PURPOSE: Dysbiosis of gut microbiota has been reported to participate in the pathogenesis of colorectal cancer, but changes in microbiota due to radiotherapy have not been studied. In this study, we tried to elucidate the changes in the microbiome in rectal cancer after chemoradiotherapy using RNA sequencing analysis.MATERIALS AND METHODS: We included 11 pairs of human rectal cancer tissues before and after irradiation between August 2016 and December 2017 and performed RNA sequencing analysis. Mapped reads to human reference genomes were used for pair-wise transcriptome comparisons, and unmapped (non-human) reads were then mapped to bacterial marker genes using PathSeq.RESULTS: At microbiome level, interindividual variability of mucosal microbiota was greater than the change in microbial composition during radiotherapy. This indicates that rapid homeostatic recovery of the mucosal microbial composition takes place short after radiotherapy. At single microbe level, Prevotella and Fusobacterium, which were identified as important causative microbes of the initiation and progression of rectal cancer were decreased by radiotherapy. Moreover, changes in Prevotella were associated with changes in the human transcriptome of rectal cancer. We also found that there was a gene cluster that increased and decreased in association with changes in microbial composition by chemoradiation.CONCLUSION: This study revealed changes in tumor-associated microbial community by irradiation in rectal cancer. These findings can be used to develop a new treatment strategy of neoadjuvant therapy for locally advanced rectal cancer by overcoming radio-resistance or facilitating radio-sensitivity.
Chemoradiotherapy ; Colorectal Neoplasms ; Dysbiosis ; Fusobacterium ; Gastrointestinal Microbiome ; Genes, vif ; Genome ; Humans ; Microbiota ; Neoadjuvant Therapy ; Prevotella ; Radiotherapy ; Rectal Neoplasms ; Sequence Analysis, RNA ; Transcriptome

PURPOSE: The bedside lung ultrasound in emergency (BLUE) protocol is an excellent diagnostic tool for acute respiratory failures requiring admission to the intensive care unit. We incorporated cardiac ultrasound in the BLUE algorithm because cardiac origin is also necessary to examine in an emergency setting. We studied the usefulness of the emergency department (ED)-BLUE protocol for patients complaining of dyspnea in an emergency department. METHODS: At first, we assessed lung sliding, artifacts (Alines and B-lines), alveolar consolidation and pleural effusion on stage I and II evaluation. Then, we checked heart to detect 3Es (Effusion, Equality, and Ejection fractions). We divided all the possible conditions into 10 categories. We compared it with final diagnosis and examined the agreements using kappa statistics. We compared the physician's level of confidence for the first impression. The 10 categories were: 1) normal or inconclusive, 2) pulmonary embolism, 3) airway disease (chronic obstructive pulmonary disease or asthma), 4) pneumothorax, 5) large pleural effusion, 6) alveolar consolidation, 7) acute pulmonary edema due to systolic congestive heart failure, 8) acute respiratory distress syndrome, 9) chronic interstitial lung disease with exacerbation, and 10) pericardial effusion with/without tamponade. RESULTS: This prospective study was performed for 172 patients over 18-years-of-age with dyspnea during a 25-month period. Kappa value between the diagnosis after ED-BLUE and final diagnosis was 0.812(p<0.001). The mean of physician's full term for LOC for the first impression before and after ED-BLUE was 3.09+/-0.83 and 4.36+/-0.70 (paired t-test, p<0.001). CONCLUSION: ED-BLUE protocol could help the emergency physician make an accurate diagnosis in patients with dyspnea in the emergent setting.
Artifacts ; Dyspnea ; Emergencies ; Heart ; Heart Failure ; Humans ; Intensive Care Units ; Lung ; Lung Diseases, Interstitial ; Lung Diseases, Obstructive ; Pericardial Effusion ; Pleural Effusion ; Pneumothorax ; Prospective Studies ; Pulmonary Edema ; Pulmonary Embolism ; Respiratory Distress Syndrome, Adult

Background: The nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathway is involved in the regulation of cellular responses to oxidative stress. Nrf2 acts as a cell protector from inflammation, cellular damage, and tumorigenesis, whereas Keap1 is a negative regulator of Nrf2. Dysregulation of the Nrf2/ Keap1 pathway results in tumorigenesis and the active metabolism of tumor cells, leading to high resistance to radiotherapy. This study aimed to evaluate the predictive role of Nrf2 and Keap1 in the radiosensitivity and prognosis of locally advanced rectal cancer (LARC). Methods: In total, 90 patients with LARC underwent surgery after preoperative chemoradiotherapy (CRT). Endoscopic biopsies from the tumors were obtained before radiation, and the Nrf2 and Keap1 expressions were assessed by immunohistochemistry. The response to therapy was evaluated after surgery following CRT according to the pathologic tumor regression grade. The disease-free survival (DFS) and overall survival rates were also documented. The association between the Nrf2 and Keap1 immunoreactivity and the clinicopathological parameters was analyzed. Results: The overexpression of the nuclear Nrf2 before CRT showed a significant correlation with better DFS. The cytoplasmic Nrf2 expression was associated with more residual tumors after radiotherapy and a more unfavorable DFS, indicating lower radiosensitivity. Conclusion CRT is an important issue in LARC and is a major aspect of treatment. Thus, the Nrf2/Keap1 expression may be a potential predictor of preoperative therapeutic resistance.The Nrf2-Keap1 modulators that interact with each other may also be effectively applicable to CRT effect in LARC.

PURPOSE: Acute aortic diseases, such as aortic dissection and aortic aneurysm, can be life-threatening vascular conditions. In this study, we compared outcomes before and after the implementation of a critical pathway (CP) for patients with acute aortic disease at the emergency department (ED). MATERIALS AND METHODS: This was a retrospective observational cohort study. The CP was composed of two phases: PRE-AORTA for early diagnosis and AORTA for prompt treatment. We compared patients who were diagnosed with acute aortic disease between pre-period (January 2010 to December 2011) and post-period (July 2012 to June 2014). RESULTS: Ninety-four and 104 patients were diagnosed with acute aortic disease in the pre- and post-periods, respectively. After the implementation of the CP, 38.7% of acute aortic disease cases were diagnosed via PRE-AORTA. The door-to-CT time was reduced more in PRE-AORTA-activated patients [71.0 (61.0, 115.0) min vs. 113.0 (56.0, 170.5) min; p=0.026]. During the post-period, more patients received emergency intervention than during the pre-period (22.3% vs. 36.5%; p=0.029). Time until emergency intervention was reduced in patients, who visited the ED directly, from 378.0 (302.0, 489.0) min in the pre-period to 200.0 (170.0, 299.0) min in the post-period (p=0.001). The number of patients who died in the ED declined from 11 to 4 from the pre-period to the post-period. Hospital mortality decreased from 26.6% to 14.4% in the post-period (p=0.033). CONCLUSION: After the implementation of a CP for patients with acute aortic disease, more patients received emergency intervention within a shorter time, resulting in improved hospital mortality.
Acute Disease ; Adult ; Aged ; Aneurysm, Dissecting/diagnosis/mortality/*surgery ; Aorta ; Aortic Aneurysm/diagnosis/mortality/*surgery ; Aortic Diseases/diagnosis/mortality/*surgery ; *Critical Pathways ; Emergency Service, Hospital/*organization & administration ; Female ; Hospital Mortality ; Humans ; Male ; Middle Aged ; Outcome and Process Assessment (Health Care) ; Postoperative Complications/mortality ; Republic of Korea/epidemiology ; Retrospective Studies ; Time Factors ; Treatment Outcome ; Vascular Surgical Procedures/*methods

Overexpression of HER2 correlates with more aggressive tumors and increased resistance to cancer chemotherapy. However, a functional comparison between the HER2high/HER3 and the HER2low/HER3 dimers on tumor metastasis has not been conducted. Herein we examined the regulation mechanism of heregulin-beta1 (HRG)-induced MMP-1 and -9 expression in breast cancer cell lines. Our results showed that the basal levels of MMP-1 and -9 mRNA and protein expression were increased by HRG treatment. In addition, HRG-induced MMP-1 and -9 expression was significantly decreased by MEK1/2 inhibitor, U0126 but not by phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294002. To confirm the role of MEK/ERK pathway on HRG-induced MMP-1 and -9 expression, MCF7 cells were transfected with constitutively active adenoviral-MEK (CA-MEK). The level of MMP-1 and -9 expressions was increased by CA-MEK. MMP-1 and -9 mRNA and protein expressions in response to HRG were higher in HER2 overexpressed cells than in vector alone. The phosphorylation of HER2, HER3, ERK, Akt, and JNK were also significantly increased in HER2 overexpressed MCF7 cells compared with vector alone. HRG-induced MMP-1 and -9 expressions were significantly decreased by lapatinib, which inhibits HER1 and HER2 activity, in both vector alone and HER2 overexpressed MCF7 cells. Finally, HRG-induced MMP-1 and MMP-9 expression was decreased by HER3 siRNA overexpression. Taken together, we suggested that HRG-induced MMP-1 and MMP-9 expression is mediated through HER3 dependent pathway and highly expressed HER2 may be associated with more aggressive metastasis than the low expressed HER2 in breast cancer cells.
Breast Neoplasms/enzymology/*genetics/*metabolism ; Butadienes/pharmacology ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/pharmacology ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MAP Kinase Signaling System ; MCF-7 Cells ; Matrix Metalloproteinase 1/*genetics/metabolism ; Matrix Metalloproteinase 9/*genetics/metabolism ; Neuregulin-1/*pharmacology ; Nitriles/pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Multimerization ; Proto-Oncogene Proteins c-akt/metabolism ; Quinazolines/pharmacology ; Receptor, erbB-2/genetics/*metabolism ; Receptor, erbB-3/*metabolism