Ganglioside disialosyl globopentaosylceramide is an independent predictor of PSA recurrence-free survival following radical prostatectomy.

BACKGROUND: Disialosyl globopentaosylceramide (DSGb5) is a ganglioside originally isolated from renal cell carcinoma (RCC) tissue that has been associated with RCC metastasis. However, in prostate cancer, the expression of DSGb5 has not yet been fully assessed. In this study, we investigated DSGb5 expression in prostate tissues and the relationship between DSGb5 expression and clinicopathological characteristics of prostate cancer patients. METHODS: A total of 130 patients who underwent radical prostatectomy (RP) at our hospital between January 2005 and December 2007 were analyzed in this study. The expression of DSGb5 in prostatectomy specimens was examined by immunohistochemical analysis with monoclonal antibody 5F3 (anti-DSGb5). Associations between 5F3 expression and clinicopathological findings were investigated and the factors that affected PSA failure-free survival were assessed by Kaplan-Meier analysis and a Cox regression model. RESULTS: When immunoreactivities of 5F3 were measured, negative to strong staining was observed in prostate cancer tissue, whereas strong staining was observed in benign prostate glands. These expression patterns suggest that DSGb5 may act as a differentiation antigen in cancerization. The PSA failure-free survival was significantly higher in the 5F3 intact expression group than in the 5F3 reduced expression group (log-rank P=0.0220). On multivariate analysis, 5F3 intact expression showed significantly worse PSA failure-free survival following RP. CONCLUSIONS: 5F3 expression reflects the clinical and pathological features of prostate cancer and is correlated with the outcomes following RP. Further studies are necessary to clarify the functional roles of DSGb5 and establish a novel biomarker for prostate cancer.

Construction of mono- and bivalent human single-chain Fv fragments against the D antigen in the Rh blood group: multimerization effect on cell agglutination and application to blood typing.

An expression system for mono- and bivalent single-chain Fv fragments (scFv) of a human antibody against D antigen in the Rh blood group system was established in Escherichia coli. The cDNA encoding the Fv fragment of the anti-D monoclonal antibody D10 was cloned using the polymerase chain reaction and expressed in E.coli by fusing with a peptide tag link in the C-terminus of the light chain variable region. The scFv fragment expressed by the bacteria produced specific agglutination of human D positive red cells in the presence of an anti-peptide tag antibody. Flow cytometric analysis clearly indicated that the bacterially prepared scFv showed high specificity and affinity for D antigen, which was identical with that of the parental IgG. In order to construct bivalent D10 scFv for use in direct cell agglutination, the scFv was fused with a dimeric protein, bacterial alkaline phosphatase (BAP). The fusion protein produced significant agglutination of human red blood cells with D antigen, confirming that the bacterially expressed fusion protein is a functional bivalent antibody fragment. Specific agglutination of D positive red cells by D10 scFv-BAP was enhanced in the presence of anti-BAP antibody, suggesting that further multimerization of scFv led to highly efficient cell agglutination. By grafting BAP enzymatic activity into the scFv fragment (enzyme-linked scFv), blood typing could conveniently be performed. These results indicate that bacterially expressed scFv and scFv-BAP would be of practical use in blood typing. The system reported here could also be applied to the examination of other cell surface antigens and cell agglutination.

[Randomized-controlled study of treatment with UFT-MMC or UFT-ACR in advanced gastric cancer. Tohoku Study Group of Cancer Treatment for the Digestive Organs].

The effect of UFT-MMC- or UFT-ACR-therapy on the unresectable or recurrent gastric cancer was studied by a multicenter, randomized-controlled trial. All the patients who were randomly divided into the two groups were administered orally with 400 or 600 mg/day of UFT everyday. In addition, the UFT-MMC group was intravenously injected weekly for three weeks and then triweekly after six weeks with 6 or 8 mg/body of MMC, while the UFT-ACR group was intravenously injected with 20 mg/body of ACR for 5 serial-days every three weeks. Out of 88 cases registered, 75 (85.2%) were evaluable, consisting of 40 (31 complete cases) in UFT-MMC and 35 (27 complete cases) in UFT-ACR. There was no difference in various background factors between the two groups. PR, NC and PD was 10/31, 15/31 and 6/31 in the UFT-MMC group, whereas 0/27, 22/27 and 5/27 in the UFT-ACR group, respectively. The efficacy in the former group was higher, though not significant (U-test, p = 0.052), than that in the latter group. However, there was no difference in the 50% survival time (4.9 months in UFT-MMC vs. 5.4 months in UFT-ACR) of the either group.

Exfoliation as a mode of cancer elimination in rectal carcinoma.

A histopathological survey of surgical materials from 143 patients with rectal carcinoma subjected to chemotherapy and low-dose radiotherapy with tegafur and bleomycin was carried out. The chemotherapy combined with radiotherapy brought about better results than chemotherapy alone. In 4 of the 58 patients treated with radiochemotherapy, no cancer cells could be found in surgical specimens. Exfoliation into the rectal lumen of cohorts of cancer cells may occur in some cases of rectal carcinoma thus treated, resulting in cancer cell elimination.

[Phase III multi-center study of levamisole (LMS)--a randomized evaluation in advanced gastrointestinal cancer, with special reference to stomach cancer].

A randomized study of 5-FU + adriamycin (the control group) vs 5-FU + adriamycin + levamisole (LMS group) was conducted by an envelope method in 167 patients with advanced gastrointestinal cancer for clinical evaluation of LMS against advanced gastrointestinal cancer. There was a significant increase in survival with the LMS group (p less than 0.05). Median survivals were 3.7 months for the control group and 6.1 months for the LMS group of all patients with gastrointestinal cancer and patients with gastric cancer, respectively. There were no differences in response rate and duration of response between both groups, but the number of PD (progressive disease) cases was significantly smaller in the LMS group than in the control group (p = 0.001). Adverse reactions occurred more frequently in the LMS group, but there was no significant difference in incidence between both groups.

[Combined radiotherapy and chemotherapy for the treatment of esophageal cancer].

Eight patients with esophageal cancer were treated by a new treatment schedule consisting of low dose irradiation, crescendo cisplatin and bleomycin polyacrylate pasta. As monitored endoscopically, therapeutic responses were satisfactory: seven out of 8 patients have survived for a range of 3 to 20 months and still active at work or cancer-free. However, one patient suffered from a second malignancy of adenocarcinoma of the upper esophagus different from the initial squamous cell carcinoma at the lower esophagus which had successfully been treated 3 months before. The present therapeutic design aims at treatment of lymphatic spreads in the adjacent structures as well as the original tumor in the esophagus and submucosal invasions. It is basically a consecutive, multimodal integration of selective concentration of therapeutic effects (extensive radiotherapy, topical application of bleomycin polyacrylate pasta, lymphatic chasing with colloidal bleomycin, and spatial concentration of cisplatin as the result of radiation-induced inflammation), perpetuation of the repairable DNA damage, and biological amplifications (protection against esophageal perforation with polyacrylate coating, and specific cancer cell recruitment). Application of the present therapeutic design is being expanded to the treatment of cancer of other specific sites such as the head and neck tumors and rectal cancer with undeniable prospects.

Mucosal secretion of the duodenum in peptic ulcer disease.

Mucosal secretin content of the duodenum was measured using bioptic specimen in healthy controls and patients of peptic ulcer. Immunoreactive secretin in the duodenal mucosa was found greater in healthy controls (7.73 +/- 2.71 ng/mg dry wt., mean +/- S.D.) than in gastric ulcer patients (5.76 +/- 3.51 ng/mg dry wt.) and duodenal ulcer patients (5.54 +/- 2.48 ng/mg dry wt.), but the difference was not significant. There was no significant relationship between mucosal secretin and acid output in these patients.

Effect of p-hydroxyphenyl-propionic ester of tranexamic acid hydrochloride (Cetraxate) on peptic ulcer. Multi-center clinical study.

The therapeutic effects of a new antiulcer drug, a p-hydroxyphenyl-propionic ester of tranexamic acid (cetraxate, CET) hydrochloride, were investigated in 234 patients with gastric ulcer by double blind controlled study using trans-3,7-dimethyl-2,6-octadienyl-5,9,13-trimethyltetradeca-4,8,12-trienoate (gefarnate) as the standard drug in 18 medical institutions. The cure rates confirmed by endoscopic examination in CET-treated patients were 28, 61 and 73% each after 4, 8 and 12 weeks of medication, while those in gefarnate-treated patients were 23, 47 and 55%, respectively, with statistical significance after 8 and 12 weeks. Global utility rate based on the judgement by the physician in charge also supported the results with cure rate. Stratified analysis again confirmed the superiority of CET hydrochloride against gefarnate in the hospitalized patients in terms of both cure rate and global utility rate. However, there was no significant difference between the two drugs as to the effects in the out-patients. Among the symptoms, there was also a significant difference between the improvement rate of epigastralgia with the two drugs in favour of CET hydrochloride. No serious side effects were reported throughout the study.

[The upper gastrointestinal imaging and the gastrogram using 99mTc-pertechnetate (author's transl)].

99mTc-pertechnetate was used for the diagnoses of the upper gastrointestinal tract. Oral administration was useful for the detection of the stenosis and obstruction on the esophagus and the pylorus to the poor risk patients. Mucosal imaging of the stomach was clearly revealed by intravenous administration, and the scintigram of the patient with stomach cancer showed a cold region. Taking the gastric scintiphoto, temporal radioactivity in the stomach region was recorded (gastrogram). This seems to be a new and prospective approach to the clinical gastroenterology.