Niho N  Mutoh M  Sakano K  Takahashi M  Hirano S  Nukaya H  Sugimura T  Wakabayashi K 《Cancer science》2006,97(4):248-251

A new flavone derivative, chafuroside, has been isolated as a strong anti-inflammatory compound from oolong tea leaves, and its structure determined to be (2R,3S,4S,4aS,11bS)-3,4,11-trihydroxy-2-(hydroxymethyl)-8-(4-hydroxyphenyl)-3,4,4a,11b-tetrahydro-2H,10H-pyrano[2',3':4,5]furo[3,2-g]chromen-10-one. To assess its potential to inhibit intestinal carcinogenesis, 2.5, 5 and 10 p.p.m. chafuroside was given in the diet to Apc-deficient Min mice for 14 weeks from 6 weeks of age. Total numbers of polyps were reduced to 83, 73 and 56% of the control value, respectively. Moreover, dietary administration at 10 and 20 p.p.m. reduced azoxymethane (AOM)-induced colon aberrant crypt foci (ACF) development in rats to 69% of the AOM-treated control value with the higher dose. Chafuroside-associated toxicity was not observed at 2.5-10 p.p.m. in Min mice and 10-20 p.p.m. in AOM-treated rats. These results suggest that chafuroside might be a good chemopreventive agent for colon cancer.  相似文献   

  总被引：4，自引：0，他引：4  

Kimura H  Fujiwara Y  Sone T  Kunitoh H  Tamura T  Kasahara K  Nishio K 《Cancer science》2006,97(7):642-648

Epidermal growth factor receptor (EGFR) mutations are a strong determinant of tumor response to gefitinib in non-small cell lung cancer (NSCLC). We attempted to elucidate the feasibility of EGFR mutation detection in cells of pleural effusion fluid. We obtained 24 samples of pleural effusion fluid from NSCLC patients. The pleural effusion fluid was centrifuged, and the cellular components obtained were used for detection. EGFR mutation status was determined by a direct sequencing method (exons 18-21) and by the Scorpion Amplified Refractory Mutation System (ARMS) method. EGFR mutations were detected in eight cases. Three mutations were detected by both methods, and the other five mutations were detected by Scorpion ARMS alone. The mutations were detected by both methods in all four partial responders among the seven patients who received gefitinib therapy. Direct sequencing detected the mutations in only two of four cases with partial response. These results suggest that the DNA in pleural effusion fluid can be used to detect EGFR mutations. The Scorpion ARMS method appears to be more sensitive for detecting EGFR mutations than the direct sequencing method.  相似文献   

    

Kohno T  Kunitoh H  Toyama K  Yamamoto S  Kuchiba A  Saito D  Yanagitani N  Ishihara S  Saito R  Yokota J 《Cancer science》2006,97(8):724-728

Adenocarcinoma (ADC) is the most frequent histological type of lung cancer and comprises the majority of lung cancers in non-smokers. Thus, genetic factors responsible for ADC susceptibility need to be determined to establish efficient ways of preventing the disease. The OGG1 gene, encoding a glycosylase for 8-hydroxyguanine, an oxidatively damaged promutagenic base, has the polymorphism Ser326Cys, and OGG1-326Cys protein was indicated to have a lower ability to prevent mutagenesis than the OGG1-326Ser protein. Case-control studies to date suggest that the OGG1-326Cys allele is associated with a higher risk for several types of cancers, including overall lung cancer. However, the contribution of this polymorphism to lung ADC risk is unclear. In the present study, the OGG1-Ser326Cys polymorphism was assessed for association with lung ADC risk using a case-control study of a Japanese population consisting of 1097 cases and 394 controls. Odds ratios (OR) of the 326Cys allele carriers increased in a dose-dependent manner with allele number (P for the trend test = 0.04). The OR of homozygotes for the 326Cys allele was increased significantly when homozygotes for the 326Ser allele were used as a reference (OR = 1.5, 95% confidence interval [CI] = 1.0-2.1, P = 0.04). Furthermore, the overall OR for lung ADC of the Cys/Cys homozygotes out of a total of 1925 ADC patients and 3449 controls from six case-control studies reported up to the present were 1.43 (95% CI = 1.11-1.84, P = 0.0045). These results indicate that OGG1-326Cys functions as a risk allele for lung ADC development.  相似文献   

  总被引：3，自引：0，他引：3  

Saito S  Ito K  Nagase S  Suzuki T  Akahira J  Okamura K  Yaegashi N  Sasano H 《Cancer science》2006,97(12):1308-1314

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Kiyotaka YOH  Makoto TAHARA  Kenji KAWADA  Hirofumi MUKAI  Masanobu NAKATA  Kuniaki ITOH  Mitsuhiko KAWASHIMA  Hideki NISHIMURA  Ryuichi HAYASHI  Takashi OGINO  Hironobu MINAMI 《Asia-Pacific Journal of Clinical Oncology》2006,2(4):180-184

Background: Olfactory neuroblastoma is a rare sino‐nasal tumor arising from the olfactory epithelium and is often characterized by local invasion or metastasis. The role of chemotherapy in the treatment of this tumor is unclear. The purpose of this study was to review our institution’s experience of chemotherapy for advanced or recurrent olfactory neuroblastoma. Methods: Twenty‐one patients with histologically proven olfactory neuroblastoma were treated at our institution between 1992 and 2002. Twelve of these patients received chemotherapy in the setting of unresectable or recurrent disease and were retrospectively reviewed for clinical characteristics, treatment outcome or survival. Results: Eight patients of the 12 patients received cisplatin‐based chemotherapy and the remaining four patients received chemotherapy consisting of docetaxel plus irinotecan (three patients) or cyclophosphamide, doxorubicin, and vincristine (1 patient). A partial response was achieved in five patients, with an overall response rate of 42%, although the chemotherapeutic regimens were heterogeneous. Two partial responses were obtained among the three patients who received docetaxel plus irinotecan. The response rate to chemotherapy was 83% in the younger age group (<40 years), as opposed to 0% in the older age group (≥40 years), and the difference between the two groups was statistically significant (P = 0.02). Conclusion: Our study indicated that olfactory neuroblastoma would be sensitive to chemotherapy, especially with young patients. Docetaxel plus irinotecan has the possibility of showing favorable response, and warrants further investigation.  相似文献   

    

Kitahashi T  Takahashi M  Yamada Y  Oghiso Y  Yokohira M  Imaida K  Tsutsumi M  Takasuka N  Sugimura T  Wakabayashi K 《Cancer science》2008,99(2):241-245

Epidermal growth factor receptor ( EGFR ) gene alterations have been found in human lung cancers. However, there is no information on the factors inducing EGFR mutations. In rodents, K- ras mutations are frequently found in many lung carcinogenesis models, but hitherto, Egfr mutations have not been reported. Their presence was therefore investigated in representative lung carcinogenesis models with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N -nitrosobis(2-hydroxypropyl)amine (BHP), 2-amino-3,8-dimethylimidazo[4,5- f ]quinoxaline (MeIQx) and ethyl carbamate (urethane), as well as X-ray irradiation. With the chemical carcinogenesis models, no mutations were detected in Egfr , which is in clear contrast to the high rates observed in either codon 12 or 61 of K- ras (21/23 of the lung tumors induced with NNK, 4/5 with MeIQx, 1/4 with urethane and 7/18 with BHP). However, in the X-ray-induced lung tumors, Egfr mutations with amino acid substitution were observed in exons 18 and 21 (4/12, 33%), but no activating mutation of K- ras was detected. In addition, one and four silent mutations were identified in K- ras (exon 1) and Egfr (exons 18, 20 and 21), respectively. Most mutations in both Egfr and K- ras were G/C→A/T transitions (7/8, 88% and 31/34, 91%, respectively). Although, the mutational patterns in equivalent human lesions were not completely coincident, this first report of Egfr mutations in an experimental lung tumor model suggests that X-rays or other factors producing oxygen radicals could cause EGFR mutations in some proportion of lung cancers in humans. ( Cancer Sci 2008; 99: 241–245)  相似文献   

    

Ogawa Y  Tobinai K  Ogura M  Ando K  Tsuchiya T  Kobayashi Y  Watanabe T  Maruyama D  Morishima Y  Kagami Y  Taji H  Minami H  Itoh K  Nakata M  Hotta T 《Cancer science》2008,99(1):140-144

The purpose of this phase I and II study was to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of bortezomib in Japanese patients with relapsed or refractory multiple myeloma. This was a dose-escalation study designed to determine the recommended dose for Japanese patients (phase I) and to investigate the antitumor activity and safety (phase II) of bortezomib administered on days 1, 4, 8, and 11 every 21 days. Thirty-four patients were enrolled. A dose-limiting toxicity was febrile neutropenia, which occurred in one of six patients in the highest-dose cohort in phase I and led to the selection of 1.3 mg/m² as the recommended dose. Adverse events ≥ grade 3 were rare except for hematological toxicities, although there was one fatal case of interstitial lung disease. The overall response rate was 30% (95% confidence interval, 16–49%). Pharmacokinetic evaluation showed a biexponential decline, characterized by a rapid distribution followed by a longer elimination, after dose administration, whereas the area under the concentration–time curve increased proportionately with the dose. Bortezomib was effective in Japanese patients with relapsed or refractory multiple myeloma. A favorable tolerability profile was also seen, although the potential for pulmonary toxicity should be monitored closely. The pharmacokinetic and pharmacodynamic profiles of bortezomib in the present study warrant further investigations, including more relevant administration schedules. ( Cancer Sci 2008; 99: 140–144)  相似文献   

    

Tokuda Y  Tajima T  Narabayashi M  Takeyama K  Watanabe T  Fukutomi T  Chou T  Sano M  Igarashi T  Sasaki Y  Ogura M  Miura S  Okamoto S  Ogita M  Kasai M  Kobayashi T  Fukuda H  Takashima S  Tobinai K;Autologous Bone Marrow Transplantation Study Group;Breast Cancer Study Group of the Japan Clinical Oncology Group 《Cancer science》2008,99(1):145-151

A randomized controlled trial was conducted to evaluate the efficacy of high-dose chemotherapy (HDC) as consolidation of the treatment of high-risk postoperative breast cancer. Patients under 56 years of age with stage I to IIIB breast cancer involving 10 or more axillary lymph nodes were eligible. The primary endpoint was relapse-free survival (RFS). Between May 1993 and March 1999, 97 patients were enrolled, and two patients became ineligible. The median age of the 97 patients was 46 years (range 27–55 years), and 72 (74%) were premenopausal. The median number of involved axillary nodes was 16 (range 10–49). All patients had undergone a radical mastectomy. Major characteristics were well balanced between the treatment arms. Forty-eight patients in the standard-dose (STD) arm received six courses of cyclophosphamide, doxorubicin, and 5-fluorouracil followed by tamoxifen. Forty-nine patients were assigned to undergo HDC with cyclophosphamide and thiotepa after six courses of cyclophosphamide, doxorubicin, and 5-fluorouracil followed by tamoxifen; however, 15 of these patients (31%) did not undergo HDC. HDC was well tolerated without any treatment-related mortality. At a median follow-up of 63 months, the 5-year RFS of 47 eligible patients in the STD arm and 48 eligible patients in the HDC arm was 37% and 52% on an intent-to-treat basis, respectively ( P  = 0.17). Five-year overall survival of all randomized patients was 62% for the STD arm and 63% for the HDC arm ( P  = 0.78). Although the prespecified values of the two arms were not so accurate as to allow detection of the observed difference, no advantage of HDC was observed in terms of RFS or overall survival. ( Cancer Sci 2008; 99: 145–151)  相似文献   

    

Yahagi N  Shimano H  Hasegawa K  Ohashi K  Matsuzaka T  Najima Y  Sekiya M  Tomita S  Okazaki H  Tamura Y  Iizuka Y  Ohashi K  Nagai R  Ishibashi S  Kadowaki T  Makuuchi M  Ohnishi S  Osuga J  Yamada N 《European journal of cancer (Oxford, England : 1990)》2005,41(9):1316-1322

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  总被引：2，自引：0，他引：2  

Nagashima T  Hashimoto H  Oshida K  Nakano S  Tanabe N  Nikaido T  Koda K  Miyazaki M 《Breast cancer (Tokyo, Japan)》2005,12(3):216-220

BACKGROUND: Breast microcalcifications are difficult to depict by ultrasound (US). However, recent advances in US equipment and the refinement of breast imaging techniques have improved the detection and characterization of small breast lesions. The present study attempts to determine whether US examination is able to demonstrate nonpalpable breast lesions associated with mammographically detected microcalcifications without mass density or distortion, and to evaluate the clinical reliability of US-guided procedures, especially in cases of ductal carcinoma in situ(DCIS)of the breast. METHODS: The subjects consisted of 73 patients with breast cancer diagnosed preoperatively as DCIS by stereotactic core needle biopsies, all of whom had microcalcifications without other abnormalities on mammography. The radiological appearance and size of the clustered microcalcifications were evaluated. US examinations were performed preoperatively, and the detection rates were assessed. Sonographically detected lesions underwent US-guided wire localization followed by surgical excision. RESULTS: The lesions associated with microcalcifications were identified sonographically in 54 of 73 cases (74%), and the pathological examination revealed breast cancer in all of the corresponding specimens. Lesions with linear-branching shape, segmental-linear distribution and category-5 calcifications on mammography had a high level of visibility on US. The US visible cases had a larger size of calcified area on mammography when compared with US invisible cases. Pathologically, the lesions were more frequently seen on US in cases with minimally invasive cancer or with comedo type DCIS. CONCLUSIONS: US examination is an effective method for identifying and localizing breast microcalcifications, and can be used as an alternative to stereotactic localization in selected patients with early breast cancer.  相似文献