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Among the plethora of defense mechanisms which a host elicits after pathogen invasion, type 1 interferons play a central role in regulating the immune system's response. They induce several interferon-stimulated genes (ISGs) which play a diverse role once activated. Over the past few decades, there have been several studies exploring the role of ISGs in cancer and ISG15 is among the most studied for its pro and anti-tumorigenic role. In this review, we aim to provide an update on the recent observations and findings related to ISG15 in cancer. We provide a brief overview about the initial observations and important historical findings which helped scientists understand structure and function of ISG15. We aim to provide an overview of ISG15 in cancer with an emphasis on studies which delve into the molecular mechanism of ISG15 in modulating the tumor microenvironment. Further, the dysregulation of ISG15 in cancer and the molecular mechanisms associated with its pro and anti-tumor roles are discussed in respective cancer types. Finally, we discuss multiple therapeutic applications of ISG15 in current cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Cancer-related fatigue is one of the most common and persistent issues experienced by cancer patients. Cancer-related fatigue is a distinct form of fatigue that is subjective, long-lasting and unalleviated by rest or sleep. Studies have shown that almost all cancer patients experience severe fatigue that disrupts the quality of life and physical function, but cancer-related fatigue remains under-addressed in clinical care, and only about half of all patients receive treatment., Methods: To increase the awareness of cancer-related fatigue and improve current management, the Taiwan Society of Cancer Palliative Medicine and the Taiwan Oncology Nursing Society convened a consensus committee to develop recommendations for the screening, assessment and treatment of cancer-related fatigue., Results: Thirteen consensus recommendations were subsequently developed based on the best available evidence and the clinical experience of committee members., Conclusions: These recommendations are expected to facilitate the standardization of cancer-related fatigue management across Taiwan and may also serve as a reference for other clinicians., (© The Author(s) 2022. Published by Oxford University Press.)

Anti-PD-1 and oncolytic viruses (OVs) have non-overlapping anti-tumor mechanisms, since each agent works at different steps of the cancer-immunity cycle. Evidence suggests that OVs improve therapeutic responses to anti-PD-1 therapy by reversing immunosuppressive factors, increasing the number and diversity of infiltrating lymphocytes, and promoting PD-L1 expression in both injected and non-injected tumors. Many studies in preclinical models suggest that the timing of anti-PD-1 administration influences the therapeutic success of the combination therapy (anti-PD-1 + OV). Therefore, determining the appropriate sequencing of agents is of critical importance to designing a rationale OV-based combinational clinical trial. Currently, the combination of anti-PD-1 and OVs are being delivered using various schedules, and we have classified the timing of administration of anti-PD-1 and OVs into five categories: (i) anti-PD-1 lead-in → OV; (ii) concurrent administration; (iii) OV lead-in → anti-PD-1; (iv) concurrent therapy lead-in → anti-PD-1; and (v) OV lead-in → concurrent therapy. Based on the reported preclinical and clinical literature, the most promising treatment strategy to date is hypothesized to be OV lead-in → concurrent therapy. In the OV lead-in → concurrent therapy approach, initial OV treatment results in T cell priming and infiltration into tumors and an immunologically hot tumor microenvironment (TME), which can be counterbalanced by engagement of PD-L1 to PD-1 receptor on immune cells, leading to T cell exhaustion. Therefore, after initial OV therapy, concurrent use of both OV and anti-PD-1 is critical through which OV maintains T cell priming and an immunologically hot TME, whereas PD-1 blockade helps to overcome PD-L1/PD-1-mediated T cell exhaustion. It is important to note that the hypothetical conclusion drawn in this review is based on thorough literature review on current understanding of OV + anti-PD-1 combination therapies and rhythm of treatment-induced cancer-immunity cycle. A variety of confounding factors such as tumor types, OV types, presence or absence of cytokine transgenes carried by an OV, timing of treatment initiation, varying dosages and treatment frequencies/duration of OV and anti-PD-1, etc. may affect the validity of our conclusion that will need to be further examined by future research (such as side-by-side comparative studies using all five treatment schedules in a given tumor model)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Oncolytic viruses (OVs), such as the oncolytic herpes simplex virus (oHSV), are a rapidly growing treatment strategy in the field of cancer immunotherapy. OVs, including oHSV, selectively replicate in and kill cancer cells (sparing healthy/normal cells) while inducing anti-tumor immunity. Because of these unique properties, oHSV-based treatment strategies are being increasingly used for the treatment of cancer, preclinically and clinically, including FDA-approved talimogene laherparevec (T-Vec). Growth, purification, and titration are three essential laboratory techniques for any OVs, including oHSVs, before they can be utilized for experimental studies. This paper describes a simple step-by-step method to amplify oHSV in Vero cells. As oHSVs multiply, they produce a cytopathic effect (CPE) in Vero cells. Once 90-100% of the infected cells show a CPE, they are gently harvested, treated with benzonase and magnesium chloride (MgCl2), filtered, and subjected to purification using the sucrose-gradient method. Following purification, the number of infectious oHSV (designated as plaque-forming units or PFUs) is determined by a "plaque assay" in Vero cells. The protocol described herein can be used to prepare high-titer oHSV stock for in vitro studies in cell culture and in vivo animal experiments.

Oncolytic viruses (OVs) are genetically modified or naturally occurring viruses, which preferentially replicate in and kill cancer cells while sparing healthy cells, and induce anti-tumor immunity. OV-induced tumor immunity can be enhanced through viral expression of anti-tumor cytokines such as interleukin 12 (IL-12). IL-12 is a potent anti-cancer agent that promotes T-helper 1 (Th1) differentiation, facilitates T-cell-mediated killing of cancer cells, and inhibits tumor angiogenesis. Despite success in preclinical models, systemic IL-12 therapy is associated with significant toxicity in humans. Therefore, to utilize the therapeutic potential of IL-12 in OV-based cancer therapy, 25 different IL-12 expressing OVs (OV-IL12s) have been genetically engineered for local IL-12 production and tested preclinically in various cancer models. Among OV-IL12s, oncolytic herpes simplex virus encoding IL-12 (OHSV-IL12) is the furthest along in the clinic. IL-12 expression locally in the tumors avoids systemic toxicity while inducing an efficient anti-tumor immunity and synergizes with anti-angiogenic drugs or immunomodulators without compromising safety. Despite the rapidly rising interest, there are no current reviews on OV-IL12s that exploit their potential efficacy and safety to translate into human subjects. In this article, we will discuss safety, tumor-specificity, and anti-tumor immune/anti-angiogenic effects of OHSV-IL12 as mono- and combination-therapies. In addition to OHSV-IL12 viruses, we will also review other IL-12-expressing OVs and their application in cancer therapy., Competing Interests: The authors declare no conflict of interest. The funders had no role in the writing of the manuscript or in the decision to publish the manuscript.

Background & Problems: The return-to-treatment rate is an important indicator of treatment outcome and care effectiveness in cancer patients. The return-to-treatment rates for patients at National Taiwan University Hospital (NTUH) in 2011 and 2012 were 38.5% and 33.3%, respectively. In order to improve the quality of care that is provided to patients, we reviewed NTUH's current clinical case management protocols for handling patients who refused treatment and then identified and resolved the potential problems in these protocols., Purpose: To raise the return-to-treatment rate above 45% by 2013., Resolution: We developed four new interventions to improve the return-to-treatment rate. Firstly, we assembled a quality care team that monitored the rates of patient return to treatment on a monthly basis and reminded case managers to follow up with patients regularly. Secondly, we introduced new protocols for case managers that facilitated the ongoing analysis of the reasons that patients elect not to return to treatment. Thirdly, we delivered regular education programs for case managers addressing good quality and quantity care for cancer patients. Finally, we developed an interdisciplinary liaison care program for patients., Results: After implementing these four interventions, the return-to-treatment rate improved to 48% in 2013., Conclusions: This improvement project demonstrated that integrating an interdisciplinary team, assembling a quality care team, implementing new protocols to help cancer patients who refuse to commence / continue treatment, providing regular education to clinical case managers, and enacting an interdisciplinary care program were all helpful to improving the effectiveness of cancer care services and the return-to-treatment rate of cancer patients.

Nurses play a crucial role in cancer pain control, but little is known about how well-prepared nurses are to manage cancer pain in Taiwan. The purpose of this study was to examine the level of knowledge about pain management among Taiwanese nurses with different background characteristics and to determine the predictor(s) of nurses' pain management knowledge. Nurse subjects were recruited by a cross-sectional nationwide survey with stratified sampling from nine hospitals distributed in the four major geographic regions of Taiwan. The Nurses' Knowledge and Attitudes Survey-Taiwanese version (NKAS-T) and a background information form were used to collect the data. Of 1900 surveys distributed, 1797 valid questionnaires (94.5%) were analyzed. The average correct response rate was 50.5%, with rates ranging from 7-86% for each survey question. Results from stepwise regression showed that nurses with higher mean correct answer scores had BS or higher degrees, had received pain education at professional conferences, had more prior hours of pain education, had longer clinical care experiences, and always worked with cancer patients. Nurses who worked in intensive care units, however, had significantly lower mean correct scores. The results strongly suggest an urgent need to strengthen pain education in Taiwan. The results also provide the direction for developing pain education.