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Biomedical subjects

I Sekine

Publications and source records attributed to I Sekine.

At least 19 recordsLinked to original sources
PubMed2005

Overexpression of Ets-1 proto-oncogene in latent and clinical prostatic carcinomas.

AIMS: The high incidence of clinically diagnosed prostatic cancer is exceeded by the frequency of tumours detected at autopsy. The Ets-1 proto-oncogene is expressed by a variety of malignant and normal tissues. Therefore, in this study, expression of Ets-1 protein was investigated in 'latent' prostatic cancer detected at autopsy, compared with benign prostatic hyperplasia, normal prostatic tissues and clinical prostatic cancer. METHODS AND RESULTS: Using immunohistochemistry, we analysed Ets-1 expression in 95 prostatic specimens including 19 cases of latent prostatic carcinoma (LPC) and 55 cases of clinical prostatic carcinoma (CPC), 11 cases of benign prostatic hyperplasia (BPH) and 10 cases of normal prostate (NP). Differences in the incidence of LPC and CPC suggest different courses for the biological progression of prostatic cancer. There was a significant difference in the degree of Ets-1 expression in CPC and LPC (P < 0.05). Ets-1 was not expressed in BPH and NP, but in malignant cases (57 of 74; 77.0%) commonly demonstrated immunoreactivity in the tumour cells. In our study the expression of Ets-1 between benign and malignant, and well, moderately and poorly differentiated adenocarcinomas of prostatic cancer showed significant differences. The presence of Ets-1 mRNA was confirmed by in-situ hybridization in human prostatic tissues. CONCLUSION: Our results suggest that Ets-1 might play an important role in carcinogenesis and/or the progression of human prostatic carcinomas.

Humans↗
PubMed2005

Cyclin D1 overexpression in thyroid papillary microcarcinoma: its association with tumour size and aberrant beta-catenin expression.

AIMS: Cyclin D1 is a target molecule transcriptionally activated by aberrant beta-catenin in Wnt signalling. Thyroid papillary microcarcinoma (PMC) may be considered a precursor of papillary thyroid cancer (PTC). Ki67 is widely used as a proliferation marker. The aim of this study was to determine whether cyclin D1 overexpression is involved in early thyroid carcinogenesis. METHODS AND RESULTS: Thirty-five cases of PMC were examined immunohistochemically, including 11 cases less than 5 mm (PMC < 5) and 24 cases more than 5 mm (PMC > 5), and 18 PTC cases (size 11-15 mm). Cyclin D1 expression was significantly lower in PMC < 5 than in PMC > 5, while there was no significant difference between PMC > 5 and PTC. Statistical analysis revealed significant correlations between cyclin D1 labelling index (LI) and Ki67 LI (P = 0.0272)/cytoplasmic beta-catenin expression (P < 0.001) in PMC and PTC. Four of five PMC > 5 cases with lymph node (LN) metastases displayed a high cyclin D1 LI and strong cytoplasmic beta-catenin expression. CONCLUSIONS: Cyclin D1 overexpression and correlation with aberrant beta-catenin expression were demonstrated in PMC. Cyclin D1 expression was significantly associated with tumour size and LN metastases in PMC. Cyclin D1 may be up-regulated at an early stage of thyroid carcinogenesis and promote tumour growth and metastatic potency in PMC through activation of the Wnt/beta-catenin pathway.

Adult↗
PubMed2005

Expression of p-STAT3 in human colorectal adenocarcinoma and adenoma; correlation with clinicopathological factors.

BACKGROUND: The signal transducer and activator of transcription 3 (STAT3) is a key signalling molecule implicated in the regulation of growth and malignant transformation. Constitutive activation of STAT3 is seen in several tumour derived cell lines, and in a wide variety of human malignancies. AIMS: To examine the relation between p-STAT3 (activated form of STAT3) expression and clinicopathological factors in human colorectal adenocarcinoma and adenoma. METHODS: Immunohistochemical analyses were carried out on tissues from 44 colorectal adenomas and 95 colorectal adenocarcinomas, comprising 18 intramucosal carcinomas and 77 invasive carcinomas. RESULTS: Seventy seven of these 139 samples (55.4%) showed immunoreactivity for p-STAT3. Positive staining for p-STAT3 was seen in 69 of the 95 carcinomas. Only eight of the 44 adenomas showed immunopositivity for p-STAT3, resulting in a significant difference between total adenocarcinomas and adenomas (p < 0.001). Among the 95 cases of colorectal adenocarcinoma, p-STAT3 immunoreactivity was significantly correlated with the depth of tumour invasion (p < 0.05), venous invasion (p < 0.05), lymph node metastasis (p < 0.05), and increasing stages of the Dukes' classification (p < 0.01). Expression of p-STAT3 was detected by Western blot analysis in two different cultured human colorectal carcinoma cell lines and six colon carcinoma tissue samples obtained at surgery. CONCLUSION: This is the first study to report a significant correlation of p-STAT3 expression with the depth of tumour invasion. These findings suggest that p-STAT3 expression is an important factor related to carcinogenesis and/or tumour invasion of colorectal adenocarcinoma.

Adenocarcinoma↗
PubMed2005

Expression of the ets-1 proto-oncogene in human breast carcinoma: differential expression with histological grading and growth pattern.

The proto-oncogene, ets-1, is a transcription factor known to control the expression of a number of genes and has been postulated to play a role in cell growth, differentiation and tumour invasion. We examined 137 cases of breast carcinoma by immunohistochemistry and compared the degree of Ets-1 expression among the different histological types of invasive carcinomas. Ets-1 was not expressed in the normal breast epithelium nor in noninvasive carcinomas. Among the 137 breast carcinoma cases, 104 (83.2%) showed positive staining for the Ets-1 protein. Histologically, invasive ductal carcinomas expressed immunopositivity with intense staining for Ets-1 in the tumour cells. Ets-1 expression correlated with Bloom-Richardson grading in invasive ductal carcinoma (p<0.01). However, there was no correlation between Ets-1 expression and lymph node metastasis, "t" classification or TNM staging. In situ hybridization confirmed the presence of Ets-1 mRNA in breast carcinomas. The expression of Ets-1 mRNA was detected in two of three different kinds of cultured human breast carcinoma cell lines and one of three human breast carcinoma tissues by the reverse transcription polymerase chain reaction method. These findings suggest that ets-1 is overexpressed in ductal cells of the breast that have undergone malignant conversion and that ets-1 is one of the factors associated with tumour growth and histological differentiation of breast carcinomas.

Breast↗
PubMed2004

Multi-institutional phase II trial of irinotecan, cisplatin, and etoposide for sensitive relapsed small-cell lung cancer.

Irinotecan (CPT-11) has been shown to exhibit excellent antitumour activity against small-cell lung cancer (SCLC). A multi-institutional phase II study was therefore conducted to evaluate the efficacy and toxicity of CPT-11 combined with cisplatin (CDDP) and etoposide (ETOP) (PEI regimen) for the treatment of sensitive relapsed SCLC. Patients who responded to first-line chemotherapy but relapsed more than 8 weeks after the completion of first-line therapy (n=40) were treated using the PEI regimen, which consisted of CDDP (25 mg m(-2)) weekly for 9 weeks, ETOP (60 mg m(-2)) for 3 days on weeks 1, 3, 5, 7, and 9, and CPT-11 (90 mg m(-2)) on weeks 2, 4, 6, and 8 with granulocyte colony-stimulating factor support. Five complete responses and 26 partial responses were observed, and the overall response rate was 78% (95% confidence interval 61.5-89.2%). The median survival time was 11.8 months, and the estimated 1-year survival rate was 49%. Grade 3/4 leucocytopenia, neutropenia, and thrombocytopenia were observed in 55, 73, and 33% of the patients, respectively. Nonhaematological toxicities were mild and transient in all patients. In conclusion, the PEI regimen is considered to be highly active and well tolerated for the treatment of sensitive relapsed SCLC.

Adult↗
PubMed2004

Expressions of parathyroid hormone-related protein (PTHrP) and PTH/PTHrP-receptor (PTH/PTHrP-R) in gastrointestinal stromal tumours (GISTs), leiomyomas and schwannomas.

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are rare, c-kit and CD34 positive, and different from other mesenchymal tumours of the gastrointestinal tract (e.g. leiomyomas and schwannomas). The purpose of this study was to investigate the roles of parathyroid hormone-related protein (PTHrP) and parathyroid hormone/parathyroid hormone-related protein-receptor (PTH/PTHrP-R) in the growth and differentiation of GISTs. METHODS: Nineteen GISTs, six leiomyomas and five schwannomas were examined in this study. RESULTS: All of the GISTs and leiomyomas, and four of the schwannomas (80.0%) were positive for PTHrP. Immunohistochemical staining revealed that all of the leiomyomas, 90% of the GISTs and 80% of the schwannomas expressed PTH/PTHrP-R. Furthermore, both PTHrP and PTH/ PTHrP-R were expressed in the cytoplasm of identical cells in all of these tumours. CONCLUSION: Our results suggest that both PTHrP and PTH/PTHrP-R play an important role in the growth and differentiation of GISTs, leiomyomas and schwannomas.

Gastrointestinal Neoplasms↗
PubMed2004

Expression of Tie-1 and 2 receptors, and angiopoietin-1, 2 and 4 in gastric carcinoma; immunohistochemical analyses and correlation with clinicopathological factors.

AIMS: There is strong evidence that tyrosine kinases are involved in the regulation of tumour progression, cellular growth and differentiation. Recently, many kinds of tyrosine kinase receptors have been reported, and among them Tie-1 and 2 constitute a major class. Angiopoietin (Ang)-1 is known as a ligand of the Tie-2 tyrosine kinase receptor. The aim of this study was to determine the expression profile of Tie-1 and 2 and Ang-1, 2 and 4 in gastric adenocarcinoma. METHODS AND RESULTS: Eighty-nine cases of surgically resected human gastric adenocarcinoma were studied by immunohistochemistry. Of these, 60 (67.4%), 61 (68.5%), 69 (77.5%), 75 (84.3%), and 47 cases (52.8%) showed positive staining in the cytoplasm of carcinoma cells for the Tie-1 and 2 and Ang-1, 2 and 4 proteins, respectively. The expression of Ties and Angs was significantly correlated with several type of histological differentiation and several clinicopathological factors. CONCLUSIONS: Ties and Angs were highly expressed in human gastric adenocarcinoma cells. These findings suggest that the Tie-Ang receptor-ligand complex is one of the factors involved in the cellular differentiation and progression of human gastric adenocarcinoma.

Adenocarcinoma↗
PubMed2003

Phase I/II trial of weekly cisplatin, etoposide, and irinotecan chemotherapy for metastatic lung cancer: JCOG 9507.

Combinations of cisplatin-irinotecan and cisplatin-etoposide are active and well tolerated in patients with both small-cell lung cancer (SCLC) and nonsmall-cell lung cancer (NSCLC). To define the recommended dose for phase II trials of irinotecan combined with cisplatin and etoposide in chemonaive patients with stage IV disease, 56 patients (11 having SCLC and 45 NSCLC) received cisplatin 25 mg m(-2) weekly for 9 weeks, etoposide 60 mg m(-2) for 3 days on weeks 1, 3, 5, 7 and 9, and irinotecan 20-100 mg m(-2) (levels 1-8) on weeks 2, 4, 6 and 8, together with a prophylactical granulocyte colony-stimulating factor support (50 microg m(-2) on days 4-7 on weeks 1, 3, 5, 7 and 9, and on days 2-7 on weeks 2, 4, 6 and 8). Grade 3-4 leukocytopenia, neutropenia and thrombocytopenia were noted in 20 (36%), 28 (50%) and nine (16%) patients, respectively. Grade 3 diarrhoea, grade 3 cardiac toxicity, and grade 4 transaminase elevation developed in one (1.8%) patient each. Totally, four of 56 patients were removed from the study because of toxicity and recovered, and two other patients died in situations where drug toxicity might contribute to their death. Dose-limiting toxicity was noted in less than one-third of patients at dose levels 1-7, but in all patients at dose level 8. Thus, the recommended dose was determined to be level 7 (irinotecan 90 mg m(-2)). The response rates for SCLC and NSCLC were 91% (10/11) and 38% (17/45), respectively. The median survival time and 1-year survival rate were 11.9 months and 46% for SCLC and 10.1 months and 40% for NSCLC, respectively. This regimen was considered to be feasible and promising for the treatment of stage IV SCLC and NSCLC.

Adult↗
PubMed2003

Cryptic insertion and translocation or nondividing leukemic cells disclosed by FISH analysis in infant acute leukemia with discrepant molecular and cytogenetic findings.

Of 51 infants with acute leukemia, 13 (25%) had contradictory findings on 11q23/MLL rearrangements that were analyzed by cytogenetic and Southern blot methods: seven had rearranged MLL and normal karyotype, four had rearranged MLL and abnormal karyotype with no 11q23 translocation, and two had germline MLL and 11q23 translocations. Fluorescent in situ hybridization (FISH) analysis using an MLL probe that was performed to elucidate the discrepancy disclosed the presence of normal dividing cells and nondividing leukemic cells in the same bone marrow in five patients, and cryptic insertion or translocation in another five. Subsequent FISH and reverse transcription-polymerase chain reaction analysis identified the MLL-AF10, MLL-AF4, or MLL-AF1q fusions that were produced by the cryptic rearrangements in four of the five patients. In the remaining three patients, the breakpoint of 11q23 translocation was located distal to the MLL locus in one, and the discrepancy was unresolved in two. Thus, FISH should complement cytogenetic analysis when cytogenetic and molecular genetic findings are contradictory in infant leukemia, and when infant leukemia does not show 11q23 translocations or other specific translocations including t(7;12), t(1;22), etc that are recurrently found in infant leukemia.

Blotting, Southern↗
PubMed2003

Circulating endothelial cells in Kawasaki disease.

Recent reports have demonstrated that circulating endothelial cells (CECs) are observed in several diseases with vascular injury. Because Kawasaki disease (KD) is one type of systemic vasculitis, we hypothesized that an increased number of CECs may be associated with the appearance of complicated coronary artery lesions (CAL). In the present study we investigated the enumeration and origin of CECs in 20 patients with KD, using an immunohistochemical method with monoclonal antibodies: clone P1H12 against ECs and clone AC133 against endothelial progenitor cells (EPCs), which were derived from the bone marrow. The mean number of CECs increased significantly (P < 0.05) from the acute through the subacute phases of KD compared with both the convalescent phase of KD and healthy children. The mean number of CECs was significantly (P < 0.05) higher in six KD patients with CAL than in 14 KD patients without CAL. The population of EPCs in the total CECs in KD was 4.4 +/- 1.2% (range 0-18%). The number of EPCs during the subacute phase was also significantly higher (P < 0.05) in KD patients with CAL than in those without CAL. Our findings indicate that the number of CECs increase in KD vasculitis and suggest that the increased numbers of CECs and EPCs may reflect the EC damage of this disease.

Acute Disease↗
PubMed2003

Distant failure after treatment of postoperative locoregional recurrence of non-small cell lung cancer.

BACKGROUND: The standard treatment for patients with locoregional recurrence of non-small cell lung cancer (NSCLC) after complete resection has not been established. The aim of this study was to evaluate clinicopathologic characteristics, type of locoregional recurrence, pattern of subsequent failure, and survival after the recurrence. METHODS: Of 743 patients undergoing pulmonary resection for NSCLC in the National Cancer Center Hospital between 1990 and 1995, we retrospectively reviewed the medical charts of the 43 patients (5.8 %) found to have locoregional recurrence without distant metastasis or pleural or pericardial involvement. RESULTS: The median time to locoregional recurrence was 13.6 months (range: 1.6 - 85.8 months). The most frequent site of recurrence was the mediastinal nodes in 21 of 43 patients (49 %). 33 patients (77 %) received further treatment for the recurrence: thoracic irradiation in 26, surgery in two, systemic chemotherapy in two, and a combination of the above in 3 patients. Subsequent distant failure was detected in 26 (68 %) of the 38 patients assessable for the analysis of failure pattern: lung in 11, brain in 6, bone in 5, and others in 13. The median interval from the recurrence to distant failure was 8.4 months (range: 1.7-56.4 months). The median survival time after diagnosis of the locoregional recurrence was 10.5 months (range: 0-74.0 months). A multivariate analysis showed that local therapy for the locoregional recurrence had no significant impact on postrecurrent survival or distant failure-free survival. CONCLUSIONS: Many patients with postoperative locoregional recurrence developed distant metastases early after the first recurrence. Systemic chemotherapy in addition to local therapy may be of benefit in this population.

Adult↗
PubMed2003

Randomized phase II study of cisplatin, irinotecan and etoposide combinations administered weekly or every 4 weeks for extensive small-cell lung cancer (JCOG9902-DI).

BACKGROUND: The purpose of this study was to evaluate the toxicity and antitumor effect of cisplatin, irinotecan and etoposide combinations on two schedules, arms A and B, for previously untreated extensive small-cell lung cancer (E-SCLC), and to select the right arm for phase III trials. PATIENTS AND METHODS: Sixty patients were randomized to receive either arm A (cisplatin 25 mg/m(2) day 1, weekly for 9 weeks, irinotecan 90 mg/m(2) day 1, on weeks 1, 3, 5, 7 and 9, and etoposide 60 mg/m(2) days 1-3, on weeks 2, 4, 6, 8), or arm B (cisplatin 60 mg/m(2) day 1, irinotecan 60 mg/m(2) days 1, 8, 15, and etoposide 50 mg/m(2) days 1-3, every 4 weeks for four cycles). Prophylactic granulocyte colony-stimulating factor support was provided in both arms. RESULTS: Full cycles were delivered to 73% and 70% of patients in arms A and B, respectively. Incidences of grade 3-4 neutropenia, anemia, thrombocytopenia, infection and diarrhea were 57, 43, 27, 7 and 7%, respectively, in arm A, and 87, 47, 10, 13 and 10%, respectively, in arm B. A treatment-related death developed in one patient in arm A. Complete and partial response rates were 7% and 77%, respectively, in arm A, and 17% and 60%, respectively, in arm B. Median survival time was 8.9 months in arm A, and 12.9 months in arm B. CONCLUSIONS: Arm B showed a promising complete response rate and median survival with acceptable toxicity in patients with E-SCLC, and should be selected for the investigational arm in phase III trials.

Aged↗
PubMed2002

Intravenous immunoglobulin (IVIG) preparations induce apoptosis in TNF-alpha-stimulated endothelial cells via a mitochondria-dependent pathway.

Endothelial cells (ECs) are a target in inflammation, and the death of EC is regulated by various factors. Although intravenous immunoglobulin (IVIG) preparations are known to be beneficial therapeutic agents for the treatment of autoimmune diseases and systemic inflammatory disorders, their mechanism of action have not yet been completely elucidated. The aim of the present study is to investigate the possible role of IVIG in EC apoptosis. We demonstrate herein that IVIG induced the apoptosis of human umbilical vein ECs (HUVECs) prestimulated by TNF-alpha in vitro, but not in unstimulated HUVECs, in a dose- and time-dependent manner, using a proportion of cells with hypodiploid DNA, DNA ladder formation and morphological changes. Anti-Fas MoAbs had no effect on the IVIG-induced apoptosis in the TNF-alpha-stimulated HUVECs. IVIG decreased the intracellular expression of anti-apoptotic proteins of the Bcl-2 family (A1 and Bcl-XL) while IVIG increased the intracellular expression of pro-apoptotic proteins (Bax and Bcl-XS) in the TNF-alpha-stimulated HUVECs. Furthermore, IVIG increased the intracellular production of reactive oxygen species and decreased the mitochondrial membrane potential (Delta(psi)m). Caspase-inhibitors inhibited the IVIG-induced apoptosis of the TNF-alpha-stimulated HUVECs. The present results show a novel action in which IVIG can induce the apoptosis of TNF-alpha-stimulated HUVECs through a mitochondrial apoptotic signalling pathway. These observations suggest that the clinical use of IVIG preparations may thereby regulate the cell death of activated ECs in inflammation.

Apoptosis↗
PubMed2002

CD57+ T cells augment IFN-gamma production in a one-way mixed lymphocyte reaction and their expansion after stem cell transplantation in paediatric patients.

To clarify the immune response of CD57+ T cells (most of them are CD8+) in peripheral blood (PB) against alloantigens in order to elucidate the T helper 1 (Th 1) immune response, we assessed the role of CD57+ T cells in IFN-gamma (one of the representative Th 1 cytokines) production in a one-way mixed lymphocyte reaction (MLR). In this study, we showed that CD57+ T cells in responder cells were essential for effective IFN-gamma production in allogeneic MLR due partly to the augmentation of the alloresponse of regular T cells. Furthermore, IFN-gamma production in MLR correlated with the proportions of CD57+ T cells in PB regardless of the responders' age. We also showed that the extent of the expansion of CD57+ T cells in paediatric patients after haematopoietic stem cell transplantation (HSCT) was markedly lower than that in adult patients. In addition, CD57+ T cells purified and activated with a combination of cytokines showed a greater cytotoxicity than regular T cells against human umbilical vein endothelial cells. Because IFN-gamma production in one-way MLR is a useful predictor of graft-versus-host disease (GVHD), especially in the acute phase that occurs after allogeneic HSCT, our findings suggested that CD57+ T cells play a role in the development of GVHD and thus may explain the reason as to why a higher donor age is associated with an increased risk of developing GVHD while, in addition, the incidence of severe GVHD in paediatric patients is lower than that in adult patients.

Adult↗
PubMed2002

Characteristic profile of intestinal microflora in Kawasaki disease.

UNLABELLED: To investigate whether the ecology of the intestinal microflora may change in the acute phase of Kawasaki disease (KD), the distribution pattern was studied of common micro-organisms in feces from 20 patients with KD, 20 patients with acute febrile diseases (disease control) and 20 healthy children. KD patients had a significantly lower (p < 0.001) incidence of Lactobacillus (2/20, 10%) than disease control patients (16/20, 80%) and healthy children (14/20, 70%). KD patients had no significant incidences of other microbial genera, compared with both disease control and healthy children. CONCLUSION: The results suggest that a lack or loss of the beneficial Lactobacillus genus in the enteric microflora may occur during the acute phase of KD.

Case-Control Studies↗
PubMed2002

Relationship between objective responses in phase I trials and potential efficacy of non-specific cytotoxic investigational new drugs.

BACKGROUND: Although the evaluation of new investigational drugs in phase I, II and III trials requires considerable time and patient resources, only a few of these drugs are ultimately established as anticancer drugs. MATERIALS AND METHODS: We collected papers of phase I trials by a Medline search using the key words 'Neoplasms/Drug Therapy in MeSH' and 'Phase I' for the period from 1976 to 1993. A drug was defined as 'effective' if a regimen including the drug produced positive results in at least one phase III trial. We analyzed the relationship between objective (complete and partial) responses in phase I trials and the effectiveness of agents in phase III trials. RESULTS: A total of 399 single-agent phase I trials of cytotoxic agents in adult patients with solid tumors were obtained. Further clinical investigation was not recommended in 36 trials (9%) because of severe toxicity. In the remaining 363 trials, 174 drugs were evaluated and the median number of trials for each drug was two (range one to nine). Objective responses were observed in 495 (4.1%) of 12 076 patients, 178 (49%) of 363 trials, and 115 (66%) of 174 drugs. Of the 174 drugs, 48 (28%) were considered to be effective. Percentages of effective drugs rose as the number of responders in phase I trials increased. Logistic regression analyses showed the number of responders to be significantly associated with drug effectiveness [odds ratio = 1.16 (1.06-1.27), P = 0.001 for 174 drugs; odds ratio = 1.16 (1.05-1.28), P = 0.0038 for 363 trials]. Although 10 active drugs failed to produce an objective response in phase I trials, seven of them produced a tumor regression of <50%, and three reportedly produced objective responses in phase I trials conducted before 1975. The numbers of responders among patients with lung, ovarian, breast or colorectal cancer, but not those among patients with lymphoma, melanoma, sarcoma or renal-cell carcinoma, were associated significantly with drug effectiveness against the respective tumors. CONCLUSIONS: Objective responses observed in phase I trials are important for determining the future development of an anticancer drug.

Antineoplastic Agents↗