Biomedical subjects

M Monden

Publications and source records attributed to M Monden.

At least 19 recordsLinked to original sources

PubMed2006

Expression of PPARdelta in multistage carcinogenesis of the colorectum: implications of malignant cancer morphology.

Whether peroxisome proliferator-activated receptor (PPAR) delta is a good target for the chemoprevention and/or treatment of colorectal cancer (CRC) remains controversial. Our goal was to examine PPARdelta expression in multistage carcinogenesis of the colorectum and to assess the relevance of PPARdelta in CRC. Immunohistochemical analysis indicated that PPARdelta expression increased from normal mucosa to adenomatous polyps to CRC. In cancer tissues, the PPARdelta protein was accumulated only in those cancer cells with highly malignant morphology, as represented by a large-sized nucleus, round-shaped nucleus, and presence of clear nucleoli. Interestingly, the cancer tissue often contained both PPARdelta-positive and -negative areas, each retaining their respective specific morphological features. Moreover, this pattern persisted even when PPARdelta-positive and -negative cells were aligned next to each other within a single cancer nest or gland and was present in the majority of CRC cases. Immunohistochemistry for Ki-67 proliferation marker showed no significant correlation between Ki-67 and PPARdelta in CRC samples. Based on Western blot analysis and quantitative RT-PCR, high PPARdelta protein expression correlated with high PPARdelta mRNA levels. Peroxisome proliferator-activated receptor delta may have a supporting role in tumorigenesis, and the close association between PPARdelta expression and malignant morphology of CRC cells suggests a pivotal role in cancer tissue.

Adenocarcinoma↗

PubMed2006

Risk factors for graft dysfunction after adult-to-adult living donor liver transplantation.

The aim of this study was to investigate the risk factors for graft dysfunction after adult-to-adult living donor liver transplantation (LDLT). Thirty-nine adults with chronic cirrhosis underwent LDLT between 1999 and 2004. Their postoperative courses were uneventful with no vascular or bile duct complications early after LDLT, except one mild hepatic artery stenosis. The preoperative MELD scores were significantly higher in the failed graft group (n=5) than the functioning graft group (n=34; P=.004), while the graft liver weight/standard liver volume ratio was similar between these groups. We concluded that a high preoperative MELD score was associated with postoperative graft failure and that graft size had little impact on graft outcome. Although large grafts would seem intuitively more suitable for sick recipients, we did not show a benefit among this cohort; the MELD score was the best predictor, a finding that is also most consistent with donor safety.

Adult↗

PubMed2006

Alpha-fetoprotein mRNA detection in peripheral blood for prediction of hepatocellular carcinoma recurrence after liver transplantation.

The aim of this study was to assess the value of alphafeto protein (AFP) mRNA-expressing cells detected in peripheral blood for predicting tumor recurrence after living donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC). The test group consisted of 25 patients who underwent LDLT for end-stage liver disease with HCC while the control group consisted of 37 living donors. Quantitative real-time reverse-transcriptase polymerase chain reaction was used for detection of AFP mRNA-expressing cells in peripheral blood. Nine (36%) of 25 patients developed tumor recurrences (four lung; one liver; one peritoneum; two bone; one adrenal gland) during the follow-up period. Perioperatively, AFP mRNA was positive in peripheral blood of eight patients (32.0%) but only in 1 (2.7%) of the control. Preoperative AFP mRNA was positive in three cases. Univariate analyses revealed that preoperative and perioperative AFP mRNA and microscopical vascular invasion were the significant predictors for HCC recurrence (P = .007, .037, and .005, respectively). In the patients with HCC exceeding Milan criteria (n = 15), the presence of AFP mRNA-positive cells in the peripheral blood correlated significantly with HCC recurrence (P = .033). We concluded that the presence of AFP mRNA-expressing cells could be a useful predictor of HCC recurrence in liver transplant patients.

Adult↗

PubMed2006

Expression and mutation of SMAD4 in poorly differentiated carcinoma and signet-ring cell carcinoma of the colorectum.

Poorly differentiated adenocarcinoma (Por) and signet-ring cell carcinoma (Sig) are rare but highly malignant types of colorectal cancer. To explore their genetic backgrounds we investigated TGF-beta type II receptor (TGF-beta RII) and SMAD4 in the TGF-beta signaling pathway, and to identify their mutator phenotype we examined microsatellite instability (MSI) status. Loss of SMAD4 expression was significantly more frequent in Por (12 of 38; 31%) and Sig (4 of 5; 80%) tumors than in well (Well) and moderately differentiated (Mod) carcinomas (p = 0.04, 0.003, respectively). Mutation of the SMAD4 gene was detected in 2 of 26 Por tumors. MSI was positive in 14 of the 38 Por tumors and in 1 of the 5 Sig tumors, but in none of the Well or Mod tumors examined. We also found mutation of TGF-beta RII, a putative target of MSI, in 10 of 35 Por tumors (28.6%), but in none of 3 Sig tumors. As a whole, about 50% of the Por tumors and 80% of the Sig tumors showed abnormalities of either TGF-beta RII or SMAD4 expression. This suggests that disruption of the TGF-beta signaling pathway may play a central role in the pathogenesis of Por and Sig tumors of the colorectum.

Adenocarcinoma↗

PubMed2005

Treatment of hepatocellular carcinoma with major portal vein thrombosis by combined therapy with subcutaneous interferon-alpha and intra-arterial 5-fluorouracil; role of type 1 interferon receptor expression.

We previously reported the beneficial effects of combination therapy of interferon (IFN)-alpha/5-fluorouracil (FU) for advanced hepatocellular carcinoma (HCC) with tumour thrombi in the major portal branches. This report describes the results of longer follow-up and includes more than double the number of patients relative to the original report, and evaluates the role of IFN-alpha/type 2 interferon receptor (IFNAR2) expression on the response to the combination therapy. The study subjects were 55 patients with advanced HCC and tumour thrombi in the major branches of the portal vein (Vp3 or 4). They were treated with at least two courses of IFN-alpha/5-FU without major complication. In the 55 patients, 24 (43.6%) showed objective response (eight (14.5%) showed complete response, 16 (29.1%) partial response), four (7.3%) showed no response, and 27 (49.1%) showed progressive disease. Immunohistochemically, IFNAR2 expression was detected in nine out of 13 (69.2%) patients. There was significant difference in the time-to-progression survival (P = 0.0002) and the overall survival (P < 0.0001) between IFNAR2-positive and -negative cases. There was a significant correlation between IFNAR2 expression and response to IFN-alpha/5-FU combination therapy in univariate analysis (P = 0.0070). IFN-alpha/5-FU combination therapy is a promising modality for advanced HCC with tumour thrombi in the major portal branches and could significantly depend on IFNAR2 expression.

Adult↗

PubMed2005

Cyber visual training as a new method for the mastery of endoscopic surgery.

BACKGROUND: We devised a new method incorporating cyber visual training whereby novices in endoscopic surgery are instructed via repetition of a video-recorded procedure. We then conducted a study designed to investigate the impact of this cyber visual training on the mastery of intracorporeal knot-tying as an endoscopic technique. METHODS: For the cyber visual training a 10-min video of the same procedure was replayed at normal, slow, and rapid speeds or presented in a series of still images. The training was undertaken by 36 medical students and 1st year trainee doctors who had had no experience of endoscopic surgery. They were divided into three groups, each of all received the same introductory lecture. Group A was only given training with the instructor for 15 min. Group B trained with the instructor for 15 min and was allowed self-training for 10 min. Group C viewed the cyber video beforehand and then underwent training with the instructor for 15 min. For all participants, the time required to complete a knot-tying task was measured and the level of endoscopic skill before and after the training was assessed using a virtual reality system the minimally Invasive Surgical Trainer-Virtual Reality (MIST-VR), in terms of the following three parameters: time, errors, and efficiency of hand movements. The Steel-Dwass test was used to evaluate the differences among the three groups in task performance. RESULTS: Group C completed the knot-tying task faster than group A (p = 0.0375), but there were significant differences between groups A and B and groups B and C. There were no significant differences in the parameters assessed using the MIST-VR. CONCLUSIONS: Our new concept of cyber visual training is effective for mastering the knot-tying technique. This type of training should be widely applicable to other procedures, such as dissection, clipping, and hemostasis.

Adult↗

PubMed2005

Feasibility of autonomic nerve-preserving surgery for advanced rectal cancer based on analysis of micrometastases.

BACKGROUND: Autonomic nerve preservation has been advocated as a means of preserving urinary and sexual function after surgery for rectal cancer, but may compromise tumour clearance. The aim of this study was to determine the incidence of micrometastasis in the connective tissues surrounding the pelvic plexus. METHODS: The study included 20 consecutive patients who underwent rectal surgery with bilateral lymph node dissection for advanced cancer. A total of 78 connective tissues medial and lateral to the pelvic plexus and 387 lymph nodes were sampled during surgery. All connective tissue samples and 260 lymph nodes were examined for micrometastases by reverse transcriptase-polymerase chain reaction (RT-PCR) after operation. All patients were followed prospectively for a median of 36.0 months. RESULTS: Of 245 histologically negative lymph nodes, 38 (15.5 per cent) were shown by RT-PCR to harbour micrometastases. However, micrometastases to tissues surrounding the pelvic plexus were detected in only two (3 per cent) of 78 tissues, that is in two of 20 patients. Clinical follow-up showed that the two patients had a poor prognosis owing to distant metastases. CONCLUSION: Autonomic nerve-preserving surgery may be feasible for advanced rectal cancer, but study of more patients positive for micrometastases is required.

Adult↗

PubMed2005

Clinical usefulness of oral granisetron hydrochloride for alleviation of delayed nausea and vomiting induced by CPT-11.

This open label pilot study evaluated the safety and efficacy of the oral 5-HT3 receptor antagonist granisetron for prophylaxis of delayed chemotherapy-induced nausea and vomiting (CINV) in 30 patients with advanced or recurrent colorectal cancer. Patients were studied during two cycles of a 5-week regimen with irinotecan (CPT-11) and UFT. Patients received prophylactic anti-emetic therapy that included intravenous granisetron. If Grade 1 or higher severity gastrointestinal symptoms occurred during 6 days after CPT-11 administration in Cycle 1, then oral granisetron was administered daily for the following 5 days of CPT-11 in Cycle 2. Sixteen patients (53.3%) experienced delayed CINV in Cycle 1. The incidence of Grade 2 or higher vomiting was 32.1% and 27.7% in Cycles 1 and 2 in males (P = 0.554) respectively, and 54.6% and 32.4% in females (P = 0.001) respectively. Granisetron is effective against delayed Grade 2 or higher vomiting induced by CPT-11/UFT in female patients, although granisetron alone may not sufficiently control nausea induced by this regimen.

Administration, Oral↗

PubMed2004

Expression level of valosin-containing protein (VCP) as a prognostic marker for gingival squamous cell carcinoma.

BACKGROUND: Valosin-containing protein (VCP) is associated with anti-apoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. In the present study, association of VCP expression with prognosis of gingival squamous cell carcinoma (GSCC) was examined. PATIENTS AND METHODS: VCP expression in 74 patients with GSCC (34 males and 40 females) with ages ranging from 42 to 85 (median 66) years was evaluated by immunohistochemistry, in which staining intensity in tumor cells was categorized as either weaker (level 1) or equal to/stronger (level 2) than that in the endothelial cells. RESULTS: Twenty-four (32.4%) cases showed level 1 and 50 (67.6%) level 2 VCP expression. Patients with level 1 GSCC showed a significantly better 5-year survival rate than those with level 2 GSCC (5-year overall survival: 100% versus 84.9%, P < 0.05). Multivariate analysis revealed VCP expression level, lymph node metastasis and pT(TNM) to be independent factors for overall survival. Patients with GSCC at stages I and II showed favorable prognosis regardless of VCP expression status, whereas at stages III and IV, patients with level 1 VCP expression showed better survival rates than those with level 2 expression. CONCLUSION: Prognostic significance of VCP expression level in GSCC was demonstrated.

Adenosine Triphosphatases↗

PubMed2004

PCR-array gene expression profiling of hepatocellular carcinoma.

Many trials using DNA microarrays have been reported for various human malignancies, but an efficient molecular diagnostic system has yet to be established. Here, we adopted a high throughput quantitative PCR-array system based on adaptor-tagged competitive PCR (ATAC-PCR), as a novel technique for gene expression profiling of hepatocellular carcinoma (HCC). This PCR-array contained 3,072 genes derived from three different cDNA libraries, including 298 additional known genes suspected to be involved in hepatocarcinogenesis. Using this PCR-array with 20 pairs of liver tissues (20 HCC, 20 surrounding nontumor liver), we identified a total of 117 genes differing in expression levels in the two liver tissues. Hierarchical clustering analysis and principal component analysis with these genes revealed distinct gene expression patterns in the HBV-positive group and the HCV-positive groups. Among 117 genes, only 7 (GPAA1, TMEM9, FACL4, ADFP, MAWBP, PACE4, FOS) were common to both groups. In conclusion, this PCR-array analysis with an appropriate set of genes is considered useful for gene expression profiling of HCC, and we identified some genes which may play a common key role in hepatocarcinogenesis.

Aged↗

PubMed2004

Identification of differentially expressed genes involved in colorectal carcinogenesis using a cDNA microarray.

To identify candidate genes involved in human colorectal carcinogenesis, we constructed the gene expression profiles of 50 colorectal cancers (CRCs) and 12 normal colorectal epithelia using a cDNA microarray specially constructed for CRC. Hierarchical clustering analysis and principal component analysis could clearly distinguish the gene profiles of cancer tissues from those of normal tissues. Our results confirm there are indeed differences in gene expression between cancer and normal mucosa. Our cDNA microarray identified 22 up-regulated genes and 32 down-regulated genes in CRC. Many of these genes have been previously identified in relation to human carcinogenesis, 68% and 78%, respectively. Subsequent validation of selected genes by serial analysis of gene expression and reverse transcription polymerase chain reaction, demonstrated expression patterns that were almost identical to our microarray analysis. Using a four-fold larger sample relative to that used in our previous study, candidate genes involved in human colorectal carcinogenesis were reproducibly identified. Further studies of comprehensive gene expression using our technique may elucidate the mechanism of CRC tumorigenesis.

Cell Line, Tumor↗

PubMed2003

Laparoscopic lymph node dissection for gastric cancer with intraoperative navigation using three-dimensional angio computed tomography images reconstructed as laparoscopic view.

BACKGROUND: Laparoscopic extended lymph node dissection for gastric cancer is difficult to perform because it requires dissection with preservation of vessels. Therefore, an intraoperative navigation system for the angioarchitecture would be helpful. Recent enhanced volume-rendering computed tomography (CT) can produce clear intraluminal three-dimensional (3D) images. This advanced radiological technology can provide 3D angiographic images reconstructed in the same view as would be observed from a laparoscope inserted into the abdominal cavity. We report our experience with laparoscopic gastrectomy with radical lymph node dissection using this advanced radiological technology. METHODS: 3D CT angiographic images from the celiac axis to the proper hepatic artery were reconstructed in two ways preoperatively. The first was only 3D angiographic images that were reconstructed as the laparoscopic view (LapView 3D CT angiography). The second was LapView 3D CT angiography with images of the body of the pancreas, which was more useful for intraoperative navigation in comprehensing anatomy. Two monitors were placed over the shoulder of the patient during surgery. One monitor, which was controlled by the image mixer, projected the laparoscopic images with picture in picture of 3D CT angiographic images. The surgeon performed the surgery with reference to this monitor during lymph node dissection. RESULTS: 3D angiographic CT clearly showed all vessels of interest in laparoscopic lymph node dissection for gastric cancer in 10 cases. The anatomy of vessels appeared as if looking beyond visible surface. LapView 3D CT angiography was useful for laparoscopic navigation surgery.

Adult↗

PubMed2003

Laparoscopic intragastric surgery for gastric tube cancer following esophagectomy.

As a result of the recent improvement of the prognosis of esophageal cancer, the reporting frequency of gastric tube cancer following esophageal cancer has increased. Gastric tube total resection following median sternotomy, a highly invasive surgical procedure, is applied to the cases of advanced gastric tube cancer, whereas endoscopic mucosal resection is selected for the cases of early gastric tube cancer. If endoscopic mucosal resection is not applicable for some reason, partial or total resection of the gastric tube following median sternotomy has been selected. We applied laparoscopic intragastric surgery to such a case: The patient, a 59-year-old man with esophageal cancer, had undergone subtotal esophagectomy followed by gastric tube reconstruction through the retrosternal route 6 years before. Since endoscopy revealed early gastric cancer in the body of the stomach, we tried to perform mucosal resection but failed because of anastomotic stenosis. However, we successfully performed intragastric surgery, in which a camera and forceps were inserted directly into the gastric tube. Thus, laparoscopic intragastric surgery is a useful technique in cases to which endoscopic mucosal resection is not applicable.

Anastomosis, Surgical↗

PubMed2002

Locally expressed CTLA4-Ig in a pancreatic beta-cell line suppresses accelerated graft rejection response induced by donor-specific transfusion.

AIMS/HYPOTHESIS: This study examined whether locally expressed CTLA4-Ig can suppress the accelerated islet allograft rejection that is induced by donor-specific transfusion. METHODS: CTLA4-Ig-transfected or parental MIN6 cells were transplanted subcutaneously into the right flank of streptozotocin-induced diabetic C3H/Hej mice with or without donor-specific transfusion. For donor-specific transfusion, spleen cells from C57BL/6 mice were injected i.v. at the time of transplantation. In other experiments, CTLA4-Ig-transfected and parental MIN6 cells were transplanted separately into each flank, together with donor-specific transfusion. Rejection was defined as a blood glucose concentration of more than 300 mg/dl in two consecutive measurements, and graft survival was confirmed by hyperglycaemia after the grafts were removed. The effect of an anti-CTLA4 antibody on the survival of CTLA4-Ig-transfected MIN6 cells was also examined. RESULTS: In 7 of 12 donor-specific transfusion sensitised mice, CTLA4-Ig-transfected MIN6 cells remained viable 20 days after grafting, whereas all parental MIN6 cells ( n = 10) were rejected promptly, within 14 days. The prolonged allograft survival was observed even in the absence of detectable levels of serum CTLA4-Ig, while the surviving allografts continued to produce CTLA4-Ig in situ. This protection was abrogated by an anti-CTLA4 antibody, but not by a control antibody. Furthermore, six animals that maintained normoglycaemia after the separate transplantation of parental and CTLA4-Ig-transfected MIN6 cells into each flank all showed abrupt hyperglycaemia after the CTLA4-Ig/MIN6 graft was removed, suggesting that this protection operated locally. CONCLUSION/INTERPRETATION: A beta-cell line genetically engineered to secrete CTLA4-Ig can protect a graft locally from the alloimmune response induced by donor-specific transfusion.

Abatacept↗

PubMed2002

Prediction of the response to chemoradiation and prognosis in oesophageal squamous cancer.

BACKGROUND: The sensitivity of cancer cells to chemotherapy and radiation therapy depends on various biological properties. This study investigated the expression of p53, CDC25B and metallothionein (MT), and evaluated their clinical significance in chemoradiation therapy (CRT) for oesophageal squamous cell carcinoma. METHODS: The expression of p53, CDC25B and MT was evaluated by immunohistochemistry using biopsy specimens taken before CRT for 77 patients with oesophageal squamous cell carcinoma, and correlated with the pathological effects of CRT and survival. RESULTS: p53-positive tumours and MT-positive tumours had a poor response to CRT, whereas tumours with strong CDC25B expression were associated with a good response. When each patient was scored for the presence of the three biological factors, there was a strong correlation between the sensitivity score and the pathological effect of CRT (P < 0.001), and a (non-significant) difference in the 5-year survival rate between patients with a high score and those with a low score (67 versus 34 per cent respectively; P = 0.12). CONCLUSION: The combined evaluation of p53, CDC25B and MT may help to identify patients with advanced oesophageal squamous cell carcinoma who will benefit from preoperative CRT.

Adult↗

PubMed2002

Role of cytoplasmic calcium in platelet aggregation.

BACKGROUND: Although adherence and aggregation of platelets on an active surface such as exposed subendothelial matrix or foreign surfaces is integral to the occlusion of blood vessels, its mode of action is not fully understood. METHODS: The role of cytoplasmic ionized Ca(2+) concentration ([Ca(2+)](i)) in platelet activation induced by contact with a glass surface under shear-stress was studied by employing confocal laser scanning microscopy (CLSM) in conjunction with a parallel plate flow chamber. Changes in [Ca(2+)](i) and morphology of aggregating platelets on glass surface was simultaneously examined. RESULTS: Under static condition, contact with glass caused platelet adhesion to the surface, which was associated with [Ca(2+)](i) rise and morphological change; however, platelets did not develop a large aggregation on the surface. Under lower shear-stress, the number of the single platelets adsorbed on the surface was less than that under static condition. Although shear-stress increased the number of single platelets involved and enhanced morphological change in aggregating platelets in a shear-stress related manner, the peak [Ca(2+)](i) value in individual platelets were not increased. CONCLUSIONS: These observations may suggest the crucial roles of shear-stress in platelet aggregate formation at the site of arterial stenosis. Shear-stress might enhances platelet aggregate growth not through the enhancement of [Ca(2+)](i) rise.

Calcium↗

PubMed2002

An immunohistochemical study of cyclooxygenase (COX)-2 expression in endocrine tumors of the pancreas.

Cyclooxygenase (COX) is a key rate-limiting enzyme in prostaglandin biosynthesis. There are two isoforms of COX, referred to as COX-1 and COX-2. COX-2, an inducible form of COX, is found to be overexpressed in various neoplasms and is believed to play an important role in tumorigenesis and tumor development. In this study, we investigated expression of the COX-2 protein in human endocrine tumors of the pancreas (N=23; 6 insulinomas, one glucagnoma, 2 gastrinomas, and 14 non-functioning tumors) using immunohistochemistry. Strong COX-2 expression was confirmed in normal islet tissue as previously reported. COX-2 immunoreactivity was detected in 65% (15 out of 23) of these tumors with a moderate to strong intensity. In all nine functioning tumors, COX-2 expressions were preserved with the weak or strong intensity. In contrast, COX-2 was present in 6 out of 14 nonfunctioning tumors. The correlation between COX-2 expression and their function was significant (p<0.05). We found that expression of this enzyme was detected in 11 out of 15 benign tumors and in 4 out of 8 malignant tumors, respectively. Our results suggest that COX-2 may play an important role in the endocrine function of islet tumors. Additionally, malignancy was not related to COX-2 expression.

Adult↗

PubMed2001

Genetic detection of lymph node micrometastases in patients with gastric carcinoma by multiple-marker reverse transcriptase-polymerase chain reaction assay.

BACKGROUND: Some patients with gastric carcinoma experience local disease recurrence despite undergoing curative resection of the tumor and regional lymph nodes (LNs), suggesting the presence of occult micrometastases. To evaluate the presence of gastric carcinoma micrometastasis in patients with otherwise histologically negative LNs, the authors established and tested a multiple-marker reverse transcriptase-polymerase chain reaction (RT-PCR) assay. METHODS: The authors assessed 435 LNs from 28 patients with gastric carcinoma who underwent gastrectomy with lymphadenectomy using the multiple-marker RT-PCR assay in addition to histologic examination. Carcinoembryonic antigen (CEA), cytokeratin-20 (CK-20), and MAGE-3 gene markers were used in this assay. LNs were scored positive for metastasis if at least one marker was positive. The presence of LN micrometastases also was verified by immunohistochemistry in histologically negative and RT-PCR positive LNs. RESULTS: Sixty-nine of 435 LNs (16%) were positive for CEA (12%), CK-20 (10%), or MAGE-3 (5%). None of 16 control LNs obtained from disease free patients was positive by RT-PCR assay. Of 414 histologically negative LNs, 50 LNs (12%) were scored as positive for metastasis by the assay. Of 26 patients who underwent curative resection, the disease stage was upgraded in 10 patients by genetic diagnosis (from Stage IA to Stage IB in 5 patients, from Stage IB to Stage IIIA in 2 patients, from Stage IB to Stage IV in 1 patient, from Stage IB to Stage II in 1 patient, and from Stage II to Stage IIIB in 1 patient). In the latter 10 patients, immunohistochemistry identified LN micrometastases in 4 patients. Two patients with micrometastasis by genetic diagnosis had recurrent disease within 1 year. CONCLUSIONS: The current results indicate that the multiple-marker RT-PCR assay is a useful tool for the detection of micrometastases in regional LNs in patients with gastric carcinoma and may improve the staging system of gastric carcinoma for these patients.

Adult↗