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Biomedical subjects

M Kawada

Publications and source records attributed to M Kawada.

At least 19 recordsLinked to original sources
PubMed1999

Cytostatin, an inhibitor of cell adhesion to extracellular matrix, selectively inhibits protein phosphatase 2A.

Cytostatin, which is isolated from a microbial cultured broth as a low molecular weight inhibitor of cell adhesion to extracellular matrix (ECM), has anti-metastatic activity against B16 melanoma cells in vivo. In this study, we examined a target of cytostatin inhibiting cell adhesion to ECM. Cytostatin inhibited tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin upon B16 cell adhesion to fibronectin. While the amount of FAK was not affected by cytostatin, electrophoretically slow-migrating paxillin appeared. Alkaline phosphatase treatment diminished cytostatin-induced slow-migrating paxillin. Furthermore, cytostatin increased intracellular serine/threonine-phosphorylated proteins and was found to be a selective inhibitor of protein phosphatase 2A (PP2A). Cytostatin inhibited PP2A with an IC(50) of 0.09 microgram/ml in a non-competitive manner against a substrate, p-nitrophenyl phosphate, but it had no apparent effect on other protein phosphatases including PP1, PP2B and alkaline phosphatase even at 100 microgram/ml. On the contrary, dephosphocytostatin, a cytostatin analogue, without inhibitory effect on PP2A did not affect B16 cell adhesion including FAK and paxillin. These results indicate that cytostatin inhibits cell adhesion through modification of focal contact proteins such as paxillin by inhibiting a PP2A type protein serine/threonine phosphatase. This is the first report that describes a drug with anti-metastatic ability that inhibits PP2A selectively.

Animals↗
PubMed1999

Axially chiral 1,7-naphthyridine-6-carboxamide derivatives as orally active tachykinin NK(1) receptor antagonists: synthesis, antagonistic activity, and effects on bladder functions.

Cyclic analogues of N-[3,5-bis(trifluoromethyl)benzyl]-7,8-dihydro-N, 7-dimethyl-5-(4-methylphenyl)-8-oxo-1,7-naphthyridine-6-carboxamide (1) having a 6-9-membered ring (6-9) were synthesized and evaluated for NK(1) antagonistic activities. The 8-membered ring compound with a beta-methyl group at the C((9))-position, (aR,9R)-7-[3, 5-bis(trifluoromethyl)benzyl]-8,9,10, 11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g] [1, 7]naphthyridine-6,13-dione [(aR,9R)-8b], was atropodiastereoselectively synthesized by cyclization of a chiral intermediate, 10g. On the other hand, the 7-membered ring compound with a beta-methyl group at the C((9))-position [(9S)-7b] was obtained as an equilibrium mixture of atropisomers with a ratio of ca. 3:2 in solution at room temperature (measured by NMR in CDCl(3)). Compounds (9S)-7b and (aR,9R)-8b exhibited excellent antagonistic activities both in vitro [IC(50) (inhibition of [(125)I]BH-SP binding in human IM-9 cells) = 0.28 and 0.45 nM, respectively] and in vivo (iv and po). Significantly, the in vitro activity of (aR, 9R)-8b was ca. 750-fold higher than that of its enantiomer (aS, 9S)-8b, ca. 40-fold higher than its atropisomer (aS,9R)-8b, and ca. 20-fold higher than its diastereomer (aR,9S)-8b. The structure-activity relationships in this series, along with the X-ray analysis of (aR,9R)-8b, indicated that the stereochemistry around the -C((6))(=O)-N((7))-CH(2)Ar moiety is important for NK(1) receptor recognition. The NK(1) antagonists showed effects on bladder functions in guinea pigs upon intravenous injection: i.e., the antagonists increased the shutdown time of distension-induced rhythmic bladder contractions and the bladder volume threshold, and the effects on the shutdown time were found to correlate well with the NK(1) antagonistic activities. Compound (aR,9R)-8b has been identified as a potential clinical candidate for the treatment of bladder function disorders.

Animals↗
PubMed1999

NA22598, a novel antitumor compound, reduces cyclin D1 levels, arrests cell cycle at G1 phase, and inhibits anchorage-independent growth of human tumor cells.

NA22598, a novel antitumor compound isolated from a microbial cultured broth, inhibited the growth of human colon cancer DLD-1 cells in suspension cultures (anchorage-independent growth) severalfold more strongly than in substratum-attached monolayer cultures. It arrested the cell cycle progression at early G1 phase under both these culture conditions. Rb phosphorylation, cyclin D1 expression, and cdk2 activation in G1 progression were all inhibited by NA22598, but the amounts of cdk2 and p27 were not affected. Among these effects the inhibition of cyclin D1 expression was most prominent, and NA22598 was found to inhibit the synthesis of cyclin D1 without affecting mRNA expression or protein degradation. p27 binding to cdk2 was more markedly increased in suspension cultures than in attached cultures by NA22598, but the compound had no effect on total p27. Apparently, the decrease of cyclin D1 induced redistribution of p27 from the cyclin D1/cdk4 to the cyclin E/cdk2 complexes during G1 phase in the suspension cultures. Because p27 is upregulated during suspension culture, a greater amount of it was associated with cyclin E/cdk2, thus producing greater growth inhibition. An agent, like NA22598, which induces the downregulation of cyclin D1 might offer a new anticancer strategy.

Antineoplastic Agents↗
PubMed1999

Differential induction of apoptosis in B16 melanoma and EL-4 lymphoma cells by cytostatin and bactobolin.

Most solid tumor cells are less sensitive to apoptosis induced by anticancer drugs than hematopoietic cancer cells. However, the mechanisms of the different responses to apoptosis in these cell types remain unknown. To explore this question, we used B16 melanoma and EL-4 lymphoma cells as solid tumor- and hematopoietic cancer-derived cell lines, and examined the effects of two apoptosis inducers, cytostatin and bactobolin, on both cell lines. Apoptosis in B16 cells was induced strongly by bactobolin, but weakly by cytostatin. In contrast, apoptosis in EL-4 cells was induced strongly by cytostatin, but weakly by bactobolin. While caspase-3 was activated upon induction of apoptosis in both cell lines, Ac-DEVD-CHO, a specific inhibitor of caspase-3, suppressed only the apoptosis in B16 cells. In B16 cells, cyclins E, A, and B1 were decreased by strongly apoptosis-inducing bactobolin prior to apoptosis commitment, but cyclin E was not decreased by weakly apoptosis-inducing cytostatin. On the other hand, in EL-4 cells cyclins D1, E, A, and B1 were decreased by strongly apoptosis-inducing cytostatin prior to apoptosis commitment, but neither cyclin A nor B1 was decreased by weakly apoptosis-inducing bactobolin. These results indicate that the dependency of apoptosis induction on caspase activity is different between the two cell lines. Furthermore, there may be an inverse correlation between specific cyclins and apoptosis induction in the two cell lines.

Animals↗
PubMed1999

Enhancement of antiproliferative effects of interleukin-1beta and tumor necrosis factor-alpha on human prostate cancer LNCaP cells by coculture with normal fibroblasts through secreted interleukin-6.

The cell-cell interactions between tumor cells and stromal cells are considered to be important in the regulation of tumor development at primary and metastatic secondary sites. We studied the effects of various cytokines on the cell-cell interactions between androgen-dependent LNCaP or androgen-independent PC-3 human prostate cancer cell lines and normal fibroblasts using a co-culture system. Among the tested combinations of cytokines and fibroblasts, strong modulations of cytokine actions were seen in coculture with human normal fibroblasts WI-38. While interleukin (IL)-1beta or tumor necrosis factor-alpha (TNF-alpha) partially suppressed LNCaP cell growth in monoculture, each cytokine completely inhibited it in the case of coculture with WI-38 cells. On the other hand, they did not inhibit PC-3 cell growth significantly, regardless of monoculture or coculture. Conditioned medium prepared from WI-38 cells pretreated with IL-1beta or TNF-alpha also strongly inhibited LNCaP cell growth. In the conditioned medium, marked IL-6 secretion was induced from WI-38 cells by IL-1beta or TNF-alpha. Furthermore, neutralizing antibodies to IL-6 or IL-6 receptor abrogated the antiproliferative effects of IL-1beta- and TNF-alpha-pretreated WI-38 conditioned medium. These results demonstrate that the antiproliferative effects of IL-1beta and TNF-alpha on prostate cancer cells are enhanced by coculture with normal fibroblasts through some diffusible factor(s), such as IL-6, from the stimulated fibroblasts.

Androgens↗
PubMed1999

[Intratumoral ethanol injection therapy using endoscopic video information system].

Bronchoscopic ethanol injection (BEI) therapy for endobronchial malignant tumor is thought to be an effective modality for airway dilatation and hemostasis without expensive special equipment. But if ethanol leaks into the airway, it causes severe coughing and erosion of bronchial wall. Using endoscopic video information system (EVIS), an assistant operator can observe an ethanol leak and inject an adequate volume. To evaluate the efficacy and adverse effect of BEI therapy, we treated 8 patients with endobronchial malignant tumor using EVIS. Under local anesthesia, a video-bronchoscope (Olympus BF200 or BF 1T200) was inserted orally, a transbronchial aspiration cytology (TBAC) needle was inserted via the biopsy channel, and injections of 0.2 ml of 99% ethanol into the tumor were repeated. After the tumor degenerated to necrotic tissue, it was removed with a biopsy forceps, and this maneuver was repeated for the existing fresh lesion. The total volume of injected ethanol was 4.5 + 1.6 ml (mean + SD). Airway obstruction and atelectasis were relieved in 4 cases, and hemostasis was obtained in 2 cases. In 2 cases, airway dilatation and hemostasis were not obtained. BEI was more effective in the patients with polypoid or nodular tumor protruding into the airway lumen. As for adverse effects, ethanol leaks caused a severe cough in 2 cases, although they were tolerable and treatment could be continued. BEI therapy using EVIS was thought to be useful to control airway obstruction by endobronchial polypoid tumor with good cost-effectiveness and fewer adverse effects.

Bronchial Neoplasms↗
PubMed1998

Axially chiral N-benzyl-N,7-dimethyl-5-phenyl-1, 7-naphthyridine-6-carboxamide derivatives as tachykinin NK1 receptor antagonists: determination of the absolute stereochemical requirements.

A potent and orally active NK1 antagonist, trans-N-[3, 5-bis(trifluoromethyl)benzyl]-7,8-dihydro-N, 7-dimethyl-5-(4-methylphenyl)-8-oxo-1,7-naphthyridine-6-carboxamide (1t), was shown to exist as a mixture of separable and stable (R)- and (S)-atropisomers (1t-A and 1t-B) originating from the restricted rotation around the -C(6)-C(=O)- bond; the antagonistic activities of 1t-A were ca. 6-13-fold higher than those of 1t-B. Analogues of 1t (3), which have (S)- and (R)-methyl groups at the benzylic methylene portion of 1t, were prepared and separated into the diastereomeric atropisomers, 3a-A, 3a-B and 3b-A, 3b-B, in enantiomerically pure forms. Among the four isomers of 3, the (aR, S)-enantiomer (3a-A) exhibited the most potent antagonistic activities with an IC50 value of 0.80 nM (in vitro inhibition of [125I]BH-SP binding in human IM-9 cells) and ED50 values of 9.3 micrograms/kg (iv) and 67.7 micrograms/kg (po) (in vivo inhibition of capsaicin-induced plasma extravasation in guinea pig trachea), while the activity of the (aS,R)-enantiomer (3b-B) was the weakest with an IC50 value of 620 nM. The structure-activity relationships in this series of antagonists indicate that the (R)-configuration at the axial bond and the stacking (or stacking-like) conformation between the two phenyl rings as shown in 1t-A and 3a-A are essential for high-affinity binding and suggest that the amide moiety functions as a hydrogen bond acceptor in the interaction with the receptor.

Administration, Oral↗
PubMed1998

[Successful repair of critical aortic stenosis with coarctation on the first day of life].

Successful open aortic valvotomy and end-to-end anastomosis were performed to the patient with critical aortic stenosis and CoA on the first day of life. A fetus was diagnosed as aortic stenosis and coarctation by fetal echocardiography at 29 weeks of gestation. The mother was transferred to our hospital at the onset of labor and delivered vaginally at 40 weeks of gestation. Soon after the birth, the newborn, birth weight 2630 gram, female, underwent echocardiography by pediatric cardiologists which demonstrated the aortic orifice of 5.1 mm in diameter and thickened cusps with poor mobility. Transaortic pressure gradient measured by Doppler echocardiography was 111 mmHg and the left ventricular wall motion was hyperdynamic without any signs of endocardial fibroelastosis. Prostaglandin E1 administration was started to maintain systemic circulation and the hemodynamic status has been stable before surgery. On her first day of life, the operation was performed using cardiopulmonary bypass with moderate hypothermia. Isolated cerebral and myocardial perfusion technique was applied during the repair of coarctation of the aorta. The open aortic valvotomy with resection of myoxomatous nodules on leaflet edges effectively released pressure gradient across the aortic valve without regurgitation. Post-operative course was uneventful and she discharged at 28th day after surgery. We conclude early diagnosis including fetal echocardiography and early repair would lead the better surgical outcome to the neonates with critical aortic stenosis.

Alprostadil↗
PubMed1998

[Norwood procedure to hypoplastic left heart syndrome].

Since March 1992, 25 neonates and small infants with HLHS have undergone a modified Norwood procedure. The mean age and weight at operation were 17 days (2 days-2 months) and 2.7 kg (1.6-3.3 kg). Isolated cerebral and/or myocardial perfusion (ICMP) with direct anastomosis of aorta and pulmonary artery was utilized since January 1995 to 16 patients. Under median sternotomy, PTFE graft (usually 3.0-3.5 mm) was anastomosed to the brachiocephalic artery and the arterial cannula was inserted to this PTFE graft. The left carotid and the left subclavian arteries were snared and a clamp was placed on the aortic arch just distal to the brachiocephalic artery. This allowed blood to enter the brain and the coronary arteries, keeping the brain perfused and the heart-beating. After reconstruction of distal aortic arch, a single dose of crystalloid cardioplesia was infused and the rest of the arch was reconstructed. There were 14 early deaths (56%) and 4 late deaths (16%). Bidirectional Glenn procedure was performed to 5 patients with 1 death. Three patients underwent modified Fontan procedure without mortality. Mean aortic cross clamp time was 24 min. and mean ICMP time was 32 min. There was no neurologic complications. In conclusion, isolated cerebral and/or myocardial perfusion may offer an advantage of protecting the brain and myocardium during arch in Norwood procedure.

Aorta↗
PubMed1998

Massive culture of human liver cancer cells in a newly developed radial flow bioreactor system: ultrafine structure of functionally enhanced hepatocarcinoma cell lines.

With a view to initiating clinical trials, cell morphology and function for a newly developed artificial liver support system employing highly functional human liver cell line, FLC-7, cultured in a radial flow bioreactor were compared to cells grown in a conventional monolayer culture. The radial flow bioreactor consists of a vertically extended cylindrical matrix comprised of porous glass bead microcarriers through which liquid medium flows from the periphery in toward the central axis generating a beneficial concentration gradient of oxygen and nutrients, while preventing excessive shear stresses or buildup of waste products. The three-dimensional culture system supports high-density (1.1 x 10(8) cells/ml-matrix), large scale cultures (4.4 x 10(10) cells/400 ml-bioreactor) with long-term viability. Scanning and transmission electron microscopy (SEM and TEM) revealed that cells cultured in a monolayer system were flattened and extended with numerous cytoplasmic projections. Cells in the three-dimensional culture were spherical and covered with microvillilike processes resembling liver cells in vivo. The cells were solidly attached on the surfaces and within the pores of the microcarriers in highly dense colonies. The spherical cells remained in close contact with adjacent cells, while circulation of liquid medium flowed freely through spaces between cells. FLC-7 cells produced albumin at a rate of 6.41 micrograms/24 h/10(6) cells. Alpha-fetoprotein (AFP) production dropped nearly threefold in comparison to monolayer cultures. Results demonstrated that the new artificial liver support systems (ALSS) provides a superior three-dimensional culture environment that allows cells to perform at naturally functioning levels.

Bioreactors↗
PubMed1998

Decay-accelerating factor (DAF) in stool specimens as a marker of disease activity in patients with ulcerative colitis (UC).

Colonic epithelial cells of patients with UC express DAF in relation to the severity of mucosal inflammation. The aim of this study was to determine whether this factor in stool could be used as a marker of disease activity in UC patients. Stool DAF was measured by use of an immunoassay in 181 stool specimens obtained from 55 patients with UC of various levels of disease activity. Stool DAF concentrations in patients whose UC was active (0.0-785.6 ng/g stool; median 47.1 ng/g; n = 115) were significantly higher than concentrations in patients whose disease was inactive (0.0-48.6 ng/g; median 0.0 ng/g; n = 66) (P < 0.0001). Values in active UC patients also were higher than those in control patients with diarrhoea (0.0-30.0 ng/g; median 0.0 ng/g; n = 26) (P < 0.0001) and in control subjects without apparent colorectal disease (0-20.4 ng/g; median 0.0 ng/g; n = 44) (P < 0.0001). The elevated levels of stool DAF obtained from UC patients in relapse declined markedly in specimens collected after the disease went into remission following medical therapy. Stool DAF levels correlated with the severity of endoscopic and histological findings and the degree of DAF expression on the colonic epithelia. Our results suggest that the measurement of stool DAF is useful as a non-invasive means of monitoring intestinal disease activity in patients with UC.

Adolescent↗
PubMed1998

Cytokine-stimulated release of decay-accelerating factor (DAF;CD55) from HT-29 human intestinal epithelial cells.

Expression of DAF (CD55) is enhanced on colonic epithelial cells of patients with ulcerative colitis (UC), and stool DAF concentrations are increased in patients with active disease. Cytokines are known to modulate DAF expression in various human cells, and lesions of UC reveal altered profiles of cytokine production. In this study, we evaluate the effects of various cytokines, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, and interferon-gamma (IFN-gamma), on the synthesis and kinetics of DAF protein in HT-29 human intestinal epithelial cells. Using flow cytometry and an ELISA, we found that HT-29 cells constitutively express DAF on the cell surface and spontaneously release DAF into the culture supernatant under standard culture conditions. When the culture supernatant was centrifuged at 100000g, nearly a half of DAF was precipitated, indicating that one half of the released DAF was present as a membrane-bound form and the other half as a soluble form. Analysis of the culture supernatant of biotin surface-labelled HT-29 cells suggested that the soluble form DAF was derived by secretion from within the cell or by cleavage from the cell surface. Among the cytokines, IL-4 markedly, and IL-1beta moderately, enhanced the expression and the release of DAF. Actinomycin D, cycloheximide, and brefeldin A inhibited the increase in DAF release induced by IL-4 and IL-1beta stimulation. These results suggest that DAF is released from intestinal epithelial cells in response to cytokine stimulation and that IL-4 and IL-1beta are possible cytokines involved in DAF release into the colonic lumen of patients with UC.

Anti-Bacterial Agents↗
PubMed1998

Up-regulation of p27Kip1 correlates inversely with anchorage-independent growth of human cancer cell lines.

We examined the correlation between anchorage-independent growth and cell cycle-related molecules using 39 human cancer cell lines. They consisted of lung-, colon-, stomach-, breast-, ovarian-, brain-, renal- and melanoma-derived cell lines. Their anchorage-independent growth ability varied, but was not clearly related to the tissue of origin. There was a tendency for the levels of cyclin D1, cyclin E, cyclin A, p27, and p21 to show a tissue-dependent expression pattern. Statistical analysis revealed an inverse correlation of the p27 level with anchorage-independent growth (r=-0.456, P<0.01). Thus, the regulation of p27 is suggested to be linked to the anchorage independence of human cancer cells.

Cell Adhesion↗
PubMed1998

Cardiovascular effects of (2RS,3SR)- 2-aminomethyl-2,3,7,8-tetrahydro-2,3,5,8,8-pentamethyl-6H-furo- [2,3-e]indol-7-one hydrochloride (UK-1745), a novel cardiotonic agent with vasodilatory and antiarrhythmic properties.

The cardiovascular effects of (2RS,3SR)-2-aminomethyl-2,3,7,8- tetrahydro-2,3,5,8,8-pentamethyl-6H-furo[2,3-e]indol-7-one hydrochloride (CAS 170684-14-7, UK-1745), a novel cardiotonic agent, were investigated using in vitro and in vivo preparations. In paced left atria isolated from guinea pigs, both UK-1745 and vesnarinone (CAS 81840-15-5) showed a concentration-dependent positive inotropic effect. In spontaneously beating guinea pig right atria, both agents caused only a minimal chronotropic effect. In isolated, blood-perfused canine papillary muscle preparations, UK-1745 and vesnarinone injected intra-arterially into the anterior septal artery (ASA) increased the developed tension in a dose-dependent manner. In isolated, blood-perfused canine sinoatrial node preparations, both agents injected into the right coronary artery (RCA) did not cause any appreciable changes in the sinus rate. UK-1745 increased the blood flow through the ASA and the RCA in a dose-dependent manner, whereas vesnarinone did not. In anesthetized open-chest dogs, UK-1745 injected intravenously increased cardiac contractility and cardiac output, and decreased left ventricular end-diastolic pressure, systemic vascular resistance and heart rate. In experimentally induced acute heart failure in anesthetized open-chest dogs, intravenously injected UK-1745 effectively improved hemodynamic functions. In conscious instrumented dogs, orally administered UK-1745 increased LV dP/dtmax with insignificant changes in systemic blood pressure and heart rate. In mice, orally administered UK-1745 protected the development of ventricular fibrillation induced by chloroform inhalation, whereas vesnarinone did not. Thus, in respect of inotropic and chronotropic effects, UK-1745 closely resembled vesnarinone, but differed from vesnarinone in respect of coronary vasodilating and antiarrhythmic effects. The results suggest that UK-1745 is a novel positive inotropic agent with vasodilatory and antiarrhythmic properties, without significant chronotropic action, and may be beneficial for the treatment of congestive heart failure.

Anesthesia↗
PubMed1998

High density culture of immortalized liver endothelial cells in the radial-flow bioreactor in the development of an artificial liver.

Liver endothelial cells are important components of the tissue along the hepatic sinusoid. They are responsible for microcirculation in the liver and scavenger functions. It would therefore be important to include these cells in any hybrid type of artificial liver in addition to hepatocytes. However, it is difficult to culture these cells in vitro. The development of a liver endothelial cell line, which maintains the characteristics of the primary culture, would thus be of great benefit in the development of an artificial liver. In the present study we established immortalized liver endothelial cells from the liver of an H-2Kb-tsA58 transgenic mouse, which harbors the SV40 TAg gene. Hepatic sinusoidal cells isolated from H-2Kb-tsA58 mouse proliferated in the presence of gamma-interferon at 33 degrees C. Four clones were established, out of which clone M1 had the highest amounts of PGI2 production, as well as plasminogen activator activity and internalized acetylated low density lipoprotein. On culture dishes the M1 cells grew individually and spread. Sieve plates on the cell surface were not readily visible, but small pores were detected under electron microscopic observation. These results suggest that M1 clone cells originated from liver endothelial cells. Moreover it was possible to culture the immortalized liver endothelial cells in a radial-flow bioreactor for 5 days, with a maximum 6-keto prostaglandin F1alpha production of 25 microg per day. This suggests that immortalized liver endothelial cells and a radial-flow bioreactor can prove useful tools in the development an artificial liver.

Animals↗
PubMed1997

Induction of p27Kip1 degradation and anchorage independence by Ras through the MAP kinase signaling pathway.

While most untransformed cells require substrate attachment for growth (anchorage dependence), the oncogenic transformed cells lack this requirement (anchorage independence) and are often tumorigenic. However, the mechanism of loss of anchorage dependence is not fully understood. When rat normal fibroblasts were cultured in suspension without substrate attachment, the cell cycle arrested in G1 phase and the cyclin-dependent kinase inhibitor p27Kip1 protein and its mRNA accumulated. Conditional expression of oncogenic Ras induced the G1-S transition of the cell cycle and significantly shortened the half-life of p27Kip1 protein without altering its mRNA level. Inhibition of the activation of mitogen-activated protein (MAP) kinase by cyclic AMP-elevating agents and a MEK inhibitor prevented the oncogenic Ras-induced degradation of p27Kip1. These results suggest that the loss of substrate attachment induces the cell cycle arrest through the up-regulation of p27Kip1 mRNA, but the oncogenic Ras confers anchorage independence by accelerating p27Kip1 degradation through the activation of the MAP kinase signaling pathway. Furthermore, we have found that p27Kip1 is phosphorylated by MAP kinase in vitro and the phosphorylated p27Kip1 cannot bind to and inhibit cdk2.

Amino Acid Sequence↗
PubMed1997

Inhibition of anchorage-independent growth of ras-transformed cells on polyHEMA surface by antisense oligodeoxynucleotides directed against K-ras.

We examined the effect of antisense oligodeoxynucleotides (AS ODNs) directed against v-Ki-ras on the anchorage-independent growth of v-Ki-ras-transformed rat fibroblasts using plates coated with an antiadhesive polymer, poly(2-hydroxyethyl methacrylate) (polyHEMA). Among AS ODNs tested, 17mer AS ODN centered around codon 12 of v-Ki-ras inhibited the v-Ki-Ras expression and v-Ki-Ras-induced anchorage-independent growth, while its sense sequence did not affect it. Using polyHEMA plates, the direct addition of AS ODNs to the cells growing anchorage-independently and various treatment schedules of AS ODNs are now available to identify the most desirable conditions for AS ODNs treatment.

Animals↗