• IMMUNE NETWORK
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• v.12 no.6
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• pp.269-276
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• 2012

The anti-tumor effect of monocyte-derived DC (MoDC) vaccine was studied in lung cancer model with feasible but weak Ag-specific immune response and incomplete blocking of tumor growth. To overcome this limitation, the hematopoietic stem cell-derived DC (SDC) was cultured and the anti-tumor effect of MoDC & SDC was compared in mouse lung cancer minimal residual model (MRD). Therapeutic DCs were cultured from either $CD34^+$ hematopoietic stem cells with GM-CSF, SCF and IL-4 for 14 days (SDC) or monocytes with GM-CSF and IL-4 for 7 days (MoDC). DCs were injected twice by one week interval into the peritoneum of mice that are inoculated with Lewis Lung Carcinoma cells (LLC) one day before the DC injection. Anti-tumor responses and the immune modulation were observed 3 weeks after the final DC injection. CD11c expression, IL-12 and TGF-${\beta}$ secretion were higher in SDC but CCR7 expression, IFN-${\gamma}$ and IL-10 secretion were higher in MoDC. The proportion of $CD11c^+CD8a^+$ cells was similar in both DC cultures. Although both DC reduced the tumor burden, histological anti-tumor effect and the frequencies of IFN-${\gamma}$ secreting $CD8^+$ T cells were higher in SDC treated group than in MoDC. Conclusively, although both MoDC and SDC can induce the anti-tumor immunity, SDC may be better module as anti-tumor vaccine than MoDC in mouse lung cancer.

• Animal cells and systems
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• v.6 no.3
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• pp.263-269
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• 2002

The p53 tumor suppressor gene is among the most frequently mutated and studied genes in human cancer, but the mechanisms by which it sur presses tumor formation remain unclear. DNA damage regulates both the protein levels of p53 and its affinity for specific DNA sequences. Stabilization of p53 in response to DNA damage is caused by its dissociation from Mdm2, a downstream target gene of p53 and a protein that targets p53 for degradation in the proteosome. Recent studies have suggested that phosphorylation of human p53 at Ser20 is important for stabilizing p53 in response to DNA damage through disruption of the interaction between Mdm2 and p53. We generated mice with an allele encoding changes at Ser20, known to be essential for p53 accumulation following DNA damage, to enable analyses of p53 stabilization in vivo. Our data showed that the mutant p53 was clearly defective for full stabilization of p53 in response to DNA damage. We concluded that Ser20 phosphorylation is critical for modulating the negative regulation of p53 by Mdm2, probably through phosphorylation-dependent inhibition of p53-Mdm2 interaction in the physiological context.

• Journal of Korean Neurosurgical Society
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• v.57 no.4
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• pp.307-310
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• 2015

We report a case of a paradoxical response of a tuberculoma in the brain mimicking a brain tumor. A 76-year-old woman presented with a 2 week history of headache, dysarthia, and orthopnea. Brain magnetic resonance images (MRI) revealed two rim-enhancing lesions on the pons and occipital lobe, and chest computed tomography showed randomly distributed miliary nodules. The tentative diagnosis was tuberculosis (TB) of the brain and lung. She complained of right hemiparesis and worsening general weakness after taking the anti-TB medication. On the monthly follow-up images, the enhanced lesions were enlarged with increased perfusion and choline/creatinine ratio, suggesting a high grade glioma. A surgical resection was completed to diagnose the occipital lesion, and the tuberculoma was pathologically confirmed by a positive TB-polymerase chain reaction. The anti-TB medication was continued for 13 months. A follow-up MRI showed decreased size of the brain lesions associated with perilesional edema, and the clinical symptoms had improved. Brain tuberculoma could be aggravated mimicking brain malignancy during administration of anti-TB medication. This paradoxical response can be effectively managed by continuing the anti-TB drugs.

• Radiation Oncology Journal
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• v.33 no.2
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• pp.117-125
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• 2015

Purpose: To investigate the relationship between early treatment response to definitive chemoradiotherapy (CRT) and survival outcome in patients with limited stage small cell lung cancer (LS-SCLC). Materials and Methods: We retrospectively reviewed 47 patients with LS-SCLC who received definitive CRT between January 2009 and December 2012. Patients were treated with systemic chemotherapy regimen of etoposide/carboplatin (n = 15) or etoposide/cisplatin (n = 32) and concurrent thoracic radiotherapy at a median dose of 54 Gy (range, 46 to 64 Gy). Early treatment volume reduction rate (ETVRR) was defined as the percentage change in gross tumor volume between diagnostic computed tomography (CT) and simulation CT for adaptive RT planning and was used as a parameter for early treatment response. The median dose at adaptive RT planning was 36 Gy (range, 30 to 43 Gy), and adaptive CT was performed in 30 patients (63.8%). Results: With a median follow-up of 27.7 months (range, 5.9 to 75.8 months), the 2-year locoregional progression-free survival (LRPFS) and overall survival (OS) rates were 74.2% and 56.5%, respectively. The mean diagnostic and adaptive gross tumor volumes were 117.9 mL (range, 5.9 to 447 mL) and 36.8 mL (range, 0.3 to 230.6 mL), respectively. The median ETVRR was 71.4% (range, 30 to 97.6%) and the ETVRR >45% group showed significantly better OS (p < 0.0001) and LRPFS (p = 0.009) than the other group. Conclusion: ETVRR as a parameter for early treatment response may be a useful prognostic factor to predict treatment outcome in LS-SCLC patients treated with CRT.

• The Korean journal of helicobacter and upper gastrointestinal research
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• v.18 no.4
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• pp.264-270
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• 2018

Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor derived from Cajal cells originating from the myotonic plexus. The expression of tyrosine kinase (KIT) membrane receptors that are active on KIT is inhibited by the KIT inhibitor imatinib mesylate. GISTs are resistant to conventional chemotherapy, and radiation therapy is not significantly beneficial for GISTs. With the development of imatinib mesylate, approximately 81.6% of patients with advanced and metastatic GIST exhibit an effect above the stabilization response, thereby increasing the survival time. However, imatinib mesylate alone is unlikely to cure metastatic GISTs. Even with a partial or stable response, imatinib mesylate may be used for a longer time period. However, resection of grossly visible lesions should be considered for patients with a stable response during surgical treatment. In this study, we present a case of GIST with liver metastasis after imatinib mesylate treatment, which was followed up without recurrence after partial resection.

• Tuberculosis and Respiratory Diseases
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• v.82 no.1
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• pp.62-70
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• 2019

Background: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancers have emerged as key predictive biomarkers in EGFR tyrosine kinase inhibitor (TKI) treatment. However, a few patients with wild-type EGFR also respond to EGFR TKIs. This study investigated the factors predicting successful EGFR TKI treatment in lung adenocarcinoma patients with wild-type EGFR. Methods: We examined 66 patients diagnosed with lung adenocarcinoma carrying wide-type EGFR who were treated with EGFR TKIs. The EGFR gene copy number was assessed by silver in situ hybridization (SISH). We evaluated the clinical factors and EGFR gene copy numbers that are associated with a favorable clinical response to EGFR TKIs. Results: The objective response rate was 12.1%, while the disease control rate was 40.9%. EGFR SISH analysis was feasible in 23 cases. Twelve patients tested EGFR SISH-positive, and 11 were EGFR SISH-negative, with no significant difference in tumor response and survival between EGFR SISH-positive and -negative patients. The overall median progression-free survival (PFS) and overall survival (OS) of 66 patients were 2.1 months and 9.7 months, respectively. Female sex and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 were independent predictors of PFS. ECOG PS 0-1 and a low tumor burden of extrathoracic metastasis were independent predictors of good OS. Conclusion: Factors such as good PS, female sex, and low tumor burden may predict favorable outcomes following EGFR TKI therapy in patients with EGFR wild-type lung adenocarcinoma. However, EGFR gene copy number was not predictive of survival.

• Radiation Oncology Journal
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• v.27 no.2
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• pp.55-63
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• 2009

Purpose: This study was performed to objectively evaluate the rate of tumor response to hypofractionated radiotherapy for advanced squamous cell carcinomas of the head and neck. Materials and Methods: Thirty-one patients with advanced squamous cell carcinoma of the head and neck, who were treated by hypofractionated radiotherapy with 3 Gy per fraction for palliative purpose between 1998 and 2008, were reviewed retrospectively. Every tumor-volume was measured and evaluated from CT (computed tomography) images obtained before and 2~3 months after radiotherapy. The radiation toxicity was assessed during and after radiotherapy. A statistical analysis was performed to investigate overall survival, progressionfree survival, and the prognostic factors for survival and response. Results: The median age of the study patients was 70 years. In addition, 85% of the patients were in stage 4 cancer and 66.7% had an ECOG performance status of 1~2. The mean tumor-volume was 128.4 cc. Radiotherapy was administered with a total dose of 24~45 Gy (median: 36 Gy) over 10~25 days. Twenty-nine patients were treated with 30 Gy or more. The observed complete response rate was 12.9% and the partial response rate was 61.3%. Median survival time was 8.9 months and the 1-year progression-free survival rate was 12.9%. The treatment response rate was confirmed as a prognostic factor in the rate of survival. The primary site, stage, tumor-volume, radiotherapy field and overall radiation-dose showed a significant relationship with survival and treatment response. No grade 4 toxicity was observed during and after radiotherapy. Conclusion: There was an objective tumor-regression in about 74% of patients treated by hypofractionated radiotherapy. Further evaluation is needed to select the appropriate fraction-size and patient who may require the additional radiotherapy.

• Journal of Korean Neurosurgical Society
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• v.61 no.3
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• pp.292-301
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• 2018

Medulloblastoma is the most common malignant brain tumor of childhood and remains a major cause of cancer related mortality in children. Significant scientific advancements have transformed the understanding of medulloblastoma, leading to the recognition of four distinct clinical and molecular subgroups, namely wingless (WNT), sonic hedgehog, group 3, and group 4. Subgroup classification combined with the recognition of subgroup specific molecular alterations has also led to major changes in risk stratification of medulloblastoma patients and these changes have begun to alter clinical trial design, in which the newly recognized subgroups are being incorporated as individualized treatment arms. Despite these recent advancements, identification of effective targeted therapies remains a challenge for several reasons. First, significant molecular heterogeneity exists within the four subgroups, meaning this classification system alone may not be sufficient to predict response to a particular therapy. Second, the majority of novel agents are currently tested at the time of recurrence, after which significant selective pressures have been exerted by radiation and chemotherapy. Recent studies demonstrate selection of tumor sub-clones that exhibit genetic divergence from the primary tumor, exist within metastatic and recurrent tumor populations. Therefore, tumor resampling at the time of recurrence may become necessary to accurately select patients for personalized therapy.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.5
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• pp.271-274
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• 2006

We report the case of a 64-year-old man with superior vena cava (SVC) syndrome due to tumor thrombus from recurrent hepatocellular carcinoma (HCC). He presented with new onset of facial swelling for 10 days. HCC was detected ten years ago. He has undergone repeated transcatheter arterial embolization (TAE) and chemotherapy. Chest computed tomography (CT) demonstrated tumor thrombus in the SVC extending to right atrium. He underwent whole body F-18 fluorodeoxyglucose(FDG) positron emission tomography/computed tomography (PET/CT) scanning for assessing the effect of TAE in HCC. F-18 FDG PET/CT showed increased uptake in the residual liver mass indicating viable tumor. There was another intense F-18 FDG accumulation in SUV extending to right atrium to suggest tumor thrombus. This case illustrates that F-18 FDG PET/CT is useful to identification of distant metastases as well as assessment of response to therapy in long-term survival HCC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3659-3665
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• 2014

To assess inhibition mechanisms of a Phellinus igniarius (PI) extract on cancer, C57BL/6 mice were orally treated with PI extractive after or before implanting H22 (hepatocellular carcinoma ) or B16 (melanoma) cells. Mice were orally gavaged with different doses of PI for 36 days 24h after introduction of H22 or B16 cells. Mice in another group were orally treated as above daily for 42 days and implanted with H22 cells on day 7. Then the T lymphocyte, antibody, cytokine, LAK, NK cell activity in spleen, tumor cell apoptosis status and tumor inhibition in related organs, as well as the expression of iNOS and PCNA in tumor tissue were examined. The PI extract could improve animal immunity as well as inhibit cancer cell growth and metastasis with a dose-response relationship. Notably, PI's regulation with the two kinds of tumor appeared to occur in different ways, since the antibody profile and tumor metastasis demonstrated variation between animals implanted with hepatocellular carcinoma and melanoma cells.