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Dive into the research topics where Yuji Tada is active.

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Featured researches published by Yuji Tada.


Experimental Lung Research | 2008

MURINE PULMONARY RESPONSE TO CHRONIC HYPOXIA IS STRAIN SPECIFIC

Yuji Tada; Sven Laudi; Julie Harral; Michelle Carr; Charles Ivester; Nobuhiro Tanabe; Yuichi Takiguchi; Koichiro Tatsumi; Takayuki Kuriyama; William C. Nichols; James West

Information concerning the effects of genetic variation between different background strains on hemodynamic, morphometric, and gene expression response to hypoxia would be useful. Three strains of mice were kept in hypoxia and phenotyped followed by gene profiling analysis. Among the variables examined, hematocrit, right heart muscularization, and right ventricular systolic pressure showed a strain-specific effect. Increased gene expression of inflammatory, muscle, and angiogenesis genes were seen in all strains, though the specific genes changed varied among groups. These results suggest that different strains use different gene expression mechanisms to adapt to the challenge of chronic hypoxia, resulting in modified phenotypic changes.


Cancer Gene Therapy | 2012

Upregulated p53 expression activates apoptotic pathways in wild-type p53-bearing mesothelioma and enhances cytotoxicity of cisplatin and pemetrexed.

Quanhai Li; Kiyoko Kawamura; Makako Yamanaka; Shinya Okamoto; Shan Yang; Suguru Yamauchi; Toshihiko Fukamachi; Hiroki Kobayashi; Yuji Tada; Yuichi Takiguchi; Koichiro Tatsumi; Hideaki Shimada; Kenzo Hiroshima; Masatoshi Tagawa

The majority of malignant mesothelioma possesses the wild-type p53 gene with a homologous deletion of the INK4A/ARF locus containing the p14ARF and the p16INK4A genes. We examined whether forced expression of p53 inhibited growth of mesothelioma cells and produced anti-tumor effects by a combination of cisplatin (CDDP) or pemetrexed (PEM), the first-line drugs for mesothelioma treatments. Transduction of mesothelioma cells with adenoviruses bearing the p53 gene (Ad-p53) induced phosphorylation of p53, upregulated Mdm2 and p21 expression levels and decreased phosphorylation of pRb. The transduction generated cleavage of caspase-8 and -3, but not caspase-9. Cell cycle analysis showed increased G0/G1- or G2/M-phase populations and subsequently sub-G1 fractions, depending on cell types and Ad-p53 doses. Transduction with Ad-p53 suppressed viability of mesothelioma cells and augmented the growth inhibition by CDDP or PEM mostly in a synergistic manner. Intrapleural injection of Ad-p53 and systemic administration of CDDP produced anti-tumor effects in an orthotopic animal model. These data collectively suggest that Ad-p53 is a possible agent for mesothelioma in combination with the first-line chemotherapeutics.


Cancer Gene Therapy | 2013

Gene therapy for malignant mesothelioma: Current prospects and challenges

Masatoshi Tagawa; Yuji Tada; Hideaki Shimada; Kenzo Hiroshima

Malignant mesothelioma, developed in the thoracic cavity, is resistant to current treatments. Suppression of the local tumor growth is beneficial to the patients since mesothelioma infrequently metastasizes to extrapleural organs. A majority of the tumors have a homologous genetic deletion at the INK4A/ARF locus that includes the p14ARF and the p16INK4A genes, and the genetic defect results in an inactivation of the p53-mediated pathways and in progression of cell cycle through pRb phosphorylation. Preclinical studies targeting the genetic abnormality with adenoviruses showed that restoration of the p53 pathways induced pRb dephosphorylation and subsequently produced anti-tumor effects. A number of preclinical studies with different genes and vector systems demonstrated the therapeutic efficacy and raised the possibility of gene therapy in clinical settings. An intrapleural administration of vectors has several advantages in transducing pleural mesothelioma but activates rapid antibody production which impedes further gene expression. There have been several clinical studies conducted for mesothelioma and these trials showed the feasibility of intrapleural administrations of adenovirus vectors. In this review we summarize major preclinical and clinical gene therapy for mesothelioma, and discuss the advantages of gene therapy in the context of stimulating host immune systems. Accumulating clinical data suggest that an intrapleural administration of viral vectors has distinct aspects which are not observed in other administration routes.


Cancer Gene Therapy | 2014

Combination of adenoviruses expressing melanoma differentiation-associated gene-7 and chemotherapeutic agents produces enhanced cytotoxicity on esophageal carcinoma

Guangyu Ma; Kiyoko Kawamura; Y Shan; Shinya Okamoto; Quanhai Li; M Namba; Masato Shingyoji; Yuji Tada; Koichiro Tatsumi; Kenzo Hiroshima; Hideaki Shimada; Masatoshi Tagawa

We examined the combinatory antitumor effects of adenoviruses expressing human mda-7/IL-24 gene (Ad-mda-7) and chemotherapeutic agents on nine kinds of human esophageal carcinoma cells. All the carcinoma cells expressed the melanoma differentiation-associated gene-7/interleukin-24 (MDA-7/IL-24) receptor complexes, IL-20R2 and either IL-20R1 or IL-22R1, and were susceptible to Ad-mda-7, whereas fibroblasts were positive only for IL-20R2 gene and resistant to Ad-mda-7-mediated cytotoxicity. Sensitivity of these esophageal carcinoma cells to Ad-mda-7 was however lower than that to Ad expressing the wild-type p53 gene. We thereby investigated a possible combination of Ad-mda-7 and anticancer agents and found that Ad-mda-7 with 5-fluorouracil (5-FU), cisplatin, mitomycin C or etoposide produced greater cytotoxic effects than those by Ad-mda-7 or the agent alone. Half-maximal inhibitory concentration values of the agents in respective cells were decreased by the combination with Ad-mda-7. Cell cycle analyses showed that Ad-mda-7 and 5-FU increased G2/M-phase and S-phase populations, respectively, and the combination augmented sub-G1 populations. Ad-mda-7-treated cells showed cleavages of caspase-8, -9 and -3 and poly (ADP-ribose) polymerase, but the cleavage levels were not different from those of the combination-treated cells. Ad-mda-7 treatments upregulated Akt phosphorylation but suppressed IκB-α levels, whereas 5-FU treatments induced phosphorylation of p53 and extracellular signal-regulated protein kinases 1 and 2. Molecular changes caused by the combination were similar to those by Ad-mda-7 treatments, but the Ad-mda-7-mediated upregulation of Akt phosphorylation decreased with the combination. These data collectively suggest that Ad-mda-7 induced apoptosis despite Akt activation and that the combinatory antitumor effects with 5-FU were produced partly by downregulating the Ad-mda-7-induced Akt activation.


Cancer Gene Therapy | 2015

Expression of p53 synergistically augments caspases-mediated apoptosis induced by replication-competent adenoviruses in pancreatic carcinoma cells.

Y Takei; Shinya Okamoto; Kiyoko Kawamura; Yuanyuan Jiang; Takao Morinaga; Masato Shingyoji; Ikuo Sekine; Shuji Kubo; Yuji Tada; Koichiro Tatsumi; Hideaki Shimada; Kenzo Hiroshima; Naoto Yamaguchi; Masatoshi Tagawa

We examined cytotoxicity of replication-competent type 5 adenoviruses (Ad5) in human pancreatic carcinoma cells with a p53-defective genotype. The replication-competent Ad5 of which E1A gene was activated by exogenous transcriptional regulatory sequences, derived from the midkine and survivin genes, achieved cytotoxicity to the pancreatic carcinoma. These cells were susceptible to replication-incompetent Ad5 expressing the wild-type p53 gene. We also produced the replication-competent Ad5 bearing the same exogenous regulatory sequences and the type 35 Ad-derived fiber-knob region, and showed that the cytotoxicity was comparable to that of the replication-competent Ad5 prototype. We then investigated possible combinatory effects of the fiber-modified replication-competent Ad and Ad5 expressing the wild-type p53 gene, both of which did not interfere respective infections. The combination produced synergistic cytotoxic effects with enhanced cleavages of caspase-3 and PARP molecules, and with increased sub-G1 fractions and annexin V-positive populations although the viral production of the replication-competent Ad was rather suppressed by expressed p53. Pancreatic cells infected with both Ad showed increase of p53 and decrease of MDM2 and p21 levels, compared with those infected with Ad expressing the p53 gene. These data collectively indicated that replication-competent Ad augmented susceptibility of pancreatic cells to apoptosis through upregulated p53 expression.


Journal of Gene Medicine | 2004

Adenoviral gene transfer to the neonatal rat pulmonary circulation

James West; Mark Buchholz; Allan Fiero; Yuji Tada; Karen A. Fagan; David M. Rodman

Gene delivery to the pulmonary circulation has been studied in adult animals, but has not been extensively investigated in neonates.


Archive | 2016

Additional file 1: Figure S1. of Combination of a third generation bisphosphonate and replication-competent adenoviruses augments the cytotoxicity on mesothelioma

Yuanyuan Jiang; Boya Zhong; Kiyoko Kawamura; Takao Morinaga; Masato Shingyoji; Ikuo Sekine; Yuji Tada; Koichiro Tatsumi; Hideaki Shimada; Kenzo Hiroshima; Masatoshi Tagawa

Genetic deletion or loss of expression of the p14 and p16 genes in mesothelioma. (A) Polymerase chain reactions to detect the INK4A/ARF region, encoding the p14 and p16 genes. The p14 gene is comprised by exon 1β, 2 and 3, and the p16 is exon 1α, 2 and 3. NCI-H28, EHMES-10 and NCI-H2452 cells were defective of the p14 and p16 genes. (B) Reverse transcription-polymerase chain reactions to detect the p14 and the p16 transcripts with primers that amplified between exon 1β and 2 (for the p14) and exon 1α and 2 (for the p16). Met-5A cells and GAPDH (glyceraldehyde-3-phosphate dehydrogenase) were used for a positive and a loading control, respectively. MSTO-211H and NCI-H226 cells were negative for the p14 and the p16 transcripts. (PPTX 46 kb)


Chest | 2005

Interleukin-6 Causes Mild Pulmonary Hypertension and Augments Hypoxia-Induced Pulmonary Hypertension in Mice

Scott M. Golembeski; James West; Yuji Tada; Karen A. Fagan


Chest | 2005

Suppression of Type II Bone Morphogenic Protein Receptor in Vascular Smooth Muscle Induces Pulmonary Arterial Hypertension in Transgenic Mice

James West; Yuji Tada; Karen A. Fagan; Wolfgang Steudel; Brian Fouty; Julie Harral; Marloes Miller; John Ozimek; Rubin M. Tuder; David M. Rodman


Archive | 2016

bone morphogenetic protein receptor gene II in transgenic mice expressing a dominant-negative type Rho-kinase inhibition alleviates pulmonary hypertension

Tadashi Yasuda; Yuji Tada; Nobuhiro Tanabe; Koichiro Tatsumi; James West

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James West

Anschutz Medical Campus

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