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Biomedical subjects

M Tsuneyoshi

Publications and source records attributed to M Tsuneyoshi.

At least 127 records · Page 7Linked to original sources

Expressions of basic fibroblast growth factor and fibroblast growth factor receptor mRNA in soft tissue tumors by in situ hybridization.

Basic fibroblast growth factor (bFGF) is a mitogenic and angiogenic polypeptide produced by diverse cell types, including the cells derived from normal tissue and neoplastic lesions. To evaluate the possible differential expression of bFGF in soft tissue tumors, we examined 17 frozen primary soft tissue tumors including extra-abdominal desmoids, leiomyosarcomas, synovial sarcomas, myxoid liposarcomas, and alveolar soft part sarcomas by nucleic acid in situ hybridization. Three of the four leiomyosarcomas and two of the three synovial sarcomas studied expressed bFGF mRNA, whereas all of the myxoid liposarcomas and alveolar soft part sarcomas were negative. Two of the leiomyosarcomas were also positive for FGF receptor mRNA. These results indicated the possibility of an autocrine or paracrine mechanism in the function of bFGF and also lent support to the opinion that in situ hybridization is useful for examining cell character.

Adolescent↗

Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human osteosarcoma.

The Y-box-binding protein, YB-1, is a member of the DNA-binding protein family. It binds to the Y-box, an inverted CCAAT box, in the promoter region of the human multidrug resistance 1 gene, which encodes P-glycoprotein (P-gp). Nuclear localization of YB-1 protein has been reported to be associated with the intrinsic expression of P-gp in human breast cancer. We studied the immunohistochemical expression of YB-1 protein in 69 untreated biopsy specimens of conventional osteosarcomas and compared it with the expression of P-gp. Furthermore, cell proliferation, as determined by the MIB-1-labeling index (MIB-1-LI), was measured by immunohistochemistry. In all 69 untreated osteosarcomas, YB-1 protein was expressed in the cytoplasm. In 32 of 69 (46%) cases, YB-1 was also localized in the nucleus. The expression of P-gp was evident in 23 of these 32 cases, and there was a significant correlation between the nuclear expression of YB-1 and P-gp expression (P < 0.0001). Chondroblastic osteosarcoma expressed YB-1 in the nucleus more frequently (eight of nine cases) than did other types of osteosarcoma, whereas P-gp was also frequently expressed in chondroblastic subtype. There was no correlation between the nuclear expression of YB-1 and histological grade. The MIB-1-LI was significantly higher in cases showing the nuclear expression of YB-1 (MIB-1-LI averaged 22.56 in cases with only cytoplasmic expression of YB-1 but averaged 28.20 in cases with cytoplasmic and nuclear expression of YB-1; P = 0.0477). In human osteosarcoma, nuclear localization of YB-1 protein was associated with the expression of P-gp, suggesting that YB-1 could be a prognostic marker for multidrug resistance in osteosarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

N-myc gene amplification in rhabdomyosarcoma detected by fluorescence in situ hybridization: its correlation with histologic features.

Fluorescence in situ hybridization (FISH) was applied to 15 alveolar rhabdomyosarcomas (A-RMSs) and 14 embryonal RMSs (E-RMSs) to detect N-myc (also called MYCN) oncogene amplification. The results were compared with histologic characteristics and clinical factors. The number of surviving patients in each subtype was 5 of 15 with A-RMS and 5 of 14 with E-RMS. N-myc amplification was detected in 9 of the 15 A-RMSs but in none of the 14 E-RMSs. Tumor cells exhibiting N-myc amplification were identified only in the alveolar area in two A-RMSs, and they demonstrated a histologic mixture of alveolar and embryonal patterns. The remaining seven cases with an amplified N-myc showed a conventional alveolar pattern. Among the 15 A-RMSs, the survival rate of patients with tumors showing nonamplified N-myc and amplified N-myc oncogene was 4 (66%) of 6 and 1(11%) of 9, respectively (P < .05). No significant difference was observed between the other clinical findings (age, primary sites, clinical stages) of the N-myc-amplified and nonamplified tumors. Therefore, we concluded that the N-myc gene amplification, which is characteristic of a particular subtype of A-RMS, might be useful as a prognostic factor for an unfavorable outcome.

Adolescent↗

Induction of chronic inflammatory arthropathy and mesenchymal tumors in rats infected with HTLV-I.

To compare the pathogenicity of HTLV-I derived from patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) and that from patients with adult T-cell leukemia (ATL), neonatal WKA rats were inoculated with either an HTLV-I-infected T-cell line (Fuk line) newly established from a HAM/TSP patient or MT-2 derived from a patient with ATL. Of 38 rats, 34 developed mesenchymal tumors (89%) only after 14 months of age, irrespective of the cell lines used. The rats inoculated with the Fuk line developed severe arthritis (27%) and anti-type II collagen antibody (64%), and less frequently, paraparesis (7%). Those inoculated with MT-2 developed paraparesis (23%), but not arthritis. Cyclophosphamide (CY) administration to induce immunosuppression in the Fuk line-inoculated rats increased the frequency of paraparesis (70%), but decreased the frequency of tumors (20%). HTLV-I proviral DNA was found in the spinal cord, sciatic nerves, tumors, and joints, whereas pX mRNA was detected in the sciatic nerves and tumors, but not in the spinal cord and joints. As a result, HTLV-I is considered to facilitate development of both chronic inflammatory arthropathy associated with autoimmunity and mesenchymal tumors in rats by experimental infection, and its pathogenicity is likely to be greatly influenced by the host immune state.

Animals↗

Establishment and characterization of a new synovial sarcoma cell line, SN-SY-1: special reference to bcl-2 protein and SYT-SSX1 hybrid transcripts.

We established and characterized a new human synovial sarcoma cell line, SN-SY-1, derived from a monophasic fibrous synovial sarcoma excised from the abdominal wall of a 21-year-old man. We maintained the cell line for over 35 passages in vitro. The SN-SY-1 cells in vitro exhibit spindle and polygonal shapes and join to form an epithelial plaque. SN-SY-1 maintained a consistent karyotype: 46,t(X;18)(p11.2;q11.2), Y, t(6;8) (q13-15;q11-13), the same as that of the primary tumor specimen. RT-PCR assay for chimeric SYT-SSX transcripts followed by digestion with restriction enzymes revealed SYT-SSX1 fusion protein. An immunohistochemical study revealed expression of bcl-2 protein in the SN-SY-1 cell line, in vitro and in vivo. However, DNA analysis showed no rearrangement of the bcl-2 gene, and expression of bcl-2 mRNA was low. Why bcl-2 protein was expressed in this synovial sarcoma was not clarified.

Abdominal Neoplasms↗

Angiogenesis in endometrial carcinoma.

BACKGROUND: Tumor angiogenesis is essential for tumor growth and metastases. Recently, microvessel density (MVD), a measure of tumor angiogenesis, has been found to have prognostic significance for predicting metastasis and survival in many tumor types. This study was conducted to determine how MVD was related to several clinicopathologic parameters and correlated with metastasis and survival in patients with endometrial carcinoma. METHODS: From 1979 through 1989, 85 cases of clinical Stage I and II endometrial carcinomas treated initially by hysterectomy with pelvic lymph node dissection were reviewed histologically. All hysterectomy specimens were stained immunohistologically for factor VIII-related antigen. MVD was counted in a x200 field (x20 objective lens and x10 ocular lens, 0.785 mm2 per field) in the most active area of neovascularization. Results were expressed as the highest number of microvessels identified within any single x200 field. Statistical analysis included the Mann-Whitney U test, Kruskal-Wallis test of variance, and the Spearman rank correlation test. Survival was calculated using the Kaplan-Meier method and differences in survival were analyzed using the log rank test. MVD and several other prognostic parameters were examined for their correlation with progression free survival (PFS) and overall survival (OS) by a multivariate analysis according to the Cox proportional hazards model. RESULTS: MVD was significantly correlated with tumor grade (P = 0.0281), myometrial invasion (P = 0.0282), and lymph-vascular space invasion (P = 0.0073). There was no correlation between microvessel count and lymph node status and stage. Patients with a high MVD (> or =60) had significantly worse PFS and OS than those with a low MVD (<60) (log rank test, P = 0.0116 and P = 0.0096, respectively). Multivariate analysis showed that MVD correlated significantly and independently with PFS and OS. CONCLUSIONS: In this study, MVD was found to be an independent prognostic factor for PFS and OS in patients with endometrial carcinoma.

Adult↗

Adenosquamous carcinoma of the liver: clinicopathologic characteristics and cytokeratin profile.

BACKGROUND: The clinicopathologic characteristics, biologic behavior, and histogenesis of primary adenosquamous carcinoma (ASC) of the liver have yet to be fully clarified. METHODS: Eight cases of ASC of the liver were analyzed both clinicopathologically and immunohistochemically using antibodies of cytokeratin (CK) 7, CK 8, CK 18, CK 19, and CK 903 (CK 5, CK 10, CK 11, and CK 14). The survival curve of the 6 patients with surgically resected ASC was compared with that of the 32 patients with common cholangiocarcinoma (CC). RESULTS: Most ASCs had invasive pathologic features, including venous invasion, lymphatic permeation, and intrahepatic metastases. There were lymph node metastases from 7 tumors (88%), and most of the metastases were adenocarcinoma. All adenocarcinoma (AC) components were positive for both CK 7 and CK 19. The squamous cell carcinoma (SCC) components were positive for CK 7 in all cases but were positive for CK 19 in only 5 cases (62.5%). The ACs were positive for CK 903 in only 3 cases (37.5%), whereas all SCCs were positive for CK 903. Almost all ACs were positive for both CK 8 and CK 18, whereas the SCCs were positive for CK 8 in only 3 cases (37.5%) and for CK 18 in no cases. All 6 patients with surgically resected ASC died of the disease within 1 year postoperatively. Their survival curve was significantly worse than that of the 32 patients with common CC (P < 0.001). The two patients on whom autopsy was performed also died within 1 year after diagnosis. CONCLUSIONS: ASC tended to have more aggressive biologic behavior and a poorer prognosis than common CC. The authors' immunohistochemical analysis of CK expression indicated that most of the ASCs of the liver that were studied developed from a squamous transformation of the preexisting CC.

Aged↗

Synchronous and metachronous primary gastric lymphoma and adenocarcinoma: a clinicopathological study of 12 patients.

BACKGROUND: The occurrence of both malignant gastric lymphoma and adenocarcinoma in the same patient is very rare. METHODS: The resected specimens from 12 patients who had both primary gastric lymphoma and adenocarcinoma were analyzed using immunohistochemistry and in situ hybridization. RESULTS: Two different tumors were found synchronously in 10 patients (5 with independent tumors and 5 with contiguous/collision tumors) and metachronously in 2. The size of the lymphomas (mean, 7.2 cm) was larger than that of the adenocarcinomas (mean, 3.6 cm) (P < 0.005). Histologically, 9 of the 12 lymphomas (75%) were mucosa-associated lymphoid tissue lymphomas, and all lymphomas invaded the deep portion of the submucosa or deeper. Conversely, 10 of the 12 adenocarcinomas (83%) were early carcinomas. Six adenocarcinomas were intestinal type, whereas the other 6 were diffuse type. The MIB-1 index of the adenocarcinomas (mean, 50.4%) was higher than that of the lymphomas (mean, 29.3%) (P < 0.05). Helicobacter pylori (H. pylori) was documented in all 12 patients, whereas Epstein-Barr virus-encoded RNA 1 was detected in only 2. During the follow-up period after surgery, 6 patients died, 4 due to adenocarcinoma. The survival probability of all 12 patients appeared to be similar to that of previously reported patients with gastric adenocarcinoma alone, and was significantly worse than that of the 217 patients with gastric lymphoma alone (P < 0.05). CONCLUSIONS: An H. pylori infection is considered to be associated with the development of these double malignancies. In many such synchronously observed cases, lymphomas may precede carcinogenesis, while the prognosis appears to be more closely associated with the adenocarcinoma than the lymphoma.

Adenocarcinoma↗

Helicobacter pylori and primary gastric lymphoma. A histopathologic and immunohistochemical analysis of 237 patients.

BACKGROUND: Few previous articles have analyzed the relation between infection with Helicobacter pylori (H. pylori) and primary gastric lymphoma in a large number of patients. METHODS: Resected and biopsied specimens from 237 patients with primary gastric lymphoma were investigated for H. pylori using hematoxylin and eosin stain, modified Giemsa stain, and immunohistochemistry. These specimens were compared with specimens from 29 patients with chronic active gastritis, 33 with peptic ulcers, and 41 with gastric carcinoma. RESULTS: H. pylori was detected in 145 of 237 patients (61%) with gastric lymphoma. The frequency of H. pylori positivity was higher in patients with lymphoma restricted to the mucosa and submucosa (76%) than in those with lymphoma invading beyond the submucosa (48%) (P < 0.001), and was also higher in patients with low grade mucosa-associated lymphoid tissue lymphoma (72%) than in those with high grade tumors (55%) (P < 0.05). The frequency of H. pylori positivity in patients with lymphoma was lower than in those with chronic active gastritis (100%) (P < 0.001) or peptic ulcer (91%) (P < 0.05). In patients with lymphoma restricted to the mucosa and the superficial portion of the submucosa, the frequency of H. pylori positivity (90%) was as high as that observed in patients with chronic active gastritis and peptic ulcer. The H. pylori grading score for patients with lymphoma (0.9 +/- 1.0) was lower than for those with chronic active gastritis (1.9 +/- 0.8) (P < 0.001), peptic ulcers (2.2 +/- 1.0) (P < 0.001), or gastric carcinoma (1.2 +/- 1.1) (P < 0.05). CONCLUSIONS: These results suggest that H. pylori is more likely to be associated with early states of primary gastric lymphoma than with advanced states. Thus, H. pylori may disappear during the progression of primary gastric lymphoma.

Adolescent↗

Reliability of frozen section diagnosis of gallbladder tumor for detecting carcinoma and depth of its invasion.

BACKGROUND: An accurate frozen section diagnosis is important when deciding the surgical strategy against a gallbladder tumor intraoperatively. Little has been reported on the accuracy of frozen section diagnosis of the gallbladder. PATIENTS AND METHODS: In a total of 86 consecutive patients with gallbladder tumor, the accuracy of the frozen section diagnosis was examined. There were 32 patients with polypoid lesions and 54 with nonpolypoid tumors. RESULTS: The frozen tissue diagnosis and final diagnosis were identical in 82 of the 86 cases, that is, benign in 65 and malignant in 17. The other four cases had different diagnoses, that is, conversion from benign to malignant in two and from malignant to benign in two. The overall accuracy of frozen diagnosis was 95.3% (97.0% for benign and 94.7% for malignant). In 32 polypoid lesions, the accuracy of frozen section diagnosis was 91% (93% for benign; 89% for malignant). In 54 nonpolypoid lesions, the accuracy of diagnosis was 98% (100% for benign; 93% for malignant). The diagnosis of depth of invasion was identical only in 7 (70%) of the 10 carcinoma cases examined, while it was diverse in the remaining 3, that is, conversion from adenocarcinoma invading the subserosa to that limiting to the mucosa in one, from carcinoma within the mucosa to that infiltrating the muscle coat in one, and from carcinoma affecting the muscle layer to that invading the subserosa in the other. Alterations of frozen section diagnosis about being benign or malignant and about the depth of invasion were encountered in seven patients, five of whom had a polypoid tumor. CONCLUSIONS: The intraoperative frozen tissue diagnosis is fairly reliable as to whether lesions are malignant or benign; however, accuracy is low in patients with polypoid lesions of the gallbladder. Also, frozen section diagnosis does not reliably measure the depth of invasion of gallbladder carcinoma.

Adenocarcinoma↗

The prognostic value of semiquantitative nuclear grading in endometrial carcinomas.

The objective of this study was to evaluate the prognostic value of a convenient nuclear grading system based on only the proportion of nuclei measuring more than 10 microm in length at the shortest axis in endometrial carcinomas. Of the 235 cases reviewed, 9 serous and 5 clear cell adenocarcinomas and 2 small cell carcinomas were eliminated, resulting in a study population of 219 cases of endometrial adenocarcinoma. The architectural grade was determined by the FIGO system. The criteria for nuclear grade were as follows: grade 1, no nucleus measuring more than 10 microm in length at the shortest axis; grade 2, nuclei measuring more than 10 microm in length at the shortest axis seen in percentages ranging between 0 and 10% of tumor cells in active areas; and grade 3, more than 10% of tumor cells in active areas with nuclei measuring more than 10 microm in length at the shortest axis. The criteria for combined grades were as follows: the tumors were graded according to the architectural grade, but high-grade nuclear abnormalities increased the grade by one for architectural grade 1 and 2 tumors. The cumulative 10-year survival rates for architectural grades 1, 2, and 3 were 92.4, 82.6, and 65.2%, respectively (chi2 = 17.9, P = 0.001). The survival rates for nuclear grades 1, 2, and 3 were 96.2, 76.1, and 70.1%, respectively (chi2 = 21.6, P < 0.001), while for combined grades 1, 2, and 3 the survival rates were 98.3, 83.2, and 65.2%, respectively (chi2 = 26.9, P < 0.001). Even when the cases were limited to the 147 stage I endometrial carcinomas examined, the prognostic value of the combined grading system was still found to be superior to that of the architectural grading system. Our observations therefore supported the FIGO recommendation for nuclear grade not only in stage I endometrial carcinomas, but also in all stages of endometrial carcinomas.

Adenocarcinoma, Clear Cell↗

Significance of the expression of proliferation-associated nucleolar antigen p120 in human colorectal tumors.

Nucleolar protein p120 is considered to be associated with cell proliferation and has also been detected in a broad range of human malignant cells and tissues, but not in either normal resting tissue or most benign tumors. To clarify the significance of the expression of p120 in colorectal tumors or to evaluate the contribution of p120 in the development of colorectal carcinoma, the authors developed a monoclonal antibody against p120 and then examined its expression in adenoma, carcinoma, and normal mucosa. In adenomas, p120 expression was shown in none of 13 cases of mild dysplasia (0%), 2 of 15 of moderate dysplasia (13.3%), and in 2 cases of severe dysplasia (100%). p120-positive adenomas of moderate dysplasia tended to be larger and had higher Ki-67 indexes than the negative ones (adenomas of moderate dysplasia). All 27 carcinomas were positive for p120. p120 immunostaining was found in the nuclei and corresponded closely to the prominent nucleoli of tumor cells. In contrast, either weak or the occasional expression of p120 was traced in only one of the nine normal mucosae (11.1%). Three of the transitional mucosae of the carcinoma were also positive for p120. The percentage of p120-positive tumor cells (p120 index) ranged from 3.2% to 86.6%, and the mean p120 indexes of the four adenomas and all carcinomas were 21.3% and 41.5%, respectively. The p120 index was significantly related to the Ki-67 index (P < .001) in the p120-positive tumors, whereas the p120 index of the carcinoma did not significantly correlate to the known prognostic markers, such as tumor size, stage, or the degree of differentiation. These results thus suggest that the expression of p120 serves as a marker for cells with a high proliferative potential and is linked to the late events of colorectal tumor progression.

Adenoma↗

Intra-articular fibroma of tendon sheath in the temporomandibular joint.

Fibroma of tendon sheath is an uncommon soft tissue tumor. The first case involving the temporomandibular joint is reported here. The patient presented with chronic clicking, pain, and swelling of the right temporomandibular joint associated with restricted jaw opening. Histologic, immunocytochemical, and ultrastructural features of the intra-articular tumor were identical to fibroma of tendon sheath. The variability of symptoms and the diagnostic problems presented by this tumor are discussed.

Actins↗

Improved prognosis of solid-type poorly differentiated colorectal adenocarcinoma: a clinicopathological and immunohistochemical study.

AIMS: We rarely encounter solid-type poorly differentiated colorectal carcinoma, and their histogenesis and biological behaviour are not fully disclosed. METHODS AND RESULTS: A review of 60 poorly differentiated carcinomas of the colorectum was undertaken, 36 (59%) of which were located in the right side of the colorectum. Although, on the basis of the World Health Organization (WHO) classification solid carcinomas are included among undifferentiated carcinomas, the poorly differentiated carcinomas were divided into four types; 27 solid carcinomas (Sol.), 17 poorly differentiated adenocarcinomas (PDA), six signet-ring cell carcinomas (Sig,) and 10 mucinous carcinomas (Muc.). Solid carcinomas revealed a solid alveolar growth of fairly uniformly sized tumour cells with occasional mitotic figures. This type of tumour had a relatively lower percentage of lymphatic permeation and lymph node metastasis compared with the other three types. The 5-year survival rates were 31% for all poorly differentiated carcinomas, 47% for the Sol. type, 32% for the PDA type, and 0% for both the Sig. and the Muc. types, with a rate of 72% for well-differentiated adenocarcinomas selected as controls. Immunohistochemically, bcl-2 protein expression was demonstrated in 38% of the Sol. type, but in only 12% of the other three non-solid types, this difference being significant (P < 0.05). CONCLUSIONS: These findings suggest that solid carcinomas of the colorectum should be regarded as a distinct type of poorly differentiated carcinoma, leading to a good prognosis.

Adenocarcinoma↗

Fibrosarcoma versus cellular fibroma of the ovary: a comparative study of their proliferative activity and chromosome aberrations using MIB-1 immunostaining, DNA flow cytometry, and fluorescence in situ hybridization.

We retrospectively analyzed the proliferative activity and the centromeric copy number of chromosomes 8, 12, and 17 in three cases of fibrosarcoma and eight cases of cellular fibroma of the ovary using MIB-1 immunostaining, DNA flow cytometry, and fluorescence in situ hybridization (FISH) on paraffin-embedded tissue specimens. In our study, both the MIB-1 labeling index (LI) and the proliferative index (% of cells in S + G2 + M phase) in fibrosarcomas were higher than those in cellular fibromas. The FISH analysis demonstrated the sole abnormality of a gain of trisomy 12 cells in all eight cases of cellular fibroma. Both a gain of trisomy 12 cells and a gain of tetrasomy 12 cells were observed in one case of fibrosarcoma. A gain of trisomy 8 cells was observed in all two fibrosarcomas in which signals were detected. By contrast, neither a gain of trisomy 8 cells nor a gain of tetrasomy 12 cells was observed in any of the eight cases of cellular fibroma. Chromosome 17 showed disomy in all eleven cases. On the basis of these findings, a gain of trisomy 8 cells is therefore considered to be an adequately effective marker to distinguish between cellular fibroma and fibrosarcoma of the ovary, and it may also be related to the proliferative activity of fibrosarcoma of the ovary.

Adolescent↗

Subcellular localization of Bcl-2 protein in synovial sarcoma.

The subcellular localization of Bcl-2 protein in surgically resected, fixed-frozen tissue specimens of seven tumors from six cases of synovial sarcoma and a synovial sarcoma cell line was examined using laser-scanning confocal microscopy and immunoelectron microscopy. Bcl-2 protein in synovial sarcoma cells was detected in the nuclear envelope, endoplasmic reticulum membrane, and mitochondrial circumference. Based on the finding of pre-embedding immunoelectron-microscopy observation, the distribution of Bcl-2 protein in such membranous organella was patchy. A computer-based image analysis failed to reveal any quantitative differences between the inner and the outer mitochondrial membranes. The tumorigenesis of synovial sarcoma is also discussed from the viewpoint of Bcl-2 overexpression.

Adult↗