Biomedical subjects

Ichiro Mori

Publications and source records attributed to Ichiro Mori.

At least 55 records · Page 3Linked to original sources

PubMed2002

Chromosome 3p and breast cancer.

Solid tumors in humans are now believed to develop through a multistep process that activates oncogenes and inactivates tumor suppressor genes. Loss of heterozygosity at chromosomes 3p25, 3p22-24, 3p21.3, 3p21.2-21.3, 3p14.2, 3p14.3, and 3p12 has been reported in breast cancers. Retinoid acid receptor beta2 (3p24), thyroid hormone receptor beta1 (3p24.3), Ras association domain family 1A (3p21.3), and the fragile histidine triad gene (3p14.2) have been considered as tumor suppressor genes (TSGs) for breast cancers. Epigenetic change may play an important role for the inactivation of these TSGs. Screens for promoter hypermethylation may be able to identify other TSGs in chromosome 3p. Alternatively, use of an "epigenetic modifier" may enhance the response to another type of agent for breast cancer.

Breast Neoplasms↗

PubMed2002

Abnormal iron deposition in renal cells in the rat with chronic angiotensin II administration.

Acute experimental iron loading causes iron to accumulate in the renal tissue. The accumulation of iron may play a role in enhancing oxidant-induced tubular injury by producing increased amounts of reactive oxygen species. From findings in cells from heme oxygenase-1 (HO-1)-deficient mice, HO-1 is postulated to prevent abnormal intracellular iron accumulation. Recently, it has been reported that HO-1 is induced in the renal tubular epithelial cells, in which iron is deposited after iron loading, and that this HO-1 induction may be involved in ameliorating iron-induced renal toxicity. We previously showed that chronic administration of angiotensin II to rats induces HO-1 expression in the tubular epithelial cells. These observations led us to investigate whether there is a link between iron deposition and HO-1 induction in renal tubular cells in rats undergoing angiotensin II infusion. In the present study, rats were given angiotensin II for continuously 7 days. Prussian blue staining revealed the distinct deposits of iron in the proximal tubular epithelial cells after angiotensin II administration. Electron microscopy demonstrated that iron particles were present in the lysosomes of these cells. Histologic and immunohistochemical analyses showed that stainable iron and immunoreactive ferritin and HO-1 were colocalized in the tubular epithelial cells. Treatment of angiotensin II-infused rats with an iron chelator, deferoxamine, blocked the abnormal iron deposition in kidneys and also the induced expression of HO-1 and ferritin expression. Furthermore, deferoxamine treatment suppressed the angiotensin II-induced increase in the urinary excretion of protein and N-acetyl-beta-D-glucosaminidase, a marker of tubular injury; however, deferoxamine did not affect the angiotensin II-induced decrease in glomerular filtration rate. These results suggest that angiotensin II causes renal injury, in part, by inducing the deposition of iron in the kidney.

Acetylglucosaminidase↗

PubMed2002

Heparanase: a key enzyme in invasion and metastasis of gastric carcinoma.

Previous reports have shown that the biochemical activity of heparanase is significantly correlated with the invasion and metastasis of malignant cells in vitro. Recently, it was found that the human heparanase gene was cloned and highly expressed in malignant cell lines and human solid malignant tumors. In the present study, we investigated the heparanase mRNA expression by using in situ hybridization in 116 paraffin-embedded tissues of primary gastric carcinomas. To explore its clinicopathologic significance, it was detected in the various steps of tumor progression and then compared with prognostic indicators. As a result, the heparanase expression was more prevalent in late-stage rather than early-stage carcinomas (P <.0001) and was more frequent in tumors of large size (P =.0212). Expression also correlated with lymphatic (P =.0086) and venous (P =.0171) invasion and with negative prognostic factors such as lymph nodal (P <.0001) and distant (P =.0221) metastases. However, in a multivariate analysis, messenger RNA expression of heparanase was not an independent prognostic factor. It was concluded that heparanase might play an important role in the development of invasion and metastasis of the gastric cancer. It was indicated that patients with heparanase-positive gastric carcinoma would have a greater chance of metastasis with a poor prognosis.

Female↗

PubMed2002

Predictive and prognostic markers for invasive breast cancer.

Breast cancer is one of the most serious carcinomas among women worldwide, yet there are now encouraging signs that improvements in the mortality rate may be possible. The use of hormone therapy and chemotherapy has been widely accepted as treatment for breast cancer. Predictive factors can be used to predict response or lack of response to a particular therapy, and prognostic factors can be useful in making decisions about which patients should receive adjuvant therapy. Histopathology remains the universal basis of diagnosis, with the identification of new surrogate markers for potential new treatments. These are aimed at blocking tumor cell proliferation, neutralizing growth factors, stimulating apoptosis and blocking metastasis, and represent an integral part of new approaches for improving clinical management of patients with breast cancer. We review the standard predictive and prognostic factors that are routinely available today, and also describe some of the new, potential markers that are currently under investigation.

Biomarkers, Tumor↗

PubMed2002

Helpful parameter for malignant potential of gastrointestinal stromal tumors (GIST).

BACKGROUND: Although a series of histopathological criteria have been suggested, the prediction of the malignant potential of gastrointestinal stromal tumors (GIST) is still difficult. The older literature called all gastrointestinal stromal tumors smooth muscle tumors or mixed GIST with true smooth muscle tumors. Reports on GIST including homogeneous cases were rare. METHODS: We examined 73 cases of GIST, which were immunohistochemically positive for c-kit and/or CD34, and mainly focused on the correlation between mitotic count and the other clinicopathological features to establish any helpful and reproducible parameters to indicate the malignant potential and to be used practically and objectively in the routine histopathological diagnosis of GIST. RESULTS: The results showed that there was a statistically significant difference in mitotic count between benign and malignant groups. Other proposed parameters, such as high cellularity, tumor size > or =5 cm, stomach and intestinal location, hemorrhage, necrosis, p53 expression and Ki-67 labeling index >10%, were frequently observed in tumors with mitotic figure. Three patients with one mitotic figure in 50HPF died from metastasis or recurrence of the tumors. CONCLUSIONS: Ki-67 index and cellularity should be used as predictors for the malignant potential of GIST. When other morphological features appear benign, mitotic count might also be a helpful practical factor in the prediction of the malignant potential of GIST.

Adolescent↗

PubMed2002

In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage.

The klotho gene, originally identified by insertional mutagenesis in mice, suppresses the expression of multiple aging-associated phenotypes. This gene is predominantly expressed in the kidney. Recent studies have shown that expression of renal klotho gene is regulated in animal models of metabolic diseases and in humans with chronic renal failure. However, little is known about the mechanisms and the physiological relevance of the regulation of the expression of the klotho gene in the kidney in some diseased conditions. In the present study, we first investigated the role of angiotensin II in the regulation of renal klotho gene expression. Long-term infusion of angiotensin II downregulated renal klotho gene expression at both the mRNA and protein levels. This angiotensin II-induced renal klotho downregulation was an angiotensin type 1 receptor-dependent but pressor-independent event. Adenovirus harboring mouse klotho gene (ad-klotho, 3.3x10(10) plaque forming units) was also intravenously administered immediately before starting angiotensin II infusion in some rats. This resulted in a robust induction of Klotho protein in the liver at day 4, which was still detectable 14 days after the gene transfer. Ad-klotho gene transfer, but not ad-lacZ gene transfer, caused an improvement of creatinine clearance, decrease in urinary protein excretion, and amelioration of histologically demonstrated tubulointerstitial damage induced by angiotensin II administration. Our data suggest that downregulation of the renal klotho gene may have an aggravative role in the development of renal damage induced by angiotensin II, and that induction of the klotho gene may have therapeutic possibilities in treating angiotensin II-induced end organ damage.

Angiotensin II↗

PubMed2002

Regulation and localization of HSP70 and HSP25 in the kidney of rats undergoing long-term administration of angiotensin II.

Various renal insults result in induction of heat shock protein (HSP) expression within the kidney. Some of the HSPs induced in that manner are postulated to have renoprotective effects via either chaperoning actions or antioxidative properties. We have previously reported that long-term angiotensin (Ang) II administration induces the expression of renal HSP32, also known as heme oxygenase-1 (HO-1). Here, we investigated the regulation of expression and localization of other HSPs, including HSP70, HSP25, and alphaB-crystallin, in the kidney of rats undergoing long-term administration of Ang II (0.7 mg. kg(-1). d(-1)). Immunoblot analysis demonstrated that Ang II increased renal expression of HSP70 and HSP25, as well as HO-1, but that expression of alphaB-crystallin was unaffected by this treatment. The Ang II-induced increase in renal HSP70 and HSP25 was dependent on the angiotensin type 1 receptor activation but not on hypertension per se. Immunohistochemistry revealed that HSP70 and HSP25 were expressed in the medullar regions and in the renal arterial wall in the kidney of control rats. After Ang II infusion, signals for HSP70, HSP25, and HO-1 proteins increased in intensity in the endothelium and medial smooth muscle of the renal artery. In addition, all of these HSPs were induced in proximal renal tubular epithelial cells from the same segments, suggesting that similar mechanisms are responsible for upregulating these HSPs. Our data show that Ang II infusion induces renal HSP70 and HSP25, as well as HO-1, and that Ang II can induce expression of these HSPs in renal cells in a pressor-independent manner.

Angiotensin II↗

PubMed2002

Parathyroid gland involvement by papillary carcinoma of the thyroid gland.

OBJECTIVE: To describe the phenomenon of parathyroid gland involvement by thyroid carcinoma and to explore its clinicopathologic significance. DESIGN: We reviewed the clinicopathologic features and described the histopathologic characteristics of 20 cases of parathyroid involvement found in a series of 911 papillary thyroid carcinomas. RESULTS: Parathyroid involvement occurred in 3 patterns: (1) direct invasion from the main tumor with an infiltrative growth, (2) invasion of the parathyroid gland with an expansive growth and formation of a pseudocapsule between the carcinoma and the parathyroid gland, and (3) metastatic deposition within the parathyroid gland itself. Among the 20 cases, 6 (30%) had primary tumors measuring 1 cm or less, and 14 (70%) had primary tumors measuring more than 1 cm. The cases with smaller primary tumors had a comparatively lower rate of nodal metastasis (50% vs 100%, P =.02). Furthermore, none of the cases with smaller primary tumors had invasion of extrathyroid structures other than parathyroid gland, but such invasion was common among the cases with larger primary tumors (0% vs 71%, P =.01). CONCLUSION: To the best of our knowledge, this is the first report showing that parathyroid involvement occurs in papillary thyroid carcinomas even in the early stage of the disease.

Adult↗

PubMed2002

Two-hit inactivation of FHIT by loss of heterozygosity and hypermethylation in breast cancer.

PURPOSE: The FHIT gene, which spans the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene in breast carcinomas. In this study, we would like to delineate more precisely its role in breast tumorigenesis. EXPERIMENTAL DESIGN: To confirm the tumorigenic role of FHIT, 46 sporadic invasive ductal carcinomas of the breast were tested for the "two hits" required to inactivate this gene. Microsatellite loss of heterozygosity (LOH) was considered as the first hit. To examine the possibility that hypermethylation serves as the second hit for FHIT inactivation, methylation of 5'-CpG islands of FHIT was analyzed by methylation-specific PCR. RESULTS: LOH was detected in 8 of 40 informative tumors, and hypermethylation was observed in 22 of 46 (48%) cases. Aberrant FHIT protein expression was found in 31 of 46 (67%) cases examined. All seven tumors showing both LOH and hypermethylation showed complete loss of Fhit protein expression. In addition, a significant positive association was found between the existence of LOH and 5'-CpG island hypermethylation (P = 0.04), which was consistent with the two-hit model. CONCLUSIONS: To our knowledge, this study provides the first evidence that biallelic inactivation of FHIT by LOH and hypermethylation leads to the complete inactivation of FHIT gene in patients with breast cancer. Silencing of the FHIT gene by promoter hypermethylation occurs in primary breast carcinomas, especially those with LOH. These findings support a role for this tumor suppressor gene in sporadic breast tumorigenesis.

Acid Anhydride Hydrolases↗

PubMed2002

Color image analysis of cervical neoplasia using RGB computer color specification.

OBJECTIVE: To establish quantitative color image analysis for cytology, red, green and blue (RGB) color specification was applied to Papanicolaou-stained cervical smears. STUDY DESIGN: Cell samples used in this study was those from 300 cervical specimens. We analyzed the color tone of nuclei and cytoplasm of the squamous cells in the cervical smear by means of computer image analysis. RESULTS: Papanicolaou stained nuclei displayed basophilic blue to purple. When they were hyperchromatic and deeply stained, B and G values decreased in value. The RGB values of cytoplasm and nuclei decreased significantly (P < .01) as their degree of cellular atypia increased. CONCLUSION: Using RGB color specification to analyze Papanicolaou-stained cervical smears, a significant difference was perceived in the nucleus and cytoplasm between different groups of squamous cells, from normal, dysplastic and squamous cell carcinoma. These findings may help to establish automated cytology.

Carcinoma in Situ↗

PubMedDate not supplied

Optimal covering material for stent-grafts placed in the portal vein in a canine model.

PURPOSE: We evaluated the suitability of Dacron, polytetrafluoroethylene (PTFE), and small intestinal submucosa (SIS) as a covering material for stent-grafts placed in the portal vein as compared with a bare stent. METHODS: Using 24 beagle dogs, either bare stents or stent-grafts covered with Dacron, PTFE, or SIS were placed in the main trunk of the portal vein in 6 animals each. Portography was performed immediately after stent placement, and at 2, 4, and 12 weeks thereafter. Next, the extracted stents or stent-grafts were examined histopathologically. Neointimal thickness adjacent to the stent wire and at the midportion between the stent wires was compared among the groups. Then, the neointimal thickness at the sub- and supragraft sites was compared between each stent-graft group. Serial changes in the histologic features of the thickened neointima were also investigated. RESULTS: No significant difference was noted in the mean stenotic ratio of the portal vein diameter between the bare stent and PTFE groups, whereas it was significantly higher in the Dacron and SIS groups compared with the bare stent group. In neither of the studies on neointimal thickness adjacent to the stent wire and at the midportion between the stent wires were any significant differences noted between the neointimal thickness of the bare stent group and the sum of the neointimal thickness of the PTFE group, whereas the sum of the neointimal thickness of the Dacron and SIS groups was significantly greater than that of the bare stent group at both sites. In the comparison of the supragraft neointimal thickness, the SIS group showed significantly greater thickness than the PTFE group, while the difference between the Dacron and PTFE groups was not significant. In the comparison of the subgraft neointimal thickness, the Dacron and SIS groups showed significantly greater thickness than the PTFE group. CONCLUSION: The present results indicate that of the three covering materials examined here, PTFE is the most suitable material for grafts placed in the portal vein.

Animals↗

PubMedDate not supplied

Loss of cell cohesion in breast cytology as a characteristic of neuroendocrine carcinoma.

OBJECTIVE: To characterize a specific group of breast cancers displaying a scattered single cell pattern in cytology and correlate it with histologic and immunohistochemical findings. STUDY DESIGN: Of 135 consecutive malignant breast cytologic specimens, 12 cases were selected for their scattered single cell pattern on aspiration cytology. Immunohistochemical staining for neuroendocrine markers and prognostic parameters was performed on paraffin sections of corresponding primary breast carcinomas. RESULTS: In the smears of the 12 cases, highly cellular neoplastic cells with a single cell pattern were observed predominantly. The tumor cells had relatively wide, granular cytoplasm and a low to moderate nuclear/cytoplasmic ratio. Histologically, they were arranged mainly in relatively large, solid nests and occasionally contained a tubular pattern with small amounts of stromal tissue. Five of the 12 cases demonstrated neuroendocrine differentiation with a positive immunoreaction for chromogranin A and synaptophysin. Except for the small mean size of the tumors (P < .01), no significant differences were identified among the prognostic parameters, including a nodal status, estrogen receptor status, growth fraction by Ki-67 or immunoreactivity for c-erbB-2, as compared with the other 123 cases. CONCLUSION: Loss of cell cohesion in breast cytology is a good morphologic marker for identifying neuroendocrine breast carcinoma.

Adult↗

PubMedDate not supplied

Correlation of prostate-specific antigen promoter polymorphisms with clinicopathological characteristics in breast cancer.

We have identified two novel polymorphisms in the prostate-specific antigen (PSA) gene promoter regions, the A-AA allele and G-A allele. Furthermore, we have found that A-AA occurred frequently in tumors with higher PSA expressions. We hypothesize that allelic differences may be associated with different phenotypes of breast cancer. To test this hypothesis, we assayed the PSA genotype for 101 breast cancer cases. We also performed immunostaining analysis for estrogen receptor, p53, MIB-1 and c-erbB-2 on all the tumors. At the time of diagnosis, the A-AA allele occurred more frequently in the tumors characterized by small tumor size, good to moderate differentiation, p53-negativity and low tumor proliferation activity. Our results suggest that the presence of the A-AA allele at the PSA promoter region is associated with less aggressive forms of breast cancer and could be looked on as a favorable prognostic factor.

Alleles↗

PubMedDate not supplied

Thymidine phosphorylase and breast carcinoma.

Thymidine phosphorylase (TP), also known as platelet-derived endothelial-cell growth factor (PD-ECGF), is an enzyme that catalyzes the reversible dephosphorylation of thymidine, deoxyguridine and their analogs. TP also has angiogenic properties, although the precise mechanism by which it promotes angiogenesis is not known. TP expression is elevated in many solid tumors including ductal carcinoma in situ and invasive carcinoma of the breast. This has led to intensive study to ascertain whether TP is a biological marker in breast carcinoma; however, the clinical work has produced conflicting results. Some studies have suggested that TP is angiogenic in breast carcinoma, however, we and others have found that TP has little effect on tumor angiogenesis of invasive breast carcinoma. However, increasingly clinical results suggest that TP could represent an interesting marker that could respond to pyrimidine analogues. Widespread application of TP in prognostic testing would require greater uniformity in scoring techniques and determination of the cut-off levels which could distinguish individuals at high and low risk of cancer recurrence and death.

Breast Neoplasms↗

PubMedDate not supplied

BRCA1 in non-inherited breast carcinomas (Review).

Breast cancer occurs in hereditary and sporadic form. Breast cancer susceptibility gene (BRCA1) is known to be responsible for hereditary breast cancer. BRCA1 mutations are rare in sporadic cancers, but loss of BRCA1 resulting from reduced expression or incorrect subcellular localization is postulated to be important in non-familial breast cancers. More than 300 germline mutations have been identified so far in patients with familial breast and/or ovarian cancer, however, only a few somatic mutations have been identified in sporadic breast cancer. The decreased expression of BRCA1 in sporadic breast cancer is thought to be caused by other mechanisms, such as CpG methylation. BRCA1 expression may play an important role in the pathogenesis and prognosis of sporadic breast carcinoma.

Aged↗

PubMedDate not supplied

Prognostic value of Bcl-2 in invasive breast cancer receiving chemotherapy and endocrine therapy.

Apoptosis induced by anticancer agents is a mechanism of treatment activity, overexpression of antiapoptotic genes could produce drug resistant tumors. We have demonstrated that the susceptibility of Bcl-2-negative tumors to a series of anticancer drugs was significantly higher than that of Bcl-2-positive tumors. The purpose of this study was to examine if negative Bcl-2 expression has treatment benefit in breast cancer patients received chemotherapy and endocrine treatment. A cohort of 147 Japanese women with invasive ductal carcinoma was studied. All the patients received postoperative adjuvant therapy consisting of combination chemotherapy with cyclophosphamide, epirubicin, and fluorouracil, and tamoxifen therapy. The expression of Bcl-2, estrogen receptor (ER) and MIB-1 was evaluated in breast cancer surgical specimens. Bcl-2 immunostaining was inversely correlated with increasing histologic grade (p=0.0095) and MIB-1 (p=0.0128). Furthermore, a positive correlation between Bcl-2 and ER was observed (p<0.0001). Unexpectedly, survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that Bcl-2-positivity was associated with favorable prognosis (p=0.0430). Cox proportional hazard model demonstrated that positive Bcl-2 expression still has favorable survival (p=0.0242) after consideration of other prognostic factors. Our results imply that Bcl-2 is a significant favorable prognostic factor for breast cancer with chemotherapy and endocrine therapy.

Adult↗

PubMedDate not supplied

Loss of Msh2 is not associated with FHIT deletion in breast carcinomas.

The FHIT gene is a candidate tumor suppressor gene that has been implicated in the development and progression of breast carcinoma. Recent studies have suggested that Fhit inactivation can be a consequence of defects in mismatch repair proteins, particularly Msh2. Fifty-three breast carcinomas were evaluated for Fhit and Msh2 expression by immunohistochemical staining. The same breast carcinomas were examined for allelic loss at three loci within or near FHIT by PCR-based microsatellite analysis. Seventeen of the 53 breast cancer cases were positive for Fhit protein, and 10 of the 43 informative cases showed FHIT loci deletion. Twenty-five of the 53 (47%) cases showed loss of Msh2 expression. No relationship between Msh2 protein loss and FHIT locus alteration or Fhit protein loss could be observed. Our results suggest that this mismatch repair protein may play little role in maintaining the integrity of the common fragile locus with the FHIT gene.

Acid Anhydride Hydrolases↗

PubMedDate not supplied

5-aza-2'-deoxycytidine induces retinoic acid receptor beta 2 demethylation, cell cycle arrest and growth inhibition in breast carcinoma cells.

Like all cancers, breast cancer is considered to result in part from the accumulation of multiple genetic alterations leading to oncogene overexpression and tumor suppressor loss. More recently, CpG island hypermethylation is known to be associated with gene silencing in cancer, and these silenced genes can be reactivated by 5-aza-2'-deoxycytidine (5-Aza-CdR). Retionoic acid receptor beta 2 gene is a tumor suppressor gene and the chemopreventive effects of retinoids are due to induction of RAR beta 2. In this study, the effect of 5-Aza-CdR RAR beta 2 restoration was investigated in the MRK-nu-1 human female breast cancer cell line. Changes of the RAR beta 2 methylation status were assessed by methylation-specific PCR. Reverse transcription PCR was used to evaluate RARb beta 2 restoration. Cell cycling and growth inhibition were studied using flow cytometric analysis of DNA content and CellTiter 96 AQueous non-radioactive cell proliferation assay, respectively. 5-Aza-CdR treatment resulted in complete demethylation of the RAR beta 2 gene. RAR beta 2 restoration was accompanied by cell cycle arrest (increase in the G0/G1- and decrease in the S- and G2/M-phases) and time-dependent growth inhibition. In conclusion, RAR beta 2 can be activated in vitro by 5-Aza-CdR, which may be one of the mechanisms for the tumor cell growth inhibition by 5-Aza-CdR.

Antimetabolites, Antineoplastic↗