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81.
Intensification of antitumor effect by T helper 1-dominant adoptive immunogene therapy for advanced orthotopic colon cancer. 总被引:11,自引:0,他引:11
Mikihito Nakamori Makoto Iwahashi Masaki Nakamura Kentaro Ueda Xiaoliu Zhang Hiroki Yamaue 《Clinical cancer research》2003,9(6):2357-2365
PURPOSE: T helper (Th) 1/Th2 balance, controlled by Th1 or Th2 cells producing cytokines, plays important roles in antitumor immunity. Interleukin-18 (IL-18) can act together with IL-12 in promoting the generation of IFN-gamma producing Th1 cells. The goal of this study was to determine whether cytotoxic T lymphocyte (CTL) secreted in a murine IL-18-induced Th1-dominant state inhibited the development of primary tumors and synchronous liver metastases in orthotopic colon cancer model. EXPERIMENTAL DESIGN: Murine IL-18 gene was transduced into activated T lymphocytes by an adenovirus vector encoding IL-18 (AdIL-18) liposome complex method. Efficacy of adoptive immunogene therapy using AdIL-18 with or without IL-12 was tested in advanced orthotopic xenograft of murine colon cancer. To elucidate the mechanism responsible for the adoptive immunogene therapy, serum IL-4, IL-6, IFN-gamma, and tumor necrosis factor alpha production in Th1/Th2 cytokine balance and quantification of tumor vascularity were investigated. RESULTS: By a modified method of adenoviral gene transduction, T lymphocytes achieved efficient IL-18 production without cell toxicity. Against orthotopic colon cancer, when combined with low dose of recombinant (r) IL-12 (AdIL-18-CTL/rIL-12), the therapeutic efficacy showed much smaller tumors with no liver metastases and no disseminated tumors. There was a significant difference in the volume of primary tumors and the number of liver metastases compared with the group treated with AdIL-18-CTL alone or other group (P < 0.01). In addition, the median survival time of the group treated with AdIL-18-CTL was 53.7 +/- 5.8 days and that of AdIL-18-CTL/rIL-12 was 78.4 +/- 6.1 days, which was also a significant difference (P < 0.01). These antitumor mechanisms were involved with Th1-dominant response in serum Th1/Th2 cytokine balance and suppression of neovascularization at primary tumor site. CONCLUSION: These data suggest that a strategy of Th1/Th2 balance-based adoptive immunogene therapy might be useful for advanced cancer patients. 相似文献
82.
Pelvic insufficiency fractures in postmenopausal woman with advanced cervical cancer treated by radiotherapy. 总被引:3,自引:0,他引:3
Ichiro Ogino Naoyuki Okamoto Yoshimi Ono Tatsuo Kitamura Hiroki Nakayama 《Radiotherapy and oncology》2003,68(1):61-67
PURPOSE: To assess the predisposing factors and clinical characteristics of pelvic insufficiency fractures (PIF) in postmenopausal women with pelvic irradiation. MATERIAL AND METHODS: A total 335 postmenopausal patients with cervical cancer of the intact uterus treated with radiation therapy between 1983 and 1998 were reviewed. Total external dose was delivered between 45 and 50.4 Gy with parallel opposed anteroposterior portals. Total brachytherapy dose at point A was delivered between 10 and 36 Gy. PIF were diagnosed by bone scintigraphy and confirmed by computed tomography. The cumulative incidence of symptomatic PIF was estimated by actuarial methods. Potential risk factors (age, weight, type II diabetes, delivery, menopause, total external dose, total brachytherapy dose) were assessed. RESULTS: Fifty-seven (17.0%) of 335 patients were diagnosed as having PIF. Forty-seven patients were symptomatic and ten were asymptomatic. Parameters carrying a significant association with PIF were body weight 49 kg or below (P=0.044) in stepwise logistic regression analysis. The cumulative incidence of symptomatic PIF at 5 years was 17.9% calculated by the Kaplan-Meier method. A body weight of 49 kg or below and more than three deliveries were identified as having a significant effect on symptomatic PIF in univariate analysis (P=0.021, P=0.003, log-rank test) and Cox life table regression analysis (P=0.038, P=0.013). Five patients required narcotic agents and eight patients required hospital admission. CONCLUSIONS: We should consider reducing the dose contribution to the sacrum and sacroilac joints, without underdosing the tumor, especially in postmenopausal women with many deliveries or low body weight. 相似文献
83.
Takeshi Tominaga Hiroki Koyama Tetsuya Toge Shigeto Miura Keizo Sugimachi Susumu Yamaguchi Koichi Hirata Yasumasa Monden Yasuo Nomura Masakazu Toi Izo Kimijima Shinzaburo Noguchi Hiroshi Sonoo Kazuaki Asaishi Tadashi Ikeda Tadaoki Morimoto Jun Ota Yasuo Ohashi Osahiko Abe 《Journal of clinical oncology》2003,21(6):991-998
PURPOSE: We compared the therapeutic usefulness of doxifluridine (5'-DFUR) alone and a combination of 5'-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy. PATIENTS AND METHODS: A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5'-DFUR alone or 5'-DFUR plus CPM. All patients initially received 5'-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5'-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5'-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5'-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups. RESULTS: Of the 1,088 eligible women, 546 were assigned to receive 5'-DFUR alone and 542 were assigned to receive 5'-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5'-DFUR plus CPM than in those who received 5'-DFUR alone (log-rank test, P =.021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5'-DFUR group and 32.3% of patients (175 of 542) in the 5'-DFUR plus CPM group (chi(2) test, P <.001). CONCLUSION: Combination therapy with 5'-DFUR plus CPM is more effective in preventing recurrence than 5'-DFUR alone. 相似文献
84.
Asaka Takahashi Hiroki Matsuoka Keiichi Yamada Yasushi Uda 《Food and chemical toxicology》2005,43(4):521-528
3-Allyl-5-substituted 2-thiohydantoins (ATH-amino acids) derived from allyl isothiocyanate and amino acids can inhibit the mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in the Salmonella assay. In this report, we studied possible mechanisms for the inhibition using rat liver S9 in assays for ethoxyresorufin O-deethylase (EROD), a marker activity for cytochrome P450 1A (CYP1A), which activates heterocyclic amines, and the Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). Quantitative analysis of ATH-amino acids and IQ during incubation with rat liver S9 fraction by HPLC showed that ATH-amino acids could act as S9-inhibitors, thereby inhibiting metabolic activation of IQ. Among the tested ATH-amino acids, ATH-Phe, ATH-Trp, ATH-Leu and ATH-Val showed a dose-dependent inhibition of EROD activity. ATH-Gly, ATH-Glu, and ATH-Asp behaved as blocking agents toward N-hydroxy-IQ, but exhibited no inhibition of EROD activity. 相似文献
85.
Sanae Fukuda Hiroki Ishikawa Yasuhiro Koga Yuji Aiba Kazuko Nakashima Lei Cheng Taro Shirakawa 《The Journal of adolescent health》2004,35(2):156-158
We studied 867 junior high school children and administered a questionnaire documenting allergic symptoms and environmental variables, and measured Immunoglobulin E serum levels and the immunoglobulin G titers of serum antibody to microflora. A total of 716 subjects were ultimately used for statistics; those with at least two of the following allergic symptoms: asthma, rhinitis, eczema, or food allergy, showed significantly higher IgG titers to Bactroides vulgatus than other groups. This finding suggests that a species of the Bacteroides genus of the intestinal microflora tends to affect the gut issues, but further studies are needed to clarify this. 相似文献
86.
87.
Watanabe A Sasaki A Hirabayashi T Itoh M Abe T 《Kyobu geka. The Japanese journal of thoracic surgery》2000,53(13):1125-1128
A 58-year-old female was admitted to our hospital because of sudden dyspnea and general malaise. A continuous murmur was heard along the left sternal border. A chest X-ray showed cardiomegaly and pulmonary vascular marking. Doppler echocardiography confirmed the presence of an aneurysmatic mass, originating from the non-coronary sinus of Valsalva and extending to the right atrium, with a turbulent flow into the right atrium, aortic regurgitation (II/IV) and tricuspid regurgitation (III/IV). Ascending aortography demonstrated a communication between the aortic sinus and the right atrium. The pulmonary-to-systemic flow ratio was calculated to be 2.04. Oblique aortotomy and right atriotomy were performed. The aneurysm was resected and its origin was directly closed with horizontal mattress sutures through the aortic side and right atrial side. Perforation of a non-coronary cusp that caused aortic regurgitation was found following aortotomy and it was closed with an autologous pericardial patch. Tricuspid annuloplasty was performed using DeVega's technique. The postoperative course was uneventful, and she was discharged on the 10th postoperative day. 相似文献
88.
Long-lasting renal dysfunction following tacrolimus induction therapy in ulcerative colitis patients
Na Cha Naoki Oshima Kenichi Kishimoto Satoshi Kotani Eiko Okimoto Tomotaka Yazaki Hiroki Sonoyama Akihiko Oka Yoshiyuki Mishima Kotaro Shibagaki Hiroshi Tobita Kousaku Kawashima Norihisa Ishimura Shunji Ishihara 《Journal of Clinical Biochemistry and Nutrition》2022,70(3):297
Although tacrolimus (TAC) has remarkable effects in ulcerative colitis (UC) patients when given as remission induction therapy, some can develop renal dysfunction during TAC administration, resulting in withdrawal, though related details remain poorly understood. This study was conducted to determine the impact of oral TAC on renal function for remission induction therapy in UC patients. Fifty-five patients (10 elderly, 45 non-elderly) with UC and treated with oral TAC at our hospital were retrospectively evaluated. Renal function was assessed using estimated glomerular filtration rate (eGFR). Although a high clinical response to TAC was seen in both elderly and non-elderly, a decline in eGFR was noted in nearly all patients regardless of age, with a maximum change of −34.4% from the baseline value at week 11. Furthermore, eGFR decline recovered quickly after TAC discontinuation, though did not return to the baseline at two years following cessation. The rate of eGFR change at week 12 was significantly associated with patient age (β = −0.3242, p = 0.0103) and peak serum trough level during TAC treatment (β = 0.3563, p = 0.0051). Furthermore, the rate of decline in eGFR was significantly greater during treatment with TAC in the elderly as compared to non-elderly, with a large difference in eGFR decline rate between those groups also noted at two years after withdrawal of treatment. Careful attention to renal function when administering oral TAC for UC is important and changes in eGFR should be monitored closely in elderly patients even after treatment cessation. 相似文献
89.
Tomohiro Komatsu Makoto Ayaori Harumi Uto-Kondo Katsumi Hayashi Katsumi Tamura Hiroki Sato Makoto Sasaki Takafumi Nishida Shunichi Takiguchi Emi Yakushiji Kazuhiro Nakaya Katsunori Ikewaki 《Journal of atherosclerosis and thrombosis》2022,29(5):775
Aims: Inflammation is involved in various processes of atherosclerosis development. Serum C-reactive protein (CRP) levels, a predictor for cardiovascular risk, are reportedly reduced by statins. However, several studies have demonstrated that CRP is a bystander during atherogenesis. While S100A12 has been focused on as an inflammatory molecule, it remains unclear whether statins affect circulating S100A12 levels. Here, we investigated whether atorvastatin treatment affected S100A12 and which biomarkers were correlated with changes in arterial inflammation. Methods: We performed a prospective, randomized open-labeled trial on whether atorvastatin affected arterial (carotid and thoracic aorta) inflammation using18fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) and inflammatory markers. Thirty-one statin-naïve patients with carotid atherosclerotic plaques were randomized to either a group receiving dietary management (n=15) or one receiving atorvastatin (10mg/day,n=16) for 12weeks.18F-FDG-PET/CT and flow-mediated vasodilation (FMD) were performed, the latter to evaluate endothelial function. Results: Atorvastatin, but not the diet-only treatment, significantly reduced LDL-cholesterol (LDL-C, -43%), serum CRP (-37%) and S100A12 levels (-28%) and improved FMD (+38%).18F-FDG-PET/CT demonstrated that atorvastatin, but not the diet-only treatment, significantly reduced accumulation of18F-FDG in the carotid artery and thoracic aorta. A multivariate analysis revealed that reduction in CRP, S100A12, LDL-C, oxidized-LDL, and increase in FMD were significantly associated with reduced arterial inflammation in the thoracic aorta, but not in the carotid artery. Conclusions: Atorvastatin treatment reduced S100A12/CRP levels, and the changes in these circulating markers mirrored the improvement in arterial inflammation. Our observations suggest that S100A12 may be an emerging therapeutic target for atherosclerosis. 相似文献
90.
We herein describe a 68‐year‐old man with follicular mucinosis. A dermoscopic examination showed multiple, round, brownish yellow dots with a whitish rim in the follicular ostium and red dots in the interfollicular area. This case report is the first to suggest that follicular mucinosis shows these dermoscopic findings. 相似文献