PubMed Health⌕ Search

Biomedical subjects

Shogo Yamada

Publications and source records attributed to Shogo Yamada.

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

MDM2: a novel mineralocorticoid-responsive gene involved in aldosterone-induced human vascular structural remodeling.

Aldosterone has been demonstrated to play an important role in the pathogenesis of various cardiovascular diseases. Vascular structural remodeling, including vascular smooth muscle cell (VSMC) proliferation, has been also reported in small resistance arteries of patients with primary aldosteronism. Therefore, in this study, we examined whether genes involved in the regulation of the cell cycle were induced by aldosterone alone in cultured human VSMCs and in human small resistance arteries. Results of these studies eventually demonstrated that MDM2, one of the genes involved in anti-apoptosis and cell growth, was markedly increased in mineralocorticoid receptor (MR)-positive VSMCs by aldosterone in all microarray, reverse transcriptase-polymerase chain reaction, immunoblotting, and immunofluorescence analyses. In addition, an analysis using small interfering RNA demonstrated that this gene product was involved in cell proliferation of VSMCs induced by aldosterone. Eplerenone, a specific MR antagonist, inhibited this gene induction by aldosterone in VSMCs. MDM2 protein was also more abundant in VSMCs of small resistance arteries in patients with primary aldosteronism compared with a control population. MDM2 is therefore considered one of the mineralocorticoid-responsive genes that regulates cell proliferation of VSMCs induced by MR-mediated aldosterone stimulation, possibly playing an important role in aldosterone-induced vascular structural remodeling.

Aldosterone↗
PubMed2006

Expression of thymidine phosphorylase and VEGF in esophageal squamous cell carcinoma.

The purpose of this study was to determine the role of TP and VEGF in angiogenesis and its clinical significance in prognosis of patients with esophageal carcinoma. Expressions of TP and VEGF, microvascular density and cell proliferation activity were evaluated by using 40 immunohistochemically stained resected esophageal carcinoma tissues, and the survival rate of the patients was analyzed. Significant positive correlation and regression were found between the VEGF expression level of tumor and microvascular density (r=0.73, p<0.0001). Not statistically strong but significant positive correlation and regression were found between the TP expression level of tumor and microvascular density (r=0.32, p=0.046). No significant relationships were found between TP and VEGF expressions. Pathological T-factor and pathological N-factor were significant prognostic factors. Tumor length, site of lesion, gender, age, and Ki67 labeling index were not significant prognostic factors. The VEGF expression level was one of the unfavorable prognostic factors (risk ratio =1.035, 95% CI=1.007-1.065, p=0.01). The patients with high TP expression showed a tendency for unfavorable prognosis, but it was not statistically significant (RR=1.017, 95% CI=0.996-1.042, p=0.1). The prognosis of patients in the TP/VEGF[+/+] group was significantly poorer than that of the patients in the TP/VEGF[-/-] group and TP/VEGF[+/- or -/+] group (RR=0.488 for TP/VEGF[-/-] group, =0.717 for TP/VEGF[+/- or -/+] group, p=0.005). In conclusion, VEGF and TP expression seems to have a relationship with tumor angiogenesis, and co-expression of TP and VEGF seemed to be one of the unfavorable prognostic factors.

Aged↗
PubMed2006

S-1, an oral fluoropyrimidine, enhances radiation response of DLD-1/FU human colon cancer xenografts resistant to 5-FU.

S-1, a novel oral fluoropyrimidine, is increasingly used for the treatment of human cancer including gastrointestinal carcinomas. Using the 5-FU resistant DLD-1/FU human colon cancer cell xenografts, the present study investigated whether S-1 enhances the therapeutic efficacy of radiation and if so what are the underlying mechanisms. Nude mice bearing tumor xenografts were treated with radiation, S-1, or both. Tumor growth delay was the treatments' endpoint. To determine whether S-1 enhances intrinsic cell radiosensitivity, we performed clonogenic cell survival assay. Also we assessed the expression of thymidylate synthase (TS) using immunohistochemistry assay. While S-1 or 5 Gy were only slightly effective as single agents in delaying tumor growth, the combined treatment was highly effective. Clonogenic cell survival showed that S-1 strongly enhanced cell radiosensitivity. Immunohistochemistry showed that the expression of TS was down-regulated in tumors treated by S-1 plus radiation. Combined S-1 plus radiation treatment resulted in a synergistic effect in the therapy of 5-FU resistant human colon carcinoma xenografts (EF = 2.06). The effect could be attributed to the ability of S-1 to increase cell radiosensitivity (EF = 1.9) and to the down-regulation of TS involved in cellular processes leading to radio- and (or) chemo-resistance.

Administration, Oral↗
PubMed2005

Salvage radiation therapy for residual superficial esophageal cancer after endoscopic mucosal resection.

PURPOSE: To analyze the outcomes of radiation therapy for patients with residual superficial esophageal cancer (rSEC) after endoscopic mucosal resection (EMR). METHODS AND MATERIALS: From May 1996 to October 2002, a total of 30 rSEC patients without lymph node metastasis received radiation therapy at Tohoku University Hospital and associated hospitals. The time interval from EMR to start of radiation therapy ranged from 9 to 73 days (median interval, 40 days). Radiation doses ranged from 60 Gy to 70 Gy (mean dose, 66 Gy). Chemotherapy was used in 9 of 30 patients (30%). RESULTS: The 2-year, 3-year, and 5-year overall survival rates and cause-specific survival rates were 91%, 82%, and 51%, respectively, and 95%, 85%, and 73%, respectively. The 2-year, 3-year, and 5-year local control rates for mucosal cancer were 91%, 91%, and 91%, respectively, and those for submucosal cancer were 89%, 89%, and 47%, respectively. These differences in survival rates for patients with two types of cancer were not statistically significant. Local recurrence and lymph node recurrence were more frequent in patients with submucosal cancer than in patients with mucosal cancer (p = 0.38 and p = 0.08, respectively). Esophageal stenosis that required balloon dilatation developed in 3 of the 30 patients, and radiation pneumonitis that required steroid therapy developed in 1 patient. CONCLUSIONS: Radiation therapy is useful for preventing local recurrence after incomplete EMR.

Aged↗
PubMed2005

Dosimetric correlations of acute esophagitis in lung cancer patients treated with radiotherapy.

PURPOSE: To evaluate the factors associated with acute esophagitis in lung cancer patients treated with thoracic radiotherapy. METHODS AND MATERIALS: We examined 35 patients with non-small-cell lung cancer (n = 27, 77%) and small-cell lung cancer (n = 8, 23%) treated with thoracic radiotherapy between February 2003 and November 2004. The median patient age was 70 years (range, 50-83 years). The disease stage was Stage I in 2 patients (6%), Stage II in 1 (3%), Stage IIIa in 10 (28%), Stage IIIb in 9 (26%), and Stage IV in 9 (26%); 4 patients (11%) had recurrent disease after surgery. A median dose of 60 Gy (range, 50-67 Gy) was given to the isocenter and delivered in single daily fractions of 1.8 or 2 Gy. With heterogeneity corrections, the median given dose to the isocenter was 60.3 Gy (range, 49.9-67.2 Gy). Of the 35 patients, 30 (86%) received concurrent chemotherapy consisting of a platinum agent, cisplatin or carboplatin, combined with paclitaxel in 18 patients (52%), irinotecan hydrochloride in 7 (20%), vincristine sulfate and etoposide in 2 (5%), vinorelbine ditartrate in 1 (3%), etoposide in 1 (3%), and docetaxel in 1 patient (3%). Three of these patients underwent induction therapy with cisplatin and irinotecan hydrochloride, administered before thoracic radiotherapy, and concurrent chemotherapy. Esophageal toxicity was graded according to the Radiation Therapy Oncology Group criteria. The following factors were analyzed with respect to their association with Grade 1 or worse esophagitis by univariate and multivariate analyses: age, gender, concurrent chemotherapy, chemotherapeutic agents, maximal esophageal dose, mean esophageal dose, and percentage of esophageal volume receiving >10 to >65 Gy in 5-Gy increments. RESULTS: Of the 35 patients, 25 (71%) developed acute esophagitis, with Grade 1 in 20 (57%) and Grade 2 in 5 (14%). None of the patients had Grade 3 or worse toxicity. The most significant correlation was between esophagitis and percentage of esophageal volume receiving >35 Gy on univariate (p = 0.002) and multivariate (p = 0.018) analyses. CONCLUSION: The percentage of esophageal volume receiving >35 Gy was the most statistically significant factor associated with mild acute esophagitis.

Acute Disease↗
PubMed2005

Construction of a remote radiotherapy planning system.

BACKGROUND: We constructed a remote radiotherapy planning system, and we examined the usefulness of and faults in our system in this study. METHODS: Two identical radiotherapy planning systems, one installed at our institution and the other installed at an affiliated hospital, were used for radiotherapy planning. The two systems were connected by a wide area network (WAN), using a leased line. Beam data for the linear accelerator at the affiliated hospital were installed in the two systems. During the period from December 2001 to December 2002, 43 remote radiotherapy plans were made using this system. RESULTS: Data were transmitted using a file transfer protocol (FTP) software program. The 43 radiotherapy plans examined in this study consisted of 13 ordinary radiotherapy plans, 28 radiotherapy plans sent to provide assistance for medical residents, and 2 radiotherapy plans for emergency cases. There were ten minor planning changes made in radiotherapy plans sent to provide assistance for medical residents. CONCLUSION: Our remote radiotherapy planning system based on WAN using a leased line is useful for remote radiotherapy, with advantages for both radiation oncologists and medical residents.

Hospital Information Systems↗
PubMed2005

3beta-Hydroxysteroid dehydrogenase in human aorta.

3beta-Hydroxysteroid dehydrogenase (3beta-HSD) is known to be involved in steroid production and/or metabolism and to be expressed in many tissues including adrenal cortex. Expression of this enzyme has also been elucidated in human cardiovascular system but its details remain largely unknown. Therefore, in this study, we examined the status of 3beta-HSD in postmortem human aorta utilizing RT-PCR and immunohistochemical analysis. Both mRNAs and immunoreactivity for the enzyme were detected predominantly in female aorta, and in those with mild atherosclerotic changes. In addition, immunohistochemical study demonstrated that immunoreactivity for 3beta-HSD was detected in vascular smooth muscle cells (VSMCs) of aorta. These findings all indicated that steroidogenesis via 3beta-HSD may occur in VSMCs of human aorta, possibly related to gender differences and/or the degree of atherosclerosis.

3-Hydroxysteroid Dehydrogenases↗
PubMed2005

Progesterone receptor subtypes in vascular smooth muscle cells of human aorta.

Progesterone is involved in various functions of the cardiovascular system, including those of vascular smooth muscle cells (VSMCs) via progesterone receptor (PR). Progesterone has also been postulated to be involved in inhibition of VSMC proliferation via PR. However, the details of PR expression have remained largely unknown in human cardiovascular VSMCs. Therefore, we first examined the relative levels of PR isoform (PR-A and PR-B) expression in VSMCs, using both immunohistochemistry and quantitative RT-PCR analysis. PR-B was equally expressed between male and female aorta, but PR-A was more abundant in female than in male aorta. This finding demonstrated that the status of PR subtype expression was associated with the difference of genders.

Adult↗
PubMed2005

In situ androgen producing enzymes in human prostate cancer.

Androgens have been proposed to be actively produced in situ in human prostate cancer. These locally produced androgens have also been considered to play important roles in the pathogenesis and development of prostate cancer. Therefore, it is important to examine the status of this in situ androgen metabolism and/or synthesis in detail in order to improve the clinical response to hormonal therapy in patients diagnosed with prostate cancer. Several studies have previously demonstrated the expression of androgen-producing enzymes such as 5alpha-reductase types 1 and 2, and 17beta-hydroxysteroid dehydrogenase type 5 (17beta-HSD5), in human prostate carcinoma cells. However, their biological significance has remained largely unknown. In this study, we evaluated the immunoreactivities of these steroidogenic enzymes in human prostate cancer obtained from surgery (n = 70), and correlated the findings with clinicopathological features of the patients. 17Beta-HSD5 immunoreactivity was detected in 54 cases (77%), 5alpha-reductase type 1 in 51 cases (73%) and 5alpha-reductase type 2 in 39 cases (56%). 5Alpha-reductase type 2 immunoreactivity was significantly correlated with that of androgen receptor (AR), and 17beta-HSD5 positive cases were significantly associated with clinical stage (TNM stage pT3 vs pT2). These data all suggest that androgen-producing enzymes, such as 5alpha-reductase type 1 and type 2, and 17beta-HSD5 are expressed in a majority of prostate cancers, and are involved in the local production and actions of androgens in prostate cancers.

17-Hydroxysteroid Dehydrogenases↗
PubMed2005

Evaluation of inter- and intrafraction organ motion during intensity modulated radiation therapy (IMRT) for localized prostate cancer measured by a newly developed on-board image-guided system.

PURPOSE: To investigate prostatic organ motion at both setup and intrafraction using an onboard image-guided system. An intrafraction field-based repositioning method also was evaluated. MATERIALS AND METHODS: A dual fluoroscopy with amorphous-silicon flat panel (DFFP) system was used for the three-dimensional registration of implanted markers in the prostate of eight organ-confined cancer patients planned for treatment with intensity modulated radiation therapy (IMRT). Day-to-day motion errors were quantified and intrafraction displacements of more than +/-1 mm were corrected. RESULTS: Among 214 fractions and 565 system views, day-to-day mean magnitude of marker discrepancy +/- standard deviation (SD) was 1.76 +/- 1.4 mm, 3.14 +/- 1.6 mm, and 3.78 +/- 2.4 mm in the right-left, cranial-caudal, and anterior-posterior directions, respectively. The intrafractional mean magnitude +/- SD of marker displacement was 0.45 +/- 0.7 mm, 1.08 +/- 1.38 mm and 1.45 +/- 1.70 mm in the right-left, cranial-caudal, and anterior-posterior directions, respectively. Intrafraction corrected sessions (84/214) showed a median (range) of motion of 0.1 mm (-1.2 to 0.7 mm), -0.2 mm (-2.1 to 1.1 mm), and -0.2 mm (-1.7 to 2.0 mm) in the right-left, cranial-caudal, and anterior-posterior directions, respectively. CONCLUSION: Motion uncertainty can be considerably decreased with daily use of the DFFP system. Reduced intrafraction organ motion clearly endorsed the value of the repositioning approach, allowing a safer dose escalation protocol.

Fluoroscopy↗
PubMed2005

[Development of [18F]FRP-170 injection for imaging hypoxia by PET].

A novel [18F]FRP-170 injection for imaging hypoxia by PET was developed for clinical use. The preparation was based on the simple on-column basic-hydrolysis and the whole procedure was automated by detecting He flow change for transferring and evaporating liquids. [18F]FRP-170 was prepared in around 15-20% decay-corrected radiochemical yield within 60 min and stable in saline for more than 6 hr. Radiochemical purity was over 99% and specific activity at EOS was 40-60 GBq/micromol. The radiation-absorbed dose to the whole body was estimated to be 1.0 mSv/185 MBq. The [18F]FRP-170 injection proved to be suitable for clinical use without acute toxicity or mutagenicity.

Animals↗
PubMed2005

[A case of high FDG-uptake into the myocardium after radiotherapy for esophageal cancer].

Radiation-induced cardiac disease has been observed in patients who have been irradiated to the mediastinum. A 68-year-old man who had been treated with chemoradiotherapy for esophageal cancer showed high FDG-uptake in his myocardium six months after the radiotherapy. The area of high FDG-uptake closely matched the irradiation field. This area also showed low 123I-BMIPP-uptake and delayed enhancement on Gd-MRI. These findings suggested the likelihood of radiation cardiomyopathy. There have been several studies on the detection of radiation cardiomyopathy by perfusion imaging, but few on detection by metabolic imaging or MRI. Early visualization and quantification of the degree of radiation cardiomyopathy might be possible by FDG-PET and 123I-BMIPP Gd-MRI.

Aged↗
PubMed2005

Long-term outcome of breast-conserving therapy for breast cancer.

PURPOSE: We present a retrospective analysis of long-term therapeutic results for patients treated in our institution to evaluate the efficacy of breast-conserving therapy (BCT). PATIENTS AND METHODS: The study population was 99 patients (102 breasts) with stage 0, I, and II breast cancer who underwent breast conservation therapy between April 1990 and November 1997. The entire breast was irradiated to a median dose of 50 Gy (range, 50-60 Gy) in 25-30 fractions. An additional 10 Gy in five fractions with 6-12 MeV electrons was given to 23 breasts (23%) with positive surgical margins. RESULTS: The 5-/10-year overall survival, cause-specific survival, relapse-free rate, local recurrence, and regional recurrence rates were 94.6/93.3%, 95.7/94.5%, 88.2/77.5%, 4.2/8.5%, and 2.0/6.3%, respectively. In both uni- and multivariate analyses, age < 40 years was a significant prognostic factor for local recurrence. No severe morbidity was observed. CONCLUSION: The long-term clinical outcome of BCT for early breast carcinoma patients in our department was favorable. Patient age <40 was the most important factor associated with an increased risk of local recurrence in the ipsilateral breast.

Adult↗
PubMed2004

A multi-institutional retrospective analysis of external radiotherapy for mucosal melanoma of the head and neck in Northern Japan.

PURPOSE: A multi-institutional retrospective study was performed in northern Japan to analyze the outcome of external radiotherapy as the definitive treatment modality for localized mucosal melanoma of the head and neck. PATIENTS AND METHODS: Thirty-one patients with localized mucosal melanoma of the head and neck treated by external radiotherapy at nine institutions of the Northern Japan Radiation Therapy Oncology Group between 1980 and 1999 were enrolled in this study. Radiotherapy alone was performed in 21 patients, and the remaining 10 patients received postoperative radiotherapy for gross residual tumors. The fraction size of radiotherapy varied from 1.5-13.8 Gy, with the total dose ranging from 32-64 Gy (median, 50 Gy). The follow-up periods ranged from 1-214 months (median, 16 months). RESULTS: Complete or partial responses were observed in 9 patients (29%) and 18 patients (58%), respectively. Local recurrence occurred in 13 patients (41.9%) and distant metastasis occurred in 11 patients (35.5%). Most incidences of local recurrence and distant metastasis developed within 2 years after the initial treatment. Overall cause-specific survival rates of patients at 1 and 3 years were 73% and 33%, respectively. Univariate analysis showed that high dose per fractionated radiotherapy doses (>or=3 Gy) was associated with better prognosis for both local control (p = 0.048) and survival (p = 0.045). Multivariate analysis indicated that age (better prognosis in younger patients, p = 0.046) was the only significant factor. Radiotherapy for gross residual lesions after surgery did not seem to impact the significant gain of local control and survival. We observed two fatal late complications of mucosal ulcer and bleeding in the high dose per fractionated radiotherapy group. CONCLUSION: Radiotherapy at a dose of 3 Gy or more per fraction was effective in gaining local control in patients with localized mucosal melanoma of the head and neck, and subsequently better survival was possible, especially in younger patients.

Adult↗
PubMed2004

Estrogen receptors in atherosclerotic human aorta: inhibition of human vascular smooth muscle cell proliferation by estrogens.

Estrogen has been postulated to exert direct anti-atherogenic effects via binding to estrogen receptors (ERs) in vascular smooth muscle cells (VSMCs). Therefore, we believe it is important to examine the status of ER expression in the human cardiovascular system and its disorders. In this study, we first evaluated the relative abundance of messenger RNA (mRNA) of both ER subtypes (ERalpha and ERbeta) in the human aorta using reverse transcription followed by quantitative polymerase chain reaction (RT-qPCR). We then examined the immunolocalization of both ERs in VSMCs of human atherosclerotic lesions. In order to examine which ER subtype was associated with the anti-atherogenic effects of estrogen, we examined the effects of estrogen in two VSMC cell lines, one positive only for ERalpha and the other positive only for ERbeta. The relative abundance of mRNAs for both ERs was higher in female aorta with a mild degree of atherosclerosis than in female aorta with a severe degree of atherosclerosis (P < 0.05). In addition, the number of ERalpha and/or ERbeta double positive cells in the neointima was higher in female aorta with a mild degree of atherosclerosis than in female aorta with severe atherosclerosis (P < 0.05). Our in vitro study found that estradiol was able to significantly inhibit the proliferation of ERalpha positive VSMCs but not ERbeta positive VSMCs (P < 0.05). Moreover, estradiol was found to significantly suppress proliferating cell nuclear antigen (PCNA) mRNA levels in ERalpha positive VSMCs compared to that of ERbeta positive VSMCs, consistent with the findings of cell proliferation. Results from this study suggest that estrogens can inhibit the proliferation of VSMCs through ERalpha, especially in pre-menopausal women. Our study also indicates that decreased levels of ER, especially ERalpha, in the female atherosclerotic neointima may be associated with progression of atherosclerotic changes.

Actins↗
PubMed2004

Univariate analysis of factors correlated with tumor control probability of three-dimensional conformal hypofractionated high-dose radiotherapy for small pulmonary or hepatic tumors.

PURPOSE: To show the factors correlated with tumor control probability (TCP) after three-dimensional conformal hypofractionated high-dose radiotherapy (3D-CHHRT) for small pulmonary or hepatic tumors. METHODS AND MATERIALS: We enrolled 34 patients with 42 lesions (13 lung carcinomas, 6 hepatocellular carcinomas, and 23 lung or liver metastases) treated with 3D-CHHRT alone, with simple immobilization devices, between July 1997 and January 2002. We prescribed 45 Gy in three fractions at the 90-100% isodose line of the planning target volume. The median follow-up period was 18 months (range, 4-46 months). We calculated the TCP using the Kaplan-Meier method and univariate analysis for the following factors: age, gender, primary site, histologic type, tumor size, and previous treatment. RESULTS: Overall, the 2-year TCP of 3D-CHHRT was 83.6%. Local recurrence was observed in 6 lesions within 1 year after treatment. We showed that tumor size was the only significant factor to correlate with the TCP in univariate analysis. The 2-year TCP for tumors <3 cm or > or =3 cm in diameter was 95.0% and 58.3%, respectively (p = 0.0022). No severe adverse effects were observed. CONCLUSION: The TCP for tumors <3 cm in diameter was excellent for 3D-CHHRT.

Adenocarcinoma↗
PubMed2004

Relationships between radiosensitivity and microvascular density in esophageal carcinoma: significance of hypoxic fraction.

PURPOSE: The prognosis and the radiosensitivity of macroscopically infiltrative type of esophageal carcinoma are worse than those of the localized type of esophageal carcinoma treated with irradiation. The aim of this study was to investigate the cause of differences in radiosensitivity and prognosis of esophageal carcinoma according to macroscopic type from the viewpoint of tumor angiogenesis. METHODS AND MATERIALS: A total of 40 surgically resected esophageal carcinoma tissues with good material remaining were selected at random from macroscopically localized type (n = 20) and infiltrative type (n = 20) of esophageal carcinoma. The highest intratumoral microvascular density (h-MVD), average intratumoral microvascular density (a-MVD), Ki67 labeling index, and expression of vascular endothelial growth factor (VEGF) in each section were estimated. RESULTS: h-MVD was significantly (p = 0.0006) greater in the infiltrative type than in the localized type, whereas a-MVD (p = 0.0014) and Ki67 labeling index (p = 0.022) were significantly lower in the infiltrative type than in the localized type. The expression level of VEGF was significantly (p < 0.0001) higher in the infiltrative type. CONCLUSIONS: The generally underdeveloped vascular densities with low proliferation activities (suggesting increase of hypoxic fraction) seemed to be one of the reasons for unfavorable radiosensitivities of infiltrative type of esophageal carcinoma. The infiltrative type of esophageal carcinoma shows a high level of VEGF expression and high activity of tumor angiogenesis. The locally enhanced neovascularization, which occurs frequently in hematogenous metastasis seemed to be one of the reasons for the unfavorable prognosis of the infiltrative type of esophageal carcinoma.

Aged↗