Anti-epidermal growth factor receptor (EGFR) therapy has been tried in triple negative breast cancer (TNBC) patients without evaluation of molecular and clinical predictors in several randomized ...clinical studies. Only fewer than 20% of metastatic TNBCs showed response to anti-EGFR therapy. In order to increase the overall response rate, first step would be to classify TNBC into good or poor responders according to oncogenic mutation profiles. This study provides the molecular characteristics of TNBCs including EGFR gene copy number changes and mutation status of EGFR and KRAS gene in Korean TNBC patients. Mutation analysis for EGFR, KRAS, BRAF and TP53 from a total of 105 TNBC tissue samples was performed by direct sequencing, peptide nucleic acid-mediated PCR clamping method and real-time PCR. Copy number changes of EGFR gene were evaluated using multiplex ligation-dependent probe amplification. Out of all 105 TNBCs, 15.2% (16/105) showed EGFR copy number changes. Among them, increased or decreased EGFR copy number was detected in 13 (5 single copy gain, 2 amplification and 4 high-copy number amplification) and 3 cases (3 hemizygous deletion), respectively. The mutation frequencies of KRAS, EGFR and TP53 gene were 1.9% (G12V and G12D), 1.0% (exon 19 del) and 31.4%, respectively. There was no BRAF V600E mutation found. Future studies are needed to evaluate the clinical outcomes of TNBC patients who undergo anti-EGFR therapy according to the genetic status of EGFR.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. We analyzed the prognostic impact of LOXL2 for breast cancer patients and investigated the role of LOXL2 ...in breast cancer cell lines. Immunohistochemical study of LOXL2 expression was done in samples from 309 patients. Survival analysis was performed using log-rank test and Cox regression hazard model. After identification of LOXL2 expression in breast cancer cell lines, we performed matrigel invasion and wound-healing assays with LOXL2-silenced cell lines. In the human study, LOXL2 was expressed in 16.2 % of patients. Comparing the LOXL2-positive versus negative groups, there was a significantly higher proportion of estrogen receptor-negative patients (54.0 vs. 37.0 %, respectively;
p
= 0.029) and triple-negative patients (34.0 vs. 18.0 %;
p
= 0.022) in the positive group. In multivariate analysis for overall survival and metastasis-free survival, positive LOXL2 was demonstrated as a poor prognostic factor (HR 2.27 and 2.10, respectively). In vitro study indicated that LOXL2 silencing induces a mesenchymal–epithelial transition-like process in basal cell lines (MDA-MB-231 and BT549) associated with decreased invasive and migratory properties. These clinical and preclinical data confirm that higher LOXL2 expression is associated with invasiveness of basal-like breast cancer cells and lower survival of breast cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in breast cancer.
Bone is the most frequent site of metastasis among breast cancer patients. We investigated prognostic factors affecting survival following bone-only metastasis in breast cancer patients.
The medical ...records of breast cancer patients who were treated and followed at Gangnam Severance Hospital retrospectively reviewed to identify patients with bone-only metastasis.
The median time from the diagnosis of bone-only metastasis to the last follow-up or death was 55.2 95% confidence interval (CI), 38.6-71.9 months. The Kaplan-Meier overall survival estimate at 10 years for all patients was 34.9%. In the multivariate Cox regression model, bisphosphonate treatment hazard ratio=0.18; 95% CI, 0.07-0.43, estrogen receptor positivity (hazard ratio=0.51; 95% CI, 0.28-0.94), and solitary bone metastasis (hazard ratio=0.32; 95% CI, 0.14-0.72) were significantly associated with longer overall survival in the bone-only recurrence group. Among the treatment modalities, only bisphosphonate treatment was identified as a significant prognostic factor.
Identifying the factors influencing breast cancer mortality after bone-only metastasis will help clarify the clinical course and improve the treatment outcome for patients with breast cancer and bone-only metastasis. Bisphosphonates, as a significant prognostic factor, warrant further investigation.
Purpose: Pulmonary rehabilitation (PR) is a well-established treatment for chronic obstructive pulmonary disease (COPD). The standard protocol for PR requires frequent hospital visits, which can be ...difficult for patients. We performed this study to assess whether unsupervised home-based PR (HBPR) is effective for patients with COPD. Patients and Methods: After assessing the outcome data, including the results of a COPD assessment test (CAT); the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index; a spirometry; the modified Medical Research Council (mMRC) dyspnea scale; and the 6-min walking test (6MWT), specialists imparted 1-hour education to patients regarding unsupervised HBPR at the baseline visit. This included methods for breathing, inhaler use, stretching, and exercise. On reviewing diaries after 8 weeks from the first visit, patients who exercised at least thrice per week were classified as the compliant group and the others were categorized as the noncompliant group. Changes in the outcomes were compared between the compliant and noncompliant groups. Results: A total of 41 patients were enrolled in this study; for 8 weeks of unsupervised HBPR, there were significant improvements in CAT scores (-4.62+ or -4.61 vs 2.40+ or -6.73; P=0.002), BODE index (-1.00+ or -1.06 vs -0.20+ or -0.56; P=0.01), and forced expiratory volume in 1 s (0.05+ or -0.19 vs -0.09+ or -0.16; P=0.02) among patients in the compliant group, compared with the noncompliant group. Moreover, their CAT (16.46+ or -7.80 vs 11.85+ or -7.23; P=0.03) and mMRC scores (2.54+ or -0.76 vs 1.81+ or -0.63; P=0.001) improved significantly after 8 weeks, compared with those at baseline. On the other hand, patients in the noncompliant group showed no significant improvement in any of the outcomes. Conclusion: In this study, compliant patients with unsupervised HBPR achieved favorable outcomes in 8 weeks. Thus, we recommend unsupervised HBPR for patients with COPD, even when regular hospital visits for PR are not possible. Trial Registration: NCT03754881. Keywords: chronic obstructive lung disease, chronic obstructive lung disease assessment test, home-based pulmonary rehabilitation, modified Medical Research Council, pulmonary rehabilitation
Wnt signaling has recently emerged as a key factor in controlling stem cell expansion. In contrast, we show here that Wnt/β-catenin signal activation in emigrating neural crest stem cells (NCSCs) has ...little effect on the population size and instead regulates fate decisions. Sustained β-catenin activity in neural crest cells promotes the formation of sensory neural cells in vivo at the expense of virtually all other neural crest derivatives. Moreover, Wnt1 is able to instruct early NCSCs (eNCSCs) to adopt a sensory neuronal fate in a β-catenin-dependent manner. Thus, the role of Wnt/β-catenin in stem cells is cell-type dependent.
Purpose: Sounds play important roles in promoting and disrupting sleep. How our brain processes sleep-related sounds and individual differences in processing sleep-related sounds must be determined ...to understand the role of sound in sleep. We investigated neural responses to sleep-related sounds and their associations with cognitive appraisals of sleep. Participants and Methods: Forty-four healthy adults heard sleep-related and neutral sounds during functional magnetic resonance imaging using a 3T scanner. They also completed the Dysfunctional Beliefs and Attitudes about Sleep (DBAS) questionnaire, which was used to assess cognitive appraisals of sleep. We conducted a voxel-wise whole-brain analysis to compare brain activation in response to sleep-related and neutral sounds. We also examined the association between the DBAS score and brain activity in response to sleep-related sounds (vs neutral sounds) using region of interest (ROI) and whole-brain correlation analyses. The ROIs included the anterior cingulate cortex (ACC), anterior insula (AI), and amygdala. Results: The whole-brain analysis revealed increased activation in the temporal regions and decreased activation in the ACC in response to sleep-related sounds compared to neutral sounds. The ROI and whole-brain correlation analyses showed that higher DBAS scores, indicating a negative appraisal of sleep, were significantly correlated with increased activation of the ACC, right medial prefrontal cortex, and brainstem in response to sleep-related sounds. Conclusion: These results indicate that the temporal cortex and ACC, which are implicated in affective sound processing, may play important roles in the processing of sleep-related sounds. The positive association between the neural responses to sleep-related sounds and DBAS scores suggest that negative and dysfunctional appraisals of sleep may be an important factor in individual differences in the processing of sleep-related sounds. Keywords: anterior cingulate cortex, appraisal, functional magnetic resonance imaging, sleep-related sounds
Purpose: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease presenting as multiple phenotypes, such as declining lung function, emphysema, or persistent airflow limitation caused ...by several risk factors, including cigarette smoking and air pollution. The inherent complexity of COPD phenotypes propounds difficulties for accurate diagnosis and prognosis. Although metabolomic profiles on COPD have been reported, the role of metabolism in COPD-related phenotypes is yet to be determined. In this study, we investigated the association between plasma sphingolipids and amino acids, and between COPD and COPD- related phenotypes in a Korean cohort. Patients and Methods: Blood samples were collected from 120 patients with COPD and 80 control participants who underwent spirometry and quantitative computed tomography. The plasma metabolic profiling was carried out using LC-MS/MS analysis. Results: Among the evaluated plasma sphingolipids, an increase in the metabolism of two specific sphingomyelins, SM (d18:1/24:0) and SM (d18:1/24:1) were significantly associated with COPD. There was no significant correlation between any of the SMs and the emphysema index, FVC and FEV.sub.1 in the COPD cohort. Meanwhile, Cer (d18:1/18:0) and Cer (d18:1/24:1) were significantly associated with reduced FEV.sub.1. Furthermore, the levels of several amino acids were altered in the COPD group compared to that in the non-COPD group; glutamate and alpha AAA were substantial associated with emphysema in COPD. Kynurenine was the only amino acid significantly associated with reduced FEV1 in COPD. In contrast, there was no correlation between FVC and the elevated metabolites. Conclusion: Our results provide dysregulated plasma metabolites impacting COPD phenotypes, although more studies are needed to explore the underlying mechanism related to COPD pathogenesis. Keywords: targeted sphingolipids, amino acids, sub-phenotypes, lung function
Smoking-related interstitial lung disease (ILD) consists of a heterogeneous group of disorders that are considered a distinct entity. The 2013 American Thoracic Society and European Respiratory ...Society recommendations classified respiratory bronchiolitis (RB)/RB-ILD and desquamative interstitial pneumonia (DIP) as smoking-related idiopathic interstitial pneumonias (IIPs). The overlapping histopathological and radiological patterns of smoking-related IIPs must be considered. Overlap patterns of smoking-related IIPs are not easily classified as a single disorder. The initial radiological manifestation and follow-up changes are heterogeneous, even when diagnosed pathologically as RB or DIP. Therefore, a clinical-radiological-pathological consensus is important in the diagnosis of smoking-related IIPs, and long-term evaluation is essential to monitor the morphological changes in these patients. In this article, we reviewed the clinical, radiological, and pathological findings, and also the changes in radiological manifestations of smoking-related IIPs over time.
The prognosis of breast cancer has been consistently improving. We analyzed our cohort of breast cancer patients with a long-term follow up at a single center over time.
A total of 1889 patients with ...known cancer stages were recruited and analyzed between January 1991 and December 2005. Patients were classified according to the time periods (1991-1995; 1996-2000; 2001-2005). To determine intrinsic subtypes, 858 patients whose human epidermal growth receptor-2 status and Ki67 were reported between April 2004 and December 2008 were also analyzed.
At a median follow up of 9.1 years, the 10-year overall survival (OS) rate was 80.5% for the entire cohort. On multivariate analysis for OS and recurrence-free survival (RFS), the time period was demonstrated to be a significant factor independent of conventional prognostic markers. In the survival analysis performed for each stage (I to III), OS and RFS significantly improved according to the time periods. Adoption of new agents in adjuvant chemotherapy and endocrine therapy was increased according to the elapsed time. In the patients with known subtypes, OS and RFS significantly differed among the subtypes, and the triple-negative subtype showed the worst outcome in stages II and III.
In the Korean breast cancer cohort with a long-term follow up, our data show an improved prognosis over the past decades, and harbor the contribution of advances in adjuvant treatment. Moreover, we provided new insight regarding comparison of the prognostic impact between the tumor burden and subtypes.
Liver resection with colorectal liver metastasis widely accepted and has been considered safe and effective therapeutic option. However, the role of liver resection in breast cancer with liver ...metastasis is still controversial. Therefore, we reviewed the outcome of liver resection in breast cancer patients with liver metastases in a single hospital experiences.
Between January 1991 and December 2006, 2176 patients underwent breast cancer surgery in Gangnam Severance Hospital. Among these patients, 110 cases of liver metastases were observed during follow-up and 13 of these patients received liver resection with potential feasibility to achieve an R0 resection.
The median time interval between initial breast cancer and detection of liver metastasis was 62.5 months (range, 13-121 months). The 1-year and 3-year overall survival rates of the 13 patients with liver resection were 83.1% and 49.2%, respectively. The 1-year and 3-year overall survival rates of patients without extrahepatic metastasis were 83.3% and 66.7% and those of patients with extrahepatic metastasis were 80.0% and 0.0%, respectively (p=0.001).
Liver resection for metastatic breast cancer results in improved patient survival, particularly in patients with solitary liver metastasis and good general condition.
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