Molecular pathogenesis of viral hepatitis.
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Dendritic Cells↗
Biomedical subjects
Norio Hayashi
Publications and source records attributed to Norio Hayashi.
[Successful treatment for renal cell carcinoma with lung metastases by interleukin-2 and interferon-alfa: a case report].
We report a case in which a regimen of interleukin-2 (IL-2) and interferon alfa (IFN-alpha) was effective against renal cell carcinoma with lung metastases. A 69-year-old man diagnosed with right renal tumor had not received treatment for 28 months. He was admitted to our hospital for treatment. Computed tomographic (CT) findings showed a right renal tumor 11.5 cm in diameter and multiple lung metastases. Right nephrectomy was performed, and pathological examination was renal cell carcinoma (clear cell carcinoma, G2, pT3a). A regimen of IL-2 and IFN-alpha was selected as an adjuvant therapy. He received 70 x 10(4) JRU/day of IL-2 (div) 5 times a week, and 600 x 10(4) IU/day of IFN-alpha intramuscularly 3 times a week for 8 weeks. Thereafter, both treatments were continued 3 times a week. CT scan showed a complete response on lung metastases 12 months and no recurrence has been observed on CT scan for 16 months after operation.
Aged↗
[Treatment results of radical prostatectomy in clinical stage B and C prostate cancer: comparison of the neoadjuvant therapy group versus the surgery group; retrospective analysis of 80 cases].
Between 1994 and 2001, 80 patients underwent radical prostatectomy without adjuvant therapy for clinical stage B and C prostate cancer. The patients were not treated with adjuvant therapy before biochemical prostate specific antigen (PSA) failure. Of all 80 patients, 35 patients (43.8%) received neoadjuvant hormonal therapy prior to radical prostatectomy (the neoadjuvant therapy group), 45 patients (56.2%) underwent prostatectomy alone (the surgery alone group). Retrospective analysis to evaluate the effects of neoadjuvant therapy was performed from clinicopathological findings and the biochemical PSA failure-free rate. Of all patients, 58 (72.5%) were in clinical stage B and 22 (27.5%) were in clinical stage C. Of 58 patients in clinical stage B, 19 (32.8%) underwent prostatectomy combined with neoadjuvant therapy. Of the 22 patients in clinical stage C, 17 (77.3%) underwent prostatectomy combined with neoadjuvant therapy. Pathologically, 37 (46.3%) were in stage B, 38 (47.5%) in stage C and 2 (2.5%) in stage D1. Three patients in the neoadjuvant therapy group had no malignant findings in specimens of prostatectomy. In comparison with the clinical stage, pathologically 8 (22.9%) showed overstaging, 4 (5.0%) understaging and 23 (28.8%) accurate staging in the neoadjuvant therapy group, respectively, 0 (0.0%), 20 (44.4%), and 25 (55.6%) in the surgery alone group. In clinical stage B and C, there was no significant difference in the biochemical PSA failure-free rate between the neoadjuvant therapy group and the surgery alone group. On the other hand, in pathological stages B, the 5-year PSA failure-free rate was 63.2% in the neoadjuvant therapy group, but 100% in the surgery alone group. Although neoadjuvant therapy may have some effect on downstaging, our retrospective analysis suggests that it has no significant effect on PSA failure-free rate.
Antineoplastic Agents, Hormonal↗
[A case of long-term survival with TAE resistant multiple recurrence HCC successfully treated by hepatic resection].
A 55-year-old female was admitted to our hospital for a third recurrence of hepatoma. She was treated with transcatheter arterial embolization (TAE) in April and November 1996. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed multiple tumors of S4/S8 and S7 in the liver. After the third TAE using SMANCS, Lipiodol and Spongel, abdominal CT revealed insufficient Lipiodol retention and the in efficacy of this treatment. A right lobectomy of the liver was performed for the TAE resistant multiple recurrence of HCC. After the surgery, the patient survived for over 5 years with no recurrence. It appears that this surgery may be a useful modality for TAE resistant multiple recurrence hepatoma in cases of good liver function and lesions limited to the hemi lobe.
Antineoplastic Agents↗
[Prospect for the 21st century. The digestive organs].
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Forecasting↗
An enzymatic method of analysis for GDP-L-fucose in biological samples, involving high-performance liquid chromatography.
To investigate the biological significance of GDP-L-fucose, we established a unique method for the determination of GDP-L-fucose levels in microsomal fractions, using an HPLC assay of alpha 1-6-fucosyltransferase (alpha1-6-FucT), an enzyme that catalyzes the synthesis of core fucosylation in N-glycans. A microsomal protein and a large excess of fluorescence-labeled synthetic oligosaccharide (a substrate) were incubated with a large excess of alpha1-6-FucT. The fluorescent intensity of the fucosylated reaction product, which was analyzed by isocratic reverse phase HPLC, was proportional to the level of GDP-L-fucose in the microsomal fractions over the range 0.20-10 pmol. This assay is applicable to the determination of the GDP-L-fucose content in various cancer cell lines as well as rat liver and would be useful in developing a better understanding of the fucosylation potential of such cells and tissues.
Aminopyridines↗
[Molecular physiopathology of viral hepatitis].
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Dendritic Cells↗
Cyclooxygenase-2 activity altered the cell-surface carbohydrate antigens on colon cancer cells and enhanced liver metastasis.
Cyclooxygenase-2 (COX-2) was recently reported (M. Tsujii and R. N. DuBois, Cell, 83: 493-501, 1995) to affect the metastatic potential of cells. Previous studies (M. Fukuda, Cancer Res., 56: 2237-2244, 1996) indicated that sialyl Lewis antigen expression is correlated with hematogenous metastasis of colon cancer. In the present study, we investigated the interaction between COX-2 activity, expression of sialyl Lewis antigens, in vitro cancer cell adhesion to endothelial cells, and in vivo metastatic potential. Effects of COX-2 activity and prostaglandin E(2) on cell adhesion, expression of sialyl Lewis antigens, and glycosyltransferase genes were determined in Caco-2-m (COX-2 low level), Caco-2-COX-2 (programmed to overexpress COX-2), and HT-29 (COX-2 high level) cells. Metastatic spread of these cells to the liver was also investigated. Caco-2-COX-2 cells had increased SPan-1 levels and increased adherence to endothelial cells via SPan-1 compared with Caco-2-m cells. HT-29 cells expressed sialyl Lewis a and adhered to endothelial cells via sialyl Lewis a. Treatment with a COX-2 inhibitor, celecoxib, decreased SPan-1 and sialyl Lewis a expression and adherence to endothelial cells. beta 3Gal-T5 and ST3Gal III and IV expression was inhibited by celecoxib and was enhanced by prostaglandin E(2) treatment. Caco-2-COX-2 and HT-29 cells metastasized to the liver, whereas Caco-2-m cells did not. Pretreatment with celecoxib reduced the metastatic potential as well as anti-sialyl Lewis antibodies. Our results indicate a direct link between COX-2 and enhanced adhesion of carcinoma cells to endothelial cells, and enhanced liver metastatic potential via accelerated production of sialyl Lewis antigens. COX-2 inhibitors may suppress metastasis.
Animals↗
Serum HCV RNA levels during early phase of recombinant interferon alfa-2a (Roferon A) therapy for chronic hepatitis C and efficacy of short-term therapy with earlier loss of viremia.
We conducted a prospective, controlled, multicenter trial to assess if earlier changes of serum HCV RNA levels were predictable for long-term effect, and if a short-term therapy was effective in such patients. All 377 chronic hepatitis C (CH-C) patients were treated with interferon (IFN) daily 9 MU for 4 weeks. Patients positive for HCV RNA at week 1 were treated with IFN three times weekly for additional 22 weeks (group A), while those negative for HCV RNA were randomized into either regimens; three times weekly for another 22 (group B) or 12 weeks (group C). When complete responders (CR) were defined as the subjects showing sustained loss of viremia with therapy, CR rates were 17.7% (25/141) for group A, 80.0% (36/45) for group B and 61.0% (36/59) for group C, respectively. Group B showed a significantly higher CR rate than group C, indicating that a 16-week treatment period was inadequate. Patients with CR showed a rapid decrease in virus levels by day 2 after starting therapy. The CR ratio in patients with HCV RNA levels of <1.0 Kcopy/ml by day 2 was 64.6% (82/127), while the ratio without <1.0 Kcopy/ml was 12.7% (15/118). CR ratio in patients who became negative by week 2 was 65.7%, whereas only 2.9% after week 2. The results indicate that the determination of HCV RNA levels at day 2 and the qualitative assay at week 2 with IFN are useful in predicting the therapeutic effect.
Journal Article↗
Preoperative predictors of cancerous involvement of the neurovascular bundles in patients with localized prostate cancer.
BACKGROUND: The purpose of this study was to identify preoperative variables that would be useful in objectively selecting prostate cancer patients for nerve-sparing prostatectomy. METHODS: Twenty-six patients with clinical T1c-T2c cancers were evaluated for cancerous involvement in the region of the neurovascular bundles (NVB) from prostatectomy specimens. Preoperative prostate-specific antigen (PSA) and pathologic features in systematic biopsy specimens also were reviewed. RESULTS: A total of eight (31%) patients had cancerous involvement in the region of the NVB, including four on the right side, three on the left side and one on both sides. The percentage of each biopsy specimen occupied by the cancer was scored from zero to four and defined as the positive biopsy score. Preoperative PSA (P = 0.046), mean positive biopsy score (total sum of positive biopsy score divided by number of biopsy specimens; P = 0.001), number of cores containing cancer (P = 0.011), percentage of cores involved (P = 0.036) and maximum positive biopsy score (P < 0.001) were significant for predicting cancerous involvement in the NVB region using univariate analysis. However, only the mean positive biopsy score was independently significant according to multivariate analysis. To predict cancerous involvement in the region of each NVB, we found that ipsilateral mean positive biopsy score (total sum of corresponding positive biopsy score divided by number of ipsilateral biopsy specimens), number of cores involved on the ipsilateral side, percentage of cores involved on the ipsilateral side and maximum positive biopsy score on the ipsilateral side were significant predictive variables: the ipsilateral mean positive biopsy score being most appropriate for clinical practice. CONCLUSION: Ipsilateral mean positive biopsy score in systematic biopsy specimens can be an appropriate variable for selecting patients with localized prostate cancer for nerve-sparing prostatectomy.
Aged↗
Tumor necrosis factor alpha stimulates invasion of Src-activated intestinal cells.
BACKGROUND & AIMS: Src activation is correlated with progression of colorectal cancer (CRC). CRCs accompanied by ulcerative colitis, chronic inflammation in the colon, often have elevated Src activity, and ulcerative colitis-related CRCs are more likely to become invasive, whereas Ras activation is rarely associated with this disease. The aim of this study was to investigate the effects of a proinflammatory cytokine, tumor necrosis factor alpha (TNF-alpha), on the invasive properties of epithelial cells constitutively expressing activated Ras or Src. METHODS: A cell line derived from intestinal epithelia was transfected with a v-src- or v-H-ras-expressing vector. The effect of TNF-alpha on morphologic changes in colonies cultured in soft agar was determined. Src protein kinase activity, peroxide production, E-cadherin expression levels, and the phosphorylation status of beta-catenin and E-cadherin were determined. The invasive potential of these cells was determined by measuring cell motility and using an in vitro invasion assay. RESULTS: TNF-alpha altered the colony morphology of src-, but not ras-expressing cells. TNF-alpha increased peroxide production, leading to Src protein expression as well as Src activity in src transfectants. Activation of Src by TNF-alpha led to reduced E-cadherin levels and enhanced invasion of src transfectants. Pyrrolidine dithiocarbamate and herbimycin A inhibited these effects. CONCLUSION: These results indicate that Src kinase activation enhances the response of epithelial cells to TNF-alpha leading to increased invasion through mechanisms that involve production of reactive oxygen intermediates.
Agar↗
Interferon for decreasing the incidence of hepatocellular carcinoma in patients with chronic hepatitis C.
The incidence of hepatocellular carcinoma (HCC) in Japan has kept increasing during the past few decades. Persistent infection with hepatitis C virus (HCV) is the single most frequent cause of HCC in Japan at present. Interferon is the only reliable means of eradicating HCV infection, and by inference, preventing HCC associated with it. Since interferon is not effective in all the patients with chronic hepatitis C, it needs to be used with utmost discretion. The incidence of HCC is decreased not only in the patients who respond to interferon completely, accompanied by the loss of HCV RNA from serum, but also in those who obtain normal levels of aminotransferase while HCV persists after interferon. The patients who poorly respond to interferon need to be treated by other means of suppressing necroinflammatory processes in chronic hepatitis C, which is expected to retard the development of HCC.
Antiviral Agents↗
Quick generation of fully mature dendritic cells from monocytes with OK432, low-dose prostanoid, and interferon-alpha as potent immune enhancers.
Dendritic cells (DCs) are one of the promising tools for enhancing antigen-specific immune responses in clinical settings. Many studies have been performed thus far to verify the efficacy of the DC vaccine in cancer patients; however, the responses have not always been satisfactory, partly because of DC incompetence. To obtain DCs potentially applicable for vaccination of cancer patients, our group sought to establish the strategy of DC generation mainly by modulating culture periods and maturation stimuli. Novel mature DCs that can be generated from monocytes within 3 days by using a combination of OK432 (Streptococcus pyogenes preparation), low-dose prostaglandin E2 (PGE2), and interferon-alpha (OPA-DCs) were developed. They strongly express CD83, CD86, and CCR7 and have potent ability to migrate to CCL21. In addition, they were able to activate natural killer and T helper 1 (TH1) cells and to induce peptide-antigen-specific cytotoxic T lymphocytes more significantly than monocyte-derived DCs stimulated with a conventional cytokine cocktail of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and PGE2 (monocyte-conditioned medium [MCM]-mimic DCs). The profound ability of OPA-DCs to stimulate these effectors is attributable to their higher expression of IL-12p70, IL-23, and IL-27 than MCM-mimic DCs, which was supported by the findings that the neutralization of IL-12p70 and IL-23 reduced the TH1 priming ability of OPA-DCs. Even when from advanced gastric or colonic cancer patients, OPA-DCs displayed abilities of migration and TH1 induction comparable to those from healthy subjects. Therefore, OPA-DCs may serve as a feasible vaccine with the potential to enhance TH1-dominant and cytolytic immune responses against cancers.
Adjuvants, Immunologic↗