Search tips
Search criteria

Results 1-14 (14)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  The effect of tumor volume and its change on survival in stage III non-small cell lung cancer treated with definitive concurrent chemoradiotherapy 
To investigate a prognostic role of gross tumor volume (GTV) changes on survival outcomes following concurrent chemoradiotherapy (CCRT) in stage III non-small-cell lung cancer (NSCLC) patients.
We enrolled 191 patients with stage III NSCLC from 2001 to 2009 undergoing definitive CCRT. The GTV of 157 patients was delineated at the planning CT prior to CCRT and with a follow-up CT 1 month after CCRT. We assessed the volumetric parameters of pre-treatment GTV (GTVpre) post-treatment GTV (GTVpost), and volume reduction ratio of GTV (VRR). The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and locoregional progression-free survival (LRPFS). The best cut-off value was defined as that which exhibited the maximum difference between the two groups.
The median follow-up duration was 52.7 months in surviving patients. Median survival, 3-year OS, PFS and LRPFS rates were 25.5 months, 36.4%, 23.0%, and 45.0%, respectively. The selected cut-off values were 50 cm3 for GTVpre, 20 cm3 for GTVpost, and 50% for VRR. The smaller GTVpre and GTVpost values were associated with better OS (p < 0.001 and p = 0.015) and PFS (p = 0.001 and p = 0.004), respectively, upon univariate analysis. The higher VRR of > 50% was associated with a trend toward poorer OS (p = 0.004) and PFS (p = 0.054). Upon multivariate analysis, smaller GTVpre indicated significantly improved OS (p = 0.001), PFS (p = 0.013) and LRPFS (p = 0.002), while smaller GTVpost was marginally significant for PFS (p = 0.086). Higher VRR was associated with a trend toward poorer OS (p = 0.075).
In patients with stage III NSCLC undergoing definitive CCRT, GTVpre was an independent prognostic factor of survival. Notably, improved outcome was not correlated with higher VRR after short-term follow-up with CT alone.
Electronic supplementary material
The online version of this article (doi:10.1186/s13014-014-0283-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4268851  PMID: 25498887
Concurrent chemoradiotherapy; Gross tumor volume; Locoregional control; Non-small-cell lung cancer; Survival
2.  Risk Factors for Distant Metastasis as a Primary Site of Treatment Failure in Early-Stage Breast Cancer 
Chonnam Medical Journal  2014;50(3):96-101.
The aim of this study was to evaluate the risk factors for distant metastasis (DM) as a primary site of failure in early-stage breast cancer. Data from 294 patients diagnosed with pathologic stage I or II breast cancer between January 2000 and December 2005 were reviewed retrospectively. Median follow-up duration was 81.0 months (range, 18-135 months). The total number of patients with DM without evidence of locoregional recurrence was 20 and the median time between surgery and DM was 29 months (range, 9-79 months). Median survival time was 38 months (range, 22-77 months) after operation. HER-2 positivity (p=0.015), T stage of tumor (p=0.012), and number of involved lymph nodes (p=0.008) were significant predictors of DM in the univariable analysis. Number of involved lymph nodes [p=0.005, hazards ratio (HR): 1.741; 95% confidence interval (CI): 1.178-2.574] and HER-2 positivity (p=0.018, HR: 2.888; 95% CI: 1.201-6.941) had a statistically significant effect on DM-free survival in the multivariable analysis. A cautious evaluation may be helpful when patients with risk factors for DM have symptoms implying the possibility of DM. To reduce DM, applying intensive therapy is needed after curative surgery for patients with high risk for DM.
PMCID: PMC4276798  PMID: 25568845
Breast neoplasm; Neoplasm metastasis; Risk factors
3.  Effects of Atrial Fibrillation on the Outcome of the Rehabilitation in Patients With Cerebral Infarction 
Annals of Rehabilitation Medicine  2014;38(6):766-774.
To evaluate the influence of atrial fibrillation (Af) on the clinical characteristics and rehabilitation outcomes of patients with cerebral infarction.
We evaluated 87 of 101 consecutive patients with cerebral infarction admitted to the department of physical medicine and rehabilitation during their rehabilitation period. The patients were divided into two groups, Af and non-Af groups. We estimated characteristics of patient demographic features, disease duration, length of hospital stay, other comorbidities and risk factors for stroke, and functional status at admission and at discharge and compared those in patients with and without Af. Functional Independence Measure (FIM), the Modified Barthel Index (MBI), and the PULSES profile (PULSES) were used to evaluate functional status.
The number in the Af group was 20 (22.9%) and that of the non-Af group was 67 (77.1%). Demographic features, other comorbidities, motor function, cognitive function, neurological scales, and brain lesions did not differ significantly between the groups. The incidence of coronary artery disease and valvular heart disease were significantly correlated with the incidence of Af in multivariate analysis. Based on FIM, MBI, and PULSES scores, functional improvement in the Af group after rehabilitation was significantly less than that of the non-Af group.
Af was shown to be associated with a markedly negative result in rehabilitation in patients with cerebral infarction. Thus, early recognition and proper treatment of Af may help patients achieve more effective rehabilitation.
PMCID: PMC4280372  PMID: 25566475
Atrial fibrillation; Cerebral infarction; Rehabilitation outcomes
4.  Conventional papillary thyroid carcinoma: effects of cystic changes visible on ultrasonography on disease prognosis 
Ultrasonography  2014;33(4):291-297.
To investigate the characteristics of papillary thyroid carcinoma (PTC) with cystic changes visible on ultrasonography (US).
This study included 553 PTCs in 553 patients between January 2003 and August 2004. One radiologist with 10 years of experience in thyroid imaging retrospectively reviewed the preoperative US images. Two different groups were formed according to two different reference points (group 1, 25%; group 2, 50%) of the cystic component. Patients between the groups were compared according to their clinicopathologic characteristics. Disease-free survival (DFS) was estimated. Cox’s multivariate proportional hazards regression model was used to identify the effect of variable factors on the recurrence risk.
Fifty-six patients (10.1%) were confirmed to have tumor recurrence within the follow-up period. Thirty-five patients had regional metastasis, one had distant metastasis, eight had multiple site metastases, and 12 had biochemical recurrence. PTC patients with a ≤ 50% or PTC patients with a ≤ 25% cystic component did not have a statistically significant longer DFS than those with a >50% (hazard ratio [HR], 1.118; 95% confidence interval [CI], 0.255 to 4.910; P=0.883) or those with a >25% cystic component (HR, 0.569; 95% CI, 0.164 to 1.976; P=0.375), respectively. Moreover, independent predictors of recurrence were pathologic size, male gender, and lymph node metastasis, not a >50% or >25% cystic component.
The proportion of the cystic component in PTCs did not affect DFS.
PMCID: PMC4176114  PMID: 25212970
Thyroid nodule; Ultrasonography; Thyroid neoplasms
5.  Dose-Related Effect of Extracorporeal Shock Wave Therapy for Plantar Fasciitis 
Annals of Rehabilitation Medicine  2013;37(3):379-388.
To examine the dose-related effect of extracorporeal shock wave therapy (ESWT) for plantar fasciitis.
Sixty patients with plantar fasciitis despite conservative treatment were enrolled. The patients were divided into a low-energy group (group L: n=30, 1,000 shocks/session, energy flux density [EFD] per shock 0.08 mJ/mm2) and a medium-energy group (group M: n=30, 1,000 shocks/session, EFD 0.16 mJ/mm2). The main outcome measures were visual analogue scale (VAS), Roles and Maudsley (RM) score, and thickness of plantar fascia (PF). To compare the effects between each group, follow-up was carried out 1 week after 3 and 6 sessions, and 1 and 3 months after ESWT.
Significant VAS and RM score improvement, and PF thickness reduction were observed in both groups (p<0.01). After 3 sessions of ESWT, group M showed significant improvement in the VAS and RM score than group L, whereas after 3 additional sessions applied in group L, the main outcomes were no longer significantly different in both groups (p>0.05).
Therapeutic effect might disclose a dose-related relationship; therefore, EFD and the times of the session are considerable factors when treating with ESWT.
PMCID: PMC3713295  PMID: 23869336
Plantar fasciitis; Extracorporeal shock wave therapy; Dose-related Effect
6.  Treatment outcome in patients with triple negative early stage breast cancers compared with other molecular subtypes 
Radiation Oncology Journal  2012;30(3):124-131.
To determine whether triple negative (TN) early stage breast cancers have poorer survival rates compared with other molecular types.
Materials and Methods
Between August 2000 and July 2006, patients diagnosed with stage I, II early stage breast cancers, in whom all three markers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor [HER]-2) were available and treated with modified radical mastectomy or breast conserving surgery followed by radiotherapy, were retrospectively reviewed.
Of 446 patients, 94 (21.1%) were classified as TN, 57 (12.8%) as HER-2 type, and 295 (66.1%) as luminal. TN was more frequently associated with young patients younger than 35 years old (p = 0.002), higher histologic grade (p < 0.0001), and nuclear (p < 0.0001). The median follow-up period was 78 months (range, 4 to 130 months). There were 9 local relapses (2.0%), 15 nodal (3.4%), 40 distant metastases (9.0%), and 33 deaths (7.4%) for all patients. The rates of 5-year OS, DFS, LFS, and DMFS for all patients were 95.5%, 89.9%, 95.4%, and 91.7%, respectively. There were no significant differences in OS, DFS, LFS, and DMFS between triple negative and other subtypes (p > 0.05).
We found that patients with TN early stage breast cancers had no difference in survival rates compared with other molecular subtypes. Prospective study in homogeneous treatment group will need for a prognosis of TN early stage breast cancer.
PMCID: PMC3496846  PMID: 23170291
Triple negative breast cancer; Early stage; Overall survival; Disease-free survival; Locoregional relapse-free survival; Distant metastasis-free survival
7.  The Effect of Bedside Exercise Program on Stroke Patients with Dysphagia 
Annals of Rehabilitation Medicine  2012;36(4):512-520.
To examine the effects of a bedside exercise program on the recovery of swallowing after a stroke.
Fifty stroke patients with dysphagia (<6 months post-stroke) were enrolled and classified into two groups, the experimental (25 subjects) and control groups (25 subjects). The control group was treated with conventional swallowing therapy. The experimental group received additional bedside exercise training, which consisted of oral, pharyngeal, laryngeal, and respiratory exercises, 1 hour per day for 2 months, and they were instructed regarding this program through the nursing intervention. All patients were assessed for their swallowing function by Videofluoroscopic Swallowing Study (VFSS), using the New VFSS scale, the level of functional oral intake, the frequency of dysphagia complications, the presence (or not) of tube feeding, the mood state and quality of life before the treatment and at 2 months after the treatment.
After 2 months of treatment, the experimental group showed a significant improvement in the swallowing function at the oral phase in the New VFSS Scale than that of the control group (p<0.05). Further, they also showed less depressive mood and better quality of life than the control group. However, there was no significant change in the incidence of dysphagia complication and the presence (or not) of tube feeding between the two groups.
Bedside exercise program showed an improvement of swallowing function and exhibited a positive secondary effect, such as mood state and quality of life, on subacute stroke patients with dysphagia. For improvement of rehabilitation results on subacute stroke patients with dysphagia, this study suggests that additional intensive bedside exercise would be necessary.
PMCID: PMC3438418  PMID: 22977777
Dysphagia; Videofluoroscopic swallowing study; Bedside exercise
8.  The Effect of The Forward Head Posture on Postural Balance in Long Time Computer Based Worker 
To estimate the effects of a relatively protruded head and neck posture on postural balance, in computer based worker.
Thirty participants, who work with computers for over 6 hrs per day (Group I), and thirty participants, who rarely work with computers (Group II), were enrolled. The head and neck posture was measured by estimating angles A and B. A being the angle between the tragus of the ear, the lateral canthus of the eye, and horizontal line and B the angle between the C7 spinous process, the tragus of the ear, and the horizontal line. The severity of head protrusion with neck extension was assessed by the subtraction of angle A from angle B. We also measured the center of gravity (COG) and postural balance by using computerized dynamic posturography to determine the effect of computer-based work on postural balance.
Results indicated that group I had a relatively more protruded head with extensive neck posture (angle B-A of group I and group II, 28.2±8.3, 32.9±6.0; p<.05). The COG of group I tended more toward the anterior than that of group II. Postural imbalance and impaired ability to regulate movement in forward and backward direction were also found.
The results of this study suggest that forward head postures during computer-based work may contribute to some disturbance in the balance of healthy adults. These results could be applied to education programs regarding correct postures when working at a computer for extended periods of time.
PMCID: PMC3309315  PMID: 22506241
Turtle neck; Center of gravity; Postural balance
9.  A comparison of preplan MRI and preplan CT-based prostate volume with intraoperative ultrasound-based prostate volume in real-time permanent brachytherapy 
Radiation Oncology Journal  2011;29(3):199-205.
The present study compared the difference between intraoperative transrectal ultrasound (iTRUS)-based prostate volume and preplan computed tomography (CT), preplan magnetic resonance imaging (MRI)-based prostate volume to estimate the number of seeds needed for appropriate dose coverage in permanent brachytherapy for prostate cancer.
Materials and Methods
Between March 2007 and March 2011, among 112 patients who underwent permanent brachytherapy with 125I, 60 image scans of 56 patients who underwent preplan CT (pCT) or preplan MRI (pMRI) within 2 months before brachytherapy were retrospectively reviewed. Twenty-four cases among 30 cases with pCT and 26 cases among 30 cases with pMRI received neoadjuvant hormone therapy (NHT). In 34 cases, NHT started after acquisition of preplan image. The median duration of NHT after preplan image acquisition was 17 and 21 days for cases with pCT and pMRI, respectively. The prostate volume calculated by different modalities was compared. And retrospective planning with iTRUS image was performed to estimate the number of 125I seed required to obtain recommended dose distribution according to prostate volume.
The mean difference in prostate volume was 9.05 mL between the pCT and iTRUS and 6.84 mL between the pMRI and iTRUS. The prostate volume was roughly overestimated by 1.36 times with pCT and by 1.33 times with pMRI. For 34 cases which received NHT after image acquisition, the prostate volume was roughly overestimated by 1.45 times with pCT and by 1.37 times with pMRI. A statistically significant difference was found between preplan image-based volume and iTRUS-based volume (p < 0.001). The median number of wasted seeds is approximately 13, when the pCT or pMRI volume was accepted without modification to assess the required number of seeds for brachytherapy.
pCT-based volume and pMRI-based volume tended to overestimate prostate volume in comparison to iTRUS-based volume. To reduce wasted seeds and cost of the brachytherapy, we should take the volume discrepancy into account when we estimate the number of 125I seeds for permanent brachytherapy.
PMCID: PMC3429903  PMID: 22984671
Brachytherapy; Prostate cancer; Prostate volume
10.  Evolutionarily Conserved Role of Calcineurin in Phosphodegron-Dependent Degradation of Phosphodiesterase 4D▿  
Molecular and Cellular Biology  2010;30(18):4379-4390.
Calcineurin is a widely expressed and highly conserved Ser/Thr phosphatase. Calcineurin is inhibited by the immunosuppressant drug cyclosporine A (CsA) or tacrolimus (FK506). The critical role of CsA/FK506 as an immunosuppressant following transplantation surgery provides a strong incentive to understand the phosphatase calcineurin. Here we uncover a novel regulatory pathway for cyclic AMP (cAMP) signaling by the phosphatase calcineurin which is also evolutionarily conserved in Caenorhabditis elegans. We found that calcineurin binds directly to and inhibits the proteosomal degradation of cAMP-hydrolyzing phosphodiesterase 4D (PDE4D). We show that ubiquitin conjugation and proteosomal degradation of PDE4D are controlled by a cullin 1-containing E3 ubiquitin ligase complex upon dual phosphorylation by casein kinase 1 (CK1) and glycogen synthase kinase 3β (GSK3β) in a phosphodegron motif. Our findings identify a novel signaling process governing G-protein-coupled cAMP signal transduction—opposing actions of the phosphatase calcineurin and the CK1/GSK3β protein kinases on the phosphodegron-dependent degradation of PDE4D. This novel signaling system also provides unique functional insights into the complications elicited by CsA in transplant patients.
PMCID: PMC2937537  PMID: 20647544
11.  Systemic Fate of the Adipocyte-Derived Factor Adiponectin 
Diabetes  2009;58(9):1961-1970.
The adipocyte-derived secretory protein adiponectin has been widely studied and shown to have potent insulin-sensitizing, antiapoptotic, and anti-inflammatory properties. While its biosynthesis is well understood, its fate, once in circulation, is less well established.
Here, we examine the half-life of adiponectin in circulation by tracking fluorescently labeled recombinant adiponectin in the circulation, following it to its final destination in the hepatocyte.
Despite its abundant presence in plasma, adiponectin is cleared rapidly with a half-life of ∼75 min. A more bioactive version carrying a mutation at cysteine 39 is cleared within minutes. Even though steady-state levels of adiponectin differ between male and female mice, we failed to detect any differences in clearance rates, suggesting that differences in plasma are mostly due to differential production rates. In a metabolically challenged state (high-fat diet exposure or in an ob/ob background), adiponectin levels are reduced in plasma and clearance is significantly prolonged, reflecting a dramatic drop in adiponectin production levels.
Combined, these results show a surprisingly rapid turnover of adiponectin with multiple fat pads contributing to the plasma levels of adiponectin and clearance mediated primarily by the liver. It is surprising that despite high-level production and rapid clearance, plasma levels of adiponectin remain remarkably constant.
PMCID: PMC2731534  PMID: 19581422
12.  Obesity-associated improvements in metabolic profile through expansion of adipose tissue 
The Journal of Clinical Investigation  2007;117(9):2621-2637.
Excess caloric intake can lead to insulin resistance. The underlying reasons are complex but likely related to ectopic lipid deposition in nonadipose tissue. We hypothesized that the inability to appropriately expand subcutaneous adipose tissue may be an underlying reason for insulin resistance and β cell failure. Mice lacking leptin while overexpressing adiponectin showed normalized glucose and insulin levels and dramatically improved glucose as well as positively affected serum triglyceride levels. Therefore, modestly increasing the levels of circulating full-length adiponectin completely rescued the diabetic phenotype in ob/ob mice. They displayed increased expression of PPARγ target genes and a reduction in macrophage infiltration in adipose tissue and systemic inflammation. As a result, the transgenic mice were morbidly obese, with significantly higher levels of adipose tissue than their ob/ob littermates, leading to an interesting dichotomy of increased fat mass associated with improvement in insulin sensitivity. Based on these data, we propose that adiponectin acts as a peripheral “starvation” signal promoting the storage of triglycerides preferentially in adipose tissue. As a consequence, reduced triglyceride levels in the liver and muscle convey improved systemic insulin sensitivity. These mice therefore represent what we believe is a novel model of morbid obesity associated with an improved metabolic profile.
PMCID: PMC1950456  PMID: 17717599
13.  Secretion of the Adipocyte-Specific Secretory Protein Adiponectin Critically Depends on Thiol-Mediated Protein Retention▿ †  
Molecular and Cellular Biology  2007;27(10):3716-3731.
Adiponectin is a secretory protein abundantly secreted from adipocytes. It assembles into a number of different higher-order complexes. Adipocytes maintain tight control over circulating plasma levels, suggesting the existence of a complex, highly regulated biosynthetic pathway. However, the critical mediators of adiponectin maturation within the secretory pathway have not been elucidated. Previously, we found that a significant portion of de novo-synthesized adiponectin is not secreted and retained in adipocytes. Here, we show that there is an abundant pool of properly folded adiponectin in the secretory pathway that is retained through thiol-mediated retention, as judged by the release of adiponectin in response to treatment of adipocytes with reducing agents. Adiponectin is covalently bound to the ER chaperone ERp44. An adiponectin mutant lacking cysteine 39 fails to stably interact with ERp44, demonstrating that this residue is the primary site mediating the covalent interaction. Another ER chaperone, Ero1-Lα, plays a critical role in the release of adiponectin from ERp44. Levels of both of these proteins are highly regulated in adipocytes and are influenced by the metabolic state of the cell. While less critical for the secretion of trimers, these chaperones play a major role in the assembly of higher-order adiponectin complexes. Our data highlight the importance of posttranslational events controlling adiponectin levels and the release of adiponectin from adipocytes. One mechanism for increasing circulating levels of specific adiponectin complexes by peroxisome proliferator-activated receptor gamma agonists may be selective upregulation of rate-limiting chaperones.
PMCID: PMC1899995  PMID: 17353260
14.  Role of Transcription Factor NFAT in Glucose and Insulin Homeostasis▿  
Molecular and Cellular Biology  2006;26(20):7372-7387.
Compromised immunoregulation contributes to obesity and complications in metabolic pathogenesis. Here, we demonstrate that the nuclear factor of activated T cell (NFAT) group of transcription factors contributes to glucose and insulin homeostasis. Expression of two members of the NFAT family (NFATc2 and NFATc4) is induced upon adipogenesis and in obese mice. Mice with the Nfatc2−/− Nfatc4−/− compound disruption exhibit defects in fat accumulation and are lean. Nfatc2−/− Nfatc4−/− mice are also protected from diet-induced obesity. Ablation of NFATc2 and NFATc4 increases insulin sensitivity, in part, by sustained activation of the insulin signaling pathway. Nfatc2−/− Nfatc4−/− mice also exhibit an altered adipokine profile, with reduced resistin and leptin levels. Mechanistically, NFAT is recruited to the transcription loci and regulates resistin gene expression upon insulin stimulation. Together, these results establish a role for NFAT in glucose/insulin homeostasis and expand the repertoire of NFAT function to metabolic pathogenesis and adipokine gene transcription.
PMCID: PMC1636854  PMID: 16908540

Results 1-14 (14)