• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3611-3615
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• 2012

Objective: The objective of this study was to establish the diagnostic accuracy, specificity and sensitivity of fine needle aspiration cytology(FNAC) for intra-oral tumors, comparing with histopathology as the gold standard. Materials and methods: Forty cases of FNA cytology from intraoral tumors was performed in AFID along with the demographic data and clinical information and then diagnosed at AFIP, Rawalpindi. Then the cytology results obtained per FNAC were compared with the histopathological biopsy results of the same lesions. The following variables were recorded for each patient: Age, gender, site of biopsy, diagnosis. The data were entered and analyzed using Open-epi version 2.0. Diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value were calculated. Cohen Kappa was further applied to compare the agreement between the biopsy and FNAC diagnoses. A p-value of < 0.05 was considered as statistically significant. Results: Among the total patients included in the study there were 24 males and 16 females, with a ratio of 1.5:1. Age of the patients ranged from 24 to 80 years with a mean of 52 years. A total of six sites were aspirated from the oral cavity with maximum (11) aspirates taken from alveolar ridge. The results of FNAC revealed that there were 32 malignant and 8 benign aspirates. Confirmation through histopathological analysis came for 31/32 malignant cases while one was falsely given positive for malignancy on FNAC. Among a total of 40 cases, 31(77%) cases diagnosed were found to be malignant and remaining 9(23%) were benign. The FNAC results revealed 32 malignant and 8 benign lesions. Histopathology of the subsequent surgically excised specimen showed malignant lesions in 31(77%) and benign in 9(23%) patients. As a whole, it was found that the absolute sensitivity for introral FNAC was 100% and specificity 89% with positive predictive value of 97% and negative predictive value of 100%. Conclusion: Cytological diagnosis was almost corroborative with final histopathological diagnosis in all cases, with very few exceptions, exhibiting high diagnostic accuracy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7071-7076
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• 2015

Epidermal growth factor receptor (EGFR) is one of the targeted molecular markers in many cancers including lung malignancies. Gefitinib and erlotinib are two available therapeutics that act as specific inhibitors of tyrosine kinase (TK) domains. We performed a case-control study with formalin-fixed paraffin-embedded tissue blocks (FFPE) from tissue biopsies of 167 non-small cell lung carcinoma (NSCLC) patients and 167 healthy controls. The tissue biopsies were studied for mutations in exons 18-21 of the EGFR gene. This study was performed using PCR followed by DNA sequencing. We identified 63 mutations in 33 men and 30 women. Mutations were detected in exon 19 (delE746-A750, delE746-T751, delL747-E749, delL747-P753, delL747-T751) in 32 patients, exon 20 (S786I, T790M) in 16, and exon 21 (L858R) in 15. No mutations were observed in exon 18. The 63 patients with EFGR mutations were considered for upfront therapy with oral tyrosine kinase inhibitor (TKI) drugs and have responded well to therapy over the last 15 months. The control patients had no mutations in any of the exons studied. The advent of EGFR TKI therapy has provided a powerful new treatment modality for patients diagnosed with NSCLC. The study emphasizes the frequency of EGFR mutations in NSCLC patients and its role as an important predictive marker for response to oral TKI in the south Indian population.

• 생명과학회지
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• 제26권5호
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• pp.584-591
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• 2016

삼백초는 항산화 활성을 갖는 플라보노이드 화합물을 포함하고 있는 여러해살이 식물로 알려져 있다. 본 연구에서는 삼백초 물 추출물과 유기용매 분획물의 항산화 활성, 항염증 활성 및 PMA에 의해 유도된 MMP-2 및 MMP-9활성 억제 효과를 조사하였다. 시료들은 삼백초 물 추출을 헥산(hexane), 클로로포름(CHCl₃), 에틸 아세테이트(Ethyl acetate), 부탄올(butanol) 및 물(water)과 같은 용매로 분획화하여 사용하였고, 물 분획물의 수득율이 9.25%로 가장 높았다. 항산화 활성은 DPPH assay, 세포 생존율 측정은 MTS assay, 항염증 활성은 마우스 대식세포 Raw 264.7세포에서NO 생성 그리고 MMP-2 및 MMP-9의 mRNA 발현 및 단백질 활성 억제는 인간구강편평세포암종 YD-10B 세포에서 RT-PCR과 zymography방법을 통해 측정하였다. 본 연구의 결과에 의하면 MMP-2/-9 활성은 PMA에 의해 YD-10B세포에서 증가하였다. PMA 처리된 YD-10B 세포에서, 에틸 아세테이트 분획물이 증가된 MMP-2/-9의 mRNA 발현 및 단백질 활성을 유의하게 억제하였다. 그리고 항산화 활성도 에틸아세트 분획물이 73.38%의 가장 높게 나타났다. 또한 세포 독성을 나타내지 않는 농도에서, 에틸아세트 분획물이 Raw 264.7세포에서 농도 의존적으로 유의하게 항염증 활성을 보였다. 그러므로 본 연구에서는 삼백초 물 추출의 에틸아세트 분획물이 구강암의 암 침윤을 억제할 수 있는 효과적인 암 예방 및 치료를 위한 항암제로서의 가능성을 암시하고 있다.

• Biomolecules & Therapeutics
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• 제25권5호
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• pp.545-552
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• 2017

Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett's test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in $C_{max}$, and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in $C_{max}$ and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.

• Radiation Oncology Journal
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• 제15권4호
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• pp.321-329
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• 1997

목적 : 두경부 암 환자에서 경부 림프절 전이 가능성이 높아지는 것은 원발병소의 해부학적위치 및 특성, 원발병소의 크기 즉 병기와 조직병리학적 종류 따라 영향을 받는다. 두경부 암 환자에서 경부 림프절의 전이 양상은 다른 나라에서 분석, 연구되어 있고, 현재 두경부 암 환자 치료와 처치를 이를 기조로 하여 사용한다. 그러나, 두경부 암 환자에 대한 경부 림프절 전이에 대한 우리나라 환자의 통계는 없어 이번 통계를 시행하게 되었다. 대상 및 방법 : 1981년 11월부터 1995년 12월까지 본 병원 방사선 종양학과에 내원한 환자중초사가 가능한 997명을 대상으로 하였다. 조사는 방사선 종양학과에 내원시 면밀한 경부 촉진과향께 컴퓨터 단층 촬영영상 상에서 확인을 하였다. 환자는 크게 경부 림프절 전이가 있는 군과 전이가 없는 군으로 나누었고, 경부 림프절의 병기는 미국 암 연합회에서 추천한 방식에 의하였다. 원발병소의 위치 및 주위로의 침윤 등은 면밀한 관찰과 촉진, 컴퓨터 단층 촬영 영상, 수술소견 및 조직병리학 소견을 참조하였다. 결 과 :방사선 종양학과에 방사선 치료를 위해 내원한 997명 중 416명$(42\%)$에서 경부 림프절 전이를 뽀였고, 581명$(58\%)$에서 전이를 보이지 않았다. 경부 림프절 전이를 보인 림프절의 병기분포를 관찰한 결과 다음과 같았다. Hl : 106$(25.5\%)$, N2a 100$(24\%)$, N2b :68$(16.4\%)$, N2c : 69$(16.6\%)$, N3 :73$(15\%)$. 두경부 암 환자에서 원발병소의 빈도는 다음과 같다. 후두암 : 283$(28.5\%)$, 부비동암 : 152$(18\%)$, 구인두암: 144$(14.5\%)$, 비인강암: In$(12\%)$, 구강암 :92$(9\%)$, 하인두암:71$(7\%)$, 타액선암:$58(6\%)$, 미지원발부위암:31$(3\%)$, 피부암: $14(2\%)$. 두경부 암 환자 중 가장 경부 림프절 전이가 높은 원발병소는 비인강암$(71\%)$으로 나타났고, 다음은 하인두암$(69\%)$, 구인두암$(64\%)$, 구강암$(39\%)$ 순이었다. 경부 림프절 전이를 보였던, 416명 중에서는 구인두암 92명$(22\%)$, 비인강암 8f명$(21\%)$, 후두암 79명$(19\%)$의 순이였다. 병리조직학적으로 가장 빈도가 높을 것은 편평상피암증으로 전체 환자 중 $65.4\%$을 차지하였고, 다음은 악성 림프종이 109명으로 $11\%$였다. 결론 : 두경부 암 환자에서 경부 림프절 전이의 양상이 외국 통계와 비교 매우 유사하게 나타났으며, 원발병소의 해부학적 특성에 따라 경부 림프절 전이가 좌우되며 원발병소의 병기가 진행됨에 따라 경부 림프절 전이 빈도도 증가 되며 또한 경부 림프절의 병기도 증가되는 것을 관찰 할 수 있었다.

• 동의생리병리학회지
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• 제27권6호
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• pp.782-788
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• 2013

Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae), colloquially known "Gujulcho" in Korea, has been used in traditional medicine for the treatment of various diseases, including cough, common cold, bladder-related disorders, gastroenteric disorders, hypertension, and inflammatory diseases, such as pneumonia, bronchitis, pharyngitis, and rheumatoid arthritis (RA) However, the effect of Chrysanthemum zawadskii var. latilobum on breast cancer invasion is unknown. In this study, we investigated the inhibitory effect of Chrysanthemum zawadskii var. latilobum extract (CZE) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-9 (MMP-9) expression and cell invasion, as well as the molecular mechanisms involved in MCF-7 cells. CZE were not cytotoxic up to 100 ${\mu}g/ml$ concentration in the MCF-7 cell line. CZE decreased MMP-9 expression. TPA substantially increased NF-${\kappa}B$ DNA binding activity. Pre-treatment with CZE inhibited TPA-stimulated NF-${\kappa}B$ binding activity and NF-${\kappa}B$ related protein expression. To identify invasion ability of MCF-7 cells decreased by CZE, we used martrigel invasion assay. As a result, it is significantly decreased cell invasion. These results indicate that CZE-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the NF-${\kappa}B$ pathway in MCF-7 cells. Chrysanthemum zawadskii var. latilobum may have potential value in restricting breast cancer metastasis.

• Journal of Oral Medicine and Pain
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• 제36권1호
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• pp.11-20
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• 2011

Valproic acid(VPA)는 아주 잘 알려진 항경련제로서, 30년 동안 간질치료제로서 사용되어져 왔다. VPA는 1997년에 최초로 항암제의 효능이 밝혀졌으며, VPA의 항암효과는 히스톤탈아세틸화효소 억제제의 기전에 기인한다고 규명되었다. 17AAG(17-Allyamnio-17-demethoxygeldanamycin)는 HSP90의 억제제이며, HSP90은 세포증식과 세포생존에 관여하며, 최근 17AAG가 세포자멸사를 유도한다는 연구들이 보고되어지고 있다. 본 연구는 히스톤탈아세틸화효소억제제인 VPA와 HSP90 억제제인 17AAG의 병용처리가 사람골육종세포에 상승 세포자멸사 효과가 있는지를 알기 위해서 수행되었다. VPA과 17AAG의 병용처리가 단독처리에 비해서 효과적인 세포생존율 감소가 있는지 확인하기 위해서 trypan-blue법을 시행하였고, 세포자멸사의 유도와 증가를 확인하기 위해서 Hoechst 염색법, flow cytometry(DNA hypoploidy와 MMP 측정), Western bot 분석법 그리고 면역형광염색법을 수행하였다. 병용처리 된 사람골육종세포는 단독처리 된 사람골육종세포에서 거의 관찰할 수 없었던 핵 응축과 조각남, 사립체막 전위와 DNA 양의 감소, cytochrome c의 세포질로의 유리, AIF의 핵으로의 이동, caspase-3과 caspase-7의 파괴 및 PARP의 분절화와 같은 세포자멸사 증거를 보였다. 48시간 동안 1 mM의 VPA와 0.5 ${\mu}M$ 17AAG을 각기 단독처리 한 결과에서는 세포자멸사를 유도 못했으나, 병용처리한 결과에는 아주 탁월한 세포자멸사의 유도를 보였다. 이러한 병용처리 결과는 사람골육종의 새로운 치료적 전략으로 응용될 수 있다고 생각한다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4469-4475
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• 2012

Background: The potential use of hypomethylation of Long INterspersed Element 1 (LINE-1) and Alu elements (Alu) as a biomarker has been comprehensively assessed in several cancers, including head and neck squamous cell carcinoma (HNSCC). Failure to detect occult metastatic head and neck tumors on radical neck lymph node dissection can affect the therapeutic measures taken. Objective: The aim of this study was to investigate the LINE-1 and Alu methylation status and determine whether it can be applied for detection of occult metastatic tumors in HNSCC cases. Methods: We used the Combine Bisulfite Restriction Analysis (COBRA) technique to analyse LINE-1 and Alu methylation status. In addition to the methylation level, LINE-1 and Alu loci were classified based on the methylation statuses of two CpG dinucleotides in each allele as follows: hypermethylation ($^mC^mC$), hypomethylation ($^uC^uC$), and 2 forms of partial methylation ($^mC^uC$ and $^uC^mC$). Sixty-one lymph nodes were divided into 3 groups: 1) non-metastatic head and neck cancer (NM), 2) histologically negative for tumor cells of cases with metastatic head and neck cancer (LN), and 3) histologically positive for tumor cells (LP). Results: Alu methylation change was not significant. However, LINE-1 methylation of both LN and LP was altered, as demonstrated by the lower LINE-1 methylation levels (p<0.001), higher percentage of $^mC^uC$ (p<0.01), lower percentage of $^uC^mC$ (p<0.001) and higher percentage of $^uC^uC$ (p<0.001). Using receiver operating characteristic (ROC) curve analysis, $%^uC^mC$ and $%^mC^uC$ values revealed a high level of AUC at 0.806 and 0.716, respectively, in distinguishing LN from NM. Conclusion: The LINE-1 methylation changes in LN have the same pattern as that in LP. This epigenomic change may be due to the presence of occult metastatic tumor in LN cases.

• Journal of Ginseng Research
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• 제32권1호
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• pp.19-25
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• 2008

인삼의 지용성 성분을 2개월 및 6개월 동안 암환자에게 복용시킨 결과, 인삼의 지용성 성분은 CD4/CD8 비율과 자연살해세포의 수를 정상적으로 유지시킴으로써 암환자의 면역기능 유지에 효과가 있음을 보여주었다. 인삼의 지용성 성분을 2개월간 투여한 실험군의 87.5%에서, 6개월간 투여한 실험군의50%에서 암환자의 종양수치가 낮아지거나 정상범위에서 안정하게 유지되는 긍정적인 효과가 나타났다. 인삼의 지용성 성분을 6개월간 투여한 실험군에서 간 기능을 나타내는 GOT,GPT 및 ALP 수치와 신장 기능을 나타내는 BUN과 creatinine수치도 역시 정상 범위로 유지되어 인삼의 지용성 성분의 장기 복용이 간과 신장 기능에 긍정적인 효과를 가짐을 확인하였다. 따라서 인삼의 지용성 성분이 암환자들의 면역성 강화,간·신장 기능을 유지 및 개선시켜 건강에 도움을 주는 것으로 평가됨으로써 인삼의 지용성 성분을 암환자의 식이 및 항암보조제로서 적용할 수 있는 가능성을 제시하였다. 이러한결과는 비록 통계학적인 유의성은 없지만 본격적인 임상실험의 수행을 위한 기초 자료로서 충분한 가치를 가지므로, 이를바탕으로 대단위 개체를 대상으로 하는 본격적인 추가 임상실험 연구를 수행하여 인삼의 지용성 성분이 암환자의 항암및 면역기능 강화에 효과가 있음을 임상적으로 증명할 수 있을 것으로 기대한다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1255-1258
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• 2015

Background: Locally advanced head and neck cancer is generally incurable and has a short survival rate. This study aimed to evaluate symptom relief, disease response, and acute toxicity after palliative hypo-fractionated radiotherapy and long-term survival in affected patients. Materials and Methods: Between January 2011 to December 2011, 80 patients who were histopathologically diagnosed as having stage III or stage IV head and neck squamous cell carcinoma based on Eastern Cooperative Oncology Group (ECOG) performance status 1-3, were offered palliative radiotherapy (20 Gy/5Fr/5 Days). Later these patients were evaluated on 30th day after completion of treatment for disease response based on World Health Organisation (WHO) criteria and palliation of symptoms using symptomatic response grading and acute toxicities by the Radiation Therapy Oncology Group (RTOG). Many patients were given post radiation therapy (RT) palliative chemotherapy for appropriate palliative care and a few patients were selected for further curative RT. The overall survival was also evaluated among this group of patients with last follow up date of 1st May, 2014. Results: The most common presenting complaint was pain followed by dysphagia. Most patients (60-70%) had appreciable relief in their presenting symptoms. A good response was observed in the majority following palliative RT; a few patients had progressive disease and some had stable and regressed disease. None of the patients experienced radiation toxicity that required hospital admission. Almost all showed grade one and two acute skin and mucosal toxicity one month after completion of treatment. The mean survival days for patients given only hypofractionated palliative RT was 307 days, those with post palliative RT and palliative chemotherapy was 390 days and patients who went on to receive further palliative RT and curative RT dose had significantly overall survival of 582 days. Conclusions: Advanced head and neck cancer should be identified for suitable palliative hypofractionated radiotherapy to achieve acceptable symptom relief in a great proportion of patients and should be followed by palliative chemotherapy or curative RT in suitable cases for long-term symptom-free survival.