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Biomedical subjects

N Sawabu

Publications and source records attributed to N Sawabu.

At least 73 records · Page 4Linked to original sources

Detection of K-ras point mutation at codon 12 in pure pancreatic juice collected 3 years and 6 months before the clinical diagnosis of pancreatic cancer.

We report herein a patient with K-ras point mutation at codon 12 that had been detected in pure pancreatic juice (PPJ) obtained 3 yr and 6 months before he was diagnosed with pancreatic cancer (PC). In this 73-yr-old man, PC was diagnosed by ERCP, which showed obstruction of the main pancreatic duct (MPD) at the borderline area between the body and tail of the pancreas. Distal pancreatosplenectomy was performed, and an advanced PC at the tail of the pancreas with a few metastatic nodules in the liver was confirmed. Retrospectively, a K-ras point mutation at codon 12 from GGT (glycine) to GAT (aspartic acid) was detected in the PPJ collected endoscopically 3 yr and 6 months earlier, as well as in the PPJ when PC was diagnosed and in the resected tumor tissue. Reevaluation of pancreatography from the ERCP performed at that time revealed a very mild stenotic lesion of the MPD, speculated to be a PC at a very early stage, at the body-tail border, but it was difficult to diagnose this lesion as a PC, based only on this morphological study. Accordingly, we believe that this is an interesting and valuable clinical case, indicating that K-ras mutation can precede clinical evidence, and its determination in PPJ could be a useful genetic test calling for a careful and extensive clinical investigation for early detection of PC.

Adenocarcinoma↗

The human pancreatitis-associated protein (PAP)-encoding gene generates multiple transcripts through alternative use of 5' exons.

The nucleotide (nt) sequence of the human cDNA encoding PAP, a pancreatic secretory protein induced during acute pancreatitis, was found to be identical with that of a gene activated in human primary hepatocellular cancer, designated HIP. To obtain insight into the expression of PAP/HIP, we characterized the gene organization, especially focusing on the 5'-flanking region, and found that it spans about 3 kb and is composed of six exon. Exon 1 encodes the 5'-noncoding sequence and exon 2 consists of three miniexons, 2a, 2b and 2c; the common exon 2c encodes the sequence including the start codon. Analysis by RT-PCR revealed the presence of at least three different types 5'-ends of human PAP/HIP transcripts which were derived from alternative use of 5'-exons. Although all three types of transcripts were expressed in both normal small intestine and pancreas, their gene expression was increased ectopically in gastric cancer, hepatocellular cancer and pancreatic acinar cell carcinoma. Furthermore, significant differences among the transcript types were detected between normal and tumor tissues, and especially between gastric and hepatocellular cancers, suggesting that PAP/HIP expression may vary with differences in 5'-alternative splicing.

Alternative Splicing↗

Measurement of serum PSP/reg-protein concentration in various diseases with a newly developed enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay, based on two monoclonal antibodies (Hreg1-1 and Hreg101-1) specific for pancreatic stone protein (PSP)/reg-protein, was developed to determine the concentration of this protein in serum from individuals with various diseases. The serum concentration of PSP/reg-protein was significantly higher in patients with various pancreatic diseases than in normal controls, and was also significantly higher in patients with acute pancreatitis or chronic relapsing pancreatitis than in patients with chronic pancreatitis. Furthermore, the serum PSP/reg-protein concentration was also significantly increased in liver cirrhosis, choledocholithiasis, and various cancers of the digestive system, and was extremely high in all patients tested with chronic renal failure. A significant correlation was apparent between the serum concentration of PSP/reg-protein and elastase-I in 68 patients with chronic pancreatitis or pancreatic cancer. Whereas only 7 of these patients showed a normal serum PSP/reg-protein concentration and a significantly increased elastase-I concentration, 15 of these patients showed a significantly increased serum PSP/reg-protein concentration and a normal serum elastase-I concentration. These results indicate that the serum PSP/reg-protein concentration may reflect pancreatic damage, especially in acute pancreatitis, and may be a sensitive a marker for such damage as elastase-1, although false positivity was apparent in renal failure and in some patients with hepatic dysfunction or digestive system malignancies.

Antibodies, Monoclonal↗

Endosonographic evaluation of giant gastric folds.

Giant gastric folds develop in several benign and malignant diseases. We used endoscopic ultrasonography to evaluate giant gastric folds in 15 patients with Borrmann type IV scirrhous carcinoma, 8 patients with gastric lymphoma, 5 patients with anisakiasis, 1 patient with Menetrier's disease, and 6 normal subjects with simple gastric hyperrugosity. With a 7.5 MHz transducer, a five-layered gastric wall structure was imaged. The thickness of the gastric wall and each layer was measured and compared with the endosonographic findings of 16 healthy subjects. Endoscopic ultrasonography findings revealed that the second layer alone was thickened in Menetrier's disease, and the third layer alone enlarged in anisakiasis. Most of the patients with scirrhous carcinoma showed an abnormally enlarged third and fourth layer. The second layer together with the third layer was thickened in healthy subjects with simple hyperrugosity and also in patients with gastric lymphoma. However, the fourth ultrasound layer corresponding to the muscularis propria was significantly thickened only in malignant conditions. It is concluded that endoscopic ultrasonography can visualize the structure of giant gastric folds and may facilitate the differentiation of benign from malignant etiologies.

Adenocarcinoma, Scirrhous↗

Endosonography of a submucosal tumor-like gastric lesion caused by fibrotic ulcer healing.

A 61-year-old woman with a gastric antral ulcer scar had a lesion that showed a submucosal tumor-like appearance on endosonography, which proved at resection to represent dense submucosal fibrous tissue. The reason for this marked reaction has not yet been established. Although we felt that the endosonographic pattern most likely showed submucosal fibrosis, in view of her past medical history, malignant lymphoma or aberrant pancreas could not be ruled out with certainty.

Endoscopy, Gastrointestinal↗

Comparison of lansoprazole and famotidine for gastric ulcer by endoscopic ultrasonography: a preliminary trial.

To compare the efficacy of lansoprazole and famotidine in the treatment of gastric ulcer, 24 patients with gastric ulcer were treated for 8 weeks. They were assessed by endoscopic ultrasonography (EUS), which provides cross-sectional images of the gastric wall as well as endoscopic images. Patients were randomly assigned to receive either lansoprazole 30 mg once daily (n = 12), or famotidine 20 mg twice daily (n = 12). The healing rate after 4 weeks of treatment was 80% in the lansoprazole group and 40% in the famotidine group. After 8 weeks of treatment, the respective healing rates were 100 and 72.7%. Healing to Sakita's S2 stage of scarring occurred significantly more often in the lansoprazole group than in the famotidine group after 4 weeks (50% vs. 0%; p < 0.05). After 4 weeks of treatment, the submucosal fibrous tissues detected by EUS were significantly less extensive in the lansoprazole-treated patients with deep ulcers (reaching the muscle layer or serosa) than in the famotidine-treated patients with deep ulcers (p < 0.01). These results suggest that lansoprazole may be more effective in ulcer healing than famotidine, particularly in patients with deep gastric ulcers.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Effect of liu-junzi-tang on the symptom of bitter taste in patients with chronic gastritis.

A symptom of bitter taste was found in 15 out of 82 patients with chronic gastritis that was diagnosed from symptoms and endoscopic findings. Liu-junzi-tang was very effective in 12 (80%) of the 15 patients. The symptom of bitter taste completely disappeared in 24.7 days on average after oral administration of Liu-junzi-tang in these 12 patients. In the remaining 3 patients, the symptom of bitter taste did not completely disappear, but was improved. Other symptoms associated with chronic gastritis and endoscopic findings were also improved in these patients. These findings indicate that Liu-junzi-tang may be a good remedy for the symptom of bitter taste in patients with chronic gastritis.

Adult↗

Endoscopic therapy for early gastric cancer. Utility of endosonography and evaluation of prognosis.

We analyzed 30 endoscopically treated patients with early gastric cancer in terms of the utility of endoscopic ultrasonography (EUS) and the evaluation of prognosis. Endoscopic therapy for early gastric cancer included strip biopsy, laser irradiation, and OK-432 injection. Examination of the depth of cancer invasion in the strip biopsy specimens showed that the diagnostic accuracy of EUS was 85.7%. Complete resection rate in strip biopsy was 82.8%, and the patients with incompletely resected cancer were successfully treated with laser irradiation and/or OK432 injection. The prognosis of the patients treated with strip biopsy was good. Three patients died of causes other than gastric cancer. Local recurrence and a heterochronous new lesion developed in six patients, but all of these cases were successfully treated with additional strip biopsy. All but one patient treated with laser irradiation and/or OK 432 injection survived during the study period. These results suggest that EUS is useful in determining the indication of endoscopic therapies and that prognosis is good in patients with early gastric cancer treated endoscopically.

Aged↗

[Isoenzyme as tumor marker].

Expression of cancerous isoenzymes in various malignant tumors has been extensively studied using different biochemical techniques. Cancerous alkaline phosphatase (ALP) isoenzymes such as variant ALP and placental ALP are apparently detected in sera or tissues from patients with malignant tumors. Variant ALP is a specific tumor marker for hepatocellular carcinoma (HCC). Placental ALP is found in sera of patients with various malignant diseases. However, the positive rate of each ALP isoenzyme is low except for high positivity of placental ALP in seminoma. Novel gamma-glutamyltranspeptidase (gamma-GTP) isoenzyme is specifically found in about 60% of sera from patients with HCC, but in only 3% of patients with benign liver diseases, suggesting high specificity for HCC. Serum prostatic acid phosphatase (PAT), which increases in activity in parallel with the growth of prostatic tissue, is an useful marker for prostatic cancer. Thus, several cancerous isoenzymes are available for diagnosis of various malignant tumors.

Biomarkers, Tumor↗

[Mutation of the K-ras oncogene in pancreatic carcinoma, and application of its detection in pancreatic juice to diagnose pancreatic carcinoma].

The incidence of the point mutation of K-ras oncogene at codon 12 in surgical or autopsy specimens of pancreatic carcinoma (PC) is reportedly extremely high ranging from 75 to over 90%, and the K-ras mutation found in PC is almost exclusively present in codon 12. The GGT to GAT transition of the 12th codon is observed in more than 50% of PC of Japanese patients, although the incidences of transition of GGT to CGT, GTT, and GAT are essentially equal in PC of European countries. With this point in mind, the authors attempted to detect K-ras mutations in DNA obtained from pancreatic juice (PJ) collected endoscopically. K-ras mutations at codon 12 were found in 55% of 20 PC patients by PCR and ASO probe hybridization method, and in 80% of 25 PC patients by PCR-RFLP method. On the other hand, K-ras mutations were negative in PJ from chronic pancreatitis with one exception by PCR-RFLP method. Other authors also reported almost the same results. These results suggest that analysis of K-ras oncogene in PJ can be useful for qualitative diagnosis of PC, and would be expected as a novel tool for early detection of PC.

DNA, Neoplasm↗

Antitumor effects of saikosaponins, baicalin and baicalein on human hepatoma cell lines.

Antitumor effects of nine components of a herbal medicine, 'Sho-saiko-to', were investigated on human hepatoma cell lines (PLC/PRF/5, Hep-G2), human liver cells (Chang) and a human pancreatic cancer cell line (BxPC-3). The concentration of each component required for 50% inhibition of cell growth of PLC/PRF/5 cells was as follows: saikosaponin-d, baicalin, 20 micrograms/ml; saikosaponin-a, baicalein, 50 micrograms/ml; saikosaponin-b2, -c, ginsenoside-Rb1, -Rg1, glycyrrhizin, > 1000 micrograms/ml. Saikosaponin-a in 50-micrograms/ml quantities inhibited the cell growth and DNA synthesis of all the cell lines tested. These results indicate that 'Sho-saiko-to' includes potent antitumor components such as saikosaponin-a, -d, baicalin against human hepatoma cells as well as other human cell lines.

Antineoplastic Agents↗

Serum levels of c-erbB-2 protein in digestive diseases.

The clinical significance of the measurement of c-erbB-2 oncogene product was evaluated. The subjects consisted of 404 patients, including 248 with cancer of the digestive organs and 128 with benign digestive diseases. Serum c-erbB-2 protein levels were measured by sandwich immunoenzyme assay. The positive rates of c-erbB-2 protein, at a cut-off value of 17.0 U/ml, were, for cancers: hepatocellular carcinoma 61.6%, biliary tract cancer 54.8%, pancreatic cancer 25.0%, esophageal cancer 33.3%, gastric cancer 16.9%, and colorectal cancer 5.0%. For benign digestive diseases, the rates were: liver cirrhosis 63.3%, chronic hepatitis 43.2%, acute hepatitis 42.9%, other liver diseases 42.8%, cholelithiasis 30.0%, and chronic pancreatitis 0%. Serum c-erbB-2 protein levels were significantly correlated with the markers of hepatic functional reserve, the indocyanine green retention rate and the hepaplastin test. These findings suggest that serum c-erbB-2 protein levels are greatly influenced by liver dysfunction and that their clinical usefulness as a serum tumor marker is questionable.

Adult↗

Aberrant hepatic duct connected with the main pancreatic duct by anomalous pancreato-biliary ductal union: case report.

An aberrant hepatic duct directly connected to the main pancreatic duct with anomalous arrangement of the pancreato-biliary ductal system is reported here, the first report of such a case, to our knowledge. A 53-year-old woman was admitted to our hospital because of cholecystolithiasis with abdominal pain in the right upper quadrant. Endoscopic retrograde cholangiopancreatography (ERCP) showed that an aberrant hepatic duct, which independently drained the right posterior segment of the liver, connected to the main pancreatic duct at a high insertion site distal to the sphincter area of the major papilla. The common bile duct (containing stones), on the other hand, united with the main pancreatic duct in a normal fashion. Cholecystectomy and bile duct lithotomy were performed. The aberrant hepatic duct was separated from the main pancreatic duct just above the junction, and was anastomosed side-by-side to the common hepatic duct. The embryologic development of this lesion is not clear, but is discussed in this report.

Anastomosis, Surgical↗

Measurement of sialylated stage-specific embryonic antigen-1 in pure pancreatic juice for the diagnosis of pancreatic cancer.

The diagnostic significance of measuring sialylated stage-specific embryonic antigen-1 (SLX) in pure pancreatic juice was evaluated in 20 patients with pancreatic cancer, 43 with chronic pancreatitis, 13 with cholecystolithiasis, and 15 control individuals. Four fractions of pure pancreatic juice were collected sequentially from the pancreatic duct by endoscopic cannulation. The SLX levels in all four fractions of pure pancreatic juice were significantly higher in patients with pancreatic cancer than in controls. On the other hand, patients with chronic pancreatitis or cholecystolithiasis did not have SLX levels that significantly differed from those of controls in any fraction. When the cut-off value was set as the mean concentration +2 times the standard deviation of the control values, the positive rates of SLX in the first fraction (washout phase) and the third fraction (secretory phase) of pure pancreatic juice from pancreatic cancer were 55% (11/20) and 40% (8/20), respectively. Although the false positive rates in the first fraction were high in chronic pancreatitis (30%) and cholecystolithiasis (31%), such high SLX levels in the third fraction were found only in one (2%) patient with chronic pancreatitis and in one (8%) with cholecystolithiasis. The specificities of the test for pancreatic cancer in the first fraction and the third fraction were 70% (39/56) and 96% (54/56), respectively. These results indicate that the measurement of SLX in the third fraction of pure pancreatic juice is useful as a specific marker for pancreatic cancer.

Chronic Disease↗