• Gut and Liver
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• 제12권6호
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• pp.728-735
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• 2018

Background/Aims: The combination of nab-paclitaxel and gemcitabine (nab-P/Gem) is widely used for treating metastatic pancreatic cancer (MPC). We aimed to evaluate the therapeutic outcomes and prognostic role of treatment-related peripheral neuropathy in patients with MPC treated with nab-P/Gem in clinical practice. Methods: MPC patients treated with nab-P/Gem as the first-line chemotherapy were included. All 88 Korean patients underwent at least two cycles of nab-P/Gem combination chemotherapy (125 and $1,000mg/m^2$, respectively). Treatment-related adverse events were monitored through periodic follow-ups. Overall survival and progression-free survival were estimated by the Kaplan-Meier method, and the Cox proportional hazards regression linear model was applied to assess prognostic factors. To evaluate the prognostic value of treatment-related peripheral neuropathy, the landmark point analysis was used. Results: Patients underwent a mean of $6.7{\pm}4.2$ cycles during $6.3{\pm}4.4$ months. The median overall survival and progression-free survival rates were 14.2 months (95% confidence interval [CI], 11.8 to 20.3 months) and 8.4 months (95% CI, 7.1 to 13.2 months), respectively. The disease control rate was 84.1%; a partial response and stable disease were achieved in 30 (34.1%) and 44 (50.0%) patients, respectively. Treatment-related peripheral neuropathy developed in 52 patients (59.1%), and 13 (14.8%) and 16 (18.2%) patients experienced grades 2 and 3 neuropathy, respectively. In the landmark model, at 6 months, treatment-related peripheral neuropathy did not have a significant correlation with survival (p=0.089). Conclusions: Nab-P/Gem is a reasonable choice for treating MPC, as it shows a considerable disease control rate while the treatment-related peripheral neuropathy was tolerable. The prognostic role of treatment-related neuropathy was limited.

• Advances in pediatric surgery
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• 제11권1호
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• pp.46-52
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• 2005

Solid and papillary epithelial neoplasm (SPEN) of the pancreas is a rare tumor with low malignant potentiality that usually occurs in young females. Preoperative evaluation, especially radiologic tests, including ultrasonography and CT scan, is helpful in the diagnosis. These studies demonstrate a well-demarcated large mass with solid and cystic portions, frequently in the tail or body of the pancreas. Complete resection is usually curative, however local invasion and/or metastasis may occur. The authors report a case of a solid and papillary epithelial neoplasm of the pancreatic body in a 14-year old child at St. Benedict Hospital and review the literature.

• Journal of Gastric Cancer
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• 제5권4호
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• pp.252-259
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• 2005

위에 발생하는 원발성 소세포암은 매우 드물며 예후는 좋지 않아 초기에 발견되어도 60% 이상이 1년 이내에 사망한다. 본원 외과에서 수술치료를 받은 위소세포암 첫 번째 증례는 수술소견상 복막전이 소견 등으로 근치적 수술이 불가능하여 위공장문합술을 시행하였다. 수술 후 etoposide, cisplatin화학요법을 시행하고 6개월 뒤에 찍은 CT촬영상 복막전이, 림프절전이가 악화되어 paclitaxel, cisplatin으로 약제변경 하였으나 수술 후 14개월째 사망하였다. 두 번째 증례는 내시경 조직검사상 위선암과 소세포암의 복합 소견을 보였으며 CT 촬영상 복강동맥주위 림프절종대 및 간전이 소견이 발견되었다. TS-1과 cisplatin 선행화학요법 2차 시행 후 림프절 종대는 완전관해, 원발소 및 간전이소는 부분관해 소견을 보여 위전절제술 및 확대림프절 절제술을 시행하였다. 수술로 절제된 위 및 주변 림프절 35개의 조직검사상 암세포가 모두 사멸되었으며 위내 원 발병소는 심한 심유화변성 소견을 보여 수술 전 사용한 항암요법이 유의했다고 판단되었다. 이에 수술 후에도 동일 제제로 4차례 추가 투약을 하였다. 수술 후 6개월에 시행한 CT촬영상 간전이가 진행된 소견을 보여 간우엽 후부절제술을 시행하고 이후 ininotecan과 cisplatin을 이용한 항암화학요법을 5차례 시행하고 있으며 술 후 14개월째 생존 중이다. 세 번째 증례는 순수 소세포암으로 근치적 위아전절제술을 시행하였으며 수술 후 5차례에 걸쳐 TS-1, cisplatin 보조항암화학요법 시행하였고 수술 후 13개월째 재발 없이 생존 중이다.

• Journal of Gastric Cancer
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• 제7권2호
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• pp.74-81
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• 2007

목적: 위암이 국소적으로 진행하여 췌장과 비장으로 직접 침윤이 발생되었을 췌-비장 절제를 시행하는 것에는 반대 의견이 없지만, 췌-비장의 보존이 가능함에도 불구하고, 비장혈관이나 비문부 림프절의 완전 절제를 위해서 췌-비장 절제가 시행되는 것은 논란의 여지가 많다 저자들은 위 중-상부의 진행암으로 위 전절제술과 함께 원위부 췌-비장 절제가 시행되었던 환자들의 수술 결과 분석을 통하여 불필요한 합병절제를 피할 수 있는 방법을 찾고자 하였다. 대상 및 방법: 1990년부터 2001년까지 가톨릭대학교 의과대학 외과학교실에서 위 전절제술과 동반되어 원위부 췌-비장 절제가 시행된 118명의 환자 중, 병리 조직학적으로 암의 췌장 침윤이 없었던 90예(I군)와 침윤이 확인된 28예(II군)의 임상병리학적 특성, 이환율과 사망률 및 생존율 등을 후향적으로 분석하였다. 결과: 전체 118예 중 췌장 침윤이 확인된 pT4는 28예(23.7%)였고, 침윤이 없었던 pT3과 pT2가 각각 65예(55.1%) 와 20예(16.9%)였으며, pT1도 5예(4.3%)였다. 병기는 28예의 pT4 중에서 림프절 전이가 있어 IV기인 경우가 25예(89.3%)였고, 림프절 전이가 없는 IIIa기는 3예(10.7%)에 불과하였다. 또한 I군은 la (pT1N0)기 4예, Ib (pT2N0)기 7예였고, II기는 pT2N1 8예, pT3N0 12예, pT1N2 1예였으며, III기는 IIIa 15예, IIIb 17예, IV기는 26예였다. 두 군의 임상병리학적 특성 중 병기, 절제연 및 근치도에서 유의한 차이를 보였고, 생존에 영향을 미치는 인자들의 단변량 분석에서는 병기, 위벽 침윤, 췌장 침윤, 림프절전이, 비장혈관과 비문부 림프절 전이, 전이 림프절 비율, 근치도, 간 및 복막 전이 등에서 유의한 차이를 보였으며, 이 중 병기와 전이 림프절 비율 및 근치도가 예후에 영향을 미치는 독립적 예후인자로 나타났다. 5년 생존율은 I군이 36.2%, II군이 13.9%였고, 술 후 합병증으로 췌장 루 6예(5.1%), 복강 내 농양 5예(4.2%), 출혈 5예(4.2%)로 수술로 인한 전체 이환율은 22.1%였으며, 사망률은 6.8% (8예)였다. 결론: 진행성 상부 위암으로 위 전 절제술을 시행할 때 원위부 췌-비장 절제는 이환율이 비교적 높은 술식이기 때문에 간이나 복막전이가 없는 상태에서 위암의 병기가 높고, 절제연이 불충분하며, 근치적 절제가 불가능하다고 판단될 때에만 선택적으로 시행되는 것이 좋다고 생각한다.

• Biomolecules & Therapeutics
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• 제21권5호
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• pp.338-342
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• 2013

Sphingosylphosphorylcholine (SPC) is significantly increased in the malicious ascites of tumor patients and induces perinuclear reorganization of keratin 8 (K8) filaments in PANC-1 cells. The reorganization contributes to the viscoelasticity of metastatic cancer cells resulting in increased migration. Recently, we reported that transglutaminase-2 (Tgase-2) is involved in SPC-induced K8 phosphorylation and reorganization. However, effects of Tgase-2 inhibitors on SPC-induced K8 phosphorylation and reorganization were not clearly studied. We found that ethacrynic acid (ECA) concentration-dependently inhibited Tgase-2. Therefore, we examined the effects of ECA on SPC-induced K8 phosphorylation and reorganization. ECA concentration-dependently suppressed the SPC-induced phosphorylation and perinuclear reorganization of K8. ECA also suppressed the SPC-induced migration and invasion. SPC induced JNK activation through Tgase-2 expression and ECA suppressed the activation and expression of JNK in PANC-1 cells. These results suggested that ECA might be useful to control Tgase-2 dependent metastasis of cancer cells such as pancreatic cancer and lung cancers.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9523-9527
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• 2014

The incidence of colorectal cancer (CRC) is increasing in many Asian countries and microRNAs have already been proven to be associated with tumorigenesis. Currently, microRNA-376a (miR-376a) expression and association with clinical factors in CRC remains unclear. In this study, real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was carried out on 53 matched pairs of CRC and adjacent normal mucosa to investigate the expression levels of miR-376a. According to the high or low expression of miR-376a, patients were divided into two groups. The relationship between miR-376a expression and clinicopathological factors of 53 patients was evaluated. Survival analysis of 53 CRC patients was performed with clinical follow-up information and survival curves were assessed by the Kaplan-Meier method. Immunohistochemistry (IHC) staining was performed on sections of paraffin-embedded tissue to investigate the vascular endothelial growth factor (VEGF) expression. MiR-376a showed low expression in cancer tissues compared to the adjacent normal tissues and altered high miR-376a expression tended to be positively correlated with advanced lymph node metastasis and shorter patient survival. VEGF IHC positivity was significantly more common in patients with high expression levels of miR-376a.Those results demonstrated that miR-376a may be a meaningful prognostic biomarker and potential therapeutic target in colorectal cancer.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제36권1호
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• pp.1-6
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• 2010

Purpose: Chemokines are structurally related, small polypeptide signaling molecules that bind to and activate a family of transmembrane G protein-coupled receptors, the chemokine receptors. Recently, interaction between the chemokine receptor CXCR4 and its ligand, stromal cell-derived factor 1 (SDF-1 or CXCL12), has been found to play an important role in tumorigenicity, proliferation, metastasis and angiogenesis in many cancers such as lung cancer, breast cancer, melanoma, glioblastoma, pancreatic cancer and cholangiocarcinoma. Hence, the goal of this study is to identify the correlation of clinicopathological factors and the up-regulation of SDF-1 expression in oral squamous cell carcinoma. Material and methods: We studied the immunohistochemical staining of SDF-1, quantitative RT-PCR (qRT-PCR) of SDF-1 gene in 20 specimens of 20 patients with oral squamous cell carcinoma. Results: 1. In the immunohistochemical study of poor differentiated and invasive oral squamous cell carcinoma, the high level staining of SDF-1 was observed. And the correlation between immunohistochemical SDF-1 expression and tumor nodes metastases (TNM) classification of specimens was significant.($x^2$ test, P < 0.05) 2. In the SDF-1 gene qRT-PCR analysis, SDF-1 expression was more in tumor tissue than in carcinoma in situ tissue. Paired-samples analysis determined the difference of SDF-1 mRNA expression level between the cancer tissue and the carcinoma in situ tissue.(Student's t-test, P < 0.05) Conclusion: These findings suggest that up-regulation of the SDF-1 may play a role in progression and invasion of oral squamous cell carcinoma.

• Molecules and Cells
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• 제41권6호
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• pp.591-602
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• 2018

Gastric cancer is the fifth most common type of malignancy worldwide, and the survival rate of patients with advanced-stage gastric cancer is low, even after receiving chemotherapy. Here, we validated neurotensin receptor 1 (NTSR1) as a potential therapeutic target in gastric cancer. We compared NTSR1 expression levels in sixty different gastric cancer-tissue samples and cells, as well as in other cancer cells (lung, breast, pancreatic, and colon), by assessing NTSR1 expression via semi-quantitative real-time reverse transcription polymerase chain reaction, immunocytochemistry and western blot. Following neurotensin (NT) treatment, we analyzed the expression and activity of matrix metalloproteinase-9 (MMP-9) and further determined the effects on cell migration and invasion via wound-healing and transwell assays. Our results revealed that NTSR1 mRNA levels were higher in gastric cancer tissues than non-cancerous tissues. Both of NTSR1 mRNA levels and expression were higher in gastric cancer cell lines relative to levels observed in other cancer-cell lines. Moreover, NT treatment induced MMP-9 expression and activity in all cancer cell lines, which was significantly decreased following treatment with the NTSR1 antagonist SR48692 or small-interfering RNA targeting NTSR1. Furthermore, NT-mediated metastases was confirmed by observing epithelial-mesenchymal transition markers SNAIL and E-cadherin in gastric cancer cells. NT-mediated invasion and migration of gastric cancer cells were reduced by NTSR1 depletion through the Erk signaling. These findings strongly suggested that NTR1 constitutes a potential therapeutic target for the inhibition of gastric cancer invasion and metastasis.

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.473-481
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• 2020

Axl receptor tyrosine kinase has been implicated in cancer progression, invasion, and metastasis in various cancer types. Axl overexpression has been observed in many cancers, and selective inhibitors of Axl, including R428, may be promising therapeutic agents for several human cancers, such as breast, lung, and pancreatic cancers. Here, we examined the cell growth inhibition mediated by R428 and auranofin individually as well as in combination in the human breast cancer cell lines MCF-7 and MDA-MB-231 to identify new advanced combination treatments for human breast cancer. Our data showed that combination therapy with R428 and auranofin markedly inhibited cancer cell proliferation. Isobologram analyses of these cells indicated a clear synergism between R428 and auranofin with a combination index value of 0.73. The combination treatment promoted apoptosis as indicated by caspase 3 activation and poly (ADP-ribose) polymerase cleavage. Cancer cell migration was also significantly inhibited by this combination treatment. Moreover, we found that combination therapy significantly increased the expression level of Bax, a mitochondrial proapoptotic factor, but decreased that of the X-linked inhibitor of apoptosis protein. Furthermore, the suppression of cell viability and induction of Bax expression by the combination treatment were recovered by treatment with N-acetylcysteine. In conclusion, our data demonstrated that combined treatment with R428 and auranofin synergistically induced apoptosis in human breast cancer cells and may thus serve as a novel and valuable approach for cancer therapy.

• 생명과학회지
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• 제26권9호
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• pp.1056-1062
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• 2016

폐암은 전세계적으로 높은 발병율과 사망률을 보이는 암종으로 소세포암종과 비소세포암종으로 구분되어지며, 비소세포암이 75-80%를 차지하고 있다. miR-155의 유전자의 과 발현은 갑상선암, 유방암, 대장암, 자궁 경부암, 췌장선암(PDAC), 폐암 등의 고형암에서 관찰된다. 본 연구에서는 한국인 폐암 환자의 조직에서 특이적으로 발현되는 miRNA의 양상을 양성 폐질환자 와 비교 분석하고, 폐암환자의 임상병리학적 특성과의 상관성을 분석하여 miRNA가 암 진단의 생물표지자로서의 가능성을 조사하여 향후 암의 조기 진단 및 치료, 예후 연구에 기초 자료를 제공하고자 하였다. 파라핀 포매 된 비소세포폐암환자 및 양성 폐 질환자의 블록에서 total RN를의 분리하여, 정량 실시간연쇄중합반응을 통해 miR-155의 발현량을 정량 분석을 실시하였으며, miR-155의 발현과 폐암환자의 임상적 특징과의 상관관계를 분석하였다. 폐암 환자군과 양성 폐질환자의 miR-155의 △Ct 값을 분석한 결과 폐암환자군에서 유의하게 높게 발현되었다(p<0.001). 병리조직학적 분류에 따라서는 편평상피세포암종에서 선암종에 비해 높게 발현되었다. 분화도에 따라서는 저분화 암에서 고분화암에 비해 유의하게 높게 발현되었다(p=<0.001). 또한 miR-155의 과발현은 림프절 전이와도 통계적으로 유의성 나타내었다(p<0.05). 생존분석결과 miR-155의 과발현은 폐암환자의 생존률과 유의한 상관관계를 나타내었다(p<0.05). 본 연구의 결과로 miR-155의 발현은 폐암의 진행 및 전이에 중요한 역할을 할 것으로 생각되며, 폐암의 조기진단과 예후의 예측을 위하여 보다 다양한 종류의 miRNAs에 대한 연구가 이루어져야 할 것으로 판단된다.