• Radiation Oncology Journal
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• v.8 no.2
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• pp.207-212
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• 1990

To determine the correlation between the response to induction chemotherapy and subsequent radiotherapy we analyzed the clinical records of 60 patients with locally advanced carcinoma of the head and neck retrospectively who had completed a full course ($2\~3$ cycle) of induction chemotherapy and curative radiotherapy in Korea Cancer Center Hospital between 1986 and 1989. Chemotherapy was administeredd with CDDP+Bleomycin (BP) in 20, CDDP+5-FU (FP) in 37, and hybrid of BP and FP in three patients. Radiotherapy was giver conventionally with a dose of 65 to 75 Gy or more over seven to eight weeks according to the size of lesion. Response rates following induction chemotherapy were $80\%$ for the tumors and $879\%$ for the nodes whereas complete reponse rates were $12\%\;and\;13\%$, respectively. Six months after radiotherapy $67\%$ of the tumors and $77\%$ of the nodes achieved a complete response. Among the 48 tumor responders and the 31 nodal responders to chemotherapy,39 ($81\%$) and 28 ($90\%$), respectively, achieved complete response after radiotherapy. Thus, whether or not the tumor and node respond to induction chemotherapy was predictive of the response to subsequent radiotherapy (p<0.0005 in tumor, p<0.0001 in node). By reanalyzing according to disease subsets (i.e. primary site, T-stage, N-stage) this relationship was not observed at T1-T2 disease (p>0.3). Therefore the tumor or node's response to induction chemotherapy is a predictor for subsequent radiotherapy except in T1-T2 tumors, and complete response to radiotherapy can be expected despite the failure of induction chemotherapy in $T_1-T_2$ tumors.

• Biomolecules & Therapeutics
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• v.18 no.2
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• pp.145-151
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• 2010

Oxygen supply into inside solid tumor is often diminished, which is called hypoxia. Many gene transcriptions were activated by hypoxia-inducible factor (HIF)-$1{\alpha}$. Here, we investigated the effect of hypoxia on paclitaxel-resistance induction in HeLa cervical tumor cells. When HeLa cells were incubated under hypoxia condition, HIF-$1{\alpha}$ level was increased. In contrast, paclitaxel-mediated tumor cell death was reduced by the incubation under hypoxia condition. Paclitaxel-mediated tumor cell death was also inhibited by treatment with DMOG, chemical HIF-$1{\alpha}$ stabilizer, in a dose-dependent manner. A significant increase in intracellular ROS level was detected by the incubation under hypoxia condition. A basal level of cell density was increased in response to 10 nM $H_2O_2$. HIF-$1{\alpha}$ level was increased by treatment with various concentration of $H_2O_2$. The increased level of HIF-$1{\alpha}$ by hypoxia was reduced by the treatment with N-acetylcysteine (NAC), a well-known ROS scavenger. Paclitaxel-mediated tumor cell death was increased by treatment with NAC. Taken together, these findings demonstrate that hypoxia could play a role in paclitaxel-resistance induction through ROS-mediated HIF-$1{\alpha}$ stabilization. These results suggest that hypoxia-induced ROS could, in part, control tumor cell death through an increase in HIF-$1{\alpha}$ level.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.4039-4044
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• 2014

Background: The aim of this study was to investigate the anti-cancer effects and mechanisms of immunochemotherapy of 5-fluorouracil (5-FU) and interleukin-2 (IL-2) on non-small cell lung cancer (NSCLC) A549 cells. Materials and Methods: In order to detect whether 5-FU+IL-2 could effectively inhibit tumor growth in vivo, we established an A549-bearing nude mouse model. The cytotoxicity of natural killer (NK) cells was evaluated using a standard chromium release assay. To evaluate the relevance of NK cells in 5-FU+IL-2-mediated tumor inhibitory effects, we depleted NK cells in A549-bearing mice by injecting anti-asialo-GM-1 antibodies. Effects of 5-FU+IL-2 on the expression and promoter activity of NKG2D ligands (MICA/MICB) in A549 cells in vitro were also assessed. Results: In A549-bearing nude mice, combination therapy significantly inhibited tumor growth in comparison with monotherapy with 5-FU or IL-2 and enhanced the recognition and lysis of tumor cells by NK cells. Further study of mechanisms showed that NK cells played a vital role in the anticancer immune response of 5-FU+IL-2 immunochemotherapy. In addition, the combination therapy synergistically stimulated the expression and promoter activity of MICA/MICB. Conclusions: 5-FU and IL-2 immunochemotherapy significantly inhibited tumor growth and activated NK cytotoxicity in vivo, and these effects were partly impaired after depleting NK cells in tumor-bearing mice. Combination treatment of 5-FU and IL-2 upregulated the expression and the promoter activity of MICA/MICB in A549 cells, which enhanced the recognition of A549 cells by NK cells. All of the data indicated that immunochemotherapy of 5-FU and IL-2 may provide a new treatment option for patients with lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6721-6726
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• 2014

Background: The aim of this preliminary study was to address variations of responses observed with different starting tumor sizes of 10 and 15 mm, and the effects of different doses of tamoxifen (TAM) on experimental rat mammary tumors. Materials and Methods: Thirty-five inbred female Sprague Dawley rats aged 43 days were administered with three weekly doses of N-methyl-N-nitrosourea (NMU) intraperitoneally (ip) at 50 mg/kg body weight. Animals were randomized (beginning from 10 mm tumor size) into four TAM-treated (50, 100, 200 and $500{\mu}g/day$) groups of six animals each, and another group (n=6) treated with TAM $100{\mu}g/day$ at starting tumour size of 15 mm. The animals were treated by oral gavage daily for 8 weeks before sacrifice. Results: Serum urea and creatinine, and overall physical tumor burden were significantly modulated in animals treated with variable doses of TAM compared to the untreated controls (n=5). Final body weight and tumor number were significantly different in the 10 mm-treated animals compared to those treated at 15 mm. There were no significant differences in histopathological features among all the groups. Conclusions: Our findings suggest the importance of standardizing tumour size and drug doses before initiation of treatment, particularly in the direct comparison of basic end-tumour physical parameters.

• Journal of Chest Surgery
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• v.35 no.9
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• pp.692-696
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• 2002

Pulmonary artery sarcoma is a rare disease and hard to diagnose; therefore, suspicion is very important for the diagnosis and treatment. Surgical resection is almost always needed because of progressive right heart failure. Adjuvant chemotherapy and radiation therapy are still controversial. We report a case of a 42-year-old man who had a right pulmonary arterial tumor Curative resection was impossible because the tumor invaded the left pulmonary artery. Palliative endarterectomy was performed followed by radiation therapy. The patient refused the chemotherapy. Until the postoperative 6th month, the residual tumor was stable. However, 15 months later, follow-up chest computed tomography revealed a metastatic pulmonary nodule at left lower lobe and the increased residual tumor. The patient received chemotherapy with limited tumor response. The metastatic nodule and residual tumor did not increase but bone scan revealed a rib metastasis at postoperative 24 months. He will be receiving additional chemotherapy.

• Journal of Korean Neurosurgical Society
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• v.50 no.3
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• pp.179-184
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• 2011

Objective : The aim of this study is to evaluate the therapeutic effects of gamma knife radiosurgery (GKRS) in patients with multiple brain metastases and to investigate prognostic factors related to treatment outcome. Methods : We retrospectively reviewed clinico-radiological and dosimetric data of 36 patients with 4-14 brain metastases who underwent GKRS for 264 lesions between August 2008 and April 2011. The most common primary tumor site was the lung (n=22), followed by breast (n=7). At GKRS, the median Karnofsky performance scale score was 90 and the mean tumor volume was 1.2 cc (0.002-12.6). The mean prescription dose of 17.8 Gy was delivered to the mean 61.1% isodose line. Among 264 metastases, 175 lesions were assessed for treatment response by at least one imaging follow-up. Results : The overall median survival after GKRS was $9.1{\pm}1.7$ months. Among various factors, primary tumor control was a significant prognostic factor ($11.1{\pm}$1.3 months vs. $3.3{\pm}2.4$ months, p=0.031). The calculated local tumor control rate at 6 and 9 months after GKRS were 87.9% and 84.2%, respectively. Paddick's conformity index (>0.75) was significantly related to local tumor control. The actuarial peritumoral edema reduction rate was 22.4% at 6 months. Conclusion : According to our results, GKRS can provide beneficial effect for the patients with multiple (4 or more) brain metastases, when systemic cancer is controlled. And, careful dosimetry is essential for local tumor control. Therefore, GKRS can be considered as one of the treatment modalities for multiple brain metastase.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3109-3116
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• 2013

The majority of hepatocellular carcinoma (HCC) patients have a poor prognosis with current therapies, and new approaches are urgently needed. We have developed a novel therapeutic cancer vaccine platform based on tumor cell derived autophagosomes (DRibbles) for cancer immunotherapy. We here evaluated the effectiveness of DRibbles-pulsed dendritic cell (DC) immunization to induce anti-tumor immunity in BALB/c mouse HCC and humanized HCC mouse models generated by transplantation of human HCC cells (HepG2) into BALB/c-nu mice. DRibbles were enriched from H22 or BNL cells, BALB/c-derived HCC cell lines, by inducing autophagy and blocking protein degradation. DRibbles-pulsed DC immunization induced a specific T cell response against HCC and resulted in significant inhibition of tumor growth compared to mice treated with DCs alone. Antitumor efficacy of the DCs-DRibbles vaccine was also demonstrated in a humanized HCC mouse model. The results indicated that HCC/DRibbles-pulsed DCs immunotherapy might be useful for suppressing the growth of residual tumors after primary therapy of human HCC.

• Korean Journal of Radiology
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• v.22 no.11
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• pp.1797-1808
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• 2021

Objective: To determine whether volumetric CT texture analysis (CTTA) using fully automatic tumor segmentation can help predict recurrence-free survival (RFS) in patients with intrahepatic mass-forming cholangiocarcinomas (IMCCs) after surgical resection. Materials and Methods: This retrospective study analyzed the preoperative CT scans of 89 patients with IMCCs (64 male; 25 female; mean age, 62.1 years; range, 38-78 years) who underwent surgical resection between January 2005 and December 2016. Volumetric CTTA of IMCCs was performed in late arterial phase images using both fully automatic and semi-automatic liver tumor segmentation techniques. The time spent on segmentation and texture analysis was compared, and the first-order and second-order texture parameters and shape features were extracted. The reliability of CTTA parameters between the techniques was evaluated using intraclass correlation coefficients (ICCs). Intra- and interobserver reproducibility of volumetric CTTAs were also obtained using ICCs. Cox proportional hazard regression were used to predict RFS using CTTA parameters and clinicopathological parameters. Results: The time spent on fully automatic tumor segmentation and CTTA was significantly shorter than that for semi-automatic segmentation: mean ± standard deviation of 1 minutes 37 seconds ± 50 seconds vs. 10 minutes 48 seconds ± 13 minutes 44 seconds (p < 0.001). ICCs of the texture features between the two techniques ranged from 0.215 to 0.980. ICCs for the intraobserver and interobserver reproducibility using fully automatic segmentation were 0.601-0.997 and 0.177-0.984, respectively. Multivariable analysis identified lower first-order mean (hazard ratio [HR], 0.982; p = 0.010), larger pathologic tumor size (HR, 1.171; p < 0.001), and positive lymph node involvement (HR, 2.193; p = 0.014) as significant parameters for shorter RFS using fully automatic segmentation. Conclusion: Volumetric CTTA parameters obtained using fully automatic segmentation could be utilized as prognostic markers in patients with IMCC, with comparable reproducibility in significantly less time compared with semi-automatic segmentation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4037-4043
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• 2012

Despite progress in elucidating mechanisms associated with colorectal cancer and improvement of treatment methods, it remains a frequent cause of death worldwide. New and more effective therapies are therefore urgently needed. Recent studies have shown that immunogenicity of whole ovarian tumor cells and subsequent T cell response were potentiated by oxidation modification with hypochlorous acid (HOCl) in vitro and ex vivo. These results prompted us to investigate the protective antitumor response with an HOCl treated CT26 colorectal cancer cell vaccine in an in vivo mouse model. Administration of HOCl modified vaccine triggered robust antitumor immunity to autologous tumor cells in mice and prolonged survival period significantly. In addition, increased necrosis and apoptosis were found in tumor tissue from the oxidation group. Interestingly, ELISPOT assays showed that specific T cell responses were not elicited in response to the immunizing cellular antigen, in contrast to raising sera antibody titer and antibody binding activity shown by ELISA assay and flow cytometry. Further evaluation of the mechanisms underlying HOCl modified vaccine mediated humoral immunity highlighted the role of antibody-dependent cell-mediated cytotoxicity. These results combined with previous studies suggest that HOCl oxidation modified whole cell vaccine has wide applicability as a cancer vaccine because it can target both T cell- and B cell-specific responses. It may thus represent a promising approach for the immunotherapy of colorectal cancer.

• Journal of Life Science
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• v.17 no.1 s.81
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• pp.110-115
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• 2007

It has been previously described that transcription factor early growth response gene product 1 (EGR-1) functions as a tumor suppressor gene. This study was conducted to demonstrate that EGR-1 induction by phytochemical apigenin and its derivative isovitexin can mediate the growth suppression of the intestinal epithelial tumor cells. Apigenin and isovitexin induced EGR-1 gene expression both in the dose and time-dependent manners. Moreover the induction was relatively late around 9-12 hr after treatment of HCT-116 cells, while several anti-inflammatory agent such as NSAIDS and catechins elicit the ECR-1 gene expression at much earlier time about 1-3 hr after treatment. In terms of signal transduction, ERK1/2 was critical for apigenin-induced EGR-1 gene expression and its promoter activation. When EGR-1 gene expression was blocked with EGR-1 small interference RNA, the cytotoxicity of apigenin in the human epithelial cells was attenuated, suggesting the involvement of EGR-1 in the anti-tumoric activity of apigenin. To link the EGR-1 induction to EGR-1-regulated gene products in colon cancer, NSAID-Activated Gene 1 (NAG-1) was demonstrated to be elevated by apigenin and isovitexin at 24-48 hr after treatment. Taken together, apigenin-activated ERK1/2 mediated EGR-1 gene induction, which was associated with suppression of the cellular viability by apigenin compound.