• 대한세포병리학회지
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• 제1권1호
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• pp.111-120
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• 1990

Small cell neuroendocrine carcinoma of the uterine cervix is a distinct subtype of cervical cancer that appears analogous to oat cell carcinoma and carcinoid tumors of the lung. It has been assumed to be derived from the neural crest via argyrophilic cells in the normal endocervix. We have recently encountered a case of small cell neuroendocrine carcinoma of the uterine cervix coexisting with adenocarcinoma which was argyrophil negative. A 66-year-old multiparous woman was admitted because of vaginal bleeding for 2 months. Cervicovaginal smear revealed several scattered clusters and sheets of monotonous small cells with some peripheral palisading in the background of hemorrhage and necrosis. Radical hysterectomy specimen revealed an ulcerofungating tumor on endocervical canal which was composed of two components. Major component of the tumor was made up of monomorphic population of small oval-shaped tumor cells arranged in sheets and partly in acinar structures or trabecular fashion. Other component was adenocarcinoma, endocervical well-differentiated type. Argyrophilia was present on the Grimelius stain and immunohistochemical studies revealed diffuse positivity to neuron-specific enolase and carcinoembryonic antigen. Electron microscopic examination showed clusters of small round to oval cells, which had a few well-formed desmosomes and several membrane-bound, dense-core neurosectetory granules.

• Journal of Radiation Protection and Research
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• 제43권2호
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• pp.66-74
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• 2018

Background: Tumor response to anticancer therapies can much be influenced by microenvironmental factors. In this study, we determined the effect of these microenvironmental factors on DNA methylation using A549 human lung adenocarcinoma cell line. Materials and Methods: We subjected A549 cells to various conditions mimicking tumor microenvironment including hypoxia, acidosis (sodium lactate), oxidative stress ($H_2O_2$), bystander effect (supernatant from doxorubicin (Dox)-treated or irradiated cells), and immune cell infiltration (supernatant from THP-1 or Jurkat T cells). Genomic DNA was isolated from these cells and analyzed for DNA methylation. Clonogenic cell survival, gene expression, and metabolism were analyzed in cells treated with some of these conditions. Results and Discussion: We found that DNA methylation level was significantly decreased in A549 cells treated with conditioned media from Dox-treated cells or Jurkat T cells, or sodium lactate, indicating an active transcription. To determine whether the decreased DNA methylation affects radiation sensitivity, we exposed cells to these conditions followed by 6 Gy irradiation and found that cell survival was significantly increased by sodium lactate while it was decreased by conditioned media from Dox-treated cells. We further observed that cells treated with conditioned media from Dox-treated cells exhibited significant changes in expression of genes including BAX and FAS (involved in apoptosis), NADPH dehydrogenase (mitochondria), EGFR (cellular survival) and RAD51 (DNA damage repair) while sodium lactate increased cellular metabolism rather than changing the gene expression. Conclusion: Our results suggest that various tumor microenvironmental factors can differentially influence DNA methylation and hence radiosensitivity and gene expression in A549 cancer cells.

• Tuberculosis and Respiratory Diseases
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• 제45권2호
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• pp.290-300
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• 1998

연구배경: CYFRA 21-1은 기관지 상피 세포에 혼재하는 cytokeratin 19 분절을 검출하는 종양표지자로서, 폐암 특히 편평 상피 세포암에 많이 발현되는 것으로 알려져 있다. 그러나 양성 폐질환중 폐실질의 손상이 심한 폐결핵 환자에서도 혈중 CYFRA 21-1 의 측정치가 진단 양성 기준치 보다 높을 경우 이 검사법의 특이도는 감소되며, 폐암이 동반된 결핵환자에서 CYFRA 21-1 이 폐암 진단에 보조적 검사법이 될 수 없을 것이다. 이에 저자는 CYFRA 21-1 의 측정이 폐암이 동반된 폐결핵환자에서 폐암진단에 유용한 검사법이 될 수 있을지를 알아보기 위하여 본 연구를 시행하였다. 방 법: 20명의 정상인과 25명의 폐암 환자를 대조군으로하고, 81명의 폐결핵 환자를 대상으로 객담 결핵균 도말 검사, 흉부 방사선 소견 및 과거 치료력에 따른 혈중 CYFRA 21-1의 농도 변화를 면역 방사 계수법으로 측정, 비교 분석하여 다음과 같은 결과를 얻었다. 결 과: 폐결핵 환자에서 혈중 CYFRA 21-1의 측정치는 $1.54{\pm}1.19ng/mL$로 폐암 환자의 $12.25{\pm}15.97ng/m$에 비하여 유의하게 낮았으며 (p<0.01), 정상인의 $0.90{\pm}0.49ng/mL$ 보다는 약간 높았으나 유의한 차이는 없었다. 폐결핵환자에서 혈중 CYFRA 21-1 의 측정치가 진단양성 기준치 3.3 ng/mL 이하인 경우는 77명(95%)이었고, 폐암 환자중 측정치가 진단 양성기준치 이상인 경우는 16명(64%)이었다. 객담내 결핵균 도말 검사에 따른 혈중 CYFRA 21-1 의 측정치는 음성인 환자가 $1.72{\pm}1.45ng/mL$로 양성인 환자의 $1.33{\pm}0.79ng/mL$ 보다 높았으나 유의한 차이는 없었다. 흉부 방사선 소견에 따른 혈중 CYFRA 21-1의 측정치는 결핵성 폐 침윤만 있는 환자가 $2.15{\pm}1.63ng/mL$로 폐 허탈이 동반된 환자의 $1.04{\pm}0.54ng/mL$에 비하여 유의하게 높았으며 (p<0.01), 공동 및 폐 허탈의 크기가 클수록 측정치가 유의하게 낮았다(p<0.05). 초치료 환자에서 혈중 CYFRA 21-1의 측정치는 $1.91{\pm}1.55ng/mL$로 난치성 환자의 $0.92{\pm}0.30ng/mL$에 비하여 유의하게 높았다 (p<0.05). 결 론: 폐실질의 손상이 심한 초기 침윤성 병변을 가진 초치료 폐결핵 환자에서 혈중 CYFRA 21-1 의 측정치가 높았으나 측정치의 대부분이(95%) 진단 양성 기준치 이하였음으로, 폐암이 동반된 폐결핵 환자에서도 CYFRA 21-1 의 측정이 폐암의 진단에 보조적 검사법이 될 수 있을 것으로 생각한다.

• 대한한방내과학회지
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• 제33권4호
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• pp.405-417
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• 2012

목 적 : 본 연구에서는 생강나무 메탄올 추출물이 암전이 억제에 미치는 영향을 조사하고자 하였다. 방 법 : 생강나무 추출물의 암전이 억제능을 확인하기 위해서 B16F10 흑색종 세포를 이용하여 금속단백분해효소의 활성 및 발현을 측정하였으며, 암세포의 이동능이나 침윤능도 조사하였다. 폐전이 동물모델에서 생강나무 추출물이 미치는 영향을 조사하여 활성을 최종적으로 확인하였다. 결 과 : 1. 생강나무 추출물은 B16F10 흑색종 세포에서 뚜렷한 금속단백분해효소의 효소활성 및 발현 억제효과를 보였으며 이는 NF-${\kappa}B$의 활성 억제에서 기인한 것임을 확인하였다. 2. 흑색종 세포의 이동이나 침윤 역시 생강나무 추출물 투여에 의해 현저히 감소하였다. 3. 폐전이 동물 모델에서도 생강나무 추출물에 의해 폐로 전이되 집락의 수가 감소하였다. 결 론 : 이상의 결과로 생강나무 추출물은 뛰어난 암전이 억제효과가 있는 것을 확인할 수 있었으며, 전이성 암치료에 있어서 유용하게 사용될 수 있을 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제42권6호
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• pp.846-854
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• 1995

연구배경: Cyfra 21-1은 상피종양세포의 세포질에 존재하는 cytokeratin 19의 분절로서 상피종양세포의 파괴시 혈중내로 유리되므로 그 혈중 농도를 측정하여 종양표지자로 이용할 수 있는 것으로 알려져 있다. 이에 저자들은 폐암, 폐결핵, 기타폐질환 및 정상대조군 환자들의 혈청내 Cyfra 21-1, SCC 항원 및 CEA의 농도를 측정하여 폐암의 종양표지자로서 Cyfra 21-1과 SCC 항원 및 CEA의 진단적 효용성을 비교 관찰하고자 하였다. 또한 편평상피세포암에서 Cyfra 21-1과 평상펴셰포암의 특이 종양표지자로 알려진 SCC 항원과의 진단적 민감도와 특이도의 차이를 비교하고 그 병기 진행에 따른 Cyfra 21-1의 혈중농도의 증가 여부를 관찰하고자 하였다. 방법: 1992년 12월부터 1993년 6월까지 서울중앙병원에 입원하여 조직생검으로 초진단된 원발성 폐암 79예(편평상피세포암 41예, 선암 18예, 기타의 미분화 비소세포양 14예, 소세포암 6예)와 폐결핵 32예, 기타폐질환 23예, 정상대조군 23예를 대상으로 하였다. Cyfra 21-1과 ELSA2-CEA를 사용하였고, SCC 항원은 방사계수측정 kit인 ABBOTT SCC RIABEAD를 사용하였다. 결과: 1) Cyfra 21-1의 혈중농도는폐암군이 평균({\pm}표준편차) $18.38{\pm}3.65\;ng/mL$로서 비교군 $1.16{\pm}0.53\;ng/mL$보다 유의하게 높았다(p<0.0001). SCC 항원은 폐암군에서 $3.53{\pm}6.06\;ng/mL$로서 비교군 $1.19{\pm}0.5\;ng/mL$보다 유의하게 높았다(p<0.01). CEA는 폐암군에서 $35.03{\pm}13.9\;ng/mL$로서 비교군 $2.89{\pm}1.01\;ng/mL$ 보다 유의하게 높았다(p<0.0001). 2) 폐암군내에서는 Cyfra 21-1의 혈중농도가 편평상 피세포암군에서 $31.52{\pm}40.13\;ng/mL$로서 선암군 $2.41{\pm}1.34\;ng/mL$(p<0.0001) 및 소세포암군 $2.15{\pm}2.05\;ng/mL$(p=0.007) 보다 유의하게 높았다. SCC 항원의 혈중농도는 편평상피세포암군에서 $5.1{\pm}7.68\;ng/mL$로서 선암군 $1.36{\pm}0.69\;ng/mL$(p=0.009) 및 소세포암군 $1.1{\pm}0.24\;ng/mL$(p=0.024)보다 유의하게 높았다. 3) 편평상피세포암군에서 폐암의 병기 진행에 따른 Cyfra 21-1의 혈중농도의 증가는 없었다. 4) Cyfra 21-1의 진단양성 기준치를 3.3 ng/mL로 하였을때 편평상피세포암의 민감도가 83%로 선암의 22%, 소세포암의 17%보다 높게 산출되었다. SCC 항원의 민감도가 편평상피세포암에서 39%, 선암에서 11%, 소세포암에서 0% 이었다. CEA의 민감도가 편평상피세포암에서 20%, 선암에서 39%, 소세포암에서 33%이었다. 5) ROC 곡선 분석상 폐암의 진단에서 Cyfra 21-1의 민감도와 특이도가 SCC 항원 및 CEA 보다 우수한 것으로 나타났다. 결론: Cyfra 21-1은 폐임에서 SCC 항원 및 CEA에 비하여 민감도 및 특이도가 높은 종양표지자이며, 특히 편평상피세포암에서 그 민감도와 특이도가 높아 편평상피세포암의 특이 종양표지자로 알려진 SCC 항원보다 우수한 종양표지자로 사료되었다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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• pp.4331-4338
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• 2014

$N^1$-(2, 5-dimethoxyphenyl)-$N^8$-hydroxyoctanediamide (N25) is a novel SAHA cap derivative of HDACi, with a patent (No. CN 103159646). This invention is a hydroxamic acid compound with a structural formula of $RNHCO(CH_2)6CONHOH$ (wherein R=2, 5dimethoxyaniline), a pharmaceutically acceptable salt which is soluble. In the present study, we investigated the effects of N25 with regard to drug distribution and molecular docking, and anti-proliferation, apoptosis, cell cycling, and $LD_{50}$. First, we designed a molecular approach for modeling selected SAHA derivatives based on available structural information regarding human HDAC8 in complex with SAHA (PDB code 1T69). N25 was found to be stabilized by direct interaction with the HDAC8. Anti-proliferative activity was observed in human glioma U251, U87, T98G cells and human lung cancer H460, A549, H1299 cells at moderate concentrations ($0.5-30{\mu}M$). Compared with SAHA, N25 displayed an increased antitumor activity in U251 and H460 cells. We further analyzed cell death mechanisms activated by N25 in U251 and H460 cells. N25 significantly increased acetylation of Histone 3 and inhibited HDAC4. On RT-PCR analysis, N25 increased the mRNA levels of p21, however, decreased the levels of p53. These resulted in promotion of apoptosis, inducing G0/G1 arrest in U251 cells and G2/M arrest in H460 cells in a time-dependent and dose-dependent manner. In addition, N25 was able to distribute to brain tissue through the blood-brain barrier of mice ($LD_{50}$: 240.840mg/kg). In conclusion, our findings demonstrate that N25 will provide an invaluable tool to investigate the molecular mechanism with potential chemotherapeutic value in several malignancies, especially human glioma.

• 통합자연과학논문집
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• 제16권3호
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• pp.81-95
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• 2023

Colorectal cancer is one of the most common types of cancer worldwide, ranking third after lung and breast cancer in terms of global prevalence. With an expected 1.93 million new cases and 935,000 deaths in 2020, it is more prevalent in males than in women. Evidence has shown that during the later stages of colon cancer, STAT1 promotes tumor progression by promoting cell survival and resistance to chemotherapy. Recent studies have shown that inhibiting STAT1 pathway leads to a reduction in tumor cell proliferation and growth, and can also promote apoptosis in colon cancer cells. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened FDA database against STAT1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top 10 compounds to be more specific with STAT1 comparing the affinity with STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. The drugs that showed higher affinity were subjected to Conceptual - Density functional theory. Besides, the Molecular dynamic simulation was also carried out for the selected leads. We also validated in-vitro against colon cancer cell lines. The results showed mainly Acetyldigitoxin has shown better binding to the target. From this study, we can predict that the drug Acetyldigitoxin has shown noticeable inhibitory efficiency against STAT1, which in turn can also lead to the reduction of tumor cell growth in colon cancer.

• Journal of Pharmaceutical Investigation
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• 제33권2호
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• pp.105-112
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• 2003

Selective COX (cyclooxygenase)-2 inhibitors including celecoxib have been shown to induce apoptosis and cell cycle changes in various tumor cells. New inhibitors are recently being developed as chemomodulating agents. We evaluated celecoxib and screened 150 synthetic compounds for anti-proliferative activities in vitro. Effects of celecoxib on COX activity, cell growth, cell cycle distribution, and apoptosis induction were determined in A549 COX-2 overexpressing human non-small cell lung cancer (NSCLC) cells. The COX inhibition of celecoxib increased with concentration up to 82% at $1\;{\mu}M$ after 24 hr exposure. Forty ${\mu}M$ and $50\;{\mu}M$ of ce1ecoxib induced $G_1$ arrest, and TUNEL-positive apoptotic cells, respectively. Among 150 compounds, several compounds were selected for having greater COX-2 inhibitory activity and higher selectivity than celecoxib with growth inhibitory activity. Celecoxib showed concentration-dependent COX inhibitory activity, and ability to induce cell cycle arrest and apoptosis in human NSCLC cells in vitro. Among synthetic analogues screened, several compounds showed promising in vitro activity as COX-2 inhibitory anticancer agents, which warrant further evaluation in vitro and in vivo.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8203-8210
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• 2016

Adenocarcinomas (AC) are the most frequently encountered carcinomas. It may be quite challenging to detect the primary origin when those carcinomas metastasize and the first finding is a metastatic tumor. This study evaluated the role of sex hormone binding globulin (SHBG) positivity in tumor cells in the subclassification and detection of the original organ of adenocarcinomas. Between 1994 and 2008, 64 sections of normal tissue belonging to ten organs, and 116 cases diagnosed as adenoid cystic carcinoma and mucoepidermoid carcinoma of the salivary gland, lung adenocarcinoma, invasive ductal carcinoma of the breast, adenocarcinoma of stomach, colon, gallbladder, pancreas and prostate, endometrial adenocarcinoma and serous adenocarcinoma and mucinous adenocarcinoma of the ovary, were sent to the laboratory at the Department of Pathology at the Yuzuncu Yil University School of Medicine, where they were stained immunohistochemically, using antibodies against SHBG. The SHBG immunoreactivity in both the tumor cells and normal cells, together with the type, diffuseness and intensity of the staining were then evaluated. In the differential diagnosis of the adenocarcinomas of the organs, including the glandular structures, impressively valuable results are encountered in the tumor cells, whether the SHBG immunopositivity is evaluated alone or together with other IHC markers. Further extensive research with a larger number of cases, including instances of cholangiocarcinoma and cervix uteri AC [which we could not include in the study for technical reasons] should be performed, in order to appropriately evaluate the role of SHBG in the differential diagnosis of AC.

• 대한한방내과학회지
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• 제37권1호
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• pp.16-25
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• 2016

Objectives: Gilgyung-tang (GGT) has been used as one of the main multi-herb formulas to treat “Peo-ong” (lung abscess). In this study, we investigated the inhibitory effects of water extracts of GGT on cell migration and invasion, two critical cellular processes that are often deregulated during metastasis, in human bladder cancer 5637 cells.Methods: Effects on cell viability were quantified using an MTT assay. To analyze the anti-metastatic effects, we conducted a wound healing migration assay, an in vitro invasiveness assay, and a measurement of the transepithelial electrical resistance (TER). The expression of protein and mRNA were measured by Western blotting and real-time polymerase chain reaction (RT-PCR), respectively.Results: GGT markedly inhibited the cell motility and invasiveness of 5637 cells within the concentration range that was not cytotoxic. The inhibitory effects of GGT on cell invasiveness were associated with tightening of the tight junctions (TJs), which was demonstrated by an increase in the TER. The RT-PCR and Western blotting results indicated that GGT decreased the levels of claudin proteins. GGT also inhibited the activity and expression of matrix metalloproteinase (MMP)-2 and -9 and simultaneously increased the levels of tissue inhibitor of metalloproteinase-1 and -2.Conclusions: Our findings suggest that GGT reduces both the migration and the invasion of 5637 cells by modulating the activity of TJs and MMPs.