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Favorable Outcome in Elderly Asian Patients with Metastatic Renal Cell Carcinoma Treated with Everolimus: The Osaka Urologic Oncology Group

  • Inamoto, Teruo;Azuma, Haruhito;Nonomura, Norio;Nakatani, Tatsuya;Matsuda, Tadashi;Nozawa, Masahiro;Ueda, Takeshi;Kinoshita, Hidefumi;Nishimura, Kazuo;Kanayama, Hiro-Omi;Miki, Tsuneharu;Tomita, Yoshihiko;Yoshioka, Toshiaki;Tsujihata, Masao;Uemura, Hirotsugu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1811-1815
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    • 2014
  • Background: In clinical trials with no upper age limit, the proportion of older patients is usually small, probably reflecting the more conservative approach adopted by clinicians when treating the elderly. An exploratory analysis of elderly patients in the RECORD-1 Trial showed that patients ${\geq}$ 65 y.o. had superior median PFS than overall RECORD-1 population (5.4 months and 4.9 months, respectively). We investigated the efficacy, relative benefit and safety of Everolimus (EVE) as sequential therapy after failure of VEGFr-TKI therapy for older patients with metastatic renal cell cancer (mRCC), in daily practice. Materials and Methods: 172 consecutive IRB approved patients with mRCC (median age 65, M:F 135/37, 78% clear cell) who received salvage EVE at 39 tertiary institutions between October 2009 and August 2011 were included in this analysis. Some 31% had progressed on sunitinib, 22% on sorafenib, 1% on axitinib, 41% on sequential therapy, and 5% had received other therapy. Patients with brain metastases were not included and 95% of the patients had a ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1. Previous radiotherapy was an exclusion criterion, but prior chemotherapy was permitted. Adequate organ function and hematologic parameters were mandatory. EVE administration was approved by the institutional review board at each participating institution and signed informed consent was obtained from all patients. Results: Median time of the whole cohort to last follow-up was 3.5 months (range 0.4-15.2 months). Forty four percent were continuing to take EVE at last followup. There were 86 (50%) patients ${\geq}$ 65 y.o. and 86 (50%) <65 y.o. The percentage of patients who showed PR/SD was higher in the older group than in the younger one (5.9%/61.2% vs 1.2%/46.5%, respectively). Median survival of older patients was also significantly longer (3.5 +/- 0.31 vs 3.1 +/- 0.34, hazard ratio=0.45, CI; 0.255-0.802). Analysis using Cox regression model adjusted for gender, PS, number of metastases, site of metastases, histology, smoking history and age detected an association between age and PFS (p=0.011). The frequency of adverse events in elderly patients treated with EVE was no greater than that in younger patients, although such toxicity may have had a greater impact on their quality of life. Conclusions: Older patients should not generally be excluded from accepted therapies (mTOR inhibitors after failure of VEGFr-TKI therapy) for mRCC.

Protection of UV-derived Skin Cell Damage and Anti-irritation Effect of Juniperus chinensis Xylem Extract (향나무추출물의 광손상으로부터 피부세포 보호와 자극완화 효과에 대한 연구)

  • 김진화;박성민;심관섭;이범천;표형배
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.30 no.1
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    • pp.63-71
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    • 2004
  • The human skin is constantly exposed to environmental irritants such as ultraviolet, smoke, chemicals. Free radicals and reactive oxygen species (ROS) caused by these environmental facts play critical roles in cellular damage. These irritants are in themselves damaging to the skin structure but they also participate the immensely complex inflammatory reaction. The purpose of this study was to investigate the skin cell protective effect of Juniperus chinensis xylem extract on the UV and SLS-induced skin cell damages. We tested free radical and superoxide scavenging effect in vitro. We found that Juniperus chinensis xylem extracts had potent radical scavenging effect by 98% at 100 $\mu\textrm{g}$/mL. Fluorometric assays of the proteolytic activities of matrix metalloproteinase-l(MMP-1, collagenase) were performed using fluorescent collagen substrates. UV A induced MMP-1 synthesis and activity were analyzed by enzyme-linked immunosorbent assay (ELISA) and gelatin-based zymography in skin fibroblasts. The extract of Juniperus chinensis showed strong inhibitory effect on MMP-1 activities by 97% at 100 $\mu\textrm{g}$/mL and suppressed the UVA induced expression of MMP-1 by 79% at 25 $\mu\textrm{g}$/mL. This extract also showed strong inhibition on MMP-2 activity in UVA irradiated fibroblast by zymography. We also examined anti-inflammatory effects by the determination test of proinflammatory cytokine, interleukin 6 in HaCaT keratinocytes. In this test Juniperus chinensis decreased expression of interleukin 6 about 30%. Expression of prostaglandin E$_2$, (PGE$_2$) after UVB irradiation was measured by competitive enzyme immunoassay (EIA) using PGE$_2$ monoclonal antibody. At the concentrations of 5-50 $\mu\textrm{g}$/mL of the extracts, the production of PGE$_2$ by HaCaT keratinocytes (24 hours after 10 mJ/$\textrm{cm}^2$ UVB irradiation) was significantly inhibited in culture supernatants (p〈0.05). The viability of cultured HaCaT keratinocytes was significantly reduced at the doses of above 10 mJ/$\textrm{cm}^2$ of UVB irradiation, but the presence of these extracts improved cell viability comparing to control after UVB irradiation. We also investigated the protective effect of this extract in sodium lauryl sulfate (SLS)-induced irritant skin reactions from 24 hour exposure. Twice a day application of the extract for reducing local inflammation in human skin was done. Irritant reactions were assessed by various aspects of skin condition, that is, erythema (skin color reflectance) and transepidermal water loss (TEWL). After 5 days the extract was found to reduce SLS-induced skin erythema and improve barrier regeneration when compared to untreated symmetrical test site. In conclusion, our results suggest that Juniperus chinensis can be effectively used for the prevention of UV and SLS-induced adverse skin reactions such as radical production, inflammation and skin cell damage.

Spontaneous Resolution Rate and Predictive Factors of Resolution in Children with Primary Vesicoureteral Reflux (소아에서 일차성 방광요관역류의 자연소실율 및 관련 인자)

  • Kang, Eun-Young;Kim, Min-Sun;Kwon, Keun-Sang;Park, Eun-Hye;Lee, Dae-Yeol
    • Childhood Kidney Diseases
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    • v.11 no.1
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    • pp.74-82
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    • 2007
  • Purpose : To analyze the clinical characteristics, spontaneous resolution rate and predictive factors of resolution in children with primary vesicoureteral reflux(VUR). Methods : Between October 1991 and July 2003, 149 children diagnosed with primary VUR at Chonbuk National University Hospital were reviewed retrospectively. All of the patients were maintained on low-dose antibiotic prophylaxis and underwent radionuclide cystograms at 1 year intervals over 3 years after the initial diagnosis of VUR by voiding cystourethrogram was made. Results : The median time to resolution of VUR was 24 months and the total 3 year-cumulative resolution rate of VUR was 61.7%. The following variables were associated with resolution of VUR according to univariate analysis-; age<1 year, male gender, mild grade of reflux, unilateral reflux, congenital hydronephrosis as clinical presentation at time of diagnosis of VUR, absence of focal defects in the renal scan at diagnosis, absence of recurrent UTI, renal scars and small kidney during follow-up. After adjustment by Cox regression model, five variables remained as independent predictors of VUR resolution; age<1 yew, relative risk 1.77(P<0.05), VUR grade I+II 2.98(P<0.05), absence of renal scars 2.23(P<0.05), and absence of small kidney 5.20(P<0.01) during follow-up. Conclusion : In this study, spontaneous resolution rate of VUR, even high grade reflux, is high in infants during medical management, and it was related to age, reflux grade at diagnosis, absence of renal scars and small kidney during follow-up. Therefore early surgical intervention should be avoided and reserved for the selected groups.

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A Numerical Study of Hydraulic Fractures Propagation with Rock Bridges (Rock bridges를 고려한 수치 해석적 수압파쇄 균열거동 연구)

  • 최성웅
    • Tunnel and Underground Space
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    • v.10 no.3
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    • pp.447-456
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    • 2000
  • Rock bridge in rock masses can be considered as one of several types of opening-mode fractures, and also it has been known to have a great influence on the stability of structures in rock mass. In the beginning of researching a rock bridge it used to be studied only in characteristics of its behavior, as considering resistance of material itself. However the distribution pattern of rock bridges, which can affect the stability of rock structures, is currently researched with a fracture mechanical approach in numerical studies. For investigating the effect of rock bridges on the development pattern of hydraulic fractures, the author analyzed numerically the stress state transition in rock bridges and their phenomena with a different pattern of the rock bridge distributions. From the numerical studies, a two-crack configuration could be defined to be representative of the most critical conditions for rock bridges, only when cracks are systematic and same in their length and angle. Moreover, coalescence stresses and onset of propagation stresses could be known to increase with decreasing s/L ratio or increasing d/L ratio. The effect of pre-existing crack on hydraulic fracturing was studied also in numerical models. Different to the simple hydraulic fracturing modeling in which the fractures propagated exactly parallel to the maximum remote stress, the hydraulic fractures with pre-existing cracks did not propagate parallel to the maximum remote stress direction. These are representative of the tendency to change the hydraulic fractures direction because of the existence of pre-existing crack. Therefore s/L, d/L ratios will be identical as a function effective on hydraulic fractures propagation, that is, the K$_1$ value increase with decreasing s/L ratio or increasing d/L ratio and its magnification from onset to propagation increases with decreasing s/L ratio. The scanline is a commonly used method to estimate the fracture distribution on outcrops. The data obtained from the scanline method can be applied to the evaluation of stress field in rock mass.

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The Prognostic Factors Affecting Survival in Muscle Invasive Bladder Cancer Treated with Radiotherapy (방사선치료를 받은 근 침윤성 방광암의 예후 인자)

  • Chung Woong-Ki;Oh Bong-Ryoul;Ahn Sung Ja;Nah Byung Sik;Kwon Dong-Deuk;Park Kwangsung;Ryu Soo-Bang;Park Yang-IL
    • Radiation Oncology Journal
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    • v.20 no.2
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    • pp.130-138
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    • 2002
  • Purpose : This study analyzed the prognostic factors affecting the survival rate and evaluated the role of radiation therapy in muscle-invading bladder cancer. Materials and Methods : Twenty eight patients with bladder cancer who completed planned definitive radiotherapy in the Departments of Therapeutic Radiology and Urology, Chonnam National University Hospital between Jan. 1986 to Dec. 1998 were retrospectively analyzed. The reviews were peformed based on the patients' medical records. There were 21 males and 7 females in this study. The median of age was 72 years old ranging from 49 to 84 years. All patients were confirmed as having transitional cell carcinoma with histological grade 1 in one patient, grade 2 in 15, grade 3 in 9, and uninformed in 3. Radiation therapy was peformed using a linear accelerator with 6 or 10 MV X-rays. Radiation was delivered daily with a 1.8 or 2.0 Gy fraction size by 4 ports (anterior-posterior, both lateral, alternatively) or 3 ports (Anterior and both lateral). The median radiation dose delivered to the isocenter of the target volume was 61.24 Gy ranging from 59 to 66.6 Gy. The survival rate was calculated by the Kaplan-Meier method. Multivariate analysis was peformed on the prognostic factors affecting the survival rate. Results : The survival rate was $76\%,\;46\%,\;33\%,\;33\%$ at 1, 2, 3, 5 years, respectively, with 19 months of median survival. The potential factors of age (less than 70 years vs above 70), sex, diabetes mellitus, hypertension, hydronephrosis, 1-stage (T3a vs T3b), TUR, chemotherapy, total duration of radiotherapy, radiation dose (less than 60 Gy vs above 60 Gy), and the treatment response were investigated with uniand multivariate analysis. Un univariate analysis, the T-stage (p=0.078) and radiation dose (p=0.051) were marginally significant, and the treatment response (p=0.011) was a statistically significant factor on the survival rate. Multivariate analysis showed there were no significant prognostic factors affecting the survival rate. Conclusion : The treatment response and radiation dose are suggested as th은 statistically significant factors affecting the survival rate of muscle invasive bladder cancer. A Further prospective randomized study is needed to confirm these prognostic factors.

An Analysis on the Reemployment of the Unemployed : Centered on the Applications of Human Capital and Human Capability Perspective (실업자의 재취업에 관한 분석: 인적자본관점(Human Capital Perspective)과 인간능력관점(Human Capability Perspective)의 적용)

  • Kang, Chul-Hee;Lee, Hong-Jik;Hong, Hyun-Mi-Ra
    • Korean Journal of Social Welfare
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    • v.57 no.3
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    • pp.223-249
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    • 2005
  • This study examines the hazard rate of reemployment by conducting the Cox regression analysis. In addition, two gender groups are subjected to comparative analysis to identify the effect of the factors related to the human capital and human capability perspective on reemployment. For this purpose, 1,871 cases are selected from the 5th year data from Korea Labor and Income Panel Study. The results of study are as follows. First, the factors of human capital, such as education, appropriateness of skill level, and job tenure hold negative impact on the probability of reemployment, while factors of human capability, such as basic learning ability, health insurance, social insurance, residential area(living in the Seoul metropolitan area) hold positive on the probability of reemployment. It is interesting note that there are different sets of factors that affect the probability of reemployment in the two gender groups. This trend is even more apparent in the case of factors that pertain to human capability. The results of this study imply that the factors of human capability, which stress the socio-institutional characteristics, should be considered as comparably significant compared to the factors that pertain to human capital when it comes to the estimation of reemployment. Also, results of this comparative study teach us that various perspectives, such as dual labor market theory and gender-segmented labor market theory, should be factored in for reemployment discussion as well. In conclusion, this research delivers several significant messages since it introduces the concept of human capability perspective, subjected to few empirical analyses in the past, and also heralds the way for comparative analysis on the impact of the factors pertaining to human capability on reemployment.

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Analysis of Prognositic Factors and Long-tenn Survival According to the Pattern of Lymph Node Metastasis in Surgically Resected N2 Non-Small Cell Lung Cancer(NSCLC) (N2 병기의 비소세포성 폐암 수술 후 림프절 전이 양태에 따른 생존율 비교 및 예후 인자 분석)

  • Chung, Kyung-Young;Kim, Si-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.4
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    • pp.474-485
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    • 2000
  • Background : Current studies on multimodal strategy for N2 non-small cell lung cancer are being high interest, have drawn much attention. N2 lung cancer, however, is composed of is divided into several sub groups with that have different prognoses. The prognostic factors still remain controversial. Methods : Between January 1990 and June 1999, 180 patients with N2 lung cancer who underwent surgical resection were investigated, excluding 10 of these for surgical mortality. All patients underwent mediastinal lymph node dissection. 20 clinicopathologic factors were investigated by univariable and multivariable analyses to identify significant prognostic factors among resected N2 disease. Results : The overall 5-year survival rate was 20.6%. Multivariable analyses among overall patients revealed 3 significant prognostic factors : Age, Histologic type, Vascular invasion. Based on the result, 49 patients with both age more than 60 and pathologic Non-squamous cell showed a 5-year survival of 5.0%, whereas 37 patients with neither of the factors showed a 5-year survival of 56.6%(p<0.001). And 12 patients with both vascular invasion and pathologic Non-squamous cell showed a 5-year survival of 11.9%, whereas 67 patients with neither of the factors showed a 5-year survival of 33.6%(p=0.01). Conclusion : The prognosis of surgically resected N2 disease varies according to the 3 significant prognosis factors. Tumor size may be an additional influencing factor in the prognosis of N2 disease.

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Inhibitory Activities of Water Extracts of Black Ginseng on HCl/Ethanol-Induced Acute Gastritis through Anti-Oxidant Effect (흑삼 열수 추출물의 항산화 효과를 통한 염산/에탄올로 유발된 위염 억제 작용)

  • Kim, Min Yeong;Kwon, O Jun;Noh, Jeong Sook;Roh, Seong-Soo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.9
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    • pp.1249-1256
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    • 2016
  • Black ginseng (BG) obtained by a 9-fold steaming process of Panax ginseng has been reported to have anti-oxidative, anti-obesity, and anti-diabetes effects. The current study evaluated the protective effect of BG by steaming time in an HCl/ethanol-induced acute gastritis model. BG was divided into four samples according to steaming-drying processing (Gin1, Gin3, Gin6, and BG). High performance liquid chromatography analysis, free radical scavenging activity, and total phenol and flavonoid contents were examined in ginseng and four BG samples. Compared with ginseng, BG showed a stronger radical scavenging effect and higher contents of total phenol and flavonoids. To evaluate the anti-gastritic effect of BG, mice were distributed into five groups: normal mice (N), acute gastritic mice with distilled water (CON), acute gastritic mice with 100 mg/kg of ginseng (Gin0), acute gastritic mice with 100 mg/kg of BG (BG), and acute gastritic mice with 10 mg/kg of sucralfate (SC). After 1 hour of pre-treatment with water, extracts (Gin0 and BG), or drug (SC), experimental groups except for N were orally administered 0.5 mL of 150 mM HCl/60% ethanol (v/v) mixture. Blood was collected 1 hour later from the heart, and gastric tissue was harvested. Reactive oxygen species (ROS) levels were measured in serum, and related protein expression was examined by Western blot assay. In HCl/ethanol-induced acute gastritic mice, treatment with ginseng or BG improved mucosal damage in the histological evaluation. The serum ROS level significantly decreased in the BG-treated group compared with the CON group. Furthermore, expression of inflammatory cytokines significantly decreased in the BG-treated group compared with the CON group. Based on these results, antioxidant and anti-gastritic activities of ginseng were enhanced by streaming-drying processing, in part due to an increase in biological active compounds.

RALY RNA Binding Protein-like Reduced Expression is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

  • Cui, Zhi-Wen;Xia, Ye;Ye, Yi-Wang;Jiang, Zhi-Mao;Wang, Ya-Dong;Wu, Jian-Ting;Sun, Liang;Zhao, Jun;Fa, Ping-Ping;Sun, Xiao-Juan;Gui, Yao-Ting;Cai, Zhi-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3403-3408
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    • 2012
  • The molecular mechanisms involved in the progression of clear cell renal cell carcinomas (ccRCCs) are still unclear. The aim of this study was to analyse the relationships between expression of RALYL and clinical characteristics. In 41 paired samples of ccRCCs and adjacent normal tissues, we used real-time qPCR to evaluate the expression of RALYL mRNA. RALYL protein levels were determined in 146 samples of ccRCC and 37 adjacent normal tissues by immunohistochemistry. Statistical analysis was used to explore the relationships between expression of RALYL and the clinical characteristics (gender, age, tumor size, T stage, N stage, M stage, survival times and survival outcome) in ccRCC. In addition, these patients were follow-up period 64 months (range: 4~116months) to investigate the influence on prognosis. We found significantly differences between ccRCC tissues and normal tissues (p<0.001, paired-sample t test) in mRNA levels of RALYL. Immunohistochemistry analyses in 146 ccRCC samples and 37 adjacent normal tissues showed significantly lower RALYL protein levels in ccRCC samples (${\chi}^2$-test, p<0.001), inversely correlating with tumour size (p=0.024), T stage (0.005), N stage (p<0.001) as well as M stage (p=0.019), but not age (p=0.357) and gender (p=0.348). Kaplan-Meier survival analysis demonstrated that people with lower level of RALYL expression had a poorer survival rate than those with a higher level of RALYL expression, significantly different by the log-rank test (p=0.011). Cox regression analysis indicated that RALYL expression (p=0.039), N stage (p=0.008) and distant metastasis (p<0.001) were independent prognosis factors for the overall survival of ccRCC patients. We demonstrated that the expression of RALYL was significantly low in ccRCC and correlated with a poor prognosis in a large number of clinical samples. Our findings showed that RALYL may be a potential therapeutic target as well as a poor prognostic factor.

Clinical Implications of p57KIP2 Expression in Breast Cancer

  • Xu, Xiao-Yin;Wang, Wen-Qian;Zhang, Lei;Li, Yi-Ming;Tang, Miao;Jiang, Nan;Cai, Shou-Liang;Wei, Liang;Jin, Feng;Chen, Bo
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.5033-5036
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    • 2012
  • Objective: To study the relationship between expression of $p57^{KIP2}$ and prognosis and other clinicopathological parameters in invasive breast cancers. Methods: We assessed the expression of $p57^{KIP2}$ in 89 cases of invasive breast cancer and 20 cases of normal breast tissue by immunohistochemical methods and analyzed the results with SPSS software (ver. 16.0). Result: The positive expression rates of $p57^{KIP2}$ protein in the invasive breast cancers and surrounding normal tissue were 30.3% (27/89) and 65% (13/20), respectively. Cases with no $p57^{KIP2}$ expression exhibited a significantly higher post-operative distant metastasis rate than those with $p57^{KIP2}$ expression (37.9% vs. 14.8%; P = 0.01). DFS analysis showed that $p57^{KIP2}$-/C-erbB-2+ tumors also exhibited a significantly higher post-operative distant metastasis rate than the other groups (66.7% vs. 29.2%; P = 0.007), as did $p57^{KIP2}$-/p53+ tumors (64.3% vs. 22.7%; P = 0.001). Survival analysis revealed that $p57^{KIP2}$ was associated with breast cancer-specific survival overall (P = 0.045, log-rank test). Subgroup analysis demonstrated that individuals with $p57^{KIP2}$-/C-erbB-2+tumors experienced significantly worse post-operative survival than those with $p57^{KIP2}$-/C-erbB-2- or other tumors (P = 0.006, log-rank test). $p57^{KIP2}$-/p53+ tumors were associated with significantly worse post-operative survival than $p57^{KIP2}$-/p53- or other tumors (P = 0.001, log-rank test). Cox regression analysis showed that $p57^{KIP2}$ was a non-independent prognostic factor for breast cancer (P = 0.303). Conclusions: $p57^{KIP2}$ is expressed at low levels in invasive breast cancer and is associated with better overall survival rate and disease-free survival in breast cancer patients, but it was a non-independent prognostic factor for breast cancer. Thus, the connection between $p57^{KIP2}$/p53 and $p57^{KIP2}$/C-erbB-2 may provide biomarkers for breast cancer.