Biomedical subjects

M Monden

Publications and source records attributed to M Monden.

At least 91 records · Page 5Linked to original sources

PubMed2000

Influence of CO2 pneumoperitoneum during laparoscopic surgery on cancer cell growth.

BACKGROUND: CO2 pneumoperitoneum provides a new surgical environment to treat malignant disease. The purpose of this study was to investigate the influence of CO2 pneumoperitoneum during laparoscopic surgery on cancer cell growth. METHODS: WiDr human colon cancer cells were incubated for 3 h under the following two conditions: 100% CO2 at 10 mmHg, and 95% air/5% CO2 (control). Cell proliferation was assessed by the WST-1 assay and BrdU assay. Tumor growth was assessed by subcutaneous injection into 20 nude mice. Cellular damage was measured by lactate dehydrogenase (LDH) assay. RESULTS: The number of WiDr cells under pneumoperitoneal conditions decreased in the first 24 h. However, no significant difference was observed in the proliferation rate and tumor growth of the viable cells. LDH release of the CO2 pneumoperitoneal group was higher than that of the controls. CONCLUSIONS: Our data indicate that CO2 pneumoperitoneum does not promote cancer cell proliferation but instead has a toxic effect on cancer cells.

Carbon Dioxide↗

PubMed2000

Squamous cell carcinoma of the esophagus infiltrating the respiratory tract is less sensitive to preoperative concurrent radiation and chemotherapy.

BACKGROUND: The prognosis of upper thoracic esophageal cancer is poor when compared with middle and lower thoracic esophageal cancer because the tumor easily infiltrates the respiratory tract and surgical en-bloc resection is difficult. Recently, preoperative chemoradiation therapy has been shown to lead to down-staging of the disease and improve prognosis. But the benefit of this therapy for tumors infiltrating the respiratory tract remains unknown. STUDY DESIGN: Fifty-six patients with thoracic esophageal cancer infiltrating neighboring organs, but with no hematogeneous metastasis, were given preoperative concurrent chemotherapy (5-fluorouracil and cisplatin) and radiation (40 Gy) therapy. When a clinical response was observed, making a curative resection potentially possible, patients were scheduled for esophagectomy with extended lymphadenectomy. Patient prognosis with respect to the organs infiltrated by the tumors was estimated by calculating survival curves using the Kaplan-Meier method and comparing the curves by the log-rank test. RESULTS: The prognosis was significantly poorer for patients with tumors infiltrating the respiratory tract (T) or aorta plus respiratory tract (A + T) than for patients with tumors infiltrating the aorta alone (A) or other organs (Oth) (p < 0.05 for Oth versus T; p < 0.05 for Oth versus A + T; p < 0.0001 for A versus T; p < 0.0001 for A versus A + T by log-rank test). Patients positive for respiratory tract invasion (T, T + A), compared with those negative for respiratory tract invasion (A, Oth), showed a poorer clinical response to chemoradiation (3.0%, 45.5%, 39.4%, and 9.1% versus 4.3%, 82.6%, 4.3%, and 8.7% in complete response (CR), partial response (PR), nonresponse (NC) and progressive disease (PD), respectively, p = 0.0156) and surgical resectability (36.4% vs. 87.0%, p = 0.0003). Histologic effectiveness (8.3%, 50.0%, and 41.7% versus 25.0%, 70.0%, and 5.0% in grade 3, grade 2, and grade 1, respectively, for patients with respiratory tract invasion versus those without it, p = 0.0189) and histologic stages (8.3%, 8.3%, 8.3%, 8.3%, 25.0%, and 41.7% versus 20.0%, 0%, 15.0%, 25.0%, 40.0%, and 0% in pathologic CR, stage I, stage IIA, stage IIB, stage III, and stage IV, respectively, for patients with respiratory tract invasion versus those without it, p = 0.0496) were significantly better in patients negative for respiratory tract invasion; the percentages of patients with lymph node metastasis did not differ significantly between the two groups. Comparison of the recurrence patterns showed that local failure was most common in patients with respiratory tract invasion, and distant failure was the leading cause of recurrence in patients without it. CONCLUSIONS: Because the prognosis of patients with thoracic esophageal cancer infiltrating the respiratory tract is extremely poor, partially because of the low local effectiveness of preoperative concurrent chemotherapy and radiation therapy, caution is needed when deciding on salvage surgery.

Adult↗

PubMed2000

Development of a multiple-marker RT-PCR assay for detection of micrometastases of hepatocellular carcinoma.

We investigated the expression of several candidate gene markers: MAGE-1, MAGE-3, cytokeratin-20 (CK-20), and alpha-fetoprotein (AFP) in tumor tissue and blood specimens from patients with hepatocellular carcinoma to develop a multiple marker reverse transcriptase-polymerase chain reaction (RT-PCR) assay for detection of micrometastasis in circulation. In 24 tumor specimens, the positivity for MAGE-1, MAGE-3, AFP, and CK-20 genes was 71, 67, 88, and 79% respectively, and all specimens expressed at least one marker. Although AFP and CK-20 transcripts were also detected in corresponding noncancerous liver specimens, none of the 22 corresponding normal specimens or seven normal livers were positive for MAGE-1 or MAGE-3 transcripts. In addition, MAGE-1 and MAGE-3 gene transcripts were not detected in any peripheral blood specimens from 31 normal healthy volunteers. MAGE-1, MAGE-3, and AFP transcripts were detected in 9 (12.7%), 3 (4.8%), and 10 (15.9%) of 71 blood specimens from 11 hepatocellular carcinoma patients, respectively, while 19 specimens (26.8%) were positive for at least one marker. Our results indicate that a multimarker RT-PCR assay with cancer-specific markers such as MAGE-1 and MAGE-3 in combination with a liver-specific AFP marker may be a promising diagnostic tool for monitoring hepatocellular carcinoma patients with better sensitivity and specificity.

Blood Physiological Phenomena↗

PubMed2000

Presence of active hepatitis associated with liver cirrhosis is a risk factor for mortality caused by posthepatectomy liver failure.

The histologic activity of associated hepatitis was examined in 285 patients who underwent hepatectomy for hepatocellular carcinoma (HCC), to determine if the histologic activity is an independent risk factor for postoperative mortality due to liver failure. The proportion of patients with liver cirrhosis who died due to liver failure (6/180, 3.3%) was not different from that of patients with chronic hepatitis (2/68, 2.9%). However, mortality was higher in patients with liver cirrhosis and active hepatitis (4/46, 8.7%) than in those with cirrhosis and inactive hepatitis (2/134, 1.5%, P < 0.05). Such difference was not observed in the chronic hepatitis group. Multivariate analysis showed that clearance of indocyanine green at 15 min (ICGR15) and activity of hepatitis were two independent risk factors for postoperative mortality due to liver failure. In conclusion, histologic activity of associated hepatitis should be taken into account in hepatic resection of HCC in cirrhotic liver, in addition to the functional reserve of the liver.

Adult↗

PubMed2000

Detection of microsatellite alterations in nipple discharge accompanied by breast cancer.

Nipple discharge in breast cancer cases was examined loss of heterozygosity (LOH). DNA samples were extracted from both supernatant and cell pellet components of the discharge, and examined for LOH at microsatellite markers, D11S1818, D11S2000, D16S402, D16S504, D16S518, D17S520, and D17S786. At least one LOH was found in either the supernatant or cell pellet in seven out of 10 patients (70%). Five of seven samples, which were cytologically negative, were LOH positive, and only one case, which was cytologically positive, showed no LOH on the markers examined. All three samples, which were judged 'negative' by CEA measurement (<400 ng/ml), were LOH positive. This method could be a useful novel diagnostic modality for nonpalpable breast cancer with nipple discharge.

Adult↗

PubMed2000

Distinct transcriptional regulation and phylogenetic divergence of human LEFTY genes.

BACKGROUND: Mouse lefty1 and lefty2 genes are expressed on the left side of developing embryos and are required for left-right determination. Here we have studied expression and transcriptional regulatory mechanisms of human LEFTY genes. RESULTS: The human LEFTY locus comprises two functional genes (LEFTY1 and LEFTY2) and a putative pseudogene. LEFTY1 is expressed in colon crypts. However, whereas LEFTY1 mRNA is present in basal cells of the crypts, LEFTY1 protein is localized in the apical region, suggesting that this secreted protein undergoes long-range transport. Human LEFTY2 possesses a left side-specific enhancer (ASE) like mouse lefty2; however, the LEFTY2 ASE shows markedly higher activity in the floor plate than does the lefty2 ASE. In contrast to mouse lefty1, which is expressed predominantly in the floor plate under the control of a right side-specific silencer, human LEFTY1 is expressed mainly in left lateral plate mesoderm under the control of an ASE-like left side-specific enhancer. The presence of FAST-binding sites in the LEFTY1 enhancer (and their absence in lefty1) contributes to the difference. CONCLUSION: These observations suggest that humans and mice have acquired distinct strategies during evolution for determining the asymmetric expression of LEFTY and lefty genes.

Amino Acid Sequence↗

PubMed2000

Ankycorbin: a novel actin cytoskeleton-associated protein.

BACKGROUND: Actin cytoskeleton structures are essential for a wide variety of cell functions, including cell shape change, cell motility, cell adhesion, cell polarity and cytokinesis. Many actin filament (F-actin)-binding proteins have been isolated and implicated in the maintenance and reorganization of actin cytoskeleton structures. RESULTS: We purified here a novel protein with a molecular mass of about 125 kDa (p125) from rat liver. We cloned its cDNA from a mouse kidney cDNA library and determined its nucleotide and deduced amino acid sequences. p125 was a protein of 979 amino acids with a calculated Mr of 108 847. p125 contained six ankyrin repeats in the N-terminal region and a domain predicted to form a coiled-coil structure in the C-terminal region. We named p125 ankycorbin (ankyrin repeat- and coiled-coil structure-containing protein). Northern blot analysis indicated that ankycorbin was ubiquitously expressed in all the tissues examined. Immunofluorescence and immunoelectron microscope analyses revealed that ankycorbin was associated with the cortical actin cytoskeleton structures in terminal web and cell-cell adhesion sites and stress fibres. However, ankycorbin did not directly bind to F-actin as estimated by the F-actin co-sedimentation assay. CONCLUSIONS: These results indicate that ankycorbin is indirectly associated with the actin cytoskeleton structures, presumably through an unidentified factor and suggest that it is involved in their maintenance and/or reorganization.

3T3 Cells↗

PubMed2000

Advanced hepatocellular carcinoma with distant metastases, successfully treated by a combination therapy of alpha-interferon and oral tegafur/uracil.

We report a case of advanced hepatocellular carcinoma (HCC), successfully treated by a combination therapy of alpha-interferon (IFN-alpha) and tegafur/uracil (UFT). A 44-year-old Japanese man who underwent a partial hepatectomy for HCC developed tumor recurrence in the liver 10 months after surgery. Transcatheter arterial chemoembolization (TAE) was performed twice within 7 months, but was ineffective. Later, multiple metastatic lesions appeared in the liver, lung and spine. Following the third TAE, a combination therapy of IFN-alpha (10 x 10(6) units, i.m., t.i.w.) and UFT (300 mg, p.o.d.) was started. The treatment resulted in a fall in serum PIVKA-II (protein induced by vitamin K antagonism) levels from 906 mAU to normal levels and a complete resolution of all lung nodules within 6 months. At the latest follow up 24 months after the initiation of combination treatment, the patient was working full-time and showed no evidence of tumor relapse. A combination therapy of IFN-alpha and UFT may be promising for the treatment of advanced HCC.

Administration, Oral↗

PubMed2000

Larynx preservation in surgical treatment of cervical esophageal cancer--combined procedure of laryngeal suspension and cricopharyngeal myotomy.

From July 1994 to July 1998, a larynx-preserving procedure was performed on 10 out of 22 (45%) patients in the surgical treatment of hypopharyngeal and cervical esophageal cancer. At first, all 10 patients were treated with concurrent radiochemotherapy with cisplatin (10 mg/m2/day), 5-fluorouracil (500 mg/m2/day) and radiation (2 Gy/day) five times per week for 4 weeks. After preoperative radiochemotherapy, the larynx-preserving procedure, combining laryngeal suspension and cricopharyngeal myotomy, was performed. The operative and hospital mortality rate was 0%. The incidence of post-operative morbidity with minor complications was 70% in the present study. Laryngeal speech and oral food intake were preserved in all patients after this procedure. The new larynx-preserving procedure combining laryngeal suspension and cricopharyngeal myotomy for cervical esophageal cancer is a favorable operative method for retaining intelligible laryngeal speech and good food intake.

Adult↗

PubMed2000

Evaluation of the histologic effect of chemoradiation therapy for squamous cell carcinomas of the esophagus by assessing morphologic features of surgical specimens.

The histologic effects of chemoradiation therapy (CRT) for esophageal cancer, which determine the benefit obtained from a salvage operation, are difficult to evaluate preoperatively. We therefore investigated whether or not the morphologic features of esophageal cancer tissue after CRT can be correlated with the histologic features of the tissue. Seventy-six patients with advanced esophageal squamous cell carcinoma underwent CRT followed by esophagectomy. The effects of CRT were evaluated by histologic examination of the residual tumors in the surgical specimen and correlated with clinicopathologic factors, including postoperative prognosis. The histologic effects of CRT were used to classify tumors as grade 1 (CRT poorly effective; 23 cases, 30.3%); grade 2 (CRT moderately effective; 31 cases, 40.8%); or grade 3 (CRT completely effective with no residual tumors; 22 cases, 28.9%). Among the gross findings of the removed esophagus, significant correlation with the CRT effects was observed in the case of wall thickness and ulceration but not in the case of longitudinal tumor length. Tumors with no wall thickening or ulceration were never classified as grade 1, whereas tumors with both wall thickening and ulceration were frequently rated as grade 1 (18/30, 60%). Microscopic examination of grade 2 tumors (23/31, 74.1%) revealed residual tumor cells growing below the mucosal layer, whereas tumor cells were exposed to the esophageal surface in 22 out of 23 patients with grade 1 tumors. The morphologic features after CRT can be used to evaluate its histologic effect, especially in the case of grade 1 tumors. However, the detection and prediction of grade 2 tumors remains difficult because of the presence of small amounts of residual tumor underneath the mucosa.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Superparamagnetic iron oxide-enhanced magnetic resonance images of hepatocellular carcinoma: correlation with histological grading.

Superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging has been used for the detection of hepatic tumors. However, little is known about this technique in relation to hepatocellular carcinoma (HCC). The aim of this study was to investigate whether SPIO-enhanced MR imaging can be useful in assessing histological grades of HCC. The authors studied histologically proven tumors including 31 HCCs and 6 dysplastic nodules. The ratio of the Kupffer-cell count in the tumorous tissue relative to that in the nontumorous tissue (Kupffer-cell-count ratio) decreased as HCCs became less well differentiated. The ratio of the intensity of the tumorous lesion to that of the nontumorous area on SPIO-enhanced MR images (SPIO intensity ratio) correlated inversely with Kupffer-cell-count ratio in HCCs and dysplastic nodules (r = -.826, P <.001) and increased as the degree of differentiation of HCCs decreased, indicating that the uptake of SPIO in HCCs decreased as the degree of differentiation of HCCs declined. All of the dysplastic nodules and some well-differentiated HCCs showed hypointense or isointense enhancement, relative to the surrounding liver parenchyma, indicating greater or similar uptake of SPIO in the tumor when compared with nontumorous areas. These results suggest that SPIO-enhanced MR imaging reflects Kupffer-cell numbers in HCCs and dysplastic nodules, and is useful for estimation of histological grading in HCCs, although uncertainties persist in differentiating dysplastic nodules from well-differentiated HCCs.

Aged↗

PubMed2000

The status of Fas and Fas ligand expression can predict recurrence of hepatocellular carcinoma.

The status of Fas and Fas ligand (Fas L) expression was investigated in this study for 103 hepatocellular carcinomas (HCC). We studied the expression of the following three factors, Fas and Fas L expression in carcinoma cells and Fas L expression in stromal mononuclear cells (defined as stromal Fas L index). Fas expression in HCC cells was significantly decreased in cases with poor differentiation (P < 0.0001) and of larger size (P = 0.0058). Fas L expression in carcinoma cells was observed exclusively in moderately or poorly differentiated cases. Furthermore, each factor had prognostic significance for disease-free survival (DFS) (P< 0.0001, P = 0.0222 and 0.0027 respectively). We then scored the results of each factor and defined the total score as 'Fas-Fas L risk score'. The P-value of the score for DFS was even lower than that of the clinical stage by multivariate analysis. These results suggest that the evaluation of Fas and Fas ligand expression potentially has a significant prognostic value for DFS of HCC patients, in addition to the clinical stage, and can be regarded as a new prognostic marker.

Aged↗

PubMed2000

Clinical application of malignancy potential grading as a prognostic factor of human esophageal cancers.

BACKGROUND: Various biologic markers have been reported to be prognostic factors in human esophageal cancers. In the current study, we established a new tumor-grading system representing the malignancy potential of cancer cells and compared it with the clinical-stage system. METHODS: Tumor samples from 77 patients with squamous cell carcinoma of the esophagus were immunohistochemically evaluated for the expression of 10 molecules: the cell cycle-related molecules of cyclin D1, Rb, p16INK4, p27KIP1, and PCNA; the cell-cell adhesion molecules of E-cadherin, alpha-catenin, and beta-catenin; and the heat shock proteins of HSP27 and HSP70. RESULTS: P27KIP1, beta-catenin, and HSP70 were selected for their high hazard ratio in multivariate analysis, and the number of their disordered molecules was used to define the malignancy grade (MG). Five-year survival rates were 83%, 54%, 17%, and 0% for MG1, MG2, MG3, and MG4. The gradation of survival curves was better for MGs than for clinical stages. MGs and clinical stages showed significant correlation; however, 55% of those in higher clinical stages (stage 3 or 4) had lower MG (MG1 or 2) and showed better prognosis than others in their group (stage 3 or 4 and MG3 or 4). The proportions of shorter survival span to cancer death patients (less than 1 year) were 0%, 33%, 75%, and 100% in MG1, 2, 3, and 4, but the clinical stage was not associated with the survival span. CONCLUSIONS: The grading of malignancy potential is clinically useful, especially for selecting patients who may show good prognosis in the advanced clinical stage and for predicting short survival span. These predictions are not possible with the clinical-stage system, which is based on the anatomic spread of cancer cells.

Cell Cycle Proteins↗

PubMed2000

PTEN / MMAC1 mutation and frequent loss of heterozygosity identified in chromosome 10q in a subset of hepatocellular carcinomas.

Frequent allelic losses on chromosome 10q have been reported in several types of cancers, suggesting the presence of a putative tumor suppressor gene(s) on the chromosomal arm. We examined loss of heterozygosity (LOH) on chromosome 10q in 37 hepatocellular carcinomas (HCC) using eleven dinucleotide microsatellite markers, spanning the entire chromosome arm of 10q. Twelve (32%) out of 37 informative cases showed allelic losses of at least one locus on 10q and eight tumors showed a partial deletion of 10q. Analysis of deletion mapping of these eight cases identified two commonly deleted regions within the distal part of 10q (10q24-q26), a 20-cM interval flanked by D10S597 and D10S216 and a 24-cM interval flanked by D10S216 and D10S590. Moreover, we detected a somatic missense mutation (Met --> Val) of a candidate tumor suppressor gene PTEN / MMAC1, located at 10q23.3, in one HCC with LOH of 10q. Our findings indicated the presence of putative tumor suppressor gene(s) in the distal region of 10q that might be involved in the development and progression of HCC. Inactivation of PTEN / MMAC1 gene located outside the commonly deleted region of 10q might also play an important role in a subset of HCCs.

Carcinoma, Hepatocellular↗

PubMed2000

Expression of tumor suppressor gene p16(INK4) products in primary gastric cancer.

Recent studies have shown that the cyclin-dependent kinase (CDK) inhibitor p27(Kip1) represents an indicator for patients' outcome in several human malignancies including gastric cancer. However, the clinicopathologic value of another class of CDK inhibitor, p16(INK4), has not been determined. In a retrospective study, we examined the expression of p16(INK4) by immunohistochemical assay of 80 samples of primary gastric cancers and their adjacent nonneoplastic mucosas. Less than 10% of non-tumor gastric mucosal cells were p16(INK4) positive, whereas the expression of p16(INK4) in gastric cancer cells varied widely from 0 to 100% (mean, 24.5%). The expression of p16(INK4) was not seen in 11.3% (9/80) of the cancer cases, but in 65% (52/80) this protein was even overexpressed when compared with the nonneoplastic mucosa. A clinicopathologic survey indicated that a low or no expression of p16(INK4) was associated with poorly differentiated carcinoma (p = 0.0133), but the level of expression did not correlate with other parameters including patients' prognosis or with the expression of the pRb protein. In an effort to explore the underlying mechanism for the p16(INK4)-negative cases, a prospective study was also performed on 20 cases of gastric cancer to compare the level of the p16(INK4) protein with the methylation status of the p16(INK4) promoter. Gastric cancer tissues with methylation expressed significantly lower levels of the p16(INK4) protein (p = 0.0013) and two of them lacked p16(INK4) expression altogether, whereas all the cancer tissues without methylation expressed it. These findings suggest that the p16(INK4) protein may be associated with differentiation of gastric cancer tissues and that methylation of the p16(INK4) promoter may, in part, account for the loss of p16(INK4) expression.

Blotting, Western↗

PubMed2000

Loss of p27(KIP1) expression predicts poor prognosis in patients with esophageal squamous cell carcinoma.

Immunohistochemical studies of cell cycle-regulating proteins were conducted on tissue samples from 106 patients with esophageal squamous cell carcinoma. Reduction of p27(KIP1) was observed in 41 (39%) cases and was significantly associated with a poor prognosis by univariate and multivariate analyses (p = 0.015). In contrast, p16(INK4) expression was reduced in 55 (52%) of the cases and was not correlated with prognosis. p27(KIP1) was not correlated with the PCNA index, while p16(INK4) expression was inversely correlated with the PCNA index (p = 0.01). The expression of these two proteins was not correlated with the clinicopathological parameters of the patients. Nodal status was shown by univariate analysis (p = 0.01) to be a prognostic factor, and poorly differentiated tumors were significantly associated with a poor prognosis by multivariate analysis (p = 0.027). Thus, reduction of p27(KIP1) plays an important role in the progression of esophageal squamous cell carcinomas and is considered to be an independent prognostic indicator of this disease.

Adult↗

PubMed2000

ets-1 expression in extrahepatic bile duct carcinoma and cholangiocellular carcinoma.

ets-1 is a transcription factor known to induce the expression of various genes important for carcinoma progression. However, its clinical significance does not seem to be uniform for all carcinomas. In this study, we investigated the ets-1 expression in 41 extrahepatic bile duct carcinomas (BDC) and 19 cholangiocellular carcinomas (CCC). Epithelial cells of normal ducts only occasionally expressed ets-1, whereas cells of reactive ducts and dysplastic ducts were often positive for this protein. On the other hand, 61.0% of BDC and 21.6% of CCC were classified as ets-1-positive, because more than 5% of the carcinoma cells expressed ets-1. The expression of ets-1 showed inverse relationships with the Ki-67-labeling index and vascular and perineural invasion of BDC, whereas no such relationships could be established in CCC. Furthermore, the well-differentiated BCD more frequently expressed ets-1. These results suggest that ets-1 works as a transcription factor in malignant transformation and progression in early phases of BDC.

Aged↗

PubMed2000

Bcl-2 expression in cholangiocellular carcinoma is inversely correlated with biologically aggressive phenotypes.

bcl-2 is known to play a crucial role in modulating carcinoma progression as well as in inhibiting apoptosis. However, its expression and clinical significance for cholangiocellular carcinoma (CCC) remains unclear. In the present study, we immunohistochemically investigated bcl-2 expression in 41 CCC. Thirteen cases (31.7%) were classified as bcl-2 positive, because more than 10% of the carcinoma cells expressed bcl-2. The expression of bcl-2 was inversely related to lymph node metastasis, vascular invasion, perineural invasion, the Ki-67 labeling index, aberrant p53 expression and the incidence of apoptotic cells. Furthermore, well or moderately differentiated carcinoma more frequently expressed bcl-2. These results suggest that downregulation of bcl-2 expression is strongly linked to highly biologically aggressive phenotypes of CCC.

Bile Duct Neoplasms↗