• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3037-3046
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• 2012

The diffuse large B-cell lymphoma (DLBCL) encompasses two major groups of tumors with uneven survival outcomes - germinal center B-cell (GCB) and non-germinal center B-cell (non-GCB). In the present study, we investigated the expression of GCB markers (BCL-6 and CD10) and non-GCB markers (CD138 and MUM-1) in an effort to evaluate their prognostic value. Paraffin-embedded tumor biopsies of 46 Jordanian DLBCL patients were analyzed, retrospectively, by immunohistochemistry to investigate the expression of BCL-6, CD10, CD138 and MUM-1. In addition, survival curves were calculated with reference to marker expression, age, sex and nodal involvement. Positive expression of BCL-6, CD10, CD138 and MUM-1 was shown in 78%, 61%, 39% and 91% of the cases, respectively, that of BCL-6 being associated with better overall survival (p = 0.02), whereas positive CD138 was linked with poor overall survival (p = 0.01). The expression of CD10 and MUM-1 had no impact on the overall survival. Among the clinical characteristics studied, diagnosis at an early age, nodal involvement and maleness were associated with a higher overall survival for DLBCL patients. Our results underline the importance of BCL-6 as a marker of better prognosis and CD138 as a marker of poor prognosis for DLBCL patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8429-8433
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• 2014

Circulating tumor cells (CTCs) are believed to be particularly important and a reliable marker of malignancy. However, the prognostic significance of CTCs detected in patients with small cell lung cancer (SCLC) is still unclear. We therefore aimed to assess the prognostic relevance of CTCs using a meta-analysis. We searched PubMed for relevant studies and statistical analyses were conducted to calculate the hazard ratio (HR) and 95% confidence intervals (CIs) using fixed or random-effect models according to the heterogeneity of included studies. A total of 7 papers covering 440 SCLC patients were combined in the final analysis. The meta-analysis revealed that CTCs were significantly associated with shorter overall survival (HR=1.9; 95%CI: 1.19-3.04; Z=2.67; P<0.0001) and progression-free survival (HR=2.6; 95%CI: 1.9-3.54; Z=6.04; P<0.0001). The results thus suggest that the presence of CTCs indicates a poor prognosis in patients with SCLC. Further well-designed prospective studies are required to explore the clinical applications of CTCs in SCLC.

• Toxicological Research
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• 제11권1호
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• pp.127-131
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• 1995

Sequential changes in cell proliferation during the development of epitherial kidney tumors induced in rats were investigated by autoradiographic determination of the $^3H$-thymidine-labeling index. Renal cell tumors were induced in male Sprague-Dawley rats by oral administration of N-nitrosomorpholine at the concentration of 120 mg/l in the drinking water for 7 weeks. At different times between 12 and 34 weeks after withdrawal of the carcinogen (stop model) animals were sacrificed. According to cytological criteria, neoplastic lesions were classified into clear cell, acidophilic cell, basophilic cell and oncocytic tumors. The labeling index was found to be increased in all types of preneoplastic tubules as compared to their corresponding original tubules. A much stronger elevation of cell proliferation was ocurred during the development of renal cell tumors from preneoplastic tubules. Of four tumor types, acidophilic cell tumor showed the highest labeling index while oncocytoma exhibited the lowest proliferative activity. These findings are in good accordance with the clinical observations that acidophilic cell tumors have a worse prognosis than oncocytoma. The data presented in this study suggest that the individual proliferation rates may be an objective biological marker of kidney tumor aggressiveness.

• Journal of Korean Neurosurgical Society
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• 제57권2호
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• pp.73-76
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• 2015

Objective : Tumor necrosis factor alpha (TNF-${\alpha}$) have proven effects in pathogenesis of neuroinflammation after spinal cord injury (SCI). Current study is designed to evaluate the effects of an anti-TNF-${\alpha}$ agent, adalimumab, on spinal cord clip compression injury in rats. Methods : Thirty two male adult Wistar rats were divided into four groups (sham, trauma, infliximab, and adalimumab groups) and SCI was introduced using an aneurysm clip. Animals in treatment groups received 5 mg/kg subcutaneous adalimumab and infliximab right after the trauma. Malondialdehyde (MDA) levels were studied in traumatized spinal cord tissues 72 hours after the injury as a marker of lipid peroxidation. Results : Animals that received anti-TNF-${\alpha}$ agents are found to have significantly decreased MDA levels. MDA levels were significantly different between the trauma and infliximab groups (p<0.01) and trauma and adalimumab groups (p=0.022). There was no significant difference in neurological evaluation of the rats using Tarlov scale. Conclusion : These results suggest that, like infliximab, adalimumab has favorable effects on lipid peroxidation induced by spinal cord trauma in rats.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.381-384
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• 2014

Background: Evidence indicates that Dickkopf-1 (DKK-1) levels may be a biomarker for cancer risk. The aim of this study was to assess DKK-1 and its correlation with clinic-pathological features in patients with bladder cancer. Materials and Methods: DKK-1 levels were determined in serum samples from 90 patients with bladder cancer before transurethral tumor resection. The concentrations of DKK-1 were determined by using enzyme linked immune-sorbent assay (ELISA). Results: Elevated preoperative DKK-1 levels were associated with tumor stage (p<0.001), grade (p<0.001) and histological grade (p<0.001). Conclusions: The results of our study demonstrated that the level of serum DKK-1 is correlated with both disease progression and increase in the tumor grade. Preoperative serum DKK-1 elevation may thus represent a novel marker for the determination of bladder cancer and the detection of patients with a likely poor clinical outcome.

• 한국식품영양과학회지
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• 제25권5호
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• pp.865-870
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• 1996

감잎의 시료 중 항돌연변이 효과와 암세포 증식 억제효과가 컸던 감잎의 헥산, 클로로포름 획분 및 감잎 탄닌의 항암효과를 Sarcoma-180 종양세포를 이용하여 살펴 보았다. Sarcoma-180 종양세포에 대한 시료의 세포 독성작용을 관찰한 후 세포에 큰 영향을 주지 않는 범위내에서 고형암 성장저지 효과 및 수명 연장 효과를 살펴 본 결과 감잎의 헥산 획분이 59.6%로 가장 높은 고형암 성장 저지율을 나타냈으며 수명 연장 효과도 대조군의 경우 17.4일인데 반해 헥산 획분을 투여한 경우 생존일수가 23.6일로 가장 큰 수명 연장 효과가 관찰되었다. 면역 관련 장기 중 하나인 비장의 체중에 대한 중량 변화는 대조군의 경우 0.6%인데 반해 감잎의 헥산 및 클로로포름 획분 그리고 감잎 탄닌의 경우 0.7%, 0.8%, 0.8%로 약간의 증가를 나타내었다.

• Molecules and Cells
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• 제40권7호
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• pp.515-522
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• 2017

CD133, a pentaspan transmembrane glycoprotein, is generally used as a cancer stem cell marker in various human malignancies, but its biological function in cancer cells, especially in glioma cells, is largely unknown. Here, we demonstrated that forced expression of CD133 increases the expression of IL-$1{\beta}$ and its downstream chemokines, namely, CCL3, CXCL3 and CXCL5, in U87MG glioma cells. Although there were no apparent changes in cell growth and sphere formation in vitro and tumor growth in vivo, in vitro trans-well studies and in vivo tumor xenograft assays showed that neutrophil recruitment was markedly increased by the ectopic expression of CD133. In addition, the clinical relevance between CD133 expression and IL-$1{\beta}$ gene signature was established in patients with malignant gliomas. Thus, these results imply that glioma cells expressing CD133 are capable of modulating tumor microenvironment through the IL-$1{\beta}$ signaling pathway.

• Molecules and Cells
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• 제41권5호
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• pp.381-389
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• 2018

ARF is a tumor suppressor protein that has a pivotal role in the prevention of cancer development through regulating cell proliferation, senescence, and apoptosis. As a factor that induces senescence, the role of ARF as a tumor suppressor is closely linked to the p53-MDM2 axis, which is a key process that restrains tumor formation. Thus, many cancer cells either lack a functional ARF or p53, which enables them to evade cell oncogenic stress-mediated cycle arrest, senescence, or apoptosis. In particular, the ARF gene is a frequent target of genetic and epigenetic alterations including promoter hyper-methylation or gene deletion. However, as many cancer cells still express ARF, pathways that negatively modulate transcriptional or post-translational regulation of ARF could be potentially important means for cancer cells to induce cellular proliferation. These recent findings of regulators affecting ARF protein stability along with its low levels in numerous human cancers indicate the significance of an ARF post-translational mechanism in cancers. Novel findings of regulators stimulating or suppressing ARF function would provide new therapeutic targets to manage cancer- and senescence-related diseases. In this review, we present the current knowledge on the regulation and alterations of ARF expression in human cancers, and indicate the importance of regulators of ARF as a prognostic marker and in potential therapeutic strategies.

• 대한방사선치료학회지
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• 제22권1호
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• pp.25-32
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• 2010

목 적: 종양의 움직임을 고려하여 치료할 수 있는 RPM (Real time Position Management, Varian, USA) system을 사용하여 호흡을 고려한 방사선치료 시행 시, 제조사에서 제공하는 적외선 반사체는 일정각도 이상 couch가 회전할 경우 호흡신호 획득이 불가능하다. 이런 단점을 개선하고자 본 저자는 어느 각도에서나 호흡신호를 얻을 수 있는 3차원 적외선 반사체(3D infrared reflective marker)를 자체 개발하여 Kw-반사체라 명하고 그 유용성을 평가 하고자 한다. 대상 및 방법: 호흡신호의 안정성을 측정하기 위해 호흡운동을 재현 할 수 있는 3차원 구동팬텀(3D moving phantom) 위에 3가지 조건(A: couch 0도, 제조사의 반사체 B: couch 0도, Kw-반사체 C: couch 90도, Kw-반사체)의 적외선 반사체를 올려놓고 각각 3분 동안 호흡신호를 획득 하였다. 획득한 호흡신호는 호흡분석 프로그램(Labview ver 7.0)을 통해 최고값(peak value), 최저값(valley value), 표준편차(standard deviation), 변동값(variation value), 진폭값(amplitude value)을 획득하였다. 타겟의 회전 오차와 타겟의 이동범위를 알아보기 위해 3차원 구동팬텀 위에 B.B팬텀을 올려놓고 온-보드 영상장치(OBI)로 couch 0도와 90도 이미지를 획득한 후 B.B팬텀 중심에 위치한 ball bearing의 X, Y, Z값(mm)을 획득하였다. 결 과: 호흡신호를 분석한 결과 최고점에서 표준편차가 A: 0.002 B: 0.002 C: 0.003이고 진폭에 대한 호흡의 안정성은 A: 0.15% B: 0.14% C: 0.13%로 Kw반사체는 안정적으로 호흡신호를 얻을 수 있었다. couch 90도 회전 시 타겟인 ball bearing의 평균 회전오차는 X: -1.25 mm Y: -0.45 mm Z: +0.1 mm로 모든 방향에서 평균 1.3 mm 이내이고 타겟의 이동범위 차이도 평균 0.3 mm 이내였다. 결 론: couch가 회전하는 비동일면(Non-coplanar) 치료 시 Kw-반사체로 호흡신호를 얻은 결과 Kw-반사체는 안정적인 호흡신호를 획득할 수 있었고 제조사의 적외선반사체를 대체하기에 충분했다. 타겟의 회전오차와 이동범위 차이가 거의 없어 couch 회전 시 반사체 움직임의 변위가 호흡신호의 scale 및 진폭을 변화시킨 원인임을 알 수 있었다. 향후 couch angle값에 따른 진폭 높이의 변환 값을 연구해 적용한다면 비동일면에 대한 위상기반 gating 치료도 가능 할 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4603-4608
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• 2015

Background: To determine the potential value of serum tumor markers in predicting pCR (pathological complete response) during neoadjuvant chemotherapy. Materials and Methods: We retrospectively monitored the pro-, mid-, and post-neoadjuvant treatment serum tumor marker concentrations in patients with locally advanced breast cancer (stage II-III) who accepted pre-surgical chemotherapy or chemotherapy in combination with targeted therapy at Fudan University Shanghai Cancer Center between September 2011 and January 2014 and investigated the association of serum tumor marker levels with therapeutic effect. Core needle biopsy samples were assessed using immunohistochemistry (IHC) prior to neoadjuvant treatment to determine hormone receptor, human epidermal growth factor receptor 2(HER2), and proliferation index Ki67 values. In our study, therapeutic response was evaluated by pCR, defined as the disappearance of all invasive cancer cells from excised tissue (including primary lesion and axillary lymph nodes) after completion of chemotherapy. Analysis of variance of repeated measures and receiver operating characteristic (ROC) curves were employed for statistical analysis of the data. Results: A total of 348 patients were recruited in our study after excluding patients with incomplete clinical information. Of these, 106 patients were observed to have acquired pCR status after treatment completion, accounting for approximately 30.5% of study individuals. In addition, 147patients were determined to be Her-2 positive, among whom the pCR rate was 45.6% (69 patients). General linear model analysis (repeated measures analysis of variance) showed that the concentration of cancer antigen (CA) 15-3 increased after neoadjuvant chemotherapy in both pCR and non-pCR groups, and that there were significant differences between the two groups (P=0.008). The areas under the ROC curves (AUCs) of pre-, mid-, and post-treatment CA15-3 concentrations demonstrated low-level predictive value (AUC=0.594, 0.644, 0.621, respectively). No significant differences in carcinoembryonic antigen (CEA) or CA12-5 serum levels were observed between the pCR and non-pCR groups (P=0.196 and 0.693, respectively). No efficient AUC of CEA or CA12-5 concentrations were observed to predict patient response toward neoadjuvant treatment (both less than 0.7), nor were differences between the two groups observed at different time points. We then analyzed the Her-2 positive subset of our cohort. Significant differences in CEA concentrations were identified between the pCR and non-pCR groups (P=0.039), but not in CA15-3 or CA12-5 levels (p=0.092 and 0.89, respectively). None of the ROC curves showed underlying prognostic value, as the AUCs of these three markers were less than 0.7. The ROC-AUCs for the CA12-5 concentrations of inter-and post-neoadjuvant chemotherapy in the estrogen receptor negative HER2 positive subgroup were 0.735 and 0.767, respectively. However, the specificity and sensitivity values were at odds with each other which meant that improving either the sensitivity or specificity would impair the efficiency of the other. Conclusions: Serum tumor markers CA15-3, CA12-5, and CEA might have little clinical significance in predicting neoadjuvant treatment response in locally advanced breast cancer.