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Hiroshi Wada

Publications and source records attributed to Hiroshi Wada.

At least 37 records · Page 2Linked to original sources
PubMed2006

[Intra arterial infusion chemotherapy combined with interferon-alpha following palliative hepatic resection against advanced hepatoma with portal venous tumor thrombus in the major trunk and multiple nodules--a preliminary study].

Recently, we reported the beneficial effects of intra arterial 5-FU infusion chemotherapy combined with interferon-alpha (IFN-alpha/5-FU combined chemotherapy) for advanced hepatocellular carcinoma (HCC). This report describes the preliminary results of treatment of IFN-alpha/5-FU combined chemotherapy following palliative hepatic resection for advanced hepatocellular carcinoma with tumor thrombus in the main trunk of the portal vein with multiple nodules in the whole liver. The 15 patients of HCC with portal venous tumour thrombi (PVTT) and multiple intra-hepatic multiple nodules (IM3) were treated with IFN-alpha/5-FU combined chemotherapy following palliative surgery in this study. No leukopenia, thrombocytopenia, or myelosuppression was observed in any of the 15 patients. Other adverse effects were, in general, clinically manageable. Concerning the anti-tumor effect, 6 showed an objective response and 9 showed a progressive disease; the response rate was 40.0% (6/15). The 1-year and 3-year survival rates were 48% and 21% in all 15 cases, respectively. In conclusion, IFN-alpha/5-FU combined therapy may be a promising modality for advanced HCC with tumor thrombi in the major trunk with multiple nodules after following palliative surgery.

Antimetabolites, Antineoplastic↗
PubMed2006

[A successful case of hepatocellular carcinoma with portal venous tumor thrombus (Vp2) treated by transcatheter arterial chemoembolization].

We reported a case of hepatocellular carcinoma (HCC) with portal venous tumor thrombus (PVTT) (Vp2) successfully treated by transcatheter arterial chemoembolization (TACE), and the tumor showed complete response and the patient survived for 28 months. A 67-year-old male was diagnosed with HCC in the area of subsegment 5 with PVTT from the P5 to the posterior branch. He was treated by segmental TACE. The tumor markers decreased within normal limits, and localized hepatic infraction in the subsegment 5 and atrophy of the PVTT were recognized. He survived for 28 months with no tumor recurrence after the first TACE. This case suggested that embolization might play a part of treatment to HCC with PVTT, if the liver function was preserved and the lesion of liver infraction was limited.

Aged↗
PubMed2006

[Surgical treatment for peritoneal dissemination of hepatocellular carcinoma after percutaneous ethanol injection therapy--a case report].

We report a 73-year-old man who underwent surgery for peritoneal dissemination of hepatocellular carcinoma (HCC) after percutaneous ethanol injection therapy (PEIT). He received posterior segmentectomy for HCC in 1997. Four years after the first hepatic resection, a recurrence lesion in the right caudal lobe of the liver was detected by computed tomography (CT). He underwent percutaneous ethanol injection therapy (PEIT) and transcatheter arterial embolization (TAE). He was referred to our hospital for further treatment. Abdominal CT revealed an early-enhanced lesion (3.2 cm in size) in the right caudal lobe of the liver and an irregular mass lesion (1.5 cm in size) in the cranial. We diagnosed the disease as recurrent HCC and carried out partial hepatectomy, removal of peritoneal dissemination and a reconstruction of the inferior vena cava. A histological feature of the tumor was a moderately differentiated HCC, and there was no lymphatic structure in the tumor, and no connection to the residual liver. Therefore, we diagnosed the tumor as peritoneal dissemination of HCC. We think that this is a rare but a serious complication of PEIT and every effort should be attempted to prevent this complication, especially in the treatment of superficial and larger HCC.

Aged↗
PubMed2005

Ets identified as a trans-regulatory factor of amphioxus Hox2 by transgenic analysis using ascidian embryos.

Although the functions of Hox genes in anterior-posterior patterning and their clustered organization are well conserved among metazoans, some Hox genes have lost their original function, as exemplified by zen, ftz and bicoid in Drosophila. The Hox2 gene of amphioxus has also lost its original function and instead is expressed specifically in the preoral pit. As new cis-elements governing its expression in the preoral pit must have been essential for retention of AmphiHox2, we analyzed the transcriptional regulation of AmphiHox2. Although it is possible to make transgenic amphioxus, several technical limitations restrict their practical use; thus, we analyzed the cis-regulatory region surrounding AmphiHox2 in transgenic ascidians (Ciona intestinalis). We found that Ets binding sites of AmphiHox2 functioned in the ascidian embryo. As the amphioxus Ets1/2 homologue is expressed in the preoral pit, we concluded that AmphiHox2 is activated by Ets1/2 in the preoral pit. These analyses demonstrate the utility of Ciona embryos as a transgenic system for analyses of cis-elements from animals whose embryos are relatively inaccessible, such as amphioxus and hemichordates.

Animals↗
PubMed2005

Clinical outcome of esophageal cancer patients with history of gastrectomy.

BACKGROUND: Surgery for thoracic esophageal cancer after gastrectomy involves a complicated reconstruction procedure. A surgeon's hesitation is further increased because the clinical outcome of surgical treatment of these patients has not been elucidated. OBJECTIVES: Among 948 thoracic esophageal cancer patients who underwent curative operation, 72 (7.6%) had a history of gastrectomy. Their clinico-pathological features and survival (follow-up average 881 days) were compared with those without gastrectomy. RESULTS: Esophagectomy for patients after gastrectomy was performed via right thoracotomy (66), left thoracotomy (4), and transhiatal resection (2), and reconstruction was done using the right-side colon (57) or jejunum (15). Compared to non-gastrectomized patients, gastrectomized patients were exposed to longer operation time (523 min vs. 460 min), but no significant difference was observed in operative mortality (4.2% vs. 2.5%) or blood loss (1,189 ml vs. 990 ml). Pathological examination showed no significant difference in depth of tumor invasion, lymph node metastasis, and TNM staging between gastrectomized and non-gastrectomized patients, while tumors were located at lower position in the gastrectomized patients (P = 0.046). The overall and cause-specific 5-year survival rates were 56% and 65% for gastrectomized esophageal cancer patients, which were significantly better than for non-gastrectomized patients (36% and 44%, P = 0.0235 and 0.024, respectively). Multivariate analysis showed gastrectomy as a marginally independent factor for a favorable prognosis (hazard ratio 1.832, P = 0.0324). With respect to tumor recurrence, hematogenic metastasis tended to be less frequent in gastrectomized patients than in non-gastrectomized patients. In gastrectomized patients, neither disease (peptic ulcer or gastric cancer) nor reconstruction (Billroth-I, Billroth-II, and Roux-Y) for gastrectomy affected the clinicopathological findings or post-operable survival. CONCLUSIONS: Surgical treatment of esophageal cancer patients after gastrectomy was complicated but tolerable, and should be considered as a reliable therapeutic modality because of favorable patient prognosis.

Adult↗
PubMed2005

Combination of IFN-alpha and 5-fluorouracil induces apoptosis through IFN-alpha/beta receptor in human hepatocellular carcinoma cells.

PURPOSE: Several studies showed the effectiveness of combination therapy with IFN-alpha and 5-fluorouracil (5-FU) for advanced hepatocellular carcinoma. However, only little is known about the underlying mechanism of combination therapy. In the present study, we examined whether apoptosis through IFN-alpha/beta receptor (IFN-alpha/betaR) was associated with the effects of combination therapy. EXPERIMENTAL DESIGN: HuH7, PLC/PRF/5, HLE, and HLF were treated with IFN- (500 units/mL), 5-FU (0.5 microg/mL), or their combination for 10 days. In addition, IFN-alpha/betaR gene transfer with combination therapy was done. RESULTS: Ten-day treatment by combination therapy resulted in >80% cell growth inhibition. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis showed synergistic effects for combination therapy on PLC/PRF/5, HLE, and HLF. Concordant results were obtained with DNA fragmentation. Moreover, there was an evidence showing that changes in the expression of Bcl-2 family lead to apoptosis. On the other hand, the expression of IFN-alpha/betaR and up-regulation of alpha-phospho-signal transducer and activator of transcription 1, IFN regulatory factor-1 by combination therapy were observed in all cell lines. Furthermore, IFN-alpha/type 2 IFN receptor long form-transfected HuH7 cells treated with combination therapy showed strong DNA fragmentation compared with nontransfected or transfected with IFN-alpha- and 5-FU-treated HuH7. CONCLUSIONS: Our results showed that combination of IFN-alpha plus 5-FU strongly induced cell growth inhibition of human hepatocellular carcinoma cells and indicated that one of the direct mechanisms of combination therapy may in part be attributable to alterations in induction of apoptosis through IFN-alpha/betaR.

Apoptosis↗
PubMed2005

Association between recurrence of hepatocellular carcinoma and alpha-fetoprotein messenger RNA levels in peripheral blood.

PURPOSE: Intra- and extrahepatic recurrence is common, even after curative resection for hepatocellular carcinoma (HCC), suggesting preoperative or intraoperative tumor cell dissemination. Reverse transcription - polymerase chain reaction (RT-PCR) for alpha-fetoprotein (AFP) is used to detect circulating liver cancer cells. We previously developed a quantitative method that allows estimation of the AFP mRNA level by real-time PCR. In the present study, we used this method to measure the AFP mRNA level before and after resection of HCC, then correlated the findings with various clinicopathological characteristics and prognosis. METHODS: We prospectively examined peripheral blood samples from 38 patients with HCC, and bone marrow aspirate from 25 of these patients. As a control, we examined bone marrow from 20 patients with benign diseases. The follow-up period ranged from 32 to 66 months. Real-time RT-PCR was used to detect AFP mRNA levels in the samples. RESULTS: AFP was expressed in 9 (23.7%) of the 38 peripheral blood samples. The detection of AFP mRNA was significantly correlated with extrahepatic metastasis after primary surgery, and a shorter disease-free survival time (P = 0.0245 each). Bone marrow samples were defined as positive if they expressed AFP mRNA at levels higher than the maximum expressed level in the controls, because only 1 (5%) of the 20 control bone marrow samples had low AFP mRNA expression. Using this cutoff level, 12 (48%) of the 25 patients with HCC had positivity for AFP mRNA. The results of bone marrow RT-PCR did not correlate with the clinocopathological characteristics of prognosis. CONCLUSIONS: Using real-time PCR to measure the AFP mRNA level in blood, but not bone marrow, could be useful for predicting postoperative tumor recurrence.

Adult↗
PubMed2005

Construction of an expression system for the motor protein prestin in Chinese hamster ovary cells.

The electromotility of outer hair cells (OHCs) is believed to be a major factor in cochlear amplification that enables the high sensitivity of hearing in mammals. This motility is thought to be based on voltage-dependent conformational changes of a motor protein embedded in the lateral wall of the OHC. In 2000, this motor protein was identified and termed prestin. To obtain knowledge on the function of prestin, research at the molecular level is necessary. For this purpose, a method of obtaining a large amount of prestin is required. In this study, an attempt was therefore made to construct an expression system for prestin. Prestin cDNA was introduced into Escherichia coli (E. coli), insect cells and Chinese hamster ovary (CHO) cells, and the expression of prestin was examined by Western blotting. As CHO cells expressed prestin well, we generated prestin-expressing cell lines using CHO cells by limiting dilution cloning. The stable expression and the activity of prestin in generated cell lines were then confirmed. Finally, to obtain prestin from these cell lines efficiently, culture conditions of the cells were examined, and it was clarified that cells should be cultured in serum-free medium and harvested around 48 h after passage.

Animals↗
PubMed2005

The phylogenetic status of Paxillosida (Asteroidea) based on complete mitochondrial DNA sequences.

One of the most important issues in asteroid phylogeny is the phylogenetic status of Paxillosida. This group lacks an anus and suckers on the tube feet in adults and does not develop the brachiolaria stage in early development. Two controversial hypotheses have been proposed for the phylogenetic status of Paxillosida, i.e., Paxillosida is primitive or rather specialized in asteroids. In this study, we determined the complete mitochondrial DNA nucleotide sequences from two paxillosidans (Astropecten polyacanthus and Luidia quinaria) and one forcipulatidan (Asterias amurensis). The mitochondrial genomes of the three asteroids were identical with respect to gene order and transcription direction, and were identical to the previously reported mitochondrial genomes of Asterina pectinifera (Valvatida) and Pisaster ochraceus (Forcipulatida) in this respect. Therefore, the comparison of genome structures was uninformative for the purposes of asteroid phylogeny. However, molecular phylogenetic analyses based on the amino acid sequences and the nucleotide sequences from the five asteroids supported the monophyly of the clade that included the two paxillosidans and Asterina. This suggests that the paxillosidan characters are secondarily derived ones.

Animals↗
PubMed2005

Phase of neural excitation relative to basilar membrane motion in the organ of Corti: theoretical considerations.

Although the auditory transduction process is dependent on neural excitation of the auditory nerve in relation to motion of the basilar membrane (BM) in the organ of Corti (OC), specifics of this process are unclear. In this study, therefore, an attempt was made to estimate the phase of the neural excitation relative to the BM motion using a finite-element model of the OC at the basal turn of the gerbil, including the fluid-structure interaction with the lymph fluid. It was found that neural excitation occurs when the BM exhibits a maximum velocity toward the scala vestibuli at 10 Hz and shows a phase delay relative to the BM motion with increasing frequency up to 800 Hz. It then shows a phase advance until the frequency reaches 2 kHz. From 2 kHz, neural excitation again shows a phase delay with increasing frequency. From 800 Hz up to 2 kHz, the phase advances because the dominant force exerted on the hair bundle shifts from a velocity-dependent Couette flow-induced force to a displacement-dependent force induced by the pressure difference. The phase delay that occurs from 2 kHz is caused by the resonance process of the hair bundle of the IHC.

Acoustic Stimulation↗
PubMed2005

Evaluation of transmural myocardial perfusion by ultra-harmonic myocardial contrast echocardiography in reperfused acute myocardial infarction.

BACKGROUND: The transmural distribution of myocardial perfusion is important for predicting the contractile reverse of an infarcted wall in reperfused acute myocardial infarction (AMI). Evaluating transmural myocardial perfusion by myocardial contrast echocardiography (MCE) could predict the long-term recovery of left ventricular (LV) function. METHODS AND RESULTS: The study group comprised 20 consecutive patients with a first-episode anterior AMI with total occlusion of the proximal left anterior descending artery, who underwent successful percutaneous coronary intervention within 24 h of onset. MCE was performed on the 15th day after the onset, using ultraharmonic gray-scale imaging with intermittent end-systolic triggering every 4 beats or every 6 beats. Regions of interest were placed over both the endocardial and epicardial region at the mid-septal level. Regional wall motion (RWM) of the infarcted anterior wall and global LV function were assessed by 2-dimensional echocardiography and left ventriculography in both the acute and chronic phase. The transmural distribution of myocardial perfusion by MCE demonstrated a significant relation with RWM score index (r = 0.75, p = 0.0004). Recovery of RWM and LV ejection fraction (LVEF) at 6 months after reperfusion was significantly greater in the group with good perfusion of the epicardium according to MCE than in the poor perfusion group [RWM (SD/cord); -1.23+/-0.91 vs -3.51+/-0.84, p = 0.001, LVEF (%); 63.8+/-10.4 vs 47.0+/-3.4, p = 0.04]. CONCLUSIONS: Assessing the transmural distribution of myocardial perfusion by MCE can predict the long-term recovery of LV function after a reperfused AMI.

Acute Disease↗
PubMed2005

[A case of HCC with inferior caval vein tumor thrombus and multiple pulmonary metastases that remarkably responded to combination therapy of TS-1 and interferon-alpha].

A 56-year-old male was admitted to our hospital for hepatoma with portal vein thrombus and multiple intrahepatic metastases. He underwent an extended left lobectomy and a partial resection of the liver in May 2002. After two weeks from the surgery, he received intra arterial 5-FU infusion chemotherapy combined with subcutaneous interferon-alpha injection to treat the lesions in the residual liver. Four months after the surgery, hepatic vein tumor thrombus appeared in the remnant liver and it extended to the inferior caval vein. And another 4 months later, multiple pulmonary metastases were detected with computed tomography and they grew rapidly in the view of their sizes and numbers. Because the combined therapy of 5-FU/interferon-alpha was not effective to distant metastases, we started a new regimen of oral administration of TS-1 and a subcutaneous interferon-alpha injection. After 1 treatment cool, hepatic vein thrombus was markedly reduced the size and vascularity in the CT. Multiple pulmonary metastases also decreased in their sizes and numbers. No adverse effect was seen during this treatment. It was suggested that a combination therapy of TS-1 and interferon-alpha may be one of the most effective treatment modalities against advanced HCC with distant metastasis.

Administration, Oral↗
PubMed2005

[A successful surgical treatment for solitary pulmonary and adrenal metastases after hepatic resection to hepatocellular carcinoma--a case report].

We report a 65-year-old man who received a successful surgical treatment for both pulmonary and adrenal metastases after curative resection to hepatocellular carcinoma (HCC). He received a partial hepatic resection for HCC of the right hepatic lobe. Thirty-eight months after the first hepatic resection, a metastatic lesion of the right pulmonary lobe was detected by computed tomography (CT). He was orally administered of UFT (600 mg/day). After 6 months of the chemotherapy, a metastatic lesion of lung became decreased in size. However, a metastatic lesion of the right adrenal gland was detected by abdominal CT scan. Fifty six months after the first operation, we performed right adrenalectomy. A further 4 months later, we performed partial resection of the right pulmonary lobe. Eight months after the pulmonary resection, intrahepatic recurrence was detected and he received transcatheter arterial embolization (TAE) twice. Eighty one months after the first operation, he died of liver failure due to tumor progression. Surgical resection for metastases from HCC resulted in long-term survival even if there were extrahepatic metastases in two different sites.

Adrenal Gland Neoplasms↗
PubMed2005

[Successful treatment of combined intraarterial (5-fluorouracil and adriamycin and cisplatin) infusion chemotherapy for advanced hepatocellular carcinoma with multiple intrahepatic metastases and/or portal vein thrombosis--two case reports].

Hepatic arterial infusion chemotherapy has been often selected as a therapeutic option for advanced hepatocellular carcinoma with multiple intrahepatic metastases and/or portal vein thrombosis. We successfully treated and obtained CR in the 2 cases of far advanced hepatocellular carcinoma with intraarterial infusion chemotherapy (FAP). Case 1 was a 71-year-old male who had advanced hepatocellular carcinoma with intrahepatic metastasis (IM3) which was recurrent after two surgeries. He received hepatic arterial infusion chemotherapy (FAP: 5-fluorouracil 500 mg/day: continuous infusion, day 1-5, adriamycin 10 mg/day, day 1, CDDP 10 mg/day, day 1). After 10 courses, abdominal CT revealed that the viable lesions had completely disappeared (CR). This patient is still alive with no recurrence after 21 months from the beginning of this treatment. Case 2 was a 74-year-old male who had advanced hepatocellular carcinoma with portal vein thrombi (Vp4) and intrahepatic metastasis (IM3). He received FAP arterial infusion chemotherapy with the same protocol as case 1. After 8 courses of this therapy, CT revealed that these lesions had disappeared (CR). This patient is still alive with no recurrence after 9 months from the beginning of this treatment. For 15 patients with advanced hepatocellular carcinoma using a same protocol, the response rate of this therapy was 33.3% (CR & PR). These findings suggested that combined arterial infusion chemotherapy of FAP may be feasible and a promising modality for the advanced HCC with intrahepatic metastases and/or portal vein thrombosis.

Aged↗
PubMed2004

Partial contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of interferon-alpha/5-fluorouracil against Hepatocellular Carcinoma.

PURPOSE: Our purpose was to explore the contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of IFNalpha and 5-fluorouracil (5-FU) combination therapy for hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: Susceptibility of HCC cell lines to TRAIL and/or 5-FU was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effects of 5-FU, IFNalpha, or both on the expression of TRAIL receptors (R1, R2, R3, and R4) on HCC cells or TRAIL in peripheral blood mononuclear cells (PBMC) were examined by flow cytometry. IFNalpha-induced cytotoxic effects of PBMC on HCC cell lines were examined by (51)Cr release assay. TRAIL expression in peripheral blood mononuclear cells and liver tissue from patients was examined by real-time reverse transcription-PCR or immunohistochemistry. RESULTS: HLE and HepG2 were sensitive to TRAIL, but HuH7, PLC/PRF/5, and HLF were resistant. 5-FU had synergistic effect on TRAIL in HLF and additive effect in four other HCC cell lines. TRAIL receptors on HCC cells were up-regulated by 5-FU, and IFNalpha induced TRAIL on CD4(+) T cells, CD14(+) monocytes, and CD56(+) NK cells. Treatment of effector cells by IFNalpha and target HCC cells by 5-FU enhanced the cytotoxicity of CD14(+) monocytes and CD56(+) NK cells against HCC cells via a TRAIL-mediated pathway. TRAIL mRNA overexpression was noted in PBMC of HCC patients who clinically responded to IFNalpha/5-FU combination therapy, and TRAIL(+) mononuclear cells were found in cancer tissue of a responder. CONCLUSION: Our results suggest that modulation of TRAIL/TRAIL receptor-mediated cytotoxic pathway might partially contribute to the anti-HCC effect of IFNalpha and 5-FU combination therapy.

Adult↗
PubMed2004

Complete nucleotide sequence of the mitochondrial genome of Doliolum nationalis with implications for evolution of urochordates.

The evolutionary history of the diverse lifestyles adopted by urochordates has attracted intense interest because it may effect the evolutionary history of vertebrates. Here, we report the complete mitochondrial (mt) DNA sequence of the pelagic thaliacean doliolid Doliolum nationalis. The doliolid mt genome shares the unusual tRNAs of trnM(uau) and trnG(ucu) with other ascidians, such as Halocynthia and Ciona. On the other hand, the gene order of the doliolid mt genome is significantly different from that of any ascidian species or vertebrate reported to date. Phylogenetic analyses of the amino acid sequences of 12 protein-coding genes strongly support the sister-grouping of doliolids and the Phlebobranch ascidian Ciona, with the Stolidobranch ascidian alocynthia as the outgroup, thereby providing strong support for the paraphyly of ascidians, as has been suggested by 18S rDNA studies. Given the paraphyletic nature of ascidians, it seems likely that the common ancestor of ascidians and thaliaceans was sessile, as are the present-day ascidians, and that the thaliaceans subsequently evolved a pelagic lifestyle.

Animals↗
PubMed2004

Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell cycle.

The concept of the plasticity or transdifferentiation of adult stem cells has been challenged by the phenomenon of cell fusion. In this work, we examined whether neonatal cardiomyocytes fuse with various somatic cells including endothelial cells, cardiac fibroblasts, bone marrow cells, and endothelial progenitor cells spontaneously in vitro. When cardiomyocytes were cocultured with endothelial cells or cardiac fibroblasts, they fused and showed phenotypes of cardiomyocytes. Furthermore, cardiomyocytes reentered the G2-M phase in the cell cycle after fusing with proliferative noncardiomyocytes. Transplanted endothelial cells or skeletal muscle-derived cells fused with adult cardiomyocytes in vivo. In the cryoinjured heart, there were Ki67-positive cells that expressed both cardiac and endothelial lineage marker proteins. These results suggest that cardiomyocytes fuse with other cells and enter the cell cycle by maintaining their phenotypes.

Adenoviridae↗