proteins containing 329 and 283 amino acids, respectively. The protein encoded by ORF2 has two almost identical ATP binding domains with p-glycoprotein, the product of a multidrug resistance gene from tumor cells, and that encoded by ORF3 has several hydrophobic domains suggesting that it is located in the bacterial membrane. These two remarkable similarities of the gene product to p-glycoprotein of mammalian tumor cells suggest that the two proteins may enable bacteria to extrude a variety of toxic agents, including daunorubicin and doxorubicin, by an ATP dependent efflux mechanism analogous to the multidurg resistance protein of cancer cells.

• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.5
• /
• pp.513-523
• /
• 2018

The tumor microenvironment greatly influences cancer cell characteristics, and acidic extracellular pH has been implicated as an essential factor in tumor malignancy and the induction of drug resistance. Here, we examined the characteristics of gastric carcinoma (GC) cells under conditions of extracellular acidity and attempted to identify a means of enhancing treatment efficacy. Acidic conditions caused several changes in GC cells adversely affecting chemotherapeutic treatment. Extracellular acidity did inhibit GC cell growth by inducing cell cycle arrest, but did not induce cell death at pH values down to 6.2, which was consistent with down-regulated cyclin D1 and up-regulated p21 mRNA expression. Additionally, an acidic environment altered the expression of atg5, HSPA1B, collagen XIII, collagen XXAI, slug, snail, and zeb1 genes which are related to regulation of cell resistance to cytotoxicity and malignancy, and as expected, resulted in increased resistance of cells to multiple chemotherapeutic drugs including etoposide, doxorubicin, daunorubicin, cisplatin, oxaliplatin and 5-FU. Interestingly, however, acidic environment dramatically sensitized GC cells to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Consistently, the acidity at pH 6.5 increased mRNA levels of DR4 and DR5 genes, and also elevated protein expression of both death receptors as detected by immunoblotting. Gene silencing analysis showed that of these two receptors, the major role in this effect was played by DR5. Therefore, these results suggest that extracellular acidity can sensitize TRAIL-mediated apoptosis at least partially via DR5 in GCs while it confers resistance to various type of chemotherapeutic drugs.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.12
• /
• pp.5251-5256
• /
• 2016

Background: Diagnostic karyotyping analysis is routinely used in acute myeloid leukemia (AML) clinics. Categorization of patients into risk stratified groups (favorable, intermediate and adverse) according to cytogenetic findings can serve as a valuable independent prognostic factor. Method and Material: A retrospective descriptive study was conducted based on the patient records of newly diagnosed non-M3 AML young adult cases undergoing standard 3+7 i.e, Daunorubicin and Ara-C (DA) as remission induction chemotherapy. Diagnostic cytogenetic analysis reports were analyzed to classify the patients into risk stratified groups according to South West Oncology Group criteria and prognostic significance was measured with reference to achievement of haematological remission after 1st induction chemotherapy. Results:A normal karyotype was commonly expressed, found in 47.2% of patients, while 65% (n=39) appeared to have intermediate risk cytogenetics, and 13.3% (n=8) adverse or unclassified findings. Favourable cytogenetics was least frequent in the patient cohort, accounting for only 8.3 % (n=5).The impact of cytogenetic risk groups on achievement of haematological remission was evaluated by applying Pearson Chi-square, and was found to be non-significant (df=12, p=0.256) but when the outcomes of favourable risk groups with intermediate, adverse and unclassified findings compared, results were highly significant (df=6, p=0.000) for each comparison. In patients of the favourable cytogenetic risk group, HR?? was reported in 40% (n=2/5), as compared to 62.2% (n=23/37) in the intermediate cytogenetic risk group, 57.1% (n=4/7) in the adverse cytogenetic risk group and 28.6% (n=2/7) in hte unclassified cytogenetic risk group. Conclusion: Cytogenetic risk stratification for AML cases following criteria provided by international guidelines did not produce conclusive results in our Pakistani patients. However, we cannot preclude an importance as the literature clearly supports the use of pretreatment karyotyping analysis as a significant predictive marker for clinical outcomes. The apparent differences between Pakistani and Western studies indicate an urgent need to develop risk stratification guidelines according to the specific cytogenetic makeup of South Asian populations.

• Radiation Oncology Journal
• /
• v.12 no.2
• /
• pp.209-217
• /
• 1994

Between July 1987 and December 1992, we treated 22 patients with chronic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation(TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6fractions/3days (6 patients) or 1320 cGy/8 fractions/4days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were $58.5\%$ and $41.2\%$, respectively, and the relapse rate was $36\%$ among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase ($76\%\;vs\;33\%$, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation ($50\%\;vs\;0\%$, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patients remains in the chronic phase.

• Microbiology and Biotechnology Letters
• /
• v.26 no.1
• /
• pp.15-22
• /
• 1998

The dnrF gene, responsible for conversion of aklavinone to $\varepsilon$-rhodomycinone via C-11 hydroxylation, was mapped in the daunorubicin gene cluster of Streptomyces peucetius subsp. caesius ATCC 27952, close to drrAB, one of the anthracycline resistance genes. To characterize the enzymatic properties of the aklavinone 11-hydroxylase, the dnrF gene was overexpressed in Escherchia coli. The pET-22(+) plasmid which has the T7 promoter under the control of lacUV5 gene was used for the overexpression of the dnrF gene, and the recombinant plasmid pET213 that contains the dnrF gene linked to the T7 promoter of pET-22b(+) was introduced into the E. coli BL2l. When the expression of the dnrF gene was induced by IPTG at the final concentration of 1 mM, the induced protein could be detected in SDS-PAGE only in insoluble precipitate. The insoluble protein was electroeluted from the gel and used for the preparation of antiserum in mice. Various culture conditions were tested to maximize the expression of the aklavinone 11-hydroxylase in soluble form. The enzymatic activity was checked by the bioconversion experiment, and the protein was confirmed by the SDS-PAGE and the Western blot analysis. From the analysis of the data, it was concluded that the culture induced with IPTG at the final concentration of 0.02 mM at 37$^{\circ}C$ yielded the best productivity of active form of enzyme.

• KSBB Journal
• /
• v.20 no.3
• /
• pp.220-227
• /
• 2005

Doxorubicin is an anthracycline-family polyketide compound with a very potent anti-cancer activity, typically produced by Streptomyces peucetius. To understand the potential target biosynthetic genes critical for the doxorubicin everproduction, a doxorubicin-specific DNA microarray chip was fabricated and applied to reveal the growth-phase-dependent expression profiles of biosynthetic genes from two doxorubicin-overproducing strains along with the wild-type strain. Two doxorubicin-overproducing 5. peucetius strains were generated via over-expression of a dnrl (a doxorubicin-specific positive regulatory gene) and a doxA (a gene involved in the conversion from daunorubicin to doxorubicin) using a streptomycetes high expression vector containing a strong ermE promoter. Each doxorubicin-overproducing strain was quantitatively compared with the wild-type doxorubicin producer based on the growth-phase-dependent doxorubicin productivity as well as doxorubicin biosynthetic gene expression profiles. The doxorubicin-specific DNA microarray chip data revealed the early-and-steady expressions of the doxorubicin-specific regulatory gene (dnrl), the doxorubicin resistance genes (drrA, drrB, drrC), and the doxorubicin deoxysugar biosynthetic gene (dnmL) are critical for the doxorubicin overproduction in S. peucetius. These results provide that the relationship between the growth-phase-dependent doxorubicin productivity and the doxorubicin biosynthetic gene expression profiles should lead us a rational design of molecular genetic strain improvement strategy.