• Journal of Korean Neurosurgical Society
• /
• 제55권1호
• /
• pp.5-11
• /
• 2014

Objective : We evaluated pseudoprogression (PsPD) following radiation therapy combined with concurrent temozolomide (TMZ), and we assessed pseudoresponse following anti-angiogenic therapy for patients with recurrent disease using the Response Assessment of the Neuro-Oncology Working Group. Methods : Patients who were pathologically confirmed as having high-grade glioma received radiotherapy with concurrent TMZ followed by adjuvant TMZ. Bevacizumab (Avastin) with CPT-11 were used as a salvage option for cases of radiologic progression. Magnetic resonance imaging (MRI) was routinely performed 1 month after concurrent radiochemotherapy (CRT) and every 3 months thereafter. For cases treated with the bevacizumab-containing regimen for progressive disease, MRI was performed every 2 months. Results : Of 55 patients, 21 (38%) showed radiologic progression within 4 weeks after CRT. Of these patients, 16 (29%) showed progression at second post-CRT MRI (etPD) and five (9%) showed improvement (PsPD). Seven of thirty-four initially non-progressed patients showed progression at the second post-CRT MRI (ltPD). No difference in survival was observed between the etPD and ltPD groups (p=0.595). Five (50%) of ten patients showed a radiological response after salvage bevacizumab therapy. Four of those patients exhibited rapid progression immediately after discontinuation of the drug (drug holiday). Conclusion : Twelve weeks following treatment could be the optimal timing to determine PsPD or true progression. MRI with gadolinium enhancement alone is not sufficient to characterize tumor response or growth. Clinical correlation with adequate follow-up duration and histopathologic validation may be helpful in discriminating PsPD from true progression.

• 대한핵의학회지
• /
• 제30권3호
• /
• pp.344-350
• /
• 1996

Iododeoxyuridine의 유사체인 Iodine-131-5-Iodo-2'-O-methyluridine을 합성하여 종양세포의 증식을 영상화하고자 하였다. 2'-O-methyluridine을 이용하여 Iodine-131-Iodomethyluridine을 요오드발생 반응(Iodogen reaction)으로 간편하게 합성하였고 이를 이용한 자가방사영상과 핵의학영상에서 종양세포의 증식을 영상화 할 수 있었다. 이상의 결과는 Iodine-131-Iodomethyluridine을 이용하여 종양세포의 증식을 감마카메라로 영상화하여 세포증식이 활발한 생존 종양조직이나 재발을 평가할 수 있는 가능성이 있음을 시사한다.

• Molecules and Cells
• /
• 제39권8호
• /
• pp.631-638
• /
• 2016

Glutathione peroxidase 3 (GPx3), an antioxidant enzyme, acts as a modulator of redox signaling, has immunomodulatory function, and catalyzes the detoxification of reactive oxygen species (ROS). GPx3 has been identified as a tumor suppressor in many cancers. Although hyper-methylation of the GPx3 promoter has been shown to down-regulate its expression, other mechanisms by which GPx3 expression is regulated have not been reported. The aim of this study was to further elucidate the mechanisms of GPx3 regulation. GPx3 gene analysis predicted the presence of ten glucocorticoid response elements (GREs) on the GPx3 gene. This result prompted us to investigate whether GPx3 expression is regulated by the glucocorticoid receptor (GR), which is implicated in tumor response to chemotherapy. The corticosteroid dexamethasone (Dex) was used to examine the possible relationship between GR and GPx3 expression. Dex significantly induced GPx3 expression in H1299, H1650, and H1975 cell lines, which exhibit low levels of GPx3 expression under normal conditions. The results of EMSA and ChIP-PCR suggest that GR binds directly to GRE 6 and 7, both of which are located near the GPx3 promoter. Assessment of GPx3 transcription efficiency using a luciferase reporter system showed that blocking formation of the GR-GRE complexes reduced luciferase activity by 7-8-fold. Suppression of GR expression by siRNA transfection also induced down-regulation of GPx3. These data indicate that GPx3 expression can be regulated independently via epigenetic or GR-mediated mechanisms in lung cancer cells, and suggest that GPx3 could potentiate glucocorticoid (GC)-mediated anti-infla-mmatory signaling in lung cancer cells.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권6호
• /
• pp.2989-2993
• /
• 2016

The commonest cancer in Egyptian females occurs in the breast cfDNA is a non-invasive marker for tumor detetion and prognostic assessment in many types of cancer including breast cancer. This study aimed to assess the role of cfDNA and its fragmentation pattern in breast cancer prognosis and treatment response. Forty female patients with malignant breast tumors and a comparable group of healthy blood donors were enrolled prospectively. cfDNA levels and fragmentation patterns were investigated after cfDNA extraction, gel electrophoresis and gel analysis. The percentage of breast cancer patients positive for cfDNA (92.5%) was significantly higher than that of controls (55%). Also, mean concentration of cfDNA was significantly higher than in the control group (P<0.05). Most Her-2 positive patients had long cfDNA fragments, this being significant as compared to Her-2 negative patients (P<0.05). Metastasis was also positively linked to significantly higher cfDNA (P<0.05) and the mean cfDNA integrity index was significantly higher in non-responders compared to treatment responders (P<0.05). In conclusion, both qualitative and quantitative aspects of cfDNA and its different fragments in breast cancer patients could be related to prognosis, metastasis and treatment response. Long cfDNA fragments could be particularly useful for prediction purposes.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권11호
• /
• pp.4659-4664
• /
• 2015

Background: ABC proteins are one key type of transport superfamilies which undertake majority of drug transport, which affect the osteosarcoma response to chemotherapeutics. Previous studies have suggested the association between ABC polymorphisms and osteosarcoma response. However, the results of previous studies remain controversial. Therefore, we perform a meta-analysis to get a more precise estimation of this association. The association between ABC polymorphisms and osteosarcoma response was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Three polymorphisms of ABC including ABCB1 rs1128503, ABCC3 rs4148416 and ABCC2 rs717620 polymorphism were investigated. Overall, significant association was observed between ABCC3 rs4148416 polymorphism and osteosarcoma response under allele contrast (T vs. C: OR=1.73, 95%CI=1.09-2.74, P=0.019), homozygote comparison (TT vs. CC: OR=2.00, 95%CI=1.25-3.23, P=0.004), recessive genetic model (TT vs. TC/CC: OR=1.80, 95%CI=1.14-2.84, P=0.011) and dominant genetic model (TT/TC vs. CC: OR=1.70, 95%CI=1.20-2.42, P=0.003). Moreover, significant association was also observed in Caucasian population rather than Asian population for ABCB1 rs1128503 polymorphism. We conclude that ABCC3 rs4148416 polymorphism was significantly associated with poor osteosarcoma response and ABCB1 rs1128503 polymorphism was significantly associated with good osteosarcoma response in Caucasian population rather than Asian population.

• 대한영상의학회지
• /
• 제84권6호
• /
• pp.1244-1256
• /
• 2023

전립선암에서 뼈는 가장 흔한 전이병소이며, 전립선암의 질병 상태를 파악하고 치료 반응을 평가하기 위해서는 전이성 골병변의 평가가 필수적이다. 거세 저항성 전립선암은 남성호르몬을 거세 수치로 떨어뜨렸음에도 불구하고 암이 진행하는 상태를 의미하며, 이 상태에서는 원격 전이가 빈번하게 발생한다. 거세 저항성 전립선암의 치료 반응을 객관적으로 평가하기 위해 뼈스캔을 기반으로 한 Prostate Cancer Working Group 3 (이하 PCWG3) 가이드라인이 발표되었으나 실제 이를 쉽게 숙지하여 적용하기에는 어려운 점이 있다. 본 종설에서 PCWG3 가이드라인에 준한 거세 저항성 전립선암의 뼈스캔 기반 골병변 반응 평가를 위한 구체적인 영상 획득 방법 및 치료 반응 평가법을 소개하고자 한다.

• IMMUNE NETWORK
• /
• 제3권1호
• /
• pp.38-46
• /
• 2003

Background: Platelet-activating factor (PAF) induces nuclear factor $(NF)-{\kappa}B$ activation and angiogenesis and increases tumor growth and pulmonary tumor metastasis in vivo. The role of $NF-{\kappa}B$ activation in PAF-induced angiogenesis in a mouse model of Matrigel implantation, and in PAF-mediated pulmonary tumor metastasis were investigated. Methods: Angiogenesis using Matrigel and experimental pulmonary tumor metastasis were tested in a mouse model. Electrophoretic mobility shift assay was done for the assessment of $NF-{\kappa}B$ translocation to the nucleus. Expression of angiogenic factors, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\alpha}$, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were tested by RT-PCR and ELISA. Results: PAF induced a dose- and time-dependent angiogenic response. PAF-induced angiogenesis was significantly blocked by PAF antagonist, CV6209, and inhibitors of $NF-{\kappa}B$ expression or action, including antisense oligonucleotides to p65 subunit of $NF-{\kappa}B$ (p65 AS) and antioxidants such as ${\alpha}$-tocopherol and N-acetyl-L-cysteine. In vitro, PAF activated the transcription factor, $NF-{\kappa}B$ and induced mRNA expression of $TNF-{\alpha}$, $IL-1{\alpha}$, bFGF, VEGF, and its receptor, KDR. The PAF-induced expression of the above mentioned factors was inhibited by p65 AS or antioxidants. Also, protein synthesis of VEGF was increased by PAF and inhibited by p65 AS or antioxidants. The angiogenic effect of PAF was blocked when anti-VEGF antibodies was treated or antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF was co-administrated, but not by antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF each alone. PAF-augmented pulmonary tumor metastasis was inhibited by p65 AS or antioxidants. Conclusion: These data indicate that PAF increases angiogenesis and pulmonary tumor metastasis through $NF-{\kappa}B$ activation and expression of $NF-{\kappa}B$-dependent angiogenic factors.

• 대한핵의학회지
• /
• 제26권1호
• /
• pp.14-25
• /
• 1992

Thallium-201 $(^{201}T1)$ SPECT studies were performed on a normal volunteer and 12 patients with intracerebral lesions: 3 patients with gliomas, 3 patients with meningiomas, 1 patient each with metastatic tumor, brain abscess, and cerebral infarction, and 3 postirradiation patients. (2 with metastatic tumors, 1 with lymphoma). A $^{201}T1$ index, based on the ratio of $^{201}T1$ uptake in the brain lesion versus the homologous contralateral brain, was calculated and compared with tumor histology and CT/MRI findings. The SPECT $^{201}T1$ scan showed minimal uptake of tracer in a normal brain. There was substantial uptake of $^{201}T1$ in high-grade gliomas (index>1.5) with little uptake in low-grade lesions. A previously irradiated patient with recurrent astrocytoma, in whom MRI study was unable to distinguish tumor recurrence from necrosis, showed the lesions with high $^{201}T1$ indices in both hemispheric regions (2.50/1.93), suggesting tumor recurrence. Two meningiomas and a metastatic tumor showed varying degrees of $^{201}T1$ uptake (index $1.71\sim8.15$), revealing that $^{201}T1$ uptake is not exclusive to high-grade gliomas. In 2 postirradiation patients with metastatic tumors, no abnormal $^{201}T1$ uptake was found in the cerebral lesions, shortly after the initiation of radiation therapy or despite the persistence of enhancing lesions-though improved-on MR images, suggesting that $^{201}T1$ uptake may reflect the metabolic and possibly clonogenic activities of tumors and the brain $^{201}T1$ SPECT imaging might be valuable for the evaluation of tumor responsiveness to the therapy and for early detection of tumor recurrence. A patient with brain abscess on antibiotic treatment, showig increased uptake of $^{201}T1$ in the resolving lesions (index 2.87/1.52) is discussed. In a patient with cerebral infarction, there was no abnormal uptake of $^{201}T1$ in infarcted tissue. When using a threshold index of 1.5, correlation rate between $^{201}T1$ uptake and contrast enhancement of the cerebral lesions on CT/MRI was 73% (8/11). In conclusion, the brain $^{201}T1$ SPECT imaging may be useful for assessment of tumor response to the therapy and to predict low-or high-grade lesions.

• 한국식품영양과학회:학술대회논문집
• /
• 한국식품영양과학회 2004년도 Annual Meeting and International Symposium
• /
• pp.271-274
• /
• 2004

Nutritional genomics is a new field of study of how nutrition interacts with an individual's genome or individual responds to individual diets. Systematic approach of nutritional genomics will likely provide important clues about responders and non-responders. The current interest in personalizing health stems from the breakthroughs emerging in integrative technologies of genomics and epigenomics and the identification of genetic and epigentic diversity in individual's genetic make-up that are associated with variations in many aspects of health, including diet-related diseases. Microarray is a powerful screen system that is being also currently employed in nutritional research. Monitoring of gene expression at genome level is now possible with this technology, which allows the simultaneous assessment of the transcription of tens of thousands of genes and of their relative expression of pathological cells such tumor cells compared with that of normal cells. Epigenetic events such as DNA methylation can result in change of gene expression without involving changes in gene sequence. Recent developed technology of DNAarray-based methylation assay will facilitate wide study of epigenetic process in nutrigenomics. Some of the areas that would benefitfrom these technologies include identifying molecular targets (Biomarkers) for the risk and benefit assessment. These characterized biomarkers can reflect expose, response, and susceptibility to foods and their components. Furthermore the identified new biomarker perhaps can be utilized as a indicator of delivery system fur optimizing health.

• Radiation Oncology Journal
• /
• 제3권1호
• /
• pp.41-50
• /
• 1985

한국에서는 식도암의 임상적 관찰과 치료성적이 아직까지는 광범위하게 연구 및 보고되지 않았지만, 소화기계통에서 발생하는 악성종양 중에서는 비교적 적지 않은 것으로 알려져 있다. 의학적 지식, 진단적 설비, 방사선 치료의 적용, 외과적 수술의 진보, 그리고 최근의 화학요법의 재발 등과 같은 괄목할만한 향상에도 불구하고 예후는 극히 불량하여 5년 생존율이 10%이하로서, 과거에 비하여 크게 향상되지 않은 것으로 보고되고 있다. 이에 저자들은 1970년 1월부터 1980년 12월까지 만 11년 동안 식도암으로 진단되어 연세 암 센터에서 근치적 목적으로 방사선 치료를 받았던 63예에 대한 철저한 추적조사를 통하여 후향성 분석을 시행한 바 다음과 같은 결과를 얻었다. 1. 전 63예의 식도암 환자의 85.2%인 52예는 조직병리학적 소견에서 상피성세포암(Epidermoid Carcinoma)으로 확진되었다. 그리고 $T_1$인 17예를 제외한 46예73%의 병변은 상당히 진행되였던 예들이였다. 2. 방사선 조사선량은 일일 일회 2Gys가 조사되였으며 총 조사선량 $50{\sim}74Gys$가 $5{\sim}8$주간에 조사되었다. 3. 전 63예중 28예에서 방사선 치료 후 1개월만에 식도조형상을 통하여 식도암에 대한 방사선치료 효과를 평가하여 본 결과, 완전관해는 7예였으며 나머지 15예는 부분적 관해, 그리고 6예는 변화가 없었다. 4. 전 63예의 3년, 5년 생존율은 11.8%, 8.8%였으며 그리고 $T_1$인 17예의 3년, 5년 생존율은 24.7%, 20.8%였다.