Biomedical subjects

S Egawa

Publications and source records attributed to S Egawa.

At least 19 recordsLinked to original sources

PubMed2006

Prostate-specific antigen adjusted for total prostatic tumor volume as a predictor for outcome after radical prostatectomy.

The aim of this study was to investigate the potential prognostic value of preoperative serum prostate-specific antigen levels adjusted for total tumor volume (PSA-TTV density) for outcome following radical prostatectomy for prostate cancer by retrospective review in 268 patients. Lower PSA-TTV density was not only associated with a significantly higher risk for biological failure (bF), systemic failure and cancer death but also an independent predictor for bF (hazard ratio, 6.3). Therefore, these data suggest that there are subsets of prostate cancer with lower PSA secretion levels, and this phenotype is associated with a higher risk of failure after surgery.

Aged↗

PubMed2006

Oncolytic replication-competent adenovirus suppresses tumor angiogenesis through preserved E1A region.

An adenovirus (Adv) retaining normal E1A but lacking the 55 kDa E1B protein replicates preferentially in TP53-deficient cancer cells including pancreatic cancer cell lines, resulting in the oncolysis of the tumor. When tumor cells are exposed to hypoxia, hypoxia-inducible factor-1alpha (HIF-1alpha) is stabilized and activated to promote the transcription of several genes such as vascular endothelial growth factor (VEGF), but in the presence of E1A hypoxia-induced VEGF m-RNA synthesis is inhibited by E1A binding to p300. In this study, we demonstrated that the cancer cells infected with a mutant Adv in which the p300 binding site in E1A was partially deleted induced a higher expression level of VEGF as compared to those of Adv with normal E1A. An immunoprecipitation study for E1A confirmed that mutant E1A had a reduced binding capacity for p300. Although the expressions of HIF-1alpha m-RNA were almost the same in both cancer cells infected with the mutant Adv and those with the wild Adv, the amount of HIF-1alpha protein in cancer cells infected with the wild E1A Adv was lower than in those infected with the mutant E1A type Adv. In vivo, in contrast to the angiogenesis treated with mutant E1A, wild-E1A inhibited tumor angiogenesis significantly. These results suggested that E1A suppressed the production of VEGF and inhibited tumor angiogenesis by binding with p300, resulting in the inhibition of the HIF-1alpha-mediated transcription of genes through binding to HRE. This study demonstrates, for the first time, the effect of an oncolytic replication-competent Adv in inhibiting tumor angiogenesis.

Adenoviridae↗

PubMed2005

Proteome analysis of prostate cancer.

In this paper, we briefly review cancer proteomics in general, with particular attention to our proteome analyses of prostate cancer. Our efforts include development of new tools and novel approaches to discovering proteins potentially useful as cancer diagnostic and/or prognostic biomarkers or as therapeutic targets. To this end, we analyzed prostate cancer proteomes using two-dimensional gel electrophoresis employing agarose gels for the initial isoelectric focusing step (agarose 2-DE), with mass spectrometry used for protein identification. Agarose 2-DE offers advantages over the more widely used immobilized pH gradient 2-DE for separating high molecular mass proteins (15-500 kDa), thereby increasing its power to detect changes in the cancer's high-molecular mass proteomes.

Biomarkers, Tumor↗

PubMed2005

New strategy for acute necrotizing pancreatitis: Continuous Regional Arterial Infusion (CRAI) therapy.

Acute pancreatitis is an autodigestive disease, of which protease inhibition has been the focus of experimental and clinical research. Different from Europe and the United States, protease inhibitors are often applied in the treatment of acute pancreatitis in Japan. However, in clinical settings, the effect of protease inhibitors on acute pancreatitis is still controversial. Continuous Regional Arterial Infusion (CRAI) of protease inhibitors and antibiotics therapy were developed in Japan and it has been demonstrated that CRAI therapy has beneficial effects on severe acute necrotizing pancreatitis. In the Japanese clinical guidelines for the treatment of acute pancreatitis, published in 2003, CRAI therapy is still classified as a special therapy. However, a Randomized Controlled Trial for CRAI therapy has started and CRAI therapy is expected to become a new standard therapy for severe acute pancreatitis. CRAI therapy is aimed at preventing the progression of pancreatic inflammation and pancreatic infection. CRAI therapy can decrease the mortality rate and the frequency of pancreatic infection in severe acute pancreatitis, but it should be started as soon as possible after the onset of acute pancreatitis.

Anti-Bacterial Agents↗

PubMed2004

Impact of biochemical failure on long-term clinical outcome after radical prostatectomy for prostate cancer in Japan.

Detailed information is needed to understand the impact of biochemical failure (bF) on long-term outcome after definitive therapy for prostate cancer. In all, 223 consecutive men treated with radical retropubic prostatectomy were followed and long-term clinical outcome was investigated. Pathological examination revealed more locally advanced tumors in this study compared with the typical cohorts seen in the Western series. The Cox proportional hazards model indicates pretreatment prostate-specific antigen levels and risk group stratification to be a significant predictors for bF (P<0.05), but not for overall survival. Seminal vesicle involvement was a significant predictor of systemic progression, cancer death and overall survival (P<0.05). Positive surgical margin and bF were also found to be independent predictors of overall survival (P<0.05). In contrast to reports from Western countries, this study found a significant correlation between bF after radical prostatectomy and overall survival. This may reflect years-later detection of prostate cancer in Japan compared with Western series. Biochemical failure may ultimately be translated into decreased overall survival after sufficient follow-up.

Aged↗

PubMed2003

Changes in prostate-specific antigen and hormone levels following withdrawal of prolonged androgen ablation for prostate cancer.

We conducted a study in order to characterize changes after withdrawal of androgen ablation (AA) for prostate cancer. AA was withdrawn in 38 Japanese patients with prostate cancer who had undergone this therapy for various periods. Patients were stratified into those who had undergone AA for less than 24 months (Group 1, n=12) and those with longer periods of AA (Group 2, n=26). Serial changes in hormones and prostate-specific antigen (PSA) were prospectively monitored following cessation of AA. The median durations of AA in the two groups were 8.5 and 54.5 months, respectively. Levels of total testosterone (T), luteinizing hormone and PSA increased significantly with time. At the end of 2 y, 30/38 patients (78.9%) had T levels above 50 ng/dl and 19/38 (50%) had levels above 320 ng/dl. Patients in Group 2 required significantly longer duration for T recovery. Complete T recovery is not always accompanied by rising PSA. Recovery of T levels is often slow following cessation of prolonged AA. Expression of PSA after AA is often variable and unpredictable. Thus, interpretation of outcomes in clinical trials incorporating AA needs caution and careful consideration.

Aged↗

PubMed2002

Probability of prostate cancer at various levels of per cent free prostate specific antigen in Japanese men with total PSA of 4.1-10.0 ng/ml.

Estimates for the likelihood of prostate cancer at different levels of per cent free prostate specific antigen (PSA) were derived from experience with consecutive Japanese male patients with intermediate total PSA values who underwent ultrasound-guided biopsies and/or transurethral resection of the prostate. Receiver operating characteristic (ROC) curve analysis showed that in patients with a total PSA of 4.1-10.0 ng/ml, per cent free PSA identified those with prostate cancer better than did total PSA; per cent free PSA also proved superior in the subgroup whose glands appeared benign on palpation. The probabilities of prostate cancer at per cent free PSA values of 10-15, >15-20, >20-26 and >26% were 58.3, 40.8, 25.3, 14.3 and 7.6%, respectively, when analyzed without regard to findings on palpation. In patients with palpably benign glands, the corresponding values were 55.3, 35.4, 19.6, 9.7, and 4.6%, respectively. These probabilities are lower than those reported in Western countries, probably reflecting both different patterns of practice and racial differences. Race-specific assessment is recommended before applying a clinical test.

Aged↗

PubMed2001

Neuronal nuclear alterations in dentatorubral-pallidoluysian atrophy: ultrastructural and morphometric studies of the cerebellar granule cells.

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease caused by a CAG repeat expansion, resulting in ubiquitinated inclusions and diffuse accumulation of mutant atrophin-1 in the neuronal nuclei in many regions of the central nervous system. In the cerebellar cortex, such nuclear abnormalities occur in the granule cells. In the present study, we performed ultrastructural and morphometric analyses on the nuclei of the cerebellar granule cells from eight patients with DRPLA (four with juvenile-onset disease and four with adult-onset disease) in an attempt to obtain further insight into the neuronal nuclear alterations that occur in CAG-repeat diseases. Ultrastructurally, all patients had intranuclear filamentous inclusions (NIIs, neuronal intranuclear inclusions) and nuclear membrane indentations (NMIs) in some of their granule cells, and chromatin tended to be sparse in the nucleoplasm of the affected nuclei. No such changes were observed in the granule cells of four control subjects. In all patients there was an association between NIIs and NMIs, and nuclei with NIIs and/or NMIs were larger than those without such changes. However, the nuclear enlargement was not due solely to the NIIs - even nuclei without NIIs or NMIs were larger in the patients than in the controls. In the DRPLA patients, there was a significant inverse correlation between the cross-sectional area of the nuclei and the disease duration. These findings indicate that NIIs and NMIs are features in the disease and occur in association with each other, and that nuclear enlargement - the degree of which may decrease with time after onset of the illness - is a more prevalent abnormality than the formation of NIIs or NMIs.

Adolescent↗

PubMed2001

Volume-weighted mean nuclear volume predicts tumor biology of clinically organ-confined prostate cancer.

BACKGROUND: Estimates of volume-weighted mean nuclear volume (MNV) are the only means by which unbiased estimates of three-dimensional parameters can be obtained from a single two-dimensional section, with stereological methods. The present study was conducted to elucidate the role of MNV in predicting tumor biology for patients treated with radical prostatectomy. METHODS: A retrospective prognostic study of 71 patients with T1/T2 disease, treated with radical prostatectomy alone, was performed. MNV was estimated using biopsy specimens based on a stereological method, and was compared with other preoperative clinical variables. For patients with prostate-specific antigen (PSA) failure, we determined the correlation of MNV with PSA doubling time (PSA DT) which was calculated using PSA values obtained with an ultrasensitive assay. RESULTS: Mean MNVs for pathologically organ-confined and non-organ-confined tumors were 198.9 and 236.3 microm3, respectively; this difference was significant (P = 0.0364). Univariate analysis showed that PSA, MNV, and Gleason score were significant predictors of prognosis (P = 0.0126, 0.0148, and 0.0375, respectively). Multivariate analysis revealed that MNV and preoperative PSA were powerful independent predictors of prognosis (P = 0.0160 and P = 0.0147, respectively), but the Gleason score was not correlated with prognosis (P = 0.4120). For patients with PSA failure, PSA DT was significantly correlated with MNV (r = -0.597, P = 0.0099). When these patients were classified using median PSA DT at 6 months into two groups, MNV was significantly greater in PSA rapid-riser group than in the slow-riser group (P = 0.0008), but no differences were observed between these groups in PSA, the Gleason score, or cancer volume. CONCLUSIONS: The findings of the present study suggest that MNV is a powerful predictor of PSA failure for patients with clinically organ-confined disease treated with radical prostatectomy. More importantly, they suggest that MNV can be a useful new parameter for prediction of tumor biology for patients with PSA failure after radical prostatectomy.

Aged↗

PubMed2001

Interleukin-18 (IL-18) synergizes with IL-2 to enhance cytotoxicity, interferon-gamma production, and expansion of natural killer cells.

We investigated the in vitro effects of combining interleukin-18 (IL-18) and IL-2 on human lymphocytes. The combined use of these two cytokines synergistically enhanced the proliferation, cytolytic activity, and interferon-gamma production of peripheral blood mononuclear cells. Phenotypic analysis revealed a preferential expansion of CD56+CD3- cells and an up-regulation of IL-2 receptor-alpha expression on natural killer cells. Isolated natural killer cells showed a substantial increase in proliferation and cytotoxicity compared with CD4+ and CD8+ T cells. The combined use of IL-18 and IL-2 should be considered a viable strategy to induce an antitumor response in vivo.

CD4-Positive T-Lymphocytes↗

PubMed2001

Trends in treatment for pancreatic cancer.

Although surgical resection is considered to be the only approach that offers a possibility of cure to patients with pancreatic cancer, the prognosis of the disease has not been improved markedly by any surgical procedures in the past 20 years. Large-scale randomized prospective clinical trials are being conducted in the United States and Italy, comparing standard lymph node dissection with extended lymph node dissection. Although preoperative chemoradiation has various advantages in the treatment of pancreatic cancer, it does not contribute to its downstaging and eventual cure. The combination of leucovorin, 5-fluorouracil (5-FU), and extracorporeal irradiation, however, has been proven to improve the patient's quality of life (QOL). Palliative surgery still requires further research in areas such as the examination of morbidity rates and the duration of bypass effects, now that laparoscopic and endoscopic surgery have both been well developed. Recent biological research has revealed the mechanisms of the carcinogenesis and the progression of pancreatic cancer, and, against this background, we assume that more effective trials will be conducted soon. Immunotherapy with dendritic cells, as well as gene therapy with mutant adenovirus, has already been employed clinically. Pancreatic cancer therapy is now facing new prospects.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Detection of prostate cancer by prostate-specific antigen.

The use of prostate-specific antigen (PSA) for early detection of prostate cancer has dramatically increased the reported incidence of this malignancy but its net benefit is unclear and remains controversial at present. Although several countries have adopted prostate cancer screening as a health policy, a reduction of cancer mortality would be an ultimate indication of the effectiveness of early detection. Since screening upon patient request cannot be refused, appropriate information should be provided until further support is available.

Adult↗

PubMed2001

Treatment outcome by risk group after radical prostatectomy in Japanese men.

BACKGROUND: North American investigators have suggested the usefulness of risk-group stratification based on prostate-specific antigen (PSA), clinical stage and biopsy Gleason score for predicting the biochemical outcome of prostate cancer after radical prostatectomy. There have been no reports of the application of this stratification to early biochemical outcome after radical surgery in Japanese men. METHODS: The study population consisted of 178 men treated with radical retropubic prostatectomy and bilateral pelvic lymph node dissection at Kitasato University Hospital (n = 110) and Kurashiki Central Hospital (n = 68) between October 1992 and May 1999. Pathologic and biochemical outcomes after radical prostatectomy were analyzed based on risk-group stratification. Risk groups were further analyzed according to detailed pathologic findings at biopsy. RESULTS: The median follow-up period for the 178 patients after radical surgery was 41.5 months (range, 2.0--82.0 months; mean, 40.9 months). Fifty-eight patients experienced PSA failure at a median of 8.0 months following surgery (range, 0.0--58.0). Risk-group stratification distinctly defined groups of pathologic findings in the radical prostatectomy specimens. The proportion of patients with PSA failure for low, intermediate and high-risk groups were 9.5%, 23.9% and 56.9%, respectively (P < 0.0001). Use of the number of cores with cancer and maximum cancer length in biopsy cores failed to improve risk stratification for PSA outcome in all risk groups. CONCLUSIONS: Risk-group stratification based on preoperative variables may significantly improve a physician's ability to counsel patients about PSA outcome after radical prostatectomy. Further improvement in risk stratification may call for use of variables other than the pathologic information in biopsy cores.

Aged↗

PubMed2001

The role of volume-weighted mean nuclear volume in predicting tumour biology and clinical behaviour in patients with prostate cancer undergoing watchful waiting.

OBJECTIVE: To investigate whether the volume-weighted mean nuclear volume (MNV, the only means by which unbiased estimates of three-dimensional variables can be obtained from a two-dimensional section by stereological methods) at diagnosis correlates with tumour biology and clinical behaviour in patients with prostate cancer treated by watchful waiting. PATIENTS AND METHODS: In a prognostic study, 64 patients with clinically localized prostate cancer were followed prospectively with initial expectant management. The median (mean, range) follow-up was 22 (27, 6.0-68) months. The prostate specific antigen (PSA) doubling time (PSADT) was calculated by linear regression. The MNV was estimated using biopsy specimens, based on a stereological method, and compared with PSADT and traditional clinicopathological variables. RESULTS: PSADT was significantly associated with MNV, but not with other clinicopathological variables. The PSA 'rapid-riser' subset (PSADT or=median value) and PSA-stable subsets (P = 0.0017 and 0.004, respectively). On multivariate analysis using a stepwise Cox proportional hazards regression, only MNV remained independently significant as a predictor of clinical progression among the clinicopathological variables (P < 0.001). CONCLUSIONS: These findings suggest that cancer cell nuclear volume is significantly associated with tumour biology and behaviour in patients with prostate cancer. Although further study with a larger patient population is needed to confirm the findings, estimates of MNV may be an important prognostic indicator in men treated with watchful waiting.

Age of Onset↗

PubMed2001

Retroperitoneoscopic radical nephrectomy by the posterior lumber approach for renal-cell carcinoma associated with chronic renal failure.

PURPOSE: To evaluate the efficacy and invasiveness of retroperitoneoscopic radical nephrectomy for renal-cell carcinoma (RCC) in patients with chronic renal failure (CRF), a group known to have relatively high surgical risk. PATIENTS AND METHODS: Between May 1996 and September 1999, six CRF patients maintained on hemodialysis underwent retroperitoneoscopic radical nephrectomy for clinically localized RCC by the posterior lumber approach. The excised kidneys were evacuated via a posterior skin incision (5 cm) between two port sites; the muscle layers were not incised. RESULTS: The procedure was completed in all patients with no major complications. The mean operative time was 162 (range 135-210) minutes, and the estimated blood loss was 58 (15-100) mL; none of the patients required a blood transfusion. Regular hemodialysis was restarted on postoperative day 2 or 3. CONCLUSIONS: This procedure seems to be minimally invasive and suitable for the treatment of small RCC in atrophic kidneys, especially in patients with CRF.

Atrophy↗

PubMed2001

A study of pretreatment nomograms to predict pathological stage and biochemical recurrence after radical prostatectomy for clinically resectable prostate cancer in Japanese men.

BACKGROUND: Accurate pretreatment identification of the risks that prostate cancer has extended beyond the gland and that it will recur would significantly influence practice patterns. Preoperative nomograms to predict such risks have not been developed for the oriental male population. METHODS: Construction of nomograms to predict preoperatively pathological outcome and early biochemical failure following radical prostatectomy in Japanese males was based on logistic regression analysis, with predicted probabilities and 95% confidence intervals for the final model being obtained by repeating the analysis on 1000 bootstrap samples from the original cohort. RESULTS: Prostate-specific antigen level, clinical stage and biopsy Gleason score contributed significantly to the prediction of pathological stage and of biochemical failure in the univariate analysis (p < 0.001). Combined use of these three variables predicted these treatment outcomes better than any single variable (p < 0.001). Nomograms combining these three variables to predict final pathological findings and early biochemical failure were then developed. The medians and 95% confidence intervals of the predicted probabilities are presented in the nomograms. CONCLUSIONS: This information enables clinicians to use their nomograms when counseling Japanese patients, leading to more informed treatment decisions and helping to identify those with a high risk of early biochemical failure. The nomograms may also be used to assure comparability of different treatment modalities in investigational trials.

Aged↗

PubMed2001

Toxicity and health-related quality of life during and after high dose rate brachytherapy followed by external beam radiotherapy for prostate cancer.

BACKGROUND: The optimal protocol for combining high dose rate brachytherapy and external beam irradiation as treatment for localized prostate cancer is unknown. Toxicity rates and clinical and biochemical outcomes should be evaluated to validate the current treatment protocol. METHODS: Fifty-eight patients were treated for prostate cancer with high dose rate brachytherapy followed by 30 Gy of external beam radiation therapy. Toxicity during treatment and for 12-18 months thereafter, and treatment-related morbidity, were evaluated. Physician-assessed treatment-related toxicity was graded at the time of occurrence using the Radiation Therapy Oncology Group morbidity criteria. Four separate self-administered questionnaires were used to collect longitudinally demographic data and general and prostate disease-related measures of quality of life. RESULTS: Various degrees of rectal bleeding due to radiation proctitis were experienced by 13 patients (22%) at a median time of 11 months. Two of these patients needed hospitalization to undergo laser coagulation of the rectal mucosa. Study patients had statistically significant decreases in five SF-36 domains during the first month of treatment. All measures recovered by 12 months. Sexual function was not affected by irradiation. Lower urinary tract symptoms assessed by IPSS/QOL scores worsened significantly during the first month of treatment but later recovered to baseline levels. Physician-assessed RTOG scores failed to detect these changes. CONCLUSIONS: Morbidity associated with combined radiation therapy was greatest during the first month of treatment and affected quality of life significantly. Most measures recovered to baseline levels by 12 months following radiation therapy. Although the current protocol appears acceptable, measures should be taken to decrease treatment-related morbidity further.

Adult↗

PubMed2001

Decline in the positive rate of human T-lymphotropic virus type-1 (HTLV-1) antibodies among blood donors in Nagasaki.

OBJECTIVE: The aim of this study was to clarify the trend of the HTLV-1 seroprevalence rate among blood donors. METHODS: Samples were screened by the particle agglutination test for HTLV-1 antibodies. MATERIALS: Serum from blood donors was screened. RESULTS: The positive rate of HTLV-1 antibodies among blood donors decreased from 13.14 to 0.81 % over the years from 1928 to 1983. CONCLUSION: A decline over the years in the positive rate of HTLV-1 antibodies among blood donors was revealed.

Adolescent↗