Biomedical subjects

T Natsume

Publications and source records attributed to T Natsume.

At least 19 recordsLinked to original sources

PubMed2006

Reference profiling of the genomic response induced by an antimicrotubule agent, TZT-1027 (Soblidotin), in vitro.

TZT-1027 is an antimicrotubule agent targeting beta-tubulin that is undergoing clinical development. The genomic response of cancer cells to TZT-1027 was profiled to evaluate its biochemical activity. A lung cancer cell line, PC-14, was exposed to antimicrotubule agents including dolastatins, Vinca alkaloids and taxanes at an equivalent toxicity level. Alterations in the TZT-1027-induced gene expression of approximately 600 genes were then examined using microarray technology and the resulting gene profiles were compared with those for cells exposed to the other antimicrotubule agents. A principle component analysis using the whole gene set demonstrated that TZT-1027 produced similar gene profiles to those produced by dolastatin 10, but that these gene profiles differed from those produced by other agents. The agents were classified according to their induced genomic response in a molecular structure-dependent manner. Genes whose expression profiles differed according to drug class included intermediate filaments, extracellular matrix protein and Rho regulatory genes that may be involved in cytoskeletal and angiogenesis processes that are regulated by microtubule dynamics. TZT-1027 produces a unique genomic response profile distinct from that of Vinca alkaloids and taxanes, suggesting that this agent has a different mechanism of action. The selected genes may act as pharmacodynamic biomarkers allowing the unique mode of action of TZT-1027 to be discriminated from those of other antimicrotubule agents.

Antineoplastic Agents↗

PubMed2005

Investigation of a Kubo-formula-based approach to estimate DNA conductance in an atomistic model.

A novel approach to estimate DNA conductance based upon Kubo formula is presented and discussed. Using this approach, the effects of base pair mismatches, different conformational changes and base pair sequence on DNA electrical properties were investigated. The results were compared with the data from other methods. The new approach makes possible very fast estimation of conductance spectra for oligonucleotides with hundreds of base pairs and can easily be extended to treat arbitrary chemical modifications of DNA.

Base Pair Mismatch↗

PubMed2001

Association of p53 gene mutations with sensitivity to TZT-1027 in patients with clinical lung and renal carcinoma.

BACKGROUND: It has been revealed that chemotherapy using DNA-damaging agents and radiotherapy were influenced by the p53 status of tumors; however, p53 status did not influence chemotherapy using antimicrotubule agents. To elucidate whether a novel antimicrotubule agent, TZT-1027, is influenced by the p53 status of tumors, the authors investigated the sensitivities of specimens obtained from patients with nonsmall cell lung carcinoma (NSCLC) and renal cell carcinoma (RCC) to various anticancer agents, including TZT-1027, and the status of the p53 gene in those specimens. METHODS: Twenty-nine NSCLC specimens and 22 RCC specimens were analyzed for their sensitivity to various anticancer agents and their p53 status. Sensitivities of the specimens to nine anticancer agents were determined by flow cytometric analysis. To determine p53 status, polymerase chain reaction amplification with primers for exons 5--9 was conducted, and the products were subjected to single-strand conformation polymorphism analysis. RESULTS: In the NSCLC specimens, anticancer agents, including TZT-1027, showed strong antitumor activity against 50--75% of specimens with the wild type p53 gene. TZT-1027 showed strong antitumor activity against 40% of specimens with the mutant type p53 gene, whereas DNA-damaging agents showed such activity only in 16--28% of specimens. In RCC specimens, TZT-1027 showed potent antitumor activity in 29% of specimens with the wild type gene, and DNA-damaging agents showed such activity in 6--18% of specimens. TZT-1027 showed strong antitumor activity in 40% of specimens with the mutant type p53 gene, whereas DNA-damaging agents showed such activity only in 0--20% of specimens. CONCLUSIONS: We found evidence to suggest that TZT-1027 was influenced less by the p53 status of specimens than DNA-damaging agents. Therefore, TZT-1027 is expected to show similar antitumor activity against tumors with a loss of p53 function as well as those with normal function of p53 in clinical fields.

Aged↗

PubMed2001

BIA-MS-MS: biomolecular interaction analysis for functional proteomics.

One of the experimental processes of functional proteomics is the analysis of protein interaction. Here, we review a new analytical platform, BIA-MS, for protein interaction analysis. BIA-MS is an integration of a surface plasmon resonance biosensor for real-time interaction analysis and mass spectrometry for the subsequent identification of interacting molecules.

Biosensing Techniques↗

PubMed2001

Gene expression profiling of exposure to TZT-1027, a novel microtubule-interfering agent, in non-small cell lung cancer PC-14 cells and astrocytes.

Clinical use of TZT-1027, a microtubule-interfering agent that inhibits the polymerization of tubulin, is expected because of its potent effects on solid tumors. TZT-1027 is thought to act directly on cellular microtubules, and arrest cell mitosis, however, the molecular mechanisms of the microtubule damage by TZT-1027 have not been fully identified. To investigate the possible novel mechanisms of action of TZT-1027, we used the cDNA macroarray technique to examine its effect on the expression of hundreds of tightly transcriptionally controlled genes. We used two cell lines, one was human non-small cell lung carcinoma PC-14 cells as a model for cancer cells, and the other was human astrocytes as a model for normal neuronal cells, because the dose-limiting-factor of microtubule-interfering agents is mainly peripheral neurotoxicity. mRNAs prepared from the PC-14 and astrocyte cell lines treated with TZT-1027 were compared with 588 genes spotted onto the filter, and which gene groups TZT-1027 modulated between the two cell lines was investigated. TZT-1027 exposure modulated expression of a variety of genes including the genes encoding cell-cycle and growth regulators, receptors, angiogenesis and invasion regulators, rho family small GTPases and their regulators and growth factors and cytokines. However, the way of gene regulation by TZT-1027 exposure was different between PC-14 cells and astrocytes. Genes up-regulated in both PC-14 cells and astrocytes were those for RAR-epsilon, TNFR 1 and 2 and so on. Specifically altered genes in PC-14 cells, such as the genes coding for cytokeratin 8, XPG, fau and the genes regulated only in PC-14 cells may be involved in the antitumor activity of TZT-1027. On the other hand, growth factor receptor precursors was upregulated specifically in astrocytes by TZT-1027 and this gene regulation only in astrocytes may be candidates related with neurotoxicity.

Antineoplastic Agents↗

PubMed2001

The cells of the rabbit meniscus: their arrangement, interrelationship, morphological variations and cytoarchitecture.

Four major morphologically distinct classes of cells were identified within the adult rabbit meniscus using antibodies to cytoskeletal proteins. Two classes of cell were present in the fibrocartilage region of the meniscus. These meniscal cells exhibited long cellular processes that extended from the cell body. A third cell type found in the inner hyaline-like region of the meniscus had a rounded form and lacked projections. A fourth cell type with a fusiform shape and no cytoplasmic projections was found along the superficial regions of the meniscus. Using a monoclonal antibody to connexin 43, numerous gap junctions were observed in the fibrocartilage region, whereas none were seen in cells either from the hyaline-like or the superficial zones of the meniscus. The majority of the cells within the meniscus exhibited other specific features such as primary cilia and 2 centrosomes. The placement of the meniscal cell subtypes as well as their morphology and architecture support the supposition that their specific characteristics underlie the ability of the meniscus to respond to different types of environmental mechanical loads.

Animals↗

PubMed2000

Molecular cloning and expression profile of Xenopus calcineurin A subunit(1).

We have cloned a cDNA encoding a catalytic subunit of calcineurin (CnA) expressed in Xenopus oocytes. The deduced amino acid sequence indicates 96.3% and 96.8% identities with the mouse and human CnAalpha isoforms, respectively. Xenopus CnA (XCnA) RNA and protein are expressed as maternal and throughout development. Recombinant XCnA protein interacted with calmodulin in the presence of Ca(2+). Deletion of calmodulin binding domain and auto-inhibitory domain revealed calcium independent phosphatase activity, thereby showing that XCnA is likely to be modulated by both calmodulin and calcium.

Amino Acid Sequence↗

PubMed2000

Combination of biomolecular interaction analysis and mass spectrometric amino acid sequencing.

We describe an approach for the combination of biomolecular interaction analysis (BIA) and electrospray tandem mass spectrometry (ESI/MS/MS) to obtain sequence information on the affinity-bound proteins on the sensor chip of BIA. The procedure is illustrated with stable and unstable interactions of recombinant proteins, i.e., histidine-tagged protein-Ni2+/NTA and 1,4,5-inositol trisphosphate receptor-ligand interactions. The E. coli lysates expressing the recombinant proteins were passed through the sensor chips, and biomolecular interactions were monitored in real time. The molecules detected on the sensor chip were digested by delivering proteolytic enzyme to the sensing flow cells. The resulting on-chip digested peptide mixture at the mid- to low-femtomole level was recovered on a microcapillary reversed-phase precolumn by an on-line system and analyzed using HPLC-MS/MS. In both cases, unambiguous sequence information on the recombinant proteins isolated on the sensor chip was obtained from only a single run of analysis. The combined BIA-MS/MS may prove to be a general and versatile system to discover novel biomolecular interactions and to analyze protein complexes.

Calcium Channels↗

PubMed2000

Identification of the ligand-binding site of the BMP type IA receptor for BMP-4.

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta (TGF-beta) superfamily of multifunctional cytokines. BMP induces its signal to regulate growth, differentiation, and apoptosis of various cells upon trimeric complex formation with two distinct type I and type II receptors on the cell surface: both are single-transmembrane serine/threonine kinase receptors. To identify the amino acid residues on BMP type I receptor responsible for its ligand binding, the structure-activity relationship of the extracellular ligand-binding domain of the BMP type IA receptor (sBMPR-IA) was investigated by alanine-scanning mutagenesis. The mutant receptors, as well as sBMPR-IA, were expressed as fusion proteins with thioredoxin in Escherichia coli, and purified using reverse phase high performance liquid chromatography (RP-HPLC) after digestion with enterokinase. Structural analysis of the parent protein and representative mutants in solution by CD showed no detectable differences in their folding structures. The binding affinity of the mutants to BMP-4 was determined by surface plasmon resonance biosensor. All the mutant receptors examined, with the exception of Y70A, displayed reduced affinities to BMP-4 with the rank order of decreases: I52A (17-fold) approximately F75A (15-fold) >> T64A (4-fold) = T62A (4-fold) approximately E54A (3-fold). The decreases in binding affinity observed for the latter three mutants are mainly due to decreased association rate constants while alterations in rate constants both, for association and dissociation, result in the drastically reduced affinities for the former two mutants. These results allow us to conclude that sBMPR-IA recognizes the ligand using the concave face of the molecule. The major ligand-binding site of the BMP type IA receptor consists of Phe75 in loop 2 and Ile52, Glu54, Thr62 and Thr64 on the three-stranded beta-sheet. These findings should provide a general basis for the ligand/type I receptor recognition in the TGF-beta superfamily.

Amino Acids↗

PubMed2000

Induction of apoptosis in human cancer cells by TZT-1027, an antimicrotubule agent.

TZT-1027, a newly synthesized dolastatin 10 derivative, is a potent antitumor agent which inhibits microtubule polymerization and perturbs microtubule dynamics. In this report, we investigated whether TZT-1027 inhibited the growth of various human cancer cells, and the cell death caused by TZT-1027 was due to apoptosis. In addition, we elucidated the apoptosis machinery induced by treatment with TZT-1027. The 50% growth-inhibitory concentrations (IC50 values) of TZT-1027 on cancer cells derived from various sources were not more than 5.9 ng/ml. TZT-1027 showed superior cytotoxicity than any other antitumor agents. Next, we evaluated morphological nuclear change, namely, chromatin condensation and DNA fragmentation. We used three cancer cell lines derived from different types in view of having apoptosis related protein, human leukemia HL-60 (in the presence of both Caspase-3 and Bcl-2), human breast cancer MCF-7 (in the absence of Caspase-3), and human prostate cancer DU145 (in the absence of Bcl-2). TZT-1027 induced DNA fragmentation in the presence but not absence of Caspase-3. Nevertheless, apoptic chromatin condensation was observed in all cancer cells even if there was no Caspase-3. Furthermore, we examined whether TZT-1027, microtubule-disrupting agent, influenced cell cycle progression. Flow cytometric analysis revealed the cells treated with TZT-1027, and with the other antimicrotubule agents, to be arrested at the G2/M phase and subsequently to show fragmented DNA smaller than that of G1 phase cells. Moreover, we tested TZT-1027 for its ability to induce Bcl-2 phosphorylation in human cancer cell lines. TZT-1027 and other agents which interacted with microtubules induced Bcl-2 phosphorylation, whereas DNA-damaging agents did not. The present results suggested an association of the growth-inhibitory effect of TZT-1027 with the induction of apoptosis and indicated that the apoptosis induced by TZT-1027 was followed by G2/M arrest even if there was no Caspase-3 or Bcl-2.

Antineoplastic Agents↗

PubMed2000

Characterization of the interaction of TZT-1027, a potent antitumor agent, with tubulin.

TZT-1027, a derivative of dolastatin 10 isolated from the Indian Ocean sea hare Dolabella auricularia in 1987 by Pettit et al., is a potent antimicrotubule agent. We have compared the activity of TZT-1027 with that of dolastatin 10 as well as the vinca alkaloids vinblastine (VLB), vincristine (VCR) and vindesine (VDS). TZT-1027 and dolastatin 10 inhibited microtubule polymerization concentration-dependently at 1 - 100 microM with IC50 values of 2.2 +/- 0.6 and 2.3 +/- 0.7 microM, respectively. VLB, VCR and VDS inhibited microtubule polymerization at 1 - 3 microM with IC50 values of 2.7 +/- 0.6, 1.6 +/- 0.4 and 1.6 +/- 0.2 microM, respectively, but showed a slight decrease in inhibitory effect at concentrations of 10 microM or more. TZT-1027 also inhibited monosodium glutamate-induced tubulin polymerization concentration-dependently at 0.3 - 10 microM, with an IC50 of 1.2 microM, whereas VLB was only effective at 0.3 - 3 microM, with an IC50 of 0.6 microM, and caused so-called "aggregation" of tubulin at 10 microM. Scatchard analysis of the binding data for [(3)H]VLB suggested one binding site (Kd 0.2 +/- 0.04 microM and Bmax 6.0 +/- 0.26 nM / mg protein), while that for [(3)H]TZT-1027 suggested two binding sites, one of high affinity (Kd 0.2 +/- 0.01 microM and Bmax 1.7 +/- 0.012 nM / mg protein) and the other of low affinity (Kd 10. 3 +/- 1.46 microM and Bmax 11.6 +/- 0.83 nM / mg protein). [(3)H]TZT-1027 was completely displaced by dolastatin 10 but only incompletely by VLB. [(3)H]VLB was completely displaced by dolastatin 10 and TZT-1027. Furthermore, TZT-1027 prevented [(3)H]VLB from binding to tubulin in a non-competitive manner according to Lineweaver-Burk analysis. TZT-1027 concentration-dependently inhibited both [(3)H]guanosine 5'-triphosphate (GTP) binding to and GTP hydrolysis on tubulin. VLB inhibited the hydrolysis of GTP on tubulin concentration-dependently to a lesser extent than TZT-1027, but no inhibitory effect of VLB on [(3)H]GTP binding to tubulin was evident even at 100 microM. Thus, TZT-1027 affected the binding of VLB to tubulin, but its binding site was not completely identical to that of VLB. TZT-1027 had a potent inhibitory effect on tubulin polymerization and differed from vinca alkaloids in its mode of action against tubulin polymerization.

Animals↗

PubMed2000

TZT-1027, an antimicrotubule agent, attacks tumor vasculature and induces tumor cell death.

TZT-1027, a dolastatin 10 derivative, is an antimicrotubule agent with potent antitumor activity both in vitro and in vivo. In this study, we performed biochemical and histopathological examinations, and evaluated TZT-1027-induced tumoral vascular collapse and tumor cell death in an advanced tumor model, murine colon 26 adenocarcinoma. In addition, we studied the effects of TZT-1027 on cultured human umbilical vein endothelial cells (HUVEC). Tolerable doses of TZT-1027 induced tumor-selective hemorrhage within 1 h. This hemorrhage occurred mainly in the peripheral area of the tumor mass. Measurements of tumoral hemoglobin content and dye permeation revealed that the hemorrhage occurred firstly and tumor blood flow stopped secondarily. The vascular damage was followed by continuous induction of apoptosis of the tumor cells, tumor tissue necrosis, and tumor regression. In cultured HUVEC, TZT-1027 induced marked cell contraction with membrane blebbing in 30 min. These cell changes were completely inhibited by K252a, a broad-spectrum inhibitor of protein kinases. These effects of TZT-1027 on both tumor vasculature and HUVEC were greater than those of vincristine. In conclusion, TZT-1027 quickly attacked the well-developed vascular system of advanced tumors by a putative protein kinase-dependent mechanism, and then blocked tumor blood flow. Therefore, TZT-1027 has both a conventional antitumor activity and a unique anti-tumoral vascular activity, making it a potentially powerful tool for clinical cancer therapy.

Animals↗

PubMed2000

Anatomy of the right anterosuperior area (segment 8) of the liver: evaluation with helical CT during arterial portography.

PURPOSE: To evaluate the segmental anatomy of the right anterosuperior area (segment 8) of the liver by using helical computed tomography during arterial portography (CTAP). MATERIALS AND METHODS: Twenty-seven patients without lesions at segment 8 underwent helical CTAP. Three-dimensional portograms were reconstructed to verify the course of the portal veins. The number of subsegmental branches, in addition to the branching point and the distribution in segment 8, was assessed. RESULTS: In 25 (93%) patients, the dorsal branch of segment 8 gave rise to dorsally directed branches posterior to the right hepatic vein. In only four (25%) of 16 patients in whom the medial branch of segment 8 arose near the porta hepatis, the long paracaval portal branch of the caudate lobe extended upward above the interval between the middle and right hepatic veins. CONCLUSION: In most of the patients, the dorsal branches of segment 8 supplied the dorsocranial area of the right lobe posterior to the right hepatic vein. The paracaval portion of the caudate lobe was limited to below the interval between the middle and right hepatic veins in the majority of patients who showed medial branches of segment 8 arising near the porta hepatis. Recognition of this vascular anatomy is clinically important for preoperative evaluation of hepatic tumors in segment 8 because it may contribute to a safer surgical approach.

Adult↗

PubMed2000

[Clinical significance of serum p53 antibody detection in a chemosensitivity assay in cases of human colorectal cancer].

Alteration of the p53 gene product occurs frequently during the progression of colorectal cancer. Recently, mutated p53 protein was found to induce the production of anti-p53 antibodies in the serum of patients. The purpose of this study was to evaluate the relationship between p53 status in serum and chemosensitivity in resectable colorectal cancer patients. A total of 35 patients with primary colorectal cancer who underwent surgical treatment were examined by chemosensitivity test with the viable tumor samples using Histoculture Drug Response Assay (HDRA). Serum samples of these patients to test for p53 antibodies were obtained before tumor resection, and assayed in duplicate by using an enzyme-linked immunosorbent assay (ELISA) kit. The inhibition index of 5-FU and CDDP, determined by the HDRA method, in the sero-positive group was significantly lower than that of the sero-negative group (p < 0.01). Furthermore, significant statistical differences in chemosensitivity to 5-FU and CDDP were revealed depending on the presence of serum p53 antibodies. There was no relationship between chemosensitivity assay and tumor marker positivity or clinicopathological features in these patients. Detection of serum p53 antibodies, which reflects p53 mutations in tumor tissue, is a simple method which correlates with chemosensitivity, and may contribute to the selection of favorable chemotherapeutic strategies of colorectal cancer.

Antineoplastic Agents↗

PubMed1999

Stimulus-coupled interaction of tyrosine hydroxylase with 14-3-3 proteins.

Tyrosine hydroxylase (TH) is phosphorylated by CaM kinase II and is activated in situ in response to a variety of stimuli that increase intracellular Ca(2+). We report here, using baculovirus-expressed TH, that the 14-3-3 protein binds and activates the expressed TH when the enzyme is phosphorylated at Ser-19, a site of CaM kinase II-dependent phosphorylation located in the regulatory domain of TH. Site-directed mutagenesis showed that a TH mutant in which Ser-19 was substituted by Ala retained enzymatic activity at the same level as the non-mutated enzyme, but was a poor substrate for CaM kinase II and did not bind the 14-3-3 protein. Likewise, a synthetic phosphopeptide (FRRAVpSELDA) corresponding to the part of the TH sequence, including phosphoSer-19, inhibited the interaction between the expressed TH and 14-3-3, while the phosphopeptide (GRRQpSLIED) corresponding to the site of cAMP-dependent phosphorylation (Ser-40) had little effect on complex formation. The complex was very stable with a dissociation constant of 3 nM. Furthermore, analysis of PC12nnr5 cells transfected with myc-tagged 14-3-3 showed that 14-3-3 formed a complex with endogenous TH when the cultured cells were exposed to a high K(+) concentration that increases intracellular Ca(2+) and phosphorylation of Ser-19 in TH. These findings suggest that the 14-3-3 protein participates in the stimulus-coupled regulation of catecholamine synthesis that occurs in response to depolarization-evoked, Ca(2+)-dependent phosphorylation of TH.

14-3-3 Proteins↗

PubMed1999

Calmodulin inhibits inositol 1,4,5-trisphosphate-induced calcium release through the purified and reconstituted inositol 1,4,5-trisphosphate receptor type 1.

Our previous studies have demonstrated that calmodulin binds to IP3R type I (IP3R1) in a Ca2+ dependent manner, which suggests that calmodulin regulates the IP3R1 channel. In the present study, we investigated real-time kinetics of interactions between calmodulin and IP3R1 as well as effects of calmodulin on IP3-induced Ca2+ release by purified and reconstituted IP3R1. Kinetic analysis revealed that calmodulin binds to IP3R1 in a Ca2+ dependent manner and that both association and dissociation phase consist of two components with time constants of k(a) = 4.46 x 10(2) and > 10(4) M(-1) s(-1) k(d) = 1.44 x 10(-2) and 1.17 x 10(-1) s(-1). The apparent dissociation constant was calculated to be 27.3 microM. The IP3-induced Ca2+ release through the purified and reconstituted IP3R1 was inhibited by Ca2+/calmodulin, in a dose dependent manner. We interpret our findings to mean that calmodulin binds to IP3R1 in a Ca2+ dependent manner to exert inhibitory effect on IP3R channel activity. This event may be one of the mechanisms governing the negative feedback regulation of IP3-induced Ca2+ release by Ca2+.

Animals↗

PubMed1999

Real time analysis of interaction between inositol 1,4, 5-trisphosphate receptor type I and its ligand.

Inositol 1,4,5-trisphosphate (IP(3)) is an important second messenger that releases intracellular Ca(2+) by binding to its specific receptor, inositol 1,4,5-trisphosphate receptor (IP(3)R), in a wide range of cellular processes. We report here large-scale expression and purification of N-terminal 604 amino acids of IP(3)R type 1 (T604) expressed in E. coli, which contains the ligand binding domain. Surface plasmon resonance biosensor studies showed that purified T604 could bind to its ligands with binding specificity identical to that of full-length native IP(3)R type 1. Kinetic parameters of T604 for IP(3) consisted of a fast association rate constant (K(ass) = 1.2 x 10(6) M(-1) s(-1)) and a rapid dissociation rate constant (k(diss) = 1 s(-1)), and the equilibrium dissociation constant was determined to be 336 nM, at 150 mM NaCl and pH 7.4. However, association and dissociation patterns depended on the pH level and ionic strength. These results pave the way toward detail analysis of structure-function analysis of the ligand binding domain of IP(3)R type 1 for its ligands.

Amino Acid Sequence↗

PubMed1999

[Activity of a novel antitumor agent, TZT-1027].

We studied the antitumor activity of newly synthesized dolastatin 10 analogs. TZT-1027 showed remarkable activity and was selected for further development. TZT-1027 was found to inhibit the assembly of porcine brain microtubule proteins and to depolymerize the polymerized microtubule proteins. Therefore, its mechanism of antitumor activity seems to be at least partially ascribed to the inhibition of microtubule assembly. We further studied the binding site of TZT-1027 on tubulin. Scatchard analysis of 3H-TZT-1027 binding data suggested two binding sites including a high affinity site and a low affinity site. TZT-1027 affected the binding of vinblastine (VBL) on tubulin but its binding site isn't identical to the VBL binding site. TZT-1027 induced apoptosis within 24 h, not only in human leukemia cells such as HL-60, but also in solid tumors such as human prostate carcinoma cells DU145 and human mammary carcinoma cells MCF-7. TZT-1027 showed good antitumor activity against human xenografts (MX-1 and LX-1) without causing serious body weight reduction, which resulted in tumor regression. We examined the effect of TZT-1027 on the established tumor vasculature using the dye perfusion into tumor. TZT-1027 exhibited considerable antivascular activity in tumor sections in addition to excellent cytotoxic effect.

Animals↗