• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1363-1367
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• 2014

This research was conducted to compare differences in colon cancer lymphatic vessel invasion (LVI) with D2-40 antibody labeling and regular HE staining, blood vessel invasion (BVI) with CD34 antibody labeling and HE staining and to assess the possibility of using D2-40-LVI/CD34-BVI in combination for predicting stage II colon cancer prognosis and guiding adjuvant chemotherapy.Anti-D2-40 and anti-CD34 antibodies were applied to tissue samples of 220 cases of stage II colon cancer to label lymphatic vessels and small blood vessels, respectively. LVI and BVI were assessed and multivariate COX regression analysis was performed for associations with colon cancer prognosis. Regular HE staining proved unable to differentiate lymphatic vessels from blood vessels, while D2-40 selectively labeled lymphatic endothelial cell cytosol and CD34 was widely expressed in large and small blood vessels of tumors as well as normal tissues. Compared to regular HE staining, D2-40-labeling for LVI and CD34-labeling for BVI significantly increased positive rate (22.3% vs 10.0% for LVI, and 19.1% vs 9.1% for BVI). Multivariate analysis indicated that TNM stage, pathology tissue type, post-surgery adjuvant chemotherapy, D2-40-LVI, and CD34-BVI were independent factors affecting whole group colon cancer prognosis, while HE staining-BVI, HE staining-LVI were not significantly related. When CD34-BVI/D2-40-LVI were used in combination for detection, the risk of death for patients with two or one positive results was 5.003 times that in the LVI(-)&BVI(-) group (95% CI 2.365 - 9.679). D2-40 antibody LVI labeling and CD34 antibody BVI labeling have higher specificity and accuracy than regular HE staining and can be used as molecular biological indicators for prognosis prediction and guidance of adjuvant chemotherapy for stage II colon cancer.

• Molecules and Cells
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• v.37 no.12
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• pp.888-898
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• 2014

Pancreatic cancer is one of the most fatal cancers and is associated with limited diagnostic and therapeutic modalities. Currently, gemcitabine is the only effective drug and represents the preferred first-line treatment for chemotherapy. However, a high level of intrinsic or acquired resistance of pancreatic cancer to gemcitabine can contribute to the failure of gemcitabine treatment. To investigate the underlying molecular mechanisms for gemcitabine resistance in pancreatic cancer, we performed label-free quantification of protein expression in intrinsic gemcitabine-resistant and -sensitive human pancreatic adenocarcinoma cell lines using our improved proteomic strategy, combined with filter-aided sample preparation, single-shot liquid chromatography-mass spectrometry, enhanced spectral counting, and a statistical method based on a power law global error model. We identified 1931 proteins and quantified 787 differentially expressed proteins in the BxPC3, PANC-1, and HPDE cell lines. Bioinformatics analysis identified 15 epithelial to mesenchymal transition (EMT) markers and 13 EMT-related proteins that were closely associated with drug resistance were differentially expressed. Interestingly, 8 of these proteins were involved in glutathione and cysteine/methionine metabolism. These results suggest that proteins related to the EMT and glutathione metabolism play important roles in the development of intrinsic gemcitabine resistance by pancreatic cancer cell lines.

• Journal of Gastric Cancer
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• v.3 no.2
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• pp.104-111
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• 2003

Purpose: The prognostic significance of peri-operative serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 determination in patients with gastric cancer has been controversial. This study was performed to evaluate the significance of CEA and CA19-9 as clinical predictors of prognosis. Materials and Methods: The correlations between peri-operative serum CEA/CA19-9 levels and clinicopathologic factors were evaluated retrospectively in gastric cancer patients who had undergone curative surgery during the period from January 1995 to December 1998 at the Department of Surgery, Yonsei University College of Medicine. Results: The positive rates for CEA and CA19-9 were $17.9\%$ and $18.4\%$, respectively. The CEA positivity was related to the depth of invasion (P=0.040), lymph-node metastasis (P=0.000), and stage (P=0.001). The CA19-9 positivity was significantly related to the depth of invasion (P=0.000), lymph-node status (P=0.000), and stage (P=0.000). The positive rate of combined assay of pre-operative CEA and CA19-9 was $30.0\%$ There were statistically significant correlations with stage, depth of invasion, or degree of lymphnode metastasis in the combined assay. The survival rates according to the positivity of CEA and to the positivity of CA19-9 were clearly different (P=0.000). Conclusion: It should be stressed that even a simple blood test prior to surgery could be useful in establishing the depth of invasion, the status of lymph-node involvement, and the prognosis. For improved survival, an aggressive lymphadenectomy and adjuvant chemotherapy should be considered for patients with positive levels of pre-operative CA19- 9.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.3
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• pp.217-222
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• 2007

In the last 5 years the Epidermal Growth Factor Receptor (EGFR) has emerged as one of the most important targets for drug development in oncology. Monoclonal antibodies targeting the external domain of EGFR have been shown to have clinical benefits in colorectal and head and neck cancer when combined with chemotherapy and/or radiation. Also the targeting of the epithelial growth factor receptor (EGFR) kinase domain using the closely related inhibitors gefitinib and erlotinib has generally been ineffective against solid tumors, many of which over express the receptor. We found that there were some differential expressions according to primary antibodies of the EGFR protein which being used as one of the histological tumor markers for non-small cell lung cancer (NSCLC). We also found that there are some differential expressions according to antibodies, the pH of the antigen retrieval (AR) buffer solutions and kinds of enzymes. There were some differential expressions according to the secondary antibodies and the detection systems. We analyzed the correlations between the immunohistochemical expressions of the EGFR protein and the gene mutations of the EGFR. The differences between automatic stainers and manual staining methods were also evaluated.

• Molecular & Cellular Toxicology
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• v.3 no.3
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• pp.165-171
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• 2007

Mitomycin C (MMC), an antitumor antibiotic isolated from Streptomyces caespitosus, is used in chemotherapy of gastric, bladder and colorectal cancer. MMC is activated in vivo to alkylate and crosslink DNA, via G-G interstrand bonds, thereby inhibiting DNA synthesis and transcription. This study investigates gene expression changes in response to MMC treatment in order to elucidate the mechanisms of MMC-induced toxicity. MMC was admistered with single dose (0.32 and 1.6 ${\mu}M$) to TK6 cells. Applied Biosystem's DNA chips were used for identifying the gene expression profile by MMC-induced toxicity. We identified up- or down-regulated 90 genes including cyclin M2, cyclin-dependent kinase inhibitor 1A (p21, cip1), programmed cell death 1, tumor necrosis factor (ligand) superfamily, member 9, et al. The regulated genes by MMC associated with the biological pathways apoptosis signaling pathway. Further characterization of these candidate markers related to the toxicity will be useful to understand the detailed mechanism of action of MMC.

• Journal of Ginseng Research
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• v.45 no.5
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• pp.591-598
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• 2021

Background: Hematopoiesis is the production of blood cells from hematopoietic stem cells (HSCs) that reside in the bone marrow. Cyclophosphamide (CTX) is a chemotherapy drug that suppresses the immune system. Korean Red Ginseng (KRG) and Colla corii asini (CCA) have been traditionally used for boosting the immune system. Methods: HSCs in the bone marrow, and immune cell subtype in splenocytes, PBMCs, and thymocytes were investigated. Serum levels of hematopoietic-related markers were analyzed using ELISA. Protein expression in spleen tissue was analyzed using western blot analysis. Hematoxylin & eosin staining in the femurs of mice were also conducted. Results: The combination of KRG and CCA with a ratio of 3:2 increased HSCs, CD3 and CD8⁺ T cells in the circulation, and CD3 T cells in the spleen. A ratio of 2:3 (KRG:CCA) increased the thymic regulatory T cells and recovered the CD3 T cells in the spleen and circulation while recovering proteins in the JAK-STAT pathway in the spleen. Overall, blood cell population and differentiating factors vital for cell differentiation were also significantly recovered by all combinations especially in ratios of 3:2 and 2:3. Conclusion: A ratio of 3:2 (KRG:CCA) is the most ideal combination as it recovered the HSC population in the bone marrow of mice.

• Journal of Korean Traditional Oncology
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• v.23 no.2
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• pp.1-9
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• 2018

Objectives: This study was aimed to report a patient with metastatic pancreatic cancer treated with modified Bangam-tang and Gunchil-dan in conjunction with gemcitabine. There were better survival-related outcomes compared to gemcitabine alone. Methods: The patient with metastatic pancreatic cancer received gemcitabine as palliative chemotherapy since June 2016 concurrent with modified Bangam-tang and Gunchil-dan since October 2016 to October 2017. To evaluate the effect of treatment, tumor markers (carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA)), Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and overall survival were checked. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: After 12 months with the combination treatment, levels of CA19-9 were decreased from 8747 to 265.7 ng/ml and CEA from 42.2 to 6.5 U/ml. Clinical partial response state was shown until May 2, 2017 and stable disease state was maintained from August 4, 2017. In March 2018, the patient got an operation including pancreatectomy and diagnosed with no evidence of disease state in September, 2018. In conclusion, it showed the overall survival of 29 months from June, 2016 to November, 2018. Serious adverse events were not identified. Conclusions: This study suggested that combined treatment with modified Bangam-tang and Gunchil-dan may show better outcome in patient with metastatic pancreatic cancer than gemcitabine alone.

• Journal of Life Science
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• v.24 no.10
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• pp.1137-1143
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• 2014

Doxorubicin is a general chemotherapy drug widely used for a number of cancers. However, the correlation between endogenous nitric oxide ($NO^{\bullet}$) levels and chemoresistance to doxorubicin remains unclear. In this study, we investigated the effect of endogenous $NO^{\bullet}$ on the anticancer activity of doxorubicin in human colon cancer cell lines HCT116 and HT29 with different p53 status. The cells were treated with either doxorubicin alone or in combination with the $NO^{\bullet}$ synthase (NOS) inhibitor $N^G$-monomethyl-L-arginine (NMA). Doxorubicin differentially inhibited the growth of both the HCT116 (p53-WT) and HT29 (p53-MUT) cells, which was mitigated by cotreatment with NMA. Further studies revealed that inhibition of endogenous $NO^{\bullet}$ mitigated doxorubicin-induced apoptosis in the HCT116 and HT29 cells, as evidenced by apoptotic DNA fragmentation and the sub-G1 peak of apoptotic markers. Apoptosis was delayed in the HT29 cells, and its magnitude was greatly reduced, underscoring the importance of the modulation of p53 in the response. RT-PCR analysis revealed that doxorubicin down-regulated levels of inhibitors of the apoptosis family (cellular IAP-1 and-2). Collectively, these data show that induction of apoptosis by doxorubicin in human colon cancer cells is possibly related to modulation of endogenous $NO^{\bullet}$, the expression of the IAP family of genes, and the status of p53. The underlying mechanisms may represent potential targets for adjuvant strategies to improve the efficacy of chemotherapy for colon cancer.

• Journal of Korean Neurosurgical Society
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• v.30 no.5
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• pp.575-580
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• 2001

Purpose : In general, pineal region tumors are managed by using microsurgical approach or stereoctactic biopsy. However, in selected cases endoscopic approach to pineal lesions might prove to be as effective as microsurgery and less invasive. We report an alternative surgical strategy for managing certain patients with pineal neoplasms that allows treatment of the symptomatic hydrocephalus as well as tumor biopsy under direct vision in the same sitting. Materials and Methods : Twenty-two patients with pineal region tumors with associated hydrocephalus were treated in one session by endoscopic third ventriculostomy and endoscopic tumor biopsy at our institution from October 1996 to January 2000. All patients were retrospectively evaluated. Results : There was no operative mortality. There was one cause of significant bleeding during biopsy, but was controlled endoscopically, and the patient recovered completely without neurologic deficit resulting from intra-operative bleeding. The symptoms related to increased intracranial pressure(ICP) have resolved in all patients, and the need for a shunt is completely eliminated. Histological diagnosis was achieved in 21 of the 22 patients by this procedure. A biopsy was not obtained in one patient. Although this pineal region tumor was seen endoscopically, this could not be biopsied because of technical difficulties in working around an enlarged massa intermedia. The lesions included fourteen germinomas, three mixed germ cell tumors, and one each of the followings: pineocytoma, pineoblastoma, pineocytoma/pineoblastoma(intermediate type), meningioma, and low grade glioma. Five of the 22 patients subsequently underwent formal microsurgical tumor removal. Additional chemotherapy or radiotherapy could then be initiated according to the histological diagnosis. Conclusion : We consider that endoscopy affords a minimally invasive way of reaching three objectives by one-step surgery in the management of pineal region tumors with associated hydrocephalus : 1) cerebrospinal fluid(CSF) sample for analysis of tumour markers and cytology, 2) treatment of hydrocephalus by third ventriculostomy, and 3) several biopsy specimens can be obtained identifying tumors which will require further open surgery or adjuvant radiation and/or chemotherapy. However, complications and morbidities should be emphasized so as to be avoided with further technical experience.

• Journal of Life Science
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• v.30 no.8
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• pp.661-671
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• 2020

The resistance of cancer cells to anti-cancer drugs is the leading cause of chemotherapy failure. The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been gradually extended to cancer treatment through combination with anti-cancer drugs. In the current study, we investigated whether NSAIDs including celecoxib (CCB), 2,5-dimethyl celecoxib (DMC), and ibuprofen (IBU) could enhance the cytotoxic effects of imatinib and TNF-related apoptosis inducing ligand (TRAIL) on human cancer cells. We found that the NSAIDs potentiated TRAIL and imatinib cytotoxicity against human hepatocellular carcinoma (HCC) cell lines SNU-354, SNU-423, SNU-449, and SNU-475/TR and against leukemic K562 cells with high level of CD44 (CD44^highK562), respectively. More specifically, CCB induced endoplasmic reticulum stress via up-regulation of ATF4/CHOP which is associated with the induction of autophagy against HCC and CD44^high K562 cells. NSAID-induced autophagic activity accelerated TRAIL cytotoxicity of HCC cells through up- and down-regulation of DR5 and c-FLIP, respectively. The NSAIDs also potentiated imatinib-induced cytotoxicity and apoptosis through down-regulation of markers in CD44^highK562 cells that express a stemness phenotype. Our results suggest that the ability of NSAIDs to induce autophagy could enhance the cytotoxicity of TRAIL and imatinib, leading to a reverse resistance to these drugs in the cancer cells. In conclusion, NSAIDs in combination with low-dose TRAIL or imatinib may constitute a novel clinical strategy that maximizes therapeutic efficacy of each drug and effectively reduces the toxic side effects.