Biomedical subjects

J Ding

Publications and source records attributed to J Ding.

At least 109 records · Page 6Linked to original sources

PubMed2000

Candidate multi-epitope vaccines in aluminium adjuvant induce high levels of antibodies with predefined multi-epitope specificity against HIV-1.

Some neutralizing epitopes on HIV-1 envelope proteins were identified to induce antibodies which could effectively inhibit the infection of different strains in vitro. But only very low levels of these antibodies were determined in the HIV-1 infected individuals. To increase the levels of protective antibodies in vivo, we suggested multi-epitope vaccine as a new strategy to induce high level of neutralization antibodies with predefined multi-epitope specificity. A synthesized epitope peptide MP (CG-GPGRAFY-G-ELDKWA-G-RILAVERYLKD) containing three neutralizing epitopes (GPGRAFY, ELDKWA, RILAVERYLKD) was conjugated to carrier protein KLH, and then used for immunization in mouse together with aluminium adjuvant or Freund's adjuvant (FA). The candidate MP-KLH multi-epitope vaccine in aluminium adjuvant could induce antibody response very strongly to the epitope peptide C-(RILAVERYLKD-G)2 and the immunosuppressive peptide (P1) (LQARILAVERYLKDQQL) (antibody titer: 1:51200), strongly to the epitope peptide C-(ELDKWA-G)4 and the C-domain peptide (P2) (1:12800), and moderately to the epitope peptide C-(GPGRAFY)4 and the V3 loop peptide (1:1600). The immunoblotting analysis demonstrated that the antibodies in sera could recognize P1, P2, V3 loop peptides and rsgp41 (aa 539-684). These results are similar with that in the case of PI-BSA in FA, and suggest that the multi-epitope vaccine in aluminium could induce high levels of antibodies of predefined multi-epitope specificity, which provides experimental evidence for the new strategy to develop an effective neutralizing antibody-based multi-epitope vaccine against HIV-1.

AIDS Vaccines↗

PubMed2000

A novel PF/PN motif inhibits nuclear localization and DNA binding activity of the ESX1 homeoprotein.

Despite their significance for mammalian embryogenesis, the molecular mechanisms that regulate placental growth and development have not been well defined. The Esx1 homeobox gene is of particular interest because it is among the few regulatory genes that have specific expression and function in the placenta during murine development. In addition, the ESX1 protein contains several notable features that are not often associated with homeoproteins, including an atypical homeodomain of the paired-like class, a proline-rich region that contains an SH3 binding motif, and a novel repeat region consisting of prolines alternating with phenylalanines or asparagines that we term the PF/PN motif. We have found that the ESX1 protein is expressed in the labyrinth layer of the placenta in vivo, where its subcellular localization is primarily cytoplasmic. Our results suggest that this unexpected subcellular localization is conferred by the PF/PN motif, which inhibits nuclear localization of ESX1 in cell culture, as well as its DNA binding activity in vitro. Finally, we show that the proline-rich region of ESX1 mediates interactions in vitro with the c-abl SH3 domain as well as with certain WW domains. We propose that the PF/PN motif provides a novel mechanism for regulating nuclear entry and that the essential function of ESX1 during placental development is mediated by its ability to couple cytoplasmic signal transduction events with transcriptional regulation in the nucleus.

Alternative Splicing↗

PubMed2000

Development of a mathematical model that predicts optimal muscle activation patterns by using brief trains.

Because muscles must be repetitively activated during functional electrical stimulation, it is desirable to identify the stimulation pattern that produces the most force. Previous experimental work has shown that the optimal pattern contains an initial high-frequency burst of pulses (i.e., an initial doublet or triplet) followed by a low, constant-frequency portion. Pattern optimization is particularly challenging, because a muscle's contractile characteristics and, therefore, the optimal pattern change under different physiological conditions and are different for each person. This work describes the continued development and testing of a mathematical model that predicts isometric forces from fresh and fatigued muscles in response to brief trains of electrical pulses. By use of this model and an optimization algorithm, stimulation patterns that produced maximum forces from each subject were identified.

Algorithms↗

PubMed2000

A predictive model of fatigue in human skeletal muscles.

Fatigue is a major limitation to the clinical application of functional electrical stimulation. The activation pattern used during electrical stimulation affects force and fatigue. Identifying the activation pattern that produces the greatest force and least fatigue for each patient is, therefore, of great importance. Mathematical models that predict muscle forces and fatigue produced by a wide range of stimulation patterns would facilitate the search for optimal patterns. Previously, we developed a mathematical isometric force model that successfully identified the stimulation patterns that produced the greatest forces from healthy subjects under nonfatigue and fatigue conditions. The present study introduces a four-parameter fatigue model, coupled with the force model that predicts the fatigue induced by different stimulation patterns on different days during isometric contractions. This fatigue model accounted for 90% of the variability in forces produced by different fatigue tests. The predicted forces at the end of fatigue testing differed from those observed by only 9%. This model demonstrates the potential for predicting muscle fatigue in response to a wide range of stimulation patterns.

Electric Stimulation↗

PubMed2000

Immunogenicity of neutralizing epitopes on multiple-epitope vaccines against HIV-1.

Based on our hypothesis that epitope vaccine may be a new strategy to induce high levels of neutralization antibodies against HIV-1, we prepared multiple-epitope vaccines using three neutralizing epitopes (GPGRAFY, RILAVERYLKD and ELDKWA) of HIV-1 gp160, and characterized their immunogenicity. Peptide 1 [C-G-(ELDKWA-GPGRAFY)(2)-K] and peptide 2 (CG-GPGRAFY-ELDKWA-G-RILAVERYLKD) were synthesized and conjugated with carrier protein bovine serum albumin (BSA). After vaccination antibody responses to these immunogens were induced and evaluated by ELISA. The C-G-(ELDKWA-GPGRAFY)(2)-K-BSA (BSA: carrier protein) multiple-epitope vaccine induced a strong antibody response to the C-G-(ELDKWA-GPGRAFY)(2)-K peptide (antibody titer: 1:25,600) and C-(ELDKWAG)(4) peptide (antibody titer: 1:12,800), but a weak antibody response to the C-(GPCGRAFY)(4) peptide. The CG-GPGRAFY-ELDKWA-G-RILAVERYLKD-K-BSA (BSA: carrier protein) multiple-epitope vaccine also induced strong antibody response to the CG-GPGRAFY-ELDKWA-G-RILAVERYLKD-K peptide (antibody titer: 1:25, 600) and C-(ELLDKWAG)(4) peptide (antibody titer: 1:6,400), a very strong response to C-(RIVALVERYLKD-G)(2)-K peptide (dilution: 1:102, 400), and a very weak response to the C-(GPGRAFY)(4) peptide (dilution: 1:400) in mice. Both antisera induced by both multiple-epitope vaccines interacted with the recombinant soluble gp41 (rgp41), but did not bind two control peptides. In comparison with both epitope vaccines, the rgp160 subunit vaccine could induce weak epitope-specific antibody response to these three epitopes on the three epitope peptides and V3, N-domain and C-domain peptides (dilution: 1:400-1:1,600). These results indicate that both multiple-epitope vaccines could induce high levels of antibodies to both neutralizing epitopes RILAVERYLKD and ELDKWA, while the GPGRAFY epitope on both vaccines appeared to have weak immunogenicity. Both multiple-epitope vaccines showed significant potency on inducing high levels of epitope-specific neutralization antibodies in comparison with rgp160 subunit vaccine.

AIDS Vaccines↗

PubMed2000

Preventing endotoxin-stimulated alveolar macrophages from decreasing epithelium Na+ channel (ENaC) mRNA levels and activity.

The acute respiratory distress syndrome is characterized by impairment of the alveolar-capillary barrier. Our laboratory has shown that distal lung epithelial cell (DLEC) amiloride-sensitive Na+ transport is impaired by in vitro coculture with endotoxin (lipopolysaccharide)-stimulated alveolar macrophages (AM) through an L-arginine-dependent mechanism. To investigate the effect of this model on mRNA levels of the rat epithelial Na+ channel, mature fetal rat DLEC monolayers were incubated for 16 h with rat AM (1 x 10(7)) and lipopolysaccharide (10 microg/mL), or the cell-free supernatant of lipopolysaccharide-stimulated rat AM. Such exposure resulted in a profound decrease in mRNA expression for all subunits (alpha, beta, and gamma) of the rat epithelial Na+ channel, without affecting 18S RNA levels. This effect was prevented by the antioxidant N-acetylcysteine. In separate experiments, confluent DLEC monolayers were exposed to lipopolysaccharide-stimulated AM supernatant for 16 h with or without N-acetylcysteine and DTT and studied in Ussing chambers. As previously demonstrated in our laboratory, AM supernatant resulted in a significant (p < 0.05) impairment of DLEC Na+ transport, as reflected by a decrease in the amiloride-sensitive component of short-circuit current (control, 3.96 +/- 0.18 microA/cm2 versus supernatant, 2.34 +/- 0.56 microA/cm2; p < 0.05). This effect was significantly reversed by N-acetylcysteine (3.55 +/- 0.48 microA/cm2), but not by DTT (1.87 +/- 0.21 microA/cm2). N-acetylcysteine, but not DTT, increased DLEC thiol levels. These studies elucidate mechanisms by which activated AM impair alveolar epithelial barrier function in an in vitro model of acute lung injury.

Animals↗

PubMed2000

Cardiac pacing in heart failure patients with left bundle branch block: impact of pacing site for optimizing left ventricular resynchronization.

BACKGROUND: Acute left ventricular pacing has been associated with hemodynamic improvement in patients with congestive heart failure and wide QRS complex. We hypothesized that pacing two left ventricular sites simultaneously would produce faster activation and better systolic function than single-site pacing. METHODS: We selected 14 heart failure patients (NYHA functional class III or IV) in normal sinus rhythm with left bundle branch block and QRS > 150 ms. An 8F dual micromanometer catheter was placed in the aorta for measuring +dP/dt (mmHg/s), aortic pulse pressure (mmHg), and end-diastolic pressure (mmHg). Pacing leads were positioned via coronary veins at the posterior base and lateral wall. Patients were acutely paced VDD at the posterior base, lateral wall, and both sites (dual-site) with 5 atrioventricular delays (from 8 ms to PR -30 ms). Pacing sequences were executed in randomized order using a custom external computer (FlexStim, Guidant CRM). RESULTS: Dual-site pacing increased peak +dP/dt significantly more than posterior base and lateral wall pacing. Dual-site and posterior base pacing raised aortic pulse pressure significantly more than lateral wall pacing. Dual-site pacing shortened QRS duration by 22 %, whereas posterior base and lateral wall pacing increased it by 2 and 12%, respectively (p = 0.006). CONCLUSIONS: In heart failure patients with left bundle branch block, dual-site pacing improves systolic function more than single-site stimulation. Improved ventricular activation synchrony, expressed by paced QRS narrowing, may account for the additional benefit of dual- vs single-site pacing in enhancing contractility. This novel approach deserves consideration for future heart failure pacing studies.

Adult↗

PubMed2000

Regulation of telomerase activity in camptothecin-induced apoptosis of human leukemia HL-60 cells.

AIM: To explore the regulation of telomerase activity in camptothecin induced apoptosis of human leukemia HL-60 cells. METHODS: Apoptosis of HL-60 cells was induced by camptothecin (1 mg/L) for 2, 4, and 6 h. Apoptosis was determined by agarose electrophoresis and flow cytometry analysis. To assess telomerase activity, a PCR-based telomeric repeat amplification protocol assay (TRAP) was used. RT-PCR was performed to examine the mRNA levels of hTR (human telomerase RNA component), hEST2/hTERT (human telomerase reverse transcriptase), TLP1/TP1 (telomerase association protein 1), and bcl-2 (B cell leukemia/lymphoma 2 gene) in HL-60 cells before and after camptothecin treatment. RESULTS: Telomerase activity was decreased in a time-dependent manner during the camptothecin induced apoptosis of HL-60 cells. However, no difference in expression of each telomerase subunit was detected, while expression of bcl-2 was progressively down-regulated. CONCLUSION: These lines of evidences indicated that down-regulation of the telomerase activity in HL-60 cells was closely related to camptothecin-induced apoptosis, and the telomerase activity was not blocked at the transcriptional levels of the genes of the known ribonucleoprotein (RNP) complex components. We also found that bcl-2 did not regulate the mRNA expressions of telomerase subunits directly.

Apoptosis↗

PubMed2000

Pulmonary embolism associated with nephrotic syndrome in children: a preliminary report of 8 cases.

OBJECTIVE: To investigate the incidence, clinical features of pulmonary embolism (PE) secondary to nephrotic syndrome(NS) in Chinese children. METHODS: Pulmonary perfusion imaging (PPI) and chest radiography was performed on 20 NS patients with elevated plasma D-dimer. The patients with PE were given anticoagulative therapy with heparin and persantine. RESULTS: Among 20 NS patients, eight cases, aged from 5 to 12 years, 6 boys and 2 girls, were found to have PE. Of them 5 were primary NS and 3 were secondary NS. PPI showed an involvement of 1 pulmonary segment in 3 cases, of 2 pulmonary segments in 2, of 3 pulmonary segments in 2, and of 6 pulmonary segments in 1. Most patients did not present clinical signs and symptoms. Two weeks after the administration of intravenous heparin for anticoagulative therapy, 6 out of 8 cases showed a recovery or an improvement. CONCLUSION: The results of this study suggest that PE be not a rare complication in NS children. Most patients had no obvious clinical manifestation and their prognose was favorable if diagnosed and treated in time.

Adolescent↗

PubMed2000

[Analysis of postoperative short-term mortality after lung resection and the corresponding treatment strategies].

OBJECTIVE: To study the risk factors of postoperative short-term mortality after lung resection. METHOD: Retrospective analysis on 46 cases ongoing lung resection but died within 1 month postoperatively. RESULTS: There were 37 males and 9 females in this group, aging 38-74 years old. The mortalities be of the group > or = 60 year-old and below 60 were 1.23% and 0.45% (P < 0.01), respectively. The short-term mortalities of the group of pneumonectomy and partial lung resection were 0.51% and 0.32% (P < 0.01), respectively. Causes of the postoperative death were 17 cases of complications of circulatory system, 10 of cancer metastasis, 10 of acute respiratory failure, 6 of intestinal complications, 2 of bronchopleural fistula and 1 of renal failure. CONCLUSION: Measures such as manuver of perioperative complications and coexistant disorders appropriately, reduction of unnecessary explorative thoracotomy and palliative cancer resection, avoidence of pneumonectomy as possible may be helpful to lower the postoperative short-term mortality.

Adult↗

PubMed2000

[Analysis of influence of axial length and keratometric value on the curative effects of excimer laser photorefractive keratectomy for myopia].

OBJECTIVE: To evaluate the influence of axial length (AL) and keratometric value (KV) on the curative effects of excimer laser photorefractive keratectomy (PRK) for myopia. METHOD: A Keracor-17 excimer laser was used to treat 80 patients (121 eyes) with myopia. The cases were divided into three groups according to the AL and KV: The first group AL > 26 mm, KV 45 D, 36 eyes; the third group AL 0.05). The cases with uncorrected visual acuity >or= 0.5 had significant difference between the first and the second group and between the first and the third group (chi(2) = 6.30, P < 0.05). Multiple linear regression and correlative analysis showed that the increase in ocular axis was an unfavorable factor to visual acuity, while the increase in keratometric value was a favorable factor to visual acuity. CONCLUSION: PRK for treatment of myopia is an effective and safe refractive surgery. When the myopic degrees are identical, the postoperative outcome of myopia with increase in keratometric value as the main pathogeny is better than the myopia with increase in axial length as the main pathogeny.

Adolescent↗

PubMed2000

[Study on the relations between HLA-DRB 1 alleles and Helicobacter pylori infection].

OBJECTIVE: In order to study the relation between human leukocyte antigen (HLA) DRB1 alleles and Helicobacter pylori (Hp) infection. METHODS: Hp-IgG antibody from 46 gastric cancer (GC), 75 esophageal cancer and 100 population-based controls were identified by Hp-IgG quantitative enzyme immunoassay. Biotest HLA-DRB enzyme linked probe hybridization assay kit (low resolution) was used to identify DRB1 alleles. RESULTS: (1) Frequency of DRB1 * 08 was significantly higher in Hp-IgG positive group than in Hp-IgG negative group (13.1% vs 4.4%, chi(2) = 11.14, P < 0.001). Frequency of DRB1 * 12 was significantly lower in Hp-IgG positive group than in Hp-IgG negatives (5.4% vs 11.3%, chi(2) = 4.49, P < 0.05). (2) Frequency of DRB1 * 02 in GC was significantly higher than that of controls. Frequency of DRB1 * 07 in GC was significantly lower than that of controls. However, neither the frequency of DRB1 * 02 between Hp-IgG positive and Hp-IgG negative groups nor the frequency of DRB1 * 07 between Hp-IgG positive and Hp-IgG negative groups showed significant differences in GC and controls. CONCLUSIONS: (1) HLA-DRB1 * 08 might serve a genetic risk factor for Hp infection while DRB1 * 12 might play a role of protecting effect against Hp infection. (2) DRB1 * 02 might be a genetic risk factor for GC while DRB1 * 07 might play a role of protecting effect against GC. However, the relations between DRB1 * 02, DRB1 * 07 and GC were not associated with Hp infection.

Alleles↗

PubMed2000

[Study on simultaneous determination of multiplex trace elements in Chinese herbal medicine loulu by ICP-AES].

A method for the simultaneous determination of multiplex trace elements in Chinese herbal medicine Loulu by inductively coupled plasma atomic emission spectrometry(ICP-AES) has been presented. The operating condictions and the suitable internal standard elements were selected. The detection limits of the method are 0.005-1.24 micrograms.mL-1 for Fe, Mn, Cu, Ti, Cr, Ba, Sr, Zn, Al with relative standard deviations (RSD) of 1.20%-3.90% (n = 7). The recoveries of most elements are in the range of 90.1%-104.2%. The method proposed has been applied to the analysis of real samples and biological standard samples (GBW 08501) peach leaves. The determined values of trace elements in the biological standard sample were in good agreement with the certified values.

Asteraceae↗

PubMed1999

Insulin-like growth factor binding protein 2 is a growth inhibitory protein conserved in zebrafish.

Fish serum contains several specific binding proteins for insulin-like growth factors (IGFBPs). The structure and physiological function of these fish IGFBPs are unknown. Here we report the complete primary sequence of a zebrafish IGFBP deduced from cDNA clones isolated by library screening and rapid amplification of cDNA ends. The full-length 1,757-bp cDNA encodes a protein of 276 aa, which contains a putative 22-residue signal peptide and a 254-residue mature protein. The mature zebrafish IGFBP has a predicted molecular size of 28,440 Da and shows high sequence identity with human IGFBP-2 (52%). The sequence identities with other human IGFBPs are <37%. Chinese hamster ovary cells stably transfected with the zebrafish IGFBP-2 cDNA secreted a 31-kDa protein, which bound to IGF-I and IGF-II with high affinity, but did not bind to Des(1-3)IGF-I or insulin. Northern blot analyses revealed that the zebrafish IGFBP-2 transcript is a 1.8-kb band expressed in many embryonic and adult tissues. In adult zebrafish, IGFBP-2 mRNA levels were greatly reduced by growth hormone treatment but increased by prolonged fasting. When overexpressed or added to cultured zebrafish and mammalian cells, the zebrafish IGFBP-2 significantly inhibited IGF-I-stimulated cell proliferation and DNA synthesis. These results indicate that zebrafish IGFBP-2 is a negative growth regulator acting downstream in the growth hormone-IGF-I axis.

Amino Acid Sequence↗

PubMed1999

Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation.

Specification of the left-right (L-R) axis in the vertebrate embryo requires transfer of positional information from the node to the periphery, resulting in asymmetric gene expression in the lateral plate mesoderm. We show that this activation of L-R lateral asymmetry requires the evolutionarily conserved activity of members of the EGF-CFC family of extracellular factors. Targeted disruption of murine Cryptic results in L-R laterality defects including randomization of abdominal situs, hyposplenia, and pulmonary right isomerism, as well as randomized embryo turning and cardiac looping. Similarly, zebrafish one-eyed pinhead (oep) mutants that have been rescued partially by mRNA injection display heterotaxia, including randomization of heart looping and pancreas location. In both Cryptic and oep mutant embryos, L-R asymmetric expression of Nodal/cyclops, Lefty2/antivin, and Pitx2 does not occur in the lateral plate mesoderm, while in Cryptic mutants Lefty1 expression is absent from the prospective floor plate. Notably, L-R asymmetric expression of Nodal at the lateral edges of the node is still observed in Cryptic mutants, indicating that L-R specification has occurred in the node but not the lateral plate. Combined with the previous finding that oep is required for nodal signaling in zebrafish, we propose that a signaling pathway mediated by Nodal and EGF-CFC activities is essential for transfer of L-R positional information from the node.

Animals↗

PubMed1999

Molecular characterization of autosomal recessive chronic granulomatous disease caused by a defect of the nicotinamide adenine dinucleotide phosphate (reduced form) oxidase component p67-phox.

Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytes in which defective production of microbicidal oxidants leads to severe recurrent infections. CGD is caused by mutations in any of 4 genes encoding components of nicotinamide adenine dinucleotide phosphate (reduced form; NADPH) oxidase, the multisubunit enzyme that produces the precursor of these oxidants, superoxide. Approximately 5% of CGD patients have an autosomal recessive form of disease caused by a severe deficiency of p67-phox, a 526-amino acid subunit of the oxidase that appears to regulate electron transport within the enzyme. Here we report the biochemical and molecular characterization of 6 unrelated kindreds with p67-phox deficiency. These studies show that, as in gp91-phox and p22-phox deficiencies, the p67-phox CGD patients show a high degree of heterogeneity in the genetic defects that underlie their disease. Five different mutant alleles were identified: (1) a nonsense mutation in exon 4 (C(304) --> T); (2) a 5-nucleotide (nt) deletion in exon 13 (nts 1169-1173); (3) a splice mutation in the first nucleotide of intron 4 (G --> A); (4) a deletion of 1 nt in exon 9 (A(728)); and (5) a 9-nt in-frame deletion in exon 2 (nts 55-63). The splice mutation was seen in 3 unrelated kindreds, while the 5-nt deletion was seen in 2 apparently unrelated families (both of Palestinian origin). Homozygosity was present in 4 of the kindreds, 2 of which had consanguineous parentage. In the isolated neutrophils of each of the affected patients in the 6 kindreds, there was no measurable respiratory burst activity and no p67-phox protein detected by immunoblot analysis. The level of 67-phox mRNA was less than 10% of normal in the mononuclear leukocytes from 3 of the 4 patients analyzed by Northern blot studies. Thus, this heterogeneous group of mutations in p67-phox all lead to marked instability of mRNA or protein (or both) that results in the complete loss of NADPH oxidase activity.

Adolescent↗

PubMed1999

[Analysis of hepatitis C virus genotypes in Guizhou area, using second generation line probe assay].

OBJECTIVE: To analyse the frequency of various hepatitis C virus genotypes in different populations with HCV infection from Guizhou area. METHODS: Ninty-eight HCV isolates obtained by using RT-nested PCR from 37 patients with chronic hepatitis C (PHCs), 15 patients with hemopathy (PHs), 12 blood donors (BDs) and 34 intravenous drug-users (IVDUs) were genotyped by using the second generation line probe assay. RESULTS: Among 37 HCV isolates from PHCs, there were 34 (91.9%) genotype 1b, 3 (8.1%) mixted genotypes (1 for 1a + 1b, 1 for 1b + 2, 1 for 1a + 1b + 2a/2c, respectively). Among 15 PHs, 14 (93.3%) were type 1b, 1(6.7%) were type 1b + 2, among 12 BDs, all(100.0%) were type 1b. Among 34 IVDUs, 13(38.2%) were type 1b, 10(29.4%) were type 6a, 1(2.9%) was type 3a, 4(11.8%) were type 3b and 6(17.6%) were mixed types(2 for 1a + 2, 1 for 1a, 1b + 2, 1 for 1b + 3b, 1 for 3b + 2, 1 for 1b + 6a, respectively). CONCLUSION: The results showed that HCV subtypes 1a, 1b, 2a/2c, 3a, 3b and 6a belonging to 4 HCV genotypes(1,2,3,6) were found from different populations in Guizhou, of these, 3a, 3b and 6a were only found in IVDUs and their total frequency was above 50%.

China↗

PubMed1999

Synthesis and antitumour activity of novel diterpenequinone salvicine and the analogs.

A novel diterpenequinone named salvicine (4), structurally modified derivative of a natural product, and a series of the novel analogs have been prepared. Most of the analogs were found to be potently active against tumor cell lines in vitro. Further study on 4 in vivo demonstrated that it possessed a significant antineoplastic activity against murine S-180 Sarcoma and Lewis lung cancer, and human lung adenocarcinoma xenografts A-549 and LAX-83. The preclinical studies of 4 are now under way.

Animals↗