Radiation Induced Lung Damage: Mechanisms and Clinical Implications

Radiation therapy is one of most important therapeutic modalities for thoracic malignancies. However, radiation-induced lung damage, such as radiation pneumonitis or fibrosis, is a main dose-limiting factor when irradiating the thorax. The radiation over threshold dose results in damage to pneumocytes and endothelial cells and the inflammatory changes following the damage lead to necrosis of damaged tissue, which are then replaced by fibrotic tissue. There is diffuse lung damage and edema on histopathologic inspection; however, the tissue damage and edema is not specific for radiation injury and we are far from a reliable pathogenic model. Many parameters have been evaluated for predicting radiation pneumonitis and the most consistent predictor is cumulative radiation dose to normal lung tissue. The combination of chemotherapy probably increases the incidence and severity of radiation pneumonitis; however, this is not clear. Efforts to reduce the radiation dose to normal lung tissue using new radiotherapy techniques can reduce the incidence and severity of radiation- induced lung damage. Many biological agents have been tried to prevent and treat radiation pneumonitis; however, more data is needed

Klebsiella pneumoniae is able to trigger epithelial-mesenchymal transition process in cultured airway epithelial cells

The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells

Loco-regional outcomes of adjusted breast radiotherapy with conventional fractionation after breast conserving surgery: De-escalation of whole breast irradiation dose

We compared the cumulative incidence of ipsilateral breast tumor recurrence (IBTR) between 2 whole breast irradiation (WBI) dose range with conventional fractionation.We retrospectively reviewed 1122 patients who received WBI at 2 institutions between 2004 and 2012. One institution delivered WBI 41.4 to 45 Gy followed by boost 14 to 18 Gy (adjusted group), while the other delivered WBI 50 to 50.4 Gy followed by boost 10 Gy (standard group).The median follow-up period was 85 months. The 10-year cumulative incidence in all patients was 6.1% (95% confidence interval [CI]: 4.3%-8.4%) for IBTR and 3.0% (95% CI: 1.7%-4.8%) for regional recurrence. The 10-year cumulative incidence of IBTR was not significantly influenced by WBI dose (6.3% in the adjusted group vs 5.2% in the standard group, P = .136). Comparable IBTR rates between the 2 groups were observed regardless of clinical and pathological factors. The WBI dose was not significantly associated with the 10-year cumulative incidence of regional recurrence in these groups (3.5% in the adjusted group vs 0.5% in the standard group, P = .214).De-escalated WBI doses while intensifying tumor bed boost did not compromise local and regional outcomes compared to standard group

Psychiatric comorbidities among endometrial cancer survivors in South Korea: a nationwide population-based, longitudinal study

OBJECTIVE: This longitudinal study aimed to analyze the prevalence of mental disorders in endometrial cancer survivors in South Korea. METHODS: We assessed mental disorders in a nationwide cohort of 8,155 patients who were diagnosed with endometrial cancer between January 1, 2010, and December 31, 2014. We categorized the prevalence of mental disorders based on age and time of diagnosis. RESULTS: Based on the first diagnosis, mental disorders were identified in 567 (7.0%) among patients with endometrial cancer. Of those patients, 249 (43.9%) were diagnosed with depression and 248 (43.7%) with anxiety. The overall incidence of mental disorders peaked within 2 months after hysterectomy. The rate of stress reaction/adjustment disorder increased most rapidly among the mental disorders after hysterectomy. While depression rates were relatively high among younger individuals (under 50 years), anxiety was more frequent in older people (over 50 years old). In the entire prescription (n=6,034), depression had the highest incidence (n=3,801), followed by anxiety (n=1,774). Over 89% (n=5,362) of the mental disorder treatment claims were from psychiatric medical departments. CONCLUSION: Mental disorders showed different prevalence patterns among endometrial cancer survivors depending on patient age and the nature of the disease. Intensive and personalized management of distress is necessary for endometrial cancer survivors

Characterization of a putative NsrR homologue in Streptomyces venezuelae reveals a new member of the Rrf2 superfamily

Members of the Rrf2 superfamily of transcription factors are widespread in bacteria but their functions are largely unexplored. The few that have been characterized in detail sense nitric oxide (NsrR), iron limitation (RirA), cysteine availability (CymR) and the iron sulfur (Fe-S) cluster status of the cell (IscR). In this study we combined ChIP-seq with in vitro biochemistry to characterize a putative NsrR homologue in the model organism Streptomyces venezuelae. ChIP seq analysis revealed that rather than regulating the nitrosative stress response like NsrR, Sven6563 binds to a different, much larger regulon of genes with a diverse range of functions, including a range of regulators, genes required for glutamine synthesis, NADH/NAD(P)H metabolism, as well as general DNA/RNA and amino acid/protein turn over. Our biochemical experiments further show that Sven6563 has a [2Fe-2S] cluster and that the switch between oxidized and reduced cluster controls its DNA binding activity in vitro. To our knowledge, both the sensing domain and the target gene regulon are novel for an Rrf2 protein, suggesting Sven6563 represents a new member of the Rrf2 superfamily. Given the redox sensitivity of its Fe-S cluster we have tentatively named the protein RsrR for Redox sensitive response Regulator

London 2012 Paralympic swimming: Passive drag and the classification system

Background: The key difference between the Olympic and Paralympic Games is the use of classification systems within Paralympic sports to provide a fair competition for athletes with a range of physical disabilities. In 2009, the International Paralympic Committee mandated the development of new, evidence-based classification systems. This study aims to assess objectively the swimming classification system by determining the relationship between passive drag and level of swimming-specific impairment, as defined by the current swimming class. Methods: Data were collected on participants at the London 2012 Paralympic Games. The passive drag force of 113 swimmers (classes 3-14) was measured using an electro-mechanical towing device and load cell. Swimmers were towed on the surface of a swimming pool at 1.5 m/s while holding their most streamlined position. Results: Passive drag ranged from 24.9 to 82.8 N; the normalised drag (drag/mass) ranged from 0.45 to 1.86 N/kg. Significant negative associations were found between drag and the swimming class (τ=-0.41, p<0.01) and normalised drag and the swimming class (τ=-0.60, p<0.01). The mean difference in drag between adjacent classes was inconsistent, ranging from 0 N (6 vs 7) to 11.9 N (5 vs 6). Reciprocal Ponderal Index (a measure of slenderness) correlated moderately with normalised drag (rP=-0.40, p<0.01). Conclusions: Although swimmers with the lowest swimming class experienced the highest passive drag and vice versa, the inconsistent difference in mean passive drag between adjacent classes indicates that the current classification system does not always differentiate clearly between swimming groups

Metabolic comorbidities and medical institution utilization among breast cancer survivors: a national population-based study

BACKGROUND/AIMS: We investigated metabolic comorbidity status and patterns of medical institution utilization among breast cancer survivors using medical claims data from the Health Insurance Review and Assessment Service (HIRA). METHODS: Using claims data obtained from the HIRA, we selected breast cancer survivors between 2010 and 2015. Descriptive statistics were calculated to determine the frequency of metabolic comorbidities, as well as to analyze patterns of medical institution utilization in accordance with disease status. RESULTS: A total of 89,953 breast cancer survivors were identified. Among these, 12,364 (13.7%) had hypercholesterolemia, 20,754 (23.1%) had hypertension (HTN), and 11,102 (12.3%) had diabetes mellitus (DM). In particular, more than half of breast cancer survivors older than 60 years had HTN, and other diseases sharply increased beginning at age 50 years. For HTN, a total of 531,292 claims were submitted; more than 80% (n = 473,737) were from primary medical institutions, whereas only 2.4% (n = 12,551) were from tertiary medical institutions. The number of claims submitted for DM was 231,526; those from primary medical institutions accounted for 68.5% (n = 158,566), whereas claims from tertiary medical institutions accounted for 12.0% (n = 27,693). In subgroup analyses, the utilization of secondary and tertiary medical institutions was higher among patients with severe diseases and those diagnosed following their breast cancer diagnosis. CONCLUSION: More than 10% of breast cancer survivors were diagnosed with a metabolic comorbidity. Through analysis of medical institution utilization patterns, we ascertained that a communication system linking secondary and tertiary medical institutions with primary medical institutions is needed

Influenza Among Breast Cancer Survivors in South Korea: A Nationwide Population-Based Study

BACKGROUND/AIM: In this study, we analyzed the prevalence of influenza disease in breast cancer survivors using claims data from the Health Insurance Review and Assessment Service (HIRA) in South Korea. PATIENTS AND METHODS: We defined influenza among a nationwide cohort of 87,843 patients who were diagnosed with breast cancer and underwent surgery from January 1, 2010 to December 31, 2014, based on HIRA claim data. Descriptive statistics were calculated to estimate the frequency of influenza disease using diagnostic code and utilization pattern at medical institutions. RESULTS: Two thousand four hundred breast cancer survivors (2.7%) were diagnosed with influenza. The overall frequency of influenza increased from November (n=98) and peaked in February (n=1,745). Over 60% (2,693) of claims for influenza disease treatment were in the clinic, whereas general hospitals accounted for 22.0% (873). Among 3,967 claims, admission rate was 7.6% (n=301) and the average length of hospitalization was 4.7 days. Elderly breast cancer survivors over 70 years old had the longest length of hospitalization at 5.9 days. CONCLUSION: Breast cancer survivors are more susceptible to influenza than non-cancer survivors. It is important not only to raise the vaccination rate among young cancer survivors, but also to quickly identify symptoms and begin treatment for flu in elderly cancer survivors

Protective effects of Korean red ginseng against radiation-induced apoptosis in human HaCaT keratinocytes.

Radiation-induced oral mucositis is a dose-limiting toxic side effect for patients with head and neck cancer. Numerous attempts at improving radiation-induced oral mucositis have not produced a qualified treatment. Ginseng polysaccharide has multiple immunoprotective effects. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in the human keratinocyte cell line HaCaT and in an in vivo zebrafish model. Radiation inhibited HaCaT cell proliferation and migration in a cell viability assay and wound healing assay, respectively. KRG protected against these effects. KRG attenuated the radiation-induced embryotoxicity in the zebrafish model. Irradiation of HaCaT cells caused apoptosis and changes in mitochondrial membrane potential (MMP). KRG inhibited the radiation-induced apoptosis and intracellular generation of reactive oxygen species (ROS), and stabilized the radiation-induced loss of MMP. Western blots revealed KRG-mediated reduced expression of ataxia telangiectasia mutated protein (ATM), p53, c-Jun N-terminal kinase (JNK), p38 and cleaved caspase-3, compared with their significant increase after radiation treatment. The collective results suggest that KRG protects HaCaT cells by blocking ROS generation, inhibiting changes in MMP, and inhibiting the caspase, ATM, p38 and JNK pathways

Effects of a Smartphone Application on Breast Self-Examination: A Feasibility Study

Objectives: The aims of this study were to develop a smartphone application to encourage breast self-examination (BSE), and to evaluate the effects of this application in terms of modifying BSE behavior. Methods: A smartphone application, based on the Android OS, was developed with functions including a BSE date alarm, a reminder to encourage mother and daughter to practice BSE together, record keeping, and educational content with video clips. Females aged 19 and over were enrolled to evaluate the effectiveness of the application. Two series of questionnaires were carried out (before and after use of the application) by e-mail, telephone, and face-to-face interviews between July and September 2012. Results: Forty-five subjects were enrolled in the study (age 29.5-5.9 years). Of the participants, only 28 (62.2%) had ever practiced BSE and only one of these (2.2%) was carried out at the appropriate time, based on the results of the baseline survey. After using the application, the number of participants practicing BSE increased from 28 to 32 (62.2% to 71.1%, p = 0.503). In subgroup analysis (age < 30 years), the number of participants using BSE increased from 8 to 18 (36.4% to 81.8%, p = 0.002), and the number of those using it at the appropriate time rose from 1 to 15 (2.2% to 33.3%, p < 0.001). Conclusions: The use of the developed smartphone application increased BSE in females younger than 30 years. To confirm the long-term benefits of the mobile application, additional studies must be carried out