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Biomedical subjects

I Sekine

Publications and source records attributed to I Sekine.

At least 91 records · Page 5Linked to original sources
PubMed1998

Histopathological study of the use of freeze-dried allogenic dentin powder and True Bone Ceramic as apical barrier materials.

The biocompatibility of freeze-dried allogenic dentin powder and True Bone Ceramics (TBC), the latter prepared by incineration of bovine bone, as apical barrier materials was evaluated histopathologically in dogs. After pulpectomy, 80 root canals of 53 dog premolar teeth were prepared, and each material was tightly packed to the apical stop area. The remainder of the canal was filled with guttapercha by the lateral condensation method. Control teeth were filled by the lateral condensation method using gutta-percha without constructing apical barriers. In both the teeth filled with the dentin powder and those filled with TBC, multinucleate giant cells appeared on the bone resorption surface and the surface of the root canal wall, and marked bone resorption and positive tartrate-resistant acid phosphate staining were observed. Hard tissue had formed on the root canal wall and the filling material after 3 months. These findings suggest that the test materials are nonirritative and compatible with periapical tissue, and that they may be useful and clinically applicable as apical barrier materials.

Animals↗
PubMed1998

Mutational analysis of the N-ras gene in acute lymphoblastic leukemia: a study of 125 Japanese pediatric cases.

A point mutation of the N-ras gene is one of the known genetic alterations identified in patients with acute lymphoblastic leukemia (ALL), but its clinical importance is still controversial. Using polymerase chain reactions, we examined codons 12, 13 and 61 of this gene in 125 Japanese childhood ALL patients (64 common-ALL, 22 pre-B-ALL, 33 T-ALL, 2 B-ALL, 3 undifferentiated ALL, and 1 unclassified ALL) including 9 relapsed patients. An N-ras point mutation was observed in 14 (11%) patients (9 common-ALL, 3 T-ALL, and 2 undifferentiated ALL; 13 patients at diagnosis and 1 at relapse). The patients with undifferentiated ALL harbored an N-ras mutation at a significantly higher rate. However, no correlation was found between the presence of an N-ras mutation and sex, age, or white blood count. There was no significant difference in the event-free survival rate between 13 fresh patients with an N-ras mutation and 103 patients with a wild-type configuration. The N-ras mutation was present in about 10% of childhood ALL cases but it did not have a prognostic impact. The sequence analyses revealed that the majority of the patients (13/14) had an N-ras mutation of a G to A transition. This finding was consistent with previous reports on N-ras mutations in acute leukemias in which the incidence of a G to A mutation was significantly higher in ALL than in myeloid malignancies.

Child↗
PubMed1998

Response rate as an endpoint for evaluating new cytotoxic agents in phase II trials of non-small-cell lung cancer.

BACKGROUND: Response rate (RR) has been used as a defining endpoint of new-agent phase II trials for non-small-cell lung cancer (NSCLC). However, tumor responses to chemotherapy do not always result in prolonged survival of patients with this disease. DESIGN: Single-agent phase II trials were identified by a MEDLINE search of the period from 1976 to 1995. Associations between RR, median survival time (MST) and characteristics of patients who entered the trial, including tumor extent, performance status and prior chemotherapy, were studied by using the logistic regression model. RESULTS: A total of 183 treatment arms in 176 trials (including 10 randomized phase II trials) were identified. The overall RR in the 6768 evaluable patients was 11%. Eleven drugs, cisplatin, epirubicin, ifosfamide, edatrexate, irinotecan, vinorelbine, docetaxel, paclitaxel, etoposide, vindesine, and 254-S, produced a RR of more than 20%. An MST of eight months or longer was obtained with 12 drugs, but there were cases in which no objective responses were produced by these drugs. MST was correlated with RR (r = 0.504, P < 0.0001), but ranged broadly at a given level of RR. Multiple linear regression analysis showed a significant correlation between RR and MST (regression coefficient = 0.60, P = 0.00003) after adjustment for other variables. CONCLUSIONS: RR was significantly correlated with MST in single-agent phase II trials for NSCLC, but there is room for further consideration of the endpoint of these trials.

Antineoplastic Agents↗
PubMed1998

Significance of angiogenic factors in liver metastatic tumors originating from colorectal cancers.

We examined the expression of vascular endothelial growth factor (VEGF) and microvessel counts expressed by CD34 staining in 39 patients with primary and 44 patients with metastatic liver tumors of metastatic colorectal carcinoma, and 29 patients with nonmetastatic colorectal carcinoma as control in order to determine their value in the evaluation of prognosis and recurrence after hepatectomy. Microvessel counts in primary colorectal carcinomas of the metastatic group were significantly higher than those in control (P<0.05). Neither factor correlated with any clinicopathological feature of primary or metastatic liver carcinomas. Higher microvessel counts in metastatic liver tumors tended to be associated with a shorter disease-free interval to second recurrence in the remaining liver (P = 0.069) and were significantly associated with poor prognosis after hepatectomy (P<0.05). We conclude that microvessel count is an important marker of liver metastasis and prognosis in patients with colorectal carcinoma treated with hepatectomy.

Adult↗
PubMed1998

Microsatellite instability in female non-small-cell lung cancer patients with familial clustering of malignancy.

There is accumulating evidence of an increased risk of familial clustering of cancer in the first-degree relatives of lung cancer probands. However, no explanation has been proposed for these epidemiological data. We reviewed 379 female non-small-cell lung cancer (NSCLC) patients to obtain their family histories of malignancy. Among them, nine female NSCLC patients with three or more relatives diagnosed with malignancy and 28 control patients without a family history of malignancy were selected to be analysed for instability at six different microsatellite loci. We observed microsatellite instability (MSI) more frequently in the patients with three or more family histories of malignancy (six out of nine, 67%) than the control patients (5 out of 28, 18%). The incidence of MSI in the former was significantly higher than that in the control (P=0.011: Fisher's exact test). We detected no significant difference in clinicopathological characteristics between the cases with MSI and those without MSI, except for their family histories of cancer. Our results show that a significantly higher rate of MSI is associated with familial clustering of malignancy. MSI could be one of the underlying mechanisms for familial clustering of malignancy in female NSCLC patients.

Adenocarcinoma↗
PubMed1998

Inducible nitric oxide synthase is expressed in granuloma pyogenicum.

It is known that granuloma pyogenicum (GP) grows rapidly but cherry angioma (CA) does not, although they show the same histological features of hyperplasia of the capillary vessels. Although some cytokines have been thought to be angiogenic factors, a nitric oxide (NO) synthase-dependent effector mechanism is reported to be involved in macrophage-derived angiogenesis in humans. Under the hypothesis that this mechanism is also involved in the more rapid growth of GP, we examined the expression of inducible NO synthase (iNOS) in GP as compared with that in CA. The expression of iNOS mRNA was detected in GP, but not in CA, by reverse transcription-polymerase chain reaction (RT-PCR) analysis. In situ hybridization (ISH) demonstrated iNOS mRNA expression in endothelial cells and to a lesser extent round cells and spindle cells in the myxomatous stroma in GP. Immunohistochemical study showed that iNOS protein was expressed in endothelial cells, infiltrating round cells and spindle cells in the stroma in GP. These results suggested that a NOS-dependent mechanism may be involved in angiogenesis and the rapid growth of GP.

Adult↗
PubMed1998

Inhibition of IL-12 synthesis of peripheral blood mononuclear cells (PBMC) stimulated with a bacterial superantigen by pooled human immunoglobulin: implications for its effect on Kawasaki disease (KD).

The aim of this study was to further assess the role of pooled human immunoglobulin (PHIG) on cytokine production from PBMC stimulated with a bacterial superantigen. Human PBMC were cultured with Streptococcus pyrogenic exotoxin A (SPE-A) with or without PHIG and several proinflammatory cytokine levels of culture supernatants were measured. Serum cytokine levels of KD patients before and after PHIG therapy were also examined. PHIG greatly reduced the production of IL-12, interferon-gamma (IFN-gamma) and other cytokines from SPE-A-stimulated PBMC, while exogenous IL-12, but neither IL-1 nor tumour necrosis factor-alpha (TNF-alpha), restored IFN-gamma production inhibited by PHIG. Although PHIG partially adsorbed SPE-A, its inhibitory effect on cytokine production was not played by anti-SPE-A antibody. Although purified CD4+ T cells cultured with human HLA-DR-transfected mouse L cells and SPE-A could not effectively produce IFN-gamma, they produced large amounts of IFN-gamma if exogenous IL-12 was introduced. KD patients in the acute phase had higher levels of serum IFN-gamma than did controls and patients with bacterial infection. Although IL-12 levels of children with or without KD were not significantly different, IL-12 levels of children were much higher than those of adults. However, serum levels of IL-12 of KD patients were transiently but significantly decreased by PHIG therapy and IFN-gamma amounts subsequently reverted to basal levels thereafter. These findings indicate that PHIG inhibits IL-12 production of SPE-A-activated monocytes and thereby decreases IFN-gamma synthesis by T cells and suggest that inhibition of IL-12 and IFN-gamma production is an important part of the mechanisms underlying PHIG therapy on KD.

Adsorption↗
PubMed1998

Recurrence of a germ cell tumor 12 years after initial treatment: a case report.

Patients with testicular germ cell tumors who have disease-free remission for more than 2 years are usually considered to be cured of their disease. This report describes a case of a germ cell tumor recurring 12 years after initial diagnosis and its treatment in a 35-year-old man who developed a retroperitoneal mass adhering to the abdominal aorta with a bout of severe colic in the left flank. Although tumor markers were not elevated and histology of the biopsy specimen was initially diagnosed as adenocarcinoma, we finally concluded that the retroperitoneal tumor was teratoma developing as a recurrence of the germ cell tumor for the following reasons: (1) the histology of the specimen was similar to an epithelial component of teratoma found in the tissue resected 12 years before; (2) systemic survey failed to detect any other primary site; (3) the young age of this patient was consistent with germ cell tumor rather than adenocarcinoma; and (4) the retroperitoneum is the most frequent site of late recurrences of testicular cancer. He was treated successfully with combination chemotherapy of cisplatin, etoposide and bleomycin followed by surgery. It is important to differentiate this treatable disease from metastasis from an unknown primary, because the latter responds poorly to therapy and survival is usually short.

Adult↗
PubMed1998

Factors that influence the eligibility of cases for inclusion in clinical trials. The Lung Cancer Chemotherapy Study Group of the Japan Clinical Oncology Group.

BACKGROUND: It is important to minimize the incidence of ineligible cases to improve the quality of clinical trials. To determine factors which may influence the incidence of ineligible cases, the incidence of and reasons for ineligibility in clinical trials were retrospectively analyzed. METHODS: We retrospectively examined the incidence of and reasons for ineligibility for inclusion in eight clinical trials conducted by the Lung Cancer Chemotherapy Study Group of the Japan Clinical Oncology Group and four trials financed by trust funds from a pharmaceutical company. RESULTS: In these 12 clinical studies, the incidence of ineligibility was 4.2% (32/762) (range 0-10.6%). Specific factors that might influence the incidence of ineligible cases were then analyzed. There was a significant difference in the incidence of ineligibility between the methods of registration (P < 0.05). The incidences using a central registration and without using a central registration system were 2.8% (9/322) and 5.2% (23/440) respectively. We also analyzed ineligible cases in clinical studies published in the Journal of Clinical Oncology. In clinical studies published in the Journal of Clinical Oncology recently and 10 years ago, the incidences of ineligible cases were 5.0% (942/18 878) and 4.1% (206/4995) respectively. In clinical studies on lung cancer published in the Journal of Clinical Oncology from 1984 to 1995, the incidence of ineligible cases was 4.7% (900/19,116). There was no significant difference in the incidence of ineligible cases between our 12 studies and the Journal of Clinical Oncology clinical studies by the chi 2 test (P > 0.05). CONCLUSIONS: We conclude that the incidence of ineligible cases in our studies is similar to that in clinical trials published in the Journal of Clinical Oncology. Central registration systems are useful for checking for ineligibility, and to increase the quality of clinical trials.

Clinical Trials as Topic↗
PubMed1998

Cancer chemotherapy in the elderly.

As the geriatric population is growing, it is increasingly important to be familiar with chemotherapy for the elderly. Age-related changes in pharmacokinetics are documented for doxorubicin, etoposide, ifosfamide, daunorubicin, mitomycin, cisplatin and methotrexate. The hematological toxicity of most standard-dose chemotherapy is not affected by age in patients with normal organic functions and good performance status, although increased toxicity with aging is suggested in the use of actinomycin-D, etoposide, vinblastin, methotrexate, methyl-CCNU, doxorubicin and mitomycin, and in dose-intensive chemotherapy. Among non-hematological toxicities, only doxorubicin-induced cardiomyopathy and bleomycin-induced pulmonary toxicity are demonstrated to be accelerated in the elderly. There is no evidence that advanced age decreases the efficacy of chemotherapy for tumors, except for Hodgkin's disease and acute leukemia. These results suggest that advanced chronological age alone is not always associated with severe toxicity and poor prognosis, and that many elderly patients with cancer will benefit from chemotherapy. To answer questions regarding the optimal chemotherapy regimen, dose and intensity in this population, the influence of age should be analyzed in a multivariate approach in future studies.

Adolescent↗
PubMed1998

Immunohistochemical study of p53 overexpression in radiation-induced colon cancers.

The expressions of p53 and proliferating cell nuclear antigen (PCNA) were studied immunohistochemically from paraffin sections of 7 cases (9 lesions) of radiation-induced colon cancer and 42 cases of spontaneous colon cancer. Age distribution of radiation-induced and spontaneous colon cancer were 68.1 years (range, 56 to 77 years) and 67.4 years (range, 31 to 85 years), respectively. Among the radiation-induced colon cancers, there were 3 lesions of mucinous carcinoma (33%), a much higher than found for spontaneous mucinous cancer. Immunohistochemically, p53 protein expression was detected in 7/9 (78%) of radiation-induced cancers and in 23/42 (55%) of spontaneous colon cancers. chi 2 analysis found no significant differences between radiation-induced and spontaneous colon cancers in age distribution or p53-positive staining for frequency, histopathology, or Dukes' classification. In radiation colitis around the cancers including aberrant crypts, spotted p53 staining and abnormal and scattered PCNA-positive staining were observed. In histologically normal cells, p53 staining was almost absent and PCNA-positive staining was regularly observed in the lower half of the crypt. In radiation colitis including aberrant glands, cellular proliferation increased and spotted p53 expression was observed. This study suggests that radiation colitis and aberrant glands might possess malignant potential and deeply associate with carcinogenesis of radiation-induced colon cancer.

Adult↗
PubMed1998

Childhood thyroid cancer: comparison of Japan and Belarus.

The high incidence of childhood thyroid cancer in Belarus is suspected to be due to radiation exposure after the Chernobyl reactor accident. To clarify the clinical and histological characteristics of childhood thyroid cancer in Belarus, we therefore compared these patients to a radiation non-exposed control series in Japan. In Belarus, 26 thyroid cancers in subjects aged 15 or younger were diagnosed among 25,000 screened between 1991 and 1995 by Chernobyl-Sasakawa Health and Medical Cooperation Project. The clinical and morphologic features of these 26 cases were compared to 37 childhood thyroid cancers in Japan diagnosed between 1962 and 1995. The age distribution at operation in Belarus showed a peak at 10 years old, with a subsequent fall in numbers. In contrast, the age distribution at operation in Japan showed a smooth increase between the ages of 8 and 14. The mean tumor diameter was smaller in Belarus than that in Japan (1.4 +/- 0.7 vs. 4.1 +/- 1.7 cm, P < 0.001). The sex ratio, regional lymph node metastasis, extension to surrounding tissues or lung metastasis did not differ significantly. Histologically, all cases in Belarus were papillary and in Japan 33 cases were papillary and 4 cases were follicular carcinomas. Among papillary carcinomas, the frequency of a solid growth pattern, a criteria for classifying a tumor as poorly differentiated, was higher in Belarus than that in Japan (61.5 vs. 18.2%, P < 0.001). The difference between the features of childhood thyroid cancer in Japan and Belarus may be due to the difference in the process of carcinogenesis, but more direct evidence and further analysis by molecular epidemiology are needed in Belarussian cases.

Adenocarcinoma, Follicular↗
PubMed1998

Mediastinal germ cell tumor complicated by visceral hemangiomatosis.

This report describes an extremely rare combination of mediastinal germ cell tumor and visceral hemangiomatosis in a 17-year-old boy who initially presented with chest pain and dyspnea. He was treated with chemotherapy consisting of cisplatin, cyclophosphamide, bleomycin, vinblastine, and dactinomycin followed by surgery. Multiple low-density nodules developed in the spleen three weeks later, suggesting metastases from the primary tumor, but the resected specimen showed cavernous hemangiomas within the splenic parenchyma. The patient died of recurrence of germ cell tumor 19 months after the initial treatment. Postmortem examination disclosed multiple hemangiomas in the lung and liver similar to those in the spleen.

Adolescent↗
PubMed1998

Expression of the ets-1 proto-oncogene in human pancreatic carcinoma.

The proto-oncogene, ets-1, is a transcription factor that controls the expression of a number of genes involved in extracellular matrix remodeling. It might play a role in cell migration and tumor invasion. To elucidate the involvement of Ets-1 in human pancreatic carcinoma, we performed immunohistochemical analysis on tissue from 10 normal pancreases and 103 cases of pancreatic carcinoma. We compared the degree of Ets-1 expression. In addition, among the pancreatic carcinomas, we compared Ets-1 expression in relation to the differentiation, lymph node metastasis and the depth of invasion of the carcinoma. Ets-1 was expressed faintly in normal pancreatic tissue. Among the 103 cases of pancreatic carcinoma, 83 (80.5%) showed positive staining for the Ets-1 protein. Histologically, papillary carcinoma, well-differentiated adenocarcinoma, and moderately differentiated adenocarcinoma expressed high positivity for Ets-1. In contrast, poorly differentiated adenocarcinoma expressed relatively weak positivity for Ets-1. Ets-1 expression had no relation to the presence of lymph node metastasis, tumor size, prognosis, or tumor-node-metastasis stage in pancreatic carcinomas. In situ hybridization also confirmed the presence of ets-1 mRNA in pancreatic carcinomas. We detected expression of ets-1 mRNA in three human pancreatic carcinoma cell lines by the reverse transcription-polymerase chain reaction method. These findings suggest that Ets-1 expression is related to the carcinogenesis of human pancreatic carcinoma, but its relationship to tumor progression is unclear.

Adult↗
PubMed1998

[Paclitaxel (taxol): a review of its antitumor activity and toxicity in clinical studies].

Paclitaxel (Taxol) is a new class of anti-tumor agents which act by promoting the assembly and inhibiting the disassembly of microtubules. Single-agent studies have shown its significant activity for advanced cancers in various organs including ovary, lung, breast, and head and neck. Combination therapies with other anticancer agents have been extensively investigated in these cancers. Paclitaxel combined with cisplatin is now considered to be the standard treatment for advanced ovarian cancer. In other cancers, promising results have been obtained in several studies of paclitaxel-based chemotherapy. Major toxicities of paclitaxel-monotherapy are hypersensitivity reaction, neutropenia, and peripheral neuropathy. Combination of other cytotoxic agents sometimes leads to severer toxicities such as neurotoxicity with cisplatin and cardiotoxicity with anthracycline. Although further evaluation is needed, paclitaxel will be a main agent in the treatment of advanced solid tumors.

Antineoplastic Agents, Phytogenic↗
PubMed1998

[Treatment of children with non-Hodgkin's lymphoma with CCLSG NHL 855/890 protocols long-term outcome and incidence of secondary malignancies].

We report here on treatment results of consecutive CCLSG NHL studies (NHL855, 1985-1989; NHL890, 1989-1996). The NHL855 protocol consisted of an induction phase of five drugs (VCR, PRD, CPM, DXR, and high-dose MTX) and a maintenance phase of 7 drugs. The probabilities of EFS at 7 years were 78% (SE, 10%) for the patients with localized disease, and 38% (SE, 7%) for those with advanced disease. In the NHL 890 protocol, the patients were assigned to two different treatment groups according to their histology and received different consolidation therapy; non-lymphoblastic subtype was treated almost identically to NHL855 while LASP and VP-16 were newly added for the lymphoblastic subtype. The 7-year EFS improved to 91% (SE, 6%) for localized disease, and 61% (SE, 6%) for advanced disease. A remarkable improvement was particularly evident for lymphoblastic type with mediastinal mass. Optional trial of high-dose sequential chemotherapy and peripheral blood progenitor cell auto grafting resulted in an unfavorable outcome. The 7-year EFS according to main histological subgroups were as follows: 84% (10%) for large cell type, 67% (11%) for Burkitt's-type, 58% (10%) for lymphoblastic type. Secondary cancer occurred in two of the 163 patients studied. Both patients were AML (M0/M4) and MLL rearrangement was detected in the M4 case.

Adolescent↗
PubMed1998

[Bone marrow relapse in high-risk pediatric patients with acute lymphoblastic leukemia: a comparison of relapse times and initial clinical features of patients on different protocols. Children's Cancer and Leukemia Study group (CCLSG)].

To clarify the efficacy of modern intensive chemotherapy for ALL patients with unfavorable features, we compared the time to failure and initial clinical features of children who relapsed in the bone marrow or combined sites, as documented by early CCLSG studies (H811 and H851; 1981-1987) and later studies (H874 and H/HH911; 1987-1993) concerning high-risk ALL patients. In the later studies patients outcomes with new intensive regimens employing early intensification and reinduction therapy were apparently better than those of patients in the early studies with conventional regimens. When we compared the number of relapsed patients based on duration of first remission, we found that the improved outcomes for patients in the later studies were due to a decrease in the number who relapsed 7-36 months after the start of treatment (intermediate relapse), and that the percentage of those who relapsed within the first 6 months of therapy (early relapse) was higher. Patients with high initial WBC counts tended to relapse much earlier than those with low initial WBC counts. However, in the later studies, patients with high WBC counts often relapsed after the termination of therapy (late relapse). These results suggest that the intensive chemotherapy regimens used in the later studies can prevent the development of drug resistant leukemic clones, except in extremely high-risk patients likely to relapse within the first 6 months of therapy.

Antineoplastic Combined Chemotherapy Protocols↗