TFAP2C (transcription factor-activating enhancer-binding protein 2C) expression has been positively correlated with poor prognosis in patients with certain types of cancer, but the mechanisms underlying TFAP2C-mediated tumorigenesis in non-small-cell lung cancer (NSCLC) are still unknown. We previously performed a microarray analysis to identify TFAP2C regulation genes, and TGFBR1 (transforming growth factor-β receptor type 1) was found to be upregulated by TFAP2C. We observed that TFAP2C or TGFBR1 overexpression led to oncogenic properties, such as cell viability, proliferation and cell cycle progression. TGFBR1 upregulation induced by TFAP2C also promoted cell motility and migration, leading to malignant development. We also found that PAK1 (p21 protein (Cdc42/Rac)-activated kinase 1) signaling was involved in TFAP2C/TGFBR1-induced tumorigenesis. These results were confirmed by an in vivo xenograft model and patient tissue samples. This study shows that TFAP2C promoted tumor progression by upregulation of TGFBR1 and consequent activation of PAK1 signaling.
Carcinogenesis* ; Cell Cycle ; Cell Movement ; Cell Survival ; Heterografts ; Humans ; Lung Neoplasms ; Lung* ; Microarray Analysis ; Phosphotransferases ; Prognosis ; Up-Regulation*

BACKGROUND: Burden of disease can be used to prioritize the healthcare budget allocation. We analyzed the research and development (R&D) budget of the Ministry of Health and Welfare (MOHW) in 2018 and compared the results with those of the 2015 Korean National Burden of Disease (KNBD) study. METHODS: The 2018 MOHW R&D Project integrated implementation plan was used to analyze the R&D budget of the MOHW. The budget was allocated according to the KNBD disease group and according to the budget lines. The allocated budget was compared with the economic burden and the disability adjusted life years (DALYs) in 2015. Also, for budget targets for risk factors, DALYs of attributable risk factors were compared with corresponding budgets. RESULTS: In 2018, the MOHW major R&D budget of USD 435.1 million accounted for 3% of the total government budget. Within the disease specific R&D budget, 35.9% was allocated to communicable disease groups, 64.1% to non-communicable diseases, and 0% to injury and violence. Among level 2 disease groups, neoplasm was ranked first. Among risk factors, climate change and behavioral risk were targeted for R&D. CONCLUSIONS It would be difficult to say that current R&D allocations focus to minimize the burden of disease. A mismatch was observed between the R&D budget and the burden of disease in terms of economic burden and DALYs. There was a similar finding for risk factors R&D. A novel approach for allocating government R&D funding that is based on the goal of minimizing the disease burden in the Korean population should be considered.

An interaction between ribosomal protein S3 (rpS3) and nuclear factor kappa B or macrophage migration inhibitory factor in non-small-cell lung cancer is responsible for radioresistance. However, the role of rpS3 in glioblastoma (GBM) has not been investigated to date. Here we found that in irradiated GBM cells, rpS3 translocated into the nucleus and was subsequently ubiquitinated by ring finger protein 138 (RNF138). Ubiquitin-dependent degradation of rpS3 consequently led to radioresistance in GBM cells. To elucidate the apoptotic role of rpS3, we analyzed the interactome of rpS3 in ΔRNF138 GBM cells. Nuclear rpS3 interacted with DNA damage inducible transcript 3 (DDIT3), leading to DDIT3-induced apoptosis in irradiated ΔRNF138 GBM cells. These results were confirmed using in vivo orthotopic xenograft models and GBM patient tissues. This study aims to clarify the role of RNF138 in GBM cells and demonstrate that rpS3 may be a promising substrate of RNF138 for the induction of GBM radioresistance, indicating RNF138 as a potential target for GBM therapy.
Apoptosis ; DNA Damage ; Fingers ; Glioblastoma ; Heterografts ; Humans ; Lung Neoplasms ; Macrophages ; NF-kappa B ; Ribosomal Proteins ; Ubiquitin ; Ubiquitination

Authors described the remote afterloading endobronchial brachytherapy (EBBT) technique using the microSelectron HDR Ir-192 and the Asan Medical Center experience. Total 28 EBBT in 9 patients were performed since November 1989 and 24 EBBT in 8 patients were emploiyed for palliation and 3 EBBT in 1 patient was treated curatively. Authors observed a significant relief of obstructive symptom with tumor regression in 7 patients out of 8 who were treated palliatively but one of them died of pulmonary congestion in 3 weeks after EBBT. One patient with prior therapy of extensive electrocautery expired within 1 day after 2nd EBBT procedure with massive hemorrhage from the lesion. EBBT procedure has been tolerable and can be performed as an outpatient
Brachytherapy* ; Chungcheongnam-do ; Electrocoagulation ; Estrogens, Conjugated (USP) ; Hemorrhage ; Humans ; Outpatients

To evaluate the effect of MVP chemotherapy and hyperfractionated radiotherapy in Stage III unresectable non small cell lung cancer (NSCLC), authors have conducted a prospective randomized study since January 1991. Stage IIIa or IIIb unresectable NSCLC patients were treated with hyperfractionated radiotherapy (120 cGy/fx BID) up to 6500 cGY following 3 cycles of induction MVP (Mitomycin C 6 mg/m2, vinblastine 6 mg/m2, Cisplatin 60 mg/m2) and randomized for either oservation or 3 cycles of maintenance MVP chemotherapy. Until August 1991, 18 patients were registered to this study. 4 cases were stage IIIa and 14 were stage IIIb. Among 18 cases 2 were lost after 2 cycles of chemotherapy, and 16 were analyzed for this preliminary report. The response rate of induction chemotherapy was 62.5%; partial response, 50% and minimal response, 12.5%. Residual tumor of the one partial responder was completely disappeared after radiotherapy. Among 6 cases who were progressed during induction chemotherapy, 4 of them were also progressed after radiotherapy. All patients were tolerated BID radiotherapy without definite increase of acute complications, compared with conventional radiotherapy group. But at the time of this report, one patient expired in two month after the completion of the radiotherapy because of treatment related complication. Although the longer follow up is needed, authors are encouraged with higher response rate and acceptable toxicity of this treatment. Authors believe that this study is worthwhile to continue.
Carcinoma, Non-Small-Cell Lung* ; Cisplatin ; Drug Therapy ; Follow-Up Studies ; Humans ; Induction Chemotherapy ; Maintenance Chemotherapy* ; Neoplasm, Residual ; Prospective Studies ; Radiotherapy* ; Small Cell Lung Carcinoma ; Vinblastine

Lung cancer study group at Asan Medical Center has conducted the second prospective study to determine the efficacy and feasibility of MVP chemotherapy with concurrent hyperfractionated radiotherapy for patients with stage III unresectable non-small cell lung cancer(NSCLC). All eligible patients with stage III unresectable NSCLC were treated with hyperfractionated radiotherapy( 120 cGy/fx BID, 6480 cGY/54fx) and concurrent 2 cycles of MVP(Motomycin C 6 mg/m2 , d2 & d29, Vinblastin 6 mg/m2, d2 & d29, Cisplatin 6 mg/m2 , d1 & d28) chemotherapy. Between Aug. 1993 and Nov. 1994, 62 patients entered this study ; 6(10%) had advanced stage IIIa and 56(90%) had IIIb disease including 1 with pleural effusion and 10 with supraclavicular metastases. Among 62 Ptients, 48(77%) completed planned therapy. Fourteen patients refused further treatment during chemoradiotherapy. Of 46 patients evaluable for response, 34(74%) showed major response including 10(22%) with complete and 24(52%) with partial responses. Of 48 patients evaluable for toxicity, 13(27%) showed grade IV hematologic toxicity but treatment delay did not exceed 5 days. Two patients died of sepsis during chemoradiotherapy. Server weight(more than 10%) occurred in 9 patients(19%) during treatment. Nine patients(19%) developed radiation pneumonitis. Six of these patients had grad I(mild) pneumonitis with radiographic changes within the treatment fields. Three other patients had grade II pneumonitis, but none of theses patients had continuous symptoms after steroid treatment. Concurrent chemoradiotherapy for patients with advanced NSCLC was well tolerated with acceptable toxicity and achieved higher response rates than the first study, but rather low compliance rate(7%) in this study is worrisome. We need to improve nutritional suppoert during treatment and to use G-CSF to improve leukopenia and if necessary, supportive care will given as in patients. Longer follow-up and larger sample size is needed to observe survival advantage.
Carcinoma, Non-Small-Cell Lung ; Chemoradiotherapy ; Chungcheongnam-do ; Cisplatin ; Compliance ; Drug Therapy* ; Follow-Up Studies ; Granulocyte Colony-Stimulating Factor ; Humans ; Leukopenia ; Lung ; Lung Neoplasms ; Neoplasm Metastasis ; Pleural Effusion ; Pneumonia ; Prospective Studies ; Radiation Pneumonitis ; Radiotherapy* ; Sample Size ; Sepsis ; Small Cell Lung Carcinoma*