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Biomedical subjects

M Onda

Publications and source records attributed to M Onda.

At least 73 records · Page 4Linked to original sources
PubMed2000

New target region of allelic loss in hepatocellular carcinomas within a 1-cM interval on chromosome 6q23.

BACKGROUND/AIMS: Frequent allelic losses on the long arm of chromosome 16 in several types of human cancers have suggested that 16q harbors one or more genes that are important for suppressing tumorigenesis in the tissues in question. METHODS: To identify the locations of putative tumor suppressor genes involved in hepatocellular carcinoma, we examined 96 primary hepatocellular carcinomas for their patterns of allelic loss at 18 microsatellite marker loci distributed along this chromosome arm. RESULTS: Allelic loss at one or more loci was observed in 48 (50%) of these tumors. The highest frequency of loss of heterozygosity (42%) was observed with marker D6S311 on chromosome 6q23. Through detailed deletion mapping of tumors having partial or interstitial deletions, we identified two commonly deleted regions at 6q23 and at 6q26-27. CONCLUSIONS: The common region at 6q23 lay within a 1-cM interval, flanked by D6S977 and D6S311. The previously documented deletion region that includes the M6P/IGF2R locus was confined to a 20-cM region at band 6q26-27 in our panel of tumors. The location we defined at 6q23 for a putative suppressor of hepatocellular carcinoma has not been reported before.

Adult↗
PubMed2000

Multiple primary malignant neoplasms in patients with esophageal cancer.

This study aims to elucidate the incidence and the therapeutic and prognostic implications of co-existent non-esophageal primary malignant neoplasms in patients with esophageal cancer. Between 1974 and 1997, 33 patients with esophageal cancer treated at the Nippon Medical School Hospital were documented as having multiple primary malignant neoplasms (MPN). The therapeutic strategies and post-therapeutic survival of these patients were retrospectively investigated. Among 291 patients with esophageal cancer, 33 patients (11.3%) were also found to have non-esophageal primary malignant neoplasms. Twenty patients (60.6%) had synchronous MPN and 13 (39.4%) had metachronous MPN. Among the MPN, apart from esophageal cancer, gastric (32.6%) and head and neck cancer (32.6%) were the most common. The incidence of esophageal cancer occuring in association with cancers of the head and neck or gastric cancer was high. Frequent examination in these cancer patients, using fiberoptic esophagogastric endoscopy for example, may be helpful in the early diagnosis of esophageal cancer.

Aged↗
PubMed2000

Effect of angiostatin on liver metastasis of pancreatic cancer in hamsters.

The liver is the most common site of metastasis in pancreatic cancer, and there are no promising strategies to treat it. Angiostatin, a kringle-containing fragment of plasminogen, is a potent inhibitor of angiogenesis. The effect of angiostatin on liver metastasis in pancreatic cancer was investigated by using our established hamster model of liver metastasis. Pancreatic cancer cells (PGHAM-1, 1 x 10(6)) derived from N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic tumor in Syrian golden hamsters were transplanted into the spleen of female hamsters, and the animals were subcutaneously injected with angiostatin and saline. Subsequently, the macroscopic appearance of liver surface metastases was evaluated. In addition, histological sections of the liver metastases were analyzed for neovascularization, proliferation, and apoptosis on the basis of von Willebrand factor, argyrophilic nucleolar organizer region (Ag-NOR), and TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, respectively. The results showed significant tumor growth retardation and inhibition of angiogenesis in metastatic liver tumors in response to treatment with angiostatin. Moreover, the metastases remained in a nearly dormant state due to a balance between apoptosis and proliferation of the tumor, with no detectable side effects. This is the first experimental trial of angiostatin on pancreatic cancer and liver metastasis. The results suggest that angiostatin therapy could be effective against liver metastases of pancreatic cancer.

Angiogenesis Inhibitors↗
PubMed2000

Establishment and characterization of two new rectal neuroendocrine cell carcinoma cell lines.

BACKGROUND: Human colorectal neuroendocrine cell carcinoma (NEC) is a rare disease with a poor prognosis. The biological behavior of NEC remains poorly understood. MATERIALS AND METHODS: We established two new NEC cell lines from a patient with rectal neuroendocrine carcinoma, NECS-P and NECS-L from the primary tumor and a liver metastasis, respectively. We investigated the biological differences between the two cell lines to study the mechanisms involved in liver metastasis. RESULTS: There was no difference between NECS-P and NECS-L in the morphological, ultrastructural and immunohistochemical studies. After addition of TGF-beta(1), the doubling times of NECS-P were increased in a dose-dependent manner relative to untreated cells, whereas TGF-beta(1) had no effect on NECS-L. The attachment and chemotactic response of the two cell lines were not enhanced by TGF-beta(1). The invasive capacity and the production of matrix metalloproteinase-2 (MMP-2) were significantly increased only in NECS-L following the addition of TGF-beta(1). When anti-MMP-2 antibody was added to the medium with TGF-beta(1), NECS-L invasion was inhibited. CONCLUSION: It is considered that these differences are important to understand the mechanisms of liver metastasis of NEC.

Carcinoma, Neuroendocrine↗
PubMed2000

Detection of circulating anti-p53 antibodies in esophageal cancer patients.

It has been reported that circulating anti-p53 antibodies (p53-Ab) in the serum are detected in some cancers. To investigate the usefulness of detecting p53-Ab, we measured the circulating p53-Ab in comparison with squamous cell carcinoma antigen (SCC-Ag) in patients with esophageal carcinoma. Serum specimens from 46 esophageal cancer patients (42 squamous cell carcinomas, 3 mucoepidermoid carcinomas and 1 basaloid squamous carcinoma) and 13 healthy subjects were studied. Serum p53-Ab was measured by an enzyme-linked immunosorbent assay. Surgically resected specimens from 43 patients were immunohistochemically stained for p53. Serum SCC-Ag was measured by a radioimmunoassay. The results were analyzed with the clinical data and outcome. Serum p53-Ab was detected in 13 (28%) of the 46 patients, but not in any of the healthy subjects. The positive rate was 0% (0/6) in stage I, 60% (3/5) in stage IIA, 30% (3/10) in stage IIB, 29% (7/24) in stage III and 0% (0/1) in stage IV. There was no difference in the outcome between the p53-Ab-positive and p53-Ab-negative patients. Immunohistochemically, 30 (70%) of the 43 specimens stained positively for p53. Serum p53-Ab was detected in 43% (13/30) of the patients with tumors which stained positively for p53. There was a close correlation between positivity for p53 immunostaining and positivity for p53-Ab (p<0.01). An elevated level of SCC-Ag was found in only 13%of the patients, and most patients positive for SCC-Ag already had advanced disease with lymph node metastasis and invasion to the adventitia. In conclusion, serum p53-Ab was detected in Japanese esophageal cancer patients at a frequency similar to that reported in Western countries. Serum p53-Ab may be a potentially useful molecular marker for detection and screening of esophageal cancer. Further studies of a large population may be required to elucidate the true diagnostic usefulness of measuring the serum p53-Ab.

Aged↗
PubMed2000

Proliferating cell nuclear antigen and p53 protein expression in submucosal invasive colorectal carcinoma.

In some cases of early colorectal carcinoma, radical surgical resection might be required because of vessel invasion, distant metastasis, or inadequate surgical margin. To characterize submucosal invasive colorectal carcinoma, we investigated expression of PCNA and p53 protein. Sixty-seven patients who underwent curative resection of submucosal invasive colorectal carcinoma participated in this study. The PCNA labeling index (PCNA-LI) is determined at the deepest lesion of carcinoma. The expression of PCNA and p53 protein were analyzed according to clinicopathological factors. 1) The PCNA-LI was correlated to histological grade, depth of invasion or vessel invasion in polypoid type. 2) The flat type had significantly higher PCNA-LI (65.1+/-8.2%) and p53 protein expression (69.6%) than the polypoid type. 3) The PCNA-LI was higher in cases with lymph node metastasis than in these without lymph node metastasis. 4) Overexpression of the p53 protein was detected in all cases with liver metastasis. Our results suggest that in order to determine the treatment for the patients with submucosal invasive colorectal carcinoma, the expression of PCNA and p53 protein may be a useful biologic marker.

Aged↗
PubMed2000

Successful removal of a stone and an expandable metallic stent from the biliary tract of a patient with acute occlusive pyogenic cholangitis.

We removed a biliary stone and the metallic stent placed two years previously in a patient with benign biliary strictures. An 80-year-old woman who had been inplanted with an expandable metallic stent (EMS) to prevent obstruction by a large common bile duct stone about two years before as an emergency measure in another hospital, was afficted with acute occlusive pyogenic cholangitis (AOPC) and hospitalized in our hospital. After treating the AOPC, we successfully removed the EMS with a cholangioscope and normal biopsy forceps through the percutaneous transhepatic channel under fluoroscopy. The type of the EMS was Accufulex stent. To remove it was easier than expected. Once it started to unravel, it was removed from the common bile duct within a few minutes.

Acute Disease↗
PubMed2000

Primary leiomyoma of the pancreas.

We report the first documented case of a primary leiomyoma of the pancreas. A 72-yr-old female patient was admitted to our hospital for the follow-up of a pancreatic tumor detected 2 yr previously at a different hospital. Diagnostic images revealed the presence of a tumor located in the head of the pancreas. The tumor was characterized by a clear margin, hypervascularity, and was a homogenous mass. Moreover, the tumor had not changed in size or characteristics since a previous computed tomography (CT) scan performed 2 yr previously. The tumor was preoperatively diagnosed as a nonfunctional islet-cell tumor or papillary cystic tumor. During the operation, the tumor was found to be encapsulated and showed no signs of direct invasion to neighboring structure. Tumorous lesions of the liver or swellings of the neighboring lymph nodes suggesting metastasis were not found. Instead of a pancreatoduodenectomy, the tumor was enucleated. Microscopically, immunohistochemical studies of a resected specimen indicated a myogenic origin, and neither mitotic activity nor hemorrhagic and necrotic findings were recognized. No signs of recurrence have been seen since its excision. Accordingly, the tumor was diagnosed as a primary leiomyoma of the pancreas.

Aged↗
PubMed2000

[Liver transplant aspiration cytology to monitor the intragraft events].

Liver transplant aspiration cytology(TAC) contributes significantly to the differential diagnosis of transplanted liver graft dysfunction, since each of the possible causes induces characteristic cytological findings in the graft and peripheral blood. That is, TAC can differentiate various inflammatory changes as indicating acute rejection, viral infection, or bacterial infection. The key is the intensity of activated lymphocytes in the graft and in blood. Remarkable lymphocytic activation only in the liver graft indicates acute rejection, meanwhile in a case of viral infection the activation can be seen both in liver graft and blood. The patterns and degree of liver cell injury and cholestasis can also identify the reason for liver impairment. Several cases of acute rejection, viral infection, and subclinical acute rejection diagnosed by TAC were recognized on TAC slide preparations. Subclinical rejection, which means acute rejection appreciated only cytologically or histologically, can be followed without treatment unless the patient demonstrates jaundice and liver enzymes over 100 units. In a case of chronic rejection, TAC is not an appropriate method of diagnosis, because there are few infiltrating cells in the portal triad, and subsequently, no visible activated lymphocytes on TAC slides. Although TAC is not well accepted, it is an informative means preliminary to core biopsy, and its use is expected to become wide-spread in the future because it is a safe procedure with minimal invasiveness to patients, and useful for differential diagnosis. The use of TAC will lessen the frequency of performing more invasive core biopsy.

Adolescent↗
PubMed1999

Tob2, a novel anti-proliferative Tob/BTG1 family member, associates with a component of the CCR4 transcriptional regulatory complex capable of binding cyclin-dependent kinases.

Human cDNAs encoding a novel member of Tob/BTG1 anti-proliferative family proteins were cloned. The putative protein product termed Tob2 consisted of 344 amino acids with high similarity to the Tob protein. The tob2 mRNA was 4.1 kb long and was ubiquitously expressed in human adult tissues, as was revealed by Northern blot hybridization. However, further in situ hybridization analysis showed a characteristic expression of the tob2 mRNA in oocytes, suggesting a unique role of Tob2 in oogenesis. Like the Tob protein, Tob2 inhibited cell cycle progression from the G0/G1 to S phases. Intriguingly, the amino-terminal half of Tob2 as well as that of Tob was associated with a human homologue of yeast Caf1, a component of the CCR4 transcription factor complex. Moreover, Caf1 was associated with cyclin dependent kinases. These data suggested that both Tob and Tob2 were involved in cell cycle regulation through their interaction with Caf1. Finally, the tob2 gene was mapped to human chromosome 22q13.1-q13.31.

3T3 Cells↗
PubMed1999

Reduction of the nonspecific animal toxicity of anti-Tac(Fv)-PE38 by mutations in the framework regions of the Fv which lower the isoelectric point.

Anti-Tac(Fv)-PE38, also called LMB-2, is a very active recombinant immunotoxin that has produced eight responses, including a durable clinical complete remission in a recently completed phase I trial of leukemias and lymphomas. Dose escalation was limited by liver toxicity. We have noted that the Fv of anti-Tac has an isoelectric point (pI) of 10.2. We hypothesize that the overall positive charge on the Fv portion of anti-Tac(Fv)-PE38 contributes to nonspecific binding to liver cells and results in dose-limiting liver toxicity. We have used a mouse model to investigate the basis of this toxicity and found that lowering the pI of the Fv of anti-Tac from 10.2 to 6. 82 by selective mutation of surface residues causes a 3-fold decrease in animal toxicity and hepatic necrosis. This change in pI did not significantly alter the CD25 binding affinity, the cytotoxic activity toward target cells, or antitumor activity, resulting in a 3-fold improvement in the therapeutic index. If this decreased toxicity occurs in humans, it should greatly increase the clinical utility of this immunotoxin.

ADP Ribose Transferases↗
PubMed1999

Somatic mutation of the PTEN/MMAC1 gene in breast cancers with microsatellite instability.

The extent to which microsatellite instability (MI) contributes to the etiology of breast cancer has not been established in any large-scale studies. We examined 528 samples of tumor DNA from patients with primary breast cancer for MI, using 14 polymorphic CA-repeat markers. The frequency of MI in these tumors was unexpectedly low (10/528, 1.9%). The ten MI+ tumors were analyzed for mutations in five potential target genes that contain simple repeat sequences (TGFBIIR, IGF2R, hMSH6, BAX and PTEN/MMAC1). A somatic insertion of an extra adenine in the (A)6 region at codon 321-323 (exon 8) of the PTEN/MMAC1 gene, leading to a frame-shift, was identified in one tumor. This observation represented the first documented instance of PTEN/MMAC1 alteration in a MI+ primary breast cancer.

Breast Neoplasms↗
PubMed1999

The usefulness of conducting investigations on intra-abdominal bacterial contamination in digestive tract operations.

A bacteriological study of 108 cases of gastrointestinal surgery was conducted by analyzing intra-abdominal bacterial contamination (IABC) and postoperative surgical site infections (SSI). We utilized an anaerobic porter to detect intra-abdominal bacterial infection and transport bacteria to the laboratory. The positive IABC rate was 42.9% for gastric cancer surgery, 22.6% for biliary tract surgery, and 85.7% for colorectal cancer surgery. Most cases of SSI were IABC-positive, and isolated bacterial species from the SSI were similar to those from the IABC. In colorectal cancer surgery, a preoperative chemical intestinal preparation and the prophylactic use of antibiotics had a major influence on the sensitivity of bacteria isolated from the SSI. These data suggest that prophylactic antibiotics should be chosen from among those to which bacteria from the IABC are highly sensitive, and that therapeutic antibiotics should be chosen from among those to which bacteria isolated from the SSI are highly sensitive. Finally, the exploration of IABC enables us to predict the incidence of SSI.

Adult↗
PubMed1999

Serum level of cytokeratin 19 fragment (CYFRA 21-1) indicates tumour stage and prognosis of squamous cell carcinoma of the oesophagus.

To determine the clinical efficacy of serum concentration of cytokeratin 19 fragment (CYFRA 21-1), sera from 66 patients with oesophageal squamous cell carcinoma were examined, and 54 surgically resected specimens were immunohistochemically stained for cytokeratin 19 (CK-19). The patients with positive CK-19 staining in the tissues of their carcinomas had significantly higher serum CYFRA 21-1 levels compared with those with negative CK-19 staining. When the cut-off value was defined as 2.0 ng/mL, CYFRA 21-1 had a higher positive ratio than that of either squamous cell carcinoma antigen (SCC-Ag) or carcinoembryonic antigen (CEA). Serum CYFRA 21-1 level increased significantly along with the clinical stages. In addition, serum CYFRA 21-1 level served as a prognostic factor for patients with oesophageal carcinoma after surgery, whilst SSC-Ag and CEA is not connected with the outcome. These findings suggest that the serum CYFRA 21-1 probably originated from the tumour tissue is an important marker for determining the stage and outcome of oesophageal carcinoma.

Adult↗