• 대한핵의학회지
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• 제24권1호
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• pp.29-36
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• 1990

Most of the diagnostic methods currently used for the detection of neoplastic masses provide indirect evidence. To obtain greater specificity in the interpretation of neoplasias by in vivo methods, the immunological approach appears to be most promising. Two problems that interfered with progress in this field were the lack of tumor specific antigen and the lack of well-defined and reproducible antibodies. To improve the sensitivity and specificity of radioimmunoscintigraphy as a technique for tumor localization, the use of monoclonal antibodies, fragments of antibodies and single photon emission computerized tomography (SPECT) are reasonable. The obvious advantages of monoclonal antibodies are their homogeneity, their specificity for the immunizing antigen and the reaction with a single determinant-thus no large immunecomplexes with antigen are formed. Monoclonal antibody technique has recently provided an opportunity to reevaluate the role of nuclear medicine for the diagnosis of malignant diseases by using the immunological approach. Out first results by means of radioimmunoscintigraphy of CEA and CA 19-9 producing tumors using a cocktail of fragments F $(ab')_2$, of mocolonal antibodies to CA 19-9 and CEA labeled with $^{131}I$ (IMACIS-1) are reported. The aims of this investigation was to evaluate the role of immunoscintigraphy in patients with colorectal and other cancers for diagnosis of local recurrences and metastasis. This report contains results of the first 8 colorectal and pancreas cancer patients with the elevation of the level of serum CEA and/or CA 19-9. IMACIS-1 was injected intravenously during 30 minutes in 100 ml saline solution after skin test. Planar scintigrams were recorded 3, 5 and 7 days after the injection of the IMACIS-1. Anterior, lateral and posterior views of the liver as well as anterior and posterior views of the pelvis were obtained in each patients as an $^{131}I-antibody$ image. We were able to localize exactly the malignant process with the double-nuclide double-compound $^{99m}Tc\;^{131}I$ (Tc+l) scintigrams. In Tc & I double-nuclide scintigraphy, computer subtraction display provided more clear localization of the tumor. We compared the results of radioimmunoscintigraphy with CT, ultrasonograms, conventional scintigrams. The results were as follows: 1) The sensitivity and specificity of radioimmunoscintigraphy using the fragments $F(ab')_2$ of the cocktails of CEA and CA 19-9 monoclonal antibodies were 80% and 100% respectively. 2) Tumor detection rate was not proportionated to the level of serum tumor markets. 3) Second tracer technique was essential for tumor localization as an anatomic landmark using double-nuclide scintigraphy. 4) A slow infusion of the antibodies was necessary to prevent the formation of large immune complexes. 5) Tumor/non-tumor radioactivity was most elevated at 7 days delayed imaging. 6) Using planar scintigraphic technique of $^{131}I$ labeled monoclonal antibodies are possible for imaging most of the tumors.

• IMMUNE NETWORK
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• 제5권2호
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• pp.110-116
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• 2005

Background: As an attempt to develop a strategy to improve the protective immune response to GM-CSF-secreting CT26 (GM-CSF/CT26) tumor vaccine, we have investigated whether the apoptogenic treatment of GM-CSF/CT26 prior to vaccination enhances the induction of anti-tumor immune response in mouse model. Methods: A carcinogeninduced mouse colorectal tumor, CT26 was transfected with GM-CSF gene using a retroviral vector to generate GM-CSF-secreting CT26 (CT26/GM-CSF). The CT26/GM-CSF was treated with ${\gamma}$-irradiation or mitomycin C to induce apoptosis and vaccinated into BALB/c mice. After 7 days, the mice were injected with a lethal dose of challenge live CT26 cells to examine the protective effect of tumor vaccination in vivo. Results: Although both apoptotic and necrotic CT26/GM-CSF vaccines were able to enhance anti-tumor immune response, apoptotic CT26/GM-CSF induced by pretreatment with ${\gamma}$-irradiation (50,000 rads) was the most potent in generating the anti-tumor immunity, and thus 100% of mice vaccinated with the apoptotic cells remained tumor free for more than 60 days after tumor challenge. Conclusion: Apoptogenic pretreatment of GM-CSF-secreting CT26 tumor vaccine by ${\gamma}$-irradiation (50,000 rads) resulted in a significant enhancement in inducing the protective anti-tumor immunity. A rapid induction of apoptosis of CT26/GM-CSF tumor vaccine at the vaccine site might be critical for the enhancement in anti-tumor immune response to tumor vaccine.

• Journal of Nutrition and Health
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• 제27권6호
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• pp.552-562
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• 1994

The study was designed to observe the effect of different dietary fats on the incidence of colorectal tumor and in vivo cell proliferation in colon carcinogenesis. Male Sprague Dawley rats were intrarectally infused with chemical carcinogen(methylnitrosourea, MNU) and fed 16%(w/w) fat diet containing one of dietary fats(beef tallow, corn oil, perilla oil) for 30 weeks. To measure in vivo cell proliferation, the incorporation of 5-bromo-2-deoxyuridine(BrdU) into DNA was localized using the monoclonal anti-BrdU antibody. Large number of tumors were found in the distal colon and tumor incidence was increased in the order of perilla oil(57.7%)$\alpha$-linolenic acid rich in perilla oil could have a protective effect against colon cancer compared to saturated fatty acid or n-6 linoleic acid.

• Journal of Pharmaceutical Investigation
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• 제36권6호
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• pp.385-392
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• 2006

Paclitaxel is an important chemotherapeutic agent for the treatment of human solid tumors. Multicellular resistance(MCR) is considered to be a major mechanism of resistance of human solid tumors to chemotherapeutic agent such as paclitaxel, which includes barriers to drug penetration through tumor tissues. Multicellular layers(MCL) cultures resemble in vivo tumor condition in terms of MCR and has been used successfully to produce clinically relevant data. In the present study, we evaluated the penetration characteristics and post-penetration anti-proliferative activity of paclitaxel using MCL of human colorectal cancer cells(DLD-1 and HT-29) grown in Transwell inserts. The penetration of $[^{14}C]-paclitaxel$ was slower than that of mannitol which penetrates via paracellular pathway in DLD-1 MCL. The penetration of $[^{14}C]-paclitaxel$ was faster in HT-29 MCL compared to DLD-1 MCL, i.e., at 10 ${\mu}M$ 100% and 40% penetration were observed after 48 hr incubation for HT-29 and DLD-1 cells, respectively. When calculated using anti-proliferative activity in the conditioned media of bottom chamber, the penetration after 24 hr was very limited(less than 50%) and concentration-dependent at the concentrations tested in both MCL's. These results suggest that limited and differential penetration of paclitaxel in tumor tissues may contribute to lower and differential efficacy against human solid tumors.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4447-4453
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• 2013

Purpose: To investigate the risk factors for anastomotic leakage (AL) after anterior resection for rectal cancer with a double stapling technique. Patients and Methods: Between January 2004 and December 2011, 753 consecutive patients in Jiangsu Cancer Hospital and Research Institute diagnosed with rectal cancer and undergoing anterior resection with a double stapling technique were recruited. All patients experienced a total mesorectal excision (TME) operation. Additionally, decrease of postoperative tumor supplied group of factors (TSGF), which have not been reported before, was proposed as a new indicator for AL. Univariate and multivariate analysis were performed to determine risk factors for AL. Results: AL was detected in 57 (7.6%) of 753 patients with rectal cancer. The diagnosis of anastomotic leakage was confirmed between the 6th and 12th postoperative day (POD; mean 8th POD). After univariate analysis and multivariate analysis, age (p<0.001), gender (p=0.002), level of anastomosis (p<0.001), preoperative body mass index (BMI) (p=0.001) and reduction of TSGF in 5th POD was less than 10 ${\mu}/ml$ (p<0.001) were selected as 5 independent risk factors for AL. It was also indicated that a temporary defunctioning transverse ileostomy (p=0.04) would decrease the occurrence of AL. Conclusion: AL after anterior resection for rectal carcinoma is related to elderly status, low level site of the tumor (below the peritoneal reflection), being male, preoperative BMI and the decrease of TSGF in $5^{th}$ POD is less than 10 ${\mu}/ml$. Preventive ileostomy is advisable after TME for low rectal tumors to prevent AL.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.5111-5113
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• 2015

Background: To investigate the diagnostic and treatment methods for Chinese patients with gastrointestinal stromal tumor (GIST). Materials and Methods: From January 2004 to June 2014, patients diagnosed with primary GIST and treated by a single medical team in the Department of Digestive Disease of XuYi Hospital of Traditional Chinese Medicine were retrospectively recruited. Re-examination and follow-up was conducted regularly and abdominal enhanced CT, blood biochemistry and responses to surgery or imatinib were recorded. Results: A total of 15 patients were enrolled, including 9 male and 6 female patients, with an average age of 54 years (ranging from 32-81 years). The primary symptoms were abdominal uncomfortable in 5 patients, abdominal pain in 6 patients as well as nausea and vomiting in 4 patients. One patient was diagnosed with bowl obstruction at the first visit. All patients were treated with surgery, and tumor site was confirmed 1 esophagus, 6 stomach, 4 small bowel, and 4 colorectal and all patients were pathologically diagnosed with GIST. Immunochemical test positive for CD 117 was found 12 patients, and positive for CD 34 in7 patients. The median follow-up time was 24 months (range of 3-63). Three metastasis were confirmed 1.5, 2 and 2.6 years postoperatively. Three patients were treatment by imatinib postoperatively. Conclusions: Surgery remains the main treatment method for Chinese patients with GIST and imatinib could be feasible and safe for treating Chinese patients with GIST.

• Nutrition Research and Practice
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• 제16권2호
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• pp.161-172
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• 2022

BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide and has a high recurrence rate, which is associated with cancer stem cells (CSCs). β-carotene (BC) possesses antioxidant activity and several anticancer mechanisms. However, no investigation has examined its effect on colon cancer stemness. MATERIALS/METHODS: CD133⁺CD44⁺ HCT116 and CD133⁺CD44⁺ HT-29 cells were isolated and analyzed their self-renewal capacity by clonogenic and sphere formation assays. Expressions of several CSCs markers and Wnt/β-catenin signaling were examined. In addition, CD133⁺CD44⁺ HCT116 cells were subcutaneously injected in xenograft mice and analyzed the effect of BC on tumor formation, tumor volume, and CSCs markers in tumors. RESULTS: BC inhibited self-renewal capacity and CSC markers, including CD44, CD133, ALDH1A1, NOTCH1, Sox2, and β-catenin in vitro. The effects of BC on CSC markers were confirmed in primary cells isolated from human CRC tumors. BC supplementation decreased the number and size of tumors and delayed the tumor-onset time in xenograft mice injected with CD133⁺CD44⁺ HCT116 cells. The inhibitory effect of BC on CSC markers and the Wnt/β-catenin signaling pathway in tumors was confirmed in vivo as well. CONCLUSIONS: These results suggest that BC may be a potential therapeutic agent for colon cancer by targeting colon CSCs.

• IMMUNE NETWORK
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• 제12권2호
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• pp.66-69
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• 2012

The immunological death induction by EY-6 on the human tumor cell lines was screened. Human colon carcinoma (HCT15, HCT116), gastric carcinoma (MKN74, SNU668), and myeloma (KMS20, KMS26, KMS34) cells were died by EY-6 treatment with dose-dependent manner. CRT expression, a typical marker for the immunological death, was increased on the EY-6-treated colorectal and gastric cancer cells. Interestingly, the effects on the myeloma cell lines were complicated showing cell line dependent differential modulation. Cytokine secretion from the EY-6 treated tumor cells were dose and cell-dependent. IFN-${\gamma}$ and IL-12 secretion was increased in the treated cells (200% to over 1000% of non-treated control), except HCT116, SNU668 and KMS26 cells which their secretion was declined by EY-6. Data suggest the potential of EY-6 as a new type of immuno-chemotherapeutics inducing tumor-specific cell death. Further studies are planned to confirm the efficacy of EY-6 including in vivo study.

• 대한핵의학회지
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• 제19권1호
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• pp.119-126
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• 1985

To evaluate the performance characteristics of CA 19-9 radioimmunoassay and the clinical significance of serum CA 19-9 assay in patients with malignancy, serum CA 19-9 levels were measured by radioimmunoassay using monoclonal antibody in 135 normal controls, 81 patients with various untreated malignancy, 9 patients of postoperative colon cancer without recurrence and 20 patients with benign gastrointestinal diseases, who visited Seoul National University Hospital from June, 1984 to March, 1985. The results were as follows; 1) The CA 19-9 radioimmunoassay was simple to perform and can be completed in one work day. And the between-assay reproducibility and the assay recovery were both excellent. 2) The mean serum CA 19-9 level in 135 normal controls was $8.4{\pm}4.2U/mL$. Normal upper limit of serum CA 19-9 was defined as 21.0 U/mL. 4 out of 135(3.0%) normal controls showed elevated CA 19-9 levels above the normal upper limit. 3) One out of 20(5.0%) patients with benign gastrointestinal diseases showed elevated serum CA 19-9 level above the normal upper limit. 4) In 81 patients with various' untreated malignancy, 41 patients(50.6%) showed elevated serum CA 19-9 levels. 66.7% of 18 patients with colorectal cancer, 100% of 2 patients with pancreatic cancer, 100% of 3 patients with common bile duct cancer, 47.1% of 17 patients with stomach cancer, 28.6% of 28 patients with hepatoma and 60.0% of 5 other gastrointestinal tract cancers showed elevated serum CA 19-9 levels. 5) The sensitivities of serum CA 19-9 related to resectability in colorectal and stomach cancer were 33.3% in resectable colorectal cancer, 83.3% in unresectable colorectal cancer, 41.7% in resectable stomach cancer, 60.0% in unresectable stomach cancer respectively. 6) The sensitivity of serum CA 19-9 in 9 patients of postoperative colorectal cancer without recurrence were 33.3% and significantly decreased compared with that of untreated colorectal cancer, 66.7% (p<0.05). 7) In patients with colorectal cancer, simultaneous measurement of serum CA 19-9 and serum CEA levels increased sensitivities. From above results, we concluded that serum CA 19-9 radioimmunoassay is simple to perform and reproducible, and is a useful indicator reflecting tumor extent and responses to the treatment in patients with malignancy.

• Biomolecules & Therapeutics
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• 제23권2호
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• pp.128-133
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• 2015

Although coffee is known to have antioxidant, anti-inflammatory, and antitumor properties, there have been few reports about the effect and mechanism of coffee compounds in colorectal cancer. Heat shock proteins (HSPs) are molecular chaperones that prevent cell death. Their expression is significantly elevated in many tumors and is accompanied by increased cell proliferation, metastasis and poor response to chemotherapy. In this study, we investigated the cytotoxicity of four bioactive compounds in coffee, namely, caffeine, caffeic acid, chlorogenic acid, and kahweol, in HT-29 human colon adenocarcinoma cells. Only kahweol showed significant cytotoxicity. Specifically, kahweol increased the expression of caspase-3, a pro-apoptotic factor, and decreased the expression of anti-apoptotic factors, such as Bcl-2 and phosphorylated Akt. In addition, kahweol significantly attenuated the expression of HSP70. Inhibition of HSP70 activity with triptolide increased kahweol-induced cytotoxicity. In contrast, overexpression of HSP70 significantly reduced kahweol-induced cell death. Taken together, these results demonstrate that kahweol inhibits colorectal tumor cell growth by promoting apoptosis and suppressing HSP70 expression.