Primary hyperparathyroidism with multiple osteosclerotic lesions of the calvarium.
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Adult↗
Biomedical subjects
Tetsuro Ishikawa
Publications and source records attributed to Tetsuro Ishikawa.
Very low incidence of microsatellite instability in intraductal papillary-mucinous neoplasm of the pancreas.
Intraductal papillary-mucinous carcinoma (IPMC) of the pancreas, a new entity of pancreatic cancer with a favorable prognosis, has shown a gradual increase in the number of reported cases. Patients with high-frequency microsatellite instability (MSI-H) tumors have been shown to survive longer than those with low-frequency MSI (MSI-L) or microsatellite stable (MSS) tumors in colorectal and gastric cancer. We investigated whether MSI-H in patients with IPMC can contribute to a good prognosis. The formalin-fixed paraffin-embedded tumors and surrounding normal pancreatic tissues from 10 patients with IPMCs and 16 with intraductal papillary-mucinous adenomas (IPMAs) were provided for DNA extraction after microdissection. Polymerase chain reaction (PCR) was carried out using 8 microsatellite primer marker sets. The mixed PCR samples were analyzed using a genetic analyzer. MSI-H was determined by assessment of microsatellite variations in 3 or more of the 8 tested markers. Immunohistochemical staining of the MSI-responsible proteins hMLH1 and hMSH2 was conducted for both the IPMC and IPMA samples. Ten percent of IPMC harbored MSI-H tumors, whereas no MSI-H tumors were detected in the IPMAs. Thirty percent of IPMC tumors and 25% of IPMA tumors showed MSI-L. All IPMCs and IPMAs showed normal expression of both hMLH1 and hMSH2. MSI-H and loss of hMLH1 and hMSH2 are very rare events in both IPMCs and IPMAs. We conclude that a good prognosis for patients with IPMC is not associated with MSI-H.
Adaptor Proteins, Signal Transducing↗
Establishment and characterization of OCUT-1, an undifferentiated thyroid cancer cell line expressing high level of telomerase.
BACKGROUND & OBJECTIVES: Undifferentiated thyroid cancer is one of the most aggressive human malignancies, and the prognoses that have been reported are extremely poor. A number of studies have described the clinicopathologic features of this tumor and analyzed its biologic background to explain the extraordinarily aggressive nature of the tumor. Still the mechanism of cellular aggressiveness in undifferentiated thyroid cancer is not yet fully understood. METHODS: We established and characterized an undifferentiated thyroid cancer cell line, OCUT-1, derived from the surgical specimen obtained from a 74-year-old Japanese woman with advanced undifferentiated thyroid cancer. RESULTS: The cell line had already maintained over 100 passages and was stably cultured for more than a year. The cell line was observed to maintain not only its morphologic similarity to the primary cancer cells, but also its aggressive nature, including high proliferative activity, numerous genetic abnormalities, and cytokine production. Further, we have demonstrated the expression of telomerase activity in the cell, which could represent one of the responsible mechanisms for the cellular aggressiveness of this type of tumor. CONCLUSIONS: This cell line might be useful for further study concerning the correlation between telomerase activation and disease progression or anaplastic change in thyroid cancer.
Aged↗
Primary leiomyosarcoma of the breast: report of a case.
We describe herein a case of primary leiomyosarcoma of the breast in a 59-year-old woman. Preoperative clinical examination and cytology findings indicated a benign breast tumor, but intraoperative histopathological examination of the tumor revealed malignant spindle cells, and a modified radical mastectomy was performed. Immunohistochemical analysis subsequently confirmed a diagnosis of leiomyosarcoma. Primary leiomyosarcoma of the breast is extremely rare and difficult to diagnose before surgery because of the need for mitotic figures and immunohistochemical staining to confirm the diagnosis. When pre- and intraoperative examinations indicate the possibility of a leiomyosarcoma, an extended excision with sufficient margins should be performed to remove all of the affected tissue. A review of the literature on this unusual tumor of the breast is presented.
Breast Neoplasms↗
Thoracoscopic excision for ectopic mediastinal parathyroid tumor.
Ectopic parathyroid adenoma or hyperplasia in the mediastinum are seen in a percentage of patients with hyperparathyroidism and have generally been treated by conventional open surgery. However, due to recent improvements in the ability of diagnostic imaging such as 99mTc-methoxyisobutylisonitrile (MIBI) scintigraphy to identify these lesions, we have been obtaining favorable results from thoracoscopic excision of mediastinal parathyroid tumors. In thoracoscopic surgery, three to four trocars were inserted between the fourth and seventh ribs from a lateral approach. Based on diagnostic imaging, tumors were identified and excised by the shortest possible route. Surgery time for four consecutive patients ranged from 50 to 140 min, and hemorrhage volumes were small. No intra- or postoperative complications were observed, and the postoperative course for these patients has been uneventful. Analgesia was required only a few times for each patient. In the most recent patient, radioisotope-navigated thoracoscopic excision was performed using 99mTc-MIBI. When thoracoscopic excision was combined with radioisotope navigation, tumor identification took less time, cutting the surgery time in half and ultimately placing less stress on the patient.
Adult↗
Radioisotope-navigated video-assisted thoracoscopic operation for ectopic mediastinal parathyroid.
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Choristoma↗
Peroxisome proliferator-activated receptor gamma activation induces cell cycle arrest via the p53-independent pathway in human anaplastic thyroid cancer cells.
Anaplastic thyroid carcinoma is one of the most aggressive human malignancies. Outcomes of intensive multimodal therapy have been far from satisfactory. Furthermore, p53 gene dysfunction, often found in this type of cancer, is known to impair the efficacy of the therapeutic agents. Specific ligands for peroxisome proliferator activated receptor gamma (PPAR-gamma) induce growth suppression in some tumor cells. In this study, we investigated the role of PPAR-gamma in anaplastic thyroid cancer cell lines (OCUT-1, ACT-1). PPAR-gamma was expressed and functional in both cell lines. Activation of PPAR-gamma with its specific ligands, troglitazone and 15-deoxy-delta 12,14-prostaglandin J2, inhibited cell growth in a dose-dependent manner through inducing G1 cell cycle arrest. P53 protein expression differed in OCUT-1 and in ACT-1, though the levels stayed constant irrespective of ligand exposure in both cell lines. In contrast, p21 and p27 proteins were induced in a dose-dependent manner in both situations. This study showed that PPAR-gamma ligands were able to induce growth suppression in anaplastic thyroid cancer cells via a p53-independent, but p21- and p27-dependent cytostatic pathway. These tumor-suppressive effects of PPAR-gamma may provide a novel approach to the treatment of anaplastic thyroid cancer.
Cell Cycle↗
Prognostic value of microsatellite instability in resectable pancreatic cancer.
The significance of microsatellite instability (MSI) as a prognostic predictor for resectable pancreatic cancer patients was examined. Forty-six histologically confirmed pancreatic cancer patients who had undergone resection were studied. DNA was extracted from the paraffin block sections by means of the microdissection method. PCR was performed using eight microsatellite primer marker sets. The mixed PCR sample was analyzed by a genetic analyzer. The number of MSI-positive patients was eight (17.4%) as determined by assessment of microsatellite variations in three or more of the eight tested markers. Univariate analysis revealed that patients with MSI-positive tumors had significantly longer survival times than patients with MSI-negative tumors, although there were no significant differences in clinicopathological factors between the two groups (median survival term, 62 months versus 10 months, respectively; P = 0.011). According to univariate survival analysis, patients with T3/T4, N1, or M1 tumors, as classified by Union Internationale Contre le Cancer staging, had significantly shorter survival times than patients with less progressive tumors. Multivariate survival analysis indicated that MSI status had an independent predictive value (hazard ratio = 5.577; P = 0.007). The tumor-infiltrating leukocyte intensity in MSI-positive tumors was significantly larger than that in MSI-negative tumors, suggesting that MSI-positive tumors may induce stronger antitumor immunity. In conclusion, a patient with MSI-positive pancreatic cancer may have a comparatively better prognosis after resection, possibly due to intensive immunoreaction to the tumor.
Aged↗
Genetic alterations in adenoma-carcinoma sequencing of intraductal papillary-mucinous neoplasm of the pancreas.
We investigated the adenoma-carcinoma sequence in intraductal papillary-mucinous neoplasm from the aspect of genetic changes. The formalin-fixed paraffin-embedded tumors and surrounding normal pancreatic tissues from patients with 16 intraductal papillary-mucinous adenoma of the pancreas (IPMA) and 10 intraductal papillary-mucinous carcinoma of the pancreas (IPMC) were provided for DNA extraction after microdissection. SSCP-DNA sequencing analysis demonstrated K-ras mutations at codon 12 in 75% of IPMA and 70% of IPMC, while those at codon 13 were observed neither in IPMA nor IPMC. There were no characteristic K-ras mutation types in IPMA and IPMC and no significant differences in incidence of K-ras mutations between the two categories. The frequencies of p53 mutations analyzed by SSCP-DNA sequencing were not high in IPMA (18.8%) and IPMC (30%), showing no significant difference between them. LOHs of APC in IPMA and IPMC were infrequent (6.3 and 20%, respectively) and showed no significant difference in incidence between the two categories. The LOH frequencies of DCC in IPMA and IPMC were 31.3 and 40%, respectively, and were not statistically different from each other. Taken together, genetic changes such as K-ras, p53, APC and DCC mutations may not be associated with adenoma-carcinoma sequence in intraductal papillary-mucinous neoplasm of pancreas.
Adenocarcinoma, Mucinous↗
Decrease in ICAM-1 expression on gastric cancer cells is correlated with lymph node metastasis.
BACKGROUND: Lymph node metastasis is a frequent type of metastasis in patients with gastric cancer. The mechanisms responsible for this type of metastasis, however, are not clearly understood. We hypothesize that the immunosurveillance system between cancer cells and lymphocytes may be associated with the lymph node metastatic process. In this study, we examined the correlation between lymph node metastasis and intercellular adhesion molecule-1 (ICAM-1), which mediates the immunosurveillance system between tumor cells and cytotoxic lymphocytes, in gastric cancer.METHODS: One hundred and forty-three specimens resected from patients with gastric cancer were investigated by staining with a monoclonal antibody against ICAM-1. We studied the correlation between the expression of ICAM-1 and various clinicopathologic factors, as well as infiltration of tumor-infiltrating lymphocytes (TILs).RESULTS: ICAM-1 expression on gastric cancer cells was significantly decreased in patients with lymph node metastasis. The infiltration of TILs was associated with ICAM-1 expression level. The prognosis of patients with ICAM-1-negative tumors was poorer than the prognosis of those with ICAM-1-positive tumors.CONCLUSIONS: These findings suggest that ICAM-1 expression on cancer cells is closely associated with lymph node metastasis in gastric cancer, under the influence of the host immunosurveillance system.
Journal Article↗
Expression of intercellular adhesion molecule-1 and prognosis in colorectal cancer.
Intercellular adhesion molecule-1 (ICAM-1) is a 90-kDa cell surface glycoprotein and is known to be a member of the immunoglobulin gene superfamily of adhesion molecules. It has been suggested that ICAM-1 expression on cancer cells might have a role as a suppressor of tumor progression under the host immune surveillance system. We studied the correlation between the expression of ICAM-1 and clinicopathological factors, as well as infiltration of tumor infiltrating lymphocytes (TILs) in colorectal cancer. Resected specimens from 96 patients with colorectal carcinoma were investigated using immunohistochemical staining with a monoclonal antibody against ICAM-1. As a result, the incidence of lymph node or liver metastasis was significantly lower in patients with ICAM-1-positive tumors than in those with ICAM-1-negative tumors. Infiltration of TILs was more frequently observed in the ICAM-1-positive tumors than in the ICAM-1-negative tumors. The prognosis of the patients with ICAM-1-negative tumors was significantly poorer than that of those with ICAM-1-positive tumors. In conclusion, these findings suggested that ICAM-1 expression is closely associated with metastasis and may be a useful indicator of prognosis in patients with colorectal cancer.
Adult↗
Prognostic value of combined analysis of estrogen receptor status and cellular proliferative activity in breast cancer patients with extensive lymph node metastases.
Breast cancer patients with four or more lymph node metastases generally show poor prognosis. However, some can survive for a long period. In this study, we retrospectively evaluated these cases for estrogen receptor status and cell proliferation potential in an attempt to predict patient outcome more accurately. Ninety-two radically operated primary breast cancer patients with four or more lymph node metastases were examined. High PCNA LI and ER-negative status were significantly associated with poor outcome. Then, survival analysis was performed on combination of ER and PCNA LI status, remarkable difference was shown in the prognosis of the patients.
Breast Neoplasms↗
Negative hMSH2 protein expression in pancreatic carcinoma may predict a better prognosis of patients.
The prognostic values of immunohistochemical staining for hMSH2 and hMLH1 in patients with pancreatic carcinomas were investigated. Fifty-five patients with histologically proven pancreatic carcinomas were studied. Immunohistochemical staining for hMSH2 and hMLH1 was performed by avidin-biotin-peroxidase complex method with a catalyzed signal amplification system. Tumor cells that exhibited an absence of nuclear staining in the presence of non-neoplastic cells with nuclear staining were considered to have an abnormal pattern. Four tumors (7.3%) demonstrated abnormal hMS2-negative staining. One tumor (1.8%) had abnormal hMLH1-negative staining and this tumor showed negative hMSH2 staining. No particular clinicopathologic factor such as tumor location, histology, T-factor, N-factor and TNM-stage were observed in patients with negative hMSH2 staining tumors. Median survival time (MST) of patients with hMSH2-negative tumors was comparatively longer than that of patients with hMSH2-positive tumors, however, there was no significant difference between MSTs of the two groups (56 months vs. 14 months; p=0.16). We concluded that negative hMSH2 immunohistochemical staining in the pancreatic carcinomas may demonstrate certain patients, but not all, who had microsatellite instability-positive tumors. The patients with hMSH2-negative tumors may have better prognoses than those with hMSH2-positive tumors. To clarify these findings, further large number of pancreatic carcinomas must be investigated.
Adaptor Proteins, Signal Transducing↗
Oral UFT and cyclophosphamide combination chemotherapy for metastatic breast cancer.
BACKGROUND: Effective long-term chemotherapy yielding good quality of life is essential. The clinical benefits of oral UFT and cyclophosphamide (CPA) combination chemotherapy for metastatic breast cancer (MBC) were evaluated. PATIENTS AND METHODS: Twenty cases with MBC were enrolled. The mean age was 54 years. Five cases had loco-regional and others had distant metastasis. Nineteen cases had previous therapies. Daily treatment consisted of UFT (300 to 400 mg/body) and CPA (100 to 150 mg/body), both given orally. RESULTS: The treatment period ranged from 4 to 80 weeks. The response rate was 35%, while it was 65% in the "stable disease > 6 months" category. The mean time to the first sign of response was 7 weeks and the time to tumor progression was 37 weeks. The frequent adverse effects were leukocytopenia (55%) and gastrointestinal symptoms (35%). The incidence of adverse grade > or = 3 effects was 25%. CONCLUSION: Oral UFT and CPA combination chemotherapy may be suitable for MBC.
Adult↗