BACKGROUND: Radiation therapy is one of the most common treatments for non-small cell lung cancer (NSCLC). However, the insensitivity of some tumor cells to radiation is one of the major reasons for the poor efficacy of radiotherapy and the poor prognosis of patients, and exploring the underlying mechanisms behind radioresistance is the key to solving this clinical challenge. This study aimed to identify the molecules associated with radioresistance in lung adenocarcinoma (LUAD), identified thyroid hormone receptor interactor 13 (TRIP13) as the main target initially, and explored whether TRIP13 is related to radioresistance in LUAD and the specific mechanism, with the aim of providing theoretical basis and potential targets for the combination therapy of LUAD patients receiving radiotherapy in the clinic. METHODS: Three datasets, GSE18842, GSE19188 and GSE33532, were selected from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (|log FC|>1.5, P<0.05) in each of the three datasets using the R 4.1.3 software, and then Venn diagram was used to find out the differentially expressed genes common to the three datasets. The screened differential genes were then subjected to protein-protein interaction (PPI) analysis and module analysis with the help of STRING online tool and Cytoscape software, and survival prognosis analysis was performed for each gene with the help of Kaplan-Meier Plotter database, and the TRIP13 gene was identified as the main molecule for subsequent studies. Subsequently, the human LUAD cell line H292 was irradiated with multiple X-rays using a sub-lethal dose irradiation method to construct a radioresistant cell line, H292DR. The radioresistance of H292DR cells was verified using cell counting kit-8 (CCK-8) assay and clone formation assay. The expression levels of TRIP13 in H292 and H292DR cells were measured by Western blot. Small interfering RNA (siRNA) was used to silence the expression of TRIP13 in H292DR cells and Western blot assay was performed. The clone formation ability and migration ability of H292DR cells were observed after TRIP13 silencing, followed by the detection of changes in the expression levels of proteins closely related to homologous recombination, such as ataxia telangiectasia mutated (ATM) protein. RESULTS: Screening of multiple GEO datasets, validation of external datasets and survival analysis revealed that TRIP13 was highly expressed in LUAD and was associated with poor prognosis in LUAD patients who had received radiation therapy. And the results of gene set enrichment analysis (GSEA) of TRIP13 suggested that TRIP13 might be closely associated with LUAD radioresistance by promoting homologous recombination repair after radiation therapy. Experimentally, TRIP13 expression was found to be upregulated in H292DR, and silencing of TRIP13 was able to increase the sensitivity of H292DR cells to radiation. CONCLUSIONS TRIP13 is associated with poor prognosis in LUAD patients treated with radiation, possibly by promoting a homologous recombination repair pathway to mediate resistance of LUAD cells to radiation.
Humans ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms/radiotherapy* ; Adenocarcinoma of Lung/radiotherapy* ; Cell Count ; Combined Modality Therapy ; ATPases Associated with Diverse Cellular Activities ; Cell Cycle Proteins

The aim of our study was to describe the radiologic findings of extensive acute lung injury associated with limited thoracic irradiation. Limited thoracic irradiation occasionally results in acute lung injury. In this condition, chest radiograph shows diffuse ground-glass appearance in both lungs and thin-section CT scans show diffuse bilateral ground-glass attenuation with traction bronchiectasis, interlobular septal thickening and intralobular smooth linear opacities.
Acute Disease ; Adenocarcinoma/radiotherapy ; Adenocarcinoma/pathology ; Adenocarcinoma/drug therapy ; Adenocarcinoma/complications* ; Carcinoma, Squamous Cell/radiotherapy ; Carcinoma, Squamous Cell/pathology ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/complications* ; Journal Article ; Human ; Lung/radiation effects* ; Lung/pathology ; Lung Neoplasms/radiotherapy ; Lung Neoplasms/pathology ; Lung Neoplasms/drug therapy ; Lung Neoplasms/complications* ; Male ; Middle Age ; Radiation Injuries/radiography ; Radiation Injuries/pathology ; Radiation Injuries/etiology* ; Thorax/radiation effects

The objective of this work was to estimate the absorbed dose of 131I to lungs in 131I therapy of differentiated thyroid carcinoma(DTC) with diffuse pulmonary metastases. Ten DTC patients with diffuse pulmonary metastases were recruited prospectively. Whole body planar scintigrams were acquired serially after administration of 7.4 GBq 131I to patients. The counts from the regions of interest of lungs and total body were obtained and converted to the percent of administered activity. The time-activity curves of lungs and total body were fit, and the areas under the curves were calculated. It was assumed that beta-eletron emissions from 131I deposited in lungs were completely absorbed by the diffuse DTC metastatic lesions, and that gamma-photon emissions from 131I deposited in the lungs and the remainder of body were irradiating the lungs. The absorbed dose to lungs was calculated according to Medical Internal Radiation Dosimetry (MIRD) formula. The median lungs absorbed dose was 0.33 Gy (range, 0.22-8.21 Gy). Based on the empiric fixed activity therapy of DTC with diffuse pulmonary metastases,the absorbed dose to lungs is low.
Adenocarcinoma ; pathology ; radiotherapy ; secondary ; Adolescent ; Adult ; Aged ; Female ; Humans ; Iodine Radioisotopes ; pharmacokinetics ; therapeutic use ; Lung ; metabolism ; Lung Neoplasms ; radiotherapy ; secondary ; Male ; Middle Aged ; Radiotherapy Dosage ; Thyroid Neoplasms ; pathology ; radiotherapy ; Young Adult

BACKGROUND: Non-small cell lung cancer is one of the most frequent cause of death due to cancer in men, and its incidence among women is rapidly increasing. Although there has been a recent surge of interest in combined modality therapy for stage III non-small cell lung cancer(NSCLC), the optimal treatment is still not well established. Thoracic irradiation has long been the gold standard for locally advanced unresectable NSCLC. However, although conventional radiotherapy(XRT) can palliate symptom and improve local control of disease, it huts at most only a modest effect on survival. Recently, cisplatin(cia-diamminedichloroplatinum ) has been reported to enhance the cell-killing effect of radiation For patients with unresectable NSCLC, cisplatin-based concurrent chemoradiotherapy(CCRT) had the advantage of therapeutic response over XRT alone and therapeutic side effect more commonly occurred in CCRT group in EORTC(European Organization for Research and Treatment of Cancer) and other trials. Objectives : We compared therapeutic response, compliance, and side effects between CCRT and XRT in patients with advanced NSCLC. Patients and METHOD: Thirty patients with biopsy-proven inoperable NSCLC were randomized to one of two treatment arms. Arm A consisted of XRT, radiotherapy for 4~6 weeks(1.8 Gy given 20~33 times, in five fractions a week), and arm B consisted of CCRT, radiotherapy for 2 weeks(3 Gy given 10 times, in five fractions a week), followed by 3 week rest period and then radiotherapy 2 more weeks(2.5 Gy given 10 timed in five fractions a week), combined with 6mg cisplatin per square meter, given daily before radiotherapy. We evaluate therapeutic response, compliance, change of performance status, side effects, and radiation pneumonitis by using the author's made scoring system. RESULTS: There was no significant difference in therapeutic response and compliance. But there was a significantly lower laboratory complication and radiation pneumonitis in CCRT group (p<0.05). There's significant negative correlation between stage and therapeutic response score in both groups(R=0.353, p<0.05). In both groups, patients with squamous cell carcinoma had a tendency to higher therapeutic response score than those with adenocarcinoma. CONCLUSION: There was. no difference between CCRT and XRT in respect to therapeutic response and compliance. But CCRT had a advantage of decreased side effects.
Adenocarcinoma ; Arm ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Cause of Death ; Chemoradiotherapy* ; Cisplatin ; Combined Modality Therapy ; Compliance ; Female ; Humans ; Incidence ; Lung Neoplasms* ; Lung* ; Male ; Radiation Pneumonitis ; Radiotherapy*

PURPOSE: p53 mutations are one of the most common genetic alterations in human lung cancer. Although the prognostic value of mutant p53 is still debated, it is widely accepted as a relatively early genetic event in the development and progression of lung cancer. Moreover, there are growing reports about an association between smoking and p53 mutation, suggesting that the p53 gene could be a target of the smoking associated carcino- genesis in the lung cancer. MATERIALS AND METHODS: Surgically resected 89 primary non-small cell lung cancers were obtained from May of 1995 to May of 1997. p53 expression and Ki-67 expression were measured by immunohistochemistry, and each p53 expression and smoking amount were compared with Ki-67 expression and other clinical prognostic factors. RESULTS: Positive p53 expressions were found in 52 (58%) specimens, including 38 (69%) squamous cell carcinomas, 11 (39%) adenocarcinomas, and 3 (50%) large cell carcinomas, and closely associated with male and squamous cell carcinoma. Also close correlation was observed between smoking amount and p53 expression by the regression analysis. But p53 and Ki-67 expression showed no associations in pathologic stage and survival, and there was no association between p53 expression and survival after adjuvant radiotherapy. CONCLUSION: Smoking seems to affect p53 mutations in non-small cell lung cancer, and additional efforts are needed to evaluate the carcinogesis of lung cancer.
Adenocarcinoma ; Carcinoma, Large Cell ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Genes, p53 ; Humans ; Immunohistochemistry ; Lung Neoplasms ; Male ; Radiotherapy, Adjuvant ; Small Cell Lung Carcinoma* ; Smoke* ; Smoking*

PURPOSE: This study was designed to analyze the clinical characteristics of patients with immediate distant metastasis after preoperative chemoradiotherapy for locally advanced rectal cancer and to help select patients for preoperative chemoradiotherapy. METHODS: Two hundred eight patients, who underwent preoperative chemoradiotherapy for locally advanced rectal cancer, were included. Patients were excluded from the study if they had tumor types other than an adenocarcinoma, prior chemotherapy, radiotherapy, or hereditary nonpolyposis colorectal cancer. The clinicopathological characteristics of patients with distant metastasis immediately after preoperative chemoradioterapy were compared with those of patients without distant metastasis. RESULTS: Distant metastases immediately after preoperative chemoradiotherapy were identified in 15 patients (7.2%). The liver was the most common site of metastasis (8/15), followed by peritoneal seeding (4), the lung (2), bone (1), and the aortocaval lymph node (1). Age, sex, chemotherapy regimen used, and primary tumor response for patients with distant metastases were similar to those for patients without distant metastasis. In patients with immediate distant metastasis, pre-chemoradiotherapy CEA was significantly higher (11.1 vs. 7.4 ng/ml; P= 0.003). CONCLUSIONS: Immediate distant metastasis after preoperative chemoradiotherapy is associated with pre-chemoradiotherapy CEA level. A careful work-up is necessary when pre-chemoradiotherapy CEA is higher than the normal range.
Adenocarcinoma ; Chemoradiotherapy* ; Colorectal Neoplasms, Hereditary Nonpolyposis ; Drug Therapy ; Humans ; Liver ; Lung ; Lymph Nodes ; Neoplasm Metastasis* ; Radiotherapy ; Rectal Neoplasms* ; Reference Values

From Nov. 1983 through Jan. 1986, 43 patients with nonsmall cell lung cancer were treated by radiation therapy at Inje Medical College Paik Hospital. 38 patients were available for the analysis of this study. 33 patients received definite irradiation with curative intent, while 5 patients received postoperative irradion. Chemotherapy was added in 12 patients before, during and after radio-therapy. 28 patients were squamous cell carcinoma and 10 patients were adenocarcinoma. There were 29 men and 9 women (median age, 58 years; range 34 to 74 years). Stage 1 was 1 patients, Stage 11, 7 patient, and Stage 111, 30 patients. Among 33 patients who received radiotherapy with curative intent, follow up radiological study revealed complete response in 12 patients (36%), partial response, in 9 patients (27%), and minimal response, in 5 patients (15%), while 7 patients (21%) were nonresponders. Median survival for all patients was 6.9 months; squamous cell carcinoma, 7.3 months, adenocarcinoma, 5.9 months. Responders survived median 7 months, while nonresponders survived median 1.9 months. Improved complete response rate and survival were shown in high radiation dose group. As prognostic factors, age, initial performance status, sex, histology and tumor location were evaluated.
Adenocarcinoma ; Age Factors ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Drug Therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Radiotherapy*

Sorafenib is an emerging therapeutic option for radioactive iodine (RAI)-refractory differentiated thyroid carcinoma. However, the effects of sorafenib as an adjuvant treatment following surgery or radiation on brain metastases from poorly differentiated thyroid carcinoma (PDTC) have never been reported. A 52-year-old patient underwent total thyroidectomy for follicular thyroid carcinoma. Despite high-dose RAI therapy, a neck mass and lung metastases were developed. PDTC was diagnosed by neck mass removal. During adjuvant external beam radiation therapy (EBRT) to the neck, brain metastases developed. After palliative EBRT for brain metastases, the brain tumor size decreased but lung metastases markedly progressed. Off-label sorafenib was used to treat progressive multiple metastatic lesions. Over five months of sorafenib treatment, the sum of the longest diameters for target lesions was decreased by 45% in brain and 13% in lung. Sorafenib can be considered a new adjuvant therapeutic option for metastatic brain lesions from PDTC after EBRT.
Adenocarcinoma, Follicular ; Brain Neoplasms ; Brain* ; Humans ; Iodine ; Lung ; Middle Aged ; Neck ; Neoplasm Metastasis* ; Radiotherapy* ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

From December 1989 to February 1993, 108 patients with Non-Small Cell Lung Cancers(NSCLC) were studied retrospectively to evaluate radiotherapeutic significance of serum levels of NSE. We considered elevated serum neuron specific pathologic evaluation revealed 86 squamous cell carcinomas, 11 adenocarcinomas, 3 large cell carcinomas, 3 mucoepidermoid carcinomas, and 5 unknown pathology. Eight patients had stageI, 40 stage III A, and 60 stageIII B. S-NSE level greater than 15 ng/ml was considered as elevated, and below this considered as normal. All patients received radiotherapy as primary treatment modality. The responders to radiotherapy had significantly higher mean S-NSE level than on-responders (28.5 ng/ml vs 20 ng/ml, p=0.01). Overall 2-year survival rate (YSR) was 23.6%. According to radiotherapy response, 2 YSR for patients with CR, PR, and NR were 39.2%, 28.6%, and 6.2% respectively (p=0.001). 2 YSR for patients with elevated and normal S-NSE were 14.6% and 31.7%(p=0.02). The patients with NR showed no difference in survival according to S-NSE level. When we considered all patients, S-NSE level showed no significant impact on response. But for squamous cell cardinomas alone, patients with elevated S-NSE had more patients with higher nodal stage. Based on our and other data, NSCLSC with neuroendocrine features have different response to treatment and clinical behavior compared to other NSCLSC. Thus, this subgroup may need different treatment modality, and S-NSE level may have prognostic significance.
Adenocarcinoma ; Carcinoma, Large Cell ; Carcinoma, Mucoepidermoid ; Carcinoma, Squamous Cell ; Humans ; Lung Neoplasms* ; Lung* ; Neurons ; Pathology ; Phosphopyruvate Hydratase ; Radiotherapy ; Retrospective Studies ; Survival Rate

From Jan. 1984 to Dec. 1986, 90 patients with lung cancer were treated t the Department of Radiation Therapy in Hanyang University Hospital. Histopathologically, 67 cases of them were the squamous cell carcinoma, 7 cases were the adenocarcinoma, 4 cases were the large cell undifferentiated carcinoma and 12 cases were the small cell carcinoma. Among the 78 patients with non small cell carcinoma, 50 patients had received radiation dosage above 4000 cgy. 40 patient had follow up from 17 months to 53 months. The complete response rate was 7.3% and partial response rate was 68.3%. Overall survival at 1,2 and 3 years were 47.5%, 23.5% and 6.3% respectively. None was survived longer than 38 months. Median survival was 12.2 month for 40 patient and 9 month for stage III, M1 group and 9.5 month for stage III, M0 group. In M1 patient no survival was seen after 2 years while in M0 patient 23.3% survival was seen.
Adenocarcinoma ; Carcinoma ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Small Cell ; Carcinoma, Squamous Cell ; Follow-Up Studies ; Humans ; Lung Neoplasms ; Radiation Dosage ; Radiotherapy