Radiation therapy is a highly effective local treatment for cancer. However, sporadic events of tumor regression in unirradiated fields, known as abscopal effect, have been observed for decades. This ...abscopal effect has more recently been postulated to be a result of antitumor immune response induced by radiation therapy. With the advent of modern immunotherapy, the potential for immune activation by radiation therapy defines a novel role for radiation therapy in systemic disease. In this context, we have searched documented cases abscopal effect of radiation therapy in literature. A total of 46 reported cases have been identified from 1969 to 2014 with median radiation dose of 31 Gy, median follow-up of 17.5 months, and median documented time to notice the abscopal effect was 2 months. This review systematically summarizes all clinical case reports of abscopal effect to gain insight into this uncommon but important phenomenon.
It is well known that metabolism underlies T cell differentiation and functions. The pathways regulating T cell metabolism and function are interconnected, and changes in T cell metabolic activity ...directly impact the effector functions and fate of T cells. Thus, understanding how metabolic pathways influence immune responses and ultimately affect disease progression is paramount. Epigenetic and posttranslational modification mechanisms have been found to control immune responses and metabolic reprogramming. Sirtuins are NAD
-dependent histone deacetylases that play key roles during cellular responses to a variety of stresses and have recently been reported to have potential roles in immune responses. Therefore, sirtuins are of significant interest as therapeutic targets to treat immune-related diseases and enhance antitumor immunity. This review aims to illustrate the potential roles of sirtuins in different subtypes of T cells during the adaptive immune response.
Owing to the increasing environmental and climate changes globally, there is an increasing interest in the molecular‐level understanding of environmental organic compound mixtures, that is, the ...pursuit of complete and detailed knowledge of the chemical compositions and related chemical reactions. Environmental organic molecule mixtures, including those in air, soil, rivers, and oceans, have extremely complex and heterogeneous chemical compositions. For their analyses, ultrahigh‐resolution and sub‐ppb level mass accuracy, achievable using Fourier‐transform ion cyclotron resonance mass spectrometry (FT‐ICR MS), are important. FT‐ICR MS has been successfully used to analyze complex environmental organic molecule mixtures such as natural, soil, particulate, and dissolved organic matter. Despite its success, many limitations still need to be overcome. Sample preparation, ionization, structural identification, chromatographic separation, and data interpretation are some key areas that have been the focus of numerous studies. This review describes key developments in analytical techniques in these areas to aid researchers seeking to start or continue investigations for the molecular‐level understanding of environmental organic compound mixtures.
Sirtuin 2 (SIRT2) is a member of the sirtuin protein family. It is a Class III histone deacetylase (HDACs) and predominantly localized to the cytosol. SIRT2 deacetylates histones and a number of ...non-histone proteins and plays a pivotal role in various physiologic processes. Previously, SIRT2 has been considered indispensable during carcinogenesis; however, there is now a significant controversy regarding whether SIRT2 is an oncogene or a tumor suppressor. The purpose of this review is to summarize the physiological functions of SIRT2 and its mechanisms in cancer. We will focus on five malignancies (breast cancer, non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, and glioma) to describe the current status of SIRT2 research and discuss the clinical evaluation of SIRT2 expression and the use of SIRT2 inhibitors.
Radiotherapy is a primary therapeutic modality widely utilized with curative intent. Traditionally tumor response was hypothesized to be due to high levels of cell death induced by irreparable DNA ...damage. However, the immunomodulatory aspect of radiation is now widely accepted. As such, interest into the combination of radiotherapy and immunotherapy is increasing, the synergy of which has the potential to improve tumor regression beyond that observed after either treatment alone. However, questions regarding the timing (sequential vs concurrent) and dose fractionation (hyper-, standard-, or hypo-fractionation) that result in improved anti-tumor immune responses, and thus potentially enhanced tumor inhibition, remain. Here we discuss the biological response to radiotherapy and its immunomodulatory properties before giving an overview of pre-clinical data and clinical trials concerned with answering these questions. Finally, we review published mathematical models of the impact of radiotherapy on tumor-immune interactions. Ranging from considering the impact of properties of the tumor microenvironment on the induction of anti-tumor responses, to the impact of choice of radiation site in the setting of metastatic disease, these models all have an underlying feature in common: the push towards personalized therapy.
Radiation therapy (RT) is a cornerstone in oncologic management and is employed in various curative and palliative scenarios for local-regional control. RT is thought to locally control tumor cells ...by direct physical DNA damage or indirect insults from reactive oxygen species. Therapeutic effects apart from those observed at the treatment target, that is, abscopal effect, have been observed for several decades, though the underlying mechanisms regulating this phenomenon have been unclear. Accumulating evidence now suggests that the immune system is a major determinant in regulating the abscopal effect. It is now evident that RT may also enhance immunologic responses to tumors by creating an in situ vaccine by eliciting antigen release from dying tumor cells. Harnessing the specificity and dynamic nature of the immune system to target tumors in conjunction with RT is an emerging field with much promise. To optimize this approach, it is important to systematically evaluate the intricacies of the host immune system, the new generation of immunotherapeutics and the RT approach. Here we will discuss the current biologic mechanisms thought to regulate the RT-induced abscopal effect and how these may be translated to the clinical setting.
Summary Radiotherapy has long been the mainstay of treatment for patients with head and neck cancer and has traditionally involved a stage-dependent strategy whereby all patients with the same TNM ...stage receive the same therapy. We believe there is a substantial opportunity to improve radiotherapy delivery beyond just technological and anatomical precision. In this Series paper, we explore several new ideas that could improve understanding of the phenotypic and genotypic differences that exist between patients and their tumours. We discuss how exploiting these differences and taking advantage of precision medicine tools—such as genomics, radiomics, and mathematical modelling—could open new doors to personalised radiotherapy adaptation and treatment. We propose a new treatment shift that moves away from an era of empirical dosing and fractionation to an era focused on the development of evidence to guide personalisation and biological adaptation of radiotherapy. We believe these approaches offer the potential to improve outcomes and reduce toxicity.
While STING-activating agents have shown limited efficacy in early-phase clinical trials, multiple lines of evidence suggest the importance of tumor cell-intrinsic STING function in mediating ...antitumor immune responses. Although STING signaling is impaired in human melanoma, its restoration through epigenetic reprogramming can augment its antigenicity and T cell recognition. In this study, we show that reversal of methylation silencing of STING in murine melanoma cell lines using a clinically available DNA methylation inhibitor can improve agonist-induced STING activation and type-I IFN induction, which, in tumor-bearing mice, can induce tumor regression through a CD8
T cell-dependent immune response. These findings not only provide mechanistic insight into how STING signaling dysfunction in tumor cells can contribute to impaired responses to STING agonist therapy, but also suggest that pharmacological restoration of STING signaling through epigenetic reprogramming might improve the therapeutic efficacy of STING agonists.
Cancer immune evasion is one of the hallmarks of carcinogenesis. Cancer cells employ multiple mechanisms to avoid immune recognition and suppress antitumor immune responses. Recently, accumulating ...evidence has indicated that immune-related pathways are epigenetically dysregulated in cancer. Most importantly, the epigenetic footprint of immune-related pathways is associated with the patient outcome, underscoring the crucial need to understand this process. In this review, we summarize the current evidence for epigenetic regulation of immune-related pathways in cancer and describe bioinformatics tools, informative visualization techniques, and resources to help decipher the cancer epigenome.
A State-Run Enterprise: A Bane or a Boon? KIM, Sungjune
Asian Journal of Shipping and Logistics,
September 2015, 2015-09-00, 2015-09-01, Letnik:
31, Številka:
3
Journal Article
Recenzirano
Odprti dostop
In the less than 70 years since Korean liberation, Korea has grown to be one of the world's top five ship-owning countries in 2014. This can be attributed to a few factors such as government policy, ...Korea Shipping Corporation (KSC, hereafter) and merchant marine officers. This paper will expound the true motivations of the establishment and the privatization of KSC in 1950 and in 1968, respectively. KSC, as Korea's national shipping company, sailed along a very unusual course of development. It was established in 1950 not to foster and develop Korea's shipping industry but to help alleviate the financial burdens of the fledgling Korean government. The main cause of privatizing KSC in 1968 was a purely political decision, not an economic one as it overlapped with the rapid growth period of the shipping industry in the world, as well as in Korea. In sum, KSC, a state-run enterprise, was a bane in the short run but a boon in the long run for both the Korean government and Korea's shipping industry. If we can believe KSC followed the ordinary sailing route as a state-run enterprise, we might develop a new opinion that the national shipping company might be a financial burden in a short period, but various benefits over a long period.
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