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Biomedical subjects

M Toi

Publications and source records attributed to M Toi.

At least 55 records · Page 3Linked to original sources
PubMed2002

High molecular weight caldesmon positive stromal cells in the capsule of thyroid follicular tumours and tumour-like lesions.

AIMS: To investigate the smooth muscle nature of the spindle stromal cells in the capsule of thyroid tumours and tumour-like lesions. METHODS: Immunostaining for high molecular weight caldesmon (HCD), a highly specific marker for smooth muscle differentiation, was performed in 70 primary thyroid tumours and tumour-like lesions (21 hyperplastic nodules, 29 follicular adenomas, five minimally invasive follicular carcinomas, six widely invasive follicular carcinomas, and nine encapsulated papillary carcinomas). RESULTS: HCD positive stromal cells (HCD+ cells) were detected in the capsule of 20 of the 21 hyperplastic nodules, and all of the 29 follicular adenomas and five minimally invasive follicular carcinomas, whereas HCD+ cells were seen in the capsule of only four of the six widely invasive follicular carcinomas and no HCD+ cells were seen in the capsule of the nine encapsulated papillary carcinomas examined. CONCLUSIONS: The presence of HCD+ cells in the capsule is characteristic of thyroid follicular tumours and tumour-like lesions. The stromal cells in the capsule of thyroid follicular tumours and tumour-like lesions are different from those of encapsulated papillary carcinoma.

Adenocarcinoma, Follicular↗
PubMed2002

Lack of CD34 positive stromal cells within angiomyomas (vascular leiomyomas).

AIMS: To investigate the role of CD34 positive stromal cells in the morphogenesis and tumour growth regulation of angiomyomas (vascular leiomyomas). METHODS: Histochemical analysis using monoclonal antibodies to CD34 and CD31 was performed in 10 angiomyomas and their adjacent soft tissue. RESULTS: CD34 positive stromal cells were not seen within the tumour tissue; the thick walled vessels within the tumours lacked CD34 positive stromal cells. In contrast, bundles of CD34 positive stromal cells were detected at the tumour border of all of the angiomyomas and in the adventitial tissue of the surrounding normal vessels. CONCLUSIONS: The lack of CD34 positive stromal cells within an angiomyoma is associated with the characteristic morphology of an angiomyoma.

Angiomyoma↗
PubMed2002

Review of collecting duct carcinoma with focus on clinical and pathobiological aspects.

In recent years, the concept of collecting duct carcinoma (CDC) has been established. CDCs constitute about 0.4 to 2% of RCCs. Macroscopically, CDCs occur in the renal medulla. On the cut surface, they are generally firm, white or grey and poorly circumscribed. Histologically, CDCs are characterized by various cytological and histological appearances. Furthermore, desmoplastic stromal reaction around the tumor and atypical hyperplastic changes or carcinoma in situ in the adjacent medullary collecting duct are frequently observed. Histological distinction from papillary RCCs is most important, because both tumors share some structural and histochemical features, and it seems that some investigators have confused diagnostic criteria for CDCs. On the other hand, the concept of medullary carcinoma, which preferentially occurs in a black race and shows histological features similar to those of CDC, has also recently been established. Although there have been few studies on chromosomal abnormalities of CDCs and consistent abnormalities have not been identified, a recent study using microsatellite analysis has shown a high frequency (60%) of LOH in 1q32.1-32.2. Further studies are needed to elucidate the genetic characteristics of CDCs and to determine the relationship or difference between CDCs and medullary carcinomas.

Animals↗
PubMed2001

Different features of angiogenesis between ovarian and breast carcinoma.

Angiogenesis assessed by immunohistochemical staining for endothelial cells has been widely accepted as an independent prognostic factor in human breast carcinoma. However, the clinicopathologic significance of angiogenesis is still being argued in ovarian carcinoma. Therefore, we retrospectively analyzed the clinicopathologic significance of angiogenesis in ovarian carcinoma compared with that in breast carcinoma. After vessels were stained with CD34-monoclonal antibody, the areas with the highest number of intratumoral microvessels were assessed in a 200x field in 42 ovarian carcinoma and 41 breast carcinoma. Intratumoral microvessel density (IMD) in ovarian carcinoma was significantly lower than that in breast carcinoma. Further, the difference of IMD from tumor to tumor in ovarian carcinoma was smaller than that in breast carcinoma. IMD was correlated with tumor grade, but not with other clinicopathologic variables in ovarian carcinoma. Although the patients with high-IMD tumor revealed a poorer prognosis than those with low-IMD tumor in breast carcinoma, IMD had no influential effects on the survival of the patients with ovarian carcinoma. Our comparative analysis of IMD in ovarian carcinoma with that in breast carcinoma indicates that angiogenesis may play an important role in the transient of ovarian neoplasms, but not in the progression of ovarian carcinomas, and that the biological roles of angiogenesis might be different, depending on histologic subtype.

Adult↗
PubMed2001

Significant correlation of monocyte chemoattractant protein-1 expression with neovascularization and progression of breast carcinoma.

BACKGROUND: Macrophages often infiltrate into solid tumor tissues. Tumor-associated macrophages (TAMs) are known to play a crucial role in tumor progression. Monocyte chemoattractant protein-1 (MCP-1) is one of the major chemokines capable of inducing chemotactic migration of monocytes. METHODS: With the objective of investigating the clinical significance of MCP-1, the authors analyzed the expression of MCP-1 and of some other molecules by immunohistochemistry in 230 samples of primary breast carcinoma tissue. MCP-1 staining was performed using an anti-MCP-1 monoclonal antibody, and it was assessed by grading the percentage of stained cells. RESULTS: It was found that 117 breast tumor specimens (51%) had intensive staining in tumor cells. The expression of MCP-1 in tumor cells had a significant correlation with the expression of thymidine phosphorylase and membrane type 1-matrix metalloproteinase. In addition, MCP-1 expression tended to be associated with the accumulation of TAMs, which were counted by CD68 staining, and with microvessel density. MCP-1 expression in TAMs was correlated significantly with the histologic vessel invasion of tumor cells. CONCLUSIONS: The results of this study suggest that MCP-1 may play key roles in macrophage recruitment, in the expression of angiogenic factors, and in the activation of matrix metalloproteinases in patients with breast carcinoma.

Angiogenesis Inducing Agents↗
PubMed2001

MDM2 enhances the function of estrogen receptor alpha in human breast cancer cells.

Overexpression of the oncoprotein MDM2, a negative feedback regulator of p53, is often observed in breast cancer tissue and cell lines, particularly in those which express estrogen receptor alpha (ERalpha). In this study, we report a novel function of MDM2, i.e., as a positive regulator of ERalpha. This function does not involve p53. MDM2 overexpressing clones derived from the breast cancer cell line, MCF-7 cells, showed a remarkable growth advantage only in estradiol supplemented conditions, and this profile coincided with increased transcriptional activity of ERalpha in these cells. Though p53 has been reported to be an inhibitor of ERalpha function, p53 protein in MDM2 overexpressing clones was more abundant than in the parental cells. When ERalpha was exogenously expressed in p53-null cells, its activity was enhanced by coexpression of MDM2. Mammalian two-hybrid assays and GST pull-down assays indicated that MDM2 could interact with ERalpha. These results indicate that MDM2 is a direct activator of ERalpha function, and suggest such a role for MDM2 in ERalpha-positive breast cancer.

Blotting, Western↗
PubMed2001

Evaluation of HER2 status: for the treatment of metastatic breast cancers by humanized anti-HER2 Monoclonal antibody (trastuzumab) (Pathological committee for optimal use of trastuzumab).

For the treatment of patients with metastatic breast cancer by humanized anti- human epidermal growth factor receptor type 2 (HER2) antibody (trastuzumab), it is important to evaluate HER2 status adequately. "A guideline for HER2 testing" and "HER2 atlas" produced by the "Pathological committee for optimal use of trastuzumab" are introduced in this report. Appropriate evaluations of biological markers are essential for targeting therapy.

Antibodies, Monoclonal↗
PubMed2001

Aromatase and aromatase inhibitors.

Aromatase inhibition provides both paracrine/intracrine and endocrine treatment. Recent accumulated data clarified that 3rd generation aromatase inhibitors potently suppress intratumoral estrogen synthesis particularly in postmenopausal patients. In the 2nd-line treatment for metastatic breast cancer patients, aromatase inhibitors achieved results antitumor activity at least equal to and sometimes better than that of tamoxifen. In the first-line treatment for metastatic breast cancer patients, a recent pivotal study clearly demonstrated that aromatase inhibitor was superior to tamoxifen. Based upon these results, various adjuvant trials which compare aromatase inhibitors with tamoxifen and attempt to determine optimal combination therapies and treatment periods with aromatase inhibitors are currently being conducted. In addition, preliminary studies conducted in neoadjuvant setting indicated that aromatase inhibitors showed an extremely high response rate, which predicts a future paradigm, that neoadjuvant therapy using aromatase inhibitors singly or in combination may become standard for hormone-responsive and post-menopausal breast cancer patients.

Anastrozole↗
PubMed2001

Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications.

Since the discovery that cancer development requires the growth of new blood vessels, many investigations have revealed the key molecules in the regulation of new vessel formation. One of the most important of these molecules is vascular endothelial growth factor (VEGF)--an endothelial-cell-specific mitogen and survival factor. VEGF also causes increased vascular permeability and recruits progenitor endothelial cells from the bone marrow. Clinical observations have confirmed that VEGF status is closely associated with the extent of neovascularisation and prognosis in many solid tumours. VEGF status is predictive of resistance to various treatments, including radiotherapy, chemotherapy, and endocrine therapy. Preliminary results also indicate that anti-VEGF treatment suppresses cancer progression without serious toxic effects. Various approaches for the control of cancers involving inhibition of the activity of VEGF are currently being investigated. This review considers the clinical implications of VEGF, particularly its prognostic, predictive, and therapeutic value.

Endothelial Growth Factors↗
PubMed2001

Establishment of bone marrow-derived endothelial cell lines from ts-SV40 T-antigen gene transgenic rats.

PURPOSE: Postneonatal neovascularization is thought to result exclusively from the proliferation, migration, and remodeling of fully differentiated endothelial cells (ECs). Recently, it has been reported that bone marrow contains cells which can differentiate into ECs and contribute to neoangiogenesis in adult species. In this study, we tried to establish conditionally immortalized endothelial cell lines (TR-BME) derived from rat bone marrow. METHODS: Mononuclear cells were isolated and differentiated into ECs at 37 degrees C from the bone marrow of a transgenic rat harboring temperature-sensitive SV40 large T-antigen (ts T-Ag) gene. Then, the cells were transferred and incubated at 33 degrees C, a permissive temperature for ts T-Ag. Expression of vascular endothelial growth factor (VEGF) receptor (VEGFR)-1, 2, Tie-1, 2 and von Willebrand factor (VWF) were assayed by reverse transcriptase-mediated polymerase chain reaction (RT-PCR). RESULTS: We have established three cell lines incorporating 1,1'-dioctadecyl-3,3,3',3-tetramethylindo-carbocyanine perchlorate (DiI-Ac-LDL) with a spindle shape. One of these, clone 2, strongly expressed VEGFR-2, and weakly expressed VEGFR-1 and VWF. In contrast, clone 8 showed strong expression of Tie-1, 2, and VWF, and weak expression of VEGFR-1,2. All markers were expressed strongly in clone 3. CONCLUSIONS: These data confirm that the above three TR-BME cells are novel ECs derived from bone marrow progenitors.

Animals↗
PubMed2001

Goblet cell carcinoid of the appendix: Investigation of the expression of beta-catenin and E-cadherin.

Goblet cell carcinoids are rare neoplasms that predominantly occur in the appendix. In this report we present a case of goblet cell carcinoid of the appendix. A 58-year-old male patient complaining of pain in the right lower quadrant was diagnosed with acute appendicitis and underwent an appendectomy. Histological examination of the resected appendix revealed goblet cell carcinoid. Infiltration of tumor cells beyond the appendix was observed and the surgically resected margin was positive for tumor cells. Carcinoembryonic antigen (CEA) was diffusely detected by immunohistochemistry, and cytokeratin 20, neuron-specific enolase (NSE), chromogranin A and serotonin were focally observed in the tumor cells. The expression of beta-catenin and E-cadherin was investigated to compare with that of typical rectal carcinoids (n = 3) and colon adenocarcinomas (n = 3). In normal colonic and rectal mucosae, beta-catenin and E-cadherin stained positive on the plasma membrane. In the case reported here, beta-catenin showed a preserved expression on the plasma membrane of goblet cell carcinoid; a pattern similar to typical carcinoids rather than to adenocarcinomas. However, E-cadherin demonstrated a reduced expression on the plasma membrane of the tumor cells. This staining pattern was identical to those both of carcinoids and of adenocarcinomas. These findings suggest the possibility that, in some cases, the adherens junctions of goblet cell carcinoids are similar to those of typical carcinoids rather than to those of adenocarcinomas.

Appendix↗
PubMed2001

Adult-onset herpes simplex virus hepatitis with diffuse myofibroblastic transformation of hepatic stellate cells (Ito cells) in non-necrotic areas.

The myofibroblastic transformation of hepatic stellate cells (HSC; also known as Ito cells) usually occurs following necrosis of adjacent liver cells. No report has previously found that such a transformation occurs in herpes simplex virus (HSV) hepatitis. We present an autopsy case of HSV hepatitis with myofibroblastic transformation of HSC that is different from the usual transformation of HSC. The patient was a 66-year-old woman who had received various therapies for cutaneous T-cell lymphoma. An autopsy revealed submassive hepatic necrosis with hemorrhage due to HSV hepatitis. HSV infection was confirmed by DNA in situ hybridization in liver tissue. Immunohistochemical staining for alpha-smooth muscle actin (ASMA) showed a strong positive reaction in almost all of the HSC in non-necrotic areas. However, in necrotic areas, the HSC were completely negative for ASMA. These findings indicate that not only liver cells but also HSC can become necrotic in HSV hepatitis. In contrast, in non-necrotic areas, almost all of the HSC showed active transformation to myofibroblasts.

Actins↗
PubMed2001

Malignant phyllodes tumor of the breast with expression of osteonectin and vinculin.

Phyllodes tumor is a very rare neoplasm which accounts for 2.5% of all fibroepithelial lesions of the breast. The mesenchymal component of a malignant phyllodes tumor frequently contains heterologous components. We report a case of malignant phyllodes tumor. The patient was a 40-year-old woman with a lump on the left breast. Histological examination revealed the lump to be a malignant phyllodes tumor with foci of liposarcomatous differentiation. The mesenchymal tumor cells, including those in the liposarcomatous components, were found to express vimentin, osteonectin and vinculin. However, they showed no immunoreaction to CAM 5.2, desmin, alpha-smooth muscle actin (ASMA), neuron-specific enolase (NSE) nor S-100. Ultrastructurally, the mesenchymal tumor cells were found to have abundant cytoplasmic organelles, but there was no evidence showing their differentiation to myofibroblasts. Further studies will be necessary to elucidate the significance of vinculin and osteonectin expression in malignant phyllodes tumor.

Adult↗
PubMed2001

Compound melanocytic nevus arising in a mature cystic teratoma of the ovary.

A 28-year-old woman complained of irregular menstruation. Abdominal ultrasound and magnetic resonance imaging (MRI) examinations revealed a cystic tumor in the left ovary. A histological examination of the resected ovary revealed that the lesion was a mature cystic teratoma. In this tumor, components such as skin with appendages, a thyroid gland, mucosa of the digestive tract and a submandibular gland were observed. Interestingly, compound melanocytic nevus was also present in the skin component. To the best of our knowledge, this is the sixth reported case of nevus arising in a mature cystic teratoma of the ovary. Despite the extreme rarity of such a lesion, pathologists should recognize the possibility of such lesions occurring in ovarian teratoma.

Adult↗
PubMed2001

Expression of CD9/motility-related protein 1 (MRP-1) in renal parenchymal neoplasms: consistent expression in papillary and chromophobe renal cell carcinomas.

CD9 is a glycoprotein that is abundant in hematopoietic cells. Recently, it has been reported that CD9 is also present in the human kidney. In this article, we investigated the expression of CD9 using an immunohistochemical technique. We also studied the expression of CD9 protein and messenger RNA (mRNA) in tissue samples of some renal tumors using immunoblotting and reverse-transcription polymerase chain reaction (RT-PCR) analysis. Immunohistochemically, all tumors of papillary and chromophobe renal cell carcinomas (RCCs) and oncocytomas expressed CD9. In addition, CD9 was expressed in 31 of 66 conventional RCCs and 1 of 4 collecting duct carcinomas. On immunoelectron microscopy, CD9 was identified on the plasma membrane of a conventional RCC. The presence of CD9 protein in normal kidneys and various renal tumors, except for a collecting duct carcinoma and an oncocytoma, was confirmed by immunoblotting. On RT-PCR analysis, the expression of CD9 mRNA was observed in 1 normal kidney, 2 conventional RCCs, and 1 oncocytoma. The frequency of immunohistochemical CD9 positivity was significantly higher in papillary and chromophobe RCCs than in collecting duct carcinomas and conventional RCCs, respectively. These results suggest that CD9 may be a beneficial marker in the differential diagnosis between papillary RCCs and collecting duct carcinomas and also between chromophobe and conventional RCCs.

Adult↗
PubMed2001

Dissociation of Bax from a Bcl-2/Bax heterodimer triggered by phosphorylation of serine 70 of Bcl-2.

Serine 70 in the loop region of Bcl-2 is specifically phosphorylated by paclitaxel-treatment in tumor cells and BHK cells expressing Bcl-2. The phosphorylation of serine 70 of Bcl-2 (pS70-Bcl-2) peaks 24 to 48 h after paclitaxel treatment and accelerates apoptosis. Phosphorylation is effectively inhibited in the presence of actinomycin D or cycloheximide, which restore cell viability to the same level as control cells not expressing Bcl-2. These results indicate that paclitaxel-induced kinase(s) and/or its activator(s) are synthesized de novo and play an important role in paclitaxel-induced apoptosis by phosphorylating Bcl-2. In binding assays using the phosphorylation-specific antibody against pS70-Bcl-2, the induction of serine 70 phosphorylation 70 results in a loss of the binding ability of Bcl-2 to Bax, a pro-apoptotic partner, and induces subsequent cell death. When the pS70-Bcl-2 antibody was added to human breast cancer tissue, serine 70 phosphorylation was also detected, even prior to treatment with anticancer agents. Further study of breast cancers revealed 83% of tumors with high pS70-Bcl-2 expression responded to paclitaxel or docetaxel treatment, whereas 57% of those with low expression not respond. These findings suggest that pS70-Bcl-2 might be a predictive factor for prognosis and sensitivity to paclitaxel treatment for breast cancer.

Animals↗
PubMed2001

Paxillin: application of immunohistochemistry to the diagnosis of chromophobe renal cell carcinoma and oncocytoma.

Paxillin is a cytoskeletal protein that was recently identified as a component of focal adhesions and links between F-actin and integrin. In this study, 91 renal tumors--65 conventional renal cell carcinomas (RCCs), 14 papillary RCCs, 6 chromophobe RCCs, 4 collecting duct carcinomas, 2 oncocytomas--were investigated for the immunohistochemical expression of paxillin. In a normal kidney, paxillin was predominantly expressed in the cytoplasm of distal tubules, loops of Henle, collecting ducts, and vascular smooth muscle cells. In all of the chromophobe RCCs and oncocytomas, strong expression of paxillin was observed in the tumor cytoplasm. In contrast to these tumors, conventional RCCs, papillary RCCs, and collecting duct carcinomas showed negative reactions for paxillin except for one case in each subgroup with weak reactivity. An immunoblot analysis confirmed the presence of paxillin in healthy kidney, chromophobe RCC, and oncocytoma. These data suggest that paxillin possibly plays a role in signal transductions as a focal adhesion intervening between tumor cells and the extracellular matrix in renal tumors with collecting duct phenotypes such as chromophobe RCCs and oncocytomas, but not in conventional RCCs. In addition, paxillin may be an available marker in distinguishing chromophobe RCCs from conventional or papillary RCCs.

Adenoma, Oxyphilic↗