Biomedical subjects

S E Kim

Publications and source records attributed to S E Kim.

At least 37 records · Page 2Linked to original sources

PubMed2000

Modulatory effect of ginseng total saponin on dopamine release and tyrosine hydroxylase gene expression induced by nicotine in the rat.

Several studies have demonstrated that behavioral activation induced by psychostimulants is prevented by ginseng total saponin (GTS), which has been known to act on the central dopaminergic system. In an attempt to investigate whether the effect of GTS is through its inhibitory action on the elevated dopaminergic transmission, we examined the effect of GTS on nicotine-induced dopamine (DA) release in the nucleus accumbens (NA) of freely moving rats using in vivo microdialysis. Systemic injection of nicotine (3 mg/kg; i.p.) produced a mild increase in extracellular DA of dialysates samples in the NA (132+/-13% over basal levels at the peak). GTS (100 mg/kg; i.p.) had no effect on resting levels of extracelluar DA. However, an increase in accumbens DA release produced by systemic nicotine was completely blocked by systemic pre-treatment with GTS (100 mg/kg; i.p.). In addition, the effect of GTS on nicotine-induced tyrosine hydroxylase (TH) and immediate early gene expression in ventral tegmental area (VTA) or NA regions was examined. A single injection of nicotine increased TH mRNA level at VTA region. GTS, which did not affect the basal TH mRNA expression, attenuated nicotine-induced TH mRNA expression. Nicotine slightly increased both c-fos and c-jun mRNA level and GTS, which did not affect the basal c-fos and c-jun mRNA expression, further enhanced nicotine-induced c-fos and c-jun mRNA level at both VTA and NA regions. Our results suggest that GTS may have an inhibitory action against nicotine-induced DA release in NA region and TH mRNA expression in VTA region. GTS may exert an potentiative effect on both c-fos and c-jun mRNA expression at NA region through inhibiting the release of DA in NA.

Animals↗

PubMed2000

Syntheses and biological evaluation of (18)F-labeled 3-(1-benzyl-piperidin-4-yl)-1-(1-methyl-1H-indol-3-yl)propan-1-ones for in vivo mapping of acetylcholinesterase.

We synthesized novel (18)F-labeled acetylcholinesterase (AChE) inhibitors, 3-[1-(3- and 4-[(18)F]fluoromethylbenzyl)piperidin-4-yl]-1-(1-methyl-1H-i ndol-3-yl )propan-1-ones ([(18)F]1 and [(18)F]2) and 3-[1-(4-[(18)F]fluorobenzyl)piperidin-4-yl]-1-(1-methyl-1H-i ndol-3-yl )propan-1-one ([(18)F]3) in high yields (decay-corrected, 25%-40%) and with high effective specific activities (>37 GBq/micromol). Tissue distribution studies of the [(18)F]1 and the [(18)F]3 in mice showed the nonspecific bindings in brain regions, with metabolic defluorination of the [(18)F]1. The result suggests that these radioligands may not be suitable agents for in vivo mapping of AChE, despite their potent in vitro anti-AChE activities.

Acetylcholinesterase↗

PubMed2000

Synthesis and biological evaluation of 1-(4-[18F]fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine for in vivo studies of acetylcholinesterase.

We synthesized and evaluated 1-(4-fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine (4-FDP), which is an analog of donepezil. The 4-[(18)F]FDP was prepared by reductive alkylation of debenzylated donepezil with 4-[(18)F]fluorobenzaldehyde in high radiochemical yield (decay-corrected, 40-52%) and with high effective specific activity (30-38 GBq/micromol). Tissue distribution studies in mice demonstrated nonspecific distribution of the 4-[(18)F]FDP in brain regions, suggesting that this radioligand may not be a suitable agent for in vivo studies of acetylcholinesterase (AChE), despite its potent in vitro biological activity.

Acetylcholinesterase↗

PubMed2000

Brain tumor imaging with 99mTc-tetrofosmin: comparison with 201Tl, 99mTc-MIBI, and 18F-fluorodeoxyglucose.

The purpose of the present study was to assess the ability of technetium-99m-tetrofosmin (99mTc-TF) to predict tumor malignancy and to compare its uptake with that of thallium-201 (201Tl), technetium-99m-hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) and fluorine-18-fluorodeoxyglucose (18F-FDG) in brain tumors. 99mTc-TF single-photon emission computed tomography (SPECT) imaging was performed in 22 patients with brain tumors and 3 healthy controls. Some of the patients underwent 201Tl (n = 12) and 99mTc-MIBI SPECT (n = 14) and 18F-FDG positron emission tomography (PET) (n = 12). The radioactivity ratio of tumor to contralateral normal tissue (T/N) and the ratio of tumor to contralateral white matter (T/WM) were calculated in SPECT and PET images, respectively. In healthy controls, 99mTc-TF uptake was seen only in scalp, in the choroid plexus and pituitary gland, but not in normal cerebral parenchyma. TF T/N in low grade gliomas (2.8+/-0.4) was significantly lower than that in high grade gliomas (22.5+/-29.8) and malignant non-gliomas (8.3+/-2.8) without overlap of values (p = 0.003 and p = 0.014, respectively). TF T/N was significantly correlated with MIBI T/N (p = 0.92, p = 0.001), Tl T/N (p = 0.72, p = 0.017), and FDG T/WM (p = 0.65. p = 0.031). There was an excellent agreement between TF T/N and MIBI T/N values on linear regression analysis (MIBI T/N = -0.63+/-0.97 x TF T/N). These preliminary results indicate that SPECT imaging with 99mTc-TF may be useful for the non-invasive grading of brain tumors. They also suggest that 99mTc-TF and 99mTc-MIBI may accumulate in brain tumors by a similar mechanism or in relation to a similar process of tumor cell proliferation.

Adolescent↗

PubMed2000

Effect of ginseng total saponin on extracellular dopamine release elicited by local infusion of nicotine into the striatum of freely moving rats.

We investigated the effect of ginseng total saponin (GTS) on nicotine-induced dopamine (DA) release in the striatum of freely moving rats using an in vivo microdialysis technique. In order to further characterize the mechanism by which GTS affects DA release, the effect of GTS on K(+)-induced DA release was also examined. Local infusion of nicotine (1, 5, and 10 mM) into the striatum produced a dose-dependent increase in extracellular DA in dialysate samples (maximal response = 154.0 +/- 10.8%, 308.1 +/- 55.7%, and 499.9 +/- 77.9% over basal levels, respectively). GTS (100 mg/kg i.p.) had no effect on basal levels of extracellular DA. However, GTS inhibited maximal DA release induced by intrastriatal infusion of nicotine (1, 5, and 10 mM) by 35.3%, 36.6%, and 58.5%, respectively. Intra-striatal infusion of high K+ solution (100 mM) produced an increase in extracellular DA in the striatum (maximal response = 796.6 +/- 98.8% over basal levels). However, GTS had no effect on the K(+)-induced increase in extracellular DA. The present study demonstrated that GTS inhibited striatal DA release stimulated by local infusion of nicotine. This may reflect the blocking effect of GTS on the striatum-related behavior induced by nicotine as well as other psychostimulants. The results also suggest that GTS may act on presynaptic nicotinic acetylcholine receptors or receptor-operated Na+ channels in dopaminergic nerve terminals, but not on voltage-sensitive ion channels.

Animals↗

PubMed2000

Development of a miniature scintillation camera using an NaI(Tl) scintillator and PSPMT for scintimammography.

We have developed a small scintillation camera dedicated to breast imaging and have evaluated the performance of the system. In order to increase the limited field of view (FOV) determined by the size of a position-sensitive photomultiplier tube (PSPMT), the imaging characteristics of a diverging hole collimator (DHC) were also investigated. The small scintillation camera system consists of an NaI(Tl) crystal (60 mm x 60 mm x 6 mm) coupled to a Hamamatsu R3941 PSPMT, a resistor chain circuit, preamplifiers, nuclear instrument modules, an analogue to digital converter and a PC for control and display. The intrinsic energy resolution of the system was 12.9% FWHM at 140 keV. The spatial resolution was measured using a line-slit mask and 99mTc point sources and was 3.1 mm FWHM. The intrinsic sensitivity of the system was approximately 162 counts/s kBq(-1). The DHC made it possible to image a larger FOV (75 x 75 mm2 at the surface of collimator) than a parallel-hole collimator (60 x 60 mm2). The system sensitivity obtained using the DHC gradually decreased with distance (3% at 1 cm, 6% at 2 cm and 9% at 3 cm). The results demonstrate that the system developed in this study could be utilized clinically to image malignant breast tumours. A DHC can be employed to expand the FOV of the system confined by the size of PSPMT with a modest compromise in the performance of the system.

Breast Neoplasms↗

PubMed2000

Correlation of temporal lobe glucose metabolism with the Wada memory test.

PURPOSE: The goal of the present study was to examine the relationship of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and the Wada memory test in lateralizing memory dominance and epileptic focus. METHODS: FDG-PET and the Wada test were performed in 18 patients with temporal lobe epilepsy (TLE). The asymmetry indices of FDG-PET (PET-AI) were calculated in mesial, polar, anterolateral, midlateral, and posterolateral regions of the temporal lobe, and those of Wada memory test (Wada-AI) were obtained as well. RESULTS: The Wada-AI was significantly correlated with PET-AI in mesial (r = 0.67, p = 0.003), polar (r = 0.55, p = 0.019), anterolateral (r = 0.55, p = 0.019), and midlateral (r = 0.51, p = 0.031) regions of the temporal lobe. However, after a linear regression analysis, PET-AI of only the mesial temporal region was significantly correlated with Wada-AI (p = 0.008). Wada-AI could correctly lateralize the seizure focus in 90% of the left TLE and 75% of the right TLE patients. The PET-AI of the mesial temporal region showed the highest sensitivity of seizure lateralization (80% of left TLE and 87.5% of right TLE). PET-AI of other temporal regions had lower sensitivities (50-80% of left TLE, 20-75% of right TLE). One or two patients showed false seizure lateralization by PET-AI on each temporal region. CONCLUSIONS: Although FDG-PET hypometabolism is observed at both mesial and lateral regions of the temporal lobe in mesial TLE, mesial temporal region appeared to be a dominant and leading area for lateralizing Wada memory dominance and epileptic focus.

Adolescent↗

PubMed2000

Contralateral EEG slowing and amobarbital distribution in Wada test: an intracarotid SPECT study.

PURPOSE: To relate the occurrence of contralateral electroencephalogram slowing (CES) to amobarbital distribution, we performed electroencephalogram (EEG) monitoring and intracarotid single photon emission computed tomography (SPECT) during an intracarotid amobarbital procedure (IAP). METHODS: IAP was performed on 22 patients with temporal lobe epilepsy. CES was defined as the occurrence of significant EEG slowing on the contralateral hemisphere (>50% of the ipsilateral hemisphere slowing) after amobarbital injection. To map the distribution of the amobarbital, we injected a mixture of amobarbital and (99m)technetium-ethylcysteinate dimer (99mTc-ECD) into the internal carotid artery and performed a brain SPECT 2 h later. In the SPECT images, regions of interest were determined by ipsilateral and contralateral anterior cerebral artery territories (iACA, cACA), ipsilateral and contralateral middle cerebral artery territories (iMCA, cMCA), and ipsilateral and contralateral posterior cerebral artery territories (iPCA, cPCA), as well as ipsilateral and contralateral anterior and posterior mesial temporal regions (iAMT, cAMT, iPMT, cPMT). The perfusion of amobarbital was interpreted visually in each region. RESULTS: Amobarbital was distributed in the iMCA in all the patients; in the iACA in 20 (90.9%) patients; in the iAMT in 14 (63.5%); and in the iPCA and iPMT in only two (9.1%). CES was observed in 13 (59.1%) patients. Cross-perfusion of amobarbital in limited areas of the cACA were observed in only four of 13 patients. Wada retention memory scores (WRMS) showed no significant difference between the CES- (n = 9) and CES+ (n = 13) groups. CONCLUSIONS: Amobarbital rarely perfused the iPCA territory and the iPMT region and was rarely delivered to the contralateral hemisphere. The occurrence of CES was not related to the cross-perfusion of amobarbital. CES appears to be produced by a transient functional disconnection from the ipsilateral hemisphere.

Adolescent↗

PubMed2000

Preclinical impairment of the striatal dopamine transporter system in sporadic olivopontocerebellar atrophy: studied with [(123)I]beta-CIT and SPECT.

We investigated whether the dopamine (DA) transporter system is impaired in sporadic olivopontocerebellar atrophy (sOPCA) patients without clinical parkinsonism using the DA transporter radiotracer [(123)I]beta-CIT [2beta-carboxymethoxy-3beta-(4-iodophenyl)tropane] and single-photon emission computed tomography (SPECT). SPECT scans were acquired in 9 patients with sOPCA, 7 multiple system atrophy (MSA) patients with parkinsonism (MSA-P), and 7 age-matched healthy controls 20-24 h after the intravenous injection of [(123)I]beta-CIT. [(123)I]beta-CIT-specific binding in the striatum was determined as the radioactivity ratio of the striatum to the occipital cortex (specific binding ratio, SBR). In patients with sOPCA and MSA-P, SBRs in the right and left striatum and the mean SBR were significantly lower than those in controls (p < 0.05). The mean SBRs in patients with sOPCA and MSA-P were reduced to 69.0 and 60.7% of the control mean, respectively. However, there was no significant difference in SBRs between sOPCA and MSA-P patients. In sOPCA patients, the mean SBR was significantly correlated with the score of the clinical cerebellar function scale (r = -0.670, p = 0.024). These results indicate that even in the absence of clinical parkinsonism, the striatal dopaminergic system may be impaired in sOPCA. The DA transporter loss in sOPCA serves as another clue for sOPCA being a part of the spectrum of MSA.

Adult↗

PubMed2000

Broad specificity in binding of NIPP-1, nuclear inhibitor of protein phosphatase-1, to PP1 isoforms in vivo.

Protein phosphatase type-1 (PP1), one of the most abundant Ser/Thr protein phosphatases, plays a central role in the regulation of various cell functions. Almost all the PP1 molecules exist as holoenzymes in vivo consisting of a catalytic subunit (PP1C) and a variable regulatory subunit that regulates substrate specificity and/or subcellular localization. In order to clarify fine regulation of PP1, we overexpressed a nuclear inhibitor of PP1 (NIPP-1) in a Flag-tagged form in mammalian cells. The Flag-tagged NIPP-1 was found to be immunoprecipitated with three isoforms of PP1C, namely, PP1alpha, PP1gamma1, and PP1delta with a similar efficiency, suggesting that NIPP-1 makes a complex with the PP1C through the region conserved among the three isoforms. These results suggested that NIPP-1 can be involved in the regulation of various PP1 holoenzymes in vivo.

Animals↗

PubMed2000

Increased expression of NIPP-1 mRNA correlates positively with malignant phenotype in rat hepatomas.

In order to elucidate an involvement of protein phosphatase type 1 (PP1) in the malignant transformation, we have isolated rat cDNA for NIPP-1, a nuclear inhibitor for PP1. Rat NIPP-1 protein conserved the PP1 binding domain and the nuclear targeting sequence. The mRNA was ubiquitously expressed with the highest expression in bone marrow and thymus. The rat NIPP1 mRNA levels were slightly, if at all, increased in some primary hepatomas, and significantly increased in rat ascites hepatomas. The levels of NIPP-1 mRNA were closely correlated with malignant phenotype of rat ascites hepatomas, suggesting that NIPP-1 is tightly linked to malignant phenotype in hepatomas.

Amino Acid Sequence↗

PubMed2000

Cerebellar vasoreactivity in stroke patients with crossed cerebellar diaschisis assessed by acetazolamide and 99mTc-HMPAO SPECT.

UNLABELLED: Crossed cerebellar diaschisis (CCD) tends to persist or even worsen after supratentorial infarction. Several studies have shown impairment of cerebral vasomotor responsiveness in the hemispheric area of diaschisis in patients with hemispheric infarction. This finding has led to the concern that the lack of CCD reversibility might be associated with chronic circulatory abnormalities. We therefore assessed the vasoreactivity in the cerebellar hemisphere in which diaschisis is manifested using acetazolamide (ACZ) and SPECT. METHODS: Eight stroke patients with CCD (5 with unilateral hemispheric infarcts and 3 with unilateral intracerebral hemorrhage) had 99mTc-HMPAO SPECT scanning at rest and 20 min after intravenous injection of 1.0 g ACZ. The time interval after stroke ranged from 25 to 904 d. From the total counts obtained from each cerebellar hemisphere, the asymmetry index (AI) was calculated as (unaffected - affected cerebellar hemisphere)/unaffected cerebellar hemisphere x100. RESULTS: After ACZ, the mean AI (8.7+/-6.6) was significantly decreased (P<0.05) compared with that at rest (17.7+/-5.8). Seven of the 8 patients showed decrease in the AI after ACZ. In 1 patient, the direction of the asymmetry was reversed after ACZ so that the AI was negative. The ACZ-induced change in the AI did not show a significant correlation with the time interval after stroke, whether calculated in absolute terms or as a percentage change. CONCLUSION: This study shows that normal vascular supply is maintained in the CCD-affected cerebellar hemisphere over long periods of time after a stroke. Thus, the lack of CCD reversibility may not be attributed to a chronic circulatory insufficiency. The results lend support to the concept of functional deactivation and subsequent transneuronal degeneration as a likely explanation for CCD. It is unclear whether decreased AI after ACZ indicates a higher vascular response of the affected cerebellar hemisphere than that of the normal side.

Acetazolamide↗

PubMed2000

Improved detection of individual nodal involvement in squamous cell carcinoma of the esophagus by FDG PET.

UNLABELLED: Because both the number and location of metastatic lymph nodes and the N stage influence survival in esophageal cancer, accurate noninvasive evaluation of individual lymph node groups for the presence of metastasis is essential for therapeutic planning. Therefore, we investigated the accuracy of FDG PET for evaluating individual lymph groups in esophageal cancer patients and compared the results with those of CT and endoscopic sonography (ES). METHODS: Sixty-one consecutive patients with histologically proven primary esophageal carcinoma were studied prospectively with FDG PET. Thirteen patients who were treated nonsurgically were excluded from data analysis. The remaining 48 patients underwent esophagectomy and lymph node dissection. All 48 patients underwent CT scanning, including the lower neck, thorax, and upper abdomen, with intravenous administration of contrast medium. ES was performed in 45 of the patients but was incomplete in 12 patients because of esophageal stenosis. The accuracies of FDG PET, CT, and ES were compared with histologic findings. RESULTS: During surgery, a total of 382 lymph node groups were dissected in 48 patients, of which 100 node groups in 32 patients were malignant on histologic examination. For assessing metastasis to individual groups, FDG PET showed 57% sensitivity, 97% specificity, and 86% accuracy, whereas CT showed 18% sensitivity (P < 0.0001), 99% specificity (P = 0.033), and 78% accuracy (P = 0.003). For N staging, FDG PET was correct in 83% (40/48) of the patients, whereas CT and ES were correct in 60% (29/48; P = 0.006) and 58% (26/45; P = 0.003), respectively. CONCLUSION: FDG PET is more accurate than is CT or ES for evaluating metastasis to individual lymph node groups and for N staging in esophageal cancer and thus may be helpful in determining the therapeutic plan.

Aged↗

PubMed1999

Diffusion-weighted magnetic resonance imaging in probable Creutzfeldt-Jakob disease: a clinical-anatomic correlation.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rare transmissible disease that typically causes a rapidly progressive dementia and leads to death in less than 1 year. Although a few anecdotal reports suggest that diffusion-weighted magnetic resonance imaging may help substantiate premortem diagnosis of CJD, detailed correlation between radiographic data and clinical, electrophysiologic, and metabolic parameters is not available. METHODS: Signal abnormalities on diffusion-weighted images in 3 consecutive patients with probable CJD were correlated with psychometric features, electroencephalographic findings, and functional images with either positron emission tomography or single photon emission computed tomography. RESULTS: Focality of abnormalities on diffusion-weighted image, not apparent on routine magnetic resonance images, correlated closely with clinical manifestations of CJD. The topographic distribution of signal abnormality on diffusion-weighted image corresponded with abnormal metabolism or perfusion on positron emission and single photon emission computed tomographic scans. In 2 cases, the laterality of diffusion abnormalities correlated with periodic sharp wave activity on electroencephalograms. CONCLUSION: These findings extend previous observations that suggested a diagnostic and localizing utility of diffusion-weighted imaging in CJD.

Aged↗

PubMed1999

Effect of tracer metabolism on PET measurement of [11C]pyrilamine binding to histamine H1 receptors.

The present study was carried out to investigate the time course of [11C]pyrilamine metabolism and the degree of entry of metabolites into the brain. PET studies were performed in seven healthy volunteers and arterial plasma concentrations of [11C]pyrilamine and its labeled metabolites were determined. After intravenous injection, [11C]pyrilamine metabolized gradually in the human body, with less than 10% of plasma activity being original radioligand at 60 min. Tracer metabolism markedly affected the input function and the calculated impulse response function of the brain. Rat experiments demonstrated that although metabolites of [11C]pyrilamine might enter the brain, they were not retained for prolonged periods of time. At 30-90 min after injection of [11C]pyrilamine, less than 1% of the radioactivity in the brain was originating from metabolites of [11C]pyrilamine. Based on the rat data, the contribution of 11C-labeled metabolites to total [11C]pyrilamine radioactivity in the human brain was estimated and found to be negligible. These results suggest that the metabolites of [11C]pyrilamine do not accumulate within the cerebral extravascular space and that there is minimal metabolism of [11C]pyrilamine by brain tissue itself. Therefore, [11C]pyrilamine metabolites can be neglected in kinetic analysis, using either a compartmental or a noncompartmental model, of the [11C]pyrilamine binding to histamine H1 receptors.

Adult↗

PubMed1999

Ginsenoside-Rs4, a new type of ginseng saponin concurrently induces apoptosis and selectively elevates protein levels of p53 and p21WAF1 in human hepatoma SK-HEP-1 cells.

In this paper, we present evidence that ginsenoside-Rs4 (G-Rs4; an acetylated analogue of ginsenoside-Rg5), a new ginseng saponin isolated from Panax ginseng C. A. Meyer, elevates protein levels of p53 and p21WAF1, which are associated with the induction of apoptosis in SK-HEP-1 cells. Flow cytometric analyses showed that G-Rs4 initially arrested the cell cycle at the G1/S boundary, but consequently induced apoptosis as evidenced by generating an apoptotic peak. The induction of apoptosis was confirmed by the results of DNA fragmentation assays and alterations in cell morphology after treatment of the cells with G-Rs4. Immunoblot assays showed that G-Rs4 significantly elevated protein levels of p53 and p21WAF1, concurrently with the downregulation of both cyclins E- and A-dependent kinase activities and induction of apoptosis. We suggest that G-Rs4 induces apoptosis, the effect of which is closely related to the downregulation of both cyclins E- and A-dependent kinase activity as a consequence of selectively elevating protein levels of p53 and p21WAF1 in SK-HEP-1 cells.

Apoptosis↗

PubMed1999

Sesquiterpene esters from Celastrus orbiculatus and their structure-activity relationship on the modulation of multidrug resistance.

Six new (1-6) and three known (7-9) sesquiterpene esters were isolated from the roots of Celastrus orbiculatus. The structures of the new compounds were elucidated as 1beta-acetoxy-6alpha-furoyloxy-9alpha-benzoyl oxydihydro-beta-agarofur an (1), 1beta-acetoxy-6alpha-benzoyloxy-9alpha-furoyloxydih ydro-beta-agarofur an (2), 1beta-acetoxy-6alpha, 9alpha-difuroyloxydihydro-beta-agarofuran (3), 1beta, 2beta-diacetoxy-6alpha-furoyloxy-9alpha-benzo yloxydihydro-beta-agarof uran (4), 1beta-acetoxy-2beta, 6alpha-difuroyloxy-9alpha-benzoyloxydihydro-beta -agarofuran (5), and 1beta-acetoxy-2beta,6alpha, 9alpha-tribenzoyloxydihydro-beta-agarofuran (6). Compounds 4, 5, and 7-9 were shown to be more active than verapamil in reversing vinblastine resistance in multidrug-resistant KB-V1 cells.

Cell Survival↗

PubMed1999

Pregnane glycoside multidrug-resistance modulators from Cynanchum wilfordii.

The methanol-soluble extracts of the roots of Cynanchum wilfordii showed a significant multidrug-resistance-reversing activity, and four known pregnane glycosides were isolated by bioassay-directed fractionation and separation. Their structures were identified as gagaminin 3-O-beta-D-cymaropyranosyl-(1-->4)-beta-D-oleandropyranosyl- (1-->4)-b eta-D-cymaropyranosyl-(1-->4)-beta-D-cymaropyranoside (1), wilfoside K1N (2), wilfoside C1N (3), and cynauricuoside A (4). In particular, compound 1, at a concentration level of 1 microM, was found to completely reverse the multidrug-resistance of KB-V1 and MCF7/ADR cells to adriamycin, vinblastine, and colchicine.

Antineoplastic Agents↗