Ogawara D.,Sasebo Central Hospital |
Fukuda M.,Nagasaki Municipal Hospital |
Nakamura Y.,Nagasaki University |
Kohno S.,Nagasaki University
Cancer Management and Research | Year: 2010
Long-term survival is quite uncommon in refractory small cell lung cancer (SCLC) patients, with less than 25% of patients with limited-stage disease and 1%-2% of patients with extensive-stage disease remaining alive at five years. Recent clinical studies have demonstrated the promising efficacy of amrubicin for patients with relapsed SCLC. This review presents the results of clinical studies showing the efficacy and safety of amrubicin for the treatment of relapsed SCLC. Amrubicin is a synthetic anthracycline agent with a similar structure to doxorubicin, in which the hydroxyl group at position 9 in amrubicin is replaced by an amino group to enhance efficacy. It is converted to an active metabolite, amrubicinol, which is 5-54 times more active than amrubicin. Amrubicin and amrubicinol are inhibitors of DNA topoisomerase II, exerting their cytotoxic effects by stabilizing a topoisomerase II-mediated cleavable complex. The toxicity of amrubicin is similar to that of doxorubicin, although amrubicin shows almost no cardiotoxicity. In the relevant trials, amrubicin was administered intravenously at a dose of 35-40 mg/m2 on days 1-3 every three weeks. The response rate was 34%-52% and median survival times were 8.1-12.0 months. Common hematologic toxicities included neutropenia, leucopenia, anemia, thrombocytopenia, and febrile neutropenia. Nonhematologic adverse events included Grade 3-4 anorexia, asthenia, hyponatremia, and nausea. The results of the studies which demonstrated the efficacy of monotherapy for relapsed SCLC involved mainly Japanese patients. Therefore, it is necessary to conduct more clinical studies in non-Japanese patients to confirm the efficacy of amrubicin. © 2010 Ogawara et al, publisher and licensee Dove Medical Press Ltd.
Yoshizawa K.,Hoshi University |
Narita M.,Hoshi University |
Mori T.,Hoshi University |
Miyatake M.,Hoshi University |
And 4 more authors.
Addiction Biology | Year: 2012
Substitutions of the dopamine D2 or D3 receptor agonists for the discriminative stimulus effect induced by U-50,488H, methamphetamine (METH) and cocaine in rats were examined. The D2 receptor agonist R-propylnorapomorphine [(-)-NPA] failed to substitute for U-50,488H cue, while the D3 receptor-preferred agonist (+/-)-7-hydroxy-dipropylaminotetralin hydrobromide (7-OH-DPAT) produced dose-related increases in drug-appropriate responding up to 0.03 mg/kg, which fully substituted. At doses greater than 0.03 mg/kg of 7-OH-DPAT, there was a dose-dependent decrease in the percentage of responses on the U-50,488H-appropriate lever. Furthermore (-)-NPA and 7-OH-DPAT at high doses substituted for the discriminative stimulus effect induced by both METH and cocaine, indicating that 7-OH-DPAT at high doses may interact with D2 receptors. These results suggest that the stimulation of D2 receptor may be critical for the production of the discriminative stimulus effect induced by METH and cocaine, whereas the stimulation of D3 receptor may contribute to the production of the U-50,488H cue. © 2010 The Authors, Addiction Biology © 2010 Society for the Study of Addiction.
Iwanaga M.,Nagasaki University |
Iwanaga M.,Kwassui Women's College |
Watanabe T.,Tokyo Medical University |
Utsunomiya A.,Imamura Bun in Hospital |
And 16 more authors.
Blood | Year: 2010
Definitive risk factors for the development of adult T-cell leukemia (ATL) among asymptomatic human T-cell leukemia virus type I (HTLV-1) carriers remain unclear. Recently, HTLV-1 proviral loads have been evaluated as important predictors of ATL, but a few small prospective studies have been conducted. We prospectively evaluated 1218 asymptomatic HTLV-1 carriers (426 males and 792 females) who were enrolled during 2002 to 2008. The proviral load at enrollment was signifi-cantly higher in males than females (median, 2.10 vs 1.39 copies/100 peripheral blood mononuclear cells [PBMCs]; P < .001), in those 40 to 49 and 50 to 59 years of age than that of those 40 years of age and younger (P = .02 and .007, respectively), and in those with a family history of ATL than those without the history (median, 2.32 vs 1.33 copies/100 PBMCs; P = .005). During follow-up, 14 participants progressed to overt ATL. Their baseline proviral load was high (range, 4.17-28.58 copies/100 PBMCs). None developed ATL among those with a baseline proviral load lower than approximately 4 copies. Multivariate Cox analyses indicated that not only a higher proviral load, advanced age, family history of ATL, and first opportunity for HTLV-1 testing during treatment for other diseases were independent risk factors for progression of ATL. © 2010 by The American Society of Hematology.
Nakamura Y.,Nagasaki University |
Sano K.,Meiji Pharmaceutical University |
Soda H.,Sasebo General Hospital |
Takatani H.,Red Cross |
And 6 more authors.
Journal of Thoracic Oncology | Year: 2010
Introduction: We assessed the relationship between the plasma concentration of gefitinib and its efficacy in Japanese patients with advanced non-small cell lung cancer (NSCLC). Methods: Plasma trough levels of gefitinib were measured on days 3 (D3) and 8 (D8) by high-performance liquid chromatography in 44 patients with advanced NSCLC treated with 250 mg gefitinib daily. Eligibility criteria included performance status ≤3, age ≤ 80 years, and stages IIIB-IV cancer. Epidermal growth factor receptor mutations in 23 patients were analyzed retrospectively. Results: The median plasma gefitinib values were 662 ng/ml on D3 and 1064 ng/ml on D8, and the D8/D3 ratio was 1.587. The median progression-free survival (PFS) was 71 days, and the median overall survival was 224 days. Adenocarcinoma, never smoking, and high D8/D3 ratio were associated with better PFS. Multivariate analysis showed that PFS was associated with never smoking and high D8/D3 ratio. Never-smokers with a high D8/D3 ratio showed the best PFS. Overall survival was not associated with the D8/D3 ratio. Epidermal growth factor receptor mutation analysis of 23 patients showed that 15 patients had exon 19 deletion and/or exon 21 point mutation. Median PFS was similar between mutation-positive and mutation-negative individuals in the high D8/D3 group, whereas mutation-negative individuals in the low D8/D3 group showed the worst median PFS. Conclusions: A high D8/D3 ratio was independently associated with better PFS in patients with NSCLC treated with gefitinib. Our findings suggest that the pharmacokinetics of gefitinib may be involved in its antitumor activity. © 2010 by the International Association for the Study of Lung Cancer.
Sagara Y.,Nagasaki University |
Miyata Y.,Nagasaki University |
Nomata K.,Nagasaki Municipal Hospital |
Hayashi T.,Nagasaki University |
Kanetake H.,Nagasaki University
Cancer Epidemiology | Year: 2010
Background: Green tea polyphenol (GTP) suppresses malignancy in bladder cancer cell lines. However, the detail of its anti-carcinogenic effect in vivo is not fully understood. This study investigated the effect of GTP on bladder tumor size and angiogenesis in mice given N-butyl-(-4-hydroxybutyl) nitrosamine (BBN), with and without GTP. Methods: Eight-week-old female C3H/He mice were treated with and without 0.05% BBN solution for 14 or 24 weeks. In addition, they were also treated with and without 0.5% GTP solution for the same periods. Histopathological diagnosis was established using hematoxylin and eosin staining, and microvessel density (MVD) was estimated by counting CD34- and von Willebrand factor-positive vessels in the tumor area. Results: At 14 weeks, cancer cells were detected in BBN and BBN + GTP mice [5/14 (35.7%) and 3/14 (21.4%), respectively, p = 0.678]. At 24 weeks, the incidence of cancer cells was also similar between the groups (BBN + GTP: 61.9% vs. BBN: 82.6%; p = 0.179). However, the frequency of invasive tumors in BBN + GTP mice was significantly lower (23.8%; p = 0.030) than in those given BBN alone (65.2%). Tumor volume and MVD of intratumoral and stromal region in the BBN + GTP group were also significantly lower than in BBN mice. Conclusion: The results showed that GTP had no anti-carcinogenic effect, but inhibited tumor growth and invasion in mice with established bladder cancer, at least in part through the regulation of angiogenesis. Our data suggest that GTP seems to suppress tumor development in bladder cancer. © 2010 Elsevier Ltd. All rights reserved.
Harada Y.,Nagasaki University |
Kinoshita F.,Nagasaki Municipal Hospital |
Yoshida L.M.,Nagasaki University |
Le Nhat M.,Nagasaki University |
And 6 more authors.
Pediatric Infectious Disease Journal | Year: 2013
Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection in children less than 5 years of age. The impact of non-RSV respiratory virus coinfection on the severity of RSV disease is unknown. Methods: This hospital-based prospective study was conducted in Nagasaki, Japan, on all children less than 5 years of age with acute respiratory infection (ARI) who had undergone a rapid RSV diagnostic test between April 2009 and March 2010. Thirteen respiratory viruses were identified from nasopharyngeal swab samples using a multiplex polymerase chain reaction; polymerase chain reaction-positive samples were considered as confirmed respiratory virus infections. The cases were classified into 3 categories (pneumonia, moderate-to-severe nonpneumonic ARI and mild ARI) according to the findings of the chest radiograph and the hospitalization records. Results: Among 384 cases enrolled, 371 were eligible for analysis, of whom 85 (23%) were classified as pneumonia cases; 137 (37%) as moderate-to-severe nonpneumonic ARI cases and 162 (40%) as mild ARI cases. RSV was detected in 172 cases (61.6%), and 31 cases (18.0%) had double or triple infections with other respiratory viruses. RSV infection was more frequently observed in pneumonia cases (odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.31-3.9) and moderate-to-severe nonpneumonic ARI cases (OR: 2.95; 95% CI: 1.82-4.78) than in mild ARI cases. The association with moderate-to-severe nonpneumonic ARI cases was stronger with RSV/non-RSV respiratory virus coinfection (adjusted OR: 4.91; 95% CI: 1.9-12.7) than with RSV single infection (adjusted OR: 2.77; 95% CI: 1.64-4.7). Conclusions: Non-RSV respiratory virus coinfection is not uncommon in RSV-infected children and may increase the severity of RSV disease. Copyright © 2013 by Lippincott Williams & Wilkins.
Tsutsui S.,Nagasaki University |
Ashizawa K.,Nagasaki University |
Minami K.,Nagasaki Municipal Hospital |
Tagawa T.,Nagasaki University |
And 3 more authors.
American Journal of Roentgenology | Year: 2010
OBJECTIVE. The purpose of this study was to evaluate the clinical significance of multiple focal pure ground-glass opacities (GGOs) on high-resolution CT images of patients with lung cancer. MATERIALS AND METHODS. The cases of 23 patients with proven lung cancer and associated multiple focal pure GGOs on high-resolution CT images were retrospectively reviewed. The number, size, distribution, and morphologic characteristics of focal pure GGOs were evaluated. Serial changes in focal pure GGOs that were not surgically resected were analyzed at follow-up high-resolution CT. RESULTS. The number of focal pure GGOs was 196 in total. The size of the opacities ranged from 2 to 30 mm in largest diameter. Lung cancer and focal pure GGOs were seen in the same lobe and/or in the other lobes. One hundred seventy-one of the lesions (87%) had a well-defined border or round shape. Histologic findings were obtained for 15 lesions representing 74 focal pure GGOs that were surgically resected: 11 atypical adenomatous hyperplasia lesions, three bronchioloalveolar carcinomas, and one lesion of focal fibrosis. In 110 of the cases of focal pure GGOs, all of which were followed up with HRCT for a median duration of 1,351 days, the size of 105 lesions (95%) did not change, the size of one decreased, and four lesions disappeared. CONCLUSION. The size of most focal pure GGOs associated with lung cancer did not change during the follow-up period. Most of the small number of lesions histologically diagnosed were atypical adenomatous hyperplasia or bronchioloalveolar carcinoma. These data justify the therapeutic strategy of resecting the primary tumor without therapeutic intervention in the remaining focal pure GGOs. © American Roentgen Ray Society.
Mori R.,Nagasaki University |
Tanaka K.,Nagasaki University |
De Kerckhove M.,Nagasaki University |
De Kerckhove M.,Nagasaki Municipal Hospital |
And 10 more authors.
American Journal of Pathology | Year: 2014
The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1 +/- mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a-/- mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1+/- mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring. © 2014 American Society for Investigative Pathology.
Kawashiri S.-Y.,Nagasaki University |
Suzuki T.,Nagasaki University |
Okada A.,Nagasaki University |
Yamasaki S.,Nagasaki University |
And 8 more authors.
Modern Rheumatology | Year: 2013
Objective: We investigated whether musculoskeletal ultrasonography (MSKUS) assists the diagnostic performance of the 2010 rheumatoid arthritis (RA) classification criteria. Methods: Sixty-nine early arthritis patients were consecutively enrolled. None of the patients had been treated. In MSKUS of bilateral wrist and finger joints from 22 sites, the findings obtained by gray-scale and power Doppler (PD) assessment were graded on a semiquantitative scale from 0 to 3. Plain magnetic resonance imaging (MRI) of both wrist and finger joints was also examined. Diagnosis of RA was defined by the initiation of disease-modifying antirheumatic drugs within the first 3 months. The diagnostic performance of the patients was evaluated at entry using 2010 RA classification criteria in conjunction with MSKUS. Results: The indispensable MSKUS finding for differentiating RA was the presence of a PD grade 2 or 3 that was superior to 2010 RA classification criteria or MRI-proven bone edema. We propose that the decision tree algorithm of 2010 RA classification criteria with PD grade 2 or 3 reveals the best discriminative ability. Conclusion: MSKUS, especially with a strong PD signal, is very useful to assist the diagnostic performance of the 2010 RA classification criteria in the early recognition of RA. © 2012 Japan College of Rheumatology.
PubMed | Nagasaki Municipal Hospital
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016
17108 Background: VNR is one of standard drugs for elderly NSCLC. The role of platinum- based combination chemotherapy for elderly pts is controversial.Based on our phase I study (Fukuda, et al, abstract 2763, ASCO 2002), we conducted a phase II single arm study of VNR combined with CBDCA for elderly NSCLC pts. Primary endpoints were response and toxicity. Eligibility criteria included: chemotherapy-nave, good performance status (PS: 0-2), age 75, stage IIIB-IV, and adequate hematological, hepatic and renal function, written informed consent. Treatment consisted of VNR 20 mg/mA total of 40 pts were enrolled. Pts characteristics: male/female = 30/10, PS 0/1 = 18/22, median age (range) = 78 (75-86), Ad/Sq/Others = 30/9/1, stage IIIB/IV = 14/26. Forty pts were eligible and assessable for toxicity and survival, and 37 pts were assessable for response on the submission of this abstract. Thirty-three pts were treated with two or more courses of treatment. Overall response rate was 13.5% (95% CI, 4.5%-28.8%); CR= 0, PR= 5, SD = 23, PD = 9. Grade 3 or 4 leukopenia, neutropenia, and anemia were observed in 31.6%, 50.0%, and 7.1%, respectively. Treatment-related death did not occurred. Non-hematological toxicity was mild. The median survival time was 392 days (95% CI, 311-474) and the median time to progression was 114 days.This combination is well-tolerated and modest activity in pts with elderly NSCLC. No significant financial relationships to disclose.