Radiation-induced immune responses: mechanisms and therapeutic perspectives.

Recent advancement in the radiotherapy technology has allowed conformal delivery of high doses of ionizing radiation precisely to the tumors while sparing large volume of the normal tissues, which have led to better clinical responses. Despite this technological advancement many advanced tumors often recur and they do so within the previously irradiated regions. How could tumors recur after receiving such high ablative doses of radiation? In this review, we outlined how radiation can elicit anti-tumor responses by introducing some of the cytokines that can be induced by ionizing radiation. We then dis-cuss how tumor hypoxia, a major limiting factor responsible for failure of radiotherapy, may also negatively impact the anti-tumor responses. In addition, we highlight how there may be other populations of immune cells including regulatory T cells (Tregs), mye-loid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that can be recruited to tumors interfering with the anti-tumor immunity. Finally, the impact of irradiation on tumor hypoxia and the immune responses according to different radio-therapy regimen is also delineated. It is indeed an exciting time to see that radiotherapy is being combined with immunotherapy in the clinic and we hope that this review can add an excitement to the field.11Yscopuskc

DNA methylation loss promotes immune evasion of tumours with high mutation and copy number load

Mitotic cell division increases tumour mutation burden and copy number load, predictive markers of the clinical benefit of immunotherapy. Cell division correlates also with genomic demethylation involving methylation loss in late-replicating partial methylation domains. Here we find that immunomodulatory pathway genes are concentrated in these domains and transcriptionally repressed in demethylated tumours with CpG island promoter hypermethylation. Global methylation loss correlated with immune evasion signatures independently of mutation burden and aneuploidy. Methylome data of our cohort (n = 60) and a published cohort (n = 81) in lung cancer and a melanoma cohort (n = 40) consistently demonstrated that genomic methylation alterations counteract the contribution of high mutation burden and increase immunotherapeutic resistance. Higher predictive power was observed for methylation loss than mutation burden. We also found that genomic hypomethylation correlates with the immune escape signatures of aneuploid tumours. Hence, DNA methylation alterations implicate epigenetic modulation in precision immunotherapy

Prevalence of Clonorchis sinensis Metacercariae in Freshwater Fish from Three Latitudinal Regions of the Korean Peninsula

A large-scale survey was conducted to investigate the infection status of fresh water fishes with Clonorchis sinensis metacercariae (CsMc) in 3 wide regions, which were tentatively divided by latitudinal levels of the Korean peninsula. A total of 4,071 freshwater fishes were collected from 3 regions, i.e., northern (Gangwon-do: 1,543 fish), middle (Chungcheongbuk-do and Gyeongsangbuk-do: 1,167 fish), and southern areas (Jeollanam-do, Ulsan-si, and Gyeongsangnam-do: 1,361 fish). Each fish was examined by the artificial digestion method from 2003 to 2010. In northern areas, only 11 (0.7%) fish of 2 species, Pungtungia herzi and Squalidus japonicus coreanus from Hantan-gang, Cheolwon-gun, Gangwon-do were infected with av. 2.6 CsMc. In middle areas, 149 (12.8%) fish were infected with av. 164 CsMc. In southern areas, 538 (39.5%) fish were infected with av. 159 CsMc. In the analysis of endemicity in 3 regions with an index fish, P. herzi, 9 (6.2%) of 146 P. herzi from northern areas were infected with av. 2.8 CsMc. In middle areas, 34 (31.8%) of 107 P. herzi were infected with av. 215 CsMc, and in southern areas, 158 (92.9%) of 170 P. herzi were infected with av. 409 CsMc. From these results, it has been confirmed that the infection status of fish with CsMc is obviously different among the 3 latitudinal regions of the Korean peninsula with higher prevalence and burden in southern regions

Selection of internal reference genes for SYBR green qRT-PCR studies of rhesus monkey (Macaca mulatta) tissues

<p>Abstract</p> <p>Background</p> <p>The rhesus monkey (<it>Macaca mulatta</it>) is a valuable and widely used model animal for biomedical research. However, quantitative analyses of rhesus gene expression profiles under diverse experimental conditions are limited by a shortage of suitable internal controls for the normalization of mRNA levels. In this study, we used a systematic approach for the selection of potential reference genes in the rhesus monkey and compared their suitability to that of the corresponding genes in humans.</p> <p>Results</p> <p>Eight housekeeping genes (HKGs) (<it>GAPDH, SDHA, ACTB, RPL13A, RPL32, UBA52, PGK1Y</it>, and <it>YWHAZ</it>) from rhesus monkeys and humans were selected to test for normalization of expression levels in six different tissue types (brain, colon, kidney, liver, lung, and stomach). Their stability and suitability as reference genes were validated by <it>geNorm</it>, <it>NormFinder </it>and <it>BestKeeper </it>programs. Intriguingly, <it>RPL13A </it>and <it>RPL32 </it>were selected as ideal reference genes only in rhesus monkeys.</p> <p>Conclusion</p> <p>The results clearly indicated the necessity of using different reference genes for normalization of expression levels between rhesus monkeys and humans in various tissues.</p

Classification of rice (oryza sativa l. japonica nipponbare) immunophilins (fkbps, cyps) and expression patterns under water stress

<p>Abstract</p> <p>Background</p> <p>FK506 binding proteins (FKBPs) and cyclophilins (CYPs) are abundant and ubiquitous proteins belonging to the peptidyl-prolyl <it>cis/trans </it>isomerase (PPIase) superfamily, which regulate much of metabolism through a chaperone or an isomerization of proline residues during protein folding. They are collectively referred to as immunophilin (IMM), being present in almost all cellular organs. In particular, a number of IMMs relate to environmental stresses.</p> <p>Results</p> <p>FKBP and CYP proteins in rice (<it>Oryza sativa </it>cv. Japonica) were identified and classified, and given the appropriate name for each IMM, considering the ortholog-relation with <it>Arabidopsis </it>and <it>Chlamydomonas </it>or molecular weight of the proteins. 29 FKBP and 27 CYP genes can putatively be identified in rice; among them, a number of genes can be putatively classified as orthologs of <it>Arabidopsis </it>IMMs. However, some genes were novel, did not match with those of <it>Arabidopsis </it>and <it>Chlamydomonas</it>, and several genes were paralogs by genetic duplication. Among 56 IMMs in rice, a significant number are regulated by salt and/or desiccation stress. In addition, their expression levels responding to the water-stress have been analyzed in different tissues, and some subcellular IMMs located by means of tagging with GFP protein.</p> <p>Conclusion</p> <p>Like other green photosynthetic organisms such as <it>Arabidopsis </it>(23 FKBPs and 29 CYPs) and <it>Chlamydomonas </it>(23 FKBs and 26 CYNs), rice has the highest number of IMM genes among organisms reported so far, suggesting that the numbers relate closely to photosynthesis. Classification of the putative FKBPs and CYPs in rice provides the information about their evolutional/functional significance when comparisons are drawn with the relatively well studied genera, <it>Arabidopsis </it>and <it>Chlamydomonas</it>. In addition, many of the genes upregulated by water stress offer the possibility of manipulating the stress responses in rice.</p

Case report: A fatal case of myocardial infarction due to myocardial bridge and concomitant vasospasm: the role of stress gated SPECT

IntroductionAlthough most cases of myocardial bridge (MB) are clinically benign, sometimes it can be one of potential threats of myocardial infarction (MI) and life-threatening arrhythmia. In the present study, we present a case of ST-segment elevation MI caused by MB and concomitant vasospasm.Case PresentationA 52-year-old woman was brought to our tertiary hospital due to resuscitated cardiac arrest. Because the 12-lead electrocardiogram indicated ST-segment elevation MI, coronary angiogram was promptly commenced, which showed near-total occlusion at the middle portion of left anterior descending coronary artery (LAD). After intracoronary nitroglycerin administration, this occlusion was dramatically relieved, however, systolic compression at this site remained, indicative of myocardial bridge (MB). Intravascular ultrasound also showed eccentric compression with a “half-moon” sign, which is consistent with MB. Coronary computed tomography also showed a bridged coronary segment surrounded by myocardium at the middle portion of LAD. To assess the severity and extent of myocardial damages and ischemia, myocardial single photon emission computed tomography (SPECT) was additionally conducted, showing a moderate fixed perfusion defect around the cardiac apex, suggesting MI. After receiving optimal medical therapy, the patient's clinical symptoms and signs were improved then the patient was discharged from the hospital successfully and uneventfully.ConclusionWe demonstrated a case of MB-induced ST-segment elevation MI which was confirmed with its perfusion defects via myocardial perfusion SPECT. There have been proposed a number of diagnostic modalities to examine its anatomic and physiologic significance. Among them, myocardial perfusion SPECT can be available as one of useful modalities to evaluate the severity and extent of myocardial ischemia in patients with MB

Impact of successful restoration of sinus rhythm in patients with atrial fibrillation and acute heart failure: Results from the Korean Acute Heart Failure registry

Background: Restoring and maintaining sinus rhythm (SR) in patients with atrial fibrillation (AF) failed to show superior outcomes over rate control strategies in prior randomized trials. However, there is sparse data on their outcomes in patients with acute heart failure (AHF).Methods: From December 2010 to February 2014, 5,625 patients with AHF from 10 tertiary hospitals were enrolled in the Korean Acute Heart Failure registry, including 1,961 patients whose initial electrocardiogram showed AF. Clinical outcomes of patients who restored SR by pharmacological or electrical cardioversion (SR conversion group, n = 212) were compared to those of patients who showed a persistent AF rhythm (AF persistent group, n = 1,662).Results: All-cause mortality both in-hospital and during the follow-up (median 2.5 years) were significantly lower in the SR conversion group than in the AF persistent group after adjustment for risk factors (adjusted hazard ratio [HR]; 95% confidence interval [CI] = 0.26 [0.08–0.88], p = 0.031 and 0.59 [0.43–0.82], p = 0.002, for mortality in-hospital and during follow-up, respectively). After 1:3 propensity score matching (SR conversion group = 167, AF persistent group = 501), successful restoration of SR was associated with lower all-cause mortality (HR [95% CI] = 0.68 [0.49–0.93], p = 0.015), heart failure rehospitalization (HR [95% CI] = 0.66 [0.45–0.97], p = 0.032), and composite of death and heart failure rehospitalization (HR [95% CI] = 0.66 [0.51–0.86], p = 0.002).Conclusions: Patients with AHF and AF had significantly lower mortality in-hospital and during follow-up if rhythm treatment for AF was successful, underscoring the importance of restoring SR in patients with AHF