共查询到20条相似文献,搜索用时 15 毫秒
1.
Rodolfo Passalacqua Carlo Buzio Sebastiano Buti Camillo Porta Roberto Labianca Debora Pezzuolo Roberta Camisa Roberto Sabbatini Luigi Benecchi Caterina Messina Rita Cengarle Augusto Vaglio Matteo Dalla Chiesa Gianluca Tomasello Caterina Caminiti 《Cancer immunology, immunotherapy : CII》2010,59(4):553-561
This is the first phase III randomised trial to evaluate maintenance immunotherapy in metastatic renal cell cancer (mRCC). Patients were randomised to receive treatment with a 4-week cycle of subcutaneous low doses IL-2 + IFN in months 1, 3 and 5, and then every 3 months until the first documented disease progression (arm A, suspension), or the same regimen, with chronic maintenance of immunotherapy, regardless of tumour response, until death or intolerable toxicity (arm B, maintenance). The primary endpoint was overall survival (OS); secondary endpoints were time from first progression to death (TFPTD) and tolerability. One hundred and eighty-three patients were enrolled between January 1998 and November 2003. After a median follow-up of 53.9 months, response rate, median OS and median TFPTD were 14.7% (6.3% CR) versus 11.3% (5.5% CR), 14 versus 14 months, 6 versus 5 months, in arms A and B, respectively with no significant differences between the groups. Cox regression analysis showed that the use of chemotherapy after first progression (HR 0.54; 95% CI 0.35–0.86; p = 0.008), PS = 0 (HR 0.53; 95% CI 0.35–0.81; p = 0.001) and female gender (HR 0.63; 95% CI 0.41–0.98; p = 0.038) were significantly associated with a longer TFPTD; treatment arm was not significant (HR 0.88; 95% CI 0.60–1.31; p = 0.54). Toxicity was mainly limited to WHO grades 1 or 2. Chronic maintenance immunotherapy after disease progression is feasible, but does not significantly increase OS or the TFPTD. 相似文献
2.
Wang S Zhang M Zeng Z Tian L Wu K Chu J Fan D Hu P Sung JJ Yu J 《Life sciences》2011,88(17-18):792-797
AimNuclear factor-kappa B inhibitor alpha (IκBα) polymorphisms were found to be associated with inflammatory diseases. However, the association between IκBα polymorphisms with gastric cancer is still unknown. We aim to investigate the association between IκBα polymorphisms and gastric cancer risk in a large population-based case–control study among southern Chinese.Main methodsA population-based case–control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 1010 gastric cancer patients and 1500 healthy controls were enrolled in this study. IκBα polymorphisms were identified by sequencing of IκBα gene ranging from the 2 kb promoter region to the 3.5 kb genomic region. Polymorphisms in IκBα were analyzed by TaqMan SNP genotyping assay.Key findingsrs17103265 deletion homozygote (?/?) had significantly increased gastric cancer risk (OR = 2.11, 95% CI = 1.17–3.83, P = 0.01), compared with rs17103265 T homozygote (TT). rs17103265 (?/?) genotype was significantly associated with increased risk of intestinal-type gastric cancer with (OR = 2.21, 95% CI = 1.19–4.08, P = 0.01), but not with the diffuse or mix type of gastric cancer. rs17103265 (?/?) was associated with poorly differentiated gastric cancer (OR = 2.05, 95% CI = 1.07–3.94, P = 0.03), but not with moderately or well differentiated gastric cancer. A significant decrease in luciferase activity was observed in rs17103265 deletion allele as compared with the vector containing the rs17103265 T allele (P < 0.0001). rs17103265 polymorphism was not associated with the prognosis of gastric cancer patients.SignificanceIκBα rs17103265 deletion homozygote is a novel genetic risk factor for gastric carcinogenesis, especially for the development of certain subtypes of gastric cancer in southern Chinese population. 相似文献
3.
Heidbreder M Zander C Malkusch S Widera D Kaltschmidt B Kaltschmidt C Nair D Choquet D Sibarita JB Heilemann M 《Biochimica et biophysica acta》2012,1823(10):1984-1989
In mammalian cells, inflammation is mainly mediated by the binding of tumor necrosis factor alpha to tumor necrosis factor receptor 1. In this study, we investigated lateral dynamics of TNF-R1 before and after ligand binding using high-density single-particle tracking in combination with photoactivated localization microscopy. Our single-molecule data indicates the presence of tumor necrosis factor receptor 1 with different mobilities in the plasma membrane, suggesting different molecular organizations. Cholesterol depletion led to a decrease of slow receptor species and a strong increase in the average diffusion coefficient. Moreover, as a consequence of tumor necrosis factor-alpha treatment, the mean diffusion coefficient moderately increased while its distribution narrowed. Based on our observation, we propose a refined mechanism on the structural arrangement and activation of tumor necrosis factor receptor 1 in the plasma membrane. 相似文献
4.
Cheng-lin Zhu Qiang Huang Chen-hai Liu Xian-sheng Lin Fang Xie 《Molecular biology reports》2013,40(11):6055-6062
The role of hypoxia-inducible factors-1 alpha (HIF-1α) expression in gastric cancer remains controversial. We performed a systematic review of the literature with meta-analysis. Electronic databases were used to identify published studies before December 1, 2012. Pooled hazard ratio (HR) or odds ratio (OR) with 95 % confidence interval (95 % CI) was used to estimate the strength of the association between HIF-1α expression and survival of gastric cancer patients. Heterogeneity and publication bias were also assessed. Final analysis of 1,268 patients from 9 eligible studies was performed. High HIF-1α expression was significantly correlated with poor overall survival (OS) of gastric cancer patients (HR = 2.14, 95 % CI = 1.32–3.48). Subgroup analysis indicated that HIF-1α over-expression had an unfavorable impact on OS in Asian patients (HR = 2.35, 95 % CI = 1.41–3.92). Moreover, up-regulation of HIF-1α was significantly associated with the depth of invasion (OR = 2.49, 95 % CI = 1.28–4.83), lymph node metastasis (OR = 2.15, 95 % CI = 1.27–3.66), and vascular invasion (OR = 2.23, 95 % CI = 1.20–4.14). HIF-1α expression might be a predicative factor of poor prognosis for gastric cancer particularly in Asia. 相似文献
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6.
Expression of GDNF and GDNFR-α mRNAs in Muscles of Patients with Motor Neuron Diseases 总被引:2,自引:0,他引:2
Masahiko Yamamoto Norimasa Mitsuma Akira Inukai Yasuhiro Ito Mei Li Terunori Mitsuma Gen Sobue 《Neurochemical research》1999,24(6):785-790
The mRNA expression levels of GDNF, GDNFR- and RET were examined in the muscles of amyotrophic lateral screlosis (ALS) and X-linked spinal and bulbar muscular atrophy (SBMA). GDNF mRNA levels were significantly elevated to variable extent in the diseased muscles compared to control muscles, although they were not specific to the type of the diseases. The diseased muscles also have a different expression pattern of GDNF mRNA isoforms from controls. GDNF mRNA expression, however, tended to reduce in advanced muscle pathology. On the other hand, GDNFR- mRNA levels were not changed significantly on expression levels in the diseased muscles. In situ hybridization study revealed that GDNF and GDNFR- mRNAs were localized in subsarcolemmal space of muscle cells. RET mRNA was not detected in control nor diseased muscles. These results suggest that the elevated muscle GDNF acts as a trophic signal for motor neurons of motor neuron diseases, implying a possible therapeutic implication of GDNF to this type of diseases.(Drs. Yamamoto, N. Mitsuma, Inukai, Ito, Li, Sobue) 相似文献
7.
Xaf1 can cooperate with TNFα in the induction of apoptosis, independently of interaction with XIAP 总被引:5,自引:0,他引:5
Xia Y Novak R Lewis J Duckett CS Phillips AC 《Molecular and cellular biochemistry》2006,286(1-2):67-76
XIAP-associated factor 1 (Xaf1) binds XIAP and re-localizes it to the nucleus, thus inhibiting XIAP activity and enhancing apoptosis [1]. Xaf1 expression is reduced or absent in tumor samples and cell lines suggesting it may function as a tumor suppressor [2–5]. To further study Xaf1 function we generated Xaf1 inducible cells in the osteosarcoma cell line Saos-2. Despite Xaf1 inducing apoptosis that is dramatically enhanced by TNFα we find no evidence for an interaction between Xaf1 and XIAP. Furthermore, Xaf1 expression sensitized XIAP−/− fibroblasts to TNFα, demonstrating the existence of a novel mechanism of Xaf1 induced apoptosis distinct from antagonizing XIAP. Xaf1 expression promotes cytochrome c release that cannot be blocked by inhibition of caspase activity. This implicates a role for the mitochondrial apoptotic pathway, consistent with the ability of Bcl2 to block Xaf1 induced apoptosis. The data indicate that in Saos2 cells Xaf1 activates the mitochondrial apoptotic pathway to facilitate cytochrome c release, thus amplifying apoptotic signals from death receptors. 相似文献
8.
Phase I study of recombinant human tumor necrosis factor α in advanced malignant disease 总被引:6,自引:0,他引:6
T. Moritz N. Niederle J. Baumann D. May E. Kurschel R. Osieka J. Kempeni E. Schlick C. G. Schmidt 《Cancer immunology, immunotherapy : CII》1989,29(2):144-150
Summary A phase I study with recombinant human tumor necrosis factor (rhuTNF-; Knoll AG, Ludwigshafen, FRG) in patients with advanced malignant disease was undertaken to evaluate drug toxicity (organ specifity, time course, predictability, reversibility, maximal tolerated dose), effectiveness, antigenicity and pharmacokinetics. TNF was administered as a test dose followed by daily i.v. infusions for 5 days, every 3 weeks (single i.v. infusion lasting 10 min, TNF dissolved in 50 ml 5% human albumin). Dosage was increased in groups of 3 or 4 patients from 0.04 mg/m2 to 0.28 mg/m2. A total of 19 patients with different cancers, including seven large-bowel carcinomas, three chronic myelogenous leukemias, three hypernephromas, two small-cell lung cancers, one malignant melanoma, one malignant lymphoma, one rhabdomyosarcoma and one fibrosarcoma were treated. Major side-effects were chills and fever (maximum 40.4°C, median 38.7°C, 19/19), headache (12/19), nausea and vomiting (12/19) and pronounced (>20%) hypotension (4/19). Acute side-effects could be diminished by paracetamol or indomethacin pretreatment, and with one possible exception no tachyphylaxis to TNF was noted. Mild renal toxicity was seen during TNF treatment. Pharmacokinetic studies showed a serum half-life (t
1/2) ranging from 11 min to 17 min for doses from 0.04 mg/m2 to 0.16 mg/m2 and prolonged clearance with t
1/2 ranging from 54 min to 70 min in the 0.20–0.28 mg/m2 dose range. No objective antitumor effects were observed in this phase I study. 相似文献
9.
Burkhard Hennemann Gabriele Beckmann Annette Eichelmann Annegret Rehm R. Andreesen 《Cancer immunology, immunotherapy : CII》1997,45(5):250-256
Cells of the monocyte/macrophage lineage have shown antitumor activity in vitro and in murine models after activation with
interferon (IFN) γ. In vitro data suggest an additional effect on macrophage antitumor activity when IFNγ is combined with
endotoxin (lipopolysaccharides; LPS). In this study we treated nine cancer patients with a total of 62 MAK infusion cycles
with autologous macrophages given intravenously (i.v.) after in vitro activation with IFNγ and LPS. Low-grade fever (WHO I/II)
was the commonest side-effect. Chills, nausea, and headache were noted when the number of transfused macrophages exceeded
2×108. One WHO IV toxicity occurred, consisting of hypotension after transfer of 3×108 cells, defining this dose as the maximum cell number tolerated. After pretreatment with ibuprofen, however, the maximum cell
number could be increased without reaching dose-limiting toxicity. The highest number of cells reinfused was 15×108. Circulating interleukin(IL)-6 increased in a dose-dependent manner as did IL-1 receptor antagonist (IL-1RA) and IL-8. Tumor
response consisted of one case of stable disease (12 weeks) in a patient with formerly progressing colorectal cancer and progressive
diseases in eight patients. This study indicates that reinfusion of autologous LPS-activated macrophages upon pretreatment
with ibuprofen is feasible and tolerated without major side-effects.
Received: 22 May 1997 / Accepted: 2 October 1997 相似文献
10.
Carlos Zamora-Atenza Cesar Diaz-Torne Carme Geli Cesar Diaz-Lopez M Angels Ortiz Patricia Moya Ivan Castellví Juan C Nieto Elisabet Cantó Jordi Casademont Candido Juarez Josep M Llobet Silvia Vidal 《Arthritis research & therapy》2014,16(4):R153
Introduction
Adalimumab is a fully human anti–tumor necrosis factor α (anti-TNFα) monoclonal antibody that specifically blocks the interaction of TNFα with its receptors. It binds both soluble and transmembrane TNFα. We hypothesized that blocking these TNFα signals regulates the altered TNFα production in rheumatoid arthritis (RA) patients.Methods
We compared, by flow cytometry, Toll-like receptor induction levels of membrane and intracellular TNFα in monocytes (iTNFα + CD14+ cells) from 12 patients before and after adalimumab treatment with those from 5 healthy donors.Results
Before starting the treatment, the percentage of iTNFα+ CD14+ cells in the RA patients was significantly lower than that in healthy donors (mean ± SEM = 33.16 ± 4.82% vs 66.51 ± 2.4%, P < 0.001). When we added in vitro TNFα to healthy donor culture cells, levels of iTNFα+ CD14+ cells decreased, suggesting that the TNFα signal was responsible for the iTNFα+ CD14+ cell downregulation observed in the RA patients. After 2, 6 and 12 adalimumab injections, we observed significant blocking of membrane and soluble TNFα and a progressive increase in iTNFα+ CD14+ cells in ten patients with a good to moderate response as defined by the European League Against Rheumatism (EULAR) criteria. Levels of iTNFα+ CD14+ cells after 12 injections in these 10 patients were comparable to levels in healthy donors. In two patients, iTNFα+ CD14+ cell upregulation was not observed, and their EULAR-defined responses had not improved. The first patient developed antiadalimumab antibodies, explaining why adalimumab was not able to block membrane and soluble TNFα. In the second patient, adalimumab was discontinued because of adverse effects, which led to a decrease in iTNFα+ CD14+ cells to levels measured before treatment.Conclusions
Our findings suggest that adalimumab treatment in RA patients can return iTNFα levels to those of healthy donors. This effect was not observed in the presence of neutralizing antiadalimumab antibodies. 相似文献11.
S. P. Richman J. U. Gutterman E. M. Hersh E. E. Ribi 《Cancer immunology, immunotherapy : CII》1978,5(1):41-44
Summary A vaccine composed of BCG cell wall skeleton (CWS) and a trehalose dimycolate called P3, attached to microdroplets of mineral oil, was evaluated for activity and toxicity when injected into tumor nodules. A total of 99 nodules in 23 patients with metastatic melanoma and carcinoma of the breast were treated overa dose range of 150 g, 300 g, and 600 g cell wall skeleton plus P3 per cm of nodule diameter. At least one injected nodule resolved in 11 of the 23 patients (48%), and 34% of all injected nodules resolved. Response correlated with nodule size of 1 cm or less, cutaneous location, and immunocompetence measured by PPD and recall skin testing. Toxicity became manifest in ulceration (61% of patients), fever (52%), and pain (26%). 相似文献
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13.
Uchida T Horiguchi S Tanaka Y Yamamoto H Kunii N Motohashi S Taniguchi M Nakayama T Okamoto Y 《Cancer immunology, immunotherapy : CII》2008,57(3):337-345
Background Human Vα24 natural killer T (NKT) cells are activated by the specific ligand, α-galactosylceramide (α-GalCer), in a CD1d-dependent
manner. Potent anti-tumor activity of activated NKT cells has been previously demonstrated.
Methods We conducted a phase I study with α-GalCer-pulsed antigen presenting cells (APCs) administered in the nasal submucosa of
patients with head and neck cancer, and evaluated the safety and feasibility of such a treatment. Nine patients with unresectable
or recurrent head and neck cancer received two treatments 1 week apart, of 1 × 108 of α-GalCer-pulsed autologous APCs into the nasal submucosa.
Results During the clinical study period, no serious adverse events (Common Terminology Criteria for Adverse Events version 3.0 greater
than grade 3) were observed. After the first and the second administration of α-GalCer-pulsed APCs, an increased number of
NKT cells was observed in four patients and enhanced natural killer activity was detected in the peripheral blood of eight
patients.
Conclusion The administration of α-GalCer-pulsed APCs into the nasal submucosa was found to be safe and induce anti-tumor activity in
some patients. 相似文献
14.
《生物化学与生物物理学报:疾病的分子基础》2020,1866(5):165660
Epidemiological studies over the last few decades have shown a strong influence of obesity on colon cancer risk and its progression. These studies have primarily focussed on the role of adipokines in driving cancer progression. We investigated the incidence of cancerous polyp formation and tumor progression in presence and absence of functional leptin along with exploring the role of tumor necrosis factor α (TNFα), under obese condition. By utilizing diet induced obese and genetically obese mice, carcinogen induced colon polyp formation was investigated. Experiments were performed using tumor tissues and cell lines to delineate the inter-relationship between leptin and TNFα. Data shown in this report indicates that in leptin knockdown obese mice, AOM/DSS induced polyps are smaller and lesser in numbers as compared to AOM/DSS induced polyps in diet induced obese mice. Further in vitro experiments suggest that abrogation of leptin associated pathways promote TNFα induced apoptosis. Mechanistically, we report that TNFα induces p53 independent cell death through up regulation of p53 upregulated modulator of apoptosis (PUMA). TNFα induced PUMA was inhibited upon pre- exposure of cells to leptin, prior to TNFα treatment. Collectively these results indicate that obesity due to leptin non-functionality facilitates TNFα induced colon cancer cell death. 相似文献
15.
Lisa Zimmer Julia Vaubel Peter Mohr Axel Hauschild Jochen Utikal Jan Simon Claus Garbe Rudolf Herbst Alexander Enk Eckhart K?mpgen Elisabeth Livingstone Leonie Bluhm Rainer Rompel Klaus G. Griewank Michael Fluck Bastian Schilling Dirk Schadendorf 《PloS one》2015,10(3)
Purpose
Up to 50% of patients with uveal melanoma (UM) develop metastatic disease with limited treatment options. The immunomodulating agent ipilimumab has shown an overall survival (OS) benefit in patients with cutaneous metastatic melanoma in two phase III trials. As patients with UM were excluded in these studies, the Dermatologic Cooperative Oncology Group (DeCOG) conducted a phase II to assess the efficacy and safety of ipilimumab in patients with metastatic UM.Patients and Methods
We undertook a multicenter phase II study in patients with different subtypes of metastatic melanoma. Here we present data on patients with metastatic UM (pretreated and treatment-naïve) who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs), including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC) v.4.0. Primary endpoint was the OS rate at 12 months.Results
Forty five pretreated (85%) and eight treatment-naïve (15%) patients received at least one dose of ipilimumab. 1-year and 2-year OS rates were 22% and 7%, respectively. Median OS was 6.8 months (95% CI 3.7–8.1), median progression-free survival 2.8 months (95% CI 2.5–2.9). The disease control rate at weeks 12 and 24 was 47% and 21%, respectively. Sixteen patients had stable disease (47%), none experienced partial or complete response. Treatment-related AEs were observed in 35 patients (66%), including 19 grade 3–4 events (36%). One drug-related death due to pancytopenia was observed.Conclusions
Ipilimumab has very limited clinical activity in patients with metastatic UM. Toxicity was manageable when treated as per protocol-specific guidelines.Trial Registration
ClinicalTrials.gov NCT01355120 相似文献16.
Pieter H. M. de Mulder Frans M. J. Debruyne Mart P. H. Franssen Arno D. H. Geboers Simon Strijk Ad G. M. Reintjes Wim H. Doesburg Otto Damsma 《Cancer immunology, immunotherapy : CII》1990,31(5):321-324
Summary In vitro studies have documented the synergistic antiviral and antiproliferative activity of recombinant interferon (rIFN) and rIFN. Furthermore, rIFN is a strong immunomodulator with optimal effects at a relative low dose (0.1 mg/m2). On the basis of these observations, we began a phase I/II study with the combination of rIFN at 100 µg/m2 (2 × 106 IU/m2) and rIFN2c 6 µg/m2 (2 × 106 IU/m2), injected twice a week subcutaneously. In cases of stable or progressive disease we increased the dose of rIFN2c every 2 weeks by 6 µg/m2 until the maximum tolerated dose was reached. A total of 32 patients with proven progressive renal-cell carcinoma were included. Of the 31 eligible patients, 21 were male and 10 female, their average age was 57.2 years (range 35–72), 28 had had nephrectomy, their median Karnofsky performance status was 90% (70%–100%), and their tumors were localized predominantly to visceral tissue. In 2, response was complete and in 6 it was partial, for a response rate of 25%. The disease had stabilized in 5 patients and progressed in 16. The median duration of partial response was 14 months (8–16 months); of 2 cases of complete response, 1 persists (23+ months), and the other suffered a relapse after 22 months. The median time to response was 24 weeks (18–24 weeks). The maximum tolerated dose of rIFN was 30 µg/m2 (range of 6–36 µg/m2). Side-effects included those known to be associated with interferon treatment. One patient developed septicemia during a period with grade 4 leukopenia. Our study permits no conclusion regarding the additional value of rIFN. 相似文献
17.
Kobayashi H Tanaka Y Yagi J Minato N Tanabe K 《Cancer immunology, immunotherapy : CII》2011,60(8):1075-1084
Human Vγ2 Vδ2-bearing T cells have recently received much attention in cancer immunotherapy. In this study, we conducted a
phase I/II clinical trial of the adoptive transfer of γδ T cells to patients with advanced renal cell carcinoma. Eleven patients
who had undergone nephrectomy and had lung metastasis were enrolled. Peripheral blood γδ T cells obtained from the patients
were stimulated ex vivo with 2-methyl-3-butenyl-1-pyrophosphate (2M3B1PP), a synthetic pyrophosphomonoester antigen, and transferred
in combination with zoledronic acid (Zol) and teceleukin (recombinant human interleukin-2). Expanded γδ T cells exhibited
potent cytotoxic activity against tumor cells in vitro, and the proportion of peripheral blood γδ T cells among CD3+ cells typically peaked three to 5 days after transfer. Tumor doubling time was prolonged in all 11 patients, and the best
overall responses were 1 CR, 5 SD, and 5 PD, as defined based on Response Evaluation Criteria in Solid Tumors (RECIST). Although
ten patients developed adverse reactions of grade ≥3, they were likely to have been the result of the concomitant infusion
of Zol and IL-2, and most symptoms swiftly reverted to normal during the course of treatment. In conclusion, this clinical
trial demonstrated that our regimen for the adoptive transfer of γδ T cells in combination with Zol and IL-2 was well tolerated
and that objective clinical responses could be achieved in some patients with advanced renal cell carcinoma. 相似文献
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19.
Rongying Zhu Xiang Xue Mingjing Shen Ying Tsai Peter C. Keng Yongbing Chen Soo Ok Lee Yuhchyau Chen 《Experimental cell research》2019,374(1):181-188
Cisplatin-resistant (A549CisR and H292CisR) and radioresistant (A549R26 and H292R22) sub-line non-small cell lung cancer (NSCLC) cells were developed in our lab by long term treatment of parental cells with cisplatin or radiation. Our data showed no cross-resistance between these two sets of cell lines, indicating that molecular mechanisms of developing each resistance may be different. Using these sub-line cells, we sought to reveal the most significantly up-regulated molecules in cisplatin-resistant and radioresistant lung cancer cells, compared with parental cells. In qPCR analyses of screening DNA repair and cell survival-associated molecules, we identified NFκB and TNFα as the most significantly up-regulated molecules in cisplatin-resistant and radioresistant lung cancer cells, respectively, compared with parental cells. Western blot analysis of parental vs. resistant cells and the IHC staining of tumor tissues of A549P, A549CisR, and A549R26 cell-derived xenografts in mice confirmed such results. Next, studies using specific inhibitors of NFκB and TNFα and experiments using NFκB and TNFα-knocked down cells showed that inhibition or knockdown of NFκB overcame cisplatin-resistance, while inhibition or knockdown of TNFα increased radiosensitivity of radioresistant lung cancer cells. Therefore, these two molecules may be used as markers of the prognosis/diagnosis of individual resistance development during lung cancer treatment. 相似文献
20.
Kensaku Aihara Tomohiro Handa Toru Oga Kizuku Watanabe Kiminobu Tanizawa Kohei Ikezoe Yoshio Taguchi Hiroe Sato Kazuo Chin Sonoko Nagai Shuh Narumiya Athol U. Wells Michiaki Mishima 《PloS one》2013,8(6)